Correspondence
525
Downloaded from http://jac.oxfordjournals.org/ at Simon Fraser University on May 29, 2015
Johnson, F. W. A. & Hobson, D. A method for testing the antibiotic susceptibility of Chlamydia trachomatis in a cell culture system. Journal of Antimicrobial Chemotherapy 3: 49-56 (1977). Rees, E. & Hobson, D. Sticky eye in the newborn. British Medical Journal iv: 656-7 (1974). Reeve, P. The inactivation of Chlamydia trachomatis by povidone-iodine. Journal of Antimicrobial Chemotherapy 2: 77-80 (1976). Richmond, S. J. The isolation of Chlamydia subgroup A {Chlamydia trachomatis) in irradiated McCoy cells. Journal of Medical Laboratory Technology 31: 7-9 (1974). Richmond, S. J., Hilton, A. L. & Clarke, S. K. R. 10 15 20 25 30 Role of Chlamydia subgroup A in non-gonoTime (min) coccal and post-gonococcal urethritis. British Figure 1. Effect of time and temperature on the Journal of Venereal Diseases 48: 437-44 inactivation of T181 by 22-5 ug chlorhexidine/ml. (1972). IFU, inclusion-forming units. Symbols: O, control Richmond, S. J. & Sparling, P. F. Genital solutions in sterile deionized water, 10 min sample chlamydial infections. American Journal of at 35°C, 30 min sample at room temperature; Epidemiology 103: 428-35 (1976). • , chlorhexidine at room temperature; A, chlor- Ridgway, G. L., Owen, J. M. & Oriel, J. D. A hexidine at 35°C. method for testing the antibiotic susceptibility of Chlamydia trachomatis in a cell culture system. Journal of Antimicrobial Chemotherapy 2: 71-6 1962; Gordon & Quan, 1972; Ridgway, Owen (1976). & Oriel, 1976; Johnson & Hobson, 1977). This work shows that antiseptic substances Sompolinsky, D. & Richmond, S. J. Growth of Chlamydia trachomatis in McCoy cells treated can be tested similarly. The more laborious with Cytochalasin B. Applied Microbiology 28: method of growing chlamydiae in ovo, previ912-14 (1974). ously used to assess the antichlamydial activity of the antiseptic povidone-iodine (Reeve, 1976), can therefore be avoided. Inhibition of (3-lactamase: synergistic bactericidal effect of combination of chloramnhenicolcephaloridine Acknowledgements Sir, We are grateful to Mr Vivian Annett for expert technical assistance and to Dr Suzanne In relation to the leading article by Dr Hamilton-Miller entitled 'Inhibition of PK. R. Clarke for helpful comments. lactamase: a continuing story' [Journal of SHIRLEY J. RICHMOND Antimicrobial Chemotherapy 3: 195-6 (1977)] Public Health Laboratory, we would like to draw your attention to yet Myrtle Road, Kingsdown, another mechanism of inhibition which we Bristol BS2 8EL, England described recently (Michel, Bornstein, Luboshitzky & Sacks, 1975; Michel, Jacobs & Sacks, 1977). This synergistic bactericidal References effect of chloramphenicol and P-lactams, due Bernkopf, H., Mashiah, P. & Becker, Y. Sus- to chloramphenicol-induced inhibition of ceptibility of a trachoma agent grown in FL cell P-lactamase production was described as an cultures to the action of antibiotics and a sulfa in vitro phenomenon. We recently encountered drug. Proceedings of the Society for Experi- two patients in whom it seemed justifiable to mental Biology and Medicine 111: 61-7 (1962). use this combination in vivo. In both cases the Gordon, F. B. & Quan, A. L. Susceptibility of Chlamydia to antibacterial drugs: tests in cell synergistic effect was demonstrated in vitro cultures. Antimicrobial Agents and Chemo- on the causative organism before the clinical use was considered, and in both patients the therapy 2: 242-4 (1972). Hilton, A. L., Richmond, S. J., Milne, J. D., isolated organism was multiply resistant, and Hindley, F. & Clarke, S. K. R. Chlamydia A in the infections had failed to respond to other the female genital tract. British Journal of antibiotics used singly or in combinations. Venereal Diseases 50: 1-10 (1974). The first patient was a 45-year-old woman Johnson, F. W. A. & Hobson, D. Factors affecting the sensitivity of replicating McCoy cells in the who developed an intractable infection with a isolation and growth of chlamydia A (TRIC strain of Proteus rettgeri 4 weeks after kidney transplantation. The organism was highly agents). Journal of Hygiene 76: 441-51 (1976).
