Ceftaroline Fosamil Therapy in Patients With Acute Bacterial Skin and Skin Structure Infections With Systemic Inflammatory Signs: A Retrospective Dose Comparison Across Three Pivotal Trials.

BACKGROUND: Post-hoc analysis compared pharmacokinetics and clinical outcomes of ceftaroline fosamil 600 mg every 12 (q12h) versus every 8 hours (q8h), in patients with acute bacterial skin and skin structure infections (ABSSSI) and signs of sepsis. METHODS: Clinical outcomes at test-of-cure in patients with ABSSSI and systemic inflammatory signs/systemic inflammatory response (SIRS), and ceftaroline minimum inhibitory concentrations (MICs) against baseline pathogens were compared between COVERS (ceftaroline fosamil 600 mg q8h, 2-h infusion) and the CANVAS 1 and 2 trials (ceftaroline fosamil 600 mg q12h, 1-h infusion). Ceftaroline exposures among patients in COVERS with or without markers of sepsis were compared using population pharmacokinetic (PK) modeling. RESULTS: In COVERS, 62% (312/506) and 41% (208/506) of ceftaroline fosamil-treated patients had ≥1 systemic sign or SIRS, respectively and 55% (378/693) and 22% (152/693), respectively in the CANVAS trials. Clinical cure rates for the modified intent-to-treat (MITT) population in COVERS and CANVAS were similar for ceftaroline fosamil-treated patients with ≥1 sign of sepsis (82% [255/312] and 85% [335/394]) and for those with SIRS (84% [168/199] and 85% [131/155]). Ceftaroline MIC distributions were similar across trials. Sepsis did not affect predicted individual steady-state ceftaroline exposures. CONCLUSIONS: Clinical cure rates in patients with ≥1 systemic inflammatory sign or SIRS were comparable for both ceftaroline fosamil dosage regimens. Pathogen susceptibilities to ceftaroline were similar across trials. Ceftaroline exposures were not affected by disease severity. Ceftaroline fosamil 600 mg q12h is a robust dosage regimen for most ABSSSI patients with sepsis

Early response to antibiotic treatment in European patients hospitalized with complicated skin and soft tissue infections: analysis of the REACH study

Background: The treatment of complicated skin and soft tissue infections (cSSTI) is challenging and many patients do not receive adequate first-line therapy. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe cSSTI or Community-Acquired Pneumonia in the Hospital Setting) was a retrospective observational study of cSSTI patients in real-life settings in European hospitals. In this analysis, we review characteristics and outcomes of patients with an early response (<= 72 hours) compared with those without an early response to treatment. We also compare the results according to two differing definitions of early response, one of which (Definition 1) requires resolution of fever within 72 hours, in line with previous US FDA guidelines. Methods: Patients were adults hospitalized with cSSTIs 2010-2011 and requiring treatment with intravenous antibiotics. Clinical management, clinical outcomes and healthcare resource use were assessed using a descriptive analysis approach. Results: The analysis set included 600 patients, of which 363 showed early response with Definition 1 and 417 with Definition 2. Initial treatment modification was frequent, and highest in patients without early response (48.1% with Definition 1). Patients without early response were more likely to have diabetes than those with early response (31.6% vs. 22.9%,respectively) and to suffer from more severe disease (e.g. skin necrosis: 14.8% and 7.7%,respectively), to be infected with difficult-to-treat microorganisms and to have recurrent infections. Furthermore, patients without early response had a higher rate of adverse clinical outcomes (e.g. septic shock) and higher use of healthcare resources. The results obtained with the two definitions for early response were largely similar. Conclusions: This study highlights the significance of early evaluation of patients in hospitals, in potentially preventing prolonged use of inappropriate or ineffective antibacterial therapy

Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda

Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7-6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7-9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0-2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8-5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).HHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda

Seroprevalence and factors associated with herpes simplex virus type 2 among HIV-negative high-risk men who have sex with men from Rio de Janeiro, Brazil: a cross-sectional study

Submitted by Frederico Azevedo ([email protected]) on 2010-11-04T17:19:23Z No. of bitstreams: 1 seroprevalence_and_factors.pdf: 273577 bytes, checksum: 742e51b14ff9ef765bf31b52f3fc8f1a (MD5)Made available in DSpace on 2010-11-04T17:19:23Z (GMT). No. of bitstreams: 1 seroprevalence_and_factors.pdf: 273577 bytes, checksum: 742e51b14ff9ef765bf31b52f3fc8f1a (MD5) Previous issue date: 2009Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Comunicação e Informação Científica e Tecnológica em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Background: Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcer disease in developing countries, including Brazil, and is especially prevalent among men who have sex with men (MSM). HSV-2 infection represents a risk factor for the acquisition and transmission of other sexually transmitted diseases. The goal of the present cross-sectional study was to estimate HSV- 2 seroprevalence and to determine the factors associated with HSV-2 seropositivity in HIVnegative high-risk MSM from Rio de Janeiro, Brazil. Methods: Stored sera were tested to estimate HSV-2 seroprevalence, while socio-demographic and sexual behavior data were used to measure associations between risk factors and HSV-2 seropositivity. Using the Poisson regression model with robust variance, prevalence ratios (PR) were used to estimate de degree of association between risk factors and HSV-2 seropositivity in bivariate and multivariate analyses. Results: Seroprevalence of HSV-2 was of 45.7% (184 out of 403). Factors independently associated with HSV-2 seroprevalence in the multivariate model were: older age (≥ 26 years, PR: 1.41 95% Confidence Interval: 1.11–1.78), non-white race (PR: 1.32 95%CI: 1.06–1.64), positive serology for syphilis (PR: 1.65 95%CI: 1.33–2.05), positive serology for hepatitis B (PR: 1.25 95%CI: 0.99–1.57), stable male partner in the past 6 months (PR: 1.42 95%CI: 1.12–1.79), and unprotected anal sex with a stable female partner (PR: 1.46 95%CI: 1.05–2.04) in the 6 months preceding the crosssectional assessment. Conclusion: The present study made evident a high prevalence of HSV-2 infection in a sample of HIV-negative high-risk MSM from Rio de Janeiro. This finding indicates the need and urgency for implementing integrated programs for the prevention of HSV-2 and other sexually transmitted diseases, and, in particular, programs targeting high-risk MSM