Bugs and Drugs Handbook 2020 - Children's Hospital Colorado

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Bugs and Drugs Handbook 2020 - Children's Hospital Colorado
Bugs and Drugs Handbook
          2020

 Amelia Velasquez
 Age 9
Bugs and Drugs Handbook 2020 - Children's Hospital Colorado
Bugs and Drugs Handbook 2020 - Children's Hospital Colorado
Table of Contents
                                                                                                                                                        Page

How to Improve Infectious Disease Outcomes and Reduce Costs- Sutton’s
Law: “Culture Where the Infection Is!”.................................................................................................                     1

Legend for Antimicrobial Tables ............................................................................................................                2

Antibiogram Table 1 - Staphylococci ......................................................................................................                  3

Antibiogram Table 2A and 2B - Streptococci ........................................................................................ 4-5

Antibiogram Table 3 – Gram Negative Organisms Non-Urine ............................................................                                        6

Antibiogram Table 4 – Gram Negative Organisms Urine ....................................................................                                    7

Antibiogram Table 5 – Gram Negative Orgs Non-Enterobacteriaceae...............................................                                              8

Antibiogram Table 6 – Candida spp .......................................................................................................                   9

Antibiogram Table 7 – Anaerobes........................................................................................................... 10

Microbiology Testing Schedule................................................................................................................ 11

Multiplex PCR Information .....................................................................................................................12-14

Culture Collection and Testing Information ..........................................................................................14-18

Critical and Urgent Value Reporting Policy for Microbiology ............................................................ 18

Blood Isolates............................................................................................................................................. 19

MRSA and VRE Rates .............................................................................................................................20-21

Influenza Virus Treatment and Antiviral Medications Recommended ..............................................22-24

Guidelines for Changing from IV to PO Antibiotics in Hospitalized Children ..................................25-26

Antimicrobial Formulary at Children’s Hospital Colorado .................................................................27-38

Collection Guidelines for Antimicrobial Levels .....................................................................................39-42
Bugs and Drugs Authorship
For additional copies of this publication, please call the Microbiology Laboratory at 720-777-6703, download a
copy from My Children’s Colorado website or request an electronic copy from Elaine Dowell or Stacey
Hamilton.

Thanks to the following contributors to this booklet:

Sam Dominguez, MD, PhD
Medical Director, Clinical Microbiology Laboratory
Associate Medical Director, Infection Prevention and Control
Sarah Parker, MD
Professor of Pediatric Infectious Diseases
Medical Director of Antimicrobial Stewardship

Sarah Jung, PhD, D(ABMM)
Assistant Director of Microbiology

Elaine Dowell, MT(ASCP)SM
Senior Manager Microbiology and Precision Diagnostics
elaine.dowell@childrenscolorado.org

Stacey Hamilton, MT(ASCP)SM
Microbiology Manager
stacey.hamilton@childrenscolorado.org

Kristin Pretty, M(ASCP)MB
Supervisor Virology/Molecular Microbiology

Jason Child, PharmD, BCIDP
Infectious Disease Pharmacist
Christine MacBrayne, PharmD, MSCS, BCIDP
Infectious Disease Pharmacist

Ann-Christine Nyquist, MD, MSPH
Medical Director, Infection Prevention and Control

                                           © Children's Hospital Colorado
How to Improve Infectious Disease Outcomes and Reduce Costs

            Sutton’s Law: Culture Where the Infection Is!

Key Principles for Culturing and Antimicrobial Use:
   1. “Garbage In, Garbage Out” – Don’t order cultures if you won’t know
      how to interpret the result. This often applies to surface (skin, mucous
      membranes) cultures that are always colonized with normal flora.
   2. “Tissue is the Issue” Don’t use swabs; get a tissue biopsy or needle
      aspirate. Bacteria are absorbed into and die on swabs.
   3. Sutton’s Law: “Culture where the infection is” – Blood cultures will only
      be positive
2019 Annual Antibiogram
                         Tables 1 – 8
                Legend for Antibiogram Tables

     Indicates first-line therapy, with susceptibility between 75-100%. This medication
     has good penetration, limited side-effects and overall strong susceptibilities.

     Second-line. Susceptibility between 75-100%, but not first choice due to overly
     broad-spectrum, toxicities, or both. May be appropriate as initial therapy before
     specific bacteria has been identified.

     Susceptibility between 50-74%. Not initial treatment of choice, but can be used if
     other medications are not available, patient has significant allergies, or
     susceptibility known.

     Susceptibility for these medications is less than 50%. Consult ID prior to using
     these medications and/or use only if known susceptible.

-    Not tested.

R    This organism is known to have intrinsic resistance to this antibiotic.

     This organism is known to be susceptible to this antibiotic.
S

     Small number of organisms used for data collection.
()
      Color scheme adapted from the Sanford Guide to Antimicrobial Therapy

                                       2
TABLE 1. Gram Positive Organisms: Staphylococcus (% Susceptible)
            Antimicrobial Susceptibilities at Children’s Hospital Colorado – 2019

                                                                      ANTIMICROBIALS

                               NUMBER OF ISOLATES

                                                                                Trimethoprim / Sulfa
       ORGANISMS

                                                    Vancomycin

                                                                 Clindamycin

                                                                                                       Oxacillin*
                               TESTED

Staph aureus (MSSA)                    574          100           84              99                   100
Staph aureus (MRSA)                    230          100           83              99                      R
Staph epidermidis                      101          100               -        74                       30
Staph hominis                            32         100               -           84                    41
Testing by Microscan Microtiter Panel.

* Includes agents: Nafcillin/Dicloxacillin/Methicillin. If susceptible, also susceptible to
cefazolin/cephalexin and beta lactam + beta lactamase combinations. If susceptible, this does
not infer susceptibility to clindamycin; please see specific clindamycin results.

Oxacillin resistance in Staphylococcus spp. predicts resistance to ALL beta-lactams including
penicillins, carbapenems, β-lactam/β-lactamase inhibitor combinations, cephems (except for
cephalosporins with anti-MRSA activity, namely ceftaroline).

Confirmation of MRSA is done by PBP2, Cefoxitin Screen or Microscan Panel.

Cefoxitin is tested as a surrogate for oxacillin. Oxacillin susceptible or resistant is based on the
Cefoxitin Screen result.

Clindamycin susceptibility is not determined by Cefoxitin Screen or oxacillin resistance.

The Inducible Clindamycin Test detects inducible clindamycin resistance, due to the erm genes.
The isolate is presumed resistant to clindamycin when the Inducible Clindamycin Test is positive.

                                                       3
TABLE 2A. Gram Positive Organisms - Streptococcus and Enterococcus
                                             (% Susceptible)
                  Antimicrobial Susceptibilities at Children’s Hospital Colorado – 2019
                                                                           ANTIMICROBIALS

                                                       NUMBER OF
                                                        ISOLATES

                                                                                                            Clindamycin
                                                                                               Vancomycin
                                                                                 Amoxicillin

                                                                                                                          Ceftriaxone
                                                                                 Ampicillin/
                                                                   Penicillin^
                       ORGANISMS

Strep. anginosus Group1 – Invasive* ,+                   32                96       -          100              81            97
Strep. mitis1 * , ++                                     49                49       -          100              94            90
Viridans Strep Group1 * ,+++                             96                73       -          100              89            94
Beta Strep Group A1 – Invasive                           32                 S       S            S              97             S
Beta Strep Group B 1                                     61                 S       S            S              67             S
Beta Strep Group B 1 (prenatal screens)                 568                 S       S          100              54             S
Enterococcus faecalis2                                  115                 -     100          100               -             -
Enterococcus faecium 2                                  (24)                -      71           96               -             -
1 Testing   is by Sensititre microtiter panel. 2Testing is by Microscan microtiter panel.

Streptococci:
The Inducible Clindamycin Test (D-test) detects inducible clindamycin resistance due to the erm gene.
For streptococci, resistance to clindamycin is presumed when the D-Test is positive.
* Most penicillin non-susceptible streptococci that fall into the intermediate MIC
  range (0.25 to 2 µg/mL) can be treated with high dose ampicillin/amoxicillin.
+ Of the penicillin non-susceptible S. anginosus isolates tested, 2% were intermediate and

  2% were resistant.
++ Of the penicillin non-susceptible Strep. mitis group isolates tested, 43% were intermediate and 8%

  were resistant.
+++ Of the penicillin non-susceptible viridans streptococci tested, 22% were intermediate and 5%

  were resistant.
^ Streptococci susceptible to penicillin are also susceptible to ampicillin/amoxicillin.

