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Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.

ABSTRACT: Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa.We prospectively followed a cohort of children (2-59 months), diagnosed by community health workers with fast-breathing pneumonia using World Health Organisation (WHO) integrated community case management guidelines. Cases were followed at days 5 and 14 by study data collectors, who assessed a range of pre-determined clinical features for treatment outcome. We built the prognostic model using eight pre-defined parameters, using multivariable logistic regression, validated through bootstrapping.We assessed 1,542 cases of which 769 were included (32% ineligible; 19% defaulted). The treatment failure rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis (OR: 1.62; 95% CI: 1.06, 2.47) and moderate malnutrition (OR: 1.88; 95% CI: 1.09, 3.26) were associated with treatment failure. The model demonstrated poor calibration and discrimination (c-statistic: 0.56).This study suggests that it may be difficult to create a pragmatic community-level prognostic child pneumonia tool based solely on clinical markers and pulse oximetry in an HIV and malaria endemic setting. Further work is needed to identify more accurate and reliable referral algorithms that remain feasible for use by community health workers.

SUBMITTER: King C

PROVIDER: S-EPMC4551481 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.

King Carina C McCollum Eric D ED Mankhambo Limangeni L Colbourn Tim T Beard James J Hay Burgess Debbie C DC Costello Anthony A Izadnegahdar Rasa R Lufesi Norman N Masache Gibson G Mwansambo Charles C Nambiar Bejoy B Johnson Eric E Platt Robert R Mukanga David D

PloS one 20150827 8

<h4>Background</h4>Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa.<h4>Method</h ...[more]

PMID: 26313752

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Project description:BackgroundDue to increasing antimicrobial resistance in low-resource settings, strategies to rationalize antibiotic treatment of children unlikely to have a bacterial infection are needed. This study's objective was to utilize a database of placebo treated Malawian children with World Health Organization (WHO) fast breathing pneumonia to develop a prognostic risk score that could aid antibiotic decision making.MethodsWe conducted a secondary analysis of children randomized to the placebo group of the Innovative Treatments in Pneumonia (ITIP) fast breathing randomized, controlled, noninferiority trial. Participants were low-risk HIV-uninfected children 2-59 months old with WHO fast breathing pneumonia in Lilongwe, Malawi. Study endpoints were treatment failure, defined as either disease progression at any time on or before Day 4 of treatment or disease persistence on Day 4, or relapse, considered as the recurrence of pneumonia or severe disease among previously cured children between Days 5 and 14. We utilized multivariable linear regression and stepwise model selection to develop a model to predict the probability of treatment failure or relapse.ResultsTreatment failure or relapse occurred in 11.5% (61/526) of children included in this analysis. The final model incorporated the following predictors: heart rate terms, mid-upper arm circumference, malaria status, water source, family income, and whether or not a sibling or other child in the household received childcare outside the home. The model's area under the receiver operating characteristic score was 0.712 (95% confidence interval 0.66, 0.78) and it explained 6.1% of the variability in predicting treatment failure or relapse (R2, 0.061). For the model to categorize all children with treatment failure or relapse correctly, 77% of children without treatment failure or relapse would require antibiotics.ConclusionThe model had inadequate discrimination to be appropriate for clinical application. Different strategies will likely be required for models to perform accurately among similar pediatric populations.

Project description:BackgroundPneumonia is a leading cause of mortality in children <5 years globally. Early identification of hospitalized children with pneumonia who may fail antibiotics could improve outcomes. We conducted a secondary analysis from the Malawi CPAP IMPACT trial evaluating risk factors for antibiotic failure among children hospitalized with pneumonia.MethodsParticipants were 1-59 months old with World Health Organization-defined severe pneumonia and hypoxemia, severe malnutrition, and/or HIV exposure/infection. All participants received intravenous antibiotics per standard care. First-line antibiotics were benzylpenicillin and gentamicin for five days. Study staff assessed patients for first-line antibiotic failure daily between days 3-6. When identified, patients failing antibiotics were switched to second-line ceftriaxone. Analyses excluded children receiving ceftriaxone and/or deceased by hospital day two. We compared characteristics between patients with and without treatment failure and fit multivariable logistic regression models to evaluate associations between treatment failure and admission characteristics.ResultsFrom June 2015-March 2018, 644 children were enrolled and 538 analyzed. Antibiotic failure was identified in 251 (46.7%) participants, and 19/251 (7.6%) died. Treatment failure occurred more frequently with severe malnutrition (50.2% (126/251) vs 28.2% (81/287), p<0.001) and amongst those dwelling ≥10km from a health facility (22.3% (56/251) vs 15.3% (44/287), p = 0.026). Severe malnutrition occurred more frequently among children living ≥10km from a health facility than those living <10km (49.0% (49/100) vs 35.7% (275/428), p = 0.014). Children with severe malnutrition (adjusted odds ratio (aOR) 2.2 (95% CI 1.52, 3.24), p<0.001) and pre-hospital antibiotics ((aOR 1.47, 95% CI 1.01, 2.14), p = 0.043) had an elevated aOR for antibiotic treatment failure.ConclusionSevere malnutrition and pre-hospital antibiotic use predicted antibiotic treatment failure in this high-risk severe pneumonia pediatric population in Malawi. Our findings suggest addressing complex sociomedical conditions like severe malnutrition and improving pneumonia etiology diagnostics will be key for better targeting interventions to improve childhood pneumonia outcomes.

