XDR-AB Infections Research Articles

Risk factors and predictive model for nosocomial infections by extensively drug-resistant Acinetobacter baumannii.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a significant pathogen in hospital environments, particularly in intensive care units (ICUs). XDRAB's resistance to conventional antimicrobial treatments and ability to survive on various surfaces pose a substantial threat to patient health, often resulting in severe infections such as ventilator-associated pneumonia (VAP) and bloodstream infections (BSI). We retrospectively analyzed clinical data from 559 patients with XDRAB infections admitted to Jinhua Central Hospital between January 2021 and December 2023. Patients were randomly divided into a training set (391 cases) and a testing set (168 cases). Variables were selected using Lasso regression and logistic regression analysis, and a predictive model was constructed and validated internally and externally. Model performance and clinical utility were evaluated using the Hosmer-Lemeshow test, C-index, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC). Lasso regression analysis was used to screen 35 variables, selecting features through 10-fold cross-validation. We chose lambda.1se=0.03450 (log(lambda.1se)=-3.367), including 10 non-zero coefficient features. These features were then included in a multivariate logistic regression analysis, identifying 8 independent risk factors for XDRAB infection: ICU stay of 1-7 days (OR=3.970, 95%CI=1.586-9.937), ICU stay >7 days (OR=12.316, 95%CI=5.661-26.793), hypoproteinemia (OR=3.249, 95%CI=1.679-6.291), glucocorticoid use (OR=2.371, 95%CI=1.231-4.564), urinary catheterization (OR=2.148, 95%CI=1.120-4.120), mechanical ventilation (OR=2.737, 95%CI=1.367-5.482), diabetes mellitus (OR=2.435, 95%CI=1.050-5.646), carbapenem use (OR=6.649, 95%CI=2.321-19.048), and β-lactamase inhibitor use (OR=4.146, 95%CI=2.145-8.014). These 8 factors were used to construct a predictive model visualized through a nomogram. The model validation showed a C-index of 0.932 for the training set and 0.929 for the testing set, with a Hosmer-Lemeshow test p-value of 0.47, indicating good calibration. Furthermore, the DCA curve demonstrated good clinical decision-making performance, and the CIC curve confirmed the model's reliable clinical impact. Regression analysis identified ICU stay duration, hypoproteinemia, glucocorticoid use, urinary catheterization, mechanical ventilation, diabetes mellitus, carbapenem use, and β-lactamase inhibitor use as independent risk factors for XDRAB infection. The corresponding predictive model demonstrated high accuracy and stability.

A retrospective study of the efficacy of sulbactam in the treatment of patients with extensively drug-resistant Acinetobacter baumannii infections.

Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6g/day), for XDR-AB infection. A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. The formulation of SBT in our study is 0.5g per vial. Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with the dose of SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a shorter time to clinical response. No adverse effects related were reported. The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.

A systematic review and meta-analysis for risk factor profiles in patients with resistant Acinetobacter baumannii infection relative to control patients.

Acinetobacter baumannii is a major cause of nosocomial infections and high mortality rates. Evaluation of risk factors for such resistant infections may aid surveillance and diagnostic initiatives, as well as, can be crucial in early and appropriate antibiotic therapy. To identify the risk factors in patients with resistant A. baumannii infection with respect to controls. Prospective or retrospective cohort and case-control studies reporting the risk factors for resistant A. baumannii infection were collected through two data sources, MEDLINE/PubMed and OVID/Embase. Studies published in the English language were included while animal studies were excluded. The Newcastle-Ottawa Scale was used to assess the quality of studies. The odds ratio of developing antibiotic resistance in patients with A. baumannii infection was pooled using a random-effect model. The results are based on 38 studies with 60878 participants (6394 cases and 54484 controls). A total of 28, 14, 25, and 11 risk factors were identified for multi-drug resistant (MDRAB), extensive-drug resistant (XDRAB), carbapenem-resistant (CRAB) and imipenem resistant A. baumannii infection (IRAB), respectively. In the MDRAB infection group, exposure to carbapenem (OR 5.51; 95% CI: 3.88-7.81) and tracheostomy (OR 5.01; 95% CI: 2.12-11.84) were identified with maximal pool odd's ratio. While previous use of amikacin (OR 4.94; 95% CI: 1.89-12.90) and exposure to carbapenem (OR 4.91; 95% CI: 2.65-9.10) were the foremost factors associated with developing CRAB infection. Further analysis revealed, mechanical ventilation (OR 7.21; 95% CI: 3.79-13.71) and ICU stay (OR 5.88; 95% CI: 3.27-10.57) as the most significant factors for XDRAB infection. The exposure of carbapenem, amikacin (previous) and mechanical ventilation were the most significant risk factors for multidrug, extensive-drug, and carbapenem resistance in patients with A. baumannii infection respectively. These findings may guide to control and prevent resistant infections by identifying the patients at higher risk of developing resistance.

