In vitro activity of rifaximin against bacterial enteropathogens causing diarrhoea in children under 5 years of age in Ifakara, Tanzania

Josep M. Sierraa, Margarita M. Naviaa, Martha Vargasa, Honorati Urassab, David Schellembergb,c, Joaquim Gascónd, Jordi Vilaa and Joaquim Ruiza,*

a Servicio de Microbiología, c Unidad de Epidemiología y Bioestadística and d Unitat Medicina Tropical, Hospital Clínic, IDIBAPS, Barcelona, Spain; b Ifakara Health Research and Development Centre, National Institute for Medical Research, Ifakara, Tanzania

Sir,

Among the bacterial pathogens associated with the development of diarrhoea in children in developing areas, some pathogenic strains of Escherichia coli and Shigella spp. are especially important, because of both the frequency with which they are isolated and the severity of the symptoms they produce.1,2 In developing countries it is common to treat infections empirically. Therefore, knowledge of the local bacterial resistance pattern is a valuable weapon for clinicians in these areas. In Ifakara, as well as in other developing areas, the usual therapy for severe diarrhoea in children is oral rehydration plus an antibiotic, currently co-trimoxazole.

In previous studies carried out in Ifakara, in which the resistance levels of 130 pathogenic E. coli and 86 Shigella spp. were analysed, high rates of resistance, amounting to 100% in some cases, to ampicillin, chloramphenicol, tetracycline and co-trimoxazole were found in the microorganisms studied.1,2 Only quinolones and cephalosporins retained a good activity.1,2 However, neither is a viable alternative because of their high price. Furthermore, quinolones are not recommended for paediatric use.

Rifaximin is a non-absorbable antibacterial agent, reaching high concentrations in the intestinal tract.3,4 Some studies have shown its potential as a treatment for diarrhoea,3 but its activity against clinical isolates from developing areas remains unknown.

The MIC of rifaximin (Alfa Wassermann, Italy) for these previously studied microorganisms was determined by an agar dilution method following the guidelines of the NCCLS.5 E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213 were used as quality controls.

The MIC50 and MIC90 of the three types of diarrhoeagenic E. coli analysed were 8 and 16 mg/L, respectively (TableGo). Moreover, the highest MIC was 32 mg/L (four enteroaggregative E. coli and one enterotoxigenic E. coli), while the MIC50 of all Shigella spp. tested was 4 mg/L, and the MIC90 was 8 mg/L for Shigella flexneri and Shigella dysenteriae, and 16 mg/L for Shigella sonnei (TableGo). No clinical isolate of Shigella showed an MIC > 16 mg/L.


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Table.  Activity of rifaximin against E. coli and Shigella spp.
 
The rates of resistance to rifaximin should not be determined based on the criteria valid for absorbable antibiotics. Blood concentrations achieved after a usual oral dose of rifaximin (400 mg) are always negligible, usually <5 ng/mL (ranging from undetectable values to <25 ng/mL),3,6 whereas the concentrations in the intestinal lumen are much higher. In a study to evaluate its concentration in faeces of travellers after therapy for 3 days with 400 mg of rifaximin every 12 h, it was found that, by the end of the therapy, concentrations of 8000 ± 830 µg/g of rifaximin were achieved in faeces, and 3 days later the concentration was still c. 3000 ± 422 µg/g.5 As the concentration achieved in the intestinal tract remains above the MIC for the strains, rifaximin can be considered as a potential treatment for children with diarrhoea. In fact, in previous studies in which children between 3 and 12 years of age with diarrhoea were treated with rifaximin, satisfactory results were obtained.3

In summary, co-trimoxazole, ampicillin and tetracycline have lost their activity against pathogenic E. coli and Shigella spp. from Ifakara, Tanzania, making it necessary to change the first-line treatment. Rifaximin may be an alternative, although studies evaluating its in vivo activity for the treatment of diarrhoea in children in developing countries should be performed.

Acknowledgments

We thank P. Alonso, C. Menendez and J. J. Aponte (Unit of Epidemiology and Biostatistics, Fundació Clinic, Barcelona) for their useful assistance in the development of this work. This work was performed thanks to a grant by Alfawassermann (Italy). M.V. was supported by a grant from the programme ‘Estancias de investigadores científicos y tecnólogos extranjeros en España’ from the Ministerio de Educación y Cultura.

Notes

J Antimicrob Chemother 2001; 47: 904–905

* Correspondence address. Dept Microbiologia, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. Tel: +34-93-2275522; Fax: +34-93-2275454; E-mail: joruiz{at}clinic.ub.es Back

References

1 .  Navia, M. M., Capitano, L., Ruiz, J., Vargas, M., Urassa, H., Schellemberg, D. et al. (1999). Typing and characterization of mechanisms of resistance in Shigella spp. isolated from feces of children in Ifakara, Tanzania. Journal of Clinical Microbiolology 37, 3113–7.

2 .  Vila, J., Vargas, M., Casals, C., Urassa, H., Mshinda, H., Schellemberg, D. et al. (1999). Antimicrobial resistance of diarrheagenic Escherichia coli isolated from children under the age of 5 years from Ifakara, Tanzania. Antimicrobial Agents and Chemotherapy 43, 3022–4.[Abstract/Free Full Text]

3 .  Gillis, J. C. & Brogden, R. N. (1995). Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs 49, 467–84.[ISI][Medline]

4 .  Jiang, Z. D., Ke, S., Palazzini, E., Riopel, L. & Dupont, H. (2000). In vitro activity and fecal concentration of rifaximin after oral administration. Antimicrobial Agents and Chemotherapy 44, 2205–6.[Abstract/Free Full Text]

5 .  National Committee for Clinical Laboratory Standards. (1997). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically—Fourth Edition; Approved Standard M7-A4. NCCLS, Wayne, PA.

6 .  Descombe, J. J., Dubourg D., Picard, M. & Palazzini, E. (1994). Pharmacokinetic study of rifaximin after oral administration in healthy volunteers. International Journal of Clinical Pharmacology Research 14, 51–6.[ISI][Medline]





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