Tetracyclines

Microbiology: The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines, including doxycycline, have a similar antimicrobial spectrum of activity against a wide range of gram-positive and gram-negative microorganisms. Cross-resistance of these microorganisms to tetracyclines is common.

Indications:
Doxycycline is indicated for the treatment of the following infections:

• Rocky mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.
• Respiratory tract infections caused by Mycoplasma pneumoniae.
• Lymphogranuloma venereum caused by Chlamydia trachomatis.
• Psittacosis (ornithosis) caused by Chlamydia psittaci.
• Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated as judged by immunofluorescence.
• Inclusion conjunctivitis caused by Chlamydia trachomatis.
• Uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydia trachomatis.
• Nongonococcal urethritis caused by Ureaplasma urealyticum.
• Relapsing fever due to Borrelia recurrentis.

Doxycycline is also indicated for the treatment of infections caused by the following gram-negative microorganisms:

• Chancroid caused by Haemophilus ducreyi.
• Plague due to Yersinia pestis (formerly Pasteurella pestis).
• Tularemia due to Francisella tularensis (formerly Pasteurella tularensis).
• Cholera caused by Vibrio cholerae (formerly Vibrio comma).
• Campylobacter fetus infections caused by Campylobacter fetus (formerly Vibrio fetus).
• Brucellosis due to Brucella species (in conjunction with streptomycin).
• Bartonellosis due to Bartonella bacilliformis.
• Granuloma inguinale caused by Calymmatobacterium granulomatis.

Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended.

Doxycycline is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:
--Escherichia coli
--Enterobacter aerogenes (formerly Aerobacter aerogenes)
--Shigella species
--Acinetobacter species (formerly Mima species and Herellea species)
--Respiratory tract infections caused by Haemophilus influenzae.
--Respiratory tract and urinary tract infections caused by Klebsiella species.

Doxycycline is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:
--Upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae).

--Skin and skin structure infections caused by Staphylococcus aureus.

--Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

Doxycycline is not the drug of choice in the treatment of any type of staphylococcal infections.

When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections:
--Uncomplicated gonorrhea caused by Neisseria gonorrhoeae.
--Syphilis caused by Treponema pallidum.
--Yaws caused by Treponema pertenue.
--Listeriosis due to Listeria monocytogenes.
--Vincent's infection caused by Fusobacterium fusiforme.
--Actinomycosis caused by Actinomyces israelii.
--Infections caused by Clostridium species.

In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides.

In severe acne, doxycycline may be useful adjunctive therapy

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Dosing:
Children ≥ 8 years (<45 kg): Susceptible infections: Oral, I.V.: 2-5 mg/kg/day in 1-2 divided doses, not to exceed 200 mg/day
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Children >8 years (>45 kg) and Adults: Susceptible infections: Oral, I.V.: 100-200 mg/day in 1-2 divided doses
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Acute gonococcal infection (PID) in combination with another antibiotic: 100 mg every 12 hours until improved, followed by 100 mg orally twice daily to complete 14 days
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Community-acquired pneumonia: 100 mg twice daily
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Lyme disease: Oral: 100 mg twice daily for 14-21 days
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Early syphilis: 200 mg/day in divided doses for 14 days
Late syphilis: 200 mg/day in divided doses for 28 days

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Uncomplicated chlamydial infections: 100 mg twice daily for ≥ 7 days
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Endometritis, salpingitis, parametritis, or peritonitis: 100 mg I.V. twice daily with cefoxitin 2 g every 6 hours for 4 days and for ≥ 48 hours after patient improves; then continue with oral therapy 100 mg twice daily to complete a 10- to 14-day course of therapy
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Sclerosing agent for pleural effusion injection (unlabeled use): 500 mg as a single dose in 30-50 mL of NS or SWI
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Periodontitis: Oral (Periostat®): 20 mg twice daily as an adjunct following scaling and root planing; may be administered for up to 9 months. Safety beyond 12 months of treatment and efficacy beyond 9 months of treatment have not been established.

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Adults:
Anthrax:

Inhalational (postexposure prophylaxis): Oral, I.V. (use oral route when possible): 100 mg every 12 hours for 60 days ( MMWR , 2001, 50:889-93); Note: Preliminary recommendation, FDA review and update is anticipated.

Cutaneous (treatment): Oral: 100 mg every 12 hours for 60 days. Note: In the presence of systemic involvement, extensive edema, lesions on head/neck, refer to I.V. dosing for treatment of inhalational/gastrointestinal/oropharyngeal anthrax

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Supplied:
Capsule, as hyclate: 50 mg, 100 mg
Capsule, as monohydrate (Monodox®): 50 mg, 100 mg
Capsule, coated pellets, as hyclate (Doryx®): 75 mg, 100 mg

Injection, powder for reconstitution, as hyclate (Doxy-100®): 100 mg
Powder for oral suspension, as monohydrate (Vibramycin®): 25 mg/5 mL (60 mL)
Syrup, as calcium (Vibramycin®): 50 mg/5 mL (480 mL)
Tablet, as hyclate: 100 mg
Periostat®: 20 mg
Vibra-Tabs®: 100 mg
Tablet, as monohydrate (Adoxa™): 50 mg, 75 mg, 100 mg

--Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox and tick fevers caused by rickettsiae
--Respiratory tract infections caused by Mycoplasma pneumoniae.
--Lymphogranuloma venereum caused by Chlamydia trachomatis.
--Psittacosis (Ornithosis) due to Chlamydia psittaci.
--Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immunofluorescence.
--Inclusion conjunctivitis caused by Chlamydia trachomatis.
--Nongonococcal urethritis, endocervical, or rectal infections in adults caused by Ureaplasma urealyticum or Chlamydia trachomatis.
--Relapsing fever due to Borrelia recurrentis.
--Chancroid caused by Haemophilus ducreyi.
--Plague due to Yersinia pestis.
--Tularemia due to Francisella tularensis.
--Cholera caused by Vibrio cholerae.
--Campylobacter fetus infections caused by Campylobacter fetus.
--Brucellosis due to Brucella species (in conjunction with streptomycin).
--Bartonellosis due to Bartonella bacilliformis.
--Granuloma inguinale caused by Calymmatobacterium granulomatis.

Minocycline is indicated for the treatment of infections caused by the following gram-negative microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:

--Escherichia coli.
--Enterobacter aerogenes.
--Shigella species.
--Acinetobacter species.

Respiratory tract infections caused by Haemophilus influenzae.
Respiratory tract and urinary tract infections caused by Klebsiella species.
MINOCIN® Pellet-Filled Capsules are indicated for the treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:

Upper respiratory tract infections caused by Streptococcus pneumoniae.
Skin and skin structure infections caused by Staphylococcus aureus. (Note: Minocycline is not the drug of choice in the treatment of any type of staphylococcal infection.)
When penicillin is contraindicated, minocycline is an alternative drug in the treatment of the following infections:

Uncomplicated urethritis in men due to Neisseria gonorrhoeae and for the treatment of other gonococcal infections.
--Infections in women caused by Neisseria gonorrhoeae.
--Syphilis caused by Treponema pallidum subspecies pallidum.
--Yaws caused by Treponema pallidum subspecies pertenue.
--Listeriosis due to Listeria monocytogenes.
--Anthrax due to Bacillus anthracis.
--Vincent's infection caused by Fusobacterium fusiforme.
--Actinomycosis caused by Actinomyces israelii.

Infections caused by Clostridium species.
In acute intestinal amebiasis, minocycline may be a useful adjunct to amebicides.

In severe acne, minocycline may be useful adjunctive therapy.

Oral minocycline is indicated in the treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx. In order to preserve the usefulness of minocycline in the treatment of asymptomatic meningococcal carriers, diagnostic laboratory procedures, including serotyping and susceptibility testing, should be performed to establish the carrier state and the correct treatment. It is recommended that the prophylactic use of minocycline be reserved for situations in which the risk of meningococcal meningitis is high.

Oral minocycline is not indicated for the treatment of meningococcal infection.

Although no controlled clinical efficacy studies have been conducted, limited clinical data show that oral minocycline hydrochloride has been used successfully in the treatment of infections caused by Mycobacterium marinum.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MINOCIN® (minocycline hydrochloride) Pellet-Filled Capsules and other antibacterial drugs, MINOCIN ® (minocycline hydrochloride) Pellet-Filled Capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy

Dosing:

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Children >8 years:
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Oral, I.V.: Initial: 4 mg/kg followed by 2 mg/kg/dose every 12 hours

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Adults:
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Infection: Oral, I.V.: 200 mg stat, 100 mg every 12 hours not to exceed 400 mg/24 hours
Acne: Oral: 50 mg 1-3 times/day

May be taken with food or milk. Administer with adequate fluid to decrease the risk of esophageal irritation and ulceration.

Dosage adjustment in renal impairment: Consider decreasing dose or increasing dosing interval with renal impairment.

Supplied:
Capsule, as hydrochloride: 50 mg, 75 mg, 100 mg
Dynacin®: 50 mg, 75 mg, 100 mg
Capsule, pellet-filled, as hydrochloride (Minocin®): 50 mg, 100 mg
Injection, powder for reconstitution, as hydrochloride (Minocin®): 100 mg
Tablet, as hydrochloride (Dynacin®): 50 mg, 75 mg, 100 mg

Dosing:
Oral:
Children >8 years: 25-50 mg/kg/day in divided doses every 6 hours
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Adults: 250-500 mg/dose every 6 hours

Helicobacter pylori eradication: 500 mg 2-4 times/day depending on regimen; requires combination therapy with at least one other antibiotic and an acid-suppressing agent (proton pump inhibitor or H2 blocker)
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Dosing interval in renal impairment:
Clcr 50-80 mL/minute: Administer every 8-12 hours
Clcr 10-50 mL/minute: Administer every 12-24 hours
Clcr<10 mL/minute: Administer every 24 hours

Dialysis: Slightly dialyzable (5% to 20%) via hemo- and peritoneal dialysis or via continuous arteriovenous or venovenous hemofiltration; no supplemental dosage necessary

Dosing adjustment in hepatic impairment: Avoid use or maximum dose is 1 g/day
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Administration
Should be administered on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption. Administer at least 1-2 hours prior to, or 4 hours after antacid because aluminum and magnesium cations may chelate with tetracycline and reduce its total absorption.

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Supplied:
Capsule, as hydrochloride: 250 mg, 500 mg

Suspension, oral, as hydrochloride (Sumycin®): 125 mg/5 mL (480 mL) [contains sodium benzoate and sodium metabisulfite; fruit flavor]

Tablet, as hydrochloride (Sumycin®): 250 mg, 500 mg