Nosocomial pneumonia: a bird’s eye view

Senior Clinical Pharmacist for Medicine

Lead Specialist Infection Prevention and Control Pharmacist,

The Queen Elizabeth Hospital Kings Lynn NHS Foundation Trust, Kings Lynn, UK

Nosocomial, or hospital-acquired, pneumonia (NP) is a respiratory infection that develops more than 48 hours after hospital admission.(1) It includes ventilator-associated pneumonia (VAP), which is defined as a pneumonia that develops 48–72 hours after commencing mechanical ventilation. The incidence of NP is estimated to be between 0.5 and 1.0% of hospital admissions(2); it is associated with a significant increase in the length of hospital stay(3) and significantly increased cost.(4) It is the second most common heathcare-associated infection (HCAI) after urinary tract infections and is the most common HCAI contributing to death.(5) VAP is the most common nosocomial infection found in the ITU with 9–28% of intubated patients developing VAP.(6) It is associated with significant morbidity and a mortality rate of up to 76% in antibiotic-resistant infections.(7)

In the UK, a number of organisations have recognised the importance of reducing the incidence of NP. The Department of Health (DH) ‘Saving Lives initiative’ identified high-impact interventions to reduce the incidence of HCAIs. This includes guidance and tools for the care of ventilated patients to reduce VAP.(8) The National Institute for Health and Clinical Excellence in conjunction with the National Patient Safety Agency (NPSA) have published guidance for implementation in critical care units to reduce the incidence of VAP(9) and in 2006 the British Society for Antimicrobial Chemotherapy (BSAC) published the first UK guidelines for the management of hospital-acquired pneumonia.(1)

Given its high morbidity and mortality, and the high healthcare costs of treating NP, it is important to optimise prevention of NP. The BSAC guidelines consider prevention under four categories:

• General issues
• Use of equipment
• Patient procedures
• Environmental issues.

Studies have shown that the introduction of staff education on measures to be taken to prevent NP can reduce its incidence and the use of care protocols in ICUs can decrease the incidence of VAP, particularly in trauma patients. The DH recommended that ‘care-bundles’ be implemented to allow staff to monitor compliance with clinical guidance and provide the means to ensure that staff undertake clinical procedures correctly every time.(8)

Hand hygiene has been shown to reduce the incidence of all HCAI and it therefore follows that high standards of hand hygiene be maintained by all healthcare staff to reduce the incidence of NP. Appropriate use of personal protective equipment (PPE), in particular gloves, prevents the spread of micro-organisms and HCAI, and therefore should reduce the incidence of NP. It is essential to select the correct PPE, and staff need to be trained in its appropriate use. BSAC recommends that local risk assessment be carried out to determine which PPE should be used, and that high standards of hand hygiene and PPE will protect healthcare staff and patients from HCAI. Isolation of patients with multidrug-resistant NP should be considered.

Influenza vaccination in healthcare workers in accordance with national guidance and pneumococcal immunisation in elderly and at-risk groups may reduce the incidence of NP.(1)

No studies have been carried out to assess the effect of routine screening for common pathogens causing NP. It would be beneficial to investigate whether routine screening has the effect of reducing the incidence of NP or enables targeting of treatment by early recognition of organisms, particularly to multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa.

Mechanical ventilation allows micro-organisms commonly found in the oropharynx and gut to move to the lungs, where they can lead to the development of pneumonia. It is therefore important to ensure that best standards of ventilator use are maintained to reduce the risk of VAP.

There is no evidence about the best sterilisation and maintenance procedures to use for ventilators, and hospitals should follow individual manufacturers’ guidelines. It is essential though that single-use devices are not re-used under any circumstances. The use of humidifiers has been investigated as a source of infection and the use of heated humidifiers (HHs) compared with heat and moisture exchangers (HMEs). Meta-analyses have concluded that HMEs are more effective than HHs in reducing the incidence of VAP and both BSAC and the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines(1,2) recommend that these be used unless there is a contraindication to their use.

Resuscitation equipment, anaesthetic machines and breathing equipment are all potential sources of infection if they become contaminated with bacteria, so  all such reusable equipment should be decontaminated according to the manufacturer’s instructions after use.

Nebulisers are also a potential source of infection and should be for single patient use only and cleaned between each use. There are reports of the use of spirometers being associated with NP and BSAC recommend that mouthpieces for spirometry equipment should be single use. All respiratory equipment where contamination by respiratory secretions is possible should be considered a potential infection risk for NP and precautions taken to reduce such risk.

Various patient procedures have the potential to increase the risk of NP and it is essential that healthcare staff be aware of these and adopt systems that reduce risk of infection developing. The UK DH has advocated the use of ‘care bundles’ to reduce the risk of NP and have specified a number of ‘high-impact interventions’ for ventilated patients,(8) including:

• Elevation of the head of the bed to 35–40 degrees
• Sedation holding
• Thromboprophylaxis
• Routine oral hygiene.

Use of nasotrachial intubation and re-intubation is associated with a higher incidence of VAP than oral intubation and BSAC recommends that oral intubation should be used in preference and that re-intubation should be avoided where possible.(1) A Cochrane review(10) found that results from 12 randomised controlled trials showed that use of non-invasive ventilation could decrease the incidence of pneumonia and should be used in preference in appropriate patients.

Enteral feeding is commonly required for patients on long-term ventilation. While there is a clear relationship between aspiration of gastric contents and the development of pneumonia, there is limited evidence that enteral feeding increases the risk. However, where enteral feeding is used in ventilated patients, care must be taken to ensure that the rate and volume of feeding is optimised to reduce the risk of aspiration. It has been suggested that different methods of delivery such as post-pyloric feeding and intermittent feeding might reduce the incidence of VAP, but there is no clear evidence to support this. Maintaining a patient in a semi-recumbent position during enteral feeding will also reduce the risk of aspiration.

The use of antacids and H2 antagonists for stress ulcer prophylaxis in ventilated patients increases the risk of VAP. Sucralfate might be a better alternative to reduce the risk of VAP, but has been associated with an increased risk of gastrointestinal bleeding and so should only be used in patients with a low-to-moderate risk of gastrointestinal bleeding.(1)

Physiotherapists and respiratory therapists have an important role to play in the prevention of respiratory complications in general in post-operative ventilated patients. Although there are no published data to show that they reduce the incidence of NP specifically, their input has been shown to reduce the duration of mechanical ventilation and help early mobilisation.

There is some evidence that transfusion of red cells, particularly stored red cells, is associated with an increased risk of NP and it is recommended(1)  that red cell transfusions should be avoided where possible, and, if used, should be with fresh red cells.

It is essential that good standards of cleanliness be maintained in hospitals to prevent HCAIs. The importance of this has been emphasised in the UK by the DH in their ‘Saving Lives’ initiative.(8)

There is an association between building works and the development of pulmonary aspergillus infections.(11) During building work it is therefore important that measures be taken to reduce dust levels in the environment and reduce exposure to fungal spores particularly where there are high-risk patients, such as those who are immunosuppressed.(1,11) Where the risk is considered to be particularly high, use of prophylactic antifungal agents can be considered.

Previously, NP was differentiated into HAP and VAP.(1,2) Another form of pneumonia that is classified as community-acquired but occurs in patients with strong links with the healthcare system, is termed healthcare-associated pneumonia or HCAP.(12) The ATS/IDSA guidelines state that: “HCAP is included in the spectrum of HAP and VAP, and patients with HCAP need therapy for MDR pathogens”.(2)

Viruses too may cause HAP. Herpes simplex virus (HSV) and cytomegalovirus (CMV) are the most frequent viruses in non-immunocompromised intensive care unit (ICU) patients that cause HAP.(16)

The BSAC guidelines for hospital-acquired pneumonia(1) state that VAP can be divided into early-onset and late-onset. In early-onset VAP, the pneumonia occurs within the first four days of mechanical ventilation, with the same organisms causing HAP. In late-onset VAP, that is, ≥five days of mechanical ventilation, organisms tend to be multidrug-resistant, and include MRSA and P. aeruginosa.

