REVIEW
Special considerations of antibiotic prescription in the geriatric population C. L. Beckett1, S. Harbarth2 and B. Huttner2 1) Infectious Diseases Department, Eastern Health, Victoria, Australia and 2) Infection Control Programme and Faculty of Medicine, Geneva, Switzerland
Abstract Infectious diseases pose a major challenge in the elderly for two reasons: on the one hand the susceptibility to infection increases with age and when infections occur they often present atypically—on the other hand diagnostic uncertainty is much more pronounced in the geriatric population. Reconciling the opposing aspects of optimizing patient outcomes while avoiding antibiotic overuse requires significant expertise that can be provided by an infectious diseases consultant. In addition, geriatric facilities are reservoirs for multidrug-resistant organisms and other nosocomial pathogens, and infectious diseases consultants also play a vital role in assuring appropriate infection control measures. In this review we outline the challenges of diagnosis and management of infectious diseases in the elderly, and discuss the importance of appropriate antibiotic use in the elderly in order to demonstrate the value of the infectious diseases consultant in this special setting. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Keywords: Antibiotic stewardship, antimicrobials, elderly, geriatrics, infectious diseases, prudent antibiotic use Original Submission: 7 August 2014; Accepted: 29 August 2014 Article published online: XXX
Corresponding author: B. Huttner, Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland E-mail: [email protected]
The aging population Over half of all deaths in many countries now occur in hospitals, even without taking into account deaths occurring in residential aged care institutions [1]. The vast majority of inhospital deaths occur among the elderly and the very old. In the USA for example, in 2010 75% of inpatients who died in a hospital were aged 65 years and over and 27% were aged 85 years and over [2]. Infections, such as pneumonia, often directly contribute to the mortality in these patients, as suggested by the term ‘end-of-life pneumonia’ [3]. This poses challenges with regard to the use of ‘end-of-life’ antibiotics, which may lower suffering but also may exacerbate selection pressure for antimicrobial resistance [4–6]. The prevention, diagnosis and management of infections in geriatric patients, requires the expertise of infectious diseases (ID) consultants with an interest
in this area of medicine. In addition, ID consultants also have a major role in promoting the judicious use of antibiotics in this population, since it is also particularly vulnerable to the deleterious effects of inappropriate antibiotic use, such as adverse drug reactions, antimicrobial resistance and Clostridium difficile infection [7].
The high risk of infectious diseases in the elderly While aging is a normal process, and not in itself a disease, agerelated physiological changes place the elderly at high risk for infectious diseases [8]. These diseases are therefore a leading cause of hospital admission and cause of death in this patient population [9]. Susceptibility to infectious diseases in the elderly is increased by a combination of factors, including immune senescence (such as changes in B-cell and T-cell function, innate immune responses and effector functions), as well as altered skin and mucosal barrier function, degenerative changes in bone and cartilage and reduction in respiratory capacity [9–11]. Urinary catheters are often used in geriatrics facilities and
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prevalence estimates of these devices range between 6 and 40%, depending on the population studied [12]. Approximately 3–7% of nursing home residents with an indwelling urinary catheter will acquire a urinary tract infection with each day that the catheter remains in place. The changes in immune system function in the elderly lead to reduced responsiveness to vaccination, and increased susceptibility to systemic infection by specific pathogens such as Listeria monocytogenes. Additionally, reactivation of latent infection such as Mycobacterium tuberculosis and varicella zoster virus is also more common [13–15]. Common co-morbidities found in the aging population also contribute to an increased risk of infection, such as pulmonary diseases increasing the risk of pneumonia, and the frequent presence of foreign material, such as joint prostheses, pacemakers or artificial cardiac valves, enhancing risk of prosthetic device infection [16]. Elderly patients in institutions, such as nursing homes or geriatric hospitals, pose a particular challenge. Not only does this group of patients tend to have more pronounced impairment of defences against infection, and a large number of comorbidities, but common activities (e.g. common meals) combined with suboptimal hygiene (e.g. due to a high proportion of patients with dementia) promote rapid dissemination of respiratory and gastrointestinal viruses (e.g. influenza virus and norovirus) and multidrug-resistant organisms (MDROs) [16,17]. Several studies have shown that age remains an important risk factor of carriage of MDROs, independent of other determinants [18]. Furthermore, geriatric hospitals may have a higher prevalence of nosocomial infections compared with acute-care settings, even after adjustment for case-mix [19]. The outcome from infection is often worse in elderly populations. For example, mortality related to Staphylococcus aureus bacteraemia has been extensively studied, and shows a significant increase in mortality in the later decades of life [20,21]. Prognosis for severe infections, particularly in geriatric patients more than 80 years of age, is clearly linked to functional status [22].
