Patient-to-Patient Transmission of Acinetobacter baumannii Gastrointestinal Colonization in the Intensive Care Unit.

Acinetobacter baumannii is an important nosocomial pathogen. The objective of this study was to determine the proportion of A. baumannii infections due to patient-to-patient transmission by analyzing the molecular epidemiology of patients who acquired A. baumannii, using perianal surveillance cultures in a large 2-year intensive care unit (ICU) population. The design was a prospective cohort study. Patients who were admitted to the medical and surgical intensive care units at the University of Maryland Medical Center from 2011 to 2013 underwent admission, weekly, and discharge perianal culture collection. Using multilocus sequence typing (MLST) with subsequent pulsed-field gel electrophoresis (PFGE) for increased discrimination, combined with hospital overlap, the number of patients that acquired A. baumannii due to patient-to-patient transmission was determined. Our cohort consisted of 3,452 patients. In total, 196 cohort patients were colonized with A. baumannii; 130 patients were positive at ICU admission, and 66 patients acquired A. baumannii during their stay. Among the 196 A. baumannii patient isolates, there were 91 unique MLST types. Among the 66 patients who acquired A. baumannii, 31 (50%) were considered genetically related by MLST and/or PFGE type, and 11 (17%) were considered patient-to-patient transmission by genetic relatedness and overlapping hospital stay. Our data show that, of those cases of A. baumannii acquisition, at least 17% were cases of patient-to-patient transmission.

In Vivo Efficacy of Relebactam (MK-7655) in Combination with Imipenem-Cilastatin in Murine Infection Models.

The World Health Organization has identified antimicrobial resistance as a global public health threat since the prevalence and spread of antibiotic resistance among bacterial pathogens worldwide are staggering. Carbapenems, such as imipenem and meropenem, have been used to treat multidrug-resistant bacteria; however, since the development of resistance to carbapenems, ß-lactam antibiotics in combination with ß-lactamase inhibitors (BLI) has been one of the most successful strategies to enhance the activity of ß-lactam antibiotics. Relebactam (REL) is a new BLI which has been found to inhibit class A and class C ß-lactamases in vitro REL has been reported to restore imipenem's activity against both imipenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae Reported here are the in vivo efficacy studies of the imipenem-cilastatin (IMI)-REL combination in mouse models of disseminated and pulmonary infection caused by imipenem-resistant clinical isolates of P. aeruginosa and K. pneumoniae The combination was also evaluated in a P. aeruginosa delayed pulmonary model of infection. IMI-REL was found to be effective in the disseminated model of infection with log reduction in P. aeruginosa CFU of 3.73, 3.13, and 1.72 at REL doses of 40, 20, and 10 mg/kg, respectively. For K. pneumoniae, log reductions in CFU of 2.36, 3.06, and 2.29 were reported at REL doses of 80, 40, and 20 mg/kg, respectively. The combination was less effective in the delayed pulmonary model than in the immediate pulmonary model; however, overall REL was found to be effective against these imipenem-resistant strains.

Imipenem Resistant Pseudomonas aeruginosa: The fall of the final quarterback.

OBJECTIVE: To isolate, determine the frequency, and study the demographic trends of MBL positive Pseudomonas aeruginosa from imipenem resistant isolates collected from clinical samples in a tertiary care hospital of Pakistan. METHODS: In this cross sectional study a total of 230 strains of Pseudomonas were isolated from various clinical specimens on the basis of culture and biochemical tests. Imipenem resistant isolates were selected by Kirby Bauer Diffusion technique, followed by screening for MBL production by Imipenem EDTA Combined Disk Test. Demographic details of each patient were recorded on a separate questionnaire. Chi-Square goodness-of-fit test was computed to review the isolation of MBL positive isolates (P-value ≤ 0.05) in different specimen. RESULTS: Out of 230 strains of P. aeruginosa 49.5% were imipenem resistant; MBL production was confirmed in 64.9% of the resistant isolates. Resistance to polymyxin B (12.5%) was notable. Majority of the MBL positive strains were isolated from patients aged between 20-39 years (45.9%) and the predominant source was pus (43.24%) which was found to be statistically significant (P-value=0.04). Outpatient departments (24.3%) and burn unit (21.6%) were the major places for resistant isolates. CONCLUSION: MBL production is one of the major causes of IRPA. Increasing resistance to polymyxin B is grave. Due to acquisition of MBL strains MDR P. aeruginosa has become endemic in tertiary setups.

