Maitland, K

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This site uses cookies. More info Close By continuing to browse the site you are agreeing to ouruse of cookies. Find out more here CloseEditorialsAntimicrobials in children admitted to hospitalin malaria endemic areasBMJ 2010; 340 doi: http://dx.doi.org/10.1136/bmj.c1818 (Published 08 April 2010) Cite this as: BMJ2010;340:c1818Kathryn Maitland, professor in tropical paediatric infectious diseasesDepartment of Paediatrics, Division of Medicine, Imperial College, London W2 1PGkathryn.maitland@gmail.comIdentifying children with sepsis is the first major challengeThe cornerstones of the Surviving Sepsis Campaign are the prompt identification of sepsis and thesubsequent implementation of evidence based treatments.1 A key component of this strategy is thetimely use of antibiotics. Even in countries embracing these guidelines, “sepsis” is largely diagnosedclinically, so prompt recognition and treatment should be possible even for hospitals with basicclinical and diagnostic capabilities. What are the barriers to the implementation of this goal and, morespecifically, to the targeted antimicrobial treatment of children admitted to hospital in malariaendemic Africa? In the linked prospective study (doi:10.1136/bmj.c1350), Nadjm and colleaguesassess the performance of the World Health Organization’s referral care manual (which guides theuse of antibiotics in children admitted to hospital in Africa) in identifying children with invasivebacterial disease in an area of intense malaria transmission.2Four major challenges exist. Firstly, presentation to hospital with febrile disease is extremelycommon, so making informed choices about who to treat with parenteral antibiotics needs to bebalanced against overtreatment. Secondly, in malaria endemic areas, children often carry falciparummalaria asymptomatically, so malaria is overdiagnosed at the expense of other infectious conditions.Evidence also suggests that accurate microscopy has limited influence on prescribing practice.3Thirdly, complex, patient specific prescribing is not encouraged. The limited pharmacopoeia, drivenlargely by cost, is poorly informed by clinical audit. Good epidemiological evidence is hard to findbecause routine microbiological investigation is scarce and reports are limited to a few researchcentres.4 Finally, the term sepsis, which broadly implies a sepsis-like syndrome,5 is not evenmentioned in referral care practice guidelines.6 Instead, probably for historical programmaticreasons, treatment strategies are largely limited to one syndrome, so treatment of suspectedbacterial infection is covered separately in other management guidelines. Practically, this presents1Antimicrobials in children admitted to hospital in malaria en... http://www.bmj.com/content/340/bmj.c1818.full.print?1 of 4 18/09/2015 11:55challenges for bedside management because many children present with clinical features of multiplesyndromes.7Nadjm and colleagues describe a prospective microbiological study of 3639 febrile children, medianage 1.6 years, presenting to a rural hospital in a highly malarious area of Tanzania, whereimmunisation for Haemophilus influenzae or Streptococcus pneumoniae is not routine.2 Childrenwere systematically screened for malaria and invasive bacterial disease by culture of blood andcerebrospinal fluid (where indicated). The unique component of this study was assessment of theperformance of the WHO first level care guidelines to identify children with invasive bacterial diseaseby applying the case definitions retrospectively and with respect to malaria status. Overall, 341 (9%)cases had invasive bacterial disease, of which 58 (17%) episodes were fatal. One hundred and fortytwo children had HIV infection. Current or recent falciparum infection occurred in 2195 (60%)admissions; 100 (4.5%) of these children had invasive bacterial disease. Mortality was higher inchildren with invasive bacterial disease (17% v 4%), irrespective of malaria status. Importantly,clinical diagnosis alone, using WHO classification, failed to identify 30% of all invasive bacterialdisease and 17% of fatal invasive bacterial disease cases. The sensitivity of the guidelines to detectinvasive bacterial disease were 60% and 70% in malaria and non-malaria cases, respectively.Improvements in the specificity to 86% could be gained by addition of HIV status (now routine inpaediatric admissions), severe anaemia (haemoglobin <50 g/l, prostration (decreasedconsciousness), and high fever, but at the expense of poor specificity (22-29%). Only 47% oforganisms were susceptible to the antibiotics recommended for the clinical diagnosis. The guidelinewas best at detecting meningo-encephalopathy when the organisms were predominantly Grampositive (96% were sensitive to the ampicillin-gentamicin combination). The guideline performancewas poorest in children with malaria, where 75% of invasive bacterial disease was with Gramnegative bacteria; both non-typhoidal salmonellae and other Gram negative bacteria were common.Non-typhi salmonella more commonly complicated cases of recent malaria or those with densities ofless than 5000 parasites/µl, whereas other Gram negative