Susceptibilities of Neisseria gonorrhoeae to the glycylcyclines (original) (raw)
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Evaluation of the in vitro activity of six antimicrobial agents against Neisseria gonorrhoeae
Revista do Instituto de Medicina Tropical de São Paulo, 2007
Use of antimicrobials for the treatment of gonorrhea started in 1930 with the utilization of sulfonamides. With the years other drugs were used for its treatment such as penicillin, tetracycline, spectinomycin, and others. Although highly specific in the beginning, these drugs, with time did not show anymore the expected therapeutic results because of aspects of chromosomal and plasmid-mediated resistance. The purpose of this study was to evaluate the susceptibility of Neisseria gonorrhoeae strains to six drugs used for its treatment (penicillin, tetracycline, cefoxitin, thiamphenicol, spectinomycin and ofloxacin) by the determination of minimal inhibitory concentrations of these drugs. We concluded that drugs, such as cefoxitin, thiamphenicol and spectinomycin still are excellent pharmacological agents for the treatment of gonorrhea. Penicillin, although still efficient, needs more attention regarding its use, as well as ofloxacin, because of the emergence of resistant strains. Tetracycline and its derivatives should be strongly contraindicated for the treatment of gonorrhea.
Sexually Transmitted Infections, 1992
Objective: To investigate the in vitro antimicrobial susceptibility and resistant trends of Neisseria gonorrhoeae strains isolated in Guangzhou, from 1996 to 2001. Methods: The agar dilution method was used to determine the minimum inhibitory concentrations (MICs) to four antimicrobials, penicillin G, ciprofloxacin, ceftriaxone, and spectinomycin. The resistance of all strains to four antibiotics was interpreted according to criteria used in the project of surveillance of gonococcal antibiotic susceptibility in the WHO Western Pacific Region. Penicillinase producing N gonorrhoeae (PPNG) was analysed by the paper acidometric method. Results: 793 consecutive N gonorrhoeae isolates collected in Guangzhou were studied from 1996 to 2001. A total of 55 strains of PPNG were identified and the prevalence rapidly spread from 2% to 21.8%. Of the four antibiotics examined, ceftriaxone and spectinomycin appeared to be the most effective agents although two spectinomycin resistant strains were isolated in 1996. Their MIC 50 , MIC 90 , and geometric mean MIC (MICmean) were all between the sensitive ranges of the interpretative criteria and remained stable over the years. However, resistance increased continuously to penicillin G and dramatically to ciprofloxacin. In 1996 , and MICmean of penicillin G increased from 1 mg/ml to 2 mg/ml, 4 mg/ml to 32 mg/ml, and 0.68 mg/ml to 2.35 mg/ml, respectively; those of ciprofloxacin steeply increased from 0.12 mg/ml to 4 mg/ml, 2 mg/ml to 32 mg/ml, and 0.14 mg/ml to 2.62 mg/ml in 1996-9, respectively, and then declined slightly in 2000-1. The prevalence of resistant isolates spread from 57.2% to 81.8% for penicillin G and from 17.6% to 72.7% for ciprofloxacin over the 6 years. Conclusion: Resistance to penicillin and ciprofloxacin increased greatly during 1996-2001. Ceftriaxone and spectinomycin should be used as the first line agents in treating gonorrhoea. It is of great importance to continuously survey the susceptibilities of N gonorrhoeae to antibiotics in controlling the spread of gonococcal infections.
Tetracycline resistance of Neisseria gonorrhoeae in Russia, 2015–2017
Infection, Genetics and Evolution, 2018
The objective of this study was to estimate the tetracycline resistance level in the modern population of Neisseria gonorrhoeae in the Russian Federation, where this drug was removed from the treatment regimen for gonococcal infections in 2003. A total of 401 isolates collected between 2015 and 2017 were analyzed for genetic markers (chromosomal porB, rpsJ and mtrR gene mutations and the plasmid-located tetM gene) involved in tetracycline resistance. Antibiotic susceptibility testing revealed that 19% of the strains were tetracycline resistant (MIC > 1 mg/L) and that 10% of the strains had intermediate susceptibility (0.5 < MIC ≤ 1 mg/L). Various combinations of mutations identified in the rpsJ (Val57Met/Leu), porB (Gly120Lys/Asp/Asn/Thr and Ala121/ Asp/Asn/Gly), and mtrR (−35 del A) genes resulted in MIC increases of up to 1.47 mg/L (geometric mean value). The presence of the tetM gene was detected in 29 strains, including 18 tetM genes of the American type and 11 of the Dutch type. The tetM gene was associated with a strong increase in resistance (MIC > 8 mg/L). One N. gonorrhoeae isolate was found to carry a defective tetM gene with an AG deletion at position 1239-1240, а new stop codon was introduced that caused a defect in TetM protein synthesis and decrease in the tetracycline resistance. Phylogenetic trees constructed using N. gonorrhoeae NG-MAST and tetM loci were compared. Complex relationship was observed between the N. gonorrhoeae sequence type and the tetM plasmid type. Partial recovery of N. gonorrhoeae tetracycline susceptibility was observed relative to the proportion of isolates with resistance detected ten years ago (75%). However, the current levels of tetracycline resistance still preclude the renewed use of these drugs for gonococcal infection therapy.
