Transcript Le papillomavirus humain et le vaccin contre le PVH en 2006

Community acquired pneumonia (CAP):
Why is this still a problem?
François Boucher
MD, FRCPC
Objectives
After this presentation, participants will be able to:
• Determine appropriate agents, routes and duration
of treatment.
• Recognize how local epidemiology influences
treatment choices.
• Manage complications of CAP.
Emergent problems in pediatric
community-acquired pneumonia
• Severe pneumonia
• Pulmonary abscess formation: GAS
• Pulmonary necrosis & fibrosis: MRSA
• Pneumatocoeles: S. aureus
• Resistant organisms: S. pneumoniae 19A
• Parapneumonic effusion
• Increasing incidence
• Difficult management
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Incidence in Canadian children
• 41,000 children <5 years of age treated in the
community each year
• 9600 hospitalized
• older children have decreased incidence
• leading cause of mortality and morbidity amongst
Canadian Inuit; 1999-2000- outbreak in several
communities on Baffin Island (adult and child)
Pathogens
• CAP generally caused by a single organism
• Even with extensive diagnostic testing, most
investigators cannot identify a specific etiology for
CAP in ≥ 50% of patients.
• In those identified, S. pneumoniae is causative
pathogen 60-70% of the time
Pathogens in pediatric CAP
Pediatr Infect Dis J 2002 21: 592-598
Pneumococcal pneumonia
• Most common cause of CAP
• Gram positive diplococci
• “Typical” symptoms (e.g. malaise, shaking chills,
fever, pleuritic hest pain, cough)
• Lobar infiltrate on CXR
• Rarely bacteremic in children
Atypical Pneumonia
• Second most frequent cause (especially in younger
population)
• Commonly associated with milder symptoms:
subacute onset, non-productive cough, no focal
infiltrate on CXR
• Mycoplasma: younger Pts, extra-pulmonary
symptoms (URI, rash), headache, sore throat
• Chlamydia pneumoniae: young adults, year round,
URI, sore throat
Viral Pneumonia
• Most common cause in children
• RSV, influenza, parainfluenza
• Influenza is the most important viral cause in
adults, especially during winter months
• Post-influenza pneumonia (secondary bacterial
infection)
• S. pneumo, Staph aureus
Other bacteria
• Staphylococcus aureus
• Severe disease, prior viral pneumonia
• Gram negative bacteria
• Klebsiella – neonates
• Branhamella catarrhalis - sinus disease, otitis,
COPD
• H. influenzae - Rare
• Anaerobes
• Aspiration pneumonia, dental disease
Clinical Features of C. Trachomatis
Pneumonia
• Onset at 3 to 11 wks of age
• Cough greater than one week in duration
• Prior conjunctivitis
• Afebrile tachypnea with diffuse rales
• Hyperinflation and interstitial infiltrates on chest
film
• Eosinophilia
• Increased IgM
• Increased IgA and IgG
Management of CAP:
When to obtain a CXR
• Child < 5 years of age with high fever and high
WBC of uncertain source
• Ambigusous clinical findings
• Suspected complication, i.e. pleural effusion
• Pneumonia is prolonged and unresponsive to
treatment
Management of CAP:
Considerations for admission
• Child aged less than 6 months of age
• Toxic appearance
• Severe respiratory difficulty
• TcSaO2 < 95%
• Dehydration, vomiting
• No response to oral medication
• Immunocompromised child
• Social circumstances / poor compliance
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Child < 5 years old
• Presumed bacterial pneumonia
• Amoxicillin, oral (90 mg/kg/day in 2 doses)
Alternative: oral amoxicillin clavulanate
(amoxicillin component, 90 mg/kg/day in 2
doses)
• Presumed atypical pneumonia
• Azithromycin oral (10 mg/kg on day 1,
followed by 5 mg/kg/day once daily on days 2–
5);
• Alternatives: oral clarithromycin (15
mg/kg/day in 2 doses for 7-14 days) or oral
erythromycin (40 mg/kg/day in 4 doses)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Child ≥ 5 years old
• Presumed bacterial pneumonia
• Oral amoxicillin (90 mg/kg/day in 2 doses to a
maximum of 4 g/day); for children with
presumed bacterial CAP who do not have
clinical, laboratory, or radiographic evidence
that distinguishes bacterial CAP from atypical
CAP, a macrolide can be added to a b-lactam
antibiotic for empiric therapy;
• alternative: oral amoxicillin clavulanate
(amoxicillin component, 90 mg/kg/day in 2
doses to a maximum dose of 4000 mg/day, eg,
one 2000-mg tablet twice daily)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Child ≥ 5 years old
