antibiotic pressure and resistance in bacteria
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Antibiotic Pressure and Resistance in Bacteria
Sarmistha B. Hauger M.D.Director, Pediatric Infectious Disease
Children’s Hospital of AustinAustin, Texas
TDH CA-MRSA Conference
September, 2004
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Antibiotic Pressure and Resistance in Bacteria
• What is it and why is it important?• How extensive is it?• How does it happen? • What factors promote the spread of
resistant bacteria ?• How does it pertain to the development of
CA-MRSA infections?• What can HCW do to curb this trend?
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Antibiotic Pressure and Resistance in Bacteria
What is it ?• ”Selection pressure of antibiotics has led to
the emergence of antibiotic-resistant bacteria.”
– Antibiotics can effect bacteria unrelated to the targeted infectious agent; these may be “normal” flora, leading to the emergence of resistant mutants inhabiting the same environment.
Baquero et al., International Report 1996;23:819
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Antibiotic Pressure and Resistance in BacteriaWhy is it important?
• Antibiotic resistance has developed in almost all classes of bacteria of pathogenic potential.
• Resistance in organisms of low virulence can emerge as important pathogens.
• The development of resistant bacteria has driven pharmaceutical research to develop more potent, broad-spectrum antibiotics.
• Use of these in turn, has fueled the appearance of bacteria with newer modes of resistance.
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Antibiotic Pressure and Resistance in BacteriaWhy is it important?
• Infections with resistant bacteria occur in health care settings AND the community.
• Examples of hospital setting: MDR Gram neg, MRSA, VRE
• Examples of community : MRSA, PRSP, Pcn R Quin R N. gonorrhea, antibiotic resistant Salmonella and Shigella
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Emergence of Antibiotic-Resistant Bacteria
S aureus
Gram-negative rods
N. gonorrhoeaePenicillin
Ampicillin
H. influenzae
M. catarrhalis
S. pneumoniae
Enterococcus sp.
1950 1960 1970 1980 1990
Quinolones3rd genCephalosporinsCohen; Science 1992;257:1050
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How extensive is the problem ?
Percentage of Laboratory Isolates Resistant to Antibiotics, Texas
05
101520253035
Vancomycin-resistant
EnterococcusSpecies
Penicillin-resistant
Streptococcuspneumoniae
199920002001
Per
cent
age
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Scope of Problem:S. pneumoniae
• Most common cause of bactemia, bacterial pneumonia, meningitis, OM, sinusitis in childhood.
• Highest rates of invasive pneumococcal disease occur among young children, especially those aged <2 years
• US data: the seven most common serotypes isolated from the blood or CSF of children age <6 years account for 80% of disease
• Antimicrobial resistance is detected most frequently among these same serotypes.
• 1998 surveillance data from eight states: these serotypes accounted for 80% of penicillin-nonsusceptibleisolates.
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Percentage of Invasive Pneumococcal Isolates Nonsusceptible to Penicillin, Selected States,1997
Perc
e nta
ge
0
5
10
15
20
25
30
35
40
MD CA OR CT MN GA TN
Resistant
Intermediatesusceptibility
557 182178 603
435
843439
CDC, MMWR 1999; 48(30):656-661
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Mechanisms of Bacterial Resistance : how DO they do it ??
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Antibiotic Pressure and Resistance in BacteriaHow does it occur?
• All antibiotics do NOT kill bacteria in the same way.
• Various classes of antibiotics work on different aspects of bacterial replication.
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Folic acid synthesis
ß-lactams & Glycopeptides (Vancomycin)
50 50 5030 30 30
DNA
mRNA
Ribosomes
PABA
DHFA
THFA
Cell wall synthesis
DNA gyraseQuinolones
Protein synthesis inhibition
Protein synthesis inhibitionTetracyclines
Protein synthesis mistranslation
Macrolides & Lincomycins
DNA-directed RNA polymerase
Rifampin
Sulfonamides
Trimethoprim
Aminoglycosides
Cohen. Science 1992; 257:1064
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Antibiotic Pressure and Resistance in BacteriaHow does it happen ?
• Bacteria can become resistant as a result of genetic mutations; these can be transferred between bacteria and groups of bacteria.
• Under selective pressure of antibiotic exposure, these strains then proliferate.
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Antibiotic Pressure and Resistance in BacteriaWhat happened to S. aureus ?
• Can become Resistant to the B-lactam drugs (PCNs, Cephalosporins) by making a B-lactamase.
• In response to development of a drug that is stable to this mechanism (methicillin/oxacillin), S. aureus alters its binding site (PBP): MethicillinResistant S. aureus (MRSA)
• In response to use of other types of antibx to combat MRSA: few strains now with decr. sensto vancomycin, clindamycin.
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Antibiotic Pressure and Resistance in BacteriaWhat happened to S. aureus ?
• Reports of increasing use of third gencephalosporins and quinolones related to emergence of MRSA.
• Some data suggest that quinolones enhance expression of methicillin reistance in SA in vitro
• Outbreaks of MRSA have been reduced by curbing antibiotic use: esp cephalosporins
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Antibiotic Pressure and Resistance in BacteriaWhat factors promote their development and spread ?
Alteration of normal flora
Practices contributing to misuse of antibiotics
Settings that foster drug resistance
Failure to follow infection control principles
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Practices Contributing to Misuse of Antibiotics
Inappropriate specimen selection and
collection
Inappropriate clinical tests
Failure to use stains/smears
Failure to use cultures and susceptibility
tests
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Practices Contributing to Misuse of Antibiotics
Inappropriate specimen selection and
collection
Inappropriate clinical tests
Failure to use stains/smears
Failure to use cultures and susceptibility
tests
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Inappropriate Antibiotic Use
Use of antibiotics with no clinical indication (eg, for viral infections)
Use of broad spectrum antibiotics when not indicatedInappropriate choice of empiric antibiotics
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Inappropriate Drug Regimen
Inappropriate dose - ineffective concentration of antibiotics at site of infection
Inappropriate route - ineffective concentration of antibiotics at site of infection
Inappropriate duration
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Settings that Foster Drug Resistance
Day-care centers
Long term care facilities
Homeless shelters
Jails
Community
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Settings that Foster Drug Resistance
HospitalIntensive care units
Oncology units
Dialysis units
Rehab units
Transplant units
Burn units
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Physicians Can Impact
Patients Other clinicians
Optimize patient evaluation Adopt judicious antibioticprescribing practicesImmunize patients
Optimize consultations with other cliniciansUse infection control measuresEducate others about judicious use of antibiotics
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Controlling Pneumococcal Resistance-Iceland
Public campaign, physician education, and increased antibiotic cost
25
89 90 91 92 93 94 95 960
5
10
15
20
% n
onsu
scep
tible
S. p
neum
onia
e
Stephenson, JAMA 1996;275:175
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Controlling Erythromycin Resistance in Group A Streptococci - Finland
YearEry
thro
myc
inco
nsum
ptio
n (D
DD
/100
0 )E
rythromycin resistance (%
)
87 88 89 90 91 92 93 94 95 960
1
2
3
4
5
10
15
20
25
30
Erythromycin resistance
Erythromycin consumption
Seppala, NEJM 1997;337:441
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Antibiotic Pressure and Resistance in Bacteria:Conclusions
• Bacteria evolve resistance to antibiotics in response to environmental pressure exerted by the use of antibiotics.
• Many of these bacteria are significant pathogens.
• Our responsibility to our community is to use antibiotics prudently, for appropriate indications.