As soon as drugs like Kalydeco became available, my focus on CF turned to MDR or Multiple Drug Resistant bacteria, same thing as Pan-Resistant Bacteria. Personally I like the term you use, it's shorter and more inclusive. What you have left after a genetic drug arrests the symptoms of CF are pan-resistant infections, and the unrecoverable damage done by them. I'm not alone in changing my focus. Novel repurposing of older infection fighting methods have opened opportunities for small, custom approaches to MDR infections.
In a recent post titled "FEV1 and Oxygen needs", you can find it by Searching the title or find it in "Adults". The person who initiated the thread is culturing infections that are resisting the absolute most recent antibiotics. I believe you will get some encouragement by checking it out.
By definition MDR infections are virtually incurable with antibiotics, or antibiotics alone. Potentiators like steroids, stimulants like epinephrine and super solvents can make a difference. It's surprisingly simple and brilliant how multiple antibiotic therapy came to be. Between 1918 and 1945 the first 3 classes of antibiotics were developed. The first was a red fabric dye made by Bayer Chemical. Observation of women working with the dye were beating the 50-50 odds of postpartum death at the time. Gerhard Domagk was doing TB research even as the Allies were bombing the facility. Domagk had lost his wife from postpartum sepsis and was obsessed with a cure. TB was still killing more soldiers than wounds in WWI and combined with the Spanish Flu pandemic, the war could be won or lost by curing TB. Domagk wasn't a flash in the pan, in fact the pioneers of antibiotics had the follow through to solve the enormous amounts of antibiotics needed and microbiology was born.
TB to date has killed more people than any other disease in history. The first antibiotic was a sulfa drug discovered by Domagk, turning its grateful patients red. It all but eliminated postpartum sepsis and helped with TB, for a while. TB always came back and the antibiotic became ineffective. Penicillin had no effect but streptomycin and another class of antibiotic also worked, but none completely eradicated the TB.
It seems obvious now but antibiotics weren't really well understood and giving multiple antibiotics was met with resistance. We understand the mechanism behind each antibiotic today and with the ability to sequence the genome of a bacteria in hours, we should be able to make designer antibiotics, or give the perfect cocktail of antibiotic agents. Someday we will have this ability.
One confounding problem with many super bugs is the ability to create and live within a biofilm. Pseudomonous a. or such acts like individual actors in relatively low population concentration, non-mucoid form is like a swimmer in the lake, it's only influence is disturbing the water with the action of swimming. When bacteria have the ability to go between a mucoid and non-mucoid state, the ideal time is to catch it is during the non-mucoid state. When the population density reaches a certain point, the bacteria begin to act as a hive, a number of plasmids, genetic snippets that it sweats and absorbs causes the bacteria to create a slime that operates like a safe haven, keeping antibiotics out and food abounds. Limiting new infection, new drugs are making the hyper-viscous mucus from CF thin, and stuff like anti-infectives, identify and possibly provide the molecules to eradicate one infection in one person.
In the post "FEV1 and Oxygen needs the", I described Anti-infectives and gave a link to the topic. Anti-infectives are the next thing beyond antibiotics and a viable option when antibiotics fail us. These are living organisms, as small as a mold spore but more often something a little bit bigger like a nematode. They are able to be used to isolate a custom antibiotics or even used by directly infecting a person with the nematodes. You might want to read "Gut", a book review on it is on this site's main page. Autoimmune problems come to mind when I see someone with many different infections. It has some relevance when we start losing the battle with every infection.
By taking a careful step outside the box of conventional medical methods, you can find legitimate and effective treatments. I enjoy learning the history of science and medicine. Most seminal discoveries have an element of luck. I would agree but add it often takes furious gambling to get lucky. Indeed sloppy housekeeping is credited for seeing the TB bacillus. Carbolic acid was the standard antiseptic for cleaning up bacterial cultures and open tubs of the powerful stuff were common. Fumes from the tubs etched away the unique stain resistant coating on the TB bacillus over vacation. Someone stained it and like magic, the invisible became not only visible but understood. Robert Koch and Paul Erlichman became the fathers of modern microbiology. A similar thing happened with Flemming and penicillin. What is really amazing is the humble beginnings rapidly formalized into the science of antibiotics.
We discovered that microbes are constantly at war. Bacteria against bacteria, molds against molds and the whole microbial world is competing for resources, usually to the death. In fact, most of our antibiotics come from a microbe, like penicillium that produces a lethal toxin to most bacterial pathogens and harmless to us. We can go all the way to a human with antibodies to kill Ebola, fifty years ago we were using microscopic multicellular animals to study antibiotics and antibodies. Resistance to Pseudomonous and most super bugs isn't the little problem we believe it to be. Any microbiologist will tell you that we are at war with microbes. We are truly at risk of losing.
The good news is a dedication to rare infection treatment. We can run the genome of a pathogen and determine the ideal antibiotic or antibodies. In my opinion, we can kill a good drug by the power of suggestion, but as a scientist, I love my work and the dedication is beyond devotion.
The future is bright,
LL
