Rasmus HAre Jensen | SSI (original) (raw)

Papers by Rasmus HAre Jensen

Medical Mycology, 2020

Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility... more Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility and performance of methods currently used. The participants comprised 12 laboratories from French university hospitals (nine of them participating in the Modimucor study) and 11 laboratories participating in the Fungal PCR Initiative. For panel 1, three sera were each spiked with DNA from three different species (Rhizomucor pusillus, Lichtheimia corymbifera, Rhizopus oryzae). For panel 2, six sera with three concentrations of R. pusillus and L. corymbifera (1, 10, and 100 genomes/ml) were prepared. Each panel included a blind negative-control serum. A form was distributed with each panel to collect results and required technical information, including DNA extraction method, sample volume used, DNA elution volume, qPCR method, qPCR template input volume, qPCR total reaction volume, qPCR platform, and qPCR reagents used. For panel 1, assessing 18 different protocols, qualitative results (...

Journal of Fungi, 2022

Candida parapsilosis is the second most common cause of candidemia in some geographical areas and... more Candida parapsilosis is the second most common cause of candidemia in some geographical areas and in children in particular. Yet, the proportion among children varies, for example, from 10.4% in Denmark to 24.7% in Tehran, Iran. As this species is also known to cause hospital outbreaks, we explored if the relatively high number of C. parapsilosis pediatric cases in Tehran could in part be explained by undiscovered clonal outbreaks. Among 56 C. parapsilosis complex isolates, 50 C. parapsilosis were genotyped by Amplified Fragment Length Polymorphism (AFLP) fingerprinting and microsatellite typing and analyzed for nucleotide polymorphisms by FKS1 and ERG11 sequencing. AFLP fingerprinting grouped Iranian isolates in two main clusters. Microsatellite typing separated the isolates into five clonal lineages, of which four were shared with Danish isolates, and with no correlation to the AFLP patterns. ERG11 and FKS1 sequencing revealed few polymorphisms in ERG11 leading to amino-acid subst...

Journal of Fungi, 2019

Dear Friends and Colleagues,It is a great honor and pleasure for us to invite you cordially to pa... more Dear Friends and Colleagues,It is a great honor and pleasure for us to invite you cordially to participate in the 9th Congress on Trends in Medical Mycology (TIMM-9) [...]

International Journal of Antimicrobial Agents, 2017

Antifungal resistance can be intrinsic or acquired  Antifungal resistance relies on distinct and... more Antifungal resistance can be intrinsic or acquired  Antifungal resistance relies on distinct and sometimes combined mechanisms  Hsp90 and alterations in MSH2 may be significant genetic drivers of resistance  High genetic capacity of C. glabrata to acquire multidrug resistance is a concern

The British journal of dermatology, 2014

ABSTRACT In most European countries prevalence of onychomycosis varies between 3 and 22%(1-2) wit... more ABSTRACT In most European countries prevalence of onychomycosis varies between 3 and 22%(1-2) with Trichophyton rubrum accounting for 60 to more than 90% of infections.(3-4) Combination of microscopy with culture is still most commonly employed in routine laboratory practice worldwide. Direct microscopy is rapid, inexpensive and has a good sensitivity but does not allow discrimination of different fungal species. Culture on the other hand allows fungal species identification but has a low sensitivity particularly for nail specimens and is time consuming.(5) A few recent studies describe diagnostic molecular methods for direct detection of dermatophytes in the patient sample thereby providing a rapid and accurate diagnosis including species identification.(11-14) This article is protected by copyright. All rights reserved.

