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Biomedical subjects

C Carbon

Publications and source records attributed to C Carbon.

At least 109 records · Page 6Linked to original sources

Increased intestinal absorption of cefixime by nifedipine in the rat intestinal perfusion model: evidence for a neural regulation.

In healthy volunteers, the simultaneous administration of nifedipine and cefixime has been shown to increase the oral absorption of the antibiotic. To investigate the pharmacological basis of this interaction, we used an in situ intestinal perfusion technique in the rat. pH 5.5 yielded optimum cefixime absorption, which was greater in segments from the duodenojejunum than in those from the jejunoileum. Cefixime absorption was similar when perfused at 0.5 and 1.0 mg/ml, suggesting transport saturation at the lower concentration. Cefixime arterial and portal blood concentrations after an intestinal perfusion of 0.5 mg/ml cefixime were significantly increased by a previous 15-min intestinal perfusion of 0.05 mg/ml nifedipine. Nifedipine did not significantly alter intestinal blood flow. At the end of the cefixime perfusion, intestinal blood flow was higher in the nifedipine group than in the control group (0.44 +/- 0.12 vs. 0.26 +/- 0.09 ml.min-1.g of intestine wt-1, respectively), although the difference did not reach statistical significance. The absorption kinetics of salicylic acid, which is strictly absorbed by passive diffusion, were unaffected by nifedipine. After 15 and 50 min of recirculation, residual salicylate levels fell from 85.1 +/- 5.6% to 57.1 +/- 2.8% with nifedipine compared with 87.4 +/- 1.4% to 52.8 +/- 1.6% without nifedipine. Thus, the improvement in cefixime absorption by nifedipine was not secondary to increased local blood flows or to induced passive diffusion mechanisms. Nifedipine did not affect intestinal motility. The action of nifedipine appears to indirect, involving a neural regulation, because any increase in cefixime absorption was prevented by tetrodotoxin and hexamethonium administration.

Animals↗

[Tuberculosis. Current therapeutics].

Due to the constant decline in incidence up to the mid eighties, eradication of tuberculosis appeared to be an attainable objective in developed countries. Since then multiple factors (HIV epidemic, poor social conditions in certain unfavored areas, population migrations, urbanization) have led to an increased frequency, making an excellent knowledge of tuberculosis a priority for all physicians. Multi-resistant mycobacteria have also made their appearance leading to numerous clinical and experimental studies which provide new insights into the correct management of patients with tuberculosis. Despite these recent changes, the classical treatment for tuberculosis remains the same in most cases, allowing nearly-certain cure when applied correctly in patients infected with a susceptible bacteria, including those with HIV infection or extrapulmonary localizations. On the contrary, the spontaneous aggravation of multi-resistant tuberculosis, even in some cases being treated, emphasizes the need to test the strain's susceptibility to the antituberculous agents used. Certain new antibiotics, including fluoroquinolones, may play an important role in some cases. The contribution of surgery, isolation and strict compliance must also be emphasized. Resistant strains may also led to renewed indications for the Calmette-Guérin vaccine.

AIDS-Related Opportunistic Infections↗

Lymphocyte subset counts during the course of community-acquired pneumonia: evolution according to age, human immunodeficiency virus status, and etiologic microorganisms.

We investigated the evolution of lymphocyte subsets in blood samples from 94 consecutive patients with community-acquired pneumonia; these samples were obtained 72 hours after hospitalization and at follow-up, when the patients were considered to be cured. Acute-phase lymphocyte counts, as compared with follow-up counts, were decreased in the overall population (P < .0001); however, the percentage of CD4+ T cells remained unchanged during the course of pneumonia in each patient. These changes that were noted for the overall population were not significantly influenced by age, the presence (or not) of infection with human immunodeficiency virus (HIV), or etiologic microorganisms. Of the 68 HIV-seronegative patients, 12 had initial CD4+ T cell counts of < 200/mm3; multivariate analysis revealed that this finding was significantly associated with the presence of an underlying disease or tuberculosis and an age of > or = 60 years.

AIDS-Related Opportunistic Infections↗

AIDS-related conditions: study of a representative sample of 1203 patients deceased in 1992 in France.

BACKGROUND: Little representative information exists on the frequency of human immunodeficiency virus (HIV)-related diseases among the overall AIDS population. The objective of this research is to assess the nature, frequency and characteristics of these diseases among AIDS patients during their last year of life and to analyse these frequencies according to the mode of transmission and other socio-demographic and medical characteristics. METHODS: To obtain comprehensive data, we conducted an investigation based on retrospective collection of clinical information on a representative sample (1203 deaths) of all AIDS deaths that occurred in France during 1992. RESULTS: The frequency of the diseases was markedly higher than the one described in the AIDS surveillance registers and varied between homosexuals and intravenous drug users (IVDU). After controlling for other variables (age, CD4 counts, survival times) by means of logistic regression, homosexuality remained a significant explaining factor for Kaposi's sarcoma, cytomegalovirus infections, herpes simplex and cryptosporidiosis. In contrast, HIV encephalopathy, hepatitis, mental disorders, invasive candidiasis and cachexia were more frequent in male IVDU. Few differences were observed by sex. CONCLUSIONS: Several factors may explain the differences: variation in exposure to infectious agents, general health status, use of medical care and direct influence of the mode of HIV transmission. These data are of particular value for medical services in planning the magnitude of health care needs among the AIDS population overall, for clinicians and researchers for advancing the understanding of the natural history of AIDS and in the definition of prophylactic strategies against opportunistic infections.

AIDS Dementia Complex↗

A new model of experimental prosthetic joint infection due to methicillin-resistant Staphylococcus aureus: a microbiologic, histopathologic, and magnetic resonance imaging characterization.

Partial knee arthroplasty was done in rabbits with a silicone-elastomer implant. Immediately after closing the surgical wound, 5 x 10(6) cfu of methicillin-resistant Staphylococcus aureus was injected into the joint. Disease evolution was studied at different stages of infection up to 8 weeks. Prosthetic infection developed in all animals. Gross pathology and histopathologic changes were characteristic of joint and bone infection. Quantitative bacterial counts from infected bone confirmed disease chronicity. The mean number of colony-forming units per gram of bone +/- SD 1 week after infection was 4.84 +/- 0.24 log10 cfu/g and remained stable from week 1 to week 8. Magnetic resonance imaging showed evidence of prosthetic infection as of week 1, while only mild radiologic changes of bone were seen 2 weeks after infection. This model produces a prosthetic infection that is reproducible and close to that of human prosthetic infection.

Animals↗

Economic analysis of antibiotic regimens used in the treatment pharyngitis: a prospective comparison of azithromycin versus roxithromycin.

The economic impacts in terms of cost and effectiveness (speed of resolution of symptoms) of 3- and 5-day courses of azithromycin and a 10-day course of roxithromycin were compared in a randomized, open study in patients with symptoms suggestive of beta-haemolytic streptococcal pharyngitis. Direct medical costs and absence from work were recorded and symptom scores and compliance were used to assess the effectiveness of therapies. Although no differences between treatment groups in terms of overall clinical response rates were detected 2 and 4 weeks after the start of treatment, more rapid resolution of symptoms was achieved with 3- and 5-day courses of azithromycin than with a 10-day course of roxithromycin. There was also a significant reduction in the time absent from work in the azithromycin treatment groups. The total costs of care over the 4-week evaluation period were lower for the 3- and 5-day azithromycin courses (US$193.60 and US$195.30 respectively) than for roxithromycin (US$202.10). The major cost components were absence from work (58.6%), visits to the physician (15.3%) and utilization of antibiotics (14.9%). Compliance was significantly better (P < 0.01) in patients prescribed azithromycin for 3 and 5 days (58.0% and 42.9% respectively) than in those who received roxithromycin (20.3%) and a significantly longer symptom-free period (P < 0.01) was reported in azithromycin- compared with roxithromycin-treated patients. These findings support the hypothesis that a 3- or 5-day course of azithromycin is as effective as a 10 day course of roxithromycin in the treatment of patients with pharyngitis and is associated with lower costs. Furthermore, azithromycin is associated with faster resolution of symptoms and improved patient compliance.

Acute Disease↗

Excretion of ciprofloxacin into the large bowel of the rabbit.

The intestinal elimination of ciprofloxacin in the large bowel was studied in a rabbit model. Segments from the cecum, colon, and sigmoid colon along with their intact blood vessels were isolated and perfused, and their contents were collected over a 90-min period following the administration of a single parenteral dose of 27 mg of ciprofloxacin per kg of body weight. The elimination rates of ciprofloxacin were 0.126 +/- 0.084 micrograms.min-1.cm-2 in the cecum and 0.264 +/- 0.126, 0.11 +/- 0.07, and 0.21 +/- 0.141 micrograms.min-1.cm-2 in the proximal colon, distal colon, and sigmoid colon, respectively. The calculated fraction of ciprofloxacin eliminated in the large bowel was 3% of the parenteral dose administered. The elimination pattern of ciprofloxacin in the large bowel may explain the unusual activity of this fluoroquinolone in modifying the colonic flora.

Animals↗

Comparison of fluconazole and amphotericin B for treatment of experimental Candida albicans endocarditis in rabbits.

Amphotericin B (AmB) and fluconazole, administered intraperitoneally for 7 days, were compared in a rabbit model for Candida albicans endocarditis. When given early, AmB was more effective than fluconazole for reducing CFU counts in vegetations (P < 0.01) and kidneys. Forty-eight hours after the last dose, AmB was still detected in all vegetations whereas fluconazole was detected in only one case.

