J. H. T. Wagenvoort

tetM- and beta-lactamase-containing Neisseria gonorrhoeae (tetracycline resistant and penicillinase producing) in The Netherlands.

Recently, Neisseria gonorrhoeae strains in the United States that were highly resistant to tetracycline (TRNG; MIC, 16 to 64 pugIml) were shown to carry the streptococcal tetM determinant on a 25.2-megadalton (MDa) plasmid (2). The plasmid arose from the insertion of the tetM determinant into the 24.5-MDa gonococcal conjugative plasmid (2, 3). In the spring of 1985, a microepidemic of high-level-tetracycline-resistant, 3-lactamase-positive strains of N. gonorrhoeae was observed in The Netherlands. Twelve strains were isolated, including ten strains from The Hague, one from Rotterdam, and one from Amsterdam. The patient from Rotterdam acquired his infection in The Hague. All the strains were tetracycline resistant (MIC, 16 to 32 ,ugIml), belonged to the auxotype/serotype class Proto/IB-4, and carried the 3.2-MDa P-lactamase plasmid and a 25.2-MDa plasmid. The identical phenotypic characteristics suggested the microepidemic was caused by the spread of a single clone. We examined one of the TRNG/PPNG (penicillinaseproducing N. gonorrhoeae) strains from The Hague and showed by Southern blot analysis that this strain carries tetM on the 25.2-MDa plasmid. The restriction map of this plasmid is similar to those of plasmids isolated from TRNG strains from the United States (1, 2). The tetM determinant appears to be on a same-sized fragment in both the Netherlands and U.S. plasmids. TRNG strains isolated in the United States in 1985 belonged to 18 auxotype/serotype classes; 53% belonged to the Pro-/IB-1 class (1). Three TRNG/PPNG isolates carrying the 3.2-MDa ,B-lactamase plasmid were identified; two belonged to the Proto/IA-1 class, and one belonged to the Proto/IA-2 class. In contrast, the Netherlands isolates belonged to the Proto/IB-4 class. This class was not identified in the U.S. TRNG isolates in 1985. Because the European strain differs from those isolated in the United States during the same period, it is unlikely that this strain spread directly from the United States to The Netherlands. Since the microepidemic, one TRNG and four TRNG/PPNG strains have been identified in The Netherlands. These strains belonged to auxotype/serotype classes other than Proto/IB-4. Thus, we hypothesize that the TRNG/PPNG isolates in The Netherlands may have been imported from an alternative geographic source. This may also be the source of the TRNG isolates identified in the United States. It is also possible that these TRNG strains arose de novo in the United States and The Netherlands. Because all of the TRNG/PPNG isolates possess the 3.2MDa ,B-lactamase plasmid, it appears that these strains did not emerge in the Far East but in a geographic area in which PPNG strains possessing this plasmid are endemic (Africa, Europe, the Caribbean, or the United States). The microepidemic in The Netherlands suggests that TRNG strains are not confined to the United States and provides indirect evidence to suggest that the origin of TRNG strains may not be the United States.

Tinea capitis in The Netherlands (Rotterdam area)

This retrospective study reviews the occurrence and treatment of various forms of tinea capitis at the out‐patient clinic for Dermatology and Pediatric Dermatology of the University Hospital Sophia/Dijkzigt over the period 1977–1988. Tinea capitis was diagnosed in 64 children. Trichophyton violaceum was the pathogen most frequently isolated, with Microsporum canis ranking second. The potassium hydroxide preparation was positive in 58 % of the cases. Four cases showed a positive potassium hydroxide preparation with a negative culture. Immigrant children from Morocco were the largest group (61 %). A zoophilic dermatophyte was isolated in 15 cases (27 %). A pet animal was the source of infection in 4 cases. The ratio between boys and girls was equal in the patient population studied. In 43 % of the children suffering from tinea capitis the clinical features were mild flaking without hair loss (so called seborrheic dermatitis‐like infection).

Comparative double-blind study of 200- and 400-mg enoxacin given orally in the treatment of acute uncomplicated urethral gonorrhea in males.

