Imipenem-resistant Pseudomonas Aeruginosa Research Articles

Prevalence of Imipenemase and Verona Integron-Encoded Metalloβ-Lactamase in Imipenem-Resistant Pseudomonas aeruginosa

Objective: To determine the prevalence of metallo-β-lactamase (MBL) including imipenemase (IMP) and Verona integronencoded metallo-β-lactamase (VIM) in imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates and investigate the in vitro activities of 9 antimicrobial agents against MBL-positive isolates. Material and Methods: Seventy-eight IRPA isolates were obtained from Songklanagarind Hospital. MBL production was detected by the combined-disk test, and the blaIMP and blaVIM genes were determined via Polymerase Chain Reaction (PCR). The in vitro activities of amikacin, gentamicin, aztreonam, ceftazidime, meropenem, ciprofloxacin, colistin, piperacillin/ tazobactam, and ticarcillin/clavulanate were determined using the E-test method. Results: Of the 78 IRPA isolates, 20 (25.6%, 95% CI 17.2-36.4%) were MBL phenotype-positive, and 30 (38.5%, 95% CI 28.5-49.6%) were MBL genotype-positive (29 Imipenemase (IMP)-type and 1 Verona integron-encoded metallo-βlactamase (VIM)-type). Ninety percent of the MBL genotype-positive isolates were MDR. Most MBL genotype- positive isolates were susceptible to colistin (susceptibility rate of 96.7% and MIC50 value of 1.5 µg/mL). Conclusion: Our results showed a high prevalence of MBL-positive isolates (38.5%) in IRPAs, and the IMP-type isolates were dominant among the metallo-β-lactamase-producing imipenem-resistant P. aeruginosa tested. Most MBL-positive isolates were susceptible to colistin and had low MIC50 values.

In vitro Effects of Various Antimicrobials Alone and in Combinations against Imipenem-Resistant Pseudomonas aeruginosa

Imipenem-resistant Pseudomonas aeruginosa (IRPA) infection is a serious problem in hospitals. Combination therapy is an alternative treatment for this infection. In this study, the in vitro activities of amikacin, aztreonam, ceftazidime, ciprofloxacin, colistin, imipenem, and piperacillin/tazobactam alone and in various combinations were determined by E-test for 38 imipenem-resistant P. aeruginosa isolates obtained from a Thai hospital. Of the 38 IRPA isolates, 9 (24%) were low-level IRPA (defined as MICs of imipenem 8-32 μg/mL) and 29 (76%) were high-level IRPA (defined as MICs of imipenem >32 μg/mL). The high-level IRPA isolates were susceptible to colistin (90%), piperacillin/tazobactam (72%), and amikacin (52%). The low-level IRPA isolates were susceptible to colistin (100%) and all other antimicrobials tested (78%-89%). The MIC50 value of colistin against both the high-level and low-level IRPA isolates was 1.5 μg/mL. Of all the antimicrobial combinations tested, ceftazidime plus ciprofloxacin displayed the highest percentages of synergistic effects against IRPA isolates (26%, 10/38 isolates) and a high percentages of synergistic effects against high-level IRPA isolates (21, 6/29 isolates), with no antagonistic effects detected. Colistin had the greatest activity against most IRPA isolates among all of the antimicrobials tested, while ceftazidime plus ciprofloxacin showed promise in treating infections caused by IRPA isolates including high-level IRPAs.

Changes in antimicrobial susceptibility of commonly clinically significant isolates before and after the interventions on surgical prophylactic antibiotics (SPAs) in Shanghai.

Surveillances and interventions on antibiotics use have been suggested to improve serious drug-resistance worldwide. Since 2007, our hospital have proposed many measures for regulating surgical prophylactic antibiotics (carbapenems, third gen. cephalosporins, vancomycin, etc.) prescribing practices, like formulary restriction or replacement for surgical prophylactic antibiotics and timely feedback. To assess the impacts on drug-resistance after interventions, we enrolled infected patients in 2006 (pre-intervention period) and 2014 (post-intervention period) in a tertiary hospital in Shanghai. Proportions of targeted pathogens were analyzed: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), imipenem-resistant Escherichia coli (IREC), imipenem-resistant Klebsiella pneumoniae (IRKP), imipenem-resistant Acinetobacter baumannii (IRAB) and imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates. Rates of them were estimated and compared between Surgical Department, ICU and Internal Department during two periods. The total proportions of targeted isolates in Surgical Department (62.44%, 2006; 64.09%, 2014) were more than those in ICU (46.13%, 2006; 50.99%, 2014) and in Internal Department (44.54%, 2006; 51.20%, 2014). Only MRSA has decreased significantly (80.48%, 2006; 55.97%, 2014) (p < 0.0001). The percentages of VRE and IREC in 3 departments were all <15%, and the slightest change were also both observed in Surgical Department (VRE: 0.76%, 2006; 2.03%, 2014) (IREC: 2.69%, 2006; 2.63%, 2014). The interventions on surgical prophylactic antibiotics can be effective for improving resistance; antimicrobial stewardship must be combined with infection control practices.

