Comparison of Sequential Dalbavancin With Standard-of-Care Treatment for Staphylococcus aureus Bloodstream Infections

Kyle C Molina, Cali Lunowa, Madelyn Lebin, Andrea Segerstrom Nunez, Sara F Azimi, Martin Krsak, Scott W Mueller, Matthew A Miller, Kyle C Molina, Cali Lunowa, Madelyn Lebin, Andrea Segerstrom Nunez, Sara F Azimi, Martin Krsak, Scott W Mueller, Matthew A Miller

Abstract

Background: Dalbavancin (DAL) is a long-acting lipoglycopeptide with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). This study investigates DAL as sequential therapy in S. aureus bloodstream infections (BSIs).

Methods: We conducted a retrospective cohort study from 2014 to 2021 comparing sequential DAL with standard-of-care therapy (SoC) for S. aureus BSI. The primary outcome was 90-day clinical failure (90-day all-cause mortality or 90-day recurrence). Secondary outcomes were incidence of acute kidney injury, creatinine phosphokinase elevations, catheter-related thrombosis, and hospital-acquired infections. Analyses were adjusted using inverse probability of treatment weighting (IPTW).

Results: Overall, 225 patients (45 DAL, 180 SoC) were included. DAL patients had a higher incidence of community-acquired infection and persons who use drugs; SoC patients had more comorbidities and a longer duration of bacteremia. MRSA incidence was similar between the DAL and SoC groups. The median length of stay was 16 days among DAL recipients compared with 24 days among SoC recipients. Central catheter placement was 17.8% compared with 57.2% in the SoC group. Ninety-day clinical failure occurred in 13.3% and 18.3% of participants in the DAL and SOC groups, respectively. In IPTW-adjusted analysis, sequential DAL was not associated with 90-day clinical failure (adjusted odds ratio, 0.94; 95% CI, 0.333-2.32).

Conclusions: This study provides preliminary evidence that select patients with S. aureus BSI treated with sequential DAL have similar clinical failure rates, with significant reductions in catheter placement and hospital length of stay compared with SoC. Further prospective evaluation is needed.

Keywords: BSI; MRSA; SAB; long-acting lipoglycopeptides.

© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Patient selection diagram. Abbreviations: CNS, central nervous system; DAL, dalbavancin; IV, intravenous; SoC, standard of care.

