Biomedical subjects

Antonio Anzueto

Publications and source records attributed to Antonio Anzueto.

At least 37 records · Page 2Linked to original sources

PubMed2005

The impact of prior outpatient ACE inhibitor use on 30-day mortality for patients hospitalized with community-acquired pneumonia.

BACKGROUND: Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22-0.89) was significantly associated with 30-day mortality. CONCLUSION: Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.

Adult↗

PubMed2005

The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia.

BACKGROUND: Recent studies suggest that HMG-CoA reductase inhibitors ("statins") may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of statins on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation. RESULTS: Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk based on the pneumonia severity index. In the multivariable regression analysis, after adjusting for potential confounders including a propensity score, the use of statins at presentation (odds ratio 0.36, 95% confidence interval 0.14-0.92) was associated with decreased 30-day mortality. DISCUSSION: Prior outpatient statin use was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.

Cohort Studies↗

PubMed2005

Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients.

OBJECTIVE: A single-center retrospective study initial recently identified ventilator settings as a major risk factor for the development of acute respiratory distress syndrome (ARDS) in mechanically ventilated patients who do not have ARDS from the outset. We tested this hypothesis in a larger sample of patients prospectively enrolled in a multicenter study on mechanical ventilation. DESIGN AND SETTING: From a large international mechanical ventilation study database we identified patients who required mechanical ventilation for 48 h or more but did not have ARDS at the onset of mechanical ventilation. We extracted information on demographics, initial severity of illness, ventilator settings and major underlying ARDS risk factors. Primary outcome was development of ARDS after the onset of mechanical ventilation. MEASUREMENTS AND RESULTS: Of 3,261 mechanically ventilated patients who did not have ARDS at the outset 205 (6.2%) developed ARDS 48 h or more after the onset of mechanical ventilation. Multivariate logistic regression analysis adjusted for baseline patient characteristics (age, gender, Simplified Acute Physiology Score, hypoxemia) and underlying ARDS risk factors (sepsis, trauma, pneumonia) found the development of ARDS to be associated with the initial ventilator settings: high tidal volume (odds ratio 2.6 for tidal volume>700 ml), high peak airway pressure (odds ratio 1.6 for peak airway pressure>30 cmH2O), and high positive end-expiratory pressure (odds ratio 1.7 for end-expiratory pressure>5 cmH2O). CONCLUSIONS: The association with the potentially injurious initial ventilator settings, in particular large tidal volumes, suggests that ARDS in mechanically ventilated patients is in part a preventable complication. This hypothesis needs to be tested in a prospective study.

Female↗

PubMed2005

Antibiotic activity of telithromycin and comparators against bacterial pathogens isolated from 3,043 patients with acute exacerbation of chronic bronchitis.

BACKGROUND: Antimicrobial therapy is considered an important component in the medical management of most patients with acute exacerbation of chronic bronchitis (AECB). The three predominant bacterial species isolated are nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Staphylococcus aureus is also frequently isolated while atypical bacteria are thought to cause up to 10% of exacerbations. Antibacterial resistance is increasing worldwide and little surveillance data exist concerning pathogens isolated from patients with AECB. METHODS: This study examines the prevalence of antibacterial resistance in isolates obtained from patients with clinically diagnosed AECB. A total of 3043 isolates were obtained from 85 centres in 29 countries, between 1999-2003, and were tested against the new ketolide telithromycin and a panel of commonly used antibiotics. RESULTS AND DISCUSSION: Of the S. pneumoniae isolates, 99.9% were susceptible to telithromycin, but only 71% were susceptible to erythromycin and 75.3% to penicillin. Of the H. influenzae isolates, 99.6% were susceptible to telithromycin. 11.7% of these isolates produced beta-lactamase. Almost 10% of S. pneumoniae were multidrug-resistant; 99.0% of these isolates were susceptible to telithromycin. Telithromycin also demonstrated good in vitro activity against M. catarrhalis (MIC90 = 0.12 mg/L) and was the most active compound against methicillin-susceptible S. aureus (98.9% susceptible). CONCLUSION: Telithromycin demonstrated similar or better activity against the bacterial species investigated than the other agents, with the most complete coverage overall. These species are the predominant causative bacterial pathogens in AECB and thus the spectrum of activity of telithromycin makes it a potential alternative for the empirical treatment of AECB.

Adult↗

PubMed2005

Appropriate outpatient treatment of acute bacterial exacerbations of chronic bronchitis.