Enterococci
Combination therapy should be used in serious Enterococcus spp. Infection (endocarditis & bacteremia).
Gentamicin Synergy Screen – E. faecalis = 90% susceptible
Gentamicin Synergy Screen – E. faecium = 88% susceptible
Isolates that are susceptible to ampicillin cannot be assumed to be susceptible to penicillin.
One new VRE patient was identified in 2019. For therapy choices, ID consult recommended.

                                                        4
TABLE 2B. Gram Positive Organisms: Streptococcus pneumoniae (% Susceptible)
               Antimicrobial Susceptibilities at Children’s Hospital Colorado - 2019
                                                                                                                                                            ANTIMICROBIALS

                                                    (Nonmeningitis breakpoint)

                                                                                                                                       (Nonmeningitis breakpoint)

                                                                                                                                                                                                                          Trimethoprim/Sulfa
                 Number of isolates

                                                                                               (Meningitis breakpoint)

                                                                                                                                                                                  (Meningitis breakpoint)
    Source

                                                                                                                                                                                                                                               Vancomycin
                                                                                                                                                                                                            Clindamycin
                                                                                                                         Ceftriaxone

                                                                                                                                                                    Ceftriaxone
                                      Penicillin^

                                                                                 Penicillin^

CSF*            (12)                            NA                                  92                                      NA                                       100                                      -              -                 100
Blood or
Sterile               36                      100                                   64                                    100                                          94                                   92            78                   100
Aspirate
Respiratory
and             127                             97                                  61                                      98                                         82                                   87            78                   100
Other
Testing is by Sensititre microtiter panel.

   Patients with pneumococcal meningitis should be started on vancomycin and ceftriaxone until
    susceptibilities are available. Isolates were recovered in 2017, 2018 and 2019.

 Refer to organism specific susceptibility. Isolates in the intermediate category to penicillin may be
  treated with high dose ampicillin/amoxicillin unless in the CNS.

S. pneumoniae isolates that are susceptible to penicillin are also susceptible to ampicillin (and amoxicillin
if oral choice is appropriate).

Ceftriaxone susceptibility does not imply susceptibility to oral cephalosporins.

                                                                                                                                       5
TABLE 3. Gram Negative Organisms, Non-Urine (% Susceptible)
                        Antimicrobial Susceptibilities at Children’s Hospital Colorado – 2019
                                                                                                                  ANTIMICROBIALS

                                                                       Ampicillin / Amoxicillin
                                                  NUMBER OF ISOLATES

                                                                                                                                                Trimethoprim / Sulfa
                    ORGANISMS

                                                                                                                   Cefotaxime **

                                                                                                                                                                       Ciprofloxacin
                                                                                                                                   Gentamicin
                                                                                                      Cefazolin
                                                                       No further testing is routinely performed for beta-
      Haemophilus influenzae1*
                                                    80                  lactamase negative isolates. These isolates are
      Beta-lactamase testing - all isolates
                                                                               considered ampicillin susceptible.
      Haemophilus influenzae1*                      37                      30                          -          100               -               -                    -
      Escherichia coli2                             96                      41                         81           88              90              68                   81
      Enterobacter cloacae complex2                 39                      R                          R           IB^             100              97                   97
      Klebsiella pneumoniae2                        42                           R                     88            98              98             90                 100
     Klebsiella oxytoca2                         (26)                    R                             54          100              96           92                      96
     Serratia marcescens 2                       (11)                    R                             R           IB^             100          100                      91
SalmSalmonella species2                           46                    76                              -           96               -           87                       -
     Shigella species2,***                        47                    573                             -           98               -           47                       -
      1
          Tested by Sensititre microtiter panel. 2Tested by Microscan microtiter panel. 3Tested by disk diffusion.

       Haemophilus influenzae isolates that test positive for beta-lactamase production are still considered
        susceptible to ampicillin-sulbactam or amoxicillin-clavulanic acid.

      **Cefotaxime susceptible isolates are also ceftriaxone susceptible.

      ***Isolates were recovered in 2017, 2018 and 2019.

       When IB is indicated above, the organism may have an inducible beta-lactamase. Although the MIC may
            indicate susceptibility, beta-lactams should only be used in combination with a drug from another class to
            which the organism is susceptible. Cefepime and meropenem are exceptions and may be used alone.

                                                                                                  6
TABLE 4. Gram Negative Organisms Isolated from Urine (% Susceptible)

                       Antimicrobial Susceptibilities at Children’s Hospital Colorado – 2019+

                                                                                                                               ANTIMICROBIALS

                                                 Ampicillin / Amoxicillin
                            NUMBER OF ISOLATES

                                                                            Ampicillin/Sulbactam

                                                                                                                                                                             Trimethoprim / sulfa
       ORGANISMS

                                                                                                                                                            Nitrofurantoin
                                                                                                                               Cefotaxime **
                                                                                                   Cephalothin*

                                                                                                                                                                                                    Ciprofloxacin

                                                                                                                                                                                                                               Ceftazidime
                                                                                                                                               Gentamicin
                                                                                                                  Cefuroxime

                                                                                                                                                                                                                    Cefepime
E. coli              1366                        63                                  56            68             94           95              92           98               74                     90                 96              -
Enterobacter cloacae
                      43                              R                                  R           R                R        IB^             95           33               84                     98              98                 -
complex
Klebsiella
                     106                              R                              75            78             89           94              88           52               80                     88                 96              -
pneumoniae
Klebsiella oxytoca    43                         R                                   63            67             81           100             100          98               93                     95               100               -
Proteus mirabilis     72                         90                                  96            99             99            99              96          R                85                     94               100               -
Citrobacter freundii
                     (21)                             R                                  R           R                R        IB^             86           86               81                     86              100                -
complex
Pseudomonas
                      44                              R                                  R           R                R          R             89             R                 R                   89                 95           98
aeruginosa
Testing by Microscan microtiter panel.

+   Breakpoints used for interpretations have been established by the FDA and may not be consistent with current
    CLSI guidelines. Isolates that test resistant may respond to high levels of antimicrobials present in urine.

 Cephalothin results are a surrogate to predict susceptibility to the oral cephalosporin agents: cephalexin,
  cefuroxime, cefpodoxime, and cefdinir. Notably for lower tract infection, low level resistance can often be
  overcome by high-end dosages due to high concentrations of these agents in the urine.

**Isolates that are susceptible to cefotaxime are also susceptible to ceftriaxone.

 When IB is indicated above, the organism may have an inducible beta-lactamase. Although the MIC may
     indicate susceptibility, beta-lactams should only be used in combination with a drug from another class to
     which the organism is susceptible. Cefepime and meropenem are exceptions and may be used alone.

                                                                                                                  7
TABLE 5. Non-Enterobacteriaceae (% Susceptible)
                     Antimicrobial Susceptibilities at Children’s Hospital Colorado– 2019
                                                                                                               ANTIMICROBIALS

                                 NUMBER OF ISOLATES

                                                                                                               Trimethoprim / Sulfa
        ORGANISMS

                                                                                                                                                                              Pip/Tazobactam
                                                                                                                                      Ciprofloxacin

                                                                                                                                                                                                              Meropenem
                                                                                                                                                                                               Levofloxacin
                                                                                                 Minocycline
                                                      Ceftazidime

                                                                                Tobramycin

                                                                                                                                                      Gentamicin
                                                                    Aztreonam

                                                                                                                                                                   Cefepime
Pseudomonas
aeruginosa
 • Non CF1                      96                    94            86             -               -                  -               93              76           90         97                   -               -
 • CF-mucoid2,3                 38                    79            68          66                 -                  -               58                 -           -             -               -           80
    • CF-nonmucoid2,3           63                    82            68          73                 -                  -               67                 -           -             -               -           43
Stenotrophomonas
                                32                    12               -           -             90            72                         -              -           -              -          59                  -
maltophilia2,3
1   Non-CF testing performed by Microscan microtiter panel.
2   Cystic fibrosis (CF) Pseudomonas spp. isolates and S. maltophilia isolates tested by E-test.
3
    Isolates recovered in 2017, 2018 and 2019 were included in this data.

                                                                                             8
TABLE 6. Candida species (% Susceptible)
        Antimicrobial Susceptibilities at Children’s Hospital Colorado– 2019
                                                                                              ANTIFUNGALS

                                NUMBER OF ISOLATES
      ORGANISMS

                                                                     Amphotericin

                                                                                                                                Posaconazole
                                                     5-Flucytosine

                                                                                                                                               Voriconazole
                                                                                                    Itraconazole
                                                                                      Fluconazole

                                                                                                                   Micafungin
Candida albicans               (21)                  NI              NI              100            NI              100         NI             100
Candida parapsilosis           (19)                  NI              NI              100            NI              100         NI             100
Candida glabrata               (13)                  NI              NI             (SDD)*          NI                85        NI             NI
Candida lusitaniae             (7)                   NI              NI               NI            NI                 NI       NI             NI
Testing performed at University of Colorado Microbiology lab by microbroth dilution
Isolates recovered in 2017, 2018 and 2019 were included in this table.

