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Objectives The emergence of carbapenem-resistant Pseudomonas aeruginosa has become a serious worldwide medical problem. The aim of this study was to determine the genetic and epidemiological properties of carbapenem-resistant P. aeruginosa strains isolated from hospitals in Nepal. Methods A total of 43 carbapenem-resistant P. aeruginosa isolates obtained from patients in two hospitals in Nepal between 2018 and 2020 were analysed. Their whole genomes were sequenced by next-generation sequencing. A phylogenetic tree was constructed from single nucleotide polymorphism (SNP) concatemers. Multilocus sequence typing (MLST) was performed and antimicrobial resistance genes were identified. Results Of the 43 isolates, 17 harboured genes encoding carbapenemases, including IMP-1, IMP-26, KPC-2, NDM-1, VIM-2 and VIM-5, and 12 harboured genes encoding 16S rRNA methylases, including RmtB4 and RmtF2. The carbapenem-resistant P. aeruginosa isolated in Nepal belonged to various sequence types (STs), including ST235 (5 isolates), ST244 (7 isolates), ST274 (1 isolate), ST357 (10 isolates), ST654 (3 isolates), ST664 (1 isolate), ST773 (1 isolate), ST823 (3 isolates), ST1047 (8 isolates), ST1203 (2 isolates) and ST3453 (2 isolates). Conclusion To the best of our knowledge, this is the first molecular epidemiological analysis of carbapenem-resistant P. aeruginosa clinical isolates from Nepal. The findings strongly suggest that P. aeruginosa isolates producing carbapenemases and 16S rRNA methylases have spread throughout medical settings in Nepal.

Introduction: Metallo-β-lactamases (MBLs) play a major role in the resistance of Pseudomonas aeruginosa to carbapenems. We investigated the antibiotic susceptibility patterns and frequency of MBLs genes (blaIMP and blaSPM) in carbapenem-resistant P. aeruginosa clinical isolates in Sari, Iran. Materials and Methods: The isolates were identified using standard microbiological tests, and their antibiotic susceptibility pattern was determined by the disk agar diffusion method according CLSI criteria. Phenotypic identification of MBL-producing strains assessed by the combined disk test (CDT). Then, polymerase chain reaction (PCR) was used to detect the presence of blaIMP and blaSPM genes. Results: The highest and lowest levels of antibiotic resistance were observed against gentamicin (40%) and piperacillin-tazobactam (13%), respectively. Besides, 40 isolates (40%) had the multi-drug resistant (MDR) phenotype, while 5 (12.5%) MDR isolates were resistant to all antibiotics tested. The results of the CDT showed that among 43 carbapenem non-susceptible clinical isolates of P. aeruginosa, 33 (76.74%) isolates were MBL-producing strains. Also, the frequency of the blaIMP gene among 43 carbapenem non susceptible isolates was determined to be 6.97%, while none of these isolates carried the blaSPM gene. Conclusion: Due to the high prevalence of carbapenem-resistant and MDR P. aeruginosa in this study, routine antibiotic susceptibility testing and phenotypic identification of carbapenemase production by this bacterium are necessary for the proper selection of antibiotics.

espanolObjetivo. El objetivo del estudio es identificar los factores de riesgo asociados a infecciones por Pseudomonas aeruginosa resistente a antibioticos carbapenemicos (PARC) y Acinetobacter baumannii resistente a antibioticos carbapenemicos (ABRC) en pacientes adultos a traves de una revision sistematica de la literatura, clasificarlos segun su nivel de importancia y exponer las recomendaciones en el entorno espanol de un panel de expertos. Material y metodos. Se llevo a cabo una revision sistematica de la literatura para identificar los factores de riesgo asociados a PARC o ABRC y posteriormente evaluar cada factor de riesgo por un panel de expertos basandose en la evidencia disponible y su experiencia en la practica clinica. Resultados. Se identificaron 593 articulos incluyendose 29 para PARC y 23 para ABRC. Se identificaron 38 factores de riesgo asociados a PARC y 36 factores de riesgo asociados a ABRC. Tras su evaluacion, para PARC, se clasificaron en: 11 importantes, 10 moderadamente importantes y 15 poco importantes; y para ABRC, 9 importantes, 5 moderadamente importantes y 19 poco importantes. Para ambos patogenos, los factores de riesgo importantes estuvieron relacionados con el uso previo de antibioticos y la hospitalizacion. Conclusion. Se han identificado los principales factores de riesgo asociados a PARC y ABRC mediante una revision de la evidencia disponible. Sin embargo, son necesarios estudios adicionales prospectivos que permitan identificar los pacientes con infecciones por dichos patogenos. EnglishObjective. The aim of the study is to identify risk factors associated to infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) in adult patients through a systematic literature review, classify them according to their importance and provide recommendations by experts in the Spanish context. Material and methods. We developed a systematic literature review to identify risk factors associated to CRPA or CRAB infections and they were evaluated and discussed by a multidisciplinary panel of experts. Results. There were included 29 studies for P. aeruginosa and 23 for A. baumannii out of 593 identified through systematic literature review. We identified 38 risk factors for P. aeruginosa and 36 for A. baumannii. After risk factor evaluation by the panel of experts, results for CRPA were: 11 important, 10 slightly important and 15 unimportant risk factors; and for CRAB were: 9 important, 5 slightly important and 19 unimportant risk factors. For both pathogens, previous use of antibiotics and hospitalization were important risk factors. Conclusion. We could identify the main risk factors associated to CRPA and CRAB through literature review. There is a need for developing additional studies with higher levels of evidence to identify sooner and better infected patients through associated risk factors.

To the Editor, In this journal attempts to circumvent carbapenem resistance of Pseudomonas aeruginosa were recently reported [1]. Among 28 clinical carbapenem-resistant isolates of P. aeruginosa, 1...

