Infections remain a major threat to the
wellbeing of our elderly population. Global population is
aging. By 2050, 21.4% of people are projected to be aged 60
years or older [1]. The number of hospitalization with
infectious disease was estimated to be 21.4 million from 1990
through 2002 [2].
Elderly people more than 60 years of age are at increased risk
of having or dying from virtually every serious disease such
as pneumonia, meningitis, endocarditis, cellulitis, infections
of the urinary and gastrointestinal tracts. Many of these
infections are preventable and if diagnosed and treated
promptly in the early stage, mortality may be comparable to
that in young adults. Malnutrition, immune senescence, chronic
medical problems (example diabetes, chronic lung disease,
congestive heart failure, malignancy and dementia) and the
atypical presentation of many life threatening infections in
the elderly are important factors influencing the mortality.
Immune senescence develops insidiously. Its effect on
health often manifests during intense
physiological stress (surgery, multiple organ failure, protein
energy malnutrition and dehydration). A causal relationship
between immune senescence and reactivation of infectious
diseases (example herpes zoster, tuberculosis) is clearly
established.
Between 45 and 80 years of age there is a fivefold increase in
the incidence of herpes zoster due to age related loss
of cellular immunity to the varicella zoster virus. In
residents of long term care facilities there is
reactivation of Epstein Barr virus infection, nosocomial
infections (example methicillin-resistant Staphylococcus
aureus) and health care associated infections (example
catheter associated urinary tract infection). Elderly persons
are also susceptible to parasitic infections due to
immunosenescence.
Apart from immunosenescence pathophysiologic, structural and
functional alterations of different organs also determines the
specific location of some infections. An impaired cough
reflex, reduced mucociliary clearance, altered microbial flora
and increased colonization of the oropharynx leads to severe
respiratory tract infection independent of immune function.
The loss of bacteriostatic properties of urine together with
the reduced ability of kidney to acidify urine and incomplete
emptying of bladder render elderly person susceptible to
urinary tract infection.
Similarly age related changes in the gastrointestinal tract
(example achlorhydria and diverticulae) may predispose to the
development of gastrointestinal infections.
Role of gut microbiome
The gut microbiome is closely associated with several features
of gut barrier integrity, intestinal pro and anti-inflammatory
balance, immune and cardio-metabolic health and gut brain axis
[3].
These old age related clinical problems could clearly
contribute to the increased predisposition to various
infections and gut associated disease by causing alteration in
the microbiota of elderly people.
Symptoms and signs of suspected infection
Typical symptoms and signs of infection are absent in the
elderly. As one ages, becomes frailer, the basal body
temperature decreases.
Infection should be suspected in elderly by
1. Decline in functional status defined as new or
increasing confusion, incontinence, falling, deteriorating
mobility, reduced food intake and failure to cooperate with
others.
2. Fever: Defined as single oral temperature > 100
degrees F (> 37.8 degrees C), Repeat oral temperature
>99 degrees F (>37.2 degrees C) or increase in
temperature of >2 degrees F over the base line
temperature.
Clinical Evaluation
Assessment of respiratory rate
Hydration status
Mental status
Examination of oropharynx and conjunctiva
Skin (Sacral, perineum or perirectal area)
Chest, heart, abdomen and indwelling devices (if present)
Laboratory tests
Complete blood cell count and peripheral blood smear must be
done within 12-24 hours of onset of symptoms. Presence of an
elevated white blood cell count (14,000 cells/ mm
3),
left shift or a total band neutrophil count more than 15,000
cells/mm
3 warrants a careful assessment of
bacterial infection [4].
In the absence of fever, leucocytosis and/or left shift or
specific clinical manifestation of a focal lesion, additional
diagnostic tests may not be indicated, because of low
potential yield. However non bacterial infections cannot be
excluded.
Urinary tract infection (UTI)
As patients age, it is increasingly common to encounter
positive urine cultures without evidence of an infection. In
community, asymptomatic bacteriuria is estimated as >20%
for women aged ≥ 80 years and between 6% to 15% for men aged
>75 years [5]. In long term care facilities, asymptomatic
bacteriuria is present in 25-50% of female and 15-40 % of male
residents.
A number of studies indicated that antibiotic
therapy is not beneficial in asymptomatic bacteriuria
[6].