Clinical Epidemiology, Treatment, and Prognostic Factors of Hospital-Acquired Pneumonia Caused by the Extensively Drug-Resistant Acinetobacter Baumannii

Extensively drug-resistant Acinetobacter baumannii (XDRAB) can acquire drug resistance genes, which are rapidly cloned and transmitted, leading to worldwide spread and posing significant treatment challenges. This study aimed to clarify effective treatment methods during XDRAB infection and factors affecting patient prognosis. Clinical features, treatment, and prognosis of 65 patients with hospital-acquired XDRAB pneumonia clinically diagnosed at Guangzhou First People's Hospital between January 2019 and December 2020 were retrospectively analyzed. Of 65 subjects, only 37 survived. There was no significant difference in anti-A. baumannii activity according to type or combination of antibiotics administered between patients that survived and those that died (p > 0.05). The use of antibacterial drugs during infection did not effectively improve clinical outcomes. Advanced age, multiple organ failure, and disease severity were significantly negatively correlated while effective airway management was positively associated with bacterial clearance (p < 0.05). In multivariate analysis, age and APACHE score were independent risk factors affecting prognosis. Tracheotomy during infection was a protective factor contributing to survival (p < 0.05). Advanced age and disease severity independently affected patient prognosis, while use and type of antibacterial treatment did not substantially affect the prognosis. Advanced age and severe disease are independent risk factors that affect patient prognosis. Timely and effective airway management is key to improving the prognosis of patients with hospital-acquired XDRAB infection.

A descriptive case series of pharmacokinetic/pharmacodynamic target attainment and microbiological outcome in critically ill patients with documented severe extensively drug-resistant Acinetobacter baumannii bloodstream infection and/or ventilator-associated pneumonia treated with cefiderocol

The aim of this study was to explore the relationship between cefiderocol pharmacokinetic/pharmacodynamic (PK/PD) target attainment and microbiological outcome in critically ill patients affected by extensively drug-resistant Acinetobacter baumannii (XDR-AB) bloodstream infection (BSI) and/or ventilator-associated pneumonia (VAP). Patients who received compassionate use of cefiderocol to treat documented XDR-AB infections at the intensive care unit of the IRCCS Azienda Ospedaliero-Universitaria of Bologna and who underwent therapeutic drug monitoring (TDM) from 15 March 2021 to 30 April 2021 were retrospectively assessed. Cefiderocol trough concentration (Cmin) was determined at steady-state, and the free fraction (fCmin) was calculated according to a plasma protein binding of 58%. The fCmin/MIC ratio was selected as a pharmacodynamic parameter of cefiderocol efficacy and was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The association between fCmin/MIC and microbiological outcome was assessed. A total of 13 patients treated with cefiderocol for the management of XDR-AB infections (6 BSI plus VAP, 5 VAP and 2 BSI) were retrieved. fCmin/MIC ratios were suboptimal in 3 cases (23%) and quasi-optimal or optimal in 5 cases each (38%). Microbiological failure occurred in seven cases (54%; six with VAP and one with VAP plus BSI). Microbiological failure occurred in 80% of patients with suboptimal fCmin/MIC compared with 29% of those achieving optimal or quasi-optimal fCmin/MIC ratio. Suboptimal attainment of PK/PD targets of cefiderocol may lead to microbiological failure of treatment with cefiderocol of critically ill patients affected by XDR-AB VAP.

High-Dose versus Standard-Dose Tigecycline Treatment of Secondary Bloodstream Infections Caused by Extensively Drug-Resistant Acinetobacter baumannii: An Observational Cohort Study.

