Search Results (452)

Background/Objective: This study aimed to evaluate the effectiveness of very early oral transition in Enterobacterales bloodstream infections (E-BSIs), identify factors associated with it, compare the effectiveness of different oral options, and assess its economic and ecological benefits. Methods: Retrospective, observational cohort study including monomicrobial E-BSI in clinically stable adult patients by day 3 of bacteremia with oral antibiotic options. Transition to oral antibiotics by day 3 or earlier (early oral (EO) group) was compared to later transition or remaining on intravenous therapy (nEO group). Early oral transition-associated factors were analyzed. Oral high-dose beta-lactams (BLs) were compared to quinolones (QLs) or trimethoprim/sulfamethoxazole (TS). Economic and ecological costs were assessed. Results: Of 345 E-BSI, 163 (47.2%) were in the EO group, characterized by more urinary tract infections (UTIs) and shorter hospital stays. The nEO group had higher Charlson Comorbidity Index (CCI), extended-spectrum beta-lactamase (ESBL) production, greater source control need, and longer time to clinical stability. There were no significant differences in mortality and relapse. UTIs were associated with early oral transition (OR 2.02, IC 95% 1.18–3.48), while higher CCI (0.85, 0.77–0.95), source control need (0.39, 0.19–0.85), longer time to clinical stability (0.51, 0.39–0.66), and ESBL isolates (0.39, 0.19–0.80) hindered this practice. High-dose BLs and QL/TS were equally effective. Early oral transition resulted in 38.794 KgCO₂eq reduction and EUR 269,557.99 savings. Conclusions: Very early oral transition at day 3 or before in stable E-BSI patients is effective, eco-sustainable, and cost-effective; UTI is related with the early oral switch, while comorbidities, ESBL production, source control need, or longer time to clinical stability hinder this practice. Full article

Background/Objectives: Caesarean section (CS) accounts for over 20% of global births and routinely involves perioperative antibiotic prophylaxis (PAP) to reduce surgical site infections. While the impact of such prophylaxis on neonatal microbiome development is well described, effects on the maternal gut microbiome remain underexplored. This systematic review synthesizes current evidence on how antibiotic prophylaxis during CS affects maternal gut microbiome composition and diversity—an underrepresented, but clinically relevant aspect of maternal–fetal medicine. Methods: A systematic literature search was conducted in Medline (PubMed), the Cochrane Library, and the WHO International Clinical Trials Registry Platform (ICTRP) through November 2024. Inclusion criteria were defined according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies used molecular techniques to report maternal gut microbiome outcomes (alpha- and beta-diversity). The search concentrated on beta-lactam antibiotics. Reference lists were screened, but no additional grey literature was searched. Synthesis followed the Synthesis Without meta-analysis (SWiM) approach. No review protocol was registered. The review received no external funding. Results: Out of 1011 records, three studies (total 286 mothers) met the inclusion criteria. All reported maternal microbiome outcomes secondarily to infant-focused research. Only one study provided pre- and post-birth stool samples. Applied antibiotic regimens, sequencing methods, and reported microbiome metrics for alpha- and beta-diversity varied considerably, thus limiting comparability of results. Due to high heterogeneity, no formal risk of bias was assessed. While taxonomic diversity changes were inconsistent, significant shifts in functional diversity metrics were observed postpartum. Conclusions: Evidence on maternal microbiome disruption following perioperative antibiotic prophylaxis in CS is methodologically fragmented and limited by small sample sizes and inconsistent antibiotic protocols. Nonetheless, functional diversity appears sensitive to antibiotic exposure. To improve clinical understanding and safety, maternal-focused studies using standardized protocols are urgently needed. The maternal microbiome may play a key role in both recovery and shaping the newborn’s early microbial environment. Full article

