Abstract
BackgroundTo 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.MethodsThree 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.ResultsOf 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′)-Іb 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.ConclusionsPlazomicin 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.
Highlights
We evaluated the in vitro activities of plazomicin and comparator aminoglycosides and elucidated the underlying aminoglycoside resistance mechanisms among 300 carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals
The highest resistance rates were observed for tobramycin, with 89 and 83.3% resistant according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) breakpoints, and netilmicin, with 87.3 and 84.3% respectively
Plazomicin was active against most of the contemporary carbapenemase-producing K. pneumoniae isolates collected from 14 Greek hospitals, with 87.0% of the isolates inhibited by an Minimum inhibitor concentration (MIC)≤2 mg/L, while 94.2% of the isolates that did not carry a 16S rRNA methyltransferases (RMT) gene were inhibited by an MIC≤2 mg/L
Summary
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. The current epidemiology of carbapenemase-producing K. pneumoniae in Europe has been reported by Grundmann et al, as part of the European Survey on carbapenemase - producing Enterobacteriaceae (EuSCAPE) conducted from November 2013 till April 2014 in 35 European countries [4] According to this survey, an average of 1.3 patients per 10,000 hospital admissions in Europe had a carbapenemaseproducing K. pneumoniae or E. coli infection, while this incidence in Greece was 5.78, the second highest behind Italy (5.96) [4]. An average of 1.3 patients per 10,000 hospital admissions in Europe had a carbapenemaseproducing K. pneumoniae or E. coli infection, while this incidence in Greece was 5.78, the second highest behind Italy (5.96) [4] In this survey, among 86 carbapenem-non-susceptible K. pneumoniae isolates from Greece, a large proportion -were KPC-positive (65%), followed by NDM (14%), VIM (11%) and OXA-48-positive (2%) [4]. In a recent multi-center study published by our group, among 394 carbapenem-resistant K. pneumoniae isolates from 15 Greek hospitals 66.5% were KPC-, 13.7% were NDM-, 8.6% were VIM-, 5.6% were KPC and VIMand 3.6% were OXA-48-producers [5]
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