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Papers by Anneke Dijkmans

International Journal of Infectious Diseases, Apr 1, 2014

Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general p... more Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general population. Prevention of HIV/STIs among such men could potentially reduce these infections among women-who bear the greatest HIV/STIs disease burden. HSV-2 infection has been shown to be strongly associated with HIV infections. We sought to estimate the incidence of HSV-2 infection among fishermen. Methods & Materials: Three hundred fishermen were recruited and followed-up every 3 months for 1 year. Specimen for HIV, HSV-2 serology and data on structured demographic questionnaire were collected at baseline and exit. Results: The fishermen had a mean age of 28 years and 76% were married. A significant number of men; 183 (61%) P < 0.01 and 118 (39%) P < 0.05, never used condoms with their frequent sexual partners and new sexual partners respectively. Baseline HSV-2 prevalence was 56.3% and married men were 3 times more likely to have HSV-2 infections compared to single (never married) men adjOR 3.2(95% CI; 1.8-5.5), P < 0.001. HIV positive men were twice more likely to be co-infected with HSV-2 compared to HIV negative men adjOR 2.2(95% CI; 1.2-4.2). At baseline, men who reported only one sexual partner in the last one month were less likely to have HSV-2 infections compared to those who reported multiple sexual partners for the same period adjOR 0.09(95% CI; 0.01-0.74). The annual HSV-2 incidence was 23.6%. HSV-2 negative men reporting a casual partner as their most recent sexual partner at baseline had increased risk of HSV-2 acquisition adjRR 6.7(95% CI; 2.4-18.1). Those reporting consistent condom use of over 75% at baseline had reduced risk of acquiring HSV-2 adjRR 0.12(95% CI; 0.03-0.54) P < 0.01, whereas those who reported no condom use (0% usage) had increased risk of acquiring HSV-2 adjRR 3.2(95% CI; 1.3-7.9), P < 0.01. Multiple number of sexual partners in the past 1 year was strongly associated with incident HSV-2 infection, P < 0.01. Conclusion: Fishermen comprise a young sexually-high-risk population, with high HSV-2 incidence and prevalence. Low condom use coupled with concurrent multiple sexual partnerships predispose fishermen to HSV-2 infections.

Current Opinion in Obstetrics & Gynecology, Mar 1, 2012

Parvovirus B19 infection is often considered a mild and self-limiting disease of minor clinical i... more Parvovirus B19 infection is often considered a mild and self-limiting disease of minor clinical importance. This review aims to raise awareness of recently discovered potentially devastating consequences of this infection in pregnancy, and provides updated guidelines on diagnosis and management. In contrast to previous beliefs, parvovirus B19 infection during any stage of pregnancy may not only cause fetal death, but may also result in severe and irreversible neurological sequelae in survivors. Improved diagnostic techniques allow more reliable and earlier diagnosis of fetal disease. Clinicians need to be aware of the risk of adverse outcome of parvovirus B19 infection in pregnancy, and sometimes the long interval between exposure and fetal symptoms. Accurate diagnosis using PCR and weekly ultrasound checks ups with Doppler measurement of middle cerebral artery flow velocity up to 20 weeks postexposure may improve detection of fetal disease. More timely treatment likely results in improved outcome.

PubMed, Jul 1, 2018

Background: Measurement of rifampin levels is not part of routine practice. However, low levels a... more Background: Measurement of rifampin levels is not part of routine practice. However, low levels are associated with failure of tuberculosis treatment. The clinical relevance of serum levels in daily practice is unclear. The objective was to evaluate rifampin serum concentrations and factors associated with insufficient concentrations. Methods: Patients with at least one rifampin concentration drawn 3 hours after intake (C3) between 2005 and 2014 were included. Data on demographic and clinical characteristics were collected, including side effects and dose adjustments. Two different criteria were used to define adequate concentrations (criterion 1: C3 a nd C 6 ≥ 3 mg/l; criterion 2: C3 or C6 ≥ 5 mg/l). Results: Of 63 patients, 66% and 76% had a sufficient level according to criterion 1 or 2, respectively. C3 exceeded C6 in most patients, while a late maximum was significantly associated with diabetes mellitus (p = 0.003). A dose adjustment was made in 19% of cases, more frequently in patients with insufficient levels (p = 0.02) or with ≥ 2 side effects (p = 0.03). Conclusion: Rifampin levels varied but were mostly adequate and a single measurement at 3 hours after intake provided the required information in most cases, indicating that full AUC0-24 measurements could be limited to specific situations.

