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Gram-negative Bacterial Infections

There has been a worldwide increase in the number of infections caused by Gram-negative bacteria. In a study of 1265 intensive care units in 75 countries, Gram-negative bacteria were present in 62% of patients with an infection, while Gram-positive bacteria were present in 47% of patients.1

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Given the increasing danger posed by
infections caused by Gram-negative bacteria,
Cubist is proud to be a pioneer in developing
potential new treatments.

Gram-negative bacteria are highly adaptive pathogens that can develop resistance through several mechanisms.2-6 Resistant Gram-negative bacteria are a serious global public health concern , as noted in the recent U.S. Centers for Disease Control and Prevention (CDC) report Antibiotic Resistant Threats in the United States, 2013.

In the U.S., it has been estimated that as many as 2 million patients each year become infected with a bacterial infection that is resistant to antibiotics, with an estimated 23,000 deaths associated with these infections.7 The prevalence of resistant Gram-negative bacteria can vary at local, regional, national, and international levels.8

Antibiotic-resistant infections pose considerable challenges to the health care system in relation to diagnosis, treatment, and infection control, as well as considerable costs. In most cases, antibiotic-resistant infections require extended hospital stays, additional doctor visits and healthcare use. The estimates of the healthcare costs to the U.S. economy for antibiotic-resistant infections have ranged as high as $20 billion.7

Gram-negative bacteria are common causes of intra-abdominal infections (IAIs), urinary tract infections (UTIs), nosocomial pneumonia, and bacteremia.9 Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa) are important pathogens in the hospital setting, accounting for 27% of all pathogens and 70% of all Gram-negative pathogens causing healthcare-associated infections.9

Gram-negative bacteria are showing rising rates of resistance to current therapies. The production of extended-spectrum β-lactamase (ESBL) enzymes is a common mechanism of resistance. Although the prevalence of ESBL-producing E. coli can vary from country to country, resistance rates to many commonly used therapies have increased throughout the world.8, 10-15 Rates of ESBL-producing K. pneumoniae have risen substantially, with the result that these bacteria are increasingly resistant to widely used antimicrobials.16,17

P. aeruginosa is the most common Gram-negative cause of nosocomial pneumonia and the second most common cause of catheter-related UTIs in the U.S..9 P. aeruginosa has several mechanisms that can confer resistance.4,5 Resistance rates for P. aeruginosa to antimicrobials vary widely in Europe; rates are lowest (<10%) in the north and highest (25%-50%) in the south.10 In comparison, rates are intermediate in the U.S..9 Some P. aeruginosa can also be resistant to multiple classes of drugs. Reported rates of this multidrug-resistant (MDR) strain of P. aeruginosa can vary widely, but recent U.S. studies found that 17-22% of P. aeruginosa from patients with pneumonia and 14% from patients with UTI were MDR.9,18-20

E. coli is the most common cause of UTIs.9, 21-23 Cases of UTI caused by ESBL-producing E. coli and K. pneumonia as well as P. aeruginosa, including MDR strains, are increasing.19 ESBL-producing E. coli and K. pneumoniae are also frequently isolated in patients with complicated IAI (cIAI).24

P. aeruginosa is a problematic and virulent pathogen that can be a cause of common infections in humans such as nosocomial pneumonia, UTI, IAI, and bloodstream infections. P. aeruginosa is the most common Gram-negative organism causing ventilator associated pneumonia and the second most common cause of catheter-associated UTIs.9

The prevalence of P. aeruginosa in nosocomial pneumonia has recently been documented as 19% in the U.S. and 22.4% in other regions.25 Across several studies of cIAI, including peritonitis, P. aeruginosa has been isolated in 5%-17% of cases.26-31 In complicated UTI, P. aeruginosa has been found present in up to 13% of patients.32

The increase in the number of infections caused by Gram-negative bacteria is being accompanied by rising rates of resistance. Treatment options to meet this challenge are increasingly limited. There is a critical need for new antibiotics to meet the needs of patients now and in the future.


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  • Lu PL, Liu YC, Toh HS, et al. Epidemiology and antimicrobial susceptibility profiles of Gram-negative bacteria causing urinary tract infections in the Asia-Pacific region: 2009-2010 results from the Study for Monitoring Antimicrobial Resistance Trends (SMART). Int J Antimicrob Agents. 2012;40(Suppl):S37-S43.
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  • Babinchak T, Badal R, Hoban D, et al. Trends in susceptibility of slected Gram-negative bacilli isolated from Intra-abdominal infections in North America: SMART 2005-2010. Diagn Microbiol Infect Dis. 2013;76:379-81.
  • Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis. 2010;51(Suppl 1):S81-S87.
  • Augustin P, Dinh AT, Valin N, et al. Pseudomonas aeruginosa post-operative peritonitis: clinical features, risk factors, and prognosis. Surg Infect (Larchmt). 2013;14:297-303.
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  • Riché FC, Dray X, Laisné MJ, et al. Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis. Crit Care. 2009;13:R99.
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