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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 blaKPC-2(6.6%), blaPDC-36/12 (6.6%), and blaPOM-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. [ABSTRACT FROM AUTHOR]

Fusobacterium nucleatum is a commensal pathogen typically found in the oral cavity, digestive tract, and urogenital system which has been associated with Lemierre's syndrome, periodontal diseases, sinusitis, endocarditis, and intra-abdominal and brain abscesses. Our case is of a 62-year-old male who presented with headaches, nausea, and vision loss. Brain imaging identified a right occipito-parietal brain abscess. Following surgery and abscess drainage, Fusobacterium nucleatum was isolated from intraoperative cultures, and the infectious disease service was consulted for antibiotic recommendations. Additional history uncovered that he had also been experiencing night sweats, generalized weakness and 40-pound weight loss for 2 months, and had a prior history of colon polyps and diverticulitis. Furthermore, the patient disclosed having substandard oral hygiene practices, particularly in relation to the care of his dental appliances. Despite negative blood cultures, suspicion for hematogenous seeding was high. Imaging ruled out periodontal disease, but identified a colovesical fistula and liver abscesses, indicating potential translocation of bacteria via portal circulation to his liver. Echocardiogram workup revealed a 1-cm mobile vegetation on the aortic valve. His course was complicated by breakthrough seizures, renal failure, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and he ultimately completed 16 weeks of antibiotics. This case illustrates an uncommon presentation of brain abscess in an immunocompetent adult, with a prior episode of diverticulitis as the probable primary infection source, leading to development of a colovesical fistula and bacterial dissemination to the liver, heart, and brain. It highlights the importance of a comprehensive diagnostic approach, including consideration of atypical pathogens in immunocompetent adults. [ABSTRACT FROM AUTHOR]

Organosulfur compounds derived from plants of the Allium genus, such as propyl‐propane‐thiosulfinate (PTS) and propyl‐propane‐thiosulfonate (PTSO), have been proposed as an alternative in antibiotic resistance. The aim of this study was to compare the activity of these substances with other antibiotics against clinical isolates of carbapenem‐resistant (CAR‐R) and carbapenem‐susceptible (CAR‐S) Gram‐negative bacteria. A total of 126 clinical isolates of CAR‐R and 155 CAR‐S bacteria were selected, including Enterobacterales, A. baumannii and P. aeruginosa. The antibiotic susceptibility of all isolates was assessed using the microdilution and Kirby–Bauer methods for PTS, PTSO, amoxicillin/clavulanate, piperacillin/tazobactam, cefotaxime, ceftazidime, cefepime, imipenem, ciprofloxacin, and amikacin. Both PTS and PTSO demonstrated in vitro bactericidal activity against CAR‐R Enterobacteriaceae and A. baumannii, with no significant difference in activity compared to their response against CAR‐S isolates. However, both compounds were less active against P. aeruginosa than against any of the other bacteria, regardless of their resistance to carbapenems. In all cases, the minimum inhibitory concentration values of PTSO were significantly lower than those of PTS. These findings offer valuable information about the potential antibacterial use of these substances, particularly against infections that currently have limited therapeutic options. [ABSTRACT FROM AUTHOR]

Abstract 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 blaKPC-2(6.6%), blaPDC-36/12 (6.6%), and blaPOM-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.

Abstract 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

Objective: Despite the increasing reports of blaNDM in Enterobacterales in Brazil, comprehensive whole genome sequencing (WGS) data remain scarce. To address this knowledge gap, our study focuses on the characterization of the genome of an New Delhi Metallo-β-lactamase (NDM)-1-producing Klebsiella quasipneumoniae subsp. quasipneumoniae (KQPN) clinical strain isolated in Brazil. Methods: The antimicrobial susceptibility profile of the A-73.113 strain was performed by agar dilution or broth microdilution following the Brazilian Antimicrobial Susceptibility Testing Committee/European Committee on Antimicrobial Susceptibility Testing recommendations. WGS was performed using the Illumina® NextSeq platform and the generated reads were assembled using the SPAdes software. The sequences obtained were submitted to the bioinformatics pipelines to determine the sequence type, resistome, plasmidome, and virulome. Results: The A-73.113 strain was identified as KQPN and was susceptible to polymyxins (MICs, ≤0.25 µg/mL), tigecycline (MIC, 0.5 µg/mL), ciprofloxacin (MIC, 0.5 µg/mL), and levofloxacin (MIC, 1 µg/mL). WGS analysis revealed the presence of genes conferring resistance to β-lactams (blaNDM-1, blaCTX-M-15, blaOXA-9, blaOKP-A-5, blaTEM-1), aminoglycosides [aph(3′)-VI, aadA1, aac(6′)-Ib], and fluoroquinolones (oqxAB, qnrS1, aac(6′)-Ib-cr]. Additionally, the presence of the plasmid replicons Col(pHAD28), IncFIA(HI1), IncFIB(K) (pCAV1099-114), IncFIB(pQil), and IncFII(K), as well as virulence-encoding genes fimABCDEFGHIK (type 1 fimbria), pilW (type IV pili), iutA (aerobactin), entABCDEFS/fepABCDG/fes (Ent siderophores), iroE (salmochelin), and allABCDRS (allantoin utilization) was verified. Furthermore, we found that the A-73.113 strain belongs to ST1040. Conclusions: Here we report the genomic characteristics of an NDM-1-producing KQPN ST1040 strain isolated from blood cultures in Brazil. These data will enhance our comprehension of how this species contributes to the acquisition and dissemination of blaNDM-1 in Brazilian nosocomial settings.

ABSTRACT: 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

Testing for dispersal of fluorescent gel from sink drains was sensitive for detection of sinks that dispersed gram-negative bacilli outside the bowl. Reducing the flow rate of sinks with rapid water inflow and/or elimination of obstruction leading to slow outflow was effective in preventing dispersal of fluorescence and gram-negative bacilli. [ABSTRACT FROM AUTHOR]

La résistance des bactéries à Gram négatif aux antibiotiques, en particulier les β-lactamines, est désormais considérée comme un problème majeur de santé publique. Les principaux mécanismes de résistance aux β-lactamines chez les entérobactéries sont la production de β-lactamases à spectre étendu (BLSE) ou de carbapénémases, qui hydrolysent pratiquement toutes les β-lactamines. Cependant, une proportion substantielle de bacilles à Gram négatif résistants aux carbapénèmes ne produit pas de carbapénémase mais combine la surproduction d'une céphalosporinase et/ou d'une BLSE avec une très faible hydrolyse des pénèmes et une perméabilité réduite de la membrane externe. L'arrivée de nouveaux agents antibactériens actifs sur certaines de ces souches multirésistantes, comme les nouveaux inhibiteurs de β-lactamines, a marqué un tournant dans le traitement et représente un réel progrès. La connaissance approfondie des mécanismes de résistance est cruciale pour le choix de la molécule la plus efficace, et leur prescription nécessite une collaboration étroite entre microbiologistes, infectiologues, et médecins de soins intensifs. Si ces molécules sont significativement plus actives contre les souches résistantes que celles précédemment disponibles, leur spectre d'activité ne couvre pas l'ensemble des mécanismes de résistance chez les Gram négatifs, ni chez les autres espèces bactériennes potentiellement impliquées dans les infections polymicrobiennes. L'utilisation de ces nouveaux composés ne modifie pas les schémas antibiotiques en termes de durée et d'indication de l'antibiothérapie combinée, qui restent très limités. Resistance of Gram-negative bacteria to the most widely used antibiotics, particularly β-lactams, is now considered as major public health problem. The main resistance mechanisms to β-lactams in Enterobacterales are the production of extended spectrum β-lactamases (ESBL) or carbapenemases, which hydrolyze virtually all β-lactams. However, a substantial proportion of carbapenem-resistant Gram-negative bacilli do not produce carbapenemase but combine overproduction of a cephalosporinase and/or ESBL with very low penem hydrolysis and reduced outer membrane permeability. The arrival of new antibacterial agents active on some of these multidrug-resistant strains, such as new β-lactam inhibitors, has marked a turning point in treatment and represents real progress. In-depth knowledge of resistance mechanisms is crucial to the choice of the most effective molecule, and their prescription requires close collaboration between microbiologists, infectious disease specialists and intensive care physicians. While these compounds are significantly more active against resistant strains than those previously available, their spectrum of activity does not cover all resistance mechanisms in Gram-negatives, nor in other bacterial species potentially involved in polymicrobial infections. The use of these new compounds does not alter antibiotic regimens in terms of duration and indication of combined antibiotic therapy, which remain very limited. [ABSTRACT FROM AUTHOR]

