Antibiotics-Basel最新文献

Objective: In the present study, we used phenotypic and molecular methods to determine susceptibility to oxacillin in coagulase-negative staphylococci (CoNS) and estimate the prevalence of strains with low-level resistance to oxacillin, mecA-positive oxacillin-susceptible methicillin-resistant (OS-MRCoNS), and borderline oxacillin-resistant (BORCoNS). Methods: One hundred one CoNS strains were screened for oxacillin and cefoxitin susceptibility using phenotypic (disk diffusion, agar dilution, latex agglutination, and chromagar) and molecular (detection of mecA, mecB, and mecC) methods. Staphylococcal cassette chromosome mec (SCCmec) typing was performed. Results: Sixteen (15.8%) CoNS strains were mecA-positive, and 85 (84.2%) were mec-negative. Seven (6.9%) were classified as OS-MRCoNS, accounting for 43.8% of all mecA-positive strains. Twelve (11.9%) mec-negative strains were classified as borderline oxacillin resistant (BORCoNS). Compared with MRCoNS and BORCoNS, OS-MRCoNS strains demonstrated lower resistance to non-beta-lactams. SCCmec type I cassette was predominant. The disc-diffusion method with oxacillin accurately predicted OS-MRCoNS strains but did not provide reliable results for BORCoNS strains. Meanwhile, the latex agglutination test and CHROMagar culture accurately identified BORCoNS but not OS-MRCoNS. Conclusions: Finally, our findings imply that the recognition of methicillin resistance in CoNS requires a meticulous approach and that further research is needed to develop unified laboratory diagnostic algorithms to prevent the misreporting of borderline CoNS.

Background/Objectives: Surgical site infections are a serious public health concern, representing a significant burden on healthcare systems and society. Their occurrence is influenced by several factors, including patient demographics, healthcare facilities and the specific circumstances surrounding surgery. The use of prophylactic antibiotics in this context carries both potential benefits and risks. The aim of this study is to investigate potential risk factors that may adversely affect the development of SSIs, as well as to assess the appropriateness and adherence to perioperative antibiotic prophylaxis. Methods: This observational study was conducted from October 2023 to October 2024 at the University Hospital of Messina, Italy, a hospital performing both thoracic and vascular surgery. Data were collected using a questionnaire regarding socio-demographic data, risk factors, clinical and surgical data and details regarding the administration of antibiotics. Results: This study included 117 patients with an average age of 63 ± 12.36 SD years, 70.9% from the Thoracic Surgery Unit and 29.1% from the Vascular Surgery Unit. The most administered antibiotic was cefazolin, and antibiotic administration time was in compliance with the guidelines. Conclusions: Our data show that the implementation of evidence-based guidelines, healthcare professionals' education and correct antibiotic use can reduce the burden of SSIs by improving patient care.

Background/Objectives: The COVID-19 pandemic affected antimicrobial stewardship in healthcare, including Skilled Nursing Facilities (SNFs). This study aimed to (1) assess the appropriateness of antibiotic prescriptions for urinary tract infections (UTIs) and respiratory tract infections (RTIs) and identify predictors of inappropriate use; (2) analyze changes in prescribing practices relative to the pandemic's onset. Methods: A retrospective review of electronic medical records from a 300-bed SNF (March 2019-March 2021) identified suspected UTIs and RTIs based on laboratory tests and antibiotic requests. Antibiotic prescription appropriateness was defined by clinical and microbiological alignment with the McGeer criteria, which are standardized infection definitions for long-term care residents, for UTI and RTI. Logistic regression models identified predictors of inappropriate prescribing, and an interrupted time-series analysis (ITS) examined trends relative to the pandemic onset (11 March 2020) in Arizona. Results: Among 370 antibiotic prescriptions, 77% of UTI and 61% of RTI prescriptions were inappropriate per the McGeer criteria. Acute dysuria and increased urgency were associated with lower odds of inappropriate UTI prescribing. For RTIs, a positive COVID-19 test increased the odds of inappropriate prescribing, while fever and acute functional decline lowered them. UTI prescriptions and inappropriateness overall increased during the pandemic, but no significant ITS trends emerged. For RTIs, no significant changes in prescribing or inappropriateness relative to the pandemic were observed. Findings emphasize the need for robust antimicrobial stewardship during and after public health emergencies.

