•First comparative study to evaluate therapeutic drug monitoring (TDM) in infective endocarditis (IE).•TDM enables a reduction in amoxicillin daily doses.•Amoxicillin recommended dosages for IE seem ...to be too high, particularly for streptococcal IE.•Individualized treatment for IE through TDM could decrease amoxicillin dose without prognosis concern.
International guidelines recommend high doses of β-lactams for most cases of infective endocarditis (IE). Therapeutic drug monitoring (TDM) is increasingly used to adjust β-lactam dose based on plasma concentrations, although there are no comparative studies to support this practice. The benefit of amoxicillin TDM during IE was evaluated.
An observational, retrospective, cohort study of adults treated with high-dose amoxicillin for enterococcal or streptococcal IE was conducted in two referral centers. Patients with, or without TDM were compared. The primary outcome was mean daily amoxicillin dose.
A total of 206 cases of streptococcal (n=140, 68%) or enterococcal (n=66, 32%) IE were included. IE occurred on prosthetic valves in 77 (37%) cases, and on intracardiac devices in 28 (14%) cases. Aortic valve was involved in 136 (66%) cases. There were 154 men (75%), mean age was 70 ± 14 years, valve surgery was performed in 81/206 (39%) patients, and in-hospital mortality was 8% (17/206). All patients in the TDM group and most patients in the group without TDM received amoxicillin as continuous infusion. Amoxicillin TDM was performed for 114 patients (55.3%), with a mean of 4.7 ± 2.3 measures per patient, a mean plasma steady-state concentration of 41.2 ± 19 mg/L, most (82/114, 72%) being within the therapeutic target (20–80 mg/L). Mean amoxicillin dose was lower in patients with TDM (10.0 ± 3.3 g/day) than those without TDM (11.3 ± 2.0 g/day) (P=0.003).
Amoxicillin TDM was associated with a reduction in daily doses, with no impact on adverse events and prognosis. Individualized treatment of IE through TDM may contribute to decreased use of antibiotics.
Campylobacter spp. bacteremia is a severe infection. A nationwide 5-year retrospective study was conducted to characterize its clinical features and prognostic factors.
The study included patients ...with Campylobacter spp. bacteremia diagnosed in 37 French hospitals participating in the surveillance network of the National Reference Center for Campylobacters and Helicobacters, from 1 January 2015 to 31 December 2019. The goal was to analyze the effects of a delay of appropriate antibiotic therapy and other risk factors on 30-day mortality rates, antibiotic resistance, patient characteristics, and prognosis according to the Campylobacter species.
Among the 592 patients, Campylobacter jejuni and Campylobacter fetus were the most commonly identified species (in 42.9% and 42.6%, respectively). The patients were elderly (median age 68 years), and most had underlying conditions, mainly immunodepression (43.4%), hematologic cancers (25.9%), solid neoplasms (23%), and diabetes (22.3%). C. jejuni and Campylobacter coli were associated with gastrointestinal signs, and C. fetus was associated with secondary localizations. Among the 80 patients (13.5%) with secondary localizations, 12 had endocarditis, 38 vascular, 24 osteoarticular, and 9 ascitic fluid infections. The 30-day mortality rate was 11.7%, and an appropriate antibiotic treatment was independently associated with 30-day survival (odds ratio, 0.47 95% confidence interval, .24-.93; P = .03). The median efficient therapy initiation delay was quite short (2 days interquartile range, 0-4 days) but it had no significant impact on the 30-day mortality rate (P = .78).
Campylobacter spp. bacteremia mainly occurred in elderly immunocompromised individuals with variable clinical presentations according to the species involved. Appropriate antimicrobial therapy was associated with improved 30-day survival.
The incidence of campylobacteriosis has substantially increased over the past decade, notably in France. Secondary localizations complicating invasive infections are poorly described. We aimed to ...describe vascular infection or endocarditis caused by Campylobacter spp. We included 57 patients from a nationwide 5-year retrospective study on Campylobacter spp. bacteremia conducted in France; 44 patients had vascular infections, 12 had endocarditis, and 1 had both conditions. Campylobacter fetus was the most frequently involved species (83%). Antibiotic treatment involved a β-lactam monotherapy (54%) or was combined with a fluoroquinolone or an aminoglycoside (44%). The mortality rate was 25%. Relapse occurred in 8% of cases and was associated with delayed initiation of an efficient antimicrobial therapy after the first symptoms, diabetes, and coexistence of an osteoarticular location. Cardiovascular Campylobacter spp. infections are associated with a high mortality rate. Systematically searching for those localizations in cases of C. fetus bacteremia may be warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Facing the nitrate pollution problem, the European Union has encouraged a code of “Good Agricultural Practices” (GAP) in order to recover a good chemical and ecological status of waterbodies. In this ...study, we hypothesized that the systematic application of GAP in time and space would allow to meet the EU standard of nitrate concentration (50 mg NO3 L−1) under arable cropping systems. Water and nitrogen fluxes were determined in an agricultural catchment (187 ha) during 22 years after GAP implementation, at field and catchment scales. The aquifer outlet is a set of springs which were monitored for water flow and nitrate concentration. GAP management mainly consisted in adjusting N fertilization rates and establishing catch crops. Crop N uptake, soil water and mineral N were measured respectively two and three times per year on 36 sites representing soil variability. These data were used to initialize the STICS model which simulated the fluxes of infiltrated water and nitrate leached below the rooting zone at field scale. The elementary fluxes (calculated for each site-year) were then used as independent inputs of the hydrological model MODCOU which made the integration at catchment scale. Simulations of agricultural scenarios allowed to calculate the cost/efficiency ratio of GAP implementation per soil type.
