Bronchoscopy in Nonresolving
pneumonia (VAP), the mortality rate in patients who had a rising score at 72 h, particularly if this score was ⱖ 20,was nearly 100% (Table 22).
Michael S. Niederman, MD, FCCP (CHEST 2000; 117:212S–218S)
Defining Pneumonia Resolution Abbreviations: APACHE ⫽ acute physiology and chronic
The resolution of nosocomial pneumonia can be de- health evaluation; CPIS ⫽ clinical pulmonary infection score; fined clinically or microbiologically, but presumably a PSB ⫽ protected-specimen brush; VAP ⫽ ventilator-associated clinical nonresponse will the prompt consideration of bronchoscopic evaluation. Definable clinical end pointsinclude the following: resolution of all signs and symptoms of infection; improvement in all signs and symptoms of in evaluating and managing patients with nosocomial infection; slow or delayed resolution of signs and symp- pneumonia who are not responding to initial antibiotic toms; relapse after initial infection (presumably represent- therapy. This discussion examines whether the informa- ing recurrent infection); progression of signs and symp- tion provided by bronchoscopy has value in this setting, as toms (rapid or gradual); superinfection that clinically well as whether the concept of using bronchoscopy for the resembles delayed resolution, progression, or relapse, but nonresponding patient is a logical one.
is characterized by these clinical findings in conjunction Importantly, serial bronchoscopy is generally per- with the microbiological finding of an organism not formed while the patient is receiving antibiotic therapy.
present at the onset of pneumonia; and, finally, death due Such therapy can reduce the yield and accuracy of quan- to unresolved infection, the ultimate outcome of a lack of titative cultures of respiratory secretions. The presump- response to therapy. Measurements to define these clini- tion for using serial cultures in the nonresponding patient cal end points include assessment of the following: fever, is that bacteria are present that have not been eliminated sputum purulence, leukocytosis, oxygenation, radiographic by currently administered antibiotics. Moreover, these improvement, duration of organ failure, duration of me- organisms can be identified early enough so that changes chanical ventilation, and need for changes in antibiotic in therapy will improve the outcome in these patients.
One way to assess the clinical resolution of pneumonia is to combine a number of clinical findings into a scoring Can Clinical Features Be Used to Predict system, such as the clinical pulmonary infection score the Likelihood of a Nonresponse to (CPIS) of Pugin et al30 Using a modification of this system, Garrard and A'Court131 measured the CPIS on a dailybasis in 83 patients with nosocomial pneumonia. The CPIS A number of clinical findings have been identified as was used to diagnose pneumonia if the score was ⱖ 6 risk factors for mortality from nosocomial pneumonia. If a (highest possible score, 10), based on the assessment of patient has a multitude of these features and is not five variables, each with a score range of 0 to 2. These responding to initial antibiotic therapy, the nonresponse variables were the following: temperature, WBC count, may be the inevitable outcome of serious systemic illness purulence of secretions, oxygenation, and extent of radio- and comorbidity. Serial bronchoscopic data are unlikely to graphic infiltrates. The CPIS was observed to increase reduce the expected high mortality rate in such a popula- progressively from a baseline value of ⬍ 6 to a value of ⬎ 6 tion. Such risk factors, identified in multivariate analysis, over the 2 days preceding the day of diagnosis and included the following: prolonged duration of ventilation, initiation of antibiotic therapy.30 Once therapy was begun, coma on admission, creatinine levels ⬎ 1.5 mg/dL, and the CPIS fell gradually over the next 9 days, generally transfer to the ICU from another ward67; the presence of dropping below 6 by the fifth day. When the CPIS did not certain high-risk pathogens, abnormal bilateral radio- fall, clinical deterioration was usually due to infection with graphic findings, inappropriate initial therapy, age ⬎ 60 years, and an ultimately terminal underlying condition62; Resolution also can be defined by bacteriologic end shock, inappropriate initial therapy, and rapidly fatal un- points that are based on the assessment of serial qualitative derlying illness44; prior antibiotic therapy128; infection with cultures of respiratory secretions. Microbiological eradica- a resistant organism, particularly Pseudomonas aeruginosa tion is defined by the elimination of the original pathogen or Staphylococcus aureus129; multiple systems organ fail- from the culture of the secretion, usually sputum. Persis- ure, nonsurgical primary diagnosis, late-onset infection tence is defined by a failure to eliminate the organism.
with a high-risk pathogen, and prophylaxis for intestinal Reinfection refers to elimination of the organism, followed bleeding with a pH-elevating agent.127 More recently, by its return, and superinfection refers to the appearance Rello et al130 observed that if acute physiology and chronic of a new organism in the culture. Quantitative microbiol- health evaluation (APACHE) II scores are followed seri- ogy cultures of respiratory secretions obtained broncho- ally after the onset of P aeruginosa ventilator-associated scopically or nonbronchoscopically also can be used todefine the resolution of nosocomial pneumonia.