IMP-45, a variant of IMP-9, is one of the dominant metallo-β-lactamases (MBLs) in clinical carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates in China. The aim of this study was to investigate the distribution and mechanism of dissemination of blaIMP-45. MBL genes were detected by PCR in 173 non-duplicate CRPA isolates collected from Hospital HS in Shanghai and 605 P. aeruginosa isolates from a multicenter surveillance of blaIMP-45 in China. In total, 17 IMP-45-producers (14 from Hospital HS and 3 from other hospitals) were identified. Molecular typing identified an outbreak of 11 IMP-45-producing ST508 CRPA in the ICU of Hospital HS. Conjugation assays and whole genome sequencing were conducted among IMP-45-producers. Genomic comparison revealed that 16 blaIMP-45-carrying plasmids (9 from this study and 7 from GenBank) shared a similar backbone with IncP-2 blaIMP-9-carrying plasmid pOZ176 but lacked repA-oriV-parAB region. repA2 gene was presented in pOZ176, blaIMP-45-carrying plasmids (17 from this study and 7 from GenBank) and 15 megaplasmids from GenBank. Phylogenetic analysis of repA2 showed that most blaIMP-45-carrying plasmids were clustered into a sublineage separate from the one containing pOZ176. This IncP-2 plasmid sublineage contributed to the dissemination of blaIMP-45 among genetically diverse P. aeruginosa and recruited multiple resistance genes during its evolution.

Introduction: Carbapenem resistant Pseudomonas aeruginosa strains cause serious problems in treatment. A large number of identified metallo-beta-lactamase (MBL) enzymes produced by P. aeruginosa are one of the most important mechanisms in resistance to carbapenems. MBL genes are located on the chromosome or plasmid, and they can easily spread between different bacterial strains. The activities of these enzymes are zinc-dependent, and they are inhibited by ethylenediaminetetraacetic acid (EDTA). Therefore, this advantage is used in MBL identification tests. In this study, it was aimed to determine MBL among P. aeruginosa strains. Materials and Methods: MBL existence was investigated in 35 P. aeruginosa strains accepted to be mildly susceptible/resistant to any of the carbapenem group of antibiotics through phenotypic and genotypic methods. Phenotypic tests were performed as double disk synergy test (DDST), combined disk diffusion tests (CDDT) by using 0.1 M and 0.5 M EDTA, MBL E-test, and modified Hodge test (MHT). blaIMP, blaVIM, blaGIM, blaSIM, blaSPM genes and blaNDM gene were investigated by multiplex polimerase chain reaction (PCR) and PCR, respectively. Escherichia coli ATCC 25922 and P. aeruginosa ATCC 27853 standard bacteria were used in tests. VIM-1, VIM-2, IMP-13, SPM-1, NDM-1 type MBL-producing P. aeruginosa strains were used as positive controls. Results: Among the carbapenems resistant P. aeruginosa isolates, positivity of MBL was found as 54.2% by MBL E-test, 42.8% by DDST, 94.2% and 37.1% by CDDT method using 0.5 M and 0.1 M EDTA, respectively. Modified Hodge test and genotypic method did not detect MBL. Conclusion: In order to correctly evaluate the results of the phenotypic method, the investigation of resistance genes by molecular methods is also required. The most common metallo-beta-lactamase enzymes responsible for resistance to carbapenem in Pseudomonas were not observed. It was thought that different mechanisms might be responsible for the identified carbapenem resistance.

Polymyxin B has been considered to be the last line of defense for life-threatening infections caused by multiple drug resistant gram-negative pathogens, including carbapenem-resistant Pseudomonas aeruginosa (CRPA). The present study analyzed CRPA resistance to polymyxin B in the Suzhou district of China. Additionally, polymyxin B resistance rates were compared in different parts of the world to determine global trends. The present study also assessed the reliability and effectiveness of the Etest® in a clinical setting, as laboratories lack a reliable and efficient susceptibility test for polymyxin B. The susceptibility rate of polymyxin B reached 96.0%, which is in accordance with results obtained from the United States of America, Europe, Africa and the majority of Asian countries. However, the rate of polymyxin B non-susceptibility (resistant or intermediate) in Singapore is 0.53 (95% confidence interval, 0.12-0.93). In addition, the susceptibility rate of polymyxin B determined via Etest® was not significantly increased compared with that determined via broth microdilution (98.0 vs. 96.0%; P=0.558). Essential and categorical agreement rates reached 98.0%. In conclusion, the polymyxin B resistance rate of CRPA isolates is relatively low in the majority of countries, with the exception of Singapore. Furthermore, Etest® may be a reliable clinical method for the measurement of polymyxin B resistance in CRPA isolates.

The emergence and transmission of metallo-β-lactamases are significant public health concerns that threaten the utility of antimicrobial therapy (1, 2).….

To the editor, Pseudomonas aeruginosa is one of the most common causes of health care infection in the United States. Infections are frequently severe with a higher mortality rate than patients wit...

Objective This study focused on carbapenem resistance in Pseudomonas aeruginosa and examined potential ecological correlations with carbapenem use in Japan. Methods The proportion of carbapenem-resistant P. aeruginosa isolates from 2015 and 2016 by prefecture was obtained from the Japan Nosocomial Infections Surveillance system. Data on carbapenem use was obtained from the National Database of Health Insurance Claims. The correlation between the proportion of carbapenem-resistant isolates and carbapenem consumption was assessed in a cross-sectional manner. The study also collected information on other variables including the numbers of physicians, nurses and medical facilities per 100 000 individuals by prefecture. Results Both the proportion of carbapenem-resistant P. aeruginosa isolates and levels of carbapenem use were higher in western Japan. Using a multivariate model, only carbapenem use remained significantly associated with the proportion of carbapenem-resistant isolates. Conclusions Carbapenem use and the proportion of carbapenem-resistant P. aeruginosa isolates were positively correlated. By longitudinal data collection, this approach offers an avenue to establish causal links as the frequency of carbapenem-resistant P. aeruginosa isolates starts to change in the future.

