Modified reporting of positive urine cultures to reduce inappropriate antibiotic treatment of catheter-associated asymptomatic bacteriuria (CA-ASB) among inpatients, a randomized controlled trial

2021 ◽  
pp. 1-7
Author(s):  
Claire L. Pratt ◽  
Zahra Rehan ◽  
Lydia Xing ◽  
Laura Gilbert ◽  
Brenda Fillier ◽  
...  
Keyword(s):  
Adverse Events ◽  
Antibiotic Treatment ◽  
Controlled Trial ◽  
Tertiary Care ◽  
Asymptomatic Bacteriuria ◽  
Treatment Rate ◽  
Indwelling Catheters ◽  
Appropriate Treatment ◽  
Positive Urine ◽  
Standard Report

Abstract Objective: To determine whether modified reporting of positive urine cultures collected from indwelling catheters improved treatment decisions without causing harm. Design: Prospective, unblinded, randomized control trial. Setting: Two tertiary-care hospitals. Participants: Overall, 100 consecutive positive urine cultures collected from catheterized inpatients were randomized between standard and modified laboratory reporting between November 2018 and June 2019. Exclusion criteria were pregnancy, current antibiotic treatment, ICU or urology admission, or neutropenia. Intervention: The modified report included significant growth without providing identification, quantification, or susceptibility. The standard report included identification, quantitation and susceptibility. Diagnosis of catheter-associated asymptomatic bacteriuria (CA-ASB) and catheter-associated urinary tract infection (CA-UTI) followed published criteria, using prospective chart review. The appropriate antibiotic treatment was defined as treatment of CA-UTI, and no treatment of CA-ASB. Patients were followed for 7 days. Results: Of 543 urine cultures, 443 (82%) were excluded. Of 100 patients, 75 (75%) had CA-ASB and 25 (25%) had CA-UTI. Treatment was given to 45 of 75 CA-ASB patients (60%) and all 25 CA-UTI patients (100%). Appropriate treatment rate was higher in the modified reporting arm than in the standard reporting arm: 57% vs 50% (+7.4%; relative risk [RR], 1.15; P = .45). Untreated CA-ASB was higher in the modified reporting arm: 45% vs 33% (+12%; RR, 1.36; P = .30). The standard report was requested for 33% of modified reports. Furthermore, 4 deaths and 26.9% adverse events occurred in the modified reporting arm, and 3 deaths and 41.3% adverse events occurred in the standard reporting arm. Conclusions: Modified reporting increased the appropriateness of treatment, and may be safe. Clinical trials identifier: ClinicalTrials.gov#NCT03488355.

Modified Reporting of Positive Urine Cultures to Reduce Inappropriate Treatment of Asymptomatic Bacteriuria Among Nonpregnant, Noncatheterized Inpatients: A Randomized Controlled Trial

2018 ◽  
Vol 39 (07) ◽  
pp. 814-819 ◽  
Author(s):  
Peter Daley ◽  
David Garcia ◽  
Raheel Inayatullah ◽  
Carla Penney ◽  
Sarah Boyd
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Antibiotic Treatment ◽  
Controlled Trial ◽  
Asymptomatic Bacteriuria ◽  
Bacterial Count ◽  
Absolute Difference ◽  
Positive Urine ◽  
Standard Report

DESIGNWe conducted a randomized, parallel, unblinded, superiority trial of a laboratory reporting intervention designed to reduce antibiotic treatment of asymptomatic bacteriuria (ASB).METHODSResults of positive urine cultures from 110 consecutive inpatients at 2 urban acute-care hospitals were randomized to standard report (control) or modified report (intervention). The standard report included bacterial count, bacterial identification, and antibiotic susceptibility information including drug dosage and cost. The modified report stated: “This POSITIVE urine culture may represent asymptomatic bacteriuria or urinary tract infection. If urinary tract infection is suspected clinically, please call the microbiology laboratory … for identification and susceptibility results.” We used the following exclusion criteria: age <18 years, pregnancy, presence of an indwelling urinary catheter, samples from patients already on antibiotics, neutropenia, or admission to an intensive care unit. The primary efficacy outcome was the proportion of appropriate antibiotic therapy prescribed.RESULTSAccording to our intention-to-treat (ITT) analysis, the proportion of appropriate treatment (urinary tract infection treated plus ASB not treated) was higher in the modified arm than in the standard arm: 44 of 55 (80.0%) versus 29 of 55 (52.7%), respectively (absolute difference, −27.3%; RR, 0.42; P = .002; number needed to report for benefit, 3.7).CONCLUSIONSModified reporting resulted in a significant reduction in inappropriate antibiotic treatment without an increase in adverse events. Safety should be further assessed in a large effectiveness trial before implementationTRIAL REGISTRATION. clinicaltrials.gov#NCT02797613Infect Control Hosp Epidemiol 2018;814–819

