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Current Diagnosis & Treatment of Community-Acquired Pneumonia

in Children

Highlights of the PIDS/IDSA National Guidelines

Samir S. Shah, MD, MSCE, FAAP Professor, Department of Pediatrics University of Cincinnati College of Medicine Director, Division of Hospital Medicine Cincinnati Children's Hospital Medical Center

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Prepared for your next patient.

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Disclaimers Statements and opinions expressed are those of the authors and not

necessarily those of the American Academy of Pediatrics.

Mead Johnson sponsors programs such as this to give healthcare professionals access to scientific and educational information provided by experts. The presenter has complete and independent control over the planning and content of the presentation, and is not receiving any compensation from Mead Johnson for this presentation. The presenter’s comments and opinions are not necessarily those of Mead Johnson. In the event that the presentation contains statements about uses of drugs that are not within the drugs' approved indications, Mead Johnson does not promote the use of any drug for indications outside the FDA-approved product label.

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Disclaimers continued I have no financial conflicts of interest to disclose. I have not received any compensation for preparing and presenting

this webinar. I served as Associate Chair of the Pediatric Infectious Diseases

Society/Infectious Diseases Society of America Pneumonia Guidelines Committee, the topic of this presentation.

Sources of current research support:o National Institute of Allergy and Infectious Diseaseso Agency for Healthcare Research and Qualityo Children’s Hospitals Associationo Robert Wood Johnson Foundation

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Objectives Discuss the rationale for creating pediatric

community-acquired pneumonia (CAP) national guidelines.

Describe currently recommended diagnostic and treatment strategies for CAP in the United States.

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Why Do We Need Guidelines? Role of guidelines

o Assist in healthcare decision-makingo Reduce variation in clinical practiceo Lead to better patient care and outcomes

Only as good as the evidence on which they are based

Most useful for conditions with substantial variation in clinical practice and outcomes

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Context for the US Guidelines CAP is the most common serious childhood infection

in the US.o 3 million outpatient visits each yearo >150,000 hospitalizations each yearo Up to 15% of children hospitalized with CAP have a serious

pneumonia-associated complication such as empyema. In the US, there is substantial variation across

hospitals and physicians in diagnosis, treatment, and outcomes.

Kronman MP. Pediatrics. 2011; Shah SS. J Hosp Med. 2011; Lee GE. Pediatrics. 2010; Shah SS. Pediatr Pulmonol. 2010

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Diagnostic Testing for CAP at 43 US Hospitals

Brogan TV. Pediatr Infect Dis J. 2012

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Diagnostic Testing for CAP at 43 US Hospitals

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Diagnostic Testing for CAP at 43 US Hospitals

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Treatment for CAP at 43 US Hospitals

Data from Ambroggio LV, et al. Pediatr Infect Dis J. 2012

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Available Free Online and In Print Guidelines available at: www.idsociety.org

Bradley JS, Byington CL, Shah SS, and Alverson B, Carter ER, Harrison C, Kaplan SL, Mace S, McCracken G, Moore M, St. Peter S, Stockwell J, Swanson JT. The management of community-acquired 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. Clin Infect Dis. 2011;53:e25–e76

Bradley JS, Byington CL, Shah SS, and Alverson B, Carter ER, Harrison C, Kaplan SL, Mace S, McCracken G, Moore M, St. Peter S, Stockwell J, Swanson JT. Executive Summary: The management of community-acquired 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. Clin Infect Dis. 2011;53:617–630

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Consensus Development Based on Evidence 92 recommendations Consensus development based on evidence

o GRADE working group (Grading of Recommendations, Assessment, Development, and Evaluation)

o Method of assigning strength of recommendation and quality of evidence to each recommendation

Strength of Recommendation (Strong or Weak)

Quality of Evidence (High, Moderate, or Low)

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Evidence-Based Guidelines Clinical Recommendations

o Site of careo Diagnostic testingo Anti-infective treatmento Adjunctive treatmento Management of the child not responding to treatmento Discharge criteriao Prevention

Future research

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Evidence-Based Guidelines Clinical Recommendations

o Site of careo Diagnostic testingo Anti-infective treatmento Adjunctive treatmento Management of the child not responding to treatmento Discharge criteriao Prevention

Future research

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Outline Diagnostic Testing

o Pulse oximetryo Chest x-rayo Blood cultureo Atypical bacteria testingo Viral testingo Complete blood counts

Anti-Infective Treatment

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Definition of CAP CAP is the presence of signs and symptoms of

pneumonia in a previously healthy child due to an infection acquired outside of the hospital.

