Download 7 Intro to Antibiotic Therapy- A

7 - Anti-infective drugs
Source: Clinical Pharmacology Made Incredibly Easy! 3rd Edition
© 2009 Lippincott Williams & Wilkins
Selecting an antimicrobial drug
Selecting an appropriate antimicrobial drug to treat a specific infection involves several
important factors:
 First, the microorganism must be isolated and identified’ generally through growing a
culture.
 Then its susceptibility to various drugs must be determined. Because culture and
sensitivity results take 48 hours, treatment usually starts at assessment and then is
reevaluated when test results are obtained.
 The location of the infection must be considered. For therapy to be effective, an
adequate concentration of the antimicrobial must be delivered to the infection site.
 Lastly, the cost of the drug must be considered as well as its potential adverse
effects and the possibility of patient allergies.
Preventing pathogen resistance
The usefulness of antimicrobial drugs is limited by pathogens that may develop resistance
to a drug’s action.
Resistance is the ability of a microorganism to live and grow in the presence of an
antimicrobial drug that’s either bacteriostatic (inhibits the growth or multiplication of
bacteria) or bactericidal (kills bacteria). Resistance usually results from genetic mutation of
the microorganism.
Antibacterial drugs
Antibacterial drugs, also known as antibiotics (drugs that inhibit the growth of bacteria),
are used mainly to treat systemic (involving the whole body rather than a localized area)
bacterial infections. The antibacterials include:
 Aminoglycosides
 Penicillins
 Cephalosporins
 Tetracyclines
 lincomycin derivatives
 macrolides
 vancomycin
 carbapenems
 monobactams
 fluoroquinolones
 sulphonamides
 nitrofurantoin (nitrofuran).
The rise of the resistance movement
Indiscriminate use of antimicrobial drugs has serious consequences. Unnecessary exposure
of organisms to these drugs encourages the emergence of resistant strains, which are likely
to do far more damage than their predecessors.
Make reservations
The use of antimicrobial drugs should be reserved for patients with infections caused by
susceptible organisms and should be used in high enough doses and for an appropriate
period. New antimicrobial drugs should be reserved for severely ill patients with serious
infections that don’t respond to conventional drugs.
I.
Aminoglycosides
Aminoglycosides provide effective bactericidal activity against:
 gram -negative bacilli
 some aerobic gram -positive bacteria
 mycobacteria
 some protozoa.
Common aminoglycosides
Aminoglycosides currently in use include:
1. amikacin sulphate
2. gentamicin sulphate
3. kanamycin sulphate
4. neomycin sulphate
5. paromomycin sulphate
6. streptomycin sulphate
7. tobramycin sulfate.
Pharmacokinetics (how drugs circulate)
Because aminoglycosides are absorbed poorly from the GI tract, they’re usually given
parenterally. After I.V. or I.M. administration, aminoglycoside absorption is rapid and
complete.
Distribution
Aminoglycosides are distributed widely in extracellular fluid. They readily cross the
placental barrier, but don’t cross the blood -brain barrier.
Metabolism and excretion
Aminoglycosides aren’t metabolized. They’re excreted primarily unchanged by the kidneys.
Pharmacodynamics (how drugs act)
Aminoglycosides act as bactericidal drugs (remember, this means they kill bacteria) against
susceptible organisms by binding to the bacterium’s 30S subunit, a specific ribosome in the
microorganism, thereby interrupting protein synthesis and causing the bacterium to die.
Rising resistance
Bacterial resistance to aminoglycosides may be related to:
 failure of the drug to cross the cell membrane
 altered binding to ribosomes
 destruction of the drug by bacterial enzymes.
 Some gram -positive enterococci resist aminoglycoside transport across the cell
membrane. When penicillin is used with aminoglycoside therapy, the cell wall is altered,
allowing the aminoglycoside to penetrate the bacterial cell.
Pharmacotherapeutics (how drugs are used)
Aminoglycosides are most useful in treating:
 infections caused by gram -negative bacilli
 serious nosocomial (hospital-acquired) infections, such as gram -negative bacteremia
(abnormal presence of microorganisms in the bloodstream), peritonitis (inflammation
of the peritoneum, the membrane that lines the abdominal cavity), and pneumonia, in
critically ill patients
 urinary tract infections (UTIs) caused by enteric bacilli that are resistant to less
toxic antibiotics, such as penicillins and cephalosporins
 infections of the central nervous system (CNS) and the eye (treated with local
instillation).
Works well with others
Aminoglycosides are used in combination with penicillins to treat gram –positive organisms,
such as staphylococcal or enterococcal infections. Combination therapy increases the drugs’
effectiveness.
Warning!
Adverse reactions to aminoglycosides
Serious adverse reactions limit the use of aminoglycosides. They include:
 neuromuscular reactions, ranging from peripheral nerve toxicity to neuromuscular
blockade
 ototoxicity
 renal toxicity.
Oral history
Adverse reactions to oral aminoglycosides include:
 nausea and vomiting
 diarrhea.
Inactive duty
Aminoglycosides are inactive against anaerobic bacteria.
Role call
Individual aminoglycosides may have their own particular usefulness:
 Streptomycin is active against many strains of mycobacteria, including
Mycobacterium tuberculosis, and against the gram -positive bacteria Nocardia and
Erysipelothrix.
 Amikacin, gentamicin, and tobramycin are active against Acinetobacter, Citrobacter,
Enterobacter, Klebsiella, Proteus (indole-positive and indole -negative), Providencia,
Serratia, Escherichia coli, and Pseudomonas aeruginosa.
Drug interactions
Carbenicillin and ticarcillin reduce the effects of amikacin, gentamicin, kanamycin,
neomycin, streptomycin, and tobramycin. This is especially true if the penicillin and
aminoglycoside are mixed in the same container or I.V. line.
Drug Interaction
Amikacin, gentamicin, kanamycin, neomycin, streptomycin, and tobramycin administered
with neuromuscular blockers increase neuromuscular blockade, resulting in increased
muscle relaxation and respiratory distress.
Toxicity to the kidneys may result in renal failure; toxicity to the neurologic system
results in peripheral neuropathy with numbness and tingling of the extremities. The risk
of renal toxicity also increases when amikacin, gentamicin, kanamycin, or tobramycin is
taken with cyclosporine, amphotericin B, or acyclovir.
The symptoms of ototoxicity (damage to the ear) caused by aminoglycosides may be
masked by antiemetic drugs. Loop diuretics taken with aminoglycosides increase the risk
of ototoxicity. Hearing loss may occur in varying degrees and may be irreversible.