The impact of empiric antimicrobial therapy with a β-lactam and fluoroquinolone on mortality for patients hospitalized with severe pneumonia

INTRODUCTION: National clinical practice guidelines have recommended specific empiric antimicrobial regimes for patients with severe community-acquired pneumonia. However, evidence confirming improved mortality with many of these regimes is lacking. Our aim was to determine the association between the empiric use of a β-lactam with fluoroquinolone, compared with other recommended antimicrobial therapies, and mortality in patients hospitalized with severe community-acquired pneumonia. METHODS: A retrospective observational study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of community-acquired pneumonia and had a chest X-ray and a discharge ICD-9 diagnosis consistent with this. Subjects were excluded if they received 'comfort measures only' during the admission, had been transferred from another acute care hospital, did not meet criteria for severe pneumonia, or were treated with non-guideline-concordant antibiotics. A multivariable logistic regression model was used to assess the association between 30-day mortality and the use of a β-lactam antibiotic with a fluoroquinolone compared with other guideline-concordant therapies, after adjustment for potential confounders including a propensity score. RESULTS: Data were abstracted on 172 subjects at the two hospitals. The mean age was 63.5 years (SD 15.0). The population was 88% male; 91% were admitted through the emergency department and 62% were admitted to the intensive care unit within the first 24 hours after admission. Mortality was 19.8% at 30 days. After adjustment for potential confounders the use of a β-lactam with a fluoroquinolone (odds ratio 2.71, 95% confidence interval 1.2 to 6.1) was associated with increased mortality. CONCLUSION: The use of initial empiric antimicrobial therapy with a β-lactam and a fluoroquinolone was associated with increased short-term mortality for patients with severe pneumonia in comparison with other guideline-concordant antimicrobial regimes. Further research is needed to determine the range of appropriate empiric antimicrobial therapies for patients with severe community-acquired pneumonia

A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilatorassociated pneumonia

INTRODUCTION: The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria. METHODS: This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011). RESULTS: The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0). CONCLUSIONS: Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0058969

Clinical evaluation of the role of ceftaroline in the management of community acquired bacterial pneumonia

Ceftaroline fosamil (ceftaroline) was recently approved for the treatment of community- acquired pneumonia (CAP) and complicated skin infections. This newly developed cephalosporin possesses a broad spectrum of activity against gram-positive and gram-negative bacteria. Most importantly, ceftaroline demonstrates potent in vitro antimicrobial activity against multi-drug resistant Streptococcus pneumoniae and methicillin-resistant strains of Staphylococcus aureus. In two Phase III, double-blinded, randomized, prospective trials (FOCUS 1 and FOCUS 2), ceftaroline was shown to be non-inferior to ceftriaxone for the treatment of CAP in hospitalized patients. Ceftaroline exhibits low resistance rates and a safety profile similar to that of other cephalosporins. In this review, we will evaluate the pharmacological characteristics, safety, antimicrobial properties, and efficacy of ceftaroline and its applications in the treatment of CAP

Short Duration of Antibiotic Therapy in Hospitalized Patients with Community-Acquired Pneumonia: Results from the CAPO International Cohort Study

Introduction: Experts suggest a short duration of antibiotic therapy (DOT) in responding patients with community-acquired pneumonia (CAP). The aim of this study was to evaluate clinical outcomes after hospital discharge among patients treated with short-course antibiotic therapy (SCT) vs. long-course antibiotic therapy (LCT) for CAP. Methods: A secondary analysis of the Community-Acquired Pneumonia Organization (CAPO) database from January 2007 to June 2013 was performed, including hospitalized CAP patients who reached clinical stability within 5 days. Two groups were identified: patients who were treated with antibiotic therapy for a total duration of 5 days or less (SCT Group) vs. longer than 5 days (LCT Group). Rehospitalization and mortality were evaluated at 30 days after discharge. Results: 1,849 patients were enrolled (58% males; median age: 65 years), 179 (10%) were included in the SCT and 1,670 (90%) in the LTC group. Median DOT was 5 days in the SCT and 10 days in the LTC group, p Conclusions: A duration of antibiotic therapy of ≤ 5 days does not adversely impact clinical outcomes at 30-days after discharge compared to \u3e5 days in patients who reached early clinical stability

Do Antiplatelet Medications Prevent Poor Clinical Outcomes in Patients With Community-Acquired Pneumonia? Results From the Community-Acquired Pneumonia Organization International Cohort Study

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Correlation of Obesity With Outcomes in Hospitalized Patients With Community-Acquired Pneumonia: Results From the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

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Clinical Characteristics and Outcomes of Patients With Community-Acquired Pneumonia—Real-Life Versus Food and Drug Administration (FDA) Trials: Results From the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

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