Infection and Immunity

The ageing immune system

The immune system ages in a complex manner:

Some activities increase (eg production of memory T lymphocytes, IgA, and autoantibodies)
Other activities diminish (eg production of some interleukins, antibodies in response to foreign antigens, macrophage clearance of antigens, and complement during acute infection)
Overall, immune responses become less efficient, less appropriate, and occasionally harmful with age
The immune system does not wear out—it becomes dysfunctional
This is an insidious process, often unnoticed until times of physiological stress (eg acute illness)
It is more marked in older people with chronic disease, multiple comorbidities and significant genetic and environmental factors

This immune dysfunction alters the response to infection in older people:

Infectious disease is a more significant cause of morbidity and mortality in older people (up to 10 times more likely to be the cause of death)
Impaired cellular immunity predisposes older people to reactivation of certain diseases eg:
- Shingles (see ‘Varicella zoster infection’, p.624)
- Tuberculosis (see ‘Tuberculosis: presentation’, p.336)
Altered antibody production increases fatality from pneumonia, influenza, bacterial endocarditis, and hospital-acquired infections
Decreased levels of lymphokines increase susceptibility to parasitic infections
Age-related immune dysfunction probably has a negative impact of the course of AIDS in older patients (see ‘HIV in older people’, p.530)

▶Investigations may not show characteristic changes associated with infection, or these changes may develop more slowly (eg rise in white cell count, CRP, and complement).

It also has other clinical consequences:

Increased autoantibody production does not lead to an increase in autoimmune disease (this peaks in middle age), but may contribute to degenerative diseases
Response to vaccination may be less good
Falling immune surveillance may contribute to higher cancer incidence
T lymphocyte dysfunction may contribute to the increasing incidence of monoclonal gammopathy with age (see ‘Paraproteinaemias’, p.459)
IgE-mediated hypersensitivity reactions are less frequent, so allergic symptoms tend to improve with age

Overview of infection in older people

Susceptibility to infection is increased by:

Immune senescence (see ‘The ageing immune system’, p.606)
Altered skin and mucosal barriers
Acute and chronic illnesses (cause relative immunosuppression)

Blunted response to infection may occur in those with:

Decreased cardiac adaptation to stress
Comorbid conditions and frailty
Decreased lean body mass or malnutrition
Multiple previous hospital admissions or residence in a long-term care facility

Presentation

Frequently atypical eg global deterioration, non-specific functional decline, delirium, falls, incontinence
May initially give no clue to the site of sepsis, eg chest infections may present with falls, rather than cough
Fever is often absent, reduced, or delayed (due to senescent hypothalamic and other responses)
Often indolent with a slow deterioration over several days

▶By the time sepsis is obvious, the patient may be very unwell.

Investigation

Obtaining samples can be difficult, eg delirious uncooperative patient, urinary or faecal incontinence, inability to expectorate sputum, etc.

Misleading results are common:

Positive urine dipstick often does not indicate symptomatic infection (see ‘Near-patient urine tests’, p.618)
Urine samples from a catheterized patient will usually be heavily colonized; dipstick tests will be positive and culture results difficult to interpret
Ulcers will usually be colonized and swab results should be interpreted with caution (see ‘Leg ulcers’, p.593)
Abdominal ultrasound scan will often reveal gallstones in older patients—these are usually asymptomatic and do not necessarily imply biliary sepsis
Classical markers of infection (leucocytosis, elevated CRP, increased complement) may be absent or delayed in older patients. Repeating them after 24hr improves sensitivity

Treatment

Because of the difficulties in making an accurate diagnosis:

Therapy is often empirical
Antibiotic failures are more common
Antibiotic resistance frequently develops

In addition, treatment may be difficult to administer in delirious patients.

HOW TO … Accurately diagnose infection in an older patient

Making an accurate diagnosis with evidence to support it is important to allow tailored antibiotic therapy. Have a low threshold for considering sepsis as a cause for decline of any sort, but conversely do not assume that all problems stem from infection.

