Dataset Information

In Vitro Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli.

ABSTRACT: Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel ?-lactam-?-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring blaKPC (n = 110), the addition of relebactam to imipenem lowered the MIC50/MIC90 from 16/>128 ?g/ml for imipenem alone to 0.25/1 ?g/ml. For isolates harboring blaCTX-M (n = 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 ?g/ml (83% susceptible). For isolates harboring blaCMY-2 (n = 17), the MIC50/MIC90 of ceftolozane-tazobactam were 4/8 ?g/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) Enterobacteriaceae and is an encouraging addition to the present antibiotic repertoire.

SUBMITTER: Schmidt-Malan SM

PROVIDER: S-EPMC6105828 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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<i>In Vitro</i> Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli.

Schmidt-Malan Suzannah M SM Mishra Avisya J AJ Mushtaq Ammara A Brinkman Cassandra L CL Patel Robin R

Antimicrobial agents and chemotherapy 20180727 8

Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel β-lactam-β-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring <i>bla ...[more]

PMID: 29760145

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Project description:ObjectivesTo determine susceptibility profiles and β-lactamase content for ceftolozane/tazobactam-resistant and imipenem/relebactam-resistant Pseudomonas aeruginosa isolates collected in eight global regions during 2016-21.MethodsBroth microdilution MICs were interpreted using CLSI breakpoints. PCR to identify β-lactamase genes or WGS was performed on selected isolate subsets.ResultsCeftolozane/tazobactam-resistant [from 0.6% (Australia/New Zealand) to 16.7% (Eastern Europe)] and imipenem/relebactam-resistant [from 1.3% (Australia/New Zealand) to 13.6% (Latin America)] P. aeruginosa varied by geographical region. Globally, 5.9% of isolates were both ceftolozane/tazobactam resistant and imipenem/relebactam resistant; 76% of these isolates carried MBLs. Most ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible isolates carried ESBLs (44%) or did not carry non-intrinsic (acquired) β-lactamases (49%); 95% of imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible isolates did not carry non-intrinsic β-lactamases. Isolates that carried indicators of strong PDC (Pseudomonas-derived cephalosporinase) up-regulation without a mutation known to expand the spectrum of PDC, or non-intrinsic β-lactamases, showed an 8-fold increase in ceftolozane/tazobactam modal MIC; however, this rarely (3%) resulted in ceftolozane/tazobactam resistance. Isolates with a PDC mutation and an indicator for PDC upregulation were ceftolozane/tazobactam non-susceptible (MIC, ≥ 8 mg/L). MICs ranged widely (1 to >32 mg/L) for isolates with a PDC mutation and no positively identified indicator for PDC up-regulation. Imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible isolates without non-intrinsic β-lactamases frequently (91%) harboured genetic lesions implying OprD loss of function; however, this finding alone did not account for this phenotype. Among imipenem-non-susceptible isolates without non-intrinsic β-lactamases, implied OprD loss only shifted the distribution of imipenem/relebactam MICs up by 1-2 doubling dilutions, resulting in ∼10% imipenem/relebactam-resistant isolates.ConclusionsP. aeruginosa with ceftolozane/tazobactam-resistant/imipenem/relebactam-susceptible and imipenem/relebactam-resistant/ceftolozane/tazobactam-susceptible phenotypes were uncommon and harboured diverse resistance determinants.

