Cleocin
Occurrence of clindamycin-resistant anaerobic bacteria isolated from cultures taken following clindamycin therapy.

Ohm-Smith MJ, Sweet RL, Hadley WK.

MICs of clindamycin were determined by the agar dilution method against anaerobic organisms isolated from endometrial cultures in women with pelvic soft tissue infections. Cultures were obtained from 100 women both before and after clindamycin therapy, from 107 women before therapy with clindamycin or another antimicrobial agent or after treatment with an antimicrobial agent other than clindamycin, and from 9 women 1 to 9 weeks after they were discharged from the hospital following clindamycin therapy. Only 5 (0.7%) of 685 isolates tested from women who had not received clindamycin therapy were resistant to clindamycin. From the 100 cultures taken immediately after clindamycin therapy, 57 anaerobic bacteria were isolated from 28 cultures. Of the 40 anaerobic organisms for which MICs of clindamycin were determined, 25 (62.5%) were resistant to clindamycin (MIC greater than or equal to 8 micrograms/ml). The most common organisms isolated after therapy were the anaerobic gram-positive cocci (of which 32 isolates were discovered); of 28 coccal isolates tested, 64% were clindamycin resistant. Four of seven (57%) of the Bacteroides isolates tested, one unidentified gram-positive nonsporing rod, one unidentified gram-negative coccus, and one Mobiluncus sp. were also clindamycin resistant. Of 18 anaerobic isolates from the nine cultures taken 1 to 9 weeks after hospital discharge, 55% were resistant to clindamycin. The clinical significance of these findings is unknown since all patients recovered without incident and remained well. However, the data suggest that physicians need to be aware that patients with recent exposure to clindamycin may have clindamycin-resistant anaerobic organisms in a current infection. This may prevent the infection from responding to clindamycin treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3752973&dopt=Abstract clindamycin antibiotic Cleocin-T



Cleocin
Effects of muramyl dipeptide and clindamycin in a murine abdominal abscess model.

Cheadle WG, Brown GL, Lamont PM, Trachtenberg LS, Polk HC Jr.

Peritonitis and subsequent local and remote complications are an important source of morbidity and mortality, which persist despite the best available treatment. Reasonable therapeutic efforts, therefore, have included stimulation of host defenses with immune adjuvants, recently typified by muramyl dipeptide (MDP). Murine abdominal abscesses were created by intraperitoneal injection of Bacteroides fragilis and autoclaved fecal suspensions, and the effects of MDP and clindamycin on these abscesses were evaluated. At 10(4) colony-forming units (CFU) per milliliter of Bacteroides fragilis, intraperitoneal clindamycin was effective in reducing both the incidence of abscess formation as well as the number of abscesses per mouse as compared with controls at doses of 5 mg/kg and 2 mg/kg (P less than 0.01). The effect was more significant when the drug was given 30 min prior than when given after injection of organisms (P less than 0.02). At 10(7) and 10(8) CFU/ml, pretreatment with MDP increased abscess formation (P less than 0.05, P less than 0.01), an effect that was obscured by clindamycin administration, which decreased number of abscesses from controls irrespective of pretreatment with MDP. Abscesses were present on the third day after injection, and MDP, paradoxically, had increased the number of abscesses by the fifth day. Clindamycin reduced abscess formation at all concentrations of bacteria and had a dose and time-dependent response. MDP increased abscess formation only at high concentrations of Bacteroides fragilis, but clindamycin abolished this effect and reduced the number of abscesses to similar levels in both the clindamycin alone and clindamycin + MDP groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3762139&dopt=Abstract clindamycin antibiotic Cleocin-T



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Antipneumococcal activities of two novel macrolides, GW 773546 and GW 708408, compared with those of erythromycin, azithromycin, clarithromycin, clindamycin, and telithromycin.

Matic V, Kosowska K, Bozdogan B, Kelly LM, Smith K, Ednie LM, Lin G, Credito KL, Clark CL, McGhee P, Pankuch GA, Jacobs MR, Appelbaum PC.

Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033, USA.

