calcoaceticus-Acinetobacter Baumannii Complex Research Articles

Flexible Development Programs for Antibacterial Drugs to Address Unmet Medical Needs.

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

An overview of sulbactam-durlobactam approval and implications in advancing therapeutics for hospital-acquired and ventilator-associated pneumonia by acinetobacter baumannii-calcoaceticus complex: A narrative review.

Infections caused by Acinetobacter baumannii, particularly those resistant to antibiotics such as carbapenem, have become a global health crisis with a significant mortality rate. Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) resulting from the A. baumannii-calcoaceticus (ABC) complex represent a major clinical challenge. This review aimed to understand the approval process, mechanism of action, therapeutic potential, and future implications of sulbactam-durlobactam therapy (SUL-DUR). PubMed, Web of Science, EMBASE, Clinical trials. gov, ICTRP, and CENTRAL were searched for studies on SUL-DUR for the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia. Also, World Health Organization, U.S. Food and Drug Administration, and Centers for Disease Control and Prevention websites were searched for relevant information. SUL-DUR, marketed as Xacduro, is a novel pharmaceutical combination that functions as a narrow-spectrum parenterally administered antibiotic. Sulbactam acts as a β-lactamase inhibitor, whereas durlobactam protects against degradation by A. baumannii enzymes. A phase 1 trial successfully established the safety and tolerability of SUL-DUR in patients with normal and mild renal impairment. A phase 2 trial demonstrated the safety and tolerability of SUL-DUR in a larger population with urinary tract infections. A phase 3 trial showed that SUL-DUR was non-inferior to colistin in terms of mortality in A. baumannii-related VAP, HAP, and bacteremia. The combination of sulbactam and durlobactam is a promising treatment option for HAP and VAP caused by ABC complex.

Rapid species differentiation and typing of Acinetobacter baumannii

Acinetobacter (A.) baumannii has emerged as a difficult-to-treat nosocomial bacterial human pathogen. A. baumannii is to be dealt with under the “One Health” approach, and its surveillance in human, animal, and environmental settings assumes paramount importance in understanding its plausible transmission dynamics. Accurate identification of A. baumannii, its clonal complexes, and sequence types is important for understanding the epidemiological distribution, evolutionary relationships, and transmission dynamics. A wide range of genotyping techniques are applied for the differentiation of the Acinetobacter calcoaceticus-baumannii (ACB) complex. However, there is no single straight-forward genotype method applied for rapid assays. Currently, two multilocus sequence typing (MLST) Oxford and Pasture schemes exist; though considered a gold standard for sequence typing, harmonizing the schemes is not a straightforward process. The whole genome sequencing-based core-genome multilocus sequence typing (cgMLST) and core single nucleotide polymorphism (cgSNP) are robust and precise sequence typing; however, they are expensive, depending on the quality of sequencing and demand a higher level of computational skills. In the past decade, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) based species identification has been successfully employed for rapid discrimination of the ACB complex. MALDI typing is rapid, easier, cheaper, and as reliable as molecular methods. Strain level A. baumannii identification confidence improved upon augmentation of existing databases with in-house reference spectra of well-defined isolates. The application of artificial intelligence and machine learning might be useful in clonal sequence types (ST)-level identification. The genus Acinetobacter’s taxonomic classification is evolving, and newer STs are being described; hence, the establishment of a central repository of A. baumannii reference spectra will help in harmonizing across the laboratories and help in the global level surveillance program on A. baumannii in “One Health” perspective. This review sheds light on the challenges related to techniques employed for the identification of Acinetobacter and the potential application and future perspectives of MALDI-TOF MS.

Molecular typing of reduced susceptibility of Acinetobacter calcoaceticus-baumannii complex to Chlorhexidine in Turkey by pulsed-field gel electrophoresis.

