Burden of pneumococcal community-acquired pneumonia in adults across Europe: A literature review.

Background: The burden of community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae (pneumococcus) among adults in Europe is poorly defined.

Methods: Structured searches of PubMed were conducted to identify the incidence of pneumococcal CAP among adults across Europe.

Results: The overall incidence rates for CAP was 68-7000 per 100,000 and the incidence in hospitalised CAP cases of all causes was 16-3581 per 100,000.

Community-acquired pneumonia in adults: Highlighting missed opportunities for vaccination.

Pneumococcal pneumonia remains a clear unmet medical need for adults worldwide. Despite advances in vaccine technology, vaccination coverage remains low, putting many people at risk of significant morbidity and mortality. The herd effect seen with paediatric vaccination is not enough to protect all older and vulnerable people in the community, and more needs to be done to increase the uptake of pneumococcal vaccination in adults.

A Retrospective Study of the Clinical Burden of Hospitalized All-Cause and Pneumococcal Pneumonia in Canada.

Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed.

Longitudinal DRG-based survey of all-cause and pneumococcal pneumonia and meningitis for inpatients in France (2005-2010).

Objective: This population-based retrospective study quantified the burden of all-cause and pneumococcal pneumonia and meningitis in the Rhône-Alpes region of France from 2005 to 2010, when the 7-valent pneumococcal conjugate vaccine uptake increased from 50 to>90% in children.

Patients And Methods: Hospital admission data was obtained from the French Diagnosis Related Groups program database (French acronym PMSI). Patients were residents of the Rhône-Alpes region hospitalized for the diseases of interest during 2005-2010.

Which individuals are at increased risk of pneumococcal disease and why? Impact of COPD, asthma, smoking, diabetes, and/or chronic heart disease on community-acquired pneumonia and invasive pneumococcal disease.

Pneumococcal disease (including community-acquired pneumonia and invasive pneumococcal disease) poses a burden to the community all year round, especially in those with chronic underlying conditions. Individuals with COPD, asthma or who smoke, and those with chronic heart disease or diabetes mellitus have been shown to be at increased risk of pneumococcal disease compared with those without these risk factors. These conditions, and smoking, can also adversely affect patient outcomes, including short-term and long-term mortality rates, following pneumonia.

PCVs in individuals at increased risk of pneumococcal disease: a literature review.

The use of pneumococcal conjugate vaccine (PCV) in childhood pneumococcal immunization programs successfully reduced the incidence of pneumococcal disease in children. Nonetheless, there remains a high burden of pneumococcal disease in adults, especially the elderly, and children/adults with chronic medical conditions. Two pneumococcal vaccines are currently available for adults at risk of pneumococcal disease: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the more recently licensed PCV13.

Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot infections with and without osteomyelitis.

A phase 3, randomized, double-blind trial was conducted in subjects with diabetic foot infections without osteomyelitis (primary study) or with osteomyelitis (substudy) to determine the efficacy and safety of parenteral (intravenous [iv]) tigecycline (150 mg once-daily) versus 1 g once-daily iv ertapenem ± vancomycin. Among 944 subjects in the primary study who received ≥1 dose of study drug, >85% had type 2 diabetes; ~90% had Perfusion, Extent, Depth/tissue loss, Infection, and Sensation infection grade 2 or 3; and ~20% reported prior antibiotic failure. For the clinically evaluable population at test-of-cure, 77.

A retrospective study of hospitalized pneumonia in two Polish counties (2006-2008).

Introduction: In Poland, multi-cause pneumonia is not well characterized, and there is limited pneumococcal vaccination in the youngest and oldest age groups. The goal of this study was to assess hospitalized pneumonia across all age groups in two Polish counties.

Material And Methods: Using electronic administrative databases, cases were identified as county residents hospitalized at Chrzanów and Inowrocław County Hospitals from 2006-2008, assigned a diagnosis of pneumonia.

Tigecycline versus levofloxacin in hospitalized patients with community-acquired pneumonia: an analysis of risk factors.

Introduction: This study was conducted to evaluate the efficacy of tigecycline (TGC) versus levofloxacin (LEV) in hospitalized patients with community-acquired pneumonia (CAP) using pooled data and to perform exploratory analyses of risk factors associated with poor outcome.

Materials And Methodology: Pooled analyses of 2 phase 3 studies in patients randomized to intravenous (IV) TGC (100 mg, then 50 mg q12h) or IV LEV (500 mg q24h or q12h). Clinical responses at test of cure visit for the clinically evaluable (CE) and clinical modified intention to treat populations were assessed for patients with risk factors including aged ≥65 years, prior antibiotic failure, bacteremia, multilobar disease, chronic obstructive pulmonary disease, alcohol abuse, altered mental status, hypoxemia, renal insufficiency, diabetes mellitus, white blood cell count >30 x 10(9)/L or <4 x 10(9)/L, CURB-65 score ≥2, Fine score category of III to V and at least 2 clinical instability criteria on physical examination.

Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia.

In a previous phase 3 study, the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin (imipenem/cilastatin). We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia. This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia.

Pharmacokinetics and safety profile of tigecycline in children aged 8 to 11 years with selected serious infections: a multicenter, open-label, ascending-dose study.

Background: Tigecycline, a broad-spectrum antibiotic used for treating serious bacterial infections in adults, may be suitable for pediatric use once an appropriate dosage is determined.

Objective: The aim of this study was to assess the pharmacokinetic (PK) properties, safety profile, and descriptive efficacy of tigecycline.

Methods: In this Phase II, multicenter, open-label clinical trial, children aged 8 to 11 years with community-acquired pneumonia (CAP), complicated intra-abdominal infection (cIAI), or complicated skin and skin structure infections (cSSSI) were administered tigecycline 0.

