Clinical Pathways Community Acquired Pneumonia (CAP)•EPIC (Etiology of Pneumonia in the Community)...

Clinical Pathways

Community Acquired Pneumonia (CAP)

Jennifer Girotto, Pharm D

Grace Hong, APRN

Anand Sekaran, MD

An evidence-based guideline that decreases unnecessary variation and helps promote safe, effective, and consistent patient care.

What is a Clinical Pathway?

• Decrease variation in antibiotic usage for CAP

• Decrease unnecessary use of broad spectrum antibioticso Utilization of procalcitonin, MRSA nasal PCR

• Decrease unnecessary use of azithromycin

• Optimize ampicillin/amoxicillin dosing for local pneumococcal resistance

• Decrease antibiotic usage to shortest effective duration

• Increase appropriate use of Oseltamivir

Objectives of Pathway

• Infectious Disease Society of America published guidelines for CAP in 20111

o CXR required to support the diagnosis

o Strongly encouraged testing if the result was likely to change individual antibiotic management

o Blood cultures for those that were very ill

o Modify antibiotic recommendations based on local susceptibility patterns

o Treatment duration of a minimum of 5 days, afebrile 48-72 hours and no more than 1 clinical instability sign before discontinuing antibiotics

• EPIC (Etiology of Pneumonia in the Community) Study: a prospective, multi-center, population-based, active surveillance study from Jan 1 2010-June 30, 2012• 3 pediatric hospitals, 5 adult hospitals

• Assessed the burden of pneumonia hospitalizations in children and adults in the U.S.

• Identify viral and bacterial etiologies

• Have conducted numerous studies on the burden of CAP

Background

• Viral pneumonia was the most common cause of pneumonia among children hospitalized for CAP2,3

• Increased rates of anti-MRSA treatment despite low prevalence of MRSA PNA4

BackgroundEPIC Study - Publications

• Removal of prematurity as an exclusion criteria

• Utilization of procalcitonin and its role in antibiotic usage

• Utilization of MRSA nasal swab and indications for Vancomycin use

• Azithromycin usage and second-sign restrictions

• Duration of antibiotics:o Mild/Moderate – 7 days

o Severe - 14 days (but use procalcitonin to help determine duration)

• Clarified discharge antibiotics

Updates for 2019: What has changed in this Pathway?

• Precursor of calcitonin, and a cytokine mediator

• Elevated in bacterial infections (not viral)

• Studies have shown that PCT can be better at determining bacterial vs viral CAP than CRP, WBC, ESR

• Studies vary on cut-off values, but can agree that a cut-off value of 0.25 ng/mL can be used

• Data in adults, and more recently in pediatrics, show that PCT can decrease antibiotic start, decrease duration of antibiotics, and subsequently decrease number of antibiotic adverse effects

Procalcitonin (PCT)Background5,6,7,8,9

• Now available with a quick turnaround time (TAT): STAT = 1 hour vs routine = 4 hours

• Sending STAT PCT at presentation if getting bloodwork

• Start antibiotics in patients with PCT >0.25 ng/mlo If PCT ≤0.25 ng/mL and concern for pneumonia developing, can repeat levels in 6-8 hours

• Consider stopping antibiotics if PCT ≤0.25 ng/mL

• For those staying inpatient for longer period of time: o Consider repeating PCT at day 4-5 of admission, and then every 2 days, and stop antibiotics when PCT ≤0.25

ng/mL

Procalcitonin (PCT) Utilization

• A note on respiratory BIOFIRE:o Tests are expensive

o Often do not alter course of management

o Recommend sending off influenza, RSV and STAT procalcitonin first as PCT can help determine between viral and bacterial causes (as BIOFIRE cannot)

o BIOFIRE is only routinely recommended to test for pertussis

Respiratory BIOFIRE

• Several recent publications highlight the lack of efficacy of azithromycin in the use of pediatric CAP10

• Definite lack of efficacy in children ≤5 years old

• Questionable efficacy in older patients

Azithromycin

Age Pneumonia Atypical Pneumonia CAP

≤5 years old 3 15 62

>5 years old 5 17 81

Total 8 32 143

Connecticut Children’s Usage of Azithromycin

• Large proportion of our azithromycin use for CAP is those under 5 (against pathway recommendations)

• Azithromycin usage is now RESTRICTED via Antimicrobial Stewardship Program (ASP)

