Carbapenem Non-susceptible Isolates Research Articles

In Vitro Susceptibility to Ceftazidime/Avibactam and Comparators in Clinical Isolates of Enterobacterales from Five Latin American Countries.

Background: High rates of resistance to third-generation cephalosporins and carbapenems in Enterobacterales have been reported in Latin America. Ceftazidime/avibactam (CZA) is the combination of a third-generation cephalosporin and a non-β-lactam β-lactamase inhibitor, which has shown activity against isolates producing class A, C and D β-lactamases. Herein, we evaluated the activity of CZA and comparators against clinical isolates of Enterobacterales in Latin America. Methods: The activity of CZA and comparators was evaluated against clinical isolates of Enterobacterales from Argentina, Brazil, Chile, Colombia and Mexico that were collected between January 2016 and October 2017. One specific phenotypic subset was evaluated. A carbapenem non-susceptible (CNS) phenotype was defined as any isolate displaying a minimum inhibitory concentration (MIC) ≥1 mg/L for ertapenem. Results: CZA was active against 95.8% of all isolates and 77.5% of CNS isolates. Fosfomycin (FOS) and tigecycline (TGC) were the second most active antibiotics with 93.4% of Enterobacterales being susceptible. Conclusions: The results of this study underline the potential therapeutic role of CZA in Latin America.

OXA-23 and OXA-40 producing carbapenem-resistant Acinetobacter baumannii in Central Illinois

We reviewed susceptibility of 840 A. baumannii complex isolates at two academic medical centers and explored their mechanism of carbapenem resistance. Carbapenem resistance rates among A. baumannii increased from <5% before 2005 to 55% in 2011 and declined thereafter. We subjected 86 isolates for further antibiotic susceptibility testing using E-test, screened for MBL and carbapenemase production, and performed PCR for blaOXA genes. Statistical analyses included correlation of resistance genes with susceptibility. Sixty-one isolates were non-susceptible to carbapenems (MIC >2 μg/mL). Phenotypic screening showed carbapenemase production in 50 isolates, but none was positive for MBL. Among carbapenem non-susceptible isolates, the CHDL (group D carbapenemase) encoding genes blaOXA-23 (52%) and blaOXA-40 (28%) were the most frequent genes. In conclusion, carbapenem resistance rates in A. baumannii peaked in 2011 and have since declined in our region. Carbapenem resistance among A. baumannii was primarily associated with production of acquired CHDLs including OXA-23 and OXA-40.

1205. Emergence of Carbapenemase Producing Enterobacteriaceae in South Central Ontario, Canada

BackgroundThe spread of CPE is an increasing global threat to patient safety. We describe the introduction and evolution of CPE in south-central Ontario, Canada.MethodsThe Toronto Invasive Bacterial Diseases Network has performed population based surveillance for CPE in metropolitan Toronto and Peel region from first identified isolates in 2007. All laboratories test/refer all carbapenem non-susceptible Enterobacterial isolates for PCR testing for carbapenemases. Demographic and medical data and travel history are collected from chart review and patient/physician interview.ResultsSince 2007, 659 patients have been identified as colonized/infected with CPE; 362, 57%) have at least one clinical isolate. Annual incidence has increased from 0 in 2006 to 1.3 per 100,000 in 2016/17 (Figure 1). First bacteremia occurred in 2010, the incidence in 2017 was 0.14 per 100,000 population. 388 (59%) patients were male, median age was 70 years (range 3 months–100 years). Most common genes among first isolates were NDM (306, 46%), OX48 (149, 23%), KPC (122, 19%). Most common species were K. pneumoniae (268, 41%) and E. coli (259, 39%). Over time, second species/same gene were identified in 113 (16%) patients. In addition, 34/xxx patients with isolates with NDM and/or OXA-48 subsequently had a second isolate with a different gene/gene combination. Of 518 patients whose travel and hospitalization history are available, patients with VIM were less likely than other patients to have a foreign hospitalization or travel history (9/28 vs. 341/490, P < 0.0001). Patients with KPC were more likely to have a hospitalization history outside Canada and the Indian subcontinent (25/70, 36%), in Canada (47/164,29%) than to have no hospitalization in the last year (13/93, 14%), or a history of hospitalization in the Indian subcontinent (2/191, 1%) (P < 0.001). The number of incident patients with different hospitalization and travel history over time is shown in Figure 2.ConclusionCPE is increasingly recognized in southern Ontario, both in patients with a history of exposure in healthcare in other countries, and to healthcare in Canada. Intensification of control programs is urgently needed.Figure 1.Incidence of clinical isolates of CPE over time.Figure 2.Number of incident CPE cases with different hospitalization (H) and travel (T) history over time.Disclosures S. Poutanen, MERCK: Scientific Advisor, Speaker honorarium. COPAN: Speaker(but not part of a bureau), Travel reimbursement. Accelerate Diagnostics: Investigator, Research support. Bio-Rad: Investigator, Research support. bioMérieux: Investigator, Research support.