Epidemiology of VIM-1-imipenem resistant Pseudomonas aeruginosa in Iran: A systematic review and meta-analysis.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic human pathogen which causes serious problems, especially in people who have immunodeficiency. Metallo beta-lactamase (MBL) resistance in this bacterium has led some difficulties in treating bacterial infections. MBLs are being reported with increasing frequency worldwide. The aim of the present systematic review and meta-analysis was to collect data about the relative frequency (RF) of VIM-1-imipenem resistant P. aeruginosa (VIM-1-IRPA) in different regions of Iran and report an overall prevalence if possible. MATERIALS AND METHODS: PubMed, ISI web of science, Scopus and Google Scholar were searched using following key terms: "P. aeruginosa," "imipenem," "VIM-1" and "Iran" were. Articles/abstracts, which used clinical specimens and had done polymerase chain reaction to detect the VIM-1 gene of MBL genes, were included in this review. STATA SE version 11.2 (StataCorp, College Station, TX, USA) was used for statistical analysis. RESULTS: Out of 5457 results found, 10 articles were eligible to be included in our systematic review and meta-analysis. These studies were carried out in Tehran, Isfahan, Kurdistan, Ahvaz, Markazi and Northwest of Iran (Orumieh and Tabriz). Pooled estimation of 1972 P. aeruginosa samples showed that 13% (95% confidence interval = 10.5-16.5%]) of strains were VIM-1 positive. VIM-1-IRPA RF in different studies varied from 0% to 19.5% in Isfahan and Markazi provinces, respectively. We found a moderate heterogeneity (Chochran Q-test, P = 0.032, I-squared = 50.7%) of VIM-1-IRPA RF among studies. CONCLUSION: According to the results of this study VIM-1-IRPA RF in Iran is in low-level Prevention strategies to reduce the prevalence rates of VIM-1 positive strains in Iran are needed.

Colistin-induced structural and biochemical changes in carbapenem-resistant Acinetobacter baumannii isolated from the hospital environment.

BACKGROUND: Acinetobacter baumannii is an emerging multidrug-resistant bacterium and is considered as one of the important causes of nosocomial infections. OBJECTIVES: The main objectives are to determine the drug-resistant pattern of beta-lactamase-producing A. baumannii, colistin-induced structural and biochemical changes. METHODS: A. baumannii strains were isolated from the restrooms using the selective media, viz., restroom door, restroom floor, washing area, and restroom tap. A total of 120 samples were collected from all four sampling sites. These strains and their drug-resistance patterns were identified. Then carbapenem-resistance was analyzed and the occurrence of the drug-resistant gene (blaOXA-23) was determined. Colistin was applied at various concentrations (20 - 100 µg/mL) and the molecular mechanism of A. baumannii was analysed. RESULTS: The bacterial population was high on doors (53 ±â€¯2 CFU/mL), followed by restroom tap (19 ±â€¯1 CFU/mL), restroom floor (14 ±â€¯3 CFU/mL), and washing area (3 ±â€¯0 CFU/mL), respectively. A total of 343 A. baumannii strains were isolated from the 120 samples obtained for one year from the restroom. The isolated bacteria showed resistance to selected carbapenems, with 100% isolates being resistant to imipenem, followed by cefotaxime (1.4 ±â€¯0.2% susceptibility). More blaOXA-23 gene carrying strains were isolated from restroom tap(89 ±â€¯2.1%) than other sources. Colistin exhibited bactericidal activity against drug-resistant A. baumannii. Treating A. baumannii strain with 100 µg/mL colistin induced cell membrane roughness in vitro. Scanning Electron Microscopy (SEM) analysis revealed moderate cell shrinkage after treatment with colistin. Bacterial cells treated with hydrogen peroxide or colistin for 30 min induced the production of hydroxyl radicals. The bacterial lysis increased fluorescence and hydroxyl radicals, and released cellular protein and sugars. CONCLUSIONS: The isolated A. baumannii was resistant to imipenem and showed susceptibility to colistin. Colistin disrupted cell membrane in drug-resistant A. baumannii in vitro. The regular screening for drug-resistance among A. baumannii strains can help monitor the outbreak of A. baumannii and manage control measures.

In vitro evaluation of antimicrobial combinations against imipenem-resistant Acinetobacter baumannii of different MICs.

