Search

Background: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci., Objectives: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated., Patients and Methods: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination., Results: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively., Conclusions: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs)., Methods: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated., Results: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics., Conclusions: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis., Competing Interests: Potential conflicts of interest. C. T. P. reports a grant from Bayer for a randomized study, and a grant from Novo Nordisk for an epidemiological study. L. K. reports payment for speaking engagements from AstraZeneca, Bayer, Boehringer, and Novartis. C. M. reports payment for speaking engagements from AstraZeneca, GSK, MSD, and Pfizer; co-authorship of the Danish Treatment Guidelines for Infective Endocarditis and of the ESCMID guidelines for prevention, treatment and diagnosis of biofilm infections; and service as a board member of the European Society for Clinical Microbiology Study Group (ESCMID) for Biofilms (ESGB). E. L. F. reports grants from Novo Nordisk Foundation and the Danish Heart Association. N. E. B. reports grants from Novo Nordisk Foundation, Health Insurance Denmark, and Augustinus Foundation (all unrelated to this study). F. S. R. reports unpaid positions on the Danish Ministry of Health's National expert advisory board on antimicrobial stewardship, the Region of Southern Denmark's Regional working group on antimicrobial stewardship, and chairman on the Steering committee and working group at Odense University Hospital for rational use of antimicrobial drugs. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

High-resolution (or "cross-correlation") electron backscatter diffraction analysis (HR-EBSD) utilizes cross-correlation techniques to determine relative orientation and distortion of an experimental electron backscatter diffraction pattern with respect to a reference pattern. The integrity of absolute strain and tetragonality measurements of a standard Si/SiGe material have previously been analyzed using reference patterns produced by kinematical simulation. Although the results were promising, the noise levels were significantly higher for kinematically produced patterns, compared with real patterns taken from the Si region of the sample. This paper applies HR-EBSD techniques to analyze lattice distortion in an Si/SiGe sample, using recently developed dynamically simulated patterns. The results are compared with those from experimental and kinematically simulated patterns. Dynamical patterns provide significantly more precision than kinematical patterns. Dynamical patterns also provide better estimates of tetragonality at low levels of distortion relative to the reference pattern; kinematical patterns can perform better at large values of relative tetragonality due to the ability to rapidly generate patterns relating to a distorted lattice. A library of dynamically generated patterns with different lattice parameters might be used to achieve a similar advantage. The convergence of the cross-correlation approach is also assessed for the different reference pattern types.

Background: Pneumococcal infections have historically played a major role in terms of morbidity and mortality. We explored historical trends of invasive pneumococcal disease (IPD) and pneumococcal serotypes in a population exposed to limited antibiotic selective pressure and conjugate pneumococcal vaccination (PCV)., Methods: Retrospective cohort study based on nationwide laboratory surveillance data on IPD collected uninterruptedly in Denmark during 1938-2007. Changes in the reported incidence and trends of pneumococcal serotypes were explored using nonlinear regression analysis., Results: There were 25,502 IPD cases included in our study. The median incidence of IPD increased from 2.8 cases per 100,000 population (interquartile range [IQR], 1.5-2.6) during the first 4 decades to 15.7 cases per 100,000 population (IQR, 7-20.4) during the 1980s and 1990s, mainly attributed to an increase in the number of bacteremia cases. The incidence of meningitis remained relatively stable, with a median of 1.3 cases per 100,000 population (IQR, 0.9-1.6). The proportions of serotypes/groups 4 and 9 increased; the proportion of serotype 18C decreased; the proportions of serotypes 6, 7F, 14, and 23F remained stable; and serotype 2 nearly disappeared. Before the 1960s, serotypes 1, 2, 3, and 5 presented peaks every 2-3 years, becoming less frequent during the 1970s with peaks every 7-10 years. Between 20% and 90% of IPD in children <5 years were caused by PCV serotypes during the last 4 decades. Cases of IPD caused by serotype 19A increased before introduction of PCV. Between 1993 and 2007, the level of resistance to macrolides and beta-lactams was 6%., Conclusions: The epidemiology of IPD and single serotypes has constantly changed over the past 7 decades. PCV serotypes appeared to dominate the pneumococcal population.