Detection of Metallo-Beta-Lactamase-Encoding Genes Among Clinical Isolates of Pseudomonas aeruginosa in Qom Province

Background: Carbapenem-resistant Pseudomonas aeruginosa has emerged as a serious problem in many hospitals and intensive care units. The purpose of this study was to determine the antibiotic susceptibility profile and the distribution of metallo-beta-lactamase genes among P. aeruginosa isolates from Qom province of Iran. Methods: In this study, 200 P. aeruginosa isolates were collected from several clinical samples in hospitals affiliated to Qom University of Medical Sciences, Qom province, Iran. The antibiotic susceptibility of the isolates was tested by the Kirby-Bauer disc diffusion test and the distribution of MBL genes among carbapenem-resistant isolates was determined by polymerase chain reaction (PCR) method. Results: Among carbapenem non-susceptible isolates of P. aeruginosa, 38% (76 isolates) were multidrug resistant, 26% (52 isolates) were pan-drug-resistant and 5% (10 isolates) were extensive drug resistant. 52% of the isolates were resistant to carbapenems. Among carbapenem non-susceptible isolates of P. aeruginosa, 40 isolates (38.4%) exhibited MBL production. Of 40 MBL-producing isolates, 38 isolates (36.5%) contained the blaIMP gene and two (1.9%) isolates contained the blaVIM gene. Conclusions: Outbreaks of MBL-producing P. aeruginosa isolates will be a serious problem in hospitals in the future and rapid identification of these isolates is necessary to control further dissemination of MBL resistance genes. This is the first report of the rates of MDR, XDR, PDR, and MBL-producing P. aeruginosa isolated from hospitals affiliated to Qom University of Medical Sciences in Qom province of Iran.

Carbapenem-Nonsusceptible Gram-Negative Pathogens in ICU and Non-ICU Settings in US Hospitals in 2017: A Multicenter Study.

BackgroundInfections caused by Gram-negative pathogens resistant to carbapenems have limited treatment options and are associated with increased morbidity and mortality. We evaluated the rates, infection sources, and pathogen types associated with carbapenem-nonsusceptible (Carb-NS) Gram-negative isolates in intensive care unit (ICU) and non-ICU settings in a large US hospital database.MethodsWe conducted a retrospective cross-sectional analysis of carbapenem susceptibility of all nonduplicate isolates of Gram-negative pathogens collected from January 1, 2017, to December 31, 2017, at 358 US hospitals in the BD Insights Research Database. Carb-NS isolates included all pathogens reported at the institutional level as intermediate or resistant.ResultsOf 312 075 nonduplicate Gram-negative isolates, 10 698 (3.4%) were Carb-NS. Respiratory samples were the most frequent source of Carb-NS isolates (35.2%); skin/wound accounted for 23.6%. Pseudomonas aeruginosa was the most common Carb-NS pathogen (58.5% of isolates), and about 30% were Enterobacteriaceae. The highest rates of Carb-NS were found in Acinetobacter spp. (35.6%) and P. aeruginosa (14.6%). The rate of Carb-NS was significantly higher in ICU (5.4%) vs non-ICU settings (2.7%; P < .0001 in univariate analysis). This difference remained significant in multivariable analysis after adjusting for infection and hospital characteristics (odds ratio, 1.35; 95% confidence interval, 1.17–1.56; P < .0001).ConclusionsInfections caused by Carb-NS isolates pose a significant clinical problem across different sources of infection, species of pathogen, and hospital settings. Widespread infection prevention and antimicrobial stewardship initiatives, in combination with new treatment options, may be required to reduce the burden of carbapenem resistance in health care settings.

