Febrile #76 – Pièce de (Gram-negative) Resistance, Part 1: AmpC, ESBL

June 26, 2023

Summary

Welcome to Part 1 of this pair of episodes on management of antimicrobial resistant Gram-negative infections!! Drs. Hawra Al-Lawati and Pranita Tamma walk through the alphabet soup of AmpC and ESBL with 3 mini-cases

Credits

Host(s): Hawra Al-Lawati, Sara Dong

Guest: Pranita Tamma

Writing: Hawra Al-Lawati, Sara Dong

Producing/Editing/Cover Art: Sara Dong

Infographics: Hawra Al-Lawati

Our Guests

Guest Co-Host

Hawra Al-Lawati, MD

Hawra Al-Lawati is a recently graduated adult ID fellow from Beth Israel Deaconess Medical Center in Boston, MA. She is interested in medical education and antimicrobial stewardship. You can find some of her infographic work with prior Febrile episodes #3 (A Transplant Tale) and #6 (The Fever & The Worm).

Guest Discussant

Pranita Tamma, MD, MPH

Pranita Tamma is an Associate Professor of Pediatrics in the Division of Infectious Diseases and Director of the Pediatric Antimicrobial Stewardship Program at Johns Hopkins University. She received her MD from SUNY Downstate Medical Center and then completed pediatric residency and pediatric infectious diseases fellowship training at Johns Hopkins.

Culture

Hawra loved seeing Taylor Swift in concert with friends

Pranita shared her special skill of being able to pick locks

Consult Notes

Key Points

The newest update of the IDSA Guidance on the Treatment of Antimicrobial Resistant (AMR) Gram-negative Infections was released the same month of this episode release!

https://www.idsociety.org/practice-guideline/amr-guidance/

Our guest, Pranita, is the corresponding author on this document, and shared a few notes:

All of the prior documents are now consolidated (AmpC, ESBL, CRE, Pseudomonas, CRAB, Acinetobacter, Stenotrophomonas)
The goal is to update the formal guidance once a year, but there is an online version that does get updated in real time
Table 2 is a new addition which includes the Clinical and Laboratory Standards Institute (CLSI) susceptibility criteria
A supplemental section was also included which provides a little more guidance on where the dosing suggestions came from

This episode focused on AmpC and extended spectrum β-lactamase. You can check out a summary of the cases below

Case 1 (ESBL pyelonephritis)

A 65 year-old woman presents to the ED with flank pain and rigors.

About 1 week ago she called her PCP with complaints of dysuria and suprapubic pain which is typical of prior UTI episodes. She was prescribed trimethoprim-sulfamethoxazole but did not improve after 5 days of taking it and started developing low-grade fevers and mild flank pain.
Her PCP then ordered UA, urine cultures and blood cultures and recommended she switch to levofloxacin pending culture results. However in the next 12-24 hours she developed nausea and vomiting and wasn’t able to take levofloxacin.

- She arrives at the ED and IV ceftriaxone was started.
- PMH/PSH:
  - DM A1c of 9% (on metformin and insulin)
  - Works in this hospital as an oncology floor nurse.
  - No known allergies

ED intern pages ID consult team once culture results from PCP office were obtained: blood cultures were without growth but urine cultures grew ceftriaxone-resistant E. coli.

*Escherichia coli* (urine cultures)
Amox-clav	Resistant
Ceftriaxone	Resistant
Cefepime	Susceptible (MIC <1)
Piperacillin-tazobactam	Susceptible
Meropenem	Susceptible
Levofloxacin	Susceptible
Gentamicin	Susceptible
Nitrofurantoin	Resistant
Trim-sulfa	Resistant

Case 2 (High risk AmpC BSI: K. aerogenes)

45 year old woman presents with perforated diverticulitis and underwent ex-lap with sigmoidectomy. Intra-operative cultures grew Klebsiella aerogenes and ampicillin-susceptible E. faecalis . Blood cultures grew the same Klebsiella aerogenes. The patient received piperacillin-tazobactam peri-op. The surgery resident calls you for guidance on antibiotic since “AmpC” flag came up on the microbiology report for K. aerogenes and she asked if she needs to switch to change antibiotics.

