Antimicrobial Agents

1. Antimicrobial Agents Kristina Lilly

2. Overview • Antimicrobial - Include both natural and synthetic compounds that either inhibit or kill microorganisms • Tobramycin • Aztreonam

3. Tobramycin • TRADE NAME: Tobi, ak-tob, nebcin, nebcinped, tobrex • CLASSIFICATION: Aminoglycoside, Antibiotic • CONCENTRATION AND DOSE: 300 mg/5 ml ampoule; Adults and children≥6 yr: 300 mg bid, 28 days on/28 days off the drug • MODE OF ACTION: Aminoglycosides bind irreversibly to the 30S bacterial ribosome and inhibit the translation of ribonucleic acid (RNA) into proteins. Aminoglycosides also competitively displace cations that link lipopolysaccharides in the outer cell wall of gram-negative bacteria. This destabilization of the cell wall results in increased cell permeability and lysis. Aminoglycosides are bactericidal agents and demonstrate concentration-dependent killing. They are often synergistic when used in combination with β-lactam antibiotics.

4. Tobramycin Continued • THERAPEUTIC USES: Interferes with protein synthesis of susceptible microorganisms, treats lung infection (SVN); Pseudomonas aeruginosa in C; streptococci, Staphylococcus aureus, Corynebacterium spp., penicillin-susceptible Streptococcus • CONTRAINDICATIONS: Hypersensitivity to tobramycin • SIDE EFFECTS: IM: pain IV: phlebitis, thrombophlebitis; The primary toxicities associated with the use of aminoglycosides are nephrotoxicity and ototoxicity. • ADVERSE REACTIONS and PRECAUTIONS:. • Common symptoms associated with the development of cochleotoxicity include tinnitus (ringing in the ears); vestibular toxicity manifests as dizziness and nausea. • Another serious but rare toxicity is neuromuscular blockade associated with peritoneal irrigation and rapid high-dose aminoglycoside use. Underlying conditions such as myasthenia gravis or concomitant use of neuromuscular blockers may potentiate this side effect, requiring supportive measures such as intubation and possible ventilation support

5. Aztreonam • TRADE NAME: Cayston • CLASSIFICATION: Monobactum, synthetic bactericidal antibiotic; Aztreonamis a synthetic monocyclic β-lactam antibiotic. This is the only commercially available agent belonging to the class of antibiotics known as the monobactams. • MODE OF ACTION: Aztreonam has a mechanism of action similar to that of other β-lactam antibiotics and demonstrates bactericidal activity. • ROUTE OF ADMINISTRATION: Inhalation, Injection

6. Aztreonam Continued • THERAPEUTIC USES: Aztreonam is active only against gram-negative aerobic bacilli (most Enterobacteriaceae and P. aeruginosa). It is not effective against gram-positive and anaerobic bacteria. The strict gram-negative spectrum of aztreonam limits its use as a single agent. It has been used for the treatment of serious urinary tract infections and bacteremia. Aztreonam has more extensive use in combination therapy for treatment of intraabdominal infections, spontaneous bacterial peritonitis, gram-negative osteomyelitis, and hospital-acquired pneumonia and in patients with neutropenic fever. • SIDE EFFECTS: Rare cases of rashes and even anaphylactic reactions have been reported when aztreonam was used in patients with a β-lactam allergy. • PRECAUTIONS: Aztreonam is well tolerated and is thought to have little to no cross-reactivity to β-lactams.

7. Reference: Chapter 14: Antimicrobial Agents Gardenhire, Douglas S.. Rau's Respiratory Care Pharmacology, 7th Edition. Mosby, 112007. <vbk:978-0-323-03202-5#outline(16)>.