Search

This study aims to determine the characteristics and distribution of pathogenic bacteria in bloodstream infections (BSIs) by gram-negative bacteria in adults. One hundred seventy-one adult patients with BSIs who were treated at the Affiliated Hospital of Chengde Medical College between January 2018 and January 2020 were included in this study. The patients were assigned to the young- and middle-aged group and elderly group based on age. General patient data were analyzed. More elderly patients had BSIs and gram-negative bacteria than young- and middle-aged patients. The incidence of underlying diseases in elderly patients was significantly higher than the young- and middle-aged patients (P < .01). The composition of Brucella spp. was significantly different between the elderly group and young- and middle-aged group (P < .05). There were significantly more gallbladder infections in the elderly group than the young- and middle-aged group, and significantly fewer elderly patients had no definite infection sites than the young- and middle-aged group (P < .05). The incidence of complications and in-hospital mortality in the elderly group was higher than the young- and middle-aged group (P < .05). BSIs caused by gram-negative bacteria mainly involved elderly patients. BSIs were characterized by complications and a poor prognosis, as well as pathogenic bacteria and primary infection sites., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: The results of prediction models that stratify patients with sepsis and risk of resistant gram-negative bacilli (GNB) infections inform treatment guidelines. However, these models do not extrapolate well across hospitals., Objective: To assess whether patient case mix and local prevalence rates of resistance contributed to the variable performance of a general risk stratification GNB sepsis model for community-onset and hospital-onset sepsis across hospitals., Design, Setting, and Participants: This was a retrospective cohort study conducted from January 2016 and October 2021. Adult patients with sepsis at 10 acute-care hospitals in rural and urban areas across Missouri and Illinois were included. Inclusion criteria were blood cultures indicating sepsis, having received 4 days of antibiotic treatment, and having organ dysfunction (vasopressor use, mechanical ventilation, increased creatinine or bilirubin levels, and thrombocytopenia). Analyses were completed in April 2024., Exposure: The model included demographic characteristics, comorbidities, vital signs, laboratory values, procedures, and medications administered., Main Outcomes and Measures: Culture results were stratified for ceftriaxone-susceptible GNB (SS), ceftriaxone-resistant but cefepime-susceptible GNB (RS), and ceftriaxone- and cefepime-resistant GNB (RR). Negative cultures and other pathogens were labeled SS. Deep learning models were developed separately for community-onset (patient presented with sepsis) and hospital-onset (sepsis developed ≥48 hours after admission) sepsis. The models were tested across hospitals and patient subgroups. Models were assessed using area under the receiver operating characteristic curve (AUROC) and area under precision recall curve (AUPRC)., Results: A total of 39 893 patients with 85 238 sepsis episodes (43 207 [50.7%] community onset; 42 031 [48.3%] hospital onset) were included. Median (IQR) age was 65 (54-74) years, 21 241 patients (53.2%) were male, and 18 830 (47.2%) had a previous episode of sepsis. RS contributed to 3.9% (1667 episodes) and 5.7% (2389 episodes) of community-onset and hospital-onset sepsis episodes, respectively, and RR contributed to 1.8% (796 episodes) and 3.9% (1626 episodes), respectively. Previous infections and exposure to antibiotics were associated with the risk of resistant GNB. For example, in community-onset sepsis, 375 RR episodes (47.1%), 420 RS episodes (25.2%) and 3483 of 40 744 (8.5%) SS episodes were among patients with resistance to antimicrobial drugs (P < .001). The AUROC and AUPRC results varied across hospitals and patient subgroups for both community-onset and hospital-onset sepsis. AUPRC values correlated with the prevalence rates of resistant GNB (R = 0.79; P = .001)., Conclusions and Relevance: In this cohort study of 39 893 patients with sepsis, variable model performance was associated with prevalence rates of antimicrobial resistance rather than patient case mix. This variability suggests caution is needed when using generalized models for predicting resistant GNB etiologies in sepsis.

Background: Febrile neutropenia (FN) is a common complication of stem cell transplantation., Aim: To evaluate the frequency of sepsis in patients with FN colonized with resistant Gram-negative bacteria (extended-spectrum β-lactamase (ESBL)-positive, multidrug-resistant (MDR) Pseudomonas aeruginosa) and the choice of primary antibiotic in colonized patients., Methods: This retrospective study analysed data from patients undergoing haematopoietic stem cell transplantation from January 2018 to September 2022. Data were extracted from the hospital information system., Findings: Carbapenem as the primary antibiotic of choice was chosen in 10.9% of non-colonized +/-AmpC patients, 31.5% of ESBL + patients, and 0% of MDR P. aeruginosa patients. Patients with FN and MDR P. aeruginosa colonization had a high prevalence of sepsis (namely 100%, P = 0.0197). The spectrum of sepsis appeared to be different, with Gram-negative bacilli predominating in the ESBL + group (OR: 5.39; 95% CI: 1.55-18.76; P = 0.0123). Colonizer sepsis was present in 100% of sepsis with MDR P. aeruginosa colonization (P = 0.002), all in allogeneic transplantation (P = 0.0003), with a mortality rate of 33.3% (P = 0.0384). The incidence of sepsis in patients with ESBL + colonization was 25.9% (P = 0.0197), with colonizer sepsis in 50% of sepsis cases (P = 0.0002), most in allogeneic transplantation (P = 0.0003)., Conclusion: The results show a significant risk of sepsis in FN with MDR P. aeruginosa colonization, a condition almost exclusively caused by the colonizer. At the same time, a higher risk of Gram-negative sepsis has been demonstrated in patients colonized with ESBL + bacteria., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Whether antibiotic de-escalation reduces the risk of subsequent antibiotic resistance is uncertain. We sought to determine if beta-lactam (BL) antibiotic de-escalation is associated with decreased incidence of new Gram-negative resistance in hospitalized patients with sepsis., Methods: In a retrospective cohort study, patients with sepsis who were treated with at least 3 consecutive days of BL antibiotics, the first 2 days of which were with a broad-spectrum BL agent defined as a spectrum score (SS) of ≥7 were enrolled. Patients were grouped into three categories: (1) de-escalation of beta-lactam spectrum score (BLSS), (2) no change in BLSS, or (3) escalation of BLSS. The primary outcome was the isolation of a new drug-resistant Gram-negative bacteria from a clinical culture within 60 days of cohort entry. Fine-Gray proportional hazards regression modeling while accounting for in-hospital death as a competing risk was performed., Findings: Six hundred forty-four patients of 7742 (8.3%) patients developed new gram-negative resistance. The mean time to resistance was 23.7 days yielding an incidence rate of 1.85 (95% confidence interval [CI]: 1.71-2.00) per 1000 patient-days. The lowest incidence rate was observed in the de-escalated group 1.42 (95% CI: 1.16-1.68) per 1000 patient-days. Statistically significant reductions in the development of new gram-negative resistance were associated with BL de-escalation compared to no-change (hazards ratio (HR) 0.59 [95% CI: .48-.73])., Conclusions: De-escalation was associated with a decreased risk of new resistance development compared to no change. This represents the largest study to date showing the utility of de-escalation in the prevention of antimicrobial resistance., Competing Interests: Potential conflicts of interest. M. H. K.’s efforts were supported by the Barnes-Jewish Hospital Foundation. B. F. T.’s contribution occurred while he was working at the University of Health Sciences and Pharmacy in St. Louis; he is now an employee of Melinta Therapeutics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases., Methods: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure., Results: Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%-76.1%, interquartile range 19.6%-41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] .77-.88, P < .0001; translating to absolute risk reduction of -3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source)., Conclusions: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Gram-negative bacteremia is a life-threatening infection with high morbidity and mortality. Its incidence is rising worldwide, and treatment has become more challenging due to emerging bacterial resistance. Little data is available on the burden and outcome of such infections in Lebanon., Methods: We conducted this retrospective study in four Lebanese hospitals. Data on medical conditions and demographics of 2400 patients diagnosed with a bloodstream infection based on a positive blood culture were collected between January 2014 and December 2020., Results: Most bacteremias were caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, with the more resistant organisms being hospital-acquired. Third-generation cephalosporin and quinolone resistance was steady throughout the study, but carbapenem resistance increased. Mortality with such infections is high, but carbapenem resistance or infection with Pseudomonas or Acinetobacter species were significant risk factors for poor outcomes., Conclusion: This is the first multi-center study from Lebanon on gram-negative bacteremia, resistance patterns, and factors associated with a poor outcome. More surveillance is needed to provide data to guide empirical treatment for bacteremia in Lebanon., (© 2024. The Author(s).)

