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ORIGINAL ARTICLE
Nursing-home-acquired pneumonia in Germany: an
8-year prospective multicentre study
Santiago Ewig,
1
Benjamin Klapdor,
1
Mathias W Pletz,
2
Gernot Rohde,
3
Hartwig Schu
¨
tte,
4
Tom Schaberg,
5
Torsten T Bauer,
6
Tobias Welte,
7
for the CAPNETZ
study group
ABSTRACT
Objective To determine differences in aetiologies, initial
antimicrobial treatment choices and outcomes in
patients with nursing-home-acquired pneumonia (NHAP)
compared with patients with community-acquired
pneumonia (CAP), which is a controversial issue.
Methods Data from the prospective multicentre
Competence Network for Community-acquired pneumonia
(CAPNETZ) database were analysed for hospitalised
patients aged $65 years with CAP or NHAP. Potential
differences in baseline characteristics, comorbidities,
physical examination findings, severity at presentation,
initial laboratory investigations, blood gases, microbial
investigations, aetiologies, antimicrobial treatment and
outcomes were determined between the two groups.
Results Patients with NHAP presented with more severe
pneumonia as assessed by CRB-65 (confusion, respiratory
rate, blood pressure, 65 years and older) score than
patients with CAP but received the same frequency of
mechanical ventilation and less antimicrobial combination
treatment. There were no clinically relevant differences in
aetiology, with Streptococcus pneumoniae the most
important pathogen in both groups, and potential
multidrug-resistant pathogens were very rare (<5%). Only
Staphylococcus aureus was more frequent in the NHAP
group (n¼12, 2.3% of the total population, 3.1% of those
with microbial sampling compared with 0.7% and 0.8% in
the CAP group, respectively). Short-term and long-term
mortality in the NHAP group was higher than in the CAP
group for patients aged $65 years (26.6% vs 7.2% and
43.8% vs 14.6%, respectively). However, there was no
association between excess mortality and potential
multidrug-resistant pathogens.
Conclusions Excess mortality in patients with NHAP
cannot be attributed to a different microbial pattern but
appears to result from increased comorbidities, and
consequently, pneumonia is frequently considered and
managed as a terminal event.
INTRODUCTION
The epidemiology of community-acquired pneu-
monia (CAP) has undergone significant changes in
the past few decades. Patients with CAP present at
an increasingly older age and with severe disabil-
ities. Mortality in these patients is usually high,
reaching up to 30%.
1 2
As a consequence, CAP ‘in the elderly’
3e8
and ‘in
the very elderly’
9
has attracted considerable interest
in the investigation of the disease. In particular,
patients living in nursing homes were identified as
those with the highest mortality.
110e12
Data from
the USA indicate an excess of multidrug resistant
(MDR) pathogens in patients with chronic
healthcare contacts, and patients with ‘nursing-
home-acquired pneumonia’ (NHAP) were included
under the concept of ‘healthcare-associated pneu-
monia’ (HCAP).
13 14
The HCAP concept has been subject to criticism.
Whereas there is no doubt that older patients and
those with disabilities have an increased mortality,
the main hypothesis that MDR pathogens account
for this excess mortality remains unproven. More-
over, leading criteria for HCAP, including severe
immunosuppression and recent hospitalisation,
remain questionable. Patients with severe immu-
nosuppression form a distinct group and should not
be included under the concept of HCAP. Recently
hospitalised patients are clearly at risk from MDR
pathogens but should be regarded and managed as
patients with nosocomial pneumonia.
15
If this
Key messages
What is the key question?
<
Nursing-home-acquired pneumonia (NHAP) is
associated with considerably higher mortality
than community-acquired pneumonia (CAP).
<
Whether this higher mortality rate is related to
different aetiologies including potential multidrug
resistant (MDR) pathogens and consequently
inadequate initial antimicrobial coverage
remains a controversial issue.
What is the bottom line?
<
NHAP does not differ from CAP in terms of
aetiology and excess mortality is not related to
the inadequate treatment of potential MDR
pathogens.
<
Excess mortality results from higher comorbid-
ities and pneumonia frequently being considered
and managed as a terminal event of advanced
age and poor functional status.
Why read on?
<
NHAP is a frequent condition.
<
Understanding the reasons for excess mortality
will allow adequate management of these
patients.
