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CLINICAL PHARMACOLOGY

After intramuscular (IM) injection of a 750-mg dose of cefuroxime to normal volunteers, the mean peak serum concentration was 27 mcg/mL. The peak occurred at approximately 45 minutes (range, 15 to 60 minutes). Following IV doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following IV administration of 1.5-g doses every 8 hours to normal volunteers. The serum half-life after either IM or IV injections is approximately 80 minutes.

Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations.

Following the IM administration of a 750-mg single dose, urinary concentrations averaged 1,300 mcg/mL during the first 8 hours. Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8-hour period.

The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cefuroxime is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.

Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of cefuroxime achieved in cerebrospinal fluid during multiple dosing of patients with meningitis.

Table 1: Concentrations of Cefuroxime Achieved in Cerebrospinal Fluid During Multiple Dosing of Patients with Meningitis

Patients Dose Number of Patients Mean (Range) CSF Cefuroxime Concentrations (mcg/mL) Achieved Within 8 Hours Post Dose
Pediatric patients (4 weeks to 6.5 years) 200 mg/kg/day, divided q 6 hours 5 6.6 (0.9-17.3)
Pediatric patients (7 months to 9 years) 200 to 230 mg/kg/day, divided q 8 hours 6 8.3 ( < 2-22.5)
Adults 1.5 grams q 8 hours 2 5.2 (2.7-8.9)
Adults 1.5 grams q 6 hours 10 6.0 (1.5-13.5)

Cefuroxime is approximately 50% bound to serum protein.

Microbiology

Mechanism of Action

Cefuroxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefuroxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Mechanism of Resistance

Resistance to cefuroxime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.

Interaction with Other Antimicrobials

In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and cefuroxime.

Cefuroxime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Gram-negative Bacteria
  • Enterobacter spp.
  • Escherichia coli
  • Klebsiella spp.
  • Haemophilus influenzae
  • Neisseria meningitidis
  • Neisseria gonorrhoeae
Gram-positive Bacteria
  • Staphylococcus aureus
  • Streptococcus pneumoniae
  • Streptococcus pyogenes

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefuroxime. However, the efficacy of cefuroxime in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Gram-negative Bacteria
  • Citrobacter spp.
  • Providencia rettgeri
  • Haemophilus parainfluenzae
  • Proteus mirabilis
  • Moraxella catarrhalis
  • Morganella morganii
  • Salmonella spp.
  • Shigella spp.
Gram-positive Bacteria
  • Staphylococcus epidermidis

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth or agar)1,2. The MIC values should be interpreted according to criteria provided in Table 2.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method2,3. This procedure uses paper disks impregnated with 30 mcg cefuroxime to test the susceptibility of microorganisms to cefuroxime. The disk diffusion interpretive criteria are provided in Table 2.

Table 2: Susceptibility Test Interpretive Criteria for Cefuroxime

Pathogen Minimum Inhibitory Concentrations (mcg/ml) Disk Diffusion Zone Diameters (mm)
(S) Susceptible (I) Intermediate (R) Resistant (S) Susceptible (I) Intermediate (R) Resistant
Haemophilus influenzae ≤ 4 8 ≥ 16 ≥ 20 17-19 ≤ 16
Enterobacteriaceae* ≤ 8 - ≥ 16 ≥ 18 - ≤ 17
Neisseria gonorrhoeae ≤ 1 2 ≥ 4 ≥ 31 26-30 ≤ 25
Streptococcus pneumoniae ≤ 0.5 1 ≥ 2 - - -
* For Enterobacteriaceae, susceptibility interpretive criteria are based on a dose of 1.5 g every 8 hours in patients with normal renal function.
Susceptibility of staphylococci to cefuroxime may be deduced from testing only penicillin and either cefoxitin or oxacillin.

A report of “Susceptible” indicates that the antimicrobial drug is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of “ Intermediate” indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test1,2,3. Standard cefuroxime powder should provide the following range of MIC values noted in Table 3. For the diffusion technique using the 30 mcg disk, the criteria in Table 3 should be achieved.

Table 3: Acceptable Quality Control Ranges for Cefuroxime

QC Strain Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion Zone diameters (mm)
Escherichia coli ATCC 25922 2 - 8 20 - 26
Staphylococcus aureus ATCC 25923 - 27 - 35
Staphylococcus aureus ATCC 29213 0.5 - 2 -
Streptococcus pneumoniae ATCC 49619 0.25-1  
Haemophilus influenzae ATCC 49766 0.25-1 28-36
Neisseria gonorrhoeae ATCC 49226 0.25 - 1 33 - 41

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.

2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fourth Informational Supplement, CLSI document M100-S24. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2014.

3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Eleventh Edition CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.

Last reviewed on RxList: 10/27/2014
This monograph has been modified to include the generic and brand name in many instances.

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