COVID-19 early curative treatments in kidney transplant recipients: is it really reasonable at the Omicron era?

Objective: Data about efficacy and safety of the latest COVID-19 treatments as nirmatrelvir/ritonavir (n/r) or Sotrovimab is scarce in solid organ transplant recipients in the Omicron era. This study aims at describing the outcome of kidney transplant recipients (KTRs) presenting Omicron infection according to their management: n/r, sotrovimab or no specific treatment. Patients and methods: We conducted a monocentric, retrospective observational study, including KTRs diagnosed Omicron infection between January and May 1st 2022 and compared their outcome (primary outcome defined as hospital admission for COVID-19 within a month after symptoms onset) according to early COVID-19 management. Results: Forty-five patients were included: 22 treated (12 n/r, 10 sotrovimab) and 23 with no specific treatment. The groups were statistically comparable. Two patients were admitted for COVID-19: one in each group, resulting in a non-different probability of the primary outcome at on month (p=0.9). Three patients presented tacrolimus overdose including two with acute kidney injury. Conclusions: There was no difference in outcome according to early therapeutic management: n/r, sotrovimab or no specific treatment. Our study both underlines a decreased severity of Omicron COVID-19 in KTRs (probably related to vaccinal immunity and decreased virulence of Omicron) and a potential severe adverse effects with n/r.

Objectif: Les données sur l'efficacité et la sécurité des derniers traitements de la Covid-19 sont peu nombreuses à l'ère du variant Omicron. Cette étude avait pour objectif de décrire l'évolution des transplantés rénaux (TR) présentant une infection à Omicron selon le traitement précoce reçu : nirmatrelvir/ritonavir (n/r), sotrovimab, ou pas de traitement. Patients et méthodes: Il s'agissait d'une étude monocentrique rétrospective observationnelle incluant tous les TR présentant une infection confirmée à Omicron entre le 1er janvier 2022 et le 1er mai 2022 et comparant leur évolution (critère de jugement principal : admission hospitalière pour Covid-19 à un mois du début des symptômes) selon leur prise en charge. Résultats: Quarante-cinq patients ont été inclus : 22 traités (12 n/r et 10 sotrovimab) et 23 non traités. Les groupes étaient statistiquement comparables. Seulement deux patients ont présenté le critère de jugement principal : un n/r et un non traité, avec une probabilité à un mois non différente (p = 0,9). Trois patients sur 12 ont en revanche présenté des surdosages en tacrolimus dans le groupe n/r, dont deux avec une insuffisance rénale aiguë. Conclusions: Dans les limites d'un petit effectif, nous n'avons pas montré de bénéfice au traitement précoce par n/r ou sotrovimab. On peut évoquer un effet de l'immunité vaccinale et une baisse de virulence du SARS-CoV-2. En revanche, les effets secondaires du n/r ne sont pas anodins avec des surdosages sévères malgré des protocoles de service précis. La balance bénéfice-risque de ces traitements doit être rediscutée.

Impact of clinical pharmacist interventions in a bone and joint infection orthoseptic surgery unit.

OBJECTIVES: To assess the impact of interventions of a clinical pharmacist in a unit of orthopedic surgery specialized in bone and joint infections. METHODS: Daily, in routine, a clinical pharmacist analyzed medication prescribed to inpatients via a computerized physician order entry (CPOE) (Phedra software). His attention was particularly focused on the impact of antibiotics on other medications. For this study, all of the pharmacist interventions (PI) have been retrospectively collected, then anonymized, and assessed over a two-month period. RESULTS: Thirty-eight patients were hospitalized during the study period, with a mean age of 63 years old. Forty-five interventions were identified which represents a mean of 1.18 pharmaceutical interventions per patient. Most of them concerned lack of follow-up (24%) and drug-drug interactions (22%) and widely non-anti-infectious medication (35 interventions) with levothyroxine (10 interventions) as the most involved non-anti-infectious molecule. Among antibiotics, with respectively 9 and 8 interventions, rifampicin and fluoroquinolones (6 interventions for moxifloxacin) were the most concerned notably for drug-drug interactions with usual treatment. CONCLUSION: In this observational retrospective study, 1.18 pharmacist interventions (PI) per patient were observed. Most of them are lack of follow-up and drug-drug interactions especially with usual treatment of patients. Moxifloxacin and rifampicin were the most antibiotics involved. Patients' characteristics (older, polypharmacy), long-term hospitalization and surgery are known to be predictive factors of medication errors and this study highlights the importance of the presence of clinical pharmacist in orthopedic surgery wards.

