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=0.0001), 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.

Sulfonamide desensitization in solid organ transplant recipients: A protocol‐driven approach during the index transplant hospitalization

“…Urbancic et al reported on a TMP‐SMX re‐challenge protocol in kidney transplant recipients; nearly three quarters (74% of 27 patients) tolerated protocol‐driven re‐challenge without allergic or adverse drug reaction resulting in discontinuation, supporting previous literature that an initial non‐severe, non‐anaphylactic sulfonamide reaction does not preclude subsequent tolerance . McLaughlin et al reported on switch to atovaquone and subsequent successful re‐initiation of TMP‐SMX in 100% (n = 14) of kidney transplant recipients who were re‐challenged; in this retrospective review, however, all but one of the 14 patients who were re‐challenged with TMP‐SMX had been switched to atovaquone for reasons other than hypersensitivity (eg, neutropenia, hyperkalemia, renal insufficiency).…”

Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients

“…19 Therefore, for those with mild delayed TMP-SMX allergy, TMP-SMX rechallenge or desensitization should be considered in the peritransplant period or at commencement of induction chemotherapy, as an alternative to dapsone in accordance with previously published protocols. 9 This study highlights that although dapsone is an alternative agent in PJP prophylaxis, it requires careful monitoring of oxidative…”

“…A recent Cochrane review of PJP prophylaxis in the non‐HIV setting found no difference in adverse events requiring discontinuation when comparing TMP‐SMX to no treatment or placebo . Therefore, for those with mild delayed TMP‐SMX allergy, TMP‐SMX rechallenge or desensitization should be considered in the peritransplant period or at commencement of induction chemotherapy, as an alternative to dapsone in accordance with previously published protocols …”

“…Common TMP‐SMX ADRs were categorized as either Type‐A (nonimmune‐mediated) or Type‐B (immune‐mediated) according to standard definitions . Following accurate TMP‐SMX ADR phenotyping, patients could undergo either TMP‐SMX rechallenge, desensitization or continued avoidance as per our previously published protocol, developed in consultation with an external expert who leads an international antibiotic allergy service . Patients with a history of mild delayed TMP‐SMX hypersensitivity (Type‐B), real/perceived myelosuppression risk, or other Type‐A TMP‐SMX ADR could undergo rechallenge with a single oral dose (TMP‐SMX; 160 mg‐800 mg OR 80 mg‐400 mg) .…”

Multicomponent Reactions Upon the Known Drug Trimethoprim as a Source of Novel Antimicrobial Agents

“…TMP is usually used in combinationwith Sulfamethoxazole (SMX) to treat lower urinary tract infections and acute invasive diarrhea/bacterial dysentery as first and second choice, respectively (WHO, 2017), respiratory infections in cystic fibrosis patients caused by Staphylococcus aureus , among other many infections. Lately, it has also been used for preventing infections from the opportunistic pathogen Pneumocystis carinii (Urbancic et al, 2018), which normally causes pneumonia in patients with AIDS. Both drugs act on the folic acid biosynthetic route by inhibiting two enzymes: dihydrofolate reductase (DHFR) and dihydropteroate synthetase, respectively.…”