Diagnosis and management of hospital-acquired pneumonia in older adults

Pneumonia is usually caused by bacterial or viral infection, resulting in inflammation of the lungs (see Figure 1). Pneumonias represent a major medical and economic problem because they are the most frequent causes of morbidity and mortality worldwide^[1]
, particularly in certain patient groups, such as people who are immunocompromised, children and older adults^[2],[3]
.

Pneumonia can be broadly defined as community-acquired (acquired outside hospital or healthcare facilities) and hospital-acquired (acquired after 48 hours of admission to hospital)^[1]
. The former can be caused by viruses; atypical bacteria (bacteria that are neither Gram-negative nor Gram-positive), including Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila; and fungi. Hospital-acquired pneumonia (HAP), although acquired in hospital, is considered distinct from pneumonia associated with mechanical ventilation, which is known as ventilator-associated pneumonia (VAP)^[1]
.

An ever-increasing ageing population means that a greater proportion of individuals will be treated for respiratory tract infections, thus increasing the societal burden of this disease^[4],[5]
. HAP increases the length of in-patient hospital stay and has been estimated to be the ‘attributable cause’ of death in between a third and a half of patients who are diagnosed with it.

This article will focus on the diagnosis and management of HAP episodes in older adults. It aims to support pharmacists and healthcare professionals in appropriately diagnosing and managing the condition.

Aetiology and epidemiology

The spectrum of organisms known to cause HAP and other respiratory infections is broad and constantly increasing. New pathogens are constantly being identified. However, it is frequently difficult for healthcare professionals to identify the causative organism for the pneumonia, as the patient’s immune response can be altered by medicines and other diseases^[5]
. Even with a full range of microbiologic tests, the causative organisms can currently only be identified in around 30–70% of cases^[5]
.

Viral and fungal aetiologies are rarer, but incidents for each can be relatively high in certain circumstances, such as in an influenza outbreak^[6]
.

Bacteria, such as Streptococcus pneumoniae or Haemophilus influenzae,  are the most common cause of HAP^[2],[5],[7]
. Pseudomonas aeruginosa, Klebsiella spp., Enterobacteriaceae, 
Escherichia coli, Serratia marcescens and Proteus spp. are common causes of HAP as length of hospital stay increases. HAP is estimated to increase hospital stays by seven to nine days. In addition, as length of hospital stay increases, it is more likely for multi-drug resistant (MDR) organisms to become the cause of the infection; these have increasingly been associated with a higher mortality^[5]
. Furthermore, it has been reported that 5–10 per 1000 patients admitted to hospital develop HAP^[2]
.

Risk factors

Previous intravenous antibiotic use (defined as antibiotic use within 90 days) is a significant risk factor for HAP caused by either methicillin-resistant Staphylococcus aureus (MRSA) or P. aeruginosa
^[1]
. Additional risk factors for P. aeruginosa HAP include a history of chronic obstructive pulmonary disease (COPD), patients chronically colonised with P. aeruginosa, and prior use of carbapenems, broad spectrum cephalosporins or fluoroquinolones.

Ageing results in reduced lung elasticity and respiratory muscle strength (both inspiratory and expiratory); therefore, older patients may struggle to effectively clear their airways making them more prone to respiratory infections. The increase in co-morbidities in older people also adds to host defence impairment. Additionally, functional dependence, cognitive impairment, malnutrition and hypoalbuminaemia add to the risk factors for developing HAP. The role of silent aspiration is increasingly recognised in the pathogenesis of lower respiratory tract infection in older patients^{[2],[8],[9],[10],[11],[12]}
and should be included in differential diagnoses.

Further risk factors contributing to the development of HAP^[8]
can be found in Box 1: ‘Risk factors for hospital-acquired pneumonia’.

Diagnosis

Symptoms

There is considerable variation in the clinical presentation of HAP, rendering distinction from other infections difficult (see Box 2: ‘Common symptoms of pneumonia’). The difficulties in making an accurate diagnosis has decreased the threshold for treatment of HAP, especially in older patients, owing to the high mortality rates associated with the condition^[2]
.

Classic symptoms include fever, blood leucocytosis^[2]
, leucopenia, malaise, cough, sputum production and chest pain. However, in practice, these symptoms may not necessarily be caused by pneumonia^[2],[5],[10]
. Many disorders can mimic pneumonia, meaning that several differentials must be considered and potentially excluded, including pulmonary infarction, pulmonary oedema, pulmonary haemorrhage, pulmonary vasculitis, malignancy, iatrogenic lung shadowing and pre-existing lung disease^{[13],[14],[15]}
.

