Abstract

Objectives

To analyse trends in antimicrobial resistance (AMR) in Neisseria gonorrhoeae (GC) isolated in Australia between 1997 and 2006 and to identify factors influencing emergence and spread of AMR in GC.

Methods

AMR data were generated in reference laboratories in each state and territory of Australia using the methods of the Australian Gonococcal Surveillance Programme from a comprehensive sample of GC. Trends in the proportion of strains resistant to penicillin, ciprofloxacin, spectinomycin and ceftriaxone or with high-level tetracycline resistance (TRNG) were determined from aggregated national data and were also disaggregated by region. Further analyses of additional AMR, demographic, transmission and antibiotic use data were also performed.

Results

More than 36 000 GC were examined. Significant increases in resistance to penicillin and ciprofloxacin and in TRNG occurred in national data and in urban populations. Approximately half of the GC tested in larger urban centres were penicillin and/or ciprofloxacin resistant by 2006. These high rates of resistance arose despite low (penicillin) or absent (ciprofloxacin) exposure. In contrast, in rural and remote areas with very high disease rates and high rates of penicillin use, <5% of GC tested were penicillin (or quinolone) resistant. No spectinomycin-resistant GC were detected. Low numbers of GC with raised MICs of ceftriaxone were present in urban centres each year from 2001 onwards.

Conclusions

Significant increases in AMR in GC occurred in parts of Australia in the 10 years to 2006. The data suggest that the AMR seen in GC in urban populations were the result of their repeated importation into Australia and ultimate introduction into established sexual networks rather than originating de novo or as a result of selection by antibiotic use or misuse.

Introduction

Surveillance for antimicrobial resistance (AMR) is used to guide therapy in the individual patient, monitor AMR trends, track the emergence and spread of resistance or to allow advocacy for rational use of antibiotics.1,2 Additionally, in diseases of public health importance such as gonorrhoea, AMR surveillance helps establish and maintain the efficacy of standard treatment regimens to assist in disease control.1–3 Control of gonorrhoea is complex and difficult, requiring an integrated and multidisciplinary approach that includes effective antibiotic treatment.4 This is defined as those single dose regimens, provided at first diagnosis, that result in a cure in 95% or more of cases.4–6 Their formulation thus requires knowledge of AMR patterns in gonococci obtained from surveillance.3–5,7 Programmes for reliable AMR surveillance for Neisseria gonorrhoeae need to accommodate the fastidious gonococcal growth requirements, the propensity of the organism to rapidly acquire resistance and to conform to recognized surveillance standards.1–5

The Australian Gonococcal Surveillance Programme (AGSP) is an established collaborative programme of AMR surveillance conducted in each jurisdiction in Australia.8 It differs from some equivalent programmes9–11 in that it is comprehensive (as opposed to sentinel), continuous (rather than intermittent) and actively integrates AMR analysis with selected clinical data. The origins, procedures and early outcomes of the programme have been published.8,12,13 In addition, the AGSP has provided, in quarterly reports published continuously from 1981 in public health bulletins, timely data on the susceptibility of gonococci to those antibiotics relevant to treatment of gonorrhoea in Australia together with detailed annual analyses from 1996 onwards (available at a dedicated URL).14 Audits of the AGSP indicate that it meets or exceeds World Health Organization and CDC performance criteria for surveillance programmes of this type.15

This report provides further analyses of trends in AMR in gonococci isolated in Australia over the 10 years 1997–2006. Gonorrhoea in Australia has some distinctive features. A largely urban population living mainly in coastal areas has a disease rate and distribution similar to that reported in other Western-style industrialized countries, and with decreasing options for treatment because of increasing AMR. However in non-urban settings in ‘outback’ locations where older treatments, including the penicillins, still remain highly effective, the disease incidence is much higher, although this high rate yields only relatively small numbers of cases due to a low population density. There are also differences in rural and urban disease patterns and some unusual disease manifestations occur.16,17 This paper includes a consideration of these elements to discuss factors influencing the emergence and spread of AMR in gonococci in Australia.

