Transcript Rational antibiotic choices

Uso racional de
antibióticos en
infecciones comunes
François Boucher
MD, FRCPC
The complete PowerPoint file of this presentation is
available at the following URL:
http://tinyurl.com/6wxp7ca
[email protected]
Why take antibiotics?
• "The desire to take
medicine is perhaps the
greatest feature which
distinguishes man from
animals."
• "One of the first duties of
the physician is to
educate the masses not
to take medicine"
William Osler, MD (1849 - 1919)
H. Cushing, Life of Sir William Osler (1925)
Key facts on
inappropriate use of antibiotics
Inappropriate use of antibiotics
is a worldwide problem
• More than 50% of all medicines are prescribed,
dispensed or sold inappropriately, and half of all
patients fail to take medicines correctly.
• The overuse, underuse or misuse of medicines
harms people and wastes resources.
• More than 50% of all countries do not implement
basic policies to promote rational use of medicines.
• In developing countries, less than 40% of patients
in the public sector and 30% in the private sector
are treated according to clinical guidelines.
Consequences of inappropriate
antibiotic use
• Antimicrobial resistance.
• Adverse drug reactions and medication errors.
• Lost resources.
• Eroded patient confidence.
Appropriate use of
antibiotics in children
Considerations before prescribing
1.
2.
3.
4.
Is an antibiotic necessary?
What is the most appropriate antibiotic?
What dose, frequency, route and duration?
How to improvethe chances that the tretament
will be effective?
Is an antibiotic necessary?
• Useful only for the treatment of bacterial infections
• Not all fevers are due to infection
• Not all infections are due to bacteria
• There is no evidence that antibiotics will prevent
secondary bacterial infection in patients with viral
infection
• The treatment of certain infections might be better
achieved with other means, such as surgery:
• Debridement of local cellulitis in moderate CAMRSA infections of the skin
Recommended therapy for CA-MRSA
Infection
Severity
Choice of antibiotic
Skin/soft tissue
Mild
Topical, drainage
Moderate
Clinda, T/S, Doxycyclin
Severe
Vanco ± Clox or CephI
Osteomyelitis
Vanco, Clinda, T/S ± Rif
Pyomyositis,
necrotizing fasciitis
Vanco ± Clox or CephI
Consider Clinda, IVIG
Necrotizing
pneumonia
Vanco
Sepsis syndrome,
endocarditis
Vanco ± Clox or CephI
Consider Clinda, IVIG
Barton M et al.
Can J Infect Dis Med Microbiol 2006; 17(Suppl C): 1B-24B
Choice of antimicrobial agent
Based on three main factors:
• Etiological agent
• Patient-related factors
• Antibiotic-related factors
Antibiotic choice:
Etiological agent
• Be careful of the identification of the agent by the
laboratory
• Example: UTI
• How was sample collected?
• Contamination of sample is frequent, even in
the best conditions
• Consider the symptoms…
• Consider the urinalysis…
Antibiotic choice:
Etiological agent
• Most probable agents: based on epidemiology and
clinical experience
• Importance of local antibiotic resistance data
• Resistance patterns vary
• From country to country
• From hospital to hospital in the same country
• From unit to unit in the same hospital
• With time
• Regional/country data useful only for following
trends, NOT guide empirical therapy
Examples of local sensitivity issues
• S. aureus in Quebec City
• Universally sensitive to clindamycin until around
2006
• IV Clindamycin was a good choice in pediatrics
for treatment of skin and other conditions
• Active against S. aureus and Group A strep
• Not as hard on patients’ veins as cloxacillin
• Great tissue penetration
• Local activity not inhibited by local conditions
• Since 2006: 25% strains show resistance to
clindamycin
• Treatment failures observed
Examples of local sensitivity issues
• E. coli
• Resistance to ampicillin has increased rapidly in
the past ten years
• ? consequence of GBS prevention in
parturieny women?
• Now 85% strains are resistant to ampicillin
• Issues with treatment of acute pyelonephritis in
children <1 year old
• Alternatives: oral Cefixime, Ciprofloxacin…
Pediatrics 2011:128(3):595
www.pediatrics.org/cgi/doi/10.1542/peds.2011-1330
Ciprofloxacin in children?
• Original quinolone: Nalidixic acid
• Inhibitors of DNA gyrase
• Toxicity on the cartilage of immature animals
(standard preclinical model)
• Never evaluated in clinical studies in infants &
children
• Ciprofloxacin : Only oral agent active against P.
aeruginosa. Pneumococcus is resistant
• End 1990s: clinical studies in children at the NIH
NCI, and in Sweden
Pediatrics 2011;128;e1034
www.pediatrics.org/cgi/doi/10.1542/peds.2011-1496
Ciprofloxacin in children?
