Influence of real-world characteristics on outcomes for patients with methicillin-resistant Staphylococcal skin and soft tissue infections:a multi-country medical chart review in Europe

BACKGROUND: Patient-related (demographic/disease) and treatment-related (drug/clinician/hospital) characteristics were evaluated as potential predictors of healthcare resource use and opportunities for early switch (ES) from intravenous (IV)-to-oral methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotic therapy and early hospital discharge (ED). METHODS: This retrospective observational medical chart study analyzed patients (across 12 European countries) with microbiologically confirmed MRSA complicated skin and soft tissue infections (cSSTI), ≥3 days of IV anti-MRSA antibiotics during hospitalization (July 1, 2010-June 30, 2011), and discharged alive by July 31, 2011. Logistic/linear regression models evaluated characteristics potentially associated with actual resource use (length of IV therapy, length of hospital stay [LOS], IV-to-oral antibiotic switch), and ES and ED (using literature-based and expert-verified criteria) outcomes. RESULTS: 1542 patients (mean ± SD age 60.8 ± 16.5 years; 61.5% males) were assessed with 81.0% hospitalized for MRSA cSSTI as the primary reason. Several patient demographic, infection, complication, treatment, and hospital characteristics were predictive of length of IV therapy, LOS, IV-to-oral antibiotic switch, or ES and ED opportunities. Outcomes and ES and ED opportunities varied across countries. Length of IV therapy and LOS (r = 0.66, p < 0.0001) and eligibilities for ES and ED (r = 0.44, p < 0.0001) showed relatively strong correlations. IV-to-oral antibiotic switch patients had significantly shorter length of IV therapy (−5.19 days, p < 0.001) and non-significantly shorter LOS (−1.86 days, p > 0.05). Certain patient and treatment characteristics were associated with increased odds of ES (healthcare-associated/ hospital-acquired infection) and ED (patient living arrangements, healthcare-associated/ hospital-acquired infection, initiating MRSA-active treatment 1–2 days post cSSTI index date, existing ED protocol), while other factors decreased the odds of ES (no documented MRSA culture, ≥4 days from admission to cSSTI index date, IV-to-oral switch, IV line infection) and ED (dementia, no documented MRSA culture, initiating MRSA-active treatment ≥3 days post cSSTI index date, existing ES protocol). CONCLUSIONS: Practice patterns and opportunity for further ES and ED were affected by several infection, treatment, hospital, and geographical characteristics, which should be considered in identifying ES and ED opportunities and designing interventions for MRSA cSSTI to reduce IV days and LOS while maintaining the quality of care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-476) contains supplementary material, which is available to authorized users

Firsthand Experience and The Subsequent Role of Reflected Knowledge in Cultivating Trust in Global Collaboration

While scholars contend that firsthand experience - time spent onsite observing the people, places, and norms of a distant locale - is crucial in globally distributed collaboration, how such experience actually affects interpersonal dynamics is poorly understood. Based on 47 semistructured interviews and 140 survey responses in a global chemical company, this paper explores the effects of firsthand experience on intersite trust. We find firsthand experience leads not just to direct knowledge of the other, but also knowledge of the self as seen through the eyes of the other - what we call “reflected knowledge”. Reflected and direct knowledge, in turn, affect trust through identification, adaptation, and reduced misunderstandings

Variation in antibiotic treatment for diabetic patients with serious foot infections: A retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Diabetic foot infections are common, serious, and diverse. There is uncertainty about optimal antibiotic treatment, and probably substantial variation in practice. Our aim was to document whether this is the case: A finding that would raise questions about the comparative cost-effectiveness of different regimens and also open the possibility of examining costs and outcomes to determine which should be preferred.</p> <p>Methods</p> <p>We used the Veterans Health Administration (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of hospitalized patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for VA patients with diabetes since 1998, including demographics, ICD-9-CM diagnostic codes, antibiotics prescribed, and VA facility. We identified all patients with ICD-9-CM codes for cellulitis/abscess of the foot and then sub-grouped them according to whether they had cellulitis/abscess plus codes for gangrene, osteomyelitis, skin ulcer, or none of these. For each facility, we determined: 1) The proportion of patients treated with an antibiotic and the initial route of administration; 2) The first antibiotic regimen prescribed for each patient, defined as treatment with the same antibiotic, or combination of antibiotics, for at least 5 continuous days; and 3) The antibacterial spectrum of the first regimen.</p> <p>Results</p> <p>We identified 3,792 patients with cellulitis/abscess of the foot either alone (16.4%), or with ulcer (32.6%), osteomyelitis (19.0%) or gangrene (32.0%). Antibiotics were prescribed for 98.9%. At least 5 continuous days of treatment with an unchanged regimen of one or more antibiotics was prescribed for 59.3%. The means and (ranges) across facilities of the three most common regimens were: 16.4%, (22.8%); 15.7%, (36.1%); and 10.8%, (50.5%). The range of variation across facilities proved substantially greater than that across the different categories of foot infection. We found similar variation in the spectrum of the antibiotic regimen.</p> <p>Conclusions</p> <p>The large variations in regimen appear to reflect differences in facility practice styles rather than case mix. It is unlikely that all regimens are equally cost-effective. Our methods make possible evaluation of many regimens across many facilities, and can be applied in further studies to determine which antibiotic regimens should be preferred.</p

