Mustafa El-Ebiary

Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies

BACKGROUND A study was undertaken to assess the diagnostic value of different clinical criteria and the impact of microbiological testing on the accuracy of clinical diagnosis of suspected ventilator associated pneumonia (VAP). METHODS Twenty five deceased mechanically ventilated patients were studied prospectively. Immediately after death, multiple bilateral lung biopsy specimens (16 specimens/patient) were obtained for histological examination and quantitative lung cultures. The presence of both histological pneumonia and positive lung cultures was used as a reference test. RESULTS The presence of infiltrates on the chest radiograph and two of three clinical criteria (leucocytosis, purulent secretions, fever) had a sensitivity of 69% and a specificity of 75%; the corresponding numbers for the clinical pulmonary infection score (CPIS) were 77% and 42%. Non-invasive as well as invasive sampling techniques had comparable values. The combination of all techniques achieved a sensitivity of 85% and a specificity of 50%, and these values remained virtually unchanged despite the presence of previous treatment with antibiotics. When microbiological results were added to clinical criteria, adequate diagnoses originating from microbiological results which might have corrected false positive and false negative clinical judgements (n = 5) were countered by a similar proportion of inadequate diagnoses (n = 6). CONCLUSIONS Clinical criteria had reasonable diagnostic values. CPIS was not superior to conventional clinical criteria. Non-invasive and invasive sampling techniques had diagnostic values comparable to clinical criteria. An algorithm guiding antibiotic treatment exclusively by microbiological results does not increase the overall diagnostic accuracy and carries the risk of undertreatment.

Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study

In contrast to the healthy population, distal airway bacterial colonization may occur in patients with chronic lung diseases, who often have altered pulmonary defences. However, the information dealing with this issue is insufficient and is based mainly on nonspecific samples, such as sputum cultures. Using quantitative cultures of bronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples, we studied the bacterial colonization of distal airways in 16 healthy subjects, 33 patients with bronchogenic carcinoma, 18 with chronic obstructive pulmonary disease (COPD), 17 with bronchiectasis, and 32 with a long-term tracheostomy due to laryngeal carcinoma. All patients were without exacerbation, and free from antibiotic treatment at least 1 month before the study protocol. Thresholds for quantitative cultures to define colonization were > or = 10(2) colony-forming units (cfu) x mL(-1) for PSB and > or = 10(3) cfu x mL(-1) for BAL. Only one healthy subject was colonized by a potential pathogenic microorganism (PPM) (Staphylococcus aureus 4x10(2) cfu x mL(-1) in a PSB culture). Colonization was observed in 14 (42%) bronchogenic carcinoma patients (19 non-PPMs, and 10 PPMs); in 15 (83%) COPD patients (22 non-PPMs and 7 PPMs); in 15 (88%) bronchiectasis patients (20 non-PPMs and 13 PPMs); and in 15 (47%) long-term tracheostomy patients (5 non-PPMs and 13 PPMs). The two most frequent non-PPMs isolated in all groups studied were Streptococcus viridans and Neisseria spp. Haemophilus spp., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were the most frequent PPMs isolated in bronchogenic carcinoma, COPD, bronchiectasis and long-term tracheostomized patients, respectively. Pseudomonas aeruginosa colonization was infrequent in all the groups. Our results show that distal airway bacterial colonization is a frequent feature in stable patients with chronic lung diseases and also in patients with long-term tracheostomy. However, the pattern of colonization differs among groups studied. The knowledge of different colonization patterns may be important for future antibiotic prophylactic strategies and for the empirical antibiotic regimens when exacerbations occur in these patients.

Cytokine expression in severe pneumonia: a bronchoalveolar lavage study.

