1. Community Acquired Pneumonia
Andy Hale, MD
Molly Brett, MD

2. Welcome to the module on Community Acquired Pneumonia!!
Please take this brief pre-module quiz

3. Table of contents Introduction to CAP: definitions, epidemiology
What causes CAP?
Overview of specific organisms
Risk stratification
Diagnosis of CAP
Treatment of CAP

4. First, a few definitions…
Community-acquired pneumonia (CAP) is pneumonia acquired outside a hospital or long-term care facility.
Occurs within 48 hrs of hospital admission or in a patient presenting with pneumonia who does NOT have any of the following characteristics:
Hospitalized in acute care hospital for 2 or more days within 90 days of infection.
Resides in nursing home or long term care facility.
Received recent IV antibiotic therapy, chemo, or wound care within the past 30 days of the current infection.
Attends hemodialysis.

5. CAP Epidemiology
Pneumonia (together with influenza) was the 9th leading cause of death in the USA in 2010, causing 50,000 deaths according to the CDC.
Higher burden in older adults: among people older than 85 years old, estimated 1 in 20 develop CAP each year. 1
2010 study demonstrated that the overall annual costs associated with CAP had grown to more than $17 billion. 2
1) Jackson ML, Neuzil KM, Thompson WW, Shay DK, Yu O, Hanson CA, et al. The burden of community-acquired pneumonia in seniors: results of a population-based study. Clin Infect Dis. Dec ;39(11):
2) File TM Jr, Marrie TJ. Burden of community-acquired pneumonia in North American adults. Postgrad Med. Mar 2010;122(2):

6. Who is at risk of a bad outcome from CAP?
Alterations in mental status
Alcoholics, epileptics, stroke patients, uremia
Underlying lung disease
Chronic hypoxia, COPD, asthma, ILD
Cilia motility disorder
Kartagener’s, cystic fibrosis
Altered lung anatomy
Lung cancer, bronchiectasis, obstructions
Immunocompromised

7. Table of contents Introduction to CAP: definitions, epidemiology
What causes CAP?
Overview of specific organisms
Risk stratification
Diagnosis of CAP
Treatment of CAP

8. What causes CAP? There are >100 organisms, but those below are most common. 1, 2, 3.
Overall rates
Outpatient CAP
Inpatient CAP
Unknown
51%
54%
60%
Streptococcus pneumoniae
17%
10%
18%
Mycoplasma pneumoniae
12% 2%
Chlamydophila pneumoniae 9%
Identified virus 5%
Haemophilus influenzae
Legionella pneumophila 1% 4%
Staph. aureus
We don’t know most of the time!
1) Marrie TJ, et al. Etiology of community-acquired pneumonia treated in an ambulatory setting. Resp Medicine 2005; 99:60.
2) Cilóniz C et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66:340.
3) Restrepo MI et al.. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133:610.

9. How often is an organism isolated?
RARELY! ~10%
But that’s OK. Empiric therapy usually works (as we will get to).
It’s important to know what organisms are most common so that we can choose APPROPRIATE empiric therapy, as it varies by patient and setting.

10. Outpatient CAP: atypicals, s. pneumo
Organism
Overall rates
Outpatient CAP
Inpatient CAP
Unknown
51%
54%
60%
Streptococcus pneumoniae
17%
10%
18%
Mycoplasma pneumoniae
12% 2%
Chlamydophila pneumoniae 9%
Identified virus 5%
Haemophilus influenzae
Legionella pneumophila 1% 4%
Staph. aureus
Less common in inpatient CAP.
In outpatient settings, “atypicals” (mycoplasma and chlamydophilia pneumoniae) are more prevalent (except legionella, an atypical seen in inpatients).
1) Marrie TJ, et al. Etiology of community-acquired pneumonia treated in an ambulatory setting. Resp Medicine 2005; 99:60.
2) Cilóniz C et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66:340.
3) Restrepo MI et al.. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133:610.

11. Inpatient CAP: s. pneumo>> s. aureus, legionella, h. flu
Organism
Overall rates
Outpatient CAP
Inpatient CAP
Unknown
51%
54%
60%
Streptococcus pneumoniae
17%
10%
18%
Mycoplasma pneumoniae
12% 2%
Chlamydophila pneumoniae 9%
Identified virus 5%
Haemophilus influenzae
Legionella pneumophila 1% 4%
Staph. aureus
In inpatient CAP, think about gram positives (especially s. pneumo). Less common causes include haemophilus influenzae and legionella.
1) Marrie TJ, et al. Etiology of community-acquired pneumonia treated in an ambulatory setting. Resp Medicine 2005; 99:60.
2) Cilóniz C et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66:340.
3) Restrepo MI et al.. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133:610.

