Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil, 1998

BACKGROUND: The identification of Neisseria gonorrhoeae isolates resistant to antimicrobial agents currently recommended for the treatment of gonococcal infections continues to escalate globally. Thus, in some areas, resistance to fluoroquinolone drugs is commonplace; several reports document resistance to third-generation cephalosporins, and the sporadic isolation of spectinomycin-resistant isolates continues unabated. Gonococcal resistance to azithromycin, an antibiotic used for the primary treatment of gonococcal infections in some Latin American countries, also has been described. Because the prevalence of resistant isolates is insufficiently documented in many areas of Latin America, the efficacy of locally recommended therapies for gonococcal infections is often unknown. GOAL: To determine the antimicrobial susceptibility and strain types of N gonorrhoeae isolates collected in Manaus, Brazil. These data will establish antimicrobial susceptibility baseline data for the region as a reference point for future surveillance. STUDY DESIGN: Consecutive N gonorrhoeae isolates from urethral and endocervical specimens were collected and examined for identity, antimicrobial susceptibility, and strain type (plasmid content, tetM type, auxotype, and serovar). RESULTS: Most of the isolates (65/81; 85.2%) were resistant to tetracycline, penicillin, or both, with the majority (n = 62) carrying plasmid-mediated resistance to tetracycline (tetracycline-resistant N gonorrhoeae [TRNG]). All of the TRNG contained the Dutch-type tetM plasmid, and 18 were A/S class NR/IA-02. Penicillinase-producing N gonorrhoeae comprised 8.2% (7/81) of the isolates. Of these seven isolates, four also were TRNG, and two carried chromosomal resistance to tetracycline. The isolates were susceptible to ciprofloxacin, spectinomycin, and ceftriaxone. However, 23 isolates were characterized by reduced susceptibility to azithromycin (MIC, 0.25-0.5 microg/ml), and one isolate had reduced susceptibility to ciprofloxacin (MIC, 0.25 microg/ml). CONCLUSIONS: This study supports the continued use of third-generation cephalosporins, spectinomycin, and fluoroquinolone drugs for the primary treatment of gonococcal infections in Manaus. The occurrence of isolates with reduced susceptibility to azithromycin and ciprofloxacin underscores the importance of ongoing antimicrobial susceptibility monitoring to support decisions regarding appropriate drugs for the treatment of gonococcal infections.     

南京地区1999-2006年淋球菌青霉素耐药性及耐药质粒基因型研究

目的了解南京地区淋球菌青霉素耐药状况及产青霉素酶淋球菌的质粒基因型的流行情况。方法采用琼脂稀释法检测淋球菌对青霉素的最小抑菌浓度采用纸片酸度定量法检测菌株是否产青霉素酶。采用单管PCR方法对产青霉素酶淋球菌耐药质粒进行基因分型。结果8年间共检测1208株淋球菌，青霉素总耐药率为84．02％（1015／1208）。非产青霉素酶淋球菌中，染色体介导的耐青霉素淋球菌占74．02％（550/743）。产青霉素酶淋球菌占38．49％（465／1208），其中177（38．06％）株同时为质粒介导的耐四环素淋球菌即质粒介导的高度耐四环素淋球菌。产青霉素酶淋球菌阳性率自1999（8．04％）年起逐年增加，至2004年达最高（57．36％），2005、2006年略有下降。质粒PCR分型显示，所测菌株均携带亚洲型质粒。结论南京地区耐青霉素淋球菌始终维持在较高水平，产青霉素酶淋球菌近年增加较快，携带亚洲型质粒的产青霉素酶淋球菌在南京地区流行，未发现其他类型的质粒。     

In vitro susceptibility of Neisseria gonorrhoeae to cefuroxime, penicillin, and tetracycline in Denmark-1979

In vitro susceptibility to cefuroxime, penicillin, and tetracycline of 963 strains of Neisseria gonorrhoeae strains isolated in Denmark in 1979 was tested. If penicillinase-producing strains of N. gonorrhoeae were excluded from the analysis, a significant positive correlation between the 50% inhibitory concentrations (IC50) of cefuroxime and penicillin was observed (r = 0.87). Among strains exhibiting IC50 of penicillin of greater than or equal to 0.30 microgram/ml, 80% (106/133) had an IC50 of cefuroxime of greater than or equal to 0.088. Ninety-six per cent (106/110) of strains exhibiting an IC50 of cefuroxime of greater than or equal to 0.088 microgram/ml were less susceptible to penicillin (IC50, greater than or equal to 0.30 microgram/ml). The IC50 values of tetracycline were positively correlated with those of cefuroxime. There was no apparent difference between the level of antimicrobial susceptibility of strains (623) isolated from urogenital sites and that of strains (109) from the pharynx.     

