Miguel Sánchez García

Efficacy of tigecycline for the treatment of complicated intra-abdominal infections in real-life clinical practice from five European observational studies

OBJECTIVES Tigecycline is a broad-spectrum antibiotic approved for the treatment of complicated intra-abdominal infections (cIAIs). The efficacy of tigecycline when administered as monotherapy or in combination with other antibacterials in the treatment of cIAIs in routine clinical practice is described. PATIENTS AND METHODS Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). RESULTS A total of 785 cIAI patients who received tigecycline were included (mean age 63.1 ± 14.0 years). Of these, 56.6% were in intensive care units, 65.6% acquired their infection in hospital, 88.1% had at least one comorbidity and 65.7% had secondary peritonitis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 16.9 ± 7.6 (n = 614) and 7.0 ± 4.2 (n = 108), respectively, indicating high disease severity. Escherichia coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%) were the most frequently isolated pathogens; 49.1% of infections were polymicrobial and 17.5% were due to resistant pathogens. Overall, 54.8% (n = 430) received tigecycline as monotherapy and 45.2% (n = 355) as combination therapy for a mean duration of 10.6 days. Clinical response rates at the end of treatment were 77.4% for all patients (567/733), 80.6% for patients who received tigecycline as monotherapy (329/408), 75.2% for patients with a nosocomial infection (354/471), 75.8% for patients with an APACHE II score >15 (250/330) and 54.2% (32/59) for patients with a SOFA score ≥ 7. CONCLUSIONS In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cIAI with a high severity of illness.

Prescription behaviours for tigecycline in real-life clinical practice from five European observational studies

OBJECTIVES There is limited information on the use of tigecycline in real-life clinical practice. This analysis aims to identify and understand tigecycline prescribing patterns and associated patient outcomes for approved indications. PATIENTS AND METHODS A pooled analysis of patient-level data collected on the prescription of tigecycline in five European observational studies (July 2006 to October 2011) was conducted. RESULTS A total of 1782 patients who received tigecycline were included in the analysis. Of these patients, 61.6% were male, the mean age was 63.4 ± 14.7 years, 56.4% were in intensive care units, 80.2% received previous antibiotic treatment and 91% had one or more comorbid conditions. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 17.7 ± 7.9 and 7.0 ± 4.0, respectively. The majority of patients (58.3%) received tigecycline for treatment of complicated skin and soft-tissue infections (cSSTIs; n = 254) or complicated intra-abdominal infections (cIAIs; n = 785). Tigecycline was given at the standard dose (100 mg plus 50 mg twice daily) to 89.3% of patients for a mean duration of 11.1 ± 6.4 days. The main reasons for prescribing tigecycline were failure of previous therapy (46.1%), broad-spectrum antibiotic coverage (41.4%) and suspicion of a resistant pathogen (39.3%). Tigecycline was prescribed first-line in 36.3% of patients and as monotherapy in 50.4%. Clinical response rates to treatment with tigecycline alone or in combination were 79.6% (183/230; cSSTIs) and 77.4% (567/733; cIAIs). CONCLUSIONS Although tigecycline prescription behaviour showed some heterogeneity across the study sites, these results confirm a role for tigecycline in real-life clinical practice for the treatment of complicated infections, including those in critically ill patients, across Europe.

Partial Splenic Embolization for the Treatment of Hypersplenism in Liver Transplanted Patients with Hepatitis C Virus Recurrence before peg-interferon Plus Ribavirin

Reinfection of the graft follows liver transplantation (LT) patients with HCV, with an accelerated course of the disease due to immunosuppressive treatment (1). Progression to cirrhosis is increased, more than 20% of patients present severe graft damage at 5 years post-LT (2), and the rate of death and allograft failure is increased when compared with other indications (3). The lack of an efficient strategy to prevent graft reinfection and the aggressive course of HCV after LT indicate the need for an effective antiviral therapy able to preserve the viability of the graft. Recent data on the use of peg-IFN plus ribavirin (RBV) after LT are encouraging, with rates of sustained virological response (SVR) over 30%, improved graft function, and a beneficial effect on the histological disease progression (4). Therapy, however, is limited by the high rate of peg-IFN and/or RBV-related hematological toxicity leading to dose reductions and/or administration of hematopoietic growth factors, such as erythropoietin (EPO), or granulocyte-colonies stimulating factor (G-CSF) (5). To date, severe thrombocytopenia remains as an absolute contraindication for HCV therapy. Partial splenic embolization (PSE) seems to be an effective alternative to surgical splenectomy for the treatment of hematologic disorders in cirrhotic patients with hypersplenism, especially against thrombocytopenia (6), and improves liver functions (7). We aimed to evaluate the safety and effectiveness of PSE before peg-IFN/RBV in three liver recipients with HCV recurrence and hypersplenism. After pneumococcal vaccination, PSE was performed under intravenous antibiotic, sedative, and antiemetic therapy. A femoral artery approach was used for superselective distal catheterization of the splenic artery, with injection of polyvinyl-alcohol particles (355 to 500 ) suspended in a solution of penicillin, gentamicin, and non-ionic iodine contrast, to obtain an splenic infarction ratio between 50% and 80%. Contrast-enhanced abdominal CT scan and Doppler ultrasound studies were performed before PSE and during follow-up, to assess the presence of complications. At a mean of 12 weeks after PSE all patients started weight-adjusted RBV plus peg-IFN-2b and were assessed in a monthly basis, including

