Journal of Hospital Infection 92 (2016) 273e279

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Journal of Hospital Infection

journal homepage: www.elsevierhealth.com/journals/jhin

Diagnosis and features of hospital-acquired pneumonia:

a retrospective cohort study
C.D. Russell a, O. Koch a, I.F. Laurenson b, D.T. O’Shea a, R. Sutherland a,
C.L. Mackintosh a, *
a
Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK
b
Clinical Microbiology, Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK

A R T I C L E I N F O S U M M A R Y

Article history: Background: Hospital-acquired pneumonia (HAP) is defined as radiologically confirmed

Received 5 October 2015 pneumonia occurring
48 h after hospitalization, in non-intubated patients. Empirical
Accepted 19 November 2015 treatment regimens use broad-spectrum antimicrobials.
Available online 15 December Aim: To evaluate the accuracy of the diagnosis of HAP and to describe the demographic
2015 and microbiological features of patients with HAP.
Methods: Medical and surgical inpatients receiving intravenous antimicrobials for a clin-
Keywords: ical diagnosis of HAP at a UK tertiary care hospital between April 2013 and 2014 were
Diagnosis identified. Demographic and clinical details were recorded.
Hospital-acquired pneumonia Findings: A total of 166 adult patients with a clinical diagnosis of HAP were identified. Broad-
Nosocomial infection spectrum antimicrobials were prescribed, primarily piperacillinetazobactam (57.2%) and
co-amoxiclav (12.5%). Sputum from 24.7% of patients was obtained for culture. Sixty-five
percent of patients had radiological evidence of new/progressive infiltrate at the time of
HAP treatment, therefore meeting HAP diagnostic criteria (2005 American Thoracic Society/
Infectious Diseases Society of America guidelines). Radiologically confirmed HAP was asso-
ciated with higher levels of inflammatory markers and sputum culture positivity. Previous
surgery and/or endotracheal intubation were associated with radiologically confirmed HAP.
A bacterial pathogen was identified from 17/35 sputum samples from radiologically
confirmed HAP patients. These were Gram-negative bacilli (N ¼ 11) or Staphylococcus aureus
(N ¼ 6). Gram-negative bacteria tended to be resistant to co-amoxiclav, but susceptible to
ciprofloxacin, piperacillinetazobactam and meropenem. Five of the six S. aureus isolates
were meticillin susceptible and all were susceptible to doxycycline.
Conclusion: In ward-level hospital practice ‘HAP’ is an over-used diagnosis that may be
inaccurate in 35% of cases when objective radiological criteria are applied. Radiologically
confirmed HAP represents a distinct clinical and microbiological phenotype. Potential risk
factors were identified that could represent targets for preventive interventions.
ª 2015 The Authors. Published by Elsevier Ltd
on behalf of the Healthcare Infection Society. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

* Corresponding author. Address: Regional Infectious Diseases Unit,

Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.
Introduction
Tel.: þ44 131 537 2848.
E-mail address: Claire.L.Mackintosh@nhslothian.scot.nhs.uk The syndrome of hospital-acquired pneumonia (HAP) is
(C.L. Mackintosh). defined as pneumonia occurring in non-intubated patients

http://dx.doi.org/10.1016/j.jhin.2015.11.013
0195-6701/ª 2015 The Authors. Published by Elsevier Ltd on behalf of the Healthcare Infection Society. This is an open access article
under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
274 C.D. Russell et al. / Journal of Hospital Infection 92 (2016) 273e279

Table I
Patient characteristics
Characteristics All patients Radiologically confirmed HAP Radiology inconsistent with HAP P-valuea
(N ¼ 166) (N ¼ 108) (N ¼ 54)
Male 99 (59.6%) 67 (62.0%) 31 (57.4%) 0.6
Age
Median years (IQR) 79.5 (69e87) 77 (68e86) 81 (71e88)