Introduction. The global spread of Acinetobacter spp., particularly the Acinetobacter calcoaceticusbaumannii (ACB) complex, has led to its recognition as a significant pathogen by the World Health Organization (WHO). The increasing resistance of the ACB complex to multiple antibiotics presents a challenge for treatment, necessitating accurate antibiotic susceptibility profiling after isolation.Hypothesis or gap statement. There is limited understanding of the antimicrobial resistance and chlorhexidine, a biocide, susceptibility profiles of ACB complex strains, especially in clinical settings in Turkey.Aim. This study aimed to identify ACB complex strains recovered from various clinical specimens at Hacettepe University Hospitals in Ankara, Turkey, in 2019, and to assess identification, their antibiotic and chlorhexidine susceptibility profiles, and genomic relatedness.Methodology. Eighty-two ACB complex strains were identified using MALDI-TOF MS. Susceptibility testing to 12 antibiotics was conducted using the disc diffusion method, and colistin, chlorhexidine susceptibility was assessed using the broth microdilution technique, following the latest EUCAST and CLSI guidelines. ACB complex members with reduced chlorhexidine sensitivity were further analyzed by pulsed-field gel electrophoresis (PFGE) for bacterial typing.Results. Among the isolates, 1.2% were multidrug-resistant (MDR), 73.2% were extensively drug-resistant (XDR), and 12.2% were pandrug-resistant (PDR). Carbapenem resistance was found in 86.7% of MDR, PDR, and XDR strains. Colistin resistance was observed in 15.8% of isolates, and 18.2% exhibited decreased susceptibility to chlorhexidine. PFGE revealed seven different clones among strains with reduced chlorhexidine sensitivity, indicating vertical transmission within the hospital.Conclusion. This study highlights the reduced susceptibility to chlorhexidine in ACB complex members and provides epidemiological insights into their spread. The findings underscore the importance of screening for antimicrobial resistance and biocide susceptibility profiles to effectively manage healthcare-associated infections.

Application of LAMP assay for detection of carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex in ICU admitted sepsis patients: A rapid and cost-effective diagnostic tool

Carbapenem-resistant significant members of Acinetobacter calcoaceticus–Acinetobacter baumannii (CR-SM-ACB) complex have emerged as an important cause of sepsis, especially in ICUs. This study demonstrates the application of loop-mediated-isothermal-amplification (LAMP) assay for detection of CR-SM-ACB-complex from patients with sepsis.Whole-blood and culture-broths(CB) collected from patients with culture-positive sepsis were subjected to LAMP and compared with PCR, and RealAmp. Vitek-2 system and conventional PCR results were used as confirmatory references.The sensitivity and specificity of LAMP(97 % & 100 %) and RealAmp(100 % & 100 %) for detection of CR-SM-ACB-complex from CB were better than PCR(87 % & 100 %). Diagnostic accuracy of LAMP, RealAmp, and PCR for detection of SM-ACB-complex from CB was 98.5 %, 100 %, and 88.5 % respectively. Turnaround time of Culture, LAMP, PCR, and RealAmp was 28-53, 6-20, 9-23, and 6-20hours, respectively.LAMP is a simple, inexpensive tool that can be applied directly to positive CB and may be customized to detect emerging pathogens and locally-prevalent resistance genes and to optimize antimicrobial use.

The real-world impact of the BioFire FilmArray blood culture identification 2 panel on antimicrobial stewardship among patients with bloodstream infections in intensive care units with a high burden of drug-resistant pathogens

BackgroundThe increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored. MethodsThis retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists. ResultsA total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p < 0.001). BCID2 demonstrated 100% concordance in genotype–phenotype correlation in antimicrobial resistance (AMR) for CRKP, carbapenem-resistant Escherichia coli, MRSA, and VRE. A total of 40.5% of patients received inadequate empirical antimicrobial treatment. The antimicrobial regimen was adjusted or confirmed in 55.4% of patients following the BCID2 results. ConclusionsIn the context of a high burden of drug-resistant pathogens, BCID2 demonstrated rapid pathogen and AMR detection, with a noticeable impact on antimicrobial stewardship in BSI in the ICU.

In vitro antibacterial activity of sulbactam-durlobactam in combination with other antimicrobial agents against Acinetobacter baumannii-calcoaceticus complex

Combinations of the β-lactam/β-lactamase inhibitor sulbactam-durlobactam and seventeen antimicrobial agents were tested against strains of Acinetobacter baumannii in checkerboard assays. Most combinations resulted in indifference with no instances of antagonism. These results suggest sulbactam-durlobactam antibacterial activity against A. baumannii is unlikely to be affected if co-dosed with other antimicrobial agents.

