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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.

An understanding of why certain Acinetobacter species are more successful in causing nosocomial infections, transmission and epidemic spread in healthcare institutions compared with other species is lacking. We used genomic, phenotypic and virulence studies to identify differences between Acinetobacter species. Fourteen strains representing nine species were examined. Genomic analysis of six strains showed that the A. baumannii core genome contains many genes important for diverse metabolism and survival in the host. Most of the A. baumannii core genes were also present in one or more of the less clinically successful species. In contrast, when the accessory genome of an individual A. baumannii strain was compared to a strain of a less successful species (A. calcoaceticus RUH2202), many operons with putative virulence function were found to be present only in the A. baumannii strain, including the csu operon, the acinetobactin chromosomal cluster, and bacterial defence mechanisms. Phenotype microarray analysis showed that compared to A. calcoaceticus (RUH2202), A. baumannii ATCC 19606(T) was able to utilise nitrogen sources more effectively and was more tolerant to pH, osmotic and antimicrobial stress. Virulence differences were also observed, with A. baumannii ATCC 19606(T), A. pittii SH024, and A. nosocomialis RUH2624 persisting and forming larger biofilms on human skin than A. calcoaceticus. A. baumannii ATCC 19606(T) and A. pittii SH024 were also able to survive in a murine thigh infection model, whereas the other two species were eradicated. The current study provides important insights into the elucidation of differences in clinical relevance among Acinetobacter species.

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. 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 proliferation of multi-drug resistant (MDR) bacteria is driven by the global spread of epidemic lineages that accumulate antimicrobial resistance genes (ARGs). Acinetobacter baumannii , a leading cause of nosocomial infections, displays resistance to most frontline antimicrobials and represents a significant challenge to public health. In this study, we conduct a comprehensive genomic analysis of over 15,000 A. baumannii genomes to identify a predominant epidemic super-lineage (ESL) accounting for approximately 70% of global isolates. Through hierarchical classification of the ESL into distinct lineages, clusters, and clades, we identified a stepwise evolutionary trajectory responsible for the worldwide expansion and transmission of A. baumannii over the last eight decades. We observed the rise and global spread of a previously unrecognized Clade 2.5.6, which emerged in East Asia in 2006. The epidemic of the clade is linked to the ongoing acquisition of ARGs and virulence factors facilitated by genetic recombination. Our results highlight the necessity for One Health-oriented research and interventions to address the spread of this MDR pathogen. In this study, authors conduct a genomic analysis of 15,000 Acinetobacter baumannii isolates, revealing a dominant multidrug-resistant super-lineage (accounting for approximately 70% global isolates), with Clade 2.5.6 emerging in East Asia in 2006.

Acinetobacter baumannii is a nosocomial pathogen that causes ventilator-associated as well as bloodstream infections in critically ill patients, and the spread of multidrug-resistant Acinetobacter strains is cause for concern. Much of the success of A. baumannii can be directly attributed to its plastic genome, which rapidly mutates when faced with adversity and stress. However, fundamental virulence mechanisms beyond canonical drug resistance were recently uncovered that enable A. baumannii and, to a limited extent, other medically relevant Acinetobacter species to successfully thrive in the health-care environment. In this Review, we explore the molecular features that promote environmental persistence, including desiccation resistance, biofilm formation and motility, and we discuss the most recently identified virulence factors, such as secretion systems, surface glycoconjugates and micronutrient acquisition systems that collectively enable these pathogens to successfully infect their hosts.

Acinetobacter baumannii is an emergent and global nosocomial pathogen. In addition to A. baumannii, other Acinetobacter species, especially those in the Acinetobacter calcoaceticus-baumannii (Acb) complex, have also been associated with serious human infection. Although mechanisms of attachment, persistence on abiotic surfaces, and pathogenesis in A. baumannii have been identified, the genetic mechanisms that explain the emergence of A. baumannii as the most widespread and virulent Acinetobacter species are not fully understood. Recent whole genome sequencing has provided insight into the phylogenetic structure of the genus Acinetobacter. However, a global comparison of genomic features between Acinetobacter spp. has not been described in the literature. In this study, 136 Acinetobacter genomes, including 67 sequenced in this study, were compared to identify the acquisition and loss of genes in the expansion of the Acinetobacter genus. A whole genome phylogeny confirmed that A. baumannii is a monophyletic clade and that the larger Acb complex is also a well-supported monophyletic group. The whole genome phylogeny provided the framework for a global genomic comparison based on a blast score ratio (BSR) analysis. The BSR analysis demonstrated that specific genes have been both lost and acquired in the evolution of A. baumannii. In addition, several genes associated with A. baumannii pathogenesis were found to be more conserved in the Acb complex, and especially in A. baumannii, than in other Acinetobacter genomes; until recently, a global analysis of the distribution and conservation of virulence factors across the genus was not possible. The results demonstrate that the acquisition of specific virulence factors has likely contributed to the widespread persistence and virulence of A. baumannii. The identification of novel features associated with transcriptional regulation and acquired by clades in the Acb complex presents targets for better understanding the evolution of pathogenesis and virulence in the expansion of the genus.