bacteria were the predominant organismsin cases with higher densities.This study adds to the growing literature on the epidemiology of invasive bacterial disease in malariaendemic areas, and it shows that non-typhoidal salmonellae contribute substantially to the spectrumof infection.8 9 10 Even for those presenting with one of the three hierarchical definitions of“pneumonia” severity, non-typhoidal salmonella was still the predominant pathogen, and treatmentwould have been either with oral antibiotics or parenteral penicillin. Another limitation of “syndromic”management is seen in children with a respiratory-type presentation, who are routinely classified ashaving pneumonia and managed as such. Although the case definition for severe malariaincorporates respiratory distress (a manifestation of metabolic acidosis), which is a commoncomplication and the best independent predictor of fatal outcome,11 the disease may bemisclassified as pneumonia.12 For severe malaria no specific recommendations for antibiotics aremade in the hospital management guideline.This study highlights the inadequacy of the time honoured antibiotics that are in routine use acrossAfrica, and that are likely to remain unchanged even after immunisation for H influenzae and Spneumoniae is introduced into malaria endemic Africa. Notwithstanding arguments for rationalantibiotic prescribing practices, Nadjm and colleagues’ study highlights the need to consider thirdAntimicrobials in children admitted to hospital in malaria en... http://www.bmj.com/content/340/bmj.c1818.full.print?2 of 4 18/09/2015 11:55generation cephalosporins or quinolones for future trials and treatment guidelines. Nevertheless,correct identification of children with sepsis in resource poor settings continues to be a majorpractical, clinical, and therapeutic challenge.NotesCite this as: BMJ 2010;340:c1818FootnotesResearch, doi:10.1136/bmj.c1350Competing interests: The author has completed the Unified Competing Interest form atwww.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) anddeclares: (1) No financial support for the submitted work from anyone other than her employer;(2) No financial relationships with commercial entities that might have an interest in thesubmitted work; (3) No spouse, partner, or children with relationships with commercial entitiesthat might have an interest in the submitted work; (4) No non-financial interests that may berelevant to the submitted work.Provenance and peer review: Commissioned; not externally peer reviewed.ReferencesDellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaignguidelines for management of severe sepsis and septic shock. Crit Care Med2004;32:858-73.1. Nadjm B, Amos B, Mtove G, Ostermann J, Chonya S, Wangai H, et al. WHO guidelines for antimicrobialtreatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission:prospective study. BMJ2010;340:c1350.2. Reyburn H, Mbatia R, Drakeley C, Carneiro I, Mwakasungula E, Mwerinde O, et al. Overdiagnosis ofmalaria in patients with severe febrile illness in Tanzania: a prospective study. BMJ2004;329:1212.3. Berkley JA, Maitland K, Mwangi I, Ngetsa C, Mwarumba S, Lowe BS, et al. Use of clinical syndromes totarget antibiotic prescribing in seriously ill children in malaria endemic area: observational study. BMJ2005;330:995.4. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions forsepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med2005;6:2-8.5. WHO. Hospital care for children: guidelines for the management of common illnesses with limitedresources. 2005. www.who.int/child-adolescent-health/publications/CHILD_HEALTH/PB.htm.6. Berkley JA, Bejon P, Mwangi T, Gwer S, Maitland K, Williams TN, et al. HIV infection, malnutrition, andinvasive bacterial infection among children with severe malaria. Clin Infect Dis2009;49:336-43.7. Walsh AL, Phiri AJ, Graham SM, Molyneux EM, Molyneux ME. Bacteremia in febrile Malawian children:clinical and microbiologic features. Pediatr Infect Dis J2000;19:312-8.8. Bahwere P, Levy J, Hennart P, Donnen P, Lomoyo W, Dramaix-Wilmet M, et al. Community-acquiredbacteremia among hospitalized children in rural central Africa. Int J Infect Dis2001;5:180-8.9. Antimicrobials in children admitted to hospital in malaria en... http://www.bmj.com/content/340/bmj.c1818.full.print?3 of 4 18/09/2015 11:55Berkley JA, Lowe BS, Mwangi I, Williams TN, Bauni E, Mwarumba S, et al. Bacteremia amongst childrenadmitted to a rural hospital in Kenya. N Engl J Med2005;352:39-47.10. Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, et al. Indicators of life-threatening malariain African children. N Engl J Med1995;332:1399-404.11. English M, Punt J, Mwangi I, McHugh K, Marsh K. Clinical overlap between malaria and severe pneumoniain Africa children in hospital. Trans R Soc Trop Med Hyg1996;90:658-62.12. Antimicrobials in children admitted to hospital in malaria en... http://www.bmj.com/content/340/bmj.c1818.full.print?4 of 4 18/09/2015 11:55

Antimicrobials in children admitted to hospital in malaria endemic areas

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Antimicrobials in children admitted to hospital in malaria endemic areas

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