1
Thoraxzentrum Ruhrgebiet,
Department of Respiratory and
Infectious Diseases, EVK Herne
and Augusta-Kranken-Anstalt
Bochum, Germany
2
Division of Gastroenterology,
Hepatology and Infectious
Diseases, Jena University
Hospital, Jena, Germany
3
Department of Respiratory
Medicine, Maastricht University
Medical Centre, The
Netherlands
4
Medical Clinic, Infectious
Diseases and Respiratory
Medicine, Charite
´
e Berlin
University, Berlin, Germany
5
Diakoniekrankenhaus,
Respiratory Clinic Unterstedt,
Rotenburg an der Wu
¨
mme,
Germany
6
Lungenklinik Heckeshorn,
Helios Klinikum Emil von
Behring, Berlin, Germany
7
Department of Respiratory
Medicine, Hannover University,
Hannover, Germany
Correspondence to
Prof Santiago Ewig,
Thoraxzentrum Ruhrgebiet,
Kliniken fu
¨
r Pneumologie und
Infektiologie, EVK Herne und
Augusta-Kranken-Anstalt
Bochum, Bergstrasse 26, 44791
Bochum, Germany;
sewig@versanet.de
Received 16 June 2011
Accepted 13 October 2011
Published Online First
5 November 2011
132 Thorax 2012;67:132e138. doi:10.1136/thoraxjnl-2011-200630
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rearrangement is accepted, the only remaining core group of
HCAP is NHAP.
16
We therefore investigated the clinical characteristics, microbial
patterns and outcomes of patients with NHAP included on the
large prospective Competence Network for Community-
acquired pneumonia (CAPNETZ) database. In particular, we
examined the association between aetiology and in-hospital
mortality. Recently, we showed that there are fundamental
differences in aetiology and outcome in younger patients with
CAP compared with those aged $65 years; in fact, it is
a completely separate entity.
17
In view of these data, we thought
it most appropriate to compare hospitalised patients with CAP
or NHAP aged $65 years. This would avoid inflation of differ-
ences due to the younger patient population.
METHODS
Patients
The methodology of CAPNETZ has been reported elsewhere.
18
Overall, 15 local clinical centres throughout Germany were
involved. Prospective patients were those aged $18 years with
a pulmonary infiltrate diagnosed by chest x-ray, clinical symp-
toms of fever, cough, purulent sputum or positive auscultation.
Exclusion criteria were age <18 years, acquired or therapeuti-
cally induced immune deficiency, active tuberculosis or
a possible nosocomial genesis of infection (hospitalisation
<4 weeks prior to infection). Cases were reported to the local
participating clinical centre via a network of sentinel practices
and hospitals.
The study was approved by the central and local ethics
committees
and written informed consent was obtained from all
patients.
Data collection
Demographic, clinical, and diagnostic data were recorded using
standardised web-based data sheets. The study period was
90 months from January 2002 to June 2009.
Microbial investigation
The methods applied have been described previously.
18
Briefly,
samples obtained included sputum and/or other respiratory
secretions, blood cultures, urinary antigen testing for Strepto-
coccus pneumoniae and Legionella pneumophila serogroup 1,
serology, and nasal and pharyngeal swabs. Investigations for
Mycoplasma pneumoniae were performed as described in
a previous report.
19
Investigations for viruses were only car ried
out until July 2007. All samples were immediately processed in
the local participating microbiological laboratories according to
the German Quality Standards in Clinical Microbiology and
Infectious Diseases.
20
To limit possible bias due to incomplete sampling and limited
diagnostic yield of microbial investigation, pathogen frequencies
were reported using the following denominators: total popula-
tion; cases with microbial sampling (including those techniques
able to detect the pathogen in question); cases with a pathogen
determined.
Susceptibility testing was not generally recorded, with the
exception of Staphylococcus aureus. Therefore, all enter-
obacteriaceae, Pseudomonas aeruginosa and S aureus isolates were
considered to be potential MDR pathogens.
CRB-65 score and mortality
The CRB-65 score consists of four variables: confusion, respira-
tory rate $30/min, systolic blood pressure <90 mm Hg or dia-
stolic blood pressure #60 mm Hg, and age $65 years. One
point is given for each parameter present, which results in CRB-
65 scores of 0e4. For each patient the CRB -65 score was
calculated with patient data assessed at first presentation.
Short-term mortality was defined as death within 30 days of
diagnosis and long-term mortality as death within 180 days of
diagnosis.
Statistical analysis
Hospitalised patients aged $65 years with CAP were considered
to represent the current standard group and were compared
with patients aged $65 years with NHAP.
Comparisons between groups were performed by means of
the
c
2
test for categorical variables and the Student t test for
continuous variables (or the non-parametric ManneWhitney U
test when data were not normally distributed). All analyses were
performed using SPSS software (SPSS 19.0; SPSS Inc., Chicago,
IL, USA). All tests of significance were two tailed and a was set
at 0.05.
RESULTS
Patient population
Overall, 3087 hospitalised patients aged $65 years were included
in our analysis. Of these, 518 had NHAP.
Baseline characteristics
The following characteristics were significantly different: the
NHAP group consisted of more women, had lower body mass
index and fewer cases of obesity, were less frequent smokers and
less frequently on long-term oxygen treatment (table 1).
