European Journal of Clinical Microbiology & Infectious Diseases, Sep 10, 2011
Due to a longstanding comprehensive "search and destroy policy", methicillin-re... more Due to a longstanding comprehensive "search and destroy policy", methicillin-resistant Staphylococcus aureus (MRSA) is not endemic in Western Australian (WA) acute care hospitals. As the prevalence of MRSA in the community has increased, healthcare workers (HCW) are at risk of importing MRSA into hospitals. We aimed to determine the prevalence of and risk factors for nasal MRSA colonization in our HCW population. A period prevalence study was conducted at an 850-bed tertiary hospital. Basic demographics and a nasal swab were obtained. A total of 1,542 HCWs employed in our centre were screened for MRSA, of whom 3.4% (n = 52) were colonized. MRSA colonization was more common in patient care assistants (6.8%) and nurses (5.2%) than in allied health professionals (1.7%) and doctors (0.7%) (p < 0.01). Working in "high-risk" wards that cared for MRSA colonized/infected patients was the strongest risk factor for HCW MRSA colonization (p < 0.001). ST1-IV and ST78-IV (the most common community clones in the region) were the most frequently identified clones. In conclusion, MRSA colonization of HCWs occurs primarily in HCWs caring for patients colonized or infected with MRSA. Surveillance screening of HCWs should be regularly performed on wards with patients with high MRSA colonization prevalence to prevent further spread in the hospital.
Objectives The dolutegravir/valproic acid drug–drug interaction (DDI) is suggested to be caused b... more Objectives The dolutegravir/valproic acid drug–drug interaction (DDI) is suggested to be caused by protein displacement. Here, we assess the underlying mechanism. Methods Participants in a randomized controlled trial investigating valproic acid as an HIV latency reversing agent were recruited in a predefined pharmacokinetic substudy if they were on once-daily 50 mg dolutegravir-containing combination ART (cART) for >12 months with a plasma HIV-RNA <50 copies/mL (trial registration: ClinicalTrials.gov NCT03525730). Participants were randomized to receive 30 mg/kg/day valproic acid orally (divided into two equal doses) for 14 days or not. Total and unbound dolutegravir concentrations were measured on day 0 (before intake of valproic acid and 6 h after intake of valproic acid) and on days 1, 7, 14 and 42. Intra- and inter-subject dolutegravir concentrations and geometric means (GMs) were evaluated. Results Six of 10 participants on dolutegravir were randomized to receive valproic...
Samenvatting Infecties in het hart en de bloedbaan worden intravasale of endovasculaire infecties... more Samenvatting Infecties in het hart en de bloedbaan worden intravasale of endovasculaire infecties genoemd. De circulatie van bloed door het hart is essentieel voor de aanvoer van zuurstof en voedingstoffen naar weefsel en organen en voor de afvoer van afvalstoffen.
Nederlands tijdschrift voor geneeskunde, Jan 28, 2006
The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Poli... more The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Policy) has developed an evidence-based guideline for the empirical antimicrobial treatment of complicated urinary tract infections (UTIs) in hospitalised adult patients. The choice of treatment is based on recent Dutch data on the resistance ofuropathogens to the most frequently used antibiotics. The first choice for empirical antibiotic treatment in a patient with a complicated UTI is a 2nd or 3rd generation cephalosporin or the combination of amoxicillin and gentamicin. Amoxicillin-clavulanic-acid intravenously is the second empirical choice. The treatment duration must be at least 10 days. The treatment must be adjusted after the results of the urine culture become known and made more specific if possible. Oral treatment can be given if the patient's clinical situation allows it. There are separate recommendations for the treatment ofUTIs in the following patient categories: men, pre...
