Carbapenem-resistant Acinetobacter Baumannii Research Articles

Dynamic analysis of the epidemiology and pathogen distribution of bronchoalveolar lavage fluid in children with severe pulmonary infection: a retrospective study

BackgroundSevere pulmonary infection is the primary cause of death in children aged < 5 years. The early identification of pathogenic bacteria and targeted anti-infective therapies can significantly improve the prognosis of children with severe infections. This study aims to provide a reference for the rational use of antibiotics at an early stage in children with severe pulmonary infections.MethodsA retrospective, single-center longitudinal study included children with severe pulmonary infections between January 2017 and December 2022 by obtaining their bacterial culture results of bronchoalveolar lavage fluid.ResultsThis study included 4080 samples. The age of onset for severe pulmonary infection increased annually. The proportion of severe pulmonary infections across the different age groups and years was statistically significant (p < 0.001). Among children with severe pulmonary infections, bacilli were the most prevalent, followed by cocci and fungi. The predominant bacilli were Acinetobacter baumannii and Klebsiella pneumoniae. The predominant cocci identified in this study were Streptococcus pneumoniae and Staphylococcus aureus. The primary fungi included Candida albicans and Aspergillus fumigatus, which showed significant differences (p < 0.05). The incidence of drug-resistant bacteria has gradually declined, with infection rates of multidrug-resistant bacteria and extended-spectrum beta-lactamases consistently decreasing annually. For carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, the infection rates peaked in 2018, with statistical significance (p < 0.001).ConclusionsSevere pulmonary infections in children are significantly associated with age and types of infectious pathogens. Gram-negative bacteria are the primary cause of severe pulmonary infections in children. Clinicians should rationally use antibiotics according to the local distribution and drug resistance of pathogens, thereby enhancing therapeutic outcomes.

Whole-genome evaluation and prophages characterization associated with genome of carbapenem-resistant Acinetobacter baumannii UOL-KIMZ-24-2.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an emerging threat to healthcare settings in many countries, principally in South Asia. The current study was aimed to identify, evaluate whole-genome and characterize the prophages in genome of CRAB strain, recovered from patients of Lahore General Hospital, Lahore. More than 200 samples were collected and identified by morphological and biochemical tests. These strains were also subjected to a comprehensive antimicrobial susceptibility evaluation using Kirby-Bauer method and further confirmed as CRAB strains by exploring blaOXA-51. In addition, the whole-genome evaluation of a Acinetobacter baumannii UOL-KIMZ-24-2 was carried out using various Bioinformatics tools. A total of 150 strains of A. baumannii were recovered and identified in the current study. Among them, 49% strains were found resistant to carbapenem. The blaOXA-51 was found prevalent in the genome of A. baumannii recovered from medical ICU (38%). In addition, the UOL-KIMZ-24-2 genome analysis based on multilocus sequence typing (MLST) highlighted that UOL-KIMZ-24-2 belonged to ST2 (Pasteur scheme) sequence type. A total of 29 antimicrobial resistance (AMR) genes were present, importantly, blaOXA-66, blaOXA-23 and blaOXA-25. The mobile genetic elements (MGEs) were identified as transposases and belonged to four classes e.g. IS15d1, ISAba24, ISEc29, and ISEc35. A total of 14 virulence factors encoded by 58 different genes were detected in UOL-KIMZ-24-2. In addition, the phage sequences were identified in genome of UOL-KIMZ-24-2, divided into 3 regions. In conclusion, UOL-KIMZ-24-2 contained a mixture of AMR genes, MGEs. prophages sequences and virulence genes.

Suggested Dosing of Select Beta-lactam Agents for the Treatment of Antimicrobial-Resistant Gram-Negative Infections in Children.

The Infectious Diseases Society of America (IDSA) publishes annual guidance on the treatment of antimicrobial-resistant (AMR) gram-negative infections. Within the AMR guidance, suggested dosages of antibiotics for adults infected with AMR pathogens are provided. This document serves as a companion document to the IDSA guidance to assist pediatric specialists with dosing β-lactam agents for the treatment of AMR infections in children. A panel of 13 pediatric infectious diseases specialists, including 11 pharmacists and two physicians, reviewed existing pharmacokinetic/pharmacodynamic, animal, and clinical data for newer β-lactam agents that are available in the United States and suggested for the treatment of AMR infections (i.e., cefiderocol, ceftazidime-avibactam, ceftazidime-avibactam & aztreonam, ceftolozane-tazobactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam, sulbactam-durlobactam). Suggested dosing for ampicillin-sulbactam is also provided given complexities in appropriate dosing for carbapenem-resistant Acinetobacter baumannii infections. Consensus-based suggested dosing for β-lactam agents used to treat AMR infections in neonates, infants, children, and adolescents and relevant supporting evidence are provided. Content is up to date as of December 1st, 2024. Gaps and limitations to existing data are discussed. Optimizing antibiotic dosing is critical to improving the outcomes of children with AMR infections.

