Jan Verhaegen - Academia.edu (original) (raw)
Papers by Jan Verhaegen
Pediatric Infectious Disease Journal, 2013
Journal of Clinical Pathology, 1998
Journal of Clinical Microbiology, 2002
Journal of Clinical Microbiology, 2001
UF-100 flow cytometer and urine strip results were cross-interpreted to predict culture outcomes.... more UF-100 flow cytometer and urine strip results were cross-interpreted to predict culture outcomes. The best negative predictive value was obtained with bacteria at ≥1,000/μl, white blood cells at ≥20/μl, or leukocyte esterase positivity. Nine of 24 false negatives were clinically significant. Thus, UF-100 and urine strip results do not accurately predict the outcome of cultures.
Acta clinica Belgica, 1998
Vaccine, Jan 2, 2018
In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007-201... more In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007-2011) to PCV13 (2011-2015) and to PCV10 (2015-2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance. Two infant populations aged 6-30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed. Culture-based (DCC: 462/760; 60.8% - AOM: 27/39;...
Antimicrobial agents and chemotherapy, Jan 8, 2015
The unbound drug hypothesis states that only unbound drug concentrations are active and available... more The unbound drug hypothesis states that only unbound drug concentrations are active and available for clearance and highly variable results regarding unbound vancomycin fractions are reported in literature. We determined unbound vancomycin fractions in four different patient groups using a Liquid Chromatography Mass Spectrometry (LC-MS/MS) method and identified factors that modulate vancomycin binding. We further developed and validated a prediction model to estimate unbound vancomycin concentrations. Vancomycin (unbound and total) concentrations were measured in 90 patients from 4 different patient wards (hematology (n=33 samples); intensive care unit (ICU) (n=51); orthopedic (n=44) and pediatrics (6 months to 14 years, n=18)) using a validated LC-MS/MS method. Multiple linear mixed model analysis was performed to identify patient variables that were predictive for unbound vancomycin fractions and concentrations. Variables included in the model were age, patient ward, number of co5...
Infection Control and Hospital Epidemiology, 2002
The European respiratory journal, 2006
Four separate categories of chronic Pseudomonas aeruginosa (Pa) infection in children with cystic... more Four separate categories of chronic Pseudomonas aeruginosa (Pa) infection in children with cystic fibrosis (CF) have been previously defined, based on airway cultures taken over the previous year. The aim of the present study was to evaluate this definition in the current authors' paediatric and adult CF clinic using clinical, immunological and lung function parameters. During follow-up, out of 193 patients, 55 (34%) CF patients had never been infected with Pa, 27 (17%) were free of Pa, 29 (18%) were intermittently infected and 51 (31%) were chronically infected. Disease severity markers, such as lung function, were significantly worse in the chronic group, especially in the paediatric population. Differences in adult patients were smaller and no longer significant. Pa antibodies differed strongly between the groups, and were very high (mean+/-sd 55.4+/-5.5) and highly statistically significant from all other groups in the chronic group. They were low and different from all othe...
Clinica Chimica Acta, 2015
Accurate quantification of vancomycin in plasma is important for adequate dose-adjustment. As lit... more Accurate quantification of vancomycin in plasma is important for adequate dose-adjustment. As literature suggests between-method differences, our first objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for total vancomycin in human plasma and to compare frequently used immunoassays with this method. Secondly, we investigated the clinical impact of between-method quantification differences. For LC-MS/MS, lithium heparin plasma was extracted by adding a precipitation reagent containing the internal standard (vancomycin-des-leucine). Analysis was performed on an Acquity TQD mass spectrometer equipped with an Acquity UPLC 2795 separations module. Our method was analytically validated and compared with four frequently used immunoassays from four different manufacturers. Vancomycin concentrations were clinically classified as toxic, therapeutic and sub-therapeutic. Clinical discordance was calculated using LC-MS/MS as a reference. A novel LC-MS/MS method using protein precipitation as sole pretreatment and an analysis time of 5.0 min was developed. The assay had a total imprecision of 2.6-8.5%, a limit of quantification of 0.3 mg/L and an accuracy ranging from 101.4 to 111.2%. Using LC-MS/MS as reference, three immunoassays showed a mean proportional difference within 10% and one showed a substantial mean proportional difference of >20%. Clinical discordant interpretation of the obtained concentrations ranged from 6.1 to 22.2%. We developed a novel LC-MS/MS method for rapid analysis of total vancomycin concentrations in human plasma. Correlation of the method with immunoassays showed a mean proportional difference >20% for one of the assays, causing discordant clinical interpretation in more than 1 out of 5 samples.