Generally, the older and more debilitated the patient, the more likely the classic pneumonia syndrome will be incompletely expressed^{[2],[5],[16],[17]}
. Decreased breath sounds, crackles and egophony (increased resonance of voice sounds) are poor diagnostic indicators; these must be combined with assessing vital sign abnormalities if specificity is to be improved. Fever is less commonly observed because many patients may be on regular agents with an antipyretic effect. Clinical observations such as confusion, delirium, tachypnoea (abnormally rapid breathing) and tachycardia are common and may be the only signs a patient exhibits^[11]
.

Biomarkers

Common point-of-care tests used to diagnose the presence of bacterial infections, and whether to initiate antibiotic therapy, include white cell count and C-reactive protein. Procalcitonin (PCT) is emerging as a promising diagnostic biomarker because it is released into the bloodstream during bacterial infection; therefore, high levels can indicate a severe bacterial infection, whereas low levels can indicate a viral infection. Recent Infectious Diseases Society of America and the American Thoracic Society guidelines recommend using clinical criteria alone, rather than using serum PCT plus clinical criteria, to decide whether or not to initiate antibiotic therapy^[1]
. At present, there is not enough evidence to support the addition of procalcitonin testing to standard clinical practice in the NHS^[18]
.

The Clinical Pulmonary Infection Score

The Clinical Pulmonary Infection Score (CPIS) is based on six criteria: fever, leucocytosis, positive sputum culture, worsening chest X-ray, oxygenation [PaO₂/FiO₂] and semi-quantitative cultures of tracheal aspirates, with or without Gram stain. A prospective cohort study investigated the utility of a modified CPIS in the diagnosis of HAP. Conventional clinical diagnosis was found to be inaccurate (sensitivity 50%, specificity 58%) but the CPIS was only slightly more accurate (sensitivity 60%, specificity 59%)^[19]
. CPIS may be useful for selecting patients for short-course therapy and monitoring response to treatment. However, further data are required.

Imaging

A chest X-ray is an important examination in all patients suspected of having an infection. It should be carried out to confirm or exclude the presence of pulmonary abnormalities^{[14],[20],[21]}
in addition to systemic symptoms to aid in the diagnosis. It is widely available, inexpensive and has a low radiation burden, fuelling its popularity for use in clinical investigation. It aids to narrow the differential diagnosis, evaluate complications, helps to direct additional diagnostic measures and serves as an ideal tool for follow-up examinations. Comparison with previous X-rays is useful to determine the presence of pneumonia. If follow-up exams are performed, it is important to consider the time period in which a pneumonic infiltrate may resolve. As a general rule, most pneumonias regress within 10–21 days. However, complete resolution may take up to six months, especially in patients with underlying lung disease (e.g. patients with COPD, immunocompromised individuals and older patients)^[22],[23]
. However, the accuracy of chest X-rays can be limited in hospitalised individuals who have comorbidities; radiologic diagnosis of CAP is relatively straightforward in comparison^[20]
.

It should be noted that the quality of the X-ray plays a critical role in the management of patients with suspected pneumonia^[20]
. Older patients may not be able to inspirate/expirate to full capacity or remain in the necessary position required to ascertain a clear picture. Although some variation exists regarding the timeframe between the onset of clinical symptoms and the development of a radiographically visible abnormality, the vast majority of infiltrates appear within 12 hours^[14]
. Hence, patients who develop symptoms of a pulmonary infection in a hospital setting may be seen within hours after the onset of clinical symptoms and a visible radiographic abnormality may not have developed; in immunocompromised patients the appearance of a detectable radiographic abnormality may be delayed^[24],[25]
. It is important to note that in this group of patients, radiographic patterns change with immunologic status.

Imaging examinations should always be interpreted with a knowledge of how symptomatic the patient is, the degree of dyspnoea, the level of impairment of the carbon monoxide diffusing capacity of the lung, the CD4⁺ cell count, the presence of fever, if there is a cough (and whether it is productive), and the chronicity of symptoms^[2]
.

Radiographically, patchy bronchopneumonia is the most common finding for HAP. Aspiration pneumonia is always an alternative diagnosis and should be suspected if pneumonia is present bilaterally in the dependent or posterior portions of the lungs^[26]
.

In the absence of clinical information, radiologists cannot reliably distinguish between pneumonia and other pulmonary processes^[27]
. Clinical information can greatly enhance the accuracy of a radiological diagnosis.

Pneumonia may exist without the typical appearance of a pulmonary infiltrate on the chest X-ray. Computerised tomography (CT) is more sensitive in the detection of subtle abnormalities and may show findings suggestive of pneumonia earlier than plain chest X-rays^[20]
. CT and invasive diagnostic procedures should be considered in cases of treatment failure or where there are complexities. Computed immunities are reserved for unclear cases, particularly when chest X-rays are normal in patients with a high level of clinical suspicion of pneumonia, and in immunocompromised patients, in whom early diagnosis of pneumonia is important to determine a positive outcome.