Materials and methods

The structure, function and methods employed by the AGSP have been described previously.8,14,18 Briefly, gonococcal isolates from a comprehensive network of private and public sector laboratories are forwarded to reference centres in each jurisdiction for examination using standardized methodologies. The AGSP determined the MICs of penicillin, ceftriaxone, spectinomycin and ciprofloxacin using agar plate dilution methods with 104 cfu per spot inoculated onto Sensitest agar (Oxoid, Basingstoke, UK) supplemented with 8% saponin-lysed horse blood and appropriate dilutions of the relevant antibiotic (obtained from manufacturers) and incubated in 5% CO2 in air for 24 h. Quality control (QC) strains used in each laboratory, originally WHO A—E, were progressively updated18 through collaboration with other international centres. An external programme-specific quality assurance process (EQAS) was conducted by a co-ordinating centre.19 Comparability of data was obtained by the uniformity of methods and the QC and EQAS programmes. Dilution ranges and resistance criteria were described initially for penicillin8 and with subsequent additions as newer agents were introduced.18 For penicillin (CMRP), ceftriaxone and ciprofloxacin, chromosomally mediated resistance was defined as an MIC ≥ 1 mg/L and decreased susceptibility in the range 0.06–0.5 mg/L. Spectinomycin resistance was defined as an MIC ≥ 64 mg/L and high-level tetracycline resistance (TRNG) as an MIC ≥ 16 mg/L.20 Penicillinase-producing N. gonorrhoeae (PPNG) comprised a separate category of penicillin resistance.

Data from each participating centre were forwarded to the co-ordinating centre for collation, analysis and reporting. Data recorded, as well as the number and proportion of isolates in the resistance categories defined above, included the date and anatomical site of infection, the sex of the patient and post code of residence, and for certain resistant isolates, details of where the infection was acquired.15 A combined analysis of data generated by the AGSP over the period 1 January 1997 to 31 December 2006 provided the basis of this study.14 Significant differences in resistance frequencies, categorized as those at a value of P ≤ 0.05, were determined by defined protocols1 and as described previously.21 Previously published material on gonococcal diseases and their distribution and patterns in Australia, antibiotic usage data and comparable resistance rates in other relevant community-acquired infections was reviewed and relevant information analysed in conjunction with the AMR data.

Results

Numbers and distribution of isolates tested

The AGSP examined 36 258 gonococci in the 10 year period 1 January 1997 to 31 December 2006. Numbers examined in each year ranged between 2817 in 1997 and 3886 in 2005. These numbers represent about two-thirds of all laboratory-based notifications of gonorrhoea annually in Australia.15 Slightly more than half of these isolates came from the states of New South Wales (30%) and Victoria (25%), with the jurisdictions of Western Australia, Queensland, South Australia and the Northern Territory contributing between 5% and 15% of all isolates each. There were only small numbers of gonococci from Tasmania and the Australian Capital Territory in any year. The numbers of isolates by jurisdiction for each year vary slightly14 but by way of illustration those for 2006 were: 1198 and 951 for the states of New South Wales and Victoria (the two most populous jurisdictions); 565, 397 and 244 for Queensland, Western Australia and South Australia, respectively (states with the majority of their population concentrated close to their respective capitals, but each of a large area and with high disease rates in rural populations); 549 from the Northern Territory (again a large area with a low population density but also with high disease rates); 14 from the island state of Tasmania; and 19 from the Australian Capital Territory. Although there have been amalgamations of both public and private sector laboratories over time, the patterns and ultimate source of referrals have altered but little over this period of the programme.

AMR data

Aggregated national trend data over 10 years to 2006 for resistance to the penicillins and ciprofloxacin and for high-level TRNG are shown in Figure 1. There were several significant (P < 0.05) increases and decreases in the proportion of isolates resistant to penicillin and those gonococci non-susceptible to ciprofloxacin from 1997 to 2003 after which there was a continuing and significant increase (as above) in resistance to both antibiotics. Nationally by 2006, over one-third of isolates was resistant to at least one of these agents. The proportion of isolates displaying high-level tetracycline resistance increased more regularly from 5% in 1997 to 12% in 2006. No isolates resistant to spectinomycin were detected in the 10 year period. A total of 134 isolates with ceftriaxone MICs in the less susceptible range (0.06–0.5 mg/L) were detected in urban centres from 2001 to 2006; 108 from New South Wales, 14 from Queensland and 7 from Victoria with small numbers from South Australia, Western Australia and the Northern Territory. Most of these isolates were also multiresistant (to penicillins and quinolones also) and were isolated mainly from overseas travellers or their contacts, but also from domestic transmission.

