627

Correspondence

References Eidus, L., Harnanansingh, A. M. T. & Jessamine, A. G. Urine test for phenotyping isoniazid inactivators. American Review of Respiratory Disease 104: 587-91 (1971). Eidus, L. & Hodgkin, M. M. Screening of isoniazid inactivators. Antimicrobial Agents and Chemotherapy 3: 130-3 (1973). Eidus, L., Hodgkin, M. M., Hsu, A. H. E. & Schaefer, O. Pharmacokinetic studies with an isoniazid slow-releasing matrix preparation. American Review of Respiratory Disease 110: 34-42 (1974a). Eidus, L., Hodgkin, M. M., Schaefer, O. & Jessamine, A. G. Distribution of isoniazid inactivators determined in Eskimos and Canadian college students by a urine test. Revue Canadienne de biologie 33:117-23 (19746). Eidus, L., Pollak, B., Karagoz, A. & Hodgkin, M. M. La chimioth6rapie intermittente de la tuberculose: une etude des problemes impliquds et compte rendu des contributions faites recemment au Canada. U Union Midicale du Canada 103:1271-4 (1974c). Eidus, L. & Hodgkin, M. M. A new isoniazid preparation designed for moderately fast and 'fast' metabolizers of the drug. ArzneimittelForschung {Drug Research) 25: 1077-80 (1975). Jeanes, C. W. L., Schaefer, O. & Eidus, L. Inactivation of isoniazid by Canadian Eskimos and Indians. Canadian Medical Association Journal 106: 331-5 (1972). Vivien, J. N., Thibier, R. & Lepeuple, A. Recent studies on isoniazid. Advances in Tuberculosis Research 18: 148-230 (1972). Cephradine treatment of typhoid fever Sir, Having read the leading article 'The antibiotic treatment of typhoid fever' (Geddes, 1977) we would like to draw the author's attention to the studies carried out in the Departments

of Experimental Pharmacology and Hygiene of the Medical School of the University of Thessaloniki and the Hospital for Infectious Diseases of Thessaloniki, Greece. We found that 10 strains of Salmonella typhi resistant to chloramphenicol (MIC 60 ng/ml) were susceptible to cephradine with a MIC 0 1 5 ug/ml (Paradelis & GrigoriadouEdipides, 1976). These strains were isolates from patients of Middle East origin admitted to the Hospital for Infectious Diseases. Cephradine was used in these cases with promising results, however further studies are considered desirable. In another in vitro study of 49 blood and faeces isolates of S. typhi we found MICs for cephradine ranging from 0-078 to 1-25 ug/ml. On the other hand the MICs for chloramphenicol and ampicillin ranged from 0-625 to 500 ug/ml and from 0156 to 500 ug/ml respectively (Paradelis et al., 1977). Another case of Salmonellosis was also treated successfully with cephamandol, a new cephalosporin derivative (Hirschman et al., 1977). A. G. PARADELIS G. STATHOPOULOS A. GRIGORIAJDOU-EDIPIDES Departments of Experimental Pharmacology and Hygiene, Medical Faculty, Aristotelian University of Thessaloniki, Greece References Geddes, A. M. The antibiotic treatment of typhoid fever. Journal of Antimicrobial Chemotherapy 3: 382-383 (1977). Hirschman, S. Z., Meyers, T. B. & Miller, A. Antimicrobial activity of cephamandol against solmonella typhi. Antimicrobial Agents and Chemotherapy 11: 369-372 (1977). Paradelis, A. G. & Grigoriadou-Edipides, A. Susceptibility of Salmonella typhosa and Salmonella typhimurium resistant to chloramphenicol. Abstracts of the Annual Meeting—1976 (A 19). American Society for Microbiology. Paradelis, A. G., Grigoriadou-Edipides, A., Edipides, T. & Logaras, G. Susceptibility of Salmonella typhi to cephradine, ampicillin and chloramphenicol. Abstracts of Annual Meeting— 1977 (A 30). American Society for Microbiology. Effect of probenecid on serum cefoxitin concentrations Sir, Cefoxitin, a new P-lactamase stable cephamycin, has been shown in recent early clinical

