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Background: There are multiple antibiotic regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) in clinical practice. We conducted this meta-analysis to compare the efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections., Methods: Two authors independently searched the PubMed, Web of Science, Embase, and Cochrane databases from their establishment to April 15, 2024, to search for randomized controlled trials (RCTs) or cohort studies, and compared the clinical efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. The Newcastle Ottawa Scale (NOS) checklist was used to evaluate the quality of the included studies. The primary outcome was all-cause mortality, and subgroup analysis was conducted on the basis of the site of infection and the risk of bias in the studies. Trial sequential analysis (TSA) was then conducted., Results: Six observational studies were included, with 251 cases in the cefiderocol-based group and 372 cases in the colistin-based group. Compared to the colistin-based group, the cefiderocol-based group had lower all-cause mortality (RR = 0.71, 95% CI: 0.54-0.92, P = 0.01) and 30-day mortality (RR = 0.64, 95% CI: 0.43-0.95, P = 0.03). However, for the 14-day and 28-day mortality rates, there was no statistically significant difference between two groups. According to the subgroup analysis, among patients with bloodstream infection (BSI), the cefiderocol-based group had lower all-cause mortality, but it did not reduce the mortality of ventilator-associated pneumonia (VAP) patients. The result of TSA showed that our conclusions are reliable. There was no significant statistical difference in the microbiological cure rate, clinical cure rate, or duration of hospitalization. In addition, the cefiderocol-based group did not have an increased incidence of acute kidney injury (AKI)., Conclusions: Compared with the colistin-based regimens, the cefiderocol-based regimens were significantly associated with a lower risk of mortality in CRAB-infected patients, especially for patients with BSI. However, they did not show any advantages in terms of the clinical cure rate or microbiological cure rate, nor did they reduce the incidence of AKI., Prospero Registration Number: CRD42023487213., (© 2024. The Author(s).)

Objectives: This study analyzed the risk and impact of developing pneumogenic bacteremia in patients with CRAB nosocomial pneumonia in ICU., Methods: This is multicenter retrospective study. Clinical outcomes were compared between bacteremia and non-bacteremia group, and the risk factors for mortality and developing pneumogenic CRAB bacteremia were analyzed., Results: After patient recruitment, 164 cases were in the bacteremia group, and 519 cases were in the non-bacteremia group. The bacteremia group had 22.4 percentage of increase in-hospital mortality than the non-bacteremia group (68.3% vs 45.9%, P < 0.001). Multivariate analysis showed bacteremia was an independent risk factor for in-hospital mortality (aHR = 2.399, P < 0.001). A long time-interval between ICU admission and pneumonia onset was an independent risk factor for developing bacteremia (aOR = 1.040, P = < 0.001). Spearman's rank correlation analysis indicated a high correlation between the days from ICU admission to pneumonia onset and the days of ventilator use before pneumonia onset (correlation coefficient (ρ) = 0.777)., Conclusions: In patients with CRAB nosocomial pneumonia, bacteremia increased the in-hospital mortality, and a longer interval from ICU admission to pneumonia onset was an independent risk factor for developing bacteremia, which was highly associated with the use of mechanical ventilation., Competing Interests: Declarations of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Acinetobacter baumannii (A. baumannii) nosocomial infections represent a serious hazard to public health, given high mortality rates and rapid spread of multidrug-resistance. The primary outcome of this study was to evaluate predictors of 14- and 30-d mortality in bloodstream infections (BSIs) due to both carbapenem-resistant and carbapenem-sensitive Acinetobacter. Secondary end points were to identify risk factors for BSIs due to carbapenem-resistant A. baumannii (CRAB) and to develop a predictive model for mortality in CRAB-related BSIs., Methods: Between 2019 and 2023, all consecutive hospitalized adult patients with bacteraemia due to A. baumannii were retrospectively enrolled at a single-centre., Results: One hundred twenty-six episodes of BSI caused by A. baumannii were recorded, 89.7% of which were due to CRAB. Recent burn injuries, older age, previous CRAB colonization, and antibiotics exposure were identified as risk factors for acquiring CRAB BSI. Overall, 14-d mortality was observed in 26.1% of the patients and 30-d mortality in 30.9% of the patients. On multivariate analysis, the Sequential Organ Failure Assessment (SOFA) score was associated with both 14- and 30-d mortality, whereas burn injuries correlated with 30-d survival. Concurrent coronavirus disease (COVID) was associated with mortality, although not reaching statistical figures. No major impact of receiving appropriate treatment was observed. Based on these findings, a multivariable model to predict mortality among patients with CRAB BSI was built and internally validated., Conclusions: A. baumannii BSIs are characterized by poor outcomes and limited therapeutic options. This study aimed to assist physicians in prompt identification of patients who are at greater risk of death, contributing to more informed clinical decision making., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections., Methods: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model., Results: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success., Conclusions: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

We compared clinical outcomes of patients who received monotherapy and combination therapy for treatment of MDR A. baumannii VAP. 170 patients were included. Vasopressor use and mortality rate were higher for combination therapy (69.3% versus 28.6%, p=0.024; 67.5% versus 14.3%, p=0.007; respectively). Majority received polymyxin B-based combination therapy, with higher mortality than those without polymyxin B (80.2% versus 19.8%, p=0.043). After adjusting for vasopressor use, monotherapy, dual combination, and triple combination therapy were not associated with mortality (aHR 0.24, 95% CI 0.03 to 1.79, p=0.169; aHR 1.26, 95% CI 0.79 to 2.00, p=0.367; aHR 0.93, 95% CI 0.57 to 1.49, p=0.744; respectively). There was no difference in adverse effects and length of stay between the two groups. Mortality from MDR A. baumannii VAP was high and not associated with monotherapy or combination therapy after adjustment for vasopressor use. Antibiotic regimens other than those containing polymyxin are urgently needed for the treatment of these infections., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia., (© 2024. The Author(s).)

Background: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI)., Materials/methods: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW)., Results: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival., Conclusions: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided., (© 2024. The Author(s).)

Purpose: Acinetobacter baumannii (Ab) is a Gram-negative opportunistic bacterium responsible for nosocomial infections or colonizations. It is considered one of the most alarming pathogens due to its multi-drug resistance and due to its mortality rate, ranging from 34 to 44,5% of hospitalized patients. The aim of the work is to create a predictive mortality model for hospitalized patient with Ab infection or colonization., Methods: A cohort of 140 sequentially hospitalized patients were randomized into a training cohort (TC) (100 patients) and a validation cohort (VC) (40 patients). Statistical bivariate analysis was performed to identify variables discriminating surviving patients from deceased ones in the TC, considering both admission time (T0) and infection detection time (T1) parameters. A custom logistic regression model was created and compared with models obtained from the "status" variable alone (Ab colonization/infection), SAPS II, and APACHE II scores. ROC curves were built to identify the best cut-off for each model., Results: Ab infection status, use of penicillin within 90 days prior to ward admission, acidosis, Glasgow Coma Scale, blood pressure, hemoglobin and use of NIV entered the logistic regression model. Our model was confirmed to have a better sensitivity (63%), specificity (85%) and accuracy (80%) than the other models., Conclusion: Our predictive mortality model demonstrated to be a reliable and feasible model to predict mortality in Ab infected/colonized hospitalized patients., (© 2024. The Author(s).)

