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Background: The extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause of nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges of antibiotic resistance. Methods: This study investigates the biofilm formation ability of 30 XDR A. baumannii isolates and the efficacy of a cocktail of four tempetate bacteriophages (SA1, Eve, Ftm, and Gln) and different antibiotics (ampicillin/sulbactam, meropenem, and colistin) in inhibiting and degrading the biofilms of these strains. Results: The majority (83.3%) of the strains exhibited strong biofilm formation. The bacteriophage cocktail showed varying degrees of effectiveness against A. baumannii biofilms, with higher concentrations generally leading to more significant inhibition and degradation rates. The antibiotics-bacteriophage cocktail combinations also enhanced the inhibition and degradation of biofilms. Conclusion: The findings suggested that the bacteriophage cocktail is an effective tool in combating A. baumannii biofilms, with its efficacy depending on the concentration. Combining antibiotics with the bacteriophage cocktail improved the inhibition and removal of biofilms, indicating a promising strategy for managing A. baumannii infections. These results contribute to our understanding of biofilm dynamics and the potential of bacteriophage cocktails as a novel therapeutic approach to combat antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Background Studying long-term treatment outcomes of TB is time-consuming and impractical. Early and reliable biomarkers reflecting treatment response and capable of predicting long-term outcomes are urgently needed. Objectives To develop a pharmacometric multistate model to evaluate the link between potential predictors and long-term outcomes. Methods Data were obtained from two Phase II clinical trials (TMC207-C208 and TMC207-C209) with bedaquiline on top of a multidrug background regimen. Patients were typically followed throughout a 24 week investigational treatment period plus a 96 week follow-up period. A five-state multistate model (active TB, converted, recurrent TB, dropout, and death) was developed to describe observed transitions. Evaluated predictors included patient characteristics, baseline TB disease severity and on-treatment biomarkers. Results A fast bacterial clearance in the first 2 weeks and low TB bacterial burden at baseline increased probability to achieve conversion, whereas patients with XDR-TB were less likely to reach conversion. Higher estimated mycobacterial load at the end of 24 week treatment increased the probability of recurrence. At 120 weeks, the model predicted 55% (95% prediction interval, 50%–60%), 6.5% (4.2%–9.0%) and 7.5% (5.2%–10%) of patients in converted, recurrent TB and death states, respectively. Simulations predicted a substantial increase of recurrence after 24 weeks in patients with slow bacterial clearance regardless of baseline bacterial burden. Conclusions The developed multistate model successfully described TB treatment outcomes. The multistate modelling framework enables prediction of several outcomes simultaneously, and allows mechanistically sound investigation of novel promising predictors. This may help support future biomarker evaluation, clinical trial design and analysis. [ABSTRACT FROM AUTHOR]

Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study. Methods: NZW rabbit corneas with intact epithelium were inoculated with XDRPA. After 16 h, the rabbits were topically treated with cefiderocol 50 mg/mL, ciprofloxacin 0.3%, tobramycin 14 mg/mL, or saline. Following 8 h of treatment, the corneas were harvested for CFU determinations and cefiderocol concentrations. Results: Only cefiderocol significantly decreased CFU of the XDRPA strain compared with saline. The CFU in the cefiderocol and tobramycin-treated corneas for the XDRPA strain with initially intact epithelium were 1.83–1.4 Log10 greater than those produced in corneas with the abraded epithelium (p < 0.05). Cefiderocol concentrations were 5.02× less in corneas with initially intact epithelium. Conclusions: The efficacy of cefiderocol and tobramycin to treat experimental XDRPA keratitis is dependent on the state of the corneal epithelium. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effectiveness and safety of using tigecycline as a salvage therapy in critically ill children who did not respond to other antibiotics. Methods We conducted a retrospective cohort analysis that included children who received tigecycline for at least 48 hours and four doses during their pediatric intensive care unit admission. Demographic and clinical features of the subjects were evaluated through a comprehensive review of medical records. The effectiveness of tigecycline was assessed by thoroughly evaluating clinical and microbiological outcomes. Results During the study period, 72 pediatric patients with 88 episodes of infection received tigecycline according to antimicrobial susceptibility in 62.5% of cases and empirically in 37.5%. The median duration of tigecycline therapy was 10 days (range, 2–33 days). Klebsiella pneumoniae (n = 17, 30.9%) was the most frequently isolated pathogen, followed by Acinetobacter baumannii (n = 10, 18.1%). Ventilator-associated pneumonia was the most common infection (n = 29). Of the 55 isolated pathogens, 43 were multidrug-resistant (MDR), and 2 were extensively drug-resistant (XDR) gram-negative bacteria. Clinical response and microbiological clearance were achieved in 42 and 50.9% of episodes, respectively. The overall mortality was 40.9%, with an attributable mortality rate of 29.5%. Conclusion Tigecycline could be used as a salvage therapy for critically ill pediatric patients infected with MDR or XDR pathogens in the lack of alternative treatment options. [ABSTRACT FROM AUTHOR]

Abstract Background The extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause of nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges of antibiotic resistance. Methods This study investigates the biofilm formation ability of 30 XDR A. baumannii isolates and the efficacy of a cocktail of four tempetate bacteriophages (SA1, Eve, Ftm, and Gln) and different antibiotics (ampicillin/sulbactam, meropenem, and colistin) in inhibiting and degrading the biofilms of these strains. Results The majority (83.3%) of the strains exhibited strong biofilm formation. The bacteriophage cocktail showed varying degrees of effectiveness against A. baumannii biofilms, with higher concentrations generally leading to more significant inhibition and degradation rates. The antibiotics-bacteriophage cocktail combinations also enhanced the inhibition and degradation of biofilms. Conclusion The findings suggested that the bacteriophage cocktail is an effective tool in combating A. baumannii biofilms, with its efficacy depending on the concentration. Combining antibiotics with the bacteriophage cocktail improved the inhibition and removal of biofilms, indicating a promising strategy for managing A. baumannii infections. These results contribute to our understanding of biofilm dynamics and the potential of bacteriophage cocktails as a novel therapeutic approach to combat antibiotic-resistant bacteria.

Background: Salmonella enterica serotype Typhi (S. typhi) is responsible for causing Typhoid fever which is estimated to cause tens of millions of cases worldwide. Pakistan is currently experiencing an outbreak of extensively drug-resistant (XDR) typhoid. Objective: To document the frequency and clinical features of XDR typhoid and determine the utility of our treatment approach with ceftriaxone in the face of expanding resistance to this drug and document sensitivity patterns of S. typhi against other antibiotics. Methods: This retrospective cross-sectional study was conducted at the Paediatric ward and Intensive Care Unit of Liaquat National Hospital for 1 year (September 2021 to August 2022). Children aged 1 to 12 years who were diagnosed with typhoid fever were included in the study. Infants (below 1 year), suspected cases of typhoid fever without positive cultures, and cases of typhoid fever presenting in the outpatient department were excluded. SPSS v26 was used for data analysis. An independent t-test was applied for mean comparison while a chi-square/fisher-exact test was applied to check the association. P≤0.05 was considered as significant in all cases. Results: 86 cases of typhoid fever were included in the study. Mean age of the cohort was 6.012 (±3.068) years, having 15 (17.4%) MDR typhoid and 71 (82.6%) XDR cases. Fever was a common feature in all patients. Leukopenia was observed in 25.6% of cases. None of the cases showed sensitivity to ciprofloxacin. All 71 XDR cases were sensitive to meropenem and azithromycin. A significant difference was observed in terms of loose motions (p=0.005), cough (p=0.01) and seizures (p=0.03) between both groups. Conclusion: As resistance against commonly used antibiotics is emerging; organisms may show susceptibility to less commonly used first-line drugs. Ceftriaxone no longer appears to be an effective drug in the majority of cases of typhoid fever, by increase in extensively drug-resistant typhoid. Carbapenems and azithromycin are better choices for these patients; however, these should be used judiciously in an evidence-based manner.

Abstract Background The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. Results Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum β-lactamases (ESBLs) and metallo β-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6ʹ)-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. Conclusion The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.

