|A systematic review of two different trimetoprim-sulfamethoxazole regimens used to prevent Pneumocystis jirovecii and no prophylaxis at all in transplant recipients: appraising the evidence
|Di Cocco P, Orlando G, Bonanni L, D'Angelo M, Clemente K, Greco S, Gravante G, Madeddu F, Scelzo C, Famulari A, Pisani F
The review concluded that low-dose trimethoprim/sulphamethoxazole gave similar results to the high-dose regime and should be considered a safe option in transplanted patients. The review suffered from potential sources of bias that included a limited search, inclusion of poor quality studies, heterogeneity and a small number of studies. The authors' conclusions are unlikely to be reliable.
To compare the effectiveness of low-dose and full-dose regimens of trimethoprim/sulphamethoxazole (TMP-SMX) with no antibiotic in the prevention of pneumocystis jirovecii pneumonia (PJP) in transplant recipients.
MEDLINE, EMBASE and The Cochrane library were searched. Search dates were not reported. Search terms were reported. The search was restricted to studies written in English.
Prospective, randomised studies or retrospective case-control studies that compared TMP-SMX in full dose (160/800mg daily) or low dose (80/400mg daily or 160/800mg every other day) with no treatment (no antibiotic prophylaxis) in any transplant recipients were considered. The outcome of interest was occurrence of PJP in each treatment group. Side effects were reported.
Most of the transplant recipients were male. Average age ranged from 41 to 52 years (where reported). The organs transplanted were heart, heart-lung, kidney-pancreas and liver. Timing of initiating prophylactic treatment post transplant varied and ranged between zero and 80 months. Concurrent immunosuppressants included cyclosporin, azathioprine and low-dose steroids.
The authors did not report how many people performed the study selection
Assessment of study quality
Study quality was assessed using the GRADE system to investigate consistency, directness, quality and study design. Each study was assigned a grade for overall quality (very low, low, moderate, high).
The authors did not state how many people performed the quality assessment.
Data were extracted to calculate proportions of patients who experienced PJP in each treatment arm.
The authors did not state how many people performed the data extraction.
Methods of synthesis
The proportion of cases of PJP in each treatment arm was obtained and combined across all studies. Three pair-wise comparisons were made using Fisher's exact test (P<0.05) that compared full dose versus no prophylaxis, low dose versus no prophylaxis and full dose versus low dose.
Results of the review
Four studies (n=576, range 56 to 375 patients) were included in the review: two retrospective case-control studies (n=450), one prospective randomised trial (n=56) and one prospective observational study (n=70). Quality assessment ranked three studies to be of very low quality and one as having low quality.
Pair-wise comparisons (proportion of PJP occurrence): Full-dose TMP-SMX was superior to no treatment in preventing PJP occurrence: 0% (zero out of 181) versus 11% (31 out of 290), Fisher's exact test (P<0.001). Low-dose treatment was superior to no prophylaxis: 1%(one out of 105) versus 11% (31 out of 290), Fisher's exact test (P<0.001). There were no significant differences between the full-dose and low-dose treatments.
Side effects: Changes in serum creatinine at the start of treatment were reported in one low-dose study and one high-dose study. There were no reports of leukopenia in any of the studies. Gastrointestinal side effects were noted in two of the studies.
The authors concluded that low-dose TMP-SMX gave similar results as the full-dose regimen in the prevention of PJP and seemed a feasible and safe option for transplanted patients.
The review addressed a clear question with respect to study design, participants, interventions and outcomes. Relevant databases were searched, but search dates were not reported. The search was restricted to published studies written in English, which meant that some important studies may have been missed and the risk of publication bias could not be excluded. Study quality was formally assessed and indicated the presence of studies with very poor quality, which increased the risk of bias. It was unclear how many people performed the review process. Statistical heterogeneity was not assessed, although the authors acknowledged the limitations (such as variability among transplanted organs) of including studies with great variability. Use of standard statistical methods may have been limited by the inclusion of a small number of studies comprised of small sample sizes.
This review suffered from potential sources of bias that included a limited search, inclusion of studies with poor quality, heterogeneity among studies and a small number of studies comprised of small sample sizes. The authors' conclusions are unlikely to be reliable and should be treated with caution.
Implications of the review for practice and research
Practice: The authors stated that a low-dose regimen that used half the dose of TMP-SMX was feasible and safe for transplanted patients
Research: The authors did not state any implications for research.
Di Cocco P, Orlando G, Bonanni L, D'Angelo M, Clemente K, Greco S, Gravante G, Madeddu F, Scelzo C, Famulari A, Pisani F. A systematic review of two different trimetoprim-sulfamethoxazole regimens used to prevent Pneumocystis jirovecii and no prophylaxis at all in transplant recipients: appraising the evidence. Transplantation Proceedings 2009; 41(4): 1201-1203
Subject indexing assigned by NLM
Anti-Infective Agents /administration & Humans; Pneumocystis jirovecii; Pneumonia, Pneumocystis /drug therapy; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination /administration & dosage; dosage /therapeutic use
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.