Introduction: In recent years, antimicrobial resistance (AMR) rates have increased significantly in bacterial pathogens, particularly extended beta-lactam resistance. This study aimed to investigate resistome and phylogenomics of Escherichia coli (E. coli) strains isolated from various sources in Jimma, Ethiopia. Methods: Phenotypic antibiotic resistance patterns of E. coli isolates were determined using automated Kirby–Bauer disc diffusion and minimum inhibitory concentration (MIC). Isolates exhibiting phenotypic resistance to beta-lactam antibiotics were further analyzed with a DNA microarray to confirm the presence of resistance-encoding genes. Additionally, multilocus sequence typing (MLST) of seven housekeeping genes was conducted using PCR and Oxford Nanopore-Technology (ONT) to assess the phylogenetic relationships among the E. coli isolates. Results: A total of 611 E. coli isolates from human, animal, and environmental sources were analyzed. Of these, 41.6% (254) showed phenotypic resistance to at least one of the tested beta-lactams, 96.1% (244) thereof were confirmed genotypically. More than half of the isolates (53.3%) had two or more resistance genes present. The most frequent ESBL-encoding gene was CTX-M-15 (74.2%; 181), followed by TEM (59.4%; 145) and CTX-M-9 (4.1%; 10). The predominant carbapenemase gene was NDM-1, detected in 80% (12 out of 15) of carbapenem-resistant isolates. A phylogenetic analysis revealed clonality among the strains obtained from various sources, with international high-risk clones such as ST131, ST648, ST38, ST73, and ST405 identified across various niches. Conclusions: The high prevalence of CTX-M-15 and NDM-1 in multidrug-resistant E. coli isolates indicates the growing threat of AMR in Ethiopia. The discovery of these high-risk clones in various niches shows possible routes of transmission and highlights the necessity of a One Health approach to intervention and surveillance. Strengthening antimicrobial stewardship, infection prevention, and control measures are crucial to mitigate the spread of these resistant strains. Full article

Antimicrobial use in food animals selects for antimicrobial-resistant (AMR) bacteria, which most commonly reach humans via the food chain. However, AMR bacteria can also escape the feedyard via agricultural runoff, manure used as crop fertilizer, and even dust. A study published in 2015 reported AMR genes in dust from cattle feedyards; however, one of the study’s major limitations was the failure to investigate gene presence in viable bacteria, or more importantly, viable bacteria of importance to human health. Our main objective was to investigate the presence and quantity of viable bacteria and antimicrobial-resistant (AMR) determinants in fugitive bioaerosols from cattle feedyards in the downwind environment. Six bioaerosol sampling campaigns were conducted at three commercial beef cattle feedyards to assess variability in viable bacteria and AMR determinants associated with geographic location, meteorological conditions, and season. Dust samples were collected using four different sampling methods, and spiral plated in triplicate on both non-selective and antibiotic-selective media. Colonies of total aerobic bacteria, Enterococcus spp., Salmonella enterica, and Escherichia coli were enumerated. Viable bacteria, including AMR bacteria, were identified in dust from cattle feedyards. Bacteria and antimicrobial resistance genes (ARGs via qPCR) were mainly found in downwind samples. Total suspended particles (TSPs) and impinger samples yielded the highest bacterial counts. Genes encoding beta-lactam resistance (bla_CMY-2 and bla_CTX-M) were detected while the most common ARG was tet(M). The predominant Salmonella serovar identified was Lubbock. Further research is needed to assess how far viable AMR bacteria can travel in the ambient environment downwind from cattle feedyards, to model potential public health risks. Full article

The global rise of carbapenem-resistant Acinetobacter baumannii (CRAB) strains poses a critical challenge to healthcare systems due to limited therapeutic options and high mortality rates, especially in intensive care settings. This review explores the epidemiological landscape and molecular mechanisms driving carbapenem resistance, including the production of diverse beta-lactamases (particularly OXA-type enzymes), porin loss, efflux pump overexpression, and mutations in antibiotic targets. Emerging treatment strategies are discussed, such as the use of new beta-lactam–beta-lactamase inhibitor combinations (e.g., sulbactam–durlobactam), siderophore cephalosporins, next-generation polymyxins, as well as novel agents like zosurabalpin and rifabutin (BV100). Alternative approaches—including phage therapy, antimicrobial peptides, CRISPR-based gene editing, and nanoparticle-based delivery systems—are also evaluated for their potential to bypass traditional resistance mechanisms. Furthermore, advances in artificial intelligence and multi-omics integration are highlighted as tools for identifying novel drug targets and predicting resistance profiles. Together, these innovations represent a multifaceted strategy to overcome CRAB infections, yet their successful implementation requires further clinical validation and coordinated surveillance efforts. This analysis highlights the urgent need for continued investment in innovative treatments and effective resistance monitoring to limit the spread of CRAB and protect the effectiveness of last-line antibiotics. Full article

