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Abstract

Background

Suspected pneumonia is the most common indication for antibiotics in hospitalized patients but is frequently overdiagnosed. We explored whether normal oxygenation could be used as an indicator to support early discontinuation of antibiotics.

Methods

We retrospectively identified all patients started on antibiotics for pneumonia in 4 hospitals with oxygen saturations ≥95% on ambient air, May 2017–February 2021. We propensity-matched patients treated 1–2 days vs 5–8 days and compared hospital mortality and time to discharge using subdistribution hazard ratios (SHRs). Secondary outcomes included readmissions, 30-day mortality, Clostridioides difficile infections, hospital-free days, and antibiotic-free days.

Results

Among 39 752 patients treated for possible pneumonia, 10 012 had median oxygen saturations ≥95% without supplemental oxygen. Of these, 2871 were treated 1–2 days and 2891 for 5–8 days; 4478 patients were propensity-matched. Patients treated 1–2 vs 5–8 days had similar hospital mortality (2.1% vs 2.8%; SHR, 0.75 [95% confidence interval {CI}, .51–1.09]) but less time to discharge (6.1 vs 6.6 days; SHR, 1.13 [95% CI, 1.07–1.19]) and more 30-day hospital-free days (23.1 vs 22.7; mean difference, 0.44 [95% CI, .09–.78]). There were no significant differences in 30-day readmissions (16.0% vs 15.8%; odds ratio [OR], 1.01 [95% CI, .86–1.19]), 30-day mortality (4.6% vs 5.1%; OR, 0.91 [95% CI, .69–1.19]), or 90-day C. difficile infections (1.3% vs 0.8%; OR, 1.67 [95% CI, .94–2.99]).

Conclusions

One-quarter of hospitalized patients treated for pneumonia had oxygenation saturations ≥95% on ambient air. Outcomes were similar with 1–2 vs 5–8 days of antibiotics. Normal oxygenation levels may help identify candidates for early antibiotic discontinuation. Prospective trials are warranted.

pneumonia, antibiotic stewardship, oxygenation, quality improvement

Suspected respiratory tract infection is the most common indication for antibiotics in hospitalized patients [1–4]. A substantial fraction of antibiotics prescribed for possible pneumonia, however, may be unnecessary [5]. Expert reviews, computed tomography audits, and autopsy series suggest that 30%–50% of hospitalized patients diagnosed with pneumonia do not, in fact, have pneumonia [6–12]. One of the main drivers of antibiotic overprescribing is the subjectivity and lack of specificity of the core clinical signs and symptoms used to diagnose pneumonia. Shortness of breath, changes in sputum production, and radiographic opacities are all common but nonspecific findings in hospitalized patients [13, 14]. Clinicians are wary of missing the diagnosis of pneumonia, however, and therefore tend to err on the side of prescribing even if the diagnosis is uncertain. Better strategies are needed to help clinicians at the bedside determine if antibiotics are warranted or not, and if started, whether to continue them or stop.

One very simple and sensitive (albeit nonspecific) sign that may differentiate between true and serious respiratory infections vs noninfectious mimicking conditions or very mild pneumonias is oxygen saturation. Pneumonia, by definition, involves invasion of the lung parenchyma. The absence of impaired gas exchange therefore makes severe pneumonia unlikely. Indeed, there is a strong and consistent association between the magnitude of impaired oxygenation in patients with possible pneumonia and their risk for death and other poor outcomes [15–18]. Conversely, oxygen saturations ≥95% are associated with a lower probability of true infection [18], and oxygen saturations >92% have been associated with minimal marginal risk for death or hospitalization among outpatients treated for pneumonia [19].

Focusing on oxygenation levels to inform the decision to start or continue antibiotics could have a large potential effect on antibiotic utilization. Up to one-third of hospitalized patients treated for pneumonia have oxygen saturations ≥95% without supplemental oxygen [10, 20, 21]. There are very few studies, however, on the safety of stopping antibiotics in this population [22]. We therefore undertook a retrospective analysis of outcomes among hospitalized patients with oxygen saturations ≥95% without supplemental oxygen who were treated for possible pneumonia with very short courses of antibiotics (1–2 days) vs propensity-matched patients treated with more conventional courses (5–8 days).

METHODS

We identified all patients aged ≥18 years admitted to 4 hospitals in eastern Massachusetts between May 2017 and February 2021 who were treated with antibiotics with a stated indication of pneumonia. Study hospitals included 2 large tertiary referral hospitals (Brigham and Women’s Hospital and Massachusetts General Hospital) and 2 community hospitals (Faulkner Hospital and Newton Wellesley Hospital). Granular clinical data were extracted from an Enterprise Data Warehouse populated by the electronic health record system shared by all study hospitals (Epic Systems, Verona, Wisconsin) including demographics, diagnosis codes, locations, services, vital signs, laboratory values, medications, and antibiotic indications. Providers are required to specify an indication whenever new antibiotics are ordered for inpatients. This is done within the antibiotic order screen in the electronic health record by selecting from a structured list of options that includes pneumonia. Providers can also enter a free text indication. Validation studies suggest that the indications specified by clinicians accurately reflect their working diagnoses at the time of prescription as specified in their concurrent clinical notes [10, 23].

We limited the population to patients with median daily oxygen saturation levels of ≥95% without supplemental oxygen on both the first and second calendar days of antibiotics. Median oxygen saturation levels were calculated using all recorded values on a calendar day. We excluded patients with positive blood cultures (other than common skin contaminants), missing vital signs on the first day of antibiotics, or discharge diagnosis codes for empyema, cystic fibrosis, or bronchiectasis (E84, J85, J86) since standard of care for these conditions includes longer antibiotic courses. If a patient was admitted more than once during the study period, then a single admission was selected at random. Missing laboratory values were imputed from the closest measured value within 2 days before or after the first day of antibiotics, but if no measurements were available, then missing values were imputed as normal.

We compared outcomes for patients treated with 1–2 days of antibiotics vs those treated with 5–8 days of antibiotics by propensity-matching those treated for 1–2 days to those treated 5–8 days using a caliper of 0.1 times the standard deviation of the estimated logit propensity score [24]. Postdischarge antibiotics were included when calculating duration of antibiotics. We chose these 2 intervals (1–2 days and 5–8 days) to provide clear separation in treatment durations between groups and because we hypothesized clinical equipoise among clinicians on whether patients with normal oxygenation levels have pneumonia or not: we reasoned that clinicians who stopped antibiotics within 1–2 days likely decided against pneumonia whereas those who treated for 5–8 days opted in favor of pneumonia. We recognize, however, that clinicians may be more likely to stop antibiotics if evidence for pneumonia is more equivocal. We therefore propensity-matched patients treated 1–2 days to patients treated 5–8 days using an extensive array of granular clinical parameters including patients’ demographics, comorbidities, vital signs, laboratory values, culture orders, respiratory viral studies, and baseline medications. We also limited the analysis to patients who survived at least 5 days counting from the first day of antibiotics in order to assure that antibiotic courses of <5 days were due to clinical choice, not early death, and thus mitigate survivor bias in favor of those treated with longer courses.

Propensity scores for treatment interval were calculated by stratifying patients by hospital and then within each hospital using patients’ demographics (age, race, sex), clinical service on the first day of antibiotics (medicine, neurology, obstetrics, oncology, surgery, cardiology, cardiac surgery), presence in an intensive care unit on the first day of antibiotics, comorbidities (congestive heart failure, renal failure, liver disease, metastatic cancer, solid tumor, diabetes, cerebrovascular disease, pulmonary circulation disorder), vital signs on the first day of antibiotics (maximum temperature, median respiratory rate, maximum heart rate, minimum systolic blood pressure), laboratory values on the first day of antibiotics (maximum white blood cell count, minimum hematocrit, minimum platelets, maximum creatinine, minimum sodium, maximum glucose, maximum alanine aminotransferase, maximum bilirubin, maximum albumin, maximum international normalized ratio), vasopressor use on the first day of antibiotics, antibiotic exposure for other indications between admission and the first day of antibiotics for pneumonia, number of days from admission until first day of antibiotics, whether blood cultures were obtained, whether a sputum culture was obtained, whether sputum cultures were positive for potentially pathogenic organisms (ie, organisms other than coagulase-negative staphylococci, Enterococcus, and Candida), and whether any assays for respiratory viruses were positive (including severe acute respiratory syndrome coronavirus 2, influenza, respiratory syncytial virus, parainfluenza, rhinovirus, human metapneumovirus, and adenovirus). Patients’ comorbidities were derived using the methods of Charlson and Elixhauser [25, 26]. We used the median respiratory rate rather than the minimum or maximum given that this parameter is prone to wide fluctuation over the course of a day depending on patients’ activities and clinical interventions.

