calcoaceticus-Acinetobacter Baumannii Research Articles

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.

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.

Prevalence and Resistance Patterns of Urinary Tract Infection in Al-Madinah Al-Munawarah, Saudi Arabia: A Retrospective Study.

Urinary tract infections (UTIs) are among the most common infections and can cause numerous complications of the renal system. This study aimed to assess the prevalence of uropathogens and their antibiotic susceptibility patterns in Al-Madinah Al-Munawarah, Saudi Arabia. Data was collected from patients with UTIs presented at King Fahad General Hospital in Al-Madinah Al-Munawarah, Saudi Arabia. In this retrospective cross-sectional study, UTI microbial-causing agents and antimicrobial resistance profiles identified using automated systems, Phoenix and VITEK2, were collected between July 2022 and June 2023. In addition, minimal demographic data, including date of collection and sex and age of patients were collected and analyzed using Chi-square test. The study included 1394 patients positive for UTI, comprising 50.57% males and 49.43% females (chi-square goodness-of-fit, p > 0.999). Microbial identification and antimicrobial susceptibility tests were performed on UTI-positive cultures. Among UTIs, mono-infection, caused by a single pathogen, was the most prevalent, accounting for 88.16% of cases, whereas poly-infection (caused by multiple pathogens) presented at 11.9%. The most prevalent UTIs' pathogens were E. coli (30.59%), followed by Klebsiella pneumoniae (21.40%), Enterococcus faecalis (8.46%), Pseudomonas aeruginosa (7.81%), Streptococcus agalactiae (6.35%), Enterococcus faecium (3.01%), Proteus mirabilis (3.01%), Enterobacter cloacae (2.52%), Candida sp. (2.44%), Acinetobacter calcoaceticus-baumannii (1.95%), Staphylococcus aureus (1.79%), and Enterobacter aerogenes (1.30%). The most dominant pathogens that coexisted with other uropathogens to cause UTIs were K. pneumoniae and P. mirabilis (9.32%, chi-square 5.550, p = 0.018), K. pneumoniae and P. aeruginosa (8.07%, chi-square 6.285, p = 0.012), K. pneumoniae and E. faecalis (7.45%, chi-square 5.785, p = 0.016), Candida sp. and Enterococcus faecium (4.97%, chi-square 9.176, p = 0.002, and Candida sp. and Acinetobacter calcoaceticus-baumannii (3.11%, chi-square 4.312, p=0.038)). Among the uropathogens, gram-negative pathogens showed resistance to most of the tested antimicrobials (ampicillins, cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, aztreonam, and nitrofurantoin). High rates of resistance were identified to cephalosporins, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole. This study reported UT mono-infection and poly-infection in Al-Madinah Al-Munawarah, Saudi Arabia, with a predominant representation from gram-negative bacteria, Enterobacteriaceae. Most of the UT microbial strains showed a highly resistant profile.

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.

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.

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.

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.

O03 Phenotypic antimicrobial resistance to last-resort antibiotics in carbapenemase-producing bacteria from Ukrainian patients

Abstract Background Since March 2022, there has been an emergence of MDR microorganisms (MDRO) in Europe because of an increasing number of Ukrainian patients with MDRO. The goal was to collect large-scale phenotypic susceptibility data to assess implications for clinical practice. Methods For 122 MDRO (carbapenemase-producing Enterobacterales (CPE, n=96), Pseudomonas aeruginosa CPPA (n=20), carbapenem-resistant Acinetobacter baumannii-calcoaceticus (CRAB, n=6), collected from March to December 2022, broth microdilution (BMD), fosfomycin agar dilution, gradient strip ampicillin/sulbactam, sulbactam/durlobactam, ceftazidime-avibactam-aztreonam and disc diffusion (DD) cefiderocol was performed. Epidemiological data was obtained as part of mandatory reporting by Municipal Health Services (CPE), and surveillance questionnaires (CPPA/CRAB). Results Admission at a Ukrainian hospital in the last year was a risk factor for acquiring MDRO. Of all isolates, 65% (79/122) were blaNDM-positive. For meropenem, aminoglycosides, ceftazidime-avibactam, ceftolozane-tazobactam and imipenem-relebactam susceptibility rates were low (0-30%). For cefiderocol, results depended on reading with or without microcolonies, applying EUCAST or CLSI breakpoints, and whether DD or BMD was used: e.g. for Klebsiella pneumoniae, 30%–97% were susceptible, depending on these variables. For colistin, 103/111 (93%) non-intrinsically resistant CPE/CPPA/CRAB isolates were susceptible. For the majority of CPE, a low MIC of &amp;lt;0.5 mg/L was measured for tigecycline and ceftazidime-avibactam-aztreonam. For CPPA, cefiderocol tested susceptible in 65%–100% of isolates. For CRAB, ampicillin/sulbactam MICs were ≥128 mg/L, for sulbactam/durlobactam 1–2 mg/L. Conclusions There is extensive phenotypic resistance to last-resort antibiotics in carbapenemase-producing bacteria from Ukrainian patients. For cefiderocol, interpretation of susceptibility results depends on a number of variables. In case of infection, treatment options are colistin, cefiderocol (CPE/CPPA/CRAB), tigecycline (CPE/CRAB), ceftazidime-avibactam-aztreonam (CPE), sulbactam/durlobactam (CRAB).

