April 29, 2017
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Flagyl Injection

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Flagyl Injection


Metronidazole is a synthetic antibacterial compound. Disposition of metronidazole in the body is similar for both oral and intravenous dosage forms, with an average elimination half-life in healthy humans of eight hours.

The major route of elimination of metronidazole and its metabolites is via the urine (60-80% of the dose), with fecal excretion accounting for 6-15% of the dose. The metabolites that appear in the urine result primarily from side-chain oxidation [1-(β-hydroxyethyl)-2-hydroxymethyl-5nitroimidazole and 2-methyl-5-nitroimidazole-1-yl-acetic acid] and glucuronide conjugation, with unchanged metronidazole accounting for approximately 20% of the total. Renal clearance of metronidazole is approximately 10 mL/min/1.73 m².

Metronidazole is the major component appearing in the plasma, with lesser quantities of the 2hydroxymethyl metabolite also being present. Less than 20% of the circulating metronidazole is bound to plasma proteins. Both the parent compound and the metabolite possess in vitro bactericidal activity against most strains of anaerobic bacteria.

Metronidazole appears in cerebrospinal fluid, saliva and breast milk in concentrations similar to those found in plasma. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.

Plasma concentrations of metronidazole are proportional to the administered dose. An eight-hour intravenous infusion of 100-4,000 mg of metronidazole in normal subjects showed a linear relationship between dose and peak plasma concentration.

In patients treated with intravenous metronidazole, using a dosage regimen of 15 mg/kg loading dose followed six hours later by 7.5 mg/kg every six hours, peak steady-state plasma concentrations of metronidazole averaged 25 mcg/mL with trough (minimum) concentrations averaging 18 mcg/mL.

Decreased renal function does not alter the single-dose pharmacokinetics of metronidazole. However, plasma clearance of metronidazole is decreased in patients with decreased liver function.

In one study newborn infants appeared to demonstrate diminished capacity to eliminate metronidazole. The elimination half-life, measured during the first three days of life, was inversely related to gestational age. In infants whose gestational ages were between 28 and 40 weeks, the corresponding elimination half-lives ranged from 109 to 22.5 hours.


Metronidazole is active in vitro against most obligate anaerobes, but does not appear to possess any clinically relevant activity against facultative anaerobes or obligate aerobes. Against susceptible organisms, metronidazole is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations. Metronidazole has been shown to have in vitro and clinical activity against the following organisms:

Anaerobic gram-negative bacilli, including

Bacteroides species, including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus)
Fusobacterium species

Anaerobic gram-positive bacilli, including

Clostridium species and susceptible strains of Eubacterium

Anaerobic gram-positive cocci, including

Peptococcus species
Peptostreptococcus species

Many nonspore-forming, gram-positive anaerobic rods are resistant to metronidazole1

Susceptibility Tests

Bacteriologic studies should be performed to determine the causative organisms and their susceptibility to metronidazole; however, the rapid, routine susceptibility testing of individual isolates of anaerobic bacteria is not always practical, and therapy may be started while awaiting these results.

Quantitative methods give the most accurate estimates of susceptibility to antibacterial drugs. A standardized agar dilution method and a broth microdilution method are recommended1. Interpretive criteria for determining the susceptibility of an organism to metronidazole are:

Dilution a
MIC (mcg/mL)
≤ 8 (S) Susceptible
16 (I) Intermediate
≥ 32 (R) Resistant
a MIC values for agar or broth microdilution are considered equivalent.

A bacterial isolate may be considered susceptible if the MIC value for metronidazole is not more than 8 mcg/mL. An organism with a metronidazole MIC of 16 mcg/mL is considered intermediate in susceptibility. An organism is considered resistant if the MIC is greater than 16 mcg/mL. The intermediate range was established because of the difficulty in reading endpoints and the clustering of MICs at or near breakpoint concentrations. Where data are available, the interpretive guidelines are based on pharmacokinetic data, population distributions of MICs, and studies of clinical efficacy. To achieve the best possible levels of a drug in abscesses and/or poorly perfused tissues, which are encountered commonly in these infections, maximum approved dosages of antimicrobial agents are recommended for therapy of anaerobic infections. When maximum dosages are used along with appropriate ancillary therapy, it is believed that organisms with susceptible endpoints are generally amenable to therapy, and those with intermediate endpoints may respond, but patient response should be carefully monitored. Ancillary therapy, such as drainage procedures and debridement, are of great importance for the proper management of anaerobic infections. A report of “resistant” from the laboratory indicates that the infecting organism is not likely to respond to therapy. Routine testing of metronidazole for management of C difficile-associated diarrhea is not recommended because correlation with clinical failures has not been established.1

Control strains are recommended for standardized susceptibility testing. Each time the test is performed, one or more control strains should be included. A clinical laboratory test is considered under acceptable control if the results of the control strains are within the MIC ranges reported below.2

For reference agar dilution testing, metronidazole MIC ranges associated with control strains are:

Control Strain ATCC® numbera MIC range (mcg/mL)
Bacteroides fragilis 25285 0.25 - 1
Bacteroides thetaiotaomicron 2974 0.5 - 2
Clostridium difficile 700057 0.125 – 0.5
a ATTC is a registered trademark of the American Type Culture Collection

For broth microdilution testing, metronidazole MIC ranges associated with control strains are:

Control Strain ATCC® numbera MIC range (mcg/mL)
Bacteroides fragilis 25285 0.25 - 2
Bacteroides thetaiotaomicron 2974 0.5 - 4
Eubacterium lentum 43055 0.125 – 0.5
a ATTC is a registered trademark of the American Type Culture Collection


1. Clinical and Laboratory Standards Institute. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard—Seventh Edition. CLSI document M11-A7. Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2007.

2. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Informational Supplement. CLSI document M11-S1 Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2009

Last reviewed on RxList: 12/15/2016
This monograph has been modified to include the generic and brand name in many instances.

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