Middle Tennessee Quantitative Research for Clinical Decision Making Paper Choose one published quantitative research study that has relevance to your PICOT

Middle Tennessee Quantitative Research for Clinical Decision Making Paper Choose one published quantitative research study that has relevance to your PICOT question.You must attach a PDF of the article you selected with your post. Read the article and answer the following questions in the Discussion Forum:

Include the citation for your article in APA format.

1. What key words did you use when conducting your search?

2. What was the study design?

3. Describe the level of the research design on the evidence hierarchy (use the Rating System for the Hierarchy of Evidence for Intervention/Treatment Questions in Melnyk and Fineout-Overholt, pg. 11)?

4. Why was the study done?

5. Describe the process of determining the validity, reliability, and applicability of this study design

6. What does this research mean for clinical practice and how did the findings of this research help to answer your PICOT question?

I will post the article that will be used to answer the questions along with the Rating system for the Hierarchy of Evidence Available online http://ccforum.com/content/8/6/R422
Research
December 2004
Open Access
Vol 8 No 6
Ventilator associated pneumonia: comparison between
quantitative and qualitative cultures of tracheal aspirates
Luis Fernando Aranha Camargo1, Fernando Vinícius De Marco2, Carmen Sílvia Valente Barbas1,
Cristiane Hoelz1, Marco Aurélio Scarpinella Bueno1, Milton Rodrigues Jr1,
Verônica Moreira Amado1, Raquel Caserta3, Marinês Dalla Valle Martino4, Jacyr Pasternak4 and
Elias Knobel5
1Assistant
Physican, Intensive Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brasil
Fellow, Intensive Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brasil
3Respiratory Therapist, Intensive Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brasil
4Microbiology Laboratory, Intensive Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brasil
5Head, Intensive Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brasil
2Postgraduate
Corresponding author: Luis Fernando Aranha Camargo, luis_camargo@einstein.com.br
Received: 28 April 2004
Critical Care 2004, 8:R422-R430 (DOI 10.1186/cc2965)
Revisions requested: 23 June 2004
This article is online at: http://ccforum.com/content/8/6/R422
Revisions received: 19 August 2004
© 2004 Camargo et al., licensee BioMed Central Ltd.
Accepted: 2 September 2004
This is an Open Access article distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/
licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is cited.
Published: 14 October 2004
Abstract
Introduction Deferred or inappropriate antibiotic treatment in ventilator-associated pneumonia (VAP)
is associated with increased mortality, and clinical and radiological criteria are frequently employed to
establish an early diagnosis. Culture results are used to confirm the clinical diagnosis and to adjust or
sometimes withdraw antibiotic treatment. Tracheal aspirates have been shown to be useful for these
purposes. Nonetheless, little is known about the usefulness of quantitative findings in tracheal
secretions for diagnosing VAP.
Methods To determine the value of quantification of bacterial colonies in tracheal aspirates for
diagnosing VAP, we conducted a prospective follow-up study of 106 intensive care unit patients who
were under ventilatory support. In total, the findings from 219 sequential weekly evaluations for VAP
were examined. Clinical and radiological parameters were recorded and evaluated by three
independent experts; a diagnosis of VAP required the agreement of at least two of the three experts.
At the same time, cultures of tracheal aspirates were analyzed qualitatively and quantitatively (105
colony-forming units [cfu]/ml and 106 cfu/ml)
Results Quantitative cultures of tracheal aspirates (105 cfu/ml and 106 cfu/ml) exhibited increased
specificity (48% and 78%, respectively) over qualitative cultures (23%), but decreased sensitivity
(26% and 65%, respectively) as compared with the qualitative findings (81%). Quantification did not
improve the ability to predict a diagnosis of VAP.