Blood: Klebsiella aerogenes
Amox-clav	Resistant
Ceftriaxone	Susceptible
Cefepime	Susceptible (MIC <1)
Piperacillin-tazobactam	Susceptible
Meropenem	Susceptible
Levofloxacin	Susceptible
Gentamicin	Susceptible

Case 3 (Morganella pyelonephritis + BSI)

77 year old man with history of urinary stones is admitted to the floor with fevers, leukocytosis with CT abdomen showing an obstructing urinary stone in the left kidney and perinephric stranding. He is hemodynamically stable, well appearing and pending urology procedure. Both urine and blood cultures later grew Morganella morganii. One of the residents remembered that this was one of the “SPICE” organisms and asks for help in choosing a regimen.

Amox-clav	Resistant
Ceftriaxone	Susceptible
Cefepime	Susceptible (MIC <1)
Pip-tazo	Susceptible
Meropenem	Susceptible
Levofloxacin	Resistant
Gentamicin	Susceptible

AmpC β-lactamase-producing Enterobacterales

AmpC Basics

AmpC β-lactamases = β-lactamase enzymes produced at basal levels by some Enterobacterales and glucose non-fermenting Gram negative organisms
- - Their primary function is to assist with cell wall recycling
These AmpC β-lactamases can hydrolyze a number of β-lactam agents → sometimes in the setting of basal AmpC production and other times in setting of increased AmpC production
Increased AmpC production by Enterobacterales generally occurs via one of these mechanisms:
- - Inducible chromosomal gene expression
  - Stable chromosomal gene de-repression
  - Constitutively expressed ampC genes (frequently carried on plasmids)
Increased AmpC enzyme production from inducible ampC expression can occur in presence of specific antibiotics and results in enough enough in the periplasmic space to increase the MIC to certain antibiotics
- - Most notably: ceftriaxone, cefotaxime, ceftazidime
  - So in this scenario, an isolate that initially tests susceptible to ceftriaxone may exhibit non-suspectibility to this agent after treatment with ceftriaxone is started
  - In the other two mechanisms, AmpC production is always increased and expected that isolates will test non-susceptible
Several β-lactam antibiotics are at relatively high risk of inducing ampC genes → both the inability to induce ampC genes and the inability to withstand AmpC hydrolysis should inform antibiotic decision making
- - Aminopenicillins (ie amoxicillin, ampicillin), narrow spectrum (1st generation) cephalosporins, and cephamycins are potent ampC inducers
    - - However organisms at mod-high risk for clinically significant ampC induction hydrolyze these antibiotics even at basal ampC expression levels → therefore the isolates with generally test non-susceptible → making treatment decisions easier
  - Imipenem is a potent ampC inducer but generally remains stable to AmpC hydrolysis
  - Piperacillin-tazobactam, ceftriaxone, ceftazidime, aztreonam are relatively weak ampC inducers
    - - Despite their ability to induce ampC, the suscetpibility of these agents to hydrolysis makes them unlikely to be effective for the treatment of infections by organism at mod-high risk for AmpC production
  - Cefepime is both a weak inducer of ampC and can withstand hydrolysis by AmpC β-lactamases → so remains an effective agent
  - TMP-SMX, fluoroquinolones, aminoglycosides, tetracyclines, and other non-beta-lactam drugs do not induce ampC and are not substrates for AmpC hydrolysis

Which Enterobacterales should be considered at moderate to high risk for clinically significant AmpC production due to an inducible ampC gene? What about those acronyms?

Enterobacter cloacae complex

Klebsiella aerogenes

Citrobacter freundii

There are not studies that quantify the exact likelihood of ampC induction across bacteria after beta-lactam exposure, but it is best described for these 3 spp
- - Clinical reports suggest that the emergence of resistance after exposure to an agent like ceftriaxone may occur in ~20% of infections caused by these organisms
  - For these organisms, the IDSA panel recommends avoiding treatment with ceftriaxone or ceftazidime, even if the isolate initially tests susceptible to these agents