65 years 138 (83.1%) 88 (81.5%) 46 (85.2%) 0.7

75 years 104 (62.7%) 63 (58.3%) 38 (70.4%) 0.2
Admitted by medicine 125 (75.3%) 75 (69.4%) 46 (85.2%) 0.04
Admitted by surgery 41 (24.7%) 33 (30.6%) 8 (14.8%)
Emergency surgery 24 19 5 1.0
Elective surgery 17 14 3
Nursing home resident 5 (3.0%) 2 (1.9%) 3 (5.6%) 0.3
Medical history
COPD 45 (27.1%) 32 (29.6%) 12 (22.2%) 0.4
Asthma 11 (6.6%) 10 (9.3%) 1 (1.9%) 0.1
Bronchiectasis 4 (2.4%) 3 (2.8%) 1 (1.9%) 1.0
Pulmonary fibrosis 2 (1.2%) 2 (1.9%) 0 0.6
Other lung disease 4 (2.4%) 3 (2.8%) 1 (1.9%) 1.0
IHD 36 (21.7%) 22 (20.4%) 13 (24.1%) 0.7
Heart failure 34 (20.5%) 22 (20.4%) 11 (20.4%) 1.0
Stroke/TIA 43 (25.9%) 26 (24.1%) 17 (31.5%) 0.3
Other neurological disease 10 (6.0%) 7 (6.5%) 2 (3.7%) 0.7
Cognitive impairment 32 (19.3%) 17 (15.7%) 13 (24.1%) 0.2
Chronic liver disease 3 (1.8%) 3 (2.8%) 0 0.6
Chronic kidney disease 15 (9.0%) 6 (5.6%) 9 (16.7%) 0.04
Solid malignancy 23 (13.9%) 11 (10.2%) 11 (20.4%) 0.09
Haematological malignancy 5 (3.0%) 3 (2.8%) 2 (3.7%) 1.0
Type 1 DM 3 (1.8%) 1 (0.9%) 3 (5.6%) 0.1
Type 2 DM 29 (17.5%) 19 (17.6%) 9 (16.7%) 1.0
Immunosuppressive drugs 1 (0.6%) 1 (0.9%) 0 1.0
Dysphagia/GI dysmotility/NG 33 (19.9%) 25 (23.1%) 8 (14.8%) 0.3
tube fed (new or old)
HAP, hospital-acquired pneumonia; IQR, interquartile range; COPD, chronic obstructive pulmonary disease; IHD, ischaemic heart disease; TIA,
transient ischaemic attack; DM, diabetes mellitus; GI, gastrointestinal; NG, nasogastric.
a
Comparing patients with radiologically confirmed HAP and patients with radiology inconsistent with HAP; chi-square test or Fisher’s exact test
depending on number of subjects.

48 h after hospitalization, and therefore not incubating at the the pathogenesis and microbiology of VAP, facilitated by the
time of admission.1 This is distinct from ventilator-associated ease of obtaining deep respiratory samples by bronchoalveolar
pneumonia (VAP), which is defined as pneumonia occurring lavage in intubated patients. Importantly, there are evidence-
after 48e72 h of mechanical ventilation in an intubated pa- based ‘care bundles’ to prevent VAP, but not HAP.7
tient. HAP may be suspected if a patient develops new symp- Empirical treatment of HAP aims to include cover for noso-
toms and signs consistent with respiratory tract infection comial pathogens, especially Gram negative bacteria, there-
(fever, abnormal chest examination, purulent sputum, fore it necessitates using broad-spectrum agents such as co-
tachypnoea, impaired oxygenation) and laboratory results amoxiclav and piperacillinetazobactam, with the attendant
consistent with inflammation (raised white cell count and C- risks of antibiotic-associated diarrhoea, C. difficile infection,
reactive protein). However, the diagnosis of HAP also requires selection for antimicrobial resistance in patient and environ-
radiological demonstration of a new or progressive lung infil- mental flora and also high costs. An accurate diagnosis of HAP is
trate.1 American Thoracic Society/Infectious Diseases Society therefore essential to ensure appropriate use of these
of America (ATS/IDSA) guidelines for the management of HAP antimicrobials.
highlight Gram-negative bacilli as frequently occurring patho- The aim of this study was to retrospectively evaluate the
gens in HAP and Staphylococcus aureus as an emerging cause. accuracy of the diagnosis of HAP in inpatients on acute internal
Much of the literature that has been used to describe the medicine and general surgical wards receiving intravenous
aetiology of HAP relates to VAP, nosocomial pneumonia antimicrobials for a clinical diagnosis of HAP made by the pa-
occurring specifically in the intensive care unit (ICU) or nursing- tient’s team. The demographic and microbiological features of
home-acquired pneumonia.1e6 Overall, more is known about patients with radiologically confirmed HAP will be described.
 C.D. Russell et al. / Journal of Hospital Infection 92 (2016) 273e279 275

