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In vitro synergy of clindamycin and aminoglycosides against Chlamydia trachomatis.

Pearlman MD, Faro S, Riddle GD, Tortolero G.

Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030.

The importance of Chlamydia trachomatis as an etiologic agent in the development of pelvic inflammatory disease (PID) is well documented. Although there are numerous antimicrobial agents that are effective against C. trachomatis, one of the most frequent combinations that is used to treat PID is clindamycin and gentamicin. The efficacy of clindamycin as the sole treatment for chlamydial infections has been questioned. In fact, the Centers for Disease Control (Atlanta, Ga.) has recommended the use of doxycycline following clindamycin and gentamicin treatment of PID confirmed or suspected to be caused by C. trachomatis. This study was designed to determine whether there is any synergistic in vitro activity between clindamycin and gentamicin or tobramycin on inhibition of C. trachomatis replication. In this experiment, the MIC of clindamycin decreased two- to threefold when an aminoglycoside was added. This occurred even though aminoglycosides by themselves had essentially no effect against C. trachomatis. The mechanism of this interaction is uncertain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2386371&dopt=Abstract clindamycin antibiotic Cleocin-T



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[Effect of treatment with clindamycin, erythromycin, rifamycin or gentamicin on the ingestion capacity of peritoneal macrophages in mice]

[Article in French]

Amurrio C, Lewden S, Nicolas R, Gonzalez P, Canavate ML, Cisterna R.

Departement de Microbiologie et Immunologie, Faculte de Medecine, Universite du Pays Basque, Lejona, Espagne.

The effect of treatment with clindamycin, erythromycin, rifamycin and gentamicin on the ingestion capacity of the mouse peritoneal macrophage was studied. Female six-eight week old OF1 mice were treated with minimum and maximum doses clinically used for the different antibiotics (15 and 40 mg/kg/day of clindamycin, 15 and 57.5 mg/kg/day of erythromycin, 10 and 30 mg/kg/day of rifamycin, 3 and 6 mg/kg/day of gentamicin). Two treatment periods of 72 hours and one week were assayed for each antibiotic-dose combination. Antibiotic was administered twice daily, every twelve hours. Twelve hours after the last dose was given, macrophages were obtained through peritoneal lavage and a kinetic study of Candida albicans blastospore ingestion was made. One week treatment with 15 mg/kg/day and 72 hours treatment with 57.5 mg/kg/day of erythromycin produced a significant ingestion enhancement whereas one week treatment with 57.5 mg/kg/day of erythromycin and all treatments with gentamicin gave rise to an ingestion depression. 72 hours treatment with 15 and 40 mg/kg/day and one week treatment with 15 mg/kg/day of clindamycin, 15 mg/kg/day of erythromycin and 10 and 30 mg/kg/day of rifamycin did not modify macrophage ingestion capacity. One week treatment with 40 mg/kg/day of clindamycin and 10 and 30 mg/kg/day of rifamycin gave rise to an acceleration of the ingestion process.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2407991&dopt=Abstract clindamycin antibiotic Cleocin-T



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Clindamycin-induced alteration of ganglionic function. II. Effect of nicotinic receptor-channel function.

Konopka LM, Neel DS, Parsons RL.

Department of Anatomy and Neurobiology, College of Medicine, University of Vermont, Burlington 05405.

The postsynaptic effects of clindamycin have been analyzed in bullfrog sympathetic ganglion B cells using single electrode current and voltage clamp recordings and two electrode voltage clamp measurements. Clindamycin added to the bathing solution in the concentration range, 2.5 x 10(-4) to 5 x 10(-4) M, inhibited fast ganglionic transmission. In addition, local application of clindamycin decreased depolarizations produced by direct application of acetylcholine and decreased the amplitude of miniature excitatory postsynaptic potentials (MEPSPs) evoked by tetanic stimulation of the preganglionic trunk. In contrast, clindamycin did not change the amplitude or time course of the slow EPSP elicited by preganglionic stimulation (30 Hz for 10 s) or muscarinic depolarizations produced by local acetylcholine application to preparations pretreated with 25-50 microM (+)-tubocurarine. In voltage-clamped ganglion cells, excitatory postsynaptic current (EPSC) amplitude initially was increased and then decreased with increasing concentrations of clindamycin (0.5 x 10(-5) to 2.5 x 10(-4) M). The EPSC time course in control cells was exponential. After exposure to clindamycin, the EPSC decay was composed of two exponential components. The time constant of the fast component decreased and the time constant of the slow component increased with increasing concentrations of clindamycin. The two time constants of EPSCs obtained in clindamycin were independent of membrane voltage between -50 and -100 mV. We concluded that the block of fast ganglionic transmission is primarily due to a postsynaptic site of action, at least part of which is due to a concentration-dependent, but voltage-independent blockade of open nicotinic receptor channel complexes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2463047&dopt=Abstract clindamycin antibiotic Cleocin-T



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The role of glycocalyx in surface phagocytosis of Bacteroides spp., in the presence and absence of clindamycin.

