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Infectious Disorders of the Lung Parenchyma. Matthew L. Paden, MD Pediatric Critical Care Fellow Emory University Children’s Healthcare of Atlanta at Egleston. Objectives. Worldwide epidemiology of the problem Review common etiologies Discuss empirical and disease specific treatment.

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infectious disorders of the lung parenchyma

Infectious Disorders of the Lung Parenchyma

Matthew L. Paden, MD

Pediatric Critical Care Fellow

Emory University

Children’s Healthcare of Atlanta at Egleston

objectives
Objectives
  • Worldwide epidemiology of the problem
  • Review common etiologies
  • Discuss empirical and disease specific treatment
epidemiology
Epidemiology
  • World wide
    • Leading cause of death in children
    • More than AIDS, malaria, and measles combined
    • Most deaths in < 5 yo
  • United states
    • 3rd leading cause of hospitalization for kids
    • 2% of deaths (5% including neonates)
http www who int child adolescent health publications child health isbn 92 806 4048 8 htm
http://www.who.int/child-adolescent-health/publications/CHILD_HEALTH/ISBN_92_806_4048_8.htmhttp://www.who.int/child-adolescent-health/publications/CHILD_HEALTH/ISBN_92_806_4048_8.htm
worldwide epidemiology
Worldwide Epidemiology
  • Cases
    • 150 million
  • Hospitalizations
    • 11-20 million
  • Deaths
    • 2 million
barriers to care
Barriers to care
  • Recognizing there is a problem
  • Seek appropriate care
  • Treatment with antibiotics
prevention
Prevention
  • Adequate nutrition
    • Exclusive breastfeeding
      • Less than 1 yo, get any formula – 5 X increased risk of death from pneumonia
    • Zinc supplementation
prevention1
Prevention
  • Immunization
    • Measles –
      • Pneumonia is what they die of – often super-infection
      • World-wide coverage rate – 76% in 2004
      • Still having 30-40 million cases a year
    • HIB –
      • 2-3 million cases of severe disease a year
      • In 2003, developed world coverage – 92%
      • Developing world – 42%
      • Least developed countries – 8%
prevention2
Prevention
  • Immunization
    • Strep pneumo –
      • 7 –valent vaccine (Prevnar) in the US
      • 9, 11, or 13 valent vaccine for the rest of the world
      • Gambia – 17,000 children
        • 37% reduction in pneumonia
        • 15% reduction in hospitalization
        • 16% reduction in mortality
costs involved
Costs involved
  • More than 1 million deaths a year can be prevented with treatment and prevention
  • 600,000 lives saved by just treatment alone
  • Cost analysis
    • Antibiotic treatment course-
      • $ 0.27
    • $ 600 million total cost including :
      • Cost of antibiotics
      • Cost of hospital stays
      • Increasing training of health care staff
      • Increasing physical plants to take care of these patients
costs involved1
Costs involved
  • Those costs inflated by Mexico and Brazil
  • 85% of deaths are in sub-Saharan Africa and southeast Asia
    • $200 million dollars will expand coverage to those regions only and potentially fix 85% of the problem
potential solutions
Potential solutions
  • One F-22 fighter - $183 million
  • 1997-2003, Defense Department purchased and then left unused approximately 270,000 fully refundable commercial airline tickets at a total cost of $100 million.
  • $4,000,000 for the Northern Line Extension
    • A direct 82 mile train route from North Pole (pop. 1,778 in 2005) to Delta Junction (pop. 840 in 2000)
  • $9,500,000 for the Extended Cold Weather Clothing System
  • $8,000,000 added by the Senate for special assistance DOD Dependents Education.
  • $5,500,000 for The Ernest Gallo Clinic and Research Center at (USCF) to study basic neuroscience and the effects of alcohol and drug abuse on the brain.”
  • $1,650,000 to improve the shelf life of vegetables “This project will help our troops in the field get fresh tomatoes…”
diagnosis
Diagnosis
  • Tachypnea
    • Sensitive but not specific
  • Higher specificity
    • Decreased breath sounds
    • Inspiratory rales
    • Chest wall retractions
    • Nasal flaring
  • Absence of fever has high negative predictive value for bacterial pneumonia
etiologies
Etiologies
  • Streptococcus pneumoniae
    • Most common cause outside of neonatal period
    • Nasopharyngeal colonization – 50% of kids
    • >90 serotypes – majority of invasive disease caused by 10 serotypes
    • Bacteremia in 25-30% of kids
    • Gram stain – gram positive lancet shaped diplococci (“gram positive cocci in pairs”)
age differences
Age differences
  • Adults – lobar pneumonia
  • Kids – lobar or bronchopneumonia
treatment streptococcus pneumoniae
Treatment - Streptococcus pneumoniae
  • 2002 CDC Surveillance data
    • 20% PCN resistant
    • 4% Cefotaxime resistant
    • 0% Vancomycin resistant
  • 2003-2004 FAST Surveillance data
    • 56% PCN resistant
slide17