BACKGROUND: This study was designed to verify the effectiveness of antimicrobial combination therapy against Acinetobacter baumannii isolates with different degrees of resistance to imipenem. METHODS: A total of twenty-one isolates with imipenem MICs of 16µg/ml (fifteen isolates) or 64µg/ml (six isolates), as identified using the Vitek II system, were included in this study. The MICs of all the isolates to each drug were confirmed again using the broth microdilution method, and a checkerboard assay was used for the assessment of the in vitro effectiveness of various antibiotic combinations. RESULTS: The results of susceptibility testing for single antibiotics indicated that imipenem-resistant Acinetobacter baumannii isolates exhibited good sensitivity to tigecycline and minocycline yet poor sensitivity to colistin, cefoperazone/sulbactam and levofloxacin. The distribution range of MICs for doripenem ranged from 0.5µg/ml to 128µg/ml, and the MICs ranged from 2µg/ml to 32µg/ml for levofloxacin. For combinations of imipenem and colistin, synergy was observed for the fourteen isolates with imipenem MICs of 16µg/ml and one isolate with an imipenem MIC of 64µg/ml. For the combinations of imipenem and cefoperazone/sulbactam, synergy was only observed for the fifteen isolates with imipenem MICs of 16µg/ml. The combinations of imipenem and fosfomycin showed synergy for twelve isolates with imipenem MICs of 16µg/ml. Other antimicrobial combinations based on colistin did not exhibit obvious synergy. CONCLUSION: The high sensitivity of tigecycline and minocycline in this study provides a reference for the clinical treatment of imipenem-resistant Acinetobacter baumannii infections in our region. The effectiveness of combination therapy may be predicted by the imipenem MICs of the isolates. The effect of fosfomycin in the combinations also reflects the clinical value of old drugs for new uses. These results suggest us that if we use carbapenem antibiotics in combination, more attention should be paid to the MICs of single drugs, and the economic costs should also be considered.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Identification and characteristics of imipenem-resistant Acinetobacter baumannii in surgical wards in a Chinese university hospital.

The aim of this study was to investigate the prevalence and characteristics of imipenem-resistant Acinetobacter baumanni isolated from surgical wards in a university hospital, China. A total of 143 non-duplicate A. baumannii were isolated from 517 inpatients in surgery intensive care units (ICUs), burn wards, and general surgery wards. Of these, 102 isolates of A. baumannii (71.3%) were resistant to imipenem. Among imipenem-resistant isolates, all isolates were resistant to almost all antimicrobial agents except polymyxin E, all isolates were positive for blaOXA-23 and blaOXA-51 in addition to ISAba1, 52 (51%) were positive for blaOXA-58, 8 (7.8%) contained blaVIM-2, which co-harbored with blaOXA-58. Molecular typing revealed the presence of three clones among imipenem-resistant isolates. This study confirmed that A. baumannii strains harboring OXA or VIM type ß-lactamases are widely distributed throughout the surgery wards. The data demonstrate that there was a high prevalence of imipenem-resistant A. baumannii infection in the region.

Nosocomial emerging of (VIM1) carbapenemase-producing isolates of Klebsiella pneumoniae in North of Iran.

BACKGROUND AND OBJECTIVES: The rapid emergence and dissemination of carbapenemase-producing Klebsiella pneumoniae strains and other members of the Enterobacteriaceae poses a considerable threat to the care of hospitalized patients and to public health. The aim of this study was to determine the frequency of metallo-ß-lactamases (MBL) and VIM-1 gene in multidrug-resistant strains of K. pneumoniae. METHODS: 50 isolates of non - duplicated K. pneumoniae cultured from patients at intensive care units were tested for their susceptibilities to 13 different antibiotics using microbroth dilution assay. Isolates showing resistance to at least one of the carbapenems were checked for production of metallo-ß-lactamase (MBLs) using imipenem-EDTA synergy tests. PCR was used to detect the gene encoding VIM-1 metallo-ß-lactamase (MBL). RESULTS: Of 50 clinical isolates, 26 (52%) were resistant to imipenem in disk diffusion method. Using imipenem-EDTA synergy tests, production of MBL was detected in 15 (30%) isolates. PCR assay showed that 15 isolates were positive for VIM and these included 10 and 5 isolates showing positive and negative results in phenotypic method of MBL detection test respectively. Amikacin was found as the most effective antibiotic against the MBL producers in this study. CONCLUSION: The emergence of bla(VIM-1) producing K. pneumoniae in North of Iran is concerning. Microorganisms producing bla(VIM-1) constitute the prevalent multidrug-resistant population of K. pneumoniae in that region.

Fatal pneumonia and empyema thoracis caused by imipenem-resistant Nocardia abscessus in a cancer patient.

