CAP

1. Community-Acquired
Pneumonia
Eric Mortensen, MD, MSc, FACP

2. Community-Acquired
Pneumonia (CAP)
• Eighth leading cause of death in the U.S.
• Leading infectious cause of death
• Since 1950 mortality has been stable or
increasing
• Increased incidence with aging of the U.S.
population

3. Impact of CAP
• “More than 1.2 million Americans- roughly
equivalent to the population of Dallas- were
hospitalized for pneumonia in 2006, making
this lung infection the most common reason
for admission to the hospital other than for
childbirth…”
AHRQ News and Numbers July 2, 2008

4. Case Presentation
• 72 year old male
• C/O cough and fever/chills
• Past medical history significant for
– Stroke
– Chronic kidney disease
• Lives with wife at home

5. Physical Exam Findings
• Pulse 110
• Respiratory rate 32
• Blood pressure 150/72
• Temperature 39.2o
C
• Confused

6. Labs
• Lab results
– BUN 45
– Partial pressure of arterial oxygen 58 mm Hg

8. Severity of Illness Scores
• Pneumonia severity index (PSI)
– 20 variables
• CURB-65
– Confusion
– Urea > 20
– Respiratory rate > 30
– Blood pressure, systolic < 90 or diastolic < 60
– Age > 65

9. Site of Care Decision
• PSI
– Broken into five classes
– Classes I and II outpatient treatment unless
other mitigating factors
• CURB-65
– 0-1 factors outpatient treatment
– 2 factors medicine wards
– >3 consider ICU admission

10. Severity of Illness
• Pneumonia severity index class
– Class V
• CURB-65
– Confusion
– Urea > 20
– Respiratory rate > 30
– Blood pressure SBP < 90 or DBP <60
– Age > 65

11. Definition of Severe CAP
• Minor criteria
– Respiratory rate >
30/min
– PaO2/FiO2 < 250
– Multilobar infiltrates
– Confusion
– BUN > 20 mg/dl
– Platelet < 100k
– Temp <36o
C
– Hypotension requiring
fluid resuscitation
• Major criteria
– Invasive mechanical
ventilation
– Septic shock with need
for vasopressors

12. CAP or HCAP?
• HCAP = health care associated pneumonia
• Very controversial!!!
• Potential criteria include:
– Hospitalization > 2 days in preceding 90 days
– Nursing home residence
– Home infusion therapy
– Home wound care
– Family member with drug resistant pathogen
– Chronic dialysis
– Immunosuppression

13. Etiology of CAP
• CAP is not a homogeneous condition
– True community-acquired versus healthcare
acquired e.g. nursing home
• Pathogens not found in > 50% of cases

14. Most Common Etiologies
Ambulatory Hospital Ward ICU
S. pneumoniae
M. pneumoniae
H. influenzae
C. pneumoniae
Viruses
S. pneumoniae
M. pneumoniae
H. influenzae
C. pneumoniae
Legionella
Aspiration
Viruses
S. pneumoniae
Legionella
H. influenzae
Gram (-) bacilli
S. Aureus
Viruses
File T et al. Lancet 2003

15. Community-Acquired MRSA
• Increasing number of cases identified
• Defined as community-acquired if no
hospitalization or procedure < 1 year
• Usually sensitive to numerous antibiotics
– clindamycin, bactrim, and doxycycline
• Severe necrotizing pneumonia
– Panton-Valentine Leukocidin gene
– Survival < 20%

16. What is the most likely
organism?
Streptococcus pneumoniae

17. Clinical Practice Guidelines for
CAP
• ATS- 1993 and 2001
• IDSA- 1998, 2000, and 2003
• BTS- 1993 and 2001
• CIDS/CTS- 1993 and 2000
• CDC- 2000
• ATS/IDSA- 2007
Mandell,Clin Infect Dis, 2007. 44 Suppl 2: p. S27

18. Guideline Recommendations
Empiric Outpatient Therapy
• No significant risk factors for drug resistant
S. pneumoniae (DRSP)
– Macrolide
– Doxycycline

19. Guideline Recommendations
Empiric Outpatient Therapy
• Has risk factors for DRSP or significant
comorbid conditions
– Anti-pneumococcal fluoroquinolone
β-lactam + macrolide/doxycycline
• Preferred- high dose amoxicillin or
amoxicillin/clavulanate
• Alternates- ceftriaxone, cefpodoxime, or cefuroxime

20. Risk Factors for DRSP
• Age > 65 years
∀β-lactam or macrolide therapy within the
past 6 months
• Alcoholism
• Medical comorbidities
• Immunosuppressive therapy
• Exposure to a child in day care
Cambell, Clin Infect Dis 1998;26: 1188

21. Guideline Recommendations
Empiric Ward Therapy
∀β-lactam + macrolide/doxycycline
– Cefotaxime, ceftriaxone, ampicillin, ertapenem
• Anti-pneumococcal fluoroquinolone alone

