Cleocin
Mucosal concentration and excretion of clindamycin by the human stomach.

Hextall A, Radley S, Andrews JM, Boyd EJ, Dent JC, Donovan I, Wise R.

Department of Surgery, Dudley Road Hospital, Birmingham, UK.

Each of 12 patients undergoing routine diagnostic upper gastrointestinal endoscopy received a single iv infusion of clindamycin phosphate 300 mg over 10 min. During the endoscopy, mucosal biopsies of the gastric antrum and fundus were obtained at varying times following the infusion. The clindamycin concentrations in the biopsies and in serum samples also taken after the infusion were determined. In addition, six healthy volunteers participated in a cross-over study on two different days. On both days, each subject received a single iv infusion of clindamycin phosphate 300 mg, immediately after which, gastric secretion was stimulated by iv pentagastrin (2 micrograms/kg/h) which was infused continuously over 150 min. On one of the study days, acid secretion by the stomach was inhibited by a slow iv infusion of ranitidine 50 mg. Clindamycin concentrations in gastric aspirates and serum samples collected after the infusion were determined. Concentrations of clindamycin in the fundal mucosa were significantly higher than the simultaneous serum concentrations (median ratio of tissue concentration to serum concentration, 2.0; P < 0.005) while concentrations in the antral mucosa were similar to those in serum (median ratio, 1.2; P = 0.65). Ranitidine significantly inhibited pentagastrin-stimulated acid secretion as demonstrated by a decrease in the volume of gastric aspirate when ranitidine was administered compared with when it was not administered (P < 0.01). Clindamycin concentrations in gastric juice were approximately one and one-half times higher than those in serum samples obtained simultaneously, both during stimulation of gastric acid secretion with pentagastrin and during inhibition of pentagastrin-stimulated acid secretion with ranitidine. Gastric juice concentrations of clindamycin were significantly higher following administration of ranitidine than after stimulation of gastric secretion by pentagastrin alone. Fundal mucosal and gastric juice concentrations of clindamycin exceeded the hypothetical maximum serum concentrations, indicating that accumulation in the stomach occurred against a concentration gradient.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8040123&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Differential inhibition by clindamycin on slime formation, adherence to teflon catheters and hemolysin production by Staphylococcus epidermidis.

Shibl AM, Ramadan MA, Tawfik AF.

Division of Microbiology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Slime formation was detected in Staphylococcus epidermidis strains isolated from either infected patients or healthy individuals. Cells of S. epidermidis, that either formed slime or not, adhered to teflon catheters. There was no correlation between adherence of bacteria to teflon catheters and slime formation. Clindamycin at subinhibitory concentration significantly inhibited slime formation without inhibiting bacterial growth. Adherence of S. epidermidis to teflon catheters was affected by the presence of clindamycin whether slime was produced or not. Clindamycin at subinhibitory concentrations markedly inhibited hemolysin production by S. epidermidis without appreciably altering the cell density, and cells grown in the presence of the drug showed very low hemolytic activity upon disruption. These results suggest that clindamycin at low concentration alters S. epidermidis virulence properties, apart from inhibiting growth.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8077984&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Decrease in nosocomial Clostridium difficile-associated diarrhea by restricting clindamycin use.

Pear SM, Williamson TH, Bettin KM, Gerding DN, Galgiani JN.

Veterans Affairs Medical Center, Tucson, AZ.

OBJECTIVE: To report the investigation and effective control of a nosocomial epidemic of Clostridium difficile-associated diarrhea. DESIGN: Concurrent surveillance for identification of new nosocomial cases, retrospective case-control analysis, and hospital formulary control of antibiotic use. SETTING: University-affiliated Veterans Affairs Medical Center located in southwestern United States. PATIENTS: Hospitalized patients who developed diarrhea submitted stool specimens for cytotoxin assay. Patients who were positive for cytotoxin were compared with control patients without infection. MEASUREMENTS: Isolates of C. difficile were typed by restriction endonuclease analysis. Antimicrobial agent use from hospital pharmacy records and selected patient data from chart review were correlated with frequency of specific laboratory abnormalities. RESULTS: For 13 months, the monthly incidence of C. difficile infection averaged more than five times that for the previous 21 months. Stool specimens from 34 patients (59%) contained a single strain (restriction enzyme analysis type J7). Clindamycin was statistically associated with the epidemic as shown by the following: clindamycin use at our center compared with national normal values, clindamycin use for years before compared with during the epidemic, monthly use of clindamycin compared with monthly frequency of infection, frequency of infection in patients receiving clindamycin compared with that in patients receiving other antimicrobial agents, and amount of clindamycin used by infected patients compared with that used by control patients. Restricting clindamycin use led to a prompt disease in infection rate and the type J7 organisms. CONCLUSION: A nosocomial epidemic of C. difficile diarrhea was controlled by analysis of antibiotic use patterns and by subsequent restriction of clindamycin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8080497&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin.

Pfefferkorn ER, Borotz SE.

Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755-3842.

