pneumonia in the critical care setting laura loftis, m.d., m.s. associate professor of pediatrics...

Pneumonia in the Critical Care Setting

Laura Loftis, M.D., M.S.

Associate Professor of Pediatrics and Medical Ethics

Baylor College of Medicine

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Objectives

1. To review diagnostic criteria for pneumonia

2. To examine treatment algorithms for pneumonia

3. Upon completion, the learner will be able to identify controversies surrounding identification of ventilator associated pneumonia

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Categories of pneumonia

1. Community acquired pneumonia

2. Pneumonia in special populations‐ immunocompromised

‐ cystic fibrosis

‐ chronically ventilator dependent

3. Ventilator associated pneumonia (VAP)

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Guideline Eligibility Criteria:• Age ≥ 60 days to 17 years• Healthy children without underlying conditions• Clinical findings of CAP

Guideline Exclusion Criteria:• Aspiration• Recent hospitalization (< 7 days before the onset of illness)

Evidence-Based Outcomes Center Team:Quinn Franklin, MS, CCLS, Research SpecialistJennifer Nichols, MPH, Research SpecialistCharles Macias, MD, MPH, Director

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Clinical Indicators• May be subtle

• Fever

‐Young infants may have afebrile pneumonia related to Chlamydia trachomatis

‐may be the only sign of occult pneumonia in highly febrile young children

• Tachypnea

‐absence of tachypnea - single most valuable sign for excluding pneumonia

• Respiratory distress

‐Retractions, hypoxemia (< 90% sats on RA), irritability, nasal flaring

‐Grunting, when present, is a sign of severe disease and impending respiratory failure

• Cough

‐ may be minimal if primarily an alveolar process

Ann Emerg Med. 1999;33(2):166; JAMA 1998;279(4):308

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Clinical Indicators - Lung exam

• Crackles or rales

• Diminished breath sounds

• Wheezes

• more common in atypical or viral

• Pleural effusion - chest pain with splinting, dullness to percussion, distant breath sounds, pleural friction rub

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Academic Emergency Medicine, 1996: 3(5), 396

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Radiographic patterns

• Segmental consolidation - reasonably specific for bacterial pneumonia but lacks sensitivity

‐not always easy to distinguish from segmental collapse (atelectasis), which is apparent in about 25 percent of children with bronchiolitis

• In a study of 254 children with radiographically defined pneumonia, the etiology was determined in 215

‐The sensitivity and specificity of alveolar infiltrate for bacterial pneumonia were 72 and 51 percent, respectively

‐the sensitivity and specificity of interstitial infiltrates for viral pneumonia were 49 and 72 percent, respectively

Acta Paediatr. 1993;82(4):360; Pediatr Radiol. 1974;2(3):155.; J Paediatr Child Health. 1990;26(4):209; Pediatrics 1998;102(6):1369; Thorax. 2002;57(5):438; Thorax. 1981;36(6):469

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Alveolar – note airbronchograms Interstitial

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Lobar consolidation Atelectasis

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Pleural effusions

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RADIOLOGIC EVALUATION

• Not necessary to confirm the diagnosis of suspected CAP

‐in children with mild, uncomplicated lower respiratory tract infection who are well enough to be treated as outpatients

‐Radiographic findings are poor indicators of the etiologic diagnosis

‐Radiographic findings may lag behind the clinical findings

• For hospitalized children

‐ to assess for the presence of effusions or other complications

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Admission Criteria:

• Unable to tolerate oral fluids and medications; severely dehydrated

• Moderate or severe respiratory distress

• Failed outpatient antibiotic treatment

• Altered mental status

• Oxygen saturation consistently < 90%

• Unsafe to send home / poor follow-up

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CAP Pathogens

• S pneumoniae

‐Most common bacteria in all age groups

‐less commonly S aureus or group A strep

• "Atypical" bacterial pneumonia

‐Mycoplasma pneumoniae or Chlamydophila (formerly Chlamydia) pneumoniae

‐Preschool aged children had as many episodes of atypical bacterial LRIs as older children.

• Afebrile pneumonia of infancy

‐generally seen between two weeks and four months of life.

‐classically caused by C. trachomatis,

Clinical Infectious Diseases 2011: 53(7), e25-e76

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Pediatrics, 2004:113(4), 701-707.

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Pleural Effusion

• small, simple pleural effusions

‐ampicillin to cover S. pneumoniae.

• ill-appearing children or those with clinical deterioration

‐vancomycin and cefotaxime.

