Mitigating Antibiotic Resistance in Respiratory Infections: An Expert Roundtable

Welcome to Lungs & Bugs, a collaboration between Pulmonology Advisor and Infectious Disease Advisor. Each month, we will feature content on disease states related to both specialties, including pneumonia, influenza, and tuberculosis. We hope this endeavor will encourage more open dialogue between pulmonologists and infectious disease clinicians.

This month, in light of the continued battle against antibiotic resistance, we present a roundtable interview on the pros and cons of antibiotic therapy in patients admitted to intensive care units with severe respiratory disease.

As a result of increasing antibiotic resistance, clinicians are often in the challenging position of acting in the best interest of each patient while trying to avoid contributing to the problem with the unnecessary or inappropriate use of antibiotics. However, many studies have shown that delaying antibiotic administration for serious infection in the emergency department (ED) can have devastating consequences.

In a 2018 observational cohort study of 117 patients admitted to the intensive care unit (ICU) with sepsis or septic shock, there was an increase in mortality risk for each hour of delay in ordering (22%) or administering (15%) antibiotics after triage.¹ These delays were also associated with a greater number of days spent in the hospital and the ICU. In line with these findings, the authors of a 2017 systematic review examined 14 studies regarding antibiotic administration in patients with sepsis in the ED, and found the greatest mortality benefit in those individuals who received appropriate antibiotic treatment within 1 hour of recognition.²

Pulmonology Advisor interviewed the following experts to discuss considerations pertaining to antibiotic therapy when treating patients in the ICU for pneumonia or tuberculosis: Keira A. Cohen, MD, assistant professor of medicine in the Division of Pulmonary and Critical Care Medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland; Stanley Deresinski Deresinski, MD, clinical professor of medicine in the Division of Infectious Diseases and Geographic Medicine at Stanford University Medical Center in California and medical director of the Stanford Antimicrobial Stewardship Program; and Angela Rogers, MD, assistant professor of medicine in the Division of Pulmonary and Critical Care at Stanford.

Pulmonology Advisor: What are the risks of delaying antibiotics for pneumonia? For tuberculosis (TB)? How are these situations typically approached in the ICU?

Dr Cohen: For pneumonia with septic shock, time to initiation of appropriate antibiotic treatment is of critical importance to optimize treatment outcomes. If someone requires ICU-level care for septic shock from pneumonia or another severe infection, mortality increases with each hour that antibiotic treatment is delayed. 

Administering early, appropriate antibiotic treatment is important, but when a patient initially presents to an ICU with sepsis or septic shock, we often do not know the identity of the precise organism responsible for the clinical presentation. So, without knowing the exact identity of the infecting organism, we choose empiric broad-spectrum antibiotic therapies based on guidelines from professional societies and each hospital’s local bacterial resistance patterns. When the patient stabilizes and the infectious agent can be identified, then we are able to change to narrow-spectrum antibiotics directed at the particular pathogen.

With respect to delaying antibiotics for TB, in the United States, we are fortunate that TB numbers have declined significantly. Currently, there are only approximately 10,000 individuals who are diagnosed with TB in the United States every year, which makes TB a rare disease. Thus, the issue of encountering TB in the ICU is quite uncommon, as the overwhelming majority of patients with active TB do not require ICU-level care. 

That being said, there are a few cases every year in which an individual suspected to have a routine bacterial pneumonia is later found to have active TB as the cause. Individuals with active TB also need timely appropriate antibiotic treatment. Delaying antibiotic treatment in TB can lead to a longer window of time in which that person is able to spread this infection to others. For routine bacterial pneumonias, treatment delays do not represent a similar infection control issue. 

Dr Deresinski: Most cases of pneumonia acquired by individuals living in the community are caused by viruses or bacteria. For treatable causes, early initiation of antibiotic therapy is preferred in order to avoid progression of the infection. The only viral cause that is currently treatable is that due to influenza, for which oseltamivir is indicated. A second drug effective against influenza virus infection, baloxavir, has recently also become available. The problem for the clinician is that, with some exceptions, it may not be possible to distinguish between viral and bacterial pneumonia without the use of rapid diagnostic tests – which, however, may not be readily available in all clinical settings.  

Dr Rogers: In both bacterial pneumonia and TB, you are balancing the benefits of treatment right away and avoiding the disease getting worse vs exposing patients to unnecessary or potentially harmful drugs. With bacterial pneumonia, the risk is mostly for the patient who is being treated: their condition could get worse. I work mainly in the ICU, and with patients who are already sick where there is no room for error or waiting if they get worse, so we have a very low threshold for starting empiric antibiotic treatment.

With TB treatment, certainly there is the risk to the patient for delaying, but there is also a big societal risk: TB is often infectious, and while you are waiting for results to come back, there is the potential that individuals with TB may be out in society exposing others.