European Journal of Clinical Microbiology & Infectious Diseases, 2011
Due to a longstanding comprehensive &quot;search and destroy policy&quot;, methicillin-re... more Due to a longstanding comprehensive &quot;search and destroy policy&quot;, methicillin-resistant Staphylococcus aureus (MRSA) is not endemic in Western Australian (WA) acute care hospitals. As the prevalence of MRSA in the community has increased, healthcare workers (HCW) are at risk of importing MRSA into hospitals. We aimed to determine the prevalence of and risk factors for nasal MRSA colonization in our HCW population. A period prevalence study was conducted at an 850-bed tertiary hospital. Basic demographics and a nasal swab were obtained. A total of 1,542 HCWs employed in our centre were screened for MRSA, of whom 3.4% (n = 52) were colonized. MRSA colonization was more common in patient care assistants (6.8%) and nurses (5.2%) than in allied health professionals (1.7%) and doctors (0.7%) (p &lt; 0.01). Working in &quot;high-risk&quot; wards that cared for MRSA colonized/infected patients was the strongest risk factor for HCW MRSA colonization (p &lt; 0.001). ST1-IV and ST78-IV (the most common community clones in the region) were the most frequently identified clones. In conclusion, MRSA colonization of HCWs occurs primarily in HCWs caring for patients colonized or infected with MRSA. Surveillance screening of HCWs should be regularly performed on wards with patients with high MRSA colonization prevalence to prevent further spread in the hospital.
Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Her... more Reactivation 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. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLW...
We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine i... more We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virul...
Butyrate is a short-chain fatty acid (SCFA) created within the intestinal lumen by bacterial ferm... more Butyrate is a short-chain fatty acid (SCFA) created within the intestinal lumen by bacterial fermentation of largely undigested dietary carbohydrates. Its beneficial effects on cellular energy metabolism and intestinal homeostasis have garnered significant attention among SCFAs. Butyrate also has systemic effects and is known to regulate the immune system. Most of the butyrate and other SCFAs are produced in the human colon, through the fermentation of dietary fiber or resistant starch. However, the modern diet often lacks sufficient intake of fermentable dietary fiber, which can lead to low butyrate levels in the colon. To increase butyrate levels, it is helpful to incorporate fiber sources into meals and drinks that rely on slow bacterial fermentation. Butyrate is well known for its anti-inflammatory properties and has a range of immune system-related properties. As an agonist for GPR41, GPR43, or GPR109A, butyrate may have anti-inflammatory effects through these receptors’ signal...
Introduction After a large decrease in the number of cases of syphilis in the past decades, the i... more Introduction After a large decrease in the number of cases of syphilis in the past decades, the incidence of syphilis is rising again.(1) At the end of the nineties, a new epidemic of syphilis has been documented in Western-Europe and the United States.(2) Although the number of patients seems to be decreasing again, this disease is still an important infectious disease that is sexually transmitted. Many patients with newly diagnosed syphilis are also HIV-infected. These patients have a higher risk to develop neurosyphilis, an inflammation of the central nerve system. Several case reports have shown that a concurrent infection with HIV may change the natural course of neurosyphilis.(3,4,5) This might mean that patients with HIV respond different on treatment for neurosyphilis. Though, it is not known whether patients with neurosyphilis and concurrent HIV infection really respond different to treatment compared to patients without concurrent HIV-infection. But if they do, what is the...
Introduction After a large decrease in the number of cases of syphilis in the past decades, the i... more Introduction After a large decrease in the number of cases of syphilis in the past decades, the incidence of syphilis is rising again.(1) At the end of the nineties, a new epidemic of syphilis has been documented in Western-Europe and the United States.(2) Although the number of patients seems to be decreasing again, this disease is still an important infectious disease that is sexually transmitted. Many patients with newly diagnosed syphilis are also HIV-infected. These patients have a higher risk to develop neurosyphilis, an inflammation of the central nerve system. Several case reports have shown that a concurrent infection with HIV may change the natural course of neurosyphilis.(3,4,5) This might mean that patients with HIV respond different on treatment for neurosyphilis. Though, it is not known whether patients with neurosyphilis and concurrent HIV infection really respond different to treatment compared to patients without concurrent HIV-infection. But if they do, what is the...