다제내성 P. aeruginosa의 출현과 확산은 전 세계적으로 중요한 문제가 되고 있다. P. aeruginosa에 의한 발병은 일부 몇몇 세포 관련 및 세포외 병독성 인자의 생성에 기인한다. 본 연구에서는 대전지역의 3차 병원에서 분리된 carbapenem 내성 P. aeruginosa를 대상으로 병독성 인자의 분포와 항균제 내성 양상을 조사하였다. 항균제 감수성 시험은 디스크 확산법으로 확인하였고, 병독성 유전자의 분석을 위해 PCR과 염기서열분석을 수행하였다. 또한, 다제내성 P. aeruginosa의 sequence type (ST)은 multilocus sequence typing (MLST)을 통해 확인하였다. 32균주의 carbapenem 내성 P. aeruginosa 중, 14균주(43.8%)가 다제내성이었으며, 주요 ST는 ST235 (10균주, 71.4.%)임을 확인하였다. 병독성 유전자는 32균주 모두에서 확인되었고, 이 중 가장 높은 빈도로 확인된 병독성 유전자는 toxA, plcN, phzM (100.%)이었다. 또한, 32균주는 모두 8개 이상의 병독성 유전자를 가지고 있었으며, 9균주(28.1%)가 15개의 병독성 유전자를 가지고 있었다. exoU 유전자는 다제내성 P. aeruginosa 균주의 71.4%에서 확인되었다. 이러한 결과는 exoU 유전자가 다제내성 P. aeruginosa 균주의 지속성에 대한 예측 표지자가 될 수 있을 것으로 사료된다.

INTRODUCTION: Carbapenem-resistant Pseudomonas aeruginosa has emerged as a life-threatening infectious agent worldwide. Carbapenemase genes are reported to be some of the most common mechanisms for carbapenem resistance in P. aeruginosa. No reports are available from the Kingdom of Bahrain about carbapenem resistance and the underlying cause. In this study, we determined to study the presence of the metallo-beta-lactamase (M β L) genes of VIM family and NDM-1 in carbapenem-resistant P. aeruginosa strains. METHODOLOGY: Fifty carbapenem-resistant P. aeruginosa isolates were obtained from three main hospitals of Bahrain. They were subjected to antimicrobial susceptibility testing by disc diffusion test. Subsequently, MβL was detected by imipenem-ethylene diamine tetraacetic acid (EDTA) combined disc test and conventional polymerase chain reaction. RESULTS: Among 50 P. aeruginosa strains, 40 (80%) were imipenem resistant. Among the 40 imipenem-resistant strains, 35 (87.5%) strains were positive for the imipenem-EDTA combined disc test, and 21 (52%) were carrying MβL genes. Nineteen (47.5%) strains were positive for the VIM gene; one (2.5%) strain was carrying the NDM-1 gene, while one strain was carrying both the VIM and NDM-1 genes. None of the imipenem sensitive strains carried the VIM or NDM-1 gene. CONCLUSION: This is the first study to report the presence of the VIM family gene and NDM-1 genes in imipenem-resistant P. aeruginosa isolates in the Kingdom of Bahrain. The study also confirms the multiple drug resistance by the MβL strains, attention should therefore from now on, be focused on prevention of further spread of such isolates by firm infection control measures, and to reduce its threat to public health.

Background MDR bacteria including carbapenem-resistant Pseudomonas aeruginosa are recognized as an important cause of hospital-acquired infections worldwide. This investigation seeks to determine the molecular characterization and antibiotic resistance genes associated with carbapenem-resistant P. aeruginosa. Methods We conducted WGS and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from August 2011 to March 2015 in three major hospitals in Hanoi, Vietnam. Results We identified three variants of IMP gene, among which blaIMP-15 was the most frequent (n = 34) in comparison to blaIMP-26 (n = 2) and blaIMP-51 (n = 12). We observed two isolates with imipenem MIC >128 mg/L that co-harboured blaIMP-15 and blaDIM-1 genes and seven isolates (imipenem MIC > 128 mg/L) with a blaKPC-1 gene from the same hospital. MLST data shows that these 72 isolates belong to 18 STs and phylogenetic tree analysis has divided these isolates into nine groups. Conclusions Our results provide evidence that not only blaIMP-26 but other IMP variants such as blaIMP-15 and blaIMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminating in healthcare settings in Vietnam. In addition, we report the emergence of two isolates belonging to ST1240 and ST3340 that harboured two important carbapenemase genes (blaIMP-15 and blaDIM-1) and seven isolates belonging to ST3151 of P. aeruginosa that carried the blaKPC-1 gene in Vietnam, which could potentially cause serious restricted availability of treatment options in healthcare settings.

Background: Multidrug-resistant bacteria including carbapenem resistant Pseudomonas aeruginosa are recognised as an important cause of hospital-acquired infections worldwide. To determine the molecular characterisation and antibiotic resistant genes associated with carbapenem-resistant P. aeruginosa. Methods: we conducted whole-genome sequencing and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from 2010 to 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP genes, among which IMP-15 gene was the most frequent (n= 34) in comparison to IMP-26 (n= 2) and IMP-51 (n=12). We observed two isolates with imipenem MIC >128mg/L that co-harboured IMP-15 and DIM-1 genes and seven isolates (imipenem MIC> 128mg/L) with KPC-1 gene from the same hospital. MLST data showed that sequence types (ST) of 72 isolates were classified into 18 STs and phylogenetic tree analysis divided these isolates into nine groups. Conclusion: Our results provide evidence that not only IMP-26, but other variants of IMPs like IMP-15 and IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminated in health care settings in Vietnam. Also, we report the first finding in Vietnam that two isolates belonging to ST1240 and ST3340 harboured two important carbapenemase genes (IMP-15 and, DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa carried the KPC-1 gene, which could be a potential cause of seriously restricted available treatment options in healthcare settings.

