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

Table 55–1
Structural Formulas of the Tetracyclines
O
OH O OH O
10
OH
C NH 11
9
1 2
12 2
8
6 5 4 3
7
OH
CH3
OH
N(CH3 ) 2
TETRACYCLINE
CONGENER SUBSTITUENT(S) POSITION(S)
Chlortetracycline –Cl 7
Oxytetracycline –OH,–H 5
Demeclocycline –OH,–H; –Cl 6; 7
Methacycline –OH,–H; CH 2
5; 6
Doxycycline –OH,–H; –CH 3
, –H 5; 6
Minocycline –H,–H; –N(CH 3
) 2
6; 7
to tetracycline versus 40% in the Asia-Pacific region (Hoban et al.,
2001). Bacillus anthracis and Listeria monocytogenes are susceptible.
Of note, the tetracyclines, doxycycline and minocycline in particular,
have generally retained excellent levels of activity against
staphylococci, including methicillin-resistant Staphylococcus aureus
(MRSA). Doxycycline and minocycline can be active against some
tetracycline-resistant isolates.
H. influenzae is generally susceptible, but many
Enterobacteriaceae have acquired resistance. Although all strains of
Pseudomonas aeruginosa are resistant, 90% of strains of Burkholderia
pseudomallei (the cause of melioidosis) are sensitive. Most strains of
Brucella also are susceptible. Tetracyclines remain useful for infections
caused by Haemophilus ducreyi (chancroid), Vibrio cholerae and
V. vulnificus, and inhibit the growth of Legionella pneumophila,
Campylobacter jejuni, Helicobacter pylori, Yersinia pestis, Yersinia
enterocolitica, Francisella tularensis, and Pasteurella multocida.
Strains of Neisseria gonorrhoeae no longer are predictably susceptible
to tetracycline, which is not recommended for treatment of gonococcal
infections. The tetracyclines are active against many anaerobic
and facultative microorganisms. A variable number of anaerobes (e.g.,
Table 55–2
Activity of Selected Antimicrobials Against Key Gram-positive Pathogens
CONCENTRATION OF ANTIMICROBIAL AGENT REQUIRED TO INHIBIT GROWTH OF 90% OF ISOLATES, μg/mL
(% SUSCEPTIBLE AT CLINICALLY ACHIEVABLE CONCENTRATIONS OF DRUG)
Streptococcus Staphylococcus
Streptococcus
Pneumoniae
Aureus
Enterococcus Enterococcus
Pyogenes PCN-S PCN-R MSSA MRSA Faecalis Faecium
Tetracycline 4 ≤2 >8 ≤2 ≤2 >8 >8
(89.7) (94.6) (36.7) (95.7) (93.4) (24.6) (58.7)
Tigecycline ≤0.03 ≤0.03 ≤0.03 0.25 0.25 0.25 0.12
(100) (NR) (NR) (100) (99.9) (99.9) (NR)
Erythromycin 1 >2 >2 >2 >2 >2 >2
(89.7) (87.3) (17.2) (70.8) (6.1) (9.1) (3.0)
Clindamycin ≤0.25 ≤0.25 >2 ≤0.25 >2 NA NA
(97.7) (97.1) (44.4) (94.6) (57.9)
Quinupristin/ ≤0.12 0.5 0.5 0.25 0.5 8 2
dalfopristin (100) (99) (100) (100) (100) (3.9) (92.6)
Linezolid 1 1 1 2 2 2 2
(100) (100) (100) (99.9) (99.9) (99.9) (98.0)
Vancomycin 0.25 ≤1 ≤1 1 1 2 >16
(100) (100) (100) (99.9) (99.9) (94.5) (26.6)
Daptomycin 0.06 0.12 0.12 0.25 0.5 2 4
(100) (NA) (NA) (100) (100) (100) (100)
Entries are drug concentrations, in μg/mL, required to inhibit growth of 90% of isolates of that organism. In parentheses below each drug concentration
is the percentage of isolates inhibited at clinically useful drug concentrations. PCN-S = penicillin-susceptible; PCN-R = penicillin-resistant; MSSA =
methicillin-susceptible Staphylococcus aureus; MRSA = methicillin-resistant Staphylococcus aureus; NR = not reported; NA = not applicable.
Sources: Gales et al., 2008; Critchley et al., 2003.