Efficacy of tigecycline for the treatment of complicated skin and soft-tissue infections in real-life clinical practice from five European observational studies.

OBJECTIVES: Tigecycline is an approved treatment for complicated skin and soft-tissue infections (cSSTIs). The efficacy of tigecycline as monotherapy or in combination with other antibacterials in the treatment of cSSTI in routine 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 254 cSSTI patients who received tigecycline were included (mean age 63.2 ± 14.9 years). Of these, 34.4% were in intensive care units, 54.5% acquired their infection in hospital and 90.9% had at least one comorbidity. Infection most commonly affected the limbs (62.4%) and 43.8% of infections were classified as necrotizing. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 15.0 ± 7.9 (n = 205) and 5.8 ± 3.9 (n = 32), respectively, indicating high disease severity. Staphylococcus aureus (52.7%), Escherichia coli (18.0%) and Enterococcus faecium (12.0%) were the most frequently isolated pathogens; 32.9% of infections were polymicrobial and 30.5% were due to resistant pathogens. Overall, 71.8% received tigecycline as monotherapy and 28.2% as combination therapy for a mean duration of 12 days. Clinical response rates at the end of treatment were 79.6% for all patients who received the standard dosage (183/230), 86.7% for patients who received tigecycline as monotherapy (143/165), 75.0% for patients with a nosocomial infection (96/128), 75.3% for patients with an APACHE II score >15 (61/81) and 58.3% for patients with a SOFA score ≥ 7 (7/12). CONCLUSIONS: In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cSSTI with a high severity of illness.

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.

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.

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.

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.

Therapy of 1,025 severely ill patients with complicated infections in a German multicenter study: safety profile and efficacy of tigecycline in different treatment modalities.

This large prospective non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals. Sixty-five percent of the patients had APACHE II scores > 15, indicating high overall disease severity. Complicated intra-abdominal infections (cIAI) or complicated skin and skin tissue infections (cSSTI) were the most common indications, with Staphylococcus aureus, Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens. Clinical success was reported at the end of tigecycline therapy in 74.2% of the total population, in 75.4% of the cIAI and in 82.2% of the cSSTI patients. The subpopulation (28.0% of the patients) infected with multidrug-resistant pathogens (methicillin-resistant S. aureus, extended-spectrum ß-lactamase producers and vancomycin-resistant enterococci) were treated with similar success rates as the overall population. Tigecycline was generally well tolerated. Drug-related adverse events (AEs) were reported in 7.7% of the total population; 2.5% had serious AEs mostly attributable to inefficacy of therapy or deterioration of the disease. Mortality rates were consistent with the types of infection and severity of illness. There was no indication of excessive mortality associated with tigecycline as had been suggested in previously performed meta-analyses. In this large non-interventional study performed in the clinical routine setting, tigecycline achieved favorable clinical success rates in a patient population with high severity of illness and a high prevalence of multidrug-resistant pathogens and showed a good safety and tolerability profile.

Prospective, non-interventional, multi-centre trial of tigecycline in the treatment of severely ill patients with complicated infections: new insights into clinical results and treatment practice.

BACKGROUND: Only few data are available on the efficacy of tigecycline in critically ill patients. METHODS: This prospective, multicenter, non-interventional study investigated the efficacy and safety of tigecycline in hospitalized, severely ill patients with complicated intra-abdominal infections (cIAI) and/or complicated skin and soft tissue infections (cSSTI). Documentation included diagnosis, clinical findings, Acute Physiology and Chronic Health Evaluation II score, laboratory assessments, surgery, clinical outcomes, and adverse events. RESULTS: Six hundred and fifty-six patients (mean Acute Physiology and Chronic Health Evaluation II score 19.1) with cIAI (41%), cSSTI (16%), multiple infection sites (13%) and/or other severe infections (31%) received tigecycline - 51% as monotherapy - due to failure of previous antibiotics (55%) or since resistant pathogens were suspected or proven (45%); clinical cure/improvement rates were 75, 82, 76 and 67% for cIAI, cSSTI, other severe infections and multiple infection sites, respectively. Drug-related adverse events occurred in 6.7% of patients. CONCLUSIONS: The efficacy and safety of tigecycline was demonstrated in a population of severely ill patients with complicated infections.

[Bacteriostatic - bactericidal]. / Bakteriostase - Bakterizidie.

Action of chemotherapeutics on bacteria can be described as "bacteriostatic" or "bactericidal". In vitro, "bactericidal" agents are able to kill >or= 99.9% bacteria of the inoculum within 18-24 h. However, "bactericidal" or "bacteriostatic" effects are dependent on several variables, e.g., inoculum, species, or medium. The number of bacteria found in an infectious process amounts to 10(8)-10(10) CFU/ml (colony-forming units per milliliter) and is far beyond the in vitro test inoculum of 5 x 10(5) CU/ml. Contrary to the term "bactericidal", in vivo a significant number of bacteria will survive. These bacteria are able to regrow, to mutate and to support infection. It is thought that a special advantage of "bactericidal" agents is the rapid killing of bacteria, thus avoiding or at least slowing down development of resistance. Contrary to this assumption, there is now an alarming increase in resistance including third-generation cephalosporins, quinolones and even carbapenems.Recent randomized clinical studies comparing "bacteriostatic" and "bactericidal" regimens revealed an equivalent clinical success. It became obvious that therapy with certain "bacteriostatic" agents even in severe infections is not harmful to patients. In addition, e.g. tetracyclines are able not only to fight bacteria but also to modulate immune response of the host. This property may offer possibilities to develop new strategies in treating infections.

