The Use of Noncarbapenem β-Lactams for the Treatment of Extended-Spectrum β-Lactamase Infections

Abstract

The continued rise in infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is recognized globally as one of the most pressing concerns facing the healthcare community. Carbapenems are widely regarded as the antibiotics of choice for the treatment of ESBL-producing infections, even when in vitro activity to other β-lactams has been demonstrated. However, indiscriminant carbapenem use is not without consequence, and carbapenem overuse has contributed to the emergence of carbapenem-resistant Enterobacteriaceae. The use of non-carbapenem β-lactams for the treatment of ESBL infections has yielded conflicting results. In this review, we discuss the available data for the use of cephamycins, cefepime, piperacillin-tazobactam, ceftolozane-tazobactam, and ceftazidime-avibactam for the treatment of ESBL infections.

Multicenter Evaluation of the New Etest Gradient Diffusion Method for Piperacillin-Tazobactam Susceptibility Testing of Enterobacterales , Pseudomonas aeruginosa , and Acinetobacter baumannii Complex

“…Tazobactam, a penicillanic acid ␤-lactamase inhibitor, protects the activity of piperacillin against Gram-negative isolates producing narrow-spectrum or some extended-spectrum ␤-lactamases (ESBL) (1)(2)(3). Due to the worldwide dispersion of ESBL producers, piperacillin-tazobactam has been viewed as a carbapenem-sparing option (4)(5)(6), although controversial reports have also been reported (7,8).…”

Cefmetazole for extended‐spectrum β‐lactamase‐producing Enterobacteriaceae in pediatric pyelonephritis

“…Cephamycins that are currently on the market are cefoxitin, cefotetan, cefmetazole, flomoxef, and moxalactam . According to early anecdotal reports, however, ESBL‐producing Enterobacteriaceae may develop resistance to cephamycin antibiotics during treatment via ompR mutations causing a porin deficiency, and by the acquisition of plasmid‐mediated AmpC , but the frequency of resistance acquisition is still unknown …”

“…Non‐carbapenem treatment options against ESBL‐producing Enterobacteriaceae are being explored in order to spare carbapenem use. As an example, piperacillin/tazobactam was reported to be potentially effective in treating infection caused by ESBL‐producing Enterobacteriaceae in adults . In severe ESBL‐producing bacterial infection, however, piperacillin/tazobactam is not generally recommended due to the higher mortality rate associated with its use .…”

“…5 According to early anecdotal reports, however, ESBL-producing Enterobacteriaceae may develop resistance to cephamycin antibiotics during treatment via ompR mutations causing a porin deficiency, and by the acquisition of plasmidmediated AmpC, but the frequency of resistance acquisition is still unknown. 2,[6][7][8][9][10][11] The WHO has also urgently declared the need for new antibiotics to counter the threat posed by carbapenem-resistant Enterobacteriaceae and by Pseudomonas aeruginosa as carbapenem-resistant Gram-negative rod (GNR) bacteria. 1,12,13 Judicious use of carbapenems has now become mandatory following the emergence of carbapenem-resistant Enterobacteriaceae, caused by overuse of the drug.…”

“…As an example, piperacillin/tazobactam was reported to be potentially effective in treating infection caused by ESBL-producing Enterobacteriaceae in adults. 2,3,6,15 In severe ESBL-producing bacterial infection, however, piperacillin/tazobactam is not generally recommended due to the higher mortality rate associated with its use. 16 In Japan, cefmetazole and flomoxef are commercially available cephamycins and are used commonly.…”