CLINICAL PHARMACOLOGY OF ANTIBACTERIAL AGENTS

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CLINICAL PHARMACOLOGY OF ANTIBACTERIAL AGENTS
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Actions of antibacterial drugs on bacterial cells
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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, antiacquired
  immunodeficiency syndrome antivirals)
• 5. Inhibition of cell metabolism and growth (eg,
  sulfonamides, trimethoprim)

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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

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PENICILLINS Indications 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.

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Aminopenicillins
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Piperacillin
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Augmentin contains amoxicillin and clavulanate.
It is available in 250-, 500-, and 875-mg
tablets, each of which contains 125 mg of
clavulanate.
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MACROLIDES
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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.

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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.

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Lincosamindes
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• Antibiotic resistance

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FLUOROQUINOLONES
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ANTIVIRAL DRUGS
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Drugs for HIV Infection and AIDS(Antiretrovirals)
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Antifungal Drug Mechanisms
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