Background: Up to 40% of inpatients started on antibiotics for suspected infection have negative cultures from all tested body sites. The optimal duration of treatment for these patients is unknown.
Methods: Adults admitted to 111 hospitals between 2009-2015 with clinically-suspected serious infection but negative cultures were identified. We deemed patients to have clinically-suspected serious infection if blood cultures were drawn on hospital day 1 or 2 and IV or PO antibiotics were initiated on the day of or after blood culture draw and continued for ≥ 3 days. We compared outcomes for patients treated with 3-4 vs ≥5 days of antibiotics. We excluded patients on vasopressors beyond day 2. We calculated odds ratios for in-hospital mortality (including discharge to hospice), C. difficile infection (CDI), subsequent sepsis, and antibiotic restarts >1 day after discontinuation using logistic regression, adjusting for age, race, Sequential Organ Failure Assessment (SOFA) Score, and several co-morbidities; findings were confirmed by determining the average treatment effect on the treated (ATET) using propensity matching.
Results: We identified 179,421 patients with clinically-suspected serious infection. Of these, 71,786 (40%) had all negative cultures; 26,437 (37%) were treated with 3-4 days of antibiotics and 45,349 (63%) were treated with ≥5 days. Patients treated with shorter courses were younger, had lower SOFA scores, and were less likely to have concomitant sepsis. There was no difference in mortality for short vs. long course treatment (4.7% vs 6.5%, aOR 1.01 [95% CI 0.93-1.11]; ATET=1.002 [0.998-1.006]; p=0.46). Patients treated with short courses were less likely to develop CDI (aOR 0.55 [0.47-0.66]) or subsequent sepsis (aOR 0.26, 0.17-0.41) but more likely to have antibiotic restarts (3.9% vs 3.6% aOR 1.53 [1.35-1.73]). Mortality was lower, however, amongst patients with antibiotic restarts who initially received short (vs long) courses (aOR 0.76 [0.57-1.00]).
Conclusion: We found no difference in mortality for patients with culture-negative clinically suspected serious infection treated with 3-4 days vs ≥5 days. Patients treated with short courses had less CDI and sepsis after discontinuation of antibiotics but higher rates of antibiotic restarts. A randomized controlled trial is warranted to confirm or refute these findings.
S. S. Kadri,
S. Gandra, None
C. Rhee, None
M. Klompas, None
R. Laxminarayan, Merck: Board Member , Educational grant .
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