Table II
Admission events, chest X-ray features, antimicrobial treatment, and outcomes
All patients Radiologically confirmed HAP Radiology inconsistent with HAP P-valuea
(N ¼ 166) (N ¼ 108) (N ¼ 54)
Admission events
Surgery pre HAP 39 (23.5%) 33 (30.6%) 6 (11.1%) 0.006
ICU admission pre HAP 29 (17.5%) 23 (21.3%) 6 (11.1%) 0.13
Intubation pre HAPb 45 (27.1%) 36 (33.3%) 8 (14.8%) 0.01
Admission CXR features
Clear lung fields 103 (62.0%) 65 (60.2%) 37 (68.5%) 0.4
Consolidation 15 (9.0%) 8 (7.4%) 7 (13.0%) 0.3
Features of heart failure 10 (6.0%) 6 (5.6%) 4 (7.4%) 0.7
No admission CXR 10 (6.0%) 7 (6.5%) 2 (3.7%) 0.7
Antimicrobial treatment
Piperacillinetazobactam 151 (57.2%) 107 (60.8%) 44 (50%) 0.1
Co-amoxiclav 33 (12.5%) 18 (10.2%) 15 (17.0%) 0.1
Metronidazole 22 (8.3%) 10 (5.7%) 12 (13.6%) 0.03
Vancomycin 19 (7.2%) 11 (6.3%) 8 (9.1%) 0.5
Ciprofloxacin 13 (4.9%) 7 (4.0%) 6 (6.8%) 0.4
Meropenem 13 (4.9%) 12 (6.8%) 1 (1.1%) 0.07
Ceftriaxone 4 (1.5%) 3 (1.7%) 1 (1.1%) 1.0
Amoxicillin 3 (1.1%) 3 (1.7%) 0 0.6
Gentamicin 2 (0.8%) 1 (0.6%) 1 (1.1%) 1.0
Clarithromycin 1 (0.4%) 1 (0.6%) 0 1.0
Linezolid 1 (0.4%) 1 (0.6%) 0 1.0
Minimum antimicrobial 4 (3e5) 4 (3e6) 3.5 (2e5) 0.04
duration, median days (IQR)
Outcomes
ICU admission 6 (3.6%) 6 (5.6%) 0 0.2
Intubation and ventilation 6 (3.6%) 6 (5.6%) 0 0.2
Death during admission 32 (19.3%) 22 (20.4%) 10 (18.5%) 0.8
HAP, hospital-acquired pneumonia; ICU, intensive care unit; CXR, chest X-ray; IQR, interquartile range.
a
Comparing patients with radiologically confirmed HAP and patients with radiology inconsistent with HAP; chi-squared test or Fisher’s exact test
depending on number of subjects or two-sample Wilcoxon rank sum (WhitneyeMann) when comparing two medians.
b
For emergency airway management, mechanical ventilation or general anaesthesia for surgery.

Methods Definitions

Patients The presence of signs and/or symptoms consistent with

respiratory tract infection was assumed based on the clin-
This was a retrospective observational cohort study of ical diagnosis of HAP made by the patient’s clinicians
48 h
medical and surgical inpatients receiving intravenous antimi- after admission to hospital. To be classified as radiologi-
crobials for a clinical diagnosis of HAP at a tertiary care hospital cally confirmed HAP in this study, chest X-ray evidence of a
in Edinburgh, UK. Data were collected as part of a large pro- new or progressive lung infiltrate was required (reported
spective audit of antimicrobial prescribing in all inpatients by a radiologist), consistent with the 2005 ATS/IDSA
within acute internal medicine and general surgery wards of guidelines.1
the Royal Infirmary of Edinburgh (RIE) over 13 months, between
April 2013 and April 2014. All patients treated with intravenous
antimicrobials for
48 h for any indication were identified and
reviewed by a consultant infectious disease physician and an Analysis
antimicrobial pharmacist. To be included in the current study,
a patient from this cohort had to be receiving intravenous Fisher’s exact test was used to compare categorical vari-
antimicrobials for a documented clinical diagnosis of HAP, ables if one cell contained five or fewer subjects; chi-square
excluding VAP and CAP. Demographic data, medical history, test was used if all cells contained more than five subjects.
admission details (including death during admission), clinical The ShapiroeWilk W-test for non-normality was used to assess
diagnosis (as deduced by the primary clinical team), micro- the distribution of continuous data and the ManneWhitney
biological sampling, and radiological investigations were U-test was used for data not in a normal distribution. Data were
collected. Antimicrobial susceptibility testing was carried out analysed using StatsDirect software version 2.8.0 (StatsDirect,
using the European Committee on Antimicrobial Susceptibility Altrincham, UK). P < 0.05 was considered statistically
Testing (EUCAST) methodology. significant.
276 C.D. Russell et al. / Journal of Hospital Infection 92 (2016) 273e279

Table III patients was sent for culture. Six percent of patients had a
Comparison of inflammatory markers throat swab tested by quantitative polymerase chain reaction
(qPCR) for influenza A, influenza B, respiratory syncytial virus,
Inflammatory Radiologically Radiology P-
parainfluenza virus types 1e3, adenovirus, human corona-
marker confirmed HAP inconsistent valuea
viruses 229E, HKU1, NL63 and OC43, human metapneumovirus
with HAP
rhinovirus, and Mycoplasma pneumoniae. Meticillin-resistant
(N ¼ 108) (N ¼ 54)
Staphylococcus aureus (MRSA) screening was performed in
White cell count 14.7 11.0 0.0002 80.7% of patients during their admission. Following initiation of
(mean, 109/L) treatment for suspected HAP, 4.2% of patients had a positive
Neutrophil count 12.5 8.8 0.0001 C. difficile toxin assay result and an additional 4.2% had an
(mean, 109/L) equivocal result (C. difficile screening test positive but
C-reactive protein 150.6 88.1 0.0003 C. difficile toxin not detected) during their hospital admission
(mean, mg/L) following treatment for HAP.
HAP, hospital-acquired pneumonia.
a
The ShapiroeWilk test demonstrated that the data were not nor-
mally distributed, so the ManneWhitney U-test was used to compare
Radiologically confirmed diagnosis of HAP
these continuous variables.
Of all 166 patients treated for a clinical diagnosis of HAP,
65.1% had radiological evidence of a new or progressive lung
Results infiltrate at the time of commencement of HAP treatment.
Assuming the presence of consistent clinical signs and/or
Characteristics of patients treated for a clinical symptoms in addition, based on the clinical diagnosis of HAP,
diagnosis of HAP these patients are considered to have met diagnostic criteria
for HAP according to the 2005 ATS/IDSA guidelines.1 In 32.5%,
Over the 13-month time-period, a total of 13,096 admissions chest imaging found no evidence of a new or progressive infil-