Journal of clinical microbiology, 1999
Efforts to improve the diagnosis of invasive aspergillosis (IA) have been directed towards the de... more Efforts to improve the diagnosis of invasive aspergillosis (IA) have been directed towards the detection of fungal antigens, including galactomannan (GM). However, previous evaluations of GM detection have been hampered by a lack of proven cases of IA and by a nonserial study design. This prospective study assessed the diagnostic value of serial screening for circulating GM by using a recently developed sandwich enzyme-linked immunosorbent assay (ELISA) for prolonged-neutropenic and/or steroid-treated patients with hematological disorders. Serum GM levels were monitored twice weekly for 186 consecutive patients at increased risk for IA. The patients were stratified according to the likelihood of IA (proven, probable, possible, and no evidence of IA) by using stringent criteria. Proven IA was defined by characteristic histopathological findings together with a positive culture for Aspergillus species. Autopsy and culture from autopsy specimens was used to verify both positive and neg...
Journal of clinical microbiology, 1998
Four identification tests, proposed in addition to conventional methods, were evaluated with 320 ... more Four identification tests, proposed in addition to conventional methods, were evaluated with 320 fermentative nonlipophilic Corynebacterium strains: growth at 20 degrees C, glucose fermentation at 42 degrees C, alkalinization of sodium formate, and acid production from ethylene glycol. These tests were highly discriminant. Corynebacterium amycolatum displayed a unique profile, allowing it to be distinguished from similar species, such as C. xerosis, C. striatum, and C. minutissimum.
Journal of clinical microbiology, 1995
A total of 505 fermentative and 201 nonfermentative gram-negative bacilli, identified by conventi... more A total of 505 fermentative and 201 nonfermentative gram-negative bacilli, identified by conventional methods, were tested by the Crystal Enteric/Non-Fermenter ID kit and by the API 20E or API 20NE identification system. The overall correct results for fermenters were 92.9% by the Crystal kit and 89.1% by the API 20E system. The false identifications (genus and species incorrect) accounted for 3.1 and 7.1% for the Crystal and API systems, respectively. For nonfermenters, figures for correct identifications by the two systems were comparable (Crystal, 75.9%; API 20NE, 75.3%) while the API 20NE system gave twice as many incorrect results (13.8%) as Crystal (6.3%); however, Crystal failed to precisely identify several species included in a "miscellaneous" group. The Crystal Enteric/Non-Fermenter system is an easy-to-use kit which compares favorably with other commercial systems.