Project description:BackgroundPneumonia remains the leading cause of paediatric infectious mortality globally. Treatment failure, which can result from non-adherence to oral antibiotics, can lead to poor outcomes and therefore improving adherence could be a strategy to reduce pneumonia related morbidity and mortality. However, there is little published evidence from low-resource settings for the drivers of non-adherence to oral antibiotics in children.ObjectiveWe aimed to investigate reasons for adherence and non-adherence in children diagnosed and treated in the community with fast-breathing pneumonia in rural Malawi.MethodsWe conducted focus group discussions (FGDs) with caregivers of children known to have been diagnosed and treated with oral antibiotics for fast-breathing pneumonia in the community and key informant interviews with community healthcare workers (CHW). FGDs and interviews were conducted within communities in Chichewa, the local language. We used a framework approach to analyze the transcripts.ResultsWe conducted 4 FGDs with caregivers and 10 interviews with CHWs. We identified four themes, which were common across caregivers and CHWs: knowledge and understanding, effort, medication perceptions and community influences. Caregivers and CHWs demonstrated good knowledge of pneumonia and types of treatment, but caregivers showed confusion around dosing and treatment durations. Effort was needed to seek care, prepare medication and understand regimens, acting as a barrier to adherence. Perceptions of how well the treatment was working influenced adherence, with both quick recovery and slow recovery leading to non-adherence. Community influences were both supportive, with transport assistance for referrals and home visits to improve adherence, and detrimental, with pressure to share treatments.ConclusionAdherence to oral antibiotic treatment for fast-breathing pneumonia was understood to be important, however considerable barriers we described within this rural low-resource setting, such as the effort preparing and administering medication, community pressures to share drugs and potential complexity of regimens.

Project description:BackgroundPneumonia is the leading cause of mortality in under-five children and most of these deaths occur in South-East Asia and Africa. Fast breathing pneumonia if not treated can progress to lower chest indrawing pneumonia. Treatment recommendation by the World Health Organization (WHO) for fast-breathing pneumonia includes oral amoxicillin and cotrimoxazole (as an alternative). Due to limited access to health care facilities and skilled health care workers, many children are unable to receive antibiotics. Algorithm-based community case management of pneumonia through trained community health workers has resulted in a decline in morbidity and mortality in low- and middle-income countries (LMIC).MethodsIt was a cluster-randomized, unblinded, community-based trial conducted in the Matiari district of Sindh province, Pakistan. Lady Health Workers (LHWs) were trained in assessing, classifying, and managing fast-breathing pneumonia cases (Respiratory rate of >50 breaths/min) at home with oral amoxicillin for three days and with co-trimoxazole for five days in the intervention and control arms respectively. Children with fast-breathing pneumonia were screened by LHWs and were validated by the study by Community Health Workers (CHWs) within 48 hours. They were followed by the LHWs on days 2, 4, and 14 in intervention and on days 2, 6, and 14 in the control arm. Primary treatment failure was assessed on day 4 in intervention and day 6 in the control arm. A severe pneumonia trial was registered with ClinicalTrials.gov, number NCT01192789.ResultsFrom February 2008 to March 2010, a total of 5876 children were enrolled by Lady Health Workers as fast breathing pneumonia. On validation visits of the CHWs, 728 (12%) children were excluded. A total of 4984 children were analysed as per protocol: 2480 in intervention and 2504 in control. There were 72 (2.9%) primary treatment failures in the intervention arm as compared to 102 (4%) in the control arm with a risk difference of -0.94 (-2.84%, 0.96%). Secondary treatment failures were almost equal in both arms (4 vs 7 cases). No deaths or serious adverse events were recorded.ConclusionsThis study shows that amoxicillin can be as effective as cotrimoxazole to treat fast-breathing pneumonia cases at the domiciliary level.RegistrationNCT01192789.

Dataset Information

Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.

Publications

Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.

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