Pharmacokinetics and Tissue Penetration of a Single 1,000-milligram, Intravenous Dose of Metronidazole for Antibiotic Prophylaxis of Colorectal Surgery

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1991 Dec 1

PMID 1810194

Citations 7

Authors

C Martin

B Sastre

M N Mallet

B Bruguerolle

J P Brun

P De Micco

F Gouin

Affiliations

Soon will be listed here.

Abstract

The levels of metronidazole in serum and tissue penetration of metronidazole were studied after prophylactic administration in 11 patients undergoing elective colorectal surgery. A single dose of 1,000 mg given intravenously was administered before surgery. Adequate drug levels in serum (greater than or equal to MIC for 90% of strains tested [MIC90] for Bacteroides fragilis) were found in all patients throughout the procedure. Mean peak (15-min) and last-determined (24-h) metronidazole levels in serum were 28.8 +/- 8 and 4.2 +/- 1.7 mg/liter, respectively. The beta-phase elimination half-life was 9.5 +/- 2.3 h, and the clearance and apparent volume of distribution were 57 +/- 13 ml/min and 0.7 +/- 0.1 liter/kg, respectively. In the colonic wall at surgical anastomosis, tissue metronidazole levels greater than or equal to MIC90 for B. fragilis were found in 91% of patients. In the abdominal wall fat and epiploic fat, tissue metronidazole levels greater than or equal to MIC90 for B. fragilis were found in 40 to 60% of patients at surgical incision and closure. No anaerobic infection occurred during the study.

Citing Articles

The mammalian clock and chronopharmacology.

Griffett K, Burris T Bioorg Med Chem Lett. 2013; 23(7):1929-34.

PMID: 23481644 PMC: 4864859. DOI: 10.1016/j.bmcl.2013.02.015.

Prospective observational study comparing three different treatment regimes in patients with Clostridium difficile infection.

Wenisch J, Schmid D, Kuo H, Allerberger F, Michl V, Tesik P Antimicrob Agents Chemother. 2012; 56(4):1974-8.

PMID: 22252830 PMC: 3318337. DOI: 10.1128/AAC.05647-11.

Pharmacokinetics and pharmacodynamics of intravenous levofloxacin at 750 milligrams and various doses of metronidazole in healthy adult subjects.

Sprandel K, Schriever C, Pendland S, Quinn J, Gotfried M, Hackett S Antimicrob Agents Chemother. 2004; 48(12):4597-605.

PMID: 15561831 PMC: 529226. DOI: 10.1128/AAC.48.12.4597-4605.2004.

Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials.

Lamp K, Freeman C, Klutman N, Lacy M Clin Pharmacokinet. 1999; 36(5):353-73.

PMID: 10384859 DOI: 10.2165/00003088-199936050-00004.

Comparison of concentrations of sulbactam-ampicillin administered by bolus injections or bolus plus continuous infusion in tissues of patients undergoing colorectal surgery.

Martin C, Cotin A, Giraud A, Alliot P, Mallet M, ARGEME M Antimicrob Agents Chemother. 1998; 42(5):1093-7.

PMID: 9593133 PMC: 105751. DOI: 10.1128/AAC.42.5.1093.

References

Zak O, KRADOLFER F . Effects of subminimal inhibitory concentrations of antibiotics in experimental infections. Rev Infect Dis. 1979; 1(5):862-79. DOI: 10.1093/clinids/1.5.862. View

Keighley M, Arabi Y, Alexander-Williams J, Youngs D, Burdon D . Comparison between systemic and oral antimicrobial prophylaxis in colorectal surgery. Lancet. 1979; 1(8122):894-7. DOI: 10.1016/s0140-6736(79)91373-4. View

Hunt P, FRANCIS J, Peck G, Farrell K, Sali A . Tinidazole in the prevention of wound infection after elective colorectal surgery. Med J Aust. 1979; 1(4):107-9. DOI: 10.5694/j.1326-5377.1979.tb112039.x. View