NI – No interpretative criteria available

   SDD - Susceptible Dose Dependent
     The susceptible dose dependent category implies that susceptibility of an isolate is
      dependent upon the dosing regimen that is used in the patient. It is necessary to
      use a dosing regimen (higher doses, more frequent doses or both) that results in
      high drug exposure. ID consult recommended.

Please Note: C. krusei is intrinsically resistant to fluconazole (isolates not tested).
Yeast susceptibilities were performed from the following sources:
    CSF/Shunt/Blood – 16
    Sterile Aspirate/Tissue - 10
    Stool – 2
    Miscellaneous/Wound – 12
    Urine – 8
    Respiratory –5
    Vaginal - 2

                                                                     9
Table 7. Cumulative Antimicrobial Susceptibility Report for Anaerobic Organisms

ANAEROBIC ORGANISMS
                                                                                                           Isolates Collected from Selected US hospitals Jan 2013 through December 2016
   ANTIMICROBIALS

                                                       Ampicillin-sulbactam (Unasyn®)

                                                                                                                        Piperacillin/tazobactam

                                                                                                                                                      Number of Isolates
                           Number of Isolates

                                                                                                 Number of Isolates

                                                                                                                                                                                                                                              Number of Isolates

                                                                                                                                                                                                                                                                                          Number of Isolates

                                                                                                                                                                                                                                                                                                                                   Number of Isolates
                                                                                                                                                                                                  Number of Isolates

                                                                                                                                                                                                                                                                                                                                                             Metronidazole
                                                                                                                                                                                                                                                                                                                Clindamycin
                                                                                                                                                                                                                            Meropenem
                                                                                                                                                                                Cefoxitin

                                                                                                                                                                                                                                                                        Penicillin
Percent Susceptible (%S)                                                                                                (Zosyn®)
                                                 %                                        %                            %                          %                        %                %                          %                %              %                             %             %           %              %                         %                    %

                                                                                                                                                                                                                                                                                                                                                                                   10
and Percent Resistant
                                                 S                                        R                            S                          R                        S                R                          S                R              S                             R             S           S              R                         S                    R
(%R)
Breakpoints ug/ml                               32/16                        128/4                          64                        16                        2                        8                         32
B. fragilis                129                   84                                       2      1030                  96                    1          830                100               0    1505                 93                5                -          -                -   1013                 26             22    1140                100                   0
Fusobacterium
                           (20)                 100                                       0            55              96                         2               -         -                -      (20)               100               0                -         -                -          75             77             21            75          95                    5
nucleatum- necrophorum

Anaerobic Gram- positive
                                  -              -                                        -      1853                  99                         1               -         -                -    1647                 100               0    1647                 100               0    1826                 97             3     1692                100                   0
cocci

Cutibacterium acnes
                                  -              -                                        -        (18)               100                         0               -         -                -                -         -                -                -         -                -      (17)               53             35        (18)             0                   100
(formerly P. acnes)

Data adapted from CLSI M100-S28 January 2019.
Data was generated from unique isolates from patient specimens submitted to selected US hospitals.
() Data collected from fewer than the CLSI documented M39 recommendation of 30 isolates.
Microbiology Testing Schedule

                                 Microbiology
CSF Gram Stain                                    45 minutes
Blood Culture                                     5 days to final negative
BCID on positive blood or broth culture           3 hours
Strep Only Culture                                1 day to prelim, 48 hours
                                                  to final
Tissue or Aspirate Bacterial Culture              5-7 days to final negative
Urine Culture, Clean Catch                        24 hours to final report
Urine Culture, Catheter                           48 hours to final negative
Fungus Culture                                    4 weeks to final negative
Mycobacterial Culture                             6 weeks to final negative
                     On-Demand Molecular Microbiology
C. trachomatis (CT)/N. gonorrheae (NG) PCR        24 hours
C. difficile PCR                                  3 hours
Gastrointestinal Pathogen Panel                   3 hours
Influenza A and B PCR                             3 hours (flu season only)
Meningitis/Encephalitis Pathogen PCR              3-5 hours
MRSA/SA PCR for NP Swabs                          3 hours
MRSA/SA PCR SSTI for Musculoskeletal Specimens 3 hours
Respiratory Pathogen PCR                          3 hours
Trichomonas spp. PCR                              3 hours
                   Molecular Microbiology Batch Testing
Adenovirus PCR            Monday, Wednesday and Thursday
CMV PCR                   Daily Monday -Friday
EBV PCR                   Daily Monday - Friday
Enterovirus PCR           CSF 3 hours
                          All other sources batched once daily
HHV-6 PCR                 Monday, Wednesday and Thursday
HSV and VZV PCR           Daily 7 days a week
Kingella PCR              Daily (performed when MRSA/SAU neg,
Multiplex PCR Panel Information
MEP (Meningitis/Encephalitis Pathogen Panel)
The Meningitis/Encephalitis Pathogen Panel tests for 14 pathogens associated with
meningitis/encephalitis. Testing is orderable in Epic for CSF by one of two avenues:
-Automatic MEP: CSF will be tested regardless of CSF cell count. Order is recommended if the
patient meets one of these criteria: patient is less than 2 months of age, patient has been diagnosed with
encephalitis, patient is immunocompromised, or test is approved by Infectious Disease or Neurology.
-Conditional MEP: CSF will only be tested if the CSF white cell count is greater or equal to 5. Order
is recommended for all patients not meeting the above requirements for automatic MEP.

Bacteria                                  Viruses                             Yeast
Escherichia coli                          Cytomegalovirus                     Cryptococcus neoformans
Haemophilus influenzae                    Enterovirus
Listeria monocytogenes                    Herpes simplex virus 1, 2*
Neisseria meningitidis                    HHV6 DNA detected
Streptococcus agalactiae                  Parechovirus
Streptococcus pneumoniae                  Varicella-zoster virus

Positive results for any bacteria, Cryptococcus, HSV 1/2 or VZV are reported directly to the provider.
Positive results for CMV, enterovirus, HHV-6 or parechovirus are reported to Antimicrobial
Stewardship from 8am-5pm Monday-Friday and they relay the report to the clinician. On weekends,
holidays and outside of regular hours, the report is phoned directly to the clinician. Samples from
Network of Care (NOC) are sent to Children’s Anschutz Campus for processing.
*HSV PCR may be initially negative when sampling is performed early in disease course. Consider a
repeat spinal tap and HSV PCR if clinically indicated. When ordering MEP, do not order any single-
plex PCR (HSV PCR, ENTV PCR) on the same sample.

GIP (Gastrointestinal Pathogen Panel) with or without C. difficile Testing
The Gastrointestinal Pathogen Panel tests for 17 pathogens associated with infectious gastroenteritis.
The GIP can be ordered with or without C. difficile. Stool testing should not be performed on patients
who are receiving laxatives or who do not have evidence of diarrhea (> 3 Bristol scale= 6 or 7 stools in
24 hours). Positive GIP results for C. difficile are not reported on stools from children under a year of
age. Consider ordering Clostridium difficile PCR instead of GIP if C.difficile is the only clinical
concern in patients of any age. Samples from Network of Care (NOC) are sent to Children’s Anschutz
Campus for processing.

Bacteria                                  Parasites                           Viruses
Campylobacter species                     Cryptosporidium species             Adenovirus type 40/41
Clostridium difficile toxin               Cyclospora cayetanesis              Astrovirus
Plesiomonas shigelloides                  Entamoeba histolytica/dispar        Norovirus
Salmonella species                        Giardia lamblia                     Rotavirus
Yersinia enterocolitica grp.                                                  Sapovirus
E.coli Shiga-like toxin Positive
E.coli 0157
Shigella species
Susceptibilities are performed and reported for Salmonella spp. and Shigella spp.
                                                    12
RPP (Respiratory Pathogen Panel)
The Respiratory Pathogen Panel tests for 17 pathogens associated with infectious respiratory illness.
Samples from Network of Care are sent to Children’s Anschutz Campus for processing.

Viruses                                                                Bacteria
Rhinovirus/Enterovirus               Parainfluenza 1-4                 Mycoplasma pneumoniae
Human Metapneumovirus                RSV                               Chlamydophila pneumoniae
Adenovirus                                                             Bordetella pertussis*
Influenza A (and H1 and H3 subtypes)
Influenza B (both clades detected)
Coronaviruses (HKU1, NL63, OC43, 229E)

* If concerned about pertussis, order Bordetella pertussis and Bordetella parapertussis specific PCR
tests.

