Claus Moser

Rigshospitalet | rigshospitalet · Department of Clinical Microbiology

Background Transcatheter aortic valve implantation (TAVI) is a percutaneous catheter-based treatment of aortic stenosis as an alternative to open heart valve surgery. In cases of TAVI endocarditis, the treatment possibilities may be limited as surgical removal of the infected valve may be associated with a high risk in elderly, comorbid or frail pa...

Background Oral step-down antibiotic treatment (PO) was included in the 2023 ESC guidelines for treatment of infective endocarditis. In the nationwide POETry study(1), the use PO in patients with left-sided infective endocarditis (IE) was examined in Denmark, showing that almost half of possible candidates with left-sided IE received PO, with no si...

P. aeruginosa biofilms are aggregates of bacteria surrounded by a self-produced matrix which binds to some antibiotics such as aminoglycosides. P. aeruginosa biofilms are tolerant to antibiotics. The treatment of biofilm infections leads to a recurrence of symptoms after finishing antibiotic treatment, although the initial clinical response to the...

Background Increased prevalence of antimicrobial resistance coupled with a lack of new antibiotics against Gram-negative bacteria emphasize the imperative for novel therapeutic strategies. Colistin-resistant Pseudomonas aeruginosa constitutes a challenge, where conventional treatment options lack efficacy, in particular for biofilm-associated infec...

Infective endocarditis (IE) is a severe infection of the inner heart. Even with current standard treatment, the mean in‐hospital mortality is as high as 15–20%, and 1‐year mortality is up to 40% for left‐sided IE. Importantly, IE mortality rates have not changed substantially over the past 30 years, and the incidence of IE is rising. The treatment...

This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed t...

Introduction Antibiotic treatment of chronic biofilm-associated infections can be challenging. Characterization of pharmacokinetic-pharmacodynamic (PK-PD) relationships for biofilm-associated infections may be relevant to inform the design of antibiotic treatment regimens for biofilm-associated infections. To this end, we aim to develop a mathemati...

This paper presents the work done to transition the lab scale synthesis (1 g) to a large scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol; a new pharmaceutical for treatment of antibiotic resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab scale synthesis was transformed to a...

Persistent urinary tract infections (UTIs) in hospitalized patients constitute an important medical problem. It is estimated that 75% of nosocomial UTIs are associated with urinary tract catheters with P. aeruginosa being a species that forms biofilms on these catheters. These infections are highly resistant to standard-of-care antibiotics, and the...

Antibiotic susceptibility testing (AST) by agar diffusion has been repeatedly standardized and, in most cases, gives results which predict clinical success when antibiotic treatment is based on such results. The formation of the inhibition zone is due to a transition from planktonic to biofilm mode of growth. The kinetics of the interaction of anti...

The evolution of antimicrobial resistance (AMR) in biofilms has been repeatedly studied by experimental evolution in vitro, but rarely in vivo. The complex microenvironment at the infection site imposes selective pressures on the bacterial biofilms, potentially influencing the development of AMR. We report here the development of AMR in an in vivo...

Background and Aims In the Partial Oral Treatment of Endocarditis (POET) trial, stabilized patients with left-sided infective endocarditis (IE) were randomized to oral step-down antibiotic therapy (PO) or conventional continued intravenous antibiotic treatment (IV), showing non-inferiority after 6 months. In this study, the first guideline-driven c...

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 t...

Objectives An endovascular aneurysm repair (EVAR) graft is a catheter-implanted vascular prosthesis and is the preferred treatment for patients with aortic aneurysm. If an EVAR graft becomes the focus of infection, the treatment possibilities are limited because it is technically difficult to remove the graft to obtain source control. This study ex...

Background Biofilm antibiotic tolerance is partly explained by the behavior of a biofilm as an independent pharmacokinetic micro-compartment. Hyperbaric oxygen therapy has been shown to potentiate antibiotic effects in biofilms. The present study investigates the effect of hyperbaric oxygen therapy (HBOT) on the biofilm micro-pharmacokinetic/pharma...

Purpose In patients surviving infective endocarditis (IE) recurrence of bacteremia or IE is feared. However, knowledge is sparse on the incidence and risk factors for the recurrence of bacteremia or IE. Methods Using Danish nationwide registries (2010–2020), we identified patients with first-time IE which were categorized by bacterial species (Sta...