Current Opinion in Infectious Diseases, 2012

Purpose of review Recent advances in the molecular diagnostics of dermatophytosis may improve spe... more Purpose of review Recent advances in the molecular diagnostics of dermatophytosis may improve speed, specificities and sensitivities. This review provides an update on the current available molecular techniques for the diagnosis of dermatophytosis. Recent findings Molecular diagnostics of dermatophytosis relate to the direct detection of dermatophyte DNA in clinical specimens. Important challenges have been associated with the DNA extraction procedures, which despite improvement still lack consensus, and the fact that phenotypic species classification not always translates into distinct molecular taxonomic entities. Molecular methods are divided into conventional PCR, real-time PCR and post-PCR techniques. The former benefits from simplicity and being less expensive to implement, real-time PCR is less laborious, may enable a broader spectrum of simultaneous species detections and the closed system reduces contamination risk, whereas post-PCR strategies may increase the number of species identified but prolong the turnaround time, and the processing of PCR products increases the laboratory contamination risk. Summary Current molecular methods are on the verge of overcoming most of the early challenges regarding dermatophyte taxonomy, DNA extraction procedures and species specificity, and thus may lead to an increased adoption of such methods. This may point towards a novel consensus in which molecular methods supplement or even replace classical diagnosis of dermatophytosis.

Internal Medicine, 2007

Infective endocarditis, a serious infection most commonly affecting rheumatic or prosthetic valve... more Infective endocarditis, a serious infection most commonly affecting rheumatic or prosthetic valves, generally occurs after bacteremia. Atopic dermatitis, a very common disease, carries a high prevalence of skin infections, particularly with Staphylococcus aureus. While cutaneous colonization by S. aureus represents an important source of bacteremia, few cases of infective endocarditis arising from the skin lesions of atopic dermatitis have been reported. We describe a patient with recurrent S. aureus prosthetic valve endocarditis developing in this manner.

Antimicrobial Agents and Chemotherapy, 2015

The prevalence of intrinsic and acquired resistance among colonizing Candida isolates from patien... more The prevalence of intrinsic and acquired resistance among colonizing Candida isolates from patients after candidemia was investigated systematically in a 1-year nationwide study. Patients were treated at the discretion of the treating physician. Oral swabs were obtained after treatment. Species distributions and MIC data were investigated for blood and posttreatment oral isolates from patients exposed to either azoles or echinocandins for <7 or ≥7 days. Species identification was confirmed using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and internal transcribed spacer (ITS) sequencing, susceptibility was examined by EUCAST EDef 7.2 methodology, echinocandin resistance was examined by FKS sequencing, and genetic relatedness was examined by multilocus sequence typing (MLST). One hundred ninety-three episodes provided 205 blood and 220 oral isolates. MLST analysis demonstrated a genetic relationship for 90% of all paired blood and or...

Nature, 2022

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human... more The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation ...

M.C. Arendrup1, R.H. Jensen1, H.K. Johansen2, J.D. Knudsen3, L.E. Lemming4, B.L. Røder5, F.S. Ros... more M.C. Arendrup1, R.H. Jensen1, H.K. Johansen2, J.D. Knudsen3, L.E. Lemming4, B.L. Røder5, F.S. Rosenvinge6, L. Kristensen7, L. Nielsen8, B. Olesen8, E. Dzajic9, P. Kjældgård10, H.C. Schønheyder11 1Statens Serum Institut, Copenhagen, Denmark 2Rigshospitalet, Copenhagen, Denmark 3Hvidovre University Hospital, Hvidovre, Denmark 4Århus University Hospital, Århus, Denmark 5Slagelse Sygehus, Slagelse, Denmark 6Vejle Sygehus, Vejle, Denmark 7Herning Centralsygehus, Herning, Denmark 8Herlev University Hospital, Herlev, Denmark 9Esbjerg Sygehus, Esbjerg, Denmark 10Sønderborg Hospital, Sønderborg, Denmark 11Ålborg University Hospital, Alborg, Denmark

Frontiers in Cellular and Infection Microbiology, 2020

Guinea et al. Candida Widespread Genotypes Causing Candidemia A number of genotypes (7.2%; 52/723... more Guinea et al. Candida Widespread Genotypes Causing Candidemia A number of genotypes (7.2%; 52/723) were widespread (found at different hospitals), comprising 66.7% (52/78) of clusters, and involved patients at hospitals in the same city (n = 21) or in different cities (n = 31). Only one C. parapsilosis cluster was a widespread genotype found in all four countries. Around 11% of C. albicans and C. parapsilosis isolates causing candidemia are clusters that may result from patient-to-patient transmission, widespread genotypes commonly found in unrelated patients, or insufficient microsatellite typing genetic discrimination.

