Impact of therapeutic drug monitoring of antibiotics in the management of infective endocarditis.

Treatment of infective endocarditis (IE) is based on high doses of antibiotics with a prolonged duration. Therapeutic drug monitoring (TDM) allows antibiotic prescription optimization and leads to a personalized medicine, but no study evaluates its interest in the management of IE. We conducted a retrospective, bicentric, descriptive study, from January 2007 to December 2019. We included patients cared for IE, defined according to Duke's criteria, for whom a TDM was requested. Clinical and microbiological data were collected after patients' charts review. We considered a trough or steady-state concentration target of 20 to 50 mg/L. We included 322 IE episodes, corresponding to 306 patients, with 78.6% (253/326) were considered definite according to Duke's criteria. Native valves were involved in 60.5% (185/306) with aortic valve in 46.6% (150/322) and mitral in 36.3% (117/322). Echocardiography was positive in 76.7% (247/322) of cases. After TDM, a dosage modification was performed in 51.5% (166/322) (decrease in 84.3% (140/166)). After initial dosage, 46.3% (82/177) and 92.8% (52/56) were considered overdosed, when amoxicillin and cloxacillin were used, respectively. The length of hospital stay was higher for patient overdosed (25 days versus 20 days (p = 0.04)), and altered creatinine clearance was associated with overdosage (p = 0.01). Our study suggests that the use of current guidelines probably leads to unnecessarily high concentrations in most patients. TDM benefits predominate in patients with altered renal function, but probably limit adverse effects related to overdosing in most patients.

Evolution of anti-SARS-CoV-2 immune response in a cohort of French healthcare workers followed for 7 months.

OBJECTIVES: We aimed to understand the immune response among healthcare workers (HCWs) following SARS-CoV-2 infection, and to determine the infection prevalence during the first wave of the pandemic among workers in our hospital. METHODS: Determination of the serological status against SARS-CoV-2 (nucleocapsid) was offered to all HCWs. All HCWs with positive SARS-CoV-2 serology were proposed to be included in a longitudinal medical and serological follow-up (anti-spike) for 7months. RESULTS: We included 3062 HCWs; 256 (8.4%) were positive for anti-SARS-CoV-2 nucleocapsid IgG. Among them, early decrease in the anti-nucleocapsid antibody index was observed between the first (S1) and second (S2) serology samplings in 208 HCWs (84.2%). The initial anti-nucleocapsid IgG index seemed to be related to the HCWs' age. Seventy-four HCWs were included in the 7-month cohort study. Among them, 69 (90.5%) had detectable anti-spike IgG after 7months and 24 (32.4%) reported persistent symptoms consistent with post-acute COVID-19 syndrome diagnosis. CONCLUSION: The prevalence of serological positivity among HCWs was 6.7%. Infection should be followed by vaccination because of antibody decrease.

Epidemiology and clinical characteristics of Klebsiella spp. meningitis in France.

OBJECTIVES: To describe the epidemiology of Klebsiella spp. meningitis in France with respect to clinical and bacteriological data. METHODS: We performed a four-year multicenter, retrospective, observational study. The primary objective was to provide a clinical description of patients with Klebsiella spp. meningitis. Secondary objectives were to compare community-acquired meningitis and healthcare-associated meningitis and to analyze factors associated with mortality. RESULTS: We enrolled 131 patients with Klebsiella spp. meningitis. Eighty-two (62.6%) infections were reported following neurosurgery. Twenty-eight strains (21.4%) were resistant to third-generation cephalosporins (3GC). The median [IQR] cellularity was 980/mm3 [116-5550], the median protein level was 5.67 [1.62-9] g/L and the median CSF glucose level was 2.5 [0-3.4] mmol/L. The in-hospital mortality rate was 23.6%. Community-acquired meningitis isolates were more frequently susceptible to 3GC than isolates from healthcare-associated meningitis (89.2% versus 72%; P=0.04). Comorbidities reported for patients with community-acquired meningitis were mainly diabetes mellitus and liver cirrhosis. In multivariate analysis, focal neurological disorder at the time of diagnosis was the only factor associated with in-hospital mortality (P=0.01). CONCLUSIONS: Purulent meningitis caused by Klebsiella spp. needs to be considered in patients with community-acquired meningitis and preexisting conditions, as well as in case of meningitis following neurosurgical procedures.