BackgroundExtensively drug-resistant Acinetobacter baumannii (XDR-AB) infections have become difficult to treat and are associated with a high mortality rate. Tigecycline is one of the most effective agents used to treat XDR-AB infections, but data from treating bloodstream infection (BSI) in standard dose do not look promising, because of its low plasma concentration. Secondary BSI with primary infection source may indicate tigecycline treatment with a higher dose. Currently, little is known about the application of high-dose tigecycline among patients with secondary BSI caused by XDR-AB. We aimed to investigate the outcomes for high-dose (HD) tigecycline treatment versus standard-dose (SD) treatment of these patients.MethodsAn observational cohort study was conducted at four university affiliated hospitals in mainland China. Adult inpatients who were confirmed as having secondary BSI caused by XDR-AB and received definitive tigecycline treatment were consecutively included. Patients who were treated with 50 mg every 12 h were defined as the SD group, and a twice dose was defined as the HD group.ResultsOf the enrolled patients, 63 received SD and 88 received HD tigecycline treatment. Patients in the two groups had similar with regard to baseline clinical conditions. The 30-day survival was affected by the source of the primary infection. Survival was significantly better in patients with non-pulmonary-infection-related BSI than in patients with pulmonary-infection-related BSI. Multivariate Cox regression confirmed that HD had a protective effect only observed in patients with non-pneumonia-related BSI.ConclusionA tigecycline dose that is twice its standard dose is better for the treatment of XDR-AB infection only in BSI associated with non-pulmonary infection.

Epidemiology and clinical outcomes associated with extensively drug-resistant (XDR) Acinetobacter in US Veterans' Affairs (VA) medical centers.

Although infections caused by Acinetobacter baumannii are often healthcare-acquired, difficult to treat, and associated with high mortality, epidemiologic data for this organism are limited. We describe the epidemiology, clinical characteristics, and outcomes for patients with extensively drug-resistant Acinetobacter baumannii (XDRAB). Retrospective cohort study. Department of Veterans' Affairs Medical Centers (VAMCs). Patients with XDRAB cultures (defined as nonsusceptible to at least 1 agent in all but 2 or fewer classes) at VAMCs between 2012 and 2018. Microbiology and clinical data was extracted from national VA datasets. We used descriptive statistics to summarize patient characteristics and outcomes and bivariate analyses to compare outcomes by culture source. Among 11,546 patients with 15,364 A. baumannii cultures, 408 (3.5%) patients had 667 (4.3%) XDRAB cultures. Patients with XDRAB were older (mean age, 68 years; SD, 12.2) with median Charlson index 3 (interquartile range, 1-5). Respiratory specimens (n = 244, 36.6%) and urine samples (n = 187, 28%) were the most frequent sources; the greatest proportion of patients were from the South (n = 162, 39.7%). Most patients had had antibiotic exposures (n = 362, 88.7%) and hospital or long-term care admissions (n = 331, 81%) in the prior 90 days. Polymyxins, tigecycline, and minocycline demonstrated the highest susceptibility. Also, 30-day mortality (n = 96, 23.5%) and 1-year mortality (n = 199, 48.8%) were high, with significantly higher mortality in patients with blood cultures. The proportion of Acinetobacter baumannii in the VA that was XDR was low, but treatment options are extremely limited and clinical outcomes were poor. Prevention of healthcare-associated XDRAB infection should remain a priority, and novel antibiotics for XDRAB treatment are urgently needed.

Near-infrared-excited upconversion photodynamic therapy of extensively drug-resistant Acinetobacter baumannii based on lanthanide nanoparticles.

Extensively drug-resistant Acinetobacter baumannii (XDR-AB) has raised considerable concerns due to its mortal damage to humans and its high transmission rate of infections in hospitals. However, current antibiotics not only show poor anti-infection effects in vivo but also frequently cause high nephrotoxicity and neurotoxicity. Herein, we report a near-infrared (NIR) light-initiated antimicrobial photodynamic therapy (aPDT) to effectively treat in vivo XDR-AB infections based on photosensitizer (PS) loaded upconversion nanoparticles (UCNPs, LiYF4:Yb/Er). Such nanoagents feature robust NIR triggered UC luminescence and high-efficiency energy transfer from UCNPs to the loaded PS, thereby allowing NIR-triggered generation of reactive oxygen species (ROS) for destroying the bacterial cell membrane. This strategy permits a high antibacterial activity against XDR-AB, resulting in a decline of 4.72 log10 in viability at a dose of 50 μg mL-1 UCNPs-PVP-RB with 980 nm laser irradiation (1 W cm-2). More significantly, we can achieve excellent therapeutic efficacy against deep-tissue (about 5 mm) XDR-AB infections without causing any side effects in the murine model. In brief, such NIR-activated aPDT may open up new avenues for treating various deep-tissue intractable infections.

