New European Real World Data Show High Requirement for Treatment Modification and Use of Hospital Resources Associated with First-Line Antibiotic Use for Serious Skin Infections and Pneumonia

LONDON, March 31, 2012 /PRNewswire/ --

Findings of the new REACH study (a REtrospective study to Assess the Clinical Management of Patients With Moderate-to-severe cSSTI or CAP Infections in the Hospital Setting) announced today at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), revealed that between 37 and 47 per cent of patients hospitalised with complicated skin and soft tissue infections (cSSTIs) or community acquired pneumonia (CAP) throughout Europe required modification of their initial, first-line antibiotic treatment. [1,2] This need for first-line treatment modification was associated with an increased use of hospital resources, which is an ever-growing challenge for hospitals. [3,4]

Previously, data which truly reflect day to day practice have been limited, [5,6] therefore to further understanding, the REACH study was designed to provide current, real-life data on the clinical management of CAP and cSSTI in hospitals across Europe.[1,2,3,4] It was a retrospective, observational cohort study, involving a collaboration between independent experts and sponsored and funded by AstraZeneca.[1,2,3,4]

Results from REACH showed that mean rates of first-line treatment modification were 46.6 per cent for patients hospitalised with cSSTIs[1] and 37.1 per cent for patients hospitalised with CAP.[2] In addition, treatment modification rates were found to be even higher for patients with other existing illnesses. In cSSTI patients initial treatment modification rates increased to 49.3 per cent in patients with other illnesses compared with 37.1 per cent for those without.[1]

Although varying definition criteria were used, previous clinical studies investigating the treatment of cSSTI and CAP have found that treatment failure rates  ranged between 22 and 30 per cent in cSSTI [7, 8, 9, 10, 11, 12] and 2.4 and 31 per cent in CAP.[13]

These real world findings from REACH further add to the weight of evidence highlighting the challenges faced by physicians when initiating empiric antibiotic treatment for serious infections i.e. having to decide on the most appropriate antibiotic before the infecting pathogen can be diagnosed or confirmed. "We expected to see a certain level of first-line treatment modification, given the challenges physicians face when having to rapidly initiate treatment without a confirmed microbiological diagnosis, in these serious infections. However, the real world evidence in REACH showed there is a far greater need for treatment modification than may have been previously believed," said Principal Investigator of REACH Professor Francesco Blasi, University of Milan, Italy.

"The high initial treatment modification rates in REACH suggest that a reassessment of optimal management regimens of hospitalized CAP and cSSTI patients should be undertaken, particularly in those patients who have other underlying conditions that make them of additional concern to physicians."

Another important finding from the REACH study was an increase in the use of hospital resources associated with first-line treatment modification. Findings demonstrated that resource utilisation was increased in patients requiring treatment modification of their initial antibiotic, in comparison to those without, on a number of parameters, including length of stay in hospital, admission to the intensive-care unit and development of complications, for example, septic shock.[3,4]

Health Economist and REACH Principal Investigator Professor Helmut Ostermann, University Hospital Munich, Germany, said, "Both cSSTI and CAP can be associated with considerable morbidity and mortality, representing a heavy physical burden in terms of the health impact on the patient, and a significant economic problem as management is resource intensive and incurs high healthcare costs.  As we've seen in REACH, initial treatment modification was associated with an increase in the use of hospital resources, which highlights an opportunity to reduce costs if we can improve first-line treatment success."

John Rex, VP Clinical Infection, AstraZeneca commented: "The REACH study was designed specifically to create a better understanding of the clinical management of cSSTI and CAP in response to the current, real-world challenges in treating these infections. AstraZeneca is supporting REACH as part of our on-going commitment to improving the management of infectious diseases. AstraZeneca is continuing to invest in antibiotic research and development to address the danger posed to human health by such diseases and the growing threat of antimicrobial resistance."

NOTES TO EDITORS

About REACH

REACH was a retrospective, observational cohort study aiming to provide data on current clinical management of moderate to severe complicated skin and soft tissue infections (cSSTIs) and community-acquired pneumonia (CAP) in European hospitals.[1,2,3,4]

For cSSTI, the study included 1996 patients, from 129 sites in ten European countries, with the population comprised of patients >=18 years, hospitalised between March 2010 and February 2011 with a cSSTI requiring intravenous antibiotic treatment.[1]

For CAP, the study included 2039 patients from 128 centres in 10 European countries. Patients were >= 18 years old, hospitalised with CAP (2010-2011) and requiring treatment with intravenous antibiotics.[2]

Patients included in the study were selected using an automatic randomisation tool, in order to avoid selection bias.

The study was run by an independent academic steering committee and was a collaboration led by independent experts in infectious disease including, Professor Javier Garau, Professor Francesco Blasi and Professor Helmut Ostermann, sponsored and funded by AstraZeneca.[1,2,3,4]

Please note the figures in this press release reflect the data presented by the Principal Investigators at ECCMID 2012. Some figures vary slightly from the abstracts submitted to ECCMID in November 2011, owing to subsequent and final analysis of the REACH study data.