Evidence and antibiotic resistance profiles of clinical Acinetobacter calcoaceticus-Acinetobacter baumannii (ACB) and non-ACB complex members in companion animals: A 2020–2022 retrospective study

To evaluate the frequency of Acinetobacter spp., belonging to both Acinetobacter calcoaceticus-baumannii (ACB) and non-ACB complex, and their antibiotic resistance profiles in veterinary medicine, a three-year (2020–2022) retrospective study was carried out on sick companion animals. Epidemiological data from different clinical canine, feline, and equine samples, were acquired. For each strain, MALDI-TOF MS identification and susceptibility to a panel of 11 antibiotics, by Kirby-Bauer and E-test methods, were performed. Out of 628 bacteriological examinations, 2.5% resulted positive for strains belonging to Acinetobacter genus. Frequencies of 2.3%, 1.9%, and 3% were obtained from both in-visiting and hospitalized dogs, cats, and horses, respectively. Members of ACB-complex accounted for 50% of isolates. Since all strains resulted susceptible to aminoglycosides and polymyxins, no pandrug-resistant (PDR) species were recorded. While 12.5% A. baumannii resulted extensively-drug resistant (XDR), a higher percentage of multidrug-resistant strains was recorded among non-ACB strains (35.5%) than ACB strains (25%). Susceptibility was observed in the same percentage in both groups (62.5%). All ACB strains confirmed their intrinsic resistances. Non-ACB species showed lower resistances against antipseudomonal penicillins plus beta-lactamase inhibitors (P=0.1306), III generation cephalosporins (P=0.0547), and tetracyclines (P=0.0209) than ACB species. Carbapenem-resistance was observed for XDR A. baumannii (12.5%) and, in particular for MDR non-ACB complex members (25%). To our knowledge, A. lactucae represents the first description in two sick dogs in Italy. Furthermore, our results emphasize the role of non-ACB-complex species as important zoonotic pathogens, which could be reservoirs of clinically relevant resistance profiles.

Antibacterial activity of deer musk and Ziziphus spina-christi against carbapebem resis-tant gram negative bacteria isolated from patients with burns and wounds

Bacteria were isolated from 250 specimens obtained from patients attending the Plastic Reconstructive and Burn Surgery Hospital in the Sulaymaniyah (Kurdistan region) and the burn and wound care units of the Azadi Teaching Hospital (Kirkuk), Iraq. Gram-negative bacteria were isolated from 100 (40%) of the samples which identified by BD phoenix, 66 isolates (66%) were carbapenem-resistant species, Rapidec® Carba NP test and sensitivity tests revealed 17 different genera and species of carbapenem-resistant bacteria. The BD Phoenix system was used to evaluate the susceptibility test of the isolates to 18 different antibiotics. The number of isolates that exhibited resistance to the carbapenem antibiotics, ertapenem, imipenem and meropenem, was 40 (61%), 35 (54%) and 28 (42%) respectively. Meanwhile, the number of isolates resistant to the penicillin antibiotics, ampicillin, amoxicillin-clavulanic acid and piperacillin-tazobactam, was 61 (92%), 54 (82%) and 24 (36%) respectively. The isolates were also evaluated for their resistance to the cephalosporins, cefazolin, cefuroxime, ceftazidime, ceftriaxone, cefepime, and ceftolozane-tazobactam; the respective number of resistant isolates were 60 (91%), 60 (91%), 39 (59%), 48 (73%), 42 (64%) and 27(41%). In contrast, a fraction of Ziziphus spina-christi leaves that was extracted using ethyl acetate inhibited all of the carbapenem-resistant isolates studied. The zone of inhibition (ZoI) Ø was between 19 and 24 mm. The ZoI Ø of black deer musk was 11–19 mm. The minimum inhibitory concentration (MICs) of ethyl acetate extract of Ziziphus spina-christi leaves for Acinetobacter baumannii (PDR), CR-Citrobacter farmeri, CR-Escherichia coli, CR-Proteus mirabilis, CR-Pseudomonas fluorescens, CR-Escherichia vulneris, CR-Kluyvera ascorbata, CR-Pantoea agglomerans, CR-Pseudomonas putida and CR-Serratia marcescens, was 6.25 mg/mL. Meanwhile, the MIC for Acinetobacter calcoaceticus–baumannii complex, Citrobacter freundii, Enterobacter cloacae, Klebsiella pneumoniae, Morganella morganii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia was 12.5 mg/mL. High-performance liquid chromatography (HPLC) was used to analyse the components of the ethyl acetate-extract of Ziziphus spina-christi leaves. The analysis found gallic acid (760.3 ppm/mL), caffeine (84.0 ppm/mL) and quercetin (2.2 ppm/mL); the total phenolic content was 846.5 ppm/mL. The evidence obtained from this study indicates that leaves of this plant (named sidr in the Middle East) have the potential to be used as a natural antibiotic against carbapenem-resistant Gram-negative bacteria. Thus, the leaves of this tree present an important opportunity in the development of novel therapeutic agents. The study found the MIC of deer musk for CR-Citrobacter farmeri, CR-Citrobacter freundii, CR-Enterobacter cloacae, CR-Escherichia vulneris, CR-Klebsiella pneumoniae, CR-Kluyvera ascorbata, CR-Morganella morganii, CR-Pantoea agglomerans, CR-Proteus mirabilis, CR-Pseudomonas fluorescens, CR-Pseudomonas putida and CR-Serratia marcescens to be 50 mg/mL. In contrast, the MIC of deer musk was 100 mg/mL for Acinetobacter baumannii (PDR), CR-Acinetobacter calcoaceticus–baumannii complex, CR-Escherichia coli, CR-Pseudomonas aeruginosa and CR-Stenotrophomonas maltophilia. The results of the gas chromatography–mass spectrometry (GC–MS) indicate that the primary constituents of musk were1,4,4-tetramethyltetralin, 7-acetyl-6-ethyl-1, diethyl phthalate and tonalid; their contribution to the whole ranged from 12.2% to 19.6%. Black musk exhibits considerable antibacterial activity, able to inhibit seventeen different species of carbapenem-resistant Gram-negative bacteria. The non-natural form of black musk can be used to scent detergent.

