Journal of Antimicrobial Chemotherapy

JAC Advance Access originally published online on April 29, 2008
Journal of Antimicrobial Chemotherapy 2008 62(1):5-34; doi:10.1093/jac/dkn162

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Reviews

Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy

R. G. Masterton^1,*, A. Galloway², G. French³, M. Street⁴, J. Armstrong⁵, E. Brown⁶, J. Cleverley⁷, P. Dilworth⁸, C. Fry⁹, A. D. Gascoigne¹⁰, Alan Knox¹¹, Dilip Nathwani¹², Robert Spencer¹³ and Mark Wilcox¹⁴

¹ Department of Microbiology, Crosshouse Hospital, Kilmarnock, UK ² Department of Microbiology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle-upon-Tyne, UK ³ Department of Infection, Guy's and St Thomas's NHS Foundation Trust and King's College, St Thomas' Hospital, London, UK ⁴ Department of Intensive Care, Royal Sussex County Hospital, Brighton, UK ⁵ Department of Public Health, North Durham Strategic Health Authority, Earls House, Durham, UK ⁶ Department of Microbiology, Frenchay Hospital, Bristol, UK ⁷ Department of Radiology, Royal Free Hospital, London, UK ⁸ Department of Thoracic Medicine, Royal Free Hospital, London, UK ⁹ Department of Health, London, UK ¹⁰ Royal Victoria Infirmary, Queen Victoria Road, Newcastle-upon-Tyne, UK ¹¹ Respiratory Medicine Unit, City Hospital, Nottingham, UK ¹² Infection Unit, Ninewells Hospital and Medical School, Dundee, UK ¹³ Health Protection Agency, Bristol Royal Infirmary, Marlborough St, Bristol, UK ¹⁴ University of Leeds, Leeds, UK

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^* Corresponding author. Tel: +44-1292-614510; Fax: +44-1292-288952; E-mail: robert.masterton{at}aaaht.scot.nhs.uk

	Abstract

Top Abstract Contents 1. Introduction 2. Prevention 3. Diagnosis 4. Treatment 5. Conclusions Addendum Funding Transparency declarations Comment on the editorial... References

 
These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.

Keywords: hospital-acquired pneumonia , healthcare-associated pneumonia , evidence-based guidelines , prevention , diagnosis , antimicrobial treatment

	Contents

Top Abstract Contents 1. Introduction 2. Prevention 3. Diagnosis 4. Treatment 5. Conclusions Addendum Funding Transparency declarations Comment on the editorial... References

 

1. Introduction

2. Prevention

 2.1. General issues for the prevention of HAP

   2.1.1. Role of staff education programmes

   2.1.2. Role of clinical guidelines or protocols

   2.1.3. Role of screening of patients or their environment to prevent HAP

   2.1.4. Immunization to prevent HAP

   2.1.5. Importance of hand hygiene in preventing HAP

   2.1.6. Role of personal protective equipment

 2.2. Infection control issues related to the use of equipment—best methods of sterilization or disinfection of equipment and maintenance of instruments

   2.2.1. Mechanical ventilators

   2.2.2. Ventilator circuits

   2.2.3. Heated humidifiers and HMEs

   2.2.4. Frequency of change of humidifiers

   2.2.5. Nebulizers

   2.2.6. Filters

   2.2.7. Suction equipment

   2.2.8. Resuscitation equipment

   2.2.9. Anaesthetic machines and breathing equipment

   2.2.10. Pulmonary function testing equipment

 2.3. Patient procedures

   2.3.1. Closed versus open suctioning

   2.3.2. Use of non-invasive positive pressure ventilation

   2.3.3. Method of ET intubation

   2.3.4. Use of enteral feeding

   2.3.5. Different methods of enteral feeding

   2.3.6. Prevention of aspiration

   2.3.7. Use of sucralfate and stress ulcer prophylaxis

   2.3.8. Effect of breathing exercises

   2.3.9. Role of physiotherapists and respiratory therapists

   2.3.10. Use of incentive spirometry

   2.3.11. Positional strategies

   2.3.12. Use of kinetic beds (oscillatory therapy)

   2.3.13. Use of red cell transfusions

 2.4. Environmental issues

   2.4.1. Methods to reduce transmission of Aspergillus during building work

   2.4.2. Use of prophylactic antifungal agents during building work

   2.4.3. Legionella control

   2.4.4. Cleanliness of the environment

3. Diagnosis

 3.1. General issues in the diagnosis of HAP

   3.1.1. Definitions of HAP

   3.1.2. Issues in assessing the literature on diagnosis of HAP

   3.1.3. An assessment of lung histology and culture as a reference standard for the diagnosis of HAP

 3.2. The clinical diagnosis of HAP

   3.2.1. Clinical diagnostic criteria

   3.2.2. The clinical pulmonary infection score

 3.3. The radiological diagnosis of HAP

 3.4. The microbiological diagnosis of HAP

   3.4.1. The microorganisms of HAP

   3.4.2. The contribution of blood cultures in the diagnosis of HAP

   3.4.3. An assessment of microbiological sampling methods

      3.4.3.1. Bronchoscopy-directed PSB and BAL

      3.4.3.2. Blind PSB and BAL

      3.4.3.3. Endotracheal aspirates (EAs)

      3.4.3.4. The role of quantitative microbiology in the diagnosis of HAP/VAP

      3.4.3.5. Quantification of intracellular organisms in the diagnosis of HAP

4. Treatment

 4.1. The prevention of HAP using antimicrobials

   4.1.1. The role of selective decontamination of the digestive tract (SDD)

   4.1.2. An assessment of the impact of SDD

   4.1.3. The choice of antimicrobial treatments for SDD

   4.1.4. The relationship of resistance development to SDD

   4.1.5. The cost-effectiveness of SDD

   4.1.6. Prevention of HAP using parenteral antibiotic prophylaxis

 4.2. Treatment with antimicrobials in the management of HAP

   4.2.1. Selection of antimicrobials in the management of HAP

 4.3. The role of invasive sampling and quantitative microbiology of respiratory secretions in directing antimicrobial therapy in HAP/VAP

   4.3.1. Non-randomized studies

   4.3.2. Randomized studies

   4.3.3. The effect of reporting antimicrobial susceptibilities of organisms cultured from respiratory tract secretions

   4.3.4. The effect of timely and appropriate antimicrobial therapy in HAP/VAP

   4.3.5. The duration of antimicrobial treatment in the management of HAP

   4.3.6. Definitive treatment when the causative organism is P. aeruginosa

   4.3.7. Definitive treatment when the causative organism is MRSA

   4.3.8. The role of pharmacokinetic (PK) and pharmacodynamic (PD) antibiotic features as a guide to treatment selection in HAP

