Cleocin
Compatibility and stability of cefazolin sodium, clindamycin phosphate, and gentamicin sulfate in two intravenous solutions.

Zbrozek AS, Marble DA, Bosso JA.

Hospital Pharmacy Management, University Hospital, University of Utah, Salt Lake City 84112.

We studied the compatibility and stability of clindamycin phosphate admixed with gentamicin sulfate and cefazolin sodium in small-volume diluents under specific storage conditions. In two replicate 100 ml dilutions of NaCl 0.9% injection and dextrose 5% (D5W) injection, clindamycin phosphate 900 mg was admixed with gentamicin sulfate 80 mg and cefazolin sodium 1 g. Drug concentrations were determined at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Clindamycin and cefazolin were assayed by high-performance liquid chromatography and gentamicin was assayed by fluorescence polarization immunoassay. Visual inspections and pH determinations of each solution were performed at each assay time. Test solutions were maintained at constant room temperature and fluorescent lighting. Concentrations of clindamycin and gentamicin remained greater than 90 percent of the original concentrations throughout the study. Cefazolin concentrations dropped below 90 percent in D5W injection at 4 hours after admixture and at 12 hours after admixture in NaCl 0.9% injection. Visual analyses and pH changes revealed no significant changes. The combination of clindamycin phosphate 900 mg, gentamicin sulfate 80 mg, and cefazolin sodium 1 g in D5W 100 ml was found to be compatible for up to 4 hours. The duration of compatibility for these three drugs in 100 ml of NaCl 0.9% was 12 hours.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3234252&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Effects of clindamycin and metronidazole on the intestinal colonization and translocation of enterococci in mice.

Wells CL, Jechorek RP, Maddaus MA, Simmons RL.

Department of Surgery, University of Minnesota, Minneapolis 55455, USA.

The intestinal colonization and translocation of enterococci was studied in mice treated intramuscularly with metronidazole or clindamycin, with or without oral streptomycin. Treatment with metronidazole resulted in selective elimination of strictly anaerobic cecal bacteria, with a 100-fold increase in the numbers of aerobic and facultative gram-negative bacilli and a 10,000-fold increase in the numbers of aerobic and facultative gram-positive species. Clindamycin had a similar effect on the cecal flora except that the numbers of aerobic and facultative gram-positive bacteria decreased at least 10-fold. The predominating gram-positive species in the cecal flora or metronidazole-treated mice was an enterococcus, but this organism could not be recovered from the ceca of clindamycin-treated mice. Translocating bacteria (primarily gram-negative enteric bacteria) were recovered from the mesenteric lymph nodes of the majority of mice given metronidazole or clindamycin. Gram-positive bacteria were not recovered from the mesenteric lymph nodes of 20 clindamycin-treated mice, whereas 26% of 19 metronidazole-treated mice had translocating enterococci. With addition of streptomycin to the metronidazole and clindamycin regimens, mice treated with metronidazole-streptomycin became colonized predominantly with an enterococcus, and this was the only translocating species recovered from 13% of 23 mice; however, enterococci could not be detected in the ceca of clindamycin-streptomycin-treated mice, and Bacillus spp. were recovered from the mesenteric lymph nodes of 8% of 24 mice, reflecting the composition of the cecal flora. The apparent elimination of enterococci from the ceca of clindamycin and clindamycin-streptomycin-treated mice was inconsistent with the observation that the average (n=6) peak levels of clindamycin in blood and ceca were 25 and 21 microgram/ml, respectively, whereas the in vitro MIC was 128 microgram/ml. However, this apparent in vivo activity of clindamycin against enterococci was not evident in mice given 10(9) oral enterococci; the concentrations of cecal enterococci in both clindamycin-streptomycin- and metronidazole-streptomycin-treated mice were 10(10) to 10(11) enterococci per g, with translocating enterococci recovered from approximately half of these antibiotic-treated mice. Thus antibiotic therapy with metronidazole, clindamycin, metronidazole-streptomycin, and clindamycin-streptomycin resulted in a wide variation in the cecal population levels and translocation frequencies of enterococci. This variation appeared to be related to the discrepancy between the in vivo and in vitro activities of clindamycin against enterococci.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3245692&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Comparative pharmacokinetics and serum inhibitory activity of clindamycin in different dosing regimens.

Flaherty JF, Rodondi LC, Guglielmo BJ, Fleishaker JC, Townsend RJ, Gambertoglio JG.

Division of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0622.

The comparative pharmacokinetics and serum inhibitory effects of clindamycin were evaluated in six healthy male subjects given multiple-dose infusions of the following regimens in a crossover fashion: 600 mg every 6 h, 900 mg every 8 h, and 1,200 mg every 12 h. Serial blood samples were obtained after the last dose in each regimen and analyzed for clindamycin by a sensitive and specific high-performance liquid chromatography assay technique. Clindamycin pharmacokinetics were estimated by using noncompartmental methods, and serum inhibitory titers were serially determined against Bacteroides fragilis ATCC 25285 and evaluated by using area under the serum inhibitory curve (AUIC). Maximum and minimum concentrations in plasma averaged 12.2 +/- 1.6 and 1.2 +/- 0.6, 16.3 +/- 4.0 and 0.9 +/- 0.5, and 16.8 +/- 2.5 and 0.4 +/- 0.2 micrograms/ml for the 600-, 900-, and 1,200-mg regimens, respectively. Clindamycin plasma clearance and elimination half-life averaged 23.3 +/- 4.0 liters/h and 1.9 +/- 0.4 h for the 600-mg regimen, 25.6 +/- 8.2 liters/h and 2.1 +/- 0.4 h for the 900-mg regimen, and 26.4 +/- 4.7 liters/h and 2.1 +/- 0.4 h for the 1,200-mg regimen. These results were not significantly different. Apparent volume of distribution increased significantly for the 1,200-mg regimen compared with the 600-mg regimen. Mean maximum reciprocal serum inhibitory titers were 96 +/- 35, 101 +/- 43, and 160 +/- 78 for the 600-, 900-, and 1,200-mg regimens, respectively. Minimum reciprocal serum inhibitory titers averaged 12 +/- 4, 6 +/- 3, and 5 +/- 2 for the low-, medium-, and high-dose regimens, respectively. Mean AUIC increased roughly in proportion to dose. Similar daily values for the area under the concentration-time curve and for AUIC for each of the regimens suggest similar daily drug exposure and serum inhibitory activity. A regimen of 1,200 mg every 12 h may represent an alternative dosing strategy for clindamycin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3245695&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Activity of clindamycin with primaquine against Pneumocystis carinii in vitro and in vivo.

