CGP 4832, a new semisynthetic rifamycin derivative highly active against some gram-negative bacteria.

CGP 4832 (5) is a new derivative of rifamycin S, showing a very high degree of activity against certain Gram-negative bacteria, with MICs as much as 400 times lower than those of rifampicin. CGP 4832 and rifampicin inhibit DNA-dependent transcription in vitro to a similar extent, which excludes any difference in their effect on the target enzyme. The most plausible explanation for the potent activity of CGP 4832 is that it penetrates into bacterial cells by way of a specific mechanism. This hypothesis is corroborated by the high rate of mutations leading to bacterial strains resistant against CGP 4832.

CGP 9000: a new orally active, broad-spectrum cephalosporin.

CGP 9000, (7-[D-2-amino-2-(1,4-cyclohexadienyl)-acetamido]-3-methoxy-3-cephem-4-carboxylic acid), is a new broad-spectrum cephalosporin antibiotic. Its antibacterial activity in vitro (MIC) is similar, but its bactericidal efficacy superior to that of cephalexin and cephradine. Upon oral administration to mice infected with various bacteria, CGP 9000 is, in general, 2 to 7 times more effective than either cephalexin or cephradine.

Symmetrical peripheral gangrene in disseminated tuberculosis.

We report the case of a 66-year-old man who developed a symmetrical peripheral gangrene (SPG) on both feet during disseminated miliary tuberculosis. Mycobacterium tuberculosis was not only isolated from sputum, gastric juice, and urine, but also from a blood culture. Since a disseminated intravascular coagulopathy was very likely to be excluded, it is possible that the SPG was due to embolization of arterioles by the tubercle bacilli. The literature of SPG is reviewed and the different possible pathogenic mechanisms of SPG, such as hypoxemia, vasoconstriction, primary endothelial damage, and vascular obstruction, are discussed. SPG is another cutaneous manifestation of disseminated tuberculosis.

Rifampicin against experimental listeriosis in the mouse.

The activity of rifampicin was compared with that of tetracycline, ampicillin, penicillin G, chloramphenicol, gentamicin and sulphadiazine in vitro and in experiments on mice infected with various strains of Listeria monocytogenes. Although the minimum inhibitory concentration of rifampicin was not appreciably lower than that of ampicillin, penicillin G and gentamicin, rifampacin was very much more active in vivo than any of these antibiotics. One of the reasons for its greater efficacy may be that it inhibits or destroys intracellular Listeria. In addition, a synergistic effect was observed in vivo when rifampicin was administered in combination with ampicillin or tetracyline. The combined administration of rifampicin with either of these antibiotics should prevent the emergence of rifampicin-resistant Listeria.

[Simple method for preservation of bacteria in small portions (author's transl)]. / Einfache Methode zum Aufbewahren von Bakterienstämmen in kleinen Portionen

A method of maintaining micro-organisms in small portions is described. The microbial suspensions to be preserved are transferred into small PVC tubes, which are then heat-sealed in small segments. Care must be taken to ensure that the segments are not overfull, otherwise the seams may burst upon freezing. The segments are then transferred strainwise to small propylene test tubes for deep-frozen storage in an electric freezer at -90 degrees C or in liquid nitrogen at -195 degrees C. The viability of the micro-organisms thus treated is fully comparable with that obtained by other methods of deep-freezing. A brief account is given of how the micro-organisms can be recultured from these segments. The above method is particularly suitable when periodical subcultures of a large number of strains have to be prepared over a fairly long period of time. The suppliers of the materials used are indicated.

[Frequency of toxic-shock-syndrome-toxin producing strains of Staphylococcus aureus in the Basel region]. / Frequenz von "Toxic-Shock-Syndrome-Toxin" bildenden Stämmen von Staphylococcus aureus in der Region Basel.

An attempt was made to explain the fact that toxic shock syndrome (TSS) is far less often observed among Swiss women than in the USA. To this end, 353 patients were examined for vaginal infection with Staphylococcus aureus, and 131 strains of Staphylococcus aureus of various origins tested for the formation of "toxic shock syndrome toxin one" (TSST-1). In addition, the patients were questioned about the use of tampons for menstrual hygiene. Taking all age groups into consideration, 2.3% of the 353 patients, and 4.8% of those younger than 27 years, were Staphylococcus aureus carriers. 19.8% of the tested strains of Staphylococcus aureus produced TSST-1. Since these figures are comparable with the US statistics, they afford no explanation for the difference in the incidence of TSS. On the other hand, it seems very probable that the much less common use of tampons, especially the highly absorbent variety, could be responsible. It is also possible that TSS is less often recognized and reported in Switzerland.