Essential Oils as Antimicrobials against Acinetobacter baumannii: Experimental and Literature Data to Definite Predictive Quantitative Composition-Activity Relationship Models Using Machine Learning Algorithms.

Essential oils (EOs) exhibit a broad spectrum of biological activities; however, their clinical application is hindered by challenges, such as variability in chemical composition and chemical/physical instability. A critical limitation is the lack of chemical consistency across EO samples, which impedes standardization. Despite this, evidence suggests that EOs with differing chemical profiles often display similar (micro)biological activities, raising the possibility of standardizing EOs based on their biological effects rather than their chemical composition. This study explored the relationship between EO chemical composition and antibacterial activity against carbapenem-resistant Acinetobacter baumannii. A dataset comprising 82 EOs with known minimal inhibitory concentration values was compiled using both experimental results and literature data sourced from the AI4EssOil database (https://www.ai4essoil.com). Machine learning classification algorithms including Support Vector Machines, Random Forest, Gradient Boosting, Decision Trees, and K-Nearest Neighbors were employed to generate quantitative composition-activity relationship models. Model performance was assessed using internal and external prediction accuracy metrics with the Matthews correlation coefficient as the primary evaluation metrics. Features importance analysis, based on the Skater methodology, identified key chemical components influencing EO activity. The single chemical components limonene, eucalyptol, alpha-pinene, linalool, beta-caryophyllene, nerol, beta-pinene, neral, and carvacrol were highlighted as critical to biological efficacy. The predictive capacity of the ML models was validated against a test set of freshly extracted and chemically characterized EOs. The models demonstrated a 91% prediction accuracy for new EO samples, and a strong correlation was observed between predicted features importance and experimental inhibitory values for six selected pure compounds (limonene, eucalyptol, alpha-pinene, linalool, carvacrol, and thymol). Additionally, the machine learning approach was extended to cytotoxicity data from 3T3-Swiss fibroblasts for 61 EOs. The analysis revealed the potential to design EOs with both high antibacterial activity and low cytotoxicity through blending or selective enrichment with identified key components. These findings pave the way for biologically standardized EOs, enabling their rational design and optimization for clinical applications.

Multidrug-resistant Gram-negative bacterial infections.

Multidrug-resistant Gram-negative bacterial infections cause significant morbidity and mortality globally. These pathogens easily acquire antimicrobial resistance (AMR), further highlighting their clinical significance. Third-generation cephalosporin-resistant and carbapenem-resistant Enterobacterales (eg, Escherichia coli and Klebsiella spp), multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii are the most problematic and have been identified as priority pathogens. In response, several new diagnostic technologies aimed at rapidly detecting AMR have been developed, including biochemical, molecular, genomic, and proteomic techniques. The last decade has also seen the licensing of multiple antibiotics that have changed the treatment landscape for these challenging infections.

Understanding the clinical and molecular epidemiological characteristics of carbapenem-resistant Acinetobacter baumannii infections within intensive care units of three teaching hospitals

