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Home , Ampicillin, Aztreonam, Cefazolin, Cefuroxime, Gram stain, Methicillin

TREATMENT GUIDELINE FOR ADULT PATIENTS WITH BLOODSTREAM

Purpose: This guideline is intended to help guide antimicrobial therapy for patients admitted to adult 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.

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: or CNS : 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. ADULT 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 of blood cultures and fluconazole susceptibility

All Candida species: Otherwise: Continue Micafungin Micafungin : Micafungin See Candidemia Guideline. Therapy should not be de- See Candidemia Guideline. Therapy should not be de- escalated until guideline criteria are met. escalated until guideline criteria are met, in conjunction Consult ID with ID consult recommendations ID consult is strongly recommended. If suspicion for Cryptococcus or If concern for urinary, ocular, endocarditis, or CNS Histoplasmosis C. glabrata with fluconazole MIC 8 (SDD): infection, alternative therapy may be needed. Consider de-escalation to Fluconazole for clinically stable (fungemia in setting Consult with ID of or patients with clearance of blood cultures in immunocompromised Otherwise: patient), call Micafungin Infectious Diseases consult service for immediate Cryptococcus spp.: Cryptococcus spp.: recommendations Liposomal (Ambisome ) Fluconazole may be appropriate for step down therapy + Flucytosine when criteria is met in conjunction with ID consult recommendations Consult ID

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

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES

S. aureus and mecA negative: Endocarditis or CNS infection: 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: Oxacillin S. lugdunensis: Life-threatening PCN allergy: Vancomycin Vancomycin S. aureus or S. lugdunensis intermediate or resistant to Consult ID methicillin: Vancomycin Consider discontinuing adjunctive gram-negative therapy between 48-72 hours if cultures are negative for gram- negative pathogens, except for patients with intra- *Gram-positive cocci abdominal infections in clusters: Vancomycin Single positive culture for -negative susceptibilities are only performed when or S. epidermidis in suspected infection of coagulase-negative Staphylococcus or S. epidermidis grow prosthetic material, , or in hemodynamically from 2 or more bottles. unstable patients: If growth from 1 bottle, assess for possible S. epidermidis and mecA negative: source of infection, repeat blood cultures, and hold Cefazolin if clinically stable

S. epidermidis and mecA positive or coagulase negative Coagulase-negative Staphylococcus or S. epidermidis Staphylococcus: sensitive to methicillin: Vancomycin Non-CNS/endocarditis: Cefazolin CNS infection or endocarditis: Oxacillin For patients who do not meet the above criteria, a single Life-threatening PCN allergy: Vancomycin positive culture for coagulase-negative Staphylococcus or S. epidermidis may represent contamination, assess for Coagulase-negative Staphylococcus or S. epidermidis possible source of infection and hold antibiotics if intermediate or resistant to methicillin: clinically stable Vancomycin ADULT 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: or Life-threatening PCN allergy or ampicillin-resistant Gram-positive cocci in for BMT patients with ANC <1,000 Enterococcus: chains or pairs: Vancomycin Vancomycin E. faecium and vanA/vanB negative: Vancomycin Patients with vancomycin allergy or ampicillin and Heme-onc, SICU, solid vancomycin-resistant Enterococcus: organ transplant: E. faecium and vanA/vanB positive: Linezolid or Linezolid Linezolid or Daptomycin for BMT patients with ANC <1,000 Daptomycin for BMT patients with ANC <1,000 BMT with ANC Patients with suspected endocarditis will likely require 1,000: E. casseliflavus, E. gallinarium: combination therapy and ID consult is strongly Linezolid Linezolid or recommended Daptomycin for BMT patients with ANC <1,000 BMT with ANC <1,000: Other Enterococcus species: Daptomycin Vancomycin