• Ciprofloxacin is safe in children
• Approved by FDA in December 2003
• Its use may be considered
• In infections caused by P. aeruginosa or other
multiply-resistant Gram-negative organisms
• When venous access is impossible
• Dosage :
• PO : 30 mg/kg/d ÷ BID
• IV : 10-60 mg/kg/d ÷ q 12 h
• Norfloxacin & ofloxacin tablets
http://www.fda.gov/cder/pediatric/labelchange.htm
Pediatrics 2011;128;e1034
www.pediatrics.org/cgi/doi/10.1542/peds.2011-1496
Antibiotic choice:
Patient-related factors
• Age
• Physiological factors
• Comorbidoties
• Genetic factors
• Pregnancy
• Site and severity of infection
• Allergies
Antibiotic choice:
Antibiotic-related factors
• Pharmacokinetic/pharmacodynamic (PK/PD) profile
• Absorption
• Excretion
• tissue levels, peak levels, AUC,
• Time above MIC
• Toxicity and other adverse effects
• Drug-drug interactions
• Cost
PK/PD factors
 Increasing knowledge on the association between
PK/PD parameters on
 clinical efficacy
 preventing emergence of resistance
 Enables optimization of dosage regimens
 In some instances this has led to a redefinition of
interpretative breakpoints in sensitivity testing
Antimicrobial activity
Drug Concentration
Peak (Peak/MIC)
Area Under the Curve (AUC/MIC)
MIC
Time above
MIC
Time
Pharmacodynamic properties of
antibiotics
Type of bactericidal
profile
Dose-dependent
Aminoglycosides,
quinolones
Time-dependent
Penicillin, cephalosporins
Cumulative-dose
dependent
Clarithromycin,
clindamycin
Important
parameter
Dosage optimization
Cmax / MIC
Prolonged PAE
Single daily dose
T > MIC No PAE
Multiple DD or
continuous infusion
AUC / MIC
Prolonged PAE
Total dose and
duration
PAE: Post-Antibiotic Activity
Antibiotic-related factors: Synergy
• Synergy against Gram-negatives
• Treating CF chest exacerbations with
combinations of antibiotics
• Ticarcillin-clavulanate and tobramycin
• Neutropenic patients with Gram-negative
infections
• Severe invasive Group-A streptococcal infections
• Penicillin and clindamycin
Hand infections
• Always severe
• Need close monitoring
and IV antibiotics
• Etiology:
• S. aureus and
Group-A
streptococcus
• P. multocida
• Eikenella corrodens
Treatment of invasive cellulitis
• Penicillin 250,000 U/kg/day ÷ q4-6hr AND
• Clindamycin 40 mg/kg/day ÷ q8hr
• Why a bacteriostatic antibotic with a bactericidal
one? Is this not contraindicated?
The "Eagle" effect
Antibiotic choice:
Antibiotic-related factors: Cost
• Not just the unit cost of the antibiotic
• Materials for administration of drug
• Labour costs
• Expected duration of stay in hospital
• Cost of monitoring drug levels
• Expected compliance
Choice of regimen
• Oral vs parenteral
• Traditional view
• « serious = parenteral »
• Previous lack of broad spectrum oral
antibiotics with reliable bioavailability
• Improved oral agents
• Higher and more persistent serum and tissue
levels
• For certain infections as good as parenteral
Treatment of febrile UTIs in children
• In the past: hospital-based IV therapy
• Usually Ampicillin + gentamicin
• From 1995: Amoxicillin and once-daily IM
gentamicin, then oral therapy after 2-3 days
• Today: Cefixime PO 8 mg/kg q12h x 2 then q24h
• Uncomplicated UTIs
• Child aged 6 months or more
• Non-toxic, well hydrated
• Good compliance/follow-up
• No comorbidity, allergies etc.
Pediatrics 2011;128:595–610
www.pediatrics.org/cgi/doi/10.1542/peds.2011-1330
Treatment of uncomplicated
osteomyelitis/septic arthritis
• Initial IV therapy for 7-10 days in-hospital
• Followed by either
• Home IV antibiotic therapy for 3-4 weeks
• Oral antibiotic: Cephalexin 100 mg/kg/day ÷
q8h for 3-4 weeks
• Specific conditions apply
• With weekly supervision and 24/7 availability in
case of problems
Clinical Infectious Diseases 2009; 48:1201–10
Pediatr Infect Dis J 2010;29: 1123–11
Advantages of oral treatment
• Eliminates risks of complications associated with
intravascular lines
• Shorter duration of hospital stay
• Savings in nursing time
• Savings in overall costs
• Greater patient satisfaction
In conclusion
• It is an essential role of the pediatrician to ensure
that antibiotics are used appropriately
• This is easy! Ask simple questions before initiating
any antimicrobial treatment.
• Be systematic in your approach
• Consider alternatives
• Know the important facts about
• Best schedules and duration for specific
infections
• New ways of using old antibiotics
• Availability of new agents and new treatment
modalities
Thank you
François Boucher
MD, FRCPC