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) is recognized as a common clinical conditional pathogen with blaOXA−23 gene-mediated multidrug-resistance that is a significant threat to public health safety. Timely and effective infection control measures are needed to prevent their spread.MethodsWe conducted a retrospective study of CRAB patients at three teaching hospitals from 2019 to 2022. We identified bacterial isolates, collected clinical data, and performed antimicrobial susceptibility testing. Genome characteristics of isolates were investigated by whole genome sequencing. Multilocus sequence typing and phylogenetic trees were used to assess the genetic similarity of isolates. Acquired antimicrobial resistance genes and virulence factors carried in the isolated group genome were analyzed by ResFinder, PubMLST and VFDB. Sequence alignment was used to analyze genetic environment around blaOXA−23. Phylogenetic tree was constructed to analyze the genetic relationship of isolates.ResultsA total of 92 non-repetitive CRAB isolates were collected, with sputum samples accounting for the majority (94.57%, n = 87) of samples. These were distributed into ST2, with ST2 identified to have the highest prevalence of infection, accounting for 99.99% (n = 91) of all isolates. The major resistance genes identified were blaOXA−23, blaOXA−66, blaOXA−51, and blaADC. Also, 92 CRAB strains showed high levels of resistance to common clinical antibiotics, but not minocycline. Meanwhile, most of the isolates carried virulence genes such as various ompA, csuA, csuB, csuC, csuD, abaI, abaR, lpxC, lpxA, and bmfRS. Single nucleotide polymorphism (SNP) analyses further indicated that the bacterial genome was progressively polymorphic with time. We analyzed the environment of the blaOXA−23 gene and found that CRAB accumulated in the context of prominent environmental antibiotic exposure and had longer survival times in the antibiotic environment, resulting in the tendency of bacteria to develop greater antibiotic resistance.ConclusionsWe find that CRAB is prevalent within the ICU and is progressively resistant to antibiotics over time. Enhanced clinical understanding and timely management of CRAB infections will be crucial to minimize or even eliminate the spread of CRAB within the ICU setting.

Comparative study of phenotypic and genotypic expression of virulence factors in colonizing and pathogenic carbapenem resistant Acinetobacter baumannii (CRAB)

Carbapenem resistant Acinetobacter baumannii has evolved as the most troublesome microorganism with multiple virulence factors. Biofilm formation, porins, micronutrient capturing mechanism and quorum sensing, provide protection against desiccation, host-pathogen killing and enhance its persistence. The conservation of these factors between colonizing and pathogenic carbapenem resistant A. baumannii has been barely investigated. We studied biofilm formation, desiccation survival, motility and hemolysis in pathogenic carbapenem resistant A. baumannii and colonizer carbapenem resistant A. baumannii from the hospital environment. The virulent genes pgaA, csuE, bap, ompA, abaI, pilA and bauA were detected by simplex-PCR and Quantitative Real-Time PCR was done for expressional studies. In-vivo survival percentage was studied by Galleria mellonella (wax moth) killing assay. Phenotypic characterization revealed that the biofilm formation and desiccation survival proportion was significantly higher in colonizer carbapenem resistant A. baumannii (p < 0.05). Twitching motility was found comparable (mean 0.5 to 1.5 cm). Surface associated motility varied widely. None showed hemolysis. The csuE, bap, ompA, abaI, pilA and bauA genes were detected in almost all the pathogenic and colonizer carbapenem resistant A. baumannii isolates while none harboured pgaA gene. The expression of bap, ompA and bauA gene was found significantly higher in pathogenic carbapenem resistant A. baumannii while expression of csuE and abaI gene was comparable in both. Overexpression of pilA gene was seen in those with higher surface associated motility. Pathogenic carbapenem resistant A. baumannii showed significantly higher pathogenicity in-vivo, as 100% of larvae died on 4th day post-infection. In conclusion high level expression of outer membrane proteins (ompA) and siderophores is significantly associated with the pathogenicity in carbapenem resistant A. baumannii isolated from infections, which can be a differentiating point from the colonizers.Clinical TrialNot Applicable

Impact of Multidrug-Resistant Bacteria in a Cohort of COVID-19 Critically Ill Patients: Data from a Prospective Observational Study Conducted in a High-Antimicrobial-Resistance-Prevalence Center.