Conclusion Quantitative cultures of tracheal aspirates in selected critically ill patients have decreased
sensitivity when compared with qualitative results, and they should not replace the latter to confirm a
clinical diagnosis of VAP or to adjust antimicrobial therapy.
Keywords: bacterial pneumonia, qualitative evaluation, quantitative evaluation, tracheal aspirates, ventilator-associated pneumonia
BAL = bronchoalveolar lavage; cfu = colony-forming unit; ICU = intensive care unit; PSB = protected specimen brush; VAP = ventilator-associated
pneumonia.
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Critical Care
December 2004
Vol 8 No 6
Camargo et al.
Introduction
The incidence of nosocomial pneumonia in mechanically ventilated patients ranges from 9% to 68%, and mortality rates
range from 33% to 71% [1,2]. In the EPIC (European Prevalence of Infection in the Intensive Care) study [3], ventilatorassociated pneumonia (VAP) was the most frequent infection
acquired in the intensive care unit (ICU), accounting for 45%
of all infections in European ICUs.
The diagnosis of VAP is a challenge for the clinician because
the presentation is variable, and other causes of fever and
chest infiltrates may occur in these patients. Clinical/radiological evaluations provide the only criteria that permit timely diagnosis. Early institution of adequate antibiotic therapy is
associated with decreased mortality, at least in the more
severely ill patients. Culture results are currently used to guide
adjustment or withdrawal of antibiotic therapy rather than to
decide whether to treat. The practice of changing therapy with
culture results has resulted in reduced consumption of antibiotics. Conversely, studies have shown that over-treatment with
antibiotics may select organisms such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus [4,5].
The value of endotracheal aspirates for diagnosing VAP is
controversial, but there is a growing body of evidence showing
an important role for these cultures. Recent studies have consistently shown that outcome in VAP may not be influenced by
whether cultures are obtained by bronchoscopy or from tracheal aspirates collected at the bedside. Furthermore, a costeffectiveness analysis [6] strongly supported the employment
of tracheal aspirates in the management of VAP.
Although the use of tracheal aspirates in VAP management is
increasing, there are few data regarding the usefulness of
quantitative as opposed to qualitative cultures. Some studies
[7,8] suggested that quantitative cultures should be used in
order to avoid false-positive results, but little is known about
the sensitivity and specificity of quantitative culture findings in
severely ill patients who have previously received broad-spectrum antibiotics.
We conducted a prospective follow up of severely ill patients
in a general ICU with a high rate of antibiotic use in order to
evaluate the value of quantification of bacterial colonies in tracheal aspirates for diagnosing VAP.
Methods
Study protocol
This study was conducted between March 2000 and January
2001 in a 28 adult bed medical/surgical critical care unit at the
Hospital Israelita Albert Einstein – a major referral tertiary care
centre. The ethics committee of our institution granted
approval for this investigation.
R423
During the study period, every Monday morning all patients
under mechanical ventilation for at least 48 hours were examined to determine whether they had VAP by three well trained
intensivists and a respiratory therapist. We chose to evaluate
all ventilated patients irrespective of the presence of VAP
because on Mondays we routinely perform surveillance cultures of tracheal aspirates (in a search for multidrug-resistant
pathogens and to determine contact precautions for such situations). We also aimed to include both patients with and
without VAP based on clinical and radiological criteria.
The diagnosis of VAP was confirmed if there was agreement
between two of the three physicians using clinical/radiological
criteria. On the same day, the respiratory therapist also provided a description of the appearance (purulence) of the tracheal secretions. Endotracheal secretions were collected
