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6.2 Antibiotics
Lecturer: Nico Fabian
III. Pharmaceutical Microbiology: Antibiotics Food retards transit (↓abs) except Amoxicillin
- product of microorganisms or chemical synthesis Poor penetration in eyes, prostate, & CNS
- Inhibit other organisms even in small quantities
o BACTERIOSTATIC- retard growth o Excretion via the kidneys
o BACTERICIDAL- kill ALL Probenecid ↓tubular secretion of penicillin ↑penicillin;
o RESISTANCE: no response to antibiotic hence ↓dose of penicillin
o SUPERINFECTION: e.g Clostridium difficile - PENICILLINS
- TB MDR XDR 1. Natural penicillin
o 1stline 2nd line trial and error; gen. or broad spectrum - Susceptible to β-lactamase
o May be bacterial, viral 2.1 Penicillin G/ benzylpenicillin
o Complication: meningitis - Acid-labile; IV
- G(+,-), spirochete, anaerobe (eg. Clostridium), x Bacillus
A. CELL WALL SYNTHESIS INHIBITORS - Depot formulations; aqueous
- MOA: (-) Transpeptidation Benzathine Pen G (IM)
- Hx: Alexander Fleming I: syphilis; prophylaxis for rheumatic
o Discovered penicillin by serendipity heart fever
o Isolated by Florey and co-workers Procaine Pen G (IM): procaine ~ local anesthetic
- β-lactam ring 1.2 Penicillin V/ phenoxymethylpenicillin
- Acid stable; PO
2. β-lactamase resistant/ anti-staphylococcal penicillins
- active against Staphylococci & other G(+)
- disadv: not for G(-)
2.1 Methicillin
- Nephrotoxic (out of the market)
- MRSA (methicillin-resistant Staphylococcus aureus) &
MRSE (methicillin-resistant Staphylococcus epidermidis)
o bactericidal activity & antigenic determinant VANCOMYCIN
o penicillin beta-lactamase penicilloic acid 2.2 Oxacillin
- Stability - I: soft tissue infections
o In crystalline/ powder form 2.3 Nafcillin
o Solutions/ suspensions are freshly prepared 3. Extended-spectrum
o Stored in amber bottles - G(+), improved G(-) activity; susceptible to β-lactamase
- Special precautions 3.1 Aminopenicillin
o All penicillins are cross-sensitive w/ cephalosporins (5-16% cross- - x Klebsiella, enterobacter, pseudomonas, serratia, proteus
sensitizing) - cause morbilliform rashes
- Pregnancy category B - Ampicillin
- Drug-drug interactions Prototype; lowest BA
o Allopurinol + ampicillin rash (+) Sulbactam Unasyn®
o Penicillin + bacteriostatic ↓bactericidal act., antagonistic S/E: pseudomembranous colitis
o Penicillin + β-blocker anaphylaxis - Bacampicillin
Physiologic Histamine antagonist: epinephrine
prodrug; highest BA
- Pharmacokinetics - Amoxicillin
o Absorption varied except in acid-labile like Pen G, Methicillin
MODULE 6 RAMON CORTEZA III 1OF6
Module 6.2 Antibiotics
Absorption not affected by food
(+) K Clavulanate Co-amoxiclav (Augmentin®)
S/E: rash o
3.2 Anti-pseudomonals ANAEROBIC ACTIVITY
- Serious infections caused by G(-) 2ND GEN 3RD GEN
- Active against Pseudomonals, Klebsiella Cefoxitin Cefotaxime
- Synergistic when used with Aminoglycosides Cefotetan Ceftriaxone
- Combined w/ β-lactamase inh. Ceftizoxime
Resemble β-lactam suicide inh.