By treating asymptomatic bacteriuria, two issues emerge:
1) Treatment is usually followed by a rapid
relapse of bacteriuria.
2) Adverse effects of antibiotic administration in older
individuals are frequent.
However one has to distinguish asymptomatic bacteriuria from
UTI. Older adults are less likely to present with classic UTI
symptoms such as dysuria and increased frequency [7].
Functional symptoms such as confusion and falls may be seen in
older adults with UTI. They may exhibit symptoms like fever,
rigors, dysuria, increased frequency, urinary retention and
suprapubic or flank pain, which can aid in the diagnosis of
UTI.
In a study published in European Journal of clinical
microbial infectious diseases 2007 for identifying the risk
for bacteremia with UTI, 5 variables were noted to be
predictive [8].
1. Home residence
2. Foley's catheter
3. Presence of bands in peripheral blood
4. Shaking chills
5. Neutrophilia
Urine analysis and urine cultures should not be performed for
asymptomatic residents in long term care facilities.
Appropriately collected urine specimen includes a midstream or
clean catch specimen obtained from elderly men who are
co-operative and functionally capable. Sometimes a clean
condom external collecting system may be necessary.
For women an in and out catheterization may be necessary.
Urine analysis for determination of leucocyte esterase and
nitrite level can be done by using dipstick and microscopic
examination for WBCs. If pyuria (> 10 WBC/HPF) or a
positive leucocyte esterase or nitrite test is present in
dipstick, only then should a urine culture to be done. If
urosepsis is suspected urine and paired blood specimens should
be obtained for culture and antibiotic susceptibility testing
and gram staining of uncentrifuged urine should be requested.
Ambulatory elderly and other ambulatory patients are almost
similar. In nursing homes, the bacteria grown were similar to
those that were seen in hospital settings. (E. coli,
Klebsiella and Proteus). Dysuria is a usual accompaniment of
bacteriuria but 40% of women with pyuria were not bacteriuric
[9].
Outpatient therapy is similar to young individuals with UTI.
More resistant organisms are obtained from the urine of
nursing home residents, individuals who have received previous
antibiotic therapy, patients with recurrent UTI and recently
hospitalized patients. Apart from gram negative organisms,
both Staphylococcus aureus and Enterococci are causes of
clinical UTI in elderly. Parenteral therapy is given for
individuals who are ill requiring inpatient care. If gram
negative organism are revealed on gram staining, broad
spectrum β-lactum agents with activity against Pseudomonas
(ceftazidime, piperacillin-tazobactum) or ciprofloxacin would
be a good initial therapeutic choice.
All depends upon the prevalence of Extended Spectrum
Beta-Lactamase (ESBL) or methicillin-resistant Staphylococcus
aureus (MRSA) organism in the hospital or in the community and
advice must be obtained from antimicrobial stewardship
programmer in the hospital. It also depends in the
antimicrobial resistance pattern in the locality and in the
hospital. If gram positive organisms are grown, vancomycin
would be appropriate.
People with infection due to multiple drug resistant gram
negative bacteriae can be treated with imipenem/meropenem or
broad spectrum β- lactam agent with an aminoglycoside after
checking for renal functional status and necessary dose
modification. Low dose even (1 mg/kg/day) of aminoglycoside
may be used effectively because of the dramatic concentration
of these agents in the urine.
If fever persists or patients condition does not improve, an
obstruction or perinephric abscess must be ruled out. Catheter
associated bacteriuria is usually caused by multiple bacterial
species and blocked catheter must be changed. Catheterization
should be avoided whenever possible.
If patients with indwelling catheters have symptomatic
infection, they should be treated empirically with one of the
agents discussed. 3-5 days course of antibiotics therapy for
older women with bladder infection is recommended. In men
prostatic focus must be excluded and antibiotic treatment must
be continued for 14 days.
Pneumonia
Pneumonia can be community acquired or nosocomial and is
associated with significant mortality due to delay in the
initiation of antibiotic therapy because of the nonspecific or
atypical presentation of pneumonia in elderly patients.
An altered mental status may be the first sign of pneumonia.