In a double-blind randomized study, 155 male patients with uncomplicated urethral gonorrhea were given 200 mg (one capsule with 200 mg and one capsule with placebo; n = 77) or 400 mg (two capsules with 200 mg; n = 78) of enoxacin orally. The cure rates in the 200- and 400-mg treatment groups were 90 and 92%, respectively. The enoxacin MIC for the isolated Neisseria gonorrhoeae strains ranged from 0.015 to 0.12 microgram/ml. Postgonococcal urethritis was diagnosed in 29 (42%) patients in the 200-mg treatment group and 19 (26%) patients in the 400-mg treatment group. Side effects (nausea, headache, and vomiting) occurred in 2 (3%) of the 77 patients in the 200-mg treatment group and in 3 (4%) of the 78 patients in the 400-mg treatment group.

Clinical efficacy of ciprofloxacin versus doxycycline in the treatment of non-gonococcal Urethritis in males

In a randomised study the clinical efficacy of ciprofloxacin was compared with that of doxycycline administered in two different dosage schemes to male patients suffering from non-gonococcal urethritis. Fourteen days after completion of therapy (day 21) pyuria was absent in 30 of 100 patients in the ciprofloxacin group;Chlamydia trachomatis was isolated from five andUreaplasma urealyticum from eight patients. In the 100 mg doxycycline group (n=60) pyuria was absent in 36 patients (60 %) andUreaplasma urealyticum was isolated from six patients on day 21. In the 200 mg doxycycline group (n=45) pyuria was absent in 18 patients (40 %) andUreaplasma urealyticum was isolated from two patients on day 21. Side-effects were mild and transient in all groups. It is concluded that ciprofloxacin given in a dosage of 1 g for seven days is not effective in the treatment of non-gonococcal urethritis.

In vitro activity of the two new 4-quinolones A56619 and A56620 againstNeisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum andGardnerella vaginalis

The in vitro activity of tetracycline, ciprofloxacin and two recently developed 1-aryl-fluoro-quinolones, A56610 and A56620, was tested against 65 beta-lactamase-negative and 35 betalactamase-positiveNeisseria gonorrhoeaestrains, 12Chlamydia trachomatis,50Mycoplasma hominis,28Ureaplasma urealyticumand 50Gardnerella vaginalisstrains. In the case ofChlamydia trachomatisandMycoplasma hominisboth the MIC and the MBC were determined. The MIC90 of ciprofloxacin forNeisseria gonorrhoeaewas 0.008μg/mland of A56619 and A56620 ⩽ 0.03μg/ml.No difference was observed between the activity against beta-lactamase-negative and beta-lactamase-positive strains. The MIC90 values of ciprofloxacin and A56620 forChlamydia trachomatis, Mycoplasma hominisandUreaplasma urealyticumwere identical, the values being 2μg/ml, 1μg/mland 4μg/mlrespectively. The MIC90 of A56619 forChlamydia trachomatisandUreaplasma urealyticumwas 0.5μg/mland 1μg/mlrespectively. The MBC90 values of the three quinolones forChlamydia trachomatisandMycoplasma hominiswere ⩽ 2μg/ml.The activity of the quinolones againstGardnerella vaginaliswas rather low, the MIC90 being ⩾ 4μg/ml.It is concluded that A56619 and A56620 might be useful for single-dose therapy of gonococcal infections.

Different doses of cefetamet pivoxil (Ro 15-8075) in the treatment of acute uncomplicated gonococcal urethritis in men.

In an open, dose-finding study, a 100% cure rate was observed in patients suffering from uncomplicated gonococcal urethritis who were treated with a single oral dose of either 1.2 g (n = 10), 0.8 g (n = 11), or 0.4 g (n = 10) of cefetamet pivoxil. The MICs of cefetamet for all gonococcal strains ranged from 0.001 to 0.12 micrograms/ml, and the MIC for 90% of the strains tested was 0.008 micrograms/ml. Cefetamet pivoxil was ineffective against Chlamydia trachomatis in 3 of 31 patients. Side effects were minor.

Randomized comparative study of 0.5 and 1 g of cefodizime (HR 221) versus 1 g of cefotaxime for acute uncomplicated urogenital gonorrhea.

Uncomplicated urogenital and concomitant oropharyngeal gonorrhea in 424 male and female patients was treated in a randomized comparative study with 0.5 g of cefodizime (89 men and 54 women), 1 g of cefodizime (87 men and 52 women), or 1 g of cefotaxime (86 men and 56 women). The cure rates were 100% for men and women in the group given 0.5 g of cefodizime, 100% for men and women in the group given 1 g of cefodizime, and 99% for men and 100% for women in the group given 1 g of cefotaxime. The MICs of cefodizime and cefotaxime for the isolate of Neisseria gonorrhoeae ranged from 0.004 to 0.06 micrograms/ml. Chlamydia trachomatis was isolated before treatment in 15% and after treatment in 13% of all patients. Side effects, such as nausea, diarrhea, abdominal pain, genital candidiasis, and pain at the site of injection, developed in 4% of the patients given cefodizime. Side effects, such as vertigo, genital candidiasis, fatigability, and diarrhea, developed in 4% of the patients treated with cefotaxime. In both groups of patients, the side effects were mild and transient. Cefodizime and cefotaxime are safe and effective agents in the treatment of uncomplicated urogenital gonorrhea.

Treatment of uncomplicated urogenital gonorrhoea in women with a single oral dose of enoxacin

One hundred and twenty-three female patients suffering from uncomplicated urogenital gonorrhoea were treated in a double blind randomised trial with either 200 mg enoxacin (one capsule of 200 mg, one of placebo) or 400 mg enoxacin (two capsules of 200 mg). The cure rate in the 46 evaluable patients in the 400 mg group was 100 %, and in the 40 evaluable patients in the 200 mg group 98.7 %. Minor side effects such as nausea, headache and skin rash occurred in three of 109 evaluable patients (2.8 %). The minimum inhibitory concentration of enoxacin for theNeisseria gonorrhoeaestrains isolated varied between 0.03 and 0.12 mcg/ml. Enoxacin would seem to be a very effective drug in the treatment of uncomplicated urogenital gonorrhoea in female patients.

Solid phase enzyme immunoassay for detection of non-complicated cervical infection withChlamydia trachomatis

To evaluate the usefulness of a solid phase enzyme immunoassay for diagnosis of cervical chlamydial infections, cervical smear samples from 246 women were tested using the assay and cell culture. The overall sensitivity of the assay was 67% and the specificity 92.4%. The sensitivity of the immunoassay was 54% in samples with chlamydial culture with less than 20 inclusions per slide. Thus the enzyme immunoassay failed to detect chlamydial infections in nearly half of the patients with a low amount of chlamydial antigen.

Evaluation of an Enzyme Immunoassay for Detection of Chlamydia Trachomatis in Urogenital Specimens

Chlamydiazyme® (Abbott), an enzyme-linked immunoassay (EIA), was evaluated using cell culture on Hela 229 cells as the method of reference. Samples were acquired from 611 female and 280 male patients attending the outpatient clinic for sexually transmitted disease at the University Hospital in Rotterdam, The Netherlands. The prevalences of chlamydia culture-positive female and male patients were 7.8% and 14.4% respectively. The overall sensitivity and specificity values of the EIA were respectively 68.1% and 95.8% in the female and 92.1% and 92.0% in the male population. Samples which were culture-negative but EIA-positive were re-examined by a second direct test (IDEA; Boots Celltech). If the samples from 12 females and 11 males which were negative on culture but positive with both direct tests are considered as failures of cell culture, the sensitivity of the EIA in females almost equalled cell culture (74.6% versus 79.9%) and in males was even higher (93.9% versus 77.6%). Serotyping of the cultured strains revealed that all serovars of Chlamydia trachomatis occurring in this study could be detected by the EIA. The EIA offers a relatively simple and rapid test for diagnosis of C. trachomatis infections in high-risk populations.