The emergence of nosocomial infections (NCI) in Intensive care units (ICUs) that caused by antimicrobial Drug Resistance (AMR) Gram-Negative bacilli (GNB) has become a major public health threat since there is a limited effective treatment. This study is aimed to determine the Prevalence Rate of NCI, and the antibiotic susceptibility pattern of isolates. A cross-sectional study was conducted in six adult ICUs at Al Thawra General hospital, Sana'a, Yemen. A total of 117 admitted patients were included in the study from the period of 1st August to 31st October 2021. A pre-designed questionnaire was used for the collection of socio-demographic and clinical data, various clinical specimens were collected from NCI patients and processed using Vitek 2 automated system to identify the isolates and its susceptibility pattern. Carbapenemase producing was tested by Imipenem-EDTA synergy disc diffusion test according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Data were analyzed using Epi-info version 7.2 statistical software packages (CDC, USA), and the results were presented as descriptive statistics: rates & frequency for categorical variables while, mean ±SD or\medium (minimum --maximum) for quantitative variables. The prevalence of NCI in ICUs was 46%. The most isolates were GNB (88%, 52/59). K pneumoniae was the most prevalent (37%, 19/52) while, P aeruginosa and A baumannii were the most resistant. The resistance for tested antibiotics was 98% (51/52) of isolates; 75% of them showed Extensive Drug Resistance (XDR), and 47% were Carbapenemase producers. However, most AMR-GNB is still susceptible to Polymyxin B and Colistin, the resistance has found to be 10% and 12 % respectively. The high prevalence of AMR-NCI in ICUs calls for an urgent establishment of a stewardship program with strict measures of Infection Prevention Control and regular monitoring of the resistant strains. [ABSTRACT FROM AUTHOR]

Introduction: Nosocomial infectious ventriculitis caused by multidrug-resistant (MDR) Gram-negative bacilli associated with external ventricular drainage (EVD) placement poses a significant mortality burden and hospital costs. Objectives: This study aims to analyze the characteristics, ventriculitis evolution, treatment, and outcomes of patients with ventriculitis due to MDR Gram-negative bacilli associated with EVD placement. Methods: A retrospective cohort study focusing on patients with nosocomial infection caused by MDR Gram-negative bacilli while on EVD was conducted from 2019 to 2022. Medical, laboratory, and microbiological records were collected. The antibiotic resistance of the Gram-negative bacilli isolated in the cerebrospinal fluid (CSF) of patients was analyzed. The risk factors were identified using univariate risk models and were analyzed using survival curves (Cox regression). An adjusted Cox proportional hazards model was also constructed. Results: Among 530 patients with suspected EVD-associated ventriculitis, 64 patients with isolation of Gram-negative bacilli in CSF were included. The estimated mortality was 78.12%. Hemorrhages (intracranial, subarachnoid, and intraventricular) were observed in 69.8% of patients. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequently isolated bacilli. In the univariate analysis, significant risk factors for mortality included arterial hypertension, a Glasgow Coma Scale (GCS) score of _8, invasive mechanical ventilation (IMV) upon hospital admission and during hospitalization, septic shock, and ineffective treatment. The adjusted Cox proportional hazards model revealed that septic shock (HR = 3.3, 95% CI = 1.5-7.2; p = 0.003) and ineffective treatment (HR = 3.2, 1.6-6.5, 0.001) were significant predictors. A high resistance to carbapenems was found for A. baumannii (91.3%) and P. aeruginosa (80.0%). Low resistance to colistin was found for A. baumannii (4.8%) and P. aeruginosa (12.5%). Conclusion: Ineffective treatment was an independent hazard factor for death in patients with ventriculitis caused by MDR Gram-negative bacilli associated with EVD. [ABSTRACT FROM AUTHOR]

Background: The production of metallo-beta-lactamases (MBL) such as VIM (Verona integron-encoded metallo-ß-lactamase), IMP (Imipenem-resistant Pseudomonas) and NDM (New Delhi metallo-ß-lactamase) in Gram-negative bacilli (GNB) resistant to carbapenems is a real concern for clinicians, given the therapeutic impasses involved. However, the existence of resistance genes encoding these enzymes is virtually undocumented in Burkina Faso. Aim: To genotypically demonstrate carbapenem resistance through the production of VIM-type carbapenemases in GNB strains collected at the Centre Hospitalier Universitaire de Tengandogo (CHU-T) and the Hôpital Saint Camille de Ouagadougou (HOSCO) in Burkina Faso. Methods: In this study, the resistance profile of 158 strains of GNB to imipenem, meropenem, ertapenem, doripenem and aztreonam was determined using the disc diffusion method. Resistant strains were analyzed by conventional PCR to detect blaVIM using specific primers. Results: Of 158 GNB strains collected, 91 (57.6%) were resistant to at least one of the carbapenems and/or aztreonam. The highest prevalence of resistant strains was observed in Escherichia coli (E. coli) 45.1% (n=41) and Klebsiella pneumoniae (K. pneumonia) 26.5% (n=24), which are the majority species. The blaVIM gene was detected in only 7 resistant strains (7.7%), including 3.3% (n=3/91) of E. coli, and 1.1% (n=1/91) of each of the species Pseudomonas aeruginosa (P. aeruginosa), Klebsiella oxytoca (K. oxytoca), Proteus mirabilis (P. mirabilis) and Serratia marcescens (S. marcescens). Conclusion: This study established the existence of blaVIM gene, which is involved in the resistance of GNB to carbapenems through the production of VIM-type enzymes at CHU-T and HOSCO in Burkina Faso. [ABSTRACT FROM AUTHOR]

ABSTRACT Rapid microbiological diagnosis of the antibiotic susceptibility of Gram-negative bacilli is a priority in clinical microbiology, especially in cases of bacteremia. The rapid advancement of antimicrobial resistance proposes a challenge for empirical antibiotic therapy and shows the need for fast antibiotic susceptibility diagnostics to guide treatments. The QuickMIC System (Gradientech AB, Uppsala, Sweden) is a recently developed rapid diagnostic tool for antibiotic susceptibility testing. Our study evaluates a rapid phenotypic system (QuickMIC) that provides information on the susceptibility of 12 antibiotics against Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Proteus spp., Citrobacter spp., and Serratia marcescens. A total of 816 antibiotic/microorganism combinations were tested, resulting in eight discrepancies. The concordance between the antibiotics offered by QuickMIC and reference methods (MicroScan WalkAway plus system, Beckman Coulter; Etest (BioMerieux microdilution system (Bruker); Real-time PCR (GeneXpert, Cepheid); and immunochromatography (Biotech) was 99.02%. Time elapsed to obtain a valid minimal inhibitory concentration (MIC) was between 2 and 4 h. The QuickMIC system allows for the early adjustment of antibiotic treatment in these infections. Given the existing limitations of currently available rapid methods, its clinical utility is particularly relevant in the management of P. aeruginosa infections and AmpC-producing Enterobacterales. The use of rapid methods can help diversify antibiotic use and reduce carbapenem consumption.IMPORTANCEThe rapid diagnosis of antibiotic sensitivity in Gram-negative bacilli is of paramount importance in clinical microbiology, particularly in cases of bacteremia. The escalating challenge of antimicrobial resistance underscores the need for expeditious antibiotic susceptibility diagnostics to guide empirical antibiotic therapy effectively. In light of this, we present our study that evaluates the QuickMIC System, a recently developed rapid diagnostic antibiogram. QuickMIC System, offers a novel approach to phenotypic testing, providing information on the activity of 12 antibiotics against key pathogens, including Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Proteus spp., Citrobacter spp., and Serratia marcescens. Our investigation involved testing a total of 816 antibiotic/microorganism combinations. The study demonstrated an impressive 99.02% concordance between the QuickMIC System and the reference methods, with only eight discrepancies observed. The time to actionable minimum inhibitory concentration (MIC) ranged between 2 and 4 h, highlighting the system's efficiency in providing rapid results.

ABSTRACT The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci. A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34–3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18–1.81), biliary (OR 1.84, CI 1.34–2.52) or urinary source (OR 1.86, CI 1.43–2.43), admission period (OR) 1.28, CI 1.18–1.38, and community-acquired infection (OR 0.57, CI 0.39–0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes.IMPORTANCEMultidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts.

