Genetically competent care for those with chronic illnesses
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Alexandra Plavskin, MS, RN, is Clinical Instructor, Hunter College, New York, NY.
Genetics and Genomics of Pathogens: Fighting Infections with Genome-
Sequencing Technology
G enetics is “the study ofheredity” (World HealthOrganization [WHO], 2002, para. 1), while genomics is defined as “the study of genes and their functions, and related techniques” (para. 2). An expanded definition of genomics indicates “genetics scruti- nizes the functioning and composi- tion of the single gene whereas genomics addresses all genes and their interrelationships in order to identify their combined influence on the growth and development of the organism” (WHO, n.d., para. 3). Population genetics explores trait changes in a population and poten- tial contributing factors (Gillespie, 2010). Phylogenetics is the study of evolutionary relatedness between organisms (Wiley & Lieberman, 2011).
Background The study of human genetics and
genomics is imperative because the leading causes of mortality in the United States all have a genetic component, including cancer, heart disease, and diabetes (Calzone et al., 2010). However, the study of genet- ics and genomics of pathogens also can have substantial impact on clin- ical practice. The study of patho - gens can help identify sources of infection and manage outbreaks of health care-associated infections (HAIs), one of the top 10 causes of death in the United States (Calfee, 2012; Peleg & Hooper, 2010). Approximately 5% of persons ad - mitted to hospitals develop HAIs;
these patients have prolonged hos- pitalization as well as increased morbidity and mortality (Calfee, 2012). A retrospective 5-year med- ical record review of unexplained hospital deaths in one health care institution determined 31% may be due to HAIs (Calfee, 2012; Morgan, Lomotan, Agnes, McGrail, & Roghmann, 2010). HAIs are also a tremendous financial burden to health care institutions. Scott (2009) estimated U.S. hospitals spend $28- $45 billion annually in direct med- ical costs for HAIs. These estimates do not include indirect costs, such as loss of productivity or associated costs incurred by patients or their family members (Calfee, 2012).
Despite awareness of antimicro- bial-resistant organisms and efforts to contain them, resistant strains are emerging and spreading. De - velopment of new antibiotics is not keeping pace with the spread of antimicrobial-resistant infection (ARI) (Kishony & Collins, 2014). Individuals who develop these in - fections are at risk for increased morbidity and mortality, including prolonged hospital stay, delayed
recovery, or recurrent infection (Neidell et al., 2012; Roberts et al., 2009). Methicillin-resistant Staph - ylococcus aureus alone causes more deaths annually in the United States (~19,000) than Parkinson’s disease, emphysema, homicide, and HIV/AIDS combined. In addition, the estimated annual cost of ARI to the U.S. health care system is $21- $34 billion (Infectious Diseases Society of America [IDSA], 2011). A number of factors may contribute to increased antimicrobial resist- ance: overprescription of antimicro- bial medications, overuse of empiric antimicrobial therapy, the majority of prescriptions for antimicrobial therapy being written by prescribers who are not infectious disease spe- cialists, use of antibiotics for self- limiting viral infections, and use of antibiotics in livestock feed (IDSA, 2011; Roberts et al., 2009). Strict adherence to guidelines for infec- tion control is a national priority to combat HAIs (Septimus et al., 2014). In addition, genomic analy- ses of bacteria can provide insight into sources of infection, character- istics of organisms, and how health
Alexandra Plavskin
Discussions of clinical genetics and genomics often focus on screen- ing for disease-causing genes in humans and the promise of target- ed therapies. Another important area of research is analysis of pathogen genomes. Genetics and genomics-based approaches, such as population genomics and phylogenetics, provide insight into mechanisms of resistance, sources of infections, and pathogen transmission routes.
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care personnel can combat the spread of infections (Köser et al., 2012; Snitkin et al., 2012).
Genetics and Genomics of Pathogens
Several tools help researchers study genetics and genomics of pathogens. Whole genome sequen - cing (WGS) determines the entire sequence of an organism’s DNA. WGS of populations of bacteria allows researchers to study patterns of antibiotic resistance and patho gen transmission (Köser et al., 2012). Using population genetic approach- es, researchers can identify these pat- terns in large-scale studies of resist- ance following antibiotic adminis- tration across multiple pa tient cohorts. Alternatively, by construct- ing transmission maps, they can use genetic patterns in an infectious out- break to track patho gen transmis- sion in one health care institution. The contribution of genetics and genomics to the understanding of broad-scale spread of infections and individual patient-to-patient trans- mission is discussed. Possible influ- ence of population genetics and use of transmission maps on nursing practice also are discussed.
