DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1544 dermal ulcers, the local application of the antibiotic may be of some
help in eradicating sensitive bacteria. Unlike several other antibiotics
used topically, bacitracin rarely produces hypersensitivity.
Suppurative conjunctivitis and infected corneal ulcer respond well to
the topical use of bacitracin when caused by susceptible bacteria.
Bacitracin has been used with limited success for eradication of nasal
carriage of staphylococci. Oral bacitracin has been used with some
success for the treatment of antibiotic-associated diarrhea caused by
C. difficile. Bacitracin is used by neurosurgeons to irrigate the
meninges intraoperatively as an alternative to vancomycin. It has no
direct toxicity on neurons.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Untoward Effects. Serious nephrotoxicity results from the parenteral
use of this antibiotic. Hypersensitivity reactions rarely result from
topical application.
MUPIROCIN
Mupirocin (BACTROBAN) is derived from a fermentation
product of Pseudomonas fluorescens. It is for topical
use only.
(CH 2 ) 8
Antimicrobial Activity. Mupirocin is active against many grampositive
and selected gram-negative bacteria. It has good activity
with MICs ≤1 μg/mL against Streptococcus pyogenes and methicillin-susceptible
and methicillin-resistant strains of S. aureus. It is
bactericidal at concentrations achieved with topical application.
Mechanism of Action and Mupirocin Resistance. Mupirocin
inhibits bacterial protein synthesis by reversible binding and inhibition
of isoleucyl transfer-RNA synthetase. There is no crossresistance
with other classes of antibiotics. Low-level resistance,
which is not clinically significant, is due to mutations of the host
gene encoding isoleucyl transfer-RNA synthetase or an extra chromosomal
copy of a gene encoding a modified isoleucyl transfer-
RNA synthetase (Ramsey et al., 1996; Udo et al., 2001). High-level
resistance (MIC >1 mg/mL) is mediated by a plasmid or chromosomal
copy of mupA, which encodes a “bypass” synthetase that
binds mupirocin poorly (Udo et al., 2001).
Absorption, Fate, and Excretion. Systemic absorption through
intact skin or skin lesions is minimal. Any mupirocin that is absorbed
is rapidly metabolized to inactive monic acid.
Therapeutic Uses and Dosage. Mupirocin is available as a 2%
cream and a 2% ointment for dermatologic use and as a 2% ointment
for intranasal use. The dermatologic preparations are indicated
for treatment of traumatic skin lesions and impetigo secondarily
infected with S. aureus or S. pyogenes.
The nasal ointment is approved for eradication of S. aureus
nasal carriage. Mupirocin is highly effective in eradicating S. aureus
carriage (Laupland and Conly, 2003). Because S. aureus colonization
often precedes infection, eradication of carriage by intranasal application
of mupirocin might reduce the risk of later infection.
However, two clinical trials failed to demonstrate that mupirocin prophylaxis
reduces nosocomial S. aureus infections (Kalmeijer et al.,
2002; Wertheim et al., 2004). A third large study found that S. aureus
nasal carriers had fewer S. aureus nosocomial infections of any site,
but it failed to show a reduction in S. aureus surgical site infections,
the primary end point of the study (Perl et al., 2002). The accumulated
evidence indicates that patients who stand to benefit from
mupirocin prophylaxis are those with proven S. aureus nasal colonization
plus risk factors for distant infection or a history of skin or
soft-tissue infections. General inpatient populations and individuals
lacking specific risk factors for S. aureus infection are not likely to
benefit from mupirocin prophylaxis.
Untoward Effects. Mupirocin may cause irritation and sensitization
at the site of application. Contact with the eyes should be avoided
because mupirocin causes tearing, burning, and irritation that may
take several days to resolve. Systemic reactions to mupirocin occur
rarely, if at all. Polyethylene glycol present in the ointment can be
absorbed from damaged skin. Application of the ointment to large
surface areas should be avoided in patients with moderate to severe
renal failure to avoid accumulation of polyethylene glycol.
CLINICAL SUMMARY
Doxycycline, the most important member of the tetracyclines,
is a drug of choice for sexually transmitted
diseases, rickettsial infections, plague, brucellosis,
tularemia, and spirochetal infections. It is also an important
agent for treatment of respiratory tract infections,
given its activity against S. pneumoniae, Haemophilus
spp., and atypical pneumonia pathogens; and for skin and
soft-tissue infections caused by community strains of
methicillin-resistant S. aureus, for which minocycline
also is particularly active. Glycylcyclines, beginning with
tigecycline, have restored much of the activity of the
tetracyclines against bacteria that have become refractory
to first- and second-generation tetracyclines, including
aerobic and anaerobic gram-negative organisms as
well as refractory gram-positive organisms.
Macrolides and ketolides are effective for treatment
of respiratory tract infections caused by the common
pathogens of community-acquired pneumonia,
including S. pneumoniae, Haemophilus spp., Chlamydia,
mycoplasma, and Legionella. They generally are welltolerated,
orally bioavailable, and except for erythromycin,
effective in once or twice-daily dosing. All except
azithromycin have important drug interactions because
they inhibit hepatic CYPs.
Chloramphenicol is rarely indicated in the U.S.
and Europe because it can cause irreversible bone marrow
toxicity and because less toxic drugs are readily
available. However, it continues to be an important