Baumannii Ventilator-associated Pneumonia Research Articles

Co-Administration of High-Dose Nebulized Colistin for Acinetobacter baumannii Bacteremic Ventilator-Associated Pneumonia: Impact on Outcomes.

Acinetobacter baumannii (A. baumannii) is a difficult-to-treat (DTR) pathogen that causes ventilator-associated pneumonia (VAP) associated with high mortality. To improve the outcome of DTR A. Baumannii VAP, nebulized colistin (NC) was introduced with promising but conflicting results on mortality in earlier studies. Currently, NC is used at a much higher daily dose compared to the past. Nevertheless, there is little evidence on the effect of high-dose NC on the outcomes of A. baumannii VAPs, especially in the current era where the percentage of colistin-resistant A. baumannii strains is rising. We conducted a retrospective study comparing bacteremic A. baumannii VAP patients who were treated with and without NC co-administration and were admitted in the Intensive Care Unit of University Hospital of Ioannina from March 2020 to August 2023. Overall, 59 patients (21 and 38 with and without NC coadministration, respectively) were included. Both 28-day and 7-day mortalities were significantly lower in the patient group treated with NC (52.4% vs. 78.9%, p 0.034 and 9.5% vs. 47.4%, p 0.003, respectively). Patients treated with NC had a higher percentage of sepsis resolution by day 7 (38.1% vs. 13.5%, p 0.023) and were more likely to be off vasopressors by day 7 (28.6% vs. 8.1%, p 0.039). The addition of NC in the treatment regime of A. baumannii VAP decreased mortality.

Cefiderocol-containing regimens for the treatment of carbapenem-resistant A. baumannii ventilator-associated pneumonia: a propensity-weighted cohort study.

Cefiderocol is a novel β-lactam with activity against carbapenem-resistant Acinetobacter baumannii (CRAB), but its role in CRAB pulmonary infections is controversial due to limited evidence. To assess the association between cefiderocol-containing regimens treatment and 28-day mortality in carbapenem-resistant A. baumannii ventilator-associated pneumonia (VAP). An observational cohort study including critically ill COVID-19 patients with CRAB-VAP admitted to two ICUs of a large academic hospital in Rome between September 2020 and December 2022. The primary outcome was 28-day all-cause mortality. A propensity score was created to balance the cefiderocol- and non-cefiderocol-containing groups. A propensity-weighted multiple logistic regression model was calculated to evaluate risk factors for 28-day mortality. Survival curves were calculated using the Kaplan-Meier method. 121 patients were enrolled, 55 were treated with cefiderocol- and 66 with non-cefiderocol-containing regimens. The 28-day all-cause mortality was 56% (68/121). A statistically significant difference in 28-day mortality was found between cefiderocol- and non-cefiderocol- containing regimens groups (44% versus 67%, P = 0.011). In the propensity-adjusted multiple logistic regression, cefiderocol (OR 0.35 95% CI 0.14, 0.83) was a predictor of 28-day survival, Charlson comorbidity index (OR 1.36 95% CI 1.16, 1.78), SOFA score (OR 1.24 95% CI 1.09, 1.57) and septic shock (OR 3.71 95% CI 1.44, 12.73) were all associated with increased 28-day mortality. Cefiderocol-containing regimens were associated with reduced 28-day mortality in CRAB-VAP. The sample size and the observational design limit the study's conclusions. Future RCTs are needed to establish cefiderocol's definite role in these infections.

Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

Ventilator-Associated Pneumonia due to Drug-Resistant Acinetobacter baumannii: Risk Factors and Mortality Relation with Resistance Profiles, and Independent Predictors of In-Hospital Mortality.

