CEPHALOSPORINS First used clinically in the early 1960’s. First used clinically in the early 1960’s. They have an important role in the modern treatment of bacterial infections. They have an important role in the modern treatment of bacterial infections. A wide variety of cephalosporins have become available. A wide variety of cephalosporins have become available.

CEPHALOSPORINS Semisynthetic antimicrobial agents closely related to the penicillins. Semisynthetic antimicrobial agents closely related to the penicillins. Commercially available cephalosporins contain the 7-amino cephalosporanic acid nucleus. Commercially available cephalosporins contain the 7-amino cephalosporanic acid nucleus.

CLASSIFICATION BY GENERATION First Generation Cephalosporins. First Generation Cephalosporins. Second Generation Cephalosporins. Second Generation Cephalosporins. Third Generation Cephalosporins. Third Generation Cephalosporins. Fourth Generation Cephalosporins. Fourth Generation Cephalosporins.

FIRST GENERATION - (CEFAZOLIN) Very active vs gram positive cocci. Very active vs gram positive cocci. Moderate activity against gram negative bacteria. Moderate activity against gram negative bacteria.

PHARMACOKINETICS Do not penetrate the CNS. Do not penetrate the CNS. Excretion is via the kidney and dose adjustments must be made for impaired renal function. Excretion is via the kidney and dose adjustments must be made for impaired renal function.

THERAPEUTIC USES Parenteral agents are used primarily for prophylaxis in various surgical procedures. Parenteral agents are used primarily for prophylaxis in various surgical procedures. Oral drugs used for minor staph infections or some polymicrobial infections. Oral drugs used for minor staph infections or some polymicrobial infections.

THERAPEUTIC USES Occasionally for gram negative infections. Occasionally for gram negative infections.

SECOND GENERATION- (CEFOXITIN) Extended gram negative coverage (less active vs gram positive organisms). Extended gram negative coverage (less active vs gram positive organisms).

PHARMACOKINETICS Several orally and parenterally available (cefoxitin-IV). Several orally and parenterally available (cefoxitin-IV). Poor penetration into the CNS. Poor penetration into the CNS. Dosage adjustments must be made in renal failure. Dosage adjustments must be made in renal failure.

THERAPEUTIC USES Variety of gram negative infections. Variety of gram negative infections.

THIRD GENERATION – Ceftriaxone and ceftazidime Expanded gram-negative coverage. Expanded gram-negative coverage. Cefoperazone and ceftazidime have excellent activity vs Pseudomonas. Cefoperazone and ceftazidime have excellent activity vs Pseudomonas.

PHARMACOKINETICS Cross the blood brain barrier well. Cross the blood brain barrier well. Half-lives and the necessary dosing intervals vary greatly (ceftriaxone once every 24h). Half-lives and the necessary dosing intervals vary greatly (ceftriaxone once every 24h). Most are excreted by the kidney and require dosage adjustment (cefoperazone and ceftriaxone are exceptions). Most are excreted by the kidney and require dosage adjustment (cefoperazone and ceftriaxone are exceptions).

THERAPEUTIC USES A wide variety of serious infections caused by organisms resistant to other drugs. A wide variety of serious infections caused by organisms resistant to other drugs. Gonorrhea.Gonorrhea. Meningitis.Meningitis.

THERAPEUTIC USES- Ceftazidime In neutropenic febrile immunocompromised patients (with an aminoglycoside). In neutropenic febrile immunocompromised patients (with an aminoglycoside).

FOURTH GENERATION - Cefepime Similar to the 3 rd gen. cpds, but more resistant to hydrolysis by some  - lactamases. Similar to the 3 rd gen. cpds, but more resistant to hydrolysis by some  - lactamases.

PHARMACOKINETICS Good penetration into the CSF. Good penetration into the CSF. Cleared mainly by the kidneys. Cleared mainly by the kidneys.

THERAPEUTIC USES Similar to the third generation cephalosporins. Similar to the third generation cephalosporins.

DRUG INTERACTIONS Alcohol- disulfiram effect Alcohol- disulfiram effect

CEPHALOSPOR IN ANTIBACTERIAL ACTIVITY THERAPEUTIC USES Cefazolin (1) Streptococci, Staph Gram + Infs. Cefoxitin (2) Gram – orgs, some Gram + orgs. Variety of Gram – infs, mixed aerobic/anaerobic infs. Ceftriaxone(3a) Expanded Gram - coverage Meningitis, gonorrhea, serious gram- infs. Cefoperazone (3b) Pseudomonas Pseudomonal Infs. Cefepime (4) Similar to 3 rd. Gen Similar to 3 rd Gen COMPARISON OF THE CEPHALOSPORINS.

CARBAPENEMS IMIPENEM IMIPENEM Meropenem Meropenem Ertapenem Ertapenem

ANTIBACTERIAL SPECTRUM Broadest antimicrobial spectrum of any  lactam antibiotic. Broadest antimicrobial spectrum of any  lactam antibiotic. Organisms resistant to other types of antibiotics. Organisms resistant to other types of antibiotics.

MECHANISM OF ACTION Similar to other  lactams. Similar to other  lactams. Resistant to hydrolysis by  lactamases. Resistant to hydrolysis by  lactamases.

PHARMACOKINETICS Not absorbed orally; usually given IV. Not absorbed orally; usually given IV. Predominantly excreted by the kidneys. Predominantly excreted by the kidneys. Hydrolyzed by a renal tubular enzyme (dehydropeptidase) so given combined with cilastatin. Hydrolyzed by a renal tubular enzyme (dehydropeptidase) so given combined with cilastatin.

THERAPEUTIC USES Infections caused by multi-drug resistant organisms. Infections caused by multi-drug resistant organisms. Serious mixed infections. Serious mixed infections.