Antimicrobial Susceptibility Profiles of Acinetobacter baumannii Strains, Isolated from Clinical Cases of Companion Animals in Greece.

Acinetobacter baumannii-calcoaceticus (Abc) Complex bacteria are troublesome nosocomial pathogens in human medicine, especially during the last 30 years. Recent research in veterinary medicine also supports its emergence as an animal pathogen. However, relevant data are limited. In this study, we obtained 41 A. baumannii isolates from clinical samples of canine and feline origin collected in veterinary clinics in Greece between 2020 and 2023. Biochemical identification, antimicrobial susceptibility testing, molecular identification and statistical analysis were performed. Most of the samples were of soft tissue and urine origin, while polymicrobial infections were recorded in 29 cases. Minocycline was the most effective in vitro antibiotic, whereas high resistance rates were detected for almost all the agents tested. Notably, 20 isolates were carbapenem resistant and 19 extensively drug resistant (XDR). This is the first report of canine and feline infections caused by Abc in Greece. The results create concerns regarding the capability of the respective bacteria to cause difficult-to-treat infections in pets and persist in veterinary facilities through hospitalized animals, contaminated equipment, and surfaces. Moreover, the prevalence of highly resistant strains in companion animals constitutes a public health issue since they could act as a reservoir, contributing to the spread of epidemic clones in a community.

Supporting Clinical Decisions with Rapid Molecular Diagnostic Pneumonia Panel in Pediatric Intensive Care Unit: Single Center Experience in Turkiye.

Lower respiratory tract infections are the leading cause of morbidity and mortality in children worldwide. It is crucial to promptly conduct diagnostic investigations in order to determine the microbiological cause of pneumonia, since this is necessary to ensure the appropriate delivery of antibiotic therapy to each individual patient. We evaluated the results of a rapid molecular diagnostic pneumonia panel in children with LRTI in a pediatric intensive care unit (PICU). Rapid molecular diagnostic pneumonia panel (BioFire®, FilmArray Pneumonia Panel plus; FA-PP) findings (71 results from 46 children) in a tertiary care PICU between 2019 and 2023 were retrospectively reviewed. At least one bacterial pathogen was detected in 57 cases. A total of 77% of children had underlying conditions. A total of 70.4% of children needed invasive mechanical ventilation and 54.4% had ventilator-associated pneumonia. Pseudomonas aeruginosa (50.8%), Acinetobacter calcoaceticus baumannii complex (42%), and Klebsiella pneumoniae (38.6%) were the most common pathogens detected with the FA-PP. Of the 33 cases diagnosed with VAP, more than one pathogen was identified in 65.9% of cases, with the most commonly identified bacteria being K. pneumoniae (43.1%), P. aeruginosa (38.6%), and Acinetobacter calcoaceticus baumannii complex (31.8%). According to the FA-PP results, the same antibiotic therapy was continued in 39.4% of cases, escalated in 54.5%, and de-escalated in 6.1%. The utilization of the FA-PP has some beneficial effects, including more prompt delivery of findings compared to conventional approaches. Additionally, this approach enables the identification of resistance profiles in children diagnosed with pneumonia in the PICU. Consequently, these test results facilitate the organization of antibiotic treatment strategies, including escalation and de-escalation approaches. The detection of resistance patterns was exclusively determined via the implementation of molecular testing, prompting a reevaluation of the isolation technique in accordance with the obtained data.

Molecular Characterization of Class A-ESBLs, Class B-MBLs, Class C-AmpC, and Class D-OXA Carbapenemases in MDR Acinetobacter baumannii Clinical Isolates in a Tertiary Care Hospital, West Bengal, India.