Evaluating a Hospitalist-Based Intervention to Decrease Unnecessary Antimicrobial Use in Patients With Asymptomatic Bacteriuria

2016 ◽  
Vol 37 (9) ◽  
pp. 1044-1051 ◽  
Author(s):  
Sarah E. Hartley ◽  
Latoya Kuhn ◽  
Staci Valley ◽  
Laraine L. Washer ◽  
Tejal Gandhi ◽  
...  
Keyword(s):  
Educational Intervention ◽  
Tertiary Care ◽  
Asymptomatic Bacteriuria ◽  
Hospital Setting ◽  
Signs And Symptoms ◽  
Treatment Rate ◽  
Duration Of Treatment ◽  
Academic Center ◽  
Positive Urine ◽  
The Impact

OBJECTIVEInappropriate treatment of asymptomatic bacteriuria (ASB) in the hospital setting is common. We sought to evaluate the treatment rate of ASB at the 3 hospitals and assess the impact of a hospitalist-focused improvement intervention.DESIGNProspective, interventional trial.SETTINGTwo community hospitals and a tertiary-care academic center.PATIENTSAdult patients with a positive urine culture admitted to hospitalist services were included in this study. Exclusions included pregnancy, intensive care unit admission, history of a major urinary procedure, and actively being treated for a urinary tract infection (UTI) at the time of admission or >48 hours prior to urine collection.INTERVENTIONSAn educational intervention using a pocket card was implemented at all sites followed by a pharmacist-based intervention at the academic center. Medical records of the first 50 eligible patients at each site were reviewed at baseline and after each intervention for signs and symptoms of UTI, microbiological results, antimicrobials used, and duration of treatment for positive urine cultures. Diagnosis of ASB was determined through adjudication by 2 hospitalists and 2 infectious diseases physicians.RESULTSTreatment rates of ASB decreased (23.5%; P=.001) after the educational intervention. Reductions in treatment rates for ASB differed by site and were greatest in patients without classic signs and symptoms of UTI (34.1%; P<.001) or urinary catheters (31.2%; P<.001). The pharmacist-based intervention was most effective at reducing ASB treatment rates in catheterized patients.CONCLUSIONSA hospitalist-focused educational intervention significantly reduced ASB treatment rates. The impact varied across sites and by patient characteristics, suggesting that a tailored approach may be useful.Infect Control Hosp Epidemiol 2016;37:1044–1051

Antimicrobial use for asymptomatic bacteriuria—First, do no harm

2020 ◽  
Vol 42 (1) ◽  
pp. 37-42
Author(s):  
Yana Shpunt ◽  
Inna Estrin ◽  
Yossef Levi ◽  
Hodaya Saadon ◽  
Galit Ben-Yossef ◽  
...  
Keyword(s):  
Functional Status ◽  
Medical Center ◽  
Tertiary Care ◽  
Asymptomatic Bacteriuria ◽  
Antimicrobial Use ◽  
Renal Transplant Recipients ◽  
Common Error ◽  
Positive Urine ◽  
Male Sex ◽  
The Impact

AbstractObjective:Administration of antimicrobials to patients with asymptomatic bacteriuria (ASB) is a common error that can lead to worse outcomes. However, controlled analyses quantifying the commonality and impact of this practice are lacking. We analyzed the independent predictors for antimicrobials misuse in ASB and quantified the impact of this practice on clinical outcomes.Design:Retrospective case-control and cohort analyses for calendar year 2017.Setting:Tertiary-care, university-affiliated medical center.Patients:The study included adult (>18 years) patients with positive urine culture. Pregnant women, renal transplant recipients, and patients who underwent urologic procedures were excluded.Methods:ASB was determined according to US Centers for Disease Control and Prevention (CDC) criteria. Multivariable logistic regression models were constructed to analyze predictors and outcomes associated with antimicrobial use for patients with ASB.Results:The study included 1,530 patient-unique positive urine cultures. Among these patients, 610 patients (40%) were determined to have ASB. Of the 696 isolates, 219 (36%) were multidrug-resistant organisms (MDROs). Also, 178 (29%) patients received antimicrobials specifically due to the ASB. Independent predictors for improper administration of antimicrobials were dependent functional status (adjusted odds ratio [aOR], 2.3; 95% CI, 1.4–3.6) and male sex (aOR, 2; 95% CI, 1.25–2.6). Use of antimicrobials was independently associated with re-hospitalizations (aOR, 1.7; 95% CI, 1.1–2.6) and later, acute Clostridioides difficile infections (CDI) in the following 90 days (aOR, 4.5; 95% CI, 2–10.6).Conclusions:ASB is a common condition, frequently resulting from an MDRO. Male sex and poor functional status were independent predictors for mistreatment, and this practice was independently associated with rehospitalizations and CDI in the following 90 days.

