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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. [ABSTRACT FROM AUTHOR]

Purpose: Predicting infection risk in carbapenem-resistant Acinetobacter baumannii (CRAB) colonized patients may help in improving timely appropriate antibiotic therapy. This study aims to explore risk factors for developing infections in hospitalized patients with previous CRAB colonization. Methods: We performed an observational retrospective cohort study at ASST Sette Laghi-Varese Hospital between January 2020 and December 2022. All consecutive adult (> 18 years old) hospitalized patients with documented colonization by CRAB at any anatomical site or with CRAB infections preceded by CRAB colonization were included. Univariate and multivariate analyses were performed to investigate infection risk factors. Results: Overall, 144 patients were included in the study: 104 colonized only and 40 infected patients. Colonization and infection rates significantly changed over the years (2020–2022, p < 0.001). The incidence of infections in CRAB carriers was 27.8% (40/144). Median time from colonization to infection was 4 days (IQR 1-8.5). Overall, inhospital mortality was 32.7% and 55.0% in colonized only and infected patients, respectively. At the multivariable logistic regression cardiovascular disease (OR 5.83, 95% CI 1.12–30.43, p = 0.037), COVID-19 (OR 3.72, 95% CI 1.16–11.91, p = 0.027) and intensive care unit (ICU) admission (OR 8.83, 95% CI 2.94–26.51, p < 0.001) were risk factors independently associated with cardiovascular disease CRAB infection after colonization. Conclusions: We observed an increased infection risk in patients colonized with CRAB with cardiovascular disease, COVID-19 and admitted in ICU setting. Additional evidence is needed to identify predictors of infection in colonized patients. [ABSTRACT FROM AUTHOR]

Carbapenem-Resistant Acinetobacter baumannii (CRAB) outbreak in intensive care units (ICUs) is a significant problem for healthcare facilities. In this study, we aimed to investigate the occurrence of CRAB isolates among ICU-admitted patients during the three waves of the COVID-19 pandemic in Iran using Multiple-Locus Variable Number Tandem-Repeat Analysis (MLVA). We obtained 50 (A) baumannii isolates from tracheal aspirate and blood culture samples. In the disc diffusion method, all isolates were cefotaxime, ceftriaxone, and cefepime-resistant, while 98% (49/50) of isolates were resistant to piperacillin, piperacillin-tazobactam, ceftazidime, and ciprofloxacin. Levofloxacin and tobramycin resistance was found in 76% (38/50) of isolates. In the microbroth dilution test all isolates were resistant to imipenem, 98% (49/50) to meropenem, 68% (34/50) to colistin, and 20% (10/50) to polymyxin (B) Based on the PCR findings, all isolates harbored blaOXA−40, ISAba-1, and int-2 genes. There were no isolates found that have the blaOXA−58, blaOXA−143, blaVEB−1, blaVIM, and int-3 genes. Among Extended-spectrum beta-lactamases (ESBL) genes, blaCTX−M, blaTEM, blaSHV, blaGES, and blaPER−1 have a prevalence of 42% (21/50), 84% (42/50), 58% (29/50), 78% (39/50), and 54% (27/50), respectively. 74% (37/50) of the isolates had the blaOXA−23 gene, while all of the isolates carried the blaOXA−40 gene. Among MBL genes, blaIPM, blaGIM, blaSIM, and blaNDM−1 have a prevalence of 20% (10/50), 8% (4/50), 22% (11/50), and 60% (30/50), respectively. The prevalence of int-1 was documented as 74% (37/50). Accordingly, all isolates were identified as CRAB. The co-existence of blaOXA−23/int-2 and blaOXA−23/isaba-1 was 74% (37/50). The co-existence of blaNDM−1/ISAba-1 was observed in 30 (60%) isolates. Using an 80% similarity threshold on the dendrogram constructed through MLVA typing, all isolates were grouped into two clusters: cluster A with 9 isolates from wave 3, and cluster B with 41 isolates from waves 3, 4, and 5. Our study confirms a clonal transmission of CRAB during the study period and suggests using molecular typing methods like MLVA in healthcare settings to identify dominant clones, antibiotic resistance patterns, and transmission routes. This will help to better manage the emergence and spread of antibiotic-resistant strains in future outbreaks. [ABSTRACT FROM AUTHOR]

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

Background: We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections (BSI). Materials/methods: Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW). Results: Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%, p = 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%, p < 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (p = 0.008 and p = 0.0008, respectively). Increment of CCI (p = 0.005), ICU (p = 0.025), SARS-CoV2 (p = 0.006) and ECMO (p < 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival. Conclusions: CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided. Key summary points: Increasing real-life data support the clinical effectiveness and safety of cefiderocol (CFDC) for carbapenem resistant Acinetobacter baumannii (CRAB) infections. We investigated CFDC in comparison with colistin (COL) for the treatment of CRAB bloodstream infections (BSI). Clinical cure was higher in CFDC than COL group. Patients with hospital acquired/ventilator-associated pneumonia treated with CFDC had a statistically significant lower 30-d mortality and higher clinical cure than those treated with COL. Adverse events were more frequent in COL than in CFDC-group. CFDC could be an effective and safe treatment option for CRAB BSI, especially in patients with HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided. [ABSTRACT FROM AUTHOR]