Neonatal sepsis is a major cause of morbidity and mortality in neonates. A particular concern is the increasing prevalence of antibiotic-resistant strains among neonatal intensive care units (NICUs). Two novel beta-lactam/beta-lactamase inhibitors have recently been approved for use in neonates with multidrug-resistant infections: ceftazidime/avibactam and ceftolozane/tazobactam. These agents demonstrate efficacy against a range of multidrug-resistant gram-negative pathogens, including extended-spectrum beta-lactamases (ESBL)-producing and carbapenem-resistant Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa. This narrative review aims to summarize the current knowledge concerning the utilization of ceftazidime/avibactam and ceftolozane/tazobactam in the NICU. According to the existing literature, both agents have been shown to be highly effective with a favorable safety profile in the neonatal population. Full article

Background: Urinary tract infections represent a significant healthcare burden, particularly among vulnerable patients with chronic comorbidities. In this case report, we describe a UTI caused by Kluyvera ascorbata exhibiting an AmpC resistance pattern in an 85-year-old male with stage IV chronic kidney disease and a history of ESBL-positive infection. Methods: A comprehensive diagnostic workup was performed, including clinical evaluation, laboratory tests (urinalysis, complete blood count, renal function tests), and microbiological cultures with antibiogram analysis using the MicroScan WalkAway (Beckman Coulter, Brea, United States) and VITEK2 Compact systems (bioMérieux, Marcy L’Étoile or Craponne, France). Results: The initial urine culture revealed a Gram-negative bacillus and subsequent identification confirmed K. ascorbata, which demonstrated resistance to ampicillin and cefazolin while remaining susceptible to meropenem. The patient received intravenous meropenem therapy for 10 days, resulting in clinical improvement and a subsequent negative urine culture. Conclusions: This case reports a complicated urinary tract infection caused by K. ascorbata with an AmpC resistance pattern, highlighting the importance of considering this infrequently reported pathogen and its resistance profile in vulnerable patients. Its multidrug-resistant profile underscores the necessity for vigilant antimicrobial stewardship and further research to develop standardized treatment protocols for managing infections caused by this organism. Full article

Background/Objectives: Antibiotic management of hospitalized penicillin-allergic patients (PAPs) is associated with prolonged hospital stays, adverse reactions and treatment failure, resulting in increased healthcare costs. This study aimed to estimate the cost-effectiveness of beta-lactam desensitization (DES) in the management of PAPs. Methods: A cost-effectiveness analysis was performed using a probabilistic model with 1000 s-order Monte Carlo simulations. Hospital costs (in 2025 Euros) and effectiveness outcomes (cure and survival rates) were derived from a Spanish retrospective case–control study conducted between 2015 and 2022, which included 56 PAPs (14 in the desensitization group [DES] and 42 in the control group without DES [NDES]; ratio 1:3), and collected healthcare costs per patient. Results: The incremental cost of the DES group was EUR 37,805 (95% CI: EUR 2023–EUR 126,785), with a 100% probability of incurring additional costs compared to the NDES group. The cure rate was 16.5% higher in the DES group (95% CI: 13.3–20.0%), and the estimated gain in life-years per patient (LYG) was 1.42 (95% CI: 1.15–1.73) versus NDES. The cost per life-year gained (LYG) with DES versus NDES was EUR 24,618 ± EUR 19,535 (95% CI: EUR 1755–EUR 73,488). The probability that DES would be cost-effective (cost per LYG < EUR 25,000 and <EUR 30,000) was 61.1% and 100%, respectively. Conclusions: According to this analysis, DES appears to be a cost-effective option for managing PAPs. These findings should be confirmed in clinical studies with larger sample sizes. Full article

