Penicillinase Producing Strains Of Neisseria Gonorrhoeae Research Articles

Characterization of penicillinase-producing strains ofNeisseria gonorrhoeae

Twenty-three penicillinase-producing strains of Neisseria gonorrhoeae were characterized. All strains showed hybridization with a TEM-1 probe and production of a TEM-1 type beta-lactamase (pI 5.4) on isoelectric focusing. Eight strains also showed a beta-lactamase band of pI 5.5. The penicillin MICs for the strains producing only TEM-1 were in the range 4-16 micrograms/ml; MICs of the strains with the additional pI 5.5 band were > or = 128 micrograms/ml for seven strains and 4 micrograms/ml for an arginine-hypoxanthine dependent strain. The association of the high MICs with the presence of the pI 5.5 band was statistically significant. The pI 5.5 band could represent a new beta-lactamase type or a TEM-1 mutant.

Comparison of Single-Dose Ceftizoxime or Ceftriaxone in the Treatment of Uncomplicated Urethral Gonorrhea

Penicillinase-producing strains of Neisseria gonorrhoeae account for an increasing percentage of cases of gonorrhea in the United States. Although many strains of N. gonorrhoeae are still sensitive to penicillin, the CDC currently recommends one dose of ceftriaxone 250 mg IM for treatment of uncomplicated urethral gonorrhea. Ceftizoxime like ceftriaxone is a third generation cephalosporin that demonstrates excellent MICs against beta-lactamase positive and negative strains of N. gonorrhoeae. The clinical efficacy of a single-dose of ceftizoxime 250 mg IM was compared with ceftriaxone 250 mg IM in patients with uncomplicated urethral gonorrhea. In addition, the cost of each regimen was evaluated to determine the most cost-effective agent. A total of 106 and 98 patients were treated with ceftizoxime and ceftriaxone, respectively, with all cases cured. PPNG strains were observed in 25.5% of patients. No adverse events were observed or reported. The cost of ceftizoxime was approximately one-third that of ceftriaxone ($2.37 to $2.56 and $7.15 to $8.70 per dose, respectively). The data from this study suggest that ceftizoxime 250 mg IM is a safe, cost-effective alternative to the use of ceftriaxone 250 mg IM in the treatment of patients with PPNG-positive and -negative gonorrhea.

Comparison of ofloxacin and ceftriaxone in the treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing strains

Eighty-nine patients with uncomplicated gonorrhea, including 31 patients (34.8%) infected with penicillinase-producing strains of Neisseria gonorrhoeae, were treated with oral ofloxacin (single 400-mg dose) or intramuscular ceftriaxone (250-mg dose). All 47 patients who received ofloxacin and 41 of 42 patients who received ceftriaxone were cured.

Penicillinase-producing Neisseria gonorrhoeae in Dade County, Florida: phenotypic characterization of isolates from 1983, 1984, and 1986.

Penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) have been endemic in Miami, Florida, since 1981. Strains of PPNG isolated in Miami during 1983 (60 isolates), 1984 (41 isolates), and 1986 (107 isolates) were characterized by plasmid content, auxotype/serovar (A/S) class, and susceptibility to antimicrobial agents. In 1986, 95 isolates (89%) possessed the 3.2-Megadalton (MDa) beta-lactamase plasmid; 36 (34%) of these isolates also possessed the 24.5-MDa conjugative plasmid. These results contrast with those from 1984, when 37 PPNG isolates (90%) possessed the 4.4-MDa plasmid, and most possessed the 24.5-MDa conjugative plasmid. This in turn was a reversal of the pattern seen in 1983, when only 42 (69%) possessed the 3.2-MDa plasmid, and the conjugative plasmid was rare. In 1983 and 1986, isolates possessing the 4.4-MDa plasmid were more resistant to penicillin than were isolates containing the 3.2-MDa plasmid. All isolates were susceptible to spectinomycin and ceftriaxone. In early 1986, two A/S classes accounted for 66% of all isolates. Pro/IA-1,2 and Pro/IB-2 accounted for 31 (29%) and 40 (37%), respectively, and were isolated during every week in early 1986. In contrast, isolates belonging to 14 and six A/S classes possessing the 3.2- and 4.4-MDa beta-lactamase plasmid, respectively, were isolated sporadically. The composition of the PPNG strain population in Miami is dynamic, a factor that may have important implications for the use of traditional disease intervention strategies.

Penicillin sensitivity of gonococci isolated in Australia, 1981-6. Australian Gonococcal Surveillance Programme.

