ReviewThe clinical positioning of telavancin in Europe
Introduction
On 18 March 2014, the lipoglycopeptide antimicrobial telavancin (VIBATIV®) became available once again in Europe. This followed the original 2011 approval of telavancin for proven or suspected meticillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia, including ventilator-associated pneumonia [1]. However – and uniquely in this field – the positive opinion of the European Medicines Agency (EMA) was qualified by the statement that telavancin should be used only in situations where it is known or suspected that other alternatives are not suitable. Given that clinical experience with telavancin in Europe is limited and that the compound comes into clinical use with this significant caveat about its utilisation, this review is intended to provide an overview of telavancin's clinical positioning in today's anti-MRSA hospital antimicrobial armamentarium.
Section snippets
History of telavancin in Europe
Telavancin was the first marketed lipoglycopeptide. It is a semisynthetic derivative of vancomycin with structural alterations instigating potent activity against multiple Gram-positive organisms. Discovered in 2004, telavancin was designed to share the favourable distribution properties of its parent compound while maintaining potent activity against antimicrobial-resistant organisms, as evaluated in animal models [2].
Telavancin was jointly developed by Theravance, Inc. (South San Francisco,
Licensing of telavancin
Telavancin was approved and launched in the USA in 2009 for the treatment of adult patients with complicated SSSIs caused by susceptible Gram-positive bacteria, including both MRSA and meticillin-susceptible S. aureus (MSSA) [18]. Although approved in Canada in 2009 for the same indication as in the USA (complicated SSSI), telavancin has not been launched in this country [19]. In June 2013, licensing of telavancin in the USA was expanded to include the treatment of adult patients with
Antimicrobial properties of telavancin
Telavancin displays activity against a broad spectrum of Gram-positive organisms, including those with reduced susceptibility to vancomycin [2], [3], [24], [25], [26], [27], [28], [29], [30]; however, as with other glycopeptides, it does not have activity against Gram-negative organisms. Telavancin has a dual mechanism of action, targeting the bacterial cell wall and membrane. As with vancomycin, and oritavancin and dalbavancin (the other semisynthetic lipoglycopeptides), telavancin inhibits
Clinical experience with telavancin in its licensed indications
The pooled findings from two phase 3 clinical studies of telavancin for the treatment of patients with hospital-acquired, Gram-positive pneumonia [the Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) studies; NCT00107952 and NCT00124020] have been described in detail previously [13]. Briefly, 1532 patients from 274 study sites in 38 countries were randomised and 1503 patients received at least one dose of telavancin (10 mg/kg q24h) or the comparator vancomycin [1 g
Metabolism
Telavancin is not extensively metabolised and has been shown to be metabolically stable. Its plasma protein binding is high at ca. 90%. This is primarily to serum albumin and is not affected by renal or hepatic impairment [23]. Telavancin is not a substrate for any of the seven recombinant human CYP450s examined (1A2, 2C9, 2C19, 2D6, 3A4, 3A5 and 4A11). In humans, telavancin is excreted largely unchanged in the urine [23], [60], [61]. Following intravenous administration of 14C-labelled
Clinical positioning of telavancin
Uniquely, telavancin has been introduced into the clinical arena with the specific intention that it will be used effectively only as a last resort and where renal function permits. Undoubtedly this will present challenges for clinicians since the frequency of its deployment will inevitably be low so that in many instances there will be no familiarity with, or recollection of, using the compound. In some last-resort situations, clinicians may well be faced with the conundrum of considering
Conclusions
MRSA remains a public health priority in Europe and, despite a decrease in the incidence of MRSA infections in recent years, the proportion of S. aureus isolates reported as MRSA in 2012 was ≥25% in 7 of 30 European countries that provided surveillance reports [70]. Treatment options for hospital-acquired and ventilator-associated pneumonia caused by MRSA are limited in Europe, with vancomycin and linezolid being the most widely used [66]. However, these treatments have limitations, including
Funding
None.
Competing interests
RM has provided consultancy services and/or has been a speaker for AstraZeneca, Astellas, Basilea, Bayer Healthcare, Clinigen Specialty Pharmaceuticals, Janssen, Johnson & Johnson, Novartis, Pfizer and Sumitomo; GC has provided consultancy services for Clinigen Specialty Pharmaceuticals; PC has provided consultancy services and/or has been a speaker for Novartis, Pfizer and Cubist; HML has provided consultancy services and/or has been a speaker for AstraZeneca, Astellas, Basilea, Bayer
Ethical approval
Not required.
Acknowledgments
Medical writing support was provided by Rhian Harper Owen, an independent medical writer, funded by Clinigen Specialty Pharmaceuticals, Burton-on-Trent, UK (the European distributors of telavancin). The concept for the paper was developed at an Advisory Board held and funded by Clinigen Specialty Pharmaceuticals and at which the authors participated. The authors received no payment in respect of this publication.
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2018, Clinics in Chest MedicineCitation Excerpt :Telavancin is currently approved by the European Medicines Agency for the treatment of adult patients with HAP (including VAP) only for MRSA known or suspected infections and when other alternative treatments are not suitable. Moreover, it is strongly suggested to restrict the use of telavancin only to patients with normal renal function.98 Delafloxacin belongs to the class of fluoroquinolones and exerts a potent anti-MRSA activity together with a broad-spectrum activity against both gram-positive (including penicillin-sensitive, penicillin-resistant, and levofloxacin-resistant S pneumoniae, Streptococcus pyogenes, and Enterococci) and gram-negative pathogens (E coli, Klebsiella spp, H influenzae, M catharralis, and quinolone-susceptible P aeruginosa).99–101
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2017, Journal of Global Antimicrobial ResistanceCitation Excerpt :In 2013, telavancin was approved by the FDA for the treatment of HAP and VAP caused by S. aureus in the absence of alternatives following an earlier approval for the treatment of cSSSI [63]. Its license in Europe is more restricted, being approved for nosocomial pneumonia that is known or suspected to be caused by MRSA in situations where alternative antibiotics cannot be used [64]. Although all of the lipoglycopeptides are presently licensed for narrow indications, in future their role could expand to include their use for the treatment of bacteraemia, infective endocarditis and osteomyelitis [65].
Outpatient treatment of osteomyelitis with telavancin
2017, International Journal of Antimicrobial AgentsCitation Excerpt :In addition, it is approved for hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP) caused by susceptible isolates of S. aureus when alternative treatments are not suitable [10]. Telavancin is approved in Europe for nosocomial pneumonia caused by MRSA and in Canada for the treatment of HABP/VABP and cSSSI caused by susceptible Gram-positive pathogens [11]. The drug became unavailable in the USA in December 2011 owing to the inability of the contract manufacturer to supply the drug, and it was re-introduced in August 2013.
Activity of telavancin against Gram-positive pathogens isolated from bone and joint infections in North American, Latin American, European and Asia-Pacific nations
2017, Diagnostic Microbiology and Infectious DiseaseCitation Excerpt :Telavancin, a once-daily dosed lipoglycopeptide, has been approved for use in the United States (US), Canada, and Europe (EU) for designated infections caused by Gram-positive organisms (Corey et al., 2014; Masterton et al., 2015; VIBATIV Package Insert, 2016).