International http://std.sagepub.com/ Journal of STD & AIDS

Comparative Study of Cefuroxime Axetil and Procaine Penicillin in the Treatment of Uncomplicated Gonorrhoea G R Kinghorn, R C Spencer, T K Smith, P D Woolley, R Patel and A J Robinson Int J STD AIDS 1990 1: 285 DOI: 10.1177/095646249000100412 The online version of this article can be found at: http://std.sagepub.com/content/1/4/285

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International Journal of STD & AIDS 1990; 1: 285-287

ORIGINAL ARTICLE

Comparative study of cefuroxime axetil and procaine penicillin in the treatment of uncomplicated gonorrhoea G R Kinghorn MD FRCp1, R C Spencer MB FRCPath2, T K Smith FIMLS2, PO Woolley DRCOG MRCPl, R Patel MB MRCP 1 and A J Robinson MB MRCp1 IDepartment of Genitourinary Medicine and 2Department of Bacteriology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2IF, UK Summary: A total of 311 patients presenting with uncomplicated gonorrhoea were entered into a comparative randomized open-label study and given single-dose treatment with either oral cefuroxime axetil (CAE) or intramuscular procaine penicillin (PP). Neisseria gonorrhoeae was eliminated from 129 (98%) of 131 evaluable patients treated with CAE and 127 (98%) of 129 evaluable patients treated with PP. None of the 4 treatment failures (3 male and 1 female) were caused by p-Iactamaseproducing isolates. Both treatments were well tolerated with minor adverse events reported in 3 (2%) of CAE treated patients. . . We conclude that CAE is an effective, well tolerated treatment for uncomplicated gonorrhoea which has the convenience and acceptability of single-dose oral therapy. Keywords: Cefuroxime axetil, procaine penicillin, gonorrhoea

strated microscopically or who were culturepositive. Samples were taken from the urethra of heterosexual men and from the urethra, rectum and pharynx of homosexual men. Women who were known contacts had specimens routinely taken from the urethra, cervix, rectum and pharynx: other women found positive in routine cultures from the urethra and cervix also had additional samples taken from the rectum and pharynx at follow-up examinations. All patients gave informed consent to enter the study. Patients were randomized sequentially, using hidden entry envelopes, to receive either CAE 1 g orally or PP 2.4 Mu intramuscularly given in 2 injections. Follow-up examinations were performed 2-15 days following treatment. To be eligible for the analysis, patients had to receive treatment within 4 days of the date of their positive cultures and re-attend for follow-up examination and repeat microbiological examination PATIENTS AND METHODS between 2 and 15 days after treatment. Patients who had taken any other antimicrobial, with the Study population exception of metronidazole or clotrimazole, during We studied a total of 311 consecutive patients the interim period were also excluded. presenting with a clinical diagnosis of uncomplicated gonorrhoea in whom N. gonorrhoeae was demonBacteriological methods

INTRODUCTION Intramuscular cefuroxime is acknowledged to be an effective treatment for uncomplicated gonorrhoea, inclUding infection by p-Iactamase-producing strainsl,2. Cefuroxime axetil (CAE) is an orallyabsorbed ester of cefuroxime which provides the convenience of oral therapy. Preliminary studies in North America and Europe using a 1 g single dose with or without probenecid have produced cure rates of 98-100%, similar to that seen for amoxycillin plus probenecidv". . For 20 years, aqueous procaine penicillin (PP) Intramuscularly has been our first choice treatment of uncomplicated gonorrhoea. We investigated .the bacteriological efficacy and tolerance of cefuro~e axetil against our standard therapy in a randomized trial.

Correspondence to: Dr G R Kinghorn, Department of GenitOUrinary Medicine, Royal Hallamshire Hospital, Glossop Road, Sheffield 510 2]F, UK

All samples were inoculated immediately on to gonococcal medium, composed of Difco GC agar base, 10% lysed horse blood, 1% sterile defined

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International Journal of SID & AIDS Volume 1 July 1990

supplement (Kellogg's modified formula), and Oxoid antibiotic supplement, and were incubated in an atmosphere containing 8% carbon dioxide. N. gonorrhoeae was identified by carbohydrate utilization and the production of i3-lactamase was tested using the chromogenic cephalosporin technique (quad FERM, API Laboratory Products Ltd). Agar dilution susceptibility testing was performed for cefuroxime and penicillin using an inoculum of 5 x lOS colony-forming unitstml on the gonococcal medium without the antibiotic supplement. The minimum inhibitory concentration (MIC) was the lowest concentration of antibiotic which inhibited the growth of the organism after incubation for 24h. RESULTS

A total of 174 men and 137 women were enrolled into the study. Their sites of infection are shown in Table 1. There were 51 patients who were deemed to have unevaluable results-17 in whom follow-up was later than 15 days after treatment, 10 for complete default from follow-up, 11 in whom treatment was given more than 4 days after their initial positive cultures, 9 for negative pre-treatment cultures and 2 each for early follow-up and the use of concurrent antibiotics. Table 2 shows the bacteriological response of patients to treatment. Amongst male patients, 77 of 78 (99%) were successfully treated with CAE compared with 72 of 74 (97%) successfully treated with PP. Amongst female patients, 52 of 53 (98%) were cured by CAE compared with all 55 (100%) who were successfully treated with PP. Table 1. Distribution of sites infected with Neisseria

gonorrhoeae Site Treatment group CAE Male (n=87) Female (n=70) PP Male (n=87) Female (n=67)