Laboratory based antimicrobial resistance surveillance for Pseudomonas aeruginosa blood isolates from South Africa.

Antimicrobial resistant bacterial infections are widespread globally and increases in antimicrobial resistance presents a major threat to public health. Pseudomonas aeruginosa is an opportunistic healthcare-associated pathogen with high rates of morbidity and mortality and an extensive range of resistance mechanisms. This study describes the antibiotic susceptibility profiles of P. aeruginosa isolates from patients with bacteraemia submitted by sentinel laboratories in South Africa from 2014 to 2015. Organism identification and antimicrobial susceptibility testing were done using automated systems. Molecular methods were used to detect common resistance genes and mechanisms. Overall the susceptibility was high for all antibiotics tested with a decrease over the two-year period. There was no change in the MIC50 and MIC90 breakpoints for all antibiotics from 2014 to 2015. The MIC50 was within the susceptible breakpoint range for most antibiotics and the MIC90 was within the susceptible breakpoint range for colistin only. Phenotypically carbapenem non-susceptible isolates harboured the following plasmid-mediated genes: blaVIM (n = 81, 12%) and blaGES (n = 6, 0.9%); blaNDM (n = 4, 0.6%) and blaOXA-48 and variants (n = 3, 0.45%). Porin deletions were observed in one meropenem non-susceptible isolate only, and multi-drug resistance efflux pumps were expressed in the majority of the non-susceptible isolates investigated. BlaVEB-1, blaIMP and blaKPC were not detected. The prevalence of resistance to commonly used antibacterial agents was low for P. aeruginosa isolates and similarly, tested resistance mechanisms were detected in a relatively small proportion of isolates. Findings in this study represent baseline information for understanding antimicrobial susceptibility patterns in P. aeruginosa isolates from blood. Our surveillance report may assist in contributing to hospital treatment guidelines.

Carbapenem non-susceptibility of Klebsiella pneumoniae isolates in hospitals from 2011 to 2016, data from the German Antimicrobial Resistance Surveillance (ARS)

BackgroundCarbapenem resistance in Klebsiella pneumoniae is of significant public health concern and recently spread across several countries. We investigated the extent of carbapenem non-susceptibility in K. pneumoniae isolates in Germany.MethodsWe analysed 2011–2016 data from the German Antimicrobial Resistance Surveillance (ARS) System, which contains routine data of antimicrobial susceptibility testing from voluntarily participating German laboratories. Klebsiella pneumoniae isolates tested resistant or intermediate against an antibiotic were classified as non-susceptible.ResultsWe included 154,734 isolates from 655 hospitals in the analysis. Carbapenem non-susceptibility in K. pneumoniae isolates was low in Germany 0.63% (95% CI 0.51–0.76%). However, in continuously participating hospitals the number of K. pneumoniae isolates almost doubled and we found evidence for a slowly increasing trend for non-susceptibility (OR = 1.20 per year, 95% CI 1.09–1.33, p < 0.001). Carbapenem non-susceptibility was highest among isolates from patients aged 20–39 in men but not in women. Moreover, carbapenem non-susceptibility was more frequently reported for isolates from tertiary care, specialist care, and prevention and rehabilitation care hospitals as well as from intensive care units. Co-resistance of carbapenem non-susceptible isolates against antibiotics such as tigecycline, gentamicin, and co-trimoxazole was common. Co-resistance against colistin was 13.3% (95% CI 9.8–17.9%) in carbapenem non-susceptible isolates.ConclusionCarbapenem non-susceptibility in K. pneumoniae isolates in Germany is still low. However, it is slowly increasing and in the light of the strong increase of K. pneumoniae isolates over the last year this poses a significant challenge to public health. Continued surveillance to closely monitor trends as well as infection control and antibiotic stewardship activities are necessary to preserve treatment options.

