Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

Abstract

Therapy of invasive infections due to multidrug-resistant (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing (CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.

Epidemiology of and risk factors for infection with extended-spectrum β-lactamase-producing carbapenem-resistant Enterobacteriaceae: results of a double case–control study

“…Patients at high risk for ESBL-producing infections often experience greater mortality, longer hospitalization, and higher costs of treatment 3,4. Carbapenems, potent antibiotics used in treating Gram-negative bacilli infections, are frequently used for suspected or diagnosed infections caused by ESBL-producing bacteria 5. With the increased utility of carbapenem driven by the dissemination of ESBL-producing Enterobacteriaceae , carbapenem-resistant Enterobacteriaceae (CRE) have emerged over the past decade 6.…”

The Burden of Antimicrobial Resistance among Urinary Tract Isolates of Escherichia coli in the United States in 2017

“…The increase in resistance to many of the currently available oral options makes the management of 266 that are prevalent among common Gram-negative UTI pathogens [31]. 280…”

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

“…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 . Judicious use of carbapenems has now become mandatory following the emergence of carbapenem‐resistant Enterobacteriaceae, caused by overuse of the drug . Non‐carbapenem treatment options against ESBL‐producing Enterobacteriaceae are being explored in order to spare carbapenem use.…”

“…1,12,13 Judicious use of carbapenems has now become mandatory following the emergence of carbapenem-resistant Enterobacteriaceae, caused by overuse of the drug. 2,3,7,14 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.…”