Background: Patients infected with Acinetobacter baumannii (AB) bacteremia in hospital have high morbidity and mortality. We analyzed the clinical characteristics of pneumonia and nonpneumonia-related AB bloodstream infections (AB BSIs) and explored the possible independent risk factors for the incidence and prognosis of pneumonia-related AB BSIs., Methods: A retrospective monocentric observational study was performed. All 117 episodes of hospital-acquired AB bacteremia sorted into groups of pneumonia-related AB BSIs (n = 45) and nonpneumonia-related AB BSIs (n = 72) were eligible. Univariate/multivariate logistic regression analysis was used to explore the independent risk factors. The primary outcome was the antibiotic susceptibility in vitro of pneumonia-related AB BSIs group. The secondary outcome was the independent risk factor for the pneumonia-related AB BSIs group., Results: Among 117 patients with AB BSIs, the pneumonia-related group had a greater risk of multidrug resistant A. baumannii (MDRAB) infection (84.44%) and carbapenem-resistant A. baumannii (CRAB) infection (80%). Polymyxin, minocycline and amikacin had relatively high susceptibility rates (> 80%) in the nonpneumonia-related group. However, in the pneumonia-related group, only polymyxin had a drug susceptibility rate of over 80%. Univariate analysis showed that survival time (day), CRAB, MDRAB, length of hospital stay prior to culture, length of ICU stay prior to culture, immunocompromised status, antibiotics used prior to culture (n > = 3 types), endotracheal tube, fiberoptic bronchoscopy, PITT, SOFA and invasive interventions (n > = 3 types) were associated with pneumonia-related AB bacteremia. The multivariate logistic regression analysis revealed that recent surgery (within 1 mo) [P = 0.043; 0.306 (0.098-0.962)] and invasive interventions (n > = 3 types) [P = 0.021; 0.072 (0.008-0.671)] were independent risk factors related to pneumonia-related AB bacteremia. Multivariate logistic regression analysis revealed that length of ICU stay prior to culture [P = 0.009; 0.959 (0.930-0.990)] and recent surgery (within 1 mo) [P = 0.004; 0.260 (0.105-0.646)] were independent risk factors for mortality in patients with pneumonia-related AB bacteremia. The Kaplan‒Meier curve and the timing test showed that patients with pneumonia-related AB bacteremia had shorter survival time compared to those with nonpneumonia-related AB bacteremia., Conclusions: Our study found that A. baumannii had a high rate of antibiotic resistance in vitro in the pneumonia-related bacteremia group, and was only sensitive to polymyxin. Recent surgery was a significantly independent predictor in patients with pneumonia-related AB bacteremia., (© 2024. The Author(s).)

Background: The best treatment for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is still a matter of debate., Objectives: To describe the outcomes of patients treated with cefiderocol for CRAB infections, and to compare the efficacy of cefiderocol versus best available therapy (BAT)., Data Sources: We searched MEDLINE, the Cochrane Library and EMBASE to screen original reports published up to September 2023., Study Eligibility Criteria: Randomized controlled trials (RCTs) and observational studies investigating 30-day mortality, clinical failure, microbiological failure or rate of adverse drug reactions of patients treated with cefiderocol or BAT., Participants: Patients with infections due to CRAB., Interventions: Cefiderocol in monotherapy or in combination with other potentially active agents or BAT., Assessment of Risk of Bias: We used the Cochrane Risk of Bias Tool for RCTs, and the Newcastle Ottawa scale for observational studies., Methods of Data Synthesis: We conducted a meta-analysis pooling risk ratios (RRs) through random effect models., Results: We screened 801 original reports, and 18 studies (2 RCTs, 13 cohort studies and 3 case-series) were included in the analysis, for a total 733 patients treated with cefiderocol, and 473 receiving the BAT. Among patients receiving cefiderocol, the 30-day mortality rate was 42% (95% CI 38-47%), the rate of microbiological failure 48% (95% CI 31-65%), the clinical failure rate 43% (95% CI 32-55%), and the rate of ADRs was 3% (95% CI 1-6%). A lower mortality rate was observed among patients receiving cefiderocol monotherapy as compared to those treated with combination regimens (RR: 0.64; 95% CI: 0.43-0.94, p = 0.024). We found a significantly lower mortality rate (RR: 0.74; 95% CI: 0.57-0.95, p = 0.02) and a lower rate of ADRs (RR: 0.28; 95% CI: 0.09-0.91, p = 0.03) in the group treated with cefiderocol as compared to BAT. No difference was observed in microbiological and clinical failure rate., Conclusions: Our data strengthen the efficacy and safety profile of cefiderocol in CRAB infections., Competing Interests: Declaration of Competing Interest All the authors declare that they have no conflict of interest with the present paper, Cefiderocol either in monotherapy or combination versus best available therapy in the treatment of carbapenem-resistant Acinetobacter baumannii infections: a systematic review and meta-analysis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To perform a systematic review with meta-analysis to assess the clinical efficacy of cefiderocol-based regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections., Methods: Two authors independently searched PubMed-MEDLINE, Scopus, and Cochrane databases, from inception to 02 July 2023, for randomised controlled trials (RCTs) or observational studies comparing clinical efficacy of cefiderocol-based vs. non-cefiderocol-based regimens in patients with CRAB infections. Data were extracted by the two authors independently, and the quality of included studies was independently assessed using ROB 2.0 or ROBINS-I tools. Primary outcome was mortality rate. Meta-analysis was performed by pooling odds ratios (ORs) retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity., Results: A total of 530 articles were screened, and 6 studies (1 RCT and 5 observational; N=561; 247 cefiderocol-based vs. 314 non-cefiderocol-based regimens) were included. Cefiderocol did not significantly reduce in-hospital mortality compared to alternative therapies (predominantly colistin-based), but the confidence intervals around the effect estimate included clinically important benefit (N=5; OR 0.64; 95%CI 0.40-1.04; I 2 =57.5%). When only observational studies providing adjustment for confounders were considered, a lower risk of mortality was found in patients treated with cefiderocol-based regimens (N=4; OR 0.53; 95%CI 0.39-0.71; I 2 =0.0%)., Conclusions: Cefiderocol-based regimens were associated with a significantly lower risk of mortality in patients with CRAB infections in observational studies providing proper adjustment for confounders., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo . Capsule locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn't. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer ( P  < 0.001), a higher percentage had pneumonia ( P  = 0.004), and the white blood cell count was lower ( P  = 0.03). Infection with KL2 A. baumannii predicted mortality (adjusted hazard ratio [aHR], 2.03; 95% confidence interval [CI], 1.09-3.78; P  = 0.03), independently of the Pitt bacteraemia score (aHR, 1.34; 95% CI, 1.23-1.46; P  < 0.001) and leucopenia (aHR, 2.16; 95% CI, 1.30-3.57; P  = 0.003). Thrombocytopenia contributed to the effect of KL2 on mortality in bacteraemia (Sobel test P  = 0.01). Large-scale studies are warranted to confirm these findings and the underlying mechanisms deserve further investigation.

Delays in treating bacteremias with antibiotics to which the causative organism is susceptible are expected to adversely affect patient outcomes. Quantifying the impact of such delays to concordant treatment is important for decision-making about interventions to reduce the delays and for quantifying the burden of disease due to antimicrobial resistance. There are, however, potentially important biases to be addressed, including immortal time bias. We aimed to estimate the impact of delays in appropriate antibiotic treatment of patients with Acinetobacter species hospital-acquired bacteremia in Thailand on 30-day mortality by emulating a target trial using retrospective cohort data from Sunpasitthiprasong Hospital in 2003-2015. For each day, we defined treatment as concordant if the isolated organism was susceptible to at least 1 antibiotic given. Among 1,203 patients with Acinetobacter species hospital-acquired bacteremia, 682 had 1 or more days of delays to concordant treatment. Surprisingly, crude 30-day mortality was lower in patients with delays of ≥3 days compared with those who had 1-2 days of delays. Accounting for confounders and immortal time bias resolved this paradox. Emulating a target trial, we found that these delays were associated with an absolute increase in expected 30-day mortality of 6.6% (95% confidence interval: 0.2, 13.0), from 33.8% to 40.4%., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Nosocomial infections caused by Acinetobacter baumannii (A. baumannii) nosocomial infections caused by Acinetobacter baumannii (A. baumannii) are considered as a global serious problem in hospitalized patients because of emerging antibiotic resistance. Immunotherapy approaches are promising to prevent such infections. In our previous study, five antigenic epitopes of outer membrane protein A (OmpA), as the most dangerous virulence molecule in A. baumanii, were predicted in silico. In this study, the investigators evaluated some immunological aspects of the peptides. Five peptides were separately injected into C5BL/6 mice; then the cytokine production (interleukin-4 and interferon-gamma) of splenocytes and opsonophagocytic activity of immunized serum were assessed. To identify the protective function of the peptides, animal models of sepsis and pneumonia infections were actively and passively immunized with selected peptides and pooled sera of immunized mice, respectively. Then, survival rates of them were compared with the non-infected controls. Based on the results, activated spleen cells in P127 peptide-immunized mice exhibited an increase level of IFN-γ compared with the other experimental groups, but not about the IL-4 concentration. The results of opsonophagocytic assay revealed an appropriate killing activity of produced antibodies against A. baumannii in a dose-dependent manner. Further, the survival rates of the mice under passive immunization with the immunized sera or active immunization with P127 peptide were significantly more than those in the control group. Moreover, the survival rate of the P127 peptide immunized group was considerably higher than that among the other peptide-immunized group. In conclusion, findings indicated that peptides derived from outer membrane protein-A can be used as a promising tool for designing the epitope-based vaccines against infections caused by A. baumannii.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii , causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay ( p  = 0.002), steroid therapy ( p  = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p  < 0.001). Low-dose aspirin intake was associated with both MDR infection ( p  = 0.043) and survival ( p  = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use ( p  = 0.035) and an earlier onset of MDR infection ( p  = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Data on the relationship between antimicrobial resistance and mortality remain scarce, and this relationship needs to be investigated in intensive care units (ICUs). The aim of this study was to compare the ICU mortality rates between patients with ICU-acquired pneumonia due to highly antimicrobial-resistant (HAMR) bacteria and those with ICU-acquired pneumonia due to non-HAMR bacteria. We conducted a multicenter, retrospective cohort study using the French National Surveillance Network for Healthcare Associated Infection in ICUs ("REA-Raisin") database, gathering data from 200 ICUs from January 2007 to December 2016. We assessed all adult patients who were hospitalized for at least 48 h and presented with ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii. The association between pneumonia caused by HAMR bacteria and ICU mortality was analyzed using the whole sample and using a 1:2 matched sample. Among the 18,497 patients with at least one documented case of ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii, 3081 (16.4%) had HAMR bacteria. The HAMR group was associated with increased ICU mortality (40.3% vs. 30%, odds ratio (OR) 95%, CI 1.57 [1.45-1.70], P < 0.001). This association was confirmed in the matched sample (3006 HAMR and 5640 non-HAMR, OR 95%, CI 1.39 [1.27-1.52], P < 0.001) and after adjusting for confounding factors (OR ranged from 1.34 to 1.39, all P < 0.001). Our findings suggest that ICU-acquired pneumonia due to HAMR bacteria is associated with an increased ICU mortality rate, ICU length of stay, and mechanical ventilation duration., (© 2021. The Author(s).)