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

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

We investigated activities of cefiderocol combination therapy against carbapenem-resistant Acinetobacter baumannii (CR-AB). A total of 123 clinical isolates of CR-AB, including 44 cefiderocol-resistant isolates were tested. Cefiderocol functioned synergistically with tigecycline in most cefiderocol-susceptible isolates (84.8%, 67/79), but not with colistin or meropenem by checkerboard method. Cefiderocol functioned synergistically with tigecycline, colistin, and meropenem in 90.9% (40/44), 47.7% (21/44), and 79.5% (35/44) cefiderocol-resistant isolates, respectively. The time-kill assay and the in vivo Galleria mellonella model confirmed these observations. In summary, cefiderocol combined with tigecycline showed synergistic effects against both cefiderocol-susceptible and -resistant CR-AB, suggesting a potentially valuable combination regimen. [ABSTRACT FROM AUTHOR]

Introduction: Antibiotic-resistant Gram-negative bacteria have been associated with substantial morbidity and mortality and have limited treatment options available. Omadacycline (OMC) is an aminomethylcycline antibiotic that has been shown to exhibit broad in vitro activity against antibiotic-resistant Gram-negative bacteria. Given the lack of real-world data, the primary objective of our report was to describe early experience with OMC for the treatment of resistant Gram-negative infections. Methods: This was a real-world, multicenter, observational cases series/pilot study conducted in the USA. Inclusion criteria included any adult patient aged ≥ 18 years who received OMC for ≥ 72 h either in the inpatient and/or outpatient setting. Clinical success was defined as a composite of 90-day survival from initiation of OMC, lack of alteration in treatment/addition of other antibiotic due to concerns of OMC failure, and lack of microbiologic recurrence within 30 days from the end of therapy. Results: Oral OMC was used in nine cases primarily for multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacterial infections (55.6% XDR and/or carbapenem-resistant Acinetobacter baumannii [CRAB]). The majority of infections were of bone/joint (55.6%) origin, followed by intra-abdominal (33.3%) origin. Clinical success occurred in 66.7% of cases, with 80.0% success each in infections of bone/joint origin or those caused by CRAB. One patient experienced an adverse effect that was not treatment limiting while on therapy (gastrointestinal). Conclusion: The use of oral OMC in MDR/XDR Gram-negative infections exhibited a relatively high success rate with minimal adverse effects. Real-world studies with larger case numbers are needed to confirm our initial findings. [ABSTRACT FROM AUTHOR]

Tigecycline is an alternative antibiotic for managing carbapenem-resistant Gram-negative bacterial infections. However, disk diffusion and automated testing often show false-intermediate or false-resistant results in tigecycline susceptibility, misleading clinical antimicrobial therapy. Broth microdilution (BMD) is the reference method for testing tigecycline susceptibility, but it is labor intensive and time consuming to perform in clinical laboratories. Therefore, a simple and accurate method is urgently needed. We evaluated the performance of VITEK 2, E-test, Kirby–Bauer disk diffusion (KB), and modified KB disk diffusion (mKB) versus BMD in testing tigecycline susceptibility of 372 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP) and 346 strains of carbapenem-resistant Acinetobacter baumannii (CRAB). BMD confirmed that 96.8% of CRKP and 91% of CRAB strains were susceptible to tigecycline. E-test, VITEK 2, KB, and mKB yielded categorical agreement of 96.7/59.3%, 69.9/54.3%, 78.5/87.3%, and 96.5%/91% for CRKP/CRAB, respectively. No very major error was found for either CRKP or CRAB by any method. No major error was found for CRKP or CRAB by the mKB method. The mKB method enhanced by R-buffer is simple, accurate, and inexpensive for clinical laboratories to test the susceptibility of CRKP and CRAB isolates to tigecycline. [ABSTRACT FROM AUTHOR]

Purpose: Acinetobacter baumannii is a non-fermenting aerobic gram-negative bacteria and one of the important nosocomial pathogens, especially in intensive care units (ICUs). In recent years, multidrug-resistant (MDR) isolates have been an emerging problem, with limited therapeutic options. Tigecycline is a novel antimicrobial, with its in vitro activity against most gram-positive and gram-negative pathogens. Methods: This is a retrospective study that was conducted in a tertiary care hospital with 550 beds in Ankara, Turkey, from January 2009 to July 2010. Thirty-three patients who had carbapenem-resistant Acinetobacter spp. infections and received tigecycline alone or in combination with other antibiotics for at least 3 days were included. Results: The median age of the patients was 62 (18-87) years. All of the patients were diagnosed and treated in the ICU. Clinical responses were observed in 23 patients (69.7%). Ten patients (30%) had clinical failure. There was no significant difference between ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in terms of clinical or microbiological outcome ( p > 0.05). The microbiological response rate was 50%. Superinfection was detected in 13 patients (43.3%) and Pseudomonas aeruginosa was the most frequently isolated pathogen. The 30-day overall mortality rate and attributable mortality rates were 57.6 and 24.2%, respectively. The attributable mortality rate was higher in the group in which microbiological eradication was not provided. Conclusions: Although it is approved by the Food and Drug Administration (FDA) for the treatment of complicated intra-abdominal infections, complicated skin and soft tissue infections, and community-acquired bacterial pneumonia, emerged resistance of Acinetobacter spp. and limited therapeutic options left physicians no choice but to use tigecycline for off-label indications. [ABSTRACT FROM AUTHOR]