Search Results (392)

Diabetic wounds infected with multidrug-resistant bacteria represent a major clinical challenge due to delayed healing and limited therapeutic options. In this study, we evaluated the therapeutic efficacy and biosafety of a biopolymeric skin patch loaded with the predatory bacterium Bdellovibrio bacteriovorus HD100 in a murine model of diabetic wounds infected with Pseudomonas aeruginosa. In vitro assays demonstrated that B. bacteriovorus HD100 reduced P. aeruginosa populations by approximately 3 log units within 48 h. In vivo, diabetic mice treated with the B. bacteriovorus-loaded patch achieved complete wound closure within $12\pm 1$ days, compared with $16\pm 1$ days in mice treated with conventional antibiotic therapy (piperacillin/tazobactam, 16 mg/kg; single dose). Non-diabetic mice treated with biopolymeric patches, with or without the predatory bacterium, exhibited complete wound closure within 9–10 days. Molecular analysis by PCR revealed no detectable dissemination of B. bacteriovorus DNA to internal organs (liver, spleen, kidney, or brain), indicating the systemic biosafety of topical application. Overall, these results demonstrate that B. bacteriovorus-based skin patches significantly accelerate wound closure in infected diabetic wounds and represent a promising localized biological alternative to conventional antibiotic therapy. Full article

Background/Objectives: Antimicrobial resistance (AMR) in companion animals is an emerging public health threat due to zoonotic potential and limited therapeutic options. Dogs with otitis externa may harbor multidrug-resistant (MDR) bacteria, including Escherichia coli (E. coli), Proteus mirabilis (P. mirabilis), and Enterobacter cloacae complex (E. cloacae complex), some producing extended-spectrum beta-lactamase (ESBL) or AmpC β-lactamases. This study aimed to assess the prevalence, AMR patterns, MDR occurrence, β-lactamase production, and co-infection profiles of these pathogens in canine otitis externa. Methods: Ear canal samples were collected from 592 dogs presenting clinical signs of otitis externa, with one sample per dog included in the analysis. Samples were collected from veterinary clinics in Timiș County, Romania, from 2022 to 2025. Samples were cultured on blood agar and MacConkey agar, followed by biochemical testing and MALDI-TOF mass spectrometry for bacterial identification. Antimicrobial susceptibility testing against 15 agents across six classes was performed using the VITEK^® 2 system. MDR and β-lactamase production (ESBL, AmpC) were determined according to CLSI 2018 veterinary guidelines. Co-isolation with bacterial and fungal species were recorded. Results: E. coli, P. mirabilis, and E. cloacae complex were isolated in 9.12%, 6.25%, and 1.2% of cases, respectively. E. coli exhibited the highest resistance to aminoglycosides (tobramycin 72.2%, gentamicin 61.1%) and full susceptibility to carbapenems. P. mirabilis showed the highest resistance to ampicillin (54%) and trimethoprim + sulfamethoxazole (46%), with complete susceptibility to carbapenems and fluoroquinolones. E. cloacae complex displayed universal resistance to cephalosporins but remained susceptible to non-cephalosporin β-lactams (piperacillin–tazobactam), carbapenems and aminoglycosides. MDR prevalence was 35.2% for E. coli, 18.9% for P. mirabilis, and 14.3% for the E. cloacae complex. ESBL production was detected in 13% of E. coli and 8.1% of P. mirabilis isolates, while all E. cloacae complex isolates were AmpC-positive. Co-isolations were common, primarily involving Staphylococcus pseudintermedius (S. pseudintermedius) and Malassezia pachydermatis (M. pachydermatis). Conclusions: MDR and β-lactamase-producing bacteria were identified in dogs with otitis externa, emphasizing the importance of routine antimicrobial susceptibility testing, targeted therapy based on local resistance profiles, and continuous AMR surveillance to prevent treatment failure and mitigate zoonotic risk. Full article