We compared hospital death, hospital discharge, 30-day mortality, 30-day readmissions, and 90-day positive Clostridioides difficile toxin assays counting from the first day of antibiotics using sample proportions, and total antibiotic days, total antibiotic-free days alive, and total hospital-free days alive within 30 days of the first day of antibiotics using sample means. We calculated P values for comparisons in the total and matched cohorts using 2-sample t tests.

We further estimated measures of association for short vs conventional treatment groups among propensity-matched patients using Fine and Gray regression for propensity score–matched data [27] to estimate subdistribution hazard ratios (SHRs) for hospital death and discharge and logistic regression to estimate odds ratios (ORs) for 30-day mortality, 30-day readmission, and 90-day positive C. difficile toxin assays. We used linear regression to estimate mean differences for total antibiotic days, total antibiotic-free days alive, and total hospital-free days alive within 30 days of the first day of antibiotics. We generated 95% confidence intervals (CIs) for odds ratios (ORs) and mean differences using cluster-robust standard errors to account for the paired nature of the data.

We performed sensitivity analyses limited to patients with community-acquired pneumonia (first day of antibiotics on hospital day 1–2), hospital-acquired pneumonia (first day of antibiotics on hospital day ≥3), patients in whom sputum cultures were obtained, patients with positive sputum cultures, and patients with discharge diagnosis codes for pneumonia (J13–J18). We also did a sensitivity analysis in which we matched patients using their clinical parameters from the second day of antibiotics since decision making regarding duration of antibiotics may have been made on the basis of patients’ clinical parameters on the second day of treatment. All calculations were performed using R version 4.03 software. The study was approved by the Mass General Brigham Institutional Review Board.

RESULTS

There were 39 752 patients started on antibiotics with a stated indication of pneumonia during the study period. Of these, 10 012 had a median oxygen saturation of ≥95% without supplemental oxygen on the first and second days of antibiotics. After applying the study exclusion criteria and limiting to patients treated for 1–2 or 5–8 days, there were 5762 patients remaining (2871 treated for 1–2 days and 2891 treated for 5–8 days). After propensity matching, 4478 patients were included in the primary analysis (2239 in each group). Characteristics of patients before and after propensity matching are shown in Table 1. Within the propensity-matched set, average age was 66 years, 55% were male, 68% were white, 73% were on an internal medicine service, 23% had cancer, 28% had diabetes, 26% had renal failure, and 26% had congestive heart failure. Antibiotics for pneumonia were started within the first 2 days of hospitalization in 3466 of 4478 (77%) and on hospital day 3 or later in in the remainder. Standardized differences between patients treated for 1–2 days vs those treated for 5–8 days were <0.1 on all patient characteristics after propensity matching [28].

Table 1.
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Characteristics of Hospitalized Patients Treated With 1–2 Days Versus 5–8 Days of Antibiotics for Possible Pneumonia Who Had Oxygen Saturations ≥95% on Ambient Air

