Antimicrobial therapy

and Antibiotic policy

Dr Siti Zulaikha Zakariah
MD Year 2 Semester 1
 Overview on
antimicrobial therapy
Learning in systemic infections
objectives Rational use of
antimicrobial agents
 minimize morbidity and
mortality due to
antimicrobial-resistant
Aims of infection
antimicrobial
policy preserve effectiveness of
antimicrobial agents in the
treatment and prevention of
communicable diseases.
General principles
Empiric vs Interpretation of
Obtaining an Timing of Initiation
Definitive Antimicrobial
Accurate Infectious of Antimicrobial
Antimicrobial Susceptibility
Disease Diagnosis Therapy
Therapy Testing Results

Bactericidal vs Use of
Oral vs intravenous
Bacteriostatic Antimicrobial Host factors
therapy
Therapy Combinations

Pharmacodynamic Efficacy at the site Use of therapeutic

characteristics of infection drug monitoring
Accurate Infectious Disease Diagnosis

Determine Define Establish

Site of infection Host (eg. Microbiological

immunocompromised, diagnosis
diabetic, of advanced
age)
 guided by urgency of the situation

In critically ill patients, empiric therapy should be

Timing of initiated immediately after/ concurrently with
collection of diagnostic specimens
Initiation of
Antimicrobial In more stable patients, antimicrobial therapy should
be withheld until appropriate specimens have been
Therapy collected and submitted to the microbiology laboratory

Premature initiation of antimicrobial therapy suppress

bacterial growth à unable to establish a
microbiological diagnosis,
Empiric vs Definitive Antimicrobial Therapy

• microbiological results are not available for 24 to 72 hours, initial therapy for
infection is often empiric and guided by the clinical presentation.
• Selection criteria:
• site of infection and the organisms most likely to be colonizing that site
• prior knowledge of bacteria known to colonize a given patient
• local bacterial resistance patterns or antibiograms that are available for
important pathogens at most hospitals.
• Broad spectrum antibiotics given initially
• Deescalate once susceptibility results available
Interpretation of Antimicrobial
Susceptibility Testing Results
• Minimum inhibitory concentration
Bactericidal vs Bacteriostatic Therapy

Bactericidal drugs cause death and disruption of the bacterial cell,

include drugs that primarily act on the cell wall (eg, beta-lactams), cell
membrane (eg, daptomycin), or bacterial DNA (eg, fluoroquinolones).
Bacteriostatic agents inhibit bacterial replication without killing the
organism

Bactericidal agents are preferred in the case of serious infections eg.

endocarditis and meningitis.
 Antimicrobial Combinations

1 2 3
Exhibit Synergistic Activity Extend the Antimicrobial Prevent Emergence of
Against a Microorganism Spectrum for Treatment of Resistance
• eg, treatment of endocarditis Polymicrobial Infections • Eg. HIV, TB
caused by Enterococcus species
with a combination of penicillin
and gentamicin
Host factors

Renal and
Genetic
hepatic Age
variation
function

History of
Pregnancy and History of
recent
Breastfeeding allergy
antibiotic use
 Severity of infections e.g. UTI, CAP

Oral vs
normal gastrointestinal function
intravenous
therapy
patients initially treated with parenteral
therapy can be switched to oral antibiotics
when they become clinically stable
 • Time dependent vs concentration
dependent
• Time-dependent activity (e.g. beta-
lactams and vancomycin) have
relatively slow bactericidal action
Pharmacodynamic • Concentration-dependent killing
Characteristics (aminoglycosides,
fluoroquinolones, metronidazole,
and daptomycin) have enhanced
bactericidal activity as the serum
concentration is increased.
 • Antimicrobial concentrations at some

Efficacy sites (eg, ocular fluid, CSF, abscess cavity,

prostate, and bone) are often much
lower than serum levels

at the • Examples:
• Fluoroquinolones achieve high

site of
concentrations in the prostate
• 1st and 2nd-generation
cephalosporins and macrolides do

infection
not cross the blood-brain barrier
 Use of therapeutic drug monitoring

Toxicity at high Therapeutic failure

Narrow
levels at low drug levels
therapeutic index
(aminoglycosides) (vancomycin)
Questions to ask
1.

• Is an antibiotic indicated on the bases of

clinical findings?
2.

• Have appropriate clinical

specimen been obtained,
examined and cultured?
3.

• What pathogens are most likely

to be causing the infection?
 4.

• If multiple antibiotics are available to treat this likely or

known organism, which agent is best for a given patient?
(This question involves such factors as drug of choice,
pharmacokinetics of agents, toxicology, cost and
bactericidal compared with bacteriostatic agents.)
 5.

• Is an antibiotic combination
appropriate?
6.

• Are there special considerations related specifically to given patient?

• Renal function?
• Liver function?
• Allergies?
• Pregnancy?
• ……?
7.

• What is the best route of

administration?
 • What is the appropriate dose?
8.
• (Renal dosing)
9. • Will initial therapy require modification after
culture data are returned?
10.

• What is the optimal duration of

treatment?
 • First choice agents:
• Nitrofurantoin (100 mg twice daily for 5–7
days)
• Cephalexin 5-7 days
Empirical treatment • Alternative agents:
• Fluoroquinolones (dose varies by agent; 3–day
of acute regimen)

uncomplicated • Trimethoprim-sulfamethoxazole (160/800 mg

twice daily for 3 days)
cystitis • Beta-lactams (dose varies by agent; 3–5 day
regimen
Community acquired pneumonia

• Streptococcus pneumoniae, Mycoplasma pneumoniae,

Haemophilus influenzae, Chlamydia pneumoniae, viruses,
Legionella
• blood and sputum cultures, serology to Mycoplasma and Chlamydia
• Previously healthy and no risk factors for drug-resistant
• Macrolide
• Beta-lactam or doxycycline
Bacterial (tonsilo)pharyngitis

• Group A beta-hemolytic streptococcus

• Drug of choice penicillin (V p.o., G i.v.)
• Macrolides are alternative drugs for patients who are allergic to penicillin
• 10-day course
Thank you