In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015–2016

Galani, Irene; Souli, María; Nafplioti, Konstantina; Adamou, Panagiora; Karaiskos, Ilias; Giamarellou, Helen; Antoniadou, Anastasia

doi:10.1007/s10096-019-03517-y

Cited by 36 publications

(23 citation statements)

References 15 publications

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“…In the current study, 98.5% of the KPC-Kp were susceptible to I/R, while the combination was inactive against OXA-48 and MBL producers. This is consistent with a previous Greek study of 295 KPC-producing K. pneumoniae collected in 2015-2016, which reported that I/R inhibited 98% of the isolates at ≤ 2 mg/L [33]. Likewise, Yang et al [34] demonstrated that relebactam had a high effect in restoring the susceptibilities of K. pneumoniae strains to imipenem, with reduced MIC values (up to 64-fold).…”

Section: Discussionsupporting

confidence: 90%

Epidemiology and in vitro activity of ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, plazomicin, and comparators against Greek carbapenemase-producing Klebsiella pneumoniae isolates

et al. 2021

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Background The increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is of great concern because of limited treatment options. New antimicrobials were recently approved for clinical therapy. This study evaluated the epidemiology of carbapenemase-producing K. pneumoniae isolates collected at a Greek university hospital during 2017-2020, and their susceptibilities to ceftazidime-avibactam (CAZ/AVI), meropenem-vaborbactam (M/V), imipenem-relebactam (I/R), eravacycline, plazomicin, and comparators. Methods Minimum inhibitory concentrations (MICs) were evaluated by Etest. Only colistin MICs were determined by the broth microdilution method. Carbapenemase genes were detected by PCR. Selected isolates were typed by multilocus sequence typing (MLST). Results A total of 266 carbapenemase-producing K. pneumoniae strains were isolated during the 4-year study period. Among them, KPC was the most prevalent (75.6%), followed by NDM (11.7%), VIM (5.6%), and OXA-48 (4.1%). KPC-producing isolates belonged mainly to ST258 and NDM producers belonged to ST11, whereas OXA-48-and VIM producers were polyclonal. Susceptibility to tigecycline, fosfomycin, and colistin was 80.5%, 83.8%, and 65.8%, respectively. Of the novel agents tested, plazomicin was the most active inhibiting 94% of the isolates at ≤ 1.5 μg/ml. CAZ/AVI and M/V inhibited all KPC producers and I/R 98.5% of them. All OXA-48 producers were susceptible to CAZ/AVI and plazomicin. The novel β-lactam/β-lactamase inhibitors (BLBLIs) tested were inactive against MBL-positive isolates, while eravacycline inhibited 61.3% and 66.7% of the NDM and VIM producers, respectively. Conclusions KPC remains the predominant carbapenemase among K. pneumoniae, followed by NDM. Novel BLBLIs, eravacycline, and plazomicin are promising agents for combating infections by carbapenemase-producing K. pneumoniae. However, the emergence of resistance to these agents highlights the need for continuous surveillance and application of enhanced antimicrobial stewardship.

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Section: Discussionsupporting

confidence: 90%

Epidemiology and in vitro activity of ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, plazomicin, and comparators against Greek carbapenemase-producing Klebsiella pneumoniae isolates

et al. 2021

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“…The antibacterial activities of fosfomycin and meropenem combination and colistin with meropenem combinations effective inhibited NDM and carbapenemase producing K. pneumoniae [34,39]. In addition, relebactam-imipenem combinations showed enhanced antibacterial activity against colistin resistant K. pneumoniae with potentials of restoring bacteria susceptibility to imipenem [40,41].…”

Section: Combination Of Colistin With Carbapenemsmentioning

confidence: 95%

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

et al. 2021

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Multidrug resistant Enterobacterales have become a serious global health problem, with extended hospital stay and increased mortality. Antibiotic monotherapy has been reported ineffective against most drug resistant bacteria including Klebsiella pneumoniae, thus encouraging the use of multidrug therapies as an alternative antibacterial strategy. The present works assessed the antibacterial activity of colistin against K. pneumoniae isolates. Resistant isolates were tested against 16 conventional antibiotics alone and in combination with colistin. The results revealed that all colistin resistant isolates demonstrated multidrug resistance against the tested antibiotics except amikacin. At sub-inhibitory concentrations, combinations of colistin with amikacin, or fosfomycin showed synergism against 72.72% (8 of 11 isolates). Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens.

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“…The isolate collection tested in this study was a reflection of our national CPE epidemiology and did not include any imipenem/relebactam resistant KPC-producing Enterobacteral which represents a limitation. Besides, the MALDI-TOF MS assay exclusively detects enzymatic carbapenem resistance but does not detect carbapenem resistance due to other mechanisms that can confer resistance as the OmpK35 disruption and/or mutated OmpK36 that have been described as chromosomal resistance in these isolates (Galani et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Rapid Detection of KPC-Producing Enterobacterales Susceptible to Imipenem/Relebactam by Using the MALDI-TOF MS MBT STAR-Carba IVD Assay

2020

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KPC-producing Enterobacterales represent a serious public health concern. Limited therapeutic options are available for treatment, however, the novel combination of imipenem/relebactam represents a promising alternative. To preserve the activity of this new antibiotic combination, only targeted treatments will be recommended, and rapid tests to detect susceptible bacteria are therefore urgently needed. Here, we propose a MALDI-TOF-based method using the MBT STAR-Carba IVD assay, Bruker Daltonik, to detect KPC-producing Enterobacterales susceptible to imipenem/relebactam in a random selection of 143 clinical isolates previous molecular characterized, carrying 97 bla KPC , 1 bla GES , 12bla VIM , 4bla IMP , 3bla NDM , and 26bla OXA−48−like . Species identification was confirmed by MALDI-TOF MS. The molecular characterization of the isolates was performed by the Xpert Carba-R Assay and the results were used as gold standard. Besides, all isolates were submitted to imipenem and imipenem/relebactam microdilution susceptibility testing. The assay showed an overall sensitivity and specificity to detect class A-producing Enterobacterales susceptible to imipenem/relebactam of 98% (96/98) and 93% (42/45), respectively. This MALDI-TOF-based methodology, with a turnaround time of less than 1 h, is a reliable test for detecting imipenem/relebactam activity and its inclusion in routine laboratory screening would facilitate the correct use of this new combination of antimicrobials as a targeted treatment.

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In vitro activity of imipenem-relebactam against non-MBL carbapenemase-producing Klebsiella pneumoniae isolated in Greek hospitals in 2015–2016

Cited by 36 publications

References 15 publications

Epidemiology and in vitro activity of ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, plazomicin, and comparators against Greek carbapenemase-producing Klebsiella pneumoniae isolates

Epidemiology and in vitro activity of ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, eravacycline, plazomicin, and comparators against Greek carbapenemase-producing Klebsiella pneumoniae isolates

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

Rapid Detection of KPC-Producing Enterobacterales Susceptible to Imipenem/Relebactam by Using the MALDI-TOF MS MBT STAR-Carba IVD Assay

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