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Due to its antimicrobial resistance characteristics, the World Health Organization (WHO) classifies A. baumannii as one of the critical priority pathogens for the development of new therapeutic strategies. Vaccination has been approached as an interesting strategy to overcome the lack of effective antimicrobials and the long time required to develop and approve new drugs. In this study, we aimed to evaluate as a vaccine the hypothetical adhesin protein CAM87009.1 in its recombinant format (rCAM87009.1) associated with aluminum hydroxide (Alhydrogel®) or biogenic silver nanoparticles (bio-AgNP) as adjuvant components against lethal infection by A. baumannii MDR strain. Both vaccine formulations were administered in three doses intramuscularly in BALB/c murine models and the vaccinated animals were tested in a challenge assay with A. baumannii MDR strain (DL 100). rCAM87009.1 protein associated with both adjuvants was able to protect 100 % of animals challenged with the lethal strain during the challenge period. After the euthanasia of the animals, no A. baumannii colonies were detected in the lungs of animals vaccinated with the rCAM87009.1 protein in both formulations. Since the first immunization, high IgG antibody titers were observed (1:819,200), with results being statistically similar in both vaccine formulations evaluated. rCAM87009.1 associated with both adjuvants was capable of inducing at least one class of isotypes associated with the processes of neutralization (IgG2b and IgA for bio-AgNP and Alhydrogel®, respectively), opsonization (IgG1 in both vaccines) and complement activation (IgM and IgG3 for bio-AgNP and Alhydrogel®, respectively). Furthermore, reduced tissue damage was observed in animals vaccinated with rCAM87009.1 + bio-AgNP when compared to animals vaccinated with Alhydrogel®. Our results indicate that the rCAM87009.1 protein associated with both bio-AgNP and Alhydrogel® are combinations capable of promoting immunity against infections caused by A. baumannii MDR. Additionally, we demonstrate the potential of silver nanoparticles as alternative adjuvant molecules to the use of aluminum salts. [ABSTRACT FROM AUTHOR]

Objective Late-onset sepsis (LOS) is a substantial contributor to morbidity and mortality among neonates. The use of nonculture-based tools for early diagnosis is an area of active investigation. Therefore, we aimed to evaluate the diagnostic value of serum interleukin-27 (IL-27) and mean platelet volume (MPV) in full-term neonates with LOS. Study Design In this single-center, cross-sectional study, 90 full-term newborns were assigned to two equal-matched groups as follows: (1) culture-proven sepsis and (2) control groups. Clinical data and laboratory findings as complete blood pictures, including MPV, highly sensitive C-reactive protein, and blood culture results, were recorded. Moreover, IL-27 levels were measured using enzyme-linked immunosorbent assay. Results IL-27 levels (median = 4,364 pg/mL) and MPV (mean = 12.02 ± 1.54 FL) were significantly higher in the culture-proven sepsis group than in the control group (p < 0.001). For IL-27, the optimum cut-off value for the diagnosis of LOS was 283.8 pg/mL with sensitivity and specificity of 97.8 and 100%, respectively. For MPV, the optimum cut-off value was 11.6 FL, with diagnostic sensitivity and specificity of 77.8 and 97.8%, respectively. Conclusion IL-27 and MPV are promising markers for the diagnosis of LOS in full-term neonates. The diagnostic performance of IL-27 was superior to MPV. Key Points Late-onset neonatal sepsis diagnosis is time consuming. Nonculture-based rapid diagnostic tests are much needed. IL-27 is superior in LOS diagnosis to MPV. [ABSTRACT FROM AUTHOR]

This article evaluates the use of an artificial intelligence tool called ChatGPT in the field of respiratory medicine. ChatGPT is designed to provide human-like responses to a wide range of topics, including medical inquiries. However, there are concerns about its accuracy and reliability in the medical sector, as it has not been extensively trained with biomedical datasets or vetted by medical professionals. The study found that ChatGPT provided correct answers for 63.5% of respiratory medicine questions, with higher accuracy in basic medical knowledge and lower accuracy in treatment and management. It is important to note that ChatGPT should not replace professional medical advice and should be used with caution. The article highlights the limitations of ChatGPT and suggests that it can be used as a supplementary educational tool under expert guidance. Future research should focus on improving the model's accuracy and reliability in specialized domains like respiratory medicine. [Extracted from the article]

Objective: This study aimed to develop and apply a nomogram with good accuracy to predict the risk of CRAB infections in neuro-critically ill patients. In addition, the difficulties and expectations of application such a tool in clinical practice was investigated. Methods: A mixed methods sequential explanatory study design was utilized. We first conducted a retrospective study to identify the risk factors for the development of CRAB infections in neuro-critically ill patients; and further develop and validate a nomogram predictive model. Then, based on the developed predictive tool, medical staff in the neuro-ICU were received an in-depth interview to investigate their opinions and barriers in using the prediction tool during clinical practice. The model development and validation is carried out by R. The transcripts of the interviews were analyzed by Maxqda. Results: In our cohort, the occurrence of CRAB infections was 8.63% (47/544). Multivariate regression analysis showed that the length of neuro-ICU stay, male, diabetes, low red blood cell (RBC) count, high levels of procalcitonin (PCT), and number of antibiotics ≥ 2 were independent risk factors for CRAB infections in neuro-ICU patients. Our nomogram model demonstrated a good calibration and discrimination in both training and validation sets, with AUC values of 0.816 and 0.875. Additionally, the model demonstrated good clinical utility. The significant barriers identified in the interview include "skepticism about the accuracy of the model", "delay in early prediction by the indicator of length of neuro-ICU stay", and "lack of a proper protocol for clinical application". Conclusions: We established and validated a nomogram incorporating six easily accessed indicators during clinical practice (the length of neuro-ICU stay, male, diabetes, RBC, PCT level, and the number of antibiotics used) to predict the risk of CRAB infections in neuro-ICU patients. Medical staff are generally interested in using the tool to predict the risk of CRAB, however delivering clinical prediction tools in routine clinical practice remains challenging. [ABSTRACT FROM AUTHOR]

Multidrug resistance patterns of Acinetobacter spp. have led to their emergence as an important source of nosocomial infections. This study investigated the prevalence and clinical characteristics of Acinetobacter spp. in hospital-acquired wound and urinary tract infections. A total of 432 samples [wound swabs (210) and urine samples (222)] were analyzed for the presence of Acinetobacter spp. through selective culturing on MacConkey and Leeds Acinetobacter medium followed by identification with API 20E strips and VITEK 2 compact system. Antimicrobial susceptibility was assessed by adopting the disk diffusion method on Muller-Hinton agar, whereas the minimum inhibitory concentration procedure was carried out by using a ComASP™ Colistin test kit. Biofilm formation was examined using microtiter plates and following the crystal violet staining method. PCR was performed to amplify virulence (lasB, bap, and plcN) and antimicrobial resistance (blaOXA-51like) genes. The results revealed a low prevalence of Acinetobacter spp. (1.85 %) where Acinetobacter baumannii was the predominant species. Acinetobacter baumannii isolates harbored blaOXA-51-like gene to exert extensive or pan-drug resistance. Most Acinetobacter baumannii isolates demonstrated weaker to moderate biofilm-forming capabilities and carried the bap gene. Acinetobacter baumannii isolates lacked the combination of virulence factors encoding lasB and plcN genes. Acinetobacter baumannii infections are rising in Saudi Arabia. The results of this study highlight the epidemiology of virulent and antibiotic-resistant Acinetobacter spp., particularly A. baumannii, in Saudi Arabia. The detailed elaboration on the diversity, virulence, and antimicrobial susceptibility patterns of Acinetobacter spp. in Saudi Arabia requires further in-depth molecular investigations. [ABSTRACT FROM AUTHOR]

Background: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. Results: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20–40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. Conclusions: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development. [ABSTRACT FROM AUTHOR]

Background: Ventilator-associated pneumonia (VAP) is defined as infection of lung parenchyma in patients exposed to invasive mechanical ventilation for at least 48 h. VAP is the second most common hospital-acquired infection with a mortality rate up to 40%. Aims and Objectives: To determine the microbiological profile of VAP-related samples, the demographic profile of patients, and associated risk factors. Materials and Methods: VAPrelated samples including endotracheal tube tip, tracheal secretions, and bronchoalveolar lavage (BAL) fluid were collected from 73 patients during the study period from January 2023 to November 2023. Their blood samples were also collected for automated blood culture. Samples were processed as per standard protocol. Results: Out of the total patients, 60.31% were male and 39.68% were female. 61-80 years was the most commonly affected age group. The most commonly isolated micro-organism was Acinetobacter baumannii with the highest sensitivity to polymixin B and tigecycline. Associated blood culture positivity was maximum in patients whose samples of ET tube tip, tracheal secretions, and BAL fluid had isolated A. baumannii and Klebsiella pneumoniae. Two Candida albicans were isolated with sensitivities to voriconazole and amphotericin B. Many patients had associated septicemia. Endotracheal intubation and tracheal suction were the most common risk factors associated. Conclusion: As associated septicemia may increase the mortality rate manifold blood samples should also be collected in suspected VAP patients along with VAP-related samples for early detection of sepsis leading to better patient management. [ABSTRACT FROM AUTHOR]

