Current Medical Research and Opinion
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: http://www.tandfonline.com/loi/icmo20
Mezlocillin in gonorrhoea: a pilot study W. Fowler & M. H. Khan To cite this article: W. Fowler & M. H. Khan (1979) Mezlocillin in gonorrhoea: a pilot study, Current Medical Research and Opinion, 5:10, 790-792, DOI: 10.1185/03007997909109015 To link to this article: http://dx.doi.org/10.1185/03007997909109015
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Current Medical Research and Opinion
Vol. 5, No. 10, 1979
Mezlocillin in gonorrhoea: a pilot study
and
W. Fowler, M.D.,
M. H. Khan, M.B.,B.S. Department of Venereal Disease, General Hospital, Birmingham, England
Cum. Med. Res. Opin., (1979), 5,790.
Received : 12th December 1978
Summary A pilot study was carried out in 50 patients with uncomplicated, untreated gonorrhoea to assess the effectiveness of mezlocillin, a new semi-synthetic penicillin. Patients received a single intravenous injection of 2 g mezlocillin and werefollowed-up for periods up to I01 days. Four patients defaulted immediately. Clinical and bacteriologicalfindings showed that only I of the 46patients followed-up had failed to respond to treatment, indicating a cure rate of97.8 %. Five (10.8 %) male patients haddeveloped post-gonococcal urethritis when seen 3 weelcs or later in the follow-up period.
Key words: Mezlocillin - penicillins - gonorrhoea
Introduction The unexpected appearance of beta-lactamase-producing strains of gonococci1. 4 completely resistant to penicillin has tended, for the moment, to obscure the longterm threat to the value of penicillin in gonorrhoea posed by the continuing tendency of non-enzyme-producing strains of gonococci to become increasingly insensitive to this antibiotic. Already, such large increases in the amount of penicillin (5 mu. benzyl penicillin), often with the addition of probenecid,3 have been necessary in some areas to maintain the efficacy of penicillin that it would seem likely that the limit had been reached so far as ‘one shot’ therapy is concerned. This has led to a pilot study of mezlocillin,2.5 a new semi-synthetic penicillin, which has an in vitro spectrum encompassing those of carbenicillin and ampicillin but is much more active against Pseudomonas aeruginosa, Klebsiella, E. coli and Proteus, and exceptionally active against the gonococcus.
Patients and methods Fifty patients (46 male, 4 female) suffering from uncomplicated, untreated gonorrhoea were included in this pilot study. The 4 females were on oral contraceptives. None of the patients were allergic to penicillin or were undergoing treatment for any other condition. Age, marital status, and racial incidence presented no unusual features. The diagnosis was made on the presence of Gram-negative diplococci morphologically identical to gonococcus in films and/or gonococci grown on modified 790
Downloaded by [University of California Santa Barbara] at 09:41 06 November 2015
W. Fowler and M. H . Khan
Thayer-Martin medium. Films and cultures were taken from the urethra in males and from the urethra and cervix in females. In the latter, cultures were also taken from the pharynx and rectum. Sensitivity to penicillin was determined by the disc diffusion method. Any strains showing undue resistance were tested for betalactamase production by the chromogenic cephalosporin 87/312. The fact that this was a pilot study was explained to the patient and consent obtained in writing before the treatment was given. This consisted of 2 g mezlocillin dispersed in 20 ml sterile water slowly injected (1; minutes) into an antecubital vein. Patients were advised t o abstain from sexual intercourse and alcohol for at least 14 days, to attend on the 3 successive days following treatment and then at weekly intervals for 2 weeks, then after 1 month and 2 months. In females, it was proposed t o take films and cultures from the urethra and cervix at each follow-up visit and also from the pharynx and rectum if these sites had been positive initially. In males, the aim was to make films and cultures from any urethral discharge or from urethral scrapings if there was no apparent discharge at the 3 daily visits or within the first 2 weeks but, subsequently, not to take films and cultures unless there were symptoms or clinical evidence (including the state of the urine) to suggest that urethritis was present.
Results The 4 females fulfilled the follow-up schedule. All were cured. Four male patients defaulted immediately and only 9 attended for 3 successive days after treatment. In each case the urethral discharge was still profusely purulent on the day after treatment but had diminished markedly by the third day. Gonococci were not isolated in any of these cases. Details of the full follow-up are shown in the Table I. It will be noted that gonococci were isolated in 2 male cases 14 to 21 days after treatment. I n 1 case there was a history of reinfection. This was denied in the other case but was open to doubt in view of the two previous negative tests. At best, then, there were no treatment failures, and at worst 1 failure. Table I. Follow-up of patients after treatment with mezlocillin
No. patients
FOIIOW-UP (days) 1 to8
24 to 35
46 29 20 13
42 to 60
13
9 to 13 14 to 21
101
No. patients with gonococcus isolated
2
5 ~~~~
Assessment
Cured Cured 2 re-infections Cured: 3 patients developed postgonococcal urethritis Cured: 2 patients developed postgonococcal urethritis Cured
~
Five men developed post-gonococcal urethritis later in the follow-up period. 791
Mezlocillin in gonorrhoea: a pilot study -
Downloaded by [University of California Santa Barbara] at 09:41 06 November 2015
Penicillin sensitivity Gonococci were isolated from 49 of the 50 patients. None were beta-lactamase producers and only one had any marked resistance to penicillin. This patient responded satisfactorily to mezlocillin. Side-efects Immediate. Two patients complained of dizziness during the injection, while another 2 complained of nausea. These effects were transient. One patient vomited bilious fluid within a few seconds of the injection being started. The injection was completed without further upset. Delayed. Occipital headache developed in 1 case a few hours after the injection and persisted for 6 hours. Another developed diarrhoea 24 hours after the injection. It is not known, however, if these symptoms were related to the mezlocillin injection.