Long-Term, Low-Frequency Cluster of a German-Imipenemase-1-Producing Enterobacter hormaechei ssp. steigerwaltii ST89 in a Tertiary Care Hospital in Germany.

Enterobacter cloacae complex is a common cause of hospital outbreaks. A retrospective and prospective molecular analysis of carbapenem-resistant clinical isolates in a tertiary care center demonstrated an outbreak of a German-imipenemase-1 (GIM-1) metallo-beta-lactamase-producing Enterobacter hormaechei ssp. steigerwaltii affecting 23 patients between 2009 and 2016. Thirty-three isolates were sequence type 89 by conventional multilocus sequence typing (MLST) and displayed a maximum difference of 49 out of 3,643 targets in the ad-hoc core-genome MLST (cgMLST) scheme (SeqSphere+ software; Ridom, Münster, Germany). The relatedness of all isolates was confirmed by further maximum-likelihood phylogeny. One clonal complex of highly related isolates (≤15 allele difference in cgMLST) contained 17 patients, but epidemiological data only suggested five transmission events. The blaGIM-1-gene was embedded in a class-1-integron (In770) and the Tn21-subgroup transposon Tn6216 (KC511628) on a 25-kb plasmid. Environmental screening detected one colonized sink trap in a service room. The outbreak was self-limited as no further blaGIM-1-positive E. hormaechei has been isolated since 2016. Routine molecular screening of carbapenem-nonsusceptible gram-negative isolates detected a long-term, low-frequency outbreak of a GIM-1-producing E. hormaechei ssp. steigerwaltii clone. This highlights the necessity of molecular surveillance.

Identification of VIM-2 metallo-β-lactamase-producing Pseudomonas aeruginosa isolated from dogs with pyoderma and otitis in Korea.

Pseudomonas aeruginosa is a challenging pathogen cultured from cases of acute and chronic canine otitis and sometimes in cases of deep pyoderma. The spread of antimicrobial resistance, especially carbapenem resistance, is a serious therapeutic challenge worldwide. To investigate the identification and characterization of resistant P. aeruginosa clinical canine isolates. Clinical isolates (n = 80) were collected from dogs with pyoderma (n = 18) and otitis (n = 62) in Korea. Antimicrobial susceptibility was determined using agar dilution and using Clinical and Laboratory Standards Institute guidelines for recording susceptibility for human Pseudomonas isolates; genetic relatedness of isolates was investigated by multilocus sequence typing (MLST) and SpeI macrorestriction analysis. The class 1 integrons were amplified and sequenced using primer walking. Most isolates were susceptible to colistin (97.5%), polymyxin B (96.3%), ciprofloxacin (81.3%) and meropenem (80.0%); whereas resistance to aztreonam (80%), piperacillin (52.5%), piperacillin/tazobactam (41.3%) and cefepime (37.5%) was high; 12 carbapenem-nonsusceptible isolates (15%) were detected. MLST revealed 45 different sequence types (STs) and macrorestriction analysis detected 55 distinct pulsotypes (PTs), which were divided into 25 clonal groups. Among carbapenem-nonsusceptible isolates, 10 (83.3%) were VIM-2-producing strains. Nine VIM-2-producing isolates were identified as ST1047 and harboured the same 2.8 kb class 1 integron. One remaining isolate was ST1203 with 2.1 kb class 1 integron. This study demonstrated the diversity of the phenotype and genotype of clinical P. aeruginosa isolates from dogs with pyoderma and otitis. The identification of VIM-2-producing P. aeruginosa in dogs is alarming and warrants further surveillance.

Characterization of Isolates Associated with Emergence of OXA-48-Producing Klebsiella pneumoniae in Croatia.