Introduction Combat-related wound infections complicate the recovery of wounded military personnel, contributing to overall morbidity and mortality. Wound infections in combat settings present unique challenges because of the size and depth of the wounds, the need to administer emergency care in the field, and the need for subsequent treatment in military facilities. Given the increase in multidrug-resistant pathogens, a novel, broad-spectrum antibiotic is desired across this continuum of care when the standard of care fails. Omadacycline was FDA-approved in 2018 for treatment of adults with acute bacterial skin and skin structure infections (ABSSSI), as well as community-acquired bacterial pneumonia (CABP). It is a broad-spectrum antibiotic with activity against gram-positive, gram-negative, and atypical bacterial pathogens, including multidrug-resistant species. Omadacycline can overcome commonly reported tetracycline resistance mechanisms, ribosomal protection proteins, and efflux pumps, and is available in once-daily intravenous or oral formulations. In this review, we discuss the potential role of omadacycline, which is included in the Department of Defense Formulary, in the context of combat wound infections. Materials and Methods A literature review was undertaken for manuscripts published before July 21, 2023. This included a series of publications found via PubMed and a bibliography made publicly available on the Paratek Pharmaceuticals, Inc. website. Publications presenting primary data published in English on omadacycline in relation to ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli , and Enterobacter species) pathogens and Clostridioides difficile, including in vitro, in vivo , and clinical data were included. Results Of 260 identified records, 66 were included for evidence review. Omadacycline has in vitro activity against almost all the ESKAPEE pathogens, apart from P. aeruginosa. Importantly, it has activity against the four most prevalent bacterial pathogens that cause wound infections in the military healthcare system: S. aureus , including methicillin-resistant S. aureus, A. baumannii, K. pneumoniae , and E. coli. In vivo studies in rats have shown that omadacycline is rapidly distributed in most tissues, with the highest tissue-to-blood concentration ratios in bone mineral. The clinical efficacy of omadacycline has been assessed in three separate Phase 3 studies in patients with ABSSSI (OASIS-1 and OASIS-2) and with CABP (OPTIC). Overall, omadacycline has an established safety profile in the treatment of both ABSSSI and CABP. Conclusions Omadacycline has broad-spectrum activity, the option to be orally administered and an established safety profile, making it a potentially attractive replacement for moxifloxacin in the military individual first aid kit, especially when accounting for the increasing resistance to fluoroquinolones. Further studies and clinical evaluation are warranted to support broader use of omadacycline to treat combat wound infections in the military healthcare system. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii has developed multiple drug resistances, posing a significant threat to antibiotic efficacy. LysECD7, an endolysin derived from phages, could be a promising therapeutic agent against multi-drug resistance A. baumannii. In this study, in order to further enhance the antibacterial efficiency of the engineered LysECD7, a few lipopolysaccharide-interacting peptides (Li5, MSI594 and Li5-MSI) were genetically fused with LysECD7. Based on in vitro antibacterial activity, the fusion protein Lys-Li5-MSI was selected for further modifications aimed at extending its half-life. A cysteine residue was introduced into Lys-Li5-MSI through mutation (Lys-Li5-MSIV12C), followed by conjugation with a C16 fatty acid chain via a protonation substitution reaction(V12C-C16). The pharmacokinetic profile of V12C-C16 exhibited a more favorable characteristic in comparison to Lys-Li5-MSI, thereby resulting in enhanced therapeutic efficacy against lethal A. baumannii infection in mice. The study provides valuable insights for the development of novel endolysin therapeutics and proposes an alternative therapeutic strategy for combating A. baumannii infections. [ABSTRACT FROM AUTHOR]

Background Colistin-resistant Acinetobacter baumannii isolates are extremely important pathogens for hospital-acquired infections. Objective To investigate the effectiveness of the resazurin microplate assay (REMA) for the rapid determination of colistin resistance. Methods Susceptibility for colistin was investigated in vitro by the broth microdilution method (BMD) and the resazurin microplate assay (REMA) on 106 carbapenem-resistant Acinetobacter baumannii isolates. Results The results of both test methods were compared, and the categorical agreement between them was found to be 100%. No minor, major, or very major discrepancy was observed between the 2 methods. Conclusions The most important advantages of REMA are that the results are obtained within 6 hours compared to the reference method, that it is easy to evaluate because it is colorimetric, and that the susceptibility result can be reported to the clinician on the same day as bacterial identification. [ABSTRACT FROM AUTHOR]

Interactions between host and bacterial cells are integral to human physiology. The complexity of host–microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high‐resolution approaches to capture their full complexity. The latest breakthroughs in single‐cell RNA sequencing (scRNA‐seq) have opened up a new era of studies in host–pathogen interactions. Here, we first report a high‐throughput cross‐species dual scRNA‐seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom‐seq). Using reference cells, scRandom‐seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom‐seq witnessed polarization of THP‐1 derived‐macrophages and the intracellular A.b‐induced ferroptosis‐stress in host cells. The inhibition of ferroptosis by Ferrostatin‐1 (Fer‐1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom‐seq provides a high‐throughput cross‐species dual single‐cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host–microbe interactions in infection systems and tumor micro‐environments. [ABSTRACT FROM AUTHOR]

Interactions between host and bacterial cells are integral to human physiology. The complexity of host–microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high‐resolution approaches to capture their full complexity. The latest breakthroughs in single‐cell RNA sequencing (scRNA‐seq) have opened up a new era of studies in host–pathogen interactions. Here, we first report a high‐throughput cross‐species dual scRNA‐seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom‐seq). Using reference cells, scRandom‐seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom‐seq witnessed polarization of THP‐1 derived‐macrophages and the intracellular A.b‐induced ferroptosis‐stress in host cells. The inhibition of ferroptosis by Ferrostatin‐1 (Fer‐1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom‐seq provides a high‐throughput cross‐species dual single‐cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host–microbe interactions in infection systems and tumor micro‐environments. [ABSTRACT FROM AUTHOR]

Background: This study addresses the urgent need for infection control agents driven by the rise of drug-resistant pathogens such as Acinetobacter baumannii. Our primary aim was to develop and assess a novel endolysin, Tha-PA90, designed to combat these challenges. Methods: Tha-PA90 incorporates an antimicrobial peptide (AMP) called thanatin at its N-terminus, enhancing bacterial outer membrane permeability and reducing host immune responses. PA90 was selected as the endolysin component. The antibacterial activity of the purified Tha-PA90 was evaluated using an in vitro colony-forming unit (CFU) reduction assay and a membrane permeability test. A549 cells were utilized to measure the penetration into the cytosol and the cytotoxicity of Tha-PA90. Finally, infection control was monitored in A. baumannii infected mice following the intraperitoneal administration of Tha-PA90. Results: Tha-PA90 demonstrated remarkable in vitro efficacy, completely eradicating A. baumannii strains, even drug-resistant variants, at a low concentration of 0.5 μM. Notably, it outperformed thanatin, achieving only a < 3-log reduction at 4 μM. Tha-PA90 exhibited 2–3 times higher membrane permeability than a PA90 and thanatin mixture or PA90 alone. Tha-PA90 was found within A549 cells' cytosol with no discernible cytotoxic effects. Furthermore, Tha-PA90 administration extended the lifespan of A. baumannii-infected mice, reducing bacterial loads in major organs by up to 3 logs. Additionally, it decreased proinflammatory cytokine levels (TNF-α and IL-6), reducing the risk of sepsis from rapid bacterial lysis. Our findings indicate that Tha-PA90 is a promising solution for combating drug-resistant A. baumannii. Its enhanced efficacy, low cytotoxicity, and reduction of proinflammatory responses render it a potential candidate for infection control. Conclusions: This study underscores the significance of engineered endolysins in addressing the pressing challenge of drug-resistant pathogens and offers insights into improved infection management strategies. [ABSTRACT FROM AUTHOR]