   4.3.9. The choice between monotherapy and combination therapy in the treatment of HAP

   4.3.10. Airway administration of antimicrobials in the management of HAP

   4.3.11. Switching from intravenous to oral antimicrobial therapy in the management of HAP

 4.4. Therapeutic modalities other than antimicrobials in the management of HAP

   4.4.1. Activated protein C

   4.4.2. Granulocyte-colony stimulating factor (G-CSF)

   4.4.3. Physiotherapy

   4.4.4. Steroids

 4.5. The use of clinical protocols for treating HAP

   4.5.1. Clinical outcomes

   4.5.2. Cost-effectiveness

5. Conclusions

	1. Introduction

Top Abstract Contents 1. Introduction 2. Prevention 3. Diagnosis 4. Treatment 5. Conclusions Addendum Funding Transparency declarations Comment on the editorial... References

 
Hospital-acquired pneumonia (HAP) is a respiratory infection developing more than 48 h after hospital admission. HAP affects 0.5% to 1.0% of inpatients and is the most common healthcare-associated infection (HCAI) contributing to death.¹ It is estimated to increase hospital stay by 7–9 days.² In a proportion of patients, HAP is associated with mechanical ventilation, in which case it is termed ventilator-associated pneumonia (VAP). In patients with VAP, there is a 24% to 50% mortality rate, which increases to 76% if infection is caused by multidrug-resistant pathogens.³ VAP accounts for up to 25% of all intensive care unit (ICU) infections with the risk being highest during early ICU stay when it is estimated to be 3%/day during the first 5 days of ventilation, followed by 2%/day up to day 10 of ventilation and thereafter 1%/day.⁴ These features of high incidence with significant morbidity and mortality consequences have driven considerable recent interest in the creation of HAP guidelines. Prevention of HAP is therefore not only desirable but also essential for providing cost-effective healthcare. The Department of Health (DH) in its ‘Saving Lives’ initiative has seven high-impact interventions that are part of the programme to reduce HCAI and one of these relates to the care of the ventilated patient.⁵

Although guidelines for HAP in the UK have not been previously published, a total of 10 international HAP guidelines have been released over the last 7 years.⁶ Of these, only one both used a systematic review of the literature approach and covered each of prevention, diagnosis and treatement.⁷ These American Thoracic Society guidelines, however, used a semi-qualitative approach to assessment and did not weigh fully both the strength and the quality of the evidence. Over half of the available guidelines are based on expert opinion and cover only one or two of the three relevant areas of consideration. Recently, a number of guidelines have been published relating to prevention of both VAP^7,8 and the combination of non-ventilator-associated HAP and VAP.^6,9,10 These have been produced in different ways with none employing a full systematic review approach that fully meets an appraised quality methodology.

The guidelines presented here were developed by a Working Party of the British Society of Antimicrobial Chemotherapy (BSAC). The overall guideline is divided into three sections dealing with prevention, diagnosis and treatment. In producing the guidelines, the Working Party adopted a systematic review approach using a formally evaluated quality assessment mechanism. The tool chosen was the guideline development process produced by the Scottish Intercollegiate Guideline Network (SIGN).¹¹ This methodology includes an explicit description of the level, definitions and volume of evidence, which is reviewed by a multidisciplinary development team. The product grades the recommendations according to the quality of supporting evidence with the output being subject to a final expert peer assessment prior to release (Table 1). The SIGN tool has been assessed against and meets the guideline quality requirements of the Appraisal of Guidelines Research and Evaluation instrument.¹¹

View this table: [in this window] [in a new window]   Table 1. Grades of recommendation11

 
Literature searches were undertaken on Medline, Embase, the Cochrane Database and professional and journal Internet sites. A definitive search string was developed for each question and if necessary for each subquestion. Strings were developed for Medline searches and amended accordingly for Embase searches. The searches were initially run in August 2002 with a final check in July 2005. The total number of search strings deployed was 31 for prevention, 7 for diagnosis and 15 for treatment. These yielded, respectively, 971, 1753 and 3868 citations for review with 350, 85 and 308 articles proceeding to formal full assessment. The scope of the guideline generally excludes oral antiseptic treatments, severely immunocompromised patients, children <16 years old and patients with cystic fibrosis (CF). Consultation with stakeholders took place over an 8 week period through open access on the BSAC web site and through invited comments from relevant professional bodies and learned societies.

The guideline is divided into three main sections (prevention, diagnosis and treatment) to cover all relevant issues within the scope of the project. Prevention was divided into four sections to include the different modifiable aspects of patient care that can be used to help prevent against HAP. These include:

• General issues—staff education; use of clinical guidelines or protocols; screening patients and their environment, immunization strategies; hand hygiene and the use of personal protective equipment.
  
• Use of equipment—maintenance and sterilization or disinfection.
  
• Patient procedures—suctioning; non-invasive ventilation (NIV); method of endotracheal (ET) intubation; enteral feeding; prevention of aspiration; stress ulcer prophylaxis; breathing exercises, physiotherapy, incentive spirometry, positional strategies, the use of kinetic beds; use of red cell transfusions.
  
• Environmental issues—methods to reduce transmission of Aspergillus during building work; the use of antifungal prophylaxis; control of Legionella and cleanliness of the environment.
  

The work on diagnosis is divided into three sections that cover the main diagnostic approaches for HAP: clinical assessment, radiological investigation and microbiological investigation. Similarly, treatment is divided into five sections to include the different aspects of patient care. These cover both the use of antimicrobials in prevention and in treatment, the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy, the use of adjunctive therapies and the application of clinical protocols.

	2. Prevention

Top Abstract Contents 1. Introduction 2. Prevention 3. Diagnosis 4. Treatment 5. Conclusions Addendum Funding Transparency declarations Comment on the editorial... References

 
2.1 General issues for the prevention of HAP

2.1.1 Role of staff education programmes. Only a limited number of studies addressed this issue. These included four cohort studies^12–15 and one case–control study.¹⁶ Data from two cohort studies^13,14 showed that education programmes are effective in reducing the incidence of VAP by 51% and 56%, respectively. A cohort study¹⁵ also showed that introducing protocols and education was effective in reducing VAP by 50%. One other cohort study¹² and a case–control study¹⁶ demonstrated that as part of a broad intervention, programmed education can be successful in controlling staff-to-staff or staff-to-patient outbreaks of primary respiratory pathogens, e.g. pertussis and respiratory syncytial virus. A cohort study showed that when a higher proportion of care was provided by qualified registered nursing staff, there was a lower incidence of HAP.¹⁷ Studies therefore consistently provide evidence that staff education programmes both in themselves and as part of an overall infection control programme reduce the incidence of VAP.

We recommend that hospital education programmes as part of an overall infection control strategy should form part of the risk reduction measures for HAP. Recommendation Grade B

Appropriate levels of experienced nursing staff should be involved in patient care to prevent HAP and education of staff on the measures that should be taken to prevent HAP should form part of their induction and continuing professional development. Recommendation Grade GPP

2.1.2 Role of clinical guidelines or protocols. Most published guidelines relate specifically to prevention of VAP rather than HAP. Two randomized controlled trials (RCTs) showed that care protocols in ICUs decrease the incidence of VAP, particularly in trauma patients.^18,19 Two other RCTs, specifically on the use of weaning protocols for ventilated patients on ICU, found that the use of protocols by nurses and respiratory therapists resulted in reduced duration of mechanical ventilation, improved clinical outcome and reduced costs.^20,21 Also the use of protocols for reducing sedation has been reported as being effective in shortening the duration of ventilation and ICU stay.^22,23 Although there were few papers, those identified provided good evidence that clinical guidelines reduced the incidence of VAP.^18–24 As there is no direct evidence that guidelines affect the incidence of HAP outside of ICUs, no recommendation can be made in respect of the value of clinical guideline implementation in this scenario.