PLOS Pathogens, 2019

Aspergillus fumigatus is a saprobic fungus that may cause allergic syndromes, chronic pulmonary a... more Aspergillus fumigatus is a saprobic fungus that may cause allergic syndromes, chronic pulmonary aspergillosis (CPA), and acute invasive aspergillosis (IA). Many patients suffering from aspergillus diseases benefit from antifungal therapy. Itraconazole, voriconazole, posaconazole, and isavuconazole have been shown to be the most effective compounds for prevention and treatment of the various aspergillus diseases. The use of alternative antifungal drugs, i.e., liposomal amphotericin B, is limited by toxicity and the echinocandins by fungistatic activity, while both also require intravenous access. As a consequence, the triazoles have become the recommended option for first-line therapy and chemoprophylaxis [1,2]. Unfortunately, the effective use of triazoles has been threatened by the emergence of resistance in A. fumigatus [3]. In voriconazole-treated patients, day 42 survival was 21% lower in voriconazole-resistant IA compared with voriconazole-susceptible infection [4]. As the number of available drug classes is already very limited, some aspergillus diseases, such as central nervous system IA, are virtually untreatable if caused by a triazole-resistant isolate.

Antimicrobial Agents and Chemotherapy, 2019

In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported i... more In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton -infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum ( n = 12) or Trichophyton interdigitale ( n = 2) with elevated terbinafine MICs during 2013–2018 were included.

Antimicrobial Agents and Chemotherapy, 2015

The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 an... more The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera , 5 of Lichtheimia ramosa , 5 of group I and 9 of group II of Mucor circinelloides , 9 of Rhizomucor pusillus , 26 of Rhizopus microsporus , and 6 of Rhizopus oryzae . Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC 50 s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤0.03 to 0.5...

Medical Mycology, 2015

(EMBL) database accession numbers of the internal transcribed spacer (ITS) rDNA and β-tubulin (Bt... more (EMBL) database accession numbers of the internal transcribed spacer (ITS) rDNA and β-tubulin (Btub) for the case isolate of Trichophyton onychocola CCF 4802 are LN589976 and LN589971, respectively.

The Journal of antimicrobial chemotherapy, Jan 27, 2015

The objective of this study was to characterize the underlying molecular mechanisms in consecutiv... more The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance. Nine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for further studies. Relatedness was evaluated by MLST. Additional genes were analysed by sequencing (including FKS1, ERG11, ERG2 and TAC1) and gene expression by quantitative PCR (CDR1, CDR2 and ERG11). UV-spectrophotometry and GC-MS were used for sterol analyses. In vivo virulence was determined in the insect model Galleria mellonella and evaluated by log-rank Mantel-Cox tests. P-1 + P-2 were susceptible, P-3 + P-4 fluconazole resistant, P-5 pan-azole resistant, P-6 + P-7 pan-azole and echinocandin resistant and P-8 + P-9 MDR. MLST supported genetic relatedness among clinical isolates. P-4 harboured four changes in Erg11 (E266D, G307S, G450E and...

Medical mycology, 1998

Failures of drug treatment in fungal infections combined with improvements in performances and st... more Failures of drug treatment in fungal infections combined with improvements in performances and standardization of antifungal susceptibility testing have drawn attention to the problem of antifungal resistance and its underlying mechanisms. Resistance of Candida species and Cryptococcus neoformans to flucytosine (5FC) develops during monotherapy. Acquired resistance results from a failure to metabolize 5FC to 5FUTP and 5FdUMP, or from the loss of feedback control of pyrimidine biosynthesis. A combination of 5FC and amphotericin B (AmB) reduces the appearance of resistant C. albicans isolates. Resistance to AmB is unusual. C. lusitaniae is the most susceptible to AmB resistance. C. neoformans with decreased AmB susceptibility has been isolated from an HIV-infected patient. Acquired resistance to AmB is often associated with alteration of membrane lipids, especially ergosterol. Concomitant with the widespread use of fluconazole there have been increasing reports of fluconazole resistan...

