Currently, polymyxin-based regimen is the most commonly used treatment for difficult-to-treat drug-resistant (DTR-AB) infections caused by A. baumannii. Two new antimicrobials have recently been approved: cifedorocol and Ilavacycline have been shown to be effective against DTR-AB. Recent clinical trials have shown that Cefiderocol may serve as a potential treatment option for patients with DTR-AB but Cefiderocol has a higher mortality rate [24–26]. Eravacycline is more commonly used for abdominal infections [27]. In contrast to the slow progress of antibiotics, bacteriophage therapy has made good progress. Recently, scientists discovered that the endolysins Ply6A3[28], LysSS and that of phage vB_AbaP_D2 all showed wide antibacterial capability [29, 30]. Studies have found that bacteriophage-resistant A. baumannii is due to the lack of GPI gene fragment, but loss of these receptors makes it re-sensitive to antibiotics agents, which provides a new direction for treating clinical drug-resistant bacteria [31].
Phage therapy is already being used in clinic treatment. Relevant literature reported that phages have been used in treating the infection of MDR P. aeruginosa or pandrug-resistant achromobacter xylosoxidans after lung transplantation[32, 33], the infection of Klebsiella pneumoniae after artificial knee replacement and A. baumannii infection in COVID-19 patients[10, 34]. Clinical trials of phage therapy for patients with urinary tract infection after transurethral resection of the prostate and phage therapy for P. aeruginosa infection in the burn wound has been carried out[35, 36]. In addition to using phage therapy alone, scientists are also trying to combine phage-antibiotic treatments, this combination has been demonstrated that can inhibit the resistance in bacteria appear. In the same time, there is a synergy between the phage and antibiotic [37–40].
Abp95 is a lytic myoviridae phage,which is isolated from hospital sewage. Abp95 possess a relatively small genome of 42kb and it shows satisfactory thermal stability from 20 centigrade to 60 centigrade. Interestingly, Abp95 shows a relative wide host range. 58 of 200 clinical isolates are sensitive to Abp95. These 58 sensitive hosts are from 6 different resources and belong to 8 different STs. Although the primary host AB2013−95 is an antibiotic-sensitive strain (Table 1), 55 of the 58 isolates are carbapenem-resistant A. baumannii strains.
About 6.3% of people with diabetes develop diabetic foot worldwidr, and at the infected diabetic foot ulcers, Staphylococcus aureus accounted for 42% [41], but A. baumannii is becoming one of the main bacteria in diabetic foot ulcers infections [42]. Diabetic patients suffer from shortage of tissue perfusion and limb necrosis due to microvascular disease, which obstructs the effect of active antibiotics against bacteria from chronic wound infection[41]. At the same time, due to the massive use of antibiotics, drug-resistant bacteria develop on such wounds. At present, the research and development rate of new antibiotics is significantly slower than the drug-resistant bacteria appear, and the hope of relying solely on antibiotics to treat infected wounds is becoming increasingly slim. Phage therapy has natural advantages, it is highly specific, and the dosage is small, moreover it can realize individualized design. In our diabetic wound models, Abp95 treatment did not reduce the survival rate of mice, proving that it has an acceptable safety profile. An acceleration of wound closure was observed by treating wounds topically with Abp95.
Nowadays, A. baumannii has undoubtedly become one of the most pan-drug resistant bacteria species. In the face of this situation, phage therapy is one of the most valuable treatment. Abp95 has a wide Host-Range, and 98% of them are CRAB, which has good resistance to drug-resistant A. baumannii, and we should conduct in-depth research on it in the future.