Efficacy of φkm18p phage therapy in a murine model of extensively drug-resistant Acinetobacter baumannii infection.

PurposeFew effective antibiotics are available for treating extensively drug-resistant Acinetobacter baumannii (XDRAB) sepsis. Phage therapy may show potential in treating XDRAB infections.Materials and methodsWe studied φkm18p phage therapy in BALB/c and C57BL/6 mice models of XDRAB bacteremia.ResultsWe observed survival rates of nearly 100% in groups given phage therapy concurrent with XDRAB at different multiplicities of infection. In mice that received phage therapy after a 1-hour delay, the survival rate decreased to about 50%. The bacterial load in the blood decreased from 108 to 102 and 103 colony-forming units (CFU)/mL in the concurrent treatment group. In the phage therapy group, the levels of the cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), were low at 3 hours after infection. Although some phage-resistant mutants were isolated after phage therapy, a cytotoxicity study showed that they had reduced fitness.ConclusionPhage therapy in XDRAB bacteremia increased the animal survival rates, decreased the bacteremia loads, and decreased the levels of inflammatory markers TNF-α and IL-6. However, the reduced therapeutic effect with delayed administrations may be a concern in developing a successful phage therapy for treating acute infections of multidrug-resistant pathogens.

Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis

To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection. We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events. A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections. Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Clinical outcomes and nephrotoxicity of colistin loading dose for treatment of extensively drug-resistant Acinetobacter baumannii in cancer patients.

BackgroundColistin is a last-line defense therapy against extensively drug-resistant Acinetobacter baumannii (XDR-AB). Despite a loading dose of colistin being applied in many clinical practices, studies evaluating the effect of the loading dose of colistin in cancer patients remain limited.Patients and methodsA retrospective cohort study of cancer patients who received either a loading or non-loading dose of colistin for treatment of XDR-AB was conducted. For each group, the clinical response, bacteriological eradication and serum creatinine were recorded. Logistic regression was applied to evaluate the effects of therapy on each of the three aforementioned outcomes.ResultsOne hundred and two patients diagnosed with XDR-AB infections between January 2012 and December 2015 were recruited. Only 75 patients were given a loading dose of colistin. There was no significant clinical and microbiological response in patients in the loading dose group or patients in the non-loading dose group. However, 38 (50.67%) patients in the loading dose group and 6 (22.22%) patients in the non-loading dose group developed nephrotoxicity according to the RIFLE criteria (p = 0.013). Multivariate logistic regression analysis showed that independent predictors of clinical response were Charlson score ≥4 and duration of colistin treatment ≥10 days. Septic shock correlated with both poor clinical and microbiological response. Independent predictors for nephrotoxicity were loading dose colistin and patient’s age ≥60 years.ConclusionAdministration of colistin loading dose did not significantly increase clinical response, microbiological response or mortality rate compared to non-loading dose in cancer patients with XDR-AB-related infections. However, nephrotoxicity was significantly higher when patients received loading dose colistin.

Colistin monotherapy versus colistin-based combination therapy in the treatment of extensive drug-resistant Acinetobacter baumannii infections: A retrospective cohort study

Introduction: Acinetobacter baumannii is a Gram-negative Coccobacillus and is a frequent cause of hospital-acquired infections. Because some strains of A. baumannii are resistant to many antibiotics (i.e., extensively drug-resistant A. baumannii, or XDRAB), selecting antibiotics to treat infected patients is challenging. Clinical outcomes in critically ill patients with XDRAB infections are poor. In this study, we evaluated the clinical effectiveness of colistin as monotherapy and in combination with other antibiotics. Patients and Methods: A retrospective cohort study was performed on 94 critically ill patients (age ≥18 years) to assess the clinical effectiveness of treating XDRAB infections with colistin, either in monotherapy or combination with tigecycline, meropenem, or both. Clinical and microbiological data were obtained from patient records. We included patients suffering from XDRAB ventilation-associated pneumonia (VAP), or ventilator-associated tracheobronchitis (VAT), or VAT with bacteremia. Results: The mean age of the patients was 53.3 years (±23.7 years), and the mean Acute Physiology and Chronic Health Evaluation II score was 22.7 (standard deviation = 7.1). VAP and VAT with bacteremia were found in 84% and 16% of patients, respectively. Half (51%) of patients achieved microbiological clearance. The median Intensive Care Unit (ICU) stay was 29 days (interquartile range [IQR]: 17, 55) and the median mechanical ventilation (MV) duration was 21 days (IQR: 12, 42). MV duration and ICU length of stay were lower in the group of patients treated with colistin and meropenem than in those treated with colistin alone. Mortality was significantly lower in patients who received (colistin and tigecycline 30%) than in those who were treated with monotherapy (75%) with an odd ratio 0.03 (95% confidence interval: 0.00, 0.32; P