Mayo Clinic Proceedings, 2007
To investigate the risk factors for Staphylococcus aureus infective endocarditis (SAIE) and 6-mon... more To investigate the risk factors for Staphylococcus aureus infective endocarditis (SAIE) and 6-month mortality in patients with S aureus bacteremia (SAB). This study consisted of patients who were diagnosed as having nosocomial or community-acquired SAB or SAIE between June 1, 2000, and December 31, 2005. Clinical characteristics of patients with SAB were compared with those of patients with SAIE, and predictors of mortality in patients with SAB were analyzed. The median age of the 132 randomly selected patients with SAB and the 66 patients with SAIE was 66 and 68 years, respectively. Univariable analysis showed that unknown origin of SAB, a valvular prosthesis, a pacemaker, persistent fever, and persistent bacteremia were significantly associated with SAIE. In multivariable analysis, unknown origin of SAB (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.9-9.3; P=.001), a valvular prosthesis (OR, 9.2; 95% CI, 3.2-26.2; P<.001), persistent fever (OR, 3.1; 95% CI, 1.0-9.0; P=.04), and persistent bacteremia (OR, 6.8; 95% CI, 2.3-20.2- P=.001) were independently associated with SAIE. Six- month mortality was 8% in patients with SAB vs 35% in patients with SAIE (OR, 6.5; 95% CI, 2.9- 14.8; P<.001). In univariable analysis, methicillin- resistant S aureus (OR, 7.2; 95% CI, 1.7 - 29.4; P=.005) was significantly associated with 6-month mortality in patients with SAB. Unknown origin of SAB, a valvular prosthesis, persistent fever, and persistent bacteremia were independently associated with SAIE in patients with SAB. In univariable analysis, methicillin-resistant S aureus was associated with 6-month mortality in patients with SAB. S aureus infective endocarditis had a significantly higher mortality than SAB. The optimal management of SAB and SAIE deserves further study.
Clinical Microbiology Newsletter, 1997
Journal of Clinical Microbiology, 2014
Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-T... more Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDRsl and is thus falsely scored as resistance. Our findings suggest that MTBDRsl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.
Pediatric Infectious Disease Journal, 2013
Journal of Clinical Pathology, 1998
Journal of Clinical Microbiology, 2002
Journal of Clinical Microbiology, 2001
UF-100 flow cytometer and urine strip results were cross-interpreted to predict culture outcomes.... more UF-100 flow cytometer and urine strip results were cross-interpreted to predict culture outcomes. The best negative predictive value was obtained with bacteria at ≥1,000/μl, white blood cells at ≥20/μl, or leukocyte esterase positivity. Nine of 24 false negatives were clinically significant. Thus, UF-100 and urine strip results do not accurately predict the outcome of cultures.
Acta clinica Belgica, 1998
Vaccine, Jan 2, 2018
In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007-201... more In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007-2011) to PCV13 (2011-2015) and to PCV10 (2015-2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance. Two infant populations aged 6-30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed. Culture-based (DCC: 462/760; 60.8% - AOM: 27/39;...
Antimicrobial agents and chemotherapy, Jan 8, 2015
The unbound drug hypothesis states that only unbound drug concentrations are active and available... more The unbound drug hypothesis states that only unbound drug concentrations are active and available for clearance and highly variable results regarding unbound vancomycin fractions are reported in literature. We determined unbound vancomycin fractions in four different patient groups using a Liquid Chromatography Mass Spectrometry (LC-MS/MS) method and identified factors that modulate vancomycin binding. We further developed and validated a prediction model to estimate unbound vancomycin concentrations. Vancomycin (unbound and total) concentrations were measured in 90 patients from 4 different patient wards (hematology (n=33 samples); intensive care unit (ICU) (n=51); orthopedic (n=44) and pediatrics (6 months to 14 years, n=18)) using a validated LC-MS/MS method. Multiple linear mixed model analysis was performed to identify patient variables that were predictive for unbound vancomycin fractions and concentrations. Variables included in the model were age, patient ward, number of co5...
Infection Control and Hospital Epidemiology, 2002
The European respiratory journal, 2006
Four separate categories of chronic Pseudomonas aeruginosa (Pa) infection in children with cystic... more Four separate categories of chronic Pseudomonas aeruginosa (Pa) infection in children with cystic fibrosis (CF) have been previously defined, based on airway cultures taken over the previous year. The aim of the present study was to evaluate this definition in the current authors' paediatric and adult CF clinic using clinical, immunological and lung function parameters. During follow-up, out of 193 patients, 55 (34%) CF patients had never been infected with Pa, 27 (17%) were free of Pa, 29 (18%) were intermittently infected and 51 (31%) were chronically infected. Disease severity markers, such as lung function, were significantly worse in the chronic group, especially in the paediatric population. Differences in adult patients were smaller and no longer significant. Pa antibodies differed strongly between the groups, and were very high (mean+/-sd 55.4+/-5.5) and highly statistically significant from all other groups in the chronic group. They were low and different from all othe...