to eight wards in the RIE were reviewed. Overall 1745 of these trate. No chest imaging was performed for four patients, and
adult inpatients received
48 h of intravenous antimicrobials these patients were excluded from the following analyses.
(13.3%). Of these, 166 were treated for a clinical diagnosis of Radiologically confirmed HAP appeared to represent a
HAP (9.51% of patients on intravenous antimicrobials) (Table I). distinct clinical phenotype, with significantly higher levels of
The cohort of patients was elderly, with a median age of 79.5 inflammatory markers (white cell count, neutrophils, and C-
years. The majority of patients were aged
75 years (62.7%) and reactive protein; P < 0.05 for all) in these patients (Table III).
were male (59.6%); 75.3% of patients had been admitted to a Patients with radiologically confirmed HAP were more likely to
medical ward, and 24.7% to a surgical ward. Comorbidities, for have a white cell count greater than the upper limit of the local
example chronic obstructive pulmonary disease, heart failure and reference range [odds ratio (OR): 3.23; 95% confidence interval
cardio-/cerebrovascular disease, were widespread in the cohort, (CI): 1.57e6.83; P ¼ 0.0007]. Leucopenia was only observed in
reflected in an inpatient mortality of 19.3% (Table II). Median one patient from each group. When the total duration of
number of comorbidities was 2 with 28.3% of patients having >2. intravenous antimicrobial therapy was considered, patients
Of the patients treated for HAP, 23.5% underwent a surgical with radiologically confirmed HAP had a longer median mini-
procedure under general anaesthetic prior to diagnosis and mum duration of treatment (3.5 days vs 4 days; P ¼ 0.04;
treatment (Table II). A slightly higher percentage (27.1%) had Table II) further suggesting that the two groups were clinically
previously undergone endotracheal intubation during the different.
admission, reflecting some patients requiring intubation for There was no significant difference in the use of piper-
airway management or mechanical ventilation in the ICU, over acillinetazobactam, co-amoxiclav, vancomycin, ciprofloxacin
and above those intubated for general anaesthesia. Six patients or meropenem between patients with and without radiological
treated for a clinical diagnosis of HAP required ICU admission confirmation of HAP. The mortality rate during admission for
and mechanical ventilation following clinical diagnosis of HAP. patients with radiologically confirmed HAP was 20.4%, with
The majority of patients had clear lung fields reported by a 5.6% of patients requiring admission to the ICU and mechanical
radiologist on their admission chest X-ray. Nine percent of ventilation following HAP diagnosis. In the group without
patients had consolidation reported on admission, representing radiological confirmation, no patients went on to require ICU
an initial presentation with community-acquired pneumonia or admission and the mortality rate during admission was 18.5%
aspiration pneumonia before suspicion of and treatment for (P ¼ 0.8).
HAP arising
48 h after admission.
In accordance with local guidelines for the treatment of
HAP, piperacillinetazobactam was the most frequently used Demographics associated with radiologically
antimicrobial, prescribed to 57.2% of included patients confirmed HAP
(Table II). Co-amoxiclav was the second most widely prescribed
antimicrobial, used in 12.5% of cases. Patient characteristics and admission details were
compared between patients treated for HAP with and without
Microbiological sampling in patients treated for a radiological confirmation of a new/progressive infiltrate
clinical diagnosis of HAP (Tables I and II). Being admitted to a surgical ward (OR: 2.52,
95% CI: 1.03e6.87; P ¼ 0.04), undergoing surgery (requiring
In our study, blood cultures were drawn in the majority of general anaesthesia and intubation) (3.49; 1.31e10.98;
patients treated for HAP (75.9%). Sputum from 24.7% of P ¼ 0.006) or endotracheal intubation for any indication (2.85;
 C.D. Russell et al. / Journal of Hospital Infection 92 (2016) 273e279 277

