UNC Children’s & Carolina Antimicrobial Stewardship Program
JOINT GUIDELINE
Assessment and Management of Hospital-Acquired and Ventilator-
Associated Pneumonia in Children
Guideline Development Team: Zach Willis, MD, MPH; Bill Wilson, PharmD, BCPS; Lauren Walter, PharmD;
Shawna Beck, PharmD; Will Stoudemire, MD; Jen Fuchs, MD; Jenny Boyd, MD
INTRODUCTION
Hospital-acquired pneumonia (HAP) and Ventilator-associated pneumonia (VAP) are healthcare-acquired
conditions with significant risk of morbidity and mortality. Hospitalized patients may have multiple risk factors
for pneumonia, such as recumbent position, impaired cough reflex, procedural sedation, immunocompromised
status, and/or artificial airways. Prompt recognition of pneumonia in hospitalized patients can prevent serious
complications. However, cultures of respiratory secretions are difficult to obtain in patients without an artificial
airway or have limited specificity in patients with an endotracheal tube or tracheostomy tube.
This guideline document will address the diagnosis and treatment of HAP and VAP in pediatric patients at UNC
Children’s. Guidelines for HAP and VAP prevention are maintained separately.
Inclusion Criteria
• Current admission at UNC Children’s other than Newborn Critical Care Center
• Age ≤21 years
• Hospitalized (including at other hospitals) >48 hours at the time of evaluation
Exclusion Criteria
• Patients outside the PICU with a tracheostomy
DIAGNOSIS OF HAP AND VAP
Definition of HAP and VAP
HAP is pneumonia that develops at least 48 hours after hospital admission. VAP is HAP that develops at least
48 hours following endotracheal intubation.
When to suspect HAP
Patient with new lung infiltrate PLUS clinical evidence that infiltrate is infectious, with at least one of:
• New onset of fever
• Purulent (may be unusually thick, colors other than white/tan) and/or significantly increased sputum
• Leukocytosis or leukopenia (new)
• Increasing FiO2/supplemental oxygen requirement
When to suspect VAP
Patient meeting HAP criteria after >48 hours of endotracheal intubation.
Tracheitis and Tracheobronchitis
Potentially pathogenic bacteria frequently colonize respiratory devices. Occasionally they may cause infection
of proximal airways without frank pneumonia – the absence of alveolar infiltrates and usually the absence of a
new oxygenation defect.
Note: Consider respiratory viral infections in the differential diagnosis of suspected HAP/VAP.
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FIGURE 1. Diagnostic algorithm for VAP and HAP.
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EMPIRIC ANTIBIOTIC SELECTION FOR SUSPECTED HAP AND VAP
Overview of Antibiotic Selection FIGURE 2. Antibiotic selection for suspected
Review prior cultures; strongly consider coverage HAP or VAP
of any pathogens isolated from respiratory cultures
during current or recent admissions.
Most patients should receive cefepime alone, but
there are many exceptions as listed below.
Cefepime has good activity against Gram-negative
and most Gram-positive pathogens (excluding
MRSA), including many oral anaerobes.
Severe Beta-Lactam Allergy
Includes any of the following (consult ID or ASP if
uncertain):
• Urticaria or anaphylaxis (IgE-mediated)
• Angioedema
• Respiratory or cardiovascular compromise
Stevens-Johnson syndrome or Toxic Epidermal
Necrolysis (TEN)
• DRESS syndrome (Drug Reaction with
Eosinophilia and Systemic Symptoms)
• Acute Generalized Exanthematous Pustulosis
(AGEP)
Indications for vancomycin
• Sepsis/septic shock (follow Code Sepsis
protocols)
• History of MRSA colonization or infection in the
last 2 years
• Necrotizing pneumonia
• Use of aztreonam (limited Gram-positive
coverage)
• Significant immune compromise
Alternatives to vancomycin in patients with
renal impairment or true allergy
• Linezolid - usually preferred, monitor for drug-
drug interactions
• Trimethoprim-sulfamethoxazole
• Ceftaroline - only if contraindications to above
(requires ID or ASP approval)
• Clindamycin recommended only when isolate is
known to be susceptible
Dedicated Anaerobic Coverage
Rarely necessary in VAP. Cefepime has good
coverage of oral anaerobes. Exceptions include:
very high risk of aspiration due to underlying
neurologic conditions, witnessed aspiration
preceding pneumonia, poor dentition. Anaerobic coverage is also warranted for lung abscesses.