The sensitivity to penicillin of about 25,000 gonococcal isolates tested in Australia during the five years to 30 June 1986 was assessed in a collaborative multicentric study. Increasing resistance to the penicillin group of antibiotics was observed during the course of this study and was manifested both as increased levels of chromosomally mediated intrinsic resistance and by an increasing incidence of penicillinase producing strains of Neisseria gonorrhoeae (PPNG). Pronounced regional differences in the levels of intrinsic resistance, the incidence of infections with PPNG, and the endemic spread of PPNG strains were observed.

Serovars, auxotypes, and plasmid profiles of PPNG strains with Asian type plasmid isolated in Amsterdam.

In 1982 an increase of penicillinase producing strains of Neisseria gonorrhoeae (PPNG), carrying the 4.5 megadalton Asian type plasmid and the 24 megadalton transfer plasmid (Asia+), was observed in Amsterdam. The main auxotypes were proline requiring (Pro-) and proline and hypoxanthine requiring (Pro-Hyx-). Using two monoclonal antibody systems, it was shown that the serovars of strains with these auxotypes isolated in 1981 were different from those isolated in 1982, which indicated the start and end of microepidemics. Different serovars were also observed in Pro- and non-requiring (NR) Asia- PPNG strains isolated in 1981-2 and 1985 respectively. Only one serovar (Aedih/Arst) was common in strains isolated in 1981-2 as well as in 1985.

Characterisation of penicillinase producing gonococci isolated in Munich, 1981-6.

Twenty three penicillinase producing strains of Neisseria gonorrhoeae (PPNG) isolated in Munich from 1981 to 1986 were characterised in terms of their plasmid content, auxotypes, protein I serovars, and sensitivity to antibiotics. Sixteen strains (70%) harboured a 4.4 megadalton plasmid, with 13 of these strains also containing a 24.4 megadalton plasmid. Seven strains (30%) contained a 3.2 megadalton plasmid, with only one of them containing a 24.4 megadalton plasmid. Thirteen strains (57%) were prototrophic, eight (35%) required proline, one required arginine, and one required proline and arginine for growth. Serovar analysis showed that 16 strains (70%) belonged to the protein IB serogroup and comprised four serovars (IB-1, IB-5, IB-7, and IB-8). The seven strains belonging to the IA serogroup also comprised four serovars (IA-2, IA-4, IA-6, and IA-10). Although 18 different categories of plasmid, auxotype, and serovar were found in the 23 PPNG strains, there was a similarity between the auxotypes in terms of the range of serovars they comprised. Measurement of minimum inhibitory concentrations (MICs) of antibiotics for the strains showed that they were all susceptible in vitro to spectinomycin (MIC less than or equal to 32 mg/l), enoxacin (MIC less than or equal to 0.25 mg/l), cefotaxime, ciprofloxacin, and ceftriaxone (MICs less than or equal to 0.064 mg/l), whereas about half showed some resistance to tetracycline or cefotiam, or both.

Single dose piperacillin in treating uncomplicated gonococcal urethritis in men.

A single intramuscular dose of piperacillin 2 g, with probenecid 1 g orally, was used to treat 82 men with uncomplicated gonococcal urethritis due to penicillinase producing strains of Neisseria gonorrhoeae (PPNG) or non-PPNG. All 49 patients infected with non-PPNG strains were cured, as opposed to only 25 (76%) of 33 patients infected with PPNG strains, giving an overall success rate of 90%. No serious side effects of treatment were observed. Post gonococcal urethritis (PGU) occurred in 18% of the patients treated. Antibiotic susceptibility tests showed that 44 (96%) of the 46 non-PPNG strains tested had MICs of piperacillin of 2 mg/l or less and 26 (76%) of the 34 PPNG strains had MICs of 32 mg/l or more. This regimen is not recommended for use as first line treatment in areas where there is a high incidence of infection with PPNG strains. It is, however, highly effective against non-PPNG strains.

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.

Underestimation of arterial oxygen tension by transcutaneous electrode with increasing age in infants.

To investigate the effect of increasing gestational and postnatal age on the relation between transcutaneous oxygen tension (tcPO2) and arterial oxygen tension (PaO2) 160 simultaneous measurements of tcPO2 and PaO2 tensions were made on 42 infants born at 24-41 weeks' gestation and aged 0-32 weeks from birth. Irrespective of gestational age a progressive fall in the tcPO2:PaO2 ratio with increasing postnatal age was found. At all postnatal ages tcPO2:PaO2 tended to be lower in the more mature infants.

Penicillinase producing strains of Neisseria gonorrhoeae in the West Midlands 1979-83.

