Results and Discussion Part 2

Among the approaches described in reviews, antibiotics, antibiofilm molecules, biological agents (phages and derivatives) and nanotechnologies are the most studied, representing 68.4% of the results.

Conversely, in clinical trials we found less variability in the investigated antibacterial tools, for both prevention and eradication of infections. Specifically, 90.8% of these studies evaluated vaccines (or other immune system helpers) and antibiotics.

In spite of the research efforts to find innovative therapies to eradicate biofilms, clinical trials generally test traditional therapeutic and preventive approaches (58.5%). In particular, inhibition of biofilm formation and preventive approaches are usually preferred in the clinical practice. Vaccines against bacterial-related diseases represent the most tested approach (55.6%), followed by intensive antibiotic administration.

The elective approach to treat infections is the use of single or combined drugs. High doses and long administration periods (from weeks to years) are particularly common, but the eradication rate spans from 20 to 100% (data inferred from trials with published results). It is worth noting that better results, higher efficacy and percentages of success do not always correspond to higher doses or longer treatments; even the combined use of several different antimicrobials or anti-inflammatory molecules is not a guarantee of success. Such therapies have side effects and could promote the emergence of resistance, which is still an unmet clinical challenge [i]. Occasionally, these factors lead to patients withdrawing from trials due to the severe adverse reactions. Moreover, despite the precautionary measures and surveillance programs, infections can return after a long period of remission and an apparent resolution.

Non-conventional methods, such as the use of nanotechnology, are limited to 0.9% of the evaluated trials, reflecting the scarcity of new therapies that reach the market.

Clinical trials are time-consuming, expensive, and often hard for the patients and can fail for several reasons [ii]. In the specific case of trials that investigate antibiofilm strategies, low success rate is partly due to the fact that currently available in vitro and in vivo models are not predictive of biofilm outcomes [iii,iv].

Analyzing the trials with posted results, we observed that limited number of participants results in huge variance or poor representativeness, hampering the success of studies testing antibiofilm technologies. This is further complicated by the intrinsic and extreme variability of biofilms [v], which could be enhanced by host immune response, host variability, and interference with the microbiome. Furthermore, a small sample size often results in lack of appropriate controls.

Overall, the difficulties in recruiting and retaining participants due to the invasiveness of the treatments limits the value of these studies, which often do not yield definitive results.

In clinical studies, prevention is preferred over treatment. Established microorganism infections are harder to treat and sometimes the first stages of infections are asymptomatic. Treatment and biofilm removal entail invasive techniques, such as manual or hydro debridement, pulsed electrical fields, ultrasonication, and combinations of the aforementioned approaches. Physical or mechanical methods alone are often not effective in eradicating established biofilms and need to be combined with intensive antimicrobial therapies. This synergy could better prevent the spreading of infection and is best suited to lower the microbial load [vi].

Some of the retrieved reviews described more than one antibiofilm or antibacterial strategy, often not strictly related. These papers were included into the category “more than one technique”.

Finally, all the reviews or trials that didn’t fall into any of the previously described categories (e.g. backing soda, nutrients depletion, etc.) were included into “other” (4.1% of clinical trials and 3.6% of reviews).

In conclusion, we noticed a wide range of innovative strategies investigated in basic research studies compared with the smaller number of therapies evaluated in clinical trials.