Table 1 Baseline characteristics and comorbidities
Variable
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Age, years (median
(IQR) (n))
76.1 (10.8) (2569) 83.3 (12.0) (518) <0.001
Men, n (%) 1609 (62.6) 221 (42.7) <0.001
Weight, kg (median
(IQR) (n))
74 (20) (2488) 65 (19) (423) <0.001
Height, cm (median
(IQR) (n))
170 (13) (2483) 167 (12) (426) <0.001
BMI, kg/m
2
(median
(IQR) (n))
25.2 (5.7) (2480) 23.0 (5.0) (420) <0.001
Obesity (BMI$30), n (%) 433 (17.5) 31 (7.4) <0.001
Smoker, n (%) 453 (18.3) 40 (8.9) <0.001
Pack-years (median
(IQR) (n))
30 (35) (1095) 30 (28) (78) 0.285
Long-term oxygen
therapy, n (%)
209 (8.2) 16 (3.1) <0.001
Pneumococcal vaccination
in the past 5 years, n (%)
389 (17.1) 27 (9.3) <0.001
Comorbidity, n (%) 2275 (90.2) 376 (97.1) <0.001
Chronic respiratory disease 1197 (46.8) 153 (30.3) <0.001
Congestive heart failure 901 (35.2) 265 (52.1) <0.001
Other heart diseases 1376 (54.0) 258 (51.0) 0.221
Cerebrovascular disease 390 (15.2) 336 (66.1) <0.001
Other chronic neurological
disorder
203 (7.9) 152 (29.9) <0.001
Renal insufficiency 419 (16.4) 121 (24.0) <0.001
Chronic liver disease 83 (3.2) 14 (2.8) 0.575
Diabetes mellitus 726 (28.3) 170 (33.3) 0.022
Malignancy 371 (14.5) 58 (11.6) 0.088
BMI, body mass index; CAP, community-acquired pneumonia; NHAP, nursing-home-
acquired pneumonia.
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Comorbidities
Comorbidity was very common in both groups but even more so
in patients with NHAP (97.1% vs 90.2%). Chronic respiratory
disease was less frequent whereas congestive heart failure,
cerebrovascular diseases, renal diseases and diabetes mellitus
were more frequent in patients with NHAP. The largest differ-
ence was in patients with cerebrovascular disease (66.1% vs
15.2% for the NHAP and CAP groups, respectively) (table 1).
Physical examination findings
Cough, sputum expectoration and chest pain were less common,
whereas confusion, low blood pressure and tachypnoea
were more common in the NHAP group compared with the
CAP group, indicating more severe pneumonia at presentation
(table 2).
Laboratory investigations
The main differences related to a higher frequency of anaemia
and leucocytosis, and to a higher thrombocyte count in the
NHAP group. However, mean C-reactive protein (CRP) was
lower (table 2).
Gas exchange
Arterial blood gas analysis was performed less frequently in
patients with NHAP compared with those with CAP (69.9% vs
78.1%, p<0.001).
Severity at presentation
The time from symptom presentation to hospital attendance
was around 2 days less in the NHAP group compared with the
CAP group. The proportion of patients classified as CRB-65 3e4
was around threefold higher in the NHAP group. However,
the rate of mechanical ventilation was similar (5.0% vs 4.8%)
(table 3).
Microbial aetiology
Diagnostic samples (package 1: blood cultures and urine antigen
testing, n¼1938 (80.4%) vs n ¼ 265 (63.5%), p<0.001; package 2:
blood cultures and urine antigen testing plus respiratory sample,
n¼933 (38.7%) vs n¼49 (11.8%), p<0.001) were retrieved less
frequently in the NHAP group compared with the CAP group.
The proportion of patients with a diagnostic investigation
able to identify a potential MDR pathogen (methicillin-resistant
S aureus (MRSA), enterobacteria, P aeruginosa) was significantly
lower in the NHAP group (n¼2350 vs n¼382, 91.4% vs 73.7%,
p<0.001).
The overall findings for microbial investigation were similar
(27.7% vs 29.7%). S pneumoniae was the most frequent pathogen
in both groups. Potential MDR pathogens such as enter-
obacteriaceae, P aeruginosa and S aureus were all very rare (<5%
for the total population and for patients with microbial
sampling). There were only minor differences in pathogens,
with Hinfluenzae and M pneumoniae being less frequent and S
aureus more frequent in patients with NHAP. In the NHAP
group, 11 of 12 patients with S aureus had central nervous
system (CNS) disorders. However, the absolute and relative
frequency of S aureus was minimal (n¼12, 2.3% of total popu-
lation, 3.1% of those with microbial sampling and 10.3% of
those with a pathogen determined), and of these, only two cases
were MRSA (table 4).