22. Guideline Recommendations
Empiric ICU/SCAP Therapy
∀β-lactam + azithromycin or respiratory
fluoroquinolone
– Cefotaxime, ceftriaxone, ampicillin-sulbactam
• If penicillin allergic
– Fluoroquinolone + aztreonam

23. Guideline Recommendations
Risk Factors for Pseudomonas
• Antipseudomonal β-lactam + high dose
ciprofloxacin or levofloxacin
– Piperacillin-tazobactam, cefepime, imipenem,
meropenem
• Antipseudomonal β-lactam+ aminoglycoside+
azithromycin
• Antipseudomonal β-lactam+ aminoglycoside+
ciprofloxacin or levofloxacin

24. Guideline Recommendations
CA-MRSA
• Addition of vancomycin or linezolid to
empiric antimicrobial regime

25. What empiric antibiotic
regime(s) should this patient be
given?
β-lactam + macrolide
β-lactam + fluoroquinolone
or
Fluoroquinolone + clindamycin

26. Guideline-Concordant Antimicrobial
Therapy and Mortality
• 420 subjects hospitalized at 2 tertiary hospitals
– 20% were initially admitted to the ICU
– 30-day mortality was 9.8%
• After adjusting for potential confounders the use
of non-guideline concordant antibiotics was
associated with increased mortality
– Odds ratio 5.7, 95% CI 2-16
Mortensen et al. AJM, 2004; 117:726

27. β-Lactam vs β-Lactam–Macrolide Combination Treatment in
CAP: A Randomized Noninferiority Trial
Gain N et al. JAMA Intern Med. 2014

28. Antibiotic Treatment Strategies for CAP
Postma DF et al. N Engl J Med 2015

29. 90-day Mortality by Azithromycin Use
Odds ratio 0.73, 95% CI 0.70-0.76
Mortensen et al. JAMA 2014

30. Time to First Cardiac Event by
Azithromycin Use
Outcome OR 95% CI
MI 1.17 1.08-1.25
Arrhythmia 0.99 0.95-1.02
Heart failure 1.01 0.97-1.04
Any CV 1.01 0.98-1.05
Mortensen et al. JAMA 2014

31. Azithromycin and Pneumonia
• Azithromycin use associated with
lower mortality but higher rate of MI
– NNT to prevent 1 death- 21
– NNH to cause 1 MI- 144
– Net benefit: 7 deaths averted for each non-
fatal MI
Mortensen et al. JAMA 2014

32. Switching Antimicrobial Therapy
• Switch from IV to PO
– Continuation of similar antimicrobial coverage
• Clinical stability criteria
• Ability to tolerate antibiotics by mouth
• Afebrile (<100o
F) on two occasions 8h apart
• Decreasing white blood cell count
• Improving symptoms: cough, dyspnea and fevers

33. Early Switch for Patients with
Bacteremic Pneumococcal CAP
• 75 patients
• Intervention to promote early switch of IV to PO
antibiotic therapy
• Mean Duration of IV Therapy- 3 days
• LOS reduced by 2 days in study patients
– 4 days versus 6 days
• Clinical cure reported in 99% of patients
Ramirez, JA et al. Arch Intern Med. 2001;161:848

34. Duration of Therapy
• Very few studies have examined length of
therapy
• At least 5 days of therapy recommended
• Levofloxacin
– 750mg of levofloxacin for 5 days equivalent to
500mg for 10 days
Dunbar, LM et al. CID. 2003;37:752

35. Procalcitonin (PCT)
• Stimulated by bacterial endotoxin
• Viral and localized infection have lower PCT
levels than systemic infections
• Autoimmune and neoplastic disease do not induce
• Available at VA

36. PCT and Diagnosis
Nyamande Int J TB Lung Dz 2006; 10: 510
P=0.0004

37. PCT and Antibiotics
• RCT to examine whether PCT guidance
associated with less antibiotic use
• PCT strata
– <0.1 Antibiotics strongly discouraged
– 0.1-0.25 Antibiotics discouraged
– 0.25-0.5 Antibiotics advised
– >0.5 Antibiotics strongly recommended
Christ-Crain AJRCCM 2006 174: 84

38. PCT and Antibiotic Discontinuation

39. PCT and Antibiotic Duration

40. PCT/CRP and Treatment Failure
• Prospective cohort of 453 CAP patients
– 18% treatment failures
• CRP & PCT higher in failures
– Day 1
• CRP: 13.6 vs. 23.2
• PCT: 0.5 vs. 1.5
– Day 3
• CRP: 4.5 vs. 12.1
• PCT 0.3 vs. 0.5
Menendez Thorax 2008;

41. At Time of Discharge or Soon
After
• Pneumococcal vaccination
• Influenza vaccination
• Follow up chest imaging

42. Pulmonary Malignancy after
Pneumonia
Mortensen et al. Am J Med 2010

43. Summary
• Use CURB-65 for admission decisions
• Use guideline concordant antibiotics
• Treat for at least 5-7 days (not only IV)
• Consider using PCT (when available) in addition
to clinical status to guide treatment decisions

44. Questions?
Eric.Mortensen@UTSouthwestern.edu