CEPHALOSPORINSCEPHALOSPORINS
Semisynthetic antimicrobial agents Semisynthetic antimicrobial agents closely related to the penicillins.closely related to the penicillins.
Commercially available Commercially available cephalosporins contain the 7-amino cephalosporins contain the 7-amino cephalosporanic acid nucleus.cephalosporanic acid nucleus.
CLASSIFICATION BY CLASSIFICATION BY GENERATIONGENERATION
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 -FIRST GENERATION -(CEFAZOLIN)(CEFAZOLIN)
Very active vs gram positive cocci.Very active vs gram positive cocci.
Moderate activity against gram Moderate activity against gram negative bacteria.negative bacteria.
PHARMACOKINETICSPHARMACOKINETICS
Do not penetrate the CNS. Do not penetrate the CNS.
Excretion is via the kidney and dose Excretion is via the kidney and dose adjustments must be made for adjustments must be made for impaired renal function.impaired renal function.
THERAPEUTIC USESTHERAPEUTIC USES
Parenteral agents are used primarily Parenteral agents are used primarily for prophylaxis in various surgical for prophylaxis in various surgical procedures.procedures.
Oral drugs used for minor staph Oral drugs used for minor staph infections or some polymicrobial infections or some polymicrobial infections.infections.
THERAPEUTIC USESTHERAPEUTIC USES
Occasionally for gram negative Occasionally for gram negative infections.infections.
SECOND GENERATION-SECOND GENERATION-(CEFOXITIN)(CEFOXITIN)
Extended gram negative coverage Extended gram negative coverage (less active vs gram positive (less active vs gram positive organisms).organisms).
PHARMACOKINETICSPHARMACOKINETICS
Several orally and parenterally Several orally and parenterally available (cefoxitin-IV).available (cefoxitin-IV).
Poor penetration into the CNS.Poor penetration into the CNS.
Dosage adjustments must be made Dosage adjustments must be made in renal failure.in renal failure.
THERAPEUTIC USESTHERAPEUTIC USES
Variety of gram negative infections.Variety of gram negative infections.
THIRD GENERATION –THIRD GENERATION –Ceftriaxone and ceftazidimeCeftriaxone and ceftazidime
Expanded gram-negative coverage. Expanded gram-negative coverage.
CefoperazoneCefoperazone and and ceftazidime ceftazidime have have excellent activity vs excellent activity vs Pseudomonas.Pseudomonas.
PHARMACOKINETICSPHARMACOKINETICS
Cross the blood brain barrier well.Cross the blood brain barrier well.
Half-lives and the necessary dosing Half-lives and the necessary dosing intervals vary greatly (ceftriaxone once intervals vary greatly (ceftriaxone once every 24h).every 24h).
Most are excreted by the kidney and Most are excreted by the kidney and require dosage adjustment (cefoperazone require dosage adjustment (cefoperazone and ceftriaxone are exceptions). and ceftriaxone are exceptions).
THERAPEUTIC USESTHERAPEUTIC USES
A wide variety of serious infections A wide variety of serious infections caused by organisms resistant to caused by organisms resistant to other drugs.other drugs.
• Gonorrhea.Gonorrhea.
• Meningitis.Meningitis.
THERAPEUTIC USES-THERAPEUTIC USES-CeftazidimeCeftazidime
In neutropenic febrile In neutropenic febrile immunocompromised patients (with immunocompromised patients (with an aminoglycoside).an aminoglycoside).
FOURTH GENERATION -FOURTH GENERATION -CefepimeCefepime
Similar to the 3Similar to the 3rdrdgen. cpds, but more gen. cpds, but more resistant to hydrolysis by some resistant to hydrolysis by some --lactamases.lactamases.
PHARMACOKINETICSPHARMACOKINETICS
Good penetration into the CSF.Good penetration into the CSF.
Cleared mainly by the kidneys.Cleared mainly by the kidneys.
THERAPEUTIC USESTHERAPEUTIC USES
Similar to the third generation Similar to the third generation cephalosporins.cephalosporins.
DRUG INTERACTIONSDRUG INTERACTIONS
Alcohol- disulfiram effectAlcohol- disulfiram effect
CEPHALOSPORICEPHALOSPORINN
ANTIBACTERIAL ANTIBACTERIAL ACTIVITYACTIVITY
THERAPEUTIC THERAPEUTIC USESUSES
Cefazolin (1)Cefazolin (1) Streptococci, StaphStreptococci, Staph Gram + Infs.Gram + Infs.
Cefoxitin (2)Cefoxitin (2) Gram – orgs, some Gram – orgs, some Gram + orgs.Gram + orgs.
Variety of Gram – Variety of Gram – infs, mixed infs, mixed aerobic/anaerobic aerobic/anaerobic infs.infs.
CeftriaxoneCeftriaxone
(3a)(3a)
Expanded Gram - Expanded Gram - coveragecoverage
Meningitis, Meningitis, gonorrhea, serious gonorrhea, serious gram- infs.gram- infs.
Cefoperazone Cefoperazone (3b)(3b)
PseudomonasPseudomonas Pseudomonal Infs.Pseudomonal Infs.
Cefepime (4)Cefepime (4) Similar to 3Similar to 3rdrd. Gen. Gen Similar to 3Similar to 3rdrd Gen Gen
COMPARISON OF THE CEPHALOSPORINS.COMPARISON OF THE CEPHALOSPORINS.
CARBAPENEMSCARBAPENEMS
IMIPENEMIMIPENEM
MeropenemMeropenem
ErtapenemErtapenem
ANTIBACTERIAL SPECTRUMANTIBACTERIAL SPECTRUM
Broadest antimicrobial spectrum of Broadest antimicrobial spectrum of any any lactam antibiotic.lactam antibiotic.
Organisms resistant to other types of Organisms resistant to other types of antibiotics. antibiotics.
MECHANISM OF ACTIONMECHANISM OF ACTION
Similar to other Similar to other lactams.lactams.
Resistant to hydrolysis by Resistant to hydrolysis by lactamases.lactamases.
PHARMACOKINETICSPHARMACOKINETICS
Not absorbed orally; usually given IV.Not absorbed orally; usually given IV.
Predominantly excreted by the Predominantly excreted by the kidneys.kidneys.
Hydrolyzed by a renal tubular Hydrolyzed by a renal tubular enzyme (dehydropeptidaseenzyme (dehydropeptidase) ) so given so given combined with cilastatin.combined with cilastatin.
THERAPEUTIC USESTHERAPEUTIC USES
Infections caused by multi-drug Infections caused by multi-drug resistant organisms.resistant organisms.
Serious mixed infections. Serious mixed infections.