Geographically-based evaluation of multi-drug resistance trends among Streptococcus pneumoniae in the USA: findings of the FAST surveillance initiative (2003-2004). Int J Antimicrob Agents. 2006 Dec;28(6):525-31.

2006 choa data
2006 CHOA Data

Percent of organisms tested that have intermediate or resistant sensitivity patterns

treatment strep pneumo
Treatment – Strep pneumo
  • Mechanism of resistance –
    • PCN and Cephalosporins – change in penicillin binding proteins (NOT beta lactamase)
  • Empiric : 3rd generation cephalosporin + vancomycin until sensitivities are confirmed
etiologies1
Etiologies
  • Staphylococcus aureus
    • Common cause of ventilator associated and nosocomial pneumonia
    • Community acquired disease usually coincident with viral infection (influenza)
      • Viral hemagglutinins – inhibit neutrophil and monocyte activation
    • Gram stain – gram positive cocci in grape like clusters
diagnosis staphylococcal pneumonia
Diagnosis – Staphylococcal pneumonia
  • Classically a lobar consolidation on CXR
  • Raise suspicion of staph
    • Pneumatoceles
    • Pleural effusion
    • Air fluid levels
    • Necrosis
treatment staphylococcus aureus
Treatment – Staphylococcus aureus
  • Treatment has changed over the past 5 years with emergence of caMRSA
  • Empiric therapy with Vancomycin
    • VISA (1996, Japan, 1997 US)
      • Mechanism – thickening of cell membrane – decreased penetration of vancomycin – unclear mechanism
    • VRSA (2002, US)
      • Mechanism – VanA from enterococcus – changes d-alanine, d-alanine terminus to d-alanine, d-lactate – reduces affinity by 1,000 fold
    • VDSA
2006 choa data1
2006 CHOA Data
  • ECH total % MRSA 53% SRH total % MRSA 51%

