Background: Neisseria gonorrhoeae (N. gonorrhoeae) is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of N. gonorrhoeae has become a serious public health problem. The accuracy of molecular detection for detecting moderate-level azithromycin resistance is not well-established. We summarized the data from studies of the N. gonorrhoeae 23S rRNA mutation at position 2611 with azithromycin resistance to determine the relationship between the mutation and resistance. Methods and Findings: In this systematic review and meta-analysis, two researchers independently searched six databases for studies with data for the azithromycin minimum inhibitory concentrations (MICs) and the 23S rRNA mutation C2611T of each N. gonorrhoeae isolate. Since the breakpoint of moderate-level resistance to azithromycin (ML-AzmR) was not determined, we divided the moderate level into two groups according to the range of MICs (moderate resistance limited to 2–128 mg/L or 4–128 mg/L) for data extraction. A random-effects model was used to calculate the pooled sensitivity rate, the specificity rate, the pooled positive likelihood ratio (PLR), the negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR). Meta-regression analyses by detection method, isolates sampling (a random sample or not), location, and sample size were performed to explore the possible causes of heterogeneity. The potential publication bias of the included studies was conducted by the Deeks’ test. We included 20 studies in our study: 20 studies have data of N. gonorrhoeae with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of N. gonorrhoeae with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2–128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6–74%), the pooled specificity rate was 98.7% (95% CI, 98.2–99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4–128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9–94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1–96.6%), and the DOR ranged from 41.9 to 364.1 (mean, 123.6). Conclusion: Through this meta-analysis, we found that the C2611T mutation of 23S rRNA is valuable for the molecular diagnostic of moderate-level azithromycin resistance (ML-AzmR) in N. gonorrhoeae, especially when the moderate level is set at 4–128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.

Purpose: This study aimed to determine the minimum inhibitory concentrations (MICs) of ertapenem on Neisseria gonorrhoeae collected from eight Chinese provinces in 2018. Methods: The MICs of ertapenem on 503 Neisseria gonorrhoeae isolates (415 isolates selected randomly and 88 isolates selected with preference) were measured using the agar dilution method. For comparison, the MICs of ceftriaxone and azithromycin were detected. Results: Among 415 randomly selected isolates, the MIC range for ertapenem was from ≤ 0.008 mg/L to 0.5 mg/L. The corresponding MIC₅₀ and MIC₉₀ were 0.06 and 0.125 mg/L, respectively. Twelve of 415 isolates (2.9%) exhibited MIC values ≥ 0.25 mg/L, and only one isolate (0.2%) had a MIC of 0.5 mg/L. By comparing all 503 tested isolates, a correlation of r = 0.487 (P < 0.001) between ertapenem and ceftriaxone MIC was observed, and the correlation between MICs of ertapenem and azithromycin was low (r = − 0.12, P = 0.007). In 24 ceftriaxone-decreased susceptibility isolates, four isolates (16.7%) showed a MIC ≥ 0.25 mg/L for ertapenem. In 85 azithromycin resistant isolates, three isolates (3.5%) showed a MIC ≥ 0.25 mg/L for ertapenem. Conclusion: The in vitro results suggest that ertapenem has satisfactory susceptibility in isolates collected from eight provinces in China; hence, it might be a promising treatment option for resistant gonococcal infections.

The susceptibility to gentamicin of N. gonorrhoeae isolates collected in three Chinese provinces and the correlation among the MICs of gentamicin, azithromycin, and ceftriaxone were investigated in this study. The effects of combinations from those three antibiotics were also in the scope of this study to determine the efficacy of gentamicin as a combination therapeutic drug. The agar dilution method was used to measure the minimum inhibitory concentrations (MICs) of ceftriaxone, azithromycin and gentamicin on N. gonorrhoeae isolates. The synergy between these three antimicrobials were determined using the agar dilution checkerboard method. Subgroup studies were conducted to explore differences between azithromycin- and ceftriaxone-sensitive and resistant isolates. A total of 139 (36.60%) and 233 (61.30%) isolates demonstrated full susceptibility and intermediate susceptibility to gentamicin, respectively. The correlation analysis showed that the MICs of ceftriaxone and azithromycin weakly correlated with the value of gentamicin. The overall results of the three antibiotic combinations revealed indifferent effects. Combination therapy established a significant reduction on the MIC value. Most of the N. gonorrhoeae isolates tested in this study demonstrated a certain degree of susceptibility to gentamicin. Overall, antimicrobial combinations of gentamicin with ceftriaxone or azithromycin demonstrate indifferent effects.

Purpose: The increasing drug resistance of Neisseria gonorrhoeae has become a serious public health concern. This study investigated N. gonorrhoeae isolates susceptibility to tetracycline antibiotics and the correlation between minimum inhibitory concentrations (MICs) of different antibiotics. The presence of resistance determinants in N. gonorrhoeae strains displaying different levels of tigecycline resistance was also compared. Methods: The minimum inhibitory concentrations (MICs) of tetracycline, minocycline, tigecycline, eravacycline, omadacycline on 412 N. gonorrhoeae isolates were measured by the agar dilution method. The MICs of ceftriaxone and azithromycin were also measured to determine the correlations between antibiotics by the value of the correlation coefficient R. The presence of resistance determinants was identified through polymerase chain reaction (PCR) and sequencing. Results: The MIC₉₀ was 64mg/L for tetracycline, 64mg/L for minocycline, 0.5mg/L for tigecycline, 0.5mg/L for eravacycline, 4mg/L for omadacycline, 0.25 mg/L for ceftriaxone, and 1mg/L for azithromycin. The MIC₉₀ and mode of tigecycline and eravacycline were much lower than those of tetracycline and minocycline. A poor correlation between omadacycline, eravacycline and tetracycline susceptibility was observed. Minocycline has a strong correlation with tetracycline. PorB1 typing, TetM-encoding plasmid, and mtrR promoter adenine deletion were significantly correlated with tigecycline MIC > 0.25mg/L. Conclusion: This study suggested that tigecycline and eravacycline had better in vitro activity and might be alternative antibiotics against resistant N. gonorrhoeae infections. Nevertheless, further in vitro experiments and clinical studies are needed for verification.