We describe a case of pneumonia and empyema thoracis caused by trimethoprim-sulfamethoxazole-susceptible, but imipenem-resistant Nocardia abscessus in a cancer patient. The isolate was confirmed to the species level by 16S rRNA sequencing analysis. The patient did not respond to antibiotic therapy, including ceftriaxone and imipenem, and died of progressing pneumonia and multiple organ failure.

Spread of imipenem-resistant Acinetobacter baumannii co-expressing OXA-23 and GES-11 carbapenemases in Lebanon.

OBJECTIVES: The acquisition of carbapenemases by Acinetobacter baumannii is reported increasingly worldwide, but data from Lebanon are limited. The aims of this study were to evaluate the prevalence of imipenem-resistant A. baumannii in Lebanon, identify resistance determinants, and detect clonal relatedness. METHODS: Imipenem-resistant A. baumannii were collected from nine Lebanese hospitals during 2012. Antimicrobial susceptibility, the cloxacillin effect, and ethylenediaminetetraacetic acid (EDTA) synergy were determined. Genes encoding carbapenemases and insertion sequence ISAba1 were screened via PCR sequencing. ISAba1 position relative to genes encoding Acinetobacter-derived cephalosporinases (ADCs) and OXA-23 was studied by PCR mapping. Clonal linkage was examined by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR). RESULTS: Out of 724 A. baumannii isolated in 2012, 638 (88%) were imipenem-resistant. Of these, 142 were analyzed. Clavulanic acid-imipenem synergy suggested carbapenem-hydrolyzing extended-spectrum ß-lactamase. A positive cloxacillin test indicated ADCs, while EDTA detection strips were negative. Genotyping indicated that 90% of isolates co-harbored blaOXA-23 and blaGES-11. The remaining strains had blaOXA-23, blaOXA-24, blaGES-11, or blaOXA-24 with blaGES-11. ISAba1 was located upstream of blaADC and blaOXA-23 in 97% and 100% of isolates, respectively. ERIC-PCR fingerprinting revealed 18 pulsotypes spread via horizontal gene transfer and clonal dissemination. CONCLUSION: This survey established baseline evidence of OXA-23 and GES-11-producing A. baumannii in Lebanon, indicating the need for further surveillance.

Antimicrobial activities of Saudi honey against Pseudomonas aeruginosa.

UNLABELLED: Five types of imported and local honey were screened for both their bacteriocidal/bacteriostatic activities against both Imipenem resistant and sensitive Pseudomonas aeruginosa in both Brain Heart infusion broth and Mueller-Hinton agar. The results indicated that the effect was concentration and type of honey dependant. All types of honey tested exerted a full inhibition of bacterial growth at the highest concentration tested of 50% at 24 h of contact. The inhibitory effect of honey on bacterial growth was clear with concentrations of 20% and 10% and this effect was most evident in the case of Manuka honey as compared to Nigella sativa honey and Seder honey. Manuka honey UMF +20 showed a bacteriocidal activity on both Imipenem resistant and sensitive P. aeruginosa, while Seder honey and N. sativa honey exerted only a bacteriostatic effect. Manuka honey UMF +10 showed most effect on antimicrobial resistance. Manuka honey UMF +10 had an effect on modulation of Imipenem resistant P. aeruginosa. CONCLUSION: The results indicated that various types of honey affected the test organisms differently. Modulation of antimicrobial resistance was seen in the case Manuka honey UMF +10.

The influence of Imipenem resistant metallo-beta-lactamase positive and negative Pseudomonas aeruginosa nosocomial infections on mortality and morbidity.

BACKGROUND: Metallo-beta-lactamase (MBL) mediated resistance to carbapenems is an emerging threat in Pseudomonas aeruginosa (PA) nosocomial infections. Limited data on role of Imipenem resistant MBL positive PA (IR-MBLP-PA) and IR-MBL negative-PA (IR-MBLN-PA) infections on mortality and morbidity initiated the present study. OBJECTIVES: The aim of this study is to determine the role of IR-MBLP-PA and IR-MBLN-PA infections on mortality and morbidity. MATERIALS AND METHODS: Prospective observational study of 1 year with 110 PA nosocomial infections was conducted with Imipenem + ethylene-diamine-tetra-acetic acid combined disc test for MBL detection. Role of IR-MBLP-PA and IR-MBLN-PA infections on the outcome and morbidity were assessed in terms of crude mortality rate, Charlson's comorbidity score and mean duration of stay in intensive care unit (ICU) until cure and until death, number of episodes of complications and underlying disease. Results were analyzed by z test for proportions and Student t-test. RESULTS: Relatively high crude mortality was observed among IR-MBLP-PA infections than IR-MBLN-PA (42.86% [6/14] vs. 20% [2/10], Z = 0.69, P = 0.49 NS). Ventilator-associated pneumonia was the underlying disease and a confounding factor in all deaths due to IR-MBLP-PA infections. IR-MBLP-PA infections resulted in rapid downhill course to death with short mean duration of stay in ICU until death than IR-MBLN-PA infections (3.167 ± 0.98 days vs. 16 ± 2.82, P < 0.001 highly significant [HS]) with more number of complications (5.85 ± 1.65 vs. 3.7 ± 1.31, P < 0.001 HS). With the exception of previous Imipenem therapy, association of higher Charlson's comorbidity score, severe underlying diseases, multidrug and pandrug resistance and pre-disposing risk factors with IR-MBLP-PA infections was not statistically significant. CONCLUSIONS: Higher mortality in IR-MBLP-PA than in IR-MBLN-PA was not significant indicating IR as an important predictor of mortality than MBL production. Higher morbidity and increased virulence was observed with certainty in IR-MBLP-PA infections.

