Antimicrobial Pharmacology - NCLEX-PN

Macrolides, streptogramins, and clindamycin all work by inhibition of the 50S subunit of bacterial ribosomes. Tetracyclines have a similar mechanism of action, but instead affect the 30S unit of bacterial ribosomes.

Polymyxin antibiotics function by interfering with phospholipid function in bacterial cell membranes. After binding to lipopolysaccharide (LPS) in the outer membrane, polymyxins' hydrophobic tail causes damage to both the inner and outer membranes of Gram-negative bacteria.

Rifampin inhibits bacterial RNA synthesis by inhibiting RNA polymerase. This prevents the transcription of proteins within the bacterial cell, leading to cell death.

Hepatotoxicity and potential liver failure are the most serious potential adverse effects of rifampin use. Patients on this medication must establish baseline liver function tests and be monitored for liver damage. None of the other conditions listed are associated with rifampin use.

Aminoglycoside antibiotics are used to treat Gram negative bacteria. They have not been shown to be effective against Gram positive bacteria and are not antifungal. Recall the major difference between the Gram negative and positive bacteria are their cell wall composition; Gram negative have a small proportion of peptidoglycan and a high proportion of lipopolysaccharide, while Gram negative bacteria have a large proportion of peptidoglycan.

The only aminoglycoside antibiotic among those listed is streptomycin. Other examples of aminoglycosides include tobramycin and gentamicin. All aminoglycosides either end in -mycin or -micin. However, this suffix is not exclusive to aminoglycosides. It is also seen in the macrolides: erythromycin and azithromycin and both macrolides, and in lincosamides such as clindamycin.

Aminoglycoside antibiotics such as streptomycin and gentamicin have been associated with vestibular toxicity and hearing loss. Aminoglycosides remain in inner ear fluids longer than serum and can have a latent ototoxic effect, causing hearing loss even after the antibiotic has been discontinued. None of the other antibiotics listed are associated with ototoxicity.

Ciprofloxacin belongs to the fluoroquinolone class of antibiotics. Other antibiotics in this class include norfloxacin, levofloxacin, and nadifloxacin.

Fluoroquinolones (the most commonly prescribed of which is ciprofloxacin) carry a risk of all of the following adverse effects: sudden tendon rupture or tendonitis, hepatotoxicity or liver failure, seizures, and permanent peripheral neuropathy. Other adverse effects include C_lostridium difficile_ associated diarrhea, bone marrow suppression, Steven-Johnson's Syndrome, tremors, and psychosis. The majority of these adverse effects are seen in higher numbers in children and the elderly.

Tetracycline antibiotics are contraindicated in pregnant women and small children due to their tendency to irreversibly stain developing teeth. They can also affect fetal bone growth and so are pregnancy category D (known incidence and risk of fetal harm).

Of the antibiotics listed, amoxicillin is the only one considered safe in pregnancy. Doxycycline and gentamicin are both pregnancy category D (known to cause fetal harm). Levofloxacin is category C (fetal harm can not be ruled out).

All of the drugs listed frequently cause C_. difficile_ overgrowth and C_. difficile_ associated diarrhea except vancomycin, which is often used as a treatment for persistent C_. difficile_ infections.

Penicillins belong to a larger class of antibiotics known as beta-lactams. These antibiotics inhibit cell-wall synthesis and are exclusively used to treat Gram positive bacteria. They are not effective against Gram negative bacteria or fungi.

Fluoroquinolones are considered to be the treatment of choice for E . coli infections due to their effectiveness in relieving diarrhea and minimal serious adverse effects. Aminoglycosides and beta-lactam antibiotics may also be effective, as a second choice.

Gentamycin, an antibiotic and aminoglycoside, inhibits protein synthesis of gram-negative bacteria. It treats severe systemic infections. It may cause ototoxicity and nephrotoxicity, as well as anorexia, nausea, vomiting, and diarrhea. Diaphoresis is not a common side effect of gentamycin.

The correct answer is "inhibition of topoisomerase II," as this is the mechanism of action of fluoroquinolone antibiotics, such as levofloxacin.

The other choices are incorrect for the following reasons:

Blockage of tRNA-ribosome-mRNA complex binding is the mechanism of action of tetracycline antibiotics.

Disruption of mycolic acid synthesis is the mechanism of action of various anti-fungal agents.

Disruption of peptidoglycan cross-linkage is the mechanism of action of vancomycin.

Inhibition of peptidoglycan synthesis is the mechanism of action of beta-lactam antibiotics.