• 2007 IDSA guidelines for CAP1: o empiric tx for MRSA with shock, necrotizing/cavitary PNA, or risk factors for MRSA (drug use, prior flu, prior

antibiotic use)

o Early discontinuation of empiric MRSA tx if negative cultures (if S aureus doesn’t grow, likely not cause of infection)

• Problem: can only obtain a good respiratory culture 30-50% of the time

MRSA in CAP Background

• New evidence to support the use of MRSA nasal PCR to rule out MRSA pneumonia quickly11,12

o 20% of people are persistently colonized with S Aureus (60% are intermittent carriers)

o MRSA colonization usually precedes infection

o PCR testing:

– Will remain positive regardless of organism viability and can be obtained up to 48 hours after MRSA treatment begun

– ≥95% negative predictive value in pneumonia

– PCR test results within 1-5 hours

– If negative: can reduce exposure and toxicity from vancomycin

– If positive: possible that infection is caused by MRSA as patient is colonized and colonization often precedes infection; will support quicker time to goal concentration

MRSA Nasal PCRBackground

• Add MRSA nasal PCR to patients who need vancomycin from pneumonia

• Stop vancomycin if MRSA nasal swab negative

MRSA Nasal PCRUtilization

This is the Community Acquired Pneumonia Clinical Pathway.

We will be reviewing each component in the following slides.

This pathway is meant for children 2 months and older with suspected CAP

Exclusion Criteria:• Less than 2 mo of age• Certain underlying conditions:

• immunocompromise, congenital heart disease, bronchopulmonary dysplasia, sickle cell, neuromuscular disease

• Hospital acquired pneumoina• Aspiration pneumonia

Inclusion Criteria: 2 mo old – 18 yr old with suspected CAPExclusion Criteria: <2 mo, immunocompromised, congenital heart disease, BPD, sickle cell,

neuromuscular disease, aspiration PNA, hospital acquired PNA

Management in the ED is focused on diagnosing CAP and initiating appropriate treatment based on presenting symptoms.

Not every patient with CAP requires admission.

In ED:

Admission Criteria: Hypoxemia <90% Increased WOB/respiratory distress/tachypnea Lethargy Failed outpatient treatment on ≥48 hours of therapy Concern for compliance

Work-Up: CXR Consider CBC with Diff, Lytes, STAT procalcitonin,

blood culture (if under-immunized or moderately ill)

Consider viral testing in season (influenza, RSV only; BIOFIRE only if concerned for pertussis)

Nursing Care: Supplemental O2 if SpO2<90% Place PIV if indicate

Patients with Mild to Moderate CAP are generally safe for Med/Surg admission.

Severe CAP is defined as patients with cyanosis, impeding respiratory distress, sepsis. • Provider concern can also be reason for PICU

evaluation

Admission Criteria: Hypoxemia <90% Increased WOB/respiratory distress/tachypnea Lethargy Failed outpatient treatment on ≥48 hours of therapy Concern for compliance

Mild-Moderate CAP Severe CAP*

PICU AdmitInpatient Med/Surg Admit

* Severe CAP Definition:

Cyanosis Severe

respiratory distress or impending respiratory failure

Sepsis PICU concern

Mild/Moderate CAP management:

Assess Immunization status and History:• Up to date with Hib and Pneumococcus at 2, 4, &

6 months?• Failed outpatient therapy?• Empyema?

Mild-Moderate CAP

Obtain (if not already done): CXR, CBC/Diff, STAT Procalcitonin Blood culture if moderately ill PIV if poor PO

Fully Immunized (UTD

for Hib, pneumococcal @2,4,6 mo) +

No emypema, or failed outpt tx

Not fully immunized OR empyema/abscess is

present

Inpatient Med/Surg Admit

Mild/Moderate CAP management:

• Ampicillin every 6 hours will be the lone antibiotic of choice for most patients

• Standard dosing: 200 mg/kg/day• Outpatient treatment failure dosing: 400

mg/kg/day• High dose Amoxicillin may be used in well

appearing patients

Outpatient treatment failure is considered when a patient does not improve on at least 48 hours of the correct antibiotic at the correct dose• High dose Ampicillin or Ceftriaxone

Consider stopping antibiotics if procalcitonin

≤0.25 ng/mL.