*From the Division of Pulmonary and Critical Care Medicine, Garrard and A'Court131 used serial quantitative cultures Winthrop University Hospital, Mineola, NY.
of nondirected, nonbronchoscopic lung specimens ob- Evidence-Based Assessment of Diagnostic Tests for Ventilator-Associated Pneumonia Table 22—Studies Defining Risk Factors for Mortality in VAP*
Univariate Predictors No. of Patients With NP Resistant Bacteria Risk Craven et al67/1986 Duration of Vent, creatinine ⬎ 1.5, respiratory failure, and Celis et al62/1988 120 (84 resp failure) 36.6 (47.6 if resp failure) Age ⬎ 60, service UF illness, High-risk organism prior ABTC, high-risk organism, bilateral infiltration, shock, Rx, Age ⬎ 60 yr Torres et al44/1990 UF illness, inappropriate Rx, prolonged ICU, shock, Rello et al47/1991 20/91 with Haemophilus 30 (none died from influenzae (vent) H influenzae Rello et al128/1993 Age ⬎ 45 yr, corticosteroid Yes, high-risk pathogen Rx, shock, VAP onset ⬎ 9 days, COPD, prior ABTC Malangoni et al129/1994 2/3 failures developed resistance during Rx,ESP withP aeruginosa *Rx ⫽ treatment; ABTC ⫽ antibiotic; UF ⫽ ultimately fatal; NP ⫽ nosocomial pneumonia; vent ⫽ receiving ventilation; resp ⫽ respiratory.
tained by lavage from patients receiving ventilation who sodes in 30 patients in whom there was clinical suspicion have nosocomial pneumonia and correlated the findings of pneumonia and found borderline results (102 to 103 with serial measurement using the CPIS. Using a 14-gauge cfu/mL) with the initial cultures. Patients had repeat tracheal suction catheter with 20 mL normal saline solu- bronchoscopy within 72 h if the suspicion of pneumonia tion, the authors evaluated 89 episodes of nosocomial in 83 persisted and if patients were not given antibiotics. In 12 patients by using alternate-day sampling and quantitative episodes, the same organism was isolated on the repeat cultures of respiratory secretions. Culture counts rose bronchoscopy, but the concentration was then ⬎ 103 during the 2 days preceding the clinical onset of pneumo- cfu/mL and antibiotics were given. In 22 episodes, pneu- nia and fell rapidly with the initiation of therapy. Patients monia was excluded as a diagnosis. The mortality rate in showing a clinical response to therapy had a rapid fall in the eight patients having a positive culture finding on colony counts by 24 h, in most instances, and usually no repeat bronchoscopy was 75% (6 patients), which was later than 48 to 72 h, unless there was a lack of response significantly higher than the mortality rate in the 18 to treatment. The patients who had no response to patients with a negative culture finding on repeat bron- treatment usually had P aeruginosa pneumonia; these choscopy (22%; 4 patients; p ⬍ 0.04). Serial bronchoscopy patients had a persistence of colony counts of ⬎ 10,000 can identify pneumonia patients who cannot contain a cfu/mL and a high mortality rate. Serial quantitative bacterial challenge or who had a prior false-negative cultures correlated well with clinical response and mortal- culture finding. The high mortality rate may be related to ity, with the counts of those patients responding falling the delayed initiation of antibiotic therapy after an initial rapidly. This microbiological pattern was analogous to the false-negative culture result.
clinical findings, as reflected by the CPIS. Nonresponse to Montravers et al32 studied the results of cultures with therapy was not predicted more accurately by microbio- specimens gathered using the serial PSB method in 76 logical findings than by clinical findings. While a microbi- patients with VAP. A clinical suspicion of pneumonia in ological nonresponse could be defined at 24 to 72 h, the enrolled patients was confirmed by a bacteria count of recognizing a clinical nonresponse generally took longer.
ⱖ 103 cfu/mL in a sample. The clinicians' initial antibiotic Serial bronchoscopy also has been used to determine choice was modified on the basis of bronchoscopy results.
whether a patient is not responding to initial therapy, and All patients had a second bronchoscopy 3 days after entry if so, why. Dreyfuss et al60 collected data using a serial into the study. The clinical outcome and serial microbio- protected-specimen brush (PSB) technique for 34 epi- logical data were compared, with clinical outcomes classi- CHEST / 117 / 4 / APRIL, 2000 SUPPLEMENT Table 23—Studies of Repeat Bronchoscopy During the Course of Suspected VAP*
When Bronchoscopy Repeated Impact on Outcome Montravers et al32/1993 PSB after 3 d therapy Defining bacteriologic failure at day 3 16 with ⬍ 103 cfu/mL did not prevent high mortality 9 with ⬎ 103 cfu/mL 7% failure rate if sterile at day 3 56% failure ifrepeat ⬎ 103 cfu/mL Dreyfuss et al60/1993 Mean, 2.7 d after first therapy 12 had pneumonia on repeat Higher mortality in group with ⫹ repeat bronchoscopy, delay in adequate Rx *See Table 22 for abbreviation.