Background: Due to the high prevalence of severe infections, antibiotics are frequently administered in anaesthesia and intensive care units. Despite their therapeutic efficacy, several antibiotics exhibit neurotoxic potential, resulting in central and peripheral neurological complications in patients. This review aims to summarise the current evidence on antibiotic-induced neurotoxicity, particularly in critical care settings. Methods: A comprehensive literature analysis was performed to assess the neurotoxic profiles, underlying mechanisms, and clinical manifestations associated with different antibiotic classes, including beta-lactams, fluoroquinolones, macrolides, aminoglycosides, and others. Results: Beta-lactam antibiotics (especially cephalosporins and carbapenems) are strongly associated with seizures, encephalopathy, and EEG abnormalities, mainly through GABAergic inhibition and mitochondrial dysfunction. Fluoroquinolones and macrolides can cause psychosis, insomnia, and neuropathy via NMDA activation and oxidative stress. Linezolid carries the risk of serotonin syndrome and optic neuropathy, while glycopeptides and aminoglycosides are primarily associated with ototoxicity. Risk factors include advanced age, renal or hepatic impairment, and high serum drug levels. Conclusions: The neurotoxic potential of antibiotics is a critical but under-recognised aspect of pharmacotherapy in intensive care. Improved awareness, pharmacovigilance, dose adjustment, and drug monitoring are crucial for mitigating adverse neurological effects. Full article

Background/Objectives: The increasing occurrence of carbapenem resistance A. baumannii (CRAB) has forced clinicians to seek out alternative options with activity against CRAB. CRAB with inactivated PBP7/8 has been shown to result in an increased outer membrane permeability and could serve as a potential new adjuvant target. Methods: Two isogenic clinical isolates of A. baumannii HUMC1 were utilized (WT and HUMC1 ΔPBP7/8). Static concentration time-kill assays were performed against both isolates with escalating exposures to antibiotics. The resulting data were modeled using the Monolix software suite to capture parameters related to bacterial killing and PBP7/8 synergism. The model results were used to prospectively simulate clinically relevant antibiotic dosing of three antibiotics under physiological conditions and were validated using a hollow-fiber infection model (HFIM). Results: Treatment with monotherapy or combination therapy resulted in concentration-dependent killing for both isolates. Bacterial killing was greater with HUMC1 ΔPBP7/8 for all tested antibiotic concentrations. The mean bacterial population reduction was 4.38 log₁₀ CFU/mL for HUMC1 and 5.38 log₁₀ CFU/mL for HUMC1ΔPBP7/8 knockout isolate. The final mechanism-based model demonstrated improved antibacterial activity with PBP7/8 inhibition through a decline in KC₅₀ values of 59.7% across the beta-lactams in the PBP7/8 knockout. HFIM observations that were retrospectively compared to the simulated model-predicted bacterial concentration time course showed our final model was able to appropriately capture changes in bacterial population within a dynamic HFIM scenario. Conclusions: The quantification of KC₅₀ decline and increase in effectiveness of previously sidelined antimicrobial therapies with PBP7/8 inhibition suggests PBP7/8 is a promising potential target for an antibacterial adjuvant. This lends further support to advance to next-stage studies for identifying compounds that specifically inhibit PBP7/8 activity. Full article