Antimicrobial treatment
Patients with NHAP received antimicrobial pretreatment less
frequently than patients with CAP (14.5% vs 18.9%). Mono-
therapy was more frequent and combination treatment less
frequent in patients with NHAP (22.8% vs 41.8% and 77.2% vs
57.2%). In addition, more patients with NHAP received ß-
lactams and fewer received macrolides (91.6% vs 86.9% and
16.6% vs 38.4%) and a change in antimicrobial treatment was
Table 2 Initial physical examination and laboratory findings
Variable
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Cough, n (%) 2266 (88.5) 425 (83.3) 0.001
Purulent sputum, n (%) 1394 (54.5) 210 (41.3) <0.001
Fever, n (%) 1461 (56.9) 294 (56.8) 0.955
Dyspnoea, n (%) 2072 (81.2) 424 (84.1) 0.123
Confusion, n (%) 374 (14.7) 243 (49.2) <0.001
Chest pain, n (%) 820 (33.2) 65 (16.4) <0.001
Severe hypotension*,
n (%)
542 (21.2) 154 (30.3) <0.001
Tachycardiay, n (%) 885 (34.7) 197 (38.6) 0.091
Tachypneaz, n (%) 310 (13.0) 83 (17.8) 0.007
Haemoglobin, g/dl
(median (IQR) (n))
13.2 (2.4) (2508) 12.6 (2.7) (507) <0.001
Anaemiax, n (%) 892 (35.6) 225 (44.4) <0.001
Complete blood count,
n (%)
2535 (99.7) 508 (99.8) 0.751
With differential, n (%) 716 (29.1) 110 (22.6) 0.004
Haematocrit, %
(median (IQR) (n))
39.0 (6.0) (2327) 38.0 (7.0) (474) <0.001
Platelets, /10
9
litre
(median (IQR) (n))
230 (123) (2491) 259 (143) (502) <0.001
Thrombopenia{, n (%) 243 (9.8) 33 (6.6) 0.025
Leucocytes, /10
9
litre
(median (IQR) (n))
12.4 (7.1) (2532) 13.5 (8.5) (507) 0.001
Leuocytosis**, n (%) 46 (1.8) 13 (2.6) 0.266
Leucopeniayy, n (%) 33 (1.3) 6 (1.2) 0.827
Lymphocytes, %
(median (IQR) (n))
10 (9) (710) 8.5 (8.4) (109) 0.392
CRP, mg/litre
(median (IQR) (n))
112 (180) (2478) 97 (149) (492) 0.023
BUN, mg/dl (median
(IQR) (n))
20.2 (15.5) (2163) 24.9 (23.9) (454) <0.001
*Systolic <90 mm Hg or diastolic #60 mm Hg.
yHeart rate >100/min.
zRespiratory rate $30/min.
x12 g/dl for women, 13 g/dl for men.
{Platelet count <140/10
9
litre.
**Leucocytes > 30/10
9
litre.
yyLeucocytes < 4/10
9
litre.
BUN, blood urea nitrogen; CAP, community-acquired pneumonia; CRP, C-re active protein;
NHAP, nursing-home-acquired pneumonia.
Table 3 Severity of pneumonia at admission
Variable
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Mechanical ventilation, n (%) 123 (4.8) 26 (5.0) 0.815
CRB-65 score, n (%)
000e
1e2 2165 (92.3) 327 (73.3) <0.001
3e4 181 (7.7) 119 (26.7) <0.001
Time from symptoms
until presentation, days
(median (IQR) (n))
4 (5) (1513) 2 (4) (226) <0.001
Length of stay, days
(median (IQR) (n))
11 (7) (2429) 10 (7) (436) <0.001
CAP, community-acquired pneumo nia; CRB-65, confusion, respiratory rate, blood pressure,
65 years and older; NHAP, nursing-home-acquired pneumonia.
134 Thorax 2012;67:132e138. doi:10.1136/thoraxjnl-2011-200630
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performed more frequently in patients with NHAP (42.4% vs
36.6%) (table 5).
Outcomes
Short-term mortality was nearly fourfold higher in the NHAP
group compared with the CAP group (26.6 vs 7.2%), and long-
term mortality nearly threefold higher (43.8% vs 14.6%) (table 5).
Death rates were still very high in patients with NHAP without
comorbidities, reaching 23.1% vs 2.6% for short-term mortality
and 30.8% vs 6.8% for long-term mortality.
Patients receiving enteral tube feeding (n¼103, 78.6% in the
NHAP group) had the highest mortality rates (30.7% short-term
and 56% long-term mortality).
Mortality rates according to aetiology in both groups are listed
in table 6. Short-term mortality in patients with CAP aged
$65 years was between 3.4% and 12.5%, with the highest rates
for S aureus, enterobacteriaceae, P aeruginosa and influenza A
whereas it was threefold to fourfold higher for all leading
pathogens in patients with NHAP. Similar rates were obvious in
long-term mortality, with S aureus being associated with an
extremely high mortality rate (80%).