scholarly journals Saccharomyces boulardii to Prevent Antibiotic-Associated Diarrhea: A Randomized, Double-Masked, Placebo-Controlled Trial

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Stephan Ehrhardt ◽  
Nan Guo ◽  
Rebecca Hinz ◽  
Stefanie Schoppen ◽  
Jürgen May ◽  
...  
Keyword(s):  
Placebo Group ◽  
Clostridium Difficile ◽  
Adverse Events ◽  
Antibiotic Treatment ◽  
Controlled Trial ◽  
Saccharomyces Boulardii ◽  
Serious Adverse Events ◽  
Antibiotic Associated Diarrhea ◽  
Clostridium Difficile Associated Diarrhea ◽  
Systemic Antibiotic Treatment

Abstract Background.  Antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) are common complications of antibiotic use. Data on the efficacy of probiotics to prevent AAD and CDAD are unclear. We aimed to evaluate the efficacy of Saccharomyces boulardii to prevent AAD and CDAD in hospitalized adult patients. Methods.  We conducted a multicenter, phase III, double-masked, randomized, placebo-controlled trial in hospitalized patients who received systemic antibiotic treatment in 15 hospitals in Germany between July 2010 and October 2012. Participants received Perenterol forte 250 mg capsules or matching placebo twice per day within 24 hours of initiating antibiotic treatment, continued treatment for 7 days after antibiotic discontinuation, and were then observed for 6 weeks. Results.  Two thousand four hundred forty-four patients were screened. The trial was stopped early for futility after inclusion of 477 participants. Two hundred forty-six patients aged 60.1 ± 16.5 years and 231 patients aged 56.5 ± 17.8 were randomized to the S boulardii group and the placebo group, respectively, with 21 and 19 AADs in the respective groups (P = .87). The hazard ratio of AAD in the S boulardii group compared with the placebo group was 1.02 (95% confidence interval, .55–1.90; P = .94). Clostridium difficile-associated diarrhea occurred in 0.8% of participants (4 of 477). Nine serious adverse events were recorded in the S boulardii group, and 3 serious adverse events were recorded in the placebo group. None were related to study participation. Conclusions.  We found no evidence for an effect of S boulardii in preventing AAD or CDAD in a population of hospitalized patients without particular risk factors apart from systemic antibiotic treatment. ClinicalTrials.gov Identifier.  NCT01143272.

scholarly journals CRP-guided antibiotic treatment in acute exacerbations of COPD in hospital admissions

2019 ◽  
Vol 53 (5) ◽  
pp. 1802014 ◽  
Author(s):  
H.J. Prins ◽  
Ruud Duijkers ◽  
Paul van der Valk ◽  
Marianne Schoorl ◽  
Johannes M.A. Daniels ◽  
...  
Keyword(s):  
Adverse Events ◽  
Antibiotic Treatment ◽  
Hospital Admissions ◽  
Day Treatment ◽  
Controlled Trial ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Serious Adverse Events ◽  
Patient Reported ◽  
Acute Exacerbations

The role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD) is controversial and a biomarker identifying patients who benefit from antibiotics is mandatory. We performed a randomised, controlled trial in patients with acute exacerbations of COPD, comparing C-reactive protein (CRP)-guided antibiotic treatment to patient reported symptoms in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy, in order to show a reduction in antibiotic prescription.Patients hospitalised with acute exacerbations of COPD were randomised to receive antibiotics based either on the GOLD strategy or according to the CRP strategy (CRP ≥50 mg·L−1).In total, 101 patients were randomised to the CRP group and 119 to the GOLD group. Fewer patients in the CRP group were treated with antibiotics compared to the GOLD group (31.7% versus 46.2%, p=0.028; adjusted odds ratio (OR) 0.178, 95% CI 0.077–0.411, p=0.029). The 30-day treatment failure rate was nearly equal (44.5% in the CRP group versus 45.5% in the GOLD-group, p=0.881; adjusted OR 1.146, 95% CI 0.649–1.187, p=0.630), as was the time to next exacerbation (32 days in the CRP group versus 28 days in the GOLD group, p=0.713; adjusted hazard ratio 0.878, 95% CI 0.649–1.187, p=0.398). Length of stay was similar in both groups (7 days in the CRP group versus 6 days in the GOLD group, p=0.206). On day-30, no difference in symptom score, quality of life or serious adverse events was detected.Use of CRP as a biomarker to guide antibiotic treatment in severe acute exacerbations of COPD leads to a significant reduction in antibiotic treatment. In the present study, no differences in adverse events between both groups were found. Further research is needed for the generalisability of these findings.