OBJECTIVE To assess the cytokine expression (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, and IL-6) in severe pneumonia, both locally (in the lungs) and systemically (in blood). DESIGN Prospective sequential study with bronchoalveolar lavage (BAL) and blood sampling. SETTING Six-bed respiratory intensive care unit of a 1,000-bed teaching hospital. PATIENTS Thirty mechanically ventilated patients (>48 hrs) were allocated to either the pneumonia group (n = 20) or a control group (n = 10). INTERVENTIONS Protected specimen brush and BAL samples for quantitative cultures, and serum and BAL fluid TNF-alpha, IL-1beta, and IL-6 levels were measured on days 1, 3, and 7. In the control group, the procedure was done on day 1 only. MEASUREMENTS AND MAIN RESULTS Serum TNF-alpha levels were significantly higher in patients with pneumonia compared with controls (35 +/- 4 vs. 17 +/- 3 pg/mL, respectively, p = .001). IL-6 levels in serum and BAL fluid were higher in pneumonia than in control patients (serum, 837 +/- 260 vs. 94 +/- 35 pg/mL, respectively, p = .017; BAL fluid, 1176 +/- 468 vs. 234 +/- 83 pg/mL, respectively, p = .05). On days 1, 3, and 7 in patients with pneumonia, IL-1beta levels turned out to be higher in BAL fluid than in serum (71 +/- 17 vs. 2 +/-1 pg/mL on day 1; 49 +/- 8 vs. 6 +/- 2 pg/mL on day 3; and 47 +/- 16 vs. 3 +/- 2 pg/mL on day 7 for BAL fluid and serum, respectively, p < .05). No significant correlation between BAL fluid cytokine levels and lung bacterial burden was shown in presence of antibiotic treatment. Although no clear relationship was found between BAL fluid and serum cytokines and mortality, there was a trend toward higher serum IL-6 levels in nonsurvivors (1209 +/- 433 pg/mL) with pneumonia compared with survivors (464 +/- 260 pg/mL). In addition, serum TNF-alpha and IL-6 correlated with multiple organ failure score (r2 = .36, p = .004 for both) and with lung injury score (r2 = .30, p = .01, and r2 = .22, p = .03, for TNF-alpha and IL-6, respectively). CONCLUSIONS The present study describes the lung and systemic inflammatory response in severe pneumonia. The lung cytokine expression seems to be independent from the lung bacterial burden in the presence of antibiotic treatment. Because of the limited sample size, we did not find a clear relationship between serum and BAL fluid cytokine levels and outcome.

Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU

Patients with haematological malignancies developing severe pulmonary complications have a poor outcome, especially after bone-marrow transplantation (BMT). We studied the aetiology, the yield of different diagnostic tools, as well as the outcome and prognostic factors in the corresponding population admitted to our respiratory intensive care unit (RICU). Overall, 89 patients with haematological malignancies and pulmonary complications treated within a 10 yr period were included. The underlying malignancies were predominantly acute leukaemia and chronic myeloid leukaemia (66/89, 74%). Fifty-two of 89 (58%) patients were bone marrow recipients. An aetiological diagnosis could be obtained in 61/89 (69%) of cases. The aetiology was infectious in 37/89 (42%) and noninfectious in 24/89 (27%). Blood cultures and cytological examinations of bronchoalveolar lavage fluid were the diagnostic tools with the highest yield (13/43 (30%) and 13/45 (29%) positive results, respectively). Necropsy results were coincident with results obtained during the lifetime in 43% of cases with infectious and 60% with noninfectious aetiologies. Overall mortality was 70/89 (79%), and 47/52 (90%) in transplant recipients. The requirement of mechanical ventilation, BMT, and an interval <90 days of BMT prior to ICU admission were independent adverse prognostic factors. The outcome in this patient population was uniformly poor. It was worst in bone marrow recipients developing pulmonary complications <90 days after transplantation and requiring mechanical ventilation. Decisions about intensive care unit admission and mech-anical ventilation should seriously consider the dismal prognosis of these patients.

Utility of Selective Digestive Decontamination in Mechanically Ventilated Patients

