Comparative Study Between β-Lactam/β-Lactamase Inhibitors as Alternatives for Carbapenems in the Treatment of Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae

Abstract

Background In the era of the increase in carbapenem resistance, searching for alternative drugs becomes mandatory. In this study, an in vitro activity of β-lactam/β-lactamase inhibitors against extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) isolated from bloodstream infections was investigated. Methods Blood samples were collected from patients with bloodstream infections in both pediatric and internal medicine intensive care units of Tanta University Hospitals, Egypt. BacT/ALERT was used, and positive blood cultures were subcultured on MacConkey, blood, chocolate agar and then incubated at 5% to 10% CO2, 37°C for 24 hours. Identification of the bacterial isolates was performed by VITEK 2TM Compact 15. Susceptibility testing was performed for isolated Escherichia coli and Klebsiella species using Kirby-Bauer disk diffusion and minimum inhibitory concentration. E test strips were used for cefoperazone/sulbactam, ceftazidime/avibactam, and ceftolozane/tazobactam. All isolates that were resistant to third-generation cephalosporins as per Clinical and Laboratory Standards Institute recommendations were confirmed for ESBL detection by modified double-disk synergy test, VITEK2 system, and multiplex polymerase chain reaction. Results One hundred twenty-five Enterobacteriaceae were isolated; 100 of them (80%) were ESBL positive. The best used β-lactam/β-lactamase inhibitors were ceftazidime/avibactam and ceftolozane/tazobactam with lower minimum inhibitory concentration at which 50% of isolates are inhibited (≤0.016, 0.094 μg/mL, respectively) than that of meropenem (0.125 μg/mL), so they can be used as carbapenem sparers in the treatment of ESBL-PE to decrease the incidence of carbapenem resistance. Conclusions Ceftazidime/avibactam and ceftolozane/tazobactam can be used as carbapenem sparers in the treatment of ESBL-PE to decrease the incidence of carbapenem resistance.

Global evaluation of the antibacterial activity of Ceftolozane/Tazobactam against ESBLs-producing Escherichia coli and Klebsiella pneumoniae: a systematic review and meta-analysis

“…Additionally, the MIC 90 values for both drugs were 0.25 µg/mL against ESBLs-EC and ESBLs-KP isolates. 4 The frequency of certain resistant strains and the activity of Ceftolozane-Tazobactam vary across high-risk patients, such as those aged >65 years, patients in intensive care units, and immunocompromised patients, as well as in different geographical regions. 22 Although Ceftolozane/Tazobactam is less effective than carbapenems against ESBLs-EC strains, it is essential to highlight that its use can help reduce carbapenem utilization and the emergence of carbapenem-resistant strains.…”

“…[1][2][3] Infections caused by ESBLs-producing Enterobacterales than comparable infections caused by non-ESBLs-producing bacteria are associated with lower therapeutic response, longer hospital stays, and more significant costs. 4,5 Carbapenems are widely recommended as a first-line drugs for treating serious invasive ESBLs-EC and ESBLs-KP infections. 6 However, the increase in carbapenems' use leads to the expansion of carbapenem-resistant and Carbapenemaseproducing Enterobacterales.…”

“…Therefore, for carbapenems conservative usage, it is necessary to use alternatives to carbapenems such as β-lactam/βlactamase inhibitors to treat infections caused by ESBLs-producing Enterobacterales. 4,5 Ceftolozane/Tazobactam is a β-lactam/β-lactamase inhibitor combination with a broad range of efficacy. It is active against Pseudomonas aeruginosa, many multidrug-resistant strains, and most ESBLsproducing Enterobacterales strains.…”

“…Therefore, for carbapenems conservative usage, it is necessary to use alternatives to carbapenems such as β-lactam/β-lactamase inhibitors to treat infections caused by ESBLs-producing Enterobacterales. 4,5…”