Antibiotics-Basel最新文献

Most surveillance studies in Saudi Arabia have been single-centered or did not use the gold standard broth microdilution (BMD) antimicrobial susceptibility test. This is the first study from Saudi Arabia to evaluate the resistance profiles of Acinetobacter baumannii by using BMD on a national level. Between November 2022 and April 2023, isolates from several infection sites were collected from seven hospitals in seven regions of Saudi Arabia. On testing days, BMD was done following Clinical Laboratory Standards Institute standards. Antibiotic susceptibility percentages and MIC₅₀ and MIC₉₀ were calculated. One hundred A. baumannii isolates were included. The highest susceptibility was to tigecycline (39%) and aminoglycosides (22-25%). The MIC₉₀ of all antibiotics were higher than the resistance breakpoint. All isolates (100%) were multidrug-resistant, of which 52% were classified as extensive-drug-resistant, and 42% were identified as pandrug-resistant. The isolates collected from the ear, peritoneal fluid, and the cerebrospinal fluid were all XDR, while 2/3 of the urine isolates (10/15; 66.7%), more than 1/2 of the skin/soft tissue and respiratory isolates (9/16; 56.3% and 22/43; 51.7%, respectively), and 3/8 (37.5%) of the blood isolates met this definition. Conversely, PDR isolates made up 5/8 of blood isolates (62.5%), 8/15 of body fluid isolates (57.14%), and 19/43 (44.2%) of respiratory isolates. A. baumannii showed a surprisingly high resistance to multiple commonly used antibiotics. Infection control policies and antimicrobial stewardship should be implemented by hospitals throughout the country to improve treatment, track resistance trends with local antibiograms, and prevent the development of resistant strains.

Background/Objectives: The management of urinary tract infections (UTIs) has become an increasingly challenging medical intervention. This study explores whether adoption of a precision medicine model could improve the management of acute uncomplicated pyelonephritis (uAPN) or complicated UTIs (cUTIs) compared with the standard of care approach, in hospitalized patients. Methods: From January 2022 to March 2024, all patients affected by uAPN or cUTIs and attending our urological institution were randomized to receive the following: antibiotic treatment according to guidelines and recommendations (standard of care group) or antibiotic treatment according to the precision medical model (intervention group). The main outcome measures were the rates of clinical success and the length of hospitalization. The time until switching to oral treatment was regarded as a secondary outcome measure. Results: Eighty-three patients were enrolled in the standard of care group, while seventy-nine patients were enrolled in the intervention group. While the overall clinical success rate was similar in the two groups (75 vs. 72; p = 0.97), a statistically significant difference was observed between the two groups in terms of length of hospitalization (8 days vs. 5 days; p = 0.03) and time to switch to oral treatment (96 h vs. 72 h; p = 0.04). A statistically significant difference was found between the two groups regarding the need to change antimicrobial therapy during hospitalization [12 out of 80 vs. 6 out of 77; p = 0.04]. Conclusions: Adoption of the precision medicine model appears as a valuable means to improve the management of patients with uAPN and cUTIs. By reducing the period of hospitalization and the time to switch to oral treatment, the precision medicine model also improves antimicrobial stewardship in the management of UTIs.

Background: Multi-drug-resistant Gram-negative bacteria producing metallo-β-lactamase are an increasing concern. Here, we described three cases of infection due to difficult-to-treat and drug-resistant P. aeruginosa producing metallo-β-lactamases, which were successfully treated with antibiotic combination of cefiderocol plus imipenem-relebactam, and reported on the molecular and epidemiological features of the isolates and the in vitro synergistic effects of different antibiotic combinations guiding antibiotic treatment. Patients and methods: Three P. aeruginosa strains were isolated from respiratory or blood cultures of three different patients. Minimum inhibitory concentrations breakpoints were interpreted according to EUCAST recommendations. Next-generation sequencing data were used for in silico identification of resistance genes and sequence types and for core genome multi-locus sequence typing analysis. The fractional inhibitory concentration index was performed as a measure of synergy of cefiderocol plus imipenem and imipenem-relebactam. Results: The three isolates exhibited different multi-drug-resistant and molecular profiles carrying blaIMP-13 (imipenemase metallo-β-lactamase-13) (isolates named Pse-1 and Pse-3) and blaVIM-2 (Verona integron-encoded metallo-β-lactamase-2) (isolate Pse-2). Typing showed that the isolates did not cluster and belonged to different sequence types. The E-test method showed the presence of synergy of cefiderocol in combination with imipenem-relebactam in the two P. aeruginosa isolates producing IMP-13 (Pse-1 and Pse-3). No synergy was observed in the isolate producing VIM-2 (Pse-2). Conclusions: Cefiderocol in association with imipenem-relebactam exhibited a synergistic effect against IMP-producing P. aeruginosa isolates. Further studies with a range of drugs and an expanded number of isolates are required to ascertain potential novel synergistic associations and the clinical utility of the fractional inhibitory concentration index.

