Search Results (599)

Micro-organisms are abundant in nature and can also be found in hospital settings, causing high rates of infections. This study aimed to identify bacteria isolated from a veterinary hospital, as well as to perform antimicrobial susceptibility testing using the disk diffusion method (Kirby–Bauer), biofilm production tests using 96-well polystyrene microtiter plates and crystal violet dye, and genetic analysis of the ica operon of Staphylococcus isolates. Three collections were made from eleven surfaces and objects in the hospital’s non-critical areas (general areas) and critical areas (surgical center), totaling thirty-three samples. A total of 66 different bacterial isolates were obtained, with 77% (51/66) Gram-positive and 23% (29/66) Gram-negative. Resistance profiles were found for multidrug-resistance (MDR), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and other unidentified species of methicillin-resistant coagulase-negative (MRCNS) and extended-spectrum beta-lactamase (ESBL), as well as biofilm production rates of 57% (38/66) of the isolates. Analysis of the operon genes for Staphylococcus sp. showed divergence in some samples when compared to the phenotypic test performed. In summary, there is a high presence of micro-organisms with resistance and virulence factors spread throughout the various areas of the veterinary hospital. Full article

Cefepime-enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination showing good activity against multidrug-resistant (MDR) Gram-negative bacteria producing a variety of β-lactamases. In this systematic review, we aimed to evaluate the available data on resistance to this drug. We performed a thorough search of four databases (Embase, PubMed, Scopus, and Web of Science), as well as backward citation searching, to identify studies containing data on resistance to cefepime-enmetazobactam. The data were extracted and analyzed according to the breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA), or the specific breakpoints reported by the authors of the respective studies. Analysis based on the type of lactamases produced by the isolates was also performed. Ten studies reported in vitro susceptibility testing and mechanisms of antimicrobial resistance. The total number of isolates was 15,408. The activity of cefepime-enmetazobactam against β-lactamase-producing isolates was variable. The resistance of the studied extended-spectrum β-lactamase (ESBL)-producing and ampicillin C β-lactamase (AmpC)-producing isolates was low (0–2.8% and 0%, respectively). The resistance was higher among oxacillinase-48 β-lactamase (OXA-48)-producing and Klebsiella pneumoniae carbapenemase (KPC)-producing isolates (3.4–13.2% and 36.7–57.8%, respectively). High resistance was noted among metallo-β-^lactamase (MBL)-producing isolates (reaching 87.5% in one study), especially those producing New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM), which had the highest rates of resistance. The high activity of cefepime-enmetazobactam against Enterobacterales and selected lactose non-fermenting Gram-negative pathogens, including ESBL-producing and AmpC-producing isolates, makes it a potential carbapenem-sparing agent. The drug should be used after in vitro antimicrobial susceptibility testing in patients with infections caused by OXA-48, KPC, and MBL-producing isolates. Full article

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Feline urinary tract infections (UTIs) present a common challenge in veterinary practice, underscoring the importance of understanding local bacterial pathogens and antimicrobial resistance (AMR). This study determined bacterial prevalence and antimicrobial susceptibility in cats at Kasetsart University’s Veterinary Teaching Hospital in Bangkok, Thailand. Of the 543 cystocentesis urine samples collected from 428 cats, 115 (21.2%) tested positive for bacterial cultures, leading to a diagnosis of UTIs in 95 cats (22.2%). The most prevalent isolates included Escherichia coli (24.8%), Staphylococcus species (19.2%), Proteus mirabilis (13.6%), Pseudomonas aeruginosa (12.0%), and Enterococcus species (12.0%). Staphylococcus felis (8.8%) and Staphylococcus pseudintermedius (5.6%) were the predominant Staphylococcus species. Rare pathogens such as Corynebacterium urealyticum and Lactococcus garvieae were also identified. Antimicrobial testing revealed alarming resistance, with 69.2% of isolates exhibiting multidrug resistance (MDR). Escherichia coli and Proteus mirabilis showed high resistance to amoxicillin/clavulanic acid (AMC) (45.2–70.6%) and sulfamethoxazole/trimethoprim (SXT) (51.6–52.9%). Enterococcus faecium exhibited 85.7% resistance to AMC. Methicillin resistance was identified in 41.7% of Staphylococcus isolates, particularly high in Staphylococcus epidermidis (75.0%) and Staphylococcus pseudintermedius (71.4%). High fluoroquinolone resistance among MDR isolates further exacerbates AMR concerns. These results indicate that MDR Gram-negative, Staphylococcus, and Enterococcus species complicate the empirical treatment of feline UTIs, highlighting significant implications for AMR in veterinary practice. Full article

