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Macrolides are widely used in the treatment of respiratory infections. Here, the authors compared the activity of different 14-membered macrolides: erythromycin (Ery), roxithromycin (Rox), clarithromycin (Cla) and its 14-hydroxy metabolite 14-OH clarithromycin (14-OH) against 30 strains of Streptococcus pneumoniae isolated at the Dupuytren hospital (Limoges, France) from upper respiratory tract sputum, ophthalmic sputum, blood samples and CSF. Twenty strains were susceptible to macrolides and 10 were resistant. Three strains from the susceptible and 7 from the resistant were resistant to penicillin. Furthermore, for all the macrolides except Rox and 14-OH, susceptibility tests were performed by the disk diffusion method on Mueller-Hinton agar. MICs50 of Cla and Ery were 0.06 mg/l. They were two-fold increased for 14-OH (0.125 mg/l) and four-fold increased for Rox (0.25 mg/l). We noted that for 3 resistant strains, MICs of Cla were four-fold decreased than MICs of Ery. Ery, Cla and 14-OH had bactericidal activity against pneumococcus strains susceptible to these antibiotics at 4 and 8 times the MIC after 6 or 18 h. The difference between MIC and MBC was small (1 or 2 two-fold dilutions) for Ery, Rox and Cla. For 14-OH, this difference was within 2 to 4 two-fold dilutions. The bactericidal activity is similar to that of amoxicillin and cefotaxim. A microdilution chequeboard technique was used against 3 strains and the FIC index did not show synergistic effect of combining Cla and 14-OH. The activity of Cla and 14-OH against 5 strains was not modified in the presence of 50% fresh pooled human serum inactivated at 56 degrees C or not.
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The type of oral dosage forms of roxithromycin altered its pharmacokinetics. Whether or not this affects the in vivo antibacterial efficacy requires further study.
The removal of 11 antibiotics of 6 classes, that is, two beta-lactams (ampicillin and cefalexin), two sulfonamides (sulfamethoxazole and sulfadiazine), three fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin), one tetracyclines (tetracycline), two macorlides (roxithromycin and anhydro-erythromycin), and one others (trimethoprim), in activated sludge process was investigated using two series of batch reactors treating freshwater and saline sewage respectively. At environmental relevant concentrations tested in this study, biodegradation and adsorption were the major removal routes for the target antibiotics, where volatilization and hydrolysis were neglectable. Among the 11 target antibiotics, cefalexin and the two sulfonamides were predominantly removed by biodegradation in both freshwater and saline sewage systems. Ampicillin, norfloxacin, ciprofloxacin, ofloxacin, tetracycline, roxithromycin, and trimethoprim were mainly removed by adsorption. Divalent cations (Ca(2+) and Mg(2+)) in saline sewage significantly decreased the adsorption of the three fluoroquinolones onto activated sludge. These three fluoroquinolones also exhibited certain biodegradability in the saline activated sludge reactor. Erythromycin-H(2)O was persistent in both saline and freshwater systems under the experimental conditions and could not be removed at all. Kinetics study showed that biodegradation of cefalexin, the two sulfonamides and the three fluoroquinolones followed first-order model well (R(2): 0.921-0.997) with the rate constants ranging from 5.2 x 10(-3) to 3.6 x 10(-1) h(-1).
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Overall, macrolide use was associated with a statistically significant mortality reduction compared with nonmacrolide use (OR: 0.65, 95% CI: 0.46-0.92). There was no difference in the risk of cardiac death between macrolide and nonmacrolide regimes (OR: 1.43, 95% CI: 0.86-2.40). In subgroup analyses, macrolide use was found to be associated with the decreased risk of mortality in a population of older individuals (age>48 years, OR: 0.69; 95% CI: 0.66-0.72). While in a general population of young and middle-aged adults, the use of macrolide-based regimens could not decrease the risk of death from any cause (age<48 years, OR: 0.42; 95% CI: 0.02-11.01). As for cardiac death, macrolide use was found to be associated with increased risk of cardiac death in a population of older individuals (age>48 years, OR: 1.99; 95% CI: 1.53-2.59).
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Emerging evidence suggests an association between some asthma and pulmonary infection by the atypical organisms Chlamydia pneumoniae and Mycoplasma pneumoniae, but a causal role for infection remains unproven and controversial. Most acute exacerbations of asthma are triggered by acute infections that are due to viral respiratory pathogens, not to bacteria or atypical organisms. Administration of antibiotics for acute exacerbations of asthma has been shown to be ineffective. Most evidence linking atypical infections to asthma is consistent with a promoting role for chronic infection in producing persistent asthma symptoms. Preliminary studies suggest that prolonged (>/=6 weeks) administration of doxycycline or macrolides may eradicate C. pneumoniae from respiratory secretions and improve long term, not acute, asthma symptoms. Randomised, controlled trials are currently under way to investigate the effectiveness of these prolonged courses of macrolides and azalides (roxithromycin, clarithromycin and azithromycin) in adults with stable persistent asthma. Traditional courses (7 to 10 days) of any antibiotic are incapable of eradicating chronic C. pneumoniae or M. pneumoniae infection; furthermore, beta-lactam and sulphonamide-based antibiotics that are commonly prescribed in acute respiratory syndromes are ineffective against these atypical organisms. Unless the goal is to treat documented sinusitis associated with asthma, it is inappropriate to prescribe traditional courses of any antibiotic for acute asthma exacerbations; whether longer courses of antibiotics should be prescribed to eradicate chronic atypical infections and decrease persistent asthma severity remains to be established.
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The effects of a new semisynthetic macrolide, roxithromycin, on drug metabolizing enzymes of rat liver were compared with two erythromycins, the base (EB) and the estolate (EE), after 7 days' treatment with high oral doses (400 and 800 mg/kg daily). Dose-related higher concentrations of roxithromycin were reached in serum and liver than after EB or EE. The two reference erythromycins induced the synthesis of microsomal enzymes and formed inactive cytochrome P-450-metabolite complexes. N-Demethylation of erythromycin itself and aminopyrine was increased by the treatment. Liver microsomal enzyme activities were not induced and the inactive cytochrome P-450-metabolite complex was not formed after 400 mg/kg of roxithromycin and only to a very limited extent after 800 mg/kg (10% vs. 50% after EE). At the higher dose microsomal activities were not changed by roxithromycin and only aminopyrine N-demethylation was reduced.
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We included 196 adults who had presented to a general practitioner with lower respiratory tract infection (LRTI) and, in the physician's opinion, needed antibiotic treatment.