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Are New β-Lactam/β-Lactamase Inhibitors Viable Carbapenem Sparing Options for Treating Serious Infections Caused by Extended-Spectrum β-Lactamase-Producing Microorganisms?

Kallstrom, George, PhD Written as an editorial commentary regarding Hatem Amer et al. Comparative Study Between β-Lactam/β-Lactamase Inhibitors as Alternatives for Carbapenems in the Treatment of Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae pages 138–142 of the Journal.

Infectious Diseases in Clinical Practice: May 2019 - Volume 27 - Issue 3 - p 121–122
doi: 10.1097/IPC.0000000000000729
Editorial Comment

From the Summa Health System, Akron; and Department of Pathology, Northeast Ohio Medical University, Rootstown, OH.

Correspondence to: George Kallstrom, PhD, Summa Health System, 525 East Market St, Akron, OH 44304. E-mail:

The author has no funding or conflicts of interest to disclose.

The article “Comparative Study between β-Lactam/β-Lactamase Inhibitors as Alternatives for Carbapenems in the Treatment of Extended-Spectrum β-Lactamase (ESBL)-Producing Enterobacteriaceae” describes a preliminary region–focused study of newer combinations of β-lactam/β-lactamase inhibitors as an alternative to carbapenem therapy for treatment of infections caused by ESBL-producing Escherichia coli and Klebsiella spp.1 Clinical and Laboratory Standards Institute lowered cephalosporin breakpoints in 2010 and recommends reporting ESBL organisms as tested and not overriding cephalosporin results to resistant as had been common practice before 2010. Current Clinical and Laboratory Standards Institute guidelines do not recommend screening for ESBL-producing organisms for other than epidemiological purposes.2

Typically, ESBL-producing organisms will be nonsusceptible to first-generation cephalosporins and nonsusceptible to 1 or more of the third-generation cephalosporins. Previously, laboratories would screen for ESBL-producing organisms by incubating a third-generation cephalosporin with and without a β-lactamase inhibitor looking for a difference in minimum inhibitory concentration, as the β-lactam/β-lactamase combination would show increased susceptibility over the β-lactam alone, suggesting a (molecular class A) ESBL enzyme. Historically, carbapenems are preferable therapeutic antimicrobial agents for serious infections caused by ESBL-producing organisms, providing better clinical outcomes over third-generation cephalosporins or fluoroquinolones.3–6 The approach of reporting ESBLs as tested after lowering cephalosporin breakpoints is controversial as some third-generation cephalosporins are reported as susceptible in some ESBL-producing strains (particularly CTX-M–producing isolates).7 For this reason, many laboratories continue to screen for ESBL-producing strains, and many infectious disease physicians continue to use carbapenem therapy to treat serious infections caused by ESBL-producing organisms.

The newer β-lactam/β-lactamase inhibitors may be a viable alternative to carbapenems for treating ESBL infections. This study “Comparative Study between β-Lactam/β-Lactamase Inhibitors as Alternatives for Carbapenems in the Treatment of ESBL-Producing Enterobacteriaceae” is an encouraging preliminary study of in vitro data indicating that newer β-lactam/β-lactamase inhibitor combinations are potentially as effective as carbapenems therapy in vitro. More rigorous evaluations should be performed to include a broader study of newer β-lactam/β-lactamase inhibitor in vitro results and clinical outcomes data.

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1. Amer WH, Elshweikh SAR, Hablas NM. Comparative study between β-lactam/β-lactamase inhibitors as alternatives for carbapenems in the treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae. Inf Dis Clin Pract. 2019;27:138–142.
2. Dudley MN, Ambrose PG, Bhavnani SM, et al. Background and rationale for revised clinical and laboratory standards institute interpretive criteria (breakpoints) for Enterobacteriaceae and Pseudomonas aeruginosa: I. Cephalosporins and Aztreonam. Antimicrobial Susceptibility Testing Subcommittee of the Clinical and Laboratory Standards Institute. Clin Infect Dis. 2013;56(9):1301–1309.
3. Rodríguez-Baño J, Navarro MD, Romero L, et al. Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli in the CTX-M era: a new clinical challenge. Clin Infect Dis. 2006;43(11):1407–1414.
4. Rodríguez-Baño J, Picón E, Gijón P, et al. Community-onset bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: risk factors and prognosis. Clin Infect Dis. 2010;50(1):40–48.
5. McWilliams CS, Condon S, Schwartz RM, et al. Incidence of extended-spectrum-β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates that test susceptible to cephalosporins and aztreonam by the revised CLSI breakpoints. J Clin Microbiol. 2014;52(7):2653–2655.
6. Williamson DA, Roberts SA, Smith M, et al. High rates of susceptibility to ceftazidime among globally prevalent CTX-M-producing Escherichia coli: potential clinical implications of the revised CLSI interpretive criteria. Eur J Clin Microbiol Infect Dis. 2012;31(5):821–824.
7. Livermore DM, Andrews JM, Hawkey PM, et al. Are susceptibility tests enough, or should laboratories still seek ESBLs and carbapenemases directly? J Antimicrob Chemother. 2012;67:1569–1577.
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