Pharmacokinetics/pharmacodynamics of ceftobiprole in patients on extracorporeal membrane oxygenation.

INTRODUCTION: Due to its bacteriological spectrum and efficacy in skin and soft tissue infections, ceftobiprole may be of interest for extracorporeal membrane oxygenation (ECMO) cannula-related infection. It is unknown whether ceftobiprole pharmacokinetics (PK) are changed by ECMO. METHODS: A retrospective monocentric cohort study was performed of 35 patients with suspected ECMO-related cannula infections (28 on ECMO, seven after ECMO removal), who received ceftobiprole as empiric treatment and had ceftobiprole blood levels measured at trough, peak and CT50 (50% of the dosing interval). Ceftobiprole blood levels of the 28 patients on ECMO were compared with those of the seven patients without ECMO. Factors associated with low ceftobiprole trough levels were also explored. RESULTS: Among the 35 patients included, 29 had a confirmed cannula-related infection and 48 pathogens were isolated. Ceftobiprole MIC was determined in 29 of these 48, and 23 (79%) were susceptible to ceftobiprole. Ceftobiprole blood levels (at trough, peak and CT50) were similar in ECMO and non-ECMO patients. Moreover, in patients whose pathogens responsible for infection were susceptible to ceftobiprole, 94% had a ceftobiprole trough level above the MIC. Ceftobiprole blood levels were decreased in patients with acute renal failure requiring renal replacement therapy (RRT) and in those with increased renal clearance (defined as creatinine clearance > 130 mL/min), independent of ECMO. No other factor was associated with modification of ceftobiprole PK/pharmacodynamics (PK/PD). CONCLUSIONS: The ceftobiprole PK/PD was no different in patients during ECMO or after its withdrawal. Factors associated with decreased ceftobiprole blood levels were patients requiring RRT and those with increased renal clearance.

Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.

Background: Temocillin is a ß-lactam that is not hydrolysed by ESBLs. Objectives: To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Methods: Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Results: Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ±â€Š15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6). Conclusions: The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.

Total and Unbound Pharmacokinetics of Cefiderocol in Critically Ill Patients.

BACKGROUND: Cefiderocol is a siderophore cephalosporin antibiotic active against Gram-negative bacteria, including extended-spectrum beta-lactamase and carbapenemase-producing strains. The pharmacokinetics of cefiderocol has been studied in healthy subjects and particularly in phase II and III studies. This retrospective study investigated intravenous cefiderocol population pharmacokinetics in adult patients treated by cefiderocol. METHODS: We studied 55 consecutive patients hospitalized in an intensive care unit. Cefiderocol plasma samples were obtained on different occasions during treatment. Plasma concentration was assayed using mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2020R1. RESULTS: A total of 205 plasma samples were obtained from 55 patients. Eighty percent of patients received cefiderocol for ventilator-associated pneumonia due to carbapenem-resistant Pseudomonas aeruginosa infection. Cefiderocol concentration time-courses were best fit to a two-compartment open model with first-order elimination. Elimination clearance was positively related to renal function (estimated by the CKD formula). Adding albumin plasma binding in the model significantly improved the model assuming a ~40% unbound drug fraction given a ~40 g/L albuminemia. The final model included CKD plus cefiderocol plasma binding effects. Fat-free mass was better than total body weight to influence, via the allometric rule, clearance and volume terms, but this effect was negligible. The final clearance based on free circulating drug (CLU) for a typical patient, CKD = 90, was 7.38 L/h [relative standard error, RSE, 22%] with a between-subject variability of 0.47 [RSE 10%] (exponential distribution). CONCLUSION: This study showed that albumin binding and CKD effects were significant predictors of unbound and total plasma cefiderocol concentrations. Our results indicate that individual adjustment of cefiderocol can be used to reach high minimum inhibitory concentrations based on an estimation of unbound drug concentration and optimize therapeutic efficacy.