Unusual presentation of infectious diseases in the elderly Common infections such as urinary tract infections, lower respiratory tract infections and skin and soft tissue infections, are frequent in the elderly [16]. Unfortunately, however, the diagnosis of infection in the elderly is not always straightforward and obvious. Symptoms and signs of infection in the elderly may not include the typical features such as fever and chills that clinicians usually rely on to make a clinical diagnosis of infection
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[23,24]. This is because of altered physiological responses to the infecting pathogen in this patient group, and age-related changes in temperature regulation [25]. Older subjects have a lower body temperature than that of younger people and their tolerance of thermal extremes is more limited. Instead, symptoms may mimic normal signs of aging or a concomitant disease, or symptoms may be non-specific such as when elderly patients with pneumonia present solely with confusion. Conversely, patients may have fever without apparent infections complicating the decision to administer antibiotics to elderly patients [24]. In addition, accurate history taking is often complicated by cognitive impairment, the physical examination is often hampered by lack of cooperation and the positive predictive value of many diagnostic tests is lower than in the other populations (e.g. chest X-rays or urinary cultures). Acute confusion or disturbance of consciousness is one of the common atypical (relative to non-elderly) primary manifestations of infection in geriatric patients [9]. In an analysis of 73 consecutive acute admissions of patients older than 70 with impaired consciousness, the proportion where a presumed infection was the triggering cause was 34.3% [9]. Other nonspecific manifestations of infection in the elderly can include acute deterioration of mobility, and subtle disturbances of circulatory regulation (hypotension and lactic acidosis without overt toxaemia or tachycardia) [9]. Altered cognitive states such as dementia or acute confusion often hamper the ability of the clinician to obtain important details regarding relevant symptoms or risk factors for infection, further complicating the process of accurate clinical diagnosis in this patient group [26]. Laboratory markers of infection may not show responses found typically in younger patients. Inflammatory markers are often initially not elevated or are minimally abnormal in the infected geriatric patient, further contributing to delays in diagnosis and therapy [27,28]. The presentation of urinary tract infections in the elderly may be atypical. Positive urinary cultures without active infection are very common in the elderly, reducing the positive predictive value of bacteriuria for diagnosing urinary tract infections and, in the absence of better performing diagnostic tests, making it difficult—if not impossible in certain cases—to differentiate between asymptomatic bacteriuria and active urinary tract infection [8,9]. The frequency of bacteraemia increases in elderly patients, and is one of the leading causes of morbidity and mortality in the geriatric population [29]. Fever, chills and shakes are less likely to be present; however, fever remains common in bacteraemic geriatric patients [30,31]. End-organ effects are reported to be more common in the elderly bacteraemic patients, with manifestations such as renal failure and respiratory compromise [31]. There does not appear to be a difference in
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the specificity or sensitivity of positive blood cultures with age, if the cultures are collected appropriately [32]. However, given the potential for non-specific presentations of infections in the elderly, the key challenge is collecting cultures in the appropriate patient group [8]. In general there should be a low threshold for obtaining blood cultures in older patients, even in the absence of fever, in selected patients with changes in the functional status (e.g. new confusion) [8]. Unusual microorganisms may be more prevalent in the very aged population, as demonstrated in a retrospective, multicentre cohort study that revealed age >90 years as an independent risk factor for Pseudomonas aeruginosa bacteraemia on hospital admission [33]. As described above, the outcome from bacteraemia is usually worse for elderly patients with higher rates of mortality. Lower respiratory tract infections and pneumonia are leading causes of morbidity and mortality in older patients, resulting in almost half of all infectious disease-related hospitalizations and deaths [34–36]. The diagnosis of pneumonia may not be obvious in the elderly. This is especially true for nosocomial pneumonia. Classical presentations of pneumonia are often absent in the elderly with less chest pain, fever, chills, cough or expectoration [8,9]. The standard investigation for pneumonia diagnosis, chest radiography, is difficult to interpret because of non-specific radiological findings in elderly patients and suboptimal quality of radiographs [37]. In practical terms this means that it is hard, if not impossible, to exclude pneumonia based on a chest radiograph, which contributes to significant diagnostic uncertainty and can result in incorrect or unnecessary