Introduction. Despite the efforts made and measures taken to combat antimicrobial resistance, alarming levels of resistance in gram-negative bacteria continue to be reported on a global scale. The antimicrobial resistance mechanisms of these bacteria represent the main cause of therapeutic failures. Material and methods. A retrospective analysis of strains of E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii isolated from patients with invasive infections was conducted for the period 2020-2023. Screening for carbapenemase-producing strains was performed based on sensitivity to antimicrobial agents tested using the Vitek-2 compact automated system. Confirmation of resistance mechanisms was achieved through multiplex PCR molecular biology technique. Results. The analysis of the obtained data indicates high resistance among strains of K. pneumoniae to fluoroquinolones (77.2%), while the majority of E. coli strains were resistant to penicillins (53.5%). Concerningly, non-fermentative bacilli strains also present alarming figures, with over 60.0% of P. aeruginosa strains resistant to penicillins, ceph-alosporins, fluoroquinolones, carbapenems, and over 80.0% of A. baumannii strains resistant to all tested antimicrobial groups. The resistance enzyme OXA-48 was detected in 91.7% of K. pneumoniae strains and 15.6% of E. coli strains, while the blaNDM resistance gene was detected in 15.9% of P. aeruginosa isolates, and the blaOXA-23 gene was identified in 55.2% of A. baumannii isolates. Conclusions. The rapid identification of multi-drug resistant gram-negative bacilli ensures the success of therapy for infections caused by them, and monitoring resistance profiles is an essential step for subsequent actions to combat antimicrobial resistance.

Abstract Background The problem of resistance to beta-lactam antibiotics, which is caused by ESBL and AmpC β-lactamases, is getting worse globally. Infections caused by bacterial isolates harboring these enzymes are difficult to treat with carbapenems being the sole effective treatment option for such infections. The objective of this study was to determine the frequency of ESBLs and AmpC-producing Gram-negative bacilli isolated from clinical specimens and to evaluate the sensitivity of cefepime-tazobactam combination against them. Methods This is an observational cross-sectional study carried out on 100 Gram-negative bacilli at Theodor Bilharz Research Institute Hospital during the period from February 2015 to January 2016. ESBL production was screened by using the disc diffusion test followed by confirmation by the combined disc confirmatory test, the screening for AmpC production was conducted using the cefoxitin disc test, which was subsequently confirmed by the AmpC disc test. Isolates confirmed positive for ESBL and/ or AmpC production were investigated for their susceptibility to antibiotics. Results Among 100 Gram-negative bacilli, 44 isolates were confirmed as ESBL producers by the combined disc confirmatory test out of 56 isolates that tested positive for ESBL production through the disc diffusion test. The presence of AmpC production was assessed using the cefoxitin disc test, 32 isolates were screened to be AmpC producers, and the AmpC disc test confirmed AmpC production in 9 isolates of them. Using the Mast® D68C set, 32 isolates were ESBL producers, 3 were AmpC producers, and 4 isolates were ESBL/AmpC co-producers. The highest sensitivity was to cefepime-tazobactam (91.48%) followed by the carbapenems. Conclusion Cefepime-tazobactam showed remarkable activity against ESBL and/or AmpC-producing Gram-negative bacilli and may be considered as a therapeutic alternative to carbapenems.

Abstract Background Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP. Methods We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events. Results Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17–0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19–3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00–2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03–2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02–2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin. Conclusions This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603

Abstract Introduction Carbapenem-resistant gram-negative bacilli are a worldwide concern because of high morbidity and mortality rates. Additionally, the increasing prevalence of these bacteria is dangerous. To investigate the extent of antimicrobial resistance and prioritize the utility of novel drugs, we evaluated the molecular characteristics and antimicrobial susceptibility profiles of carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii in Ecuador in 2022. Methods Ninety-five clinical isolates of carbapenem non-susceptible gram-negative bacilli were collected from six hospitals in Ecuador. Carbapenem resistance was confirmed with meropenem disk diffusion assays following Clinical Laboratory Standard Institute guidelines. Carbapenemase production was tested using a modified carbapenemase inactivation method. Antimicrobial susceptibility was tested with a disk diffusion assay, the Vitek 2 System, and gradient diffusion strips. Broth microdilution assays were used to assess colistin susceptibility. All the isolates were screened for the bla KPC, bla NDM, bla OXA-48, bla VIM and bla IMP genes. In addition, A. baumannii isolates were screened for the bla OXA-23, bla OXA-58 and bla OXA-24/40 genes. Results Carbapenemase production was observed in 96.84% of the isolates. The bla KPC, bla NDM and bla OXA-48 genes were detected in Enterobacterales, with bla KPC being predominant. The bla VIM gene was detected in P. aeruginosa, and bla OXA-24/40 predominated in A. baumannii. Most of the isolates showed co-resistance to aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. Both ceftazidime/avibactam and meropenem/vaborbactam were active against carbapenem-resistant gram-negative bacilli that produce serin-carbapenemases. Conclusion The epidemiology of carbapenem resistance in Ecuador is dominated by carbapenemase-producing K. pneumoniae harbouring bla KPC. Extensively drug resistant (XDR) P. aeruginosa and A. baumannii were identified, and their identification revealed the urgent need to implement strategies to reduce the dissemination of these strains.

The occurrence of carbapenemases encoding genes in Providencia rettgeri is a critical public health concern since this species has intrinsic resistance to several antimicrobials, including polymyxins. The identification of this multidrug-resistant (MDR) pathogen outside the hospital setting has become increasingly frequent, and raises an alert for the global health agencies, as they indicate a possible spread of such pathogens. Herein, we described three MDR P. rettgeri isolates carrying a diversity of antimicrobial resistance genes (ARGs) isolated from stool samples of swine and bovine in Brazil. Molecular analysis revealed that all isolates belonged to the same clone. The whole genome sequencing (WGS) of a representative isolate (PVR-188) was performed by MiSeq Illumina® platform, while the assembling and annotation was achieved using SPAdes and Prooka, respectively. The WGS analyses indicated the presence of ARGs that confer resistance to β-lactams (blaNDM-1, blaCTX-M-2), quinolones (qnrD1), aminoglycosides (aadA2, aadA1, aph(3′)-Via), phenicol (catB2), sulfonamides (sul1, sul2), and trimethoprim (dfrA12, dfrA1). The presence of three plasmid replicons (Col3M, IncQ1, and IncT) was detected, but no phage sequences were found. The phylogenetic analyses confirmed the genomic relationship of the PVR-188 with P. rettgeri isolates recovered from animals and humans in the USA and Malaysia. In conclusion, we report the occurrence of MDR P. rettgeri clone colonizing the gut microbiota of food-producing animals in Brazil, revealing the spread of this pathogen beyond hospital boundaries.

Background: Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP. Methods: We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events. Results: Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17–0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19–3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00–2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03–2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02–2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin. Conclusions: This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603 [ABSTRACT FROM AUTHOR]

Background: The problem of resistance to beta-lactam antibiotics, which is caused by ESBL and AmpC β-lactamases, is getting worse globally. Infections caused by bacterial isolates harboring these enzymes are difficult to treat with carbapenems being the sole effective treatment option for such infections. The objective of this study was to determine the frequency of ESBLs and AmpC-producing Gram-negative bacilli isolated from clinical specimens and to evaluate the sensitivity of cefepime-tazobactam combination against them. Methods: This is an observational cross-sectional study carried out on 100 Gram-negative bacilli at Theodor Bilharz Research Institute Hospital during the period from February 2015 to January 2016. ESBL production was screened by using the disc diffusion test followed by confirmation by the combined disc confirmatory test, the screening for AmpC production was conducted using the cefoxitin disc test, which was subsequently confirmed by the AmpC disc test. Isolates confirmed positive for ESBL and/ or AmpC production were investigated for their susceptibility to antibiotics. Results: Among 100 Gram-negative bacilli, 44 isolates were confirmed as ESBL producers by the combined disc confirmatory test out of 56 isolates that tested positive for ESBL production through the disc diffusion test. The presence of AmpC production was assessed using the cefoxitin disc test, 32 isolates were screened to be AmpC producers, and the AmpC disc test confirmed AmpC production in 9 isolates of them. Using the Mast® D68C set, 32 isolates were ESBL producers, 3 were AmpC producers, and 4 isolates were ESBL/AmpC co-producers. The highest sensitivity was to cefepime-tazobactam (91.48%) followed by the carbapenems. Conclusion: Cefepime-tazobactam showed remarkable activity against ESBL and/or AmpC-producing Gram-negative bacilli and may be considered as a therapeutic alternative to carbapenems. [ABSTRACT FROM AUTHOR]