• complicated pleural effusion

‐Chest thoracostomy tube (with or without fibrinolytics) or VATS

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‐ cystic fibrosis



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Immunocompromised pt• humoral immune deficiencies with accompanying diminished opsonizing capacity

‐functional asplenia, hematopoietic malignancy, transplantation, or immunoglobulin deficiency

‐encapsulated bacteria Streptococcus pneumoniae

• decreased cell-mediated immunity or macrophage function

‐in patients receiving T-lymphocyte depleting therapies for rheumatologic diseases or inflammatory bowel disease.

‐intracellular organisms (eg, Mycobacteria, Legionella, Nocardia, Strongyloides)

‐infection due to yeasts (eg, Histoplasma, Cryptococcus) or molds (eg, Aspergillus)

• neutrophil dysfunction* / neutropenia / receiving glucocorticoids and/or T-cell suppression**

‐ chronic granulomatous disease*

‐organ transplant recipients who require long-term immune suppression **

‐Nocardia and nontuberculous mycobacteria

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Immunocompromised pt• Sequential infection

‐ Ex: viral infection preceding bacterial or fungal infection

• Multiple simultaneous infections

‐ Ex: dual infection with Pneumocystis jirovecii (formerly P. carinii) and cytomegalovirus

• Disseminated disease (CNS, bones, abdomen)

‐ Ex: Aspergillus species, mycobacterial, or Nocardia infections

• Superimposition of another process (lung injury or drug toxicity)

N Engl J Med. 1998;338(24):1741 ; http://www.uptodate.com/contents/pulmonary-infections-in-immunocompromised-patients?source=search_result&search=pneumonia+in+immunocompromised&selectedTitle=2%7E150

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So…• Vanc (at meningitic doses), cefotaxime, zosyn …to start

• ID consult

•Early imaging (CT / MRI) and specific microbiologic diagnoses are essential

•Invasive procedures (biopsies and bronchoscopy) are often necessary

•advanced diagnostic testing including immunohistology and quantitative molecular assays

•Reduction of immune suppression may be as important as antimicrobial therapy in the ultimate success of treatment

N Engl J Med. 1998;338(24):1741 ; http://www.uptodate.com/contents/pulmonary-infections-in-immunocompromised-patients?source=search_result&search=pneumonia+in+immunocompromised&selectedTitle=2%7E150

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‐ cystic fibrosis



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Simon RH. Cystic fibrosis: Antibiotic therapy for lung disease. UpToDatehttp://www.uptodate.com/contents/cystic-fibrosis-antibiotic-therapy-for-lung-disease?source=search_result&search=cystic+fibrosis+and+pneumonia&selectedTitle=1%7E150

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Cystic Fibrosis

• current culture recommendations‐perform cultures every three months

•although the value of antibiotic susceptibility testing based on conventional in vitro cultures has been questioned

‐the correlation between test results and clinical response is poor

Am J Infect Control. 2003;31(3 Suppl):S1.; J Pediatr. 2009;155(6 Suppl):S73.

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Cystic Fibrosis

The persistence of bacteria despite aggressive treatment is thought to be due to:

•Poor penetration of antibiotics into purulent airway secretions

•Native or acquired antibiotic resistance

•CF-related defects in mucosal defenses

•Biofilms produced by the bacteria that may render antibiotics ineffective or interfere with host defenses


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Clinical indicators to treat?• Increased cough

• Increased sputum production or chest congestion

• Decreased exercise tolerance or increased dyspnea with exertion

• Increased fatigue

• Decreased appetite

• Increased respiratory rate or dyspnea at rest

• Change in sputum appearance

• Fever (present in a minority of patients)

• Absenteeism from school or work

• Increased nasal congestion or drainage

J Pediatr. 2001;139(3):359.

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Treatment considerations

• Pseudomonas aeruginosa

‐Chronic infection - an independent risk factor for accelerated loss of pulmonary function and decreased survival

‐Conversion of P. aeruginosa to the mucoid phenotype worsens prognosis

• Burkholderia cepacia complex

‐Chronic infection - associated with an accelerated decline in pulmonary function and shortened survival in CF

‐Lung transplantation is associated with recurrent and often severe infection,

‐Lung transplantation associated with poor outcomes, particularly for those carrying B. cenocepacia

‐is considered to be a contraindication to transplantation in many centers

Pediatr Pulmonol. 2001;32(5):356; Pediatr Pulmonol. 2002;34(2):91; Paediatr Respir Rev. 2002;3(3):230; J Clin Microbiol. 2004;42(12):5537; Am J Respir Crit Care Med. 2006;173(4):421

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Treatment considerations•treat any S. aureus

•treat Achromobacter xylosoxidans

‐Some isolates can be particularly inflammatory and are associated with rates of FEV1 deterioration

•uncertainty regarding the importance of treating Stenotrophomonas maltophilia (S. maltophilia)

‐merely a marker of more severe lung disease or a cause of it?