Surveillance of antibiotic resistance of Neisseria gonorrhoeae isolates in China, 1993-1998

BACKGROUND: The prevalence of sexually transmitted diseases (STDs) has been increasing in China since the 1980s. Because gonorrhea is the most frequently reported STD there, information on the antimicrobial susceptibility of Neisseria gonorrhoeae will aid in its control. GOAL: To investigate the antimicrobial susceptibility of N gonorrhoeae isolates in China and to provide data for formulation of treatment guidelines and control policies. METHODS: The agar dilution technique was used to determine antimicrobial susceptibility, and acidimetric method was used to test for penicillinase-producing N gonorrhoeae. RESULTS: A total of 3186 gonococcal isolates were tested during the 6-year study period. The rate of resistance to penicillin was 66.70%; 8.14% of isolates were penicillinase-producing N gonorrhoeae. The percentage of tetracycline-resistant isolates was 92.03%, and that of highly tetracycline-resistant isolates was 4.65%. The rate of resistance to ciprofloxacin was also relatively high (34.25%). The rates of resistance to spectinomycin and ceftriaxone were 0.44% and 0.57%. CONCLUSIONS: The gonococcal isolates in China are relatively highly resistant to penicillin, tetracycline, and ciprofloxacin, but most of them are still susceptible to spectinomycin and ceftriaxone. Standardized treatment of gonorrhea is needed to prevent further spread of resistant gonococcal strains.     

淋病奈瑟菌对头孢曲松耐药性及敏感性降低机制的研究进展

头孢曲松为目前治疗淋病的首选药物之一,国内外淋球菌耐药监测均发现淋球菌对头孢曲松敏感性降低,并已发现少数散发的头孢曲松耐药株。淋球菌对头孢曲松敏感性降低主要由染色体介导,目前大多数研究主要关注三个方面：一是抗生素作用靶位点的改变,影响抗生素与淋球菌的结合产生耐药;二是细菌细胞膜孔蛋白的改变,导致膜通透性降低产生耐药;三是外排系统的改变,导致细菌外排作用增强产生耐药。涉及的基因有penA、ponA、porB和mtrR等。     

Antimicrobial susceptibility of Neisseria gonorrhoeae in Cuba (1995-1999): implications for treatment of gonorrhea

BACKGROUND: Antibiotic-resistant strains of Neisseria gonorrhoeae, especially those resistant to penicillin and tetracycline, have spread with remarkable rapidity in many Caribbean countries. GOAL: The goal of the study was to survey the antibiotic susceptibilities of N gonorrhoeae strains isolated from 1995 to 1999 in Cuba and to discuss the impact of antimicrobial resistance on the management of gonorrhea in the country. STUDY DESIGN: Susceptibility of the strains to penicillin, tetracycline, cefuroxime, ceftriaxone, ciprofloxacin, spectinomycin, and azithromycin were determined by an agar dilution method. RESULTS: Penicillin and tetracycline resistance was noted in 60.8% and 54.2%, respectively, of the N gonorrhoeae strains tested. A total of 63.35 (76/120) of the N gonorrhoeae strains exhibited plasmid-mediated resistance to penicillin, tetracycline, or both. Strains with chromosomally mediated resistance to these antibiotics accounted for 10% (12/120) of the strains. The strains were susceptible to ceftriaxone, cefuroxime, spectinomycin, and ciprofloxacin. One strain's ciprofloxacin MIC was 0.125 mircog/ml. Of the 52 strains tested, 23.1% displayed intermediate resistance to azithromycin. CONCLUSIONS: N gonorrhoeae strains exhibited a high frequency of resistance and multiresistance to penicillin and tetracycline. Therefore, these antibiotics should no longer be used to treat gonococcal infections in Cuba and should be substituted with effective drugs such as third-generation cephalosporins, spectinomycin, and fluoroquinolones. The detection of intermediate resistance to azithromycin and ciprofloxacin underlines the importance of periodic surveillance for susceptibility of N gonorrhoeae strains to antimicrobials agents used as primary therapy for gonorrhea.     