Colistin is an, antibiotic used to treat carbapenem-resistant Acinetobacter baumannii complex (CRABC) infection. However, colistin is well known for its nephrotoxicity. To accurately assess the effects of colistin on acute kidney injury (AKI) and 28-day mortality, we investigated the risk factors associated with AKI and mortality in patients with CRABC bacteremia who received or never received colistin. Patients with CRABC bacteremia aged ≥18 years were retrospectively identified for 3 years at five tertiary teaching hospitals. AKI was defined by using the Kidney Disease Improving Global Outcomes criteria. AKI developed in 103 (34.9%) of the 295 patients enrolled patients. AKI developed more frequently in patients who received colistin than in patients who did not (46.7% vs. 29.5%, p  = 0.004). Multivariate analysis showed that intravenous colistin usage was an independent risk factor for AKI in these patients. Nonfatal disease, catheter-related bloodstream infection, and administration of colistin were protective factors for 28-day mortality. However, the sequential organ failure assessment score and AKI were associated with poor outcomes. In conclusion, colistin may be a double-edged sword; although it causes AKI, it also reduces 28-day mortality in patients with CRABC bacteremia. Therefore, colistin administration as an appropriate antibiotic may improve CRABC bacteremia prognosis, despite its nephrotoxicity.

Objectives: To investigate the role of nurse-led, goal-directed lung physiotherapy on the prognosis of patients with sepsis caused by Acinetobacter baumannii pulmonary infection., Methods: Patients with sepsis caused by A. baumannii pulmonary infection were recruited and divided into a control group (phase 1) and a treatment group (phase 2). Both groups received standard therapy for sepsis, and patients in phase 2 also received nurse-led, goal-directed lung physiotherapy. The primary outcome measure was 28-day mortality., Results: Among 742 patients with sepsis, 201 were diagnosed with A. baumannii pulmonary infection. Compared with patients in phase 1, patients in phase 2 had a significantly shorter duration of mechanical ventilation {median 4 (interquartile range (IQR) 3-5] vs 5 (IQR 3-12) days; P = 0.004}, lower intensive care unit (ICU) mortality [13.6% (18/132) vs 27.5% (19/69); P = 0.016] and lower 28-day mortality [21.2% (28/132) vs 37.7% (26/69); P = 0.012]. As a protective factor, nurse-led, goal-directed lung physiotherapy (odds ratio 0.341, 95% confidence interval 0.155-0.751; P = 0.008) was an independent risk factor for 28-day mortality., Conclusions: Nurse-led, goal-directed lung physiotherapy shortened the duration of mechanical ventilation and ICU stay, and decreased ICU mortality and 28-day mortality in patients with sepsis caused by A. baumannii pulmonary infection., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The risk factors and outcomes of patients with bloodstream infections (BSIs) caused by Acinetobacter baumannii are major concerns in clinical therapy. Multicenter case-control studies were performed to compare the clinical characteristics of 47 A. baumannii BSI patients and 124 matched controls with nonbloodstream A. baumannii infections and the clinical and molecular characteristics of BSI survivors and nonsurvivors. Additionally, the mortality of BSIs was assessed. The clinical characteristics, including neutropenia, ICU admission prior to positive culture, primary infection in the central nervous system, and carbapenem use prior to positive culture, were independently associated with BSI caused by A. baumannii. The mortality of the BSI patients was significantly higher than that of the controls. A high Pitt bacteremia score was found to be an independent predictor of mortality in the BSI patients. The healthcare-associated factors, disease severity level, or antibiotic usage increased the risks of A. baumannii BSI and related mortality., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to understand the role of bactericidal permeability increasing protein (BPI) in the pathogenesis of experimental murine colitis., Methods: We used the Cre-LoxP system to generate BPI knockout (BPI KO) mice. Acute colitis was induced in BPI KO mice and wild-type (WT) mice by subjecting the mice to 5% dextran sulfate sodium (DSS). Mice were observed for symptoms of experimental colitis. The survival of BPI KO mice to infection with Acinetobacter baumannii , a gram-negative bacterium, was also assessed., Results: Southern blot, RT-PCR, and western blot results showed that the 2 nd and 3 rd exons of the murine Bpi gene were knocked out systemically, confirming successful construction of the BPI KO mouse. BPI KO mice subjected to DSS showed increased symptoms of experimental colitis, increased colonic mucosal damage, increased epithelial permeability, elevated levels of serum LPS, and a disrupted fecal microbiome as compared with WT mice. Furthermore, BPI KO mice challenged intraperitoneally with A. baumannii died sooner than WT mice, and the total number of bacteria in the abdominal cavity, spleen, and liver was increased in BPI KO mice as compared to WT mice., Conclusions: We successfully generated BPI KO mice. The BPI KO mice developed worse colitis than WT mice by increased colitis symptoms and colonic mucosal damage, elevated levels of serum LPS, and a disrupted microbiome. BPI could be a potential target for treatment of ulcerative colitis in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kong, Lv, Kang, An, Liu and Zhang.)

Patients with Acinetobacter baumannii bacteremia treated with antipseudomonal cephalosporins showed higher 14-day mortality than patients treated with antipseudomonal carbapenems. We hypothesized that the bacterial membrane vesicles (BMVs) induced by antipseudomonal cephalosporins are more virulent than BMVs induced by antipseudomonal carbapenems.To simulate the clinical condition with inadequate antimicrobial treatment, carbapenem-resistant A. baumannii was treated with ceftazidime (an antipseudomonal cephalosporin) or imipenem (an antipseudomonal carbapenem) at 1/2 the minimum inhibitory concentration. BMVs and BMV-carried lipopolysaccharide were measured by nanoparticle tracking analysis and western blotting, respectively. Cytokine expression in RAW264.7 macrophages or mice serum induced by the BMVs was determined by ELISA, fluorescent bead-based immunoassay or western blotting. The virulence of the BMVs was assessed in mice. Liquid chromatography tandem-mass spectrometry was used to determine the protein contents of the BMVs.We found that ceftazidime induced a higher number of BMVs (CAZ-BMV), which carried more LPS, and induced higher expression levels of iNOS, IL-1β, and IL-6 in macrophages, higher expression of many cytokines in mice, more neutrophil infiltration in lung interstitium, and higher mortality in mice than imipenem-induced BMVs (IMP-BMV). When adjusted to same amount of LPS, CAZ-BMV still led to higher mortality than IMP-BMV. Proteomic analysis revealed different protein contents in CAZ-BMV and IMP-BMV. In conclusion, A. baumannii BMVs induced by ceftazidime are more virulent than BMVs induced by imipenem.