Clostridium tertium is an emerging opportunistic pathogen typically associated with immunocompromised hosts, yet it can also cause serious infections in non-neutropenic individuals. We present a case of postoperative peritonitis and bacteremia caused by C. tertium in a non-neutropenic 75-year-old woman following emergency obturator hernia repair. Diagnosis was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and successful treatment was achieved with piperacillin–tazobactam combined with levornidazole alongside surgical source control. A review of 128 cumulative cases (including ours) revealed two distinct patterns: bacteremia in severely neutropenic patients versus a broader spectrum of localized and bloodstream infections in non-neutropenic hosts, often linked to intestinal barrier disruption. Mortality was largely driven by underlying comorbidities and polymicrobial sepsis. These findings indicate that C. tertium infection should be considered in non-neutropenic patients with postoperative or gastrointestinal barrier-disruptive infections, especially when there is a poor response to initial empiric therapy. Consequently, in such clinical scenarios, empirical therapy should be guided by its unique resistance pattern, favoring carbapenems, vancomycin, or piperacillin–tazobactam, often combined with a nitroimidazole, alongside urgent source control. Full article

Background/Objectives: Butyricimonas species constitute a genus of Gram-negative, anaerobic bacteria that are part of the human gut microbiota. Infections caused by these organisms are extremely rare in clinical practice. While uncommon in the general population, their occurrence is higher among immunocompromised individuals or patients with significant underlying health conditions. This review aims to compile and analyze all reported cases of human Butyricimonas infections, focusing on epidemiology, microbiological characteristics, antimicrobial resistance patterns, treatment strategies, and associated mortality. Methods: This review was conducted using data retrieved from the PubMed/MEDLINE and Scopus databases. Results: A total of 14 publications described Butyricimonas infections affecting 14 patients. The mean age of those affected was 66.46 years, and 10 (71.4%) were male. The most frequently reported predisposing factor was a history of malignancy, observed in almost one-third of cases (30.8%). Clinically, fever, organ dysfunction, and shock were the most common presentations (fivecases), followed by sepsis and the need for ICU in fourpatients. In vitro studies indicated that the isolates were generally susceptible to carbapenems and metronidazole, with only high resistance levels observed to penicillin. Among the antimicrobial therapies used, carbapenems were the most commonly administered (50%), followed by piperacillin/tazobactam (41.7%) and metronidazole (33.3%). The overall mortality rate across the cohort was 16.7%, with infection-attributable deaths representing 8.3% of cases. Conclusions: Given the potential of Butyricimonas species to cause severe infections, clinicians should consider this organism in patients presenting with unexplained bacteremia or intra-abdominal infections, particularly in the setting of mucosal disruption or immune dysfunction. Full article

Objective: To investigate how the high-altitude environment modifies severe pertussis in young infants and analyze its pathophysiological mechanisms and clinical management implications. Methods: Clinical data of two young infants with severe pertussis residing at 3650 m were retrospectively analyzed, including presentation, laboratory findings, pathogen detection, treatment, and outcomes. A literature review explored synergistic interactions between high-altitude factors and pertussis pathophysiology. Results: Case 1 had macrolide-resistant Bordetella pertussis (MRBP, 23S rRNA A2047G) with peak WBC 52.25 × 10⁹/L, and received cefoperazone-sulbactam, piperacillin-tazobactam and azithromycin, and was successfully treated with trimethoprim-sulfamethoxazole combined with exchange transfusion. Case 2 had Bordetella pertussis confirmed by PCR with peak WBC 36.55 × 10⁹/L, receiving cefoperazone-sulbactam and azithromycin, and recovered. Both developed respiratory failure requiring non-invasive ventilation and survived without pulmonary hypertension. High-altitude stressors—hypoxia, enhanced pulmonary vascular reactivity, and hypercoagulability—synergize with pertussis-induced hyperleukocytosis as a “dual hit,” accelerating cardiopulmonary deterioration and elevating thrombotic risks. Conclusions: High altitude is an independent risk modifier in infantile pertussis, demanding heightened vigilance and proactive interventions: early non-invasive ventilation, prophylactic anticoagulation, and timely exchange transfusion before pulmonary hypertension develops. This is the first high-altitude case series that provides essential insights for clinicians in similar environments globally, guiding early recognition and proactive management strategies to improve outcomes in this vulnerable population. Full article