Is the second dose of vaccination useful in previously SARS-CoV-2-infected healthcare workers?

Vaccines are the most important public health measure to protect people from COVID-19 worldwide. In addition, healthcare workers account for a large number of infected people. Protecting this population from COVID-19 seems crucial to preserve healthcare systems. In a context of few doses available, serological assays could be useful to decide whether one or two doses are needed. Our results show that a first dose of BNT162b2 mRNA vaccine seems to act as a boost after SARS-CoV-2 infection in healthcare workers with a previous SARS-CoV-2 infection; a second dose might therefore not be required.

Relative faecal abundance of extended-spectrum ß-lactamase-producing Enterobacterales and its impact on infections among intensive care unit patients: a pilot study.

This pilot prospective study assessed the association between the faecal relative abundance of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) and the occurrence of ESBL-PE related infections. Twenty-four patients were included. The median ESBL relative abundance was 32.4%. The mean ESBL-PE relative abundance (ESBL-PE-RA) was more than five-fold higher in patients exposed during the last three months to antibiotics (P = 0.002). Furthermore, the mean ESBL relative abundance was more than two-fold higher in patients colonized with non-E. coli strains (P = 0.044). The mean ESBL-PE-RA was more than 10-fold higher for the concordant patients than for the discordant patients (59.1% vs 4.9%; P < 0.001).

Fosfomycin, from susceptibility to resistance: Impact of the new guidelines on breakpoints.

The fosfomycin breakpoint using the disc diffusion method (DDM) changed in the 2019 CA-SFM/EUCAST guidelines v2 (24mm versus 19mm). We assessed its impact on categorization of Enterobacterales recovered from urine samples in emergency departments. A total of 7749 and 2348 strains were tested using the DDM and the broth microdilution method (BMD), respectively. The DDM with the 19-mm breakpoint was in accordance with the BMD. Using the 24-mm breakpoint, the overall rate of fosfomycin resistance in Enterobacterales increased by three-fold (5.6% vs 18.1%, P<0.01) and reached 2.8% and 86.5% in E. coli and K. pneumoniae, respectively. French guidelines for the management of community-acquired UTI remain appropriate. The accuracy of the methods for routine fosfomycin susceptibility testing should be assessed. The role of fosfomycin in the treatment of documented CA-UTI due to Enterobacterales other than E. coli should be evaluated considering its rate of resistance and recent data reporting low accuracy.

Determination of Escherichia coli phylogroups in elderly patients with urinary tract infection or asymptomatic bacteriuria.

OBJECTIVES: Distinguishing between urinary tract infection (UTI) and asymptomatic bacteriuria (ABU) is difficult in the geriatric population since specific symptoms are often lacking. Escherichia coli is the most frequent UTI pathogen in this population but also a common urine colonizer. We hypothesized that detecting E. coli phylogroups B2 or D, which were previously associated with virulent strains responsible for extra-intestinal infections outside elderly patients, could help in distinguishing UTI from ABU. METHODS: Consecutive cases of E. coli bacteriuria diagnosed in hospitalized patients >75 years old during 3 months were investigated for E. coli phylogroups. Multiplex PCR was used to search for several virulence genes as previously described. Characteristics of UTI and ABU cases, assessed retrospectively according to definitions and geriatric expertise, were compared. RESULTS: Out of 233 bacteriuria cases, 60 were assessed to be UTI and 163 to be ABU, with 10 cases unclassified. E. coli strains belonging to the phylogroups B2 and D were significantly more frequent in UTI (48/60, 80%) than in ABU (101/163, 62%) by univariate and multivariate analyses (OR 3.05, 1.44-6.86, p 0.005). Out of all the host and bacterial characteristics studied, falls (p 0.032), comorbidities (p 0.041), and altered autonomy evaluated by a low activity of daily living score (p 0.027) were also associated with UTI using univariate and multivariate analysis. CONCLUSIONS: Determination of the E. coli phylogroup, in addition to some host characteristics, can help to distinguish UTI from ABU in elderly patients with bacteriuria. If this hypothesis is confirmed by prospective studies, then inappropriate use of antibiotics may be reduced in ABU cases.

