1. Uso racional de antibióticos en infecciones comunes
François Boucher
MD, FRCPC

2. http://tinyurl.com/6wxp7ca francois@boucher.cc
The complete PowerPoint file of this presentation is available at the following URL:

3. 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 ( )
H. Cushing, Life of Sir William Osler (1925)

5. Key facts on inappropriate use of antibiotics

6. 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.

7. Inappropriate use of antibiotics is a worldwide problem
A combination of health-care provider education and supervision, consumer education, and an adequate medicines supply is effective in improving the use of medicines, while any of these interventions alone has limited impact.

8. Common problems include
Polypharmacy (use of too many medicines);
Overuse of antibiotics and injections;
Failure to prescribe in accordance with clinical guidelines;
Inappropriate self-medication.

9. Consequences of inappropriate antibiotic use
Antimicrobial resistance.
Adverse drug reactions and medication errors.
Lost resources.
Eroded patient confidence.

10. Appropriate use of antibiotics in children

11. Considerations before prescribing
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?

12. 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 CA-MRSA infections of the skin

13. 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
Consider Clinda, IVIG
Necrotizing pneumonia
Vanco
Sepsis syndrome, endocarditis
Barton M et al.
Can J Infect Dis Med Microbiol 2006; 17(Suppl C): 1B-24B

14. Choice of antimicrobial agent
Based on three main factors:
Etiological agent
Patient-related factors
Antibiotic-related factors

15. 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…

16. 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

17. 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

18. 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

19. 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

20. 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 : mg/kg/d ÷ q 12 h
Norfloxacin & ofloxacin tablets
Pediatrics 2011;128;e1034

21. Antibiotic choice: Patient-related factors
Age
Physiological factors
Comorbidoties
Genetic factors
Pregnancy
Site and severity of infection
Allergies

22. 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

23. 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

24. Antimicrobial activity
Drug Concentration
Time
Peak (Peak/MIC)
Area Under the Curve (AUC/MIC)
Time above MIC
MIC

25. Pharmacodynamic properties of antibiotics
Type of bactericidal profile
Important parameter
Dosage optimization
Dose-dependent Aminoglycosides, quinolones
Cmax / MIC Prolonged PAE
Single daily dose
Time-dependent Penicillin, cephalosporins
T > MIC No PAE
Multiple DD or continuous infusion
Cumulative-dose dependent Clarithromycin, clindamycin
AUC / MIC Prolonged PAE
Total dose and duration
PAE: Post-Antibiotic Activity

26. 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

27. Hand infections Always severe Need close monitoring and IV antibiotics
Etiology:
S. aureus and Group-A streptococcus
P. multocida
Eikenella corrodens
All infections involving the hand should be taken very seriously and be treated with intravenous antibiotics and drained by a hand surgeon if suppurative. The nature of the injury that led to the infection should also be taken into account; for example, if it is a closed fist injury (figure 6), one may expect more mouth anaerobes, possibly Eikenella corrodens, to be contributing to the infection. In this case, adding Pfizer’s Unasyn (the drug of choice for Eikenella) to the clindamycin would be appropriate. Unlike most other anaerobes, Eikenella does not respond to clindamycin. If the infection results from a dog or cat bite (figure 7), then Pasteurella multocida should be considered, which is also covered by Unasyn. In fact, Unasyn would be all that’s normally needed for hand infections in the days prior to MRSA ruling the world of S. aureus.
The speed at which the infection progresses may also lend a clue. Hand infections that seem to be getting worse by the hour are more likely to be due to group A streptococcus (GAS), as shown in figures 8–10, which show a 10-year-old whose right index finger was cut by a knife the day before. He presented with a fever of 103.5° F and a 12-hour history of painful swelling of his right hand. The pictures were taken approximately 36 hours after the injury. He had surgical drainage of his hand later that day, and the culture grew group A streptococcus. Pasteurella shares a similar tendency to develop rapidly, whereas Staph infections tend to be slower to develop and progress.

28. 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?

29. The "Eagle" effect

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. François Boucher MD, FRCPC
Thank you
François Boucher
MD, FRCPC