Here, we report a retrospective study conducted to elucidate emergence, epidemiology, and molecular mechanisms of resistance underlying the early spread of OXA-48 carbapenemase-producing Enterobacteriaceae in Croatia. Retrospective screening for OXA-48 producers was performed on a collection of 296 nonrepetitive, carbapenem-nonsusceptible enterobacterial isolates collected from January 2011 to December 2012 from 40 participating centers in Croatia. Antimicrobial susceptibility profiles and production of carbapenemases were assessed phenotypically. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing were used for epidemiological analysis. Resistance genes were characterized by polymerase chain reaction (PCR) and sequencing. Plasmid localization of blaOXA-48 in isolates and transconjugants was investigated by S1-PFGE and Southern hybridization. PCR mapping was used for identification of genetic platform surrounding blaOXA-48. Out of 296 carbapenem-nonsusceptible isolates, blaOXA-48 gene was detected in 12 Klebsiella pneumoniae isolates. All OXA-48-producing isolates showed varying resistance to carbapenems and 11 were multidrug resistant. All coproduced additional beta-lactamases, including CTX-M-15, which was detected in eight isolates. Isolates were delineated in five clonal types by PFGE corresponding to five sequence types (STs) assigned ST15, ST16, ST37, ST528, and ST1418. All OXA-48 isolates conjugated successfully and other resistance determinants were not cotransferred. blaOXA-48 was carried on a ∼60 kb IncL/M plasmid and was detected within Tn1999.2 composite transposon. OXA-48, a class D carbapenemase, is emerging as a potentially significant contributor among carbapenem-resistant Enterobacteriaceae in Croatia, alongside class A and B carbapenemases. Polyclonal genetic background of K. pneumoniae isolates carrying ∼60 kb incL/M plasmid indicates that dissemination of the blaOXA48 gene is not driven exclusively by the spread of a single clone.

First report of OXA-143-lactamase producing Acinetobacter baumannii in Qom, Iran.

Objective(s):Antibiotic resistance in Acinetobacter baumannii and outbreaks caused by this organism have been reported from several areas of the world. The present study aimed at determining the antibiotic susceptibility profiles and the distribution of OXA-type beta-lactamases among Iranian Acinetobacter baumannii isolates from Qom of Iran.Materials and Methods:For this study, 108 non-duplicate A. baumannii isolates were obtained from clinical specimens in four teaching hospitals in Qom in the central of Iran. The antimicrobial susceptibility of isolates was tested by standard disk diffusion and prevalence of bla OXA genes was investigated by PCR method.Results:Among 97 carbapenem non-susceptible isolates of A. baumannii, 90.72% (88 isolates) isolates showed extensive drug resistance to multiple antibiotics. Among carbapenem resistant isolates, 100% carried blaOXA-51-like, 82.47% carried blaOXA-23-like, 55.67% carried blaOXA-58-like, 22.68% carried blaOXA-40-like and 14.43% had blaOXA-143-like resistance genes.Conclusion:This study demonstrated high genetic diversity of OXA genes among isolates of A. baumannii in Qom, Iran.

In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against a Recent Collection of Clinically Relevant Gram-Negative Bacilli from North America and Europe, Including Carbapenem-Nonsusceptible Isolates (SIDERO-WT-2014 Study).