DISCUSSION
The most important findings of this study were the following:
patients with NHAP presented with more severe pneumonia but
received the same frequency of mechanical ventilation and less
antimicrobial combination treatment; there were no clinically
relevant differences in aetiology and potential MDR pathogens
were very rare (<5%); short-term and long-term mortality for
NHAP was about fourfold and threefold higher than for CAP in
patients aged $65 years, however excess mortality was a general
pattern and not related to MDR pathogens.
Our approach to limit the comparison of patients to those
aged $65 years is an important methodological decision. In
a previous study from the CAPNETZ group comparing patients
aged <65 years and $65 years, those with NHAP showed
a fourfold increased mortality rate and an increased rate of gram-
negative bacillary infections compared with patients living in
the community (7.1% vs 3.7%, expressed as rate of pathogens
per cases with pathogens identified).
21
This difference, however,
is mainly a result of inflation by including a significant number
of younger patients. In view of the fundamentally different
epidemiology and prognosis of patients <65 years,
18
we argue
that the characteristics of NHAP can be assessed more
Table 4 Aetiology of pneumonia
Variable
Total population Cases with microbial sampling Cases with a pathogen determined
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Streptococcus
pneumoniae, n (%)
259/2569
(10.1)
38/518 (7.3) 0.053 259/2413 (10.7) 38/417 (9.1) 0.319 259/721 (35.9) 38/117 (32.5) 0.470
Mycoplasma
pneumoniae, n (%)
35/2569 (1.4) 1/518 (0.2) 0.024 35/2065 (1.7) 1/330 (0.3) 0.054 35/721 (4.8) 1/117 (0.9) 0.052
Legionella
spp., n (%)
102/2569 (4.0) 13/518 (2.5) 0.109 102/2243 (4.5) 13/357 (3.6) 0.439 102/721 (14.1) 13/117 (11.1) 0.376
Haemophilus
influenzae, n (%)
30/2569 (1.2) 1/518 (0.2) 0.042 30/2350 (1.3) 1/382 (0.3) 0.082 30/721 (4.2) 1/117 (0.9) 0.079
Enterobacteria, n (%) 67/2569 (2.6) 17/518 (3.3) 0.390 67/2350 (2.9) 17/382 (4.5) 0.093 67/721 (9.3) 17/117 (14.5) 0.080
Pseudomonas
aeruginosa, n (%)
23/2569 (0.9) 4/518 (0.8) 0.784 23/2350 (1.0)
91.4
4/382 (1.0) 73.7 0.900 23/721 (3.2) 4/117 (3.4) 0.837
Staphylococcus
aureus*, n (%)
18/2569 (0.7) 12/518 (2.3) 0.001 18/2350 (0.8)
91.4
12/382 (3.1) 73.1 <0.001 18/721 (2.5) 12/117 (10.3) <0.001
Moraxella
catarrhalis, n (%)
9/2569 (0.4) 1/518 (0.2) 0.566 9/2350 (0.4) 1/382 (0.3) 0.716 9/721 (1.2) 1/117 (0.9) 0.716
Influenza A, n (%) 59/2569 (2.3) 9/518 (1.7) 0.429 59/1786 (3.3) 9/312 (2.9) 0.700 59/721 (8.2) 9/117 (7.7) 0.857
Other pathogens,
n (%)y
57/2569 (2.2) 11/518 (2.1) 0.893
Aetiology is presented as pathogens per total population; pathogens per patients with microbial sampling; pathogens per patients with a pathogen determined. Enterobacteria comprise:
Escherichia coli , Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter spp., Proteus mirabilis, Serratia marcescens, Citrobacter spp., Marganella morganii.
*n¼2 accounted for methicillin-resistant S aureus.
yUndetermined as aetiology.
CAP, community-acquired pneumonia; NHAP, nursing-home-acquired pneumonia.
Table 5 Initial antimicrobial treatment and outcomes
Variable
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Prior antibiotic therapy*, n (%) 481 (18.9) 73 (14.5) 0.019
Initial antibiotic therapy, n (%) 2550 (99.3) 513 (99.0) 0.523
Monotherapy, n (%) 1476 (57.9) 396 (77.2) <0.001
Combination, n (%) 1067 (41.8) 117 (22.8) <0.001
Duration of antibiotic
therapy, days (median
(IQR) (n))
10 (6) (2342) 10 (6) (400) < 0.001
Change in antibiotic
therapy, n (%)
876 (36.6) 176 (42.4) 0.023
ß-Lactam antibiotics, n (%) 2216 (86.9) 470 (91.6) 0.003
Penicillins, n (%) 1258 (49.3) 280 (54.6) 0.030
Cephalosporins, n (%) 941 (36.9) 193 (37.6) 0.758
Carbapenems, n (%) 29 (1.1) 5 (1.0) 0.748
Macrolides, n (%) 980 (38.4) 85 (16.6) <0.001
Quinolones, n (%) 358 (14.0) 54 (10.5) 0.033
Tetracylines, n (%) 9 (0.4) 0 (0.0) 0.178
Glycopeptides, n (%) 6 (0.2) 0 (0.0) 0.271
Lincosamides, n (%) 15 (0.6) 4 (0.8) 0.614
Ketolides, n (%) 1 (0.0) 0 (0.0) 0.654
co-Trimoxazole, n (%) 6 (0.2) 2 (0.4) 0.531
Aminoglycosides, n (%) 8 (0.3) 4 (0.8) 0.123
Other antibiotics, n (%) 11 (0.4) 10 (1.9) <0.001
Died within 30 days, n (%) 172 (7.2) 105 (26.6) <0.001
Died within 180 days, n (%) 352 (14.6) 173 (43.8) <0.001
*Antibiotic therapy during the last 4 weeks.