Background/Introduction: Beta-lactam antibiotics are among the most frequently prescribed drugs in clinical practice, yet their therapeutic drug monitoring remains underutilized despite high interindividual pharmacokinetic variability, especially in critically ill patients. Methods: To address this, we developed and validated an ultra-high-performance liquid chromatography (UHPLC-UV/Vis) method for the simultaneous quantification of six beta-lactams (cefepime, ceftolozane, ceftazidime, meropenem, ampicillin, and ertapenem) in plasma. Results: This method uses a single gradient mobile phase and a photodiode array detector, ensuring accurate separation, minimal interference, and robust analyte identification. Validation followed EMA bioanalytical guidelines, demonstrating selectivity, precision, accuracy, and linearity within clinically relevant ranges (1.0–50.0 mg/L). Stability tests showed that the analytes were stable in plasma for up to seven days at 4 °C and one month at −20 °C. Pilot clinical implementation in 35 patients revealed significant interindividual variability, supporting the need for routine beta-lactam monitoring. Approximately 26% of trough concentrations were below the minimal inhibitory concentration, while others exceeded thresholds associated with potential toxicity. Discussion: This study represents the first UHPLC-UV/Vis method for the simultaneous determination of these six beta-lactams, overcoming limitations of prior methods that required different mobile phases or excluded clinically relevant antibiotics. The method is universally applicable and easily transferable to routine clinical practice. Conclusions: These findings underline the importance of beta-lactam monitoring in optimizing treatment outcomes and combating antibiotic resistance in vulnerable populations. Further studies to assess free drug concentrations are warranted to enhance clinical applicability. Full article

Background: Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing E. coli is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been introduced in recent years. While these agents have shown efficacy, their clinical utility is constrained by high cost, limited availability, and emerging resistance mechanisms. The rational of this study was to test the in vitro activity of a cost-effective alternative to currently available BL–BLI combinations against ESBL-producing E. coli isolated from urinary tract infections (UTIs). Objective: This study investigates the in vitro antimicrobial activity of cefaclor (CFC), both as monotherapy and in combination with the β-lactamase inhibitors clavulanic acid (CA) and sulbactam (SUL), against 52 ESBL-producing E. coli isolates derived from urine cultures of patients diagnosed with UTIs. Methods: The susceptibility ranges were measured by disk diffusion and minimal inhibitory concentration (MIC) methods. In addition, the Time kill assay and disk approximation method were performed to measure the synergistic and bactericidal activity of the approached combination. Results: The MIC50 and MIC90 for CFC were improved from more than 128 µg/mL to 8/4 µg/mL when CFC was combined with either CA or SUL. The triple combination format of CFC/CA/SUL showed MIC50 and MIC90 values at 8/4/4 µg/mL and 64/32/32 µg/mL, respectively. The recovered susceptibility percentages were 54%, 54%, and 58% for CFC/CA, CFC/SUL, and CFC/CA/SUL combinations, respectively. Disk approximation and time–kill assay results revealed synergy and bactericidal effects when CFC combined with CA or SUL for isolates that showed susceptibility restorations of CFC when coupled with CA or SUL by the disk diffusion and MIC method. Conclusions: This study proposes a cost-effective combination that could mitigate resistance development and offer a sparing option to last resort treatment choices including carbapenems. However, testing efficacy in a clinical setting is crucial. Full article

Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide which usually presents as mild, and self-limiting disease in immunocompetent individuals. However, in immunocompromised patients, such as those with common variable immunodeficiency, C. jejuni can cause severe recurrent infections requiring antibiotic treatment. Our study reports a case of a 37-year-old male patient with CVID, who had multiple episodes of C. jejuni intestinal infections over a 3.5-year period. A total of 27 stool samples were collected and analyzed between December 2020 and July 2024 during acute febrile diarrheal episodes, with C. jejuni isolated in 15 samples. Antimicrobial susceptibility testing (AST) during the course of the disease revealed three different antimicrobial resistance profiles including multi-drug-resistant phenotype. Whole genome sequencing was performed on three representative isolates, all identified as MLST type 367, ST-257 complex, with minimal genetic divergence, indicating a clonal origin. Genes and point mutations conferring resistance to macrolides, fluoroquinolones, beta-lactams, and tetracycline were identified in different C. jejuni isolates, along with key virulence factors linked to adherence, invasion, motility, and immune evasion. The genetic analysis of macrolide phenotypic resistance revealed different resistance mechanisms. Genotypic and phenotypic analyses of the same C. jejuni clone from single patient, and identified multidrug resistance pattern, present the first documented case of in vivo resistance development of C. jejuni in Croatia. This case highlights the role of prolonged antibiotic pressure in driving resistance evolution and underscores the need for careful antimicrobial stewardship and genomic monitoring in immunocompromised patients. Further research is needed to correlate phenotypic resistance with genetic determinants in Campylobacter spp. Full article