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Expanded Gram-negative coverage
Generally indicated only when patients have known prior cefepime-resistant infections OR if patient is
worsening on empiric coverage. In most cases, the recommended approach is to use meropenem OR add an
aminoglycoside.
Prior colonization with multi-drug resistant organisms
Many patients with suspected VAP/VAT have had recent positive respiratory cultures (within the prior 90 days).
Empiric coverage of recently identified organisms is usually reasonable, especially in patients with a
tracheostomy or who have remained intubated since the prior culture. When a new infection is suspected,
coverage should not be limited to prior organisms. Certain organisms, such as Acinetobacter,
Stenotrophomonas, Achromobacter, etc., have idiosyncratic susceptibility patterns. Prior susceptibilities should
be reviewed and may change empiric antibiotic coverage.
Aerosolized Antibiotics
Rarely recommended. Occasional exceptions may be made for highly drug-resistant organisms.
TABLE 1. Antibiotic selection for suspected HAP/VAP in common scenarios.
Scenario Empiric Regimen
Most cases Cefepime alone
Sepsis or septic shock Vancomycin plus cefepime
Severe allergy to penicillins and Vancomycin plus aztreonam
cephalosporins
MRSA colonization or prior MRSA infection Vancomycin plus cefepime
Anaerobic coverage needed Piperacillin-tazobactam OR cefepime plus metronidazole.
Do not add vancomycin to piperacillin-tazobactam
Recent infection with multi-drug resistant Use prior susceptibilities as appropriate. Consider ID
organism (MDRO) within prior 30-60 days consultation. Generally do not use a narrower-spectrum
regimen than otherwise recommended for the scenario.
• ESBL producer: meropenem
• Carbapenem-resistant: consult ID
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DEFINITIVE TREATMENT OF HAP AND VAP
Determining if the patient truly has pneumonia
Definitions of HAP and VAP require a positive respiratory culture for definitive diagnosis (not always possible in
HAP). Respiratory cultures have poor specificity, and positive results often represent colonization of an airway
device or respiratory tract epithelium. Consider the following factors in assessing whether the patient has
pneumonia.
TABLE 2. Clinical factors that are more or less suggestive of pneumonia.
Pneumonia Less Likely Pneumonia More Likely
Recent positive culture for same organism Absence of prior positive culture for colonizing organism
Gram stain with >25 PMNs/LPF Gram stain with 2+ PMNs or greater
Gram stain without organisms (usually rejected by Gram stain with 2+ or greater organisms
lab; it is rarely helpful to request culture)
Light growth of organisms on culture Moderate or heavy (2+ or greater) growth of organisms
Culture obtained from tracheal aspirate or ETT Culture obtained by sputum or bronchoalveolar lavage
aspirate (BAL)
Low pre-test probability (low suspicion for High pre-test probability (syndrome highly consistent
pneumonia when cultures sent) with pneumonia)
Adjusting empiric therapy in response to species identification
In most cases, the species will be known before susceptibilities are available. Antibiotics may need to be
adjusted depending on the identification. This table is meant to address the most common and clinically
significant results.
TABLE 3. Targeting therapy before and after susceptibilities are available
Organism Before Susceptibilities After Susceptibilities
Staphylococcus Vancomycin (preferred) or linezolid. If patient MSSA: nafcillin or cefazolin
aureus is doing well on cefepime alone, it may not be MRSA: vancomycin or linezolid
necessary to add vancomycin.
Pseudomonas Continue empiric antipseudomonal beta- Use most targeted therapy possible.
aeruginosa lactam (most often cefepime). If patient is
declining, consider addition of IV tobramycin.
Gram-negative Most are susceptible to 3rd and 4th generation Most targeted therapy possible.
enterics (E. coli, K. cephalosporins and piperacillin-tazobactam. Ampicillin, ampicillin-sulbactam, and
pneumoniae, etc) cefazolin are all acceptable if
organism is susceptible.