Total CohortPropensity-Matched Cohort
Characteristic1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)Std Diff1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)Std Diff
Demographics
ȃAge, y, mean (SD)66.1 (18.2)64.9 (18.5)0.0765.4 (18.3)65.5 (18.5)0.01
ȃMale sex1543 (53.7%)1584 (54.8%)0.021220 (54.5%)1202 (53.7%)0.02
ȃRace/ethnicity
ȃȃWhite1925 (67.0%)2008 (69.5%)0.051511 (67.5%)1514 (67.6%)0.01
ȃȃBlack400 (13.9%)386 (13.4%)0.02312 (13.9%)312 (13.9%)0.01
ȃȃHispanic60 (2.1%)48 (1.7%)0.0342 (1.9%)39 (1.7%)0.01
ȃȃAsian134 (4.7%)131 (4.5%)0.0199 (4.4%)113 (5.0%)0.01
ȃȃOther/missing352 (12.3%)318 (11.0%)0.04275 (12.3%)261 (11.7%)0.01
Hospital
ȃTertiary hospital 1822 (29%)796 (28%)0.02633 (28.3%)633 (28.3%)0.00
ȃTertiary hospital 21301 (45%)1411 (49%)0.081084 (48.4%)1084 (48.4%)0.00
ȃCommunity hospital 1384 (13%)295 (10%)0.09244 (10.9%)244 (10.9%)0.00
ȃCommunity hospital 2364 (13%)389 (14%)0.03278 (12.4%)278 (12.4%)0.00
Clinical servicea
ȃCardiac surgery8 (0.3%)11 (0.4%)0.027 (0.3%)6 (0.3%)0.02
ȃCardiology92 (3.2%)61 (2.1%)0.0753 (2.4%)58 (2.6%)0.01
ȃEmergency51 (1.8%)57 (2.0%)0.0247 (2.1%)48 (2.1%)0.02
ȃGynecology3 (0.1%)5 (0.2%)0.033 (0.1%)2 (0.1%)0.00
ȃMedicine2165 (75.8%)2029 (70.3%)0.121662 (74.2%)1626 (72.6%)0.04
ȃNeurology86 (3.0%)94 (3.3%)0.0267 (3.0%)72 (3.2%)0.00
ȃObstetrics9 (0.3%)8 (0.3%)0.005 (0.2%)7 (0.3%)0.01
ȃOncology274 (9.6%)398 (13.8%)0.13253 (11.3%)268 (12.0%)0.04
ȃSurgery127 (4.4%)182 (6.3%)0.09109 (4.9%)124 (5.6%)0.02
Comorbidities
ȃCongestive heart failure807 (28.1%)666 (23.0%)0.02582 (26.0%)569 (25.4%)0.03
ȃRenal failure759 (26.4%)734 (25.4%)0.03589 (26.3%)590 (26.4%)0.04
ȃLiver disease228 (7.9%)285 (9.9%)0.12196 (8.8%)199 (8.9%)0.01
ȃCancer577 (20.1%)713 (24.6%)0.03501 (22.4%)525 (23.4%)0.03
ȃDiabetes854 (29.7%)791 (27.4%)0.12640 (28.6%)629 (28.1%)0.02
ȃNeurological disease425 (14.8%)439 (15.2%)0.02325 (14.5%)318 (14.2%)0.01
ȃElixhauser score, mean (SD)10.8 (11.7)11.9 (12.2)0.0911.0 (12.0)11.4 (12.1)0.03
Clinical characteristics
ȃAntibiotic exposure before pneumoniab297 (10.3%)460 (15.9%)0.17272 (12.1%)296 (13.2%)0.02
ȃIntensive care exposure before pneumoniab134 (4.7%)251 (8.7%)0.16119 (5.3%)135 (6.0%)0.03
ȃHospital days before pneumoniab, mean (SD)1.3 (4.4)2.2 (6.0)0.061.5 (4.1)1.7 (4.4)0.05
ȃBlood cultures drawn1370 (47.7%)1718 (59.4%)0.241166 (52.1%)1187 (53.0%)0.01
ȃSputum cultures obtained397 (13.8%)681 (23.6%)0.25380 (17.0%)380 (17.0%)0.02
ȃSputum cultures positive92 (3.2%)176 (6.1%)0.1488 (3.9%)97 (4.3%)0.02
ȃGram positives40 (1.4%)88 (3.0%)0.1140 (1.8%)42 (1.9%)0.03
ȃEnteric gram negatives35 (1.2%)73 (2.5%)0.1034 (1.5%)41 (1.8%)0.00
ȃNonfermenters23 (0.8%)28 (1.0%)0.0219 (0.8%)22 (1.0%)0.01
ȃPositive respiratory viral assay262 (9.1)199 (6.9)0.08183 (8.2)165 (7.4)0.03
ȃVital signs
ȃȃMaximum temperature, °C, mean (SD)37.3 (0.8)37.6 (0.8)0.2937.4 (0.8)37.4 (0.8)0.00
ȃȃMedian daily respiratory rate, breaths/min, mean (SD)19.3 (2.7)19.5 (2.8)0.0719.4 (2.7)19.3 (2.6)0.04
ȃȃMaximum heart rate, beats/min, mean (SD)98.4 (20.9)101.6 (20.8)0.1599.7 (21.3)99.6 (20.5)0.01
ȃȃMedian systolic blood pressure, mm Hg, mean (SD)130.3 (21.6)127.5 (21.1)0.13128.8 (20.7)128.8 (21.5)0.00
ȃȃVasopressors first day of pneumonia29 (1.0%)50 (1.7%)0.1626 (1.2%)28 (1.3%)0.02
ȃLaboratory values, mean (SD)
ȃȃWBC count, 109 cells/L9.7 (6.8)10.8 (6.8)0.1610.0 (5.8)10.3 (5.7)0.05
ȃȃHemoglobin, g/dL11.5 (2.3)11.1 (2.3)0.0411.3 (2.4)11.3 (2.2)0.00
ȃȃHematocrit, %34.9 (6.7)33.8 (6.4)0.1734.4 (6.7)34.3 (6.3)0.02
ȃȃPlatelets, 109 cells/L233.1 (111.2)231.4 (130.4)0.01233.6 (115.9)232.9 (114.2)0.01
ȃȃCreatinine, mg/dL1.4 (1.7)1.3 (1.3)0.071.4 (1.6)1.3 (1.4)0.07
ȃȃSodium, mmol/L137.3 (4.7)137.0 (4.9)0.06137.2 (4.9)137.1 (4.8)0.02
ȃȃALT, U/L32.5 (61.3)33.7 (81.8)0.0233.3 (65.1)31.8 (47.2)0.03
ȃȃBilirubin, mg/dL0.7 (1.2)0.8 (2.2)0.060.7 (1.3)0.7 (1.3)0.00
ȃȃAlbumin, g/dL3.7 (0.6)3.6 (0.6)0.173.7 (0.6)3.7 (0.6)0.00
ȃȃINR1.2 (0.7)1.3 (0.8)0.131.2 (0.7)1.2 (0.7)0.00
ȃȃGlucose, mg/dL148.7 (83.6)153.8 (89.9)0.06150.9 (87.8)149.9 (81.4)0.01
Total CohortPropensity-Matched Cohort
Characteristic1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)Std Diff1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)Std Diff
Demographics
ȃAge, y, mean (SD)66.1 (18.2)64.9 (18.5)0.0765.4 (18.3)65.5 (18.5)0.01
ȃMale sex1543 (53.7%)1584 (54.8%)0.021220 (54.5%)1202 (53.7%)0.02
ȃRace/ethnicity
ȃȃWhite1925 (67.0%)2008 (69.5%)0.051511 (67.5%)1514 (67.6%)0.01
ȃȃBlack400 (13.9%)386 (13.4%)0.02312 (13.9%)312 (13.9%)0.01
ȃȃHispanic60 (2.1%)48 (1.7%)0.0342 (1.9%)39 (1.7%)0.01
ȃȃAsian134 (4.7%)131 (4.5%)0.0199 (4.4%)113 (5.0%)0.01
ȃȃOther/missing352 (12.3%)318 (11.0%)0.04275 (12.3%)261 (11.7%)0.01
Hospital
ȃTertiary hospital 1822 (29%)796 (28%)0.02633 (28.3%)633 (28.3%)0.00
ȃTertiary hospital 21301 (45%)1411 (49%)0.081084 (48.4%)1084 (48.4%)0.00
ȃCommunity hospital 1384 (13%)295 (10%)0.09244 (10.9%)244 (10.9%)0.00
ȃCommunity hospital 2364 (13%)389 (14%)0.03278 (12.4%)278 (12.4%)0.00
Clinical servicea
ȃCardiac surgery8 (0.3%)11 (0.4%)0.027 (0.3%)6 (0.3%)0.02
ȃCardiology92 (3.2%)61 (2.1%)0.0753 (2.4%)58 (2.6%)0.01
ȃEmergency51 (1.8%)57 (2.0%)0.0247 (2.1%)48 (2.1%)0.02
ȃGynecology3 (0.1%)5 (0.2%)0.033 (0.1%)2 (0.1%)0.00
ȃMedicine2165 (75.8%)2029 (70.3%)0.121662 (74.2%)1626 (72.6%)0.04
ȃNeurology86 (3.0%)94 (3.3%)0.0267 (3.0%)72 (3.2%)0.00
ȃObstetrics9 (0.3%)8 (0.3%)0.005 (0.2%)7 (0.3%)0.01
ȃOncology274 (9.6%)398 (13.8%)0.13253 (11.3%)268 (12.0%)0.04
ȃSurgery127 (4.4%)182 (6.3%)0.09109 (4.9%)124 (5.6%)0.02
Comorbidities
ȃCongestive heart failure807 (28.1%)666 (23.0%)0.02582 (26.0%)569 (25.4%)0.03
ȃRenal failure759 (26.4%)734 (25.4%)0.03589 (26.3%)590 (26.4%)0.04
ȃLiver disease228 (7.9%)285 (9.9%)0.12196 (8.8%)199 (8.9%)0.01
ȃCancer577 (20.1%)713 (24.6%)0.03501 (22.4%)525 (23.4%)0.03
ȃDiabetes854 (29.7%)791 (27.4%)0.12640 (28.6%)629 (28.1%)0.02
ȃNeurological disease425 (14.8%)439 (15.2%)0.02325 (14.5%)318 (14.2%)0.01
ȃElixhauser score, mean (SD)10.8 (11.7)11.9 (12.2)0.0911.0 (12.0)11.4 (12.1)0.03
Clinical characteristics
ȃAntibiotic exposure before pneumoniab297 (10.3%)460 (15.9%)0.17272 (12.1%)296 (13.2%)0.02
ȃIntensive care exposure before pneumoniab134 (4.7%)251 (8.7%)0.16119 (5.3%)135 (6.0%)0.03
ȃHospital days before pneumoniab, mean (SD)1.3 (4.4)2.2 (6.0)0.061.5 (4.1)1.7 (4.4)0.05
ȃBlood cultures drawn1370 (47.7%)1718 (59.4%)0.241166 (52.1%)1187 (53.0%)0.01
ȃSputum cultures obtained397 (13.8%)681 (23.6%)0.25380 (17.0%)380 (17.0%)0.02
ȃSputum cultures positive92 (3.2%)176 (6.1%)0.1488 (3.9%)97 (4.3%)0.02
ȃGram positives40 (1.4%)88 (3.0%)0.1140 (1.8%)42 (1.9%)0.03
ȃEnteric gram negatives35 (1.2%)73 (2.5%)0.1034 (1.5%)41 (1.8%)0.00
ȃNonfermenters23 (0.8%)28 (1.0%)0.0219 (0.8%)22 (1.0%)0.01
ȃPositive respiratory viral assay262 (9.1)199 (6.9)0.08183 (8.2)165 (7.4)0.03
ȃVital signs
ȃȃMaximum temperature, °C, mean (SD)37.3 (0.8)37.6 (0.8)0.2937.4 (0.8)37.4 (0.8)0.00
ȃȃMedian daily respiratory rate, breaths/min, mean (SD)19.3 (2.7)19.5 (2.8)0.0719.4 (2.7)19.3 (2.6)0.04
ȃȃMaximum heart rate, beats/min, mean (SD)98.4 (20.9)101.6 (20.8)0.1599.7 (21.3)99.6 (20.5)0.01
ȃȃMedian systolic blood pressure, mm Hg, mean (SD)130.3 (21.6)127.5 (21.1)0.13128.8 (20.7)128.8 (21.5)0.00
ȃȃVasopressors first day of pneumonia29 (1.0%)50 (1.7%)0.1626 (1.2%)28 (1.3%)0.02
ȃLaboratory values, mean (SD)
ȃȃWBC count, 109 cells/L9.7 (6.8)10.8 (6.8)0.1610.0 (5.8)10.3 (5.7)0.05
ȃȃHemoglobin, g/dL11.5 (2.3)11.1 (2.3)0.0411.3 (2.4)11.3 (2.2)0.00
ȃȃHematocrit, %34.9 (6.7)33.8 (6.4)0.1734.4 (6.7)34.3 (6.3)0.02
ȃȃPlatelets, 109 cells/L233.1 (111.2)231.4 (130.4)0.01233.6 (115.9)232.9 (114.2)0.01
ȃȃCreatinine, mg/dL1.4 (1.7)1.3 (1.3)0.071.4 (1.6)1.3 (1.4)0.07
ȃȃSodium, mmol/L137.3 (4.7)137.0 (4.9)0.06137.2 (4.9)137.1 (4.8)0.02
ȃȃALT, U/L32.5 (61.3)33.7 (81.8)0.0233.3 (65.1)31.8 (47.2)0.03
ȃȃBilirubin, mg/dL0.7 (1.2)0.8 (2.2)0.060.7 (1.3)0.7 (1.3)0.00
ȃȃAlbumin, g/dL3.7 (0.6)3.6 (0.6)0.173.7 (0.6)3.7 (0.6)0.00
ȃȃINR1.2 (0.7)1.3 (0.8)0.131.2 (0.7)1.2 (0.7)0.00
ȃȃGlucose, mg/dL148.7 (83.6)153.8 (89.9)0.06150.9 (87.8)149.9 (81.4)0.01