Safety, effectiveness and sustainability of a laboratory intervention to de-adopt culture of midstream urine samples among hospitalized patients

2020 ◽  
Vol 42 (1) ◽  
pp. 43-50
Author(s):  
Mohammad Mozafarihashjin ◽  
Jerome A. Leis ◽  
Lorraine Maze dit Mieusement ◽  
Liz McCreight ◽  
Susan Poutanen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Tertiary Care ◽  
Asymptomatic Bacteriuria ◽  
Urinary Symptoms ◽  
Care Hospital ◽  
Serious Adverse Events ◽  
Observational Cohort ◽  
Inpatient Units ◽  
Antibiotic Courses

AbstractObjective:To assess the safety, sustainability, and effectiveness of a laboratory intervention to reduce processing of midstream urine (MSU) cultures.Design:Prospective observational cohort.Setting:Medical and surgical inpatients in a tertiary-care hospital.Participants:The study included 1,678 adult inpatients with an order for MSU culture.Methods:From 2013 to 2019, ordered MSU cultures were not processed unless the laboratory was called. Patients were interviewed on days 0 and 4; from 2017 to 2019, day-30 follow-up was added. Primary outcome was serious adverse events due to not processing MSU cultures. Secondary outcomes were nonserious adverse events due to not processing MSU cultures, rates of MSU cultures submitted, proportion of MSU cultures processed, proportion of patients prescribed urinary tract infection (UTI)–directed antibiotics, and laboratory workload.Results:Among 912 and 459 patients followed to days 4 and 30, respectively, no serious adverse events attributable to not processing MSU cultures were identified. However, 6 patients (0.66%) had prolonged urinary symptoms potentially associated with not processing MSU cultures. We estimated that 4 patients missed having empiric antibiotics stopped in response to negative MSU cultures, and 99 antibiotic courses for asymptomatic bacteriuria (ASB) and 8 antibiotic-associated adverse events were avoided. The rate of submitted MSU samples and proportion of patients receiving empiric UTI-directed antibiotics did not change. The proportion of MSU cultures processed declined from 59% to 49% (P < .0001), and total laboratory workload was reduced by 185 hours.Conclusions:De-adopting the processing of MSU cultures from medical and surgical inpatient units is safe and sustainable, and it reduces antibiotic prescriptions for ASB at a cost of prolonged urinary symptoms in a small proportion of patients.

scholarly journals Are Urinalyses Used Inappropriately in the Diagnosis of Urinary Tract Infections?

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S350-S350 ◽  
Author(s):  
Ghada Elshimy ◽  
Vincent Mariano ◽  
Christina Mariyam Joy ◽  
Parminder Kaur ◽  
Monisha Singhal
Keyword(s):  
Urinary Tract ◽  
Antibiotic Treatment ◽  
Urinary Tract Infections ◽  
Urine Culture ◽  
White Blood Cells ◽  
Asymptomatic Bacteriuria ◽  
Further Education ◽  
Positive Urine ◽  
Tract Infections ◽  
Hospital Wards