All cases of gonorrhoea caused by penicillinase producing strains of Neisseria gonorrhoeae (PPNG) occurring in the population served by the West Midlands Regional Health Authority were surveyed. Isolates that were subjected to plasmid analysis were found to be mainly the "Asian" type in travellers from abroad and their immediate contacts, whereas isolates apparently indigenous in origin were mainly "African" type. The emerging sigmoid curve of yearly incidence, which is apparent for both the country and the region, may indicate that a dynamic equilibrium is being approached in the susceptible core populations. The importance of vigorous contact tracing is underlined by the contrast between the incidence of PPNG strains in the United Kingdom and the larger numbers found in areas where they are hyperendemic and where contact tracing is ineffectual or non-existent.

In-vitro stability of beta-lactam antibiotics to hydrolysis by beta-lactamases of Neisseria gonorrhoeae from Southeast Asia.

Extracts of penicillinase-producing strains of Neisseria gonorrhoeae obtained from several localities in Southeast Asia exhibited similar patterns of relative rates of hydrolysis of benzylpenicillin, ampicillin, carbenicillin, and cephaloridine. Methicillin and oxacillin were not hydrolyzed. The isoelectric point of the beta-lactamase from these strains was 5.38 +/- 0.05, and the molecular weight was approximately 22.5. These properties, as well as the Km values determined for a range of substrates, were the same for the enzyme purified from one of the strains. These observations are consistent with those reported for other gonococcal beta-lactamases of the TEM-1 type. Cefamandole and to a lesser extent, cefoperazone, were also hydrolyzed by these extracts; however, the newer beta-lactam antibiotics piperacillin, cefuroxime, cefoxitin, ceftriaxone, ceftazidime, and moxalactam were stable. These stable compounds had little inhibitory effect on the activity of the enzyme toward benzylpenicillin or cephaloridine.

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.

Choice of antibiotics and length of therapy in the treatment of acute salpingitis

This article reviews the rationale for the therapy of acute salpingitis and the conceptual basis for the length of therapy. The key to therapy of acute salpingitis is the need to accommodate polymicrobial etiology, polymicrobial bacterial superinfection, and the potential presence of penicillinase-producing strains of Neisseria gonorrhoeae into a therapeutic equation that has been determined by the appropriate staging of disease. The anticipated therapeutic response identified for monomicrobial disease due to Neisseria gonorrhoeae constitutes the end titration point for drug administration. Duration of continued therapy beyond this point Is governed by the need to complete therapy for Chlamydla trachomatis or to assure resolution of advanced disease.

Two regimens of sultamicillin in treating uncomplicated gonorrhoea.

Sultamicillin is a covalent union of ampicillin and the beta lactamase inhibitor, sulbactam (CP-45,899). Two studies were conducted to assess its efficacy in treating uncomplicated gonorrhoea. In the first study treatment comprised sultamicillin 1.5 g and probenecid 1 g; 124 (89.2%) of 139 patients responded including seven of 11 patients harbouring beta lactamase (penicillinase) producing strains of Neisseria gonorrhoeae (PPNG). In the second study sultamicillin 2.25 g and probenecid 1 g were given; 122 (93.8%) of 130 patients responded. Only two of seven pharyngeal infections resolved, and if pharyngeal infections are excluded the overall cure rate rose to 95.3%. Thirteen of 14 patients infected with PPNG strains were cured by the larger dose. Side effects were mild and transitory. It may be concluded that sultamicillin 2.25 g plus probenecid 1 g is an effective regimen to treat uncomplicated rectal and genital gonorrhoea and is useful for treating infections with PPNG strains. Most beta lactamase resistant antimicrobials must be given parenterally; sultamicillin is given by mouth.

In vitro activity of temocillin against Neisseria gonorrhoeae including penicillinase-producing strains.

169 penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) isolated in the United Kingdom were examined for susceptibility to temocillin and spectinomycin. A further 25 PPNG strains and 214 non-penicillinase-producing strains were examined against temocillin, spectinomycin, amoxycillin, cefuroxime and penicillin. Minimum inhibitory temocillin concentrations ranged from 0.36 to 5.0 mg/L with a mode at 1.25 mg/L. The distributions of sensitivities to other agents were in keeping with those previously described.

Treatment of gonorrhea with single-dose thiamphenicol in Kenya.

