cephalosporins and cephamycins
TRANSCRIPT
![Page 1: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/1.jpg)
CEPHALOSPORINS AND CEPHAMYCINSAND CEPHAMYCINS
Dr. Deepak K Gupta
![Page 2: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/2.jpg)
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
![Page 3: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/3.jpg)
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
![Page 4: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/4.jpg)
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
![Page 5: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/5.jpg)
1st Generation1 Generation
![Page 6: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/6.jpg)
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
![Page 7: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/7.jpg)
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
![Page 8: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/8.jpg)
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
![Page 9: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/9.jpg)
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
![Page 10: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/10.jpg)
Second Generation
![Page 11: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/11.jpg)
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
![Page 12: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/12.jpg)
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
![Page 13: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/13.jpg)
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
![Page 14: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/14.jpg)
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
![Page 15: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/15.jpg)
3rd generation Cephalosporin3rd generation Cephalosporin
![Page 16: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/16.jpg)
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
![Page 17: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/17.jpg)
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
![Page 18: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/18.jpg)
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
![Page 19: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/19.jpg)
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
![Page 20: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/20.jpg)
4th generation Cephalosporin4 generation Cephalosporin
![Page 21: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/21.jpg)
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
![Page 22: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/22.jpg)
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
![Page 23: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/23.jpg)
Adverse effect of Cephalosporin
• Pain
• Diarrhoea
• Hypersensitivity
• Nephrotoxicity• Nephrotoxicity
• Bleeding
• Neutropenia and thrombocytopenia - rare
![Page 24: Cephalosporins and cephamycins](https://reader033.vdocuments.us/reader033/viewer/2022042619/58f37e091a28ab64738b4577/html5/thumbnails/24.jpg)