We recommend that care protocols and guidelines for weaning and sedation should be developed and actively followed in the critical care setting to reduce the incidence of VAP. Recommendation Grade A

In order to reduce the incidence of HAP, adherence to clinical guidelines should be monitored to ensure compliance. Recommendation Grade GPP

2.1.3 Role of screening of patients or their environment to prevent HAP. There are no studies that examined the benefit of routine surveillance for HAP organisms in patients or their environment, in preventing HAP, and so no recommendation can be made on this topic. Future research is recommended in order to assess whether taking routine screening samples from patients helps to reduce the incidence of HAP or assists in targeting treatment through the early recognition of organisms causing HAP. Work is also needed to assess whether routine screening of the environment for organisms causing HAP reduces the incidence of HAP due to multiresistant Gram-negative bacteria, e.g. Pseudomonas aeruginosa or Acinetobacter spp.

We recommend that limited and targeted surveillance of organisms causing pneumonia in ICU patients should be carried out to identify cross-infection or outbreaks and other infection control problems, e.g. a single case of hospital- acquired Legionella infection.²⁵ This type of surveillance is also helpful in providing feedback to assist clinicians in empirical antibiotic selection and on the incidence and susceptibility of organisms causing VAP.²⁶ Recommendation Grade GPP

2.1.4 Immunization to prevent HAP. Immunization relevant to the prevention of HAP includes, particularly, influenza and pneumococcal vaccines. Most published papers cover influenza (including influenza pneumonia), the elderly and healthcare workers and mainly relate to outbreaks in nursing homes. A meta-analysis²⁷ reviewing this area included 20 observational studies of HAP in the elderly and there are also cohort studies^28,29 and three RCTs.^30–32

Existing UK guidance³³ already highlights the importance of immunization against influenza and pneumococcal disease for high-risk adult and paediatric patients. Immunization of healthcare workers involved with at-risk patients is also recommended. However, there is no direct evidence that influenza immunization of healthcare workers or patients will directly reduce the incidence of HAP, although one study²⁸ found evidence to suggest that influenza immunization prevents pneumonia in elderly patients. The same study reported that a failure to immunize healthcare workers against influenza was associated with an increased mortality from ‘influenza like illness’ in elderly patients. There is also no direct evidence that pneumococcal immunization of healthcare workers or patients reduces the incidence of HAP.

We recommend that the use of influenza immunization in healthcare workers and patients and pneumococcal immunization in elderly and at-risk groups should be encouraged. Recommendation Grade C

In line with the recommendations of the Joint Committee on Vaccination and Immunization,³³ influenza immunizations should be actively encouraged in at-risk patients and healthcare workers. Recommendation Grade GPP

2.1.5 Importance of hand hygiene in preventing HAP. A number of studies have assessed the effects of hand hygiene on staff-to-patient and staff-to-equipment transfer of bacteria. There is good evidence that an inverse relationship exists between high standards of hand hygiene and the incidence of HCAI, but there is no good evidence of a direct relationship with the prevention of HAP.^34–38 Hand hygiene is effective in reducing HCAI and the epic Project evidence-based guidelines for the prevention of HCAI recommend implementation of a hand hygiene policy.³⁹

We recommend that hand hygiene guidelines are available as part of evidence-based processes for preventing HCAI and that these should be followed. Hand hygiene practices should be incorporated into clinical guidelines for the prevention of HAP and performance audits of these should be carried out to demonstrate and maintain high levels of practice. Recommendation Grade GPP

With a view to reducing the incidence of HAP, staff hand hygiene should form part of routine care with hands being decontaminated immediately before and after every episode of direct patient contact and after any activity or contact that potentially results in hands becoming contaminated. Hand decontamination after glove removal should be performed. Recommendation Grade GPP

2.1.6 Role of personal protective equipment. There is an absence of evidence to address this issue. The studies available relate to HCAI and not directly to HAP. There are data showing that the appropriate use of Personal Protective Equipment (PPE) prevents the spread of microorganisms and HCAI,^39,40 which might potentially reduce the incidence of HAP. It is essential that the choice of PPE is appropriate to the risk of infection, e.g. simple surgical masks are inadequate in protecting against tuberculosis and some respiratory viruses.⁴¹ Appropriate equipment needs to be readily available and the necessary training given in its use. National health and safety at work requirements such as PPE regulations^42,43 and Control of Substances Hazardous to Health regulations⁴⁴ should be followed.

We recommend that the role of PPE in the prevention of HAP should involve local risk assessment with reference to national health and safety at work requirements, e.g. PPE Regulations^42,43 and local infection control advice. Recommendation Grade D

We recommend high standards of hygiene including hand hygiene and PPE, as these will protect healthcare workers and patients against HCAI from microorganisms including influenza and other viral respiratory pathogens. Recommendation Grade GPP

Gloves should be put on immediately before an episode of patient contact or treatment and removed as soon as the activity is completed and should be changed between caring for different patients or between different care/treatment activities for the same patient. Recommendation Grade GPP

Care needs to be taken in the use of PPE to prevent spreading infection between patients, e.g. gloves can contaminate hands if not removed correctly and hence the importance of hand decontamination after glove removal.⁴⁵ Recommendation Grade GPP

Personal respiratory protection is required in certain respiratory infections, e.g. multidrug-resistant tuberculosis, human coronavirus etc. or when patients who are severely immunocompromised are exposed to infection [e.g. not in a high efficiency particulate air (HEPA)-filtered environment]. In these instances, specialized respiratory protective equipment should be worn. Recommendation Grade GPP

National guidelines should be followed with regard to protection of staff against highly communicable infections, e.g. human coronavirus. Recommendation Grade GPP

Isolation of patients with multidrug-resistant infections including pneumonia should be performed alongside the use of PPE to prevent the spread of infection. Recommendation Grade GPP

2.2 Infection control issues related to the use of equipment—best methods of sterilization or disinfection of equipment and maintenance of instruments

2.2.1 Mechanical ventilators. In respect of HAP risk reduction, there is an absence of evidence about the best sterilization/disinfection/maintenance procedures for mechanical ventilators. The reuse of ‘single-use’ devices can affect their safety, performance and effectiveness, exposing patients and staff to unnecessary risk. It also carries legal implications as anyone who reprocesses or reuses a device intended by the manufacturer for use on a single occasion bears full responsibility for that item's safety and effectiveness, including to any organization to which the equipment is transferred.⁴⁶

