Reduced susceptibility to first-line drug causes change in UK gonorrhoea prescribing practice

UK Prescribing guidance for the treatment of gonorrhoea needs to change because of increasing prevalence of bacteria with reduced susceptibility to the first-line antibiotic cefixime, the Health Protection Agency (HPA) has announced. 

Some 17% of gonorrhoea samples tested in 2010 had reduced susceptibility to cefixime, an increase of  6% since 2009. Gay men were especially likely to be infected with strains of the bacteria with reduced susceptibility to the drug, as were patients with HIV and those reporting larger number of sexual partners.

Professor Cathy Ison of the HPA commented: “Our lab tests have shown a dramatic reduction in the sensitivity of the drug we were using as the main treatment for gonorrhoea.”

Fears of resistance prompted a change in UK gonorrhoea treatment guidelines in May 2011. Recommended therapy now consists of ceftriaxone  500 mg (via injection) combined with  an oral dose of azithromycin (1 g) as first-line treatment, with cefixime and azithromycin  as second-line  treatment for patients who refuse the injection.

“This won’t solve the problem,” said Professor Ison, “history tells us that resistance to this therapy will develop too. In the absence of any new alternative treatments for when this happens, we will face a situation where gonorrhoea cannot be cured.”

Use of penicillin, tetracycline, and ciprofloxacin as first-line gonorrhoea therapy was previously abandoned because of resistance, and guidance recommending cefixime and ceftriaxone was issued as recently as 2004. Cefixime belongs to a class of antibiotics known as third generation cephalosporins.

Drug-resistant gonorrhoea is a global problem. World Health Organization guidelines recommend that first-line therapy for the infection should be changed when treatment failure rates reach 5%. The UK move away from cefixime is therefore pre-emptive, but indicates the seriousness with which doctors regard the upsurge in bacteria with reduced susceptibility to the drug.

The HPA tested 1425 gonorrhoea samples collected at 26 sexual health clinics between July and September 2010.

Overall, 17% of isolates had reduced susceptibility to a a 0.125 mg/l concentration of cefixime, up from 11% in 2009. Reduced susceptibility was also seen in 6% of samples exposed to a 0.250 mg/l concentration of the drug, an increase of approximately 1% on the previous  year.

The investigators also found that 20% of samples had reduced susceptibility to penicillin, with 69% having reduced susceptibility to tetracycline and 35% to ciprofloxacin. The HPA continues to caution against their use unless tests first show the sensitivity of the bacteria.

In all 10% of samples with resistance to penicillin and ciprofloxacin also had reduced susceptibility to cefixime. However, prevalence of bacteria with resistance to azithromycin, which is now recommended for use with ceftriaxone, stood at only 1%.

Decreased antibiotic sensitivity was more common in patients reporting two or more sexual partners in the previous three months. Moreover, patients who were infected at multiple sites (p < 0.001), had concurrent chlamydial infection (p < 0.001) and were HIV positive (p < 0.001) were more likely to have gonorrhoea with reduced susceptibility to the 0.125 mg/l concentration of cefixime.

A quarter of samples collected from gay men had reduced susceptibility to cefixime, compared to just 4% of isolates obtained from heterosexual men and 2% of samples from heterosexual women.

“The continued trend towards gonococci exhibiting decreased susceptibility to third generation cephalosporins presents the very real threat of untreatable gonorrhoea in the future,” comment the HPA.  “In the absence of any new treatment options, a coordinated response to this new challenge from clinicians, microbiologists and epidemiologists will be necessary and may require considerable change to current practices."

They continue: “Clinicians need to be aware of the importance of prescribing the  recommended therapy, ceftriaxone, rather than cefixime and be vigilant for possible treatment failure. Test of cure may become increasingly necessary, not just for individual patient management but also as a public health measure to prevent onward transmission and dissemination of resistant strains.”