Nutritional requirements and penicillin susceptibilities of gonococci from pharyngeal and anogenital sites.

Neisseria gonorrhoeae was isolated from 5.9% of oropharyngeal specimens obtained from patients attending a clinic for sexually transmitted diseases. Oropharyngeal isolates from 69 patients and anogenital isolated from 97 other patients attending the same clinic were compared. Many of the gonococci could be differentiated by the compounds required for growth in chemically defined media or by differences in the minimum inhibitory concentration (MIC) of penicillin G. Strains with requirements for either proline (Pro-) or arginine (Arg-) or for none of the compounds that are used for differentiation (zero phenotype) were more common in the oropharynx (91.3% of patients) than in anogenital sites (73.2% of patients). On the other hand, gonococci with multiple requirements that include arginine, hypoxanthine, and uracil (AHU strains) were present in oropharyngeal specimens from only three patients (4.4%), but were isolated from anogenital specimens from 18 patients (18.6%). A high susceptibility to penicillin characterised the AHU strains from all sites, as others have reported. The penicillin MIC ranged from 0.003-0.72 microgram/ml for strains with Pro-, Arg-, and zero phenotypes. However, a penicillin MIC greater than or equal to 0.42 microgram/ml was found for 17.6% of oropharyngeal isolates of these types, but for only 4.1% of Pro-, Arg-, and zero isolates from anogenital sites. None of these moderately resistant strains produced beta-lactamase. Our findings indicate that gonococci differ in their ability to colonise the oropharynx successfully.     

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.     

Changes in the prevalence of auxotypes of Neisseria gonorrhoeae among black and white patients attending a clinic for sexually transmitted diseases

Before 1978, isolates of Neisseria gonorrhoeae from white patients attending a venereal disease clinic were more susceptible to penicillin G than were isolates from black patients, because the whites were more frequently infected with the Arg- Hyx- Ura- auxotype that was highly susceptible to penicillin. Recent isolates from the same clinic show a change both in the auxotypes and in the penicillin susceptibility of N. gonorrhoeae infecting the two patient groups. Of 211 isolates studied in 1978, the four most common auxotypes were, in decreasing frequency: Pro-, nonrequiring, Arg- Hyx- Ura- and Arg-. In the present study of 265 isolates, the order of frequency was nonrequiring; Pro-; Pro- Arg-(Orn*) Ura-; and Arg- Hyx- Ura-. The Pro- Arg-(Orn*) Ura- auxotype was new to the clinic and was significantly more frequent in white than in black patients and significantly more resistant to penicillin than were gonococci of the remaining auxotypes. With the appearance of the Pro- Arg-(Orn*) Ura- auxotype among white patients, there was no significant difference in the susceptibility to penicillin of isolates of N. gonorrhoeae from the two groups of patients.     

Characteristics of Neisseria gonorrhoeae strains isolated on selective and nonselective media

The possible inhibition of Neisseria gonorrhoeae on modified Thayer-Martin (VCNT) medium was investigated by inoculation of multiple media with specimens from 3,490 patients. N. gonorrhoeae was recovered from 461 patients, and in 24 cases (5.2%) it was isolated on drug-free medium only; 18% of the recoveries were on VCNT medium only. The minimal inhibitory concentration (MIC) of benzylpenicillin was determined for 411 of the strains, and 175 were examined for responses to 12 other antibiotics and for auxotype. Of the 24 strains isolated on drug-free medium only, one was inhibited by trimethoprim at a concentration of 2.0 micrograms/ml and four others had MICs of vancomycin of less than or equal to 2.0 micrograms/ml. The remainder were resistant to vancomycin, trimethoprim, and colistin at the concentrations present in VCNT medium. Unexpectedly, four strains isolated on both VCNT and drug-free medium had MICs of vancomycin of less than or equal to 3.0 micrograms/ml and were defined as hypersusceptible. Genetic tests showed that gonococci resistant to less than or equal to 0.5 microgram of vancomycin/ml differed genotypically from those resistant to 1.0 microgram/ml. The eight strains hypersusceptible to vancomycin were highly susceptible to various other antibiotics. Their nutritional requirements included hypoxanthine (Hyx-) and uracil (Ura-), and all but one also required arginine (Arg-), which for two strains could not be replaced by ornithine (Arg0-). Pro-,Arg0-,Ura- (5.7%) and Arg0-,Ura- (1.1%) auxotypes were found at this time but not in earlier studies of gonococci isolated in the same clinic.     

