Cleocin
Characterization of a nosocomial Clostridium difficile outbreak by using plasmid profile typing and clindamycin susceptibility testing.

Clabots CR, Peterson LR, Gerding DN.

Department of Medicine, Veterans Administration Medical Center, Minneapolis, Minnesota.

The mean number of cases of Clostridium difficile diarrhea at the Minneapolis Veterans Administration Medical Center increased to 17.3 per month in June-August 1985, compared with 7.1 per month in the previous 17 mo. Plasmid profiles and clindamycin susceptibility were used as markers to evaluate the increase in cases. Ninety clindamycin-resistant and 22 clindamycin-susceptible isolates of C. difficile from 1985 were examined for plasmids. A clindamycin-resistant organism contained a cryptic plasmid of 3.1 kilobases (kb). None of the clindamycin-susceptible isolates contained the 3.1-kb plasmid, as compared with 40 of 90 clindamycin-resistant isolates (P less than .005). Restriction endonuclease digestion and Southern blot hybridization were used to confirm the identity of the 3.1-kb plasmid between strains. Isolates retained clindamycin resistance after plasmid curing. It could not be determined if the organism responsible was an indigenous C. difficile strain that acquired a plasmid or was a new strain introduced from outside the hospital.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2844914&dopt=Abstract clindamycin antibiotic Cleocin-T



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Inactivation of lincosaminide antibiotics in Staphylococcus. Identification of lincosaminide O-nucleotidyltransferases and comparison of the corresponding resistance genes.

Brisson-Noel A, Delrieu P, Samain D, Courvalin P.

Unite des Agents Antibacteriens, Centre National de la Recherche Scientifique UA 271, Institut Pasteur, Paris, France.

Resistance to lincomycin by inactivation has been detected in numerous clinical isolates of Staphylococcus; in crude extracts of Staphylococcus haemolyticus BM4610 and Staphylococcus aureus BM4611, inactivation of lincomycin and clindamycin requires the presence of a nucleoside 5'-triphosphate (ATP, GTP, CTP, or UTP) as nucleotidyl donor and Mg2+ as cofactor. The biochemical mechanism of lincosaminide inactivation was elucidated by determination of the structure of inactivated lincomycin and clindamycin by physicochemical techniques, including UV absorption spectrophotometry, 31P and 1H nuclear magnetic resonance, and periodate oxidation. In the two strains, inactivation of lincomycin gave rise to lincomycin 3-(5'-adenylate), whereas clindamycin was inactivated through its conversion to clindamycin 4-(5'-adenylate). The gene linA' encoding the 3-lincomycin, 4-clindamycin O-nucleotidyltransferase in S. aureus BM4611 has been sequenced and displays 93% homology with the gene linA encoding the 3-lincomycin, 4-clindamycin O-nucleotidyltransferase found in S. haemolyticus BM4610. The two enzymes are 161 amino acids long and differ by 14 amino acid substitutions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2846528&dopt=Abstract clindamycin antibiotic Cleocin-T



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Effect of clindamycin on neutrophil killing of gram-negative periodontal bacteria.

Baker PJ, Wilson ME.

Department of Oral Biology, State University of New York, Buffalo 14214.

Periodontal diseases are infections of the tissues supporting the dentition. Recognition that relatively specific microfloras are associated with distinct clinical forms of periodontal disease has prompted the use of antimicrobial agents as adjuncts in periodontal therapy. Clindamycin is one of several antibiotics known to concentrate in bioactive form in neutrophils and to potentiate phagocyte bactericidal activity against certain bacteria. Neutrophils appear to play a key role in host defense against periodontopathic gram-negative bacteria. In the present study, we evaluated the effect of preincubation of neutrophils with therapeutically achievable concentrations of clindamycin upon subsequent in vitro bactericidal activity against three species of gram-negative periodontal bacteria, including Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga ochracea. In each instance, clindamycin neither enhanced nor inhibited the kinetics of bactericidal activity at low bacterium-neutrophil multiplicities. Further, this antibiotic had no demonstrable effect upon neutrophil bactericidal capacity, as assessed at bacterium-neutrophil ratios as high as 50:1. Our results indicate that clindamycin does not potentiate neutrophil bactericidal activity against the species of gram-negative periodontal organisms tested.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3056238&dopt=Abstract clindamycin antibiotic Cleocin-T



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In-vitro and in-vivo bacterocodal interactions of clindamycin and ceftazidime, by non-beta-lactamase mechanisms, in experimental Pseudomonas aeruginosa endocarditis caused by a constitutive beta-lactamase overproducing strain.

Bayer AS, Lindsay P, Parr TR Jr.

Department of Medicine, Harbor-UCLA Medical Center, Torrance 90509.

We studied a ceftazidime-resistant strain of Pseudomonas aeruginosa (PA-48) stably-derepressed for constitutive beta-lactamase overproduction, and its ceftazidime-susceptible parent (PA-96) in order to characterize the ability of clindamycin to: (1) enhance the in-vitro and in-vivo bactericidal activities of ceftazidime for PA-48; and (2) prevent beta-lactamase induction and spontaneous mutation to the derepressed state by the parental strain (PA-96). In vitro, clindamycin synergistically enhanced the bactericidal activity of ceftazidime vs PA-48. In the experimental aortic endocarditis model, the combination of clindamycin with ceftazidime significantly reduced mean intravegetation bacterial densities of PA-48 versus ceftazidime monotherapy and untreated controls at therapy days 6 and 11 (P less than 0.05). Exposure of growing PA-48 cells to clindamycin did not interfere with the hydrolytic function of extracted periplasmic beta-lactamase. Moreover, clindamycin did not suppress cefoxitin-mediated beta-lactamase induction in the parental strain (PA-96). In vitro, clindamycin prevented spontaneous mutation of PA-96 to the stably-derepressed state for beta-lactamase overproduction and also enhanced reversion of derepressed cells of PA-48 to the ceftazidime-susceptible parental phenotype by approximately 2 log10 cfu/ml. This latter effect was mirrored in vivo during clindamycin+ ceftazidime therapy of experimental endocarditis due to strain PA-48, as the proportion of ceftazidime-susceptible cells with vegetations increased by approximately 1-1.5 log10 cfu/g, versus untreated controls or ceftazidime monotherapy recipients. After clindamycin treatment ceased, vegetations contained predominantly ceftazidime-resistant variants. Clindamycin appeared to enhance bactericidal effects of ceftazidime vs PA-48 through non-beta-lactamase mechanisms probably involving promotion and maintenance of spontaneous reversion to the fully-repressed state. However, the concentrations of clindamycin required to achieve these effects are unlikely to be sustained at normal therapeutic dosage.

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Treatment of toxoplasmic encephalitis with intravenous clindamycin.

Dannemann BR, Israelski DM, Remington JS.

Department of Immunology and Infectious Diseases, Research Institute, Palo Alto, CA 94301.

At present, therapy for toxoplasmic encephalitis (TE) is the combination of pyrimethamine with sulfadiazine or trisulfapyrimidines. Unfortunately, due to adverse reactions to sulfonamides, many patients with acquired immunodeficiency syndrome (AIDS) are unable to receive a complete course of therapy. The promising results with clindamycin phosphate therapy in a mouse model of TE prompted us to seek further information about patients with AIDS with TE who had been treated with clindamycin. Fifteen such patients were identified in whom clindamycin was used to treat 18 episodes of TE. Eleven patients showed clinical or radiologic improvement after receiving clindamycin therapy, either alone or in combination with pyrimethamine. Twelve received oral clindamycin as suppressive therapy after discharge from the hospital. Adverse reactions possibly related to clindamycin therapy included diarrhea, reversible granulocytopenia, and skin reactions. The results of this retrospective study suggest that clindamycin, either alone or in combination with pyrimethamine, may represent an effective alternative therapy for TE in patients with AIDS. Whether this supposition can be substantiated by appropriately designed studies is presently being determined.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3190380&dopt=Abstract clindamycin antibiotic Cleocin-T



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Clindamycin pharmacokinetics and tissue penetration after head and neck surgery.

Stoehr GP, Yu VL, Johnson JT, Antal EJ, Townsend RJ, Wagner R.

Department of Pharmacy Practice, University of Pittsburgh, PA 15261.

Penetration of clindamycin into surgical wounds was studied in 10 patients undergoing radical head and neck surgery. Patients received one preoperative and three postoperative intravenous doses of clindamycin 600 mg. During surgery, samples of plasma and sternocleidomastoid muscle were obtained. Additional plasma samples were collected just before the fourth dose of clindamycin, just after that dose was infused, and 1, 2, 4, 6, 8, and 12 hours after dosing. Samples of wound exudate were collected at 2, 4, 6, 8, and 12 hours after the fourth dose. The muscle, plasma, and wound exudate samples were assayed for clindamycin base by a gas-liquid chromatographic method. Plasma and wound exudate samples obtained during surgery and one and eight hours after the fourth dose were assayed by a radial immunodiffusion technique for content of alpha 1-acid glycoprotein (AAG), the major binding protein for clindamycin. Pharmacokinetic values for plasma and wound drainage were calculated and compared. Concentrations of clindamycin in muscle (three to six hours after the first dose) ranged from 0.6 to 5.1 micrograms/g; the ratio of tissue to plasma concentrations ranged from 0.24 to 0.82. The highest mean clindamycin concentration in wound drainage was 4.9 micrograms/mL after the fourth dose, approximately 90% of simultaneous plasma concentrations. Concentrations in wound exudate exceeded those measured in plasma four hours after the dose, and elimination from the wound was slower than from plasma. AAG concentrations in plasma increased from a mean of 89 mg/dL intraoperatively to 134 mg/dL postoperatively. AAG was present in wound exudate in concentrations that were approximately 53% of those observed in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3197381&dopt=Abstract clindamycin antibiotic Cleocin-T