A bioinformatic approach to identify confirmed and probable CRISPR-Cas systems in the Acinetobacter calcoaceticus-Acinetobacter baumannii complex genomes.

The Acinetobacter calcoaceticus-Acinetobacter baumannii complex, or Acb complex, consists of six species: Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter seifertii, and Acinetobacter lactucae. A. baumannii is the most clinically significant of these species and is frequently related to healthcare-associated infections (HCAIs). Clustered regularly interspaced short palindromic repeat (CRISPR) arrays and associated genes (cas) constitute bacterial adaptive immune systems and function as variable genetic elements. This study aimed to conduct a genomic analysis of Acb complex genomes available in databases to describe and characterize CRISPR systems and cas genes. Acb complex genomes available in the NCBI and BV-BRC databases, the identification and characterization of CRISPR-Cas systems were performed using CRISPRCasFinder, CRISPRminer, and CRISPRDetect. Sequence types (STs) were determined using the Oxford scheme and ribosomal multilocus sequence typing (rMLST). Prophages were identified using PHASTER and Prophage Hunter. A total of 293 genomes representing six Acb species exhibited CRISPR-related sequences. These genomes originate from various sources, including clinical specimens, animals, medical devices, and environmental samples. Sequence typing identified 145 ribosomal multilocus sequence types (rSTs). CRISPR-Cas systems were confirmed in 26.3% of the genomes, classified as subtypes I-Fa, I-Fb and I-Fv. Probable CRISPR arrays and cas genes associated with CRISPR-Cas subtypes III-A, I-B, and III-B were also detected. Some of the CRISPR-Cas systems are associated with genomic regions related to Cap4 proteins, and toxin-antitoxin systems. Moreover, prophage sequences were prevalent in 68.9% of the genomes. Analysis revealed a connection between these prophages and CRISPR-Cas systems, indicating an ongoing arms race between the bacteria and their bacteriophages. Furthermore, proteins associated with anti-CRISPR systems, such as AcrF11 and AcrF7, were identified in the A. baumannii and A. pittii genomes. This study elucidates CRISPR-Cas systems and defense mechanisms within the Acb complex, highlighting their diverse distribution and interactions with prophages and other genetic elements. This study also provides valuable insights into the evolution and adaptation of these microorganisms in various environments and clinical settings.