Population Genetics of Antibiotic Resistance
Population genetics studies found clarithromycin-resistant commensal bacteria persist in gastrointestinal (GI) flora years after completion of antibiotic therapy (Andersson & Hughes, 2010; Sjölund, Wreiber, Andersson, Blaser, & Engstrand, 2003). Commensal bacteria live in the GI system without causing adverse symptoms for the human host. Another study revealed amoxi cillin-resistant bacteria persist in oral cavities of children who have not taken amoxicillin in the past 3 months; some of those bacte- rial isolates were also resistant to erythromycin, penicillin, and tetra- cycline (Ready et al., 2004; Sommer & Dantas, 2011). These studies indi- cated antibiotic resistance can occur even if patients complete the entire antibiotic course and take the med- ication as directed. Pathogens can
also share virulence or resistance to antibiotics through transfer of genetic material between organisms (lateral gene transfer) (Harrison & Brockhurst, 2012; Smillie et al., 2011). Population genetics allows researchers and clinicians to identify patterns of prevalence and inci- dence in patho gens. Examples of these patterns include obtaining and harboring antibiotic-resistant bacteria months to years after taking antibiotics as prescribed, as well as bacterial ability to be resistant to several other antibiotics (Kritsotakis, Tsioutis, Roumbelaki, Christidou, & Gikas, 2011; Ready et al., 2004). Thus, previous antibiotic use may make patients more susceptible to antibiotic resistance against not only the prescribed antibiotic, but also other antibiotics. Nurses should include previous antibiotic use in the patient’s medication history. They also should monitor patients continuously for signs and symp- toms of infection, as previous antibi- otic use may influence effectiveness of other antibiotics.
Transmission Maps Another important application
of genome-sequencing technology is the use of transmission maps. Transmission maps attempt to iden- tify how infectious agents spread by documenting the pathogen’s gen - omic information, infected patients and their location, and/or any shared equipment. An outbreak of carbapenem-resistant Klebsiella pneumoniae in a National Institutes of Health Clinical Center promoted the use of whole genome bacterial sequencing and an algorithm to reconstruct the transmission of the infection (Snitkin et al., 2012). Researchers began by collecting iso- lates from multiple sites on the body of the patient initially identi- fied with the infection (index patient). They collected isolates from the groin, urine, and throat by using bronchoalveolar lavage. Cul - tures were collected from several locations because bacteria continu- ously evolve even when occupying one host. Therefore, bacteria in one anatomical region may differ genet- ically from bacteria in another loca-
tion. Researchers then collected samples from other patients and sequenced the bacterial genomes. The sequencing information was used to determine the evolutionary history of bacterial mutations, and was combined with epidemiologic information to construct a trans- mission map.
Phylogenetics, the study of evolu- tionary relatedness between organ - isms, is important when analyzing pathogen transmission because even small changes in genetic sequence provide a great deal of information (Sleator, 2013). Changes in genetic code, regardless of their effect on the organism, act as markers and can be used by researchers to trace the line- age of a pathogen. This process allows researchers to understand the spread of infections (see Figure 1). Identifying the gene sequence (via whole genome sequencing) then cre- ating a transmission map of the pathogen’s location and genetic changes can help researchers deter- mine who contracted the infection first and possibly where he or she contracted it (see Figure 2).
Genetic information can be used to identify unexpected modes of transmission when epidemiologic data are lacking, and can be used during outbreaks to guide infection control strategies. In the sample hypothetical transmission map in Figure 2, patient 1 was most likely the source of infection for patients 2 and 3. This conclusion is drawn from analysis of genetic mutations seen in Figure 1. This information would not be available solely from epidemiologic data. Figure 3 demon - strates patients 2 and 3 were in the Emergency Department (ED) simul- taneously. They may have shared equipment or were seen by the same health care providers, both possible sources for the spread of infection. Conversely, patients 1 and 3 were not on the same unit during their hospital stay, but genetic analysis indicated patient 3 was infected with a strain of bacte- ria from patient 1. This indicates a source of infection (equipment, staff person, or other patient) has yet to be identified and may contin- ue to spread the infection. Supple -
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menting the epidemiologic data with genomic analyses allows researchers to identify possible routes and sources of infections more effectively. Snitkin and col- leagues (2012) also described how transmission maps can help identi- fy the spread of infections.