Background: The goal of this study was to characterize the microbial etiology, antimicrobial susceptibility, and temporal resistance trends of early-onset neonatal sepsis (EOS) pathogens in a tertiary neonatal intensive care unit over 10 years (2014–2023), assessing empirical therapy adequacy and mortality associations. Methods: Retrospective analysis was performed on the positive blood cultures of neonates with confirmed EOS, born between 1 January 2014 and 31 December 2023. Blood was aseptically collected into PEDS Plus/BC bottles, incubated using the BACTEC system, with pathogen identification by biochemical assays or MALDI-TOF MS. Susceptibility testing followed EUCAST disk-diffusion standards, with additional resistance assays. Results: Among 6631 NICU admissions, 39 neonates met EOS criteria (31 preterm, 8 term). In preterm infants, Gram-negative Enterobacterales—mainly E. coli (n = 20)—predominated, while GBS was most common in term infants. All GBS isolates (n = 7) were susceptible to benzylpenicillin and vancomycin. Although 90% of E. coli were ampicillin-resistant, 90–95% remained susceptible to third-generation cephalosporins, piperacillin–tazobactam, and aminoglycosides. Two E. coli isolates produced ESBL but remained susceptible to aminoglycosides and carbapenems. Mortality was higher in E. coli EOS (50%) than in GBS (0%) or other pathogens (25%), with borderline significance (p = 0.0547; adjusted RR 1.55, 95% CI 0.54–4.41). Ampicillin resistance was not associated with increased mortality. No annual resistance trends were observed. Conclusions: In this 10-year NICU cohort, the etiology of EOS differed markedly between preterm and term neonates. Recommended empirical ampicillin–aminoglycoside therapy demonstrated in vitro efficacy against most neonatal bloodstream isolates pending pathogen identification. However, the widespread ampicillin resistance, particularly among E. coli strains, supports consideration of cephalosporin–aminoglycoside combinations or meropenem monotherapy when rapid beta-lactam bactericidal activity is clinically essential. Mortality was higher in E. coli EOS, though not statistically significant, and unrelated to ampicillin resistance. Full article

Background and Objectives: Sepsis and septic shock remain leading causes of morbidity and mortality in intensive care settings worldwide. While substantial epidemiological data exist from Western countries, the clinical profile of sepsis in regions with exceptionally high diabetes prevalence remains inadequately characterized. Saudi Arabia, with one of the highest diabetes mellitus prevalence rates globally, may exhibit distinct sepsis epidemiology, infection patterns, and outcomes. This study aimed to characterize the clinical profiles, antimicrobial management, and outcomes of sepsis and septic shock in a tertiary intensive care unit (ICU) in the Aseer region of southwestern Saudi Arabia. Materials and Methods: A retrospective observational study was conducted including 263 adults meeting Sepsis-3 criteria (232 sepsis, 31 septic shock) admitted to a tertiary ICU between January 2020 and December 2024. Demographics, comorbidities, laboratory parameters, microbiological data, antibiotic timing, interventions, and in-hospital mortality were analyzed. Logistic regression identified independent mortality predictors. This study adhered to the STROBE reporting guidelines. Results: The median age was 73 years with male predominance (58.4%). Diabetes mellitus (71.5%) and hypertension (65.8%) were highly prevalent. Urinary tract infections (UTIs) predominated (79.8%), with Escherichia coli as the most common pathogen (26.2%). The median time to antibiotic administration was 1.8 h; piperacillin–tazobactam was the most frequent empiric regimen (43.7%). Septic shock patients exhibited higher creatinine (1.65 vs. 1.08 mg/dL, p = 0.026) and lower platelets (194 vs. 271 × 10³/μL, p = 0.030). Mortality was 38.7% in septic shock versus 8.2% in sepsis (p < 0.001). Multivariate analysis confirmed septic shock (aOR: 5.23; 95% CI: 1.89–14.48) and mechanical ventilation (aOR: 15.42; 95% CI: 5.67–41.95) as independent mortality predictors. Conclusions: High diabetes prevalence shapes regional sepsis epidemiology with UTI predominance. Early antibiotic administration and recognition of septic shock remain critical for improving outcomes in this population. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global public health threat, particularly in hospitals. Antimicrobial Stewardship Programs (ASPs) aim to optimize prescribing, reduce unnecessary exposure to broad-spectrum agents, and mitigate resistance. This study evaluated the clinical, ecological, and economic impact of an ASP implemented in January 2021 in a high-complexity hospital in Brazil, focusing on antimicrobial consumption, temporal trends in bacterial susceptibility, and direct antimicrobial-related costs. Methods: A quasi-experimental pre–post study using an interrupted time-series design was conducted in the adult intensive care unit from January 2019 to December 2023. Antimicrobial consumption was measured as Defined Daily Doses per 1000 patient-days (DDD/1000-PD) for ceftriaxone, meropenem, piperacillin–tazobactam, vancomycin, and polymyxin B. Temporal trends were assessed using Joinpoint regression, and pre- and post-intervention periods were compared using Student’s or Mann–Whitney tests. Susceptibility data were interpreted according to BrCAST standards. Results: Significant and sustained reductions were observed for all agents except polymyxin B. Susceptibility improved or stabilized among key Gram-negative pathogens, with a significant increase in aggregated Gram-negative susceptibility after 2021, while intrinsically resistant organisms showed limited change. Annual antimicrobial costs decreased by approximately USD 174,000. Conclusions: The ASP was associated with reduced broad-spectrum antimicrobial use, favorable ecological trends, and substantial cost savings. Full article

