#76: Pneumonia Pearls with Dr Robert Centor

January 1, 2018 | By Justin Berk

Conquer community acquired pneumonia and avoid misdiagnosis with tips from Dr. Robert Centor, Professor Emeritus University of Alabama and newly appointed Chair of Medicine at Kashlak Memorial Hospital. We discuss diagnosis, misdiagnosis, procalcitonin, steroids for severe pneumonia, pneumonia severity index versus CURB-65, and how to determine antibiotic choice and duration. Special thanks to Correspondents Neela Bhajandas (cohost), Justin Berk and Bryan Brown who all contributed several articles, resources, and questions to prep for this show.

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Case from Kashlak Memorial: 38 year old male, active smoker with bipolar disorder (on olanzapine 20 mg hs, citalopram 40 mg), obesity (BMI 31), HTN (on lisinopril/HCTZ) presents to the ED with 7 days of progressive cough with scant sputum production, dyspnea on exertion, and wheezing. The ED called me to evaluate him for admission.

Clinical Pearls:

1. “…being called from the emergency department for the diagnosis of community acquired pneumonia is a chance for us to think.”…”let’s first assume that it’s NOT that, and then try to convince ourselves that it is pneumonia”. -Dr Centor
2. Rules for early antibiotic administration prompted attempts by the ED to diagnose pneumonia with higher sensitivity. This led to lower specificity, increased number of false positives and antibiotic (abx) overuse. -Dr Centor
3. Diagnostic criteria for pneumonia: [Welker Arch Int Med 2008] Presence of all 3 of the following criteria:
   1. new or increasing infiltrate by chest x ray (CXR) or chest CT
   2. plus, temp >38.0°C or <35.1°C or a WBC > 10/μL or < 4.5/μL, or bands > 15%;
   3. plus, 2 of: cough, dyspnea, pleuritic chest pain, tachypnea w/RR > 30/min, hypoxia <90% or PaO2 < 60 mmHg, auscultatory findings of pneumonia, including: rales, dullness of percussion, bronchial breath sounds, or egophony; or newly required mechanical ventilation by either intubation or noninvasive ventilation.
4. Community acquired pneumonia (CAP) definition: Pneumonia caused by any of various organisms that does not meet diagnostic criteria for HAP or VAP (see below).
5. Hospital acquired pneumonia (HAP) definition: occurs 48 hours or more after hospital admission and wasn’t incubating at the time of admission. Ventilator associated pneumonia (VAP) develops more than 48 to 72 hours after endotracheal intubation (IDSA HAP and VAP g/l 2016, and  UpToDate.com).
6. Healthcare associated pneumonia (HCAP) definition: Don’t use this term anymore! Treat these patients as CAP and assess/treat if multidrug resistance risk factors present (see below for MRSA and Pseudomonas).
7. Assess MRSA risk factors and treat for MRSA if: GPCs in clusters on sputum gram stain, ESRD, IVDU, recent influenza, necrotizing or cavitary pneumonia (IDSA CAP g/l 2007)
8. Check MRSA swab and de-escalate if negative (https://www.ncbi.nlm.nih.gov/pubmed/27591173)
9. Assess Pseudomonas risk factors and treat if: GNR on sputum gram stain, COPD with frequent exposure to steroids/antibiotics, structural lung disease (e.g. bronchiectasis), “prior abx exposure”, alcoholism [IDSA CAP g/l 2007].
10. Assess Drug resistant Streptococcus pneumoniae (DRSP) risk factors and treat if: Local Strep resistance to macrolide >25%; age >65; comorbidities; alcoholism; exposure to kids in daycare; Beta lactam, fluoroquinolone (FQ), or macrolide abx use in past 3-6 months. (UptoDate)
11. “Comorbidities” per [IDSA CAP g/l 2007]: Chronic heart, lung, liver, renal disease, diabetes, cancer, alcoholism, asplenia, immunosuppression, abx exposure in past 3 mo.
12. Pneumonia may “blossom” on repeat CXR after initial negative study if initial BUN elevated or if higher fluid volume administered in first 48 hours (RB Hash J Fam Pract 2000)
13. Illness script: Expected patient presentation (history, labs, exam, signs/symptoms) for a given problem e.g. pneumonia.
14. Problem representation: A brief summary of what is wrong with the patient.
15. Diagnosis/Misdiagnosis: A patient’s “illness script” must match their “problem representation”. If not, then clinician must consider other diagnoses through analytical thinking and differential diagnosis. -Dr Robert Centor (see this article)
16. Pneumonia scoring systems: Useful to estimate mortality risk. Low risk patients can be sent home. High risk patients need admission. Plan MUST take into account the patient’s social support and ability to comply with treatment.
17. Pneumonia severity index (PSI): Calculator found here. Outpatient care for scores I-II. Score of III is borderline. Inpatient care for scores IV-V (IDSA CAP g/l 2007). Calculation requires blood gas, basic metabolic panel, blood count, oxygen sat, CXR. Less cumbersome to calculate using smartphone. Dr Centor recommends PSI over CURB-65.
18. CURB-65: Confusion, uremia (BUN >20), RR ≥30, Systolic BP <90, Diastolic BP ≤60, Age >65. Inpatient care if score  ≥2. Severe pneumonia if score 3-5 (IDSA CAP g/l 2007).
19. Additional testing and labs: Consider checking blood cultures, sputum cultures (Dr Centor is not a fan), legionella urinary Ag, pneumococcal urinary Ag. See Table 3 in IDSA pocket card for details.
20. Procalcitonin (PCT): A calcitonin-related gene product. PCT production increased w/bacterial infections and decreased w/viral infection. PCT falls rapidly during recovery/tx of bacterial infection. Consider starting abx if >0.25 mcg/L in outpatients or ED, and >0.5 mcg/L in ICU. Cut-offs for starting, and stopping abx differ by study and assay used. Only helpful if rapid results available (i.e. within hours). May decrease 30-day mortality, abx exposure, abx side effects (Scheutz P. Lancet Infectious Diseases 2017). Outpatient management with PCT is cost-effective. Overall, use of PCT overall still controversial among ID docs.
21. Antibiotic choice outpatient without comorbidities: Macrolide or doxycycline. Modify as needed if risk factors for MRSA, pseudomonas, DRSP (see above).
22. Antibiotic choice outpatient with comorbidities: Monotherapy with respiratory FQ, or Beta lactam (high dose amoxicillin or high dose amoxicillin-clavulanic acid or 2nd/3rd gen. cephalosporin) plus macrolide (or doxycycline). Modify as needed if risk factors for MRSA, pseudomonas, DRSP (see above).
23. Antibiotic duration: Should see improvement within first 48-72 hours on tx. Otherwise, one must question the diagnosis of pneumonia. It’s okay to stop abx at 5 days if markers of clinically instability are absent (e.g. no oxygen requirement above patient’s baseline, afebrile for 48-72 hours, HR <100, RR <24, SBP >90) (IDSA CAP g/l 2007).
24. Doxycycline has decreased risk for C diff (SB Doenberg Clin Inf Dis 2012, ID Week 2017). Also, it does not cause QTc prolongation.
25. QTc prolongation: “The more the merrier”. Thus, using a higher number of QTc prolonging agents increases the risk for torsades de pointe. Be careful!
26. Corticosteroids in severe pneumonia: Treats a hypothesized “critical illness related corticosteroid insufficiency” aka relative adrenal insufficiency. Not currently recommended for routine use in pneumonia, but may be considered if severe.
27. Evidence for steroids in severe pneumonia: Meta-analysis by Siemieniuk et al Annals of IM 2015 showed decreased length of hospital stay, need for mechanical ventilation, ARDS, and time to clinical stability, especially in severe pneumonia. Meta-analysis by J. Bi et al PLoS One 2016 found decreased relative risk all-cause mortality, ARDS, and need for mechanical ventilation in patients with severe CAP, but studies were small with wide confidence intervals.

