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동물 및 환경에서 분리된
항생제 내성균 및 내성 유전자
경북 의대 미생물학 조동택
The antibiotic paradox :
How miracle drugs are destroying the miracle?
In Humans
In Fish
In Other Animals
In Plants
Non-Human Antimicrobial Use in USATotal Percent Pounds Total Use
Livestock Uses
Non-therapeutic (3 species*) 24,600,000 70.0%
Non-therapeutic (other) 3,000,000 8.5%
Therapeutic (all species) 2,000,000 5.7%
Pesticide Uses 50,000 0.1%
Companion Animals 1,000,000 2.8%
Total Non-Human Uses 30,600,000 87.0%
Human Use 4,500,000 13.0%
Total Use 35,100,000
101st Annual Meeting, American Society for MicrobiologyMay 22, 2001, Charles M. Benbrook
* 3 species: cattle, swine, poultry
Usage of antimicrobial agents for food animals in Europe
Basic & Clinical Pharmacology & Toxicology96:271-334
Relative distribution of usage of antimicrobial agents for treatment of infections in pigs and
humans in Denmark (from DANMAP 2004)
Basic & Clinical Pharmacology & Toxicology96:271-334
Changes in occurrence of resistance in E. faecium and E. faecalis isolated from Danish pigs or broilers from 1995 to 2003 following withdrawing of antimicrobial agents for growth promotion(Aarestrup et al. 2001; DANMAP 2004)
Basic & Clinical Pharmacology & Toxicology96:271-334
Agricultural Use of Antibiotics
significant source of antibiotic resistance
among foodborne pathogens
Consumers risk exposure to disease-carrying bacteria during food preparation and consumption. If serious food-borne illnesses occur, antibiotics used for treatment may not be effective if the bacteria have become resistant.
A Dangerous Cycle
Many of the same antibiotics humans are regularly added to livestock feed to promote rapid growth.
Slaughter and processing may result in bacterial contamination of retail foods.
Because of routine antibiotic use, strains of bacteria can form that are resistant to the drugs.
New Drug-Resistant SalmonellaS. typhimurium DT104
살모넬라 균주중 S. typhimurium DT104 균주는 최근에 전세계적으
로 유행하고 있는 대표적인 균주로 ampicillin, chloramphenicol, streptomycin, sulfonamide 및 tetracycline 등 5종의 항생제에 내
성을 나타내며 다른 살모넬라균에 비하여 질병의 이환률과 사망률이 높
은 것으로 알려져 있다.
Swine Herd
Swine Herd
Slaughter-house
PorkProducts
Consumers Hospital
Two herds were identified as sources of Salmonella DT104. Piglets were moved between farms and the farms shared machinery.
Eighteen people became ill after eating contaminated fork and seven were hospitalized; half ate meat confirmed coming from the incriminated slaughter house. A slaughterhouse worker also fell ill.
Two additional people – a nurse and a fellow patient who shared a hospital room – were infected after contact with one of the hospitalized patients. The fellow patient died.
Nurse
Fellow patient
Worker
The Community
Outbreak of a Resistant Foodborne IllnessOutbreak in Denmark of Salmonella DT104
Using molecular “fingerprinting” technique, researchers in Denmark were able to reconstruct the course of the 1998 Salmonella DT104 outbreak from the farm through the community.
Detection of PSE in Salmonella entericaserotype Typhimurium DT104 from pig
1. 서울 근교 도축장에서 총 152마리의 돼지에서 10주의 Salmonella 분리
Salmonella enterica serovar TyphimuriumSa 10
Salmonella typhimuriumSa 9
Salmonella typhimurium LT2Sa 8
Salmonella typhimuriumSa 7
Salmonella enterica serovar TyphimuriumSa 6
Salmonella enterica serovar TyphimuriumSa 5
Salmonella typhimurium LT2Sa 4
Salmonella typhimuriumSa 3
Salmonella typhimuriumSa 2
Salmonella enterica serovar TyphimuriumSa 1
동 정 결 과 (by 16S rRNA sequencing)Strains
S. ardwickC1 Sa 10
S. ardwickC1Sa 9
S. muenchenC2Sa 8
DT203S. typhimuriumBSa 7
S. ardwickC1 Sa 6
S. ardwickC1Sa 5
DT104LS. typhimuriumBSa 4
S. bradenburgBSa 3
S. ardwickC1Sa 2
S. ardwickC1 Sa 1
Phage type 균 주 판 정O-serogroup균 주 번 호
2. Phage typing
S19S21S23S26S26CCARM11066
R-S24S17S22S22Sa10
R-S22S17S23S24Sa 9
R-R-R11S26R-Sa 8
R-R-R-R-R-Sa 7
R-S24S18S24S25Sa 6
R-S24S17S25S23Sa 5
R-R-R-R-R-Sa 4
R -S22S17S26S22Sa 3
R-S20S17 S23S24Sa 2
R-S21S17S24S23Sa 1
TetracyclineSulfisoxazolStreptomycinChloram-phenicolAmpicillinStrains
3. Antimicrobial susceptibility by disk diffusion method (지름 mm)
116244E.coli
128128482Sa10
128128482Sa 9
> 128> 1024164> 128Sa 8
> 128> 1024> 128> 128> 128Sa 7
128128482Sa 6
128128482Sa 5
> 128> 102464> 128> 128Sa 4
12864884Sa 3
128128482Sa 2
128128482Sa 1
TetracyclineSulfisoxazoleStreptomycinChloramphenicolAmpicillin
4. Antimicrobial susceptibility test by agar dilution method (MIC)
5. Characterization of β-lactamase
with Isoelectric focusing, PCR, and sequencing
DT104 균주에서 PSE-1 β-lactamase 유전자가 확인
Antibiotic-resistant bacteria and antibiotics are discharged in huge amount in the environment as a result of the increasing and often indiscriminate use of antibiotics in medical, veterinary, and agricultural practices. River waters are the main receptacle for these pollutants, since they receive the sewage of urban effluents. As rivers are one of the major sources of water, directly or indirectly, for human and animal consumption, this pollution may contribute to the maintenance and even the spread of bacterial antibiotic resistance.
River water : main receptacle for pollutants
강물에 존재하는 총 균 수와 장내 세균수
총균수
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
10th
11th
12th
13th
14th
15th
16th
17th
18th
19th
20th
21st
22nd
23rd
24th
25th
26th
27th
28th
29th
30th
31st
32nd
log CFU/ml
중랑천
한강
금호강
낙동강
섬진강 지류
섬진강
KONAR, 2005
Norfloxacin 내성 대장균수
0
50
100
150
200
250
300
10th
11th
12th
13th
14th
15th
16th
17th
18th
19th
20th
21st
22nd
23th
24th
25th
26th
27th
28th
29th
30th
31st
32nd
CFU
/m
중랑천 NOR내성 장내세균수
중랑천 NOR내성 대장균수
한강 NOR내성 장내세균수
한강 NOR내성 대장균수
금호강 NOR내성 장내세균수
금호강 NOR내성 대장균수
낙동강 NOR내성 장내세균수
낙동강 NOR내성 대장균수
섬진지류 NOR내성 장내세균수
섬진지류 NOR내성 대장균수
섬진강 NOR내성 장내세균수
섬진강 NOR내성 대장균수
항생제 내성 장내 세균 및 대장균 수
KONAR, 2005
Identification of CTX-M-14, TEM-52, and CMY-1 extended-spectrum β-lactamases
in environmental strains of E. coli isolated from Han river in Korea
ApTcSmSuTpKmGm32482512>12810022
ApTcSmSuTpKmGm32482256>12810020
ApCmTcSmSuTpKmGmAk32482256>12810019
ApTcSmSuTpKmGm3248264>12810018
ApTcSmSuTpKmGm3248264>12810016
ApCmTcSmSuTpKmGm>128882512>12810014
ApTcSmSuTpKmGm32>512416256>12810013
ApCmTcSmSuTpKmGm32884256>12810012
ApCmTcSmSuTpKmGm32882512>12810011
ApCmTcSmSuTpKmGm32884512>12810010
ApCmTcSmSuTpKmGmAk>1284162128>12810009
ApCmTcSmSuTpKmGmAk<0.54481612810006
ApCmTcSmSuTpKmGmAk<0.58481612810005
ApCmTcSmSuTpKmGm<0.5448166410004
ApCmTcSmSuTpKmGm<0.58481612810003
ApCmTcSmSuTpKmGm<0.58481612810001
Antimicrobial resistance patternbnorfloxacincefoxitinaztreonamceftazidimecefotaximecephalothin
Strain No.
MICs (µg/ml)a
Antimicrobial susceptibility of E. coli isolated from Han river
KONAR, 2005
dfrA17-aadA51.6 kbTEM-1, CTX-M145.4, 8.0+10014
dfrA12-orfF-aadA22kbCTX-M148.0+10022
dfrA12-orfF-aadA22kbCTX-M148.0+10020
dfrA12-orfF-aadA22kbCTX-M148.0+10019
dfrA12-orfF-aadA22kbCTX-M148.0+10018
dfrA12-orfF-aadA22kbCTX-M148.0+10016
NDdNDdTEM-1, CMY-1, OXA-1-like5.4, 7.4, 8.0+10013
dfrA17-aadA51.6 kbTEM-1, CTX-M145.4, 8.0+10012
dfrA17-aadA51.6 kbTEM-1, CTX-M145.4, 8.0+10011
dfrA17-aadA51.6 kbTEM-1, CTX-M145.4, 8.0+10010
ND2.1kb, 1.4kbTEM-1, CTX-M145.4, 8.0+10009
aadA11kbTEM-1, TEM-52, OXA-1-like5.4, 5.9, 7.4+10006
aadA11kbTEM-1, TEM-52, OXA-1-like5.4, 5.9, 7.4+10005
aadA11kbTEM-1, TEM-52, OXA-1-like5.4, 5.9, 7.4+10004
aadA11kbTEM-1, TEM-52, OXA-1-like5.4, 5.9, 7.4+10003
aadA11kbTEM-1, TEM-52, OXA-1-like5.4, 5.9, 7.4+10001
integrated gene cassettessize of ampliconcβ-lactamase genesIsoelectric point (pI) DDSTaStrain No.
Class I integron
Genotypic characteristics of E. coli isolated from Han river
KONAR, 2005