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Table 1 Sources and study methodology of benzylpenicillin, ceftriaxone and azithromycin MIC data used in the study

From: Where have all the susceptible gonococci gone? A historical review of changes in MIC distribution over the past 75 years

Country/

EUCAST

Antimicrobial

Sampling period

Study design, testing modality and study reference

References

Denmark

Benzylpenicillin

1944 & 1957

1944: 90 strains from 90 non-selected patients stored as lyophilized cultures and tested in 1957 in parallel with and using the same methodology as the 1957 samples as detailed below.

1957: 103 isolates from 96 randomly-selected patients. Benzylpenicillin susceptibility was assessed using the plate dilution and tablet methods. The two methods provided highly concordant results. Results are reported as 50% inhibitory concentrations for the plate dilution method which provided the most reproducible results. The 50% inhibitory concentrations were calculated by means of the Karber method.

[16]

Japan

Benzylpenicillin

1968

33 gonococcal isolates from 33 consecutive navy personnel attending a USA navy STI clinic at Yokosuya, Japan, with a diagnosis of urethritis. MICs were determined via agar dilution following CLSI guidelines.

[17]

2009–2010

83 isolates from 83 individuals with gonococcal male urethritis presenting to one of 51 facilities in Japan between April 2009 and October 2010 were sent to a central laboratory for benzylpenicillin MIC testing via agar dilution in accordance with CLSI guidelines.

[18]

Ceftriaxone

1995–2005

MICs were determined using an agar dilution method with a GC agar base containing 1% defined growth supplement. Performed on 690 clinical isolates of N. gonorrhoeae obtained from local STI clinics between 1995 and 2005 in Kanagwa, Japan.

[19]

2010–2013

MICs were determined using an agar dilution method with a GC agar base containing 1% defined growth supplement. Performed on 677 clinical isolates of N. gonorrhoeae obtained from the local STI clinic between January 2010 to December 2013 in Fukuoka, Japan.

[3]

Azithromycin

1981 to 1984 and 1992 to 1993

27 isolates from 1981 to 1984 and 79 isolates from 1992 to 1993 had their MICs determined simultaneously via the same methodology via an agar dilution method with a GC agar base containing 1% defined growth supplement.

[20]

2013

137 isolates from consecutive male and female patients attending STI clinics in Fukuoka, with ‘genital gonorrhoea’. Susceptibility testing was performed via agar dilution with GC agar.

[3].

2014/2015

Study performed on 60 isolates from 2014 and 54 isolates from 2015. All isolates were from males with a confirmed case of gonococcal urethritis. Azithromycin MICs were determined via the agar dilution method using GC agar base media supplemented with 1% IsoVitaleX.

[11]

South Africa

Benzylpenicillin

1976–77

175 isolates from non-selected men with urethritis presenting to a GUM clinic in Johannesburg between 1976 and 1977. MICs tested via agar diffusion using Oxoid DST agar.

[20] [18]

2013

319 isolates from men with urethritis and women with vaginal discharge syndrome presenting to two GUM clinics in Durban and Pietermaritzburg. MICs were tested using the agar dilution method. MICs tested via agar diffusion using Oxoid DST agar.

[21]

Azithromycin

1999

56 isolates from men with urethritis and women with vaginal discharge syndrome presenting to a single GUM clinic in Durban. MIC testing was performed with agar diffusion using Oxoid DST agar.

[22]

2013

319 isolates from men with urethritis and women with vaginal discharge syndrome presenting to two GUM clinics in Durban and Pietermaritzburg. MICs were tested using the agar dilution method. MICs tested via agar diffusion using Oxoid DST agar.

[21]

Ceftriaxone

1995 & 1999

In 1995, 61 isolates and in 1999 58 isolates from men with urethritis and women with vaginal discharge syndrome presenting to a single GUM clinic in Durban. MIC testing was performed with agar diffusion using Oxoid DST agar.

[22]

2013

319 isolates from men with urethritis and women with vaginal discharge syndrome presenting to two GUM clinics in Durban and Pietermaritzburg. MICs were tested using the agar dilution method. MICs tested via agar diffusion using Oxoid DST agar.

[21]

UK

Benzylpenicillin

1957

Taken from a report produced by the Medical Research Council Working Party to Examine the Resistance of Gonococci to Benzylpenicillin. Results for 302 isolates taken in the London area in April to December 1957 are provided. All samples were tested centrally via the same agar diffusion technique.

