Fran

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Community acquired pneumonia (CAP) Why is this
still a problem?

• François Boucher MD, FRCPC

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• The complete PowerPoint file of this presentation
  is available at the following URL
• http//tinyurl.com/7uc3m4e
• francois_at_boucher.cc

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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.

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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

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IDSA Pediatric Community Pneumonia Guidelines.
CID 201153e25
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Incidence in Canadian children

• 41,000 children lt5 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)

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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

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Pathogens in pediatric CAP
Pediatr Infect Dis J 2002 21 592-598
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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

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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

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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

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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

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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

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Management of CAPWhen to obtain a CXR

• Child lt 5 years of age with high fever and high
  WBC of uncertain source
• Ambiguous clinical findings
• Suspected complication, i.e. pleural effusion
• Pneumonia is prolonged and unresponsive to
  treatment

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Management of CAPConsiderations for admission

• Child aged less than 6 months of age
• Toxic appearance
• Severe respiratory difficulty
• TcSaO2 lt 95
• Dehydration, vomiting
• No response to oral medication
• Immunocompromised child
• Social circumstances / poor compliance

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IDSA Pediatric Community Pneumonia Guidelines.
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IDSA Pediatric Community Pneumonia Guidelines.
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Management of CAP Antibiotic therapyChild lt 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 25)
• 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.
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Management of CAP Antibiotic therapyChild 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.
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Management of CAP Antibiotic therapyChild 5
years old

• Presumed atypical pneumonia
• Oral azithromycin (10 mg/kg on day 1, followed by
  5 mg/kg/day once daily on days 25 to a maximum
  of 500 mg on day 1, followed by 250 mg on days
  25) alternatives oral clarithromycin (15
  mg/kg/day in 2 doses to a maximum of 1 g/day)
  erythromycin, doxycycline for children gt7 years
  old

IDSA Pediatric Community Pneumonia Guidelines.
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Management of CAP Antibiotic therapyInpatient
(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 201153e25
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Management of CAP Antibiotic therapyInpatient
(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 gt7 years old
  levofloxacin for children who have reached growth
  maturity, or who cannot tolerate macrolides

IDSA Pediatric Community Pneumonia Guidelines.
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Management of CAP Antibiotic therapyNot
completely immunized

• Presumed bacterial pneumonia
• Ceftriaxone or cefotaxime addition of vancomycin
  or clindamycin for suspected CA-MRSA
• alternative levofloxacin addition of vancomycin
  or clindamycin for suspected CA-MRSA

IDSA Pediatric Community Pneumonia Guidelines.
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Management of CAP Antibiotic therapyNot
completely immunized

• Presumed atypical pneumonia
• Azithromycin (in addition to ß-lactam, if
  diagnosis in doubt)
• alternatives clarithromycin or erythromycin
  doxycycline for children gt7 years old
  levofloxacin for children who have reached growth
  maturity or who cannot tolerate macrolides

IDSA Pediatric Community Pneumonia Guidelines.
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Management of CAP Antibiotic therapyMild 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
  (1620 mg/kg/day in 2 doses for children 6 months
  to 5 years old and 810 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 lt12 years old and 20 mg/kg/day
  in 2 doses for children 12 years old)

IDSA Pediatric Community Pneumonia Guidelines.
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Management of CAP Antibiotic therapyParenteral
therapy

• Preferred ampicillin (150200 mg/kg/day every 6
  hours) or penicillin (200 000250 000 U/kg/day
  every 46 h)
• Alternatives ceftriaxone (50100 mg/kg/day every
  1224 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 68 hours) or vancomycin (4060 mg/kg/day
  every 68 hours)

IDSA Pediatric Community Pneumonia Guidelines.
CID 201153e25
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Management of CAP Antibiotic therapyHighly
resistant S.pneumoniaeParenteral therapy

