High frequency of antimicrobial resistance in Salmonella and Escherichia coli causing diarrheal diseases at the Yirimadio community health facility, Mali.

BACKGROUND: Diarrhoea is a public health problem, especially in developing countries where it is the second leading cause of child mortality. In Low Income Countries like in Mali, self-medication and inappropriate use of antibiotics due to the scarcity of complementary diagnostic systems can lead to the development of multidrug-resistant bacteria causing diarrhoea. The objective of this work was to determine the microorganisms responsible for diarrhoea in children under 15 years of age and to characterize their sensitivity to a panel of antibiotics used in a peri-urban community in Mali. The study involved outpatient children visiting the Yirimadio Community Health Centre and diagnosed with diarrhoea. Stool samples from those patients were collected and analysed by conventional stools culture and the susceptibility to antibiotics of detected bacteria was determined by the disc diffusion method in an agar medium. RESULT: Overall, 554 patients were included. Children under the age of 3 years accounted for 88.8% (492 of 554) of our study population. Two bacterial species were isolated in this study, Escherichia coli 31.8% (176 of 554) and Salmonella 2.9% (16 of 554). In the 176, E. coli strains resistance to amoxicillin and to cotrimoxazole was seen in 93.8% (165 of 176) and 92.6% ( 163 of 176), respectively. The ESBL resistance phenotype accounted for 39,8% (70 of 176) of E. coli. Sixteen (16) strains of Salmonella were found, of which one strain (6.3%) was resistant to amoxicillin and to amoxicillin + clavulanic acid. Another one was resistant to chloramphenicol (6.3%). Two strains of Salmonella were resistant to cotrimoxazole (12.5%) and two others were resistant to cefoxitin (12.5%). CONCLUSIONS: The data suggest that E. coli is frequently involved in diarrhoea in children under 3 years of age in this peri-urban setting of Bamako, Mali, with a high rate of resistance to amoxicillin and cotrimoxazole, the most widely used antibiotics in the management of diarrhoea in this setting.

Understanding the pharmacokinetics of Coartem.

Artemether and lumefantrine (AL), the active constituents of Coartem exhibit complementary pharmacokinetic profiles. Artemether is absorbed quickly; peak concentrations of artemether and its main active metabolite, dihydroartemisinin (DHA) occur at approximately two hours post-dose, leading to a rapid reduction in asexual parasite mass and a prompt resolution of symptoms. Lumefantrine is absorbed and cleared more slowly (terminal elimination half-life 3-4 days in malaria patients), and accumulates with successive doses, acting to prevent recrudescence by destroying any residual parasites that remain after artemether and DHA have been cleared from the body. Food intake significantly enhances the bioavailability of both artemether and lumefantrine, an effect which is more apparent for the highly lipophilic lumefantrine. However, a meal with only a small amount of fat (1.6 g) is considered sufficient to achieve adequate exposure to lumefantrine. The pharmacokinetics of artemether or lumefantrine are similar in children, when dosed according to their body weight, compared with adults. No randomized study has compared the pharmacokinetics of either agent in pregnant versus non-pregnant women. Studies in healthy volunteers and in children with malaria have confirmed that the pharmacokinetic characteristics of crushed standard AL tablets and the newly-developed Coartem Dispersible tablet formulation are similar. Studies to date in healthy volunteers have not identified any clinically relevant drug-drug interactions; data relating to concomitant administration of HIV therapies are limited. While dose-response analyses are difficult to undertake because of the low rate of treatment failures under AL, it appears that artemether and DHA exposure impact on parasite clearance time while lumefantrine exposure is associated with cure rate, consistent with their respective modes of action. In conclusion, knowledge of the pharmacokinetic profiles of artemether and lumefantrine is increasing within a range of settings, including infants and children. However, additional data would be warranted to better characterize artemether and lumefantrine pharmacokinetics in patients with hepatic impairment, in pregnant women, and in patients undergoing HIV/AIDS chemotherapy.

Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali.

We conducted a randomized single-blinded trial comparing the efficacy and safety of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine-pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali. Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug resistance were determined. After identification of recrudescences by genotyping, both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS + SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001). No significant adverse event attributable to any of the study drugs was found. The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.

A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali.

The choice of artemisinin-based combination that is being adopted for malaria treatment in sub-Saharan Africa may depend on several factors, including cost, efficacy, side effects, and simplicity of administration. We tested the hypothesis that artesunate-sulfamethoxypyrazine-pyrimethamine is as efficacious as the four-dose regimen of artemether-lumefantrine for treatment of Plasmodium falciparum malaria. The study was carried out during two transmission seasons (2003 and 2004) in Sotuba, Mali. Participants at least 6 months of age with uncomplicated P. falciparum malaria were randomly assigned to receive artesunate-sulfamethoxypyrazine-pyrimethamine or artemether-lumefantrine. Treatment efficacy was assessed using the World Health Organization 28-day protocol. A total of 606 (303 in each arm) patients were enrolled. The cure rate was higher for artesunate-sulfamethoxypyrazine-pyrimethamine than for artemether-lumefantrine (98.7% versus 89.6%; P < 0.0001). After correction for cases of re-infection, the cure rates were 100% and 99.0%, respectively (P = 0.08). No serious adverse events occurred. Artesunate-sulfamethoxypyrazine-pyrimethamine is well-tolerated and effective against P. falciparum malaria. It showed an additional benefit of preventing new infections.

Efficacy of chloroquine and sulfadoxine/pyrimethamine for the treatment of uncomplicated falciparum malaria in Koumantou, Mali.

We report the results of an in vivo antimalarial efficacy study with chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) conducted between 2003 and 2004 in Koumantou, southern Mali. A total of 244 children were included in the study; 210 children were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescence from re-infection. Global failure proportions at Day 14, without taking into account re-infections, were 44.2% (95% CI 34.9-53.5%) in the CQ group and 2.0% (95% CI 0.0-4.8%) in the SP group. PCR-adjusted failure proportions at Day 28 were even higher in the CQ group (90.5% (95/105), 95% CI 84.8-96.2%) and relatively low in the SP group (7.0% (7/100), 95% CI 1.9-12.1%). These results show that CQ is no longer efficacious in Koumantou. The use of SP in monotherapy is likely to compromise its efficacy. We recommend the use of artemisinin-based combination therapy as first-line treatment for uncomplicated Plasmodium falciparum malaria in Koumantou.