Ciprofloxacin resistant gonorrhoea in England and Wales - a
changing epidemiology?
The prevalence of resistance to ciprofloxacin in
Neisseria
gonorrhoeae in England and Wales has stabilised after a rapid increase
observed in 2002 [1], according to results from the 2003 collection of the
Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) [2]
.
Between June and August 2003, gonococcal isolates from patients at 26 genitourinary
medicine (GUM) clinics in England and Wales were tested for antimicrobial
susceptibility at one of two central reference laboratories. The minimum
inhibitory concentrations (MICs) of five antimicrobials were determined,
including ciprofloxacin (range tested 0.002-0.125 mg/l, extended to 32 mg/l
as necessary). Clinical, demographic, and behavioural data were obtained
for each patient included in the collection.
Over 1900 isolates from GUM clinics were tested during this time period
in 2003. The overall prevalence of ciprofloxacin resistance (MIC ≥1
mg/l) was 9.0% in 2003 compared to 9.8% in 2002, but this decrease was not
statistically different (p=0.57). A decrease in prevalence was observed
in sentinel clinics outside London during this period, from 12.4% to 9.9%.
However, London saw a slight increase in ciprofloxacin resistance from the
7.2% to 7.9% in 2003. In 2003 the prevalences of ciprofloxacin resistance
remained at ≥5% in all regions of England and Wales. A more homogenous distribution
in the prevalence of ciprofloxacin resistance across the regions was seen
in 2003 compared with previous years, with the exception of the West Midlands
region where a high prevalence of 21%, more than double the prevalence seen
in any other region, was observed.
The distribution of ciprofloxacin resistance within the population appears
to be changing. In 2003 ciprofloxacin resistance was again about twice as
high in all males than in females (10.4% versus 5.3%, p<0.0005). For
the first time, however, similar percentages of ciprofloxacin resistance
were observed in both heterosexual males and men who have sex with men (MSM)
(10.8% and 10.7% respectively). These findings suggest ciprofloxacin resistance
has become widely distributed and endemic within the population. In 2000,
ciprofloxacin resistance in England and Wales was almost exclusively found
in white and Asian (here defined as South Asian and Chinese) ethnic groups
and heterosexual individuals.
Multivariate analysis in 2003 indicates ciprofloxacin resistance continues
to be higher in individuals of white ethnicity (compared with black ethnic
groups, here defined as African and African-Caribbean). It also continues
to be higher in the relatively small groups of patients aged >45yrs (24%
resistant), in those from the Asian ethnic group (23% resistant), and in
those who had had sexual contact in the Far East in the previous 3 months
(67% resistant).
When the significant increase in the prevalence of ciprofloxacin resistance
to 9.8% was observed in England and Wales in 2002, alternative first-line
therapies to ciprofloxacin or penicillin were recommended by the GRASP steering
group [2]. Subsequently, the Clinical Effectiveness Group (British Association
of Sexual Health and HIV) gonococcal treatment guidelines were reviewed
in response to these recommendations. These guidelines recommend the use
of the third generation cephalosporins ceftriaxone and cefixime in place
of fluoroquinolones or penicillin as first line therapies [3]. They also
highlight the need for region-specific prescribing strategies depending
on the local antimicrobial resistance prevalence and distribution.
Reports of increases in the prevalence of ciprofloxacin resistance in N.
gonorrhoeae have been observed over recent years in several other European
countries. Scotland has seen ciprofloxacin resistance rise to 11% in 2002
[4], and Spain has seen a rapid increase from 2.3% to 9.9% between 2000
and 2001 [5]. Furthermore, a recent report from Sweden highlighted a dramatic
increase in the prevalence of ciprofloxacin resistant gonorrhoea reported
in Stockholm and other parts of Sweden during 2003. Ciprofloxacin resistant
cases in men attending a clinic for homosexual men in Stockholm increased
from a low level to over 50% during 2003. An outbreak of ciprofloxacin resistant
gonorrhoea was also identified amongst heterosexual men and women in the
county of Galveborg [6].
The findings discussed here demonstrate the importance of maintaining ongoing
surveillance of gonococcal antimicrobial resistance at a national level
to ensure treatment strategies remain responsive to the changing epidemiology.