A Randomized Prospective Study of Cefepime Plus Metronidazole with Imipenem-Cilastatin in the Treatment of Intra-abdominal Infections

Abstract : Background: : Presumptive antimicrobial therapy is an important aspect of the management of intra-abdominal infections. Together with surgery, antimicrobial combinations are still widely used to achieve the required spectrum of activity. The aim of this study was to evaluate the efficacy of parenteral cefepime + metronidazole vs imipenemcilastatin for the treatment of intra-abdominal infections in adult patients. Methods: : Patients with a clinically confirmed diagnosis of intra-abdominal infection were randomized to one of two treatment regimens: cefepime 2 g iv/12 h plus metronidazole 500 mg/8 h or imipenem-cilastatin 500 mg iv/6 h. The primary measure of clinical response was the decline of pre-treatment signs and symptoms of infection. The duration of follow-up was 30 days. Treatment failure was defined as either a lack of improvement or a worsening of pre-treatment signs and symptoms of infection. Surgical management of the infection was determined by the surgeon-in-charge. Results: : Of the 122 intended-to-treat patients included in the study, 60 patients (33 men) were randomized to cefepime + metronidazole and 61 (27 men) to imipenemcilastatin. Cefepime + metronidazole treatment was successful in 52 (87%) patients and imipenem-cilastatin in 44 (72%) patients (p = 0.004). Microbiological eradication was established in similar proportions in both groups (cefepime + metronidazole, 43; imipenem-cilastatin, 38). Conclusion: : Further studies are warranted to confirm the better results with the cefepime + metronidazole regimen for the treatment of intra-abdominal infection

Associations between HIV-RNA-based indicators and virological and clinical outcomes

OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with ≥3viral load (VL) measurements after baseline (the latest of 01/01/2001 or entry into EuroSIDA). Using multivariate Poisson regression we modelled the association between short-term (resistance, triple-class failure) and long-term (all-cause mortality, any AIDS/non-AIDS clinical event) outcomes and the indicators: (i)viraemia copy years (VCY), (ii) Consecutive months with VL ≥50 copies/mL, (iii) percentage of time on ART spent fully suppressed (%FS), (iv) stable on ART, (v)48 weeks snapshot, and (vi) current VL. Indicators were compared using area under the ROC curve (AUC) and different measures of model fit. RESULTS: Adjusted incidence rate ratios for all outcomes tended to increase with increasing VCY, number of consecutive months with VL ≥50 copies/mL, current VL and with lower %FS, but the gradient of increased risk was weak across strata. None of the indicators reliably identified those at risk of long-term outcomes (AUC 0.54-0.58), but performed consistently better with short-term outcomes (triple class failure [AUC 0.67-0.76]) and resistance [AUC 0.64-0.79]). Goodness of fitvariedwith the outcome evaluated, but differences between indicators were small. CONCLUSIONS: Differences between quality of care indicators were small and no indicator performed consistently better than current VL. Given the simplicity in assessing and interpreting this indicator, wepropose to use current VL when HIV-RNA-based indicators are used to evaluate the efficacy of ART programs

Interaction of Water-Soluble CdTe Quantum Dots with Bovine Serum Albumin

Semiconductor nanoparticles (quantum dots) are promising fluorescent markers, but it is very little known about interaction of quantum dots with biological molecules. In this study, interaction of CdTe quantum dots coated with thioglycolic acid (TGA) with bovine serum albumin was investigated. Steady state spectroscopy, atomic force microscopy, electron microscopy and dynamic light scattering methods were used. It was explored how bovine serum albumin affects stability and spectral properties of quantum dots in aqueous media. CdTe–TGA quantum dots in aqueous solution appeared to be not stable and precipitated. Interaction with bovine serum albumin significantly enhanced stability and photoluminescence quantum yield of quantum dots and prevented quantum dots from aggregating

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.Peer reviewe

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens

Objectives: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.Peer reviewe

Secular trends of nocardia infection over 15 years in a tertiary care hospital

Aims: To assess the incidence of nocardia infection over 15 years in a tertiary care hospital. Methods: Over a 15 year period, Nocardia spp were isolated from 20 patients hospitalised at the Geneva University Hospitals, Switzerland. Results: Sixteen patients had one or more underlying conditions. The median time between symptom onset and diagnosis was 30 days. The most common initial unconfirmed diagnosis was pulmonary tuberculosis (four). The lung was involved in 16 cases, followed by the central nervous system (two) and skin (two); one patient had disseminated infection. The most common species identified was N asteroides. In vitro susceptibility testing was performed on 14 of 20 strains. All strains were susceptible to imipenem and amikacin. Initial treatment with trimethoprim/sulfamethoxazole (TMP/SMX) was started in 14 patients, although five patients had to be switched to another treatment because of side effects or lack of efficacy. A cure was observed in 15 patients, death in three, and relapse or complications in two. Conclusions: Nocardiosis can become a severe infection and mainly affects profoundly immunocompromised patients. Differential diagnosis often delays the time to diagnosis, which worsens the outcome. New diagnostic tools, such as the polymerase chain reaction, could provide more rapid and reliable results. TMT/SMX was the most commonly prescribed treatment, but needed to be changed for another treatment because of side effects or lack of efficacy in a considerable proportion of patients. Imipenem should be used as an alternative treatment for severely ill patients, and the sulfa combination for less severe infections