OVERVIEW

Antibiotic Use Leads to

Antibiotic Resistance

Inpatient

Agriculture

Outpatient

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Outbreaks of Escherichia coli O157 in spinach and
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Emerging and re-emerging
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penicillin 3
penicillin (ampicillin)
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Antibiotic Mechanism of Action

Linezolid

Daptomycin
Daptomycin
Linezolid
Daptomycin





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 Mechanisms Of Antibiotic Resistance


Decreased

Permeability

Alteration in
Target
Molecule
Cycle of Antibiotic
R

Resistance Acquisition:
Bacterial Selection Selection by Drug X
Under increasing
antibiotic selection
pressure:
1. Bacteria resistant to a Replication
particular drug are
selected and replicate
2. Different antibiotics
select different Selection by Drug Y
bacteria but can
select resistant
phenotypes to other
drugs as well Replication
3. This results in
multidrug-resistant
(MDR) organisms and
increases their total
Resistance to: Drug Z
number Drug X Drug Y


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Microbiome and normal flora
 Reasons for Antibiotic Overuse :
Conclusions from 8 Focus Groups
Patient Concerns Physician Concerns
Want clear explanation Patient expects
Green nasal discharge antibiotic
Need to return to work Diagnostic uncertainty
Time pressure

Antibiotic Prescription

Barden L.S. Clin Pediatr 1998;37:665


MIC = Minimal inhibitory concentration. Lowest
concentration of antimicrobial that inhibits growth of
bacteria. Commonly used in clinical lab

MBC = Minimal bactericidal concentration.

Concentration of an antimicrobial that kills bacteria.
Used clinically only in special circumstances

Breakpoint = The MIC that is used to designate

between susceptible and resistant. Arbitrarily set by a
committee
Minimum Inhibitory
Concentration

MIC = 6.25 mcg/mL

 Automated Methods

Well Plate for MIC Testing

Many Labs Use

Automated Testing
 Other Methods for Determining
Susceptibility

E-test
Kirby-Bauer
Disk Diffusion

Agar dilution
 Concept of Breakpoint to Determine
EXAMPLE: Susceptibility
Susceptibility
Antibiotic MIC Breakpoint Susceptibility
testing for a
single isolate of Ampicillin >16 8 Resistant
Pseudomonas Gentamicin 2 4 Susceptible
aeruginosa
Cephalothin >16 N/A Resistant
Cefepime 8 32 Susceptible
Cefotaxime 16 16/32 Intermediate
-Breakpoint for Ceftazidime 2 32 Susceptible
intermediate resistance
for meropenem is 4 and Aztreonam 4 16 Susceptible
for
Ciprofloxacin 2 2 Resistant
piperacillin/tazobactam
(pip/tazo) 32 Amp/Sulbactam >16 8 Resistant
-Pip/tazo is the better Meropenem 4 4/8 Intermediate
choice between the two
-Ciprofloxacin is a poor
Pip/tazo 8 32-64/128 Susceptible
choice even though the
MIC is lowest of the three
 Increase in MRSA Prevalence in US
Comparison to Other Drug-Resistant Organisms

Wenzel et. al. ICHE 2008;29;1012

 Surgical Site Infections
Impact of Resistance on Clinical Outcomes

MSSA MRSA
Unadjusted (N=165) (N=121) P Value

Mortality, 90-day 6.7% 20.7% P<.001

Length of stay:
median days
After surgery 14 (7-25) 23 (12-38) P<.001
After infection 10 (4-17) 15 (7-30) P=.001

Adjusted* mortality for MRSA (P=0.003)

*Adjusted for other predictors of mortality: age, physical status, duration of surgery.
Engemann JJ, et al. Clin Infect Dis. 2003;36:592-598.
 Decreased Susceptibility of S. pneumoniae to
Fluoroquinolones (FQRSP) in Canada
Relationship of Resistance to Antibiotic Use
5 15 - 64 y.o
6
Susceptibility to Fluoroquinolones (%)

4.5 > 64 y.o

# of Prescriptions / 100 Persons

4 # of Rx/100 persons 5
S. pneumo. with Reduced

3.5 4
3
2.5 3
2
1.5 2
1 1
0.5
0 0
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

Chen et. al., NEJM 1999;341:233-9

 Community-Acquired Resistant
E. Coli
Mostly UTIs
Young healthy women in
addition to the elderly
10-20% now resistant to
fluoroquinolones
30-50% resistant to
trimethoprim-
sulfamethoxazole
CTX-M -lactamases
becoming more common
Cause cephalosporin resistance

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