Evaluation of effectiveness, hyperkalaemia, and hepatotoxicity of trimethoprim-sulphamethoxazole prophylaxis for Pneumocystis jirovecii pneumonia in paediatric patients: A single-centre retrospective study

Int J Antimicrob Agents. 2024 May;63(5):107151. doi: 10.1016/j.ijantimicag.2024.107151. Epub 2024 Mar 19.

Abstract

Background: American guidelines recommend trimethoprim-sulphamethoxazole (TMP-SMX) for preventing Pneumocystis jirovecii pneumonia (PJP) in paediatric patients at doses of 5-10 mg/kg/d of the TMP component, administered either daily, three times weekly, or twice weekly. However, limited studies describe the effectiveness and safety of these prophylactic regimens. Our study aimed to assess the clinical effectiveness and incidence of adverse events associated with each TMP-SMX regimen in paediatric patients, and to identify risk factors for adverse events.

Methods: We collected data regarding the onset of PJP, hyperkalaemia, and hepatotoxicity in patients aged 0-18 years who underwent prophylaxis with TMP-SMX from July 2018 to June 2023.

Results: A total of 215 paediatric patients met the inclusion criteria. No patients developed PJP. Hyperkalaemia occurred in 14.7%, patients receiving TMP-SMX daily, 15.4% receiving it three times weekly, and 15.5% receiving it twice weekly. Hepatotoxicity was most frequent in patients receiving TMP-SMX twice weekly (19%), followed by those receiving it three times weekly (7.7%), and daily (5.9%). Younger patients were significantly more prone to developing hyperkalaemia or hepatotoxicity. Patients aged <1 year had the highest incidences of hyperkalaemia (56.5%), and those aged 1-2 years had the highest incidence of hepatotoxicity (25%).

Conclusions: No patient developed PJP under various dosage prophylactic regimens of TMP-SMX. However, our findings suggest the need to monitor potassium levels and hepatic function in patients undergoing any of the three TMP-SMX regimens. In particular, patients aged <1 year old and 1-2 years old face a higher risk of hyperkalaemia and hepatotoxicity, respectively.

Keywords: Dosage regimen; Paediatric patient; Trimethoprim-sulphamethoxazole.

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotic Prophylaxis
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / prevention & control
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Hyperkalemia* / prevention & control
  • Infant
  • Infant, Newborn
  • Male
  • Pneumocystis carinii*
  • Pneumonia, Pneumocystis* / drug therapy
  • Pneumonia, Pneumocystis* / prevention & control
  • Retrospective Studies
  • Trimethoprim, Sulfamethoxazole Drug Combination* / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination* / adverse effects
  • Trimethoprim, Sulfamethoxazole Drug Combination* / therapeutic use

Substances

  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Anti-Bacterial Agents