Background: The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. Results: Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum β-lactamases (ESBLs) and metallo β-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6ʹ)-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. Conclusion: The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential. [ABSTRACT FROM AUTHOR]

Background: Due to its rapid resistance development and ability to form biofilms, treatment of Pseudomonas aeruginosa infections is becoming more complicated by the day. Drug combinations may help reduce both resistance and biofilm formation. Methods: Using the microtiter plate assay, we investigated the in vitro inhibition of biofilm formation and the disruption of preformed biofilms in multidrug-resistant and extensively drug-resistant clinical isolates of P. aeruginosa in the presence of peak plasma levels of eight antipseudomonal antibiotics alone and in combination with fosfomycin: ceftazidime, piperacillin/tazobactam, cefepime, imipenem, gentamicin, amikacin, ciprofloxacin and colistin. Results: Combination therapy was significantly superior to monotherapy in its inhibition of biofilm formation. The highest inhibition rates were observed for combinations with colistin, cefepime and ceftazidime. Conclusion: Our results support fosfomycin combination therapy as an enhanced prophylactic option. Moreover, combinations with β-lactam antibiotics and colistin demonstrated a more potent inhibition effect on biofilm formation than protein synthesis inhibitors. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis, an inflammatory rheumatic disease predominantly affecting small limb joints, frequently compromises the cervical spine, resulting in spinal instability and the potential surgical necessity. This may result in severe complications, such as ventriculitis, often associated with a high mortality rate and multidrug-resistant organisms. A major challenge lies in achieving therapeutic antimicrobial concentrations in the central nervous system.

We whole-genome sequence a drug-resistant Pseudomonas aeruginosa strain (PANU108) isolated in 2020 from an elderly male patient admitted to an intensive care unit with bloodstream infection in Khartoum, Sudan. The analysis of the sequenced data revealed that the strain is sequence type 319 (ST319) and carrying 11 acquired resistance genes belonging to 5 drug classes. Interestingly, we found that PANU108 strain harbouring blaTMB-1 resistance gene. To the best of our knowledge, this the first report of a P. aeruginosa producing Tripoli Metallo-β-lactamase 1 (TMB-1) resistance determinant.

ABSTRACT: Salmonella, which is widely distributed in nature, is an important zoonotic pathogen affecting humans, livestock, and other animals. Salmonella infection not only hinders the development of livestock and poultry-related industries but also poses a great threat to human health. In this study, we collected 1,537 samples including weak chicks, dead embryos, fecal samples and environmental samples from 2020 to 2023 (for a period of 1 to 2 months per year) to keep a long-term monitor the prevalence of Salmonella in an intensive laying hen farm, 105 Salmonella strains were isolated with an isolation rate of 6.83% (105/1,537). It revealed a significant decrease in prevalence rates of Salmonella over time (P < 0.001). Before 2020, the predominant serotype was S. Enteritidis. S. Kentucky was first detected in November 2020 and its proportion was gradually found to exceed that of S. Enteritidis since then. S. Kentucky isolates were distributed in various links of the four regions in the poultry farm. A total of 55 S. Kentucky strains, were assigned to ST198 based on whole genome sequencing. Among them, 54 strains were resistant to 12 to 16 antibiotics, indicating that they were extensively drug-resistant (XDR). Seventeen antimicrobial resistance genes were detected in 55 S. Kentucky isolates. For most of these isolates, antibiotic resistance phenotypes were concordant with their genotypes. All S. Kentucky strains isolated from this farm in 2020 to 2023 showed a high similarity based on their core-genome SNP-based phylogeny. The traceability analysis revealed that S. Kentucky was introduced to the farm through newly purchased flocks. The long-term existence of XDR S. Kentucky ST198 poses a substantial risk because of the multiage management and circulation of workers in this poultry farm. Thus, this study is the first to report extensively drug-resistant S. Kentucky ST198 detected in this intensive poultry farm in China.

Tuberculosis has remained the principal cause of mortality worldwide, and one of the major sources of concern is drug-resistant TB. The increasing emergence of extensively drug-resistant and multidrug-resistant TB has further increased the TB epidemic. In this current work, we suggest a model to study the transmission of TB with extensively drug-resistant and multidrug-resistant compartments, incorporating chemoprophylaxis treatment. In the theoretical analysis, the concept of the next-generation matrix and the Jacobian method are applied to obtain a formula that states the reproductive number. The existence of endemic and disease-free equilibrium points was checked, and their stability has been analyzed using the Lyapunov method. The qualitative-based analysis indicated the local asymptotic stability of the disease-free-state for R0 1, whereas the endemic state is globally asymptotically stable if R0 1. Moreover, sensitivity analysis was carefully done using normalized forward sensitivity, and numerical simulation was carried out. Based on the results of numerical simulation and sensitivity analysis, chemoprophylaxis treatment was found to drastically minimize the progression of exposed individuals to infectious classes and also reduce the progression to extensively drug-resistant and multidrug-resistant classes, which decreases disease transmission.

The occurrence of multidrug-resistant Acinetobacter baumannii (MDRA) has increased rapidly and is associated with severe nosocomial infections. MDRA has emerged in the hospital setting and has evolved into extensively drug-resistant A. baumannii (XDRA). A clinical XDRA isolate obtained from a hospitalised patient in 2016 was evaluated for antibiotic susceptibility and whole-genome sequence. The XDRA isolate was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, and to aminoglycosides, fosfomycin, fluoroquinolones, tetracyclines, tigecycline, and trimethoprim-sulfamethoxazole. The isolate harboured abaF, ant(3″)-II-c, aph(3″)-Ib, aph(6)-Id, armA, blaADC-73, blaTEM-1, blaOXA-66, blaOXA-23, mphE, msrE and tet(B). Quinolone resistance was associated with mutations gyrA S81L and parC S84L. Tigecycline resistance was associated with a mutation in adeS. The isolate belonged to Oxford and Pasteur scheme sequence type 1050 and 2, respectively, and harboured a conjugative plasmid containing the aminoglycoside resistance transposon TnaphA6. Our study demonstrates that the isolate is closely related to a recent MDRA identified in Australia and the USA, in which a similar conjugative plasmid is not observed. Although the MDRA in Australia caused an outbreak, our hospital's surveillance protocol managed to prevent a further outbreak. Our finding suggests that this XDRA isolate is of concern in hospital and community care settings. The gpi allele could be a marker for discriminating this isolate from clonal complex 92 isolates.

Introduction: Acinetobacter spp. has emerged as an important hospital-acquired and opportunistic agent due to its survival capability in adverse conditions, saprophytic presence, and increasing resistance to antimicrobials. The irrational use of antibiotics, along with biofilm formation, plays an important role in producing Extensively Drug-resistant (XDR) and MultidrugResistant (MDR) Acinetobacter species, especially Acinetobacter calcoaceticus-baumannii complex (Acb complex), in the hospital environment, contributing to morbidity and mortality. Aim: To detect biofilm production among Acinetobacter species isolated from various clinical samples received from Intensive Care Units (ICUs) as well as their antibiotic sensitivity pattern. Materials and Methods: A cross-sectional study was conducted in the Microbiology Department at Teerthanker Mahaveer Medical College and Research Centre, Moradabad, Uttar Pradesh, India from January 2022 to April 2023. Patients of all age groups and both genders were included in the study after obtaining informed consent. Clinical specimens, including endotracheal secretions, endotracheal tips, pus, urine, sputum, tissue, and other body fluids, were collected from ICUs where Acinetobacter spp. was detected. A total of 223 cases were included. The specimens were collected using clean, leak-proof, sterile containers with proper aseptic precautions. Antimicrobial susceptibility testing was performed according to the guidelines set by the Clinical and Laboratory Standards Institute (CLSI) in 2022 and identifies MDR and XDR strains. The biofilm production of isolates was determined using a quantitative adherence assay. The data generated was entered into Microsoft excel, and statistical analysis was conducted using International Business Machines (IBM) Statistical Package for Social Sciences (SPSS) statistical software version 28.0. The results were then presented as descriptive statistics. Results: Among the 223 Acinetobacter spp. isolates, 159 (71.3%) were identified as Acb complex (Acinetobacter calcoaceticusbaumannii complex), followed by A.lwofi with 39 (17.5%) isolates and A. haemolyticus with 16 (7.2%) isolates. Acinetobacter showed resistance, in descending order of frequency, to amoxicillin+clavulanic acid (211 isolates, 94.6%), ciprofloxacin (211 isolates, 94.6%), trimethoprim-sulfamethoxazole (208 isolates, 93.3%), cefotaxime (198 isolates, 88.8%), cefepime (187 isolates, 83.8%), gentamycin (178 isolates, 79.8%), amikacin (152 isolates, 68.2%), piperacillin-tazobactam (68 isolates, 30.5%), imipenem (72 isolates, 32.3%), meropenem (71 isolates, 31.8%), polymyxin B (12 isolates, 5.4%), and colistin (2 isolates, 0.9%). The maximum antibiotic resistance was observed in Acb complex, with 208 (93.3%) strains being MDR producers and 32 (14.3%) strains being XDR producers. Biofilm production was observed in 214 isolates (95.9%), with 127 (56.9%) exhibiting strong biofilm production 63 (28.2%) showing moderate biofilm production, and 24 (10.8%) showing weak biofilm production. All MDR strains were found to produce biofilm, and out of those, 127 (61.1%) exhibited strong biofilm production. Among the XDR strains, all 32 (100%) were found to produce strong biofilm. Conclusion: In conclusion, Acinetobacter spp. has a high propensity for developing MDR, and the formation of biofilms further aids the organism in surviving under strenuous conditions, making it difficult to treat. Therefore, regular surveillance of Hospital-acquired Infections (HAI), the prevention of misuse and overuse of antibiotics, prescribing antibiotics based on antibiogram patterns, formulating antibiotic policies, and implementing bundle care approaches for the prevention of HAI are crucial in preventing antibiotic resistance.

Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study. Methods: NZW rabbit corneas with intact epithelium were inoculated with XDRPA. After 16 h, the rabbits were topically treated with cefiderocol 50 mg/mL, ciprofloxacin 0.3%, tobramycin 14 mg/mL, or saline. Following 8 h of treatment, the corneas were harvested for CFU determinations and cefiderocol concentrations. Results: Only cefiderocol significantly decreased CFU of the XDRPA strain compared with saline. The CFU in the cefiderocol and tobramycin-treated corneas for the XDRPA strain with initially intact epithelium were 1.83–1.4 Log10 greater than those produced in corneas with the abraded epithelium (p < 0.05). Cefiderocol concentrations were 5.02× less in corneas with initially intact epithelium. Conclusions: The efficacy of cefiderocol and tobramycin to treat experimental XDRPA keratitis is dependent on the state of the corneal epithelium.

Introduction: Extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a growing concern due to its increasing incidence, limited therapeutic options, limited data on the optimal treatment, and high mortality rates. The study aimed to characterize the population, the outcome and the microbiological characteristics of XDR-PA identified in a Portuguese university hospital center. Methods: All XDR-PA isolates between January 2019 and December 2021 were identified. XDR-PA was defined as resistance to piperacillin-tazobactam, third and fourth generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. A retrospective analysis of the medical records was performed. Results: One hundred seventy-eight individual episodes among 130 patients with XDR-PA detection were identified. The most common sources of infection were respiratory (32%) and urinary tracts (30%), although skin and soft tissue infections (18%) and primary bacteremia (14%) were also prevalent. Colonization was admitted in 64 cases. Several patients had risk factors for complicated infections, most notably immunosuppression, structural lung abnormalities, major surgery, hemodialysis or foreign intravascular or urinary devices. XDRPA identification was more frequent in male patients with an average age of 64.3 = 17.5 years. One non-susceptibility to colistin was reported. Only 12.4% were susceptible to aztreonam. Ceftazidime-avibactam (CZA) was susceptible in 71.5% of the tested isolates. Ceftolozane-tazobactam (C/T) was susceptible in 77.5% of the tested isolates. Antibiotic regimens with XDR-PA coverage were reserved for patients with declared infection, except to cystic fibrosis. The most frequently administered antibiotics were colistin (41 cases), CZA (39 cases), and C/T (16 cases). When combination therapy was used, CZA plus colistin was preferred. The global mortality rate among infected patients was 35.1%, significantly higher in those with hematologic malignancy (50.0%, p < 0.05), followed by the ones with bacteremia (44.4%, p < 0.05) and those medicated with colistin (39.0%, p < 0.05), especially the ones with respiratory infections (60.0%). Among patients treated with CZA or C/T, the mortality rate seemed to be lower. Discussion: XDR-PA infections can be severe and difficult to treat, with a high mortality rate. Even though colistin seems to be a viable option, it is likely less safe and efficient than CZA and C/T. To the best of the authors' knowledge, this is the first description of the clinical infection characteristics and treatment of XDR-PA in Portugal. [ABSTRACT FROM AUTHOR]

The occurrence of multidrug-resistant Acinetobacter baumannii (MDRA) has increased rapidly and is associated with severe nosocomial infections. MDRA has emerged in the hospital setting and has evolved into extensively drug-resistant A. baumannii (XDRA). A clinical XDRA isolate obtained from a hospitalised patient in 2016 was evaluated for antibiotic susceptibility and whole-genome sequence. The XDRA isolate was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, and to aminoglycosides, fosfomycin, fluoroquinolones, tetracyclines, tigecycline, and trimethoprim-sulfamethoxazole. The isolate harboured abaF , ant(3″)-II-c , aph(3″)-Ib , aph(6)-Id , armA , bla ADC-73 , bla TEM-1 , bla OXA-66 , bla OXA-23 , mphE , msrE and tet(B). Quinolone resistance was associated with mutations gyrA S81L and parC S84L. Tigecycline resistance was associated with a mutation in adeS. The isolate belonged to Oxford and Pasteur scheme sequence type 1050 and 2, respectively, and harboured a conjugative plasmid containing the aminoglycoside resistance transposon Tn aphA6. Our study demonstrates that the isolate is closely related to a recent MDRA identified in Australia and the USA, in which a similar conjugative plasmid is not observed. Although the MDRA in Australia caused an outbreak, our hospital's surveillance protocol managed to prevent a further outbreak. Our finding suggests that this XDRA isolate is of concern in hospital and community care settings. The gpi allele could be a marker for discriminating this isolate from clonal complex 92 isolates. [ABSTRACT FROM AUTHOR]

Background: Proteus mirabilis (P. mirabilis) is known to cause various infections, most commonly urinary tract infections, and is a threat to hospitalized patients, especially in long-stay departments that utilize invasive devices. This study aims to fill the knowledge gap regarding P. mirabilis epidemiology and antimicrobial resistance in Saudi Arabia. It investigates epidemiological patterns, resistance characteristics, and clinical outcomes among P. mirabilis patients at King Fahad Medical City in Riyadh from 2019 to 2021. Methods: A total of 598 P. mirabilis isolated from diverse clinical specimens, including the clinical information of 78 intensive care unit (ICU) patients, were included in the current study. The Phoenix BD instrument was used for complete identification and sensitivity testing of Proteus spp. Demographic, clinical, and outcome data were reported and compared using statistical analysis. Results: Pan-drug-resistant isolates were identified in 2019 (n = 6), although multi- and extensively drug-resistant isolate frequencies were greatest among all patients in 2019. The highest susceptibility levels were observed for piperacillin-tazobactam, carbapenems, and cephalosporins antibiotics. In contrast, Cephalothin, trimethoprim-sulfamethoxazole, and ampicillin had the lowest susceptibilities. Urine infections with a positive culture of P. mirabilis were significantly higher in females and non-ICU patients (p < 0.001), but respiratory infections were significantly higher in ICU patients (p < 0.001). Moreover, ICU patients infected with P. mirabilis and undergoing renal dialysis have a 7.2-fold (P 0.034) higher risk of death than those not receiving dialysis. Conclusion: Hospitalized patients are at risk of fatal consequences due to P. mirabilis infection. It is crucial to conduct further investigation to fully understand the severity of this issue and take necessary measures to prevent it. [ABSTRACT FROM AUTHOR]

