Adaptive Phage Therapy for the Prevention of Recurrent Nosocomial Pneumonia: Novel Protocol Description and Case Series

Abstract

Nowadays there is a growing interest worldwide in using bacteriophages for therapeutic purposes to combat antibiotic-resistant bacterial strains, driven by the increasing ineffectiveness of drugs against bacterial infections. Despite this fact, no novel commercially available therapeutic phage products have been developed in the last two decades, as it is extremely difficult to register them under the current legal regulations. This paper presents a description of the interaction between a bacteriophage manufacturer and a clinical institution, the specificity of which is the selection of bacteriophages not for an individual patient, but for the entire spectrum of bacteria circulating in the intensive care unit with continuous clinical and microbiological monitoring of efficacy. The study presents the description of three clinical cases of patients who received bacteriophage complex via inhalation for 28 days according to the protocol without antibiotic use throughout the period. No adverse effects were observed and the elimination of multidrug-resistant microorganisms from the bronchoalveolar lavage contents was detected in all patients. A decrease in such inflammatory markers as C-reactive protein (CRP) and procalcitonin was also noted. The obtained results demonstrate the potential of an adaptive phage therapy protocol in intensive care units for reducing the amount of antibiotics used and preserving their efficacy.

Does Phage Therapy Need a Pan-Phage?

“…Polyphage therapy has been applied either with fixed (pret-a-porter) formulations or with a mix of fixed and adapted phages (through adaptive phage therapy). Polyphage therapy has a broad spectrum, is more likely to overcome bacterial resistance, and is better at resolving polymicrobial infections and biofilms, but it is more complex to propagate and test before and after treatment, may interfere with off-target microbiota, may cause adverse effects, may require regular updates against circulating strains, and makes final drug approval extremely complicated due to current regulations [ 143 , 207 ].…”

“…Because polyvalent phages could be useful in chronic pulmonary infections like cystic fibrosis, which are often polymicrobial, an increasing number of research groups and private companies are investigating ways to broaden the range of hosts, reduce resistance to phages, and enhance the breakdown of biofilms [ 142 ]. A good paradigm is the “Adaptive Phage Therapy Protocol” that was created and applied by scientists of the Research and Production Centre (RPC) “Micromir”, in collaboration with clinicians of intensive care units (ICUs) of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology (FRCC ICMR), for the prevention and treatment of all ICU patients [ 143 ]. The protocol is based on the selection of clinical isolates every 30 days, which then are examined by RPC personnel for their sensitivity in the phages in its phage bank.…”

“…After the examination, the RPC propagates an adapted (see below) phage cocktail with an efficacy of at least 70% against each species of isolated bacteria and transfers the adapted cocktail to the FRCC ICMR in order to be applied to the ICU patients two to three times per day. The difference compared to the other therapeutic protocols lies is that the technology of the therapy implies the strict compliance of a set of bacteriophages to the needs of a particular ICU rather than a particular patient [ 143 ].…”