526
Correspondence week after stopping the treatment a routine examination showed a massive pyuria, and the culture grew the same strain of Serratia liquefaciens (105/ml). In vitro examination of the strain showed a strong bactericidal effect of the combination of cephaloridine and chloramphenicol. Treatment was started with cephaloridine 1 g x 3/day i.m. and 3 days later, while urine cultures were still positive (Serratia liquefaciens lO'/ml), chloramphenicol was added (3 g/day per os). Two days after the addition of chloramphenicol to the treatment, the urine was sterile. The pyuria diminished progressively and disappeared on the 5th day of combined antibiotic treatment. The treatment was stopped after 10 days, and the urine has now remained sterile for more than 6 months. We do not suggest that the traditional general rule regarding the potential antagonistic action of chloramphenicol and the P-Iactams should be abandoned. On the contrary, we strongly recommend that clinical use of this combination be limited to cases in which: (i) prior in vitro testing demonstrates the synergistic bactericidal action of the combination, (ii) the severity or nature of the infection requires bactericidal treatment and (iii) there is no other therapeutic possibility. The two cases that we have described fulfilled these criteria. In the first, a life-threatening infection was cured where several other regimes had failed. In the second a persistent infection was eradicated by the combination but not by either drug singly. Finally it must be emphasized that the combination is synergistic only when the resistance to the 3-lactam is due to P-lactamase production, and that high concentrations which can only be achieved under special circumstances, are often needed to demonstrate the effect. T. SACKS J. MICHEL Department of Clinical Microbiology
A. DURST Department of Surgery B, Hadassah University Hospital, Jerusalem, Israel
J. STESSMAN Department of Internal Medicine, Shaarei Zedek Hospital, Jerusalem, Israel References Michel, J., Bornstein.H., Luboshitzky, R. & Sacks, T. Mechanism of chloramphenicol-cephalcridine synergism on Enterobacteriaceae. Antimicrobial Agents and Chemotherapy 7: 845-9 (1975).
Downloaded from http://jac.oxfordjournals.org/ at Simon Fraser University on May 29, 2015
resistant (MIC > 500 ng/ml) to ampicillin, carbenicillin, cephaloridine, colistin and tetracycline and to the aminoglycosides streptomycin, gentamicin, tobramycin, kanamycin ( M I O 1 2 5 ug/ml). The MIC of chloramphenicol was 16 ug/ml and the MBC 64 ug/ml. It was isolated repeatedly from urine and the surgical wound. Treatment with cephalothin (9 g/day) and subsequently gentamicin had no clinically or bacteriologically detectable effect. Proteus rettgeri was isolated from the transplanted kidney, which had to be removed after 9 weeks, and on the 9th post-operative day the patient developed clinical signs of septicemia, with repeated blood cultures yielding growth of the resistant Proteus rettgeri. Combined treatment with cotrimoxazole (960 jig/24 h) and colistin methane sulphate (1 million units after each hemodialysis) had no effect and the patient remained critically ill, with continued high fever, chills and positive blood cultures over the next 10 days. On the basis of in vitro demonstration of a