Cephalexin

CEPHALEXIN- cephalexin capsule
Medsource Pharmaceuticals

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin and other antibacterial drugs, cephalexin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Human Pharmacology

Cephalexin is acid stable and may be given without regard to meals. It is rapidly absorbed after oral administration. Following doses of 250 mg, 500 mg, and 1 g, average peak serum levels of approximately 9, 18, and 32 mcg/mL respectively were obtained at 1 hour. Measurable levels were present 6 hours after administration. Cephalexin is excreted in the urine by glomerular filtration and tubular secretion. Studies showed that over 90% of the drug was excreted unchanged in the urine within 8 hours. During this period, peak urine concentrations following the 250 mg, 500 mg, and l g doses were approximately 1000, 2200, and 5000 mcg/mL respectively.

Microbiology

In vitro tests demonstrate that the cephalosporins are bactericidal because of their inhibition of cell-wall synthesis. Cephalexin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Aerobes, Gram-positive
Staphylococcus aureus (including penicillinase-producing strains)
Streptococcus pneumoniae (penicillin-susceptible strains)
Streptococcus pyogenes
Aerobes, Gram-negative
Escherichia coli
Haemophilus influenzae
Klebsiella pneumoniae
Moraxella (Branhamella) catarrhalis
Proteus mirabilis
Note — Methicillin-resistant staphylococci and most strains of enterococci ( Enterococcus faecalis [formerly Streptococcus faecalis ]) are resistant to cephalosporins, including cephalexin. It is not active against most strains of Enterobacter spp., Morganella morganii , and Proteus vulgaris. It has no activity against Pseudomonas spp. or Acinetobacter calcoaceticus. Penicillin-resistant Streptococcus pneumoniae is usually cross-resistant to beta-lactam antibiotics.
Susceptibility Tests
Dilution techniques — Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC’s). These MIC’s provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC’s should be determined using a standardized procedure. Standardized procedures are based on a dilution method ^{1 to 3} (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of cephalothin powder. The MIC values should be interpreted according to the following criteria:

MIC (mcg/mL)	Interpretation
≤8	Susceptible (S)
16	Intermediate (I)
≥32	Resistant (R)

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations 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 the laboratory procedures. Standard cephalothin powder should provide the following MIC values:

Microorganism	MIC (mcg/mL)
E. coli ATCC 25922	4-16
S. aureus ATCC 29213	0.12-0.5

Diffusion techniques — Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure ^2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg cephalothin to test the susceptibility of microorganisms to cephalexin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 mcg cephalothin disk should be interpreted according to the following criteria:

Zone Diameter (mm)	Interpretation
≥18	Susceptible (S)
15-17	Intermediate (I)
≤14	Resistant (R)

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cephalexin. As with standard dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 mcg cephalothin disk should provide the following zone diameters in these laboratory test quality control strains:

Microorganism	Zone Diameter (mm)
E. coli ATCC 25922	15-21
S. aureus ATCC 25923	29-37

INDICATIONS AND USAGE

Cephalexin capsules are indicated for the treatment of the following infections when caused by susceptible strains of the designated microorganisms:
Respiratory tract infections caused by Streptococcus pneumoniae and Streptococcus pyogenes (Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cephalexin capsules are generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cephalexin capsules in the subsequent prevention of rheumatic fever are not available at present.)
Otitis media due to Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus, Streptococcus pyogenes , and Moraxella catarrhalis
Skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes
Bone infections caused by Staphylococcus aureus and/or Proteus mirabilis
Genitourinary tract infections, including acute prostatitis, caused by Escherichia coli , Proteus mirabilis, and Klebsiella pneumoniae
Note — Culture and susceptibility tests should be initiated prior to and during therapy. Renal function studies should be performed when indicated. To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin and other antibacterial drugs, cephalexin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.