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Relative antibacterial efficacy of clindamycin and metronidazole against Bacteroides fragilis in vitro and in experimentally infected mice.

Dijkmans BA, Vaishnav J, Mattie H.

The antibacterial activity of clindamycin and metronidazole against Bacteroides fragilis was quantitated in vitro by MIC determination and colony counting at 24 h and in vivo from the effects on an experimental B. fragilis infection in mice; this infection was established after co-inoculation of B. fragilis and Escherichia coli. In vitro, clindamycin was 8 to 16 times more effective than metronidazole in terms of MIC values, and more than 30 times according to colony counts at 24 h. In vivo clindamycin was almost 8 times less effective than metronidazole according to dose. This was partly due to its less favorable pharmacokinetic properties, but clindamycin was still only 1.6 times more effective than metronidazole according to free plasma concentrations. In vivo neither clindamycin nor metronidazole had any antibacterial effect against E. coli. The discrepancy between the in vivo and in vitro results for B. fragilis is discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4028873&dopt=Abstract clindamycin antibiotic Cleocin-T



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Homology between clindamycin resistance plasmids in Bacteroides.

Guiney DG Jr, Hasegawa P, Davis CE.

Two different species of clindamycin-resistant Bacteroides were isolated from the same infection. One isolate contained a single 15-kb plasmid (pCP1) which encoded transferable clindamycin resistance. pCP1 appears similar to the Bacteroides clindamycin resistance plasmid pBFTM10 isolated independently by F.P. Tally, D.R. Snydman, M.J. Shimell, and M.H. Malamy (1982, J. Bacteriol. 151, 686-691). The second strain had a 10-kb plasmid (pCP2) but did not transfer resistance. DNA hybridization studies revealed that pCP1 shares a 5-kb region of homology with the B. fragilis R plasmid pBF4 studied by R.A. Welch and F.L. Macrina (1981, J. Bacteriol. 145, 867-872). This region in both plasmids was shown to be bounded by homologous direct repeats and contains the putative clindamycin resistance determinant. pCP1 and pCP2 were found to share extensive homology but sequences homologous to the clindamycin resistance region were missing from pCP2 and found instead in the whole cell DNA of the host strain. These results identify a transposon-like structure on Bacteroides clindamycin resistance plasmids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6087395&dopt=Abstract clindamycin antibiotic Cleocin-T



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Synergism between penicillin, clindamycin, or metronidazole and gentamicin against species of the Bacteroides melaninogenicus and Bacteroides fragilis groups.

Brook I, Coolbaugh JC, Walker RI, Weiss E.

Clinical isolates of the Bacteroides melaninogenicus and Bacteroides fragilis groups were tested for in vitro and in vivo susceptibility to penicillin, clindamycin, and metronidazole, used singly or in combination with gentamicin. The in vitro tests consisted of determinations of minimal inhibitory concentrations (MICs) carried out with or without constant amounts of gentamicin. When used alone, gentamicin had negligible effects on the bacteria but significantly reduced the MICs of penicillin, clindamycin, and metronidazole against 11, 10, and 3, of the 15 strains of the B. melaninogenicus group, respectively. The 15 strains of the B. fragilis group were all beta-lactamase producers and were highly resistant to penicillin or the combination of penicillin and gentamicin. However, gentamicin reduced the MICs of clindamycin and metronidazole against 1 and 7 strains of this group, respectively. The in vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the sizes and bacterial content of abscesses induced by subcutaneous injection of bacterial suspensions. The results of the in vivo tests were generally consistent with those obtained in vitro with strains of the B. melaninogenicus group. Synergism between gentamicin and penicillin, clindamycin, or metronidazole was shown in 13, 10, and 3 strains of this group, respectively. In vivo synergism was not clearly demonstrated with the strains of the B. fragilis group, possibly because clindamycin and metronidazole used alone were highly efficacious. We suggest that the synergistic effect of gentamicin is due to its increased transport into the bacterial cell in the presence of penicillin and, possibly, other antimicrobial agents. The newly recognized in vitro and in vivo synergism between penicillin and other antimicrobial agents and an aminoglycoside in B. melaninogenicus may have clinical implications that deserve to be investigated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6142680&dopt=Abstract clindamycin antibiotic Cleocin-T



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Clindamycin phosphate used in combination with tretinoin in the treatment of acne.

Rietschel RL, Duncan SH.

Sixty-four patients with acne were studied to evaluate the irritancy, tolerance, and systemic absorption of topical 1% clindamycin phosphate when combined with tretinoin gel 0.025% as compared to either agent alone. All these treatment regimens were effective and well-tolerated. Clindamycin alone was less irritating than tretinoin alone or tretinoin combined with clindamycin. The combination treatment produced fewer complaints from patients than tretinoin alone. No systemic absorption of clindamycin was detected after two weeks and eight weeks of usage.

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Comparative effects of clindamycin and lincomycin on end-plate currents and quantal content at the neuromuscular junction.

Fiekers JF, Henderson F, Marshall IG, Parsons RL.

The pre- and postjunctional effects of the lincosamide antibiotics, clindamycin and lincomycin, were studied in voltage-clamped transected twitch fibers of costocutaneous muscles of garter snakes (species Thamnophis). Miniature end-plate currents and end-plate currents (EPCs) were recorded over a wide voltage range for each antibiotic. The amplitude and kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined. High concentrations of clindamycin (2 X 10(-4) M) and lincomycin (2 X 10(-3) M) produced significant depression of EPC amplitude and a nonlinearity in the EPC-voltage relationships. The time constant of EPC decay was accelerated in clindamycin and the relationship between the time constant of EPC decay and membrane potential remained a single exponential function with a concentration-dependent loss of the voltage dependence. In contrast to clindamycin, lincomycin produced biphasic EPCs which consisted of two components, one faster and one slower than the control decay rate. The relative amplitude and decay rate of each component was both concentration and voltage dependent. Either increasing the concentration of lincomycin or membrane hyperpolarization decreased the amplitude ratio, iota slow/iota fast, and increased the ratio of the respective time constants, tau slow/tau fast. Clindamycin affected EPC decay amplitude and quantal content in the same concentration range, whereas lincomycin affected EPC decay at concentrations 20 times less than those required to reduce EPC amplitude and quantal content. These results suggest that the neuromuscular blocking effects of clindamycin involve both pre-and postjunctional sites, whereas the effects of lincomycin are primarily on the postjunctional receptor-channel complex.

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

Klempner MS, Styrt B.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6315671&dopt=Abstract clindamycin antibiotic Cleocin-T