therapy. Additionally there is often difficulty obtaining adequate sputum samples for culture and consequently no pathogen is identified in most older patients with pneumonia [24,38–40]. With increasing age prosthetic valve endocarditis, which is often more difficult to treat, becomes more common [41,42]. Elderly patients are less likely to present with peripheral stigmata of endocarditis, such as splenomegaly and Osler’s nodes [8]. While the spectrum of offending pathogens remains similar, the need for transoesophageal echocardiogram to confirm the diagnosis of endocarditis may be increased in elderly patients [41]. Decisions regarding the appropriate investigation and management of elderly patients with possible bacterial endocarditis are frequently difficult, not only because of the perceived invasive nature of the testing that is required, but because of the prolonged duration of therapy necessary to cure the infection. Overall, this uncertainty puts physicians treating the elderly in a difficult situation when having to decide whether to start antibiotics. On the one hand, several factors favour a ‘low threshold’ to antibiotic therapy: infections are frequent in this population, have a higher morbidity and mortality than in
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younger adults and may present atypically. On the other hand, several factors would favour a ‘high threshold’ to start antibiotic therapy: numerous other factors may contribute to alterations in the physical status and fever in this population and diagnostic tests are rarely useful to exclude infections. This population is also particularly vulnerable to the deleterious effect of unnecessary antibiotic use. The timely and accurate assessment of infections in the elderly patient group therefore requires expertise in this area, with an understanding of the altered manifestations of infection in this patient group [8]. On the other hand, it is just as important that the ID consultant supports the treating geriatricians in decisions not to treat a patient with antibiotics, when an infection is not certain and ‘watchful waiting’ may be justified.
Management of infectious diseases in geriatrics is a challenge The management of infectious diseases in geriatric patients in relation to their multiple co-morbidities, poly-pharmacotherapy, impending disabilities and functional impairments is a unique challenge [9]. In addition, decisions about appropriate duration of therapy, such as the need for curative therapy versus long-term suppression, require the expertise of physicians with knowledge and expertise in this area. With regard to many day-to-day decisions about the management of infectious diseases in the elderly, we essentially move to an ‘evidence-free’ area that is largely based on expert opinion. While the evidence base for most infectious disease recommendations is already weak, this is certainly even worse for the elderly, who are often underrepresented in clinical trials of new therapeutic or preventive interventions [43]. All too often clinicians are confronted with a geriatric patient with fever, elevated inflammatory markers or merely confusion, with an abnormal urine status and a questionable infiltrate on a chest X ray. More often than not, these non-specific findings lead the physician to commence antibiotic therapy often with broad-spectrum drugs. It is in these instances that the geriatric ID consultant can provide valuable input.
Antibiotic therapy in the elderly Early administration of appropriate antimicrobials has been postulated as a key strategy in the survival of patients with very severe infections requiring intensive care unit admission [44,45]. However, it is unclear how far these data can be extrapolated to other patient groups. Rapid, indiscriminate
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TABLE 1. Selected challenges and the role of infectious diseases consultants in managing infectious diseases in geriatrics Challenge
Role of ID consultant in meeting challenge
Atypical presentations of infectious diseases
Balance risk of not treating an infectious disease with risk associated with unnecessary antibiotic use on the individual and the ecological level High risk of nursing home/geriatric ward Ensure appropriate vaccination of outbreaks of viral infections residents (e.g. influenza) Design strategies to prevent spread within nursing homes Respond to and manage outbreaks of infection rapidly Colonization and infection with Implement appropriate infection control antibiotic-resistant bacterial pathogens strategies to: in geriatric wards and nursing homes Screen for drug resistant pathogens Prevent spread within the nursing home Prevent spread to acute-care hospitals Develop local empiric treatment guidelines for nursing home patients presenting with severe infections Altered antibiotic metabolism and drug Careful consideration of drug therapies. interactions Liaison with clinical pharmacist.
administration of broad-spectrum antibiotic therapy favours antibiotic resistance [46]. There are significant risks and possible adverse consequences of inappropriate antibiotic therapy in the elderly, including risks of drug interactions, side effects related to age or disease-related changes in metabolisms, and risks associated with MDROs and Clostridium difficile.
