non-PPNG Strains Research Articles

Serological ecology of Neisseria gonorrhoeae (PPNG and non-PPNG) strains: Canadian perspective.

One hundred and thirty eight penicillinase producing Neisseria gonorrhoeae (PPNG) and 239 non-PPNG strains were characterised serologically using a panel of seven monoclonal antibodies directed against protein 1A and seven against protein 1B. An association between serovar and susceptibility to antimicrobial agents, auxotype, and plasmid content was observed. Serogroup WI strains were more sensitive to penicillin, ampicillin, tetracycline, erythromycin, cefoxitin, and cefuroxime. Sixty five (82%) of the 79 WI strains were typed as being serovar Aedgkih, and 47 (72%) of these strains required arginine, uracil, and hypoxanthine for growth (AUH-). Seventy one (44%) of 160 WII/WIII strains were serovar Bacejk, and 42 (59%) of these required proline, citrulline, and uracil for growth (PCU-) and were plasmid free. Serovars Bcgk, Beghjk, Bacjk, and Bajk were associated with resistance to antimicrobial agents. Analysis of PPNG isolates showed a new serovar, Af, which was associated with strains imported from Malaysia and Singapore that required proline and ornithine for growth (Pro-Orn-) and carried the 24.5 megadalton transfer plasmid, the 2.6 megadalton cryptic plasmid, and the 4.5 megadalton penicillinase producing plasmid. Other associations between serovar and geographical location were noted.

Single dose cefoxitin in treating uncomplicated gonorrhoea caused by penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG strains.

A total of 136 patients with uncomplicated gonorrhoea were treated with intramuscular cefoxitin 2 g (25 patients) or 1 g (111 patients) and oral probenecid 1 g. Cefoxitin 1 g cured 95% (42 out of 45 men and all of 14 women) with infections caused by penicillinase producing Neisseria gonorrhoeae (PPNG) strains and 98% (all of 38 men and 13 out of 14 women) with non-PPNG infections, giving an overall cure rate of 96%. The rate of postgonococcal urethritis (PGU) in men treated with 1 g cefoxitin was 28%. No serious side effects of treatment were observed in patients treated with either dose. The failure rate of 7% in men infected with PPNG strains who were treated with the 1 g dose is, however, disturbing. We therefore recommend that intramuscular cefoxitin 2 g and oral probenecid 1 g may be used to treat uncomplicated gonorrhoea, especially in areas where PPNG strains are common.

Antimicrobial activity of seven metallic compounds against penicillinase producing and non-penicillinase producing strains of Neisseria gonorrhoeae.

The in vitro activity of seven metallic compounds was tested against penicillinase (beta lactamase) producing strains of Neisseria gonorrhoeae (PPNG) and non-PPNG strains. On a weight basis, the mercurials showed the greatest in vitro activity. Phenylmercuric borate, thiomersal, and mercuric chloride inhibited 90% of all strains at concentrations of 5 mg/l, 5 mg/l, and 20 mg/l respectively. Silver nitrate inhibited 90% of the strains at 80 mg/l and the MIC90 for mild silver protein was 200 mg/l. Copper and selenium salts had lower in vitro activities, inhibiting 90% of all the strains at 320 mg/l and 640 mg/l respectively. Silver nitrate and the six other compounds tested showed equal activities against PPNG and non-PPNG strains. This finding supports the recommendation for prophylaxis of gonococcal conjunctivitis of the newborn with 1% silver nitrate eye drops.

Incidence of gonorrhoea due to penicillinase producing Neisseria gonorrhoeae in Japan 1981-3 and treatment using a new antibiotic combination, BRL25000 (amoxycillin and clavulanic acid).

During the three years 1981-3, 134 (9.1%) of 1473 patients presenting at our clinics were found to be infected with penicillinase producing strains of Neisseria gonorrhoeae (PPNG). Minimum inhibitory concentrations (MICs) of benzylpenicillin and ampicillin against these PPNG strains were 8 mg/l or more, whereas against non-PPNG strains they were consistently 4 mg/l or less. In contrast, the MIC of BRL25000 (two parts amoxycillin and one part clavulanic acid, the beta lactamase inhibitor) was 4 mg/l or less even against PPNG strains. MICs of a number of other drugs commonly used to treat gonorrhoea, such as cephaloridine, cefoxitin, tetracycline, doxycycline, minocycline, kanamycin, and spectinomycin, showed no appreciable differences between non-PPNG and PPNG strains and the MIC of cephaloridine in particular was relatively high. BRL25000 proved to be very effective in the treatment of PPNG infection and cured all of 121 patients treated. A daily dose of 2.25g, cured 105 patients in two days, 11 patients in three days, four patients in four days, and one patient in five days. A new rapid diagnostic method for detecting PPNG strains, capable of application at an outpatient clinic and providing a result on the following day, is described.