This review explores the evolution of the concept of Healthcare-Associated Pneumonia (HCAP) in light of the 2016 guidelines from the Infectious Diseases Society of America (IDSA). These updated guidelines prioritize patient-specific risk factors over healthcare system interactions in pneumonia classification. Recent research has revealed that the risk of contracting Multidrug-Resistant (MDR) pathogens is more closely linked to individual patient risk factors than to healthcare system interactions. Consequently, administering empiric antibiotic therapy targeting MDR bacteria for patients meeting HCAP criteria is discouraged unless specific risk factors for MDR infections are identifiable. Hospital-Acquired Pneumonia (HAP) is a significant challenge, particularly in intensive care units, leading to elevated hospitalization costs and extended inpatient care. The review also delves into the emergence and global prevalence of Carbapenem-Resistant Acinetobacter baumannii (CRAB) infections, known for their high mortality rates. In response to the rising threat of CRAB infections, the review introduces Sulbactam-Durlobactam (SUL-DUR) as a promising therapeutic solution. It examines the unique characteristics of Sulbactam and Durlobactam, both individually and in combination, and their potential in treating CRAB infections. Clinical trial data is presented to demonstrate the effectiveness and safety of SUL-DUR in addressing Hospital-Acquired Bacterial Pneumonia (HABP), Ventilator-Associated Bacterial Pneumonia (VABP), and bacteremia caused by the Acinetobacter baumannii-Calcoaceticus complex. The review also covers FDA-approved prescribing guidelines, dosage recommendations, adverse reactions, drug interactions, and usage in specific populations, including pregnant and lactating individuals. The management of renal and hepatic impairment and underscores the importance of monitoring for potential overdosage. While initial clinical evidence is promising, further research is essential to establish the full efficacy and safety profile of SUL-DUR. [ABSTRACT FROM AUTHOR]

Background: Presently, many laboratories are equipped with automated system for antimicrobial susceptibility testing (AST) for minimum inhibitory concentration-based reporting which enables the clinician to choose the right antimicrobial for timely treatment of sepsis. The study aimed to assess performance of direct AST from blood culture positive broth using automated AST system for accuracy and time taken to release the report. Materials and methods: The present study conducted in a 25-bedded ICU in North India for 12 months. Single morphotype of bacteria on gram stain from positively flagged blood culture bottles were included, which was directly identified (using an in-house protocol) with MALDI-TOF-MS from positive blood culture broths. DAST was carried out from 200 such blood culture broths and results were compared with reference AST (RAST) which was also done using VITEK-2 using overnight grown bacterial colonies as per standard protocol. Results: Among 60 isolates of Enterobacterales, 99% categorical agreement for both E. coli and K. pneumoniae observed by two methods were tested for AST. Among non-fermenters, Pseudomonasaeruginosa showed a categorical agreement of 99.6%, as compared with Acinetobacterspp. and exotic GNBs, which showed 95-96% agreement. A significant difference of 18-24 hours was noted in time to release the report between DAST and RAST, for GNB and GPC both. Conclusion: Direct AST from positive flagged blood culture bottles can significantly reduce the time to release the bacterial susceptibility report by up to 24 hours, at the same time maintaining the accuracy. [ABSTRACT FROM AUTHOR]

Background & Objective: Mortality of patients with ventilator-associated pneumonia (VAP) in the ICU is influenced by several risk factors, including comorbidities, SOFA scores, malnutrition, and sepsis with multi-drug resistant (MDR) pathogens. We aimed to determine the risk factors for VAP patient mortality in the ICU of a tertiary hospital in Indonesia over a period of time. Methodology: This descriptive observational study was conducted retrospectively in the ICU of Dr. Hasan Sadikin Hospital, Bandung, Indonesia, during 2021-2022. The hospital records of all patients diagnosed with VAP during this period were retrieved and the records of the deceased patients were analysed for various risk factors, which may have led to mortality. Results: The results of this study showed that 64 patients experienced VAP, with 49 (76.6%) patients expired. The VAP patients who died were mostly male (63.3%), the median age was 61 years, median BMI of 22.2 kg/m², with hospital length of stay (LOS) of 13 days, ICU LOS of 10 days, and ventilator LOS of 8 days. The majority had SOFA scores between 10-12 (46.9%), the PF ratio was 195.1 ± 77.5, albumin value was 2.11 ± 0.64. The most common comorbidity was hypertension (40.8%) with a high neutrophil-lymphocyte ratio (NLR) value (69.4%), the most common pathogen found was Acinetobacter baumannii (18.4%), and in the most of the patients experiencing MDR (53.3%), the cause of ICU admission was respiratory system disorders (40.8%). Bivariate analysis showed hospital LOS, ICU, ventilator, PF ratio, comorbidities, NLR, SOFA score, nutritional status, and MDR pathogens were associated with VAP mortality with P < 0.05. Conclusion: This study concludes that the risk factors for mortality of VAP patients in the ICU of Dr. Hasan Sadikin Hospital, Bandung in 2021-2022 are comorbidities, a high neutrophil-lymphocyte ratio, SOFA score, poor nutritional status, and sepsis with multi-drug resistant pathogens. Identifying risk factors is essential for preventing and managing VAP in the ICU to reduce mortality. Abbreviations: LOS - Length of Stay; MDR - Multi-Drug Resistant; NLR - Neutrophil-Lymphocyte Ratio; VAP - Ventilator-Associated Pneumonia. [ABSTRACT FROM AUTHOR]

To eliminate multidrug-resistant bacteria of Acinetobacter baumannii, we screened 1100 Food and Drug Administration-approved small molecule drugs and accessed the broxyquinoline (Bq) efficacy in combination with various metal ions. Antibacterial tests demonstrated that the prepared Zn(Bq)2 complex showed ultralow minimum inhibitory concentration of ~0.21 micrograms per milliliter with no resistance after 30 passages. We then constructed the nano zeolitic imidazolate framework-8 (ZIF-8) as a drug carrier of Zn(Bq)2 and also incorporated the photosensitizer chlorin e6 (Ce6) to trace and boost the antibacterial effect. To further ensure the stable and targeted delivery, we genetically engineered outer membrane vesicles (OMVs) with the ability to selectively target A. baumannii. By coating the ZnBq/Ce6@ZIF-8 core with these OMV, the resulted drug (ZnBq/Ce6@ZIF-8@ OMV) exhibited exceptional killing efficacy (>99.9999999%) of A. baumannii. In addition, in vitro and in vivo tests were also respectively carried out to inspect the remarkable efficacy of this previously unknown nanodrug in eradicating A. baumannii infections, including biofilms and meningitis. [ABSTRACT FROM AUTHOR]

Background and Aim: Acinetobacter baumannii (A. baumannii) is an important bacterium that can cause multidrug-resistant nosocomial infections in the patients who are admitted to different hospital wards. Various factors play role in the resistance of this bacterium to antibiotics, one of the most important of which is the presence of drug efflux pumps. This study aimed to investigate the presence of the AdeABC efflux system and its role in drug resistance by inactivating them. Materials and Methods: Clinical samples were collected from three hospitals in Tehran, Iran for one year. The initial diagnosis and identification of A. baumannii was done by culture and biochemical methods. Finally, the identified prototypes were confirmed by molecular method. To investigate the role of antibiotic efflux pump in the drug resistance, minimum inhibitory concentration (MIC) for ciprofloxacin in the presence and absence of an efflux pump inhibitor, carbonyl cyanide 3- chlorophenylhydrazone (CCCP), was determined by microdilution method. Additionally, the presence of adeB, adeR, and adeS genes related to the AdeABC depletion system was investigated by PCR. Results: The results showed that more than 98% of the isolated bacteria had adeB, adeR, and adeS genes in the AdeABC depletion system. Approximately, 47.18% of these bacteria displayed a fourfold reduction in ciprofloxacin MIC levels in the presence of CCCP. Conclusion: Administration of a suitable antibiotic along with a safe efflux pump inhibitor for the treatment of A. baumannii infections can help to reduce the material and spiritual damages caused by the resistant bacteria. [ABSTRACT FROM AUTHOR]