synergistic bactericidal effect of the combination of chloramphenicol and cephaloridine, due to chloramphenicolinduced inhibition of the fMactamase produced by this organism, treatment was started with cephaloridine (1 gm/24 h) and chloramphenicol (2 gm/24 h). Defervescence started within 48 h and the patient was afebrile after 72 h. The wound and blood cultures became sterile. The patient's serum repeatedly showed bactericidal activity against the Proteus rettgeri strain at a dilution of 1/8. Antibiotic treatment was stopped after 3 weeks and the patient remained well. She was discharged in a satisfactory condition, and on hemodialysis twice weekly. The second patient was a 69-year-old man with a stone in the left lower renal calyx, who was known to have continuous asymptomatic bacteriuria with a strain of Serratia liquefaciens highly resistant (MIC > 500 ug/ml) to ampicillin, carbenicillin, cephaloridine, colistin, cotrimoxazole, tetracyclines, furadantin, streptomycin, kanamycin, gentamicin and tobramycin. The MIC of chloramphenicol was 32 ug/ml and the MBC 128 ug/ml. During hospitalization for an acute anteroseptal myocardial infarct he developed clinical signs of urinary tract infection with temperature up to 38°C. Repeated urine cultures yielded growth of a strain of Serratia liquefaciens (>105/ml) with the same multiple resistance pattern. The patient received chloramphenicol 3 g/day for 10 days. The urine bacterial count dropped to 10*/ml after 2 days and on the third day the urine was sterile. The pyuria persisted. A
Correspondence Michel, J., Jacobs, J. & Sacks, T. Bactericidal synergistic effect due to chloramphenicol induced inhibition of staphylococcal penicillinase. Chemotherapy 23: 32-6 (1977).
Pharmacokinetic data on single dose of 280 mg gentamicin i.m.
Serum concentrations remained high during the first 6 h following injections. Serum half-life (7^) was 215 ±0-32 h and the elimination constant (Kt) was 0-331 ± 0-055 h"1. The percentage of urinary excretion related to the dosage injected was 35-4 ± 100% during the first 2 h, 600±9-6% during the first 4 h and 85-6±14-2% within 24 h. None of our patients suffered from auditory impairment after injection of gentamicin. Urea and serum creatinine assays made before and 24 h after injection did not vary. Proteinuria was not found when the urine was examined 24 and 48 h after injection of gentamicin. Therefore, in patients with normal renal function, the intramuscular injection of a single dose of 280 mg gentamicin is quite well tolerated clinically and biologically; highest serum concentrations did not exceed permissible limits. Such a regimen could be applied to man when it is considered necessary, but should only be done when renal function is normal. As gentamicin is eliminated through the kidneys, any impairment of renal function will modify pharmacokinetic parameters resulting in an increased peak serum concentration and delayed elimination. Consequently, this therapy has to be used cautiously, otherwise it could become dangerous. C. THUILLIER J. P. FILLASTRE M. GODIN Department ofNephrology, Antibiotic Laboratory, Rouen, France
Table I. Serum concentrations, Tv K. after 280 mg gentamicin single injection in patients with normal renal function Patients ANC BLO DAV DOU HUE LAH LEC MAT RIB THE Mean S.D.