Introduction: Acinetobacter spp. has emerged as an important hospital-acquired and opportunistic agent due to its survival capability in adverse conditions, saprophytic presence, and increasing resistance to antimicrobials. The irrational use of antibiotics, along with biofilm formation, plays an important role in producing Extensively Drug-resistant (XDR) and Multidrug-Resistant (MDR) Acinetobacter species, especially Acinetobacter calcoaceticus-baumannii complex (Acb complex), in the hospital environment, contributing to morbidity and mortality. Aim: To detect biofilm production among Acinetobacter species isolated from various clinical samples received from Intensive Care Units (ICUs) as well as their antibiotic sensitivity pattern. Materials and Methods: A cross-sectional study was conducted in the Microbiology Department at Teerthanker Mahaveer Medical College and Research Centre, Moradabad, Uttar Pradesh, India from January 2022 to April 2023. Patients of all age groups and both genders were included in the study after obtaining informed consent. Clinical specimens, including endotracheal secretions, endotracheal tips, pus, urine, sputum, tissue, and other body fluids, were collected from ICUs where Acinetobacter spp. was detected. A total of 223 cases were included. The specimens were collected using clean, leak-proof, sterile containers with proper aseptic precautions. Antimicrobial susceptibility testing was performed according to the guidelines set by the Clinical and Laboratory Standards Institute (CLSI) in 2022 and identifies MDR and XDR strains. The biofilm production of isolates was determined using a quantitative adherence assay. The data generated was entered into Microsoft excel, and statistical analysis was conducted using International Business Machines (IBM) Statistical Package for Social Sciences (SPSS) statistical software version 28.0. The results were then presented as descriptive statistics. Results: Among the 223 Acinetobacter spp. isolates, 159 (71.3%) were identified as Acb complex (Acinetobacter calcoaceticus-baumannii complex), followed by A. lwofi with 39 (17.5%) isolates and A. haemolyticus with 16 (7.2%) isolates. Acinetobacter showed resistance, in descending order of frequency, to amoxicillin+clavulanic acid (211 isolates, 94.6%), ciprofloxacin (211 isolates, 94.6%), trimethoprim-sulfamethoxazole (208 isolates, 93.3%), cefotaxime (198 isolates, 88.8%), cefepime (187 isolates, 83.8%), gentamycin (178 isolates, 79.8%), amikacin (152 isolates, 68.2%), piperacillin-tazobactam (68 isolates, 30.5%), imipenem (72 isolates, 32.3%), meropenem (71 isolates, 31.8%), polymyxin B (12 isolates, 5.4%), and colistin (2 isolates, 0.9%). The maximum antibiotic resistance was observed in Acb complex, with 208 (93.3%) strains being MDR producers and 32 (14.3%) strains being XDR producers. Biofilm production was observed in 214 isolates (95.9%), with 127 (56.9%) exhibiting strong biofilm production 63 (28.2%) showing moderate biofilm production, and 24 (10.8%) showing weak biofilm production. All MDR strains were found to produce biofilm, and out of those, 127 (61.1%) exhibited strong biofilm production. Among the XDR strains, all 32 (100%) were found to produce strong biofilm. Conclusion: In conclusion, Acinetobacter spp. has a high propensity for developing MDR, and the formation of biofilms further aids the organism in surviving under strenuous conditions, making it difficult to treat. Therefore, regular surveillance of Hospital-acquired Infections (HAI), the prevention of misuse and overuse of antibiotics, prescribing antibiotics based on antibiogram patterns, formulating antibiotic policies, and implementing bundle care approaches for the prevention of HAI are crucial in preventing antibiotic resistance. [ABSTRACT FROM AUTHOR]

ABSTRACTGram-negative metallo-β-lactamase-producing bacteria can be extremely problematic, especially when found to be extensively drug-resistant (XDR). Cefiderocol is a novel antimicrobial that has been shown to overcome most carbapenemases, with very rare resistance reported to date. Within our institution, two multidrug-resistant and one XDR strains were isolated from a patient who recently emigrated from India. Each isolate underwent whole-genome sequencing to resolve plasmids and determine phylogenetics, strain typing, and mechanisms of resistance. The XDR E. coli was ST167, harbored NDM-5, cirA and PBP3 mutations, consistent with cefiderocol resistance. Our study suggests that the NDM region is required in conjunction with cirA and PBP3 mutations. It is not clear why; however, our study did determine a potential novel iron-transport region unique to the cefiderocol-resistant isolate. This is the first characterized cefiderocol-resistant E.coli reported from Canada. Health centers should be on alert for this clone.IMPORTANCEThe development of cefiderocol, a novel siderophore cephalosporin, has provided additional options to the treatment of extensively drug-resistant (XDR) Gram-negative bacteria. Resistance to cefiderocol is poorly understood and only recently described. Here, we describe a case of a patient with recent travel to India harboring three Escherichia coli isolates, one resistant and two susceptible to cefiderocol. Two isolates are highly similar genetically, allowing the mechanism of resistance to be described more closely. The importance of this manuscript contributes both globally to the understanding of cefiderocol resistance in E. coli as well as nationally as this is the first resistant case reported in Canada. This is especially concerning as cefiderocol is not currently approved in Canada. The implications of reporting emerging resistance to new antimicrobials for XDR Gram negatives are impactful to infectious disease specialists, clinical microbiologists, physicians, and public health.

Abstract In nature, terpene nucleosides are relatively rare, with 1-tuberculosinyladenosine (1-TbAd) being an exclusive feature of Mycobacterium tuberculosis (Mtb). The convergence of nucleosides and terpene pathways in the Mtb complex appears to have emerged late in its evolutionary history. 1-TbAd (PDB ID: 3WQK) is a prominent chemical marker for Mtb and may contribute to its virulence-related properties when exported extracellularly. We gathered a comprehensive set of 270 phytochemicals from diverse Ayurvedic texts and treatment traditions. Subsequently, we conducted structure-based molecular docking analyses to identify compounds exhibiting the strongest binding affinity for 1-TbAd, highlighting their potential as drug candidates. These selected compounds were further subjected to an in-vitro growth inhibition assay against the reference strain Mycobacterium tuberculosis h37rv. Among the candidates, Asiaticoside A (ASA) emerged as a promising candidate from the pool of 270 compounds. To assess the impact of ASA on 1-TbAd expression, we employed a PCR-based mRNA expression assay, revealing ASA's ability to downregulate 1-TbAd expression in extensively drug-resistant MTb strains. Remarkably, the conventional drug rifampin showed no such effectiveness in our experiments. We further conducted molecular dynamic simulations to explore the interaction between ASA and 1-TbAd in a cellular-like environment, confirming the stability of their interaction. Also, we predicted ASA's stability toward causing inducing the random mutations in the target gene. With this, we propose a novel target and its modulator to treat extensively drug-resistant MTB. Graphical Abstract

Background: Due to its rapid resistance development and ability to form biofilms, treatment of Pseudomonas aeruginosa infections is becoming more complicated by the day. Drug combinations may help reduce both resistance and biofilm formation. Methods: Using the microtiter plate assay, we investigated the in vitro inhibition of biofilm formation and the disruption of preformed biofilms in multidrug-resistant and extensively drug-resistant clinical isolates of P. aeruginosa in the presence of peak plasma levels of eight antipseudomonal antibiotics alone and in combination with fosfomycin: ceftazidime, piperacillin/tazobactam, cefepime, imipenem, gentamicin, amikacin, ciprofloxacin and colistin. Results: Combination therapy was significantly superior to monotherapy in its inhibition of biofilm formation. The highest inhibition rates were observed for combinations with colistin, cefepime and ceftazidime. Conclusion: Our results support fosfomycin combination therapy as an enhanced prophylactic option. Moreover, combinations with β-lactam antibiotics and colistin demonstrated a more potent inhibition effect on biofilm formation than protein synthesis inhibitors.

Abstract Introduction Healthcare-associated infections (HAI) and bacterial antimicrobial resistance posed a therapeutic risk during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to analyze the HAIs in COVID-19 patients in the Intensive Care Unit (ICU) and non-ICU at the University Hospital in Krakow (UHK) with an emphasis on the susceptibility of the most frequently isolated pathogens and the prevalence of extensively drug resistant (XDR) microorganisms. Methods This laboratory-based study was carried out at the University Hospital in Krakow in the ICU and non-ICUs dedicated to COVID-19 patients between May 2021 and January 2022. All isolates of Klebsiella pneumoniae were analyzed using PFGE protocol. Results 292 independent HAI cases were identified, with the predominance of urinary tract infections (UTI), especially in the non-ICU setting. The most common ICU syndrome was pneumonia (PNA). The prevalence of XDR organisms was 22.6% in the ICU and 14.8% in non-ICUs among all isolates. The incidence of carbapenem-resistant Enterobacteriaceae infection was 24.8 cases per 10,000 hospitalizations and the carbapenem-resistant A. baumannii infection incidence was 208.8 cases per 10,000 hospitalizations. The prevalence of XDR strains was highest in Acinetobacter spp, in PNA cases. The PFGE typing demonstrated that almost all XDR strains varied widely from each other. Conclusions In this study, there was a high incidence of HAI in COVID-19 patients, especially when compared to Western Europe and the United States. Similarly, the prevalence of XDR microorganisms, especially XDR-A.baumannii, was also high. PFGE did not confirm the horizontal spread of any organism strains.

