[Nosocomial pneumonia: prevention, diagnosis, treatment].
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Biomedical subjects
Publications and source records attributed to S Ewig.
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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.
Streptococcus pneumoniae is still the most important pathogen of community-acquired respiratory tract infections. During the last decades in many countries an increase in the spread of antibiotic resistant strains (e. g. against beta-lactams, macrolides, tetracyclin) was observed. Resistance against penicillin is often associated with resistance against macrolides and other antibiotic classes. In Germany surveillance studies including isolates from patients with community-acquired respiratory tract infections have shown that about 14 % of strains show a reduced susceptibility against penicillin (MIC-values 0.12 - 1 mg/L) and up to 4 % are highly resistant against penicillin (MIC >/= 2 mg/L). Resistance against tetracycline or macrolides was detected in up to 12 and 15 % of strains, respectively. According to the treatment guidelines of the Paul-Ehrlich-Gesellschaft für Chemotherapie and the Deutschen Atemwegsliga penicillins and cephalosporins are recommended as first line antibiotics for the treatment of community-acquired respiratory tract infections. As pneumococcal strains with reduced susceptibility against penicillin show often also a reduced susceptibility against cephalosporins the questions arises which beta-lactam antibiotics should still be used in empirical treatment of such strains. beta-Lactam-antibiotics highly differ in their in-vitro-activity against S. pneumoniae and their pharmacokinetic properties. In different models is has been demonstrated for beta-lactams that an adequate clinical and bacteriological efficacy is achievable when the serum levels of the free, i. e. not protein bound fraction of drug exceeds the MIC of the pathogen for at least 40 to 50 % of the dosing interval (T > MIC). In a clinical situation where pneumococci with reduced susceptibility against penicillin cannot be ruled out, only beta-lactam antibiotics with favourable pharmacological properties (good in-vitro activity, high and long lasting serum levels) should be used for treatment.
Legionellosis is a relatively rare condition but nevertheless is associated more frequently than many other pathogens with a severe course. Therefore, establishing a diagnosis of Legionellosis remains a challenge. The most significant progress in the diagnosis of Legionellosis is antigen-testing in urine by a rapid immunochromatographic test (ICT). This is an easy to handle bedside test which provides a result within 15 minutes. Sensitivity and specificity reach 80 % and 100 %, respectively. However, the exact place of this test within algorithms of clinical decision making still remains unsettled. Macrolides, doxycycline, fluoroquinolones and ketolides, and possibly also streptogramins are drugs with definitely or most probably sufficient activity against Legionella spp. and, therefore, are appropriate candidates within empirical initial antimicrobial treatment regimen of community-acquired pneumonia. Macrolides and fluoroquinolones should be the drugs of choice for the treatment of established Legionellosis. Oral macrolides should be prefered in patients with mild to moderate pneumonia; within the macrolides, azithromycin has the most favourable profile of activity. Alternatively, ciprofloxacin, levofloxacin and moxifloxacin may be selected. In severe Legionellosis as well as independently of severity in nosocomial legionellosis and immunosuppressed patients, intravenous fluoroquinolones are first choice drugs. Alternatively, azithromycin may be used. Whether a combination treatment including azithromycin or fluoroquinolones with rifampin or azithromycin with fluoroquinolone exert superior activity remains currently unknown.
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A case-control-study was performed to identify patients at particularly high risk of community-acquired pneumonia and nosocomial pneumonia with a special focus on cardiovascular diseases as potential risk factors. Thirty-six consecutive hospitalized patients with cardiovascular diseases and pneumonia were matched with 36 controls also suffering from cardiovascular diseases but without pneumonia. From all cardiovascular diseases only heart failure proved to be an independent risk factor for pneumonia (OR 5.69, 95 % KI 1.69 - 19.04, p = 0.0048). Both chronic (p = 0.009) and acute heart failure (p = 0.028) were associated with an increased risk of pneumonia. The risk of pneumonia was closely related to the degree of ventricular function impairment. Coronary heart disease, valvular disease, arrythmia, myocarditis, endocarditis and cardiomyopathy did not increase the risk for pneumonia unless accompanied by heart failure. Pulmonary (OR 9.24, 95 % KI 1.48 - 57.74, p = 0.00174) and renal diseases (OR 7.49, 95 % KI 1.38 - 40.76, p = 0.0197) were validated as additional independent risk factors. A history of smoking was also associated with an increased risk of pneumonia (p = 0,023). This study supports the hypothesis that heart failure resulting from cardiovascular disease and not cardiovascular disease itself mounts the risk for pneumonia.