Background: The worldwide prevalence of multi-drug resistance (MDR) in Gram-negative bacteria (GNB), particularly related to extended-spectrum beta-lactamases (ESBLs) and carbapenemases, poses significant global public health and clinical challenges., Objectives: To characterize ESBL-producing Gram-negative bacilli, within a pediatric hospital in Gaza using whole genome sequencing (WGS)., Methods: A total of 158 clinical isolates of Gram-negative bacilli were collected from Al-Nasser Pediatric Hospital. These isolates were tested for ESBL production using the double disk synergy test. The antibiotic susceptibility profile was determined using the Kirby Bauer method following the Clinical and Laboratory Standard Institute guidelines. Selected 15 phenotypically MDR isolates were whole-genome sequenced and characterized for their genome-based species identity and antibiotic resistance gene profile., Results: Of the 158 isolates, 93 (58.9%) were positive for ESBL production. The frequency of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Proteus mirabilis, and Serratia marcescens was 50%, 22.7%, 22.7%, 1.8%, 1.2%, and 1.2% respectively. The prevalence of ESBL among urine, pus, blood, and sputum was 64%, 44%, 23%, and 63.6%, respectively. Chloramphenicol, Imipenem, and Meropenem were the most effective antibiotics against ESBL producers. In sequenced isolates,  an average of six anti-microbial resistance (AMR) genes were noted per isolate, where one of them carried up to 13 antibiotic resistance genes. Carbapenem resistance genes such as bla KPC-2 (6.6%), bla PDC-36/12 (6.6%), and bla POM-1 (6.6%) were detected. All the sequenced E. coli isolates (n = 8) showed multiple resistance genes, mainly against β-lactamase (25.0%), aminoglycosides (37.5%), sulfonamides (37.5%), and genes conferring resistance to tetracyclines (25.0)., Conclusion: Our results showed a high prevalence of ESBL-producing GNB isolated from a pediatric hospital in the Gaza Strip. Various antibiotic resistance genes were identified, including those encoding ESBL and carbapenems. The results highlight the significant challenge posed by MDR in GNB and emphasize the need for effective antibiotic strategies. Given the high endemicity observed in various studies from Palestine, it is important to conduct clinical and molecular epidemiology research to identify risk factors, transmission patterns, and clinical outcomes associated with GNB strains that carry ESBL and carbapenem resistance genes., (© 2024. The Author(s).)

Background: Ralstonia pickettii is an aerobic Gram-negative non-fermentative bacillus. It is an opportunistic pathogen that has recently prompted nosocomial outbreaks. Although it has low virulence, it can cause a wide range of invasive diseases in immunosuppressive patients. The characteristics of R. pickettii-related central line-associated bloodstream infection (CLABSI) outbreak in pediatric hematopoietic stem cell transplant (HSCT) recipients are presented in this study., Materials and Methods: This was a single-center, retrospective analysis conducted at Bahcesehir University Goztepe Medicalpark Hospital . The clinical and laboratory characteristics of twelve children with Ralstonia-related CLABSIs were analyzed., Results: Of the twelve patients with R. pickettii growth, seven were female. The median age was 12.1 (2-17) years. Autologous HSCT was performed in two of the patients and allogeneic HSCT was performed in ten patients for both malignant and non-malignant diseases. In the conditioning regimens, all patients were given myeloablative therapy. Clinical sepsis was the most common presentation. As a result of the investigations, R. pickettii growth was observed in saline solutions. All cases were successfully treated with the appropriate antibiotic regimen and the bacteria was not found in repeat cultures. Catheter removal was required in two patients. Mortality was not observed in any patient as the outcome of the infection episode., Conclusion: The detection and control of the infectious source are critical in pediatric HSCT patients with severe immunosuppression, as medical equipment-related outbreaks can be life-threatening., Competing Interests: The authors declare that there is no conflict of interest.

Background: Our aim was to assess the impact of COVID-19 pandemic on mortality in patients hospitalised with Gram-negative bloodstream infections (GNBSIs)., Methods: A retrospective cohort study including cases of Escherichia coli, Klebsiella species and Pseudomonas aeruginosa in England (January 2015-December 2021) reported to UKHSA's Second Generation Surveillance System. The outcome was 30-day all-cause mortality. Multivariable logistic regression models were built, and adjusted Odds Ratios (ORs) with 95% confidence intervals were reported., Results: Total E. coli, Klebsiella spp. and P. aeruginosa infections were 206,030, 53,819 and 21,129, respectively. Compared to the pre-pandemic period, odds of death during the pandemic (March 2020 onwards) in E. coli, Klebsiella spp. and P. aeruginosa infections with no COVID-19 infection within 28-days of onset were 1.13 (1.08-1.18), 1.15 (1.07-1.25) and 1.09 (0.97-1.22), while odds in GNBSIs with an associated COVID-19 infection were 2.45 (2.26-2.66), 2.96 (2.62-3.34) and 3.15 (2.61-3.80), respectively. Asian patients with an associated COVID-19 infection were more likely to die during the pandemic compared to White patients (E. coli: OR 1.28 (0.95-1.71); Klebsiella spp. OR 1.59 (1.20-2.11); P. aeruginosa: OR 2.02 (1.23-3.31))., Conclusions: Patients suffering from a GNBSI had increased risk of death during the pandemic, with the risk higher in patients with an associated COVID-19 infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To understand the microbial profile and investigate the independent predictors for healthcare-associated pneumonia (HCAP) pertinaciously caused by isolates of multidrug-resistant (MDR) Gram-negative bacteria (GNB)., Methods: Multicenter ICU patients who received appropriate antibiotic treatments for preceding pneumonia due to MDR GNB isolates and subsequently developed HCAP caused by either MDR GNB (n = 126) or non-MDR GNB (n = 40) isolates in Taiwan between 2018 and 2023 were enrolled. Between the groups of patients with HCAP due to MDR GNB and non-MDR GNB, the proportions of the following variables, including demographic characteristics, important co-morbidities, nursing home residence, physiological severity, intervals between two hospitalizations, steroid use, the tracheostomy tube use alone, ventilator support, and the predominant GNB species involving HCAP, were analyzed using the chi-square test. Logistic regression was employed to explore the independent predictors for HCAP persistently caused by MDR GNB in the aforementioned variables with a P-value of <0.15 in the univariate analysis., Results: MDR-Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii complex were the three predominant species causing HCAP. Chronic structural lung disorders, diabetes mellitus, intervals of ≤30 days between two hospitalizations, use of the tracheostomy tube alone, and prior pneumonia caused by MDR A. baumannii complex were shown to independently predict the HCAP tenaciously caused by MDR GNB. Conversely, the preceding pneumonia caused by MDR P. aeruginosa was a negative predictor., Conclusion: Identifying predictors for HCAP persistently caused by MDR GNB is crucial for prescribing appropriate antibiotics., Competing Interests: Declaration of competing interest None are declared., (Copyright © 2024. Published by Elsevier B.V.)

Infections caused by multidrug-resistant (MDR) bacteria are typically associated with high morbidity and mortality, especially in vulnerable individuals such as patients with prolonged hospitalizations, immunocompromised individuals, and the elderly. This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (C/A), meropenem/vaborbactam (M/V), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Italian Drug Agency (AIFA) monitoring records for inpatients have been collected and analyzed, assessing the characteristics of the patients involved. Adverse drug reactions (ADRs) and drugs involved have been reported using a descriptive analytical approach. All data have been collected retrospectively from patient's medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up. Despite the introduction of new antibacterial drugs active against Gram-negative bacteria is improving the clinical scenario, it is crucial that the use of new antibacterial drugs be implemented by appropriate antimicrobial stewardship, surveillance programs, and monitoring efforts to prevent further spread of resistance. This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 10 9 /L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI., (© 2024. The Author(s).)