Susceptibility of different auxotypes of Neisseria gonorrhoeae to norfloxacin, cefotaxime, cefuroxime, and erythromycin

Isolates of Neisseria gonorrhoeae from 150 patients attending a venereal disease clinic were examined for their susceptibility to four antibiotics (norfloxacin, cefotaxime, cefuroxime, and erythromycin) by a plate-dilution method. The isolates were also characterized by gonococcal auxotyping. The most frequent auxotypes were nonrequiring, 50%; Pro-, 16.7%; Pro-, Arg-, (Orn*), Ura-, 10.7%; Arg-, Hyx-, Ura-, 12.7%; and a miscellaneous group consisting of 10% of the isolates. Norfloxacin was the most active of the antibiotics; all of the isolates were inhibited by less than or equal to 0.06 microgram/ml. The Arg-, Hyx-, Ura- group of isolates was the most susceptible of the auxotypes to antibiotics. In the present study N. gonorrhoeae of the Arg-, Hyx-, Ura- auxotype fell into two groups with respect to erythromycin, one highly susceptible and one less susceptible. The results of the present study provide further evidence that the nutritional requirements of gonococci are associated with their response to certain antibiotics.     

Serogrouping of Neisseria gonorrhoeae: correlation of serogroup with disseminated gonococcal infection

Gonococci can be divided into serogroups WI, WII, and WIII by coagglutination. To assess the clinical correlation of serogroups of gonococci, we studied isolates of gonococci from patients with disseminated and uncomplicated gonococcal infections in three cities in the United States. Strains of Neisseria gonorrhoeae belonging to serogroup WI represented 85 (84%) of 101 isolates from patients with disseminated gonococcal infection (DGI) and 68 (40%) of 168 isolates from patients with uncomplicated gonorrhea (P less than .001). The auxotype Arg-, Hyx-, Ura- (AHU) represented 62 (61%) of 101 isolates from DGI and 54 (32%) of 168 isolates from uncomplicated infection (p less than .001); all AHU isolates were serogroup WI. Among other auxotypes, WI strains represented 25 (64%) of 39 isolates from patients with DGI and 14 (12%) of 114 from uncomplicated infections (P less than .001). In Atlanta only, 13 (34%) of 38 isolates from DGI were AHU, but 31 (82%) were serogroup WI (P less than .001). Thus gonococci of serogroup WI are associated with DGI in these cities of the United States, and this correlation appears to be independent of auxotype. Serogroup WI is correlated with serum resistance.     

Antibiotic susceptibilities, serotypes and auxotypes of Neisseria gonorrhoeae isolated in New Zealand.

OBJECTIVE--The aim of the study was to determine the distribution of auxotypes and serotypes and the prevalence of antibiotic resistance among New Zealand isolates of Neisseria gonorrhoeae. MATERIALS AND METHODS--A total of 486 gonococci isolated in 1988 were auxotyped, serotyped, and tested for susceptibilities to ten antibiotics. RESULTS--The gonococci were susceptible to all the antibiotics tested except penicillin and tetracycline. Eleven (2.2%) produced beta-lactamase, one (0.2%) showed chromosomal penicillin resistance, and 18 (3.7%) were resistant to a low-level of tetracycline. Most of the gonococci belonged to six auxotypes. The three predominant auxotypes were arginine-requiring (Arg-), non-requiring (NR), and arginine, hypoxanthine, uracil-requiring (AHU-). The majority of the isolates belonged to serogroup IB and to six serovars. The most prevalent serovars were IB-3 and IB-1. There was an association between penicillin susceptibility and auxotype or serovar among non-penicillinase producing N. gonorrhoeae (PPNG) isolates. CONCLUSIONS--Antibiotic resistance, including penicillin resistance, remains uncommon among gonococci in New Zealand. Baselines have been established for future epidemiological studies using both auxotyping and serotyping.     

Epidemiology of penicillin resistant Neisseria gonorrhoeae.

