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

Uso racional de antibióticos en

infecciones comunes

François BoucherMD, FRCPC

The complete PowerPoint file of this presentation is available at the following URL:

http://tinyurl.com/6wxp7ca

francois@boucher.cc

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"

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

William Osler, MD (1849 - 1919)

Key facts oninappropriate use of antibiotics

Inappropriate use of antibioticsis 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 ofantibiotics in children

Considerations before prescribing

1. Is an antibiotic necessary? 2. What is the most appropriate antibiotic? 3. What dose, frequency, route and duration? 4. 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 CA-MRSA 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 CephIConsider Clinda, IVIG

Necrotizing pneumonia

Vanco

Sepsis syndrome, endocarditis

Vanco ± Clox or CephIConsider 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;e1034www.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.htmPediatrics 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 efficacypreventing 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

Dru

g C

on

cen

tra

tio

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Time

Peak (Peak/MIC)

Area Under the Curve (AUC/MIC)

Time above MIC

MIC

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

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;128:595–610www.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 BoucherMD, FRCPC