Background Acinetobacter calcoaceticus baumannii (ACB) complex has become a major concern nowadays because of its increasing involvement in several severe infections associated with catheter-related bloodstream and urinary tract infections, ventilator-associated pneumonia, cerebrospinal shunt-related meningitis, and wound infections. Multiple drug-resistant (MDR) ACB cases have been described with an increasing trend where at least it is resistant to a minimum of three antimicrobial groups. The mortality rate associated with A. baumannii is significantly higher than all Acinetobacterspp. isolates with the most prevalence seen in India and Thailand. The rapid spread of high resistance to most potent antimicrobial drugs is due to its ability to incorporate resistance determinants despite multifactorial reasons such as alteration in permeability of cell membrane by either losing expression of outer membrane porins or excess production of efflux pumps. This study aims to characterize resistance determinants responsible for MDR at the genetic level and emphasizes the use of genotyping in routine diagnosis as genotype analysis is reliable and valid. Methodology A total of 289 ACB complex clinical isolates were included in this study. The study for species-level identification of A. baumannii was conducted at the Department of Microbiology, IQ City Medical College Hospital, Durgapur, West Bengal. In addition, the detection of encoded genes associated with class A-extended spectrum beta-lactamases (i.e., CTX-M, KPC, SHV, and TEM genes), class B-metallo-β-lactamases (i.e., IMP, NDM, and VIM genes), Class C-AmpC cephalosporinase, and classD-OXA carbapenemases (i.e., blaOXA-10/11, blaOXA-24, blaOXA-48, blaOXA-58, blaOXA-143, and blaOXA-235was done using real-time polymerase chain reaction. Results All 289 non-repetitive ACB complex clinical isolates were confirmed as A. baumannii, of which 277 (96%) isolates were MDR. There were no findings of blaCTX-M, blaKPC, blaSHV, blaTEM, blaIMP, blaVIM, blaAmpC, blaOXA-10/11, blaOXA-24, blaOXA-48, blaOXA-58, blaOXA-143, and blaOXA-235 genes in our study. However, there were four (1.44%) positive findings of the blaNDM gene. All MDR isolates (n = 277) were positive for the blaOXA-51 gene. In addition, blaOXA-23 was positive in 269 (97.12%) isolates. Conclusions The oxacillinase production corresponding to blaOXA-23 and blaOXA-51 were the most prevalent antibiotic resistance determinants among MDR A. baumanniiin our study. Four (1.44%) isolates had the multiple genes blaOXA-51, blaOXA-23, and blaNDM that shows the coexistence of diverse genetic elements involved in MDR A. baumannii, resulting in total resistance except for a few potent drugs such as colistin and tigecycline. Genotyping is helpful in determining the contribution of the isolates in understanding their association with encoded genes, which, in turn, helps in designing effective surveillance and control strategies in the management of such MDR isolates.

Biofilm formation in drug-resistant Acinetobacter baumannii and Acinetobacter nosocomialis isolates obtained from a university hospital in Pelotas, RS, Brazil.

This study aimed to investigate the antibiotic resistance and biofilm formation of Acinetobacter calcoaceticus-A. baumannii (ACB) complex isolates recovered from a university hospital in Pelotas, RS, Brazil. The species were confirmed using gyrB multiplex and blaOXA-51-like genes PCR. The presence of the bfmRS virulence gene was evaluated by the PCR, and the isolates were classified based on their biofilm-forming ability on polystyrene (PO) and glass surfaces (TM). Out of 50 ACB complex isolates evaluated, 41 were identified as A. baumannii and nine as A. nosocomialis. The bfmRS gene was detected in 97.6% (40/41) of A. baumannii and 33.3% (3/9) of A. nosocomialis species. Forty-nine isolates exhibited a multidrug-resistant (MDR) profile, while one A. nosocomialis isolate presented an extensively drug-resistant (XDR) profile. All isolates were able of forming biofilms on PO surfaces and 98% (49/50) on TM surfaces. A significant correlation was observed between biofilm production on PO and TM surfaces (P<0.05). However, no correlation was found between biofilms forming and the presence of the bfmRS gene or displaying a certain antibiotic resistance profile. In conclusion, A. baumannii and A. nosocomialis are frequent species causing nosocomial infections in a hospital in Pelotas, RS, Brazil, and both are capable of forming biofilms.

The Microbiological Burden of Short-Term Catheter Reuse in Individuals with Spinal Cord Injury: A Prospective Study.

