Health-care associated infections are troublesome from many aspects, not only are they often more virulent or more resistant but also strike at the heart of health care: people go to the hospital to be cured, only to contract another potentially lethal disease.
As an example, the NIH Clinical Center in Bethesda, Maryland, suffered from an outbreak of carbapenem resistant Klebsiella pneumoniae in 2011. A patient carrying the bacterium was transferred there from a hospital in New York, and stayed for two days. In spite of every possible effort from the hospital staff, approximately three weeks after discharge of the first patient, another patient was infected with the strain. In all, 18 patients were affected, and 11 died – six of these deaths were directly attributable to the bacterium.
Another example is found in Anchorage, Alaska, also starting in 2011. Over a period of almost two years, a strain of Acinetobacter baumannii, unusual in being both highly resistant and highly virulent, infected 19 patients and contributed to the death of five of them. A. baumannii is an important cause of hospital-acquired pneumonia. While it is generally an opportunistic pathogen, its multidrug resistant varieties are often found in intensive care units where antibiotic usage is plentiful. Furthermore, it is capable of surviving e.g. on furniture for long periods, waiting for the opportune moment.
These two examples serve as reminders of the need for meticulous hospital hygiene and that our best efforts are sometimes just not sufficient.
Phages to the rescue?
Bacteriophages are viruses that only target bacteria: they inject their DNA into the host bacterium, replicate and finally kill the host bacterium, thereby releasing a multitude of newly assembled phages. Phages are easy and cheap to culture in any microbiology laboratory and can be selected to target specific bacterial strains effectively.
In a paper published in December 2016, researchers have tested a new possibility to manage the problem with health-care associated infections by using bacteriophages in decontamination of intensive care unit ICU rooms. The rooms were first cleaned according to the hospital standard procedure with sodium hypochlorite, followed by selective decontamination with phages.
The research group first cultured and validated a number of phages that were effective against carbapenem-resistant Acinetobacter baumannii (CRAB). When a patient with a CRAB-strain was identified at the ICU, the phages were tested against the strain. The most active phage was then used for decontamination of the room. The phages were spread over the ICU room with an ultrasonic fogger loaded with a phage suspension. The phages spread across the room with the fog, including hard to reach places, infecting and killing any bacteria of the targeted strain remaining after the standard cleaning.
The group compared the number of new cases of CRAB-infection, percentage of resistant Acinetobacter isolates and consumption of antibiotics used against CRAB during the study period with the year before the intervention. The occurrence of carbapenem resistant Pseudomonas aeruginosa was used to control that the noted changes were not due to general decrease of health-care associated infections in the ICU. Their analysis showed significant decrease in new CRAB-infections and antibiotic consumption, while the occurrence of Pseudomonas was unaffected. This suggests that the additional decontamination strategy has been successful in the trial.
Phages as therapy
In human medicine, bacteriophages have been used experimentally for decades to treat severe infections, mainly in the former Soviet Union and Eastern European countries. There have been some promising findings, sparking renewed interest in phage therapy in the wake of increasing antibiotic resistance. However, there are a number of obstacles in making phage therapy a standard treatment. Examples include:
- Phages cause an immune system reaction in the patient
- Lysis of the bacteria by the phage releases large quantities of endotoxin, which may cause fever or even shock in the patient
- Resistance to phages has also been described, and thus many therapeutic applications need to be “safeguarded” by using a cocktail or a sequence of different phages targeting the bacterium
- The need for constant renewal of phages in the cocktails due to potential development of resistance and strain specificity of the phages lead to regulatory problems, as each new individual cocktail need to be approved as a new drug.
Even though many of these hurdles could be overcome, phage therapy will probably not be able to replace antibiotics. However, it could potentially be a good complement to antibiotic therapy.
At face value, the study provides an interesting utilization of phages to limit the spread of health-care associated infections. Phages are easy and cheap to culture, even in resource-limited settings. An ultrasonic fogger is also not necessarily expensive, especially considering that one unit can serve a large department. And as human exposure to the fog is limited, it appears a safe option. However, one must bear in mind that this is one early-stage experience, the risk of resistance development needs to be continuously considered and that the success of a phage-based decontamination scheme is reliant on effective cleaning and decontamination routines as well as hospital hygiene.
Evan S. Snitkin, Adrian M. Zelazny, Pamela J. Thomas, et al. “Tracking a Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae with Whole-Genome Sequencing.” Science Translational Medicine 148 (2012), pp. 148ra116. DOI: 10.1126/scitranslmed.3004129
Yu-Huai Ho, Chun-Chieh Tseng, Lih-Shinn Wang, et al. ”Application of Bacteriophage-containing Aerosol against Nosocomial Transmission of Carbapenem-Resistant Acinetobacter baumannii in an Intensive Care Unit.” PLoS One 11(Dec 2016): e0168380 http://dx.doi.org/10.1371/journal.pone.0168380