Background: To elucidate how contraceptive attitudes among Danish-born and immigrant women influence the request of induced abortion., Methods: A case-control study, the case group comprising 1095 Danish-born women and 233 immigrant women requesting abortion, in comparison with a control group of 1295 pregnant women intending to give birth. The analysis used hospital-based questionnaire interviews., Results: Lack of contraceptive knowledge and experience of contraceptive problems were associated with the choice of abortion. This association was most pronounced among immigrant women, where women lacking knowledge had a 6-fold increased odds ratio (OR) and women having experienced problems a 5-fold increased OR for requesting abortion. Further, in this group of women, a partner's negative attitude towards contraception was associated with an 8-fold increased OR for requesting abortion. Contraceptive failure was prevalent; 21% of the women who did not plan to become pregnant but intended to give birth had experienced contraceptive failure. The same applied, respectively, for 45% of the Danish-born women and 36% of immigrant women, who requested abortion. Women who had experienced contraceptive failure were significantly more likely to request abortion., Conclusions: Immigrant women seem to have more difficulties in using contraception than Danish-born women. To address this problem, there is a need for culturally sensitive information campaigns targeting this heterogonous group of women.

Aerococcus urinae is a newcomer in clinical and microbiological practice, causing urinary tract infections, bacteraemia/septicaemia and/or endocarditis. This study presents for the first time an evaluation of the activity of a representative panel of antibiotics against a large number of A. urinae isolates. The in vitro susceptibilities (MICs) of 56 isolates of A. urinae to 14 antibiotics were determined by agar dilution. In general, A. urinae isolates showed little inter-isolate variability, and had low MICs of penicillin, amoxicillin, piperacillin, cefepime, vancomycin and rifampicin. High-level aminoglycoside resistance was not found for any of the isolates. Moderate to good activity was seen with quinolones, erythromycin and tetracycline. Isolates from two patients with endocarditis were studied with time-kill curves for penicillin, gentamicin and vancomycin. Penicillin and vancomycin alone exhibited slow or no bactericidal activity against the two strains. When combining either penicillin or vancomycin with gentamicin, rapid bactericidal activity was obtained for both strains with both combinations. The treatment options for A. urinae seem to include penicillins for less severe cases. In severe cases, i.e. endocarditis, the time-kill investigations suggest a beneficial effect of combination with gentamicin. In the penicillin-allergic patient vancomycin in combination with gentamicin represents the most obvious alternative.

Recently, some Aerococcus-like organisms (ALOs), isolated from urine and blood of elderly patients with urinary tract infection, have been described. In this study ALOs and related taxons were tested for susceptibility by agar diffusion and agar dilution methods to 15 selected antimicrobial agents for diagnostic and taxonomic considerations. ALOs were susceptible to a wide range of antimicrobials including beta-lactams, but resistant to aminoglycosides, sulphonamides, trimethoprim and nalidixic acid. By using tablets containing vancomycin, furazolidone and bacitracin, it was possible to separate ALOs from related taxons. Clustering based on antibiotic susceptibilities showed that there is little similarity between Aerococcus viridans and ALOs.

Some Aerococcus-like organisms (ALOs) have recently been described in Denmark. The bacteria were originally isolated from the urine of elderly patients with urinary tract infections. Since 1987, we have identified 17 cases of bacteremia/septicemia in which ALOs have been isolated in pure culture of blood; we report the data from these cases. Six of the patients presented with endocarditis, eight presented with urosepticemia, and three presented with septicemia. In all but one of the reports, the urinary tract was suspected as the focus of infection, and ALOs were isolated from the urine of nine patients. All but one patient had predisposing illnesses; these were predominantly of urinary or cardiac origin. Five patients died of their infection, two survived the infection but eventually died during hospitalization, and 10 recovered. All of the patients received adequate antimicrobial therapy.

80 clinical Branhamella catarrhalis strains of worldwide origin were examined for genotypic relatedness and phenotypic characteristics. Using a quantitative bacterial dot method for DNA-DNA hybridization the strains were found to form a homogeneous group with delta Tm-values ranging from 0.0-2.3 degrees C, In Minibact-N, an identification kit for oxidase positive, Gram-negative diplococci using eight phenotypic characteristics, all isolates were correctly identified and also demonstrated complete homogeneity except for beta-lactamase production. Type strains representing the genera Branhamella, Moraxella and Neisseria were also examined for comparison. B. catarrhalis strain NCTC 4103-known to be atypical-had a delta Tm-value of 5.7 degrees C and produced gamma-glutamylaminopeptidase, in contrast to all other B. catarrhalis strains. In GN MicroPlate, a kit which tests utilizable carbon sources, B. catarrhalis strains were found to be able to utilize up to 16 to 95 carbon sources.