Background: The incidence of metastatic complications in Gram-negative bloodstream infection (GN-BSI) remains undefined. This retrospective cohort study examines the incidence and predictors of complications within 90 days of GN-BSI., Methods: Patients with GN-BSIs hospitalized at two Prisma Health-Midlands hospitals in Columbia, South Carolina, USA from 1 January 2012 through 30 June 2015 were included. Complications of GN-BSI included endocarditis, septic arthritis, osteomyelitis, spinal infections, deep-seated abscesses, and recurrent GN-BSI. Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine incidence and risk factors of complications, respectively., Results: Among 752 patients with GN-BSI, median age was 66 years and 380 (50.5%) were women. The urinary tract was the most common source of GN-BSI (378; 50.3%) and Escherichia coli was the most common bacteria (375; 49.9%). Overall, 13.9% of patients developed complications within 90 days of GN-BSI. The median time to identification of these complications was 5.2 days from initial GN-BSI. Independent risk factors for complications were presence of indwelling prosthetic material (hazards ratio [HR] 1.73, 95% confidence intervals [CI] 1.08-2.78), injection drug use (HR 6.84, 95% CI 1.63-28.74), non-urinary source (HR 1.98, 95% CI 1.18-3.23), BSI due to S. marcescens, P. mirabilis or P. aeruginosa (HR 1.78, 95% CI 1.05-3.03), early clinical failure criteria (HR 1.19 per point, 95% CI 1.03-1.36), and persistent GN-BSI (HR 2.97, 95% CI 1.26-6.99)., Conclusions: Complications of GN-BSI are relatively common and may be predicted based on initial clinical response to antimicrobial therapy, follow-up blood culture results, and other host and microbiological factors., (© 2024. The Author(s).)

Background: Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes., Methods: A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing., Results: There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6-8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6-6.4)., Conclusions: GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials., Competing Interests: Potential conflicts of interest . D. L. P. reports research grants from Shionogi, Pfizer, Merck, bioMérieux, BioVersys, Gilead, and consultancies with AMR Action Fund, CARB-X, Innoviva, Pfizer, Merck, bioMérieux, Cepheid, Aurobac, Arrepath, Spero, Shionogi. P. N. A. H. reports research grants from Gilead, has served on advisory boards for OpGen, Merck, and Sandoz, and has received honoraria from OpGen, Sandoz, Pfizer, and BioMérieux. S. C. H. W. has received honoraria for participation in MSD expert forum for pneumococcal disease, which was paid to Children's Health Queensland. U. W. received travel and accommodation support for meeting attendances by Pfizer and Moderna. A. D. I. has received honoraria for lectures from BioMérieux and Gilead that were paid to the University of Queensland. L. J. S. is a recipient of grants from Swiss National Science Foundation, Swiss Personalized Health Network (SPHN), NHMRC, NIH, NOMIS Foundation, Doris and Thomas Ammann Foundation. L. J. S. is also on the advisory board for the Lancet Child Adolescent Health Journal. HC receives grants from NIH and NIAID and payment from Merck for participation in Molnupiravir clinical trial. H. C. receives payment as senior editor for Sanford Guide to Antimicrobial Therapy and holds stocks in Moderna and Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Antimicrobial resistance is a major global public health issue. Infections caused by resistant species are associated with higher mortality rates, longer hospital stays, medication failure, and rising medical costs. The World Health Organisation has declared multidrug resistance-associated infections as an epidemic of public health concern., Objective: This study aimed to evaluate the antimicrobial resistance profile and associated factors of hospital-acquired Gram-negative bacterial pathogens among hospitalized patients in Northeast Ethiopia., Materials and Methods: A health facility-based cross-sectional study was conducted among hospitalized patients from March 2021 to February 2022. About 810 clinical specimens were collected, transported, and processed from admitted patients following the standard bacteriological procedures. The clinical samples were inoculated onto blood agar, MacConkey agar, and chocolate agar. Furthermore, the species identification was done using gram reactions, colony morphology, and color and biochemical tests. Antimicrobial susceptibility tests, extended-spectrum beta-lactamase, and carbapenemase production were performed as per the clinical laboratory standard institute guidelines. For analysis, the information was entered into Epi-data and exported to SPSS. A P value of < 0.05 with a 95% confidence interval was considered as a statistically significant association., Results: Out of 810 clinical specimens, 285/810 (35.2%) developed bacterial infections. From the isolated bacteria, E. coli was the predominant bacteria accounting for 78/285 (27.4%) followed by K. pneumoniae, 69/285(24.42%), whereas P. vulgaris accounted for the least, 7/285 (2.5%). Overall, 132/285 (46.3%) and 99/285 (34.7%) of culture-positive patients were infected by extended-spectrum beta-lactamase and carbapenemase-producing bacteria. The overall multidrug resistance rate of the isolated bacteria was 89.4%. The highest antibiotic resistance rates were detected for doxycycline (92.9%), amoxicillin-clavulanic acid (83.9%), and ampicillin (93%). The least antibiotic resistance rate was observed for meropenem at 41.1% and amikacin at 1.7%, respectively., Conclusions and Recommendations: In the study area, significant health concerns include a range of hospital-acquired bacterial infections associated with elevated rates of multidrug resistance, Extended-spectrum beta-lactamase (ESBL), and carbapenemase-producing bacterial pathogens. Consequently, it is recommended to conduct drug-susceptibility testing of isolates and molecular detection at a national level to optimize antibiotic usage for treating prevalent bacterial infections in this area., (© 2024. The Author(s).)

Background: Swine dysentery, caused by Brachyspira hyodysenteriae, is a severe pig disease. Resistance to tylosins is common and resistance to tiamulin has been reported since the 1990s. Still, dysentery is not notifiable to authorities. The disease therefore escapes control from an overall population perspective. In Sweden, a program that aimed to control dysentery at national level was initiated in 2020, mainly due to the unexpected diagnosis of tiamulin resistant Brachyspira hyodysenteriae in 2016., Results: Through joint efforts of a network including farmers, government, animal health organisations and abattoirs it was concluded that outbreaks of dysentery had taken place in 25 herds between 2016 and 2019. By 1 January 2020, nine of these herds were still not declared free from the disease. From that date, the network decided that Brachyspira hyodysenteriae was to be cultured whenever dysentery could be suspected. Thus, 148, 157 and 124 herds were scrutinised for Brachyspira hyodysenteriae in 2020, 2021 and 2022, respectively, whereof five, three and two new herds were confirmed positive. By 31 December 2022, four herds were judged as impossible to sanitise. However, they posed no problem since they were identified by the network, pigs to and from these enterprises could be transported without jeopardising other herds. When Brachyspira hyodysenteriae was diagnosed in fattening herds purchasing growers, Brachyspira hyodysenteriae could not be detected in the delivering herds. That result, together with other observations, indicated that Brachyspira hyodysenteriae ought to be regarded as ubiquitous, although at a low level in healthy pigs., Conclusions: Eradication of dysentery contributed to substantial welfare and financial improvements in affected herds. Dysentery was controlled successfully at national level through the united efforts from competing stake holders, such as different abattoirs and animal health organisations. However, as Brachyspira hyodysenteriae was assumed to be ubiquitous, although at a low level in healthy pigs, the duration of the successful control of dysentery was concluded to only be transient. Without permanent monitoring for Brachyspira hyodysenteriae, the knowledge of the national status will rapidly decline to the level prior to the initiation of the control program., (© 2024. The Author(s).)

Infections with multidrug-resistant gram-negative bacterial species are a great concern in clinics in Germany. By limiting therapeutic options dramatically, these bacteria pose a significant threat to patient health and cause extensive pressure on hygiene systems and patient management. In Germany, the recommendations on how to deal with these bacteria are called MRGN classification, using the terms 3MRGN and 4MRGN for bacteria resistant to three or four major classes of antibiotics. To be resistant to this large number of antibiotics and become classified as 3MRGN or 4MRGN, bacterial strains need to acquire multiple resistance mechanisms with beta-lactamases, especially carbapenemases, being the most important ones. According to established surveillance systems like national reporting systems, KISS or the National Reference Centre, multidrug-resistant bacteria are constantly on the rise in Germany. Although several novel therapeutic options have been approved recently, these bacteria represent a constant challenge and it may be necessary to discuss if the present hygiene recommendations need an update for an efficient and targeted prevention of transmission., Competing Interests: Niels Pfennigwerth hat Honorare für Vorträge oder Beratungsleistungen von folgenden Firmen erhalten: Cepheid, Shionogi. Sören G. Gatermann hat Honorare für Vorträge von folgenden Firmen erhalten: BectonDickinson, BioMérieux, ThermoFisher., (Thieme. All rights reserved.)

Background: Diarrheal illness is a prominent public health worry in developing countries, resulting in high mortality among children. Sociodemographic characteristics and geographic settings are the main effective factors for the increased incidence of childhood diarrhea. Aeromonas is a neglected organism capable of causing dysentery and diarrhea. The aim of this systematic review and meta-analysis was to determine the prevalence of Aeromonas as an agent in the causation of diarrhea in Asian children. Methods: We conducted a systematic review using Web of Science, PubMed, Wiley Online Library, Science Direct, and Google Scholar for peer-reviewed articles published between January 2000 and February 2023. We considered studies that found Aeromonas in diarrheal stool. A random-effects model was used to determine the pooled prevalence of Aeromonas . Results: Our search returned 2,057 articles, with 17 articles from seven Asian nations being included in the systematic review. The pooled prevalence of Aeromonas was 4.5% (95% confidence interval [CI]: 2.9%-6.8%), with heterogeneity ( I 2 = 96.85; p < 0.001). There was a greater prevalence in areas with high population living in poverty (12.2%; 95% CI: 5.8%-24%) and lower-middle-income countries (5.0%; 95% CI: 2.7%-9.0%). In addition, the prevalence of Aeromonas was greater in South Asia (10.0%; 95% CI: 5.6%-17.2%), in India (12.9%; 95% CI: 6.8%-23%), and in countries with open defecation rate of 5%-25% (11.3%; 95% CI: 6.3%-19.2%). Conclusion: The prevalence of Aeromonas -associated diarrhea in children in Asia estimated in the present study highlighted the high burden of Aeromonas in some parts of Asia.

Objectives: Ceftolozane-tazobactam (C/T) is a combination of a cephalosporin and a β-lactamase inhibitor with activity against Gram-negative bacilli (GNB). The study aims were to evaluate the activity of C/T in vitro vs. comparators against clinical GNB isolated from Chinese paediatric patients., Methods: From 2017-2021, 660 GNB isolates were collected from 20 hospitals across China. The minimum inhibitory concentrations were tested using a Trek Diagnostic System (Thermo Fisher Scientific). Susceptibility was determined by CLSI broth microdilution and the results were interpreted according to CLSI M100 (2021) breakpoints., Results: GNB isolates were obtained from paediatric patients < 18 years old, mainly from the bloodstream (n = 146), intraperitoneal cavity (n = 138), lower respiratory (n = 278) and urinary tract (n = 96). Overall, C/T was active against 76.6% of 436 Enterobacterales, with a descending susceptibility rate of 100.0% to S. marcescens, 92.2% to E. coli, 83.3% to K. oxytoca, 66.7% to K. aerogenes, 66.7% to P. mirabilis, 58.6% to K. pneumoniae and 57.1% to E. cloacae. The susceptibility of P. aeruginosa to C/T was 89.4%, which was the highest among the β-lactam antibiotics and was second only to amikacin (92.9%). Isolates of respiratory tract infection (RTI) derived P. aeruginosa were highly susceptible (93.8%) to C/T, while <75% of isolates of RTI derived P. aeruginosa were susceptible to the other β-lactam antibiotics tested, except for ceftazidime-avibactam (91.2%)., Conclusion: GNBs collected from paediatric patients in China showed a high susceptibility to C/T making this drug combination an effective choice for treating the paediatric population, especially those infected with P. aeruginosa., Competing Interests: Competing interests The authors declare that they have no competing interests, except for Pengcheng Li who is an employee of MSD China., (Copyright © 2024. Published by Elsevier Ltd.)

Aeromonas species can cause a wide range of clinical infections. Several reports of drug resistance among the Aeromonas species have been reported, but our observations have differed. Here we present the changing susceptibility pattern of antibiotics for Aeromonas species over 14 years (January 2010-February 2024) at a tertiary care hospital in South India., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

The role of Aeromonas spp. in gastroenteritis is controversial due to varied clinical presentations and variable prevalence in asymptomatic. This study, conducted in Northern Israel, aimed to compare positivity rate and demographic characteristics of patients with Aeromonas-associated gastroenteritis (AAG) to asymptomatic, and examine the role of Aeromonas in AAG by comparing clinical and epidemiological characteristics between AAG and Campylobacter-associated gastroenteritis (CAG) patients. Results showed that 4.24%-4.81% of AAG patients had Aeromonas spp. in stools as a sole pathogen in 2020-2022, compared to 4.9% of asymptomatic. Analysis of 243 CAG patients versus 70 AAG patients revealed significantly less diarrhea, fever, abdominal pain, and muscle pain in AAG patients. Multivariate analysis identified higher Ct values, recent restaurant dining, and prolonged diarrhea as predictive factors for AAG versus CAG. In conclusion, similar positivity rates of Aeromonas spp. in symptomatic and asymptomatic making the distinction between true pathogen versus commensal bacteria difficult, unlike CAG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the microbiological epidemiology of carbapenemase-producing Gram-negative bacilli (CPGNB) isolated from blood during a 5-year period., Methods: A total of 80 isolates from 78 patients were finally included; fifty-five (70.5%) were men and the mean age was 60 years. Detection of carbapenemase production was performed by immunocromatography (IC) and polymerase chain reaction (PCR). Genotyping was carried-out by pulsedfield gel electrophoresis (PFGE) and multi-locus sequence typing (MLST), and characterization of carbapenemase-producing isolates was performed by whole genome sequencing (WGS)., Results: The main microorganisms isolated were K. pneumoniae (29.4%), E. cloacae (28.2%), A. baumannii (17.9%) and P. aeruginosa (15.3%). Overall, the most common carbapenemase in Enterobacterales was OXA-48 group (57.7%). The most common carbapenemase in non-fermenting bacilli was OXA-23 (60.8%). The most common ST in K. pneumoniae producing OXA-48 types was ST45 and in E. cloacae ST114, while in E. cloacae producing VIM types was ST78. In OXA-23 types, the most common clone in A. baumannii was ST2, whereas in P. aeruginosa producing IMP types was ST253., Conclusions: There was an increase in cases recorded in the years of highest incidence and severity of the SARS-CoV-2 pandemic, with a significant number of cases in patients admitted to the ICU. All bacteremias caused by A. baumannii were caused by the same clone, and 12 of the 14 cases caused by A. baumannii were part of outbreaks in the ICU., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Antibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU., Methods: In the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients., Results: A total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7-96.4%, 25.7-100%, 73.3-100%, and 89.2-100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0-96.8%, 0-100%, and 6.4-100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates., Conclusions: Based on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam-beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU., (© 2024. The Author(s).)

Background: The emergence and rapid spread of gram-negative bacteria resistant to carbapenems among newborns is concerning on a global scale. Nonetheless, the pooled estimate of gram-negative bacteria resistant to carbapenem that cause neonatal sepsis in developing nations remains unknown. Thus, this study aimed to determine the combined prevalence of gram-negative bacteria resistant to carbapenem in African newborns who were suspected of having sepsis., Methods: All studies published from January 1, 2010, up to December 30, 2023, from PubMed, Science Direct, Scopus electronic databases, and the Google Scholar search engine were researched. Isolates tested for carbapenem from neonates with sepsis, English language papers conducted in Africa, and cross-sectional and cohort studies papers were included. Using PRISMA guidelines, we systematically reviewed and meta-analyzed studies that assessed the prevalence of carbapenem-resistant gram-negative bacteria. The "Joanna Briggs Institute" was used critically to evaluate the quality of the included studies. The data analysis was carried out using STATA™ version 17. Heterogeneity across the studies was evaluated using Q and I 2 tests. The subgroup analysis was done and, funnel plot and Egger's regression test were used to detect publication bias. A sensitivity analysis was conducted., Results: All 36 studies were included in the meta-analysis and systematic review. The pooled prevalence of carbapenem resistance in Africa was 30.34% (95% CI 22.03-38.64%). The pooled estimate of gram-negative bacteria resistant to imipenem, and meropenem was 35.57% (95% CI 0.67-70.54%) and 34.35% (95% CI 20.04% - 48.67%), respectively. A. baumannii and Pseudomonas spp. had pooled prevalence of 45.9% (95% CI 33.1-58.7%) and 43.0% (95% CI 23.0-62.4%), respectively. Similarly, Pseudomonas spp. and A. baumannii also exhibited strong meropenem resistance, with a pooled prevalence of 29.2% (95% CI 4.8-53.5%) and 36.7% (95% CI 20.1-53.3%), respectively. E. coli and K. pneumoniae were the two most common isolates., Conclusion: There should be urgent antimicrobial stewardship practices, strengthened surveillance systems and effective treatment for neonates with sepsis. There was remarkable variation in resistance across the continent., (© 2024. The Author(s).)

Background: Cockroaches can pose a significant health risk in hospital environments because they may serve as reservoirs and vectors for nosocomial pathogens. Cockroaches harbor epidemiologically significant extended spectrum and metalo beta lactamase producing Gram negative bacterial pathogens, which complicate nosocomial infections., Objectives: The main aim of this study is to determine aetiology and phenotypic extended spectrum and metalo beta lactamase producing Gram negative bacteria pathogens from cockroaches collected in hospitals., Methods: A cross-sectional study was employed from February to May 2022 to determine the antibiotic resistance producing bacterial isolates from cockroaches by giving special emphasis to metalo beta lactamase and extended spectrum beta lactamase production from different wards of WSUCSH. Cockroaches were collected with hands wearing sterile gloves. External homogenate was prepared and incubated microbiologically by using different culture media and differentiated biochemically. Antimicrobial susceptibility testing was performed by disk diffusion method. ESBL production was conducted using double disc synergy method and double disk method was used to detect MBL enzyme detection. Descriptive statistics was used to determine prevalence and percentage., Result: Out of 245 cockroaches, 108 Gram negative bacteria were isolated. K. pneumoniae 29(26.9%) was the most predominant bacteria and Enetrobacter spp. 8(7.4%), was the least. All, K. pneumoniae, P. mirabilis, and Enterobacter isolates were pan-resistant to Ampicillin. P.aeruginosa and P.mirabilis antibiotics showed ≥ 80% resistant for amoxicillin/clavulanic acid antibiotics. Cefotaxime, ceftazidime, ceftriaxone and imipenem showed relative efficacy compared with other antibiotics. Out of 78 amoxicillin-clavulanic acid resistant isolates, 42(34.7%) were ESBL producers. ESBL production is more depicted by P. aeruginosa, A. baumannii, K. pneumoniae and E. coli. The overall prevalence of MBL production is 29(23.1%). K. pneumoniae P. aeruginosa, E.coli, A. baumannii, Enterobacter spp and K.oxytoca revealed MBL production., Conclusion: The overall prevalence of ESBL and MBL producing nosocomial agents from hospital cockroaches was 34.7% and 23.1% respectively. P.aeruginosa, A.baumannii, K.pneumoniae and E.coli showed pronounced ESBL production. All bacterial isolates except P. mirabilis and C. freundii showed MBL production. The needed to evaluate our antibiotic stewardship program and antibiotic resistance detection for treatment is mandatory. The impact of cockroach as a source of AMR should be sought., (© 2024. The Author(s).)

Background: Cupriavidus gilardii is an aerobic, gram-negative, motile, glucose-nonfermenting bacillus, first described in 1999. Typically, it exhibits low pathogenicity in humans, causing opportunistic infections primarily in individuals with compromised immune systems. This bacterium has been also found in various environmental sources such as plants and contaminated soils. Notably, there have been no documented cases of C. gilardii infections in animals., Case Presentation: This case report outlines a bovine neonatal diarrhea outbreak that occurred in Northern Greece, during which C. gilardii was isolated. Faecal samples from 5-day-old calves were collected and transported to the laboratory for further examination. Bacterial culture and next generation sequencing techniques were employed to confirm the presence of this bacterium in the samples. Following the isolation and identification of C. gilardii from the samples, an autogenous vaccine was produced and administered to the cows within the farm. Subsequent to vaccination, a progressive reduction in calf diarrhea and deaths was observed, leading to their eventual complete resolution. To the best of our knowledge, this represents the first documentation of C. gilardii isolation from cases of bovine neonatal diarrhea., Conclusion: This case report presents the first isolation case of C. gilardii from animal samples and more specifically from calf faecal samples. It represents an important observation, providing evidence that this opportunistic human pathogen could contribute to clinical symptoms in animals., (© 2024. The Author(s).)

