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BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Purpose: Predicting 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. Methods: We 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. Results: Overall, 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. Conclusions: We 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. [ABSTRACT FROM AUTHOR]

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 blaOXA−40, ISAba-1, and int-2 genes. There were no isolates found that have the blaOXA−58, blaOXA−143, blaVEB−1, blaVIM, and int-3 genes. Among Extended-spectrum beta-lactamases (ESBL) genes, blaCTX−M, blaTEM, blaSHV, blaGES, and blaPER−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 blaOXA−23 gene, while all of the isolates carried the blaOXA−40 gene. Among MBL genes, blaIPM, blaGIM, blaSIM, and blaNDM−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 blaOXA−23/int-2 and blaOXA−23/isaba-1 was 74% (37/50). The co-existence of blaNDM−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. [ABSTRACT FROM AUTHOR]

Phage therapy is gaining increasing interest in the fight against critically antibiotic-resistant nosocomial pathogens. However, the narrow host range of bacteriophages hampers the development of broadly effective phage therapeutics and demands precision approaches. Here, we combine large-scale phylogeographic analysis with high-throughput phage typing to guide the development of precision phage cocktails targeting carbapenem-resistant Acinetobacter baumannii , a top-priority pathogen. Our analysis reveals that a few strain types dominate infections in each world region, with their geographical distribution remaining stable within 6 years. As we demonstrate in Eastern Europe, this spatiotemporal distribution enables preemptive preparation of region-specific phage collections that target most local infections. Finally, we showcase the efficacy of phage cocktails against prevalent strain types using in vitro and animal infection models. Ultimately, genomic surveillance identifies patients benefiting from the same phages across geographical scales, thus providing a scalable framework for precision phage therapy. [Display omitted] • A few CRAB types dominate infections in individual world regions • Phylogeography reveals stable strain composition for countries over 6 years • Spatiotemporal distribution informs the development of region-specific phage collections • Phage cocktails are effective against the most prevalent strain types in Eastern Europe By mapping the genetic diversity and geographic distribution of carbapenem-resistant Acinetobacter baumannii , bacteriophage cocktails were developed and designed to treat the maximum number of patients within a specific geographic region. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Acinetobacter baumannii (Ab) disease in the United States is commonly attributed to outbreaks of 1 or 2 monophyletic carbapenem resistance (CR) Ab lineages that vary by region. However, there is limited knowledge regarding CR Ab epidemiology and population structures in the U.S. Deep South, and few studies compare contemporary CR and carbapenem-susceptible (Cs) Ab , despite relative prevalence of the latter. Methods We performed a multiyear analysis of 2462 Ab cases in a large healthcare system in Birmingham, AL, and 89 post-2021 Ab isolates were sequenced and phenotyped by antibiotic susceptibility tests. Results Although the cumulative CR rate was 17.7% in our cohort, rates regularly increased in winter months as result of seasonal changes in case incidence of Cs Ab , specifically. Genotyped CR Ab belonged to clonal group (CG) 1, CG2, CG108, CG250, or CG499, with local clones of CG108, CG250, and CG499 persisting over multiple months. There was no clonal expansion of any Cs Ab lineage. Among CR Ab isolates, levels of β-lactam antibiotic resistance and the repertoire of related genetic resistance determinants, which included the novel CR-conferring FtsI A515V polymorphism, differed according to CG. CG108 and CG499 isolates displayed specific heteroresistance to sulbactam and trimethoprim/sulfamethoxazole, respectively, which resulted in discrepant susceptibility results in microbroth versus agar-based antibiotic susceptibility tests modalities. Conclusions We report an unusually high degree of CR Ab phylogenetic diversity principally driven by emergent U.S. lineages harboring novel resistance elements that must be incorporated into diagnostic, surveillance, and preclinical research efforts. [ABSTRACT FROM AUTHOR]

A carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak in an intensive care unit (ICU) was contained by an improved infection-control measure that included a disinfectant policy. In our retrospective cohort study, we describe the epidemiological investigations and infection-control measures during this outbreak. Descriptive analysis was used to summarize patient demographics, neurological diseases, surgical treatment, underlying diseases, infection, and outcomes. In December 2023, two CARB-positive patients were observed in the ICU, and four more patients became CRAB-positive in January. During this outbreak, there was an overlap of hospitalization periods among the CRAB-positive patients, and CRAB was isolated from the environment; the isolated CRAB strain was identical. Infection-control measures, including hand hygiene, contact precautions and isolation, surveillance, decolonization, environmental cleaning, and disinfection, were reviewed and modified. The aim of this study was to examine the molecular background of the effectiveness of the disinfectant shift used during successful outbreak control. Experiments were carried out to study the phenotypic sensitivity and genetic background of different disinfectant agents. A thorough analysis of the detected CRAB strain included whole-genome sequencing (WGS), investigation of the qacE and qacEΔ1 genes' relative expression by qPCR after exposure to different disinfectant solutions, as well as an analysis of biofilm formation. WGS analysis of the CRAB strain identified that an ST2 high-risk clone was responsible for the outbreak, which produced OXA-83 and ADC-30 beta-lactamases; in addition, qacE and qacEΔ1 genes were also detected, which confer resistance to disinfectants containing quaternary ammonium compounds (QACs). A qPCR analysis demonstrated that after exposure to different disinfectants, the gene expression levels of qacE and qacEΔ1 increased and correlated with concentrations of QACs of disinfectants. During the outbreak, the standard-of-care QAC-based disinfectant was changed to a mainly alcohol-based agent in the ICU, which contributed to the successful control of this outbreak, and no additional patients were identified with CRAB. We conclude that continuous surveillance and hand hygiene training combined with fast identification and reaction to new cases, as well as an in-depth analysis of multidrug-resistant outbreak strains and investigation of their disinfectant tolerance/resistance during an outbreak, are essential to effectively control the spread of nosocomial pathogens. The smart policy of disinfectant agent selection played a crucial role in controlling the outbreak and ensuring patient safety in the ICU. [ABSTRACT FROM AUTHOR]

Abstract 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.

Xiaotong Tian,1,2 Jing Lin,1,2 Menglan Zhou,3,4 Ying Ge,1 Taisheng Li,1 Li Zhang,1 Zhengyin Liu1 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of ChinaCorrespondence: Zhengyin Liu; Li Zhang, Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China, Email liuzhy@pumch.cn; zhangli36@pumch.cnPurpose: To evaluate the clinical outcomes and safety of tigecycline (TGC) plus cefoperazone/sulbactam (CPS) or TGC monotherapy in patients with hospital-acquired pneumonia (HAP) caused by Carbapenem-Resistant Acinetobacter baumannii (CRAB).Methods: This was a retrospective analysis of multicenter data from 62 Chinese hospitals with CRAB HAP. Risk factors for receiving TGC with CPS therapy and predictors of mortality were assessed using multivariate logistic and Cox regression analyses, respectively. Propensity score matching (PSM) evaluated the efficacy and safety of antimicrobial regimens.Results: A total of the 180 patients were included, with 95 receiving TGC monotherapy and 85 receiving combination therapy. Multivariate logistic regression analysis revealed that older age (P = 0.011), and intensive care unit (ICU) admission (P = 0.007) were significant risk factors for combination therapy. Multivariate Cox regression demonstrated that combination therapy was associated with a significantly higher risk of 90-day mortality (P = 0.031). Patients in the standard-dose TGC (SDT) plus CPS subgroup had significantly higher rates of SOFA scores ≥ 7 (P = 0.009) and MV used (P = 0.028), as well as higher 30-/90-day mortality compared to high-dose TGC (HDT) plus CPS group. TGC plus CPS significantly reduced CRP levels (P = 0.009), while the variations in ALT, TBIL, Cr, Hb, and PLT levels did not differ between different antimicrobial regimens after PSM.Conclusion: HDT and CPS combination therapy was more effective in patients with advanced age and more severe condition. Safety profiles of different antimicrobial regimens were similar with liver, kidneys, and coagulation functions.Keywords: carbapenem-resistant Acinetobacter baumannii, hospital acquired pneumonia, tigecycline, cefoperazone/sulbactam, risk factors

