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Biomedical subjects

T M Kerkering

Publications and source records attributed to T M Kerkering.

34 records · Page 2Linked to original sources
PubMed1986

Cefmenoxime kinetics during continuous ambulatory peritoneal dialysis.

The kinetics of the aminothiazolyliminomethoxy cephalosporin, cefmenoxime, were determined after a 30 min intravenous infusion of 15 mg/kg body weight in 6 adult subjects undergoing continuous ambulatory peritoneal dialysis. Concentrations of cefmenoxime in serum, urine and dialysate were determined by high-pressure liquid chromatography. The mean peak serum concentration was 92.8 +/- 11.6 micrograms/ml and the harmonic mean for the elimination half-life was 5.46 h. The volume of distribution at steady-state was 14.60 +/- 3.01 l/kg. Total body clearance of the drug was 31 +/- 7.7 ml/min with 8 +/- 5% and 5.75 +/- 2.72% of the administered dose being eliminated by renal and peritoneal clearance, respectively. Peritoneal clearance for all exchanges (n = 24) was 1.93 +/- 68 ml/min. These data suggest that peritoneal losses of this drug are minimal and doses conventionally employed in advanced renal failure can be utilized in the management of systemic infections.

Adult↗
PubMed1986

Pharmacokinetics and tolerance of ciprofloxacin after sequential increasing oral doses.

The pharmacokinetics and safety of orally administered ciprofloxacin (Bay o 9867) were examined in 12 healthy male volunteers who received sequential doses of 250, 500, 750, and 1,000 mg. The individual and mean data were best described by biexponential disposition and elimination, assuming an apparent zero-order rate of absorption. The peak serum concentrations determined from the individual data occurred at approximately 1.5 h after each dose and ranged from 0.42 to 4.2 micrograms/ml; the mean peak concentrations increased in proportion to the dose. The areas under the curve determined from the mean data were also proportional with respect to dose. The mean elimination half-lives calculated from pooled data were 4.1, 4.1, 6.9, and 6.3 h for doses of 250, 500, 750, and 1,000 mg, respectively. Longer half-lives but proportional area-under-the-curve values after the 750- and 1,000-mg doses implied that smaller fractions of ciprofloxacin were absorbed after these doses, although nonlinear kinetics could not be ruled out. The mean serum concentrations 12 and 24 h following each dose were greater than or equal to 0.08 and 0.01 micrograms/ml, respectively. The urinary concentrations ranged from 30 to 500 micrograms/ml for at least 12 h after administration and were greater than or equal to 9 micrograms/ml at 24 h following each dose. The urinary recovery level of unchanged ciprofloxacin over a 24-h period ranged from 28 to 44%. The mean renal clearances for each dose ranged from 300 to 500 ml/min. Ciprofloxacin was well tolerated, and no significant clinical or laboratory abnormalities were observed.

Adult↗
PubMed1984

In-vitro studies with four new antifungal agents: BAY n 7133, bifonazole (BAY h 4502), ICI 153,066 and Ro 14-4767/002.

Four new antifungal agents were compared in vitro with miconazole and ketoconazole. The agents were BAY n 7133 and ICI 153,066, two orally active triazoles, and bifonazole (BAY h 4502) and Ro 14-4767/002, both topical agents. While all four were found to be broad spectrum antifungal agents they also demonstrated certain gaps in their spectra. In general, Ro 14-4767/002 was the most active agent tested whereas bifonazole and BAY n 7133 were the least active. Noteworthy activities included that of Ro 14-4767/002 against Candida albicans, the dermatophytes and Sporothrix schenckii and that of ICI 153,066 against Torulopsis glabrata.

Antifungal Agents↗
PubMed1984

Spinal cord compression due to an aspergilloma.

Aspergilloma is a common complication of cystic lung disease; it is widely considered to be a saprophytic colonization and local or disseminated invasion is unusual. We describe a patient with stage IV sarcoidosis and bilateral aspergillomas in whom locally invasive disease led to spinal cord compression.

Adolescent↗
PubMed1984

Cefmenoxime pharmacokinetics in patients with renal insufficiency.

