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We evaluated the in vivo efficacy of humanized exposures of cefiderocol, a novel siderophore cephalosporin, against a test panel of P. aeruginosa (PSA) previously shown to develop resistance to 2 preclinical candidate siderophores (MB-1 and SMC-3176). In the thigh infection model, the PSA bacterial density in untreated controls grew from 5.54 ± 0.23 to 8.68 ± 0.57 log₁₀ CFU over 24 h. The humanized cefiderocol exposure resulted in >1 log₁₀ CFU reduction in all 8 isolates, while MB-1 and SMC-3176 exhibited variable activity similar to that previously reported. Humanized exposures of cefepime and levofloxacin, acting as positive antimicrobial controls displayed activity consistent with that of the bacterial phenotypic susceptibility profiles. Cefiderocol manifested in vivo efficacy against all PSA isolates including those resistant to cefepime and levofloxacin in contrast to its predecessor siderophore compounds. These preclinical data are supportive of further evaluation of cefiderocol in the treatment of P. aeruginosa.

Due to resistance and scarcity of treatment options, nosocomial Acinetobacter baumannii infections are associated with significant fatality rates. We investigated the factors contributing to infection-related deaths to develop tailored stewardship interventions that could reduce these high mortality rates. We reviewed the medical records of adult inpatients with A. baumannii infections over two years. Patient demographics and clinical data were collected and statistically analyzed. The study included 321 patients with positive A. baumannii microbiological cultures, with respiratory infections accounting for 58.6%, soft tissues 29.3%, bacteremia 8.6%, urine 2.1%, and others 1.4%. The study population’s median (IQR) age was 62.6 (38.9–94.9) years, and hospital stay was 20 (9.5–40) days. Statistical analysis revealed that various risk factors contribute significantly to high in-hospital all-cause mortality (44%), as well as 14-day and 28-day mortality rates. Deaths increased by a factor of 1.04 with every additional year of age (p = 0.000), admission to the critical care unit (p = 0.000, OR: 2.86), and patients admitted with an infectious diagnosis had nearly three times the mortality rate as those admitted with other diagnoses (p = 0.000, OR: 3.12). Male gender (p < 0.001, OR: 2.14), any comorbid conditions (p = 0.000, OR: 5.29), prolonged hospitalization (>7 days) (p = 0.023, OR: 1.98), and hospital acquisition of infection (p = 0.027, OR: 1.68) were among the most significant predictors of mortality. All variables were investigated for their impact on all-cause, 14-day, and 28-day mortality rates. Improving multidisciplinary infection control practices, regular disinfection of patient care equipment, and optimal intubation practice that avoids unnecessary intubation are necessary interventions to reduce infection-related mortality rates. Better antibiotic selection and de-escalation, shorter hospital stays whenever possible, prompt medical stabilization of comorbid conditions, and fewer unnecessary admissions to critical care units will all lead to improved outcomes.

The majority of patients with influenza RTI received antibiotics on admission, and 34.5% were inappropriately continued on antibiotics without evidence of bacterial infection, which led to increased LOS, loss of net revenue, and no improvement in outcome. Thus, stewardship initiatives aimed at this population are warranted.

Catheter-related blood stream infections comprise a major concern in hemodialysis patients, leading to increased mortality, morbidity, and cost of treatment. Prompt appropriate systemic antibiotics treatment, which includes administration of appropriate systemic antibiotics and, frequently, catheter removal and replacement, is warranted. However, in hemodialysis patients, repeated catheter insertions may cause central vein stenosis and thrombosis which limits the future availability of hemodialysis access. Lock solutions containing antibiotics and anticoagulants, instilled directly into the catheter lumen after each dialysis, have been successfully utilized for catheter salvage but higher rates of recurrence and complications were observed in infections resulting from staphylococcal species. We report several cases of catheter salvage using antibiotic lock solution in staphylococcal bacteremia with the purpose of stimulating the interest in randomized clinical trials. Evaluating the risk and benefits of catheter salvage in this patient subset in light of optimized systemic antibiotic dosing, improved lock solution use, and multidisciplinary involvement, balanced with the critical need to prevent unnecessary vascular trauma, is of great importance.

Background: Increasing rate of resistant infections is a challenge to healthcare negatively impacting therapeutic and financial outcomes. Targeted antimicrobial stewardship interventions are needed to counteract this global crisis. On large scale, we sought to identify the prevalence of resistant pathogens and their susceptibility pattern in Northern Oman. Material and method: Retrospective analysis of all isolates processed by Suhar Hospital microbiology laboratory between Jan1st, 2016 and Dec31st, 2017. Organism identification, susceptibility and phenotyping were performed following CLSI standards and duplicate isolates were excluded. Pertinent microbiological data were collected and analyzed. Results: Of 15,733 samples included, Gram-negative bacteria predominate by 67.76%, Gram-positive (29%) and Candida species (2.63%). Frequently isolated Gram-negative bacteria were Escherichia coli (32.39%), Pseudomonas aeruginosa (22.16%), Klebsiellapneumoniae (19.97%) and Acinetobacter baumannii (5.22%), there was virtually no resistance to colistin and tigecycline, while a growing resistance toward ciprofloxacin and meropenem was observed. Resistant E. coli and K. pneumoniae were isolated from bloodstream infection (12%). While Gram-positives were MSSA (27.23%), Streptococcus agalactiae (25.36%), MRSA (16.10%) and CoNS (12.1 %), they were almost universally susceptible to daptomycin and linezolid with low resistance (8~20%) to clindamycin. Approximately, 50% of Staphylococci (MRSA and CoNS) required vancomycin treatment. Conclusion: Study findings should guide targeted stewardship interventions to optimize antibiotic prescriptions. Empirical treatment options should be revised, drug-bug match therapy instituted promptly and newer agents considered. Prescribing restriction of formulary antimicrobials that still retain their activity towards bugslike colistin, linezolid and tigecycline-is a mandatory action. Review empiric use of ciprofloxacin and meropenem to counteract growing resistance.

Background: The approved dosing of ertapenem in patients with chronic kidney disease stage 5 utilizing dialysis (CKD-5D) is 0.5 g intravenous daily. Several reports associated this dosing strategy with neurotoxicity. Objective: The purpose of this study is to identify the incidence of neurotoxicity in this population and the risk factors associated with this toxicity. The secondary objective was to review the literature and discuss a safer/cost-effective dosing strategy based on available data. Methods: A retrospective study was conducted screening all patients who received ertapenem and hemodialysis at our quaternary hospital between May 2015 and March 2019. Patients’ demographics, comorbidities, concomitant drugs (known to induce neurotoxicity), and seizure history were collected. Results: A total of 99 eligible patients were identified; 10 of them (10%) developed neurotoxicity. The patients who developed neurotoxicity were all male; mean age was 74 ± 9 years as compared with 68.9 ± 13 years in the sample. Bivariate relationships between all predictors and the seizures (dichotomously coded) were estimated to investigate the risk factors. The following were the significant predictors of seizures: male sex (17%; P = 0.014), dementia (27%; P = 0.012), and concomitant use of β-lactams, aminoglycosides, or fluoroquinolones (19.6%; P = 0.042). Conclusion and Relevance: The currently approved ertapenem dose imposes a risk of developing neurotoxicity in patients with CKD-5D. Utilizing the published data in this population, alternative post-dialysis dosing strategies administered through dialysis access such as 1 g loading dose, followed by either 0.5 g (for the 48 hours interdialytic time) or 1 g (for the 72 hours interdialytic time) might warrant further investigation for efficacy and safety.