Drug-resistant bacterial infections and the elderly Outbreaks of infection with MDROs are frequently reported from long-term care facilities, and high rates of colonization with resistant pathogens are also reported, even among community-dwelling elderly [47–51]. A low functional status is a common risk factor both for both extended-spectrum β-lactamase-producing Enterobacteriaceae and for methicillinresistant S. aureus colonization, and it highlights the need to reinforce infection control measures and promote the judicious use of antibiotics [17,18,52]. Of special concern is the recent worldwide emergence of carbapenem-resistant Enterobacteriaceae. Long-term care and geriatric institutions seem to be especially concerned by carbapenem-resistant Enterobacteriaceae outbreaks and may serve as a reservoir for spread to the acute-care setting [53]. Antibiotic exposure increases the risk of both acquiring and transmitting most MDROs, but the mechanisms are complex [54–57]. An increasingly recognized deleterious effect of antibiotic exposure is its effect on the
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patient’s microbiome [58]. The most striking example is C. difficile infection, which is rare in the absence of previous antibiotic exposure impairing the ‘colonization resistance’ provided by the healthy gut microbiota. It is estimated that in the USA alone 250 000 illnesses and 14 000 deaths each year are due to C. difficile infection [59]. These facts highlight the importance of judicious antibiotic use in geriatric patients. Here the ID consultant with expertise in decision-making in situations of diagnostic uncertainty and protocol generation make an important contribution. The authors would argue that in the geriatric setting the role of the ID physician as the steward of not only antibiotics, but also the patients’ microbiome, is even more important than in other specialties.
Value of the infectious diseases consultant In the previous sections we have already alluded to the role of the ID consultant in geriatrics. Table 1 summarizes key challenges in geriatric infectious diseases and the role of the ID consultant in addressing these. While based on the arguments outlined above the value of the ID consultant may seem obvious, there is a paucity of data regarding the value of ID consultation in general. A major limitation of the existing studies is that they are almost exclusively conducted by ID specialists, who clearly have an interest in demonstrating their own usefulness and this may impact the credibility of these findings for other physicians. Recent studies have examined the involvement of ID consultants in some inpatient specialty areas, including orthopaedic surgery, critical care and oncology [60–63]. These studies suggest, not surprisingly, that involvement of ID consultants often results in modification of the antibiotic treatment regimen and may also decrease overall antibiotic use, costs and complications [60]. The ID consultant also has an important understanding of current local antimicrobial resistance patterns, a factor that is critical in making correct empiric treatment decisions in geriatric patients where there is a high risk of resistance. In addition, ID consultants may be useful in the evaluation of unclear febrile syndromes [64]. Some studies also report that ID consultation and adherence to its recommendations results in improved outcomes in inpatient and outpatient settings. This is best documented for S. aureus bacteraemia, where ID consultation has been shown to decrease mortality, give better adherence to standard of care, decrease rate of relapse, and improve diagnosis of metastatic foci of infection or endocarditis [65–71]. A recent US study looking at claims data from over 270 000 hospitalized patients with one or more of 11 types of infections (e.g. bacteraemia, C. difficile infection, endocarditis etc.), determined that after risk adjustment, ID input was
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associated with better outcomes and lower cost of care. These benefits were greatest when ID specialist involvement started within the first 2 days of hospital admission [72]. In our experience the ID consultant has other important roles, especially when interacting with inexperienced physicians and junior house officers, to address practical issues such as the role of vascular access devices or urinary catheters as a focus of infection, the need for device removal, and the role of surgery in deep-seated infection. Geriatric units may not have significant input from hospital infection-control physicians. Given the high rates of drug-resistant pathogens and the risk of nosocomial outbreaks in these populations, ‘infection-control physician’ is another vital role that ID consultants can perform in the geriatric setting.
Conclusion As outlined above, the prevention, diagnosis and management of infectious diseases in geriatric patients poses significant and evolving challenges. While clinical studies have not yet been undertaken to measure the impact of ID consultants in geriatrics, ID consultants who work closely with geriatric units are well placed to optimize the diagnosis and management of infections within the unit, and to respond to evolving challenges in the prevention of infection, especially in a role as an infection control advisor and antibiotic steward.
Transparency Declaration The authors declare that they have no conflicts of interest.