* Not adjusted for inducible resistance

staph aureus treatment
Staph Aureus treatment
  • Get off Vancomycin if MSSA
    • MSSA much more susceptible to Nafcillin
    • Use of Vancomycin or first-generation Cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia. Clin Infect Dis. 2007 Jan 15;44(2):190-6.
      • Treatment failure - Vancomycin 31.2% vs. Ancef 13% ; p=.02
      • Multivariable analysis - factors independently associated with treatment failure included Vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15-13.45)
staph aureus treatment1
Staph aureus treatment
  • Get off Vancomycin if MSSA
    • Staphylococcus aureus bacteremia and endocarditis: the Grady Memorial Hospital experience with methicillin-sensitive S aureus and methicillin-resistant S aureus bacteremia. Am Heart J. 2004 Mar;147(3):536-9.
      • MSSA bacteremia is associated with higher rates of endocarditis than MRSA.
    • Comparative activity of cloxacillin and vancomycin against methicillin-susceptible Staphylococcus aureus experimental endocarditis.J Antimicrob Chemother. 2006 Nov;58(5):1066-9.
      • Cloxacillin produced a greater decrease in the number of staphylococci than vancomycin
      • 41% of rabbits had sterile vegetations in comparison with 0% with vancomycin (p=0.035)
new horizons
New horizons
  • Anti-MRSA beta-lactams in development, with a focus on ceftobiprole: the first anti-MRSA beta-lactam to demonstrate clinical efficacy. Expert Opin Investig Drugs. 2007 Apr;16(4):419-29.
    • Investigational beta-lactam antibiotic against methicillin-resistant staphylococci, enterococcus faecalis, penicillin-resistant streptococci and many Gram-negative pathogens.
    • Completed Phase III therapeutic trials
  • PPI0903 - injectable pro-drug of a broad-spectrum cephalosporin with anti-MRSA activity
  • RO4908643 - a carbapenem with anti-MRSA activity
etiologies2
Etiologies
  • Pseudomonas aeruginosa
    • Common cause of bacterial nosocomial pneumonia
    • More common in CF, tracheostomy dependant, or immunocompromised
    • Oxidase positive gram negative rod
pseudomonas treatment
Pseudomonas treatment
  • Antibiotic resistance common
    • Mechanism – extended spectrum beta-lactamase
    • Implication – serious or life-threatening infections should not be treated with an anti-pseudomonal synthetic penicillin/cephalosporin/carbapenem alone
  • Empiric therapy – anti-pseudomonal PCN + an aminoglycoside
    • Role of monotherapy has not been well defined.
pseudomonas treatment1
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
      • Ticarcillin +/- clavulanate
      • Piperacillin +/- tazobactam
pseudomonas treatment2
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
      • Ticarcillin +/- clavulanate
      • Piperacillin +/- tazobactam
    • Mechanism of Action
      • Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins
      • Inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls
      • Clavulanate and tazobactam prevents degradation of the PCN by binding to beta-lactamases
pseudomonas treatment3
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
    • 4th generation cephalosporin – cefepime
      • Ceftazidime – 2nd generation with pseudomonas activity
pseudomonas treatment4
Pseudomonas treatment
  • Antibiotic choices
    • 4th generation cephalosporin – cefepime
    • Mechanism of Action
      • Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins
      • Inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls
pseudomonas treatment5
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
    • 4th generation cephalosporin – cefepime
    • Carbapenems – imipenem-cilastatin or meropenem
pseudomonas treatment6
Pseudomonas treatment
  • Antibiotic choices
    • Carbapenems – imipenem-cilastatin or meropenem
    • Mechanism of Action
      • Inhibits cell wall synthesis by binding to penicillin-binding proteins (PBPs) with its strongest affinities for PBPs 2, 3 and 4 of E. coli and P. aeruginosa and PBPs 1, 2 and 4 of S. aureus
      • Meropenem reduces valproate levels by ~40%
pseudomonas treatment7
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
    • 4th generation cephalosporin – cefepime
    • Carbapenems – imipenem-cilastatin or meropenem
    • Aztreonam
pseudomonas treatment8
Pseudomonas treatment
  • Antibiotic choices
    • Aztreonam
    • Mechanism of Action
      • Binds to penicillin-binding protein 3 which produces filamentation of the bacterium inhibiting bacterial cell wall synthesis and causing cell wall destruction
pseudomonas treatment9
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
    • 4th generation cephalosporin – cefepime
    • Carbapenems – imipenem-cilastatin or meropenem
    • Aztreonam
    • Fluroquinolones – ciprofloxacin, levofloxacin, etc.
pseudomonas treatment10
Pseudomonas treatment
  • Antibiotic choices
    • Fluroquinolones – ciprofloxacin, levofloxacin, etc.
    • Mechanism of Action
      • Inhibits DNA-gyrase and topoisomerase IV in susceptible organisms; inhibits relaxation of supercoiled DNA and promotes breakage of double-stranded DNA
pseudomonas treatment11
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
    • 4th generation cephalosporin – cefepime
    • Carbapenems – imipenem-cilastatin or meropenem
    • Aztreonam
    • Fluroquinolones – ciprofloxacin, levofloxacin, etc.
    • Aminoglycosides – amikacin, gentamicin, tobramycin
pseudomonas treatment12
Pseudomonas treatment
  • Antibiotic choices
    • Aminoglycosides – amikacin, gentamicin, tobramycin
    • Mechanism of Action
      • Inhibits cellular initiation of bacterial protein synthesis by binding to 30S and 50S ribosomal subunits resulting in a defective bacterial cell membrane
pseudomonas treatment13
Pseudomonas treatment
  • Antibiotic choices
    • Anti-pseudomonal synthetic penicillin
    • 4th generation cephalosporin – cefepime
    • Carbapenems – imipenem-cilastatin or meropenem
    • Aztreonam
    • Fluroquinolones – ciprofloxacin, levofloxacin, etc.
    • Aminoglycosides – amikacin, gentamicin, tobramycin

