Standardized bacteriophage purification for personalized phage therapy. Nature protocols The world is on the cusp of a post-antibiotic era, but researchers and medical doctors have found a way forward-by looking back at how infections were treated before the advent of antibiotics, namely using phage therapy. Although bacteriophages (phages) continue to lack drug approval in Western medicine, an increasing number of patients are being treated on an expanded-access emergency investigational new drug basis. To streamline the production of high-quality and clinically safe phage preparations, we developed a systematic procedure for medicinal phage isolation, liter-scale cultivation, concentration and purification. The 16- to 21-day procedure described in this protocol uses a combination of modified classic techniques, modern membrane filtration processes and no organic solvents to yield on average 23 mL of 10 plaque-forming units (PFUs) per milliliter for Pseudomonas, Klebsiella, and Serratia phages tested. Thus, a single production run can produce up to 64,000 treatment doses at 10 PFUs, which would be sufficient for most expanded-access phage therapy cases and potentially for clinical phase I/II applications. The protocol focuses on removing endotoxins early by conducting multiple low-speed centrifugations, microfiltration, and cross-flow ultrafiltration, which reduced endotoxins by up to 10-fold in phage preparations. Implementation of a standardized phage cultivation and purification across research laboratories participating in phage production for expanded-access phage therapy might be pivotal to reintroduce phage therapy to Western medicine. 10.1038/s41596-020-0346-0

Acinetobacter baumannii: More ways to die. Microbiological research Acinetobacter baumannii is an important nosocomial and opportunistic pathogen. It causes infections worldwide, especially in intensive care units. It is clinically significant owing to its ability to persist for long periods on surfaces, as well as its resistance to multiple antibiotics. This pathogen has been reported to defy the available therapeutic options to combat it. In this dire circumstance, the need for new approaches to treating A. baumannii infections is undeniable. In this minireview, we summarize three important treatment options for controlling A. baumannii pathogen, including the use of bacteriophage / bacteriophage cocktails, phage-antibiotic combinations and resistance-driven fitness losses. It is hoped that, as resources to treat its infection expand, A. baumannii can become less scary. 10.1016/j.micres.2022.127069

Novel antimicrobial agents for combating antibiotic-resistant bacteria. Advanced drug delivery reviews Antibiotic therapy has become increasingly ineffective against bacterial infections due to the rise of resistance. In particular, ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have caused life-threatening infections in humans and represent a major global health threat due to a high degree of antibiotic resistance. To respond to this urgent call, novel strategies are urgently needed, such as bacteriophages (or phages), phage-encoded enzymes, immunomodulators and monoclonal antibodies. This review critically analyses these promising antimicrobial therapies for the treatment of multidrug-resistant bacterial infections. Recent advances in these novel therapeutic strategies are discussed, focusing on preclinical and clinical investigations, as well as combinatorial approaches. In this 'Bad Bugs, No Drugs' era, novel therapeutic strategies can play a key role in treating deadly infections and help extend the lifetime of antibiotics. 10.1016/j.addr.2022.114378