Project description:Objectives:We investigated the in vitro antimicrobial susceptibilities of clinically important Gram-negative bacteria (GNB) from 16 major teaching hospitals in Taiwan in 2017. Materials and methods:Escherichia coli (n=686) and Klebsiella pneumoniae bloodstream isolates (n=673), non-typhoid Salmonella (NTS; n=221) from various sources, Shigella species (n=21) from fecal samples, and Neisseria gonorrhoeae (n=129) from the genitourinary tract were collected. Antibiotic minimum inhibitory concentrations (MICs) were determined using the broth microdilution method. Alleles encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-?-lactamases (NDMs), Verona integron-encoded metallo-?-lactamase, imipenemase, OXA-48-like, and mcr-1-5 genes were detected by molecular methods in Enterobacteriaceae isolates. Results:Five (0.7%) E. coli isolates harbored mcr-1 alleles. Twenty-four (3.6%), seven (1.0%), four (0.6%), and one (0.15%) K. pneumoniae isolates contained bla KPC, bla OXA-48-like, mcr-1, and bla NDM, respectively. Three (1.4%) NTS and no Shigella isolates harbored mcr-1 genes. Seventy-one (10.5%) K. pneumoniae isolates displayed non-susceptibility (NS) to carbapenem agent(s). Phenotypically extended-spectrum ?-lactamase (ESBL)-producing K. pneumoniae isolates showed significantly higher rates of ertapenem, tigecycline, and ceftolozane-tazobactam (CLZ- TAZ) NS (40.2%, 16.3%, and 71%-80%, respectively) than E. coli isolates exhibiting ESBL phenotypes (5.4%, 0.7%, and 18%-28%, respectively). All phenotypically ESBL-producing E. coli isolates were ceftazidime-avibactam (CAZ-AVB) susceptible. Two (8.3%) KPC-producing K. pneumoniae isolates showed CAZ-AVB NS. Hospital-acquired K. pneumoniae isolates were significantly less susceptible to ertapenem and CLZ-TAZ than hospital-acquired E. coli isolates. Conclusion:Third-generation cephalosporins remain the optimal choice for treating NTS, Shigella, and gonococcal infections in Taiwan. Hospital-acquired and phenotypically ESBL-producing K. pneumoniae are a heavy resistance burden in Taiwan.

Project description:Abstract Objectives To evaluate the in vitro activities of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Gram-negative bacilli collected in four central and northern European countries (Belgium, Norway, Sweden, Switzerland) during 2017–21. Methods Participating clinical laboratories each collected up to 250 consecutive Gram-negative isolates per year from patients with bloodstream, intraabdominal, lower respiratory tract or urinary tract infections. MICs were determined by CLSI broth microdilution and interpreted using 2022 EUCAST breakpoints. β-Lactamase genes were identified in select β-lactam-non-susceptible isolate subsets. Results Ninety-five percent of all Enterobacterales (n = 4158), 95% of ESBL-positive non-carbapenem-resistant Enterobacterales (non-CRE) phenotype Escherichia coli and 85% of ESBL-positive non-CRE phenotype Klebsiella pneumoniae were ceftolozane/tazobactam susceptible. By country, 88% (Belgium), 91% (Sweden, Switzerland) and 96% (Norway) of ESBL-positive non-CRE phenotype Enterobacterales were ceftolozane/tazobactam susceptible. Greater than ninety-nine percent of non-Morganellaceae Enterobacterales and all ESBL-positive non-CRE phenotype Enterobacterales were imipenem/relebactam susceptible. Ceftolozane/tazobactam (96%) and imipenem/relebactam (95%) inhibited most Pseudomonas aeruginosa (n = 823). Both agents retained activity against ≥75% of cefepime-resistant, ceftazidime-resistant and piperacillin/tazobactam-resistant isolates; 56% and 43% of meropenem-resistant isolates were ceftolozane/tazobactam susceptible and imipenem/relebactam susceptible, respectively. By country, 94% (Belgium), 95% (Sweden) and 100% (Norway, Switzerland) of P. aeruginosa were ceftolozane/tazobactam susceptible and 93% (Sweden) to 98% (Norway, Switzerland) were imipenem/relebactam susceptible. Carbapenemase gene carriage among Enterobacterales and P. aeruginosa isolates was generally low (<1%) or completely absent with one exception: an estimated 2.7% of P. aeruginosa isolates from Belgium carried an MBL. Conclusions Recent clinical isolates of Enterobacterales and P. aeruginosa collected in four central and northern European countries were highly susceptible (≥95%) to ceftolozane/tazobactam and imipenem/relebactam.

Dataset Information

In Vitro Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli.

Publications

<i>In Vitro</i> Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli.

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