Cleocin
Decreased hepatic clearance of clindamycin in critically ill patients with sepsis.

Mann HJ, Townsend RJ, Fuhs DW, Cerra FB.

College of Pharmacy, University of Minnesota, Minneapolis 55455.

Clindamycin pharmacokinetics was compared in critically ill patients with sepsis and healthy volunteers, and the relationship between pharmacokinetic values and physiological measurements obtained from the critically ill patients was characterized. Pharmacokinetic evaluations were performed on 10 patients with sepsis who were receiving clindamycin phosphate 900 mg i.v. every eight hours and on 6 previously studied healthy men receiving the same dosage regimen. Physiological variables measured included age, weight, cardiac index, systemic vascular resistance, central venous pressure, liver-function tests, alpha 1-acid glycoprotein concentration, and APACHE II score. Clindamycin was administered to the critically ill patients via a central venous catheter over 30 minutes; the healthy volunteers received their infusions via a peripheral venous catheter over 30 minutes. Blood samples were obtained at five minutes before and at various intervals after drug administration. Serum clindamycin concentrations were determined by a gas-liquid chromatographic method. Serum concentration data were analyzed using noncompartmental methods based on statistical moment theory, and the a priori level of significance was 0.05. The critically ill patients had significantly increased values for area under the curve (AUC), area under the moment curve (AUMC), mean residence time (MRT), and average concentration at steady state (Css), while total body clearance (TBC) was less than half that in the healthy volunteers. TBC in three of the critically ill patients was not different from that in the healthy volunteers. The apparent volume of distribution at steady state (Vss) was not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3665368&dopt=Abstract clindamycin antibiotic Cleocin-T



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Clindamycin treatment of experimental chronic osteomyelitis due to Staphylococcus aureus.

Norden CW, Shinners E, Niederriter K.

Clindamycin was used alone for treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Treatment with 30 mg/kg of body weight three times a day for 14 days was ineffective in sterilizing infected rabbit bones. In contrast, when given for 28 days, clindamycin sterilized the infected bones of 16 (84%) of 19 rabbits treated. Only one of 14 isolates of S. aureus from rabbits treated for two weeks developed resistance to clindamycin (minimal inhibitory concentration, greater than 100 micrograms/ml); none of three isolates from rabbits in which treatment failed in the four-week treatment group showed resistance to clindamycin. The results of four weeks of treatment with clindamycin for chronic experimental staphylococcal osteomyelitis were significantly better than those obtained with any other single agent used in prior studies and were generally as good as those with combination therapy that included rifampin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3701108&dopt=Abstract clindamycin antibiotic Cleocin-T



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An electron microscopic study of the effect of clindamycin on adherence of Staphylococcus aureus to bone surfaces.

Mayberry-Carson KJ, Mayberry WR, Tober-Meyer BK, Costerton JW, Lambe DW Jr.

Discs of rabbit tibia, 5 mm thick, were utilized to study the adherence of Staphylococcus aureus to the bone surface in the presence and absence of clindamycin. Bacteria were grown in broth media containing the bone slices and varying concentrations of clindamycin. In the absence of the antibiotic, S. aureus adhered extensively to bone surfaces and formed large microcolonies which were surrounded by an amorphous matrix. In the presence of 0.025 micrograms/ml of clindamycin (0.1 MIC), S. aureus adhered less to bone surfaces, forming smaller and fewer microcolonies. In the presence of 0.0625 micrograms/ml of clindamycin (0.25 MIC), S. aureus adhered to the bone surfaces only sparsely, forming small microcolonies with very little matrix holding them together, and leaving very large areas of the bone surface uncolonized. In the presence of 0.125 micrograms/ml of clindamycin (0.5 MIC), bone surfaces were basically clean, with only one or two cells (no microcolonies) found in crevices and indentations of the bone surface. In the presence of 0.25 micrograms/ml (1 MIC) no bacteria adhered to the bone surfaces.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3713547&dopt=Abstract clindamycin antibiotic Cleocin-T



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Pharmacy initiatives to reduce clindamycin use.

Greene SA, Record KE, Rapp RP, Amerson AB, Bell RM, Piecoro JJ Jr.