Abstract 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.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a Priority 1 (Critical) pathogen urgently requiring new antibiotics. Polymyxins are a last-line option against CRAB-associated infections. This transcriptomic study utilized a CRAB strain to investigate mechanisms of bacterial killing with polymyxin B, colistin, colistin B, and colistin/sulbactam combination therapy. After 4 h of 2 mg/L polymyxin monotherapy, all polymyxins exhibited common transcriptomic responses which primarily involved disruption to amino acid and fatty acid metabolism. Of the three monotherapies, polymyxin B induced the greatest number of differentially expressed genes (DEGs), including for genes involved with fatty acid metabolism. Gene disturbances with colistin and colistin B were highly similar (89 % common genes for colistin B), though effects on gene expression were generally lower (0–1.5-fold in most cases) with colistin B. Colistin alone (2 mg/L) or combined with sulbactam (64 mg/L) resulted in rapid membrane disruption as early as 1 h. Transcriptomic analysis of this combination revealed that the effects were driven by colistin, which included disturbances in fatty acid synthesis and catabolism, and inhibition of nutrient uptake. Combination therapy produced substantially higher fold changes in 72 % of DEGs shared with monotherapy, leading to substantially greater reductions in fatty acid biosynthesis and increases in biofilm, cell wall, and phospholipid synthesis. This indicates synergistic bacterial killing with the colistin/sulbactam combination results from a systematic increase in perturbation of many genes associated with bacterial metabolism. These mechanistic insights enhance our understanding of bacterial responses to polymyxin mono- and combination therapy and will assist to optimize polymyxin use in patients.

Ning Du,1,&ast; Dan You,2,&ast; Dava Tenzing,3 Dongxiang Qu,2 Jun Meng,1,&ast; Yihui Wang,4,&ast; Juan He5,&ast; 1Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Pharmacy, The First Hospital of Qiqihar, Qiqihar, Heilongjiang Province, People’s Republic of China; 3Department of Emergency, People’s Hospital of Shigatse City, Shigatse, Xizang Autonomous Region, People’s Republic of China; 4Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan He, Department of Pharmacy, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email hejuanwin@126.com Yihui Wang, Department of Emergency, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email wangyihui581@163.comPurpose: Infection with carbapenem-resistant Acinetobacter baumannii (CRAB) is a tough nut to crack. Carrimycin is a novel recombinant macrolide antibiotic, and has good anti-infection effects in vivo. At present, it is rarely reported for treatment of CRAB infection. We present a case where a patient with COVID-19 complicated by CRAB infection was successfully treated with a combination therapy including carrimycin, offering clinical insights and experience.Patients and Methods: The patient infected with CRAB was cured by carrimycin combined with tigecycline and amikacin ultimately. We analyzed and summarized the therapeutic regimen and disease feature to provide reference for clinical treatment.Results: The patient was admitted to emergency observation wards with fever and was diagnosed with COVID-19 pneumonia. During the treatment, his condition worsened. He had a fever, cough, and expectoration. After 3 days of empirical treatment with meropenem, tested positive for A. baumannii infection by the next-generation sequencing, and CRAB was detected in blood and sputum culture. Then, he was administered with tigecycline and amikacin immediately for 5 days, however the therapeutic effect was not significant. The patient still remained in a high inflammatory response. Ultimately, the treatment regimen was changed to carrimycin combined with tigecycline and amikacin for 7 days, and then carrimycin combined with tigecycline for 10 days, the patient’s clinical condition gradually improved. The patient received carrimycin monotherapy for 7 days, then discharged.Conclusion: Carrimycin may be a bright alternative for CRAB infection as one of the drugs in combination therapy, especially in a patient with hyperinflammatory response.Keywords: Carrimycin, Carbapenem-resistant Acinetobacter baumannii, CRAB, case report

We investigated the activity of cefiderocol/β-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most "Critical Priority" group of MDR bacteria (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log10 CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii; of the cefiderocol/avibactam combination against carbapenem-resistant Enterobacterales; and of the cefiderocol/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all β-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol/avibactam was only active against carbapenem-resistant Enterobacterales. [ABSTRACT FROM AUTHOR]

Summary: We present our findings on interpatient transmission, epidemic control measures, and the outcomes of a series of ten critically ill burn patients who were either colonized or infected with carbapenem-resistant Acinetobacter baumannii (CRAB). None of the five infected patients achieved clinical cure, and all experienced relapses. Microbiological failure was observed in 40% of the infected patients. The isolated CRAB strains were found to carry blaOXA−23 and armA resistance genes. Despite the lack of clinical cure, all five infected patients survived and were discharged from the Burn Intensive Care Unit. [ABSTRACT FROM AUTHOR]

The environmental surveillance of air grilles in clinical areas has not been systematically analysed. Samples were collected from frequently touched items (N = 529), air supply (N = 295) and exhaust (N = 184) grilles in six medical and 11 surgical wards for the cultures of multi-drug-resistant organisms (MDROs): meticillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenemase-producing Enterobacterales (CPE), and isolates were selected for whole-genome sequencing (WGS). The contamination rates were correlated with the colonization pressures of the respective MDROs. From 3rd October to 21st November 2023, 9.8% (99/1008) of the samples tested positive, with MRSA (24.2%, 24/99), CRAB (59.6%, 59/99) and CPE (2.0%, 2/99), being the only detected MDROs. The contamination rate in air exhaust grilles (26.6%, 49/184) was significantly higher than in air supply grilles (5.8%, 17/295; P <0.001). The contamination rate of air exhaust grilles with any MDRO in acute medical wards (73.7%, 14/19) was significantly higher than in surgical wards (12.5%, 4/32; P <0.001). However, there was no difference in the contamination rate of air exhaust grilles between those located inside and outside the cohort cubicles for MDROs (27.1%, 13/48 vs 28.8%, 30/104; P =0.823). Nevertheless, the weekly CRAB colonization pressure showed a significant correlation with the overall environmental contamination rate (r = 0.878; 95% confidence interval (CI): 0.136–0.986; P =0.004), as well as with the contamination rate in air supply grilles (r = 0.960; 95% CI: 0.375–0.999; P <0.001) and air exhaust grilles (r = 0.850; 95% CI: 0.401–0.980; P =0.008). WGS demonstrated clonal relatedness of isolates collected from patients and air exhaust grilles. Air grilles may serve as MDRO reservoirs. Cohort nursing in open cubicles may not completely prevent MDRO transmission through air dispersal, prompting the consideration of future hospital design. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a challenging multidrug-resistant pathogen in healthcare. Phage vB_AbaSi_W9 (GenBank: PP146379.1), identified in our previous study, shows lytic activity against 26 (89.66%) of 29 carbapenem-resistant Acinetobacter baumannii (CRAB) strains with various sequence types (STs). It is a promising candidate for CRAB treatment; however, its lytic efficiency is insufficient for complete bacterial lysis. Therefore, this study aimed to investigate the clinical utility of the phage vB_AbaSi_W9 by identifying antimicrobial agents that show synergistic effects when combined with it. The A. baumannii ATCC17978 strain was used as the host for the phage vB_AbaSi_W9. Adsorption and one-step growth assays of the phage vB_AbaSi_W9 were performed at MOIs of 0.001 and 0.01, respectively. Four clinical strains of CRAB belonging to different sequence types, KBN10P04948 (ST191), LIS2013230 (ST208), KBN10P05982 (ST369), and KBN10P05231 (ST451), were used to investigate phage–antibiotic synergy. Five antibiotics were tested at the following concentration: meropenem (0.25–512 µg/mL); colistin, tigecycline, and rifampicin (0.25–256 µg/mL); and ampicillin/sulbactam (0.25/0.125–512/256 µg/mL). The in vitro synergistic effect of the phage and rifampicin was verified through an in vivo mouse infection model. Phage vB_AbaSi_W9 demonstrated 90% adsorption to host cells in 1 min, a 20 min latent period, and a burst size of 114 PFU/cell. Experiments combining phage vB_AbaSi_W9 with antibiotics demonstrated a pronounced synergistic effect against clinical strains when used with tigecycline and rifampicin. In a mouse model infected with CRAB KBN10P04948 (ST191), the group treated with rifampicin (100 μg/mL) and phage vB_AbaSi_W9 (MOI 1) achieved a 100% survival rate—a significant improvement over the phage-only treatment (8.3% survival rate) or antibiotic-only treatment (25% survival rate) groups. The bacteriophage vB_AbaSi_W9 demonstrated excellent synergy against CRAB strains when combined with tigecycline and rifampicin, suggesting potential candidates for phage–antibiotic combination therapy in treating CRAB infections. [ABSTRACT FROM AUTHOR]