Background and objectives: High mortality and healthcare costs area associated with ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii (A. baumannii). The data concerning the link between multidrug-resistance of A. baumannii strains and outcomes remains controversial. Therefore, we aimed to identify the relation of risk factors for ventilator-associated pneumonia (VAP) and mortality with the drug resistance profiles of Acinetobacter baumannii (A. baumannii) and independent predictors of in-hospital mortality. Methods: A retrospective ongoing cohort study of 60 patients that were treated for VAP due to drug-resistant A. baumannii in medical-surgical intensive care units (ICU) over a two-year period was conducted. Results: The proportions of multidrug-resistant (MDR), extensively drug-resistant (XDR), and potentially pandrug-resistant (pPDR) A. baumannii were 13.3%, 68.3%, and 18.3%, respectively. The SAPS II scores on ICU admission were 42.6, 48.7, and 49 (p = 0.048); hospital length of stay (LOS) prior to ICU was 0, one, and two days (p = 0.036), prior to mechanical ventilation (MV)—0, 0, and three days (p = 0.013), and carbapenem use prior to VAP—50%, 29.3%, and 18.2% (p = 0.036), respectively. The overall in-hospital mortality rate was 63.3%. In MDR, XDR, and pPDR A. baumannii VAP groups, it was 62.5%, 61.3%, and 72.7% (p = 0.772), respectively. Binary logistic regression analysis showed that female gender (95% OR 5.26; CI: 1.21–22.83), SOFA score on ICU admission (95% OR 1.28; CI: 1.06–1.53), and RBC transfusion (95% OR 5.98; CI: 1.41–25.27) were all independent predictors of in-hospital mortality. Conclusions: The VAP risk factors: higher SAPS II score, increased hospital LOS prior to ICU, and MV were related to the higher resistance profile of A. baumannii. Carbapenem use was found to be associated with the risk of MDR A. baumannii VAP. Mortality due to drug-resistant A. baumannii VAP was high, but it was not associated with the A. baumannii resistance profile. Female gender, SOFA score, and RBC transfusion were found to be independent predictors of in-hospital mortality.

Risk factors for mortality in ICU patients with Acinetobacter baumannii ventilator-associated pneumonia: impact of bacterial cytotoxicity.

Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) in intensive care unit (ICU) is associated with high morbidity and mortality in patients with critical illness. However, the literatures that focused on the short-term prognosis and the risk factors for mortality are limited. The aim of this study was to evaluate the risk factors for mortality in ICU patients with A. baumannii VAP. A retrospective cohort study was conducted in the medical/surgical ICU at Zhongshan Hospital in Shanghai, China. Adult patients meeting the criteria of A. baumannii VAP from January 2012 to October 2015 were enrolled. Apart from collecting clinical and microbiologic data, we performed biofilm-formation and cytotoxicity testing using A. baumannii strains which are isolated from patients. Multivariate logistic regression analysis was used to determine the independent risk factors for 30-day mortality in ICU. Seventy-eight patients were included in this study. The 30-day mortality rate in ICU for the patients was 37.2%. Multivariate analysis revealed that short-term mortality was significantly associated with prior surgery [OR, 0.277; 95% confidence interval (CI), 0.089-0.866; P=0.027], higher APACHEII score (OR, 1.140; 95% CI, 1.007-1.291; P=0.038) and an increased bacterial cytotoxicity (OR, 1.029 ; 95% CI, 1.001-1.058; P=0.047). The main finding of our study was that increased bacterial cytotoxicity might be a risk factor for short-term mortality in ICU patients with A. baumannii VAP.

High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial.

ObjectivesTo investigate the molecular epidemiology, antimicrobial susceptibility and carbapenem resistance determinants of Acinetobacter baumannii isolates from respiratory tract samples of patients diagnosed with ventilator-associated pneumonia (VAP) who were enrolled in the MagicBullet clinical trial.Methods A. baumannii isolates were prospectively cultured from respiratory tract samples from 65 patients from 15 hospitals in Greece, Italy and Spain. Susceptibility testing was performed by broth microdilution. Carbapenem resistance determinants were identified by PCR and sequencing. Molecular epidemiology was investigated using rep-PCR (DiversiLab) and international clones (IC) were identified using our in-house database.ResultsOf 65 isolates, all but two isolates (97%) were resistant to imipenem and these were always associated with an acquired carbapenemase, OXA-23 (80%), OXA-40 (4.6%), OXA-58 (1.5%) or OXA-23/58 (1.5%). Resistance to colistin was 47.7%. Twenty-two isolates were XDR, and 20 isolates were pandrug-resistant (PDR). The majority of isolates clustered with IC2 (n = 54) with one major subtype comprising isolates from 12 hospitals in the three countries, which included 19 XDR and 16 PDR isolates.ConclusionsCarbapenem resistance rates were very high in A. baumannii recovered from patients with VAP. Almost half of the isolates were colistin resistant, and 42 (64.6%) isolates were XDR or PDR. Rep-PCR confirmed IC2 is the predominant clonal lineage in Europe and suggests the presence of an epidemic XDR/PDR A. baumannii clone that has spread in Greece, Italy and Spain. These data highlight the difficulty in empirical treatment of patients with A. baumannii VAP in centres with a high prevalence of carbapenem-resistant A. baumannii.