Gingival crevicular fluid levels of calprotectin and myeloperoxidase during therapy for generalized aggressive periodontitis.

BACKGROUND: Levels of the inflammation marker calprotectin in gingival crevicular fluid correspond to clinical and biochemical parameters of periodontal inflammation. Neutrophil granulocytes (polymorphonuclear neutrophils: PMNs) are supposed to be the main source of calprotectin in gingival crevicular fluid, but evidence is still lacking. The influence of periodontal therapy on gingival crevicular fluid levels of calprotectin has not yet been determined. OBJECTIVES: Gingival crevicular fluid levels of calprotectin were monitored during therapy for generalized aggressive periodontitis. Interrelations between calprotectin and the PMN marker myeloperoxidase (MPO) were evaluated. MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from 23 patients with generalized aggressive periodontitis before and 3 months after non-surgical therapy with an adjunctive antimicrobial medication. Clinical parameters were recorded with a pressure-calibrated electronic probe. Levels of calprotectin and MPO in gingival crevicular fluid were analysed by enzyme-linked immunosorbent assay (ELISA) procedures. RESULTS: At baseline, levels of calprotectin and MPO were highly correlated. Bleeding and suppurating sites showed significantly higher levels of calprotectin and MPO than non-bleeding, non-suppurating sites. Therapy significantly decreased levels of both biomarkers. These changes of calprotectin and MPO were highly correlated and also related to probing-depth reduction. Three months after therapy, the levels of both markers still showed significant correlations in initially deep sites, whereas in initially shallow sites no significant correlation was found. After therapy, levels of markers in bleeding and non-bleeding sites were comparable. CONCLUSION: The correlations between calprotectin and MPO indicate that PMNs are a major contributor to the calprotectin content in gingival crevicular fluid of severely affected sites. Calprotectin levels in gingival crevicular fluid and their changes reflect periodontal inflammation as well as the clinical treatment outcome. A prognostic potential of this marker substance remains to be determined.

Antibiotic resistance of urinary pathogens in female general practice patients.

A cross-sectional study was performed to determine the prevalence of antibiotic resistance in women with uncomplicated and complicated lower urinary tract infection (UTI) in Germany. In 36 (of 118 invited) general practices, urine cultures and resistance testing were performed during 4 months on all women presenting with symptoms of UTI. Each patient's symptoms, risk factors and treatment were documented. A total of 445 women were included, and their median age was 53 y. Complicating factors were present in 27% of women. Urine cultures were available for 430 patients. They were sterile in 23%, 53% had 10(5) cfu/ml or more, and 24% had 10(2)-10(4) cfu/ml. E.coli was the most frequent pathogen (68%), followed by Enterococcus faecalis (10%) and Proteus spp. (10%). E.coli resistance levels were 25-40% for amoxicillin, co-amoxiclav, first generation oral cephalosporins, trimethoprim and co-trimoxazole. Nine percent were resistant to fluoroquinolones. E.coli resistance remained low for nitrofurantoin (2%) and third generation oral cephalosporins (3%). Odds for E.coli resistance to most antibiotics were 2-5 times higher in patients with complicating factors, and increased with age. Resistance levels to all common antibiotics were high even in unselected females with UTI in general practices. Older or complicated patients had a significantly higher risk for resistance.

Management of urinary tract infections in female general practice patients.

BACKGROUND: Though guidelines for the management of urinary tract infections (UTI) exist in several European countries, little is known about GPs' adherence, and the appropriateness of their management with regard to antibiotic resistance. OBJECTIVES: To describe German GPs' management of female patients with symptoms of UTI, to assess the diagnostic accuracy of dipsticks in a German general practice setting, to develop diagnostic prediction rules for culture-confirmed UTI, and to compare the adequacy of empirical treatment strategies and GPs' actual prescriptions. METHODS: In 36 (of 118 invited) teaching general practices, urine cultures and resistance testing were performed during 4 months on all symptomatic patients. GPs completed a questionnaire on each patients' symptoms, risk factors and treatment. Adequacy of different treatment approaches was calculated based on culture results. RESULTS: 445 adult women (76% of all patients) were included, with a median age of 53 years. Complicating factors were present in 27%. Urine culture revealed UTI in 77%. GPs' diagnostic accuracy, using both dipsticks and clinical impressions, was low. A positive nitrite test, dysuria and older age were the only predictive factors of culture-confirmed UTI, however the negative predictive value of dipsticks is low (35%). Empirical treatment of all symptomatic patients with either nitrofurantoin or fluoroquinolones would result in a higher rate of appropriate therapies than the individualized approach chosen by the GPs. CONCLUSION: Most patients with urinary symptoms were not treated according to current guidelines, and GPs' diagnostic and therapeutic accuracy was low. Empirical treatment of all symptomatic patients is probably the most effective policy, but implies unnecessary antibiotic prescriptions.