Acute exacerbations of chronic bronchitis (AECB), which are characteristic of chronic obstructive pulmonary disease (COPD), contribute to morbidity and decreased quality of life for patients with COPD. A significant proportion of these exacerbations are due to bacterial infections. The Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria provide guidance for choosing the optimal drug at its optimal dose and duration for antimicrobial treatment of AECB due to bacterial infection. Evidence-based guidelines recommend stratifying patients according to risk factors to improve selection of targeted antimicrobial therapy. With increasing rates of resistance to some antimicrobials, resistance is also an important consideration for reducing treatment failures and decreasing the need for further pharmacologic treatment. Fluoroquinolones are recommended as first-line therapy for patients with chronic bronchitis who have risk factors; gatifloxacin, gemifloxacin, and levofloxacin are highly active against commonly encountered pathogens. Safety profiles are an important consideration because adverse events and poor tolerability can reduce patient adherence rates, which in turn can lead to poorer outcomes. Safety profiles also become an important consideration as shorter-course, higher-dose therapies become more prevalent. First-line therapy with a well-tolerated antibiotic that is active against the predominant pathogens, combined with low resistance rates and a convenient once-a-day dosing regimen, may reduce overall costs. Fluoroquinolones exhibit low resistance, good activity levels, and high respiratory penetration, and they are particularly well suited for shorter-course, higher-dose regimens in selected patients. Shorter-course, higher dose regimens, in turn, may be more effective, cost-efficient, and appropriate for controlling the rise of resistance than standard regimens.

Acute Disease↗

PubMed2005

Antimicrobial treatment of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a clinical diagnosis that has a significant impact on health care management around the world. Early clinical suspicion and prompt empiric antimicrobial therapies are mandatory in patients with CAP. This article provides a review of recent studies and guidelines addressing antimicrobial therapy for hospitalized patients with CAP.

Anti-Bacterial Agents↗

PubMed2005

Prognosis factors and outcome of community-acquired pneumonia needing mechanical ventilation.

PURPOSE: To evaluate the variables associated with mortality of patients with community-acquired pneumonia who require mechanical ventilation and to determine the attributable morbidity and intensive care unit (ICU) mortality of community-acquired pneumonia. MATERIAL AND METHODS: Retrospective cohort study carried out in 361 ICUs from 20 countries including 124 patients who required mechanical ventilation on the first day of admission to the hospital due to acute respiratory failure secondary to severe community-acquired pneumonia. To assess the factors associated with outcome, a forward stepwise logistic regression analysis was performed, and to determine the attributable mortality of community-acquired pneumonia, a matched study design was used. RESULTS: We found 3 independent variables significantly associated with death in patients with community-acquired pneumonia requiring mechanical ventilation: simplified acute physiological score greater than 45 (odds ratio, 5.5 [95% confidence interval, 1.7-12.3]), shock (odds ratio, 5.7 [95% confidence interval, 1.7-10.1]), and acute renal failure (odds ratio, 3.0 [95% confidence interval, 1.1-4.0]). There was no statistically significant difference in ICU mortality among patients with or without community-acquired pneumonia (32% vs 35%; P=.59). CONCLUSIONS: Community-acquired pneumonia needing mechanical ventilation is not a disease associated with higher mortality. The main determinants of patient outcome were initial severity of illness and the development of shock and/or acute renal failure.

Cohort Studies↗

PubMed2005

Outcome of mechanically ventilated patients who require a tracheostomy.

OBJECTIVE: To estimate the prevalence of, the risk factors associated with, and the outcome of tracheostomy in a heterogeneous population of mechanically ventilated patients. DESIGN: Prospective, observational cohort study. SETTING: A total of 361 intensive care units from 12 countries. PATIENTS: A cohort of 5,081 patients mechanically ventilated for >12 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 546 patients (10.7%) had a tracheostomy during their stay in the intensive care unit. Tracheostomy was performed at a median time of 12 days (interquartile range, 7-17) from the beginning of mechanical ventilation. Variables associated with the performance of tracheostomy were duration of mechanical ventilation, need for reintubation, and neurologic disease as the primary reason of mechanical ventilation. The intensive care unit stay of patients with or without tracheostomy was a median of 21 days (interquartile range, 12-32) vs. 7 days (interquartile range, 4-12; p < .001), respectively, and the hospital stay was a median 36 days (interquartile range, 23-53) vs. 15 days (interquartile range, 8-26; p < .001), respectively. Adjusting by other variables, tracheostomy was independently related with survival in the intensive care unit (odds ratio, 2.22; 95% confidence interval, 1.72-2.86). Mortality in the hospital was similar in both groups (39% vs. 40%, p = .65). CONCLUSIONS: Tracheostomy is a common surgical procedure in the intensive care unit that is associated with a lower mortality in the unit but with a longer stay and a similar mortality in the hospital than in patients without tracheostomy.

