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Background. Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone. Methods. This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length. Results. Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46–1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization. Conclusions. In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit. Clinical Trials Registration. NCT01577862.

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

Background: It is controversial whether regular changes of external ventricular drains can reduce cerebrospinal fluid (CSF) infection. Objective: To carry out a randomised controlled clinical trial over a two year period to determine whether a regular change of ventricular catheter every five days could reduce CSF infection and improve outcome. Methods: 103 patients requiring external ventricular drains for more than five days and with no evidence of concurrent CSF infection were studied. The patients were randomised to regular change of ventricular catheter (every five days) and no change unless clinically indicated. Results: The CSF infection rates were 7.8% for the catheter change group and 3.8% for the no change group, respectively (rate ratio = 1.80, 95% confidence interval 0.33 to 9.81, p = 0.50). No significant difference was found in intensive care unit stay, ward stay, or clinical outcome between the two groups. Conclusions: Regular changes of ventricular catheter at five day intervals did not reduce the risk of CSF infection. A single external ventricular drain can be employed for as long as clinically indicated.

Background. With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging. Methods. Patients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry. Results. Twenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates. Conclusions. Colistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

The global spread of carbapenem-resistant Acinetobacter baumannii (A. baumannii) strains has restricted the therapeutic options available to treat infections due to this pathogen. Understanding the prevalence of such infections and the underlying genetic mechanisms of resistance may help in the implementation of adequate measures to control and prevent acquisition of nosocomial infections, especially in an intensive care unit setting. This study describes the molecular characteristics and risk factors associated with OXA-23-producing A. baumannii infections. A case-control study was undertaken from September/2013 to April/2015. Acquisition of OXA-23-producing A. baumannii was found to be associated with the use of nasogastric tubes, haemodialysis, and the use of cephalosporins. These isolates were only susceptible to amikacin, gentamicin, tigecycline, and colistin, and contained the ISAba1 insertion sequence upstream ofblaOXA-23 and blaOXA-51 genes. Twenty-six OXA-23-producing A. baumannii strains belonged to the ST79 (CC79) clonal group,and patients infected or colonised by these isolates had a higher mortality rate (34.6%). In conclusion, this study showed a dissemination of OXA-23-producing A. baumannii strains that was associated with several healthcare-related risk factors and high mortality rates among intensive care unit patients.

Background. Severe Acinetobacter baumannii infections in immunocompetent patients are uncommon, and the virulence mechanisms of this organism are not fully understood. Methods. Following an outbreak of fatal A. baumannii infections in a cohort of relatively immunocompetent patients (low comorbidity and illness severity scores), isolates were investigated with comparative genomics and in animal models. Results. Two unrelated A. baumannii clades were associated with the outbreak. The clone associated with the majority of patient deaths, clade B, is evolutionarily distinct from the 3 international clonal complexes, belongs to multilocus sequence type (MLST) 10, and is most closely related to strains isolated from the Czech Republic, California, and Germany in 1994, 1997, and 2003, respectively. In 2 different murine models, clade B isolates were more virulent than comparator strains, including the highly virulent reference strain AB5075. The most virulent clade B derivative, MRSN 16897, was isolated from the patient with the lowest combined comorbidity/illness severity score. Clade B isolates possess a unique combination of putative virulence genes involved in iron metabolism, protein secretion, and glycosylation, which was leveraged to develop a rapid and specific clinical assay to detect this clade that cannot be distinguished by MLST. Conclusions. Clade B warrants continued surveillance and investigation.

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

BackgroundWe 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/methodsRetrospective 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).ResultsOverall, 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.ConclusionsCFDC 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.Key summary pointsIncreasing real-life data support the clinical effectiveness and safety of cefiderocol (CFDC) for carbapenem resistant Acinetobacter baumannii (CRAB) infections.We investigated CFDC in comparison with colistin (COL) for the treatment of CRAB bloodstream infections (BSI).Clinical cure was higher in CFDC than COL group.Patients with hospital acquired/ventilator-associated pneumonia treated with CFDC had a statistically significant lower 30-d mortality and higher clinical cure than those treated with COL.Adverse events were more frequent in COL than in CFDC-group.CFDC could be an effective and safe treatment option for CRAB BSI, especially in patients with HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.

