Editing Infections: Antibiotics (section)

==Principles of Antibiotic Therapy==
*Factors to consider when selecting
**Empirical therapy include whether the infection is complicated or uncomplicated, spectrum of activity of the drug against the probable pathogen, history of hypersensitivity, potential side effects, and cost
**Duration of therapy include the extent and duration of tissue invasion, bacterial concentration in urine, achievable urine concentration of the antimicrobial agent, and risk factors that impair the host and natural defense mechanisms
*'''<span style="color:#ff0000">Antimicrobials are excreted in a concentrated form compared to their serum concentrations'''
**Resolution of infection is associated with the susceptibility of the bacteria to the concentration of the antimicrobial agent in the urine.
**'''Susceptibility testing is based on concentrations obtained in the serum'''
***'''Some antibiotics do not achieve adequate serum concentration levels to be considered effective for bacteriemia, but could be effective at its achievable urinary concentration.'''
****For example, E. Coli susceptible testing may show resistance to amoxicillin, even though amoxicillin may actually be effective for urinary E. Coli because of the high concentrations achieved.
***'''The concentration of the antimicrobial agent achieved in blood is not important in treatment of uncomplicated UTIs. However, blood levels are critical in patients with bacteremia and febrile urinary infections consistent with parenchymal involvement of the kidney and prostate'''
**'''<span style="color:#ff0000">In patients with renal insufficiency, dosage modifications are necessary for antibiotics that are renally cleared, including:'''
**#'''<span style="color:#ff0000">Ciprofloxacin'''
**#'''<span style="color:#ff0000">Nitrofurantoin'''
**#'''<span style="color:#ff0000">Trimethoprim/sulfamethoxazole'''
**#'''<span style="color:#ff0000">Trimethoprim'''
**#'''<span style="color:#ff0000">Amoxicillin'''
**#'''<span style="color:#ff0000">Piperacillin/tazobactam'''
**#'''<span style="color:#ff0000">Cephalexin'''
**#'''<span style="color:#ff0000">Cefuroxime'''
**#'''<span style="color:#ff0000">Levofloxacin'''
**#'''<span style="color:#ff0000">Clarithromycin'''
**#'''<span style="color:#ff0000">Tetracyclin'''
***'''In renal failure, the kidneys may not be able to concentrate an antimicrobial agent in the urine; hence, difficulty in eradicating bacteria may occur.'''
**Urinary tract obstruction may reduce concentration of antimicrobial agents within the urine.
*'''Bacterial resistance'''
**'''Mechanisms (3)'''
**#'''Inherited chromosomal-mediated'''
**#'''Acquired chromosomal'''
**#'''Extrachromosomal (plasmid)-mediated'''
***'''Inherited chromosomal resistance'''
****Exists in a bacterial species because of the absence of the proper mechanism on which the antimicrobial agent can act. For example, '''Proteus and Pseudomonas species are always resistant to nitrofurantoin'''
***'''Acquired chromosomal resistance'''
****'''Caused by exposure of an organism to antimicrobial agents'''
***'''Extrachromosomal-mediated resistance'''
****'''May be acquired and transferable via plasmids, which contain the genetic material for the resistance'''
*****'''This so-called R-factor resistance occurs in the bowel flora and is much more common than selection of pre-existing mutants in the urinary tract.'''
*****'''All antibiotic classes are capable of causing plasmid-mediated resistance. However, for the fluoroquinolones, resistance is rarely transmitted by plasmids, and nitrofurantoin plasmid-mediated resistance has not been reported.'''
******'''Clinical implication: because the bowel flora is the major reservoir for bacteria that ultimately colonize the urinary tract, infections that occur after antibiotic therapy and that can cause plasmid-mediated resistance are commonly caused by organisms with multidrug resistance. However, resistant E. coli in the bowel flora that infect the urinary tract almost always show susceptibility to nitrofurantoin or to the quinolones.'''
**'''Antibiotic resistance is also influenced by the duration and amount of antibiotic agent used.'''