Introduction: Carbapenem-resistant gram-negative bacilli are a worldwide concern because of high morbidity and mortality rates. Additionally, the increasing prevalence of these bacteria is dangerous. To investigate the extent of antimicrobial resistance and prioritize the utility of novel drugs, we evaluated the molecular characteristics and antimicrobial susceptibility profiles of carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii in Ecuador in 2022. Methods: Ninety-five clinical isolates of carbapenem non-susceptible gram-negative bacilli were collected from six hospitals in Ecuador. Carbapenem resistance was confirmed with meropenem disk diffusion assays following Clinical Laboratory Standard Institute guidelines. Carbapenemase production was tested using a modified carbapenemase inactivation method. Antimicrobial susceptibility was tested with a disk diffusion assay, the Vitek 2 System, and gradient diffusion strips. Broth microdilution assays were used to assess colistin susceptibility. All the isolates were screened for the blaKPC,blaNDM,blaOXA-48,blaVIM and blaIMP genes. In addition, A. baumannii isolates were screened for the blaOXA-23, blaOXA-58 and blaOXA-24/40 genes. Results: Carbapenemase production was observed in 96.84% of the isolates. The blaKPC, blaNDM and blaOXA-48 genes were detected in Enterobacterales, with blaKPC being predominant. The blaVIM gene was detected in P. aeruginosa, and blaOXA-24/40 predominated in A. baumannii. Most of the isolates showed co-resistance to aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. Both ceftazidime/avibactam and meropenem/vaborbactam were active against carbapenem-resistant gram-negative bacilli that produce serin-carbapenemases. Conclusion: The epidemiology of carbapenem resistance in Ecuador is dominated by carbapenemase-producing K. pneumoniae harbouring blaKPC. Extensively drug resistant (XDR) P. aeruginosa and A. baumannii were identified, and their identification revealed the urgent need to implement strategies to reduce the dissemination of these strains. [ABSTRACT FROM AUTHOR]

Introduction: India has a diabetic population of about 50.8 million, which is expected to increase to 87 million by 2030. Infection worsens the wound condition, delays the healing mechanism, and if appropriate measures are not taken in time, it could lead to systemic infection, septicemia, amputation, or even death. Diabetic foot problems, such as ulcerations, diseases, and gangrene, are the most common cause of hospitalization among diabetic patients. Objective: To determine the microbiological profile and antibiotic susceptibility patterns of organisms isolated from diabetic foot ulcers. Material and methods: A six-month retrospective study was carried out between January 2023 and June 2023 in the Department of Microbiology Government Medical College Anantapur. 250 Wound swabs were collected from diabetic foot ulcer patients and processed per the standard procedure. Antibiotic sensitivity testing was performed using the Kirby Bauer disc diffusion method by CLSI guidelines. Results: Out of 250 samples, 175 (70%) samples yielded growth. Among 175 GNB 124 (70.8%) and GPC 51 (21.6%). Conclusion: In this study, among Gram-negative bacilli, Pseudomonas aeruginosa was the predominant organism 45(36.2%), followed by Escherichia coli 32(25.8%). Among Gram positive cocci, Staphylococcus aureus are 27 (52.9%) out of 27staphylococcus aureus 12 (44.4%) were resistant to Methicillin [MRSA]. The antibiotic profile shows that proper antibiotic usage, if enacted through institutional policy, can reduce morbidity among diabetic foot ulcer patients. [ABSTRACT FROM AUTHOR]

Background: According to the World Health Organization (WHO), bacterial resistance to antibiotics is a global public health challenge, which is also developing in Niger. The aim of this study was to determine the prevalence of antibiotic resistance genes in Gram-negative bacilli isolated from clinical samples in the biological laboratories of two selected health facilities in Niger. Methodology: Clinical bacterial isolates were randomly collected from two biological laboratories of Zinder National Hospital and Niamey General Reference Hospital. These were multi-resistant Gram-negative bacteria that have been routinely isolated from pathological samples of patients. Molecular detection of resistance genes was carried out by polymerase chain reaction (PCR) amplification using specific primers. These include plasmid-mediated AmpC beta lactamase genes (blaCITM, blaDHAM, blaFOXM), 'Cefotaxime-Munich' type beta lactamase genes (blaCTX-M-1, blaCTX-M-2, blaCTX-M-9), KPC-type beta lactamase gene (blaKPC), Oxa-type beta lactamase gene (blaOXA-48), SHV-type beta lactamase gene (blaSHV), TEM-type beta lactamase gene (blaTEM), quinolone resistance genes (qnrA, qnrB, qnrS), and sulfonamide resistance genes (sul1, sul2, sul3). Results: A total of 24 strains of multidrug-resistant Gram-negative bacteria isolated from different clinical samples were analysed. The distribution of the resistance genes detected is as follows; AmpC blaCITM (n=6; 25.0%), AmpC blaDHAM (n=4; 17.0%), AmpC blaFOXM (n=0), blaCTX-M-1 (n=11; 46.0%), blaCTX-M-2 (n=0), blaCTX-M-9 (n=0), blaKPC (n=0), blaOXA-48 (n=2; 8..0%), blaSHV (n=5; 21.0%), blaTEM (n=0), qnrA (n=0), qnrB (n=5; 21.0%), qnrS (n=17; 71.0%), sul1 (n=22; 92.0%), sul2 (n=12; 50.0%), and sul3 (n=0). All isolates tested had at least two resistance genes. Conclusion: The results of this study provide a better understanding of the resistance situation of clinical isolates in Niger. Therefore, it is more than necessary to intensify the detection on a larger number of samples and on a national scale. This will make it possible to assess the true extent of the phenomenon and consequently guide control strategies through a national multisectoral plan. [ABSTRACT FROM AUTHOR]

Imipenem/relebactam (IMR) was approved for patient use in Taiwan in 2023. We evaluated the in vitro susceptibility of recent Gram-negative pathogens collected in Taiwan hospitals to IMR and comparators with a focus on carbapenem-resistant and KPC-carrying non- Morganellaceae Enterobacterales (NME), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). From 2018 to 2021, eight hospitals in Taiwan each collected up to 250 consecutive, aerobic or facultative, Gram-negative pathogens per year from patients with bloodstream, intraabdominal, lower respiratory tract, and urinary tract infections. MICs were determined using Clinical Laboratory Standards Institute (CLSI) broth microdilution. Most isolates that were IMR-, imipenem-, or ceftolozane/tazobactam-nonsusceptible were screened for β-lactamase genes by PCR or whole-genome sequencing. Ninety-eight percent of NME (n = 5063) and 94% of P. aeruginosa (n = 1518) isolates were IMR-susceptible. Percent susceptible values for non-carbapenem β-lactam comparators, including piperacillin/tazobactam, were 68–79% for NME isolates, while percent susceptible values for all β-lactam comparators, including meropenem, were 73–81% for P. aeruginosa. IMR retained activity against 93% of multidrug-resistant (MDR) NME and 70% of MDR P. aeruginosa. Sixty-five percent of carbapenem-resistant NME and 81% of KPC-positive NME (n = 80) were IMR-susceptible. IMR inhibited 70% of CRPA (n = 287). Fifty percent of IMR-nonsusceptible NME tested for β-lactamase carriage had an MBL or OXA-48-like enzyme, whereas most (95%) IMR-nonsusceptible P. aeruginosa examined did not carry acquired β-lactamase genes. Based on our in vitro data, IMR may be a useful option for the treatment of hospitalized patients in Taiwan with infections caused by common Gram-negative pathogens, including carbapenem-resistant NME, KPC-positive NME, and CRPA. [ABSTRACT FROM AUTHOR]