The MICs of GW 773546, GW 708408, and telithromycin for 164 macrolide-susceptible and 161 macrolide-resistant pneumococci were low. The MICs of GW 773546, GW 708408, and telithromycin for macrolide-resistant strains were similar, irrespective of the resistance genotypes of the strains. Clindamycin was active against all macrolide-resistant strains except those with erm(B) and one strain with a 23S rRNA mutation. GW 773546, GW 708408, and telithromycin at two times their MICs were bactericidal after 24 h for 7 to 8 of 12 strains. Serial passages of 12 strains in the presence of sub-MICs yielded 54 mutants, 29 of which had changes in the L4 or L22 protein or the 23S rRNA sequence. Among the macrolide-susceptible strains, resistant mutants developed most rapidly after passage in the presence of clindamycin, GW 773546, erythromycin, azithromycin, and clarithromycin and slowest after passage in the presence of GW 708408 and telithromycin. Selection of strains for which MICs were >/=0.5 microg/ml from susceptible parents occurred only with erythromycin, azithromycin, clarithromycin, and clindamycin; 36 resistant clones from susceptible parent strains had changes in the sequences of the L4 or L22 protein or 23S rRNA. No mef(E) strains yielded resistant clones after passage in the presence of erythromycin and azithromycin. Selection with GW 773546, GW 708408, telithromycin, and clindamycin in two mef(E) strains did not raise the erythromycin, azithromycin, and clarithromycin MICs more than twofold. There were no change in the ribosomal protein (L4 or L22) or 23S rRNA sequences for 15 of 18 mutants selected for macrolide resistance; 3 mutants had changes in the L22-protein sequence. GW 773546, GW 708408, and telithromycin selected clones for which MICs were 0.03 to >2.0 microg/ml. Single-step studies showed mutation frequencies <5.0 x 10(-10) to 3.5 x 10(-7) for GW 773546, GW 708408, and telithromycin for macrolide-susceptible strains and 1.1 x 10(-7) to >4.3 x 10(-3) for resistant strains. The postantibiotic effects of GW 773546, GW 708408, and telithromycin were 2.4 to 9.8 h.

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Cleocin
On antibiotic prophylaxis in cardiac surgery: a risk factor for wound infection.

Lilienfeld DE, Vlahov D, Tenney JH, McLaughlin JS.

During a 30-month period, median sternotomy wound infections or endocarditis developed during the first 60 days postoperatively following 20 of 1,204 (1.7%) adult cardiac procedures at the University of Maryland Hospital. Fifty percent of the infected patients received perioperative clindamycin prophylaxis. A retrospective study was conducted in which the odds ratio estimate of the relative risk of sternotomy infection or endocarditis for patients receiving clindamycin prophylaxis compared with patients receiving cefamandole was found to be 17.0 (p less than .001) using population controls and 8.25 (p less than .001) using matched controls. Seventy-five percent of the organisms causing infections, principally Staphylococcus epidermidis, were resistant in vitro to clindamycin. Perioperative clindamycin administration was not fully effective in preventing wound infection following cardiac surgery at our hospital, thus providing indirect evidence for the efficacy of prophylaxis with cephalosporin-containing regimens. Trials of alternative antibiotics to clindamycin for prophylaxis in penicillin-allergic patients undergoing cardiac surgery are indicated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3789857&dopt=Abstract clindamycin antibiotic Cleocin-T



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An electron microscopic study of the effect of clindamycin therapy on bacterial adherence and glycocalyx formation in experimental Staphylococcus aureus osteomyelitis.

Mayberry-Carson KJ, Tober-Meyer B, Lambe DW Jr, Costerton JW.

After induction of experimental osteomyelitis with Staphylococcus aureus in a rabbit tibia model, clindamycin phosphate (280 mg/kg/day) was used to treat the infected animals for 1, 2 and 3 week periods. Scanning electron microscopy of samples of infected bone tissue taken at necropsy revealed masses of coccoid profiles embedded in a matrix of condensed exopolysaccharide material which adhered to the bone in both infected control animals and in infected animals treated for 1 week with clindamycin phosphate. After 2 and 3 weeks of clindamycin phosphate treatment, the infecting bacteria could not be cultured from tissue samples, and scanning electron microscopy of these samples revealed few coccoid profiles adhering to the bone and marrow. Radiological, microbiological, clinical, histological and electron microscopic findings all indicated recovery from the diseased state with increased length of clindamycin phosphate treatment.

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Clindamycin phosphate kinetics in subjects undergoing CAPD.

Schwartz MT, Kowalsky SF, McCormick EM, Parker MA, Echols RM.

The kinetics of intraperitoneally administered clindamycin phosphate were studied in 9 volunteer subjects undergoing CAPD. Volunteers were assigned to 2 groups with the first group receiving clindamycin phosphate 300 mg/l in exchanges 1 through 5, and the second group receiving clindamycin phosphate 300 mg/l in exchange 1, and then 30 mg/l in exchanges 2 through 5. Clindamycin serum and dialysate effluent levels were determined by bioassay. When admixed with dialysate fluid and instilled into the peritoneal cavity, clindamycin phosphate is rapidly activated. Serum concentrations of clindamycin were rapidly achieved in both groups during the first exchange. Subjects in groups I and II had peak serum levels of active drug within 3 (3.94 ug/ml) and 5 (7.35 ug/ml) h, respectively. These results support the practice of not only administering intraperitoneal clindamycin phosphate to treat CAPD-related peritonitis, but using this route of administration to treat systemic infections due to susceptible bacteria in patients without intravenous access.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3802597&dopt=Abstract clindamycin antibiotic Cleocin-T