In-vitro activity of antimicrobial agents against Neisseria gonorrhoeae in Brussels
The minimum inhibitory concentrations (MICs) of 18 antimicrobial agents against 104 strains of Neisseria gonorrhoeae isolated in the Brussels area between January and October 1976 have been measured. The MICs for penicillin G, ampicillin, amoxycillin, carbenicillin, and cephalexin showed a bimodal distribution. The second modus strains of cephalexin (MIC=6-25 ,ug/ml) were relatively resistant to penicillin G (MIC>0'08 ,tg/ml). About 51 % of all strains were relatively resistant to penicillin G, 40 5 % to ampicillin (MIC>0-16 .tg/ml), 46% to amoxycillin, and 47'5 % to carbenicillin. For cephalexin and cephaloridine, 25 % and 8 5 % respectively of all strains were relatively resistant (MIC > 3 12 jig/ml). For cefazolin all MICs fell into a range of 0 097-3 12 jig/ml. Resistance to tetracycline, doxycycline, minocycine, erythromycin, and spiramycin (MIC > I g/ml) was found in 9-5 %,7 %, 6 %, 36 5 %, and 71 % respectively of all isolates. No strains were resistant to rifampicin. For chloramphenicol and thiamphenicol the MICs ranged from 0 39 to 12-5 ,ug/ml and from 0-195 to 3-12 jig/ml respectively. The results for sulphamethoxazole, trimethoprim, and the combination of sulphamethoxazole and trimethoprim in a 20:1 ratio are given and discussed. The fractional inhibitory concentration (FIC) indices have also been calculated. No ,-lactamase-producing strains were found, and a contingency coefficient C has been determined for all the pairs of antibiotics investigated.
Sexually Transmitted Infections, 2004
Objectives: Decreasing susceptibility of Neisseria gonorrhoeae to fluoroquinolones has been reported in several countries. Knowledge of local N gonorrhoeae susceptibilities to various antimicrobials is important for establishing a rational treatment strategy in each region. Methods: Isolates of N gonorrhoeae from male urethritis patients attending four urological clinics in Hyogo and Osaka prefectures in Japan were collected during 2002. The MICs for nine antimicrobials: penicillin G, tetracycline, cefixime, ceftriaxone, levofloxacin, gatifloxacin, ciprofloxacin, moxifloxacin, and spectinomycin were determined for each isolate. All isolates were also tested for b lactamase producing profiles. Results: Among the 87 isolates obtained, only one isolate was revealed to produce b lactamase. MIC 90 values for ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin were over 8 mg/ml, over 8 mg/ml, 4 mg/ml, and 2 mg/ml, respectively. The proportion of isolates resistant to fluoroquinolones was over 60% (ciprofloxacin, 70.1%; levofloxacin, 65.5%; gatifloxacin, 70.1%). Chromosomally mediated penicillin and tetracycline resistance was identified in 12.6% and 33.3% of the isolates. MIC 90 values for cefixime and ceftriaxone and were 0.5 mg/ml and 0.0063 mg/ml. All isolates were sensitive to ceftriaxone and 90.8% of them were sensitive to cefixime. MIC 90 for spectinomycin was 32 mg/ml and all isolates were sensitive to it. Fluoroquinolone resistance correlated significantly with MICs for penicillin G but not tetracycline.
ANTIMICROBIAL RESISTANCE IN NEISSERIA GONORRHOEAE
Emergency and spread of drug resistance in Neisseria gonorrhoeae is a global concern. This study evaluated the prevalence of antimicrobial resistance in Neisseria gonorrhoeae over the months of March-June at Mzuzu health center (Mapale). Antimicrobial susceptibility testing were performed and interpreted according to Clinical Laboratory Standards Institute (CLSI) criteria using the disk diffusion methodology against erythromycin, ciprofloxacin, tetracycline and ceftriaxone. During the study period significant increase in combined resistance to tetracycline and ceftriaxone was observed. The resistance rate during the study period was also observed to be high in tetracycline.
