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Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serum levels of the three macrolides--roxithromycin, clarithromycin and azithromycin--vary considerably. The prediction of the antibacterial effect against extracellular pathogens is based on circulating concentrations of free drug, peak and trough levels, the rate of killing, and the presence of a post-antibiotic effect. Intracellular activity depends on the distribution of the antibiotic and the localization of the bacteria, and is variable. Roxithromycin uptake is greater than that of erythromycin. The intracellular half-life may be long for some compounds (azithromycin > roxithromycin). The intracellular distribution is bimodal, both in the lysosomes and the cytoplasm, but the mechanisms of uptake have not yet been established. At low pH, accumulation is low and macrolides are less active in an acidic medium. Intracellular concentrations cannot readily be predicted on the basis of extracellular levels. Different models have shown that the greater the intracellular concentration, the better the clinical effect. In addition, the transport of macrolides by cells into the infected focus may play an important role in the therapeutic outcome. These factors influence the clinical indications for macrolides, their dosing regimens and breakpoints. In future, macrolides will be developed that are more selective for intracellular infections, while others, which will achieve significant serum levels, will be useful for a broader range of diseases. However, new compounds should be evaluated in different models of infection before clinical studies are instituted. The analysis of failures remains the most important approach in defining concentration/effect relationships.
Infection 1995
PMID:Clinical relevance of intracellular and extracellular concentrations of macrolides. 778 9

Two hundred and forty-two patients over 16 years of age with community-acquired lower respiratory tract infection (LRTI), matched for age and sex, were randomised to receive either roxithromycin 150 mg b.i.d. or amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for 7 days, with a further 7 days if insufficient response was seen. Clinical efficacy at 7 days was 69% for roxithromycin and 56% for amoxycillin/clavulanic acid (p = 0.05) and at study end it was 91% for both antibiotics. There were fewer second treatment courses in the roxithromycin group (26% vs. 38%, p = 0.04) and a shorter treatment duration (8.29 days vs. 9.34 days, p > 0.05). Twelve patients (9.8%) treated with roxithromycin and 19 (17.1%) treated with amoxycillin/clavulanic acid had adverse effects possibly, or probably, related to the antibiotic. Roxithromycin appears to be a more appropriate choice than amoxycillin/clavulanic acid for the treatment of LRTI in the community given its more appropriate in vitro spectrum, efficacy against most common and atypical pathogens, greater cost-effectiveness, more convenient dosage regimen (b.i.d.), and superior tolerability profile.
Infection 1995
PMID:Roxithromycin 150 mg b.i.d. versus amoxycillin 500 mg/clavulanic acid 125 mg t.i.d. for the treatment of lower respiratory tract infections in general practice. 778 10

The prevention of cerebral toxoplasmosis and of Pneumocystis carinii pneumonia is an essential objective in the management of patients infected with HIV. Given that roxithromycin is active in vitro against Toxoplasma gondii and that in 1989 Dolermann reported the effective treatment of P. carinii respiratory infections with erythromycin, a randomized pilot study was undertaken in 52 patients infected with HIV. Patients were treated with either: a monthly dose of pentamidine aerosol (300 mg); roxithromycin once a week (300 mg t.i.d.); or a combination of pentamidine aerosol and roxithromycin. Intention to treat analysis was applied to these 52 patients, all of whom received at least one treatment dose. Five out of 18 patients treated with pentamidine aerosol, 1/17 patients treated with pentamidine aerosol + roxithromycin and none of the 17 patients treated with roxithromycin developed cerebral toxoplasmosis (p = 0.038). P. carinii pneumonia was diagnosed in one patient in the pentamidine aerosol-treated group, in one patient treated with roxithromycin and in none of the patients treated with pentamidine aerosol + roxithromycin (non-significant difference). Four cases of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare infection were seen in the pentamidine aerosol-treated group (p = 0.028) and none in the roxithromycin groups. Adverse events leading to the discontinuation of treatment occurred in 5/34 (14.7%) patients treated with roxithromycin. Nausea, abdominal pain and raised transaminases occurred in four patients and a skin allergy in the final patient. Roxithromycin appears to be effective in the prevention of pulmonary pneumocystis infection and of cerebral toxoplasmosis in HIV-infected patients. However, these results require confirmation in a larger study.
Infection 1995
PMID:Prevention of Pneumocystis carinii pneumonia and of cerebral toxoplasmosis by roxithromycin in HIV-infected patients. 778 14

When macrolide antibiotics are administered according to the standard therapeutic regimens, the highest plasma concentrations of total drug, both during the first dosage interval and at steady state, are obtained with roxithromycin, followed by clarithromycin and azithromycin. The corresponding free plasma concentrations, calculated from published data on plasma protein binding for the three macrolides, are of the same order of magnitude and the highest values are again those of roxithromycin. With the use of improved analytical methodology, a stable and prolonged total elimination half-life of roxithromycin of about 19 h was demonstrated at steady state in healthy adults with a 300 mg once daily dosage regimen. Intra-group subject variations (adults, children, the elderly etc.) were smaller than anticipated. Roxithromycin is found in high and similar concentrations both in plasma and tissue, demonstrating a balanced pharmacokinetic behaviour.
Infection 1995
PMID:Pharmacokinetics of macrolides. Comparison of plasma, tissue and free concentrations with special reference to roxithromycin. 778 17

Prophylactic efficacy of antimicrobial agents against pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.
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PMID:Experimental evaluation of combined prophylaxis against murine pneumocystosis and toxoplasmosis. 807 24

Patients with erythema migrans can fail to respond to antibiotic therapy. Persistent or recurrent erythema migrans, major sequelae such as meningitis and arthritis, survival of Borrelia burgdorferi and significant and persistent increase of antibody titres against B. burgdorferi after antibiotic therapy are strong indications of a treatment failure. Most, if not all, antibiotics used so far have been associated with a treatment failure in patients with erythema migrans. Roxithromycin and erythromycin are definitely or probably ineffective. However, doxycycline, amoxicillin, cefuroxime, ceftriaxone, azithromycin and high-dose penicillin V perform comparably well.
Infection
PMID:Treatment failure in erythema migrans--a review. 885 75