Journal of Clinical Microbiology, 2010

Candida palmioleophila has previously been misidentified as C. famata or C. guilliermondii . We h... more Candida palmioleophila has previously been misidentified as C. famata or C. guilliermondii . We have investigated traditional and modern identification methods for the identification of this and related species. Forty-one clinical isolates previously identified as C. famata or C. guilliermondii and 8 reference strains were included. Color development on CHROMagar, growth temperature ranges, micromorphologies, carbon assimilation (ID32C), matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) profiles, and susceptibility profiles (mica- and anidulafungin and itra-, vori-, posa-, and fluconazole MICs were determined by EUCAST method EDef 7.1, and caspofungin MICs were determined by Etest) were determined, and results were compared to those of molecular identification (ITS1 and ITS2 sequencing). The following five different species were identified among the clinical isolates by sequencing, but no C. famata isolates were found: C. guilliermondii (22 ...

Clinical Microbiology and Infection, 2013

Significant changes in the management of fungaemia have occurred over the last decade with increa... more Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0-79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004-11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004-2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3-4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes.

Antimicrobial Agents and Chemotherapy, 2014

ABSTRACTEchinocandins are the preferred therapy for invasive infections due toCandida krusei. We ... more ABSTRACTEchinocandins are the preferred therapy for invasive infections due toCandida krusei. We present here a case of clinical failure involvingC. kruseiwith a characteristicFKS1hot spot mutation not previously reported inC. kruseithat was isolated after 14 days of treatment. Anidulafungin MICs were elevated by ≥5 dilution steps above the clinical breakpoint but by only 1 step for aCandida albicansisolate harboring the corresponding mutation, suggesting a notable species-specific difference in the MIC increase conferred by this mutation.

Medical Mycology, 2020

Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility... more Interlaboratory evaluations of Mucorales qPCR assays were developed to assess the reproducibility and performance of methods currently used. The participants comprised 12 laboratories from French university hospitals (nine of them participating in the Modimucor study) and 11 laboratories participating in the Fungal PCR Initiative. For panel 1, three sera were each spiked with DNA from three different species (Rhizomucor pusillus, Lichtheimia corymbifera, Rhizopus oryzae). For panel 2, six sera with three concentrations of R. pusillus and L. corymbifera (1, 10, and 100 genomes/ml) were prepared. Each panel included a blind negative-control serum. A form was distributed with each panel to collect results and required technical information, including DNA extraction method, sample volume used, DNA elution volume, qPCR method, qPCR template input volume, qPCR total reaction volume, qPCR platform, and qPCR reagents used. For panel 1, assessing 18 different protocols, qualitative results (...

Journal of Fungi, 2022

Candida parapsilosis is the second most common cause of candidemia in some geographical areas and... more Candida parapsilosis is the second most common cause of candidemia in some geographical areas and in children in particular. Yet, the proportion among children varies, for example, from 10.4% in Denmark to 24.7% in Tehran, Iran. As this species is also known to cause hospital outbreaks, we explored if the relatively high number of C. parapsilosis pediatric cases in Tehran could in part be explained by undiscovered clonal outbreaks. Among 56 C. parapsilosis complex isolates, 50 C. parapsilosis were genotyped by Amplified Fragment Length Polymorphism (AFLP) fingerprinting and microsatellite typing and analyzed for nucleotide polymorphisms by FKS1 and ERG11 sequencing. AFLP fingerprinting grouped Iranian isolates in two main clusters. Microsatellite typing separated the isolates into five clonal lineages, of which four were shared with Danish isolates, and with no correlation to the AFLP patterns. ERG11 and FKS1 sequencing revealed few polymorphisms in ERG11 leading to amino-acid subst...

Journal of Fungi, 2019

Dear Friends and Colleagues,It is a great honor and pleasure for us to invite you cordially to pa... more Dear Friends and Colleagues,It is a great honor and pleasure for us to invite you cordially to participate in the 9th Congress on Trends in Medical Mycology (TIMM-9) [...]