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Much progress has been made in the understanding of nosocomial pneumonia but important issues in diagnosis and treatment remain unresolved. The controversy over diagnostic tools should be closed. Instead, every effort should be made to increase our ability to make valid clinical predictions about the presence of ventilator associated pneumonia and to establish criteria to guide restricting empirical antimicrobial treatment without causing patient harm. More emphasis must be put on local infection control measures such as routine surveillance of pathogens, definition of controlled policies of antimicrobial treatment, and effective implementation of strategies of prevention.
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Despite comprehensive diagnostic work-up, the aetiology of community-acquired pneumonia (CAP) remains undetermined in 30-60% of cases. The authors studied factors associated with undiagnosed pneumonia. Patients hospitalised with CAP and being evaluated by two blood cultures, at least one valid lower respiratory tract sample, and serology on admission were prospectively recorded. Patients who had received antimicrobial pretreatment were excluded. Patients with definite or probable aetiology were compared to those with undetermined aetiology by uni- and multivariable analysis. A total 204 patients were eligible for the study. The aetiology remained undetermined in 82 (40%) patients, whereas a definite aetiology could be established in 89 (44%) and a probable one in 33 (16%). In multivariable analysis, factors associated with undetermined aetiology included age >70 yrs, renal and cardiac comorbidity, and nonalveolar infiltrates on the chest radiograph. There was no association of undiagnosed pneumonia with mortality. Age and host factors were associated with unknown aetiology of community-acquired pneumonia. Some of these cases may also represent fluid volume overload mimicking pneumonia.
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OBJECTIVE: To assess the effect of bronchoalveolar lavage (BAL) volume on arterial oxygenation in critically ill patients with pneumonia. DESIGN: Randomized clinical comparison. SETTING: Six-bed respiratory intensive care unit of a 850-bed tertiary care university hospital. PATIENTS: Thirty-seven intubated and mechanically ventilated patients with clinical suspicion of pneumonia. INTERVENTIONS: Bronchoscopically guided protected specimen brush (PSB) followed by either a "high volume" BAL (n = 16, protected catheter, mean volume: 131 +/- 14 ml) or a "low volume" BAL (n = 21, protected double-plugged catheter, 40 ml volume for all patients). MEASUREMENTS: Arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2) and mean arterial pressure (MAP) before and up to 24 h after the intervention. Bacterial growth in quantitative cultures. Analysis of variance for repeated measurements with inter-subject factors. RESULTS: All patients showed a lower PaO2/FIO2 ratio and higher MAP after the diagnostic procedure, without differences between the study arms (p = 0.608 and p = 0.967, respectively). Patients with significant bacterial growth (p = 0.014) and patients without preemptive antibiotic (p = 0.042) therapy showed a more profound and longer decrease in arterial oxygenation after the diagnostic procedure. CONCLUSIONS: A decrease in the PaO2/FIO2 ratio was observed in all patients after a combined diagnostic procedure, independent of the BAL volume used. A significant bacterial burden recovered from the alveoli and no preemptive antibiotic therapy were associated with a larger and longer-lasting decrease in arterial oxygenation.
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Patients hospitalized with community-acquired pneumonia caused by S. pneumoniae strains with intermediate susceptibility to penicillin according to the conventional definition respond well to treatment with adequate doses of beta-lactam antibiotics. All studies currently available comparing mortality between patients with pneumonia caused by nonsusceptible and susceptible pneumococci agree that resistance of MIC 2 mg/L is not associated independently with an increased mortality. Most but not all studies could not prove an effect of microbial resistance on morbidity. There are data suggesting, however, that pneumococcal pneumonia caused by highly resistant strains (MIC > or = 4 mg/L) does affect the outcome. Pneumococcal resistance remains a matter of concern. Most reports show an increase not only of resistance rates, but also of the proportion of highly resistant strains. The selection of initial empirical antimicrobial treatment of patients with community-acquired pneumonia should be performed judiciously. Because the serum and pulmonary levels achieved with penicillin or related drugs are several times higher than the MICs of most strains, pneumonias caused by S. pneumoniae currently defined as not susceptible to penicillin should respond well to treatment with a beta-lactam antibiotic, used in optimal doses. Consequently, there is no reason fundamentally to change the current approach to initial empiric antimicrobial treatment of patients with community-acquired pneumonia. Nevertheless, increases in resistance to macrolides may prompt a limited use of these drugs in the outpatient setting. In any case, treatment failures may occur at higher levels of resistance, and a change in the definition of susceptibility categories toward higher cutoffs for S. pneumoniae seems to be reasonable.