References

    1. Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus Infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015; 28:603–61. doi:10.1128/CMR.00134-14.
    1. Thampi N, Showler A, Burry L, et al. . Multicenter study of health care cost of patients admitted to hospital with Staphylococcus aureus bacteremia: impact of length of stay and intensity of care. Am J Infect Control 2015; 43:739–44. doi:10.1016/j.ajic.2015.01.031.
    1. Liu C, Bayer A, Cosgrove SE, et al. . 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; 52:e18–55. doi:10.1093/cid/ciq146.
    1. Baddour LM, Wilson WR, Bayer AS, et al. . Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation 2015; 132:1435–86. doi:10.1161/CIR.0000000000000296.
    1. Holland TL, Arnold C, Fowler VG. Clinical management of Staphylococcus aureus bacteremia. JAMA 2014; 312:1330–41. doi:10.1001/jama.2014.9743.
    1. Willekens R, Puig-Asensio M, Ruiz-Camps I, et al. . Early oral switch to linezolid for low-risk patients with Staphylococcus aureus bloodstream infections: a propensity-matched cohort study. Clin Infect Dis 2019; 69:381–7. doi:10.1093/cid/ciy916.
    1. Jorgensen SCJ, Lagnf AM, Bhatia S, Shamim MD, Rybak MJ. Sequential intravenous-to-oral outpatient antibiotic therapy for MRSA bacteraemia: one step closer. J Antimicrob Chemother 2019; 74:489–98. doi:10.1093/jac/dky452.
    1. Bupha-Intr O, Blackmore T, Bloomfield M. Efficacy of early oral switch with β-lactams for low-risk Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 2020; 64:e02345–19. doi:10.1128/AAC.02345-19.
    1. Townsend J, Keller S, Tibuakuu M, et al. . Outpatient parenteral therapy for complicated Staphylococcus aureus infections: a snapshot of processes and outcomes in the real world. Open Forum Infect Dis 2018; 5:XXX–XX. doi:10.1093/ofid/ofy274.
    1. Buehrle DJ, Shields RK, Shah N, Shoff C, Sheridan K. Risk factors associated with outpatient parenteral antibiotic therapy program failure among intravenous drug users. Open Forum Infect Dis 2017; 4:XXX–XX. doi:10.1093/ofid/ofx102.
    1. Bryson-Cahn C, Beieler AM, Chan JD, Harrington RD, Dhanireddy S. Dalbavancin as secondary therapy for serious Staphylococcus aureus infections in a vulnerable patient population. Open Forum Infect Dis 2019; 6:XXX–XX. doi:10.1093/ofid/ofz028.
    1. Pfaller MA, Mendes RE, Duncan LR, Flamm RK, Sader HS. Activity of dalbavancin and comparator agents against gram-positive cocci from clinical infections in the USA and Europe 2015–16. J Antimicrob Chemother 2018; 73:2748–56. doi:10.1093/jac/dky235.
    1. Molina KC, Miller MA, Mueller SW, Van Matre ET, Krsak M, Kiser TH. Clinical pharmacokinetics and pharmacodynamics of dalbavancin. Clin Pharmacokinet 2022; 61:363–74. doi:10.1007/s40262-021-01088-w.
    1. Dunne MW, Puttagunta S, Sprenger CR, Rubino C, Van Wart S, Baldassarre J. Extended-duration dosing and distribution of dalbavancin into bone and articular tissue. Antimicrob Agents Chemother 2015; 59:1849–55. doi:10.1128/AAC.04550-14.
    1. Morrisette T, Miller MA, Montague BT, Barber GR, McQueen RB, Krsak M. On- and off-label utilization of dalbavancin and oritavancin for gram-positive infections. J Antimicrob Chemother 2019; 74:2405–16. doi:10.1093/jac/dkz162.
    1. Hidalgo-Tenorio C, Vinuesa D, Plata A, et al. . DALBACEN cohort: dalbavancin as consolidation therapy in patients with endocarditis and/or bloodstream infection produced by gram-positive cocci. Ann Clin Microbiol Antimicrob 2019; 18:30. doi:10.1186/s12941-019-0329-6
    1. Rappo U, Puttagunta S, Shevchenko V, et al. . Dalbavancin for the treatment of osteomyelitis in adult patients: a randomized clinical trial of efficacy and safety. Open Forum Infect Dis 2018; 6:XXX–XX. doi:10.1093/ofid/ofy331.
    1. Thomas G, Henao-Martínez AF, Franco-Paredes C, Chastain DB. Treatment of osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections with dalbavancin and oritavancin: a systematic review. Int J Antimicrob Agents 2020; 56:106069. doi:10.1016/j.ijantimicag.2020.106069.
    1. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36:309–32. doi:10.1016/j.ajic.2008.03.002.
    1. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42:377–81. doi:10.1016/j.jbi.2008.08.010
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13:818–29. doi:10.1097/00003246-198510000-00009.
    1. Quan H, Sundararajan V, Halfon P, et al. . Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005; 43:1130–9. doi:10.1097/01.mlr.0000182534.19832.83.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) . Acute kidney injury work group KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2:1–138. doi:10.1038/kisup.2012.1
    1. Jorgensen SCJ, Zasowski EJ, Trinh TD, et al. . Daptomycin plus β-lactam combination therapy for methicillin-resistant Staphylococcus aureus bloodstream infections: a retrospective, comparative cohort study. Clin Infect Dis 2020; 71:1–10. doi: 10.1093/cid/ciz746.
    1. Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials – a practical guide with flowcharts. BMC Med Res Methodol 2017; 17:162. doi:10.1186/s12874-017-0442-1.
    1. Tobudic S, Forstner C, Burgmann H, et al. . Dalbavancin as primary and sequential treatment for gram-positive infective endocarditis: 2-year experience at the general hospital of Vienna. Clin Infect Dis 2018; 67:795–8. doi:10.1093/cid/ciy279.
    1. Veve MP, Patel N, Smith ZA, Yeager SD, Wright LR, Shorman MA. Comparison of dalbavancin to standard-of-care for outpatient treatment of invasive gram-positive infections. Int J Antimicrob Agents 2020; 56:106210. doi:10.1016/j.ijantimicag.2020.106210.
    1. Dagher M, Fowler VG Jr, Wright PW, Staub MB. A narrative review of early oral stepdown therapy for the treatment of uncomplicated Staphylococcus aureus bacteremia: yay or nay? Open Forum Infect Dis 2020; 7:XXX–XX. doi:10.1093/ofid/ofaa151.
    1. Werth BJ, Jain R, Hahn A, et al. . Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen. Clin Microbiol Infect 2018; 24:429.e1–5. doi:10.1016/j.cmi.2017.07.028.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe