Does antibiotic resistance kill children with blood infections?
In a Tanzanian children's hospital, bloodstream infections that the standard antibiotics could not treat because of resistance independently predicted death.
Source
Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study
Study at a glance
- Design
- Cohort — Prospective one-year cohort of admitted children with suspected systemic infection; blood culture, susceptibility testing, malaria smear and HIV test at admission; logistic regression for in-hospital death
- N
- N=1787 · 1787 children (1828 admissions) at Muhimbili National Hospital, Dar es Salaam; regression models used 1527 suspected-infection cases and 216 culture-confirmed bloodstream infections with complete data
- Population
- Children aged 0-7 years admitted with fever, hypothermia or other signs of systemic infection, August 2001 to August 2002
- Outcome
- In-hospital death; secondary: length of stay, pathogens and antimicrobial resistance patterns
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What they did
Over one year, doctors at Tanzania's national hospital enrolled every child up to age 7 admitted with signs of serious infection, took a blood culture, a malaria smear and an HIV test, and recorded treatment and outcome. Bacteria and fungi grown from blood were tested for antibiotic susceptibility, so the team could tell whether the drugs a child actually received matched the organism. Logistic regression then identified which factors (pathogen type, inappropriate treatment, HIV, malnutrition, malaria and others) independently predicted in-hospital death.
What they found
Culture-confirmed bloodstream infection occurred in 13.9% of admissions and tripled the risk of dying; mortality with Gram-negative bloodstream infection (45.6%) was more than twice that with malaria (20.2%). Gram-negative bacteria were often resistant to the usual drugs (only 20% of community-acquired Enterobacteriaceae were ampicillin-sensitive, and 18% of Enterobacteriaceae produced ESBLs), and receiving antibiotics that did not cover the organism independently predicted death, as did HIV infection and malnutrition. Among survivors, inappropriate treatment was linked to a longer hospital stay (median 8 versus 6 days).
The limits
What it doesn't show
Most children (67.2%) had already received antibiotics before blood was cultured, and only one small-volume culture was taken without anaerobic culture, so infections with easily killed organisms such as pneumococci were probably missed and the pathogen mix is skewed toward resistant bacteria. Outcome data were missing for about a tenth of admissions and HIV status for about half of children. As an observational single-hospital study, 'inappropriate treatment' may partly reflect sicker children or harder-to-treat organisms rather than resistance alone, and the hospital-acquired label depended on timing that could misclassify cases.
Key terms
- Bloodstream infection (bacteraemia/fungaemia)
- Infection confirmed by growing a disease-causing bacterium or fungus from a blood culture.
- Inappropriate antimicrobial treatment
- Treatment with drugs to which the child's isolated organism was not susceptible in laboratory testing.
- ESBL (extended-spectrum beta-lactamase)
- Bacterial enzymes that destroy most penicillins and cephalosporins, leaving few treatment options.
- Community- vs hospital-acquired infection
- Infection present on admission (culture within 48 hours) versus infection likely caught in hospital.
- Independent risk factor
- A factor still associated with the outcome after statistically adjusting for other measured factors in a multivariable model.
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What type of study was this?
Common questions
Why compare bloodstream infection with malaria?
The two look nearly identical at the bedside, and malaria is cheap to treat; showing that Gram-negative bloodstream infection killed far more children highlights the danger of assuming fever means malaria.
Does this prove resistance causes deaths?
It shows a strong independent association after adjusting for measured factors like HIV and malnutrition, but residual confounding by illness severity is possible in an observational study.
Why might pneumococcal infections be under-counted?
Many children had antibiotics before culture, blood volumes were small, and human-blood agar used in the lab performs poorly for growing pneumococci.
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