Bacteraemia in Malawian neonates and young infants 2002–2007: a retrospective audit

OBJECTIVES: To assess the causes of bacteraemia in young infants and susceptibility to first-line antibiotics (benzylpenicillin plus gentamicin) at the Queen Elizabeth Central Hospital (QECH), Malawi during 2002-2007. DESIGN: Retrospective analysis of demographic and microbiological data using laboratory records. SETTING: QECH is Malawi's largest hospital with 7000 neonates admitted annually, 9% for septicaemia. PATIENTS: All infants aged 60 days or less admitted to QECH that had a blood culture taken over the 6-year period. MAIN OUTCOME MEASURES: 6754 blood cultures were taken. 3323 organisms were isolated: one-third were pathogens, two-thirds contaminants. Gram-positive organisms (53%) were more common than gram-negatives (47%). Four organisms made up half of all pathogens: Staphylococcus aureus (15.3%), group B streptococci (13.5%), non-typhoidal salmonellae (12.6%) and Escherichia coli (10.5%). Apart from non-typhoidal salmonellae and Streptococcus pneumoniae, most organisms were more common in the first week of life than later. Overall, 28% of isolates during 2002-2007 were resistant to first-line antibiotic, higher than observed during 1996-2001 (22%). Penicillin susceptibility fluctuated while gram-negative resistance to gentamicin increased from 17% to 27% over the study period. CONCLUSIONS: In the QECH, pathogens causing young infant sepsis are an unusual mix of organisms seen in both developed and developing countries. Resistance to first-line antibiotics is higher than observed in most studies. Ongoing monitoring is needed and clinical outcome data would aid interpretation of findings. A high proportion of blood cultures were contaminated with skin flora-improved training and supervision of phlebotomists are needed to improve the utility of taking blood cultures

Stavudine toxicity in adult longer-term ART patients in Blantyre, Malawi

BACKGROUND: Stavudine is an effective and inexpensive antiretroviral drug, but no longer recommended by WHO for first-line antiretroviral regimens in resource-limited settings due to toxicity concerns. Because of the high cost of alternative drugs, it has not been feasible to replace stavudine in most adults in the Malawi ART programme. We aimed to provide policy makers with a detailed picture of stavudine toxicities in Malawians on longer-term ART, in order to facilitate prioritization of stavudine replacement among other measures to improve the quality of ART programmes. METHODS: Prospective cohort of Malawian adults who had just completed one year of stavudine containing ART in an urban clinic, studying peripheral neuropathy, lipodystrophy, diabetes mellitus, high lactate syndromes, pancreatitis and dyslipidemia during 12 months follow up. Stavudine dosage was 30 mg irrespective of weight. Cox regression was used to determine associations with incident toxicities. RESULTS: 253 patients were enrolled, median age 36 years, 62.5% females. Prevalence rates (95%-confidence interval) of toxicities after one year on stavudine were: peripheral neuropathy 21.3% (16.5-26.9), lipodystrophy 14.7% (2.4-8.1), high lactate syndromes 0.0% (0-1.4), diabetes mellitus 0.8% (0-2.8), pancreatitis 0.0% (0-1.5). Incidence rates per 100 person-years (95%-confidence interval) during the second year on stavudine were: peripheral neuropathy 19.8 (14.3-26.6), lipodystrophy 11.4 (7.5-16.3), high lactate syndromes 2.1 (0.7-4.9), diabetes mellitus 0.4 (0.0-1.4), pancreatitis 0.0 (0.0-0.2). Prevalence of hypercholesterolemia and hypertriglyceridemia increased from 12.1% to 21.1% and from 29.5% to 37.6% respectively between 12 and 24 months. 5.5% stopped stavudine, 1.3% died and 4.0% defaulted during follow up. Higher age was an independent risk factor for incident peripheral neuropathy and lipodystrophy. CONCLUSION: Stavudine associated toxicities continued to accumulate during the second year of ART, especially peripheral neuropathy and lipodystrophy and more so at increasing age. Our findings support investments for replacing stavudine in first-line regimens in sub-Saharan Africa

Time to first stavudine toxicity (peripheral neuropathy, lipodystrophy, high lactate syndrome, pancreatitis or diabetes) in patients starting the second year of stavudine containing ART without any of these toxicities.

<p>Time to first stavudine toxicity (peripheral neuropathy, lipodystrophy, high lactate syndrome, pancreatitis or diabetes) in patients starting the second year of stavudine containing ART without any of these toxicities.</p

Study diagram.

<p>Study diagram.</p

Analysis of changes in serum lipid levels over time.

<p>TC, total cholesterol; LDL-c, low density lipoprotein cholesterol; HDL-c, high density lipoprotein cholesterol; TG, triglyceride.</p>*<p>At the time of enrolment into the study, after 12 months of stavudine containing ART.</p

Prevalence rates at enrolment and incidence rates during 12 months of follow up of stavudine associated toxicities in 253 Malawian adults.

*<p>Prevalence at enrolment i.e. after one year of stavudine containing ART.</p>¶<p>One or more of peripheral neuropathy, lipodystrophy, pancreatitis, hyperlactate syndrome, diabetes mellitus.</p>†<p>severe hyperlactatemia, symptomatic hyperlactatemia and lactic acidosis, as defined in methods paragraph.</p><p>IR, incidence rate; PR, prevalence rate; CI, confidence interval; py, person-years; TC, total cholesterol serum level; TG, triglyceride serum level.</p

Patient characteristics.

<p>All characteristics are expressed as n (%) and are measured at enrolment, unless otherwise indicated.</p><p>All characteristics are at enrolment into the study (after one year on ART), except WHO stage and CD4 count as indicated.</p><p>IQR, inter-quartile range; BMI, body mass index; ART, antiretroviral therapy; WHO, world health organization; TB, tuberculosis; KS, Kaposi's sarcoma; eCC, estimated creatinine clearance (Cockroft-Gault method).</p

Cox regression models of variables associated with stavudine associated side effects.

¶<p>One or more of peripheral neuropathy, lipodystrophy, pancreatitis, high lactate syndrome, diabetes mellitus.</p><p>HR, hazard ratio; aHR, adjusted hazard ratio; CI, confidence interval, BMI, body mass index; WHO, world health organization; TB, tuberculosis;</p><p>eCC, estimate creatinine clearance.</p>*<p>WHO stage refers to being in WHO clinic stage 3 or 4 vs. being in stage 1 or 2 at the start of ART. Significant associations are indicated in bold font.</p>†<p>TB diagnosis refers to previous and current diagnosis.</p