Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries

Castanheira, Mariana; Deshpande, Lalitagauri M.; Costello, Andrew J.; Davies, Todd A.; Jones, Ronald N.

doi:10.1093/jac/dku048

Cited by 184 publications

(145 citation statements)

References 26 publications

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“…Increasing prevalences of KPC-Kp and metallo-b-lactamase (MBL)-producing P. aeruginosa, for example, were reported in various European and Mediterranean countries. 46 KPC genes were…”

Section: Discussionmentioning

confidence: 99%

Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis

Righi

Peri

Harris

et al. 2016

J. Antimicrob. Chemother.

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Background: Carbapenem-resistant Gram-negative bacteria are recognized as a cause of difficult-to-treat infections associated with high mortality.Objectives: To perform a systematic review of currently available data on distribution, characteristics and outcome associated with carbapenem-resistant bloodstream infections in adult neutropenic patients.Methods: Included studies were identified through Medline, Embase and Cochrane databases between January 1995 and April 2016. Random effect meta-analysis was used to quantify the association between carbapenem resistance and mortality and between carbapenem exposure and resistance.Results: A total of 30 studies from 21 countries were included. Overall carbapenem resistance varied from 2% to 53% (median 9%) among studies. Infections due to carbapenem-resistant Pseudomonas spp. were reported in 18 (60%) studies showing high median resistance rates (44% of all carbapenem-resistant Gram-negatives and 19% of Pseudomonas isolates). Resistance of Enterobacteriaceae was less commonly reported and bloodstream infections due to carbapenem-resistant Klebsiella spp. were mainly documented from endemic areas (Greece, Italy, Israel). Carbapenem resistance in Acinetobacter spp. was reported in 9 (30%) studies (median resistance 58% of Acinetobacter isolates). Mortality rates ranged from 33% to 71% (median 50%) in patients with carbapenem-resistant infections. Carbapenem resistance appeared to correlate with mortality (OR 4.89,) and previous exposure to carbapenems (OR 4.63,.Conclusions: Carbapenem resistance represents a threat to neutropenic patients. In this group, resistance is likely promoted by previous carbapenem use and leads to high mortality rates. The knowledge of resistance patterns is crucial and can direct clinicians in the use of alternatives to carbapenem-based regimens.

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“…Increasing prevalences of KPC-Kp and metallo-b-lactamase (MBL)-producing P. aeruginosa, for example, were reported in various European and Mediterranean countries. 46 KPC genes were…”

Section: Discussionmentioning

confidence: 99%

Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis

Righi

Peri

Harris

et al. 2016

J. Antimicrob. Chemother.

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“…RNA extraction and treatment and relative quantification of target genes were performed as previously described (19). Endogenous reference genes (rspL for E. cloacae and gyrA for K. pneumoniae) and custom-designed primers showing efficiencies of Ͼ95.0% were used.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Clonality and Carbapenem Resistance Mechanisms among Acinetobacter baumannii-Acinetobacter calcoaceticus Complex and Enterobacteriaceae Isolates Collected in European and Mediterranean Countries and Detection of Two Novel β-Lactamases, GES-22 and VIM-35

Castanheira

Costello

Woosley

et al. 2014

Antimicrob Agents Chemother

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We evaluated doripenem-resistant Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ACB; n ‫؍‬ 411) and Enterobacteriaceae (n ‫؍‬ 92) isolates collected from patients from 14 European and Mediterranean countries during 2009 to 2011 for the presence of carbapenemase-encoding genes and clonality. Following susceptibility testing, carbapenem-resistant (doripenem MIC, >2 g/ml) isolates were screened for carbapenemases. New ␤-lactamase genes were expressed in a common background and susceptibility was tested. Class 1 integrons were sequenced. Clonality was evaluated by pulsed-field gel electrophoresis and multilocus sequence typing (Pasteur scheme). Relative expression of ␤-lactam intrinsic resistance mechanisms was determined for carbapenemase-negative Enterobacteriaceae. ACB and Enterobacteriaceae displayed 58.9 and 0.9% doripenem resistance, respectively. bla OXA-23 , bla OXA-58 , and bla OXA-24/OXA-40 were detected among 277, 77, and 29 ACB, respectively (in 8, 6, and 5 countries). Ten Turkish isolates carried bla GES-11 or bla GES-22 . GES-22 (G243A and M169L mutations in GES-1) had an extendedspectrum ␤-lactamase profile. A total of 33 clusters of >2 ACB isolates were observed, and 227 isolates belonged to sequence type 2/international clone II. Other international clones were limited to Turkey and Israel. Doripenem-resistant Enterobacteriaceae increased significantly (0.7 to 1.6%), and 15 bla KPC-2 -and 22 bla KPC-3 -carrying isolates, mostly belonging to clonal complexes 11 and 258, were observed. Enterobacteriaceae isolates producing OXA-48 (n ‫؍‬ 16; in Turkey and Italy), VIM-1 (n ‫؍‬ 10; in Greece, Poland, and Spain), VIM-26 (n ‫؍‬ 1; in Greece), and IMP-19, VIM-4, and the novel VIM-35 (n ‫؍‬ 1 each from Poland) were detected. VIM-35 had one substitution compared to VIM-1 (A235T) and a similar susceptibility profile. One or more resistance mechanisms were identified in 4/6 carbapenemase-negative Enterobacteriaceae. This broad evaluation confirms results from country-specific surveys and shows a highly diverse population of carbapenemase-producing ACB and Enterobacteriaceae in Europe and Mediterranean countries.

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“…A combination of resistance mechanisms is usually present [24] . In a recent study Castanheira et al [25] examined 529 carbapenem non-susceptible P.…”

Section: P Aeruginosamentioning

confidence: 99%

Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

Paramythiotou

Routsi

2016

WJCCM

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The incidence of gram-negative multidrug-resistant (MDR) bacterial pathogens is increasing in hospitals and particularly in the intensive care unit (ICU) setting. The clinical consequences of infections caused by MDR pathogens remain controversial. The purpose of this review is to summarize the available data concerning the impact of these infections on mortality in ICU patients. Twenty-four studies, conducted exclusively in ICU patients, were identified through PubMed search over the years 2000-2015. Bloodstream infection was the only infection examined in eight studies, respiratory infections in four and variable infections in others. Comparative data on the appropriateness of empirical antibiotic treatment were provided by only seven studies. In ten studies the presence of antimicrobial resistance was not associated with increased mortality; on the contrary, in other studies a significant impact of antibiotic resistance on mortality was found, though, sometimes, mediated by inappropriate antimicrobial treatment. Therefore, a direct association between infections due to gram-negative MDR bacteria and mortality in ICU patients cannot be confirmed. Sample size, presence of multiple confounders and other methodological issues may influence the results. These data support the need for further studies to elucidate the real impact of infections caused by resistant bacteria in ICU patients.

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Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries

Abstract: Increasing MβL prevalence is worrisome in various European countries; however, intrinsic resistance mechanisms in a highly genetically diverse population of carbapenem-non-susceptible P. aeruginosa are probably a matter for greater concern in these countries.

Cited by 184 publications

References 26 publications

Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis

Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis

Evaluation of Clonality and Carbapenem Resistance Mechanisms among Acinetobacter baumannii-Acinetobacter calcoaceticus Complex and Enterobacteriaceae Isolates Collected in European and Mediterranean Countries and Detection of Two Novel β-Lactamases, GES-22 and VIM-35

Association between infections caused by multidrug-resistant gram-negative bacteria and mortality in critically ill patients

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