&lt;p&gt;Efflux Pump AcrAB Confers Decreased Susceptibility to Piperacillin–Tazobactam and Ceftolozane–Tazobactam in Tigecycline-Non-Susceptible &lt;em&gt;Klebsiella pneumoniae&lt;/em&gt;&lt;/p&gt;

Li, Junjie; Xu, Qingqing; Ogurek, Sean; Li, Ziqiang; Wang, Peiyun; Quan, Xie; Sheng, Zhonghua; Wang, Minggui

doi:10.2147/idr.s279020

“…Piperacillin/tazobactam, ceftazidime, cefepime and carbapenem resistance in P. aeruginosa has been associated with ampC (PDC, Pseudomonas derived cephalosporinase) derepression, OprD loss (imipenem >meropenem), and/or hyperexpression of efflux pumps (meropenem, not imipenem) [13,28]. OprD porin loss and the majority of known efflux pumps do not alter ceftolozane/tazobactam MICs [13,18,28,29]. Rarely, P. aeruginosa may develop resistance to ceftolozane/tazobactam and ceftazidime/avibactam during treatment when an isolate acquires mutation(s) that highly de-repress expression of PDC [29,30].…”

Section: Discussionmentioning

confidence: 99%

Activity of ceftolozane/tazobactam against Gram-negative isolates among different infections in Hong Kong: SMART 2017–2019

Karlowsky

¹

,

Lob²,

Khan³

et al. 2022

Journal of Medical Microbiology

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Introduction. Ceftolozane/tazobactam was approved by the Drug Office, Department of Health, Government of the Hong Kong Special Administrative Region in 2017. Hypothesis/Gap Statement. Currently the in vitro activity of ceftolozane/tazobactam against Gram-negative pathogens isolated from patients in Hong Kong is undocumented. It would be prudent to document the activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and Enterobacterales isolated from hospitalized patients in Hong Kong. Aim. To describe the in vitro susceptibility of recent clinical isolates of P. aeruginosa and the two most common Enterobacterales species ( Klebsiella pneumoniae , Escherichia coli ) cultured from respiratory tract, intra-abdominal, urinary tract and bloodstream infection samples to ceftolozane/tazobactam and other commonly used antimicrobial agents. Methodology. CLSI-defined broth microdilution MICs were determined and interpreted for Gram-negative isolates collected in Hong Kong from 2017 to 2019 by the SMART surveillance programme. Results. For P. aeruginosa , 96.7 % of isolates (n=210) were susceptible to ceftolozane/tazobactam, while susceptibility rates were ≥14 % lower to meropenem (82.9 % susceptible), cefepime (82.4 %), ceftazidime (81.4 %), piperacillin/tazobactam (76.7 %) and levofloxacin (79.5 %). Ceftolozane/tazobactam inhibited 85.7 % of piperacillin/tazobactam-nonsusceptible isolates, 80.6–82.1 % of cefepime-, ceftazidime- or meropenem-nonsusceptible isolates, and 75.9 % of multidrug-resistant (MDR) isolates of P. aeruginosa . For K. pneumoniae , 96.1 % of isolates (n=308) were susceptible to ceftolozane/tazobactam compared with meropenem (99.0 % susceptible), piperacillin/tazobactam (93.8 %), cefepime (85.7 %) and ceftazidime (85.4 %). The majority (88.3 %) of ESBL (extended-spectrum β-lactamase) non-CRE (carbapenem-resistant Enterobacterales) phenotype isolates of K. pneumoniae were susceptible to ceftolozane/tazobactam, comparable to piperacillin/tazobactam (85.0 %) but lower than meropenem (100 %). For E. coli , 98.5 % of isolates (n=609) were susceptible to ceftolozane/tazobactam compared to meropenem (99.3 % susceptible), piperacillin/tazobactam (96.7 %), ceftazidime (82.3 %) and cefepime (76.5 %). The majority (96.7 %) of ESBL non-CRE phenotype isolates of E. coli were susceptible to ceftolozane/tazobactam, similar to both meropenem (100 %) and piperacillin/tazobactam (94.5 %). Conclusions. Overall, >96 % of clinical isolates of P. aeruginosa , K. pneumoniae and E. coli collected in Hong Kong in 2017–2019 were susceptible to ceftolozane/tazobactam, while the activity of several commonly prescribed β-lactams was reduced, especially for P. aeruginosa . Continued surveillance of ceftolozane/tazobactam and other agents is warranted.