The mean amounts of infiltrated water and N leached calculated below rooting depth in agricultural fields were 179 mm yr−1 and 19 kg N ha−1 yr−1, respectively, yielding a mean weighted nitrate concentration of 41 mg NO3 L−1 during 22 years over the whole catchment. The mean residence time of water in the catchment was estimated at 17–22 years using tritium and CFC tracers. The observed nitrate concentration in the main spring declined 11 years after GAP implementation and levelled off to 49 mg NO3 L−1. The agro-hydrological model satisfactorily predicted water flow and nitrate concentration in springs but overestimated their response time. It predicted a positive impact of GAP application on water quality. GAP management appeared to be efficient on the long term with a low cost/efficiency ratio. A more flexible and motivating management could consist in including GAP as a first step in a loop progress towards agro-ecological systems.
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•Good Agricultural Practices (GAP) were applied for 22 years in a small arable basin.•GAP had positive impacts on nitrate losses, greater at field than at catchment scale.•The soil organic stock was stable in average whatever the soil type.•Leached N was five-fold more sensitive than wheat yield to soil water field capacity.•Water quality at outlet improved after a 11 yr delay (24 yrs simulated).
Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data ...on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies.
To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors.
This multicenter cohort study assessed surgical patients at 33 hospitals in 10 European countries who were recruited between December 16, 2016, and September 30, 2019 (follow-up through December 30, 2019). Enrolled patients were actively followed up for up to 90 days after surgery to assess the occurrence of S aureus SSIs and BSIs. Data analysis was performed between November 20, 2020, and April 21, 2022. All patients were 18 years or older and had undergone 11 different types of surgical procedures. They were screened for S aureus colonization in the nose, throat, and perineum within 30 days before surgery (source population). Both S aureus carriers and noncarriers were subsequently enrolled in a 2:1 ratio.
Preoperative S aureus colonization.
The main outcome was cumulative incidence of S aureus SSIs and BSIs estimated for the source population, using weighted incidence calculation. The independent association of candidate variables was estimated using multivariable Cox proportional hazards regression models.
In total, 5004 patients (median IQR age, 66 56-72 years; 2510 50.2% female) were enrolled in the study cohort; 3369 (67.3%) were S aureus carriers. One hundred patients developed S aureus SSIs or BSIs within 90 days after surgery. The weighted cumulative incidence of S aureus SSIs or BSIs was 2.55% (95% CI, 2.05%-3.12%) for carriers and 0.52% (95% CI, 0.22%-0.91%) for noncarriers. Preoperative S aureus colonization (adjusted hazard ratio AHR, 4.38; 95% CI, 2.19-8.76), having nonremovable implants (AHR, 2.00; 95% CI, 1.15-3.49), undergoing mastectomy (AHR, 5.13; 95% CI, 1.87-14.08) or neurosurgery (AHR, 2.47; 95% CI, 1.09-5.61) (compared with orthopedic surgery), and body mass index (AHR, 1.05; 95% CI, 1.01-1.08 per unit increase) were independently associated with S aureus SSIs and BSIs.
In this cohort study of surgical patients, S aureus carriage was associated with an increased risk of developing S aureus SSIs and BSIs. Both modifiable and nonmodifiable etiologic factors were associated with this risk and should be addressed in those at increased S aureus SSI and BSI risk.
Summary
Dickeya dadantii is a plant pathogen that secretes cell wall‐degrading enzymes (CWDE) that are responsible for soft‐rot symptoms. Virulence genes are expressed in a concerted manner and ...culminate when bacterial multiplication slows. We identify a 25 kb vfm cluster required for D. dadantii CWDE production and pathogenesis. The vfm cluster encodes proteins displaying similarities both with enzymes involved in amino acid activation and with enzymes involved in fatty acid biosynthesis. These similarities suggest that the vfm genes direct the production of a metabolite. Cell‐free supernatant from the D. dadantii wild‐type strain restores CWDE production in vfm mutants. Collectively, our results indicate that vfm genes direct the synthesis of an extracellular signal and constitute a new quorum sensing system. Perception of the signal is achieved by the two‐component system VfmH–VfmI, which activates the expression of the vfmE gene encoding an AraC regulator. VfmE then activates both the transcription of the CWDE genes and the expression of the vfm operons. The vfm gene cluster does not seem to be widespread among bacterial species but is conserved in other Dickeya species and could have been laterally transferred to Rahnella. This work highlights that entirely new families of bacterial languages remain to be discovered.
The survival of bacteria exposed to toxic compounds is a multifactorial phenomenon, involving well-known molecular mechanisms of resistance but also less-well-understood mechanisms of tolerance that ...need to be clarified. In particular, the contribution of biofilm formation to survival in the presence of toxic compounds, such as nickel, was investigated in this study. We found that a subinhibitory concentration of nickel leads Escherichia coli bacteria to change their lifestyle, developing biofilm structures rather than growing as free-floating cells. Interestingly, whereas nickel and magnesium both alter the global cell surface charge, only nickel promotes biofilm formation in our system. Genetic evidence indicates that biofilm formation induced by nickel is mediated by the transcriptional induction of the adhesive curli-encoding genes. Biofilm formation induced by nickel does not rely on efflux mechanisms using the RcnA pump, as these require a higher concentration of nickel to be activated. Our results demonstrate that the nickel-induced biofilm formation in E. coli is an adaptational process, occurring through a transcriptional effect on genes coding for adherence structures. The biofilm lifestyle is obviously a selective advantage in the presence of nickel, but the means by which it improves bacterial survival needs to be investigated.
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