Brass C, Richards G, Ruedy J, Prentis J, HINCHEY E . The effect of metronidazole on the incidence of postoperative wound infection in elective colon surgery. Am J Surg. 1978; 135(1):91-6. DOI: 10.1016/0002-9610(78)90016-8. View

Pitt H, Roberts R, Johnson Jr W . Gentamicin levels in the human biliary tract. J Infect Dis. 1973; 127(3):299-302. DOI: 10.1093/infdis/127.3.299. View

Polk Jr H, LOPEZ-MAYOR J . Postoperative wound infection: a prospective study of determinant factors and prevention. Surgery. 1969; 66(1):97-103. View

Burke J . The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery. 1961; 50:161-8. View

Martin C, Bruguerolle B, Mallet M, Condomines M, Sastre B, Gouin F . Pharmacokinetics and tissue penetration of a single dose of ornidazole (1,000 milligrams intravenously) for antibiotic prophylaxis in colorectal surgery. Antimicrob Agents Chemother. 1990; 34(10):1921-4. PMC: 171965. DOI: 10.1128/AAC.34.10.1921. View

DiPiro J, Cheung R, Bowden Jr T, Mansberger J . Single dose systemic antibiotic prophylaxis of surgical wound infections. Am J Surg. 1986; 152(5):552-9. DOI: 10.1016/0002-9610(86)90228-x. View

10.

Bergamini T, Polk Jr H . The importance of tissue antibiotic activity in the prevention of operative wound infection. J Antimicrob Chemother. 1989; 23(3):301-13. DOI: 10.1093/jac/23.3.301. View

11.

Kaiser A . Antimicrobial prophylaxis in surgery. N Engl J Med. 1986; 315(18):1129-38. DOI: 10.1056/NEJM198610303151805. View

12.

Kling P, HOLMLUND D, Burman L . Single-dose intravenous metronidazole v. doxycycline prophylaxis in colorectal surgery. An open prospective, randomized trial. Acta Chir Scand. 1985; 151(2):163-8. View

13.

Tally F, Cuchural Jr G, Jacobus N, Gorbach S, Aldridge K, Cleary T . Nationwide study of the susceptibility of the Bacteroides fragilis group in the United States. Antimicrob Agents Chemother. 1985; 28(5):675-7. PMC: 176355. DOI: 10.1128/AAC.28.5.675. View

14.

LORIAN V . Low concentrations of antibiotics. J Antimicrob Chemother. 1985; 15 Suppl A:15-26. DOI: 10.1093/jac/15.suppl_a.15. View

15.

Kosmidis J, Stathakis C, Mantopoulos K, Pouriezi T, Papathanassiou B, Daikos G . Clinical pharmacology of cefotaxime including penetration into bile, sputum, bone and cerebrospinal fluid. J Antimicrob Chemother. 1980; 6 Suppl A:147-51. DOI: 10.1093/jac/6.suppl_a.147. View

16.

Mittermayer H, Gross C, Brucke P . Single dose cefuroxime/metronidazole versus metronidazole alone in elective colorectal surgery. Am Surg. 1984; 50(8):418-23. View

17.

Ralph E . Clinical pharmacokinetics of metronidazole. Clin Pharmacokinet. 1983; 8(1):43-62. DOI: 10.2165/00003088-198308010-00003. View

18.

Mitchell N, Evans D, Pollock D . Single dose metronidazole with and without cefuroxime in elective colorectal surgery. Br J Surg. 1983; 70(11):668-9. DOI: 10.1002/bjs.1800701109. View

19.

Mutch D, Richards G, BROWN R, Mulder D . Bioactive antibiotic levels in the human aorta. Surgery. 1982; 92(6):1068-71. View

20.

Baum M, Anish D, CHALMERS T, Sacks H, SMITH Jr H, Fagerstrom R . A survey of clinical trials of antibiotic prophylaxis in colon surgery: evidence against further use of no-treatment controls. N Engl J Med. 1981; 305(14):795-9. DOI: 10.1056/NEJM198110013051404. View