IntroductionExtensively drug-resistant Pseudomonas aeruginosa (XDR-PA) is a growing concern due to its increasing incidence, limited therapeutic options, limited data on the optimal treatment, and high mortality rates. The study aimed to characterize the population, the outcome and the microbiological characteristics of XDR-PA identified in a Portuguese university hospital center.MethodsAll XDR-PA isolates between January 2019 and December 2021 were identified. XDR-PA was defined as resistance to piperacillin-tazobactam, third and fourth generation cephalosporins, carbapenems, aminoglycosides and fluoroquinolones. A retrospective analysis of the medical records was performed.ResultsOne hundred seventy-eight individual episodes among 130 patients with XDR-PA detection were identified. The most common sources of infection were respiratory (32%) and urinary tracts (30%), although skin and soft tissue infections (18%) and primary bacteremia (14%) were also prevalent. Colonization was admitted in 64 cases. Several patients had risk factors for complicated infections, most notably immunosuppression, structural lung abnormalities, major surgery, hemodialysis or foreign intravascular or urinary devices. XDR-PA identification was more frequent in male patients with an average age of 64.3 ± 17.5 years. One non-susceptibility to colistin was reported. Only 12.4% were susceptible to aztreonam. Ceftazidime-avibactam (CZA) was susceptible in 71.5% of the tested isolates. Ceftolozane-tazobactam (C/T) was susceptible in 77.5% of the tested isolates. Antibiotic regimens with XDR-PA coverage were reserved for patients with declared infection, except to cystic fibrosis. The most frequently administered antibiotics were colistin (41 cases), CZA (39 cases), and C/T (16 cases). When combination therapy was used, CZA plus colistin was preferred. The global mortality rate among infected patients was 35.1%, significantly higher in those with hematologic malignancy (50.0%, p < 0.05), followed by the ones with bacteremia (44.4%, p < 0.05) and those medicated with colistin (39.0%, p < 0.05), especially the ones with respiratory infections (60.0%). Among patients treated with CZA or C/T, the mortality rate seemed to be lower.DiscussionXDR-PA infections can be severe and difficult to treat, with a high mortality rate. Even though colistin seems to be a viable option, it is likely less safe and efficient than CZA and C/T. To the best of the authors’ knowledge, this is the first description of the clinical infection characteristics and treatment of XDR-PA in Portugal.

Purpose: To report a case of bacterial keratitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain linked to contaminated artificial tears in the United States. The ulcer was successfully treated without perforation or extracorneal spread. Observations: An 81-year-old patient presented with a corneal ulcer of the right eye. The patient had a notable complex ocular history including glaucoma and corneal edema from corneal decompensation after prolonged retained lens fragment. Despite starting hourly fortified tobramycin and vancomycin eye drops, the infiltrate grew significantly by the next day. Bacterial culture grew Pseudomonas aeruginosa that was resistant to all tested antibiotics except for intermediate susceptibility to colistin and susceptibility to cefiderocol. Tobramycin-soaked collagen shields were applied daily for three days, and the patient was started on fortified colistin eye drops. The ulcer improved and, after seven weeks of therapy, the infiltrate resolved and resulted in a large central corneal scar. Conclusions and Importance: A combination of fortified colistin and tobramycin (administered via a combination of fortified eye drops and tobramycin-soaked collagen shields) appears to be an effective treatment option for extensively drug-resistant Pseudomonas aeruginosa corneal ulcers.

In nature, terpene nucleosides are relatively rare, with 1-tuberculosinyladenosine (1-TbAd) being an exclusive feature of Mycobacterium tuberculosis (Mtb). The convergence of nucleosides and terpene pathways in the Mtb complex appears to have emerged late in its evolutionary history. 1-TbAd (PDB ID: 3WQK) is a prominent chemical marker for Mtb and may contribute to its virulence-related properties when exported extracellularly. We gathered a comprehensive set of 270 phytochemicals from diverse Ayurvedic texts and treatment traditions. Subsequently, we conducted structure-based molecular docking analyses to identify compounds exhibiting the strongest binding affinity for 1-TbAd, highlighting their potential as drug candidates. These selected compounds were further subjected to an in-vitro growth inhibition assay against the reference strain Mycobacterium tuberculosis h37rv. Among the candidates, Asiaticoside A (ASA) emerged as a promising candidate from the pool of 270 compounds. To assess the impact of ASA on 1-TbAd expression, we employed a PCR-based mRNA expression assay, revealing ASA's ability to downregulate 1-TbAd expression in extensively drug-resistant MTb strains. Remarkably, the conventional drug rifampin showed no such effectiveness in our experiments. We further conducted molecular dynamic simulations to explore the interaction between ASA and 1-TbAd in a cellular-like environment, confirming the stability of their interaction. Also, we predicted ASA's stability toward causing inducing the random mutations in the target gene. With this, we propose a novel target and its modulator to treat extensively drug-resistant MTB. Key points: In-silico screening studies for identifying the hit compound mRNA expression analysis for validation of hit compound Random in-silico mutagenesis and Molecular dynamic simulation studies for evaluating the efficiency of Asiaticoside A. [ABSTRACT FROM AUTHOR]

Introduction: Healthcare-associated infections (HAI) and bacterial antimicrobial resistance posed a therapeutic risk during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to analyze the HAIs in COVID-19 patients in the Intensive Care Unit (ICU) and non-ICU at the University Hospital in Krakow (UHK) with an emphasis on the susceptibility of the most frequently isolated pathogens and the prevalence of extensively drug resistant (XDR) microorganisms. Methods: This laboratory-based study was carried out at the University Hospital in Krakow in the ICU and non-ICUs dedicated to COVID-19 patients between May 2021 and January 2022. All isolates of Klebsiella pneumoniae were analyzed using PFGE protocol. Results: 292 independent HAI cases were identified, with the predominance of urinary tract infections (UTI), especially in the non-ICU setting. The most common ICU syndrome was pneumonia (PNA). The prevalence of XDR organisms was 22.6% in the ICU and 14.8% in non-ICUs among all isolates. The incidence of carbapenem-resistant Enterobacteriaceae infection was 24.8 cases per 10,000 hospitalizations and the carbapenem-resistant A. baumannii infection incidence was 208.8 cases per 10,000 hospitalizations. The prevalence of XDR strains was highest in Acinetobacter spp, in PNA cases. The PFGE typing demonstrated that almost all XDR strains varied widely from each other. Conclusions: In this study, there was a high incidence of HAI in COVID-19 patients, especially when compared to Western Europe and the United States. Similarly, the prevalence of XDR microorganisms, especially XDR-A.baumannii, was also high. PFGE did not confirm the horizontal spread of any organism strains. [ABSTRACT FROM AUTHOR]

Extensively drug-resistant (XDR) bacteria are the main caues for causing clinical infectious diseases. Our aim was to distinguish the present molecular epidemiological situation of XDR Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli isolates recovered from local hospitals in Changzhou. Antibiotic susceptibility and phenotypic analysis, multilocus sequence typing and Pulsed Field Gel Electrophoresis were performed to trace these isolates. Resistant phenotype and gene analysis from 29 XDR strains demonstrated that they mainly included TEM, CTX-M-1/2, OXA-48, and KPC products. A. baumannii strains belonged to sequence type (ST) ST224, and carrying the blaCTX-M-2/TEM gene. The quinolone genes aac(6’)-ib-cr and qnrB were carrying only in A. baumannii and E.coli. Three (2.3%) of these strains were found to contain the blaNDM-1 or blaNDM-5 gene. A new genotype of K. pneumoniae was found as ST2639. Epidemic characteristics of the XDR clones showed that antibiotic resistance genes distributed unevenly in different wards in Changzhou’s local hospitals. With the sequencing of blaNDM carrying isolates, the plasmids often carrying a highly conservative Tn3-relavent mobile genetic element. The especially coupled insert sequence ISKox3 may be a distinctive resistance gene transfer loci. The genotypic diversity variation of XDRs suggested that tracking and isolating the sources of antibiotic resistance especially MBL-encoding genes such as blaNDM—will help manage the risk of infection by these XDRs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in progressive and symmetric muscle weakness and atrophy of the proximal limbs and trunk due to degeneration of spinal alpha-motor neurons. Children are classified into types 1--3, from severe to mild, according to the time of onset and motor ability. Children with type 1 are the most severe, are unable to sit independently, and experience a series of respiratory problems, such as hypoventilation, reduced cough, and sputum congestion. Respiratory failure is easily complicated by respiratory infections and is a major cause of death in children with SMA. Most type 1 children die within 2 years of age. Type 1 children with SMA usually require hospitalization for lower respiratory tract infections and invasive ventilator-assisted ventilation in severe cases. These children are frequently infected with drug-resistant bacteria due to repeated hospitalizations and require long hospital stays requiring invasive ventilation. In this paper, we report a case of nebulization combined with intravenous polymyxin B in a child with spinal muscular atrophy with extensively drugresistant Acinetobacter baumannii pneumonia, hoping to provide a reference for the treatment of children with extensively drug-resistant Acinetobacter baumannii pneumonia. [ABSTRACT FROM AUTHOR]

