Intrapulmonary neutrophil apoptosis in a pig model of pneumonia.

BACKGROUND: Apoptosis and necrosis are two distinct cell death modalities. Polymorphonuclear leukocytes (PMNL) play an important role in pneumonia and little information is available on whether these cells are cleared by necrosis or apoptosis. We therefore compared the proportion of apoptotic PMNL in lung tissues with and without pneumonia. In addition, the association of PMNL apoptosis and mechanical ventilation (MV) was investigated. METHODS: Samples obtained from a pig model developed to tracheobronchial stenting were analysed. Pneumonia was induced with that model in 10 animals (white-Landrace piglets, Pittman-Moore or Göttingen minipigs). Animals were sacrificed when clinical parameters of pneumonia became evident and 17 lung samples could be analysed for histologic evidence of pneumonia, growth of micro-organisms, and the apoptotic index (proportion of apoptotic PMNL over all PMNL in a 400-power field). In addition, lung samples (n = 7) from two pigs without stent implantation on mechanically ventilated for more than 48 h were studied. RESULTS: A total of 9/17 samples (53%) showed histologic evidence of pneumonia, 11/17 (65%) had significant bacterial growth (> 10(3) cfu/g), and 7/17 (41%) fulfilled both criteria. The apoptotic index was not significantly different in samples with and without histologic evidence of pneumonia (pneumonia: 25.3 +/- 6.1% vs. No pneumonia: 25.2 +/- 11.9%; 95%CI: -9.7 - 9.5, p = 0.989) or in samples with and without significant bacterial growth (significant bacterial growth: 23.5+/-9.3% vs. No significant bacterial growth: 28.5+/-8.2%; 95%CI: -4.6 - 16.7; p = 0.284). However, the apoptotic index was higher in samples of pigs, mechanically ventilated for more than 48 h, compared to the stent group (MV: 36.9+/-10.7% vs. Stent: 25.2 +/- 9.0%; 95% CI: -20.5 - -2.9; p = 0.012). CONCLUSION: In an animal model, the proportion of apoptotic PMNL was not different in lung samples with and without histologic or bacterial pneumonia. However, MV for more than 48 h was associated with a higher proportion of apoptotic PMNL in lung tissue. This study may be helpful for the understanding of the evolution of lung tissue damage induced by bacterial pneumonia and MV.

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.

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.

Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: a pilot study.

The aim of the study was to assess the potential role of glucocorticoids (GC) in modulating systemic and pulmonary inflammatory responses in mechanically ventilated patients with severe pneumonia. Twenty mechanically ventilated patients with pneumonia treated at a respiratory intensive care unit (RICU) of a 1,000-bed teaching hospital were prospectively studied. All patients had received prior antimicrobial treatment. Eleven patients received GC (mean+/-SD dose of i.v. methylprednisolone 677+/-508 mg for 9+/-7 days), mainly for bronchial dilatation. Serum and bronchoalveolar lavage fluid (BALF) tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and C-reactive protein levels were measured in all patients. The inflammatory response was attenuated in patients receiving GC, both systemically (IL-6 1,089+/-342 versus 630+/-385 pg x mL(-1), p=0.03; C-reactive protein 34+/-5 versus 19+/-5 mg x L(-1), p=0.04) and locally in BALF (TNF-alpha 118+/-50 versus 24+/-5 pg x mL(-1), p= 0.05; neutrophil count: 2.4+/-1.1 x 10(9) cells x L(-1) (93+/-3%) versus 1.9+/-1.8 x 10(9) cells x L(-1) (57+/-16%), p=0.03). Four of the 11 (36%) patients receiving GC died compared to six (67%) who were not receiving GC (p=0.37). The present pilot study suggests that glucocorticoids decrease systemic and lung inflammatory responses in mechanically ventilated patients with severe pneumonia receiving antimicrobial treatment.

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.

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.

Community-acquired pneumonia in the elderly.

