Objective: To describe weight changes with integrase strand transfer inhibitor (INSTI) therapy. Data Sources: A literature search was performed (through December 15, 2021) using the PubMed and CINAHL databases using the search terms: “integrase inhibitors,” “integrase strand transfer inhibitors,” and “weight.” Study Selection and Data Extraction: Studies were included that provided relevant information on weight or body mass index (BMI) changes on INSTI therapy. Controlled or observational studies comparing different INSTI therapies or compared INSTI therapy to another class of antiretroviral therapy were included. Data Synthesis: Forty-three articles met criteria for inclusion, and data are presented. Although some trials have observed similar weight gains between INSTI, protease inhibitor, and non-nucleoside inhibitor therapies, the increase appears to be greater with INSTI therapy, particularly during initiation of therapy. Risk factors for weight gain with INSTI therapy include female gender, lower CD4 count, and combined use of tenofovir alafenamide. Within the INSTI class, dolutegravir and bictegravir appear to have the greatest propensity for weight gain. Relevance to Patient Care and Clinical Practice: INSTI-based therapies are the preferred initial management of HIV infection. Discerning the factors contributing to weight changes on INSTI therapy and risks of associated health-related outcomes is important to both the management of weight gain and HIV medical management. Conclusions: Within the INSTI class, dolutegravir and bictegravir may be associated with the greatest risk for weight gain particularly when combined with tenofovir alafenamide. Further research is needed to determine mechanisms for observed weight changes and any contributions to clinically significant metabolic and cardiovascular adverse outcomes associated with INSTI therapy.

Objective: To determine the incidence with which a vancomycin dosing regimen of 15 mg/kg per dose every 6 hours achieves steady-state trough concentrations of 15 to 20 mg/L in pediatric patients with complicated infections. Methods: We performed a retrospective chart review for patients admitted to our children’s hospital between July 1, 2009, and June 30, 2011. Patients were included if they were between 1 month and 18 years of age, had at least 1 steady-state vancomycin trough obtained, received an initial vancomycin dose of 15 mg/kg per dose every 6 hours, and were being treated for a diagnosis of meningitis, pneumonia, osteomyelitis, bacteremia/sepsis, or endocarditis. Results: Seventy-four patients were enrolled, mean age of 4.2 ± 3.9 years and weight of 17.0 ± 11.2 kg. Five (6.8%) patients obtained an initial trough of 15 to 20 mg/L. Patients between 1.0 and 5.9 years of age were significantly less likely to achieve an initial trough of 15 to 20 mg/L compared with other age groups evaluated (P = .041). Thirty-four patients with initial subtherapeutic troughs received a dose adjustment and a follow-up vancomycin trough. Of these patients, 15 (44.1%) achieved a trough between 15 and 20 mg/L. The median dose for patients achieving a therapeutic trough at any point during the study was 80 mg/kg per day. Conclusions: A vancomycin dosing regimen of 15 mg/kg per dose every 6 hours is not likely to achieve a trough concentration of 15 to 20 mg/L in pediatric patients with complicated infections. An initial regimen of 80 mg/kg per day for these patients may be more likely to result in therapeutic steady-state concentrations of vancomycin.

Objective: To evaluate the existing data regarding the use of cranberry products for the prevention of urinary tract infections (UTIs) in pediatric patients. Data Sources: A literature search of Medline databases from 1966 to June 2015 was conducted. Study Selection and Data Extraction: The databases were searched using the terms “pediatrics,” “children,” “cranberry,” “cranberry juice,” and “urinary tract infections.” The identified trials were then searched for additional references applicable to this topic. Data Synthesis: A total of 8 clinical trials were identified that examined the use of cranberry products, mostly juice, for the prevention of UTIs in children. Three trials examined the use in otherwise healthy children. Five trials examined the use in pediatric patients with underlying urogenital abnormalities of which 2 compared cranberry to antibiotics. In healthy pediatric patients, cranberry use was associated with a reduction in the overall number of UTIs and a decrease in the number of antibiotic days per year for UTI treatment. In patients with urogenital abnormalities, results were conflicting, with some studies showing no reduction in UTIs compared with placebo, but others demonstrating a significant reduction. However, cranberry products had similar efficacy when compared with both cefaclor and trimethoprim. All studies used a wide variety of doses and frequencies of cranberry, making specific product recommendations difficult. Conclusions: Cranberry appears effective for the prevention of UTIs in otherwise healthy children and is at least as effective as antibiotics in children with underlying urogenital abnormalities. However, recommendations for cranberry dosing and frequency cannot be confidently made at this time. Larger, well-designed trials are recommended.