Table IV one each. The patient with S. pneumoniae bacteraemia asso-

Microbiology results in patients with radiologically confirmed ciated with HAP had clear lung fields on admission chest X-ray.
HAP A throat swab for qPCR testing for respiratory pathogens was
obtained from 5.6% of patients and was negative in all cases.
Sample No.
MRSA was found in only five of 90 MRSA screens (taken any time
Sputum culture (N ¼ 35) during admission) and was identified from one sputum sample
No growth 5 and one blood culture (from different patients). Both of these
Commensals 5 patients had a positive MRSA screen.
Yeasts 6 An antibiogram of the antimicrobial susceptibilities of bac-
Coliforms 4 teria isolated from sputum samples is shown in Supplementary
Escherichia coli 5 Table I. Overall, Gram-negative bacteria tended to be resistant
Pseudomonas aeruginosa 4 to amoxicillin and co-amoxiclav, but susceptible to ciproflox-
Staphylococcus aureus (MSSA) 5 acin, gentamicin, piperacillinetazobactam, and meropenem.
Staphylococcus aureus (MRSA) 1 Five out of six S. aureus isolates were susceptible to fluclox-
Enterobacter cloacae 1 acillin and all six were susceptible to doxycycline (including the
Klebsiella oxytoca 1 one MRSA isolate). The MRSA sputum isolate was susceptible to
Aspergillus fumigatusa 1 vancomycin.
Blood culture (N ¼ 85)b
No growth 81
Klebsiella pneumoniae 1 Discussion
Staphylococcus aureus (MRSA) 1
Proteus mirabilis 1 We have retrospectively evaluated a cohort of 166 medical
Streptococcus pneumoniae 1 and surgical inpatients treated for a clinical diagnosis of HAP.
MRSA screen (N ¼ 90) Applying the 2005 ATS/IDSA HAP guidelines to these patients,
Positive 5 we identified that only 65.1% of patients had radiologically
qPCR for respiratory pathogensc (N ¼ 6) confirmed HAP; therefore it appears that in ward-level hospital
Any positive result 0 practice at our institution ‘HAP’ is an over-used diagnosis that
HAP, hospital-acquired pneumonia; MRSA, meticillin-resistant may be inaccurate in more than one-third of cases. Surgical
S. aureus; MSSA, meticillin-susceptible S. aureus. ward admission, undergoing surgery with general anaesthesia,
a
Single isolate, likely contaminant. or endotracheal intubation for any indication were associated
b
All patients with positive blood cultures at time of HAP diag- with radiologically confirmed HAP.
nosis had negative blood cultures earlier in admission. The 2005 ATS/IDSA guidelines describe intubation and me-
c
Influenza A, influenza B, respiratory syncytial virus, para-
chanical ventilation as a risk factor for developing nosocomial
influenza virus types 1e3, adenovirus, human coronaviruses 229E,
pneumonia, but the literature cited to support this statement
HKU1, NL63 and OC43, human metapneumovirus, rhinovirus, and
Mycoplasma pneumoniae. describes VAP, i.e. the development of pneumonia in patients
during mechanical ventilation.1 Hypothesis-generating univar-
iate analysis on our data suggests that intubation and ventila-
1.17e7.76; P ¼ 0.01) were all associated with radiologically tion, especially when associated with surgery, may be a
confirmed HAP. In surgical patients, there was no difference continuing risk factor for pneumonia even following extubation
between emergency/elective admissions. Patients from both and is therefore a relevant factor when assessing non-
groups had a median of two medical comorbidities, and aside intubated patients with new respiratory signs and symptoms
from CKD no comorbidity was associated with radiologically in hospital. The pathogenesis of HAP may therefore often be
confirmed HAP. related to microaspiration of oropharyngeal contents around
the cuff of an endotracheal (ET) tube in paralysed intubated
Microbiology of radiologically confirmed HAP patients during surgery, without necessarily a prolonged period
of mechanical ventilation such as during critical illness (i.e.
Rates of microbiological sampling in patients with radio- VAP). In a systematic literature review of airway management
logically confirmed HAP were similar to the overall population strategies to reduce the incidence of VAP in critically ill
of patients treated for clinical suspicion of HAP. A bacterial ventilated patients in the ICU, interventions including contin-
pathogen was identified from 17 of 35 sputum samples from uous aspiration of subglottic secretions using a special ET tube
patients with radiologically confirmed HAP (48.6%; Table IV). (vs standard ET tubes) and the use of heat and moisture ex-
The majority of bacterial species identified in sputum samples changers have been shown to lower VAP rates.8 In a separate
were Gram-negative bacilli (N ¼ 11) and S. aureus (N ¼ 6). study, persistent ET tube cuff pressure of <20 cmH2O was also
Sputum samples were obtained from six patients without associated with risk of VAP.9 Such interventions could also be
radiologically confirmed HAP and none of these yielded growth evaluated in intubated patients undergoing surgery. Similarly,
of a bacterial pathogen. in critically ill ventilated patients, oral hygiene with chlor-