The Acinetobacter calcoaceticus-baumannii complex is a significant cause of nosocomial infections. While A. baumannii is the most common and clinically significant member globally, recent studies suggest that A. pittii is an emerging pathogen within the complex. Clinical A. pittii isolates have not been well characterized. In this study, we investigated the genomic and phenotypic characteristics of six clinical A. pittii isolates from five healthcare facilities. All isolates were resistant to ceftazidime and ertapenem, and one was resistant to imipenem and meropenem. Using whole genome sequencing and phylogenetic analysis, we found that isolates were not linked genetically, harbored OXA-type β-lactamase genes, and exhibited a wide array of virulence factors. Plasmids were identified in two isolates. Transfer of a plasmid carrying bla OXA−72 from AP290R to a carbapenem-susceptible A. bauma nnii recipient strain conferred carbapenem resistance. A. pittii isolates varied in motility and biofilm production. When tested in a Zophobas morio survival model, the carbapenem-resistant strain AP290R showed high virulence and led to increased mortality, reaching 70% within 24 h post-infection. This study highlights the potential of A. pittii to serve as a reservoir of carbapenem resistance and cause severe infections. Infection control efforts to limit the spread of Acinetobacter calcoaceticus-baumannii complex should include A. pittii.

poses a profound global health threat because of multidrug resistance and its association with nosocomial infections. However, standard clinical diagnostics often report it together with other species as complex (ABC), which unavoidably conceals the attribution of non- species. This study reported orthopedic infection cases associated with different species and characterized the genomes of the culture isolates to evaluate their potential impact on the clinical treatment. Nine in-patients with complex identified by culture during hospitalization were enrolled by the Orthopedics Department from a local hospital in Qingdao, China. Their clinical data were reviewed. One ABC isolate from each patient was tested for drug susceptibility and subjected for whole-genome sequencing, followed by bioinformatic analyses. Through whole-genome analysis, nine ABC isolates were identified as six , two , and one with distinct antibiotic resistance profiles and phylogenetic characteristics, indicating progressing pathogen transmission across broad geographic regions in One Health perspective. All and strains carried multidrug resistance genes, while bore only and . Phenotypically, eight isolates were susceptible to almost all the antibiotics tested, with only one being multidrug resistant. Despite this, eight patients received cephalosporins following positive reports of complex. Our study highlighted the limitation of current clinical diagnostic approaches for non- cases, which tended to be overtreated, and suggested that etiology landscape should be explored further beyond to avoid antibiotic misuse.

Introduction Acinetobacter baumannii constitutes a dreadful problem in many ICUs worldwide. The very limited therapeutic options available for these organisms are a matter of great concern. No specific guidelines exist addressing the prevention and management of A. baumannii infections in the critical care setting. Methods Clinical microbiologists, infectious disease specialists and intensive care physicians were invited by the Chair of the Infection Section of the ESICM to participate in a multidisciplinary expert panel. After the selection of clinically relevant questions, this document provides recommendations about the use of microbiological techniques for identification of A. baumannii in clinical laboratories, antibiotic therapy for severe infections and recommendations to control this pathogen in outbreaks and endemic situations. Evidence supporting each statement was graded according to the European Society of Clinical Microbiology and Infection Diseases (ESCMID) grading system. Results Empirical coverage of A. baumannii is recommended in severe infections (severe sepsis or septic shock) occurring during an A. baumannii outbreak, in an endemic setting, or in a previously colonized patient. For these cases, a polymyxin is suggested as part of the empirical treatment in cases of a high suspicion of a carbapenem-resistant (CR) A. baumannii strain. An institutional program including staff education, promotion of hand hygiene, strict contact and isolation precautions, environmental cleaning, targeted active surveillance, and antimicrobial stewardship should be instituted and maintained to combat outbreaks and endemic situations. Conclusions Specific recommendations about prevention and management of A. baumannii infections in the ICU were elaborated by this multidisciplinary panel. The paucity of randomized controlled trials is noteworthy, so these recommendations are mainly based on observational studies and pharmacodynamics modeling.