Background and Objectives: Cancer patients are particularly susceptible to infections caused by multidrug-resistant Gram-negative bacteria (MDR GNB) due to chemotherapy- or radiation therapy-induced immunosuppression. Colistin is often prescribed as a last-resort agent for MDR GNB infection, but its clinical benefit in oncology patients remains unclear. This study aims to evaluate the mortality risk associated with colistin versus non-colistin regimens in cancer patient with MDR GNB infections, stratified by resistance profiles, infection sites, and concomitant medication use. Materials and Methods: A retrospective cohort study was conducted in adult cancer patients with MDR GNB infections that are resistant to at least three antibiotic classes and identified from at least two anatomical sites at a tertiary care hospital in Korea. Propensity score-matched in a 1:3 ratio either to the colistin group or non-colistin group and multivariate Cox hazard regression analyses were used to evaluate mortality in cancer patients with MDR GNB infections, primarily Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Results: A total of 85 patients (29 patients in the colistin and 56 patients in the non-colistin group) were included in the analysis. Overall, colistin use did not show a statistically significant mortality benefit compared to non-colistin regimens (hazard ratio (HR) 0.93, 95% CI 0.47–1.87). However, the subgroup analysis revealed that colistin had a potential association with significantly lower mortality in pneumonia patients with aminoglycoside-resistant infections (HR 0.04, 95% CI 0.002–0.69). Concomitant use of antipsychotics and benzodiazepines in selected resistance profiles also correlated with improved outcomes. In contrast, a potential association was found between concomitant macrolide use and increased mortality in patients with fluoroquinolone- or penicillin-resistant profiles. Conclusions: Colistin may offer survival benefits in selected high-risk cancer patients with MDR GNB pneumonia. Treatment outcomes are influenced by resistance profiles, infection sites, and concomitant medications, indicating the significant importance of individualized antimicrobial therapy and antimicrobial stewardship in oncology patients. Full article

Infections with multidrug-resistant (MDR) organisms remain a significant cause of morbidity and mortality among liver transplant recipients, despite advances in surgical techniques and immunosuppressive therapy. This prospective observational study aimed to evaluate the impact of targeted perioperative antibiotic prophylaxis against MDR Gram-negative bacteria on postoperative infections and mortality in liver transplant recipients. Seventy-nine adult patients who underwent liver transplantation and were admitted to the ICU for more than 24 h postoperatively were included. Demographics, disease severity scores, comorbidities, and lengths of ICU and hospital stay were recorded. Colonization with carbapenem-resistant Gram-negative bacteria was assessed via preoperative and postoperative cultures from the blood, urine, rectum, and tracheal secretions. Patients were divided into two groups: those with MDR colonization or infection who received targeted prophylaxis and controls who received standard prophylaxis. Infectious complications (30.4%) occurred significantly less frequently than non-infectious ones (62.0%, p = 0.005). The most common infections were bacteremia (22.7%), pneumonia (17.7%), and surgical site infections (2.5%), with most events occurring within 15 days post-transplant. MDR pathogens isolated included Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Although overall complication and mortality rates at 30 days and 3 months did not differ significantly between groups, the targeted prophylaxis group had fewer infectious complications (22.8% vs. 68.5%, p = 0.008), particularly bacteremia (p = 0.007). Infection-related mortality was also significantly reduced in this group (p = 0.039). These findings suggest that identification of MDR colonization and administration of targeted perioperative antibiotics may reduce septic complications in liver transplant patients. Further prospective studies are warranted to confirm benefits on outcomes and resource utilization. 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

