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| Journal of the New Zealand Medical Association,
02-April-2004, Vol 117 No 1191
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Antimicrobial susceptibility among
Neisseria gonorrhoeae in New Zealand in
2002
Helen Heffernan, Mike Brokenshire, Rosemary Woodhouse, Anne
MacCarthy, and Tim Blackmore
After chlamydia, gonorrhoea is the second-most common
bacterial sexually transmitted infection among attendees at sexual health
clinics in New Zealand. The number of cases of gonorrhoea diagnosed at sexual
health clinics has increased each year since 1996, with an overall increase of
94% between 1996 and
2002.1
In recent years, the incidence of gonorrhoea has also increased in other
developed countries, with the highest rates in certain socially and economically
deprived subpopulations, and in men who have sex with
men.2–5
Increasing antimicrobial resistance, especially to
penicillin and the fluoroquinolones, is compromising the effective treatment of
gonorrhoea. Since penicillin resistance emerged in the late 1970s, it has spread
to most parts of the world. Ciprofloxacin resistance first emerged (and then
become particularly common) in South East Asia and the Western
Pacific.6,7 Based on data available from
LabPlus, Auckland District Health Board, there was a large increase in
ciprofloxacin resistance in the Auckland region during 2001, with a four-fold
rise in resistance that year to a rate of
10.1%.7,8
This survey was undertaken to estimate the prevalence of
antimicrobial resistance among Neisseria
gonorrhoeae in New Zealand and to determine whether the increase in
ciprofloxacin resistance observed in the Auckland region in 2001 had occurred in
other parts of the country. Data on the national and regional incidence of
culture-positive gonorrhoea, and the age/sex distribution of patients, are also
presented in the results.
MethodsCommunity and hospital
laboratories throughout New Zealand were requested to refer all
N. gonorrhoeae isolated between 17
April and 16 August 2002 to either LabPlus or the Institute of Environmental
Science and Research (ESR). The data collected with each isolate included
patient date of birth or age, sex, anatomical site, and place (New Zealand
versus an overseas country) where the infection was acquired. Repeat isolates
were excluded. Ceftriaxone, ciprofloxacin, penicillin, spectinomycin, and
tetracycline minimum inhibitory concentrations (MICs) were determined by agar
dilution using the method of the Australian Gonococcal Surveillance
Programme.9
MICs were interpreted as follows: ceftriaxone MIC ≤0.03 mg/L =
susceptible (S), MIC 0.06-0.25 mg/L = reduced susceptibility or less susceptible
(I); ciprofloxacin MIC ≤0.03 mg/L = S, MIC 0.06-0.5 mg/L = I, MIC ≥1
mg/L = resistant (R); penicillin MIC ≤0.03 mg/L = S, MIC 0.06-0.5 mg/L =
I, MIC ≥1 mg/L = R; spectinomycin MIC ≤64 mg/L = S, MIC ≥128
mg/L = R; and tetracycline MIC ≤0.5 mg/L = S, MIC ≥1 mg/L = R.
Beta-lactamase production was determined with the chromogenic cephalosporin,
nitrocefin (Glaxo, Greenford, England).
Isolates were identified as originating from the health
district in which the referring laboratory was located. For the geographic
distribution analysis, health districts were aggregated as follows: the
Northland/Auckland region included Northland, North West Auckland, Central
Auckland and South Auckland Health Districts; the Waikato region included
Waikato Health District; the Bay of Plenty region included Tauranga, Eastern Bay
of Plenty and Rotorua Health Districts; the Gisborne/Hawkes Bay region included
Gisborne and Hawkes Bay Health Districts; the Taranaki/Wanganui/Manawatu region
included Taranaki, Wanganui and Manawatu Health Districts; the Wellington region
included Wairarapa, Hutt and Wellington Health Districts; and the South Island
region included all health districts in the South Island. Annualised incidence
rates were based on 2001 census population.
ResultsA total of 413
N. gonorrhoeae isolates from 26
laboratories were included in the survey. As the survey aimed to include all
N. gonorrhoeae isolated during a
4-month period in New Zealand, this number of isolates equates to an annualised
national incidence of culture-positive gonorrhoea of 33.2 cases per 100 000
population. Both age and sex were reported for 400 (96.9%) of the 413 patients.