Cough, pleuritic chest pain, fever and leukocytosis are
commonly absent in elderly patients with pneumonia. Findings
associated with poor prognosis in elderly patients with
community-acquired pneumonia are:
[10]
Patients aged more than 50 years
Body temperature less than 35 and > 40 degrees C
PaO2 < 60 mmHg,
O2 saturation < 90 %,
Altered mental status
Tachycardia ≥ 125/ minute
Tachypnea ≥ 30/ minute
Blood pressure < 90 mm Hg systolic
WBC count >13000/cumm or < 4000/cumm
Hematocrit < 30%
BUN ≥ 30 mg/dl
Blood glucose ≥ 250 mg/dl
Sodium < 130 mEq/l
Radiographic evidence of progressing or multi lobar
infiltrates, pleural effusion
Associated co-morbid illness like neoplastic disease,
renal disease, liver failure, congestive heart failure and
cerebrovascular disease carries poor prognosis
The bacterial causes of pneumonia are also different from
those of pneumonia in younger age groups. Both staphylococcal
and gram negative pneumonia seems to be common in older
individuals. Streptococcus pneumonia and gram negative
bacteriae (Haemophilus influenzae, Moraxella catarrhalis and
E.coli) are responsible for most of the lower respiratory
infections in elderly.
Empiric antibiotic therapy should provide coverage for both
gram positive and gram negative bacteriae and macrolide
(erythromycin) may be added if clinical signs suggests
Legionella or pneumophilia infection.
Viral pneumonia
Viral pneumonias are relatively infrequent in the elderly in
comparison with young adults except pneumonia due to
respiratory Syncytial virus. Complications of influenza virus
is more in elderly individuals, who can be protected with
vaccination.
How to diagnose pneumonia?
Because of the increased mortality rate and also due to a
large number of potential pathogens causing pneumonia in the
elderly, early etiological diagnosis is mandatory. Both sputum
and blood should be cultured. Gram stain of sputum is also
useful. The value of a gram stain and routine bacterial
cultures of sputum from patients with Pneumonia is debated and
obtaining adequate sputum specimens from older patients may be
difficult.
Quantification of cultured pathogens and correlation with the
gram stain may help the physician to interpret possible
oropharyngeal contaminants from true pneumo pathogens [11].
Bronchoalveolar lavage should be considered for obtaining a
sputum specimen if required. Pulse oximetry should be
performed for patients with clinical symptoms and respiratory
rate > 25 breaths/minute to document hypoxemia especially
in residents of long term care facilities, so that they can be
transferred to an acute care facility.
Chest radiography must be performed if hypoxemia is documented
or suspected to identity the presence of a new infiltrate
compatible with acute pneumonia and to exclude other
conditions (example multilobar infiltrates, large pleural
effusion, congestive heart failure or mass lesion). At the
onset of a suspected respiratory outbreak especially in a long
term care facility, swab should be obtained from throat and
nasopharynx for rapid diagnostic tests for influenza A virus
and other common viruses. As imaging findings may be less
reliable in older adults, the combination of careful history,
physical examination and noninvasive testing still facilitates
the diagnosis of pneumonia in most elderly patients even in
the presence of atypical clinical presentation.
Infective endocarditis (IE)
Over one half of patients with IE are older than 60 years of
age. The reasons for this predilection for the elderly appear
to include:
1. Surgically implanted valve and prosthetic
material.
2. Use of intravascular devices.
3. The longer survival of patients who have underlying
valvular heart disease
Mortality associated with IE is higher in older patients than
younger individuals. It is difficult to diagnosis IE in older
patients as they present with nonspecific symptoms like:
Confusion
Weight loss
Malaise
Tiredness
Classical physical signs like:
Splenomegaly
Osler's nodes
Janeway lesion
Conjunctival hemorrhage are less likely to be present
Embolic events were found in 15% of older adults compared with
21% of younger adults. Trans Esophageal Echocardiography
revealed evidence of IE in 20 % patients ≥ 70 years of
age in comparison to 14% in patients between 50- 69 years of
age and 12% in patients < 50 years [12]. Hence, when
blood cultures are positive and IE is suspected TEE is
required for the definitive diagnosis. Enterococci,
Staphylococci and Streptococci are usually the etiologic
agents in prosthetic valve endocarditis. A high proportion of
patients with Streptococcus bovis endocarditis were found to
have colonic carcinoma.