Figure 1

Aggregated trend data for resistance to the penicillins (by any mechanism), ciprofloxacin non-susceptible gonococci (MIC ≥ 0.06 mg/L) and for high-level tetracycline resistance (TRNG, MIC ≥ 16 mg/L), Australia, 1997–2006.

Figure 1

Aggregated trend data for resistance to the penicillins (by any mechanism), ciprofloxacin non-susceptible gonococci (MIC ≥ 0.06 mg/L) and for high-level tetracycline resistance (TRNG, MIC ≥ 16 mg/L), Australia, 1997–2006.

Disaggregated trend data showing the proportion of PPNG and chromosomally mediated penicillin resistance to penicillin (CMRP) in New South Wales and Victoria and for all penicillin resistance in the Northern Territory are shown in Figure 2, and for isolates less susceptible and resistant to ciprofloxacin in New South Wales and Victoria and all non-quinolone susceptible gonococci in the Northern Territory in Figure 3. These figures contrast resistance patterns in the largely urban samples obtained from New South Wales and Victoria with those seen in the essentially non-urban population of the Northern Territory.

Figure 2

Proportion of penicillinase-producing gonococci (PPNG) and gonococci with chromosomally mediated penicillin resistance (CMRP) in New South Wales (NSW) and Victoria (VIC), and all gonococci penicillin resistant by any mechanism in the Northern Territory (NT), 1997–2006.

Figure 2

Proportion of penicillinase-producing gonococci (PPNG) and gonococci with chromosomally mediated penicillin resistance (CMRP) in New South Wales (NSW) and Victoria (VIC), and all gonococci penicillin resistant by any mechanism in the Northern Territory (NT), 1997–2006.

Figure 3

Proportion of isolates less susceptible (LS) and resistant (R) to ciprofloxacin in New South Wales (NSW) and Victoria (VIC), and all quinolone non-susceptible gonococci in the Northern Territory (NT), 1997–2006.

Figure 3

Proportion of isolates less susceptible (LS) and resistant (R) to ciprofloxacin in New South Wales (NSW) and Victoria (VIC), and all quinolone non-susceptible gonococci in the Northern Territory (NT), 1997–2006.

In New South Wales and Victoria, there were relatively close parallels between trend data for the proportions of PPNG and CMRP present over 10 years (Figure 2). The proportion of PPNG in both centres ranged between 6% and 14% but a much greater volatility was observed for CMRP. Approximately 50% of gonococci tested in each of these centres were penicillin resistant by any mechanism by 2006. In contrast in the Northern Territory, the proportion of penicillin-resistant gonococci (by any mechanism) was substantially lower, <5%. Most of this resistance in the Northern Territory was due to PPNG encountered in travellers or seamen in the coastal capital, Darwin. Very few CMRP were encountered and none in remoter areas of the Territory.

A similar pattern is seen in Figure 3 where the proportion of gonococci less susceptible or else resistant to ciprofloxacin also approximated closely in New South Wales and Victoria. Again, the trend line for gonococci non-susceptible to the quinolones at any MIC level in the Northern Territory was quite dissimilar to that seen in New South Wales and Victoria, and the resistant isolates were almost always from disease acquired external to Australia. The proportion of isolates less susceptible to the quinolones declined to very low levels from 2001 onwards in New South Wales and Victoria, whereas the proportion of resistant strains increased progressively and particularly from 2003 onwards, ultimately approximating 45% of all isolates and mainly from sustained domestic transmission. The ciprofloxacin MICs for the majority of the resistant isolates were between 8 and 64 mg/L in this period.14 In contrast, the proportion of quinolone-resistant N. gonorrhoeae (QRNG) seen in the Northern Territory remained within a narrow range for the entire period and represented imported isolates.

