The quest for vaccines for Clostridium difficile, Staphylococcus aureus, and other causes of healthcare-associated infections (HAIs) has not yet led to a breakthrough, but the promise of such a game-changing development makes for a dogged pursuit.

“There is primary prevention, where you are preventing disease in the person vaccinated, but the downstream effects are interesting to think about,” says Anthony Fiore, MD, MPH, MS, chief of epidemiologic research and innovations in the division of healthcare quality promotion at the Centers for Disease Control and Prevention (CDC).

For example, a patient who acquires MRSA typically is prescribed vancomycin, a last-line antibiotic that could be preserved if the patient had staph immunity via a vaccine.

Thus, vaccines against HAIs would immediately benefit antibiotic stewardship, which has taken on a sense of urgency with the rising tide of drug-resistant pathogens and the tendency of antibiotic use to select out C. diff in the patient gut.

“These are very challenging vaccines to make,” says Fiore.

“Many of these HAIs are caused by organisms for which we don’t really understand natural immunity. People can get C. diff infection multiple times. It’s not like measles or hepatitis A, where you get it once, it’s bad, but you never get it again because your immune system now ‘knows’ it.”

The problem is like the one encountered in the search for a universal influenza vaccine, where researchers are trying to recreate an immune response that the human body has not mounted in nature.

“For whatever reason, there are a lot of infections for which that is the case, whether that is because there are a lot of strain types or whether you just don’t ever develop good immunity,” he says.

“When you have a situation like that it is hard to understand how to make a vaccine, which is, of course, just trying to stimulate the patient immune system.”

As formidable as these barriers are, pharmaceutical companies continue to pursue HAI vaccines in part because the market for an effective one would be substantial.

“There are some pharmaceutical companies that have taken on this challenge, even in the face of some of the earlier staph vaccines and more recently a C. diff vaccine that have ultimately not worked — even though they looked good in the initial studies,” Fiore says.

The CDC is not directly involved in the clinical trials, but is staying abreast of the work for a possible breakthrough. Hurdles for safety on a large scale have been cleared, but ultimately vaccine efficacy has not been sustained.

Phase III trials for both a C. diff vaccine and an S. aureus vaccine were underway as this issue went to press.

“Fingers crossed,” Fiore says. “Sometimes we only understand in retrospect what the key component was that made a vaccine successful.”

If successful vaccine against HAIs could be developed, the initial indication would likely be for certain patient groups, he notes.

“The exception might be a C. diff vaccine if you tried to give it to everyone over 60 or something like an age-based recommendation,” he says.

“For a staph vaccine, you might end up giving it to people undergoing some sort of orthopedic surgery. Right now, the trial is in those getting spinal surgery. So, it might be that ultimately the indication is pretty narrow.”