Background: Bacterial superinfections are common complications during viral infections, but the impact of multidrug-resistant (MDR) pathogens in critically ill patients affected by coronavirus disease 2019 (COVID-19) is still debated. Methods: This is an observational, monocentric, and prospective study designed to investigate the incidence, risk factors, and outcomes of MDR bacterial superinfections in COVID-19 patients admitted to the intensive care unit (ICU). Results: A high incidence of superinfections (66%, 159/241) was observed: ventilator-associated pneumonia (VAP) (65%, 104/159) and bloodstream infection (BSI, 32%, 51/159) were the most common. Superinfections, Extra-Corporeal Membrane Oxygenation (ECMO) support, and prone positioning increased the risk of death five, four, and more-than-two times, respectively (OR = 5.431, IC 95%: 1.637-18.014; 4.462, IC 95%: 1.616-12.324 and 2.346, IC 95%: 1.127-4.883). MDR bacteria were identified in 61% of patients with superinfection, with a cumulative incidence of 37.2% at day 14. Carbapenem-resistant Acinetobacter baumannii (CR-AB) and CR-Klebsiella pneumoniae (CR-KP) were the most common causative agents (24.3% and 13.7%). CR-AB was found to significantly increase both ICU and in-hospital mortality (76.4% and 78.2%), whereas CR-KP had no direct impact on mortality. Prior rectal colonization (p < 0.0001), mechanical ventilation (p = 0.0017), a prolonged ICU stay (p < 0.0001), the use of iNO (p = 0.0082), vasopressors (p = 0.0025), curarization (p = 0.0004), and prone positioning (p = 0.0084) were found to be risk factors for CR-AB. Conclusions: Critically ill COVID-19 patients are at high risk of developing MDR superinfection. While CR-KP had no direct impact on mortality, CR-AB appeared to increase ICU and in-hospital mortality.

An integrative review on the risk factors, prevention, and control strategies for carbapenem-resistant Acinetobacter baumannii colonization in critically ill patients

An integrative review on the risk factors, prevention, and control strategies for carbapenem-resistant Acinetobacter baumannii colonization in critically ill patients

Authors’ reply: “Effect of colistin combined with sulbactam: 9 g versus 12 g per day on mortality in the treatment of carbapenems resistant Acinetobacter baumannii pneumonia: a randomized controlled trial”

Authors’ reply: “Effect of colistin combined with sulbactam: 9 g versus 12 g per day on mortality in the treatment of carbapenems resistant Acinetobacter baumannii pneumonia: a randomized controlled trial”

Carbapenem-induced β-lactamase-isoform expression trends in Acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a > 50% fatality rate. Although several resistance mechanisms are understood, it is still impossible to predict which mutations are most likely to occur. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be have some predictability based on structural factors. Additionally, the identified minor isoforms also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe therefore somewhat predictable based on specific structural properties and further investigation may lead to new strategies for mitigating antibiotic resistance.

Activity of cefiderocol in combination with tetracycline analogues against carbapenem-resistant Acinetobacter baumannii

Activity of cefiderocol in combination with tetracycline analogues against carbapenem-resistant Acinetobacter baumannii

Antibiotic Resistance Trends in Carbapenem-Resistant Gram-Negative Pathogens and Eight-Year Surveillance of XDR Bloodstream Infections in a Western Greece Tertiary Hospital.

Background: The increased prevalence of antibiotic resistance among Gram-negative bacteria presents a severe public health challenge, leading to increased mortality rates, prolonged hospital stays, and higher medical costs. In Greece, the issue of multidrug-resistant Gram-negative bacteria is particularly alarming, exacerbated by overuse of antibiotics and inadequate infection control measures. This study aimed to detect the prevalence of extensively drug-resistant (XDR) Gram-negative bacteria in a tertiary hospital in Western Greece over the last eight years from 2016 to 2023. Materials and Methods: In the present study, all Carbapenem-resistant (CR) Acinetobacter baumannii, K. pneumoniae and Pseudomonas aeruginosa. bloodstream isolates from patients hospitalized in the University General Hospital of Patras in Western Greece, from January 2016 to December 2023, were recorded. XDR strains were defined as non-susceptible to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories). The prevalence and distribution of these pathogens across different hospital wards and their susceptibility patterns to key antibiotics (aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, colistin, ampicillin-sulbactam, ceftolozane-tazobactam and ceftazidime-avibactam) were recorded. Results: A total of 1142 blood cultures growing carbapenem-resistant Klebsiella pneumoniae (CRKp), Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPsA) were studied. In the present study, we found an increased resistance of both A. baumannii and K. pneumoniae in colistin. Acinetobacter baumannii had colistin resistance rates between 8.4% and 49.3%, showing a stable increase during the study period. K. pneumoniae showed an increased colistin-resistance rate in 2022 and 2023 (46.8% and 31.2%, respectively) Regarding P. aeruginosa, amikacin was almost inactive with a rate 68.4% and 87.5% in 2020 and 2023, respectively. Of all CR isolates, 69.3% were extensively drug-resistant (XDR). Acinetobacter baumannii had the highest percentage of XDR isolates (34.3%), followed by K. pneumoniae (26.8%) and P. aeruginosa (8.1%). Most XDR pathogens were isolated from the ICU (73.4%), followed by the internal medicine units (64%) and surgical units (22%). Conclusions: The rate of antimicrobial resistance and extensive drug resistance is alarmingly high, which calls for strict surveillance, control measures, and antibiotic stewardship to prevent the development of further resistance.