Introduction: Antibiotic resistance is a major public health problem in Europe. Most antibiotics are sold only by prescription in Poland, and it is mainly up to physicians to decide whether to start antibiotic treatment. Therefore, we analyzed the factors influencing the prescribing of antibiotics for upper respiratory tract infections by primary care physicians in Poland, attitudes toward antibiotic resistance, and knowledge of the principles of antibiotic use. Methods: We conducted a CAWI (Computer-Assisted Web Interview) survey, carried out using a proprietary survey distributed online. Results: A total of 528 doctors participated in the study. The result of the physical examination and additional tests, as well as the recommendations of scientific societies are the most important in deciding whether to start antibiotic therapy. Patient pressure (p < 0.011) and workload (p = 0.021) significantly influenced the decision to prescribe an antibiotic among primary care physicians and physicians in the course of specialization, who fear of legal consequences (p < 0.001). The habits of other physicians (p < 0.001) working at the same facility appeared to be additionally important. Conclusions: The decision to implement antibiotic therapy in upper respiratory tract infections is influenced by several factors that depend on the doctor (including place of work and seniority) and the patient (clinical symptoms, expectation of antibiotic prescription). The physician's level of knowledge contributes to reducing antibiotic prescribing. Considering the factors associated with the level of knowledge and awareness, together with a high prevalence of self-medication with antibiotics in Polish population, there is a strong need to design educational interventions aimed at reducing inappropriate antibiotic prescribing and preventing antibiotic resistance in Poland.

Background/Objectives: Antimicrobial resistance (AMR) is a global problem with antibiotic consumption considered a key modifiable factor for the development of AMR. Long-term care (LTC) facilities have been identified as potential reservoirs for Escherichia coli (E. coli) resistance due to high rates of urinary tract infection (UTI) and high levels of antibiotic consumption among residents. However, while the relationship between these two factors is well accepted, little is known about the possible temporal relationship between these. This study explores trends in E. coli resistance and antibiotic consumption in LTC focused on potential temporal relationships between antibiotic utilization and AMR.

Methods: A retrospective, longitudinal, and ecological analysis was conducted between 31 May 2016 and 31 December 2018. The primary outcomes were the monthly prevalence of E. coli AMR in urine isolates and the monthly percentage of residents using an antibiotic recommended for the management of UTI in national treatment guidelines (amoxicillin, amoxicillin with clavulanic acid, cefalexin, norfloxacin, and trimethoprim).

Results: During the study period, 10,835 urine E. coli isolates were tested, and 3219 residents received one or more medicines and were included in the medicines dataset. Over one-quarter were resistant to at least one of the target antibiotics (23.3%). For most antibiotics, the temporal relationship between AMR and antibiotic utilization was unclear; however, potential patterns were observed for both trimethoprim and amoxicillin with clavulanic acid. Trimethoprim showed a temporal decrease in both AMR and utilization, while amoxicillin with clavulanic acid showed a lag time of approximately four months between utilization and resistance.

Conclusions: The dynamic nature of AMR demonstrated in this study highlights the need for more up-to-date local surveillance to inform antibiotic choice in this setting.

The rapid rise of antibiotic resistance has become a global health crisis, necessitating the development of innovative strategies to combat multidrug-resistant (MDR) pathogens. Nanomaterials have emerged as promising tools in this fight, offering unique physicochemical properties that enhance antibiotic efficacy, overcome resistance mechanisms, and provide alternative therapeutic approaches. This review explores the diverse nanomaterial-based strategies used to combat antibiotic resistance, focusing on their mechanisms of action and practical applications. Nanomaterials such as metal nanoparticles, carbon-based nanomaterials, and polymeric nanostructures exhibit antibacterial properties through various pathways, including the generation of reactive oxygen species (ROS), disruption of bacterial membranes, and enhancement of antibiotic delivery. Additionally, the ability of nanomaterials to bypass traditional resistance mechanisms, such as biofilm formation and efflux pumps, has been demonstrated in numerous studies. This review also discusses the synergistic effects observed when nanomaterials are combined with conventional antibiotics, leading to increased bacterial susceptibility and reduced required dosages. By highlighting the recent advancements and clinical applications of nanomaterial-antibiotic combinations, this paper provides a comprehensive overview of how nanomaterials are reshaping the future of antibacterial therapies. Future research directions and challenges, including toxicity and scalability, are also addressed to guide the development of safer, more effective nanomaterial-based antibacterial treatments.