Background: Pandrug-resistant Acinetobacter baumannii (PDRAB) is increasingly being reported as a nosocomial pathogen worldwide, but determining its clinical impact is challenging., Aim: To assess the spectrum of excess mortality attributable to PDRAB infection in acute care settings., Methods: This four-year cohort study was conducted in a tertiary-care referral hospital in Greece to estimate excess in-hospital mortality due to PDRAB infection by comparing patients infected to those colonized with PDRAB by means of competing risks survival analysis., Findings: The study cohort comprised 91 patients (median age: 67 years; 77% men). For most patients, PDRAB was first isolated in the intensive care unit (ICU) (N = 51; 57%) or following ICU discharge (N = 26; 29%). Overall in-hospital mortality was 68% (95% confidence interval (CI): 57.5-77.5%). PDRAB-infected patients (N = 62; 68%) and PDRAB-colonized patients (N = 29; 32%) had similar baseline characteristics, but the absolute excess risk of 30-day mortality in infected patients compared to colonized patients was 34% (95% CI: 14-54%). Multivariable competing risks regression showed that PDRAB infection significantly increased the daily hazard of 30-day in-hospital death (cause-specific hazard ratio (csHR): 3.10; 95% CI: 1.33-7.21) while simultaneously decreasing the daily rate of discharge (csHR: 0.24; 95% CI: 0.08-0.74), thereby leading to longer hospitalization. Stronger effects were observed for bloodstream infections., Conclusion: New effective antimicrobials would be expected to prevent mortality in one of every three patients treated for PDRAB infection and reduce their length of hospitalization. However, available therapeutic options remain extremely limited and emphasis on preventing healthcare-associated transmission of PDRAB is ever more important., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: The impact of appropriate antimicrobial therapy for A. baumannii bacteremic pneumonia has not been well established due to the inclusion of the three phenotypically indistinguishable Acinetobacter species and confounding factors including underlying diseases and severity of infection. This retrospective study aimed to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality in A. baumannii bacteremic pneumonia patients after adjusting for risk factors., Methods: This study was conducted at five medical centers in Taiwan between July 2012 and June 2016. A. baumannii species identification was performed using reference molecular methods. Risk factors for 14-day mortality were analyzed via logistic regression. The interaction between the Acute Physiology and Chronic Health Evaluation (APACHE) II score and appropriate antimicrobial therapy was assessed using the logistic model., Results: A total of 336 patients with monomicrobial A. baumannii bacteremic pneumonia were included in this study. The overall 14-day mortality rate was 47.3%. The crude mortality of appropriate antimicrobial therapy was 35.9% (57 of 151 patients). Appropriate antimicrobial therapy was associated with a lower mortality after multivariate adjustment (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.34-0.97; p = 0.04), and the effect was influenced by APACHE II score (OR for interaction term, 0.0098; 95% CI, 0.0005-0.1885; p = 0.002). Further analysis demonstrated that appropriate antimicrobial therapy significantly reduced 14-day mortality among the patients with an APACHE II score > 35 (OR 0.0098; 95% CI 0.0005-0.1885)., Conclusion: Appropriate antimicrobial therapy decreases 14-day mortality of the most severely ill patients with A. baumannii bacteremic pneumonia.

Background: Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors and overall mortality for MDR/XDR Acinetobacter baumannii infected pediatric patients., Methods: This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children's Hospital in China from December 2014 to May 2018. Acinetobacter baumannii clinical isolates were recovered from different specimens including blood, sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, ascites, hydrothorax, and urine. Antibiotic susceptibility test was determined according to the Clinical and Laboratory Standards Institute interpretive criteria. Clinical and biological data were obtained from the patients' medical records., Results: 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 male in the case group. The overall mortality rate was 29.4%, while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2% ± 3.61% vs. 9.15% ± 6.21%, P = 0.029), higher CD4+ T cell ratio (39.67% ± 12.18% vs. 32.66% ± 11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/mL vs. 0.1 (0.1, 22.99)pg/mL, P = 0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890-0.981; P = 0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425-870.574; p = 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients., Conclusion: MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality. Bloodstream and central nervous system infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality.

Objective: To describe the clinical features, outcomes, and molecular epidemiology of an outbreak of multidrug resistant (MDR) A. baumannii., Methods: We performed a retrospective analysis of all MDR A. baumannii isolates recovered during an outbreak from 2011 to 2015 in a tertiary care cancer hospital. Cases were classified as colonized or infected. We determined sequence types following the Bartual scheme and plasmid profiles., Results: There were 106 strains of A. baumannii isolated during the study period. Sixty-six (62.3%) were considered as infection and 40 (37.7%) as colonization. The index case, identified by molecular epidemiology, was a patient with a drain transferred from a hospital outside Mexico City. Ninety-eight additional cases had the same MultiLocus Sequence Typing (MLST) 758, of which 94 also had the same plasmid profile, two had an extra plasmid, and two had a different plasmid. The remaining seven isolates belonged to different MLSTs. Fifty-three patients (50%) died within 30 days of A. baumanniii isolation: 28 (20%) in colonized and 45 (68.2%) in those classified as infection (p<0.001). In multivariate regression analysis, clinical infection and patients with hematologic neoplasm, predicted 30-day mortality. The molecular epidemiology of this outbreak showed the threat posed by the introduction of MDR strains from other institutions in a hospital of immunosuppressed patients and highlights the importance of adhering to preventive measures, including contact isolation, when admitting patients with draining wounds who have been hospitalized in other institutions., Competing Interests: The authors have declared that no competing interests exist.

Acinetobacter baumannii has emerged as an important etiological agent of hospital-related infections, especially nosocomial pneumonia. The virulence factors of this bacterium and their interactions with the cells and molecules of the immune system just recently began to be extensively studied. Here, we investigated the impact of alveolar macrophages on A. baumannii pneumonia using a mouse model of infection and a flexible tissue culture system. We hypothesized that depletion of macrophages would enhance sepsis and severity of A. baumannii disease. We showed that macrophages are important for modulating the antibacterial function of neutrophils and play an important role in eradicating A. baumannii infection in vivo Our findings suggest that in the absence of macrophages in the lungs, A. baumannii replicates significantly, and host proinflammatory cytokines are considerably reduced. Neutrophils are abundantly recruited to pulmonary tissue, releasing high amounts of reactive oxygen species and causing extensive tissue damage. The ability of A. baumannii to form biofilms and resist oxidative stress in the respiratory tract facilitates systemic dissemination and ultimately death of infected C57BL/6 mice. These results provide novel information regarding A. baumannii pathogenesis and may be important for the development of therapies aimed at reducing morbidity and mortality associated with this emerging bacterial pathogen., (Copyright © 2020 American Society for Microbiology.)

Colistin remains a last-line antibiotic for the treatment of infections by multidrug-resistant Acinetobacter species. However, mortality rates are high in patients with Acinetobacter infection receiving colistin treatment. This multicentre study evaluated whether colistin susceptibility, additional antimicrobial agents or other prognostic factors influenced the clinical outcomes of patients receiving colistin treatment for Acinetobacter bacteraemia. This retrospective study enrolled 122 adults receiving colistin for monomicrobial Acinetobacter bacteraemia at six medical centres in the ACTION Study Group over an 8-year period. Clinical information, antimicrobial susceptibility and colistin resistance determinants were analysed. The primary outcome measure was 14-day mortality. Among 122 patients, 18 and 104 were infected with colistin-resistant (ColR) isolates [minimum inhibitory concentration (MIC) ≥4 mg/L] and colistin-susceptible (ColS) isolates (MIC ≤2 mg/L), respectively. Patients infected with ColR and ColS isolates did not differ significantly with regard to Charlson comorbidity index, invasive procedures, sources of bacteraemia, disease severity and 14-day mortality rate (44.4% vs. 34.6%; P = 0.592). No specific additional antimicrobial agent was independently associated with higher or lower mortality. Coronary artery disease, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and bacteraemia caused Acinetobacter baumannii were independent risk factors associated with 14-day mortality. Mechanisms of colistin resistance were associated with amino acid variants in the pmrCAB operon. Finally, previously unreported Acinetobacter nosocomialis amino acid variants related to colistin resistance were identified. In conclusion, colistin susceptibility and colistin combination antimicrobial treatment were not associated with decreased 14-day mortality in patients with Acinetobacter bacteraemia receiving colistin treatment., (Copyright © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