European Journal of Clinical Microbiology & Infectious Diseases, Sep 10, 2011
Due to a longstanding comprehensive &quot;search and destroy policy&quot;, methicillin-re... more Due to a longstanding comprehensive &quot;search and destroy policy&quot;, methicillin-resistant Staphylococcus aureus (MRSA) is not endemic in Western Australian (WA) acute care hospitals. As the prevalence of MRSA in the community has increased, healthcare workers (HCW) are at risk of importing MRSA into hospitals. We aimed to determine the prevalence of and risk factors for nasal MRSA colonization in our HCW population. A period prevalence study was conducted at an 850-bed tertiary hospital. Basic demographics and a nasal swab were obtained. A total of 1,542 HCWs employed in our centre were screened for MRSA, of whom 3.4% (n = 52) were colonized. MRSA colonization was more common in patient care assistants (6.8%) and nurses (5.2%) than in allied health professionals (1.7%) and doctors (0.7%) (p &lt; 0.01). Working in &quot;high-risk&quot; wards that cared for MRSA colonized/infected patients was the strongest risk factor for HCW MRSA colonization (p &lt; 0.001). ST1-IV and ST78-IV (the most common community clones in the region) were the most frequently identified clones. In conclusion, MRSA colonization of HCWs occurs primarily in HCWs caring for patients colonized or infected with MRSA. Surveillance screening of HCWs should be regularly performed on wards with patients with high MRSA colonization prevalence to prevent further spread in the hospital.
Objectives The dolutegravir/valproic acid drug–drug interaction (DDI) is suggested to be caused b... more Objectives The dolutegravir/valproic acid drug–drug interaction (DDI) is suggested to be caused by protein displacement. Here, we assess the underlying mechanism. Methods Participants in a randomized controlled trial investigating valproic acid as an HIV latency reversing agent were recruited in a predefined pharmacokinetic substudy if they were on once-daily 50 mg dolutegravir-containing combination ART (cART) for >12 months with a plasma HIV-RNA <50 copies/mL (trial registration: ClinicalTrials.gov NCT03525730). Participants were randomized to receive 30 mg/kg/day valproic acid orally (divided into two equal doses) for 14 days or not. Total and unbound dolutegravir concentrations were measured on day 0 (before intake of valproic acid and 6 h after intake of valproic acid) and on days 1, 7, 14 and 42. Intra- and inter-subject dolutegravir concentrations and geometric means (GMs) were evaluated. Results Six of 10 participants on dolutegravir were randomized to receive valproic...
Samenvatting Infecties in het hart en de bloedbaan worden intravasale of endovasculaire infecties... more Samenvatting Infecties in het hart en de bloedbaan worden intravasale of endovasculaire infecties genoemd. De circulatie van bloed door het hart is essentieel voor de aanvoer van zuurstof en voedingstoffen naar weefsel en organen en voor de afvoer van afvalstoffen.
Nederlands tijdschrift voor geneeskunde, Jan 28, 2006
The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Poli... more The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Policy) has developed an evidence-based guideline for the empirical antimicrobial treatment of complicated urinary tract infections (UTIs) in hospitalised adult patients. The choice of treatment is based on recent Dutch data on the resistance ofuropathogens to the most frequently used antibiotics. The first choice for empirical antibiotic treatment in a patient with a complicated UTI is a 2nd or 3rd generation cephalosporin or the combination of amoxicillin and gentamicin. Amoxicillin-clavulanic-acid intravenously is the second empirical choice. The treatment duration must be at least 10 days. The treatment must be adjusted after the results of the urine culture become known and made more specific if possible. Oral treatment can be given if the patient's clinical situation allows it. There are separate recommendations for the treatment ofUTIs in the following patient categories: men, pre...