Infection and Drug Resistance, 2020
The study aimed to evaluate meropenem, fosfomycin, berberine hydrochloride, and doxycycline minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae collected from eight provinces in China in 2018. Methods: The MICs of 540 Neisseria gonorrhoeae isolates (451 isolates selected randomly and 89 isolates selected with preference) were determined to meropenem, fosfomycin, berberine hydrochloride, and doxycycline using the agar dilution method, and the MICs of ceftriaxone and azithromycin were detected for comparison. Results: Among 451 randomly selected isolates, the MIC 90 was 0.06 mg/L for meropenem, 64 mg/L for fosfomycin, 64 mg/L for berberine hydrochloride, and 16 mg/L for doxycycline. All isolates showed the MIC ≤ 0.125 mg/L to meropenem, 13 isolates (2.9%) showed MIC > 64 mg/L to fosfomycin, 8 isolates (1.8%) demonstrated MIC > 64 mg/L to berberine hydrochloride, and 271 isolates (60.1%) demonstrated MIC > 1 mg/L to doxycycline. Comparing all 540 tested isolates, a correlation of r = 0.50 (P < 0.001) between meropenem and ceftriaxone MIC was observed. In 24 ceftriaxone-decreased susceptibility isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 1 isolate (4.2%) showed an MIC > 64 mg/L for fosfomycin, 1 isolate (4.2%) showed an MIC > 64 mg/L for berberine hydrochloride, and 13 isolates (54.2%) showed an MIC > 1 mg/L for doxycycline. In 87 azithromycin resistant isolates, all isolates showed an MIC ≤ 0.125 mg/L for meropenem, 2 isolates (2.3%) showed an MIC > 64 mg/L for fosfomycin, 4 isolates (4.6%) showed an MIC > 64 mg/L for berberine hydrochloride, and 64 isolates (73.6%) showed an MIC > 1 mg/L for doxycycline. Conclusion: The in vitro results suggest that meropenem might be a promising treatment option for resistant gonococcal infections, while the effects of fosfomycin and berberine hydrochloride should be further evaluated as potential therapeutic agents. The effectiveness of these drugs in animal experiments and clinical use may need further study.
The Journal of antimicrobial chemotherapy, 2015
New antimicrobials are essential to prevent gonorrhoea becoming an untreatable infection. Herein, the in vitro activities of the novel bicyclolides modithromycin (EDP-420, EP-013420, S-013420) and EDP-322 against Neisseria gonorrhoeae strains were investigated and compared with antimicrobials currently or previously recommended for treatment of gonorrhoea. MICs (mg/L) were determined using an agar dilution method (modithromycin and EDP-322) or Etest (seven antimicrobials) for a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates (n = 225) and international reference strains (n = 29), including diverse MDR and XDR isolates. The MIC range, modal MIC, MIC50 and MIC90 of modithromycin and EDP-322 were 0.004-256, 0.25, 0.25 and 1 mg/L and 0.008-16, 0.5, 0.5 and 1 mg/L, respectively. The activities of modithromycin and EDP-322 were mainly superior to those of azithromycin and additional antimicrobials investigated. In general, there was ...
2006
Methods: Antimicrobial susceptibilities of all gonococcal isolates received by the Greek National Reference Center for N. gonorrhoeae during the study period were determined in terms of MICs using Etest. Trends in yearly isolation frequencies by susceptibility category were estimated for defining significant changes in overall susceptibility figures. Results: Cefotaxime and spectinomycin retained undiminished activity against all isolates throughout the study period. High rates of resistance and intermediate susceptibilities were noticed for penicillin, tetracycline and erythromycin, and even for norfloxacin and ciprofloxacin. A substantial portion (16.5%) of the gonococcal samples consisted of multiresistant strains exhibiting resistance to two or more agents of different antibiotic classes. Although annual rates of low-level chromosomal resistance decreased, high-level resistance owing to the presence of penicillin-and tetracycline-resistance plasmids increased. Fluoroquinolone resistance also showed a significant increasing trend after 1996, reaching a peak rate of 11.3% in 2004. Conclusion: Third-generation cephalosporins and spectinomycin should be considered as first-choice drugs for the empirical treatment of gonorrhoea in Greece.