Systematic review and meta-analysis of imipenem-resistant Pseudomonas aeruginosa prevalence in Iran.

Imipenem-resistant Pseudomonas aeruginosa (IRPA), due to resistance to different classes of antibiotics and its remarkable capacity to survive in harsh and adverse conditions such as those in the hospital environment, is considered a serious threat to the healthcare system. Given the great impact of IRPA on patients' outcome and in order to possibly improve antibiotic prescription, this study was conducted to determine the prevalence of clinical isolates of IRPA in different parts of Iran. A systematic literature search was performed in PubMed, Web of Science, Google Scholar and Scopus, as well as in two Iranian domestic search engines, i.e., Iranian Scientific Information Database and Magiran. Finally, after applying exclusion and inclusion criteria 37 articles with full-texts describing the prevalence of imipenem-resistant P. aeruginosa were selected for meta-analysis and systematic review. The pooled estimation of 5227 P. aeruginosa isolates in this analysis showed that the percentage of imipenem-resistant P. aeruginosa is about 54% in the Iranian population (95%CI: 0.47-0.62, logit event rate=0.19, 95%CI: -0.12,0.49). The findings of this analysis show that in the majority of Iranian hospitals the relative frequency of IRPA is high, therefore, in order to prevent further dissemination of IRPA, more appropriate antibiotic prescription and infection control policies must be implemented by decision-makers.

Study on the resistance mechanism via outer membrane protein OprD2 and metal β-lactamase expression in the cell wall of Pseudomonas aeruginosa.

The aim of the present study was to evaluate the imipenem-resistant mechanism via the outer membrane protein (OMP) OprD2 and metal β-lactamase expression in the cell wall of Pseudomonas aeruginosa. The Pseudomonas aeruginosa was clinically separated and validated by VITEK-2 full-automatic bacteria analyzer. Drug resistance, sensitive antibiotics and minimum inhibitory concentration (MIC) were tested using the drug sensitivity analysis system. The phenotype positive strains of MBL genes were screened using the Kirby-Bauer diffusion method by adding metal ion-chelating agent EDTA on the imipenem susceptibility paper. IMP-1, VIM-1 and SPM metaloenzyme genes were tested by polymerase chain reaction (PCR)-telomeric repeat amplification protocol (TRAP). The OMP OprD2 genes were tested by PCR-TRAP, and the protein expression was tested using western blot analysis. The location of OMP OprD2 was confirmed using the sodium salicylate inhibition test. The results showed that 80 portions (40%) of MBL-positive strains were screened out of 200 specimens. Imipenem-resistant Pseudomonas aeruginosa (IRPA) and MIC values were significantly higher than quality control bacteria and control bacteria (P<0.05). A total of 35 cases with IMP-1 positive, 20 with VIM-1 positive, 16 with SPM positive, 5 with 2 positive genes and 4 with 3 positive genes were screened among MBL positive strains. A total of 150 portions (75%) of OprD2 deficiencies were screened from 200 specimens. The standard strains and sensitive strains showed OprD2 protein bands at 45 kDa while no OprD2 protein bands appeared in OprD2 deficiency strains. It was in accordance with gene detection. In conclusion, OMP OprD2 deficiency and MBL phenotype positivity may be important mechanisms of IRPA.

Overproduction of active efflux pump and variations of OprD dominate in imipenem-resistant Pseudomonas aeruginosa isolated from patients with bloodstream infections in Taiwan.