European Journal of Clinical Microbiology & Infectious Diseases, 2011
Due to a longstanding comprehensive &quot;search and destroy policy&quot;, methicillin-re... more Due to a longstanding comprehensive &quot;search and destroy policy&quot;, methicillin-resistant Staphylococcus aureus (MRSA) is not endemic in Western Australian (WA) acute care hospitals. As the prevalence of MRSA in the community has increased, healthcare workers (HCW) are at risk of importing MRSA into hospitals. We aimed to determine the prevalence of and risk factors for nasal MRSA colonization in our HCW population. A period prevalence study was conducted at an 850-bed tertiary hospital. Basic demographics and a nasal swab were obtained. A total of 1,542 HCWs employed in our centre were screened for MRSA, of whom 3.4% (n = 52) were colonized. MRSA colonization was more common in patient care assistants (6.8%) and nurses (5.2%) than in allied health professionals (1.7%) and doctors (0.7%) (p &lt; 0.01). Working in &quot;high-risk&quot; wards that cared for MRSA colonized/infected patients was the strongest risk factor for HCW MRSA colonization (p &lt; 0.001). ST1-IV and ST78-IV (the most common community clones in the region) were the most frequently identified clones. In conclusion, MRSA colonization of HCWs occurs primarily in HCWs caring for patients colonized or infected with MRSA. Surveillance screening of HCWs should be regularly performed on wards with patients with high MRSA colonization prevalence to prevent further spread in the hospital.
Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Her... more Reactivation 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. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLW...
We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine i... more We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virul...
Butyrate is a short-chain fatty acid (SCFA) created within the intestinal lumen by bacterial ferm... more Butyrate is a short-chain fatty acid (SCFA) created within the intestinal lumen by bacterial fermentation of largely undigested dietary carbohydrates. Its beneficial effects on cellular energy metabolism and intestinal homeostasis have garnered significant attention among SCFAs. Butyrate also has systemic effects and is known to regulate the immune system. Most of the butyrate and other SCFAs are produced in the human colon, through the fermentation of dietary fiber or resistant starch. However, the modern diet often lacks sufficient intake of fermentable dietary fiber, which can lead to low butyrate levels in the colon. To increase butyrate levels, it is helpful to incorporate fiber sources into meals and drinks that rely on slow bacterial fermentation. Butyrate is well known for its anti-inflammatory properties and has a range of immune system-related properties. As an agonist for GPR41, GPR43, or GPR109A, butyrate may have anti-inflammatory effects through these receptors’ signal...
Introduction After a large decrease in the number of cases of syphilis in the past decades, the i... more Introduction After a large decrease in the number of cases of syphilis in the past decades, the incidence of syphilis is rising again.(1) At the end of the nineties, a new epidemic of syphilis has been documented in Western-Europe and the United States.(2) Although the number of patients seems to be decreasing again, this disease is still an important infectious disease that is sexually transmitted. Many patients with newly diagnosed syphilis are also HIV-infected. These patients have a higher risk to develop neurosyphilis, an inflammation of the central nerve system. Several case reports have shown that a concurrent infection with HIV may change the natural course of neurosyphilis.(3,4,5) This might mean that patients with HIV respond different on treatment for neurosyphilis. Though, it is not known whether patients with neurosyphilis and concurrent HIV infection really respond different to treatment compared to patients without concurrent HIV-infection. But if they do, what is the...
Introduction After a large decrease in the number of cases of syphilis in the past decades, the i... more Introduction After a large decrease in the number of cases of syphilis in the past decades, the incidence of syphilis is rising again.(1) At the end of the nineties, a new epidemic of syphilis has been documented in Western-Europe and the United States.(2) Although the number of patients seems to be decreasing again, this disease is still an important infectious disease that is sexually transmitted. Many patients with newly diagnosed syphilis are also HIV-infected. These patients have a higher risk to develop neurosyphilis, an inflammation of the central nerve system. Several case reports have shown that a concurrent infection with HIV may change the natural course of neurosyphilis.(3,4,5) This might mean that patients with HIV respond different on treatment for neurosyphilis. Though, it is not known whether patients with neurosyphilis and concurrent HIV infection really respond different to treatment compared to patients without concurrent HIV-infection. But if they do, what is the...
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