PubMed, Sep 1, 2019

Background: The preferred treatment for severe methicillin-sensitive Staphylococcus aureus infect... more Background: The preferred treatment for severe methicillin-sensitive Staphylococcus aureus infections is flucloxacillin, a small-spectrum antibiotic administered intravenously (IV) and orally. However, clinicians switch to the less preferred broad-spectrum antibiotics because of the variable absorption after oral administration of flucloxacillin. A classical oral absorption test (OAT) requires overnight fasting and interruption of IV therapy, and is laborious. In the current study, we investigated whether a simplified OAT can be utilized in a clinical setting to guide antibiotic treatment in patients with severe S. aureus infections. For this, OAT IV therapy is continued and oral dosing is performed after a one-hour fast and implemented after a small study. Methods: In 196 patients receiving IV flucloxacillin by continuous infusion, a classical OAT (test A) or simplified version of the OAT (test B) was performed. In both tests, 1 g oral flucloxacillin was given and serum samples were taken prior to intake and at one and two hours after administration. Flucloxacillin concentrations were determined by high-performance liquid chromatography. Adequate absorption was defined as an increase of flucloxacillin concentration of at least 10 mg/l after one or two hours compared to baseline. Results: In a sample of 196 patients (85 F/111 M), test A was performed in 28 patients, and test B in 168 patients. Age, gender, and baseline values of creatinine and albumin were similar in both groups. The maximal increase of flucloxacillin absorption was highly variable between patients. In 26 (13%) of the 196 patients, the flucloxacillin increase did not reach the value of 10 mg/l. The median (interquartile range, IQR) maximal increase of flucloxacillin absorption was 22.0 (15-31.25) mg/l for test A and 21.5 (13-32.25) mg/l for test B. There was no significant difference in maximal increase of flucloxacillin absorption between test A and B (p = 0.74), nor between males and females (p = 0.95). Age, creatinine, and albumin were not correlated with flucloxacillin levels. Conclusions: The simplified version of the OAT is useful to identify patients with adequate oral flucloxacillin absorption, and to ensure the effective continuation of an oral small-spectrum treatment.

Antibiotics, Aug 15, 2019

Severe streptococcal infections are commonly treated with intravenous followed by oral penicillin... more Severe streptococcal infections are commonly treated with intravenous followed by oral penicillin (pheneticillin) therapy. However, switching from iv to oral therapy is complicated by the variability in oral pheneticillin absorption. We employed an Oral Absorption Test (OAT) for pheneticillin to identify patients in whom oral pheneticillin absorption is poor. Out of 84 patients 30 patients (36%) were identified as insufficient absorbers. Treatment failure due to pheneticillin malabsorption can be avoided by performing an OAT, and these patients should be treated by another antibiotic, which is known to be absorbed well.

Journal of Cardiovascular Pharmacology, Dec 1, 2011

Background: Distinct serotonin [5-hydroxytryptamine (5-HT)] receptors are involved in platelet ag... more Background: Distinct serotonin [5-hydroxytryptamine (5-HT)] receptors are involved in platelet aggregation and vasoconstriction. Compounds that simultaneously and selectively inhibit the pertaining 5-HT receptors may therefore represent a therapeutic strategy for arterial thrombosis, observed frequently after atherosclerotic plaque rupture. The vasoactive and antiplatelet effects of the combined 5-HT 1B and 5-HT 2A receptor blocker SL65.0472-00 were investigated in humans to elucidate the functional involvement of these receptors. Methods: Twenty-four volunteers, divided into 2 groups of 12, received an oral dose of 20 mg of SL65.0472-00 or placebo in a randomized, double-blind, crossover study. Pre dose and at 2, 4, and 6 hours after dosing, intra-arterial infusions of 5-HT 1B agonist sumatriptan (n = 12) or 5-HT (n = 12) were administered. Forearm blood flow (FBF) was measured using plethysmography, and platelet aggregation was measured using whole blood aggregometry induced by a combination of a threshold collagen concentration and an excess of 5-HT. Treatments were compared using analysis of variance.

Therapeutic Drug Monitoring, Aug 1, 2015

Colistin (polymyxin E) is a positively charged decapeptide antibiotic that disrupts the integrity... more Colistin (polymyxin E) is a positively charged decapeptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined.

Huisarts En Wetenschap, Mar 13, 2019

Huidpiercings zijn zelden een gezondheidsprobleem, maar piercings in kraakbeen kunnen nare gevolg... more Huidpiercings zijn zelden een gezondheidsprobleem, maar piercings in kraakbeen kunnen nare gevolgen hebben als ze ontstoken raken. Een milde ontsteking kan men het best behandelen met azijn en de piercing laten zitten. Bij ernstiger ontstekingen zijn antibiotica aan te raden.

Travel Medicine and Infectious Disease, Mar 1, 2014

We report a case of symptomatic visceral Armillifer pentastomiasis in a 23-year-old female Liberi... more We report a case of symptomatic visceral Armillifer pentastomiasis in a 23-year-old female Liberian immigrant to The Netherlands. The patient was referred to the gynecologist because of lower abdominal pain. During laparotomy, multiple adhesions were seen in the lower pelvis and a hydrosalpinx with an encapsulated Armillifer nymph, most likely Armillifer armillatus, was found. Key features of the parasite's cuticle which facilitate the diagnosis of pentastomiasis, are presented. Symptomatic pentastomiasis is uncommon, and most cases are diagnosed incidentally during surgery for other reasons, or at autopsy. With regard to increasing international migration, other imported pentastomiasis cases to Europe and North America are reviewed, and more cases are likely to be seen in the future.

