Penicillinase-producing Neisseria Gonorrhoeae Strains Research Articles

Identification of TEM-135 beta-lactamase in penicillinase-producing Neisseria gonorrhoeae strains in Japan.

Ten penicillinase-producing Neisseria gonorrhoeae (PPNG) strains isolated from 2000 to 2008 were characterized by multilocus sequence typing, multiantigen sequence typing, and plasmid typing. Sequence analysis showed that 8 strains contained a TEM-1 beta-lactamase gene. However, two other genetically distinct PPNG strains, isolated in 2004 and 2008, each contained a TEM-135 beta-lactamase on different plasmids, a Toronto/Rio type R plasmid and an Asia type R plasmid, suggesting independent origins of these PPNG strains.

Penicillinase producing Neisseria gonnorhoeae: the review of the present situation in Ibadan, Nigeria

All the isolates of Neisseria gonorrhoeae from patients that attended special treatment Clinic, University College Hospital, Ibadan, Nigeria between 15th January 1997 and 15th December 1999 were studied so as to review the present prevalence rate of penicillinase producing Neisseria gonorrhoeae (PPNG) in Ibadan. Of the 214 patients that had gonococcal infections, 161 were male (75.2%) and 53 (24.8%) were female. Ninety-two (57.1%) of the male and 28(52.8%) of the female were aged between 20- 29 years while 19.9% of the male and 15.1 % of the female were in the age of 40 and above. The sex difference is not statistically significant (chi2=2.19, df=3, p=0.53). The present study revealed that PPNG strains have increased dramatically to 98.6 per cent. This has posed a great threat to the usefulness of penicillin and ampicillin as the drugs of choice in gonococcal therapy in Nigeria.

Surveillance of antibiotic resistance in Neisseria gonorrhoeae in The Netherlands, 1977-95.

OBJECTIVE: To evaluate the prevalence and epidemiology of penicillinase producing Neisseria gonorrhoeae (PPNG) and tetracycline resistant N gonorrhoeae (TRNG) in the period 1977-95 in the Netherlands. To compare auxotypes, serovars,...

Diversity of isolates of penicillinase-producing Neisseria gonorrhoeae (PPNG) in Honolulu, Hawaii: 1982-1991.

Gonococcal infections caused by penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates have increased in geographic distribution and prevalence. It was postulated that PPNG strains would become endemic in Honolulu and that, in turn, this city would serve as a reservoir for the introduction of PPNG strains into the continental United States. To assess the role of Honolulu as a reservoir for PPNG strains by assessing the diversity and persistence of PPNG strains between 1982 and 1991. A total of 432 PPNG strains were characterized by auxotype/serovar (A/S) class and plasmid content, and their distribution during the 10-year period was studied. Of 432 isolates, 373 (86.4%) possessed a 4.4-Mdal beta-lactamase plasmid; 39 (9.0%) possessed a 3.2-Mdal beta-lactamase plasmid; and 20 (4.6%) possessed a 3.05-Mdal beta-lactamase plasmid. A total of 53 A/S classes were identified. Asian, African, and Toronto PPNG strains belonged to 49 (92.5%), 15 (28.3%), and 11 (20.7%) A/S classes, respectively. Though all Toronto PPNG strains possessed a 24.5-Mdal conjugative plasmid, these plasmids could not be transferred by conjugation. Although some apparent microepidemics of PPNG strains were identified, most strains were isolated sporadically. A large number of different strains have been associated with PPNG infections in Honolulu, but there was no evidence that any strain persisted endemically during the study period. These observations have important implications for the design and assessment of community gonorrhea control strategies.

Survey on Antibiotic Sensitivity of Neisseria gonorrhoeae Strains Isolated in China, 1987–1992

The appearance and the endemic of penicillinase-producing Neisseria gonorrhoeae (PPNG) and other resistant strains cause much difficulty in the treatment of gonorrhea. To keep surveillance of the strains is important for the control of gonorrhea nationwide. To know the resistance to antibiotics of Neisseria gonorrhoeae strains isolated in China. The minimum inhibitory concentration (MIC) to penicillin, spectinomycin, and cephalosporins was determined by the agar plate dilution test in strains of N. gonorrhoeae submitted from six cities in various areas of the country during the period 1987-1992, and the prevalence of penicillinase-producing N. gonorrhoeae strains were examined by the rapid idometric method. The resistant strains to penicillin (MIC > or = 1.0 microgram/ml) accounted for 57.5% of all isolates. The resistant strains to spectinomycin (MIC > or = 128 micrograms/ml) made up 1.3% and the strains which had a MIC closing resistance (MIC = 64 micrograms/ml) accounted for 4%. There were 18 PPNG strains (4.3%) in 419 isolates from Nanjing and Nanning city. The resistant strains to ceftrixone and cefotaxime accounted for 2.6% and 4.2%, respectively. The situation of N. gonorrhoeae resistance to penicillin is rather serious in the country and relevant measures should be taken in the choice of therapeutic drugs, the follow-up of patients and the surveillance of gonorrhea.