We examined microbiological and clinical characteristics of invasive Acinetobacter infection occurring in four hospitals located in the Minami-Ibaraki Area. Glucose-non-fermentative Gram-negative bacilli isolated from the blood and the cerebrospinal fluid in independent cases between 2001 and 2014 were consecutively collected and those possibly to be Acinetobacter species were re-identified using molecular methods. Of 158 strains identified as Acinetobacter species, 155 were classified into 16 officially designated species, including 42 Acinetobacter pittii and 40 Acinetobacter baumannii. Imipenem non-susceptibility was detected only in 4 strains, none of which demonstrated multidrug resistance. Retrospective analyses of 154 cases for which medical records were fully available showed that the most common cause of infection was primary bloodstream infection (134 cases), of which 128 were related to intravascular catheter use. The mortality on day 28 after the onset was independently associated with cerebrovascular disease, moderate to severe renal disease, the Pitt bacteremia score, and infection other than primary bloodstream infection but not with appropriate empiric antimicrobial therapy. Isolation of A. baumannii was significantly associated with septic shock but not with the 28-day mortality. These findings, obtained in a region where drug-resistant Acinetobacter strains were much less prevailing, indicated that non-baumannii Acinetobacter species were common pathogens, that the most predominant cause of invasive Acinetobacter infection was intravascular catheter-related infection, that virulence of A. baumannii might be higher than those of other species but its association with mortality was unclear, and that administration of broad-spectrum antibiotics targeting Acinetobacter species might be deferrable in a certain situation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Acinetobacter baumannii has become a common pathogen causing hospital-acquired infections (HAIs). Although acquiring any nosocomial infection is associated with increased mortality, we do not know if the acquisition of Acinetobacter infection confers a worse prognosis as compared to non-Acinetobacter-related HAI. The aim of the current study is to compare the clinical outcomes of ventilator-associated pneumonia (VAP) and central line associated blood stream infections (CLABSIs) caused by A. baumannii with those caused by other bacterial pathogens., Materials and Methods: This prospective cohort study was conducted among critically ill adults admitted to a tertiary care hospital in South India from January 2013 to June 2014. We enrolled patients who developed new-onset fever ≥48 h after admission and fulfilled pre-specified criteria for VAP or CLABSI. The patients were followed up until the primary outcomes of death or hospital discharge., Results: During the study period, 4047 patients were admitted in the intensive care units, among which 129 eligible HAI events were analysed. Of these, 95 (73.6%) were VAP, 34 (26.4%) were CLABSI, 78 (60.4%) were A. baumannii-related HAI (AR-HAI) and 51 (39.6%) were non-A. baumannii-related HAI (NAR-HAI). Mortality among AR-HAI was 57.6% compared to 39.2% in NAR-HAI (P = 0.04) which on multivariate analysis did not achieve statistical significance, although the trend persisted (odds ratio [OR] = 4.2, 95% confidence interval [CI]: 0.95-18.4, P = 0.06). The acquisition of VAP due to A. baumannii was associated with poor ventilator outcomes even after adjusting for confounders (adjusted OR = 3.5, 95% CI: 1.07-11.6, P = 0.04)., Conclusion: In our cohort of critically ill adults with VAP and CLABSI, AR-HAI was associated with poor ventilator outcomes and a trend towards higher mortality. These findings add to the evidence suggesting that A. baumannii is a dangerous pathogen, perhaps even more so than others., Competing Interests: None

Tigecycline (TGC) and cefoperazone/sulbactam (CPS) both have been shown good in vitro activity against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. We aim to compare the efficacy of TGC versus CPS for CRAB infections. We conducted a retrospective cohort study of patients with CRAB at a single center in China from 2013 to 2015. Outcomes comprised in-hospital mortality, clinical and microbiological response. The method of inverse probability of treatment weighting and multivariable logistic regression analysis incorporated with propensity score were employed to estimate the effect of treatment groups. There were 130 subjects included in our study. The patients in TGC, CPS and TGC plus CPS combination group were 42, 66, and 22, respectively. After adjustment, in-hospital mortality was lower in CPS group than TGC group (weighted OR 0.173; 95% CI 0.06-0.497; P=0.001) but without differences in clinical success and microbiological eradication (P>0.05). TGC monotherapy had a similar outcome with TGC plus CPS combination group. This is the first study comparing the efficacy of tigecycline and cefoperazone/sulbactam for CRAB infections. Cefoperazone/sulbactam appears to be more efficacious than tigecycline during treatment.

Background: Drug-resistant Acinetobacter species present serious therapeutic and infection control policy challenges globally. Although aminoglycosides have played a crucial role in the treatment of infections with multidrug-resistant (MDR) Acinetobacter spp., recent reports indicate that these bacteria are developing resistance to aminoglycosides around the globe., Objectives: To determine the association between amikacin resistance and clinical outcomes of patients. The minimum inhibitory concentrations (MICs) of amikacin against Acinetobacter spp. and genes associated with resistance were also investigated., Methods: Clinical information from 107 patients with Acinetobacter spp. cultured from clinical specimens was recorded during ward rounds at an academic complex hospital in KwaZulu-Natal Province, South Africa, including clinical outcomes, history of antibiotics prescribed and microbiological investigations. The 107 Acinetobacter isolates were investigated for susceptibility to antimicrobial agents in use at local hospitals. Genes related to amikacin resistance (aphA6 and aacA4) were investigated by polymerase chain reaction (PCR) and sequencing. Analysis was performed on the relationship between clinical outcomes and antimicrobial resistance patterns, as well as on the amikacin MICs in resistant isolates (n=6) v. their PCR results., Results: The majority (5/6, 83.3%) of patients with amikacin-resistant Acinetobacter infection were discharged, and 1/6 (16.7%) died. No underlying clinical factors were significantly associated with clinical outcome. Amikacin resistance was observed in 6/107 isolates (5.6%), with MICs of 32 µg/mL (n=3) and ≥64 µg/mL (n=3) for the amikacin-resistant isolates. All 6 of these isolates were also extensively drug-resistant (XDR). The aphA6 gene (797 base pair) was detected in all amikacin-resistant isolates., Conclusions: Most tested Acinetobacter isolates were susceptible to amikacin, underscoring the crucial role of this antibiotic in the treatment of MDR Acinetobacter spp. in our hospital. The emergence of XDR isolates is of serious concern and necessitates close monitoring and surveillance.

Objective: The objective of this works was to assess the global prevalence of multidrug-resistance among A. baumannii causing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), and describe its associated mortality., Methods: We performed a systematic search of four databases for relevant studies. Meta-analysis was done based on United Nations geoscheme regions, individual countries and study period. We used a random-effects model to calculate pooled prevalence and mortality estimates with 95% confidence intervals (CIs), weighted by study size., Results: Among 6445 reports screened, we identified 126 relevant studies, comprising data from 29 countries. The overall prevalence of multidrug-resistance among A. baumannii causing HAP and VAP pooled from 114 studies was 79.9% (95% CI 73.9-85.4%). Central America (100%) and Latin America and the Caribbean (100%) had the highest prevalence, whereas Eastern Asia had the lowest (64.6%; 95% CI, 50.2-77.6%). The overall mortality estimate pooled from 27 studies was 42.6% (95% CI, 37.2-48.1%)., Conclusions: We observed large amounts of variation in the prevalence of multidrug-resistance among A. baumannii causing HAP and VAP and its mortality rate among regions and lack of data from many countries. Data from this review can be used in the development of customized strategies for infection control and antimicrobial stewardship., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Carbapenem-resistant Acinetobacter baumannii (CR-Ab) has become a worrying health care problem, mainly in developing countries, such as Brazil. The objective was to investigate the prevalence and prognostic factors for CR-Ab infections at a Brazilian university hospital and examine the impact of inappropriate antimicrobial therapy on patient outcome., Methods: A retrospective study on hospitalized patients with CR-Ab infections was carried out from January 2013 to December 2017. An epidemiologic analysis was carried out to determine the frequency of infections, the epidemiologic indicators by year, the risk factors for 30-day mortality, and the impact of inappropriate therapy., Results: A total of 489 patients were included in the study. A rate of 0.7 per 1,000 patient-day CR-Ab infections was observed, mostly in the lungs (54.7%), and predominantly in the adult intensive care unit. The occurrence of infections by CR-Ab per 1,000 patient-days in November 2014 exceeded the established control limit, confirming an outbreak., Conclusions: The prevalence of CR-Ab increased in the investigated hospital, passing to an endemic pathogen with a direct impact on mortality and the control of these strains., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Clinical characteristics and risk factors for mortality of Acinetobacter bacteremia in cirrhotic patients have not been investigated., Methods: Acinetobacter bacteremia cases from four medical centers were collected from 2009 to 2014, to compare between patients with and without liver cirrhosis. Risk factors for mortality of Acinetobacter bacteremia among cirrhotic patients were identified using multivariate logistic regression., Results: Among the patients with Acinetobacter bacteremia, 72 had liver cirrhosis and 816 had not. Patients with cirrhosis were younger (57.5 [50-71] vs. 72 [50.25-71], p < 0.001), had more solid tumor (51.4% vs. 31.4%, p = 0.001), lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (17 [12-24] vs. 20 [13-28], p = 0.012), less sourced from pneumonia (19.4% vs. 35.8%, p = 0.008), and less caused by Acinetobacterbaumannii (33.3% vs. 50.6%, p = 0.007) than those without. After matching for age, sex, and causative pathogens, the 30-day mortality (34.7% vs. 29.2%, p = 0.592) and APACHE II scores (17 vs. 17, p = 0.769) were not significant. APACHE II score (odds ratio [OR], 1.146; 95% confidence interval [CI], 1.035-1.268; p = 0.009), bacteremia caused by A. baumannii (OR, 20.501; 95% CI, 2.301-182.649; p = 0.007), and solid tumor (OR, 18.073; 95% CI, 1.938-168.504; p = 0.011) were independent risk factors for 30-day mortality of cirrhotic patients with Acinetobacter bacteremia., Conclusion: Even though cirrhotic patients with Acinetobacter bacteremia were younger and had lower APACHE II scores than non-cirrhotic patients, the mortality rates were insignificantly different between the two groups., (Copyright © 2018. Published by Elsevier B.V.)

