Carbapenem-susceptible A. Baumannii Research Articles

Identifying risk factors for carbapenem-resistant Acinetobacter baumannii carriage upon admission: a case-case control study

BackgroundActive screening programs and early detection of asymptomatic carriers are effective in preventing carbapenem-resistant Acinetobacter baumannii (CRAB) dissemination in healthcare facilities. This study aims to identify risk factors associated with CRAB carriage among patients upon admission to an acute care hospital.MethodsA case-case-control study was conducted at an acute care hospital. Starting in June 2020, new admissions to medical wards underwent rectal and buccal screening. Patients with CRAB or carbapenem-susceptible A. baumannii (CSAB) carriage were compared to controls, randomly selected from patients with negative cultures, at a one-to-one ratio. Multinomial logistic regression using a backward stepwise method was employed to identify factors associated with CRAB and CSAB carriage. A Chi-square Automatic Interaction Detector analysis was also conducted to further elucidate risk factors.ResultsThe study included 115 CRAB carriers, 117 CSAB carriers and 121 controls. Increasing age was associated with a reduced risk of CSAB (OR: 0.96, p < 0.001) and CRAB carriage (OR: 0.97, p = 0.02), while higher Charlson Comorbidity Index scores increased the risk for both. CRAB carriage was significantly associated with admission from long-term acute care hospitals (OR: 7.68, p < 0.001) and presence of pressure ulcers (OR: 89.98, p < 0.001). Decision tree analysis identified pressure ulcers, prior location, and Charlson score as key predictors, with CRAB carriage reaching 77.3% in patients admitted from long-term acute care hospitals with pressure ulcers.ConclusionPressure ulcers were strongly associated with the carriage of both susceptible and resistant strains of A. baumannii. CRAB carriage was predominantly observed in patients transferred from long-term acute care hospitals, highlighting the need for targeted screening in this high-risk population.

Clinical and microbiological features of a cohort of patients with Acinetobacter baumannii bloodstream infections

PurposeAcinetobacter baumannii is emerging as a pathogen that is a focus of global concern due to the frequent occurrence of the strains those are extensively resistant to antibiotics. This study was aimed to analyze the clinical and microbiological characteristics of a cohort of patients with A. baumannii bloodstream infections (BSIs) in western China.MethodsA retrospective study of the patients at West China Hospital of Sichuan University with A. baumannii BSIs between Jan, 2018 and May, 2023 was conducted. Antimicrobial susceptibility of A. baumannii isolates was tested by microdilution broth method. Whole-genome sequencing and genetic analysis were also performed for these isolates.ResultsAmong the 117 patients included, longer intensive care unit stay, higher mortality, and more frequent invasive procedures and use of more than 3 classes of antibiotics were observed among the carbapenem-resistant A. baumannii (CRAB)-infected group (n = 76), compared to the carbapenem-susceptible A. baumannii (CSAB)-infected group (n = 41, all P ≤ 0.001). Twenty-four sequence types (STs) were determined for the 117 isolates, and 98.7% (75/76) of CRAB were identified as ST2. Compared to non-ST2 isolates, ST2 isolates exhibited higher antibiotic resistance, and carried more resistance and virulence genes (P < 0.05). In addition, 80 (68.4%) isolates were CRISPR-positive, showed higher antibiotic susceptibility, and harbored less resistance and virulence genes, in comparison to CRISPR-negative ones (P < 0.05). Phylogenetic clustering based on coregenome SNPs indicated a sporadic occurrence of clonal transmission.ConclusionOur findings demonstrate a high frequency of ST2 among A. baumannii causing BSIs, and high antibiotic susceptibility of non-ST2 and CRISPR-positive isolates. It is necessary to strengthen the surveillance of this pathogen.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Evolutionary trends of carbapenem-resistant and susceptible Acinetobacter baumannii isolates in a major tertiary care setting from North India