Ampicillin 200 mg/kg/day div q6hr (max 2 g/dose)

ORAmoxicillin 90 mg/kg/day div 3 doses (max 1 g/dose)

If PCN allergy:Ceftriaxone 50 mg/kg/day (max 2 g/dose) OR Clindamycin 40 mg/kg/day div 3 or 4 doses (max 1800 mg/day)

If failed outpt treatment:Ampicillin 400 mg/kg/day div q6hr (max 2 g/dose) ORCeftriaxone 75 mg/kg/day div 2 doses (max 2 g/dose)

Fully Immunized (UTD for Hib, pneumococcal

@2,4,6 mo) + No emypema, or

failed outpt tx

Mild/Moderate CAP managment:

If NOT fully vaccinated OR Empyema present – need to cover both resistant pneumococcus and H. flu• Send Blood Culture if not already done• Ceftriaxone is the antibiotic of choice

• Levofloxacin may be used in the case of Cephalosporin allergy

• Consider surgery consult for moderate/large empyema


present


≤0.25 ngLmL.

Ceftriaxone 75 mg/kg/day div 2 doses (max 2 g/dose)

If Cephalosporin allergy: Levofloxacin (6 mo-<5 yr: 20 mg/kg/day div 2 doses; 5-<10 yr: 14 mg/kg/day div 2 doses; ≥10 yr: 10 mg/kg/day daily); max 750 mg/day

Blood culture if not done

In either treatment arm:

Consider discontinuing antibiotics if procalcitonin is less than or equal to 0.25 ng/mL


present


≤0.25 ngLmL.

Ceftriaxone 75 mg/kg/day div 2 doses (max 2 g/dose)

If Cephalosporin allergy: Levofloxacin (6 mo-<5 yr: 20 mg/kg/day div 2 doses; 5-<10 yr: 14 mg/kg/day div 2 doses; ≥10 yr: 10 mg/kg/day daily); max 750 mg/day

Blood culture if not doneConsider stopping

antibiotics if procalcitonin ≤0.25 ng/mL.

Ampicillin 200 mg/kg/day div q6hr (max 2 g/dose)

ORAmoxicillin 90 mg/kg/day div 3 doses (max 1 g/dose)

If PCN allergy:Ceftriaxone 50 mg/kg/day (max 2 g/dose) OR Clindamycin 40 mg/kg/day div 3 or 4 doses (max 1800 mg/day)

If failed outpt treatment:Ampicillin 400 mg/kg/day div q6hr (max 2 g/dose) ORCeftriaxone 75 mg/kg/day div 2 doses (max 2 g/dose)

Fully Immunized (UTD for Hib, pneumococcal

@2,4,6 mo) + No emypema, or

failed outpt tx

Severe CAP management:

Patients with severe CAP will be more ill on presentation, and will typically require PICU admission

On admission, work up labs should be completed if not done already.

IF starting on anti-MRSA antibiotic, please obtain MRSA PCR nasal swab

Severe CAP*

PICU Admit

Obtain (if not already done): CXR, CBC/Diff, STAT

Procalcitonin Blood culture PIV MRSA PCR nasal swab

Severe CAP management:

In patients with severe CAP, treatment starts with more broad spectrum antibiotics and MRSA coverage. • Ceftriaxone AND Vancomycin • If the patient has a cephalosporin allergy can use

Levofloxacin AND Vancomycin

Antibiotics and Duration of treatment should be adjusted based on ongoing lab assessment.

Initial Antibiotics: Ceftriaxone 75 mg/kg/day div 2 doses (max 2 g/dose)

ANDVancomycin 15 mg/kg/dose q6hr (≥18 yr old: q8hr; max initial dose: 1 g/dose)

If Cephalosporin allergy: Levofloxacin (6 mo-<5 yr: 20 mg/kg/day div 2 doses; 5-<10 yr: 14 mg/kg/day div 2 doses; ≥10 yr: 10 mg/kg/day daily); max dose 750 mg/day

ANDVancomycin (dosed as above)

Ongoing Management:

Labs: Stop vancomycin if MRSA

nasal swab negative Trend procalcitonin on

day 4 of admission; then every 2 days.

Duration of treatment: 14 days If procalcitonin ≤0.25 ng/

mL prior to 14 days, consider stopping antibiotics.

Special Considerations: MRSA, Atypical, and Influenza

Certain patients will need additional treatment based on history, physical symptoms, and developing symptoms

• Suspect MRSA then ADD Vancomycin• Suspect atypical IN PATIENT >5 YEARS OLD

then CONSIDER addition Azithromycin (evidence lacking)

• Unless already on Levofloxacin• Suspcted or known Influenza then ADD

Oseltamavir

Add Azithromycin ≥6 mo old: 10

mg/kg (max 500 mg/dose) x1-2 days, then 5 mg/kg (max 250 mg/dose) to complete 5 days

<6 mo old: 10 mg/kg x5 days

Not needed if using levofloxacin.

Add Oseltamavir Premature infants

(<37 wks): 2 mg/kg/day div 2 doses

0-8 mo: 6 mg/kg/day div 2 doses (max 75 mg/dose)

9-23 mo: 7 mg/kg/day div 2 doses

>24 mo: 4 mg/kg/day div 2 doses

Add Vancomycin 15 mg/kg/dose q6hr (≥18 yr old: q8hr) Max initial dose: 1

g/dose Adjust dose based

on trough to maintain 15-20 mg/l

Send: MRSA nasal swab and consider stopping vancomycin if negative

Suspect MRSA?(worsening empyema/

abscess despite adequate treatment, sepsis, recent

proven influenza infection)

Suspect Atypical?(>5 yrs old AND one of following: sub-acute

presentation, interstitial infiltrates, failed empiric

tx for pneumococcus x48hrs, bullous myringitis

OR 2-3 mo olds for chlamydia coverage

OR any age for pertussis coverage )

Suspect Influenza?(sick contacts w influenza,

coryza, sore throat, myalgia, (+) viral study)

Special Considerations

Add Oseltamavir Premature infants

(<37 wks): 2 mg/kg/day div 2 doses

0-8 mo: 6 mg/kg/day div 2 doses (max 75 mg/dose)

9-23 mo: 7 mg/kg/day div 2 doses

>24 mo: 4 mg/kg/day div 2 doses

Suspect Influenza?(sick contacts w influenza,

coryza, sore throat, myalgia, (+) viral study)

Special Considerations

New AAP guidelines for influenza:• ALL hospitalized patients with positive flu PCR

should receive oseltamivir treatment (regardless of duration of symptoms)

• If patients are immunocompromised or severely ill with influenza and not improving after 5 days of therapy:

• Re-test for influenza to determine if any additional anti-influenza therapy is needed

Pathogen Identification:

Note that antimicrobial treatment should be adjusted at any point if a positive pathogen is identified.

• Including positive blood cultures

**Antimicrobial therapy should be narrowed if

pat hogen i s confirmed.

Discharge Planning:

Consider change from IV to PO antibiotics after 2-3 days of clinical improvement

Can consider discharge once discharge criteria are met and when clinically appropriate

∆ IV to PO after 2-3 days clinical improvement and if clinically appropriate

Discharge Criteria: O2 >90% on RA x24 hr, decreased

fever x24 hr, increased activity/appetite, baseline mentation, compliance w treatment, f/u in place

Discharge Medications:

Total duration of treatment: 7 days for mild-moderate CAP; 14 days for severe CAP

PO Amoxicil lin (if fully immunized; likely pneumococcus) OR PO Augment in (if under-immunized)

90 mg/kg/day div 3 doses (max 1 gram/dose)

If PCN allergy: Clindamycin PO 40 mg/kg/day div 3 or 4 doses (max 1800 mg/day) OR

Cefdinir 14 mg/kg/day div 2 doses (max 600 mg/day)

If MSSA concern: Augmentin (dosing as above)

If documented resistant pneumococcus: Levofloxacin (dosing as above)

If atypical PNA: Azithromycin (see dosing above) x5 days total

If influenza: Oseltamivir (see dosing abov e) x5 days tot al

Transition to oral antibiotics:

• High dose Amoxicillin or Augmentin (90 mg/kg/day) for 7 days will be standard treatment for most patients

• Consider other medications based on the clinical circumstances.



























Please note:

• Cefdinir is inferior to high dose amoxicillin or augmentin TID for the treatment of pneumococcal pneumonia

• Augmentin only provides additional H. flu and staph coverage (compared to amoxicillin)

• Antibiotics:oAmpicillin is drug of choice in most cases!

–Use high dose (400mg/kg/day) for failed outpatient treatment

oUse Ceftriaxone if not fully immunized (Prevnar and Hib), if empyema present or if severely ill

o If (+) blood culture, use sensitivities

Review of Key Points

• Procalcitonin is a useful biomarker to determine between bacterial vs viral CAP

• Procalcitonin can be utilized to determine antibiotic duration

• MRSA nasal PCR can be utilized to determine if vancomycin is necessary

• Azithromycin is not typically indicated for CAP and will be restricted in its usage

• Duration of antibiotics:o Mild/Moderate – 7 days

o Severe - 14 days (but use procalcitonin to help determine duration)