Downloaded from http://jac.oxfordjournals.org/ at New York University on June 11, 2015

are employing different timings, they are deviating from our method. Accordingly they would have to select difTerent index values for the division of the two groups of inactivators. In our test it is crucial to observe the exact collection period in order to render the result reproducible. A clarification of this point in Dr Gangadharam's Correspondence will avoid an erroneous interpretation of the 'inactivation index' recommended by us. LESLIE EDDUS M. M. HODGKIN Bureau of Bacteriology, Laboratory Centre for Disease Control, Health and Welfare Canada, Ottawa, Ontario, Canada

628

Correspondence

tageous to use probenecid is however debatable because it has been shown that the principal effect of probenecid in producing enhanced serum concentrations of penicillins and cephalosporins is to decrease the apparent volume of distribution of the drug (Gibaldi & Schwartz, 1968). It is therefore possible that in some tissues serum antibiotic concentrations would not necessarily be enhanced. Further investigations of the pharmacokinetic mechanisms of probenecid action are required. A. J. BINT D. S. REEVES H. A. HOLT Department of Medical Microbiology, Southmead Hospital, Bristol, England References Bint, A. I , Holt, A. H., Reeves, D. S. & Stocks, P. J. Clinical experience with cefoxitin. Proceedings of the 10th International Congress of Chemotherapy (Zurich), in press. Geddes, A. M., Schnurr, L. P., McGhie, D., Brookes, G. R., Wise, R. & Andrews, J. Cefoxitin: a hospital study. British Medical Journali: 1126-8(1977). Gibaldi, M. Schwartz, M. A. Apparent effect of probenecid on the distribution of penicillins in man. Clinical Pharmacology and Thesapeutics 9: 345-9 (1968). Goodwin, C. S., Raftery, E. B., Goldberg, A. D., Skeggs, H., Till, A. E. & Martin, C. M. Effects of rate of infusion and probenecid on serum levels, renal excretion and tolerance of intravenous doses of cefoxitin in humans: comparison with cephalothin. Antimicrobial Agents and Chemotherapy 6: 338^6 (1974). Heseltine, P. N. R., Busch, D. F., Meyer, R. D. & Finegold, S. Cefoxitin: clinical evaluation in thirty-eight patients. Antimicrobial Agents and Chemotherapy 11: 427-34 (1977).

Downloaded from http://jac.oxfordjournals.org/ at New York University on June 11, 2015

trials to be a promising agent in a variety of infections, particularly gut-associated sepsis (Geddes tt al., 1977; Heseltine, Busch, Meyer & Finegold, 1977). We have treated a patient in our cefoxitin trial with probenecid and wish to report its effect on the serum cefoxitin concentrations. The patient, a 24-year-old female with non-streptococcal puerperal sepsis and normal renal function was given cefoxitin 2 g 8-hourly by short bolus intravenous injection over 5 min. On day 2 of therapy serum cefoxitin concentrations at 2, 4 and 7-5 h after a dose were 22-8 mg/1, 2-7 mg/1 and < 1 mg/1 respectively. Probenecid 1 g orally 8-hourly was started on day 3 of therapy and on day 4 serum cefoxitin concentrations at times corresponding to those measured previously were 74-2 mg/1, 390 mg/1 and 11-7 mg/1. Serum half-lives of cefoxitin calculated from both sets of serum concentrations are 39 min before probenecid and 129 min during probenecid treatment; the serum half-life was thus increased by a factor of 3-3. The patient made a complete recovery from her infection. Our data is similar to that of Goodwin et al. (1974) who found that the mean serum half-life of cefoxitin in volunteers was prolonged from 41 min to 83 min by pretreatment with a single 1 g dose of probenecid given intravenously. There is currently discussion about appropriate dosage schedules for cefoxitin (Bint, Holt, Reeves & Stocks, in press). We feel that a dose interval of 8 h is probably too long, certainly for young patients with normal renal function, because adequate serum concentrations are only maintained for about 2 h. It is clear that probenecid has a substantial effect on serum cefoxitin concentrations causing them to be adequately maintained for perhaps 8 h. Whether it would be advan-

Effect of probenecid on serum cefoxitin concentrations.

627 Correspondence References Eidus, L., Harnanansingh, A. M. T. & Jessamine, A. G. Urine test for phenotyping isoniazid inactivators. American Revi...
147KB Sizes 0 Downloads 0 Views