Carbapenem-nonsusceptible Strains Research Articles

Incidence of carbapenem-resistant Escherichia coli ST2437 of clinical origin harbouring blaOXA-144 gene: a report from India.

Carbapenem-resistant Escherichia coli has been categorized as a pathogen of critical priority by the World Health Organization as it is highly infectious with high mortality and morbidity rates and widespread transmission potential. Carbapenem resistance is primarily mediated by carbapenemase-encoding genes and, additionally, through intrinsic factors. In India, over the years, carbapenemase-encoding genes have been reported from diverse clinically significant pathogens. The present study identifies E. coli of clinical origin that harbours blaOXA-144. The study isolate was obtained from a tertiary referral hospital in northeast India. Carbapenemase production was investigated through culture on chromogenic agar and Rapidec Carba NP test as per manufacturer's instructions. Susceptibility of the isolate was performed by the Kirby-Bauer disc diffusion method and agar dilution method following CLSI guidelines. PCR targeting carbapenemase-encoding genes was performed, followed by transformation and conjugation experiments. Whole-genome sequencing of the isolate was done through the Illumina sequencing platform and the data were analysed using the Centre for Genomic Epidemiology database. BJD_EC180 is 6 919 180 bp in length and consists of six rRNA operons, 111 tRNA, and 6849 predicted protein-coding sequences. BJD_EC180 belonged to ST2437 and harboured the carbapenemase-encoding gene blaOXA-144 with ISAba1 upstream, along with multiple antibiotic resistance genes conferring clinical resistance towards beta-lactams, aminoglycosides, amphenicols, sulphonamides, tetracyclines, trimethoprim, and rifampin. Carbapenem-resistant E. coli harbouring blaOXA-144 associated with insertion sequence pose a serious health threat as their mobilization into carbapenem non-susceptible strains that will contribute to the resistance burden and therefore, needs urgent monitoring.

Emergence of carbapenem-resistant enterobacterales co-harboring blaOXA−78 and blaOXA−58 from India

BackgroundCarbapenem-Resistant Enterobacterales (CRE) has been categorized as pathogens of critical priority by World Health organization (WHO) as they pose significant threat to global public health. Carbapenemase production considered as the principal resistance mechanism against carbapenems and with the recent surge and expansion of carbapenemases and its variants among clinically significant bacteria in India, the present study reports expansion blaOXA−78 and blaOXA−58 of in CRE of clinical origin.MethodsBacterial isolates were collected from a tertiary referral hospital and identified through VITEK® 2 Compact automated System (Biomerieux, France). Rapidec® Carba NP (Biomerieux, France) was used to investigate carbapenemase production followed by antibiotic susceptibility testing through Kirby-Bauer Disc Diffusion method and agar dilution method. Class D carbapenemase genes were targeted through PCR assay followed by investigation of horizontal transmission of blaOXA−58 and blaOXA−78. Whole genome sequencing was carried out using Illumina platform to investigate the genetic context of blaOXA−58 and blaOXA−78 genes and further characterization of the CRE isolates.ResultsThe carbapenem-resistant Escherichia coli (BJD_EC456) and Serratia marcescens (BJD_SM81) received during the study from the tertiary referral hospital were isolated from sputum and blood samples respectively. PCR assay followed by whole genome sequencing revealed that the isolates co-harbor blaOXA−58 and blaOXA−78, a variant of blaOXA−51. Horizontal transfer of blaOXA−58 and blaOXA−78 genes were unsuccessful as these genes were located on the chromosome of the study isolates. Transposon Tn6080 was linked to blaOXA−78 in the upstream region while the insertion sequences ISAba26 and ISCfr1 were identified in the upstream and downstream region of blaOXA−58 gene respectively. In addition, both the isolates were co-harboring multiple antibiotic resistance genes conferring clinical resistance towards beta-lactams, aminoglycosides, fluroquinolones, sulphonamides, tetracyclines. BJD_EC180 belonged to ST2437 while BJD_SM81 was of an unknown sequence type. The nucleotide sequences of blaOXA−78 (OQ533021) and blaOXA−58 (OQ533022) have been deposited in GenBank.ConclusionsThe study provides a local epidemiological information regarding carbapenem resistance aided by transposon and insertion sequences associated blaOXA−78 and blaOXA−58 genes associated and warrants continuous monitoring to prevent their further dissemination into carbapenem non-susceptible strains thereby contributing to carbapenem resistance burden which is currently a global concern.