Antibiotic Stewardship in Treatment of Osteoarticular Infections Based on Local Epidemiology and Bacterial Growth Times.

Incubation for 14 days is recommended for the culture of microorganisms from osteoarticular infections (OAI), but there are no recommendations for postoperative antibiotic stewardship concerning empirical antimicrobial therapy (EAT), while prolonging broad-spectrum EAT results in adverse effects. The aim of this study was to describe the local OAI epidemiology with consideration of bacterial growth times to determine which antibiotic stewardship intervention should be implemented in cases of negative culture after 2 days of incubation. We performed a 1-year, single-center, noninterventional cohort study at the Pitié-Salpêtrière hospital OAI reference center. Samples were taken as part of the local standard of care protocol for adult patients who underwent surgery for OAI (native or device related) and received EAT (i.e., piperacillin-tazobactam plus daptomycin [PTD]) following surgery. The time to culture positivity was monitored daily. Overall, 147 patients were recruited, accounting for 151 episodes of OAI, including 112 device-related infections. Microbiological cultures were positive in 144 cases, including 42% polymicrobial infections. Overall, a definitive microbiological result was obtained within 48 h in 118 cases (78%) and within 5 days in 130 cases (86%). After 5 days, only Gram-positive bacteria were recovered, especially Cutibacterium acnes, Staphylococcus spp., and Streptococcus spp. Overall, 90% of culture-positive OAI were correctly treated with the locally established EAT. EAT guidance for OAI was in agreement with our local epidemiology. Our results supported antibiotic stewardship intervention consisting of stopping piperacillin-tazobactam treatment at day 5 in cases of negative culture. IMPORTANCE Osteoarticular infections (OAI) remain challenging to diagnose and to treat. One of the issues concerns postoperative empirical antimicrobial therapy (EAT), which is usually a combination of broad-spectrum antibiotics. This EAT is maintained up to 2 weeks, until the availability of the microbiological results (identification and drug susceptibility testing of the microorganisms responsible for the OAI). Our results provide new data that will help to improve OAI management, especially EAT. Indeed, we have shown that antibiotic stewardship intervention consisting of stopping the antibiotic targeting Gram-negative bacteria included in the EAT could be implemented in cases where culture is negative after 5 days of incubation. The benefits of such an antibiotic stewardship plan include improved patient outcomes, reduced adverse events (including Clostridioides difficile infection), improvement in rates of susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care.

Spike Gene Evolution and Immune Escape Mutations in Patients with Mild or Moderate Forms of COVID-19 and Treated with Monoclonal Antibodies Therapies.

We explored the molecular evolution of the spike gene after the administration of anti-spike monoclonal antibodies in patients with mild or moderate forms of COVID-19. Four out of the 13 patients acquired a mutation during follow-up; two mutations (G1204E and E406G) appeared as a mixture without clinical impact, while the Q493R mutation emerged in two patients (one receiving bamlanivimab and one receiving bamlanivimab/etesevimab) with fatal outcomes. Careful virological monitoring of patients treated with mAbs should be performed, especially in immunosuppressed patients.

Dual beta-lactam treatment: Pros and cons.

The battle against microscopic pathogens has always baffled the scientific community. Nowadays, multidrug-resistant microorganisms lead to high in-hospital mortality, increased hospital stays, and high health-related costs. Treating infections due to these high-resistance pathogens with a low number of antibiotic molecules creates the need for new strategies. Although some already think of a "postantibiotic era" with bacteriophages as the main futuristic weapon in antibacterial armament, others rethink the usage of the already existent drugs. Dual beta-lactam therapy has been used for quite some time as an empirical therapy for some severe infections such as endocarditis or meningitis. However, studies regarding the use of a beta-lactam combination stopped being made a long time ago, and it seems the scientific community has no interest in evaluating this as a treatment option. Could this strategy be applied to treat infections due to multidrug-resistant bacteria? Could this be the answer while waiting for the "postantibiotic era"? What kind of pathogens could we fight using dual beta-lactams? What are the downsides of this strategy? These are some of the questions the authors try to answer in this review. In addition, we try to convince our peers to turn once more into researching beta-lactam combinations and exploring its potential benefits.

Surging bloodstream infections and antimicrobial resistance during the first wave of COVID-19: a study in a large multihospital institution in the Paris region.

