Pneumonia - Infectious Disease learning modules - Home

Pneumonia - Infectious Disease learning modules - Home

Community Acquired Pneumonia A NDY HALE, MD M O L LY B R E T T, M D Welcome to the module on Community Acquired Pneumonia!! Please take this brief pre-module quiz https://goo.gl/forms/rTStTb4wNvULzdjq2 Table of contents 1. 2. 3. 4. 5. 6. Introduction to CAP: definitions, epidemiology

What causes CAP? Overview of specific organisms Risk stratification Diagnosis of CAP Treatment of CAP 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. 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 1 2004;39(11):1642-50.. 2) File TM Jr, Marrie TJ. Burden of community-acquired pneumonia in North American adults. Postgrad Med. Mar

2010;122(2):130-41. 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 Kartageners, cystic fibrosis Altered lung anatomy

Lung cancer, bronchiectasis, obstructions Immunocompromised Table of contents 1. 2. 3. 4. 5. 6. Introduction to CAP: definitions, epidemiology What causes CAP? Overview of specific organisms Risk stratification Diagnosis of CAP Treatment of CAP

What causes CAP? There are >100 organisms, but those below are most common. 1, 2, 3. Organism Unknown Streptococcus pneumoniae Mycoplasma We dont pneumoniae know most Chlamydophila of the time! pneumoniae Identified virus Haemophilus influenzae Legionella pneumophila Staph. aureus Overall rates 51%

17% Outpatient CAP Inpatient CAP 54% 60% 10% 18% 10% 12% 2% 9% 12% 2%

5% 5% 5% 5% 5% 5% 2% 1% 4% 1% 1% 4%

1) Marrie TJ, et al. Etiology of community-acquired pneumonia treated in an ambulatory setting. Resp Medicine 2005; 99:60. 2) Cilniz 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. How often is an organism isolated? RARELY! ~10% But thats OK. Empiric therapy usually works (as we will get to). Its important to know what organisms are most common so that we can choose APPROPRIATE empiric therapy, as it varies by patient and setting. Outpatient CAP: atypicals, s. pneumo Organism

Overall rates Outpatient CAP Inpatient CAP Unknown 51% 54% 60% Streptococcus pneumoniae 17%

10% 18% Mycoplasma pneumoniae 10% 12% 2% Chlamydophila pneumoniae 9% 12%

2% Identified virus 5% 5% 5% Haemophilus influenzae 5% 5% 5% Legionella

pneumophila 2% 1% 4% Staph. aureus 1% 1% 4% 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) Cilniz 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. 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 10% 12%

2% Chlamydophila pneumoniae 9% 12% 2% Identified virus 5% 5% 5% Haemophilus

influenzae 5% 5% 5% Legionella pneumophila 2% 1% 4% Staph. aureus 1%

1% 4% 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) Cilniz 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. What causes CAP? Organism Overall rates Outpatient CAP Inpatient CAP

Unknown 51% 54% 60% Streptococcus pneumoniae 17% 10% 18% Mycoplasma pneumoniae

10% 12% 2% Chlamydophila pneumoniae 9% 12% 2% Identified virus 5% 5%

5% Haemophilus influenzae 5% 5% 5% Legionella pneumophila 2% 1% 4%

Staph. aureus 1% 1% 4% 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) Cilniz 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. What causes CAP? Lets go through a few specific bacteria, and talk about unique features.

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 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. 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, 2003-04 influenza season. Emerg Infect Dis. 2006;12(6):894. CA-MRSA CAP: Clinical and pathologic manifestations CA-MRSA gram stain Gram (+) cocci in clusters.

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

CA-MRSA necrotizing PNA on CT Quiz yourself Typicallyanswer: presents as a severe Strep pneumo necrotizing appears pneumonia on gramwith stain as gram multiple positive infiltrates cocci inor pairs cavities and on short chains,

CXR and whereas CT. staph aureus, seen above, classically appears as GPCs in clusters. Mycoplasma pneumoniae Mycoplasma are the smallest organisms that can survive alone in nature (not visible on gram stain!) Hard to culture, so wont 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 www.uptodate.com Mycoplasma pneumoniae Mycoplasma are the smallest organisms that can survive alone in nature (not visible on gram stain!) Hard to culture, so wont 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 www.uptodate.com 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 www.uptodate.com 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 Opsonization by complement proteins

Intravascular hemolysis Clearance in reticuloendothelial system (extravascular) 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. 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 www.significancemagazine.org 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 (Fagets sign) Hyponatremia Mild LFT abnormalities GI symptoms (especially diarrhea) 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 www.radiopaedia.org Legionnaire's Disease: Diagnosis, Prognosis Diagnosis: 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%!

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 10-14 days

For normal CAP: 500mg daily for 5 days 1) Blzquez Garrido Rm et al. Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides. Clin Infect Dis. 2005;40(6):800. 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 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 Gram stain: gram (-) rod may never have been vaccinated. H. flu CAP is usually from strains of H. flu not covered by the vaccine (nontypeable H. flu) Image courtesy of textbookofbacteriology.net 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. Yeast pneumonia? This is very rare. Usually, dont 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. Table of contents 1. 2. 3. 4. 5. 6. Introduction to CAP: definitions, epidemiology What causes CAP? Overview of specific organisms Risk stratification Diagnosis of CAP

Treatment of CAP 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 Pneumonia Severity Index (PSI) Online calculator: http://pda.ahrq.gov/clinic/psi/psicalc.asp 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. Validation of the PSI (can we trust it?) Originally published in 1997. 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 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):243-50. 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. 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. Table of contents 1. 2. 3. 4. 5. 6. Introduction to CAP: definitions, epidemiology

What causes CAP? Overview of specific organisms Risk stratification Diagnosis of CAP Treatment of CAP Which patients warrant testing for the specific etiology? Per 2007 IDSA Guidelines: More specifically Indication Sputum Culture Blood Culture Urine testing (Legionella Other or pneumococcal

antigen) Outpatient No No No Just treat it! Outpatient, failure of 1st antibiotics Yes No

Yes Look a little more Cavitary lesions Yes Yes Yes (pneumococcal) Consider TB and fungal causes too Alcohol abuse Yes

Yes Yes No spleen Consider Yes Yes (pneumococcal) ICU patients Yes Yes Yes

Inpatients Yes Yes Consider Aggressively look/treat for pneumococci Endotracheal tube or BAL culture if possible Per 2007 IDSA guidelines 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 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) A good sputum culture: A bad sputum culture: 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. Testing for viral PNA: nasopharyngeal swab This is not pleasant!! 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.

A brief interlude: Where is the PNA? (name the lobe) Taken from excaliburmed.com Right middle lobe consolidation: Opacity obscures the right heart border (positive silhouette sign), but the right diaphragmatic border is maintained. 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? 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. Table of contents 1. 2. 3. 4. 5. 6.

Introduction to CAP: definitions, epidemiology What causes CAP? Overview of specific organisms Risk stratification Diagnosis of CAP Treatment of CAP 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 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 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) 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. 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 for cause of Answer: S.recommend pneumo is themacrolides most common both outpatient and inpatient CAP AGAINST uncomplicated CAP, some experts

now recommend 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. 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 doesnt 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. Youre adding broader coverage (more gram negatives, better S. pneumo coverage), still focusing on Strep pneumo and atypicals 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 1) Vanderkooi OG, Low DE, Green K, Powis JE, Mcgeer A. Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis. 2005;40(9):1288-97. 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. 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) 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. Duration of antibiotics for CAP At least 5 days 7-10 days typical Should be afebrile 48-72 hours and hemodynamically

stable before stopping Longer if there are complicating features (bacteremia, empyema) QUIZ YOURSELF Remember, treatment differs for certain organisms: Microbe: Tx: Legionella ____________ CA-MRSA ____________ Pseudomonas ____________ (Answers appear on the next slide) QUIZ YOURSELF Remember, treatment differs for certain organisms:

Microbe: Tx: Legionella Higher dose, longer course, of macrolide CA-MRSA Add vanc or linezolid (dapto is quinolone or inactivated by surfactant) Pseudomonas If high risk for pseudomonas, double cover until sensitivities return (e.g. quinolones, tobramycin; cefepime; ceftazadime; zosyn; aztreonam) Expected response to treatment With appropriate abx, patient should be improving within 48-72 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) Menndez R et al. Risk factors of treatment failure in community acquired pneumonia: implications for disease outcome. Thorax. 2004;59(11):960. 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. Important adjuvants to antibiotics Influenza vaccine Pneumococcal vaccine Smoking cessation 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:www.cdc.gov /vaccines/hcp/acip-recs/vacc-specific/pneumo.html Time to practice 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 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] 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 2006-2007 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):358-65. Question #2 A 36 year old woman with no past medical history comes to her PCP complaining of 5 days of lowgrade 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) B) C) D) Sputum culture and gram stain Sputum culture, gram stain, blood culture, and CBC

Start azithromycin monotherapy Start levofloxacin Question #2 A 36 year old woman with no past medical history comes to her PCP complaining of 5 days of lowgrade 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) B) C) D) Sputum culture and gram stain Sputum culture, gram stain, blood culture, and CBC Start azithromycin monotherapy Start levofloxacin

[see next slide for explanation] 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 patients 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 patients 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 patients general good health, stable vital signs, and overall well appearance, broadening coverage to levofloxin (D) would be inappropriate.

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 101. 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 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 101. 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] 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 patients 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. Congratulations! Please take the post-module quiz here https://goo.gl/forms/blnHGMPsSGjoPqpi1

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