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)....

Objectives In the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD). However, data on plasma concentrations of these antibiotics during HD are sparse. This study aims to determine if the plasma concentration of amoxicillin and clindamycin...

Background Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods First-time SAB was identified from 2010 to 2018 using Danish nationwide registries...

Introduction Chronic wounds have a compromised microcirculation which leads to restricted gas exchange. The majority of these hypoxic wounds is infested with microorganisms congregating in biofilms which further hinders the antibiotic function. We speculate whether this process can be counteracted by hyperbaric oxygen therapy (HBOT). Methodology T...

Background Enterococcus faecalis is the third most common cause of infective endocarditis (IE) and has been associated with a higher risk of relapse and death. Within the enterococcus species, E. faecium is the second most frequent cause of IE. As IE from E. faecalis or E. faecium most likely have different presentations and outcomes, research is n...

Background Our knowledge of changes in vegetation size throughout the course of infective endocarditis (IE) and the impact of persistent vegetations on mortality or embolization after completed antibiotic treatment is sparse. No study has previously investigated the prevalence or clinical impact of persistent vegetations on transthoracic echocardio...

The failing eradication of bacterial biofilm by antibiotic treatment is a major clinical challenge for patients with chronic infections. The effect of re-sensitizing infectious biofilms to antibiotics by supplemental O2 has recently been explained by the pathophysiological conditions of the infectious microenvironment. In this chapter, we argue tha...

Introduction Urinary tract infections (UTIs) with Pseudomonas aeruginosa are a severe problem in disposed patients in modern healthcare. Pseudomonas aeruginosa establishes recalcitrant biofilm infections and can develop antibiotic resistance. Gargling with avian egg yolk anti- Pseudomonas antibodies (IgY) has shown clinical effect in preventing ons...

Biofilm infections are tolerant to the host responses and recalcitrance to antibiotic drugs and disinfectants. The induced host-specific innate and adaptive immune responses by established biofilms are significantly implicated and contributes to the course of the infections. Essentially, the host response may be the single one factor impacting the...

Background Monitoring of microbiological cause of infective endocarditis (IE) remains key in the understanding of IE; however, data from large, unselected cohorts are sparse. We aimed to examine temporal changes, patient characteristics, and in‐hospital and long‐term mortality, according to microbiological cause in patients with IE from 2010 to 201...

Background Valve surgery guidelines for infective endocarditis (IE) are unchanged over decades and nationwide data about the use of valve surgery do not exist. Methods We included patients with first-time IE (1999–2018) using Danish nationwide registries. Proportions of valve surgery were reported for calendar periods (1999–2003, 2004–2008, 2009–2...

Background We aimed to characterise the adaptive immune response to Mycobacterium abscessus complex (MABSC) and its cross-reactivity with Mycobacterium avium complex (MAC) and Mycobacterium bovis (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine p...

Acute wounds, such as thermal injury, and chronic wounds are challenging for patients and the health care system around the world. Thermal injury of considerable size induces immunosuppression, which renders the patient susceptible to wound infections, but also in other foci like the airways and urinary tract. Infected thermal lesions can progress...

Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a n...

Purpose Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. Methods This is a re-specified substudy of the randomized POET endocarditis trial, which in...

Infective endocarditis (IE) is one of the most severe infectious diseases with an in-hospital mortality of 20-25%. Several studies have shown, that the incidence of IE is increasing, and that patients now are older with a higher burden of comorbidities than previously. The diagnostic work-up is mainly based upon the presence of bacteraemia and echo...

Patients with infective endocarditis (IE) form a heterogeneous group by age, co-morbidities and severity ranging from stable patients to patients with life-threatening complications with need for intensive care. A large proportion need surgical intervention. In-hospital mortality is 15-20%. The concept of using hyperbaric oxygen therapy (HBOT) in o...

Chronic infections caused by microbial biofilms represent an important clinical challenge. The recalcitrance of microbial biofilms to antimicrobials and to the immune system is a major cause of persistence and clinical recurrence of these infections. In this Review, we present the extent of the clinical problem, and the mechanisms underlying the to...

Background The Partial-Oral versus Intravenous Antibiotic Treatment of Endocarditis Trial (POET) found that partial-oral outpatient treatment was non-inferior to conventional in-hospital intravenous treatment in patients with left-sided infective endocarditis. We examined the impact of treatment strategy on levels of anxiety and depression. Method...

The Danish National Partial Oral Treatment of Endocarditis Trial (POET) demonstrated non-inferiority of partly peroral compared to intravenous antibiotic therapy for infective endocarditis (IE) caused by Streptococcus spp, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci. Identifications by whole genome sequencing (...

Objectives The pathophysiology of chronic wounds is characterized by prolonged inflammation, low mitogenic-activity, high protease-/low inhibitor-activity, microbiota changes and biofilm formation, in combination with the etiology of the original insult. One strategy to promote healing is to terminate the parasitism-like-relationship between the bi...

Objective To assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality. Methods In the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation o...

Infective endocarditis (IE) is a heart valve infection with high mortality rates. IE results from epithelial lesions, inducing sterile healing vegetations consisting of platelets, leucocytes and fibrin that are susceptible for colonization by temporary bacteremia. Clinical testing of new treatments for IE is difficult and fast models sparse. The pr...

Infective endocarditis (IE) is a life-threatening infective disease with increasing incidence worldwide. From early on, in the antibiotic era, it was recognized that high-dose and long-term antibiotic therapy was correlated to improved outcome. In addition, for several of the common microbial IE etiologies, the use of combination antibiotic therapy...

Animal models of human diseases are invaluable and inevitable elements in identifying and testing novel treatments of serious diseases, including severe infections. Planning and conducting investigator initiated human trials are generally accepted as being enormously challenging. In contrast, it is often underestimated how much planning, including...

Staphylococcus aureus (SA) causes superficial and severe endovascular infections. The present in vitro study investigates the anti‐SA mechanisms of hyperbaric oxygen therapy (HBOT) on direct bacterial killing, antibiotic potentiation and polymorphonuclear leukocyte (PMN) enhancement. SA was exposed to isolated human PMNs, tobramycin, ciprofloxacin...

Necrotizing soft-tissue infection (NSTI) is a rare, severe, and fast-progressing bacterial infection associated with a high risk of developing sepsis or septic shock. Increasing evidence indicates that oxidative stress is crucial in the development and progression of sepsis, but its role in NSTI specifically has not been investigated. Some patients...

Objective Pseudomonas aeruginosa is known to contribute to the pathogenesis of chronic wounds by biofilm-establishment with increased tolerance to host response and antibiotics. The neutrophil-factor S100A8/A9 has a promising adjuvant effect when combined with ciprofloxacin, measured by quantitative bacteriology, and increased anti- and lowered pro...

Pseudomonas aeruginosa is a key pathogen of chronic infections in the lungs of cystic fibrosis patients and in patients suffering from chronic wounds of diverse etiology. In these infections the bacteria congregate in biofilms and cannot be eradicated by standard antibiotic treatment or host immune responses. The persistent biofilms induce a hyper...

The inflammatory response in patients with necrotizing soft-tissue infection (NSTI) is excessive and often causes collateral damage, thereby worsening disease severity and prognosis. Shedding of endothelial adhesion molecules may be a key regulatory mechanism to modulate the inflammatory response in septic NSTI patients. Hyperbaric oxygen (HBO 2 )...

Background Left-sided infectious endocarditis (IE) has a high 1-year mortality. Anemia is a common finding in patients with IE, yet little is known about frequency, severity, and associated outcomes in this setting. Purpose To examine the relationship between Hemoglobin (Hgb) level measured at IE stabilization (time of randomization) in the Partia...

Introduction Cystic fibrosis (CF) patients are at risk of acquiring chronic Pseudomonas aeruginosa lung infections. The biofilm mode of growth of P. aeruginosa induces tolerance to antibiotics and the host response; accordingly, treatment failure occurs. Supplemental azithromycin has proven beneficial in CF due to potential immunomodulatory mechani...

Background IL‐2 is a pro‐inflammatory and a Th1 inducing cytokine, which is important for activation of the cell‐mediated immunity. IL‐2 in serum and sputum has been observed to be reduced in cystic fibrosis (CF) patients. The present IL‐2 treatment study of Pseudomonas aeruginosa (PA) lung infected mice was performed in order to evaluate the effec...