Tigecycline combination for ventilator-associated pneumonia caused by extensive drug-resistant Acinetobacter baumannii.

Extensive drug-resistant Acinetobacter baumannii (XDR A. baumannii) has emerged as an important pathogen in patients with ventilator-associated pneumonia (VAP) worldwide. This study determined whether or not combination tigecycline (TGC) treatment improved the short-term outcome of patients with XDR A. baumannii-induced VAP. Methods: Fifty-eight patients admitted to our intensive care unit (ICU) with confirmed XDR A. baumannii VAP between January 2011 and June 2013 were retrospectively studied. Fourteen patients were excluded. The included subjects were classified into two groups depending on treatment regimens with or without TGC (TGC group, n=20; non-TGC group, n=24). Thirty-day mortality rates, and clinical and microbiologic responses were reviewed and compared in detail. Microbiological eradication was observed in 3 patients (15.0%) in the TGC group and 7 patients (29.2%) in the non-TGC group (P=0.264). The mean time-to-eradication of XDR A. baumannii was 5.3±2.1 versus 7.6±4.0 days (P=0.395). Ten of 20 (50%) patients developed resistance to TGC after initiation of TGC therapy in the TGC group. Clinical cure were achieved in 50.0% of the patients (10/20) in the TGC group and 45.8% of the patients (7/24) in the non-TGC group (P=1.000). No differences existed in the 30-day mortality, length of ICU stay, length of hospital stay (LOS), and length of invasive mechanical ventilation (MV) between the two groups. The occurrence of septic shock was significantly lower in the TGC group (20.0% vs. 54.2%; P=0.030). TGC combination therapy did not improve the clinical cure and microbiologic eradication in patients with XDR A. baumannii VAP. TGC combination therapy did not decrease all-cause mortality in patients with XDR A. baumannii VAP. TGC combination therapy reduced the incidence of septic shock in patients with XDR A. baumannii VAP, and might decrease the incidence of poly-microbial VAP. TGC combination therapy can only be recommended as an option when other optimized therapeutics, such as colistin, are unavailable.

Breath analysis for noninvasively differentiating Acinetobacter baumannii ventilator-associated pneumonia from its respiratory tract colonization of ventilated patients

A number of multiresistant pathogens including Acinetobacter baumannii (A. baumannii) place a heavy burden on ventilator-associated pneumonia (VAP) patients in intensive care units (ICU). It is critically important to differentiate between bacterial infection and colonization to avoid prescribing unnecessary antibiotics. Quantitative culture of lower respiratory tract (LRT) specimens, however, requires invasive procedures. Nowadays, volatile organic compounds (VOCs) have been studied in vitro and in vivo to identify pathogen-derived biomarkers. Therefore, an exploratory pilot study was conceived for a proof of concept that the appearance and level of A. baumannii-derived metabolites might be correlated with the presence of the pathogen and its ecological niche (i.e. the infection and colonization states) in ICU ventilated patients.Twenty patients with A. baumannii VAP (infection group), 20 ventilated patients with LRT A. baumannii colonization (colonization group) and 20 ventilated patients with neurological disorders, but without pneumonia or A. baumannii colonization (control group) were enrolled in the in vivo pilot study. A clinical isolate of A. baumannii strains was used for the in vitro culture experiment. The adsorptive preconcentration (solid-phase microextraction fiber and Tenax® TA) and analysis technique of gas chromatography–mass spectrometry were applied in the studies.Breath profiles could be visually differentiated between A. baumannii cultivation in vitro and culture medium, and among in vivo groups. In the in vitro experiment, nine compounds of interest (2,5-dimethyl-pyrazine, 1-undecene, isopentyl 3-methylbutanoate, decanal, 1,3-naphthalenediol, longifolene, tetradecane, iminodibenzyl and 3-methyl-indene) in the headspace were found to be possible A. baumannii derivations. While there were eight target VOCs (1-undecene, nonanal, decanal, 2,6,10-trimethyl-dodecane, 5-methyl-5-propyl-nonane, longifolene, tetradecane and 2-butyl-1-octanol) exhibiting characteristics of A. baumannii VAP derivations. The selected VOC profile in vivo could be adopted to efficiently differentiate the presence of LRT A. baumannii from its absence, and LRT A. baumannii infection from its colonization (AUC = 0.89 and 0.88, respectively).It is not feasible to simply transfer the metabolic biomarkers from the in vitro condition to in vivo. The direct detection of exhaled A. baumannii-derived VOCs may be adopted for an early alert of the LRT bacterial presence in ventilated ICU patients, and even in different parasitic states of A. baumannii (i.e. infection and colonization). However, further refinement and validation are required before its clinical use.

Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23%vs 15%, P=.01 and 34%vs. 15%, P<.001 in propensity score-matched subgroups). Administration of antifungal agents was not associated with A. baumannii VAP (29%vs. 21%, P=.153) but with higher in-hospital mortality (53%vs. 39%, P=.037). Candida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP.

Repeated local emergence of carbapenem-resistant Acinetobacter baumannii in a single hospital ward

We recently reported a dramatic increase in the prevalence of carbapenem-resistant Acinetobacter baumannii infections in the intensive care unit (ICU) of a Vietnamese hospital. This upsurge was associated with a specific oxa23-positive clone that was identified by multilocus VNTR analysis. Here, we used whole-genome sequence analysis to dissect the emergence of carbapenem-resistant A. baumannii causing ventilator-associated pneumonia (VAP) in the ICU during 2009–2012. To provide historical context and distinguish microevolution from strain introduction, we compared these genomes with those of A. baumannii asymptomatic carriage and VAP isolates from this same ICU collected during 2003–2007. We identified diverse lineages co-circulating over many years. Carbapenem resistance was associated with the presence of oxa23, oxa40, oxa58 and ndm1 genes in multiple lineages. The majority of resistant isolates were oxa23-positive global clone GC2; fine-scale phylogenomic analysis revealed five distinct GC2 sublineages within the ICU that had evolved locally via independent chromosomal insertions of oxa23 transposons. The increase in infections caused by carbapenem-resistant A. baumannii was associated with transposon-mediated transmission of a carbapenemase gene, rather than clonal expansion or spread of a carbapenemase-harbouring plasmid. Additionally, we found evidence of homologous recombination creating diversity within the local GC2 population, including several events resulting in replacement of the capsule locus. We identified likely donors of the imported capsule locus sequences amongst the A. baumannii isolated on the same ward, suggesting that diversification was largely facilitated via reassortment and sharing of genetic material within the localized A. baumannii population.

Treatment of Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia

Carbapenem-resistant Acinetobacter baumannii has been increasingly reported as the causative agent of ventilator-associated pneumonia (VAP) among patients in the intensive care units. However, there are insufficient data to guide the appropriate treatment for such infection. Our aim was to compare the outcome of carbapenem-resistant A. baumannii VAP treated with colistin or with ampicillin-sulbactam. We conducted a retrospective study of patients diagnosed with carbapenem-resistant A. baumannii VAP during 2008 and 2009. Clinical and microbiologic cure rates, 30-day mortality, and change in renal function were compared between patients treated with colistin versus those treated with ampicillin-sulbactam. The association between treatment and mortality was examined through multivariable logistic regression analysis. Of the 98 patients diagnosed with carbapenem-resistant A. baumannii VAP, 66 were treated with colistin and 32 with ampicillin-sulbactam. Baseline characteristics of patients were similar, except for a longer intensive care unit stay and lower creatinine clearance test before VAP diagnosis among patients treated with colistin. Clinical cure rates were similar in the 2 groups. In the colistin group, microbiologic failure rates were higher at 7 days [16/33 (48%) vs. 3/17 (18%); P = 0.03]; patients had a more significant elevation in creatinine (+0.2 ± 1.0 mg/dL vs. -0.3 ± 1.1 mg/dL; P = 0.021), and treatment was associated with an increased 30-day mortality (adjusted-odds ratio, 6.5; 95% confidence interval, 1.348-31.342; P = 0.02). In conclusion, patients treated with colistin or ampicillin-sulbactam had similar clinical cure rates. However, colistin was associated with higher rates of microbiologic failure, reduction in renal function, and an increased 30-day mortality. A prospective study comparing high-dose colistin and ampicillin-sulbactam for the treatment of carbapenem-resistant A. baumannii VAP is warranted.