Background: There was a reported increase in the antimicrobial consumption in hospitals during the COVID-19 pandemic, accompanied by an increase in infections due to multidrug-resistant (MDR) bacteria., Methods: This retrospective time series study from intensive care units in Buenos Aires examined changes in antibiotic consumption (defined daily doses/1000 patients/day), the incidence of Gram-negative bacilli (GNB) and the mechanism of resistance. Antibiotics were categorised into group 1 (agents against MDR GNB) and group 2 (agents against non-MDR infections). Bacteriological samples included respiratory samples and blood cultures. Periods were divided into pre-pandemic (July 2019 to March 2020) and pandemic (April 2020 to March 2022). Correlation coefficients (r) were analysed and the Mann-Whitney test was performed to compare both periods., Results: During the study period, GNB incidence, group 1 antibiotic consumption and resistance mechanisms increased, whereas antibiotics decreased in group 2. A significant positive correlation was seen between the consumption of antibiotics in group 1 and the incidence of GNB (r = 0.63; P < 0.001) and resistance (r = 0.52; P = 0.002). Significant differences were found between pre-pandemic and pandemic periods regarding the medians of group 1 consumption (520 [408-570] vs. 753 [495-851] DDD/1000 patients/day; P = 0.029), incidence of GNB (12 [10-13] vs. 43 [25-52.5] cases/month; P < 0.001) and resistance mechanisms (5 [4-8] vs. 17 [10-25] cases/month; P < 0.001), extended-spectrum beta lactamases (2 [1-2] vs. 6 [3-8] cases/month; P < 0.001) and metallo-beta-lactamases (0 [0-0] vs. 6 [1.75-8.5] cases/month; P < 0.001)., Conclusion: During the COVID-19 pandemic, the rise in GNB incidence and the amount of resistance mechanisms significantly correlated with the increase in consumption of agents against MDR strains., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Introduction: Polymyxins, the cationic lipopeptide antibiotics, are the last line of therapeutics against the MDR Gram-negative bacterial (GNB) pathogens. Unfortunately, the rising cases of polymyxin-resistant strains from across the globe have adversely impacted their utility. While the molecular mechanisms responsible for developing polymyxin resistance (PolR) are largely understood, the prevalence of PolR strains in India has not been investigated systematically. The current study was undertaken to primarily determine the prevalence of PolR strains in India. Moreover, the extent of the spread of mobile colistin resistance (mcr) genes among the GNB strains in India was also determined., Method: A systematic search for articles using the relevant inclusion and exclusion criteria was performed in the applicable databases for the period January 2015 to December 2023. The included 41 studies were subjected to a meta-analysis using the Comprehensive Meta-Analysis software (V4.0). Publication biases were assessed using funnel plots and Egger's regression analysis., Result: Considering a total of 41 studies including 24 589 bacterial isolates the present meta-analysis found the rate of PolR bacteria in India to be at 15.0% (95% CI: 11.2 to 19.8). Among the Indian States, Tamil Nadu topped with the highest prevalence of PolR at 28.3%. Investigating the contribution of the mcr genes, it was observed that among the PolR strains, 8.4% (95% CI: 4.8 to 14.3) were mcr positive., Conclusion: The study determined the prevalence of PolR strains in India at 15.0%, which is higher than that of the global average at 10%. The study also determined that 8.4% of the PolR strains carried the mcr genes. The mcr-positive strains reported from India could be an underestimation of the actual numbers due to the non-inclusion of mcr screening in many previous studies. This study provides insight into the state of the PolR situation in India, which may be useful to develop a monitoring strategy to contain the spread of such strains and preserve the efficacy of the polymyxins., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Stenotrophomonas maltophilia is a carbapenem-resistant Gram-negative pathogen increasingly responsible for difficult-to-treat nosocomial infections., Objectives: To describe the contemporary clinical characteristics and genome epidemiology of patients colonized or infected by S. maltophilia in a multicentre, prospective cohort., Methods: All patients with a clinical culture growing S. maltophilia were enrolled at six tertiary hospitals across Japan between April 2019 and March 2022. The clinical characteristics, outcomes, antimicrobial susceptibility and genomic epidemiology of cases with S. maltophilia were investigated., Results: In total, 78 patients were included representing 34 infection and 44 colonization cases. The median age was 72.5 years (IQR, 61-78), and males accounted for 53 cases (68%). The most common comorbidity was localized solid malignancy (39%). Nearly half of the patients (44%) were immunosuppressed, with antineoplastic chemotherapy accounting for 31%. The respiratory tract was the most common site of colonization (86%), whereas bacteraemia accounted for most infection cases (56%). The 30 day all-cause mortality rate was 21%, which was significantly higher in infection cases than colonization cases (35% versus 9%; adjusted HR, 3.81; 95% CI, 1.22-11.96). Susceptibility rates to ceftazidime, levofloxacin, minocycline and sulfamethoxazole/trimethoprim were 14%, 65%, 87% and 100%, respectively. The percentage of infection ranged from 13% in the unclassified group to 86% in genomic group 6A. The percentage of non-susceptibility to ceftazidime ranged from 33% in genomic group C to 100% in genomic groups 6 and 7 and genomic group geniculate., Conclusions: In this contemporary multicentre cohort, S. maltophilia primarily colonized the respiratory tract, whereas patients with bacteraemia had the highest the mortality from this pathogen. Sulfamethoxazole/trimethoprim remained consistently active, but susceptibility to levofloxacin was relatively low. The proportions of cases representing infection and susceptibility to ceftazidime differed significantly based on genomic groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The Clinical and Laboratory Standards Institute has published epidemiological cut-off values for susceptibility data generated at 22°°C and read after 44-48 h for florfenicol, oxolinic acid and oxytetracycline against Aeromonas salmonicida. The cut-off values for the minimum inhibitory concentration (MIC) and disc diffusion were derived from data obtained by 1 laboratory and 2 laboratories respectively. The present work reports the generation of susceptibility data from additional laboratories and the calculation of provisional cut-off values from aggregations of these data with previously published data. With respect to MIC data, the provisional cut-off values, derived from aggregations of the data from 4 laboratories, were ≤4 µg ml-1 for florfenicol, ≤0.0625 µg ml-1 for oxolinic acid and ≤1 µg ml-1 for oxytetracycline. For disc diffusion data, the provisional cut-off values derived from aggregations of the data from 5 laboratories were ≥30 mm for florfenicol, ≥32 mm for oxolinic acid and ≥25 mm for oxytetracycline. In addition, a cut-off value of ≥29 mm for ampicillin was derived from the aggregation of data from 4 laboratories.

Objectives: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI., Methods: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders., Results: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism., Conclusions: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Stenotrophomonas maltophilia was considered to be a low-virulence organism. But it has emerged as a prominent opportunistic pathogen in patients with certain risk factors. This study aimed to describe an outbreak experienced in our hospital with all dynamics while evaluating previous S. maltophilia outbreak reports. S. maltophilia isolates were obtained from a university hospital in Türkiye in a seven-months period. Antimicrobial resistance, type of infections, predisposing factors of infected patients, antibiotic therapy, outcome of infections, and outbreak source were investigated. Also, S. maltophilia outbreaks in the literature were reviewed. In the 12 months prior to the outbreak, prevalence rate of clinical samples including S. maltophilia was 7/1,000 patient per day, opposed to 113/1,000 patient per day during the outbreak. Although a large number of cases were observed in a short seven-month period, a source of contamination could not be detected. Stable mortality rates (or remaining close to the average) during outbreaks can be attributed to the careful attention paid by laboratory and clinic physicians during procedures. S. maltophilia has potential to spread outbreaks and infect patients in operating rooms and intensive care units during invasive procedures.

Background: Gram-negative bacteria with quinolone resistance and extended-spectrum beta-lactamases (ESBLs) present significant treatment challenges. This study evaluated the prevalence and characteristics of quinolone resistance in Gram-negative strains, investigating the relationship between plasmid-mediated quinolone resistance (PMQR), ESBLs, and integrons., Methods and Results: We collected 146 Gram-negative isolates from patients in three Palestinian hospitals. For quinolone resistance isolates, the presence and characterization of PMQR, β-lactamase genes and integrons were studied by PCR and sequencing. Out of 146 clinical isolates, 64 (43.8%) were resistant to quinolones, with 62 (97%) being multidrug-resistant (MDR) and 33 (51.5%) ESBL-producers. PMQR-encoding genes were present in 45 (70.3%) isolates, including aac(6')-Ib-cr (26.6%), qnrA (18.8%), qnrS1 (20.8%), and qnrB (6.4%). Bla CTX-M genes were detected in 50% (32/64) of isolates, with bla CTX-M-15 being the most common. Bla TEM-1 , bla SHV-1 and bla VIM genes were found in 13, 6, and 4 isolates, respectively. Class I integrons were found in 31/64 (48%) of isolates, with 14 containing gene cassettes conferring resistance to trimethoprim (dhfr17, dfrA12, dfrA1) and aminoglycosides resistance genes (aadA1, aadA2, aadA5, and aadA6)., Conclusions: This study found a high rate of quinolone resistance, ESBL and integrons in clinical Gram-negative isolates from our hospitals. Urgent measures are crucial, including implementing an antimicrobial resistance surveillance system, to control and continuously monitor the development of antimicrobial resistance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Patients with hematological diseases are considered to be at high risk for intestinal colonization by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the epidemiological data regarding risk factors and molecular characteristics of intestinal colonized CR-GNB isolates in this population are insufficient in China. A multicenter case‒control study involving 4,641 adult patients with hematological diseases from 92 hospitals across China was conducted. Following culture of collected rectal swabs, mass spectrometry and antimicrobial susceptibility tests were performed to identify GNB species and CR phenotype. Risk factors were assessed through retrospective clinical information. Whole-genome sequencing was used to analyze the molecular characteristics of CR-GNB isolates. This trial is registered with ClinicalTrials.gov as NCT05002582. Our results demonstrated that among 4,641 adult patients, 10.8% had intestinal colonization by CR-GNB. Of these, 8.1% were colonized by carbapenem-resistant Enterobacterales (CRE), 2.6% were colonized by carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 0.3% were colonized by carbapenem-resistant Acinetobacter baumannii (CRAB). The risk factors for CR-GNB colonization include male gender, acute leukemia, hematopoietic stem cell transplantation, β-lactam antibiotic usage, and the presence of non-perianal infections within 1 week. Compared with CRPA-colonized patients, patients using carbapenems were more likely to be colonized with CRE. NDM was the predominant carbapenemase in colonized CRE. This study revealed a high CR-GNB intestinal colonization rate among adult patients with hematological diseases in China, with CRE being the predominant one. Notably, a significant proportion of CRE exhibited metallo-β-lactamase production, indicating a concerning trend. These findings emphasize the importance of active screening for CR-GNB colonization in patients with hematological diseases.IMPORTANCECarbapenem-resistant Gram-negative bacteria (CR-GNB) has emerged as a significant threat to public health. Patients with hematological diseases are at high risk of CR-GNB infections due to their immunosuppressed state. CR-GNB colonization is an independent risk factor for subsequent infection. Understanding the risk factors and molecular characteristics of CR-GNB associated with intestinal colonization in patients with hematological diseases is crucial for empirical treatment, particularly in patients with febrile neutropenia. However, the epidemiology data are still insufficient, and our study aims to determine the intestinal colonization rate of CR-GNB, identify colonization risk factors, and analyze the molecular characteristics of colonized CR-GNB isolates., Competing Interests: The authors declare no conflict of interest.