using a standard procedure and endotracheal aspirates samples were sent for qualitative and quantitative culture. The
research team was blind to culture results, but the physicians
were aware of the patients’ antibiotic consumption when they
were evaluated.
Clinical characteristics were recorded at every evaluation (not
just at enrolment in the study).
Diagnosis of ventilator-associated pneumonia
For the purposes of the present study, VAP was diagnosed
when a patient on mechanical ventilation for at least 48 hours
developed a new or progressive pulmonary infiltrate on the
chest radiograph in association with at least two of the following findings: râles or dullness to percussion on chest examination; new onset of purulent sputum or change in sputum
character; decrease of at least 10% in arterial oxygen tension/
fractional inspired oxygen ratio; leucocytes in excess of
12,000/mm3 or under 4000/mm3; positive blood cultures or
pleural effusion cultures; and axilar temperature greater than
37.8°C or under 36.0°C in the absence of antipyretic treatment (excluding another site of infection).
Tracheobronchial aspirate samples and
microbiological processing
Tracheobronchial secretions were collected by the respiratory
therapist, following specimen collection guidelines, after tracheal instillation of 5 ml saline. The specimens were sent to the
laboratory and cultivated within 1 hour of collection. A dilution
of the tracheal aspirate was prepared and inoculated with a
calibrated loop on chocolate agar and MacConkey agar. After
overnight incubation in appropriate conditions, the plates were
interpreted according to quantification of growth [9,10]. Qualitative cultures were considered positive when the growth of
any micro-organism occurred and quantitative cultures were
considered positive when the growth of 105 colony-forming
units (cfu)/ml or more was observed. Sensitivity, specificity,
positive predictive value and negative predictive values for
qualitative and quantitative (105 cfu/ml and 106 cfu/ml)
Available online http://ccforum.com/content/8/6/R422
Table 1
Demographic data of the patients investigated
Parameter
Number of patients
Age (years)
Ratio of males to females (n)
APACHE II score
Value
106
66.6 ± 18.3
88/18
20.1 ± 6.5
Clinical category (n [%])
Medical
64 (60.3%)
Cancer
21 (19.8%)
Neurological
30 (28.2%)
Surgical
42 (39.7%)
APACHE, Acute Physiology and Chronic Health Evaluation.
cultures from tracheal aspirates were calculated according to
standard formulae. All samples were collected on the day of
clinical and radiological evaluation.
Results
A total of 106 patients were prospectively evaluated during
the study period. The mean age (± standard error) was 66.6 ±
18.3 years. A total of 88 patients (83.0%) were male and 18
(17.0%) were female. The mean Acute Physiology and
Chronic Health Evaluation II score was 20.1 ± 6.5. Medical
patients constituted the majority (60.38%) compared with surgical patients (39.62%; Table 1). Among medical patients, 30
(28.2%) were neurological and 21 (19.8%) were cancer
patients.
In these 106 patients, a total of 314 clinical evaluations were
conducted and endothracheal aspirates collected, corresponding to 42.3 ± 36.5 days (mean ± standard error) of
mechanical ventilation. In 95 of these evaluations the radiological or laboratory investigations for VAP were incomplete at the
time of clinical evaluation, and so these evaluations were
excluded. Therefore, a total of 219 evaluations in 106 patients
were included in the analysis.
Thirty-eight (17.4%) evaluations were classified as ‘with VAP’
in 33 patients and 181 (82.6%) were classified as ‘without
VAP’ in 73 patients (Table 2). The overall concordance
between the first two observers for a diagnosis of VAP in the
total population was high (94%). Within the VAP group, the
overall concordance between the first two observers was
86.9%.
Qualitative and quantitative analyses
For qualitative analysis, among all 219 evaluations, 168
(76.7%) yielded cultures that were positive for at least one
agent. In the VAP group, 31 of the 38 evaluations yielded positive cultures (81.6%). Thus, the sensitivity of qualitative cul-