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Special considerations of antibiotic prescription in the geriatric population C. L. Beckett1, S. Harbarth2 and B. Huttner2 1) Infectious Diseases Department, Eastern Health, Victoria, Australia and 2) Infection Control Programme and Faculty of Medicine, Geneva, Switzerland
Abstract Infectious diseases pose a major challenge in the elderly for two reasons: on the one hand the susceptibility to infection increases with age and when infections occur they often present atypically—on the other hand diagnostic uncertainty is much more pronounced in the geriatric population. Reconciling the opposing aspects of optimizing patient outcomes while avoiding antibiotic overuse requires significant expertise that can be provided by an infectious diseases consultant. In addition, geriatric facilities are reservoirs for multidrug-resistant organisms and other nosocomial pathogens, and infectious diseases consultants also play a vital role in assuring appropriate infection control measures. In this review we outline the challenges of diagnosis and management of infectious diseases in the elderly, and discuss the importance of appropriate antibiotic use in the elderly in order to demonstrate the value of the infectious diseases consultant in this special setting. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Keywords: Antibiotic stewardship, antimicrobials, elderly, geriatrics, infectious diseases, prudent antibiotic use Original Submission: 7 August 2014; Accepted: 29 August 2014 Article published online: XXX
Corresponding author: B. Huttner, Infection Control Programme, Geneva University Hospitals, Geneva, Switzerland E-mail: [email protected]
The aging population Over half of all deaths in many countries now occur in hospitals, even without taking into account deaths occurring in residential aged care institutions [1]. The vast majority of inhospital deaths occur among the elderly and the very old. In the USA for example, in 2010 75% of inpatients who died in a hospital were aged 65 years and over and 27% were aged 85 years and over [2]. Infections, such as pneumonia, often directly contribute to the mortality in these patients, as suggested by the term ‘end-of-life pneumonia’ [3]. This poses challenges with regard to the use of ‘end-of-life’ antibiotics, which may lower suffering but also may exacerbate selection pressure for antimicrobial resistance [4–6]. The prevention, diagnosis and management of infections in geriatric patients, requires the expertise of infectious diseases (ID) consultants with an interest
in this area of medicine. In addition, ID consultants also have a major role in promoting the judicious use of antibiotics in this population, since it is also particularly vulnerable to the deleterious effects of inappropriate antibiotic use, such as adverse drug reactions, antimicrobial resistance and Clostridium difficile infection [7].
The high risk of infectious diseases in the elderly While aging is a normal process, and not in itself a disease, agerelated physiological changes place the elderly at high risk for infectious diseases [8]. These diseases are therefore a leading cause of hospital admission and cause of death in this patient population [9]. Susceptibility to infectious diseases in the elderly is increased by a combination of factors, including immune senescence (such as changes in B-cell and T-cell function, innate immune responses and effector functions), as well as altered skin and mucosal barrier function, degenerative changes in bone and cartilage and reduction in respiratory capacity [9–11]. Urinary catheters are often used in geriatrics facilities and
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prevalence estimates of these devices range between 6 and 40%, depending on the population studied [12]. Approximately 3–7% of nursing home residents with an indwelling urinary catheter will acquire a urinary tract infection with each day that the catheter remains in place. The changes in immune system function in the elderly lead to reduced responsiveness to vaccination, and increased susceptibility to systemic infection by specific pathogens such as Listeria monocytogenes. Additionally, reactivation of latent infection such as Mycobacterium tuberculosis and varicella zoster virus is also more common [13–15]. Common co-morbidities found in the aging population also contribute to an increased risk of infection, such as pulmonary diseases increasing the risk of pneumonia, and the frequent presence of foreign material, such as joint prostheses, pacemakers or artificial cardiac valves, enhancing risk of prosthetic device infection [16]. Elderly patients in institutions, such as nursing homes or geriatric hospitals, pose a particular challenge. Not only does this group of patients tend to have more pronounced impairment of defences against infection, and a large number of comorbidities, but common activities (e.g. common meals) combined with suboptimal hygiene (e.g. due to a high proportion of patients with dementia) promote rapid dissemination of respiratory and gastrointestinal viruses (e.g. influenza virus and norovirus) and multidrug-resistant organisms (MDROs) [16,17]. Several studies have shown that age remains an important risk factor of carriage of MDROs, independent of other determinants [18]. Furthermore, geriatric hospitals may have a higher prevalence of nosocomial infections compared with acute-care settings, even after adjustment for case-mix [19]. The outcome from infection is often worse in elderly populations. For example, mortality related to Staphylococcus aureus bacteraemia has been extensively studied, and shows a significant increase in mortality in the later decades of life [20,21]. Prognosis for severe infections, particularly in geriatric patients more than 80 years of age, is clearly linked to functional status [22].
