Cephalosporins

Presented toProf:Ghania sayed

Prof:yassin Mohammed

Group (1-15)

Content

A• Introduction and

Definition•Advantage and Disadvantage

•SAR

B •Classification•Mechanism of action

C•Therapeutic uses•Pharmacokinetics•Side effect

INTRODUCTION AND DEFINITION

Wide-spectrumβ-lactumbactericidal, chemical properties being similar to the penicillins

Cephamycins : Streptomyces species or are synthetic derivatives produced by substituting oxygen for sulfur (methoxy group) in cephalosporin nucleus.

Cephalosporium acremonium, containing the common 7-aminocephalosporanic acid nucleus

Advantages and Disadvantages

Advantages1. Non-toxic

2. ↓ risk of allergy.3. More stable in acidic medium [less

ring strain]4. Higher penicillinase

resistance.5. Good activity ≠ G-ve

& G+ve

Disadvantage1. Difficult to isolate

& purify [with highly polar side chain]

2. Lower potency [less strained ring]

3. ↓ absorbed orally.

SAR

Mechanism of action:

Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillin).

Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.

The peptidoglycan layer is important for cell wall structural integrity.

Classifications of cephalosporinsThese has been conventionally classified into four generations.

Based on Generation system

• This is based on chronological sequence of development, but more importantly ,takes into consideration the overall antibacterial spectrum as well as potency.

• First-generation cephalosporins are predominantly active against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria (albeit often with reduced activity against Gram-positive organisms).

First generation:Developed in 1960, active against Gm+ weaker on Gm- orgnisms.• Cephalothin: 1st cephalosporin used. (Parenteral)

active against: Streptococci, Staphylococci, gonococci, meningococci, C.diptheriae and clostridia.

• Cephalexin: Orally active. commonly used. (SPORIDEX)• Cefadroxil: Excellent tissue penetration (cefadrox) Excreted unchanged in urine. Dose adjustment in renal impaired patients.

• Cephazolin: Active against klebsiella and E.coli. (Parenteral) Preferred parenteral 1st gen cephalosporin for

surgical prophylaxis , الجراحيه الوقايه(ALCIZONE/ORIZOLIN)

Second generation:• Cefuroxime: Resistant to Gm- beta lactamase (Parenteral) Important use: meningitis caused by H. influenzae,

• Cefuroxime axetil: Ester of cefuroxime, effective oral Uses: URTI, LRTI, UTI, skin and soft tissue infection

group B streptococci,salmonella, E.coli

(CEFTUM,ZOCEF)

Third generation• Broad-spectrum.• Active against Gm- enterobacteriacae.• Some are anti-pseudomal• Resistant to beta-lactamase.Cefotaxim: (TAXIM/OMNATAX) Prototype of third generation cephalosporin. Widely distributed in body tissues and fluids, penetrates CSF best when

meninges are inflamed.

Uses: Aerobic Gm- bacteria infection, poor on anaerobes (B. fragilis), Staphylococci and pseudomonas.prominent indications: meningitis المخ في السحايا االتهاب

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Ceftriaxone:• Longer duration of action. (MONOCEF/CEFERA)• Good CSF penetration.USES: Bacterial meningitis

Multi-Resistant typhoid feverComplicated Uniary tract infection

Ceftazidime: (CEFZID/TAZID)

• Active against pseudomonas.• Burn.

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Cefoperazone: (CEFOMYCIN/NOVACIP)

• Strong anti-pseudomonal property.• Cidal against S.typhi, B.fragilis.• More susceptible to beta-lactamase.USES: severe urinary, biliary, respiratory, skin-soft tissue infection,

meningitis and septicaemia.

Cefixime: (ORIFIX/TAXIM-O/OMNATAX)

• Orally active 3rd generation• Broad spectrum of action- enterobacteriaceae, H. influenzae, Strep

pyogenes. Not active against Staph and Pseudomonas . Cefpodoxim proxetil. (CEPODEM)

• Orally active 3rd generation• Active against enterobacteriaceae and streptococci.• Excellent outcome in RTI, UTI and soft-tissue infection.Cefdinir: (SEFDIN/ADCEF)• Orally active• Excellent results in pneumonia,COPD,ENT & skin infections.

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Fourth generation:

Cefepime: (CEPIME/MEGAPIME)• Highly resistant to beta-lactamase.• Active against pseudomonas and Staph besides host of organismsUses: Serious life-threatening hospital acquired pneumonia

Febrile neutropenia.Bacterremia and septicaemia.

Cefpirome: (CEFROM/CEFORTH)• Treatment of serious and resistant hospital acquired infections

including septicaemia ,pneumonia.• Covers some Gm+ organisms as well.

PharmacokineticsCephalosporins are given parenterally and orally.

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

Cephalexin is 10-15% protein bound

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

Mostly excreted unchanged by the kidney (glomerular & tubular secretion ), except, ceftazidime & cefoperazone( glomerular)Probenecid slows their elimination and prolong their half-live

( except Ceftazidime & cefoperazone) Half-life 30-90 min; ceftriaxone 4-7 hr

Therapeutic uses1 .Alternative to penicillin in allergic

patients

2 .Upper respiratory tract infections and otitis media

cefaclor cefuroxime axetil cefixime cefprozil

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

A penicillin(eg.Piperacillin/ Ticarcillin) +aminoglycoside

OR A cephalosporin(eg.

ceftazidime ) + AG4 .Urinary tract infections

Cefuroxime, Cefixime

.5 .Prophlaxis in surgery Appendectomy ( bowel

anaerobes ) eg. Cefoxitin Obstetrical &gynecological,

urological, orthopedic procedures, etc

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

6 .Meningitis- N. Meningitidis Ceftriaxone

Cefotaxime( pref. in neonate)

SIDE EFFECT1 .Hypersensitivity reactions- most common

Anaphylaxis, bronchspasm, urticaria Maculopapular rash- more common

2 .Nephrotoxicity ; esp. cephradine3 .Thrombophlebitis ( i.v admin. )

4 .Superinfections5 .Diarrhea-oral cephalosporins, cefoperazone,

ceftriaxone & moxalactam .6 .cefamandole, moxalactam & cefoperazone may cause:

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

References

^ "Cephalosporin spectrum of resistance". Retrieved 1 July 2012.

^" cephalosporin "at ' Dorland s Medical Dictionary

^ Stork CM (2006). "Antibiotics, antifungals, and antivirals". In Nelson LH,

4) www.wikipedia.org

M. Zaharna Clin. Chem. 2009

Thanks For Your Good Attention

Designed by : Ahmed Abd El Hamid El sayed