Cohort Studies↗

PubMed2005

Airway pressures, tidal volumes, and mortality in patients with acute respiratory distress syndrome.

OBJECTIVE: To determine the usual practice for setting tidal volume and other ventilatory parameters in patients with acute respiratory distress syndrome (ARDS) in the late 1990s and to determine the independent effects of these practices on intensive care unit mortality. DESIGN: Subanalysis of a prospective observational study. Multivariable logistic regression was used to analyze the effects of ventilatory management on mortality. SETTING: A total of 361 intensive care units in 20 countries in March 1998. PATIENTS: A total of 467 mechanically ventilated patients with ARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean tidal volume used in the first week of ARDS was 8.8 mL/kg measured body weight, and there was great variability in these tidal volumes (sd = 2.0). Tidal volumes were significantly lower in patients with (n = 265) than without (n = 202) a recorded plateau pressure (8.6 vs. 9.1 mL/kg, p = .01). The overall intensive care unit mortality rate was 60.2%. In addition to the strong influence of organ failures and higher levels of inspired oxygen, late-onset ARDS (onset after >48 hrs of mechanical ventilation; odds ratio, 2.09) was independently associated with mortality. In addition, lower levels of positive end-expiratory pressure were independently associated with higher mortality (odds ratio, 0.91; 1 cm of H2O increments). Neither inspiratory pressures nor tidal volumes were independently associated with mortality, and there was no evidence of increased mortality with the use of lower inspiratory pressures. CONCLUSIONS: This descriptive study demonstrated considerable interpatient variability in tidal volumes during the study period. In addition to traditional prognostic indicators, timing of ARDS onset and the use of low levels of positive end-expiratory pressure or no positive end-expiratory pressure during the first week may adversely influence outcome in ARDS patients.

Adult↗

PubMed2005

Use of sedatives and neuromuscular blockers in a cohort of patients receiving mechanical ventilation.

OBJECTIVE: To describe the use of sedatives and neuromuscular blocking agents (NMBs) and their impact in outcome in an international cohort of patients receiving mechanical ventilation. METHODS: We analyzed the database of a prospective, multicenter cohort of 5,183 adult patients who received mechanical ventilation for > 12 h. We considered that a patient received a given agent when it was administered for at least 3 h in a 24-h period. RESULTS: A total of 3,540 patients (68%; 95% confidence interval [CI], 67 to 69%) received a sedative at any time while receiving mechanical ventilation. The median number of days of use was 3 (interquartile range [IQR], 2 to 6 days). The persistent use of sedative was associated with more days of mechanical ventilation (median, 4 days [IQR, 2 to 8 days], vs 3 days [IQR, 2 to 4 days] in patients who did not receive sedatives [p < 0.001]); more weaning days (median, 2 days [IQR, 1 to 3 days], vs 2 days [IQR, 1 to 5 days] in patients who did not receive sedatives [p < 0.001]); and longer length of stay in the ICU (median, 8 days [IQR, 5 to 15 days], vs 5 days [IQR, 3 to 9 days] in patients who did not receive sedatives [p < 0.001]). Six hundred eighty-six patients (13%; 95% CI, 12 to 14%) received an NMB for at least 1 day. The median number of days of use was 2 (IQR, 1 to 4 days). The administration of an NMB was independently related with age, a normal previous functional status, main reason of mechanical ventilation (patients with ARDS received more NMBs), and with patient management (patients requiring permissive hypercapnia, prone position, high level of positive end-expiratory pressure, and high airways pressure). CONCLUSIONS: The use of sedatives is very common, and their use is associated with a longer duration of mechanical ventilation, weaning time, and stay in the ICU. NMBs are used in 13% of the patients and are associated with longer duration of mechanical ventilation, weaning time, stay in the ICU, and higher mortality.

Cohort Studies↗

PubMed2005

A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia.

CONTEXT: Antimicrobial cardiac safety is of particular concern during the treatment of community-acquired pneumonia (CAP) in elderly patients, due to the presence of comorbid conditions and the use of multiple medications that may individually or synergistically affect cardiac repolarization. STUDY OBJECTIVE: To assess the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with CAP. DESIGN AND SETTING: Prospective, randomized, double-blind trial conducted at 47 hospitals in the United States. PATIENTS: Subjects > or = 65 years old with clinical signs/symptoms of CAP requiring initial parenteral therapy, including those with comorbidities. The safety population included 394 patients: 51.3% male; 85.3% white; mean age, 77.8 years. Two-thirds of the patients were > 75 years old, and 74.1% had a history of cardiac disease. INTERVENTIONS: Patients received IV/oral moxifloxacin (400 mg qd) or IV/oral levofloxacin (500 mg qd) for 7 to 14 days. Safety evaluations included 72 h of digital continuous 12-lead Holter monitoring, 12-lead ECGs at baseline and at maximum serum concentration on day 3, and adverse events. MAIN OUTCOME MEASURES: The primary safety end point was a composite of ventricular arrhythmia events based on Holter monitoring. RESULTS: Holter monitor data were available for 387 patients (192 receiving moxifloxacin and 195 receiving levofloxacin). Sixteen moxifloxacin-treated patients (8.3%) and 10 levofloxacin-treated patients (5.1%) had a primary composite cardiac event (p = 0.29); most events were nonsustained ventricular tachycardia (VT) [14 patients receiving moxifloxacin, 7.3%; and 10 patients receiving levofloxacin, 5.1%]. One moxifloxacin-treated patient had sustained monomorphic VT (> 30 s), and one levofloxacin-treated patient had torsade de pointes. Mean +/- SD QTc (Fridericia formula) change on day 3 was + 6.4 +/- 23.2 ms for moxifloxacin and - 2.5 +/- 22.9 ms for levofloxacin (p = 0.04). No deaths clearly related to study drugs occurred during the observation period. CONCLUSIONS: IV/oral moxifloxacin, although known to cause QTc interval prolongation, has a comparable cardiac rhythm safety profile to IV/oral levofloxacin in high-risk elderly patients with CAP.

Aged↗

PubMed2004

Effects of guideline-concordant antimicrobial therapy on mortality among patients with community-acquired pneumonia.

PURPOSE: National practice guidelines have recommended specific initial empiric antimicrobial regimens for patients with community-acquired pneumonia. Our aim was to determine the association between the use of guideline-concordant antimicrobial therapy and 30-day mortality in patients with pneumonia. METHODS: We conducted a retrospective cohort study at two tertiary teaching hospitals. Eligible patients were admitted with a diagnosis of community-acquired pneumonia, had a chest radiograph consistent with pneumonia, and had a discharge diagnosis of pneumonia. All eligible patients were identified and a random sample was abstracted. We determined whether the use of guideline-concordant antibiotics was associated with 30-day mortality in an analysis that adjusted for potential confounders using propensity scores. RESULTS: Information was obtained on 420 patients with pneumonia. The mean (+/- SD) age was 63 +/- 16 years, 355 were men, and 82 patients were initially admitted to the intensive care unit. At 30 days after presentation, 41 patients (9.8%) had died: 21 of 97 (21.7%) in the non-guideline-concordant group and 20 of 323 (6.2%) in the guideline-concordant group. Antibiotics were concordant with national guidelines in 323 patients. In the regression analysis, after adjustment for the propensity score, failure to comply with antimicrobial therapy guidelines was associated with increased 30-day mortality (odds ratio = 5.7; 95% confidence interval: 2.0 to 16.0). CONCLUSION: Receipt of antimicrobial regimens concordant with national published guidelines may reduce 30-day mortality among patients hospitalized with pneumonia.

Aged↗

PubMed2004

Noninvasive positive-pressure ventilation for respiratory failure after extubation.