tures of tracheal aspirates was 81% and the specificity was
23%. The likelihood ratio for a positive test was 1.05 and the
likelihood ratio for a negative one was 0.83. The positive predictive value was 18% and the negative predictive value was
86%.
For quantitative analysis, among the 219 evaluations, 117 had
? 105 cfu/ml in tracheal secretions (53.4%) and 49 had ? 106
cfu/ml (22.4%). In the VAP group, 25 of the 38 evaluations
had ? 105 cfu/ml (65.8%) and 10 of them had ? 106 cfu/ml
(26.3%). Thus, for 105 cfu/ml the sensitivity was 65% and the
specificity was 48%. The likelihood ratio of a positive test was
1.25 and the likelihood ratio of a negative test was 0.73. The
positive predictive value was 21% and the negative predictive
value was 87%. For 106 cfu/ml the sensitivity was 26% and
the specificity was 78%. The likelihood ratio of a positive test
was 1.18 and the likelihood ratio of a negative test was 0.95.
The positive predictive value was 20% and the negative predictive value was 83% (Table 3).
In the VAP group leucocytosis was present in 26 evaluations
(68.4%) and fever in 24 (63.1%), and purulent endotracheal
secretions were observed by the therapist in 22 (57.8%) evaluations. In four evaluations only (10.5%) was blood culture
positive for the same agent as was isolated in endotracheal
secretions (Table 4).
Overall, in 96.8% of evaluations patients were receiving at
least one antibiotic. Prescription of antibiotics for three or
more days before data collection was high (86.7%). The most
frequently administered antibiotics were glycopeptides
(49.7%), antifungals (42.4%), third-generation cephalosporins (39.2%), or carbapenem (34.2%; Table 5).
Considering all VAP episodes, the most frequently isolated
agents were Staphylococcus aureus (15.7%), P. aeruginosa
(15.7%) and Acinetobacter baumanii (7.3%). Fungi
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December 2004
Vol 8 No 6
Camargo et al.
Table 2
Clinical characteristics of the patients in the events investigated.
Parameter
Total evaluations (%)
Evaluations in VAP group (%)
Number of evaluations
219 (100%)
38 (100%)
Tracheostomy (n [%])
59 (26.9%)
10 (26.3%)
Atelectasisa (n [%])
13 (6.0%)
6 (15.7%)
Lung edemaa (n [%])
35 (16.0%)
9 (23.6%)
Lung contusiona (n [%])
6 (2.7%)
1 (2.6%)
Pleural effusiona (n [%])
21 (9,5%)
8 (21.0%)
Previous lung disease (n [%])
30 (13.6%)
6 (15.7%)
COPD
16 (7.3%)
3 (7.8%)
Cancer
11 (5.0%)
2 (5.2%)
Asthma
2 (0.9%)
1 (2.6%)
Pulmonary fibrosis
1 (0.4%)
None
Broncoaspiration (n [%])
12 (5.4%)
3 (7.8%)
Sepsis (n [%])
46 (21.0%)
14 (36.8%)
ARDS (n [%])
12 (5,4%)
3 (7.8%)
Renal failure (n [%]; creatinine >2.0 mg/dl)
91 (41.5%)
20 (52.6%)
Diabetes (n [%])
35 (16.0%)
5 (13.1%)
Chemotherapy (n [%])
13 (6.0%)
2 (5.2%)
Radiotherapy (n [%])
2 (0.9%)
None
Immunossupressants drugs (n [%])
5 (2.2%)
1 (2.6%)
AIDS (n [%])
3 (1.3%)
None
Renal transplantation (n [%])
5 (2.2%)
1 (2.6%)
Abdominal surgery (n [%])
32 (14.6%)
7 (18.4%)
Multiple trauma (n [%])
21 (9.5%)
3 (7.9%)
Neuromuscular blocking agents (n [%])
7 (3.1%)
7 (18.4%)
215 (98.0%)
38 (100%)
20 (9.1%)
1 (2.6%)
Central venous line (n [%])
Intracranial pressure monitoring (n [%])
aAccording
to clinical judgement. ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; VAP, ventilatorassociated pneumonia.
accounted for 13.3% of all agents isolated. In 18.4% of evaluations in the VAP group, no agent was recovered from the
endotracheal aspirates (Table 6).
Clinical observations
Considering the population as a whole, in 59 evaluations
(26.9%) patients had a tracheostomy. Stress ulcer prophylaxis
was present at 210 of the 219 evaluations (96%), with H2receptor blockers in 58.4%, proton pump inhibitors in 36.5%
and sucralfate in 0.9%. Sepsis was diagnosed in 46 (21%)
evaluations.
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Among the 38 evaluations classified as positive for VAP, tracheostomy was present in ten (26.3%). Previous lung disease
was observed in six (15.7%) events. Ulcer prophylaxis was
present in 100% of evaluations, with H2-receptor blockers in
22 (57.8%) and proton pump inhibitors in 16 (42.2%). Sepsis
was diagnosed in 14 (36.8%) evaluations.
Other clinical characteristics are listed in Table 2. A total of 31