Queener SF, Bartlett MS, Richardson JD, Durkin MM, Jay MA, Smith JW.

Department of Pathology, Indiana University School of Medicine, Indianapolis 46223.

The combination of primaquine with clindamycin is effective in both in vitro and in vivo models of Pneumocystis infection. Primaquine alone at concentrations from 10 to 300 micrograms/ml reduced the numbers of organisms in cultures to less than 7% of control. Significant inhibition was observed down to 0.1 microgram/ml. Clindamycin at 5 micrograms/ml was ineffective alone. Combinations of clindamycin and primaquine in culture at various concentrations were effective, but there was no evidence of true synergy. In rats with established Pneumocystis pneumonia, clindamycin alone at 5 or 225 mg/kg was ineffective. Primaquine alone at 0.5 or 2 mg/kg did not significantly affect the numbers of organisms remaining. The combination of 0.5 mg of primaquine per kg and 225 mg of clindamycin per kg was effective for therapy, lowering the numbers of organisms in the lungs by about 90%. The combination of 2 mg of primaquine per kg and 225 mg of clindamycin per kg was more effective, lowering the numbers of organisms by almost 98%. In the in vivo prophylaxis model, primaquine at 0.1 or 0.2 mg/kg did not prevent the development of Pneumocystis pneumonia in immune-suppressed rats. Clindamycin at 50 mg/kg had a modest effect alone, but at 5 mg/kg all animals became heavily infected. At 0.5 mg/kg, primaquine alone reduced the severity of infection, but seven of eight rats were still infected. In contrast, the combination of 5 mg of clindamycin per kg and 0.5 mg of primaquine per kg prevented infection in 8 of 10 rats; 2 rats had minimal infection. These studies suggest that the combination of clindamycin and primaquine should be tested in therapy or prophylaxis of Pneumocystis infections in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3261959&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Clindamycin-induced alteration of ganglionic function. I. Direct effects on ganglion cell properties.

Konopka LM, Parsons RL.

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

The influence of the lincosamide antibiotic, clindamycin, on the properties of bullfrog sympathetic ganglion B cells has been determined in vitro using conventional voltage recording methods or single microelectrode voltage-clamp recording techniques. Individual neurons were depolarized with both bath application or local perfusion of clindamycin. The amplitude of the depolarization was not altered by pretreatment with 50 microM (+)-tubocurarine, 10-microM atropine, or 1.5 microM tetrodotoxin (TTX), indicating that the clindamycin-induced depolarization does not result from either the activation of (1) nicotinic receptors, (2) muscarinic receptors, or (3) voltage-gated sodium channels. Clindamycin partially inhibited IM, an action which accounts for part of the clindamycin-induced depolarization. The duration of the hyperpolarizing afterpotential (HAP) following the action potential was decreased in the presence of clindamycin. Clindamycin decreased the amplitude and maximum rate of rise (MRR) of TTX-insensitive action potentials. As calcium influx is thought to contribute to the depolarizing phase of the TTX-insensitive spikes, we suggest that the decrease in HAP duration by clindamycin results from a decrease in the somal calcium current. Further, it is suggested that a decrease in IM and HAP duration may be responsible for the increased excitability exhibited during exposure to clindamycin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3264742&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
The Eagle effect revisited: efficacy of clindamycin, erythromycin, and penicillin in the treatment of streptococcal myositis.

Stevens DL, Gibbons AE, Bergstrom R, Winn V.

Department of Medicine, Veterans Administration Medical Center, Boise, Idaho 83702.

We investigated the relative efficacies of penicillin, clindamycin, and erythromycin in a mouse model of myositis due to Streptococcus pyogenes. Penicillin was ineffective unless given at the time of bacterial injection, and treatment delays of 2 h reduced its efficacy such that survival was no better than that of untreated control animals (P less than .05). Survival of erythromycin-treated mice was greater than that of both penicillin-treated mice and untreated controls, but only if treatment was begun within 2 h. Mice receiving clindamycin, however, had survival rates of 100%, 100%, 80%, and 70% even if treatment was delayed 0, 2, 6, and 16.5 h, respectively. Thus, clindamycin demonstrated superior efficacy to penicillin among all the various treatment groups (P less than .05). Our results corroborate the failure of penicillin in this model of streptococcal infection and suggest that, unlike penicillin, the efficacy of clindamycin is not adversely altered by the "Eagle effect."

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3292661&dopt=Abstract clindamycin antibiotic Cleocin-T