Despite the risk of developing catheter-associated urinary tract infections (CAUTI), catheter reuse is common among people with spinal cord injury (SCI). This study examined the microbiological burden and catheter surface changes associated with short-term reuse. Ten individuals with chronic SCI reused their catheters over 3 days. Urine and catheter swab cultures were collected daily for analysis. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analyses were used to assess catheter surface changes. Catheter swab cultures showed no growth after 48 h (47.8%), skin flora (28.9%), mixed flora (17.8%), or bacterial growth (5.5%). Asymptomatic bacteriuria was found for most participants at baseline (n = 9) and all at follow-up (n = 10). Urine samples contained Escherichia coli (58%), Klebsiella pneumoniae (30%), Enterococcus faecalis (26%), Acinetobacter calcoaceticus-baumannii (10%), Pseudomonas aeruginosa (6%) or Proteus vulgaris (2%). Most urine cultures showed resistance to one or more antibiotics (62%). SEM images demonstrated structural damage, biofilm and/or bacteria on all reused catheter surfaces. XPS analyses also confirmed the deposition of bacterial biofilm on reused catheters. Catheter surface changes and the presence of antibiotic-resistant bacteria were evident following short-term reuse, which may increase susceptibility to CAUTI in individuals with SCI despite asymptomatic bacteriuria.

Efficacy and safety of sulbactam–durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii–calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK)

An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC. The ATTACK trial was done at 59 clinical sites in 16 countries. Adults aged 18 years or older with ABC-confirmed hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections were randomised 1:1 using a block size of four to sulbactam-durlobactam (1·0 g of each drug in combination over 3 h every 6 h) or colistin (2·5 mg/kg over 30 min every 12 h) for 7-14 days. All patients received imipenem-cilastatin (1·0 g of each drug in combination over 1 h every 6 h) as background therapy. The primary efficacy endpoint was 28-day all-cause mortality in patients with laboratory-confirmed carbapenem-resistant ABC (the carbapenem-resistant ABC microbiologically modified intention-to-treat population). Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference was less than +20%. The primary safety endpoint was incidence of nephrotoxicity assessed using modified Risk, Injury, Failure, Loss, End-stage renal disease criteria measured by creatinine level or glomerular filtration rate through day 42. This trial is registered at ClinicalTrials.gov, NCT03894046. Between Sep 5, 2019, and July 26, 2021, 181 patients were randomly assigned to sulbactam-durlobactam or colistin (176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia; and five bloodstream infections); 125 patients with laboratory-confirmed carbapenem-resistant ABC isolates were included in the primary efficacy analysis. 28-day all-cause mortality was 12 (19%) of 63 in the sulbactam-durlobactam group and 20 (32%) of 62 in the colistin group, a difference of -13·2% (95% CI -30·0 to 3·5), which met criteria for non-inferiority. Incidence of nephrotoxicity was significantly (p<0·001) lower with sulbactam-durlobactam than colistin (12 [13%] of 91 vs 32 [38%] of 85). Serious adverse events were reported in 36 (40%) of 91 patients in the sulbactam-durlobactam group and 42 (49%) of 86 patients in the colistin group. Treatment-related adverse events leading to study drug discontinuation were reported in ten (11%) of 91 patients in the sulbactam-durlobactam group and 14 (16%) of 86 patients in the colistin group. Our data show that sulbactam-durlobactam was non-inferior to colistin, both agents given in combination with imipenem-cilastatin, for the primary endpoint of 28-day all-cause mortality. Sulbactam-durlobactam was well tolerated and could be an effective intervention to reduce mortality from serious infections caused by carbapenem-resistant ABC, including multidrug-resistant strains. Entasis Therapeutics and Zai Lab.

Molecular epidemiology of Acinetobacter baumannii complex causing invasive infections in Korean children during 2001–2020