Pathogenic Burden, Antimicrobial Resistance Pattern and Clinical Outcome of Nosocomial Bloodstream Infections in Intensive Care Unit.

Purpose: Nosocomial bloodstream infections with multidrug-resistant microorganisms have become a common health threat in intensive care settings worldwide. Understanding antimicrobial resistance and the outcomes of these infections is crucial for addressing this issue. This study aimed to investigate the burden, antimicrobial resistance, and 28-day outcomes of nosocomial bloodstream infections in the intensive care unit. Materials and Methods: This retrospective study was conducted in a multispecialty intensive care unit at a tertiary care hospital in western India. Adult patients aged ≥18 years with bloodstream infections acquired after 48 h of admission were included in the analysis. Results: A total of 245 patients suspected of having nosocomial infections in the intensive care unit were evaluated, and 179 were included in the study. Gram-negative bacteremia was identified in the majority of cases, affecting 111 (62%) patients. Carbapenem-resistant Acinetobacter baumannii was the most prevalent pathogen, found in 21.2% (38/179) of patients. Candida species were detected in 37 (20.6%) cases, and gram-positive cocci were identified in 31 (17.3%) patients, with vancomycin-sensitive Enterococci being the most common gram-positive cocci isolated from blood. The central venous catheter was the most frequent source of bloodstream infection, identified in 66 (36.9%) patients. Among all patients, 28-day mortality was observed in 102 (57%) patients. Higher quick sepsis-related organ failure (qSOFA) scores at the onset of bloodstream infection, central venous catheters as a source of infection, inability to initiate early appropriate therapy and septic shock at the onset of bloodstream infection were identified as independent predictors of mortality in patients with nosocomial bloodstream infections. Conclusion: An increased burden of gram-negative bacilli and Candida was found to cause nosocomial bloodstream infections, with very high rates of antimicrobial resistance. Early appropriate diagnosis and treatment play a critical role in improving survival. Additionally, enhanced infection prevention and control practices are necessary to mitigate the heavy burden of infections caused by multidrug-resistant organisms in critical care settings.

Identifying risk factors for carbapenem-resistant Acinetobacter baumannii carriage upon admission: a case-case control study

BackgroundActive screening programs and early detection of asymptomatic carriers are effective in preventing carbapenem-resistant Acinetobacter baumannii (CRAB) dissemination in healthcare facilities. This study aims to identify risk factors associated with CRAB carriage among patients upon admission to an acute care hospital.MethodsA case-case-control study was conducted at an acute care hospital. Starting in June 2020, new admissions to medical wards underwent rectal and buccal screening. Patients with CRAB or carbapenem-susceptible A. baumannii (CSAB) carriage were compared to controls, randomly selected from patients with negative cultures, at a one-to-one ratio. Multinomial logistic regression using a backward stepwise method was employed to identify factors associated with CRAB and CSAB carriage. A Chi-square Automatic Interaction Detector analysis was also conducted to further elucidate risk factors.ResultsThe study included 115 CRAB carriers, 117 CSAB carriers and 121 controls. Increasing age was associated with a reduced risk of CSAB (OR: 0.96, p < 0.001) and CRAB carriage (OR: 0.97, p = 0.02), while higher Charlson Comorbidity Index scores increased the risk for both. CRAB carriage was significantly associated with admission from long-term acute care hospitals (OR: 7.68, p < 0.001) and presence of pressure ulcers (OR: 89.98, p < 0.001). Decision tree analysis identified pressure ulcers, prior location, and Charlson score as key predictors, with CRAB carriage reaching 77.3% in patients admitted from long-term acute care hospitals with pressure ulcers.ConclusionPressure ulcers were strongly associated with the carriage of both susceptible and resistant strains of A. baumannii. CRAB carriage was predominantly observed in patients transferred from long-term acute care hospitals, highlighting the need for targeted screening in this high-risk population.