Emergence of carbapenem-resistant A. baumannii (CRAB) is a global, ongoing healthcare concern. CRAB is among the topmost priority pathogens, with various studies focusing on its global population structure and resistant allelic profiles. However, carbapenem-susceptible A. baumannii (CSAB) isolates are often overlooked due to their sensitivity to beta-lactams, which can provide important insights into origin of CRAB lineages and isolates. In the present study, we report genomic investigation of CRAB and CSAB coexisting in Indian hospital setting. MLST based population structure and phylogenomics suggest they mainly follow distinct evolutionary routes forming two phylogroups. PG-I exclusively for a successful clone (ST2) of CRAB and PG-II comprises diversified CSAB isolates except PG3373, which is CRAB. Additionally, there are few CRAB isolates not belonging to PG-I and sharing clonal relationship with CSAB isolates indicating role of genome plasticity towards extensive drug resistance in the nosocomial environment. Further, genealogical analysis depicts prominent role of recombination in emergence and evolution of a major CRAB lineage. Further, CRAB isolates are enriched in resistomes as compared to CSAB isolates, which were encoded on the genomic island. Such comparative genomic insights will aid in our understanding and localized management of rapidly evolving pandrug resistant nosocomial pathogens.

Insights into the epidemiology, risk factors, and clinical outcomes of carbapenem-resistant Acinetobacter baumannii infections in critically ill children.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a leading cause of nosocomial infections with an increasing impact on critically ill patients, yet there is limited data on contributing factors. This study was aim to evaluate the prevalence and risk factors, and clinical outcomes of CRAB infections among critically ill children in a tertiary university teaching hospital in China. From January 2016 to December 2021, all children diagnosed with nosocomial Acinetobacter baumannii (A. baumannii) infections in the pediatric intensive care unit (PICU) were identified through the computerized microbiology laboratory databases. Among them, children suffering from CRAB infection were designated as a case group, while children with carbapenem susceptible A. baumannii (CSAB) infection were assigned to a control group. This retrospective case-control study was based on two groups of patients to determine potential clinical factors contributing to CRAB infection and death among critically ill children via univariate and multivariate analyses. During the 6-year study period, a total of 372 episodes of nosocomial A. baumannii infection in the PICU were eligible and included in the study. These isolates displayed moderate or high rates of resistance to all tested antimicrobials except colistin. The overall prevalence of CRAB and MDRAB (multidrug-resistant A. baumannii) was 78.0% and 80.9%, respectively. Several risk factors found to significantly increase CRAB infection included receiving invasive operation (OR = 9.412, p = 0.001), gastric intubation (OR = 2.478, p = 0.026), prior carbapenems exposure (OR = 2.543, p = 0.003), severe pneumonia (OR = 3.235, p = 0.001), and hemoglobin <110g/L (OR = 3.049, p = 0.005). Of 372 patients with CRAB infection, the mortality rate was 30.9% (115/372) and mortality did not differ between children with CRAB and CSAB infections. Septic shock (OR = 2.992, p = 0.001), AST > 46U/L (OR = 2.015, p = 0.005), bone marrow aspiration (OR = 2.704, p = 0.008), lymphocyte <20 % (OR = 1.992, p = 0.006) and age (OR = 1.094, p = 0.002) were independent risk factors for the death of A. baumanni infection. This study highlights considerable incidence rate and remarkable mortality of children with A. baumanni (especially CRAB) infections, and identifies age-specific risk factors for CRAB infection and mortality in critically ill children. These risk factors should be taken into account in pediatric hospitals in order to establish early intervention and rational treatment to improve clinical outcomes.

Excess mortality and long-term disability from healthcare-associated carbapenem-resistant Acinetobacter baumannii infections: A nationwide population-based matched cohort study.