For example, whole genome se - quencing of a ventilator culture identified K. pneumoniae bacteria on a ventilator that was cleaned twice with a quaternary ammonia solu- tion and once with bleach. Despite being cleaned three times, this ven- tilator was the source of K. pneumo- niae infection for a patient in the intensive care setting (Snitkin et al., 2012). However, whole genome sequencing and phylogenetic analy - sis demonstrated bacteria from the ventilator were related closely to those isolated in another infected patient. Analysis of the timing of infection occurrence and bacterial genome revealed the ventilator was the source of the infection, even though it was cleaned three times prior to additional use. Despite knowledge about the source of infection, many questions remain. The infection may have resulted from incorrect technique in clean- ing the ventilator, bacterial resist- ance to some cleaning agents, or a combination of both influences. Nurses and nurse researchers can play a vital role in gathering addi- tional information, and educating health care staff and patients about pathogen spread and prevention strategies.
Implications for Nursing Practice
Nurses are instrumental in stop- ping the spread of infections by testing new hospital protocols or encouraging use of existing infec- tion control practices. An impor- tant application is testing new hos- pital protocols for use of surveil- lance cultures. Protocols can be adapted to incorporate use of trans- mission maps and population genet- ics of bacteria. For example, during institutional outbreaks, health care leaders can consider unique charac- teristics of the causative agent (e.g.,
Genetics and Genomics of Pathogens: Fighting Infections with Genome-Sequencing Technology
FIGURE 1. Genetic Mutations
T A C G C
G C C G C
G C A G C
G C C C C
G C A G A
Ancestor
Patient 1
Patient 2
Patient 3
Patient 4
Patient 1 Strain: A T T C C G G Patient 2 Strain: A T TA C G G
Mutations in bacteria isolated from four patients and the ancestral (original) strain. Hypothetical data are used to demonstrate how genomic analysis can be used to derive the order of infection. Shaded squares represent new mutations relative to the ancestral strain. For example, bacteria cultured from patient 1 have two new muta- tions relative to the ancestral strain (column 1 the mutation was T → G; column 2 the mutation was A →C). Bacteria cultured from patient 2 have one new mutation relative to patient 1 (column 3). Bacteria cultured from patient 4 have one new mutation rel- ative to patient 2 (column 5). Bacteria cultured from patient 3 also have one new mutation relative to patient 1, but it is in a different location than the mutation in patient 2 (column 4); this indicates the mutation was most likely derived from patient 1, not patients 2 or 4.
FIGURE 2. Transmission Map
Transmission map constructed from hypothetical data in Figure 1. Bacteria cultured from patient 1 were closest to the ancestral DNA, with the lowest number of new mutations. Bacteria cultured from patients 2 and 4 are related mutations, while bac- teria cultured from patient 3 are an independent lineage. Genomic analysis also indi- cates bacteria from patient 2 most likely infected patient 4, deduced from the number of new mutations. Due to a variable incubation period, the time between contracting the infection and diagnosis may vary.
Ancestor Patient 1
Patient 3
Patient 2 Patient 4
Time when infection was contracted
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its likelihood to be transmitted by asymptomatic carriers, ability to form biofilms, or antimicrobial re - sistance) (Mah, 2012). Many of these characteristics can be determined quickly by whole genome sequenc- ing of pathogens. Culturing isolates through large-scale surveillance can identify pathogens; cultures should be obtained from patients, health- care staff, and equipment by nurses and hospital epidemiology staff (Snitkin et al., 2012). Applications of genetics and genomics can also be used to strengthen existing infection control practices.
Information provided by genetic testing of bacteria can guide educa- tional interventions for patients, family members, and health care staff. Nurses play an important role in patient and family education. Sequencing of bacterial genomes provides insight into how an infec- tion is being transmitted through a healthcare institution, including the likely source of infection, order of subsequent infections, and strains of bacteria infecting individ- ual patients (Snitkin et al., 2012). Nurses can use this information to educate patients and family mem- bers about ways to prevent infec- tion, such as correct handwashing techniques and the differences among air, droplet, and contact pre- cautions. In addition, nurses can provide education about possible asymptomatic colonization, the incubation period, and signs and symptoms of infection. Nurses can champion quality improvement initiatives to educate health care staff about a particular strain of infection, method of spread and strategies to prevent its spread, and where to obtain additional informa- tion. Healthcare leaders can review equipment and room cleaning pro- cedures with environmental servic- es staff, unlicensed assistive person- nel, and nurses to reinforce the importance of comprehensive de - contamination. They also can test available antimicrobial agents for effectiveness against a causative organism.