Carbapenem resistant Acinetobacter baumannii (CRAB) is a significant cause of hospital acquired bloodstream infections in patients with hematological malignancies. Data regarding outcomes in this group of patients are limited. We retrospectively analyzed mortality risk factors of hospitalized hematological patients with CRAB bacteremia in our center. Among 46 included patients, overall 7-day mortality was 72% (33/46). Risk factors for 7-day mortality in multivariate analysis were higher infection severity score (SOFA score) at presentation (OR 1.481, 95% CI 1.091-2.012, p  = .012) while appropriate antibiotic therapy within 48 h was protective (OR 0.052, 95% CI 0.005-0.590, p  = .017). Inappropriate antibiotic therapy within 24 h was not significantly associated with 7-day mortality nor was absolute neutrophil count. Thirty-day mortality was 96% (44/46). CRAB bacteremia in hematological patients is associated with extremely high mortality, regardless of therapy. Infection control measures and antimicrobial stewardship aiming to prevent this infection of dismal prognosis are of major importance.

Aims: Acinetobacter baumannii has become an important nosocomial pathogen that causes invasive infections. We conducted a retrospective study to evaluate the risk factors for mortality due to A. baumannii bacteremia in children. Materials and Methods: We reviewed data from Seoul National University Children's Hospital from 2002 to 2013 for children with A. baumannii bacteremia, including age, gender, underlying disease, associated site of infection, duration of hospitalization, presence of neutropenia, and antibiotic susceptibility data. The outcome measures were the 7- and 30-day mortality rates. Results: Among 74 A. baumannii bacteremia cases, 35.1% were carbapenem nonsusceptible. Common comorbidities were malignancy or hematologic diseases (28.4%), followed by gastrointestinal/hepatobiliary diseases (21.6%). A total of 47.3% of patients had isolated bacteremia, and in 33.8% of patients, pneumonia accompanied bacteremia. The mortality rates were 18.9% at 7 days and 35.1% at 30 days. The significant associated factors for 30-day mortality were carbapenem nonsusceptibility (adjusted hazard ratio [ a HR]: 1.28, 95% confidence interval [CI]: 1.10-11.82, p  = 0.034), neutropenia ( a HR: 1.68, 95% CI: 1.60-18.03, p  = 0.007), and prior intensive care unit (ICU) admission ( a HR: 1.15, 95% CI: 1.03-9.73, p  = 0.045). The mortality rate among neutropenic patients with inappropriate empirical antibiotics was higher than that among patients with appropriate empirical antibiotics (90.1% vs. 33.3%, p  = 0.031). Conclusions: We identified carbapenem nonsusceptibility, neutropenia, and prolonged ICU stay as independent risk factors for mortality due to A. baumannii bacteremia in children. An early administration of appropriate antibiotics should be enacted, especially in patients with neutropenia.

Background: Post-operative central nervous system infection (PCNSI) caused by multi-drug-resistant/extensively drug-resistant (MDR/XDR) Acinetobacter baumannii is a severe complication. This study aimed to analyze the clinical presentation and treatment of this disorder. Patients and Methods: A retrospective study that recruited patients having PCNSI caused by MDR/XDR Acinetobacter baumannii was performed at our institute. The patients' demographic information and clinical data were recorded and analyzed. To analyze treatment, we assigned patients to different groups according to whether they had intraventricular/intrathecal injection of antibiotic agents or cerebrospinal fluid (CSF) drainage therapy. Results: Twenty-four patients were included. The risk factors were classified into two categories: environmental factors (intensive care unit stay, tracheal intubation or tracheotomy, positive culture of MDR/XDR Acinetobacter baumannii from other samples) or infectious approaches (CSF drainage, incision CSF leakage). Cerebrospinal fluid sterilization was achieved in 13 patients (54.2%) and the 30-day mortality was 50%. In the seven patients having intraventricular/intrathecal injection of antibiotic agents, the CSF sterilization rate was 71.4% (5/7) and 30-day mortality was 28.6% (2/7), compared with 47.1% (8/17; p  = 0.27) and 58.8% (10/17; p  = 0.18) in patients having only intravenous antibiotic agents. In 19 patients having CSF drainage therapy for PCNSI, the CSF sterilization rate was 63.2% (12/19) and 30-day mortality was 42.1% (8/19) compared with 20% (1/5; p  = 0.08) and 80% (4/5; p  = 0.13) in the remaining patients. Conclusions: The risk factors for PCNSI caused by Acinetobacter baumannii can be classified in two categories: environmental factors or infectious approaches. Both intraventricular/intrathecal injection of antibiotic agents and CSF drainage are helpful for CSF sterilization.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) tops the list of threats to human health. Studies exploring predictors of mortality in patients with CRAB infection produced conflicting results., Methods: A systematic search of the PubMed, Embase, and the Cochrane Library databases was performed from inception to June 2018 to identify studies reporting mortality predictors in patients infected with CRAB. Two authors independently assessed trials for inclusion and data extraction., Results: A total of 19 observational studies were enrolled in this study. Factors associated with mortality of patients infected with CRAB were inappropriate empirical antimicrobial treatment (odds ratio [OR], 5.04; 95% confidence interval [CI], 2.56-9.94), septic shock (OR, 5.65; 95% CI, 2.35-13.57), chronic liver disease (OR, 2.36; 95% CI, 1.33-4.16), chronic renal disease (OR, 2.02; 95% CI, 1.37-2.99), hypertension (OR, 1.74; 95% CI, 1.08-2.80), neutropenia (OR, 3.31; 95% CI, 1.25-8.77), immunosuppressant use (OR, 3.15; 95% CI, 1.94-5.11), total parenteral nutrition (OR, 1.66; 95% CI, 1.08-2.56), and intubation (OR, 5.03; 95% CI, 2.33-10.87). Acute Physiology and Chronic Health Evaluation II score at admission and Pitt bacteremia score at the onset of CRAB bacteremia were higher in nonsurvivors., Conclusions: Our study suggests that severity of baseline condition and receiving inappropriate experience antibiotic therapy are major risk factors for higher mortality in patients with CRAB infections. These findings may help clinicians to take appropriate preventive measures and decrease mortality in such patients., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy., Methods: This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality., Results: Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118-.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021-9.202])., Conclusions: Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy., Clinical Trials Registration: NCT01732250., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Multidrug-resistant (MDR) Acinetobacter baumannii infections have high mortality rates and few treatment options. Synergistic drug combinations may improve clinical outcome and reduce further emergence of resistance in MDR pathogens. Here we show an unexpected potent synergy of two translation inhibitors against the pathogen: commonly prescribed macrolide antibiotic azithromycin (AZM), widely ignored as a treatment alternative for invasive Gram-negative pathogens, and minocycline, among the current standard-of-care agents used for A. baumannii., Methods: Media-dependent activities of AZM and MIN were evaluated in minimum inhibitory concentration assays and kinetic killing curves, alone or in combination, both in standard bacteriologic media (cation-adjusted Mueller-Hinton Broth) and more physiologic tissue culture media (RPMI), with variations of bicarbonate as a physiologic buffer. Synergy was calculated by fractional inhibitory concentration index (FICI). Therapeutic benefit of combining AZM and MIN was tested in a murine model of A. baumannii pneumonia. AZM + MIN synergism was probed mechanistically by bacterial cytological profiling (BCP), a quantitative fluorescence microscopy technique that identifies disrupted bacterial cellular pathways on a single cell level, and real-time kinetic measurement of translation inhibition via quantitative luminescence. AZM + MIN synergism was further evaluated vs. other contemporary high priority MDR bacterial pathogens., Findings: Although two translation inhibitors are not expected to synergize, each drug complemented kinetic deficiencies of the other, speeding the initiation and extending the duration of translation inhibition as verified by FICI, BCP and kinetic luminescence markers. In an MDR A. baumannii pneumonia model, AZM + MIN combination therapy decreased lung bacterial burden and enhanced survival rates. Synergy between AZM and MIN was also detected vs. MDR strains of Gram-negative Klebsiella pneumoniae and Pseudomonas aeruginosa, and the leading Gram-positive pathogen methicillin-resistant Staphylococcus aureus., Interpretation: As both agents are FDA approved with excellent safety profiles, clinical investigation of AZM and MIN combination regimens may immediately be contemplated for optimal treatment of A. baumannii and other MDR bacterial infections in humans. FUND: National Institutes of Health U01 AI124326 (JP, GS, VN) and U54 HD090259 (GS, VN). IC was supported by the UCSD Research Training Program for Veterinarians T32 OD017863., (Copyright © 2019. Published by Elsevier B.V.)