The discovery of antibiotics has revolutionized medicine and has changed medical practice, enabling successful fighting of infection. However, quickly after the start of the antibiotic era, therapeutics for infectious diseases started having limitations due to the development of antimicrobial resistance. Since the antibiotic pipeline has largely slowed down, with few new compounds being produced in the last decades and with most of them belonging to already-existing classes, the discovery of new ways to treat pathogens that are resistant to antibiotics is becoming an urgent need. To that end, bacteriophages (phages), which are already used in some countries in agriculture, aquaculture, food safety, and wastewater plant treatments, could be also used in clinical practice against bacterial pathogens. Their discovery one century ago was followed by some clinical studies that showed optimistic results that were limited, however, by some notable obstacles. However, the rise of antibiotics during the next decades left phage research in an inactive status. In the last decades, new studies on phages have shown encouraging results in animals. Hence, further studies in humans are needed to confirm their potential for effective and safe treatment in cases where there are few or no other viable therapeutic options. This study reviews the biology and applications of phages for medical and non-medical uses in a narrative manner. [ABSTRACT FROM AUTHOR]

Objective: Sepsis due to the drug resistant infections is associated with the higher mortality rates in an intensive care unit (ICU). The aim of this study was to determine the demographic characteristics of the deceased critically ill patients, prevalence of the sepsis, and extensively drug resistant infectious-related (XDR) deaths within a year in the ICU. Materials and Methods: The data of patients who died in the ICU between January 1, 2019 and 2020 was retrospectively analyzed. Results: Out of 525 patients admitted to the ICU, 269 of them died. One hundred fifty-one of those deceased patients (56.1%) were in medical and 118 (43.9%) in the surgical ICU. Their mean age was 70.5±15 years and 126 (46.8%) of them were female. The mean Acute Physiology and Chronic Health Evaluation-II, Glasgow coma score, Sequential Organ Failure Assessment scores at ICU admission were 23.4±20.9, 9.8±4.4, and 8.2±3.6, respectively. A few reasons for the ICU admission were: respiratory failure (34.9%), neurologic dysfunction (19%), sepsis (17.8%), and cardiovascular failure (16%). Infection occurred in the 231 (85.9%) patients. Of the 109 (40.5%) deceased patients with the diagnosis of sepsis, 48 (40%) of them were admitted in the ICU with sepsis. The most common site of infection was the respiratory system (34.6%). Septic shock was seen in 170 patients (63.2%) and renal replacement therapy was needed in 61 (22.7%) of them. XDR developed in 34.6% of the deceased patients and was more frequent among those with an antibiotic usage before the ICU admission (p=0.02). The mean length of stay at hospital before the ICU admission and length of the ICU stay were 22±25.8 and 10.1±12.7 days, respectively. The number of the deceased medical patients were significantly higher than the surgical patients (p=0.018). Conclusion: The deceased critically ill medical patients were higher than the surgical patients. A total of 40% of the deceased critically ill patients were diagnosed with a sepsis, and one third of them had XDR infection. XDR infections were more frequent among the patients with an antibiotic usage before the ICU admission.

Background Mycobacterium tuberculosis (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with a β-lactamase inhibitor clavulanate, was effective in MDR and XDR tuberculosis (TB). However, clavulanate can only be used in drugs containing amoxicillin in Korea. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients. Methods The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets blaC, blaI, ldtA, ldtB, dacB2, and crfA were analyzed by PCR and DNA sequencing. Results The MIC90 values of amoxicillin and meropenem with clavulanate in drug-resistant Mtb isolates were 64 and 16, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation of was found in the blaC gene related to β-lactam antibiotics high susceptibility. Conclusion Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

Aims Extensively drug-resistant (XDR) Acinetobacter baumannii poses a severe threat to public health due to its ability to form biofilms and persister cells, which contributes to critical drug resistance and refractory device-associated infections. A novel strategy to alleviate such an emergency is to identify promising compounds that restore the antimicrobial susceptibility of existing antibiotics against refractory infections. Methods and Results Here, we found a significant synergy among three combinations of SPR741, clarithromycin and erythromycin with a potent antimicrobial activity against XDR A. baumannii (SPR741/CLA/E at 8/10/10 μg ml–1 for XDR AB1069 and at 10/16/10 μg ml–1 for XDR AB1208, respectively). Moreover, the triple combination therapy exhibits a significant antipersister and antibiofilm effect against XDR strains. Mechanistic studies demonstrate that SPR741 may promote intracellular accumulation of macrolides by permeabilizing the outer membrane as well as disrupting membrane potential and further enhance the quorum sensing inhibition activity of the macrolides against XDR A. baumannii and its biofilms. In addition, the triple combination of SPR741 with clarithromycin and erythromycin was not easy to induce resistance in A. baumannii and had effective antimicrobial activity with low toxicity in vivo. Significance and Impact of the Study Collectively, these results reveal the potential of SPR741 in combination with clarithromycin and erythromycin as a clinical therapy for refractory infections caused by XDR A. baumannii. [ABSTRACT FROM AUTHOR]

Background: Extensively drug-resistant Acinetobacter baumannii (XDRAB) can acquire drug resistance genes, which are rapidly cloned and transmitted, leading to worldwide spread and posing significant treatment challenges. This study aimed to clarify effective treatment methods during XDRAB infection and factors affecting patient prognosis. Methods: Clinical features, treatment, and prognosis of 65 patients with hospital-acquired XDRAB pneumonia clinically diagnosed at Guangzhou First People's Hospital between January 2019 and December 2020 were retrospectively analyzed. Results: Of 65 subjects, only 37 survived. There was no significant difference in anti-A. baumannii activity according to type or combination of antibiotics administered between patients that survived and those that died (p > 0.05). The use of antibacterial drugs during infection did not effectively improve clinical outcomes. Advanced age, multiple organ failure, and disease severity were significantly negatively correlated while effective airway management was positively associated with bacterial clearance (p < 0.05). In multivariate analysis, age and APACHE score were independent risk factors affecting prognosis. Tracheotomy during infection was a protective factor contributing to survival (p < 0.05). Advanced age and disease severity independently affected patient prognosis, while use and type of antibacterial treatment did not substantially affect the prognosis. Conclusions: Advanced age and severe disease are independent risk factors that affect patient prognosis. Timely and effective airway management is key to improving the prognosis of patients with hospital-acquired XDRAB infection. [ABSTRACT FROM AUTHOR]