Utilization of an immunochromatographic lateral flow assay for rapid detection of carbapenemase production in gram negative bacilli.

Rapid detection of carbapenemase production in gram negative bacilli has important treatment considerations. We evaluated a lateral flow assay (LFA) for carbapenemase production compared with molecular detection of 5 (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48) carbapenemase genes. A total of 218 carbapenem nonsusceptible strains, including species of Enterobacterales, Pseudomonas aeruginosa isolated from clinical cultures were tested using the Cepheid Xpert Carba-R assay and the NG Biotech Carba-5 lateral flow immunoassay. Overall agreement with LFA was 98.2% with accuracy for each target >99% compared with polymerase chain reaction. Results were available within 15 minutes compared with 1 hour for molecular detection. The use of accurate, rapid diagnostics compliments antimicrobial stewardship programs.

Various arrangements of mobile genetic elements among CC147 subpopulations of Klebsiella pneumoniae harboring blaNDM-1: a comparative genomic analysis of carbapenem resistant strains

BackgroundCertain clonal complexes (CCs) of Klebsiella pneumoniae such as CC147 (ST147 and ST392) are major drivers of blaNDM dissemination across the world. ST147 has repeatedly reported from our geographical region, but its population dynamics and evolutionary trajectories need to be further studied.MethodsComparative genomic analysis of 51 carbapenem-nonsusceptible strains as well as three hypervirulent K. pneumoniae (hvKp) recovered during 16-months of surveillance was performed using various bioinformatics tools. We investigated the genetic proximity of our ST147 strains with publicly available corresponding genomes deposited globally and from neighbor countries in our geographic region.ResultsWhile IncL/M plasmid harboring blaOXA-48 was distributed among divergent clones, blaNDM-1 was circulated by twenty of the 25 CC147 dominant clone and were mostly recovered from the ICU. The NDM-1 core structure was bracketed by a single isoform of mobile genetic elements (MGEs) [ΔISKpn26-NDM-TnAs3-ΔIS3000-Tn5403] and was located on Col440I plasmid in 68.7% of ST392. However, various arrangements of MGEs including MITESen1/MITESen1 composite transposon or combination of MITESen1/ISSen4/IS903B/IS5/ISEhe3 on IncFIb (pB171) were identified in ST147. It seems that ST392 circulated blaNDM-1 in 2018 before being gradually replaced by ST147 from the middle to the end of sample collection in 2019. ST147 strains possessed the highest number of resistance markers and showed high genetic similarity with four public genomes that harbored blaNDM-1 on the same replicon type. Mainly, there was a convergence between clusters and isolated neighboring countries in the minimum-spanning tree. A conserved arrangement of resistance markers/MGEs was linked to methyltransferase armA which was embedded in class 1 integron in 8 isolates of ST147/ST48 high-risk clones.ConclusionOur findings highlight the dynamic nature of blaNDM-1 transmission among K. pneumoniae in Iran that occurs both clonally and horizontally via various combinations of MGEs. This is the first analysis of Iranian ST147/NDM + clone in the global context.

624. Probability of Target Attainment of Ceftolozane/Tazobactam Among Adult Patients with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Secondary to Pseudomonas aeruginosa in Latin America