Emerging Infectious Diseases, Mar 1, 2015

, caused by polycystic larvae of the tapeworm Echinococcus vogeli and unicystic larvae of E. olig... more , caused by polycystic larvae of the tapeworm Echinococcus vogeli and unicystic larvae of E. oligarthrus, is an emerging infection in rural South America (1,2). The parasites are propagated in a predator-prey cycle; the final and intermediate hosts for E. vogeli are bush dogs (Speothos venaticus) and pacas (Cuniculus paca), respectively (1,2). Human infections occur in rural areas and have been reported from several South American countries, mostly Brazil (1-3). Prompted by the recent diagnosis of an E. vogeli infection in a Surinamese patient in the Netherlands (4), we performed a retrospective analysis of all recent echinococcosis cases seen at the Amsterdam Medical Center. We describe molecular and immunohistochemical analyses from another case of E. vogeli infection. In 2009, a 48-year-old female schoolteacher from Suriname sought care at the Amsterdam Medical Center for recently increasing retrosternal pain. Born in rural Suriname, she moved to the capital city of Paramaribo at 2 years of age. She had worked in the Brokopondo District for 1 year, then worked in urban Morocco, and immigrated to the Netherlands in 1990. Physical and laboratory examination findings were unremarkable. Esophago-gastro-duodenoscopy showed no abnormality. Abdominal ultrasonography and subsequent computed tomography revealed a lesion with solid and liquid components in liver segment 4, considered consistent with a biliary cystadenoma or an echinococcal cyst. Result of an echinococcosis indirect hemagglutination test with E. granulosus hydatid fluid antigen (Fumouze, Levallois-Perret, France) was strongly positive

International Journal of Infectious Diseases, 2014

Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general p... more Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general population. Prevention of HIV/STIs among such men could potentially reduce these infections among women-who bear the greatest HIV/STIs disease burden. HSV-2 infection has been shown to be strongly associated with HIV infections. We sought to estimate the incidence of HSV-2 infection among fishermen. Methods & Materials: Three hundred fishermen were recruited and followed-up every 3 months for 1 year. Specimen for HIV, HSV-2 serology and data on structured demographic questionnaire were collected at baseline and exit. Results: The fishermen had a mean age of 28 years and 76% were married. A significant number of men; 183 (61%) P < 0.01 and 118 (39%) P < 0.05, never used condoms with their frequent sexual partners and new sexual partners respectively. Baseline HSV-2 prevalence was 56.3% and married men were 3 times more likely to have HSV-2 infections compared to single (never married) men adjOR 3.2(95% CI; 1.8-5.5), P < 0.001. HIV positive men were twice more likely to be co-infected with HSV-2 compared to HIV negative men adjOR 2.2(95% CI; 1.2-4.2). At baseline, men who reported only one sexual partner in the last one month were less likely to have HSV-2 infections compared to those who reported multiple sexual partners for the same period adjOR 0.09(95% CI; 0.01-0.74). The annual HSV-2 incidence was 23.6%. HSV-2 negative men reporting a casual partner as their most recent sexual partner at baseline had increased risk of HSV-2 acquisition adjRR 6.7(95% CI; 2.4-18.1). Those reporting consistent condom use of over 75% at baseline had reduced risk of acquiring HSV-2 adjRR 0.12(95% CI; 0.03-0.54) P < 0.01, whereas those who reported no condom use (0% usage) had increased risk of acquiring HSV-2 adjRR 3.2(95% CI; 1.3-7.9), P < 0.01. Multiple number of sexual partners in the past 1 year was strongly associated with incident HSV-2 infection, P < 0.01. Conclusion: Fishermen comprise a young sexually-high-risk population, with high HSV-2 incidence and prevalence. Low condom use coupled with concurrent multiple sexual partnerships predispose fishermen to HSV-2 infections.

Journal of Antimicrobial Chemotherapy, 2020

Objectives To evaluate the pharmacokinetics and clinical effectiveness of IV and oral fosfomycin ... more Objectives To evaluate the pharmacokinetics and clinical effectiveness of IV and oral fosfomycin treatment in patients with recurrent urinary tract infection (rUTI) with Escherichia coli. Patients and methods Patients with rUTI treated with 3 g of oral fosfomycin every 72 h for at least 14 days were included in a prospective open-label single-centre study. Serum samples were taken after oral and IV administration of fosfomycin. Urine was collected for 24 h on 3 consecutive days. Fosfomycin concentrations in serum and urine were analysed using validated LC–MS/MS. Pharmacokinetics were evaluated using a population model. EudraCT number 2018-000616-25. Results Twelve patients were included, of whom nine were also administered IV fosfomycin. Data were best described by a two-compartment model with linear elimination and a transit-absorption compartment. Median values for absolute bioavailability and serum half-life were 18% and 2.13 h, respectively. Geometric mean urine concentrations o...

Pharmacology Research & Perspectives, 2018

Fosfomycin has emerged as a potential therapy for multidrug-resistant bacterial infections. In mo... more Fosfomycin has emerged as a potential therapy for multidrug-resistant bacterial infections. In most European countries, the oral formulation is only approved as a 3 g single dose for treatment of uncomplicated cystitis. However, for the treatment of complicated systemic infections, this dose regimen is unlikely to reach efficacious serum and tissue concentrations. This study aims to investigate different fosfomycin-dosing regimens to evaluate its rationale for treatment of systemic infections. Serum concentration-time profiles of fosfomycin were simulated using a population pharmacokinetic model based on published pharmacokinetic parameter values, their uncertainty, inter-individual variability and covariates. The model was validated on published data and used to simulate a wide range of dosing regimens for oral and intravenous administration of fosfomycin. Finally, based on the minimum inhibitory concentration for E. coli, surrogate pharmacodynamic indices were calculated for each dosing regimen. This is the first population pharmacokinetic model to describe the oral pharmacokinetics of fosfomycin using data from different literature sources. The model and surrogate pharmacodynamic indices provide quantitative evidence that a dosing regimen of 6-12 g per day divided in 3 doses is required to obtain efficacious exposure and may serve as a first step in the treatment of systemic multi-drug-resistant bacterial infections.

Antibiotics, 2017

Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative acti... more Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided.