Clinica Chimica Acta, 2015
Accurate quantification of vancomycin in plasma is important for adequate dose-adjustment. As lit... more Accurate quantification of vancomycin in plasma is important for adequate dose-adjustment. As literature suggests between-method differences, our first objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for total vancomycin in human plasma and to compare frequently used immunoassays with this method. Secondly, we investigated the clinical impact of between-method quantification differences. For LC-MS/MS, lithium heparin plasma was extracted by adding a precipitation reagent containing the internal standard (vancomycin-des-leucine). Analysis was performed on an Acquity TQD mass spectrometer equipped with an Acquity UPLC 2795 separations module. Our method was analytically validated and compared with four frequently used immunoassays from four different manufacturers. Vancomycin concentrations were clinically classified as toxic, therapeutic and sub-therapeutic. Clinical discordance was calculated using LC-MS/MS as a reference. A novel LC-MS/MS method using protein precipitation as sole pretreatment and an analysis time of 5.0 min was developed. The assay had a total imprecision of 2.6-8.5%, a limit of quantification of 0.3 mg/L and an accuracy ranging from 101.4 to 111.2%. Using LC-MS/MS as reference, three immunoassays showed a mean proportional difference within 10% and one showed a substantial mean proportional difference of >20%. Clinical discordant interpretation of the obtained concentrations ranged from 6.1 to 22.2%. We developed a novel LC-MS/MS method for rapid analysis of total vancomycin concentrations in human plasma. Correlation of the method with immunoassays showed a mean proportional difference >20% for one of the assays, causing discordant clinical interpretation in more than 1 out of 5 samples.
Journal of clinical microbiology, 1999
Efforts to improve the diagnosis of invasive aspergillosis (IA) have been directed towards the de... more Efforts to improve the diagnosis of invasive aspergillosis (IA) have been directed towards the detection of fungal antigens, including galactomannan (GM). However, previous evaluations of GM detection have been hampered by a lack of proven cases of IA and by a nonserial study design. This prospective study assessed the diagnostic value of serial screening for circulating GM by using a recently developed sandwich enzyme-linked immunosorbent assay (ELISA) for prolonged-neutropenic and/or steroid-treated patients with hematological disorders. Serum GM levels were monitored twice weekly for 186 consecutive patients at increased risk for IA. The patients were stratified according to the likelihood of IA (proven, probable, possible, and no evidence of IA) by using stringent criteria. Proven IA was defined by characteristic histopathological findings together with a positive culture for Aspergillus species. Autopsy and culture from autopsy specimens was used to verify both positive and neg...
Journal of clinical microbiology, 1998
Four identification tests, proposed in addition to conventional methods, were evaluated with 320 ... more Four identification tests, proposed in addition to conventional methods, were evaluated with 320 fermentative nonlipophilic Corynebacterium strains: growth at 20 degrees C, glucose fermentation at 42 degrees C, alkalinization of sodium formate, and acid production from ethylene glycol. These tests were highly discriminant. Corynebacterium amycolatum displayed a unique profile, allowing it to be distinguished from similar species, such as C. xerosis, C. striatum, and C. minutissimum.