Background/Objectives: The rising prevalence of extended-spectrum beta-lactamase (ESBL)-producing pathogens has emerged as a significant challenge in the treatment of pyelonephritis. This study aims to determine the frequency of ESBL-producing agents in hospitalized patients with pyelonephritis, identify associated risk factors, and assess the appropriateness of empirical antimicrobial therapy. Methods: This prospective study included patients hospitalized with pyelonephritis in the Infectious Diseases Clinic of Ankara Training and Research Hospital between 1 October 2022 and 29 February 2024. Demographic features, comorbidities, urinary system pathologies, history of urinary tract interventions, hospitalization more than one month prior, antibiotic use within the previous three months, and prior urinary tract infections were compared between patients infected with ESBL-producing and non-ESBL-producing organisms. Antimicrobial susceptibility profiles and the appropriateness of empirical treatments were evaluated. Statistical analyses were performed using SPSS version 25.0, with p < 0.05 considered statistically significant. Results: Escherichia coli (n = 142) and Klebsiella spp. (n = 43) were isolated in 180 of 204 patients. ESBL positivity was detected in 95 patients (52.7%). In the multivariate logistic regression analysis, male sex (p = 0.038) and hospitalization more than one month prior (p = 0.016) were identified as independent risk factors for ESBL positivity, while prior antibiotic use in the last three months showed a borderline association (p = 0.055) and did not reach statistical significance. ESBL production was not associated with prolonged hospitalization; however, bacteremia significantly increased length of stay (p < 0.001). Antimicrobial susceptibility rates were markedly lower in the ESBL-positive group. The appropriateness of empirical therapy was also significantly reduced, with piperacillin–tazobactam being the most frequently inappropriate agent due to high resistance rates and unnecessary broad-spectrum use. Conclusions: ESBL-producing pathogens were highly prevalent among hospitalized patients with pyelonephritis. The low appropriateness of empirical therapy in ESBL-positive cases underscores the need for careful evaluation of ESBL risk factors prior to treatment initiation, as ESBL rates may approach 50%. Full article

Background: Chagas disease is a major public health problem, especially in Latin American countries, and benznidazole and nifurtimox are currently the only drugs available for its treatment. However, they present several disadvantages, such as low availability, high toxicity, and limited efficacy, which often result in treatment discontinuation. In recent decades, bioinformatics studies have accelerated the field of drug repurposing, reducing time and costs. In this study, the aim was to identify novel cruzain inhibitors from the analogs of FDA-approved drugs with trypanocidal activity. Methods: A ligand-based virtual screen, along with molecular docking analysis, was carried out, and the selected compounds were evaluated for their trypanocidal activity against trypomastigotes of two endemic Mexican strains and their inhibitory activity on cysteine proteases. Results: A cefsulodin analog (LC₅₀ = 126.18 and 77.50 µM), two flucloxacillin analogs (LC₅₀ = 94.05 and 101.73 µM; 48.74 and 64.49 µM), and one piperacillin analog (LC₅₀ = 48.46 and 83.68 µM) had better trypanocidal activity and selectivity index against the NINOA and INC-5 strains than the reference drugs. Enzymatic evaluation showed that all four compounds inhibited cysteine proteases (IC₅₀ < 840.03 µM). Furthermore, molecular dynamics simulations predicted the stability of the compound–protein complex, while the docking test on human cathepsin L predicted their potential selectivity. Finally, our in silico analysis of ADMET properties showed that all compounds exhibited favorable profiles. Conclusions: These results encourage the development of new and more potent anti-Trypanosoma cruzi agents using FDA-approved drugs as scaffolds. Full article

