Vancomycin De-escalation Therapy in Patients With Pneumonia

Pneumonia Clinical Trial

Official title:

Vancomycin De-escalation Therapy in Patients With Pneumonia and Negative MRSA Nasal Swab

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03586362
• Other study ID #: 17-406
• Status: Active, not recruiting
• Start date: February 8, 2018
• Est. completion date: December 30, 2023

Study information

• Verified date: July 2022
• Source: CAMC Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a non-inferiority study evaluating clinical improvement rate when using MRSA nasal swabs to guide discontinuation of vancomycin for empiric coverage for MRSA pneumonia.

Description:

Current clinical guidelines recommend including vancomycin in initial empiric therapy if risk factors for MRSA infection are present, or there is a high incidence of MRSA locally. Prolonged exposure to vancomycin, however, has been linked with the risk of vancomycin-associated kidney failure. Studies have reported that a MRSA nasal swab may be used to predict the presence of MRSA pneumonia. Specifically, pneumonia patients with negative MRSA nasal swabs are 95-99% likely to not have pneumonia due to MRSA. There is limited data, however, evaluating the use of a MRSA nasal swab to guide vancomycin therapy. Accordingly, in this study, pneumonia patients in the intervention arm will have empiric vancomycin discontinued following a negative MRSA nasal swab. In the control arm, patients vancomycin will not be discontinued based on the MRSA nasal swab result. The rate of clinical resolution will be compared between these two study arms.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 278
• Est. completion date: December 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years old

• Patients admitted to Charleston Area Medical Center (CAMC) through the Emergency Department who meet the CDC criteria for pneumonia.

• Nasal surveillance culture for MRSA obtained in the Emergency Department

• Patients receiving vancomycin and additional antibiotic therapy for gram-negative coverage

Exclusion Criteria:

• Persistent vasopressor requirements when MRSA nasal swab results are available

• Patients not meeting the CDC criteria for pneumonia

• Patients presenting to the ED with leukopenia (=4000) without previous documentation of normal or elevated WBC

• Patients receiving empiric MRSA antibiotic therapy other than vancomycin for pneumonia

• Patients with the diagnosis of lung abscess

• Patients not receiving vancomycin therapy before MRSA nasal swab results are reported

• Immunocompromised individuals. i.e. patients with AIDS/HIV, vasculitis on immune suppressor therapy, steroid therapy for more than one week prior admission or who received chemotherapy in the last 3 months

• Patients who do not have a MRSA nasal swab obtained in the ED

• Nares swab obtained after the completion of the first administered dose of an antibiotic with activity against MRSA

• Patients with MRSA bacteremia

• Patients with chronic tracheostomy

Related Conditions & MeSH terms

• Pneumonia

Locations

Country	Name	City	State
United States	Charleston Area Medical Center	Charleston	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
CAMC Health System

Country where clinical trial is conducted

United States, 

References & Publications (23)

Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004 Aug;8(4):R204-12. Epub 2004 May 24. Review. — View Citation

Cook DJ, Kollef MH. Risk factors for ICU-acquired pneumonia. JAMA. 1998 May 27;279(20):1605-6. — View Citation

Craven DE, Steger KA. Epidemiology of nosocomial pneumonia. New perspectives on an old disease. Chest. 1995 Aug;108(2 Suppl):1S-16S. Review. — View Citation

Edwards JR, Peterson KD, Andrus ML, Dudeck MA, Pollock DA, Horan TC; National Healthcare Safety Network Facilities. National Healthcare Safety Network (NHSN) Report, data summary for 2006 through 2007, issued November 2008. Am J Infect Control. 2008 Nov;36(9):609-26. doi: 10.1016/j.ajic.2008.08.001. Erratum in: Am J Infect Control. 2009 Jun;37(5):425. Am J Infect Control. 2009 Jun;37(5):425. — View Citation

Erb CT, Patel B, Orr JE, Bice T, Richards JB, Metersky ML, Wilson KC, Thomson CC. Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia. Ann Am Thorac Soc. 2016 Dec;13(12):2258-2260. — View Citation

Greenaway CA, Embil J, Orr PH, McLeod J, Dyck B, Nicolle LE. Nosocomial pneumonia on general medical and surgical wards in a tertiary-care hospital. Infect Control Hosp Epidemiol. 1997 Nov;18(11):749-56. — View Citation

Harigaya Y, Bulitta JB, Forrest A, Sakoulas G, Lesse AJ, Mylotte JM, Tsuji BT. Pharmacodynamics of vancomycin at simulated epithelial lining fluid concentrations against methicillin-resistant Staphylococcus aureus (MRSA): implications for dosing in MRSA pneumonia. Antimicrob Agents Chemother. 2009 Sep;53(9):3894-901. doi: 10.1128/AAC.01585-08. Epub 2009 Jul 13. — View Citation

Hazlewood KA, Brouse SD, Pitcher WD, Hall RG. Vancomycin-associated nephrotoxicity: grave concern or death by character assassination? Am J Med. 2010 Feb;123(2):182.e1-7. doi: 10.1016/j.amjmed.2009.05.031. Review. — View Citation

Hiett J, Patel RK, Tate V, Smulian G, Kelly A. Using active methicillin-resistant Staphylococcus aureus surveillance nasal swabs to predict clinical respiratory culture results. Am J Health Syst Pharm. 2015 Jun 1;72(11 Suppl 1):S20-4. doi: 10.2146/ajhp140820. — View Citation

Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother. 1997 Jul;40(1):135-6. — View Citation

Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Feb 1;52(3):e18-55. doi: 10.1093/cid/ciq146. Epub 2011 Jan 4. Erratum in: Clin Infect Dis. 2011 Aug 1;53(3):319. — View Citation

Minejima E, Choi J, Beringer P, Lou M, Tse E, Wong-Beringer A. Applying new diagnostic criteria for acute kidney injury to facilitate early identification of nephrotoxicity in vancomycin-treated patients. Antimicrob Agents Chemother. 2011 Jul;55(7):3278-83. doi: 10.1128/AAC.00173-11. Epub 2011 May 16. — View Citation

Pitz AM, Yu F, Hermsen ED, Rupp ME, Fey PD, Olsen KM. Vancomycin susceptibility trends and prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus in clinical methicillin-resistant S. aureus isolates. J Clin Microbiol. 2011 Jan;49(1):269-74. doi: 10.1128/JCM.00914-10. Epub 2010 Oct 20. — View Citation

Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1121-9. — View Citation

Richter SS, Satola SW, Crispell EK, Heilmann KP, Dohrn CL, Riahi F, Costello AJ, Diekema DJ, Doern GV. Detection of Staphylococcus aureus isolates with heterogeneous intermediate-level resistance to vancomycin in the United States. J Clin Microbiol. 2011 Dec;49(12):4203-7. doi: 10.1128/JCM.01152-11. Epub 2011 Oct 5. — View Citation

Rubinstein E, Kollef MH, Nathwani D. Pneumonia caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S378-85. doi: 10.1086/533594. Review. — View Citation

Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98. doi: 10.2146/ajhp080434. Review. Erratum in: Am J Health Syst Pharm. 2009 May 15;66(10):887. — View Citation

Schurink CAM, Nieuwenhoven CAV, Jacobs JA, Rozenberg-Arska M, Joore HCA, Buskens E, Hoepelman AIM, Bonten MJM. Clinical pulmonary infection score for ventilator-associated pneumonia: accuracy and inter-observer variability. Intensive Care Med. 2004 Feb;30(2):217-224. doi: 10.1007/s00134-003-2018-2. Epub 2003 Oct 18. — View Citation

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. — View Citation

Stevens V, Yoo, M, Brown J. Cost and Length of Stay Associated with Vancomycin-Induced Nephrotoxicity. Value in Health , Volume 16 , Issue 7 , A349

Tilahun B, Faust AC, McCorstin P, Ortegon A. Nasal colonization and lower respiratory tract infections with methicillin-resistant Staphylococcus aureus. Am J Crit Care. 2015 Jan;24(1):8-12. doi: 10.4037/ajcc2015102. — View Citation

van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013 Feb;57(2):734-44. doi: 10.1128/AAC.01568-12. Epub 2012 Nov 19. Review. — View Citation

Zimlichman E, Henderson D, Tamir O, Franz C, Song P, Yamin CK, Keohane C, Denham CR, Bates DW. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med. 2013 Dec 9-23;173(22):2039-46. doi: 10.1001/jamainternmed.2013.9763. Review. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Clinical Improvement	Rate of clinical improvement following 7 days of antibiotic therapy for pneumonia. Clinical improvement rate is defined as the percentage of patients who had clinical documentation of improvement or resolution of all clinical signs and symptoms of pneumonia present at the time of pneumonia diagnosis.; Afebrile: Temperature <38.0ºC or <100.4ºF; Improvement of respiratory symptoms and signs per clinical documentation: cough, dyspnea, tachypnea, purulent sputum, increase respiratory secretions, increased suctioning requirements; White blood count (WBC) trending down by at least 25%, or when baseline was= 15,000 mm3, or return to the normal values; Less oxygen supplementation and ventilation; Chest radiographic improvement per radiologist report (e.g. infiltrate, consolidation or cavitation)	Evaluation will be completed 48 hours after 7 days of antibiotic therapy for pneumonia.
Secondary	Hospital Length of Stay	Date of admission to date of discharge from the hospital	During patient hospital stay for up to 6 months
Secondary	In-hospital mortality	Number of deaths	During patient hospital stay for up to 6 months
Secondary	Rate of vancomycin-associated kidney injury defined as a 50% increase in serum creatinine or at least two consecutive increases in serum creatinine by 0.5 mg/dL after at least 48 hours of vancomycin therapy.	Number of kidney injuries following administration of vancomycin	Time between vancomycin administration and discharge from hospital for up to 6 months.
Secondary	Hospital complications, such as MRSA bacteremia and septic shock	Number of MRSA bacteremia and septic shock patients whose MRSA nasal swab is negative and have MRSA pneumonia	During patient hospital stay for up tp 6 months
Secondary	Billing cost associated with vancomycin therapy and laboratory monitoring	Total charges associated with vancomycin therapy and laboratory monitoring	During patient hospital stay for up to 6 months

External Links

•   19. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, n.d. Web. 26 Jan. 2017
•   Hospital-Acquired,Health Care-Associated, andVentilator-Associated Pneumonia." Hospital-Acquired, Health Care-Associated, and Ventilator-Associated Pneumonia. N.p., n.d. Web. 19 Jan. 2017
•   New CDC study highlights burden of pneumonia hospitalizations among US adults." Centers for Disease Control and Prevention. Accessed January 18, 2017
•   Pneumonia." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 06 Oct. 2016. Web. 18 Jan. 2017