BackgroundThe emergence of imipenem-resistant Pseudomonas aeruginosa (IRPA) has become a great concern worldwide. The aim of this study was to investigate resistance mechanisms associated with bloodstream isolated IRPA strains in Taiwan.ResultsA total of 78 non-duplicated IRPA isolates were isolated from patients with bloodstream infection. The average prevalence of imipenem-resistance in those isolates was 5.9 % during a 10-year longitudinal surveillance in Taiwan. PFGE results showed high clonal diversity among the 78 isolates. VIM-2, VIM-3, OXA-10, and OXA-17 β-lactamases were identified in 2 (2.6 %), 3 (3.8 %), 2 (2.6 %), and 1 (1.3 %) isolates, respectively. Active efflux pumps, AmpC β-lactamase overproduction, and extended-spectrum AmpC cephalosporinases (ESACs) were found in 58 (74.4 %), 25 (32.1 %) and 15 (19.2 %) of IRPA isolates, respectively. oprD mutations with amino acid substitution, shortened putative loop L7, premature stop codon caused by point mutation, frameshift by nucleotide insertion or deletion, and interruption by insertion sequence were found in 19 (24.4 %), 18 (23.1 %), 15 (19.2 %), 14 (17.9 %), and 10 (12.8 %) of isolates, respectively.ConclusionsThis study suggests that alterations in the OprD protein and having an active efflux pump are the main mechanisms associated with bloodstream isolated IRPA. Overproduction of AmpC, ESACs, and the presence of VIM- and OXA-type β-lactamases play additional roles in reduced susceptibility to imipenem in P. aeruginosa isolates in Taiwan.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0719-2) contains supplementary material, which is available to authorized users.

Characterization of carbapenem resistance mechanisms and integrons in Pseudomonas aeruginosa strains from blood samples in a French hospital.

Metallo-β-lactamases (MBLs), porin OprD, integrons, virulence factors and the clonal relationships were characterized in imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates. Fifty-six IRPA strains were recovered from blood samples of different patients at a Toulouse teaching hospital from 2011 to 2013. Susceptibility testing of 14 antibiotics was performed by the disc diffusion method. Detection and characterization of MBLs, the oprD gene and integrons were studied by PCR and sequencing. Thirteen genes involved in the virulence of P. aeruginosa were analysed. Molecular typing of IRPA strains was performed by PFGE and multilocus sequence typing. In this study, 61 % of the IRPA isolates showed a multi-resistance phenotype. The MBL phenotype, detected in three isolates (5.4 %), was linked to the blaVIM-2 gene. The oprD gene was amplified in 55 (98.2 %) IRPA strains, and variations were observed in 54 of them. Insertion sequences (IS) truncating oprD were detected in eight IRPA strains, with the novel ISPa56 identified in two strains. Class 1 integrons were detected in 24 (42.9 %) IRPA strains. The blaVIM-2 gene was found inside the class 1 integron arrangements. The new integrons In1054 (intI1-aacA56-qacEΔ1-sul1) and In1160 (intI1-aacA4-aacC1d-ISKpn4-gcuE-qacEΔ1-sul1) have been described for the first time, to the best of our knowledge, in this study. A high clonal diversity was found in our strains. Among the variety of sequence types (STs) found, ST175, ST233, ST235, ST244 and ST654 were noteworthy as epidemic clones. In conclusion, 5.4 % of IRPA strains showed an MBL phenotype linked to the blaVIM-2 gene. The identified oprD high polymorphism could be implicated in the variable resistance to carbapenems in IRPA strains. The dissemination of high-risk clones is a cause of concern.

Risk factors for imipenem-resistant Pseudomonas aeruginosa infection in neonatal intensive care unit

