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Abstract Background Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility. Methods This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log10 beginning with 4 × 107 plaque-forming units in an unblinded stage 1. If no serious adverse events related to the study product are identified, the trial will proceed to a double-blinded stage 2. In stage 2a, 32 participants will be randomly assigned to one of three phage dosages or placebo in a 1:1:1:1 allocation. An interim analysis will be performed to determine the phage dosage with the most favorable safety and microbiological activity profile to inform phage dosing in stage 2b. During stage 2b, up to 32 additional volunteers will be randomized 1:1 to the phage or placebo arm. Primary outcomes include (1) the number of grade 2 or higher treatment-emergent adverse events, (2) change in log10 P. aeruginosa total colony counts in sputum, and (3) the probability of a randomly selected subject having a more favorable outcome ranking if assigned to receive phage therapy versus placebo. Exploratory outcomes include (1) sputum and serum phage pharmacokinetics, (2) the impact of phage on lung function, (3) the proportion of P. aeruginosa isolates susceptible to the phage mixture before and after study product administration, and (4) changes in quality of life. Discussion This trial will investigate the activity of phages in reducing P. aeruginosa colony counts and provide insights into the safety profile of phage therapy. Trial registration ClinicalTrials.gov NCT05453578. Registered on 12 July 2022.

Abstract Background To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals. Methods Three hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing isolates. Susceptibility testing was performed by broth microdilution, and minimum inhibitory concentrations (MICs) interpreted per EUCAST breakpoints. Carbapenemase-, aminoglycoside modifying enzyme- and 16S rRNA methylase- encoding genes were detected by PCR. Results Of 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at ≤2 mg/L, with MIC50/MIC90 of 0.5/4 mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at ≤8 mg/L and was the second most active drug after plazomicin, followed by gentamicin (S, 43%; MIC50/MIC90, 4/> 256) and amikacin (S, 18.0%; MIC50/MIC90, 32/128). Twenty-three (7.7%) isolates (16 KPC-, 6 VIM- and one KPC & OXA-48-producers) exhibited MICs ≥64 mg/L for plazomicin, and harbored rmtB (n = 22) or armA (n = 1). AAC(6′)-Іb was the most common aminoglycoside modifying enzyme (84.7%), followed by AAC(3΄)-IIa (25.3%), while those two enzymes were co-produced by 21.4% of the isolates. Conclusions Plazomicin retains activity against most carbapenemase-producing K. pneumoniae isolated from Greek hospitals, with MICs consistently lower than those of the other aminoglycosides, even in the presence of aminoglycoside modifying enzymes. Dissemination of 16S- rRNA methylases in 8% of the isolates is an unwelcome event that needs strict infection control measures and rigorous stewardship interventions.

Many different tumor-targeted strategies are under development worldwide to limit the side effects and improve the effectiveness of cancer therapies. One promising method is to enhance the radiosensitization of the cancer cells while reducing or maintaining the normal tissue complication probability during radiation therapy using metallic nanoparticles (NPs). Radiotherapy with MV photons is more commonly available and applied in cancer clinics than high LET particle radiotherapy, so the addition of high-Z NPs has the potential to further increase the efficacy of photon radiotherapy in terms of NP radiosensitization. Generally, when using X-rays, mainly the inner electron shells are ionized, which creates cascades of both low and high energy Auger electrons. When using high LET particles, mainly the outer shells are ionized, which give electrons with lower energies than when using X-rays. The amount of the produced low energy electrons is higher when exposing NPs to heavy charged particles than when exposing them to X-rays. Since ions traverse the material along tracks, and therefore give rise to a much more inhomogeneous dose distributions than X-rays, there might be a need to introduce a higher number of NPs when using ions compared to when using X-rays to create enough primary and secondary electrons to get the desired dose escalations. This raises the questions of toxicity. This paper provides a review of the fundamental processes controlling the outcome of metallic NP-boosted photon beam and ion beam radiation therapy and presents some experimental procedures to study the biological effects of NPs’ radiosensitization. The overview shows the need for more systematic studies of the behavior of NPs when exposed to different kinds of ionizing radiation before applying metallic-based NPs in clinical practice to improve the effect of IR therapy.

Following publication of the original article [1],

Until recently, chemotherapy for metastatic melanoma had disappointing results. The identification of immune checkpoints such as CTLA-4 and PD-1/PD-L1 has led to the development of an array of monoclonal antibodies (Mabs). These immunologic approaches against tumoral cells come with a novel kind of side effects that the clinician needs to be familiarized with. Herein, we report for the first time a case of organizing pneumonia, based on imaging and cytological analyses of bronchoalveolar lavage, possibly associated with the use of pembrolizumab, an anti-PD-1 Mab recently approved for the treatment of metastatic melanoma.

Until recently, chemotherapy for metastatic melanoma had disappointing results. The identification of immune checkpoints such as CTLA-4 and PD-1/PD-L1 has led to the development of an array of monoclonal antibodies (Mabs). These immunologic approaches against tumoral cells come with a novel kind of side effects that the clinician needs to be familiarized with. Herein, we report for the first time a case of organizing pneumonia, based on imaging and cytological analyses of bronchoalveolar lavage, possibly associated with the use of pembrolizumab, an anti-PD-1 Mab recently approved for the treatment of metastatic melanoma.

Review of Teaching Business Information Literacy (ed. Snipes, Karo, Faulkner, & Reiter; published by Association of College and Research Libraries, 2022).