Lukas Stulik1,2, Jana Hudcova3, Donald E Craven4, Gabor Nagy1,2, Eszter Nagy1,2. 1. Arsanis Biosciences GmbH, Vienna, Austria. 2. Arsanis, Inc, Waltham, MA, USA. 3. Department of Surgical Critical Care, Lahey Hospital and Medical Center, Burlington, MA, USA. 4. Infectious Diseases, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA.
Abstract
Background: Airway-colonization by Staphylococcus aureus predisposes to the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). Despite extensive antibiotic treatment of intensive care unit patients, limited data are available on the efficacy of antibiotics on bacterial airway colonization and/or prevention of infections. Therefore, microbiologic responses to antibiotic treatment were evaluated in ventilated patients. Methods: Results of semiquantitative analyses of S. aureus burden in serial endotracheal-aspirate (ETA) samples and VAT/VAP diagnosis were correlated to antibiotic treatment. Minimum inhibitory concentrations of relevant antibiotics using serially collected isolates were evaluated. Results: Forty-eight mechanically ventilated patients who were S. aureus positive by ETA samples and treated with relevant antibiotics for at least 2 consecutive days were included in the study. Vancomycin failed to reduce methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) burden in the airways. Oxacillin was ineffective for MSSA colonization in approximately 30% of the patients, and responders were typically coadministered additional antibiotics. Despite antibiotic exposure, 15 of the 39 patients (approximately 38%) colonized only by S. aureus and treated with appropriate antibiotic for at least 2 days still progressed to VAP. Importantly, no change in antibiotic susceptibility of S. aureus isolates was observed during treatment. Staphylococcus aureus colonization levels inversely correlated with the presence of normal respiratory flora. Conclusions: Antibiotic treatment is ineffective in reducing S. aureus colonization in the lower airways and preventing VAT or VAP. Staphylococcus aureus is in competition for colonization with the normal respiratory flora. To improve patient outcomes, alternatives to antibiotics are urgently needed.
Background: Airway-colonization by Staphylococcus aureus predisposes to the development of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). Despite extensive antibiotic treatment of intensive care unit patients, limited data are available on the efficacy of antibiotics on bacterial airway colonization and/or prevention of infections. Therefore, microbiologic responses to antibiotic treatment were evaluated in ventilated patients. Methods: Results of semiquantitative analyses of S. aureus burden in serial endotracheal-aspirate (ETA) samples and VAT/VAP diagnosis were correlated to antibiotic treatment. Minimum inhibitory concentrations of relevant antibiotics using serially collected isolates were evaluated. Results: Forty-eight mechanically ventilated patients who were S. aureus positive by ETA samples and treated with relevant antibiotics for at least 2 consecutive days were included in the study. Vancomycin failed to reduce methicillin-resistant S. aureus (MRSA) or methicillin-susceptible S. aureus (MSSA) burden in the airways. Oxacillin was ineffective for MSSA colonization in approximately 30% of the patients, and responders were typically coadministered additional antibiotics. Despite antibiotic exposure, 15 of the 39 patients (approximately 38%) colonized only by S. aureus and treated with appropriate antibiotic for at least 2 days still progressed to VAP. Importantly, no change in antibiotic susceptibility of S. aureus isolates was observed during treatment. Staphylococcus aureus colonization levels inversely correlated with the presence of normal respiratory flora. Conclusions: Antibiotic treatment is ineffective in reducing S. aureus colonization in the lower airways and preventing VAT or VAP. Staphylococcus aureus is in competition for colonization with the normal respiratory flora. To improve patient outcomes, alternatives to antibiotics are urgently needed.
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