CAP, community-acquired pneumonia; NHAP, nursing-home-acquired pneumonia.
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effectively by restricting the comparator to patients with CAP
aged $65 years. To avoid the impact of age, patients with NHAP
were also restricted to those aged $65 years.
Patients with NHAP were a clinically distinct group compared
with
those aged $65 years. They had a mean age of over
80 years, more frequently had congestive heart failure, cerebro-
vascular disease, renal disease and diabetes mellitus, indicating
that cardiovascular and neurological morbidity was the primary
underlying condition. Although these patients presented more
quickly after developing symptoms, initial pneumonia severity
was clearly higher according to symptoms at presentation and
CRB-65 scoring. Nevertheless, they obviously received less
attention and initial antimicrobial treatment was not as inten-
sive: blood gas analysis was performed around 10% less
frequently and antimicrobial combination treatment was
administered in only half of cases compared with patients
without NHAP. In addition, despite higher severity according to
CRB-65 scoring and the presence of severe hypotension,
mechanical ventilation was not given more frequently. However,
short-term and long-term mortality was far higher. All these
observations clearly show treatment restrictions due to
advanced age and severe disabling conditions in a significant
number of patients with NHAP. Unfortunately, we did not
record data on ‘do not resuscitate’ (DNR) orders. However,
although DNR orders are one form of treatment restriction,
other hidden restrictions (such as ‘do not re-evaluate extensively
in case of treatment failure’, ‘do not transfer to ICU [intensive
care unit]’, ‘do not ventilate’ etc) are usually not recorded.
Therefore, we argue that even recording DNR orders actually
underestimates the rate of treatment restrictions. We could not
identify clinically relevant differences in aetiologic patterns or
a clinically relevant higher frequency of potential MDR patho-
gens. In addition, mortality rates according to pathogens clearly
show that there is a threefold to fourfold higher mortality for
NHAP across all leading pathogens. This is strong evidence
against the hypothesis that excess mortality is related to inad-
equate treatment because of potential MDR pathogens not
covered by empirical treatment for CAP. Instead, as described by
others, MDR pathogens might be associated with severe
disablity.
22
Thus, the aetiologic patterns identified do not
account for the short-term and long-term excess mortality
observed in patients with NHAP.
We found that most cases of pneumonia caused by S
aureus
had CNS comorbidity, and that S aureus was associated with the
highest mortality. This is explained by the known risk for
pneumonia through S aureus in patients with CNS disorders,
mainly driven by aspiration.
23 24
Thus, a careful individual
assessment of risk for specific pathogens is clearly indicated in
every patient with NHAP.
For long-term mortality, an interesting observation was
a
lower mean CRP value in patients with NHAP. Lower CRP
values have recently been identified as an independent predictor
of long-term mortality. This probably reflects failure to mount
a sufficient immune response.
25
Our results are in line with two other important European
studies. In a British 18-month prospective cohort study of 437
patients admitted to hospital with CAP, 40 (9%) came from
nursing homes. Analysis of this small series yielded nearly
identical results to our study. Patients with NHAP were less
likely to have a productive cough or pleuritic pain but they were
more likely to be confused and had more severe disease. In-
hospital mortality was extremely high (53% vs 13% in patients
with CAP). S pneumoniae was the most common pathogen (55%
NHAP, 43% CAP). Atypical pathogens, enterobacteriaceae and S
aureus were uncommon. Poor functional status accounted for
the increased mortality in NHAP.
11
More recently, a Spanish
study including 150 consecutive cases of NHAP over a 10-year
period showed clinical characteristics comparable to those with
hospital-acquired pneumonia. However, microbial patterns and
mortality data of patients with NHAP were more similar to
those with CAP. Potential MDR pathogens were rare,
accounting for only 7% of pathogens.
12
Two recent studies from
Spain and the UK on HCAP confirmed this observation for both
NHAP and HCAP.
26 27
Likewise, the main findings of two Canadian studies were
very similar, including comorbidity patterns (more CNS disease,
fewer smokers and less pulmonary disease), less Hinfluenzae,
high mortality, and differences in treatment (less macrolide
treatment).