The age and sex distribution of these patients is shown in Figure 1.
 Figure 1. Age
and sex distribution of patients from whom
Neisseria gonorrhoeae were
isolated
Antimicrobial
susceptibility The MIC range, MIC50,
MIC90, and prevalence of reduced susceptibility
and resistance to each antimicrobial among the 413 isolates tested is shown in
Table 1. Penicillin resistance may be due to either plasmid-mediated production
of beta-lactamase (penicillinase-producing N.
gonorrhoeae, PPNG) or chromosomally mediated mechanisms (CMRNG). Among
the 9.0% of isolates that were penicillin resistant, 3.9% were PPNGs and 5.1%
were CMRNG. Tetracycline resistance may also be either plasmid or chromosomally
mediated. Among the 27.8% of isolates that were tetracycline resistant, 6.5% had
high-level, plasmid-mediated resistance (MIC ≥16 mg/L) and 21.3% had
low-level, chromosomally mediated resistance (MIC 1-8 mg/L).
Table 1. MIC range,
MIC50, MIC90, and
resistance among Neisseria gonorrhoeae,
2002
*There is no reduced susceptibility/less susceptible
category for spectinomycin or tetracycline.
Over a quarter (28.6%) of the isolates were resistant to at
least one of the antimicrobials tested, with 6.3% of the isolates resistant to
both ciprofloxacin and tetracycline, and 8.5% resistant to both penicillin and
tetracycline.
Geographic differences in
ciprofloxacin and penicillin resistance The prevalence of ciprofloxacin
and penicillin resistance by region, based on the location of the referring
laboratory, is shown in Table 2. Because some laboratories process specimens
from patients who live outside the area in which the laboratory is located, this
geographic analysis may not strictly reflect the patients’ place of
residence. The only significant geographical differences in ciprofloxacin and
penicillin resistance were lower rates of resistance in the Gisborne/Hawkes Bay
region than in the Northland/Auckland region.
Differences in
ciprofloxacin and penicillin resistance among New Zealand-acquired infections
compared with infections acquired overseas The country or overseas region
where the infection was acquired was reported for 185 (44.8%) of the 413
patients. Only 13.0% of these 185 patients were reported to have acquired their
infection overseas. Compared with infections acquired in New Zealand, infections
acquired in Asia were more likely to be ciprofloxacin resistant [57.1% (95% CI
28.9-82.3%) vs 6.8% (95% CI 3.5-11.9%)] and penicillin resistant [85.7% (95% CI
57.2-98.2%) vs 6.8% (95% CI 3.5-11.9%)].
Table 2.
Geographical differences in the incidence of culture-positive gonorrhoea
and ciprofloxacin and penicillin resistance, 2002
Wang* = Wanganui; Mana* = Manawatu
DiscussionCiprofloxacin has become the most
widely used treatment for gonorrhoea in New Zealand because of its convenience
and the prevalence of penicillin
resistance.10
However, based on the results of this survey, 6.8% of
N. gonorrhoeae isolated in New Zealand
are now resistant to ciprofloxacin, and a further 5.8% have reduced
susceptibility. These results indicate there is a need to consider alternative
first-line treatment options for gonorrhoea.
The emergence of gonococcal resistance to fluoroquinolone
drugs, such as ciprofloxacin, was first observed in South East Asia and the
Western Pacific in the early 1990s. By 2001, there were extraordinarily high
rates of fluoroquinolone resistance in many countries in these regions. For
example, 88% resistance in Hong Kong, 87% in China, 64% in Japan, 54% in the
Philippines, and 43% in Cambodia.7
In most developed countries, ciprofloxacin resistance was
first associated with imported infections acquired in South East Asia and the
Western Pacific, but there is now an endemic focus of ciprofloxacin-resistant
strains in some of these countries—including
Australia,11
California and Hawaii in the United
States,12 and the United
Kingdom.13
This pattern of importation, followed by local spread, is also evident in
New Zealand. DNA macrorestriction typing, auxotyping, and serotyping of a
selection of ciprofloxacin-resistant isolates from Auckland at the beginning of
2001 showed that the majority belonged to one
strain.14
This finding is consistent with local spread rather than ongoing
importation of strains.
