Multi-drug-resistant organisms (MDRO), in general, refer to bacteria that are not affected by the clinical doses of classical antibiotics, in particular, the antibiotics used to treat them until recently. The rise of these organisms has created a need for alternative antibacterial therapies.
Resistance-modifying agents
One solution to combat resistance currently being researched is the development of pharmaceutical compounds that would revert multiple antibiotic resistance. These so-called resistance-modifying agents may target and inhibit MDR mechanisms, rendering the bacteria susceptible to antibiotics to which they were previously resistant. These compounds' targets include among others
Phage Therapy
Phage therapy, the use of a particular group of viruses capable of invading bacteria known as phages to treat bacterial infections. Phage are commonly a part of the ecology surrounding bacteria and provide substantial population control of bacteria in the intestine, the ocean, the soil, and other environments. The therapy was in use during the 1920s and 1930s on humans in the US, Western Europe, and Eastern Europe. The success of these therapies is largely anecdotal, and rigorous scientific studies in the form of clinical trials commonly used to evaluate the efficacy of new medications on the efficacy of phage therapy are limited The original publications into phage therapy are also generally inaccessible, even to persons with Russian language fluency. With the discovery of penicillin in the 1940s, Europe and the US abandoned research into phage therapy and began work to develop antibiotics as a therapeutic strategy combate bacterial infections. However, in the former Soviet Union, phage therapies continued to be studied in the Eliava Institute of Bacteriophage, Microbiology & Virology, Republic of Georgia.With the development of antibiotic-resistant bacteria, there was a renewed interest in development of phage therapy as a viable alternative to antibiotic treatment of bacterial infection in western medicine. Research is currently ongoing; companies (Intralytix, Novolytics, UK, Gangagen, India), universities, and foundations in North America and Europe are currently researching phage therapies. However, concerns about genetic engineering in freely released viruses currently limit certain aspects of phage therapy. One result is attempts to use phage in ways other than to directly infect the bacteria. While bacteriophage and related therapies provide a possible solution to aspects of antibiotic resistance, much more research is needed to realise their potential
Bacteriocins
Bacteriocins are also a growing alternative to the classic small-molecule antibiotics. Different classes of bacteriocins have different potential as therapeutic agents. Small molecule bacteriocins (microcins, for example, and lantibiotics) may be similar to the classic antibiotics; colicin-like bacteriocins are more likely to be narrow-spectrum, demanding new molecular diagnostics prior to therapy but also not raising the spectre of resistance to the same degree. One drawback to the large-molecule antibiotics is that they have relative difficulty crossing membranes and travelling systemically throughout the body. For this reason, they are most often proposed for application topically or gastrointestinally. Because bacteriocins are peptides, they are more readily engineered than small molecules. This may permit the generation of cocktails and dynamically improved antibiotics that are modified to overcome resistance.
Nutrient withdrawal
Nutrient withdrawal is a potential strategy for replacing or supplementing antibiotics. The restriction of iron availability is one way the human body limits bacterial proliferation. Mechanisms for freeing iron from the body (such as toxins and siderophores) are common among pathogens. Building on this dynamic, various research groups are attempting to produce novel chelators that would withdraw iron otherwise available to pathogens (bacterial,fungal and parasitic ). This is distinct from chelation therapy for conditions other than bacterial infections - including successful treatment for iron overload.
Vaccines
Vaccines are a commonly suggested method for combating MDRO infections. They actually fit within a larger class of therapies that rely on immune modulation or augmentation. These therapies either excite or reinforce the natural immune competency of the infected or susceptible host, leading to the activity of macrophages, the production of antibodies, inflammation, or other classic immune reactions.
Just as the macrophage engulfs and consumes bacteria, various forms of biotherapy have been suggested that employ organisms to consume the pathogens. This includes the employment of protozoa and maggot therapy.
Probiotics
Probiotics are another alternative that goes beyond traditional antibiotics by employing a live culture, which may, in theory, establish itself as a symbiont—competing, inhibiting, or simply interfering with colonization by pathogens.
