Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study)

doi:10.1136/bmj.39421.435949.BE

BMJ 2008;336:80-84 (12 January), doi:10.1136/bmj.39421.435949.BE (published 8 January 2008)

Research

Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study)

Rai Asghar, professor¹, Salem Banajeh, professor², Josefina Egas, microbiologist³, Patricia Hibberd, professor⁴, Imran Iqbal, professor⁵, Mary Katep-Bwalya, consultant⁶, Zafarullah Kundi, FRCP professor¹, Paul Law, associate professor⁷, William MacLeod, assistant professor⁸, Irene Maulen-Radovan, professor⁹, Greta Mino, professor¹⁰, Samir Saha, professor¹¹, Fernando Sempertegui, director³, Jonathon Simon, director⁸, Mathuram Santosham, professor⁷, Sunit Singhi, professor¹², Donald M Thea, professor⁸, Shamim Qazi, medical officer¹³, for the SPEAR (Severe Pneumonia Evaluation Antimicrobial Research) Study Group

¹ Rawalpindi General Hospital, Rawalpindi, Pakistan, ² Al-Sabeen Hospital, Sana’a, Yemen, ³ Corporacion Ecuatoriana de Biotecnologia, Quito, Ecuador, ⁴ Clinical Research Institute, New England Medical Center Tufts University, Boston, USA, ⁵ Nishter Hospital, Multan, Pakistan, ⁶ University Teaching Hospital, Lusaka, Zambia, ⁷ Department of International Health, Johns Hopkins Bloomberg University, Baltimore, USA, ⁸ Center for International Health and Development, Boston University School of Public Health, Boston, MA 02118, USA, ⁹ Instituto Nacional de Pediatria, Division de Investigacíon, Mexico City, Mexico, ¹⁰ Children’s Hospital, Guayaquil, Ecuador, ¹¹ Dhaka Shishu Hospital, Dhaka, Bangladesh, ¹² Post Graduate Institute of Medical Education and Research, Chandigarh, India, ¹³ Department of Child and Adolescent Health and Development, World Health Organization, Geneva, Switzerland

Correspondence to: D M Thea dthea{at}bu.edu

Objective To evaluate whether five days’ treatment withinjectable ampicillin plus gentamicin compared with chloramphenicolreduces treatment failure in children aged 2-59 months withcommunity acquired very severe pneumonia in low resource settings.

Design Open label randomised controlled trial.

Setting Inpatient wards within tertiary care hospitals in Bangladesh,Ecuador, India, Mexico, Pakistan, Yemen, and Zambia.

Participants Children aged 2-59 months with WHO defined verysevere pneumonia.

Intervention Chloramphenicol versus a combination of ampicillinplus gentamicin.

Main outcome measures Primary outcome measure was treatmentfailure at five days. Secondary outcomes were treatment failuredefined similarly among all participants evaluated at 48 hoursand at 10 and 21 days.

Results More children failed treatment with chloramphenicolat day 5 (16% v 11%; relative risk 1.43, 95% confidence interval1.03 to 1.97) and also by days 10 and 21. Overall, 112 bacterialisolates were obtained from blood and lung aspirates in 110children (11.5%), with the most common organisms being Staphylococcusaureus (n=47) and Streptococcus pneumoniae (n=22). In subgroupanalysis, bacteraemia with any organism increased the risk oftreatment failure at 21 days in the chloramphenicol group (2.09,1.41 to 3.10) but not in the ampicillin plus gentamicin group(1.12, 0.59 to 2.13). Similarly, isolation of S pneumoniae increasedthe risk of treatment failure at day 21 (4.06, 2.73 to 6.03)and death (5.80, 2.62 to 12.85) in the chloramphenicol groupbut not in the ampicillin plus gentamicin group. No differencewas found in treatment failure for children with S aureus bacteraemiain the two groups, but the power to detect a difference in thissubgroup analysis was low. Independent predictors of treatmentfailure by multivariate analysis were hypoxaemia (oxygen saturation<90%), receiving chloramphenicol, being female, and poorimmunisation status.

Conclusion Injectable ampicillin plus gentamicin is superiorto injectable chloramphenicol for the treatment of communityacquired very severe pneumonia in children aged 2-59 monthsin low resource settings.

Trial registration Current Controlled Trials ISRCTN39543942 [controlled-trials.com] .

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