Carbapenem resistance is perceived as a clinical challenge in the management of debilitated and immunocompromised patients who eventually will die from underlying diseases. We aimed to examine whether carbapenem resistance per se, rather than the underlying diseases, negatively affect outcomes, by comparing the excess mortality and morbidity from healthcare-associated infections (HAIs) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-susceptible A. baumannii (CSAB). This was a nationwide retrospective matched cohort study of hospitalized patients in 96 hospitals which participated in Taiwan Nosocomial Infection Surveillance (TNIS). A total of 2,213 patients with A. baumannii HAIs were individually matched to 4,426 patients without HAIs. Main outcomes were excess risks for one-year all-cause mortality and one-year new-onset chronic ventilator dependence or dialysis-dependent end-stage renal disease. Excess one-year mortality was 27.2% in CRAB patients, compared with their matched uninfected inpatients, as well as 15.4% in CSAB patients (also compared with their matched uninfected inpatients), resulting in an attributable mortality of 11.8% (P <0.001) associated with carbapenem resistance. The excess risk associated with carbapenem resistance for new-onset chronic ventilator dependence was 5.2% (P <0.001). Carbapenem resistance was also associated with an extra cost of $2,511 per case of A. baumannii HAIs (P <0.001). Carbapenem resistance is associated with a significant disease burden in terms of excess mortality, long-term ventilator dependence, and medical cost. Further studies on effects of antimicrobial stewardship programs in decreasing this burden are warranted.

Functional characterization and clinical implication of a novel epidemic carbapenem-resistant Acinetobacter baumannii genetic marker

ObjectivesThe aim of the study was to evaluate the distribution and function of contact-dependent growth inhibition (CDI) systems associated with carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. MethodsIsolates were examined by multilocus sequence typing (MLST) and polymerase chain reaction (PCR) for the presence of CDI genes in CRAB and carbapenem-susceptible A. baumannii (CSAB) from patients with invasive disease in a medical center in Taiwan. Inter-bacterial competition assays were performed to characterize the in vitro function of the CDI system. ResultsA total of 89 (61.0%) CSAB and 57 (39.0%) CRAB isolates were collected and examined. ST787 (20/57; 35.1%) was the predominant sequence type among CRAB, followed by ST455 (10/57; 17.5%). More than half the CRAB (56.1%, 32/57) belonged to CC455 and more than one third (38.6%, 22/57) to CC92. A novel CDI system, cdiTYTH1, was found in 87.7% (50/57) of the CRAB but in only 1.1% (1/89) of the CSAB isolates (P<0.00001). The cdiTYTH1 was also identified in 94.4% (17/18) of previously genome-sequenced CRAB isolates and only one CSAB isolate from Taiwan. Two other previously reported CDI (cdi19606-1 and cdi19606-2) were not found in these isolates, except both were found in one CSAB. All six CRAB without cdiTYTH1 showed growth inhibition by a CSAB carrying cdiTYTH1 in vitro. All clinical CRAB isolates belonging to the predominant CC455 carried the newly identified cdiTYTH1. ConclusionsThis CDI system was widespread in CRAB clinical isolates and appeared to be an epidemic genetic marker for CRAB in Taiwan. The cdiTYTH1 was functional in vitro in bacterial competition assay.

Multicenter Study of the Risk Factors and Outcomes of Bloodstream Infections Caused by Carbapenem-Non-Susceptible Acinetobacter baumannii in Indonesia.

The prevalence of bacteremia caused by carbapenem-non-susceptible Acinetobacter baumannii (CNSAB) continues to increase, and it is associated with a high mortality rate. Early recognition of infection and mortality determinants risk factors is necessary for adequate antibiotic administration. We aimed to determine the risk factors and outcomes of CNSAB bacteremia in Indonesia. A multicenter case-control study was conducted in three referral hospitals in Indonesia. Data were collected retrospectively from January 2019 to December 2021. Cases were defined as patients with bacteremia where CNSAB was isolated from the blood, while the controls were patients with bacteremia caused by carbapenem-susceptible A. baumannii (CSAB). Risk factors for bacteremia and mortality associated with CNSAB bacteremia were determined using univariates analysis (chi-squared and Student’s t-test or Mann–Whitney test) and multivariate logistic regression analysis. A total of 144 bacteremia patients were included, of whom 72 patients were for each case and control group. The final model of multivariate regression analysis revealed that bacteremia source from the lower respiratory tract (adjusted odds ratio (aOR): 3.24; 95% CI: 1.58–6.63, p = 0.001) and the use of central venous catheter (aOR: 2.56; 95% CI: 1.27–5.18; p = 0.009) were independent risk factors for CNSAB bacteremia. Charlson Comorbidity Index ≥ 4 (aOR: 28.56; 95% CI: 3.06–265.90, p = 0.003) and Pitt Bacteremia Score ≥ 4 (aOR: 6.44; 95% CI: 1.17–35.38; p = 0.032) were independent risk factors for mortality due to CNSAB bacteremia. Only high Pitt Bacteremia Score was an independent risk factor for mortality of CSAB bacteremia. In conclusion, we identified the risk factors for CNSAB-associated bacteremia and the risk factors for death, which are relevant for empiric therapy and infection control prevention, as well as prognosis evaluation of patients with bloodstream infections.

Comparative analysis of carbapenemases, RND family efflux pumps and biofilm formation potential among Acinetobacter baumannii strains with different carbapenem susceptibility

AimThis study has conducted a comparative analysis of common carbapenemases harboring, the expression of resistance-nodulation-cell division (RND) family efflux pumps, and biofilm formation potential associated with carbapenem resistance among Acinetobacter baumannii (A. baumannii) strains with different carbapenem susceptibility. Methods: A total of 90 isolates of A. baumannii from two tertiary hospitals of China were identified and grouped as carbapenem susceptible A. baumannii (CSAB) strains and carbapenem non-susceptible A. baumannii (CnSAB) strains based on the susceptibility to imipenem. Harboring of carbapenemase genes, relative expression of RND family efflux pumps and biofilm formation potential were compared between the two groups. Result: Among these strains, 12 (13.3 %) strains were divided into the CSAB group, and 78 (86.7 %) strains into the CnSAB group. Compared with CSAB strains, CnSAB strains increased distribution of blaOXA−23 (p < 0.001) and ISAba1/blaOXA−51−like (p = 0.034) carbapenemase genes, and a 6.1-fold relative expression of adeB (p = 0.002), while CSAB strains led to biofilm formation by 1.3-fold than CnSAB strains (p = 0.021).ConclusionsClinically, harboring more blaOXA−23−like and ISAba1/blaOXA−51−like complex genes and overproduction of adeABC are relevant with carbapenem resistance, while carbapenem susceptible strains might survive the stress of antibiotic through their ability of higher biofilm formation.

Clinical and Economic Burden of Carbapenem-Resistant Infection or Colonization Caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii: A Multicenter Study in China.

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 < 0.0001; $4605, p < 0.0001; $7277, p < 0.0001) and excess LOS (13.2 days, p < 0.0001; 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.

Role of plasmid carrying bla NDM in mediating antibiotic resistance among Acinetobacter baumannii clinical isolates from Egypt.

We investigated antibiotic resistance levels among blaNDM-positive (n = 9) and -negative (n = 65) A. baumannii clinical isolates collected in 2010 and 2015 from Alexandria Main University Hospital, Egypt using disc diffusion and minimum inhibitory concentration (MIC) determination. Plasmids from blaNDM-positive isolates were transformed into a carbapenem-susceptible A. baumannii (CS-AB) isolate to assess the role of plasmid transfer in mediating carbapenem resistance. Imipenem, meropenem, and ertapenem MIC90 values against blaNDM-positive isolates were 128, > 256, and 256 µg/mL, respectively. Plasmid isolation and polymerase chain reaction revealed that blaNDM was plasmid mediated. The plasmids were electroporated into the cells of a CS-AB isolate at an efficiency of 1.3 × 10–8 to 2.6 × 10–7, transforming them to blaNDM-positive carbapenem-resistant cells with an imipenem MIC increase of 256-fold. In addition to carbapenem resistance, the blaNDM-positive isolates also exhibited higher levels of cephalosporins, tetracycline, aminoglycosides, fluoroquinolones, and colistin resistance than the blaNDM-negative isolates. Acquisition of blaNDM-carrying plasmids dramatically increased imipenem resistance among A. baumannii isolates. Intriguingly, blaNDM-positive isolates also showed a high degree of resistance to antibiotics of different classes. The potential co-existence of different resistance determinants on A. baumannii plasmids and their possible transfer owing to the natural competence of the pathogen are especially alarming. More effective infection control and antibiotic stewardship programs are needed to curb the spread and treat such infections in both hospital and community settings.Electronic supplementary materialThe online version of this article (10.1007/s13205-020-2157-y) contains supplementary material, which is available to authorized users.