So which to choose?

2006 choa data pseudomonas
2006 CHOA Data - Pseudomonas

* No CF patients included

2006 choa data pseudomonas1
2006 CHOA Data - Pseudomonas

* No CF patients included

etiologies3
Etiologies
  • “Atypical” Pneumonias
    • Mycoplasma pneumoniae
    • Chlamydia pneumoniae
    • Legionella pneumophilia
  • Common cause of pneumonia in school age children
    • Persistent cough (for weeks after infection has cleared)
atypical pneumonia diagnosis
“Atypical” Pneumonia diagnosis
  • Mycoplasma – clinical picture + serologic testing
    • Cold agglutinins are not specific
    • Complications – arthritis, hemolysis, pericardial effusions, myocarditis, encephalitis, Stevens-Johnson syndrome
      • Antibiotic therapy has not been conclusively shown to help non-pulmonary manifestations
atypical pneumonia diagnosis1
“Atypical” Pneumonia diagnosis
  • Legionella pneumophilia
    • Severe disease in immunocompromised
      • Respiratory failure, pericarditis
    • Classic history triggers – exposure to travel, hot tubs, or hospitalization
    • DFA, culture, and serology available
    • Urinary antigen – good sensitivity and specificity
atypical pneumonia treatment
“Atypical” Pneumonia treatment
  • Macrolide antibiotics
    • Erythromycin
    • Azithromycin
  • Mechanism of Action
    • Inhibits bacterial RNA-dependent protein synthesis by binding to the 50S ribosomal subunit which results in the blockage of transpeptidation
etiologies4
Etiologies
  • Viral
    • Respiratory syncytial virus
    • Parainfluenza
    • Influenza
    • Adenovirus
    • Human metapneumovirus
    • Hantavirus
respiratory syncytial virus
Respiratory syncytial virus
  • Enveloped, single stranded, negative polarity RNA paramyxovirus
  • Seasonality – November through May
respiratory syncytial virus diagnosis
Respiratory syncytial virus diagnosis
  • Viral culture is gold standard
  • DFA and PCR available
  • PICU presentation
    • Upper airway obstruction
    • Lower airway obstruction
    • Pneumonia
    • Apnea
respiratory syncytial virus diagnosis1
Respiratory syncytial virus diagnosis
  • Upper airway obstruction
    • Laryngotracheobronchitis
      • If fails traditional management (steroids, oxygen, epinephrine, heliox, etc.) and is intubated get endotracheal aspirate for bacterial superinfection
        • Often staph or strep
respiratory syncytial virus diagnosis2
Respiratory syncytial virus diagnosis
  • Lower airway obstruction
    • Clinically bronchiolitis
    • Increasing airway edema and mucous secretion worsen the obstruction
    • CXR confirms hyperinflation and patchy infiltrates
    • Intubated patients commonly co-infected with moraxella
respiratory syncytial virus treatment
Respiratory syncytial virus treatment
  • Lower airway obstruction
    • Treatment –
      • Oxygen
      • +/- nebulized B-agonists or epinephrine
      • +/- nasal suctioning
      • +/- vasoconstrictive nasal drops
      • +/- NIPPV
      • Mechanical ventilation based on reduction of obstruction
        • Lower rates and maximizing expiratory time
respiratory syncytial virus treatment1
Respiratory syncytial virus treatment
  • Lower airway obstruction
    • Treatment –
      • Steroids – RSV alone, no efficacy in reducing stay
      • Ribivirin – only FDA approved drug for RSV
        • Many complications and expensive
        • May have a role in the immunocompromised
respiratory syncytial virus diagnosis3
Respiratory syncytial virus diagnosis
  • RSV Pneumonia