[23]

1994

Isolates were from 113 consecutive patients attending the GUM clinic at an East London GUM clinic over a one-year period. 66% were from men and 3.5% MSM. MICs were determined by agar diffusion.

[24]

2001

In the 2001 Gonococcal resistance to antimicrobials surveillance programme (GRASP) report, 2542 isolates from 24 participating GUM clinics had their MICs ascertained via agar diffusion using Oxoid DST agar.

[25]

Ceftriaxone

2003, 2008 and 2015

2003 results are taken from Gonococcal resistance to antimicrobials surveillance programme (GRASP) Report 2003. In this survey 1977 non-duplicate isolates had MIC testing performed with agar diffusion using Oxoid DST agar.

Results for 2008 and 2015 are taken from the 2016 Gonococcal resistance to antimicrobials surveillance programme (GRASP) report [26]. 2008 data: 1276 isolates were tested from 26 GUM clinics in England and Wales. MIC testing performed with agar diffusion using Oxoid DST agar. No further details provided.

2015 data: 2302 isolates from 1699 unique patients from 23 English GUM clinics were tested. 87% were men and 72% were MSM. Slight over-representation of MSM and London residents. MIC testing performed with agar diffusion using HiMedia DST agar.

[26,27,28]

Azithromycin

2001

In the 2001 Gonococcal resistance to antimicrobials surveillance programme (GRASP) report, 2542 isolates from 24 participating GUM clinics had their MICs ascertained via agar diffusion using Oxoid DST agar. 71% were men and 25% MSM.

[25]

2003

2003 results are taken from Gonococcal resistance to antimicrobials surveillance programme (GRASP) Report 2003. In this survey 1977 non-duplicate isolates had MIC testing performed with agar diffusion using Oxoid DST agar. 72% were from men and 24% from MSM. 47.1% were from London and 52.9% from outside London. Azithromycin MIC distributions for the whole country were not provided but distributions for both London and non-London populations were provided. These were similar and we use the data for the non-London sample as this was larger.

[28]

2015

2302 isolates from 1699 unique patients from 23 English GUM clinics were tested. 87% were men and 72% were MSM. Slight over-representation of MSM and London residents. MIC testing performed with agar diffusion using HiMedia DST agar

[26]

USA

Benzylpenicillin

1945

104 isolates from a non-selected group of female patients with a diagnosis of gonorrhoea attending a clinic at the University of Texas. MIC were tested via agar dilution on 0.5% starch agar.

[29]

Pre-1947 and 1949

A study from a single laboratory in Boston that used the same MIC methodology (agar dilution) to test susceptibility for gonococcal isolates obtained before 1947 (n = 24) with those from 1949 (n = 52). Isolates were from men and women. Heart-infusion agar was used in all assessments.

[30]

Benzylpenicillin, azithromycin & ceftriaxone

1987/1988, 1992, 2013 & 2017

The typical annual Gonococcal Isolate Surveillance Project (GISP) methodology is as follows: Isolates are collected monthly from up to the first 25 men with N. gonorrhoeae urethritis attending participating STD clinics. Isolates are sent to the regional laboratories for agar dilution antimicrobial susceptibility testing.

GISP 1987 (benzylpenicillin/ceftriaxone): 6204 isolates from men with urethritis from 21 clinics presenting between September 1987 and December 1988. MICs were ascertained at 4 central laboratories using the agar-dilution technique with GC-II Base medium [31].

GISP 1992 (Azithromycin) Susceptibility testing for azithromycin in GISP began in 1992. GISP 1992 tested 5238 gonococcal isolates [32, 33]

GISP 2013: (ceftriaxone/azithromicin): In GISP 2017 STD clinics affiliated with 27 state or city health departments sent 5093 gonococcal isolates to GISP.

GISP 2017 (ceftriaxone/azithromicin): In GISP 2017 STD clinics affiliated with 27 state or city health departments contributed 5061 gonococcal isolates to GISP.

[34]

EUCAST collections

Azithromycin

3727 isolates from 10 collections

[14]

Benzylpenicillin

11,826 isolates from 21 collections

[14]

Ceftriaxone

1697 isolates from 11 collections

[14]

  1. Abbreviations: GISP - Gonococcal Isolate Surveillance Project; GRASP - Gonococcal resistance to antimicrobials surveillance programme; GUM - GenitoUrinary Medicine Clinic; MSM -Men who have sex with men; STD -Sexually Transmitted Diseases