Download - Beta lactam antibiotic cephalosporin
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Beta Lactam AntibioticCephalosporin
Dr Lokendra Sharma Professor
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Beta Lactam Antibiotic ? Major Penicillins CephalosporinsMinor Monobactum Carbapenum
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An ideal antibiotics ?
• Broad-spectrum ? Narrow ?• Did not induce resistance• Selective toxicity, low side effects• Preserve normal microbial flora
For lecture only
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CEPHALOSPORINS ?
• Cephalosporium fungus• Dihydrothiazine ring + B lactum• Semisynthetic B-lactams derived from
chemical side chains added to 7-aminocephalosporanic acid.
• 4 generations CS add 5th• Generally more resistant to B-lactamases.
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.
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SPECTRUM1ST GENERATION gram(+). cefazolin (used as prophylactic following surgery)2ND GENERATION: gram (+) & gram (-)3RD GENERATION: good against gram (-) aerobessome cross into CNS readily e.g. cefotaxime ! used totreat meningitis4TH GENERATION: like 3rd gen but more resistant to betalactamases5th GENERATION
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Fifth Generation Ceftobiprole and ceftaroline both parentalInhibit Bind to Penicillin binding protein -2a
produce by MRSA resistance S Pneumonia
Ceftaroline 2010 for MRSA Ceftobiprole – post antibiotic effect on
MRSA
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Ceftolozane 5 GN
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??• All CEF = 1 GN (Except cefaclor 2GN)• Pi = 4 GN (CefPime, CefPirome)• ME end =3 rd generation (Exept
CefuroxiME)• ROL (CeftibipRole,CeftaRoline) 5 GN• ME,ONE,TEN (3 GN)• OR oral (CefacLOr,)• T Injectable (CefoTetan)
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. Bactericidal
Less susceptible to β-lactamases.
Disrupt the synthesis of the peptidoglycan .
The peptidoglycan layer =important structural integrity.
The final transpeptidation step in the synthesis of the peptidoglycan
Facilitated by transpeptidases known as penicillin-binding proteins (PBPs).
PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan
precursors) to crosslink the peptidoglycan.
Beta-lactam antibiotics mimic the D-Ala-D-Ala site
Irreversibly inhibiting PBP crosslinking of peptidoglycan.
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1. drugs that affect the bacterial cell wall Inhibit Transpeptidase &Carboxipeptidase
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.Pharmacokinetics
• 7 aminocephalosporinic acid = active nucleous
• New modification at position 3 & 7• Modification position 3 PK & toxicity• Modification position 7 Antibacterial
Spectrum
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.
• Conc dependent killing(CDK)= FQ,Aminog• Time dependent killing(TDK)= beta lactum• postantibiotic effects(PAE)• MIC
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Cephalosporins Antibacterial Spectrum
First Generation Second Generation Third Generation Fourth Generation
+Cocci Ө Cocci Ө Cocci Ө Cocci
Ө Bacclli Ө Bacclli Ө Bacclli Ө Bacclli
Anaerobes Anaerobes Resistance 3GN
LESS LESS LESS LESS
+ Bacclli +Cocci +Cocci
Ө Cocci + Bacclli + Bacclli +Cocci
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Cephalosporins
First Generation Second Generation Third Generation Fourth Generation
* Oral Agent
CEFADROXIL *(tissue) CEFACLOR * CEFDINIR CEFEPIME
(100% renal)
CEFAZOLIN(surgical
prophylaxis) CEFAMANDOLE CEFOPERAXONE
CEFPIROME
Cefalidin
CEFELIXIN *(bile) CEFONICID CEFOTAXIME
(prototype)
CEPHALOTHIN(prototype)
(IM pain) CEFORANIDE CEFTAZIDIME
(Thrombocytopeni)
CEPHAPRIN CEFOTETAN(anaerobics) CEFTIBUTEN
CEPHRADINE *(diarrhoea)
CEFOXITIN(prototype ) CEFTIZOXIME
CEFUROXIME
(BBB)MOXALACTAM
CEFTRIAXONE(MDR Typhoid)
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First generation cephalosporins:
CEPHALOTHIN, CEFAZOLIN, CEFALEXIN. (Streptococcus, pneumococcus but not or methicillin-resistant Staphylococcus).