    • Similar presentation as bronchiolitis
    • Different pathophysiology – alveolar filling and consolidation
    • CXR
      • Discrete infiltrate and lack of hyperinflation
    • Greater degree of hypoxia
    • More likely to progress to ARDS
respiratory syncytial virus diagnosis4
Respiratory syncytial virus diagnosis
  • RSV Apnea
    • Not well described
    • More common with increasing prematurity
    • Polysomnography implies it is central apnea
    • Pathophysiology – signaling from pulmonary nerves through the GABA and substance P pathways
      • Pediatr Res. 2005 Jun;57(6):819-25.
etiologies5
Etiologies
  • Viral
    • Respiratory syncytial virus
    • Parainfluenza
    • Influenza
    • Adenovirus
    • Human metapneumovirus
    • Hantavirus
parainfluenza diagnosis
Parainfluenza diagnosis
  • Enveloped, single stranded, negative polarity RNA paramyxovirus
  • Similar presentations to RSV
  • Viral culture is gold standard
  • DFA or PCR available
  • 4 different virus types
    • Type 1 epidemic every other year
parainfluenza treatment
Parainfluenza treatment
  • Similar supportive care to RSV
  • May be a role for both inhaled and intravenous ribivirin in immunosuppressed patients
etiologies6
Etiologies
  • Viral
    • Respiratory syncytial virus
    • Parainfluenza
    • Influenza
    • Adenovirus
    • Human metapneumovirus
    • Hantavirus
influenza diagnosis
Influenza diagnosis
  • Negative sense, single stranded RNA viruses
  • Type A and B responsible for majority of illnesses
  • Hemagglutinin – viral binding to respiratory epithelial cells vial sialic acid
  • Neuroaminidase – cleaves sialic acid residues once virus has multiplied in the cell allowing viral spread
influenza diagnosis1
Influenza diagnosis
  • Clinical markers
  • Other manifestations
    • Laryngotracheobronchitis
    • Myocarditis
    • Rhabdomyolysis
    • Reye’s syndrome
    • Encephalitis
    • Staph superinfection
influenza diagnosis2
Influenza diagnosis
  • Viral culture is gold standard
  • DFA, PCR, and rapid immunoassays available
influenza treatment
Influenza treatment
  • Amantidine or rimantidine
    • Inhibits influenza M2 proteins and prevent viral uncoating
    • Need to give early or no benefit
    • Resistance is documented
  • Oseltamivir and zanamivir
    • Neuroaminidase inhibitors
etiologies7
Etiologies
  • Viral
    • Respiratory syncytial virus
    • Parainfluenza
    • Influenza
    • Adenovirus
    • Human metapneumovirus
    • Hantavirus
adenovirus diagnosis
Adenovirus diagnosis
  • Specifically types 3 and 7
  • Rapidly evolving life threatening pneumonia with necrosis, pulmonary hemorrhage and bronchiolitis obliterans
  • Survival dependant on degree of injury
  • Viral culture is gold standard
  • DFA, PCR, rapid ELISA are available
  • ECLS an option
    • Extracorporeal life support for the treatment of viral pneumonia: collective experience from the ELSO registry. Extracorporeal Life Support Organization. J Pediatr Surg. 1997 Feb;32(2):232-6.
etiologies8
Etiologies
  • Viral
    • Respiratory syncytial virus
    • Parainfluenza
    • Influenza
    • Adenovirus
    • Human metapneumovirus
    • Hantavirus
human metapneumovirus diagnosis
Human metapneumovirus diagnosis
  • Also a paramyxovirus
  • In children and infants notable cause of lower respiratory tract infections
    • Bronchiolitis (59%)
    • Croup (18%)
    • Asthma exacerbations (14%)
    • Pneumonia (8%).
  • Symptoms very similar to RSV (cough 90%;

dyspnea 83%; coryza 88%; fever 52-92%)

