Significant Publications on Infectious Diseases Pharmacotherapy in 2019.

PURPOSE: To provide a summary of the most prominent peer-reviewed infectious diseases (ID) pharmacotherapy and Human Immunodeficiency Virus (HIV)-related articles published in 2019. SUMMARY: Houston Infectious Diseases Network (HIDN) members were asked to nominate articles that they believed were most influential within the ID and HIV pharmacotherapy science communities. A total of 48 general ID and 6 HIV-related articles were nominated. Following nominations, an online survey was distributed via e-mail to Society of Infectious Diseases Pharmacists (SIDP) members, with a total of 156 and 54 members voting for general ID and HIV-related articles, respectively. The results of this survey were ranked to determine the top 10 general ID and top HIV articles. The top articles were then summarized by HIDN members, including residents, fellows, and clinical pharmacists. CONCLUSION: This review covers many of the most influential ID articles published in 2019, including 3 practice guideline updates. Due to the high rate of ID literature published each year, this review continues to help summarize these articles for the ID community, allowing clinicians to remain up-to-date on practice-changing publications in ID and HIV pharmacotherapy.

Outcomes of empiric aminoglycoside monotherapy for Pseudomonas aeruginosa bacteremia.

We evaluated 30-day mortality in patients with Pseudomonas aeruginosa bacteremia. There was no significant difference in mortality among patients who received functional aminoglycoside monotherapy versus inappropriate empiric therapy. Among patients given appropriate empiric therapy, functional aminoglycoside monotherapy was associated with less favorable outcomes compared to beta-lactam monotherapy.

Population Pharmacokinetics of Polymyxin B.

Polymyxin B is used as a last treatment resort for multidrug-resistant Gram-negative bacterial infections. The objectives of this study were to examine the population pharmacokinetics of polymyxin B and investigate factor(s) influencing pharmacokinetic variability. Four serial blood samples each were collected from 35 adult patients at steady state. The concentrations of individual polymyxin B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and combined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variables were investigated as potential covariates for clearance and volume of distribution (Vd ) using linear regression analysis. A one-compartment model fit to the data satisfactorily (r2 = 0.96). The best-fit mean ± SD for clearance and Vd were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to be a statistically significant covariate of clearance, but the magnitude was deemed clinically insignificant.

Role of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity.

Despite dose-limiting nephrotoxic potentials, polymyxin B has reemerged as the last line of therapy against multidrug-resistant Gram-negative bacterial infections. However, the handling of polymyxin B by the kidneys is still not thoroughly understood. The objectives of this study were to evaluate the impact of renal polymyxin B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225 to 250 g) were divided into three dosing groups, and polymyxin B was administered (5 mg/kg, 10 mg/kg, and 20 mg/kg) subcutaneously once daily. The onset of nephrotoxicity over 7 days and renal drug concentrations 24 h after the first dose were assessed. The effects of sodium maleate (400 mg/kg intraperitoneally) on megalin homeostasis were evaluated by determining the urinary megalin concentration and electron microscopic study of renal tissue. The serum/renal pharmacokinetics of polymyxin B were assessed in megalin-shedding rats. The onset of nephrotoxicity was correlated with the daily dose of polymyxin B. Renal polymyxin B concentrations were found to be 3.6 ± 0.4 µg/g, 9.9 ± 1.5 µg/g, and 21.7 ± 4.8 µg/g in the 5-mg/kg, 10-mg/kg, and 20-mg/kg dosing groups, respectively. In megalin-shedding rats, the serum pharmacokinetics of polymyxin B remained unchanged, but the renal exposure was attenuated by 40% compared to that of control rats. The onset of polymyxin B-induced nephrotoxicity is correlated with the renal drug exposure. In addition, megalin appears to play a pivotal role in the renal accumulation of polymyxin B, which might contribute to nephrotoxicity.

Significant publications on infectious diseases pharmacotherapy in 2015.

PURPOSE: The most important articles on infectious diseases (ID) pharmacotherapy published in the peer-reviewed literature in 2015, as nominated and selected by panels of pharmacists and others with ID expertise, are summarized. SUMMARY: Members of the Houston Infectious Diseases Network were asked to nominate articles published in prominent peer-reviewed journals in 2015 that were thought to have a major impact in the field of ID pharmacotherapy. A list of 55 nominated articles on general ID-related topics and 10 articles specifically related to human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) was compiled. In a national online survey, members of the Society of Infectious Diseases Pharmacists (SIDP) were asked to select from the list 10 general ID articles believed to have made a significant contribution to the field of ID pharmacotherapy and 1 article contributing to HIV/AIDS pharmacotherapy. Of the 361 SIDP members surveyed, 153 (42%) and 76 (21%) participated in the selection of general ID-related articles and HIV/AIDS-related articles, respectively. The 11 highest-ranked publications (10 general ID-related articles and 1 HIV/AIDS-related article) are summarized here. CONCLUSION: With the growing number of significant ID-related publications each year, it can be challenging to stay current with the literature. This review of important ID pharmacotherapy publications in 2015 may be helpful in identifying key articles and lessening this burden.

Dosing and Pharmacokinetics of Polymyxin B in Patients with Renal Insufficiency.

Polymyxin B remains the last-line treatment option for multidrug-resistant Gram-negative bacterial infections. Current U.S. Food and Drug Administration-approved prescribing information recommends that polymyxin B dosing should be adjusted according to the patient's renal function, despite studies that have shown poor correlation between creatinine and polymyxin B clearance. The objective of the present study was to determine whether steady-state polymyxin B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous polymyxin B (1.5 to 2.5 mg/kg [actual body weight] daily) were included. To measure polymyxin B concentrations, serial blood samples were obtained from each patient after receiving polymyxin B for at least 48 h. The primary outcome was polymyxin B exposure at steady state, as reflected by the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CLCR] ≥ 80 ml/min) at baseline, whereas 14 had renal insufficiency (CLCR < 80 ml/min). The mean AUC of polymyxin B ± the standard deviation in the normal renal function cohort was 63.5 ± 16.6 mg·h/liter compared to 56.0 ± 17.5 mg·h/liter in the renal insufficiency cohort (P = 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual body weight) did not result in a significant difference (28.6 ± 7.0 mg·h/liter versus 29.7 ± 11.2 mg·h/liter, P = 0.80). Polymyxin B exposures in patients with normal and impaired renal function after receiving standard dosing of polymyxin B were comparable. Polymyxin B dosing adjustment in patients with renal insufficiency should be reexamined.