S. pneumoniae, S. anginosus or Penicillin-based antibiotics should be first line therapy species: for all Streptococcus species infections, Non-CNS/endocarditis: if sensitive: CNS infection or endocarditis: Ceftriaxone + Vancomycin Penicillin or Ampicillin Febrile neutropenia: Vancomycin + anti-Pseudomonal beta-lactam Mild PCN allergy: Cefazolin (if no CNS infection) Mild PCN allergy CNS infection: Ceftriaxone S. agalactiae or S. pyogenes: Life-threatening PCN allergy: Vancomycin Penicillin or Ampicillin Febrile neutropenic patients should be continued on anti- Mild PCN allergy: Cefazolin (if no CNS infection) Life-threatening PCN allergy: Vancomycin Pseudomonal beta-lactam ADULT 5 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES E. coli, , or : No CTX-M, KPC, IMP, VIM, NDM, OXA detected: or Piperacillin-tazobactam

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

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

*Evaluate if patient , , Morganella, or : Narrow antibiotic selection based on susceptibility results, has history of No CTX-M, KPC, IMP, VIM, NDM, OXA detected: clinical status, concomitant infections: resistance to Cefepime piperacillin-  ID consult is strongly encouraged for patients with tazobactam or CTX-M positive: infections from organisms with KPC, IMP, VIM, NDM, cefepime with prior Meropenem or OXA resistance genes year and modify KPC positive: therapy accordingly  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. ADULT 6 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES

Pseudomonas aeruginosa No CTX-M, KPC, IMP, VIM, NDM, OXA detected: Narrow antibiotic selection based on susceptibility results, Cefepime or Piperacillin-tazobactam. Consider empiric clinical status, concomitant infections. double coverage with tobramycin  If isolate is resistant to cefepime, CTX-M positive: piperacillin-tazobactam, meropenem, , Meropenem + aztreonam, and , request ceftolozane-tazobactam, ceftazidime-avibactam, and KPC positive: meropenem-vaborbactam susceptibilities from *Gram-negative Meropenem-vaborbactam + Polymyxin B microbiology lab (phone number 6-6831) bacilli: Piperacillin- IMP, VIM, or NDM positive:  Double coverage of Pseudomonas is not indicated tazobactam Aztreonam + Polymyxin B after susceptibilities are available, unless isolate is or resistant to all beta-lactam antibiotics, Cefepime OXA positive: patient, or decompensating on susceptible antibiotics (add metronidazole Cefepime + Polymyxin B for intra-abdominal infections) Acinetobacter baumanii No CTX-M, KPC, IMP, VIM, NDM, OXA detected: *Evaluate if patient Meropenem + Polymyxin B has history of resistance to Narrow antibiotic selection based on susceptibility results, CTX-M positive: clinical status, concomitant infections. cefepime with prior Meropenem + Polymyxin B year and modify  There is no evidence double coverage of therapy accordingly 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 ADULT 7 of 7

GRAM STAIN ORGANISM IDENTIFICATION SUSCEPTIBILITIES *Gram-negative bacilli: Piperacillin- Achromobacter: tazobactam Piperacillin-tazobactam Narrow antibiotic selection based on susceptibility results, or Life-threatening PCN allergy: Meropenem clinical status, concomitant infections. Cefepime (add metronidazole (Avoid cefepime unless susceptibility is verified)  Achromobacter is frequently multi-drug resistant, and for intra-abdominal ID consult is encouraged to guide appropriate infections) management of these infections Stenotrophomonas:  Trimethoprim-sulfamethoxazole should be dosed 10 Trimethoprim-sulfamethoxazole mg/kg/day in 2-4 divided doses for patients with good *Evaluate if patient Sulfa-allergy: Levofloxacin + minocycline renal function when treating Stenotrophomonas has history of bacteremia resistance to (Piperacillin-tazobactam and cefepime do not have cefepime with prior activity against Stenotrophomonas) year and modify therapy accordingly

Gram-positive rod: Most likely the result of skin flora , , 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, : 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