Diagnostic Microbiology and Infectious Disease 95 (2019) 185–190 Contents lists available at ScienceDirect Diagnostic Microbiology and Infectious Disease journal homepage: www.elsevier.com/locate/diagmicrobio Real-world use of telavancin in the treatment of osteomyelitis Louis D. Saravolatz a,⁎, Kerry O. Cleveland b, Khalid Rikabi c, Ali Hassoun d, Joseph Reilly e, Leonard B. Johnson a, Cedric Spak f, Sharon Valenti a, Susan Szpunar a a Ascension-St John Hospital and Wayne State University School of Medicine, Grosse Pointe Woods, Michigan, USA b University of Tennessee, Mephis Tennessee, USA c Geographic Medicine Services of Biloxi, Biloxi, Mississippi, USA d Alabama Infectious Diseases Center, Huntsville, Alabama, USA e AtlantiCare Regional Medical Center, Pomona, NJ, USA f North Texas Disease Consultants, Dallas, Texas, USA article info abstract Article history: This is a retrospective analysis of patients with osteomyelitis who received telavancin at some time during their Received 30 November 2018 treatment course. The primary outcome was the percent of patients cured or improved at the end of telavancin Received in revised form 17 May 2019 therapy (EOTT). The secondary outcome was the percent of patients cured or improved three months after dis- Accepted 18 May 2019 continuation of telavancin therapy. There were 32 cases of osteomyelitis with methicillin-resistant Staphylococ- Available online 28 May 2019 cus aureus identified in 17 (56.7%), methicillin-sensitive Staphylococcus aureus 2(6.6%), coagulase negative Keywords: staphylococci 6 (20.0%) and other pathogens, 5 (16.7%). At EOTT, 87.5% of patients had their osteomyelitis Telavancin cured and 94.6% had the infection cured at three months after telavancin was completed. The most common ad- Staphylococcus aureus verse events associated with telavancin were gastrointestinal in nature (nausea (25.8%), vomiting (9.7%) and di- Osteomyelitis arrhea (3.2%)) followed by metallic taste (6.5%). A favorable outcome was achieved for many patients receiving Methicillin-resistant the antimicrobial regimen that included telavancin for the treatment of osteomyelitis. Staphylococcus aureus © 2019 Elsevier Inc. All rights reserved. Osteomyelitis is one of the most challenging infections for the infec- identified pathogen. MRSA infections accounted for 10.08 discharges tious disease clinician to manage (Lew and Waldvogel, 2004). Treat- per million patients versus MSSA, which accounted for 7.27 discharges ment considerations involve antimicrobial selection, dosing, routes of per million patients for all S. aureus infection-related hospitalizations administration and surgical management. It has been well established in the year 2014. (Klein et al., 2017). In addition, the development of that late relapses may occur even after perceived successful antibiotic S. aureus strains with reduced susceptibility to vancomycin, therapy. This may occur in the range of 20–30% and does not appear vancomycin-intermediate and -resistant strains, and daptomycin non- to be related to a specific pathogen (Garcia del Pozo et al., 2018). In a se- susceptible strains pose additional challenges for the practicing clini- ries of 116 patients with osteomyelitis followed for more than 1 year cian. The prevalence of VISA was 7.93% between 2010 and 2014 after discharge, relapses occurred in 26 patients at a mean of 11.2 (Zhang et al., 2015) and the daptomycin non-susceptibility has been re- months (Garcia Del Pozo et al., 2018). In a recent publication of 1003 pa- ported occasionally from deep-seated infections but most recently in- tients with osteomyelitis treated in Europe S. aureus was the most com- creasing rates of daptomycin non-susceptible strains have been mon pathogen occurring 37.7% of cases (Li et al., 2019) In addition, the identified in either the skin or anterior nares of patients with atopic der- frequent occurrence of methicillin-resistant S. aureus (MRSA) as a path- matitis. The rate of non-susceptibility was 23.4% when identified by E ogen in osteomyelitis emphasizes the need for additional antimicrobial test (Blazewicz et al., 2017). agents with activity against this pathogen (Harting et al., 2017; Lamp Fortunately, VRSA strains are very uncommon, having been reported et al., 2007). Clinicians are challenged to find optimal treatment strate- in only 14 cases to date (McGuinness et al., 2017). The rationale for gies for S. aureus infections that will either enhance or serve as an alter- telavancin as an alternative treatment option is its excellent in vitro ac- native to available anti-staphylococcal therapies. tivity against MRSA and the emergence of less susceptible strains to With high rates of MRSA infections occurring in many regions, clini- available agents such as vancomycin