OBJECTIVES: This study measured the impact of the first wave of COVID-19 pandemic (COVID-19) (March-April 2020) on the incidence of bloodstream infections (BSIs) at Assistance Publique - Hôpitaux de Paris (APHP), the largest multisite public healthcare institution in France. METHODS: The number of patient admission blood cultures (BCs) collected, number of positive BCs, and antibiotic resistance and consumption were analysed retrospectively for the first quarter of 2020, and also for the first quarter of 2019 for comparison, in 25 APHP hospitals (ca. 14 000 beds). RESULTS: Up to a fourth of patients admitted in March-April 2020 in these hospitals had COVID-19. The BSI rate per 100 admissions increased overall by 24% in March 2020 and 115% in April 2020, and separately for the major pathogens (Escherichia coli, Klebsiella pneumoniae, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, yeasts). A sharp increase in the rate of BSIs caused by microorganisms resistant to third-generation cephalosporins (3GC) was also observed in March-April 2020, particularly in K. pneumoniae, enterobacterial species naturally producing inducible AmpC (Enterobacter cloacae...), and P. aeruginosa. A concomitant increase in 3GC consumption occurred. CONCLUSIONS: The COVID-19 pandemic had a strong impact on hospital management and also unfavourable effects on severe infections, antimicrobial resistance, and laboratory work diagnostics.

Simple and accurate quantitative analysis of cefiderocol and ceftobiprole in human plasma using liquid chromatography-isotope dilution tandem mass spectrometry: interest for their therapeutic drug monitoring and pharmacokinetic studies.

OBJECTIVES: Cefiderocol and ceftobiprole are new generation cephalosporin antibiotics that exhibit high inter-individual plasma concentration variability that potentially impact their efficacy or toxicity. The aim of this study was to develop and validate a selective, simple, and fast UPLC-MS/MS method for simultaneous quantification of cefiderocol and ceftobiprole in human plasma to enable their therapeutic drug monitoring (TDM) and support PK and PK/PD studies, in particular in critically ill patients. METHODS: After a simple and fast single-step protein precipitation, cefiderocol and ceftobiprole were separated on a Waters Acquity UPLC BEH C18 column by linear gradient elution; with subsequent detection by Shimadzu MS 8060 triple quadrupole tandem mass spectrometer in a positive ionization mode. RESULTS: Analysis time was 5 min per run. The analytical performance of the method in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect (ME), extraction recovery (ER), limit of quantification, dilution integrity, and stability of analytes under different conditions met all criteria for a bioanalytical method for the quantification of drugs. The calibration curves were linear over the range of 1-200 mg/L for cefiderocol and 0.5-100 mg/L for ceftobiprole with a linear regression coefficient above 0.995 for both. CONCLUSIONS: A simple, fast, and selective liquid chroma-tography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of cefiderocol and ceftobiprole. This new method was successfully applied to the measurement of plasma concentration of cefiderocol and ceftobiprole in critically ill patients and showed good performance for their therapeutic monitoring and optimizing antibiotic therapy.

Susceptibility Testing Is Key for the Success of Cefiderocol Treatment: A Retrospective Cohort Study.

Cefiderocol is a novel siderophore cephalosporin, which has proven in vitro activity against carbapenem-resistant (CR) Gram-negative pathogens and stability towards all carbapenemases. The aim of this study was to describe the first cases of prescriptions and the efficacy of cefiderocol for compassionate use in the 2 months following its access in France. We performed a national retrospective study of all patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. We collected clinical characteristics and outcome through a standard questionnaire. Bacterial isolates from 12 patients were centralized and analyzed in the French National Reference Center for Antimicrobial Resistance, and sequenced using Illumina technology. Finally, 13 patients from 7 French university hospitals were included in the study. The main type of infection treated by cefiderocol was respiratory tract infections (RTI, n = 10). The targeted bacteria were Pseudomonas aeruginosa (n = 12), including carbapenemase-producing P. aeruginosa (n = 9), Acinetobacter baumannii (n = 2), Klebsiella pneumoniae (n = 1), and Enterobacter hormaechei (n = 1). Overall, of the 12 patients whose samples were analyzed, 5 P. aeruginosa strains were not susceptible to cefiderocol (4 categorized as resistant and 1 as intermediate) according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. If considering susceptible strains, the cure rate was 6/7, while being 0/5 among not-susceptible strains. This study underlines the necessity to test strains in adequate conditions.