BCID (Blood Culture Identification Panel)
The BCID panel tests for 24 pathogens and 3 antibiotic resistance genes associated with bloodstream
infections and is run automatically on all initial positive blood cultures.

Gram Positive Bacteria             Gram Negative Bacteria                      Yeast
Enterococcus spp.                  Acinetobacter baumannii                     Candida albicans
Listeria monocytogenes             Haemophilus influenzae                      Candida glabrata
Staphylococcus spp.                Neisseria meningitidis                      Candida krusei
Staphylococcus aureus              Pseudomonas aeruginosa                      Candida parapsilosis
Streptococcus spp.                 Enterobacteriaceae (Enteric bacteria)       Candida tropicalis
Streptococcus agalactiae           Enterobacter cloacae complex
Streptococcus pyogenes             Esherichia coli
Streptococcus pneumoniae           Klebsiella oxytoca
                                   Klebsiella pneumoniae
                                   Serratia marcescens

Antibiotic Resistance Genes, if positive resistance is present:
mecA – methicillin resistance
vanA/B – vancomycin resistance associated with VRE
KPC – one type of carbapenem resistance associated with high level resistance in gram negatives
Positive results are reported directly to Antimicrobial Stewardship from 8am-5pm, Monday-Friday and
they relay the report to the clinician. On weekends, holidays and outside regular hours, the report is
phoned directly to the clinician.

BCID is performed on positive broth cultures from sterile site aspirates and tissues .
Same panel that is run on positive blood cultures is also run on positive broth culture from sterile sites.
Testing is performed on the first initial positive broth culture.

                                                    13
MSK (Musculoskeletal) PCR Panel
The MSK PCR Panel can be run on bone tissue, bone aspirate, synovial fluid, synovial tissue, and other
deep MSK aspirates from patients with suspicion for infection. Once regular microbiologic testing
(cultures) is processed samples will undergo the Cepheid MRSA/SA SSTI PCR assay which will detect
the presence of SA and MRSA (performed 7 days a week, 24 hours a day, with a 3-hour turnaround
time). If that is negative, for children < 5 years old, Kingella kingae PCR will be performed with
results available 2 pm the following day (Mon-Fri).

                           Culture Collection and Testing Information

Blood Cultures
If antibiotics will be started or changed, CHCO policy recommends collection of two blood cultures in
advance. Separately prepare the IV caps when drawing from a central line. Place each blood specimen
into a separate blood culture bottle. When followed correctly, this practice provides a better
interpretation, as organisms detected in one of two cultures are likely to be a normal skin flora
contaminant.

Select the type of bottle type based on the volume of blood to be drawn from the patient (Table 1).
Collect at least 1 mL of blood with at an additional 1 mL of blood for each year of age to a maximum
of 10 mL. Volumes of blood less than 1 mL are generally insufficient for the accurate exclusion of
bacteremia. Although we never reject a blood culture, the volume of blood is critical (more is better).
If collecting blood from patients with suspected endocarditis, 3 large volume blood cultures are best, up
to 10mL each.

                             Table 1: Blood Culture Quantities by Age
                                    Minimum (mL)
                                                        Blood Culture Bottle
                        Age         Per Each Blood
                                                                 Type
                                         Culture
                 0y (less than 1 y) 1 mL             (Pink) BD Bactec Peds Plus
                 1y                 2 mL             (Pink) BD Bactec Peds Plus
                 2y                 3 mL             (Pink) BD Bactec Peds Plus
                 3y                 4 mL             (Blue) BD Bactec Plus
                 etc.               etc.             (Blue) BD Bactec Plus
                 9 y and older      10 mL            (Blue) BD Bactec Plus

Anaerobic blood cultures are infrequently utilized in pediatric patients due to the rare incidence of
anaerobic bacteremia in our population. In cases of suspected Lemierre’s disease or bacteremia due to
deep wound infection or abscess, request an anaerobic blood culture bottle from the Microbiology
Laboratory.

Single isolates: Susceptibility testing is automatically performed on clinically significant isolates on all
patients from all sites. Isolates that are known contaminates from peripheral draws will have
susceptibilities performed only upon clinician request. The exception is Bone Marrow Transplant and
Hematology/Oncology patients. Susceptibilities are performed on these patients on all isolates from
any source.

                                                     14
Multiple isolates recovered in succession: Susceptibility testing is performed automatically on the first
two isolates from blood and CSF cultures. Susceptibilities are repeated on isolates obtained from
positive cultures collected 4 days or more after the initial susceptibility test. The first three isolates are
frozen for future reference.

Culture Results
Check the computer for culture status and updated reports. If results are pending, the culture has not
been read or does not meet the criteria for a negative report (i.e. not incubated long enough). Most
negative reports are not issued before 18-24 hours. Network of Care Urgent Values are reported by
Epic Inbox.

C. trachomatis, N. gonorrhoeae and Trichomonas vaginalis PCR
Urine for C. trachomatis and N. gonorrhoeae PCR should be from the first part of the stream without
self-cleaning. Patient should not have urinated in the previous hour before collection. Clean
catch/midstream urines are acceptable when submitting for both urine culture and CT NG PCR.

CSF Cultures
Bacterial culture is performed on the first tube collected. Cell count is performed on tube #3.
Susceptibility testing automatically performed for CSF shunt or lumbar puncture specimens.

Cystic Fibrosis Cultures
Respiratory cultures from CF patients are a specific order. Upon isolation of glucose -non-fermenting
gram-negative rods including P. aeruginosa, susceptibilities by E-test method are performed for
inpatients. Extended incubation times may be required for mucoid and slow growing CF isolates.

HSV Testing
Complete testing for neonatal HSV includes collection of surface swabs (eye, throat, nasal and rectum),
lesion swab (if present), blood, and CSF for HSV PCR. CSF can be tested for HSV by MEP or HSV
PCR. Collect lesion/ulcer specimens using special swabs and viral transport medium obtained from
Microbiology. Unroof lesion if possible and send for HSV PCR. If scab is present, collect whole scab
in transport medium and order HSV PCR. Call Microbiology if antiviral susceptibility testing is
needed.

Tissues and Aspirates
Tissues and aspirates (not swabs) are the preferred diagnostic specimens fo r wound and tissue
infection. The quantity of specimen contained on a swab is usually insufficient for a good culture and
does not permit a Gram stain to be performed. Swabs also retain >70% of the bacteria collected so
cultures are compromised: Get fluid in a syringe if possible. For minute specimen volumes (may not
be visible in the syringe), inoculate a blood culture bottle using the aspiration needle directly, drawing
up liquid from bottle and injecting it back into the bottle to rinse contents of syringe into bottle.

Isolates recovered from swabs and other sources that are potentially contaminated with normal flora are
only tested for susceptibilities when one or two recognized pathogens are recovered. Please see the
Laboratory Test Directory for specific collection instructions for each test and swab type , if swab
cannot be avoided.

                                                      15
Tissues and Aspirates - Anaerobic Cultures
Isolation of anaerobes requires special collection and transport techniques. Please call Micro biology
for appropriate media. Aspirates that are collected from a site that is adjacent to a mucous membrane
are not appropriate for anaerobic culture due to the presence of normal anaerobic flora at these sites.
Susceptibility testing for anaerobes is not available at Children’s Hospital Colorado although most
anaerobes have a predictable susceptibility pattern (see Table 7).

Respiratory Cultures (Tracheal Aspirates)
Susceptibilities are not routinely performed on isolates from tracheal aspirates. Susceptibilities will be
performed on recognized pathogens when a single organism is seen on Gram stain with few or more
polymorphonuclear cells or when a single or predominant organism grows in culture.

TB Sputum and Quantiferon collection
Collect induced sputum or gastric aspirate for TB testing early in the morning for three consecutive
mornings. Blood for Quantiferon testing must be collected following special collection instructions per
laboratory protocol. Specimens that arrive by 6 p.m. will be tested the following Tuesday, Thursday
and Friday.

Urine Cultures
Catheter specimens are preferred. Always exclude the first drops of urine. Avoid “clean catch” or bag
specimens for culture if urinary tract infection (UTI) is likely; especially if antibiotics are to be started.
Please refer to CHCO Clinical Care Guidelines for current recommendations for diagnosis of UTI.
“Clean Catch” or Bag urine cultures are most helpful when they are negative. Be aware that colony
counts may be < 100,000 cfu/mL in any age child with UTI if the specimen is not concentrated, and
that children may have true UTI with multiple organisms. A urine specific gra vity and nitrite test may
help interpret results. For “Catheter”, “Clean Catch” or “Bag” specimens, susceptibilities are
performed automatically on a single isolate with a colony count of 10,000 cfu/mL or greater;
susceptibilities on mixed cultures must be requested. Cotton ball samples are never appropriate for
clinical practice. Please refer to UTI Clinical Care Guideline for additional information.

                                  Antimicrobial Susceptibility Testing

Antimicrobial Susceptibility Testing
Susceptibility testing is performed on significant isolates from the first positive culture from any
source. Additional positive cultures are referred to the first culture on the same or similar source for
three days. Organisms recovered four or more days later will be retested. MRSA, VRE and all
isolates recovered from blood, CSF, brain tissue or aspirate are frozen for future reference. All other
isolates are saved for 7 days before they are discarded.

Susceptibility testing, an important function of the Microbiology Laboratory, is expensive, time
consuming and not required for all isolates. Organisms that have predictable susceptibility patterns do
not require such testing and fastidious isolates may yield results that are difficult to interpret. Multiple
testing methods are utilized because all methods are not suitable for all isolates. The Microbiology
Laboratory has established protocols for testing and reporting of bacterial isolates c ommonly
encountered at CHCO to provide healthcare providers with reliable results. E-test MIC, Microscan
MIC, Sensititre MIC, Kirby Bauer Disk, PBP2A, D-test and Beta-lactamase are all methods utilized to
predict an organism’s antimicrobial susceptibility. CHCO adheres to Clinical and Laboratory
                                                      16
Standards Institute (CLSI) guidelines for susceptibility testing and MICs are interpreted as susceptible,
intermediate and resistant per these guidelines. When choosing a drug for the treatment of an infection,
the site of infection and drug penetration to the site of infection must be considered. Pharmacists or
antimicrobial stewards should be consulted to answer questions re garding pharmacokinetics and
pharmacodynamics of drug-bug interactions.

CRE (Carbapenem Resistant Enterobacteriaceae) Confirmation
CRE are enteric Gram-negative rods that are carbapenem resistant. Different molecular mechanisms
can determine carbapenem resistance including production of a carbapenemase and/or p roduction of an
extended-spectrum Beta-lactamase (ESBL) and/or an AmpC Beta-lactamase in conjunction with
membrane impermeability or active drug efflux.

All enteric Gram-negative rods for which susceptibilities are performed are screened for carbapenem
resistance. Isolates with ertapenem, imipenem, and meropenem MICs in the intermediate or resistant
range are submitted to the CDPHE (Colorado Department of Health and Epidemiology) for screening
and confirmatory testing of carbapenemase production using molecular methods. Consult with
Epidemiology/Infection Control for isolation and Antimicrobial Stewardship and Infectious Disease for
treatment of these patients.

MRSA Confirmation
All S. aureus isolates are tested for vancomycin resistance. Detection of MRSA from a nasal swab
indicates colonization but does not imply systemic colonization. PBP2A Latex Detection, ChromAgar,
Microscan MIC, and cefoxitin screen are methods that the Microbiology Laboratory utilizes for MRSA
confirmation depending on the source.

VRE (Vancomycin Resistant Enterobacteriaceae) Confirmation
Vancomycin resistance in Enterococcus spp. isolates is mediated by van genes that encode enzymes
that modify the vancomycin binding target. Glycopeptide resistance in enterococci may be intrinsic or
acquired. Intrinsic vancomycin resistance is encoded by the vanC gene, which is found chromosomally
in Enterococcus gallinarum and Enterococcus casseliflavus. Intrinsic resistance typically produces
MICs of 2 – 32 mcg/mL for vancomycin, and these organisms are generally susceptible to ampicillin.
Organisms that display this low level intrinsic resistance mechanism are not particularly concerning
from an infection control standpoint and they are not considered to be vancomycin resistant enterococci
(VRE).

Acquired vancomycin resistance is encoded by the vanA and vanB genes and is found in E. faecalis, E.
faecium, and rarely in E. durans. Strains that harbor the vanA gene have high levels of resistance to
vancomycin and teicoplanin, whereas strains that harbor the vanB gene have variable levels of
resistance to vancomycin only. These organisms are true VRE and are an infection control concern
because the genes are transmitted between organisms on plasmids. This type of resistance is associated
with increased morbidity and mortality, particularly in immune-compromised patients.

Enterococcus spp. isolates that test resistant or intermediate to vancomycin by Microscan panel are re -
identified using Maldi-TOF. MICs to vancomycin are confirmed using the E-test method.

                                                   17
Critical and Urgent Value Reporting Policy for Microbiology
Critical Values- The following critical results are phoned directly to the patient’s licensed caregiver
within 30 minutes for inpatients and within 60 minutes for outpatients:
1.    Positive blood culture Gram stain report (first positive)
2.    Positive CSF Gram stain report (first positive)
3.    Positive CSF culture report (first positive)
4.    Positive HSV PCR on CSF, blood or swab specimen from a neonate (first positive)
5.    MEP positive for bacteria, Cryptococcus, HSV or VZV (first positive)
6.    Positive Pneumocystis stain
Urgent Values- The following results are called to the patient’s licensed caregiver or nurse within 8
hours for inpatients or the next business day for outpatients (first positive stain, culture or PCR):
1.     Blood or CSF culture definitive identification of isolate, including results of BCID
2.     Subsequent CSF or Blood culture positives in a series
3.     MEP positive for CMV, HHV6, enterovirus or parechovirus
4.     Single organism isolated from a tissue, aspirate or surgical site or BCID on positive broth
5.     Methicillin Resistant Staphylococcus aureus (MRSA) by culture or PCR (first positive)
6.     Penicillin resistant Streptococcus pneumoniae
7.     Vancomycin resistant Enterococcus faecalis, Enterococcus faecium, Enterococcus durans (VRE)
8.     Drug Resistant Organism
9.     Group A streptococcus throat or rectal (Network of Care and ED obtain reports via Epic In -box)
10.    Group A streptococcus from non-throat or non-rectal sources are called to all sites
11.    Fusobacterium spp. isolated from any site
12.    GIP positive for Salmonella spp or, Shigella spp.in patients less than 6 months of age
13.    GIP positive for E. coli 0157 or positive shiga-toxin
14.    Legionella spp. isolated from any culture
15.    Fungal mold isolates except CF sputa and dermatophytes
16.    Mycobacterium spp.: positive stain for Acid-Fast Bacilli (AFB), Mycobacterium spp., first
       positive culture, Mycobacterium tuberculosis detected/isolated
17.    Positive test for syphilis (first positive)
18.    Positive C. difficile PCR (first positive)
19.    Positive N. gonorrhoeae or Chlamydia trachomatis PCR with confirmation requested or from a
       CHIP patient
20.    Positive B. pertussis or B. parapertussis PCR
21.    Positive Enterovirus PCR
22.    First positive CMV, EBV, Adenovirus, or HHV6 PCR
23.    HSV PCR - non-CSF, Blood and subsequent positives
24.    HSV or CMV detected by any method on any source from neonates
19
MRSA and VRE Rates Non-Surveillance Culture

             Percent of all S. aureus that are identified as MRSA
                                                                    Overall MRSA Rate
                           from Children's Patients
                                                                    ED/NOC MRSA Rate

                                                                    Inpatient MRSA Rate

       60%

       50%

       40%
Rate

       30%

                                                                                          20
       20%

       10%

       0%

                                                    Year
21
Influenza Virus Treatment

The viral neuraminidase inhibitors osteltamivir (Tamiflu®) is an FDA approved antiviral medication
currently available for the treatment or prophylaxis of influenza virus infections of children. Peramivir
(Rapivab ®) is a similar medication licensed only for treatment of patients 18 years old and older. The
neuraminidase inhibitors are active against influenza A and influenza B viruses. In the 2017-18
influenza season, almost all characterized influenza virus isolates were sensitive in vitro to these
medications.

When started within the first two days of onset of influenza illness, oseltamivir can reduce illness
severity and shorten the duration of fever and symptoms of uncomplicated influenza by an average of
1-2 days in healthy outpatients. These medications may also reduce the risk of serious influenza-
related complications (e.g., pneumonia, respiratory failure, exacerbation of chronic diseases and death).
When clinically indicated, oseltamivir should be started as soon as possible after symptom onse t,
ideally within 48 hours of symptom onset. Treatment should not wait for laboratory
confirmation of influenza. Many experts would start antiviral treatment for any child ill enough
to be hospitalized with a clinical diagnosis of influenza. Treatment started 4-5 days after symptom
onset may still be beneficial in preventing influenza-related complications and deaths in patients at
high risk of such complication or with severe or progressive influenza.

                            Duration of Treatment or Chemoprophylaxis
           Treatment                  Recommended duration for antiviral treatment is 5
                                      days.
           Chemoprophylaxis           Recommended duration is 7 days after exposure. For
                                      control of outbreaks in long-term care facilities and
                                      hospitals, CDC recommends antiviral
                                      chemoprophylaxis for a minimum of 2 weeks,
                                      included vaccinated persons, and up to 1 week after
                                      the last known case was identified.