  • Can cause severe disease in BMT patients
  • PCR based diagnosis at this point
  • Supportive treatment
etiologies9
Etiologies
  • Viral
    • Respiratory syncytial virus
    • Parainfluenza
    • Influenza
    • Adenovirus
    • Human metapneumovirus
    • Hantavirus
hantavirus diagnosis
Hantavirus diagnosis
  • A negative sense, single stranded RNA virus of the bunyaviridae family
  • Multiple different viruses worldwide
  • Four corners region - Sin Nombre virus
  • All other bunyaviridae have arthropod vectors
    • Hantavirus – vector is the deer mouse
  • 8% of hantavirus infections in US are children
    • 33% mortality (similar to adults)
hantavirus infection
Hantavirus infection
  • Exposure/Travel history
  • Clinical syndrome
    • Fever
    • Fulminant bilateral pulmonary disease
    • Cardiogenic shock
    • Pulmonary edema
hantavirus diagnosis1
Hantavirus diagnosis
  • Laboratory syndrome
    • Hemoconcentration
    • Thrombocytopenia
    • Leukocytosis
    • Absence of granules in neutrophils
    • Immunoblasts on smear
hantavirus diagnosis2
Hantavirus diagnosis
  • Laboratory syndrome
    • Testing via serologies, immunohistochemistry, and rapid RNA PCR
    • All via New Mexico/CDC
  • Treatment –
    • Study with IV Ribavirin via UNM/CDC
    • Supportive
hantavirus treatment
Hantavirus treatment
  • Above all – Consultation with experts at University of New Mexico and CDC
  • From CDC Website :
    • Take-home Message for Care ProvidersRapid transfer to ICUCareful monitoringFluid balanceElectrolyte balance Blood pressure
hantavirus treatment1
Hantavirus treatment
  • Management with Swan-Ganz catheter essential
    • In contrast to septic shock, HPS patients have a low cardiac output with a raised systemic vascular resistance.
    • Titrate fluid to keep wedge pressure to <12
    • Poor prognostic indicators include a plasma lactate of greater than 4.0 mmol/L or a cardiac index of less than 2.2 L/min/m2
    • Whilst pulmonary edema and pleural effusions are common, multiorgan dysfunction syndrome is rarely seen.
hantavirus treatment2
Hantavirus treatment
  • Prior to the use of extracorporeal membrane oxygenation (ECMO) as a rescue therapy, a cardiac index of less than 2.5 L/min/m2 predicted 100% mortality rate.
  • eMedicine – 15 patients, 9 intact survivors
  • Dramatic improvement usually seen in the first day
  • Runs are usually 4-5 days
etiologies10
Etiologies
  • Fungal Pneumonias
    • Candida
    • Aspergillus
candida pneumonia diagnosis
Candida pneumonia diagnosis
  • Essentially a disease of immuno-compromised
  • Common upper airway and oral flora
    • Colonization vs. infection
  • Translocation across the gut -> hematogenous spread to the lungs is another source in neutropenic patients
candida pneumonia diagnosis1
Candida pneumonia diagnosis
  • ECH Procedure
    • Sensitivity done automatically on all sterile site specimens
    • Can be done request on others (ETT is NOT sterile)
    • Done at SRH –
      • 48 hour test – must be done on a 48 hour old sample
      • Must be set up in the morning
      • Don’t set it up on the weekend
candida pneumonia diagnosis2
Candida pneumonia diagnosis
  • Multiple species
    • C. albicans
      • Most common
      • Quickest of the yeast to be identified – candida chrome agar (green color change)
candida chrome agar
Candida Chrome Agar
  • Produces species specific colorful colonies of Candida species.
  • Green: C. albicansBlue: C. tropicalisPink: C. krusei
candida pneumonia diagnosis3
Candida pneumonia diagnosis
  • Multiple species
    • C. albicans
      • Most common
      • Quickest of the yeast to be identified – candida chrome agar (green color change)
    • C. parapsilosis
      • Second most common at ECH
    • C. glabrata, krusei, lusitaniea
      • More rare, but the ones to worry about
antifungal therapy
Antifungal Therapy
  • Not a lot of good, large number trials in pediatric immuno-suppressed patients
  • Even less in treating pneumonia
    • Assume systemic spread in neutropenic patients
antifungal therapy1
Antifungal Therapy
  • Mostly C. albicans fungemia in non-neutropenics
  • Flu (400/d) vs. AmB (0.5-0.6 mg/kg/d). %Success:
    • Randomized, N=206, Flu 70%, AmB 79%, P = 0.22
    • Randomized, N=103, Flu 56%, AmB 60%, P = 0.80
    • Observational, N=294, Flu 73%, AmB 69%, P = 0.58
    • Observational, N=479, Flu 71%, AmB 73%, P > 0.38
  • ABLC (5 mg/kg/d) vs. AmB (0.6-1 mg/kg/d)
    • Randomized, N=194, ABLC 65%, AmB 61%, P = 0.64

