New Antibiotic Treatment for Patients With Serious Skin Infections Becomes Available in Wales

LONDON, August 1, 2013 /PRNewswire/ --

For UK medical media and Welsh regional reporters only

The All Wales Medicines Strategy Group (AWMSG) has recommended Zinforo^®▼ (ceftaroline fosamil), a new intravenous cephalosporin antibiotic,for use within NHS Wales for the treatment of complicated skin and soft tissue infections (cSSTIs).^[1] Ceftaroline fosamil represents an important new treatment option for patients and physicians, in an environment where relatively few new antibiotic agents are becoming available and where resistant and difficult to treat organisms often present treatment challenges.

The AWMSG has recommended ceftaroline fosamil as an option for restricted use in Wales for patients with cSSTIs, suspected to be due to Methicillin-resistant Staphylococcus aureus (MRSA).^[1] The AWMSG positive decision follows a similar positive recommendation by the Scottish Medicines Consortium (SMC) on 14 January 2013.^[2]

"Complicated skin infections are a common problem in hospitalised patients in Wales that have become increasingly difficult to treat, in part because of resistant infections such as MRSA," said Dr Neil Carbarns, Consultant Microbiologist at Aneurin Bevan Health Board. "Ceftaroline fosamil provides an important new treatment option that may help overcome some of the current challenges we face when managing cSSTI patients with MRSA infections, who require an effective treatment without compromising on tolerability."

Resistance to existing antibiotics is an increasing problem that can result in difficulty in treating infections, leading to failed therapy and potential complications.^[3] Antibiotic resistance remains a major public health issue in Wales, where it has been on the rise for the past 7 years.^[3] In November last year, Wales Chief Medical Officer (CMO) Dr Ruth Hussey wrote to prescribers expressing her concern over increasing antibiotic resistance.^[4] This has been echoed by England CMO, Dame Sally Davies, in her report published in March 2013, where she highlighted the impending public health threat posed by antibiotic resistance and called for action to be taken to address this.^[5]

Following authorisation from the European Medicines Agency (EMA) in September 2012, ceftaroline fosamil is now the only approved cephalosporin monotherapy in Europe with demonstrated clinical efficacy against MRSA. Across Europe, MRSA is a major cause of cSSTI, affecting 150,000 patients per year and resulting in extra in-hospital costs of €380 million.^[6] Recent data from Wales shows the rate of MRSA cases being 5 per 100,000 bed days.^[7]

The AWMSG recommendation is based on a clinical and cost effectiveness assessment of ceftaroline fosamil. In the Phase III clinical studies (CANVAS 1 and 2), ceftaroline fosamil demonstrated clinical efficacy in the treatment of cSSTI with the recognised tolerability profile of the cephalosporin class.^[8],[9] The most common adverse reactions occurring in ≥ 3% of patients treated with ceftaroline fosamil were diarrhoea, headache, nausea, and pruritus and were generally mild or moderate in severity.^[10]

"This positive recommendation is an important step towards making new treatment options available to patients and prescribers in the fight against serious bacterial infections," said Dr Sam Shaw, Head of Oncology and Infection at AstraZeneca UK. "We believe that maintaining and increasing a diverse armoury of antibiotics for use by infectious specialists is vital to combating future antimicrobial resistance, and we are therefore delighted that the AWMSG has recognized the importance of making ceftaroline fosamil available to patients in Wales."

AstraZeneca continues to invest significantly in the research and development of novel antibiotics.

NOTES TO EDITORS

The full guidance from the All Wales Medicines Strategy Group is detailed below:

Ceftaroline fosamil (Zinforo^®▼) is recommended as an option for restricted use within NHS Wales. Ceftaroline fosamil (Zinforo^®▼) should be restricted to use for the treatment of complicated skin and soft tissue infections in patients where methicillin-resistant S. aureus (MRSA) is suspected, only in the following settings:

• For infections caused by Gram-positive pathogens, only if intravenous (IV) vancomycin or IV teicoplanin is inappropriate, has not been tolerated or treatment modification is required; and IV daptomycin or IV linezolid is normally used.
• For mixed infections caused by common Gram-positive and Gram-negative pathogens (excluding extended-spectrum beta-lactamase-producing organisms, AmpC-producing organisms and non-fermenter Gram-negative organisms, such as Pseudomonas aeruginosa), only if IV vancomycin in combination with IV co-amoxiclav or IV teicoplanin in combination with IV co-amoxiclav is inappropriate, has not been tolerated or treatment modification is required; and IV daptomycin in combination with IV co-amoxiclav or IV linezolid in combination with IV co-amoxiclav is normally used.

Ceftaroline fosamil (Zinforo^®▼) is not recommended for use within NHS Wales for the treatment of complicated skin and soft tissue infections outside of these settings. Ceftaroline fosamil (Zinforo^®▼) is not recommended for use within NHS Wales for the treatment of community-acquired pneumonia.