The Journal of Clinical Pharmacology, 2009

Tedisamil, a class III antiarrhythmic drug, is a P-glycoprotein substrate. Tedisamil treatment ma... more Tedisamil, a class III antiarrhythmic drug, is a P-glycoprotein substrate. Tedisamil treatment may implicate coadministration with class IV antiarrhythmics such as verapamil, a P-glycoprotein inhibitor. Pharmacokinetic and pharmacodynamic interactions between tedisamil and verapamil were evaluated in a double-blind, crossover study. Twelve healthy volunteers received a 3-day treatment of tedisamil (100 mg bid), verapamil (180 mg bid), a combination of these drugs, or placebo. Blood pressure and electrocardiograms were assessed daily and cardiac output and pharmacokinetics on day 3. Combination of tedisamil and verapamil increased tedisamil plasma concentrations (AUC(0-12 h): +77%, CI(90%): +51% to +108%; C(max): +78%, CI(90%): +57% to +102%) compared to tedisamil monotreatment but decreased plasma concentrations of verapamil (AUC(0-12 h): -21%, CI(90%): -32% to -8%; C(max): -28%, CI(90%): -39% to -14%) and norverapamil (AUC(0-12 h): -17%, CI(90%): -28% to -6%; C(max): -20%, CI(90%):-29% to -10%) compared to verapamil monotreatment. Compared to placebo, verapamil and the combination treatment increased PR by 23.5 (CI(95%): 17.9 to 29.2) ms and 12.2 (5.7 to 17.0) ms, respectively. Compared to placebo, tedisamil and the combination treatment increased QTc by 27.8 (15.8 to 39.8) ms and 45.7 (33.7 to 57.7) ms, respectively. Thus, concomitant use of tedisamil with P-glycoprotein inhibitors likely results in clinically significant drug interactions.

Nederlands Tijdschrift voor Geneeskunde, 2017

- Fosfomycin is a broad-spectrum antibiotic agent used orally for uncomplicated cystitis. The int... more - Fosfomycin is a broad-spectrum antibiotic agent used orally for uncomplicated cystitis. The intravenous form of administration has recently been authorised in the Netherlands.- Thanks to its broad spectrum and extensive tissue penetration, fosfomycin offers possibilities for the treatment of infections in different organs.- Infections with multidrug-resistant bacteria pose a significant threat to public health. Many of these multidrug-resistant bacteria are sensitive to fosfomycin, which means fosfomycin may be an option for the treatment of infections with multidrug-resistant bacteria. - There is a lack of knowledge about the pharmacological properties of fosfomycin to establish a good dosing schedule. Knowledge is also lacking about the safety of fosfomycin and the extent of its tolerability in the treatment of different infections. - More research is needed before fosfomycin can be used in the battle against multidrug-resistant bacteria.

Nederlands Tijdschrift voor Geneeskunde, 2014

Colistine werd in 1949 voor het eerst geïsoleerd uit Bacillus polymyxa var. colistinus en kwam in... more Colistine werd in 1949 voor het eerst geïsoleerd uit Bacillus polymyxa var. colistinus en kwam in 1959 op de markt. Al snel bleek dat colistine identiek was aan polymyxine E. In de jaren 60 werd veel onderzoek gedaan naar de diverse vormen van polymyxines (A tot en met E), waaronder colistine. Vanwege vermeende nefrotoxiciteit en neurotoxiciteit raakte het middel in de jaren 70 in onbruik. Tegenwoordig is colistine soms het laatste redmiddel voor ernstig zieke patiënten die lijden aan infecties met multiresistente bacteriën. Het is cruciaal dat colistine zorgvuldig wordt ingezet. In dit artikel gaan wij in op het werkingsmechanisme, de farmacologische aspecten, de indicaties en de toxiciteit van colistine.

Nederlands Tijdschrift voor Geneeskunde, 2017

Fosfomycine is een breedspectrumantibioticum dat oraal gebruikt wordt bij ongecompliceerde cystit... more Fosfomycine is een breedspectrumantibioticum dat oraal gebruikt wordt bij ongecompliceerde cystitis. Recent is de intraveneuze toedieningsvorm geregistreerd in Nederland. Door het brede spectrum en de uitgebreide weefselpenetratie biedt fosfomycine kansen om te worden ingezet bij infecties van verschillende organen. Infecties met multiresistente bacterien zijn een dreigend gevaar voor de volksgezondheid. Veel van deze multiresistente bacterien zijn gevoelig voor fosfomycine, waarmee fosfomycine een optie kan zijn in de behandeling van infecties met multiresistente bacterien. Over de farmacologische eigenschappen van fosfomycine is onvoldoende bekend om een goed doseringsschema op te kunnen stellen. Ook over de veiligheid van fosfomycine en de mate waarin dit middel verdragen wordt bij de behandeling van verschillende infecties is onvoldoende bekend. Meer onderzoek is nodig voordat fosfomycine ingezet kan worden in de strijd tegen multiresistente bacterien.