Three regimens of procaine penicillin G, Augmentin, and probenecid compared for treating acute gonorrhoea in men.

The efficacy of three penicillin regimens in treating uncomplicated gonorrhoea in men was evaluated. The regimens consisted of: Augmentin 3.25 g plus probenecid 1 g orally: aqueous procaine penicillin G 4.5 MIU intramuscularly and probenecid 1 g plus one tablet of Augmentin 375 mg orally; or aqueous procaine penicillin G 4.5 MIU intramuscularly and probenecid 1 g plus two tablets of Augmentin 375 mg orally. Cure rates for infections caused by penicillinase (beta lactamase) producing Neisseria gonorrhoeae (PPNG) were 87% (20/23) for regimen 1, 97% (28/29) for regimen 2, and 95% (19/20) for regimen 3. Thus the addition of one or two tablets of Augmentin 375 mg to aqueous procaine penicillin G and probenecid cured 96% (47/49) of infections caused by PPNG strains. All three regimens were 100% effective in eradicating infections caused by non-PPNG strains. Post gonococcal urethritis occurred in 24% of cases treated with regimen 1, 14% of cases treated with regimen 2, and 15% of cases treated with regimen 3. The geometric minimum inhibitory concentrations (MIC90) of Augmentin for 72 PPNG and 162 non-PPNG isolates of N gonorrhoeae obtained before treatment were 1.98 and 0.55 mg/l, respectively. Regimen 2, besides being effective against infections caused by PPNG or non-PPNG strains, has the advantage of cost effectiveness and low toxicity. This regimen may be useful in treating gonorrhoea in areas of high prevalence of PPNG strains, such as South East Asia and Africa.

Plasmid Profiles of Neisseria gonorrhoeae in Peninsular Malaysia

The plasmid profiles of 160 strains of Neisseria gonorrhoeae isolated in Peninsular Malaysia, comprising 80 penicillinase-producing (PPNG) and 80 non-penicillinase-producing (non-PPNG) isolates, were determined. The 80 PPNG isolates were divided into two plasmid groups. All of them harbored two common plasmid species, a 4.4 megadalton (Md) R plasmid previously associated with beta-lactamase production in PPNG strains from the Far East and a 2.6 Md multicopy plasmid of unknown function. In addition to these two plasmids, 60 (75%) PPNG isolates also carried a large 24.5 Md conjugative plasmid. In contrast, the 80 non-PPNG strains were divided into three plasmid groups. All of them possessed the 2.6 Md cryptic plasmid, and 35 (44%) isolates also harbored the 24.5 Md transfer plasmid. Besides these two plasmids, one non-PPNG isolate carried an additional 7.8 Md cryptic plasmid.

Antimicrobial susceptibility testing and phenotyping of Neisseria gonorrhoeae isolated from patients with ophthalmia neonatorum in Nairobi, Kenya.

Antimicrobial susceptibility testing, auxotyping-serotyping, and plasmid analysis were performed on 41 ocular isolates, 7 nasopharyngeal isolates, and 18 cervical isolates of Neisseria gonorrhoeae obtained during a recent treatment trial of gonococcal ophthalmia neonatorum in Nairobi, Kenya. Fourteen distinct serovar-auxotype patterns were observed with IB-1/Pro-strains which accounted for 59% of the isolates. Infection with multiple types of gonococci appeared to occur in 22% of the mothers since 4 of 18 paired maternal cervical and neonatal ocular isolates had mismatched serovar-auxotype patterns. Among 10 treatment failure isolates only 1 had a mismatched serovar-auxotype pattern. Six (15%) of the ocular isolates were penicillinase-producing N. gonorrhoeae (PPNG). Five had the 4.4-megadalton (Md) beta-lactamase plasmid and one had the 3.2-Md beta-lactamase plasmid. The 24.5-Md plasmid was found in 5 of 6 PPNG strains and in 8 of 35 non-PPNG strains (P less than 0.02). For most antimicrobial agents, PPNG and non-PPNG strains showed similar patterns of susceptibility. Ceftriaxone was the most active of the antibiotics tested, with all strains having an MIC less than or equal to 0.06 mg/liter. Among non-PPNG strains, 15 (43%) had a penicillin MIC greater than or equal to 2 mg/liter and were considered intrinsically resistant to penicillin. Overall, non-PPNG intrinsically resistant strains had greater resistance to other antibiotics than did non-intrinsically resistant strains (P less than or equal to 0.006). The Mtr phenotype was found in 53% of these strains.