Blood cultures were drawn in 78.7% of patients with radio- hexidine mouthwash has been shown to reduce rates of VAP,
logically confirmed HAP and bacteraemia was infrequent, and has been included as a component of a successfully eval-
occurring in only four patients (sputum cultures were not ob- uated ‘VAP care bundle’.7,10 Chlorhexidine mouthwash would
tained from any of the patients with bacteraemia). Gram- be an inexpensive measure for use in the immediate pre- and
negative bacteria were responsible for two of these blood- postoperative period for surgical patients. Oral care (chlor-
stream infections, and MRSA and S. pneumoniae accounted for hexidine mouthwash or mechanical cleaning) was shown to be
278 C.D. Russell et al. / Journal of Hospital Infection 92 (2016) 273e279
associated with a reduced relative risk of pneumonia in a meta- database of patients with culture-positive pneumonia,
analysis incorporating non-ventilated hospital inpatients and including 835 patients with HAP.14 Here, S. aureus accounted
nursing home residents (though there was a high risk of bias in for 47.1% of cases, Pseudomonas spp. 18.4%, Klebsiella spp.
included studies).11 Other postoperative factors likely to be 7.1%, Haemophilus spp. 5.6%, E. coli 4.7%, Enterobacter spp.
important in development of HAP include being bed-bound, 4.3%, and Acinetobacter spp. 2.0%. Overall, Gram-negative
having reduced chest wall movement (and therefore reduced pathogens were isolated from 45.8% of HAP cases. A compli-
clearance of secretions) due to pain or being drowsy secondary cating factor in conventional culture-based testing of samples
to opiate analgesics. from patients with suspected HAP is the fact they will most
In approximately one-third of patients treated for suspected likely already have received antimicrobials prior to sampling,
HAP in this study, a chest X-ray or computed tomography (CT) impairing sensitivity of pathogen detection using culture-based
excluded a pneumonic infiltrate, therefore an alternative techniques. A qPCR test for detection and quantification of
diagnosis may have been missed. A phenotype has been eight key bacterial causes of pneumonia (including S. aureus,
described in ventilated ICU patients with respiratory signs but E. coli and P. aeruginosa) from sputum samples has recently
no infiltrate on chest imaging, labelled nosocomial tracheo- been described and could represent a useful tool for the
bronchitis.12 This has been associated with longer ICU admis- investigation of suspected HAP.15
sion and ventilation times but prospective data describing the Only six (5.6%) patients with HAP had throat swabs obtained
necessity for antimicrobials are lacking.12 Further study of this for qPCR respiratory virus and M. pneumoniae testing and in all
phenotype in non-intubated patients may be valuable and it cases these were negative. Nosocomial influenza can account
may account for some of the cases in this study without for a significant proportion of influenza cases (17.3% in a Ca-
radiological changes consistent with HAP. Non-infective alter- nadian surveillance programme).16 Using admission to critical
natives include atelectasis, pulmonary embolism, and under- care wards as a marker, the 2013/14 influenza season in Scot-
lying lung disease, such as chronic obstructive pulmonary land was similar to the preceding year with no significant in-
disease (present in 27.1% of patients treated for HAP in this crease in cases.17 However, the lack of consistent testing for
study) and asthma. Unwell patients labelled as ‘HAP’ may have influenza virus in patients with HAP precludes any conclusions
a subdiaphragmatic cause of sepsis resulting in the clinical about the incidence of nosocomial influenza causing HAP dur-
findings. Given the demonstrated difficulty in reaching a reli- ing the study period, or the utility of respiratory virus/myco-
able clinical diagnosis of HAP, microbiological testing to plasma testing in the work-up of suspected HAP.
confirm an infective aetiology becomes even more important, A limitation of this study is that radiological confirmation of
but a sputum sample was obtained from only 24.7% of patients HAP is primarily derived from the results of chest X-rays (only
treated for HAP. This low rate may reflect the difficulty in 10 of the 166 patients underwent CT) which may lead to under-
obtaining a suitable deep specimen from non-intubated pa- detection of pulmonary infiltrates compared to CT.18e20 In a
tients with a degree of respiratory distress or weakness. In such study of 3423 patients presenting to the emergency depart-
patients biomarkers of pulmonary infection would be helpful in ment with respiratory symptoms who underwent both chest X-
establishing the likelihood of an infective aetiology and justi- ray and CT, it has been demonstrated that X-ray has poor
fying the use of empirical antimicrobials prior to culture sensitivity in detecting pulmonary infiltrates in comparison to
results. CT (sensitivity 43.5%).20 The timing of CT scan was not specified