0-25 h
0-50 h
Serum concentrations (jig/ml) 0-75 h 1h 2h 4h
600 12-60 9-35 15-80 15-30 12-20 9-60 3-20 12-60 12-93 12-60 9-60 4-50 7-60 9-68 1300 11-40 7-40 5-70 11-40 5-44 8-92 12-40 1300 12-60 6-30 9-60 9-60 11-86 12-60 3-75 9-20 1212 11-22 10-30 7-50 1212 7-44 11-22 10-30 3-75 8-80 4-50 900 11-44 14-20 6-53 12-25 810 4-20 9-30 11-44 10-20 3 41 3-41 6-82 6-82 1 56 713 9-90 10-38 6-75 9-73 11-48 11-83 511 1-85 2-88 2-86 2-28 2-45 1 38 Mean peak serum concentrations: 12-71 ±1- 57 ug/ml
6h
24h
(hours)
Ke (- 1 )
3-90 I 30 2-48 1 90 2-30 1 80 2-20 3-90 2-50 312 2-54 0-86
0-78 0-78 0-78 0-78 0-78 0-78 0-78 0-78 0-78 0-78
2-49 1-53 1-97 1-93 1-97 200 2-18 2-59 2-39 2-40 215 0-32
0-279 0-453 0-352 0-359 0-352 0-346 0-318 0-268 0-290 0-289 0-331 0055
Downloaded from http://jac.oxfordjournals.org/ at Simon Fraser University on May 29, 2015
Gentamicin is known to have potential ototoxicity and nephrotoxicity when used at high dosage and during a long period. The appearance of Neisseria gonorrhoeae strains only slightly susceptible to penicillins and derivatives has prompted some authors to use gentamicin in single 280 mg injection for the treatment of acute urethritis (Garza Villarreal, 1971; Gomez, 1969; Felarca, Laqui & Ibarra, 1974). Practitioners view such a regimen with caution fearing that too high serum concentrations would occur and result in toxicity. In 10 patients, 4 men and 6 women, with normal renal function, serum and urinary concentrations were studied after intramuscular injections of 280 mg gentamicin. Samples were taken at 0-25, 0-50, 0-75, 1, 2, 4, 6 and 24 h. The urinary bladder was emptied before the injection of gentamicin and urine was collected 0 to 2, 2 to 4, 4 to 6 and 6 to 24 h after the injection. Gentamicin levels were assayed in triplicate by agar plate diffusion, with Bacillus subtilis ATCC 6633 as test strain. Confidence limits of this method are estimated to be within 4 and 66%. The peak serum concentrations (underlined in the table) ranged between 9-90 and 15-8Oug/ ml. The mean value was 12-71 ±1-57 ug/ml.
527
525
Downloaded from http://jac.oxfordjournals.org/ at Simon Fraser University on May 29, 2015
Johnson, F. W. A. & Hobson, D. A method for testing the antibiotic susceptibility of Chlamydia trachomatis in a cell culture system. Journal of Antimicrobial Chemotherapy 3: 49-56 (1977). Rees, E. & Hobson, D. Sticky eye in the newborn. British Medical Journal iv: 656-7 (1974). Reeve, P. The inactivation of Chlamydia trachomatis by povidone-iodine. Journal of Antimicrobial Chemotherapy 2: 77-80 (1976). Richmond, S. J. The isolation of Chlamydia subgroup A {Chlamydia trachomatis) in irradiated McCoy cells. Journal of Medical Laboratory Technology 31: 7-9 (1974). Richmond, S. J., Hilton, A. L. & Clarke, S. K. R. 10 15 20 25 30 Role of Chlamydia subgroup A in non-gonoTime (min) coccal and post-gonococcal urethritis. British Figure 1. Effect of time and temperature on the Journal of Venereal Diseases 48: 437-44 inactivation of T181 by 22-5 ug chlorhexidine/ml. (1972). IFU, inclusion-forming units. Symbols: O, control Richmond, S. J. & Sparling, P. F. Genital solutions in sterile deionized water, 10 min sample chlamydial infections. American Journal of at 35°C, 30 min sample at room temperature; Epidemiology 103: 428-35 (1976). • , chlorhexidine at room temperature; A, chlor- Ridgway, G. L., Owen, J. M. & Oriel, J. D. A hexidine at 35°C. method for testing the antibiotic susceptibility of Chlamydia trachomatis in a cell culture system. Journal of Antimicrobial Chemotherapy 2: 71-6 1962; Gordon & Quan, 1972; Ridgway, Owen (1976). & Oriel, 1976; Johnson & Hobson, 1977). This work shows that antiseptic substances Sompolinsky, D. & Richmond, S. J. Growth of Chlamydia trachomatis in McCoy cells treated can be tested similarly. The more laborious with Cytochalasin B. Applied Microbiology 28: method of growing chlamydiae in ovo, previ912-14 (1974). ously used to assess the antichlamydial activity of the antiseptic povidone-iodine (Reeve, 1976), can therefore be avoided. Inhibition of (3-lactamase: synergistic bactericidal effect of combination of chloramnhenicolcephaloridine Acknowledgements Sir, We are grateful to Mr Vivian Annett for expert technical