Efficiency of combination therapy versus monotherapy for the treatment of infections due to carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis

BackgroundFor resistant Gram-positive bacteria, evidence suggests that combination therapy is more effective. However, for resistant Gram-negative bacteria, no consensus has been reached. This study aims to comprehensively summarize the evidence and evaluate the impact of combination versus monotherapy on infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB).MethodsA systematic search was conducted in PubMed, Cochrane library, Web of Science, and Embase up to June 15, 2024, to identify relevant studies. This study included comparisons of monotherapy and combination therapy for treating infections caused by CRGNB. Topical antibiotics (i.e., inhalational or intratracheal administration) and monotherapy with sulbactam/relebactam was excluded. The primary outcome was mortality, and the secondary outcomes were clinical success and microbiological eradication. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated in order to systematically assess effect of treatment on mortality, clinical success and microbiological eradication. Subgroup analyses, publication bias tests, and sensitivity analyses were also performed.ResultsA total of 62 studies, including 8342 participants, were analyzed, comprising 7 randomized controlled trials and 55 non-randomized studies. Monotherapy was associated with higher mortality (OR = 1.29, 95%CI: 1.11–1.51), lower clinical success (OR = 0.74, 95%CI: 0.56–0.98), and lower microbiological eradication (OR = 0.71, 95%CI: 0.55–0.91) compared to combination therapy for CRGNB infections. Specifically, patients with carbapenem-resistant Enterobacteriaceae (CRE) infections receiving monotherapy had higher mortality (OR = 1.50, 95%CI: 1.15–1.95), comparable clinical success (OR = 0.57,95%CI: 0.28–1.16), and lower microbiological eradication (OR = 0.48,95%CI:0.25–0.91) than those receiving combination therapy. For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, no significant differences were observed in mortality (OR = 1.15.95%CI: 0.90–1.47), clinical success (OR = 0.95,95%CI: 0.74–1.24) and microbiological eradication (OR = 0.78,95%CI: 0.54–1.12).ConclusionsMonotherapy or combination therapy is controversial. The systematic review and meta-analysis suggested that monotherapy is associated with higher mortality, lower clinical success, and lower microbiological eradication for treating infection caused by CRGNB. The available evidence suggests that treatment should be selected based on the specific bacteria and antibiotic used. Monotherapy for CRE infections may lead to adverse outcomes. For CRAB infections, no significant differences were found between combination therapy and monotherapy.Systematic review registrationPROSPERO CRD42022331861.

Geographical mapping and temporal trends of Acinetobacter baumannii carbapenem resistance: A comprehensive meta-analysis.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is of critical concern in healthcare settings, leading to limited treatment options. In this study, we conducted a comprehensive meta-analysis to assess the prevalence of CRAB by examining temporal, geographic, and bias-related variations. We systematically searched prominent databases, including Scopus, PubMed, Web of Science, and EMBASE. Quality assessment was performed using the JBI checklist. Subgroup analyses were performed based on the COVID-19 timeframes, years, countries, continents, and bias levels, antimicrobial susceptivity test method and guidelines. Our comprehensive meta-analysis, which included 795 studies across 80 countries from 1995 to 2023, revealed a surge in carbapenem resistance among A. baumannii, imipenem (76.1%), meropenem (73.5%), doripenem (73.0%), ertapenem (83.7%), and carbapenems (74.3%). Temporally, 2020-2023 witnessed significant peaks, particularly in carbapenems (81.0%) and meropenem (80.7%), as confirmed by meta-regression, indicating a steady upward trend. This meta-analysis revealed an alarmingly high resistance rate to CRAB as a global challenge, emphasizing the urgent need for tailored interventions. Transparency, standardized methodologies, and collaboration are crucial for the accurate assessment and maintenance of carbapenem efficacy.

Mayan Medicinal Plants Bignonia potosina and Thouinia paucidentata Demonstrate Anti-Infective Properties Against the Priority Antibiotic-Resistant Bacteria Acinetobacter baumannii and Pseudomonas aeruginosa.