BackgroundAcinetobacter baumannii (AB) has emerged as one of the most problematic pathogens affecting critically ill patients. This study aimed to investigate the longitudinal epidemiology of AB causing invasive diseases in children.MethodsAcinetobacter spp. cultured from sterile body fluids and identified as Acinetobacter calcoaceticus-baumannii (ACB) complexes by automated systems from children aged below 19 years old were prospectively collected during 2001–2020. The discriminative partial sequence of rpoB gene was sequenced to identify the species, and sequence types (STs) were determined. Temporal changes in antimicrobial susceptibilities and STs were analyzed.ResultsIn total, 108 non-duplicate ACB isolates were obtained from patients with invasive infections. The median age was 1.4 (interquartile range, 0.1–7.9) years, and 60.2% (n = 65) were male. Acinetobacter baumannii comprised 55.6% (n = 60) of the isolates, and the 30-day mortality was higher in patients with isolated AB than in those with non-baumannii Acinetobacter spp. (46.7% vs. 8.3%, P < 0.001). After 2010, complete genotype replacement was observed from non-CC92 genotypes to only CC92 genotypes. Carbapenem resistance rates were highest in AB CC92 (94.2%), followed by AB non-CC92 (12.5%) and non-baumannii Acinetobacter spp. (2.1%). During 2014–2017, which included clustered cases of invasive ST395, colistin resistance increased to 62.5% (n = 10/16), showing a mortality rate of 88% during this period.ConclusionComplete genotype replacement of non-CC92 with CC92 genotypes was observed. AB CC92 was extensively drug-resistant, and pandrug resistance was observed depending on the ST, warranting careful monitoring.

Snapshots of ID Week 2022

Snapshots of ID Week 2022

Evolutionarily stable gene clusters shed light on the common grounds of pathogenicity in the Acinetobacter calcoaceticus-baumannii complex.

Nosocomial pathogens of the Acinetobacter calcoaceticus-baumannii (ACB) complex are a cautionary example for the world-wide spread of multi- and pan-drug resistant bacteria. Aiding the urgent demand for novel therapeutic targets, comparative genomics studies between pathogens and their apathogenic relatives shed light on the genetic basis of human-pathogen interaction. Yet, existing studies are limited in taxonomic scope, sensing of the phylogenetic signal, and resolution by largely analyzing genes independent of their organization in functional gene clusters. Here, we explored more than 3,000 Acinetobacter genomes in a phylogenomic framework integrating orthology-based phylogenetic profiling and microsynteny conservation analyses. We delineate gene clusters in the type strain A. baumannii ATCC 19606 whose evolutionary conservation indicates a functional integration of the subsumed genes. These evolutionarily stable gene clusters (ESGCs) reveal metabolic pathways, transcriptional regulators residing next to their targets but also tie together sub-clusters with distinct functions to form higher-order functional modules. We shortlisted 150 ESGCs that either co-emerged with the pathogenic ACB clade or are preferentially found therein. They provide a high-resolution picture of genetic and functional changes that coincide with the manifestation of the pathogenic phenotype in the ACB clade. Key innovations are the remodeling of the regulatory-effector cascade connecting LuxR/LuxI quorum sensing via an intermediate messenger to biofilm formation, the extension of micronutrient scavenging systems, and the increase of metabolic flexibility by exploiting carbon sources that are provided by the human host. We could show experimentally that only members of the ACB clade use kynurenine as a sole carbon and energy source, a substance produced by humans to fine-tune the antimicrobial innate immune response. In summary, this study provides a rich and unbiased set of novel testable hypotheses on how pathogenic Acinetobacter interact with and ultimately infect their human host. It is a comprehensive resource for future research into novel therapeutic strategies.

Characterizing the Capacity of Acinetobacter calcoaceticusto Grow in Intestinal Conditions and Modulate the Gut Epithelium

BackgroundAcinetobacter species can occupy several ecological niches, including the mammalian intestine. Acinetobacter has been identified in the human fecal microbiota and it is speculated that the gut can serve as a reservoir for this pathobiont. The Acinetobacter calcoaceticus–Acinetobacter baumannii complex is a common cause of drug‐resistant pneumonia, urinary tract, skin and soft tissue infections. A. calcoaceticus has been considered to have relatively low virulence compared to its counterpart A. baumannii since colonization is more frequently noted more than infection clinically. However, few studies have dissected the interaction between A. calcoaceticus and the host, particularly in the gut. In this study, we sought to examine the ability of A. calcoaceticus strains to survive environmental stressors found in the gut. We also examined the reciprocal interactions of A. calcoaceticus strains on the host using colonic organoids.Methods &amp; ResultsThree commercially available strains of A. calcoaceticus and four clinical isolates were grown aerobically in brain heart infusion (BHI) media, subcultured in a fully defined bacterial media termed ZMB1 and exposed to various concentrations of NaCl, ethanol, bile salts and pHs that were designed to mimic the gut. All A. calcoaceticusstrains grew robustly at NaCl concentrations that mirrored the small intestine, but differences were observed between strains at higher NaCl concentrations. Additionally, all strains grew well at pH 7 and pH 6, and exhibited growth reduction at pHs 5 and 4. All strains tolerated several concentrations of bile salts and ethanol; suggesting tolerance for intestinal stressors. Incubation of live A. calcoaceticus strains with inside‐out jejunum and colonic organoids significantly increased pro‐inflammatory cytokines (IL‐1α, KC/IL‐8, MCP‐1 and TNF) and decreased MUC2 and MUC13 transcripts, without altering tight junctions.ConclusionsCollectively, these data demonstrate that A. calcoaceticus is well adapted to the gastrointestinal tract and points to the potential for Acinetobacter to influence the gut epithelium. Of note, we observed differences between lab adapted strains and clinical isolates, highlighting strain variation and indicating that clinical isolate strains should be incorporated into future work.