Resistance mechanisms and epidemiology of multiresistant pathogens in Europe and efficacy of tigecycline in observational studies

OBJECTIVES Antimicrobial drug resistance is a growing problem in Europe and, even with differences in epidemiology, it is of great concern. The treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) is hindered further by pathogens that are resistant to methicillin, carbapenems, third-generation cephalosporins and glycopeptides. PATIENTS AND METHODS An analysis of the microbiological results from five European observational studies (July 2006 to October 2011) evaluating the efficacy of tigecycline (prescribed as monotherapy or in combination with other antibacterials) for the treatment of cSSTI and cIAI is presented. RESULTS In total, 213 cSSTI and 623 cIAI patients were included; 34.4% and 56.6%, respectively, were critically ill in intensive care units. At baseline, at least one pathogen was isolated in 167 (78.4%) cSSTI and 464 (74.5%) cIAI patients, and 32.9% and 49.1% of infections were polymicrobial. In cSSTI, Staphylococcus aureus and Escherichia coli (52.7% and 18.0%, respectively) were the most frequently isolated pathogens, whereas in cIAI most infections were due to E. coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%). Clinical response was observed in >80% of patients with E. coli in both cIAI and cSSTI. In cSSTI patients, the clinical response rate to S. aureus was 80.8%. For cIAI, 77.4% of E. faecium and 79.5% of E. faecalis patients responded to treatment. CONCLUSIONS Tigecycline when given alone or in combination with other antibacterials appeared to be efficacious against multiple pathogens, affirming its role in real-life clinical practice as a broad-spectrum antibacterial for the treatment of patients with cSSTI and cIAI, including the critically ill, across Europe.

Safety and tolerability of tigecycline for the treatment of complicated skin and soft-tissue and intra-abdominal infections: an analysis based on five European observational studies

OBJECTIVES Tigecycline is approved for the treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) in adults. In this analysis the safety and tolerability profile of tigecycline (used alone or in combination) for the treatment of patients with approved indications of cSSTI and cIAI were examined under real-life clinical conditions. PATIENTS AND METHODS Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). A total of 254 cSSTI and 785 cIAI patients were included. The mean age was 63 years; 34.4% and 56.6% were in intensive care units, 90.9% and 88.1% had at least one comorbidity and mean Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the beginning of treatment were 15.0 ± 7.9 and 16.9 ± 7.6, respectively. RESULTS Data on adverse events (AEs) were available for 198 cSSTI and 590 cIAI patients in three studies. Nausea and vomiting were reported in ≤ 2% of patients. The most common serious AEs were multi-organ failure (4.0% and 10.0% in cSSTI and cIAI patients, respectively) and sepsis (4.0% and 6.1%, respectively). Death was recorded for 24/254 (9.4%) cSSTI and 147/785 (18.7%) cIAI patients. Mortality rates were higher in the group with a baseline APACHE II score of >15 compared with those with a score of ≤ 15 (18.7% versus 3.5% for cSSTI patients and 23.8% versus 16.0% for cIAI patients). A similar trend was seen when cIAI patients were stratified by Sequential Organ Failure Assessment (SOFA) score. CONCLUSIONS The safety and tolerability of tigecycline, alone and in combination, are consistent with the level of critical illness among patients in these real-life studies.

Facetas del politopo de recubrimiento con coeficientes en {0, 1, 2, 3}

ResumenEn dos artículos, publicados en 1989, Balas y Ng dan una metodología para construir facetas del politopo de recubrimiento con coeficientes en {0, 1, 2}. Siguiendo esta metodología, en el presente artículo, decimos cómo se construyen facetas de dicho politopo con coeficientes en {0, 1, 2, 3}.SummaryIn two papers, published in 1989, Balas and Ng give metodology to find facets by covering polytope with coefficients in {0, 1, 2}. We follow this methodology and we say as let formalize facets the covering polytope with coefficients in {0, 1, 2, 3}.