Background: We 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/methods: Retrospective 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). Results: Overall, 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. Conclusions: CFDC 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 points: Increasing 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. [ABSTRACT FROM AUTHOR]

Background We examined temporal trends in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in a hospital with hyperendemic CRAB and assessed the efficacy of varied infection control strategies in different ward types. Methods We retrospectively analyzed all CRAB clinical samples from 2006 to 2019 and categorized infections as hospital-onset (HO) or community-onset. We used interrupted time series analysis to assess the impact of interventions on the incidence of all HO-CRAB infections and bloodstream infections (BSIs) at the hospital and ward group levels. Results Over 14 years, 4009 CRAB infections were identified (89.7% HO), with 813 CRAB BSI (93.2% HO). The incidence per 100 000 patient-days of CRAB infections peaked in 2008 at 79.1, and that of CRAB BSI peaked in 2010 at 16.2. These rates decreased by two-thirds by 2019. In the general intensive care unit (ICU), hand hygiene and environmental cleaning interventions were followed by a significant reduction in the level of HO-CRAB infections, with an additional decrease in the slope after the introduction of active surveillance and 2% chlorhexidine bathing. In the surgical ICU and surgical department, a reduction in slope or level of CRAB infection was observed after moving ventilated patients to single rooms. In medical wards, a multimodal intervention was followed by a reduction in the slope of HO-CRAB infections and BSIs. In wards where CRAB infections were uncommon, the incidence of HO-CRAB infections decreased throughout the study period. Conclusions Ward-specific variables determine the success of interventions in reducing CRAB infections; therefore, interventions should be tailored to each setting. [ABSTRACT FROM AUTHOR]

IntroductionThe extent to which sinks are contaminated by carbapenem-resistant Acinetobacter baumannii (CRAB) in intensive care units (ICUs) and the association between these contaminated sinks and hospital-acquired CRAB infections during the non-cluster period remains largely unknown. Here, we performed a prospective multicenter study in 16 ICUs at 11 tertiary hospitals in Chengdu, China.MethodsWe sampled sinks, collected CRAB clinical isolates, and conducted whole-genome sequencing and analysis.ResultsA total of 789 swabs were collected from 158 sinks, and 16 CRAB isolates were recovered from 16 sinks, resulting in a contamination rate of 10.16%. Twenty-seven clinical isolates were collected during the study period. The majority (97.67%, 42/43) of the CRAB isolates belonged to ST2, and 36 (83.72%) of them had both blaOXA-23 and blaOXA-66. The 43 strains belonged to 12 clones. One certain clone caused multiple contaminations of seven sinks in one GICU. Two clones of ST2 blaOXA-23 and blaOXA-66-carrying sink strains were likely the sources of the two clusters in the two GICUs, respectively. Five ST2 blaOXA-23-carrying isolates were found to be common clones but were recovered from two hospitals.ConclusionThe contamination rate of CRAB in handwashing sinks is high in some local ICUs, and the contaminated sinks can serve as environmental reservoirs for CRAB clusters.

ABSTRACT Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant threat to hospitalized patients as effective therapeutic options are scarce. Based on the genomic characteristics of the CRAB strain AB2877 harboring chromosome-borne blaOXA-23, which was isolated from the bronchoalveolar lavage fluid (BALF) of a patient in a respiratory intensive care unit (RICU), we systematically analyzed antibiotic resistance genes (ARGs) and the genetic context associated with ARGs carried by CRAB strains harboring chromosome-borne blaOXA-23 worldwide. Besides blaOXA-23, other ARGs were detected on the chromosome of the CRAB strain AB2877 belonging to ST208/1806 (Oxford MLST scheme). Several key genetic contexts associated with the ARGs were identified on the chromosome of the CRAB strain AB2877, including (1) the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph(6)-Id (2); the resistance island AbGRI3 harboring armA and mph(E)-msr(E) (3); the Tn3-like composite transposon containing blaTEM-1D and aph(3')-Ia; and (4) the structure “ISAba1-blaADC-25.” The first two genetic contexts were most common in ST195/1816, followed by ST208/1806. The last two genetic contexts were found most frequently in ST208/1806, followed by ST195/1816.IMPORTANCEThe blaOXA-23 gene can be carried by plasmid or chromosome, facilitating horizontal genetic transfer and increasing carbapenem resistance in healthcare settings. In this study, we focused on the genomic characteristics of CRAB strains harboring the chromosome-borne blaOXA-23 gene, and the important genetic contexts associated with blaOXA-23 and other ARGs were identified, and their prevalent clones worldwide were determined. Notably, although the predominant clonal CRAB lineages worldwide containing the MDR region associated with blaOXA-23, tet(B)-tetR(B), aph(3'')-Ib, and aph (6)-Id was ST195/1816, followed by ST208/1806, the CRAB strain AB2877 in our study belonged to ST208/1806. Our findings contribute to the knowledge regarding the dissemination of CRAB strains and the control of nosocomial infection.

Objectives: This study analyzed the risk and impact of developing pneumogenic bacteremia in patients with CRAB nosocomial pneumonia in ICU. Methods: This is multicenter retrospective study. Clinical outcomes were compared between bacteremia and non-bacteremia group, and the risk factors for mortality and developing pneumogenic CRAB bacteremia were analyzed. Results: After patient recruitment, 164 cases were in the bacteremia group, and 519 cases were in the non-bacteremia group. The bacteremia group had 22.4 percentage of increase in-hospital mortality than the non-bacteremia group (68.3% vs 45.9%, P < 0.001). Multivariate analysis showed bacteremia was an independent risk factor for in-hospital mortality (aHR = 2.399, P < 0.001). A long time-interval between ICU admission and pneumonia onset was an independent risk factor for developing bacteremia (aOR = 1.040, P = < 0.001). Spearman's rank correlation analysis indicated a high correlation between the days from ICU admission to pneumonia onset and the days of ventilator use before pneumonia onset (correlation coefficient (ρ) = 0.777). Conclusions: In patients with CRAB nosocomial pneumonia, bacteremia increased the in-hospital mortality, and a longer interval from ICU admission to pneumonia onset was an independent risk factor for developing bacteremia, which was highly associated with the use of mechanical ventilation.

