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.

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Efficacy and Safety of Once-Daily Amikacin in Combination with Ceftazidime in Critically Ill Adults with Severe Gram-Negative Infections

Journal of Chemotherapy ◽

10.1179/joc.1996.8.6.457 ◽

1996 ◽

Vol 8 (6) ◽

pp. 457-464 ◽

Cited By ~ 6

Author(s):

D.F. Fayed ◽

N.S. Dahmash ◽

A.H. Al-Zeer ◽

A.M. Shibl ◽

S.O. Huraib ◽

...

Keyword(s):

Critically Ill ◽

Efficacy And Safety ◽

Once Daily ◽

Gram Negative ◽

Critically Ill Adults ◽

Ill Adults

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Time to First Culture Positivity Among Critically Ill Adults With Methicillin-Resistant Staphylococcus aureus Growth in Respiratory or Blood Cultures

Annals of Pharmacotherapy ◽

10.1177/1060028019877937 ◽

2019 ◽

Vol 54 (2) ◽

pp. 131-137 ◽

Cited By ~ 1

Author(s):

Paige A. Melling ◽

Michael J. Noto ◽

Todd W. Rice ◽

Matthew W. Semler ◽

Joanna L. Stollings

Keyword(s):

Staphylococcus Aureus ◽

Critically Ill ◽

Methicillin Resistant Staphylococcus Aureus ◽

Blood Cultures ◽

Gram Stain ◽

Gram Positive ◽

Patient Admissions ◽

Critically Ill Adults ◽

Ill Adults ◽

Gram Positive Cocci

Background: For critically ill adults receiving empirical vancomycin, the duration of negative cultures after which vancomycin may be discontinued without risking subsequent growth of methicillin-resistant Staphylococcus aureus (MRSA) remains unknown. Objective: We hypothesized that if sputum cultures did not grow MRSA or blood cultures did not grow Gram-positive cocci on Gram stain by 48 hours, those cultures would not subsequently demonstrate MRSA. Methods: We conducted an ancillary analysis from patients enrolled in the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). In this cohort of patients, we collected data on the time of either MRSA identification in culture or Gram-positive cocci identification on Gram stain and rate of vancomycin discontinuation. Results: Of the 15 802 patient admissions in the SMART study, 6553 (41.5%) received empirical intravenous vancomycin. Respiratory sputum cultures demonstrated MRSA during 178 patient admissions. Among respiratory cultures that would ultimately grow MRSA, 85% were positive within 48 hours, and 97% were positive within 72 hours. Cultures demonstrated MRSA bacteremia during 85 patient admissions. In 83 cases (97.6%) of MRSA bacteremia, Gram-positive cocci were identified within 48 hours after the culture was obtained. Conclusion and Relevance: This analysis of a large cohort of critically ill adults receiving empirical vancomycin found that Staphylococcus aureus was present in all but 15% of cases of MRSA-positive respiratory cultures after 48 hours, whereas Gram-positive cocci were identified within 48 hours during nearly all episodes of MRSA bacteremia. These findings may inform the timing of discontinuation of empirical vancomycin among critically ill adults.

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Co-infection in critically ill patients with COVID-19: An observational cohort study from England

10.1101/2020.10.27.20219097 ◽

2020 ◽

Author(s):

Vadsala Baskaran ◽

Hannah Lawrence ◽

Louise Lansbury ◽

Karmel Webb ◽

Shahideh Safavi ◽

...

Keyword(s):

Cohort Study ◽

Critically Ill ◽

High Rate ◽

Gram Negative ◽

Icu Stay ◽

Observational Cohort ◽

Clinically Significant ◽

Critically Ill Adults ◽

Hospital Acquired ◽

Ill Adults

AbstractObjectiveTo describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England.MethodsA retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at <48 and >48 hours following hospital admission, corresponding to community and hospital-acquired co-infections.ResultsOf 254 patients studied (median age 59 years (IQR 49-69); 64.6% male), 139 clinically significant organisms were identified from 83(32.7%) patients. Bacterial co-infections were identified within 48 hours of admission in 14(5.5%) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli. The co-infection rate >48 hours after admission was 27/1000 person-days (95% CI 21.3-34.1). Patients with co-infections were more likely to die in ICU (crude OR 1.78,95% CI 1.03-3.08, p=0.04) compared to those without co-infections.ConclusionWe found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.

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