International Journal of Antimicrobial Agents, 2017

Antifungal resistance can be intrinsic or acquired  Antifungal resistance relies on distinct and... more Antifungal resistance can be intrinsic or acquired  Antifungal resistance relies on distinct and sometimes combined mechanisms  Hsp90 and alterations in MSH2 may be significant genetic drivers of resistance  High genetic capacity of C. glabrata to acquire multidrug resistance is a concern

The British journal of dermatology, 2014

ABSTRACT In most European countries prevalence of onychomycosis varies between 3 and 22%(1-2) wit... more ABSTRACT In most European countries prevalence of onychomycosis varies between 3 and 22%(1-2) with Trichophyton rubrum accounting for 60 to more than 90% of infections.(3-4) Combination of microscopy with culture is still most commonly employed in routine laboratory practice worldwide. Direct microscopy is rapid, inexpensive and has a good sensitivity but does not allow discrimination of different fungal species. Culture on the other hand allows fungal species identification but has a low sensitivity particularly for nail specimens and is time consuming.(5) A few recent studies describe diagnostic molecular methods for direct detection of dermatophytes in the patient sample thereby providing a rapid and accurate diagnosis including species identification.(11-14) This article is protected by copyright. All rights reserved.

Current Opinion in Infectious Diseases, 2012

Purpose of review Recent advances in the molecular diagnostics of dermatophytosis may improve spe... more Purpose of review Recent advances in the molecular diagnostics of dermatophytosis may improve speed, specificities and sensitivities. This review provides an update on the current available molecular techniques for the diagnosis of dermatophytosis. Recent findings Molecular diagnostics of dermatophytosis relate to the direct detection of dermatophyte DNA in clinical specimens. Important challenges have been associated with the DNA extraction procedures, which despite improvement still lack consensus, and the fact that phenotypic species classification not always translates into distinct molecular taxonomic entities. Molecular methods are divided into conventional PCR, real-time PCR and post-PCR techniques. The former benefits from simplicity and being less expensive to implement, real-time PCR is less laborious, may enable a broader spectrum of simultaneous species detections and the closed system reduces contamination risk, whereas post-PCR strategies may increase the number of species identified but prolong the turnaround time, and the processing of PCR products increases the laboratory contamination risk. Summary Current molecular methods are on the verge of overcoming most of the early challenges regarding dermatophyte taxonomy, DNA extraction procedures and species specificity, and thus may lead to an increased adoption of such methods. This may point towards a novel consensus in which molecular methods supplement or even replace classical diagnosis of dermatophytosis.

Internal Medicine, 2007

Infective endocarditis, a serious infection most commonly affecting rheumatic or prosthetic valve... more Infective endocarditis, a serious infection most commonly affecting rheumatic or prosthetic valves, generally occurs after bacteremia. Atopic dermatitis, a very common disease, carries a high prevalence of skin infections, particularly with Staphylococcus aureus. While cutaneous colonization by S. aureus represents an important source of bacteremia, few cases of infective endocarditis arising from the skin lesions of atopic dermatitis have been reported. We describe a patient with recurrent S. aureus prosthetic valve endocarditis developing in this manner.

Antimicrobial Agents and Chemotherapy, 2015

The prevalence of intrinsic and acquired resistance among colonizing Candida isolates from patien... more The prevalence of intrinsic and acquired resistance among colonizing Candida isolates from patients after candidemia was investigated systematically in a 1-year nationwide study. Patients were treated at the discretion of the treating physician. Oral swabs were obtained after treatment. Species distributions and MIC data were investigated for blood and posttreatment oral isolates from patients exposed to either azoles or echinocandins for <7 or ≥7 days. Species identification was confirmed using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and internal transcribed spacer (ITS) sequencing, susceptibility was examined by EUCAST EDef 7.2 methodology, echinocandin resistance was examined by FKS sequencing, and genetic relatedness was examined by multilocus sequence typing (MLST). One hundred ninety-three episodes provided 205 blood and 220 oral isolates. MLST analysis demonstrated a genetic relationship for 90% of all paired blood and or...

Nature, 2022

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human... more The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation ...