BACKGROUND: The need for reintubation after extubation and discontinuation of mechanical ventilation is not uncommon and is associated with increased mortality. Noninvasive positive-pressure ventilation has been suggested as a promising therapy for patients with respiratory failure after extubation, but a single-center, randomized trial recently found no benefit. We conducted a multicenter, randomized trial to evaluate the effect of noninvasive positive-pressure ventilation on mortality in this clinical setting. METHODS: Patients in 37 centers in eight countries who were electively extubated after at least 48 hours of mechanical ventilation and who had respiratory failure within the subsequent 48 hours were randomly assigned to either noninvasive positive-pressure ventilation by face mask or standard medical therapy. RESULTS: A total of 221 patients with similar baseline characteristics had been randomly assigned to either noninvasive ventilation (114 patients) or standard medical therapy (107 patients) when the trial was stopped early, after an interim analysis. There was no difference between the noninvasive-ventilation group and the standard-therapy group in the need for reintubation (rate of reintubation, 48 percent in both groups; relative risk in the noninvasive-ventilation group, 0.99; 95 percent confidence interval, 0.76 to 1.30). The rate of death in the intensive care unit was higher in the noninvasive-ventilation group than in the standard-therapy group (25 percent vs. 14 percent; relative risk, 1.78; 95 percent confidence interval, 1.03 to 3.20; P=0.048), and the median time from respiratory failure to reintubation was longer in the noninvasive-ventilation group (12 hours vs. 2 hours 30 minutes, P=0.02). CONCLUSIONS: Noninvasive positive-pressure ventilation does not prevent the need for reintubation or reduce mortality in unselected patients who have respiratory failure after extubation.

Aged↗

PubMed2004

Outcome of older patients receiving mechanical ventilation.

OBJECTIVE: To determine the threshold of age that best discriminates the survival of mechanically ventilated patients and to estimate the outcome of mechanically ventilated older patients. DESIGN: International prospective cohort study. SETTING: Three hundred sixty-one intensive care units from 20 countries. PATIENTS AND PARTICIPANTS. Five thousand one hundred eighty-three patients mechanically ventilated for more than 12 h. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Recursive partitioning and logistic regression were used and an outcome model was derived and validated using independent subgroups of the cohort. Two age thresholds (43 and 70 years) were found, by partitioning recursive analysis, to be associated with outcome. This study focuses on the analysis of patients older than 43 years of age, divided in two subgroups: between 43 and 70 years (middle age group) and older than 70 years (elderly group). Survival in hospital was 45% (95% C.I.: 43-48) for the elderly group and 55% (53-57) for the middle age group ( p<0.001). Advanced age was not associated with prolongation of mechanical ventilation, weaning or length of stay in the ICU and in hospital ( p>0.05). Variables associated with mortality in the elderly were: acute renal failure, shock, Simplified Acute Physiology Score II and a ratio of PaO(2) to FIO(2) more than 150. CONCLUSIONS: Older mechanically ventilated patients (age >70 years) had a lower ICU and hospital survival, but the duration of mechanical ventilation, ICU and hospital stay were similar to younger patients. Factors associated with the highest risk of mortality in patients older than 70 were the development of complications during the course of mechanical ventilation, such as acute renal failure and shock.

Acute Kidney Injury↗

PubMed2004

Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients.

OBJECTIVE: To determine the incidence, risk factors, and outcome of barotrauma in a cohort of mechanically ventilated patients where limited tidal volumes and airway pressures were used. DESIGN AND SETTING: Prospective cohort of 361 intensive care units from 20 countries. PATIENTS AND PARTICIPANTS: A total of 5183 patients mechanically ventilated for more than 12 h. MEASUREMENTS AND RESULTS: Baseline demographic data, primary indication for mechanical ventilation, daily ventilator settings, multiple-organ failure over the course of mechanical ventilation and outcome were collected. Barotrauma was present in 154 patients (2.9%). The incidence varied according to the reason for mechanical ventilation: 2.9% of patients with chronic obstructive pulmonary disease; 6.3% of patients with asthma; 10.0% of patients with chronic interstitial lung disease (ILD); 6.5% of patients with acute respiratory distress syndrome (ARDS); and 4.2% of patients with pneumonia. Patients with and without barotrauma did not differ in any ventilator parameter. Logistic regression analysis identified as factors independently associated with barotrauma: asthma [RR 2.58 (1.05-6.50)], ILD [RR 4.23 (95%CI 1.78-10.03)]; ARDS as primary reason for mechanical ventilation [RR 2.70 (95%CI 1.55-4.70)]; and ARDS as a complication during the course of mechanical ventilation [RR 2.53 (95%CI 1.40-4.57)]. Case-control analysis showed increased mortality in patients with barotrauma (51.4 vs 39.2%; p=0.04) and prolonged ICU stay. CONCLUSIONS: In a cohort of patients in whom airway pressures and tidal volume are limited, barotrauma is more likely in patients ventilated due to underlying lung disease (acute or chronic). Barotrauma was also associated with a significant increase in the ICU length of stay and mortality.

Adult↗

PubMed2004

Clarithromycin in 2003: sustained efficacy and safety in an era of rising antibiotic resistance.

