CephalosporinsCephalosporins

B-Lactam antibiotics ( similar to penicillins)B-Lactam antibiotics ( similar to penicillins)Broad spectrumBroad spectrumAct by inhibition of cell wall synthesisAct by inhibition of cell wall synthesisBactericidalBactericidalInactive against : enterococci, MRSA, Inactive against : enterococci, MRSA, legionella , mycoplasma, chlamydia spp. legionella , mycoplasma, chlamydia spp. Widely used in surgical procedures to Widely used in surgical procedures to reduce the risk of post operative infections reduce the risk of post operative infections

Classifications of cephalosporinsClassifications of cephalosporins

FIRST GENERATIONFIRST GENERATION

Cephalexin , poCephalexin , po CefazolinCefazolin

CephalothinCephalothin Cephradine , poCephradine , po

Active against G+ cocci ( except.enterococci & MRSA )Active against G+ cocci ( except.enterococci & MRSA ):: s.pneumoniae, s.pyogenes,s. aureus, s. s.pneumoniae, s.pyogenes,s. aureus, s.

epidermidis epidermidis Indicated for streptococcal pharyngitis ( e.g. cephalexin)Indicated for streptococcal pharyngitis ( e.g. cephalexin)

Commonly used ( eg. Cefazolin) as prophylacic for Commonly used ( eg. Cefazolin) as prophylacic for surgical proceduressurgical procedures..

Modest activity against G- bacteriaModest activity against G- bacteria

SECOND GENERATIONSECOND GENERATIONCefoxitin ( mefoxin )Cefoxitin ( mefoxin )Cefuroxime ( zinacef ) Cef. axetil ( zinnat )Cefuroxime ( zinacef ) Cef. axetil ( zinnat )Cefaclor ( ceclor ) Cefprozil ( cefzil )Cefaclor ( ceclor ) Cefprozil ( cefzil ) Mainly effective against G- bacteriaMainly effective against G- bacteriaModest activity against G+ bacteriaModest activity against G+ bacteria

CefoxitinCefoxitin active against bowel anaerobes (B. fragilis ) active against bowel anaerobes (B. fragilis ) Cefuroxim Cefuroxim active against H. influenzae, M. catarrhalis, S. pneumoniaeactive against H. influenzae, M. catarrhalis, S. pneumoniaeCef. Axetil-Cef. Axetil- oral form of cefuroxim oral form of cefuroximCefaclorCefaclor active against H. influenzae, M. catarrhalis &E.coli active against H. influenzae, M. catarrhalis &E.coliCefprozilCefprozil- similar to cefaclor, c. axetil and augmentin- Liked by children- similar to cefaclor, c. axetil and augmentin- Liked by childrenSecond Generations are used primarily for URTIs ( acute otitis media, Second Generations are used primarily for URTIs ( acute otitis media, sinusitis ) and Lower RTIs ( acute exacerbation of chronic sinusitis ) and Lower RTIs ( acute exacerbation of chronic bronchitis)bronchitis)

THIRD GENERATIONTHIRD GENERATIONCeftriaxone ( rocephin )Ceftriaxone ( rocephin )Cefotaxime ( claforan )Cefotaxime ( claforan )Cetazidime ( fortum )Cetazidime ( fortum )Cefoperazone ( cefobid )Cefoperazone ( cefobid )Cefixime ( suprax )Cefixime ( suprax )

They have enhanced G- activity, H. influenzae, N. meningitidis, N.gonorrhea, They have enhanced G- activity, H. influenzae, N. meningitidis, N.gonorrhea, P. aeruginosae, M. catarrhalis, E.coli, most KlebsiellaP. aeruginosae, M. catarrhalis, E.coli, most KlebsiellaCeftriaxoneCeftriaxone has long half-life . Not advised in neonates (interferes with bilirubin has long half-life . Not advised in neonates (interferes with bilirubin metabolism )metabolism )Cefotaxime Cefotaxime preferred in neonate ( does not interfere with bilirubin metabolism ), preferred in neonate ( does not interfere with bilirubin metabolism ), as may ceftriaxoneas may ceftriaxone..Ceftazidime Ceftazidime & & cefoperazonecefoperazone have excellent activity against p. aeruginosae have excellent activity against p. aeruginosae..CefiximeCefixime has similar activity to amoxicillin & cefaclor for actute otitis media has similar activity to amoxicillin & cefaclor for actute otitis media

Fourth GenerationFourth GenerationCefipimeCefipime

Active against G+ bacteria than cefazolin Active against G+ bacteria than cefazolin against s. pyogenes, s.pneumoniae but against s. pyogenes, s.pneumoniae but lower against s. aureus. lower against s. aureus. Similar to cefotaxime against E.coli & K. Similar to cefotaxime against E.coli & K. pneumoniae but for p. aeruginosapneumoniae but for p. aeruginosa..