Acinetobacter is an important nosocomial pathogen causing health care associated infections. It is highly antibiotic resistant gram-negative bacilli. The study was done to determine the prevalence of Acinetobacter species isolated from various clinical samples with their antibiotic susceptibility pattern. To determine the antimicrobial susceptibility pattern of the isolated Acinetobacter species and also the multidrug resistant mechanisms by phenotypic characterization. The retrospective study was carried out in patients diagnosed with Acinetobacter infection in the Microbiology Department, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth, Deemed To Be University, Karad, a tertiary care hospital, including the clinical departments, during the period of two years from November 2020 till November 2022. Organism identification, biochemical test, antibiotic resistance pattern and phenotypic tests such as ESBL, MBL and Carbapenemase production were performed as per the Clinical and Laboratory Standards Institute (CLSI). The Modified Hodge test (MHT) was performed for Carbapenemase production detection in Acinetobacter species. A total of 150 Acinetobacter species were isolated from clinical samples. Acinetobacter baumannii was the most prevalent species 138 (92%), followed by Acinetobacter lwoffii 10 (7%) and Acinetobacter hemolyticus 2 (1%). The isolates showed highest resistance to Ampicillin 130 (87%) and sensitive to Colistin 113 (75.3%). Most of the isolates of of Acinetobacter baumannii showed maximum ESBL 21(14%) and MBL 75 (93%) production. Modified Hodge test showed positive results in Acinetobacter baumannii, only 11 (7%). The study showed that Acinetobacter baumannii was the most prevalent species showing drug resistance by phenotypic detection methods. At present Acinetobacter is a frequent pathogen in hospital acquired infections in critically ill patients admitted to ICU. The isolates of Acinetobacter species in our study showed resistant to most commonly used antibiotics. The study showed that ESBL production in Acinetobacter was 22 (15%) and MBL 80 (53%). Most Acinetobacter isolates were Multi Drug Resistant (MDR). MDR Acinetobacter is widely increasing due to inappropriate use of antibiotics in healthcare hospital. In our study, detection of carbapenemase by Modified Hodge test was positive in 11 (7%) isolates. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Impaired mucociliary clearance due to altered respiratory physiology in COPD presents an exceptional opportunity for bacterial proliferation. Sampling the respiratory tract using sputum or Bronchoalveolar Lavage (BAL) can be labourious and inconvenient, particularly in chronically debilitated patients. Saliva offers an interesting and non invasive method for assessing COPD patients and preventing exacerbations. Aim: To use saliva to analyse the association between the frequency of positive Potentially Pathological Bacterial Isolates (PPBI) and COPD exacerbations in relation to the frequency of exacerbations and the severity of the disease. Materials and Methods: This cross-sectional study was conducted over a period of one year (July 2022 to June 2023) among COPD patients attending the outpatient department at the Department of Respiratory Medicine, GMERS Medical College, Gotri, Vadodara, Gujarat, India. A total of 60 patients with COPD, diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021 guidelines, were included. The patients were categorised based on the severity of airflow limitation, GOLD "ABCD" assessment tool, and number of exacerbations. Salivary samples were collected and subjected to microbiological analysis using laboratory conventional culture techniques. Analysis of Variance (ANOVA) and t-tests were applied. Results: The mean age was 64±5.1 years. S. pneumoniae and H. influenza were common bacterial findings in all stages of COPD, while E. coli and A. baumannii were isolated in GOLD Group D patients. Disease severity also showed a significant association with oral bacterial composition (p=0.010) and the frequency of exacerbations (p=0.03). Conclusion: The current study demonstrates an association between oral bacteria and COPD, especially in patients with severe symptoms (GOLD Group D). Additionally, patients with repeated exacerbations exhibited a different oral bacterial composition, thus supporting the use of saliva as a non invasive specimen for assessing heterogeneous diseases like COPD and designing an empiric antibiotic regimen for those PPBI. [ABSTRACT FROM AUTHOR]

Purpose To characterize the susceptibilities of positive bacterial cultures and the appropriateness of empiric antimicrobial regimens for patients admitted from post–acute care facilities (PACFs). Methods This was a retrospective quality improvement study. The study included patients admitted from a PACF to one of 2 tertiary care teaching hospitals within the University of Pennsylvania Health System, located in Philadelphia, PA, from August 2020 to December 2021. Patients were included if they had at least one positive culture within 72 hours of admission. Results A total of 167 patients and 230 isolates from the study period were evaluated. The majority of positive cultures were from a urinary source (114 of 230, 49.6%). Nineteen patients (11.4%) had a history of multidrug-resistant organisms. The most common empiric antibiotics used were vancomycin (61.7%) and cefepime (59.3%). Sixty-one patients (36.5%) received inappropriate empiric therapy based on the culture results. When comparing our hospitals' general antibiogram to that of only PACF patients, Escherichia coli and Klebsiella pneumoniae had at least a 20% difference in susceptibility to levofloxacin, ceftriaxone, and cefepime. Extended-spectrum β-lactamase resistance was also higher in the PACF cohort (odds ratio, 2.09; 95% confidence interval, 1.4-3.1). Conclusion Clinically significant differences in antimicrobial susceptibility were found among patients admitted from PACFs compared to our health system's general antibiogram. The increased resistance rates identified in this study support the need for hospitals to evaluate this at-risk patient population, which may drive changes to empiric antibiotic prescribing practices. [ABSTRACT FROM AUTHOR]

(+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2–10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated. [ABSTRACT FROM AUTHOR]

The rapidly increasing threat of multi-drug-resistant Acinetobacter baumannii infections globally, encompassing a range of clinical manifestations from skin and soft tissue infections to life-threatening conditions like meningitis and pneumonia, underscores an urgent need for novel therapeutic strategies. These infections, prevalent in both hospital and community settings, present a formidable challenge to the healthcare system due to the bacterium's widespread nature and dwindling effective treatment options. Against this backdrop, the exploration of bacterial short-chain dehydrogenase reductases (SDRs) emerges as a promising avenue. These enzymes play pivotal roles in various critical bacterial processes, including fatty acid synthesis, homeostasis, metabolism, and contributing to drug resistance mechanisms. In this study, we present the first examination of the X-ray crystallographic structure of an uncharacterized SDR enzyme from A. baumannii. The tertiary structure of this SDR is distinguished by a central parallel β-sheet, consisting of seven strands, which is flanked by eight α-helices. This configuration exhibits structural parallels with other enzymes in the SDR family, underscoring a conserved architectural theme within this enzyme class. Despite the current ambiguity regarding the enzyme's natural substrate, the importance of many SDR enzymes as targets in anti-bacterial agent design is well-established. Therefore, the detailed structural insights provided in this study open new pathways for the in-silico design of therapeutic agents. By offering a structural blueprint, our findings may provide a platform for future research aimed at developing targeted treatments against this and other multi-drug-resistant infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nosocomial infections represent one of the biggest health problems nowadays. Acinetobacter baumannii is known as an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived infection. It is known that in recent years, more and more bacteria have become multidrug-resistant (MDR) and, for this reason, the development of new drugs is a priority. However, these products must not affect the human body, and therefore, cytotoxicity studies are mandatory. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acinetobacter baumannii. The cytotoxicity of these compounds was investigated on the HEp-2 cell line by MTT cell viability assay. Thereafter, we studied the morphological alterations caused by the action of one of the active peptides on the bacterial membrane using atomic force microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibited antibacterial activity with Minimum Inhibitory Concentrations (MICs) ranging from 3.125 to 12.5 μg/mL and Minimum Bactericidal Concentrations (MBCs) ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of the treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that dermaseptins might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter baumannii infections. [ABSTRACT FROM AUTHOR]

Infections caused by Acinetobacter baumannii, a Gram‐negative opportunistic pathogen, are difficult to eradicate due to the bacterium's propensity to quickly gain antibiotic resistances and form biofilms, a protective bacterial multicellular community. The A. baumannii DNA damage response (DDR) mediates the antibiotic resistance acquisition and regulates RecA in an atypical fashion; both RecALow and RecAHigh cell types are formed in response to DNA damage. The findings of this study demonstrate that the levels of RecA can influence formation and dispersal of biofilms. RecA loss results in surface attachment and prominent biofilms, while elevated RecA leads to diminished attachment and dispersal. These findings suggest that the challenge to treat A. baumannii infections may be explained by the induction of the DDR, common during infection, as well as the delicate balance between maintaining biofilms in low RecA cells and promoting mutagenesis and dispersal in high RecA cells. This study underscores the importance of understanding the fundamental biology of bacteria to develop more effective treatments for infections. [ABSTRACT FROM AUTHOR]