Culture and invasive procedures

Sputum secretions are extremely difficult to obtain. They are often too poor quality to be used for culture, and are frequently contaminated by upper respiratory tract flora^[28],[29]
. Therefore, not all organisms isolated from sputum secretions should be regarded as pathogens that necessarily require therapy; they should be interpreted and treated using the full clinical picture and, if necessary, in conjunction with consultant microbiologists. Older patients are generally unable to cough or expectorate, and so produce little or no sputum. Therefore, this approach is essentially ineffective and not cost-effective^[5]
. Although isolation of organisms is helpful to guide treatment, it is not essential for diagnosis of HAP.

Further investigations, such as fine needle aspiration, should only be considered for patients who have not responded to initial treatment, in order to identify the causative organism for appropriate treatment selection^[30],[31]
.

The use of invasive procedures, such as bronchoscopy to identify the potential causative agent, are frequently limited and may carry a high risk, especially in older patients, those that are immunocompromised and/or have coagulation disorders^[5]
.

Treatment

Definitive diagnosis in HAP is difficult. The older and more infirm the patient, the more likely therapeutic difficulties will be encountered^[5]
. Functional status, duration of hospitalisation, and concomitant medical illness are additional factors adding to the complexity and difficulty in treating these patients. If a positive microbiological result is attained, it may not influence outcome or change in therapy, thus raising the question of cost-effectiveness and exposure of risk to patients from procedures used to obtain samples. This has led to widespread empirical treatment^[2],[5]
.

Empiric therapy should be based on local resistance patterns and recommendations. There are a number of antibiotics that are no longer regarded as appropriate empirical therapy for patients with HAP, because of dramatic changes in the nature and susceptibility patterns of the pathogens recognised in most UK hospitals^[2]
. Empirical antibiotic therapy for patients with HAP should also be based on duration of hospital stay, host factors, co-morbidities and recent administration of antibiotic therapy. Similarly, definitive therapy should be determined by culture and susceptibility test results, if possible, but treatment should not be delayed because this has been associated with increased morbidity and mortality rates^[32],[33]
.

There are many limitations in the quality of the available evidence to assist in approaches to antimicrobial selection in HAP. Few studies have compared more than two therapeutic options. Where possible, monotherapy should be used. This will aid in limiting the adverse drug reactions and toxicity that patients may experience. Combination therapy is advocated where activity against resistant organisms is required.

Risk factors should be taken into account when deciding which antibiotics to initiate. For patients being treated empirically for HAP, antibiotics with activity against S. aureus, such as piperacillin/tazobactam, ceftazidime or meropenem, should be prescribed. If risk factors for MRSA exist, the addition of teicoplanin or vancomycin is recommended. If risk factors for P. aeruginosa exist, antibiotics that have activity against these organisms should be prescribed. Specific patient factors, such as allergy status, should also be taken in account when deciding on a regimen.

Renal function must also be considered because many antibiotics are cleared renally. Dose adjustments may be required depending on the degree of renal insufficiency. Local guidelines, expertise and specific summary of product characteristics should be consulted for advice regarding dose and frequency.

Commonly, durations of between five and seven days have been used to treat infections. Increased use and increased treatment durations of antibiotics are known to add selection pressure for bacteria to develop resistance^[4],[5],[34]
. National Institute for Health and Care Excellence (NICE) guidelines recommend a 5‑ to 10‑day antibiotic therapy course for patients with HAP^[7]
. It also recommends that antibiotic therapy should be offered as soon as possible after diagnosis, and certainly within four hours^[7]
.

However, patients should be treated for as long as necessary to resolve the infection. It is not necessary to follow patients radiographically when the clinical course indicates successful treatment. Where treatment failure is indicated, this may be as a result of a complication (e.g. sepsis), incorrect diagnosis or treatment of the wrong pathogen.

Initial treatment for HAP is generally parenteral. Patients should be switched to oral alternatives when they are improving clinically. Local guidelines and expertise (i.e. consultant microbiologist, infectious disease physician and antimicrobial pharmacist) should be consulted regarding the appropriate oral agent(s) to switch patients to. This will facilitate discharge, decrease patient exposure to acquire a hospital-acquired infection or superinfection, and be economically advantageous^[34]
.

Physiotherapy

Chest physiotherapy is commonly used in patients with HAP. It may be of value to patients and might be appropriate as a therapeutic adjunctive option. However, data are lacking on its efficacy.

Prevention

Infection control is important in preventing HAP, for example good hand hygiene for healthcare professionals can help prevent the transmission of MDR pathogens that cause HAP (see Box 3: ‘Hand hygiene’).

Summary

The diagnosis of HAP in older people is difficult, and the criteria used for surveillance have been based on clinical findings of fever, cough, and the development of purulent sputum in combination with a new or progressive infiltrate on the chest X-ray. Each patient should be assessed individually to ascertain the most likely cause, taking into account the patient’s condition and history. Therapy should be led by local guidelines, resistant patterns and patient factors.