and daptomycin (Karlowsky cians cannot rely on beta-lactams except for ceftaroline as initial empiric et al., 2015). In addition, telavancin has shown good antimicrobial activ- therapy for S. aureus infections or specific therapy when MRSA is the ity against staphylococcal biofilms and superior efficacy compared with vancomycin against MRSA strains causing biofilms. Telavancin also in- fi ’ ⁎ Corresponding author. Tel.: +1-313-343-3362; fax: +1-313-343-7784. hibits the formation of bio lms at concentrations below each isolate s E-mail address: [email protected] (L.D. Saravolatz). respective minimal inhibitory concentration (MIC) (Gander et al., https://doi.org/10.1016/j.diagmicrobio.2019.05.011 0732-8893/© 2019 Elsevier Inc. All rights reserved. 186 L.D. Saravolatz et al. / Diagnostic Microbiology and Infectious Disease 95 (2019) 185–190 2005). Thus, the identification of telavancin as a treatment option for se- carried out at the discretion of the infectious disease physician and rious infections such as osteomyelitis is important in expanding the cli- their medical team members. nicians’ choices in treatment. Institutional review board approval was obtained by the Ascension Telavancin, a semi-synthetic derivative of vancomycin, exhibits St John Hospital Institutional Review Board. Medical records were ab- concentration-dependent bactericidal activity via a dual mechanism of stracted using a standardized case report form (CRF). If data for the sec- action involving inhibition of bacterial cell wall synthesis as well as dis- ondary outcome (90-day outcomes) were not available, patients were ruption of cell membranes (Higgins et al., 2005)). It has broad anti- contacted by phone. All calls were made by the treating physician or re- staphylococcal activity, including activity against isolates with search staff and verbal consent was obtained at the start of the phone methicillin-resistance, and intermediate vancomycin susceptibility, call. (Karlowsky et al., 2015). Telavancin has been approved in the United States and Canada for the treatment of adult patients with complicated 1.5. Data collection skin and skin structure infections (cSSSI) due to susceptible Gram– positive organisms based on two identical double-blind, randomized, Data were collected on demographics, comorbidities, clinical and active-controlled multinational studies (ATLAS 1 and 2) (Stryjewski laboratory findings, radiologic findings, pathology, microbiology, site et al., 2008; Anon, 2014). Additionally, based on results from two iden- of infection, antibiotic use, adverse events, safety and outcomes. Stan- tical double-blind, randomized, active-controlled, multinational studies dardized case report forms were used to collect demographic and clini- (ATTAIN 1 and 2) (Rubinstein et al., 2011), telavancin received approval cal information on all patients treated with telavancin. The for the treatment of hospital -acquired and ventilator-associated bacte- osteomyelitis was categorized as acute if there were less than 30 days rial pneumonia due to susceptible isolates of S. aureus when alternative of signs and symptoms or chronic if it was longer. The site of infection agents are not appropriate (Anon, 2014). was defined by the investigators according to clinical signs and imaging There have been some published reports indicating clinical improve- results. Infections were classified as hematogenous and were noted if ment in patients with osteomyelitis treated with telavancin, Schroeder the patient had endocarditis or associated line infection or they were et al., 2018, Peyrani et al., 2012, Twilla et al., 2011, Xu et al., 2015). Our classified as contiguous in association with diabetic foot ulcer, surgical retrospective review was designed to capture clinical practice informa- wound infection, prosthetic joint infections or trauma. Patients’ associ- tion on the use of telavancin in the treatment of osteomyelitis. This ap- ated comorbidities such as diabetes mellitus, renal failure, prior ortho- proach is similar to what has been used in other published retrospective pedic surgery, and immunosuppression were recorded as documented case series and accepted for describing the experience with other anti- within the medical record. Adverse events, such as abnormal laboratory staphylococcal agents such as daptomycin use in the treatment of oste- testing, were reported as abnormal based on criteria used in clinical omyelitis (Rolston et al., 2007, Lamp et al., 2007). The primary objective practice at the respective institutions and was not protocol-driven. of this study was to retrospectively determine clinical outcomes of pa- tients treated with telavancin as part of their antimicrobial therapy in a post-marketing, real world evaluation. This paper describes