International Journal of Infectious Diseases, Apr 1, 2014

Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general p... more Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general population. Prevention of HIV/STIs among such men could potentially reduce these infections among women-who bear the greatest HIV/STIs disease burden. HSV-2 infection has been shown to be strongly associated with HIV infections. We sought to estimate the incidence of HSV-2 infection among fishermen. Methods & Materials: Three hundred fishermen were recruited and followed-up every 3 months for 1 year. Specimen for HIV, HSV-2 serology and data on structured demographic questionnaire were collected at baseline and exit. Results: The fishermen had a mean age of 28 years and 76% were married. A significant number of men; 183 (61%) P < 0.01 and 118 (39%) P < 0.05, never used condoms with their frequent sexual partners and new sexual partners respectively. Baseline HSV-2 prevalence was 56.3% and married men were 3 times more likely to have HSV-2 infections compared to single (never married) men adjOR 3.2(95% CI; 1.8-5.5), P < 0.001. HIV positive men were twice more likely to be co-infected with HSV-2 compared to HIV negative men adjOR 2.2(95% CI; 1.2-4.2). At baseline, men who reported only one sexual partner in the last one month were less likely to have HSV-2 infections compared to those who reported multiple sexual partners for the same period adjOR 0.09(95% CI; 0.01-0.74). The annual HSV-2 incidence was 23.6%. HSV-2 negative men reporting a casual partner as their most recent sexual partner at baseline had increased risk of HSV-2 acquisition adjRR 6.7(95% CI; 2.4-18.1). Those reporting consistent condom use of over 75% at baseline had reduced risk of acquiring HSV-2 adjRR 0.12(95% CI; 0.03-0.54) P < 0.01, whereas those who reported no condom use (0% usage) had increased risk of acquiring HSV-2 adjRR 3.2(95% CI; 1.3-7.9), P < 0.01. Multiple number of sexual partners in the past 1 year was strongly associated with incident HSV-2 infection, P < 0.01. Conclusion: Fishermen comprise a young sexually-high-risk population, with high HSV-2 incidence and prevalence. Low condom use coupled with concurrent multiple sexual partnerships predispose fishermen to HSV-2 infections.

Current Opinion in Obstetrics & Gynecology, Mar 1, 2012

Parvovirus B19 infection is often considered a mild and self-limiting disease of minor clinical i... more Parvovirus B19 infection is often considered a mild and self-limiting disease of minor clinical importance. This review aims to raise awareness of recently discovered potentially devastating consequences of this infection in pregnancy, and provides updated guidelines on diagnosis and management. In contrast to previous beliefs, parvovirus B19 infection during any stage of pregnancy may not only cause fetal death, but may also result in severe and irreversible neurological sequelae in survivors. Improved diagnostic techniques allow more reliable and earlier diagnosis of fetal disease. Clinicians need to be aware of the risk of adverse outcome of parvovirus B19 infection in pregnancy, and sometimes the long interval between exposure and fetal symptoms. Accurate diagnosis using PCR and weekly ultrasound checks ups with Doppler measurement of middle cerebral artery flow velocity up to 20 weeks postexposure may improve detection of fetal disease. More timely treatment likely results in improved outcome.

PubMed, Jul 1, 2018

Background: Measurement of rifampin levels is not part of routine practice. However, low levels a... more Background: Measurement of rifampin levels is not part of routine practice. However, low levels are associated with failure of tuberculosis treatment. The clinical relevance of serum levels in daily practice is unclear. The objective was to evaluate rifampin serum concentrations and factors associated with insufficient concentrations. Methods: Patients with at least one rifampin concentration drawn 3 hours after intake (C3) between 2005 and 2014 were included. Data on demographic and clinical characteristics were collected, including side effects and dose adjustments. Two different criteria were used to define adequate concentrations (criterion 1: C3 a nd C 6 ≥ 3 mg/l; criterion 2: C3 or C6 ≥ 5 mg/l). Results: Of 63 patients, 66% and 76% had a sufficient level according to criterion 1 or 2, respectively. C3 exceeded C6 in most patients, while a late maximum was significantly associated with diabetes mellitus (p = 0.003). A dose adjustment was made in 19% of cases, more frequently in patients with insufficient levels (p = 0.02) or with ≥ 2 side effects (p = 0.03). Conclusion: Rifampin levels varied but were mostly adequate and a single measurement at 3 hours after intake provided the required information in most cases, indicating that full AUC0-24 measurements could be limited to specific situations.

PubMed, Sep 1, 2019

Background: The preferred treatment for severe methicillin-sensitive Staphylococcus aureus infect... more Background: The preferred treatment for severe methicillin-sensitive Staphylococcus aureus infections is flucloxacillin, a small-spectrum antibiotic administered intravenously (IV) and orally. However, clinicians switch to the less preferred broad-spectrum antibiotics because of the variable absorption after oral administration of flucloxacillin. A classical oral absorption test (OAT) requires overnight fasting and interruption of IV therapy, and is laborious. In the current study, we investigated whether a simplified OAT can be utilized in a clinical setting to guide antibiotic treatment in patients with severe S. aureus infections. For this, OAT IV therapy is continued and oral dosing is performed after a one-hour fast and implemented after a small study. Methods: In 196 patients receiving IV flucloxacillin by continuous infusion, a classical OAT (test A) or simplified version of the OAT (test B) was performed. In both tests, 1 g oral flucloxacillin was given and serum samples were taken prior to intake and at one and two hours after administration. Flucloxacillin concentrations were determined by high-performance liquid chromatography. Adequate absorption was defined as an increase of flucloxacillin concentration of at least 10 mg/l after one or two hours compared to baseline. Results: In a sample of 196 patients (85 F/111 M), test A was performed in 28 patients, and test B in 168 patients. Age, gender, and baseline values of creatinine and albumin were similar in both groups. The maximal increase of flucloxacillin absorption was highly variable between patients. In 26 (13%) of the 196 patients, the flucloxacillin increase did not reach the value of 10 mg/l. The median (interquartile range, IQR) maximal increase of flucloxacillin absorption was 22.0 (15-31.25) mg/l for test A and 21.5 (13-32.25) mg/l for test B. There was no significant difference in maximal increase of flucloxacillin absorption between test A and B (p = 0.74), nor between males and females (p = 0.95). Age, creatinine, and albumin were not correlated with flucloxacillin levels. Conclusions: The simplified version of the OAT is useful to identify patients with adequate oral flucloxacillin absorption, and to ensure the effective continuation of an oral small-spectrum treatment.

