Background: New treatment options for Mycobacterium abscessus infections are urgently needed. Since a correlation between MICs and clinical outcomes is not clearly established, potency of novel drugs needs to be evaluated using additional in vitro drug activity assays. Preclinical drug activity assays generally use the M.
View Article and Find Full Text PDFBackground: TBAJ-876 is a next-generation diarylquinoline. In vivo, diarylquinoline metabolites are formed with activity against Mycobacterium tuberculosis. Species-specific differences in parent drug-to-metabolite ratios might impact the translational value of animal model-based predictions.
View Article and Find Full Text PDFis an emerging opportunistic pathogen causing severe pulmonary infections in patients with underlying lung disease and cystic fibrosis in particular. The rising prevalence of infections poses an alarming threat, as the success rates of available treatment options are limited. Central to this challenge is the absence of preclinical models that accurately mimic conditions and that can reliably predict treatment outcomes in patients.
View Article and Find Full Text PDFBackground: Immunocompromised patients (ICPs) have an increased risk for a severe and prolonged COVID-19. SARS-CoV-2 monoclonal antibodies (mAbs) were extensively used in these patients, but data from randomized trials that focus on ICPs are lacking. We evaluated the clinical and virological outcome of COVID-19 in ICPs treated with mAbs across SARS-CoV-2 variants.
View Article and Find Full Text PDFReactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days.
View Article and Find Full Text PDFObjectives: Mycobacterium abscessus is an opportunistic respiratory pathogen in patients with underlying lung disease. It is infamously known for its low treatment success rates because of its resistance to multiple classes of antibiotics. Further insight into M.
View Article and Find Full Text PDFBackground: The Dutch Working Party on Antibiotic Policy (SWAB) in collaboration with relevant professional societies, has updated their evidence-based guidelines on empiric antibacterial therapy of sepsis in adults.
Methods: Our multidisciplinary guideline committee generated ten population, intervention, comparison, and outcome (PICO) questions relevant for adult patients with sepsis. For each question, a literature search was performed to obtain the best available evidence and assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.
Clin Infect Dis
February 2023
Background: Illness after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is less severe compared with previous variants. Data on the disease burden in immunocompromised patients are lacking. We investigated the clinical characteristics and outcomes of immunocompromised patients with coronavirus disease 2019 (COVID-19) caused by Omicron.
View Article and Find Full Text PDFPurpose: Because of the current lack of evidence-based antimicrobial treatment guidelines, Left Ventricular Assist Device (LVAD) infections are often treated according to local insights. Here, we propose a flowchart for protocolized treatment, in order to improve outcome.
Methods: The flowchart was composed based on literature, consensus and expert opinion statements.
Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with an increased incidence of thrombosis.
Objectives: By studying the fibrin network structure of coronavirus disease 2019 (COVID-19) patients, we aimed to unravel pathophysiological mechanisms that contribute to this increased risk of thrombosis. This may contribute to optimal prevention and treatment of COVID-19 related thrombosis.
Background: is a nontuberculous mycobacterium that causes skin and soft tissue infections. Treatment consists of multiple antibiotics, sometimes combined with surgical debridement. There is little evidence for the choice of antibiotics, the duration of treatment, and the role of susceptibility testing.
View Article and Find Full Text PDFGiven the low treatment success rates of drug-resistant tuberculosis (TB), novel TB drugs are urgently needed. The landscape of TB treatment has changed considerably over the last decade with the approval of three new compounds: bedaquiline, delamanid and pretomanid. Of these, delamanid and pretomanid belong to the same class of drugs, the nitroimidazoles.
View Article and Find Full Text PDFInfective endocarditis, osteomyelitis, and osteosynthesis-associated infections are mostly caused by Gram-positive bacteria. They are often difficult to treat and are associated with a poor prognosis. In the past 20 years, nine antibiotic drugs with predominant activity against Gram-positive bacteria have been introduced and approved by the Food and Drug Administration or the European Medicines Agency: ceftaroline, daptomycin, telavancin, dalbavancin, oritavancin, linezolid, tedizolid, delafloxacin, and omadacycline.
View Article and Find Full Text PDFInfections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.
View Article and Find Full Text PDFBackground: Given the persistently high global burden of tuberculosis, effective and shorter treatment options are needed. We explored the relationship between relapse and treatment length as well as interregimen differences for 2 novel antituberculosis drug regimens using a mouse model of tuberculosis infection and mathematical modeling.
Methods: Mycobacterium tuberculosis-infected mice were treated for up to 13 weeks with bedaquiline and pretomanid combined with moxifloxacin and pyrazinamide (BPaMZ) or linezolid (BPaL).
Background: The treatment success rate of drug-resistant (DR) tuberculosis is alarmingly low. Therefore, more effective and less complex regimens are urgently required.
Methods: We compared the efficacy of an all oral DR tuberculosis drug regimen consisting of bedaquiline (25 mg/kg), delamanid (2.
We describe the first patient with a left ventricular assist device (LVAD) driveline infection caused by Mycobacterium chelonae presenting with persistent infection despite conventional antibiotics. Treatment was successful with surgical debridement, driveline exit relocation, and a 4-month period of antibiotics. In the case of a culture-negative LVAD driveline infection, non-tuberculous mycobacteria should be considered.
View Article and Find Full Text PDFBackground: Despite intensive treatment regimens, the outcome of Mycobacterium abscessus infections is extremely poor and thus novel treatment regimens are needed. Although tigecycline seems to be one of the best options currently available, its long-term use is hampered by severe toxic side effects as well as the need for intravenous administration and the relatively high concentrations required for efficacy.
Objectives: To assess the in vitro activity of omadacycline against M.
The favorable treatment outcome rate for multidrug-resistant tuberculosis (MDR-TB) is only 54%, and therefore new drug regimens are urgently needed. In this study, we evaluated the activity of the combination of moxifloxacin and linezolid as a possible new MDR-TB regimen in a murine TB model and the value of the addition of the efflux pump inhibitor verapamil to this backbone. BALB/c mice were infected with drug-sensitive and were treated with human-equivalent doses of moxifloxacin (200 mg/kg of body weight) and linezolid (100 mg/kg) with or without verapamil (12.
View Article and Find Full Text PDFPreclinical treatment outcome evaluation of tuberculosis (TB) occurs primarily in mice. Current designs compare relapse rates of different regimens at selected time points, but lack information about the correlation between treatment length and treatment outcome, which is required to efficiently estimate a regimens' treatment-shortening potential. Therefore we developed a new approach.
View Article and Find Full Text PDFBeijing strains are associated with lower treatment success rates in tuberculosis (TB) patients. In contrast, laboratory strains such as H37Rv are often used in preclinical tuberculosis models. Therefore, we explored the impact of using a clinical Beijing strain on treatment outcome in our mouse tuberculosis model.
View Article and Find Full Text PDFNovel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity.
View Article and Find Full Text PDFObjectives: The mycobacterial cell wall is an effective permeability barrier that limits intracellular concentrations of anti-TB drugs and hampers the success of treatment. We hypothesized that colistin might enhance the efficacy of anti-TB drugs by increasing mycobacterial cell wall permeability. In this study, we investigated the additional effect of colistin on the activity of anti-TB drugs against Mycobacterium tuberculosis in vitro.
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