OBJECTIVE--To study the epidemiology of Neisseria gonorrhoeae that exhibit both chromosomal and plasmid-mediated resistance to penicillin. MATERIALS AND METHODS--A total of 1589 strains of N gonorrhoeae isolated from patients attending St Mary's Hospital, London were tested for both their susceptibility to penicillin and for their auxotype and serotype. RESULTS--Of the 940 non-penicillinase producing N gonorrhoeae, 840 were considered penicillin sensitive (MIC less than or equal to 0.5 mg/l) and 100 were chromosomally-mediated resistant N gonorrhoeae (CMRNG), (MIC greater than or equal to 1.0 mg/l). Of the 649 penicillinase producing N gonorrhoeae (PPNG), 429 carried the 4.4 megadalton (MDa) penicillinase encoding plasmid and 220 carried the 3.2 MDa plasmid. CMRNG were predominantly serogroup IB (90%). PPNG with 3.2 MDa plasmid were the only group more often serogroup IA (58%) than IB (42%). Serovar IA-1/2 and requirement for arginine, hypoxanthine and uracil (AHU) were associated with increased susceptibility to penicillin whereas serovar IB-5/7 was associated with decreased susceptibility in nonPPNG. There was a significant difference in the distribution of the IA and IB serovars between PPNG carrying either the 4.4 MDa or 3.2 MDa plasmid. AHU and PAOU requiring strains were not found among PPNG and were uncommon among CMRNG. CONCLUSION--Some clear associations have been found but the pattern among PPNG appears more complex and in most instances could be related to clusters of a single strain over a short time span.     

Incidence of disseminated gonococcal infection correlated with the presence of AHU auxotype of Neisseria gonorrhoeae in a community

Strains of Neisseria gonorrhoeae requiring arginine, hypoxanthine, and uracil (AHU) may cause disseminated gonococcal infection (DGI). A significant epidemiologic association was noted between the incidence of disseminated gonococcal infection and the presence of gonococci of the AHU auxotype in the community over a nine-year period. Thirty-nine patients with DGI were identified from hospital records of January 1974-December 1982. During this interval, gonococcal isolates from patients in the community were collected at a venereal disease clinic and a hospital emergency room. The incidence of patients hospitalized for DGI dropped significantly after 1978. The year of highest incidence of DGI was 1977, when there were 429 cases of DGI per 100,000 cases of uncomplicated gonorrhea; the incidence of gonococcal isolates of the AHU auxotype in that year was 26.3%. In contrast, this auxotype accounted for only 4.6% of gonococcal isolates in 1980, when the incidence of DGI had decreased to 58 cases per 100,000 cases of uncomplicated gonorrhea. When DGI and gonococci of the AHU auxotype from the community were ranked for incidence by year, a significant correlation between the two was found (P less than .001). Thus the incidence of patients with DGI in the hospital reflected the presence of gonococci of the AHU auxotype in the community.     

Auxotypes and antibiotic susceptibilities of Neisseria gonorrhoeae from women with acute salpingitis. Comparison with gonococci causing uncomplicated genital tract infections in women

An investigation of the MICs of various antibiotics and the nutritional requirements (auxotypes) of Neisseria gonorrhoeae recovered from the cervix, fallopian tubes, and peritoneal cavity of women with acute salpingitis was done. These MICs and auxotypes were compared to those of gonococci isolated from the cervix of women with uncomplicated or asymptomatic genital tract gonorrhea. The MICs of minocycline, penicillin G, ampicillin, cefoxitin, and cefaclor for gonococci isolated from women with acute salpingitis were significantly higher. Significant differences in auxotype patterns were identified between isolates from salpingitis cases and uncomplicated cases. The prototrophic form was the most common (75%) among salpingitis strains. No strains requiring arginine, hypoxanthine, and uracil were identified among the salpingitis isolates. In contrast, strains that required these nutrients were the most frequent auxotype among isolated from women with uncomplicated genital tract gonorrhea. Discriminant analysis revealed that the MIC of minocycline and the auxotype were the most powerful discriminators between groups of patients with different manifestations of gonorrhea.     

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 microgram/ml) were relatively resistant to penicillin G (MIC greater than or equal to 0.08 microgram/ml). About 51% of all strains were relatively resistant to penicillin G, 40.5% to ampicillin (MIC greater than or equal to 0.16 microgram/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 greater than 3.12 microgram/ml). For cefazolin all MICs fell into a range of 0.097--3.12 microgram/ml. Resistance to tetracycline, doxycycline, minocycline, erythromycin, and spiramycin (MIC greater than or equal to 1 microgram/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 microgram/ml and from 0.195 to 3.12 microgram/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 beta-lactamase-producing strains were found, and a contingency coefficient C has been determined for all the pairs of antibiotics investigated.     

