Infection and Immunity
The ageing immune system
The immune system ages in a complex manner:
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Some activities increase (eg production of memory T lymphocytes, IgA, and autoantibodies)
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Other activities diminish (eg production of some interleukins, antibodies in response to foreign antigens, macrophage clearance of antigens, and complement during acute infection)
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Overall, immune responses become less efficient, less appropriate, and occasionally harmful with age
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The immune system does not wear out—it becomes dysfunctional
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This is an insidious process, often unnoticed until times of physiological stress (eg acute illness)
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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:
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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)
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Impaired cellular immunity predisposes older people to reactivation of certain diseases eg:
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Shingles (see
‘Varicella zoster infection’, p.624)
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Tuberculosis (see
‘Tuberculosis: presentation’, p.336)
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Altered antibody production increases fatality from pneumonia, influenza, bacterial endocarditis, and hospital-acquired infections
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Decreased levels of lymphokines increase susceptibility to parasitic infections
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Age-related immune dysfunction probably has a negative impact of the course of AIDS in older patients (see
‘HIV in older people’, p.530)
It also has other clinical consequences:
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Increased autoantibody production does not lead to an increase in autoimmune disease (this peaks in middle age), but may contribute to degenerative diseases
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Response to vaccination may be less good
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Falling immune surveillance may contribute to higher cancer incidence
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T lymphocyte dysfunction may contribute to the increasing incidence of monoclonal gammopathy with age (see
‘Paraproteinaemias’, p.459)
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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:
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Immune senescence (see
‘The ageing immune system’, p.606)
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Altered skin and mucosal barriers
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Acute and chronic illnesses (cause relative immunosuppression)
Blunted response to infection may occur in those with:
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Decreased cardiac adaptation to stress
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Comorbid conditions and frailty
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Decreased lean body mass or malnutrition
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Multiple previous hospital admissions or residence in a long-term care facility
Presentation
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Frequently atypical eg global deterioration, non-specific functional decline, delirium, falls, incontinence
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May initially give no clue to the site of sepsis, eg chest infections may present with falls, rather than cough
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Fever is often absent, reduced, or delayed (due to senescent hypothalamic and other responses)
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Often indolent with a slow deterioration over several days
Investigation
Obtaining samples can be difficult, eg delirious uncooperative patient, urinary or faecal incontinence, inability to expectorate sputum, etc.
Misleading results are common:
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Positive urine dipstick often does not indicate symptomatic infection (see
‘Near-patient urine tests’, p.618)
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Urine samples from a catheterized patient will usually be heavily colonized; dipstick tests will be positive and culture results difficult to interpret
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Ulcers will usually be colonized and swab results should be interpreted with caution (see
‘Leg ulcers’, p.593)
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Abdominal ultrasound scan will often reveal gallstones in older patients—these are usually asymptomatic and do not necessarily imply biliary sepsis
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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:
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Therapy is often empirical
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Antibiotic failures are more common
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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
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Full blood count—white cell count may be elevated, suppressed (poor prognostic indicator) or be unchanged
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U,C +E—septic older patients are prone to renal impairment
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Blood and urine cultures—send before antibiotics are started and even in the absence of fever
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CXR—a patch of consolidation on an X-ray may be the first indicator that a global deterioration is due to pneumonia
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Consider stool analyses (if diarrhoea)
If the source remains unclear, repeat basic tests, then consider:
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Skin—check carefully for cellulitis and/or ulceration (see
‘Cellulitis’, p.589)
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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)
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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
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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
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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
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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
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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)
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:
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‘Blind’ antibiotic therapy (where likely microbe and sensitivities are not known)
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Inappropriate antibiotic therapy (eg for viral respiratory infections)
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Inadequate treatment courses
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Poor concordance with therapy
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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:
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Make a diagnosis—identify the source of sepsis (and so possible pathogens), which will guide therapy before microbiological confirmation is obtained
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Avoid antibiotics for infections that are likely to be viral, eg pharyngitis, upper respiratory tract infection
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Where practicable, send samples for culture and sensitivity before initiating antibiotics
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Local variations (eg diagnostic mix, local sensitivities) should be considered. Use local antimicrobial guidelines
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Choose the dose based on the patient (allergies, age, weight, kidney function, etc.) and the severity of the infection. Inadequate doses promote resistance
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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
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Change empirical broad-spectrum antibiotics to narrow-spectrum alternatives as soon as sensitivities are known
Further reading
British National Formulary (BNF) Section 5.1 Antibacterial drugs.
Meticillin-resistant Staphylococcus aureus
Meticillin was introduced in the 1960s to treat staphylococcal infections. It was used widely (including spraying solutions into the air on wards) and initially successfully. Meticillin has now been discontinued and replaced by flucloxacillin but the term MRSA persists.
Resistance to meticillin gradually emerged—firstly small numbers within hospitals, but the problem slowly increased and spread into the community, until globally dispersed epidemic strains emerged.
All staphylococci are easily transmissible, virulent (capacity to cause disease) and have capacity to develop further antibiotic resistance.
The problem today
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Varies enormously eg > 25% of invasive Staph. aureus isolates are resistant in UK, Spain, and Italy, compared with <1% in Scandinavia
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However, rates peaked in 2005/6 and are now reducing—deaths where MRSA was mentioned on death certificates have decreased from > 1600/year to <800/year between 2005 and 2009
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MRSA reduction continues to be a political target in the UK
Contamination and transmission
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Transient carriage on the gloves or hands of healthcare workers is likely to represent the main mode of transmission to other patients
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Up to 35% of environmental surfaces in a room being used by an MRSA patient will culture positive (role in transmission is unclear)
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Decontamination involves cleaning. Good hand hygiene and the use of alcohol hand gel after patient contact reduce transmission significantly
Colonization
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This is asymptomatic carriage of MRSA. Patients and families often need reassurance that this rarely has implications for the patient
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Common sites are anterior nares, perineum, hands, axillae, wounds, ulcers, sputum, throat, urine, venous access sites and catheters
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Duration of colonization varies from days to years
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Transmission from a colonized person is more likely if there is a heavy bacterial load with abnormal skin (eg ulcers, eczema), devices (eg catheters, cannulae) or sinusitis/respiratory tract infection
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Many healthcare workers are colonized (usually nasal) and are a potential reservoir, but usually colonization is short lived so that screening healthcare workers is only useful for investigating specific outbreaks
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Screening for MRSA colonization is now routine practice prior to elective procedures and for most hospital admissions especially interhospital transfers. Eradication of MRSA may follow; treatment regimens include the application of nasal mupirocin, antimicrobial soaps and sometimes oral antibiotics (eg fusidic acid, rifampicin)
Disease caused by MRSA
The most common sites of infection are:
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Wounds—most common cause of postoperative wound infections
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Intravenous lines—often leading to bacteraemia
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Ulcers—including pressure, diabetic, and venous ulcers
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Deep abscesses—infection can seed to many sites, eg lungs, kidneys, bones, liver, and spleen
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Bacteraemia—there is compulsory reporting
30-60% of hospital patients colonized with MRSA will go on to develop infection. This is more likely if there has been:
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Recent prior hospitalization
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Surgery or wound debridement
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Invasive procedures (including venepuncture and venous cannulation)
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