Investigations

Full blood count—white cell count may be elevated, suppressed (poor prognostic indicator) or be unchanged
ESR, CRP—often become elevated early on in infection, but this is very non-specific and they may take 24-48hr to rise or remain normal. Serial measurements advised
U,C +E—septic older patients are prone to renal impairment
Blood and urine cultures—send before antibiotics are started and even in the absence of fever
CXR—a patch of consolidation on an X-ray may be the first indicator that a global deterioration is due to pneumonia
Consider stool analyses (if diarrhoea)

If the source remains unclear, repeat basic tests, then consider:

Skin—check carefully for cellulitis and/or ulceration (see ‘Cellulitis’, p.589)
Bones—osteomyelitis (particularly vertebral, after joint replacement or where there is chronic deep ulceration of skin) may present indolently. Check for bony tenderness and consider X-rays, bone scans, or MRI (see ‘Osteomyelitis’, p.488)
Heart valves—bacterial endocarditis can be very hard to diagnose. Consider in all with a murmur, and actively exclude in those with prosthetic heart valves
Biliary tree—asymptomatic gallstones are common in older patients, but if an ultrasound also shows dilatation of the gall bladder or biliary system with a thickened, oedematous wall, then infection is likely. There is usually (but not always) abdominal pain. Send blood cultures. ERCP may be needed to remove any obstruction
Abdomen—diverticulosis is common, and abscesses may present atypically. Examine for masses and consider abdominal ultrasound or CT if there is a history of diverticulae or abdominal pain
Brain—meningitis, brain abscess, and encephalitis may present indolently in older patients, and the usual warning signs (confusion, drowsiness) may be misinterpreted. Headache and photophobia may be late or absent, and neck stiffness difficult to interpret. Consider CT head followed by CSF analysis if a septic patient has focal neurology, headache, photophobia, or bizarre behavioural change
TB—may reactivate in older people and cause chronic infection. If there is known previous TB (clinical or CXR evidence) then look very carefully for reactivation. Consider early morning urines, sputum culture (induced if necessary), bronchoscopy, or biopsy of any abnormal tissue (eg enlarged lymph nodes)

▶Remember that fever and raised inflammatory markers can also be due to non-infectious conditions (eg malignancy, vasculitis, etc.)

Antibiotic use in older patients

Antibiotics are among the most frequently prescribed drugs, and their widespread use is promoting increasing antibiotic resistance.

This is a particular problem in older patients where infections are more common, yet accurate diagnosis can be more difficult.

Antibiotic resistance

Resistance is encouraged by:

‘Blind’ antibiotic therapy (where likely microbe and sensitivities are not known)
Inappropriate antibiotic therapy (eg for viral respiratory infections)
Inadequate treatment courses
Poor concordance with therapy
Transmission of resistant strains within healthcare settings

Sensible antibiotic prescribing

Helps to limit the problem. Applies to all ages, but may be more of a challenge in older patients:

Make a diagnosis—identify the source of sepsis (and so possible pathogens), which will guide therapy before microbiological confirmation is obtained
Avoid antibiotics for infections that are likely to be viral, eg pharyngitis, upper respiratory tract infection
Where practicable, send samples for culture and sensitivity before initiating antibiotics
Local variations (eg diagnostic mix, local sensitivities) should be considered. Use local antimicrobial guidelines
Choose the dose based on the patient (allergies, age, weight, kidney function, etc.) and the severity of the infection. Inadequate doses promote resistance
Choose the route—aim for oral wherever possible, and convert iv therapy to oral as soon as feasible; im antibiotic therapy is uncomfortable but can be useful (eg cognitively impaired patients who refuse oral medication)
Choose the duration based on the type of infection, eg simple UTI can be adequately treated in 3 days, whereas bacterial endocarditis can require many weeks of therapy. Unnecessarily long treatment courses will promote resistance, increase the risk of side effects, complications (eg CDAD) and increase cost
Change empirical broad-spectrum antibiotics to narrow-spectrum alternatives as soon as sensitivities are known