Background. Antibiotic resistance is a growing global health challenge, complicating the management of infections. Aminoglycosides are increasingly associated with resistance, raising the risk of clinical complications and mortality in severe infections. This study aimed to characterize the epidemiological profile of 135 aminoglycoside-resistant clinical strains collected in Setif between 2021 and 2023. Methods. Antibiotic susceptibility testing was performed according to EUCAST guidelines, and phenotypic assays were conducted to assess key virulence traits, including biofilm formation and enzyme production. Results. Aminoglycoside resistance was more frequently observed in female patients (55.6%) and was found to be predominant among adults (68.1%). Urinary tract infections represented the main clinical presentation (76.3%), with Escherichia coli being the most common isolate (40.7%). High resistance rates were detected for amoxicillin (83%), amoxicillin–clavulanic acid (80%), cephalexin (74.8%), cefixime (71.1%), trimethoprim–sulfamethoxazole (74.8%), and gentamicin (72.6%). Conversely, chloramphenicol (53.3%), imipenem (47.4%), amikacin (47.4%), and piperacillin–tazobactam (31.1%) remained comparatively more effective. Multidrug resistance involving seven antibiotics occurred in 25.6% of isolates, with notable cross-resistance patterns between gentamicin and β-lactam antibiotics (5 out of 22). Genotypic analysis showed that 43% of isolates carried at least one β-lactamase gene, whereas 9.6% harbored a qnr determinant. Regarding virulence factors, isolates with low biofilm-forming ability were found to be the most common (62.96%). Conclusion. In conclusion, this study revealed substantial variations in aminoglycoside resistance in Setif, shaped by demographic, clinical, and bacteriological factors. Full article

Antimicrobial resistance (AMR) is accelerating and driven by antimicrobial use. Hospital consumption and resistance data remain scarce in Serbia. This retrospective study assessed the prevalence of infectious agents among hospitalized patients (2019–2022), distribution and AMR rates of Escherichia coli and Klebsiella pneumoniae, antimicrobial consumption, and associations between AMR and antibiotic use (Spearman’s correlation). All bacterial isolates were included for species-frequency analyses. For AMR and specimen distribution, repeat isolates of E. coli and K. pneumoniae per patient were excluded. Among 10,780 isolates, E. coli remained most frequent (24.7% in 2019; 24.3% in 2022), whereas K. pneumoniae increased from 7.7% to 16.9% (p < 0.001). E. coli resistance to cephalosporins, fluoroquinolones, and piperacillin/tazobactam increased significantly from 2019 to 2022 (p < 0.05). K. pneumoniae resistance increased to most agents (p < 0.001), with meropenem resistance rising from 11.7% to 52.0%. Multidrug resistance rose from 27.3% to 35.4% for E. coli (2020–2022; p = 0.006) and from 62.4% to 82.9% for K. pneumoniae (2019–2022; p < 0.001). Total hospital antibiotic consumption nearly doubled from 57 to 111.8 Defined Daily Doses per 100 bed days (2019–2021) and decreased to 52.0 (2022). Temporal concurrence of increased antimicrobial use during COVID-19 and escalating resistance underscores the need for strengthened surveillance and stewardship. Full article

