The high bacterial strain specificity of<unk>  may make it necessary for clinics to make different cocktails for treatment of the same infection or disease because the bacterial components of such diseases may differ from region to region or even person to person. In addition, this means that "banks" containing many different<unk> s must be kept and regularly updated with new<unk> s. Further, bacteria can evolve different receptors either before or during treatment. This can prevent<unk> s from completely eradicating bacteria. The need for banks of<unk> s makes regulatory testing for safety harder and more expensive under current rules in most countries. Such a process would make the large-scale use of<unk>  difficult. Additionally, patent issues (specifically on living organisms) may complicate distribution for pharmaceutical companies wishing to have exclusive rights over their "invention", which would discourage a commercial corporation from investing capital in this. As has been known for at least thirty years, mycobacteria such as Mycobacterium tuberculosis have specific bacteriophages. No lytic<unk>  has yet been discovered for Clostridium difficile, which is responsible for many nosocomial diseases, but some temperate<unk> s (integrated in the genome, also called lysogenic) are known for this species; this opens encouraging avenues but with additional risks as discussed below. The negative public perception of viruses may also play a role in the reluctance to embrace<unk> . Development of resistance One of the major concerns usually associated with<unk>  is the emergence of<unk> -insensitive mutants (BIMs) that could hinder the success of this therapy. In fact, several in vitro studies have reported a fast emergence of BIMs within a short period of time after<unk>  treatment. The emergence of BIMs has also been observed in vivo using different animal models, although usually occurs later than in vitro (reviewed in ). This fast adaptation of bacteria to<unk>  attack is usually caused by mutations on genes encoding<unk>  receptors, which include lipopolysaccharides (LPS), outer membrane proteins, capsules, flagella, pili, among others. However, some studies suggested that when<unk>  resistance is caused by mutations in<unk>  receptors, this might result in fitness costs to the resistance bacterium, which will ultimately become less virulent. Moreover, it has been shown that the evolution of bacterial resistance to<unk>  attack changes the efflux pump mechanism, causing increased sensitivity to drugs from several antibiotic classes. Therefore it is conceivable to think that<unk>  that uses<unk> s that exert selection for MDR bacteria to become antibiotic sensitive could potentially reduce the incidence of antibiotic resistant infections. Besides the prevention of<unk>  adsorption by loss or modification of bacterial receptors,<unk> -insensitivity can be caused by: (i) prevention of<unk>  DNA entry by superinfection exclusion systems; (ii) degradation of<unk>  DNA by restriction-modification systems or by CRISPR-Cas systems; and (iii) use of abortive infection systems that block<unk>  replication, transcription or translation, usually in conjugation with suicide of the host cell. Altogether, these mechanisms promote a quick adaptation of bacteria to<unk>  attack and therefore, the emergence of<unk> -resistance mutants is frequent and unavoidable. It is still unclear whether the wide use of<unk> s would cause resistance similar to what has been observed for antibiotics. In theory this is not very likely to occur, since<unk> s are very specific and therefore their selective pressure would affect a very narrow group of bacteria. However, we should also consider the fact that many<unk>  resistance systems are mounted on mobile genetic elements, including prophages and plasmids, and thus may spread quite rapidly even without direct selection. Nevertheless, in contrast to antibiotics,<unk>  preparations for therapeutic applications are expected to be developed in a personalized way because of the high specificity of<unk> s. In addition, strategies have been proposed to counter the problem of<unk>  resistance. One of the strategies is use of<unk>  cocktails with complementary host ranges (different host ranges, which - when combined - result in an overall broader host range) and targeting different bacterial receptors. Another strategy is the combination of<unk> s with other antimicrobials such as antibiotics, disinfectants or enzymes that could enhance their antibacterial activity. The genetic manipulation of<unk>  genomes can also be a strategy to circumvent<unk>  resistance.
Phage therapy
Music therapy
Aquatic therapy
Ultraviolet light therapy
Dance therapy
Virotherapy
Goeckerman therapy
Metaphor therapy