Guideline scopeo Age 3 months – 18 yearso Exclusionary conditions

• Immune deficiency• Chronic lung disease (e.g., cystic fibrosis)• Mechanical ventilation

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Diagnostic Testing—Pulse Oximetry Outpatient and InpatientRecommendation RecommendedComments

In all children with pneumonia and suspected hypoxemia.

The presence of hypoxemia should guide decisions and further diagnostic testing.

Recommendation Strength Strong

Evidence Quality Moderate

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Initial Chest X-Ray—Recommendation Outpatient InpatientRecommendation NOT Recommended Recommended RecommendedComments

For confirmation of suspected CAP in

patient well enough to be treated in

outpatient setting (after evaluation in office, clinic, or ED).

Patients with hypoxemia, significant

respiratory distress, and failed antibiotic

therapy; to verify presence or absence

of complications.

All patients hospitalized with CAP;

to document presence, size, and character of infiltrates and identify

complications that may require interventions.

Strength Strong Strong Strong

Evidence Quality High Moderate Moderate

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Initial Chest X-Ray—Rationale Chest x-rays (CXRs) not routinely required for outpatient CAP CXRs:

o Do not reliably distinguish bacterial from viral CAP or among the various bacterial pathogens

o Impractical in office setting• Often requires travel to a separate facility• Barriers to physicians obtaining timely results

o CXR in outpatient setting infrequently changes clinical management

Guideline provides guidance on when to perform CXR in outpatient setting

Swingler GH. Cochrane Database Syst Rev. 2008; Swingler GH. Lancet. 1998; Novack V. J Intern Med. 2006; Alario AJ. J Pediatr. 1987; Grossman LK. Ann Emerg Med. 1988

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Repeat Chest X-Ray—Recommendation

Outpatient AND InpatientRecommendation NOT RecommendedComments

Not routinely indicated in children who recover uneventfully

Recommendation Strength Strong

Evidence Quality Moderate

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Repeat Chest X-Ray—Recommendation Outpatient AND InpatientRecommendation Recommended Recommended RecommendedComments

For inadequate clinical improvement,

progressive symptoms, or clinical deterioration within

48–72 hours after initiation of antibiotics

In children with complicated

pneumonia with worsening

respiratory distress or clinical instability

4–6 weeks after the diagnosis of CAP in

limited circumstances (e.g., recurrent

pneumonia in same lobe or suspicion of an

anatomic anomaly)

Recommendation Strength Strong Strong Strong

Evidence Quality Moderate Low Moderate

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Repeat Chest X-Ray—Rationale Repeat CXRs commonly identify persistent or residual

abnormalities 3–6 weeks later. o Abnormalities rarely alter management.o Abnormalities do not predict treatment failure or worse

clinical outcome. Repeat CXRs represent unnecessary radiation

exposure to infants and children.

Gibson NA. BMJ. 1993; Virkki R. Pediatr Pulmonol. 2005; Grossman LK. Pediatrics. 1979; Wacogne I. Arch Dis Child. 2003; Heaton P. N Z Med J. 1998; Bruns AH. Clin Infect Dis. 2007

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Blood Cultures―Recommendations Outpatient InpatientRecommendation NOT Recommended Recommended RecommendedComments

Non-toxic, fully immunized children treated as

outpatients

Failure to demonstrate clinical improvement,

progressive symptoms, or deterioration after initiation of antibiotic

therapy

Requiring hospitalization for moderate-severe

bacterial CAP

Strength Strong Strong Strong

Evidence Quality Moderate Moderate Low

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Blood Cultures—Rationale Outpatient

o Infrequently identifies pathogens (<2%)o False-positives more common than true positives at some

hospitalso Rarely informs outpatient management

Bonadio WA. Pediatr Emerg Care. 1988; Hickey RW. Ann Emerg Med. 1996; Shah SS. Arch Pediatr Adolesc Med. 2003; Shah SS. Pediatr Infect Dis J. 2011

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Blood Cultures—Rationale Outpatient

o Infrequently identifies pathogens (<2%)o False-positives more common than true positives at some

hospitalso Rarely informs outpatient management

Inpatiento Positive in ~3% of uncomplicated pneumoniao Positive in ~15% with empyemao Allows for culture-directed therapy when positiveo Provides local epidemiologic data

Bonadio WA. Pediatr Emerg Care. 1988; Hickey RW. Ann Emerg Med. 1996; Shah SS. Arch Pediatr Adolesc Med. 2003; Shah SS. Pediatr Infect Dis J. 2011

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Atypical Bacteria Testing―Recommendation

Mycoplasmapneumoniae

Chlamydophila pneumoniae

Recommendation Recommended NOT recommendedComments

If signs/symptoms consistent with but not classic for Mycoplasma; can help guide antibiotic

selection.