M.C. Arendrup1, R.H. Jensen1, H.K. Johansen2, J.D. Knudsen3, L.E. Lemming4, B.L. Røder5, F.S. Ros... more M.C. Arendrup1, R.H. Jensen1, H.K. Johansen2, J.D. Knudsen3, L.E. Lemming4, B.L. Røder5, F.S. Rosenvinge6, L. Kristensen7, L. Nielsen8, B. Olesen8, E. Dzajic9, P. Kjældgård10, H.C. Schønheyder11 1Statens Serum Institut, Copenhagen, Denmark 2Rigshospitalet, Copenhagen, Denmark 3Hvidovre University Hospital, Hvidovre, Denmark 4Århus University Hospital, Århus, Denmark 5Slagelse Sygehus, Slagelse, Denmark 6Vejle Sygehus, Vejle, Denmark 7Herning Centralsygehus, Herning, Denmark 8Herlev University Hospital, Herlev, Denmark 9Esbjerg Sygehus, Esbjerg, Denmark 10Sønderborg Hospital, Sønderborg, Denmark 11Ålborg University Hospital, Alborg, Denmark

Frontiers in Cellular and Infection Microbiology, 2020

Guinea et al. Candida Widespread Genotypes Causing Candidemia A number of genotypes (7.2%; 52/723... more Guinea et al. Candida Widespread Genotypes Causing Candidemia A number of genotypes (7.2%; 52/723) were widespread (found at different hospitals), comprising 66.7% (52/78) of clusters, and involved patients at hospitals in the same city (n = 21) or in different cities (n = 31). Only one C. parapsilosis cluster was a widespread genotype found in all four countries. Around 11% of C. albicans and C. parapsilosis isolates causing candidemia are clusters that may result from patient-to-patient transmission, widespread genotypes commonly found in unrelated patients, or insufficient microsatellite typing genetic discrimination.

PLOS Pathogens, 2019

Aspergillus fumigatus is a saprobic fungus that may cause allergic syndromes, chronic pulmonary a... more Aspergillus fumigatus is a saprobic fungus that may cause allergic syndromes, chronic pulmonary aspergillosis (CPA), and acute invasive aspergillosis (IA). Many patients suffering from aspergillus diseases benefit from antifungal therapy. Itraconazole, voriconazole, posaconazole, and isavuconazole have been shown to be the most effective compounds for prevention and treatment of the various aspergillus diseases. The use of alternative antifungal drugs, i.e., liposomal amphotericin B, is limited by toxicity and the echinocandins by fungistatic activity, while both also require intravenous access. As a consequence, the triazoles have become the recommended option for first-line therapy and chemoprophylaxis [1,2]. Unfortunately, the effective use of triazoles has been threatened by the emergence of resistance in A. fumigatus [3]. In voriconazole-treated patients, day 42 survival was 21% lower in voriconazole-resistant IA compared with voriconazole-susceptible infection [4]. As the number of available drug classes is already very limited, some aspergillus diseases, such as central nervous system IA, are virtually untreatable if caused by a triazole-resistant isolate.

Antimicrobial Agents and Chemotherapy, 2019

In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported i... more In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton -infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum ( n = 12) or Trichophyton interdigitale ( n = 2) with elevated terbinafine MICs during 2013–2018 were included.

Antimicrobial Agents and Chemotherapy, 2015

The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 an... more The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera , 5 of Lichtheimia ramosa , 5 of group I and 9 of group II of Mucor circinelloides , 9 of Rhizomucor pusillus , 26 of Rhizopus microsporus , and 6 of Rhizopus oryzae . Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC 50 s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤0.03 to 0.5...

Medical Mycology, 2015

(EMBL) database accession numbers of the internal transcribed spacer (ITS) rDNA and β-tubulin (Bt... more (EMBL) database accession numbers of the internal transcribed spacer (ITS) rDNA and β-tubulin (Btub) for the case isolate of Trichophyton onychocola CCF 4802 are LN589976 and LN589971, respectively.

The Journal of antimicrobial chemotherapy, Jan 27, 2015

The objective of this study was to characterize the underlying molecular mechanisms in consecutiv... more The objective of this study was to characterize the underlying molecular mechanisms in consecutive clinical Candida albicans isolates from a single patient displaying stepwise-acquired multidrug resistance. Nine clinical isolates (P-1 to P-9) were susceptibility tested by EUCAST EDef 7.2 and Etest. P-4, P-5, P-7, P-8 and P-9 were available for further studies. Relatedness was evaluated by MLST. Additional genes were analysed by sequencing (including FKS1, ERG11, ERG2 and TAC1) and gene expression by quantitative PCR (CDR1, CDR2 and ERG11). UV-spectrophotometry and GC-MS were used for sterol analyses. In vivo virulence was determined in the insect model Galleria mellonella and evaluated by log-rank Mantel-Cox tests. P-1 + P-2 were susceptible, P-3 + P-4 fluconazole resistant, P-5 pan-azole resistant, P-6 + P-7 pan-azole and echinocandin resistant and P-8 + P-9 MDR. MLST supported genetic relatedness among clinical isolates. P-4 harboured four changes in Erg11 (E266D, G307S, G450E and...