                                                    22
Antiviral Medications Recommended for Treatment and Chemoprophylaxis of Influenza,
                                             2017 – 2018 Influenza Season
                                        FDA         Not
 Antiviral    Activity
                             Use      approved recommended              Children                   Adults          Adverse events
  agent       against
                                         for     for use in
Oseltamivir   Influenza   Treatment   2 weeks               If < 1 yr old, the dose is 3        75 mg          Adverse events:
(Tamiflu®)    A and B                 and older             mg/kg/dose twice daily.             twice daily    nausea, vomiting.
                                                                                                               Transient
                                                                If > 1 yr old and weight 15 kg                 neuropsychiatric events
                                                                or less, the dose is 30 mg twice               (self-injury or delirium)
                                                                a day; weight > 15 to 23 kg, the               mainly reported among
                                                                dose is 45 mg twice a day;                     Japanese adolescents
                                                                weight > 23 to 40 kg, the dose                 and adults.
                                                                is 60 mg twice a day; more than
                                                                40 kg, the dose is 75 mg twice a
                                                                day.
                          Chemo-      1 yr and                  If child is < 3 months old,       75 mg once
                          prophylaxis older                     chemoprophylactic use is not      daily
                                                                recommended unless situation

                                                                                                                                           23
                                                                is judged critical because of
                                                                limited data on use in the age
                                                                group.
                                                                If child is 3 months - 1 year,
                                                                dose is 3 mg/kg once daily.
                                                                Greater than 1 yr:
                                                                weight 15 kg or less, the dose is
                                                                30 mg once daily;
                                                                weight > 15 to 23 kg, the dose
                                                                is 45 mg once daily;
                                                                weight > 23 to 40 kg, the dose
                                                                is 60 mg once daily;
                                                                more than 40 kg, the dose is 75
                                                                mg once daily.
Antiviral Medications Recommended for Treatment and Chemoprophylaxis of Influenza,
                                            2017 – 2018 Influenza Season
                                          FDA         Not
  Antiviral    Activity
                              Use      approved recommended              Children               Adults         Adverse events
   agent       against
                                           for     for use in
Peramivir      Influenza   Treatment   2 years                 Birth – 3 months, 6 – 10       600 mg IV    Diarrhea, vomiting,
(Rapivab®)     A and B                 and older               mg/kg IV once daily; greater   once daily   neutropenia
                                                               than 3 months – 17 years, 10
                                                               mg/kg IV once daily
Zanamivir*     Influenza   Treatment   7 years   People with   10 mg (2 inhalations) twice    10 mg (2     Allergic reactions:
(Relenza®)     A and B                 and older underlying    daily                          inhalations) oropharyngeal or facial
                                                 respiratory                                  twice daily edema.
                                                 disease (e.g. (Not FDA approved for use                   Adverse events:
                                                 asthma,       in children < 7 years old)                  diarrhea, nausea,
                                                 COPD)                                                     sinusitis, nasal signs
                                                                                                           and symptoms,
                                                                                                           bronchitis, cough,
                                                                                                           headache, dizziness,
                                                                                                           and ear, nose and throat

                                                                                                                                      24
                                                                                                           infections.
                           Chemo-      5 years                   10 mg (2 inhalations) once   10 mg (2
                           prophylaxis and older                 daily                        inhalations)
                                                                                              once daily
*Not on CHCO                                                     (Not FDA approved for use
formulary                                                        in children < 5 years old)
Guidelines for Changing from IV to PO Antibiotics in Hospitalized Children
                      Over 2 Months of Age at Children’s Hospital Colorado

CONSIDERATIONS / BASIC PRINCIPLES:
Advantages of an IV to PO conversion are to provide an oral or enteral dosage form with comparable
bioavailability to the intravenous form. This could reduce hospital length of stay and will avoid added
risks associated with continued intravenous therapy. This will lower the overall medication and
associated costs to the patient and the hospital.

PROTOCOL:
1) Antimicrobial Therapy
   a) The following antimicrobials have an oral analogue with greater than or equal to 90%
      bioavailability and may be switched at or after initiation of treatment:
      i) Antimicrobials
         • Rifampin
         • Metronidazole
         • Levofloxacin / ciprofloxacin*
         • Clindamycin
         • Linezolid
         • Fluconazole
         • Bactrim (sulfamethoxazole / trimethoprim) [dose based on trimethoprim]
           * ciprofloxacin is 80% bioavailable

      ii) Recommend changing from IV to PO if:
          1) Clinically stable
          2) Tolerating enteral nutrition by the oral, gastric, or other appropriate enteral tube
          3) Tolerating other medications by the oral route
          4) Medical and social situation will allow patient to comply with oral antibiotic therapy once
             discharged from the hospital

      iii) Consider continuing IV therapy if:
           1) NPO including medications
           2) Unable to tolerate oral formulation
           3) Presence of vomiting or diarrhea in the previous 24 hours, gastrointestinal obstruction,
              malabsorption syndrome, or ileus
           4) Antimicrobial being used for bacteremia/line infection
           5) Conversion to oral dose of clindamycin greater than 1.8 gm/day
           6) Receiving continuous enteral feeds that cannot be interrupted and the antibiotic must be
              given on an empty stomach
           7) Severe Sepsis (with organ dysfunction)
           8) CNS Infection, endovascular infection
           9) Fever and Neutropenia

                                                   25
b) Changing from IV to PO when there is LESS THAN 90% bioavailability. The following
      related antimicrobial alternatives* may be switched after initial intravenous therapy once
      the patient has met the following inclusion criteria and does not meet the following exclusion
      criteria:

       i) Recommend changing from IV to PO if:
           1) Clinically stable
           2) Tolerating enteral nutrition by the oral, gastric, or another appropriate enteral route
           3) Tolerating other medications by the oral route
           4) Signs, symptoms (fever, pain) and indicators of infection (CBC, ESR, CRP) have resolved
              or are improving
           5) Medical and social situation will allow patient to comply with oral antibiotic therapy once
              discharged from the hospital
       ii) Consider continuing IV therapy under the following circumstances:
           1) NPO including medications
           2) Unable to tolerate oral formulation
           3) Presence of vomiting or diarrhea in the previous 24 hours, gastrointestinal obstruction,
              malabsorption syndrome, or ileus
           4) Antimicrobial being used for bacteremia/line infection
           5) Receiving continuous enteral feeds that cannot be interrupted and the antibiotic must be
              given on an empty stomach
           6) Severe Sepsis (with organ dysfunction)
           7) CNS infection or endovascular infection
           8) Fever and Neutropenia

                        Intravenous Antibiotic            Oral Alternative*
                       Cefotaxime, ceftriaxone      **
                       Ampicillin                   Amoxicillin
                       Ampicillin / sulbactam       Amoxicillin / clavulanic acid
                       Cefazolin                    Cephalexin

* Bacterial infections with a known organism and susceptibilities can help guide choosing a well
absorbed unrelated alternative.
** Oral 3 rd gen cephalosporins (i.e. cefdinir) are not well absorbed and do no t provide adequate step-
down therapy. Recommend oral amoxicillin or amoxicillin/clavulanate if sensitive. For PCN allergic,
may use cefuroxime or cefpodoxime; cefdinir has inferior serum levels.

                                                    26
Children’s Hospital Colorado Antimicrobial Formulary
                                                         June 1, 2018
                          IV                     Oral                       Monitor                           DOSE Information
    Antimicrobial
   Formulations at
                                  Oral   Adjust for Bioavailability (Oral
  Children’s Hospital   IV Cost                                                                      IV                             PO
                                  Cost     Food       Alternatives)**
       Colorado

Antivirals
       ACYCLOVIR         $$$       $       w/wo            10-20%             R       HSV encephalitis 3 months or     Suppressive therapy for
                                                                                      less, 20 mg/kg/dose q8h; 4 mos   neonates and recurrent
                                                                                      or greater, 10 mg/kg/dose qh8    herpes 20 mg/kg/dose TID

                                                                                                                       HSV/Varicella treatment: 20
                                                                                                                       mg/kg/dose QID

                                                                                                                       VZV treatment 20 mg/kg/dose
                                                                                                                       5 times daily (max 800
                                                                                                                       mg/dose)

                                                                                                                                                        27
                                                                                                                       Available dosage forms: 200
                                                                                                                       mg caps; 400, 800 mg tabs; 200
                                                                                                                       mg/6 mL susp
      CIDOFOVIR         $$$$$                                                 R       5 mg/kg/dose q1-2 weeks; must
                                                                                      be given with probenecid
     FOSCARNET           $$$$                                                 R       CMV Treatment 60 mg/kg/dose
                                                                                      q8h or 90 mg/kg/dose q12h