Differentiation of closely-related species within Acinetobacter baumannii-calcoaceticus complex via Raman spectroscopy: a comparative machine learning analysis.

Bacterial species within the Acinetobacter baumannii-calcoaceticus (Acb) complex are very similar and are difficult to discriminate. Misidentification of these species in human infection may lead to severe consequences in clinical settings. Therefore, it is important to accurately discriminate these pathogens within the Acb complex. Raman spectroscopy is a simple method that has been widely studied for bacterial identification with high similarities. In this study, we combined surfaced-enhanced Raman spectroscopy (SERS) with a set of machine learning algorithms for identifying species within the Acb complex. According to the results, the support vector machine (SVM) model achieved the best prediction accuracy at 98.33% with a fivefold cross-validation rate of 96.73%. Taken together, this study confirms that the SERS-SVM method provides a convenient way to discriminate between A. baumannii, Acinetobacter pittii, and Acinetobacter nosocomialis in the Acb complex, which shows an application potential for species identification of Acinetobacter baumannii-calcoaceticus complex in clinical settings in near future.

Tracing clinically-relevant antimicrobial resistances in Acinetobacter baumannii-calcoaceticus complex across diverse environments: A study spanning clinical, livestock, and wastewater treatment settings

Acinetobacter baumannii has become a prominent nosocomial pathogen, primarily owing to its remarkable ability to rapidly acquire resistance to a wide range of antimicrobial agents and its ability to persist in diverse environments. However, there is a lack of data on the molecular epidemiology and its potential implications for public health of A. baumannii strains exhibiting clinically significant resistances that originate from non-clinical environments.Therefore, the genetic characteristics and resistance mechanisms of 80 A. baumannii-calcoaceticus (ABC) complex isolates, sourced from environments associated with poultry and pig production, municipal wastewater treatment plants (WWTPs), and clinical settings, were investigated.In total, our study classified 54 isolates into 29 previously described sequence types (STs), while 26 isolates exhibited as-yet-unassigned STs. We identified a broad range of A. baumannii STs originating from poultry and pig production environments (e.g., ST10, ST238, ST240, ST267, ST345, ST370, ST372, ST1112 according to Pasteur scheme). These STs have also been documented in clinical settings worldwide, highlighting their clinical significance. These findings also raise concerns about the potential zoonotic transmission of certain STs associated with livestock environments. Furthermore, we observed that clinical isolates exhibited the highest diversity of antimicrobial resistance genes (ARGs). In contrast to non-clinical isolates, clinical isolates typically carried a significantly higher number of ARGs, ranging from 10 to 15. They were also the exclusive carriers of biocide resistance genes and acquired carbapenemases (blaOXA-23, blaOXA-58, blaOXA-72, blaGIM-1, blaNDM-1). Additionally, we observed that clinical strains displayed an increased capacity for carrying plasmids and undergoing genetic transformation. This heightened capability could be linked to the intense selective pressures commonly found within clinical settings.Our study provides comprehensive insights into essential aspects of ABC isolates originating from livestock-associated environments and clinical settings. We explored their resistance mechanisms and potential implications for public health, providing valuable knowledge for addressing these critical issues.

Clinical Outcomes for Patients With Monomicrobial vs Polymicrobial Acinetobacter baumannii-calcoaceticus Complex Infections Treated With Sulbactam-Durlobactam or Colistin: A Subset Analysis From a Phase 3 Clinical Trial.

In a previous study, the efficacy and safety of sulbactam-durlobactam vs colistin for the treatment of patients with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRABC) infections were evaluated in a randomized controlled phase 3 trial. Both arms were dosed on a background of imipenem-cilastatin to treat coinfecting gram-negative pathogens. Thirty-six percent of infections in the primary efficacy population were polymicrobial. A subset analysis was performed to compare clinical and microbiological outcomes at test of cure (7 ± 2 days after the last dose) for patients with monomicrobial and polymicrobial CRABC infections. Minimal inhibitory concentrations of antibiotics against baseline isolates were determined by broth microdilution according to Clinical and Laboratory Standards Institute methodology. Clinical cure, 28-day all-cause mortality, and microbiological outcomes were similar for patients in the sulbactam-durlobactam treatment arm with monomicrobial or polymicrobial A baumannii-calcoaceticus infections. Patients in the colistin arm with monomicrobial CRABC infections had higher mortality rates with worse clinical and microbiological outcomes as compared with those with polymicrobial infections. For patients who received sulbactam-durlobactam, imipenem susceptibility of coinfecting gram-negative pathogens trended with clinical benefit for patients with polymicrobial A baumannii-calcoaceticus infections. When tested in vitro, durlobactam restored imipenem susceptibility to the majority of coinfecting gram-negative pathogens from the sulbactam-durlobactam arm. This phenotype appeared to be related to the clinical outcome in 13 of 15 evaluable cases. These results suggest that the use of sulbactam-durlobactam plus a carbapenem could be an effective approach to treat polymicrobial infections that include CRABC, but additional clinical data are needed to demonstrate efficacy.