Role of Imipenem-resistant metallo-beta-lactamase positive pseudomonas aeruginosa carriers in nosocomial infections.

BACKGROUND: Imipenem-resistant metallo-beta-lactamase Positive Pseudomonas aeruginosa (IR-MBLP-PA) infections occur as outbreaks and epidemics with a potential to spread within and between hospitals and intercontinentally. Limited data is available on IR-MBLP-PA carriers and their role as source and/or reservoir of nosocomial infection. OBJECTIVES: Detection and antibiogram typing of IR-MBLP-PA from healthy healthcare workers (HCW) from different areas of hospital and to assess role of carriers as source and/or reservoir of nosocomial infections. MATERIAL AND METHODS: Specimens from 200 HCWs [ICUs (120), General wards (40) and OPDs (40)] were collected from axilla, hands, stool and throat and processed by standard laboratory procedures. IR-MBLP-PA detection is done by IMIPENEM+EDTA combined disc test. Antibiogram typing is done. Association of carriers with clinical cases is done by IR-MBLP-PA with identical antibiogram type from carriers and cases. Distribution of carriers was assessed by Chi-square test. RESULTS: Incidence of P. aeruginosa and IR-MBLP-PA carriers among HCWs was 25%, 3.21% in ICUs, 10% from general wards and 0% from OPDs. A total of five IR-MBLP-PA antibiogram types were observed from four carriers and none from general wards and OPDs. Distribution of P. aeruginosa and IR-MBLP-PA carriers in different areas of hospital was not statistically significant with P values of 0.058 and 0.76, respectively. CONCLUSIONS: Role of IR-MBLP-PA carriers as source and/or reservoirs of infections could not be assessed with certainty; however, the possibility cannot be ruled out. Periodic carrier studies in targeted high risk areas of hospital should be undertaken.

Outbreaks of imipenem resistant Acinetobacter baumannii producing OXA-23 beta-lactamase in a tertiary care hospital in Korea.

PURPOSE: Since November 2006, imipenem-resistant Acinetobacter baumannii isolates have increased in Kyung Hee University Hospital in Seoul, Korea. The purpose of this study was to determine the genetic basis and molecular epidemiology of outbreak isolates. MATERIALS AND METHODS: Forty-nine non-repetitive isolates of the 734 IRAB strains were investigated in order to determine their characteristics. The modified Hodge and the ethylenediaminetetraacetic acid (EDTA)-disk synergy test were performed for the screening of carbapenemase and metallo-beta-lactamase production. Multiplex polymerase chain reaction (PCR) assays were performed for the detection of genes encoding for OXA-23-like, OXA-24-like, OXA-58-like and OXA-51-like carbapenemase. Pulsed-field gel electrophoresis (PFGE) was performed for strain identification. RESULTS: All isolates showed 100% resistance to ciprofloxacin and gentamicin, 97.9% resistance to cefepime, piperacillin/tazobactam, aztreonam, ceftazidime and piperacillin, 93.9% resistance to tobramycin and 57.1% resistance to amikacin. All of the 49 isolates (100%) showed positive results in the modified Hodge test and negative results in the EDTA-disk synergy test. They all (100%) possessed the encoding gene for an intrinsic OXA-51-like carbapenemase and an acquired OXA-23-like carbapenemase in the multiplex PCR assay. PFGE patterns revealed that all isolates were clonally related from A1 to A14. CONCLUSION: It is concluded that all of the 49 IRAB isolates acquired resistance to imipenem by producing OXA-23 carbapenemase and they might have originated from a common source.