Nosocomial pneumonia is a frequent complication of prolonged mechanical ventilation [1-3]. Oropharyngeal and gastric colonization, because of potentially pathogenic microorganisms and their subsequent aspiration to the lower airways, play a substantial role in the pathogenesis of ventilator-associated nosocomial pneumonia [4, 5]. Selective digestive decontamination has been widely used as a prophylactic regimen for ventilator-associated nosocomial pneumonia. The first to describe this complication, Stoutenbeek and colleagues [6] suggested that the best combination for preventing nosocomial pneumonia was the use of topical nonabsorbable antibiotics in the oropharynx and stomach together with systemic antibiotics. Most studies have shown a substantial decrease in the carriage of gram-negative bacilli of the upper and lower airways and also in the incidence of nosocomial pneumonia [7, 8], and a few studies have shown a substantial decrease in the overall mortality rate [9-11]. Several important considerations in most of the studies still make selective digestive decontamination a controversial issue. First, several studies were not randomized or used historical controls [6, 12-19]. Second, most of the randomized studies used only nonspecific methods to diagnose nosocomial pneumonia [9, 11, 20-28]. Finally, despite the apparent decrease in the incidence of nosocomial pneumonia, mortality did not change in most of the studies [12-28], including two recent randomized and double-blind studies [29, 30] of a large population sample of patients in an intensive care unit. We did a randomized, double-blind study of selective digestive decontamination in a general population of patients requiring mechanical ventilation. The main end points of this study were to assess the effect of selective digestive decontamination in decreasing nosocomial pneumonia and mortality. Additional end points of this study were to determine the effect of selective digestive decontamination on the morbidity (length of stay and duration of mechanical ventilation) and the mortality rate. Methods Patients The study was done in the Respiratory Intensive Care Unit of the Hospital Clinic of Barcelona, Spain, a 1000-bed teaching hospital, during a period of 12 months. All mechanically ventilated patients admitted to the respiratory intensive care unit and expected to remain intubated for more than 3 days were included in the study. The only exclusion criterion was the presence of immunosuppression (human immunodeficiency virus [HIV] infection, HIV-related diseases, patients who received transplants, and patients treated with antineoplastic chemotherapy). Patients who were extubated or who died before receiving 72 hours of selective digestive decontamination or placebo were also excluded from the analysis. Study Design Patients were randomly allocated to either the selective digestive decontamination or the placebo group. The randomization was done using a computer-generated table, and the patients were enrolled consecutively. Severity of illness was evaluated by means of the Simplified Acute Physiologic Score after randomization. The authors of the study were blinded in the recovery of the results. The study ended after extubation or death of the patient in the intensive care unit. Administration of Antibiotics After samples for the bacteriologic assessment were obtained, antibiotics were administered for selective digestive decontamination. An aqueous suspension of 10 mL containing polymyxin E, 100 mg (Dumex; Dumex Limited, Denmark); tobramycin, 80 mg (Tobradistin; Dista SA, Madrid, Spain); and amphotericin B, 500 mg (Fungizona; Squibb Industria Farmaceutica SA, Madrid) was administered through a nasogastric tube to patients in the selective digestive decontamination group. Carboxymethyl-cellulose with pectin and with gelatin (0.5 mL, Orabase; Drogfesa, Mollet del Valles, Spain) containing polymyxin E, tobramycin, and amphotericin B, at 2% concentration, was applied four times a day. In the placebo group, an aqueous suspension of Maxipro (Scientific Hospital Supplies Limited, Liverpool, United Kingdom) and Orabase, both colored with tartrazine, were administered through the nasogastric tube and in the oropharynx at the same dosage as for patients who received selective digestive decontamination. Systemic Antibiotic and Stress Ulcer Prophylaxis Patients were treated with 2 g of intravenous cefotaxime four times a day (Primafen, Hoechst Iberica SA, Barcelona, Spain) for the first 4 days of mechanical ventilation if they did not have infection on admission. Infected patients who were admitted to the intensive care unit received other parenteral antibiotics according to clinical decisions. Prophylaxis for stress ulcers was done using 1 g of sucralfate every 4 hours (Urbal; Merck-Igoda SA, Mollet del Valles) through a nasogastric tube, except in patients with paralytic ileus or with upper gastrointestinal bleeding, who were treated with 50 mg of intravenous ranitidine, four times a day (Zantac; Glaxo SA-Allen Farmaceutica SA, Madrid). Bacteriologic Assessment Endotracheal aspirates, pharyngeal swabs, and gastric juice samples were obtained three times a week for quantitative cultures. Endotracheal aspirate samples were obtained by means of sterile tubes (Mocstrap; Productes Clinics, SA, La Llagosta, Barcelona). Samples obtained were diluted and homogenized in distilled water to 1/2 concentration using a vortex-style shaker (Reax 2000; Heidolph, Germany) and were rediluted in distilled water to 1/20 and 1/200 concentrations. Pharyngeal swabs were obtained using sterile swabs with Amies transport media (Eurotubo; Industrias Aulabor SA, Barcelona), were homogenized in 1 mL of distilled water, and were diluted to concentrations of 1/10, 1/102, and 1/103. Gastric juice samples were obtained by aspiration through a nasogastric tube using a sterile feeding syringe. The pH was determined in all the samples using paper indicators (Acilit, pH 0 to 6 and Spezialindikator, pH 6.5 to 10; Merck, Darmstadt, Germany). The samples were homogenized using a vortex-style shaker and were diluted in distilled water to concentrations of 1/10 and 1/100. All samples were plated on the following agar media: blood; chocolate; McConkey-2; buffered, charcoal, and yeast extract (BCYEa); Sabouraud-dextrose; Sabouraud with nalidixic acid; and blood with nalidixic acid. If negative, the plates were discarded after 5 days of testing for aerobic bacteria, after 10 days of testing for Legionella and anaerobic bacteria, and after 4 weeks of testing for fungi. If positive, counts of colony-forming units per milliliter and identification using standard methods [31] were done for the microorganisms. Definitions Potentially pathogenic microorganisms were defined [32] as those causing infection in a person with impaired defense mechanisms. They can be classified into community microorganisms, which cause infections in previously healthy persons with intact carriage defense, and nosocomial microorganisms, which cause infections in persons with impaired carriage defense. Colonization was defined as the isolation of the same strain of a potentially pathogenic microorganism from at least two consecutive surveillance samples in any concentration. The clinical diagnosis of pneumonia was based on the presence of all of the following criteria: new or progressive pulmonary radiologic infiltrate or both for 48 hours or more, purulent tracheal secretions, temperature of 38.5 C or more, and leukocytosis ( 12 109/L) or leukopenia ( 4 109/L). The diagnosis of pneumonia was confirmed by the isolation of a potentially pathogenic microorganism in a protected specimen brush sample in concentrations of 103 CFU/mL or more or in a bronchoalveolar lavage sampling in concentrations of 104 CFU/mL or more [33]. We defined definite pneumonia when all the clinical criteria and one bacteriologic criterion were present or by the presence of histologic signs of pneumonia at autopsy. Probable pneumonia was defined when only clinical criteria were present. Primary endogenous pneumonia was diagnosed when pneumonia developed within the first 4 days of mechanical ventilation and when etiologic microorganisms were isolated previously or concomitantly in pharyngeal swabs or in gastric juice. Secondary endogenous pneumonia was pneumonia that developed after the fourth day of mechanical ventilation. Exogenous pneumonia was diagnosed when the etiologic microorganism was not isolated in pharyngeal swabs or in gastric juice before the development of pneumonia. Community flora was defined as the isolation of normal buccal flora (Neisseria species, Streptococcus viridans, among others), Streptococcus pneumoniae, or Haemophilus influenzae. A catheter-related infection was diagnosed when inflammatory signs occurred in a catheterized blood vessel together with a temperature of 38.3 C or more, irrespective of the isolation of a potentially pathogenic microorganism in the culture of the removed catheter. Likewise, this diagnosis was considered if the fever improved within 12 hours after removing the catheter. A urinary tract infection was diagnosed after fresh-voided catheter urine containing five or more leukocytes per high-power light-microscopic field were identified and a potentially pathogenic microorganism was isolated in urine culture in concentrations of 105 CFU/mL or more. A wound infection was diagnosed if purulent secretions from wounds occurred with signs of inflammation and the isolation of a potentially pathogenic microorganism in concentrations of 105 CFU/mL or more from the purulent wound secretions. Septicemia was diagnosed if clinical signs of systemic infection occurred, such as fever, leukocytosis, increased percentage of band forms, and metabolic acidosis, combined with a positive blood culture. Multiple organ system failure was defined as three or more organ systems failing for more than 2 consecutive days. Infection-relat