In comparison to community-acquired pneumonia, where in this study, therefore a confounding factor may be that a
the culture-positive rate of sputum samples at our institution possible delay between X-ray and CT allows development of a
has been reported as 30%, a bacterial pathogen was identified detectable infiltrate. In cases where HAP is suspected clinically
from 17 of 35 (48.6%) samples from patients with radiologically but the chest X-ray does not show a new/progressive lung
confirmed HAP and therefore has greater potential to influence infiltrate, there may be a role for CT scanning. In addition,
management.13 In our study, Gram-negative bacilli (11/17) and there is emerging evidence for the role of lung ultrasound for
S. aureus (6/17) were the identified pathogens, with no the detection of pulmonary infiltrates in CAP, with some data
frequently occurring CAP pathogens isolated. In the remainder suggesting superiority over chest X-ray when compared to CT as
of cases where a sputum sample was obtained, the result was a gold standard.21,22 A further limitation lies in the casee
‘no growth’, ‘respiratory commensals’ or ‘yeasts’. Antimicro- control analysis performed, which should be repeated in the
bial resistance was significant, with most Gram-negative iso- future with a control cohort of hospital inpatients with no
lates displaying resistance to amoxicillin and co-amoxiclav, but clinical suspicion of HAP. Furthermore, this study only identi-
susceptibility to piperacillinetazobactam. However, the over- fied patients receiving intravenous antimicrobials, thereby
all number of sputum cultures obtained from patients was low, selecting for patients perceived to have more severe illness.
reducing the utility of these data in describing the microbiology When cases were identified during the antimicrobial pre-
of HAP. In addition, we recognize the potential for contami- scribing audit, a recommendation was made to the parent team
nation of sputum samples with oropharyngeal colonizers. This regarding further antimicrobial management. Whereas this
is an important issue, especially considering the prescription of occurred after the clinical diagnosis of HAP had been made by
broad-spectrum antimicrobials to cover the susceptibility the patient’s team and would have had no influence on this, it
pattern of these pathogens, but pragmatically one would aim may have altered subsequent management. This could there-
to cover these species if they were identified in a sputum fore confound the mortality data presented here, although no
sample from a patient with HAP. As discussed above, the significant difference was observed between patients with and
inability to routinely obtain deep respiratory tract specimens without radiologically confirmed HAP.
(e.g. BAL) from non-intubated patients hinders microbiological This study has described the features of radiologically
diagnosis in HAP. The largest report on the microbiology of HAP confirmed HAP in a cohort of UK inpatients. Potential risk
comes from a retrospective cohort study of a US inpatient factors have been identified through a hypothesis-generating
 C.D. Russell et al. / Journal of Hospital Infection 92 (2016) 273e279 279
caseecontrol analysis using patients treated for suspicion of 7. Morris AC, Hay AW, Swann DG, et al. Reducing ventilator-
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HAP are highlighted in Supplementary Table II. Improved ac- patients to prevent ventilator-associated pneumonia. Cochrane
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alternative diagnosis requiring different investigation and chanical ventilation: a systematic review and meta-analysis of
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Acknowledgements bronchitis in mechanically ventilated patients: incidence, aeti-
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We gratefully acknowledge the assistance of A. Cockburn, L. 13. Chalmers JD, Taylor JK, Singanayagam A, et al. Epidemiology,
Shaw, C. Philip, and D. Reekie (antimicrobial pharmacists), E. antibiotic therapy, and clinical outcomes in health care associ-
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Epidemiology and outcomes of health-care-associated pneumonia:
Conflict of interest statement
results from a large US database of culture-positive pneumonia.
None declared.
Chest 2005;128:3854e3862.
15. Gadsby NJ, McHugh MP, Russell CD, et al. Development of two
Funding sources real-time multiplex PCR assays for the detection and quantifica-
None. tion of eight key bacterial pathogens in lower respiratory tract
infection. Clin Microbiol Infect 2015;21:788.
Appendix A. Supplementary data 16. Taylor G, Mitchell R, McGeer A, et al. Healthcare-associated
influenza in Canadian hospitals from 2006 to 2012. Infect Control
Supplementary data related to this article can be found at Hosp Epidemiol 2014;35:169e175.
http://dx.doi.org/10.1016/j.jhin.2015.11.013. 17. Public Health England. Surveillance of influenza and other
respiratory viruses in the United Kingdom: Winter 2013/14.
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