Antibiotic sensitivity of gonococcal strains isolated from patients in Basel and environs.

During the first 4 months of 1977, 95 different strains of gonococcus were isolated in the out-patient department of the Dermatology Clinic of the University of Basel. These were systemically tested for sensitivity to penicillin G, spectinomycin, thiamphenicol, doxycycline and rifampicin. The MIC values and the diameter of the zones of inhibition were determined. Tests for beta-lactamase production were made. A correlation in the degree of sensitivity was observed between the following antibiotics: penicillin G/rifampicin; penicillin G/thiamphenicol; penicillin G/doxycycline; thiamphenicol/doxycycline; thiamphenicol/rifampicin; doxycycline/rifampicin. The size of the inoculum had little influence on the activity of the substances, except for that of penicillin G against the beta-lactamase-positive reference strains. No beta-lactamase-producing strains were detected amongst the clinical isolates. In the case of penicillin G, there was a correlation between the minimum inhibitory concentration and the inhibition-zone diameter.

Pharmacokinetic comparison of cefroxadin (CGP 9000) and cephalexin by simultaneous administration to humans.

The pharmacokinetic parameters of cefroxadin and cephalexin were compared after simultaneous oral administration of the two cephalosporins to 21 subjects. The influence of the dose, the formulation, and food intake on these parameters was investigated. Both drugs were equally well absorbed from all of the tested formulations; identical percentages of the dose were recovered in the urine in all cases. The elimination half-life of cefroxadin and, consequently, the area under the plasma concentration-time curve were about 10% less than those of cephalexin. Plasma concentrations and cumulative excretion curves of the two drugs were almost superimposable. Food intake had the same effect on both drugs; absorption was slowed, but the amounts absorbed were almost the same as those in fasted subjects.

[Multicenter study on the status of antibiotic and chemotherapy resistance in Switzerland 1979]. / Multizentrische Studie über die Situation der Antibiotika- und Chemotherapeutika-Resistenz in der Schweiz 1979.

In 1979 a three-month multicentre study of resistance of bacteria isolated from humans and animals was carried out in Switzerland with the participation of 22 institutes and laboratories. A total of 23,852 antibiograms were evaluated concerning the following bacteria: Escherichia coi, Klebsiella pneumoniae, Salmonella sp., Serratia marcescens, Proteus (indole-negative), Proteus (indole-positive), Pseudomonas aeruginosa, Staphylococcus aureus, and enterococci (streptococci of Group D). 95.5% of the strains were isolated from human material, almost half being isolated from urine. The remaining 4.5% were obtained from animal material, more than half being isolated from the milk of cows with mastitis. Although the various institutes and laboratories did not use a uniform, standardized method, the results are closely in line with those of similar studies carried out earlier in Switzerland, Germany, Austria and the USA. No pronounced trend in the direction of increased resistance is observable.

Antimicrobial spectrum of triclosan, a broad-spectrum antimicrobial agent for topical application. II. Comparison with some other antimicrobial agents.

The antimicrobial activity of 5-chloro-2(2,4-dichlorophenoxy) phenol (triclosan, one of the active ingredients of Logamel, Ciba-Geigy) was compared in vitro with that of other antimicrobials exclusively or occasionally used as topical agents in dermatology: hexachlorophene, clioquinol, chlorquinaldol. gentamicin, neomycin, nystatin, econazole, clotrimazole and salicylic acid. Upon determination of the MICs for 53 strains of aerobic and anaerobic bacteria, yeasts and fungi, triclosan was found to display a high degree of activity against most of the test organisms and to have the broadest spectrum of chemotherapeutically significant antimicrobial activity of the substances tested.

[Contribution to the epidemiology of Campylobacter jejuni. From asymptomatic excretion by a cow in the cowshed to overt disease in over 500 persons]. / Beitrag zur Epidemiologie von Campylobacter jejuni. Von der asymptomatischen Ausscheidung im Stall zur Erkrankung bei über 500 Personen.

An outbreak of C. jejuni enteritis involving participants of a jogging rally is described. Information was obtained by questionnaire about food consumption, incubation period, duration of illness and symptomatology. A drink prepared with raw milk was incriminated as vehicle of the outbreak. More than 500 runners were symptomatic with an attack rate of over 75%. Secondary cases were rare. Using serotyping, milk from a single cow fecally excreting C. jejuni type 2 was suspected to be the outbreak vehicle.

Pharmacokinetics of clofazimine in healthy volunteers.