In vitro and In vivo Fitness of Clinical Isolates of Carbapenem-Resistant and -Susceptible Acinetobacter baumannii

AbstractContext:Acinetobacter baumannii is one among the leading nosocomial pathogens in the healthcare settings worldwide. Limited data on relative fitness and virulence of carbapenem-resistant A. baumannii (CRAB) are known. New methods are required to curb the rapidly rising antimicrobial resistance of this bug. Aims: We aimed to study the comparative in vitro and in vivo fitness of clinical isolates of CRAB and carbapenem-susceptible A. baumannii (CSAB). Settings and Design: A total of nine A. baumannii isolates were included in this study. CSAB ATCC-19606 was taken as a reference control strain. Subjects and Methods: Matrix-assisted laser desorption ionisation–time of flight mass spectrometry and gyrB and blaOXA-51 PCR were used for species identification. Antimicrobial susceptibility was performed using Kirby-Bauer disk-diffusion method. Minimum inhibitory concentration for carbapenems (imipenem, meropenem and doripenem) was determined using agar dilution method. End point analysis, competitive index (CI), growth kinetics and generation time were determined for CRAB and CSAB isolates. In vivo fitness of CRAB and CSAB was determined using Caenorhabditis elegans host model. Multilocus sequence typing was performed to see the genetic relatedness of the isolates under study. Results: End point analysis, in vitro CI and growth kinetics experiments showed better fitness of clinical isolates of CRAB over CSAB ones. In vivo ‘nematode fertility assay’ using C. elegans also supported the in vitro results. Conclusions: To the best of our knowledge, this is the first study of its kind from India showing difference in fitness of clinical isolates of CRAB and CSAB.

Corrigendum to "Determinants of Mortality in Patients with Nosocomial Acinetobacter baumannii Bacteremia in Southwest China: A Five-Year Case-Control Study".

[This corrects the article DOI: 10.1155/2018/3150965.].

High prevalence and clonal dissemination of OXA-72-producing Acinetobacter baumannii in a Chinese hospital: a cross sectional study

BackgroundCarbapenem resistance in Acinetobacter baumannii in China was mainly mediated by OXA-23-like carbapenemases, while OXA-24/40-like carbapenemases were rarely identified. OXA-72 is one variant of OXA-24/40-like carbapenemases. This study aimed to demonstrate the epidemiology and characterizations of OXA-72-producing A. baumannii in a Chinese hospital.MethodsA total of 107 clinical A. calcoaceticus-A. baumannii (Acb) complex isolates were collected in a Chinese hospital during between 2014 and 2016. These isolates were identified using Vitek 2 system and gyrB multiplex PCR. Vitek 2 system was used for antibiotic susceptibility testing. Genes encoding for major classes of carbapenemases were investigated by PCR. Rep-PCR was used for genotyping of all the A. baumannii isolates. The risk factors for carriage of OXA-72-producing or OXA-23-producing A. baumannii were analyzed through univariate and multivariate logistic regression.ResultsOf the 107 Acb isolates collected, 101 isolates (94.4%) and 6 isolates (5.6%) were identified as A. baumannii and A. pittii, respectively. 78 A. baumannii isolates (77.2%) were carbapenem resistant and mainly cultured from intensive care unit (ICU). blaOXA-72 and blaOXA-23 genes were identified in 45(57.7%) and 33(42.3%) carbapenem-resistant A. baumannii (CRAB), respectively. Multivariate risk factor analyses showed that prior carbapenem usage and nasogastric intubation were significantly associated with carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii. Rep-PCR analysis showed that 9 and 22 Rep-PCR types were assigned to 78 CRAB isolates and 23 carbapenem-susceptible A. baumannii (CSAB) isolates, respectively. A higher diverstiy of Rep-PCR patterns was observed among OXA-72-producing A. baumannii isolates than OXA-23-producing A. baumannii isolates, but all of them belonged to the same clone complex. MLST analysis suggested that the OXA-72 isolates from this study correspond to CC92/CC2 clone complex.ConclusionsThis study demonstrates high prevalence and potential clonal spread of closely related genotypes of OXA-72-producing A. baumannii within a Chinese hospital. Continuous surveillance is necessary to monitor the dissemination of these strains in other healthcare settings to guide infection control policies in order to curb the spread of this bacterium.

