Early use of corticosteroids in infants with a clinical diagnosis of Pneumocystis jiroveci pneumonia in Malawi: a double-blind, randomised clinical trial. (3rd April 2017)

• Record Type: Journal Article
• Authors: Newberry, Laura; O'Hare, Bernadette; Kennedy, Neil; Selman, Andrew; Omar, Sofia; Dawson, Pamela; Stevenson, Kim; Nishihara, Yo; Lissauer, Samantha; Molyneux, Elizabeth
• Is Part Of: Paediatrics and international child health. Volume 37:Number 2(2017)
• Page Start: 121
• Page End: 128
• Publication Date: 2017-04-03
• Subjects: HIV -- Pneumocystis jiroveci pneumonia -- infant; Pediatrics -- Developing countries -- Periodicals; Children -- Health and hygiene -- Developing countries -- Periodicals; Children -- Diseases -- Developing countries -- Periodicals; 618.920009172405
• DOI: 10.1080/20469047.2016.1260891
• Languages: English
• ISSNs: 2046-9047

Abstract

Abstract: Background : Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in infants with vertically acquired HIV infection and the most common cause of death in HIV-infected infants. Objectives : To determine whether early administration of adjuvant corticosteroids in addition to standard treatment reduces mortality in infants with vertically acquired HIV and clinically diagnosed PJP when co-infection with cytomegalovirus and other pathogens cannot be excluded. Methods : A double-blind placebo-controlled trial of adjuvant prednisolone treatment in HIV-exposed infants aged 2–6 months admitted to Queen Elizabeth Central Hospital, Blantyre who were diagnosed clinically with PJP was performed. All recruited infants were HIV-exposed, and the HIV status of the infant was confirmed by DNA-PCR. HIV-exposed and infected infants as well as HIV-exposed but non-infected infants were included in the study. The protocol provided for the addition of prednisolone to the treatment at 48 h if there was clinical deterioration or an independent indication for corticosteroid therapy in any patient not receiving it. Oral trimethoprim-sulfamethoxazole (TMP/SMX) therapy and full supportive treatment were provided according to established guidelines. Primary outcomes for all patients included survival to hospital discharge and 6-month post-discharge survival. Results : It was planned to enroll 200 patients but the trial was stopped early because of recruitment difficulties and a statistically significant result on interim analysis. Seventy-eight infants were enrolled between April 2012 and August 2014; 36 infants (46%) were randomised to receive corticosteroids plus standard treatment with TMP/SMX, and 42 infants (54%) received the standard treatment plus placebo. In an intention-to treat-analysis, the risk ratio of in-hospital mortality in the steroid group compared with the standard treatment plus placebo group was 0.53 [95% CI 0.29–0.97, p = 0.038]. The risk ratio of mortality at 6 months was 0.63 (95% CI 0.41–0.95, p = 0.029). Two children who received steroids developed bloody stools while in hospital. Conclusion : In infants with a clinical diagnosis of PJP, early use of steroids in addition to conventional TMP/SMX therapy significantly reduced mortality in hospital and 6 months after discharge.