Table 1. The tetracyclines
|
Agent |
Brand Name |
Dosage Forms & Strength |
|
|
Short acting |
|
|
|
|
|
Tetracycline |
Sumycin® |
Suspension - 125 mg/5 ml |
|
|
|
|
|
|
|
Tetracycline HCl |
various generic, Achromycin V®, Ala-Tet®, Nor-Tet®, Panmycin®, Robitet Robicaps®, Sumycin®, Teline®, Tetracap®, Tetralan®, Tetram®, Tetracycline® |
Capsules - 100, 250, 500 mg Tablets - 250, 500 mg |
|
|
|
various generic |
Suspensions - 125 mg/5 ml |
|
|
|
Achromycin IM® |
Powder for IM injection- 100, 250 mg |
|
|
|
Achromycin IV® |
Powder for IV injection - 250, 500 mg |
|
|
Oxytetracycline HCl |
various generic, E.P. Mycin®, Terramycin®, Uri-Tet® |
Capsules - 250 mg |
|
|
|
Terramycin IM® |
Injection - 50, 125 mg with 2% lidocaine |
|
Intermediate acting |
|
|
|
|
|
Demeclocycline |
Declomycin® |
Capsules - 150 mg Tablets - 150, 300 mg |
|
|
|
|
|
|
Long acting |
|
|
|
|
|
Doxycycline hyclate |
various generic, Doxychel Hyclate®, Doxy Caps®, Doryx®, Doxy 100, 200®, Vibra-Tabs®, Vibramycin® |
Capsules - 50, 100 mg Tablets - 50, 100 mg Powder for injection - 100, 200 mg |
|
|
|
|
|
|
|
Doxycycline calcium |
Vibramycin® |
Syrup - 50 mg/5 ml |
|
|
|
|
|
|
|
Doxycycline monohydrate |
Vibramycin® |
Powder for oral suspension - 25 mg/5 ml |
|
|
|
|
|
|
|
Minocycline |
Minocin IV® |
Powder for injection - 100 mg |
|
|
|
|
|
|
|
Minocycline HCl |
Minocin® |
Capsule - 50, 100 mg Tablet - 50, 100 mg Oral suspension - 50 mg/5 ml |
Table 2. In Vitro Susceptibilities
|
|
|
Tetracycline |
Doxycycline |
||||
|
Organism |
MIC50 |
MIC90 |
Range |
MIC50 |
MIC90 |
Range |
|
|
Gram-positive aerobes |
|
|
|
|
|
|
|
|
|
Staphylococcus aureus |
3.1 |
> 25 |
0.8 - > 25 |
1.6 |
> 25 |
0.4 - > 25 |
|
|
Streptococcus pneumonia |
0.8 |
8 |
0.125 - >128 |
0.4 |
0.4 |
0.4 |
|
|
Streptococcus pyogenes |
0.8 |
6.3 |
0.4 - > 25 |
0.4 |
0.8 |
0.4 - 25 |
|
|
Streptococcus agalacticae |
1.6 |
> 25 |
1.6 - > 25 |
0.8 |
25 |
0.8 - 25 |
|
|
Enterococcus spp. |
> 25 |
> 25 |
6.3 - > 25 |
> 25 |
> 25 |
6.3 - > 25 |
|
Gram-negative aerobes |
|
|
|
|
|
|
|
|
|
Campylobacter jejuni |
0.8 |
> 25 |
0.4 - > 25 |
0.4 |
12.5 |
12.5 |
|
|
Enterobacter spp. |
3.1 |
25 |
0.8 - > 25 |
25 |
> 25 |
6.3 - > 25 |
|
|
Escherichia coli |
12.5 |
> 25 |
3.1 - > 25 |
12.5 |
> 25 |
3.1 - > 25 |
|
|
Haemophilus influenzae |
6.3 |
12.5 |
3.1 - 12.5 |
1.6 |
3.1 |
1.6 - 6.3 |
|
|
Klebsiella pneumoniae |
> 25 |
> 25 |
6.3 - > 25 |
> 25 |
> 25 |
6.3 - > 25 |
|
|
Neisseria gonorrhoeae |
0.8 |
6.3 |
0.4 - 6.3 |
0.4 |
6.3 |
0.4 - 6.3 |
|
|
Neisseria meningitidis |
0.8 |
3.1 |
0.8 - 3.1 |
1.6 |
6.3 |
1.6 - 6.3 |
|
|
Proteus mirabilis |
> 25 |
> 25 |
> 25 |
> 25 |
> 25 |
> 25 |
|
|
Proteus spp. (indole +) |
> 25 |
> 25 |
> 25 |