Histopathologic and Microbiologic Aspects of Ventilator-associated Pneumonia

BackgroundThe relationship between microbiology and histology in patients with ventilator-associated pneumonia has been sparsely described.MethodsTwenty-five patients who died in the intensive care unit after their lungs had been mechanically ventilated for 72 h were studied. Twenty of the 25 died w

Value of intracellular bacteria detection in the diagnosis of ventilator associated pneumonia.

BACKGROUND: Markers of ventilator associated pneumonia are of interest for confirming the diagnosis and for guiding the initial management of this frequent complication of mechanical ventilation. The detection of intracellular organisms in the polymorphonuclear leucocytes (PMNLs) and/or macrophages of bronchoalveolar lavage (BAL) fluid has been suggested as a specific test for the early indication of an infectious pulmonary process. METHODS: The diagnostic value of detecting intracellular organisms in two types of BAL fluid--protected (P-BAL) and conventional (C-BAL)--in 25 patients who died in one unit was prospectively studied. Immediately after death both P-BAL and C-BAL were performed bilaterally. Through a minithoracotomy on both sides of the chest bilateral bronchoscopically guided open lung biopsy samples were obtained from the same area, and an average of eight open lung blind biopsy samples (not bronchoscopically guided) were taken from each lung for histological examination. BAL fluid was examined for quantitative cultures (threshold 10(4) cfu/ml) and for the presence of intracellular organisms and extracellular organisms, and differential cell counts were also performed. RESULTS: Using the histopathology of the bronchoscopically guided open lung biopsies as the gold standard, detection of intracellular organisms in P-BAL (> or = 5%) and C-BAL (> or = 5%) fluids yielded 75% and 57% positive predictive values, and 83% negative predictive values, respectively. Prior treatment with antibiotics decreased the positive and negative predictive values of intracellular organism detection for both types of BAL fluid. The presence of intracellular organisms was correlated with the quantitative cultures of P-BAL and C-BAL samples. Quantitative cultures from P-BAL fluid were less sensitive (22% versus 45%) and more specific (100% versus 55%) than those from C-BAL samples. The percentage of extracellular organisms and the differential cell count in P-BAL and C-BAL samples could not discriminate between the presence or absence of pneumonia. CONCLUSIONS: The presence of > or = 5% intracellular organisms infecting PMNLs or macrophages in P-BAL or C-BAL fluids is a specific marker of ventilator associated pneumonia.

