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Comparative effectiveness of injectable penicillin versus a combination of penicillin and gentamicin in children with pneumonia characterised by indrawing in Kenya: a retrospective observational study
  1. Lucas Malla1,
  2. Rafael Perera-Salazar2,
  3. Emily McFadden2,
  4. Mike English1,3
  1. 1 Nuffield Department of Medicine, University of Oxford, Oxford, UK
  2. 2 Nuffield Department of Primary Health Care Sciences, University of Oxford, Oxford, UK
  3. 3 Health Services Unit, Kenya Medical Research Institute-Wellcome Trust Research Programme, Nairobi, Kenya
  1. Correspondence to Lucas Malla; lmalla{at}kemri-wellcome.org

Abstract

Objectives Kenyan guidelines for antibiotic treatment of pneumonia recommended treatment of pneumonia characterised by indrawing with injectable penicillin alone in inpatient settings until early 2016. At this point, they were revised becoming consistent with WHO guidance after results of a Kenyan trial provided further evidence of equivalence of oral amoxicillin and injectable penicillin. This change also made possible use of oral amoxicillin for outpatient treatment in this patient group. However, given non-trivial mortality in Kenyan children with indrawing pneumonia, it remained possible they would benefit from a broader spectrum antibiotic regimen. Therefore, we compared the effectiveness of injectable penicillin monotherapy with a regimen combining penicillin with gentamicin.

Setting We used a large routine observational dataset that captures data on all admissions to 13 Kenyan county hospitals.

Participants and measures The analyses included children aged 2–59 months. Selection of study population was based on inclusion criteria typical of a prospective trial, primary analysis (experiment 1, n=4002), but we also explored more pragmatic inclusion criteria (experiment 2, n=6420) as part of a secondary analysis. To overcome the challenges associated with the non-random allocation of treatments and missing data, we used propensity score (PS) methods and multiple imputation to minimise bias. Further, we estimated mortality risk ratios using log binomial regression and conducted sensitivity analyses using an instrumental variable and PS trimming.

Results The estimated risk of dying, in experiment 1, in those receiving penicillin plus gentamicin was 1.46 (0.85 to 2.43) compared with the penicillin monotherapy group. In experiment 2, the estimated risk was 1.04(0.76 to 1.40).

Conclusion There is no statistical difference in the treatment of indrawing pneumonia with either penicillin or penicillin plus gentamicin. By extension, it is unlikely that treatment with penicillin plus gentamicin would offer an advantage to treatment with oral amoxicillin.

  • pneumonia
  • missing data
  • propensity scores
  • comparative effectiveness

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors LM did an initial draft of this manuscript with the support of RP-S, EM and ME. Thereafter, all authors edited subsequent versions and approved the final copy.

  • Funding The authors are grateful for the funds from the Wellcome Trust (#097170) that support ME through a fellowship and additional funds from a Wellcome Trust core grant awarded to the KEMRI-Wellcome Trust Research Programme (#092654) that supported this work. LM is supported by a Nuffield Department of Medicine Prize DPhil Studentship and Clarendon Scholarship (Oxford University).

  • Disclaimer The funders had no role in drafting or submitting this manuscript.

  • Competing interests None declared.

  • Ethics approval This analysis is based on a larger project (CIN) which was cleared by the Kenya Medical Research Institute Ethics and Review Board (Protocol number: 2465).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The hospital-specific datasets are in custody of the hospitals participating in CIN (these datasets have been deidentified).

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