Introduction: Acinetobacter species are aerobic gram-negative bacteria that are ubiquitous in nature. Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. We aimed this study to evaluate resistance pattern of a threatening pathogen i.e., Acinetobacter baumannii. Materials and method: The present study was conducted in Microbiology Department of SBKSMIRC, Dhiraj Hospital, Waghodia, Gujarat during May 2022 to December 2022. This study included all Acinetobacter baumannii isolated from all ages and microbiological specimens which were referred to Central Microbiology Laboratory of Dhiraj Hospital. The Non-Lactose fermenting, oxidase negative organisms are kept in VITEK 2 automated system for identification and sensitivity. All isolates identified as Acinetobacter baumannii were included in the study. Results: This study included a total of 52 isolates of A.baumannii. Out of which 33% were respiratory samples (sputum, Endo-tracheal secretions), 33% were pus samples, 11% were urine samples and 23% were included in other (blood, CSF, Body fluids). The most resistant drug was ceftriaxone (88.46%). Tigecycline was found to be 100% sensitive. Conclusion: This study concludes that Tigecycline is the only drug which is most sensitive for A. baumannii and other higher drugs such as Polymixin B, Colistin etc. shows less resistance. Acinetobacter infection would remain a therapeutic challenge in our hospital and health care settings due to the increasing rate of Acinetobacter species with traits of MDR and resistance to high potent antimicrobial agents. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the epidemiology of Acinetobacter species in the last 5 years, the clinical diseases caused by the pathogen, the possible risk factors for infection, and the resistance pattern of the microorganism in our quaternary-care hospital. Materials and Methods: In this retrospective cohort study, 67 pediatric cases infected with Acinetobacter species in our hospital between January 2017 and December 2021 were analyzed. Demographic characteristics and clinical and laboratory findings were analyzed. Results: In pediatric patients infected with Acinetobacter spp., the median age was 36 (7-114) months, and 64.2% (n = 43) were female. Acinetobacter baumannii was grown in the cultures of 31 (46.3%) cases. When the type of infection was examined, 31 (46.3%) cases were urinary tract infections, and 29 (43.3%) cases were bloodstream infections. Extensively drug-resistant, pandrug-resistant, and multidrug-resistant A. baumannii were found in 10 (14.9%), 3 (4.5%), and 2 (3%) cases, respectively. Health-care-associated infections were found to have a significant rate of Acinetobacter resistance (P = .002). Significant antimicrobial resistance was detected in Acinetobacter-infected cases with intensive care hospitalization within the last month and carbapenem use in the previous 3 months (P < .001, both). Conclusion: It is necessary to act in accordance with the infection prevention and control program to reduce the incidence of health-care-associated infections with Acinetobacter species and to prevent infection with highly resistant strains. Due to health-care-associated infections and factors contributing to the increase in Acinetobacter resistance, we believe this study will help clinicians to be more cautious in the use of carbapenems. [ABSTRACT FROM AUTHOR]

Background: Unprecedented levels of antimicrobial resistance in bacterial isolates have prompted great concerns globally and have imposed significant life threatening risks to several different populations, especially those in intensive care units (ICUs). Among Gram-negative bacteria, Acinetobacter baumannii is notorious as a frequent opportunistic pathogen associated with critically ill patients The objective of the present study is to determine the prevalence and risk factors of Carbapenem Resistant Acinetobacter baumannii (CRAB) infections among patients admitted in ICU in a tertiary care hospital in North East India. Materials and Methods: A total of 215 Acinetobacter baumannii isolates obtained from patients admitted in ICU between 2019-2020 were included in the study, retrospectively. All the isolates were screened for carbapenem resistance by Kirby Bauer Disc Diffusion method and were further subjected for MIC (Minimum Inhibitory Concentration) testing by VITEK 2 automated system. The statistical analysis was done using MedCalc for Windows version 19.1 (Ostend, Belgium). Significance of statistical association had been calculated from standard probability (p- value) using Chi-Square test. Results: Carbapenem resistance was observed in 149 (69%) out of 215 Acinetobacter baumannii isolates. Majority of the resistant isolates had MIC values of ≥16µg/ml and ≤64µg/ml (85.2% for Imipenem and 87.3% for Meropenem). Most common risk factors of infection were mechanical ventilation (56.4%), prolonged ICU stay (44.5%) and multidrug resistance (43.6%). The isolates were highly resistant to Cephalosporins including Ceftazidime (91.9%) and Ceftriaxone (81.2%) whereas they showed maximum sensitivity towards Levofloxacin (54.4%), Aminoglycosides including Gentamicin (53.7%) and Amikacin (53%). Conclusion: This study highlights an increasing trend of carbapenem resistance amongst Acinetobacter baumannii isolates in North East India. [ABSTRACT FROM AUTHOR]

Purpose Sulbactam/durlobactam is a combination antibiotic designed to target Acinetobacter baumannii , including carbapenem-resistant and multidrug-resistant strains. The objective of this study was to determine the physical compatibility of sulbactam/durlobactam solution during simulated Y-site administration with 95 intravenous (IV) drugs. Methods Vials of sulbactam/durlobactam solution were diluted in 0.9% sodium chloride injection to a volume of 100 mL (the final concentration of both drugs was 15 mg/mL). All other IV drugs were reconstituted according to the manufacturer's recommendations and diluted with 0.9% sodium chloride injection to the upper range of concentrations used clinically or tested undiluted as intended for administration. Y-site conditions were simulated by mixing 5 mL of sulbactam/durlobactam with 5 mL of the tested drug solutions in a 1:1 ratio. Solutions were inspected for physical characteristics (clarity, color, and Tyndall effect), turbidity, and pH changes before admixture, immediately post admixture, and over 4 hours. Incompatibility was defined as any observed precipitation, significant color change, positive Tyndall test, or turbidity change of ≥0.5 nephelometric turbidity unit during the observation period. Results Sulbactam/durlobactam was physically compatible with 38 out of 42 antimicrobials tested (90.5%) and compatible overall with 86 of 95 drugs tested (90.5%). Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, ciprofloxacin, daptomycin, levofloxacin, phenytoin sodium, vecuronium, and propofol. Conclusion The Y-site compatibility of sulbactam/durlobactam with 95 IV drugs was described. These compatibility data will assist pharmacists and nurses to safely coordinate administration of IV medications with sulbactam/durlobactam. [ABSTRACT FROM AUTHOR]

Background: Accurately distinguishing between pulmonary infection and colonization in patients with Acinetobacter baumannii is of utmost importance to optimize treatment and prevent antibiotic abuse or inadequate therapy. An efficient automated sorting tool could prompt individualized interventions and enhance overall patient outcomes. This study aims to develop a robust machine learning classification model using a combination of time-series chest radiographs and laboratory data to accurately classify pulmonary status caused by Acinetobacter baumannii. Methods: We proposed nested logistic regression models based on different time-series data to automatically classify the pulmonary status of patients with Acinetobacter baumannii. Advanced features were extracted from the time-series data of hospitalized patients, encompassing dynamic pneumonia indicators observed on chest radiographs and laboratory indicator values recorded at three specific time points. Results: Data of 152 patients with Acinetobacter baumannii cultured from sputum or alveolar lavage fluid were retrospectively analyzed. Our model with multiple time-series data demonstrated a higher performance of AUC (0.850, with a 95% confidence interval of [0.638–0.873]), an accuracy of 0.761, a sensitivity of 0.833. The model, which only incorporated a single time point feature, achieved an AUC of 0.741. The influential model variables included difference in the chest radiograph pneumonia score. Conclusion: Dynamic assessment of time-series chest radiographs and laboratory data using machine learning allowed for accurate classification of colonization and infection with Acinetobacter baumannii. This demonstrates the potential to help clinicians provide individualized treatment through early detection. [ABSTRACT FROM AUTHOR]

