## 2 Antibofilm Peptides
### Antibioticfilm Peptides Tested In Vivo  
Despite a high interest in AMPs with antib biofilm properties, there have been only a few studies investigating their activity using in vivo models (Table 2). This may be explained by the lack of efficient animal models. To date, very few animal models are available that involve biofilm-associated infections and they are often inconsistent, technically challenging and self-limiting, frequently resolving without antibiotic treatment [66]. One of the drawbacks of antimicrobial peptides includes their enzymatic degradation. To overcome this limitation, several groups designed full D-enantiomeric peptides, which cannot be recognized by bacterial or host proteases that can cleave peptides composed entirely of L-amino acids [67]. In their study, [PERSON] et al. investigated potency of a D-enantiomeric peptide D-RR4 alone and in combination with colistin against _P. aeruginosa_ and _A. baumannii_ biofilms in vivo using the _C. elegans_ infection model [68]. D-RR4 produced a significant reduction in bacterial burden of _P. aeruginosa_ at 8 \(\times\) MIC (85%). Similarly, colistin (8 \(\times\) MIC) produced an 89% reduction in bacterial load. Complete clearance of bacteria from worms was achieved only when D-RR4 was combined with colistin. In case of colistin-resistant _P. aeruginosa_ isolated from a cystic fibrosis patient, treatment with D-RR4 resulted in 75% reduction. Combination of D-RR4 and colistin showed enhanced killing reducing 98% of colistin-resistant _P. aeruginosa_ in infected worms. Similar patterns were observed for _A. baumannii_ biofilm treatment. Additionally, D-RR4 significantly increased the survival rate of _Caenorhabditis elegans_ and gave nearly complete protection after 24 h for both pathogens. It is worth mentioning, that both the _C. elegans_ model and the _Galleria_ model are often used as established biofilm infection models [69; 70]. Another study also exploring the effect of D-enantiomer peptides tested DJK-5 and DJK-6 in both models in order to explore their activity against _P. aeruginosa_ biofilms [51]. Peptides IDR-1018 and RI-1018 (retro-inverse D-analog of IDR-1018) were also included in the study, however only RI-1018 managed to display protective effect in _Galleria mellonella_. On the other hand, DJK-5 and DJK-6 significantly protected both _C. elegans_ and _G. mellonella_ from _P. aeruginosa_ infections. Another peptide SAAP-148, formulated in ointment, effectively treated both acute and established (biofilm-associated) wound infections in mice caused by multi-drug resistant _S. aureus_ and _A. baumannii_ after a single 4 h treatment [71]. WRL3 also demonstrated antibiotic film activity against multi-drug resistant _S. aureus_ infection using a MRSA-infected burn wound model [72]. WRL3 was found to be able to control proliferation of MRSA in wound tissue as well as reduce bioburden and provided a more favorable environment for wound healing. Recently, [PERSON] et al. have developed a reproducible mouse model of cutaneous abscess infections and used it for testing IDR-1018 alongside with a new peptide 3002 [62]. After a single intra-abscession injection, the lesion size significantly reduced by 2.8-fold (for 3002) and 2.4-fold (for IDR-1018). Interestingly, neither peptide had any effect on the bacterial load recovered from the abscess suggesting that the decrease in abscess size may be due to antib Biofilm activity combined with additional immunomodulatory effects, induced by the peptides. Additionally, [PERSON] and his colleagues used the same in vivo model to demonstrate that both DJK-5 and DJK-6 peptides were able to treat cutaneous abscesses caused by both PAO1 strain and a clinical strain of _P. aeruginosa_ by decreasing skin lesion sizes and reduced bacteria load inside the abscess [65].