Background: Multidrug-resistant Gram-negative bacteria (MDR-GNB) are prevalent in intensive care units (ICUs), leading to increased morbidity and mortality. Limited data on MDR-GNB in Indonesia prompted this study to determine the prevalence and risk factors associated with MDR-GNB colonization, enhancing screening strategies, and acquiring phenotypic and genotypic data on these bacteria., Methods: This analytical cross-sectional observational study included participants who met the criteria and were admitted to the ICU at Dr. Cipto Mangunkusumo Hospital from January to December 2022. We used multivariate analysis on the findings from rectal swab screening, sociodemographic, clinical, and microbiological examinations., Results: Out of 108 participants, 172 cultures comprised 165 Gram-negative isolates, four yeasts, and three with no growth. The prevalence of patients colonized with MDR-GNB was 51.85% (56/108), and the prevalence of MDR-GNB isolates was 39.53% (68/172), with the most common MDR-GNB being Escherichia coli (29.65%) and Klebsiella pneumoniae (19.44%). The most resistant gene found in ESBL was CTX-M (75%), and the carbapenemase producer gene was NDM (5.88%). Risk factors associated with MDR-GNB colonization were the length of stay before admission to the ICU (p = 0.003) and a history of previous antibiotic therapy (p = 0.036)., Conclusion: In this study, two risk factors were associated with the occurrence of MDR-GNB colonization, with the prevalence of MDR-GNB colonization in patients initially admitted to the ICU still quite high. Therefore, selecting screening patients based on risk factors at the time of initial admission to the ICU is crucial for infection control programs.

We aimed to determine the epidemiology and resistance patterns of Gram-negative bacteria, the risk factors and outcome of bloodstream infection (BSI). In all, 412 episodes in children who were hospitalized with the diagnosis of bacteremia were analyzed. The most common microorganisms were Klebsiella spp. (43.9%), Escherichia coli (13.5 %) and Acinetobacter spp. (10.6 %). Among isolates, 41.2 % were multidrug-resistant, 13.5 % were extensively drug-resistant and 0.4 % were pan-drug-resistant. Carbapenem resistance was revealed in 27.6 % of isolates. Carbapenem and colistin resistance increased over the years. The most common risk factors were the presence of a central-venous catheter and pediatric intensive care unit admission. Clinical response and infection-related mortality were significantly different in cases infected with carbapenem-resistant gram-negative (CRGN) vs carbapenem-susceptible gram-negative bacteria. The increase in multi-resistant Klebsiella spp. seems to be the biggest obstacles in fight against nosocomial infections. The increasing number of CRGN infections over the years affects both the clinical response and mortality rate of BSI., Competing Interests: Declaration of competing interest The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.

Introduction: Ovine foot rot is a highly contagious and multifactorial claw disease, caused by Dichelobacter nodosus (D. nodosus) and is the main cause of lameness in sheep. The aim of this cross-sectional study was to determine the prevalence of D. nodosus in western Austria both at animal and farm levels. Real-time PCR was evaluated in comparison with clinical and bacteriological investigations from interdigital foot swabs to detect D. nodosus-infected animals. In addition, the use of pooled four-foot swabs to detect foot rot was determined. In course of the study a total of 3156 sheep from 124 farms were examined for lameness and clinical signs of foot rot. The found flock prevalence of D. nodosus was 30,65 % with bacterial culture showing a sensitivity of 75,0 % and a specificity of 100,0 % (p < 0,001) respectively, compared with PCR. Furthermore, clinical foot rot scores (Ckorr = 0,87; p < 0,001) and lameness scores (Ckorr = 0,71; p < 0,001) highly correlated with the detection of D. nodosus by PCR. The result showed that the clinical examination can be used to identify animals infected with D. nodosus in flocks, but PCR must be used to confirm the diagnosis. D. nodosus could be detected equally well with risk-based pools-of-five samples as with undiluted samples (p < 0,001), suggesting that a pool-of-five samples might be a suitable and cost-effective method for detecting D. nodosus in sheep flocks. This study provides an overview of foot rot in Tyrolean sheep flocks and outlines the possibilities and limitations of the various diagnostic tools for D. nodosus. Further studies to investigate possible influencing factors, including alpine pasturing, management factors and biosecurity predisposing to foot rot are necessary for the design of effective future control programs in alpine regions.

Background: Herbaspirillum species are nonfermenting, aerobic, helical or curved, Gram-negative bacteria belonging to the class Betaproteobacteria, order Burkholderiales. To date, only a few studies have reported on the epidemiology, clinical symptoms, antibiotic susceptibility profiles, treatment and outcomes of Herbaspirillum huttiense -related infections in pediatric patients., Methods: The aim of this study was to present 3 years of H.huntiense data, antibiotic susceptibility profiles, systemic antibiotics and antibiotic lock therapy (ALT) options and clinical outcomes., Results: Fourteen episodes of infection in 12 patients were included in this retrospective study. The patients had a male/female ratio of 1:1 and a median age of 160.5 months (range, 3-198 months). Catheter-related bloodstream infection (CRBSI) was detected in 11 patients. Only 1 patient developed catheter-related infective endocarditis. The patient's catheter was removed, and she was successfully treated with systemic antibiotics for 4 weeks. Systemic antibiotics were used in all infections related to H. huttiense . In septic, critically ill patients, the catheter was removed, and systemic antibiotics were started. Port catheters were removed in 5 patients. ALT was performed in clinically stable patients. ALT using amikacin was administered to 6 patients through the port catheter. Two patients had a 2nd attack. After the 2nd ALT treatment, 1 patient cured, and the catheter of the other patient was removed due to persistent microbial growth in cultures. Antimicrobial susceptibility testing of the reported isolates showed susceptibility to meropenem (90%), ceftazidime (87%) and piperacillin/tazobactam (65%), with 92% resistance to colistin., Conclusion: H. huttiense is an emerging pathogen in CRBSI. Piperacillin/tazobactam, ceftazidime and meropenem appear to be good therapeutic options for the treatment of H. huttiense infections. ALT and systemic antibiotics can be used in H. huttiense -CRBSI to sterilize and preserve the central venous catheter., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Stenotrophomonas maltophilia is a nonfermenting gram-negative bacterium associated with multiple nosocomial outbreaks. Antibiotic resistance increases healthcare costs, disease severity, and mortality. Multidrug-resistant infections (such as S. maltophilia infection) are difficult to treat with conventional antimicrobials. This study aimed to investigate the isolation rates, and resistance trends of S. maltophilia infections over the past 19 years, and provide future projections until 2030. In total, 4466 patients with S. maltophilia infection were identified. The adult and main surgical intensive care unit (ICU) had the highest numbers of patients (32.2%), followed by the cardiology department (29.8%), and the paediatric ICU (10%). The prevalence of S. maltophilia isolation increased from 7% [95% confidence interval (CI) 6.3-7.7%] in 2004-2007 to 15% [95% CI 10.7-19.9%] in 2020-2022. Most S. maltophilia isolates were resistant to ceftazidime (72.5%), levofloxacin (56%), and trimethoprim-sulfamethoxazole (14.05%), according to our study. A consistent and significant difference was found between S. maltophilia-positive ICU patients and non-ICU patients (P = 0.0017) during the three-year pandemic of COVID-19 (2019-2021). The prevalence of S. maltophilia isolates is expected to reach 15.08% [95% CI 12.58-17.59%] by 2030. Swift global action is needed to address this growing issue; healthcare authorities must set priorities and monitor infection escalations and treatment shortages., (© 2024. The Author(s).)