Reliable and readily available diagnostic tests

do not currently exist.

Strength Weak Strong

Evidence Quality Moderate High

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Atypical Bacteria Testing―Rationale Evolving understanding of M. pneumoniae

epidemiologyo Increasingly identified in younger children

Rapid tests (IgM and PCR) availableo Variable test accuracyo Treatment is not mandatory, especially with low likelihood

of infection (e.g., negative test), as benefit of macrolide antibiotics uncertain

Heiskanen-Kosma T. Pediatr Infect Dis J. 1998; Michelow IC. Pediatrics. 2004; Korppi M. Respirology. 2004; Thurman KA. Clin Infect Dis. 2009

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Viral Testing―Recommendations

Influenza Other Respiratory VirusesRecommendation Recommended RecommendedComments

Use sensitive and specific tests.Positive influenza test may

decrease the need for additional tests and antibiotic use, while

guiding the use of antiviral agents in both outpatient and inpatient

settings.

Can modify clinical decision making in children with suspected

pneumonia; antibiotics are not required in the absence of

findings that suggest bacterialco-infection.

Strength Strong Weak

Evidence Quality High Low

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Diagnostic Testing—Viral Pathogens Antibacterial therapy is not necessary in children,

either outpatients or inpatients, with a positive test for influenza virus in the absence of clinical, laboratory, or radiographic findings that suggest bacterial co-infection.

Strong recommendation; High-quality evidence

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Viral Testing—Rationale Influenza testing

o Positive tests reduce antibiotic use and ancillary testing (e.g., CXR, CBC) by >50%.

o Positive tests guide antiviral treatment decisions.• Early treatment improves outcomes.

Bonner AB. Pediatrics. 2003; Esposito S. Arch Dis Child. 2003; Iyer SB. Acad Emerg Med. 2006; Benito-Fernandez J. Pediatr Infect Dis J. 2006

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Viral Testing—Recommendations

Influenza Other Respiratory VirusesRecommendation Recommended RecommendedComments Use sensitive and specific tests.

Positive influenza test may decrease the need for additional

tests and antibiotic use, while guiding the use of antiviral

agents in both outpatient and inpatient settings.

Can modify clinical decision making in children with suspected

pneumonia; antibiotics are not required in the absence of

findings that suggest bacterialco-infection.

Strength Strong Weak

Evidence Quality High Low

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Complete Blood Count—Recommendation Outpatient InpatientRecommendation NOT Recommended NOT RecommendedComments

However, may provide useful information in those with more

serious disease for clinical management in the context of

clinical exam and other laboratory and imaging studies.

However, may provide useful information for those with severe pneumonia; to be interpreted in the context of clinical exam and

other laboratory and imaging studies.

Strength Weak Weak

Evidence Quality Low Low

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Complete Blood Count—Rationale Anemia and thrombocytopenia may suggest

hemolytic-uremic syndrome.o Rarely an occult process.

WBC count has poor specificity for diagnosis of bacterial pneumonia.o WBC elevated in many children with CAP.o Most children with elevated WBC do not have CAP.o WBC does not reliably distinguish bacterial from viral CAP.

Waters AM. J Pediatr. 2007; Banerjee R. Pediatr Infect Dis J. 2011; Korppi M. Eur Respir J. 1997

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Antibiotic Choice—Outpatient Age of Child Infant / Preschool-Age School-AgeRecommendation No antibiotics Amoxicillin Amoxicillin AzithromycinComments Antibiotics NOT

routinely required

because viral pathogens are

most prevalent.

First-line therapy if previously

healthy and immunized.

Provides excellent

coverage for S. pneumoniae.

First-line therapy if previously

healthy and immunized.

Consider atypical bacterial

pathogens.

For treatment of older children

with findings compatible

with CAP caused by atypical

pathogens.

Strength Strong Strong Strong Weak

Evidence Quality High Moderate Moderate Moderate

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Antibiotic Choice—Outpatient Alternatives

Allergy Amoxicillin AzithromycinAlternatives

• 2nd/3rd generation Cephalosporin• Clindamycin• Levofloxacin

•Doxycycline (>7 years old)•Levofloxacin or Moxifloxacin

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Antibiotic Choice—Inpatient First Line Second LineRecommendation Ampicillin / PCN G 3rd Generation CephalosporinComments

Immunized infant, preschool, or school-age child.

