Complications and outcomes of trimethoprim–sulphamethoxazole as chemoprophylaxis for pneumocystis pneumonia in renal transplant recipients

Mitsides, Nicos; Greenan, Kerry; Green, Darren; Middleton, Rachel; Lamerton, Elizabeth; Allen, Judith E.; Redshaw, J; Chadwick, Paul; Subudhi, Chinari; Wood, Grahame

doi:10.1111/nep.12201

Cited by 35 publications

(37 citation statements)

References 28 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As often seen in clinical practice, Type-A ADRs contributed to a significant number of antibiotic allergy labels (10). Mitsides et al (11) reported similar rates of TMP-SMX ADR and discontinuation (38%) in 290 RTRs receiving PJP prophylaxis, predominantly due to SeCr rise. This rise is likely due to inhibition of tubular Cr secretion by trimethoprim which can result in reversible increases in SeCr higher than 35% in patients with pre-existing renal impairment (11) and, therefore, likely to recur on TMP-SMX rechallenge.…”

Section: Discussionmentioning

confidence: 91%

“…The majority of patients were male (66%), having undergone their first transplant (91%), with a median ageadjusted Charlson comorbidity score of 4 (interquartile range [IQR]: 3, 6) ( Table 1). IgA nephropathy 23 (19) Polycystic kidney disease 13 (11) Reflux nephropathy 11 (9) Focal segmental glomerulosclerosis 10 (9) Glomerulonephritis (unspecified) 8 (7) Unknown cause 4 (3)…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

Urbancic

Ierino

Phillips

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

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

Urbancic

Ierino

Phillips

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Hence, we suggest a 6–12 month course of prophylaxis following either an episode of acute graft rejection or CMV infection. Although some complications have been reported with the use of TMP/SMX for PJP prophylaxis, major complications are relatively rare 28 ; therefore, the benefits of PJP prophylaxis outweigh the risks.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for Pneumocystis jirovecii pneumonia (PJP) in kidney transplantation recipients

Lee

Huh

Joo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised patients. The aim of this study was to evaluate risk factors for PJP in kidney transplantation recipients. We conducted a retrospective analysis of patient data from 500 consecutive kidney transplants performed at Severance Hospital between April 2011 and April 2014. Eighteen kidney transplantation recipients (3.6%) were diagnosed with PJP. In the univariate analysis, acute graft rejection, CMV infection, use of medication for diabetes mellitus, and lowest lymphocyte count were associated with PJP. Recipients who experienced acute graft rejection (odds ratio [OR] 11.81, 95% confidence interval [CI] 3.06–45.57, P < 0.001) or developed CMV infection (OR 5.42, 95% CI 1.69–17.39, P = 0.005) had high odds of PJP in multivariate analysis. In the acute graft rejection subgroup, patients treated with anti-thymocyte globulin (ATG) had significantly higher odds of PJP (OR 5.25, 95% CI 1.01–27.36, P = 0.006) than those who were not. Our data suggest that acute graft rejection and CMV infection may be risk factors for PJP in kidney transplant patients. The use of ATG for acute graft rejection may increase the risk of PJP.

show abstract

“…The avoidance of TMP‐SMX for reasons of myelosuppression also appears unfounded, as rates of leukopenia in solid organ transplant cohorts when TMP‐SMX is employed as prophylaxis have been reported at less than 2% . Modern studies have suggested that TMP‐SMX therapy when employed as prophylaxis in hematological malignancy does not impact on the degree or duration of neutropenia .…”

Section: Discussionmentioning

confidence: 99%

“…13 We observed suboptimal G6PD screening in our dapsone patient cohort, with less than half under- The avoidance of TMP-SMX for reasons of myelosuppression also appears unfounded, as rates of leukopenia in solid organ transplant cohorts when TMP-SMX is employed as prophylaxis have been reported at less than 2%. 16,17 Modern studies have suggested that TMP-SMX therapy when employed as prophylaxis in hematological malignancy does not impact on the degree or duration of neutropenia. 18 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.…”

Section: Discussionmentioning

confidence: 99%

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

Urbancic

Pisasale

Wight

et al. 2018

Transplant Infectious Dis

View full text Add to dashboard Cite

Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.

show abstract

Complications and outcomes of trimethoprim–sulphamethoxazole as chemoprophylaxis for pneumocystis pneumonia in renal transplant recipients

Abstract: Use of chemoprophylaxis is an effective strategy in dealing with a PCP outbreak but can lead to a high number of complications. Rises in serum Cr can cause significant concern and increase in the number of investigations.

Cited by 35 publications

References 28 publications

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

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

Risk factors for Pneumocystis jirovecii pneumonia (PJP) in kidney transplantation recipients

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

Contact Info

Product

Resources

About