Infectious Diseases II
studies, patients with secondary bacteremia treated with tigecycline were compared
with patients treated with other antibiotics. Overall, no significant differences in
outcomes were seen. Despite these results, clinicians should exert caution with the
use of tigecycline for bacteremia and should reserve tigecycline for pathogens when
no other antibiotics are viable options.
| (3) | Primarily biliary elimination |
|---|---|
| (4) | Urinary elimination is 8%β11%. The low urinary elimination limits tigecyclineβs role |
in treating UTIs. The use of tigecycline for treating multidrug-resistant UTIs has
been reported only in case reports, with most reports showing treatment success.
However, a recent evaluation of tigecycline for the treatment of KPC bacteriuria
indicated a correlation with the subsequent development of tigecycline resistance.
Without further data, tigecycline should not routinely be used for UTIs when other
treatment options are available.
| (5) | Poor penetration into lung epithelial lining fluid, which is in contrast to high penetration |
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into lung alveolar cells. This characteristic may partly explain the findings of a study
evaluating tigecycline compared with imipenem for the treatment of hospital-acquired
pneumonia. This study showed that tigecycline had a lower treatment success rate
than imipenem. The difference in treatment success was mainly attributable to the
significant differences in patients with ventilator-associated pneumonia. There was
also a trend toward increased mortality in the subgroup of patients with ventilator-
associated pneumonia.
| (e) | The FDA issued a safety warning in 2010 indicating a possible increased mortality risk |
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associated with the use of tigecycline compared with other drugs used to treat a variety
of other serious infections. This was compiled using several phase III studies in which
tigecycline had been proven noninferior to other standard treatments. Subsequently,
several other meta-analyses were published with conflicting results regarding tigecyclineβs
increased mortality risk.
| (f) | Given tigecyclineβs possible shortcomings, it seems prudent to avoid the routine use of |
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tigecycline in infections when other treatment options are available. However, tigecycline
may be one of the few remaining antibiotic options for treating carbapenem-resistant
pathogens. When tigecycline must be used because of limited treatment options, clinicians
should consider administering combination therapy with other agents that have in vitro
susceptibility.
| (g) | Resistance to tigecycline has been reported. Clinicians should seek confirmation from |
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their microbiology laboratory regarding tigecycline sensitivity. Of note, CLSI currently
has no recommendation for MIC breakpoint for tigecycline against Acinetobacter spp.
The MIC breakpoint for sensitivity against Enterobacterales is 2 mcg/mL or less.
ii.
Polymyxins:
| (a) | Colistin (polymyxin E) |
|---|---|
| (1) | Mechanism of action: A cationic cyclic decapeptide that functions by displacing |
calcium and magnesium from the outer cell membrane, hence changing the
permeability of the cell membrane to allow insertion of the molecule into the cell
membrane. Once the molecule is inserted into the cell membrane, it disrupts the cell
membrane integrity and subsequently leads to cell death.
| (2) | Spectrum of activity: Covers only gram-negative bacteria, including CRE. Does not |
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cover Proteus, Providencia, Burkholderia, Serratia, or Stenotrophomonas
| (3) | First used in the United States in the 1960s but fell out of favor because of reports of |
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nephrotoxicity and neurotoxicity