Antibiotic control policies can be developed to ensure quality care and can be designed to select for cost-effective agents. Prospective and continuous monitoring of antibiotic usage by the IDS resulted in a significant and sustained reduction in antibiotic costs without detrimental effect on the length of therapy or deaths.

The comparative pharmacokinetics and serum inhibitory effects of clindamycin were evaluated in six healthy male subjects given multiple-dose infusions of the following regimens in a crossover fashion: 600 mg every 6 h, 900 mg every 8 h, and 1,200 mg every 12 h. Serial blood samples were obtained after the last dose in each regimen and analyzed for clindamycin by a sensitive and specific high-performance liquid chromatography assay technique. Clindamycin pharmacokinetics were estimated by using noncompartmental methods, and serum inhibitory titers were serially determined against Bacteroides fragilis ATCC 25285 and evaluated by using area under the serum inhibitory curve (AUIC). Maximum and minimum concentrations in plasma averaged 12.2 + 1.6 and 1.2 + 0.6, 16.3 + 4.0 and 0.9 ± 0.5, and 16.8 ± 2.5 and 0.4 ± 0.2 ,ug/ml for the 600-, 900-, and 1,200-mg regimens, respectively. Clindamycin plasma clearance and elimination half-life averaged 23.3 ± 4.0 liters/h and 1.9 ± 0.4 h for the 600-mg regimen, 25.6 ± 8.2 liters/h and 2.1 ± 0.4 h for the 900-mg regimen, and 26.4 ± 4.7 liters/h and 2.1 ± 0.4 h for the 1,200-mg regimen. These results were not significantly different. Apparent volume of distribution increased significantly for the 1,200-mg regimen compared with the 600-mg regimen. Mean maximum reciprocal serum inhibitory titers were 96 ± 35, 101 ± 43, and 160 ± 78 for the 600-, 900-, and 1,200-mg regimens, respectively. Minimum reciprocal serum inhibitory titers averaged 12 ± 4, 6 ± 3, and 5 ± 2 for the low-, medium-, and high-dose regimens, respectively. Mean AUIC increased roughly in proportion to dose. Similar daily values for the area under the concentration-time curve and for AUIC for each of the regimens suggest similar daily drug exposure and serum inhibitory activity. A regimen of 1,200 mg every 12 h may represent an alternative dosing strategy for clindamycin.Clindamycin remains a frequently prescribed agent for the treatment of serious anaerobic and mixed aerobic-anaerobic infections, especially those involving Bacteroidesfragilis (3, 4). The combination of clindamycin and an aminoglycoside is regarded by many as the standard therapy for mixed aerobic-anaerobic infections, particularly those within the pelvic and abdominal cavities (9). Recent attention has focused on more cost-effective ways to administer parenteral clindamycin, such as administration of 900 mg every 8 h together with an aminoglycoside in the same admixture (1, 10). Despite prolonged clinical use of this drug, uncertainty remains as to the optimum way in which to administer clindamycin in various settings.Relatively little is known regarding the pharmacokinetics of intravenous clindamycin administered as clindamycin phosphate. Results from earlier studies are limited because of microbiological assay techniques which are not able to differentiate between clindamycin and active metabolites (5, 11). We have developed a sensitive and specific high-performance liquid chromatographic assay for clindamycin (G. La Follette, J. Gambertoglio, J. A...

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The pharmacokinetic disposition of cefotaxime, desacetyl cefotaxime, and mezlocillin after the administration of each drug singly and in combination was examined in eight healthy volunteers and in five anuric patients with end-stage renal disease (ESRD). In the presence of ESRD, the total body clearance of cefotaxime decreased from 256.7 +/- 41.5 to 65.4 +/- 42.0 ml/min, and its elimination half-life (t1/2) increased from 1.1 to 3.6 hours as compared with healthy volunteers. Concomitant administration of mezlocillin in healthy volunteers decreased the total body clearance of cefotaxime by 42% and increased its steady-state volume of distribution. This reduction in clearance was reflected by a decrease in both renal and nonrenal clearances. In the presence of ESRD, coadministration of mezlocillin increased the t1/2 of cefotaxime to 5.8 hours. Desacetyl cefotaxime accumulated in ESRD with a prolongation of its elimination t1/2 to 18.7 hours from 1.7 hours in healthy volunteers. Desacetyl cefotaxime peak plasma concentrations occurred later with the combination regimen in the presence of ESRD. The clearance of mezlocillin was reduced and t1/2 prolonged in ESRD from 194.6 +/- 31.9 to 76.4 +/- 38.8 ml/min and 1.4 to 2.3 hours, respectively. Concomitant administration of cefotaxime did not alter the pharmacokinetics of mezlocillin. These data suggest that in the presence of normal renal function, lower doses of cefotaxime may be adequate to maintain similar cefotaxime plasma concentrations when mezlocillin is coadministered compared to when cefotaxime is given alone. Additional pharmacodynamic and clinical studies with this combination are warranted to further elucidate the clinical impact of this pharmacokinetic interaction.

In evaluating antimicrobial agents with similar spectra of activity, it is difficult to determine equivalent dosage regimens. In vitro potency, pharmacokinetic disposition, and other factors determine the usual dosing regimen. Knowledge of the serum bactericidal activity over time may assist in defining the potency of comparative antimicrobial agents. Cefoxitin and ceftizoxime, cephalosporins with gram-negative aerobic and anaerobic activity, have been promoted as monotherapy in the treatment of intra-abdominal infection. In a randomized, crossover study, six healthy volunteers received single 30-mg/kg doses of cefoxitin and ceftizoxime. Greater serum activity against Escherichia coli and Bacteroides fragilis was observed with ceftizoxime than with cefoxitin. The results suggest that ceftizoxime can be administered in a lower daily dosage than cefoxitin. We propose that the present study may serve as a prototype for future studies attempting to assess equivalent dosing regimens for antibiotics with similar spectra of activity.A variety of antimicrobial agents have been used as monotherapy in the treatment of mixed aerobic-anaerobic intra-abdominal infection. Cephalosporins such as cefoxitin (4), cefotetan (2), and certain broad-spectrum agents such as ceftizoxime (6) and cefotaxime (10) have been found to have a role in this setting. Which agent is best suited for the treatment of intra-abdominal infection is unclear. Considering the similarity of these antibiotics with respect to their antimicrobial spectrum and toxicity, the choice of antibiotic is often based on cost factors. When comparing like antimicrobial agents, it is difficult to determine the equivalence of dosing regimens. Knowledge of the serum bactericidal activity over time may result in a useful method of determining dosage equivalence.The most common pathogens associated with intra-abdominal sepsis are Bacteroides fragilis and Escherichia coli (11). Cefoxitin and ceftizoxime have similar activity against B. fragilis, with reported MICs for 90% of strains tested (MIC90s) of 16 to 32 ,ug/ml (3, 5, 8). Against E. coli, the MIC90 of cefoxitin has been reported to be 2 to 6 ,ug/ml, whereas the MIC90 of ceftizoxime ranges from 0.06 to 0.25 ,ug/ml (3, 5, 8).A potential limitation of the use of cefoxitin is its short half-life (0.8 h), necessitating frequent doses in the treatment of infection (9). Ceftizoxime, with a longer half-life (1.6 h) (8) and increased potency versus gram-negative aerobes, may offer certain advantages over cefoxitin, resulting in the need for lower doses or less frequent administration.We elected to study the serum bactericidal activity over time of cefoxitin and ceftizoxime.