Objective: Review the pharmacology, pharmacokinetics, efficacy, safety, and role of long-acting injectable cabotegravir (CAB-LA) in HIV preexposure prophylaxis (PrEP). Data Sources: A literature search was performed using PubMed and Google Scholar (2012 to April 2022) with the search terms cabotegravir, preexposure prophylaxis, and PrEP. Other resources included abstracts presented at recent conferences, the manufacturer’s Web site, prescribing information, and review articles. Study Selection and Data Extraction: All English-language articles of studies assessing the efficacy and safety of CAB-LA for PrEP were included. Data Synthesis: CAB-LA is the first long-acting injectable therapy approved for HIV-1 PrEP in both men and women. It is a suspension given intramuscularly every other month. CAB-LA has been shown to be more effective than daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV-1 infection among high-risk individuals. Two phase 3 trials were stopped early on the basis of superior efficacy of CAB-LA. The most common adverse effects were injection site reactions (ISRs), although they tended to decrease over time, and few participants in clinical trials discontinued use due to ISRs. Relevance to Patient Care and Clinical Practice: CAB-LA may be particularly useful for individuals with known adherence problems to oral therapy, those with renal impairment, and those with decreased bone mineral density. However, CAB-LA is more expensive than generic TDF/FTC and may be associated with weight gain. Conclusions: CAB-LA is the first long-acting injectable agent for HIV PrEP. It is more effective than oral TDF/FTC, is well-tolerated aside from ISRs, and has few clinically significant drug-drug interactions.

Background: Ceftriaxone is a third-generation cephalosporin commonly utilized as an empiric antibiotic treatment option in the emergency department (ED). Overuse can lead to decreased susceptibility and emergence of multidrug-resistant pathogens, increased costs, and unnecessary adverse effects. Objective: The purpose of this project was to determine the appropriateness of ceftriaxone usage in the ED of a veteran’s health care system. Methods: This retrospective chart review included all veterans who received at least one dose of ceftriaxone in the ED between June 1, 2014, and June 1, 2015. The primary outcome was the percentage of appropriate ceftriaxone use. Usage appropriateness was determined on a case-by-case basis by examining current published guidelines and local recommendations based on the institutional antibiogram. Results: Ceftriaxone was prescribed for a wide variety of indications and was determined to be inappropriately prescribed in 164 patients (53%). The most common reason for inappropriate prescribing was lack of a first-line indication for ceftriaxone (64%). Only 120 patients (38.5%) exhibited systemic signs of infection based on vital signs and laboratory parameters, and 25 patients (8%) likely did not require antibiotic therapy at all. Conclusions: Ceftriaxone was used inappropriately in more than half of the patients who received the drug in the ED. The literature on the prescribing habits for ceftriaxone is limited in the United States, but these results are similar to studies conducted in other countries. Attempts should be made to educate prescribers on appropriate indications for the use of ceftriaxone.

Clostridioides difficile infections (CDIs), and particularly recurrent infections, cause a significant burden on the health-care system. Bezlotoxumab is a new agent for the prevention of recurrent CDIs that has shown strong efficacy and high tolerability in clinical trials. The purpose of this review is to evaluate the published literature for bezlotoxumab, with a focus on literature published since the release of the 2021 focused update to the CDI treatment guidelines. A Medline/PubMed search for “bezlotoxumab” was conducted, resulting in 152 articles. Seventeen studies are included in this review, after excluding non-English-language papers, phase I and II trials, and review articles. Studies published since the 2021 focused update support the recommendations in those guidelines. Furthermore, real-world studies have shown similar results to larger clinical trials. Those with more risk factors for recurrent CDI appear to benefit most from bezlotoxumab. Currently, there are no data to support the use of bezlotoxumab outside current guideline recommendations, but future trials may build on the data seen in real-world studies to further elucidate the place in therapy for bezlotoxumab.