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PubMed2006

Investigation of inducible clindamycin and telithromycin resistance in isolates of beta-hemolytic streptococci.

We evaluated the accuracy of an erythromycin-clindamycin double-disk test (D-zone test) and an erythromycin-telithromycin D-zone test for detection of inducible resistance in isolates of beta-hemolytic streptococci with erythromycin resistance. The results of these tests were compared to results of a broth microdilution (BMD) induction test using combinations of erythromycin and either clindamycin or telithromycin. Of 29 erythromycin-resistant, clindamycin-susceptible isolates, 16 were positive by the erythromycin-clindamycin D-zone test; all of these demonstrated inducible clindamycin resistance by BMD. Twelve isolates were D-zone test-negative, did not demonstrate inducible resistance by BMD, and were positive for a mef determinant. Of 39 erythromycin-resistant, telithromycin-susceptible isolates, 13 were erythromycin-telithromycin D-zone test-positive, 19 questionably positive (unclear blunting of the zone), and 7 were D-zone test-negative. The erythromycin-telithromycin D-zone test result did not correlate with inducible resistance by BMD or the presence of an erm or mef gene. These results demonstrate that the erythromycin-clindamycin D-zone and BMD induction tests accurately detect inducible clindamycin resistance, but the erythromycin-telithromycin D-zone test is not reliable for detecting inducible telithromycin resistance.

Anti-Bacterial Agents↗
PubMed2004

Differential effects of clindamycin on neutrophils of healthy donors and septic patients.

Antibiotics are frequently administered to ICU patients in case of bacterial infections. Little is known, however, about the interference of antibiotics with neutrophil host defence mechanisms in patients with sepsis and multiple organ dysfunction syndrome (MODS). With our study, evidence for differential clindamycin effects on neutrophils in healthy donors and septic patients without or with MODS was sought. Functional parameters (oxidative response and phagocytosis) and fMLP receptor expression were analysed. The study was approved by the local ethical board. Venous blood was drawn from healthy donors and septic patients. Neutrophils in PBS were incubated with 0, 5, 25 or 125 microg/ml clindamycin and analysed flow cytometrically. Neutrophils of patients with sepsis and MODS showed a significantly higher basal activation compared to healthy donors. Clindamycin application led to a dose-dependent significant suppression of the fMLP-induced oxidative response in patients with sepsis and MODS, but not in healthy donors or septic patients in the absence of MODS. In patients with sepsis and MODS, phagocytosis of Escherichia coli and Staphylococcus aureus was significantly suppressed by clindamycin 125 microg/ml. In both other treatment groups, clindamycin did not affect phagocytosis. fMLP receptor expression was not altered by clindamycin. High-dose clindamycin selectively suppresses functional responses of neutrophils in septic patients with MODS. Simultaneously applied drugs, such as general anaesthetics, may potentiate this modulation of antibacterial defence and inflammation.

Anti-Bacterial Agents↗
PubMed1982

Systemic absorption of clindamycin hydrochloride after topical application.

Clindamycin has become a highly popular drug for the topical therapy of acne; however, the extent to which it is systemically absorbed from the skin has has not been established. We measured the serum level and urinary excretion of clindamycin on the third day and the twenty-seventh day of therapy in thirteen patients who were applying 1% clindamycin hydrochloride topically for acne. There was no detectable antibiotic in the serum of any subject (less than 0.4 microgram/ml); in contrast, clindamycin was found in the urine of ten of the thirteen patients. There was marked intersubject variation in the urinary excretion of the drug, ranging from less than 10 to 500 micrograms/day. However, there was a highly significant correlation (p less than 0.0001) for a given subject between excretion values on days 3 and 27. There was no correlation between urinary excretion of clindamycin and either racial pigmentation or severity of acne in this relatively small group of patients. After topical application of 1% clindamycin hydrochloride, an average of 4% to 5% of clindamycin appears to be absorbed systemically, but greater amounts are absorbed in some individuals.

Acne Vulgaris↗
PubMed1999

Perioperative antibiotic prophylaxis in maxillofacial surgery: penetration of clindamycin into various tissues.