Antibiotics, Aug 15, 2019

Severe streptococcal infections are commonly treated with intravenous followed by oral penicillin... more Severe streptococcal infections are commonly treated with intravenous followed by oral penicillin (pheneticillin) therapy. However, switching from iv to oral therapy is complicated by the variability in oral pheneticillin absorption. We employed an Oral Absorption Test (OAT) for pheneticillin to identify patients in whom oral pheneticillin absorption is poor. Out of 84 patients 30 patients (36%) were identified as insufficient absorbers. Treatment failure due to pheneticillin malabsorption can be avoided by performing an OAT, and these patients should be treated by another antibiotic, which is known to be absorbed well.

Journal of Cardiovascular Pharmacology, Dec 1, 2011

Background: Distinct serotonin [5-hydroxytryptamine (5-HT)] receptors are involved in platelet ag... more Background: Distinct serotonin [5-hydroxytryptamine (5-HT)] receptors are involved in platelet aggregation and vasoconstriction. Compounds that simultaneously and selectively inhibit the pertaining 5-HT receptors may therefore represent a therapeutic strategy for arterial thrombosis, observed frequently after atherosclerotic plaque rupture. The vasoactive and antiplatelet effects of the combined 5-HT 1B and 5-HT 2A receptor blocker SL65.0472-00 were investigated in humans to elucidate the functional involvement of these receptors. Methods: Twenty-four volunteers, divided into 2 groups of 12, received an oral dose of 20 mg of SL65.0472-00 or placebo in a randomized, double-blind, crossover study. Pre dose and at 2, 4, and 6 hours after dosing, intra-arterial infusions of 5-HT 1B agonist sumatriptan (n = 12) or 5-HT (n = 12) were administered. Forearm blood flow (FBF) was measured using plethysmography, and platelet aggregation was measured using whole blood aggregometry induced by a combination of a threshold collagen concentration and an excess of 5-HT. Treatments were compared using analysis of variance.

Therapeutic Drug Monitoring, Aug 1, 2015

Colistin (polymyxin E) is a positively charged decapeptide antibiotic that disrupts the integrity... more Colistin (polymyxin E) is a positively charged decapeptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simultaneously inhibited. Colistin is increasingly being prescribed as rescue treatment for infections with multidrug-resistant bacilli. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic colistin therapy, and have severely limited its application in the past. However, these side effects are largely reversible and can be managed through close monitoring. The prodrug colistimethate sodium (CMS) is less toxic and is, therefore, the preferred formulation for parenteral administration. Importantly, resistance to colistin seems to emerge often unless it is combined with another antibiotic, but further studies into this phenomenon are necessary. Pharmacokinetic and pharmacodynamic properties have received little attention, partly because of the physicochemical peculiarities of polymyxin antibiotics, especially their propensity to stick to other molecules and surfaces. The ratio between the area under the curve of free colistin and the pathogen's Minimal Inhibitory Concentration (MIC) best predicts microbiological and clinical responses, but more studies are needed in this area. Likewise, further standardization is needed in production and labeling of colistin formulations, and in the way the susceptibility of bacteria to colistin is determined.

Huisarts En Wetenschap, Mar 13, 2019

Huidpiercings zijn zelden een gezondheidsprobleem, maar piercings in kraakbeen kunnen nare gevolg... more Huidpiercings zijn zelden een gezondheidsprobleem, maar piercings in kraakbeen kunnen nare gevolgen hebben als ze ontstoken raken. Een milde ontsteking kan men het best behandelen met azijn en de piercing laten zitten. Bij ernstiger ontstekingen zijn antibiotica aan te raden.

Travel Medicine and Infectious Disease, Mar 1, 2014

We report a case of symptomatic visceral Armillifer pentastomiasis in a 23-year-old female Liberi... more We report a case of symptomatic visceral Armillifer pentastomiasis in a 23-year-old female Liberian immigrant to The Netherlands. The patient was referred to the gynecologist because of lower abdominal pain. During laparotomy, multiple adhesions were seen in the lower pelvis and a hydrosalpinx with an encapsulated Armillifer nymph, most likely Armillifer armillatus, was found. Key features of the parasite's cuticle which facilitate the diagnosis of pentastomiasis, are presented. Symptomatic pentastomiasis is uncommon, and most cases are diagnosed incidentally during surgery for other reasons, or at autopsy. With regard to increasing international migration, other imported pentastomiasis cases to Europe and North America are reviewed, and more cases are likely to be seen in the future.