Background: Carbapenem resistant Klebsiella pneumoniae (CRKP), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB) pose significant threats to public health. However, the clinical and economic impacts of CRKP, CRPA, and CRAB remain largely uninvestigated in China. This study aimed to examine the clinical and economic burden of CRKP, CRPA, and CRAB compared with carbapenem susceptible cases in China. Method: We conducted a retrospective and multicenter study among inpatients hospitalized at four tertiary hospitals between 2013 and 2015 who had K. pneumoniae, P. aeruginosa, and A. baumannii positive clinical samples. Propensity score matching (PSM) was used to balance the impact of potential confounding variables, including age, sex, insurance, number of diagnosis, comorbidities (disease diagnosis, and Charlson comorbidity index), admission to intensive care unit, and surgeries. The main indicators included economic costs, length of stay (LOS), and mortality rate. Results: We included 12,022 inpatients infected or colonized with K. pneumoniae, P. aeruginosa, and A. baumannii between 2013 and 2015, including 831 with CRKP and 4328 with carbapenem susceptible K. pneumoniae (CSKP), 1244 with CRPA and 2674 with carbapenem susceptible P. aeruginosa (CSPA), 1665 with CRAB and 1280 with carbapenem susceptible A. baumannii (CSAB). After PSM, 822 pairs, 1155 pairs, and 682 pairs, respectively were generated. Compared with carbapenem-susceptible cases, those with CRKP, CRPA, and CRAB were associated with statistically significantly increased total hospital cost ($14,252, p &lt, 0.0001, $4605, p &lt, $7277, p &lt, 0.0001) and excess LOS (13.2 days, p &lt, 5.4 days, p = 0.0003, 15.8 days, p = 0.0004). In addition, there were statistically significantly differences in hospital mortality rate between CRKP and CSKP, and CRAB and CSAB group (2.94%, p = 0.024, 4.03%, p = 0.03), however, the difference between CRPA and CSPA group was marginal significant (2.03%, p = 0.052). Conclusion: It highlights the clinical and economic impact of CRKP, CRPA, and CRAB to justify more resources for implementing antibiotic stewardship practices to improve clinical outcomes and to reduce economic costs.

최근 P. aeruginosa의 carbapenem에 대한 내성은 전 세계적으로 증가하고 있는 실정이다. 특히 metallo-β-lactamases (MBLs)는 carbapenem의 고도 내성에 관여하고 있는 것으로 보고되고 있다. 한편, Sequence type 235 (ST235)는 다제내성 클론으로써 국제적으로 보고되고 있으며, IMP-6와 VIM-2 유전자의 확산에도 관여하는 것으로 알려져 있다. 본 연구에서는 2008년 3월부터 2014년 6월까지, 대전지역의 3차 병원에서 분리된 carbapenem 내성 P. aeruginosa에서 MBL 유전자를 분석하고 이에 대한 역학관계를 조사하고자 하였다. 항균제 감수성 양상은 디스크 확산법으로 확인하였고, MBL 유전자의 분석을 위해 PCR과 염기서열분석을 수행하였다. 더불어, 역학 관계를 조사하기 위해 multilocus sequence typing (MLST)를 실시 하였다. 110 균주의 carbapenem 내성 P. aeruginosa 중, 32균주(29.1%)가 MBL를 생성하였고, IMP-6 (29균주, 90.6%)가 주요하게 확인되었다. VIM-2는 3균주(9.4%)에서 확인되었으며, 모두 ST357로 확인되었다. IMP-6를 생성하는 P. aeruginosa는 모두 다제내성을 보였고, ST235로 확인되었다. ST235 (55균주, 50.0%)는 가장 높은 비율로 확인된 클론이며 7년 동안 지속적으로 확인되었다. 이러한 다제내성 ST235의 확산을 방지하기 위해, carbapenem의 과도한 사용을 제한하고, 지속적으로 모니터링하는 전략이 개발되어야 할 것으로 사료된다.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been considered a major cause of infection and mortality in burn patients, especially in developing countries such as Iran. One of the most common mechanisms of carbapenem resistance is production of metallo-β-lactamases [(MBLs), including Verona Integron-encoded Metallo-beta-lactamase (VIM), imipenemase (IMP), São Paulo metalo-beta-lactamase (SPM), German imipenemase (GIM), New Delhi metallo-beta-lactamase (NDM), Dutch imipenemase (DIM), Adelaide imipenemase (AIM), Seoul imipenemase (SIM), KHM, Serratia metallo-β-lactamase (SMB), Tripoli metallo-β-lactamase (TMB), and Florence imipenemase (FIM)]. Limited information is available on the prevalence of CRPA and MBLs in Iranian burn units. We performed a systematic search by using different electronic databases, including Medline (via PubMed), Embase, Web of Science, and Iranian Database. Of 586 articles published from January 2000 to December 2016, 14 studies reporting the incidence of CRPA and MBLs as detected by molecular methods in burn patients were included in this review. The meta-analyses showed that the prevalence of CRPA, IMP, and VIM was 76.8% (95% CI 67.5-84.1), 13.1% (95% CI 4.7-31.5), and 21.4% (95% CI 14.6-30.1), respectively, in Iranian burn centers and remaining MBLs types have not yet been detected. There was a high prevalence of MBLs and CRPA in Iranian burn centers. Therefore, these measurements should be applied nationally and rigorous infection control measures and antimicrobial stewardship will be the major pillars to control multidrug resistant microorganisms, such as CRPA.

Carbapenem resistance mediated by NDM is particularly gruesome as this carbapenemase can hydrolyze a wide range of β-lactam antibiotics. Aim: This study aims to detect NDM mediated carbapenem resistance in clinical isolates of Pseudomonas aeruginosa. Materials and Methods: 50 multi-drug resistant clinical urinary isolates of Pseudomonas aeruginosa from three major hospitals in Khartoum state Sudan; Khartoum Teaching Hospital, Medical Army Hospital and Omdurman teaching hospital, in period from July 2016 to September 2017, were investigated for carbapenem resistance using standard disc diffusion method and underwent real-time PCR to detect carbapenem resistance gene blaNDM. Data were analyzed using IBM SPSS. Results: 60% were positive for the blaNDM, 82% were resistant to Imipenem and 75% of the samples were resistant to Meropenem. Conclusion: The emergence of carbapenem resistance is a global problem that requires earnest attention. To make the suitable preventive measures, the emergence of these genes must be monitored closely. Our findings revealed that carbapenem-resistant due to the gene blaNDM is accounted for 60% of the cases, and due to lack of proper data documentation about the emergence of this gene in Sudan, these cases to the best of our knowledge are the first to be reported in Sudan.

