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TREATMENT GUIDELINE FOR PEDIATRIC PATIENTS WITH BLOODSTREAM INFECTIONS

Purpose: This guideline is intended to help guide antimicrobial therapy for patients admitted to pediatric service lines following the results of Gram Stain, Organism Identification (with or without Verigene™ molecular resistance results) and Antimicrobial Susceptibilities. Deviation from the recommendations in this guideline may be required for patients with concomitant infections, history of resistant pathogens, or with antimicrobial or intolerance.

The recommendations in this guideline reflect susceptibility patterns found at Michigan Medicine and C. S. Mott Children’s Hospital.

How to use this guideline: For patients with ONLY Gram stain results, refer For patients with organism identification results, refer to the For patients with antimicrobial susceptibility results, refer to to the left column middle column (labeled ORGANISM IDENTIFICATION) for the right column (labeled SUSCEPTIBILITIES) for treatment (labeled GRAM STAIN) treatment recommendations recommendations for treatment recommendations

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES

S. aureus and mecA negative: Endocarditis or CNS infection: S. aureus or S. lugdunensis sensitive to : *Gram‐positive Other infections: Non‐CNS/endocarditis: Cefazolin cocci in clusters: CNS infection or endocarditis: Nafcillin S. aureus and mecA positive or mecA not Life‐threatening PCN : Vancomycin performed: Vancomycin S. aureus or S. lugdunensis intermediate or *Single positive resistant to methicillin: cultures from S. lugdunensis: Vancomycin Vancomycin

Antimicrobial Subcommittee Approval: 12/2018 Originated: 12/2018 P&T Approval: 03/2019 Last Revised: 09/2019 Revision History: The recommendations in this guide are meant ot serve as treatment guidelines for use at Michigan Medicine facilities. If you are an individual experience a medical emergency, call 911 immediately. These guidelines should not replace a provider’s profession medical advice based on clinical judgment, or be used in lieu of an Infectious Diseases consultation when necessary. As a result of ongoing research, practice guidelines may from time to time change. The authors of these guidelines have made all attempts to ensure the accuracy based on current information, however, due to ongoing research, users of these guidelines are strongly encouraged to confirm the information contained within them through and independent source.

If obtained from a source other than med.umich.edu/asp, please visit the webpage for the most up‐to‐date document. PEDIATRIC 2 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES

C. albicans, C. parapsilosis, C. tropicalis, C. dublinensis, and C. lusitaniae: Consider de‐escalation to Fluconazole for clinically stable patients with clearance of blood cultures and fluconazole susceptibility All Candida species: Yeast: Otherwise: Neonatal: Consult ID Micafungin Neonatal (<44 weeks Infant – Adult: Micafungin PMA): Consult ID See Candidemia Guideline. Therapy should not be de‐ See Candidemia Guideline. Therapy should not be de‐ escalated until guideline criteria are met, in conjunction Infant (>44 weeks escalated until guideline criteria are met. PMA) – Adult: with ID consult recommendations Micafungin ID consult is strongly recommended.

Consult ID If concern for urinary, ocular, endocarditis, or CNS C. glabrata with fluconazole MIC ≤8 (SDD): infection, alternative therapy may be needed. Consider de‐escalation to Fluconazole for clinically stable If suspicion for Consult with ID patients with clearance of blood cultures Cryptococcus or Histoplasmosis Otherwise: (fungemia in setting Micafungin of or in immunocompromised Cryptococcus spp.: Cryptococcus spp.: patient), call Liposomal amphotericin B (Ambisome™) Fluconazole may be appropriate for step down therapy Infectious Diseases + Flucytosine consult service for when criteria is met in conjunction with ID consult recommendations immediate antifungal Consult ID recommendations

Histoplasma: Histoplasma: Liposomal amphotericin B (Ambisome™) Step down therapy may be appropriate when clinically stable in conjunction with ID consult recommendations Consult ID PEDIATRIC 3 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES

S. aureus and mecA negative: Endocarditis or CNS infection: Nafcillin Other infections: Cefazolin

S. aureus and mecA positive or mecA not performed: S. aureus or S. lugdunensis sensitive to methicillin: Vancomycin Non‐CNS/endocarditis: Cefazolin CNS infection or endocarditis: Nafcillin *Gram‐positive cocci S. lugdunensis: Life‐threatening PCN allergy: Vancomycin in clusters: Vancomycin Vancomycin S. aureus or S. lugdunensis intermediate or resistant to Consult ID methicillin: Vancomycin Consider discontinuing adjunctive gram‐negative therapy *Single positive between 48‐72 hours if cultures are negative for gram‐ cultures from negative pathogens, except for patients with intra‐ peripheral sources in abdominal infections patients without:  Neutropenia  Prosthetic Single positive culture for Coagulase‐negative material Staphylococcus or S. epidermidis in suspected infection of infection prosthetic material, neutropenia, premature neonates, or  Premature in hemodynamically unstable patients: neonates Coagulase‐negative Staphylococcus or S. epidermidis May represent S. epidermidis and mecA negative: sensitive to methicillin: contamination; assess Cefazolin Non‐CNS/endocarditis: Cefazolin for possible source of CNS infection or endocarditis: Nafcillin infection and hold S. epidermidis and mecA positive or coagulase negative Life‐threatening PCN allergy: Vancomycin if clinically Staphylococcus: stable Vancomycin Coagulase‐negative Staphylococcus or S. epidermidis intermediate or resistant to methicillin: For patients who do not meet the above criteria, a single Vancomycin positive culture for coagulase‐negative Staphylococcus or S. epidermidis may represent contamination, assess for possible source of infection and hold antibiotics if clinically stable PEDIATRIC 4 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES E. faecalis and vanA/vanB Negative: (consider as alternative for intra‐ abdominal infections) Life‐threatening PCN allergy: Vancomycin ‐based antibiotics should be first line therapy for all species if sensitive: E. faecalis and vanA/vanB positive: Ampicillin Ampicillin (consider ampicillin‐ or piperacillin‐tazobactam (consider piperacillin‐tazobactam as alternative for intra‐ for intra‐abdominal infections) abdominal infections) Life‐threatening PCN allergy: Linezolid or Life‐threatening PCN allergy or ampicillin‐resistant for BMT patients with ANC <1,000 Enterococcus: Vancomycin E. faecium and vanA/vanB negative: Vancomycin Patients with vancomycin allergy or ampicillin and vancomycin‐resistant Enterococcus: E. faecium and vanA/vanB positive: Linezolid or Linezolid or Daptomycin for BMT patients with ANC <1,000 Gram‐positive cocci in Daptomycin for BMT patients with ANC <1,000 chains or pairs: Patients with suspected endocarditis will likely require Vancomycin E. casseliflavus, E. gallinarium: combination therapy and ID consult is strongly Linezolid or recommended Daptomycin for BMT patients with ANC <1,000

Other Enterococcus species: Penicillin‐based antibiotics should be first line therapy Vancomycin for all Streptococcus species infections, if sensitive: S. pneumoniae, S. anginosus or Penicillin or Ampicillin Streptococcus species: Mild PCN allergy: Cefazolin (if no CNS infection) Non‐CNS/endocarditis: * Mild PCN allergy CNS infection: Ceftriaxone* CNS infection or endocarditis: Ceftriaxone* + Vancomycin Life‐threatening PCN allergy: Vancomycin Febrile neutropenia: Vancomycin + anti‐Pseudomonal beta‐lactam Febrile neutropenic patients should be continued on anti‐ Pseudomonal beta‐lactam S. agalactiae or S. pyogenes: Penicillin or Ampicillin *neonates should receive cefotaxime in the place of Mild PCN allergy: Cefazolin (if no CNS infection) ceftriaxone Life‐threatening PCN allergy: Vancomycin PEDIATRIC 5 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES E. coli, Klebsiella, or Proteus: No CTX‐M, KPC, IMP, VIM, NDM, OXA detected: Ceftriaxone (cefotaxime for neonates)

CTX‐M positive: Narrow selection based on susceptibility results, clinical status, concomitant infections:

KPC positive:  Narrow‐spectrum antibiotics are preferred if no Meropenem‐ resistance or allergies. These include ampicillin, penicillin, ampicillin‐sulbactam, cefazolin, and IMP, VIM, or NDM positive: . + + B*  ID consult is strongly encouraged for patients with *Gram‐negative infections from organisms with CTX‐M, KPC, IMP, VIM, OXA positive: bacilli: NDM, or OXA resistance genes Ceftazidime‐avibactam (add metronidazole *substitute Tobramycin for when treating for intra‐abdominal Proteus infections)