Phenotypic and genotypic characterization of penicillinase-producing strains of Neisseria gonorrhoeae.

Thirty penicillinase-producing Neisseria gonorrhoeae (PPNG) strains, 26 representing 9 serovars of the protein IB and 4 representing 2 serovars of the protein IA serogroup, had 10 different patterns when investigated by the restriction enzyme (RE) technique with Hind III enzyme. One RE pattern dominated, representing 11 strains with 6 different serovars of both the protein IA and IB serogroup. Identical serovars and RE patterns were found among 7 patients (3, 2 and 2, respectively) with positive epidemiology. The majority of the strains (24/30) were resistant to, or showed decreased sensitivity to, doxycycline with minimum inhibitory concentrations between 1 and 8 mg/l, consistent with the Far East origin. All the 30 PPNG strains showed by agarose gel electrophoresis to harbour a 2.8 Mdalton, a 4.4 Mdalton, as well as a 24.5 Mdalton plasmid, whereas the two non-PPNG strains had only the 2.8 Mdalton plasmid.

Single dose oral amoxycillin 3 g with either 125 mg or 250 mg clavulanic acid to treat uncomplicated anogenital gonorrhoea.

A single supervised oral dose of amoxycillin 3 g combined with clavulanic acid 125 mg as a suspension (Augmentin 3.125G) plus probenecid 1 g, cured 97 of 100 assessable patients who had uncomplicated anogenital gonorrhoea. Thirteen of the 100 patients were infected with penicillinase producing strains of Neisseria gonorrhoeae (PPNG) and 11 (85%) of these patients were cured, including one infected with a PPNG strain that was also resistant to spectinomycin. Another group of 93 assessable patients was treated with ampicillin 3 g plus probenecid 1 g, and only 85 (91%) patients were cured. Of the eight treatment failures in this group, five were found to be infected with PPNG strains. In a second study 144 assessable patients were treated with amoxycillin 3 g combined with clavulanic acid 250 mg, (Augmentin 3.250G) plus probenecid 1 g, and a 97% cure rate was again obtained. Five of seven (71%) patients infected with PPNG strains were cured. Although both Augmentin regimens were effective for treating gonorrhoea caused by PPNG and non-PPNG strains, side effects were noted in more patients treated with 250 mg clavulanic acid (24%) than with 125 mg clavulanic acid (5%). In addition, a similar cure rate was obtained in the three primary sites of infection, the urethra, cervix, and rectum.

Auxotypes and serogroups of penicillinase producing and non-producing strains of Neisseria gonorrhoeae isolated in Franceville, Gabon.

The auxotypes and serogroups of 250 consecutive isolates of Neisseria gonorrhoeae from Franceville, Gabon, including 33 penicillinase producing (PPNG) strains, were identified and the results tabulated for four periods. The PPNG and certain non-PPNG strains were isolated in clusters against a relatively stable pattern of non-PPNG biotypes. Most of the non-PPNG strains were non-requiring or proline requiring strains of serogroup WII or non-requiring strains that could not be grouped with commercially available antisera. No strain requiring arginine, hypoxanthine, and uracil was observed. The PPNG strains were all serogroup WI or ungroupable and non-requiring or proline or arginine dependent auxotypes. Only one non-PPNG strain required proline or arginine and was not serogroup WII.

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.

Activity of nine antibacterial agents on penicillinase- and nonpenicillinase-producing Neisseria gonorrhoeae isolated from clinical specimens obtained in northern Norway.

34 penicillinase-producing (PPNG) and 102 nonpenicillinase producing (non-PPNG) strains of Neisseria gonorrhoeae were tested against 9 antibacterial agents. Cefoxitin, latamoxef, cefotaxime and imipenem inhibited all PPNG (MIC less than 2 mg/l); chloramphenicol (2 mg/l) inhibited 86%, and 3% and 8%, respectively, were inhibited by 1 mg/l of doxycycline when disk diffusion or agar dilution sensitivity testing were performed. All PPNG strains were sensitive to spectinomycin (MIC less than 32 mg/l). Non-PPNG strains were uniformly sensitive to all antibacterial agents, doxycycline being slightly less active than the other compounds.

Susceptibility to antimicrobials of Neisseria gonorrhoeae isolated in Singapore: implications on the need for more effective treatment regimens and control strategies.