The efficacy of a single 2.5-g dose of thiamphenicol against infection with penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) or non-penicillinase-producing strains (non-PPNG) was studied in a two-phase clinical trial in Nairobi. The first phase included men who had had a urethral discharge for less than seven days, were infected with either PPNG or non-PPNG, and had not received previous treatment. The second phase included men with PPNG infections that had not responded to treatment with penicillin. The overall cure rate (determined by follow-up examinations and cultures three and ten days after treatment) was 90.6% in the first phase of the study and 92.1% in the second phase. A second 2.5-g dose of thiamphenicol was administered to four of the six patients in the second phase whose cultures yielded gonococci after the initial dose; the infections of all four patients were cured. The results of disk diffusion tests of gonococcal isolates did not correlate well with the outcome of treatment.

Treatment of uncomplicated gonorrhoea in women with a combination of rifampicin and erythromycin.

One hundred women with uncomplicated gonorrhoea (in five cases due to penicillinase producing strains of Neisseria gonorrhoeae (PPNG)) were treated with a single oral dose of rifampicin 900 mg and erythromycin stearate 1 g. N gonorrhoeae was reisolated from the oropharynx of one patient, who was infected with a PPNG strain, but was eradicated from the genital tract in 100% of cases. The combination eradicated Chlamydia trachomatis from only 10 (28%) of the 36 patients infected. Side effects were predominantly mild and consisted of transient nausea. The treatment merits evaluation in areas with a high incidence of PPNG strains.

Ceftriaxone A Review of its Antibacterial Activity, Pharmacological Properties and Therapeutic Use

Ceftriaxone is a new 'third generation' semisynthetic cephalosporin with a long half-life which has resulted in a recommended once daily administration schedule. It is administered intravenously or intramuscularly and has a broad spectrum of activity against Gram-positive and Gram-negative aerobic, and some anaerobic, bacteria. The activity of ceftriaxone is generally greater than that of the 'first' and 'second generation' cephalosporins against Gram-negative bacteria, but less than that of the earlier generations of cephalosporins against many Gram-positive bacteria. Although ceftriaxone has some activity against Pseudomonas aeruginosa, on the basis of present evidence it cannot be recommended as sole antibiotic therapy in pseudomonal infections. Ceftriaxone has been effective in treating infections due to other 'difficult' organisms such as multidrug-resistant Enterobacteriaceae. Ceftriaxone was effective in complicated and uncomplicated urinary tract infections, lower respiratory tract infections, skin, soft tissue, bone and joint infections, bacteraemia/septicaemia, and paediatric meningitis due to susceptible organisms. In most of these types of infections once-daily administration appears efficacious. Results were also encouraging in a few patients with ear, nose and throat, intra-abdominal, obstetric and gynaecological infections, and adult meningitis, but conclusions are not yet possible as to the efficacy of the drug in these indications due to limited experience. A single intramuscular dose of ceftriaxone has been compared with standard therapy for gonorrhoea due to non-penicillinase-producing and penicillinase-producing strains of Neisseria gonorrhoeae and shown to be highly effective. In a few small trials the comparative efficacy of ceftriaxone and other antibacterials has been assessed in other types of infections and in perioperative prophylaxis in patients undergoing surgery. Few significant differences in response rates were found between therapeutic groups in these comparative studies, but larger well-designed studies are needed to more clearly assess the comparative efficacy of ceftriaxone and other antimicrobials, especially the aminoglycosides and other 'third generation' cephalosporins, and to confirm the apparent lack of serious side effects with ceftriaxone. If more widespread use confirms the safety and efficacy of ceftriaxone, it will offer an important alternative, particularly for the treatment of serious infections due to multidrug-resistant Gram-negative bacteria and in situations where the long half-life of the drug could result in worthwhile convenience and cost benefits.

Ophthalmia Neonatorum Caused by β-Lactamase— Producing Neisseria gonorrhoeae

ALTHOUGH infections caused by penicillinase-producing strains of Neisseria gonorrhoeae have been increasing since 1976, 1,2 to our knowledge, there has been to date only one case of ophthalmia neonatorum caused by penicillinase-producing strains of N gonorrhoeae in the United States. 3 A second case of ophthalmia neonatorum caused by penicillinase-producing strains of N gonorrhoeae occurred in a 4-day-old female neonate, who was successfully treated with cefotaxime sodium. Report of a Case A 1,940-g female neonate was born on Sept 11, 1982, to a 34-year-old, para 3, gravida 2, woman by normal spontaneous vaginal delivery at Kings County Hospital, Brooklyn, NY. Apgar scores were 9 at one minute and 10 at five minutes. Estimated gestational age was 36 to 37 weeks. Routine ocular prophylaxis with 1% silver nitrate was given in the delivery room. On the third day of life, the neonate had a copious bilateral conjunctival discharge. Cultures from the