Abstract Background One of the most readily available and cost effective tests in the diagnosis of urinary tract infections (UTI) is the urinalysis. Problems arise when antibiotic treatment is initiated in a patient who does not display typical signs and symptoms of UTI and for whom a urinalysis was obtained for other reasons. Methods This was a retrospective observational study carried out on 1000 patients with positive urine nitrite. Medical records were identified with subsequent analysis of urine culture and symptomatology. Recorded and analyzed data included: age, sex, location (emergency room (ER) or hospital ward), findings on urinalysis (pH, presence of leukocyte esterase(LE), epithelial cells, bacteria, and white blood cells (WBCs)) and antibiotic treatment. Results Of these 1000 patients with positive nitrite, we excluded 815 patients (81 had missing data, 466 met exclusion criteria and 268 had symptomatic UTI). 185 were found to not have any symptoms of a UTI. Inappropriate antibiotic treatment occurred in 108/185 patients (58.4%) and was significantly associated with greater amounts of bacteria and WBCs in the urinalyses (P = 0.008 and P = 0.029, respectively). It was also significantly more likely to occur in the ER than the hospital wards (92/147 treated in the ER vs. 16/37 treated on the hospital wards, P = 0.033). There was no significant association between antibiotic treatment and age, sex, urine pH, urine LE, and urine epithelial cell amounts (P &gt; 0.05). Urine cultures were not obtained in 69.7% of patients. A positive urine culture was significantly associated with inappropriate antibiotic treatment (P = 0.0006). The two most common presenting complaints were psychiatric complaints (21.6%) and vaginal bleeding (14.6%). Conclusion Urinalysis can be an invaluable diagnostic tool, but must be used and interpreted appropriately. There is a misperception that pyuria with bacteriuria defines UTI. However, positive results on a urinalysis alone in an asymptomatic patient is not enough to diagnose a UTI, and antibiotic treatment is only indicated in specific circumstances as outlined by IDSA guidelines for the treatment of asymptomatic bacteriuria. Further education targeting appropriate interpretation of urinalyses and IDSA guidelines is needed to decrease the unnecessary use of antibiotics. Disclosures All authors: No reported disclosures.

scholarly journals Análise da Revisão Cochrane: Antibióticos Destinados ao Tratamento da Bacteriúria Assintomática. Cochrane Database Syst Rev. 2015;4:CD009534.

2018 ◽  
Vol 31 (2) ◽  
pp. 76
Author(s):  
Miguel Bigotte Vieira ◽  
Mariana Alves ◽  
João Costa ◽  
António Vaz-Carneiro
Keyword(s):  
Systematic Review ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Adverse Events ◽  
Kidney Function ◽  
Antibiotic Treatment ◽  
Asymptomatic Bacteriuria ◽  
Controlled Trials ◽  
Symptomatic Urinary Tract Infection

Asymptomatic bacteriuria is frequently detected in women aged up to 60 years, patients with diabetes and elderly patients. The benefit of antibiotic treatment for this condition is controversial. The objective of this Cochrane systematic review was to assess the effectiveness and safety of antibiotic treatment for asymptomatic bacteriuria in adults. A systematic review of the literature up to 24 February 2015 was performed using the Cochrane Renal Group’s Specialised Register. Randomised controlled trials (RCTs) and quasirandomised controlled trials comparing antibiotics to placebo or no treatment for asymptomatic bacteriuria in adults were included. The outcomes of interest were the development of symptomatic urinary tract infection, complications, death, adverse events, development of antibiotic resistance, bacteriological cure, and decline in kidney function. Nine studies (1614 participants) were included in this review. The incidence of symptomatic urinary tract infection, complications or death was similar between groups. Antibiotic use was significantly associated with bacteriological cure and an increase in minor adverse events. No decline in kidney function was observed with any one of the treatments. According to the results of the studies included in this revision, authors have concluded that there is no clinical benefit in treating asymptomatic bacteriuria in adults.

scholarly journals 172. Evaluation of Multifaceted Antimicrobial Stewardship Interventions on The Treatment of Asymptomatic Bacteriuria

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S93-S94
Author(s):  
Tho H Pham ◽  
Angela Huang ◽  
Vanthida Huang ◽  
Scott T Hall
Keyword(s):  
Clostridium Difficile ◽  
Length Of Stay ◽  
Antibiotic Treatment ◽  
Clostridium Difficile Infection ◽  
Antimicrobial Stewardship ◽  
Antimicrobial Therapy ◽  
Asymptomatic Bacteriuria ◽  
Audit And Feedback ◽  
Hospital Length Of Stay ◽  
Positive Urine