Bacteremia
It is more frequent and more fatal in older individuals. The
commonest sources of bacteremia in elderly are the urinary
tract, intra-abdominal sites and the lungs. The organisms
recovered from blood culture, when performed in highly
suspected cases include:
1. Staphylococci, streptococci (patient with skin
infection)
2. Gram negative bacteria or Enterococci (patients with UTI)
3 Anaerobes or gram negative organism (patients with biliary
or other intra-abdominal source of infection), Streptococcal
pneumoniae, H. Infleunzae, gram negative enteric organisms,
Staphylococcus aureus (pulmonary infection)
Infective diarrhoea
Diarrhoea is common in institutionalized older adults.
Clostridium difficile, Shigella, Salmonella and Rota virus
have been implicated as etiological factors.
What are the reasons?
1. Achlorhydria
2. Decreased intestinal motility associated with medication
3. Misuse and abuse of antibiotics disturbing the gut
microbiota
Risk of death associated with diarrhea is higher in older
individual.
Meningits
Case fatality is increased in older patients with meningitis.
One study reported fatality rate of 55 % among the elderly
versus overall case fatality rate of 10 % [13].
The causative organisms include:
Streptococcus pneumoniae
Mycobacterium tuberculosis
Gram negative bacilli
Neisseria meningitidis and H. influenzae are uncommon causes.
Penicillin resistance is demonstrated in elderly with
meningitis. Empiric therapy must include antibiotics effective
against streptococcus pneumoniae, gram negative bacilli and
Listeria monocytogenes.
Septic arthritis
About one quarter of patients with septic arthritis is older
than 60 years of age. Septic arthritis is usually seen in
patients with damaged joints due to Rheumatoid arthritis or
degenerative joint disease. Pain and muscle spasm are less
pronounced. Usual organism is Staphylococcus Aureus. Gram
negative bacilli may also be present.
Pyrexia of Unknown Origin (PUO)
Blunting or absence of diagnostically useful symptoms and
signs including fever is a salient feature of the clinical
presentation of serious infection in elderly. When fever is
the presenting symptoms in elderly, a proper history and
methodical clinical examination are absolutely essential to
find out the site and the etiology. In the absence of any
localizing symptoms or signs occult bacterial infection must
be suspected in the elderly with the new onset of fever. The
first possibility being an occult bacterial infection, early
empiric antibiotic therapy must be instituted after collecting
2 or 3 blood samples for culture of both aerobic and anaerobic
organisms.This should be followed by prompt radiologic
assessment (X ray, CT even PETCT) looking for evidence
of genitourinary, hepatobiliary, abscess associated with
large bowel disease.(diverticulitis or malignancy of colon).
Apart from occult bacterial infection, connective tissue
disorders like vasculitis, giant cell arteritis and
intra-abdominal lymphoma must also be considered.
The antibiotics recommended as initial therapy for the elderly
are as follows: [14]
Community acquired pneumonia - 3rd generation
cephalosporin
Urinary tract infection by gram negative organisms -
3rd generation cephalosporin, broad spectrum penicillin with
beta lactamase inhibitor, trimethoprim-sulphamethexazole or
quinolone
Urinary tract infection by gram positive organism -
vancomycin is preferred as it is active against
Enterococci, staphylococci and streptococci
Vancomycin with gentamycin is the preferred combination
for infective endocarditis which can be modified as per
blood culture and sensitivity report
Infectious diarrhoea - can be treated with ciprofloxacin
or other quinolone
Bacterial meningitis is treated by third generation
cephalosporin and can be combined with ampicillin if
Listeria monocytogenes is suspected
Septic arthritis - nafcillin or vancomycin
Pressure sores may require broad spectrum beta lactam with
beta lactamase inhibitor. Other treatment regimens against
bacteroides staphylococci also may be considered
For acute fever with unidentified source imipenem
/meropenem may be useful
According to a recent FDA warning, there is an association
between quinoline antibiotic use and aortic aneurysm and
dissection especially in elderly with hypertension,
atherosclerotic PVD. Hence it is better to withhold
quinolones in the elderly.
Skin infections - Herpes Zoster
It is caused by a reactivation of varicella virus lying
dormant in the dorsal root ganglia is common in older adults
due to waning of cellular immunity. Post herpetic neuralgia
can be debilitating in older patients and develops in 10 -70 %
of patients which will be difficult to treat [15]. Antiviral
therapy with famciclovir, valcyclovir and acyclovir initiated
within 72 hours after the appearance of the rash can reduce
the acute pain and can reduce the duration of eruption.