PharmacokineticsPharmacokineticsCephalosporins are given parenterally and orallyCephalosporins are given parenterally and orally..

Extent of binding to plasma protein vary from one to anotherExtent of binding to plasma protein vary from one to another.. e.g. Cefazolin is 80% protein bound ( hence, long t1/2 )e.g. Cefazolin is 80% protein bound ( hence, long t1/2 )

Cephalexin is 10-15% protein boundCephalexin is 10-15% protein bound

Relatively lipid insoluble ( like penicillins )Relatively lipid insoluble ( like penicillins )Hence,do not penetrate cells or the CNS, except for third generationsHence,do not penetrate cells or the CNS, except for third generations..

Mostly excreted unchanged by the kidney (glomerular & tubular Mostly excreted unchanged by the kidney (glomerular & tubular secretion ), except, ceftazidime & cefoperazone( glomerular)secretion ), except, ceftazidime & cefoperazone( glomerular)

Probenecid slows their elimination and prolong their half-live ( except Probenecid slows their elimination and prolong their half-live ( except Ceftazidime & cefoperazone)Ceftazidime & cefoperazone)

Half-life 30-90 min; ceftriaxone 4-7 hrHalf-life 30-90 min; ceftriaxone 4-7 hr

Therapeutic usesTherapeutic uses11 . .Alternative to penicillin in allergic Alternative to penicillin in allergic

patients patients

22 . .Upper respiratory tract infections Upper respiratory tract infections and otitis media and otitis media

cefaclor cefuroxime axetilcefaclor cefuroxime axetil cefixime cefprozilcefixime cefprozil

33 . .Septicaemia caused by G- bacteria Septicaemia caused by G- bacteria ( P.aeruginosae) ( P.aeruginosae)

A penicillin(eg.Piperacillin/ A penicillin(eg.Piperacillin/ Ticarcillin) +aminoglycoside Ticarcillin) +aminoglycoside

OROR A cephalosporin(eg. A cephalosporin(eg.

ceftazidime ) + AG ceftazidime ) + AG44 . .Urinary tract infectionsUrinary tract infections

Cefuroxime, CefiximeCefuroxime, Cefixime

. .55 . .Prophlaxis in surgeryProphlaxis in surgery Appendectomy ( bowel Appendectomy ( bowel

anaerobes ) eg. Cefoxitin anaerobes ) eg. Cefoxitin Obstetrical &gynecological, Obstetrical &gynecological,

urological, orthopedic urological, orthopedic procedures, etc procedures, etc

) ) S. aureus & S. epidermidisS. aureus & S. epidermidis ( ( eg. Cefazolineeg. Cefazoline

66 . .Meningitis- N. MeningitidisMeningitis- N. Meningitidis CeftriaxoneCeftriaxone

Cefotaxime( pref. in neonate)Cefotaxime( pref. in neonate)

77 . .Gonococcal infectionsGonococcal infections CeftriaxoneCeftriaxone

Adverse effectsAdverse effects

11 . .Hypersensitivity reactions- most commonHypersensitivity reactions- most common Anaphylaxis, bronchspasm, urticariaAnaphylaxis, bronchspasm, urticaria Maculopapular rash- more commonMaculopapular rash- more common

22 . .Nephrotoxicity ; esp. cephradineNephrotoxicity ; esp. cephradine33 . .Thrombophlebitis ( i.v admin. )Thrombophlebitis ( i.v admin. )

44 . .SuperinfectionsSuperinfections55 . .Diarrhea-oral cephalosporins, cefoperazone, Diarrhea-oral cephalosporins, cefoperazone,

ceftriaxone & moxalactam ceftriaxone & moxalactam . .66 . .cefamandole, moxalactam & cefoperazone may causecefamandole, moxalactam & cefoperazone may cause::

a) bleeding disordersa) bleeding disorders b) Flushing, tachycardia, vomiting with alcohol intakeb) Flushing, tachycardia, vomiting with alcohol intake