10
Mortality was very high but functional status
rather than different pathogen patterns was the main predictor
of death.
10 28
There was also clear evidence for treatment
restrictions.
28
Some US data indicate a different microbial pattern in
patients with NHAP. For example, El Solh et al found 17 of 88
(19%) pathogens of patients with NHAP and severe pneumonia
were MDR pathogens
21
; in another study, the authors found
anaerobic organisms more often in patients with NHAP and
empyema.
29
However, this seems to reflect a general trend in
older people rather than a specific finding in patients with
NHAP. Kaplan et al reported extremely high rates of enter-
obacteriaceae and P aeruginosa in a large population of patients
aged $ 65 years.
2
Accordingly, Koleff et al
13
listed exceedingly
high rates of MDR pathogens in patients with HCAP (including
many with NHAP) but also (to a lesser but still unusually high
Table 6 Short-term and long-term mortality according to underlying aetiologies
Pathogen
Short-term mortality Long-term mortality
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Patients with
CAP‡65 years
(n[2569)
Patients with
NHAP‡65 years
(n[518) p Value
Streptococcus pneumonia, n (%) 17/244 (7.0) 8/29 (27.6) <0.001 99/244 (11.9) 10/29 (34.5) 0.001
Mycoplasma pneumonia, n (%) 2/34 (5.9) 0/0 NC 5/34 (14.7) 0/0 NC
Legionella spp., n (%) 5/95 (5.3) 2/12 (16.7) 0.132 13/95 (13.7) 4/12 (33.3) 0.079
Haemophilus influenza, n (%) 1/29 (3.4) 0/1 (0.0) 0.850 1/29 (3.4) 0/1 (0.0) 0.850
Enterobacteriaceae, n (%) 7/67 (10.4) 4/11 (36.4) 0.022 11/67 (16.4) 5/11 (45.5) 0.027
Pseudomonas spp., n (%) 2/22 (9.1) 1/3 (33.3) 0.225 2/22 (9.1) 1/3 (33.3) 0.225
Staphylococcus aureus*, n (%) 2/17 (11.8) 4/10 (40.0) 0.088 6/17 (35.3) 8/10 (80.0) 0.025
Moraxella catarrhalis, n (%) 1/8 (12.5) 0/1 (0.0) 0.708 2/8 (25.0) 1/1 (100.0) 0.134
Influenza A, n (%) 5/55 (9.1) 1/8 (12.5) 0.759 6/55 (10.9) 2/8 (25.0) 0.263
*n¼1 accounted for methicillin-resistant S aureus.
CAP, community-acquired pneumonia; NC, not calculable; NHAP, nursing-home-acquired pneumonia.
136 Thorax 2012;67:132e138. doi:10.1136/thoraxjnl-2011-200630
Respiratory infection
group.bmj.com on September 13, 2015 - Published by http://thorax.bmj.com/Downloaded from
extent) in patients with CAP. The latter finding in particular
casts doubt on the validity of the microbiological investigation
in this study. Finally, it could not be shown that adhering to
guideline recommendations for treating patients with HCAP
improved outcomes compared with those for CAP.
30 31
Taken together, our data and the data reported in the literature
so far show that there is no convincing evidence to support
generally administering broad spectrum antimicrobial combi-
nation treatments comparable to those used for hospital-
acquired pneumonia to all patients with NHAP. Instead, the
initial antimicrobial coverage may still follow that recom-
mended in CAP guidelines after assessment of specific risk
factors for MDR on an individual basis. CNS disorders may
particularly be addressed since they predispose people to pneu-
monia through S aureus. Moreover, in patients with NHAP,
one cannot overestimate the importance of continuous careful
prognostic estimations and ethical decisions on treatment
aims and possible restrictions based primarily on patients’
preferences.
The strengths of this study include the multicentre prospec-
tive design over 8 years, which to the best of our knowledge is
unique in the literature. In addition, our population is one of the
largest reported in the literature so far. Nevertheless, some
potential limitations must be addressed. First, the proportion of
patients with an aetiology identified was low and did not exceed
30%. The proportion of samples from which a MDR pathogen
could be identified was significantly lower in patients with
HCAP, resulting in potential sampling bias. We tried to over-
come this limitation by reporting pathogen patterns according
to three different denominators. In particular, the rate of
‘pathogens per cases with microbial sampling’,reflecting the
likelihood of identifying the pathogen, allows us to estimate the
true incidence more accurately. This rate did not result in
different pathogen patterns. Thus, a systematic bias could only
result from a general failure to investigate specific groups of
patients at high risk of MDR pathogens not reflected in our
general pattern. Although this cannot be categorically excluded
in a potentially under-diagnosed population like those with
NHAP, it is highly improbable that patients with such severe
disabilities would have been subject to every treatment effort.