Background/Objectives: Periprosthetic joint infections (PJIs) are feared complications in arthroplasty and are associated with an increased mortality rate. PJI prevention is of paramount importance since treatment is difficult. In case of an infection, it is crucial to diagnose it at an early stage in order to initiate adequate therapy. The Musculoskeletal Infection Society (MSIS) proposed a catalog of different major and minor diagnostic criteria in 2011 to define a PJI. They were adapted in the following years. One of these criteria is the blood level of C-reactive protein (CRP). CRP is a non-specific acute-phase protein that also increases in response to various non-infectious inflammatory responses. CRP is also routinely obtained prior to total hip arthroplasty (THA) to screen for possible contraindications for arthroplasty such as an acute infection. The validity of this approach has rarely been investigated. The aim of this study was to evaluate the diagnostic value of perioperative CRP in patients receiving a THA. Methods: A total of 239 patients were included in this study and retrospectively analyzed. CRP values were obtained preoperatively and three values postoperatively. Sensitivity, specificity, area under the curve (AUC) and optimal thresholds were calculated. Results: In the whole group, 10 patients developed a PJI. No significance was demonstrated between patients without and with later PJI in terms of preoperative CRP (p = 0.182), postoperative CRP (p = 0.167), relative CRP increase (p = 0.684) and respective CRP differences (p = 0.456). We were not able to find cut-off values with adequate sensitivity and specificity. Conclusions: Perioperative CRP values do not seem to be helpful in predicting further PJI. Rather, they should be used as a screening tool to detect ongoing infections in the individual patient prior to THA. This trial should encourage studies with more statistical power due to the small effect sizes.

Background/Objectives: Studies show that SNPs in ABCB1 rs2032582 and SLCO1B1 rs4149015 affect the PK profile of moxifloxacin, a key drug for MDR-TB. This study aimed to assess the genotype frequencies of ABCB1 rs2032582 and SLCO1B1 rs4149015; describe moxifloxacin AUC_0-24 and C_max; and evaluate the association between genotype variations and moxifloxacin AUC_0-24 and C_max, corrected for the effect of other determinants in MDR-TB patients in Indonesia. Methods: The genotypes were identified using DNA sequencing. Plasma samples for PK analysis were collected at either two or four timepoints post-dose, at steady state. AUC_0-24 values were assessed with a limited sampling formula. A multivariate linear regression analysis identified the determinants for moxifloxacin AUC_0-24 and C_max. Results: We recruited 204 MDR-TB patients for PG analysis, with 80 providing PK samples. The majority of the ABCB1 and SLCO1B1 genotypes were wildtype (GG), 41.7% and 93.6%, respectively. The geometric mean AUC_0-24 for moxifloxacin was 78.6 mg·h/L and that for C_max was 6.1 mg/L. No statistically significant difference in exposure to moxifloxacin could be shown between the genotypes. Sex, age, and dose in mg/kg/body weight were significant determinants of the AUC_0-24 of moxifloxacin. Conclusions: The major genotype of ABCB1 rs2032582 and SLCO1B1 rs4149015 was wildtype, and the exposure to moxifloxacin was high but not related to the studied genotype in an Indonesian population.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a common adverse event following antiresorptive treatment, leading to chronic inflammation and exposed, necrotic bone surfaces in the jawbone. There is an increasing recognition of the role of compositional changes in the colonizing members of the oral microbiota implicated in triggering and/or maintaining MRONJ. The aim of our study was to characterize the culturable and non-culturable microbiota-with particular focus on Actinomyces spp. and Actinomyces-like organisms (ALOs)-from surgically removed bone samples of MRONJ patients and healthy control subjects. Methods: n = 35 patients (median age: 70 years) in various stages of MRONJ, with a history of receiving oral or intravenous antiresorptive treatment were included in the study. The controls (n = 35; median age: 35 years) consisted of otherwise healthy individuals undergoing tooth extraction. Traditional, quantitative, aerobic, and anaerobic culture, and Actinomyces-specific PCR was performed for all bone samples from patients and controls, while microbiome analyses-based on 16S rRNA sequencing-were carried out in 5-5 randomly selected samples. Mann-Whitney U test, Wilcoxon rank sum test (alpha diversity), and PERMANOVA analysis (beta diversity) were performed. Results: In MRONJ samples, 185 anaerobic isolates, corresponding to 65 different species were identified (vs. 72 isolates, corresponding to 27 different species in the control group). The detection of Actinomyces spp. and ALOs was more common in MRONJ bone samples, based on traditional culture (65.7% vs. 17.1%; p < 0.001) and PCR (82.9% vs. 37.1%; p < 0.001), respectively. The isolation of Fusobacterium spp. (22 vs. 7; p = 0.001), Prevotella spp. (22 vs. 6; p = 0.034), and Gram-positive anaerobic cocci (GPAC) (30 vs. 9; p = 0.016) was significantly more common in MRONJ patient samples. The microbiota of the controls' bone samples were characterized by a considerable dominance of Streptococcus spp. and Veillonella spp, while the bacterial abundance rates were substantially more heterogeneous in MRONJ bone samples. Notable differences were not observed among the samples related to the abundance of Actinomyces in the bone microbiota. Conclusions: According to the "infection hypothesis", alterations in the oral microbiome-with Actinomyces and ALOs being the most relevant-may play a key role in the development, aggravation, and progression of MRONJ. The timely detection of Actinomyces in necrotic bone is crucial, as it has important therapeutic implications.