We recommend that, in line with the Medical Device Agency guidance⁴⁶ on single-use medical devices, items designated for ‘single-use’ must not be reused under any circumstances. Recommendation Grade GPP

Equipment should be sterilized, disinfected and maintained according to the manufacturer's instructions. Recommendation Grade GPP

2.2.2 Ventilator circuits. A systematic review which included four RCTs and seven observational studies found that changing the ventilator circuit less frequently than every 24 h reduced the risk of VAP.⁴⁷ Another systematic review⁴⁸ assessed three RCTs where one⁴⁹ was considered a higher quality trial than the other two.^50,51 The review concluded that the frequency of ventilator circuit changes does not influence the incidence of VAP; that less frequent changes of ventilator circuits are not associated with harm and that more frequent changes are associated with increased cost. A further RCT found no difference in the rate of VAP in patients with ventilator circuits containing heat moisture exchangers (HMEs) where 48 h circuit changes were compared with no planned change.⁵² These studies were all conducted in ventilated patients where circuits were changed if there were signs of visible contamination or damage. Further research regarding safety and infection control criteria is required to determine the maximum length of time between ventilator tubing changes.

Provided they are otherwise changed if they become soiled or damaged, we recommend that ventilator circuits need not be changed before 7 days. Recommendation Grade A

New ventilator circuit tubing should be provided for each patient. Recommendation Grade B

In order to prevent contamination of the healthcare worker, facial protection should be used alongside PPE when closed breathing circuits are disconnected. This is especially important when dealing with patients with highly communicable infections, e.g. human coronavirus. Recommendation Grade GPP

To prevent VAP, breathing circuit condensate should be managed so that it does not drain towards the patient and it should be periodically drained and discarded.^7,53 Recommendation Grade GPP

2.2.3 Heated humidifiers and HMEs. There are two meta-analyses^47,54 and a systematic review⁴⁸ which have compared the use of heat humidifiers (HHs) and HMEs. One meta-analysis⁵⁴ covered all eight RCTs cited by the other papers that have examined the use of different humidifier types and their effect on the incidence of VAP.^55–62 This meta-analysis concluded that in patients ventilated for >7 days, the use of HMEs is associated with a statistically significant reduction in the incidence of VAP when compared with HHs. Whereas concern was expressed in the earlier systematic review⁴⁸ about ET tube obstruction associated with HME use, this has not been confirmed in recent studies evaluating newer HMEs.⁶³ Two RCTs^57,62 have shown reduced costs associated with the use of HMEs compared with HHs.

Provided there are no contraindications to their use (e.g. patients at risk of airways obstruction), we recommend that HMEs rather than HHs are used, as HMEs are more effective in reducing the incidence of VAP. Recommendation Grade A

When HMEs are used, the type chosen should be one that has adequate moisture output to minimize the risk of airway obstruction. The benefit of use of HMEs versus HHs should be established for each patient and this decision should not be based solely on infection control considerations. Recommendation Grade GPP

National guidelines should be followed in respect of the use of humidifiers and HMEs for the management of patients with highly communicable infections, e.g. human coronavirus. Recommendation Grade GPP

2.2.4 Frequency of change of humidifiers. A systematic review⁴⁷ and three RCTs address this issue^64–66 with two of the latter^64,65 specifically evaluating the effect on VAP of a reduced frequency of change of the humidifier. One study that looked at efficacy and safety by studying three different types of HMEs reported that not all HMEs performed equally with only some brands able to be used for 48 h without change.⁶⁴ It has also been reported that changing HMEs after 3 days does not diminish the efficiency of the equipment or increase the incidence of VAP.⁶⁵ From these studies, there is no evidence that more frequent changing of HHs and HMEs than manufacturers recommend reduces the risk of HAP.

We recommend that where HHs and HMEs are used (except with high minute volume) these should not be changed routinely and manufacturer's guidance should be followed. Recommendation Grade A

The technical performance of HMEs for more than 48 h should be monitored, especially in patients with chronic obstructive pulmonary disease (COPD), and if there is evidence or suspicion of contamination, the humidifier should be changed. Recommendation Grade GPP

2.2.5 Nebulizers. Nebulizers are used both in the ICU and wards and departments to deliver bronchodilators and other drugs. Three diagnostic studies have reported that nebulizers can become contaminated and act as a source of respiratory tract infection.^67–69

We recommend that nebulizers should be single patient use and need to be disinfected and cleaned with sterile water between each use. Recommendation Grade D

Nebulizers used as part of the ventilator circuit should be single use only and national guidelines should be followed with regard to the use and cleaning of nebulizers. Recommendation Grade GPP

2.2.6 Filters. There are reports in the literature that provide evidence to support the use of filters to protect circuit systems from bacterial contamination,^68,70,71 but there is no evidence which establishes that the use of filters specifically protects against HAP.

We recommend that appropriate filters are used to protect mechanical ventilator circuits from bacterial contamination. Recommendation Grade C

National guidelines should be followed with regard to the use of expiratory filters for patients suffering from highly communicable infections, e.g. human coronavirus, and who require mechanical ventilation. Recommendation Grade GPP

2.2.7 Suction equipment. Suctioning of patients on intensive care is essential to prevent pooling of respiratory secretions. A systematic review⁴⁷ and three other studies^72–74 have examined the effect of daily changes of in-line suctioning equipment and found that when compared with less frequent changes, this had no effect on the incidence of VAP. Whereas there is, therefore, no evidence that changing closed suction equipment daily reduces the risk of VAP, the maximum duration that a closed suction catheter can be used against safety and infection control considerations is not known.

We recommend that daily change of suction equipment is not required. Recommendation Grade A

Suction equipment may be changed weekly unless it becomes contaminated or damaged, in which case it should be changed immediately. Recommendation Grade GPP

2.2.8 Resuscitation equipment. Four studies on use of bag-valve mask ventilation (manual ventilation/‘Re-breathe’) bags have reported that such resuscitation equipment can act as a source of HAP if it becomes bacterially contaminated.^75–78

We recommend that in order to minimize the risk of HAP multiuse, bag-valve mask ventilation (manual ventilation/‘Re-breathe’) bags should be decontaminated according to the manufacturer's guidelines between each patient use. Recommendation Grade C

All reusable resuscitation equipment should be appropriately decontaminated according to the manufacturer's recommendations after use and if possible single patient use equipment (e.g. Ambu bag) should be employed. Recommendation grade GPP

2.2.9 Anaesthetic machines and breathing equipment. A diagnostic study suggested that basic hygienic management of anaesthetic equipment was adequate to prevent cross-infection.⁷⁹ Studies are required to establish the best sterilization or disinfection and maintenance methods to reduce the risk of HAP from anaesthetic machines and breathing systems.