Data are presented as No. (%) unless otherwise indicated.

Abbreviations: ALT, alanine aminotransferase; INR, international normalized ratio; SD, standard deviation; Std Diff, standardized difference; WBC, white blood cell.

Clinical service on hospital day 2.

Exposures measured prior to the first day of antibiotics with a stated indication of pneumonia.

Table 1.
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Characteristics of Hospitalized Patients Treated With 1–2 Days Versus 5–8 Days of Antibiotics for Possible Pneumonia Who Had Oxygen Saturations ≥95% on Ambient Air

Total CohortPropensity-Matched Cohort
Characteristic1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)Std Diff1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)Std Diff
Demographics
ȃAge, y, mean (SD)66.1 (18.2)64.9 (18.5)0.0765.4 (18.3)65.5 (18.5)0.01
ȃMale sex1543 (53.7%)1584 (54.8%)0.021220 (54.5%)1202 (53.7%)0.02
ȃRace/ethnicity
ȃȃWhite1925 (67.0%)2008 (69.5%)0.051511 (67.5%)1514 (67.6%)0.01
ȃȃBlack400 (13.9%)386 (13.4%)0.02312 (13.9%)312 (13.9%)0.01
ȃȃHispanic60 (2.1%)48 (1.7%)0.0342 (1.9%)39 (1.7%)0.01
ȃȃAsian134 (4.7%)131 (4.5%)0.0199 (4.4%)113 (5.0%)0.01
ȃȃOther/missing352 (12.3%)318 (11.0%)0.04275 (12.3%)261 (11.7%)0.01
Hospital
ȃTertiary hospital 1822 (29%)796 (28%)0.02633 (28.3%)633 (28.3%)0.00
ȃTertiary hospital 21301 (45%)1411 (49%)0.081084 (48.4%)1084 (48.4%)0.00
ȃCommunity hospital 1384 (13%)295 (10%)0.09244 (10.9%)244 (10.9%)0.00
ȃCommunity hospital 2364 (13%)389 (14%)0.03278 (12.4%)278 (12.4%)0.00
Clinical servicea
ȃCardiac surgery8 (0.3%)11 (0.4%)0.027 (0.3%)6 (0.3%)0.02
ȃCardiology92 (3.2%)61 (2.1%)0.0753 (2.4%)58 (2.6%)0.01
ȃEmergency51 (1.8%)57 (2.0%)0.0247 (2.1%)48 (2.1%)0.02
ȃGynecology3 (0.1%)5 (0.2%)0.033 (0.1%)2 (0.1%)0.00
ȃMedicine2165 (75.8%)2029 (70.3%)0.121662 (74.2%)1626 (72.6%)0.04
ȃNeurology86 (3.0%)94 (3.3%)0.0267 (3.0%)72 (3.2%)0.00
ȃObstetrics9 (0.3%)8 (0.3%)0.005 (0.2%)7 (0.3%)0.01
ȃOncology274 (9.6%)398 (13.8%)0.13253 (11.3%)268 (12.0%)0.04
ȃSurgery127 (4.4%)182 (6.3%)0.09109 (4.9%)124 (5.6%)0.02
Comorbidities
ȃCongestive heart failure807 (28.1%)666 (23.0%)0.02582 (26.0%)569 (25.4%)0.03
ȃRenal failure759 (26.4%)734 (25.4%)0.03589 (26.3%)590 (26.4%)0.04
ȃLiver disease228 (7.9%)285 (9.9%)0.12196 (8.8%)199 (8.9%)0.01
ȃCancer577 (20.1%)713 (24.6%)0.03501 (22.4%)525 (23.4%)0.03
ȃDiabetes854 (29.7%)791 (27.4%)0.12640 (28.6%)629 (28.1%)0.02
ȃNeurological disease425 (14.8%)439 (15.2%)0.02325 (14.5%)318 (14.2%)0.01
ȃElixhauser score, mean (SD)10.8 (11.7)11.9 (12.2)0.0911.0 (12.0)11.4 (12.1)0.03
Clinical characteristics
ȃAntibiotic exposure before pneumoniab297 (10.3%)460 (15.9%)0.17272 (12.1%)296 (13.2%)0.02
ȃIntensive care exposure before pneumoniab134 (4.7%)251 (8.7%)0.16119 (5.3%)135 (6.0%)0.03
ȃHospital days before pneumoniab, mean (SD)1.3 (4.4)2.2 (6.0)0.061.5 (4.1)1.7 (4.4)0.05
ȃBlood cultures drawn1370 (47.7%)1718 (59.4%)0.241166 (52.1%)1187 (53.0%)0.01
ȃSputum cultures obtained397 (13.8%)681 (23.6%)0.25380 (17.0%)380 (17.0%)0.02
ȃSputum cultures positive92 (3.2%)176 (6.1%)0.1488 (3.9%)97 (4.3%)0.02
ȃGram positives40 (1.4%)88 (3.0%)0.1140 (1.8%)42 (1.9%)0.03
ȃEnteric gram negatives35 (1.2%)73 (2.5%)0.1034 (1.5%)41 (1.8%)0.00
ȃNonfermenters23 (0.8%)28 (1.0%)0.0219 (0.8%)22 (1.0%)0.01
ȃPositive respiratory viral assay262 (9.1)199 (6.9)0.08183 (8.2)165 (7.4)0.03
ȃVital signs
ȃȃMaximum temperature, °C, mean (SD)37.3 (0.8)37.6 (0.8)0.2937.4 (0.8)37.4 (0.8)0.00
ȃȃMedian daily respiratory rate, breaths/min, mean (SD)19.3 (2.7)19.5 (2.8)0.0719.4 (2.7)19.3 (2.6)0.04
ȃȃMaximum heart rate, beats/min, mean (SD)98.4 (20.9)101.6 (20.8)0.1599.7 (21.3)99.6 (20.5)0.01
ȃȃMedian systolic blood pressure, mm Hg, mean (SD)130.3 (21.6)127.5 (21.1)0.13128.8 (20.7)128.8 (21.5)0.00
ȃȃVasopressors first day of pneumonia29 (1.0%)50 (1.7%)0.1626 (1.2%)28 (1.3%)0.02
ȃLaboratory values, mean (SD)
ȃȃWBC count, 109 cells/L9.7 (6.8)10.8 (6.8)0.1610.0 (5.8)10.3 (5.7)0.05
ȃȃHemoglobin, g/dL11.5 (2.3)11.1 (2.3)0.0411.3 (2.4)11.3 (2.2)0.00
ȃȃHematocrit, %34.9 (6.7)33.8 (6.4)0.1734.4 (6.7)34.3 (6.3)0.02
ȃȃPlatelets, 109 cells/L233.1 (111.2)231.4 (130.4)0.01233.6 (115.9)232.9 (114.2)0.01
ȃȃCreatinine, mg/dL1.4 (1.7)1.3 (1.3)0.071.4 (1.6)1.3 (1.4)0.07
ȃȃSodium, mmol/L137.3 (4.7)137.0 (4.9)0.06137.2 (4.9)137.1 (4.8)0.02
ȃȃALT, U/L32.5 (61.3)33.7 (81.8)0.0233.3 (65.1)31.8 (47.2)0.03
