Bugs and Drugs Handbook 2020 - Children's Hospital Colorado
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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
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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
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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 $$ Check Susceptibilities R, TDM 2.5 mg/kg/dose q8h AMOXICILLIN $ w/wo 89% R AOM 90 mg/kg/day divided BID (preferred regimen for CAP) CAP 90 mg/kg/day divided TID UTI 25-50 mg/kg/day divided TID Strep throat 50 mg/kg/day divided BID or Qday Available dosage forms: 250, 500 mg caps; 250, 400 chewable; 875 mg tab 31 AMOXICILLIN- $$ 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; 32 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 35 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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