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Introduction: The COVID-19 pandemic increased catheter-related bloodstream infections (C-RBSI), but its subsequent impact has not been adequately described. Our hospital has already depicted the effects of the COVID-19 pandemic in the first wave. However, we still do not know whether C-RBSI rates and aetiology are similar to those described before the COVID-19 pandemic. We aimed to evaluate the impact of the COVID-19 pandemic on the evolution of C-RBSI in a large tertiary teaching hospital two years later. Material and methods: We prospectively collected all confirmed C-RBSI episodes in a clinical microbiology laboratory database by matching blood cultures and catheter tip cultures with the isolation of the same microorganism (s). We compared our C-RBSI incidence rates and aetiology from 2018 to 2023. C-RBSI was defined as bacteremia or fungemia in a patient with clinical manifestations of infection and no other apparent source except the catheter. Results: During the study period, we collected 556 C-RBSI episodes. C-RBSI incidence rate per 1000 admissions each year was as follows: 2018: 2.2; 2019: 1.7; 2020: 3.29; 2021: 2.92; 2022: 2.69. and 2023: 2.01. Mainly, C-RBSI episodes occurring in critical care units each year were, respectively: 2018: 57 (54.8 %), 2019: 38 (45.2 %), 2020: 89 (63.6 %), 2021: 69 (60.5 %), 2022: 58 (50.9 %) and 2023 (61.4 %). The distribution of microorganisms showed an increase in Gram-negative episodes after the pandemic. Conclusion: Our study shows an increase in the incidence rate of C-RBSI during the COVID-19 pandemic, with a discrete decrease after that. C-RBSI episodes were mainly caused by coagulase-negative Staphylococci but with a rise in Gram-negative bacilli.

Background: The ceftazidime-avibactam combination is able to inhibit ESBLs, AmpCs and Class A carbapenemases and has been recommended for the treatment of complicated UTIs and ventilator-associated bacterial pneumonia. Aims: The present study was undertaken to evaluate the in vitro activity of ceftazidime-avibactam and to determine the synergistic activity of aztreonam/ceftazidime-avibactam combination against carbapenem-resistant Gram-negative bacilli. Materials and Methods: Gram-negative isolates that exhibited resistance to at least one of the carbapenems (imipenem or meropenem) by the Kirby–Bauer disc diffusion method were subjected to phenotypic characterisation by the Vitek-2 automated method. Phenotypically confirmed isolates were subjected to ceftazidime/avibactam-aztreonam synergy testing by disc diffusion method. Results: Twenty-two carbapenem-resistant isolates showed a minimum inhibitory concentration of 4–64 μg/mL for imipenem and 8–64 μg/mL for meropenem. Out of 22 carbapenem-resistant isolates, 18 (81.82%) isolates showed resistance to ceftazidime-avibactam and aztreonam, and 2 (9.09%) isolates showed intermediate resistance to aztreonam. Nine (40.91%) isolates showed synergy to ceftazidime-avibactam/aztreonam combination by disc diffusion method. An increase in zone diameter of 5–23 mm and 5–16 mm was observed with the ceftazidime-avibactam/aztreonam combination for Klebsiella pneumoniae and Escherichia coli, respectively, when compared to ceftazidime-avibactam and aztreonam disc tested alone. Out of 21 Enterobacterales studied, 21 (100%) isolates showed resistance to amoxicillin-clavulanate (≥32 μg/mL) and piperacillin-tazobactam (128 μg/mL), 12 (57.14%) isolates showed resistance to gentamicin (≥16 μg/mL), 5 (23.81%) isolates were resistant to amikacin (≥64 μg/mL), 21 (100%) isolates were resistant to ciprofloxacin (≥4 μg/mL), 19 (90.48%) isolates were resistant to cotrimoxazole (≥320 μg/mL), 21 (100%) isolates were resistant to cefepime (≥16 μg/mL) and 6 (28.57%) isolates were resistant to tigecycline (2 μg/mL). Conclusion: In the present study, 42.86% of Enterobacterales isolates showed synergism to the ceftazidime-avibactam/aztreonam combination. The optimal dosing strategy and in vivo efficacy of this combination need to be evaluated.

Introduction. Antimicrobial Resistance (AMR) is one of the most serious threats to global public health, causing over 700 thousand deaths annually. In addition to the social burden, AMR generates high medical costs, and estimating these at the hospital level has been the subject of research in many international studies. Material and methods. A comprehensive study was conducted, encompassing 172 cases of invasive infections recorded in patients hospitalized at the “Timofei Mosneaga” Republican Clinical Hospital, from which strains of antimicrobial-resistant E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa were isolated in the years 2019-2021. Based on data regarding the duration of hospitalization, treatment costs, and expenses for investigations, indicators such as average cost, the median, minimum and maximum values of treatment, including the cost of antibiotics and laboratory analyses, were calculated. Results. The economic impact indicators of AMR at the hospital level include: the duration of hospitalization, the total costs of a treated case, the costs of antibiotics, and the costs of laboratory analyses. In the structure of microorganisms isolated from the patients included in the study, K. pneumoniae predominates, accounting for 44.2%, and the total treatment cost for this organism was the highest at 202731.5 dollars. The maximum duration of hospitalization was recorded in patients from whom A. baumannii was isolated (27.7 days). Conclusions. The resistance of strains isolated from patients has directly contributed to the extension of the hospitalization period. The resistance of A. baumannii and K. pneumoniae species has predominantly led to the increase in the economic burden of AMR.

Background and Aim: Houseflies (Musca domestica) are synanthropic insects that are vectors of a wide range of multidrug-resistant pathogens responsible for infectious diseases. The aim of this study was to detect and characterize multidrug-resistant Enterobacteriaceae carried by houseflies in Bobo-Dioulasso. Materials and Methods: A total of 500 houseflies were captured in hospital and non-hospital environments in the city of Bobo-Dioulasso. For bacteriological analysis, they were divided into 125 batches of five flies each. Multidrug-resistant bacteria isolated on MacConkey agar supplemented with 4 μg/mL cefotaxime were identified on the basis of biochemical characteristics. Antibiotic susceptibility profiles were determined using the agar diffusion method. blaCTX-M resistance genes and quinolone resistance genes (plasmid-mediated quinolone resistance) were detected by conventional polymerase chain reaction. Results: Among 115 bacterial strains obtained, 26 were extended-spectrum beta-lactamase (ESBL)-producing enterobacteria: Escherichia coli (15), Klebsiella pneumoniae (6), Enterobacter cloacae (4), and Morganella morganii (1). Carriers were statistically more important in hospitals (12/26, p = 0.03). No carbapenem-resistance strains were observed. We identified ESBL resistance genes (Cefotaximase Munich; CTX-M group 1) (25/26) and quinolone resistance genes (QnrS) (6/26). Conclusion: Houseflies in the city of Bobo-Dioulasso are vectors for the transmission of multidrug-resistant enterobacteria. There is a need to monitor the associated risks for public health.

Abstract Introduction Shorter courses of antimicrobials have been shown to be non-inferior to longer, “traditional” duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. Methods This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. Planned Outcomes The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. Conclusion The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. Trial Registration ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).

Antimicrobial resistance (AMR) is a critical global issue affecting public and animal health. The overuse of antibiotics in human health, animal production, agriculture, and aquaculture has led to the selection of antibiotic-resistant strains, particularly in Gram-negative bacteria. Mutations and horizontal gene transfer play a significant role in the development of antimicrobial resistance, leading to the reduced efficacy of current antibiotics. Today, AMR in bacteria and antibiotic-resistance genes (ARGs) are increasingly recognized in multiple environmental sources, including recreational and irrigation waters. This study aims to identify Gram-negative bacteria from surface aquatic reservoirs in southern Chile and assess their susceptibility to clinically relevant antibiotics. Water samples were collected from four lakes, five rivers, one waterfall, and one watershed in southern Chile to isolate environmental Gram-negative bacilli (GNB). API-20E and MALDI–TOF were employed for bacterial identification. Kirby–Bauer disc diffusion tests and multiplex PCR were performed to determine their susceptibility profile. A total of 26 GNB strains were isolated from environmental water samples, predominantly belonging to the Pseudomonas (n = 9) and Acinetobacter (n = 7) genera. Among these strains, 96.2% were resistant to ampicillin and cefazoline, while 26.9% and 34.6% showed resistance to ceftazidime and cefepime, respectively. Additionally, 38.5% exhibited resistance to colistin. Two Enterobacter cloacae strains obtained from Cachapoal River (sixth region) and Villarrica Lake (ninth region), respectively, presented a multidrug-resistant (MDR) phenotype and carried at least two extended-spectrum β-lactamase (ESBL) genes. Thus, antibiotic-resistant GNB and ARGs were found in natural water reservoirs, raising concerns about the dissemination of resistance determinants among potentially pathogenic bacteria in environmental microbial communities.