The blue crab (Callinectes sapidus) is an invasive alien species in the Mediterranean Sea, posing threats to biodiversity, fisheries, and aquaculture. Climate change has worsened these challenges, influencing the distribution of bacterial species, including Shewanella species, which are sensitive to changes in temperature and salinity. In this study, 300 blue crabs were sampled between June and October 2024 from the Sacca di Goro (Northern Adriatic Sea, Italy) to investigate the prevalence of Shewanella species in their haemolymph. The prevalence was found to be 7% (21/300), with species such as S. mesophila, S. algae, S. cowelliana, and S. baltica identified, particularly in the months of September and October. Molecular techniques, including MALDI-TOF MS and rpoB gene amplification, were used to identify isolates. Antibiotic susceptibility testing (AST) revealed a trend of resistance to beta-lactam antibiotics. A network analysis was also conducted to examine the global trends of Shewanella research in relation to humans, animals, and the marine environment. While proper cooking eliminates the risk to consumers, handling without personal protective equipment can increase exposure, particularly for vulnerable individuals such as those who are elderly or immunocompromised. Mild symptoms are observed in children. Further studies, particularly with a One Health approach, are crucial to better understand the transmission dynamics and evolving antibiotic resistance of Shewanella species. Full article

Acute diarrhoeal disease caused by antibiotic-resistant diarrhoeagenic bacteria is a significant global public health issue, particularly in low- and middle-income countries. This study provides the first molecular characterisation of antimicrobial resistance profiles, including the detection of CTX-M-15 and CTX-M-55 extended-spectrum beta-lactamases (ESBLs), among diarrhoeagenic Enterobacterales in Bioko Island, Equatorial Guinea, offering novel epidemiological insights into an understudied region. This study investigated the antibiotic resistance profiles of pathogenic bacteria isolated from diarrhoeal samples on Bioko Island. A total of 153 clinical isolates were collected between 1 February and 30 May 2014, and antimicrobial susceptibility testing was performed at Loeri Comba Polyclinic (Malabo) using the Kirby–Bauer method. The molecular characterisation of β-lactamase-associated genes was performed on different isolates of diarrhoeagenic pathotypes—144 Escherichia coli, 7 Salmonella enterica, and 2 Shigella flexneri—at the National Centre for Microbiology (Majadahonda, Spain). High resistance rates were detected against ampicillin (98%), tetracycline (93.5%), sulfonamides (94.8%), sulfamethoxazole–trimethoprim (88.2%), and cefotaxime (78.8%), while moderate rates of resistance were noted for ciprofloxacin (26.7%), and all isolates remained susceptible to imipenem. Of the isolates, 107 (69.9%) produced either single or multiple β-lactamases. Among these, 73 (68.2%) harbored classical β-lactamases, specifically TEM and OXA-1 types, representing 47.7% of the total sample. Additionally, 34 (31.8%) of the isolates were identified as producers of extended-spectrum β-lactamases (ESBLs), specifically CTX-M enzymes. Sequencing identified CTX-M-15 and CTX-M-55 variants. The predominant ESBL-producing bacteria were enteroaggregative Escherichia coli (56.2%), followed by enteropathogenic and enterotoxigenic E. coli. These findings confirm the circulation of multidrug-resistant diarrhoeagenic Enterobacterales in Equatorial Guinea, raising concerns about limited treatment options due to widespread resistance to multiple antibiotic classes, including third-generation cephalosporins and quinolones. The most important conclusion drawn from this study is that a high percentage of diarrhoeagenic bacteria have an antibiotic resistance and multi-resistance profile, especially to beta-lactams and other groups of antibiotics such as tetracyclines and sulphonamides. There is also a moderate prevalence of isolates carrying ESBLs on Bioko Island, Equatorial Guinea, which could indicate the inappropriate use of antimicrobials. Full article