Objectives: Cefideroccol (FDC) is a siderophore cephalosporin with potent antibacterial activity against a wide range of Gram-negative multidrug-resistant (MDR) microorganisms. We investigated the anti-biofilm capacity of FDC against clinical strains. Methods: This multicenter study was conducted on 28 selected strains of MDR Gram-negative bacilli isolated from clinical samples of Pseudomonas aeruginosa (n = 5), Acinetobacter baumannii (n = 11), and Klebsiella pneumoniae (n = 12). We first determined the minimum inhibitory concentration (MIC) of each strain using the microdilution method. We also defined the minimum biofilm inhibitory concentration (MBIC) as a ≥50% reduction in tetrazolium salt (XTT) (as recommended in the 2017 Spanish Microbiology Protocols [SEIMC] for the microbiological diagnosis of infections related to the formation of biofilms). We also analyzed the reduction in the following biofilm variables after an 8 mg/mL FDC treatment: the CFU count, the cell viability, the biomass, the metabolic activity, and extracellular α or β polysaccharides. Results: The MIC₅₀ and MBIC₅₀ of FDC were 0.5 mg/L and 64 mg/L, respectively. We observed a mean (SD) fold increase in the susceptibility to FDC between planktonic and sessile cells for P. aeruginosa, A. baumannii, and K. pneumoniae of 9.60 (0.55), 6.27 (2.28), and 6.25 (2.80), respectively. When 8 mg/mL of FDC was tested, we observed that the best median (IQR) percentage reductions were obtained for cell viability and the extracellular matrix (73.1 [12.4–86.5] and 79.5 [37.3–95.5], respectively), particularly for P. aeruginosa. The lowest percentage reduction rates were those obtained for biomass. Conclusions: We demonstrated that the susceptibility to FDC was significantly reduced when strains were in a biofilm state. The best percentage reduction rates for all biofilm-defining variables were observed for P. aeruginosa. Our results need to be validated using a larger collection of clinical samples. Full article

Background: Klebsiella variicola is a Gram-negative, capsulated, nonmotile, facultative anaerobic rod. It is one of the species belonging to the K. pneumoniae complex. The objective of this study was to gain insights into the antimicrobial resistance and virulence of K. variicola strains isolated from clinical samples from oncologic patients. Methods: Strain identification was performed using a mass spectrometry method. Whole genome sequencing was conducted for all analyzed strains. Antimicrobial susceptibility was determined using an automated method. The presence of antimicrobial resistance mechanisms and genes encoding extended-spectrum beta-lactamases (ESBL) was assessed using the double-disc synergy test and genotypic methods. Results: All isolates were identified as K. variicola using mass spectrometry and whole genome sequencing (WGS). All isolates were ESBL-positive, and two of them harbored the bla_CTX-M-15 gene. In our study, the bla_LEN-17 gene was detected in all strains. Genome sequence analysis of the K. variicola isolates revealed the presence of virulence factor genes, including entAB, fepC, ompA, ykgK, and yagWXYZ. Two different plasmids, IncFIB(K) and IncFII, were identified in all of the analyzed K. variicola strains. The detected virulence factors suggest the ability of the bacteria to survive in the environment and infect host cells. All isolates demonstrated in vitro susceptibility to carbapenems. Conclusions: Further studies are needed to confirm whether multidrug-resistant K. variicola strains represent an important pathogen in infections among oncologic patients. Full article

Background: Combining direct disk diffusion (DD) testing with antimicrobial stewardship (AMS) may optimize antibiotic use and improve outcomes in patients with Gram-negative bloodstream infections (GNBSIs). Methods: This quasi-experimental study was conducted at Srinagarind Hospital, Khon Kaen University, between 13 September 2022 and 11 April 2023. Patients with GNBSIs were enrolled during two phases: a standard care phase (13 September 2022–2 January 2023) and an intervention phase (16 January 2023–11 April 2023), during which therapy adjustments were guided by DD results interpreted by infectious disease specialists. Results: Among the 141 patients included (68 in the standard care group and 73 in the intervention group), the mean age was 61.7 years, and 60.2% were male. Escherichia coli (36.5%) and Klebsiella pneumoniae (27.6%) were the most frequently isolated pathogens, with intra-abdominal and urinary tract infections being the most common sources. Multidrug-resistant (MDR) organisms were identified in 48.9% of cases. Compared to standard care, the intervention group had a significantly shorter median time to optimal therapy (40.0 vs. 59.1 h, p = 0.037) and a higher proportion of patients receiving optimal therapy within 72 h (86.2% vs. 62.3%, p = 0.002). While 30-day mortality did not differ significantly between groups (17.2% vs. 16.7%, p = 0.98), MDR bacteremia and ICU admission were associated with increased mortality. In contrast, receiving optimal therapy within 72 h was associated with reduced mortality. Conclusion: Direct DD testing combined with AMS significantly reduced the time to optimal antibiotic therapy and decreased inappropriate antibiotic use in GNBSI patients. Achieving optimal therapy within 72 h was associated with a trend toward reduced mortality. 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