Goal: Listeners will utilize an evidence based approach to prognosis, diagnosis, and management of community acquired pneumonia

Learning objectives:
After listening to this episode listeners will…

1. Define community acquired pneumonia
2. Recall why pneumonia is commonly misdiagnosed
3. Utilize illness scripts and problem representation to evaluate diagnostic accuracy
4. Utilize available risk scores to stratify patients with CAP and determine appropriate level of care
5. Evaluate efficacy of steroids for severe CAP
6. Utilize procalcitonin to guide antimicrobial use and duration
7. Choose the appropriate antibiotics based on risk factors and setting
8. Determine appropriate antibiotic duration

Disclosures: Dr Centor, The Curbsiders, and Dr Bhajandas report no relevant financial disclosures.

Time Stamps

• 00:00 Intro
• 02:38 Brief bio for Dr Centor
• 04:22 Picks of the week with Dr Centor
• 11:27 Clinical case of suspected pneumonia
• 12:30 Brief history of community acquired pneumonia
• 14:40 Misdiagnosis rates are high
• 16:18 Defining diagnostic criteria for pneumonia
• 18:50 Chest x rays and pneumonia
• 22:18 Illness scripts teaching about pneumonia
• 23:41 Ubiquitous misunderstanding of pneumonia definition
• 25:26 History and physical exam tips from Dr Centor
• 27:19 Further testing for pneumonia, PSI, CURB-65
• 32:50 Procalcitonin discussed
• 38:10 Antibiotic choice discussed with Dr Bhajandas
• 41:15 Safety considerations for various antibiotics
• 43:38 Use of high dose amoxicillin
• 44:45 Dr Centor’s antibiotic preferences, and some thoughts on blood and sputum cultures
• 46:55 Dangers of fluoroquinolones
• 48:25 Antibiotic duration
• 51:40 HCAP is no longer a thing and how to assess risk for drug resistant organisms
• 55:42 Corticosteroids for pneumonia
• 60:25 Inpatient antibiotic choices
• 62:00 Dr Centor’s take home points
• 62:45 Dr Centor becomes Chair of Kashlak Memorial
• 65:38 Outro

Links from the show:

1. Orangetheory Fitness Interval Training
2. Good Time (film) by Safdie Brothers
3. Lexi Comp App embedded clinical tools “Pharmacists secret weapon” -Neela Bhajandas
4. How to Figure Out the Length of Antibiotic Duration by Dr Paul Sax on NEJM HIV and ID Observations Blog.
5. Welker et al. Antibiotic timing and errors in diagnosing pneumonia. Arch Intern Med. 2008 Feb 25;168(4):351-6. (FREE abstract)
6. Judith L Bowen article from NEJM 2006 on Clinical Reasoning (Free PDF)
7. Article by Dr Robert Centor on Diagnostic Error in Pneumonia Free
8. Hagaman JT1, Rouan GW, Shipley RT, Panos RJ. Admission chest radiograph lacks sensitivity in the diagnosis of community-acquired pneumonia. Am J Med Sci. 2009 Apr;337(4):236-40. doi: 10.1097/MAJ.0b013e31818ad805.
9. Scheutz P. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infectious Diseases 2017 (Free Abstract)
10. Pneumonia Severity Index Calculator by Dr Michael Fine on MDCalc
11. Ane Uranga, Pedro P. España, Amaia Bilbao, Jose María Quintana, Ignacio Arriaga, Maider Intxausti, Jose Luis Lobo, Laura Tomás, Jesus Camino, Juan Nuñez, Alberto Capelastegui. Duration of Antibiotic Treatment in Community-Acquired Pneumonia A Multicenter Randomized Clinical Trial. JAMA Intern Med. 2016;176(9):1257–1265. doi:10.1001/jamainternmed.2016.3633 (FREE)
12. IDSA Pocket Card for CAP (FREE) http://eguideline.guidelinecentral.com/i/53989-community-acquired-pneumonia/1?m4=
13. IDSA PDF for CAP guidelines 2007 (FREE)
14. MRSA swab has >98% NPV in pneumonia https://www.ncbi.nlm.nih.gov/pubmed/27591173
15. HCAP is no longer a thing Treatment of hospital-acquired and ventilator-associated pneumonia in adults by T. File et al UpToDate.com
16. FDA Warning for Fluoroquinolone antibiotics https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm
17. Pneumonia may blossom even after initial negative CXR RB Hash. J Fam Pract. 2000 September;49(9):833-837
18. Efficacy and Safety of Adjunctive Corticosteroids Therapy for Severe Community-Acquired Pneumonia in Adults: An Updated Systematic Review and Meta-Analysis. Bi J, Yang J, Wang Y, Yao C, Mei J, Liu Y, Cao J, Lu Y. PLoS One. 2016 Nov 15;11(11):e0165942. doi: 10.1371/journal.pone.0165942. eCollection 2016. Review. PMID: 27846240 (FREE!)
19. Reed A.C. Siemieniuk, Maureen O. Meade, Pablo Alonso-Coello, Matthias Briel, Nathan Evaniew, Manya Prasad, et al. Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015;163:519–528. doi: 10.7326/M15-0715

Recommended reading and resources

1. Does this patient have community-acquired pneumonia? Diagnosing pneumonia by history and physical examination. Metlay JP et al. JAMA. (1997)
2. Clinical practice. Community-acquired pneumonia. Wunderink RG, Waterer GW. N Engl J Med. 2014 Feb 6;370(6):543-51. doi: 10.1056/NEJMcp1214869. Review. No abstract available. PMID: 24499212
3. Community-acquired pneumonia. Remington LT, Sligl WI. Curr Opin Pulm Med. 2014 May;20(3):215-24. doi: 10.1097/MCP.0000000000000052. Review. PMID: 24614242
4. Advances in the causes and management of community acquired pneumonia in adults. Wunderink RG, Waterer G. BMJ. 2017 Jul 10;358:j2471. doi: 10.1136/bmj.j2471. Review. PMID: 28694251
5. Procalcitonin for selecting the antibiotic regimen in outpatients with low-risk community-acquired pneumonia using a rapid point-of-care testing: A single-arm clinical trial. Masiá M, Padilla S, Ortiz de la Tabla V, González M, Bas C, Gutiérrez F. PLoS One. 2017 Apr 20;12(4):e0175634. doi: 10.1371/journal.pone.0175634. eCollection 2017. PMID: 28426811 (FREE!)
6. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Int Med 2011
7. Efficacy and Safety of Corticosteroids for Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis. Wan YD, Sun TW, Liu ZQ, Zhang SG, Wang LX, Kan QC. Chest. 2016 Jan;149(1):209-19. doi: 10.1378/chest.15-1733. Epub 2016 Jan 6. Review. PMID: 26501852
8. Pneumonia YouTube videos with awesome animations from Yale created by our correspondent Dr Bryan Brown First part- the “five minute assessment”; 2nd part- Diagnosis; 3rd part- Management.