Objective To determine the risk factors for imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in neonatal intensive care unit (NICU).Methods One hundred and eighty-eight Pseudomonas aeruginosa infected children (confirmed by pathogenic examination) in the NICU of Maternal and Child Health Hospital of Guangdong from January 1,2008 to December 31,2011,were chosen as the objects of study,and were divided into two groups.The first group included 73 children that had been isolated with IRPA strains(IRPA group),and the second group included 115 children that only had imipenem-sensitive Pseudo monas aeruginosa (ISPA) strains (ISPA group).Chi-square test or t-test was applied.The risk factors were investigated by univariate or multivariate Logistic regression analysis.Results Data from univariate analysis showed that the gestational age and birth weight of neonates were lower than those in ISPA group [(34.0±3.5) weeks vs (35.6±2.8)weeks,t=3.413,P＜0.01; (1848.1±276.4) g vs (2110.7±345.6) g,t=5.472,P＜0.01].There were more neonates with gestational age ≤ 32 weeks [67.1％ (49/73) vs 45.2 ％ (52/115)],birth weight ＜1500 g [73.9％ (54/73) vs 33.0％(38/115)],small for gestational age [68.5％ (50/73) vs 29.6％ (34/115)],receiving imipenem [72.6％ (53/73) vs 27.0％ (31/115)] or the third generation cephalosporins [65.8％ (48/73) vs 33.0％ (38/115)] two weeks before the isolation of Pseudomonas aeruginosa,and mechanical ventilation [78.1％ (57/73) vs 61.7 ％ (71/115)],deep vein catheterization [83.6％(61/73) vs 65.2％(75/115)] in the IRPA group than in the ISPA group (all P＜0.05 or 0.01).The multivariate Logistic regression analysis revealed that imipenem treatment within two weeks before the isolation of Pseudomonas aeruginosa (OR=6.409; 95％ CI:1.926-21.333,P =0.002) was an independent risk factor.Conclusions IRPA infection in NICU hospitalized infants is strongly related to their gestational age and birth weight.History of imipenem administration could be an independent risk factor. Key words: Pseudomonas aeruginosa ; Pseudomonas infections; Imipenem; Drug resistance,bacterial ; Cross infection; Intensive care units, neonatal ; Risk factors

Risk Factors for Development of Intestinal Colonization with Imipenem-Resistant Pseudomonas aeruginosa in the Intensive Care Unit Setting

Risk factors for development of intestinal colonization by imipenem-resistant Pseudomonas aeruginosa (IRPA) may differ between those who acquire the organism via patient-to-patient transmission versus by antibiotic selective pressure. The aim of this study was to quantify potential risk factors for the development of IRPA not due to patient-to-patient transmission.

Analysis of integrons and associated gene cassettes of metallo-β-lactamase-positive Pseudomonas aeruginosa in Malaysia

In this study, 90 non-replicate imipenem-resistant Pseudomonas aeruginosa (IRPA) Malaysian isolates collected between October 2005 and March 2008 were subjected to a screening test for detection of the integron and the gene cassette. Class 1 integrons were detected in 54 IRPA clinical isolates, whilst three isolates contained class 2 integrons. Analysis of the gene cassettes associated with the class 1 integrons showed the detection of accC1 in isolates carrying bla(IMP-7) and aacA7 in isolates carrying bla(VIM-2). aadA6 was detected in two isolates carrying bla(IMP-4). Using random amplification of polymorphic DNA analysis, 14 PCR fingerprint patterns were generated from the 32 isolates carrying metallo-β-lactamase (MBL) genes (35.5 %), whilst 20 patterns were generated from the 58 non-MBL gene isolates (64.4 %). Based on the differences in the fingerprinting patterns, two clusters (A and B) were identified among the MBL-producing isolates. Cluster A comprised 18 isolates (56 %) carrying the bla(VIM) gene, whereas cluster B comprised 14 (44 %) isolates carrying the bla(IMP) gene. The non-MBL isolates were divided into clusters C and D. Cluster C comprised 22 non-MBL isolates harbouring class 1 integrons, whilst cluster D consisted of three isolates carrying class 2 integrons. These findings suggest that the class 1 integron is widespread among P. aeruginosa isolated in Malaysia and that characterization of cassette arrays of integrons will be a useful epidemiological tool to study the evolution of multidrug resistance and the dissemination of antibiotic resistance genes.

Metallo-β-lactamase–producing imipenem-resistant Pseudomonas aeruginosa clinical isolates in a university teaching hospital in Malaysia: detection of IMP-7 and first identification of IMP-4, VIM-2, and VIM-11

Ninety ( n = 90) imipenem-resistant Pseudomonas aeruginosa (IRPA) clinical isolates collected randomly during 2005 to 2008 from University Malaya Medical Center were assessed for the presence of different variants of metallo-β-lactamase (MBL) genes. Polymerase chain reaction (PCR) assay detected 32 ( n = 32) MBL gene PCR-positive isolates with the presence of bla IMP gene in 14 ( n = 14) and bla VIM in 18 ( n = 18) isolates. Four allelic variants, bla IMP-7 (12 isolates), bla IMP-4 (2 isolates), bla VIM-2 (17 isolates), and bla VIM-11 (1 isolate), of MBL genes were identified. This study is the first report of detection of bla IMP-4, bla VIM-2, and bla VIM-11 MBL genes from IRPA clinical isolates in Malaysia.

Imipenem-resistant Pseudomonas aeruginosa gastrointestinal carriage among hospitalized patients: risk factors and resistance mechanisms

Risk factors for imipenem (IMP)-resistant Pseudomonas aeruginosa (IRPA) digestive carriage were analyzed, and genetic events contributing to select resistant isolates in patients exposed to IMP were investigated. Among the 150 patients with hospital-acquired P. aeruginosa digestive carriage, 38 isolates were IRPA. DNA pulsotypes revealed 16 distinct clones. In 4 patients, a second P. aeruginosa isolate showed resistance to IMP compared with the initial susceptible isolate. By comparing the different oprD sequences between IMP-susceptible P. aeruginosa and IRPA strains, a genetic event was systematically found for each resistant isolate, leading to either the absence of OprD or a truncated porin. The multivariate analysis demonstrated that prior IMP exposure was associated with IRPA carriage. In summary, we confirmed that IMP use selects for IRPA in the gut flora. Cross-transmission, however, was frequently observed in intensive care units. Combining epidemiologic approach and molecular analysis is a powerful tool to delineate mechanisms of emerging resistance.

The Role of Patient‐to‐Patient Transmission in the Acquisition of Imipenem‐ResistantPseudomonas aeruginosaColonization in the Intensive Care Unit

Imipenem-resistant Pseudomonas aeruginosa (IRPA) is an emerging problem. The causal role of antibiotic selective pressure versus patient-to-patient transmission has not been assessed using a large cohort. Patients who were admitted to the medical and surgical intensive care units (ICUs) at the University of Maryland Medical Center from 2001 through 2006 had multiple perianal culture samples collected. Using pulsed-field gel electrophoresis (PFGE), the number of patients who acquired IRPA as a result of patient-to-patient transmission was determined. We also analyzed a subset of patients who had a previous surveillance culture that grew an imipenem-susceptible P. aeruginosa (ISPA) and a subsequent culture that grew IRPA. Our cohort consisted of 7071 patients. Three hundred patients were colonized with IRPA. 151 patients had positive culture findings at ICU admission, and 149 patients acquired an IRPA. Among the patients who acquired IRPA, 46 (31%) had a PFGE pattern similar to that for another isolate, and 38 (26%) were found to be colonized with an ISPA on the basis of earlier culture results. Of the 38-patient subset, 28 (74%) had identical PFGE patterns. Our data showed that, of those cases of IRPA acquisition, 46 (31%) were defined as cases of patient-to-patient transmission, and 28 (19%) were cases of acquisition by the patients' endogenous flora.

Imipenem-resistant Pseudomonas aeruginosa infection at a medical-surgical intensive care unit: Risk factors and mortality

Objectives The aim of this study was to evaluate the risk factors and attributable mortality associated with imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in a medical-surgical intensive care unit (ICU). Methods A retrospective case-control study was carried out at a 16-bed medical-surgical ICU in a 780-bed, university-affiliated hospital. All patients admitted from January 1, 2003, to December 31, 2004, who had nosocomial infection caused by IRPA, were included in the study. Results Imipenem-resistant P. aeruginosa was recovered from 63 patients during the study period. One hundred eighty-two controls were matched with cases by period of admission, age, and time at risk. Urinary tract (34.9%) and respiratory tract (22.2%) were the main sources of IRPA isolation. In multivariate analysis, a previous stay in the ICU (odds ratio, 3.54; 95% confidence interval [CI], 1.29-9.73; P = .03) was the only independent risk factor for IRPA infection. The in-hospital mortality rate among case patients was 49% (31 of 63) compared with 33% (61 of 182) for control patients (odds ratio, 1.92; 95% CI, 1.07-3.44; P = .02). Thus, we had an attributable mortality of 16% (95% CI, 9.74%-22.3%; P = .03). Conclusions Our study suggests that IRPA infections are strongly related to previous ICU stay, and that IRPA infections significantly increase mortality in those critical patients.