As Pranita discussed, commonly used acronyms to denote organisms at risk for AmpC production can obscure the range of ampC induction potential among Gram-negative organisms → it may both under or overcall the likelihood of clinically significant AmpC production among individual bacterial spp. The bottom line is that these acronyms are likely not as accurate as we need them to be
- - These acronyms have included: SPACE, SPICE, ESCPM, HECK-YES
  - Some examples of limitations with the acronyms:
    - - C.freundii harbors a chromosomal ampC whereas C.koseri does not
      - “Indole positive Proteus spp” are often included in existing acronyms, which refers to P.vulgaris and P.penneri, which generally do not contain chromosomal ampC genes. The term used to include Proteus rettgeri and Proteus morganii, which have since been renamed Providencia rettgeri and Morganella morganii, making that inclusion in the mnemonic no longer accurate
  - Some of the organisms historically presumed to be at risk for significant ampC expression, such as Serratia marcescens, Morganella morganii, and Providencia, spp – were found to be unlikely to overexpress ampC based on in vitro and clinical reports → likely occurs in less than 5% of these organisms
  - Additionally some less commonly encountered pathogens (Hafnia alvei, Citrobacter youngae, Yersinia enterocolitica) – there is just limited investigation and not really enough data to tell us whether this is an issue. The IDSA panel recommended using AST results to guide treatment decision in these cases as well
  - All of that said, if a patient has a high bacterial burden; limited source control; inadequate clinical response, it is reasonable to consider cefepime instead of ceftriaxone if you are concerned about possibility of emergence of resistance to the initial agent
Some references:

Cefepime is the recommended treatment for infections caused by organisms at mod-high risk of significant AmpC production (E.cloacae, K.aerogenes, C.freundii)

There were some prior case reports of therapeutic failure of cefepime against AmpC infections which led to prior hesitancy to use this agent → but these had limitations such as the dosing of cefepime used, lack of investigation of concurrent ESBL enzymes
There are not clinical trials comparing clinical outcomes of patients with AmpC infections treated with cefepime vs carbapenem therapy – but there are some observational studies suggesting cefepime would lead to similar outcomes of carbapenem therapy
- - Tamma PD, Girdwood SC, Gopaul R, et al. The use of cefepime for treating AmpC beta-lactamase-producing Enterobacteriaceae. Clin Infect Dis 2013; 57(6): 781-8.
  - Siedner MJ, Galar A, Guzman-Suarez BB, et al. Cefepime vs other antibacterial agents for the treatment of Enterobacter species bacteremia. Clin Infect Dis 2014; 58(11): 1554-63.
  - Tan SH, Ng TM, Chew KL, et al. Outcomes of treating AmpC-producing Enterobacterales bacteraemia with carbapenems vs. non-carbapenems. Int J Antimicrob Agents 2020; 55(2): 105860.
  - Harris PN, Wei JY, Shen AW, et al. Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis. J Antimicrob Chemother 2016; 71(2): 296-306.
    - meta-analysis including seven studies compared clinical outcomes of patients receiving cefepime vs carbapenems for Enterobacter, Citrobacter, Serratia BSI, which didn’t find differences in clinical outcomes between the regimens, although there was a lot of heterogeneity
Pranita discussed how given no clear clinical failure signals, cefepime is preferred agent. That said, the panel does recommend caution for cefepime for infections caused by these 3 organisms with cefepime MICs of 4-8

The role of piperacillin-tazobactam for treatment of infections caused by organisms at mod-high risk of clinically significant inducible AmpC production is uncertain, but the IDSA guidance does not suggest pip-tazo for serious infections.