ABSTRACTCefiderocol (formerly S-649266) is an investigational siderophore cephalosporin. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) was prepared according to the Clinical and Laboratory Standards Institute (CLSI) protocol and used to perform broth microdilution testing of cefiderocol against a 2014-2015 collection of clinical isolates of Gram-negative bacilli from North America (n = 4,239) and Europe (n = 4,966). The concentrations of cefiderocol inhibiting 90% of isolates tested (MIC90s) were 0.5 μg/ml (North America; n = 3,007) and 1 μg/ml (Europe; n = 3,080) for all isolates of Enterobacteriaceae; 1 μg/ml (North America; n = 30) and 4 μg/ml (Europe; n = 139) for meropenem-nonsusceptible (MIC ≥ 2 μg/ml) isolates of Enterobacteriaceae; 0.5 μg/ml for both North American (n = 765) and European (n = 765) isolates of Pseudomonas aeruginosa; 0.5 μg/ml (North America; n = 151) and 1 μg/ml (Europe; n = 202) for meropenem-nonsusceptible (MIC ≥ 4 μg/ml) isolates of P. aeruginosa; 1 μg/ml for both North American (n = 309) and European (n = 839) isolates of all Acinetobacter baumannii strains as well as for both North American (n = 173) and European (n = 595) isolates of meropenem-nonsusceptible A. baumannii; and 0.5μg/ml (North America; n = 152) and 0.25 μg/ml (Europe; n = 276) for isolates of Stenotrophomonas maltophilia. MICs of cefiderocol were ≤4 μg/ml for 99.9% (6,078/6,087) of all Enterobacteriaceae, 97.0% (164/169) of meropenem-nonsusceptible Enterobacteriaceae, 99.9% (1,529/1,530) of all P. aeruginosa isolates, 100% (353/353) of meropenem-nonsusceptible P. aeruginosa isolates, 97.6% (1,120/1,148) of all A. baumannii isolates, 96.9% (744/768) of meropenem-nonsusceptible A. baumannii isolates, 100% of isolates of S. maltophilia (428/428) and 93.8% of isolates of Burkholderia cepecia (11/12). We conclude that cefiderocol demonstrated potent in vitro activity against a recent collection of clinical isolates of commonly encountered Gram-negative bacilli, including carbapenem-nonsusceptible isolates.

In vitro susceptibility and resistance phenotypes in contemporary Enterobacter isolates in a university hospital in Crete, Greece.

To study the evolution in the susceptibility of Enterobacter spp. in Crete, Greece from 2010 to 2015. Non-duplicate isolates were studied using automated systems. Phenotypic confirmatory tests were applied. A total of 939 Enterobacter isolates were included. Colistin was the most active antibiotic (97.9%) followed by imipenem (96.1%), gentamicin (95.7%), tigecycline (91.8%), cefepime (89.4%), chloramphenicol (85.8%), fosfomycin (85.5%), trimethoprim/sulfamethoxazole (83.3%) and piperacillin/tazobactam (73.3%). Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility was observed among multidrug-resistant strains and carbapenem-nonsusceptible isolates. AmpC was the most common resistant mechanism (21%); carbapenemases (3.7%) and aminoglycoside-modifying enzymes (6.5%) were also detected. A significant proportion of Enterobacter spp. was resistant to several antibiotics, most notably β-lactams.

Heterogeneity of Carbapenem Resistance Mechanisms Among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study.

Carbapenem-resistant Gram-negative pathogens have progressively disseminated to different countries worldwide, presenting a serious public health concern. The aims of this study were to determine the prevalence of carbapenem resistance in Gram-negative bacteria in Lebanon, to elucidate molecular mechanisms, and to identify genetic relatedness of incriminated strains. Carbapenem nonsusceptible Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas were collected from 11 Lebanese hospitals in 2012. Antimicrobial susceptibility was assessed with phenotypic tests, genes encoding carbapenemases were screened via PCR-sequencing, and genetic relatedness was examined by PGFE and ERIC-PCR. A total of 398 nonrepetitive carbapenem nonsusceptible isolates were studied, of which 44 were Enterobacteriaceae, 142 were A. baumannii, and 212 were Pseudomonas. Among Enterobacteriaceae, 70.4% carried blaOXA-48-like gene on IncL/M-type plasmids, while acquired AmpC cephalosporinases, extended-spectrum-β-lactamases, and efflux-pump were additional contributors to carbapenem resistance. Among A. baumannii, 90% produced OXA-23 and GES-11 and carried insertion sequence ISAba1 upstream and adjacent to blaOXA-23 and blaAcinetobacter-derived cephalosporinases. Among Pseudomonas, 16% harbored VIM-2, 4.2% IMP-2, and 1.4% IMP-1 metallo-β-lactamases. Fingerprint analysis indicated that the spread of OXA-48-like carbapenemases was mostly mediated by horizontal transfer, while OXA-23 and GES-11 diffusion in A. baumannii and VIM-2 diffusion in P. aeruginosa were primarily due to clonal dissemination. This study is the first nationwide investigation of carbapenem resistance in Lebanon, showing low level of resistance in Enterobacteriaceae, and higher levels in A. baumannii and Pseudomonas. With current changes in the region, continuous surveillance of carbapenem resistance is crucial.