Emerging Infectious Diseases, Mar 1, 2015

, caused by polycystic larvae of the tapeworm Echinococcus vogeli and unicystic larvae of E. olig... more , caused by polycystic larvae of the tapeworm Echinococcus vogeli and unicystic larvae of E. oligarthrus, is an emerging infection in rural South America (1,2). The parasites are propagated in a predator-prey cycle; the final and intermediate hosts for E. vogeli are bush dogs (Speothos venaticus) and pacas (Cuniculus paca), respectively (1,2). Human infections occur in rural areas and have been reported from several South American countries, mostly Brazil (1-3). Prompted by the recent diagnosis of an E. vogeli infection in a Surinamese patient in the Netherlands (4), we performed a retrospective analysis of all recent echinococcosis cases seen at the Amsterdam Medical Center. We describe molecular and immunohistochemical analyses from another case of E. vogeli infection. In 2009, a 48-year-old female schoolteacher from Suriname sought care at the Amsterdam Medical Center for recently increasing retrosternal pain. Born in rural Suriname, she moved to the capital city of Paramaribo at 2 years of age. She had worked in the Brokopondo District for 1 year, then worked in urban Morocco, and immigrated to the Netherlands in 1990. Physical and laboratory examination findings were unremarkable. Esophago-gastro-duodenoscopy showed no abnormality. Abdominal ultrasonography and subsequent computed tomography revealed a lesion with solid and liquid components in liver segment 4, considered consistent with a biliary cystadenoma or an echinococcal cyst. Result of an echinococcosis indirect hemagglutination test with E. granulosus hydatid fluid antigen (Fumouze, Levallois-Perret, France) was strongly positive

International Journal of Infectious Diseases, 2014

Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general p... more Background: Men with high-risk sexual behavior are important drivers of HIV/STIs in the general population. Prevention of HIV/STIs among such men could potentially reduce these infections among women-who bear the greatest HIV/STIs disease burden. HSV-2 infection has been shown to be strongly associated with HIV infections. We sought to estimate the incidence of HSV-2 infection among fishermen. Methods & Materials: Three hundred fishermen were recruited and followed-up every 3 months for 1 year. Specimen for HIV, HSV-2 serology and data on structured demographic questionnaire were collected at baseline and exit. Results: The fishermen had a mean age of 28 years and 76% were married. A significant number of men; 183 (61%) P < 0.01 and 118 (39%) P < 0.05, never used condoms with their frequent sexual partners and new sexual partners respectively. Baseline HSV-2 prevalence was 56.3% and married men were 3 times more likely to have HSV-2 infections compared to single (never married) men adjOR 3.2(95% CI; 1.8-5.5), P < 0.001. HIV positive men were twice more likely to be co-infected with HSV-2 compared to HIV negative men adjOR 2.2(95% CI; 1.2-4.2). At baseline, men who reported only one sexual partner in the last one month were less likely to have HSV-2 infections compared to those who reported multiple sexual partners for the same period adjOR 0.09(95% CI; 0.01-0.74). The annual HSV-2 incidence was 23.6%. HSV-2 negative men reporting a casual partner as their most recent sexual partner at baseline had increased risk of HSV-2 acquisition adjRR 6.7(95% CI; 2.4-18.1). Those reporting consistent condom use of over 75% at baseline had reduced risk of acquiring HSV-2 adjRR 0.12(95% CI; 0.03-0.54) P < 0.01, whereas those who reported no condom use (0% usage) had increased risk of acquiring HSV-2 adjRR 3.2(95% CI; 1.3-7.9), P < 0.01. Multiple number of sexual partners in the past 1 year was strongly associated with incident HSV-2 infection, P < 0.01. Conclusion: Fishermen comprise a young sexually-high-risk population, with high HSV-2 incidence and prevalence. Low condom use coupled with concurrent multiple sexual partnerships predispose fishermen to HSV-2 infections.

Journal of Antimicrobial Chemotherapy, 2020

Objectives To evaluate the pharmacokinetics and clinical effectiveness of IV and oral fosfomycin ... more Objectives To evaluate the pharmacokinetics and clinical effectiveness of IV and oral fosfomycin treatment in patients with recurrent urinary tract infection (rUTI) with Escherichia coli. Patients and methods Patients with rUTI treated with 3 g of oral fosfomycin every 72 h for at least 14 days were included in a prospective open-label single-centre study. Serum samples were taken after oral and IV administration of fosfomycin. Urine was collected for 24 h on 3 consecutive days. Fosfomycin concentrations in serum and urine were analysed using validated LC–MS/MS. Pharmacokinetics were evaluated using a population model. EudraCT number 2018-000616-25. Results Twelve patients were included, of whom nine were also administered IV fosfomycin. Data were best described by a two-compartment model with linear elimination and a transit-absorption compartment. Median values for absolute bioavailability and serum half-life were 18% and 2.13 h, respectively. Geometric mean urine concentrations o...

Pharmacology Research & Perspectives, 2018

Fosfomycin has emerged as a potential therapy for multidrug-resistant bacterial infections. In mo... more Fosfomycin has emerged as a potential therapy for multidrug-resistant bacterial infections. In most European countries, the oral formulation is only approved as a 3 g single dose for treatment of uncomplicated cystitis. However, for the treatment of complicated systemic infections, this dose regimen is unlikely to reach efficacious serum and tissue concentrations. This study aims to investigate different fosfomycin-dosing regimens to evaluate its rationale for treatment of systemic infections. Serum concentration-time profiles of fosfomycin were simulated using a population pharmacokinetic model based on published pharmacokinetic parameter values, their uncertainty, inter-individual variability and covariates. The model was validated on published data and used to simulate a wide range of dosing regimens for oral and intravenous administration of fosfomycin. Finally, based on the minimum inhibitory concentration for E. coli, surrogate pharmacodynamic indices were calculated for each dosing regimen. This is the first population pharmacokinetic model to describe the oral pharmacokinetics of fosfomycin using data from different literature sources. The model and surrogate pharmacodynamic indices provide quantitative evidence that a dosing regimen of 6-12 g per day divided in 3 doses is required to obtain efficacious exposure and may serve as a first step in the treatment of systemic multi-drug-resistant bacterial infections.