Antimicrobial resistance of clinical bacterial isolates in China: current status and trends.

Antimicrobial resistance surveillance systems have been established in China. Two representative national surveillance networks are the China Antimicrobial Surveillance Network (CHINET) and China Antimicrobial Resistance Surveillance System (CARSS), both of which were established in 2005. For all clinical isolates collected in both of these surveillance networks, the ratio of Gram-negative bacilli to Gram-positive cocci was approximately 7:3 during the past 18 years. Generally, Gram-negative bacilli have a higher antimicrobial resistance profile in China. The prevalence of ESBLs in Escherichia coli is as high as approximately 50%. Acinetobacter baumannii-calcoaceticus complex (ABC) has a high antimicrobial resistance profile, with a carbapenem resistance rate of approximately 66%. However, the prevalence of carbapenem-resistant ABC has also shown a decreasing trend from 2018 to 2022. The prevalence of vancomycin-resistant Enterococcus was low, and the prevalence of MRSA and carbapenem-resistant Pseudomonas aeruginosa showed decreasing trends from 2005 to 2022. CHINET surveillance data demonstrated that the prevalence of carbapenem-resistant Klebsiella pneumoniae showed a remarkable increasing trend from 2.9% (imipenem resistance) in 2005 to 25.0% in 2018, and then slightly decreased to 22.6% in 2022. The decreasing trends may reflect the antimicrobial stewardship efforts in China: a professional consensus on the rational clinical use of carbapenems was issued by the National Health Commission of China and was well implemented nationally; after that, the clinical use of carbapenems decreased slightly in China.

Three novel multiplex PCR assays for rapid detection of virulence, antimicrobial resistance, and toxin genes in Acinetobacter calcoaceticus-baumannii complex species.

The Acinetobacter calcoaceticus-baumannii (ACB) complex is an often-overlooked group of nosocomial pathogens with a significant environmental presence. Rapid molecular screening methods for virulence, antimicrobial resistance, and toxin (VAT) genes are required to investigate the potential pathogenicity of environmental isolates. This study aimed to develop and apply novel ACB complex-specific multiplex PCR (mPCR) primers and protocols for the rapid detection of eight VAT genes. We optimized three single-tube mPCR assays using reference DNA from ACB complex and other Acinetobacter species. These assays were then applied to detect VAT genes in cultured ACB complex isolates recovered from clinical and environmental sources. Widespread detection of VAT genes in environmental isolates confirmed the validity, functionality, and applicability of these novel assays. Overall, the three newly developed ACB complex species-specific mPCR assays are rapid and simple tools that can be adopted in diagnostic and clinical lab settings. The detection of VAT genes in environmental isolates suggests that environmental niches could serve as a reservoir for potentially pathogenic ACB complex and warrants further investigation. The newly developed mPCR assays are specific, sensitive, and efficient, making them well-suited for high-throughput screening in epidemiological studies and evaluating the potential pathogenicity of ACB complex recovered from various sources.

Sulbactam-durlobactam: a β-lactam/β-lactamase inhibitor combination targeting Acinetobacter baumannii.

Sulbactam-durlobactam is a pathogen-targeted β-lactam/β-lactamase inhibitor combination that has been approved by the US FDA for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex (ABC) in patients 18years of age and older. Sulbactam is a penicillin derivative with antibacterial activity against Acinetobacter but is prone to hydrolysis by β-lactamases encoded by contemporary isolates. Durlobactam is a diazabicyclooctane β-lactamase inhibitor with activity against Ambler classes A, C and D serine β-lactamases that restores sulbactam activity both in vitro and in vivo against multidrug-resistant ABC. Sulbactam-durlobactam is a promising alternative therapy for the treatment of serious Acinetobacter infections, which can have high rates of mortality.