Burn wound infections remain a major clinical challenge due to delayed healing, scarring, and the risk of sepsis, especially when complicated by multidrug-resistant (MDR) Gram-negative pathogens and biofilm formation. Acellular dermal matrices (ADMs) are widely used in reconstructive and burn surgery, yet they lack intrinsic antimicrobial activity, necessitating their combination with topical agents. Background/Objectives: This study investigates the antimicrobial and cytocompatibility profiles of ADMs impregnated with various antimicrobial agents, using in vitro planktonic and biofilm burn wound models. While the incorporation of antimicrobials into scaffolds has been previously explored, this study is, to our knowledge, the first to directly compare seven clinically relevant antimicrobial agents after they were impregnated into an ADM in a standardized in vitro model. Methods: Seven topical antimicrobials were tested against MDR Pseudomonas aeruginosa and Acinetobacter baumannii from burn patients. Results: The ADM with 1% acetic acid (AA) showed superior antimicrobial activity, achieving > 7 log₁₀ reductions in planktonic assays and complete inhibition of P. aeruginosa biofilms. In NIH 3T3 fibroblast cytotoxicity assays, the 1% AA ADM maintained cell viability at control levels, indicating excellent biocompatibility. Compared with agents such as Betadine^®, Octenilin^®, and colistin, which showed cytotoxicity, and Prontosan^®, which showed low efficacy, 1% AA uniquely combined potent antibacterial effects with minimal toxicity. Conclusions: Among the seven antimicrobial agents impregnated into ADMs, 1% AA demonstrated a unique efficacy and safety profile, supporting its potential for clinical application in integrated wound dressings and implantable biomaterials for infection control in burn care. Full article

Colistin has re-emerged as a last-resort antibiotic for treating infections caused by multidrug-resistant (MDR) Gram-negative bacilli (GNB). However, increasing resistance threatens its efficacy. This study aimed to evaluate colistin resistance trends among clinical isolates of Gram-negative bacilli isolated over a five-year period at a large Emergency Hospital in North-Eastern Romania. A total of 23,143 GNB strains were isolated during the study period, including 14,531 Enterobacterales and 8294 non-fermenting Gram-negative bacilli. The percentage of colistin-resistant strains among those analyzed was 3.98%. Species-specific analysis focused on Klebsiella spp., Escherichia coli, Enterobacter spp., Citrobacter spp., Pseudomonas spp., and Acinetobacter spp. Klebsiella spp. exhibited the highest prevalence of colistin resistance, accounting for over 80% of all colistin-resistant strains, with annual resistance rates fluctuating between 12.97% and 21.64%. Colistin resistance among E. coli was low (0.18–1.25%). Citrobacter spp. showed no resistance in the last three years of the study, and Enterobacter spp. maintained relatively stable resistance (3–5%). Resistance in Pseudomonas spp. remained below 1%, while Acinetobacter spp. showed a resistance rate of 5.43%. Several distinct resistance phenotypes were identified among Klebsiella spp., Pseudomonas spp., and Acinetobacter spp. strains, reflecting both endemic and sporadic circulation patterns. The study highlights a persistent presence of colistin resistance, especially in Klebsiella spp., underlining the importance of ongoing surveillance. Despite low resistance in other species, the emergence of resistant strains underscores the need for robust antimicrobial stewardship and infection control policies. Full article

Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem–relebactam (I/R), a novel β-lactam/β-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective–prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (≥18 years) treated with I/R for ≥48 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22/29 patients (75.9%), while 30-day mortality was 24.1% (7/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem–relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies. Full article

The increasing circulation of multi-drug-resistant pathogens, coupled with the sluggish development of new antibiotics, is weakening our capacity to combat human infections, resulting in elevated death tolls. To address this worldwide crisis, antimicrobial peptides (AMPs) are viewed as promising substitutes or adjuvants for combating bacterial infections caused by multidrug-resistant organisms. Here, the antimicrobial activity and structural characterization of a novel 13-amino acid cationic peptide named RKW (RKWILKWLRTWKK-NH2), designed based on known AMPs sequences and the identification of a key tryptophan-rich structural motif, were described. RKW displayed a broad-spectrum and potent antimicrobial and antibiofilm activity against Gram-positive and Gram-negative pathogens, including ESKAPE bacteria and fungi with minimal inhibitory concentrations (MBC) ranging from 5 µM to 20 μM. Structural results by fluorescence and Circular Dichroism (CD) spectroscopy revealed that the peptide was folded into a regular α-helical conformation in a membrane-like environment, remaining stable in a wide range of pH and temperature for at least 48 h of incubation. Furthermore, RKW showed low toxicity in vitro against mammalian fibroblast cells, indicating its potential as a promising candidate for the development of new antimicrobial or antiseptic strategies. Full article