•Aspergillus species are generally not treated

‐ appear to be an unlikely cause of pulmonary exacerbations


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• When in vitro testing can identify no antibiotic to which a bacterium is susceptible, select a combination of antibiotics that would otherwise be chosen empirically for that pathogen.

•generally avoid using two beta lactam antibiotics simultaneously

‐based upon in vitro studies showing the antimicrobial effect of adding the second beta lactam is unpredictable and can sometimes be antagonistic to the first

•continue administering oral azithromycin during the acute exacerbation if it is a component of the chronic pulmonary regimen.


Treatment considerations

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Antibiotic synergy testing

• The only large clinical trial that studied the effect of combination antibiotic susceptibility testing

‐failed to demonstrate any benefit associated with this approach

• Meta analysis: Combination antibiotic susceptibility testing

‐did not improve clinical or bacteriologic outcomes

‐did not prolong the period until the next acute exacerbation

Lancet. 2005;366(9484):463; Cochrane Database Syst Rev. 2008

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‐ cystic fibrosis



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Ventilator-dependent children• tracheostomy tubes bypass the protection of the nose, mouth, and upper airway

• the tube may result in various degrees of ulceration and tracheal denudation

• a humidified circuit results in colonization of the trachea

‐aspirates show an average of six isolates per specimen, and the mean bacterial concentration was 107 organisms / ml

• In 1976:

‐most frequent aerobic isolates - S. pneumoniae and S. aureus.

‐predominant anaerobes - gram-positive cocci, F. nucleatum, and B. fragilis.

‐replacement of one pathogen by another occurs frequently

• In 2010:

‐ gram-negative rods accounted for 71% of microorganisms

Ann Otol Rhinol Laryngol, 74 (1965), pp. 785–798; Chest, 85 (1984), pp. 39–44; Chest, 76 (1979), pp. 420–424 ; Chest, 74 (1978), pp. 635–639

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• Tracheitis v tracheobronchitis v pneumonia?

‐ colonization v real infection?

‐ culture material via tracheal aspirate suction trap, BAL, blind protected telescoping catheter (miniBAL)?

‐quantitative cultures, semi-quantitative?

•No correlation found between the concentrations of polymorphonuclear leukocytes and quantitative bacterial counts

Ventilator-dependent children

Chest, 74 (1978), pp. 635–639; CHEST 1979: 76: 420-424; CHEST 2013; 144(1):32–38; Pediatr Pulmonol. 2012; 47:409–414; Ped Crit Care Med. 2008 Jan;9(1):96-100;

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Ventilator-dependent children• following trach placement 40% readmitted within 12 months

‐45% pneumonia / tracheitis

•clinical indicators

‐oxygen saturations declined

‐secretions changed in color, viscosity, or odor

‐Increased need for airway suctioning

‐Increased need for oxygen supplementation or ventilatory support

‐new infiltrates or opacities on chest radiographs

•evidence-based guidelines lacking

‐treat based on prior cultures or current gram stain

Chest, 74 (1978), pp. 635–639; CHEST 1979: 76: 420-424; CHEST 2013; 144(1):32–38; Pediatr Pulmonol. 2012; 47:409–414; Ped Crit Care Med. 2008 Jan;9(1):96-100; Semin Pediatr Infect Dis 2006:17:11.

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‐ cystic fibrosis



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Ventilator Associated Pneumonia (VAP)

• The second most common hospital associated infection

• Accounts for 20% nosocomial infections in PICU’s

• Increased morbidity for patients

• Increased length of stay in the hospital

• Increased cost

•trach /vent dependent kids sig more likely to develop a VAT

CHEST 2013; 144(1):32–38

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VAP• clinical criteria for VAP are subjective and nonspecific:

‐worsening oxygenation

‐change in the quality or quantity of sputum production

‐new or progressive infiltrates

• from our AQI project - On 4 consecutive days, 4 different radiologists read the films and used 4 different words/phrases to describe the same thing

• autopsy series reveal that 1/3 to ½ of patients who met clinical criteria for VAP did not have pneumonia.

• CDC working group - shift the focus of surveillance from pneumonia alone to complications of mechanical ventilation in general.

The Joint Commission Journal on Quality and Patient Safety 2008: 34(11) 629.