&amp;lt;i&amp;gt;In Vitro&amp;lt;/i&amp;gt; Activity of Colistin and Vancomycin or Azithromycin Combinations on Extensively Drug Resistant &amp;lt;i&amp;gt;Acinetobacter baumannii&amp;lt;/i&amp;gt; Clinical Isolates

Background: Extensively drug resistant Acinetobacter baumannii (XDR-AB) presents an increasing challenge to health care in Egypt as they are among the most common bacteria isolated in hospital setting. Treatment of such infections usually involves the use of antimicrobial agents in combination. Various combinations have been proposed, with colistin serving as the backbone in many of them even for colistin resistant isolates. Aim: The study was conducted in order to test the in vitro combined effects of colistin and vancomycin or azithromycin against (XDR-AB) causing infections at Alexandria Main University Hospital in Egypt, in an attempt to detect the possibility of a beneficial combination therapy. Material/Methods: Thirty XDR-AB clinical isolates were included in the study. Antibiotic susceptibility testing was performed using automated Vitek 2 compact system and disc diffusion method. Colistin antibiotic disc diffusion test was compared with broth microdilution method. Organisms were also tested against colistin and vancomycin or azithromycin in combination using checkerboard synergy test and FICI (Fractional Inhibitory Concentration Index) was calculated. Synergy was defined as a FICI of ≤0.5. Results: On comparing the two methods used to detect susceptibility to colistin to broth microdilution for MIC (minimum inhibitory concentration) determination, as a reference method, the Vitek showed 100% categorical agreement (CA), on the other hand, the disc diffusion showed CA of 93% with very major errors. Synergy was detected for all isolates (100%) when combining colistin with vancomycin (FICI mean = 0.08). As for azithromycin, 21 strains had FICI range from 0.7 to 1.001, denoting indifference; the remaining 9 strains showed synergy with FICI range from 0.06 to 0.241. The mean colistin/azithromycin FICI was 0.71 for the 30 isolates. Conclusion: These findings suggest that regimens containing vancomycin may confer therapeutic benefit for infection due to XDR-AB; however, other methods (time-kill assay) should be used to confirm such synergy. Furthermore, the optimal combination treatment for serious XDR-AB infection should be addressed in a prospective clinical trial.

Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model.

Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC) for meropenem (MIC ≤ 32 mg/L), combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.

In vitro activities of rifampin, colistin, sulbactam and tigecycline tested alone and in combination against extensively drug-resistant Acinetobacter baumannii

The aim of this study was to investigate the in vitro activities of rifampin, colistin, sulbactam and tigecycline alone and in combination against extensively drug-resistant Acinetobacter baumannii (XDR-Ab). Twenty-five XDR-Ab strains were isolated from patients. Broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) for rifampin, colistin, sulbactam and tigecycline against XDR-Ab strains. The checkerboard microdilution method was used to determine the in vitro activities of potential therapeutic combinations of these four antimicrobial agents. Accordingly, the fractional inhibitory concentration (FIC) and FIC index (FICI) were calculated for each of the combinations. According to our results, when tested as single drugs, rifampin, colistin or tigecycline had good bacteriostatic activity against XDR-Ab, whereas sulbactam was not as active against XDR-Ab isolates. On the other hand, when tested in combination, the combinations of colistin/rifampin, rifampin/sulbactam, rifampin/tigecycline and sulbactam/tigecycline showed good in vitro activities against XDR-Ab isolates. More importantly, these combination regimens could exert addictive or partially synergistic effects at the sub-MIC levels against XDR-Ab strains. Compared with single drugs, most of the combinations of these antimicrobial agents could exert partially synergistic and/or addictive effects, which might provide a better alternative when treating XDR-Ab infections.

