• 
• 

Three Part Question

In [sexually active males having been diagnosed with gonococcal urethritis] is [oral cefixime better than i.m ceftriaxone] at [succesfully eradicating infection]?

Clinical Scenario

A 34-year-old man has been diagnosed with gonococcal urethritis. Your consultant suggests you prescribe oral cefixime, but you had heard that i.m ceftriaxone is the first line treatment for this condition. You wonder which antibiotic would be better at eradicating his infection.

Search Strategy

Medline - 1966 to June week 2 2006
Embase - 1980 to 2006 Week 24
CINAHL - 1982 to June Week 2 2006
The Cochrane Library 2006 Issue 2
Medline/Embase/CINAHL: [exp Urethritis/ OR exp Neisseria gonorrhoeae/ or exp Gonorrhea/ OR gonococcal.mp. OR gonorrhoea.mp.] AND [exp Cefixime/ OR suprax.mp. OR exp Ceftriaxone/ OR rocephin.mp.] limit to humans, English language and male
Cochrane: (Neisseria gonorrhoeae [MESH] OR (gonorrhoea) OR (gonococcal)) AND (cefixime [MESH]) AND (ceftriaxone [MESH])

Search Outcome

Altogether 114 papers were identified using Medline, 249 using Embase and none using CINAHL or Cochrane. Three papers, identified by both Medline and Embase, were relevant to the three part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Portilla et al, Mar-Apr 1992, USA	75 adult male and 150 adult female outpatients with clinical evidence of uncomplicated gonorrhoea attending the Delgado clinic in New Orleans between April 1989 and June 1990	RCT	Gonorrhoea eradication rates in males	95% cefixime 400mg PO v. 91% cefixime 800mg PO v. 100% ceftriaxone 250mg IM	Fairly small sample. Does not give patient demographics for each group and so cannot tell if they are comparable. Study personnel not blinded to treatment. No statistical analysis to see if differences between data are statistically significant.
			Adverse experiences	At least one event reported in 10% of the cefixime group v. none in the ceftriaxone group. All but one of these were women. Most frequently reported event was diarrhoea (3%)
			Gonorrhoea eradication rates according to sites	Urethra = 97.8% cefixime 400mg v. 94.1% ceftriaxone. Rectum = 100% in all drugs. Pharynx = 100% ceftriaxone 250mg (only 1 patient with infection)
Handsfield et al, Nov 1991, USA	333 males and non-pregnant females over 16 years old from several STD clinics across the USA, with uncomplicated gonorrhoea	RCT	Gonorrhoea eradication rates	96% cefixime 400mg PO v. 98% cefixime 800mg PO v. 98% ceftriaxone 250mg IM	Study personnel not blinded to treatment. Numbers with pharyngeal infection very small. No males with rectal infection. Small sample size.
			Adverse events	14.6% overall. Of these 86% mild and 14% moderate. Incidence of adverse effects with 800mg cefixime (18%) was higher than in 400mg (8% p=0.06) or ceftriaxone (4%, p=0.004)
			Antimicrobial susceptibility of N.gonorrhoeae	At least 1 type of resistance in 39%. 26% beta lactamase production, 12% plasmid mediated tretracycline resistance, 12% chromosomally mediated resistance to penicillin or tetracycline
			Gonorrhoea cure rates in different strains	98% cure rate in fully susceptible strains, 96% cured in strains with chromosomally mediated resistance, 96% cured in strains with beta-lactamase and 97% cure rate in strains with plasmid mediated tetracycline resistance
			Gonorrhoea cure rates according to site	Urethra = 97% cefixime 400mg v. 100mg cefixime 800mg v. 100% ceftriaxone 250mg. Pharynx 100% cefixime 400mg v.86% ceftriaxone 250mg
Plourde et al, Oct 1992, Nairobi/Canada	190 patients 18-65 years old attending the Nairobi City Commission Special Treatment Clinic from October 1989-August 1990 with microbial evidence of gonorrhoea	RCT	Gonorrhoea eradication rates in males	98% cefixime v. 100% ceftriaxone	Study personnel not blinded to treatment. States that demographic data was obtained, but is not given so cannot tell if the two groups are comparable. Pre-determinded 2:1 cefixime-to-ceftriaxone ratio used and so cefixime group much larger. Does not state the reasons for this. Small sample size. Does not compare eradication rates for different areas of infection,
			Resistance of N.gonorrhoeae isolates	66% penicillinase production, 29% plasmid mediated tetracycline resistance, 69%/26% chromosomally mediated tetracycline/penicillin resistance
			Adverse events	3.26%. 1.65% cefixime v.6.35% ceftriaxone

Comment(s)

All three studies showed cefixime to be of similar effectiveness to ceftriaxone in eradicated gonococcal urethritis. Portilla et al. and Handsfield et al. also showed that there is no beneficial effect of using 800mg cefixime as opposed to 400mg. Indeed, Handsfield et al. showed the only difference in giving 800mg compared to 400mg was the increased incidence of adverse effects. Cefixime 400mg and ceftriaxone 250mg had similar low rates of adverse effects in all three studies. Sample sizes were too small to determine whether or not the two drugs have a similar efficacy at eradicating gonococcal infection at extra-genital sites. Both drugs have high efficacy against strains of N.gonorrhoeae showing a variety of resistance. The recommendation of all three studies is that oral cefixime 400mg should be the preferred choice against gonococcal urethritis, due to its reduced cost, and the removal of the costs and risks that needles bring. I agree with this recommendation.

Clinical Bottom Line

Cefixime 400mg PO should be the treatment of choice for gonococcal urethritis. Further research is needed to determine its efficacy against extra-genital infection.

References

1. Portilla I, Lutz B, Montalvo M, Mogabgab WJ. Oral cefixime versus intramuscular ceftriaxone in patients with uncomplicated gonococcal infections. Sex Transm Dis. 1992 Mar-Apr;19(2):94-8.
2. Handsfield HH, McCormack WM, Hook EW 3rd et al. A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. The Gonorrhea Treatment Study Group. N Engl J Med. 1991 Nov 7;325(19):1337-41.
3. Plourde PJ, Tyndall M, Agoki E et al. Single-dose cefixime versus single-dose ceftriaxone in the treatment of antimicrobial-resistant Neisseria gonorrhoeae infection. J Infect Dis. 1992 Oct;166(4):919-22.