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NEJM 2013:368;16

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VAC – new definitions

• do not include radiographic criteria

‐reflects the recognition that they are counterproductive in surveillance definitions

‐because they introduce substantial complexity and subjectivity without increasing accuracy

• opportunity to identify a population of patients who have serious complications that have previously not been acknowledged or attended to by quality-improvement programs

• will enable hospitals to benchmark their rates against peer institutions in a more meaningful way

• Antibiotic stewardship - the inclusion of an antibiotic criterion in the definition of IVAC will provide hospitals with a routine, widely reportable benchmark for the prescribing of antibiotics in their ICUs

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VAC in pediatrics• Of 645 mechanically ventilated patients admitted, 22 (3.4%) met criteria for VAC - incidence 0.829%, lower than the 2.3% to 11.5% reported in adult studies

•Patients with VAC experienced -

‐a significantly longer mean length of stay in the PICU (27.6 22.043 days vs 6.61 7.27 days; P 5 .000)

‐and higher mean total ventilator time (519.31 457.60 h vs 95.60 138.83 h; P 5 .000).

• significant association between tracheostomy and VAC ( P < .000) and between chronic ventilator dependence and VAC ( P < .002).

• cultured microorganisms: Gram-negative rods 71%; staphylococcal or streptococcal species 26%

‐Of those with two or more potentially causative pathogens - 67% (n=4) were in patients with a tracheostomy

CHEST 2013; 144(1):32–38

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Prevention

• bundled care!

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References: • Virkki R, Juven T, Rikalainen H, Svedström E, Mertsola J, Ruuskanen O. Differentiation of bacterial and viral pneumonia in children. Thorax.

2002;57(5):438.

• Tan TQ, Mason EO Jr, Barson WJ, Wald ER, Schutze GE, Bradley JS, Arditi M, Givner LB, Yogev R, Kim KS, Kaplan SL. Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae. Pediatrics. 1998;102(6):1369.

• Finnegan OC, Fowles SJ, White RJ. Radiographic appearances of mycoplasma pneumonia. Thorax. 1981;36(6):469.

• Korppi M, Kiekara O, Heiskanen-Kosma T, Soimakallio S. Comparison of radiological findings and microbial aetiology of childhood pneumonia. Acta Paediatr. 1993;82(4):360.

• Simpson W, Hacking PM, Court SD, Gardner PS. The radiological findings in respiratory syncytial virus infection in children. II. The correlation of radiological categories with clinical and virological findings. Pediatr Radiol. 1974;2(3):155.

• Dawson KP, Long A, Kennedy J, Mogridge N. The chest radiograph in acute bronchiolitis. J Paediatr Child Health. 1990;26(4):209.

• Bachur R, Perry H, Harper MB. Occult pneumonias: empiric chest radiographs in febrile children with leukocytosis. Ann Emerg Med. 1999;33(2):166.

• Margolis P, Gadomski A. The rational clinical examination. Does this infant have pneumonia? JAMA. 1998;279(4):308.

• Klompas M. Complications of Mechanical Ventilation — The CDC’s New Surveillance Paradigm. NEJM 2013:368;16

• Meyers, J., Shook, J., Pella, J., & Cron, S. G. Complete respiratory assessment score accurately predicts outcomes in children with acute reactive airway disease exacerbations [Abstract]. Academic Emergency Medicine, 1996: 3(5), 396.

• Rosenfeld M, Gibson RL, McNamara S, Emerson J, Burns JL, Castile R, Hiatt P, McCoy K, Wilson CB, Inglis A, Smith A, Martin TR, Ramsey BW. Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr Pulmonol. 2001;32(5):356.

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References cont• Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in

young children with cystic fibrosis. Pediatr Pulmonol. 2002;34(2):91.

• Speert DP. Advances in Burkholderia cepacia complex. Paediatr Respir Rev. 2002;3(3):230.

• Fauroux B, Hart N, Belfar S, BouléM, Tillous-Borde I, Bonnet D, Bingen E, Clément A. Burkholderia cepacia is associated with pulmonary hypertension and increased mortality among cystic fibrosis patients. J Clin Microbiol. 2004;42(12):5537.

• Kalish LA, Waltz DA, Dovey M, Potter-Bynoe G, McAdam AJ, Lipuma JJ, Gerard C, Goldmann D. Impact of Burkholderia dolosa on lung function and survival in cystic fibrosis. Am J Respir Crit Care Med. 2006;173(4):421.

• Rosenfeld M, Emerson J, Williams-Warren J, Pepe M, Smith A, Montgomery AB, Ramsey B. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr. 2001;139(3):359.

