Table 3.
Laboratory studies of Mycoplasma genitalium antimicrobial susceptibility and genotypic resistance testing
| Reference | Year | Study type | Population | M. genitalium DNA extracts or isolates examined (n) | Macrolide resistance (MIC data/resistance mutationsa) | Fluoroquinolone resistance (MIC data/resistance mutationsb) | Comments |
|---|---|---|---|---|---|---|---|
| Bradshaw et al28 | 2006 | Prospective case–control study | 9 men with NGU attending an STI clinic, Australia | 4 isolates | All 4 isolates had raised MICs to macrolides (AZM >8 mg/L, ERY >32 mg/L, CAM >32 mg/L) | Not applicable | 8/9 men experienced improvement/resolution of symptoms before NGU recurrence; one was persistently asymptomatic |
| Jensen et al32 | 2008 | Laboratory analysis |
M. genitalium DNA extracts and isolates from 12 men with NGU who failed AZM therapy in Australia, Norway, and Sweden 7 AZMS genetically distinct control strains, Sweden |
12 AZMR DNA extracts 7 clinical isolates 7 control strains |
7/7 isolates persisting after azithromycin therapy had raised MICs to macrolides (AZM ≥8 mg/L, ERY ≥16 mg/L, CAM ≥16 mg/L) 12 23S rRNA gene mutations reported: 5 at position 2059 (all A2059G); 5 at position 2058 (4 A2058G, one A2058C) |
Not applicable | None |
| Chrisment et al40 | 2012 | Uncontrolled retrospective study | 136 patients with M. genitalium infection attending STI clinics, general practice clinics, and hospitals, France | 115 DNA extracts | 13 23S rRNA gene mutations reported: 9 at position 2059 (6 A2059G, 2 A2059T, 1 A2059C); 2 at position 2058 (2 A2058G); 1 at position A2062T; 1 at position C2038T |
Not applicable | None |
| Shimada et al60 | 2010 | Uncontrolled retrospective study | 308 men with NGU attending a urology clinic, Japan | 28 DNA extracts | Not applicable | Single substitutions reported in the gyrA gene at position 321 (T321A) in 2 specimens Single substitutions reported in the parC gene of 4 specimens: G248A, G259T, A260T, A290G | None |
| Shimada et al34 | 2011 | Uncontrolled retrospective study | 308 men with NGU attending a urology clinic, Japan | 25 DNA extracts | 4 23S rRNA gene mutations reported: 1 at position 2059 (A2059G); 3 at position 2185 (T2185G) | Not applicable | The A2158G mutation is not associated with macrolide resistance in other bacteria. Amino acid substitutions reported in the L4 and L22 ribosomal proteins of unknown significance. The strain with the A2059G mutation was cured with AZM 1 g |
| Ito et al7 | 2011 | Laboratory analysis | 7 men with M. genitalium related NGU which failed AZM therapy at a urology clinic, Japan | 7 DNA extracts | 4 23S rRNA gene mutations reported: 2 at position 2059 (A2059G); 2 at position 2058 (A2058G) | Not applicable | All 7 men had no AZMR mutations in pretreatment M. genitalium DNA extracts. One of the M. genitalium strains with the A2058G mutation also had a L4 protein mutation |
| Walker et al35 | 2013 | Longitudinal study | 1,100 women attending 29 primary care clinics, Australia | 33 DNA extracts | Unspecified 23S rRNA gene mutations were reported in 2/27 pretreatment samples from patients cured with AZM 1 g stat, and also in the test-of-cure samples of 3/3 patients who failed AZM 1 g stat therapy | Not applicable | Women were recruited in the Chlamydia Incidence and Re-infection Rates Study. There were 27 baseline, 14 follow-up, and 3 positive test-of-cure specimens |
| Twin et al31 | 2012 | Laboratory analysis | 82 pretreatment and 20 post-treatment samples from patients with clinical treatment failure attending an STI clinic, Australia | 102 DNA extracts | 16/82 pretreatment samples had 23S rRNA gene mutations (A2058G, A2059G, A2059C) 20/20 post-treatment samples from patients failing AZM therapy had 23S rRNA gene mutations (12 A2059G, 7 A2058G, 1 A2059C) | Not applicable | Mutations detected by high resolution melt analysis that may not have been able to detect the type 4 SNP (A-to-T) at position 2058 |
| Gesink et al39 | 2012 | Uncontrolled observational study | 314 participants recruited through telephone and community initiatives, Greenland | 26 DNA extracts | Single 23S rRNA gene mutations reported in 26/26 M. genitalium cases tested: 17 at position 2058 (A2058G); 9 at position 2059 (A2059G) | Not applicable | None |
