Streptococcal and enterococcal endocarditis: time for individualized antibiotherapy?

Recommendations for the treatment of streptococcal and enterococcal endocarditis are based on old efficacy studies, but the starting doses have never been reassessed and are associated with significant adverse events. Based on data from other serious infections, we suggest that maintaining a concentration of ß-lactams higher than 4-6 times the responsible bacteria MIC 100% of the time in the heart of the vegetation would be a pertinent therapeutic objective. The data point to a diffusion gradient of ß-lactams in the vegetation. Yet, so far as is known, the ratio of antibiotic concentration at steady state between plasma and vegetation cannot be completely determined. Answering this crucial question would make it possible for each patient to have a targeted ß-lactam plasma concentration, according to the MIC for the responsible bacteria. This would lead the way to personalized antibiotherapy and allow a safe switch to oral medication.

Ventilator-Associated Pneumonia in COVID-19 Patients: A Retrospective Cohort Study.

INTRODUCTION: Aim of this study is to analyse the characteristics of ventilator-associated pneumonia (VAP) inpatients infected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: A retrospective study was conducted, including coronavirus infectious disease 2019 (COVID-19) patients who developed VAP from March to May 2020 (VAP COVID-19). They were compared to non-COVID-19 patients who developed VAP from January 2011 to December 2019 (VAP NO COVID-19) and COVID-19 patients who did not develop VAP (NO VAP COVID-19). RESULTS: Overall, 42 patients were included in the VAP COVID-19group, 37 in the NO VAP COVID-19 group, and 188 in the VAP NO COVID-19 group. VAP COVID-19 had significantly higher rates of shock (71% vs. 48%, p = 0.009), death in ICU (52% vs. 30%, p = 0.011), VAP recurrence (28% vs. 4%, p < 0.0001), positive blood culture (26% vs. 13%, p = 0.038), and polymicrobial culture (28% vs. 13%, p = 0.011) than VAP NO COVID-19. At the multivariate analysis, death in patients with VAP was associated with shock (p = 0.032) and SARS-CoV-2 (p = 0.008) infection. CONCLUSIONS: VAP in COVID-19 patients is associated with shock, bloodstream, and polymicrobial infections.

Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin.

In 2017, five cases of severe haemorrhages during treatment with cefazolin occurred in France. The aim of this study was to assess the risk of haemorrhage related to treatment with cefazolin by evaluating haemostatic parameters and bleeding events. A retrospective study was conducted from January 2016 to December 2017. Two populations were analysed: (i) overall population, which included all patients treated with cefazolin during this period and (ii) coagulation study population, which included all patients treated with cefazolin with available coagulation parameters (activated partial thromboplastin time (aPTT) and international normalised ratio (INR) at baseline and at the end of treatment or EoT). Values of either aPTT or INR at baseline and at EoT were compared. Cases of severe haemorrhages were reported and correlated with values of aPTT and INR. Overall, 132 patients received cefazolin and 59/132 (45%) were included in the coagulation study group. A significant increase of median aPTT was observed from baseline to EoT (39.5 and 44.3 sec; p = 0.004, respectively). Overall, severe haemorrhage occurred in 7/132 (5%) patients. Coagulation parameters were available in three of them, and no correlation was observed between bleeding events and aPTT increase. This study showed that bleeding is probably more frequent than ever reported before during cefazolin treatment. The significant increase of aPTT observed during cefazolin treatment was not correlated with risk of haemorrhage. Further studies are needed to explore the possible physio-pathological pathways behind the modification of haemostatic parameters and risk of haemorrhage.

Comparative analysis of methods for real-time analytical control of chemotherapies preparations.

Control of chemotherapies preparations are now an obligation in France, though analytical control is compulsory. Several methods are available and none of them is presumed as ideal. We wanted to compare them so as to determine which one could be the best choice. We compared non analytical (visual and video-assisted, gravimetric) and analytical (HPLC/FIA, UV/FT-IR, UV/Raman, Raman) methods thanks to our experience and a SWOT analysis. The results of the analysis show great differences between the techniques, but as expected none us them is without defects. However they can probably be used in synergy. Overall for the pharmacist willing to get involved, the implementation of the control for chemotherapies preparations must be widely anticipated, with the listing of every parameter, and remains according to us an analyst's job.

Erythrocyte and plasma ribavirin concentrations in the assessment of early and sustained virological responses to pegylated interferon-alpha 2a and ribavirin in patients coinfected with hepatitis C virus and HIV.

OBJECTIVES: To determine the relationship between erythrocyte and plasma ribavirin concentrations in hepatitis C virus (HCV)/HIV-coinfected patients, and to correlate ribavirin exposure with early and sustained virological response (EVR and SVR) and haemoglobin level reductions. METHODS: Clinical and biological data from 68 HCV/HIV-coinfected patients were recorded at baseline, week 4 (W4), week 12 and at 24 weeks after completion of treatment. Plasma and erythrocyte ribavirin concentrations were determined 12 h after the final ribavirin dose (C(min)). RESULTS: Erythrocyte ribavirin concentrations were 100-fold higher than plasma concentrations, with a significant relationship between them (P < 0.05). In patients with HCV genotype 1 or 4, a plasma ribavirin C(min) threshold of 1.95 mg/L at W4 tended to predict EVR [sensitivity 44%; specificity 87%; AUC 0.67 (95% CI 0.50-0.84)] and was predictive of SVR [sensitivity 58%; specificity 84%; AUC 0.71 (95% CI 0.51-0.90)]. Among patients with these HCV genotypes, an erythrocyte ribavirin C(min) threshold of 146 mg/L at W4 was found to be the best value for discriminating between responders and non-responders for both EVR [sensitivity 67%; specificity 75%; AUC 0.58 (95% CI 0.24-0.93)] and SVR [sensitivity 50%; specificity 80%; AUC 0.70 (95% CI 0.39-1.01)]. We also demonstrated a significant relationship between reduced haemoglobin levels and plasma ribavirin C(min) at W4 (P = 0.05). CONCLUSIONS: Therapeutic drug monitoring may be useful for the management of anti-HCV treatment in HCV/HIV-coinfected patients.