Abstract Background Treatment of asymptomatic bacteriuria (ASB) and asymptomatic candiduria (ASC) is a leading cause of inappropriate use of antimicrobial therapy in many healthcare facility, and has been associated with undesirable outcomes such as Clostridium difficile infection, longer length of stay, long-term antibiotic resistance, and delayed time back to baseline activity. This evaluation was designed to utilize a pharmacy-driven multifaceted antimicrobial stewardship intervention to reduce the number of antibiotic treatment days in patients with ASB/ASC Methods This retrospective single-center study included hospitalized adult patients with a positive urinalysis and/or a positive urine culture with or without antimicrobial therapy from January-March 2019, compared to patients from January-March 2020 after initiation of a multifaceted antimicrobial stewardship intervention, including daily prospective audit and feedback. The primary outcome was the number of antibiotic treatment days in patients with ASB/ASC before and after implementation of the targeted antimicrobial stewardship interventions Results 189 patients were identified upon retrospective chart review in the pre-group and 110 patients were included in the post-group. Baseline characteristics were well-matched between groups, except that the pre-group had a higher percentage of patients coming from nursing facilities while the post-group had a significantly higher percentage of patients with positive urine cultures. Antibiotic treatment days were significantly lower in the post- versus pre-group 0 (IQR 0–3) vs. 3 (IQR 1–7), p&lt; 0.001. Incidence of ASB/ASC treatment was also significantly lower in the post- versus pre-group 45.5 vs 72.5%, p&lt; 0.001. There was no statistical difference between the two groups in 30-day mortality, 30-day hospital readmission, and hospital length of stay. There was one case of Clostridium difficile infection among patients being inappropriately managed with antibiotics in each groups Conclusion A multifaceted antimicrobial stewardship interventions successfully reduced antimicrobial treatment days in patients with ASB/ASC, as well as overall incidence of inappropriate treatment of ASB/ASC without increasing mortality or readmission rate Disclosures All Authors: No reported disclosures

scholarly journals EARLY LENZILUMAB TREATMENT OF COVID-19 PATIENTS USING C-REACTIVE PROTEIN AS A BIOMARKER IMPROVES EFFICACY: RESULTS FROM THE PHASE 3 LIVE-AIR TRIAL

2022 ◽  
Author(s):  
Zelalem Temesgen ◽  
Colleen F. Kelley ◽  
Frank Cerasoli ◽  
Adrian Kilcoyne ◽  
Dale Chappell ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Adverse Events ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Tertiary Care ◽  
Baseline Risk ◽  
C Reactive Protein ◽  
Phase 3 ◽  
Gm Csf ◽  
Reactive Protein

Objective: The LIVE-AIR trial demonstrated that the anti-GM-CSF monoclonal antibody, lenzilumab improved the likelihood of survival without invasive mechanical ventilation (SWOV) in COVID-19 patients; with greatest effect in those with baseline CRP below the median baseline value of 79 mg/L. Similar to GM-CSF, C-reactive protein (CRP) levels are correlated with COVID-19 severity. This current analysis assessed the utility of baseline CRP levels to guide treatment with lenzilumab. Design: LIVE-AIR was a phase 3, double-blind, placebo-controlled trial. Participants were randomized 1:1 and stratified according to age and disease severity, to receive lenzilumab or placebo on Day 0, were followed through Day 28. Setting: Secondary and tertiary care hospitals in the US and Brazil. Participants: 520 hospitalized COVID-19 participants with SpO2≤94% on room air or required supplemental oxygen but not invasive mechanical ventilation were included. Interventions: Lenzilumab (1800mg; divided as 3 doses, q8h) or placebo infusion alongside standard treatments including corticosteroids and remdesivir. Main outcome measures: A multi-variate logistic regression analysis assessed key baseline risk factors for progression to IMV or death. The primary endpoint, SWOV, and key secondary endpoints were analyzed according to baseline CRP levels in all participants with CRP values. Results: The multi-variate analysis demonstrated that elevated baseline plasma CRP was the most predictive feature for progression to IMV or death. SWOV was achieved in 152 (90%; 95%CI: 85to 94) lenzilumab and 183 (79%; 72 to 84) placebo participants with baseline CRP<150 mg/L and its likelihood was greater with lenzilumab than placebo (HR: 2.54; 95%CI, 1.46 to 4.41; p=0.0009) but not in participants with CRP≥150 mg/L at baseline. CRP as a covariate in the overall analysis demonstrated a statistically significant interaction with lenzilumab treatment (p=0.044). Grade ≥ 3 adverse events in participants with baseline CRP<150 mg/L were reported in 18% and 28% in lenzilumab or placebo, respectively. No treatment-emergent serious adverse events were attributable to lenzilumab. Conclusion: These finding suggest that COVID-19 participants with low baseline CRP levels achieve the greatest clinical benefit from lenzilumab and that baseline CRP levels may be a useful biomarker to guide therapeutic intervention. Trial Registration: ClinicalTrials.gov NCT04351152

Sign in / Sign up

Export Citation Format

Share Document