Table 1 Alternative technologies discussed in this paper

Antibiotic biomaterials

Antibiotic biomaterials are substances that are added to or form part of implants, prostheses, bandages or other medical devices in order to reduce the risk of bacterial infection. The working principle is that the biomaterial delivers an antibiotic drug over a prolonged time directly at the local site that is a risk of bacterial invasion and infection. There is inconclusive evidence on appropriate and optimal clinical use of this technology, and lack of standardized treatment protocols [85].

Antimicrobial nanoparticles

Nanoparticles are a drug delivery method that could be applicable for antibiotics. There are multiple working principles, including to improve the solubility of poorly water-soluble drugs; to prolong the half-life of drug systemic circulation by reducing immunogenicity; to release drugs at a sustained rate or in an environmentally responsive manner and thus lowers the frequency of administration; to deliver drugs in a target manner to minimize systemic side effects; and to deliver two or more drugs simultaneously for combination therapy to generate a synergistic effect and suppress drug resistance. There seems to be no nanoparticle based antibiotic therapies in clinical use [37, 106].

Antimicrobial peptides

These molecules are produced as part of the innate (non-specific) immune system which confers defense against infections without prior exposure to foreign pathogens. The working principle is that the peptides would disrupt cell membranes, with a broad spectrum effect on a variety of microbes, including bacteria. The exact mechanism of action is still unclear. Hence, the potential clinical utility of this technology is yet to be determined [72].

Anti-virulence materials

Therapeutic agents which target the mechanisms and processes through which microbes cause infection or a pathogenic cascade. In contrast to traditional antibiotics, the working principle is not to kill the pathogen, but to inhibit its capacity to cause illness. In other words, anti-virulence materials could prevent specific bacteria from adhering to human tissue, or inhibit bacterial quorum sensing or secretion of toxins, or make specific bacteria more sensitive to traditional antibiotics. Few, if any, antibacterial candidates have moved beyond animal model studies [107].

Bacteriophages (including lysins)

Bacteriophages are a type of virus that infects bacteria. The working principle of using bacteriophages as a therapeutic agent is that the phages would infect a pathogenic bacterial cell, whereupon they would replicate to synthesize genome and structural proteins into progeny virions inside the host cell. Finally the new phages would escape by rupturing the bacterial cell wall which results in the death of the cell. The escaping phages would in turn be capable of infecting other bacterial cells. Phages are highly bacteria-specific. This technology is in clinical use in some Eastern European countries, including Georgia, Poland, and Russia [70, 71].

Fecal microbiota transplantation (FMT)

FMT involves transplantation of feces from healthy donors into the gut of individuals with a gastrointestinal infection or condition. The working principle is that the bacteria from the donor would restore the microbiological environment in the patient’s intestines, thus eliminating the pathogenic bacteria. Clinical trials have demonstrated effect on Clostridium difficile infection, but standardized clinical protocols have yet to be developed [65].

Probiotics

Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. The working principle is similar to that of FMT in that the ingested microorganisms improve the function of the intestinal flora of the patient. Clinical trials studying the effect of probiotics against a variety of conditions have been carried out, including bacterial infections, with diverging results. As with FMT, standardized clinical protocols are not yet in widespread use [108]

Rapid point-of-care diagnostics

RPOCD are analytical testing performed outside the central laboratory, and can be based on a range of technologies, including antigen based tests, whole genome sequencing, real-time polymerase chain reaction, probe-based assays, bioluminescence real-time amplification, and microarray or micropump technologies. In a clinical perspective, the working principle is to use a device or devices that can be easily transported to the vicinity of the patient, with the benefit of rapid diagnosis and concurrent onset of appropriate treatment. In outpatient settings, RPOCD could provide access to diagnostics in resource constrained settings, or instant diagnosis could save the patient the delay caused by having to pay the clinic an additional visit to receive test results and the appropriate treatment [52].

Vaccines

A vaccine is a biological preparation that improves immunity to a particular microorganism. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The working principle is to stimulate the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters. Vaccines against a range of different viral and bacterial diseases are in widespread use [30].

Therapeutic antibodies

Antibodies are synthesized in the human body by the plasma cells as a response to an invading foreign agent. Monoclonal antibodies can be produced in cell culture, but antibodies can also be produced in vivo by extraction from blood material, for instance. The working principle of therapeutic antibodies is that when injected into the human body, the antibodies will bind to specific locations on specific microbial cells or proteins, thus facilitating the natural immune system in eliminating that cell or protein. Anti-microbial antibodies fall in two broad categories; those that bind directly to the pathogen, and those that aim to neutralize toxins or other virulence factors. There seems to be no antibodies based antibiotic therapies in clinical use [109].