ȃȃBilirubin, mg/dL0.7 (1.2)0.8 (2.2)0.060.7 (1.3)0.7 (1.3)0.00
ȃȃAlbumin, g/dL3.7 (0.6)3.6 (0.6)0.173.7 (0.6)3.7 (0.6)0.00
ȃȃINR1.2 (0.7)1.3 (0.8)0.131.2 (0.7)1.2 (0.7)0.00
ȃȃGlucose, mg/dL148.7 (83.6)153.8 (89.9)0.06150.9 (87.8)149.9 (81.4)0.01
Total CohortPropensity-Matched Cohort
Characteristic1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)Std Diff1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)Std Diff
Demographics
ȃAge, y, mean (SD)66.1 (18.2)64.9 (18.5)0.0765.4 (18.3)65.5 (18.5)0.01
ȃMale sex1543 (53.7%)1584 (54.8%)0.021220 (54.5%)1202 (53.7%)0.02
ȃRace/ethnicity
ȃȃWhite1925 (67.0%)2008 (69.5%)0.051511 (67.5%)1514 (67.6%)0.01
ȃȃBlack400 (13.9%)386 (13.4%)0.02312 (13.9%)312 (13.9%)0.01
ȃȃHispanic60 (2.1%)48 (1.7%)0.0342 (1.9%)39 (1.7%)0.01
ȃȃAsian134 (4.7%)131 (4.5%)0.0199 (4.4%)113 (5.0%)0.01
ȃȃOther/missing352 (12.3%)318 (11.0%)0.04275 (12.3%)261 (11.7%)0.01
Hospital
ȃTertiary hospital 1822 (29%)796 (28%)0.02633 (28.3%)633 (28.3%)0.00
ȃTertiary hospital 21301 (45%)1411 (49%)0.081084 (48.4%)1084 (48.4%)0.00
ȃCommunity hospital 1384 (13%)295 (10%)0.09244 (10.9%)244 (10.9%)0.00
ȃCommunity hospital 2364 (13%)389 (14%)0.03278 (12.4%)278 (12.4%)0.00
Clinical servicea
ȃCardiac surgery8 (0.3%)11 (0.4%)0.027 (0.3%)6 (0.3%)0.02
ȃCardiology92 (3.2%)61 (2.1%)0.0753 (2.4%)58 (2.6%)0.01
ȃEmergency51 (1.8%)57 (2.0%)0.0247 (2.1%)48 (2.1%)0.02
ȃGynecology3 (0.1%)5 (0.2%)0.033 (0.1%)2 (0.1%)0.00
ȃMedicine2165 (75.8%)2029 (70.3%)0.121662 (74.2%)1626 (72.6%)0.04
ȃNeurology86 (3.0%)94 (3.3%)0.0267 (3.0%)72 (3.2%)0.00
ȃObstetrics9 (0.3%)8 (0.3%)0.005 (0.2%)7 (0.3%)0.01
ȃOncology274 (9.6%)398 (13.8%)0.13253 (11.3%)268 (12.0%)0.04
ȃSurgery127 (4.4%)182 (6.3%)0.09109 (4.9%)124 (5.6%)0.02
Comorbidities
ȃCongestive heart failure807 (28.1%)666 (23.0%)0.02582 (26.0%)569 (25.4%)0.03
ȃRenal failure759 (26.4%)734 (25.4%)0.03589 (26.3%)590 (26.4%)0.04
ȃLiver disease228 (7.9%)285 (9.9%)0.12196 (8.8%)199 (8.9%)0.01
ȃCancer577 (20.1%)713 (24.6%)0.03501 (22.4%)525 (23.4%)0.03
ȃDiabetes854 (29.7%)791 (27.4%)0.12640 (28.6%)629 (28.1%)0.02
ȃNeurological disease425 (14.8%)439 (15.2%)0.02325 (14.5%)318 (14.2%)0.01
ȃElixhauser score, mean (SD)10.8 (11.7)11.9 (12.2)0.0911.0 (12.0)11.4 (12.1)0.03
Clinical characteristics
ȃAntibiotic exposure before pneumoniab297 (10.3%)460 (15.9%)0.17272 (12.1%)296 (13.2%)0.02
ȃIntensive care exposure before pneumoniab134 (4.7%)251 (8.7%)0.16119 (5.3%)135 (6.0%)0.03
ȃHospital days before pneumoniab, mean (SD)1.3 (4.4)2.2 (6.0)0.061.5 (4.1)1.7 (4.4)0.05
ȃBlood cultures drawn1370 (47.7%)1718 (59.4%)0.241166 (52.1%)1187 (53.0%)0.01
ȃSputum cultures obtained397 (13.8%)681 (23.6%)0.25380 (17.0%)380 (17.0%)0.02
ȃSputum cultures positive92 (3.2%)176 (6.1%)0.1488 (3.9%)97 (4.3%)0.02
ȃGram positives40 (1.4%)88 (3.0%)0.1140 (1.8%)42 (1.9%)0.03
ȃEnteric gram negatives35 (1.2%)73 (2.5%)0.1034 (1.5%)41 (1.8%)0.00
ȃNonfermenters23 (0.8%)28 (1.0%)0.0219 (0.8%)22 (1.0%)0.01
ȃPositive respiratory viral assay262 (9.1)199 (6.9)0.08183 (8.2)165 (7.4)0.03
ȃVital signs
ȃȃMaximum temperature, °C, mean (SD)37.3 (0.8)37.6 (0.8)0.2937.4 (0.8)37.4 (0.8)0.00
ȃȃMedian daily respiratory rate, breaths/min, mean (SD)19.3 (2.7)19.5 (2.8)0.0719.4 (2.7)19.3 (2.6)0.04
ȃȃMaximum heart rate, beats/min, mean (SD)98.4 (20.9)101.6 (20.8)0.1599.7 (21.3)99.6 (20.5)0.01
ȃȃMedian systolic blood pressure, mm Hg, mean (SD)130.3 (21.6)127.5 (21.1)0.13128.8 (20.7)128.8 (21.5)0.00
ȃȃVasopressors first day of pneumonia29 (1.0%)50 (1.7%)0.1626 (1.2%)28 (1.3%)0.02
ȃLaboratory values, mean (SD)
ȃȃWBC count, 109 cells/L9.7 (6.8)10.8 (6.8)0.1610.0 (5.8)10.3 (5.7)0.05
ȃȃHemoglobin, g/dL11.5 (2.3)11.1 (2.3)0.0411.3 (2.4)11.3 (2.2)0.00
ȃȃHematocrit, %34.9 (6.7)33.8 (6.4)0.1734.4 (6.7)34.3 (6.3)0.02
ȃȃPlatelets, 109 cells/L233.1 (111.2)231.4 (130.4)0.01233.6 (115.9)232.9 (114.2)0.01
ȃȃCreatinine, mg/dL1.4 (1.7)1.3 (1.3)0.071.4 (1.6)1.3 (1.4)0.07
ȃȃSodium, mmol/L137.3 (4.7)137.0 (4.9)0.06137.2 (4.9)137.1 (4.8)0.02
ȃȃALT, U/L32.5 (61.3)33.7 (81.8)0.0233.3 (65.1)31.8 (47.2)0.03
ȃȃBilirubin, mg/dL0.7 (1.2)0.8 (2.2)0.060.7 (1.3)0.7 (1.3)0.00
ȃȃAlbumin, g/dL3.7 (0.6)3.6 (0.6)0.173.7 (0.6)3.7 (0.6)0.00
ȃȃINR1.2 (0.7)1.3 (0.8)0.131.2 (0.7)1.2 (0.7)0.00
ȃȃGlucose, mg/dL148.7 (83.6)153.8 (89.9)0.06150.9 (87.8)149.9 (81.4)0.01

Data are presented as No. (%) unless otherwise indicated.