Unusual presentation of infectious diseases in the elderly Common infections such as urinary tract infections, lower respiratory tract infections and skin and soft tissue infections, are frequent in the elderly [16]. Unfortunately, however, the diagnosis of infection in the elderly is not always straightforward and obvious. Symptoms and signs of infection in the elderly may not include the typical features such as fever and chills that clinicians usually rely on to make a clinical diagnosis of infection
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[23,24]. This is because of altered physiological responses to the infecting pathogen in this patient group, and age-related changes in temperature regulation [25]. Older subjects have a lower body temperature than that of younger people and their tolerance of thermal extremes is more limited. Instead, symptoms may mimic normal signs of aging or a concomitant disease, or symptoms may be non-specific such as when elderly patients with pneumonia present solely with confusion. Conversely, patients may have fever without apparent infections complicating the decision to administer antibiotics to elderly patients [24]. In addition, accurate history taking is often complicated by cognitive impairment, the physical examination is often hampered by lack of cooperation and the positive predictive value of many diagnostic tests is lower than in the other populations (e.g. chest X-rays or urinary cultures). Acute confusion or disturbance of consciousness is one of the common atypical (relative to non-elderly) primary manifestations of infection in geriatric patients [9]. In an analysis of 73 consecutive acute admissions of patients older than 70 with impaired consciousness, the proportion where a presumed infection was the triggering cause was 34.3% [9]. Other nonspecific manifestations of infection in the elderly can include acute deterioration of mobility, and subtle disturbances of circulatory regulation (hypotension and lactic acidosis without overt toxaemia or tachycardia) [9]. Altered cognitive states such as dementia or acute confusion often hamper the ability of the clinician to obtain important details regarding relevant symptoms or risk factors for infection, further complicating the process of accurate clinical diagnosis in this patient group [26]. Laboratory markers of infection may not show responses found typically in younger patients. Inflammatory markers are often initially not elevated or are minimally abnormal in the infected geriatric patient, further contributing to delays in diagnosis and therapy [27,28]. The presentation of urinary tract infections in the elderly may be atypical. Positive urinary cultures without active infection are very common in the elderly, reducing the positive predictive value of bacteriuria for diagnosing urinary tract infections and, in the absence of better performing diagnostic tests, making it difficult—if not impossible in certain cases—to differentiate between asymptomatic bacteriuria and active urinary tract infection [8,9]. The frequency of bacteraemia increases in elderly patients, and is one of the leading causes of morbidity and mortality in the geriatric population [29]. Fever, chills and shakes are less likely to be present; however, fever remains common in bacteraemic geriatric patients [30,31]. End-organ effects are reported to be more common in the elderly bacteraemic patients, with manifestations such as renal failure and respiratory compromise [31]. There does not appear to be a difference in
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the specificity or sensitivity of positive blood cultures with age, if the cultures are collected appropriately [32]. However, given the potential for non-specific presentations of infections in the elderly, the key challenge is collecting cultures in the appropriate patient group [8]. In general there should be a low threshold for obtaining blood cultures in older patients, even in the absence of fever, in selected patients with changes in the functional status (e.g. new confusion) [8]. Unusual microorganisms may be more prevalent in the very aged population, as demonstrated in a retrospective, multicentre cohort study that revealed age >90 years as an independent risk factor for Pseudomonas aeruginosa bacteraemia on hospital admission [33]. As described above, the outcome from bacteraemia is usually worse for elderly patients with higher rates of mortality. Lower respiratory tract infections and pneumonia are leading causes of morbidity and mortality in older patients, resulting in almost half of all infectious disease-related hospitalizations and deaths [34–36]. The diagnosis of pneumonia may not be obvious in the elderly. This is especially true for nosocomial pneumonia. Classical presentations of pneumonia are often absent in the elderly with less chest pain, fever, chills, cough or expectoration [8,9]. The standard investigation for pneumonia diagnosis, chest radiography, is difficult to interpret because of non-specific radiological findings in elderly patients and suboptimal quality of radiographs [37]. In practical terms this means that it is hard, if not impossible, to exclude pneumonia based on a chest radiograph, which contributes to significant diagnostic uncertainty and can result in incorrect or unnecessary