Determinants of Mortality in Patients with Nosocomial Acinetobacter baumannii Bacteremia in Southwest China: A Five-Year Case-Control Study.

Purpose This study was aimed to identify the determinants of in-hospital mortality in Acinetobacter baumannii (A. baumannii) bacteremia and to assess impact of carbapenem resistance on mortality. Methods A five-year case-control study was conducted from January 2011 to December 2015 in a tertiary teaching hospital with 3200 beds, Southwest China. Clinical outcomes and potential determinants of mortality in patients with nosocomial A. baumannii bacteremia and carbapenem-resistant A. baumannii (CRAB) bacteremia were evaluated using Cox and logistic regression analyses. Results A total of 118 patients with nosocomial A. baumannii bacteremia were included. Seventy-one percent (84/118) of them had carbapenem-resistant A. baumannii (CRAB) bacteremia. The in-hospital mortality of nosocomial A. baumannii bacteremia was 21.2%, and the attributable in-hospital mortality rate due to CRAB was 21.5%. Significant difference of 30-day in-hospital mortality in the Kaplan–Meier curves was found between CRAB and CSAB groups (log-rank test, P=0.025). The Cox regression analysis showed that patients with CRAB bacteremia had 2.72 times higher risk for 30-day in-hospital mortality than did those with carbapenem-susceptible A. baumannii (CSAB) bacteremia (95% confidence intervals (CIs) 1.14–6.61, P=0.016). The logistic regression analysis reported that mechanical ventilation and respiratory tract as origin of bacteremia were independent predictors of mortality among patients with nosocomial A. baumannii bacteremia and CRAB bacteremia, while high APACHE II score on the day of bacteremia and multiple organ dysfunction syndromes (MODS) during hospitalization were independent predictors of mortality among patients with nosocomial A. baumannii bacteremia but not CRAB bacteremia. Conclusion It was the severity of illness (high APACHE II score and MODS) not carbapenem resistance that highlighted the mortality of patients with nosocomial A. baumannii bacteremia. The impact of mechanical ventilation on mortality suggested that respiratory dysfunction might prime the poor outcome. Protection of respiratory function during the progression of nosocomial A. baumannii bacteremia should be given more importance. Early identification and intervention of patients with nosocomial A. baumannii bacteremia in critical ill conditions were advocated.

Carbapenem-resistant Acinetobacter baumannii (CRAB) Recovered from Burn Patients.

Emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) and their prolonged presence in burn units increases the risk of acquisition of CRAB.Methods. From November 2012 to September 2013, 1474 burn patients were screened for CRAB isolates through testing susceptibility to imipenem and its comparators meropenem, and doripenem. Furthermore, the in vitro activity of other antibiotics against CRAB was investigated. Results. Three patients were infected with carbapenem-susceptible A. baumannii (CSAB) and 168 were infected with CRAB. Approximately one-fifth (n=32) of CRAB isolates were obtained from patients hospitalized in Burn Intensive Care Unit (BICU). Most of CRABs were isolated from wound. The mean length of stay (LOS) in hospital prior to A. baumannii isolation was significantly higher for CRAB compared to CSAB cases (P=0.04). Amongst the independent variables, percentage of total burn surface area (TBSA) significantly increased the mortality rate using multivariate logistic regression (P=0.001, OR= 16.5; 95% CI: 4.72-57.7). The majority of tested isolates were resistant to imipenem (94.8%), and to its comparators, doripenem (97.7%), and meropenem (97.7%). The susceptibility of CRAB isolates was less than 10% to all tested antibiotics except for colistin (100%), doxycycline (61.9%), gentamicin (18.5%), and tigecycline (11.9%).Conclusion. Resistance to carbapenem reduces the number of effective antibiotics. The coordinated and intensive efforts of healthcare personnel are required to meet the challenge of dissemination of CRAB.

Carbapenem resistance and mortality in patients with Acinetobacter baumannii infection: systematic review and meta-analysis

Acinetobacter baumannii has emerged as a major cause of healthcare-associated infections. Controversy exists as to whether antimicrobial resistance increases the risk of mortality. We conducted a systematic review and meta-analysis to examine this association. We searched MEDLINE and EMBASE databases up to May 2013 to identify studies comparing mortality in patients with carbapenem-resistant A. baumannii (CRAB) vs. carbapenem-susceptible A. baumannii (CSAB). A random-effects model was used to pool Odds Ratios (OR). Heterogeneity was examined using I2. We included 16 observational studies. There were 850 reported deaths (33%) among the 2546 patients. Patients with CRAB had a significantly higher risk of mortality than patients with CSAB in the pooled analysis of crude effect estimates (crude OR = 2.22; 95% CI = 1.66, 2.98), although substantial heterogeneity was evident (heterogeneity I2 = 55%). The association remained significant in the pooled adjusted OR of 10 studies. Studies reported that patients with CRAB compared to patients with CSAB were more likely to have severe underlying illness and also to receive inappropriate empirical antimicrobial treatment, which increases the risk of mortality. Our study suggests that carbapenem resistance may increase the risk of mortality in patients with A. baumannii infection. However, cautious interpretation is required because of the residual confounding factors and inadequate sample size in most studies.

Risk factors and mortality of patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia

Acinetobacter baumannii is characterized by strictly aerobic, gram-negative, nonmotile, nonlactose-fermenting, oxidase-negative, catalase-positive coccobacilli, and the combination of its environmental resilience and its rapid development of resistance to multiple classes of antimicrobials renders it a successful nosocomial pathogen. The aim of this study was to identify specific risk factors and outcome of nosocomial pneumonia because of carbapenem-resistant Acinetobacter baumannii (CRAB). The retrospective study, set in a 1,500-bed referral and tertiary care hospital, was conducted to analyze the clinical and microbiologic data of patients with nosocomial pneumonia because of Acinetobacter baumannii (A baumannii) from January 2006 to December 2011. Comparisons were made between patients with CRAB pneumonia and patients with carbapenem-susceptible A baumannii (CSAB) pneumonia. Only the first isolation of A baumannii was considered. A total of 145 patients with CSAB pneumonia and 97 patients with CRAB pneumonia was included. Among these patients, the independent risk factors for acquiring CRAB pneumonia were Acute Physiology and Chronic Health Evaluation II (APACHE II) score (>20) at admission, systemic illnesses (chronic respiratory disease and cerebrovascular accident), presence of excess noninvasive or invasive devices (mechanical ventilation), and ever used antibiotics within 28 days (carbapenem and cefepime). The patients with CRAB pneumonia had higher mortality rate than CSAB pneumonia. Multivariate analysis showed that, among patients with A baumannii pneumonia, APACHE II score (>20) at pneumonia onset, infections with other microorganisms, and inappropriate therapy were independently associated with 28-day mortality. Patients with CRAB pneumonia have a higher mortality rate than those with CSAB pneumonia. The nosocomial occurrence of CRAB pneumonia is strongly related to systemic illnesses, APACHE II score, mechanical ventilation, and ever used antibiotics within 28 days.