Data from 2006 on resistance to penicillins and ciprofloxacin and TRNG in South Australia and Western Australia, and also disaggregated within these jurisdictions, are shown in Table 1 and compared with national averages. In this example from jurisdictions comprising two of the larger geographic areas in Australia, there is again a significant difference (P < 0.05) between the higher levels of resistance to penicillins and quinolones in metropolitan areas and equivalent data from remote parts of these states.

Table 1

Comparison of the proportions (%) in 2006 of penicillin (PEN all R) and ciprofloxacin (CIP)-resistant gonococci and high-level tetracycline-resistant gonococci (TRNG) in Western Australia (WA) and South Australia (SA) aggregated for each state and for Australia and disaggregated for metropolitan (metro) isolates and rural (non-metro) isolates

State AMR group Aggregated Metro Non-metro 
WA PEN all R 19.2 32.6 3.6 
CIP 16.3 27.8 1.2 
TRNG 28 34.2 7.3 
SA PEN all R 17.3 27 
CIP 27.8 41 
TRNG 6.5 10 
Australia PEN all R 34   
CIP 38   
TRNG 12   
State AMR group Aggregated Metro Non-metro 
WA PEN all R 19.2 32.6 3.6 
CIP 16.3 27.8 1.2 
TRNG 28 34.2 7.3 
SA PEN all R 17.3 27 
CIP 27.8 41 
TRNG 6.5 10 
Australia PEN all R 34   
CIP 38   
TRNG 12   

Disease patterns

Previously published data13,14,22,23 have shown that in large urban settings in Australia, a substantial proportion of gonorrhoea is concentrated in homosexually active men, with smaller contributions to disease numbers from infected travellers and their contacts and the contacts of commercial sex workers. For example, disease rates in inner Sydney health areas, with a high concentration of homosexually active men, were of the order of 60–80/100 000 population, whereas rates in other nearby urban health areas were <10/100 000 population.24 This disease pattern contrasted with the essentially heterosexual disease transmission patterns in non-urban and remote areas where there is little direct or indirect overseas contact but where disease rates may exceed 1000/100 000. These different patterns of disease were reflected in the high male-to-female disease ratio (more than 10:1) and the high proportion of male rectal and pharyngeal isolates examined in urban centres.14 Again this pattern contrasted with a male-to-female disease ratio of 2:1 in regional centres where almost all isolates were from genital tract samples.14

The nature of gonococcal disease in urban and non-urban settings also differed in some important aspects. Higher rates of disseminated gonococcal infection were seen in rural and remote Australia16 and there were recurrent epidemics of gonococcal conjunctivitis in aboriginal toddlers.17 Published and subsequent unpublished data showed the presence of highly dissimilar gonococcal serogroups circulating in Sydney and the Northern Territory.16,25 IA serogroups were significantly more prevalent in the Northern Territory, whereas IB serogroups comprised more than 85% of all isolates in Sydney.

Discussion

In keeping with studies elsewhere,6,7 AMR in N. gonorrhoeae isolated in Australia has increased significantly in recent years, especially to the penicillin and quinolone groups of antibiotics. However, these increases have been uneven and occurred much earlier than equivalent changes in Europe or North America.6,7,9 In remote centres of Australia where oral penicillins still remain the standard treatment regimen, resistance rates were below the critical 5% level for regimen change in the 10 years of this study. In contrast, in a number of the larger urban centres, high rates of penicillin and quinolone resistance were documented prior to the beginning of this study26,27 and this necessitated a shift to treatments based on the injectable cephalosporin, ceftriaxone. During the period of this study, further significant increases in the proportion of gonococci resistant to penicillin and ciprofloxacin occurred in more of the larger urban centres, but after some years discontinuation of these antibiotics as treatment options for gonorrhoea.