Carbapenem Nonsusceptibility with Modified OprD in Clinical Isolates of Pseudomonas aeruginosa from India

This study was undertaken to investigate OprD porin-mediated carbapenem nonsusceptibility in clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital of Northeast India. A total of 267 nonduplicate, consecutive clinical isolates of P. aeruginosa were obtained. Mutation and expression levels of OprD gene were determined in carbapenem-nonsusceptible carbapenemase-nonproducing isolates. Among 19 carbapenem-nonsusceptible carbapenemase-nonproducing isolates, 11 of them demonstrated variable band pattern while performing denaturing gradient gel electrophoresis with amplified products of OprD gene. Sequencing of variable band products revealed three mutation patterns in three isolates. Relevant decrease in expression of OprD gene could also be observed in them. All the three isolates exhibited a higher minimum inhibitory concentration for imipenem (64–128 μg/mL) compared to meropenem (16–64 μg/mL). Inactivating mutation and decreased expression of OprD contribute mainly to imipenem resistance as well as to meropenem.

Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study

Gaps in the diagnostic capacity and heterogeneity of national surveillance and reporting standards in Europe make it difficult to contain carbapenemase-producing Enterobacteriaceae. We report the development of a consistent sampling framework and the results of the first structured survey on the occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in European hospitals. National expert laboratories recruited hospitals with diagnostic capacities, who collected the first ten carbapenem non-susceptible clinical isolates of K pneumoniae or E coli and ten susceptible same-species comparator isolates and pertinent patient and hospital information. Isolates and data were relayed back to national expert laboratories, which made laboratory-substantiated information available for central analysis. Between Nov 1, 2013, and April 30, 2014, 455 sentinel hospitals in 36 countries submitted 2703 clinical isolates (2301 [85%] K pneumoniae and 402 (15%) E coli). 850 (37%) of 2301 K pneumoniae samples and 77 (19%) of 402 E coli samples were carbapenemase (KPC, NDM, OXA-48-like, or VIM) producers. The ratio of K pneumoniae to E coli was 11:1. 1·3 patients per 10 000 hospital admissions had positive clinical specimens. Prevalence differed greatly, with the highest rates in Mediterranean and Balkan countries. Carbapenemase-producing K pneumoniae isolates showed high resistance to last-line antibiotics. This initiative shows an encouraging commitment by all participants, and suggests that challenges in the establishment of a continent-wide enhanced sentinel surveillance for carbapenemase-producing Enterobacteriaeceae can be overcome. Strengthening infection control efforts in hospitals is crucial for controlling spread through local and national health care networks. European Centre for Disease Prevention and Control.

Molecular Epidemiology and Outcomes of Carbapenem Non-Susceptible Clinical Isolates in Detroit

Molecular Epidemiology and Outcomes of Carbapenem Non-Susceptible Clinical Isolates in Detroit

Increasing incidence of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in Belgian hospitals.

Carbapenemase-producing Enterobacteriaceae are increasingly reported worldwide. The aim of the study was to determine the incidence and molecular epidemiology of carbapenemase-producing (CP) Escherichia coli and Klebsiella pneumoniae (CP-E/K) in Belgium. Eleven hospital-based laboratories collected carbapenem non-susceptible (CNS) isolates of E. coli and K. pneumoniae detected in clinical specimens from January 2013 to December 2014. All CNS strains were tested for carbapenemase production and typed by multilocus sequence typing (MLST) for a 6-month period as part of the European Survey on Carbapenemase-Producing Enterobacteriaceae in Europe (EuSCAPE) structured survey. In addition, an equal number of carbapenem-susceptible isolates collected were preserved as a control group for risk factor analysis. The overall incidence rate of CP-E/K isolates in hospitals increased from 0.124 in 2013 to 0.223 per 1000 admissions in 2014. From November 2013 to April 2014, 30 CP K. pneumoniae [OXA-48 (n = 16), KPC (n = 13), OXA-427 (n = 1)] and five CP E. coli [OXA-48 (n = 3), NDM (n = 1), OXA-427 (n = 1)] isolates were detected in ten hospitals. The 16 OXA-48-producing K. pneumoniae strains were distributed into eight sequence types (STs), while the 13 KPC-producing K. pneumoniae clustered into three STs dominated by ST512 (n = 7) and ST101 (n = 5). Compared to controls, we observed among CP-E/K carriers significantly higher proportion of males, respiratory origins, previous hospitalization, nosocomial setting, and a significantly lower proportion of bloodstream infections. Our study confirms the rapid spread of CP-E/K in Belgian hospitals and the urgent need for a well-structured and coordinated national surveillance plan in order to limit their dissemination.