therapy. Additionally there is often difficulty obtaining adequate sputum samples for culture and consequently no pathogen is identified in most older patients with pneumonia [24,38–40]. With increasing age prosthetic valve endocarditis, which is often more difficult to treat, becomes more common [41,42]. Elderly patients are less likely to present with peripheral stigmata of endocarditis, such as splenomegaly and Osler’s nodes [8]. While the spectrum of offending pathogens remains similar, the need for transoesophageal echocardiogram to confirm the diagnosis of endocarditis may be increased in elderly patients [41]. Decisions regarding the appropriate investigation and management of elderly patients with possible bacterial endocarditis are frequently difficult, not only because of the perceived invasive nature of the testing that is required, but because of the prolonged duration of therapy necessary to cure the infection. Overall, this uncertainty puts physicians treating the elderly in a difficult situation when having to decide whether to start antibiotics. On the one hand, several factors favour a ‘low threshold’ to antibiotic therapy: infections are frequent in this population, have a higher morbidity and mortality than in
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younger adults and may present atypically. On the other hand, several factors would favour a ‘high threshold’ to start antibiotic therapy: numerous other factors may contribute to alterations in the physical status and fever in this population and diagnostic tests are rarely useful to exclude infections. This population is also particularly vulnerable to the deleterious effect of unnecessary antibiotic use. The timely and accurate assessment of infections in the elderly patient group therefore requires expertise in this area, with an understanding of the altered manifestations of infection in this patient group [8]. On the other hand, it is just as important that the ID consultant supports the treating geriatricians in decisions not to treat a patient with antibiotics, when an infection is not certain and ‘watchful waiting’ may be justified.
Management of infectious diseases in geriatrics is a challenge The management of infectious diseases in geriatric patients in relation to their multiple co-morbidities, poly-pharmacotherapy, impending disabilities and functional impairments is a unique challenge [9]. In addition, decisions about appropriate duration of therapy, such as the need for curative therapy versus long-term suppression, require the expertise of physicians with knowledge and expertise in this area. With regard to many day-to-day decisions about the management of infectious diseases in the elderly, we essentially move to an ‘evidence-free’ area that is largely based on expert opinion. While the evidence base for most infectious disease recommendations is already weak, this is certainly even worse for the elderly, who are often underrepresented in clinical trials of new therapeutic or preventive interventions [43]. All too often clinicians are confronted with a geriatric patient with fever, elevated inflammatory markers or merely confusion, with an abnormal urine status and a questionable infiltrate on a chest X ray. More often than not, these non-specific findings lead the physician to commence antibiotic therapy often with broad-spectrum drugs. It is in these instances that the geriatric ID consultant can provide valuable input.
Antibiotic therapy in the elderly Early administration of appropriate antimicrobials has been postulated as a key strategy in the survival of patients with very severe infections requiring intensive care unit admission [44,45]. However, it is unclear how far these data can be extrapolated to other patient groups. Rapid, indiscriminate
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TABLE 1. Selected challenges and the role of infectious diseases consultants in managing infectious diseases in geriatrics Challenge
Role of ID consultant in meeting challenge
Atypical presentations of infectious diseases
Balance risk of not treating an infectious disease with risk associated with unnecessary antibiotic use on the individual and the ecological level High risk of nursing home/geriatric ward Ensure appropriate vaccination of outbreaks of viral infections residents (e.g. influenza) Design strategies to prevent spread within nursing homes Respond to and manage outbreaks of infection rapidly Colonization and infection with Implement appropriate infection control antibiotic-resistant bacterial pathogens strategies to: in geriatric wards and nursing homes Screen for drug resistant pathogens Prevent spread within the nursing home Prevent spread to acute-care hospitals Develop local empiric treatment guidelines for nursing home patients presenting with severe infections Altered antibiotic metabolism and drug Careful consideration of drug therapies. interactions Liaison with clinical pharmacist.
administration of broad-spectrum antibiotic therapy favours antibiotic resistance [46]. There are significant risks and possible adverse consequences of inappropriate antibiotic therapy in the elderly, including risks of drug interactions, side effects related to age or disease-related changes in metabolisms, and risks associated with MDROs and Clostridium difficile.