Potential AmpC Cefepime is preferred. Cefepime or meropenem. Other
producers Very severe illness: meropenem cephalosporins and pip-tazo should
(Enterobacter, usually not be used.
Citrobacter, Serratia)
Acinetobacter Consult ID. Meropenem and ampicillin- Use most targeted therapy possible.
baumanii sulbactam are most likely to be active. If Often this is ampicillin-sulbactam.
patient is declining, consider addition of Cefepime, ceftazidime, and
levofloxacin or IV amikacin. meropenem are often used.
Stenotrophomonas Trimethoprim-sulfamethoxazole is preferred. TMP-SMX if active. Levofloxacin is
maltophilia When contraindicated, levofloxacin or second-line, then minocycline.
minocycline are options.
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Duration of treatment for nosocomial respiratory infections
The generally accepted duration for HAP and VAP is 7 days. Note that these may need to be extended when
purulent complications develop, such as necrotizing pneumonia or empyema.
Treatment of ventilator-associated tracheobronchitis is controversial, but some experts believe it is warranted
as treatment may decrease the risk of later VAP and decrease time on ventilator. When treating this condition,
the maximum recommended duration is 5 days.
TABLE 4. Duration of Therapy for HAP, VAP, and VAT
Diagnosis Definition Duration Comment
HAP or VAP Systemic signs of infection plus 7 days May be complicated by necrotizing
pulmonary infiltrate plus increased pneumonia or pleural empyema. In
sputum and/or increased these cases, longer durations are
ventilatory/oxygen needs warranted. Consult ID.
Ventilator- Systemic signs of infection plus 0-5 days Treatment may reduce risk of later VAP
associated purulent sputum and positive and may reduce time to extubation. If
tracheobronchitis culture without pneumonia on treatment, no more than 3-5 days.
CXR
Dosing recommendations for commonly used antibiotics
TABLE 5: Antibiotic Dosing Recommendations for Patients >1 Month of Age without Renal Dysfunction
Antibiotic Dosing Information Max Dose Renal Adjustment Needed?
Aztreonam 40 mg/kg/dose IV q8h 2000mg YES
Cefepime 50 mg/kg/dose IV q8h 2000mg YES
Ceftaroline <2 yo: 8 mg/kg/dose IV q8h 600mg YES
2-<18 yo & ≤33kg: 12 mg/kg/dose IV q8h
≥2 yo & >33kg: 600 mg IV q12h
Clindamycin 13 mg/kg/dose IV/PO q8h 600mg NO
Linezolid <12 yo: 10 mg/kg/dose IV/PO q8h 600mg YES (only HD/PD)
≥12 yo: 600mg IV/PO q12h
Meropenem 20 mg/kg/dose IV q8h 1000mg YES
Metronidazole 10 mg/kg/dose IV/PO q8h 500mg NO
Piperacillin/ <9 mo: 80 mg piperacillin/kg/dose IV q6h 4000mg YES
tazobactam ≥9 mo: 100 mg piperacillin/kg/dose IV piperacillin
q6h
Trimethoprim/ 5 mg TMP/kg/dose IV/PO q8h 320mg TMP YES
sulfamethoxazole
Vancomycin Dose per pharmacy 2000mg YES
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REFERENCES
1. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and
Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society
of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111.
doi:10.1093/cid/ciw353
2. Kenaa B, Richert ME, Claeys KC, et al. Ventilator-Associated Pneumonia: Diagnostic Test
Stewardship and Relevance of Culturing Practices. Curr Infect Dis Rep. 2019;21(12):50.
doi:10.1007/s11908-019-0708-3
3. Dassner AM, Nicolau DP, Girotto JE. Management of Pneumonia in the Pediatric Critical Care Unit:
An Area for Antimicrobial Stewardship. Curr Pediatr Rev. Published online December 4, 2016.
4. Fischer JE, Ramser M, Fanconi S. Use of antibiotics in pediatric intensive care and potential savings.
Intensive Care Med. 2000;26(7):959-966. doi:10.1007/s001340051288
5. Willson DF, Conaway M, Kelly R, Hendley JO. The lack of specificity of tracheal aspirates in the
diagnosis of pulmonary infection in intubated children. Pediatr Crit Care Med. 2014;15(4):299-305.
doi:10.1097/PCC.0000000000000106
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