Search Results (54)

Antimicrobial resistance (AMR) is a global health threat, increasing morbidity, mortality, and healthcare costs. Multi-drug resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae) cause most hospital-acquired infections. Local data on their resistance profiles remain limited in low-income settings. This study assessed the prevalence and resistance patterns of ESKAPE pathogens isolated from clinical specimens at Rwanda Military Referral and Teaching Hospital. A descriptive cross-sectional study was conducted from June 2022 to January 2023. ESKAPE isolates were identified and tested for antimicrobial susceptibility using the BD Phoenix M50 System. Data on sample type, ward, and demographics were analyzed. Of 744 bacterial findings, 207 (30%) were ESKAPE isolates. After excluding duplicates and non-recovered isolates, 156 were identified as ESKAPE. K. pneumoniae was most common (41%), followed by S. aureus (27%), A. baumannii (13%), P. aeruginosa (11%), and E. cloacae (8%); no E. faecium was detected. Among Gram-negatives, 63% were resistant to third-generation cephalosporins and 32% to carbapenems, with A. baumannii showing highest resistance (85% and 75%). Methicillin-Resistance in Staphylococcus aureus (MRSA) was 7%. This first hospital-based study in Rwanda shows high cephalosporin and carbapenem resistance, highlighting the need to strengthen diagnostics and stewardship. Full article

Carbapenem-resistant Gram-negative (CR-GN) pathogens pose a critical threat to patient outcomes in high-dependency and intensive care environments. This study aimed to delineate species prevalence, antimicrobial resistance phenotypes, carbapenemase genotypes, and clinical–environmental transmission dynamics across critical-care units. Cross-sectional surveillance was conducted in six ICUs and HDUs of a tertiary-care hospital in Karachi, Pakistan. We identified predominant species, quantified resistance patterns, and detected carbapenemase genes using PCR, exclusively on meropenem-resistant isolates. Network analysis highlighted high-centrality contamination hubs across ICUs and HDUs. Acinetobacter baumannii (36.7%) and Klebsiella pneumoniae (33.9%) were predominant, with 58% originating from environmental reservoirs. Meropenem non-susceptibility was 55% (60/109), and colistin non-susceptibility was 68.6% (35/51), based on standardized CLSI testing. ICU isolates exhibited significantly higher meropenem resistance than HDU isolates. Among carbapenem-resistant isolates, blaOXA-48-like (52.8%) and blaNDM (25%) were most prevalent. Network topology revealed ICU1 and HDU2 as high-centrality transmission nodes. These findings highlight pervasive environmental colonization and heightened antimicrobial pressure in ICUs, necessitating reinforced decontamination protocols, antimicrobial stewardship, and continuous molecular surveillance. This study provides the first integrated clinical–environmental surveillance of MDR Gram-negative bacteria in Pakistan, revealing that over half of isolates originated from surfaces and that network-based mapping can pinpoint contamination hubs driving hospital transmission. Full article

Introduction: Eravacycline is a new fluorocycline antibiotic with a broad spectrum of antimicrobial activity approved for the treatment of patients with complicated intra-abdominal infections. This systematic review aimed to evaluate the published data on the resistance of Gram-negative bacterial isolates to eravacycline. Methods: We identified relevant publications by systematically searching Embase, PubMed, Scopus, and Web of Science from their inception to 29 August 2025. Published antimicrobial resistance breakpoints of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the US Food and Drug Administration (FDA) were used. Results: Data on 59,922 Gram-negative bacterial clinical isolates were retrieved from 68 articles after the screening of 283 potentially relevant studies. The resistance of consecutive (non-selected) Escherichia coli ranged from 0.9% to 9.6%. The MIC₅₀ values of eravacycline were ≤0.5 mg/L for Acinetobacter baumannii isolates, including carbapenem-resistant A. baumannii, in the majority of studies. The proportions of resistance were higher among other lactose non-fermenting Gram-negative bacterial isolates, especially Pseudomonas aeruginosa, as well as among selected E. coli with advanced patterns of antimicrobial resistance. Conclusions: The evaluated data support the adequate antimicrobial activity of eravacycline against most Gram-negative bacterial clinical isolates. However, in vitro antimicrobial susceptibility testing and modern molecular diagnostic tests, including those that examine mechanisms of resistance, are helpful for the appropriate use of eravacycline in clinical practice. Full article

