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Biomedical subjects

H C Korting

Publications and source records attributed to H C Korting.

At least 217 records · Page 12Linked to original sources

Evaluation of cefotetan in uncomplicated gonorrhea.

Cefotetan is a newly developed cephamycin especially resistant to bacterial beta-lactamase. Therefore both its in vitro activity against Neisseria gonorrhoeae and its clinical efficacy in uncomplicated gonorrhea are investigated. The minimal inhibitory concentrations (MIC) lie in the range of 0.016-2 micrograms/ml, 90% of the strains being inhibited by 0.5 microgram/ml. Of 52 finally evaluable patients who were treated by a single intramuscular injection of 1 g, 48 (92.3%) were cured bacteriologically. Thus the present treatment protocol may prove useful in individual cases. It should, however, not be advocated for gonorrhea treatment in general.

Adult↗

[Pathogen-host relations in sexually transmitted diseases].

The host-parasite relationship between the major causative agents of sexually transmitted diseases, e.g. Neisseria gonorrhoeae, Treponema pallidum and Trichomonas vaginalis, and their target cells in the urogenital tract can generally be studied in suitable cell and organ cultures. Experience with N. gonorrhoeae predominantly gained from fallopian-tube organ cultures shows that there are several prerequisites for adherence as the first step of pathogenesis. They range from the type of bacterial pili to the type of epithelial cell. Later the function of these cells is damaged by subcellular toxins of a lipopolysaccharide nature. The cocci are phagocytosed, which eventually leads to definite (ultra-) structural alterations. These processes are not only described in detail but also compared with those found with other bacterial species and target cells. Possible predisposing factors in the host are also taken into account. Finally the need for investigating the effect of antibiotics on the host-parasite relationship is stressed.

Animals↗

[Normal pH value of human skin].

Today, the term "normal skin pH" is understood to be the pH value of the surface of the skin of the lower arm of a healthy adult male Caucasian. Its mean value lies in the range 5.4-5.9. In most cases, it is determined by means of a flat glass electrode. The parameter "skin pH" depends mainly on the area of skin and on age, but it also depends to a lesser extent on sex, race and the time of day when values are determined.

Acid-Base Equilibrium↗

Human plasma and skin blister fluid levels of griseofulvin after its repeated administration.

Griseofulvin was administered orally to 6 healthy volunteers for 6 days. The subjects received 500 mg of a microsize formulation and 330 mg of an ultramicrosize formulation, according to a cross-over design. The drug was determined in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) following the last dose. Urinary excretion of the main metabolites 6-demethylgriseofulvin (6-DMG) and its glucuronic acid conjugate was also measured. The pharmacokinetic parameters were compared with those obtained from a recent single dose experiment. On repeated administration, the bioavailability of griseofulvin was significantly lower from the microsize formulation; the urinary recovery of total 6-DMG was 33.8% versus 53.6% on administration of the ultramicrosize material. Bioavailability was reduced as compared to ingestion of a single dose. The reduction was more prominent following the microsize (36%) than the ultramicrosize (17%) formulation. Penetration into skin blister fluid was not altered as compared to the single dose experiment. Relative areas under the blister fluid-time curves amounted to 51% (SBF) and 80% (CBF) of the area under the plasma level-time curve. The concentration of unbound griseofulvin in these body fluids was identical throughout the entire dosage interval. Unbound griseofulvin levels were low in comparison with the minimum inhibitory concentrations for strains of trichophyton and microsporum.

Blister↗

Human plasma and skin blister fluid levels of griseofulvin following a single oral dose.

Griseofulvin and 6-demethylgriseofulvin (6-DMG) in plasma, suction blister fluid (SBF) and cantharides blister fluid (CBF) and urinary excretion of 6-DMG, were evaluated following administration of single oral doses of an ultramicrosize and a microsize formulation of griseofulvin to 6 healthy volunteers. The bioavailability of griseofulvin was higher following the ultramicrosize formulation when 64% of the dose was recovered (via metabolites) versus 52% after the microsize preparation. Penetration into skin blister fluid was delayed as compared to plasma levels; the peak concentration in plasma was observed at 3-4 h, whereas griseofulvin in CBF increased up to 6 h. The terminal half-live was calculated from plasma levels to 9.3 h. The half-lives calculated from SBF and CBF concentrations were 9.2 and 9.8 h, respectively, (n = 5). In plasma 84% of griseofulvin was bound to proteins, predominantly to albumin; binding in SBF and CBF was 72 and 82%, respectively. 3 h after drug administration the free concentration in plasma significantly exceeded the free concentrations in SBF and CBF. Distribution equilibrium between plasma and skin blister fluid was observed after 27 h. Thus, during chronic administration, the plasma griseofulvin level should reflect its concentration in the target organ.