Prevalence of Class 1, 2 and 3 Integrons and Carbapenem-Resistance in Gram-Negative Bacteria

Background: Resistance to various antimicrobial agents in gram-negative bacteria has become an important health threat with some acquired through integrons. Objectives: The present study aims to evaluate the resistance profiles, and the prevalance of integrases in gram-negative isolates. Methodology: We examined 70 gram negative isolates comprising 35 carbapenem-susceptible and 35 carbapenem-nonsusceptible isolates for antimicrobial resistance patterns against 13 antibiotics and the screening for integrases by polymerase chain reaction. Results: Isolates comprised 41 Enterobacteriaceae, 17 Pseudomonas aeruginosa, and 12 Acinetobacter baumannii. Pseudomonas aeruginosa was the most common detected among our isolates, followed by Escherichia coli and Acinetobacter baumanniii. Carbapenem-nonsusceptible gram-negative isolates showed significant higher rates of resistance to all tested antibiotics except for aztreonam. Class 1 were found among 12 and 29 isolates, while class 2 were detected in two and 9 isolates of carbapenem-susceptible and non-susceptible isolates, respectively with significant differences between both groups. None of the isolates expressed class 3 integrons. Class 1 integrons were mostly detected among Pseudomonas aeruginosa, Acinetobacter baumanniii, and Escherichia coli in both groups. Conclusion: Integrases were common among our gram-negative isolates. Their high prevalence denotes that the hospital environment may favor the formation of resistant gene cassettes that necessitate the application of effective measures to fight them.

Active surveillance scheme in three Romanian hospitals reveals a high prevalence and variety of carbapenamase-producing Gram-negative bacteria: a pilot study, December 2014 to May 2015.

We report the findings of an active surveillance scheme for detection of asymptomatic carriers with carbapenemase-producing Gram-negative bacteria (CP-GNB) in Romanian hospitals. During a pilot study from December 2014 to May 2015, faecal cultures were screened in three hospitals (two large, one medium-size) for patients newly admitted to selected wards or inpatients transferred from other wards to an intensive-care unit. The study revealed a high prevalence of CP-GNB detected in 22/27 and 28/38 of the carbapenem non-susceptible isolates from Hospitals 1 and 3, respectively. CP-GNB identified through faecal screening included NDM-1-producing Serratia marcescens and Klebsiella pneumoniae, OXA-48-producing K. pneumoniae and OXA-23-producing Acinetobacter baumannii. The distribution of the CP-GNB varied between the hospitals, with NDM-1-producing S. marcescens and K. pneumoniae being prevalent in the north-central part of the country and OXA-23/24-producing A. baumannii, OXA-48-producing K.pneumoniae, Morganella morganii and VIM-2-producing Escherichia coli/Pseudomonas aeruginosa detected in the north-east of the country. Conjugation studies showed that carbapenem resistance was transferable and PCR-based replicon typing identified blaNDM-1 on IncFIIs in S. marcescens and K. pneumoniae from Hospital 1 and blaOXA-48 on IncL plasmids in all Klebsiella spp. isolates from Hospitals 1 and 3. Our findings underline the importance of active surveillance for detection of CP-GNB asymptomatic faecal carriers and suggest a likely endemic spread of CP-GNB in Romania.