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

Intra-abdominal Infections. Increasing resistance among
Enterobacteriaceae and gram-negative anaerobes limit the utility of
the tetracyclines for intra-abdominal infections. However, tigecycline
possesses excellent activity against these pathogens as well as
Enterococcus and has demonstrated effectiveness in clinical trials
for complicated intra-abdominal infections (Oliva et al., 2005).
GI Infections. Therapy with the tetracyclines is often ineffective in
infections caused by Shigella, Salmonella, or other Enterobacteriaceae
because of a high prevalence of drug-resistant strains in many areas.
Resistance limits the usefulness of tetracyclines for travelers’ diarrhea.
Doxycycline (300 mg as a single dose) is effective in reducing
stool volume and eradicating Vibrio cholerae from the stool within
48 hours. Antimicrobial agents, however, are not substitutes for fluid
and electrolyte replacement in this disease. In addition, some strains
of V. cholerae are resistant to tetracyclines.
Urinary Tract Infections. Tetracyclines are no longer recommended
for routine treatment of urinary tract infections because many enteric
organisms that cause these infections, including E. coli, are resistant.
There is little experience in using tigecycline for urinary tract infections;
based on its in vitro activity, it should be adequate.
Sexually Transmitted Diseases. Because of resistance, doxycycline
no longer is recommended for gonococcal infections. If coinfection
with C. trachomatis has not been excluded, then either doxycycline
or azithromycin should be administered in addition to an agent effective
for gonococcal urethritis (Workowski and Berman, 2006).
C. trachomatis often is a coexistent pathogen in acute pelvic
inflammatory disease, including endometritis, salpingitis, parametritis,
and/or peritonitis. Doxycycline, 100 mg intravenously twice daily,
is recommended for at least 48 hours after substantial clinical improvement,
followed by oral therapy at the same dosage to complete a
14-day course. Doxycycline usually is combined with cefoxitin or
cefotetan (Chapter 53) to cover anaerobes and facultative aerobes.
Acute epididymitis is caused by infection with C. trachomatis
or N. gonorrhoeae in men <35 years of age. Effective regimens
include a single injection of ceftriaxone (250 mg) plus doxycycline,
100 mg orally twice daily for 10 days. Sexual partners of patients
with any of these conditions also should be treated.
Nonspecific urethritis is often due to Chlamydia trachomatis.
Doxycycline, 100 mg every 12 hours for 7 days, is effective; however,
azithromycin is usually preferred because it can be given as a
single 1-g dose. Doxycycline (100 mg twice daily for 21 days) is
first-line therapy for treatment of lymphogranuloma venereum. The
size of buboes decreases within 4 days, and inclusion and elementary
bodies entirely disappear from the lymph nodes within 1 week.
Rectal pain, discharge, and bleeding of lymphogranulomatous proctitis
are decreased markedly. When relapses occur, treatment is
resumed with full doses and is continued for longer periods.
Nonpregnant penicillin-allergic patients who have primary,
secondary, or latent syphilis can be treated with a tetracycline regimen
such as doxycycline, 100 mg orally twice daily for 2 weeks.
Tetracyclines should not be used for treatment of neurosyphilis.
Rickettsial Infections. Tetracyclines are effective and may be lifesaving
in rickettsial infections, including Rocky Mountain spotted
fever, recrudescent epidemic typhus (Brill’s disease), murine typhus,
scrub typhus, rickettsialpox, and Q fever. Clinical improvement often
is evident within 24 hours after initiation of therapy. Doxycycline is
the drug of choice for treatment of suspected or proven Rocky
Mountain spotted fever in adults and in children, including those
<9 years of age, in whom the risk of staining of permanent teeth
is outweighed by the seriousness of this potentially fatal infection
(Masters et al., 2003).
Anthrax. Doxycycline, 100 mg every 12 hours (2.2 mg/kg every
12 hours for children weighing <45 kg), is indicated for prevention
or treatment of anthrax. It should be used in combination with
another agent when treating inhalational or GI infection. The recommended
duration of therapy is 60 days for exposures occurring as
an act of bioterrorism.
Local Application. Except for local use in the eye, topical use of the
tetracyclines is not recommended. Their use in ophthalmic therapy
is discussed in previous versions of this text. Minocycline sustainedrelease
microspheres for subgingival administration are used in dentistry
as an adjunct to scaling and root planing procedures to reduce
pocket depth in patients with adult periodontitis.
Other Infections. Tetracyclines in combination with rifampin or
streptomycin are effective for acute and chronic infections caused
by Brucella melitensis, Brucella suis, and Brucella abortus. Effective
regimens are doxycycline, 200 mg per day, plus rifampin, 600-900 mg
daily for 6 weeks, or the usual dose of doxycycline plus streptomycin
1 g daily, intramuscularly. Relapses usually respond to a second
course of therapy. Although streptomycin is preferable, tetracyclines
also are effective in tularemia (Ellis et al., 2002). Both the
ulceroglandular and typhoidal types of the disease respond well.
Actinomycosis, although most responsive to penicillin G, may be
successfully treated with a tetracycline. Minocycline is an alternative
for the treatment of nocardiosis, but a sulfonamide should be used
concurrently. Yaws and relapsing fever respond favorably to the tetracyclines.
Tetracyclines are useful in the acute treatment and for prophylaxis
of leptospirosis (Leptospira spp.). Borrelia spp., including
B. recurrentis (relapsing fever) and B. burgdorferi (Lyme disease),
respond to therapy with a tetracycline. The tetracyclines have been
used to treat susceptible atypical mycobacterial pathogens, including
M. marinum.
Untoward Effects
Gastrointestinal. All tetracyclines can produce GI irritation, most
commonly after oral administration. GI distress is also characteristic
of tigecycline administration. Epigastric burning and distress,
abdominal discomfort, nausea, vomiting, and diarrhea may occur.
Tolerability can be improved by administering these drugs with food,
but tetracyclines should not be taken with dairy products or antacids.
Tetracycline has been associated with esophagitis, esophageal ulcers,
and pancreatitis.
Many of the tetracyclines are incompletely absorbed from the
GI tract, and high concentrations in the bowel can markedly alter
enteric flora. Sensitive aerobic and anaerobic coliform microorganisms
and gram-positive spore-forming bacteria are suppressed
markedly during long-term tetracycline regimens. As the fecal coliform
count declines, overgrowth of tetracycline-resistant microorganisms
occurs, particularly of yeasts (Candida spp.), enterococci,
Proteus, and Pseudomonas. Moniliasis, thrush, or Candida-associated
esophagitis may arise during therapy with tetracyclines. Tetracyclines
and glycylcyclines may occasionally produce pseudomembranous
colitis caused by Clostridium difficile; pseudomembranous colitis
caused by overgrowth of C. difficile is a potentially life-threatening
complication.
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CHAPTER 55
PROTEIN SYNTHESIS INHIBITORS AND MISCELLANEOUS ANTIBACTERIAL AGENTS