Administration, Oral↗

Treatment of gonorrhoea with cefotiam: activity in vitro and clinical results of a 1-gram single-dose regimen.

Cefotiam is clearly more active against Neisseria gonorrhoeae in vitro than penicillin. This applies especially to strains producing beta-lactamase but also to those which do not. No strain requires more than 0.25 micrograms/ml for inhibition. 1 g of cefotiam dissolved in 3 ml of 1% lidocaine solution cures 90.0% of patients suffering from uncomplicated genital gonorrhoea if injected once intramuscularly. Tolerance of this regimen is very good, no major side-effect being found.

Cefotaxime↗

Gonoblennorrhoea adultorum (gonococcal conjunctivitis)--a "disappearing disease" which does not disappear.

Gonoblennorrhoea adultorum (GA) still occurs in spite of contrary statements. During the last 10 years, 4 cases were seen in the Munich Clinic of Dermatology (constituting 0.19% of all patients with gonorrhoea). While the conjunctivae alone were involved in 3 of them, in 1 the cornea showed alterations as well. Thus, the disease has not lost its potential danger. Yet the newer cephalosporins seem to cure GA rapidly, even if given in a single dose (together with local treatment).

Adult↗

Preputial abscesses caused by beta-lactamase-producing gonococci.

Preputial abscesses occurred in three men who had had sexual intercourse with prostitutes in Thailand. Neisseria gonorrhoeae could be grown from the lesions. Two of the strains were tested for beta-lactamase production and proved positive. While all three patients showed no clinical signs of urethritis, urethral swabs were positive for gonococci in two.

Abscess↗

[Importance of the auxotyping of Neisseria gonorrhoeae for evaluating gonorrhea therapy studies].

So far, there was no absolutely reliable way to distinguish between failure and reinfection in clinical trials on the treatment of gonorrhoea. If one, however, analyzes the auxotypes of the gonococcal strains isolated before and after application of the drug from non-cured patients, reinfection can clearly be demonstrated in cases with a changed auxotype. Thus, in a trial on the single intramuscular application of cefotiam 1 g for uncomplicated gonorrhoea, the bacteriological cure rate increased from 90 to at least 95%.

Clinical Trials as Topic↗

Plasma and skin blister fluid levels of cefotiam and cefmenoxime after single intramuscular application of 1 g in gonorrhea.

To predict the clinical efficacy of a new antibiotic in uncomplicated gonorrhea, data pertinent to its pharmacokinetics in man are needed. Before starting clinical trials on cefotiam and cefmenoxime, 1 g of each antibiotic was administered intramuscularly as a single dose to 5 healthy volunteers. Both blood and skin blister fluid samples (obtained by suction and cantharides blistering) were repeatedly taken. Peak plasma levels amounted on average to 24.8 and 48.2 micrograms/ml, respectively. 6 h after dose still average plasma concentrations of 3.4 and 6.52 micrograms/ml were found. Suction blister fluid levels essentially paralleled plasma levels, whereas cantharides blister fluid levels increased and decreased more slowly than plasma levels. Cefotiam penetrated more readily into suction blister fluid than cefmenoxime as obtained from area ratios. Thus, the chosen dosage regimens considered apt for gonorrhea led to high initial as well as long-standing drug levels. And this does not only hold true for the plasma. Facing their good in vitro activity on Neisseria gonorrhoeae, cefotiam and cefmenoxime well deserve further studies in this field including clinical trials.

Adult↗

Susceptibility of Neisseria gonorrhoeae to ceftizoxime in vitro and in vivo.

Ceftizoxime - a new beta-lactamase-resistant cephalosporin - was tested for its potential efficacy in the cure of uncomplicated gonorrhea. While more than a half of the 102 freshly isolated Neisseria gonorrhoeae strains examined was partially or totally resistant to penicillin (MIC greater than or equal to 0.06 microgram/ml), most of these strains proved highly susceptible to ceftizoxime (as well as cefotaxime). The MIC90% amounted to 0.004 micrograms/ml, while serum levels after the intramuscular application of as little as 0.5 g exceed 1 microgram/ml for more than 6 h. The clinical results were excellent. 105 male or female patients suffering from uncomplicated gonorrhea were treated with a single intramuscular application of 1 g of ceftizoxime. 61 of them reattended our clinic twice for follow-up. All of them were cured. Anaphylactic shock or rashes were not observed. Thus, we consider the intramuscular application of 1 g of ceftizoxime as a reliable and safe treatment for uncomplicated gonococcal urethritis and cervicitis.

Adolescent↗

Repeated exposition to subinhibitory concentrations of antibiotic in vitro readily decreases susceptibility of Neisseria gonorrhoeae to rifampicin, but not to new cephalosporins and penicillin G.