Background: Houseflies (Musca domestica) are synanthropic insects that are vectors of a wide range of multidrug-resistant pathogens responsible for infectious diseases. The aim of this study was to detect and characterize multidrug-resistant Enterobacteriaceae carried by houseflies in Bobo-Dioulasso. Materials and Methods: A total of 500 houseflies were captured in hospital and non-hospital environments in the city of Bobo-Dioulasso. For bacteriological analysis, they were divided into 125 batches of five flies each. Multidrug-resistant bacteria isolated on MacConkey agar supplemented with 4 µg/mL cefotaxime were identified on the basis of biochemical characteristics. Antibiotic susceptibility profiles were determined using the agar diffusion method. blaCTX-M resistance genes and quinolone resistance genes (plasmid-mediated quinolone resistance) were detected by conventional polymerase chain reaction. Results: Among 115 bacterial strains obtained, 26 were extended-spectrum beta-lactamase (ESBL)-producing enterobacteria: Escherichia coli (15), Klebsiella pneumoniae (6), Enterobacter cloacae (4), and Morganella morganii (1). Carriers were statistically more important in hospitals (12/26, p = 0.03). No carbapenem-resistance strains were observed. We identified ESBL resistance genes (Cefotaximase Munich; CTX-M group 1) (25/26) and quinolone resistance genes (QnrS) (6/26). Conclusion: Houseflies in the city of Bobo-Dioulasso are vectors for the transmission of multidrug-resistant enterobacteria. There is a need to monitor the associated risks for public health. [ABSTRACT FROM AUTHOR]

Aquaculture has been recognized as a hotspot for the emergence and spread of antimicrobial resistance genes conferring resistance to clinically important antibiotics. This review gives insights into studies investigating the prevalence of colistin and carbapenem resistance (CCR) among Gram-negative bacilli in aquaculture. Overall, a high incidence of CCR has been reported in aquatic farms in several countries, with CCR being more prevalent among opportunistic human pathogens such as Acinetobacter nosocomialis, Shewanella algae, Photobacterium damselae, Vibrio spp. Aeromonas spp. as well as members of Enterobacteriaceae family. A high proportion of isolates in these studies exhibited wide-spectrum profiles of antimicrobial resistance, highlighting their multidrug-resistance properties (MDR). Several mobile colistin resistance genes (including, mcr-1, mcr-1.1, mcr-2, mcr-2.1, mcr-3, mcr-3.1, mcr-4.1, mcr-4.3, mcr-5.1, mcr-6.1, mcr-7.1, mcr-8.1 , and mcr-10.1) and carbapenemase encoding genes (in c luding, bla OXA-48, bla OXA-55 , bla NDM, bla KPC, bla IMI, bla AIM, bla VIM, and bla IMP) have been detected in aquatic farms in different countries. The majority of these were carried on MDR Incompatibility (Inc) plasmids including IncA/C, and IncX4, which have been associated with a wide host range of different sources. Thus, there is a risk for the possible spread of resistance genes between fish, their environments, and humans. These findings highlight the need to monitor and regulate the usage of antimicrobials in aquaculture. A multisectoral and transdisciplinary (One Health) approach is urgently needed to reduce the spread of resistant bacteria and/or resistance genes originating in aquaculture and avoid their global reach. [ABSTRACT FROM AUTHOR]

Introduction: Shorter courses of antimicrobials have been shown to be non-inferior to longer, "traditional" duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. Methods: This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. Planned Outcomes: The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. Conclusion: The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. Trial Registration: ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE). [ABSTRACT FROM AUTHOR]

Background: Gram-negative bacilli are one of the most common causes of various infections in clinical. The emergence and global spread of multi-drug resistant gram-negative bacilli has become a major challenge in the global public health field. Methods: A total of 51,189 non-repetitive strains of gram-negative bacilli were isolated in clinical settings. The antimicrobial susceptibility testing was conducted by using the automated VITEK 2 compact system and the matched AST susceptibility test card, complemented by the disk diffusion method. The antimicrobial susceptibility results were interpreted by CLSI. Rates of MDR and XDR in Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa were investigated. Used the chi-square test to determine whether the antimicrobial resistance rates of four major gram-negative bacilli isolated from ICU and non-ICU department have statistical differences. Results: Escherichia coli (31.4%), Klebsiella spp. (21.2%), Acinetobacter spp. (13.8%), and P. aeruginosa (11.0%) were the most frequently isolated gramnegative bacilli. Escherichia coli was the top one organism isolated from urinary tract (68.4%), bloodstream (39.9%), body fluid (33.2%), wound and pus (37%), except for respiratory tract (8.8%). Whereas Acinetobacter baumannii and K. pneumoniae were the major isolated organisms from respiratory tract. Acinetobacter baumannii showed high resistance to fluoroquinolones, β-lactam/ β-lactamase inhibitor combinations class, ceftazidime, cefepime, imipenem, and meropenem, the resistance rates reached more than 70%. Ceftazidime showed a lower resistance rate to E. coli than ceftriaxone. For E. coli, fluoroquinolones showed a high resistance rate (ciprofloxacin 61.36% and levofloxacin 53.97%), whereas amikacin, carbapenems exhibited a lower resistance rate fluctuating at 2%. Acinetobacter baumannii and K. pneumoniae showed rapid increases in carbapenem resistance whereas E. coli had the lowest resistance rate and remain stable at 2%. Acinetobacter baumannii exhibited the highest rate of MDR and XDR, reaching 60–80 and 45–55%, respectively. Compared to non-ICU departments, the resistance rates of four major gram-negative bacilli in the ICU department were much higher and the differences were statistically significant (p <  0.05). Conclusion: Amikacin, carbapenems, and piperacillin/tazobactam exhibited relatively high sensitivity, whereas fluoroquinolones showed high resistance rate whether they can be the first-line antimicrobials for empirical treatment of UTI should take more consideration. The gram-negative bacilli in ICU were more resistance than that in non-ICU. These findings are helpful for clinicians using antimicrobials reasonably. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a critical global issue affecting public and animal health. The overuse of antibiotics in human health, animal production, agriculture, and aquaculture has led to the selection of antibiotic-resistant strains, particularly in Gram-negative bacteria. Mutations and horizontal gene transfer play a significant role in the development of antimicrobial resistance, leading to the reduced efficacy of current antibiotics. Today, AMR in bacteria and antibiotic-resistance genes (ARGs) are increasingly recognized in multiple environmental sources, including recreational and irrigation waters. This study aims to identify Gram-negative bacteria from surface aquatic reservoirs in southern Chile and assess their susceptibility to clinically relevant antibiotics. Water samples were collected from four lakes, five rivers, one waterfall, and one watershed in southern Chile to isolate environmental Gram-negative bacilli (GNB). API-20E and MALDI–TOF were employed for bacterial identification. Kirby–Bauer disc diffusion tests and multiplex PCR were performed to determine their susceptibility profile. A total of 26 GNB strains were isolated from environmental water samples, predominantly belonging to the Pseudomonas (n = 9) and Acinetobacter (n = 7) genera. Among these strains, 96.2% were resistant to ampicillin and cefazoline, while 26.9% and 34.6% showed resistance to ceftazidime and cefepime, respectively. Additionally, 38.5% exhibited resistance to colistin. Two Enterobacter cloacae strains obtained from Cachapoal River (sixth region) and Villarrica Lake (ninth region), respectively, presented a multidrug-resistant (MDR) phenotype and carried at least two extended-spectrum β-lactamase (ESBL) genes. Thus, antibiotic-resistant GNB and ARGs were found in natural water reservoirs, raising concerns about the dissemination of resistance determinants among potentially pathogenic bacteria in environmental microbial communities. [ABSTRACT FROM AUTHOR]

