Beta lactam antibiotics & other cell wall synthesis inhibitors

3.  Major antibiotics – inhibits bacterial cell wall synthesis
 Penicillins – derivatives of 6- aminopenicillinic acid
 Beta lactum ring essential for antibacterial activity

5.  PKs; vary in their resistance to gastric acid & oral
bioavailability
 Amoxicillin – Absorption is impaired by food. 1- 2 hours
before food
 Polar compounds, unmetabolised, gets filtered in urine
 Naficillin – gastric irritant, given by injection, bile, highly
protein bound
 Parenteral formulations; benzylpenicillin,ampicillin,
piperacillin, ticarcillin
 T1/2 30min – one hour
 Crosses BBB - Meninigitis

6.  Penicillin binding proteins located in the bacterial cytoplasmic
membrane
 Inhibition of the transpeptidation reaction that crosslinks
linear peptidoglycan chain of cell wall
 + autolytic enzymes
 Resistance; beta- lactamases = staphylococci & gram
negative organisms
 PBPS- structural change (PRSP, streptococcus pneumonia)
 Porins – inhibits entry of penicillin in pseudomonas
aeruginosa

10.  Derived – penicillium molds
 M.o.a; cell wall inhibition, osmotic rupture
 Time dependent bacterial killing
 PKs; destroyed in stomach
 Can cross inflammed meninges
 T1/2 < 2hr
 Renal, probenicid

12. Uses
 Streptococcus pneumonia
 Neisseria meningititis, septicaemia
 Anthrax
 Gas gangrene
 Tetani
 Diphtheria
 Syphilis
 Endocarditis
 Rheumatic fever
 Lyme, gonorrhea (resistant)

13.  A/E; allergic reactions, itching, rashes, fever & angioedema –
IgE Abs
 Supra infection; diarrhea - clostridium difficle
 Neutropenia, hemolytic anemia, thrombocytopoenia, interstitial
nephritis
 Sodium/potassium salts – renal/cardiac disease
 Co- amoxiclav – hepatic toxicity

14. penicillins uses
Narrow – spectrum, penicillinase susceptible agents:
Penicillin G(acid stable) & V
Gram –ve,+ ve cocci, Gm +ve bacilli,
spirochetes
Very –narrow spectrum penicillinase – resistant drugs:
Methicillin, nafcillin, oxacillin
Penicillinase producing staphylococci
Flucloxacillin – cholestatic jaundice > 55
yrs
Wider – spectrum penicillinase susceptible drugs:
Ampicillin 500mg – 4-6 hrly
Deposits in bile & amoxicillin (250 mg –
8hr)
UTI, Sinusitis,otitis & LRTI,Same as Penicicillin
G, more Gm –ve coverage – enterococci,
L.monocytogenes, E.coli,P mirabilis, H influenza,
M. catarrhalis
Anti- pseudomonal drugs:
Ticarcillin+ clavulinic acid
Piperacillin+ tazobactum
carbenicillin
Pseudomonas aeruginosa
Ureidopenicillins – septicaemia

15.  Hypersensitivity (skin testing) – anaphylactic shock, serum
sickness (urticarial, fever, joint swelling, angioneurotic
oedema, intense pruritus)
 Fever, interstitial nephritis ( autoimmune rxn to penicillin –
protein complex)
 Eosiniphilia, hemolytic anemia
 Renal failure – Seizures
 Large doses – nausea,vomiting, GI upset
 Skin rashes (macular rashes) – viral illness

17.  Gm+ve, gm-ve cocci, streptococci & staphylococci
 PKs; variably absorbed, renal excretion (probenicid)
 Clinical uses; soft tissueabscess & cellulitis
 Cefazolin – surgical prophylaxis
 Alternative for penicillin causing mild allergic reactions

18.  First generaion Gm+ve, extended gm-ve coverage
 Clinical uses; β- lactamase producing H influenzae, Moraxella
 Sinusitis, otitis, LRTI
 Anaerobic infections – peritonitis, diverticulitis & PID
 Community acquired pneumonia - H influenzae, klebsiella
 Cefuroxime crosses BBB (Less effective in meningititis)

19.  Extended gm-ve coverage & BBB
 Citrobacter, serratia, providencia, β-lactamase producing
 H influenzae, Neisseria, Pseudomonas, Bacteroid fragilis
 Ceftriaxone & cefotaxime – PRSP
 Ceftriaxone & cefixime (oral) – gonorrhea
 Ceftriaxone – otitis media single injection

20.  Cefipime – resistant to β-lactamase producing gm-ve m-os
 Enterobacter, H influenzae, Neisseria, PRSP
 Ceftaroline – MR Staphylococci

21.  Toxicity: skin rashes to anaphylactic shock, nephritis,
granulocytopoenia, hemolytic anemia
 Cross hypersensitivity
 Others; thrombophlebitis, renal toxicity – interstitial
nephritis & tubular necrosis
 Disulfiram like reactions
 Methylthiotetrazole – bleeding disorder (vitamin K)

22.  Aerobic gm-ve rods
 Sructural similiraties with ceftazidime
 Penetrates into CSF
 T1/2 – 1-2 hrs
 Cautious in renal failure
 Penicillin allergic patients tolerate aztreonam
 Uses- pneumonia,meningititis, sepsis, lower UTI
 A/E ; GI upset,hepatotoxicity, superinfection, vertigo &
headache, cross allergenicity

23.  Available as fixed combinations with penicillins
 Ampicillin+ sulbactam – β – lactamase producing
staphylococcus aureus & Hinfluenzae
 Piperacillin + tazobactam – pseudomonas
 Uses- empirical therapy for infections in both
immunocompromised & immunocompetent patients,
treatment of mixed aerobic & anaerobic infections - intra-
abdominal infections
 Dose adjuzments – Renal failure

24.  Gm-ve rods (pseudomonas aeruginosa), gm+ve,
anaerobes
 Imipenem inactivated – dihydropeptidases in renal tubules
– low urine concentrations
 Cilastatin – renal dehydropeptidase
 PKs – penetrate body tissue, fluids well, CSF
 Dose reduction – renal failure patients
 uses: PRSP, Penicillinase producing bacteria,
enterobacter
 A/E: NAUSEA, Seizures in renal failure

25.  Streptococcus orientali, Amycolatopsis orientalis
 M.o.a: binds to terminal D- ala-D-ala – inhibits cellwall
synthesis
 Resistance – modification of D- ala-D-ala site
 Antibacterial activity – gm +ve bacteria
 Synergistic activity with streptomycin & gentamicin –
enterococcus, linezolid, rifampicin better results
 Clostridium difficle – anaerobe
 PKs; poor GI absorbption – helps in C.difficle treatment
 Can penetrate CSF – Inflammed meninges
 Glomerular filtration – half life prolongs in renal complications
patients & hemodialysis

26. Clinical Uses
 Parenteral – endocarditis – MRSA
 Meningitis – PRPneumococcus
 A/E; Tinnitus, deafness, nephrotoxicity cautious while aminoglycosides
used
 Phlebitis
 Red man syndrome – histamine
 Rx - diphenhydramine