                                                                                      Maintenance 90 – 120
                                                                                      mg/kg/dose q24h
    GANICICLOVIR         $$$      $$$        w             6 – 9%           R, CBC    CMV prophylaxis 5 mg/kg/dose
                                                                                      q24h

                                                                                      CMV treatment 5 mg/kg/dose
                                                                                      q12h

                                                                                      Neonatal CMV treatment 6
                                                                                      mg/kg/dose q12h

                                                                                      * refer to specific transplant
                                                                                      protocol for dosing
IV                    Oral                        Monitor        DOSE Information
  Antimicrobial
 Formulations at
                                Oral   Adjust for Bioavailability (Oral
Children’s Hospital   IV Cost                                                       IV                         PO
                                Cost     Food       Alternatives)**
     Colorado

 VALACYCLOVIR                   $$       w/wo           55% once            R                     Treatment of HSV
                                                       converted to                               > 3months: 40-60 mg/kg/day
                                                        acyclovir                                 divided TID (max 2000-3000mg
                                                                                                  daily)
                                                                                                  > 12 yrs: 40-60 mg/kg/day
                                                                                                  divided BID-TID

                                                                                                  Treatment of VZV
                                                                                                  > 3 months: 60 mg/kg/day
                                                                                                  divided TID (max 3000mg daily;
                                                                                                  1000mg per dose)

                                                                                                  Suppression of HSV
                                                                                                  > 3months: 40-60 mg/kg/day
                                                                                                  divided BID (max 1000mg per
                                                                                                  day)

                                                                                                                                   28
                                                                                                  > 12 yrs: 40-60 mg/kg/day
                                                                                                  divided daily or BID (max
                                                                                                  1000mg per day)
VALGANCICLOVIR                  $$       w/wo           60% once          R, CBC                  Treatment of CMV
                                                       converted to                               15-18 mg/kg/dose BID (Max
                                                        ganciclovir                               900 mg/dose)

                                                                                                  Prophylaxis/suppression
                                                                                                  15-18 mg/kg/dose Qday (Max
                                                                                                  900 mg/dose)
IV                        Oral                           Monitor                           DOSE Information
    Antimicrobial
   Formulations at
                                  Oral     Adjust for      Bioavailability (Oral
  Children’s Hospital   IV Cost                                                                              IV                              PO
                                  Cost       Food            Alternatives)**
       Colorado

Antifungals
AMPHOTERICIN B            $$                                     See Azoles         R, L     0.5 – 1 mg/kg/day q24h
DEOXYCHOLATE

AMPHOTERICIN B          $$$$$                                    See Azoles         R, L     3 – 5 mg/kg/day q24h, may use 7.5
LIPOSOME                                                                                     mg/kg/dose for lung infections,
                                                                                             doses as high as 10 mg/kg/dose
                                                                                             q24h have been used for CNS
                                                                                             infections
FLUCONAZOLE               $$      $ – $$     w/wo          90%                      R, L     Prophylaxis/oral thrush/urinary       Prophylaxis/oral
                                                                                             tract 3 mg/kg/day;                    thrush/urinary tract 3
                                                                                                                                   mg/kg/day
                                                                                             Oral candidiasis 3 – 6 mg/kg/day
                                                                                                                                   Oral candidiasis 3 – 6
                                                                                             Candidemia 6 – 12 mg/kg/day           mg/kg/day

                                                                                             Esophageal invasive disease           Candidemia 6 – 12
                                                                                             (endocarditis/CNS/endoph              mg/kg/day
                                                                                             thalmitis, etc) 10 – 12 mg/kg/day

                                                                                                                                                              29
                                                                                             Systemic 6 – 12 mg/kg/day             Esophageal invasive
                                                                                                                                   disease (endocarditis/
                                                                                             ***all q24h dosing***                 CNS/ endophthalmitis,
                                                                                                                                   etc.) 10 – 12 mg/kg/day
                                                                                                                                   Systemic 6 – 12
                                                                                                                                   mg/kg/day

                                                                                                                                   *** all q24h dosing***

                                                                                                                                   Available dosage
                                                                                                                                   forms: 25, 50, 100, 150,
                                                                                                                                   200 mg tabs; 40 mg/mL
                                                                                                                                   susp
ITRACONAZOLE                       $$$     w(caps)                 55%             L, TDM                                          3 – 10 mg/kg/day
                                           wo(soln)
                                                                                                                                   Available dosage
                                                                                                                                   forms: 100 mg caps; 10
                                                                                                                                   mg/mL sol
IV                        Oral                           Monitor                           DOSE Information
    Antimicrobial
   Formulations at
                                  Oral     Adjust for      Bioavailability (Oral
  Children’s Hospital   IV Cost                                                                              IV                                 PO
                                  Cost       Food            Alternatives)**
       Colorado

MICAFUNGIN               $$$$                                  See Azoles           R, L,    Prophylaxis
                                                                                    CBC,     Less than 8 years old: 2mg/kg/day
                                                                                    TDM      q24h (max 50mg/dose)
                                                                                             Greater than 8 years old: 1mg/kg/day
                                                                                             q 24 hours (max 50mg/dose)

                                                                                             Treatment:
                                                                                             less than 6 mos: 8 – 10 mg/kg/day
                                                                                             q24h
                                                                                             6 mos – 8 yrs: 4 mg/kg/day q24h
                                                                                             Greater than 8 yrs: 2-3 mg/kg/day
                                                                                             q24h
VORICONAZOLE            $$$$$     $$$$ –       wo                  96%              R, L,    Adult: 12 mg/kg/day divided q12h x     12 years and older: > 40kg
                                  $$$$$                                             CBC,     2 doses then 8 mg/kg/day divided       200 – 300 mg PO BID
                                                                                    TDM      q12h
                                                                                                                                    Neonate: 12 – 20 mg/kg/day
                                                                                             Neonate: 12 – 20 mg/kg/day divided     divided q12h
                                                                                             q8 – 12h
                                                                                                                                    Greater than 2 years: 18

                                                                                                                                                                 30
                                                                                             Less than 2 yrs: 18 mg/kg/day          mg/kg/day divided q12h
                                                                                             divided q12h
                                                                                                                                    Available dosage forms:
                                                                                             Greater than 2 yrs: 18 mg/kg/day       50, 100, 200 mg tabs; 40
                                                                                             divided q12h                           mg/mL susp

POSACONAZOLE            $$$$$     $$$$ –   Liquid with       Liquid (variable)      R, L,    Adult: 300 mg IV q24h                  100 mg DR tab:
                                  $$$$$       food           Tablet (54-70%)        CBC,                                            Adult 300 mg po daily
                                                                                    TDM      Children: 7 – 10 mg/kg/day has         Children 7-10 mg/kg/day
                                                                                             been used
                                                                                                                                    40 mg/ml Liquid:
                                                                                                                                    Adult 400 mg BID or 200 mg
                                                                                                                                    QID

                                                                                                                                    Children 12 – 20 mg/kg/day
                                                                                                                                    divided QID has been used
IV                      Oral                           Monitor                          DOSE Information
   Antimicrobial
  Formulations at
                                   Oral   Adjust for         Bioavailability
 Children’s Hospital     IV Cost                                                                        IV                              PO
                                   Cost     Food          (Oral Alternatives)**
      Colorado

Antibacterials
AMIKACIN                   $$                          Check Susceptibilities R, TDM        7.5 mg/kg/dose q8h
GENTAMICIN                 $                           Check Susceptibilities R, TDM        Neonates: see formulary;

                                                                                            Children: 2.5 mg/kg/dose
                                                                                            q8h
TOBRAMYCIN                 $$                          Check Susceptibilities R, TDM        2.5 mg/kg/dose q8h
AMOXICILLIN                         $       w/wo              89%                R                                     AOM 90 mg/kg/day divided BID
(preferred regimen for
CAP)                                                                                                                   CAP 90 mg/kg/day divided TID

                                                                                                                       UTI 25-50 mg/kg/day divided TID

                                                                                                                       Strep throat 50 mg/kg/day divided BID
                                                                                                                       or Qday

                                                                                                                       Available dosage forms: 250, 500 mg
                                                                                                                       caps; 250, 400 chewable; 875 mg tab

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AMOXICILLIN-                        $$      w/wo                  89%               R                                  High dose formulation:
CLAVULANATE
                                                                                                                       CAP 90 mg/kg/day divided
                                                                                                                       TID

                                                                                                                       AOM 90 mg/kg/day divided BID

                                                                                                                       Available dosage forms: 600-42.9
                                                                                                                       mg/5 mL susp, 875-125 mg tabs

                                                                                                                       Regular formulation:

