Cephalosporins Flashcards
Cephalosporins
Beta-lactams structurally related to penicillins, 6-Membered dihydrothiazine ring in place of 5-Membered thiazolidine ring, Modification at 7-position alter antibacterial activity but at 3-alter pharmacokinetics, Bactericidal, Similar to penicillins, Classified by generations
Cefazolin
Ancef
First (Narrow Spectrum)
Injection
Streptococci (except penicillin resistant strains), S. aureus (except MRSA)
RECOMMENDED BY AHA for premed prophylaxis in penicillin-allergic patients unable to take oral med
Alt. for methicillin group
Cephalothin
Keflin
First (Narrow Spectrum)
Injection
Streptococci (except penicillin resistant strains), S. aureus (except MRSA)
Cephalexin
Keflex
First (Narrow Spectrum)
Oral
Streptococci (except penicillin resistant strains), S. aureus (except MRSA)
USED IN DENTISTRY TO PREVENT JOINT INFECTION (Total joint replacement surgery, Dental procedures - Tooth extractions, Gum surgery, Professional cleanings and Orthodontic band)
Cephadroxyl
Duricef
First (Narrow Spectrum)
Oral
Streptococci (except penicillin resistant strains), S. aureus (except MRSA)
Cefuroxime
Ceftin
Second (Intermediate Spectrum)
Injection
E. Coli, Klebsiella, Proteus, H. Influenzae, M. Catarrhalis, Less active VS Gram + than 1st gen
Cefaclor
Ceclor
Second (Intermediate Spectrum)
Oral
E. Coli, Klebsiella, Proteus, H. Influenzae, M. Catarrhalis, Less active VS Gram + than 1st gen
Cefoxitin
Mefoxin
Second (Intermediate Spectrum)
Injection
Inferior to Cefuroxime VS S. aureus but increased activity VS Bacteroides fragilis and other Bacteriodes spp.
Cefotetan
Cefotan
Second (Intermediate Spectrum)
Injection
Inferior to Cefuroxime VS S. aureus but increased activity VS Bacteroides fragilis and other Bacteriodes spp.
Agents containing Methylthiotetrazole (MTT) side chain (cefotetan) interfere w/ Vit K metabolism and cause clotting problems - Use with caution in patients on warfarin or with underlying clotting problems, Agents also cause disulfiram like rxn with alcohol
Ceftriaxone
Rocephin
Third
Injection
Enterobacteriaceae, Pseudomonas aeruginosa, Serratia, Neisseria gonorrhoeae, Activity VS S. aureus, Strep. Pneumoniae and Strep. Pyogenes comparable to 1st gen. Activity VS Bacteroides inferior to cefoxitin and cefotetan
AHA RECOMMENDED as injectable premedication for penicillin allergic patients unable to take oral meds
Cefotaxime
Claforin
Third
Injection
Enterobacteriaceae, Pseudomonas aeruginosa, Serratia, Neisseria gonorrhoeae, Activity VS S. aureus, Strep. Pneumoniae and Strep. Pyogenes comparable to 1st gen. Activity VS Bacteroides inferior to cefoxitin and cefotetan
Ceftazidime
Fortaz Third Injection Enterobacteriaceae, Pseudomonas aeruginosa, Serratia, Neisseria gonorrhoeae, Activity VS S. aureus, Strep. Pneumoniae and Strep. Pyogenes comparable to 1st gen. Activity VS Bacteroides inferior to cefoxitin and cefotetan ACTIVE VS. PSEUDOMONAS
Ceftizoxime
Cefizox
Third
Injection
Enterobacteriaceae, Pseudomonas aeruginosa, Serratia, Neisseria gonorrhoeae, Activity VS S. aureus, Strep. Pneumoniae and Strep. Pyogenes comparable to 1st gen. Activity VS Bacteroides inferior to cefoxitin and cefotetan
Cefpodoxime proxetil
Vantin
Third
Oral
Enterobacteriaceae, Pseudomonas aeruginosa, Serratia, Neisseria gonorrhoeae, Activity VS S. aureus, Strep. Pneumoniae and Strep. Pyogenes comparable to 1st gen. Activity VS Bacteroides inferior to cefoxitin and cefotetan
Cefeprime
Maxipime
Fourth
Injection
Comparable to third-gem but more resistant to some Beta-lactamases
