Determination of phage susceptibility as a clinical diagnostic tool: A routine perspective.

As the global burden of disease caused by multidrug resistant bacteria is a major source of concern, credible clinical alternatives to antibiotic therapy, such as personalized phage therapy, are actively explored. Although phage therapy has been used for more than a century, the issue of an easy to implement diagnostic tool for determining phage susceptibility that meets current routine clinical needs is still open. In this Review, we summarize the existing methods used for determining phage activity on bacteria, including the three reference methods: the spot test, the double agar overlay plaque assay, and the Appelmans method. The first two methods rely on the principle of challenging the overnight growth of a lawn of bacteria in an agar matrix to a known relative phage to bacteria concentration and represent good screening tools to determine if the tested phage can be used for a "passive" and or "active" treatment. Beside these methods, several techniques, based on "real-time" growth kinetics assays (GKA) have been developed or are under development. They all monitor the growth of clinical isolates in the presence of phages, but use various detection methods, from classical optical density to more sophisticated techniques such as computer-assisted imagery, flow-cytometry, quantitative real-time polymerase chain reaction (qPCR) or metabolic indicators. Practical considerations as well as information provided about phage activity are reviewed for each technique. Finally, we also discuss the analytical and interpretative requirements for the implementation of a phage susceptibility testing tool in routine clinical microbiology.

Oral Intake of Lactobacilli Can Be Helpful in Symptomatic Bacterial Vaginosis: A Randomized Clinical Study.

OBJECTIVE: The aim of the study was to explore a role of oral intake of a mixture of 3 Lactobacillus species in recurrence of bacterial vaginosis (BV). MATERIALS AND METHODS: A phase 2 randomized parallel group prospective placebo-controlled study conducted at 7 clinical centers enrolled 18- to 45-years-old women with recent symptomatic BV cured with metronidazole. Within 48 hours after completion of metronidazole therapy, eligible women received 1 capsule of the verum (5.4 billion Lactobacillus crispatus LMG S-29995, Lactobacillus brevis, and Lactobacillus acidophilus in proportion of 60%, 20%, and 20%, respectively), or the placebo supplement 2 times daily for the first 7 days and 1 time daily for the next 8 to 120 days. The primary outcome measure was the percentage of recurrence of BV, which was defined as 3 of 4 Amsel criteria plus abnormal vaginal discharge/vulvar odor during 4 months of intake of the test dietary supplement. Differences between the groups were assessed with Z test for proportions. RESULTS: One hundred sixty-six women were analyzed in the verum (82 patients) and the placebo group (82 patients). Recurrence of BV was documented in 15 (18.3%) of 82 women in the verum group and 27 (32.1%) of 84 in the placebo group (p = .014). Rates of survival without BV rates were higher in the verum group (Cox F test, p = .018). Both verum and placebo supplements were well tolerated. CONCLUSIONS: Oral intake of L. crispatus LMG S-29995, L. brevis, and L. acidophilus can significantly decrease percent of recurrences of BV in recently treated women and prolong time to recurrence of the disease.