The efficiency of routine endotracheal aspirate cultures compared to bronchoalveolar lavage cultures in ventilator-associated pneumonia diagnosis.

Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in İntensive Care Units (ICUs) and its mortality rate varies from 24% to 50%. The most important factor in decreasing the mortality is administering adequate antibiotics as early as possible. In this study, we investigate the efficiency of routine endotracheal aspirate (EA) cultures to identify the etiology of VAP earlier. Fifty-nine patients who were accepted to our ICU with acute cerebrovascular disease with mechanical ventilation (MV) requirement were chosen for this study over a 12-month period. The patients intubated in our ICU were included in the study to exclude prior colonization. Upon ICU admission, the patient's; age, sex, comorbidities, diagnosis, acute physiology and chronic health evaluation II score, and sequential organ failure assessment (SOFA) score were recorded. When bronchoalveolar lavage (BAL) was performed, the SOFA score, temperature, leukocyte count, C-reactive protein levels, PaO2/FiO2ratio, PCO2, clinical pulmonary infection score value, length of MV, and presence of antimicrobiological treatments were recorded. Routine microbiological analysis was performed by EA (pre-VAP EA) twice weekly in all patients until the endotracheal tube was removed. When VAP was suspected, fiberoptic bronchoscopy examination with BAL was performed. A diagnosis of VAP was established when the BAL quantitative culture grew at least one microorganism at a concentration ≥104 cfu/mL. VAP was diagnosed in 41 (69%) of the 59 patients based on BAL culture results. Among 41 positive BAL cultures, pre-VAP EA identified the same microorganism with the same antibiotics resistance pattern in 23 (56%) patients. Regarding only late-onset VAP, pre-VAP EA identified the same microorganisms found by BAL culture in 17 (63%) of the 27 cases. Among 18 BAL culture negative patients, 7 (39%) patients had negative prior pre-VAP EA culture results. Acinetobacter baumannii was the most frequently isolated microorganism from BAL cultures (n = 21, 51%). The diagnostic value of pre-VAP EA results in predicting A. baumannii VAP documented with the following values (sensitivity: 62%; specificity: 95%, positive predictive value: 87%, negative predictive value: 82%). VAP patients should be treated with international guidelines, but if pre-VAP EA cultures identify multidrug resistant pathogens, the initial antibiotic therapy should cover these microorganisms. Thus, quantitative EA cultures are a useful noninvasive diagnostic tool in critically ill patients suspected of having pneumonia especially in the case of VAP.

National Survey of Thai Infectious Disease Physicians on Treatment of Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia: The Role of Infection Control Awareness.

OBJECTIVE To evaluate the expected and treatment outcomes of Thai infectious disease physicians (IDPs) regarding carbapenem-resistant Acinetobacter baumannii (CRAB) ventilator-associated pneumonia (VAP) METHODS From June 1, 2014, to March 1, 2015, survey data regarding the expected and clinical success rates of CRAB VAP treatment were collected from all Thai IDPs. The expected success rate was defined as the expectation of clinical response after CRAB VAP treatment for the given case scenario. Clinical success rate was defined as the overall reported success rate of CRAB VAP treatment based on the clinical practice of each IDP. The expected and clinical success rates were divided into low (80%) categories and were then compared with standard clinical response rates archived in the existing literature. RESULTS Of 183 total Thai IDPs, 111 (60%) were enrolled in this study. The median expected and clinical success rates were 68% and 58%, respectively. Using multivariate analysis, we determined that working in a hospital that implemented the standard intervention combined with an intensified infection control (IC) intervention for CRAB (adjusted odds ratio [aOR], 3.01; 95% confidence interval [CI], 1.17-7.73; P=.02) was associated with standard and high expected rates (>60%). Being a board-certified IDP (aOR, 5.76; 95% CI, 2.16-15.37; P60%). We identified a significant correlation between expected and clinical success rates (r=0.58; P<.001). CONCLUSIONS Awareness of IC among IDPs can improve physicians' expected and clinical success rates for CRAB VAP treatment, and treatment experience impacts overall treatment success. Infect. Control Hosp. Epidemiol. 2015;37(1):61-69.