Drug-resistant bacterial infections and the elderly Outbreaks of infection with MDROs are frequently reported from long-term care facilities, and high rates of colonization with resistant pathogens are also reported, even among community-dwelling elderly [47–51]. A low functional status is a common risk factor both for both extended-spectrum β-lactamase-producing Enterobacteriaceae and for methicillinresistant S. aureus colonization, and it highlights the need to reinforce infection control measures and promote the judicious use of antibiotics [17,18,52]. Of special concern is the recent worldwide emergence of carbapenem-resistant Enterobacteriaceae. Long-term care and geriatric institutions seem to be especially concerned by carbapenem-resistant Enterobacteriaceae outbreaks and may serve as a reservoir for spread to the acute-care setting [53]. Antibiotic exposure increases the risk of both acquiring and transmitting most MDROs, but the mechanisms are complex [54–57]. An increasingly recognized deleterious effect of antibiotic exposure is its effect on the
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patient’s microbiome [58]. The most striking example is C. difficile infection, which is rare in the absence of previous antibiotic exposure impairing the ‘colonization resistance’ provided by the healthy gut microbiota. It is estimated that in the USA alone 250 000 illnesses and 14 000 deaths each year are due to C. difficile infection [59]. These facts highlight the importance of judicious antibiotic use in geriatric patients. Here the ID consultant with expertise in decision-making in situations of diagnostic uncertainty and protocol generation make an important contribution. The authors would argue that in the geriatric setting the role of the ID physician as the steward of not only antibiotics, but also the patients’ microbiome, is even more important than in other specialties.
Value of the infectious diseases consultant In the previous sections we have already alluded to the role of the ID consultant in geriatrics. Table 1 summarizes key challenges in geriatric infectious diseases and the role of the ID consultant in addressing these. While based on the arguments outlined above the value of the ID consultant may seem obvious, there is a paucity of data regarding the value of ID consultation in general. A major limitation of the existing studies is that they are almost exclusively conducted by ID specialists, who clearly have an interest in demonstrating their own usefulness and this may impact the credibility of these findings for other physicians. Recent studies have examined the involvement of ID consultants in some inpatient specialty areas, including orthopaedic surgery, critical care and oncology [60–63]. These studies suggest, not surprisingly, that involvement of ID consultants often results in modification of the antibiotic treatment regimen and may also decrease overall antibiotic use, costs and complications [60]. The ID consultant also has an important understanding of current local antimicrobial resistance patterns, a factor that is critical in making correct empiric treatment decisions in geriatric patients where there is a high risk of resistance. In addition, ID consultants may be useful in the evaluation of unclear febrile syndromes [64]. Some studies also report that ID consultation and adherence to its recommendations results in improved outcomes in inpatient and outpatient settings. This is best documented for S. aureus bacteraemia, where ID consultation has been shown to decrease mortality, give better adherence to standard of care, decrease rate of relapse, and improve diagnosis of metastatic foci of infection or endocarditis [65–71]. A recent US study looking at claims data from over 270 000 hospitalized patients with one or more of 11 types of infections (e.g. bacteraemia, C. difficile infection, endocarditis etc.), determined that after risk adjustment, ID input was
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associated with better outcomes and lower cost of care. These benefits were greatest when ID specialist involvement started within the first 2 days of hospital admission [72]. In our experience the ID consultant has other important roles, especially when interacting with inexperienced physicians and junior house officers, to address practical issues such as the role of vascular access devices or urinary catheters as a focus of infection, the need for device removal, and the role of surgery in deep-seated infection. Geriatric units may not have significant input from hospital infection-control physicians. Given the high rates of drug-resistant pathogens and the risk of nosocomial outbreaks in these populations, ‘infection-control physician’ is another vital role that ID consultants can perform in the geriatric setting.
Conclusion As outlined above, the prevention, diagnosis and management of infectious diseases in geriatric patients poses significant and evolving challenges. While clinical studies have not yet been undertaken to measure the impact of ID consultants in geriatrics, ID consultants who work closely with geriatric units are well placed to optimize the diagnosis and management of infections within the unit, and to respond to evolving challenges in the prevention of infection, especially in a role as an infection control advisor and antibiotic steward.
Transparency Declaration The authors declare that they have no conflicts of interest.
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Please cite this article in press as: Beckett CL, et al., Special considerations of antibiotic prescription in the geriatric population, Clinical Microbiology and Infection (2014), http:// dx.doi.org/10.1016/j.cmi.2014.08.018
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Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, xxx 1–7
Please cite this article in press as: Beckett CL, et al., Special considerations of antibiotic prescription in the geriatric population, Clinical Microbiology and Infection (2014), http:// dx.doi.org/10.1016/j.cmi.2014.08.018
