Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim therapy for Pneumocystis jirovecii pneumonia in patients with systemic rheumatic diseases: A retrospective multicenter study

J Infect Chemother. 2019 Apr;25(4):253-261. doi: 10.1016/j.jiac.2018.11.014. Epub 2019 Jan 12.

Abstract

Objectives: To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases.

Methods: In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10-15 mg/kg/day; and the high and conventional, 15-20 mg/kg/day for TMP dose.

Results: Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs.

Conclusions: Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases.

Keywords: Adverse drug reactions; Pneumocystis pneumonia; Sulfamethoxazole; Systemic rheumatic diseases; Trimethoprim.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Immunosuppression Therapy / methods
  • Male
  • Middle Aged
  • Opportunistic Infections / complications
  • Opportunistic Infections / drug therapy*
  • Opportunistic Infections / immunology
  • Opportunistic Infections / mortality
  • Pneumocystis carinii / isolation & purification
  • Pneumonia, Pneumocystis / complications
  • Pneumonia, Pneumocystis / drug therapy*
  • Pneumonia, Pneumocystis / immunology
  • Pneumonia, Pneumocystis / mortality
  • Retrospective Studies
  • Rheumatic Diseases / complications*
  • Rheumatic Diseases / drug therapy
  • Rheumatic Diseases / immunology
  • Rheumatic Diseases / mortality
  • Survival Rate
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage*
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects

Substances

  • Anti-Bacterial Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination