ОСОБЕННОСТИ БЕТА-ЛАКТАМАЗНОЙ АКТИВНОСТИ

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, 2009,
8,
3
,
,
.,
.,
.,
.
«
»
.
;
,
.
(
.
., 2009).
,
,
, ,
,
.
35
, 42
,6
,5
,
2008/09
.
(A.
Menashi, 1988).
(
Sigma).
88,6% (95%
: 78,0-99,1)
,
20
23,5%
.
1
16,9%
, 2009,
8,
3
83,3% (95%
: 72,1-94,6),
28,7%
21,1%
.
100%
,
43,3%,
– 32,5%,
,
.
,
,
–
.
,
,
,
( ,
,
)
.
:
,
,
,
,
,
,
.
Abstract. Antibiotic resistance of pathogenic bacteria is known to be one of the most
challenging problems of up-to-date infectiology, but this phenomenon is still analyzed
from the position of bacteria only.
The other day we described the relatively high beta-lactamase activity of blood serum
of patients ill with erysipelas and pneumonia (I. Zhyltsou et al., 2009). Thus, the goal of
our present study was to confirm that blood serum of patients with other communicable
diseases also can destroy beta-lactams, and, besides, to assess frequency and level of
above activity. We examined 35 patients with adenoviral infection, 42 patients with acute
purulent tonsillitis, 6 patients with serous meningitis and 5 patients with purulent
meningitis who were hospitalized to Vitebsk Regional Infectious Hospital in 2008-09. To
determine the presence and level of beta-lactamase activity of blood serum, we used
2
, 2009,
8,
3
adjusted neocuproine technique (A. Menashi, 1988), ampicillin and penicillin G
(chemically pure substances by Sigma) were taken as substrates.
Beta-lactamase activity was found in 88,6% (95% CI: 78,0-99,1) of all patients ill
with adenoviral infection (average levels of antibiotic destruction for 20 minutes of
incubation were 23,5% for ampicillin and 16,9% for penicillin G).
Also, beta-lactamase activity was revealed in 83,3% of acute purulent tonsillitis cases
(95% CI: 72,1-96,4); middle level of antibiotic destruction was found equal to 28,7% for
ampicillin and 21,1% for penicillin G.
In patients with serous and purulent meningitis beta-lactamase activity of blood was
found in 100% of all cases; its corresponding middle level of destruction was 43,3% for
ampicillin and 32,5% for penicillin G what was found to be reliably higher than the same
characteristics of other investigated groups of patients.
We have also revealed several reliable direct correlations of moderate power between
the level of blood beta-lactamase activity on the one hand and both duration of
hospitalization and prescription of beta-lactams on the other hand.
Thus, our assumption that beta-lactamase activity is very common in human
population and can be found in patients ill with a number of diseases (perhaps, also in
normal healthy individuals) and it’s a response of the organism towards the prescription of
beta-lactams has been once again confirmed.
Keywords: Beta-lactamase activity, human blood serum, adenoviral infection, acute
purulent tonsillitis, serous meningitis, purulent meningitis, antibiotics of beta-lactam
group.
27,
:
,
, 210023, .
«
,
,
»,
. 24-33-46 -
.
.
−
(
3
)
, 2009,
8,
3
.
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33,82%
G1, 2
4,
-
(
) [1].
,
(«
»),
[2].
,
,
90-
.
,
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(
19
96%
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(
)
–
[3].
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D-
(
12).
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-D-
-D–
);
D-
-D-
D-
;
(
[4]),
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4
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, 2009,
8,
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killing
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[5].
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[5].
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– 0,5-1
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) [6].
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10.000
1000-4000
);
5-10
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[5].
,
,
.
,
,
[7].
,
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,
3-
5
, 2009,
8,
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3-
,
)
;
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,
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3-
,
,
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,
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[8].
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(
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[9].
(
, (±)-2-
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BCL-98)
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,
L-
;
[10].
(
,
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,
.
,
in vivo
in vitro,
.
«
»
[11].
,
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6
, 2009,
8,
3
,
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-
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(
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(
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1.
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3000
15
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2.
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[12].
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SOLAR.
03 11 2864 06)
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7
2203, (
.
, 2009,
8,
3
(
Sigma).
0,05
0,18
1:1
(t=37° )
20
.
0,4
(pH=4,75), 0,5
30
.
454,5
10
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:
1)
(
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0,05
1:1,
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2)
(
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3)
(
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30
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,
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(
).
.
,
:
)
;
.
8
)
,
, 2009,
8,
3
,
3
.
,
.
3.
.
–
(cross-
sectional;
).
4.
,
88
(
)
2008-2009
,
.
4
:
1. 35
«
2. 42
»;
«
3. 6
«
4. 5
«
»;
»;
».
,
1.