We recommend that to reduce the risk of HAP, basic hygienic measures should be adopted for anaesthetic equipment. Recommendation Grade D

Provided filters are in place to protect the equipment, anaesthetic equipment should be decontaminated according to the manufacturer's instructions. Recommendation Grade GPP

Changing HMEs and anaesthetic machine valve between patients and weekly circuit changes should be adequate to prevent infection from anaesthetic machines. Recommendation Grade GPP

If anaesthetic equipment is used on a known infected patient, tubing and filters should be changed before the next patient use. Recommendation Grade GPP

2.2.10 Pulmonary function testing equipment. There are reports of the use of spirometers being associated with HAP caused by Acinetobacter spp.^80,81 One study reported that the mouthpieces of spirometry tubing can become contaminated with bacteria during use and recommended that to prevent the acquisition of microorganisms causing HAP they should not be shared between patients.⁸²

We recommend that spirometry mouthpieces should be single use only. Recommendation Grade C

All respiratory equipment, where contamination by respiratory secretions is possible, should be viewed as a potential infection risk for HAP and therefore precautions should be taken to reduce such risks. Recommendation grade GPP

2.3 Patient procedures

2.3.1 Closed versus open suctioning. Several studies have assessed the effect of closed versus open suctioning on VAP, but their results are not consistent. A systematic review⁴⁸ considered evidence from four RCTs^83–86 and concluded that the type of suctioning system had no effect on the incidence of VAP. Two further RCTs confirmed these findings.^87,88 However, one RCT reported a 3.5 times greater risk of VAP in patients receiving open versus closed suctioning.⁸⁴ Most studies, therefore, show that closed as opposed to open suctioning of respiratory tract secretions does not affect the risk of VAP and there is no evidence that closed suctioning increases the risk of VAP.

No recommendation can be made on the use of closed suctioning to reduce the risk of HAP to patients and we recommend that closed or open suctioning systems can be used without affecting the risk of VAP. Recommendation Grade B

From a safety perspective, closed suctioning of respiratory tract secretions is of value in reducing the aerosolization of respiratory tract secretions and protection of healthcare workers. The number of disconnections of suction equipment should be minimized to reduce the risk of exposure to staff to potentially infected secretions. Recommendation Grade GPP

2.3.2 Use of non-invasive positive pressure ventilation. NIV involves providing respiratory support to patients without the need for intubation. There is evidence that in selected patients NIV reduces the risk of HAP. A Cochrane systematic review⁸⁹ included five RCTs and found that in patients with COPD, NIV reduced the risk of HAP. Although the indications for this procedure are relatively narrow, the numbers of patients to whom they apply are large.

We recommend that to reduce the risk of HAP, NIV rather than mechanical ventilation should be used in appropriate patients. Recommendation Grade A

2.3.3 Method of ET intubation. One RCT⁹⁰ specifically addressed the issue of oral versus nasotracheal intubation with regards to the development of VAP, whereas this and four other RCTs^91–94 also assessed the development of maxillary sinusitis. All these demonstrated an association between nasotracheal intubation and maxillary sinusitis. Another study showed that re-intubation is associated with an increased incidence of VAP.⁹⁵

We recommend that, where possible, oral ET intubation should be used in preference to nasotracheal intubation and that re-intubation should be avoided if possible. Recommendation Grade C

2.3.4 Use of enteral feeding. Enteral feeding is used to prevent the development of a catabolic state in patients requiring long-term ventilation. A cohort study⁹⁶ of ventilated patients showed a relationship between enteral feeding and aspiration, but there is limited other evidence to support this. There is also an absence of evidence that the incidence of HAP in ventilated patients is reduced by taking measures to reduce aspiration associated with enteral feeding. In view of these findings, no recommendation can be made about the use of enteral feeding to prevent HAP.

We recommend that in ventilated patients, the rate and volume of enteral feeding should be adjusted to avoid gastric distension and so reduce the risk of aspiration. Recommendation Grade GPP

2.3.5 Different methods of enteral feeding. There are a number of methods of providing enteral feeding and these were assessed in a systematic review.⁹ Four RCTs that evaluated different methods of enteral feeding, which included intermittent feeding,⁹⁷ the use of metoclopramide and acidification of feeding, were reviewed. No difference in the incidence of VAP or mortality was found with any of these strategies. A meta-analysis⁹⁸ of seven RCTs looked specifically at post-pyloric feeding and reported that compared with gastric feeding this was associated with a significant reduction in VAP. It was suggested that further studies are warranted. A second meta-analysis⁹⁹ that included nine RCTs compared gastric versus post-pyloric feeding and found that there was no significant difference in the incidence of VAP in each group. Further research is required to study the effect of different modes of feeding on the incidence of HAP.

We recommend that as there is no clear evidence that intermittent feeding, small intestine feeding, the use of metoclopramide or acidification of feeding prevent VAP, the decision on the method of enteral feeding to be used for critically ill patients should be made locally by each unit and on an individual patient basis. Recommendation Grade A

When enteral feeding is used, the method of delivery should be optimized for each patient. Recommendation Grade GPP

2.3.6 Prevention of aspiration. The relationship between aspiration of gastric contents and pneumonia/pneumonitis is well known. Although there is an absence of evidence that prevention of aspiration associated with ET intubation reduces the incidence of HAP, a cohort study⁴ reported that witnessed aspiration was associated with an increased risk of VAP. A meta-analysis¹⁰⁰ found that establishing subglottic drainage was effective in preventing early-onset VAP in patients expected to remain ventilated for more than 72 h.

We recommend that to prevent VAP, measures should be taken to reduce the risk of aspiration and this should include subglottic drainage and positioning. Recommendation Grade B

Attention needs to be paid to the ET cuff pressure to avoid aspiration and prevent tracheal damage (>25 and < 30 cm water).¹⁰¹ Recommendation Grade GPP

2.3.7 Use of sucralfate and stress ulcer prophylaxis. There is clear evidence that a reduction of gastric acid by various methods, including antacids and H2 antagonists used for stress ulcer prophylaxis in ICU patients on ventilation, increases the risk of VAP. However, the literature is not consistent with regard to the use of sucralfate in this context. A systematic review⁹ that considered seven meta-analyses found evidence in four of these^102–105 that sucralfate when compared with H2 antagonists significantly reduced the incidence of VAP. The three other meta-analyses did not show a statistically significant reduction in VAP with the use of sucralfate, but did show a trend to this effect.^106–108 A large RCT¹⁰⁹ found that in mechanically ventilated patients, sucralfate therapy was associated with a statistically significantly increased risk of clinically important gastrointestinal bleeding compared with H2 antagonists. There is, therefore, evidence that the use of sucralfate is associated with a reduced risk of VAP when compared with the use of other agents that raise gastric alkalinity in ventilated patients, but sucralfate therapy has been associated with an increased risk of clinically important gastrointestinal bleeding when compared with ranitidine.

We recommend that whenever clinically appropriate, stress ulcer prophylaxis should be avoided in order to help preserve gastric function. Recommendation Grade A

We recommend that where stress ulcer prophylaxis is indicated, sucralfate is to be preferred in order to reduce the risk of VAP, but sucralfate should only be used in patients with low to moderate risk of gastrointestinal bleeding. Recommendation Grade A

2.3.8 Effect of breathing exercises. There is an absence of evidence that instructing patients to cough or take deep breaths reduces the incidence of HAP. Two cohort studies^110,111 and an RCT¹¹² did not specifically look at HAP but considered pulmonary complications in general. Another study¹¹³ found that the most effective regimen of prophylaxis against pulmonary complications for low-risk patients after abdominal surgery was deep breathing.

