摘要:

The disposition kinetics of ofloxacin, a quinolone antibacterial agent excreted essentially unmodified by the kidney, was studied after single oral administration in 8 patients with compensated liver cirrhosis and in 8 control subjects. Mean elimination half-life and apparent volume of distribution were significantly increased in the cirrhotic group (7.6 vs. 4.9 h and 1.6 vs. 1.2 liters kg-1, respectively). A reduction in the renal clearance of ofloxacin was also observed in the cirrhotic patients, in spite of an apparently normal renal function. These observations indicate that also the pharmacokinetics of unmetabolized drugs may be altered in compensated liver cirrhosis. The serum concentration-time profiles of nearly all subjects exhibited a secondary peak 4-6 h after dosing. This double-peak behavior was interpreted as either enterohepatic circulation or biphasic gastric emptying of ofloxacin.

ISSN:0009-3157    

DOI:10.1159/000238934

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Itraconazole is a lipophilic triazole with potent in vitro activity. It is also effective after topical, oral and parenteral administration. The antifungal activity of itraconazole has been evaluated against more than 6,500 different strains, belonging to more than 260 fungal species, using the serial decimal dilution test in fluid broth medium (brain-heart infusion broth). Candida spp., Torulopsis spp., Cryptococcus neoformans, Pityrosporum spp. (Dixon broth), various other yeasts, dermatophytes, Aspergillus spp., Penicillium spp., Sporothrix schenckii, dimorphic fungi (mycelium phase and yeast phase), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive. Most strains of Fusarium and Zygomycetes are poorly sensitive. Itraconazole was administered orally and parenterally in normal and immunocompromised guinea-pigs infected with C. albicans, Cr. neoformans, Histoplasma duboisii, S. schenckii, P. marneffei and A. fumigatus. It was effective in terms of both survival of the animals and elimination of the fungi from the various tissues. Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, and to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis. No comparative studies have yet been undertaken for other deep mycoses. The results of combination therapy with itraconazole and fluconazole in cryptococcosis were indifferent; with flucytosine or amphotericin B, additive or synergistic effects were seen in systemic candidosis, cryptococcosis and aspergillosis. No drug-related side-effects were observed after oral or parenteral administration of itraconazole.

ISSN:0009-3157    

DOI:10.1159/000239046

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

A new method of data presentation that takes into account the relationship between growth and killing rate was used to evaluate the comparative in vitro bactericidal activity of cefpodoxime, cefuroxime, cefixime and an amoxicillin/clavulanic acid combination against Streptococcus pneumoniae and β-lacta-mase-producing strains of Haemophilus influenzae and Moraxella catarrhalis. For each strain, the viable count decrease (log CFU/ml) after 6 h of exposure to different antibiotic concentrations was plotted against the viable count increase in the control culture, over the same time. Higher killing rates than those predicted by growth rates were defined as a positive balance; lower rates than those predicted by growth rates were defined as a negative balance. The activity of the 4 drugs against S. pneumoniae and M. catarrhalis was characterized by a positive balance. Conversely, the 3 cephalosporins showed a negative balance for H. influenzae.

ISSN:0009-3157    

DOI:10.1159/000238935

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Itraconazole has emerged as an important new oral agent in the treatment of systemic fungal infections. This paper summarizes the data available on its use in aspergillosis, cryptococcosis and histoplasmosis, compiled in the United States with particular attention to the immunocompromised host. Data have been accrued in open-label studies including 57 patients with cryptococcal disease where the overall response rate among patients with meningitis was 86%, and in 28 patients (8 with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection) with invasive aspergillosis where the overall response rates were 80% in patients without AIDS and 86% in patients with AIDS. Data are summarized on 6 patients with allergic bronchopulmonary aspergillosis, 5 of whom demonstrated marked improvement on therapy, and 12 patients with histoplasmosis including 8 with AIDS, 11 of whom responded and 1 recrudesced on therapy. In summary, itraconazole showed activity in human studies of aspergillosis, cryptococcosis and histoplasmosis with minimal toxicity. Itraconazole offers a new oral alternative to conventional amphotericin B therapy in these infections. Comparative studies are needed to clarify its role.

ISSN:0009-3157    

DOI:10.1159/000239048

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Cefuroxime and cefonicid, two common representatives of the second-generation cephalosporins, were compared for their spectrum of activity against 1,000 isolates of gram-negative Enterobacteriaceae. Cefuroxime had an overall advantage of 6.3% over cefonicid. Upon investigation, we found that this was mainly due to Escherichia coli: 11.2% of the E. coli strains proved resistant to cefonicid whilst only 0.4% were cefuroxime resistant.

ISSN:0009-3157    

DOI:10.1159/000238936

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Cefuzonam [CZON, sodium (-)-(6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-[(1,2,3-thiadiazol-5-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylate] is a newly developed semisynthetic cephem with a broad antibacterial spectrum. The effects of CZON on peptidoglycan cross-linking reactions were examined in Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa. The cross-linking enzyme(s) from P. aeruginosa was the most susceptible to CZON, although the bacterium was resistant to CZON. CZON was active against S. marcescens in spite of its weak inhibitory activity against the enzyme(s) from the bacterium.