Background: Streptococcus sanguinis is a leading cause of infective endocarditis (IE), which causes diverse clinical symptoms and even death. Recurrence after treatment is a crucial problem in IE, possibly caused by the presence of "persister" cells, a small bacterial population that can survive antimicrobials. In this study, the residual risk for penicillin G (PCG) and gentamicin (GM), used for treating IE, to induce Streptococcus sanguinis persisters, was investigated. Methods: The bactericidal effects of PCG and GM on S. sanguinis were evaluated. Furthermore, we confirmed whether the S. sanguinis that survived following combination treatment with PCG and GM were persisters. The bactericidal effect of the combination of PCG and GM against S. sanguinis was measured after the addition of glucose or arginine. Results: Following 48 h of treatment with PCG (1600 μg/mL) and GM (64 μg/mL), S. sanguinis survived, albeit with a low bacterial count, indicating the presence of persisters. The addition of glucose or arginine to PCG and GM increased the bactericidal effect on residual persister cells and reduced the number of persister cells. Moreover, the addition of glucose at concentrations of 10 mg/mL or higher was substantially effective in achieving sterilization. Conclusions: Our findings demonstrate that persisters of S. sanguinis that survive antimicrobial treatment may make the treatment of IE challenging, and that combining antimicrobial treatment with glucose is effective for eliminating persisters of S. sanguinis. Taken together, these findings may facilitate the development of novel therapeutic strategies against IE caused by oral streptococcal infection.

Background/Objectives: Vancomycin is a reserve antibiotic that is frequently prescribed for central venous catheter (CVC)-associated infections in hemodialysis patients. Hemodialysis patients are very fragile patients and the presence of CVCs increases the risk of sepsis. We conducted a prospective study, evaluating the needs of changes in vancomycin dosing for treatment based on the use of the new 2020 vancomycin dosing guidelines, to increase drug safety (preventing subtherapeutic or supratherapeutic doses and offering therapeutic concentrations of the drug) in a particular group of patients with sepsis caused by catheter infections and being on intermittent hemodialysis. Methods: This prospective study included patients with sepsis caused by catheter infections and being on intermittent hemodialysis, treated with vancomycin, admitted in the nephrology department and intensive care unit (ICU). Vancomycin levels were adjusted according to the 2020 vancomycin guidelines. Results: In our study, nine (45%) patients had a vancomycin AUC between 400 and 600 mcg × h/mL, five (25%) patients had a subtherapeutic AUC, and six (30%) patients had a supratherapeutic AUC. It is important to mention that in 10 (50%) of the patients included in the study, the loading and maintenance doses mentioned in the protocol were respected, but 50% of them had a supratherapeutic AUC. We observed that a supratherapeutic AUC occurred when the loading dose was 1500 mg or 2000 mg, and in one case at 1000 mg with a low BMI. Conclusions: a therapeutic level of vancomycin can often be difficult to achieve because of different reasons, mainly in hemodialysis patients.

Background/Objectives: Excessive or inadequate use of antimicrobial drugs may lead to the emergence of resistant strains. For this reason, it is important to monitor consumption indicators to assess drugs' utilization over time. This study aimed to analyze the consumption of medically prescribed azole antifungal drugs in mainland Portugal from 2014 to 2023, focusing on those directed to genital infections: fluconazole, isoconazole, itraconazole, and sertaconazole. Methods: For each drug, the evaluated parameters were the total number of packages, number of packages per 1000 inhabitants, defined daily dose (DDD) per 1000 inhabitants per day, and total costs. For this purpose, we used data from community pharmacies' sales, which are available through INFARMED (the Portuguese national authority on medicines and health products). Results: Several trends emerged from data analysis. The COVID-19 pandemic negatively affected the consumption of all azole antifungal drugs included in this study. However, after 2020, fluconazole and sertaconazole consumption has been increasing. In the specific case of fluconazole, there was an increase in expenditure, although the total number of packages suffered a decrease over the 10-year study period. Additionally, the defined daily dose (DDD) per 1000 inhabitants per day for fluconazole and itraconazole was lower compared to estimates from the last available survey (2009). Conclusions: Although our findings represent a lesser pressure on fungi, further monitoring is needed to better understand the evolution of fluconazole and itraconazole consumption over time, particularly due to the trends observed in this study.