Clonal Spread of Carbapenem Non-susceptible Acinetobacter baumannii in an Intensive Care Unit in a Teaching Hospital in China

BackgroundThis study was aimed to investigate the genetic diversity and antibiotic resistance profile of the nosocomial infection agent Acinetobacter baumannii from a medical intensive care unit (ICU) in a teaching hospital in Suzhou, China.MethodsThe genetic relationship among A. baumannii isolates in an ICU was investigated using multilocus sequence typing (MLST). The antibiotic resistance pattern was determined by performing an antibiotic susceptible test, which included an agar dilution method and an E-test method. Resistant determinants, e.g., carbapenemase genes, metallo-β-lactamases, and class 1 integron, were analyzed by specific PCR and DNA sequencing.ResultsIn the present study, 33 non-duplicate isolates were identified as 5 existing sequence types (STs) (ST92, ST75, ST112, ST145, and ST345) and 1 new sequence type STn, which has a G-A mutation at nt268 on ropD40 of ST251. These results reveal limited diversity in carbapenem non-susceptible A. baumannii (CNSAb) isolates in our ICU, which are comprised of only 2 distinct STs, with ST92 and ST75 clustering into a clonal complex (CC) 92. Most CNSAb isolates (94.4%, 17/18) harbored the OXA-23 gene, while no carbapenem-susceptible A. baumannii (CSAb) isolates harbored it. In addition, 66.7% (22/33) isolates were positive for class 1 integrase, and gene cassette analysis showed there are 3 gene arrays among them, i.e., aacA4-catB8-aadA1 (77.3%, 17/22), aacA4 (22.7%, 5/22), and aacC1-orfX-orfX'-aadA1 (4.5%, 1/22).ConclusionsWhen all these data are combined, the antibiotic resistance and wide distribution of CNSAb isolates in our ICU are probably caused by expansion of the CC92 clone.

Risk factors and clinical outcomes of patients with carbapenem-resistant Acinetobacter baumannii bacteremia

It is still controversial whether carbapenem-resistant Acinetobacter baumannii (CRAB) is an independent risk factor for mortality. This study aimed to determine the risk factors and outcomes of patients with CRAB bacteremia, compared to those with carbapenem-susceptible A. baumannii (CSAB) bacteremia. This retrospective cohort study was conducted in Taipei Veterans General Hospital, Taiwan. Patients with bacteremia due to A. baumannii during June 2002 and December 2007 were included. A total of 62 patients with CRAB and 164 with CSAB bacteremia were included. Among these patients, the independent risk factors for acquiring CRAB bacteremia were hematological malignancy [odds ratio (OR): 4.04; 95% confidence interval (CI): 1.29-12.70; p=0.017], previous use of cefepime (OR: 2.60; 95% CI 1.11-6.08; p=0.028) and use of totalparenteral nutrition (OR: 3.06; 95% CI 1.12-8.39; p=0.029). The patients with CRAB bacteremia had higher mortality rate than those with CSAB bacteremia. However, multivariate analysis showed that among patients with A. baumannii bacteremia, acquisition of CRAB by itself was not an independent risk factor for 14-day mortality. Instead, the independent factors predicting14-day mortality were Acute Physiology and Chronic Health Evaluation (APACHE) score>20 (OR: 6.33; 95% CI: 2.32-17.26; p<0.001), shock (OR: 2.68; 95% CI: 1.11-6.23; p=0.025) and inappropriate antimicrobial therapy (OR: 2.14; 95% CI: 1.01-4.53; p=0.046). Risk factors for CRAB bacteremia were hematological malignancies, previous use of cefepime and use of total parenteral nutrition. Acquisition of CRAB itself is not a poor prognostic factor for the patients with A. baumannii bacteremia.