Journal of clinical microbiology, 1995
A total of 505 fermentative and 201 nonfermentative gram-negative bacilli, identified by conventi... more A total of 505 fermentative and 201 nonfermentative gram-negative bacilli, identified by conventional methods, were tested by the Crystal Enteric/Non-Fermenter ID kit and by the API 20E or API 20NE identification system. The overall correct results for fermenters were 92.9% by the Crystal kit and 89.1% by the API 20E system. The false identifications (genus and species incorrect) accounted for 3.1 and 7.1% for the Crystal and API systems, respectively. For nonfermenters, figures for correct identifications by the two systems were comparable (Crystal, 75.9%; API 20NE, 75.3%) while the API 20NE system gave twice as many incorrect results (13.8%) as Crystal (6.3%); however, Crystal failed to precisely identify several species included in a "miscellaneous" group. The Crystal Enteric/Non-Fermenter system is an easy-to-use kit which compares favorably with other commercial systems.
Mayo Clinic Proceedings, 2007
To investigate the risk factors for Staphylococcus aureus infective endocarditis (SAIE) and 6-mon... more To investigate the risk factors for Staphylococcus aureus infective endocarditis (SAIE) and 6-month mortality in patients with S aureus bacteremia (SAB). This study consisted of patients who were diagnosed as having nosocomial or community-acquired SAB or SAIE between June 1, 2000, and December 31, 2005. Clinical characteristics of patients with SAB were compared with those of patients with SAIE, and predictors of mortality in patients with SAB were analyzed. The median age of the 132 randomly selected patients with SAB and the 66 patients with SAIE was 66 and 68 years, respectively. Univariable analysis showed that unknown origin of SAB, a valvular prosthesis, a pacemaker, persistent fever, and persistent bacteremia were significantly associated with SAIE. In multivariable analysis, unknown origin of SAB (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.9-9.3; P=.001), a valvular prosthesis (OR, 9.2; 95% CI, 3.2-26.2; P<.001), persistent fever (OR, 3.1; 95% CI, 1.0-9.0; P=.04), and persistent bacteremia (OR, 6.8; 95% CI, 2.3-20.2- P=.001) were independently associated with SAIE. Six- month mortality was 8% in patients with SAB vs 35% in patients with SAIE (OR, 6.5; 95% CI, 2.9- 14.8; P<.001). In univariable analysis, methicillin- resistant S aureus (OR, 7.2; 95% CI, 1.7 - 29.4; P=.005) was significantly associated with 6-month mortality in patients with SAB. Unknown origin of SAB, a valvular prosthesis, persistent fever, and persistent bacteremia were independently associated with SAIE in patients with SAB. In univariable analysis, methicillin-resistant S aureus was associated with 6-month mortality in patients with SAB. S aureus infective endocarditis had a significantly higher mortality than SAB. The optimal management of SAB and SAIE deserves further study.
Clinical Microbiology Newsletter, 1997
Journal of Clinical Microbiology, 2014
Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-T... more Fluoroquinolones are the core drugs for the management of multidrug-resistant tuberculosis (MDR-TB). Molecular drug susceptibility testing methods provide considerable advantages for scaling up programmatic management and surveillance of drug-resistant TB. We describe here the misidentification of fluoroquinolone resistance by the GenoType MTBDRsl (MTBDRsl) (Hain Lifescience GmbH, Nehren, Germany) line probe assay (LPA) encountered during a feasibility and validation study for the introduction of this rapid drug susceptibility test in Kinshasa, Democratic Republic of Congo. The double gyrA mutation 80Ala and 90Gly represented 57% of all fluoroquinolone mutations identified from MDR-TB patient sputum samples, as confirmed by DNA sequencing. This double mutation was previously found to be associated with susceptibility to fluoroquinolones, yet it leads to absent hybridization of a wild-type band in the MTBDRsl and is thus falsely scored as resistance. Our findings suggest that MTBDRsl results must be interpreted with caution when the interpretation is based solely on the absence of a wild-type band without confirmation by visualization of a mutant band. Performance of the MTBDRsl LPA might be improved by replacing the gyrA wild-type probes by additional probes specific for well-documented gyrA mutations that confer clinically relevant resistance.