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CON: Carbapenems are NOT necessary for all infections caused by ceftriaxone-resistant Enterobacterales.

ABSTRACT: Carbapenems are considered the drugs of choice for the treatment of serious infections caused by ceftriaxone-resistant Enterobacterales. However, because of the dramatic increase in carbapenem-resistant organisms worldwide, finding alternatives to carbapenems is a must. The potential options include β-lactam/β-lactamase inhibitor combinations, temocillin, cephamycins and some non-β-lactam drugs. The most controversial is piperacillin/tazobactam; the results of the MERINO trial are challenged because the isolates of patients with worse outcomes were frequently not susceptible to piperacillin/tazobactam when studied by reference methods, and also because the drug was not administered in extended infusion. Other potential options are briefly discussed. We conclude that carbapenems are not necessary for all patients with infections caused by ceftriaxone-resistant Enterobacterales.

SUBMITTER: Rodriguez-Bano J

PROVIDER: S-EPMC8210108 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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CON: Carbapenems are NOT necessary for all infections caused by ceftriaxone-resistant Enterobacterales.

Rodríguez-Baño Jesús J Gutiérrez-Gutiérrez Belén B Pascual Alvaro A

JAC-antimicrobial resistance 20210224 1

Carbapenems are considered the drugs of choice for the treatment of serious infections caused by ceftriaxone-resistant Enterobacterales. However, because of the dramatic increase in carbapenem-resistant organisms worldwide, finding alternatives to carbapenems is a must. The potential options include β-lactam/β-lactamase inhibitor combinations, temocillin, cephamycins and some non-β-lactam drugs. The most controversial is piperacillin/tazobactam; the results of the MERINO trial are challenged bec ...[more]

PMID: 34223064

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Project description:Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities. Whole-genome sequencing identified extended-spectrum β-lactamase (ESBL) and ampC genes both in bacterial chromosomes (c-ampC) and on plasmids (p-ampC). Mutations in promoter or attenuator regions of the Escherichia coli c-ampC gene (i.e., blaEC gene) with the potential to result in ampC derepression were investigated. The presence of ESBL or ampC genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and ampC genes. ESBL families were identified among 398 (80%) patients: blaCTX-M (n = 370), blaSHV (n = 17), blaOXY (n = 14), and blaVEB (n = 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following: E. coli (67%), Klebsiella pneumoniae (24%), Klebsiella oxytoca (4%), Proteus mirabilis (2%), Enterobacter cloacae complex (2%), Klebsiella aerogenes (1%), Providencia stuartii (<1%), and Serratia marcescens (<1%). c-ampC genes were identified in 374 (75%) of the 500 isolates. Only 7% of E. coli isolates with mutations in the promoter or attenuator region of the c-ampC gene exhibited resistance to cefoxitin, a proxy for increased AmpC production. Two p-ampC genes were confirmed in 25 (5%) of the 500 isolates: blaCMY-59 (72%) and blaDHA-1 (28%; confined to E. coli [92%] and K. pneumoniae [8%]). Until comprehensive β-lactamase molecular testing is available, the species-specific prevalence of ESBL and ampC genes in ceftriaxone-resistant Enterobacterales should be considered to promote effective albeit judicious antibiotic prescribing. Mutations in promoter or attenuator regions of the E. coli c-ampC gene do not appear to contribute significantly to increased AmpC production in this species.

Project description:BackgroundData on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials.MethodsAn international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors.FindingsOverall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-β-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results.InterpretationThe main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics.FundingThe study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).

Dataset Information

CON: Carbapenems are NOT necessary for all infections caused by ceftriaxone-resistant Enterobacterales.

Publications

CON: Carbapenems are NOT necessary for all infections caused by ceftriaxone-resistant Enterobacterales.

Similar Datasets

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