We recommend that coughing and early mobilization during the post-operative recovery period should be encouraged in all patients in order to reduce the risk of pulmonary complications. Recommendation Grade GPP

2.3.9 Role of physiotherapists and respiratory therapists. We found no data on the role of physiotherapists and respiratory therapists in reducing the incidence of HAP in general. However, one study¹¹⁴ showed the benefit of chest physiotherapy in preventing VAP, whereas an RCT¹¹⁵ demonstrated that physiotherapy with incentive spirometry reduced respiratory complications in high-risk surgical patients. A systematic review¹¹⁶ assessed the role of respiratory therapists and reported five RCTs, which showed that respiratory therapists were effective in implementing respiratory care protocols to wean patients from mechanical ventilation and in appropriately allocating respiratory care in adult non-ICU patients but did not relate either of these features to HAP prevention. Therefore, there is evidence that respiratory therapists, by following weaning protocols, both reduce the duration of mechanical ventilation and ICU stay and improve outcome. Also, physiotherapy with incentive spirometry in high-risk abdominal surgery patients can reduce respiratory complications, including pneumonia. Further research is required to establish the role of physiotherapy in the prevention and management of HAP.

We recommend that physiotherapists and respiratory therapists have a role in preventing respiratory complications in post-operative ventilated patients. Recommendation Grade A

Physiotherapists and respiratory therapists have a holistic role in the pre- and post-operative care of patients, especially in high-risk patients, where risk assessment indicates this may be of value. Recommendation Grade GPP

2.3.10 Use of incentive spirometry. There is some evidence that the use of incentive spirometry in post-operative, high-risk surgical patients may be beneficial, although this is poor, with only one RCT.¹¹⁵ There is an absence of evidence that incentive spirometry has any impact on reducing the risk of HAP in low-risk surgical patients after abdominal surgery. Further research is required to assess the effects of incentive spirometry in patients requiring surgery.

We recommend that incentive spirometry has no role to play in prevention of HAP in the low-risk (ASA grade 1 or 2) surgical patient, including patients who had no pre-existing pulmonary complications, and that it should be used in high-risk patients to prevent respiratory complications. Recommendation Grade D

2.3.11 Positional strategies. Several studies have looked at the use of semi-recumbent, prone and supine positioning in relation to the risk of HAP. An RCT¹¹⁷ found that the use of semi-recumbent positioning may prevent VAP and also reported that supine body positioning and enteral feeding were independent risk factors for the development of nosocomial pneumonia (NP). However, an earlier study¹¹⁸ with a smaller number of patients concluded that the semi-recumbent positioning did not prevent VAP. Another RCT¹¹⁹ looked at the effect of prone positioning on patients with acute respiratory failure and found that there was no general benefit from using prone positioning and that there were concerns about safety. However, a cohort study¹²⁰ showed that patients nursed in supine head positioning during the first 24 h of ventilation had an increased risk of VAP. A further study¹²¹ reported a significant increase in VAP in patients transported out of ICU for interventions, which was most likely related to positioning.

We recommend that a positional strategy should be adopted to prevent VAP. If a patient does not require to be supine, and provided there are no contraindications, consideration should be given to using the semi-recumbent position (30–45°) as a strategy to prevent VAP. Recommendation Grade B

Consideration should be given to adopting a positional strategy to prevent HAP in non-ventilated patients. Recommendation Grade GPP

Patients on ventilation being transported out of ICU should if possible be maintained in the semi-recumbent position. Recommendation Grade GPP

In order to prevent aspiration, patients should be kept in a semi-recumbent position during enteral feeding. GPP

2.3.12 Use of kinetic beds (oscillatory therapy). There is a limited amount of evidence on the use of kinetic beds to prevent HAP. A meta-analysis,¹²² which included six studies, and a systematic review⁴⁸ covering eight RCTs have reviewed the use of kinetic (oscillating) beds. Their conclusion was that although these may have an impact on reducing complications associated with intensive care, it is inconclusive whether they affect the development of HAP. At present no recommendation for use of kinetic therapy to prevent HAP can be made from the evidence and further research is required to assess the value of kinetic therapy in the prevention of HAP in different patient populations and especially in ICUs.

2.3.13 Use of red cell transfusions. The use of transfusions has been particularly studied in post-operative patients and those receiving intensive care. One study¹²³ demonstrated that transfusion of >4 U or red cell concentrate was associated with an increased risk of HAP in cardiac surgery patients, whereas another cohort study showed that the use of stored red blood cells increased the risk of HAP.¹²⁴ In contradistinction, a study¹²⁵ reported that a restrictive transfusion policy in ICU patients is at least as effective as a liberal policy with regard to the effect on mortality and multiorgan failure. Finally, a cohort study reported that leucocyte-depleted blood was better than buffy-coat reduced blood in preventing pneumonia in patients undergoing colorectal surgery.¹²⁶ There is, therefore, some evidence that the use of red cell transfusions increases the risk of HAP and the evidence available is particularly applicable in cardiac and colorectal surgery. Further research needs to be carried out to establish the effect of red cell transfusions on the development of HAP in other patient groups.

We recommend that to prevent HAP, red cell transfusions should be avoided if possible and if used should be with fresh red cells. Recommendation Grade C

2.4 Environmental issues

2.4.1 Methods to reduce transmission of Aspergillus during building work. There are a number of studies that demonstrate an association between building works, environmental contamination with Aspergillus and pulmonary aspergillosis.^127–129 There is good evidence that methods to reduce dust levels result in lower levels of fungal spores in the environment and reduce the incidence of pulmonary aspergillosis during building work. However, there are no studies that systematically look at the risk in relation to the type of building work (construction versus demolition) and relative contributions of various strategies to reduce risk, i.e. (i) dust reduction, (ii) air handling, (iii) environmental and air monitoring, and (iv) antifungal prophylaxis.

There is a financial impact if measures other than simple dust reduction are used and introducing widespread environmental control is expensive, e.g. HEPA filtration. Moreover, there is an absence of evidence that routinely monitoring spore counts during building work is useful, although it is recommended by some authors, especially for high-risk areas.^130–132 Studies have shown that although a protective environment with HEPA filtration reduces the incidence of invasive aspergillosis (IA) in haemopoietic stem cell transplant (HSCT) patients, this may not by itself prevent IA during building work.^131,132

We recommend that during building works, consideration is given to addressing the risk of pulmonary aspergillosis. This must include:

• Identifying high-risk patients, i.e. those with acute leukaemia, HSCT patients, patients receiving chemotherapy resulting in severe, prolonged neutropenia and other immunosuppressed patients including those on long-term corticosteroids or other immunosuppressive therapy.
  