During the 14 years since the last national survey in
1988,15
penicillin resistance has increased nearly four-fold—from 2.5% in
1988 to 9.0% in 2002. Most of the increase has been due to CMRNG, rather than
PPNG. Concomitant with the increase in CMRNG, the prevalence of strains with
reduced penicillin susceptibility also increased markedly—from 47.7% in
1988 to 68.5% in 2002. While strains with reduced susceptibility can usually be
effectively treated with higher doses of penicillin, they have the potential to
accumulate further mutations, and become fully resistant and untreatable with
penicillin.16
Despite these increases, the prevalence of penicillin
resistance in New Zealand is still relatively low compared with other countries
in South East Asia and the Western Pacific, including
Australia.7 In 2001, rates of penicillin
resistance as high as 96% were reported in Laos, 88% in Korea, and 86% in the
Philippines, with 23% in Australia. Given the high rates of gonococcal
ciprofloxacin and penicillin resistance in many Asian countries, it was not
surprising that infections acquired in Asia were more likely to be ciprofloxacin
and penicillin resistant than those acquired in New Zealand.
Ideally, to guide empirical treatment, the susceptibility of
all N. gonorrhoeae isolated in New
Zealand should be tested using a standardised method either in the primary
laboratory or a reference laboratory. Current antimicrobial susceptibility data
are essential to the control of gonorrhoea, as treatment is usually prescribed
before laboratory testing has been performed. Moreover, patients often do not
attend follow-up appointments. Failure to effectively treat a case of gonorrhoea
has public health implications beyond the failure to cure the patient being
treated. It increases the chances of further spread of the disease, and, in
particular, the spread of resistant strains.
As a general principle, the chosen treatment for gonorrhoea
should cure at least 95% of infections. Therefore, when resistance to an
antibiotic reaches 5%, it is usually considered to no longer be an acceptable
first-line treatment
option.17
Based on the results of this survey, the prevalence of both penicillin
resistance (9.0%) and ciprofloxacin resistance (6.8%) in New Zealand are above
this 5% threshold. In addition, more than 5% of isolates would be resistant to
the commonly used empiric combinations of ciprofloxacin and tetracycline, or
amoxicillin and tetracycline. However, resistance varied throughout New Zealand.
Unfortunately, the numbers of isolates from all regions except
Northland/Auckland were insufficient to calculate precise estimates of the
regional prevalence of resistance. In fact, the Northland/Auckland region was
the only region where the lower 95% confidence intervals for ciprofloxacin and
penicillin resistance were greater than the 5% threshold.
The epidemiology of gonococcal infection reflects the fact
that gonorrhoea is only transmitted by intimate human-to-human contact.
Controlling resistance will therefore be best achieved by effective treatment of
cases and tracing of sexual contacts. The results of this survey suggest that
there is a need to review the treatment of gonorrhoea in New Zealand and
consider new first-line treatment options. Intramuscular or intravenous
ceftriaxone should now be considered the most reliable option for the treatment
and control of gonorrhoea in New Zealand, particularly in the Northland/Auckland
region.
Author information:
Helen Heffernan, Senior Scientist, ESR; Mike Brokenshire, Medical Laboratory
Scientist, LabPlus, Auckland District Health Board; Rosemary Woodhouse, Senior
Technician, ESR; Anne MacCarthy, Medical Laboratory Scientist, LabPlus, Auckland
District Health Board; Tim Blackmore, Clinical Microbiologist, ESR.
Acknowledgements: We
thank the clinical microbiology laboratories throughout New Zealand for
contributing isolates for the survey; Nick Garrett and Michael Eglinton, ESR,
for their assistance with data analysis; and the Ministry of Health for funding
ESR’s contribution to this survey.
Correspondence:
Helen Heffernan, Antibiotic Reference Laboratory, ESR, Box 50 348, Porirua. Fax:
(04) 914 0770; email: helen.heffernan@esr.cri.nz
References:
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