In the latter period of this study (2004–06), rapidly increasing resistance to penicillins occurred in urban centres at a time when use of these agents had been discontinued for treatment of gonorrhoea (Figures 1 and 2), and when the general usage of β-lactam antibiotics had also decreased nationally.28 Further, quinolone resistance in N. gonorrhoeae increased to unprecedented levels (in terms of the proportion of resistant strains encountered—for example ∼45% in New South Wales—and the progressively higher MICs recorded for these resistant strains—up to 64 mg/L),14 from 2003 to 2006. Prior to and during this period, general use of quinolone antibiotics for any purpose nationally remained very low in human and animal medicine, mainly because of restrictions on government subsidies for quinolone treatments. Over the same period, results of AMR surveillance of quinolone resistance in other community-acquired pathogens such as Campylobacter sp. from humans and animals29,30 and Escherichia coli from urinary tract infections in Australia31 revealed very low levels of resistance to quinolones in these ‘indicator’ organisms that in other settings have shown significant increases in quinolone resistance following direct or indirect quinolone exposure. However, these community-acquired organisms have markedly less efficient transmission mechanisms than gonococci.

Single-dose programmatic treatment of gonorrhoea helps increase compliance and contain AMR in GC4 although some contend this practice may actually select for AMR.32 Australian data documenting increases in QRNG despite low quinolone usage do not support this contention. However, certain cities in Australia are susceptible to the repeated importation of antibiotic-resistant gonococci highly prevalent in nearby regions.33 The increase in ciprofloxacin resistance over time in Sydney, New South Wales, has been serially documented.2,26,27,34 Over a prolonged period to 1991, continuing importation of diverse subtypes of gonococci with raised ciprofloxacin MICs occurred, but only in low proportions.34 A series of periodic rapid increases in the proportion of QRNG with progressively higher MICs to ciprofloxacin then followed. The QRNG involved comprised a limited number of resistant subtypes that eventually became established in local transmission chains26,27 resulting in their sustained domestic transmission. Although similar events were subsequently described for other overseas centres,7,35 the current pattern of QRNG isolation in Darwin, Northern Territory, corresponds to the much earlier events in Sydney. In remote communities in Australia, there is very little resistance despite highly efficient disease transmission and use of penicillins over many decades. Here, there is little contact with overseas travellers or bridging between rural and urban populations. These communities also have documented clusters of disease uncommonly seen in urban centres16,17 and substantially different gonococcal subtypes.

This combination of an analysis of AMR, demographic, transmission and antibiotic use data together suggests the spread of resistant gonococci occurred in Australia when imported organisms, incidentally but already antibiotic resistant, became established in certain patient subgroups, but for reasons other than antibiotic selection pressures36 and when the relevant antibiotics were no longer in use. Control of AMR in gonococci is difficult because of its capacity for genetic recombination and high transmissibility that includes a significant capacity for regional and international spread.4,37 These factors, when coupled with a propensity to develop AMR through over use and misuse of antibiotics in settings where disease control is also problematic, suggest that broader, global initiatives that integrate both disease and AMR control initiatives are urgently needed.37

Even if the above measures are in place, they will probably only delay rather than prevent emergence of further AMR in gonococci. The Australian data included small numbers of gonococci with decreased susceptibility to ceftriaxone. Other studies show that gonococci with these characteristics are becoming more widespread.35,38,39 The mechanisms of resistance involve altered penA40,41 genes but are not as yet fully elucidated and thus far this resistance appears to impact more on the clinical efficacy of oral third-generation cephalosporins than on ceftriaxone.40–43 If this form of resistance evolves further, efficient methods for its detection and control will need to be in place.44 Continuing surveillance of AMR in N. gonorrhoeae, and at an enhanced level, would thus seem to be prudent despite the considerable technical and logistical difficulties associated with this approach.

Funding

The Department of Health and Ageing of the Commonwealth Government of Australia provides financial assistance to the National Neisseria Network of Australia of which the AGSP is a component. There were no other funding sources.