Repeated subcultivation of Neisseria gonorrhoeae in the presence of subinhibitory concentrations of antibiotic has turned out as a reliable model to predict the low potential for development of resistance with respect to the beta-lactam antibiotic penicillin. Before large-scale introduction of the new cephalosporins we exposed 5 N. gonorrhoeae strains of different susceptibility to penicillin repeatedly to subinhibitory concentrations of cefotiam, ceftizoxime, rifampicin and penicillin G incorporated into chocolate agar. each time the most resistant representatives of a strain were propagated, on the whole 25 times. While resistance to rifampicin increased readily (all strains became relatively resistant, MIC = 4 micrograms/ml), the same was not true of the cephalosporins. Although their susceptibility decreased, too, no strain acquired partial or even total resistance (final MIC less than or equal to 0.128 with cefotiam and ceftizoxime). The cephalosporins thus rather parallelled penicillin G which hardly induced any increase of resistance. Thus, a quick loss of clinical efficacy need not be feared after large-scale introduction of the new cephalosporins into the therapy of gonorrhea.

Anti-Bacterial Agents↗

In vitro susceptibility of recent isolates of Neisseria gonorrhoeae to cephalosporins of different generations and penicillin G: a comparative evaluation.

98 recent clinical isolates of Neisseria gonorrhoeae (96 nonpenicillinase-producing N. gonorrhoeae (NPPNG) and 2 penicillinase-producing N. gonorrhoeae (PPNG) strains) were tested for their antibiotic susceptibility using the agar dilution test. The antibiotics examined all belonged to the beta-lactam group: penicillin G represented the penicillins, cephalothin, cefazolin, cefotiam, cefmenoxime and ceftizoxime represented the different groups of cephalosporins. In the in vitro tests cephalothin and cefazolin proved less active than penicillin G, cefotiam a bit more and both cefmenoxime and ceftizoxime much more active. These last three antibiotics should become promising alternatives to penicillin in the therapy of gonorrhea caused either by NPPNG or PPNG strains.

Cephalosporins↗

Ketoconazole concentrations in human skin blister fluid and plasma.

To investigate ketoconazole penetration into skin, a single oral dose of 200 mg was administered to six healthy subjects. Plasma and cantharides blister fluid (CBF) levels were measured for 11 to 24 hours. In suction blister fluid (SBF) ketoconazole was determined 3, 6, and 9 hours after administration. Mean peak plasma levels of ketoconazole were found at 1 hour, they amounted to 3.03 +/- 0.55 micrograms/ml (n = 5). Apparent half-life of elimination was 1.8 hours. In cantharides blister fluid maximum ketoconazole concentrations were obtained at 6 hours being 1.05 +/- 0.32 micrograms/ml and declined rather slowly (half-life 4.2 hours; n = 3). Maximum concentrations in suction blister fluid were obtained 3 hours after administration (0.914 +/- 0.123 micrograms/ml). After 9 hours ketoconazole levels had declined to 0.216 +/- 0.044 micrograms/ml (n = 3). These concentrations exceed the ketoconazole concentrations proven to be effective in vitro up to 25 fold.

Adult↗

Plasma, cantharides blister fluid, and suction blister fluid levels of ceftizoxime after single intramuscular application for gonorrhea.

Following a single intramuscular application of 1 g ceftizoxime, levels of the drug were determined in plasma as well as in suction blister fluid (SBF) and cantharides blister fluid (CBF). This regimen invariably led to both high and long-lasting plasma levels: 81 +/- 16 min post dose maximum plasma levels of 17.5 +/- 3.1 micrograms/ml were reached; 6 h post dose levels of 4.6 +/- 0.4 micrograms/ml were still found, i.e., 4375 and 1150 times, respectively, the MIC90% of Neisseria gonorrhoeae. The high plasma levels were parallelled by high concentrations in SBF, with peaks amounting to 8.4 +/- 1.0 micrograms/ml. Peak concentrations in CBF ranged from 8.1 to 15.7 micrograms/ml. Thus, the pharmacokinetic behavior of ceftizoxime given as a single intramuscular injection of 1 g explained the excellent clinical results of this regimen in uncomplicated gonorrhea.

Adult↗

[Cephalosporin allergy and cephalosporin-penicillin cross allergies with special reference to venereologic therapy of severe anaphylactic reactions].

The newer cephalosporins are gaining more and more importance in antimicrobial chemotherapy. This also applies to venereology. Yet before widespread use, their potential for anaphylactic reactions must be defined, as they are not uncommon with penicillin. In fact, the first cephalosporins shared this drawback with penicillin. According to the experimental and clinical data available, the newer cephalosporins, however, should not give rise to severe allergic reactions of the immediate type. This at least holds true for individuals without a history of allergy to beta-lactam-antibiotics but, in fact, not even they should be endangered. This, however, still needs further confirmation.

Anaphylaxis↗