Non-immunized, in regions with high levels of PCN

resistant pneumococcal strains, or in children with life-threatening infection.

Non-beta lactam agents (e.g., vancomycin) are not needed

for the treatment of pneumococcal pneumonia.

Strength Strong Weak

Evidence Quality Moderate Weak

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Antibiotic Choice—Inpatient Secondary Agents Atypical Bacteria S. aureusRecommendation Macrolide Vancomycin or Clindamycin Comments

In addition to beta-lactam therapy if atypical bacteria

are significant considerations. Instead of beta-lactam if findings are characteristic of atypical

infection.

In addition to beta-lactam therapy if clinical,

laboratory, or imaging characteristics are

consistent with infection caused by S. aureus.

Recommendation Strength Weak Strong

Evidence Quality Moderate Low

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Antibiotic Choice—Rationale S. pneumoniae remains most common bacterial cause of CAP Decreasing S. pneumoniae antibiotic resistance

o >50% decrease in penicillin-non-susceptible infectionso >50% decrease strains in resistance to multiple antibiotics

Kyaw MH. N Engl J Med. 2006

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Antibiotic Choice—Rationale Penicillin resistance is not associated with treatment

failure for non-CNS S. pneumoniae infections.o In vitro, bactericidal activity achieved at low concentrations

relative to MICo In vivo, high and sustained concentrations achieved in

serum and lung• Amoxicillin administered at 80 mg/kg/day• Ampicillin administered at 300 mg/kg/day

Yu VL. Clin Infect Dis. 2003; Perez-Trallero E. J Antimicrob Chemother. 1998; Perez-Trallero E. J Chemother. 2001

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Antibiotic Choice—Rationale Macrolide resistance and 2nd generation cephalosporin

resistance are associated with treatment failure for non-CNS S. pneumoniae infections.

Vancomycino Not necessary for S. pneumoniaeo MRSA less common and rarely “occult”o Challenges

Poor lung penetration compared with aminopenicillins Associated with nephrotoxicity May require monitoring trough concentrations or continuous infusion

Yu VL. Clin Infect Dis. 2003; Perez-Trallero E. J Antimicrob Chemother. 1998; Chung J. Anaesth Intensive Care. 2011

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Minimizing Resistance―Duration of Therapy Treatment for the shortest effective duration will minimize exposure of both pathogens and normal microbiota, and minimize the selection for resistance.

Strong recommendation; Low-quality evidence

Treatment courses of 10 days have been best studied. Shorter courses may be just as effective, particularly for more mild disease managed on an outpatient basis.

Strong recommendation; Moderate-quality evidence

Infections caused by certain pathogens, notably CA-MRSA, may require longer treatment than those caused by S. pneumoniae.

Strong recommendation; Moderate-quality evidence

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Final Thoughts

Guidelines are only as good as the evidence on which they are based.

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Final Thoughts

Developing guidelines is relatively easycompared to implementing them.

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Outpatient Bottom LineTest Should I do it? Comment

Pulse oximetry YesCXR No Consider in some circumstancesRepeat CXR No Consider in some circumstancesInfluenza testing Yes During influenza seasonMycoplasma Yes Encouraged if considering macrolideSputum NoBlood culture No Yes, if deterioration or no improvementCBC No

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Outpatient Bottom Line

Role Antibiotic CommentFirst-Line Amoxicillin

Alternate 2nd/3rd generation cephalosporin; clindamycin; levofloxacin

Alternate Macrolide Add to include coverage for atypicals.

Alternate Macrolide Substitute to include coverage for atypicals if pneumococcal coverage is not desired.

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Inpatient Bottom LineTest Should I do it? Comment

Pulse oximetry YesCXR YesRepeat CXR No Consider in some circumstancesInfluenza testing Yes During influenza seasonMycoplasma Yes Encouraged if considering macrolideSputum Yes If child can provideBlood culture YesCBC No

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Inpatient Bottom LineRole Antibiotic CommentFirst-Line Ampicillin

Alternate Cefotaxime or Ceftriaxone If unimmunized

Alternate Macrolide Add to include coverage for atypicals.

Alternate Macrolide Substitute to include coverage for atypicals if pneumococcal coverage is not desired.

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