Association of auxotypes of Neisseria gonorrhoeae and susceptibility to penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam

Isolates of Neisseria gonorrhoeae from 304 patients attending a venereal disease clinic were examined by a plate dilution method for their susceptibility to six antibiotics: penicillin G, spectinomycin, tetracycline, cefaclor, cefoxitin, and moxalactam. The isolates were also characterized by gonococcal auxotyping. The most frequent auxotypes were Nonrequiring, 58%; Pro-, 14%; Pro- Arg (Orn*) Ura-, 14%; Arg- Hyx- Ura-, 6%; and a miscellaneous group consisting of 8% of the isolates. If the entire group of isolates were examined, moxalactam was the most active of the antibiotics; 94% of the isolates were inhibited by less than or equal to 0.25 microgram/ml. The Pro- Arg (Orn*) Ura- isolates were relatively resistant to penicillin G and cefoxitin. The Arg- Hyx- Ura- group of isolates was the most susceptible of the auxotypes to all of the antibiotics except spectinomycin. The uncommon auxotype Arg (Orn*) Ura- has a requirement for arginine that is satisfied by citrulline but not by ornithine. The results of the present study indicate that the nutritional requirements of gonococci may be associated with their response to certain antibiotics.     

High prevalence of Neisseria gonorrhoeae strains with reduced susceptibility to fluoroquinolones in Japan.

OBJECTIVE--To study the antibiotic susceptibility of Neisseria gonorrhoeae strains isolated in Japan and, in particular, to examine the possibility of emerging fluoroquinolone resistance. MATERIALS AND METHODS--Sixty-nine strains of Neisseria gonorrhoeae isolated in 1992 were tested for susceptibility to 15 antibiotics including fluoroquinolones and were seroclassified. Twenty-seven strains isolated from 1981 to 1984 were also evaluated as controls. RESULTS--The MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the isolates from 1992 were 2.0, 1.0, and 0.5 microgram/ml, respectively. The MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the isolates from 1981-84 (controls) were 0.25, 0.125, and 0.063 microgram/ml, respectively. These results indicate that the MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the strains from 1992 were 8-fold higher than those against the strains from 1981-84. However, there were no significant differences in susceptibility to beta-lactams, tetracyclines, macrolides, and spectinomycin between the isolates from 1992 and those from 1981-84. The majority of the isolates belonged to the WII/WIII serogroup. There was no relationship between fluoroquinolone resistance and serogroup. CONCLUSIONS--Fluoroquinolones have been used frequently as first-line therapy and have provided excellent clinical efficacy for gonococcal infections for the last several years in Japan. However, our data indicate that a rapid decrease in the susceptibility of Neisseria gonorrhoeae to fluoroquinolones is occurring in our country.     

Antimicrobial susceptibility of Neisseria gonorrhoeae in Zaire: high level plasmid-mediated tetracycline resistance in central Africa.

OBJECTIVE--To determine the in vitro antimicrobial susceptibility of gonococcal strains isolated in 1988 among female prostitutes in Kinshasa, Zaire and to characterise strains with high level tetracycline resistance. METHODS--Minimal inhibitory concentrations of 8 antimicrobials were measured by agar dilution technique. Plasmid-profiles and serovars were determined. RESULTS--Two hundred and thirteen strains of Neisseria gonorrhoeae were tested of which 59% were beta-lactamase producers and an additional 21% showed intermediate or chromosomal resistance to penicillin (MIC = 0.5-8 mg/l). Eleven percent of the strains were resistant to the combination sulfamethoxazole-trimethoprim (MIC greater than 8 mg/l) and 57% of the isolates showed decreased susceptibility to thiamphenicol (MIC = 1-4 mg/l). All strains were sensitive to spectinomycin, norfloxacin and ceftriaxone and moderately sensitive to kanamycin. Chromosomal resistance to tetracycline was observed in 45% of strains (MIC = 2-8 mg/l). Ten percent were highly resistant to tetracycline (TRNG, MIC = 16-128 mg/l) and were shown to carry a plasmid borne Tet M determinant; such strains were not found in Kinshasa in 1985. TRNG belonged to 4 different serovars, which were also the dominant serovars in non-TRNG. CONCLUSION--These findings illustrate the high frequency of multiresistant gonococci in Zaire and suggest that high level tetracycline resistant strains of N. gonorrhoeae have become endemic in Central Africa.     