Zwitterion - Enhanced ability to penetrate porin in outer membrane of Gram - bacteria
First Generation Cephalosporins
Greatest activity VS Gram + (Few Gram - P. mirabilis, E. coli, K. pneumoniae), Good bone penetration and greater activity VS Staph., Excellent for joint prosthesis prophylaxis, More stable to bacterial beta-lactamase (Cefazolin for Methicillin group) but not good activity VS Anaerobes (Bacteroides), Excretion by glomerular filtration and tubular secretion, Probenacid will increase serum levels (Blocks tubular secretion), Adjust dose in renal impairment
Second Generation Cephalosporins
Expanded activity against Gram - including cephalothin resistant E.coli, Klebsiella and P. mirabilis, Increased spectrum of action due to greater affinity for PBP, Greater penetration of Gram - envelope and Greater resistance to Beta-lactamase hydrolysis, Cephamycins (Cefoxitin) are active against Bacteroides fragilis and Serratia marcescens - Useful to treat mixed anaerobic infections
Third Generation Cephalosporins
Good activity VS many Gram - organisms (Enterobacteriaceae, H. influenzae and N. gonorrhoea), Increased Gram - activity due to addition of aminothiazole moiety to beta lactam ring, Good CSF level for treating bacterial meningitis, Ceftazidime and Cefoperazone active VS Pseudomonas, Sensitive to some beta-lactamases from Enterobacter
Fourth Generation Cephalosporins
Similar to third but active VS Pseudomonas aeruginosa and organisms resistant to third gen agents, Greater resistance to beta-lactamase than third, Chemical modification at position 7 renders agents more stable against beta-lactamase
Fifth Generation Cephalosporins
Ceftaroline (Teflaro) and Ceftobiprole (Future - Not available in US), Active VS Multidrug resistant S. aureus including MRSA, VISA, VRSA, Increased binding to PBP2a responsible for MRSA, Administered IV,
Ceftaroline - Community acquired pneumonia and skin infections
Cephalosporin Mechanism of Action
Similar to Penicillin, Inhibit cell wall synthesis
Cephalosporin Pharmacokinetics
Cephalosporins of third gen useful for meningitis by Gram - organisms, First and Second gen do not enter CSF in adequate concentrations, Most excreted by active transport in liver
Cephalosporins Adverse Effects
Intrathecal admin may cause convulsions, Agents containing Methylthiotetrazole (MTT) side chain (cefotetan) interfere w/ Vit K metabolism and cause clotting problems - Use with caution in patients on warfarin or with underlying clotting problems, Agents also cause disulfiram like rxn with alcohol; Allergic rxns, cross allergenicity to penicillins
Azetreonam Chemistry
Monocyclic lactam w/unique spectrum of action
Azetreonam Spectrum of Action
Active VS Most Gram - bacteria including P. aeruginosa, No activity VS Gram +, Resistant to some Gram - Beta-lactamase, Effective VS P. aeruginosa, Enterobacteriaceae, H. influenzae and Gonococci
Azetreonam Uses
Useful in patients with serious penicillin allergy who have infections caused by resistant Gram - organisms
Azetreonam Mechanism of Action
Possess a sulfonic acid group attached to N at 1-Position in structure that causes it to bind preferentially to PBP-3 of Gram - bacteria
Azetreonam Pharmacokinetics
Poorly absorbed from gut as it is converted to an inactive ring form by intestinal flora, Must be administered IM or IV, Well distributed including CNS, Largely excreted unchanged and eliminated by filtration and tubular secretion, Short t1/2 so frequent dosing necessary, also causes IV site phlebitis
Azetreonam Adverse Effects