Veringa EM, Ferguson DA Jr, Lambe DW Jr, Verhoef J.

Department of Microbiology, College of Medicine, East Tennessee State University, Johnson City 37614-0002.

The influence of isolated glycocalyx from Bacteroides thetaiotaomicron and B. fragilis on surface phagocytosis of clindamycin-treated and -untreated homologous and heterologous species was studied. When homologous or heterologous isolated glycocalyx was added to clindamycin-treated B. thetaiotaomicron or B. fragilis before incubation with PMNL, phagocytosis was reduced to levels observed in the untreated control bacteria, but addition of glycocalyx to untreated control strains showed no reduction of phagocytosis. When isolated bacteroides-glycocalyx was added to Staphylococcus aureus or S. epidermidis, phagocytosis of both clindamycin-treated and -untreated bacteria was significantly reduced. The isolated glycocalyx preparations were analysed by thin layer and gas-liquid chromatography; these preparations were free of lipopolysaccharides. The isolated glycocalyx did not affect PMNL viability. Our findings suggest that the glycocalyx is an important virulence factor because it impairs phagocytosis of Bacteroides spp. by PMNL. Clindamycin may enhance opsonophagocytosis of bacteroides by altering the glycocalyx.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2474527&dopt=Abstract clindamycin antibiotic Cleocin-T



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Selection of constitutively resistant mutants of inducible clindamycin-resistant Bacteroides vulgatus.

Reig M, Baquero F.

Servicio de Microbiologia, Hospital Ramon y Cajal, Instituto Nacional de la Salud, Madrid, Spain.

The rate of spontaneous mutation to constitutive clindamycin resistance and the kinetics of selection of such mutants in preinduced and non-preinduced cells was evaluated in the Bacteroides vulgatus strain RYC18F6 (original MIC less than or equal to 0.25 micrograms/ml), which shows inducible resistance to clindamycin and erythromycin. Mutants demonstrating a high level of constitutive resistance to clindamycin (64 micrograms/ml) occurred at a frequency of 10(-7). Culture in broth containing either subinhibitory or inhibitory levels of clindamycin resulted in induction of clindamycin resistance. This permitted survival of a part of the population that seemed to facilitate the further growth of constitutively resistant mutants (up to a frequency of 10(-1)). At both low and high clindamycin concentrations mutants appeared to be selected over merely induced cells. Preincubation of cultures with erythromycin gave rise to an apparently higher level of induction. Under these circumstances, the selection of constitutively resistant mutants was less effective (10(-4). The use of erythromycin or clindamycin against populations of Bacteroides spp. exhibiting inducible resistance may contribute to selection of mutants showing constitutive clindamycin resistance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2506038&dopt=Abstract clindamycin antibiotic Cleocin-T



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Comparative evaluation of cefazolin and clindamycin in the treatment of experimental Staphylococcus aureus osteomyelitis in rabbits.

Mader JT, Adams K, Morrison L.

Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77550-2772.

A rabbit model for Staphylococcus aureus osteomyelitis was used to compare treatment with clindamycin and cefazolin. Cefazolin (5 mg/kg), cefazolin (15 mg/kg), and clindamycin (70 mg/kg) were injected subcutaneously every 6 h for 28 days. After treatment, S. aureus was found in bone cultures from 22 of 23 control rabbits, 12 of 22 rabbits treated with cefazolin (5 mg/kg), 12 of 23 rabbits treated with cefazolin (15 mg/kg), and 2 of 20 rabbits treated with clindamycin. Drug concentrations in serum, uninfected bone, and infected bone were measured 30 min after cefazolin or clindamycin was injected into a group of rabbits which had been infected for 3 to 4 weeks. Clindamycin gave the highest concentration in infected and uninfected bone. The results of the study showed that clindamycin was superior to cefazolin in the eradication of S. aureus from infected bone in an experimental model.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2589843&dopt=Abstract clindamycin antibiotic Cleocin-T









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