头孢曲松低敏的淋球菌中青霉素结合蛋白2氨基酸替代或插入模式研究

目的 检测头孢曲松低敏的淋球菌中青霉素结合蛋白2（PBP2）模式,探讨其是否与淋球菌对头孢曲松敏感性降低有关。方法 将11株头孢曲松低敏和2株头孢曲松敏感的淋球菌penA基因全基因测序,通过BLASTn与BLASTx分析,研究penA基因的碱基插入和置换情况及PBP2中氨基酸插入和置换模式。结果 13株淋球菌的penA基因中有多个碱基置换或插入,PBP2中共发现5种模式的氨基酸插入或置换模式,没有发现PBP2镶嵌状结构模式。结论 PBP2的镶嵌状结构可能不是导致淋球菌对头孢曲松敏感性下降的主要因素。     

Molecular epidemiology of Neisseria gonorrhoeae exhibiting decreased susceptibility and resistance to ciprofloxacin in Hawaii, 1991-1999

BACKGROUND: Clinically significant resistance to Centers for Disease Control and Prevention (CDC)-recommended doses of fluoroquinolones (ciprofloxacin and ofloxacin) has been reported for Neisseria gonorrhoeae. In Hawaii, fluoroquinolone-resistant gonococcal isolates were first identified in 1991. GOAL: To assess the diversity, based on phenotypic and genotypic characterization, of gonococcal isolates exhibiting decreased susceptibility (CipI; MICs = 0.125-0.5 microg/ml) or clinically significant resistance (CipR; MICs > or = 1 microg/ml) to ciprofloxacin in Hawaii from 1991 through 1999. STUDY DESIGN: Antimicrobial susceptibilities, auxotype/serovar (A/S) class, GyrA/ParC alteration patterns, and plasmid profiles were determined for gonococci isolated in Honolulu from 1991 through 1999 that exhibited intermediate or clinically significant resistance to ciprofloxacin. Strain phenotypes were defined by A/S class, GyrA/ParC alteration pattern, and penicillin-tetracycline resistance phenotype supplemented with plasmid profiles for beta-lactamase-producing isolates. RESULTS: Altogether, 68 isolates exhibiting intermediate or clinically significant resistance to ciprofloxacin belonged to 23 and 19 strain phenotypes, respectively. Among the CipI and CipR isolates, 4 and 13 GyrA/ParC alterations patterns were identified, respectively. The 91,95/Asp-86 alteration pattern occurred most frequently among CipR isolates. Forty-four strain phenotypes were represented by only one isolate. In addition, seven pairs and two clusters of isolates were identified. CONCLUSIONS: From 1991 through 1997, few gonococcal strains exhibiting intermediate or clinically significant resistance to CDC-recommended doses of fluoroquinolones were identified from Hawaii. Isolates belonged to a large number of phenotypic and genotypic types, suggesting that most cases were imported, with only a few instances in which isolate pairs indicated that secondary transmission of infections had occurred in Hawaii. Beginning in 1998, the number of CipR isolates increased markedly, and more isolates belonged to fewer phenotypic and genotypic types, suggesting either more frequent importation of fewer strain types or the possibility that the endemic spread of a few strains is beginning to occur.     

Antibiotic susceptibility in relation to serogroup and auxotype of Neisseria gonorrhoeae isolates from Gabon

We tested 75 beta-lactamase-positive (penicillinase-producing Neisseria gonorrhoeae; PPNG) and 147 beta-lactamase negative (non-PPNG) strains of N. gonorrhoeae obtained during a two-year period in Franceville, a semirural community in southeastern Gabon, for susceptibility to antimicrobial agents, auxotype, and serotype. The most common auxotypes were the nonrequiring and proline-requiring strains. Of the non-PPNG strains tested, 37% belonged to serogroup WI, 48% to serogroup WII, and 15% could not be grouped with commercially available antisera. Except for four strains that belonged to serogroup WII, the PPNG strains were classified as serogroup WI or ungroupable. We determined the concentrations at which 90% of strains were inhibited (MIC90) for spectinomycin (32 mg/liter for both PPNG and non-PPNG), kanamycin (32 mg/liter for both PPNG and non-PPNG), tetracycline (2 mg/liter for non-PPNG, 1 mg/liter for PPNG), cefotaxime (0.03 mg/liter for non-PPNG, 0.008 mg/liter for PPNG), and penicillin (1 mg/liter for non-PPNG, greater than 32 mg/liter for PPNG). A MIC of greater than or equal to 2 mg of tetracycline/liter was noted for 17% of the strains. Strains belonging to serogroup WII were more resistant to tetracycline and cefotaxime than other strains. Proline-requiring strains were less susceptible to tetracycline, cefotaxime, and spectinomycin than the nonrequiring strains. The decreased sensitivity to penicillin (non-PPNG strains) and tetracycline was determined by proline-requiring strains belonging to serogroup WII.