Dataset Information

Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance.

ABSTRACT:

Background

To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals.

Methods

Three hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing isolates. Susceptibility testing was performed by broth microdilution, and minimum inhibitory concentrations (MICs) interpreted per EUCAST breakpoints. Carbapenemase-, aminoglycoside modifying enzyme- and 16S rRNA methylase- encoding genes were detected by PCR.

Results

Of 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at ?2?mg/L, with MIC₅₀/MIC₉₀ of 0.5/4?mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at ?8?mg/L and was the second most active drug after plazomicin, followed by gentamicin (S, 43%; MIC₅₀/MIC₉₀, 4/>?256) and amikacin (S, 18.0%; MIC₅₀/MIC₉₀, 32/128). Twenty-three (7.7%) isolates (16 KPC-, 6 VIM- and one KPC & OXA-48-producers) exhibited MICs ?64?mg/L for plazomicin, and harbored rmtB (n =?22) or armA (n =?1). AAC(6')-?b was the most common aminoglycoside modifying enzyme (84.7%), followed by AAC(3?)-IIa (25.3%), while those two enzymes were co-produced by 21.4% of the isolates.

Conclusions

Plazomicin retains activity against most carbapenemase-producing K. pneumoniae isolated from Greek hospitals, with MICs consistently lower than those of the other aminoglycosides, even in the presence of aminoglycoside modifying enzymes. Dissemination of 16S- rRNA methylases in 8% of the isolates is an unwelcome event that needs strict infection control measures and rigorous stewardship interventions.

SUBMITTER: Galani I

PROVIDER: S-EPMC6377745 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance.

Galani Irene I Nafplioti Konstantina K Adamou Panagiota P Karaiskos Ilias I Giamarellou Helen H Souli Maria M

BMC infectious diseases 20190215 1

<h4>Background</h4>To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals.<h4>Methods</h4>Three hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing ...[more]

PMID: 30770727

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Project description:Background: The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses an immediate threat to treatment worldwide. This retrospective study assessed the molecular epidemiology and determined the risk factors for and outcomes of CRKP infections in a general teaching hospital in Shanghai, China. Methods: From January 2013 to July 2015, 100 consecutive unique CRKP isolates isolated from hospitalized patients were collected. Isolates were screened for antibiotic resistance genes by polymerase chain reaction and molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Patients infected with CRKP comprised the case group and were compared to the control group of patients infected with carbapenem-susceptible Klebsiella pneumoniae. Therapeutic effects were compared in the CRKP infection group. Results: Among the 100 CRKP isolates, the percentages of multidrug-resistant, extensively drug-resistant (XDR), and pandrug-resistant were 50.0, 50.0, and 0%, respectively. All the CRKP isolates produced KPC-2 and could be divided into 18 PFGE clusters (A-O) and 70 subtypes. No dominant intra-hospital PFGE type was detected using a cutoff of 80% similarity. The ratio of CRKP infection to colonization was 51 to 49. Risk factors correlated with CRKP infection included pulmonary disease (p = 0.038), ICU stay (p = 0.002), invasive ventilation (p = 0.009), blood transfusion (p = 0.028), parenteral nutrition (p = 0.004), sputum suction (p = 0.006), medical history of previous hospitalization (p = 0.022), exposure to antibiotics 90 days before infection (p = 0.030), and antibiotic exposure during hospital stay including carbapenems (p = 0.013), enzyme inhibitors (p = 0.021), nitroimidazoles (p = 0.029), and glycopeptides (p = 0.000). Multivariable analysis showed that sputum suction (odds ratio 3.090, 95% confidence intervals 1.004-9.518, p = 0.049) was an independent risk factor for CRKP infections. Patients infected with CRKP with longer carbapenems treatment course (p = 0.002) showed better outcome. Conclusion: This study showed the severity of CRKP infection in eastern China. Sputum suction was an independent risk factor for CRKP infection. Prolonged duration of treatment with carbapenems benefited the patients infected with CRKP.

Project description:Carbapenem-resistantKlebsiella pneumoniae(CR-Kp) is significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract, where the bacterium is usually present at low density, but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood. Nevertheless, gaining such knowledge could lead to innovative intervention strategies for addressing colonization and infection. Here, we adopted anin vivomodel to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis, and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, the concentration of oxidative species and amino acids was increased in the mouse intestine following treatment. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were particularly upregulated, however their deletion did not impair CR-Kp fitness in vivoupon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein CRP as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, CRP deletion in CR-Kp resulted in strongly impaired gut colonization, but this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance towards bacterial fitness remains cryptic. Further analyses utilizing this model may identify key factors to tackle the intestinal stage of CR-Kp colonization.

Dataset Information

Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance.

Background

Methods

Results

Conclusions

Publications

Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance.

Similar Datasets

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