Potentiation o
- Carboxypenicillins Ceph Except - Staph and Strep
1st gen
Carbenicillin Cefadroxil
Ticarcillin: (+) clavulanate Timentin® Cefazolin
- Ureidopenicillins
Mezlopenicillin Cef-vowel Cefmetazole - Community-acquired pneumonia (CAP)
Piperacillin: (+) tazobactam Piptaz®, Zosyn® Cefprozil - Crosses BBB
2nd
Azlocillin Loracarbef - activity against gram + and gram – (including
- CEPHALOSPORINS Haemophilus, Klebsiella, Proteus, E.coli
o ↑generation ~ ↑G(-) act; bactericidal - x act. vs Pseudomonas
o Greater efficacy against resistant microorganisms Cef- Cefixime - Crosses BBB (except ceftibuten,
o Stable vs β-lactamase consonant Cefotaxime cefpodoxime, cefixime, cefoperazone): can
o No act. vs enterococci & listeria Cefoperazone be used for meningitis
3rd
o Special precautions Moxalactam - x reliable vs. enterobacter: x UTI (e.coli)
Pseudomembranous colitis Proxetil - Ceftazidime, Cefoperazone: Pseudomonas
Coagulation abnormality: compromise CF formation - Ceftriaxone: lyme, gonorrhea
Nephrotoxic - Pseudomonas
Preg. Cat. B Cefepime - Atypical organism
4th
Pharmacokinetics Cefpirome - MRSA
i. Well-absorbed in GIT (PO) - Enterobacter
ii. Absorption delayed by food but amount absorbed is Ceftobiprole - MRSA, pseudomonas
5th
unaffected Ceftaroline - MRSA
Drug Interactions
i. (+) aminoglycosides severe nephrotoxicity - OTHER β-LACTAMS
ii. (+) anticoagulants ↑risk hyperprothrombinemia 3.1 Monobactams
iii. (+) probenecid ↑cephalosporin plasma level - active against G(-)
iv. Alcohol + 2nd/3rd gen Disulfiram(Antabuse®) effect; - Aztreonam
*disulfiram inh aldehyde dehydrogenase
Chromobacterium violaceum
acetaldehyde A/E
Weakly immunogenic, resistant to β-lactamase
o
Reserved for very serious infection
Gram (+) Gram (-)
3.2 Carbapenems
1st +++ +
- Share allergic potential w/ penicillin
2nd ++ ++ - Imipenem
3rd + +++ G(+,-), anaerobe
MODULE 6 RAMON CORTEZA III 2OF6
Module 6.2 Antibiotics
Inh by dehydropeptidases in renal tubules - 30 s
(+) Cilastatin w/c inh renal dehydropeptidase - Bactericidal, only for g(-), not preferred for (+) & anaerobes
- Meropenem - More active in alkaline pH
More g(-) but less g(+) than imipenem - SToKeNeomycin (Streptomyces)
3.3 Glycopeptide o Streptomycin
- Vancomycin o Tobramycin
Streptococcus orientalis; g(+) o Kanamycin
DOC: MRSA (VRSA Daptomycin) o Neomycin
MOA: alter RNA synthesis (sim. to rifampicin) - SNAGmicin (Micromonospora)
A/E: Redman/ Redneck syndrome o Sisomicin
If rapid infusion o Netilmicin
- BACITRACIN o Amikacin
- Bacillus subtilis, g(+) act. o Gentamicin
- Topical use since nephrotoxic
- Special precautions
B. PROTEIN SYNTHESIS INHIBITORS o Narrow TI
- Buy AT 30, CEL at 50 o No significant level in CSF, eyes
1. Tetracycline - A/E
- Absorption impaired by food except DOXYCYCLINE, MINOCYCLINE o Nephrotoxicity
- Interacts w/ milk, Al3+, Ca2+, Mg2+, Fe2+ (chelation) Neomycin
- Lipid solubility: high for Doxycycline & minocycline Gentamicin
o *LUNA (lipophilic, unionized, non-polar Absorbed) Tobramycin
- G(+), (-), anaerobe, atypical organism (mycoplasma, chlamydia, o Vestibular toxicity
legionella, pneumophila) Streptomycin
- I: cholera, malignant pleural effusion gentamicin
- Warnings o Ototoxicity
o Photosensitivity : demeclocycline Neomycin
o Hepatotoxicity Amikacin
o nephrotoxicity Kanamycin
- Doxycycline - Interactions
Choice for px w/ preexisting renal conditions since it is not o (+) cephalosporins nephrotoxicity
excreted renally o (+) neuromuscular blockers(eg Tubocurarine) paralysis
Prophylaxis for leptospirosis, lyme disease, anthrax 2. Macrolides
- Minocycline - G(+), (-), anaerobes
Penetrate saliva - Penetrate pleural fluid, CSF if meninges are inflamed
- Most common A/E: GIT upset
Theoretically used for meningococcemia but used for
- Erythromycin
pimple tx nowadays
- Tigecycline Aka Ilotycin; from Streptomyces erythreus
G (+) Prototype, natural macrolide
For skin & intraabdominal infection Best prep: erythromycin estolate
- Demeclocycline DOC: chlamydia, corynebacterium, CAP (Streptococcus
Syndrome of inappropriate ADH secretion (SIADH) pneumoniae)
2. Aminoglycosides 1% used as prophylaxis for ophthalmia neonatorum
a. Dapsone
- Structural analog of sulfonamides
- MOA: inh folate synthesis
- Other ind: Pneumocystis carinii pneumonia (HIV px)
- A/E
Hemolysis in G6PD px
“Sulfone syndrome”: exfoliative dermatitis
Exfoliation also present in S. aureus
scalded skin syndrome
b. Rifampicin
c. Clofazimine
- Sulfone-resistant
- A/E: skin discoloration