Background: Colistin is an antibiotic used as a last-resort to treat multidrug-resistant Gram-negative bacterial infections. Colistin had been used for a long time in veterinary medicine for disease control and as a growth promoter in food-producing animals. This excessive use of colistin in food animals causes an increase in colistin resistance. This study aimed to determine molecular characteristics of colistin-resistant Escherichia coli in broiler chicken and chicken farm environments. Results: Four hundred fifty-three cloacal and farm environment samples were collected from six different commercial chicken farms in Kelantan, Malaysia. E. coli was isolated using standard bacteriological methods, and the isolates were tested for antimicrobial susceptibility using disc diffusion and colistin minimum inhibitory concentration (MIC) by broth microdilution. Multiplex PCR was used to detect mcr genes, and DNA sequencing was used to confirm the resistance genes. Virulence gene detection, phylogroup, and multilocus sequence typing (MLST) were done to further characterize the E. coli isolates. Out of the 425 (94%; 425/453) E. coli isolated from the chicken and farm environment samples, 10.8% (48/425) isolates were carrying one or more colistin-resistance encoding genes. Of the 48 colistin-resistant isolates, 54.2% (26/48) of the mcr positive isolates were genotypically and phenotypically resistant to colistin with MIC of colistin ≥ 4 μg/ml. The most prominent mcr gene detected was mcr-1 (47.9%; 23/48), followed by mcr-8 (18.8%; 9/48), mcr-7 (14.5%; 7/48), mcr-6 (12.5%; 6/48), mcr-4 (2.1%; 1/48), mcr-5 (2.1%; 1/48), and mcr-9 (2.1%; 1/48) genes. One E. coli isolate originating from the fecal sample was found to harbor both mcr-4 and mcr-6 genes and another isolate from the drinking water sample was carrying mcr-1 and mcr-8 genes. The majority of the mcr positive isolates were categorized under phylogroup A followed by phylogroup B1. The most prevalent sequence typing (ST) was ST1771 (n = 4) followed by ST206 (n = 3). 100% of the mcr positive E. coli isolates were multidrug resistant. The most frequently detected virulence genes among mcr positive E. coli isolates were ast (38%; 18/48) followed by iss (23%; 11/48). This is the first research to report the prevalence of mcr-4, mcr-5, mcr-6, mcr-7, and mcr-8 genes in E. coli from broiler chickens and farm environments in Malaysia. Conclusion: Our findings suggest that broiler chickens and broiler farm environments could be reservoirs of colistin-resistant E. coli, posing a risk to public health and food safety. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a Gram-negative multidrug-resistant bacterial pathogen primarily associated with nosocomial infections resulting in increased morbidity and mortality in adults and infants, especially in sub-Saharan Africa where the clinical burden is high. New therapeutics are needed to treat multidrug-resistant Acinetobacter baumannii infections and reduce transmission. The study used computer-integrated drug discovery approaches including pharmacophore modelling, molecular docking, and molecular dynamics simulation to screen potential inhibitors against the enoyl-acyl carrier protein reductase—FabI protein of Acinetobacter baumannii. The top three potential inhibitors: 21272541 > 89795992 > 89792657 showed favourable binding free energies including coulombic energy, van der Waals energy, and polar and non-polar energies. Furthermore, all three complexes were extremely stable and compact with reduced fluctuations during the simulations period. Inhibitor 21272541 exhibited the highest binding affinity against the Acinetobacter baumannii FabI protein. This is similar to our recent report, which also identified 21272541 as the lead inhibitor against Klebsiella pneumoniae infections. Future clinical studies evaluating drug effectiveness should prioritise inhibitor 21272541 which could be effective in treating infections caused by Gram-negative organisms. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a Gram-negative multidrug-resistant bacterial pathogen primarily associated with nosocomial infections resulting in increased morbidity and mortality in adults and infants, especially in sub-Saharan Africa where the clinical burden is high. New therapeutics are needed to treat multidrug-resistant Acinetobacter baumannii infections and reduce transmission. The study used computer-integrated drug discovery approaches including pharmacophore modelling, molecular docking, and molecular dynamics simulation to screen potential inhibitors against the enoyl-acyl carrier protein reductase—FabI protein of Acinetobacter baumannii. The top three potential inhibitors: 21272541 > 89795992 > 89792657 showed favourable binding free energies including coulombic energy, van der Waals energy, and polar and non-polar energies. Furthermore, all three complexes were extremely stable and compact with reduced fluctuations during the simulations period. Inhibitor 21272541 exhibited the highest binding affinity against the Acinetobacter baumannii FabI protein. This is similar to our recent report, which also identified 21272541 as the lead inhibitor against Klebsiella pneumoniae infections. Future clinical studies evaluating drug effectiveness should prioritise inhibitor 21272541 which could be effective in treating infections caused by Gram-negative organisms. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to expand real-life data on cefiderocol efficacy to treat multidrug-resistant Acinetobacter baumannii infections. Methods This was a retrospective monocentric study including patients hospitalized (>24 hours) at Policlinico Tor Vergata, Rome, Italy, between May 1, 2021, and September 1, 2022, treated with cefiderocol (>48 hours). The primary objective was early clinical improvement at 48–72 hours from cefiderocol start; secondary objectives were clinical success (composite outcome of infection resolution and 14-day survival), breakthrough infection, overall 30-day mortality, and cefiderocol-related adverse events. Results Eleven patients were enrolled; 91% males (10/11), with a median age (interquartile range [IQR]) of 69 (59–71) years, 91% had ≥1 comorbidity, and 72.7% (8/11) were hospitalized in internal medicine wards. Six patients with bloodstream infection (54.5%; 4 primary, 2 central line–associated), 2 with pneumonia (18.2%), 2 with urinary tract infections (18.2%), and 1 with intra-abdominal infection (9.1%) were treated. Four patients (36.3%) presented with septic shock at cefiderocol start. Cefiderocol was used as monotherapy in 3/11 patients (27.3%), was combined with colistin in all the other 8 cases, and was used in triple combination with tigecycline in 2 patients. The median duration of treatment (IQR) was 12 (10–14) days. Early clinical improvement was documented in 8/11 patients (72.7%), clinical success in 8/11 patients (72.7%). Overall 30-day mortality was 27.3% (3/11), with death occurring a median (IQR) of 19 (17.5–20.5) days after the start of therapy. No cefiderocol-related adverse events were documented. Conclusions Cefiderocol seems to be a safe and effective option for multidrug-resistant Acinetobacter baumannii infections. [ABSTRACT FROM AUTHOR]

Background Sulbactam-durlobactam is a potent combination active against Acinetobacter baumannii ; however, it lacks activity against other nosocomial pathogens. Cefepime is a common first-line therapy for hospital/ventilator-associated pneumonia caused by Gram-negative pathogens including Pseudomonas aeruginosa and Enterobacterales. With increasing resistance to cefepime, and the significant proportion of polymicrobial nosocomial infections, effective therapy for infections caused by Acinetobacter baumannii , P. aeruginosa and Enterobacterales is needed. This study investigated the in vitro synergy of sulbactam-durlobactam plus cefepime against relevant pathogens. Methods Static time–kills assays were performed in duplicate against 14 cefepime-resistant isolates (A. baumannii , n  = 4; P. aeruginosa , n  = 4; Escherichia coli , n  = 3; Klebsiella pneumoniae , n  = 3). One WT K. pneumoniae isolate was included. Antibiotic concentrations simulated the free-steady state average concentration of clinically administered doses in patients. Results Sulbactam-durlobactam alone showed significant activity against A. baumannii consistent with the MIC values. Sulbactam-durlobactam plus cefepime showed synergy against one A. baumannii isolate with an elevated MIC to sulbactam-durlobactam (32 mg/L). Against all P. aeruginosa isolates, synergy was observed with sulbactam-durlobactam plus cefepime. For the Enterobacterales, one E. coli isolate demonstrated synergy while the others were indifferent due to significant kill from sulbactam-durlobactam alone. The combination of sulbactam-durlobactam plus cefepime showed synergy against one of the K. pneumoniae and additive effects against the other two K. pneumoniae tested. No antagonism was observed in any isolates including the WT strain. Conclusions Synergy and no antagonism was observed with a combination of sulbactam-durlobactam and cefepime; further in vivo pharmacokinetic/pharmacodynamics data and clinical correlation are necessary to support our findings. [ABSTRACT FROM AUTHOR]

This study aimed to characterize the molecular features and virulence profiles of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Clinical CRAB isolates were obtained from blood cultures of adult patients with CRAB bacteremia, collected between July 2015 and July 2021 at a Korean hospital. Real-time polymerase chain reaction was used to detect 13 virulence genes, genotyping was conducted via multilocus sequence typing (MLST), and a Tenebrio molitor infection model was selected for survival analysis. Herein, 170 patients, from whom CRAB isolates were collected, showed the in-hospital mortality rate of 57.6%. All 170 clinical CRAB isolates harbored blaOXA-23 and blaOXA-51. MLST genotyping identified 11 CRAB sequence types (STs), of which ST191 was predominant (25.7%). Virulence genes were distributed as follows: basD, 58.9%; espA, 15.9%; bap, 92.4%; and ompA, 77.1%. In the T. molitor model, ST195 showed a significantly higher mortality rate (73.3% vs. 66.7%, p = 0.015) than the other groups. Our findings provide insights into the microbiological features of CRAB blood isolates associated with high mortality. We suggest a potential framework for using a T. molitor infection model to characterize CRAB virulence. Further research is warranted to elucidate the mechanisms by which virulence improves clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the clinical isolates of patients infected by Stenotrophomonas maltophilia (S. maltophilia) in the intensive care unit (ICU) at King Khalid Hospital, Kingdom of Saudi Arabia (KSA), and to identify the healthcare complications, antimicrobial resistance patterns, and risk factors associated with infection for this emerging pathogen. Methodology: In this cross-sectional observational study, patients admitted in the ICU (n = 127) were analyzed, and 36 non-duplicating S. maltophilia strains were clinically isolated in King Khalid Hospital, KSA between September 2020 and April 2021. Antimicrobial susceptibility testing was performed using standard antibiotics (n = 13). Results: In this study, 36 clinical isolates of S. maltophilia were identified as true infection pathogens. The main locations of S. maltophilia infection were in the respiratory tract (13, 36.1%) followed by surgical area (10, 27.7%) and wound infection (7, 19.4%). The significant risk factors included a medical history of respiratory infection, exposure to a bomb blast, and infected from an implant (p < 0.05). Among the 36 clinical isolates, 5 strains were positive for extended spectrum beta-lactamase (ESBL). The most active antimicrobials were vancomycin (69.4% sensitivity) and trimethoprim/sulfamethoxazole (80.5% sensitivity). Conclusions: Our study concludes that S. maltophilia is an emerging nosocomial pathogen in the ICU, indicating the possibility of direct or indirect transfer from one person to another. Specific identification and active antibiotic susceptibility testing of S. maltophilia are needed for the treatment management and prevention of spread of the S. maltophilia pathogen. [ABSTRACT FROM AUTHOR]