Second, the CAPNETZ population may include too few patients
with severe pneumonia. Therefore, the microbial patterns
presented here must be viewed with caution when patients with
HCAP are treated for severe pneumonia. Third, we did not assess
aspiration, which has been described as an important aetiology
in patients with NHAP and HCAP. However, the exact impli-
cations of aspiration in terms of microbial pathogens remain
unresolved.
22 32
Fourth, we did not directly measure functional
status. We recorded enteral tube feeding (ETF) as a surrogate,
and in fact, 78% of patients with ETF were patients with NHAP
and 15.6% of patients with NHAP had ETF. Direct comparisons
of mortality with other studies, however, should only be made
with caution. Evidently, we ignore the external validity of these
data for countries other than Germany. However, no country
should regard NHAP as a condition requiring an antimicrobial
treatment different from CAP prior to clear evidence that an
observed excess mortality is actually related to treatment fail-
ures in the presence of potential MDR pathogens. As a note of
caution, nursing homes that have patients with NHAP should
invariably be regarded individually for their potential to carry
a risk for the MDR pathogens.
In conclusion, the high excess mortality in our population
could
not be attributed to a microbial pattern different from
that of CAP (including an increased incidence of potential MDR
pathogens) but is likely to be a result of comorbidity and
management decisions as a result of pneumonia being regarded
as a terminal event related to advanced age and poor functional
status. The main challenges in the treatment of patients with
NHAP include a careful assessment of individual risk factors for
specific pathogens and a careful continuous estimation of
prognosis and patients’ preferences to set appropriate treatment
aims initially and during the course of the disease.
Acknowledgements We thank Dr Mark Woodhead for his help in editing the
manuscript.
Funding Bundesministerium fu
¨
r Bildung und Forschung (BMBF).
Competing interests None.
Ethics approval Central and local ethical committees (Ulm and local CAPNETZ
centres).
Contributors All authors contributed to the manuscript. Santiago Ewig was leader of
a local centre (Bonn, Bochum), analysed the data and revised the manuscript.
Benjamin Klapdor analysed the data and wrote the manuscript. Mathias Pletz analysed
the data. Gernot Rohde was leader of a local centre (Bochum) and analysed the data.
Hartmut Schu
¨
tte analysed the data. Tom Schaberg was leader of a local centre
(Rotenburg) and analysed the data. Torsten Bauer was leader of a local centre (Berlin)
and analysed the data. Tobias Welte is head of CAPNETZ, was leader of a local centre
(Hannover), and analysed the data.
Provenance and peer review Not commissioned; externally peer reviewed.
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Journal club
Improved survival in cystic fibrosis patients with
severely impaired lung function
A forced expiratory volume in one second (FEV
1
) less than 30% predicted has been accepted as
the threshold at which 50% of patients with cystic fibrosis (CF) survive 2 years or less.
However, this estimate, made in the early 1990s, does not take into account recent
developments in treatment. This cohort study aimed to re-evaluate the survival of CF patients
with severely impaired lung function.
Two hundred and seventy-six CF patients whose FEV
1
was first observed to be less than
30% predicted between 1990 and 2003 were included in the cohort. The patients were
followed up in 2-year subcohorts until 2007 and their survival was assessed. The authors
showed an important improvement in the average survival of CF patients with severely
impaired lung function. Median survival for patients who entered the cohort most recently
(2002e2003) was 5.3 years, more than four times that for those who entered the study in the
early 1990s, when median survival was 1.2 years. The authors observed a clear stepwise
improvement in survival from 1994 to 1997. This was concurrent with the introduction of
nebulised recombinant human DNase. A steady improvement in nutritional status also
occurred in the time period studied, and an increased risk of death was associated with a body
mass index below 19 kg/m
2
.
The survival of patients with CF and an FEV
1
less than 30% predicted has improved
markedly over the last two decades, with a median predicted survival of 5.3 years.
< George PM, Banya W, Pareek N, et al. Improved survival at low lung function in cystic fibrosis: cohort study from 1990 to
2007. BMJ 2011;342:1008.
Vishal Narwani
Correspondence to Vishal Narwani, Medical student, Royal Free Hospital, Pond Street, London NW3 2QG, UK;
vishal.narwani.10@ucl.ac.uk
Published Online First 4 May 2011
Thorax 2012;67:138. doi:10.1136/thoraxjnl-2011-200357
138 Thorax February 2012 Vol 67 No 2
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study
Germany: an 8-year prospective multicentre
Nursing-home-acquired pneumonia in
the CAPNETZ study group
Hartwig Schütte, Tom Schaberg, Torsten T Bauer, Tobias Welte and for
Santiago Ewig, Benjamin Klapdor, Mathias W Pletz, Gernot Rohde,
doi: 10.1136/thoraxjnl-2011-200630
2012 67: 132-138 originally published online November 5, 2011Thorax
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