About Zinforo^®▼(ceftaroline fosamil)

Ceftaroline fosamil is indicated in adults for the treatment of the following infections:^[10]

• Complicated skin and soft-tissue infections (cSSTI);
• Community-acquired pneumonia (CAP).*

*There is no experience with ceftaroline fosamil in the treatment of CAP due to MRSA. Caution is advised when treating such patients.

Ceftaroline fosamil will be available at the list price of £375 for a pack of 10 vials.

Ceftaroline fosamil is bactericidal and binds to and inhibits penicillin-binding proteins (PBPs), which are involved in bacterial cell wall synthesis and repair. The inhibition of PBPs leads to reduced bacterial cell replication and /or cell death. Ceftaroline fosamil was designed specifically to have a high affinity for specific PBPs in resistant isolates (PBP2X/2A/2B in Steptococcus pneumoniae and PBP2a in MRSA), which explains why it has additional activity compared to other cephalosporins.^[11]

About cSSTIs

Complicated Skin and Soft tissue Infections (cSSTI) are difficult-to-treat infections of the skin and underlying soft tissues such as fascia and muscle layers e.g. deep soft tissue abscesses, cellulitis and surgical site infections.^[12],[13] cSSTIs are among the most common antibiotic treated infections in the hospital setting and represent approximately 12% of all antibiotic-treated hospital patients in Europe.^[13]

cSSTIs are commonly associated with considerable morbidity, mortality, resource use and healthcare costs^[12],[14] and despite the availability of a variety of antibiotics to treat these infections, studies show that many patients do not receive effective first-line empiric treatment.^{[15],[16],[17]}

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.  For more information please visit: http://www.astrazeneca.com.

References

1. All Wales Medicines Strategy Group (AWMSG). http://www.awmsg.org/. Accessed July 2013
2. Scottish Medicines Consortuim. ceftaroline fosamil (Zinforo). http://www.scottishmedicines.org.uk/SMC_Advice/Advice/830_12_ceftaroline_fosamil_Zinforo/ceftaroline_fosamil_Zinforo. Accessed July 2013
3. Public Health Wales, Antimicrobial Resistance Programme Surveillance Unit: Antibacterial Resistance and Usage In Wales 2005-2011. November 2012.
4. Health in Wales. Get well soon - without antibiotics. November 2012. http://www.wales.nhs.uk/news/24907. Accessed July 2013
5. Davies, S.C. "Annual Report of the Chief Medical Officer, Volume Two, 2011, Infections and the rise of antimicrobial resistance" London: Department of Health (2013). Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/138331/CMO_Annual_Report_Volume_2_2011.pdf. Accessed July 2013
6. Kock R, Becker K. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Euro Surveill. 2010;15(41):pii=19688
7. Public Health Wales. Staphylococcus aureus Blood Stream Infection (Bacteraemia) Surveillance, October 2011-September 2012 http://www.wales.nhs.uk/sites3/page.cfm?orgId=379&pid=23910. Accessed July 2013
8. Corey GR, Wilcox M, Talbot GH, et al. Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection. Clin Infect Dis 2010;51:641-50.
9. File TM, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia. Clin Infect Dis 2010; 51:1395-405.
10. ZINFORO™ (ceftaroline fosamil) European Summary of Product Characteristics 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002252/WC500132586.pdf. Accessed July 2013
11. Kosowska-Shick K, McGhee, PL.  Affinity of ceftaroline and other β-lactams for Penicillin-Binding proteins from Staphylcoccus aureus and Streptococcus pneumoniae.  Antimicrob Agents Chemother. 2010;54:1670-7.
12. Raghavan M, Linden PK. Newer treatment options for skin and soft tissue infections. Drugs 2004;64:1621-42.
13. Decision Resources. Skin and skin structure infections (Europe). 2009
14. Cainzos M. Review of the guidelines for complicated skin and soft tissue infections and intra-abdominal infections--are they applicable today? Clin Microbiol Infect. 2008;14(Suppl 6):9-18.
15. Edelsberg J, Berger A, Weber DJ, Mallick R, Kuznik A, Oster G. Clinical and economic consequences of failure of initial antibiotic therapy for hospitalized patients with complicated skin and skin-structure infections. Infect Control Hosp Epidemiol 2008;29:160-9.
16. Zilberberg MD, Shorr AF, Micek ST, et al. Epidemiology and outcomes of hospitalizations with complicated skin and skin-structure infections: implications of healthcare-associated infection risk factors. Infect Control Hosp Epidemiol 2009;30:1203-10.
17. Eagye KJ, Kim A, Laohavaleeson S, Kuti JL, Nicolau DP. Surgical site infections: does inadequate antibiotic therapy affect patient outcomes? Surg Infect 2009;10:323-31.

ATLAS ID number: 45,905.011Jul 2013
Exp: 09/07/2014

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