Dataset Information

Emergence of KPC-producing Klebsiella pneumoniae in Uruguay: infection control and molecular characterization.

ABSTRACT: We describe the first outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP), the infection control measures adopted and the shift in resistance patterns of isolates during antibiotic treatment. The ST258 KPC-KP strain exhibited a multiresistant antibiotic phenotype including co-resistance to gentamycin, colistin and tigecycline intermediate susceptibility. Isolates before and after treatment had different behaviour concerning their antibiotic susceptibility and the population analysis profile study. A progressive increase in the aminoglycosides (acquiring amicacin resistance) and ?-lactam MICs, and a decreased susceptibility to fosfomycin was observed throughout the administration of combined antimicrobial regimens including meropenem. A high meropenem resistance KPC-KP homogeneous population (MIC 256 Jg/mL), could arise from the meropenem heterogeneous low-level resistance KPC-KP population (MIC 8 Jg/mL), by the selective pressure of the prolonged meropenem therapy. The kpc gene was inserted in a Tn4401 isoform a, and no transconjugants were detected. The core measures adopted were successful to prevent evolution towards resistance dissemination.

SUBMITTER: Marquez C

PROVIDER: S-EPMC4184659 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Emergence of KPC-producing Klebsiella pneumoniae in Uruguay: infection control and molecular characterization.

Marquez C C Ingold A A Echeverría N N Acevedo A A Vignoli R R García-Fulgueiras V V Viroga J J Gonzalez O O Odizzio V V Etulain K K Nuñez E E Albornoz H H Borthagaray G G Galiana A A

New microbes and new infections 20140404 3

We describe the first outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP), the infection control measures adopted and the shift in resistance patterns of isolates during antibiotic treatment. The ST258 KPC-KP strain exhibited a multiresistant antibiotic phenotype including co-resistance to gentamycin, colistin and tigecycline intermediate susceptibility. Isolates before and after treatment had different behaviour concerning their antibiotic susceptibility and the pop ...[more]

PMID: 25356345

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Project description:Carbapenem-resistant Enterobacteriaceae (CRE) are resistant to most antibiotics, making CRE infections extremely difficult to treat with available agents. Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) are predominant carbapenemases in CRE in the United States. Nacubactam is a bridged diazabicyclooctane (DBO) β-lactamase inhibitor that inactivates class A and C β-lactamases and exhibits intrinsic antibiotic and β-lactam "enhancer" activity against Enterobacteriaceae In this study, we examined a collection of meropenem-resistant K. pneumoniae isolates carrying blaKPC-2 or blaKPC-3; meropenem-nacubactam restored susceptibility. Upon testing isogenic Escherichia coli strains producing KPC-2 variants with single-residue substitutions at important Ambler class A positions (K73, S130, R164, E166, N170, D179, K234, E276, etc.), the K234R variant increased the meropenem-nacubactam MIC compared to that for the strain producing KPC-2, without increasing the meropenem MIC. Correspondingly, nacubactam inhibited KPC-2 (apparent Ki [Ki app] = 31 ± 3 μM) more efficiently than the K234R variant (Ki app = 270 ± 27 μM) and displayed a faster acylation rate (k2/K), which was 5,815 ± 582 M-1 s-1 for KPC-2 versus 247 ± 25 M-1 s-1 for the K234R variant. Unlike avibactam, timed mass spectrometry revealed an intact sulfate on nacubactam and a novel peak (+337 Da) with the K234R variant. Molecular modeling of the K234R variant showed significant catalytic residue (i.e., S70, K73, and S130) rearrangements that likely interfere with nacubactam binding and acylation. Nacubactam's aminoethoxy tail formed unproductive interactions with the K234R variant's active site. Molecular modeling and docking observations were consistent with the results of biochemical analyses. Overall, the meropenem-nacubactam combination is effective against carbapenem-resistant K. pneumoniae Moreover, our data suggest that β-lactamase inhibition by nacubactam proceeds through an alternative mechanism compared to that for avibactam.

Dataset Information

Emergence of KPC-producing Klebsiella pneumoniae in Uruguay: infection control and molecular characterization.

Publications

Emergence of KPC-producing Klebsiella pneumoniae in Uruguay: infection control and molecular characterization.

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