Similar to other beta-lactams, Pain at site of injection, rash, GI discomfort in form of nausea, vomiting, diarrhea, Alternative to patients allergic to penicillins
Daptomycin Mechanism of Action
Unclear, but seems like daptomycin integrates into cell membrane and oligomerize to form pores, resulting in K+ efflux, membrane depolarization and cell death, Given IV, Active VS Gram + organisms, Used to treat complicated skin infections, bacteremia or endocarditis from S. Aureus, Active VS MRSA
Daptomycin Adverse Effects
Myopathy, Eosinophilic pneumonia, AAC (C. difficile diarrhea), Do not administer Daptomycin with statin drugs due to common adverse effect of myopathy
Bacitracin Spectrum of Action
Topical polypeptide antibiotic, Bactericidal VS Gram + cocci and bacilli, Group A Streptococci are very sensitive
Bacitracin Mechanism of Action
Inhibit cell wall synthesis by inhibiting lipid carrier involved in murein monomer synthesis, Zn2+ or Mg2+ required
Bacitracin Uses
Used topically for skin, eye and mucus membrane infections caused mainly by group A Streptococci and Staphylococci
Bacitracin Pharmacokinetics
Not absorbed orally so remain in gut lumen and occasionally used to treat C. difficile colitis or eradicate vancomycin-resistant enterococci in GI tract
Bacitracin Adverse Effect
Significant kidney, bone marrow and neurological effects so not generally used systemically
Mupirocin
Bactroban 2%
Unique action, Irreversible binding to bacterial isoleucyl t-RNA synthetase blocking protein and RNA synthesis, Topical use for S. aureus skin infections and intra-nasal to treat health worker carriers of MRSA, Bacteriocidal only at high conc., Rare anapylactoid reactions and AAC
Fosfomycin Spectrum of Action
Active VS many Gram + and - Bacteria, Used as single dose for uncomplicated lower urinary tract infection in women
Fosfomycin Mechanism of Action
Inhibits first step in synthesis of peptidoglycan
Fosfomycin Pharmacokinetics and Adverse Effects
Administered orally, Excreted in urine, Safe in pregnancy, Minimal side effects
Cycloserine Spectrum of Action
Used to treat TB that is resistant to first line agents, Active VS Gram + and - organisms
Cycloserine Mechanism of Action
Structural analogue of D-Ala that inhibit cell wall synthesis by irreversible inhibiting both the alanine racemase that converts L-Ala to D-Ala, and D-Ala-D-Ala ligase that joins together 2 D-Ala. This prevents incorporation of D-Ala into peptidoglycan pentapeptide
Cycloserine Pharmacokinetics
Widely distributed in tissue, Excreted in urine as active drug
Cycloserine Adverse Effects
Causes serious dose related CNS toxicity w/ headaches, seizures, peripheral neuropathy, tremors and psychosis, Toxicity potentiated by alcohol, isoniazid and ethionamide, Cyclosporine inhibit metabolism of phenytoin
Penicillin VK Dose
Child: 25-50mg/kg body weight q6h or q8h for 7days; Max dose - 3g/day
Adult: 500mg q6h for 7 days
Clindamycin Dose
Child: 8-25mg/kg in 3-4 doses
Adult: 150-450mg q6h for 7 days, Max dose - 1.8g/day
Amoxicillin Dose
Child: 20-40mg/kg/day q8h if <40kg; 250-500mg q8h or 875mg q12h for 7 days; Max dose - 2g/day
Adult: 250-500mg q8h or 875mg q12h for 7 days; Max dose - 2g/day
Cephalexin Dose
Child: 25-50mg/kg/day in q6h; Severe infection - 50-100mg/kg/day in q6h; Max dose - 3g/24h
Adult: 250-1000mg q6h; Max dose - 4g/day
Augmentin - Amoxicillin/Clavulanic Acid
Child: 20-40mg/kg/day in q8h if <40kg; 250-500 mg/kg/day in q8h or 875mg q12h for 7 days; Max dose - 2g/day
Adult: 250-500mg q8h or 875mg q12h for 7 days; Max dose - 2g/day
