Overview of Antibiotic Resistance

The antibiotic era began in 1928 with Fleming’s discovery of penicillin, but it wasn’t until 1944 that the drug was mass marketed. Just four years later, penicillin resistance was detected in Staphylococcus aureus. Streptomycin, discovered by Albert Schatz in 1943, was the first antibiotic to kill the tuberculosis bacillus, but monotherapy with streptomycin led to resistant organisms within months.  This is the unfortunate story of antibiotic therapy: protracted scientific development followed by the rapid evolution of microbial resistance.

The Centers for Disease Control and Prevention estimates that nearly 2 million patients in the United States acquire an infection in a hospital each year and about 90,000 die as a result of their infection. “More than 70% of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them. Persons infected with drug-resistant organisms are more likely to have longer hospital stays and require treatment with second- or third-choice drugs that may be less effective, more toxic, and/or more expensive.”

Table 1 illustrates this fact: bacteria are now resistant to many of our most powerful antibiotics.

Drug/Pathogen % Resistance
Methicillin / S. aureus 56
Vancomycin / E. faecium 80
3rd-gen. Ceph / E. coli 6
Fluoroquinolone / E. coli 25
3rd-gen. Ceph / K. pneumoniae 24
Imipenem / P. aeruginosa 25
4th-gen. Ceph / P. aeruginosa 11
Fluoroquinolone / P. aeruginosa 31
Table 1. Antibiotic resistance in device-associated healthcare-acquired Infections, 2006-7

The rise of antibiotic-resistant bacteria is a serious threat to public health, but very few new antibiotics are being developed. Only twelve new oral or IV antibiotics have been approved since 1998. Only two of these, linezolid and daptomycin, have novel mechanisms of action, and both are now used to treat enterococcal infections that are resistant to the previous “antibiotic of last resort,” vancomycin. Six antibiotics are under review at the FDA; none of these has a novel method of action.

Clearly, pharmaceutical innovation is not keeping pace with microbial evolution. Synereca’s drug discovery program has the potential to re-arm existing antibiotics and make them effective against resistant organisms.

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