12. What causes CAP?
Organism
Overall rates
Outpatient CAP
Inpatient CAP
Unknown
51%
54%
60%
Streptococcus pneumoniae
17%
10%
18%
Mycoplasma pneumoniae
12% 2%
Chlamydophila pneumoniae 9%
Identified virus 5%
Haemophilus influenzae
Legionella pneumophila 1% 4%
Staph. aureus
Gram positives are the most common overall cause of CAP, followed by atypicals. Gram negatives are least common.
1) Marrie TJ, et al. Etiology of community-acquired pneumonia treated in an ambulatory setting. Resp Medicine 2005; 99:60.
2) Cilóniz C et al. Microbial aetiology of community-acquired pneumonia and its relation to severity. Thorax 2011; 66:340.
3) Restrepo MI et al.. A comparative study of community-acquired pneumonia patients admitted to the ward and the ICU. Chest 2008; 133:610.

13. What causes CAP?
Let’s go through a few specific bacteria, and talk about unique features.

14. Strep. pneumoniae
Most common cause of CAP in inpatient, outpatient, and ICU setting (10-18% of cases)
Urine antigen test:
80% sensitive, 97% specific
Can be used to rule-out S. pneumo effectively
Rarely used at BIDMC (a send out lab, so less clinically useful)
Gram stain: gram (+) cocci in pairs and short chains

15. Strep. pneumoniae Colonizes the nasal tract in 50% of people.
Increased risk for resistant strains in patients who have previously received antibiotics.
Resistance against commonly used antibiotics (eg: azithromycin) is a growing concern.
Note: the pneumococcal vaccine is discussed separately, at the end of the module.

16. MRSA Community Acquired PNA (CA-MRSA)
MRSA CAP is rare:
Only 1-4% of CAP is from s. aureus, and just 9% of these cases are MRSA.
Typically in the elderly after influenza infection and in the young.
In one study, 71% of CA-MRSA was after influenza infection, usually in the elderly.1
High case mortality:
In one study, of 15 CA-MRSA pneumonia cases, 5 died1
Typically presents as a severe necrotizing pneumonia
Multiple infiltrates or cavities on CXR
Gram stain: gram (+) cocci in clusters
1) Hageman JC et al. Severe community-acquired pneumonia due to Staphylococcus aureus, influenza season. Emerg Infect Dis. 2006;12(6):894.

17. CA-MRSA CAP: Clinical and pathologic manifestations
CA-MRSA gram stain
CA-MRSA necrotizing PNA on CT
Gram (+) cocci in clusters.
(Quiz yourself: how does this differ from gram stain appearance of S. pneumo?)
Typically presents as a severe necrotizing pneumonia with multiple infiltrates or cavities on CXR and CT.

18. CA-MRSA CAP: Clinical and pathologic manifestations
CA-MRSA gram stain
CA-MRSA necrotizing PNA on CT
Gram (+) cocci in clusters.
(Quiz yourself: how does this differ from gram stain appearance of S. pneumo?)
“Quiz yourself” answer:
Strep pneumo appears on gram stain as gram positive cocci in pairs and short chains, whereas staph aureus, seen above, classically appears as GPCs in clusters.
Typically presents as a severe necrotizing pneumonia with multiple infiltrates or cavities on CXR and CT.

19. Mycoplasma pneumoniae
Mycoplasma are the smallest organisms that can survive alone in nature (not visible on gram stain!)
Hard to culture, so won’t show up on typical “sputum culture” results.
Has no cell wall (Quiz yourself: Would a penicillin work?)
Mycoplasma seen on electron microscopy
Image courtesy of

20. Mycoplasma pneumoniae
Mycoplasma are the smallest organisms that can survive alone in nature (not visible on gram stain!)
Hard to culture, so won’t show up on typical “sputum culture” results.
Has no cell wall (Quiz yourself: Would a penicillin work?)
Mycoplasma seen on electron microscopy
“Quiz yourself” answer: Beta lactam antibiotics work by inhibiting bacterial cell wall synthesis, so a penicillin would have no efficacy on bacteria like mycoplasma that lack a cell wall.
Image courtesy of

21. Mycoplasma pneumoniae: clinical manifestations
Typically seen in younger adults
Most common cause of “walking pneumonia”
Symptoms typically develop over 1-3 weeks (slower onset than “typical” bacterial PNA).
Usually a dry cough
Antibodies against M. pneumoniae antigens can cross react with human brain cells and erythrocytes – more on this in the next slide!
WBC normal in 75 to 90 percent
Mycoplasma pneumonia classically has a bilateral reticulonodular pattern on CXR
Image courtesy of

