Similar to Penicillins: -Chemically. -Mechanism of action. -Toxicity.
Cephalosporins are divided into Generations: -First generation have better activity against gram positive organisms. -Later compounds has improved activity against gram negative anaerobic organisms.
1-First Generation Cephalosporins: -Cefadroxil (Duricef) -Cefazolin -Cephalexin (Keflex) -Cephalothin (Keflin) -Cephradine (Velosef) Very active against gram positive: Pneumococci Streptococci Staphylococci
Not active against MRSA (Methicillin Resistant Staphylococcus Aureus) Proteus, E.coli and Klebsiella are sensitive.
Pharmacokinetics and dosage: -Oral Cephalexin, Cephradine, Cefadroxil Cephalexin is given orally 500 mg four times daily Cefadroxil twice daily Glomerular filtration and tubular secretion Dosage reduced in renal impairment
Parenteral: Cefazolin is used 500-1000 mg 8 hourly IV.
Clinical uses: Rarely drug of choice -UTI -Cellulitis -Soft tissue infection Not relied upon in serious systemic infection
2- Second generation cephalosporins: -Cefaclor (Ceclor) -Cefamandole (Mandol) -Cefuroxime (Zinacef, Zinnat) -Cefprozil Active against organisms affected by first generation = extended gram negative coverage Klebsiella and H.influenzae are usually sensitive.
Second generation are less active on gram positive than first generation Non are active against Pseudomonas aeruginosa.
Oral -Cefaclor -Cefuroxime axetil -Cefprozil. Except Cefuroxime axetil these drugs are not predictably active against penicillin resistant pneumococci Used cautiously to treat pneumococcal infection
Dose adjustment is important in renal failure Clinical uses: -Sinusitis -Otitis media -Lower respiratory tract infection
Cefuroxime is used in community acquired pneumonia. Beta lactamase producing H.influenzae Klebsiella are usually sensitive.
3-Third generation cephalosporins: -Cefotaxime. (Claforan) -Ceftazidime. -Ceftriaxone. (Rocephin) -Cefixime. (Suprax) Expanded gram negative coverage ability of some to cross Blood Brain Barrier and some are active against Pseudomonas aeruginosa.
Ceftriaxone Half Life = 7-8 hours and can be injected once every 24 hours. A single daily dose is useful for any infection 4 grams daily dosage can be used to treat meningitis
Cefixime (Suprax) can be given orally 200 mg 400 mg once daily Suprax Ceftriaxone is excreted by the bile And no dose adjustment is required in renal failure.
Clinical Uses: Wide variety of serious infections Ceftriaxone and Cefixime are drug of choice in gonorrhea. Single dose. Commonly misused to treat trivial infection Can be used to treat meningitis
Clinical uses: Penicillin resistant pneumococci Sepsis of unknown cause Neutropenic febrile immune-compromised patients Used in combination with aminoglycoside
4-Fourth generation cephalosporins: -Cefepime More resistant to beta-lactamase Good activity against Pseudomonas aeruginosa Staph aureus Streptococcus pneumonia
Adverse effects: 1-Allergic reactions: -Hypersensitivity reactions similar to penicillins -Anaphylaxis -Fever -Skin rashes -Hemolytic anemia Cross allergy is 5-10 %
Adverse effects: Others adverse reactions including: -Local irritation. -Pain after IM injection. -Thromophlebitis after IV injection. -Nausea and vomiting after rapid IV injection. -Interstitial nephritis. -Super infection of resistant micro organisms can occur.
Other Beta-Lactam Antibiotics: 1-Carbapenems: Structurally related to beta-lactum antibiotics. A- Imipenem. B- Meropenem.
Other Beta Lactam Antibiotics: Imipenem has wide spectrum of activity. -Gram positive -Gram negative, and Anaerobes. Meropenem has slightly less activity against gram positive bacteria.
Other Beta Lactam Antibiotics: Dose of Imipenem is 500 mg 6-8 hourly. Half life = 1 hour Meropenem dose is 1 gm 8 hourly
Other Beta-Lactam Antibiotics: They are used with or without aminoglycoside in febrile Neutropenic patients. Patients allergic to penicillins can be allergic to Imipenem and Meropenem
Other Beta-Lactam Antibiotics: 2-Monobactums: (Aztreonam) Active against gram negative rods (pseudomonas and serratia) No activity against gram positive Aztreonam given iv in dose 1-2 gm IV 8 hourly.
Other inhibitors of cell wall: 1-Vancomycin: -It is a glycopeptide -Is active only against gram positive bacteria. -It is poorly absorbed from the GIT and given orally only in treatment of antibiotic associated enterococci caused by clostridium difficile.
Parenteral dose is given by infusion 90% of the drug is excreted by glomerular filtration Indications: -Infection caused by Methicillin resistant staphylococcus (MRSA) -Enterococcal endocarditis in patient with serious penicillin allergy.
Dose is 1 gm iv 12 hourly Oral Vancomycin is 250 mg 6 hourly Adverse reactions: -Irritation at the site of injection -Chills and fever. -Ototoxicity and nephrotoxicity (Rare) -Red man syndrome due to release of histamine.
Other inhibitors of cell wall: 2-Bacitracin: Is acyclic peptide mixture. Active against gram positive microorganisms. Markedly nephrotoxic. Limited to topical use only.