Background/purpose: Diabetes is associated with increased mortality in Acinetobacter baumannii (AB) complex infection. This study investigated the risk factors and relationship of diabetic status and glycemic indices to mortality in patients with carbapenem-resistant (CR) AB complex bacteremia., Methods: Relationship of glycemic indices to mortality were compared in adult diabetes (DM) and nondiabetes (non-DM) patients with CRAB complex bacteremia hospitalized from January 2010 to December 2015 in MacKay Memorial Hospital, Taiwan., Results: Of 317 patients with CRAB complex bacteremia, 146 (46.06%) had diabetes. DM patients were elderly (mean age of 69.23 years) and the mortality rate was higher (64.38% vs. 52.05%, p = 0.036) than in non-DM patients. By multivariate analysis, septic shock was associated with increased mortality in DM patients. Hypoglycemia was associated with increased mortality in non-DM patients only (100% vs. 50.33%, p = 0.006). The lowest mortality was for the blood glucose range 70-100 mg/dL in non-DM patients (43.24%) and 100-140 mg/dL for DM patients (56.52%). Increased glycemic variability (coefficient of variation (CV) > 40% compared to < 20%) was associated with increased mortality in non-DM patients (86.36% vs. 47.12%, p = 0.003)., Conclusion: Effects of dysglycemia on mortality due to CRAB complex bacteremia differ according to diabetic status. Mortality was higher in DM patients. In non-DM patients, hypoglycemia and increased CV were associated with increased mortality. The lowest mortality was for the blood glucose range 70-100 mg/dL in non-DM patients and 100-140 mg/dL for DM patients., (Copyright © 2018. Published by Elsevier B.V.)

Backgrounds: Infectious complication is an important cause of poor outcome of lung transplantation (LT). Infections with Acinetobacter baumannii ( A. baumannii ) are problematic, because of limited therapeutic option due to increasing resistance to antibiotics. However, there are few studies on A. baumannii infection in lung transplant recipients. Thus, we aimed to investigate epidemiology and risk factors for infection with A. baumannii in lung transplant recipients. Methods: Lung transplant recipients ≥18 years of age in a university hospital were enrolled in this retrospective cohort study. Risk factors for infection with multidrug resistant A. baumannii and 90-day mortality were analysed. Results: Fifty-one of 96 lung transplant recipients experienced A. baumannii infection. Infected patients had a significantly higher 90-day mortality rate than uninfected (19.6% vs. 2.2%, p  = .009). High blood urea nitrogen (BUN) before transplantation (odds ratio [OR] 1.16; p  = .008), long duration of surgery (OR 1.16; p  = .029) and hypoalbuminemia before transplantation (OR 4.01; p  = .037) were independent risk factors for infection with multidrug resistant A. baumannii . On multivariate analysis, severe thrombocytopenia (OR 28.69; p  = .005), high serum creatinine (OR 1.48; p  = .042) and infection with multidrug resistant A. baumannii (OR 22.58; p  = .031) were independent risk factors for 90-day mortality. Conclusions: Prolonged surgery, high BUN and hypoalbuminemia before LT were significant risk factors for infection with multidrug resistant A. baumannii . Severe thrombocytopenia, high serum creatinine and infection with multidrug resistant A. baumannii infection were independent risk factors for 90-day mortality.

Objectives: This study aimed to assess the effectiveness of trimethoprim-sulfamethoxazole (TMP/SMX) as monotherapy for the treatment of carbapenem-resistant Acinobacter baumannii (A. baumannii) (CRAB) infections., Methods: This retrospective cohort study included patients receiving TMP/SMX as the main treatment for severe infections caused by CRAB, who were matched with patients treated with colistin or ampicillin-sulbactam (AMP/SUL) by age, Charlson score, department, and source of infection. Outcomes were compared among all patients and in a subgroup of propensity-score (PS) matched patients. The PS matching was performed using a match tolerance of 0.15 with replacement., Results: Fifty-three patients treated with TMP/SMX and 83 matched patients treated with colistin or AMP/SUL were included. Variables that were independently significantly associated with TMP/SMX treatment included admission for infection and septic shock, while abnormal cognition on admission and intensive care unit admission were associated with colistin or AMP/SUL treatment. All-cause 30-day mortality was lower with TMP/SMX compared with the comparator antibiotics among all patients (24.5%, 13 of 53 vs. 38.6%, 32 of 83, P=0.09) and in the PS-matched subgroup (29%, 9 of 31 vs. 55.2% 16 of 29, P=0.04). Treatment failure rates were not significantly different overall (34%, 18 of 53 vs. 42.4%, 35 of 83, P=0.339) and in the PS-matched subgroup (35.5%, 11 of 31 vs. 44.8%, 13 of 29, P=0.46). Time to clinical stability and hospitalization duration were significantly shorter with TMP/SMX. Patients treated with TMP/SMX probably had less severe infections than those treated with other antibiotics, even after matching., Conclusions: TMP/SMX might be a valuable treatment option for TMP/SMX-susceptible CRAB infections. Given the very limited available treatment options, further studies assessing its effectiveness and safety are necessary., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: Surgical site infection is an important complication in the postoperative period among liver transplant recipients. However, little is known about the risk factors in this patient group. Therefore, the objective of this study was to analyze the incidence and risk factors for surgical site infections among adult liver transplant recipients., Methods: Medical records of adult liver transplant recipients from January 1, 2009, to December 31, 2015, were analyzed in this retrospective cohort study., Results: We enrolled 156 recipients' medical records. Forty-two (26.9%) cases of surgical site infections were identified. The main isolated microorganisms were methicillin-resistant Staphylococcus species, extended spectrum β-lactamase-producing Klebsiella species, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Acinetobacter baumannii, and vancomycin-susceptible Enterococcus faecalis. We found that long operative times (≥487 minutes) and differences in body mass index between donor and recipient (≥1.3 kg/m 2 ) increased the risk for surgical site infections by approximately 5 times (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.5-11.8), and capillary glycemia ≥175 mg/dL in the first 96 postoperative hours increased the risk by approximately 3 times (OR, 2.97; 95% CI, 1.43-6.17)., Conclusions: There was a high incidence of surgical site infections among the studied population and that some risk factors identified differ from those reported in the scientific literature.

Background: Acinetobacter baumannii (Ab) is an important opportunistic pathogen in a hospital setting. The virulence varies among different clinical isolates, which can be measured by cytotoxicity assay or Galleria mellonella killing assay. However, these measurements are not suitable for routine clinical laboratory application. Thus, a putative marker for early prediction and intervention of these virulent isolates is desirable., Methods: PgaB is part of the pgaABCD cluster, which is considered to be essential for the biofilm formation and pathogenesis of Ab. Sixty-five non-repetitive Ab clinical isolates were randomly collected from respiratory tract specimens in our hospital, which were pgaB positive as determined by PCR. The mRNA expression level of pgaB was measured by quantitative real-time PCR, with Taqman probe targeting the conserved region of pgaB. 16S rRNA was used as an internal control. The virulence was determined by the ability to kill A549 human lung epithelial cells with different MOIs and different time points. The virulence was also determined by Galleria mellonella killing assay and analyzed by Kaplan-Meier survival analysis. The statistical analysis was performed with SPSS 13.0 and Graphpad Prism 5.0., Results: Sixty-five isolates were divided into pgaB high and low expression groups by the values of adjusted pgaB expression, the median values of which were 25.81 ± 6.34 (n = 41) and 4.16 ± 2.82 (n = 24), respectively (p < 0.05). The Ab virulence determined by cytotoxicity assay was significantly higher in the pgaB high expression group than in the low expression group (MOI = 100, incubated for 18 hours, p < 0.05). The killing rate of Galleria mellonella was significantly higher in the pgaB high expression group than in the low expression group (inoculum of 106 CFU/larva at 37°C, p < 0.05), with the median survival time of 40 hours and 75 hours, respectively., Conclusions: The adjusted expression level of pgaB was in agreement with the virulence of Ab in cytotoxicity assays and Galleria mellonella killing assay, thus it may be used potentially as a putative marker for early prediction of the virulence of Ab clinical isolates.