Acknowledgements

John Bates, Vicki Hicks (Queensland Health Scientific Services, Coopers Plains, Queensland); Tiffany Hogan, Sanghamitra Ray (Department of Microbiology, The Prince of Wales Hospital, Randwick, New South Wales); Julia Griffith, Jocelyn Hibberd, Mark Veitch, Geoff Hogg (The Microbiological Diagnostic Unit (PHL), Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria); Ann Weaver (Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Adelaide, South Australia); Julie Pearson, Hui-Leen Tan (Department of Microbiology and Infectious Diseases, PathWest Laboratory Medicine, Royal Perth Hospital, Western Australia); Mark Gardam, Alistair Macgregor (Department of Microbiology and Infectious Diseases, Royal Hobart Hospital, Hobart, Tasmania); Gary Lum and Microbiology Staff (Microbiology Laboratory, Royal Darwin Hospital, Casuarina, Northern Territory); and Susan Bradbury, Peter Collignon (Microbiology Department, Canberra Hospital, Woden, Australian Capital Territory).

Many other colleagues contributed to various phases of the development of the AGSP, and we thank particularly J. R. L. Forsyth, Margaret Peel and Greg Handke.

Transparency declarations

None to declare.

References

1
Anonymous
Surveillance standards for antimicrobial resistance. WHO/CDS/CSR/DRS/2001.5
2001
Geneva
World Health Organization
 
2
Simonsen
GS
Tapsall
JW
Allegranzi
B
, et al.  . 
The antimicrobial resistance containment and surveillance approach—a public health tool
Bull World Health Organ
 , 
2004
, vol. 
82
 (pg. 
928
-
34
)
3
Tapsall
JW
Monitoring antimicrobial resistance for public health action
Commun Dis Intell
 , 
2003
, vol. 
27
 (pg. 
S70
-
4
)
4
Tapsall
JW
Antimicrobial resistance in Neisseria gonorrhoeae WHO/CDS/CSR/DRS/2001.3
2001
Geneva
World Health Organization
 
5
Roy
K
Wang
SA
Meltzer
MI
Optimizing treatment of antimicrobial resistant Neisseria gonorrhoeae
Emerg Infect Dis
 , 
2005
, vol. 
11
 (pg. 
1265
-
73
)
6
Martin
IMC
Hoffman
S
Ison
CA
European surveillance of sexually transmitted infections (ESSTI): the first combined antimicrobial susceptibility data for Neisseria gonorrhoeae in Western Europe
J Antimicrobial Chemother
 , 
2006
, vol. 
58
 (pg. 
587
-
93
)
7
Centers for Disease Control and Prevention
Update to CDC's Sexually Transmitted Treatment Guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections
MMWR
 , 
2007
, vol. 
56
 (pg. 
332
-
6
)
8
Tapsall
JW
Phillips
EA
Cossins
YM
, et al.  . 
Penicillin sensitivity of gonococci in Australia: the development of an Australian gonococcal surveillance programme
Br J Vener Dis
 , 
1984
, vol. 
60
 (pg. 
226
-
30
)
9
Wang
SA
Harvey
AB
Connor
SM
, et al.  . 
Antimicrobial resistance for Neisseria gonorrhoeae in the United States, 1988 to 2003: the spread of fluoroquinolone resistance
Ann Intern Med
 , 
2007
, vol. 
147
 (pg. 
81
-
8
)
10
GRASP Steeering Group
The gonococcal resistance to antimicrobials surveillance programme (GRASP) year 2005 report
2006
London
Health Protection Agency
 
11
Stathi
M
Flemetakis
A
Miriagou
V
, et al.  . 
Antimicrobial susceptibility of Neisseria gonorrhoeae in Greece: data for the years 1994–2004
J Antimicrob Chemother
 , 
2006
, vol. 
57
 (pg. 
775
-
9
)
12
Tapsall
JW
Phillips
EA
Shultz
TR
, et al.  . 
The incidence of gonorrhoea and the antibiotic sensitivity of gonococci in Australia, 1981–1991
Genitourin Med
 , 
1993
, vol. 
69
 (pg. 
364
-
9
)
13
Tapsall
JW
Phillips
EA
Morris
LM
, et al.  . 
Changing patterns in gonococcal infections in Australia, 1981–1987
Med J Aust
 , 
1988
, vol. 
149
 (pg. 
609
-
12
)
14
Annual reports of the Australian Gonococcal Surveillance Programme
 