Although clindamycin is recommended for prophylactic use in oral and maxillofacial surgery, there is little data available regarding its ability to provide sufficient tissue concentrations at the operative site. We investigated tissue samples from 31 patients, who had to undergo oral and maxillofacial surgery and who received at least one dose of 600 mg clindamycin i.v. preoperatively, to determine clindamycin tissue concentrations in muscle, oral mucosa, fatty tissue, skin and bone between 15 min and 8 h after administration. After homogenization, clindamycin concentration was determined by bioassay. It was demonstrated that clindamycin concentrations above the MIC90 of those pathogens most likely to cause contamination were reached in all kinds of tissues investigated. Already 15 min after administration, tissue concentrations above the MIC90 were reached and were still detectable in the last samples taken between 4 and 8 h after the last clindamycin administration. From the pharmacokinetic point of view, clindamycin is suitable for perioperative prophylaxis during oral and maxillofacial surgery providing sufficient tissue concentrations with no intraoperative additional dosage necessary unless procedures exceed 4 h duration.

Absorption↗
PubMed2003

Reduction of viable bacteria in dentinal tubules treated with clindamycin or tetracycline.

AIM: We sought to evaluate and compare the antibacterial effect of clindamycin and tetracycline in bovine dentinal tubules. METHODS: Dentinal tubules of 32 cylindrical bovine root specimens were infected with Streptococcus sanguis N1. Clindamycin 2% or tetracycline 2% (Ledermix) was placed in the root canal for 1 week. Powder dentin samples obtained from within the canal lumina by using International Standards Organization No. 25 to No. 31 burs were examined for the presence of vital bacteria after the brain-heart infusion plates were inoculated and the colony-forming units were counted. The potent effect of the medicaments was also evaluated through the use of the agar diffusion test. RESULTS: Heavy bacterial infection was observed in the control bovine root specimens at the layer close to the lumen. This decreased rapidly from layer to layer up to the deepest layer tested (300-400 microm), which contained several hundred colony-forming units. Clindamycin significantly reduced the amount of viable bacteria in each dentin layer compared with the positive control and tetracycline (P <.01). The agar diffusion test, wherein dilutions in increments of 1/3 and 1/9 were used, revealed that both medicaments had antibacterial activity, but clindamycin was significantly better. In the 1/27 dilution, clindamycin had a minor effect and tetracycline had no effect at all. CONCLUSION: Under the experimental conditions used in this study, the commercial preparations of clindamycin were more effective than those of tetracycline (Ledermix) in the agar diffusion test and clindamycin penetrated into dentinal tubules up to 400 microm. Thus, it has the potential to serve as an effective intracanal medicament in persistent infections when other medicaments fail.

Analysis of Variance↗
PubMed2000

Clinical and economic impact of a pharmacist-intervention to promote sequential intravenous to oral clindamycin conversion.

A multicentre, prospective, controlled study compared the clinical efficacy, safety and economic impact of a pharmacist intervention to promote sequential intravenous to oral clindamycin conversion. A total of 473 patients receiving intravenous clindamycin for at least 72 hours were included in the study. Two groups were established: an intervention group (204 patients) in which an informative sheet recommending the sequential treatment was provided, and a control group (269 patients). Clindamycin was prescribed for respiratory infections in 38.9% and for prophylaxis in surgery in 25.4% of the patients (71% were contaminated surgery). No difference between groups regarding sex, infection severity, health status or clinical progress was observed. Both the step-down treatments after 72 hours of intravenous clindamycin and the change to the oral route later on, were significantly increased with the intervention (p < 0.001, p < 0.001 respectively). No significant differences between both groups were found in the number of patients with adverse effects associated with the i.v. therapy, although the incidence tended to be lower in the intervention group (49/204 intervention versus 85/269 control, p = 0.07). Compliance with the recommended clindamycin dosing regimen was significantly higher in the intervention group, in which 1.3 days reduction of intravenous therapy provided an average cost savings of PTA5246 (95% CI 2556-7935) per treatment. A higher reduction of 1.7 days was achieved in those patients candidates for switch therapy on the third day of intravenous clindamycin. A sequential program with clindamycin may provide a cost-effective alternative to conventional therapy and the introduction of an information sheet is a cost-effective strategy to promote it.