The incidence of community-acquired pneumonia (CAP) in the elderly is higher compared to younger populations. In addition, pneumonia in the elderly is a life-threatening problem. As our demographics have changed, clinicians have developed a heightened interest in managing pneumonia in the elderly. The development of pneumonia in elderly patients differs from that in younger individuals due to a complex array of factors. (1) The organisms involved depend on the setting in which the pneumonia developed: either the nonhospitalized elderly patient with CAP or the institutionalized patient who develops nursing-home-acquired pneumonia. (2) Underlying comorbid conditions commonly exist in the elderly that affect the etiology and outcome of pneumonia. Overall, Streptococcus pneumoniae and Haemophilus influenzae are still the most common etiologies of pneumonia in the elderly. The true role of gram-negative bacilli remains unclear although these micro-organisms may be more common etiologic agents in nursing-home pneumonia. Some recent studies from Mediterranean areas have reported high rates of infection by Chlamydia pneumoniae, but the real role of this micro-organism has to be confirmed. Another important issue is that the presenting symptoms of pneumonia in the elderly can be subtle and sometimes difficult to recognize. Fever is frequently absent, and delirium or alteration of functional physical capacity may be the only manifestations. Mortality in the elderly with CAP is higher when compared to younger populations. However, this may be explained by the concomitant presence of comorbid conditions more than by age per se. This statement has to be kept in mind when considering hospital and, particularly, intensive care unit admissions. Finally, antibiotic pharmacokinetics in the elderly populations with CAP ought to be considered to avoid frequent side-effects and complications. Overall, antibiotic regimens in hospitalized elderly patients with CAP do not differ from other hospitalized CAP populations. An organized approach to assessing elderly patients with suspicion of pneumonia and an awareness of common pitfalls in the management of this pulmonary infection in this population are essential to improving outcomes.

Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury. Incidence, risk factors, and association with ventilator-associated pneumonia.

We prospectively evaluated the relation of upper airway, lower airway, and gastric colonization patterns with the development of pneumonia and its etiology in 48 patients with surgical (n = 25) and medical (n = 23) head injury. Initial colonization was assessed by cultures of nasal and pharyngeal swabs, tracheobronchial aspirates, gastric juice, and bronchoscopically retrieved protected specimen brush. Follow-up colonization was determined until the end points extubation, suspected ventilator-associated pneumonia (VAP), or death. The initial colonization rate at any site at ICU admission was 39/47 (83%). It mainly accounted for Group I pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae) of the upper and lower airways. At follow-up, colonization rates with Group II pathogens (Gram-negative enteric bacilli and Pseudomonas spp.) increased significantly. The high initial bacterial load with Group I pathogens of the upper airways and trachea decreased during Days 2 to 4, whereas that of Group II pathogens increased. Upper airway colonization was an independent predictor of follow-up tracheobronchial colonization (odds ratio [OR], 9.9; 95% confidence interval [CI], 1.8 to 56.3 for initial colonization with Group I pathogens; OR, 23.9; 95% CI, 3.8 to 153.3 for follow-up colonization with Group II pathogens). Previous (short-term) antibiotics had a protective effect against colonization with Group I pathogens of the lower respiratory tract (OR, 0.2; 95% CI, 0.05 to 0.86), but they were a risk factor for colonization with Group II pathogens (OR, 6.1; 95% CI, 1.3 to 29). Initial tracheobronchial colonization with Group I pathogens was associated with a higher probability of early onset pneumonia (OR, 4. 1; 95% CI, 0.7 to 23.3), whereas prolonged antibiotic treatment (> 24 h) independently predicted late-onset pneumonia (OR, 9.2; 95% CI, 1.7 to 51.3). We conclude that patients with head injury are colonized in the airways mainly by Group I pathogens early in the evolution of illness. The upper airways represent the main reservoir for subsequent lower airway colonization with Group I pathogens. Previous (short-term) antibiotic treatment is protective against initial tracheobronchial colonization with Group I pathogens, but it represents a risk factor for subsequent lower airway colonization by Group II pathogens.

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 patient's 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 patient's 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.

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.

Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation.

