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CEPHALOSPORINS AND CEPHAMYCINSAND CEPHAMYCINS
Dr. Deepak K Gupta
Introduction• Cephalosporins N, C or P - steroidal antibiotic that
resembles fusidic acid.
• first isolated from Cephalosporium fungus
• Semisynthetic broad-spectrum cephalosporins -produced by addition, to the cephalosporin C produced by addition, to the cephalosporin C nucleus
• water-soluble and relatively acid-stable
• cephamycins are β-lactam antibiotics -Streptomyces organisms– closely related to the cephalosporins
Generations of CephalosporinOral Parentral
1st generation
Cephalexin Cephalothin
Cephradine Cefazolin
Cefadroxil
2nd generation
Cefaclor CefuroximeCefaclor Cefuroxime
Cefuroxime axetil Cefoxitin
3rd generation
Cefixime Cefotaxime
Cefdinir Ceftizoxime
Ceftibuten Ceftriaxone
Ceftamer pivoxil Ceftazidime
4th generation
Cefepime
Cefpirome
Mechanism of action
• Similar to that of the penicillins
• Interference with bacterial peptidoglycansynthesis
• Resistance to this group of drugs has • Resistance to this group of drugs has increased - plasmid-encoded or chromosomal β-lactamase in bacteria
1st Generation1 Generation
First Generation Cephalosporin• Active against gram-positive cocci, such as
pneumococci, streptococci, and staphylococci.• Traditional cephalosporins - not active against MRSA
strain.• E coli, K pneumoniae , and Proteus mirabilis are often
sensitivesensitive• Clinical Use– drug of choice for surgical prophylaxis– urinary tract infections– cellulitis or soft tissue abscess– cannot be used to treat meningitis– Alternative to penicillin allergic individual
Cefazolin
• 1st cephalosporin – active against most PnGsensitive organism
• Streptococci, gonococci , meningococci, C. diptheriae, H. influenzae, clostrodia and ActinomycesActinomyces
• Given I.M. or I.V., longer t1/2 – 2hrs – slow tubular secretion
• Preferred parentral – 1st generation ceph
• Dose : 0.25 g X 8 hrs - mild, 1 g X 6 hrs - severe
Cephalexin
• 1st oral ceph, similar to cefazolin but less active against penicillinase producing Staphylococci and H. influenza.
• Little bound to plasma proteins – high • Little bound to plasma proteins – high concentration in bile
• t ½ - 60 min
• Most commonly used cephalosporin
• 0.25 – 1 g – (6 - 8 hrs), child : 25-100 mg/kg/day
Cefadroxil
• Close congener of cephalexin, antibacterial similar
• Good tissue penetration – sustained action at the site of infectionthe site of infection
• t ½ - 1 hr.
• Excreted unchanged on urine.
• Dose: 0.5 – 1 g BD
Second Generation
Second generation Cephalosporin
• More active against gram negative organism, with some members active against anerobes
• But none inhibits P. aeruginosa.• Replaced by third generation – more active• Clinical Use• Clinical Use– treat sinusitis, otitis, and lower respiratory tract
infections– treat mixed anaerobic infections such as peritonitis,
diverticulitis, and pelvic inflammatory disease– community-acquired pneumonia– less effective in treatment of meningitis
Cefuroxime
• Resistance to gram negative beta-lactamase
• Highly active against PnG and ampicillinresistant H. influenza.
• Well tolerated by i.m. route and attains • Well tolerated by i.m. route and attains relatively higher level in CSF (ideal for meningitis)
• Single dose i.m. theraphy – Gonorrhoea
• Dose : 0.75 – 1.5 g i.m. or i.v. 8hrly, Child : 30-100 mg/kg/day
Cefuroxime axetil
• Esters of cefuroxime
• Effective orally – absorption is incomplete
• Activity depends on in vivo hydrolysis and release of cefuroxime.release of cefuroxime.
• Dose: 250-500 mg BD, Child: half dose
Cefaclor
• Significant activity by oral route
• More active than first generation compound again H. influenzae, E. coli, and Pr. Mirabilis
• Dose: 0.25 -1.0 g X 8 hrly• Dose: 0.25 -1.0 g X 8 hrly
3rd generation Cephalosporin3rd generation Cephalosporin
3rd generation Cephalosporin
• Expanded gram-negative coverage, and some are able to cross the blood-brain barrier
• Also effective against β-lactamase-producing strains of haemophilus and neisseria.
• Ceftazidime and cefoperazone are the• Ceftazidime and cefoperazone are theonly two drugs with useful activity against P. aeruginosa.
• Not reliably active against Enterobacter species -hydrolyzed by β lactamase.
• Serratia, Providencia and Citrobacter -cephalosporinase
Clinical Use
• Treat a wide variety of serious infections caused by organisms that are resistant to most other drugs
• avoided in treatment of enterobacter infections• Ceftriaxone and cefotaxime - meningitis, including
meningitis caused by pneumococci, meningococci, meningitis caused by pneumococci, meningococci, H influenzae and susceptible enteric gram-negative rods, but not by L-monocytogenes
• empirical therapy of sepsis of unknown cause inboth the immunocompetent and the immunocompromised patient
• Hospital Acquire infection
Cefotaxime
• Prototype of 3rd generation ceph.
• Potent action – aerobic gram-negative as well as some gram positive bacteria, but not active against anaerobes ( S. aureus, Ps. aeruginosa)against anaerobes ( S. aureus, Ps. aeruginosa)
• Single dose therapy – urethritis
• T ½ - 1 hr
• Dose : 1-2 gm i.m/i.v 8-12 hrly, child dose : 50-100 mg/kg/day
Cefixime
• Orally active 3rd generation ceph
• Highly active against Enterobacteriacae, H. influenzae, but resistant to beta-lacatmaserelasing microbes ( S. aureus, most pneumococci & Pseudomonas)pneumococci & Pseudomonas)
• Respiratory, urinary and bilary infection
• T ½ - 3 hr
• Stool changes and diarrhoea – s/e
• Dose : 200-400 mg BD, Child dose : half
4th generation Cephalosporin4 generation Cephalosporin
4th generation Cephalosporin
• more resistant to hydrolysis by chromosomalβ lactamases - Enterobacter
• Like the third-generation compounds, it is hydrolyzed by extended spectrum β hydrolyzed by extended spectrum β lactamases
CEFEPIME• Similar to 3rd generation but highly resistant to beta-
lactamase.• Active against many bacteria which used to not get
killed by earlier generation• Enterobacteriacae, H. influenzae, S. aureus, most
pneumococci & Pseudomonas.pneumococci & Pseudomonas.• high potency – serious infection acquired from hospital– Pneumonia– Febrile neutropenia– Bacteraemia– Septicaemia
• Dose: 1-2 gm (50 mg/kg) i.v. 8-12 hrly
Adverse effect of Cephalosporin
• Pain
• Diarrhoea
• Hypersensitivity
• Nephrotoxicity• Nephrotoxicity
• Bleeding
• Neutropenia and thrombocytopenia - rare