Moxifloxacin: update and perspectives after 8 years of usage.

Moxifloxacin has a broad spectrum of activity, including Gram-positive and Gram-negative organisms, atypical respiratory pathogens, anaerobes and penicillin- and macrolide-resistant Streptococcus pneumoniae. It achieves good tissue penetration and high concentrations in clinically relevant tissues and fluids. It is available in both an oral and intravenous formulation, has a once-daily administration and a good tolerance and safety profile. Moxifloxacin is used mainly for the treatment of acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, acute bacterial sinusitis, complicated skin and skin-structure infections and complicated intra-abdominal infections, as well as pulmonary TB, although it is not approved in this indication. The most recent studies covering these clinical indications are discussed.

Treatment of pneumonia in elderly patients.

Pneumonia represents the leading cause of infection-related death and the fifth cause of overall mortality, in the elderly. Several risk factors for acquiring pneumonia in older age have been reported, such as alcoholism, lung and heart diseases, nursing home residence and swallowing disorders. The clinical characteristics of pneumonia in the elderly differ substantially compared with younger patients, and the severity of the disease is strongly associated with increased age and age-related comorbidities. Streptococcus pneumoniae is the leading pathogen responsible for pneumonia in elderly; enteric Gram-negative rods should be considered in nursing-home-acquired pneumonia, as well anaerobes in patients with aspiration pneumonia. Antimicrobial therapy should take into account the most recent guidelines, which are briefly presented in this review. A special consideration should be given to the preventive measures, including vaccination, oral care and nutrition.

Apoptosis of peripheral blood neutrophils in COPD exacerbation does not correlate with serum cytokines.

The study investigated the relationship between apoptosis of peripheral blood neutrophils during exacerbation of chronic obstructive pulmonary disease (COPD) and the inflammatory response that characterises this condition. Twenty-six hospitalised patients with COPD exacerbation and 13 controls were included. Three sequential blood and sputum samples were obtained from patients at admission, after 3 days and at discharge. Blood apoptotic neutrophils were measured by flow-cytometry and light microscopy. Serum and sputum levels of IL-6, IL-8 and TNF-alpha were determined by an immunoassay technique. We found a significantly reduced percentage of apoptotic neutrophils at the onset of COPD exacerbation which increased over time (1.1+/-0.4% at admission vs. 2.4+/-0.4% at discharge, P<0.0001). Patients presented no changes in serum cytokines neither during exacerbation nor in comparison to controls. In contrast, sputum levels of cytokines were significantly increased compared to serum levels. There was no significant correlation between the apoptotic neutrophils and the cytokine concentrations in serum or sputum. None of the clinical parameters, such as smoking, microbial infection, corticosteroids or hypoxemia showed a correlation with neutrophil apoptosis. No relationship could be found between the reduced percentage of apoptotic neutrophils in blood and serum concentration of IL-6, IL-8 and TNF-alpha or other clinical parameters in patients with COPD exacerbation.

Microbial airway colonization is associated with noninvasive ventilation failure in exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: Abnormal airway colonization in patients with chronic obstructive pulmonary disease (COPD) needing invasive mechanical ventilation (IMV) is considered a first step in the acquisition of nosocomial pneumonia. Noninvasive ventilation (NIV) could potentially avoid this, but airway colonization has not been studied in patients who undergo NIV. We hypothesized that patients undergoing NIV would have lower rates of colonization than patients undergoing IMV. The aim of the study was to assess the microbial airway colonization in patients with exacerbated COPD needing NIV and IMV. DESIGN: A 2-yr prospective cohort study. SETTING: Respiratory intensive and intermediate care unit. PATIENTS: Eighty-six patients with exacerbated COPD undergoing NIV on admission (64 successes and 22 failures, according to subsequent intubation), and 51 patients undergoing IMV on admission. INTERVENTIONS: Quantitative culture specimens of sputum or tracheal aspirate were collected on admission and at follow-up (day 3) during NIV or IMV, respectively. Clinical assessment, including severity scores, and arterial blood gas measurements were also determined. MEASUREMENTS AND MAIN RESULTS: Compared with the NIV-success group, colonization by potentially pathogenic microorganisms was greater in the NIV-failure group on admission (13 [59%] vs. 14 [22%]; p < .001) and at follow-up while patients still underwent NIV (14 [93%] vs. 7 [14%]; p < .001), and it was even higher than during IMV at follow-up (20 [50%]; p = .027). Colonization by nonfermenting Gram-negative bacilli, mainly Pseudomonas aeruginosa, was significantly associated with NIV failure on admission (OR, 5.6; p = .016) and at follow-up (OR, 23.5; p < .001). Moreover, colonization by these microorganisms at follow-up (OR, 8.8; p = .008) and inadequate antimicrobial treatment (OR 11.3; p = .001) were associated with increased hospital mortality. CONCLUSIONS: Airway colonization by nonfermenting Gram-negative bacilli is strongly associated with NIV failure. Because it occurs before intubation, this would be a marker rather than just a consequence of NIV failure necessitating intubation. The efficacy of decreasing airway colonization in preventing NIV failure needs to be assessed.

New antibiotics for the treatment of severe staphylococcal infection in the critically ill patient.