assistance and to Dr Suzanne In relation to the leading article by Dr Hamilton-Miller entitled 'Inhibition of PK. R. Clarke for helpful comments. lactamase: a continuing story' [Journal of SHIRLEY J. RICHMOND Antimicrobial Chemotherapy 3: 195-6 (1977)] Public Health Laboratory, we would like to draw your attention to yet Myrtle Road, Kingsdown, another mechanism of inhibition which we Bristol BS2 8EL, England described recently (Michel, Bornstein, Luboshitzky & Sacks, 1975; Michel, Jacobs & Sacks, 1977). This synergistic bactericidal References effect of chloramphenicol and P-lactams, due Bernkopf, H., Mashiah, P. & Becker, Y. Sus- to chloramphenicol-induced inhibition of ceptibility of a trachoma agent grown in FL cell P-lactamase production was described as an cultures to the action of antibiotics and a sulfa in vitro phenomenon. We recently encountered drug. Proceedings of the Society for Experi- two patients in whom it seemed justifiable to mental Biology and Medicine 111: 61-7 (1962). use this combination in vivo. In both cases the Gordon, F. B. & Quan, A. L. Susceptibility of Chlamydia to antibacterial drugs: tests in cell synergistic effect was demonstrated in vitro cultures. Antimicrobial Agents and Chemo- on the causative organism before the clinical use was considered, and in both patients the therapy 2: 242-4 (1972). Hilton, A. L., Richmond, S. J., Milne, J. D., isolated organism was multiply resistant, and Hindley, F. & Clarke, S. K. R. Chlamydia A in the infections had failed to respond to other the female genital tract. British Journal of antibiotics used singly or in combinations. Venereal Diseases 50: 1-10 (1974). The first patient was a 45-year-old woman Johnson, F. W. A. & Hobson, D. Factors affecting the sensitivity of replicating McCoy cells in the who developed an intractable infection with a isolation and growth of chlamydia A (TRIC strain of Proteus rettgeri 4 weeks after kidney transplantation. The organism was highly agents). Journal of Hygiene 76: 441-51 (1976).
526
Correspondence week after stopping the treatment a routine examination showed a massive pyuria, and the culture grew the same strain of Serratia liquefaciens (105/ml). In vitro examination of the strain showed a strong bactericidal effect of the combination of cephaloridine and chloramphenicol. Treatment was started with cephaloridine 1 g x 3/day i.m. and 3 days later, while urine cultures were still positive (Serratia liquefaciens lO'/ml), chloramphenicol was added (3 g/day per os). Two days after the addition of chloramphenicol to the treatment, the urine was sterile. The pyuria diminished progressively and disappeared on the 5th day of combined antibiotic treatment. The treatment was stopped after 10 days, and the urine has now remained sterile for more than 6 months. We do not suggest that the traditional general rule regarding the potential antagonistic action of chloramphenicol and the P-Iactams should be abandoned. On the contrary, we strongly recommend that clinical use of this combination be limited to cases in which: (i) prior in vitro testing demonstrates the synergistic bactericidal action of the combination, (ii) the severity or nature of the infection requires bactericidal treatment and (iii) there is no other therapeutic possibility. The two cases that we have described fulfilled these criteria. In the first, a life-threatening infection was cured where several other regimes had failed. In the second a persistent infection was eradicated by the combination but not by either drug singly. Finally it must be emphasized that the combination is synergistic only when the resistance to the 3-lactam is due to P-lactamase production, and that high concentrations which can only be achieved under special circumstances, are often needed to demonstrate the effect. T. SACKS J. MICHEL Department of Clinical Microbiology
A. DURST Department of Surgery B, Hadassah University Hospital, Jerusalem, Israel
J. STESSMAN Department of Internal Medicine, Shaarei Zedek Hospital, Jerusalem, Israel References Michel, J., Bornstein.H., Luboshitzky, R. & Sacks, T. Mechanism of chloramphenicol-cephalcridine synergism on Enterobacteriaceae. Antimicrobial Agents and Chemotherapy 7: 845-9 (1975).
Downloaded from http://jac.oxfordjournals.org/ at Simon Fraser University on May 29, 2015
resistant (MIC > 500 ng/ml) to ampicillin, carbenicillin, cephaloridine, colistin and tetracycline and to the aminoglycosides streptomycin, gentamicin, tobramycin, kanamycin ( M I O 1 2 5 ug/ml). The MIC of chloramphenicol was 16 ug/ml and the MBC 64 ug/ml. It was isolated repeatedly from urine and the surgical wound. Treatment with cephalothin (9 g/day) and subsequently gentamicin had no clinically or bacteriologically detectable effect. Proteus rettgeri was isolated from the transplanted kidney, which had to be removed after 9 weeks, and on the 9th post-operative day the patient developed clinical signs of septicemia, with repeated blood cultures yielding growth of the resistant Proteus rettgeri. Combined treatment with cotrimoxazole (960 jig/24 h) and colistin methane sulphate (1 million units after each hemodialysis) had no effect and the patient remained critically ill, with continued high fever, chills and positive blood cultures over the next 10 days. On the basis of in vitro demonstration of a synergistic bactericidal effect of the combination of chloramphenicol and cephaloridine, due to chloramphenicolinduced inhibition of the fMactamase produced by this organism, treatment was started with cephaloridine (1 gm/24 h) and chloramphenicol (2 gm/24 h). Defervescence started within 48 h and the patient was afebrile after 72 h. The wound and blood cultures became sterile. The patient's serum repeatedly showed bactericidal activity against the Proteus rettgeri strain at a dilution of 1/8. Antibiotic treatment was stopped after 3 weeks and the patient remained well. She was discharged in a satisfactory condition, and on hemodialysis twice weekly. The second patient was a 69-year-old man with a stone in the left lower renal calyx, who was known to have continuous asymptomatic bacteriuria with a strain of Serratia liquefaciens highly resistant (MIC > 500 ug/ml) to ampicillin, carbenicillin, cephaloridine, colistin, cotrimoxazole, tetracyclines, furadantin, streptomycin, kanamycin, gentamicin and tobramycin. The MIC of chloramphenicol was 32 ug/ml and the MBC 128 ug/ml. During hospitalization for an acute anteroseptal myocardial infarct he developed clinical signs of urinary tract infection with temperature up to 38°C. Repeated urine cultures yielded growth of a strain of Serratia liquefaciens (>105/ml) with the same multiple resistance pattern. The patient received chloramphenicol 3 g/day for 10 days. The urine bacterial count dropped to 10*/ml after 2 days and on the third day the urine was sterile. The pyuria persisted. A
Correspondence Michel, J., Jacobs, J. & Sacks, T. Bactericidal synergistic effect due to chloramphenicol induced inhibition of staphylococcal penicillinase. Chemotherapy 23: 32-6 (1977).
Pharmacokinetic data on single dose of 280 mg gentamicin i.m.