Introduction: Due to the limited therapeutic options for patients with Acinetobacter baumannii complex infections, a new combination antimicrobial agent, sulbactam–durlobactam, has been developed. In this systematic review, we evaluated the available data on the resistance of A. baumannii complex clinical isolates to sulbactam–durlobactam. Methods: We performed a thorough search of four databases for relevant studies. The Clinical and Laboratory Standards Institute (CLSI) sulbactam–durlobactam breakpoint for A. baumannii complex susceptibility was used (MIC value ≤4 mg/L). Data on the presence of genes of various β-lactamases were also analyzed. Results: From 182 identified articles, 84 were thoroughly screened. Data extraction was performed on 20 articles (published 2017–2025) reporting on a total of 10,412 A. baumannii complex clinical isolates. Among the various β-lactamases genes present, the OXA subvariants OXA-23/OXA-23-like were the most common (in 561 isolates). The proportions of non-selected (consecutive) A. baumannii isolates found to be resistant to sulbactam–durlobactam were 1.2%, 1.2%, and 4.6% in the three studies, and with non-susceptibility (resistance and intermediate resistance) were 2%, 2.1%, and 4.6% in three other studies. Non-susceptibility was very rare among A. calcoaceticus, A. nosocomialis, and A. pittii isolates (0%, 0.3%, and 0.6%, respectively). The proportion of carbapenem-resistant A. baumannii isolates with resistance was 0–5.2%. The proportion of A. baumannii isolates selected for their reduced susceptibility profile (including reduced susceptibility to cefiderocol) with resistance was 1.4–27.3%. Discussion: The low proportion of sulbactam–durlobactam resistance among A. baumannii complex isolates supports the consideration of the use of this new antibiotic for its approved indications. Full article

Background/Objectives: In this proof-of-concept study, the objective was to evaluate the phenotypic CarbaLux combination rapid test in terms of guiding the therapy of infections caused by multidrug-resistant Gram-negative bacteria with carbapenemase inhibitors and carbapenems, and to compare its results and practicability with standard diagnostic methods. Methods: In the classical CarbaLux test, a fluorescent carbapenem serves as a UV–visible diagnostic surrogate for clinically used carbapenem antibiotics. When exposed to extracted carbapenemases from bacterial colony growth on agar plates, fluorescence rapidly disappears, showing whether monotherapy with carbapenems is possible or must be rejected. It was expected that a specific inhibitor that protects imipenem or meropenem from enzymatic deactivation during antibacterial therapy would perform the same in vitro with fluorescent carbapenem and preserve its fluorescence. The new additional CarbaLux combination test is used if the classic test is positive for carbapenemases: a classic test tube pre-dosed with fluorescent carbapenem is spiked with cloxacillin; with recently launched carbapenemase inhibitors, e.g., avibactam, relebactam, zidebactam, nacubactam, or vaborbactam; or with picolinic acid. Fourteen Enterobacterales and six Acinetobacter baumannii isolates were analyzed. Results: At fixed concentrations, the new inhibitors protected fluorescent carbapenem from bacterial KPC-mediated inactivation and partially from AmpC beta-lactamase-mediated inactivation. In addition, avibactam also effectively inhibited OXA-48-like enzymes. Cloxacillin selectively inhibited AmpC beta-lactamases extracted from Enterobacter complex species. Non-therapeutic picolinic acid was specific for metallo-beta-lactamases and thus identified infections by pathogens that cannot be treated with carbapenems alone or in combination. Conclusions: Inhibitor/fluorescent carbapenem mixtures corresponding to therapeutic inhibitor/carbapenem combinations allow us to visualize the efficacy of carbapenemase inhibitors. The in vitro results are consistent with clinical experience regarding combination therapy. Enzymatic assays provide a rapid yes/no answer for carbapenem mono- or combination therapy and offer several advantages over current carbapenemase testing methods. In contrast to PCR and lateral flow tests, which only target a selection of carbapenemases, enzymatic assays work by employing a reproducible phenotypic mechanism. They are simpler, broader in scope, and more cost-effective; they can also detect antimicrobial heteroresistance or AmpC beta-lactamase hyperproduction, which is normally undetected when performing automated antibiotic susceptibility testing. The new tests are suitable for clinical diagnosis, public health purposes, and infection control. Full article