Objectives: Acinetobacter baumannii can cause severe nosocomial and community-acquired pneumonia. To study the pathogenesis of A. baumannii and to develop new treatments, appropriate mouse models are needed. Most reported mouse models of pulmonary A. baumannii infection are non-lethal or require mouse immunosuppression to enhance infection. These models are not suitable for studying host immune responses or evaluating immunotherapies., Methods: The virulence of 30 clinical isolates was assessed in mice. The most virulent isolate, SJZ24, was selected to develop a pneumonia model in immunocompetent mice. The cytokine mRNA expression in the lung was assessed with real-time PCR. The cell infiltration in bronchoalveolar lavage fluid (BALF) after SJZ24 infection was determined by flow cytometry. Vaccine efficacy was assessed using this model., Results: Intratracheal inoculation of SJZ24 (5 × 10 7  CFU) resulted in death in 100% of the mice (5/5). SJZ24-infected mice showed high bacterial burdens in blood and organs as well as severe lung-tissue damage. Infection with SJZ24 induced increased inflammatory cytokine expression in the lung and increased neutrophil infiltration in BALF. Immunization with inactivated whole cells of SJZ24 showed 100% protection (5/5) against A. baumanni infection in this model., Conclusions: We established a lethal pneumonia model in immunocompetent mice with hypervirulent A. baumannii isolate SJZ24. This model can be used to study the immune response to A. baumannii infection and to evaluate vaccine efficacy., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background/purpose: In 2017, the World Health Organization categorized carbapenem-resistant Acinetobacter baumannii (CRAB) as a priority 1, critical antibiotic-resistant bacteria. This study analyzed the clinical outcomes and investigated the molecular epidemiology of CRAB bacteremia in a medical center in Northern Taiwan., Methods: We collected 62 blood isolates from patients with CRAB bacteremia from January 2014 to December 2015 at MacKay Memorial Hospital and determined the clonal relationship using the PCR-based technique for molecular epidemiology. Medical charts were reviewed for clinical outcomes., Results: Fifty-six isolates harbored the bla OXA-51-like and bla OXA-23-like carbapenemase genes, 4 isolates harbor the bla OXA-51-like and bla OXA-24-like carbapenemase genes and 2 isolates harbored only the bla OXA-51-like gene. After sequencing, all four isolates of bla OXA-24-like carbapenemase gene were confirmed to be isolates of bla OXA-72 carbapenemase genes. In multivariate analysis in the 60 patients, the independent mortality risk factors of CRAB bacteremia included ≥65 years (elderly) (Odds ratio, 4.04, 95% CI, 1.10-14.83, p = 0.035), chronic kidney disease (4.36, 1.14-16.72, p = 0.032). Isolates harboring the bla OXA-72 gene had the same sequence type (ST218) and PFGE pulsotype raising the possibility of intra-hospital transmission, and all infected patients died., Conclusion: This study showed the clonal relationship of isolates harboring the carbapenemase gene in CRAB bacteremia. Patients with the ST218 strain harboring bla OXA-72 gene had high mortality. This warrants further research to determine the mechanism of virulence and risk factors in order to reduce mortality., (Copyright © 2018. Published by Elsevier B.V.)

Bloodstream infection caused by Acinetobacter baumannii has become a major clinical concern, especially multidrug-resistant A baumannii (MDRAB). The aim of this study was to identify the risk factors of nosocomial acquired MDRAB bacteremia and to determine the risk factors related to the mortality of patients with MDRAB bacteremia. Patients with nosocomial acquired A baumannii bacteremia were enrolled between January, 2013 and December, 2017 at the First Affiliated Hospital, School of Medicine, Zhejiang University. Medical records were reviewed, and the clinical and microbial characteristics were collected. Among the 338 patients suffering from A baumannii bacteremia, 274 patients were infected with MDRAB bacteremia. Bacteremia-related mortality was 46.4% for the overall sample; 56.2% for MDRAB bacteremia patients, 4.7% for non-MDRAB bacteremia patients. The identified risk factors for developing MDRAB bacteremia were previous exposure to carbapenems [odds ratio (OR) 5.78, P = .005] and penicillins+β-lactamase inhibitors (OR 4.29, P = .009). Primary bacteremia tended to develop non-MDR bacteremia (OR 0.10, P = .002). The risk factors for MDRAB bacteremia-related mortality were old age (OR 1.02, P = .036), a high Pitt bacteremia score (OR 1.32, P < .001), bacteremia occurring after severe pneumonia (OR 8.66, P < .001), while catheter-related infection (OR 0.47, P = .049) and operations for treating infection (OR 0.51, P = .043) may have a better outcome. Patients with MDRAB had a higher mortality rate. Patients with previous carbapenems and penicillins+β-lactamase inhibitor exposure are at an increased risk of MDRAB bacteremia, whereas patients with primary bacteremia tended to develop non-MDR bacteremia. The risk factors for MDRAB bacteremia-related mortality were old age, a high Pitt bacteremia score, and bacteremia occurring after severe pneumonia, whereas catheter-related infection and operations for the treatment of infection may have a better outcome.

Introduction: Acinetobacter species treatment often represents a challenge. The main objective of this study is identify predictors of ICU mortality in patients submitted to mechanical ventilation (MV)., Materials and Methods: Retrospective cohort study. Patients with MV > 48 h who developed a respiratory tract positive culture for Acinetobacter were included, and distinguished among colonized, ventilator-associated pneumonia (VAP) or ventilator-associated tracheobronchitis (VAT) patients. Primary outcome was ICU mortality., Results: 153 patients were in MV and presented positive culture for Acinetobacter calcoaceticus-baumanii complex, 70 of them with VAP, 59 with VAT and 24 patients were colonized. The factors related to ICU mortality were VAP (OR 2.2, 95% CI 1.1-4.5) and shock at the time of diagnosis (OR 4.8, 95% CI 1.8-2.3). In multivariate analysis, only SOFA score at the time of diagnosis (OR 1.06, 95% CI 1.03-1.09) was related with ICU mortality. A paired-matched analysis was performed to assess effect of dual therapy on outcomes, and no effect was found in terms of clinical cure, ICU or hospital mortality or duration of antimicrobial therapy., Conclusions: Previous comorbidities and degree of associated organic injury seem to be more important factors in the prognosis than double antibiotic therapy in patients with Acinetobacter-related respiratory infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Acinetobacter baumannii (Ab) is an important cause of healthcare-associated infections. Multilocus sequence typing (MLST) provides a highly discriminative typing method. We aimed to determine the clinical impact of Ab sequence types (ST) in patients with bloodstream infection (BSI)., Methods: Patients with Ab-BSI were followed prospectively from 2009 to 2014. We randomly selected one-third of non-duplicate bacteremic isolates for MLST and correlated the Ab ST with the clinical course. The primary outcome was all-cause in-hospital mortality., Results: We enrolled 148 patients. Seventy-seven (52.0%) of the isolates were ST2. Patients with ST2-BSI were less likely to be treated with appropriate empirical antimicrobial agents (31.1% vs. 60.6%; P < 0.001). They had greater mortality (66.2% vs. 40.8%; P = 0.003) than patients with non-ST2-BSI. In the multivariable analysis, ST2 independently predicted greater severity of infection (Pitt bacteremia score) (adjusted odds ratio (aOR), 3.38; 95% confidence interval (CI), 1.75-6.54; P < 0.001). Mediated by a higher Pitt bacteremia score (Sobel test P < 0.001), ST2 is an independent prognostic factor that predict mortality (aOR, 2.34; 95% CI, 1.07-5.11; P = 0.03)., Conclusions: ST2 was associated with high rates of inappropriate antimicrobial therapy, severe infection and mortality. Further studies are needed to confirm our findings and explore the potential of role of the virulence., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)