Diagnosis of nosocomial pneumonia is not straightforward. Best practice is a combination of clinical acumen, supported by microbiological evidence. Clinical signs and symptoms of HAP and VAP include at least two or more of the following signs and symptoms: fever (>38oC) or hypothermia (<35oC); leukocytosis; leucopoenia; increased immature neutrophils or purulent respiratory secretions; and the presence of a new or progressive radiographic infiltrate. Blood cultures can be helpful in diagnosing NP but are rarely positive, except for pneumococcal and S. aureus pneumonia.(1,15)

Empiric antimicrobial therapy is highly recommended in the treatment of NP. Delaying therapy until the pathogen is identified is not recommended. Relevant specimens (sputum or bronchoalveloar lavage) should be taken before the initiation of antimicrobial therapy. Monotherapy is as effective as combination therapy in early-onset HAP.(15,17)

The BSAC 2008 guidelines for HAP recommend co-amoxiclav or cefuroxime as first-line agent in early-onset HAP for patients without any additional risk-factors. Patients with early-onset who have had antibiotic exposure and other risk factors, would require piperacillin–tazobactam, or a third-generation cephalosporin or fluroquinolone.

For laboratory-confirmed pseudomonal nosocomial pneumonia, double antibiotic coverage with a high degree of anti-pseudomonal activity and a low resistance potential should be advocated. Combinations could include meropenem or doripenem with levofloxacin or aztreonam.

Alternatively, anti-pseudomonal penicillin (for example, piperacillin) in combination with levofloxacin, meropenem, aminoglycoside, or aztreonam might provide equal efficacy. NP is treated for 14 days and a clinical response should be evident during this time, if the appropriate treatment was initiated. Failure to improve would strongly indicate a non-infectious origin.(17)

A review by Joseph and colleagues in 2010(14) on VAP, reported that if the patient does not have any risk factors for multidrug-resistant pathogens, treatment is monotherapy with an agent such as ceftriaxone, fluroquinolone or ertapenem. However if risk factors for multidrug-resistant organisms are present, then cover must include anti-pseudomonal activity, for example, ceftazidime or meropenem or piperacillin–tazobactam + levofloxacin/ciprofloxacin or, instead of the fluroquinolone, an aminoglycoside can be used together with the anti-pseudomonal b-lactam. If risk factors are present for MRSA, linezolid or vancomycin must be added on to the anti-pseudomonal therapy.(2,14)

Telavancin (Vibativ®) is a novel lipoglycopeptide antibiotic, bactericidal against Gram-positive bacteria.(18,19) It has been recently licensed in the EU for nosocomial pneumonia in adults, including VAP, known or suspected to be caused by MRSA.(20)

Telavancin acts via a dual mechanism of action system that combines the inhibition of cell wall synthesis with the disruption of membrane barrier function. The ATTAIN1 and ATTAIN2 clinical studies were two identical, randomised, multinational, non-inferiority trials that investigated the efficacy of telavancin for HAP, HCAP and VAP, caused by Gram-positive bacteria. Patients were randomised to receive either vancomycin at a dose of 1g IV every 12 hours or telavancin 10mg/kg IV every 24 hours for a period of 7–21 days.(19)

Results from these trials concluded that telavancin achieved higher cure rates in patients with mono-microbial S. aureus infection and comparable cure rates with vancomycin, in patients with MRSA infection. In patients having a mixed Gram-positive/Gram-negative HAP, cure rates were higher in the vancomcyin-treated patients.

Certain coagulation tests, for example, activated partial thromboplastin time and International normalised ratio, are affected.(20) Telavancin does not require therapeutic drug monitoring unlike vancomycin; however, in patients with a creatinine clearance of 30–50ml/min, the dose must be reduced from 10mg/kg per day to 7.5mg/kg per day. The SPC states that the use of telavancin in ‘pre-existing acute renal failure and in patients with severe renal impairment is contraindicated’, although there are no drug–drug interactions with Vibativ. Patients may develop ototoxicity and

care is needed when patients have concomitant medications that might increase deafness and/or QT interval.(20)

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