Administration, Oral↗
PubMed2002

Cutaneous adverse reactions to clindamycin: results of skin tests and oral exposure.

BACKGROUND: Clindamycin is an antibiotic used in anaerobic and severe complicated infections. It is often selected for patients with a history of allergy to other antibiotics. OBJECTIVES: To study the occurrence of clindamycin hypersensitivity and to determine whether skin tests are useful in cases of suspected clindamycin allergy. METHODS: Six patients with an exanthematous rash and a history strongly suggestive of clindamycin hypersensitivity were studied with skin tests and oral exposure. Cases of suspected adverse drug reactions to clindamycin reported to the National Register of Adverse Effects of Drugs (NRAED) in Finland during 1973-2000 were analysed. RESULTS: In the skin tests true-positive patch test reactions were seen in four of six patients, while 22 healthy control patients were negative. One false-positive and one false-negative patch test reaction were seen. During 1973-2000, 29 suspected cases of skin and/or mucosal membranes affected by clindamycin were reported to the NRAED. CONCLUSIONS: Clindamycin hypersensitivity is not common. Delayed-type allergic reactions occur and patch tests are useful in those cases. Oral exposure is the method of choice if possible, as false-negative and false-positive reactions may occur.

Administration, Oral↗
PubMed2000

Intraocular concentrations of clindamycin obtained by sequential parabulbar injections.

PURPOSE: To measure the intraocular concentration of Clindamycin that can be maintained by sequential injection through a retained parabulbar catheter. MATERIALS AND METHODS: The peak intraocular concentration and half-life of Clindamycin after parabulbar injection was determined in a rabbit model. In a second experiment a parabulbar catheter was inserted and the maximum concentration that could be maintained by sequential injection through the catheter at intervals of 6 hours was determined. In a third experiment both eyes of the rabbit were catheterized and one infused with Clindamycin. The eyes were enucleated and studied by light and electron microscopy for changes induced by Clindamycin and the catheter. RESULTS: The concentration of Clindamycin after a single parabulbar injection of 10 mg/kg peaked in the retina and choroid at 2 hours and was 336 micrograms/g. The serum level at 2 hours was 2.2 micrograms/ml. The half-life in choroid and retina was 1 hour. Sequential administration at 6 hour intervals maintained a minimum concentration of 87 micrograms/ml. The vitreous concentration was maintained at 2 micrograms/ml. CONCLUSION: The level of Clindamycin in the retina and choroid obtained by sequential injections of 10 mg/kg exceeds the minimum lethal dose for organisms susceptible to the drug. The low serum concentration suggests that sequential doses of Clindamycin by the parabulbar route might be an effective therapy for toxoplasmic retinochoroiditis and would diminish the risk of colitis or other deleterious systemic side effects.

Animals↗
PubMed2003

Efficacy and tolerability of combined topical treatment of acne vulgaris with adapalene and clindamycin: a multicenter, randomized, investigator-blinded study.

This multicenter, randomized, investigator-blinded study investigated the efficacy and tolerability of adapalene gel 0.1% plus clindamycin phosphate lotion 1%, compared with clindamycin plus vehicle for the treatment of mild to moderate acne vulgaris. A total of 249 patients applied clindamycin lotion twice daily and adapalene (125 patients) or vehicle gel (124 patients) once daily for 12 weeks. A significantly greater reduction of total (P <.001), inflammatory (P =.004) and noninflammatory lesions (P <.001) was seen in the clindamycin plus adapalene group than in the clindamycin plus vehicle group. These significant treatment effects were observed as early as week 4 for both noninflammatory and total lesion counts. Both treatment regimens were well tolerated. Although the worst scores for scaling (P <.05), dryness (P <.01), and stinging/burning (P <.05) were higher in the clindamycin plus adapalene group than in the clindamycin plus vehicle group in patients with moderate or severe irritation; in most cases these symptoms were of mild intensity.