Enterobacter, Serratia, Morganella, or Citrobacter: Narrow antibiotic selection based on susceptibility results, *Evaluate if patient No CTX‐M, KPC, IMP, VIM, NDM, OXA detected: clinical status, concomitant infections: has history of Cefepime resistance to  ID consult is strongly encouraged for patients with cefepime with prior CTX‐M positive: infections from organisms with CTX‐M, KPC, IMP, VIM, year and modify Meropenem NDM, or OXA resistance genes therapy accordingly KPC positive:  Enterobacter, Serratia and Citrobacter freundii Meropenem‐vaborbactam + Polymyxin B* frequently have an inducible beta‐lactamase IMP, VIM, or NDM positive: resistance gene (AmpC), which can confer resistance Ceftazidime‐avibactam + Aztreonam + Polymyxin B* to penicillin, ampicillin, ampicillin/sulbactam, and 1st‐ 3rd generation . Cefepime should be OXA positive: first‐line therapy if susceptible. Ceftazidime‐avibactam  Citrobacter koseri is not associated with having AmpC *substitute Tobramycin for Polymyxin B when treating gene, and narrow spectrum antibiotics should be Morganella or Serratia prescribed if susceptible. PEDIATRIC 6 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES

Narrow antibiotic selection based on susceptibility results, clinical status, concomitant infections. aeruginosa No CTX‐M, KPC, IMP, VIM, NDM, OXA detected: Cefepime  If Pseudomonas isolate is resistant to cefepime, piperacillin‐tazobactam, meropenem, , CTX‐M positive: aztreonam, levofloxacin and ciprofloxacin, request Meropenem ceftolozane‐tazobactam, ceftazidime‐avibactam, and meropenem‐vaborbactam susceptibilities from KPC positive: microbiology lab (phone number 6‐6831) Meropenem‐vaborbactam + Polymyxin B  Double coverage of Pseudomonas is not indicated *Gram‐negative IMP, VIM, or NDM positive: after susceptibilities are available, unless isolate is bacilli: Aztreonam + Polymyxin B resistant to all beta‐lactam antibiotics, cystic fibrosis Cefepime patient, or decompensating on susceptible antibiotics (add metronidazole OXA positive: for intra‐abdominal Cefepime + Polymyxin B  ID consult is encouraged for patients with infections) Pseudomonas bacteremia

*Evaluate if patient Acinetobacter baumanii has history of No CTX‐M, KPC, IMP, VIM, NDM, OXA detected: resistance to Cefepime cefepime with prior Narrow antibiotic selection based on susceptibility results, year and modify CTX‐M positive: clinical status, concomitant infections. therapy accordingly Meropenem  There is no evidence double coverage of KPC positive: Meropenem‐vaborbactam + Polymyxin B Acinetobacter improves outcomes. The decision to double cover should be made based on source of IMP, VIM, or NDM positive: bacteremia, severity of infection, and patient’s Minocycline + Polymyxin B medical history.

OXA positive: Meropenem + Polymyxin B PEDIATRIC 7 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES

*Gram‐negative bacilli: Achromobacter: Cefepime Piperacillin‐tazobactam (add metronidazole Life‐threatening PCN allergy: Meropenem for intra‐abdominal Narrow antibiotic selection based on susceptibility results, infections) (Avoid cefepime unless susceptibility is verified) clinical status, concomitant infections.

 Achromobacter is frequently multi‐drug resistant, and *Evaluate if patient Stenotrophomonas: ID consult is encouraged to guide appropriate has history of Trimethoprim‐sulfamethoxazole management of these infections resistance to Sulfa‐allergy: Levofloxacin + minocycline cefepime with prior year and modify (Piperacillin‐tazobactam and cefepime do not have therapy accordingly activity against Stenotrophomonas)

Gram‐positive rod: Most likely the result of skin flora Bacillus, Lactobacillus, and Corynebacterium spp. are contamination of possible contaminants, consider treatment in HD blood culture unstable, prosthetic material with suspected infection, BMT, solid organ transplant, neutropenia Narrow antibiotic selection based on susceptibility results, Consider treatment in clinical status, concomitant infections. Bacillus or Corynebacterium spp.: Vancomycin HD unstable, prosthetic material  Susceptibilities will not be routinely performed by the Lactobacillus: Piperacillin‐tazobactam with suspected microbiology lab. Please call to request susceptibilities infection, BMT, SOT, Listeria: Ampicillin if strong suspicion for infection Neutropenia: Vancomycin Patients with multiple positive sets of blood cultures are more likely true infection. Consider ID consult. If concern for Listeria: Ampicillin