Tazobactam is less effective at protecting beta-lactams from AmpC hydrolysis than newer beta-lactamase inhibitors like avibactam
A meta-analysis from 2019 summarized 8 observational studies and didn’t identify a difference in mortality in patients treated with pip-tazo vs carbapenems for bacteremia by Enterobacter, Citrobacter, Serratia
- - There was heterogeneity though
  - Cheng MP, Lee RS, Cheng AP, et al. Beta-Lactam/Beta-Lactamase Inhibitor Therapy for Potential AmpC-Producing Organisms: A Systematic Review and Meta-Analysis. Open Forum Infect Dis 2019; 6(7): ofz248.
In two observational studies included in the meta-analysis, 30-day mortality among those treated with pip-tazo was higher than those treated with carbapenems
- - Cheng L, Nelson BC, Mehta M, et al. Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC beta-Lactamase-Producing Enterobacteriaceae. Antimicrob Agents Chemother 2017; 61(6): e00276-17
  - Chaubey VP, Pitout JD, Dalton B, Gregson DB, Ross T, Laupland KB. Clinical and microbiological characteristics of bloodstream infections due to AmpC beta-lactamase producing Enterobacteriaceae: an active surveillance cohort in a large centralized Canadian region. BMC Infect Dis 2014; 14: 647.
There was also an observational study later published that showed pip-tazo monotherapy was associated with over twice the odds of death within 30 days compared to other agents
- - da Cunha Ferreira T, Martins IS. Risk Factors of Death in Bloodstream Infections Caused by AmpC beta-Lactamase-Producing Enterobacterales in Patients with Neoplasia. Infect Drug Resist 2021; 14: 3083-97.
There was also an unblinded clinical trial comparing outcomes between piperacillin-tazobactam or meropenem for bloodstream infections caused by Enterobacter, K.aerogenes, C.freundii, M.morganii, Providenia spp, S.marcescens → there was no different in composite outcome (30-day mortality, clinical failure, microbiological failure, or microbiological relapse) but there were some conflicting findings within the study arms for individual components of the composite outcome – making this challenging to interpret
- - Mortality 0% vs 6%, p=0.13
  - Clinical failure 21% vs 12%, p=0.29
  - Microbiological failure 13% vs 0%, p=0.03
  - Microbiological relapse 0% vs 9%, p=0.06
  - Stewart AG, Paterson DL, Young B, et al. Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC β-Lactamase-Producing Enterobacter spp, Citrobacter freundii, Morganella morganii, Providencia spp, or Serratia marcescens: A Pilot Multicenter Randomized Controlled Trial (MERINO-2). Open Forum Infect Dis 2021; 8(8): ofab387.

As Pranita discussed, the panel suggests caution for pip-tazo for serious infections – although it might be a reasonable option for mild infections such as uncomplicated cystitis

Extended-spectrum β-lactamase-producing Enterobacterales

ESBL Basics

ESBLs are enzymes that inactivate most penicillins, cephalosporins, and aztreonam
ESBLs generally remain susceptible to carbapenems and ESBL does not inactivate non-beta-lactam agents (however may organisms that carry ESBL genes will harbor other additional genes or mutations that mediate resistance to a broad range of antibiotics)
Any Gram negative organisms can harbor ESBL genes → but the most common are E.coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis
CTX-M enzymes are the most common ESBLs in the US
- - Castanheira M, Kimbrough JH, DeVries S, Mendes RE, Sader HS. Trends of β-Lactamase Occurrence Among Escherichia coli and Klebsiella pneumoniae in United States Hospitals During a 5-Year Period and Activity of Antimicrobial Agents Against Isolates Stratified by β-Lactamase Type. Open Forum Infect Dis. 2023;10(2):ofad038. Published 2023 Jan 27. doi:10.1093/ofid/ofad038
  - Tamma PD, Smith TT, Adebayo A, et al. Prevalence of blaCTX-M Genes in Gram-Negative Bloodstream Isolates across 66 Hospitals in the United States. J Clin Microbiol. 2021;59(6):e00127-21. Published 2021 May 19. doi:10.1128/JCM.00127-21
As Pranita discussed, non-susceptibility to ceftriaxone (ceftriaxone MIC ≥2 µg/mL) is often used as a proxy for ESBL production, particularly if seen with the organisms noted above

Preferred antibiotics for treatment of complicated UTI / pyelonephritis caused by ESBL-E:

TMP-SMX, ciprofloxacin, levofloxacin preferred
Carbapenems are preferred (ertapenem, meropenem, imipenem) when resistance or toxicities preclude use to TMP-SMX or FQs
Aminoglycosides for full treatment course are an alternative if the potential for nephrotoxicity is acceptable (just a reminder that the single dose aminoglycosides and oral fosfomycin are alternative treatments for uncomplicated ESBL cystitis but not cUTI/pyelonephritis)