Background and Aim: Conjunctival squamous cell carcinoma (CSCC) is the final stage of ocular surface squamous neoplasia (OSSN). The microbiome plays a critical role in eye disease and health. Changes in the eye microbiome may be involved in the development of OSSN. Materials and Methods: The sampling for this case-control study involved rolling sterile rayon-tipped swabs on the conjunctival tissue of both patients and controls. The detection of bacterial communities, including Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), Staphylococcus haemolyticus (S. haemolyticus), Corynebacterium spp., and Acinetobacter spp. The study was conducted using the TaqMan quantitative real-time polymerase chain reaction (qPCR) method, which targets the 16S rDNA gene from bacteria in various samples. Results: The results showed that the frequency of Corynebacterium spp. was the same in both the patient and control groups (77.88%). Further, it exhibited the highest copy number compared to other bacteria. In general, a significant difference was observed in the total amounts of P.aeruginosa, S. aureus, and S. haemolyticus among patients, with a P-value < 0.001, additionally, Acinetobacter spp. showed a significant difference with a P-value = 0.004. 88.9% of S. haemolyticus (P=0.002) and 83.3% of P. aeruginosa (P=0.033) were detected in the OSSN group, and no detection of these bacteria was observed in any of the control samples. Conclusion: The study found a significant difference in some bacterial strains between patients with OSSN and those without OSSN. Understanding the function and composition of the ocular surface microbiome can provide insights into ocular surface diseases. [ABSTRACT FROM AUTHOR]

Background Cefiderocol is a novel siderophore cephalosporin with promising activity against most carbapenem-resistant Gram-negative bacteria (CRGNB). However, extensive postmarketing experiences are lacking. This study aimed to analyse the early experience on cefiderocol postmarketing use at three tertiary care hospitals in Italy. Methods We retrospectively included patients with infections caused by CRGNB treated with cefiderocol at three Italian tertiary care hospitals from 1 March 2021 to 30 June 2022. A multivariate Cox model was used to identify predictors of 30 day mortality. A propensity score (PS) analysis with inverse probability weighting (IPW) was also performed to compare the treatment effect of cefiderocol monotherapy (CM) versus combination regimens (CCRs). Results The cohort included 142 patients (72% male, median age 67 years, with 89 cases of Acinetobacter baumannii infection, 22 cases of Klebsiella pneumoniae , 27 cases of Pseudomonas aeruginosa and 4 of other pathogens). The 30 day all-cause mortality was 37% (52/142). We found no association between bacterial species and mortality. In multivariate analysis, a Charlson Comorbidity Index >3 was an independent predictor of mortality (HR 5.02, 95% CI 2.37–10.66, P  < 0.001). In contrast, polymicrobial infection (HR 0.41, 95% CI 0.21–0.82, P  < 0.05) was associated with lower mortality. There was no significant difference in mortality between patients receiving CM (n  = 70) and those receiving a CCR (n  = 72) (33% versus 40%, respectively), even when adjusted for IPW-PS (HR 1.11, 95% CI 0.63–1.96, P  = 0.71). Conclusions Real-life data confirm that cefiderocol is a promising option against carbapenem-resistant Gram-negative infections, even as monotherapy. [ABSTRACT FROM AUTHOR]

Addressing the treatment and prevention of antibacterial-resistant gram-negative bacterial infections is a priority area of the Antibacterial Resistance Leadership Group (ARLG). The ARLG has conducted a series of observational studies to define the clinical and molecular global epidemiology of carbapenem-resistant and ceftriaxone-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa , and carbapenem-resistant Acinetobacter baumannii , with the goal of optimizing the design and execution of interventional studies. One ongoing ARLG study aims to better understand the impact of fluoroquinolone-resistant gram-negative gut bacteria in neutropenic patients, which threatens to undermine the effectiveness of fluoroquinolone prophylaxis in these vulnerable patients. The ARLG has conducted pharmacokinetic studies to inform the optimal dosing of antibiotics that are important in the treatment of drug-resistant gram-negative bacteria, including oral fosfomycin, intravenous minocycline, and a combination of intravenous ceftazidime-avibactam and aztreonam. In addition, randomized clinical trials have assessed the safety and efficacy of step-down oral fosfomycin for complicated urinary tract infections and single-dose intravenous phage therapy for adult patients with cystic fibrosis who are chronically colonized with P. aeruginosa in their respiratory tract. Thus, the focus of investigation in the ARLG has evolved from improving understanding of drug-resistant gram-negative bacterial infections to positively affecting clinical care for affected patients through a combination of interventional pharmacokinetic and clinical studies, a focus that will be maintained moving forward. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Acinetobacter baumannii infection is a critically prioritized pathogen by the World Health Organization and a cause for growing concern due to increased mortality among hospitalised patients. Phrenic nerve palsy is a rare complication of herpes zoster infection of the C3, C4, and C5 nerve roots. We present a case of bloodstream carbapenem-resistant A. baumannii infection in a Ghanaian patient with HIV type 1 infection and multiple risk factors, including unilateral diaphragmatic eventration with compression atelectasis likely secondary to phrenic nerve palsy due to herpes zoster infection, consequently leading to recurrent hospital and ICU admission. In this case, we emphasize the need for clinicians in LMICs to be aware of CRAB, in order to advocate for the availability of evidence-based medicines in resource-limited settings for appropriate treatment. In addition, we illustrate the importance of a high index of suspicion for infection with carbapenem-resistant organisms such as A. baumannii and highlight a rare and severe complication of herpes zoster infection in the form of phrenic nerve palsy and consequent diaphragmatic eventration. [ABSTRACT FROM AUTHOR]

Background & Objective: Acinetobacter baumannii strains harboring Meallobetalactamases (MBL) pose a significant threat in the context of nosocomial infections. The present investigation was undertaken with the objective of devising a Multiplex PCR methodology for the concurrent detection of MBL genes within A. baumannii strains prevalent in Tehran City, Iran. Methods: Between October 2020 and February 2021, 100 strains of A. baumannii were procured from burn specimens of hospitalized patients at Motahhari Hospital in Tehran. The identification of A. baumannii strains involved conventional biochemical techniques, coupled with confirmation of the presence of the bla OXA-51 gene. Antibiotic susceptibility was assessed using the Kirby--Bauer disc diffusion test. MBL-producing strains were characterized through a phenotypic approach employing the combined disk test, alongside Multiplex PCR for the simultaneous identification of bla VIM, bla IMP, bla GIM, and bla NDM genes. Statistical analyses were conducted using the chi-square test, with SPSS version 20.0 employed for data processing. Results: Among 100 strains examined, 96.1% exhibited positivity for MBL, as determined by the combined disk test. The study revealed a predominance of extensively drug-resistant (XDR) strains, with colistin demonstrating the highest level of sensitivity. The genotypic assay unveiled that Multiplex PCR identified bla VIM, bla NDM, and bla IMP in 20 strains, bla VIM and bla NDM in 30 strains, and exclusively the bla NDM gene in 45 strains. Notably, the Multiplex PCR technique exhibited the capacity to concurrently detect MBL genes (bla VIM, bla IMP, bla GIM, bla NDM) in 2 strains. Conclusion: The current investigation underscores prevalence of the bla NDM gene within clinical strains of A. baumannii. Furthermore, Multiplex PCR emerges as a robust and highly sensitive technique for rapid discernment of the MBL genes within in A. baumannii strains. [ABSTRACT FROM AUTHOR]