The antimicrobial susceptibility of gonococci isolated in Singapore has been studied over several years. In 1983, the prevalence of penicillinase producing Neisseria gonorrhoeae (PPNG) was 33.5% and 64% of non-PPNG isolates had minimum inhibitory concentrations (MICs) of penicillin of greater than or equal to 0.5 mg/l. After a control programme, the isolation of the gonococcus from prostitutes was reduced and there was improvement in its susceptibility to antimicrobials. The incidence of PPNG strains was stabilised with a change in the treatment regimen. An influx of foreign prostitutes, however, had an unfavourable impact on these variables. Countries in South East Asia have a high prevalence of PPNG and non-PPNG strains that have reduced susceptibility to antimicrobials. In view of increased air travel the problem should be seen from a global perspective. Better treatment regimens and control strategies are urgently needed.

Antimicrobial susceptibility of Neisseria gonorrhoeae isolated in Durban, South Africa.

One hundred and forty clinical isolates of Neisseria gonorrhoeae were screened for production of penicillinase by the intralactam strip method and chromogenic cephalosporin test. Minimum inhibitory concentrations (MICs) of penicillin, ampicillin, tetracycline, cefoxitin, cefuroxime, cefotaxime, sulphamethoxazole-trimethoprim (ratio 19/1), and spectinomycin, were measured for 100 strains by the agar dilution method. Seven (5%) of the 140 isolates were identified as penicillinase producing N gonorrhoeae (PPNG). The MICs of penicillin for the seven PPNG strains ranged from 0 X 25 mg/1 to 2 mg/1. Of the 93 non-PPNG strains, 80 (86%) were fully susceptible to penicillin with MICs ranging from 0 X 0037 mg/1 to 0 X 06 mg/1 and 13 (14%) were of intermediate penicillin resistance with MICs greater than or equal to 0 X 125 mg/1. Of the 100 isolates tested, 86% were fully susceptible to tetracycline with MICs of less than 1 mg/1. No spectinomycin resistant strains were encountered in this study. All gonococcal strains were susceptible to the cephalosporins tested as well as to sulphamethoxazole-trimethoprim.

Treatment of uncomplicated gonorrhoea with rosoxacin (acrosoxacin).

An open study was designed primarily to evaluate the efficacy of rosoxacin in the treatment of gonorrhoea caused by penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG strains. A total of 199 patients (99 men and 100 women) satisfactorily completed follow up examinations, 50 men and 50 women having received rosoxacin 300 mg orally and the remainder having received kanamycin 2 g intramuscularly. Rosoxacin achieved an overall cure rate of 94% (96.7% for PPNG and 90% for non-PPNG strains). In patients treated with kanamycin the overall cure rate was 89.9% (92.7% for PPNG and 83.3% for non-PPNG strains). A correlation between treatment failures and minimum inhibitory concentrations (MICs) of rosoxacin was noted in non-PPNG strains but not in PPNG strains. Side effects which were mild and self limiting were noted in 15 of 100 patients treated with rosoxacin. The high failure rates associated with non-PPNG strains requiring MICs of 0.125 mg/l and the observation of a substantial rise in the MICs for isolates after treatment is of concern. Otherwise, rosoxacin in a single dose of 300 mg appears to be safe and effective for the treatment of uncomplicated gonorrhoea.

Epidemiological characterisation of Neisseria gonorrhoeae isolates from the Far East.

One hundred strains of Neisseria gonorrhoeae (including 30 penicillinase producing (PPNG) strains) originating from Korea were characterised by plasmid analysis, auxotyping, and serogrouping. Eighty per cent of the isolates possessed the conjugative 24.5 megadalton (Mdal) plasmid. A novel 7.8 Mdal plasmid was present in four isolates (one PPNG and three non-PPNG strains). Seventy five per cent of all the strains tested were wild type and belonged to serogroup WII, while 20% were proline requiring and belonged to serogroup WII. Two of the remaining strains were tyrosine auxotrophs, while another strain was arginine requiring; these three strains carried the conjugative plasmid and belonged to serogroup WII.

Penicillinase-producing Neisseria gonorrhoeae isolates from different localities in south east Asia. Susceptibility to 15 antibiotics.