Azithromycin and spiramycin markedly inhibited the growth of Toxoplasma gondii in cultured human fibroblasts. However, 3 days of treatment were required to reveal their full antitoxoplasma activity. This delayed onset of inhibition was similar to that previously reported for clindamycin. Mutants of T. gondii resistant to azithromycin (AziR-1) and spiramycin (SprR-1) were isolated and compared with a previously described mutant resistant to clindamycin (ClnR-2). Mutant ClnR-2 was cross-resistant to all three antibiotics, while AziR-1 was cross-resistant only to spiramycin and SprR-1 was cross-resistant only to azithromycin. In short-term studies of protein synthesis by freshly prepared extracellular parasites, clindamycin and azithromycin were effective only at concentrations much greater than their 50% inhibitory concentrations in infected cultures and the resistant mutants did not differ from the wild type in antibiotic sensitivity. Thus, protein synthesis on cytoplasmic ribosomes of the parasite did not seem to be the target of these antibiotics. To determine whether mitochondrial protein synthesis in T. gondii was inhibited by clindamycin or azithromycin, wild-type parasites were grown in cultured cells in the presence of antibiotic concentrations well above the 50% inhibitory concentrations. Mitochondrial function, measured by oxygen uptake per purified extracellular parasite, did not decrease substantially, after the parasites had multiplied 11-fold in the presence of antibiotic. Thus, mitochondrial protein synthesis did not seem to be the target of clindamycin or azithromycin. An alternative target is protein synthesis in the putative apicomplexan organelle that has a 35-kb genome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8141576&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Detection of multiple macrolide- and lincosamide-resistant strains of Streptococcus pyogenes from patients in the Boston area.

Hasenbein ME, Warner JE, Lambert KG, Cole SE, Onderdonk AB, McAdam AJ.

Department of Laboratory Medicine, Children's Hospital Boston and Harvard Medical School, Massachusetts 02115, USA.

Macrolide (including erythromycin and azithromycin) and lincosamide (including clindamycin) antibiotics are recommended for treatment of penicillin-allergic patients with Streptococcus pyogenes pharyngitis. Resistance to erythromycin in S. pyogenes can be as high as 48% in specific populations in the United States. Macrolide and lincosamide resistance in S. pyogenes is mediated by several different genes. Expression of the erm(A) or erm(B) genes causes resistance to erythromycin and inducible or constitutive resistance to clindamycin, respectively, whereas expression of the mef(A) gene leads to resistance to erythromycin but not clindamycin. We studied the resistance of S. pyogenes to erythromycin and clindamycin at an urban tertiary-care hospital. Of 196 sequential isolates from throat cultures, 15 (7.7%) were resistant to erythromycin. Three of these were also constitutively resistant to clindamycin and had the erm(B) gene. Five of the erythromycin-resistant isolates were resistant to clindamycin upon induction with erythromycin and had the erm(A) gene. The remaining seven erythromycin-resistant isolates were susceptible to clindamycin even upon induction with erythromycin and had the mef(A) gene. Pulsed-field gel electrophoresis analysis and emm typing demonstrated that the erythromycin-resistant S. pyogenes comprised multiple strains. These results demonstrate that multiple mechanisms of resistance to macrolide and lincosamide antibiotics are present in S. pyogenes strains in the United States.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15071004&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Activity of fleroxacin alone and in combination with clindamycin or metronidazole in experimental intra-abdominal abscesses.

Pefanis A, Thauvin-Eliopoulos C, Holden J, Eliopoulos GM, Ferraro MJ, Moellering RC Jr.

Department of Medicine, New England Deaconess Hospital, Boston, MA 02215.

To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to stimulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen. After 8.5 days of therapy, final bacterial counts in abscesses showed that fleroxacin alone or combined with metronidazole or clindamycin effectively eradicated Escherichia coli, with bacterial densities of < or = 2.84 +/- 0.1, < or = 2.9 +/- 0.1, and < or = 2.9 +/- 0.1 (mean +/- standard error of the mean) log10 CFU/g, respectively. The addition of either clindamycin or metronidazole to fleroxacin substantially enhanced the effectiveness of the regimens against Bacteroides fragilis, with bacterial counts of < or = 3.0 +/- 0.1 or < or = 2.9 +/- 0.1 log10 CFU/g, respectively, versus 9.2 +/- 0.2 log10 CFU/g for fleroxacin alone. The combination of metronidazole and fleroxacin also resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (< or = 2.9 +/- 0.1 versus 6.1 +/- 0.9 log10 CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log10 CFU/g, respectively). Except for those of B. fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active a clindamycin plus gentamicin against all species and was significantly more active against Clostridium spp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or clindamycin would effectively enhance the spectrum of fleroxacin for treatment of mixed aerobic and anaerobic infections.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8192453&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Different kinetic of enzymatic inactivation of lincomycin and clindamycin in Staphylococcus aureus.

Barcs I.

Department of Bacteriophages, B. Johan National Institute of Hygiene, Budapest, Hungary.

Lincosamide inactivation nucleotidylation (Lin) enzyme determined by the pBI109PGL plasmid of Staphylococcus epidermidis exhibits high level resistance to lincomycin but sensitivity to clindamycin by standard susceptibility methods. Substrate profile determination showed clindamycin to be a better substrate for the enzyme than lincomycin. In cultures of the plasmid-harboring strain, the level of clindamycin decreased below the inhibitory concentration in the first 4 hours of incubation but the level of lincomycin persisted longer. The initial extended inhibitory effect of clindamycin is due to better membrane penetrating ability, resulting in a higher intracellular concentration than that of lincomycin. Moreover, energy-dependent reduction in clindamycin uptake, probably due to active efflux of clindamycin but not of lincomycin, was observed. A therapeutic effect of clindamycin is not expected in infections caused by Lin-producer strains because the bacteriostatic effect of the drug is rapidly eliminated after administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8229148&dopt=Abstract clindamycin antibiotic Cleocin-T