Question 1: Co-trimoxazole dosing dilemma: what is the right dose?

While covering the paediatric haematology–oncology ward, you are asked to prescribe co-trimoxazole for prophylaxis against Pneumocystis jirovecii pneumonia (PJP). You refer to your usual drug resources discovering a variety of different dosing options and wonder which regimen you should prescribe. In immunocompromised children and adolescents without HIV infection (patient), which co-trimoxazole dosing regimen (intervention) is most effective in preventing PJP and best tolerated (outcome)? We searched Medline (1946 to current) and Embase (1974 to current) via the OVID interface in July 2015. The following keywords were used: trimethoprim (TMP)–sulfamethoxazole combination, TMP, sulfamethoxazole, drug combinations, pneumocystis infections, pneumocystis, pneumocystis pneumonia, chemoprevention, prophylaxis, chemoprophylaxis, prevention and control, infant, newborn, neonate, babies or baby, toddler, preschooler, child, adolescent, or paediatric. The search was limited to English language studies in humans aged 0–18 years. This identified a total of 972 publications. Articles were included if the specific dosing regimen of TMP–sulfamethoxazole was stated and outcomes were reported separately for patients under 18 years of age. Only studies examining PJP as an outcome were included. Studies of children with HIV infection and those without a robust case definition for PJP were excluded. Eleven articles fulfilled the inclusion criteria (table 1). The references of all articles were reviewed and no additional studies were identified. View this table: Table 1 Summary of evidence PJP is an opportunistic fungal infection that occurs in primary or acquired immunodeficiency syndromes. Prior to the widespread use of PJP prophylaxis, 15%–43% of children treated for haematological malignancies were affected.1 ,2 Combination TMP and sulfamethoxazole (co-trimoxazole) is effective in preventing PJP and is now the preferred prophylactic agent.3 ,4 However, there is significant variation in recommended dosing regimens. These range from doses on 1–3 consecutive or non-consecutive days per week, administered in 1–2 doses/day, calculated either by weight (usually 5 mg/kg/day TMP component) or body surface area …