• Presumed atypical pneumonia
• Oral azithromycin (10 mg/kg on day 1,
followed by 5 mg/kg/day once daily on days 2–
5 to a maximum of 500 mg on day 1, followed
by 250 mg on days 2–5); alternatives: oral
clarithromycin (15 mg/kg/day in 2 doses to a
maximum of 1 g/day); erythromycin,
doxycycline for children >7 years old
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Inpatient (All ages)
• Presumed bacterial pneumonia
• Ampicillin or penicillin G;
• alternatives: ceftriaxone or cefotaxime;
• addition of vancomycin or clindamycin for
suspected CA-MRSA
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Inpatient (All ages)
• Presumed atypical pneumonia
• Azithromycin (in addition to ß-lactam, if
diagnosis of atypical pneumonia is in doubt);
• alternatives: clarithromycin or
erythromycin; doxycycline for children >7
years old; levofloxacin for children who have
reached growth maturity, or who cannot
tolerate macrolides
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Not completely immunized
• Presumed bacterial pneumonia:
• Ceftriaxone or cefotaxime; addition of
vancomycin or clindamycin for suspected CAMRSA;
• alternative: levofloxacin; addition of
vancomycin or clindamycin for suspected CAMRSA
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Not completely immunized
• Presumed atypical pneumonia
• Azithromycin (in addition to ß-lactam, if
diagnosis in doubt);
• alternatives: clarithromycin or
erythromycin; doxycycline for children >7
years old; levofloxacin for children who have
reached growth maturity or who cannot tolerate
macrolides
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Mild case or step-down therapy
• Preferred: amoxicillin (90 mg/kg/day in 2 doses
or 45 mg/kg/day in 3 doses);
• Alternatives: second- or third-generation
cephalosporin (cefpodoxime, cefuroxime,
cefprozil); oral levofloxacin, if susceptible (16–
20 mg/kg/day in 2 doses for children 6 months to 5
years old and 8–10 mg/kg/day once daily for
children 5 to 16 years old; maximum daily dose,
750 mg) or oral linezolid (30 mg/kg/day in 3
doses for children <12 years old and 20 mg/kg/day
in 2 doses for children ≥12 years old)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Parenteral therapy
• Preferred: ampicillin (150–200 mg/kg/day every
6 hours) or penicillin (200 000–250 000 U/kg/day
every 4–6 h);
• Alternatives: ceftriaxone (50–100 mg/kg/day
every 12–24 hours) (preferred for parenteral
outpatient therapy) or cefotaxime (150
mg/kg/day every 8 hours);
• may also be effective: clindamycin (40
mg/kg/day every 6–8 hours) or vancomycin (40–
60 mg/kg/day every 6–8 hours)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Highly resistant S.pneumoniae
Parenteral therapy
• Preferred: ceftriaxone (100 mg/kg/day every 12–
24 hours);
• Alternatives: ampicillin (300–400 mg/kg/day
every 6 hours), levofloxacin (16–20 mg/kg/day
every 12 hours for children 6 months to 5 years old
and 8–10 mg/kg/day once daily for children 5–16
years old; maximum daily dose, 750 mg), or
linezolid (30 mg/kg/day every 8 hours for children
<12 years old and 20 mg/kg/day every 12 hours
for children ≥12 years old);
• may also be effective: clindamycin (40
mg/kg/day every 6–8 hours) or vancomycin (40–
60 mg/kg/day every 6–8 hours)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Highly resistant S.pneumoniae
Oral therapy
• Preferred: oral levofloxacin (16–20 mg/kg/day in
2 doses for children 6 months to 5 years and 8–10
mg/kg/day once daily for children 5–16 years,
maximum daily dose, 750 mg), if susceptible, or
oral linezolid (30 mg/kg/day in 3 doses for
children <12 years and 20 mg/kg/day in 2 doses
for children ≥12 years);
• Alternative: oral clindamycin (30–40 mg/kg/day
in 3 doses)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Levofloxacin (Levaquin™)
• Wide-spectrum fluoroquinolone:
• S pneumoniae,
• Haemophilus influenzae (nontypeable),
• Moraxella catarrhalis
• M pneumoniae, C pneumoniae, Legionella
• M. tuberculosis
• Excellent bioavailability: 100% absorbed
• Well tolerated by children
• 5-year safety study reported 11-03-23
• Many interactions
• Medications: anticoagulants
• Natural products
Linezolid (Zyvox™)
• Narrow-spectrum oxazolidinone: Gram+
• S pneumoniae,
• S. aureus, MRSA
• VRE
• Excellent bioavailability: ≈100% absorbed
• Well tolerated for short courses of therapy
• Headache, diarrhea, nausea
• Long-term use: Bone marrow suppression,