Clinical applications of genetics and genomics are also a tremen- dous opportunity for interprofes-
sional collaboration (Calzone, Jenkins, Prows, & Masny, 2011). Figure 3 demonstrates how epi- demiologic data alone may be insufficient to analyze and manage infection outbreaks. In that exam- ple, patients 2 and 3 were simulta- neously present in the ED; however, they did not contract the infection from each other. Nurses, epidemiol- ogists, physicians, geneticists, and other healthcare professionals must work together to understand and combat the spread of pathogens. The author recommends this inter- professional approach include the following: (a) patient, family, and health care staff education; (b) coor- dinated effort to collect and se - quence surveillance cultures; (c) vigilant use of isolation; (d) identifi-
cation of at-risk patients; (e) identi- fication of signs/symptoms of infec- tion; (f) determination of appropri- ate treatment plans; (g) administra- tion of treatment and supportive patient care; and (h) continuous vigilant patient assessment. Pop - ulation genetics and whole genome sequencing of bacteria are at the cutting edge of biology and health care, and tremendous opportunities are available for clinicians and researchers to collaborate to im - prove patient outcomes.
Knowledge about genetics and genomics continues to expand rap- idly. In response to this, nurse lead- ers from clinical, academic, and research settings worked collabora- tively to identify essential genetic and genomic competencies and
FIGURE 3. Patient Location
This diagram demonstrates how whole genome sequencing and the use of transmis- sion maps can provide information that is not available through epidemiologic analy- sis alone. This figure uses the same hypothetical data presented in Figures 1 and 2. Patients 2 and 3 were in the emergency department and were diagnosed with the infection. However, genomic analysis (see Figure 1) demonstrates patients 2 and 3 do not have the same ancestral strain of the infection. They were unlikely to get it from each other, although they were in the same location. However, patient 3 most likely contracted the infection from patient 1 although they were not in the same loca- tion during their hospital stay. This may indicate another infection source has yet to be identified (equipment, staff, or patient) and infection may continue to spread.
Intensive Care Unit
Emergency Department
Legend
Patient 1 Patient 2 Patient 3
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outcome indicators for nurses in all clinical specialties, roles, and prac- tice settings (Calzone et al., 2011; Jenkins & Calzone, 2007). Human genetics and genomics provide a number of important clinical tools, such as analysis of known gene vari- ants (e.g., BRCA 1, BRCA 2, APC, and BLMash) and use of pharmaco - genomics to decrease adverse med- ication events (e.g., warfarin dos- ing) (Kamatani et al., 2013; Raskin et al., 2011; Relling & Klein, 2011; Roy, Chun, & Powell, 2011). Under - standing pathogen genetics and genomics is also important to decrease the spread of infection and promote patient safety. Essential genetic and genomic competencies for nurses include interprofessional collaboration, patient advocacy, ability to interpret genetics and genomics information or services for patients, identification of pa - tients who may benefit from genet- ics and genomics information or services, and evaluation of the impact and effectiveness of genetics and genomics strategies on patient outcomes (Calzone et al., 2011; Jenkins & Calzone, 2007). Under - standing gene tics and genomics of patho gens will help nurses work
collaboratively with other health care professionals to decrease trans- mission of pathogens, educate patients and families, and promote improved patient outcomes.
Future Research Use of transmission maps and
population genetics provides a clin- ically relevant way to apply genetics and genomics to health care prac- tice (Rostved et al., 2013; Snitkin et al., 2012). Currently, they can be used to identify infection sources and methods of pathogen transmis- sion. Future research can address pathogen behavior in different patient populations and clinical environments. Research about how pathogens respond to treatments and develop resistance can be used to anticipate the formation of resist- ance, promote use of effective tar- geted therapies, and develop new therapies. Being able to obtain data about sources of infection, method of transmission, the path of the infection, and bacterial evolution in different environments can im - prove management of infectious disease in health care institutions.
Conclusion Existing infection protocol prac-
tices such as hand hygiene are the mainstay of infection control. How - ever, application of genetics and genomics, such as whole genome sequencing of pathogens, creation of transmission maps, and population genetics, can help researchers and health care personnel identify sources of infection and study how in fections spread. Col laborative efforts and incorporation of genetics and genomics can help the health care team fight multidrug- resistant pathogens and promote patient safety.
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Genetics and Genomics of Pathogens: Fighting Infections with Genome-Sequencing Technology
Instructions For Continuing Nursing Education Contact Hours
Genetics and Genomics of Pathogens: Fighting Infections with Genome-Sequencing Technology
Deadline for Submission: April 30, 2018 MSN J1606
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