Escalating antimicrobial resistance among Enterobacteriaceae: focus on carbapenemases

Abstract

aminoglycosides (AG); antimicrobial resistance (AMR); -lactamase inhibitors (BLI); blood stream infections (BSIs) ; carbapenem (CP); carbapenemase (CPase); carbapenem-resistant (CR); carbapenemresistant Enterobacterales (CRE) ;-lactam inhibitor (BLI); CP-resistant K. pneumoniae (CRKP); CPsusceptible K. pneumoniae (CSKP); ceftazidime/avibactam (CAZ-AVI); cephalosporins (CEPHS); central line-associated (CLA); central venous catheter (CVC); community-acquired infection (CAI); complicated intra-abdominal infection (c-IAI); complicated urinary tract infection (c-UTI); defined daily dose (DDD) ; extended-spectrum -lactamases (ESBLs); extensively Drug Resistant (eXDR); fluoroquinolones (FQ); Gram negative bacteria (GNB); gross domestic product per capita (GDPPC); high-income countries (HICs); hospital acquired infection (HAI); imipenem-relebactam (IMI-REL); intensive care units (ICUs); Klebsiella pneumoniae carbapenemases (KPCs); long-term care facilities (LTCFs); low-and middleincome countries (LMICs); mechanical ventilation; metallo-lactamase (MBL); minimal inhibitory concentration (MIC); mobile genetic elements (MGEs); multidrug resistant (MDR); New Delhi Metalloproteinase-1 (NDM-1); non-Proteus Enterobacterales (NPE); organ transplant recipients (OTR); piperacillin/tazobactam (PTZ); solid organ transplant (SOT); tigecycline (TGC); ventilator-associated pneumonia (VAP)

Activity of cefepime/taniborbactam and comparators against whole genome sequenced ertapenem-non-susceptible Enterobacterales clinical isolates: CANWARD 2007–19

“…Carbapenems such as ertapenem, imipenem, meropenem and doripenem are used both empirically and as directed therapy for infections caused by resistant and MDR pathogens including Enterobacterales. 1–5 Carbapenems and β-lactam/β-lactamase inhibitors are viewed as effective therapies for infections caused by MDR Enterobacterales. 1 , 2 , 6 However, as carbapenem non-susceptibility increases, clinicians/researchers are seeking carbapenem-sparing regimens such as novel β-lactam/β-lactamase inhibitors (including ceftazidime/avibactam and ceftolozane/tazobactam).…”

“… 1–5 Carbapenems and β-lactam/β-lactamase inhibitors are viewed as effective therapies for infections caused by MDR Enterobacterales. 1 , 2 , 6 However, as carbapenem non-susceptibility increases, clinicians/researchers are seeking carbapenem-sparing regimens such as novel β-lactam/β-lactamase inhibitors (including ceftazidime/avibactam and ceftolozane/tazobactam). 1 , 2 , 6 , 7 There is an unmet need for novel carbapenem-sparing β-lactam/β-lactamase inhibitors to treat infections caused by MDR Gram-negative bacilli including carbapenem-non-susceptible Enterobacterales.…”

Pseudomonas aeruginosa Pneumonia: Evolution of Antimicrobial Resistance and Implications for Therapy

“…266 Group 3 enzymes (class B) contain zinc in their active site, are potent hydrolyzers of CPs, and are not inhibited by β-lactamase inhibitors (BLI). 267 ESBLs, initially described in Enterobacteriaceae in the 1980s, 270 spread to PA beginning in the 1990s. 144,145 ESBLs hydrolyze late generation CEPHs and antipseudomonal penicillins, but do not affect CPs.…”

“…144,145 ESBLs hydrolyze late generation CEPHs and antipseudomonal penicillins, but do not affect CPs. 270 ESBLs encoded in PA include class A (e.g., PER, VIM, GES, KPC, BEL, PME) and class D (e.g., oxacillinase [OXA]) enzymes. 144 ESBLs comprising TEM, SHV, or cefotaximase (CTX-M) enzymes are common among Enterobacteriaceae but are occasionally detected only in PA. 144,230 Clonal dissemination of ESBLs within and between countries has driven AMR globally.…”

Extended Spectrum- and Carbapenemase-Based β-Lactam Resistance in the Arabian Peninsula—A Descriptive Review of Recent Years

“…The consequence of the increasing resistance to cephalosporins has been a worldwide surge in the use of carbapenem antibiotics (originally effective against ESBL-positive bacteria). This phenomenon, in turn, is leading to the global and regional emergence and spread of carbapenem-resistant bacteria (mainly Enterobacteriaceae ), potentially representing another formidable threat to public health [ 7 , 8 , 9 , 10 ]. Currently, carbapenem antibiotics, such as imipenem, ertapenem, meropenem, and doripenem, have a broad spectrum of activity and are crucial for treating life-threatening nosocomial (hospital-acquired) ESBL and MDR infections.…”