• Preferred ceftriaxone (100 mg/kg/day every 1224
  hours)
• Alternatives ampicillin (300400 mg/kg/day every
  6 hours), levofloxacin (1620 mg/kg/day every 12
  hours for children 6 months to 5 years old and
  810 mg/kg/day once daily for children 516 years
  old maximum daily dose, 750 mg), or linezolid
  (30 mg/kg/day every 8 hours for children lt12
  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 68 hours) or vancomycin (4060 mg/kg/day
  every 68 hours)

IDSA Pediatric Community Pneumonia Guidelines.
CID 201153e25
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Management of CAP Antibiotic therapyHighly
resistant S.pneumoniaeOral therapy

• Preferred oral levofloxacin (1620 mg/kg/day in
  2 doses for children 6 months to 5 years and 810
  mg/kg/day once daily for children 516 years,
  maximum daily dose, 750 mg), if susceptible, or
  oral linezolid (30 mg/kg/day in 3 doses for
  children lt12 years and 20 mg/kg/day in 2 doses
  for children 12 years)
• Alternative oral clindamycin (3040 mg/kg/day in
  3 doses)

IDSA Pediatric Community Pneumonia Guidelines.
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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

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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
• gt 2 weeks neuropathy, lactic acidosis,
  mitochondrial toxicity

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Management of CAP Antibiotic therapyGroup A
StreptococcusParenteral therapy

• Preferred intravenous penicillin (100 000250
  000 U/kg/day every 46 hours) or ampicillin (200
  mg/kg/day every 6 hours)
• Alternatives ceftriaxone (50100 mg/kg/day every
  1224 hours) or cefotaxime (150 mg/kg/day every 8
  hours)
• may also be effective clindamycin, if
  susceptible (40 mg/kg/day every 68 hours) or
  vancomycin (4060 mg/kg/day every 68 hours)

IDSA Pediatric Community Pneumonia Guidelines.
CID 201153e25
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Management of CAP Antibiotic therapyGroup A
StreptococcusOral therapy

• Preferred amoxicillin (5075 mg/kg/day in 2
  doses), or penicillin V (5075 mg/kg/day in 3 or
  4 doses)
• Alternative oral clindamycin (40 mg/kg/day in 3
  doses)

IDSA Pediatric Community Pneumonia Guidelines.
CID 201153e25
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Management of CAP Antibiotic therapyMycoplasma
pneumoniaeParenteral 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 201153e25
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Management of CAP Antibiotic therapyMycoplasma
pneumoniaeOral therapy

• Preferred azithromycin (10 mg/kg on day 1,
  followed by 5 mg/kg/day once daily on days 25)
• Alternatives clarithromycin (15 mg/kg/day in 2
  doses) or oral erythromycin (40 mg/kg/day in 4
  doses)
• for children gt7 years old, doxycycline (24
  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.
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Pneumonia caused by MRSA

• François Boucher MD, FRCPC

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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
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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
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MRSA pneumonia in childrenWhen 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. 2011521-38
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Management of CAP Antibiotic therapyMRSA
susceptible to clindamycinParenteral therapy

• Preferred vancomycin (4060 mg/kg/day every 68
  hours or dosing to achieve an AUC/MIC ratio of
  gt400) or clindamycin (40 mg/kg/day every 68
  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 201153e25
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Management of CAP Antibiotic therapyMRSA
susceptible to clindamycinOral therapy

• Preferred oral clindamycin (3040 mg/kg/day in 3
  or 4 doses)
• Alternatives oral linezolid (30 mg/kg/day in 3
  doses for children gt12 years and 20 mg/kg/day in
  2 doses for children 12 years)

IDSA Pediatric Community Pneumonia Guidelines.
CID 201153e25
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Management of CAP Antibiotic therapyMRSA
resistant to clindamycinParenteral therapy

• Preferred vancomycin (4060 mg/kg/day every 6-8
  hours or dosing to achieve an AUC/MIC ratio of
  gt400)
• Alternatives linezolid (30 mg/kg/day every 8
  hours for children lt12 years old and 20 mg/kg/day
  every 12 hours for children 12 years old)