Background: In dogs, bacterial urinary tract infections are a frequent cause of antimicrobial prescription, increasing the risk of selecting antibiotic-resistant bacteria. This study analyzed resistance patterns, the presence of extended-spectrum β-lactamases (ESBLs) and biofilm-forming capacity in E. coli and K. pneumoniae previously isolated from urine samples collected from 133 selected dogs admitted to the Veterinary Teaching Hospital of Milan, Italy, in 2021 and 2023. Methods: The E. coli and K. pneumoniae isolates were bacteriologically and genetically analyzed. Results: Overall, 53/133 (39.8%) samples had a positive microbiological culture. Thirty-four E. coli/K. pneumoniae isolates were detected, accounting for 26.5% of the examined samples. The 34 isolates included 28 E. coli and 6 K. pneumoniae. Four (11.8%) were ESBL-producing bacteria, all supported by bla_CTX-M gene belonging to group 1. The K. pneumoniae isolates were significantly associated with ESBL production (p < 0.05). MIC analysis showed 11 (32.4%) multidrug-resistant isolates. Biofilm-forming capacity was observed in 23 (67.6%) isolates, regardless of bacterial species, including 20 weakly and 3 moderately adherent bacteria. All moderate biofilm producers were K. pneumoniae. Multidrug resistance (MDR) was significantly more present in strains with moderate biofilm-forming ability compared to strains with weak ability to form biofilm (p < 0.05). E. coli was confirmed as the most commonly identified urinary isolate in dogs. Conclusions: The high presence of ESBL producers and MDR in K. pneumoniae suggests mandatory in vitro susceptibility testing in the presence of this bacterium in dogs with UTI. The association of moderate biofilm production with MDR highlights the need for monitoring and surveillance of bacterial prevalence and resistance patterns of urinary isolates in dogs.

Background/Objectives: Meropenem-vaborbactam (MEV) and ceftazidime-avibactam (CZA) are active against "urgent threat" pathogens like carbapenem-resistant Enterobacterales (CRE). However, few studies have compared outcomes between them. Methods: To explore comparative outcomes of MEV vs. CZA, we conducted a multicenter retrospective cohort study of all adult hospitalized patients with a serious infection (sepsis, urinary tract infection [UTI], complicated intraabdominal [cIAI] infection, or pneumonia) within the PINC AI Database, 2019-2021. Descriptive statistics compared the two groups along demographic and clinical characteristics, and multiple regression derived adjusted outcomes. Results: Among 1,989,765 patients who met enrollment criteria, 455 received MEV and 2320 CZA. Compared to CZA, patients on MEV were more commonly Caucasian (68.1% vs. 63.6%, p = 0.032) or Hispanic (21.8% vs. 12.8%, p < 0.001). Their mean [SD] Charlson comorbidity scores did not differ (3.6 [2.5] vs. 3.5 [2.5], p = 0.403). The most common index infection in both groups was pneumonia, though it was less prevalent in the MEV- than the CZA-treated group (48.1% vs. 56.8%, p = 0.001). Fewer than one-third of all patients received the respective drug within 2 days of the onset of the index infection (30.6% MEV vs. 33.0% CZA, p = 0.313). Fewer patients on MEV than CZA required mechanical ventilation (35.0% vs. 41.4%, p = 0.010). MEV treatment was associated with lower adjusted mortality (17.0% [95% CI 13.6%, 20.3%] vs. 20.6% [95% CI 19.0%, 22.2%], p = 0.048) relative to CZA. Conclusions: In this cohort of hospitalized patients treated with either MEV or CZA for their infectious syndrome, MEV was associated with lower adjusted hospital mortality, although the confidence intervals around the values overlapped.

