RESUMEN
A 30-year-old bombing victim with a fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term (>700 days) antibiotic therapy is treated with a pre-adapted bacteriophage along with meropenem and colistin, followed by ceftazidime/avibactam. This salvage therapy results in objective clinical, microbiological and radiological improvement of the patient's wounds and overall condition. In support, the bacteriophage and antibiotic combination is highly effective against the patient's K. pneumoniae strain in vitro, in 7-day mature biofilms and in suspensions.
Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Fracturas Óseas/microbiología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/terapia , Klebsiella pneumoniae/fisiología , Terapia de Fagos , Adulto , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Bacteriófagos/genética , Bacteriófagos/ultraestructura , Biopelículas/efectos de los fármacos , Ceftazidima/farmacología , Ceftazidima/uso terapéutico , Islas de CpG/genética , Combinación de Medicamentos , Farmacorresistencia Microbiana/efectos de los fármacos , Farmacorresistencia Microbiana/genética , Fracturas Óseas/complicaciones , Fracturas Óseas/diagnóstico por imagen , Genoma Viral , Humanos , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/diagnóstico por imagen , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Polimorfismo de Nucleótido Simple/genética , Proteómica , Replicón/genéticaRESUMEN
Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) USA300 and Pseudomonas aeruginosa PAO1 biofilm was developed. Treatment of 1-day and 3-day MRSA and PAO1 biofilms with antibiofilm peptide DJK-5 significantly and substantially reduced the bacterial burden. This model enabled the screening of synthetic host defense peptides, revealing their superior antibiofilm activity against MRSA compared to the antibiotic mupirocin. The model was extended to evaluate thermally wounded skin infected with MRSA biofilms resulting in increased bacterial load, cytotoxicity, and pro-inflammatory cytokine levels that were all reduced upon treatment with DJK-5. Combination treatment of DJK-5 with an anti-inflammatory peptide, 1002, further reduced cytotoxicity and skin inflammation.