Imipenem-Resistant Pseudomonas aeruginosa : Risk Factors for Nosocomial Infections

The aim of this study was to determine the risk factors for nosocomial infections of imipenem-resistant Pseudomonas aeruginosa (IRPA). A prospective case-control study was performed at a tertiary care hospital in Ankara from January to December 2004. The patients with nosocomial P. aeruginosa infection were included in the study. The features of the patients with IRPA infections were compared to those with imipenem-sensitive P. aeruginosa (ISPA) infections. Only the first isolation of P. aeruginosa was considered. Nosocomial infections were defined according to Center for Disease Control (CDC) criteria. IRPA was isolated from 75 (44.1%) patients, and ISPA was isolated from 95 (55.9%) patients during the study period. IRPA were most frequently isolated from endotracheal aspirate (19%) cultures (p=0.048), whereas ISPA were most frequently isolated from urine (28%) cultures (p=0.023). In multivariate analysis, a longer duration of hospital stay until P. aeruginosa isolation (odds ratio [OR], 1.027; 95% confidence interval [CI], 1.002-1.054, p=0.034), arterial catheter administration (OR, 2.508; 95% CI, 1.062-5.920, p=0.036), vancomycin (OR, 2.882; 95% CI, 1.130-7.349, p=0.027), piperacillin-tazobactam (OR, 6.425; 95% CI, 2.187-18.875, p=0.001), and imipenem (OR, 3.580; 95% CI, 1.252-10.245, p=0.017) treatment within the 14 days before isolation of IRPA were independently associated with imipenem resistance. It was concluded that treatment with imipenem, vancomycin and piperacillin-tazobactam were major risk factors for IRPA infections in hospitalized patients. The nosocomial occurrence of IRPA was also strongly related to the duration of hospital stay, arterial catheter administration.

Use of bacteriophage in the treatment of experimental animal bacteremia from imipenem-resistant Pseudomonas aeruginosa

The emergence of antibiotic-resistant bacterial strains still remains a significant problem for antimicrobial chemotherapy in the clinic. Bacterial viruses (bacteriophages or phages) have been suggested to be used as alternative therapeutic agents for bacterial infections. However, the efficacy of phage therapy in treating drug-resistant infections in humans is uncertain. Therefore in the present study, we examined the effectiveness of phages in the treatment of imipenem-resistant Pseudomonas aeruginosa (IMPR-Pa) infection in an experimental mouse model. Twenty-nine strains of phage were isolated from our hospital sewage, and phage ØA392 was representatively used for all testing because it has lytic activity against a wide range of clinical isolates of IMPR-Pa. We found that intraperitoneal (i.p.) injections of one IMPR-Pa strain (3 x 10(7) CFU) caused bacteremia and all mice died within 24 h. A single i.p. inoculation of the phage strain (MOI > or =0.01) at up to 60 min after the bacterial challenge was sufficient to rescue 100% of the animals. This lifesaving effect coincided with the rapid appearance of ØA392 in the circulation (within 2 h after i.p. injection), which remained at substantially higher levels for up to 48 h until the bacteria were eradicated. However, the survival rates of the mice dropped to approximately 50% and 20% when the same dose of this purified phage preparation was administered at 180 min and 360 min, respectively, after IMPR-Pa infections. In addition, we demonstrated that the ability of this phage to rescue bacteremic animals was due to the functional capabilities of the phage and not to a non-specific immune effect. The protection from death occurred only in animals inoculated with bacteria-specific virulent phage strains. When the heat-inactivated phages were used, the survival rate of the infected mice was dramatically reduced to 20% or lower. Moreover, the levels of the antibody against the phage were not significantly changed at the time when the bacteremic animals were protected by the active phages. Finally, our observations revealed that the inoculation of the mice with high-doses of ØA392 alone produced no adverse effects attributable to the phage. These data indicate that phages can save animals from pernicious P. aeruginosa infections and suggest that phage therapy may be potentially used as a stand-alone therapy for patients with IMPR-Pa infections.

The risk factors for acquisition of imipenem-resistant Pseudomonas aeruginosa in the burn unit