Acne Vulgaris↗
PubMed2006

A single centre, open-label, cross-over study of pharmacokinetics comparing topical zinc/clindamycin gel (Zindaclin) and topical clindamycin lotion (Dalacin T) in subjects with mild to moderate acne.

Zinc/clindamycin gel (Zindaclin 1%) gel, is a new once-daily topical acne treatment (Strakan Ltd) containing clindamycin phosphate equivalent to 1% clindamycin and zinc acetate in a formulation, which leads to a reduced systemic absorption of clindamycin through the skin. The objective of the study was to compare the systemic absorption of clindamycin from zinc/clindamycin gel and clindamycin lotion (Dalacin T topical lotion, Pharmacia Ltd) after repeated twice-daily topical administration for two periods of 5 days with an intervening gap of 2 weeks in 24 subjects with mild to moderate acne. Plasma Cmax, and AUC0-12 of clindamycin measured after single and multiple applications of zinc/clindamycin gel were between 30% and 50% lower than for clindamycin lotion. As zinc/clindamycin gel is a topical treatment for acne, the lower systemic bioavailability may be beneficial because there may be a correspondingly lower risk of systemic events in zinc/clindamycin gel-treated subjects.

Acne Vulgaris↗
PubMed1993

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

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.

Biotransformation↗
PubMed2004

Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children.

BACKGROUND: Fosmidomycin is a new antimalarial drug with a novel mechanism of action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens of >or=4 days were required to achieve radical cure, prompting further research to identify and validate a suitable combination partner to enhance its efficacy. METHODS: We conducted a randomized, controlled, open-label study to evaluate the efficacy and safety of fosmidomycin combined with clindamycin (n=12; 30 and 5 mg/kg body weight every 12 h for 5 days, respectively), compared with fosmidomycin alone (n=12; 30 mg/kg body weight every 12 h for 5 days) and clindamycin alone (n=12; 5 mg/kg body weight every 12 h for 5 days) for the clearance of asymptomatic Plasmodium falciparum infections in schoolchildren in Gabon aged 7-14 years. RESULTS: Asexual parasites were rapidly cleared in children treated with fosmidomycin-clindamycin (median time, 18 h) and fosmidomycin alone (25 h) but slowly in children treated with clindamycin alone (71 h; P=.004). However, only treatment with fosmidomycin-clindamycin or clindamycin alone led to the radical elimination of asexual parasites as measured by day 14 and 28 cure rates of 100%. Asexual parasites reappeared by day 28 in 7 children who received fosmidomycin (day 14 cure rate, 92% [11/12; day 28 cure rate, 42% [5/12]). All regimens were well tolerated, and no serious adverse events occurred. CONCLUSION: The combination of fosmidomycin and clindamycin is well tolerated and superior to either agent on its own with respect to the rapid and radical clearance of P. falciparum infections in African children.

Antimalarials↗
PubMed1975

Pharmacokinetics of lincomycin and clindamycin phosphate in a canine model.

Linomycin and clindamycin phosphate were studed in a canine model in which acute biliary obstruction was produced during iv infusion of antibiotic. Hepatic and renal extraction, bilary and renal excretion, and concentrations in liver and kidney were measured. Total and nonesterified clindamycin were assayed. The antibiotics were taken up by the liver at similar rates; however; the rates of excretion and concentration in bile were significantly higher for lincomycin than for clindamycin. Biliary obstruction did not affect the concentration of either antibiotic in canalicular bile. Lincomycin was extracted by the kidneys and excreted into urine at a much higher rate than was clindamycin. Concentrations of nonesterified clindamycin in the hepatic vein were higher than those in the portal vein, an observation suggesting metabolic activation within the liver. This relation was reversed by bilary obstructon. The results in this canine model indicate a greater role for the kedney in the disposition of lincomycin than in that of clindamycin, major differences between the rates of biliary excretion of the two agents, and a probable change in the metabolism of clindamycin procued by acute bilary obstruction.

Animals↗
PubMed1984

Clindamycin activity against chloroquine-resistant Plasmodium falciparum.

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.

Chloroquine↗
PubMed1988

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

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.