The emergence of penicillinase-producing Neisseria gonorrhoeae strains carrying the 4.9 kb (Toronto) plasmid in Denmark and of a novel large plasmid in two nonpenicillinase-producing Neisseria gonorrhoeae strains.

This study comprised plasmid analysis and antimicrobial susceptibility testing of 712 out of a total of 730 penicillinase-producing Neisseria gonorrhoeae (PPNG) and 744 random non-PPNG strains isolated in Denmark between 1985 and 1990. The rate of patients with PPNG infections rose from 1% to 2% during 1985-1987 to 6.9% in 1989, and then decreased to 4.8% in 1990. A decrease in cases of gonorrhea from 9,798 to 1,990 was seen during the same period. Strains harboring the 4.9 kb (Toronto) plasmid first appeared in 1987; in 1988-1990, 65% to 78% of strains from patients with PPNG infections acquired in Denmark contained this plasmid. The majority of these strains seemed to belong to a single clone. Tetracycline-resistant PPNG strains (MIC greater than 32 mg/L) first appeared in Denmark in 1989, and tetracycline-resistant non-PPNG strains carrying a 40 kb plasmid (tetM?) first appeared in 1990. A novel 41-42 kb plasmid appeared in one strain in 1987 and another in 1988. The minimum inhibitory concentration (MIC) of tetracycline for these two strains was 4 mg/l. The significance of this plasmid is yet unknown.

Neisseria gonorrhoeae in Athens, Greece

The incidence of gonorrhoea cases diagnosed in a major venereal hospital of Athens, Greece, was markedly reduced between 1986 and 1989. All 182 gonococcal isolates found during this period were epidemiologically classified into Sero-/Auxo-/Plasmid content (S/A/Pc) types. Susceptibility to six antimicrobials was also determined. Penicillinase-producing Neisseria gonorrhoeae (PPNG) strains were isolated in an increased frequency of 7.7% and a striking shift in their distribution into S/A/Pc types was noted from previous years. The isolates exhibited wide heterogeneity of type: none of the 14 PPNG strains was identical, while the 168 non-PPNG strains were distributed into 64 S/A/Pc types. Fifty-seven percent (57%) of the PPNG and 86% of the non-PPNG isolates were of the WII/III serogroup. Chromosomally mediated resistance to penicillin, ampicillin, or both was exhibited by 14% of the non-PPNG isolates. Greater frequency of reduced susceptibility to cefotaxime, tetracycline, and chloramphenicol was also found among PPNG and non-PPNG strains, mostly of the WII/III serogroup. Twelve percent (12%) of the non-PPNG and 57% of the PPNG strains had multiple patterns of resistance, involving 2 to 4 antimicrobials of different class lines.

Increase of the Relative Frequency of Penicillinase-producing Neisseria gonorrhoeae Strains to more than Five per Cent in Munich

The relative frequency of penicillinase-producing Neisseria gonorrboeae strains isolatedfrom Munich STD patients nowadays clearly exceeds five percent. Penicillin resistance is either due to the 3.2 or 4.4 Megadalton plasmid. Similar trends are reported from other European countries. Therefore, treatment with third generation cephalosporins such as ceftriaxone, cefotaxime or others is now generally advisable not only in the Far East and Central Africa but also in Central Europe.

Serological classification in relation to auxotypes, plasmid contents, and susceptibilities to antimicrobials of PPNG and non-PPNG strains isolated in Greece.