Objective. To characterize the population structure and determine the genetic mechanisms of carbapenem resistance in nosocomial isolates of P. aeruginosa collected in Moscow in 2012-2016. Materials and methods. Carbapenem-resistant isolates were collected in two pediatric hospitals in Moscow. Antibiotics susceptibility of P. aeruginosa isolates was assessed using the E-tests and disk-diffusion method. Multilocus sequence typing (MLST) was used for genotyping of the isolates. The presence of metallo-betalactamase (MBL) genes was determined using real-time PCR. Results. All isolates had multidrug resistant phenotype. MLST identified 21 unique sequence types (ST). Five sequence types (ST111, ST235, ST446, ST654 and ST2592) prevailed in the population structure, composing 78% of the carbapenem resistant P. aeruginosa. 50 (57%) isolates carried blaVIM-2 gene; the presence of other carbapenemase genes, including blaNDM and blaIMP, was not detected. Conclusions. The genetic structure of carbapenem-resistant P. aeruginosa population is characterized by a diversity of unrelated sequence-types with the predominance of a small number of the high epidemic risk international clones: ST654, ST111 and ST235. The main carbapenem resistance mechanism of P. aeruginosa isolates was the production of VIM-2 carbapenemase.

Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) often results from multiple mechanisms, creating unique phenotypic patterns of resistance including retaining susceptibility to traditional antipseudomonal β-lactams: cefepime (FEP), ceftazidime (CAZ) and piperacillin-tazobactam (TZP). Outcomes of patients with CRPA susceptible to FEP, CAZ and TZP are unclear. Methods The Georgia Emerging Infections Programed performs active, population-based surveillance for CRPA (minimum inhibitory concentration [MIC] ≥ 8 µg/mL for doripenem, imipenem or meropenem) isolated from sterile sites, urine, lower respiratory tracts and wounds in metropolitan Atlanta. We created a retrospective cohort of adults without cystic fibrosis with their first episode of CRPA while hospitalized or hospitalized within 1 week, from 8/2016 – 7/2018. We compared patients with CRPA that remained susceptible to FEP, CAZ and TZP (“susceptible CRPA”) to those that were not (“resistant CRPA”) including multivariable logistic regression for 30-day mortality. Results Among 643 patients, 638 had susceptibility results available for FEP, CAZ or TZP. 60% were male, median age was 65 years, and median Charlson comorbidity index was 2 (Table 1). Most (66%) resided in a hospital or long-term care facility 4 days prior to culture. The most common source was urine (38%). Non-susceptibility to multiple antibiotic classes was common: 523 (81%) for 3 classes and 214 (33%) for 5 classes (Table 2). 220 (34%) patients had susceptible CRPA and compared to patients with resistant CRPA, were more likely to have lived in a private residence, have a community-associated infection, and less likely to be in the ICU previously (Table 1). Patients with susceptible CRPA had a similar crude 30-day mortality (16% vs 12%, p = 0.15) to those with resistant CRPA, but in a multivariable analysis had an increased 30-day mortality (OR 1.9; 95% CI 1.1–3.2). Table 1 (Part 1/2): Characteristics and outcomes of hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) in metropolitan Atlanta, stratified by antipseudomonal β-lactam susceptibility Table 1 (Part 2/2): Characteristics and outcomes of hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) in metropolitan Atlanta, stratified by antipseudomonal β-lactam susceptibility Table 2: Antibacterial susceptibility results for hospitalized patients with carbapenem-resistant Pseudomonas aeruginosa in metropolitan Atlanta Conclusion Over 1/3 of hospitalized patients with CRPA retained susceptibility to other antipseudomonal β-lactams, but had an increased mortality compared to CRPA resistant to other β-lactams. Further research into mechanisms of resistance or antibiotics received might help explain this unexpected finding. Disclosures Jessica Howard-Anderson, MD, Antibacterial Resistance Leadership Group (ARLG) (Other Financial or Material Support, The ARLG fellowship provides salary support for ID fellowship and mentored research training)

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.Funding: NoneDisclosures: None

Augmented renal clearance (ARC) is common in critically ill patients and is associated with subtherapeutic concentrations of renally eliminated antibiotics. We investigated the impact of ARC on bacterial killing and resistance amplification for meropenem and tobramycin regimens in monotherapy and combination. Two carbapenem-resistant Pseudomonas aeruginosa isolates were studied in static-concentration time-kill studies. One isolate was examined comprehensively in a 7-day hollow-fiber infection model (HFIM). Pharmacokinetic profiles representing substantial ARC (creatinine clearance of 250 ml/min) were generated in the HFIM for meropenem (1 g or 2 g administered every 8 h as 30-min infusion and 3 g/day or 6 g/day as continuous infusion [CI]) and tobramycin (7 mg/kg of body weight every 24 h as 30-min infusion) regimens. The time courses of total and less-susceptible bacterial populations and MICs were determined for the monotherapies and all four combination regimens. Mechanism-based mathematical modeling (MBM) was performed. In the HFIM, maximum bacterial killing with any meropenem monotherapy was ∼3 log(10) CFU/ml at 7 h, followed by rapid regrowth with increases in resistant populations by 24 h (meropenem MIC of up to 128 mg/liter). Tobramycin monotherapy produced extensive initial killing (∼7 log(10) at 4 h) with rapid regrowth by 24 h, including substantial increases in resistant populations (tobramycin MIC of 32 mg/liter). Combination regimens containing meropenem administered intermittently or as a 3-g/day CI suppressed regrowth for ∼1 to 3 days, with rapid regrowth of resistant bacteria. Only a 6-g/day CI of meropenem combined with tobramycin suppressed regrowth and resistance over 7 days. MBM described bacterial killing and regrowth for all regimens well. The mode of meropenem administration was critical for the combination to be maximally effective against carbapenem-resistant P. aeruginosa.

Introduction: Nosocomial infections caused by Pseudomonas aeruginosa producing carbapenemases represent an important cause of morbidity and mortality among immunosuppressed patients. The aim of our study was to detect the production of metallo-carbapenemases (MBLs) by phenotypic methods and to detect the presence of the MBLs encoding genes (blaIMP and blaVIM) by PCR in P. aeruginosa strains isolated from hospitalized patients to the Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca. Material and methods: Between September 2014-February 2015, we tested thirty-eight P. aeruginosa strains resistant to carbapenems according to CLSI 2014 breakpoints, determined by Vitek®2(BioMérieux),isolated from various clinical specimens. Phenotypic detection of the MBLs production was performed using the KPC/MBL Confirmation kit (ROSCO®) and the MBL Etest® IP/IPI (BioMérieux). We used the PCR method for detecting MBLs encoding genes: blaIMP, blaVIM. Results: The strains were obtained from surgery (55.3%), ICU (15.8%) and gastroenterology wards (28.9%), isolated from pus (25.8%), tracheal secretion (22.7%), bile (13.6%), sputum (10.6%), blood (10.6%), other secretions (16.7%). These strains were resistant to multiple classes of antibiotics. By ROSCO® method 28/38 strains (73.7%) were positive with imipenem ± dipicolinic acid (DPA) and 22/38 (57.9%) with meropenem ± DPA. Etest® waspositive for the 28/38 strains (73.7%). 11 strains (28.9%) were positive for KPC with the screening method. We identified: 6 blaIMP+ (15.8%), 2 (5.3%) blaVIM+ and 4 blaIMP+/blaVIM+ strains (10.5%). Conclusion: Both genes encoding MBL were found, alone or in combination. The increasing level of carbapenem resistance of these strains impose their routine testing to detect MBL.

