Drugs online research references
J Antimicrob Chemother. 2003 May;51(5):1167-73. Epub 2003 Apr 14.
Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus.
Seral C, Carryn S, Tulkens PM, Van Bambeke F.
Unite de Pharmacologie Cellulaire et Moleculaire, Universite Catholique de Louvain, UCL 73.70 Avenue E. Mounier 73, B-1200 Brussels, Belgium.
Antibiotic efflux pumps expressed in eukaryotic cells can decrease the intracellular accumulation of the corresponding drugs and therefore impair their activity against intracellular bacteria. We have investigated whether verapamil (an inhibitor of P-glycoprotein) and gemfibrozil (an inhibitor of multidrug resistance proteins (MRP) and other organic anion transporters), can modulate the intracellular activity of azithromycin and ciprofloxacin against Listeria monocytogenes and Staphylococcus aureus in J774 macrophages. In parallel, we have measured the cell accumulation and subcellular distribution of both drugs. Antibiotics were used at equipotent extracellular concentrations (from 0.5 x to 10 x MIC) to allow for pharmacological comparisons. Azithromycin was bacteriostatic against L. monocytogenes and slightly bactericidal against S. aureus. Verapamil did not improve the maximal activity of azithromycin but allowed it to reach a similar effect at extracellular concentrations about seven-fold lower in both models. Azithromycin was predominantly localized in cell granules (66%), the remainder being in the cytosol and in the 'nuclei/unbroken cells' fraction. Verapamil increased the cellular accumulation of azithromycin by almost 2.4-fold without modifying its subcellular distribution. Ciprofloxacin displayed a strong concentration-dependent bactericidal activity in both models. Gemfibrozil increased ciprofloxacin activity almost 2.5-fold against L. monocytogenes, but not against S. aureus. Ciprofloxacin was predominantly (65%) distributed in the cytosol. Gemfibrozil increased ciprofloxacin total accumulation by approximately 2.4-fold, but the excess was only found in the cytosol. Inhibition of efflux pumps may be a useful strategy to improve antibiotic efficacy against intracellular bacteria when increased accumulation can be obtained in the compartment where bacteria sojourn.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12697643&dopt=Abstract
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Emerg Infect Dis. 2003 Apr;9(4):480-2.
Scrub typhus in the Torres Strait islands of north Queensland, Australia.
Faa AG, McBride WJ, Garstone G, Thompson RE, Holt P.
Thursday Island Hospital, Queensland, Australia.
Scrub typhus, caused by Orientia tsutsugamushi, occurs throughout Southeast Asia. We descript ten cases that occurred in the Torres Strait islands of northern Australia during 2000 and 2001. Preceding heavy rain may have contributed to the outbreak. The successful use of azithromycin in two pediatric patients is also reported.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12702230&dopt=Abstract
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mf.uni-lj.si
OBJECTIVES: Prolongation of the corrected Q-T (Q-Tc) interval is associated with a risk of severe and even life-threatening arrythmias. It may occur as an adverse effect of various pharmacological agents including macrolides. We opted to study the influence of the azalide antibiotic azithromycin on the duration of Q-Tc interval as data on this subject are limited. METHODS: A prospective study was performed on 47 patients, 31 females and 16 males, aged 19-77 (median 52) years, treated with azithromycin (total dosage 3 g, divided over 5 days) for typical solitary erythema migrans. The patients were previously healthy and were not receiving any other medication. In all of them ECGs were performed before as well as 7 and 14 days after initiation of the azithromycin therapy. Thus, a total of 141 ECG tracings were analyzed. Q-T intervals were measured manually in a blinded manner and corrected for heart rate according to Bazzet's formula: Q-Tc = measured Q-T (ms)/square root of R-R (s). RESULTS: Comparison of the Q-Tc intervals before, 7 days, and 14 days after the initiation of azithromycin treatment revealed a mild, but not significant prolongation (median values 406, 412.5 and 419 ms with ranges of 339-488, 352-510, and 346-505 ms, respectively). Q-Tc intervals exceeding the upper normal value of 440 ms were found in the same proportion of patients prior to as after institution of treatment. None of the ECG tracings showed significant arrhythmias. CONCLUSION: In previously healthy persons, a modest statistically insignificant prolongation of the Q-Tc interval without clinical consequences was observed after completion of a course of 3 g of azithromycin administered over a period of 5 days for solitary erythema migrans.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12708094&dopt=Abstract
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