> 25 |
> 25 |
> 25 |
|
|
Pseudomonas aeruginosa |
> 25 |
> 25 |
> 25 |
> 25 |
> 25 |
> 25 |
|
|
Pseudomonas pseudomallei |
1.6 |
3.1 |
1.6 - 3.1 |
|
|
|
|
|
Shigella spp. |
3.1 |
> 25 |
0.8 - > 25 |
|
|
|
|
Gram-positive anaerobes |
|
|
|
|
|
|
|
|
|
Clostridium perfringens |
2.0 |
> 32 |
0.5 - > 32 |
0.5 |
16 |
0.5 - 16 |
|
|
Peptococcus |
16 |
32 |
0.5 - > 32 |
4.0 |
8.0 |
0.5 - 32 |
|
|
Peptostreptococcus |
4.0 |
32 |
0.5 - > 32 |
2.0 |
8.0 |
0.5 - 16 |
|
Gram-negative anaerobes |
|
|
|
|
|
|
|
|
|
Bacteroides fragilis |
16 |
> 32 |
0.5 - > 32 |
2.0 |
16 |
0.5 - 32 |
|
|
Bacteroides melaninogenicus |
0.5 |
8.0 |
0.5 - > 32 |
0.5 |
2.0 |
0.5 - > 32 |
MIC50 and MIC90, MICs at which 50% and 90% of strains are inhibited. Most bacterial organisms: Susceptible MIC < 4 mg/mL,
Intermediate MIC 8 mg/mL, Resistant MIC > 16 mg/mL.
Haemophilus influenzae & Streptococcus pneumoniae: Susceptible MIC < 2 mg/mL, Intermediate MIC 4 mg/mL, Resistant
MIC > 8 mg/mL. Neisseria gonorrhoeae: Susceptible MIC < 0.25 mg/mL, Intermediate MIC 0.5 - 1.0 mg/mL, Resistant MIC > 2 mg/mL.
Table 3. Pharmacokinetic Parameters
|
Drug |
% GI absorption (fasting) |
Cmax (serum) mg/ml |
tmax (hours) |
t1/2 (hours) |
t1/2 (renal failure) (hours) |
% serum protein binding |
Apparent volume of distribution (L/kg) |
Renal clearance (ml/min/ 1.73m2) |
% urinary recovery |
% fecal recovery |
|
Tetracycline |
75 – 80 |
1.5 – 5a |
2 - 4 |
6 - 12 |
57 - 120 |
20 - 65 |
108 |
74 |
48 - 60 |
|
|
Demeclocycline |
60 – 80 |
0.9 - 1.7b |
3 - 4 |
10 - 17 |
42 - 68 |
36 - 91 |
121 |
35 |
44 |
31 |
|
Doxycycline |
90 – 100 |
1.5 - 3.6c 4 – 10d |
1.5 - 4 |
14 - 24 |
18 - 30 |
60 - 95 |
50 |
20 |
20 - 42 |
20 - 40 |
|
Minocycline |
90 – 100 |
2 - 3.5e |
1 - 4 |
11 - 26 |
12 - 30 |
55 - 76 |
60 |
9 |
4 - 19 |
20 - 34 |
a = 500 mg oral dose
b = 300 mg oral dose
c = 200 mg oral dose
d = 200 mg intravenous dose
e = 200 mg oral dose
Table Table 4. Standard Doses
|
Drug |
Adult (range) |
Pediatric (range)* children greater than 8 years of age |
|
Tetracycline |
1- 2 grams daily in 2 - 4 divided doses
500 mg for sclerosing |
25 - 50 mg/kg/day in 2 - 4 divided doses OR 0.6 - 1.2 g/m2 in 2 - 4 divided doses |
|
Demeclocycline |
150 mg every 6 hours 300 mg every 12 hours
SIADH - 600 - 1200 mg/day in 3 - 4 divided doses |
6.6 - 13.2 mg/kg/day in 2 - 4 divided doses OR 300 mg/m2 in 2 - 4 divided doses
|
|
Doxycycline |
100 - 200 mg/day given in 1 - 2 divided doses
500 mg for sclerosing |
2.2 - 4.4 mg/kg/day in 1 - 2 divided doses |
|
Minocycline |
100 - 200 mg/day in two divided doses OR 50 mg every 6 hours |
2 - 4 mg/kg divided every 12 hours |
* Tetracyclines are contraindicated in children less than 8 years of age.