We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance. Quantitative cultures of tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and after 72 h, as well as serology for bacteria and respiratory viruses were performed. Fifty patients (mean age 68 +/- 8, 46 males) were studied prospectively. Potentially pathogenic microorganisms (PPMs) and/or a positive serology were present in 36 of 50 (72%) patients, including 12 (33%) polymicrobial cases. Only six (12%) had no pathogen in any sample in the absence of antimicrobial pretreatment. Microbial patterns corresponded to community-acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in 19 of 34 (56%) and to gram-negative enteric bacilli (GNEB), Pseudomonas, and Stenotrophomonas spp. in 15 of 34 (44%) of isolates. Chlamydia pneumoniae and respiratory viruses were found in 18% and 16% of investigations, respectively. Repeated investigation after 72 h in 19 patients with PPMs in the initial investigation revealed eradication of virtually all isolates of community-acquired pathogens and GNEB but persistence of three of five Pseudomonas spp. and both Stenotrophomonas spp. as well as the emergence of new GNEB, Pseudomonas and Stenotrophomonas spp. Clinical parameters neither predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp. Nevertheless, severe pneumonia attributable to initially isolated pathogens occurred in two patients with severe COPD exacerbation. We conclude that pathogens were more frequently present than previously reported. The rate of GNEB and Pseudomonas/Stenotrophomonas spp. isolates was high. The presence of pathogens was clinically unpredictable. Thus, in this population of patients with severe exacerbations of COPD, it may be advisable to obtain respiratory samples and to treat according to diagnostic results. Further studies are warranted to clarify this issue.

Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care.

The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to be acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.

Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia: a pilot study.

We performed an open, prospective, randomized clinical trial in 51 patients receiving mechanical ventilation for more than 72 h, in order to evaluate the impact of using either invasive (protected specimen brush [PSB] and bronchoalveolar lavage [BAL] via fiberoptic bronchoscopy) or noninvasive (quantitative endotracheal aspirates [QEA]) diagnostic methods on the morbidity and mortality of ventilator-associated pneumonia (VAP). Patients were randomly assigned to two groups: Group A patients (n = 24) underwent QEA, PSB, and BAL; Group B patients (n = 27) underwent only QEA cultures. Empiric antibiotic treatment was given according to the attending physician and was modified according to the results of cultures and sensitivity in Group A using PSB and BAL results and in Group B based upon QEA cultures. Bacteriologic cultures were done quantitatively for EA, PSB, and BAL. Thresholds of > or = 10(5), > or = 10(3), and > or = 10(4) CFU/ml were used for QEA, PSB, and BAL, respectively. Microbial cultures from Group A patients were positive in 16 (67%) BAL samples, 14 (58%) PSB samples, and 16 (67%) QEA samples. In Group B patients, QEA microbial cultures yielded positive results in 20 of 27 (74%) samples. In Group A, there was total agreement between culture results of the three techniques on 17 (71%) occasions. In five (21%) cases, QEA coincided with either BAL or PBS. In only two (8%) cases, QEA cultures did not coincide with either PSB or BAL. No cases of positive BAL or PSB cultures had negative QEA cultures. Initial antibiotic treatment was modified in 10 (42%) patients from Group A and in four (16%) patients from Group B (p < 0.05). The observed crude mortality rate was 11 of 24 (46%) in Group A, and 7 of 27 (26%) in Group B, whereas the adjusted mortality rates (observed crude minus predicted at admission) for Groups A and B were 29 and 10%, respectively. There were no statistically significant differences when comparing crude and adjusted mortality rates of Groups A and B. There were no differences in mortality between both groups when comparing pneumonia, considering together Pseudomonas aeruginosa and Acinetobacter spp. (Group A, 33% versus Group B, 27%). There were no differences between Groups A and B with regard to ICU stay duration and total duration of mechanical ventilation. In this pilot study, the impact of bronchoscopy was to lead to more frequent antibiotic changes with no change in mortality. Further studies with larger population samples are warranted to confirm these findings.

Community-acquired pneumonia in the elderly. Clinical and nutritional aspects.

