SUPRAX (Page 5 of 7)

12.4 Microbiology

Mechanism of Action

As with other cephalosporins, the bactericidal action of cefixime results from inhibition of cell wall synthesis. Cefixime is stable in the presence of certain beta-lactamase enzymes. As a result, certain organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases may be susceptible to cefixime.

Resistance

Resistance to cefixime in isolates of Haemophilus influenzae and Neisseria gonorrhoeae is most often associated with alterations in penicillin-binding proteins (PBPs). Cefixime may have limited activity against Enterobacteriaceae producing extended spectrum beta-lactamases (ESBLs). Pseudomonas species, Enterococcus species, strains of Group D streptococci, Listeria monocytogenes, most strains of staphylococci (including methicillin-resistant strains), most strains of Enterobacter species, most strains of Bacteroides fragilis, and most strains of Clostridium species are resistant to cefixime.

Antimicrobial Activity

Cefixime has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see INDICATIONS AND USAGE (1)}.

Gram-positive Bacteria

Streptococcus pneumoniae

Streptococcus pyogenes

Gram-negative Bacteria

Escherichia coli

Haemophilus influenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

Proteus mirabilis

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

Gram-positive Bacteria

Streptococcus agalactiae

Gram-negative Bacteria

Citrobacter amalonaticus

Citrobacter diversus

Haemophilus parainfluenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Pasteurella multocida

Proteus vulgaris

Providencia species

Salmonella species

Serratia marcescens

Shigella species

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas 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 for treatment.

Dilution techniques:

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,2 (broth and/or agar). The MIC values should be interpreted according to criteria provided in Table 3.

Diffusion techniques:

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.2.3 This procedure uses paper disks impregnated with 5 mcg cefixime to test the susceptibility of bacteria to cefixime. The disc diffusion breakpoints are provided in Table 3.

Table 3: Susceptibility Interpretive Criteria for Cefixime
*
Do not test Morganella species by disk diffusion
Test Haemophilus influenzae using Haemophilus Test Medium (HTM)
The current absence of resistant isolates precludes defining any results other than “susceptible” Isolates yielding results other than susceptible should be subjected to additional testing.
§
Test Neisseria gonorrhoeae using GC agar base and 1% defined growth supplement. Minimum inhibitory concentrations are determined using the agar dilution method.
Pathogen Minimum Inhibitory Concentrations ( mcg / mL ) Disk Diffusion Zone Diameter ( mm )
S I R S I R
Enterobacteriaceae * ≤ 1 2 ≥ 4 ≥ 19 16 to 18 ≤ 15
Haemophilus influenzae . ≤1 NA NA ≥21 NA NA
Neisseria gonorrhoeae , § ≤ 0.25 NA NA ≥ 31 NA NA

A report of Susceptible (S) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate (I) 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 the 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 (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the infection site; 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 individuals performing the test.1,2,3 Standard cefixime powder should provide the following range of MIC values noted in Table 4. For the diffusion technique using the 5 mcg disk, the criteria in Table 4 should be achieved.

Table 4: Acceptable Quality Control Ranges for Cefixime

ATCC = American Type Culture Collection

Quality Control Organisms Minimum Inhibitory Concentrations ( mcg / mL ) Disk Diffusion Zone Diameter ( mm )
E . coli ATCC 25922 0.25 to 1 23 to 27
H . influenzae ATCC 49247 0.12 to 1 25 to 33
N . gonorrhoeae ATCC 49226 0.004 to 0.03 37 to 45
S . pneumoniae ATCC 49619 NA 16 to 23
S . aureus ATCC 29213 8 to 32 NA

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