Three regimens of procaine penicillin G, Augmentin, and probenecid compared for treating acute gonorrhoea in men.
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Abstract:
The efficacy of three penicillin regimens in treating uncomplicated gonorrhoea in men was evaluated. The regimens consisted of: Augmentin 3.25 g plus probenecid 1 g orally: aqueous procaine penicillin G 4.5 MIU intramuscularly and probenecid 1 g plus one tablet of Augmentin 375 mg orally; or aqueous procaine penicillin G 4.5 MIU intramuscularly and probenecid 1 g plus two tablets of Augmentin 375 mg orally. Cure rates for infections caused by penicillinase (beta lactamase) producing Neisseria gonorrhoeae (PPNG) were 87% (20/23) for regimen 1, 97% (28/29) for regimen 2, and 95% (19/20) for regimen 3. Thus the addition of one or two tablets of Augmentin 375 mg to aqueous procaine penicillin G and probenecid cured 96% (47/49) of infections caused by PPNG strains. All three regimens were 100% effective in eradicating infections caused by non-PPNG strains. Post gonococcal urethritis occurred in 24% of cases treated with regimen 1, 14% of cases treated with regimen 2, and 15% of cases treated with regimen 3. The geometric minimum inhibitory concentrations (MIC90) of Augmentin for 72 PPNG and 162 non-PPNG isolates of N gonorrhoeae obtained before treatment were 1.98 and 0.55 mg/l, respectively. Regimen 2, besides being effective against infections caused by PPNG or non-PPNG strains, has the advantage of cost effectiveness and low toxicity. This regimen may be useful in treating gonorrhoea in areas of high prevalence of PPNG strains, such as South East Asia and Africa.Keywords:
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Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL. (JAMA1981;246:2583-2584)
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Cerebrospinal fluid and serum penicillin levels were determined in patients with latent syphilis. Mean serum concentration one week after the third weekly dose of 2.4 million units penicillin G benzathine was 0.32 units/mL. Concurrent administration of probenecid orally produced a mean serum penicillin level of 0.41 units/mL. Doubled penicillin doses without and with daily orally administered probenecid resulted in mean serum concentrations of 0.75 and 1.00 units/mL, respectively. Two of six patients in the last group had CSF penicillin concentrations greater than 0.03 units/mL.
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Paired specimens of cerebrospinal fluid and serum were taken from 21 patients to estimate penicillin concentrations two to three hours after the last dose of a course of 14-21 daily intramuscular injections of procaine penicillin 0.6 MU. Of 10 patients treated with procaine penicillin alone, eight had no detectable penicillin and two had sub-treponemicidal concentrations (less than 0.018 mg/l) in the cerebrospinal fluid. Of 11 patients treated with procaine penicillin as above and probenecid 2 g a day by mouth, three had no detectable penicillin, two had sub-treponemicidal concentrations, and six had treponemicidal concentrations of penicillin in the cerebrospinal fluid. All 21 patients had treponemicidal concentrations of penicillin in the serum. This dose of procaine penicillin alone or with probenecid is therefore not recommended for treating neurosyphilis.
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An effective single-dose, oral treatment for gonorrhoea would help to relieve pressure in a staff-starved specialty coping with busy clinics, especially if it also reduced the incidence of subsequent non-gonococcal urethritis (NGU) in males.NGU after cure of gonorrhoea is not uncommon.Csonka (1967) found an incidence of 22 per cent.after effective penicillin treatment of gonorrhoea but only 6 per cent.when tetracycline was used.Penicillin has little, if any, effect on NGU.The cure rate obtained in gonorrhoea treated with procaine penicillin varies from country to country and even in the same area from time to time.This varying success is due to the prevalence of relatively insensitive strains of N. gonorrhoeae and such strains require a higher level of penicillin if cure is to be obtained.Ampicillin is acid-stable, absorption after oral administration is good and little influenced by food, and it is relatively cheap, and non-toxic; an oral dose of 1 g.produces a peak plasma level after 2 hrs of about 6 ptg./ml. (Goodman and Gilman, 1970).Normally about one-quarter of an oral dose is cleared by the kidney in the first 12 hrs, but this excretion can be reduced and delayed by the con- current use of probenecid.Ampicillin is bactericidal during the logarithmic growth phase of N. gonorrhoeae so it is important to prolong the period of an effective level of penicillin in the plasma.From Denmark, Br0-Jorgensen and Jensen (1971) reported a failure rate of only 1 9 per cent.using this combined treat- ment.It was, therefore, decided to evaluate the efficacy of a single oral treatment combining ampicillin and probenecid. Material and methodsAlternate male patients with gonorrhoea, in a series of 252 consecutive cases, were treated either with one intra- muscular injection of 1-2 m.u.aqueous procaine penicillin or with 1 g.ampicillin plus 1 g.probenecid swallowed with water under supervision in the clinic.The diagnosis was based on Gram-stained smears and culture of urethral
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Summary Six hundred and thirteen male patients with acute uncomplicated gonorrhoea have been treated alternately with single injections of 1·2 mega-units of aqueous procaine penicillin alone or with the same dose and preparation of penicillin with an additional 1·0 g of probenecid given orally immediately prior to injection. Whether the failure rates were assessed on the basis of an absence of further sexual exposure or by classifying all recurrences within 1 or 2 weeks regardless of history as treatment failures the results were significantly better when probenecid was also given. The use of a single dose of probenecid is thus capable of maintaining the success of single injection procedures for the treatment of gonorrhoea based on procaine penicillin and thus represents a bulwark for the future should the powers of penicillin against the gonococcus in London deteriorate further.
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(1952). Influence of probenecid on serum penicillin concentration after oral administration of penicillin. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 4, No. 2, pp. 83-88.
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