+ Cocci > - Bacilli > + Bacilli > - Cocci > Anaerobics
Do not cross blood-brain barrier. Primarily excreted = kidney Ineffective Pseudomonas aeruginosa,
Enterobacter, and indole-positive Proteus species
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Second generation cephalosporins:
CEFUROXIME, CEFAMANDOLE, CEFOXITIN, CEFACLOR. - Cocci
>+ Cocci > +Bacilli - Bacilli Cefuroxime cross BBB ,Resistant to beta-
lactamase Do not achieve adequate levels in the CSF.
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Cephalosporins Third generation
cefotaxime cefixime cefpodoxime ceftazidime cefdinir Fourth generation (cefilidin,cefoselin,cefluprenam) cefe Pime cef PiromeFifth GN - CeftobipRole - ceftaRoline
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Third generation cephalosporins:
MOXALACTAM, CEFAPERAZONE, CEFTAZIDIRNE, CEFTRIAXONE.
Extended Gram negative coverage, resistant to non-Staphylococcus b-lactamase, Cross the blood-brain barrier. Enterobacter, Pseudomonas (ceftazidime and
cefaperazone only), Serratia, b-lactamase producing Haemophillus influenza and Neisseria species.
Ceftizoxime and moxalactam retain good activity against Bacteroides fragilis.
- cocci & Bacilli & Anaerobes > + Cocci & Bacilli
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Fourth generation CEFEPIME ,CEFPIROME . Comparable to third-generation but more
resistant to some beta lactamases. - Cocci & Bacilli (Resistant to 3rd Gn) & > +
Cocci & + Bacilli & Anaerobes ----NO
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Fifth Generation
CeftobipRole and ceftaRoline both parental
Inhibit Bind to Penicillin binding protein -2a produce by MRSA resistance S Pneumonia
CeftaRoline 2010 for MRSA CeftobipRole – post antibiotic effect on
MRSA
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Pharmacokinetics
Some orally most parenterally (IM or IV). widely distributed . CEFOPERAZONE, CEFOTAXIME,
CEFUROXIME, CEFTRIAXONE, AND CEFTAZIDIME (third generation) also cross the blood-brain barrier
Drugs of choice for meningitis due to Gram-negative intestinal bacteria.
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Almost all eliminated via the kidneys and actively secreted by renal tubules.
CEFAPERAZONE AND CEFTRIAXONE eliminated through biliary tract----Q.
Nephrotoxicity increase with loop diurtics …..Q
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ADVERSE EFFECTS Hypersensitivity reactions =similar
penicillins. Nephrotoxicity =CEPHALORIDINE----Q Intolerance to alcohol (disulfiram like
reaction)(Q----cefamandole, cefotetan, moxalactam, cefoperazone=MTT group)
Diarrhea= oral forms. cephaloridine ,third cefoperazone,cefixime
Superinfection. resistant organisms , fungi, often proliferate
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ADVERSE EFFECTSBLEEDING Hyperprothrombinemia= (Q-----MTT group=
cefamandole, cefotetan, moxalactam, cefoperazone)
Thrombocytopenia, Platelet dysfunction. Administration of vitamin K (10mg) twice a week can prevent this.
Neutropenia=Rare
Serum sickness=cefaclor ----- Q
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Coinfection and Superinfection ?
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CEPHALOSPORINS• Adverse reactions.
– 5-10% cross-sensitivity with pcn allergic pts.
– 1-2% hypersensitivity reactions in non-pcn allergic pts.
– Broader spectrum leads to opportunistic infections (candidiasis, C. difficile colitis).
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CEPHALOSPORINS1. Identify this manifestation ?2. What is Opportunistic infection ?3. What is the treatment and
Preventive Majors ?4. Spectrum of Bacteria ?
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Identify ?
Cause ?
Biliary sludging
syndrome ?
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USES: A cephalosporin with or without aminoglycoside 1st Trt Klebsiella pneumococci. First GN surgical prophylaxis (Cefazolin) of wound
infection. Third GN meningitis due to, meningococci, and
Haemophillus influenza. CEFTRIAXONE = TOC beta-lactamase producing
Neisseria gonorrhea. E coli (G1), Salmonella Typhoid,Parathyphoid = CEFTRIAXONE H .Ducreyi = CEFTRIAXONE Pseudo Pseudomalli = CEFTRIAXONE
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1.Antimicrobial agent acting by inhibition of cell wall synthesis isa.Erythromycinb.Tetracyclinec.Lomefloxacind.Cefepime
(d)2.Which one of the following drugs is an antipseu-domonal penicillin?