Pseudomonas aeruginosa (PA) is a major cause of healthcare-associated infections. Antipseudomonal carbapenems are among the antimicrobial agents used to treat PA infections, but several mechanisms of resistance, including the production of a carbapenemase (CP), may compromise their clinical efficacy. The objectives of this study were to determine: (i) the dissemination of carbapenem-resistant CP-negative and CP-positive PA isolates; and (ii) the in-vitro activity of ceftolozane-tazobactam (CTT) against carbapenem-susceptible and carbapenem-resistant isolates. Isolates were collected prospectively from January 2016 to April 2017 at 20 German medical laboratories. Each centre was asked to provide 50 consecutive isolates from hospitalized patients. Overall, 985 isolates were collected, of which 34% were obtained from intensive care patients. Seven hundred and thirty-eight (74.9%) isolates were susceptible to both imipenem and meropenem (Subgroup I), and 247 (25.1%) isolates were resistant to carbapenems (Subgroup II): 125 (12.7%) were imipenem-resistant but meropenem-susceptible, 12 (1.2%) were meropenem-resistant but imipenem-susceptible, and 110 (11.2%) were resistant to both carbapenems (Subgroup III). A CP was detected in 28 (2.8%) isolates (predominantly VIM-2). Nine hundred and fifty (96.4%) isolates were CTT-susceptible. Susceptibility to CTT was seen in 99.6% of Subgroup I isolates, 87% of Subgroup II isolates and 74.5% of Subgroup III isolates. Overall, 2.8% of PA produced a CP, while 22.2% were carbapenem-resistant, CP-non-producing isolates. Based on these findings, CTT may be considered for treatment of PA infections, particularly those caused by multi-drug-resistant CP-non-producing isolates.

Background Between January 2015 and July 2017, we investigated the frequency of carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Pseudomonas aeruginosa (CRPA) at the Mulago Hospital intensive care unit (ICU) in Kampala, Uganda. Carbapenemase production and carbapenemase gene carriage among CRAB and CRPA were determined; mobility potential of carbapenemase genes via horizontal gene transfer processes was also studied. Methods Clinical specimens from 9269 patients were processed for isolation of CRAB and CRPA. Drug susceptibility testing was performed with the disk diffusion method. Carriage of carbapenemase genes and class 1 integrons was determined by PCR. Conjugation experiments that involved blaVIM positive CRAB/CRPA (donors) and sodium azide resistant Escherichia coli J53 (recipient) were performed. Results The 9269 specimens processed yielded 1077 and 488 isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. Of these, 2.7% (29/1077) and 7.4% (36/488) were confirmed to be CRAB and CRPA respectively, but 46 were available for analysis (21 CRAB and 25 CRPA). Majority of specimens yielding CRAB and CRPA were from the ICU (78%) while 20 and 2% were from the ENT (Ear Nose & Throat) Department and the Burns Unit, respectively. Carbapenemase assays performed with the MHT assay showed that 40 and 33% of CRPA and CRAB isolates respectively, were carbapenemase producers. Also, 72 and 48% of CRPA and CRAB isolates respectively, were metallo-beta-lactamase producers. All the carbapenemase producing isolates were multidrug resistant but susceptible to colistin. blaVIM was the most prevalent carbapenemase gene, and it was detected in all CRAB and CRPA isolates while blaOXA-23 and blaOXA-24 were detected in 29 and 24% of CRAB isolates, respectively. Co-carriage of blaOXA-23 and blaOXA-24 occurred in 14% of CRAB isolates. Moreover, 63% of the study isolates carried class 1 integrons; of these 31% successfully transferred blaVIM to E. coli J53. Conclusions CRAB and CRPA prevalence at the Mulago Hospital ICU is relatively low but carbapenemase genes especially blaVIM and blaOXA-23 are prevalent among them. This requires strengthening of infection control practices to curb selection and transmission of these strains in the hospital.

Background China launched a 3-year rectification scheme for the clinical use of antibiotics in 2011, and a specific scheme for carbapenem use in 2017. The aim of this study was to investigate the effects of government policies on carbapenem use, and their correlation with carbapenem-resistant Pseudomonas aeruginosa (CRPA). Methods The study was divided into four stages: preintervention (2010), antimicrobial programme (2011–2013), post-antimicrobial programme (2014–2016) and carbapenem programme (2017). A point-score system was proposed for evaluating the rationality of carbapenem use, and evaluated based on the indications, microbial culture, single dose, interval, and duration. Any prescription without a global score of 10 points was judged as irrational. The trend was analyzed by regression analysis, and Spearman correlation analysis was used for testing the correlation. Findings The rate of rational use of carbapenems was 29.7% in 2010, and increased by 55.5, 45.2, and 51.5% during the subsequent three stages. The rationality declined slightly during the post-antimicrobial programme (2014–2016) while the consumption of carbapenems was markedly increased. These two parameters improved slightly in 2017. Moreover, the prevalence of CRPA was significantly negatively correlated with the rate of rational carbapenem use (Coefficient = − 0.553, P 0.05). Conclusions The rational application of carbapenems was related to government policies in this study, with irrational carbapenem use possibly related to the development of CRPA. The current point-score system could be a useful tool for performing assessments.

In the current study carbapanem-resistant P. aeruginosa bloodstream infection (CRPA-BSI) was associated with high 14-day mortality. Although, highly resistant to meropenem, half of the isolates achieved in vitro synergy with the combination of meropenem with colistin, and the patients that received this combination therapy showed a tendency towards lower mortality. Our strains did not carry exoU gene, on the other hand, patients with CRPA-BSI caused by strains harboring gene lasB evolved more frequent to death.

