Mechanism of Action:
As with other cephalosporins, bactericidal activity of cefdinir results from inhibition of cell wall synthesis. Cefdinir is stable in the presence of some, but not all, β-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins are susceptible to cefdinir.
Mechanism of Resistance:
Resistance to cefdinir is primarily through hydrolysis by some β-lactamases, alteration of penicillin-binding proteins (PBPs) and decreased permeability. Cefdinir is inactive against most strains of
Enterobacter spp.,
Pseudomonas spp.,
Enterococcus spp., penicillin-resistant streptococci, and methicillin-resistant staphylococci. β-lactamase negative, ampicillin-resistant (BLNAR)
H. influenzae strains are typically non-susceptible to cefdinir.
Antimicrobial Activity:
Cefdinir has been shown to be active against most strains of the following microorganisms, both
in vitro and in clinical infections as described in
INDICATIONS AND USAGE.
Gram-Positive Bacteria:
Staphylococcus aureus (methicillin-susceptible strains only)
Streptococcus pneumoniae (penicillin-susceptible strains only)
Streptococcus pyogenes
Gram-Negative Bacteria:
Haemophilus influenzae
Haemophilus parainfluenzae
Moraxella catarrhalis
The following
in vitro data are available, but their clinical significance is unknown.
Cefdinir exhibits
in vitro minimum inhibitory concentrations (MICs) of 1 mcg/mL or less against (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of cefdinir in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.
Gram-Positive Bacteria:
Staphylococcus epidermidis (methicillin-susceptible strains only)
Streptococcus agalactiae
Viridans group streptococci
Gram-Negative Bacteria:
Citrobacter koseri
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Susceptibility Test Methods:
When available, the clinical microbiology laboratory should provide periodic reports that describe the regional/local susceptibility profile of potential 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 method
1(broth and/or agar). The MIC values should be interpreted according to criteria provided in Table 1.
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 should be determined using a standardized method.
2The procedure uses paper disks impregnated with 5 mcg cefdinir to test the susceptibility of bacteria. The disk diffusion interpretive criteria are provided in Table 1.
Table 1: Susceptibility Test Interpretive Criteria for Cefdinir
| Minimum Inhibitory
| Zone Diameter
|
| Microorganisms
Streptococci other than S. pneumoniae that are susceptible to penicillin (MIC ≤ 0.12 mcg/mL), can be considered susceptible to cefdinir.
| Concentration (mcg/mL)
| (mm)
|
| S
| I
| R
| S
| I
| R
|
Haemophilus influenzae
| ≤ 1
| -
| -
| ≥ 20
| -
| --
|
Haemophilus parainfluenzae
| ≤ 1
| -
| -
| ≥ 20
| -
| --
|
Moraxella catarrhalis
| ≤ 1
| 2
| ≥ 4
| ≥ 20
| 17 to 19
| ≤ 16
|
| Streptococcus pneumoniae
S. pneumoniae that are susceptible to penicillin (MIC ≤ 0.06 mcg/mL) can be considered susceptible to cefdinir. Isolates of S. pneumoniae tested against a 1-μg oxacillin disk with oxacillin zone sizes ≥ 20 mm are susceptible to penicillin and can be considered susceptible to cefdinir. Testing of cefdinir against penicillin-intermediate or penicillin-resistant isolates is not recommended. Reliable interpretive criteria for cefdinir are not available.
| ≤ 0.5
| 1
| ≥ 2
| -
| -
| -
|
Susceptibility of staphylococci to cefdinir may be deduced from testing penicillin and either cefoxitin or oxacillin. Staphylococci susceptible to oxacillin (cefoxitin) can be considered susceptible to cefdinir.3
A report of "Susceptible" indicates that antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the site of infection necessary to inhibit growth of the pathogen. 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 pathogen if the antimicrobial compound reaches the concentrations 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 individual performing the test.
1,2,3 Standard cefdinir powder should provide the following range of MIC values as noted in Table 2. For the diffusion technique using a 5 mcg disk the criteria in Table 2 should be achieved.
Table 2: Acceptable Quality Control Ranges for Cefdinir
QC Strain
| Minimum Inhibitory Concentration (mcg/mL)
| Zone Diameter (mm)
|
Escherichia coli ATCC 25922
| 0.12 to 0.5
| 24 to 28
|
Haemophilus influenzae ATCC 49766
| 0.12 to 0.5
| 24 to 31
|
Staphylococcus aureus ATCC 25923
| -
| 25 to 32
|
Staphylococcus aureus ATCC 29213
| 0.12 to 0.5
| -
|
Streptococcus pneumoniae ATCC 49619
| 0.03 to 0.25
| 26 to 31
|
