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Low-Dose TMP-SMX for Pneumocystis jirovecii Pneumonia Prophylaxis in Pediatric Solid Organ Transplant Recipients
Justin K Chen1, Jack Guerci1, Heather Corbo1
1Department of Pharmacy (JKC, JG, HC), NewYork-Presbyterian, New York, NY.
Insights
A low-dose trimethoprim-sulfamethoxazole (TMP-SMX) regimen effectively prevents Pneumocystis jirovecii pneumonia (PJP) in pediatric solid organ transplant recipients. This approach demonstrates an acceptable safety profile with manageable adverse effects.
Area of Science:
- Immunology
- Infectious Diseases
- Transplantation Medicine
Background:
- Pneumocystis jirovecii pneumonia (PJP) is a significant opportunistic infection in solid organ transplant (SOT) recipients.
- Standard trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis regimens can cause adverse drug effects.
- Optimizing PJP prophylaxis in pediatric SOT patients is crucial for patient outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of a low-dose TMP-SMX regimen for PJP prophylaxis in pediatric SOT recipients.
- To assess the incidence of breakthrough PJP infections.
- To determine the prevalence of TMP-SMX-associated adverse events.
Main Methods:
- Retrospective chart review of pediatric SOT patients (ages 0-21 years) from January 2012 to May 2020.
- Inclusion criteria: PJP prophylaxis with low-dose TMP-SMX for at least 6 months.
- Primary endpoint: breakthrough PJP infection; Secondary endpoints: adverse effects.
Main Results:
- No breakthrough PJP infections were diagnosed in the study cohort.
- 2.6% of patients were empirically treated for suspected PJP.
- Adverse events included hyperkalemia (2.6%), neutropenia (13.3%), thrombocytopenia (8.1%), creatinine elevations (15.9%), liver enzyme elevations (5.9%), and rash (1.5%).
Conclusions:
- Low-dose TMP-SMX is effective in preventing PJP in pediatric SOT recipients.
- The regimen exhibits an acceptable adverse effect profile.
- This strategy offers a viable alternative for PJP prophylaxis in this vulnerable population.
Objective:
Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that adversely affects solid organ transplant (SOT) recipients. Published guidelines endorse 5 to 10 mg/kg/day (trimethoprim component) trimethoprim-sulfamethoxazole (TMP-SMX) as the recommended regimen for PJP prevention, often resulting in drug-related adverse effects. We investigated the use of a low-dose TMP-SMX regimen given at 2.5 mg/kg/dose once daily every Monday, Wednesday, and Friday at a large pediatric transplantation center.
Methods:
A retrospective chart review was conducted, including patients ages 0 to 21 years who underwent SOT from January 1, 2012, to May 1, 2020, and who were subsequently started on PJP prophylaxis with low-dose TMP-SMX for a minimum of 6 months. The primary end point was the incidence of breakthrough PJP infection on the low-dose TMP-SMX regimen. Secondary end points include the prevalence of adverse effects characteristic of TMP-SMX.
Results:
A total of 234 patients were included in this study, and 6 of 234 patients (2.6%) were empirically transitioned to treatment dosing of TMP-SMX given a clinical concern for PJP, although none received a diagnosis of PJP. There were 7 patients (2.6%) who experienced hyperkalemia, 36 (13.3%) had neutropenia, and 22 (8.1%) had thrombocytopenia (all grade 4). Clinically significant serum creatinine elevations were seen in 43 of 271 patients (15.9%). Elevations of liver enzymes were seen in 16 of 271 patients (5.9%). Rash was documented in 4 of 271 patients (1.5%).
Conclusions:
In our patient cohort, low-dose TMP-SMX preserves the efficacy of PJP prophylaxis while providing an acceptable adverse effect profile.
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