Normal wound healing occurs in three phases—the inflammatory, the proliferative, and the remodeling phase. Chronic wounds are, for unknown reasons, arrested in the inflammatory phase. Bacterial biofilms may cause chronicity by arresting healing in the inflammatory state by mechanisms not fully understood. Pseudomonas aeruginosa, a common wound path...

Background The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to six weeks for patients with left sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE and compl...

Streptococcus gordonii and Streptococcus sanguinis belong to the Mitis group streptococci, which mostly are commensals in the human oral cavity. Though they are oral commensals, they can escape their niche and cause infective endocarditis, a severe infection with high mortality. Several virulence factors important for the development of infective e...

Fast and accurate detection of causative agents of bloodstream infections remains a challenge of today's microbiology. We compared the performance of cutting‐edge technology based on polymerase chain reaction coupled with electrospray ionization‐mass spectrometry (PCR/ESI‐MS) with that of conventional broad‐range 16S rRNA PCR and blood culture to a...

Background: Transcatheter aortic valve implantation (TAVI) has been approved for the treatment of severe aortic stenosis since 2008 and recent trials have shown that TAVI is a least non-inferior to surgical aortic valve replacement (SAVR) with regards to short-term efficacy and safety in patients across all surgical risk profiles. Prosthetic valve...

Background: Specific Pseudomonas aeruginosa (PA) precipitating immunoglobulin G antibodies in serum are correlated with PA biofilm infection and are used as diagnostic and prognostic markers in cystic fibrosis (CF). The aim of this study was to examine the change of PA antibody response in CF patients after bilateral sequential lung transplantatio...

Background: Pseudomonas aeruginosa is difficult to eradicate from the lungs of cystic fibrosis (CF) patients due to biofilm formation. Organs and blood are independent pharmacokinetic (PK) compartments. Previously, we showed in vitro biofilms behave as independent compartments impacting the pharmacodynamics. The present study investigated this phe...

Bacteria and fungi show substantial increased recalcitrance when growing as infectious biofilms. Chronic infections caused by biofilm growing microorganisms is considered a major problem of modern medicine. New strategies are needed to improve antibiotic treatment of biofilms. We have improved antibiotic treatment of bacterial biofilms by reviving...

Bacteria and fungi show substantial increased recalcitrance when growing as infectious biofilms. Chronic infections caused by biofilm growing microorganisms is considered a major problem of modern medicine. New strategies are needed to find new ways to improve antibiotic treatment of biofilms. We have improved antibiotic treatment of bacterial biof...

Background Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSI). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. Purpose To investigate the nationwide prevalence of diagnosed IE in BSIs with bacteria typically associat...

PURPOSE We examined the Pseudomonas aeruginosa (PA) antibody response in 20 chronically PA infected cystic fibrosis (CF) patients from the CF Centre Copenhagen after bilateral sequential lung transplantation (LTx). We hypothesized that the antibody response to PA would change after LTx due to removal of the infectious load and immunosuppressive the...

Aims: Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSIs). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE. Methods and...

The majority of chronic wounds are associated with bacterial biofilms recalcitrant to antibiotics and host responses.Immunomodulatory S100A8/A9 is suppressed in P. aeruginosa biofilms infected wounds. We aimed at investigating a possible additive effect between S100A8/A9 and ciprofloxacin against biofilms. Materials/methods: Thirty-two mice were...

Introduction: Bacteraemia in adult patients undergoing treatment for leukaemia is common and associated with profound morbidity and mortality. Infections related to the use of a central venous catheter (CVC) are difficult to eliminate with systemic antibiotics. Premature catheter removal is often due to retained biofilm infection. This study inves...

Background Staphylococcus aureus is the most frequent and fatal cause of left-sided infective endocarditis (IE). New treatment strategies are needed to improve the outcome. S. aureus coagulase promotes clot and fibrin formation. We hypothesized that dabigatran, could reduce valve vegetations and inflammation in S. aureus IE. Methods We used a rat...

Cytokines and adhesion molecules expression in aortic valve endocarditis. (DOCX)

Results of ROTEM performed in plasma samples. (DOCX)

Extended Material, Method and Results section. (PDF)

Flow cytometry of whole blood. Platelet-neutrophil complexes (PNC) (A), neutrophils (B) and total leukocyte count (TLC) (C) are shown for the two intervention groups. Horizontal lines represent means ± standard derivation. * indicate p < 0.05. n.s., non-significant. (TIF)

Histopathological assessment. (DOCX)