ISSN:0009-3157    

DOI:10.1159/000238937

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

In this paper the bactericidal activities of ofloxacin and its optically active derivative, DR-3355, against non-growing cells of Escherichia coli and Pseudomonas aeruginosa are described. E. coli and P. aeruginosa were killed rapidly by ofloxacin and DR-3355. After treatment with these quinolones, the resting cells of E. coli and P. aeruginosa became plasmolyzed, with apparent cytoplasmic shrinkage without filamentation. Membrane-bound intracellular vacuoles and disruption of the cell envelope were also observed, resulting in extrusion of the cytoplasmic contents. These results indicate that non-growing cells of E. coli and P. aeruginosa were susceptible to ofloxacin and DR-3355, as were logarithmically growing cells.

ISSN:0009-3157    

DOI:10.1159/000238938

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Treatment of fungal infections in neutropenic patients continues to be a major problem for the clinician. Treatment of such infections with amphotericin B is difficult, because of its many side-effects. In a neutropenic mouse model, itraconazole appeared to be as effective as amphotericin B against Candida albicans, and was more effective than amphotericin B in treating an Aspergillus infection in a patient with chronic granulomatous disease. In a randomized, comparative trial of itraconazole and amphotericin B as treatment for Candida and Aspergillus infections, 32 neutropenic patients were evaluated. Patients received either oral itraconazole, 200 mg twice daily, intravenous amphotericin B, 0.6 mg/kg/day, or in some cases of Candida infection intravenous amphotericin B, 0.3 mg/kg/day, plus flucytosine, 150 mg/kg/day. The causative organism of fungal infection was Candida spp. in 16 patients and Aspergillus spp. in 13 patients; 27 patients had pneumonia. The median duration of treatment was 13 days with amphotericin B and 20 days with itraconazole. Nine of 16 patients responded to amphotericin B, and 10 of 16 patients responded to itraconazole. Of the patients with Aspergillus infection, 6/8 treated with itraconazole and 2/5 treated with amphotericin B responded. Three patients with Aspergillus infection died in the amphotericin B arm and none in the itraconazole arm; 2 patients treated with itraconazole died from candidal infections. Absorption of itraconazole was unreliable in these seriously ill patients with disturbed gastrointestinal function. These results suggest that itraconazole could be an effective drug against systemic fungal infections in neutropenic patients. One retrospective study also suggests that itraconazole is superior to ketoconazole in prophylaxis for Aspergillus infections. Further studies are needed.

ISSN:0009-3157    

DOI:10.1159/000239049

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The most common tropical subcutaneous and deep mycoses include chromomycosis, sporotrichosis and mycetoma. All are commonly found in Natal and in other subtropical countries. Although blastomycosis is endemic in North America, only 4 cases have been identified in Natal during the last 25 years, and all presented with atypical clinical features. African histoplasmosis, caused by Histoplasma capsulatum var. duboisii and limited mainly to central and western Africa, has been found in only 1 patient in Natal. Paracoccidioidomycosis, though the most common deep mycosis in Latin America, is limited to that area and there is no experience of this disease in South Africa. Over the past 8 years, itraconazole has been used in clinical trials for all 3 mycoses. The results in sporotrichosis, non-meningeal blastomycosis and paracoccidioidomycosis suggest that for these diseases itraconazole may be the drug of choice. The results in histoplasmosis are encouraging, as are the results in chromomycosis, particularly those cases associated with Cladosporium carrionii. Where Fonsecaea pedrosoi is the causal agent and in mycetomas, however, successful management still remains a therapeutic problem. Enhanced efficacy by combining flucytosine and itraconazole was seen in 3 patients. Even over prolonged periods, itraconazole has an impressive safety profile. In the present series of 41 patients, no side-effects were observed, no adverse reactions occurred, and serum chemistry values remained within normal limits. It appears, therefore, that itraconazole, though not the final answer to management of deep mycoses, is certainly a major improvement on previous drugs.

ISSN:0009-3157    

DOI:10.1159/000239050

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We measured the sizes of the inhibition zones of oral β-lactam antibiotics for Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae in the presence of β-lactamase-producing-Moraxella (Branhamella) catarrhalis by the agar double-layer method. The sizes of the zones of amoxicillin for S. pneumoniae alone were the largest, followed in a descending order by those of cefixime and cefaclor. In the presence of 107 CFU/ml of M.(B.) catarrhalis, however, significant reduction of the sizes of the zones was seen with amoxicillin and cefaclor; inhibition with cefixime was nearly unchanged. Similar results were observed in those for S. pyogenes. These variable findings were attributed to the difference in stability of these drugs to the β-lactamase produced by M. (B.) catarrhalis. When the susceptibility of H. influenzae in the presence of 108 CFU/ml of M.(B.) catarrhalis to cefixime, cefoteram, cefpodoxime, cefotiam and cefuroxime was examined, the sizes of the inhibition zones of all the drugs were reduced by the presence of 108 CFU/ml of M.(B.) catarrhalis, but those of cefixime were the largest of all the drugs tested. Our agar double-layer method is simple and useful for evaluating the influence of β-lactamase-producing organism, as M. (B.) catarrhalis, on the disk susceptibility of other pathogens to antibiot

ISSN:0009-3157    

DOI:10.1159/000238939

出版商:S. Karger AG    

年代:1992

数据来源: Karger