N509 Pharmacology

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Infection:

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Invasion and multiplication of microorganisms in body tissue, which may result in local cellular injury

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Classification of Infections:

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1.Community Acquired

2.Nosocomial

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Classification of Microorganisms

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bacteria
fungus
virus
paracite

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Classification of Antibiotic Use

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1.Prophylaxis
2.Empiric
3.Culture Documented
Colonization vs infection
Contaminant vs infectious pathogen

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Classification of Antibiotics

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Antimicrobia
Spectrum of Activity
Mechanism of Action
a.Inhibition of bacterial cell wall synthesis
b.Alteration in cell membrane function
c.Inhibition of protein synthesis
d.Interference of nucleic acid metabolism
e.Interference with intermediate cell metabolism

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Factors Affecting the Choice of Antibiotic

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1.Empiric Antibiotic Selection
2.Therapy Beyond Empiric Therapy

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Empiric Antibiotic Selection

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a.signs and symptoms
b.suspected site of infection
c.suspected causative organism
d.antibiotic susceptibilities
e.prior antibiotic usage
f.patient allergies
g.cost
h.patient age
i.renal or hepatic insufficiency
j.pregnancy or lactation

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Therapy Beyond Empiric Therapy

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a.gram stain
b.culture and susceptibility results
c.patient’s sign and symptoms

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BETA-LACTAM ANTIBIOTICS

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Penicillins
Beta Lactamase Inhibitors: (clavulanic acid, sulbactam, tazobactam)
Cephalosporins
Carbapenems

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Penicillins

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MOA: binds to specific penicillin binding proteins (PBP) and inhibits cell wall synthesis

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Mechanism of resistance

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a.bacterial production of an enzyme (penicillinase/beta lactamase) which cleaves the beta lactam ring inactivating the drug
frequently seen with Staphylococcus aureus

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Natural penicillins (Penicillin G, Penicillin V):

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respiratory tract infections, gonorrhea (no longer drug of choice), syphilis, pneumococcal pneumonia, aspiration pneumonia (community acquired), meningitis due to susceptible organisms

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Penicillinase resistant penicillins (Dicloxacillin, Oxacillin, Cloxacillin, Methcillin, Nafcillin):

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infections due to Staphylococcus spp., skin and skin structure infections

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Aminopenicillins (Ampicillin, Amoxicillin, Becampacillin, Hetacillin):

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UTI, respiratory tract infections, ear infections, pneumonia, meningitis due to susceptible organisms

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Extended spectrum penicillins:

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various infections involving gram negative bacteria or mixed gram negative aerobic/anaerobic infections e.g., intra abdominal infections, pelvic infections, pneumonia
- Carboxypenicillins (Carbenicillin, Ticarcillin)
- Ureidopenicillins (Azlocillin, Mezlocillin, Pipercillin)

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Adverse Effects of pennicillans

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hypersensitivity reactions
GI: nausea, vomiting, diarrhea
phlebitis: local irritation at the IV site
seizures
hematologic
superinfection with Candida spp.

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pennicillan Drug Interactions

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tetracycline, chloramphenicol
Uricosuric agents
aminoglycosides
oral contraceptives:

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Beta Lactamase Inhibitors:

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clavulanic acid, sulbactam, tazobactam

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Beta Lactamase Inhibitors: MOA

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Agents which have little or no antibacterial activity but bind to beta lactamase (penicillinase)

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Cephalosporins

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Mechanism of Action: same as penicillins
MOR: bacterial production of beta lactamase which may cleave the beta lactam ring OR may bind to the drug preventing its access to target proteins

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1st generation cephalosporins (FGC)

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Cefazolin
Cephalexin*
Cefadroxil
-good activity against gram positive organisms
-good activity against E. coli, K. pneumoniae, and P. mirabilis but less active against other gram negative organisms

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2nd generation cephalosporins (SGC)

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Cefpodoxime*
Cefuroxime
Cefuroxime axetil*
Cefaclor*
Cefprozil*
Loracarbef*
Defdinir
anti anaerobic-Cefoxitin,Cefotetan

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2nd generation cephalosporins (SGC) activity

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1)good activity against gram positive organisms but less active than 1st generation cephalosporins
2)good activity against gram negative organisms covered by FGC plus H. influenzae, but less active than 3rd generation cephalosporins
3)active against a variety of anaerobic bacteria including B. fragilis (cefoxitin and cefotetan only)

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3rd generation cephalosporins (TGC)

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Cefotaxime
Ceftriaxone
Ceftizoxime
Cefoperazone
Cefixime*
Ceftibuten*
Anti pseudomonas:
Ceftazidime
1)some activity against gram positive organisms but less active than 1st and 2nd generation cephalosporins
2)very active against a wide variety of gram negative bacteria including Enterobacter, Serratia, and other species generally resistant to FGC and SGC
3)activity against P. aeruginosa (cefoperazone and ceftazidime only)

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4th generation cephalosporins

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Cefepime
1)good activity against gram positive organisms; exception: methicillin resistant Staph. aureus and methicillin-resistant Staph. epidermidis, enterococcus
2)very active against a wide variety of gram negative bacteria including Enterobacter, Serratia, and other species generally resistant to FGC and SGC
3)activity against P. aeruginosa

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BBB

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only 3rd generation cephalosporins and cefuroxime can penetrate the cerebrospinal fluid (better penetration with inflamed meninges)

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FGC treatment of

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staphylococcal and streptococcal infections in penicillin-allergic patients, otitis media, urinary tract, respiratory tract, skin and soft tissue infections

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SGC treatment of

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respiratory tract infections involving beta lactamase producing H. influenzae, skin and soft tissue, urinary tract, CNS (cefuroxime only), and abdominal infections

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TGC treatment of

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lower respiratory tract, skin and skin structure, complicated or uncomplicated urinary tract, gynecologic, intra abdominal, and bone and joint infections, CNS infections (not cefoperazone and cefixime)

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Carbapenems

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Imipenem/Cilastatin (Primaxin®) and Meropenem (Merrem®)
Ertapenem (Invanz®)

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Ertapenem (Invanz®)

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Mechanism of Action: bactericidal
Resistant to most beta lactamases
broad spectrum

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Imipenem/Cilastatin (Primaxin®) and Meropenem (Merrem®)

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bactericidal
Resistant to most beta lactamases
very broad spectrum

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Aztreonam (Azactam®): monobactam

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similar to beta lactams
No activity against gram positive or anaerobic bacteria