Review of Key Points

• Percentage of eligible patients treated per pathway

• Percentage of patients with order set usage

• Percentage of patients with appropriate inpatient antibiotic selection

• Percentage of patients with correct inpatient discharge antibiotic selection

• Percentage of patients with correct inpatient discharge antibiotic dosage

• Average duration of antibiotic coverage (inpatient + outpatient prescription)

• Percentage patients who had a CBC, who also had procalcitonin drawn

• Percentage of patients with a procalcitonin level ≤0.25 who receive an antibiotic

• Percentage of patients who receive vancomycin or linezolid

• Percentage of patients with negative MRSA PCR, and vancomycin or linezolid discontinued

• Admit length of stay (days)

Quality Metrics

• Jennifer Girotto, PharmD, BCPPS, BCIDPo Connecticut Children’s Antimicrobial Stewardship Program Co-Director

o Infectious Disease Residency Director

• Grace Hong, APRNo Connecticut Children’s Infectious Disease and Immunology

• Anand Sekaran, MDo Connecticut Children’s Pediatric Hospital Medicine

Pathway Contacts

• 1Bradley, J.,m Byington, C. et al. The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical PracticeGuidelines by the Pediatric Infectious Disease Society and the Infectious Diseases Society of America. Clinical Infectious Diseases. Volume 53. Issue 7, Oct 2011, Pages e25-e76. http://doi.org/10.1093/cid/cir531.

• 2Jain, S. Williams, D. Arnold, S. et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Children. N Engl J Med 2015; 372:835-845; DOI 10.1056/NEJMoa1405870.

• 3Self WH, Williams DJ, Zhu Y, Ampofo K, Pavia AT, Chappell JD, et al. Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired PneumoniaExternal J Infect Dis. DOI: 10.1093/infdis/jiv323

• 4Self WH, Wunderink RG, Williams DJ, Zhu Y, Anderson EJ, Balk RA et al. Staphylococcus aureus community-acquired pneumonia: prevalence, clinical characteristics, and outcomesExternal. Clin Infect Dis. 2016 May 8. pii: ciw300.

• 5Shuetz, P., Leykum, L.K. Procalcitonin. Hosp Med Clin 1. 2012. e300-e312. DOI: 10.1016/j.ehmc.2012.04.005.

• 6Simon L, Gauvin F, Amre DK, et al. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004. 39:206-17.

• 7Cuquemelle, E., Soulis, F. et al. Can Procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Medicine. 2011. Vol.37(5). Pp796-800.

• 8Schuetz, P., Christ-Crain, M., et al. Guidance of Antibiotic Therapy with Procalcitonin in Lower Respiratory Tract Infections: Insights into the ProHOSP trial. 2010. p88-92. https://doi.org/10.4161/viru.1.2.10488

• 9Stockmann C, Ampofo K, Killpack J, Williams DJ, Edwards KM., Grijalva C, et al., Procalcitonin accurately identifies hospitalized children with low risk of bacterial community-acquired pneumonia. J Pediatric Infect Dis Soc. 2017 Feb 3. doi: 10.1093/jpids/piw091. [Epub ahead of print]: https://academic.oup.com/jpids/article-abstract/doi/10.1093/jpids/piw091/2966998/Procalcitonin-Accurately-Identifies-Hospitalized?redirectedFrom=fulltextExternal

• 10Vardakas, K., Trigkidis, K., et al. The dilemma of monotherapy or combination therapy in community-acquired pneumonia. Eur J Clin Invest. 2017. 47:e12845.

• 11Carr, A., Daley, M., et al. Clinical Utility of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screening for Antimicrobial Stewardship: A Review of Current Literature. DOI: 101002/phar.2188.

• 12Parente, D., Cunha, C., Mylonakis E., Timbrook, T. The Clinical Utility of Methicillin Resistant Staphylococcus aureus (MRSA) Nasal Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis with Antimicrobial Stewardship Implications. Clin Infect Dis. 2018. 67(1):1-7.

References

Thank You!

About Connecticut Children’s Clinical Pathways ProgramClinical pathways guide the management of patients to optimize consistent use of evidence-based

practice. Clinical pathways have been shown to improve guideline adherence and quality outcomes, while decreasing length of stay and cost. Here at Connecticut Children’s, our Clinical Pathways Program aims to deliver evidence-based, high value care to the greatest number of children in a diversity of patient settings.

These pathways serve as a guide for providers and do not replace clinical judgment

This Educational Module was edited by:

Abby Theriaque, APRN

Educational Module Specialist

Clinical Pathways Community Acquired Pneumonia (CAP)•EPIC (Etiology of Pneumonia in the Community)...

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