Comment The results of this pilot study suggest that mezlocilliii is effective and well tolerated and worthy of an extended trial in the treatment of uncomplicated gonorrhoea.
Acknowledgements We should like to thank the Microbiology Department, Birmingham General Hospital, and Dr. J . Mason, Bayer U.K., for help and advice in this study.
References I . Ashford, W. A,, Golash, R. G . . and Hemming, V. G., (1976). Penicillinase-producing Neisseria gonorrhoeae. Lancet, 2, 657. 2. Bywater, M. J., Holt, H. A , , Broughall, J. M., and Reeves, D. S., (1978). Azlocillin, mezlocillin, pivmecillinam, mecillinam and PC-904: laboratory study of azlocillin and mezlocillin including comparison with other agents. In: “Current Chemotherapy”, Vol. 1, pp. 624-631. Proc. Xth Int. Congr. Chemotherapy, Zurich. American Society for Microbiology, Bethesda, Ma. 3. Gray, R. C. F., Phillips, I., and Nicol, C. S., (1970). Treatment of gonorrhoea with three different antibiotic regimes: doxycycline 300 mg, procaine penicillin plus benzyl penicillin 2.4 mu, benzyl penicillin 5 mu plus probenecid. Br. f. Vener. Dis., 46,401. 4. Phillips, I., (1976). p-lactamase-producing, penicillin resistant gonococcus. Lancer, 2,656. 5 . Wise, R., Gillett, A. P., Andrews, J. M., and Bedford, K. A., (1978). Activity of azlocillin and rnezlocillin against Gram-negative organisms: comparison with other penicillins. Antimicrob. Agents Chemofher..,13, 559.
792
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: http://www.tandfonline.com/loi/icmo20
Mezlocillin in gonorrhoea: a pilot study W. Fowler & M. H. Khan To cite this article: W. Fowler & M. H. Khan (1979) Mezlocillin in gonorrhoea: a pilot study, Current Medical Research and Opinion, 5:10, 790-792, DOI: 10.1185/03007997909109015 To link to this article: http://dx.doi.org/10.1185/03007997909109015
Published online: 11 Aug 2008.
Submit your article to this journal
Article views: 2
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icmo20 Download by: [University of California Santa Barbara]
Date: 06 November 2015, At: 09:41
Downloaded by [University of California Santa Barbara] at 09:41 06 November 2015
Current Medical Research and Opinion
Vol. 5, No. 10, 1979
Mezlocillin in gonorrhoea: a pilot study
and
W. Fowler, M.D.,
M. H. Khan, M.B.,B.S. Department of Venereal Disease, General Hospital, Birmingham, England
Cum. Med. Res. Opin., (1979), 5,790.
Received : 12th December 1978
Summary A pilot study was carried out in 50 patients with uncomplicated, untreated gonorrhoea to assess the effectiveness of mezlocillin, a new semi-synthetic penicillin. Patients received a single intravenous injection of 2 g mezlocillin and werefollowed-up for periods up to I01 days. Four patients defaulted immediately. Clinical and bacteriologicalfindings showed that only I of the 46patients followed-up had failed to respond to treatment, indicating a cure rate of97.8 %. Five (10.8 %) male patients haddeveloped post-gonococcal urethritis when seen 3 weelcs or later in the follow-up period.
Key words: Mezlocillin - penicillins - gonorrhoea
Introduction The unexpected appearance of beta-lactamase-producing strains of gonococci1. 4 completely resistant to penicillin has tended, for the moment, to obscure the longterm threat to the value of penicillin in gonorrhoea posed by the continuing tendency of non-enzyme-producing strains of gonococci to become increasingly insensitive to this antibiotic. Already, such large increases in the amount of penicillin (5 mu. benzyl penicillin), often with the addition of probenecid,3 have been necessary in some areas to maintain the efficacy of penicillin that it would seem likely that the limit had been reached so far as ‘one shot’ therapy is concerned. This has led to a pilot study of mezlocillin,2.5 a new semi-synthetic penicillin, which has an in vitro spectrum encompassing those of carbenicillin and ampicillin but is much more active against Pseudomonas aeruginosa, Klebsiella, E. coli and Proteus, and exceptionally active against the gonococcus.