Background: Drug-resistant tuberculosis has continued to be a serious global health threat defined by complexity as well as higher morbidity and mortality wherever it occurs, Zambia included. However, the paucity of information on drug-susceptibility patterns of both first-line and second-line anti-tuberculosis (anti-TB) drugs, including the new and repurposed drugs used in the management of drug-resistant tuberculosis in Zambia, was the major thrust for conducting this study. Methods: A total of 132 bacteriologically confirmed TB isolates were collected from patients with pulmonary TB during the period from April 2020 to December 2021 in Southern and Eastern Provinces of Zambia. Drug-resistance profiles were determined according to four first-line and five second-line anti-TB drugs. Standard mycobacteriological methods were used to isolate and determine phenotypic drug susceptibility. Data on the participants' social–demographic characteristics were obtained using a pre-test checklist. Results: Overall, the prevalence of resistance to one or more anti-TB drugs was 23.5% (31/132, 95% CI: 16.5–31.6%). A total of 9.8% (13/132, 95% CI: 5.3–16.2%) of the patients had multidrug-resistant TB and 1.2% were new cases, while 25.5% had a history of being previously treated for TB. Among those with mono-resistant TB strains, isoniazid (INH) resistance was the highest at 9.8% (13/132, 95% CI: 5.3–16.2%). Two (2/31) (6.5%) XDR-TB and one (1/31) (3.2%) pre-XDR-TB cases were identified among the MDR-TB patients. Previously treated patients were 40 times more likely (OR; 40.3, 95% CI: 11.1–146.5%) to have drug-resistant TB than those who had no history of being treated for TB. Conclusion: This study has established a high rate of multidrug-resistant TB and has further identified both pre-XDR- and XDR-TB. There is a need to intensify surveillance of MDR- and XDR-TB to inform future guidelines for effective treatment and monitoring. [ABSTRACT FROM AUTHOR]

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is the leading cause of mortality worldwide due to a single bacterial pathogen. Of concern is the negative impact that the COVID-19 pandemic has had on the control of tuberculosis (TB) including drug-resistant forms of the disease. Antimicrobial resistance increases the likelihood of worsened outcomes in TB patients including treatment failure and death. Multidrug-resistant (MDR) strains, resistant to first-line drugs isoniazid and rifampin, and extensively drug-resistant (XDR) strains with further resistance to second-line drugs (SLD), threaten control programs designed to lower TB incidence and end the disease as a public health challenge by 2030, in accordance with UN Sustainable Development Goals. Tackling TB requires an understanding of the pathways through which drug resistance emerges. Here, the roles of acquired resistance mutation, and primary transmission, are examined with regard to XDR-TB. It is apparent that XDR-TB can emerge from MDR-TB through a small number of additional resistance mutations that occur in patients undergoing drug treatment. Rapid detection of resistance, to first-line drugs and SLD, at the initiation of and during treatment, and prompt adjustment of regimens are required to ensure treatment success in these patients. Primary transmission is predicted to make an increasing contribution to the XDR-TB caseload in the future. Much work is required to improve the implementation of the World Health Organization-recommended infection control practices and block onward transmission of XDR-TB patients to contacts including health-care workers. Finally, limiting background resistance to fluoroquinolones in pre-XDR strains of M. tuberculosis will necessitate better antimicrobial stewardship in the broader use of this drug class.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) producing the Verona integron‒encoded metallo-β-lactamase (VIM) are highly antimicrobial drug-resistant pathogens that are uncommon in the United States. We investigated the source of VIM-CRPA among US medical tourists who underwent bariatric surgery in Tijuana, Mexico. Cases were defined as isolation of VIM-CRPA or CRPA from a patient who had an elective invasive medical procedure in Mexico during January 2018‒December 2019 and within 45 days before specimen collection. Whole-genome sequencing of isolates was performed. Thirty-eight case-patients were identified in 18 states; 31 were operated on by surgeon 1, most frequently at facility A (27/31 patients). Whole-genome sequencing identified isolates linked to surgeon 1 were closely related and distinct from isolates linked to other surgeons in Tijuana. Facility A closed in March 2019. US patients and providers should acknowledge the risk for colonization or infection after medical tourism with highly drug-resistant pathogens uncommon in the United States.

ABSTRACT: Objectives: The aim of this study was to explore the relationship between cefiderocol pharmacokinetic/pharmacodynamic (PK/PD) target attainment and microbiological outcome in critically ill patients affected by extensively drug-resistant Acinetobacter baumannii (XDR-AB) bloodstream infection (BSI) and/or ventilator-associated pneumonia (VAP). Methods: Patients who received compassionate use of cefiderocol to treat documented XDR-AB infections at the intensive care unit of the IRCCS Azienda Ospedaliero–Universitaria of Bologna and who underwent therapeutic drug monitoring (TDM) from 15 March 2021 to 30 April 2021 were retrospectively assessed. Cefiderocol trough concentration (Cmin) was determined at steady-state, and the free fraction (fCmin) was calculated according to a plasma protein binding of 58%. The fCmin/MIC ratio was selected as a pharmacodynamic parameter of cefiderocol efficacy and was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if

Acinetobacter baumannii (A. baumannii) is now considered a highly resistant pathogen to various types of antibiotics. Therefore, tracking the source of its prevalence and continuous control is crucial. This study aimed to determine antibiotic resistance and perform various molecular typing methods on clinical isolates of A. baumannii isolated from hospitalized burn patients in Shahid Motahari Burn Hospital, Tehran, Iran. Hospital isolates were confirmed by phenotypic and molecular methods. Then the sensitivity to different antibiotics was determined using the minimum inhibitory concentration (MIC) method. In order to perform molecular typing, three-locus dual assay multiplex polymerase chain reaction (PCR), multiple-locus variable-number tandem repeat analysis (MLVA), and multilocus sequence typing (MLST) methods were used. Among the 60 isolates collected, the frequencies of multidrugresistant (MDR) and extensively drug-resistant (XDR) isolates were 90 and 10%, respectively. The most effective antibiotics were colistin with 100% and tigecycline with 83.33% sensitivity. Isolates were 100% resistant to piperacillin/ tazobactam and cephalosporins, and 68.3% were resistant to carbapenem. The results of multiplex PCR showed five groups that international clone I (IC I) and IC II were the most common. The MLVA method identified 34 MLVA types (MTs), 5 clusters, and 25 singletons. Multilocus sequence typing results for tigecycline-resistant isolates showed seven different sequence types (STs). Increasing antibiotic resistance in A. baumannii isolates requires careful management to control and prevent the occurrence of the pre-antibiotic era. The results of this study confirm that the population structure of A. baumannii isolates has a high diversity. More extensive studies are needed in Iran to better understand the epidemiology of A. baumannii. [ABSTRACT FROM AUTHOR]