1
,
n (%)
88
-
35
42
6
5
( )
21,6
min 12, max 62
95%
: 19,6-23,6
20,4
min 13, max 62
95%
: 16,9-24,0
21,2
min 12, max 44
95%
: 18,9-23,6
25,5
min 13, max 51
95%
: 11,2-39,8
28,6
min 14, max 45
95%
: 13,3-43,9
,
n (%)
40
(45,5)
( )
22,0
min 12, max 51
95%
: 18,8-25,1
18,8
min 13, max 27
95%
: 15,9-21,7
21,0
min 12, max 44
95%
: 17,1-25,0
27,5
min 13, max 51
95%
: 0,3-54,7
38,5
min 32, max 45
11
(31,4)
23
(54,8)
4
(66,7)
2
(40,0)
9
,
n (%)
48
(54,5)
24
(68,6)
19
(45,2)
2
(33,3)
3
(60,0)
( )
21,3
min 13, max 62
95%
: 18,6-24,1
21,2
min 13, max 62
95%
: 16,0-26,3
21,5
min 14, max 37
95%
: 18,9-24,1
21,5
min 20, max 23
95%
: 2,4-40,6
22,0
min 14, max 33
, 2009,
8,
1
,
20-25
3
,
1,2 : 1 (
)
1 : 2,2
);
,
(54,5%
45,5%,
).
.
21
(
- 9,
- 11,
56 -
- 1),
(
- 23,
- 28,
- 5),
- 2,
- 4),
6 1-
).
,
(66,7%, 95%
: 56,6-76,8)
;
(25,0%, 95%
: 15,7-34,3).
,
.
,
.
,
,
.
,
(12
5,5
(10
95%
–
., 95%
34,3%,
: 4,5-6,5),
- 29,4%,
5,9
: 3,9-7,9),
–
5,2
(2
(9
., 95%
),
10
– 26,5%,
: 3,3-7,1).
(4
.,
,
),
(3
, 2009,
8,
3
),
(2
),
(1
).
6,1
: 5,5-6,7).
. (95%
– 1 (n=32),
– 0 (n=24).
,
.
(n=27, 69,2%,
5,9
: 5,0-6,8),
., 95%
(n=7, 17,9%,
5,4
., 95%
(
: 3,9-6,9),
n=6, 15,4%;
4,2
4,8
., 95%
., 95%
: 2,0-6,3;
: 2,1-7,5).
(n=1),
,
(n=4)
(n=2).
7,5
6,9-8,1).
. (95%
:
- 1 (n=36),
– 0 (n=23).
,
,
.
(n=4,66,7%)
11,0
(n=1)
., 95%
: 3,2-18,8).
(n=1).
9,4
. (95%
: 2,5-16,3).
– 1 (n=6),
– 0 (n=6).
(n=2),
(n=2),
(n=2),
(n=1),
(n=1),
(n=1),
(n=1),
(n=1).
18,3
11
.
, 2009,
(95%
8,
3
: 14,5-22,1).
–2
(n=3),
– 2 (n=3).
,
,
–
.
,
,
,
,
,
,
,
.).
5.
Statistica 7.0.
,
–
(Spearman),
– U(Mann-Whitney),
(>2)
–
(Kruskal-Wallis).
2
,
(< 10
)
-
(Fisher’s exact test).
,
;
.
,
(
2.
12
.
).
, 2009,
8,
3
2
,%
(95%
, %
,%
)*
(95%
87,5% (95%
80,6-94,4)
:
88,6% (95%
78,0-99,1)
:
83,3% (95%
72,1-94,6)
:
100%
100%
(95%
)**
28,0% (95%
:
24,75-31,27)
min 2,0, max 87,0
23,5% (95%
:
19,34-27,75)
min 2,0, max 42,3
28,7% (95%
:
23,39-34,06)
min 6,7, max 87,0
34,2% (95%
:
21,35-46,95)
min 17,7, max 43,7
43,3% (95%
:
26,36-60,32)
min 20,6, max 54,1
, %
)*
77,3% (95%
68,5-86,0)
:
74,3% (95%
59,8-88,8)
:
76,2% (95%
63,3-89,1)
:
83,3% (95%
53,5-100)
:
100%
(95%
)**
20,2% (95%
:
16,89-23,44)
min 1,4, max 88,2
16,9% (95%
:
15,78-26,32)
min 4,8, max 88,2
21,1% (95%
:
15,78-26,32)
min 4,8, max 88,2
18,9% (95%
:
0-43,39)
min 1,4, max 41,4
32,5% (95%
:
11,13-53,83)
min 13,0, max 59,3
:
*
** 1.
,
;
%
(20
)
,
; 2.
,
.
100
90
80
70
60
50
40
30
20
10
0
-10
1
13-
2
3
,2,4-
4
,
Median
25%-75%
Min-Max
.
. 1.
13
, 2009,
8,
3
100
90
80
70
60
50
40
30
20
10
0
-10
1
2
1-
3
,2,4-
3-
Median
25%-75%
Min-Max
4
,
. 2.
.