Amphotericin B↗

Efficacies of cefotaxime and ceftriaxone in a mouse model of pneumonia induced by two penicillin- and cephalosporin-resistant strains of Streptococcus pneumoniae.

We previously demonstrated the efficacy of ceftriaxone (CRO), at 50 mg/kg of body weight every 12 h, against a highly penicillin-resistant (MIC, 4 micrograms/ml) Streptococcus pneumoniae strain with low-level resistance to CRO (MIC, 0.5 microgram/ml) in a leukopenic-mouse pneumonia model (P. Moine, E. Vallée, E. Azoulay-Dupuis, P. Bourget, J.-P. Bédos, J. Bauchet, and J.-J. Pocidalo, Antimicrob. Agents Chemother. 38:1953-1958, 1994). In the present study, we assessed the activity of CRO versus those of cefotaxime (CTX) and amoxicillin (AMO) against two highly penicillin- and cephalosporin-resistant S. pneumoniae strains (P40422 and P40984) (MICs of 2 and 8 for penicillin, 2 and 4 for AMO, and 4 and 8 for CRO or CTX, respectively). Against both strains, a greater than an 80% cumulative survival rate was observed with CRO at a dose of 100 or 200 mg/kg every 12 h (dose/MIC ratio, 25). With CTX, a high dosage of 400 mg/kg (dose/MIC ratio, 100 or 50) administered every 8 h (TID) was needed to protect 66 and 75% of the animals, respectively, with no statistically significant differences versus CRO. Against the P40422 strain, CRO (100 mg/kg) produced the greatest bactericidal effect, from the 8th to the 24th hour after a single injection (1.8-log-unit reduction over 24 h), and the fastest bacterial pulmonary clearance during treatment; with CTX, only multiple injections at a high dosage, i.e., 400 mg/kg TID, demonstrated a significant bactericidal effect. AMO in a high dosage, 400 mg/kg (dose/MIC ratio, 200) TID, showed good activity only against the P40422 strain. Despite the identical MICs of CTX and CRO, the longer time (3.6 to 4.6 h) that serum CRO concentrations remained above the MICs for the pathogens at a dose of 100 mg/kg resulted in greater efficacy versus CTX against highly penicillin- and cephalosporin-resistant S. pneumoniae strains.

Amoxicillin↗

Resistance to amikacin and isepamicin in rabbits with experimental endocarditis of an aac(6')-Ib-bearing strain of Klebsiella pneumoniae susceptible in vitro.

The effect of production of the aminoglycoside 6'-N-acetyltransferase [AAC(6')-IB] in Klebsiella pneumoniae on the outcome of amikacin and isepamicin treatment of rabbits with experimental endocarditis was assessed. Isogenic high-level (Hi) and low-level (Lo) AAC(6')-Ib-producing transconjugants (T) were constructed from clinical isolates with plasmid-borne resistance determinants. The MICs of amikacin and isepamicin, their bactericidal effects, and AAC(6')-Ib production appeared to be well correlated among the clinical isolates and the transconjugants. The susceptibility data determined in vitro, with MICs (in micrograms per milliliter) of amikacin and isepamicin for LoT and HiT of 4 and 0.5 and 32 and 8, respectively, were, however, not predictive of the in vivo efficacies of the drugs. While amikacin and isepamicin caused reductions in bacterial densities (log10 CFU per gram of cardiac vegetation) of 5.1 and 4.8 of the fully susceptible recipient strain (MICs of amikacin and isepamicin, 0.5 and 0.25, respectively), the reductions in density of both LoT and HiT caused by the two drugs (2.7 and 2.4 and 2.9 and 2.2, respectively) were only marginally significant, if at all. There was no significant difference (P > 0.05) when the reductions in density of LoT and HiT by either drug were compared or when the efficacies of the two drugs in reducing the density of any strain [non-AAC(6')-producing, LoT, or HiT] were compared (P > 0.5). It is concluded that AAC(6')-Ib in K.pneumoniae, even when produced at a low level and not conferring resistance to amikacin and isepamicin in vitro, compromises the efficacies of both drugs in vivo and possibly does so beyond the experimental model studied here.

Acetyltransferases↗

Effects of nifedipine and diltiazem on pharmacokinetics of cefpodoxime following its oral administration.

We compared the effects of nifedipine and diltiazem on the uptake of cefpodoxime proxetil (CP). The study was aimed at establishing the impact of increased mesenteric blood flow due to calcium channel blockers on passive transport. Twelve volunteers were given CP (200 mg) orally in a crossover design. The absorption, disposition, and elimination parameters of cefpodoxime were compared among the following three treatment groups: CP alone, CP following oral administration of diltiazem (60 mg), or CP following oral administration of nifedipine (20 mg). No statistically significant difference in pharmacokinetic parameters was observed between the three treatment groups.

Administration, Oral↗