ObjectiveTo investigate a suspected outbreak of carbapenem-resistant Acinetobacter baumannii （CRAB） nosocomial infection in an intensive care unit （ICU） and provide scientific evidence for prevention and control of multi-drug resistant nosocomial infection.MethodsClinical and epidemiological data of 4 patients with CRAB infection were retrospectively investigated in the ICU of Renji Hospital in November 2021. Environmental hygiene monitoring and multilocus sequence typing （MLST） were conducted and intervention measures were taken.ResultsA total of 4 cases with CRAB infection were identified， among which 1 case was determined to be community-acquired and 3 cases were hospital-acquired. The isolated strains shared the same drug resistance， and were all classified into ST368 type. In the surface and hand samples （n=40）， 2 CRAB strains were detected in the air filter beside the bed of the first case， with a detection rate of 5%. After adopting comprehensive prevention and control strategies， including environmental cleaning and disinfection， hand hygiene， staff management and training， and supervision， no similar case with CRAB infection was found.ConclusionThis suspected outbreak of CRAB nosocomial infection may be induced by inadequate environmental cleaning and disinfection， and inadequate implementation of hand hygiene. Timely identification， investigation， and targeted measures remain crucial to effective control of possible nosocomial infection.

The emergence and spread of Acinetobacter baumannii pose a severe threat to public health, highlighting the urgent need for the next generation of therapeutics due to its increasing resistance to existing antibiotics. BfmR, a response regulator modulating virulence and antimicrobial resistance, shows a promising potential as a novel antimicrobial target. Developing BfmR inhibitors may propel a new therapeutic direction for intractable infection of resistant strains. In this study, we conducted a structure-based hierarchical virtual screening pipeline combining molecular docking, molecular dynamic simulation, and MM/GBSA calculation to sift the Specs chemical library and finally discover three novel potential BfmR inhibitors. The three hits can reduce the MIC of meropenem for the carbapenem-resistant Acinetobacter baumannii (CRAB) strain ZJ06. Similar to the BfmR knockout strain, Cmp-98 was demonstrated to downregulate the expression of K locus genes, indicating it as a BfmR inhibitor. Bacteria underwent harmful morphological changes after treatment with these inhibitors. Molecular dynamic simulations found that all the hits tend to dynamically bind to different positions of the phosphorylation site of BfmR. Wherein we identified a potential inhibitory-binding cleft, beside a possible activated binding cleft at the edge of the phosphorylation site. Restraining the ligand binding poses may help exert inhibitory effects. This study reports a group of new scaffold BfmR inhibitors, offering new insights for novel antibiotic therapeutics against CRAB.

Objective To evaluate the effectiveness of multi-disciplinary team (MDT) mode in the prevention and control of multidrug resistant organism (MDRO) infection in lung transplant recipients. Methods Lung transplant recipients admitted to the hospital from 2019 to 2022 were enrolled. MDT expert group was established in January, 2020. A series of prevention and control measures were conducted. The implementation rate of MDRO prevention and control measures and the detection rate of MDRO on the environmental surface from 2020 to 2022, and the detection rate of MDRO in lung transplant recipients from 2019 to 2022 were analyzed. Results The overall implementation rate of MDRO prevention and control measures for medical staff was increased from 64.9% in 2020 to 91.6% in 2022, showing an increasing trend year by year (P<0.05). The detection rate of MDRO on the environmental surface was decreased from 28% in 2020 to 9% in 2022, showing a downward trend year by year (P<0.05). The detection rate of MDRO in lung transplant recipients was decreased from 66.7% in 2019 to 44.3% in 2022, showing a decreasing trend year by year (P<0.001). Conclusions MDT mode management may enhance the implementation of MDRO prevention and control measures for medical staff, effectively reduce the infection rate of MDRO in lung transplant recipients and the detection rate of MDRO on the environmental surface, which is worthy of widespread application. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty- five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) and its emerging evolutionary branch toward hypervirulence have been neglected in pregnancy. Methods: From September 2020 to August 2021, an active surveillance culture program encompassed 138 randomly selected pregnant women, with five subjected to sample collection at two different time points. The clinical characterization was explored through statistical analysis. Whole-genome sequencing, a Galleria mellonella infection model, and a global database were used to investigate the genetic characterization, pathogenicity, evolutionary history, and phylogenetic relationships of the isolates. Results: Of the 41 CRAB isolates obtained, they were divided into four ClustersRS and an orphan pattern. ClusterRS 1 (n = 31), with eight complex types in pregnancy, was also the dominant ClusterRS globally, followed by ClusterRS 13 (n = 5), identified as hypervirulent KL49 CRAB, exhibiting phylogeographical specificity to Guangdong. A maternal carriage CRAB rate of 26.09% (36/138) was revealed, with half of the isolates representing novel complex types, prominently including CT3071, as the first KL7 isolates identified in Shenzhen. Both KL49 and KL7 isolates were most commonly found in the same participant, suggesting potential intraspecific competition as a possible reason for CRAB infection without carriers during pregnancy. The independent risk factors for carriers were revealed for the first time, including advanced maternal age, gestational diabetes mellitus, and Group B Streptococcus infection. Conclusion: The significant carriage rate and enhanced virulence of CRAB during pregnancy emphasize the imperative for routine surveillance to forestall dissemination within this high-risk group, especially in Guangdong for ClusterRS 13 isolates. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolations have rapidly increased in pediatric patients. To investigate a possible health care-associated infections of CRKP in a tertiary pediatric hospital, the circulating clones and carbapenem-resistant pattern between CRKP and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates were compared to classify their epidemiological characteristics. The results will help to identify the epidemic pattern of the CRKP transmission in the hospital. Methods: Ninety-six CRKP and forty-eight CRAB isolates were collected in Kunming Children's Hospital from 2019 through 2022. These isolates were genotyped using repetitive extragenic palindromic-PCR (REP-PCR). Carbapenemase phenotypic and genetic characterization were investigated using a disk diffusion test and singleplex PCR, respectively. In addition, these characteristics of the two pathogens were compared. Conclusions: These CRKP isolates exhibited different biological and genetic characteristics with dynamic changes, suggesting widespread communities. Continuous epidemiological surveillance and multicenter research should be carried out to strengthen the prevention and control of infections. [ABSTRACT FROM AUTHOR]

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration–time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP. [ABSTRACT FROM AUTHOR]