IDSA Pediatric Community Pneumonia Guidelines.
CID 201153e25
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Management of CAP Antibiotic therapyMRSA
resistant to clindamycinOral therapy

• Preferred oral linezolid (30 mg/kg/day in 3
  doses for children lt12 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.
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MRSA pneumonia in childrenVancomycin 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 1520 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. 2011521-38
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MRSA pneumonia in childrenAdjunctive 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. 2011521-38
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Management of CAP Antibiotic therapyfor other
etiologic agents

• The guideline offers specific therapy
  recommendations for pediatric CAP caused by
• GAS
• MSSA
• H. influenzae, typable or not
• Chlamydia Chlamydophila
• Etc

IDSA Pediatric Community Pneumonia Guidelines.
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Empyema
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Empyema definition

• Empyema is inflammatory fluid and debris in the
  pleural space. It results from an untreated
  pleural-space infection that progresses from
  free-flowing pleural fluid to a complex
  collection in the pleural space.

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Pathophysiology

• Exudative stage
• Fibrinolytic stage
• Organization stage

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Epidemiology

• Increase in incidence since the mid-nineties
  (USA)
• Particularly among certain age groups

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Gupta R. Crowley S. Thorax 2006 61179-180
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Gupta R. Crowley S. Thorax 2006 61179-180
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Finlay C et al. Can Respir J 2008
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Finlay C et al. Can Respir J 2008
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Finlay C et al. Can Respir J 2008
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Finlay C et al. Can Respir J 2008
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Finlay C et al. Can Respir J 2008
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Variables associated with parapneumonic effusions

• Pneumococcal serotype? NO
• Age 3 years (plt0,0001)
• Varicella (plt0,0001)
• Fever 7 days (plt0,0001)
• Medication use
• Ibuprofen (plt0,0001)
• Ceftriaxone (plt0,0001)

Multivariate regression analysis
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Parapneumonic effusions managementSmall effusions

• Size of effusion Small lt10 mm on lateral
  decubitus radiograph or opacifies less than
  one-fourth 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.
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Parapneumonic effusions managementModerate
effusions

• Size of effusion Moderate gt10 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.
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Parapneumonic effusions managementLarge 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.
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Parapneumonic effusions managementAntibiotic
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 24 weeks is
  adequate

IDSA Pediatric Community Pneumonia Guidelines.
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Merci!

• François Boucher MD, FRCPC

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How is antimicrobial sensitivity measured in the
lab?
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Kirby-Bauer Disk-Diffusion test
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E-Test (Epsilometer)

• This Etest strip contains graduated
  concentrations of ampicillin ranging from 0.016
  µg/ml (not shown) to 256 µg/ml placed on an agar
  plate growing Escherichia coli. Since the
  intersection of the growth-inhibition margin lies
  between two minimum inhibitory concentrations
  (MICs)0.38 and 0.5 µg/mlthe test is interpreted
  at the highest value (0.5 µg/ml). This organism
  is defined as susceptible since the MIC lies
  below the breakpoint of 8 µg/ml or lower.

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MIC testingwith the broth-dilution technique
On dilue lantibiotique dans des tubes
successifs On incube les bactéries pendant 24
heures
Après 24 heures, on observe une
croissance Bactérienne dans certains tubes
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MBC determination
Après 24 heures, on observe une croissance sur
certains milieux
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D-test for inducible resistance to clindamycin
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D-test for inducible clindamycin resistance in
MRSA
Pictures James H. Brien, DO Pediatric Infectious
Disease, Texas AM University
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D-test for inducible clindamycin resistance in
MRSA

• Positive double disk diffusion test (D-Test)
  shows induction of clindamycin (CC) resistance by
  erythromycin (E) in this methicillin-resistant
  Staphylococcus aureus isolate. This is indicated
  by the blunting of the clindamycin zone of
  inhibition, which appears as a D shape.