†With 34 episodes. PSB method yielded borderline cultures on first test; there was no effective RX for these organisms.
fied as improved, relapse, or failure. Bacteriologic out- study), the mortality rate was 38%; for those with inade- comes were grouped by the eradication of the pathogen, quate therapy, the mortality rate was 91%.
the continued isolation of the pathogen, or the emergence After bronchoscopy was completed, 42 of the 65 pa- of a new pathogen. Any pathogens present on the repeat tients (65%) received adequate therapy and the other 23 bronchoscopy were noted as being at low (ie, ⬍ 103 received inadequate therapy, but the mortality rate in the cfu/mL) or high (ie, ⱖ 103 cfu/mL) concentrations.
two groups was comparable. Similarly, outcomes did not In the study by Montravers et al32, 51 patients had improve after bronchoscopic data were known, although sterile pulmonary secretions by day 3, 16 patients had almost all patients received adequate therapy at that time.
persistent low-level infection, and 9 patients had persistent The generalizability of these findings is limited by the very high-level infection (Table 23). Clinical improvement was high mortality rates reported by Luna et al33 in all patient seen in 96% of those with microbiological eradication, in groups. Bronchoscopy may identify organisms that are not 81% of those with persistent low-level infection, and in responding to the initial antibiotic regimen. Whether this 44% of those with persistent high-level infection information will improve the outcome is uncertain but (p ⬍ 0.01).
needs to be formally investigated.
Follow-up bronchoscopy can be used to identify pa- Recently Rello et al132 studied 113 patients with VAP, tients with a clinical nonresponse to therapy. The highest 100 of whom (88%) had an organism identified by bron- rates of clinical nonresponse occurred in the patient whose choscopy. Based on these data, 27 patients had initial follow-up bronchoscopy showed a high concentration of inadequate antibiotic therapy. This group had a signifi- bacteria. The finding of persistent bacterial infection can cantly higher mortality rate than those receiving adequate be used to predict a poor outcome, but there are no data therapy (37% vs 15.4%, respectively). However, when to suggest that interventions based on these results will antibiotic therapy was changed, based on bronchoscopic improve patient outcome.
data, 17 of the 27 patients (63%) had clinical resolution,and 10 of those 17 patients (59%) survived and weredischarged. Thus, bronchoscopically directed changes in Are Serial Bronchoscopy Data Likely to therapy may have been beneficial, although aspiration Help the Nonresponding Patient? cultures may have provided similar data.
The potential limitations of serial bronchoscopy include The results of the study by Montravers et al32 suggest the following: (1) information may become available too that data taken from serial PSB sampling provide a late; (2) the bacteriologic information could be provided microbiological explanation for clinical nonresponse.
by simpler, more readily available methods, such as tra- However, it is uncertain whether this information leads to cheal aspiration culture; and (3) repeat testing usually improved outcome. The outcome in patients with nosoco- isolates highly resistant organisms that would not be mial pneumonia may be dictated by the efficacy of initial eliminated by changes in antibiotic therapy. The last therapy. Bronchoscopic data may be available too late to limitation was suggested by Garrard and A'Court,131 who influence the course of illness.
found that nonresponding patients had persistent high- Luna et al33 used bronchoscopy with quantitative BAL level infections with organisms that are difficult to eradi- and found an etiologic pathogen in 65 of 132 patients cate, such as P aeruginosa. Similarly, Silver et al133 de- (49%) who had a clinical diagnosis of nosocomial pneu- scribed the phenomenon of recurrent infection with monia. More than half of the patients were already P aeruginosa in critically ill patients. Silver et al133 docu- receiving antibiotics for either community-acquired pneu- mented that recurrent infection with this organism is monia or a previous episode of nosocomial pneumonia. In common (ie, found in 10 of 20 patients [50%] who this group, 50 of the 65 patients (77%) received immediate survived a first episode of P aeruginosa pneumonia) and antibiotic therapy, prior to the bronchoscopy, which was often fatal (mortality rate, 60% for those patients with performed within 24 h after the clinical diagnosis of recurrent P aeruginosa pneumonia vs 10% for those pneumonia. For 16 of 65 patients (25%) whose initial therapy was adequate (as defined by BAL bacteriology Souweine and colleagues36 confirmed that bronchos- Evidence-Based Assessment of Diagnostic Tests for Ventilator-Associated Pneumonia copy can identify the bacteria responsible for nonresponse infection during the acute respiratory distress syndrome.
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Targeted nutritional intervention für down-syndrom

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Microsoft word - lidia brunetto's phd thesis.doc

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