Anti-Infectives: Pharmacoepidemiology and Clinical Pharmacology

Severe acute respiratory syndrome coronavirus 2 has infected millions of people, but about 20% of infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus and it is associated with liver injury and other complications, leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for the treatment of hospitalized patients with COVID-19 to improve the time to recovery, reduce the duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than five times the upper limit of normal in hospitalized patients with COVID-19, but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir, and a 5-day course of remdesivir seems to be safe in regard to hepatotoxicity. Full article

Dalbavancin, a semi-synthetic lipoglycopeptide with an extended half-life that allows for weekly dosing, is currently approved for the treatment of bacterial skin and soft tissue infections caused by susceptible gram-positive organisms. This case report discusses the successful treatment of septic arthritis with dalbavancin in a 38-year-old obese male. Septic arthritis, commonly caused by Staphylococcus aureus and Streptococcus species, was diagnosed in this patient following a mechanical fall that led to worsening shoulder pain. Given the patient’s morbid obesity and concerns about antibiotic penetration, dalbavancin 1500 mg IV biweekly was chosen for its extended half-life and ease of administration. This case underscores dalbavancin’s efficacy in managing septic arthritis in obese patients, offering a convenient alternative to traditional therapies that require a peripherally inserted central catheter (PICC line), frequent dosing, therapeutic monitoring, and prolonged hospital stays. Despite its higher cost, dalbavancin’s advantages include reduced need for PICC lines, additional staff and resources to monitor therapeutic drug levels, and fewer complications, which can offset some expenses. To our knowledge, this is the first documented case investigating the use of dalbavancin for enterococcal septic arthritis with a biweekly dosing regimen. Full article

Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea in the United States. Tigecycline has been proposed as a potential treatment for CDI, though limited clinical data exist to support this practice. The objective of this study was to determine if the provision of tigecycline provides a clinically meaningful benefit to inpatients with CDI. This study was a retrospective chart review enrolling inpatients receiving treatment for CDI. Patients were divided into cohorts depending on whether they received a standard antibiotic therapy regimen for CDI or an antibiotic treatment regimen that included tigecycline. The primary outcome was clinical recovery at the time of hospital discharge. A total of 39 and 22 patients were included in the standard antibiotic therapy and tigecycline groups, respectively. ATLAS (Age, Treatment, Leukocyte, Albumin, Serum creatinine) scores at the time of CDI diagnosis were similar between the two groups, though patients in the tigecycline groups were more likely to represent a recurrent episode of CDI. There was no difference in the rate of clinical recovery at the time of hospital discharge between the standard antibiotic therapy and tigecycline groups (38.5% vs. 36.4%, p = 0.8710). These data do not support the routine use of tigecycline for the treatment of CDI, though interpretation is limited due to baseline differences between groups and the retrospective, observational nature of this study. Full article

Overuse and misuse of antibiotics have led to the emergence of antibiotic-resistant bacteria and pose a significant threat due to adverse drug reactions, increased healthcare costs, and poor patient outcomes. Antibiotic stewardship programs, including antibiotic de-escalation, aim to optimize antibiotic use and to reduce the development of antibiotic resistance. This systematic review and meta-analysis aim to fill the gap by analyzing the current literature on the implications of antibiotic de-escalation in patients on antibiotic use, duration of hospital stay, mortality, and cost; to update clinical practice recommendations for the proper use of antibiotics; and to offer insightful information about the efficacy of antibiotic de-escalation. Based on the PRISMA 2020 recommendations, a comprehensive literature search was conducted using electronic databases and reference lists of identified studies. Eligible studies were published in English, conducted in humans, and evaluated the impact of antibiotic de-escalation on antibiotic consumption, length of hospitalization, mortality, or cost in hospitalized adult patients. Data were extracted using a standardized form, and the quality of included studies was assessed using the Newcastle–Ottawa Scale. The data from 25 studies were pooled and analyzed using the Revman-5 software, and statistical heterogeneity was evaluated using a chi-square test and I2 statistics. Among the total studies, seven studies were conducted in pediatric patients and the remaining studies were conducted in adults. The studies showed a wide range of de-escalation rates, with most studies reporting a rate above 50%. In some studies, de-escalation was associated with a decrease in antimicrobial utilization and mean length of stay, but the impact on overall cost was mixed. Our pooled analysis for mortality reported that a significant difference was observed between the de-escalation group and the non-de-escalation group in a random effect model (RR = 0.67, 95% CI 0.52–0.86, p = 0.001). The results suggest that de-escalation therapy can be applied in different healthcare settings and patient populations. However, the de-escalation rate varied depending on the study population and definition of de-escalation. Despite this variation, the results of this systematic review support the importance of de-escalation as a strategy to optimize antibiotic therapy and to reduce the development of subsequent antibiotic resistance. Further studies are needed to evaluate the impact of de-escalation on patient outcomes and to standardize the definition of de-escalation to allow for better comparison of studies. Full article

Vancomycin is not appreciably passaged via the colonic membrane to the gastrointestinal (GI) tract in persons with an intact gut epithelium due to its large chemical structure. However; hospitalized patients with diarrhea often have a disrupted GI tract. The aim of this study was to determine the frequency of detectable vancomycin concentrations in the stool of patients with antibiotic-associated diarrhea receiving IV vancomycin. This was a multicenter cohort study of hospitalized patients with stool samples collected for Clostridioides difficile testing. Leftover stool samples were collected from patients who had received at least 3 days of IV vancomycin. Fecal vancomycin was quantified by high-performance liquid chromatography. The study cohort included 33 unique patients, majority female (54.5%) aged 60 years (range 23–84). Eighteen of thirty-three patients (54.5%) tested positive for C. difficile toxins. The average duration of systemic vancomycin administration prior to stool collection was 3.5 (range 2–15) days. Three of 33 (9%) stool samples had a detectable vancomycin concentration (range 1.2–13.2 mcg/mL). These concentrations may promote the development of vancomycin-resistant Enterococcus or van mutations in C. difficile, leading to vancomycin resistance. Further studies on implications are warranted. Full article