Background: The drug resistance of carbapenem-resistant Acinetobacter baumannii bloodstream infections (CRAB-BSI), especially hospital-acquired infections, has promoted their rapid and vast spread. It is necessary to use reliable methods to establish better prediction models. According to Cox proportional hazards regression, a nomogram was established. Methods: A retrospective cohort study among patients who were diagnosed with CRAB-BSI was performed from January 2020 to December 2022. Univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors regarding CRAB-BSI. Then, nomograms were used to calculate the area under the curve (AUC), C-index, and calibration curve to determine the predictive accuracy and discriminability. Decision curve analysis (DCA) was employed to further confirm the clinical effectiveness of the nomogram. Results: A total of 98 cases were included in the comparison between the 28-day mortality group consisting of 32 patients and the 28-day survival group with 66 patients. The use of cefoperazone-sulbactam was significantly higher among patients who survived than among those who died. Univariable analysis revealed that factors such as primary diagnosis, time to inadequate antimicrobial therapy, and high serum creatinine and procalcitonin (PCT) levels were more prevalent in the mortality group. However, only primary diagnosis, time to inadequate antimicrobial therapy, and high PCT levels emerged as statistically significant risk factors for death in multivariate analysis and were used to construct the nomogram. The nomogram validation exhibited excellent performance. Conclusions: The nomogram was sufficiently accurate to predict the risk and prognostic factors of CRAB-BSI, allowing for individualized clinical decisions for future clinical work. The cefoperazone-sulbactam did have an effect, but more studies are needed to interpret it. [ABSTRACT FROM AUTHOR]

ABSTRACT This study aimed to characterize carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from Jiangxi patients using whole-genome sequencing (WGS). We subjected 100 clinical CRAB strains isolated from the three local largest teaching hospitals to WGS and antimicrobial susceptibility testing. Molecular epidemiology was investigated using multilocus sequence typing, core genome multilocus typing, core genome single-nucleotide polymorphism phylogeny, and pulsed-field gel electrophoresis. The most prevalent acquired carbapenemase was blaOXA-23, predominant in all isolates (100%). Isolates belonging to the dominating international clone IC2 accounted for 92% of all isolates. International IC11 (ST164Pas/ST1418Ox) clone was found in an additional 8% (eight isolates), with seven isolates (87.5%) carrying an acquired additional blaNDM-1 carbapenemase. The oxa23-associated Tn2009, either alone or in a tandem repeat structure containing four copies of blaOXA-23, was discovered in 62% (57 isolates) of IC2. The oxa23-associated Tn2006 was identified in 38% (35 isolates) of IC2 and all IC11 isolates. A putative conjugative RP-T1 (formerly RepAci6) plasmid with blaOXA-23 in Tn2006 within AbaR4, designated pSRM1.1, was found in IC2 A. baumannii strain SRM1. The blaNDM-1 gene found in seven IC11 isolates was located on a novel Tn6924-like transposon, a first-time report in IC11. These findings underscore the significant importance of real-time surveillance to prevent the further spread of CRAB.IMPORTANCECarbapenem-resistant Acinetobacter baumannii (CRAB) is notorious for causing difficult-to-treat infections. To elucidate the molecular and clinical epidemiology of CRAB in Jiangxi, clinical CRAB isolates were collected and underwent whole-genome sequencing and antibiotic susceptibility phenotyping. Key findings included the predominance of OXA-23-producing IC2 A. baumannii, marked by the emergence of OXA-23 and NDM-1-producing IC11 strains.

A carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak in an intensive care unit (ICU) was contained by an improved infection-control measure that included a disinfectant policy. In our retrospective cohort study, we describe the epidemiological investigations and infection-control measures during this outbreak. Descriptive analysis was used to summarize patient demographics, neurological diseases, surgical treatment, underlying diseases, infection, and outcomes. In December 2023, two CARB-positive patients were observed in the ICU, and four more patients became CRAB-positive in January. During this outbreak, there was an overlap of hospitalization periods among the CRAB-positive patients, and CRAB was isolated from the environment; the isolated CRAB strain was identical. Infection-control measures, including hand hygiene, contact precautions and isolation, surveillance, decolonization, environmental cleaning, and disinfection, were reviewed and modified. The aim of this study was to examine the molecular background of the effectiveness of the disinfectant shift used during successful outbreak control. Experiments were carried out to study the phenotypic sensitivity and genetic background of different disinfectant agents. A thorough analysis of the detected CRAB strain included whole-genome sequencing (WGS), investigation of the qacE and qacEΔ1 genes’ relative expression by qPCR after exposure to different disinfectant solutions, as well as an analysis of biofilm formation. WGS analysis of the CRAB strain identified that an ST2 high-risk clone was responsible for the outbreak, which produced OXA-83 and ADC-30 beta-lactamases; in addition, qacE and qacEΔ1 genes were also detected, which confer resistance to disinfectants containing quaternary ammonium compounds (QACs). A qPCR analysis demonstrated that after exposure to different disinfectants, the gene expression levels of qacE and qacEΔ1 increased and correlated with concentrations of QACs of disinfectants. During the outbreak, the standard-of-care QAC-based disinfectant was changed to a mainly alcohol-based agent in the ICU, which contributed to the successful control of this outbreak, and no additional patients were identified with CRAB. We conclude that continuous surveillance and hand hygiene training combined with fast identification and reaction to new cases, as well as an in-depth analysis of multidrug-resistant outbreak strains and investigation of their disinfectant tolerance/resistance during an outbreak, are essential to effectively control the spread of nosocomial pathogens. The smart policy of disinfectant agent selection played a crucial role in controlling the outbreak and ensuring patient safety in the ICU.

OBJECTIVE: To probe into the efficacy of cefoperazone sulbactam respectively combined with moxifloxacin and imipenem cilastatin in the treatment of carbapenem-resistant Acinetobacter baumannii ( CRAB) pneumonia and its effects on inflammatory reaction. METHODS: Data of 80 patients with CRAB pneumonia admitted into the hospital from Jan. 2022 to Jun. 2023 were retrospectively analyzed, 40 cases from Jan. to Sept. 2022 were selected via convenience sampling method to be set as group A, which was given cefoperazone sulbactam combined with moxifloxacin; 40 cases from Oct. 2022 to Jun. 2023 were selected via convenience sampling method to be set as group B, which was given cefoperazone sulbactam combined with imipenem cilastatin. The efficacy, bacterial clearance effect, recovery time of various indicators, indicators of serum inflammation and incidences of adverse drug reactions (ADR) were compared between two groups. RESULTS: The total effective rate and the bacterial clearance rate of group B were respectively 95. 00% ( 38 / 40) and 90. 00% ( 36 / 40), significantly higher than 80. 00% (32 / 40) and 72. 50% (29 / 40) of group A, with statistically significant differences (P<0. 05). The recovery time of chest CT, time of fever remission and recovery time of white blood cell count of group B were shorter than those of group A, with statistically significant differences (P<0. 05). After 2 weeks of treatment, the serum tumor necrosis factor α (TNF-α), procalcitonin (PCT) and interleukin 6 (IL-6) levels of both groups were lower than those before treatment, the TNF-α, PCT and IL-6 levels of group B were lower than those of group A, with statistically significant differences (P<0. 05). The incidence of ADR was 12. 50% (5 / 40) in group B and 17. 50% (7 / 40) in group A, the difference was not statistically significant ( P > 0. 05 ). CONCLUSIONS: The efficacy of cefoperazone sulbactam combined with imipenem cilastatin in the treatment of CRAB pneumonia is better than that of cefoperazone sulbactam combined with moxifloxacin, which can effectively improve patients inflammation, obviously promote bacterial clearance effect, significantly short the recovery time of temperature, white blood cell count and other indicators, with few ADR. [ABSTRACT FROM AUTHOR]