Rex, 1994; Phillips 1997; Nguyen, 1995; Anaissie, 1998

candida sensitivities
Candida sensitivities

Flucon Itra AmB 5-FC

C. albicans S S S S

C. parapsilosis S S S S

C. tropicalisS S S S

C. glabrata SDD-R SDD-R IS

C. krusei RSDD-R I-r I-R

C. lusitaniae S S-SDDR R

aspergillus pneumonia
Aspergillus pneumonia
  • Organism – Aspergillus fumigatus
  • Increasing incidence in immuno-compromised patients
  • Solid organ or BMT patients
    • Mortality approaches 75%
aspergillus pneumonia diagnosis
Aspergillus pneumonia diagnosis
  • Large areas of pulmonary necrosis
    • Can look like staph
  • Necrosis is because of direct blood vessel invasion by the organism and subsequent thrombosis
    • SAME PHYSIOLOGY AS A PULMONARY EMBOLUS
    • Wedge shaped emboli seen on CXR
    • Right heart strain less often
aspergillus pneumonia diagnosis1
Aspergillus pneumonia diagnosis
  • Fungal culture from BAL sample is gold standard
aspergillus pneumonia treatment
Aspergillus pneumonia treatment
  • Empiric therapy with amphoteracin-B or itraconazole
  • Lobectomy used if caught early and confined
  • Mortality remains high despite all treatment
etiologies11
Etiologies
  • Mycobacterium tuberculosis
tb diagnosis
TB diagnosis
  • Aerobic acid-fast bacilli
  • High index of suspicion
  • Exposure/risk factor history is key
    • Known TB cases
    • Incarceration (jail/prison)
    • Health care workers
    • Homeless/Community shelter
    • Immuno-compromised
    • Travel to/visitation from endemic areas (Grady)
    • Ask about BCG in immigrants
tb diagnosis1
TB diagnosis
  • Recovery from culture is gold standard
    • AFB stain and culture
  • PCR available
tb treatment
TB Treatment
  • Get ID involved for recs and follow-up
  • Isolation in negative pressure room
    • Patient with surgical mask for any transport
    • Parents to get CXR (surgical mask)
      • “When determining TB status on adult family members of inpatients with diagnosed or strongly suspected TB, external diagnostic resources (private physician, health department) are considered first.”
      • “When circumstances do not allow for this, Children’s will provide diagnostic services only and refer, if needed, for treatment of disease.”
      • Write an order – parents register – pay or SW - get CXR – Emory radiologists read it
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