Background: The emergence of antibiotic-resistant bacteria, including Staphylococcus epidermidis, underscores the need for novel antimicrobial agents. Celastrol, a natural compound derived from the plants of the Celastraceae family, has demonstrated promising antibacterial and antibiofilm properties against various pathogens. Objectives: This study aims to evaluate the antibacterial effects, mechanism of action, and antibiofilm activity of celastrol against S. epidermidis, an emerging opportunistic pathogen. Methods: To investigate the mechanism of action of celastrol, its antibacterial activity was evaluated by determining the time-kill curves, assessing macromolecular synthesis, and analysing its impact on the stability and functionality of the bacterial cell membrane. Additionally, its effect on biofilm formation and disruption was examined. Results: Celastrol exhibited significant antibacterial activity with a minimal inhibitory concentration (MIC) of 0.31 μg/mL and minimal bactericidal concentration (MBC) of 15 μg/mL, which is superior to conventional antibiotics used as control. Time-kill assays revealed a concentration-dependent bactericidal effect, with a shift from bacteriostatic activity at lower concentrations to bactericidal and lytic effect at higher concentrations. Celastrol inhibited cell wall biosynthesis by blocking the incorporation of N-acetylglucosamine (NAG) into peptidoglycan. In contrast, the cytoplasmic membrane was only affected at higher concentrations of the compound or after prolonged exposure times. Additionally, celastrol was able to disrupt biofilm formation at concentrations of 0.9 μg/mL and to eradicate pre-formed biofilms at 7.5 μg/mL in S. epidermidis. Conclusions: Celastrol exhibits significant antibacterial and antibiofilm activities against S. epidermidis, with a primary action on cell wall synthesis. Its efficacy in disrupting the formation of biofilms and pre-formed biofilms suggests its potential as a therapeutic agent for infections caused by biofilm-forming S. epidermidis resistant to conventional treatments.

Background/Objectives: Periprosthetic joint infections (PJI) are difficult to treat due to biofilm formation on implant surfaces and the surrounding tissue, often requiring removal or exchange of prostheses along with long-lasting antibiotic treatment. Antiseptic irrigation during revision surgery might decrease bacterial biofilm load and thereby improve treatment success. This in vitro study investigated and compared the effect of five advanced wound irrigation solutions to reduce bacterial burden in the PJI microenvironment. Methods: We treated in vitro biofilms grown on titanium alloy implant discs with clinical bacterial strains isolated from patients with PJIs, as well as abscess communities in a plasma-supplemented collagen matrix. The biofilms were exposed for 1 min to the following wound irrigation solutions: Preventia^®, Prontosan^®, Granudacyn^®, ActiMaris^® forte ('Actimaris'), and Octenilin^®. We measured the bacterial reduction of these irrigation solutions compared to Ringer-Lactate and to the strong bactericidal but not approved Betaseptic solution. Additionally, ex vivo free-floating bacteria isolated directly from clinical sonication fluids were treated in the same way, and regrowth or lack of regrowth was recorded as the outcome. Results: Irrigation solutions demonstrated variable efficacy. The mean CFU log₁₀ reduction was as follows: Octenilin, 3.07, Preventia, 1.17, Actimaris, 1.11, Prontosan, 1.03, and Granudacyn, 0.61. For SACs, the reduction was: Actimaris, 8.27, Octenilin, 0.58, Prontosan, 0.56, Preventia, 0.35, and Granudacyn, 0.24. Conclusions: All solutions achieved complete bacterial eradication in all tested ex vivo sonication fluids, except Granudacyn, which was ineffective in 33% of the samples (2 out of 6). Advanced wound irrigation solutions have the potential to reduce bacterial burden in the PJI microenvironment during revision surgery. However, their efficacy varies depending on bacterial species, growth state, and the composition of the irrigation solution. This underscores the importance of considering these factors when developing future PJI-specific irrigation solutions.