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 microgram/ml) were relatively resistant to penicillin G (MIC greater than or equal to 0.08 microgram/ml). About 51% of all strains were relatively resistant to penicillin G, 40.5% to ampicillin (MIC greater than or equal to 0.16 microgram/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 greater than 3.12 microgram/ml). For cefazolin all MICs fell into a range of 0.097--3.12 microgram/ml. Resistance to tetracycline, doxycycline, minocycline, erythromycin, and spiramycin (MIC greater than or equal to 1 microgram/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 microgram/ml and from 0.195 to 3.12 microgram/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 beta-lactamase-producing strains were found, and a contingency coefficient C has been determined for all the pairs of antibiotics investigated.     

Susceptibility of Trichomonas vaginalis strains to metronidazole: response to treatment

The effect of the susceptibility of Trichomonas vaginalis strains to metronidazole on response to treatment was determined from minimal inhibitory concentrations (MICs) for organisms isolated during a clinical trial in which single 1- and 2-g doses of metronidazole were compared. Fifty-seven strains were isolated from patients receiving 1 g of metronidazole, and 75 from those receiving 2 g. The mean MIC for all strains was 1.50 microgram/ml (range, 0.5-4.5 microgram/ml) and was similar in both groups. The mean MICs for isolates from patients who were cured were significantly less than the mean MICs of isolates from those who were treatment failures. The cure rates, compared to the MICs for the strains isolated, varied from 84% (MIC, 0.5 microgram/ml) to 16% (MIC, greater than or equal to 3.0 microgram/ml) for the group given the single 1-g dose and from 94% (MIC, 0.5 microgram/ml) to 43% (MIC, greater than or equal to 3.0 micrograms/ml) for those given the 2-g dose. The data demonstrate a direct relationship between susceptibility of T. vaginalis isolates and response to treatment with single-dose regimens of metronidazole.     

Sensitivity of Neisseria gonorrhoeae to antibiotics in London (1976-78).

Three surveys of the sensitivity of pretreatment isolates of gonococci to penicillin, ampicillin, tetracycline, spectinomycin, streptomycin, and co-trimoxazole were carried out during the period 1976-78. Compared with the results of previous surveys in the London area the decline in the proportion of strains of gonococci which are insensitive to penicillin appears to have halted. No changes were found in the levels of resistance to ampicillin, tetracycline, or spectinomycin during the period surveyed, although there was a slight increase in the proportion of strains requiring concentrations of 20 microgram spectinomycin per ml for inhibition. Streptomycin resistance has decreased considerably and 91% of strains are now sensitive to 10 microgram streptomycin per ml.     

Relation between nutritional requirements and susceptibilities to antibiotics of strains of Neisseria gonorrhoeae from pharyngeal and anogenital sites.

Auxotyping and antibiotic susceptibility testing was carried out on 100 consecutive isolates of non-penicillinase producing strains of Neisseria gonorrhoeae (non-PPNG) taken on the same occasion from throat and anogenital sites, 100 non-PPNG strains isolated from the throat only, and 100 non-PPNG strains from anogenital sites only. Non-requiring, non-requiring and phenylalanine inhibited, proline requiring, amino acid group requiring, and arginine requiring auxotypes predominated in all groups of patients. Strains of the arginine requiring type found in anogenital sites tended to have additional requirements. The auxotypes and susceptibility to antibiotics of 93 of the 100 paired cultures from the throat and anogenital sites were identical. There appeared to be a slight preponderance of moderately susceptible strains in isolates from the throat. A strong correlation was found between nutritional requirements and sensitivity to antibiotics. Auxotypes of and minimum inhibitory concentrations (MICs) for N gonorrhoeae isolated from the throat were mostly the same as the auxotypes of and MICs for strains that were circulating during the study period in Amsterdam.     

Sensitivity of Neisseria gonorrhoeae to antibiotics in London (1976-78).

Three surveys of the sensitivity of pretreatment isolates of gonococci to penicillin, ampicillin, tetracycline, spectinomycin, streptomycin, and co-trimoxazole were carried out during the period 1976-78. Compared with the results of previous surveys in the London area the decline in the proportion of strains of gonococci which are insensitive to penicillin appears to have halted. No changes were found in the levels of resistance to ampicillin, tetracycline, or spectinomycin during the period surveyed, although there was a slight increase in the proportion of strains requiring concentrations of 20 microgram spectinomycin per ml for inhibition. Streptomycin resistance has decreased considerably and 91% of strains are now sensitive to 10 microgram streptomycin per ml.     