Abbreviations: ALT, alanine aminotransferase; INR, international normalized ratio; SD, standard deviation; Std Diff, standardized difference; WBC, white blood cell.

Clinical service on hospital day 2.

Exposures measured prior to the first day of antibiotics with a stated indication of pneumonia.

Outcomes

Absolute outcomes for both the total cohort and the propensity-matched subset are shown in Table 2 and measures of association for propensity-matched patients treated with 1–2 vs 5–8 days of antibiotics are shown in Table 3. There were no statistically significant differences in hospital mortality (2.1% vs 2.8%, SHR, 0.75 [95% CI, .51–1.09]) but the SHR for time to discharge alive was significantly higher for patients treated with 1–2 days of antibiotics (ie, they were discharged sooner; mean days to discharge, 6.1 vs 6.6; SHR, 1.13 [95% CI, 1.07–1.19]) and they had slightly more 30-day hospital-free days (23.1 vs 22.7; mean difference, 0.44 [95% CI, .09–.78]). There were no significant differences in 30-day readmissions (16.0% vs 15.8%; OR, 1.01 [95% CI, .86–1.19]), 30-day mortality (4.6% vs 5.1%; OR, 0.91 [95% CI, .69–1.19]), or 90-day C. difficile infections (1.3% vs 0.8%; OR, 1.67 [95% CI, .94–2.99]). However, patients treated for 1–2 days had 4.4 more antibiotic-free days alive (25.9 vs 21.5; mean difference, 95% CI, 4.08–4.69) compared to those treated with 5–8 days of antibiotics.

Table 2.
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Comparative Outcomes Among Hospitalized Patients Treated With 1–2 Days Versus 5–8 Days of Antibiotics for Possible Pneumonia Who Had Oxygen Saturations ≥95% on Ambient Air

OutcomeTotal CohortPropensity-Matched Cohort
1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)P Value1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)P Value
Antibiotic daysa1.31 (0.5)6.3 (1.1)<.0011.3 (0.5)6.2 (1.1)<.001
Antibiotic-free daysb26.1 (5.7)21.5 (4.9)<.00125.9 (5.9)21.5 (4.8)<.001
Hospital days until dischargec6.1 (7.5)7.0 (7.9)<.0016.1 (7.7)6.6 (7.1).04
Hospital days, total7.4 (9.2)9.2 (11.2)<.0017.6 (9.3)8.3 (9.0).01
Hospital-free daysb23.2 (6.0)22.4 (6.2)<.00123.1 (6.1)22.7 (5.9).02
Hospital death, count (%)58 (2.0%)87 (3.0%).0247 (2.1%)63 (2.8%).15
30-day mortality, count (%)127 (4.4%)161 (5.6%).05104 (4.6%)114 (5.1%).53
30-day readmission, count (%)438 (15.3%)453 (15.7%).69358 (16.0%)354 (15.8%).90
Clostridioides difficile toxin positive within 90 days, count (%)33 (1.1%)24 (0.8%).2730 (1.3%)18 (0.8%).11
OutcomeTotal CohortPropensity-Matched Cohort
1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)P Value1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)P Value
Antibiotic daysa1.31 (0.5)6.3 (1.1)<.0011.3 (0.5)6.2 (1.1)<.001
Antibiotic-free daysb26.1 (5.7)21.5 (4.9)<.00125.9 (5.9)21.5 (4.8)<.001
Hospital days until dischargec6.1 (7.5)7.0 (7.9)<.0016.1 (7.7)6.6 (7.1).04
Hospital days, total7.4 (9.2)9.2 (11.2)<.0017.6 (9.3)8.3 (9.0).01
Hospital-free daysb23.2 (6.0)22.4 (6.2)<.00123.1 (6.1)22.7 (5.9).02
Hospital death, count (%)58 (2.0%)87 (3.0%).0247 (2.1%)63 (2.8%).15
30-day mortality, count (%)127 (4.4%)161 (5.6%).05104 (4.6%)114 (5.1%).53
30-day readmission, count (%)438 (15.3%)453 (15.7%).69358 (16.0%)354 (15.8%).90
Clostridioides difficile toxin positive within 90 days, count (%)33 (1.1%)24 (0.8%).2730 (1.3%)18 (0.8%).11

Data are presented as mean (standard deviation) unless otherwise indicated.

Includes both inpatient antibiotics and discharge antibiotics.

Within 30 days of the first day of antibiotics.

Measured from the first day of antibiotics for pneumonia.

Table 2.
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Comparative Outcomes Among Hospitalized Patients Treated With 1–2 Days Versus 5–8 Days of Antibiotics for Possible Pneumonia Who Had Oxygen Saturations ≥95% on Ambient Air

OutcomeTotal CohortPropensity-Matched Cohort
1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)P Value1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)P Value
Antibiotic daysa1.31 (0.5)6.3 (1.1)<.0011.3 (0.5)6.2 (1.1)<.001
Antibiotic-free daysb26.1 (5.7)21.5 (4.9)<.00125.9 (5.9)21.5 (4.8)<.001
Hospital days until dischargec6.1 (7.5)7.0 (7.9)<.0016.1 (7.7)6.6 (7.1).04
Hospital days, total7.4 (9.2)9.2 (11.2)<.0017.6 (9.3)8.3 (9.0).01
Hospital-free daysb23.2 (6.0)22.4 (6.2)<.00123.1 (6.1)22.7 (5.9).02
Hospital death, count (%)58 (2.0%)87 (3.0%).0247 (2.1%)63 (2.8%).15
30-day mortality, count (%)127 (4.4%)161 (5.6%).05104 (4.6%)114 (5.1%).53
30-day readmission, count (%)438 (15.3%)453 (15.7%).69358 (16.0%)354 (15.8%).90
Clostridioides difficile toxin positive within 90 days, count (%)33 (1.1%)24 (0.8%).2730 (1.3%)18 (0.8%).11
OutcomeTotal CohortPropensity-Matched Cohort
1–2 Days of Antibiotics (n = 2871)5–8 Days of Antibiotics (n = 2891)P Value1–2 Days of Antibiotics (n = 2239)5–8 Days of Antibiotics (n = 2239)P Value
Antibiotic daysa1.31 (0.5)6.3 (1.1)<.0011.3 (0.5)6.2 (1.1)<.001
Antibiotic-free daysb26.1 (5.7)21.5 (4.9)<.00125.9 (5.9)21.5 (4.8)<.001
Hospital days until dischargec6.1 (7.5)7.0 (7.9)<.0016.1 (7.7)6.6 (7.1).04
Hospital days, total7.4 (9.2)9.2 (11.2)<.0017.6 (9.3)8.3 (9.0).01
Hospital-free daysb23.2 (6.0)22.4 (6.2)<.00123.1 (6.1)22.7 (5.9).02
Hospital death, count (%)58 (2.0%)87 (3.0%).0247 (2.1%)63 (2.8%).15
30-day mortality, count (%)127 (4.4%)161 (5.6%).05104 (4.6%)114 (5.1%).53
30-day readmission, count (%)438 (15.3%)453 (15.7%).69358 (16.0%)354 (15.8%).90
Clostridioides difficile toxin positive within 90 days, count (%)33 (1.1%)24 (0.8%).2730 (1.3%)18 (0.8%).11

Data are presented as mean (standard deviation) unless otherwise indicated.

Includes both inpatient antibiotics and discharge antibiotics.

Within 30 days of the first day of antibiotics.

Measured from the first day of antibiotics for pneumonia.