Dynamic monitoring of neutrophil/lymphocyte ratio, APACHE II score, and SOFA score predict prognosis and drug resistance in patients with Acinetobacter baumannii-calcoaceticus complex bloodstream infection: a single-center retrospective study.

This study aimed to evaluate the clinical value of dynamic monitoring of neutrophil/lymphocyte ratio (NLR), APACHE II (Acute Physiology and Chronic Health Evaluation II) score, and Sequential Organ Failure Assessment (SOFA) score in predicting 28-day prognosis and drug resistance in patients with bloodstream infection with Acinetobacter baumannii-calcoaceticus complex (Abc complex). In this research, individuals admitted to Tianjin Medical University General Hospital from January 2017 to March 2023 with bloodstream infections and a minimum of one Abc complex positive blood culture were chosen. The risk factors for the 28-day prognosis and drug resistance were analyzed using logistic regression. The NLR, APACHE II score, and SOFA score were evaluated for predicting 28-day prognosis and drug resistance using an ROC curve analysis. The data were analyzed using R Studio to find correlations and conduct survival analysis with the Kaplan-Meier method. The final statistical analysis included a total of 129 patients with bloodstream infections caused by Abc complex. Independent risk factors predicting mortality within 28 days were identified as follows: the SOFA score and APACHE II scores at 24 h, and APACHE II scores at 72 h after the onset of blood infection (p < 0.05). NLR, SOFA score, and APACHE II score did not predict drug resistance. Patients with Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) had shorter survival times than those with carbapenem-sensitive strains (40.77 days vs. 47.65 days, respectively, p = 0.0032). The prognosis of Abc complex bloodstream infection is affected by both SOFA and APACHE II scores. Both scoring systems have similar prognostic values at different time points after infection, but for computational convenience, it is recommended to use the SOFA score. NLR exhibits limited effectiveness in predicting mortality within 28 days. Carbapenem-resistant individuals with Abc complex experience significantly reduced survival time. None of the three factors-SOFA score, APACHE II score, and NLR-can early predict the occurrence of CRAB infections effectively.

Carbapenem Resistance in Acinetobacter calcoaceticus-baumannii Complex Isolates From Kathmandu Model Hospital, Nepal, Is Attributed to the Presence of bla OXA-23-like and bla NDM-1 Genes.

The Acinetobacter calcoaceticus-baumannii (ACB) complex, also known as ACB complex, consists of four bacterial species that can cause opportunistic infections in humans, especially in hospital settings. Conventional therapies for susceptible strains of the ACB complex include broad-spectrum cephalosporins, β-lactam/β-lactamase inhibitors, and carbapenems. Unfortunately, the effectiveness of these antibiotics has declined due to increasing rates of resistance. The predominant resistance mechanisms identified in the ACB complex involve carbapenem-resistant (CR) oxacillinases and metallo-β-lactamases (MBLs). This research, conducted at Kathmandu Model Hospital in Nepal, sought to identify genes associated with CR, specifically blaNDM-1, blaOXA-23-like, and blaOXA-24-like genes in carbapenem-resistant Acinetobacter calcoaceticus-baumannii (CR-ACB) complex. Additionally, the study is aimed at identifying the ACB complex through the sequencing of the 16s rRNA gene. Among the 992 samples collected from hospitalized patients, 43 (approximately 4.334%) tested positive for the ACB complex. These positive samples were mainly obtained from different hospital units, including intensive care units (ICUs); cabins; and neonatal, general, and maternity wards. The prevalence of infection was higher among males (58.14%) than females (41.86%), with the 40-50 age group showing the highest infection rate. In susceptibility testing, colistin and polymyxin B exhibited a susceptibility rate of 100%, whereas all samples showed resistance to third-generation cephalosporins. After polymyxins, gentamicin (30.23%) and amikacin (34.88%) demonstrated the highest susceptibility. A substantial majority (81.45%) of ACB complex isolates displayed resistance to carbapenems, with respiratory and pus specimens being the primary sources. Polymerase chain reaction (PCR) revealed that the primary CR gene within the ACB complex at this hospital was bla OXA-23-like, followed by bla NDM-1. To ensure the accuracy of the phenotypic assessment, 12 samples were chosen for 16s rRNA sequencing using Illumina MiSeq™ to confirm that they are Acinetobacter species. QIIME 2.0 analysis confirmed all 12 isolates to be Acinetobacter species. In the hospital setting, a substantial portion of the ACB complex carries CR genes, rendering carbapenem ineffective for treatment.