Pharmacological and patient-specific response determinants in patients with hospital-acquired pneumonia treated with tigecycline.

Pharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) who were enrolled in a phase 3 clinical trial were integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological responses, based on data from 61 evaluable HAP patients who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and for whom there were adequate clinical, pharmacokinetic, and response data. The final multivariable logistic regression model for clinical response contained albumin and the ratio of the free-drug area under the concentration-time curve from 0 to 24 h (fAUC(0-24)) to the MIC (fAUC(0-24):MIC ratio).

Pharmacokinetics-pharmacodynamics of tigecycline in patients with community-acquired pneumonia.

Exposure-response analyses for efficacy and safety were performed for tigecycline-treated patients suffering from community-acquired pneumonia. Data were collected from two randomized, controlled clinical trials in which patients were administered a 100-mg loading dose followed by 50 mg of tigecycline every 12 h. A categorical endpoint, success or failure, 7 to 23 days after the end of therapy (test of cure) and a continuous endpoint, time to fever resolution, were evaluated for exposure-response analyses for efficacy.

Efficacy and safety of tigecycline monotherapy compared with vancomycin-aztreonam in the treatment of complicated skin and skin structure infections in patients from India and Taiwan.

Background: To compare the monotherapy of tigecycline with vancomycin-aztreonam in hospitalized patients from India and Taiwan with complicated skin and skin structure infections (cSSSIs).

Methods: Safety and efficacy data were analyzed for Indian (n = 86) and Taiwanese (n = 41) patients hospitalized with cSSSIs who participated in two international Phase 3, randomized, double-blind studies.

Results: Patients were treated for 5-14 days.

Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia.

To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients, a phase 3, multicenter, randomized, double-blind, study evaluated 945 patients. Coprimary end points were clinical response in clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure. Cure rates were 67.

Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia.

Background: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP.

Methods: In this prospective, double-blind, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy.

Tigecycline versus levofloxacin for the treatment of community-acquired pneumonia: European experience.

Tigecycline (TGC), a first-in-class glycylcycline that has been approved for treating complicated skin and skin structure infections and complicated intra-abdominal infections, has an expanded spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, including resistant strains. The purpose of this study was to compare the efficacy and safety of TGC with levofloxacin (LEV) in adult hospitalised patients with community-acquired pneumonia (CAP) in a randomised, doubleblind, phase 3 multinational trial. This analysis evaluated TGC efficacy and safety in the European region.

Overview of tigecycline efficacy and safety in the treatment of complicated skin and skin structure infections - a European perspective.

In a randomized, double-blind, multicenter, multinational, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. Three hundred eighty-five (385) were from Europe. The primary endpoint was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable populations at the test-of-cure visit 12 to 92 days after the last dose.

The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections - the European experience.

The polymicrobial nature of complicated intra-abdominal infections makes these infections particularly challenging to treat. The initial selection of antimicrobial therapy is therefore extremely important. Inappropriate empiric antimicrobial therapy has been shown to delay clinical resolution, increase length of hospital stay, and increase the risk of mortality.

A Phase 3, open-label, non-comparative study of tigecycline in the treatment of patients with selected serious infections due to resistant Gram-negative organisms including Enterobacter species, Acinetobacter baumannii and Klebsiella pneumoniae.

Objectives: To evaluate the efficacy and safety of tigecycline in patients with selected serious infections caused by resistant Gram-negative bacteria, or failures who had received prior antimicrobial therapy or were unable to tolerate other appropriate antimicrobials. Secondary objectives included an evaluation of the microbiological efficacy of tigecycline and in vitro activity of tigecycline for resistant Gram-negative bacteria.

Methods: This open-label, Phase 3, non-comparative, multicentre study assessed the efficacy and safety of intravenous tigecycline (100 mg initially, then 50 mg 12 hourly for 7-28 days) in hospitalized patients with serious infections including complicated intra-abdominal infection; complicated skin and skin structure infection (cSSSI); community-acquired pneumonia (CAP); hospital-acquired pneumonia, including ventilator-associated pneumonia; or bacteraemia, including catheter-related bacteraemia.

Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a Phase 3, multicentre, double-blind, randomized study.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are causing serious nosocomial infections. Tigecycline was evaluated in hospitalized patients with MRSA or VRE infection.

Patients And Methods: A randomized (3:1), double-blind, multicentre, Phase 3 study compared the safety and efficacy of tigecycline with vancomycin or linezolid in hospitalized patients with MRSA or VRE infection, respectively.

Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia.

Tigecycline (TGC), a glycylcycline, has expanded activity against Gram-positive and Gram-negative, anaerobic, and atypical bacteria. Two phase 3 studies were conducted. Hospitalized patients with community-acquired pneumonia (CAP) were randomized to intravenous (IV) TGC (100 mg followed by 50 mg bid) or IV levofloxacin (LEV) (500 mg bid).

Tigecycline is efficacious in the treatment of complicated intra-abdominal infections.

Background: Empiric treatment of complicated intra-abdominal infections (cIAI) represents a clinical challenge because of the diverse bacteriology and the emergence of bacterial resistance. The efficacy and safety of tigecycline (TGC), a first-in-class, expanded broad-spectrum glycylcycline antibiotic, were compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.

Methods: In this prospective, double-blind, phase 3, multinational trial, patients were randomly assigned to intravenous (i.

Safety and efficacy of tigecycline in treatment of skin and skin structure infections: results of a double-blind phase 3 comparison study with vancomycin-aztreonam.

In a randomized, double-blind, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. The primary end point was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable (CE) populations at the test-of-cure visit 12 to 92 days after the last dose. The microbiologic response at the test-of-cure visit was also assessed.