Methicillin resistant staphylococcal (MRSA) infection
MRSA infection is a major problem in elderly patients
especially for those in institutional settings. People
colonized with MRSA are at increased risk of infection with
sepsis. They also have higher risk of death due to antibiotic
resistance. Hand washing, isolation of infected patients and
proper handling of bodily secretions are essential to prevent
the spread of MRSA. The most common reservoirs are the nasal
mucosa and oropharynx. Active infection with MRSA requires
treatment with vancomycin while colonization does not require
systemic treatment. Nasal carrier can be eradicated with local
application of mupirocin ointment. Other regimens include
vancomycin + gentamycin or rifampin.
Vancomycin Resistant Enterococcus (VRE)
Enterococci are the second most common organism in nosocomial
urinary tract and wound infections. Most enterococci have
become resistant to β lactam antibiotics as well as to
aminoglycosides. For the treatment of multidrug resistant
Enterococci in older adults, glycopeptide antibiotics like
vancomycin and teicoplanin have become the most reliable
antibiotics.
Bacteremias from these isolates have a mortality rate up to
50%. Multiple strains for VRE are recognised now. Phenotypes
Van A, Van B, Van C are described. For Van A, VRE combination
of ampicillin and imipenem, vancomycin and ciprofloxacin,
ceftriaxone with fosfomycin and chloramphenicol have been used
with limited success. A combination of teicoplain with
gentamycin has been successful.
Proper infection control practices, hand washing and proper
handling of bodily secretions, isolation of carriers and
restricting the use of oral and parenteral vancomycin will
help to control further spread of resistance.
Empirical antibiotics therapy
General principles
1. Avoid aminoglycoside therapy for older
individuals because many safer and less toxic alternatives
are available.
2. Because of the decreased hepatic and renal function in
older individuals, doses of antibiotics that are somewhat
lower than the maximum dose that might be employed for
younger individuals can be used.
3. Broad spectrum antimicrobial agent may be initiated until
an eitiological diagnosis is established.
4. Early administration of appropriate antimicrobials has
been postulated as a key strategy associated with survival
of patients with severe infections, when the clinical
manifestations will be subtle or nonspecific.
Prevention
A healthy life style with regular exercise, balanced diet with
careful attention to personal hygiene and regular medical care
will be helpful in preventing infections in the older adults.
UTI is preventable by limiting the use of urinary catheters
and providing topical estrogen therapy for women and
pharmacological or surgical relief of prostatic hypertrophy
for men. Most important is to have awareness of these
components of preventive measures among physician who are
involved in geriatric care.
Specific recommendation is adult immunization at appropriate
interval even though the response to vaccination is poor.
Diphtheria + Tetanus Toxoid should be administered every 10
years.
Recommendation for prevention against S. pneumoniae infections
usually include sequential applications of 13 valent
conjugated pneumococcal vaccine given before 23-valent
Polysaccharide vaccine for those > 65 years.
Annual vaccination against influenza with Tri or Quadrivalent
vaccine is recommended for those > 60 years. In European
countries and USA this vaccination is available without age
restriction (> 6 months). Though the clinical protection
offered does not persist throughout the year after influenza
vaccination, elderly people are the main focus of prevention
strategies because they are highly vulnerable to the
complications.
A new universal influenza vaccine (Hissf _ 3928) enters human
trials and if it proves to be effective, it can provide long
lasting protection for all age groups from multiple influenza
subtypes. (No further need for annual vaccination).
A live attenuated Zoster vaccine has been available since 2006
has been shown to reduce disease incidence by 51.3% and post
herpetic neuralgia by 66.5% after single shot application. It
is contraindicated in immunocompromised patients [16].
A new recombinant zoster vaccine has been licensed recently in
US and Canada and provides efficacy in all age groups and
immunocompromised patients [17].
Conclusion
Infections in older adults are common and they may present in
unusual way. An early prompt, intensive and laborious
diagnostic work up is essential. Multiple co-morbidities and
polypharmacy potentially results in drug interaction, altered
drug metabolism, and subsequent toxic effects of drug
accumulation must be considered while caring for elderly
patients. Though an early empirical antimicrobial regimen is
essential to prevent mortality, a shift from Empiric treatment
to a focus on diagnosis is essential, as several
non-infectious complications in the elderly may alter the
course and severity of infections in older patients.
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