| Tagg et al33 | 2013 | Laboratory analysis | 143 initial and 43 follow-up M. genitalium-positive samples from 167 patients attending STI clinics, Australia | 186 DNA extracts | 62/143 (43.4%) initial DNA extracts had 23S rRNA gene mutations at either position 2058 (21 A2058G, 2 A2058T, 1 A2058C), or 2059 (38 A2059G) Follow-up DNA extracts of 23/24 (95.8%) patients had 23S rRNA gene mutations |
1/143 (0.7%) had gyrA mutations (G285C) resulting in an amino acid changes 22/143 (15.4%) initial DNA extracts had parC mutations (11 G248T, 3 G259A, 2 G259T, 1 G241T, 1 G244A, 1 A247C, 1 G259C, 1 A260G, 1 G307A) resulting in amino acid changes Follow-up DNA extracts from 3/24 (12.5%) patients had gyrA/parC mutations |
The matched initial DNA extract for 8/23 follow-up specimens with 23S rRNA mutations did not have evidence of these same AZMR mutations |
| Couldwell et al36 | 2013 | Uncontrolled observational study | 33 patients attending a STI clinic with M. genitalium infections, either as NGU cases (30 men) or their sexual partners (2 women, 1 man), Australia | 32 DNA extracts | 15/32 (46.9%) had 23S rRNA gene mutations at position 2058 (A2058G, A2058T) or position 2059 (A2059G) | 6/32 (18.8%) had gyrA mutations (G285C) or parC mutations (G248T, G259A, A260G) | Transmitted macrolide resistance was reported in 4/20 (20.0%) of samples from patients who had not received AZM pretreatment. None of the study group reported prior fluoroquinolone use |
| Yew et al8 | 2011 | Laboratory analysis | 11 M. genitalium DNA extracts from men with recurrent NGU, New Zealand | 9 DNA extracts | 4/9 (44.4%) had A2059G mutations in the 23S rRNA gene | Not applicable | Unable to amplify 23S rRNA genes of 2/11 known M. genitalium-positive DNA extracts |
| Anagrius et al30 | 2013 | Uncontrolled retrospective study | 11 patients testing positive for M. genitalium after treatment with azithromycin 1 g single-dose (n=10) or extended azithromycin 1.5 g (n=1) therapy, Sweden | 8 DNA extracts | 1/8 (12.5%) pretreatment and 8/8 (100.0%) post-treatment samples had non-specified macrolide-associated 23S rRNA gene mutations | Not applicable | 2/10 pretreatment samples were missing and 1/10 pretreatment samples had insufficient DNA for amplification. The patient failing the extended azithromycin had macrolide mutations in the pretreatment DNA extract |
| Pond et al41 | 2014 | Uncontrolled observational study | 217 men with urethritis-related symptoms, UK | 22 DNA extracts | 23S rRNA gene mutations reported in 9/22 (40.9%) samples: 5 at position 2058 (A2058G); 9 at position 2059 (3 A2059G, 1 A2059C) | 1/22 (4.5%) had a parC mutation (A247C) | None |
| Kikuchi et al38 | 2014 | Laboratory analysis | 90 M. genitalium DNA extracts from men with NGU, Japan | 68 DNA extracts (macrolide resistance testing) 51 DNA extracts (fluoroquinolone resistance testing) |
23S rRNA gene mutations reported in 5/68 (7.4%) samples: 4 at position 2058 (A2058G); 1 at position 2059 (A2059G) | 5/51 (9.8%) had gyrA mutations (4 C267T, 1 C270T); 18/51 (35.3%) had parC mutations (12 G248A, 3 G248T, 2 G259A, 1 C356A) | The significance of the reported C356A mutation is unclear as it is outside the fluoroquinolone resistance-determining region |
| Salado-Rasmussen and Jensen13 | 2014 | Uncontrolled retrospective survey | 1,008 patients from general practice, private specialists and hospitals with M. genitalium infection, Denmark | 1,085 DNA extracts | 385/1,008 (35.5%) patients had macrolide resistance; A2058G (61%) and A2059G (35%) were the most common mutations | Not applicable | None |
| Hay et al42 | 2015 | Laboratory analysis | 601 women attending primary health care clinics, South Africa | 41 DNA extracts | A2058G mutations reported in the 23S rRNA gene of 4/41 (9.8%) DNA extracts tested | Not applicable | None |
Notes:
a
Mutation positions are according to Escherichia coli numbering;
b
mutation positions are according to M. genitalium G37 genome (GenBank accession number NC000908.2).
Abbreviations: M. genitalium, Mycoplasma genitalium; NGU, non-gonococcal urethritis; STI, sexually transmitted infection; AZM, azithromycin; CAM, clarithromycin; ERY, erythromycin; AZMS, azithromycin-susceptible; AZMR, azithromycin-resistant; SNP, single nucleotide polymorphism; MIC, minimum inhibitory concentration.