Intravenous pentamidine for Pneumocystis carinii/jiroveci pneumonia prophylaxis in pediatric transplant patients

Abstract

SMX/TMP is the current gold standard for prophylaxis against PCP in immunocompromised pediatric patients. Currently, there are several second-line options for prophylaxis but many, including intravenous (IV) pentamidine, have not been reported to be as effective or as safe as SMX/TMP in the pediatric transplant population. This study is to determine the efficacy and safety of IV pentamidine in preventing PCP in pediatric transplant patients. A retrospective chart review was conducted to evaluate all transplant patients that received at least one dose of IV pentamidine from January 2010 to July 2013. The primary outcome, IV pentamidine efficacy, was evaluated by the incidence of PCP diagnosis for 28 days after the last dose of IV pentamidine if patient was transitioned to another agent for PCP prophylaxis. Patients on IV pentamidine for entire course of PCP prophylaxis were followed at least six months after discontinuation of IV pentamidine. The safety of IV pentamidine was assessed by the incidence of adverse events leading to pentamidine discontinuation. All data were analyzed using descriptive statistics. All transplant patients at CCHMC who had received IV pentamidine were reviewed, and 333 patients met inclusion criteria. The overall incidence of PCP was found to be 0.3% for pediatric transplant patients on pentamidine. Pentamidine was found to be safe, and the incidence of adverse events leading to discontinuation was 6% with the most common reason being tachycardia 2.1%. IV pentamidine is safe and effective as PCP prophylaxis in pediatric transplant patients with a PCP breakthrough rate of 0.3% (1 of 333 patients), and only 20 adverse events led to discontinuation. We recommend that IV pentamidine be considered as a second-line option in pediatric transplant patients who cannot tolerate SMX/TMP.

Pentamidine for Prophylaxis against Pneumocystis jirovecii Pneumonia in Pediatric Oncology Patients Receiving Immunosuppressive Chemotherapy

“…Two other studies reported no incidents of breakthrough PCP among pediatric oncology patients receiving aerosolized pentamidine for PCP prophylaxis (6, 7). The reported incidence of breakthrough PCP among pediatric oncology and solid organ transplant patients ranges from 0% to 1.3% overall (10,14,15,(17)(18)(19)(20). Our findings are comparable to breakthrough PCP incidence rates reported for TMP-SMX (5).…”

“…However, two of their reported cases had undergone HSCT, possibly contributing to the respiratory compromise. No patients in this study had pentamidine discontinued due to tachycardia, but pancreatitis was the reason for discontinuation in three patients (0.4%), which is similar to the rate reported by Clark et al (0.6%) (14). The rate of pancreatitis is notable; however, a sensitive definition was utilized to ensure we captured all potential cases of pancreatitis.…”

“…pentamidine appeared to be an acceptable agent for the prevention of PCP in HSCT recipients, including those Ͻ2 years of age. The reported discontinuation rates of pentamidine due to adverse drug events in previously published studies range from 0.7% to 6%; these events included anaphylaxis, tachycardia, nausea, and pancreatitis (7,14,15). Similarly, the present study found an overall rate of pentamidine discontinuation due to an adverse drug event of 3%.…”

“…Recent studies have reported acceptable breakthrough PCP rates (0% to 1.3%) with the use of i.v. pentamidine for PCP prophylaxis in immunocompromised children receiving chemotherapy or status post hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT) (10,14,15).…”

Organic cation transporter 1 (OCT1) is involved in pentamidine transport at the human and mouse blood-brain barrier (BBB)

“…It is also used to treat American cutaneous leishmaniasis and as a prophylactic for Pneumocystis jirovecii pneumonia [1]. HAT is a major public health problem in sub-Saharan Africa and is classified as one of the most neglected tropical diseases.…”