Background: Empirical antibacterial therapy for febrile neutropenia requires adaptation to local epidemiology, a process that is often complex, time-consuming, and prone to human error. This study aims to address this challenge by developing a practical, data-driven tool to efficiently evaluate and adapt treatment protocols. Methods: We developed a novel, open-source computational script in Python (version 3.10), aided by large language models for code revision, to analyze antibiotic susceptibility data. The script was validated using a retrospective dataset of 237 Gram-negative bloodstream infections (BSIs) from 2015 to 2024 in cancer or hematopoietic stem cell transplant recipients at a tertiary care pediatric hospital in Italy. The script calculates efficacy metrics for both single agents and two-drug combinations. Results: Among the Gram-negative BSI strains analyzed, meropenem monotherapy demonstrated the highest efficacy (median 95.4%). In contrast, piperacillin/tazobactam and cefepime showed lower efficacy (80.3% and 81.8%, respectively). On the contrary, combination therapy, particularly with amikacin, significantly increased the efficacy of beta-lactams, elevating their effectiveness to a level comparable to meropenem. Conclusions: The developed script is a valuable tool for antimicrobial stewardship programs, offering a rapid and accessible method to validate international guidelines against local epidemiological data. While meropenem shows high efficacy, its broad use should be limited to prevent resistance. The combination of piperacillin–tazobactam and amikacin is identified as a robust and effective empirical treatment choice. Full article

Background/objectives: A rise in infections associated with carbapenem-resistant Providencia species (CRPS) has been observed worldwide. This study presents a genomic analysis of CRPS isolates from four hospitals in Croatia and the outpatient setting, in order to determine the extent of the spread of CRPS in Croatia. In the present study, we applied a combination of phenotypic characterization and molecular analysis of resistance traits to determine the mechanisms and the routes of spread of CRPS. Material and methods: The antibiotic susceptibility testing was performed using disk-diffusion and broth dilution methods. The nature of extended-spectrum β-lactamases (ESBLs), carbapenemases, and fluoroquinolone resistance determinants was investigated by polymerase chain reaction (PCR). In order to obtain an insight into the whole resistome, selected isolates were subjected to the Interarray Genotyping Kit CarbaResist and whole genome sequencing (WGS). Results: In total, 30 isolates were collected from four centers, located in different geographic regions of Croatia. There was uniform resistance to piperacillin-tazobactam, cefuroxime, expanded-spectrum cephalosporins (ESCs), imipenem, ertapenem, meropenem, and ciprofloxacin. Immunochromatographic testing and PCR revealed OXA-48 and NDM carbapenemase in 15 isolates, respectively. Phenotypic tests for ESBLs were positive in all OXA-48 and one NDM-positive organism (16 isolates). The isolates were categorized as extensively drug-resistant (XDR). OXA-48-producing isolates were susceptible only to ceftazidime-avibactam, whereas NDM producers were susceptible to cefiderocol and, in the majority of cases, also to amikacin. WGS identified a plethora of genes encoding resistance to aminoglycosides, such as aadA1 and aadA2, (aph(3″)-Ib and aph(6)-Id, sulfonamides sul1 and sul2, trimethoprim dfrA1, dfrA10, and dfrA12, tetracyclines tet(A) and tet(B), and chloramphenicol catA3 and catA5. Conclusions: Providencia spp., in spite of being a rare pathogen, should be included in the surveillance studies across the medical centers in Croatia. Full article

Introduction: Infections attributed to multidrug-resistant organisms have resulted in a significant clinical burden, high mortality, and excessive costs. Identifying the most appropriate and efficacious treatments will aid in reducing these burdens. Imipenem/cilastatin + relebactam (I/R) is used against multidrug-resistant infections providing an alternative option which may support patients where traditional treatments are no longer effective. Objective: The objective was to evaluate the efficacy of I/R for complicated urinary tract infections, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia, based on data aggregated from randomized controlled trials. Method: Two systematic literature reviews were conducted to include randomized controlled trials which aligned with the inclusion criteria reporting on the efficacy of I/R against placebo or other comparators such as piperacillin/tazobactam or colistin. The outcomes of interest were mortality, clinical response, and microbiological response. Results: The results found reduced mortality and comparable clinical and microbiological response with I/R versus its comparators. I/R displayed the largest favorable clinical and microbiological responses within high-risk populations, including those with severe renal impairment when compared with piperacillin/tazobactam. Conclusions: These findings support the efficacy of I/R for key Gram-negative infections, particularly within vulnerable patient populations. Despite the favorable outcomes reported, there is a need for further real-world evidence generation to support the efficacy of I/R to aid in standardizing treatment guidelines and reducing the clinical and economic burden associated with multidrug-resistant bacterial infections. Full article