Bacterial Toxins↗
PubMed1983

Alkalinization of the intralysosomal pH by clindamycin and its effects on neutrophil function.

Clindamycin is concentrated within human neutrophils and their lysosomes because the intralysosomal pH is highly acidic and this antibiotic behaves as a weak base. We have examined the ability of clindamycin to buffer (alkalinize) the intralysosomal pH and studied the consequences of alterations of lysosomal pH on neutrophil functions. At therapeutic concentrations of clindamycin (0.01 mM), we observed no effect on intralysosomal pH as monitored by the distribution and fluorescence of a weakly basic fluorescent probe 9-aminoacridine. However, at higher concentrations (1.0 mM), clindamycin alkalinized the intralysosomal pH and inhibited neutrophil lysosomal degranulation to several stimuli, and superoxide production in response to phorbol myristate acetate. Neutrophil locomotion was unaffected even at concentrations of clindamycin which increased the intralysosomal pH. We conclude that clindamycin accumulates in acidic neutrophil lysosomes and, at high concentrations, alkalinizes the intralysosomal pH. Coincident with lysosomal alkalinization there is inhibition of secretion and respiratory burst activity suggesting that intact lysosomal pH regulation is important for these functions. Clindamycin provides a useful tool to examine the relationships between weak base uptake, lysosomal pH and neutrophil functions.

Adult↗
PubMed1994

Comparison of cefoperazone plus sulbactam with clindamycin plus gentamicin as treatment for intra-abdominal infections.

This study compared the safety and efficacy of cefoperazone plus sulbactam with that of clindamycin plus gentamicin in the treatment of intra-abdominal infection. Seventy-six patients were included in the analysis of an open, randomized, comparative, single-site trial. Forty-seven patients received cefoperazone-sulbactam, and 29 patients received clindamycin plus gentamicin. Thirty-three patients (70%) who received cefoperazone-sulbactam and 15 patients (52%) who received clindamycin plus gentamicin were cured of infection, did not suffer a relapse within one month after the end of treatment, and did not receive any other antibiotics during the follow-up period (P = 0.17). In patients treated with cefoperazone-sulbactam there were four cases of superinfection, one patient had a prolonged prothrombin time, six patients had a poor response, two patients received antibiotics during follow-up, and one patient died during follow-up because of cancer. Treatment with clindamycin plus gentamicin was associated with five cases of superinfection, four patients had a poor response, four patients had a drug reaction, and one patient required antibiotics in the follow-up period. Serum levels of cefoperazone-sulbactam measured at one and three hours after dosing were consistent with earlier findings in normal volunteers. Two hundred and one pathogens were isolated, and 17 of 122 aerobic isolates (14%) were resistant to cefoperazone-sulbactam, and 17 of 122 (14%) were resistant to both clindamycin and gentamicin. Eleven of 79 (14%) anaerobic isolates were resistant to cefoperazone, none was resistant to cefoperazone-sulbactam, and 10 of 79 (13%) were resistant to clindamycin. The results of this study show that cefoperazone-sulbactam is an effective and safe alternative to clindamycin plus gentamicin in the treatment of intra-abdominal infections.

Abdomen↗
PubMed1977

Endocarditis treated with clindamycin: relapse and liver dysfunction.

Clindamycin was used to treat six patients with endocarditis because of allergy to penicillin in five, and an unfavorable clinical response to methicillin in one. Only one patient had an uneventful cure with clindamycin. Two had hepatotoxicity which resolved rapidly after clindamycin was stopped. Two patients, one of whom had an aortic prosthesis, had completed four to six weeks of clindamycin therapy when clinical relapse occurred and blood cultures were again positive for a clindamycin-sensitive isolate. A fifth patient had peptostreptococcal endocarditis. Despite a favorable initial clinical and bacteriologic response, blood cultures taken on the 20th day of therapy again grew the Peptostreptococcus. This relapse pathogen had become resistant to clindamycin and was 100-fold less sensitive than the initial isolate. The few conditions in which clindamycin is indicated for therapy of bacterial endocarditis are outlined.

Adult↗