Respiratory infectious complications in the intensive care unit.

Ventilator-associated pneumonia is the most common infectious respiratory complication in intensive care unit patients, particularly those needing mechanical ventilation. Ventilator-associated pneumonia represents a challenging problem in terms of diagnosis, treatment, and prevention. Nosocomial sinusitis is another respiratory infection, not uncommon in mechanically ventilated patients. This type of infection has to be suspected in nasally intubated patients and may be a hidden focus of fever and sepsis.

Evaluation of antimicrobial treatment in mechanically ventilated patients with severe chronic obstructive pulmonary disease exacerbations.

Objective: To study microbial and susceptibility patterns and antimicrobial treatment responses in patients with severe, acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation. Design: Microbial investigation using tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage, as well as paired serologies. Evaluation of antimicrobial treatment by results of the initial investigation, susceptibility testing, and a repeated microbial investigation (tracheobronchial aspirates, bronchoscopy with a protected specimen brush, and bronchoalveolar lavage) after 72 hrs. Setting: A respiratory intensive care unit of a 1,000‐bed teaching hospital. Patients: Fifty severely exacerbated and mechanically ventilated patients with chronic obstructive pulmonary disease. Interventions: Initial empirical antimicrobial treatment according to clinical judgment. Measurements and Main Results: Overall, 36 of 50 patients (72%) had evidence of a microbial origin. Community‐acquired endogenous pathogens were present in 70% of patients, and Gram‐negative enteric bacilli and Pseudomonas/Stenotrophomonas species were present in 30%. All five isolates of Streptococcus pneumoniae were resistant to penicillin (three intermediately and two highly), and three were resistant to multiple antibiotics. Pseudomonas species revealed multiresistance in four of nine isolates (44%), and Stenotrophomonas maltophilia revealed multiresistance in one of two isolates. Antimicrobial treatment was modified according to diagnostic results in 11 of 31 patients (36%) with potentially pathogenic microorganisms. In patients who underwent a repeat investigation after 72 hrs, 24% of the initially present and potentially pathogenic microorganisms persisted. Inappropriate initial antimicrobial therapy was associated significantly with bacterial persistence (p < .002). Conclusions: Considering the diversity of microbial pathogens and the resistance rates especially to S. pneumoniae in this patient population, antimicrobial treatment should be based on the constant study of local microbial and susceptibility patterns along with routine microbial investigation of the individual patient.

INVASIVE DIAGNOSTIC TECHNIQUES FOR PNEUMONIA: PROTECTED SPECIMEN BRUSH, BRONCHOALVEOLAR LAVAGE, AND LUNG BIOPSY METHODS

We suggest the following strategy for managing patients with pneumonia. For nonventilated patients with either CAP or HAP, empiric antibiotic treatment should be started according to approved guidelines, and if the clinical evolution of the patient is not adequate, fiberoptic bronchoscopy including PSB and BAL could be considered, with modification of the antibiotic treatment accordingly. In ventilated patients with either CAP or HAP, respiratory secretion sampling using noninvasive techniques should be conducted upon clinical suspicion of VAP and before starting a new antibiotic treatment. Antibiotic therapy according to approved guidelines should be started as soon as possible and maintained during the first 48 hours if the patients evolution is satisfactory and condition has stabilized. Then, initial antibiotic treatment should be adjusted according to cultures. If there is a clear diagnostic alternative to VAP and cultures are negative, this is the only case in which antibiotic treatment could be withdrawn. If the patients clinical evolution is inadequate (persistence of fever, leukocytosis, increasing infiltrates, and respiratory failure), fiberoptic bronchoscopy with PSB and BAL and modification of the initial antibiotic regimen should be sought. Open lung biopsy may be indicated in patients with diffuse pulmonary infiltrates in whom a diagnosis has not been achieved by other methods, including bronchoscopy. Transbronchial lung biopsy should not be viewed as a diagnostic technique for pneumonia except in immunosuppressed patients with diffuse alveolar infiltrates.