Combatting Antibiotic Resistance

Why P128 is needed

Superbugs are an increasing menace both in hospitals and in the community. GangaGen’s P128 is being developed to prevent or treat serious, and often fatal infection by MRSA, which is a ‘Superbug’, resistant to multiple antibiotics. Legislation at the national level in Europe and the state level in the United States mandating control of Superbugs is becoming more and more common. S. aureus , which over the decades has become resistant to a large number of antibiotics, is one such target of these mandates.

Staphylococcus aureus causes a range of illnesses, from minor skin infections, such as pimples, impetigo, boils, cellulitis, folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome, bacteremia, and sepsis. Also, it is one of the most common causes of hospital acquired infections (HAIs) and is often the cause of postsurgical wound infection. S. aureus was the first among ten most common pathogens causing device and procedure related Hospital associated infections (HAIs) during 2006-7 as reported by hospitals in the National Healthcare Safety Network (NHSN), USA. Staphylococcal infection especially MRSA, has shown significant rise in the incidence in Asia. The regional Resistance Surveillance (RSS) programme showed that 73% of the clinical S. aureus isolates from two hospitals in Korea were MRSA in 2011. The SENTRY studies in China showed MRSA in 13 to 27.8% of clinical S. aureus isolates from three hospitals in 1998-2001; however rates increased to 50–62% in 2004–2005. The nationwide surveillance study in 2011 showed a mean MRSA incidence rate of 45.8% among all clinical S. aureus isolates. The ANSORP study showed MRSA rates of 38.1% for the Philippines, 57% for Thailand and 74.1% for Vietnam in 2004–2006

Methicillin-resistant Staphylococcus aureus (MRSA) was first described in 1961. Shortly thereafter, outbreaks of MRSA were reported in early 1960s from many places. Since then, MRSA has spread worldwide, and the prevalence of MRSA has exponentially increased in both healthcare and community settings. HAIs infections due to methicillin resistant strains of S. aureus amounted to 60% in ICUs in US during 2003 and more than 90,000 invasive infections were estimated to be MRSA during the 18 month period of 2004 to 2005. A substantial proportion of cases of S. aureus blood infection appear to be of self origin given that they disseminate from the patient’s nose. About 30-50% of the population carries S. aureus in their nares. The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and clearing the organism from their nose. This reduces the risk of infection and the resultant hospitalization and treatment costs.

The first case of vancomycin-intermediate-resistant S. aureus (VISA) was identified in 1997, and such strains have now been reported worldwide. More recently, there have been reports of vancomycin resistant S.aureus (VRSA), which is even more alarming, as these isolates demonstrate complete vancomycin resistance.

Linezolid, is one of the few therapeutic options shown to be effective against MRSA. In 2001, one year after linezolid was approved for clinical use, the first Linezolid Resistant Staphylococcus aureus (LRSA) was reported in a US patient. Since then, several cases of LRSA have been reported.

Whereas previously only regarded as an innocuous commensal microorganism on the human skin, Staphylococcus epidermidis is nowadays seen as an important opportunistic pathogen. It is now a frequent cause of nosocomial infections, at a rate about as high as that due to its more virulent cousin Staphylococcus aureus. In particular, S. epidermidis represents the most common source of infections on indwelling medical devices. This likely stems from the fact that S. epidermidis is a permanent and ubiquitous colonizer of human skin, and the resulting high probability of device contamination during insertion. While S. epidermidis infections only rarely develop into life-threatening diseases, their frequency and the fact that they are extremely difficult to treat represent a serious burden for the public health system. The costs related to vascular catheter-related bloodstream infections caused by S. epidermidis amount to an estimated $ 2 billion annually in the United States alone.

Drug-resistant strains among coagulase-negative staphylococci (CoNs), including S. lugdenensis, S. haemolyticus and S. epidermidis are reported both inside and outside the hospital environment. These represent upcoming challenges as these Staphylococci are capable of causing serious infections.

With the increasing drug resistance among Staphylococci, new classes of antimicrobial agents with different mechanisms of action are urgently required.