Time to First Culture Positivity for Gram-Negative Rods Resistant to Ceftriaxone in Critically Ill Adults

Background: The optimal timing for the de-escalation of broad-spectrum antibiotics with activity against Pseudomonas aeruginosa and resistant Gram-negative rods (GNRs) in critically ill adults remains unknown. Research Question: We tested the hypothesis that cultures will identify GNRs that ultimately demonstrate resistance to ceftriaxone within 48 hours, potentially allowing safe de-escalation at this time point. Study Design and Methods: We conducted a secondary analysis of data from the Isotonic Solutions and Major Adverse Renal Events Trial: a pragmatic, cluster-randomized, multiple-crossover trial comparing balanced crystalloids versus saline for intravenous fluid administration in 15,802 critically ill adults at 5 intensive care units (ICUs) at Vanderbilt University Medical Center in Nashville, TN, USA. The primary endpoint was the time-to-positivity of respiratory and blood cultures that ultimately demonstrated growth of GNRs resistant to ceftriaxone. Multivariable logistic regression modeling was used to examine risk factors for the growth of cultures after 48 hours. Results: A total of 524 respiratory cultures had growth of GNRs, of which 284 (54.2%) had resistance to ceftriaxone. A total of 376 blood cultures grew GNRs, of which 70 (18.6%) had resistance to ceftriaxone. At 48 hours, 87% of respiratory cultures and 85% of blood cultures that ultimately grew GNRs resistant to ceftriaxone had demonstrated growth. Age, gender, predicted risk of inpatient mortality and prior use of antibiotics did not predict the growth of cultures after 48 hours. Interpretation: Among a cohort of critically ill adults, 13% of respiratory cultures and 15% of blood cultures that ultimately grew GNRs resistant to ceftriaxone did not demonstrate growth until at least 48 hours after collection. Further work is needed to determine the ideal time for critically ill adults to de-escalate from broad-spectrum antibiotics targeting Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing gram-negative pathogens.

[1]  T. Rice,et al.  Time to First Culture Positivity Among Critically Ill Adults With Methicillin-Resistant Staphylococcus aureus Growth in Respiratory or Blood Cultures , 2020, The Annals of pharmacotherapy.

[2]  M. Fine,et al.  Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America , 2019, American journal of respiratory and critical care medicine.

[3]  M. Vollmer,et al.  Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[4]  L. Visser,et al.  Time to positivity of blood cultures supports early re-evaluation of empiric broad-spectrum antimicrobial therapy , 2019, PloS one.

[5]  Jesse M. Ehrenfeld,et al.  Balanced Crystalloids versus Saline in Critically Ill Adults , 2018, Journal Club AINS.

[6]  D. Spandidos,et al.  Major pathogen microorganisms except yeasts can be detected from blood cultures within the first three days of incubation: A two-year study from a University Hospital , 2017, Experimental and therapeutic medicine.

[7]  W. Self,et al.  Influence of Antibiotics on the Detection of Bacteria by Culture-Based and Culture-Independent Diagnostic Tests in Patients Hospitalized With Community-Acquired Pneumonia , 2017, Open forum infectious diseases.

[8]  V. Luther,et al.  Frequency of empiric antibiotic de-escalation in an acute care hospital with an established Antimicrobial Stewardship Program , 2016, BMC Infectious Diseases.

[9]  J. Garnacho-Montero,et al.  Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality , 2015, Critical Care.

[10]  Arjun Srinivasan,et al.  Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[11]  J. Timsit,et al.  De-escalation as a potential way of reducing antibiotic use and antimicrobial resistance in ICU , 2014, Intensive Care Medicine.

[12]  R. Ramphal,et al.  Time to Positivity of Blood Cultures Supports Antibiotic De-escalation at 48 Hours , 2014, The Annals of pharmacotherapy.

[13]  Frédérique Jacobs,et al.  Antibiotic strategies in severe nosocomial sepsis: Why do we not de-escalate more often?* , 2012, Critical care medicine.

[14]  Dirk Vogelaers,et al.  The rising problem of antimicrobial resistance in the intensive care unit , 2011, Annals of intensive care.

[15]  L. Tsu,et al.  Practice patterns for antibiotic de-escalation in culture-negative healthcare-associated pneumonia , 2010, Infection.

[16]  Á. Atallah,et al.  De-escalation of antimicrobial treatment for adults with sepsis, severe sepsis or septic shock. , 2010, The Cochrane database of systematic reviews.

[17]  Claude D Martin,et al.  Ventilator-associated pneumonia: Breaking the vicious circle of antibiotic overuse* , 2007, Critical care medicine.

[18]  M. Niederman.  De-escalation therapy in ventilator-associated pneumonia , 2006, Current opinion in critical care.

[19]  L. Rice,et al.  Empirical antibiotic choice for the seriously ill patient: are minimization of selection of resistant organisms and maximization of individual outcome mutually exclusive? , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  M. Niederman,et al.  Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU. , 2002, Chest.

[21]  G Sherman,et al.  The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. , 2000, Chest.

[22]  G Sherman,et al.  Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. , 1999, Chest.