a.Cephalexinb.Cloxacillinc.Piperacillind.Dicloxacillin
(c)
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3.All of the following drugs can cause renal failure EXCEPTa.Cephaloridine b.Amphotericin Bc.Cefoperazoned.Gentamicin(c)4.Which of the following drug is NOT used for the treatment of methicillin
resistant staphylococcus aureus (MRSA)?a.Cefaclorb. Cotrimoxazolec.Ciprofloxacind.Vancomycin(a)
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5. Which of the following is a fourth generation cephalosporin?a.Ceftriaxoneb.Cefaclorc.Cefepimed.Cefuroxime(c)6. All of the following cephalosporins have good activity against pseudomonas
aeruginosa EXCEPTa.Cephadroxilb.Cefepimec.Cefoperazoned.Ceftazidime(a)7. Treatment of penicillin producing Neisseria gonorrhoeae is /area.Amoxicillinb.Ciprofloxacinc.Cefotaximed.Doxycyclinee.Azithromycin(b) (c)
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8.Which of these antibiotics are safe in renal failure?
a.Cephalexinb.Tetracyclinec.Nitrofurantiond.Gentamicine.Doxycycline
(a)
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9. Which of the following statement are true regarding cefepimea.It is a fourth generation cephalosporinb.Once a day dose is sufficientc.It possess antipseudomonal actiond.Its dose should not be reduced in renal pathologye.It is a prodrug(a)10.The mechanism of antibacterial action of cephalosporins involvesa.Inhibition of the synthesis of precursors of peptidoglycanb.Interference with the synthesis of ergosterolc.Inhibition of transpeptidation reactiond.Inhibition of beta lactamase(c)
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11.Second generation cephalosporin that can be used orally isa.Cefepimeb.Cefalothinc.Cefaclord.Cefadroxil(b)12.Third generation cephalosporin that can be given orally isa.Cefiximeb.Cefpiromec.CefaclorD.Cefadroxil(a)
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13. The antibiotic which can be given safely in a pregnant women is
a.Ciprofloxacinb.Cefuroximec.Metronidazoled.Chloramphenicol(b)14. Linezolid is best used fora.MRSAb.VRSAc,.K.pneumoniaed.E.coli(b)
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15.Which one of the following is a fourth generation cephalosporin?a.Cefuroximeb.Ceftazidimec.Cefepimed.Cefamandole(c)
16.Neutropenia is associated witha.Nafcillin b.Methicillin c.Carbencillin d.Ampicillin(a)
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17.Which of the following antimicrobials has antipseudomonal action?
(a)Cefopodoxime(b)Cephradine(c)Cefotetan(d)Cefoperazone
(d)
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18.Treatment of penicillinase producing neisseria gonarrhoeae is/are
(a)Amoxycillin (b)Ciprofloxacin(c)Cefotaxime(d)Doxycycline(e)Azithromycin(b)*(c)
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19.Which of the following antimicrobials has antipseudomonal action?
(a)Cefopodoxime(b)Cephradine(c)Cefotetan(d)Cefoperazone
(d)
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20.All are first generation cephalosporins except
a.Cefadroxilb.Cefazolinc.Cephalexind.Cefaclor D
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21.A patient develops an infection of methicillin resistant Staphylococcus aureus.All of the following can be used to treat this infection except.
a.Cotrimoxazoleb.Cefaclorc.Ciprofloxacind.Vancomycin
(b)
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22.All are true about cephalosporins,EXCEPTa.Ceftazidime is a 3rd generation cephalosporin.b.Cefoperazone has got antipseudomonal
effect.c.Cefoxitin has got no activity against
anaerobes.d.Cephalosporins act by inhibiting cell wall
synthesis.(c)
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23.Which of the following cephalosporins can be used in patients with low GFR?
a.Cefuroximeb.Cefiximec.Ceftazidime d.Cefoperazone
(d)
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24.Cephalosporin that does not require dose reduction in patient with any degree of renal impairment is
a.Cefuoxime b.Cefoperazonec.Ceftazidimed.Cefotaxime
(b)
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25.Which of the following drugs is not used for MRSA?
a.Cefaclor b.Cotrimoxazolec.Ciprofloxacind.Vancomycin
(a)
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Cephalosporin vs Penicillin
• Cephalosporin advantages– cover staphylococci– better vs. Klebsiella, enteric gram-neg. bacilli, gonococci• Cephalsporin disadvantages– cost– poor distribution to CSF (1st & 2nd gen)– not cover enterococcus
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Learning objective achieved ?
• Classification • ABS• Mechanism of Action • AE• Use
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Thank You
Dr Lokendra Sharma