Sixty four penicillinase-producing Neisseria gonorrhoeae (PPNG) and 24 non-penicillinase-producing (non-PPNG) strains isolated from six different south east Asian localities were tested by the agar dilution method against 15 antibiotics. All isolates were susceptible to spectinomycin and sulphamethoxazole-trimethoprim (19:1 ratio). A large proportion of both PPNG and non-PPNG strains showed, however, a decreased susceptibility to tetracycline, kanamycin, and erythromycin: 49% with minimum inhibitory concentrations (MICs) of tetracycline greater than or equal to 2 micrograms/ml, 34% with MICs of kanamycin greater than or equal to 32 micrograms/ml, and 80% with MICs of erythromycin greater than or equal to 2 micrograms/ml. These MIC cut-off values were chosen since they are close to the highest concentrations of these antibiotics attainable in serum after drug administration. Resistance to these antibiotics was not related to penicillinase production and does not appear to be confined to gonococci isolated from one particular locality. Strains showing resistance concurrently to two or three of these drugs were often isolated from different south east Asian countries. All eight cephalosporins tested were effective against both PPNG and non-PPNG strains. On a weight to weight basis the new cephalosporins--namely, moxalactam, cefoperazone, cefotaxime, and ceftriaxone--were the most effective. In contrast to those of cefoxitin, cefuroxime, moxalactam, and cefoperazone the MICs of cefamandole, cefotaxime, and ceftriaxone were significantly affected when the inoculum size was increased from 10(3) to 10(6) colony forming units (cfu).

Antibiotic sensitivity patterns of penicillinase-positive and penicillinase-negative strains of Neisseria gonorrhoeae isolated in Fukuoka, Japan.

Penicillinase production and minimum inhibitory concentrations (MICs) of penicillin G, amoxycillin, doxycycline, and spectinomycin were studied for 155 gonococcal strains isolated in Fukuoka, Japan, between April and December 1981. Of 155 isolates, 25 (16.1%) strains were identified as penicillinase-producing Neisseria gonorrhoeae (PPNG) by a rapid iodometric test. The antibiotic sensitivity of 130 penicillinase-negative (non-PPNG) and 25 PPNG strains was compared. The mean MIC of penicillin G for non-PPNG strains was 0.65 microgram/ml. Twenty-five PPNG strains had MICs of penicillin G between 6.25 and greater than 100 micrograms/ml. The susceptibility to amoxycillin and doxycycline of PPNG strains was significantly lower than that of non-PPNG strains. All the strains proved to be sensitive to spectinomycin. The MICs of four antibiotics for non-PPNG strains were significantly correlated.

Culture medium for confirmation of penicillin-resistant and penicillinase-producing Neisseria gonorrhoeae.

A culture method for the isolation and identification of penicillinase (beta-lactamase)-producing Neisseria gonorrhoeae (PPNG) was evaluated in the Philippines where PPNG are common. The method uses plastic biplates containing standard Martin-Lewis gonorrhea culture medium in one side of the biplate and PPNG-selective medium containing 1.5 microgram of penicillin G per ml and a suspension of Sarcina lutea (Micrococcus lutea) that was susceptible to 0.01 microgram of penicillin G per ml in the other side. Penicillin-resistant gonococci grow on both sides of the biplate. The hydrolysis of penicillin by beta-lactamase permits the growth of S. lutea around PPNG colonies. With this medium we successfully identified 11 of 12 PPNG strains growing on primary isolation plates. A 48- to 72-h incubation period was needed, however, for visible growth of S. lutea around PPNG colonies. A unique advantage of this method was the identification of non-PPNG strains which also grew on penicillin-containing medium but did not allow growth of S. lutea. These relatively penicillin-resistant strains were the cause of infections which were not cured by penicillin treatment in 2 of 11 patients.

ANTIBIOTIC SUSCEPTIBILITY OF NEISSERIA GONORRHOEAE IN RELATION TO SEROGROUPS

Susceptibility testings, by means of the agar-dilution method, were performed on nine antibiotics of 138 non-PPNG (beta-lactamase-producing = PPNG) strains, 17 of which originated from Thailand, and 88 PPNG isolates. The gonococcal strains were sero-grouped by the co-agglutination method and classified among the sero-groups W I, W II or W III. Statistically significant differences in antibiotic susceptibility between non-PPNG strains of the three sero-groups could be demonstrated with strains belonging to sero-group W I as the most sensitive and W III isolates as the most resistant. Non-PPNG strains from Thailand were significantly more resistant than the other non-PPNG isolates of the same sero-group. There was, however, no significant difference in resistance between non-PPNG strains from Thailand and PPNG isolates of the same sero-group. PPNG strains of sero-group W I were significantly more sensitive than PPNG strains of sero-group W II, whereas there was no significant difference between PPNG isolates of sero-groups W II and W III. Non-PPNG strains, not from Thailand, of sero-groups W I and W II were significantly more susceptible to non beta-lactam antibiotics than PPNG strains of corresponding sero-groups, while no such difference could be demonstrated for non-PPNG and PPNG isolates of sero-group W III.