To the best of our knowledge, to date, no study has investigated the optimal dosage regimens of either colistin or sitafloxacin against drug-resistant Acinetobacter baumannii (A. baumannii) infections by using specific parameters. In the current study, we aimed to explore the optimal dosage regimens of colistin and sitafloxacin, either in monotherapy or in combination therapy, for the treatment of carbapenem-, multidrug-, and colistin-resistant A. baumannii infections. A Monte Carlo simulation was applied to determine the dosage regimen that could achieve the optimal probability of target attainment (PTA) and cumulative fraction of response (CFR) (=90%) based on the specific parameters of each agent and the minimal inhibitory concentration (MIC) of the clinical isolates. This study explored the dosage regimen of 90, 50, 30, and 10 mL/min for patients with creatinine clearance (CrCL). We also explored the dosage regimen for each patient with CrCL using combination therapy because there is a higher possibility of reaching the desired PTA or CFR. Focusing on the MIC90 of each agent in combination therapy, the dosage regimen for colistin was a loading dose of 300 mg followed by a maintenance dose ranging from 50 mg every 48 h to 225 mg every 12 h and the dosage regimen for sitafloxacin was 325 mg every 48 h to 750 mg every 12 h. We concluded that a lower-than-usual dose of colistin based on specific pharmacokinetic data in combination with a higher-than-usual dose of sitafloxacin could be an option for the treatment of carbapenem-, multidrug-, and colistinresistant. A. baumannii. The lower dose of colistin might show a low probability of adverse reaction, while the high dose of sitafloxacin should be considered. In the current study, we attempted to find if there is a strong possibility of drug selection against crucial drug-resistant pathogen infections in a situation where there is a lack of new antibiotics. However, further study is needed to confirm the results of this simulation study. [ABSTRACT FROM AUTHOR]

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain a clinical challenge due to limited treatment options. Recently, cefiderocol, a novel siderophore cephalosporin, and sulbactam-durlobactam, a bactericidal β-lactam–β-lactamase inhibitor combination, have been approved by the Food and Drug Administration for the treatment of A. baumannii infections. In this review, we discuss the mechanisms of action of and resistance to cefiderocol and sulbactam-durlobactam, the antimicrobial susceptibility of A. baumannii isolates to these drugs, as well as the clinical effectiveness of cefiderocol and sulbactam/durlobactam-based regimens against CRAB. Overall, cefiderocol and sulbactam-durlobactam show an excellent antimicrobial activity against CRAB. The review of clinical studies evaluating the efficacy of cefiderocol therapy against CRAB indicates it is non-inferior to colistin/other treatments for CRAB infections, with a better safety profile. Combination treatment is not associated with improved outcomes compared to monotherapy. Higher mortality rates are often associated with prior patient comorbidities and the severity of the underlying infection. Regarding sulbactam-durlobactam, current data from the pivotal clinical trial and case reports suggest this antibiotic combination could be a valuable option in critically ill patients affected by CRAB infections, in particular where no other antibiotic appears to be effective. [ABSTRACT FROM AUTHOR]

ABSTRACTTimely detection of carbapenem-resistant Acinetobacter baumannii (CRAB) carriers is essential to direct infection control measures. In this work, we aimed to develop a practical protocol to detect CRAB from screening samples. To choose a selective medium that detects CRAB with high sensitivity and specificity, 111 A. baumannii clinical isolates were inoculated on three types of agar: mSuperCARBA (SC), CHROMagar Acinetobacter (CaA), and modified CHROMagar Acinetobacter (mCaA) containing 4.5 mg/mL meropenem. SC was non-selective, CaA was the most sensitive (100%), but only moderately specific (72%), and mCaA was highly specific (97%) and sensitive (98%). Confirmation of the carbapenem-resistant phenotype using PCR-based detection of blaOXA-23, blaOXA-24, and blaOXA-58 genes was specific but not sensitive, detecting only 58% of CRAB isolates. Identification of A. baumannii using either gyrB or blaOXA-51 PCR was excellent. Next, we used the same methodology in routine screening for CRAB carriage. mCaA had the best yield, with high sensitivity but moderate specificity to differentiate between CRAB and other carbapenem-resistant organisms. Skin sampling using sponges and 6 hour enrichment was highly sensitive (98%), while other body sites had poor sensitivity (27%– 41%). Shorter incubation had slightly lower yield, and longer incubation did not improve the detection. Performing PCR for blaOXA-51 and gyrB on colonies growing on modified mCaA differentiated between CRAB and other species with high accuracy (98% and 99%, respectively). Based on our results, we present a procedure for easy and reliable detection of CRAB carriage using skin sampling, short enrichment, selection on mCaA, and PCR-based identification.IMPORTANCECarbapenem-resistant Acinetobacter baumannii (CRAB) is a substantial cause of nosocomial infections, classified among the most significant multidrug-resistant pathogens by the World Health Organization and by the US Centers for Disease Control. Limiting the spread of CRAB is an important goal of infection control, but laboratory methods for identification of CRAB carriers are not standardized. In this work, we compared different selective agar plates, tested the efficiency of A. baumannii identification by PCR for species-specific genes, and used PCR-based detection of common resistance genes to confirm the carbapenem-resistant phenotype. During a prospective study, we also determined the optimal sample enrichment time. Based on our results, we propose a simple and efficient protocol for the detection of CRAB carriage using skin sampling, short enrichment, selection on appropriate agar plates, and PCR-based identification, resulting in a turn-around time of 24 hours.

Purpose: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an urgent concern to public health. This study focuses on exploring the resistance mechanisms and the in vitro results of using rifampicin in combination with conventional antibiotics for the management of CRAB. Methods: The synergistic and bactericidal effects of rifampicin with conventional antibiotics were evaluated using chequerboard assay and time-kill assay, while the phenotypic and genotypic characteristics of resistant determinants were performed by efflux pump detection and whole genome sequencing on 29 isolates from ICU patients with underlying health diseases. Results: The isolates showed multidrug resistance, with over 60% showing addictive responses to rifampicin-based combinations at FICI ranging from 0.6 to 0.8. The time-kill assay revealed 99 % killing for rifampicin and minocycline combination in one isolate at 1/4 MIC rifampicin plus 1/4 MIC minocycline, while a bacteriostatic effect was observed at 1/2 MIC rifampici plus 1/2 MIC for a second isolate. Combination with tigecycline resulted in a 99% killing in two out of three isolates with a 2.5–3 log reduction in CFU at 1/4 MIC rifampicin plus 1/4 MIC tigecycline. Rifampicin plus colistin exhibited bactericidal activity against three out of four isolates. The combinations of rifampicin with ciprofloxacin, chloramphenicol, and trimethoprim-sulfamethoxazole were ineffective against the isolates. In addition, a 4-fold reduction in rifampicin MIC was observed in 2 out of 14 isolates in the presence of an efflux pump inhibitor. The pan-genome study demonstrated a progressive evolution with an accessory genome estimated to cover 58% of the matrix. Seven of the ten sequenced isolates belong to sequence type 2 (ST2), while one isolate each was assigned to ST164, ST16, and ST25. Furthermore, 11 plasmids, 34 antimicrobial resistance (AMR) genes, and 65 virulence-associated genes were predicted from the whole genome data. The blaOXA-23 blaADC-25, blaOXA-66, blaPER-7, aph(6)-Id, armA, and arr-3 were prevalent among the isolates. Sequence alignment of the bacteria genome to the reference strain revealed a deleterious mutation in the rpoB gene of 4 isolates. Conclusion: The study suggests that rifampicin in combination with either minocycline, tigecycline, or colistin might be a treatment option for CRAB clinical isolates. In addition, genotypic analysis of the bacteria isolates may inform the clinician of the suitable drug regimen for the management of specific bacteria variants.