Ertapenem versus piperacillin/tazobactam for the treatment of complicated infections: a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Ertapenem, a new carbapenem with a favorable pharmacokinetic profile, has been approved for the treatment of complicated intra-abdominal Infections (cIAIs), acute pelvic infections (APIs) and complicated skin and skin-structure infections (cSSSIs). The aim of this study is to compare the efficacy and safety of ertapenem with piperacillin/tazobactam, which has been reported to possess good efficacy for the treatment of these complicated infections.</p> <p>Methods</p> <p>We performed a meta-analysis of randomized controlled trials identified in PubMed, Cochrane library and Embase that compared the efficacy and safety of ertapenem with piperacillin/tazobactam for the treatment of complicated infections including cIAIs, APIs, cSSSIs. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure visit. The primary safety outcome was drug related clinical and laboratory adverse events occurred during the treatment and the post-treatment period.</p> <p>Result</p> <p>Six RCTs, involving 3161 patients, were included in our meta-analysis. Ertapenem was associated similar clinical treatment success with piperacillin/tazobactam for complicated infections treatment (clinically evaluable population, 1937 patients, odds ratios: 1.15, 95% confidence intervals: 0.89-1.49; modified intention to treat population, 2855 patients, odds ratios: 1.03, 95% confidence intervals: 0.87-1.22). All of secondary efficacy outcomes analysis obtained similar findings with clinical treatment success. No difference was found about the incidence of drug related adverse events between ertapenem and piperacillin/tazobactam groups.</p> <p>Conclusion</p> <p>This meta-analysis provides evidence that ertapenem 1 g once a day can be used as effectively and safely as recommended dose of piperacillin/tazobactam, for the treatment of complicated infections, particularly of mild to moderate severity. It is an appealing option for the treatment of these complicated infections.</p

Targeting RNA Polymerase Primary σ70 as a Therapeutic Strategy against Methicillin-Resistant Staphylococcus aureus by Antisense Peptide Nucleic Acid

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. METHODOLOGY/PRINCIPAL FINDINGS: By synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM. CONCLUSIONS: The present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections

Activity of the multikinase inhibitor dasatinib against ovarian cancer cells

BackgroundHere, we explore the therapeutic potential of dasatinib, a small-molecule inhibitor that targets multiple cytosolic and membrane-bound tyrosine kinases, including members of the Src kinase family, EphA2, and focal adhesion kinase for the treatment of ovarian cancer.MethodsWe examined the effects of dasatinib on proliferation, invasion, apoptosis, cell-cycle arrest, and kinase activity using a panel of 34 established human ovarian cancer cell lines. Molecular markers for response prediction were studied using gene expression profiling. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions with chemotherapeutic drugs.ResultsConcentration-dependent anti-proliferative effects of dasatinib were seen in all ovarian cancer cell lines tested, but varied significantly between individual cell lines with up to a 3 log-fold difference in the IC(50) values (IC(50) range: 0.001-11.3 micromol l(-1)). Dasatinib significantly inhibited invasion, and induced cell apoptosis, but less cell-cycle arrest. At a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for dasatinib plus carboplatin (mean CI values, range: 0.73-1.11) or paclitaxel (mean CI values, range: 0.76-1.05). In this study, 24 out of 34 (71%) representative ovarian cancer cell lines were highly sensitive to dasatinib, compared with only 8 out of 39 (21%) representative breast cancer cell lines previously reported. Cell lines with high expression of Yes, Lyn, Eph2A, caveolin-1 and 2, moesin, annexin-1, and uPA were particularly sensitive to dasatinib.ConclusionsThese data provide a clear biological rationale to test dasatinib as a single agent or in combination with chemotherapy in patients with ovarian cancer