• Aaron SD, Vandemheen KL, Ferris W, Fergusson D, Tullis E, Haase D, Berthiaume Y, Brown N, Wilcox P, Yozghatlian V, Bye P, Bell S, Chan F, Rose B, Jeanneret A, Stephenson A, Noseworthy M, Freitag A, Paterson N, Doucette S, Harbour C, Ruel M, MacDonald N. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. Lancet. 2005;366(9484):463.

• Waters V, Ratjen F. Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis. Cochrane Database Syst Rev. 2008

• Simon RH. Cystic fibrosis: Antibiotic therapy for lung disease. UpToDate (found at: http://www.uptodate.com/contents/cystic-fibrosis-antibiotic-therapy-for-lung-disease?source=search_result&search=cystic+fibrosis+and+pneumonia&selectedTitle=1%7E150)

• Saiman L, Siegel J, Cystic Fibrosis Foundation Consensus Conference on Infection Control Participants. Infection control recommendations for patients with cystic fibrosis: Microbiology, important pathogens, and infection control practices to prevent patient-to-patient transmission. Am J Infect Control. 2003;31(3 Suppl):S1.

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References con’t • Cystic Fibrosis Foundation, Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, Michel SH, Parad RB, White TB, Farrell

PM, Marshall BC, Accurso FJ. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr. 2009;155(6 Suppl):S73.

• Brook I. Bacterial Colonization, Tracheobronchitis, and Pneumonia following Tracheostomy and Long-Term Intubation in Pediatric Patients. CHEST 1979: 76: 420-424

• Simpson VS, Bailey A, Higgerson RA and Christie L M. Ventilator-Associated Tracheobronchitis in a Mixed Medical/Surgical Pediatric ICU. CHEST 2013; 144(1):32–38

• Nseir S, Di Pompeo C, Soubrier S, et al . Effect of ventilatorassociated tracheobronchitis on outcome in patients without chronic respiratory failure: a case-control study . Crit Care 2005 ; 9 ( 3 ): R238 - R245 .

• Agrafi otis M Siempos II, Falagas ME . Frequency, prevention, outcome and treatment of ventilator-associated tracheobronchitis: systematic review and meta-analysis . Respir Med . 2010 ; 104 ( 3 ): 325 - 336 .

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• Kun SS, Edwards JD, Davidson Ward SL, Keens TG. Hospital Readmissions for Newly Discharged Pediatric Home Mechanical Ventilation Patients. Pediatr Pulmonol. 2012; 47:409–414.

• Graf JM, Montagnino BA, Hueckel R, McPherson ML. Pediatric tracheostomies: a recent experience from one academic center. Ped Crit Care Med. 2008 Jan;9(1):96-100.

• Fishman JA. Pulmonary infections in immunocompromised patients. Found at: http://www.uptodate.com/contents/pulmonary-infections-in-immunocompromised-patients?source=search_result&search=pneumonia+in+immunocompromised&selectedTitle=2%7E150

• Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med. 1998;338(24):1741.

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• Bradley, J. S., Byington, C. L., Shah, S. S., Alverson, B., Carter, E. R., Harrison, C., et al.. The management of communityacquired pneumonia in infants and children older than 3 months of age: Clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clinical Infectious Diseases 2011: 53(7), e25-e76.

• Michelow, I. C., Olsen, K., Lozano, J., Rollins, N. K., Duffy, L. B., Ziegler, T., et al. (2004). Epidemiology and clinical characteristics of communityacquired pneumonia in hospitalized children. Pediatrics, 2004:113(4), 701-707.

• S.A. Friedberg, T.E. Griffith, G.M. Hass. Histologic changes in the trachea following tracheostomy. Ann Otol Rhinol Laryngol, 74 (1965), pp. 785–798

• M.S. Niederman, R.D. Ferranti, A. Zeigler et al. Respiratory infection complicating long term tracheostomy. The implication of persistent gram-negative tracheobronchial colonization. Chest, 85 (1984), pp. 39–44

• J.G. Barlett, L.G. Faling, S. Willey. Quantitative Tracheal bacteriologic and cytologic studies in patients with long term tracheostomies. Chest, 74 (1978), pp. 635–639

• Graf J, Stein F. Tracheitis in pediatric patients. Semin Pediatr Infect Dis 2006:17:11.

• Brilli RJ, Sparling KW, Lake MR, Butcher J, Myers, SS, Clark MD, Helpling A, Stutler ME.The Business Case for Preventing Ventilator-Associated Pneumonia in Pediatric Intensive Care Unit Patients. The Joint Commission Journal on Quality and Patient Safety 2008: 34(11) 629.

pneumonia in the critical care setting laura loftis, m.d., m.s. associate professor of pediatrics...

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