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US4911924A
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Induction of antibiotic hypersensitivity in tetracycline-resistance microorganisms
Assignee: University of New Mexico
•
Filing: 1987-04-17
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Granted: 1990-03-27
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Expires: 2007-04-17
Abstract
Abstract Microorganisms carrying tetracycline-resistant determinants are hypersensitized to Sm- and 2-DOS- aminoglycoside antibiotics by exposure to subinhibitory amounts of tetracycline inducer.
Inventors
- 👤 Jeffrey K. Griffith
- 👤 William L. Anderson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 04:00
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/65; Y; Y02; Y02A; Y02A50/00; Y02A50/30
Claims Analysis
Total Claims: 56
Claim 1
Independent Claim
70 words
A method for hypersensitizing a microorganism carrying a tetracycline-resistant determinant to a therapeutic antibiotic containing at least one streptamine or 2-deoxystreptamine functional group, comprising first exposing the microorganism to a subinhibitory concentration of a tetracycline inducer in an amount and for a period of time sufficient to induce expression of tetracycline resistance and to hypersensitize the microorganism to the therapeutic antibiotic and thereafter exposing the microorganism to the therapeutic antibiotic.
Claim 2
Independent Claim
70 words
A method for hypersensitizing a microorganism carrying a tetracycline-resistant determinant to a therapeutic antibiotic containing at least one streptamine or 2-deoxystreptamine functional group, comprising first exposing the microorganism to a subinhibitory concentration of a tetracycline inducer in an amount and for a period of time sufficient to induce expression of tetracycline resistance and to hypersensitize the microorganism to the therapeutic antibiotic and thereafter exposing the microorganism to the therapeutic antibiotic.
Claim 3
Dependent Claim
11 words
The method of claim 1, wherein the microorganism is a bacteria.
Claim 4
Dependent Claim
12 words
The method of claim 2, wherein the microorganism is a Gram-negative bacteria.
Claim 5
Dependent Claim
21 words
The method of claim 1, wherein the microorganism is resistant to a tetracycline serum concentration of at least about 12.5 ug/ml.
Claim 6
Dependent Claim
21 words
The method of claim 4, wherein the microorganism is resistant to a tetracycline serum concentration of at least about 16 ug/ml.
Claim 7
Dependent Claim
21 words
The method of claim 5, wherein the microorganism is resistant to a tetracycline serum concentration of at least about 50 ug/ml.
Claim 8
Dependent Claim
19 words
The method of claim 1, wherein the subinhibitory concentration is less than about one-half the minimum inhibitory serum concentration.
Claim 9
Dependent Claim
19 words
The method of claim 4, wherein the subinhibitory concentration of tetracycline inducer employed is less than about 4 ug/ml.
Claim 10
Dependent Claim
15 words
The method of claim 8, wherein the subinhibitory concentration is less than about 2 ug/ml.
Claim 11
Dependent Claim
15 words
The method of claim 9, wherein the subinhibitory concentration is less than about 1 ug/ml.
Claim 12
Dependent Claim
13 words
The method of claim 1, wherein the therapeutic antibiotic is an aminoglycoside antibiotic.
Claim 13
Dependent Claim
16 words
The method of claim 1, wherein the therapeutic antibiotic is kanamycin, amikacin, gentamicin, tobramicin, or streptamicin.
Claim 14
Dependent Claim
11 words
The method of claim 12, wherein the therapeutic antibiotic is kanamycin.
Claim 15
Dependent Claim
11 words
The method of claim 1, wherein the tetracycline inducer is antimicrobially-active.
Claim 16
Dependent Claim
18 words
The method of claim 1, wherein the tetracycline inducer is tetracycline, chlortetracycline, xytetracycline, demeclocycline, methacycline, doxycycline, or minocycline.
Claim 17
Dependent Claim
12 words
The method of claim 1, wherein the tetracycline inducer is antimicrobially inactive.
Claim 18
Dependent Claim
14 words
The method of claim 1, wherein the tetracycline inducer is tetracycline or acid-inactivated tetracycline.
Claim 19
Dependent Claim
22 words
The method of claim 1, wherein the tetracycline inducer contains a tetracycline nucleus and is substantially non-toxic at the dosage levels employed.
Claim 20
Dependent Claim
10 words
The method of claim 2, wherein the inducer is tetracycline.
Claim 21
Independent Claim
87 words
A method for treating a mammal infected with a tetracycline-resistant microorganism comprising: (a) first administering to the mammal an amount of tetracycline inducer sufficient to obtain a serum concentration of tetracycline inducer subinhibitory to the infecting microorganism and also sufficient to hypersensitize the microorganism to a therapeutic antibiotic containing at least one streptamine or 2-deoxystreptamine functional group; and (b) thereafter administering an amount of the therapeutic antibiotic sufficient to provide a serum concentration thereof which is at least a minimum inhibitory serum concentration for the hypersensitized microorganism.
Claim 22
Independent Claim
87 words
A method for treating a mammal infected with a tetracycline-resistant microorganism comprising: (a) first administering to the mammal an amount of tetracycline inducer sufficient to obtain a serum concentration of tetracycline inducer subinhibitory to the infecting microorganism and also sufficient to hypersensitize the microorganism to a therapeutic antibiotic containing at least one streptamine or 2-deoxystreptamine functional group; and (b) thereafter administering an amount of the therapeutic antibiotic sufficient to provide a serum concentration thereof which is at least a minimum inhibitory serum concentration for the hypersensitized microorganism.
Claim 23
Dependent Claim
34 words
The method of claim 20, wherein the microorganism is resistant to a subinhibitory serum concentration of tetracycline inducer of at least about 50ug/ml, and the serum concentration of inducer is less than about 50ug/ml.
Claim 24
Dependent Claim
11 words
The method of claim 20, wherein the therapeutic antibiotic is gentamicin.
Claim 25
Dependent Claim
11 words
The method of claim 20, wherein the mammal is a human.
Claim 26
Dependent Claim
11 words
The method of claim 20, wherein the microorganism is a bacteria.
Claim 27
Dependent Claim
12 words
The method of claim 24, wherein the microorganism is a Gram-negative bacteria.
Claim 28
Dependent Claim
21 words
The method of claim 20, wherein the microorganism is resistant to a tetracycline serum concentration of at least about 12.5 ug/ml.
Claim 29
Dependent Claim
21 words
The method of claim 26, wherein the microorganism is resistant to a tetracycline serum concentration of at least about 16 ug/ml.
Claim 30
Dependent Claim
21 words
The method of claim 27, wherein the microorganism is resistant to a tetracycline serum concentration of at least about 50 ug/ml.
Claim 31
Dependent Claim
27 words
The method of claim 20, wherein the subinhibitory serum concentration of tetracycline inducer obtained is less than about one-half the minimum inhibitory serum concentration for the microorganism.
Claim 32
Dependent Claim
15 words
The method of claim 20, wherein the subinhibitory concentration is less than about 4 ug/ml.
Claim 33
Dependent Claim
15 words
The method of claim 30, wherein the subinhibitory concentration is less than about 2 ug/ml.
Claim 34
Dependent Claim
15 words
The method of claim 3-, wherein the subinhibitory concentration is less than about 1 ug/ml.
Claim 35
Dependent Claim
13 words
The method of claim 20, wherein the therapeutic antibiotic is an aminoglycoside antibiotic.
Claim 36
Dependent Claim
15 words
The method of claim 33, wherein the antibiotic is kanamycin, amikacin, gentamicin, tobramicin, or streptomicin.
Claim 37
Dependent Claim
10 words
The method of claim 34, wherein the antibiotic is kanamycin.
Claim 38
Dependent Claim
10 words
The method of claim 20, wherein the inducer is antimicrobially-active.
Claim 39
Dependent Claim
18 words
The method of claim 20, wherein the tetracycline inducer is tetracycline, chlortetracycline, oxytetracycline, demeclocycline, methacycline, doxycycline, or minocycline.
Claim 40
Dependent Claim
12 words
The method of claim 20, wherein the tetracycline inducer is antimicrobially inactive.
Claim 41
Dependent Claim
14 words
The method of claim 20, wherein the tetracycline inducer is tetracycline or acid-inactivated tetracycline.
Claim 42
Dependent Claim
22 words
The method of claim 20, wherein the tetracycline inducer contains a tetracycline nucleus and is substantially non-toxic at the dosage levels employed.
Claim 43
Dependent Claim
11 words
The method of claim 24, wherein the tetracycline inducer is tetracycline.
Claim 44
Dependent Claim
51 words
The method of claim 23, wherein the microorganism is a Gram-negative bacteria resistant to a tetracycline serum concentration of at least about 50 ug/ml and the tetracycline inducer is administered in an amount sufficient to provide a subinhibitory serum concentration of inducer of less than about half the minimum inhibitory concentration.
Claim 45
Dependent Claim
17 words
The method of claim 42, wherein tetracycline inducer is tetracycline, chlortetracycline, oxytetracycline, demeclocyline, methacycline, doxycycline, or minocycline.
Claim 46
Dependent Claim
13 words
The method of claim 42, wherein the therapeutic antibiotic is an aminoglycoside antibiotic.
Claim 47
Dependent Claim
12 words
The method of claim 23, wherein the therapeutic is an aminoglycoside antibiotic.
Claim 48
Dependent Claim
16 words
The method of claim 42, wherein the therapeutic antibiotic is kanamycin, amikacin, gentamicin, tobramicin, or streptamicin.
Claim 49
Dependent Claim
16 words
The method of claim 43, wherein the therapeutic antibiotic is kanamycin, amikacin, gentamicin, tobramicin, or atreptamicin.
Claim 50
Dependent Claim
11 words
The method of claim 46, wherein the therapeutic antibiotic is kanamycin.
Claim 51
Dependent Claim
11 words
The method of claim 20, wherein the therapeutic antibiotic is kanamycin.
Claim 52
Dependent Claim
14 words
The method of claim 49, wherein the tetracycline inducer is tetracycline or acid-inactivated tetracycline.
Claim 53
Dependent Claim
11 words
The method of claim 1, wherein the therapeutic antibiotic is gentamicin.
Claim 54
Dependent Claim
11 words
The method of claim 46, wherein the therapeutic antibiotic is gentamicin.
Claim 55
Dependent Claim
11 words
The method of claim 51, wherein the tetracycline inducer is tetracycline.
Claim 56
Dependent Claim
11 words
The method of claim 52, wherein the tetracycline inducer is tetracycline.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-03-26 | 1993-09-25 | 1994-03-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-03-26 | 1997-09-25 | 1998-03-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-03-26 | 2001-09-25 | 2002-03-27 | $7700.00 | Window Closed / Lapsed |