Preferred antibiotics for treatment of non-urinary tract ESBL-E infections:

Meropenem*
Imipenem-cilastatin*
Ertapenem

*Meropenem or imipenem are preferred for critically ill patients or those experiencing hypoalbunemia. Ertapenem is highly protein bound leading to prolonged serum half-life. In those with critical illness, the free fraction of ertapenem increases, leading to significant decrease in serum half-life

A must-know ID clinical trial: The MERINO study established carbapenem therapy as treatment of choice for ESBL bloodstream infections

Harris PNA, Tambyah PA, Lye DC, et al. Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial [published correction appears in JAMA. 2019 Jun 18;321(23):2370]. JAMA. 2018;320(10):984-994. doi:10.1001/jama.2018.12163

Randomized 391 patients with ceftriaxone non-susceptible E.coli or K.pneumoniae (87% later confirmed to have ESBL genes) to receive pip-tazo 4.5g IV Q6h or meropenem 1g IV Q8h, both as standard infusion
Primary outcome of 30-day mortality occurred in 12% and 4% of patients receiving pip-tazo and meropenem, respectively

Henderson A, Paterson DL, Chatfield MD, et al. Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study. Clin Infect Dis. 2021;73(11):e3842-e3850. doi:10.1093/cid/ciaa1479

Trial data was reanalyzed only including patients with clinical isolates against which pip-tazo MICs were ≤16 µg/mL by broth microdilution (reference standard)
- There were a portion of isolates that appeared S to pip-tazo initially but were not in re-analysis
320 patients
30-day mortality was observed in 11% vs 4% of those in pip-tazo and meropenem arms, respectively
Although the absolute risk difference was no longer significant in reanalysis (95% CI ranged =1% to 10%), the IDSA panel favored carbapenem due to the notable direction of risk difference
There are not other clinical trial data for ESBL infections at other body sites, so this has been extrapolated to other common sites of infection

What about piperacillin-tazobactam for treatment of ESBL infections?

The IDSA panel recommends against pip-tazo for serious or bloodstream infections, but…
If pip-tazo is started as empiric therapy for uncomplicated cystitis caused by an organism later identified as ESBL and clinical improvement occurs, no change or extension in antibiotic therapy is necessary

There are concerns regarding tazobactam as an effective beta-lactamase inhibitor because:
- - Pip-tazo MIC testing may be inaccurate and/or poorly reproducible when ESBL enzymes are present or in the presence of other beta-lactamase enzymes – making it unclear if an isolate that tests susceptible is actually susceptible
  - In vitro data suggest pip-tazo may not be effective with increased bacterial inoculum
  - Tazobactam effectiveness may be diminished by organisms with increased expression or ESBL enzymes or by presence of multiple beta-lactamases
  - There are some ESBL enzymes that are not inhibited by beta-lactamase inhibitors
There are some observational studies comparing pip-tazo and carbapenems for treatment of ESBL pyelonephritis and complicated UTI
- - Sharara SL, Amoah J, Pana ZD, Simner PJ, Cosgrove SE, Tamma PD. Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum β-Lactamase-Producing Organisms?. Clin Infect Dis. 2020;71(8):e331-e337. doi:10.1093/cid/ciz1205
    - - This is most robust
      - Included 186 hospitalized patients from 5 hospitals with pyelonephritis or cUTI caused by E.coli, K.pneumo, K.oxytoca, or P.mirabilis (with confirmed ESBL)
      - No difference in resolution of clinical symptoms or 30-day mortality between groups
  - Dizbay M, Özger HS, Karaşahin Ö, Karaşahin EF. Treatment efficacy and superinfection rates in complicated urinarytract infections treated with ertapenem or piperacillin tazobactam. Turk J Med Sci. 2016;46(6):1760-1764. Published 2016 Dec 20. doi:10.3906/sag-1506-157
  - Yoon YK, Kim JH, Sohn JW, Yang KS, Kim MJ. Role of piperacillin/tazobactam as a carbapenem-sparing antibiotic for treatment of acute pyelonephritis due to extended-spectrum β-lactamase-producing Escherichia coli. Int J Antimicrob Agents. 2017;49(4):410-415. doi:10.1016/j.ijantimicag.2016.12.017
  - In the MERINO trial, there was higher mortality in pip-tazo group even though it wasn’t statistically significant
Overall there has been conflicting results on effectiveness of pip-tazo for ESBL

What about cefepime for treatment of ESBL infections?