Clinical impact of rapid bacterial identification by MALDI-TOF MS combined with the bêta-LACTA™ test on early antibiotic adaptation by an antimicrobial stewardship team in bloodstream infections.

BACKGROUND: Bloodstream infections (BSI) can potentially be life-threatening infections and are associated with a high crude mortality, moreover with an inappropriate first-line antibiotic therapy. Bacterial resistance is more and more frequently observed. New strategies of BSI management are urgently needed. MATERIALS AND METHODS: During an 18-months period, we prospectively evaluated the clinical impact of rapid bacterial identification by MALDI-TOF MS technology combined with an antimicrobial stewardship team (AST) intervention. Furthermore, during an 8-months period, we combined this strategy with the rapid detection of third-generation cephalosporin (3GC) resistance by the Bêta-LACTA™ test (BLT) directly on blood cultures. We then evaluated the theoretical impact of BLT on antibiotic therapy adaptation and establishment of infection control measures. RESULTS: A total of 335 blood cultures were enrolled during the study. MALDI-TOF MS gave accurate identification for 301 blood cultures (89,8%) and led to early antibiotic therapy adaptation for 73 episodes (21.8%). BLT was performed on 141 blood cultures, revealing 28 3GC-resistant bacteria (19.9%). Twenty-one patients (75%) received a non-adapted first-line treatment. The antibiotic therapy adaptation was delayed by 28.1 hours and the establishment of infection control measures by 35 hours with antimicrobial susceptibility testing, compared to the theoretical adaptation with BLT result. CONCLUSIONS: These tools can be included in a strategy of bloodstream infections management for a better patient care, optimizing and saving the use of antibiotics, notably carbapenems as well as diminishing the spread of multi-drug resistant bacteria by applying rapidly infection control measures.

Implementation of Alere i Influenza A & B point of care test for the diagnosis of influenza in an ED.

STUDY OBJECTIVE: This study aimed to evaluate the impact of implementing rapid point-of-care testing (POCT) with the Alere i Influenza A & B in an emergency department (ED) during an influenza epidemic. METHODS: Direct nasal swabs were prospectively collected following the physical examination of patients aged >18years who presented to the ED of a tertiary hospital in France with influenza-like illness (ILI) symptoms (N=301) between February 1st and March 31st, 2016, which coincided with an influenza epidemic. Laboratory-based testing (standard of care) was used to obtain a diagnosis in February 2016 (pre-POCT cohort) and positive results were confirmed using polymerase chain reaction. The primary endpoint was patient time in the ED. RESULTS: A total of 169 and 132 patients participated in the pre-POCT phase and POCT phase respectively. A significantly higher proportion of patients received a positive diagnosis in the POCT cohort compared with the pre-POCT cohort (31% versus 5.3%, P<0.01). Mean time spent in the ED and hospitalization rate were significantly lower in the POCT cohort (6.06h versus 4.15h, P=0.03, and 44.4% versus 9.7%, P=0.02, respectively). Despite similar rates in the prescription of antibiotics and antiviral therapies, the proportion of patients who were referred for additional tests was significantly lower in the POCT cohort (78.1% versus 62.1%, P=0.003, and 80.5% versus 63.6%, P=0.01, respectively). CONCLUSIONS: The Alere i Influenza A & B POCT reduced the length of stay in ED, the hospitalization rates, and the number of additional diagnostic tests compared with standard of care testing.