Cleocin
In vitro activity of LY 333328 against anaerobic gram-positive bacteria.

Sillerstrom E, Wahlund E, Nord CE.

Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.

LY 333328 is a new semisynthetic glycopeptide with reported activity against aerobic Gram-positive cocci such as enterococci, pneumococci, streptococci and staphylococci. The present investigation was undertaken to determine the in vitro activity of LY 333328 against 178 Gram-positive anaerobic bacteria recently isolated from human infections. The activity was compared with that of vancomycin, teicoplanin, cefoxitin, imipenem, clindamycin and metronidazole. Peptostreptococci (48 strains): LY 333328, range 0.016-1.0 mg/l; vancomycin, 0.125-2.0 mg/l; teicoplanin, 0.032-2.0 mg/l; cefoxitin, 0.064-8.0 mg/l; imipenem, 0.016-0.064 mg/l; clindamycin, 0.016-1.0 mg/l; metronidazole, 0.125-8.0 mg/l. Propionibacterium acnes (31 strains): LY 333328, range 0.032-0.125 mg/l; vancomycin, 0.25-0.5 mg/l; teicoplanin, 0.25-0.5 mg/l; cefoxitin, 0.125-1.0 mg/l; imipenem, 0.032-0.064 mg/l; clindamycin, 0.016-0.064 mg/l; metronidazole, 32-> or =64 mg/l. Clostridium difficile (50 strains): LY 333328, range 0.016-2.0 mg/l; vancomycin, 0.5-4.0 mg/l; teicoplanin, 0.064-0.5 mg/l; cefoxitin, 64-128 mg/l; imipenem, 8.0 mg/l; clindamycin, 0.25-128 mg/l; metronidazole, 0.125-0.25 mg/l. Clostridium perfringens (49 strains): LY 333328, range 0.016-2.0 mg/l; vancomycin, 0.025-4.0 mg/l; teicoplanin, 0.064-4.0 mg/l; cefoxitin, 0.5-1.0 mg/l; imipenem, 0.016-0.5 mg/l; clindamycin, 0.008-1.0 mg/l; metronidazole, 1.0-4.0 mg/l. LY 333328 had an excellent in vitro activity against anaerobic Gram-positive bacteria.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10326737&dopt=Abstract clindamycin antibiotic Cleocin-T



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Evaluation of low-dose, extended-interval clindamycin regimens against Staphylococcus aureus and Streptococcus pneumoniae using a dynamic in vitro model of infection.

Lewis RE, Klepser ME, Ernst EJ, Lund BC, Biedenbach DJ, Jones RN.

University of Iowa Colleges of Pharmacy, Iowa City, Iowa 52242-1112, USA.

We have previously described the activity of low-dose clindamycin in extended-interval dosing regimens by determination of bactericidal titer in serum. In this study, we used a one-compartment in vitro dynamic infection model to compare the pharmacodynamics of clindamycin in three intravenous-dosing regimens (600 mg every 8 h [q8h], 300 mg q8h, and 300 mg q12h) against three clinical isolates of Staphylococcus aureus and two clinical isolates of Streptococcus pneumoniae. Test organisms were added to the central compartment of the model to yield a starting inoculum of 10(6) CFU/ml. Clindamycin was injected as a bolus into the central compartment at appropriate times over 48 h to simulate the q8h or q12h dosing regimens. Drug-free culture medium was then pumped through the system to mimic a half-life of 2.4 h. At predetermined time points during the experiment, samples were removed from the central compartments for colony count determination and drug concentration analysis. The rates of killing did not significantly differ among the three clindamycin dosing regimens against either S. aureus or S. pneumoniae (P = 0.88 or 0.998, respectively). Likewise, no significant differences in activities were detected among the three regimens against staphylococci (P = 0.677 and 0.667) or pneumococci (P = 0.88 and 0.99). Against an S. aureus isolate exhibiting inducible macrolide-lincosamide-streptogramin B resistance, none of the three clindamycin regimens prevented regrowth of the resistance phenotype in the model. In this model, clindamycin administered at a low dose in an extended-interval regimen (300 mg q12h) exhibited antibacterial activity equivalent to that of the 300- or 600-mg-q8h regimen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10428927&dopt=Abstract clindamycin antibiotic Cleocin-T



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

Mueller SC, Henkel KO, Neumann J, Hehl EM, Gundlach KK, Drewelow B.

Department of Clinical Pharmacology, Institute of Pharmacology and Toxicology, Universitat Rostock, Germany.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10442308&dopt=Abstract clindamycin antibiotic Cleocin-T



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Community-acquired and clindamycin-susceptible methicillin-resistant Staphylococcus aureus in children.

Frank AL, Marcinak JF, Mangat PD, Schreckenberger PC.

Department of Pediatrics, College of Medicine, University of Illinois at Chicago, USA.