Antibiotics, 2017

Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative acti... more Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided.

The Journal of Clinical Pharmacology, 2009

Tedisamil, a class III antiarrhythmic drug, is a P-glycoprotein substrate. Tedisamil treatment ma... more Tedisamil, a class III antiarrhythmic drug, is a P-glycoprotein substrate. Tedisamil treatment may implicate coadministration with class IV antiarrhythmics such as verapamil, a P-glycoprotein inhibitor. Pharmacokinetic and pharmacodynamic interactions between tedisamil and verapamil were evaluated in a double-blind, crossover study. Twelve healthy volunteers received a 3-day treatment of tedisamil (100 mg bid), verapamil (180 mg bid), a combination of these drugs, or placebo. Blood pressure and electrocardiograms were assessed daily and cardiac output and pharmacokinetics on day 3. Combination of tedisamil and verapamil increased tedisamil plasma concentrations (AUC(0-12 h): +77%, CI(90%): +51% to +108%; C(max): +78%, CI(90%): +57% to +102%) compared to tedisamil monotreatment but decreased plasma concentrations of verapamil (AUC(0-12 h): -21%, CI(90%): -32% to -8%; C(max): -28%, CI(90%): -39% to -14%) and norverapamil (AUC(0-12 h): -17%, CI(90%): -28% to -6%; C(max): -20%, CI(90%):-29% to -10%) compared to verapamil monotreatment. Compared to placebo, verapamil and the combination treatment increased PR by 23.5 (CI(95%): 17.9 to 29.2) ms and 12.2 (5.7 to 17.0) ms, respectively. Compared to placebo, tedisamil and the combination treatment increased QTc by 27.8 (15.8 to 39.8) ms and 45.7 (33.7 to 57.7) ms, respectively. Thus, concomitant use of tedisamil with P-glycoprotein inhibitors likely results in clinically significant drug interactions.

Nederlands Tijdschrift voor Geneeskunde, 2017

- Fosfomycin is a broad-spectrum antibiotic agent used orally for uncomplicated cystitis. The int... more - Fosfomycin is a broad-spectrum antibiotic agent used orally for uncomplicated cystitis. The intravenous form of administration has recently been authorised in the Netherlands.- Thanks to its broad spectrum and extensive tissue penetration, fosfomycin offers possibilities for the treatment of infections in different organs.- Infections with multidrug-resistant bacteria pose a significant threat to public health. Many of these multidrug-resistant bacteria are sensitive to fosfomycin, which means fosfomycin may be an option for the treatment of infections with multidrug-resistant bacteria. - There is a lack of knowledge about the pharmacological properties of fosfomycin to establish a good dosing schedule. Knowledge is also lacking about the safety of fosfomycin and the extent of its tolerability in the treatment of different infections. - More research is needed before fosfomycin can be used in the battle against multidrug-resistant bacteria.

Nederlands Tijdschrift voor Geneeskunde, 2014

Colistine werd in 1949 voor het eerst geïsoleerd uit Bacillus polymyxa var. colistinus en kwam in... more Colistine werd in 1949 voor het eerst geïsoleerd uit Bacillus polymyxa var. colistinus en kwam in 1959 op de markt. Al snel bleek dat colistine identiek was aan polymyxine E. In de jaren 60 werd veel onderzoek gedaan naar de diverse vormen van polymyxines (A tot en met E), waaronder colistine. Vanwege vermeende nefrotoxiciteit en neurotoxiciteit raakte het middel in de jaren 70 in onbruik. Tegenwoordig is colistine soms het laatste redmiddel voor ernstig zieke patiënten die lijden aan infecties met multiresistente bacteriën. Het is cruciaal dat colistine zorgvuldig wordt ingezet. In dit artikel gaan wij in op het werkingsmechanisme, de farmacologische aspecten, de indicaties en de toxiciteit van colistine.

Nederlands Tijdschrift voor Geneeskunde, 2017

Fosfomycine is een breedspectrumantibioticum dat oraal gebruikt wordt bij ongecompliceerde cystit... more Fosfomycine is een breedspectrumantibioticum dat oraal gebruikt wordt bij ongecompliceerde cystitis. Recent is de intraveneuze toedieningsvorm geregistreerd in Nederland. Door het brede spectrum en de uitgebreide weefselpenetratie biedt fosfomycine kansen om te worden ingezet bij infecties van verschillende organen. Infecties met multiresistente bacterien zijn een dreigend gevaar voor de volksgezondheid. Veel van deze multiresistente bacterien zijn gevoelig voor fosfomycine, waarmee fosfomycine een optie kan zijn in de behandeling van infecties met multiresistente bacterien. Over de farmacologische eigenschappen van fosfomycine is onvoldoende bekend om een goed doseringsschema op te kunnen stellen. Ook over de veiligheid van fosfomycine en de mate waarin dit middel verdragen wordt bij de behandeling van verschillende infecties is onvoldoende bekend. Meer onderzoek is nodig voordat fosfomycine ingezet kan worden in de strijd tegen multiresistente bacterien.