Cefdinir (Page 2 of 8)

Special Populations

Patients with Renal Insufficiency

Cefdinir pharmacokinetics were investigated in 21 adult subjects with varying degrees of renal function. Decreases in cefdinir elimination rate, apparent oral clearance (CL/F), and renal clearance were approximately proportional to the reduction in creatinine clearance (CL cr ). As a result, plasma cefdinir concentrations were higher and persisted longer in subjects with renal impairment than in those without renal impairment. In subjects with CL cr between 30 and 60 mL/min, C max and t ½ increased by approximately 2-fold and AUC by approximately 3-fold. In subjects with CL cr <30 mL/min, C max increased by approximately 2-fold, t ½ by approximately 5-fold, and AUC by approximately 6-fold. Dosage adjustment is recommended in patients with markedly compromised renal function (creatinine clearance <30 mL/min; see DOSAGE AND ADMINISTRATION).

Hemodialysis

Cefdinir pharmacokinetics were studied in 8 adult subjects undergoing hemodialysis. Dialysis (4 hours duration) removed 63% of cefdinir from the body and reduced apparent elimination t ½ from 16 (±3.5) to 3.2 (±1.2) hours. Dosage adjustment is recommended in this patient population (see DOSAGE AND ADMINISTRATION).

Hepatic Disease

Because cefdinir is predominantly renally eliminated and not appreciably metabolized, studies in patients with hepatic impairment were not conducted. It is not expected that dosage adjustment will be required in this population.

Geriatric Patients

The effect of age on cefdinir pharmacokinetics after a single 300 mg dose was evaluated in 32 subjects 19 to 91 years of age. Systemic exposure to cefdinir was substantially increased in older subjects (N=16), C max by 44% and AUC by 86%. This increase was due to a reduction in cefdinir clearance. The apparent volume of distribution was also reduced, thus no appreciable alterations in apparent elimination t ½ were observed (elderly: 2.2 ± 0.6 hours vs young: 1.8 ± 0.4 hours). Since cefdinir clearance has been shown to be primarily related to changes in renal function rather than age, elderly patients do not require dosage adjustment unless they have markedly compromised renal function (creatinine clearance <30 mL/min, see Patients with Renal Insufficiency, above).

Gender and Race

The results of a meta-analysis of clinical pharmacokinetics (N=217) indicated no significant impact of either gender or race on cefdinir pharmacokinetics.

Microbiology

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. 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.

Aerobic Gram-Positive Microorganisms

Staphylococcus aureus (including β-lactamase producing strains)
NOTE: Cefdinir is inactive against methicillin-resistant staphylococci.
Streptococcus pneumoniae (penicillin-susceptible strains only) Streptococcus pyogenes

Aerobic Gram-Negative Microorganisms

Haemophilus influenzae (including β-lactamase producing strains)
Haemophilus parainfluenzae (including β-lactamase producing strains)
Moraxella catarrhalis (including β-lactamase producing strains)
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.

Aerobic Gram-Positive Microorganisms

Staphylococcus epidermidis (methicillin-susceptible strains only)
Streptococcus agalactiae
Viridans group streptococci NOTE: Cefdinir is inactive against Enterococcus and methicillin-resistant Staphylococcus species.

Aerobic Gram-Negative Microorganisms

Citrobacter diversus
Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis NOTE: Cefdinir is inactive against Pseudomonas and Enterobacter species.

Susceptibility Tests

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 procedure. Standardized procedures are based on a dilution method (1) (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of cefdinir powder. The MIC values should be interpreted according to the following criteria: For organisms other than Haemophilus spp. and Streptococcus spp:

MIC (mcg/mL) Interpretation
≤1 Susceptible (S)
2 Intermediate (I)
≥4 Resistant (R)

For Haemophilus spp: a

MIC (mcg/mL) Interpretation b
a These interpretive standards are applicable only to broth microdilution susceptibility tests with Haemophilus spp. using Haemophilus Test Medium (HTM). (1) b The current absence of data on resistant strains precludes defining any results other than “Susceptible.” Strains yielding MIC results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.
≤1 Susceptible (S)

For Streptococcus spp:
Streptococcus pneumoniae that are susceptible to penicillin (MIC ≤0.06 mcg/mL), or streptococci other than S. pneumoniae that are susceptible to penicillin (MIC≤0.12 mcg /mL), 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.
A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable. 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 high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected. Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of laboratory procedures. Standard cefdinir powder should provide the following MIC values:

Microorganism MIC Range (mcg/mL)
c This quality control range is applicable only to H. influenzae ATCC 49766 tested by a broth microdilution procedure using HTM.
Escherichia coli ATCC 25922 0.12-0.5
Haemophilus influenzae ATCC 49766 c 0.12-0.5
Staphylococcus aureus ATCC 29213 0.12-0.5

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