thrombocytopenia
• > 2 weeks: neuropathy, lactic acidosis,
mitochondrial toxicity
Management of CAP: Antibiotic therapy
Group A Streptococcus
Parenteral therapy
• Preferred: intravenous penicillin (100 000–250
000 U/kg/day every 4–6 hours) or ampicillin (200
mg/kg/day every 6 hours);
• Alternatives: ceftriaxone (50–100 mg/kg/day
every 12–24 hours) or cefotaxime (150
mg/kg/day every 8 hours);
• may also be effective: clindamycin, if susceptible
(40 mg/kg/day every 6–8 hours) or vancomycin
(40–60 mg/kg/day every 6–8 hours)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Group A Streptococcus
Oral therapy
• Preferred: amoxicillin (50–75 mg/kg/day in 2
doses), or penicillin V (50–75 mg/kg/day in 3 or 4
doses);
• Alternative: oral clindamycin (40 mg/kg/day in 3
doses)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Mycoplasma pneumoniae
Parenteral therapy
• Preferred: intravenous azithromycin (10 mg/kg
on days 1 and 2 of therapy; transition to oral
therapy if possible);
• Alternatives: intravenous erythromycin
lactobionate (20 mg/kg/day every 6 hours) or
levofloxacin (16-20 mg/kg/day every 12 hours;
maximum daily dose, 750 mg)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
Mycoplasma pneumoniae
Oral therapy
• Preferred: azithromycin (10 mg/kg on day 1,
followed by 5 mg/kg/day once daily on days 2–5);
• Alternatives: clarithromycin (15 mg/kg/day in 2
doses) or oral erythromycin (40 mg/kg/day in 4
doses);
• for children >7 years old, doxycycline (2–4
mg/kg/day in 2 doses;
• for adolescents with skeletal maturity,
levofloxacin (500 mg once daily) or
moxifloxacin (400 mg once daily)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Pneumonia caused by MRSA
François Boucher
MD, FRCPC
CA-MRSA: Antibiotic susceptibility
•Unlike HA-MRSA, usually susceptible to
antibiotics other than vancomycin
•Typically also susceptible to
• Clindamycin (!inducible resistance!)
• TMP/SMX
• Gentamicin
• Erythromycin
• Fluoroquinolones
Barton M et al.
Can J Infect Dis Med Microbiol 2006; 17(Suppl C): 1B-24B
CA-MRSA risk factors
•Children less than 2 years old
•Minority populations:
• Native or Aboriginal
• African-American
•Athletes (mainly contact-sport participants)
•Injection drug users
•Men who have sex with men
•Military personnel
•Inmates of correctional facilities
•Veterinarians, pet owners and pig farmers
Barton M et al.
Can J Infect Dis Med Microbiol 2006; 17(Suppl C): 1B-24B
MRSA pneumonia in children:
When to suspect…
• For children hospitalized with severe CAP empiric
therapy for MRSA is recommended (pending
sputum and/or blood culture results):
• Those requiring an intensive care unit (ICU)
admission,
• OR Necrotizing or cavitary infiltrates,
• OR Empyema
Lui C, et al. Clin Infect Dis. 2011;52:1-38
Management of CAP: Antibiotic therapy
MRSA susceptible to clindamycin
Parenteral therapy
• Preferred: vancomycin (40–60 mg/kg/day every
6–8 hours or dosing to achieve an AUC/MIC ratio of
>400) or clindamycin (40 mg/kg/day every 6–8
hours);
• Alternatives: linezolid (30 mg/kg/day every 8
hours for children ,12 years old and 20 mg/kg/day
every 12 hours for children $12 years old)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
MRSA susceptible to clindamycin
Oral therapy
• Preferred: oral clindamycin (30–40 mg/kg/day in
3 or 4 doses);
• Alternatives: oral linezolid (30 mg/kg/day in 3
doses for children >12 years and 20 mg/kg/day in
2 doses for children ≥12 years)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
MRSA resistant to clindamycin
Parenteral therapy
• Preferred: vancomycin (40–60 mg/kg/day every
6-8 hours or dosing to achieve an AUC/MIC ratio of
>400);
• Alternatives: linezolid (30 mg/kg/day every 8
hours for children <12 years old and 20 mg/kg/day
every 12 hours for children ≥12 years old)
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Management of CAP: Antibiotic therapy
MRSA resistant to clindamycin
Oral therapy
• Preferred: oral linezolid (30 mg/kg/day in 3 doses
for children <12 years and 20 mg/kg/day in 2
doses for children ≥12 years old);
• Alternatives: none; entire treatment course with
parenteral therapy may be required
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
MRSA pneumonia in children
Vancomycin Dosing in Children
• Vancomycin 15 mg/kg/dose every 6 h (60
mg/kg/day) is recommended for serious or invasive
disease (data are limited to guide vancomycin
dosing in children).