PURPOSE OF REVIEW: Infection by Staphylococcus aureus in critically ill patients is usually associated with antimicrobial resistance and high mortality. A more effective antibiotic treatment is needed to replace older drugs that have limited efficacy. Novel substances active on methicillin-resistant Staphylococcus aureus, which are already available on the market or are still in development, are discussed in this review, with emphasis on nosocomial infections. RECENT FINDINGS: A number of new antibiotics are on the market (linezolid, quinupristin-dalfopristin, daptomycin) and there is good evidence regarding their efficacy, especially in methicillin-resistant Staphylococcus aureus infections. Linezolid is, to date, the best alternative in treating nosocomial pneumonia by methicillin-resistant Staphylococcus aureus. It is cost-effective; resistance levels are still very low but there are some concerns regarding its adverse events. Quinupristin-dalfopristin shows good activity in vitro but its efficacy in patients with pneumonia by methicillin-resistant Staphylococcus aureus is modest. Daptomycin is not recommended for pulmonary infections because of its reduced penetration in the lung tissue. Under current phase III trials in patients with nosocomial infections are tigecycline, ceftobiprole, and three new glycopeptides, all with particular activity against methicillin-resistant Staphylococcus aureus. SUMMARY: For the moment, there are limited and rather expensive therapeutic options for the infections by Staphylococcus aureus in the critically ill. No dramatic superiority of the new drugs in comparison to the standard therapies was observed in most of the clinical trials. Better results on the efficacy of the drugs under investigation are expected.

Causes and predictors of nonresponse to treatment of intensive care unit-acquired pneumonia.

OBJECTIVE: To prospectively evaluate the predictive factors for the nonresponse to empirical antibiotic treatment and mortality in patients with intensive care unit-acquired pneumonia. DESIGN: A 1-yr prospective cohort of patients with suspicion of intensive care unit-acquired pneumonia. SETTING: Five medical and surgical intensive care units of Hospital Clinic in Barcelona. PATIENTS: A total of 71 patients with intensive care unit-acquired pneumonia were studied. The definition of nonresponse included at least one of the following: failure to improve the Pao2/Fio2 ratio or need of intubation because of pneumonia, persistence of fever or hypothermia and purulent respiratory secretions, worsening of pulmonary infiltrates, or occurrence of septic shock or multiple organ dysfunction not present at onset of pneumonia. INTERVENTIONS: Clinical assessment, including severity scores, blood and quantitative cultures of respiratory secretions, and cytokine measurements in serum and bronchoalveolar lavage at onset of pneumonia and 72 hrs after antimicrobial treatment. MEASUREMENTS AND RESULTS: A total of 44 patients (62%) fulfilled criteria of nonresponse, and at least one cause of nonresponse could be determined in 28 cases (64%): inappropriate treatment in ten (23%), superinfection in six (14%), concomitant foci of infection in 12 (27%), and noninfectious causes in seven cases (16%). The remaining 16 patients with no definite cause of nonresponse presented with septic shock, multiple organ dysfunction, or acute respiratory distress syndrome. Increased levels of interleukin-6 at onset of pneumonia (odds ratio, 9.7; p =.014) was an independent predictor of nonresponse to treatment. Likewise, increased level of interleukin-6 at follow-up (odds ratio, 27; p =.001) was the only independent predictor for hospital mortality. CONCLUSION: Increased systemic inflammatory response was the main predictor of nonresponse to treatment and mortality.

Treatment failures in patients with ventilator-associated pneumonia.

Treatment failures in patients with VAP are a complex issue and form a major challenge for clinicians. The following key elements inherent to a rational approach to treatment failures have been elucidated: (1) the presence of treatment failure must be thoroughly defined and assessed; (2) the many causes behind treatment failures must be realized, particularly the possibility of pneumonia-related and extrapulmonary reasons; (3) the recognition of different patterns of treatment failures as a useful framework for decisions about modalities and intensity of diagnostic reassessment; and (4) the establishment of a protocol for the search of pulmonary and extrapulmonary sites of infection and noninfectious causes of nonresponse. Only such a rational approach precludes the adverse effects of blind empiricism, which always implies a dangerous and costly overtreatment. Many issues related to treatment failures remain unsettled, and efforts will have to be made in the future to improve current clinical attitudes to treatment failures in VAP.

[Bronchoalveolar lavage findings in the pulmonary impairment related to systemic sclerosis]. / Evaluarea prin lavaj bronhiolo-alveolar a afectarii pulmonare din scleroza sistemica.

UNLABELLED: The main objective of the study was to evaluate the relationship between the findings of the bronchoalveolar lavage (BAL) and the lung function in patients with systemic sclerosis and subsequent pulmonary impairment. The study was retrospective and included 17 cases with systemic sclerosis and pulmonary involvement investigated at "Marius Nasta" Institute. Bucharest, between January 1999-August 2001. Lung function assessment found the following: VC (% of predicted) = 82.5 +/- 14; DLCO (% of predicted) = 67.5 +/- 23.2. Cell count in BAL fluid showed: total number of cells x 10(6) = 11.5 +/- 6; lymphocytes (%) = 22.9 +/- 15.4; neutrophils (%) = 15.2 +/- 13.4; eosinophils (%) = 1.9 +/- 0.9; macrophages (%) = 58.1 +/- 19.8. We also compared the cell pattern according to DLCO value: the patients with DLCO > 80% had increased levels of eosinophils (5.2 +/- 4.9 vs 0.9 +/- 0.2, p = 0.007) while the group with DLCO < 80% presented significantly higher levels of neutrophils (16.1 +/- 15.5 vs 12.6 +/- 2.8, p = 0.003) compared to the group with normal lung function. CONCLUSIONS: Patients with systemic sclerosis and normal lung function present an increased level of eosinophils in BAL fluid, suggesting a transitory alveolitis. In change, those with DLCO < 80% have a higher level of neutrophils, usually associated to pulmonary fibrosis. The investigation by BAL appears to be a reliable tool for the assessment of the pulmonary impairment related to systemic sclerosis.