Abstract Background Pseudomonas aeruginosa (Pa) is a common cause of nosocomial pneumonia; resistance among traditionally used empiric agents is observed frequently. To improve patient outcomes, a heightened focus has been placed on evaluating the adequacy of recommended dosing regimens, particularly of beta-lactams. The Phase 3 study ASPECT-NP demonstrated the efficacy and safety of 3 g of ceftolozane/tazobactam (C/T) infused every 8 h for 8 to 14 days for treatment of adults with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia (HAP/VAP). We assessed the Probability of Target Attainment (PTA) of the C/T 3g dosage regimen in patients with HAP/VAP due to Pa, with an additional focus on carbapenem-resistant Pa, from Latin America. Methods Non duplicate Pa isolates from a respiratory source were collected as part of the SMART surveillance program from 36 sites in 10 Latin American countries during 2017-2020. MICs were determined by broth microdilution and interpreted by CLSI criteria. C and T concentration-time profiles were simulated in plasma and ELF following administration of the approved 3g (2g/1g) C/T dose (or equivalent dose adjusted based on renal function) administered by 1-hour infusion every 8 hours. PTA in plasma and ELF was calculated using the PK/PD target of 30% fT > MIC for C. T does not contribute to the antipseudomonal activity of C and therefore was not considered. Results A total of 2,757 P. aeruginosa were collected, of which 1208 (43.8%) were carbapenem nonsusceptible. C/T susceptiblity was 87.7% against all Pa and 73.4% among carbapenem nonsusceptible strains. At C/T doses of 2g/1g (CrCL > 50mL/min); 1g/0.5g (30mL/min≤ CrCL≤ 50mL/min), and 500mg/250mg (15mL/min≤ CrCL≤29mL/min), steady-state ceftolozane plasma and ELF PTA was 100% and > 99%, respectively, for isolates with an MIC at the Pa susceptiblity breakpoint of 4 µg/mL. Ceftolozane plasma and ELF PTA remained above 90% up to an MIC of 16 µg/mL and 8 µg/mL, respectively. Conclusion The regulatory approved pneumonia dosage regimen of C/T 3g (administered over 1 hour) every 8 hours (or equivalent dose adjusted based on renal function) resulted in high plasma and ELF PTAs sufficient to cover the vast majority of circulating P. aeruginosa present in Latin America, including carbapenem resistant strains. Disclosures Aline Okuma, PharmD, MSD Brazil: Employee Thales Polis, MD, MSD Brazil: Employee Jacqueline Pavia, MD, MSD COLOMBIA: EMPLOYEE Gustavo Mizuno, PharmD, MSD Brazil: Employee Jacqueline Ferrari, MD, MSD Brazil: Employee Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds.

The susceptibility pattern and distribution of blaOXA-23 genes of clinical isolate Acinetobacter baumannii in a tertiary hospital, Indonesia.

Acinetobacter baumannii, a pathogen of concern in hospitals worldwide, has diverse antimicrobial resistance mechanisms leading to limiting the antibiotic options and carbapenemase enzyme production is one of the common mechanisms in carbapenem resistance. The epidemiology and resistance pattern of clinical isolates are critical in developing a prevention and treatment strategy. The aim of this was to determine the prevalence and resistance pattern of carbapenem non-susceptible strains (CNS) A. baumannii at Arifin Achmad General Hospital, Pekanbaru, Indonesia. Data were retrieved from the culture and susceptibility test results from various clinical specimens from January 2015 to December 2019. A susceptibility test was conducted using Vitek 2 Compact following the manufacturer's protocol. To explore the genetic profile of CNS A. baumannii, we amplified the blaOXA-23 and blaOXA-51 genes, carbapenemase producing genes, using a duplex polymerase chain reaction (PCR) among 24 isolates Chi-squared was used to assess the factors associated with the presence of CNS A. baumannii. Between 2015-2019, 1.263 A. baumannii isolates were tested and the prevalence of CNS A. baumannii was 50%. The trend decreased from 53% in 2016 to 45% in 2019. The proportion of CNS A. baumannii was higher among samples from patients treated in the Intensive Care Unit (ICU) compared to non-ICU (p < 0.001). The CNS A. baumannii was also more frequently detected from sputum than from non-sputum samples (p = 0.009). CNS A. baumannii were highly resistant to almost all antibiotics and the highest susceptibility was to amikacin, tigecycline, and trimethoprim/sulfamethoxazole with 64%, 53%, and 43%, respectively. The blaOXA-23 gene was detected in 92% of tested CNS A. baumannii isolates. The prevalence of CNS A. baumannii is high at Arifin Achmad Hospital Riau, Indonesia. This is also supported by the high prevalence of the blaOXA-23 gene among tested isolates. Based on the antibiotic susceptibility pattern there are limited antibiotic choices for CNS A. baummannii urging the strengthening of antimicrobial stewardship programs in the country.

Genotyping by Random Amplified Polymorphic DNA Assay of Acinetobacter baumannii Isolated from Blood Culture of Patients with Hematological Malignancies