Initial Treatment Modification

In REACH, "initial treatment modification" was defined as the need for a change in first-line antibiotic treatment due to: [14, 15]

•    Insufficient response

•    Adverse reaction

•    Interaction with other drugs

•    Non-suitability of the initial antibiotic based on results of the microbiological tests

•    Changes to, or additions of, new agents in a subsequent line (alone or in combination)

•    Cases of patient death were also regarded as initial treatment modification

In REACH, initial treatment modification included "streamlining", also known as de-escalation, defined as change to narrower-spectrum antibiotics, upon patient improvement or confirmed microbiological diagnosis. This represents good clinical practice.

•    For patients hospitalised with cSSTI, the 46.6 per cent (n=930) mean treatment modification rate included a 5.6 per cent (n=112) streamlining of the overall study population[14]

•    For patients hospitalised with CAP, the 37.1 per cent (n=757) mean treatment modification rate included 5.1 per cent (n=105) streamlining of the overall study population[15]

Use of Hospital Resources

Figure 1. Use of resources depending on the need for treatment modification[3,4]

 
                                  cSSTI                                  CAP
                                                         
                         Without          Treatment           Without           Treatment
                        treatment       modification         treatment        modification
                      modification          (930            modification         (757
                         (1066            patients)            (1282            patients)
                       patients)                             patients)

    Total duration     14.7 (18.3)       24.5 (24.6)         10.9 (8.5)        15.3 (12.8)
    of
    hospitalisation,
    days, mean
    (median) 
                                                   
    Admission to the      3.7%              9.8%                 9.0%              21.3%
    intensive-care
    unit (per cent
    of patients)    
    Development of         4                 51                   20                64
    septic shock
    (number of
    patients)

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. Garau J, Blasi F, Medina J, Ávila M, McBride K, Ostermann H, et al. Current management of patients hospitalised with complicated skin and soft tissue infections across Europe (2010-2011): assessment of clinical practice patterns and real-life effectiveness of antibiotics (REACH study) [abstract]. In: 22nd European Congress of Clinical Microbiology and Infectious Diseases; March 2012.

2. Blasi F, Ostermann H, Medina J, Ávila M, McBride K, Garau J, et al. Current management of patients hospitalised with community-acquired pneumonia across Europe (2010-2011): assessment of clinical practice patterns and real-life effectiveness of antibiotics (REACH study) [abstract]. In: 22nd European Congress of Clinical Microbiology and Infectious Diseases; March 2012.

3. Ostermann H, Blasi F, Medina J, Pascual E, McBride K, Garau J, et al. Health economic analysis of current clinical management of patients hospitalised with complicated skin and soft tissue infections across Europe (2010-2011) (REACH study) [abstract]. In: 22nd European Congress of Clinical Microbiology and Infectious Diseases; March 2012.

4. Ostermann H, Blasi F, Medina J, Pascual E, McBride K, Garau J, et al. Health economic analysis of current clinical management of patients hospitalised with community-acquired pneumonia across Europe (2010-2011) (REACH study) [abstract]. In: 22nd European Congress of Clinical Microbiology and Infectious Diseases; March 2012.

5. 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.

6. Welte T, Torres A, Nathwani D. Clinical and economic burden of community acquired pneumonia among adults in Europe. Thorax published online August 20 2010.

7. 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 Feb;29(2):160-9.

8. Zilberberg MD, Shorr AF, Micek ST, Hoban AP, Pham V, Doherty JA, 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 Dec;30(12):1203-10.

9. Eagye KJ, Kim A, Laohavaleeson S, Kuti JL, Nicolau DP. Surgical site infections: does inadequate antibiotic therapy affect patient outcomes? Surg Infect (Larchmt ) 2009 Aug;10(4):323-31.

10. Zilberberg MD, Shorr AF, Micek ST, Chen J, Ramsey AM, Hoban AP, et al. Hospitalizations with healthcare-associated complicated skin and skin structure infections: impact of inappropriate empiric therapy on outcomes. J Hosp Med 2010 Nov;5(9):535-40.

11. Berger A, Oster G, Edelsberg J, Huang XY, Weber DJ. Consequences of failure of initial antibiotic therapy in acute bacterial skin and skin structure infections (ABSSSI) in US hospitals, 2000-2009. Presented at the IDSA meeting; Boston, US: Sept 20-23, 2011.

12. Tarricone R, Aguzzi G, Capone A, Caravaggi CM, Esposito S, Franzetti F, et al. How complicated skin and soft tissue infections are treated in Italy: economic evaluation of inpatient intravenous antibiotic treatment in seven hospitals. J Med Econ 2008;11(2):265-79.

13. Garcia-Vidal C, Carratala J. Early and late treatment failure in community-acquired pneumonia. Semin Respir Crit Care Med 2009 Apr;30(2):154-60.

14. Garau, J, Blasi F, Medina J, Ávila M, McBride K, Ostermann H, on behalf of the REACH study group. Current management of patients hospitalised with complicated skin and soft tissue infections across Europe (2010-2011): assessment of clinical practice patterns and real-life effectiveness of antibiotics (REACH study). Poster 689, presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), London, March 2012.

15. Blasi, F, Ostermann H, Medina J, Ávila M, McBride K, Garau J, on behalf of the REACH study group. Current management of patients hospitalised with community-acquired pneumonia across Europe (2010-2011): assessment of clinical practice patterns and real-life effectiveness of antibiotics (REACH study). Oral 174, presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), London, March 2012.