Thirty three penicillinase producing Neisseria gonorrhoeae (PPNG) and 152 non-PPNG strains were serologically classified in relation to their patterns of resistance to antimicrobials, nutritional requirements (auxotypes), and plasmid contents. Of the 185 strains, 65 (35%) belonged to the WI and 120 (65%) to the WII/III serogroup, the predominant serovars of which were Arost and Bropt, respectively. Associations between serotype and susceptibility to antimicrobial agents, auxotype, and plasmid content were observed. Of the 152 non-PPNG strains, 112 (74%) belonged to serogroup WI. The WI non-PPNG strains were more sensitive to penicillin, thiamphenicol, tetracycline, and cefotaxime than the WII/III non-PPNG strains. Auxotyping and serogrouping the strains showed no differentiation other than that arginine, hypoxanthine, and uracil dependent (AHU-) strains belonged to serogroup WI. The proline, citrulline, and uracil dependent (PCU-) strains belonged, as expected, to serogroup WII/III. Analysing the 33 PPNG strains showed that of 21 carrying the 4.5 megadalton (Asian type) penicillin resistance plasmid, 17 (81%) belonged to serogroup WI, with serovar Arst predominating, and only four (19%) to serogroup WII/III. Of 11 isolates carrying the 3.2 megadalton (African type) resistance plasmid, seven (64%) belonged to serogroup WI (serovar Av predominating) and four (36%) to WII/III (with serovar Bropyst predominating). One strain carried the 3.05 megadalton penicillin resistance plasmid (Toronto type), belonged to the WI serogroup, and had serovar Arost.

Plasmid content, auxotype and protein-I serovar of gonococci isolated in the Gambia

Twenty-nine strains of penicillinase-producing Neisseria gonorrhoeae (PPNG) and 30 non-penicillinase-producing strains, all isolated in the Gambia, were characterized in terms of their plasmid content, auxotype and protein-I serovar. Sixty-two per cent of the PPNG strains contained the 3.2 MDa penicillinase-coding plasmid, and 38% had the 4.4 MDa plasmid. All the PPNG strains contained the 2.6 MDa cryptic plasmid but lacked the 24.4 MDa conjugative plasmid. In contrast, 46.7% of the non-PPNG strains harboured only the cryptic plasmid while 16.7% contained both the cryptic and conjugative plasmids. Seventeen per cent of the non-PPNG strains contained the conjugative plasmid only and 20% lacked plasmids. The PPNG and non-PPNG strains also differed in terms of their protein-I serovar. Eighty-six per cent of the PPNG strains belonged to serogroup 1 A, whereas the majority (60%) of non-PPNG strains belonged to serogroup 1 B. There was no significant difference in the auxotypes of the PPNG and non-PPNG strains, with both groups consisting predominantly of prototrophic and proline-requiring strains, with a minority of strains requiring arginine. When the 59 strains were each characterized in terms of their combined plasmid profile, auxotype and serovar, 39 different combinations were noted, which indicates the heterogeneous nature of the gonococcal population found in the Gambia.

Chromosomally mediated intrinsic resistance to penicillin of penicillinase producing strains of Neisseria gonorrhoeae isolated in Sydney: guide to treatment with Augmentin.

Single dose Augmentin treatment fails to cure an appreciable proportion of patients infected with penicillinase producing Neisseria gonorrhoeae (PPNG) strains in parts of the world where high levels of chromosomally mediated intrinsic resistance are also present in gonococci. The levels of intrinsic resistance to penicillin of 31 PPNG strains isolated in Sydney were assessed by obtaining beta lactamase negative variants of these strains and measuring the minimum inhibitory concentration of penicillin by agar plate dilution techniques. The levels of intrinsic resistance found in these imported PPNG strains were higher than those recorded for local isolates of non-PPNG strains, which indicates that caution should be exercised in the use of single dose Augmentin treatment of infections with PPNG strains in Sydney.

Plasmid profile of Neisseria gonorrhoeae in Nigeria and efficacy of spectinomycin in treating gonorrhoea.

The prevalence of penicillinase producing Neisseria gonorrhoeae (PPNG) strains has been steadily rising in Nigeria since 1979, and now about 80% of the strains of gonococci isolated in Ibadan are found to produce penicillinase. Spectinomycin has consequently become widely used in treating these infections. To ascertain the emergence of spectinomycin resistance, this study was undertaken to assess the in vivo susceptibilities of gonococcal strains to spectinomycin and other common antibiotics. Five hundred and twenty seven isolates were tested, of which 452 (85.5%) were PPNG strains. None of the strains were found to be resistant to 100 micrograms spectinomycin discs in vitro, whereas all 370 patients treated with the antibiotic were bacteriologically cured. Plasmid analysis shows that both "Asian" and "African" PPNG types are circulating in Nigeria. For the moment spectinomycin remains highly effective in treating gonococcal infections in west Africa.

Penicillinase producing gonococci: a spent force?

Though the incidence of gonorrhoea caused by penicillinase producing Neisseria gonorrhoeae (PPNG) strains at St Mary's Hospital rose rapidly from 1980 to reach 6.2% in 1982, it declined in 1983 (8.6%) and in 1984 (6.5%), a trend that has continued in 1985. The use of penicillinase stable antibiotics or more effective contact tracing are unlikely to be responsible for this recent decline. We have always isolated very few PPNG strains from homosexual men, and the possible effects of the acquired immune deficiency syndrome (AIDS) on sexual behaviour in this group is therefore unlikely to be relevant. We have seen a steady increase in the proportion of PPNG strains carrying the 4.4 megadalton penicillinase plasmid (67% of PPNG strains in 1984). Strains carrying both the 4.4 megadalton plasmid and the 24.5 megadalton conjugal plasmid were very common in 1982, but since then have declined in importance. PPNG strains carrying the 3.2 megadalton plasmid have become less common, and the presence of the 24.5 megadalton plasmid in these strains has not apparently led to their wider dissemination in the community. Whereas the basic pattern of PPNG auxotypes has changed little, since 1982 we have isolated an increasing number of mixed auxotypes with nutritional requirements other than just proline. PPNG strains carrying the 4.4 megadalton plasmid seem to be more resistant to erythromycin, tetracycline, and streptomycin than those carrying the 3.2 megadalton plasmid. Spectinomycin resistance has only occurred in strains carrying the 4.4 megadalton plasmid.

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.

Molecular and epidemiological analysis of penicillinase producing strains of Neisseria gonorrhoeae isolated in Canada 1976-84: evolution of new auxotypes and beta lactamase encoding plasmids.

Though the number of penicillinase producing Neisseria gonorrhoeae (PPNG) strains isolated in Canada comprises under 1% of all gonococcal isolates, it continues to increase appreciably each year. Most strains are imported from areas of endemic infection with PPNG strains. Two local outbreaks in 1984, however, were notable for the number of patients infected and for the distinctive phenotypes of the strains. One outbreak was caused by a wild type strain, of serovar BACJK with a new 3.05 megadalton penicillinase encoding plasmid, whereas the other was caused by strains with the Asia+ plasmid type, serovar AE and with a proline and ornithine requiring auxotype. Five plasmid patterns (Africa+, Africa-, Asia+, Asia-, and Toronto+) were observed among the PPNG strains. The association between plasmid content and specific auxotype (such as Asia plasmid with proline requiring auxotype or Africa plasmid with wild type auxotype) and inhibition by phenylalanine continues to be unexplained.

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.

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.

Cefoperazone (Cefobid) for treating men with gonorrhoea caused by penicillinase producing Neisseria gonorrhoeae.

The recent emergence of spectinomycin resistant penicillinase producing Neisseria gonorrhoeae (PPNG) and the high prevalence of PPNG strains among the gonococcal isolates in Seoul represent a grave challenge to the programme for controlling sexually transmitted disease (STD). Fifty men with uncomplicated gonococcal urethritis caused by PPNG strains were treated with a single intramuscular injection of 1 g cefoperazone. Forty two patients were followed up. All patients recovered including three who became reinfected and required further treatment. Two patients (4.8%) developed postgonococcal urethritis (PGU). The MIC90 of cefoperazone measured by an agar dilution susceptibility test was 0.12 mg/l.

Epidemiology of PPNG infections in the Netherlands: analysis by auxanographic typing and plasmid identification.

We carried out auxanographic typing and plasmid identification on 1380 isolates of penicillinase producing Neisseria gonorrhoeae (PPNG) isolated in the Netherlands in 1982 and found four plasmid patterns and 24 auxotypes with noticeable local or regional variations. Among 756 strains harbouring the 3 X 2 megadalton (Mdal) resistance plasmid ("African" type), with or without the 24 Mdal transfer plasmid, 667 (88%) were non-requiring and inhibited by phenylalanine. This type was endemic in most of the cities or regions we studied. Twenty methionine requiring PPNG strains were found, all harbouring the 3.2 and 24 Mdal plasmid; virtually all of them were isolated or contracted in the region of Groningen. The predominant (443 (71%) auxotype among the 624 PPNG strains containing the 4.5 Mdal plasmid ("Asian" type) (with or without the 24 Mdal plasmid) was proline requiring. This auxotype (with the 4.5 Mdal and 24 Mdal plasmid) caused an outbreak in Amsterdam, and in Groningen replaced the local methionine requiring auxotype which had the 3.2 Mdal and 24 Mdal plasmids. Many auxotypes with the 4.5 Mdal plasmid, and requiring proline only, or proline and isoleucine, circulated in the Hague. Spread of imported strains by prostitution played an important part in the epidemiology of infection with PPNG strains.

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.