The objective was to compare clinical characteristics, outcomes, and economic differences in complicated urinary tract infections (cUTI) caused by extensively drug-resistant Pseudomonas aeruginosa (XDR P. aeruginosa) and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-K. pneumoniae). A retrospective study was conducted at a tertiary care hospital. Patients with XDR P. aeruginosa and ESBL-K. pneumoniae cUTIs were compared. The primary outcome was clinical failure at day 7 and at the end of treatment (EOT). Secondary outcomes: 30- and 90-day mortality, microbiological eradication, and economic cost. Two-hundred and one episodes were included, of which 24.8% were bloodstream infections. Patients with XDR P. aeruginosa cUTI more frequently received inappropriate empirical therapy (p < 0.001). Nephrotoxicity due to antibiotics was only observed in the XDR P. aeruginosa group (26.7%). ESBL-K. pneumoniae cUTI was associated with worse eradication rates, higher recurrence, and higher infection-related readmission. In multivariate analysis, XDR P. aeruginosa was independently associated with clinical failure on day 7 of treatment (OR 4.34, 95% CI 1.71–11.04) but not at EOT, or with mortality. Regarding hospital resource consumption, no significant differences were observed between groups. XDR P. aeruginosa cUTI was associated with worse early clinical cures and more antibiotic side effects than ESBL-K. pneumoniae infections. However, no differences in mortality or in hospitalization costs were observed. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhi (S. Typhi) is a Gram-negative pathogen that causes typhoid fever in humans. Though many serotypes of Salmonella spp. are capable of causing disease in both humans and animals alike, S. Typhi and S. Paratyphi are common in human hosts only. The global burden of typhoid fever is attributable to more than 27 million cases each year and approximately 200,000 deaths worldwide, with many regions such as Africa, South and Southeast Asia being the most affected in the world. The pathogen is able to cause disease in hosts by evading defense systems, adhesion to epithelial cells, and survival in host cells in the presence of several virulence factors, mediated by virulence plasmids and genes clustered in distinct regions known as Salmonella pathogenicity islands (SPIs). These factors, coupled with plasmid-mediated antimicrobial resistance genes, enable the bacterium to become resistant to various broad-spectrum antibiotics used in the treatment of typhoid fever and other infections caused by Salmonella spp. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains in many countries of the world has raised great concern over the rise of antibiotic resistance in pathogens such as S. Typhi. In order to identify the key virulence factors involved in S. Typhi pathogenesis and infection, this review delves into various mechanisms of virulence, pathogenicity, and antimicrobial resistance to reinforce efficacious disease management. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is the leading cause of mortality worldwide due to a single bacterial pathogen. Of concern is the negative impact that the COVID-19 pandemic has had on the control of tuberculosis (TB) including drug-resistant forms of the disease. Antimicrobial resistance increases the likelihood of worsened outcomes in TB patients including treatment failure and death. Multidrug-resistant (MDR) strains, resistant to first-line drugs isoniazid and rifampin, and extensively drug-resistant (XDR) strains with further resistance to second-line drugs (SLD), threaten control programs designed to lower TB incidence and end the disease as a public health challenge by 2030, in accordance with UN Sustainable Development Goals. Tackling TB requires an understanding of the pathways through which drug resistance emerges. Here, the roles of acquired resistance mutation, and primary transmission, are examined with regard to XDR-TB. It is apparent that XDR-TB can emerge from MDR-TB through a small number of additional resistance mutations that occur in patients undergoing drug treatment. Rapid detection of resistance, to first-line drugs and SLD, at the initiation of and during treatment, and prompt adjustment of regimens are required to ensure treatment success in these patients. Primary transmission is predicted to make an increasing contribution to the XDR-TB caseload in the future. Much work is required to improve the implementation of the World Health Organization-recommended infection control practices and block onward transmission of XDR-TB patients to contacts including health-care workers. Finally, limiting background resistance to fluoroquinolones in pre-XDR strains of M. tuberculosis will necessitate better antimicrobial stewardship in the broader use of this drug class. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are usually multidrug resistant (MDR) and cause serious therapeutic problems. Colistin is a critical last-resort therapeutic option for MDR bacterial infections. However, increasing colistin use has led to the emergence of extensively drug-resistant (XDR) strains, raising a significant challenge for healthcare. In order to gain insight into the antibiotic resistance mechanisms of CRKP and identify potential drug targets, we compared the molecular characteristics and the proteomes among drug-sensitive (DS), MDR, and XDR K. pneumoniae strains. All drug-resistant isolates belonged to ST11, harboring blaKPC and hypervirulent genes. None of the plasmid-encoded mcr genes were detected in the colistin-resistant XDR strains. Through a tandem mass tag (TMT)-labeled proteomic technique, a total of 3531 proteins were identified in the current study. Compared to the DS strains, there were 247 differentially expressed proteins (DEPs) in the MDR strains and 346 DEPs in the XDR strains, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that a majority of the DEPs were involved in various metabolic pathways, which were beneficial to the evolution of drug resistance in K. pneumoniae. In addition, a total of 67 DEPs were identified between the MDR and XDR strains. KEGG enrichment and protein–protein interaction network analysis showed their participation in cationic antimicrobial peptide resistance and two-component systems. In conclusion, our results highlight the emergence of colistin-resistant and hypervirulent CRKP, which is a noticeable superbug. The DEPs identified in our study are of great significance for the exploration of effective control strategies against infections of CRKP. [ABSTRACT FROM AUTHOR]

Extensively drug-resistant and hypervirulent Klebsiella pneumoniae (XDR-hvKp) is a new problem for patients in Intensive Care Unit (ICU) and can become an even more severe threat if resistant to tigecycline, considered one of the 'last lines of defense' drugs. This study collected seven non-replicated tigecycline-resistant XDR-hvKp from seven patients and performed genome analysis and epidemiological investigation using whole genome equencing (WGS) and other methods. All strains in this study were identified as ST11-KL64 and showed high resistance to antibiotics such as β-lactams, aminoglycosides, quinolones, and tigecycline, and one strain was also resistant to colistin. All strains were determined to be hvKp by the results of serum resistance assay and Galleria mellonella infection models. All strains had resistance genes blaCTX-M- 65,b/aKPC-2,b/aLAP-2,b/aTEM-1B, rmtB, and qnrSl and virulence factors such as rmpA, rmpA2, and aerobactin (iucABCD, iutA). The expression of the AcrAB- TolC efflux pump was upregulated in all strains, and the expression levels of the gene pmrK was significantly upregulated in colistin-resistant strain DP compared to colistin-sensitive strain WT in this study. In conclusion, we described an outbreak caused by tigecycline-resistant XDR-hvKp in the ICU of a teaching hospital in southwest China. The spread of these superbugs poses a great threat to patients and therefore requires us to closely monitor these XDR-hvKp and develop relevant strategies to combat them. [ABSTRACT FROM AUTHOR]

Objective: Sepsis due to the drug resistant infections is associated with the higher mortality rates in an intensive care unit (ICU). The aim of this study was to determine the demographic characteristics of the deceased critically ill patients, prevalence of the sepsis, and extensively drug resistant infectious-related (XDR) deaths within a year in the ICU. Materials and Methods: The data of patients who died in the ICU between January 1, 2019 and 2020 was retrospectively analyzed. Results: Out of 525 patients admitted to the ICU, 269 of them died. One hundred fifty-one of those deceased patients (56.1%) were in medical and 118 (43.9%) in the surgical ICU. Their mean age was 70.5±15 years and 126 (46.8%) of them were female. The mean Acute Physiology and Chronic Health Evaluation-II, Glasgow coma score, Sequential Organ Failure Assessment scores at ICU admission were 23.4±20.9, 9.8±4.4, and 8.2±3.6, respectively. A few reasons for the ICU admission were: respiratory failure (34.9%), neurologic dysfunction (19%), sepsis (17.8%), and cardiovascular failure (16%). Infection occurred in the 231 (85.9%) patients. Of the 109 (40.5%) deceased patients with the diagnosis of sepsis, 48 (40%) of them were admitted in the ICU with sepsis. The most common site of infection was the respiratory system (34.6%). Septic shock was seen in 170 patients (63.2%) and renal replacement therapy was needed in 61 (22.7%) of them. XDR developed in 34.6% of the deceased patients and was more frequent among those with an antibiotic usage before the ICU admission (p=0.02). The mean length of stay at hospital before the ICU admission and length of the ICU stay were 22±25.8 and 10.1±12.7 days, respectively. The number of the deceased medical patients were significantly higher than the surgical patients (p=0.018). Conclusion: The deceased critically ill medical patients were higher than the surgical patients. A total of 40% of the deceased critically ill patients were diagnosed with a sepsis, and one third of them had XDR infection. XDR infections were more frequent among the patients with an antibiotic usage before the ICU admission. [ABSTRACT FROM AUTHOR]

Objectives: Individuals infected with extensively drug-resistant (XDR) Acinetobacter baumannii are difficult to cure and have a high mortality rate. In this study, we compared the genomic and phenotypic differences between XDR and non-multidrug-resistant (MDR) A. baumannii and further characterized hypervirulent XDR A. baumannii., Methods: A total of 1,403 Acinetobacter isolates were collected from patients with bacteremia between 1997 and 2015. Antimicrobial susceptibility test was performed to categorize isolates into non-MDR, MDR, and XDR groups. The presence of selected virulence-associated genes was determined by PCR. Bacterial phenotypes, including iron acquisition, biofilm formation, capsule production, and virulence to larvae and mice, were determined., Results: Multilocus sequence types revealed the high prevalence of ST2 (81.6%) and ST129 (18.4%) among 49 XDR isolates and sequence types of 18 non-MDR isolates were more diverse. Virulence-associated phenotypic assays showed that XDR isolates had higher iron acquisition ability and capsule production and higher virulence to Galleria mellonella larvae. However, their biofilm formation ability was lower compared to that of non-MDR isolates. XDR isolates contained more virulence genes, tonB, hemO, abaI, and ptk, while non-MDR isolates contained more pld and ompA. Twenty-one XDR isolates caused <20% larvae survival rate after 7 days post-infection were defined as hypervirulent XDR isolates. Among them, isolates 1677 (ST129) and 929-1 (ST2) also caused the death of all infected mice within two days., Conclusion: Some subpopulations of highly drug-resistant ST2 also exhibit high virulence. Therefore, it is of utmost importance to continue monitoring the spread of hypervirulent XDR A. baumannii isolates., Competing Interests: Declaration of competing interest The authors report that there are no competing interests to declare., (Copyright © 2024. Published by Elsevier Ltd.)