Antimicrobial resistance (AMR) remains a public health problem in European Union countries, and elderly patients represent a vulnerable category due to aging and its associated risk factors. In this research, we investigated the trend of the antimicrobial resistance pattern of Gram-negative pathogens isolated in samples collected from elderly patients (over 65 years) hospitalized in the intensive care unit (ICU) between 2022 and 2024. A total of 2510 samples, including blood, tracheal aspirate, sputum, urine, pus/wound swabs, exudates, intravascular catheters, cerebrospinal fluid, and sterile fluids, were collected from 1864 elderly patients. Almost two-thirds of clinical specimens were harvested from the respiratory tract. The most frequently reported pathogens from 3094 Gram-negative bacterial isolates were Klebsiella spp., Acinetobacter spp., and Escherichia coli. During the studied period, almost 40% of all the Klebsiella spp. strains were multidrug-resistant (MDR)/extensively drug-resistant (XDR), with a significant increase in the resistance to cephalosporins (p ≤ 0.05), fluoroquinolones (p ≤ 0.05), and carbapenems (imipenem—(p ≤ 0.05), ertapenem—p < 0.001). The proportion of carbapenem-non susceptible Klebsiella spp. rose from 24.41% in 2023 to 32.48% in 2024, p = 0.01. Two-thirds of Acinetobacter spp. isolates were MDR/XDR, and over 80% were carbapenem-non-susceptible in 2023–2024. The results draw attention to the need to quickly adopt measures to reduce the prevalence, limit the transmission of MDR/XDR pathogens, and improve therapeutic protocols in this age category. Full article

Objectives: This study aimed to compare clinical characteristics, antimicrobial susceptibility, and 28-day mortality between patients with Acinetobacter baumannii bacteremia (ABB) and non-baumannii Acinetobacter bacteremia (NBAB) after rapid matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) species identification. Methods: We retrospectively reviewed the clinical data of adult ABB and NBAB patients over >7 years. Multivariate logistic regression was used to identify the risk factors for 28-day mortality. Results: Of 273 episodes of Acinetobacter species bacteremia, 224 (82.1%) were ABB and 49 (17.9%) were NBAB. NBA isolates were predominantly A. nosocomialis (49%), with smaller proportions of A. bereziniae, A. junii, A. ursingii, and others. The primary sites of infection in NBAB cases were the intra-abdomen, urinary tract, intravascular catheters, and lungs. While only 4.0% of A. baumannii isolates were susceptible to carbapenem, 87.8% of non-baumannii Acinetobacter isolates were susceptible. Multivariate analysis revealed that low carbapenem resistance was independently associated with NBAB. Additionally, a higher Pitt bacteremia score, septic shock, continuous renal replacement therapy, inappropriate empirical antibiotic therapy, and thrombocytopenia were independent risk factors for the 28-day mortality in patients with ABB. Conclusions: Although less common than ABB, NBAB cases are increasing and exhibit lower carbapenem resistance. Rapid MALDI-TOF MS identification enables timely and appropriate antibiotic treatment. The key factors driving the 28-day mortality include illness severity, septic shock, renal replacement therapy, inappropriate antibiotics, and thrombocytopenia, highlighting the need for early risk assessments and tailored management. Ongoing surveillance and species-specific strategies are essential for combating resistant Acinetobacter infections. Full article

Background/Objectives: Non-fermenting Gram-negative bacilli (NFGNB) represent a significant clinical challenge due to their intrinsic and acquired resistance, particularly in immunocompromised patients. Infections cause by NFGNB are associated with high morbidity and mortality, especially among patients with cystic fibrosis and hematologic malignancies. This study aimed to assess the in vitro susceptibility of clinically relevant NFGNB isolates to two newer antibiotics, cefiderocol and aztreonam/avibactam, and an established antibiotic, trimethoprim/sulfamethoxazole. Methods: This retrospective, monocentric study analysed 94 NFGNB isolates (30 Pseudomonas aeruginosa, 30 Acinetobacter sp., 24 Stenotrophomonas maltophilia, and 10 Burkholderia cepacia complex). Susceptibility testing for cefiderocol, aztreonam/avibactam, and trimethoprim/sulfamethoxazole was conducted using gradient strip method. MIC values were interpreted using EUCAST breakpoints, ECOFFs, or alternative criteria when necessary. Results: All S. maltophilia isolates were susceptible to cefiderocol (FCR) and aztreonam/avibactam (A/A) based on ECOFFs, with one strain resistant to trimethoprim–sulfamethoxazole (COT). Burkholderia cepacia complex strains also showed high susceptibility to FCR, with only one isolate exceeding the ECOFF for A/A, and 20% resistant to COT. All Acinetobacter sp. isolates were susceptible to FCR; however, most MIC values clustered at or just below the ECOFF value. In P. aeruginosa, one isolate was resistant to FCR, and three isolates (10%) were resistant to A/A. Interestingly, confirmed carbapenemase producers remained susceptible to both FCR and A/A. Most A/A MIC values for P. aeruginosa were just below the ECOFF. Conclusions: Cefiderocol and aztreonam/avibactam demonstrated promising in vitro activity against clinically relevant NFGNB, including carbapenem-resistant strains. These findings support their potential role as therapeutic options for difficult-to-treat infections, particularly in immunocompromised patients. Full article