Elucidating the Antibiotic Resistance of Acinetobacter calcoaceticus Strains

BackgroundAccording to the Center for Disease Control (CDC), antibiotic resistance is one of the largest public health challenges facing modern society. It has been estimated that 2.8 million people each year in the US are infected with an antibiotic‐resistant organism, resulting in &gt;35,000 deaths. One of the multi‐drug resistant microbes listed on the CDC’s urgent threats list is Acinetobacter. The Acinetobacter calcoaceticus–Acinetobacter baumannii complex (ACB complex) is a group of clinically relevant Acinetobacter species that can cause pneumonia, urinary tract, skin and soft tissue infections. Although a lot of work has focused on antibiotic resistance in A. baumannii, the resistance of A. calcoaceticus is underexplored. To address this gap in knowledge, we obtained three commercially available A. calcoaceticus strains and four clinical isolates. We hypothesized that clinical isolates of A. calcoaceticus would be well adapted to withstand traditional antibiotics.Methods &amp; ResultsTo test this hypothesis, we grew commercially available and clinical isolates of A. calcoaceticus in a fully defined bacterial media, termed ZMB1, which was then seeded into Biolog plates (12B) containing beta‐lactams (penicillin G, carbenicillin, oxacillin), tetracyclines (tetracycline, penimepicycline), aminoglycosides (polymyxin B, paromomycin, sisomicin, tobramycin, spectinomycin), glycopeptides (vancomycin), sulfonamides (sulfamethazine, sulfadiazine, sulfathiazole, sulfa‐methoxazole), aminocoumarins (novobiocin), pteridines (2,4‐diamino‐6,7‐ diisopropyl‐ pteridine), biocides (benzethonium chloride), macrolides (spiramycin), antimycobacterials (rifampicin), amphiphiles (dodecyltrimethyl ammonium bromide), and acids (D,L‐Serine hydroxamate, 5‐fluoroorotic acid, L‐aspartic‐β‐ hydroxamate). All A. calcoaceticusstrains were resistant to penicillin G, tetracycline, carbenicillin, and sisomicin. Interestingly, although our commercially available strains were sensitive to sulfamethazine, we observed that all of our clinical isolates were resistant to this antibiotic. We also identified that 2 of our isolates were resistant to polymyxin B and one isolate was highly resistant to dodecyltrimethyl ammonium bromide. These data suggest significant differences in antibiotic resistance between strains.ConclusionsCollectively, these data demonstrate reveal a profile of resistance for A. calcoaceticus. This data also indicates that clinical isolates of A. calcoaceticus are much more resistant to antibiotics than lab adapted strains and should be incorporated into experimental study design.

Positive Bacterial Culture among Lower Respiratory Tract Specimens of Patients in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Lower respiratory tract infection accounts for a great burden of disease worldwide. The problem has further increased due to increasing antimicrobial resistance. This study was done to find out prevalence of positive bacterial culture among lower respiratory tract specimens of patients in a tertiary care centre. A descriptive cross-sectional study was done in the Laboratory of Clinical Microbiology in a tertiary care centre from May, 2021 to October, 2021. Ethical approval was received from the Institutional Review Committee (Reference number: 045-077/078). A total of 635 specimens were collected by convenience sampling. The specimens were cultured as per standard microbiological techniques. Antibiotic susceptibility was performed following Clinical and Laboratory Standards Institute (2020) guidelines. Microsoft Excel was used for data entry and analysis. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion. Among the 635 lower respiratory specimens, 112 (17.63%) (111.97 to 112.03 at 95% Confidence Interval) showed positive bacterial culture. Klebsiella pneumoniae 44 (37.93%) was the commonest isolate followed by Acinetobacter calcoaceticus baumannii complex 34 (29.31%). The prevalence of positive bacterial culture among lower respiratory specimens was lower when compared to other studies done in similar settings. antibiotic resistance; gram negative bacteria; respiratory tract infections.