Introduction: Recent reports have described the increasing predominance of Gram-negative organisms among invasive bacterial infections affecting preterm infants. This changing pattern of infections is concerning due to the spread of antibiotic resistance among Gram-negatives. Method: We conducted a single-centre, retrospective cohort study involving very-low-birthweight (VLBW) (<1500 grams) infants born <32 weeks gestation, with culture-proven infections (blood, urine, cerebrospinal fluid [CSF]) in the neonatal intensive care unit from 1 January 2005 to 31 October 2017. Results: A total of 278 out of 2431 (11.4%) VLBW infants born <32 weeks gestation developed 334 infections, i.e. 52 (15.6%) early-onset infections (EOIs) and 282 (84.4%) late-onset infections (LOIs). The overall incidence decreased from 247 to 68 infections per 1000 infants over the study period, corresponding to reductions in LOI (211 to 62 infections per 1000 infants). A total of 378 bacteria were isolated, i.e. Gram-negatives accounted for 70.9% (45 of 59 [76.3%] EOI; 223 of 319 [69.9%] LOI). Specific resistant organisms were noted, i.e. Methicillin-resistant Staphylococcus aureus (8 of 21 S. aureus infections [38.1%]); Cephalosporin-resistant Klebsiella (18 of 62 isolates [29.0%]) and multidrug-resistant [MDR] Acinetobacter (10 of 27 isolates [37.0%]). MDR organisms accounted for 85 of 195 (43.6%) Gramnegative infections from the bloodstream and CSF. Based on laboratory susceptibility testing, only 63.5% and 49.3% of infecting bacteria isolated in blood were susceptible to empiric antibiotic regimens used for suspected EOI and LOI, respectively. Conclusion: Gram-negative bacteria are the predominant causative organisms for EOI and LOI and are frequently MDR. Understanding the pattern of antimicrobial resistance is important in providing appropriate empiric coverage for neonatal infections. [ABSTRACT FROM AUTHOR]

IntroductionNosocomial infectious ventriculitis caused by multidrug-resistant (MDR) Gram-negative bacilli associated with external ventricular drainage (EVD) placement poses a significant mortality burden and hospital costs.ObjectivesThis study aims to analyze the characteristics, ventriculitis evolution, treatment, and outcomes of patients with ventriculitis due to MDR Gram-negative bacilli associated with EVD placement.MethodsA retrospective cohort study focusing on patients with nosocomial infection caused by MDR Gram-negative bacilli while on EVD was conducted from 2019 to 2022. Medical, laboratory, and microbiological records were collected. The antibiotic resistance of the Gram-negative bacilli isolated in the cerebrospinal fluid (CSF) of patients was analyzed. The risk factors were identified using univariate risk models and were analyzed using survival curves (Cox regression). An adjusted Cox proportional hazards model was also constructed.ResultsAmong 530 patients with suspected EVD-associated ventriculitis, 64 patients with isolation of Gram-negative bacilli in CSF were included. The estimated mortality was 78.12%. Hemorrhages (intracranial, subarachnoid, and intraventricular) were observed in 69.8% of patients. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequently isolated bacilli. In the univariate analysis, significant risk factors for mortality included arterial hypertension, a Glasgow Coma Scale (GCS) score of ≤ 8, invasive mechanical ventilation (IMV) upon hospital admission and during hospitalization, septic shock, and ineffective treatment. The adjusted Cox proportional hazards model revealed that septic shock (HR = 3.3, 95% CI = 1.5–7.2; p = 0.003) and ineffective treatment (HR = 3.2, 1.6–6.5, 0.001) were significant predictors. A high resistance to carbapenems was found for A. baumannii (91.3%) and P. aeruginosa (80.0%). Low resistance to colistin was found for A. baumannii (4.8%) and P. aeruginosa (12.5%).ConclusionIneffective treatment was an independent hazard factor for death in patients with ventriculitis caused by MDR Gram-negative bacilli associated with EVD.

Abstract Background Colonization of the oropharynx with gram-negative bacilli (GNB) is considered a negative prognostic factor in immunocompromised individuals. Hemato-oncologic patients represent a high-risk group due to their immunodeficiencies and associated treatments. This study aimed to determine the rates of oral colonization by GNB, associated factors, and clinical outcomes in patients with hematologic malignancies and solid tumors compared with healthy subjects. Methods We conducted a comparative study of hemato-oncologic patients and healthy subjects from August to October 2022. Swabs were taken from the oral cavity; specimens with GNB were identified and tested for antimicrobial susceptibility. Results We included 206 participants (103 hemato-oncologic patients and 103 healthy subjects). Hemato-oncologic patients had higher rates of oral colonization by GNB (34% vs. 17%, P = 0.007) and GNB resistant to third-generation cephalosporins (11.6% vs. 0%, P

ABSTRACT: Objectives: The aim of this study was to estimate carbapenem resistance in Pseudomonas aeruginosa and Enterobacterales isolated from infected patients in intensive care unit (ICU) and non-ICU hospital wards in Hong Kong. Methods: Isolates of Pseudomonas aeruginosa (ICU, n = 35; non-ICU, n = 264) and Enterobacterales (ICU, n = 129; non-ICU, n = 1390) were collected in four Hong Kong hospitals in 2017–2020. Clinical and Laboratory Standards Institute broth microdilution minimum inhibitory concentrations (MICs) were interpreted according to Clinical and Laboratory Standards Institute 2021 M100 breakpoints. β-lactamase genes were identified in imipenem-, imipenem/relebactam-, and ceftolozane/tazobactam-nonsusceptible isolates. Results: Ceftolozane/tazobactam demonstrated potent in vitro activity against both P. aeruginosa (ICU, 88.6%; non-ICU, 98.5%) and Enterobacterales (96.1%; 97.1%). Percent susceptible values for P. aeruginosa isolates from ICU and non-ICU patients, respectively, were as follows: meropenem (ICU, 74.3%; non-ICU, 84.1%) and imipenem (68.6%; 73.1%). Only 1 of 77 isolates tested for β-lactamase genes carried a carbapenemase (VIM-2). Percent susceptible values for Enterobacterales isolates from ICU and non-ICU patients were as follows: meropenem (100%; 99.4%), ertapenem (100%; 98.0%), and imipenem (88.4%; 88.6%). A total of 62 Enterobacterales isolates were tested for β-lactamase genes. Only three isolates carried a carbapenemase gene; two (both Escherichia coli) were metallo-β-lactamase-positive (both NDM-5), and one (Klebsiella pneumoniae) was OXA-48-like-positive. Conclusions: Carbapenem-nonsusceptible isolates of P. aeruginosa were common (>15% of isolates). P. aeruginosa percent susceptible values for ceftolozane/tazobactam (97.3% susceptible overall) were ≥14% higher than those for carbapenems in both ICU and non-ICU isolates. Carbapenemases were rare among both P. aeruginosa (one isolate) and Enterobacterales (three isolates). Most Enterobacterales isolates tested from ICU and non-ICU patients in Hong Kong hospitals in 2017–2020 were susceptible to meropenem and ertapenem (≥98%); imipenem was less active (89% susceptible).

ABSTRACT: Objectives: Apramycin is an aminoglycoside (AG) with a unique structure that is little affected by plasmid-mediated mechanisms of AG resistance, including most AG-modifying enzymes and 16S rRNA methyltransferases (16S-RMTases). We evaluate the activity of apramycin against a collection of 16S-RMTase-producing isolates, including Enterobacterales, non-fermenting bacteria, and carbapenemase producers. Methods: In total, 164 non-duplicate 16S-RMTase-producing isolates, including 84 Enterobacterales, 53 Acinetobacter baumannii and 27 Pseudomonas aeruginosa isolates, were included in the study. Whole-genome sequencing (WGS) was performed on all isolates with Illumina technology. The minimum inhibitory concentration (MIC) of apramycin was determined by broth microdilution with customized Sensititre plates (Thermo Fisher Scientific, Dardilly, France). Results: We found that 95% (156/164) of the 16S-RMTase-producing isolates were susceptible to apramycin, with a MIC50 of 4 mg/L and a MIC90 of 16 mg/L, respectively. Resistance rates were higher in P. aeruginosa (11%) than in A. baumannii (4%) or Enterobacterales (4%) (P < 0.0001 for each comparison). Eight isolates were resistant to apramycin, including one isolate with an MIC >64 mg/L due to the acquisition of the aac(3)-IV gene. The genetic environment of the aac(3)-IV gene was similar to that in the pAH01–4 plasmid of an Escherichia coli isolate from chicken in China. Conclusion: Resistance to apramycin remains rare in 16S-RMTase-producing isolates. Apramycin may, therefore, be an interesting alternative treatment for infections caused by 16S-RMTase and carbapenemase producers.