Abstract Introduction Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with high mortality with limited treatment. The aim of this study is to compare effectiveness and safety of colistin-based versus cefiderocol-based therapies for CRAB-BSI. Methods This is a retrospective observational study enrolling patients with monomicrobial CRAB-BSIs treated with colistin or cefiderocol from 1 January 2020, to 31 December 2022. The 30-day all-cause mortality rate was the primary outcome. A Cox regression analysis was performed to identify factors independently associated with mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. Results Overall 118 patients were enrolled, 75 (63%) and 43 (37%) treated with colistin- and cefiderocol-based regimens. The median (q1–q3) age was 70 (62–79) years; 70 (59%) patients were men. The 30-day all-cause mortality was 52%, significantly lower in the cefiderocol group (40% vs 59%, p = 0.045). By performing a Cox regression model, age (aHR = 1.03, 95% CI 1.00–1.05), septic shock (aHR = 1.93, 95% CI 1.05–3.53), and delayed targeted therapy (aHR = 2.42, 95% CI 1.11–5.25) were independent predictors of mortality, while cefiderocol-based therapy was protective (aHR = 0.49, 95% CI 0.25–0.93). The IPTW-adjusted Cox analysis confirmed the protective effect of cefiderocol (aHR = 0.53, 95% CI 0.27–0.98). Conclusions Cefiderocol may be a valuable treatment option for CRAB-BSI, especially in the current context of limited treatment options.

We investigated the activity of cefiderocol/β-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most “Critical Priority” group of MDR bacteria (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log10 CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii; of the cefiderocol/avibactam combination against carbapenem-resistant Enterobacterales; and of the cefiderocol/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all β-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol/avibactam was only active against carbapenem-resistant Enterobacterales.

Acinetobacter baumannii is a challenging multidrug-resistant pathogen in healthcare. Phage vB_AbaSi_W9 (GenBank: PP146379.1), identified in our previous study, shows lytic activity against 26 (89.66%) of 29 carbapenem-resistant Acinetobacter baumannii (CRAB) strains with various sequence types (STs). It is a promising candidate for CRAB treatment; however, its lytic efficiency is insufficient for complete bacterial lysis. Therefore, this study aimed to investigate the clinical utility of the phage vB_AbaSi_W9 by identifying antimicrobial agents that show synergistic effects when combined with it. The A. baumannii ATCC17978 strain was used as the host for the phage vB_AbaSi_W9. Adsorption and one-step growth assays of the phage vB_AbaSi_W9 were performed at MOIs of 0.001 and 0.01, respectively. Four clinical strains of CRAB belonging to different sequence types, KBN10P04948 (ST191), LIS2013230 (ST208), KBN10P05982 (ST369), and KBN10P05231 (ST451), were used to investigate phage–antibiotic synergy. Five antibiotics were tested at the following concentration: meropenem (0.25–512 µg/mL); colistin, tigecycline, and rifampicin (0.25–256 µg/mL); and ampicillin/sulbactam (0.25/0.125–512/256 µg/mL). The in vitro synergistic effect of the phage and rifampicin was verified through an in vivo mouse infection model. Phage vB_AbaSi_W9 demonstrated 90% adsorption to host cells in 1 min, a 20 min latent period, and a burst size of 114 PFU/cell. Experiments combining phage vB_AbaSi_W9 with antibiotics demonstrated a pronounced synergistic effect against clinical strains when used with tigecycline and rifampicin. In a mouse model infected with CRAB KBN10P04948 (ST191), the group treated with rifampicin (100 μg/mL) and phage vB_AbaSi_W9 (MOI 1) achieved a 100% survival rate—a significant improvement over the phage-only treatment (8.3% survival rate) or antibiotic-only treatment (25% survival rate) groups. The bacteriophage vB_AbaSi_W9 demonstrated excellent synergy against CRAB strains when combined with tigecycline and rifampicin, suggesting potential candidates for phage–antibiotic combination therapy in treating CRAB infections.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. Methods: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. Results: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. Conclusions: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.

Carbapenem-resistant Acinetobacter baumannii (CR-AB) is rarely found in community respiratory infections, and there are currently no reports of hemorrhagic bronchitis caused by its infection. This work presents a case of bronchial bleeding in a diabetic patient who acquired a community-acquired infection of CR-AB. Treatment with levofloxacin was unsuccessful, as the patient's hemoptysis symptoms recur. The patient was treated with minocycline based on the drug sensitivity test, resulting in the disappearance of hemoptysis symptoms. The patient was subjected to follow-up by phone for three months and did not experience any further hemoptysis symptoms. This case highlights that CR-AB infection causes hemorrhagic bronchitis, and the antimicrobial treatment should be based on drug sensitivity results.

ABSTRACT Carbapenem-resistant Acinetobacter baumannii spp. are increasingly important pathogens with limited treatment options, and there is limited knowledge on the environmental factors contributing to their spread. We determined the occurrence of carbapenem-resistant A. baumannii in hospital wastewater and their phylogenetic relationships with clinical A. baumannii isolates. Grab samples of raw and treated hospital wastewater were collected monthly at the University College Hospital, Ibadan, Nigeria, between March 2021 and February 2022. Acinetobacter baumannii strains were selectively isolated and identified using VITEK2, and their whole genomes were sequenced on an Illumina platform. We performed antimicrobial susceptibility testing and in silico genomic characterization of the strains and determined their phylogenetic relationships to previously characterized clinical A. baumannii strains from Nigeria. A. baumannii complex isolates were recovered from wastewater throughout the study. Of the 82 isolates identified based on whole-genome sequences, 77 were A. baumannii. A. baumannii isolates had high resistance rates (≥48.1%) to 10 of 12 antimicrobials tested, and majority (42/77, 54.5%) were resistant to carbapenems, with bla NDM-1 being the most common (24/77, 31.2%) carbapenem resistance gene detected, followed by bla OXA-23 (n = 22, 28.6%). There was no statistically significant difference in carbapenem resistance rates or carbapenem gene carriage between the raw and treated wastewater isolates. Most of the isolates belonged to novel or sparsely described lineages, some of which were closely related to clinical isolates. The release of inadequately treated hospital wastewater into the environment may contribute to the increased spread of carbapenem-resistant and clinically important A. baumannii lineages in Ibadan, Nigeria. IMPORTANCE Acinetobacter baumannii is a leading cause of hospital-associated infections globally. A. baumannii reservoirs outside hospital settings are still unknown, and their occurrence in the environment is linked to clinical and anthropogenic activities. Although the risk of transmission of A. baumannii from environmental sources to humans is not fully understood, these sources pose significant risks for the continued dissemination of A. baumannii and their resistance traits. This study provides evidence that diverse and clinically relevant A. baumannii strains, many of which are resistant to carbapenems, are constantly being discharged into the environment through inadequately treated hospital wastewater. We further elucidate potential transmission routes between the environment and clinical infections and demonstrate the high prevalence of carbapenem resistance genes on highly mobile transposons among these strains. Our findings highlight the pressing need to address hospital wastewater as a crucial factor in curtailing the spread of carbapenem-resistant A. baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a well-known harmful bacterium that causes severe health disorders and dysregulates the host immune response associated with inflammation. Upon examining the suppressive activity of natural flavonoid rhamnetin on various pro-inflammatory cytokines in a CRAB-induced septic shock mouse model, we found that rhamnetin inhibited the production of IL-1β and IL-18, two pro-inflammatory cytokines associated with pyroptotic cell death, a process dependent on caspase-1. In this study, we investigated the antioxidant and anti-apoptotic activities of rhamnetin and the underlying mechanism of action in a CRAB infection. In the CRAB-induced septic shock mouse model, rhamnetin reduced the level of lipopolysaccharide (LPS) in lung lysates, resulting in the inhibition of TLR4-mediated inflammatory signaling. Notably, rhamnetin reduced intracellular reactive oxygen species (ROS) generation in macrophages and inhibited apoptotic and pyroptotic cell injury induced by CRAB infection. Therefore, rhamnetin inhibited LPS-induced pro-inflammatory mediators, hindering apoptotic and pyroptotic processes and contributing to a recovery effect in CRAB-induced sepsis mice by suppressing oxidative stress. Taken together, our study presents the potential role of rhamnetin in protecting against oxidative damage induced by CRAB infection through a TLR4 and ROS-mediated pyroptotic pathway, showing an alternative mechanism for sepsis prevention. Therefore, rhamnetin is a promising therapeutic candidate for treating CRAB-induced sepsis. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Acinetobacter baumannii (CRAB) strains can cause severe and difficult-to-treat infections in patients with compromised general health. CRAB strains disseminate rapidly in nosocomial settings by patient-to-patient contact, through medical devices and inanimate reservoirs. The occurrence of CRAB in patients residing in the intensive care units (ICUs) of the Sahloul University hospital in Sousse, Tunisia is high. The objective of the current study was to determine whether the surfaces of items present in five ICU wards and the medical personnel there operating could serve as reservoirs for CRAB strains. Furthermore, CRAB isolates from patients residing in the ICUs during the sampling campaign were analyzed for genome comparison with isolates from the ICUs environment. Overall, 206 items were screened for CRAB presence and 27 (14%) were contaminated with a CRAB isolate. The items were located in several areas of three ICUs. Eight of the 54 (15%) screened people working in the wards were colonized by CRAB on the hands. Patients residing in the ICUs were infected with CRAB strains sharing extensive genomic similarity with strains recovered in the nosocomial environment. The strains belonged to three sub-clades of the internationally disseminated clone (ST2). A clone emerging in the Mediterranean basin (ST85) was detected as well. The strains were OXA-23 or NDM-1 producers and were also pan-aminoglycoside resistant due to the presence of the armA gene. Hygiene measures are urgent to be implemented in the Sahloul hospital to avoid further spread of difficult-to-treat CRAB strains and preserve health of patients and personnel operating in the ICU wards. [ABSTRACT FROM AUTHOR]

