For today, the results of a small (but highly significant) human clinical trial using bacteriophages to treat drug-resistant bacterial infection. I came across it while reading a summary article in an online publication from Johns Hopkins University, describing the work of one of their alums who now conducts research at the University of California, San Diego.[i] I was so excited I immediately pulled up the full article that was published by the Infectious Disease Society of America.[ii]
You’ll remember from my previous posts on this subject (for 2 of many examples, look here and here), that bacteriophages are viruses that infect and kill specific bacteria. We are chock full of them: it’s a checks-and-balances system for our guts inhabitants. Back in April, 2020, I wrote about the history of phage research: they were first discovered in the early part of the 20th century and for a time, before the advent of antibiotics, were successfully used to treat numerous infections including dysentery and E.coli. Unfortunately, as is so often the case, the new-fangled antibiotics erased the medical profession’s memory of phages, and they were all but forgotten…until antibiotic resistance became a devastating problem in the world. As the Johns Hopkins article points out, “Common infections, such as pneumonia, staph, gonorrhea, and tuberculosis, are becoming resistant and very hard to treat.” The article points out that antibiotic resistance is, according to the World Health Organization, “…one of the biggest threats to global healthy, food security and development today.” The article goes on to say that according to the CDC, “…at least 2.8 million Americans become infected annually with antibiotic resistant organisms, resulting in more than 35,000 deaths…”
Here is the most depressing part of this paper: in almost 2 years, the researchers reviewed 785 requests for bacteriophage therapy (BT). The requests were matched with labs that are working on various phage therapies for specific types of infection, which narrowed the field down to 119 individuals. And then, the researchers were only permitted to use the treatment for those who were down to their last possible treatment under the “compassionate care act”: “As phage therapy remains experimental, each case required approval from the FDA under a single-use IND.” Thus, some of those 119 patients were not approved as they had infections for which there are not yet phage therapies developed – but also, many died before the phages could be administered. Because of FDA bureaucracy, there was a long period of time between the request and the actual administration of the phages (ranging from 28 days to 386 days, with a median of 170.5 days): “The process from identification of a potential patient to actual clinical phage administration under compassionate use indications is detailed in Figure 2 and, as noted earlier, involves a significant time lag.”
There are just no words…
The paper describes the responses of the first 10 patients treated (with a combination of antibiotics and BT). For the most part, patients were treated with IV BT. 7 of the 10 patients were successfully treated, 2 failed, and 1 had “uninterpretable” results. A couple of notes of interest:
Patient 2 had bacterial pneumonia. He was treated with IV BT alone for 8 weeks and was taken off antibiotics. He had no recurrence of the infection while on BT and was still in the clear 3 months later. The two failures were both cases of bacterial pneumonia, and the patients had “…chronic (>1 year) biofilm-based infections. We hypothesize that treatment failure may be related to poor biofilm penetration of the phages…” (For those not familiar with the term biofilm, it is a thin, slimy film of bacteria (and potentially other microbes) that adhere to a surface, like the plaque on teeth. Biofilms are hard to penetrate and treat, and thus, all kinds of pathogens can grow in them.)
The authors conclude by noting that many clinical trials are upcoming all over the world, and that ““…our experience with BT highlights the promise of BT for multiple clinical indications.” I have long told you that my psychic powers are telling me that phage therapy will someday soon become the new-old thing. Stay tuned on this one: I think we’ll see many more clinical trials in the near future.
[ii] Aslam S, Lampley E, Wooten D, Karris M, Benson C, Strathdee S, Schooley RT. Lessons Learned From the First 10 Consecutive Cases of Intravenous Bacteriophage Therapy to Treat Multidrug-Resistant Bacterial Infections at a Single Center in the United States. Open Forum Infect Dis. 2020 Aug 27;7(9):ofaa389. doi: 10.1093/ofid/ofaa389. PMID: 33005701; PMCID: PMC7519779.