Continuous infusion of meropenem-vaborbactam for a KPC-3-producing Klebsiella pneumoniae bloodstream infection in a critically ill patient with augmented renal clearance.

PURPOSE: To demonstrate the feasibility of continuous infusion of meropenem-vaborbactam to optimize the treatment of carbapenem-resistant Enterobacterales. METHODS: Report of a case of a Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection comfirmed by whole genome sequencing and therapeutic drug monitoring (TDM) of meropenem. RESULTS: A patient with augmented renal clearance (ARC) went into septic shock caused by an ST11 KPC-3-producing K. pneumoniae bloodstream infection that was successfully treated with a continuous infusion of meropenem-vaborbactam at a dosage of 1 g/1 g q4h as a 4-h infusion. TDM confirmed sustained concentrations of meropenem ranging from 8 to 16 mg/L throughout the dosing interval. CONCLUSION: Continuous infusion of meropenem-vaborbactam was feasible. It could be appropriate for optimizing the management of critically ill patients with ARC, as it resulted in antibiotic concentrations above the minimum inhibitory concentration for susceptible carbapenem-resistant Enterobacterales (up to 8 mg/L) throughout the dosing interval.

Usefulness of dynamic regression time series models for studying the relationship between antimicrobial consumption and bacterial antimicrobial resistance in hospitals: a systematic review.

BACKGROUNG: Antimicrobial resistance (AMR) is on the rise worldwide. Tools such as dynamic regression (DR) models can correlate antimicrobial consumption (AMC) with AMR and predict future trends to help implement antimicrobial stewardship programs (ASPs). MAIN BODY: We carried out a systematic review of the literature up to 2023/05/31, searching in PubMed, ScienceDirect and Web of Science. We screened 641 articles and finally included 28 studies using a DR model to study the correlation between AMC and AMR at a hospital scale, published in English or French. Country, bacterial species, type of sampling, antimicrobials, study duration and correlations between AMC and AMR were collected. The use of ß-lactams was correlated with cephalosporin resistance, especially in Pseudomonas aeruginosa and Enterobacterales. Carbapenem consumption was correlated with carbapenem resistance, particularly in Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Fluoroquinolone use was correlated with fluoroquinolone resistance in Gram-negative bacilli and methicillin resistance in Staphylococcus aureus. Multivariate DR models highlited that AMC explained from 19 to 96% of AMR variation, with a lag time between AMC and AMR variation of 2 to 4 months. Few studies have investigated the predictive capacity of DR models, which appear to be limited. CONCLUSION: Despite their statistical robustness, DR models are not widely used. They confirmed the important role of fluoroquinolones, cephalosporins and carbapenems in the emergence of AMR. However, further studies are needed to assess their predictive capacity and usefulness for ASPs.

Clinical Features and Outcomes of Enterococcal Bone and Joint Infections and Factors Associated with Treatment Failure over a 13-Year Period in a French Teaching Hospital.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31-7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22-4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis.

Effect of antimicrobial consumption on Escherichia coli resistance: assessment and forecasting using Dynamic Regression models in a French university hospital (2014-2019).

INTRODUCTION: The aim of this study was to determine the correlation between antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in Escherichia coli at a hospital level, and assess the capacity of dynamic regression (DR) models to predict AMR for their use in deployment of antimicrobial stewardship programs (ASPs). METHODS: A retrospective epidemiological study was conducted in a French tertiary hospital between 2014 and 2019. DR models were used to assess the correlation between AMC and AMR from 2014 to 2018. The predictive abilities of the models were estimated by comparing the predicted data with those observed in 2019. RESULTS: Rates of fluoroquinolone and cephalosporin resistance decreased. AMC increased overall but decreased for fluoroquinolone. DR models highlighted that the decrease in use of fluoroquinolone and the increase in use of anti-pseudomonal activity penicillin with beta-lactamase inhibitor (AAPBI) explained 54% of the decrease in fluoroquinolone resistance and 15% of the decrease in cephalosporin resistance. In addition, penicillin/beta-lactamase inhibitor (PBI) consumption explained 53% of PBI resistance, and beta-lactam use explained 36% of penicillin resistance, with both remaining stable over time. DR models had predictive capabilities with margins of error from 8% to 34%. CONCLUSION: Over a six-year period in a French tertiary hospital, decreasing rates of resistance to fluoroquinolones and cephalosporins were correlated with decreasing use of fluoroquinolone and increasing use of AAPBI, whereas rates of resistance to penicillin remained high and stable. The results indicate that DR models should be used with caution for AMR forecasting and ASP implementation.