Patients and methods Fifty patients (46 male, 4 female) suffering from uncomplicated, untreated gonorrhoea were included in this pilot study. The 4 females were on oral contraceptives. None of the patients were allergic to penicillin or were undergoing treatment for any other condition. Age, marital status, and racial incidence presented no unusual features. The diagnosis was made on the presence of Gram-negative diplococci morphologically identical to gonococcus in films and/or gonococci grown on modified 790
Downloaded by [University of California Santa Barbara] at 09:41 06 November 2015
W. Fowler and M. H . Khan
Thayer-Martin medium. Films and cultures were taken from the urethra in males and from the urethra and cervix in females. In the latter, cultures were also taken from the pharynx and rectum. Sensitivity to penicillin was determined by the disc diffusion method. Any strains showing undue resistance were tested for betalactamase production by the chromogenic cephalosporin 87/312. The fact that this was a pilot study was explained to the patient and consent obtained in writing before the treatment was given. This consisted of 2 g mezlocillin dispersed in 20 ml sterile water slowly injected (1; minutes) into an antecubital vein. Patients were advised t o abstain from sexual intercourse and alcohol for at least 14 days, to attend on the 3 successive days following treatment and then at weekly intervals for 2 weeks, then after 1 month and 2 months. In females, it was proposed t o take films and cultures from the urethra and cervix at each follow-up visit and also from the pharynx and rectum if these sites had been positive initially. In males, the aim was to make films and cultures from any urethral discharge or from urethral scrapings if there was no apparent discharge at the 3 daily visits or within the first 2 weeks but, subsequently, not to take films and cultures unless there were symptoms or clinical evidence (including the state of the urine) to suggest that urethritis was present.
Results The 4 females fulfilled the follow-up schedule. All were cured. Four male patients defaulted immediately and only 9 attended for 3 successive days after treatment. In each case the urethral discharge was still profusely purulent on the day after treatment but had diminished markedly by the third day. Gonococci were not isolated in any of these cases. Details of the full follow-up are shown in the Table I. It will be noted that gonococci were isolated in 2 male cases 14 to 21 days after treatment. I n 1 case there was a history of reinfection. This was denied in the other case but was open to doubt in view of the two previous negative tests. At best, then, there were no treatment failures, and at worst 1 failure. Table I. Follow-up of patients after treatment with mezlocillin
No. patients
FOIIOW-UP (days) 1 to8
24 to 35
46 29 20 13
42 to 60
13
9 to 13 14 to 21
101
No. patients with gonococcus isolated
2
5 ~~~~
Assessment
Cured Cured 2 re-infections Cured: 3 patients developed postgonococcal urethritis Cured: 2 patients developed postgonococcal urethritis Cured
~
Five men developed post-gonococcal urethritis later in the follow-up period. 791
Mezlocillin in gonorrhoea: a pilot study -
Downloaded by [University of California Santa Barbara] at 09:41 06 November 2015
Penicillin sensitivity Gonococci were isolated from 49 of the 50 patients. None were beta-lactamase producers and only one had any marked resistance to penicillin. This patient responded satisfactorily to mezlocillin. Side-efects Immediate. Two patients complained of dizziness during the injection, while another 2 complained of nausea. These effects were transient. One patient vomited bilious fluid within a few seconds of the injection being started. The injection was completed without further upset. Delayed. Occipital headache developed in 1 case a few hours after the injection and persisted for 6 hours. Another developed diarrhoea 24 hours after the injection. It is not known, however, if these symptoms were related to the mezlocillin injection.
Comment The results of this pilot study suggest that mezlocilliii is effective and well tolerated and worthy of an extended trial in the treatment of uncomplicated gonorrhoea.
Acknowledgements We should like to thank the Microbiology Department, Birmingham General Hospital, and Dr. J . Mason, Bayer U.K., for help and advice in this study.
References I . Ashford, W. A,, Golash, R. G . . and Hemming, V. G., (1976). Penicillinase-producing Neisseria gonorrhoeae. Lancet, 2, 657. 2. Bywater, M. J., Holt, H. A , , Broughall, J. M., and Reeves, D. S., (1978). Azlocillin, mezlocillin, pivmecillinam, mecillinam and PC-904: laboratory study of azlocillin and mezlocillin including comparison with other agents. In: “Current Chemotherapy”, Vol. 1, pp. 624-631. Proc. Xth Int. Congr. Chemotherapy, Zurich. American Society for Microbiology, Bethesda, Ma. 3. Gray, R. C. F., Phillips, I., and Nicol, C. S., (1970). Treatment of gonorrhoea with three different antibiotic regimes: doxycycline 300 mg, procaine penicillin plus benzyl penicillin 2.4 mu, benzyl penicillin 5 mu plus probenecid. Br. f. Vener. Dis., 46,401. 4. Phillips, I., (1976). p-lactamase-producing, penicillin resistant gonococcus. Lancer, 2,656. 5 . Wise, R., Gillett, A. P., Andrews, J. M., and Bedford, K. A., (1978). Activity of azlocillin and rnezlocillin against Gram-negative organisms: comparison with other penicillins. Antimicrob. Agents Chemofher..,13, 559.
792