Medical mycology, 1998

Failures of drug treatment in fungal infections combined with improvements in performances and st... more Failures of drug treatment in fungal infections combined with improvements in performances and standardization of antifungal susceptibility testing have drawn attention to the problem of antifungal resistance and its underlying mechanisms. Resistance of Candida species and Cryptococcus neoformans to flucytosine (5FC) develops during monotherapy. Acquired resistance results from a failure to metabolize 5FC to 5FUTP and 5FdUMP, or from the loss of feedback control of pyrimidine biosynthesis. A combination of 5FC and amphotericin B (AmB) reduces the appearance of resistant C. albicans isolates. Resistance to AmB is unusual. C. lusitaniae is the most susceptible to AmB resistance. C. neoformans with decreased AmB susceptibility has been isolated from an HIV-infected patient. Acquired resistance to AmB is often associated with alteration of membrane lipids, especially ergosterol. Concomitant with the widespread use of fluconazole there have been increasing reports of fluconazole resistan...

Journal of Clinical Microbiology, 2010

Candida palmioleophila has previously been misidentified as C. famata or C. guilliermondii . We h... more Candida palmioleophila has previously been misidentified as C. famata or C. guilliermondii . We have investigated traditional and modern identification methods for the identification of this and related species. Forty-one clinical isolates previously identified as C. famata or C. guilliermondii and 8 reference strains were included. Color development on CHROMagar, growth temperature ranges, micromorphologies, carbon assimilation (ID32C), matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) profiles, and susceptibility profiles (mica- and anidulafungin and itra-, vori-, posa-, and fluconazole MICs were determined by EUCAST method EDef 7.1, and caspofungin MICs were determined by Etest) were determined, and results were compared to those of molecular identification (ITS1 and ITS2 sequencing). The following five different species were identified among the clinical isolates by sequencing, but no C. famata isolates were found: C. guilliermondii (22 ...

Clinical Microbiology and Infection, 2013

Significant changes in the management of fungaemia have occurred over the last decade with increa... more Significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. These changes may impact the epidemiology of fungaemia. We present nationwide data for Denmark from 2010 to 2011. A total of 1081 isolates from 1047 episodes were recorded in 995 patients. The numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14.1%, respectively, from 2010 to 2011. The incidence rate was significantly higher in 2011 (10.05/100 000) than in 2010 (8.82/100 000), but remained constant in the age groups 0-79 years. The incidence rate was highest at the extremes of age and in males. Candida albicans accounted for 52.1% but declined during 2004-11 (p 0.0155). Candida glabrata accounted for 28% and increased during 2004-2011 (p <0.0001). Candida krusei, Candida tropicalis and Candida parapsilosis remained rare (3.3-4.2%). The species distribution changed with increasing age (fewer C. parapsilosis and more C. glabrata) and by study centre. Overall, the susceptibility rates were: amphotericin B 97.3%, anidulafungin 93.8%, fluconazole 66.7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes.

Antimicrobial Agents and Chemotherapy, 2014

ABSTRACTEchinocandins are the preferred therapy for invasive infections due toCandida krusei. We ... more ABSTRACTEchinocandins are the preferred therapy for invasive infections due toCandida krusei. We present here a case of clinical failure involvingC. kruseiwith a characteristicFKS1hot spot mutation not previously reported inC. kruseithat was isolated after 14 days of treatment. Anidulafungin MICs were elevated by ≥5 dilution steps above the clinical breakpoint but by only 1 step for aCandida albicansisolate harboring the corresponding mutation, suggesting a notable species-specific difference in the MIC increase conferred by this mutation.