Vancomycin is the correct answer. Antibiotics that inhibit bacterial cell wall synthesis include the beta-lactam antibiotics (penicillins and cephalosporins), vancomycin, and bacitracin. Synthesis of the bacterial cell wall takes place in 4 steps: 1) Precursors of the cell wall are synthesized within the bacterial cytoplasm. 2) The precursors are transported across the cell membrane. 3) Outside the cell membrane, the precursors are linked together to form chains called peptidoglycans. 4) The peptidoglycan chains are cross-linked to form a rigid, stable cell wall.

• Beta-lactam antibiotics act by inhibiting step 4, the cross-linking of peptidoglycans. They also activate hydrolytic enzymes, which degrade already-existing cell walls. This usually results in lysis and death of the bacteria. (Mutant bacterial strains, which lack the hydrolytic enzyme, are not killed by beta-lactams, but their growth is arrested)
• Vancomycin inhibits step 3, the elongation of the peptidoglycan chains
• Bacitracin interferes with step 2, the transport of precursors across the cell membrane

Aminoglycosides, tetracyclines, macrolides (erythromycin and its relatives), clindamycin, and chloramphenicol are inhibitors of bacterial protein synthesis. They act by binding to ribosomal subunits.

• Aminoglycosides bind to several sites on the bacterial ribosome. They interfere with the movement of ribosomes along the strand of mRNA. They also induce misreading of the mRNA so that incorrect amino acids are incorporated into the elongating peptide chain
• Tetracyclines bind to the 30S ribosomal subunit. Macrolides, clindamycin, and chloramphenicol bind to the 50S subunit. These antibiotics interfere with the attachment of tRNA to the ribosome, thus preventing the addition of amino acids to the peptide chain

Sulfonamides and trimethoprim act by inhibiting the synthesis of folic acid. Certain bacteria synthesize folic acid from precursors by a series of enzyme-catalyzed reactions. Sulfonamides and trimethoprim block different steps in this synthetic pathway by binding competitively to different enzymes. When used together, their actions are synergistic (mammals do not synthesize folic acid, but require it as a vitamin; therefore, these drugs do not interfere with metabolism in mammalian cells).

Quinolones (e.g. norfloxacin and ciprofloxacin) inhibit bacterial nucleic acid synthesis by interfering with DNA gyrase, a bacterial enzyme that catalyzes supercoiling of DNA.

Polymyxins have a detergent action that disrupts bacterial cell membranes. They can also have the same toxic effect on mammalian cells; for this reason, they are seldom used except in topical preparations.

Initial treatment for pulmonary or extrapulmonary tuberculosis is isoniazid (INH), rifampin (RMP), and pyrazinamide (PZA) as a short-course intensive daily regimen for 2 months, followed by INH and RMP for 4 more months. The most common side effects of rifampin are reddish urine and stool, saliva, sweat, tears, diarrhea, joint pain, back pain, swelling of feet and/or legs, and blood in urine. Hyperuricemia is a major toxic effect of pyrazinamide; other toxic effects include fever, indigestion, urticaria, photosensitivity, and joint pain. Isoniazid can cause polyneuropathy, jaundice, muscle pain, confusion, and unsteady walk.

The tetracycline antibiotics possess a wide range of antimicrobial activity against gram-positive and gram-negative bacteria, as well as Rickettsia, Mycoplasma, Chlamydia, Ureaplasma, some atypical mycobacteria, and amoebae. These drugs are primarily bacteriostatic and act by inhibiting microbial protein synthesis. The tetracyclines, after active transport into the cell, bind to the 30 S ribosomal subunit. This prevents the access of aminoacyl tRNA to the acceptor site on the mRNA-ribosome complex, inhibiting the addition of amino acids to the growing peptide chain. This effect is, for the most part, reversible and removal of the drug results in loss of action.

The other mechanisms listed are utilized by other antimicrobial agents. For example, all beta-lactam drugs are selective inhibitors of cell wall synthesis, and therefore active against growing bacteria. Sulfonamides are structural analogs of PABA that is necessary for folic acid synthesis. By competitive inhibition, the drug interferes with folic acid synthesis. Folic acid is an important precursor to the synthesis of nucleic acids. Quinolones are examples of antibiotics which inhibit bacterial DNA synthesis by blocking of the DNA gyrase. Antibiotics—polymyxin and colistin—and the antifungal agent amphotericin B act by inhibiting cell membrane function.