Evaluation of vaccination coverage in heart failure patients in a tertiary center.

Background: Despite current recommendation, vaccination coverage (VC) for patients with heart failure (HF) remains far too limited. Aims: To evaluate the VC of HF patients followed in our hospital center and investigate the barriers to vaccination and the ways to address them. Methods: This was a cross-sectional monocentric descriptive study conducted between December 2019 and January 2021 at the University Hospital of Montpellier, France. Patients with HF history hospitalized in cardiology unit (CU) and patients in a HF telemonitoring program (TP) were included. An interview was conducted by a pharmacist to find out the patient's vaccination status against influenza and pneumococcus. For non-vaccinated patients, opinion and willingness to be vaccinated were also obtained. Results: Data from 335 patients were collected (185 in CU, 150 in TP). The mean age was 69.3 years and the proportion of males was 72%. About 65% were vaccinated against influenza in the last year (60% in CU, 72% in TP, p = 0.022) and 22% were up to date with pneumococcal vaccination (11% in CU, 35% in TP, p < 0.001). Among patients not vaccinated, 17% refused vaccination. Among unvaccinated patients who consider vaccination, 69% wanted to be vaccinated by their general practitioner (GP). Conclusions: The VC of HF patients remains insufficient. Patients in TP are more vaccinated than patients in CU, which could involve better management. The low rate of vaccinated patients is mainly explained by a lack of awareness. The medical team, including the clinical pharmacist by his dedicated time during medication reconciliation may play a major role in the management of hospitalized patients as well as GP's as local actors.

Effect of Tocilizumab on Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta or Omicron Variants: A Propensity-Matched Analysis in Nimes University Hospital, France.

We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/- tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02-1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11-1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07-6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14-0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

Last resort beta-lactam antibiotics for treatment of New-Delhi Metallo-Beta-Lactamase producing Enterobacterales and other Difficult-to-Treat Resistance in Gram-negative bacteria: A real-life study.

Introduction: Novel last resort beta-lactam antibiotics are now available for management of infections due to New-Delhi Metallo-Beta-Lactamase (NDM) producing Enterobacterales and non-fermenters with Difficult-to-Treat Resistance. However, data regarding the use of imipenem-cilastatin-relebactam (IMI-REL), cefiderocol (CFD) and ceftazidime-avibactam plus aztreonam (CAZ-AVI-ATM) are scarce in real-life settings. This study aimed to describe the use of last resort beta-lactam antibiotics, the microbiology and the outcome, in patients hospitalized in a tertiary hospital. Methods: We conducted a monocentric observational cohort study from 2020/01/01, to 2022/08/31. We screened all patients admitted to Nimes University Hospital who have received ≥ 1 dose of last resort beta-lactam antibiotics during the study period, using the Pharmacy database. We included patients treated with IMI-REL, CFD and CAZ-AVI-ATM. The primary endpoint was the infection-free survival rate. We also calculated rates of microbiological and clinical cure, recurrent infection, death and adverse events. Results: Twenty-seven patients were included in the study and 30 treatment courses were analyzed: CFD (N=24; 80%), CAZ-AVI-ATM (N=3; 10%) and IMI-REL (N=3; 10%). Antibiotics were used in 21 males (70%) and 9 females (30%) with a median age at 65-year-old [50-73.5] and a median Charlson index at 1 [0-2]. Almost all the patients had ≥ 1 risk factor for carbapenem resistant bacteria, a half of them was hospitalized for severe COVID-19, and most of antibiotic courses (N=26; 87%) were associated with ICU admission. In the study population, the probability of infection-free survival at day-90 after last resort beta-lactam therapy initiation was 48.4% CI95% [33.2-70.5]. Clinical failure rate was at 30%, microbiological failure rate at 33% and mortality rate at 23%. Adverse events were documented in 5 antibiotic courses (17%). In details, P. aeruginosa were mainly treated with CFD and IMI-REL, S. maltophilia with CFD and CAZ-AVI-ATM, A. baumannii with CFD, and NDM producing-K. pneumoniae with CAZ-AVI-ATM and CFD. After a treatment course with CFD, CAZ-AVI-ATM and IMI-REL, the probability of infection-free survival was 48% CI95% [10.4-73.5], 33.3% CI95% [6.7-100], 66.7% CI95% [30-100], respectively. Discussion/conclusion: Use of last resort beta-lactam antimicrobials in real-life settings was a safe and efficient therapeutic option for severe infections related to Gram-negative bacteria with Difficult-to-Treat Resistance.