Serum concentrations remained high during the first 6 h following injections. Serum half-life (7^) was 215 ±0-32 h and the elimination constant (Kt) was 0-331 ± 0-055 h"1. The percentage of urinary excretion related to the dosage injected was 35-4 ± 100% during the first 2 h, 600±9-6% during the first 4 h and 85-6±14-2% within 24 h. None of our patients suffered from auditory impairment after injection of gentamicin. Urea and serum creatinine assays made before and 24 h after injection did not vary. Proteinuria was not found when the urine was examined 24 and 48 h after injection of gentamicin. Therefore, in patients with normal renal function, the intramuscular injection of a single dose of 280 mg gentamicin is quite well tolerated clinically and biologically; highest serum concentrations did not exceed permissible limits. Such a regimen could be applied to man when it is considered necessary, but should only be done when renal function is normal. As gentamicin is eliminated through the kidneys, any impairment of renal function will modify pharmacokinetic parameters resulting in an increased peak serum concentration and delayed elimination. Consequently, this therapy has to be used cautiously, otherwise it could become dangerous. C. THUILLIER J. P. FILLASTRE M. GODIN Department ofNephrology, Antibiotic Laboratory, Rouen, France
Table I. Serum concentrations, Tv K. after 280 mg gentamicin single injection in patients with normal renal function Patients ANC BLO DAV DOU HUE LAH LEC MAT RIB THE Mean S.D.
0-25 h
0-50 h
Serum concentrations (jig/ml) 0-75 h 1h 2h 4h
600 12-60 9-35 15-80 15-30 12-20 9-60 3-20 12-60 12-93 12-60 9-60 4-50 7-60 9-68 1300 11-40 7-40 5-70 11-40 5-44 8-92 12-40 1300 12-60 6-30 9-60 9-60 11-86 12-60 3-75 9-20 1212 11-22 10-30 7-50 1212 7-44 11-22 10-30 3-75 8-80 4-50 900 11-44 14-20 6-53 12-25 810 4-20 9-30 11-44 10-20 3 41 3-41 6-82 6-82 1 56 713 9-90 10-38 6-75 9-73 11-48 11-83 511 1-85 2-88 2-86 2-28 2-45 1 38 Mean peak serum concentrations: 12-71 ±1- 57 ug/ml
6h
24h
(hours)
Ke (- 1 )
3-90 I 30 2-48 1 90 2-30 1 80 2-20 3-90 2-50 312 2-54 0-86
0-78 0-78 0-78 0-78 0-78 0-78 0-78 0-78 0-78 0-78
2-49 1-53 1-97 1-93 1-97 200 2-18 2-59 2-39 2-40 215 0-32
0-279 0-453 0-352 0-359 0-352 0-346 0-318 0-268 0-290 0-289 0-331 0055
Downloaded from http://jac.oxfordjournals.org/ at Simon Fraser University on May 29, 2015
Gentamicin is known to have potential ototoxicity and nephrotoxicity when used at high dosage and during a long period. The appearance of Neisseria gonorrhoeae strains only slightly susceptible to penicillins and derivatives has prompted some authors to use gentamicin in single 280 mg injection for the treatment of acute urethritis (Garza Villarreal, 1971; Gomez, 1969; Felarca, Laqui & Ibarra, 1974). Practitioners view such a regimen with caution fearing that too high serum concentrations would occur and result in toxicity. In 10 patients, 4 men and 6 women, with normal renal function, serum and urinary concentrations were studied after intramuscular injections of 280 mg gentamicin. Samples were taken at 0-25, 0-50, 0-75, 1, 2, 4, 6 and 24 h. The urinary bladder was emptied before the injection of gentamicin and urine was collected 0 to 2, 2 to 4, 4 to 6 and 6 to 24 h after the injection. Gentamicin levels were assayed in triplicate by agar plate diffusion, with Bacillus subtilis ATCC 6633 as test strain. Confidence limits of this method are estimated to be within 4 and 66%. The peak serum concentrations (underlined in the table) ranged between 9-90 and 15-8Oug/ ml. The mean value was 12-71 ±1-57 ug/ml.
527