Relevance. Acinetobacter baumannii is a significant nosocomial pathogen that can cause severe infections, especially in immunocompromised patients. Aims. This study aimed to investigate clonal diversity of A. baumannii isolated from blood culture in hematological patients by random amplified polymorphic DNA assay (RAPD). Materials &amp; Methods. Genotyping of A.baumannii isolated from blood culture in hematological patients in 7 Russian hospitals (2003–2017) was assessed by RAPD-PCR with primer OPA-2 (5’-TGCCGAGCTG-3’). The computer-assisted analysis was performed by using GelJ software by UPGMA method and Dice similarity coefficient for banding patterns comparison. Using a similarity coefficient (SC) of ≥ 65%, the strains were grouped. Based on the similarity coefficient, the strains were determined as genetically related (≥ 80%). Strains had identical RAPD-patterns if the similarity coefficient was 100%. Results. A total of 96 A. baumannii strains were examined, of those 77 (80.2%) were nonsusceptible to carbapenems. Acquired OXA-carbapenemase genes were detected among 79.2% carbapenem non-susceptible strains. RAPD-PCR genotyping revealed 84 RAPD patterns. The four groups (A-D) including 98% strains were defined by similarity coefficient ≥65%. The predominant group A included 58 (60.4%) strains, the C and B groups – had 15 strains (15.6%) each, and the group D – 6 strains (6.3%). A total of 82 (85.4%) genetically related A. baumannii with a similarity coefficient ≥ of 80% were allocated into 20 clusters. Identical RAPD-patterns were defined for 22 strains that belonged to 6 clusters within the group A and 1 cluster within the group B. Strains with identical RAPD-patterns were detected in a single hospital as well as in several hospitals located in different cities. Conclusions. The current study has demonstrated genetic diversity and clonal dissemination of A. baumannii in hematological departments.

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level.

Infection control effectiveness evaluations require detailed epidemiological and microbiological data. We analyzed the genomic profiles of carbapenem-nonsusceptible Pseudomonas aeruginosa (CNPA) strains collected from two intensive care units (ICUs) in the national referral hospital in Jakarta, Indonesia, where a multifaceted infection control intervention was applied. We used clinical data combined with whole-genome sequencing (WGS) of systematically collected CNPA to infer the transmission dynamics of CNPA strains and to characterize their resistome. We found that the number of CNPA transmissions and acquisitions by patients was highly variable over time but that, overall, the rates were not significantly reduced by the intervention. Environmental sources were involved in these transmissions and acquisitions. Four high-risk international CNPA clones (ST235, ST823, ST357, and ST446) dominated, but the distribution of these clones changed significantly after the intervention was implemented. Using resistome analysis, carbapenem resistance was explained by the presence of various carbapenemase-encoding genes (blaGES-5, blaVIM-2-8, and blaIMP-1-7-43) and by mutations within the porin OprD. Our results reveal for the first time the dynamics of P. aeruginosa antimicrobial resistance (AMR) profiles in Indonesia and additionally show the utility of WGS in combination with clinical data to evaluate the impact of an infection control intervention. (This study has been registered at www.trialregister.nl under registration no. NTR5541).IMPORTANCE In low-to-middle-income countries such as Indonesia, work in intensive care units (ICUs) can be hampered by lack of resources. Conducting large epidemiological studies in such settings using genomic tools is rather challenging. Still, we were able to systematically study the transmissions of carbapenem-nonsusceptible strains of P. aeruginosa (CNPA) within and between ICUs, before and after an infection control intervention. Our data show the importance of the broad dissemination of the internationally recognized CNPA clones, the relevance of environmental reservoirs, and the mixed effects of the implemented intervention; it led to a profound change in the clonal make-up of CNPA, but it did not reduce the patients' risk of CNPA acquisitions. Thus, CNPA epidemiology in Indonesian ICUs is part of a global expansion of multiple CNPA clones that remains difficult to control by infection prevention measures.

A retrospective analysis of Pseudomonas aeruginosa bloodstream infections: prevalence, risk factors, and outcome in carbapenem-susceptible and -non-susceptible infections

BackgroundPseudomonas aeruginosa (PA) is a leading cause of nosocomial infections, and carbapenem non-susceptible strains are a major threat to patient safety.MethodsA single center, retrospective comparative analysis of carbapenem-non-susceptible PA (CnSPA) and carbapenem-susceptible PA (CSPA) bloodstream infections (BSIs) was conducted between January 1, 2007, and December 31, 2016. Prevalence and risk factors associated with CnSPA BSIs were examined.ResultsThe study enrolled 340 patients with PA BSIs; 30.0% (N = 101) of patients had CnSPA. High APACHE II scores (≥15), central venous catheterization, and delayed application of appropriate definitive therapy were independently associated with higher risk of mortality in PA BSIs. Multivariate analysis revealed that respiratory disease and exposure to carbapenems within the previous 90 days to onset of BSI were independent risk factors for acquisition of CnSPA BSIs. Overall all-cause 30-day mortality associated with PA BSIs was 26.8% (91/340). In addition, mortality was higher in patients with CnSPA than in those with CSPA (37.6% vs. 22.2%, respectively; P = 0.003). Corticosteroid therapy and delayed receipt of effective definitive therapy were independent risk factors for death from CnSPA BSIs.ConclusionIncreased incidence of CnSPA BSIs was observed during the study period, with higher mortality seen in patients with these infections. Respiratory disease and exposure to carbapenems were independent risk factors for development of CnSPA BSIs. Appropriate definitive therapy reduced mortality rates. BLBLIs were as effective as carbapenems as a treatment for PA BSIs.