(1) Background: Carbapenem-resistant Acinetobacter baumannii (CBRAB) and Pseudomonas aeruginosa (CBRPA) are critical and high-priority pathogens that require new therapeutic developments. Medicinal plants are valuable pharmaceutical resources. This study explored the anti-infective properties of Mayan plants, Bignonia potosina, and Thouinia paucidentata. (2) Methods: Plant parts were extracted using n-hexane, and their ability to inhibit bacterial growth and counteract resistance mechanisms and virulence factors in CBRAB and CBRPA was assessed. GC-MS analysis of the composition of the non-polar extracts and chemometric techniques correlated the phytoconstituents with anti-infective properties. (3) Results: Bignonia potosina liana and flower extracts exhibited potent antibacterial activity against A. baumannii strains (MIC 15.7 to 250 µg/mL) and moderate activity against P. aeruginosa strains (MIC 250 to 1000 µg/mL). Thouinia paucidentata leaf extract at 1000 µg/mL reduced imipenem MIC by 2048-fold for CBRAB, and B. potosina flower extract significantly inhibited A. baumannii catalase activity (at 62.5 µg/mL) and reduced P. aeruginosa pyocyanin production (at 1000 µg/mL). Chemometric analysis identified fatty acids, fatty acid amides, terpenes, and higher alkanes as contributors to their anti-infective properties. (4) Conclusions: This study highlights the potential of medicinal plants in the development of novel anti-infective therapies against CBRAB and CBRPA with various targets.

Bacteremic nosocomial pneumonia caused by Gram-negative bacilli: results from the nationwide ALARICO study in Italy.

To describe the clinical characteristics and outcomes of patients with nosocomial pneumonia (NP) causedby carbapenem-resistant Gram-negative bacilli (CR-GNB) and to compare them to patients with NP causedby carbapenem-susceptible (CS)-GNB. Prospective observational multicenter study including patients with bacteremic NP caused by GNB from the ALARICO Network (June 2018-January 2020). The primary outcome measure was 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated. Overall, 167 patients with GNB NP were included: 101 with bacteremic NP causedby CR-GNB (n = 39 by KPC-producing Klebsiella pneumoniae, n = 29 by carbapenem-resistant Acinetobacter baumannii, n = 28 by carbapenem-resistant Pseudomonas aeruginosa, n = 5 by MBL-producing Klebsiella pneumoniae) and 66 cases of bacteremic CS-GNB NP. Thirty-day mortality rate was higher in patients with NP causedby CR-GNB compared to those with NPcausedby CS-GNB (46.5% vs 30.3%, p = 0.036). On multivariable analysis, age (HR 1.044, 95% CI 1.021-1.067, p < 0.001), hematological malignancy (HR 4.307, 95% CI 1.924-9.643, p < 0.001) and septic shock (HR 3.668, 95% CI 2.001-6.724, p < 0.001) were factors independently associated with 30-day mortality, while the receipt of adequate antibiotic therapy within 24h from infection onset (HR 0.495, 95% CI 0.252-0.969, p = 0.04) was a protective factor. Carbapenem resistance was not associated with increased risk of mortality (HR 1.075, 95% CI 0.539-2.142, p = 0.837). Patients with bacteremic NP causedby CR-GNB have high mortality rate. Strategies to reduce the time from infection to the administration of adequate antibiotic therapy should be implemented in patients with NP.

OMP38 of Carbapenem-Resistant Acinetobacter Baumannii-Mediated mtDNA Release Activates the cGAS-STING Signaling to Induce Inflammatory Response.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a major threat in the treatment of bacterial infection, and immunotherapy in a non-antibiotic-dependent manner is an effective way to overcome CRAB infection. However, the role of the innate immune response in CRAB infection is poorly understood. Here, it is reported that CRAB infection induced a cytosolic DNA-sensing signaling pathway and significant IFN-β production in mice post-CRAB infection. The knockout of STING reduced bacterial burden, the production of inflammatory cytokines, and lung injury in mice post CRAB infection. The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the adaptor protein stimulator of interferon genes (STING) are required for CRAB-induced IFN-β expression in macrophages. Intriguingly, CRAB utilized outer membrane vesicles (OMVs) to transport outer membrane protein 38 (OMP38) into mitochondria, triggering mitochondrial DNA (mtDNA) release into the cytosol through the mitochondrial permeability transition pore (mPTP) and activating the cGAS-STING signaling. Finally, epigallocatechin gallate (EGCG) is demonstrated to block the activation of the cGAS-STING pathway and ameliorate CRAB-induced excessive inflammatory response. These results demonstrated that the early innate immune response to CRAB infection is activated in a cGAS-STING-dependent manner, which could be a potential therapeutic target for CRAB infection.