Role of oxygen saturation in early discontinuation of antibiotics for suspected pneumonia
Click Here to Manage Email Alerts
Community-acquired pneumonia (CAP) is associated with an estimated 1 million hospitalizations per year in the United States and is often treated with antibiotics.
Recognized signs and symptoms include fever, chills, myalgias, increased white blood cell count, hypoxia, cough, rales, sputum production, and lung imaging that reveals infiltrates, opacities or densities.
Source: Adobe Stock
However, these findings are nonspecific, with pneumonitis, acute decompensated heart failure, pulmonary emboli and bronchitis potentially presenting similarly. This discrepancy begs the question of how many of those 1 million hospitalizations are truly due to pneumonia.
There is evidence suggesting that CAP may be overdiagnosed in practice. One prospective cohort study found that only 37% of 1,464 patients in the ICU treated with antibiotics for pneumonia met full diagnostic criteria. It can be extrapolated that some of these patients received antibiotics superfluously.
Much has been made of the negative impact of unnecessary antibiotic exposure on hospital stay, health care costs, growth of antimicrobial resistance and Clostridioides difficile infection. Although guidelines recommend an adequate treatment duration of 5 and 7 days for CAP and hospital-acquired pneumonia, respectively, patients commonly receive extended courses of therapy. One study found that nearly 70% of patients received antibiotics beyond the guideline-recommended duration. Patients who received extended courses did not demonstrate significant benefit in 30-day mortality, readmission or ED visit but did show a 5% increased risk for antibiotic-related adverse events with each extra day of therapy received.
To combat this, researchers have been investigating the merit of 3-day courses of treatment for those who are clinically stable, with one randomized control trial finding that the shorter regimen was noninferior to a standard treatment duration. Given that pneumonia may be overdiagnosed, and that those diagnosed often receive excessive amounts of antibiotic treatment, there has been a growing interest in researching potential indicators to identify patients with CAP who may be good candidates for early discontinuation of antibiotics.
Potential role for oxygen saturation
One such indicator could be oxygen saturations. Hypoxia (oxygen saturations less than 95%) occurs in pneumonia as a result of pathogens invading the lung alveoli, with the resulting inflammatory response causing an alveolar-capillary leak and filling the space. Hypoxia has been noted to be an independent predictor of radiograph-confirmed pneumonia, along with fever, rales and tachycardia. Conversely, in practice, hospitalized patients may be treated for CAP even if their oxygen saturations are normal (95% or above).
One retrospective cohort study of CAP outpatients challenges this practice, finding that oxygen saturations greater than 92% were not significantly associated with either mortality or hospitalization after 30 days. Besides suggesting the possibility of an alternative diagnosis, preserved oxygen saturations in true pneumonia could indicate mild cases with minimal bacterial invasion of alveolar spaces. These data beg the question of whether oxygen saturations of 95% or greater could be a viable marker for early discontinuation of therapy.
New research
Klompas and colleagues recently attempted to address this hypothesis in a retrospective analysis published in Clinical Infectious Diseases in June 2022. They examined adult patients treated with antibiotics for pneumonia at four Massachusetts hospitals between May 2017 and February 2021. To be included, median oxygen saturations had to be 95% or greater on room air during the first 2 days of treatment. Patients were excluded if they had positive blood cultures, were missing vital signs on first days of antibiotics or had discharge diagnoses of potentially confounding conditions like empyema, cystic fibrosis or bronchiectasis. Outcomes of those who received 1 to 2 days of antibiotics were compared with those who received standard 5 to 8 days of treatment, including post-discharge antibiotics.
Patients were propensity matched with variables like patient demographics, comorbidities, vital signs, laboratory values, baseline medications, culture data and more. This matching system was used to curtail the notion that physicians may be prescribing shorter courses of treatment to those who appeared “more stable” or had data that suggested a nonbacterial cause of symptoms.
Of the 4,478 propensity-matched patients who met study criteria, 2,239 (50%) received 1 to 2 days of therapy and 2,239 (50%) received 5 to 8 days of treatment, with 77% receiving antibiotics for pneumonia within the first 2 days of hospitalization. Results of the study are listed below and were consistent in follow-up sensitivity analysis. The study found no significant differences in:
- hospital mortality (2.1% vs. 2.8%; HR = 1.13 [95% CI, 0.51-1.09]);
- 30-day readmissions (16% vs. 15.8%; OR = 1.01 [95% CI, 0.86-1.19]);
- 30-day mortality (4.6% vs. 5.1%; OR = 0.91 [95% CI, 0.69-1.19]); or
- 90-day C. difficile infection (1.3% vs. 0.8%; OR =1.67 [95% CI, 0.94-2.99]).
However, the study did show significant differences in the following outcomes favoring the group that received 1 to 2 days of therapy:
- mean days to discharge (6.1 vs. 6.6; HR = 1.13 [95% CI, 1.07-1.19]);
- 30-day hospital-free days (23.1 vs. 22.7; mean difference = 0.44 [95% CI, 0.09-0.78]); and
- antibiotic-free days alive (25.9 vs. 21.5; mean difference = 4.4 [95% CI, 4.08-4.69]).
The authors concluded that there was no evidence of harm with 1 to 2 vs. 5 to 8 days of antibiotics to treat possible pneumonia in patients who had oxygen saturations of 95% or greater on room air. Strengths of the study include the variety of outcomes studied and the propensity-matching system, which adds confidence regarding potential prescriber bias in choosing a treatment duration. They self-identified several limitations in their study, particularly relating to it being an observational study and conducted in a small number of centers in a specific region of the U.S., limiting generalizability.
However, another limitation is also present. The authors specify that these data are applicable to the treatment of “possible pneumonia,” indirectly acknowledging that they did not investigate whether the patients truly met diagnostic criteria, as determined by imaging. Although (as previously discussed in this article) it is true that many patients ultimately treated for pneumonia do not meet diagnostic criteria, not differentiating true pneumonia cases from others introduces confounders to the results. How many of these patients had true pneumonia vs. another cause like bronchitis or pneumonitis? It is possible that any false cases of pneumonia could skew the data. Also, how many of these cases were bacterial or had viral causes identified, and did that impact the success of one treatment duration or the other? These questions are unfortunately left unanswered.
Conclusion
Ultimately, the study by Klompas and colleagues introduces an intriguing if incomplete concept to the growing research for early discontinuation of antibiotics for pneumonia. Ideally these findings will provide a platform for future researchers to conduct further investigations into the role of oxygen saturations in pneumonia treatment. In applying their findings to practice, clinicians can consider oxygen saturations as one part of the many signs and symptoms that contribute to clinical stability to guide their antibiotic duration decision.
- References:
- Bergin SP, et al. Chest. 2020;doi:10.1016/j.chest.2020.06.034.
- Dinh A, et al. Lancet. 2021;doi:10.1016/S0140-6736(21)00313-5.
- File TM Jr, Marrie TJ. Postgrad Med. 2010;doi:10.3810/pgm.2010.03.2130.
- Klompas M, et al. Clin Infect Dis. 2022;doi:10.1093/cid/ciac616.
- Majumdar SR, et al. Clin Infect Dis. 2011;doi:10.1093/cid/ciq076.
- Mandell LA. Postgrad Med. 2015;doi:10.1080/00325481.2015.1074030.
- Moore M, et al. Eur Respir J. 2017;doi:10.1183/13993003.00434-2017.
- Vaughn VM, et al. Ann Intern Med. 2019;doi:10.7326/M18-3640.
- For more information:
- Michael Deaney, PharmD, is a PGY1 pharmacy practice resident at Denver Health Medical Center.
- Kati Shihadeh, PharmD, BCIDP, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at katherine.shihadeh@dhha.org.
Collapse
Read more about
Click Here to Manage Email Alerts