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CLINICAL PHARMACOLOGY OF ANTIBACTERIAL AGENTS. Actions of antibacterial drugs on bacterial cells. Mechanisms of Action . 1. Inhibition of bacterial cell wall synthesis or activation of enzymes that disrupt bacterial cell walls (eg, penicillins, cephalosporins, vancomycin)
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Mechanisms of Action 1. Inhibition of bacterial cell wall synthesis or activation of enzymes that disrupt bacterial cell walls (eg, penicillins, cephalosporins, vancomycin) 2. Inhibition of protein synthesis by bacteria or production of abnormal bacterial proteins (eg, aminoglycosides, clindamycin, erythromycin, tetracyclines). These drugs bind irreversibly to bacterial ribosomes, intracellular structures that synthesize proteins. When antimicrobial drugs are bound to the ribosomes, bacteria cannot synthesize the proteins necessary for cell walls and other structures. 3. Disruption of microbial cell membranes (eg, antifungals) 4. Inhibition of organism reproduction by interfering with nucleic acid synthesis (eg, fluoroquinolones, rifampin, anti–acquired immunodeficiency syndrome antivirals) 5. Inhibition of cell metabolism and growth (eg, sulfonamides, trimethoprim)
Antibiotic Combination Therapy Antimicrobial drugs are often used in combination. Indications for combination therapy may include: • Infections caused by multiple microorganisms (eg, abdominal and pelvic infections) • Nosocomial infections, which may be caused by many different organisms • Serious infections in which a combination is synergistic (eg, an aminoglycoside and an antipseudomonal penicillin for pseudomonal infections) • Likely emergence of drug-resistant organisms if a single drug is used (eg, tuberculosis). Although drug combinations to prevent resistance are widely used, the only clearly effective use is for treatment of tuberculosis. • Fever or other signs of infection in clients whose immune systems are suppressed. Combinations of antibacterial plus antiviral and/or antifungal drugs may be needed
PENICILLINSIndications for Use • Clinical indications for use of penicillins include bacterial infections caused by susceptible microorganisms. As a class, penicillins usually are more effective in infections caused by gram-positive bacteria than those caused by gram-negative bacteria. However, their clinical uses vary significantly according to the subgroup or individual drug and microbial patterns of resistance. The drugs are often useful in skin/ soft tissue, respiratory, gastrointestinal, and genitourinary infections. However, the incidence of resistance among streptococci, staphylococci, and other microorganisms continues to grow.
Augmentin contains amoxicillin and clavulanate. It is available in 250-, 500-, and 875-mg tablets, each of which contains 125 mg of clavulanate.
CephalosporinsIndications for Use • Clinical indications for the use of cephalosporins include surgical prophylaxis and treatment of infections of the respiratory tract, skin and soft tissues, bones and joints, urinary tract, brain and spinal cord, and bloodstream (septicemia). In most infections with streptococci and staphylococci, penicillins are more effective and less expensive. In infections caused by methicillin-resistant S. aureus, cephalosporins are not clinically effective even if in vitro testing indicates susceptibility. Infections caused by Neiserria gonorrhoeae, once susceptible to penicillin, are now preferentially treated with a third-generation cephalosporin such as ceftriaxone. • Cefepime is indicated for use in severe infections of the lower respiratory and urinary tracts, skin and soft tissue, female reproductive tract, and infebrile neutropenic clients. It may be used as monotherapy for all infections caused by susceptible organisms except P. aeruginosa; a combination of drugs should be used for serious pseudomonal infections.
Aminoglycosides Contraindications to Use • Aminoglycosides are contraindicated in infections for which less toxic drugs are effective. The drugs are nephrotoxic and ototoxic and must be used very cautiously in the presence of renal impairment. Dosages are adjusted according to serum drug levels and creatinine clearance. The drugs must also be used cautiously in clients with myasthenia gravis and other neuromuscular disorders because muscle weakness may be increased.