• Methods to reduce all patient's exposure to Aspergillus, e.g. use of floor to ceiling barriers, sealing of windows.
  
• The use of HEPA filtration in high-risk units, e.g. HSCT units and critical care.
  
• Dust reduction in clinical areas including cleaning (damp dusting, use of HEPA-filtered vacuum cleaners).
  

Recommendation Grade B

The routine monitoring of air for fungal spores during building work outside high-risk areas is not recommended. Recommendation Grade D

During building work, environmental monitoring for fungal spores in critical areas housing at-risk patients is useful in monitoring the effectiveness of control measures. Recommendation Grade GPP

In an outbreak situation, environmental or air monitoring may be useful in identifying the source of infection. Recommendation Grade GPP

Ventilation systems, especially those which are not HEPA filtered, may become contaminated during building work. During building work, all filters should be regularly inspected and replaced as necessary. Recommendation Grade GPP

2.4.2 Use of prophylactic antifungal agents during building work. As there have been several outbreaks of Aspergillus infection associated with building work, this raises issues regarding additional patient-focused methods that can be used to prevent infection, including the use of antifungal agents. There is no good evidence for the widespread use of antifungal treatment as prophylaxis during construction work. A small cohort study¹³³ reported that antifungal prophylaxis in immunocompromised patients during construction work reduced IA. There is good evidence for the protective effect against IA of antifungal prophylaxis for neutropenic patients in general^134,135 and specifically to support the use of itraconazole in this situation.^134,136,137 There is no clear evidence-based indication against the use of any antifungal prophylaxis.¹³⁸

We recommend that where there is a high institutional rate of IA or building work is underway, a risk assessment should be undertaken. Those patients who are immunosuppressed, especially those who are neutropenic (neutrophil count <0.5 x 10⁹/L for more than 2 weeks or <0.1 x 10⁹/L for 1 week), who are visiting hospital regularly or staying as an inpatient but not in a HEPA-filtered environment should be considered for antifungal prophylaxis.¹³⁹ Recommendation Grade D

The use of antifungals to prevent IA in the immunosuppressed during building work should be based on a robust risk assessment for the individual patient. Recommendation Grade GPP

The cost of using antifungal prophylaxis should therefore be considered in all building projects (cost of drug and monitoring). In large hospital projects, e.g. involving demolition and reconstruction, the additional cost may need to cover several months. Recommendation Grade GPP

2.4.3 Legionella control. There is a good evidence base showing a relationship between Legionella contamination of hospital water with hospital-acquired (HA) Legionella pneumonia and also good evidence that controlling the risk of Legionella in hospital water supplies reduces the risk of HA Legionella pneumonia. There is a large body of evidence regarding methods to control Legionella in hospital water supplies consisting of cohort and case–control studies.^140–149 The Health and Safety Executive (HSE) has also issued comprehensive guidance on the control of Legionella in hospitals,¹⁵⁰ which has recently been revaluated.¹⁵¹

The methods available to control Legionella in water systems include: (i) heat; (ii) biocides, e.g. chlorine, chlorine dioxide; (iii) ionization, e.g. copper–silver; and (iv) ultraviolet light and ozone.

There are few studies comparing the different methods. Results across the methods are consistent in demonstrating that each process has an effect in reducing Legionella load in hospital waters although the effect may be only temporary. However, it is not possible to make full comparisons between the different methods. Hospitals should already be adhering to DH advice for control of Legionella in hospitals so there should be no additional financial consequences. Research is required to confirm the relationship between environmental Legionella and HA Legionnaire's disease, including establishing the relative importance of different serogroups of Legionella pneumophila and other Legionella spp. Research is required into the different methods of controlling Legionella appropriate for use in different healthcare settings.

Although no recommendation can be made about the most appropriate method, we recommend that in line with the current guidance, appropriate Legionella control of hospital water is required. Recommendation Grade B

UK HSE guidance on Legionnaires' disease—control of Legionella bacteria in water systems^150,151 and all other national guidance should be followed. Recommendation Grade GPP

For secondary prevention (i.e. preventing further cases after a case of hospital-acquired infection), additional measures may be required, e.g. use of biocides, heat flush etc. Recommendation Grade GPP

Routine culturing of hospital water for Legionella, while not recommended, is appropriate in high-risk area, e.g. for haemopoietic stem cell and solid organ transplant wards. Infection control teams should work closely with hospital engineers, management and physicians to ensure awareness of HA Legionnaires' disease.¹⁵² Recommendation Grade GPP

2.4.4 Cleanliness of the environment. Cleanliness of the environment has been highlighted by the DH ‘Saving Lives’ initiative as essential to prevent HCAI.⁵ There are a small number of cohort studies that demonstrate environmental risk related to poor cleaning, e.g. for infection with methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile, but these do not relate directly to HAP or specifically to ICUs. There are a small number of studies that describe the environment acting as a reservoir for other organisms causing infection in patients, though these also do not relate directly to HAP or ICUs. These studies demonstrate that taking action to remove the reservoir is effective in preventing infections. The epic project review revealed little research evidence of an acceptable quality upon which to base guidance relating to hospital environmental hygiene.³⁹ However, it noted that there is a large body of clinical evidence, derived from case reports and outbreak investigations, which show links between poor environmental hygiene and the transmission of microorganisms causing HCAI.^153,154

Given that the routes of transmission for organisms causing HAP are different from those described in the available reports, where the issues relate mainly to direct contact and contamination spread, the applicability of the available evidence, which does not directly relate to HAP, is not strong. It is not possible to generalize from the available evidence as this is of a low volume and not directly related to HAP, ICUs or in all instances, cleaning. The small volume of research that is available is consistent in demonstrating that the environment can act as a reservoir for infection and that taking action to remove the reservoir is effective in preventing infection. The consistency of the evidence makes extrapolation to these issues reasonable. There are now published cleanliness standards for health-providing facilities and these form part of performance assessment reviews.^155,156

We recommend that in order to reduce the risks of HCAI (including HAP), good approved standards of hospital cleanliness should be maintained. Recommendation Grade D

The hospital environment must be visibly clean, free from dust and soilage and acceptable to patients, their visitors and staff. Recommendation Grade GPP

All staff involved in hospital hygiene activities should undergo education and training related to the prevention of HCAI: such training to include the link between these infections and the cleanliness of the environment. Recommendation Grade GPP

	3. Diagnosis

Top Abstract Contents 1. Introduction 2. Prevention 3. Diagnosis 4. Treatment 5. Conclusions Addendum Funding Transparency declarations Comment on the editorial... References

 
3.1 General issues in the diagnosis of HAP

3.1.1 Definitions of HAP. HAP (or NP) is usually defined as pneumonia developing 48 h after admission to hospital that was not incubating at the time of admission.^7,157,158 VAP is usually defined as pneumonia developing 48 h after implementing ET intubation and/or mechanical ventilation that was not present before intubation.^{3,7,157–160}

HAP can be divided into early- and late-onset. Early-onset disease occurs within 4–5 days of admission and tends to be caused by antibiotic-susceptible community-type pathogens, whereas late infections tend to be caused by antibiotic-resistant hospital opportunists. However, some studies have found an increasing frequency of early-onset HAP caused by pathogens more commonly associated with nosocomial disease. This has contributed to the concept of healthcare-associated pneumonia (HCAP), involving pathogens associated with recent prior hospitalization and/or antimicrobial therapy. HCAP has been defined as pneumonia occurring in any patient who had been admitted to an acute care hospital for 2 or more days within 90 days of the infection; or had been a resident in a nursing home or long-term care facility; or had attended a hospital or haemodialysis clinic; or had received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection.⁷ Rarely, HAP/VAP is due to fungal infection and this is usually, although not exclusively, seen in severely immunocompromised patients.

