Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

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.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: A multi-centre clinical experience.

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.

Derivation and validation of a predictive mortality model of in-hospital patients with Acinetobacter baumannii nosocomial infection or colonization.

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.

Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study.

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.

Risk factors for bacteremic pneumonia and mortality (28-day mortality) in patients with Acinetobacter baumannii bacteremia.

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.

Association of capsular polysaccharide locus 2 with prognosis of Acinetobacter baumannii bacteraemia.

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.

Evaluationof the New Outer Membrane Protein A Epitope-based Vaccines for Mice Model of Acinetobacter baumannii Associated Pneumonia and Sepsis Infection.

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.

Association between mortality and highly antimicrobial-resistant bacteria in intensive care unit-acquired pneumonia.

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.

Effect of Delays in Concordant Antibiotic Treatment on Mortality in Patients With Hospital-Acquired Acinetobacter Species Bacteremia: Emulating a Target Randomized Trial With a 13-Year Retrospective Cohort.

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%.

Predictors of Acute Kidney Injury and 28-Day Mortality in Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia.

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.

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

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.

Effect of nurse-led, goal-directed lung physiotherapy on prognosis of patients with sepsis caused by Acinetobacter baumannii pulmonary infection.

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.

Risk factors and outcomes of bloodstream infections caused by Acinetobacter baumannii: a case-control study.

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.

Excess mortality due to pandrug-resistant Acinetobacter baumannii infections in hospitalized patients.

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.

Influence of severity of infection on the effect of appropriate antimicrobial therapy for Acinetobacter baumannii bacteremic pneumonia.

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.

Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: a retrospective study in the pediatric intensive care unit.

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.

High mortality in an outbreak of multidrug resistant Acinetobacter baumannii infection introduced to an oncological hospital by a patient transferred from a general hospital.

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.

Mortality from acinetobacter infections as compared to other infections among critically ill patients in South India: A prospective cohort study.

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.

Depletion of Alveolar Macrophages Increases Pulmonary Neutrophil Infiltration, Tissue Damage, and Sepsis in a Murine Model of Acinetobacter baumannii Pneumonia.

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.

Multicentre study of risk factors for mortality in patients with Acinetobacter bacteraemia receiving colistin treatment.

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.