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med.toho-u.ac.jp
Recently we have reported that sub-minimum inhibitory concentrations (MICs) of macrolide antibiotics, such as erythromycin, clarithromycin, and azithromycin, induce loss of viability of Pseudomonas aeruginosa with longer incubation periods. In the present study we examined the effects of sub-MICs of macrolide antibiotics on protein synthesis and the expression of heat shock proteins (Gro-EL) in P. aeruginosa and the association of these factors with the viability of P. aeruginosa. In seven strains of P. aeruginosa clinical isolates, inhibition of protein synthesis was generally observed in bacteria grown on agar with sub-MIC azithromycin (8 microg/ml) at 24 h, and this was followed by loss of viability after an additional 24-h incubation. The inhibition of protein synthesis was shown in bacteria treated with sub-MICs of erythromycin and clarithromycin, but not with sub-MICs of other antibiotics examined (josamycin, tobramycin, ofloxacin, clindamycin, and ceftazidime) even at relatively high sub-MICs. In the heat shock condition (45 degrees C), strong expression of the heat shock protein Gro-EL was induced in bacteria grown on antibiotic-free medium, whereas there was a delay of such a response in bacteria exposed to 4 microg/ml of azithromycin. Reflecting these results, an abrupt reduction of viability in azithromycin-treated bacteria was observed within 3 h in the heat shock condition. Western blot analysis, using specific antibody for Gro-EL, demonstrated that erythromycin, clarithromycin, and azithromycin, at concentrations of 0.5-2 microg/ml, inhibited the expression of lower-molecular weight Gro-EL bands in the constitutive state. These results indicated that macrolides, at concentrations far below the MICs, suppressed protein synthesis in P. aeruginosa, an effect which may be associated with the inhibition of P. aeruginosa virulence and its loss of viability with longer incubation. Moreover, it is likely that the macrolides may sensitize bacteria to stresses, as these antibiotics induced alterations in a major stress protein, Gro-EL, in constitutive and inducible states.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11810524&dopt=Abstract
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med.va.gov
This investigation assessed the impact of initial empirical antimicrobial therapy on the outcome of therapy for community acquired pneumonia (CAP) patients and on patients' length of stay (LOS) in the hospital. Hospital records for 165 patients with pneumonia admitted to the Edward Hines, Jr. VA Hospital between 1 October 1997, and 31 March 2000, were reviewed. Criteria for CAP were met for 92 of 165 patients. Comparisons were made between patients treated with azithromycin and with other parenteral antibiotics (the reference group). No statistical differences were observed between the treatment groups for the risk factors. The azithromycin group patients were slightly older with a mean age of 69 years versus 66 years (P=0.23). Patients treated with parenteral azithromycin had on average, a shorter length of hospitalization namely 4.6 days compared with 9.7 days for patients treated with the other antibiotics (log-rank test, P=0.0001). In order to make the two groups of patients more alike we considered patients' data set without intensive care unit (ICU) admissions. The conclusion was the same namely azithromycin monotherapy was associated with a decreased duration of hospital stay.
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J Antimicrob Chemother. 2002 Feb;49(2):407-9.
Endothelial cell compatibility of azithromycin and erythromycin.
Vorbach H, Armbruster C, Robibaro B, Griesmacher A, El-Menyawi I, Daxecker H, Raab M, Muller MM.
Department of Internal Medicine II, Pulmonary Centre, Vienna, Austria.
Phlebitis is a severe local adverse event related to the use of parenteral macrolides. In order to evaluate the effect of azithromycin and erythromycin on human venous endothelial cells, we set up an in vitro model. The intracellular levels of purine nucleotides, as adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP) and guanosine 5'-triphosphate (GTP), were measured by means of high-performance liquid chromatography. Incubation of cells with 2 mg/mL azithromycin and erythromycin resulted in a rapid decline of intracellular ATP from 12.5 +/- 0.9 nmol/million cells to 4.1 +/- 0.3 and 2.6 +/- 0.4 nmol/million cells, respectively, after 60 min. In addition, ADP was extensively depleted from 2.1 +/- 0.17 nmol/million cells to 0.8 +/- 0.09 and 0.8 +/- 0.13 nmol/million cells after 60 min. After exposure of 0.5 mg/mL azithromycin and erythromycin, no significant decline of intracellular high-energy phosphate levels occurred after 20 and 60 min. Based on these results, solutions of azithromycin and erythromycin may not be well tolerated and may cause local adverse reactions even if diluted according to the manufacturer's recommendation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11815590&dopt=Abstract
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