Cephalexin is the oral first generation agent widely used in the USA. After oral doses of 500 mg, peak serum levels are 15–20 mcg/mL. Urine concentration is usually very high, but in most tissues levels are variable and generally lower than in serum. Cephalexin is typically given in oral dosages of 0.25–0.5 g four times daily (15–30 mg/kg/d). Excretion is mainly by glomerular filtration and tubular secretion into the urine. Drugs that block tubular secretion, eg, probenecid, may increase serum levels substantially. In patients with impaired renal function, dosage must be reduced (Table 43–2).
FIGURE 43–6 Structures of some cephalosporins. R1 and R2 structures are substituents on the 7-aminocephalosporanic acid nucleus pictured at the top. Other structures (cefoxitin and below) are complete in themselves. 1Additional substituents not shown.
TABLE 43–2 Guidelines for dosing of some commonly used cephalosporins and other cell-wall inhibitor antibiotics.
1The total dose should not exceed the adult dose.
2The dose shown is during the first week of life. The daily dose should be increased by approximately 33–50% after the first week of life. The lower dosage range should be used for neonates weighing less than 2 kg. After the first month of life, pediatric doses may be used. 350% of dose for Clcr <30 mL/min.
B. Parenteral
Cefazolin is the only first-generation parenteral cephalosporin still in general use. After an intravenous infusion of 1 g, the peak level of cefazolin is approximately 185 mcg/mL. The usual intravenous dosage of cefazolin for adults is 0.5–2 g intravenously every 8 hours. Cefazolin can also be administered intramuscularly. Excretion is via the kidney, and dose adjustments must be made for impaired renal function.
Oral drugs may be used for the treatment of urinary tract infections and staphylococcal or streptococcal infections, including cellulitis or soft tissue abscess. However, oral cephalosporins should not be relied on in serious systemic infections.
Cefazolin penetrates well into most tissues. It is a drug of choice for surgical prophylaxis and for many streptococcal and staphylococcal infections requiring intravenous therapy. Cefazolin may be used for infections due to E coli or K pneumoniae when the organism has been documented to be susceptible. Cefazolin does not penetrate the central nervous system and cannot be used to treat meningitis. Cefazolin is better tolerated than antistaphylococcal penicillins, and it has been shown to be effective for serious staphylococcal infections, eg, bacteremia. It can also be used in patients with mild penicillin allergy other than immediate hypersensitivity.