This study aimed to investigate the epidemiological characteristics and trends over time of carbapenemase-producing (e.g., KPC, NDM, VIM, IMP, and OXA-48) Gram-negative bacteria (CPGNB). Non-duplicated multi-drug resistant Gram-negative bacteria (MDRGNB) were collected from the First Affiliated Hospital of Zhengzhou University from April 2019 to February 2023. Species identification of each isolate was performed using the Vitek2 system and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry according to the manufacturer's instructions. PCR detected carbapenem resistance genes in the strains, strains carrying carbapenem resistance genes were categorized as CPGNB strains after validation by carbapenem inactivation assay. A total of 5705 non-repetitive MDRGNB isolates belonging to 78 different species were collected during the study period, of which 1918 CPGNB were validated, with the respiratory tract being the primary source of specimens. Epidemiologic statistics showed a significant predominance of ICU-sourced strains compared to other departments. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were the significant CPGNB in Henan, and KPC and NDM were the predominant carbapenemases. Carbapenem-resistant infections in Henan Province showed an overall increasing trend, and the carriage of carbapenemase genes by CPGNB has become increasingly prevalent and complicated. The growing prevalence of CPGNB in the post-pandemic era poses a significant challenge to public safety., (© 2024. The Author(s).)

Nowadays, the three strongly beta-haemolytic spirochaetes, Brachyspira hyodysenteriae, Brachyspira suanatina and Brachyspira hampsonii are thought to be causative agents of swine dysentery, an economically devastating disease of grow-finish pigs characterised by severe mucohaemorrhagic diarrhoea. B. hyodysenteriae has been reported in most leading swine-producing regions. B. suanatina and B. hampsonii have been successfully recovered from faecal samples collected in a few countries only. The present study was performed in March 2023 on faecal samples originating from nine Polish finisher farms with 6,000 to 18,000 animals in a location. Samples were obtained from 40 diarrhoeic finishers. Nucleic acid extracted from the samples was analysed using multiplex PCR for Brachyspira spp. From a total of nine sample populations examined in our study, the genetic material of B. hampsonii was identified in two. To the best of our knowledge, this is the first report on molecular detection of B. hampsonii on pig farms outside North America, Belgium and Germany. Our research highlights the need for increased focus directed on laboratory testing strategies, the lack of which may perplex swine practitioners and severely hinder a definite diagnosis.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources., Competing Interests: AM received scientific grants from the Wellcome Trust DBT alliance and the Indian Council of Medical Research. MG received a research grant from Pfizer, payment for lecture from Shionogi, MSD, Pfizer and BioMerieux. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Freire, Pouch, Manesh and Giannella.)

The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same bacterial species and strain (6% vs 2%; P = .04). Persistent GN-BSI may be a marker of complicated infection., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio, Akagera, Aridis, Roche, grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from Infectious Diseases of America for his service as Associate Editor of Clinical Infectious Diseases, and a patent sepsis diagnostics pending; support for meetings and/or travel from Contrafect. J. T. T. reports being a Scientific Advisor for Resonantia Diagnostics, Inc, and grants or contracts from NIH and CDC. C. A. A. received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics, Harris County Public Health, NIH; support for meetings and/or travel from Infectious Diseases Society of America, American Society for Microbiology, Society of Hospital Epidemiology of America, European Society for Clinical Microbiology and Infectious Diseases, Merieux Foundation, Sociedad Argentina d Infectologia, Sociedad Chilena de Infectologia, Sociedad Colombiana de Infectologia, Panamerican Society for Infectious Diseases, Brazilian Society for Infectious Diseases; participation on the World Health Organization, Antibacterial Pipeline Advisory Group, NIH Grant Review Study Sections, Editor-in-Chief of Antimicrobial Agents and Chemotherapy. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae . In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was bla KPC, specifically bla KPC-2 [38.6% (88/228)] and bla KPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with bla VIM-2 and bla NDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was bla KPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with bla KPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were bla KPC-2 and bla KPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa , which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries., Competing Interests: This work was supported by MSD-Colombia, subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Juan Urrego-Reyes, Claudia C. Beltran, and Sebastian Medina are MSD employees. This did not interfere with the authors' ability to analyze, interpret the data, or prepare the manuscript.

Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To report trends in carbapenem resistance and difficult-to-treat resistance (DTR) among clinical isolates of Gram-negative priority pathogens collected by the ATLAS global surveillance program from 2018 to 2022., Methods: Reference broth microdilution testing was performed in a central laboratory for 79,214 Enterobacterales, 30,504 Pseudomonas aeruginosa, and 13,500 Acinetobacter baumannii-calcoaceticus complex isolates collected by a constant set of 157 medical centres in 49 countries in Asia Pacific (APAC), Europe (EUR), Latin America (LATAM), Middle East-Africa (MEA), and North America (NA) regions. MICs were interpreted by 2023 CLSI M100 breakpoints. β-lactamase genes were identified for meropenem-nonsusceptible (MIC ≥2 mg/L) Enterobacterales isolates., Results: Carbapenem-resistant Enterobacterales (CRE) detection increased (P < 0.05) in APAC, EUR, LATAM, and MEA regions and decreased in NA, while annual DTR percentages increased in all five regions. Carbapenem-resistant P. aeruginosa (CRPA; decreased in MEA region) and carbapenem-resistant A. baumannii-calcoaceticus complex (CRAB; decreased in MEA region and increased in EUR) remained relatively stable over time in all regions, although notably, annual percentages of CRAB and DTR A. baumannii-calcoaceticus complex isolates were consistently >25 percentage points lower in NA than in other regions. For all regions except NA, the majority of changes in CRE percentages could be attributed to hospital-acquired infections. Among meropenem-nonsusceptible Enterobacterales, KPC was the most frequent carbapenemase in NA and EUR each year. NDM was the most prevalent carbapenemase detected in 2022 in other global regions., Conclusion: CRE, CRPA, CRAB, and DTR rates vary among global regions over time highlighting the need for continuing surveillance to inform treatment strategies and antimicrobial stewardship., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study was to clarify the molecular epidemiology and clinical infection characteristics of Ralstonia pickettii and establish sequence typing system., Methods: 48 nonrepetitive Ralstonia pickettii strains were collected from January 2008 to December 2013 at the Chinese People's Liberation Army General Hospital (PLAGH) and were identified through a specific PCR experiment, 16 S rDNA experiment and VITEK 2 system to compare the identification accuracy. The sequence types of the strains were analyzed by multilocus sequence typing (MLST) method. The antibiotic sensitivity of these strains was determined with disc diffusion tests and broth microdilution method. The clinical data of Ralstonia pickettii infected patients were collected., Results: All of the 48 strains were identified as Ralstonia pickettii by VITEK 2 system. 30 and 34 strains were identified as Ralstonia pickettii by PCR and 16 S rDNA experiment respectively. ST9 was the most sequence types (STs) in these 18 STs of 42 strains. 42 strains were divided into 2 groups (A and B) and 18 genotypes. Ralstonia pickettii was sensitive to some cephalosporins, β-lactam/β-lactamase inhibitor, levofloxacin and trimethoprim/sulfamethoxazole. Cough, sputum, shortness of breath and pulmonary rales were the common clinical symptoms of most Ralstonia pickettii infected patients., Conclusion: We established a sequence typing system with a relatively fine resolution and the PCR assay is a faster and more sensitive method for clinical identification of Ralstonia pickettii. ST9 is the most common sequence types of Ralstonia pickettii. The most common clinical characteristics of Ralstonia pickettii infected patients were cough, sputum, shortness of breath and pulmonary rales., (© 2024. The Author(s).)