Background: Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The reference standard is the broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB). Still, it is cumbersome for routine clinical laboratory use, while variable accuracy has been reported with available commercial systems. Variability in interpretive criteria and areas of technical uncertainty (ATUs) further complicate assessments. Methods: This review and expert opinion presents: (1) an overview of non-susceptibility to FDC and then delves into the performance of current FDC AST methods for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex; (2) a practical decision framework to guide clinical microbiologists in making informed choices. Results and Conclusions: For Enterobacterales, including carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa, we propose disk diffusion (DD) as a preliminary screening tool to classify isolates as susceptible (S) or resistant (R). Confirmatory testing using the UMIC^® FDC system or the ID-CAMHB BMD method is recommended for R isolates. In cases of discrepancy, repeating the test with ID-CAMHB BMD is advised. Additionally, isolates falling within the ATU during DD testing should be retested using the UMIC^® system or ID-CAMHB BMD. For A. baumannii complex, since EUCAST breakpoints have not been defined yet, we propose a stepwise framework based on the first DD result: isolates with inhibition zones < 17 mm are considered non-susceptible and should be confirmed with standard BMD. Those between 17 and 22 mm require retesting with a commercial BMD method, with further confirmation recommended if S isolates with zones ≥ 23 mm may be considered S without additional testing. Full article

Gram-negative ESKAPE pathogens pose major challenges to global public health due to their multidrug resistance and virulence. The present study aimed to study the prevalence and resistance of Gram-negative ESKAPE pathogens at a tertiary care hospital in Eastern India. A retrospective analysis was conducted on 7343 non-duplicate isolates collected between January 2023 and December 2024. The bacterial isolates and their antibiotic susceptibility testing were identified using Kirby–Bauer disk diffusion techniques and the VITEK 2 Compact system, adhering to CLSI 2025 and EUCAST 2024 guidelines. Our findings indicate that Klebsiella pneumoniae was the most common isolate, followed by Pseudomonas aeruginosa, Acinetobacter baumannii complex, and Enterobacter cloacae complex, predominantly affecting male patients aged 18–64 years. Importantly, most of these isolates exhibit increased multidrug resistance (MDR) to several key antibiotics, including β-lactams and carbapenems, which further complicates the treatment process. The analysis of seasonal dynamics revealed an increased abundance of infections in monsoon and post-monsoon periods. These findings will be useful in understanding AMR in hospital environments and in developing strategies to prevent the occurrence and spread of antimicrobial resistance among pathogens. Full article

Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article

Background: The global rise of multidrug-resistant Gram-negative bacteria, particularly non-fermenting species and carbapenemase-producing Enterobacteriaceae, poses a significant challenge to hospital infection control. Methods: In this study, a total of 89 Acinetobacter spp. isolates, 14 Pseudomonas aeruginosa, and 14 carbapenem-resistant Enterobacteriaceae isolates were collected from patients in a tertiary hospital. Whole-genome sequencing and antimicrobial susceptibility testing were conducted. Resistance mechanisms and evolutionary relationships were analyzed using phylogenetic analysis and genetic context mapping. Results: Among the non-fermenting isolates, A. baumannii exhibited high resistance to carbapenems, clustering into distinct clonal groups enriched with genes associated with biofilm formation and virulence genes. P. aeruginosa isolates harbored fewer resistance genes but carried notable mutations in the efflux pump systems and the oprD gene. In Enterobacteriaceae, four bla_NDM alleles were identified within a conservative structural sequence, while bla_KPC-2 was located in a non-Tn4401 structure flanked by IS481- and IS1182-like insertion sequences. Phylogenetic analysis revealed that bla_NDM-positive E. coli strains were closely related to susceptible lineages, indicating horizontal gene transfer. Conversely, K. pneumoniae isolates harboring bla_KPC-2 formed a tight clonal cluster, suggesting clonal expansion. Conclusions: The study reveals distinct transmission patterns between resistance genes: horizontal dissemination of bla_NDM and clonal expansion of bla_KPC-2 in K. pneumoniae. These findings emphasize the need for resistance-gene-specific genomic surveillance and infection control strategies to prevent further nosocomial dissemination. Full article