(29.2%) patients died during their hospitalization: 11 (33.3%)
of the 33 patients in the VAP group and 20 (27.3%) of the 73
patients without VAP (not significant).
Available online http://ccforum.com/content/8/6/R422
Table 3
Qualitative and quantitative analysis
Parameter
Sensitivity
Qualitative
Quantitative
105 cfu/ml
106 cfu/ml
65%
26%
81%
Specificity
23%
48%
78%
Positive predictive value
18%
21%
20%
Negative predictive value
86%
87%
83%
Likelihood ratio of positive test
1.05
1.25
1.18
Likelihood ratio of negative test
0.83
0.73
0.95
cfu, colony-forming units.
Table 4
Diagnostic criteria for ventilator-associated pneumonia in order of occurrence
Diagnostic criteria
n (%)
Leukocytosis
26 (68.4%)
Fever
24 (63.1%)
Purulent tracheal secretion
22 (57.8%)
Decrease of at least 10% in PaO2/FiO2 ratio
16 (42.1%)
Rales or dullness to percussion on chest examination
9 (23.6%)
Leucopenia
4 (10.5%)
Blood positive cultures
4 (10.5%)
Hypothermia
2 (5.2%)
FiO2, fractional inspired oxygen; PaO2, arterial oxygen tension.
Discussion
VAP is the most frequent type of infection in ICU patients in
Europe and Latin America (almost half of all nosocomial infections) [3] and ranks second in US ICUs [11]. The attributable
mortality is higher in medical than in surgical patients, and
rates vary according to the case mix and aetiological agent
[12].
Inadequate or delayed antimicrobial treatment in VAP is an
established independent predictor of death [13]. According to
published data, changing an initial empirical treatment based
on subsequent culture results may have either a beneficial
effect (in terms of mortality, less antibiotic use, less days on
antibiotics) [14] or no effect in more severely ill patients [15].
For this reason, efforts must be directed at choosing adequate
empirical treatment as early as possible, which may be accomplished with a high degree of suspicion and adequate guidelines based on local antibacterial susceptibilities. In addition,
adhering to ideal pharmacological principles (choosing continuous as opposed to intermittent administration, adjustment for
renal and hepatic failures), reducing dosages when appropri-
ate, and shortening the duration of treatment are presently
standard of care for VAP.
In order to avoid any delay in instituting antibiotic treatment,
reliable diagnostic methods should be employed. Despite their
variable sensitivity and specificity [16], clinical/radiological
findings may currently be considered the best option, although
rapid tests, such as the percentage of infected leucocytes on
bronchial specimens, are promising in that they can provide
rapid confirmation [17]. Culture results for bronchial or tracheal samples may be available late in the course of an episode of VAP and should not be used to decide whether to
treat, especially in patients who are severely ill. On the other
hand, culture results should be used to adjust (narrow or
extend antibiotic spectrum) or withdraw empirical treatment –
a practice that has been shown to be beneficial, with no
increase in mortality, and that directs medical staff to seek
other unsuspected foci of infection [18].
Although bronchoscopic samples increase the degree of confidence that a diagnosis of VAP is correct [14], endotracheal
aspirates, despite their lack of consistency as a diagnostic tool
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Critical Care
December 2004
Vol 8 No 6
Camargo et al.
Table 5
Prescription of antimicrobials in all the events studied
Class of antimicrobial
Evaluations (n [%])
Glycopeptide
109 (49.7%)
Antifungical
93 (42.4%)
Third generation cephalosporin
86 (39.2%)
Carbapenem
75 (34.2%)
Clindamicin
34 (15.5%)
Quinolone
31 (14.1%)
Metronidazol
26 (11.8%)
Fourth generation cephalosporin
23 (10.5%)
Macrolides
23 (10.5%)
Total
212 (96.8%)
Table 6
Infectious agents isolated in the evaluations of patients with ventilator-associated pneumonia
Aetiological agents
Evaluations (n [%])
Gram-negative bacteria
15 (39.4%)
Gram-positive bacteria
11 (28.9%)
Negative cultures
7 (18.4%)
One or more agents
6 (15.7%)
Fungus
5 (13.3%)
Isolated agents
Staphylococcus aur…
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