Need for new drugs to tackle 'superbugs'
Antibacterials used to treat hospital-acquired infections, mostly targeting
gram-positive organisms such as MRSA, generate revenues of approximately $1.5
billion annually in the US alone. Although MRSA has grabbed the headlines,
more worrying is the emergence of MDR gram-negative organisms, resistant to
almost all currently available drugs - highlighting a crucial unmet need in
the market.
Nosocomial infections are infections acquired by patients in the hospital
setting. Across the US and Europe it is thought approximately five to 10% of
hospitalized patients develop a nosocomial infection during their stay, and
these infections often result in significant morbidity and mortality.
Datamonitor estimates that up to 3.7 million patients develop nosocomial
infections in an average year in the US alone.
Bacterial pathogens are the most common cause of nosocomial infections,
contributing significantly to the hospital antibacterial market's sales of
$6.7 billion in 2005. Among the 21 different classes of antibacterial drugs,
the classes that have clearly dominated in terms of both sales and volume use
include parenteral cephalosporins and parenteral broad-spectrum penicillins,
accounting for 21% and 15% of total sales in 2005, respectively.
Rise in multi-drug resistant bacterial strains
Overuse of broad-spectrum antibiotics, improved survival of critically ill
patients, the rising population of immuno-compromised patients and the rise in
use of indwelling medical devices have all contributed to the emergence of
difficult to treat strains such as methicillin resistant staphylococcus aureus
(MRSA) and vancomycin resistant enterococcus (VRE). In 2004 the National
Nosocomial Infections Surveillance system found that MRSA strains accounted
for almost 63% of all S. aureus infections in ICUs in the US. Increases in
MRSA rates have also been reported in Europe, with the highest rates - 44% -
being observed in the UK.
At the same time, Enterococcal infections have also become increasingly
difficult to treat. In addition to their intrinsic resistance to beta-lactam
antibiotics, the prevalence of VRE and aminoglycoside resistant E. faecalis
strains has also been on the increase. Furthermore, these organisms are
becoming increasingly resistant to most of the available antimicrobial agents,
as illustrated by the recent emergence of vancomycin-intermediate/resistant
strains of S. aureus. Clostridium difficile has also emerged as an important
nosocomial pathogen. New, more virulent strains, such as BI/NAP1, which
affects mainly Canada and the US, and a similar strain known as O27, observed
in the UK, are spreading faster and have a higher mortality rate than the
previously known strains.
While gram-positive organisms account for the majority of hospital acquired
infections, there has been a significant increase in multi-drug resistant
gram-negative bacteria such as extended-spectrum beta lactamase producing
Escherichia coli and Klebsiella pneumoniae. Worryingly, some strains of
Pseudomonas aeruginosa and Acinetobacter baumannii have become resistant to
all currently available antimicrobials. Since gram-negative organisms exhibit
intrinsic resistance to several antibiotics, additionally acquired resistances
leave very few options for treatment.
For patients who have acquired a nosocomial infection, empirical treatment is
initiated depending on the site of infection and the suspected organism.
Vancomycin in combination with agents to cover for potential gram-negative
organisms is the preferred choice of therapy, since gram-positive organisms
such as S. aureus and in particular MRSA account for the majority of surgical
site infections, blood stream infections and hospital acquired pneumonia. On
the other hand, urinary tract infections, which are predominantly caused by
gram negative organisms such as E. coli, are usually treated with monotherapy.
Datamonitor estimates that the annual antibiotic spend for nosocomial
infections in the US ranges from $550 million for urinary tract infections, to
$250 million for bloodstream infections.
Lack of effective products
Due to the rising rates of multi-drug resistant gram positive bacterial
infections, the majority of newly introduced products and products in late
stage development target bacteria such as MRSA. Among the antibacterials
introduced since 2000 targeting such pathogens, linezolid (Zyvox) has been the
most successful, owing to its parenteral and oral formulations.
However, the MRSA market is likely to become increasingly crowded with drugs
such as daptomycin, launched in 2003, tigecycline, launched in 2005, as well
as dalbavancin and telavancin, both expected in 2007, intensifying the
competition. Tigecycline has generated much enthusiasm due to its ability to
target both gram-positive and gram-negative organisms; its disadvantage being
the lack of coverage for pseudomonas infections.
Although these new agents targeting gram-positive organisms have been welcomed
by the infectious disease community, there is a significant opportunity for
new antibacterials which can treat multi-drug resistant gram-negative
organisms - a crucial unmet need for the hospital market. Among pharma
companies active in the market for systemic antibiotics, Johnson & Johnson
appears to be the first to have spotted this gap. It looks best positioned
here with two in-licensed compounds, doripenem from Shionogi and ceftobiprole
from Basilea, both of which have already been filed for approval with the FDA.
Related research:
Stakeholder Opinions: Nosocomial Infections - The need for new gram-negative
drugs
Commercial Insight: Antibacterials - Growth in resistance rates drives niche
indications
Stakeholder Insight: Respiratory Tract Infections in the USA - The demise of
narrow-spectrum antibiotics