Table 3.
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Overall and Subgroup Outcome Comparisons of Patients Treated With Very Short Courses (1–2 Days) Matched to Patients Treated With Conventional Courses (5–8 Days) of Antibiotics for Possible Pneumonia With Oxygen Saturations ≥95% on Ambient Air

OutcomeMeasure of AssociationAll Patients (N = 4478)CAP (n = 3466)HAP (n = 746)Sputum Cultures Obtained (n = 712)Discharge Diagnosis Code for Pneumonia (n = 1104)
In-hospital deathSHR0.75 (.51–1.09)0.76 (.47–1.23)1.08 (.53–2.21)0.83 (.25–2.74)1.61 (.72–3.57)
Hospital dischargeSHR1.13 (1.07–1.19)1.14 (1.07–1.21)1.09 (.95–1.25)1.14 (1.00–1.31)1.11 (1.00–1.23)
Readmission within 30 daysOdds ratio1.01 (.86–1.19)1.04 (.86–1.25)1.09 (.76–1.58)0.79 (.51–1.21)0.96 (.68–1.34)
30-day deathsOdds ratio0.91 (.69–1.19)0.84 (.60–1.18)1.38 (.81–2.36)1.00 (.45–2.22)1.09 (.61–1.95)
Hospital-free daysMean difference0.44 (.09–.78)0.38 (.00–.76)0.57 (−.49 to 1.62)0.49 (−.33 to 1.32)0.48 (−.22 to 1.18)
Clostridioides difficile within 90 daysOdds ratio1.67 (.94–2.99)1.42 (.67–2.99)3.07 (.97–9.70)2.01 (.36–11.15)1.51 (.42–5.40)
Antibiotic daysMean difference−4.92 (−4.97 to −4.87)−4.90 (−4.96 to −4.85)−4.94 (−5.07 to −4.81)−4.87 (−5.00 to −4.74)−4.84 (−4.94 to −4.74)
Antibiotic-free daysMean difference4.38 (4.08–4.69)4.58 (4.26–4.90)2.24 (1.23–3.25)3.44 (2.69–4.18)3.25 (2.69–3.81)
OutcomeMeasure of AssociationAll Patients (N = 4478)CAP (n = 3466)HAP (n = 746)Sputum Cultures Obtained (n = 712)Discharge Diagnosis Code for Pneumonia (n = 1104)
In-hospital deathSHR0.75 (.51–1.09)0.76 (.47–1.23)1.08 (.53–2.21)0.83 (.25–2.74)1.61 (.72–3.57)
Hospital dischargeSHR1.13 (1.07–1.19)1.14 (1.07–1.21)1.09 (.95–1.25)1.14 (1.00–1.31)1.11 (1.00–1.23)
Readmission within 30 daysOdds ratio1.01 (.86–1.19)1.04 (.86–1.25)1.09 (.76–1.58)0.79 (.51–1.21)0.96 (.68–1.34)
30-day deathsOdds ratio0.91 (.69–1.19)0.84 (.60–1.18)1.38 (.81–2.36)1.00 (.45–2.22)1.09 (.61–1.95)
Hospital-free daysMean difference0.44 (.09–.78)0.38 (.00–.76)0.57 (−.49 to 1.62)0.49 (−.33 to 1.32)0.48 (−.22 to 1.18)
Clostridioides difficile within 90 daysOdds ratio1.67 (.94–2.99)1.42 (.67–2.99)3.07 (.97–9.70)2.01 (.36–11.15)1.51 (.42–5.40)
Antibiotic daysMean difference−4.92 (−4.97 to −4.87)−4.90 (−4.96 to −4.85)−4.94 (−5.07 to −4.81)−4.87 (−5.00 to −4.74)−4.84 (−4.94 to −4.74)
Antibiotic-free daysMean difference4.38 (4.08–4.69)4.58 (4.26–4.90)2.24 (1.23–3.25)3.44 (2.69–4.18)3.25 (2.69–3.81)

Data in parentheses indicate the 95% confidence interval.

Abbreviations: CAP, community-acquired pneumonia; HAP, hospital-acquired pneumonia; SHR, subdistribution hazard ratio.

Table 3.
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Overall and Subgroup Outcome Comparisons of Patients Treated With Very Short Courses (1–2 Days) Matched to Patients Treated With Conventional Courses (5–8 Days) of Antibiotics for Possible Pneumonia With Oxygen Saturations ≥95% on Ambient Air

OutcomeMeasure of AssociationAll Patients (N = 4478)CAP (n = 3466)HAP (n = 746)Sputum Cultures Obtained (n = 712)Discharge Diagnosis Code for Pneumonia (n = 1104)
In-hospital deathSHR0.75 (.51–1.09)0.76 (.47–1.23)1.08 (.53–2.21)0.83 (.25–2.74)1.61 (.72–3.57)
Hospital dischargeSHR1.13 (1.07–1.19)1.14 (1.07–1.21)1.09 (.95–1.25)1.14 (1.00–1.31)1.11 (1.00–1.23)
Readmission within 30 daysOdds ratio1.01 (.86–1.19)1.04 (.86–1.25)1.09 (.76–1.58)0.79 (.51–1.21)0.96 (.68–1.34)
30-day deathsOdds ratio0.91 (.69–1.19)0.84 (.60–1.18)1.38 (.81–2.36)1.00 (.45–2.22)1.09 (.61–1.95)
Hospital-free daysMean difference0.44 (.09–.78)0.38 (.00–.76)0.57 (−.49 to 1.62)0.49 (−.33 to 1.32)0.48 (−.22 to 1.18)
Clostridioides difficile within 90 daysOdds ratio1.67 (.94–2.99)1.42 (.67–2.99)3.07 (.97–9.70)2.01 (.36–11.15)1.51 (.42–5.40)
Antibiotic daysMean difference−4.92 (−4.97 to −4.87)−4.90 (−4.96 to −4.85)−4.94 (−5.07 to −4.81)−4.87 (−5.00 to −4.74)−4.84 (−4.94 to −4.74)
Antibiotic-free daysMean difference4.38 (4.08–4.69)4.58 (4.26–4.90)2.24 (1.23–3.25)3.44 (2.69–4.18)3.25 (2.69–3.81)
OutcomeMeasure of AssociationAll Patients (N = 4478)CAP (n = 3466)HAP (n = 746)Sputum Cultures Obtained (n = 712)Discharge Diagnosis Code for Pneumonia (n = 1104)
In-hospital deathSHR0.75 (.51–1.09)0.76 (.47–1.23)1.08 (.53–2.21)0.83 (.25–2.74)1.61 (.72–3.57)
Hospital dischargeSHR1.13 (1.07–1.19)1.14 (1.07–1.21)1.09 (.95–1.25)1.14 (1.00–1.31)1.11 (1.00–1.23)
Readmission within 30 daysOdds ratio1.01 (.86–1.19)1.04 (.86–1.25)1.09 (.76–1.58)0.79 (.51–1.21)0.96 (.68–1.34)
30-day deathsOdds ratio0.91 (.69–1.19)0.84 (.60–1.18)1.38 (.81–2.36)1.00 (.45–2.22)1.09 (.61–1.95)
Hospital-free daysMean difference0.44 (.09–.78)0.38 (.00–.76)0.57 (−.49 to 1.62)0.49 (−.33 to 1.32)0.48 (−.22 to 1.18)
Clostridioides difficile within 90 daysOdds ratio1.67 (.94–2.99)1.42 (.67–2.99)3.07 (.97–9.70)2.01 (.36–11.15)1.51 (.42–5.40)
Antibiotic daysMean difference−4.92 (−4.97 to −4.87)−4.90 (−4.96 to −4.85)−4.94 (−5.07 to −4.81)−4.87 (−5.00 to −4.74)−4.84 (−4.94 to −4.74)
Antibiotic-free daysMean difference4.38 (4.08–4.69)4.58 (4.26–4.90)2.24 (1.23–3.25)3.44 (2.69–4.18)3.25 (2.69–3.81)

Data in parentheses indicate the 95% confidence interval.

Abbreviations: CAP, community-acquired pneumonia; HAP, hospital-acquired pneumonia; SHR, subdistribution hazard ratio.