                                                                                                                       UTI 25-50 mg/kg/day divided TID

                                                                                                                       Available dosage forms: 200-28.5,
                                                                                                                       250-62.5, 400-57 mL susp; chewable
                                                                                                                       tabs; 250-125, 500-125 tabs
IV                          Oral                           Monitor                             DOSE Information
  Antimicrobial
 Formulations at
                                  Oral       Adjust for    Bioavailability (Oral
Children’s Hospital   IV Cost                                                                                  IV                         PO
                                  Cost         Food          Alternatives)**
     Colorado

Antibacterials
AMPICILLIN-            $$$         See                    Check Susceptibilities     R       UTI 100 – 200 mg/kg/day divided q6h
SULBACTAM                         Amox/
                                   Clav                                                      Bacteremia/CAP/SSTI 200 mg/kg/day
                                                                                             divided q6h

                                                                                             Meningitis 200 – 400 mg/kg/day
                                                                                             divided q4 – 6h (max 2gm/dose)
NAFCILLIN              $$$         See                    Check Susceptibilities R, CBC,     Moderate infection 50 – 100
                                Cephalexin                                         UA        mg/kg/day divided q6h
                                  Diclox
                                                                                             Severe 100 – 200 mg/kg/day divided q4
                                                                                             – 6h (max dose 2 gm/dose)

                                                                                             Can infuse as continuous infusion (200
                                                                                             mg/kg/day max 10gm /day)
PENICILLIN G            $        See Pen                                             R       Mild to moderate infections 100,000
Potassium                           V                                                        to 250,000 units/kg/24 hours in divided
                                                                                             doses every 4 – 6 hours;

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                                                                                             Severe infections Up to 400,000
                                                                                             units/kg/24 hours in divided doses ever
                                                                                             4 – 6 hours (max dose 24 million
                                                                                             units/24 hours)
PENICILLIN G           $$$       See Pen                                             R       (For IM Administration ONLY)
BENZATHINE                          V                                                        Group A streptococcal upper
600000 UNIT/ML                                                                               respiratory infection
IM SUSP (For IM                                                                              25,000 units/kg as a single dose;
Administration                                                                               maximum 1.2 million units;
Only)
                                                                                             Prophylaxis of recurrent rheumatic
                                                                                             fever 25,000 units/kg every 3 – 4
                                                                                             weeks; maximum: 1.2 million units per
                                                                                             dose

                                                                                             Syphilis – please refer to CDC
                                                                                             recommendations for dosing and
                                                                                             duration.
IV                      Oral                      Monitor                             DOSE Information
     Antimicrobial
    Formulations at
                                   Oral      Adjust Bioavailability (Oral
   Children’s Hospital   IV Cost                                                                     IV                                  PO
                                   Cost     for Food  Alternatives)**
        Colorado

PENICILLIN V                         $        wo            25 – 60%           R                                         25 – 50 mg/kg/24 hrs divided every 6
POTASSIUM                                                                                                                – 8 hrs (max 500 mg/dose)

                                                                                                                         Available dosage forms: 125, 250,
                                                                                                                         500 mg tabs; 250 mg/5 mL susp
PIPERACILLIN-            $$$$$                               Check            R, L     Dose based on piperacillin: 240
TAZOBACTAM                                                Susceptibilities             – 400 mg/kg/day (max 4
                                                                                       gm/dose) divided 6-8 hrs
Cephalosporins
First Generation
CEFAZOLIN                  $$       See                      Check             R       50 – 150 mg/kg/day divided q6-
SODIUM                             Ceph-                  Susceptibilities             8h (max 2 gm/dose, 6 gm/day)
                                   alexin
                                   Diclox
CEPHALEXIN                           $       w/wo              90%             R                                         General dosing 50 mg/kg/day
                                                                                                                         divided QID

                                                                                                                         Osteo 100 -150 divided QID (max
                                                                                                                         1gm/dose)

                                                                                                                                                                33
                                                                                                                         Available dosage forms: 250, 500
                                                                                                                         mg caps; 250 mg/5 mL susp
Second Generation
CEFOXITIN                 $$$                                                  R       Neonates: 90 – 100 mg/kg/day
                                                                                       divided q8h

                                                                                       Children: 160 mg/kg/day
                                                                                       divided q4 – 6h (max 2
                                                                                       gm/dose)
CEFUROXIME SODIUM         $$$       $$        w/wo          37 – 52%           R       75 -150 mg/kg/day divided q8h     20 – 30 mg/kg/day divided BID (max
                                             (tabs)                                    (max 2 gm/dose)                   500 mg/dose)
                                            w(susp)
                                                                                                                         Available dosage forms: 62.5, 125,
                                                                                                                         250, 500 mg tab; 125 mg/5 mL susp
IV                      Oral                            Monitor                         DOSE Information
     Antimicrobial
    Formulations at
                                   Oral   Adjust for      Bioavailability (Oral
   Children’s Hospital   IV Cost                                                                             IV                              PO
                                   Cost     Food            Alternatives)**
        Colorado

Third Generation
CEFOTAXIME                $$$                             Check Susceptibilities     R       General dosing 100-200 mg/kg/day
                                                                                             divided q6 – 8h

                                                                                             Meningitis 200 – 300 mg/kg/day
                                                                                             divided q6 (max 2 gm/dose)
CEFTRIAXONE                $$                             Check Susceptibilities             General dosing 50 – 75 mg/kg/day
                                                                                             divided q12 – 24

                                                                                             Meningitis and osteo 100
                                                                                             mg/kg/day divided q12 – 24h (max 2
                                                                                             gm/dose)
CEFIXIME                           $$$      w/wo                40 – 50%             R                                            8 mg/kg/day in 1 – 2
                                                                                                                                  divided doses (max 400
                                                                                                                                  mg/day)

                                                                                                                                  Available dosage forms:
                                                                                                                                  100, 200, 400 mg tabs; 100
                                                                                                                                  mg/5 mL susp

                                                                                                                                                               34
CEFTAZIDIME               $$$                             Check Susceptibilities     R       100 – 150 mg/kg/day divided q8h
                                                                                             (max 2 gm/dose)
CEFTAZIDIME-              $$$                             Check Susceptibilities     R       100-150 mg/kg/day divided q8h (max
AVIBACTAM                                                                                    2 gm/dose)
Fourth Generation
CEFEPIME HCL INJ          $$$                             Check Susceptibilities     R       100 mg/kg/day divided q12h

                                                                                             F&N and serious infections 150
                                                                                             mg/kg/day divided q8h (max 2
                                                                                             gm/dose)
Fifth Generation
CEFTAROLINE               $$$                             Check Susceptibilities     R       Infants 2 months to under 6
                                                                                             months of age: 10 mg/kg/dose
                                                                                             every 8 hours

                                                                                             Infants (6 months of age and
                                                                                             older), Children, Adolescents: 15
                                                                                             mg/kg/dose (max: 600 mg per dose)
                                                                                             every 8 hours
IV                      Oral                            Monitor                         DOSE Information
     Antimicrobial
    Formulations at
                                   Oral   Adjust for      Bioavailability (Oral
   Children’s Hospital   IV Cost                                                                             IV                               PO
                                   Cost     Food            Alternatives)**
        Colorado

CEFTOLOZANE-              $$$                             Check Susceptibilities     R       General Dosing: 20 to 40
TAZOBACTAM                                                                                   mg/kg/dose (based on ceftolozane
                                                                                             component) IV q 8 hours, max dose
                                                                                             of 2000 mg of ceftolozane

                                                                                             Cystic Fibrosis and VAP/HAP:
                                                                                             40 mg/kg/dose (based on ceftolozane
                                                                                             component) IV q 8 hours, max dose
                                                                                             of 2000 mg of ceftolozane

Carbapenems
MEROPENEM                 $$$                                   Check              R, L,     Moderate infection 60 mg/kg/day
                                                             Susceptibilities      CBC       divided q8h (max 1 gm/dose);

                                                                                             Meningitis 120 mg/kg/day divided
                                                                                             q8h (max 2gm/dose)
Macrolide/Azalides

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AZITHROMYCIN                        $       w/wo                  38%                        10 mg/kg/day q24h (max 500 mg)        10 mg/kg/day, day 1 (max
                                                                                                                                   500 mg), then 5 mg/kg/day
                                                                                                                                   (max 250 mg)

                                                                                                                                   Campylobacter and
                                                                                                                                   shigellosis 10 mg/kg/day x
                                                                                                                                   3 days

                                                                                                                                   Salmonella (enteric
                                                                                                                                   fever/typhoid)
                                                                                                                                   10mg/kg/day X 5-7 days

                                                                                                                                   Available dosage forms:
                                                                                                                                   125, 250 mg tabs; 200
                                                                                                                                   mg/5 mL susp
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