The IDSA panel recommends against cefepime for serious or bloodstream infections and pyelonephritis/cUTI, although…
If cefepime is started as empiric therapy for uncomplicated cystitis caused by an organism later identified as ESBL and clinical improvement occurs, no change or extension in antibiotic therapy is necessary

Data comparing cefepime vs carbapenem for ESBL infections have mixed results
- - Seo YB, Lee J, Kim YK, et al. Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli. BMC Infect Dis 2017; 17(1): 404.
    - Clinical trial evaluating treatment of confirmed ESBL pyelonephritis and cUTI was terminated early for high clinical failure signal with cefepime (despite all isolates having cefepime MICs of 1-2)
  - Kim SA, Altshuler J, Paris D, Fedorenko M. Cefepime versus carbapenems for the treatment of urinary tract infections caused by extended-spectrum β-lactamase-producing enterobacteriaceae. Int J Antimicrob Agents. 2018;51(1):155-158. doi:10.1016/j.ijantimicag.2017.09.013
  - Observational studies have demonstrated either no difference or poorer outcomes with cefepime

Approaching cefepime MICs when thinking about ampC/ESBL infections

Enterobacterales isolates exhibiting cefepime MICs of 4-8 µg/mL (i.e., susceptible dose-dependent) may have higher likelihood of co-producing ESBLs compared to isolates with lower cefepime MICs
- - Pranita discussed a study from Taiwan that showed E.cloacae isolates with MICs 4-8 were more likely to be ESBL-producing and has poorer clinical outcomes: Lee NY, Lee CC, Li CW, et al. Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates. Antimicrob Agents Chemother. 2015;59(12):7558-7563. doi:10.1128/AAC.01477-15
    - - Evaluated 217 patients with E.cloacae bloodstream infection
      - 89% of E.cloacae isolates with cefepime MICs of 4-8 were ESBL-producing
      - Also found that all 10 patients with infections caused by ESBL-producing isolates with cefepime MICs of 4-8 who received cefepime died within 30 days. In contrast, none of the 6 patients who received cefepime for non-ESBL-producing isolates with MICs of 4-8 died within 30 days
Another small, single center US study also suggested that the likelihood of ESBL production increases in E.cloacae as cefepime MICs increase: Szabo D, Bonomo RA, Silveira F, et al. SHV-type extended-spectrum beta-lactamase production is associated with Reduced cefepime susceptibility in Enterobacter cloacae. J Clin Microbiol 2005; 43(10): 5058-64.
A different study though found that there was no difference in patients with bacteremia with these organisms treated with high dose cefepime vs carbapenems, although it’s not totally clear what the prevalence of ESBL production was: Kunz Coyne AJ, El Ghali A, Lucas K, et al. High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC β-lactamase Production. Open Forum Infect Dis. 2023;10(3):ofad034. Published 2023 Jan 25. doi:10.1093/ofid/ofad034

Episode Art & Infographics

Infographics

Find all the Febrile infographics here!

Goal

Listeners will be able to discuss management of serious AmpC and extended-spectrum beta-lactamase (ESBL) infections

Learning Objectives

After listening to this episode, listeners will be able to:

Identify the Enterobacterales spp considered at moderate to high risk for clinically significant AmpC production due to an inducible ampC gene (Enterobacter cloacae, Klebsiella aerogenes, Citrobacter freundii)
Understand the current IDSA guidance for treatment regimens for AmpC and ESBL infections
Discuss the use of cefepime and piperacillin-tazobactam for AmpC and ESBL infections

Disclosures

Our guest (Pranita Tamma) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Tamma, P., Al-Lawati, H., Dong, S. “#76: Pièce de (Gram-negative) Resistance, Part 1: AmpC, ESBL”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/1065b5a4-5a45-4ae2-a67c-5496071da703

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