Background/Objectives: As antimicrobial resistance patterns of Gram-negative bacteria change over time, this study aimed to analyze the antimicrobial susceptibility trends of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates in Tunisia. Methods: From 1999 to 2019, non-duplicate isolates of Gram-negative bacteria were collected from 11 Tunisian hospitals as part of an antimicrobial resistance surveillance program. Antimicrobial susceptibility testing was performed using the disk diffusion method according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Results: Out of 213,434 isolates collected during the study period, 58.8% were E. coli, 22% were K. pneumoniae, 14.4% were A. baumannii, and 4.8% were P. aeruginosa, with 67% of the isolates sourced from urine samples. E. coli showed a significant increase in resistance to third-generation cephalosporins (3GC), from 5.4% in 2004 to 16.5% in 2019, but K. pneumoniae displayed a rising trend of resistance to imipenem, from 1% in 2005 to 18.6% in 2019; meanwhile, amikacin remained effective against K. pneumoniae isolates. P. aeruginosa did not exhibit a significant change in resistance to imipenem. A. baumannii had a high resistance rate to imipenem that increased from 34.5% in 2008 to 84.2% in 2019 and had low susceptibility rates to all other antibiotics tested. Conclusions: This study reveals high carbapenem resistance among K. pneumoniae and A. baumannii in Tunisia. A. baumannii shows alarming multidrug resistance that requires urgent control measures. Full article

Background: Bloodstream infections (BSIs) caused by multidrug-resistant non-fermenting Gram-negative bacilli, particularly Pseudomonas aeruginosa and Acinetobacter baumannii, represent a growing public health concern, especially in tertiary care settings. This study aimed to describe the epidemiological and antimicrobial resistance trends of P. aeruginosa and A. baumannii isolated from blood cultures over an eight-year period (2017–2024) at a tertiary infectious disease hospital in Bucharest, Romania, especially in the context of the disruption caused by the SARS-CoV-2 pandemic. Methods: A retrospective study was conducted on 43,951 blood cultures processed at the National Institute of Infectious Diseases. Species identification and antibiotic susceptibility testing (AST) were performed using VITEK2, MALDI-TOF MS, and supplementary phenotypic methods. AST interpretation followed EUCAST guidelines. Results: Out of all of the positive blood cultures, 112 (3.63%) were P. aeruginosa and 158 (5.12%) A. baumannii. Multidrug-resistance (MDR) was identified in 46% of P. aeruginosa and 90.73% of A. baumannii isolates. Resistance trends varied, with P. aeruginosa showing a decrease in MDR rates post-COVID-19 pandemic and following antimicrobial stewardship implementation. In contrast, A. baumannii displayed persistently high resistance, with carbapenem and aminoglycoside resistance rates reaching 100% by 2024. Colistin resistance, though low overall, increased in the latter years. Conclusions: The findings highlight the dynamic nature of antimicrobial resistance among P. aeruginosa and A. baumannii. Effective infection control and antimicrobial stewardship programs are crucial in curbing the rise of MDR strains, particularly amid healthcare system disruptions such as the COVID-19 pandemic. Full article

Background/Objectives: Empirical antimicrobial therapy for neonatal early-onset sepsis (EOS) comprises ampicillin and gentamicin. However, multidrug-resistant organisms are increasing worldwide, thus inflicting a global burden. We identified the incidence and risk factors of neonates with pathogenic isolates that were not susceptible to treatment comprising a combination of ampicillin and gentamicin (non-susceptible group). Methods: This retrospective study included neonates diagnosed with EOS between 2004 and 2023. All patients with EOS and positive culture results within 72 h of birth were reviewed. Patients in the non-susceptible and susceptible groups were analyzed using a multivariable logistic regression model. Results: Sixty pathogenic isolates and 55 neonates with EOS were observed over the course of 20 years. The incidence and case fatality rates of EOS were 0.88 per 1000 live births and 41.8%, respectively. Acinetobacter baumannii was the most common EOS pathogenic isolate (19/60 pathogenic isolates; 12/19 resistant to carbapenems). Pathogenic isolates were susceptible to ampicillin or gentamicin (59%), ampicillin or cefotaxime (42%), and ampicillin or amikacin (72%). Data regarding susceptibility to ampicillin and gentamicin of 49 neonates were available. A multivariable analysis revealed that patients in the non-susceptible group (n = 18) were more likely to experience late-onset EOS (48–72 h; p = 0.01) and require endotracheal intubation on day 1 (p = 0.04) compared to patients in the susceptible group (n = 31). Conclusions: In areas with high multidrug resistance, broader-spectrum antibiotic therapy (ampicillin plus amikacin) should be considered for neonates who develop clinical sepsis within 48–72 h of birth and experience respiratory failure at birth. Full article