Efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of pneumocystis pneumonia in human immunodeficiency virus-negative immunodeficient patients: A systematic review and meta-analysis

Abstract

Background Pneumocystis pneumonia (PCP) has a significant impact on the mortality of immunocompromised patients. It is not known whether the prophylactic application of trimethoprim-sulfamethoxazole (TMP-SMZ) can reduce the incidence of PCP and mortality in the human immunodeficiency virus (HIV)-negative immunodeficient population. The safety profile is also unknown. There have been few reports on this topic. The aim of this study was to systematically evaluate the efficacy and safety of the use of TMP-SMZ for the prevention of PCP in this population of patients from the perspective of evidence-based medicine. Methods A comprehensive search without restrictions on publication status or other parameters was conducted. Clinical randomized controlled trials (RCTs) or case-control trials (CCSs) of TMP-SMZ used for the prevention of PCP in HIV-negative immunocompromised populations were considered eligible. A meta-analysis was performed using the Mantel-Haenszel fixed-effects model or Mantel-Haenszel random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and reported. Results Of the 2392 records identified, 19 studies (n = 4135 patients) were included. The efficacy analysis results indicated that the PCP incidence was lower in the TMP-SMZ group than in the control group (OR = 0.27, 95% CI (0.10, 0.77), p = 0.01); however, the rate of drug discontinuation was higher in the TMP-SMZ group than in the control group (OR = 14.31, 95% CI (4.78, 42.91), p<0.00001). In addition, there was no statistically significant difference in the rate of mortality between the two groups (OR = 0.54, 95% CI (0.21, 1.37), p = 0.19). The safety analysis results showed that the rate of adverse events (AEs) was higher in the TMP-SMZ group than in the control group (OR = 1.92, 95% CI (1.06, 3.47), p = 0.03). Conclusions TMP-SMZ has a better effect than other drugs or the placebo with regard to preventing PCP in HIV-negative immunocompromised individuals, but it may not necessarily reduce the rate of mortality, the rate of drug discontinuation or AEs. Due to the limitations of the research methodologies used, additional large-scale clinical trials and well-designed research studies are needed to identify more effective therapies for the prevention of PCP.

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

“…1 The results of recent meta-analyses have shown that TMP-SMX is useful for preventing and treating Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients. 2,3 However, the daily dosage of TMP-SMX varies greatly depending on whether the drug is used for treatment or prophylaxis. Some patients take TMP-SMX orally at 80-400 mg/day, whereas others take 960-4800 mg/ day.…”

Trimethoprim-Sulfamethoxazole (Bactrim) Dose Optimization in Pneumocystis jirovecii Pneumonia (PCP) Management: A Systematic Review

“…The incidence of PCP was more than 50% in immunocompromised patients, 22–45% in patients with hematological malignancy, 5–15% in transplant recipients and around 2% in patients with rheumatoid diseases [ 3 , 4 ]. The clinical indications of PCP, such as tachycardia, hypoxia, tachypnea, shortness of breath, etc., are the major causes of death of immunosuppressive patients [ 5 ]. Therefore, PCP is considered a hallmark disorder indicating human immunodeficiency virus (HIV) infection [ 5 ].…”

“…The clinical indications of PCP, such as tachycardia, hypoxia, tachypnea, shortness of breath, etc., are the major causes of death of immunosuppressive patients [ 5 ]. Therefore, PCP is considered a hallmark disorder indicating human immunodeficiency virus (HIV) infection [ 5 ]. In the past few years, the occurrence or recurrence of PCP in HIV-positive patients has been reduced due to advanced technology and tools in diagnostic process, allowing early diagnosis; advanced management strategies in intensive care setting; and advanced preventive measures [ 6 ].…”

“…A retrospective study reported that the incidence of PCP and PCP-associated mortality was lower in patients with rheumatoid arthritis who received high-dose of glucocorticoids [ 8 ]. Another study reported that PCP developed in up to 40% of patients with the lymphoproliferative disease or acute lymphoblastic leukemia, and about 50% of patients experience hepatotoxicity [ 5 ]. Moreover, the incidence of adverse events (AEs) was decreased in non-HIV patients who received TMP-SMX prophylactically [ 9 , 10 ].…”

Effect of Prophylactic Dose of Trimethoprim-Sulfamethoxazole on Serum Creatinine in Japanese Patients With Connective Tissue Diseases

“…Prolonged treatment with high-dose steroids is a major risk factor for pneumocystis pneumonia (PCP) in patients with rheumatic diseases. 1 Patients with immune dysfunction induced by an inflammatory disease who receive more than 20 mg/d prednisolone for longer than 2 to 3 weeks should receive PCP prophylaxis. 2 - 5 Prophylactic trimethoprim-sulfamethoxazole (TMP/SMX) substantially decreases the incidence of PCP in patients with rheumatic diseases who receive prolonged, high-dose steroid treatment.…”