Transcript Questions to ask when choosing antibiotics?

General Principles of
Antimicrobial Therapy
Concept #1: The guiding
principle of antibiotic selection
Antibiotic coverage should be kept to
the
narrowest spectrum,
least expensive,
least toxic agent(s)
that will adequately treat the most
likely pathogens.
Concept # 2: It is safe to be
focused
When a causative infectious
agent has been identified,
antibiotic coverage should be
narrowed to treat that
organism.
Concept #3: Reasons to use two or
more antibiotics simultaneously
• When one antibiotic cannot adequately cover the
•
•
•
•
•
empiric spectrum
When synergy is necessary to obtain cidal levels
(e.g., serious enterococcal and pseudomonal
infections)
To prevent the emergence of resistance (e.g., TB,
HIV)
To achieve additive effects on resistant infections
(e.g., PVE, H. pylori)
To treat multiple phases (forms) of the same
pathogen (e.g., TB, parasitic diseases)
When a single antibiotic would have to be given in
toxic doses
Using antibiotics to inhibit toxin
production
• Usually this is done for severe toxigenic staph or
•
strep infection (e.g., TSS, necrotizing fasciitis)
The theory is that, in infected areas where microbial
density is high, the bacteria
– are nutrient-limited and in stationary phase
– do not synthesize PBPs
– are less susceptible to beta-lactam antibiotics, BUT
– are alive and actively synthesizing toxins
•
•
Hence, treatment with protein synthesis inhibitor (to
inhibit toxin production) should improve outcome.
Although clindamycin is commonly added to betalactams in severe Gram-positive infection, there is
little clinical data to support this practice (see
aminal model results on next slide).
Efficacy of clindamycin in an animal
model of streptococcal myositis
(from Stevens et al. JID 1988; 158: 23)
100
90
80
%
survival
after
14 d
70
Clindamycin
60
50
40
30
Erythromycin
Untreated @ 16h
Penicillin G
20
10
0
2
4
6
8
10
12
14
16
Delay in treatment (hrs)
18
Reasons NOT to use multiple
antibiotics when you don’t have to
• May result in antagonism between agents
•
(depending on the combination)
Increases the likelihood of a toxic or allergic
reaction to one of the agents
– Additive (I.e., different adverse effects from different
–
•
•
agents)
Synergistic (e.g., increased nephrotoxicity with
vancomycin and gentamicin)
Encourages the development of multi-drug
resistance
Increases the cost of care
Concept # 4 :“More of a good
thing is NOT always better”
• The dosing of antibiotics should be adjusted
•
to provide effective levels at the site of
infection.
Unnecessarily high doses of some antibiotics
may -– increase the risk of toxicity
– paradoxically result in less killing in
vitro (the “Eagle effect”). The significance
of this effect in vivo is not known.
Killing of enterococci by
amoxicillin over 24 hrs at
concentrations of 1, 10, and 100
mcg/ml (compared with no
antibiotic, i.e., control)
(from Antimicrob Ag Chem 1986;30:258)
Concept # 5: “Not all fevers are infection.”
Common non-infectious causes of fever:
•Drugs
•Immunologically-based disorders
–Temporal arteritis
–Still’s disease
–Vasculitis
–Lupus
•Inflammatory and granulomatous conditions
–Inflammatory bowel disease
–Wegener’s granulomatosis
–Sarcoidosis
–Graft-versus-host disease
•Neoplasms
•Endocrine disorder
–Thyroid disease
–Hypoadrenalism
•Other
–Thrombophlebitis and pulmonary embolism
–Liver disease/cirrhosis
–CNS disorders
Concept # 6: Antibiotics should be dosed
according to their pharmacokinetics and
pharmacodynamics
Advantages of single daily
dosing of aminoglycosides
For
example . . .
• Equivalent bacteriologic cure and outcome
• Effective because
–Post-antibiotic effect
–Concentration dependant killing
• Decreased toxicity
• Avoids overuse of alternative agents
Principles of Antimicrobial Use
(summary)
• Use narrowest spectrum, least expensive,
•
•
•
least toxic antibiotic to cover likely
organisms
Direct therapy based on culture and
susceptibility data
Avoid overlapping antimicrobials
Combination therapy for resistant Gram
negative organisms, nosocomial pneumonia
and febrile neutropenia
Resources
1. Antimicrobial guidelines
- Booklet
https://ummcpharmweb.med.umich.edu/di/clinical/abxbook/ant
imicrobial_guidelines/
2. Antimicrobial Restriction Program
3. Infectious Diseases Consult Service