СARBAPENEMASE-PRODUCING GRAM-NEGATIVE BACTERIA IN A SPECIALIZED HOSPITAL OF ST. PETERSBURG

Species composition, susceptibility to antimicrobial agents, incidence and type of carbapenemase of carbapenemase-producing gram-negative bacteria, isolated in the Russian Research Centre of Radiology and Surgical Technologies from February 2014 to April 2016 were described. Screening of carbapenem-resistant bacteria was conducted by plating biomaterial on the chromogenic medium (“CHROMagar KPC”, DRG, France), species identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) on the analyzer VITEK MS (bioMé- rieux, France). The sensitivity of gram-negative bacteria to antimicrobial drugs was determined on the analyzer VITEK-2 (bioMérieux), and the obtained results were interpreted in accordance with EUCAST criteria v.6.0, 2016. Genes encoding carbapenemase of KPC, OXA-48/162, VIM, IMP, NDM, OXA-51, OXA40/24, OXA-23 and OXA-58 groups were detected by multiplex real-time PCR (AmpliSens, Russia). 813 clinically relevant bacteria (602 patients) were obtained, including 405 gram-negative, among which 5.2% (21 strain from 16 patients) non-susceptible to meropenem and/or imipenem: Klebsiella pneumoniae (n = 5), Enterobacter cloacae (n = 2), Serratia marcescens (n = 1), Pseudomonas aeruginosa (n = 3), Acinetobacter baumannii (n = 10). Clinical material from 4 patients was infected by up to 3 carbapenem-non-susceptible strains of different species of gram-negative bacteria at the same time. The genes encoding acquired carbapenemases were detected in 84% of the nonsusceptible to carbapenems isolates: in A. baumannii — OXA40/24 (n = 8); in K. pneumoniae — OXA-48 (n = 1), KPC (n = 1) and NDM (n = 2); in P. aeruginosa — VIM (n = 1) and KPC (n = 1); in E. cloacae — KPC (n = 1). OXA-48 carbapenemase was also detected in one carbapenem-sensitive strain of K. pneumonia. All carbapenemase-producing strains had a phenotype of multidrug resistance. The results of the study showed that over the analyzed period, the prevalence of the carbapenem-nonsusceptible strains of gram-negative bacteria were relatively low, but all these strains were multidrug resistant and most of them possessed acquired carbapenemase genes. The species carbapenemnonsusceptible gram-negative bacteria and the types of the detected acquired carbapenemase were typical for Russia. For K. pneumoniae and P. aeruginosa no predominance of any one type of carbapenemase was revealed, while in all strains of A. baumannii the gene of OXA40/24 carbapenemase was found.

SURVEILLANCE of CARBAPENEM NON-SUSCEPTIBLE GRAM NEGATIVE STRAINS and CHARACTERIZATION of CARBAPENEMASES of CLASSES A, B and D in a LEBANESE HOSPITAL.

The production of carbapenem-hydrolyzing enzymes has been recognized as one of the most currently relevant resistance mechanisms in gram negative bacterial isolates, and is being detected in various countries. In Lebanon, carbapenem resistance was studied among gram negative pathogens collected from a university hospital from January to June of years 2011 and 2012. All isolates were subjected to phenotypic tests including antibiotic susceptibility, cloxacillin effect, modified Hodge test, and Etest for metallo-β-lactamase detection. They were also subjected to genotyping by PCR sequencing to characterize β-lactamases. Between January and June 2011, 48 carbapenem non-susceptible strains were collected. Of these, one Klebsiella pneumoniae harbored OXA-48 and insertion sequence IS 1999; four Acinetobacter baumanni harbored simultaneously OXA-23 and GES-11, and three Pseudomonas harbored VIM-2 carbapenemase. Between January and June 2012, 100 carbapenem non-susceptible strains were collected. Of these, one K. pneumoniae harbored simultaneously OXA-48, IS 1999, and an acquired AmpC of the ACC group; four Serratia marcescens harbored OXA-48, while among eight A. baumannii, one strain co-harbored OXA-23 and GES-11, six harbored OXA-23 and one OXA-24. Fifteen P, aeruginosa and two Pseudomonas species harbored VIM-2; two P. aeruginosa strains produced IMP-1 and two others IMP-2. This epidemiological survey demonstrates the presence of carbapenemases of Ambler classes A, B, and D in a Lebanese hospital and indicates increase in the number and variety of such enzymes.