Objective: This study was conducted to determine the risk factors for acquisition of imipenem-resistant Pseudomonas aeruginosa (IRPA) in the burn unit. Methods: Patients hospitalized in the burn unit from July 2003 to November 2004 were included in this study. The features of patients with isolated IRPA were compared with those of patients with isolated imipenem-susceptible P. aeruginosa (ISPA). Demographic features, total burn surface area (TBSA), burn depth, antimicrobials used in 15-day period before isolation, and presence of IRPA in the unit at the same period were included in the risk factors analysis. Results: P. aeruginosa was recovered from 133 patients in this period, 93 were IRPA and 40 were ISPA. There was no significant difference between patients with ISPA and patients with IRPA in terms of age, TBSA, and burn depth. In multivariate logistic regression analysis, hospital stay before isolation (odds ratio (OR): 3.6), carbapenem usage (OR: 7.4), broad-spectra antibiotic usage (OR: 6.5), previous presence of ISPA in the patient (OR: 1.7) and presence of IRPA in the unit at the same period (OR: 2.6) were independent risk factors for acquisition of IRPA. Conclusion: Long hospitalization time, previous imipenem/meropenem use, previous broad-spectra antibiotic use, previous presence of ISPA in a patient and presence of IRPA in a unit at the same period were associated with acquisition of IRPA in the burn unit. In order to decrease the incidence of IRPA isolation, the usage of broad-spectra antibiotics, especially carbapenem, should be restricted, hospitalization time should be shortened if possible, and universal isolation precautions should be strictly applied to prevention cross-contamination.

Serial changes in ICU-acquired pneumonia pathogen after the remodeling of the environment in a MICU

The aim of the study was to observe effects of the improvement of the patient's care facility in a medical ICU (MICU) on ICU-acquired pneumonia (IAP), especially caused by drug-resistant bacteria including methicillin-resistant Staphylococcus aureus, third-generation cephalosporin-resistant Acinetobacter baumanii (ISAB), imipenem-intermediate sensitive A. baumanii (IIAB), imipenem-resistant A. baumanii (IRAB), expanded-spectrum beta-lactamase (ESBL), and imipenem-resistant Pseudomonas aeruginosa (IRPA).

Clinical surveillance of surgical imipenem-resistant Pseudomonas aeruginosa infection in a Japanese hospital

In order to elucidate any changes in imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in Japan, we examined 511 P. aeruginosa stains isolated from our surgical ward between 1987 and 2001. These isolates were subjected to susceptibility testing against various antipseudomonal agents including imipenem, meropenem, ceftazidime, gentamicin and ciprofloxacin. They were serotyped with the slide agglutination test and genotyped using pulsed-field gel electrophoresis (PFGE). The annual incidences of IRPA infections were particularly high in the early 1990s. Epidemiological investigations revealed that these outbreaks were due to dissemination of hospital-acquired IRPA isolates. Intensive use of imipenem promoted the selection of highly resistant strains. Further study of resistance mechanisms revealed that none of the 110 IRPA strains were metallo-β-lactamase (MBL) producers. Polymerase chain reaction (PCR) analysis using bla IMP specific primers confirmed that no IMP-1 type MBL gene-positive strains were detected from our ward. Susceptibilities of those IRPA strains against other antipseudomonal agents showed relatively low levels, suggesting that imipenem resistance was mainly due to impermeability of the OprD porin. In conclusion, hospital-acquired outbreaks of IRPA were recently reduced by guidelines for, and surveillance of, appropriate use of antimicrobial agents. When the rate of IRPA isolation increases, serotyping should be performed initially and PFGE is required to confirm outbreaks. A computer-assisted genotyping technique is available to perform epidemiological studies of IRPA isolates.

Risk Factors for Imipenem-Resistant Pseudomonas aeruginosa among Hospitalized Patients

Risk factors for the nosocomial recovery of imipenem-resistant Pseudomonas aeruginosa (IRPA) were determined. A case-control study design was used for the comparison of 2 groups of case patients with control patients. The first group of case patients had nosocomial isolation of IRPA, and the second group had imipenem-susceptible P. aeruginosa (ISPA). Control patients were selected from the same medical or surgical services from which case patients were receiving care when isolation of IRPA occurred. Risk factors analyzed included antimicrobials used, comorbid conditions, and demographic variables. IRPA was recovered from 120 patients, and ISPA from 662 patients. Imipenem (odds ratio [OR], 4.96), piperacillin-tazobactam (OR, 2.39), vancomycin (OR, 1.80), and aminoglycosides (OR, 2.19) were associated with isolation of IRPA. Vancomycin (OR, 1.64), ampicillin-sulbactam (OR, 2.00), and second-generation cephalosporins (OR, 2.00) were associated with isolation of ISPA. Antibiotics associated with ISPA are different from antibiotics associated with IRPA. The OR for imipenem as a risk factor for IRPA is less than that reported from studies in which control group selection was suboptimal.