The pharmacokinetics of cefmenoxime were determined after a 30-min intravenous infusion of 15 mg/kg of total body weight to 33 adult subjects with normal renal function (CLCR, greater than 80 ml/min per 1.73 m2, group I), mild renal insufficiency (CLCR, 40 to 79 ml/min per 1.73 m2, group II), moderate renal insufficiency (CLCR, 10 to 39 ml/min per 1.73 m2, group III), or severe renal impairment, (CLCR, less than 10 ml/min per 1.73 m2, group IV) or to patients between hemodialysis (CLCR, less than 10 ml/min per 1.73 m2, group V). Concentrations of cefmenoxime in serum and urine were determined by high-pressure liquid chromatography, and serum concentrations were fit to a two-compartment model. There was no significant relationship between creatinine clearance and either peak serum concentrations or volume of distribution at steady state. Patients in group I excreted 81% of the dose into the urine within 24 h; recovery decreased with worsening renal function. The mean terminal half-lives in groups I to V were 1.06, 1.50, 3.55, 4.60, and 11.4 h, respectively. There were good linear relationships between creatinine clearance, and the elimination rate and total body clearance of cefmenoxime. Dosage recommendations for subjects with renal insufficiency are proposed.

Cefmenoxime↗
PubMed1984

Exoantigen test for differentiation of Exophiala jeanselmei and Wangiella dermatitidis isolates from other dematiaceous fungi.

Concentrated (25X) exoantigens of 105 isolates of pathogenic and saprophytic dematiaceous fungi and 3 isolates of Sporothrix schenckii were analyzed by the microimmunodiffusion method. The reagents used were nonadsorbed and adsorbed sera produced in New Zealand rabbits. One set of rabbits was immunized with soluble antigens of a 1-month-old culture of Exophiala jeanselmei (ATCC 34123), and the other set was immunized with soluble antigens from a culture of Wangiella dermatitidis (ATCC 28869). The reference antigens were 25X-concentrated exoantigens of the above cultures. This exoantigen test permitted the differentiation of E. jeanselmei and W. dermatitidis from one another as well as from other Exophiala species, Fonsecaea species, Phialophora species, Cladosporium species, Rhinocladiella species, and Sporothrix schenckii by presence or absence of lines of identity or of partial identity, or lines of nonidentity. Using adsorbed serum eliminated the problems with cross-reactivity seen with nonadsorbed serum. Thus, with an adsorbed serum as the reagent, it was possible to presumptively differentiate E. jeanselmei and W. dermatitidis from one another and from other dematiaceous fungi.

Antigens, Fungal↗
PubMed1983

5-fluorocytosine susceptibility of pathogenic fungi in the presence of allopurinol: potential for improving the therapeutic index of 5-fluorocytosine.

The minimal inhibitory concentration of 5-fluorocytosine in 18 pathogenic fungal isolates was not altered by either allopurinol (100 microM) or oxypurinol (100 microM). Since allopurinol at this level clinically has been demonstrated to interfere with 5-fluorouracil anabolism, thereby reducing toxicity owing to 5-fluorouracil, allopurinol may be useful in counteracting the 5-fluorouracil-induced myelotoxicity observed in patients being treated with 5-fluorocytosine without interfering with the antifungal activity of 5-fluorocytosine.

Allopurinol↗
PubMed1983

Ketoconazole.

The treatment of most fungal infections is difficult, at best. Antifungal therapy is complicated by the development of resistant organisms and by the toxicity of many agents. Ketoconazole, an orally active imidazole derivative, has been approved by the Food and Drug Administration for the treatment of candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. At present, there is very little peer review literature on ketoconazole's effectiveness for several of its approved indications. Gastrointestinal side effects account for the majority of reported adverse reactions; however, preliminary evidence suggests that higher dosages of ketoconazole may decrease adrenal steroidogenesis. Currently, ketoconazole 200-400 mg/d is recommended; the duration of therapy remains to be firmly established. Until well-designed clinical trials are completed and ketoconazole's effectiveness is compared to that of established antifungal agents, its use should be limited.

Antifungal Agents↗
PubMed1982

Isolation of dematiaceous pathogenic fungi from a feed and seed warehouse.

In an epidemiological study, nine isolates of dematiaceous fungi were recovered from the interior of a local feed and seed warehouse. Sample sites include brick walls and floors. Air samples also were included. Samples were collected in saline and plated on Mycobiotic and Sabouraud agar. The nine dematiaceous fungi recovered from these samples were identified with microscopic morphology, thermotolerance, biochemical reactions, and animal virulence test. Four isolates were identified as nonpathogens on the basis of positive gelatin tests. The identified pathogens included Fonsecaea pedrosoi, Cladosporium bantianum (C trichoides), Wangiella dermatitidis (Dixon et al., Mycopathologia 70:153-161, 1980), and Exophiala jeanselmei. These five organisms were injected into NCI/ALB mice. Only the isolate of C. bantianum was neurotropic, as demonstrated histopathologically and by the recovery of the organism from brain tissue. None of the remaining four isolates were seen or cultured from any of the mouse tissues analyzed. The recovery of pathogenic dematiaceous fungi from environmental sites is not uncommon. However, this study is noteworthy in that it represents only the second reported isolation of C. bantianum and the first isolation of F. pedrosoi from the environment in North America and suggests that these fungi may be more ubiquitous in this region that previously believed.