Spread of multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa clones in patients with ventilator-associated pneumonia in an adult intensive care unit at a university hospital

BackgroundIn Brazil, ventilator-associated pneumonia (VAP) caused by carbapenem resistant Acinetobacter baumannii and Pseudomonas aeruginosa isolates are associated with significant mortality, morbidity and costs. Studies on the clonal relatedness of these isolates could lay the foundation for effective infection prevention and control programs. ObjectivesWe sought to study the epidemiological and molecular characteristics of A. baumannii vs. P. aeruginosa VAP in an adult intensive care unit (ICU). MethodsIt was conducted a cohort study of patients with VAP caused by carbapenem resistant A. baumannii and P. aeruginosa during 14 months in an adult ICU. Genomic studies were used to investigate the clonal relatedness of carbapenem resistant OXA-23-producing A. baumannii and P. aeruginosa clinical isolates. The risk factors for acquisition of VAP were also evaluated. Clinical isolates were collected for analysis as were samples from the environment and were typed using pulsed field gel electrophoresis. ResultsMultivariate logistic regression analysis identified trauma diagnosed at admission and inappropriate antimicrobial therapy as independent variables associated with the development of A. baumannii VAP and hemodialysis as independent variable associated with P. aeruginosa VAP. All carbapenem resistant clinical and environmental isolates of A. baumannii were OXA-23 producers. No MBL-producer P. aeruginosa was detected. Molecular typing revealed a polyclonal pattern; however, clone A (clinical) and H (surface) were the most frequent among isolates of A. baumannii tested, with a greater pattern of resistance than other isolates. In P. aeruginosa the most frequent clone I was multi-sensitive. ConclusionThese findings suggest the requirement of constant monitoring of these microorganisms in order to control the spread of these clones in the hospital environment.

Risk factors of multidrug-resistant, extensively drug-resistant and pandrug-resistant Acinetobacter baumannii ventilator-associated pneumonia in a Medical Intensive Care Unit of University Hospital in Thailand.

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii remains a significant cause of morbidity and mortality. Increasing antimicrobial resistance influences the selection of antibiotic treatment especially pandrug-resistant A.baumannii. A retrospective cohort study was conducted in the Medical Intensive Care Unit to identify the risk factors of VAP caused by multidrug-resistant A.baumannii (MDR-AB), extensively drug-resistant A.baumannii (XDR-AB) and pandrug-resistant A.baumannii (PDR-AB). All 337 adult patients with confirmed A.baumannii VAP were included. The incidence of MDR-AB, XDR-AB and PDR-AB were 72 (21.4%), 220 (65.3%) and 12 (3.6%), respectively. The risk factor for MDR-AB was prior use of carbapenems (OR 5.20; 95% CI 1.41-19.17). Risk factors for XDR-AB were the prior use of carbapenems (OR, 6.30; 95% CI, 1.80-21.97) and a high Sequential Organ Failure Assessment (SOFA) score (OR 1.35; 95% CI 1.07-1.71). In PDR-AB, the risk factors were the prior use of colistin (OR, 155.95; 95% CI, 8.00-3041.98), carbapenems (OR, 12.84; 95% CI, 1.60-103.20) and a high Simplified Acute Physiology Score (SAPS II) (OR 1.10; 95% CI 1.01-1.22). In conclusion, previous exposure to antibiotics and severity of VAP were risk factors of drug-resistant A. baumannii. Judicious use of carbapenems and colistin is recommended to prevent the antimicrobial-resistant strains of this organism.

Acinetobacter baumannii ventilator-associated pneumonia: epidemiology, clinical characteristics, and prognosis factors

The aim of this study was to describe the epidemiological characteristics of Acinetobacter baumannii ventilator-associated pneumonia (VAP) and to identify factors predictive of a poor outcome. A retrospective study was conducted over 16 months in a Tunisian intensive care unit (ICU). All adult patients with A. baumannii VAP were included. Ninety-two patients were included in they study; 41 (44.6%) were admitted because of multiple trauma. The mean age of the patients was 44.5±19.5 years. All patients needed mechanical ventilation on admission. The mean SAPS II score was 39±15. The mean delay before VAP onset was 8.1±4.7 days. On VAP onset, 57 patients (62%) developed septic shock. Only 14.2% of isolated strains were susceptible to imipenem; none were resistant to colistin. The mean duration of mechanical ventilation was 20±11 days. The mean duration of ICU stay was 24.3±18.7 days. ICU mortality was 60.9%. In the multivariate analysis, factors predictive of a poor outcome were previously known hypertension (odds ratio 5.8, 95% confidence interval 1.4-24.9; p=0.018) and VAP-related septic shock (odds ratio 8.5, 95% confidence interval 3-23.7; p<0.001). A. baumannii VAP is associated with a high mortality. Hemodynamic impairment is predictive of a poor outcome.