Background and Objectives: Health care-associated infections (HAI) are one of the most common adverse events in health-care delivery and an endemic burden as major health-care problem. Carbapenems have broad-spectrum antibacterial activity and thus known as Extended-spectrum ß-lactamases. Therefore, the emergence of carbapenem-resistant bacteria poses great significance in HAI. Methods: The study was undertaken to see the prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant enterobacteriaceae (CRE) in patient samples and surrounding environment. During the study, all the patients' clinical samples sent to the microbiology department for culture sensitivity were considered. All isolates were processed according to standard microbiological protocols and reported according to the Clinical and Laboratory Standards Institute guidelines. Environmental swabs were taken from HI-touch areas from all intensive care unit (ICU)-admitted patients' rooms. Results: Around 290 isolates were reported during the study from concerned ICUs. Out of which 80 samples were carbapenemase producers. Environmental samples were collected from ICUs from Hi-Touch areas showed growth in 23 samples out of a total of 270. Carbapenem-resistant isolates identified in the study belonged equally to Enterobacteriaceae (most common-Klebsiella pneumoniae and Escherichia coli) and nonfermenters classes (CRAB and Pseudomonas aeruginosa), were of similar concern and also difficult to treat, and further compounds the morbidity and mortality of associated infections. The majority of carbapenem-resistant pathogens in this study were resistant to extended-spectrum cephalosporins, fluoroquinolones, and piperacillin-tazobactam (multidrug-resistant [MDR]). Interpretation and Conclusions: In a setting where CRE and CRAB persist, environmental contamination is common. Screening of patients, ensuring strict contact precautions, and strictly following decontamination guidelines in ICUs can be a powerful tool in discerning HAI caused due to CRE and CRAB. [ABSTRACT FROM AUTHOR]

The present study determined the effect of untreated wastewater on the prevalence of carbapenem resistance in Acinetobacter baumannii (CRAB) in both the wastewater and the receiving river water surrounding Cuttack City. Physiochemical parameters, heavy metal contamination factors (CF), contamination degree (CD), pollution load index (PLI), and microbiological content (total coliform, fecal form, and CRAB) were analyzed in two untreated urban wastewater and three in receiving river water (upstream, catchment, and downstream). The high BOD, CF, CD, and PLI in urban wastewater, river catchment, and downstream revealed intense anthropogenic activity. After blaOXA-51 detection and clonal analysis by ERIC-PCR, a total of 73 CRAB were selected for further analysis. All the CRAB isolates were 100% resistant to penicillin, β-lactam/β-lactamase inhibitor, cephalosporin, and carbapenem groups of antibiotics. The antibiotic profile showed 73.97% CRAB isolates assigned as extremely drug resistant. Detection of carbapenemase (blaNDM and blaOXA-48) and co-harboring ESBL (blaTEM) genes, the highest at the river, reflects direct disposal of biomedical wastes. MAR index (> 0.2) and virulence index (> 0.5) in 59 isolates were classified as a high threat posing a severe human risk. A similar ERIC pattern between the isolates from two different locations (catchment and downstream) indicates their dissemination downstream through river water flow. The extraordinary ability of resistant A. baumannii to thrive in the river makes it unfit for household activities and poses a public health threat. Therefore, frequent monitoring of resistance levels in water could help direct antibiotic use and resistance management. [ABSTRACT FROM AUTHOR]

Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration–time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP.

Background and aimsCarbapenem-resistant Acinetobacter baumannii (CRAB) has become a leading cause of nosocomial infections with an increasing impact on critically ill patients, yet there is limited data on contributing factors. This study was aim to evaluate the prevalence and risk factors, and clinical outcomes of CRAB infections among critically ill children in a tertiary university teaching hospital in China.MethodsFrom January 2016 to December 2021, all children diagnosed with nosocomial Acinetobacter baumannii (A. baumannii) infections in the pediatric intensive care unit (PICU) were identified through the computerized microbiology laboratory databases. Among them, children suffering from CRAB infection were designated as a case group, while children with carbapenem susceptible A. baumannii (CSAB) infection were assigned to a control group. This retrospective case-control study was based on two groups of patients to determine potential clinical factors contributing to CRAB infection and death among critically ill children via univariate and multivariate analyses.ResultsDuring the 6-year study period, a total of 372 episodes of nosocomial A. baumannii infection in the PICU were eligible and included in the study. These isolates displayed moderate or high rates of resistance to all tested antimicrobials except colistin. The overall prevalence of CRAB and MDRAB (multidrug-resistant A. baumannii) was 78.0% and 80.9%, respectively. Several risk factors found to significantly increase CRAB infection included receiving invasive operation (OR = 9.412, p = 0.001), gastric intubation (OR = 2.478, p = 0.026), prior carbapenems exposure (OR = 2.543, p = 0.003), severe pneumonia (OR = 3.235, p = 0.001), and hemoglobin 46U/L (OR = 2.015, p = 0.005), bone marrow aspiration (OR = 2.704, p = 0.008), lymphocyte