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“…The major genetic regulators of these two pumps are RamA and RarA, respectively, together belonging to the AraC-type transcriptional regulators in K. pneumoniae , [ 46 , 47 ]. AcrAB is involved in the efflux of various antibiotics including the most recent broad-spectrum antibiotics, such as piperatazocillin or ceftolozane-tazobactam, and OqxAB expels fluoroquinolones, tigecyclin and nitrofurantoin [ 45 ]. Concerning the detection of efflux mechanisms and their prevalence in the resistance of clinical strains, Kareem et al showed that 27 of the 43 selected MDR K. pneumoniae clinical strains presented an efflux activity by using an EtBr-agar cartwheel screening method [ 48 ].…”

Section: Clinical Impact Situationmentioning

confidence: 99%

“…The oqxAB operon was originally described on plasmid carried by an E. coli strain conferring resistance to chloramphenicol and quinolones [44]. In K. pneumoniae, it is associated with the resistance of quinoxalines, quinolones, tigecycline, nitrofurantin and chloramphenicol [45]. The major genetic regulators of these two pumps are RamA and RarA, respectively, together belonging to the AraC-type transcriptional regulators in K. pneumoniae, [46,47].…”

Section: Enterobacteriaceaementioning

confidence: 99%

Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria

Davin-Régli

¹

,

Pagès

²

,

Ferrand

³

2021

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Antibiotic efflux is a mechanism that is well-documented in the phenotype of multidrug resistance in bacteria. Efflux is considered as an early facilitating mechanism in the bacterial adaptation face to the concentration of antibiotics at the infectious site, which is involved in the acquirement of complementary efficient mechanisms, such as enzymatic resistance or target mutation. Various efflux pumps have been described in the Gram-negative bacteria most often encountered in infectious diseases and, in healthcare-associated infections. Some are more often involved than others and expel virtually all families of antibiotics and antibacterials. Numerous studies report the contribution of these pumps in resistant strains previously identified from their phenotypes. The authors characterize the pumps involved, the facilitating antibiotics and those mainly concerned by the efflux. However, today no study describes a process for the real-time quantification of efflux in resistant clinical strains. It is currently necessary to have at hospital level a reliable and easy method to quantify the efflux in routine and contribute to a rational choice of antibiotics. This review provides a recent overview of the prevalence of the main efflux pumps observed in clinical practice and provides an idea of the prevalence of this mechanism in the multidrug resistant Gram-negative bacteria. The development of a routine diagnostic tool is now an emergency need for the proper application of current recommendations regarding a rational use of antibiotics.

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“…aureus: USA300 genome GCA 000013465.1 [51] and the TW20 genome GCA 000027045.1 [52]. K. pneumoniae: GCF 000784945 [53], GCF 001952915 [54], GCF 003073315, GCF 003076555 [55], and GCF 011006575 [56].…”

Section: Data Availabilitymentioning

confidence: 99%

“…K. pneumoniae : GCF_000784945[53], GCF_001952915[54], GCF_003073315, GCF_003076555[55], and GCF_011006575[56].…”

Section: Data Availabilitymentioning

confidence: 99%

Minos: variant adjudication and joint genotyping of cohorts of bacterial genomes

Hunt

¹

,

Letcher

²

,

Malone

³

et al. 2021

Preprint

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Short-read variant calling for bacterial genomics is a mature field, and there are many widely-used software tools. Different underlying approaches (eg pileup, local or global assembly, paired-read use, haplotype use) lend each tool different strengths, especially when considering non-SNP (single nucleotide polymorphism) variation or potentially distant reference genomes. It would therefore be valuable to be able to integrate the results from multiple variant callers, using a robust statistical approach to "adjudicate" at loci where there is disagreement between callers. To this end, we present a tool, Minos, for variant adjudication by mapping reads to a genome graph of variant calls. Minos allows users to combine output from multiple variant callers without loss of precision. Minos also addresses a second problem of joint genotyping SNPs and indels in bacterial cohorts, which can also be framed as an adjudication problem. We benchmark on 62 samples from 3 species (Mycobacterium tuberculosis, Staphylococcus aureus, Klebsiella pneumoniae) and an outbreak of 385 M. tuberculosis samples. Finally, we joint genotype a large M. tuberculosis cohort (N≈15k) for which the rifampicin phenotype is known. We build a map of non-synonymous variants in the RRDR (rifampicin resistance determining region) of the rpoB gene and extend current knowledge relating RRDR SNPs to heterogeneity in rifampicin resistance levels. We replicate this finding in a second M. tuberculosis cohort (N≈13k). Minos is released under the MIT license, available at https://github.com/iqbal-lab-org/minos.

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<p>Efflux Pump AcrAB Confers Decreased Susceptibility to Piperacillin–Tazobactam and Ceftolozane–Tazobactam in Tigecycline-Non-Susceptible <em>Klebsiella pneumoniae</em></p>

Cited by 12 publications

References 37 publications

Activity of ceftolozane/tazobactam against Gram-negative isolates among different infections in Hong Kong: SMART 2017–2019

Activity of ceftolozane/tazobactam against Gram-negative isolates among different infections in Hong Kong: SMART 2017–2019

Clinical Status of Efflux Resistance Mechanisms in Gram-Negative Bacteria

Minos: variant adjudication and joint genotyping of cohorts of bacterial genomes

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