22. Mycoplasma pneumoniae: cold agglutination
Cold agglutinins = IgM against RBC antigens.
Antibodies against M. pneumoniae antigens can cross-react with RBCs.
Poorly bind to antigens at normal body temp; bind maximally at lower temps.
Extravascular clearance > intravascular hemolysis
Dx: positive Coombs test
Pathophysiology of cold agglutinin disease:
IgM autoantibodies bind antigens on RBC surface
Binding of antibodies activates classical pathway of complement system
Membrane attack complex forms
Intravascular hemolysis
Opsonization by complement proteins
Clearance in reticuloendothelial system (extravascular)

23. Chlamydophila pneumoniae
Most common in patients ages 7-40, though reinfection common in the elderly.
Mild PNA: dry cough, malaise, headache of gradual onset over 3-4 weeks.
Unlike other respiratory infections, which peak in the winter, C. pneumoniae does not vary significantly by season.
HISTOLOGY:
Small obligate intracellular organism: not seen on gram stain
Special stain for Chlamydophilia in bronchial cells.

24. Legionella Causes 2 distinct diseases: 1) Legionnaire's Disease
Respiratory infection
2) Pontiac fever
More mild form of Legionella infection
Acute, self-limited, febrile illness
Symptoms include fever, malaise, chills, fatigue, and headache, with NO respiratory complaints
Usually no antibiotics needed
Legionella seen on electron scanning microscopy.
Image courtesy of

25. Legionnaire's Disease: Clinical manifestations
Transmitted by inhalation of contaminated aerosolized water (e.g via air conditioning systems)
Distinguishing features:
High fever (> 103F), often with relative bradycardia (Faget’s sign)
Hyponatremia
Mild LFT abnormalities
GI symptoms (especially diarrhea)

26. Legionnaire's Disease: Radiographic findings
CXR findings vary; however, rapidly progressive, asymmetric fluffy alveolar infiltrates in the lower lobes are characteristic.
Pleural effusions are common, even in the absence of an obvious infiltrate.
At left, CXR shows bilateral alveolar opacities, L>R, lower lobe predominant, in a patient with legionella PNA.
Image courtesy of

27. Legionnaire's Disease: Diagnosis, Prognosis
Can check urine Legionella antigen
Only detects serotype 1, which is 70-80% of cases, but fast, and specificity >99%
Prognosis:
Untreated, mortality is 15-30%
In AIDS patients, untreated mortality is 50%!

28. Legionnaire's Disease: Treatment
Give a quinolone (levofloxacin, ciprofloxacin) or macrolide (azithromycin, clarithromycin)
One study showed a similar outcome with a quinolone vs. a macrolide, but shorter hospital stay with quinolones1
DIFFERS from normal CAP treatment in that dose is HIGHER and course is LONGER
For instance:
For Legionella: levofloxacin 750mg daily for days
For “normal” CAP: 500mg daily for 5 days
1) Blázquez Garrido Rm et al. Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides. Clin Infect Dis. 2005;40(6):800.

29. Gram-negative organisms
UNCOMMON cause of CAP
More common in patients with CAP who get admitted to the ICU (after S. pneumo, 2nd most common cause of CAP requiring ICU admission)
Gram (-) CAP organisms: Klebsiella pneumoniae, E. coli, Enterobacter, Serratia, Proteus, Pseudomonas, H flu, Acinetobacter, and others
Risk factors for Pseudomonas CAP: cystic fibrosis, bronchiectasis, and repeated steroid/antibiotic regimens in COPD patients

30. Haemophilus influenzae
H. flu CAP seen primarily in older adults and patients with underlying pulmonary disease
The H. influenzae vaccine is known as the HIB vaccine, because it covers type B only (the most common H. flu strand)
The earliest HIB vaccine was first used in the US in 1985; older patients and immigrants may never have been vaccinated.
H. flu CAP is usually from strains of H. flu not covered by the vaccine (“nontypeable H. flu”)
Gram stain: gram (-) rod
Image courtesy of textbookofbacteriology.net

31. Viral Pneumonia
In one trial1 of 107 CAP patients, 26% had a viral cause as determined by PCR.
The availability of PCR has increased diagnostic yield vs older methods like viral culture.
Influenza is most common cause of viral CAP.
Other viral causes: RSV, parainfluenza, adenovirus
1) Cesario TC. Viruses associated with pneumonia in adults. Clin Infect Dis. 2012;55(1):107.

32. “Yeast pneumonia?” This is very rare. Usually, don’t chase it
Candida is commonly seen on sputum cultures. It is a frequent colonizer; RARELY a pathogen.
Autopsy study1 of 77 patients with pneumonia and candida on BAL culture found no histological evidence of invasive candidal infection in any sample.
The few candida PNA cases are from hematogenous spread in severely immunocompromised patients: multi-nodular disease would be expected and make candida in sputum more suspicious.
If suspicion for yeasts that do causes dangerous PNA (histoplasma, blastomycosis, coccidiomycosis, cryptococcus, PCP), call the micro lab and have them speciate the yeast.
1) Kontoyiannis DP et al. Pulmonary candidiasis in patients with cancer: an autopsy study. Clin Infect Dis. 2002;34(3):400.

33. Table of contents Introduction to CAP: definitions, epidemiology
What causes CAP?
Overview of specific organisms
Risk stratification
Diagnosis of CAP
Treatment of CAP

34. Risk-stratifying severity of CAP
Severity of CAP ranges from a benign, “walking” pneumonia, to respiratory failure requiring ICU admission. How can we decide who requires admission and IV antibiotics?
Best validated “severity score” is the:
“Pneumonia Severity Index”

35. Pneumonia Severity Index (PSI)
Online calculator:
Stratifies patients into quintiles of risk for 30 day mortality based on variables including comorbidities, physical exam, lab values.
Score < 90, unlikely to need admission or IV abx. Score >90, likely needs to be admitted.

36. Validation of the PSI (…can we trust it?)
Originally published in Derived from the Pneumonia Patient Outcomes Research Team (PORT) analysis of 14,199 inpatients with CAP. 1
Validated on 50,000 patients with CAP (combination of inpatient and outpatient).2
Aujesky D, Fine MJ. The pneumonia severity index: a decade after the initial derivation and validation. Clin Infect Dis. 2008;47 Suppl 3:S133-9.
Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336(4):
1) Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med. 1997;336(4):
2) Aujesky D, Fine MJ. The pneumonia severity index: a decade after the initial derivation and validation. Clin Infect Dis. 2008;47 Suppl 3:S133-9.

37. PSI is good at identifying patients at low risk of mortality
No significant differences in 30 day mortality between derivation group (14,000 patients) and validation group of (50,000 patients).
Among 1,575 patients in the three lowest risk classes in the original PORT cohort, there were only seven deaths, of which only four were pneumonia-related.

38. Table of contents Introduction to CAP: definitions, epidemiology
What causes CAP?
Overview of specific organisms
Risk stratification
Diagnosis of CAP
Treatment of CAP

39. Which patients warrant testing for the specific etiology?
Per 2007 IDSA Guidelines:

40. More specifically… Indication Sputum Culture Blood Culture
Urine testing (Legionella or pneumococcal antigen)
Other
Outpatient No
Just treat it!
Outpatient, failure of 1st antibiotics
Yes
Look a little more
Cavitary lesions
Yes (pneumococcal)
Consider TB and fungal causes too
Alcohol abuse
No spleen
Consider
Aggressively look/treat for pneumococci
ICU patients
Endotracheal tube or BAL culture if possible
Inpatients
Per 2007 IDSA guidelines

41. Summary: testing for specific etiology
In the outpatient setting, with a low PSI score, empiric treatment is reasonable and preferred as it is low cost (no need to get sputum or blood cultures).
Rationale: In one study1 of 700+ ambulatory patients treated for CAP, empiric antibiotics were almost universally effective
Only 2.2% required hospitalization due to failure of the outpatient regimen
In inpatients and individuals with comorbidities (e.g. EtOH abuse, asplenia), diagnostic testing is usually warranted.
1) Malcolm C et al. Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting. Arch Intern Med. 2003;163(7):797

42. How good are sputum cultures anyways?
The yield varies, study to study, from <10% to 50%
Affected by need to give antibiotics in <6 hours in most Emergency Rooms
Need to get a good, deep sputum
A "good" sputum sample is one with PMNs but a low or absent number of squamous epithelial cells (SECs) on Gram stain. Best when <25 SECs per low power field
A “true” pathogen should grow in moderate or heavy amounts (colonizers often in lower amounts)

43. A good sputum culture:
A bad sputum culture:

44. Viral PCR testing
Caution is necessary in interpretation since up to 15 percent of healthy persons harbor a respiratory tract virus at any point of time.
An exception is influenza: detection of this virus usually indicates infection
Furthermore, viruses are commonly found in the nasopharynx of adults with CAP. Often the virus is not the cause of lower tract infection, but rather leads to impaired mucociliary clearance so a bacterial pathogen can infect the lower tract.

45. Testing for viral PNA: nasopharyngeal swab
This is not pleasant!!

46. Diagnosis of CAP: Imaging
Remember: an infiltrate on lung imaging is required for the diagnosis of CAP according to the 2007 IDSA guidelines.
Chest radiography is appropriate for most patients with suspected pneumonia.
CT scans have not been shown to improve outcomes in CAP  reserve CT for when suspicious of a cavity, mass, adenopathy, or a complication like empyema.

47. A brief interlude: Where is the PNA? (name the lobe)

48. Taken from excaliburmed.com

49. Right middle lobe consolidation:
Opacity obscures the right heart border (positive silhouette sign), but the right diaphragmatic border is maintained.

50. “Blossoming” pneumonia?
CASE: An 82yo F comes to the hospital febrile, hypoxic, and with acute kidney injury. The CXR is normal in the ER, but on repeat CXR after IVF, there is a left lower lobe consolidation.
This situation is often explained as follows: “a dehydrated patient with PNA can have an initial negative CXR, which then ‘blossoms’ after hydration.” Is this maxim true?

51. “Blossoming” pneumonia?
One study evaluated 2,700 suspected CAP cases with a negative CXR. Of those, 33% were admitted, and 7% of those admitted had a positive CXR within 2 days.1
So “blossoming” does happen, though it is rare.
IDSA guidelines “consider it reasonable” to empirically treat for CAP for 1-2 days with a negative CXR, then repeat CXR. If still negative, recommend looking for another cause.
1) Basi SK et al. Patients admitted to hospital with suspected pneumonia and normal chest radiographs: epidemiology, microbiology, and outcomes. Am J Med. 2004;117(5):305.

52. Table of contents Introduction to CAP: definitions, epidemiology
What causes CAP?
Overview of specific organisms
Risk stratification
Diagnosis of CAP
Treatment of CAP

53. Treatment of CAP
In the outpatient setting, with a low PSI score, empiric treatment is reasonable and preferred as it is low cost.
Recall the study1 mentioned earlier of 700 outpatients treated empirically for CAP: what percent of patients required hospitalization for failure of the empiric regimen?
1) Malcolm C et al. Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting. Arch Intern Med. 2003;163(7):797

54. Treatment of CAP
In the outpatient setting, with a low PSI score, empiric treatment is reasonable and preferred as it is low cost.
Recall the study1 mentioned earlier of 700 outpatients treated empirically for CAP: what percent of patients required hospitalization for failure of the empiric regimen?
Answer: Only 2.2%! Empiric antibiotics usually work.
1) Malcolm C et al. Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting. Arch Intern Med. 2003;163(7):797

55. IDSA CAP treatment guidelines: Outpatient pneumonia
Previously healthy, no other antibiotic exposure in last 3 months:
Macrolide (azithromycin) or doxycycline
These have gram (+) and atypical coverage, to cover the most typical bacteria (Strep pneumo, Mycoplasma, Chlamydophila pneumoniae)

56. An important caveat…
Prevalence of macrolide-resistant S. pneumoniae strains is now >25% in most parts of the United States, including at BIDMC, and resistance rates continue to increase.
Remember: what is the most common microbe causing CAP?
Though IDSA guidelines still recommend macrolides for uncomplicated CAP, some experts now recommend AGAINST empiric macrolide monotherapy where local prevalence of macrolide resistant s. pneumo is >25%. This remains controversial.
In regions with >25% macrolide-resistance strains of s. pneumo, consider instead using doxycycline or one of the regimens described on the next slide.
In a large surveillance study of 14,934 isolates of S. pneumoniae collected in the United States from 1998 through 2009, the percent of isolates susceptible to erythromycin (MIC ≤0.25 mcg/mL) decreased from 82.2 to 60.8 percent [92].

57. An important caveat…
Prevalence of macrolide-resistant S. pneumoniae strains is now >25% in most parts of the United States, including at BIDMC, and resistance rates continue to increase.
Remember: what is the most common microbe causing CAP?
Though IDSA guidelines still recommend macrolides for uncomplicated CAP, some experts now recommend AGAINST empiric macrolide monotherapy where local prevalence of macrolide resistant s. pneumo is >25%. This remains controversial.
In regions with >25% macrolide-resistance strains of s. pneumo, consider instead using doxycycline or one of the regimens described on the next slide.
Answer: S. pneumo is the most common cause of both outpatient and inpatient CAP
In a large surveillance study of 14,934 isolates of S. pneumoniae collected in the United States from 1998 through 2009, the percent of isolates susceptible to erythromycin (MIC ≤0.25 mcg/mL) decreased from 82.2 to 60.8 percent [92].

58. IDSA CAP treatment guidelines: Outpatient with underlying disease
Chronic heart, lung, liver, or kidney disease; no spleen; diabetes; EtOH abuse; other antibiotics in last 3 months
“Respiratory” fluoroquinolone (levofloxacin, moxifloxacin) (cipro doesn’t have much gram+ coverage, so will miss S. pneumo) OR
Beta-lactam (high dose amoxicillin or augmentin AND a macrolide (azithromycin, clarithromycin)
Addition of beta lactam gives better S. pneumo coverage.
The conditions at the top are risk factors for antibiotic resistance. You’re adding broader coverage (more gram negatives, better S. pneumo coverage), still focusing on Strep pneumo and atypicals

59. Given high rates of macrolide resistance, why not just give fluoroquinolones for all outpatient CAP?
There is widespread concern for increasing fluoroquinolone resistance. Prior fluoroquinolone use has been shown to be a risk factor for developing quinolone-resistant S. pneumo. 1
Despite these risks, quinolones ARE given frequently, and often inappropriately, for uncomplicated outpatient CAP:
In one report of 768 ambulatory patients with CAP, 32 percent were treated with levofloxacin; one-half of these patients did not meet the criteria for appropriate fluoroquinolone therapy. 2
Malcolm, C, Marrie, TJ. Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting. Arch Intern Med 2003; 163:797.
Vanderkooi OG, Low DE, Green K, Powis JE, Mcgeer A. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis. 2005;40(9):
) Malcolm, C, Marrie, TJ. Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting. Arch Intern Med 2003; 163:797.

60. IDSA CAP treatment guidelines: Inpatients NOT in the ICU
Take the “complicated outpatient” regimens from before, and consider making them IV
“Respiratory” fluoroquinolone (levofloxacin, moxifloxacin)[note: PO and IV equivalent] OR
Beta-lactam (Ceftriaxone, ampicillin-sulbactam [aka Unasyn] AND a macrolide (azithromycin, clarithromycin)

61. IDSA CAP treatment guidelines: ICU patients
More likely to have CA-MRSA, Legionella, and gram negative rods including Pseudomonas.
Take the “ward regimen” up a notch
(1) Beta-lactam (Ceftriaxone, ampicillin-sulbactam [aka Unasyn])
AND
(2A) Macrolide (azithromycin, clarithromycin) OR
(2B) Respiratory fluoroquinolone (levofloxacin, moxifloxacin)
*If pseudomonas suspected, add zosyn or cefepime in place of beta lactam listed under (1) above.
*If CA-MRSA suspected, add vancomycin or linezolid.

62. Duration of antibiotics for CAP
At least 5 days
7-10 days typical
Should be afebrile hours and hemodynamically stable before stopping
Longer if there are complicating features (bacteremia, empyema)

63. QUIZ YOURSELF Remember, treatment differs for certain organisms:
Microbe: Tx:
Legionella ____________
CA-MRSA ____________
Pseudomonas ____________
(Answers appear on the next slide)

64. QUIZ YOURSELF Remember, treatment differs for certain organisms:
Microbe: Tx:
Legionella Higher dose, longer course, of quinolone or macrolide
CA-MRSA Add vanc or linezolid (dapto is inactivated by surfactant)
Pseudomonas If high risk for pseudomonas, double cover until sensitivities return (e.g. quinolones, tobramycin; cefepime; ceftazadime; zosyn; aztreonam)

65. Expected response to treatment
With appropriate abx, patient should be improving within hours
>72 hours is definition of “non-responder”
However, in one study1 87% of inpatients with CAP had persistence of at least one PNA symptom (fatigue, cough with or without sputum production, dyspnea, chest pain) at 30 days. So tell your patients it may take a while for them to feel completely better.
1) Menéndez R et al. Risk factors of treatment failure in community acquired pneumonia: implications for disease outcome. Thorax. 2004;59(11):960.

66. Expected CXR response to treatment
The CXR findings lag behind the clinical picture for several weeks
In one study1:
Day 1: 100% had clinical findings, 100% had CXR findings
Day 7: 44% with clinical findings, 75% had CXR findings
Day 28: 22% still symptomatic, 47% still have CXR findings
Patients with persistent CXR findings had no different clinical outcome than those with early resolution of CXR findings
1) Bruns AH et al. Clin Infect Dis. 2007;45(8):983. Patterns of resolution of chest radiograph abnormalities in adults hospitalized with severe community-acquired pneumonia.

67. Important adjuvants to antibiotics
Influenza vaccine
Pneumococcal vaccine
Smoking cessation

68. Pneumococcal vaccines (PPSV23, PCV13)
Most studies do NOT show a decrease in pneumonia
But they DO show a decrease in invasive strep pneumo e.g. bacteremia and meningitis (Odds Ratio 0.26)
New guidelines as of 2014 for adults age 65 and older:
Adults age 65 and older should receive PCV13 followed by PPSV23 6 to 12 months later.
In those who have already received PPSV23, at least one year should elapse before they are given PCV13.
Guidelines differ for patients with comorbidities that predispose to pneumococcal infection; for specifics, see:

69. Time to practice…

70. Question #1
A 45 year old man with no PMH presents to your primary care office with two days of fever, malaise, and myalgias. A nasal swab is positive for influenza A. The patient is treated at home with supportive care. Over the next two days, he appears to be clinically improving, with resolution of his fever. However, after being afebrile for 48 hours, he experiences fever, productive cough, and shortness of breath. He presents to the emergency department.
Initial vital signs are: T 102 F, BP 120/75, HR 95, RR 22, O2 saturation 90% on RA. Physical exam reveals wet crackles in the lower lung fields bilaterally. In addition to further diagnostic studies, what is an appropriate empiric antibiotic regimen for this patient?
A) No antibiotics indicated at this time.
B) IV levofloxacin
C) Ceftriaxone + azithromycin
D) Piperacillin-Tazobactam
E) Ceftriaxone, azithromycin, and vancomycin

71. Question #1
A 45 year old man with no PMH presents to your primary care office with two days of fever, malaise, and myalgias. A nasal swab is positive for influenza A. The patient is treated at home with supportive care. Over the next two days, he appears to be clinically improving, with resolution of his fever. However, after being afebrile for 48 hours, he experiences fever, productive cough, and shortness of breath. He presents to the emergency department.
Initial vital signs are: T 102 F, BP 120/75, HR 95, RR 22, O2 saturation 90% on RA. Physical exam reveals wet crackles in the lower lung fields bilaterally. In addition to further diagnostic studies, what is an appropriate empiric antibiotic regimen for this patient?
A) No antibiotics indicated at this time.
B) IV levofloxacin
C) Ceftriaxone + azithromycin
D) Piperacillin-Tazobactam
E) Ceftriaxone, azithromycin, and vancomycin
[see next slide for explanation]

72. Question #1 Explanation:
This young, healthy patient presents with worsening fever and respiratory symptoms after initial improvement of the sequelae of influenza. This progression of symptoms is characteristic of secondary bacterial pneumonia, an important complication of influenza. Given his decreased spO2 and physical exam findings, he will likely require hospitalization. In many situations, choices B and C represent reasonable empiric inpatient therapy for CAP. In this case, however, the patient is at risk of post-influenza CA-MRSA pneumonia, which has been shown to cause severe necrotizing pneumonia in young, otherwise healthy patients after flu infection. In one case series of patients diagnosed with post-influenza CA-MRSA pneumonia during the flu season, the median age was 16 years and 44% had no significant comorbidities. 1 Given the high mortality associated with CA-MRSA pneumonia, empiric treatment with vancomycin is warranted.
1) Kallen AJ, Brunkard J, Moore Z, et al. Staphylococcus aureus community-acquired pneumonia during the 2006 to 2007 influenza season. Ann Emerg Med. 2009;53(3):

73. Question #2
A 36 year old woman with no past medical history comes to her PCP complaining of 5 days of low-grade fevers, malaise, fatigue, headache, and non-productive cough. She denies sick contacts and says she received a flu shot this year.
Vital signs are T 100.1, HR 75, BP 118/76, RR 16, SpO2 100% on RA. She is well-appearing, and physical exam reveals faint crackles in the left lower lung field. Exam is otherwise normal. A chest X ray shows patchy areas of consolidation in the left lower lobe.
What is the most appropriate next step?
A) Sputum culture and gram stain
B) Sputum culture, gram stain, blood culture, and CBC
C) Start azithromycin monotherapy
D) Start levofloxacin

74. Question #2
A 36 year old woman with no past medical history comes to her PCP complaining of 5 days of low-grade fevers, malaise, fatigue, headache, and non-productive cough. She denies sick contacts and says she received a flu shot this year.
Vital signs are T 100.1, HR 75, BP 118/76, RR 16, SpO2 100% on RA. She is well-appearing, and physical exam reveals faint crackles in the left lower lung field. Exam is otherwise normal. A chest X ray shows patchy areas of consolidation in the left lower lobe.
What is the most appropriate next step?
A) Sputum culture and gram stain
B) Sputum culture, gram stain, blood culture, and CBC
C) Start azithromycin monotherapy
D) Start levofloxacin
[see next slide for explanation]

75. Question #2
EXPLANATION: This question describes a young, otherwise healthy woman with no known comorbidities who presents with 5 days of fever, malaise, and non-productive cough. Her pulmonary exam and chest x ray are suggestive of community acquired bacterial pneumonia. While clinical exam cannot reliably distinguish between typical (e.g. pneumococcal) pneumonia and atypical (e.g. mycoplasma or chlamydia) pneumonia, certain factors in this patient’s story raise suspicion for atypical pneumonia: onset of symptoms over 5 days (vs 1-2 days in typical bacterial PNA), non-productive cough (vs mucopurulent sputum in typical bacterial PNA), and the patient’s overall well appearance. The 2007 IDSA/ATS consensus guidelines suggest that routine tests to identify an etiology for CAP are optional for patients who are otherwise healthy and do not require hospitalization. Thus A and B are unnecessary for this patient, and empiric treatment is likely to be successful. (Remember, too, that the atypical bacteria mycoplasma and chlamydia are not visible). Azithromycin monotherapy (C) is likely sufficient coverage for the most common causes of outpatient PNA – mycoplasma, chlamydia, and strep pneumo. We are not told the local prevalence of macrolide resistant strep pneumo, but given this patient’s general good health, stable vital signs, and overall well appearance, broadening coverage to levofloxin (D) would be inappropriate.

76. Question #3
A 72 year old man with a history of hypertension and congestive heart failure (most recent EF 40%) comes to the Emergency Department complaining of 2 days of shortness of breath, productive cough, and a fever to His vital signs are as follows: temperature 35.6 degrees Celsius, heart rate 110, blood pressure 115/75, respiratory rate 35, and oxygen saturation 93% on room air. Physical exam is notable for an alert, oriented patient with coarse crackles in the left lower lung field.  
Laboratory results include the following:
WBC 3,000, Hgb 11.9, Platelets 150,000
Na 137, K 4.0, BUN 45, Cr 1.5
A chest x ray reveals an opacity in the left lower lobe and small left-sided pleural effusion.
What is the most appropriate disposition for this patient?
A) Discharge home on appropriate antibiotics
B) Monitor in the emergency department for 24 hours
C) Admit to general medicine service
D) Directly admit to ICU

77. Question #3
A 72 year old man with a history of hypertension and congestive heart failure (most recent EF 40%) comes to the Emergency Department complaining of 2 days of shortness of breath, productive cough, and a fever to His vital signs are as follows: temperature 35.6 degrees Celsius, heart rate 110, blood pressure 115/75, respiratory rate 35, and oxygen saturation 93% on room air. Physical exam is notable for an alert, oriented patient with coarse crackles in the left lower lung field.  
Laboratory results include the following:
WBC 3,000, Hgb 11.9, Platelets 150,000
Na 137, K 4.0, BUN 45, Cr 1.5
A chest x ray reveals an opacity in the left lower lobe and small left-sided pleural effusion.
What is the most appropriate disposition for this patient?
A) Discharge home on appropriate antibiotics
B) Monitor in the emergency department for 24 hours
C) Admit to general medicine service
D) Directly admit to ICU
[See next slide for explanation]

78. Question #3
EXPLANATION: This patient with a history of CHF presents with community acquired pneumonia associated with a number of concerning signs and symptoms: temperature >40 degrees, tachycardia, tachypnea, leukopenia, and uremia. Using the Pneumonia Severity Index and the given information, the patient’s mortality risk is 26%. Using the CURB-65 criteria, the patient meets 3/5 criteria, corresponding to a 14% estimated 30-day mortality. Given the high risk of mortality, he should be admitted to the hospital for further management, so answers A and B are incorrect. Though the patient is currently saturating well on room air, ICU admission (answer D) is warranted. The 2007 IDSA guidelines suggest a number of major and minor criteria for ICU admission in patients with CAP. Two major criteria (requirement for invasive ventilation and septic shock requiring vasopressors) are considered absolute indications for ICU admission. Minor criteria include leukopenia, uremia, hypothermia, multilobar infiltrates, P/F ratio <250, RR>30, confusion, hypotension, and thrombocytopenia. In the presence of 3 or more minor criteria, the guidelines recommend ICU admission. This patient meets 4 minor criteria – hypothermia, uremia, leukopenia, and tachypnea – and should be admitted to the ICU.

79. Congratulations! Please take the post-module quiz here