ABSTRACT: Background: Relebactam, previously known as MK-7655, is currently being tested in combination with imipenem as a class A and class C β-lactamase inhibitor, including KPC from Klebsiella pneumoniae. Objective: The objective of the current study was to evaluate the activity of imipenem/relebactam against gram-negative bacilli. Methods: After applying exclusion and inclusion criteria, 72 articles with full texts that describe the prevalence of imipenem/relebactam resistance were chosen for the meta-analysis and systematic review. Articles published between January 2015 and February 2023 were surveyed. The systematic literature search was conducted in PubMed, Web of Science, Google Scholar, and Scopus. Results: The pooled estimation of 282,621 sample isolates revealed that the prevalence rate of imipenem/relebactam resistance is roughly 14.6% (95% CI, 0.116%–0.182%). Conclusions: The findings of this analysis show that imipenem/relebactam resistance is rare in the majority of developed countries. Given that relebactam has proven to restore the activity of imipenem against current clinical isolates, further research into imipenem/relebactam is necessary.

Background: The aim of this study was to determine the differences in the incidence, epidemiology, clinical characteristics and risk factors of infections in living donor kidney transplant recipients using robotic-assisted kidney transplantation (RAKT) and open approach. Methods: We conducted a retrospective observational study from January 2016 to December 2019. For the risk factor analysis, a matched case–control study (1:1 ratio) was performed (robotic vs open). Control subjects were matched for living donor and time of transplantation. The data included de novo immunosuppressive regimen, delayed graft function, urological complications, acute allograft rejection and incidence, clinical features, microbiological findings and outcomes of infections. Results: Ninety-four RAKT and 84 controls were included. There were no differences between groups in terms of age, gender, BMI, median days of hospitalization, immunosuppressive regimen, need for surgical urologic procedures post-transplantation, presence of urinary leak or acute allograft rejection. Thirty-five percent of all recipients analyzed presented an infection, mostly asymptomatic bacteriuria (49%), symptomatic urinary tract infection (31%) and surgical site infection (10%). Pseudomonas aeruginosa was the most frequent isolated microorganism in 67%, followed by E. coli (20%), Enterococcus faecalis (17%) and Klebsiella pneumoniae (10%). Eight percent of the microorganisms were multidrug resistant. The open kidney transplantation group presented more infections compared to RAKT (43 vs 27%, p = 0.04). After multivariate analysis, need for surgical urologic procedure post-transplantation (OR 6.2, 95% CI 1.1–35), BMI ≥ 30 (OR 3.6, 95% CI 1.5–9) and acute allograft rejection (OR 3.2, 95% CI 1.2–8.5) were associated with infection, whereas RAKT (OR 0.5, 95% CI 0.2–0.9) and the use of JJ catheter (OR 0.36, 95% CI 0.17–0.72) were protective factors. Conclusions: Infection is a frequent event in patients receiving a living donor kidney transplant. Acute allograft rejection, need for surgical urologic procedure post-transplantation and BMI were associated with infection, whereas robotic surgery was a protective factor in living donor kidney transplantation. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is poorly characterised and may be emerging as a consequence of medical progress. We performed an observational retrospective case-control study. Cases were non-HACEK GNB IE, definite or possible (modified Duke criteria), diagnosed in adults between 2007 and 2020 in six French referral hospitals. Two controls were included for each case (IE due to other bacteria, matched by sites and diagnosis date). Non-HACEK GNB were identified in 2.4% (77/3230) of all IE during the study period, with a mean age of 69.2 ± 14.6 years, and a large male predominance (53/77, 69%). Primary pathogens were Escherichia coli (n = 33), Klebsiella sp. (n = 12) and Serratia marcescens (n = 9), including eight (10%) multidrug-resistant GNB. Compared to controls (n = 154: 43% Streptococcus sp., 41% Staphylococcus sp. and 12% Enterococcus sp.), non-HACEK GNB IE were independently associated with intravenous drug use (IVDU, 8% vs. 2%, p =.003), active neoplasia (15% vs. 6%, p =.009), haemodialysis (9% vs. 3%, p =.007) and healthcare-associated IE (36% vs. 18%, p =.002). Urinary tract was the main source of infection (n = 25, 33%) and recent invasive procedures were reported in 29% of cases. Non-HACEK GNB IE were at lower risk of embolism (31% vs. 47%, p =.002). One-year mortality was high (n = 28, 36%). Comorbidities, particularly malignant hemopathy and cirrhosis, were associated with increased risk of death. Non-HACEK GNB are rarely responsible for IE, mostly as healthcare-associated IE in patients with complex comorbidities (end-stage renal disease, neoplasia), or in IVDUs. [ABSTRACT FROM AUTHOR]

Introduction: The spread of multidrug-resistant bacteria, particularly carbapenem-resistant Gram-negative bacilli (CR-GNB), has become a serious challenge for clinicians due to limited therapeutic options. The aim of the study was to investigate the prevalence of carbapenemase production among clinical isolates recovered from 352 samples collected in Tebessa hospital, Algeria. Methodology: Bacterial isolates were identified by 16S RNA gene sequencing and susceptibility to antibiotics was determined by disk diffusion method. Carbapenem-resistant isolates were screened for carbapenemase production using modified carba Nordmann-Poirel test, modified Hodge test and imipenem-EDTA combined disc test. Extended-spectrum ß-lactamases (ESBL) were detected using double-disk synergy test. Molecular characterization of carbapenemases and ESBL genes was performed by polymerase chain reaction (PCR) and sequencing. Results: A total of 85 Gram-negative bacilli isolates were recovered mainly from urine samples and were identified as: Klebsiella pneumoniae (17.65%), Serratia odorifera (15.29%), Escherichia coli (12.94%), Raoultella ornithinolytica, Enterobacter cloacae (11.76%), Serratia marcescens (10.59%), Morganella morganii (7.06%), Proteus mirabilis (5.88%), Acinetobacter baumannii (4.70%) and Pseudomonas aeruginosa (2.35%). All strains were resistant or intermediate to imipenem and/or ertapenem. ESBL, carbapenemase and metallo-betalactamases (MBL) phenotypes were detected in 19 (22.35%), 9 (10.59%) and 2 (2.35%) GNB isolates, respectively. PCR results in nine carbapenemase-producing GNB strains chosen showed the presence of one to four carbapenemase genes (blaGES, blaSME, blaNDM-1, blaVIM, blaGIM, blaSPM, blaOXA-48) in four strains; however, seven strains had at least one ESBL gene (blaTEM-1, blaCTXM-15, blaSHV). Conclusions: In this study, we report the first incidence of blaNDM-1 gene in Enterobacter cloacae isolated from urine sample in Algeria. [ABSTRACT FROM AUTHOR]

We examined the in vitro susceptibility of meropenem-nonsusceptible Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex isolates from five consecutive annual SIDERO-WT surveillance studies (2014–2019) to cefiderocol and comparator agents in the context of their carbapenemase carriage. 1,003 Enterobacterales, 1,758 P. aeruginosa, and 2,809 A. baumannii complex isolates from North America and Europe that were meropenem nonsusceptible (CLSI M100, 2022) were molecularly characterized for β-lactamase content by PCR followed by Sanger sequencing or by whole genome sequencing. Among Enterobacterales, 91.5% of metallo-β-lactamase (MBL)–producing, 98.4% of KPC-producing, 97.3% of OXA-48 group–producing, and 98.7% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among P. aeruginosa, 100% of MBL-producing, 100% of GES carbapenemase-producing, and 99.8% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Among A. baumannii complex, 60.0% of MBL-producing, 95.6% of OXA-23 group-producing, 89.5% of OXA-24 group-producing, 100% of OXA-58 group-producing, and 95.5% of carbapenemase-negative, meropenem-nonsusceptible isolates were cefiderocol susceptible (MIC ≤4 mg/L). Cefiderocol was inactive against A. baumannii complex isolates carrying a PER or VEB β-lactamase (n = 103; 15.5% susceptible). Ceftazidime–avibactam and ceftolozane–tazobactam were inactive against MBL-carrying and A. baumannii complex isolates; ceftolozane–tazobactam was also inactive against serine carbapenemase–carrying Enterobacterales and P. aeruginosa. In summary, cefiderocol was highly active in vitro against Gram-negative isolates carrying MBLs and serine carbapenemases, as well as carbapenemase-negative, meropenem-nonsusceptible isolates. [ABSTRACT FROM AUTHOR]