VAP also can be divided into early- and late-onset. Early-onset VAP occurs during the first 4 days of mechanical ventilation when the pneumonia is often caused by typical community organisms. Late-onset VAP develops 5 days after the initiation of mechanical ventilation and is commonly caused by typical opportunistic and antibiotic-resistant hospital pathogens such as P. aeruginosa or MRSA.^3,158,159

3.1.2 Issues in assessing the literature on diagnosis of HAP. There are two fundamental problems with assessing the diagnostic literature relating to HAP. The first is that most publications deal with VAP, whereas most HAP occurs in non-ventilated and non-intubated patients. It may not be valid to extrapolate diagnostic criteria for VAP to HAP; for example, the diagnosis of VAP often involves invasive microbiological sampling, which may not be possible or appropriate in non-intubated patients. The second problem is that there are no universally accepted ‘gold’ or reference standard diagnostic criteria for HAP or VAP. Because of this, it is difficult to compare different diagnostic methods. Most studies begin by dividing patient groups into those with pneumonia and those without, but the criteria used for this division vary, and all have their problems. Thus, most studies have groups of patients that probably have pneumonia or probably do not, and in each there is an unknown proportion that will have been wrongly classified. For example, some patients, not thought to have HAP clinically, have been diagnosed at autopsy,¹⁶¹ and vice versa. We have not excluded such studies from this analysis, but have interpreted the results with caution. Recently, more useful studies have appeared that avoid these problems by analysing the outcomes of management based on different diagnostic techniques in a single group of patients suspected of having HAP.

3.1.3 An assessment of lung histology and culture as a reference standard for the diagnosis of HAP. As lung biopsies are impractical and associated with risk, they are rarely used for the diagnosis of HAP and are not recommended for this purpose. Nevertheless, histology and cultures of homogenized lung tissue have frequently been used to validate other diagnostic tests such as the quantitative microbiology of respiratory specimens.

An experimental baboon model of VAP has been used to assess the severity of bronchopneumonia by lung histology and to compare this with quantitative microbiology of lung tissue and bronchoalveolar lavage (BAL) specimens.¹⁶² Moderate/severe pneumonia as judged by histology was associated with high bacterial concentrations in homogenized lung biopsies, and bacterial concentrations in BALs were linearly related to tissue values. This led to the concept that quantitative bacteriology of a BAL or other deep respiratory specimen could be used for the accurate diagnosis of HAP/VAP. Many subsequent studies of pneumonia in human patients have used lung histology (or quantitative microbiology of respiratory secretions) as the reference standard for assessment of other diagnostic methods.

However, several studies of lung biopsy and culture have shown inconsistent results. In a prospective case study, post mortem lung biopsies were performed <1 h after death on 39 patients who had been mechanically ventilated for 14 days.¹⁶³ Histological pneumonia was diagnosed by four independent pathologists in 7, 9, 12 and 15 cases (18% to 38%), respectively. One of the pathologists reviewed the slides blindly 6 months later and re-classified two patients (one diagnosed with and one without pneumonia). A single pathologist then reviewed the slides by the Johanson et al.¹⁶² criteria and diagnosed pneumonia in 14 patients (36%).¹⁶³ A later prospective case study of quantitative microbiology of open lung biopsies of ventilated patients found that histological lesions of pneumonia and tissue concentrations of bacteria were unevenly distributed through the lung parenchyma.¹⁶⁴ Quantitative tissue bacterial concentrations tended to correlate with the presence and severity of histological lesions, but could not differentiate the histological presence or absence of pneumonia. Similar results have been obtained by others.^165–167

We recommend that lung histology should not be relied upon as a gold/reference standard for the diagnosis of HAP. Recommendation Grade D

When biopsy is used as the reference standard for other diagnostic methods in HAP, the histological criteria should be standardized. Recommendation Grade GPP

The histological diagnosis of HAP or quantification of bacterial lung tissue concentrations should be based on several specimens from different areas of the lung. Recommendation Grade GPP

Studies using histology or parenchymal cultures as the reference standard for assessment of other diagnostic criteria in HAP should be interpreted with caution. Recommendation Grade GPP

3.2 The clinical diagnosis of HAP

3.2.1 Clinical diagnostic criteria. The clinical diagnosis of pneumonia, HAP and VAP is difficult and there are no universally accepted clinical criteria. A systematic review covering the clinical diagnosis of VAP considered publications up to 1998,¹⁶¹ whereas other evidence comprises cohort studies^168,169 or consensus opinion.⁸

Clinical diagnostic criteria described in consensus opinion statements^3,8,158,170 are the same for VAP, HAP and community- acquired pneumonia (CAP). However, there is overlap of clinical signs and symptoms between pneumonia and other forms of sepsis, and the diagnosis of HAP often cannot be made on clinical criteria alone.

With these reservations, the diagnostic sensitivity of clinical suspicion can be improved by taking account of the presence of fever (core temperature >38.3°C), blood leucocytosis (>10 000 leucocytes/mm³) or leucopenia (<4000/mm³), purulent tracheal secretions and the presence of a new and/or persistent infiltrate on chest radiograph (CXR), which is otherwise unexplained.¹⁶¹ However, if all these clinical criteria were required for diagnosis, the specificity would be poor.¹⁶¹ A European consensus group¹⁷⁰ believed that a diagnosis of pneumonia could be based on pulmonary infiltrates plus two of the other criteria.

In some patients, increasing severity of pneumonia may be associated with increasing evidence of circulatory collapse (shock, tachycardia, hypotension and elevated blood urea concentrations).^171,172 However, these signs of sepsis are not specific for pneumonia and are not required for diagnosis of HAP or VAP. In a comparative study, immediate post mortem histology in 39 patients who had been mechanically ventilated for 14 days was assessed against five clinical diagnostic criteria (fever, leucocytosis, positive sputum culture, worsening CXR changes and worsening gas exchange).¹⁷³ None of the individual clinical criteria or any combination of them correlated with the presence or absence of histological pneumonia. Thus, there is only a moderate amount of evidence comparing clinical diagnostic criteria with reference criteria, including histology, and these data demonstrate that there can be considerable variation in the clinical presentation of HAP and that distinction from other forms of sepsis is difficult.

3.2.2 The