The pharmacokinetics of clofazimine was evaluated in 12 healthy male volunteers following single and multiple oral doses of clofazimine. Six volunteers received a single dose of 200 mg together with food. A 200-mg dose was administered to three volunteers either with or without food. In a multiple-dose experiment, three volunteers were repeatedly dosed with 50 mg per day together with food for 8 days. Following a single oral dose of 200 mg, the mean peak plasma concentration of clofazimine was 861 +/- 289 pmol/g (+/- S.D., N = 6) after 8 hr (median). The mean terminal half-life was 10.6 +/- 4.0 days. Comparison of the bioavailability of clofazimine administered with or without food revealed a 60% higher mean area under the curve (AUC) value and a 30% higher mean maximum concentration (Cmax) value with food (N = 3). The median of times to peak (Tmax) was 8 hr with food and 12 hr without food. In the multiple-dose study, good agreement was found between the mean experimental plasma concentration values and the plasma concentration profile predicted from the single-dose pharmacokinetics. The elimination half-life calculated from the terminal phase of the individual profiles after the last dose was 8.8 +/- 1.0 days (+/- S.D., N = 3). The half-life obtained from the fitted mean multiple-dose profile was 10.5 days. The slow elimination of clofazimine has its implications for the treatment regimen in patients. To avoid the long-lasting accumulation toward the steady state, higher daily loading doses are recommended at the beginning of therapy followed by a daily maintenance dose.

Diagnosis of bacterial overgrowth after culturing proximal small-bowel aspirate obtained during routine upper gastrointestinal endoscopy.

The purpose of this study was to evaluate the method of obtaining aspirated fluid for culture from the small intestine through a fiberoptic gastrointestinal endoscope for diagnosing small-bowel overgrowth. The study population consisted of 10 healthy volunteers and 26 patients with various gastrointestinal problems referred for routine endoscopic examination. The material to be cultured was obtained under direct visualization approximately 25 to 30 cm distal to the pylorus or from the afferent loop (in Billroth-II patients) with a sterilized sheathed wash pipe passed through the suction channel of the endoscope. Cultures were considered positive for bacterial overgrowth if total counts of organisms were 10(5)/ml or more. All healthy volunteers and 16 of 21 unoperated patients had sterile or insignificant growth, whereas all 5 patients who had Billroth-II operations had positive overgrowth. The endoscopic method for collection of proximal gastrointestinal fluid for culture is simple and can be performed during routine endoscopy.

[Standardized disk tests for the determination of bacterial resistance ]. / Standardisierte Blättchentests zur Resistenzprüfung von Bakterien.

This paper describes the standardized Kirby-Bauer disc method for the determination of antibacterial susceptibility, also including choice of antimicrobials, interpretation of results, problems with particular bacteria, and quality control. Only a meticulous adherence to the details of the method will guarantee reliable results.

Etiology of acute infectious diarrhea in a highly industrialized area of Switzerland.

During an 18-mo period between 1981 and 1982, a prospective study was conducted in 119 adult patients with acute diarrhea. A diarrhea-inducing microorganism or toxin could be identified in 38.7% of the patients. Salmonella sp and Campylobacter jejuni were the leading agents that caused diarrheal illness in 25% of the investigated population. Clostridium difficile was found in 6%, mainly after previous antibiotic therapy. Rotavirus was rarely isolated and enterotoxigenic Escherichia coli were not found. Clinical features in patients in whom an invasive agent was isolated did not differ from those in patients in whom no enteropathogens were found, although the occurrence of fecal leukocytes and positive hemoccult tests in the former group was significantly more frequent. More than 30% of the patients with negative stool cultures, however, showed fecal leukocytes and positive occult blood, which is suggestive of the existence of one or more invasive agent(s) so far unknown or not recognized.

Helicobacter pylori infection in healthy people: a dynamic process?

Epidemiological studies using serological tests have shown that a large proportion of healthy people have antibodies against Helicobacter pylori (anti-Hp). It is uncertain whether the presence of anti-Hp indicates active infection or only past exposure to the micro-organism. In this study we determined anti-Hp with a specific enzyme linked immunosorbent assay in 100 healthy volunteers who were at the same time investigated for active H pylori infection by means of the 13C-urea breath test. Forty nine per cent had a high anti-Hp titre, but only 24% had active H pylori infection. Our study suggests that a considerable number of healthy people previously infected with H pylori have spontaneously eliminated this microorganism. We suggest that the inability of ulcer patients to eliminate H pylori may be important in the pathogenesis of peptic ulcer disease.