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The global prevalence of carbapenem‐resistant Acinetobacter baumannii (CRAB) represents a substantial concern for public health. Exogenous adenosine triphosphate (ATP) affects the bactericidal efficacy of meropenem against CRAB; however, the precise mechanism remains elusive. Here, reprogramming metabolomics was employed to delve into the mechanism underlying ATP‐potentiated meropenem lethality against CRAB. Our findings reveal that ATP reprogramming activates the tricarboxylic acid (TCA) cycle in A. baumannii. Notably, the TCA cycle inhibitor malonate antagonised the synergistic bactericidal effect of ATP and meropenem. Activation of the TCA cycle stimulated riboflavin metabolism pathway and the electron transport chain, leading to increased reactive oxygen species (ROS) production. Hydrogen peroxide (H2O2) enhanced meropenem‐mediated killing of CRAB, while the ROS scavenger α‐tocopherol diminished the ATP‐potentiated bactericidal effect. Additionally, ATP upregulated the gene expression of outer membrane porins, including omp33‐36, oprD, ompW, and ompA, thereby improving membrane permeability and elevating intracellular levels of meropenem. The therapeutic synergy of ATP with meropenem was validated in a mouse model of acute pneumonia. This study not only highlights the potential of ATP as a co‐treatment with meropenem but also elucidates the mechanisms by which ATP reverses CRAB resistance, specifically through the promotion of ROS production and enhanced membrane permeability. ATP Potentiates Meropenem Against Carbapenem‐Resistant Acinetobacter baumannii: ROS Promotion and Membrane Permeability Enhancement.

Colistin alone may not be sufficient for treating carbapenem-resistant (CRAB); thus, efforts are needed to increase treatment success rates. We compared the effects of colistin plus carbapenem therapy versus colistin monotherapy in treating pneumonia caused by CRAB and attempted to identify specific populations or factors that could benefit from combination therapy. We retrospectively collected data on cases of CRAB pneumonia. The patients were divided into colistin plus carbapenem therapy and colistin monotherapy groups. The primary outcome was 14-day mortality. The secondary outcomes were in-hospital mortality, clinical improvement at days 2 and 14, and microbiological improvement at day 14. Of 160 cases meeting criteria for CRAB pneumonia, 83 (52%) and 77 (48.0%) were treated with carbapenem combination therapy or colistin monotherapy, respectively. Among these patients, 50 (63.3%) in the combination group and 27 (39.7%) in the monotherapy group had Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores >24 points ( =0.010). Overall, there was no significant difference in 14-day mortality between the combination and monotherapy groups (24.1% vs 20.8%, =0.616). Clinical improvement and sputum-negative conversion also showed no significant difference. After adjusting for disease severity according to APACHE II score, the 14-day mortality was significantly lower in the combination group than in the monotherapy group among patients with APACHE II scores of 25-29 points (9.1% vs 53.8%, =0.020). Despite more severe conditions, compared with colistin monotherapy, colistin plus carbapenem combination therapy showed equivalent primary mortality outcome in treating CRAB pneumonia. Combination therapy was more effective in patients with APACHE II score ranging from 25 to 29 points.

Background Carbapenem‐resistant Acinetobacter baumannii (CRAB) infections are clinically difficult to treat owing to their lack of effective treatments and high mortality rates. This calls for the development of prognostic indicators to facilitate risk stratification and patient management. Aims To identify prognostic indicators of CRAB infections through a systematic review and meta‐analysis. Methods A systematic search was performed on PubMed, Embase, and Cochrane Library up to November 2024. Studies that reported the CRAB infections and their adverse outcomes (e.g., mortality, acute kidney injury, recurrent infections) were eligible for enrollment. Data were extracted from the studies by two reviewers, and the quality of the studies was determined using the Newcastle−Ottawa Scale (NOS). Meta‐analysis was performed using random‐effects or fixed‐effects models while considering the heterogeneity determined using the I² statistics. Results Fourteen studies comprising 2250 patients were enrolled in the study. Notably, cardiovascular disease (OR: 1.59, 95% CI: 1.17–2.17), acute kidney injury (OR: 3.15, 95% CI: 1.69–5.88), shock (OR: 2.33, 95% CI: 1.50–3.63), pneumonia (OR: 1.28, 95% CI: 1.02–1.60), hematologic malignancy (OR: 2.23, 95% CI: 1.55–3.21), neutropenia (OR: 2.74, 95% CI: 1.48–5.06), and thrombocytopenia (OR: 1.49, 95% CI: 1.10–2.02) were found to be significant prognostic indicators predicting poor outcomes. The use of steroid therapy (OR: 1.29, 95% CI: 1.01–1.64) was linked to increased mortality risk. Conclusion In this meta‐analysis, we detected several prognostic indicators that correlated with poor adverse outcomes in patients with CRAB infections, which may help clinical decision‐making and risk‐stratification strategies. Trial Registration: PROSPERO 2024 CRD42024565429 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024565429.

To evaluate the clinical characteristics, antimicrobial resistance (AMR) phenotypes and genotypes, and homology features of carbapenem-resistant (CRAB) in intensive care unit (ICU) and to provide basis for effectively prevention, control and treatment of nosocomial infections caused by CRAB. A total of 39 CRAB strains isolated from hospitalized patients in the ICU and neurosurgical ICU (NICU) between 2020 and 2023 were subjected to antimicrobial susceptibility testing and whole-genome sequencing (WGS). Virulence factor genes (VFGs), antimicrobial resistance genes (ARGs), multilocus sequencing typing (MLST), complete genome multilocus sequencing typing (cgMLST), average nucleotide identity (ANI), and single nucleotide polymorphism (SNP) analyses were performed using WGS. All CRAB strains were 100% resistant to ciprofloxacin, ceftazidime, piperacillin/tazobactam, and ticarcillin/clavulanic acid. A total of 48 antimicrobial resistance genes (ARGs) were found in the 39 CRAB strains, including OXA-66, OXA-23, ADC-30, ADC-73, which confered resistance to carbapenems, cephalosporins, fluoroquinolones, aminoglycosides, tetracycline and sulfonamides. There were 128 VFGs, including genes encoding the AdeFGH efflux pump, lipopolysaccharide (LpsBLC), outer membrane protein A (OmpA), penicillin-binding protein (PbpG), biofilm-associated proteins (bap, pgaBCD, CsuABCDE), type VI secretion system protein (Tss), quorum sensing protein (AbaI/AbaR). Six clonal lineages were identified by Oxford MLST method, whereas one sequence type (ST2) was identified using the Pasteur MLST method. ANI analysis, heat map of SNP analysis, and phylogenetic tree based on core SNP revealed six clusters, and the strain classification results were consistent with these different methods. Ten clonal lineages were identified by cgMLST. The CRAB strains were ST2 clones accompanied by severe resistance to commonly used antibiotics and abundant ARGs and VFGs in genotype. Strict measures should be implemented to prevent and control transmissions and infections. CgMLST and SNPs analyses showed excellent discriminatory power in homology analysis.

Carbapenem-resistant gram-negative bacteria including Enterobacteriaceae as well as nonfermenters, such as Pseudomonas aeruginosa and Acinetobacter baumannii, have emerged as significant global clinical threats. Although new agents have recently been approved, none are active across the entire range of resistance mechanisms presented by carbapenem-resistant gram-negative bacteria. Cefiderocol, a novel siderophore cephalosporin, has been shown in large surveillance programs and independent in vitro studies to be highly active against all key gram-negative causative pathogens isolated from patients with hospital-acquired or ventilator-associated pneumonia, bloodstream infections, or complicated urinary tract infections. The improved structure, the novel mode of entry into bacteria, and its stability against carbapenemases enables cefiderocol to exhibit high potency against isolates that produce carbapenemases of all classes or are resistant due to porin channel mutations and/or efflux pump overexpression. Resistance to cefiderocol is uncommon and appears to be multifactorial.

Biofilm-mediated infections are critical to public health and a leading cause of resistance among pathogens, amounting to a prolonged hospital stay and increased mortality rate in the intensive care unit. In this study, the antibacterial and antibiofilm activities of rifampicin or carbapenem monotherapies were compared with rifampicin and carbapenem combination therapies against rifampicin-resistant and carbapenem-resistant Acinetobacter baumannii isolates. Among 29 CRAB isolates, 24/29 (83%) were resistant to rifampicin, with MIC values between 2–256 µg/mL. Checkerboard assays disclosed that combination therapies at FICIs between 1/8 and 1/4 improved the activity of carbapenems at subinhibitory concentrations. Time-kill kinetics indicated a 2- to 4-log reduction at 1/2 MIC rifampicin + 1/4 MIC carbapenem and 1/4 MIC rifampicin + 1/4 MIC carbapenem against the isolates, with the MIC values ranging from 2–8 µg/mL. The MTT assay revealed a dose-dependent decrease of the cell viability of established bacterial biofilm at 4 MIC rifampicin + 2 MIC carbapenems, with a percentage reduction of 44–75%, compared with monotherapies at 16 MIC. Scanning electron microscopy further confirmed bacterial cell membrane disruption, suggesting a synergism between carbapenem and rifampicin against a representative isolate. The findings demonstrated that the combination of rifampicin with carbapenems could improve antibacterial activities and eradicate established Acinetobacter baumannii biofilm.

Phage therapy is recognized as a promising alternative to antibiotics in treating pulmonary bacterial infections, however, its use has not been reported for treating secondary bacterial infections during virus pandemics such as coronavirus disease 2019 (COVID-19). We enrolled 4 patients hospitalized with critical COVID-19 and pulmonary carbapenem-resistant Acinetobacter baumannii (CRAB) infections to compassionate phage therapy (at 2 successive doses of 10 9 plaque-forming unit phages). All patients in our COVID-19-specific intensive care unit (ICU) with CRAB positive in bronchoalveolar lavage fluid or sputum samples were eligible for study inclusion if antibiotic treatment failed to eradicate their CRAB infections. While phage susceptibility testing revealed an identical profile of CRAB strains from these patients, treatment with a pre-optimized 2-phage cocktail was associated with reduced CRAB burdens. Our results suggest the potential of phages on rapid responses to secondary CRAB outbreak in COVID-19 patients.

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.

Overuse of antibiotics in clinical medicine has contributed to the global spread of multidrug-resistant bacterial pathogens, including Acinetobacter baumannii . We present a case of an 88-year-old Chinese man who developed hospital-acquired pneumonia caused by carbapenem-resistant A. baumannii (CRAB). A personalized lytic pathogen-specific single-phage preparation was nebulized to the patient continuously for 16 days in combination with tigecycline and polymyxin E. The treatment was well tolerated and resulted in clearance of the pathogen and clinical improvement of the patient’s lung function.

Carbapenem-Resistant Acinetobacter baumannii (CRAB) outbreak in intensive care units (ICUs) is a significant problem for healthcare facilities. In this study, we aimed to investigate the occurrence of CRAB isolates among ICU-admitted patients during the three waves of the COVID-19 pandemic in Iran using Multiple-Locus Variable Number Tandem-Repeat Analysis (MLVA). We obtained 50 (A) baumannii isolates from tracheal aspirate and blood culture samples. In the disc diffusion method, all isolates were cefotaxime, ceftriaxone, and cefepime-resistant, while 98% (49/50) of isolates were resistant to piperacillin, piperacillin-tazobactam, ceftazidime, and ciprofloxacin. Levofloxacin and tobramycin resistance was found in 76% (38/50) of isolates. In the microbroth dilution test all isolates were resistant to imipenem, 98% (49/50) to meropenem, 68% (34/50) to colistin, and 20% (10/50) to polymyxin (B) Based on the PCR findings, all isolates harbored bla OXA−40 , ISAba-1 , and int-2 genes. There were no isolates found that have the bla OXA−58 , bla OXA−143 , bla VEB−1 , bla VIM , and int-3 genes. Among Extended-spectrum beta-lactamases (ESBL) genes, bla CTX−M , bla TEM , bla SHV , bla GES , and bla PER−1 have a prevalence of 42% (21/50), 84% (42/50), 58% (29/50), 78% (39/50), and 54% (27/50), respectively. 74% (37/50) of the isolates had the bla OXA−23 gene, while all of the isolates carried the bla OXA−40 gene. Among MBL genes, bla IPM , bla GIM , bla SIM , and bla NDM−1 have a prevalence of 20% (10/50), 8% (4/50), 22% (11/50), and 60% (30/50), respectively. The prevalence of int-1 was documented as 74% (37/50). Accordingly, all isolates were identified as CRAB. The co-existence of bla OXA−23 /int-2 and bla OXA−23 /isaba-1 was 74% (37/50). The co-existence of bla NDM−1 / ISAba-1 was observed in 30 (60%) isolates. Using an 80% similarity threshold on the dendrogram constructed through MLVA typing, all isolates were grouped into two clusters: cluster A with 9 isolates from wave 3, and cluster B with 41 isolates from waves 3, 4, and 5. Our study confirms a clonal transmission of CRAB during the study period and suggests using molecular typing methods like MLVA in healthcare settings to identify dominant clones, antibiotic resistance patterns, and transmission routes. This will help to better manage the emergence and spread of antibiotic-resistant strains in future outbreaks.