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resistance in bacteria
Virus
Bacteria
Parasites
Fungus
Virus:
Bacteria
Mountain streams
Ocean water
Rotting animal or plant
Sewer
Topsoil
Blood/skin/throat/lungs/urinary bladder/intestine
Diseases Caused by
Viruses and Bacteria
Virus
Common cold
Diarrhea (99%)
Acute Bronchitis
Influenza (flu)
Measles
Chicken Pox
AIDS
Rabies
Hepatitis
Bacteria
Urine infections
Strep Throat
Boils/abscesses
Gangrene
Some pneumonia
Ear infections (half)
Sinus infections (< half)
Bubonic Plague
Tuberculosis
Fact
Bacteria are the cause of the
vast majority of deaths due to
infection in the United States:
sepsis, meningitis, pneumonia
Fact
Most viral infections get better
all by themselves in 1-3 weeks;
no medications are required:
colds, flu, stomach virus
% Patients
Resolution of Acute
Bronchitis
100
No Antibiotic
80
(+) Antibiotic
60
40
20
0
0
10
12
14
16
18
need one
Patients have been trained to expect them
Doctors think the antibiotics will prevent a
secondary bacterial infection (theyre wrong)
They misdiagnose a viral infection for a
bacterial infection: Sinusitis vs Cold
HISTORICAL PERSPECTIVE
Antibiotics introduced 60 years ago
Bacteria from pre-antibiotic era had
Polyenes; Polymyxin
Tetracyclines; Chloramphenicol
Rifampicin; Chloroquine
Sulphamethoxazole
Penicillin; Vancomycin
penicillin works by blocking the formation of peptide bonds in
the bacterial cell wall and thereby weakens it, leaving the
bacterium susceptible to osmotic lysis
Emergence of Antimicrobial
Resistance
Susceptible Bacteria
Resistant Bacteria
Mutations
XX
Bacterial Resistance
Mechanisms
Decreased entry
Efflux pump
Altered target site
Mechanisms of Resistance
Enzymatic
degradation
Bypass pathway
Resistance Mechanisms
Inside the Bacterial Cell
Efflux Pumps
Hydrolysis
Reduced Uptake
Sequestering
Enzymatic Modification
Method of resistance
Chloramphenicol
Tetracycline
-lactams, Erythromycin
hydrolysis
Aminoglycosides, Chloramphenicol,
Fosfomycin, Lincomycin
inactivation of antibiotic by
enzymatic modification
Sulfonamides, Trimethoprim
Sulfonamides, Trimethoprim
Bleomycin
Chronology of Development of
Antibiotic Resistance
Antibiotic
Penicillin
Streptomycin
Tetracycline
Erythromycin
Gentamicin
Vancomycin
1942
1947
1956
1956
1970
1987
Resistance:
The World 2000
more investigations
more expensive, toxic antimicrobials required
expensive barrier nursing, isolation, procedures, etc.
third-world countries
some
antibiotic pressure
Need to use more costly and toxic agents
The emergence of untreatable pathogens
Penicillin-resistant
[1950s]
S. aureus
Methicillinresistant
[1970s]
S. aureus (MRSA)
[1997]
Vancomycin
[1990s]
Vancomycin-
resistant
S. aureus
[ 2002 ]
Vancomycin
intermediateresistant
S. aureus
(VISA)
Vancomycin-resistant
enterococci (VRE)
Emergence of Vancomycin
Resistant Enterococci
Non-Intensive Care Unit Patients
Intensive Care Unit Patients
Development of of Resistance in
Gram
Positive Pathogens
100
90
80
70
60
50
40
30
20
10
1975
VRE2
GISA3
1980
1985
1990
Year
1995
1996
VRSA4
2000
2002
Smith TL et al. N Engl J Med. 1999;340:493-501. 2Martone WJ. Infect Control Hosp Epidemiol. 1998;19:539-545.
3
Hiramatsu K et al. J Antimicrob Chemother. 1997;40:135-136. 4CDC. MMWR Morb Mortal Wkly Rep. 2002;51:565-567.
1
needed
Prevents infectious diseases
Facilitates confinement housing
Lowers costs
ANTIMICROBIAL RESISTANCE:
The role of animal feed antibiotic additives
No. Approved
Agents
1991
20
1992
1993
Piperacillin/Tazobactam
1994
1995
Dirithromycin, ceftibutin
1996
1997
Grepafloxacin, Trovafloxacin
1998
Rivaled 1994
1999
2000
Linezolid
2001
Ertapenem, ceftidoren
2002
2003
Daptomycin, gemifloxacin
Multiple agents
INDONESIA
AMRIN Study (The Antimicrobials
Resistance Watch)
Antibiotic Policy in hospitals
Waiting Room
Poster