15
Samaan
G
Roche
P
Greig
J
, et al.  . 
Evaluation of the Australian Gonococcal Surveillance Programme
Commun Dis Intell
 , 
2005
, vol. 
29
 (pg. 
142
-
8
)
16
Merianos
A
Condon
RJ
Tapsall
JW
, et al.  . 
Epidemic gonococcal conjunctivitis in central Australia
Med J Aust
 , 
1995
, vol. 
162
 (pg. 
178
-
81
)
17
Tapsall
JW
Phillips
EA
Shultz
TR
, et al.  . 
Strain characteristics and antibiotic susceptibility of isolates of Neisseria gonorrhoeae causing disseminated gonococcal infection in Australia
Int J STD AIDS
 , 
1992
, vol. 
3
 (pg. 
273
-
7
)
18
Merlino
J
Tapsall J and members of the National Neisseria Network of Australia
Animicrobial testing and applications in the pathogenic Neisseria
Antimicrobial Susceptibility Testing: Methods and Practices With An Australian Perspective
 , 
2004
Sydney
Australian Society for Microbiology
(pg. 
175
-
88
)
19
Tapsall
JW
Phillips
EA
Cossins
YM
, et al.  . 
Use of a quality assurance scheme in a long-term multicentric study of antibiotic susceptibility of Neisseria gonorrhoeae
Genitourin Med
 , 
1990
, vol. 
66
 (pg. 
437
-
44
)
20
Ison
CA
Terry
P
Bendayna
K
, et al.  . 
Tetracycline-resistant gonococci in the UK
Lancet
 , 
1988
, vol. 
i
 (pg. 
651
-
2
)
21
Limnios
EA
Nguyen
N-L
Ray
S
, et al.  . 
Dynamics of appearance and expansion of a prolyliminopeptidase-negative subtype among Neisseria gonorrhoeae isolates collected in Sydney, Australia, from 2002 to 2005
J Clin Microbiol
 , 
2006
, vol. 
44
 (pg. 
1400
-
4
)
22
Sherrard
J
Forsyth
J
Homosexually acquired gonorrhoea in Victoria, 1983–1991
Med J Aust
 , 
1993
, vol. 
158
 (pg. 
182
-
90
)
23
Donovan
B
Bodsworth
NJ
Rohrsheim
R
, et al.  . 
Characteristics of homosexually active men with gonorrhoea during an epidemic in Sydney, Australia
Int J STD AIDS
 , 
2001
, vol. 
12
 (pg. 
437
-
43
)
24
Report of the New South Wales Chief Health Officer
Communicable diseases, gonorrhoea
New South Wales public Health Bulletin
 
25
Lum
G
Freeman
K
Nguyen
NL
, et al.  . 
A cluster of culture positive gonococcal infections but with false-negative cppB-gene-based PCR
Sex Transm Infect
 , 
2005
, vol. 
81
 (pg. 
400
-
2
)
26
Tapsall
JW
Phillips
EA
Shultz
TR
, et al.  . 
Quinolone resistant Neisseria gonorrhoeae isolated in Sydney, Australia 1991–1995
Sex Transm Dis
 , 
1996
, vol. 
23
 (pg. 
425
-
8
)
27
Tapsall
JW
Limnios
EA
Shultz
TR
Continuing evolution of the pattern of quinolone resistance in Neisseria gonorrhoeae isolated in Sydney, Australia
Sex Transm Dis
 , 
1998
, vol. 
25
 (pg. 
415
-
7
)
28
Commonwealth of Australia
The use of antibiotics in food-producing animals: antibiotic resistant bacteria in animals and humans
Report of the Joint Expert Advisory Committee on Antibiotic Resistance (JETACAR)
 , 
1999
 
http://www.health.gov.au/pubs/jetacar.htm (30 July 2007, date last accessed)
29
Unicomb
L
Ferguson
J
Riley
TV
, et al.  . 
Fluoroquinolone resistance in Campylobacter absent from isolates, Australia
Emerg Infect Dis
 , 
2003
, vol. 
9
 (pg. 
1482
-
3
)
30
Miflin
JK
Templeton
JM
Blackall
PJ
Antibiotic resistance in Campylobacter jejuni and Campylobacter coli from poultry in the South-East Queensland region
J Antimicrob Chemother
 , 
2007
, vol. 
59
 (pg. 
775
-
8
)
31
Turnidge
J
McCarthy
LR
Master
RN
, et al.  . 
Low levels of fluoroquinolone resistance in Escherichia coli. A five-year trend in Australia through use of TSN database Australia
Commun Dis Intell
 , 
2003
, vol. 
27
 