Laboratory evaluation of the CHROMagar KPC medium for identification of carbapenem-nonsusceptible Enterobacteriaceae

CHROMagar KPC was evaluated with 53 carbapenem-nonsusceptible strains. KPC-producing Klebsiella pneumoniae and Enterobacter cloacae grew efficiently and yielded metallic blue colonies (100% sensitivity). Poor or no growth or atypical colony color were evident with KPC-producing Escherichia coli (71.4% sensitivity) and ertapenem-resistant KPC-nonproducing K. pneumoniae (72.7% sensitivity). CHROMagar KPC appears applicable for processing carbapenem-resistant Enterobacteriaceae surveillance specimens, but its performance might possibly be suboptimal in the presence of KPC-negative ertapenem-resistant strains or for detection of KPC-producing E. coli.

Carbapenem-nonsusceptible strains of Klebsiella pneumoniae producing SHV-5 and/or DHA-1 β-lactamases in a Czech hospital

Resistance to carbapenems in enterobacteria is mediated by the production of several types of carbapenemases or by the decreased permeability of the outer membrane, combined with the expression of extended-spectrum beta-lactamases (ESBLs) or AmpC-like cephalosporinases. The objective of this study was to characterize carbapenem-nonsusceptible (C-NS) isolates of Klebsiella pneumoniae in the University Hospital in Plzen (Czech Republic) and compare them with carbapenem-susceptible (C-S) K. pneumoniae isolates from the same patients. Six C-NS K pneumoniae isolates from different patients were collected between January 2007 and June 2008, and from three of these patients, C-S isolates were available for the study as well. The isolates were typed by pulsed-field gel electrophoresis and multilocus sequence typing. beta-Lactamases were analyzed by isoelectric focusing, bioassay, and PCR and sequencing of bla genes. Major porin channels, OmpK35 and OmpK36, were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot; porin genes were amplified and sequenced, and their expression was assessed by reverse transcriptase-PCR. The C-NS isolates belonged to three pulsotypes and to the clone ST11, produced the SHV-5 ESBL and/or DHA-1 AmpC-type cephalosporinase, did not express OmpK36, and had a reduced expression of OmpK35. The C-S isolates differed from their C-NS counterparts only by porin expression profiles.

Resistance of the carbapenems and homology analysis of Pseudomonas aeruginosa in 28 hospitals in China

Objective To investigate the resistance of carbapenems,the production of metallobeta-lactamases(MBLs)and homology analysis of Psendomonas aeruginosa in China.Methods A total of 654 Pseudomonas aeruginosa isolates were collected from 28 hospitals in 16 difierent regions during the period from July 2006 to July 2007 as part of the Nosocomial Pathogen Resistance Surveillance(NPRS).MICs of imipenem and meropenem were determined by agar dilutiom PFGE was used to analyze the molecular epidemiology of carbapenem-resistant strains.MBLs were detected by Etest and PCR among carbapenem-non-sensitive strains.The transcription levels of MBLs were determined by real-time reverse transcriptase(RT)-PCR.Results Of the 645 Pseudomonas aeruginosa strains,245(37.5%)were resistant to imipenem and 183(28.0%)were resistant to meropenem.A total of 275 carbapenemnonsusceptible strains and 259 carbapenem-resistant strains were chosen for further study. Among the carbapenem-nonsusecptible strains,8.73%(24/275)of the strains carrried MBLs genes hy PCR,but only 6.55%(18/275)of the strains were detected as MBls-producers bv MBL Etest. The MBLs relative expression levels of the 6 MBL genotype-positive but phenotype-negative strains were significantly lower than those of the other 18 MBL genotype-and phenotype-positive strains(P＜0.05).The 259 carbapenemresistant Pseudomonas aeruginosa strains were divided into 89 clones by PFGE.The 24 MBL genotypepositive strains collected from 6 cities were divided into 9 clones by PFGE.Conclusions The carbapenems resistance of Pseudomonas aeruginosa is severe in China.Clonal dissemination of Pseudomonas aeruginosa has not been detected throughout China.MBLs are not the major carbapenems resistance mechanism in Pseudomonas aeruginosa. Key words: Pseudomonas aeruginosa; Carbapenems; Drug Resistance,Microbial