Ventilator-associated pneumonia due to extensive drug-resistant Acinetobacter baumannii: Risk factors, clinical features, and outcomes

Acinetobacter baumannii is characterized by a rapid development of resistance to the commonly used antimicrobial agents. We investigated the risk factors, clinical features, and outcomes in ventilator-associated pneumonia (VAP) caused by extensive drug-resistant Acinetobacter baumannii (XDRAB). Clinical parameters and overall in-hospital mortality rates were compared between the VAP with and without XDRAB infection groups. This study showed that VAP caused by XDRAB was not associated with in-hospital mortality. However, it was related to high Simplified Acute Physiology Score II scores and increasing durations of hospital stays.

Risk Factors for Healthcare-Associated Extensively Drug-Resistant Acinetobacter baumannii Infections: A Case-Control Study

The emergence of extensively drug-resistant Acinetobacter baumannii (XDRAB) is a serious threat to hospitalized patients. From 2008 to 2010, surveillance detected 25 hospital-acquired infection (HAI) cases caused by XDRAB at a medical center in Taipei. The site of XDRAB infection was bloodstream (n = 8), urinary tract (n = 12), lower respiratory tract (n = 3), surgical site (n = 1), and cardiovascular (n = 1). The isolates were resistant to all currently available antibiotics except for colistin. The XDRAB isolates are genetically diverse, shown by pulsed-field gel electrophoresis, but 23 of 25 harbored class 1 integron with a 2.3-kb gene cassette. Most of these isolates carry OXA-23 (n = 21) and OXA-51-like carbapenemase genes (n = 25). To identify the risk factors, a case-control study was conducted. The 25 cases were compared with 100 controls randomly selected from hospitalized patients without XDRAB-HAIs, matched by the onset date, ward, and age, at a ratio of 1∶4. Prior use of imipenem, meropenem, piperacillin/tazobactam or fourth-generation cephalosporins (adjusted OR: 3.2, 95% CI: 1.03–10.2, P = 0.04) and >30 days bed-ridden (adjusted OR: 6.0, 95% CI: 1.3–27.6, P = 0.02) were found to be the independent risk factors for XDRAB-HAIs. These findings highlight that, even in the absence of clonal dissemination, XDRAB can emerge under the selective pressure of broad-spectrum antibiotics and causes subsequent HAIs in compromised hosts. An appropriate response to the XDRAB threat therefore should include a component of prudent use of broad-spectrum antibiotics active against gram-negative bacteria.

Epidemiology, Clinical Characteristics and Outcomes of Extensively Drug-Resistant Acinetobacter baumannii Infections among Solid Organ Transplant Recipients

BackgroundExtensively drug-resistant Acinetobacter baumannii (XDR-Ab) has emerged as a major nosocomial pathogen, but optimal treatment regimens are unknown. Although solid organ transplant (SOT) recipients are particularly susceptible to XDR-Ab infections, studies in this population are limited. Our objectives were to determine the epidemiology, clinical characteristics and outcomes of XDR-Ab infections among SOT patients.MethodsA retrospective study of SOT recipients at our center who were colonized or infected with XDR-Ab between November 2006 and December 2011 was conducted. Among infected patients, the primary outcome was survival at 28 days. Secondary outcomes included survival at 90 days and clinical success at 28 days, and XDR-Ab infection recurrence.ResultsXDR-Ab was isolated from 69 SOT patients, of whom 41% (28) and 59% (41) were colonized and infected, respectively. Infections were significantly more common among cardiothoracic than abdominal transplant recipients (p = 0.0004). Ninety-eight percent (40/41) of patients had respiratory tract infections, most commonly ventilator-associated pneumonia (VAP; 88% [36/41]). Survival rates at 28 and 90 days were 54% (22/41) and 46% (19/41), respectively. Treatment with a colistin-carbapenem regimen was an independent predictor of 28-day survival (p = 0.01; odds ratio = 7.88 [95% CI: 1.60–38.76]). Clinical success at 28 days was achieved in 49% (18/37) of patients who received antimicrobial therapy, but 44% (8/18) of successes were associated with infection recurrence within 3 months. Colistin resistance emerged in 18% (2/11) and 100% (3/3) of patients treated with colistin-carbapenem and colistin-tigecycline, respectively (p = 0.03).ConclusionsXDR-Ab causes VAP and other respiratory infections following SOT that are associated with significant recurrence and mortality rates. Cardiothoracic transplant recipients are at greatest risk. Results from this retrospective study suggest that colistin-carbapenem combinations may result in improved clinical responses and survival compared to other regimens and may also limit the emergence of colistin resistance.