Data from surveillance studies show increasing prevalence of respiratory pathogens resistant to commonly used antibiotics. Thus, a Medline search was conducted to identify studies of clarithromycin, especially those addressing macrolide resistance. Changing trends of in vitro susceptibility have not affected clinical efficacy with clarithromycin. Over the last 12 years, clarithromycin study results have shown consistent rates of clinical cure and bacteriological eradication, which are similar to those observed with comparator agents. The incidence of clarithromycin treatment failure in patients infected with Streptococcus pneumoniae is substantially less than that predicted by macrolide resistance rates from surveillance programmes. In summary, despite widespread use since its introduction, clarithromycin remains active both in vitro and in vivo against clinically relevant respiratory tract pathogens.

Anti-Bacterial Agents↗

PubMed2004

Initial treatment regimen and risk of hospitalization in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVES: Compare hospitalization risk of various initial treatment regimens for COPD. DESIGN: Retrospective observational cohort design. SETTING: Patients enrolled in 24 different managed care plans across the United States during 1997-2000. PATIENTS: Aged at least 45 years with a primary diagnosis of COPD identified. Initiation date was the date the first inhaler was dispensed. Patients were required to have filled this prescription within 60 days of the first documented COPD diagnosis in the database. INTERVENTIONS: Five therapy cohorts were identified 1) ipratropium alone or in combination with albuterol (IPR), 2) long-acting beta agonists (LABA), 3) inhaled corticosteroid (ICS), 4) ICS+IPR and 5) ICS+LABA. MEASUREMENTS: Subjects were observed for 12 months or until a COPD-related hospitalization was observed, whichever came first. A sensitivity analysis was conducted by varying the observation period from >60, >90 and >180 days to determine if this would impact the results. RESULTS: 3616 patients were identified, 1754 (49%) on IPR alone, 1032 (29%) on ICS alone, 357 (10%) on ICS+IPR, 266 (7%) on LABA alone and 207 (6%) on ICS+LABA. Compared with IPR alone, patients in the ICS alone and ICS plus LABA groups had a 36% and 47% reductions in the risk of a COPD hospitalization, (HR: 0.643; 95% CI 0.512, 0.808 and HR: 0.533; 95% CI 0.328, 0.865) respectively. CONCLUSIONS: The results of this analysis suggest that initial treatment with an ICS alone or in combination with a LABA , compared to IPR alone, was associated with a significant decrease in the risk of COPD hospitalization 12 months following the start of therapy independent of concomitant asthma diagnosis. Similar outcomes were observed when the observation period was varied from >60, >90 and >180 days.

Adrenergic beta-Agonists↗

PubMed2004

Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

OBJECTIVE: To assess the hemodynamic effects of the nitric oxide synthase inhibitor 546C88 in patients with septic shock, although this was not a stated aim of the protocol. The predefined primary efficacy objective of the protocol was resolution of shock determined at the end of a 72-hr treatment period. DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive care units in Europe, North America, and Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for vasopressors, systemic and pulmonary hemodynamics, indices of oxygen transport, and plasma concentrations of arginine and nitrate were assessed over time. The median mean arterial pressure for both groups was maintained > or =70 mm Hg. There was an early increase in systemic and pulmonary vascular tone and oxygen extraction, whereas both cardiac index and oxygen delivery decreased for patients in the 546C88 cohort. Although these parameters subsequently returned toward baseline values, the observed differences between the treatment groups, except for pulmonary vascular resistance and oxygen extraction, persisted throughout the treatment period, despite a reduced requirement for vasopressors in the 546C88 cohort. These changes were associated with a reduction in plasma nitrate concentrations, which were elevated in both groups before the start of therapy. CONCLUSIONS: The nitric oxide synthase inhibitor 546C88 can reduce the elevated plasma nitrate concentrations observed in patients with septic shock. In this study, treatment with 546C88 for up to 72 hrs was associated with an increase in vascular tone and a reduction in both cardiac index and oxygen delivery. The successful maintenance of a target mean arterial blood pressure > or =70 mm Hg was achieved with a reduction in the requirement for, or withdrawal of, conventional inotropic vasoconstrictor agents (i.e., dopamine and norepinephrine). There were no substantive untoward consequences accompanying these hemodynamic effects. An international, randomized, double-blind, placebo-controlled phase III study has since been conducted in patients with septic shock. Recruitment into the study was discontinued due to the emergence of increased mortality in the 546C88-treated group.

Adult↗