Community-acquired pneumonia (CAP) in the elderly has a different clinical presentation than CAP in other age groups. Confusion, alteration of functional physical capacity, and decompensation of underlying illnesses may appear as unique manifestations. Malnutrition is also an associated feature of CAP in this population. We undertook a study to assess the clinical and nutritional aspects of CAP requiring hospitalization in elderly patients (over 65 yr of age). One hundred and one patients with pneumonia, consecutively admitted to a 1,000-bed teaching hospital over an 8-mo period, were studied (age: 78 +/- 8 yr, mean +/- SD). Nutritional aspects and the mental status of patients with pneumonia were compared with those of a control population (n = 101) matched for gender, age, and date of hospitalization. The main symptoms were dyspnea (n = 71), cough (n = 67), and fever (n = 64). The association of these symptoms with CAP was observed in only 32 patients. The most common associated conditions were cardiac disease (n = 38) and chronic obstructive pulmonary disease (COPD) (n = 30). Seventy-seven (76%) episodes of pneumonia were clinically classified as typical and 24 as atypical. There was no association between the type of isolated microorganism and the clinical presentation of CAP, except for pleuritic chest pain, which was more common in pneumonia episodes caused by classical microorganisms (p = 0.02). This was confirmed by a multivariate analysis (relative risk [RR] = 11; 95% confidence interval [CI]: 1.7 to 65; p = 0.0099). The prevalence of chronic dementia was similar in the pneumonia cohort (n = 25) and control group (n = 18) (p = 0.22). However, delirium or acute confusion were significantly more frequent in the pneumonia cohort than in controls (45 versus 29 episodes; p = 0.019). Only 16 patients with pneumonia were considered to be well nourished, as compared with 47 control patients (p = 0.001). Kwashiorkor-like malnutrition was the predominant type of malnutrition (n = 65; 70%) in the pneumonia patients as compared with the control patients (n = 31; 31%) (p = 0.001). The observed mortality was 26% (n = 26). Pleuritic chest pain is the only clinical symptom that can guide an empiric therapeutic strategy in CAP (typical versus atypical pneumonia). Both delirium and malnutrition were very common clinical manifestations of CAP in our study population.

Prognostic factors of severe Legionella pneumonia requiring admission to ICU.

Despite the fact that the epidemiology of community-acquired pneumonia and nosocomial Legionella infection is well known, there are no specific reports dealing with severe cases of Legionella pneumophila pneumonia admitted to intensive care units. We undertook a prospective study upon 84 patients with a reliable diagnosis of L. pneumophila pneumonia that required ICU admission. The study assessed the prognostic factors, clinical, radiological and outcome variables of both nosocomial (n = 33) and community-acquired (n = 51) cases of L. pneumophila pneumonia. The following variables were more common in nosocomial acquired as compared to community-acquired Legionella pneumonia: Chronic obstructive pulmonary disease (COPD) (64 versus 41%), cardiac disease (39 versus 10%), chronic renal failure (21 versus 4%), alcoholism (54 versus 18%), septic shock (33 versus 16%), and unilateral chest X-ray involvement (61 versus 39%). The crude mortality rate in this study was 30% (25 of 84) with no differences when comparing mortality between nosocomial (9, 27%) to community-acquired (16, 31%) types. The univariate analysis showed that cardiac disease, diabetes mellitus, creatinine > or = 1.8 mg/dl, septic shock, chest X-ray extension, mechanical ventilation, hyponatremia < or = 136 mEq/L, PACO2/FIO2 < 130, and blood urea levels > or = 30 mg/dl were factors related to poor outcome. On the other hand, the following two variables were related to better outcome: adequate treatment for Legionella and pneumonia improvement. The logistic regression analysis demonstrated that APACHE II score > 15 at admission (RR: 11.5; 95% CI 1.75 to 76.1; p = 0.025), and serum Na levels < or = 136 (RR: 21.3; 95% CI 1.11 to 408; p = 0.023), were the only independent factors related to death. On the other hand, improving pneumonia is associated with better outcome in Legionnaires' disease than for patients not having improving pneumonia (RR: 0.019; 95% CI: 0.036 to 0.106; p < 0.0001). A better understanding of the prognostic factors in cases of severe Legionella pneumonia will optimize our therapeutic approach in this disease and help to decrease both its mortality and morbidity rates.

Significance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients. An immediate postmortem histologic study.