Subgroup Analyses

Measures of association were largely consistent in all subgroup analyses (Table 3). Short courses were associated with higher hazards for hospital discharge (ie, less time to discharge) among patients treated for community-acquired pneumonia, those in whom sputum cultures were obtained, and patients with discharge diagnosis codes for pneumonia, but were not significant for those with hospital-acquired pneumonia. There were no significant differences in hospital deaths, readmissions, 30-day deaths, hospital-free days, or C. difficile infections between short vs conventional courses in any of the subgroups. Antibiotic-free days were significantly higher for patients treated with 1–2 days of antibiotics in all subgroups. When patients were propensity-matched using clinical parameters from the second day of antibiotics rather than from the first day of antibiotics, results were consistent with the primary analysis.

DISCUSSION

In this large propensity-matched analysis, we did not detect any statistically significant differences in mortality or readmissions among patients treated for possible pneumonia who had oxygen saturations ≥95% without supplemental oxygen regardless of whether they were treated with 1–2 days of antibiotics vs 5–8 days of antibiotics. Our findings suggest that deliberate review of oxygenation levels may be a practical strategy to help clinicians identify patients on antibiotics for possible pneumonia who are promising candidates for early discontinuation of antibiotics.

The lack of apparent benefit of conventional antibiotic course durations for patients with possible pneumonia but preserved oxygenation likely reflects a combination of factors. Some patients may not have had pneumonia at all, a frequent phenomenon in the hospitalized population given the nonspecific nature of the clinical symptoms, signs, laboratory tests, and radiographs used to diagnose pneumonia [6–11]. Other patients may have had pneumonia but with a viral rather than a bacterial etiology. One-third to one-half of community-acquired pneumonias in hospitalized patients and one-fifth of hospital-acquired pneumonias are attributable to viruses [29–31]. A further set of patients may indeed have had bacterial pneumonia but mild cases with minimal parenchymal invasion and/or very good physiologic reserves as suggested by their preserved oxygenation levels, such that they were able to recover with very brief treatment courses.

Our results are compatible with the growing literature demonstrating the safety of brief antibiotic courses for community-acquired pneumonia. Two randomized trials comparing the safety of 3 vs 8 days of antibiotics for patients hospitalized with moderate to severe pneumonia reported no differences in outcomes between groups [32, 33]. A third trial reported a similar finding among ventilated patients with pulmonary infiltrates and low clinical pulmonary infection scores who were randomized to stopping antibiotics after 3 days vs usual care [22]. Our study builds upon these trials by demonstrating the generalizability of these findings to real-world populations without the enrollment exclusion criteria applied in these trials, the potential utility of using oxygenation levels to identify candidates for early discontinuation of antibiotics, and the potential safety of stopping antibiotics after <3 days among the subset of patients with suspected pneumonia but preserved oxygenation levels.

Limitations of our study include the observational design and thus the possibility of unmeasured confounding by indication. Clinicians may have been more likely to stop antibiotics early in patients who appeared to be more stable or in whom other information emerged that pointed to a nonbacterial or noninfectious process. We attempted to control for confounding by indication, however, by propensity-matching patients using an extensive array of clinically detailed variables including patients’ demographics, comorbidities, vital signs, laboratory values, bacterial and viral testing, and prior treatments. Despite the large number and granularity of the clinical parameters included in our propensity scores, we were able to achieve a close match without a large loss in sample size. Indeed, it is notable that even before matching, patients were almost perfectly divided into short course and conventional course groups with small standardized differences for the majority of patient characteristics. This suggests there is some degree of clinical equipoise at the bedside as to whether patients with possible pneumonia but preserved oxygen saturations need antibiotics or not. Nonetheless, the finding that patients treated with shorter courses may have been discharged sooner may be due to residual confounding.

Other limitations of our study include our focus on 4 hospitals from a single region of one country. This may limit generalizability. It is also possible that treating clinicians misspecified indications for some patients, leading to contamination of the study sample with patients without pneumonia. Prior validation studies, however, have suggested that the indications provided by clinicians when they prescribe antibiotics accurately reflect their clinical impressions at the time of specification [10, 23]. In addition, results were consistent in the sensitivity analyses restricted to patients with a higher probability of having true pneumonia, namely those with positive sputum cultures and those with discharge diagnosis codes for pneumonia. Postdischarge antibiotic durations were calculated from discharge prescriptions but may not reflect what patients took if patients failed to fill prescriptions, stopped their courses early, or received extensions from their providers. Finally, propensity score matching does not accommodate time-varying confounders that are affected by past treatment; for example, some residual bias in our estimates is possible if time-updated laboratory measures or vital signs suggesting disease progression affected clinicians’ decisions to stop or continue antibiotics and were also, themselves, affected by past antibiotic decisions [34]. Our findings were consistent on a sensitivity analysis where we used patients’ clinical parameters on the second day of treatment rather than the first, but bias may still occur even when such measures are included in the propensity score model. Emerging causal inference methods can better accommodate these more complex data interactions and are a promising route for future observational studies of time-varying treatment strategies [35].

In summary, we found no evidence of harm, and possible benefit, with 1–2 vs 5–8 days of antibiotics to treat possible pneumonia in patients who had oxygen saturations ≥95% on ambient air. This analysis suggests a potentially powerful strategy to help clinicians to easily identify a subset of patients with possible pneumonia in whom early discontinuation of antibiotics may be safe. The potential population that could benefit from this strategy is large. Our study and others suggest that a quarter to a third of hospitalized patients treated for possible pneumonia may fall into this category [10, 20, 21]. Early discontinuation of antibiotics started for possible pneumonia in hospitalized patients with normal oxygenation merits testing in a prospective randomized trial to confirm or refute the feasibility, safety, and utility of this strategy for reducing unnecessary antibiotic use.

Notes

Financial support. This work was supported by the Prevention Epicenters Program of the Centers for Disease Control and Prevention.

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Author notes

Potential conflicts of interest. M. K. has received royalties from UpToDate for articles on pneumonia and has also received grants from the Agency for Healthcare Research and Quality. C. R. has received royalties from UpToDate for articles on procalcitonin; payments for consulting related to sepsis diagnostics from Cytovale; and payments from Pfizer for consulting related to Lyme disease surveillance. All other authors report no potential conflicts.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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1 Comment
Comments (1)
No radiographic criteria nor information whatsoever for these reported "pneumonia" patients
19 August 2022
Bruce L Davidson MD MPH
Washington State University Floyd College of Medicine
These authors' Discussion asserts, "Our results are compatible with the growing literature demonstrating the safety of brief antibiotic courses for community-acquired pneumonia". Yet within the "granular clinical data" extracted (Methods) including serum bilirubin levels, there is zero in this report confirming presence of any, let alone suspicious, radiographic infiltrate(s). From Murray & Nadel's 7th edition Respiratory Medicine text: "Radiologic evaluation is required to establish the presence of pneumonia, because there is no combination of historical data, physical findings, or laboratory results that reliably confirms the diagnosis."
So an Emergency Dept NP or PA or busy shift hospitalist typing "pneumonia" in order to start antimicrobial therapy was sufficient for study entry. Pneumonia patients with positive blood cultures (bacteremia) were specifically excluded! The authors promote a clinical trial of their O2 saturation <95% criterion.
Early pneumonia in patients with good pulmonary reserve may present with preserved O2 saturation due to hyperventilation. Tuberculous pneumonia in early HIV-infected patients and others and minimally symptomatic or asymptomatic fungal (histoplasma, coccidioides) pneumonias may each present to ED with O2 saturation >95%. Each such patient requires radiologic imaging and a differential diagnosis.
For decades it has been the standard for studies of patients with suspected pneumonia to have at least a single radiographic infiltrate, albeit of indeterminate duration, to qualify for study entry. Rather than inspect radiology reports and a statistical sample of their study patients radiographic images, these seven authors, on behalf of our CDC, instead jettison this fundamental and essential radiologic criterion and declare "prospective trials" of their finding are warranted. They promote a 1-2 day "antibiotic" course for treating an electronic medical record "pneumonia" entry. Instead, clinicians should fully evaluate and treat the patient with possible pneumonia.
Submitted on 19/08/2022 12:41 PM GMT