PurposePredicting infection risk in carbapenem-resistant Acinetobacter baumannii (CRAB) colonized patients may help in improving timely appropriate antibiotic therapy. This study aims to explore risk factors for developing infections in hospitalized patients with previous CRAB colonization.MethodsWe performed an observational retrospective cohort study at ASST Sette Laghi-Varese Hospital between January 2020 and December 2022. All consecutive adult (> 18 years old) hospitalized patients with documented colonization by CRAB at any anatomical site or with CRAB infections preceded by CRAB colonization were included. Univariate and multivariate analyses were performed to investigate infection risk factors.ResultsOverall, 144 patients were included in the study: 104 colonized only and 40 infected patients. Colonization and infection rates significantly changed over the years (2020–2022, p < 0.001). The incidence of infections in CRAB carriers was 27.8% (40/144). Median time from colonization to infection was 4 days (IQR 1-8.5). Overall, inhospital mortality was 32.7% and 55.0% in colonized only and infected patients, respectively. At the multivariable logistic regression cardiovascular disease (OR 5.83, 95% CI 1.12–30.43, p = 0.037), COVID-19 (OR 3.72, 95% CI 1.16–11.91, p = 0.027) and intensive care unit (ICU) admission (OR 8.83, 95% CI 2.94–26.51, p < 0.001) were risk factors independently associated with cardiovascular disease CRAB infection after colonization.ConclusionsWe observed an increased infection risk in patients colonized with CRAB with cardiovascular disease, COVID-19 and admitted in ICU setting. Additional evidence is needed to identify predictors of infection in colonized patients.

Background The global threat of Carbapenem-resistant Acinetobacter baumannii (CRAB) has intensified as resistance to carbapenems continues to rise in recent decades. We aimed to explore risk factors, molecular epidemiology, and antimicrobial therapy of CRAB infection. Methods The clinical data of 110 patients infected with A. baumannii from December 2021 to December 2022 were retrospectively analyzed. Patients were divided into a carbapenem-resistance group (55 patients) and carbapenem-sensitive group (CSAB; 55 patients) based on resistance to carbapenem, and the risk factors of patients infected with CRAB were analyzed. Fifty-five patients with CRAB infection who received antimicrobial therapy were divided into a combination therapy group (45 patients) and a monotherapy group (10 patients), and differences between the two groups were compared. Whole-genome sequencing analysis was performed to assess resistance genes. Phylogenetic analysis was performed to explore the characteristics of CRAB isolates. Results Among the total 110 patients, the rate of poor prognosis in the CRAB group was 43.6% (24/55). Mechanical ventilation (odds ratio [OR] = 5.364, 95% confidence interval [CI] 1.462–19.679, P  = 0.011) and puncture (OR = 19.935, 95% CI 1.261–315.031, P  = 0.012) were independent risk factors for CRAB infection. Of 55 patients in the antimicrobial regimen study, 45 received combination therapy (including dual, triple, or quadruple antibiotic therapy) and 10 received monotherapy. Univariate analysis revealed significant differences between the combination group and monotherapy group for admission to the intensive care unit and wound infection ( P  < 0.05). The CRAB strains of 26 patients taking carbapenem-based combination therapy were mainly ST208, ST1968, and ST195, among which patients with ST1968 strains had higher 28-day mortality. Furthermore, the bla OXA−23 gene was harbored in ST1968, ST195, and ST208. Conclusions Mortality was significantly higher in patients infected with CRAB than with CSAB. Mechanical ventilation and puncture were independent risk factors in predicting CRAB infections. The distribution of CRAB was dominated by ST208, ST1968, and ST195, among which patients with ST1968 had higher 28-day mortality. The bla OXA−23 gene appears to be widely disseminated.