Background This study aimed to estimate the impact of carbapenem-resistant Pseudomonas aeruginosa (CRPA) on clinical and economic outcomes in a Chinese tertiary care hospital. Methods Patients were assigned to a carbapenem-susceptible P aeruginosa group or to a CRPA group and matched using propensity score matching. In-hospital mortality, length of stay (LOS), LOS after culture, total hospital costs, daily hospital cost, and 30-day readmission were comparatively analyzed. Subgroup analysis was performed to determine the associations between the subgrouping factors and in-hospital mortality in patients with CRPA isolates. Results Within the propensity-matched cohort, in-hospital mortality (12.6% vs 7.8%; P = .044), LOS (median 29.0 vs 25.5 days; P = .026), LOS after culture (median 18.5 vs 14.0 days; P = .029), total hospital costs (median $6,082.0 vs $4,954.2; P = .015), and daily hospital cost (median $236.1 vs $223.6; P = .045) were significantly higher in CRPA patients than in carbapenem-susceptible P aeruginosa patients. Subgroup analysis revealed a significant interaction between CRPA and age (P = .009). Conclusion Prevention and control of CRPA among hospitalized patients, especially among those over the age of 65 years, is a good measurement for the reduction of mortality and medical costs derived from CRPA infection or colonization.

Background Nosocomial infections due to CR-PA are associated with significant morbidity and mortality, and knowledge of epidemiology and underlying mechanisms of antimicrobial resistance is critical to addressing this threat. Recently, we identified a CR-PA of sequence type (ST) 309 resistant to all available β-lactams due to acquired β-lactamases as a potential emerging clone. To assess the evolving landscape of resistance in CR-PA we performed a cross-sectional survey of historical and contemporary isolates utilizing phenotypic testing and whole-genome sequencing (WGS). Methods Historical CR-PA isolates (n = 61, collected from 1999 to 2015) and contemporary isolates (n = 110, collected from 2017 to 2018) from a large urban hospital network in Houston, TX were tested for susceptibility to meropenem, aztreonam (ATM), ceftolozane/tazobactam (C/T), and ceftazidime/avibactam (CZA) using E-test on Mueller–Hinton (MH) agar. WGS for all isolates was performed on a MiSeq platform (Illumina). Data analysis was performed using a custom analysis pipeline, including Tseemann MLST tool, Resfinder, and Abricate using the CARD database. Results The prevalence of resistance across all β-lactams tested increased in contemporary strains as compared with that of historical strains (Figure 1). Among important contemporary antipseudomonal antibiotics C/T, ATM, and CZA, resistance increased from 0%, 22%, and 5% to 15%, 44%, and 16%, respectively (Figure 1). WGS revealed that ST235 was the most common sequence type, followed by ST111 in the historical collection (Figure 2). In contrast, a larger degree of genetic diversity was found in contemporary isolates, with the emergence of multidrug-resistant clones such as ST308 (2%) and ST309 (3%). Resistance to C/T was associated with acquired β-lactamases in 88% (14/16) of isolates, including VIM-2, GES-19/GES-26, VEB-1, NMD-1, and OXA enzymes. Conclusion Resistance to newer agents C/T and CZA markedly increased in contemporary CR-PA strains. While the epidemic clones ST235 and ST111 were the most frequent STs, ST308 and 309 have emerged among contemporary MDR isolates. Most concerning was the association of C/T resistance and the acquisition of β-lactamases, due to the potential for further dissemination. Disclosures All authors: No reported disclosures.

Background To estimate the impact of antimicrobials stewardship in the temporary evolution of the Density Incidence of Pseudomonas aeruginosa resistant to carbapenems (DI_PaCRE). Methods In Modena Policlinico, a tertiary care hospital, from September 2014, universal rectal screening and antibiotic stewardship (ABS) focusing on carbapenem sparing strategy were introduced. We used the statistical approach already described (A nonlinear time-series analysis approach to identify thresholds in associations between population antibiotic use and rates of resistance. López-Lozano JM, et al. Nat Microbiol. 2019 Apr 8. doi: 10.1038/s41564-019–0410-0) in order to adjust a non-linear model (Multivariate Adaptive Regression Splines) looking for the identification and estimation of thresholds in the influence of the use of Carbapenems on the DI_PaCRE. Results We identified a threshold at 5.65 DDD/100 bed-days of Carbapenems (CarbUse). Indeed, above this threshold, for every increase of one DDD/100 bed-days, the DI_PaCRE increased by 0.15 new cases by 1000 bed-days. On the basis of our analyses, considering a typical course of 7 days of treatment, an average CarbUse of 6.5 DDD/100 bed-days in 2012 and 2013, for an average of 15000 monthly bed-days, means around 139 treated patients. In order to avoid the emergence of resistance, the threshold was equivalent to a maximum number of 121 patients to be treated. Below this threshold, i.e in 2018, CarbUse including 66 patients treated did not select antimicrobial resistance. Conclusion PaCRE could be controlled by reducing the use of carbapenems below minimum thresholds of 6.5 DDD/100 bed-days. In order to avoid the onset of resistance to carbapenems in Pseudomonas aeruginosa, less than 121 patients per month should receive this class of drug. This finding could provide innovative approach to guide antimicrobial stewardship strategy focused on limit the spread of PaCRE in hospital populations. Disclosures All authors: No reported disclosures.

The aim of the present study was to investigate the molecular mechanism of carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates recovered from Libyan hospitals between April 2013 and April 2014. In total, 49 strains (24 P. aeruginosa and 25 A. baumannii) were isolated, including 21 P. aeruginosa and 22 A. baumannii isolates (87.75%) resistant to imipenem (minimum inhibitory concentrations ≥16 μg/ml). The blaVIM-2 gene was detected in 19 P. aeruginosa isolates. All imipenem-resistant P. aeruginosa isolates showed the presence of OprD mutations. Acquired OXA-carbapenemase-encoding genes were present in all A. baumannii isolates: blaOXA-23 (n=19) and blaOXA-24 (n=3). Finally, a total of 13 and 17 different sequence types were assigned to the 21 P. aeruginosa and the 22 A. baumannii carbapenem-resistant isolates, respectively. This study is the first report describing imipenem-resistant P. aeruginosa and A. baumannii isolated from patients in Libya. We report the first case of co-occurrence of blaVIM-2 with oprD porin loss in identical isolates of P. aeruginosa in Libya and demonstrate that these oprD mutations can be used as a tool to study the clonality in P. aeruginosa isolates. We also report the first identification of multidrug-resistant A. baumannii isolates harboring blaOXA-23-like, blaOXA-24-like, and blaOXA-48-like genes in Libya.

The aim of this study was to evaluate the antimicrobial activity of imipenem plus amikacin or polymyxin B against six carbapenem-resistant P. aeruginosa by time-kill assay. Synergism was observed in two isolates for combinations with amikacin. For combinations with polymyxin B, synergism and antagonism also occurred in two isolates.

OBJECTIVES To investigate the molecular characteristics and epidemiology of metallo-β-lactamase-producing Pseudomonas aeruginosa from urine of urinary tract infection patients in Hyogo Prefecture, Japan. METHODS Carbapenem-resistant P. aeruginosa isolated from the urine of 21 urinary tract infection patients in three general hospitals in Hyogo Prefecture (Japan) were collected between 2007 and 2014. Their antibiotic susceptibilities, metallo-β-lactamase screening test, metallo-β-lactamase gene sequencing, multilocus sequence typing and repetitive-sequence-based polymerase chain reaction were determined for epidemiological analyses to investigate the genetic characteristics. RESULTS Out of 21 isolates, 13 (61.9%) were positive for metallo-β-lactamase. There were 11 (52.4%) isolates with IMP-1 in them, one (4.5%) isolate with IMP-7 and one (4.5%) isolate with VIM-1. Metallo-β-lactamase-positive isolates were mainly identified as ST235, and metallo-β-lactamase-negative isolates were STs 357, 277, 234, 439 and 639. Repetitive-sequence-based polymerase chain reaction showed metallo-β-lactamase-positive isolates were grouped in eight clusters, and ST235 isolates with IMP-1 from three hospitals belonging to the identical group I, the other ST235 isolates with IMP-7 and VIM-1 were from two hospitals belonging to group II. CONCLUSIONS Metallo-β-lactamase-positive P. aeruginosa of ST235 isolates with IPM-1 were mainly identified from the urine of urinary tract infection patients in Hyogo, Japan. A ST235 isolate with VIM-1 was found for the first time. Further investigation is necessary to follow the spread of metallo-β-lactamase-positive isolates.

The aim of this study was to assess the prevalence of acquired carbapenemase genes amongst carbapenem non-susceptible Pseudomonas aeruginosa isolates in Australian patients with cystic fibrosis (CF). Cross-sectional molecular surveillance for acquired carbapenemase genes was performed on CF P. aeruginosa isolates from two isolate banks comprising: (i) 662 carbapenem resistant P. aeruginosa isolates from 227 patients attending 10 geographically diverse Australian CF centres (2007-2009), and (ii) 519 P. aeruginosa isolates from a cohort of 173 adult patients attending one Queensland CF clinic in 2011. All 1189 P. aeruginosa isolates were tested by polymerase chain reaction (PCR) protocols targeting ten common carbapenemase genes, as well the Class 1 integron intI1 gene and the aadB aminoglycoside resistance gene. No carbapenemase genes were identified among all isolates tested. The intI1 and aadB genes were frequently detected and were significantly associated with the AUST-02 strain (OR 24.6, 95% CI 9.3-65.6; p 0.0001) predominantly from Queensland patients. Despite the high prevalence of carbapenem resistance in P. aeruginosa in Australian patients with CF, no acquired carbapenemase genes were detected in the study, suggesting chromosomal mutations remain the key resistance mechanism in CF isolates. Systematic surveillance for carbapenemase-producing P. aeruginosa in CF by molecular surveillance is ongoing.

Background Pseudomonas aeruginosa is one of the most common Gram-negative pathogen causing nosocomial infection worldwide. The emergence of multi-drug resistant strains has become a major clinical concern in recent years. Resistance-nodulation-cell division (RND) family efflux pumps play an important role in the development of multidrug resistance in P. aeruginosa. Objectives The aims of the present study were to evaluate the antimicrobial susceptibility against carbapenems used and to evaluate the gene expression of two resistance nodulation cell division-type efflux pump systems (MexB and MexY) among carbapenem non-susceptible P. aeruginosa. Methods A total of 256 non-repetitive P. aeruginosa were collected from the different clinical samples of patients admitted in Qazvin and Tehran educational hospitals. Antimicrobial susceptibility testing was performed by standard Kirby-Bauer method. The expression of MexB and MexY genes was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Results In total, 107 (41.8%) isolates were non-susceptible to imipenem and/or meropenem. All carbapenem non-susceptible isolates were positive for the presence of MexB and MexY genes. The expression of MexB (P value = 0.004) and MexY (P value = 0.001) genes was significantly increased, compared to standard carbapenem sensitive strains. Conclusions The findings of the present study showed the considerable presence of carbapenem resistance among the clinical isolates of P. aeruginosa. The overexpression of MexB and MexY genes is also established among these resistant isolates collected from studied hospitals in Iran.

Background/purpose: The incidence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) related healthcare-associated infection (HAI) has increased in recent year worldwide. This study is to investigate the risk factors associated with CRPA infections in a university hospital setting in Taiwan to provide more information for clinician and infection control system. Methods: A retrospective cross-sectional study was conducted from January 1st, 2009 to June 30th, 2014. Patients with P. aeruginosa related HAI were included and divided into the CRPA case group and carbapenem-susceptible Pseudomonas aeruginosa (CSPA) control group. The medical records were reviewed to identify risk factors for CRPA HAI and mortality. Patients with prior use of any anti-pseudomonal carbapenems were included in subgroup analysis. Results: 395 cases of P. aeruginosa infection were enrolled from total of 3263 HAI events; 63 were CRPA and 332 were CSPA. The prevalence of CRPA was 15.9% (63/395). Significant risk factors related to CRPA infection were longer time at risk, prior use of anti-pseudomonal carbapenems, and prior use of aminoglycoside (p