Aside from the day-to-day challenges of hospitalist medicine, practitioners who work in this environment are now often faced with growing public concern over hospital or healthcare-based infections. Unfortunately, as bacteria and other organisms evolve resistance to even the most powerful of our modern antibiotics and medicines, patients who are kept in the hospital for long periods of time may become susceptible to infections that cannot be cured. In the United States, patients are at highest risk of infection when they are kept in the intensive care unit. Some of the organisms that are known to pose a threat to patient health in hospital environments include methicillin-resistant S. aureus (MRSA), VRE, and ceftazidine-resistant Pseudomonas aeruginosa, among others.

Hospitalists are normally involved with diagnosing and treating a variety of conditions. In recent years, infection-control techniques have been developed to help combat the spread of infections by antibiotic resistant bacteria. One aspect of handling these types of infections is understanding how they begin and what risk factors a patient or the patient's environment may contain. For instance, inadequate hand washing or disinfection practices on the part of the hospital staff can be one contributing factor. Patients who stay in the hospital for a long time and who require the use of several types of permanent equipment (such as breathing tubes, catheters, etc.) are at increased risk for infection. Additionally, severely ill patients who are treated in an outpatient setting or at home may be risk if they use devices such as a central venous catheter. The reservoir (i.e. the place where the bacteria or organisms live before infecting a patient) can include healthcare workers themselves, tap water, soap dispensers, vials (in the hospital), mechanical ventilators, intravenous devices, and the like.

To make a patient sick, the microorganisms need to find their way from a reservoir and into their host in large enough numbers so that they can multiply (and ultimately, cause illness). For an infection to take hold, the dose needed depends in large part on how virulent (strong) the microorganism is, and how strong a patient's immune system happens to be at the time of infection. For example, some patients may become infected with resistant organisms and yet they may recover without any treatment at all. For others, however, the infection may cause death or prolonged illness.

Hospitalists, nurses, and other healthcare workers have the responsibility to treat patients for their conditions as well as protect them from unnecessary infection. To help reduce the chance of infection with antibiotic resistant microorganisms, healthcare workers can try to eliminate any reservoirs that might be present through cleaning, disinfection, and aggressive hand-washing campaigns. Substances that may pose a risk – such as tap water – can be cleaning using filtration systems, chlorine, and the like. If there are pathogens that survive cleaning measures on work surfaces in the hospital, more advanced cleaning techniques such as chemical treatment can be used when regular antiseptic cleaning methods are not effective enough. Using hand washing in addition to gloves, gowns, eye protection, and other "barrier" methods is also useful to help prevent healthcare workers from acting as reservoirs and then transmitting pathogens to vulnerable patients.

Unfortunately, bacteria can and will continue to evolve, and until newer antibiotic medicines are developed, prevention is a better option than treatment. Hospitalist medicine will continue to be influenced by the presence of these organisms for the foreseeable future.