Urethra Cervix

Rectum

Table 2. Bacteriological response to treatment No. of patients cured/No. evaluated (%) Treatment group

Male

Female

Total

CAE PP

77/78 (98.7) 72/74 (97.3)

52/53 (98.1) 55/55 (100)

129/131 (98.5) 127/129 (98.4)

i3-Lactamase-producingstrains were isolated from none of the evaluable patients. Two other patients, unevaluable because the timing of follow-up cultures did not comply with the study protocol, had i3-lactamase-producing isolates. A man treated with CAE was culture-negative 40 days posttreatment whilst the other man treated with PP remained culture-positive the day after treatment. The results of antimicrobial sensitivity studies are shown in Table 3. All clinical isolates tested were susceptible to cefuroxime concentrations of ~ 4 mgtl. Both i3-lactamase-producing strains were resistant to > 8 mgtl penicillin: The isolate from the male patient who apparently failed to respond to CAE had a cefuroxime MIC of 0.01 mgtl; reinfection was considered likely, as he had been re-exposed to an untreated partner prior to follow-up. The sole woman who failed to respond to CAE had the organism successfully eradicated from the urethra and cervix but it had persisted in the pharynx. The MIC of cefuroxime was 0.03 mgtl for this isolate. Adverse events after treatment were rarely reported by patients in either treatment group. Three patients treated with CAE reported adverse events, one each with vomiting, diarrhoea and skin erythema. Although minor discomfort associated with the injection procedure was commonly reported by patients treated with PP, no subsequent adverse events were reported in this treatment group.

Pharynx

DISCUSSION 87 41

60

13

5

83 49

60

21

1 7

Although i3-lactamase-producing N. gonorrhoeae are uncommon in the UK, where their level has stabilized at around 5-6%7, they remain very common in developing countries. In Sheffield, where antibiotic-resistant gonococci are rare, and

Table 3. Number (%) of clinical isolates inhibited by different concentrations of cefuroxime and penicillin MIC (mg/l) Antibiotic

liOO.01 0.02

0.03

0.06

0.08

0.13

0.25

0.5

1

2

4

Cefuroxime (271 isolates)

No. %

61 23

139 51

190 70

240e 89

240 89

260 96

266 98

268 99

270 99

270 99

271 100

Penicillin (286 isolates)

No. %

45 16

110 38

152 53

178 62

183 64

240 84

269 94

278 97

281 98

283 99

284 99

Data from 286 patients (no results available for 25 patients) e2 PPNG isolates

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~8

286100

Kinghorn et ai. Cefuroxime axetil, procaine penicillin and gonorrhoea

virtually always'imported', there has until recently been less pressure to consider alternatives to PP for the treatment of gonorrhoea. Nevertheless, the increasing unavailability and rising cost of this preparation, coupled with the decreasing patient acceptability of injectable treatments necessitated that we investigate an effective orally-active alternative. We found that both CAE and PP were equally effective treatments, were well tolerated, and safe for patients of both sexes presenting with uncomplicated anogenital gonorrhoea. CAE had the advantages of ease of administration and high patient acceptability; our experience of its use against fj-lactamase-producing strains was limited. Our results are similar to those of Baddour et al.6 who found CAE to be as effective as amoxycillin with probenecid in a study of 466 female patients. In this study, single dose CAE cleared only 60% of pharyngeal infections; it is interesting that of the only 2 treatment failures with CAE that one was a pharyngeal infection. Four other pharyngeal infections were successfully treated. Adverse events considered related to treatment were uncommon. We conclude that CAE is a safe, effective and convenient treatment for uncomplicated gonorrhoea in either sex. Further experience of its efficacy in treating l3-lactamase-producing gonococci is desirable.

287

Acknowledgements: We wish to acknowledge with thanks the support given by Glaxo and the invaluable contribution made by Doctors Helen Watts and Elaine Anderson.

References 1 Lossick JG, Thompson SE, Smeltzer MP. Comparison of cefuroxime and penicillin in the treatment of uncomplicated gonorrhoea. Antimicrob Agents Chemother 1982;22:409-13 2 Stolz E, Ong L, Van Joost Th, Michel MF. Treatment of noncomplicated urogenital, rectal and oropharyngeal gonorrhoea with intramuscular cefotaxime 1.0 g or cefuroxime 1.5 g J Antimicrob Agents Chemother 1984;14(Suppl B):295-9 3 Oas RP, Jones K, Robinson AJ, Timmins OJ. Cefuroxime axetil to treat gonorrhoea. Genitourin Med 1988;64:394 4 Fong IW, Linton W, Simbul M, Hinton NA. Comparative clinical efficacy of single oral doses of cefuroxime axetil and amoxicillinin uncomplicated gonococcalinfections. Antimicrob Agents Chemother 1986;30:321-2 5 Wanas TM, Williams PEO (1986). Oral cefuroxime axetil compared with oral ampicillinin treating acute uncomplicated gonorrhoea. Genitourin Med 1986;62:221-3 6 Baddour LM, Gibbs RS, Mertz G, Cocchetto OM, Noble RC. Clinical comparison of single oral dose cefuroxime axetil and amoxicillin with probenecid for uncomplicated gonococcal infections in women. Antimicrob Agents Chemother 1989;33:801-4 7 Goh BT, Rodin P, Johnston NA, Wong HH. Penicillinaseproducing Neisseria gonorrhoeae epidemiology, antimicrobial susceptibility and plasmid types. J Infect 1985;11:63-9

(Accepted 24 April 1990)

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