Antiretroviral drug reduction in highly experienced HIV-infected patients receiving a multidrug regimen: the ECOVIR study.

OBJECTIVES: In a context of life-long therapy, we asked whether it could be possible to reduce the number of antiretroviral drugs without jeopardizing viral suppression. METHODS: ECOVIR was a prospective study aiming to assess whether in patients on combination ART with ≥4 antiretrovirals for ≥24 weeks and virally suppressed for ≥48 weeks, a drug-reduced (DR) regimen could be proposed. The intervention consisted of discontinuing genotypically less susceptible drugs to reach a DR regimen with ≤3 antiretrovirals. The primary endpoint was the proportion of patients maintaining viral suppression at week (W) 24. RESULTS: From 89 eligible individuals for the study, a DR regimen was proposed in 86 (97%) patients, of whom 71 were switched to a DR regimen. Baseline characteristics [median (IQR)] were: age 58 (53-65) years, duration of treatment 24 (21-26) years and viral suppression 8 (6-11) years. The cumulative resistance profile showed full resistance to lamivudine/emtricitabine (91%), abacavir (74%), efavirenz/nevirapine (70%), rilpivirine (56%), darunavir (q24h/q12h) (42%/29%), lopinavir (69%), atazanavir (71%) and raltegravir (24%). The final DR regimen consisted of a two-drug or three-drug regimen in 54 patients (76%) and in 17 patients (24%), respectively. The success rate of a DR regimen at W24 was 93.9% (95% CI 84.4-97.6, Kaplan-Meier estimate). Four patients experienced virological failure (at W4, W8 and W12), all with plasma viral load (pVL) <600 copies/mL and no emergence of resistance mutations. The DR strategy allowed a monthly cost saving of 36%. CONCLUSIONS: In experienced patients with high-level resistance, individualized strategies based on expert advice can offer DR regimen options with fewer drug-drug interactions and a significant economic impact while ensuring virological success.

Infliximab biosimilar for treating neurosarcoidosis: tolerance and efficacy in a retrospective study including switch from the originator and initiation of treatment.

OBJECTIVES: Infliximab is increasingly used to treat neurosarcoidosis. We aimed to determine the efficacy and tolerance of an infliximab biosimilar for treating neurosarcoidosis. METHODS: We conducted a retrospective single-center study to describe the efficacy, safety and immunogenicity of an infliximab biosimilar in neurosarcoidosis patients. We compared the survival time without relapse while receiving the biosimilar or previous originator-infliximab treatment. RESULTS: Twenty patients with histologically documented neurosarcoidosis were treated with an infliximab biosimilar (initiation of treatment in 12 and switch from the originator drug in 8) between February 2016 and August 2018. All patients presenting with neurological involvement of one or more areas, including meningeal (n = 15), cerebral (n = 10), spinal cord (n = 9), and/or cranial nerves (n = 5); epilepsy (n = 3); and/or intracranial hypertension (n = 3) were enrolled. Eighteen patients received glucocorticoids during infliximab treatment, and 16 had methotrexate or azathioprine concomitant treatment. The median duration of follow-up was 25 months (19-28). Six patients relapsed during biosimilar treatment. Relapse rates and time-to-relapse did not differ between the infliximab originator previously received and biosimilar treatment groups (p = 0.40 and 0.51, respectively). Nine patients experienced 11 adverse events with the infliximab biosimilar, including infections (n = 5), urticaria (n = 4), headache (n = 1), and diarrhea (n = 1). All side effects were grade 2 or less using the WHO classification. CONCLUSIONS: In this retrospective study, the infliximab biosimilar was efficacious and safe for treating neurosarcoidosis.

Use of non-carbapenem antibiotics to treat severe extended-spectrum ß-lactamase-producing Enterobacteriaceae infections in intensive care unit patients.

OBJECTIVES: The aim of this study was to evaluate the use of non-carbapenem antibiotics to treat severe extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) infections in intensive care unit (ICU) patients. METHODS: This retrospective observational study conducted in two ICUs compared the outcomes of patients with ESBL-E infections administered a carbapenem or a non-carbapenem antibiotic as their definitive treatment. The primary outcome was treatment failure within 30 days, a composite endpoint of ESBL-E infection recurrence and 30-day mortality. Secondary outcomes included 30-day and in-hospital mortality rates, ESBL-E infection recurrence and infection(s) due to other pathogen(s). RESULTS: Among 107 patients included in the study, 67 received a carbapenem and 40 received a non-carbapenem antibiotic as their definitive treatment. Clinical characteristics of the two groups were similar. Comparing patients given a non-carbapenem antibiotic with those administered a carbapenem, they had similar 30-day treatment failure (43% vs. 61%, respectively; P = 0.06) and ESBL-E infection recurrence rates (25% vs. 22%; P = 0.8), but the former had lower 30-day mortality (23% vs. 45%; P = 0.02) and in-hospital mortality rates (23% vs. 49%; P = 0.005). Secondary infection rates caused by other pathogen(s), including Clostridium difficile, were comparable. Outcomes were comparable regardless of whether or not patients received an empirical carbapenem. CONCLUSION: For ICU patients with severe ESBL-E infections, treatment with a non-carbapenem antibiotic was not associated with poorer outcomes compared with a carbapenem antibiotic.

Treating hepatic encephalopathy in cirrhotic patients admitted to ICU with sodium phenylbutyrate: a preliminary study.

Hepatic encephalopathy (HE) influences short-term and long-term prognoses. Recently, glycerol phenylbutyrate (PB), that lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion, has shown that it was effective in preventing the occurrence of HE in RCT. The aim was to assess the benefits of sodium PB in cirrhotic patients admitted to ICU for overt HE, in terms of ammonia levels decrease, neurological improvement, and survival. Cirrhotic patients who presented with overt HE, ammonia levels >100 µmol/L, and did not display any contra-indication were included. Sodium PB was administered at 200 mg/kg/day. Control group included historical controls treated by standard therapy, matched for age, sex, MELD score, and severity of HE. Eighteen patients were included and treated with sodium PB (age: 59 [45-68], male gender: 15 [83%], Child-Pugh B: 8 [44%], Child-Pugh C: 10 [56%], and MELD score: 16 [13-23]). Ammonia levels significantly decreased in the PB as compared to the control group from inclusion to 12 h and from inclusion to 48 h (P = 0.0201 and P = 0.0230, respectively). The proportion of patients displaying neurological improvement was only higher in the PB-treated group as compared to controls at ICU discharge (15 [83%] vs. 9 [50%], P = 0.0339). ICU discharge survival was significantly higher in patients treated with PB (17 [94%] vs. 9 [50%], P = 0.0017). In cirrhotic patients with overt HE, sodium PB could be effective in reducing ammonia levels and might be effective in improving neurological status and ICU discharge survival. More extensive data, especially a RCT, are mandatory.

[Treatment of malignant non-Hodgkin's lymphoma. Economic impact of rituximab (Mabthera) versus conventional chemotherapy]. / Traitement des lymphomes malins non hodgkiniens. Répercussions économiques de l'utilisation du rituximab (Mabthera) versus chimiothérapies conventionnelles.

The monoclonal antibody rituximab, targeted against the CD20 antigen, has shown efficacy in patients with follicular lymphoma who relapse or fail to response to conventional chemotherapy. We evaluated the economic impact of using rituximab for the treatment of non-Hodgkin's lymphoma (NLH) in comparison with conventional chemotherapy protocols (CHOP or CHVP). In this retrospective study conducted between 1998 and 2000, the direct costs of treating inpatients with NHL rituximab (n=20) or CHOP/CHVP (n=17) were compared. Results, including costs of administering chemotherapy and adverse events, showed that the average cost per patient was comparable for the two strategies (9700 euro for rituximab, versus 8487 euro for conventional chemotherapy). In the rituximab group, the cost was mostly due to drug purchases. In the conventional chemotherapy group, outlays were related to drug-induced toxicity and longer hospital stay. Our results were similar to others described in the literature. Prospective studies are nevertheless needed for confirmation. For first-line treatement, the difference in the cost-effectiveness-ratio between rituximab and conventional drugs might be smaller, but sound data are not yet available.