The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study on 25 non-neutropenic, mechanically ventilated (> 72 h) patients who died in our ICU with the aim of assessing the incidence and significance of the isolation of Candida species from quantitative cultures of immediate postmortem lung biopsies and different respiratory sampling techniques. Immediate postmortem respiratory samples (endotracheal aspirate, protected specimen brush [PSB], bronchoalveolar lavage [BAL], blind biopsies [average 14/patient], and bilateral bronchoscopically guided biopsies [two per patient]) were taken from all patients. Lung tissue specimens were histologically examined. Respiratory samples were classified as having Candida or otherwise. Ten (40%) patients had at least one pulmonary biopsy yielding Candida spp. Among these 10 patients with Candida isolates, only two had definite pulmonary candidiasis. A total of 470 microorganisms were isolated from 280 of 375 (77%) lung biopsy samples in all 25 patients. Candida species represented 9% (n = 40) of the isolates, corresponding to 10 patients (40%). In the 10 patients in whom Candida species was isolated from pulmonary biopsies, this was always associated with the isolation of the same microorganism from one of the sampling methods. Quantitative cultures of Candida species from different sampling methods correlated well among each other but could not discriminate the presence from absence of Candida pneumonia. A logistic regression model adjusted for the presence of antibiotics, days of antibiotic treatment, mechanical ventilation period, age, ARDS, parenteral nutrition, and gender did not show any independent risk factor for developing positive pulmonary samples for Candida species. The incidence of Candida isolation from pulmonary biopsies in critically ill mechanically ventilated, non-neutropenic patients who die is high (40%). However, the incidence of definite Candida pneumonia was 8%. We also found that Candida colonization is uniform throughout the different lung regions, and that the presence of Candida in respiratory samples, independently of quantitative cultures, is not a good marker of Candida pneumonia in critically ill, non-neutropenic, non-AIDS patients.

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.

Protective effect of intravenously administered cefuroxime against nosocomial pneumonia in patients with structural coma.

In comatose patients admitted to an ICU, particularly those with head injury, the incidence of early onset pneumonia is exceedingly high. We performed an open, prospective, randomized, and controlled clinical trial aiming at the reduction of the incidence of ventilator-associated pneumonia in head-injured patients and patients with stroke requiring mechanical ventilation. One hundred patients were included because of head injury or coma caused by medical stroke and with Glasgow coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for the study (n = 50) received cefuroxime intravenously (two 1,500-mg doses 12 h apart after intubation) (the cefuroxime group) and 50 patients not receiving cefuroxime formed the control group. In the former group patients did not receive any other antibiotics before the end-point determination, whereas in the latter, 17 patients received prophylactic antibiotics as prescribed by the attending physician. The global incidence of microbiologically confirmed pneumonia was 37% (n = 37); 12 (24%) belonged to the cefuroxime group, and 25 (50%) belonged to the control group (p = 0.007). Early-onset pneumonia accounted for 70% of all the pneumonia episodes (n = 26), eight (67%) belonging to the cefuroxime group, and 18 (72%) belonging to the control group (p = 0.02). In the control group, four of 17 (23%) patients receiving prior antibiotics developed pneumonia, whereas 21 of 33 (64%) patients who did not receive antibiotics developed pneumonia (p = 0.016). The multivariate analysis revealed that the duration of mechanical ventilation (per each day) was an independent risk factor significantly associated to the development of pneumonia. Furthermore, the use of cefuroxime and/or prior antibiotics in the control group, before the pneumonia episode, had a protective effect against its development. No differences were found with regard to mortality and morbidity when comparing the study population with the control group. Nevertheless, when comparing patients with pneumonia (from both study and control groups) with those without it, there was a decrease in total hospital stay (35 +/- 13 versus 25 +/- 14 d, p = 0.048) and ICU stay (20 +/- 11 versus 11 +/- 7 d, p = 0.001). The study demonstrated that the administration of two single high doses 1,500 mg each of cefuroxime after the intubation of patients comatose because of head injury or medical stroke is an effective prophylactic strategy to decrease the incidence of ventilator-associated pneumonia.