Table 5. Dosage Adjustment in Renal Insufficiency
|
Drug |
Normal Dose (CrCl > 50 ml/min) |
CrCl 10 - 50 ml/min |
CrCl < 10 ml/min |
|
Tetracycline |
250 - 500 mg QID |
250 - 500 mg BID - QD |
NR* |
|
Doxycycline |
100 mg QD - BID |
same |
same |
|
Minocycline |
100 mg BID |
same |
same |
CrCl = creatinine clearance
NR = Not recommended.
Table 6. Drug /Drug and Drug/Food Interactions
|
Drug |
Effect |
Recommendation |
|
Antacids, Didanosine, Sucralfate, Multivitamins |
Decreased absorption of tetracycline |
Space administration by 2 hours |
|
Warfarin |
Increased warfarin effect |
Monitor PT, INR |
|
Kaolin, Bismuth subsalicylate |
Decreased absorption of tetracycline |
Space administration by 2 hours |
|
Barbiturates, Phenytoin, Carbamazepine |
Decreased serum concentrations of doxycycline |
Use alternative tetracycline |
|
Methoxyflurane anesthesia |
Fatal nephrotoxicity |
Avoid concomitant therapy |
|
Oral Contraceptives |
Decreased serum concentrations of oral contraceptive |
Use barrier method of birth control during tetracycline therapy |
|
Food |
Decreased absorption of tetracycline and minocycline |
Space administration or use doxycycline |
|
Dairy Products (milk) |
Decreased absorption of tetracycline and minocycline |
Space administration or use doxycycline |
|
Ethanol |
Decreased serum concentrations of doxycycline |
Use alternative tetracycline |
7. Table 7. Clinical Indications
|
Therapy of Choice |
Alternative Therapy |
||
|
Rickettsial Infections |
Mycoplasma pneumoniae |
||
|
|
Epidemic (louse-borne) Typhus |
Spirochetal Infections |
|
|
|
Brill-Zinsser Disease |
|
Treponemal pallidum (syphilis) |
|
|
Scrub Typhus |
|
Leptospirosis |
|
|
Rocky Mountain Spotted Fever |
|
Treponema pertenue (Yaws) |
|
|
Endemic (murine) Typhus |
|
Pinta |
|
|
Q Fever |
|
Bejel |
|
|
Rickettsial Pox |
Helicobacter pylori (tetracycline) |
|
|
Chlamydial Infections |
Traveler’s Diarrhea |
||
|
|
Chlamydial trachomatis (uncomplicated) |
|
Enterotoxigenic E. coli |
|
|
Lymphogranuloma venereum |
|
Shigella |
|
|
Trachoma and inclusion conjunctivitis |
|
Salmonella |
|
|
Chlamydial psittacosis pneumonia |
|
Campylobacter spp. |
|
Spirochetal Infections |
Plasmodium falciparum (malaria) |
||
|
|
Lyme - Borrelia burgdorferi |
Mycobacteria marinum (minocycline) |
|
|
|
Tick-borne (endemic) Relapsing Fever |
Gram-negative Bacteria |
|
|
|
Louse-borne (epidemic) Relapsing Fever |
|
Yersinia pestis (plague ) |
|
|
Leptospirosis (military prophylaxis) |
|
Francisella tularensis (tularemia) + streptomycin |
|
Balantidium coli |
|
Campylobacter fetus |
|
|
Gram-negative Bacteria |
|
Leptotrichia buccalis (Vincent’s infection) |
|
|
|
Brucellosis (with streptomycin or gentamicin) |
|
Chancroid |
|
|
Bartonella bacilliformis |
|
Spirillum minus (rat-bite fever) |
|
|
Calymmatobacterium granulomatis |
|
Streptobacillus moniliformis (Haverhill fever) |
|
|
Vibrio cholerae (tetracycline) |
|
Pasteurella multocida |
|
|
Vibrio vulnificus (tetracycline + aminoglycoside) |
|
Pertussis |
|
|
Pseudomonas pseudomallei (meliodosis) + chloramphenicol |
|
Legionella pneumophilia |
|
|
Pseudomonas mallei (glanders) + streptomycin |
Gram-positive Bacteria |
|
|
|
Neisseria meningitidis prophylaxis (minocycline) |
|
Listeria monocytogenes (anthrax) |
|
Acne vulgaris |
|
Clostridium perfringens and tetani |
|
|
Urethral syndrome, acute |
|
Actinomycosis |
|
|
Epididymitis, acute (sexually transmitted) |
|
Nocardiosis |
|
|
Pelvic inflammatory disease |
Chronic bronchitis |
||
|
Urethritis, nonspecific |
|
|
|