Cleocin
Influence of clindamycin on fibronectin-staphylococcal interactions.

Doran JE, Rissing JP.

This report examines the effects of subinhibitory concentrations of of clindamycin on fibronectin-staphylococcal interactions. Using in-vitro binding assays, exposure of staphylococci to subinhibitory concentrations of clindamycin results in a dose-dependent decrease in fibronectin's ability to bind to treated organisms. Concomitant with decreased fibronectin binding is a decreased ability for fibronectin to mediate the phagocytosis of treated organisms by human polymorphonuclear leukocytes. Serum-mediated phagocytosis of clindamycin-treated organisms remained effective despite the reduction in fibronectin binding capabilities. These results suggest that the clinical use of clindamycin has the potential to affect bacterial binding of fibronectin, thus modifying the adherence of organisms to host surfaces without adversely effecting their clearance by the reticuloendothelial system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6315672&dopt=Abstract clindamycin antibiotic Cleocin-T



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Effect of clindamycin on growth and haemolysin production by Escherichia coli.

Boe NM, Dellinger EP, Minshew BH.

The effect of clindamycin on growth and haemolysin production by four strains of Escherichia coli was tested. Clindamycin MICs were greater than 256 mg/l for all strains. Clindamycin concentrations of 16-256 mg/l significantly inhibited growth, while concentrations from 2-32 mg/l significantly inhibited haemolysin production. Administration of clindamycin to rats with peritonitis due to haemolytic E. coli reduced mortality. Subinhibitory concentrations of clindamycin can inhibit growth and haemolysin production by E. coli and reduce mortality in an animal model of haemolytic E. coli peritonitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6358179&dopt=Abstract clindamycin antibiotic Cleocin-T



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Synthesis and antimicrobial activity of clindamycin analogues: pirlimycin, 1,2 a potent antibacterial agent.

Birkenmeyer RD, Kroll SJ, Lewis C, Stern KF, Zurenko GE.

The preparation of a series of analogues of clindamycin is described in which the naturally occurring five-membered cyclic amino acid amide portion of the molecule is replaced by a four-, six-, or seven-membered cyclic amino acid amide. The most interesting compound is pirlimycin (7e, U-57,930E), in which the (2S-trans)-4-n-propylhygramide portion of clindamycin is replaced by (2S-cis)-4-ethylpipecolamide. This structural modification results in significantly favorable changes in toxicity, metabolism, and antibacterial potency. Although the in vitro antibacterial activity of clindamycin and pirlimycin are nearly identical, the latter compound is 2-20 times more active than clindamycin when administered to mice experimentally infected with strains of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Bacteroides fragilis, and Plasmodium berghei. Pirlimycin is absorbed in rats and mice following both subcutaneous and oral administration. It readily penetrates B. fragilis induced abscesses in mice and is sequestered within these abscesses. A drug concentration of at least 60 times the required inhibitory concentration is maintained for 6 h following a single subcutaneous dose of 200 mg/kg. Urinary excretion of total bioactivity consists only of intact pirlimycin with no other antibacterially active metabolites being detected. Pirlimycin is tolerated well in rats and mice at the administered levels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6363698&dopt=Abstract clindamycin antibiotic Cleocin-T



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Interaction of subminimal inhibitory concentrations of clindamycin and Escherichia coli: effects on adhesion and polymorphonuclear leukocyte function.

Bassaris HP, Lianou PE, Papavassiliou JT.

Subinhibitory concentrations (sub-MICs) of clindamycin interfere with the adhesion of Escherichia coli to buccal epithelial cells and promote phagocytosis and killing of this organism by human polymorphonuclear leukocytes (PMNLs). Adherence of E. coli grown in the presence of clindamycin, at concentrations of 2-32 mg/l, varied from 21.1 +/- 7.4 to 25.8 +/- 7.8 bacteria per epithelial cell (EC) (mean +/- S.D.) as compared with 58.3 +/- 10.3 per EC when the organism was cultured in the absence of the antibiotic (P less than 0.01). The number of phagocytosed bacteria per 200 PMNLs increased from 166.1 +/- 36.6 when E. coli was grown in medium 199 containing no antibiotic, to 289.3 +/- 56.4 (P less than 0.01) when the organism was preincubated with 4 mg/l of clindamycin. The same concentration of clindamycin also increased the percentage of phagocytosed bacteria killed by the PMNLs from 42.0 +/- 9.0% to 63.7 +/- 11.2% (P less than 0.01). The results of this study indicate that sub-MICs of clindamycin enhance host-defence mechanisms against E. coli.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6373717&dopt=Abstract clindamycin antibiotic Cleocin-T



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Clindamycin activity against chloroquine-resistant Plasmodium falciparum.

Seaberg LS, Parquette AR, Gluzman IY, Phillips GW Jr, Brodasky TF, Krogstad DJ.

The clindamycin dose-response curves observed with both chloroquine-resistant and chloroquine-susceptible strains of Plasmodium falciparum in vitro demonstrated a plateau region that extended from 10(-2) to 10(1) micrograms/ml of drug (22 nM to 22 microM). Similar dose-response curves were also observed with the three major metabolites of clindamycin (clindamycin sulfoxide, de-N-methyl clindamycin, and de-N-methyl clindamycin sulfoxide). The position of this plateau was time dependent and rose from 20%-25% to 90%-95% inhibition of parasite growth between 24 and 72 hr of exposure to the drug. Clinidamycin treatment reduced plasmodial protein and nucleic acid synthesis (as measured by the incorporation of [3H]isoleucine and [3H]hypoxanthine, respectively) but did not interfere with knob formation. The combination of quinine plus a fixed concentration of clindamycin (0.1 microgram/ml) inhibited growth of the quinine-resistant Indochina I strain, although most of the antiplasmodial activity observed at quinine concentrations less than 50 ng/ml (154 nM) could be attributed to clindamycin alone.

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Influence of clindamycin on derepression of beta-lactamases in Enterobacter spp. and Pseudomonas aeruginosa.

Sanders CC, Sanders WE Jr, Goering RV.

Previous studies in this and other laboratories have shown that derepression of beta-lactamases in strains of Enterobacter and Pseudomonas spp. is responsible for the rapid development of resistance to a variety of beta-lactam antibiotics. The purpose of the current study was to evaluate the effects of clindamycin on derepression of beta-lactamases in these two genera. In tests with four strains of each genus, clindamycin diminished derepression in one isolate of each genus and completely prevented derepression in a second Enterobacter isolate (strain 55). Additional tests with strain 55 revealed that other inhibitors of macromolecular synthesis did not completely prevent derepression of beta-lactamase when tested at concentrations that did not inhibit replication. However, clindamycin did not affect synthesis of beta-lactamase that was constitutively produced in a mutant of this strain (55M). It also did not inhibit derepression of beta-galactosidase in either strain 55 or 55M. Clindamycin did not diminish the bactericidal effects of beta-lactam antibiotics against Enterobacter or Pseudomonas spp. However, it enhanced the bactericidal activity of cefamandole against strain 55. These in vitro effects of clindamycin on strain 55 that were related to prevention of derepression of beta-lactamase were confirmed in vivo with an animal model of infection. These results indicate that in some strains, clindamycin can specifically prevent derepression of beta-lactamases without inhibiting growth. Such a selective effect may provide a new approach for the enhancement of the antibacterial activity of certain beta-lactam antibiotics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6414365&dopt=Abstract clindamycin antibiotic Cleocin-T