• Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree. They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.

    Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/mL of doxycycline at 2 hours decreasing to 1.45 mcg/mL at 24 hours. Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1-5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Studies have shown no significant difference in serum half-life of doxycycline (range 18-22 hours) in individuals with normal and severely impaired renal function.

    Hemodialysis does not alter serum half-life.

    Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues.

  • 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 organisms. Cross-resistance of these organisms to tetracyclines is common.

  • Gram-Negative Bacteria

  • Neisseria gonorrhoeaeCalymmatobacterium granulomatisHaemophilus ducreyiHaemophilus influenzaeYersinia pestis (formerly Pasteurella pestis) Francisella tularensis (formerly Pasteurelia tularensis) Vibrio cholera (formerly Vibrio comma) Bartonella bacilliformisBrucella species

    Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended:

    Escherichia coliKlebsiella speciesEnterobacter aerogenesShigella speciesAcinetobacter species (formerly Mima species and Herellea species) Bacteroides species

  • Gram-Positive Bacteria

  • Because many strains of the following groups of gram-positive microorganisms have been shown to be resistant to tetracycline, culture and susceptibility testing are recommended. Up to 44 percent of strains of Streptococcus pyogenes and 74 percent of Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore, tetracycline should not be used for streptococcal disease unless the organism has been demonstrated to be susceptible.

    Streptococcus pyogenesStreptococcus pneumoniaeEnterococcus group (Streptococcus faecalis and Streptococcus faecium) Alpha-hemolytic streptococci (viridans group)

  • Other Microorganisms

  • Rickettsiae Clostridium species
    Chlamydia psittaci Fusobacterium fusiforme
    Chlamydia trachomatis Actinomyces species
    Mycoplasma pneumoniae Bacillus anthracis
    Ureaplasma urealyticum Propionbacterium acnes
    Borrelia recurrentis Entamoeba species
    Treponema pallidum Balantidium coli
    Treponema pertenue Plasmodium falciparum

    Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum but not against the gametocytes of P. falciparum. The precise mechanism of action of the drug is not known.

  • Susceptibility tests

  • Diffusion techniques: Quantitative methods that require measurement of zone diameters give the most precise estimate of the susceptibility of bacteria to antimicrobial agents. One such standard procedure1 has been recommended for use with disks to test susceptibility of organisms to doxycycline, uses the 30-mcg tetracycline-class disk or the 30- mcg doxycycline disk. Interpretation involves the correlation of the diameter obtained in the disk test with the minimum inhibitory concentration (MIC) for tetracycline or doxycycline, respectively.

    Reports from the laboratory giving results of the standard single-disk susceptibility test with a 30-mcg tetracycline-class disk or the 30-mcg doxycycline disk should be interpreted according to the following criteria:

    Zone Diameter (mm) Interpretation
    tetracycline doxycycline
    =19 =16 Susceptible
    15-18 13-15 Intermediate
    =14 =12 Resistant

    A report of “susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of “intermediate” suggests that the organism would be susceptible if a high dosage is used or if the infection is confined to tissues and fluids in which antimicrobial levels are attained. A report of “resistant” indicates that achievable concentrations are unlikely to be inhibitory, and other therapy should be selected.

    Standardized procedures require the use of laboratory control organisms. The 30-mcg tetracycline-class disk or the 30-mcg doxycycline disk should give the following zone diameters:

    Organism Zone Diameter (mm)
    tetracycline doxycycline
    E. coli ATCC 25922 18-25 18-24
    S. aureus ATCC 25923 19-28 23-29
  • Dilution techniques

  • Use a standardized dilution method2 (broth, agar, microdilution) or equivalent with tetracycline powder. The MIC values obtained should be interpreted according to the following criteria:

    MIC (mcg/mL) Interpretation
    =4 Susceptible
    8 Intermediate
    =16 Resistant

    As with standard diffusion techniques, dilution methods require the use of laboratory control organisms. Standard tetracycline powder should provide the following MIC values:

    Organism MIC (mcg/mL)
    E. coli ATCC 25922 1.0-4.0
    S. aureus ATCC 29213 0.25-1.0
    E. faecalis ATCC 29212 8-32
    P. aeruginosa ATCC 27853 8-32
  • Drug Information Provided by National Library of Medicine (NLM).