1-2
,
.
whisker» («
»),
« »
,
,
« »
«
– 3
«box-and-
(75
» – 1
),
,
–
(25
«
(
14
,
),
» –
.
).
,
, 2009,
8,
3
–
20-30%
.
,
;
.
,
–
,
.
–
0
88%.
,
,
(
74%
100%
).
2
( =0,28…1,0).
,
=0,018),
( =0,059).
U-
,
:
1)
,
( =0,034);
2)
,
,
( =0,0049
15
,
=0,0041
, 2009,
8,
3
)
( =0,018
,
0,020
).
3)
,
=0,10…0,92).
,
,
,
,
–
,
«
»
.
,
:
1.
(r=+0,62…
+0,66, p<0,0001).
,
[11];
2.
(r=+0,33, p<0,005)
(r=+0,27, p<0,05;
r=+0,37, p<0,05).
,
,
, ,
,
;
3.
(r=+0,30, p<0,01),
(r=+0,30, p<0,01).
(
r=+0,23, p<0,05).
16
, 2009,
8,
3
,
,
(
,
),
;
4.
(r=+0,75, <0,01).
,
,
,
.
,
,
,
,
,
(p)
(6
5
,
,
0,01
.
)
.
.
,
(
[11])
/
(r= +0,9…1,0, p<0,05)
.
,
,
(
,
,
88),
.
(
.
)
,
1)
,
:
5
17
,
, 2009,
2)
8,
3
,
1-1,5
4
(4-6
),
,
,
4-6
,
0,2-0,3
,
(0,18
).
,
28%
20%
(
20
37° )
(
2,5
)
,
:
(
),
,
(
)
,
,
,
.
3.1.
,
,
,
(
)
.
(
,
),
.
,
.
,
(
)
–
,
.
18
, 2009,
8,
3
3.2.
,
,
(
), ,
,
.
3.3.
,
.
,
,
,
( ,
,
)
.
,
[8]
.
,
,
,
in vivo
in vitro.
,
;
.
.
,
,
19
, 2009,
8,
3
.
1.
«
in vivo
/ . .
[
»
:
IgG,
.] //
. – 2006. –
5 (62). – . 46-48.
2. Jerne, N. K. Towards a network theory of the immune system / N. K. Jerne //
Ann.Immunol. (Inst.Pasteur). – 1974. – Vol. 125, N 1-2. – P. 373-389.
3. Bactericidal Killing Activities of Cefepime, Ceftazidime, Cefotaxime, and
Ceftriaxone against Staphylococcus aureus and
-Lactamase-Producing Strains of
Enterobacter aerogenes and Klebsiella pneumoniae in an In Vitro Infection Model /
M. Shirley Palmer [et al.] // Antimicrobial Agents And Chemotherapy. – 1995. – Vol. 39,
N 8. – P. 1764-1771.
4. Mechanism of penicillin action: Penicillin and substrate bind covalently to the
same active site serine in two bacterial D-alanine carboxypeptidases (B-lactam/
peptidoglycan/ membrane enzyme/ penicillinase/ acyl enzyme) / R. Rogers Yocum [et al.]
// Biochemistry. – 1979. – Vol. 76, N 6. – P. 2730-2734.
5. Blumberg, P. M. Interaction of Penicillin with the Bacterial Cell: PenicillinBinding Proteins and Penicillin-Sensitive Enzymes / M. Peter Blumberg, L. Jack
Strominger // Bacteriological Reviews. – 1974. – Vol. 38, N 3. – P. 291-335.
6.
, . .
/
. . .
.
, . .
.–
.:
, 2002. – 432 .
7. Livermore, D. M. B-lactams: mode of action and mechanisms of bacterial
resistance. In: Lorian V., editor. Antibiotics in laboratory medicine / D. M. Livermore,
J. D. Williams. – Baltimore: Williams & Wilkins, 1991. – P. 503-578.
8. Walter, E. Hydrolysis of 3-Acetoxymethyl Cephalosporins by Lysed WholeBlood
/ E. Walter Wright, A. Judith Frogge // Antimicrobial Agents And Chemotherapy. – 1980.
– Vol. 17, N 1. – P. 99-100.
20
, 2009,
8,
3
9. Moellering, R. C. The carbapenems: new broad spectrum beta-lactam antibiotics /
R. C. Moellering, G. M. Eliopoulos, D. E. Sentochnik // J. Antimicrob. Chemother. –
1989. – Vol. 24. – Suppl. A. – P. 1-7.
10. An investigation of the destruction of the beta-lactam ring of penems by the
albumin drug-binding site / H. Bruderlein [et al.] // Can. J. Biochem.– 1981. – Vol. 59
(10). – P. 857-866.
11.
/
. .
[
.]
//
.– 2009. – . 8,
1. – . 58-67.
12. Menashi, A. C. A colorimetric procedure for measuring b-lactamase activity /
A.C. Menashi, J. Abraham, A. M. Antone Menashi // Analitycal Biochemistry. – 1988. –
Vol. 168. – P. 252-258.
21
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