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

Background: In the era of rising carbapenem resistance, we aimed to investigate the change in mortality rate and positivity of carbapenemase genes in Acinetobacter baumannii. Methods: Preferred Reporting Items for Systematic Review (PRISMA) guidelines were adopted in this systematic review. Our literature search included the Cochrane Library, Pubmed, Scopus, Web of Science, Medline, Tubitak TR Dizin, and Harman databases for studies dating back from 2003 to 2023 reporting bloodstream A. baumannii infections in Türkiye. A simple linear regression model was used to determine the association between resistance, mortality, and time. Results: A total of 1717 studies were identified through a literature search, and 21 articles were selected based on the availability of the data regarding mortality and resistance rate (four articles) or the molecular epidemiology of carbapenem-resistant A. baumannii (17 articles) in Türkiye. From 2007 to 2018, the carbapenem resistance rate increased (p = 0.025). The OXA-23 and OXA-58 positivities were inversely correlated (p = 0.025). Conclusions: Despite the emergence of carbapenem resistance, mortality did not increase in parallel, which may be due to improved medical advancements or the fitness cost of bacteria upon prolonged antimicrobial exposure. Therefore, we suggest further global research with the foresight to assess clonal relatedness that might affect the carbapenem resistance rate. [ABSTRACT FROM AUTHOR]

Objective: Bacterial and fungal infections, antimicrobial resistance (AMR) results of bacterial agents, and the effect of the pandemic on AMR were evaluated in hospitalized COVID-19 patients. In addition, the detected AMR rates were compared with the AMR rates of the pre-pandemic period. Patients and Methods: The isolates grown in respiratory and blood samples of adult patients hospitalized with the diagnosis of COVID-19 between March 2020 and December 2020 were evaluated retrospectively. The same data in hospitalized patients before the pandemic, between March and December 2019, were evaluated retrospectively. Results: A total of 724 samples were included in the study. The superinfection rate was found to be 15.3%. The most frequently isolated microorganisms are; Acinetobacter baumannii (34.4%), Staphylococcus aureus (10.8%), Klebsiella pneumoniae (9.7%) and Pseudomonas aeruginosa (7.3%). The lowest resistance rates in Klebsiella pneumoniae isolates were found for aminoglycosides, in Acinetobacter baumannii isolates were found for trimethoprim-sulfamethoxazole, in Pseudomonas aeruginosa isolates were found for amikacin. When pre-pandemic and pandemic AMR rates were compared; a significant increase in amikacin resistance was detected only in Klebsiella pneumoniae isolates during the pandemic period (P:0.049). Conclusion: The data we have presented may help clinicians in the selection of antimicrobials for empirical therapy by revealing the effect of the pandemic on AMR. [ABSTRACT FROM AUTHOR]

• Biofilms and iron absorption fuel A. baumannii persistence. • Bap and BauA were administered into mice groups individually and in combination. • Mice were challenged with A. baumannii , to assess the bacterial load and tissue damage. • Bap and BauA combo enhanced immunoprotection against A. baumannii. • Histopathology demonstrated successful tissue protection with combined immunogens. The rise of multi-drug resistant Acinetobacter baumannii poses a grave threat to hospital settings, resulting in increased mortality rates and garnering global attention. The formation of biofilms facilitated by biofilm-associated protein (Bap) and the iron absorption capabilities mediated by Baumannii acinetobactin utilization A (BauA) contribute to the persistence and survival of multidrug-resistant strains. In this study, we aimed to investigate the potential of disrupting the function of BauA and Bap simultaneously as a strategy for controlling A. baumannii. Recombinant Bap and BauA were expressed, purified, and subcutaneously administered individually and in combination to BALB/c mice. Subsequently, mice were intraperitoneally challenged with A. baumannii , and the bacterial load and tissue damage in the spleen, lung, and liver were assessed. Serum samples were evaluated to determine antibody titers in surviving mice. Specific IgG antibodies were significantly increased. A combination of the antigens resulted in enhanced titer of specific IgGs in comparison to either BauA or Bap alone. The antibodies remained stable over a seven-month period. The combination of Bap and BauA exhibited superior immunoprotection against A. baumannii infection compared to individual administration, resulting in a further reduction in bacterial load in the liver, spleen, and lungs. The histopathological analysis demonstrated successful protection of the tissues against A. baumannii -induced damage upon administration of the two immunogens. The combination of Bap and BauA has the potential to target a broader range of A. baumannii strains, including those expressing either Bap or BauA, thereby increasing its efficacy against a diverse array of strains. [ABSTRACT FROM AUTHOR]

Objective: To investigate the pathogenic clinical characteristics and susceptibility factors of multi-drug resistant bacteria in ICU lower respiratory tract. A total of 216 patients with lower respiratory tract infection who were hospitalized in ICU of our hospital from January 2020 to December 2022 were selected and divided into study group (113 cases) and control group (103 cases) according to whether multiple drug resistant bacteria infection occurred. The number distribution of infection-related factors in the two groups was analyzed, and the risk factors of nosocomial infection of multi-drug resistant bacteria were analyzed by Logistic regression. The bacterial species were identified by automatic bacterial identification instrument, and the drug sensitivity test was carried out by K-B disk method. The pathogenic distribution and drug resistance of multi-drug resistant bacterial infection were analyzed. Results: (1) Compared with the control group, the distribution rate of infection-related factors was higher in the study group; (2) Duration of hospital >3 months, glucocorticoid therapy, mechanical ventilation therapy, other bacterial infections, hemoglobin <100 g/L, antibacterial drug use time >15 days, antibacterial drug types > 4, immunosuppressant were the risk factors of multiple drug-resistant bacterial infection in ICU lower respiratory tract; (3) 93 strains of bacteria were cultured in the study group, of which 52 (55.91%) were Gram-negative, 25 (26.88% ) were Gram-positive, and most of the gram-negative bacteria were Pseudomonas aeruginosa (22), A cinetobacter baumannii (13) and Klebsiella pneumoniae (12). The most gram-positive bacteria were Streptococcus pneumoniae (11 strains) and Staphylococcus aureus (11 strains). (4) Drug resistance showed that the resistance rate of Pseudomonas aeruginosa to moxifloxacin was low (15.83%), that of Klebsiella pneumoniae to imipenem was low (17.56% ), that of A cinetobacter baumannii to cefoperazone/sulbactam was low (16.37% ), and staphylococcus aureus and streptococcus pneumoniae showed no resistance to vancomycin. Conclusion: Hospital stay >3 months, glucocorticoid therapy, mechanical ventilation therapy, other bacterial infections, hemoglobin <100 g/L, antibacterial drug use >15 days, types of antibacterial drugs >4, immunosuppressants are independent risk factors for multidrug-resistant infections. In this hospital, Gram-negative bacilli were dominant in ICU lower respiratory tract infections, so drugs with low drug resistance should be selected according to the pathogenic bacteria, and effective measures should be taken according to the risk factors. [ABSTRACT FROM AUTHOR]

Background: Carbapenem resistance is perceived as a clinical challenge in the management of debilitated and immunocompromised patients who eventually will die from underlying diseases. We aimed to examine whether carbapenem resistance per se, rather than the underlying diseases, negatively affect outcomes, by comparing the excess mortality and morbidity from healthcare-associated infections (HAIs) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-susceptible A. baumannii (CSAB). Methods: This was a nationwide retrospective matched cohort study of hospitalized patients in 96 hospitals which participated in Taiwan Nosocomial Infection Surveillance (TNIS). A total of 2,213 patients with A. baumannii HAIs were individually matched to 4,426 patients without HAIs. Main outcomes were excess risks for one-year all-cause mortality and one-year new-onset chronic ventilator dependence or dialysis-dependent end-stage renal disease. Results: Excess one-year mortality was 27.2% in CRAB patients, compared with their matched uninfected inpatients, as well as 15.4% in CSAB patients (also compared with their matched uninfected inpatients), resulting in an attributable mortality of 11.8% (P <0.001) associated with carbapenem resistance. The excess risk associated with carbapenem resistance for new-onset chronic ventilator dependence was 5.2% (P <0.001). Carbapenem resistance was also associated with an extra cost of $2,511 per case of A. baumannii HAIs (P <0.001). Conclusion: Carbapenem resistance is associated with a significant disease burden in terms of excess mortality, long-term ventilator dependence, and medical cost. Further studies on effects of antimicrobial stewardship programs in decreasing this burden are warranted. [ABSTRACT FROM AUTHOR]