The effectiveness of clinical pharmacists and attending physicians in altering the prescribing of metronidazole and clindamycin by resident physicians was evaluated, and the effect of these changes on antibiotic costs was determined. In July 1983, clinical pharmacists and attending physicians educated resident physicians about the efficacy and cost-effectiveness of substituting metronidazole for clindamycin in the treatment of intraabdominal and pelvic infections. A three-month educational program was implemented, which included distribution of a newsletter and involvement of clinical pharmacists in patient rounds. The use patterns of these drugs were then monitored for a 12-month period. A total of 425 treatment periods for 414 patients were reviewed, representing 91% of all therapy with metronidazole and clindamycin. Metronidazole use increased from 18.2% one month after implementation of the educational program to a plateau of 50% by November. Clindamycin expenditures decreased by more than 50% from the previous fiscal year, resulting in a savings of $33,469 to the pharmacy. The prescribing patterns of resident physicians were altered and cost savings were realized as a result of a comprehensive educational program that focused on substituting metronidazole for clindamycin. The program's success was enhanced because an equally efficacious agent was available and because of the participation of clinical pharmacists in patient rounds.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3717177&dopt=Abstract clindamycin antibiotic Cleocin-T



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Pharmacokinetics of intravenous clindamycin in newborn infants.

Koren G, Zarfin Y, Maresky D, Spiro TE, MacLeod SM.

We studied 12 newborn infants (gestational ages 26-39 wk [mean +/- SD, 30.6 +/- 4.7]; birth weight 640-2700 g, [mean, 1,322 +/- 688]; postnatal age 1-24 days [mean, 9.6 +/- 8.5]) who received clindamycin phosphate for suspected or proven necrotizing enterocolitis (ten patients) or suspected anaerobic septicemia (two patients) in doses of 3.2-11 mg/kg every six hours. Range of mean serum concentration of clindamycin at steady state was between 12.7 and 40 micrograms/ml (therapeutic range = 2-10 micrograms/ml). High concentrations could be attributed to elimination T1/2 (6.3 +/- 2.1 hr) 100% longer than in older children or adults. Clindamycin clearance (61.6 +/- 31.6 hr ml/kg/hr) was lower than in older children or adults. Because of the observed prolongation in T1/2 and correspondingly lower clearance, the IV dose of clindamycin in newborn infants should be reduced to 15-20 mg/kg/day given in four daily doses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3737273&dopt=Abstract clindamycin antibiotic Cleocin-T



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Influence of ampicillin, clindamycin, and metronidazole on faecal excretion of short-chain fatty acids in healthy subjects.

Hoverstad T, Carlstedt-Duke B, Lingaas E, Midtvedt T, Norin KE, Saxerholt H, Steinbakk M.

The faecal excretion of short-chain fatty acids (SCFAs) has been measured in groups of six healthy subjects before, during, and after they received the antibiotics clindamycin, ampicillin, or metronidazole perorally for 6 days. Intake of clindamycin reduced the median total concentration of SCFAs from 62.9 mmol/kg faeces (wet weight) to 7.3 mmol/kg (p less than 0.05). During therapy the relative amounts of acetic acid increased from 50% to 90% of the total concentration (p less than 0.05). Ampicillin reduced the median SCFAs concentration from 62.4 mmol/kg to 47.8 mmol/kg (p less than 0.05), whereas metronidazole did not change the SCFAs concentrations significantly. The SCFAs concentrations returned to normal within 5 weeks after the treatment in all subjects. Clindamycin was detected in high concentrations in faeces during therapy. Ampicillin was detected in only one faecal sample, which was from the only subject in the ampicillin group without detectable beta-lactamase activity in faeces. Metronidazole could not be detected in faeces from any subjects receiving this drug. Clindamycin and ampicillin, but not metronidazole, induce pronounced changes in faecal SCFAs, most likely reflecting severe changes in the colonic ecosystem. An antibiotic's influence on the colonic microflora may in part depend on its antimicrobial spectrum and the concentration of antimicrobially active drug in the gut.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3749800&dopt=Abstract clindamycin antibiotic Cleocin-T