This document provides an overview of cephalosporin antibiotics, including their history, classification, mechanisms of action and resistance, uses, and adverse reactions. Some key points: - Cephalosporins are beta-lactam antibiotics that inhibit bacterial cell wall synthesis. They were first discovered from the fungus Cephalosporium acremonium in 1948. - They are classified into generations based on spectrum of activity. Newer generations have activity against a broader range of bacteria, including some resistant to earlier generations. - They work by inhibiting bacterial cell wall synthesis via binding to penicillin-binding proteins. Resistance can occur via beta-lactamase production or target modification. -

1. PES MODERN COLLEGE OF PHARMACY, FOR LADIES
CEPHALOSPORIN
ANTIBIOTICS
REKHA BHALERAO
ASSISTANT PROFESSOR

2. CEPHALOSPORINS

3. Pointsto be covered:
1. History and Chemistry
2. Classification
3. Mechanism of Action
4. Mechanism of BacterialResistance
5. General features of Cephalosporins
6. Antimicrobial Spectrum & TherapeuticUses
7. Adverse Reactions
8. Current Status

4. History and Chemistry
• Cephalosporin isaβ-LactamAntibiotics.Includinginclassofdrugs
whichinhibit thesynthesisofpeptidoglycanofbacterialcellwall.
• Theseclassinclude: Penicillins,Cephalosporins,Carbapenems
• ThisdrugobtainedfromCephalosporiumacremoniumwhichinvested
inyear1948
• Thisdrugshowsantibacterialactioninvitrofor
bacterialikeS.aureus;staphylococci,italso
usedtotreattyphoidinfections.

5. BACTERIALCELLWALL

6. • Nucleus 7- amino cephalosporanic acid analogous to 6-
aminopenicillanic acid.
• Modification in sidechains gives different derivatives.
• First agent Cefalothin Eli Lilly 1964
History and Chemistry

9. CLASSIFICATION
• FIRST GENERATION: Cephadroxil, Cephalexin, Cephazolin,
Cephalothin
Cefotetan,• SECOND GENERATION: Cefaclor, Ceforanide,
Cefoxitin, Cefprozil, Cefuroxime, Cefuroxime axetil.

10. CLASSIFICATION
• THIRD GENERATION: Cefdinir, Cefditoren pivoxil, Ceftibuten,
Cefixime, Cefotaxime, Cefpodoxime proxetil, Ceftizoxime,
Ceftazidime, Cefoperazone,Ceftriaxone.
• FOURTHGENERATION:Cefepime,Cefpirome
• FIFTHGENERATION:Ceftaroline, Ceftobiprole

11. Mechanism of Action

13. MECHANISM OFBACTERIALRESISTANCE
• Inactivation of antibiotic by β-lactamase
• Modification of targetPBPs
• Impaired penetration of drug totarget PBPs
• Antibiotic efflux

15. General features of Cephalosporins

21. FIFTHGENERATIONCEPHALOSPORINS
• Ceftaroline fosamil
• Nov 2010
• 600mg 12 hrly IVinfusion over 1hr.

22. Antimicrobial Spectrum & TherapeuticUses

23. FIRSTGENERATIONCEPHALOSPORINS
• Gram positive cocci Streptococci, Staphylococci
• Gram negative Moraxella catarrhalis, E.coli, K.pneumonia, P.
mirabilis
• Penicillin susceptible anaerobes in oral cavity except B.fragilis.
• ExceptionEnterococci, MRSA,Penicillin resistantStreptococci,
S.epidermidis

24. FIRSTGENERATIONCEPHALOSPORINS
•USES
• Skin& Soft tissueinfections
• Prophylaxis before surgery (Cefazolin)

25. SECOND GENERATIONCEPHALOSPORINS
• Gram negative aerobesH. influenza, M. catarrhalis, P.mirabilis, E.
coli, Klebsiella, Neisseriagonorrhea
• Gram positive cocciless active
• Anaerobes- B. fragilis
• No efficacy against Pseudomonas, Enterococci
• Cefuroxime, Cefotetan, Cefmetazole lack activity against B. fragilis

26. SECOND GENERATIONCEPHALOSPORINS
• Respiratory tract infections
• Acute sinusitis
• Otitis media
• Uncomplicated UTI
• Cephamycinsmixed aerobic/anerobic infections
• Skin& soft tissues
• Intra abdominal
• Gynecological

27. THIRDGENERATIONCEPHALOSPORINS
• Lessactive than 1st gen against Grampositive organisms.
• More active againstenterobacteriaceae.
• Ceftazidime  P.aeruginosa

28. THIRDGENERATIONCEPHALOSPORINS
• With/without aminoglycoside infections by Klebsiella,
Enterobacter, Proteus, Hemophilus sp,Providencia
• Ceftriaxone all forms of gonorrhea; severe Lymedisease
• Cefotaxime & Ceftriaxone initial Rxofmeningitis
• Ceftazidime+ aminoglycoside Pseudomonas meningitis
• Community Acquired Pneumonia

29. FOURTHGENERATIONCEPHALOSPORINS
• Active against Gram positive, Enterobacteriaceae,
Pseudomonas.
• UsesNosocomial infections
• No activity: penicillin-resistant S. pneumonia, MRSA, MRSE,
Staphylococci, Enterococcus, L. monocytogenes, Legionella
pneumophila, L.micdadei, C.difficile, Campylobacterjejuni.

30. FIFTHGENERATIONCEPHALOSPORINS
 Gram positive cocci MRSA, MRSE, Penicillin Resistant
Streptococcus, Enterococcusfaecalis
 Gramnegative E.coli,Pseudomonas
 Uses-
 Acute Bacterial Skinand SkinStructure Infections

31. Adverse Reactions

32. ADVERSEEFFECTS
• Hypersensitivity reactions
• Immediate anaphylaxis, bronchospasm, urticarial
• LateMaculopapular rash with/without fever, eosinophilia
• Crossreactivity
• Nephrotoxicity

33. ADVERSEEFFECTS
• Antibiotic induced colitis
• Intolerance to alcohol (disulfiram likereaction)
• Thrombocytopenia/ platelet dysfunction
• Rarely,bone marrow depressiongranulocytopenia.

34. Current Status

35. AVYCAZ(CEFTAZIDIME+AVIBACTAM)
• Feb2015
• Complicated Intra-abdominal Infections; UTI
• Dose-2.5g (2g/0.5g) 8 hrly IV infusion over 2hrs
• ADR-nausea,vomiting, constipation, anxiety

36. ZERBAXA(CEFTOLOZANE+TAZOBACTAM)
• Dec2014
• CIAI; UTI
• Dose:1.5g (1g/0.5g) 8 hrly IV infusion over 1hr
• ADR:nausea,diarrhea, headache, pyrexia

37. THANKYOU