Use of high-dose IV and aerosolized colistin for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia: do we really need this treatment?

In this study we aimed to assess the safety and efficacy of high-dose IV colistin (COL) and aerosolized COL for the treatment of Acinetobacter baumannii ventilator-associated pneumonia (VAP). Critically ill adult patients who received IV COL for multidrug-resistant A. baumannii VAP were evaluated retrospectively. A total of 45 patients were evaluated [15 patients with high-dose COL (2.5mg/kg every 6h), 20 patients with normal dose (2.5mg/kg every 12h), and 10 patients with low dose, determined according to creatine clearance]. Aerosolized COL was used in 29 patients treated with parenteral COL and 16 patients received only parenteral COL. The clinical response rates on the fifth day were 50, 30, and 27% with the normal, low, and high doses, respectively. However, the clinical response rates at the end of the therapy had declined to 30, 30, and 7% with the normal, low, and high doses, respectively. The bacteriological clearance rates at the end of the therapy were 65, 75, and 64%, with the normal, low, and high doses, respectively. With the aerosolized COL, the clinical response rates on the fifth day and at the end of the therapy were 35 and 14%, whereas these rates were 44 and 38% without the aerosolized COL. Bacteriological clearance rates with and without the aerosolized COL were 76 and 69%, respectively. The nephrotoxicity rate was 40% for the high-dose COL, whereas it was 35% for the normal dose, and 20% for the low-dose COL. In conclusion, higher doses of COL and aerosolized COL had no advantages over lower doses in alleviating multidrug-resistant A. baumannii VAP. Moreover, the higher doses and the aerosolized COL increased the nephrotoxicity risk and seemed not to be safe.

Mortality risk factors in patients with Acinetobacter baumannii ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP. We retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group. Compared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7mmol/L, respiratory rate >30/min, low blood pressure (systolic <90mmHg or diastolic <60mmHg), age >65 years (CURB-65)≥3, creatinine>1.6mg/dL, C-reactive protein≥100mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count <4/μL or >1.1×10(4)/μL, and higher hospital mortality rates. Inadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB≥3 and C-reactive protein≥120mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count <4/μL or >1.1×10(4)/μL were independent risk factors for carbapenem resistance.

Outcome of ventilator-associated pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa treated with aerosolized colistin in neonates: a retrospective chart review

Multidrug-resistant (MDR) gram-negative bacteria-related nosocomial infections and ventilator-associated pneumonia (VAP) presents an emerging challenge to clinicians. Older antimicrobial agents such as colistin have become life-saving drugs because of the susceptibility of these pathogens. We report our experience with aerosolized colistin in two preterm and one term neonate with Acinetobacter baumannii and Pseudomonas aeruginosa-related VAP who were unresponsiveness to previous antimicrobial treatment. All pathogens were isolated from tracheal aspirate. We used 5 mg/kg (base activity) aerosolized colistin methanesulfonate sodium in every 12 h as an adjunctive therapy for VAP. VAP was treated by 14, 14, and 16-day courses of aerosolized colistin in these patients, respectively. No adverse effect such as nephrotoxicity or neurotoxicity was observed. We found that aerosolized colistin was tolerable and safe, and it may be an adjunctive treatment option for MDR gram-negative bacterial VAP in neonates. Further studies are needed to determine appropriate doses for aerosolized colistin and its eligibility as an alternative treatment choice in newborns.

Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia

To compare the safety and efficacy of ampicillin/sulbactam (Amp/Sulb) and colistin (COL) in the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP). A prospective cohort study in adult critically ill patients with VAP. Patients were randomly assigned to receive Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously. Dosage was adjusted according to creatinine clearance. A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb). Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13), respectively. The difference was not statistically significant. Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups, respectively (p<0.2). Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS). Colistin and high-dose ampicillin/sulbactam were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP.