Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) Pandemic

Ideas and Opinions7 May 2020Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) PandemicFREEJoshua P. Metlay, MD, PhD and Grant W. Waterer, MB, BS, PhDJoshua P. Metlay, MD, PhDMassachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (J.P.M.) and Grant W. Waterer, MB, BS, PhDRoyal Perth Hospital and University of Western Australia, Perth, Australia (G.W.W.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-2189 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The rapidly escalating coronavirus disease 2019 (COVID-19) pandemic has focused attention on the diagnosis and treatment of patients with acute respiratory infection in an unprecedented manner. Although most of the lung injury patients have is believed to be caused by the virus, concern over bacterial co-infection also informs current treatment approaches for patients with COVID-19–related pneumonia. As the co-chairs of the recently released American Thoracic Society and Infectious Diseases Society of America Guideline for Treatment of Adults with Community-Acquired Pneumonia (CAP) (1), we offer our interpretation of the guideline as it applies to the management of patients with COVID-19 (Table).Table. Principles for Management of Pneumonia in Patients With COVID-191. Empirical coverage for bacterial pathogens is recommended in patients with CAP without confirmed COVID-19 but is not required in all patients with confirmed COVID-19–related pneumonia.Community-acquired pneumonia is diagnosed in patients with signs and symptoms of respiratory infection (especially cough, sputum production, and fever) and radiographic evidence of lung involvement. The cause of CAP includes a range of bacteria and viruses, and with the introduction of the pneumococcal conjugate vaccine, viruses are an increasingly frequent cause (2). Despite this trend, the new guideline continues to emphasize prompt antibacterial drug therapy for all patients diagnosed with CAP. Antibacterial therapy continues to be featured so prominently in CAP guidelines because before the COVID-19 pandemic, bacterial causes of CAP were associated with the highest mortality and empirical antibacterial therapy is proven to be effective and save lives.Unfortunately, the classic microbiological diagnostic tests for CAP, sputum and blood cultures, fail to reveal a definitive pathogen in many cases (3), and although the identification of a specific pathogen can help narrow treatment decisions, the delay in obtaining a result leads to the need for initial empirical coverage, which is active against the common bacterial pathogens.Recent studies have highlighted that findings of pulmonary involvement on chest imaging in patients with confirmed COVID-19 are common, including lobar consolidation, ground glass opacities, and reticular infiltrates (4). One series estimated that 59% of hospitalized patients have abnormalities on initial chest radiography, which is consistent with pneumonia, and 86% have abnormalities on chest computed tomography (5). A largely untested hypothesis is that most of these patients with radiographic abnormalities likely have isolated severe acute respiratory syndrome coronavirus 2 infection in the lung without any additional pathogen. However, a recent case series reported that serologic evidence of co-infection with bacterial pathogens (including chlamydia) was not uncommon among fatal cases of COVID-19 pneumonia (6).2. Although data are limited, it is likely that the relevant bacterial pathogens in patients with COVID-19 and pneumonia are the same as in previous patients with CAP and therefore empirical antibiotic recommendations should be the same.The bacterial pathogens responsible for CAP are reflective of the bacteria that often colonize the upper airway and opportunistically infect the lung during a respiratory illness. Therefore, we believe the same range of pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, and Staphylococcus aureus, should be considered in patients with COVID-19–related pneumonia. For low-risk inpatients (typically those on the general medical floors), the guideline recommends a β-lactam (for example, ampicillin–sulbactam, ceftriaxone, or cefotaxime) plus either a macrolide (azithromycin or clarithromycin) or doxycycline as combination therapies or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) as monotherapy. For high-risk inpatients (typically those in the intensive care unit), the guideline recommends a β-lactam plus macrolide or β-lactam plus fluoroquinolone. We believe these same recommendations apply to patients with COVID-19.3. Testing for bacterial pathogens with sputum and blood cultures is most useful when there is concern for multidrug-resistant pathogens.An additional issue addressed by the CAP guideline was multidrug-resistant pathogens, specifically Pseudomonas aeruginosa and methicillin-resistant S aureus. In prior CAP guidelines, antibiotic coverage for these pathogens had been recommended in the presence of several risk factors associated with what was termed health care–associated pneumonia. In the current guideline, the focus is on a more limited set of risk factors, especially evidence that the patient was previously infected with either of these pathogens. Moreover, the guideline recommends that in all cases when more expanded antibiotic therapy is initiated, blood and sputum cultures should be obtained to confirm or rule out the presence of these pathogens. If results of cultures are negative and the patient is improving, the expanded therapy for P aeruginosa and methicillin-resistant S aureus should be narrowed within 48 hours of starting therapy.4. Procalcitonin could be helpful in limiting overuse of antibiotics in patients with COVID-19–related pneumonia.Before the COVID-19 pandemic, the inflammatory biomarker procalcitonin was shown to safely reduce antibiotic use in patients with CAP, but much of the effect was related to reducing the duration of therapy as opposed to withholding antibiotics altogether (7). Moreover, no procalcitonin threshold perfectly distinguishes viral from bacterial pneumonia (8). Procalcitonin may also be elevated in patients with COVID-19 because of generalized inflammatory activation rather than bacterial co-infection (9). Still, we endorse the use of a low procalcitonin value early in the course of confirmed COVID-19 illness to guide the withholding or early stopping of antibiotics, especially among patients with less severe disease. Perhaps more important, 5 days of antibiotic therapy is adequate for most patients with CAP.5. Although it is likely that host immunologic processes play a key role in the lung damage that leads to respiratory failure and adverse outcomes in patients with COVID-19, immunomodulating therapy is not currently recommended in patients with pneumonia.Before COVID-19, much attention was given to the potential benefits of adding corticosteroids to the treatment of adults with CAP. However, on the basis of a review of published studies (with an additional study since added [10]), the guideline committee ultimately recommended against using corticosteroids in patients with CAP. We do not currently recommend corticosteroids or other immunomodulating therapies as adjunct treatments for patients with COVID-19–related pneumonia.Looking forward, it is clear there are many unanswered questions in the management of patients with COVID-19–related pneumonia. More detailed epidemiologic studies are needed to help guide the settings in which bacterial co-infection is more common and whether the involved pathogens are the same as those found in prior studies of CAP or if other pathogens, including multidrug-resistant pathogens, are more common. The role of biomarkers, including procalcitonin, should be similarly investigated in this regard. Ongoing trials will help clarify whether immunomodulating therapies are beneficial in patients with COVID-19–related pneumonia.References1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia: an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200:e45-e67. [PMID: 31573350] doi:10.1164/rccm.201908-1581ST CrossrefMedlineGoogle Scholar2. Jain S, Self WH, Wunderink RG, et al; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373:415-27. [PMID: 26172429] doi:10.1056/NEJMoa1500245 CrossrefMedlineGoogle Scholar3. Lidman C, Burman LG, Lagergren A, et al. Limited value of routine microbiological diagnostics in patients hospitalized for community-acquired pneumonia. Scand J Infect Dis. 2002;34:873-9. [PMID: 12587618] CrossrefMedlineGoogle Scholar4. Ye Z, Zhang Y, Wang Y, et al. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review. Eur Radiol. 2020. [PMID: 32193638] doi:10.1007/s00330-020-06801-0 CrossrefMedlineGoogle Scholar5. Guan WJ, Ni ZY, Hu Y, et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-1720. [PMID: 32109013] doi:10.1056/NEJMoa2002032 CrossrefMedlineGoogle Scholar6. Du Y, Tu L, Zhu P, et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan: a retrospective observational study. Am J Respir Crit Care Med. 2020. [PMID: 32242738] doi:10.1164/rccm.202003-0543OC CrossrefMedlineGoogle Scholar7. Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174:84-93. [PMID: 16603606] CrossrefMedlineGoogle Scholar8. Self WH, Balk RA, Grijalva CG, et al. Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis. 2017;65:183-190. [PMID: 28407054] doi:10.1093/cid/cix317 CrossrefMedlineGoogle Scholar9. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-1062. [PMID: 32171076] doi:10.1016/S0140-6736(20)30566-3 CrossrefMedlineGoogle Scholar10. Lloyd M, Karahalios A, Janus E, et al; Improving Evidence-Based Treatment Gaps and Outcomes in Community-Acquired Pneumonia (IMPROVE-GAP) Implementation Team at Western Health. Effectiveness of a bundled intervention including adjunctive corticosteroids on outcomes of hospitalized patients with community-acquired pneumonia: a stepped-wedge randomized clinical trial. JAMA Intern Med. 2019; 179:1052-1060. [PMID: 31282921] doi:10.1001/jamainternmed.2019.1438 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Joshua P. Metlay, MD, PhD; Grant W. Waterer, MB, BS, PhDAffiliations: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (J.P.M.)Royal Perth Hospital and University of Western Australia, Perth, Australia (G.W.W.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-2189.Corresponding Author: Joshua P. Metlay, MD, PhD, Massachusetts General Hospital, 100 Cambridge Street, 16th Floor, Boston, MA 02114; e-mail, jmetlay@mgh.harvard.edu.Current Author Addresses: Dr. Metlay: Massachusetts General Hospital, 100 Cambridge Street, 16th Floor, Boston, MA 02114.Dr. Waterer: Royal Perth Hospital and University of Western Australia, Level 3, Executive Corridor, Royal Perth, Perth, Australia.Author Contributions: Conception and design: J.P. Metlay, G.W. Waterer.Drafting of the article: J.P. Metlay, G.W. Waterer.Critical revision of the article for important intellectual content: J.P. Metlay, G.W. Waterer.Final approval of the article: J.P. Metlay, G.W. Waterer.Collection and assembly of data: J.P. Metlay, G.W. Waterer.This article was published at Annals.org on 7 May 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEarly empiric antibiotic use in COVID-19 patients: results from the international VIRUS registryCommunity-acquired pneumonia: antibiotic therapy approach after the COVID-19 pandemic. A reviewTrends and patterns of antibiotics use in Serbia from 2006 to 2021: Pre-COVID-19 period versus COVID-19 pandemicAntimicrobials in COVID-19: strategies for treating a COVID-19 pandemicSymptoms, Treatment, and Outcomes of COVID-19 Patients Coinfected with Clostridioides difficile: Single-Center Study from NE Romania during the COVID-19 PandemicThe Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and TherapyEvaluation of continuous ampicillin/sulbactam infusion in critically ill patientsNon-Adherence in Adult Male Patients with Community-Acquired Pneumonia: Relative Forgiveness of Amoxicillin versus Respiratory FluoroquinolonesPneumoniaEfficacy of corticosteroids as an adjunctive therapy in the treatment of community-acquired pneumonia: a systematic review and meta-analysisCOVID‐19: Cardiology PerspectiveAetiology of severe community acquired pneumonia in adults identified by combined detection methods: a multi-centre prospective study in ChinaApproaches to Assessing the Safety of Medicines during the COVID-19 Pandemic Using the Example of AzithromycinSHEA statement on antibiotic stewardship in hospitals during public health emergenciesCOVID-19 in spinal cord injury patients at a veterans administration hospital: A case seriesAntimicrobial prescription in severe COVID-19 and CAP: a matched case-control studyImpact of COVID-19 on diagnosis of primary pulmonary coccidioidomycosisCOVID-19-specific transcriptomic signature detectable in blood across multiple cohortsAntimicrobial Resistance Patterns of Bacterial and Fungal Isolates in COVID-19Empiric Antibiotics in COVID 19: A Narrative ReviewBacterial infections and antibiotic utilization varies by coronavirus disease 19 (COVID-19) severity in hospitalized cancer patients: Analysis from the first phase of the pandemicThe feasibility of procalcitonin and CPIS score to reduce inappropriate antibiotics use among severe-critically ill COVID-19 pneumonia patients: A pilot studyMetal(II) Complexes of the Fluoroquinolone Fleroxacin: Synthesis, Characterization and Biological ProfileCommunity-Acquired Pneumonia in Canada During Coronavirus Disease 2019Emergent Virus Reactivation in SARS-CoV-2-Negative Community Acquired Pneumonia Patients During the COVID-19 PandemicEmpirical antibiotic usage and bacterial superinfections in patients with COVID-19 in Japan: A nationwide survey by the Japanese Respiratory Society­­­­­Cefotaxime: A reappraisal for use in lower respiratory tract infectionsAn overview on the current available treatment for COVID-19 and the impact of antibiotic administration during the pandemicUtilization of Antibiotics for Hospitalized Patients with Severe Coronavirus Disease 2019 in Al-Madinah Al-Munawara, Saudi Arabia: A Retrospective StudyCommunity and Hospital Acquired PneumoniaCefotaxime: A Reappraisal in Lower Respiratory Tract InfectionsReducing the use of empiric antibiotic therapy in COVID-19 on hospital admissionThe role of co-infections and secondary infections in patients with COVID-19Repurposing of antibiotics for clinical management of COVID-19: a narrative reviewImpact of COVID-19 on Outpatient Antimicrobial Prescribing Patterns in New York CityCOVID-19 Advanced CareAntibiotic Use and Bacterial Infection among Inpatients in the First Wave of COVID-19: a Retrospective Cohort Study of 64,691 PatientsHybrid Deep Learning Model For Diagnosis Of Covid-19 Using Ct Scans And Clinical/Demographic DataPrevalence of methicillin-resistant Staphylococcus aureus (MRSA) in respiratory cultures and diagnostic performance of the MRSA nasal polymerase chain reaction (PCR) in patients hospitalized with coronavirus disease 2019 (COVID-19) pneumoniaInpatient antibiotic utilization in the Veterans' Health Administration during the coronavirus disease 2019 (COVID-19) pandemicAntimicrobial Stewardship in a Pandemic: Picking Up the PiecesInappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVIDTetracycline antibiotics as precursors of dichloroacetamide and other disinfection byproducts during chlorination and chloraminationAn Approach to Construct and Validate TCM Dataset Effective against Bacterial PneumoniaTopical issues of diagnostics, examination and treatment of patients with COVID-19-associated pneumonia in different countries and continentsBacterial coinfections with coronavirus disease 2019 (COVID-19)Continued use of azithromycin for mild COVID-19 in India: Evidence and implications?ЛІКУВАННЯ ХВОРИХ З COVID-19 НА СУЧАСНОМУ ЕТАПІAntimicrobial Management of Respiratory Infections in Severe Acute Respiratory Syndrome Coronavirus 2 Patients: Clinical and Antimicrobial Stewardship Programs ConundrumsCOVID-19 and kidney transplantation: Results from the TANGO International Transplant ConsortiumCommunity-aquired pneumonia on the background of coronaviral disease (COVID-19): principles of diagnostics and determination of risk factors of pathological process aggravationCOVID-19: An Emerging Threat to Antibiotic Stewardship in the Emergency Department Coinfection of SARS-CoV-2 and Other Respiratory Pathogens 18 August 2020Volume 173, Issue 4 Page: 304-305 Keywords Antibiotics Bacterial pathogens COVID-19 Lungs Pathogens Patients Pneumonia Sputum Treatment guidelines Upper respiratory tract infections ePublished: 7 May 2020 Issue Published: 18 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...