Evaluation of the BioFire FilmArray Pneumonia Panel Plus for Detection of Viral, Bacterial Pathogens and Antimicrobial Resistance Genes in Lower Respiratory Tract Specimens at Al-Zahra Hospital for Pediatrics in Najaf, Iraq

The study aimed to evaluate the BioFire FilmArray Pneumonia Panel (BFPP) in rapidly diagnosing pathogens and detecting antimicrobial resistance genes in pediatric respiratory specimens, with an aim to enhance clinical decision-making in a pediatric hospital in Najaf, Iraq. For a period from 24/11/2022 to 22/5/2023, 36 specimens from pediatric patients with lower respiratory tract infection of males and females of different ages less than six years were collected. All specimens met the inclusion criteria, where Procalcitonin (PCT) levels above 0.5 ng/ml and negative blood cultures. The most prevalent pathogen detected were Acinetobacter calcoaceticus-baumannii complex in 63.89% of samples. Staphylococcus aureus and Klebsiella pneumoniae were detected in 44.44% and 41.67% of specimens, respectively. Less frequent were Streptococcus pneumoniae and Escherichia coli at 19.44%, Pseudomonas aeruginosa at 16.67%, Haemophilus influenzae at 11.11%, and Moraxella catarrhalis and Serratia marcescens each at 5.56%. Adenovirus was the most frequently detected virus, in 33.33% of the total samples. Other viruses detected include Human Rhinovirus/Enterovirus 19.44%, Respiratory Syncytial Virus 16.66%, Parainfluenza 11.11%, Human Metapneumovirus and Influenza B account for 5.55% while Corona virus not detected at all specimens. VIM gene was found in 63.89% of specimens, underscoring extensive carbapenem resistance, while other resistance genes appeared sporadically like mecA/C in 13.88%, IMP in 5.55% and KPC in 2.77 while OXA-48 like not detected at all.

Antimicrobial resistance genes harbored in invasive Acinetobacter calcoaceticus-baumannii complex isolated from Korean children during the pre-COVID-19 pandemic periods, 2015-2020.

Acinetobacter baumannii (AB) has emerged as one of the most challenging pathogens worldwide, causing invasive infections in the critically ill patients due to their ability to rapidly acquire resistance to antibiotics. This study aimed to analyze antibiotic resistance genes harbored in AB and non-baumannii Acinetobacter calcoaceticus-baumannii (NB-ACB) complex causing invasive diseases in Korean children. ACB complexes isolated from sterile body fluid of children in three referral hospitals were prospectively collected. Colistin susceptibility was additionally tested via broth microdilution. Whole genome sequencing was performed and antibiotic resistance genes were analyzed. During January 2015 to December 2020, a total of 67 ACB complexes were isolated from sterile body fluid of children in three referral hospitals. The median age of the patients was 0.6 (interquartile range, 0.1-7.2) years old. Among all the isolates, 73.1% (n=49) were confirmed as AB and others as NB-ACB complex by whole genome sequencing. Among the AB isolates, only 22.4% susceptible to carbapenem. In particular, all clonal complex (CC) 92 AB (n=33) showed multi-drug resistance, whereas 31.3% in non-CC92 AB (n=16) (P<0.001). NB-ACB showed 100% susceptibility to all classes of antibiotics except 3rd generation cephalosporin (72.2%). The main mechanism of carbapenem resistance in AB was the bla oxa23 gene with ISAba1 insertion sequence upstream. Presence of pmr gene and/or mutation of lpxA/C gene were not correlated with the phenotype of colistin resistance of ACB. All AB and NB-ACB isolates carried the abe and ade multidrug efflux pumps. In conclusion, monitoring and research for resistome in ACB complex is needed to identify and manage drug-resistant AB, particularly CC92 AB carrying the bla oxa23 gene.