Adult↗
PubMed1982

Blastomycosis.

Blastomycosis is the infection caused by the dimorphic fungus Blastomyces dermatitidis. The fungus was believed to be limited in distribution to North America but is found in Africa and northern South America, too. The exact natural habitat of B. dermatitidis is still uncertain with only rare reported isolation of the fungus from the environment. The inability to recover the organism from nature along with the absence of both a reliable skin test antigen and a sensitive serological test have significantly restricted our understanding of the epidemiology and the full clinical spectrum of blastomycosis. An accidental laboratory infection and several common source epidemics have enabled us to recognize that blastomycosis may be a self-limited pulmonary infection. Endogenous reactivation and opportunistic infections have been newly appreciated as clinical presentations of blastomycosis. This report will review blastomycosis with particular emphasis on these recent developments.

Adult↗
PubMed1981

The evolution of pulmonary cryptococcosis: clinical implications from a study of 41 patients with and without compromising host factors.

Over 14 years 41 patients were diagnosed as having pulmonary cryptococcosis. Cryptococcus neoformans remained localized to the lung in 12 cases and disseminated in the remaining 29. Thirty-four patients were compromised hosts. Disseminated disease developed in 28 of these 34, and four of these 28 patients with disseminated disease presented with concomitant pulmonary and meningeal infections. In all the remaining 24 central nervous system involvement developed 2 to 20 weeks after the finding of an abnormal chest roentgenogram. Seven patients were normal hosts, and in six of these cases disease remained localized to the lung. Four important conclusions were drawn from this study: pulmonary cryptococcosis is rarely considered in the differential diagnosis of an abnormal chest roentgenogram, thereby leading to missed diagnoses and therapeutic errors; the natural history of untreated pulmonary cryptococcosis in compromised hosts is extrapulmonic dissemination; compromised hosts with pulmonary cryptococcosis should receive antifungal therapy because of a high propensity for dissemination; and normal hosts in whom dissemination has been excluded generally do not need antifungal therapy.

Adolescent↗
PubMed1979

Detection of candida antigenemia by counterimmunoelectrophoresis in patients with invasive candidiasis.

Because of the difficulty in diagnosis of invasive candidiasis, an assay that makes use of counterimmunoelectrophoresis (CIE) was developed to detect candida antigen. A cell-wall polysaccharide of Candida was extracted with hot formamide, ethanol precipitation, and gel filtration. Rabbit antiserum was tested by CIE against sera from 20 healthy individuals, 15 patients with mucosal candidiasis, and 48 compromised patients with cultures positive for Candida. Antigen was detected in sera from 13 patients by CIE; eight of these patients were eventually proven to have invasive disease. None of the antigen-negative patients for whom autopsy was performed had evidence of invasive candidiasis. Healthy individuals and patients with superficial mucosal candidiasis were also antigen-negative. The detection of candida antigenemia by CIE is specific for invasive disease and serves as a guide in initiation and follow through of antifungal therapy.

Animals↗
PubMed1979

Spontaneous peritonitis due to Hemophilus influenzae in an adult.

Hemophilus influenzae, usually pathogenic in the pediatric population, caused septicemia and peritonitis in the cirrhotic adult described here. Susceptibility to this unusual adult pathogen was perhaps related to liver disease or corticosteroid treatment. This organism has not previously been associated with the syndrome of spontaneous bacterial peritonitis in an adult.

Adult↗
PubMed1978

Comparison of the in vitro antifungal activities of miconazole and a new imidazole, R41,400.

R41,400 is a recently synthesized, water-soluble imidazole. Its antifungal properties were compared in vitro with those of miconazole using an agar dilution procedure and 175 isolates of human fungal pathogens. The filamentous forms of Histoplasma capsulatum and Blastomyces dermatitidis were inhibited by less than or equal to 2 microgram of either drug/ml; Coccidioides immitis was inhibited by less than or equal to 0.5 microgram of R41,400/ml. Among the yeasts tested, Cryptococcus neoformans and Candida parapsilosis were the most susceptibel to the two drugs, whereas Candida albicans and Candida tropicalis were the least susceptible; 0.5 microgram of either drug/ml was inhibitory for 90%-100% of tested isolates of C. neoformans but for only less than or equal to 20% of isolates of C. albicans, C. tropicalis, and Torulopsis glabrata. Both drugs were inhibitory for most isolates of Trichophyton and Microsporum species at concentrations of less than or equal to 4 microgram/ml; Epidermophyton floccosum was uniquely susceptible to both drugs.

Antifungal Agents↗