Suppl
(pg. 
S89
-
91
)
32
Livermore
DM
Minimising antibiotic resistance
Lancet Infect Dis
 , 
2005
, vol. 
5
 (pg. 
450
-
9
)
33
The WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme
Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 2005
Commun Dis Intell
 , 
2006
, vol. 
30
 (pg. 
430
-
3
)
34
Tapsall
JW
Shultz
TR
Phillips
EA
Characteristics of Neisseria gonorrhoeae isolated in Australia showing decreased sensitivity to quinolone antibiotics
Pathology
 , 
1992
, vol. 
24
 (pg. 
27
-
31
)
35
Wang
SA
Lee
MVC
O'Connor
N
, et al.  . 
Multi-drug resistant Neisseria gonorrhoeae with decreased susceptibility to cefixime—Hawaii, 2001
Clin Infect Dis
 , 
2003
, vol. 
37
 (pg. 
849
-
52
)
36
Rowbottom
JH
Tapsall
JW
Plummer
DC
, et al.  . 
An outbreak of a penicillin-sensitive strain of Neisseria gonorrhoeae in Sydney men
Genitourin Med
 , 
1994
, vol. 
70
 (pg. 
196
-
9
)
37
Tapsall
J
Antibiotic resistance in Neisseria gonorrhoeae is diminishing available treatment options for gonorrhea: some possible remedies
Expert Rev Anti Infect Ther
 , 
2006
, vol. 
4
 (pg. 
619
-
28
)
38
Akasaka
S
Muratani
T
Yamada
Y
, et al.  . 
Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce β-lactamase
J Infect Chemother
 , 
2001
, vol. 
7
 (pg. 
49
-
50
)
39
Bala
M
Ray
K
Gupta
SM
, et al.  . 
Changing trends of antimicrobial susceptibility patterns of Neisseria gonorrhoea in India and the emergence of ceftriaxone less susceptible N. gonorrhoeae strains
J Antimicrob Chemother
 , 
2007
, vol. 
60
 (pg. 
582
-
6
)
40
Ito
M
Deguchi
T
Mizutani
KS
, et al.  . 
Emergence and spread of Neisseria gonorrhoeae clinical isolates harboring mosaic-like structure of penicillin-binding protein 2 in Central Japan
Antimicrob Agents Chemother
 , 
2005
, vol. 
49
 (pg. 
137
-
43
)
41
Whiley
DM
Limnios
EA
Ray
S
, et al.  . 
Diversity of penA alterations and subtypes of Neisseria gonorrhoeae less susceptible to ceftriaxone from Sydney, Australia
Antimicrob Agents Chemother
 , 
2007
, vol. 
51
 (pg. 
3111
-
6
)
42
Tanaka
M
Nakayama
H
Huruya
K
, et al.  . 
Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype
Int J Antimicrob Agents
 , 
2006
, vol. 
27
 (pg. 
20
-
6
)
43
Ochiai
S
Sekiguchi
S
Hayashi
A
, et al.  . 
Decreased affinity of mosaic-structure recombinant penicillin-binding protein 2 for oral cephalosporins in Neisseria gonorrhoeae
J Antimicrob Chemother
 , 
2007
, vol. 
60
 (pg. 
54
-
60
)
44
Whiley
D
Bates
J
Limnios
A
, et al.  . 
Use of a novel screening PCR indicates presence of a mosaic penA gene sequence in Australia
Pathology
 , 
2007
, vol. 
39
 (pg. 
445
-
6
)

Author notes

See the Acknowledgements section.