BACKGROUND: Recognition of children with community-acquired (CA) infections caused by clindamycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) prompted a retrospective study in two Chicago hospitals conducted from 1987 through 1997. METHODS: Laboratory records of MRSA isolates, antibiotic susceptibilities and information from patient medical records were reviewed. RESULTS: One hundred eleven MRSA isolates from 103 children were studied with 51 isolates CA and 77 susceptible to clindamycin. The CA infections were less frequently associated with prior surgery (P = 0.0039) or a foreign body (P = 0.0001), and clindamycin-susceptible MRSA infections were less frequently associated with a foreign body (P = 0.001) compared with nosocomially acquired or clindamycin-resistant MRSA infections. Clindamycin-susceptible MRSA sources were mostly skin, wound or abscess (69%). Soft tissue diagnoses predominated (70%), but 16% were serious invasive infections. Ninety percent of clindamycin-susceptible MRSA were susceptible to erythromycin and/or trimethoprim-sulfamethoxazole. Antibiotic undertreatment (45%) or overtreatment (17%) of children with the clindamycin-susceptible MRSA occurred, but clindamycin appeared to be effective when used. CONCLUSION: The impact of these organisms could be substantial if they become more frequent or widespread. S. aureus is a potential pathogen in large numbers of pediatric patients; microbiologic evaluation and both presumptive and definitive treatment of all these children may need to be changed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10571437&dopt=Abstract clindamycin antibiotic Cleocin-T



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Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals.

Johnson S, Samore MH, Farrow KA, Killgore GE, Tenover FC, Lyras D, Rood JI, DeGirolami P, Baltch AL, Rafferty ME, Pear SM, Gerding DN.

Department of Medicine, Veterans Affairs Chicago Health Care System, Lakeside Division, and Northwestern University Medical School, IL 60611, USA. stu-johnson nwu.edu

BACKGROUND: Large outbreaks of diarrhea caused by a newly recognized strain of Clostridium difficile occurred in four hospitals located in different parts of the United States between 1989 and 1992. Since frequent use of clindamycin was associated with the outbreak in one of the hospitals, we examined the resistance genes of the epidemic-strain isolates and studied the role of clindamycin use in these outbreaks. METHODS: Case-control studies were performed at three of the four hospitals to assess the relation of the use of clindamycin to C. difficile-associated diarrhea. All isolates of the epidemic strain and representative isolates of other strains identified during each outbreak were tested for susceptibility to clindamycin. Chromosomal DNA from these representative isolates was also analyzed by dot blot hybridization and amplification with the polymerase chain reaction (PCR) with the use of probes and primers from a previously described determinant of erythromycin resistance - the erythromycin ribosomal methylase B (ermB) gene - found in C. perfringens and C. difficile. RESULTS: In a stratified analysis of the case-control studies with pooling of the results according to the Mantel-Haenszel method, we found that the use of clindamycin was significantly increased among patients with diarrhea due to the epidemic strain of C. difficile, as compared with patients whose diarrhea was due to nonepidemic strains (pooled odds ratio, 4.35; 95 percent confidence interval, 2.02 to 9.38; P<0.001). Exposure to other types of antibiotics or hospitalization in a surgical ward was not significantly associated with the risk of C. difficile-associated diarrhea due to the epidemic strain. All epidemic-strain isolates were highly resistant to clindamycin (minimal inhibitory concentration, >256 microg per milliliter). DNA hybridization and PCR analysis showed that all these isolates had an ermB gene, which encodes a 23S ribosomal RNA methylase that mediates resistance to macrolide, lincosamide, and streptogramin antibiotics. Only 15 percent of the nonepidemic strains were resistant to clindamycin. CONCLUSIONS: A strain of C. difficile that is highly resistant to clindamycin was responsible for large outbreaks of diarrhea in four hospitals in different states. The use of clindamycin is a specific risk factor for diarrhea due to this strain. Resistance to clindamycin further increases the risk of C. difficile-associated diarrhea, an established complication of antimicrobial use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10572152&dopt=Abstract clindamycin antibiotic Cleocin-T



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[Serotype distribution and antimicrobial susceptibility of group A streptococci (Streptococcus pyogenes) isolated in Taiwan]

[Article in Chinese]

Pan TM, Lin SS, Yu YL, Horng CB.

National Institute of Preventive Medicine, Department of Health, Taipei, Taiwan, R.O.C.

T-protein serotypes and antimicrobial susceptibility of a total of 139 group A streptococci (GAS) strains isolated in Taiwan area in 1993 and during the outbreak of scarlet fever in 1994 were analyzed. All strains were T-typable, and T12 (42.46%) and T4 (38.85%) were the dominant T types. According to the results of analysis of antimicrobial susceptibility, all GAS strains were divided into 9 resistotypes, A (all susceptible), B (resistant to tetracycline), C (resistant to erythromycin and tetracycline), D (resistant to chloramphenicol and tetracycline), E (resistant to chloramphenicol and clindamycin), F (resistant to chloramphenicol, clindamycin and tetracycline), G (resistant to clindamycin, erythromycin and tetracycline), H (resistant to chloramphenicol, clindamycin, erythromycin and tetracycline), and I (resistant to chloramphenicol, clindamycin, erythromycin, tetracycline and vancomycin). Type B (37.42%) was the dominant type. Type A (25.91%), and type H (26.63%) also appered with high incidence. Most of strains isolated from Mid-Taiwan were type H. Only one strain, that was isolated in I-lan, was resistant to vancomycin, in addition to resistant to chloramphenicol, clindamycin, erythromycin, and tetracycline. All strains were susceptible to penicillin G, ampicillin, and ceftriaxone. Some strains were resistant to chloramphenicol (32.38%), clindamycin (30.22%), erythromycin (31.66%), tetracycline (73.39%), and vancomycin (0.70%). During the outbreak of scarlet fever in 1994, the dominant T types of strains isolated in North-Taiwan and Mid-Taiwan were T4 and T12, respectively, and the major resistotypes of those strains were B and H types, respectively. These clues suggested that the outbreaks occurring in North-Taiwan and Mid-Taiwan may have no epidemiological linkage between each other.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10592797&dopt=Abstract clindamycin antibiotic Cleocin-T