Taking the challenge: A protocolized approach to optimize Pneumocystis pneumonia prophylaxis in renal transplant recipients

Abstract

While trimethoprim-sulfamethoxazole is considered first-line therapy for Pneumocystis pneumonia prevention in renal transplant recipients, reported adverse drug reactions may limit use and increase reliance on costly and less effective alternatives, often aerosolized pentamidine. We report our experience implementing a protocolized approach to trimethoprim-sulfamethoxazole adverse drug reaction assessment and rechallenge to optimize prophylaxis in this patient cohort. We retrospectively reviewed 119 patients receiving Pneumocystis pneumonia prophylaxis prior to and after protocol implementation. Forty-two patients (35%) had 48 trimethoprim-sulfamethoxazole adverse drug reactions documented either at baseline or during the prophylaxis period, of which 83% were non-immune-mediated and 17% were immune-mediated. Significantly more patients underwent trimethoprim-sulfamethoxazole rechallenge after protocol implementation (4/22 vs 23/27; P = .0001), with no recurrence of adverse drug reactions in 74%. In those who experienced a new or recurrent reaction (26%), all were mild and self-limiting with only 1 recurrence of an immune-mediated reaction. After protocol implementation, aerosolized pentamidine-associated costs were reduced. The introduction of a standard approach to trimethoprim-sulfamethoxazole rechallenge in the context of both prior immune and non-immune-mediated reactions was safe and successful in improving the uptake of first-line Pneumocystis pneumonia prophylaxis in renal transplant recipients.

Keywords: allergy; antibiotic prophylaxis; clinical research/practice; desensitization; drug toxicity; infectious disease; kidney transplantation/nephrology; kidney transplantation: living donor.

Figure 1. TMP-SMX ADR assessment and management protocol

PJP, Pneumocystis jirovecii pneumonia; TMP-SMX, trimethoprim-sulfamethoxazole; ADR, adverse drug reaction; G6PD, glucose-6-phosphate dehydrogenase; GI, gastrointestinal intolerance; SCAR, severe cutaneous adverse reaction; AP, aerosolized pentamidine ^a If TMP-SMX-associated rash within last two years, can consider dapsone rather than rechallenge ^b Drug fever, acute interstitial nephritis, immune complex deposition ^c Oral single dose challenge and observe for two hours (TMP-SMX 80mg-400mg). Patients reviewed 96 hours post-oral challenge to ensure no serious adverse event. Repeat follow-up as per treating physician. ^d Preferred prophylaxis strategy generally TMP-SMX 160mg-800mg daily or 3 times weekly. ^e For all patients proceed with TMP-SMX desensitization or alternatively, dapsone therapy may be employed. ^f Prescribe dapsone 100mg orally daily. Ensure G6PD deficiency screen negative prior to use. Dapsone monitoring includes full blood examination to check for anemia and/or hemolysis. Methemoglobulinemia can occur (normally symptomatic at >10%). Consider blood gas if symptomatic (e.g. central cyanosis, short of breath). May need to reduce dose to 50mg daily if toxicities occur. If ADR follows dapsone therapy then pentamidine usage should be considered. ^g For discussion on a case-by-case basis with treating unit. Avoid if TMP-SMX is the only implicated drug in cytopenia. ^h Avoid rechallenge if creatinine clearance < 40ml/min in a patient with previous renal impairment attributed to TMP-SMX. ⁱ Requires preauthorization from Infectious Diseases