Utility of monoclonal antibody coagglutination to identify Neisseria gonorrhoeae.

The Phadebact monoclonal gonococcus coagglutination test was evaluated with 1367 (996 anogenital and 371 pharyngeal) neisserial isolates from patients who gave positive diagnostic test results for Neisseria gonorrhoeae. The overall correlation with carbohydrate utilisation was 99.7%. The Phadebact test had a specificity of 100% (286/286) and a sensitivity of 99.7% (1077/1080). The three non-reactive strains were epidemiologically linked and were of a very unusual serovar. Unlike polyclonal antibody based tests, the monoclonal antibody test provides reliable identification of gonococci from anogenital and pharyngeal sites. Because non-reactive strains are rare, however, negative anogenital isolates from heterosexual patients should be tested biochemically. The use of two reagents comprising separate pools of monoclonal antibodies against gonococcal protein IA and IB permitted the identification of an appreciable number of double infections, which would otherwise have been missed. Genital, rectal, and pharyngeal isolates from the same patient should be identified individually.     

淋球菌流行株对抗生素敏感性的研究

目的 了解淋球菌流行株对抗生素的敏感性。方法 对１９９８年～１９９９年间广东省湛江地区分离出的９８株淋球菌流行株,在系统鉴定的基础上,进行了抗生素敏感性的测定,以琼脂稀释法测定了青霉素、四环素、壮观霉素、头孢三嗪和环丙沙星的最小抑菌浓度（ＭＩＣ）,并根据ＣＤＣ标准判定敏感、中度敏感及耐药。结果 青霉素、四环素、壮观霉素、头孢三嗪及环丙沙星耐药率分别为２３．９２％、４９．４５％、１１．１１％、１６．     

Chemotaxis of polymorphonuclear leukocytes from donors of different races toward Neisseria gonorrhoeae of three different auxotypes

Urethral gonorrhea is typified by the presence of large numbers of polymorphonuclear leukocytes, which are presumably attracted to the urethra by an as yet uncharacterized chemotaxin. Culture supernatants from three different auxotypes of Neisseria gonorrhoeae, one requiring arginine, hypoxanthine, and uracil (Arg-,Hyx-,Ura-), one requiring proline, arginine (not satisfied by ornithine), and uracil (Pro-,Arg-[Orn*],Ura-), and one requiring proline (Pro-), were tested for their chemotactic activity against leukocytes from men of two racial groups, white and black. These auxotypes were chosen because the Pro- auxotype is isolated more frequently from black patients, and the Arg-,Hyx-,Ura- and the Pro-,Arg-(Orn*),Ura- auxotypes are isolated more frequently from white patients. Chemotaxis was tested in blind-well chambers in the absence of complement; membranes with a pore size of 3 microns were used. The culture supernatants of the Pro- auxotype were the most chemotactic, while those of the Arg-,Hyx-,Ura- were the least chemotactic when analyzed by a three-way analysis of variance: F = 22.83, df = 2.6, P less than .001. There were no differences in migration with respect to the race of the donor. Gonococcal culture supernatants did not require complement for chemotaxis.     

Multicenter, comparative study of enoxacin and ceftriaxone for treatment of uncomplicated gonorrhea

The efficacy of single dose enoxacin, 400 mg was compared to ceftriaxone, 250 mg IM for therapy of uncomplicated gonorrhea in 152 evaluable patients attending sexually transmitted disease clinics in Baltimore, Indianapolis and Seattle. Anogenital gonorrhea was cured in 75 (99%) of 76 patients treated with enoxacin and 73 (97%) of 75 patients treated with ceftriaxone. Three of three patients with pharyngeal gonorrhea were not cured by enoxacin while all three ceftriaxone treated cases of pharyngeal gonorrhea were cured. All cases of anogenital gonorrhea caused by beta-lactamase producing Neisseria gonorrheae (11 patients), gonococci with high-level, plasmid-mediated tetracycline resistance (11 patients), or gonococci with chromosomally mediated penicillin resistance (22 patients) were cured. The IC90 for enoxacin of N. gonorrhoeae isolated in this study was 0.06 microgram/ml. Enoxacin appears to be a well tolerated, efficacious alternative to currently recommended therapy for patients with uncomplicated, anogenital gonorrhea including cases potentially caused by antibiotic resistant N. gonorrhoeae.