Special Issue on Anti-Infectives: Pharmacoepidemiology and Clinical Pharmacology

The exchange of knowledge is fundamental to the progression of health sciences. Each peer-reviewed publication provides insights into various institutions’ clinical practices and medical evidence. Best practices and evidence-based medicine must be shared as they provide opportunities to generate new ideas, replicate, and validate results. In this Special Issue of Pharmacoepidemiology, notable publications have been highlighted, which include a meta-analysis, a review of medication toxicity, an analysis of non-traditional therapy for Clostridioides difficile, a report on septic arthritis, and a pharmacokinetic study.

Alanazi and colleagues aggregated data for a meta-analysis and systematic review of the impact of antibiotic de-escalation [1]. Their study aimed to address the gap in knowledge regarding the implications of antibiotic de-escalation in patients on antibiotic use, duration of hospital stays, mortality, and cost. Nine hundred and one studies were screened, and twenty-five studies met the inclusion criteria. Each study had to be in English, with outcomes including mortality, length of hospitalization, antibiotic consumption, or cost of hospitalization. The reviewed studies included a mixture of pediatric (seven) and adult (eighteen) patient populations. Most of the studies had a Newcastle–Ottawa Scale score of six to seven, with the remaining studies having a score of five. The studies included a mix of prospective and retrospective designs with a mixture of infection types, antibiotic types, and clinical settings. The results indicated a mortality risk ratio of 0.67 (CI: 0.52–0.86), and the length of stay risk ratio was −0.12 (CI: −0.23–0.00). Both of these results favored antibiotic de-escalation. The studies revealed mixed results on the impact of cost. This review demonstrates that, in many cases, using less intensive, narrow-spectrum antibiotics without compromising patient outcomes is possible.

COVID-19 has transitioned into an endemic problem. Remdesivir remains one of the treatment options for mild-to-moderate COVID-19 [2]. It is one of the few options available as an intravenous formulation. FakhariRavari and colleagues concisely reviewed remdesivir-associated hepatotoxicity in hospitalized patients with COVID-19 infections [3]. Hepatotoxicity was defined as the elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than five times the upper limit of normal. Sixteen studies were included in the review, with eleven being prospective or randomized controlled trials. FakhariRavari and colleagues highlighted the major trials (SIMPLE-2, ACTT-2, and ACTT-1) and conducted a systematic review/meta-analysis. The authors suggested that the overlapping clinical manifestations of remdesivir-induced liver toxicity and hepatotoxicity directly attributable to the viral infection require a more targeted evaluation, particularly in populations with pre-existing liver conditions. It is difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity; however, the summary of results suggests that remdesivir is likely safe regarding hepatotoxicity.

Clostridioides difficile infection (CDI) continues to be a healthcare burden in the US. The current treatment recommendation includes fidaxomicin and oral vancomycin. Limited evidence is available for treatments such as tigecycline beyond standard therapy. The utilization of non-traditional therapy for CDI is commonly associated with prior treatments, recurrent episodes, or complicated courses [4]. Johannesmeyer and colleagues evaluated adjunctive tigecycline to standard therapy to evaluate recovery rates [5]. Previous studies have revealed mixed results regarding utilizing tigecycline in CDI [6,7]. The results of this study were very similar to those of Philips and colleagues. No difference was observed in hospitalization duration, readmission rates, or clinical cure attainment at the time of hospital discharge between tigecycline and standard-of-care groups. The study did find that patients receiving tigecycline had higher rates of in-hospital mortality, 14.3% compared to no mortality in the standard-of-care group. This study highlights the importance of publishing in areas of limited clinical evidence without positive results, minimizing publication bias toward favorable results only. The results provide institutions and antimicrobial stewardship teams with an additional tool to promote appropriate antimicrobial use, especially in CDI.

There have been previous reports of off-labeled dalbavancin use in bacteremia and prosthetic joint infections [8,9]. The retrospective case report on dalbavancin use is similar to a proof-of-concept type of study in treating Enterococcus and Streptococcus pneumoniae bacteremia secondary to septic arthritis [10]. The report provides a detailed timeline for standard treatment, surgery, and the eventual decision on starting dalbavancin. One of the interesting aspects of the report was that the patient receiving therapy was morbidly obese, weighing 145 kg on admission, and the polymicrobial nature of the infection. This case report highlights the potential areas of future research with dalbavancin.

Eubank and colleagues conducted a multicenter, retrospective study evaluating vancomycin concentrations in stool from intravenous vancomycin exposure [11]. Vancomycin concentrations in the stool secondary to non-oral exposures have been documented previously [12]. In contrast to the previous study, Eubank and colleagues utilized previously collected stool samples as part of CDI detection prior to oral vancomycin therapy. All individuals in the study received intravenous vancomycin for at least 48 h, and at least one dose was given < 24 h before stool sample collection. Vancomycin stool concentrations were measured using HPLC. Nine percent (3/33) of the samples had detectable vancomycin levels ranging from 1.2 mcg/mL to 13.2 mcg/mL. This study highlighted that a short course of vancomycin can produce detectable levels. The results of this study challenge what we know about intravenous vancomycin excretion into the gastrointestinal tract. The implication of this study is the impact on the gut microbiome and the potential for resistance development in Enterococcus species or C. difficile.

The findings of these studies provide the tools we use to improve patient care and further health science. Nevertheless, it is insufficient just to have these tools. The dissemination of best practices and new ideas will help seed further research. This editorial provides examples of different perspectives on where knowledge gaps exist.