• Trough concentrations of 15–20 mcg/mL should
be considered in those with serious infections,
such as bacteremia, infective endocarditis,
osteomyelitis, meningitis, pneumonia, and
severe SSTI (eg, necrotizing fasciitis)
• The efficacy and safety of this dose requires
additional study
Lui C, et al. Clin Infect Dis. 2011;52:1-38
MRSA pneumonia in children
Adjunctive therapy for MRSA
• Not routinely recommended: Protein synthesis
inhibitors (eg, clindamycin and linezolid) and
intravenous immunoglobulin (IVIG)
• Some experts may consider these agents in
selected scenarios (eg, necrotizing pneumonia or
severe sepsis)
Lui C, et al. Clin Infect Dis. 2011;52:1-38
Management of CAP: Antibiotic therapy
for other etiologic agents
The guideline offers specific therapy
recommendations for pediatric CAP caused by
•MSSA…
•H. influenzae, typable or not
•Chlamydia & Chlamydophila
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Empyema
Empyema: definition
• Empyema is inflammatory fluid and debris in the
pleural space. It results from an untreated pleuralspace infection that progresses from free-flowing
pleural fluid to a complex collection in the pleural
space.
Pathophysiology
• Exudative stage
• Fibrinolytic stage
• Organization stage
Epidemiology
• Increase in incidence since the mid-nineties (USA)
• Particularly among certain age groups
Gupta R. Crowley S. Thorax 2006; 61:179-180
Gupta R. Crowley S. Thorax 2006; 61:179-180
Finlay C et al. Can Respir J 2008
Finlay C et al. Can Respir J 2008
Finlay C et al. Can Respir J 2008
Finlay C et al. Can Respir J 2008
Finlay C et al. Can Respir J 2008
Variables associated with
parapneumonic effusions
• Pneumococcal serotype? NO
• Age ≥ 3 years (p<0,0001)*
• Varicella (p<0,0001)*
• Fever ≥ 7 days (p<0,0001)*
• Medication use:
• Ibuprofen (p<0,0001)*
• Ceftriaxone (p<0,0001)*
*: Multivariate regression analysis
Parapneumonic effusions management
Small effusions
• Size of effusion: Small: <10 mm on lateral
decubitus radiograph or opacifies less than onefourth of hemithorax
• Bacteriology: Bacterial culture and Gram stain
results unknown or negative
• Risk of poor outcome: Low
• Tube drainage: No; sampling of pleural fluid is not
routinely required
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Parapneumonic effusions management
Moderate effusions
• Size of effusion: Moderate: >10 mm rim of fluid
but opacifies less than half of the hemithorax
• Bacteriology: Bacterial culture and/or Gram stain
results negative or positive (empyema)
• Risk of poor outcome: Low to moderate
• Tube drainage:
• No, if the patient has no respiratory
compromise and the pleural fluid is not
consistent with empyema;
• Yes, if the patient has respiratory compromise
or if pleural fluid is consistent with empyema
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Parapneumonic effusions management
Large effusions
• Size of effusion: Large: opacifies more than half of
the hemithorax
• Bacteriology: Bacterial culture and/or Gram stain
results positive (empyema)
• Risk of poor outcome: High
• Tube drainage: Yes, in most cases
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Parapneumonic effusions management
Antibiotic therapy
• In the case of culture-negative parapneumonic
effusions, antibiotic selection should be based on
the treatment recommendations for patients
hospitalized with CAP
• The duration of antibiotic treatment depends on the
adequacy of drainage and on the clinical response
demonstrated for each patient. In most children,
antibiotic treatment for 2–4 weeks is adequate
IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25
Merci!
François Boucher
MD, FRCPC