The Northern Colorado Health Research Coalition held a meeting on Wednesday entitled “Translational Research – The Emergence of Drug Resistant Infectious Diseases.” The program offered both academic perspectives and ground-level efforts to test for and prevent some of these infections.
Indira Gujral, formerly the infection control coordinator at Medical Center of the Rockies (MCR) and now with the state health department, began the evening discussing methicillin-resistant Staphylococcus aureus (MRSA) and the efforts that have been made at prevention at MCR. Gujral called MRSA the “Marsha Brady of infectious disease” as it receives a majority of the attention when many other drug-resistant infections are also present challenges. Along with noting general hospital wide efforts (e.g. hand washing protocols), Gujral highlighted the program MCR implemented within the intensive care unit (ICU). An important distinction must be made between colonization – essentially carriers of MSRA – and those who are infected or symptomatic. MCR screens all patients entering the ICU via nasal swab to identify colonized patients. The hospital shoulders the $42 cost per cartridge to complete the test, as well as retesting initially negative patients after a week. All colonized patients are put in contact isolation including gown and glove requirements for staff coming in contact with the patients. Gujral encouraged those in attendance to consider additional research on MRSA in the community, especially group living settings such as skilled nursing and rehabilitation facilities, as less data exists about these settings. An additional challenge to controlling infection in long-term settings is that isolating people is not an option.
Jack Wheeler, VP of Business Development at Microphage, continued the discussion of MSRA focusing on his company’s new test in development. Microphage’s test can identify when an infection is staph and its resistance – or “what bug, what drug” – in about four hours after taking a blood sample. This far outpaces currently used Petri dish methods which may take up to 72 hours to identify resistance. This speed will enable more precise treatment rather than use of broad based antibiotics which can further compromise already sick patients and contribute to future drug resistance.
Microphage’s technology uses phages – viruses that replicate very rapidly inside bacteria – eventually bursting the host cell. Each phage is highly specific, only replicating in a specific type of bacteria. Microphage’s test takes advantages of the rapid and prolific replication of phages inside their chosen host bacterium. In the test, three types of phages that replicate in staph and a proprietary nutrient broth are added to the patient sample; if the bacteria in the sample are staph a measurable concentration of phages will exist after the four hour incubation period (measured with a lateral flow immunoassay). Simultaneously, in a separate test the patient sample is introduced to the three phages, proprietary broth, and an antibiotic. If a measurable concentration of phages appears in this test, the staph infection is MRSA (if susceptible, the bacteria would die before the phage can replicate). The company has seen impressive results in testing so far with both sensitivity and specificity exceeding 95% and hopes to be able to approach the FDA in about six months. Wheeler expects tests costs to come in under $20 per test, also noting that no additional capital is necessary to run the test.
Dr. Herbert Schweizer and Dr. John Belisle, both professors at CSU, split the last presentation slot of the evening covering “Emerging Challenges with Antimicrobial Resistance”. Schweizer focused on gram negative bacteria, for which few new treatments have been developed. He noted that bacterial resistance to antibiotics emerges via several different mechanisms:
- Exclusion – The bacterium prevents the antibiotic from entering
- Ezymatic inactivation – The bacterium is able to inactivate the antibiotic once in enters the cell (e.g. phosphorylation)
- Target alternation – The molecules that the antibiotic used to attack have changed
- Active efflux – The bacterium actively expels the antibiotic after it enters the cell
Gram negative bacteria present a special challenge because when their complex cell envelopes – which include a tough-to-penetrate outer layer not present in gram positive strains – are combined with active efflux, it is difficult to achieve therapeutic levels of antibiotic inside the bacteria. Schweizer coined handing this resistance in gram negative bacteria “the challenge of the decade” as few drugs are currently in development and those that are just represent new molecules within existing classes as opposed to entirely new chemotypes.
Belisle focused on resistant strains of tuberculosis, specifically Multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). While MDR-TB is resistant to both rifampicin and isoniazid, XDR-TB possesses these resistances along with resistance to a least one quinolone and one of the second-line injectable drugs. A key challenge to treating tuberculosis even in its non drug resistant form is that it requires an approximately six month course of treatment – a challenge well known to anyone with pills still in the medicine cabinet from their last 10 day course of antibiotic treatment. The challenge of enabling distribution of and access to this regimen is magnified in developing countries where infrastructure is lacking. Belisle highlighted the need to more easily identify TB susceptibility, ideally in the field, to enable effective treatment as current lab methods are beyond the reach of many areas.
NCHRC is a collaboration among the Poudre Valley Health System, the Colorado Bioscience Association, and Colorado State University. The next meeting will occur on March 31 and focus on gerontology.
