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Dive into the research topics where A. Fleer is active.

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Featured researches published by A. Fleer.


Clinical Infectious Diseases | 2001

Neonatal Sepsis by Campylobacter jejuni: Genetically Proven Transmission from a Household Puppy

Tom F. W. Wolfs; Birgitta Duim; Sibyl P. M. Geelen; Alan Rigter; Fiona Thomson-Carter; A. Fleer; Jaap A. Wagenaar

We report a case of neonatal Campylobacter jejuni sepsis in a 3-week-old infant who acquired the infection through transmission from a recently acquired household puppy. Genotyping of Campylobacter strains obtained from puppy and child resulted in highly homogeneous findings. This represents the first genetically proven C. jejuni dog-human transmission.


Journal of Antimicrobial Chemotherapy | 2010

Variation in antibiotic use in neonatal intensive care units in the Netherlands

T. B. Y. Liem; Tannette G. Krediet; A. Fleer; T. C. G. Egberts; C. M. A. Rademaker

OBJECTIVESnTo examine the variation in quantity and classes of antibiotics used in all 10 tertiary care neonatal intensive care units (NICUs) in the Netherlands during 2005.nnnMETHODSnWe collected data from all tertiary care NICUs in the Netherlands on clinical and demographic characteristics and the type and quantity of systemic antibiotic use [expressed as defined daily doses (DDD)/100 admissions] in 2005. Antibiotics were ranked by volume of DDDs, and those antibiotics which accounted for 90% of the total volume of use [drug utilization (DU) 90%] were noted.nnnRESULTSnAntibiotic consumption ranged from 130 to 360 DDD/100 admissions. In total, 9-24 different antibiotics were used, of which 3-10 were in the DU90% segment.nnnCONCLUSIONSnBy comparing antibiotic use in Dutch NICUs we found a considerable variation in the number of different antibiotics used and in the total amount of antibiotic use. Further exploration of the opportunities to reach consensus in antibiotic policy, and to increase attention to antibiotic stewardship, is recommended.


Journal of Hospital Infection | 1988

Host defence to bacterial infection in the neonate

A. Fleer; L.J. Gerards; J. Verhoef

Host defence to bacterial infection is mainly determined by opsonins, i.e., IgG antibodies and complement, and phagocytic cells, which co-operate to remove bacterial invaders from host tissues. Various studies have clearly documented distinct defects in both arms of host defence in the newborn period. Chemotaxis, i.e., directed migration of polymorphonuclear leukocytes (PMN) is impaired in the neonate. Phagocytosis of bacteria by neonatal PMN is normal, but post-phagocytic events, particularly metabolic activation and bacterial killing are impaired, the latter defect apparently due to diminished generation of reactive oxygen species. Both classical and alternative pathway activity of complement are mildly diminished (50-80% of adult values) in the term newborn, but are more severely decreased in the premature infant (20-40% of adult values in 28 to 36 weeks prematures). Opsonic activity of transplacentally-derived IgG when compared to maternal IgG is strikingly deficient against staphylococci and group B streptococci (GBS), in the latter case depending on the GBS serotype. Since opsonization is a key process in antibacterial defence, it is speculated that these opsonic defects of IgG may be an essential determinant of the neonates susceptibility to disease due to these bacteria.


Journal of Perinatal Medicine | 1990

Pneumococcal septicemia in the newborn. A report on seven cases and a review of the literature

Sibyl P. M. Geelen; Leo J. Gerards; A. Fleer

This report summarizes the essential findings of seven cases of pneumococcal septicemia in the newborn and compares the data with those reported in the literature. It is emphasized that pneumococcal septicemia is a rare but highly lethal disease of the newborn. The clinical course strongly resembles early onset group B streptococcal disease. Epidemiological data suggest that the majority of infants are colonized near birth. Analogous to group B streptococcal sepsis, it seems rational to administer penicillin prophylaxis during labor to women with S. pneumoniae isolated from their genital tract to prevent vertical transmission and neonatal pneumococcal septicemia.


Neonatology | 2011

A Seven-Year Survey of Management of Coagulase-Negative Staphylococcal Sepsis in the Neonatal Intensive Care Unit : Vancomycin May Not Be Necessary as Empiric Therapy

Marieke A. C. Hemels; Agnes van den Hoogen; Malgorzata A. Verboon-Maciolek; A. Fleer; Tannette G. Krediet

Background: The typical empiric therapy for coagulase-negative staphylococcal (CONS) sepsis includes vancomycin. In our neonatal intensive care unit, we have consistently avoided the use of vancomycin to treat CONS sepsis, except for specific cases, and have used instead cefazolin as empiric agent. Objectives: The clinical outcome of infants with CONS sepsis was evaluated in relation to the susceptibility of CONS blood isolates to cefazolin over a period of 7 years. Methods: Clinical characteristics, symptoms of sepsis and antibiotic use were studied retrospectively. Susceptibility of CONS blood isolates to cefazolin was determined by E-test. Results: Of 163 infants with proven CONS sepsis, 121/140 (86%) infants with a cefazolin-susceptible (minimum inhibition concentration (MIC) ≤8 mg/l) and 21/23 (91%) with a cefazolin-resistant (MIC ≧32 mg/l) blood isolate were treated with cefazolin. 21 (13%) infants were switched to vancomycin, in only 3 of them CONS had become resistant to cefazolin. The majority (81%) of the infants with a good response to cefazolin had the indwelling central venous catheter removed, in contrast to only 22% of the infants with cefazolin treatment failure. Median cefazolin MIC values were 0.75–2 mg/l during the study period. Conclusions: The great majority of infants with CONS sepsis was successfully treated with cefazolin. The use of vancomycin could be restricted to specific cases. Despite the consistent use of cefazolin in neonatal CONS sepsis over an extended period of time, cefazolin MIC values remained low and in the susceptible range. Removal of the central venous catheter in infants with clinical symptoms of sepsis is an important therapeutic measure.


Therapeutic Drug Monitoring | 2001

Once-daily versus multiple-daily gentamicin in infants and children.

Esther V. Uijtendaal; Catherine M. A. Rademaker; Alfred F. A. M. Schobben; A. Fleer; William L. M. Kramer; Adrianus J. van Vught; Jan L. L. Kimpen; Aalt Van Dijk

In this prospective randomized trial, the efficacy and safety of once-daily administration of gentamicin were compared with multiple-daily administration in infants and children. In addition, pharmacokinetic variables were calculated. Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose or dosage interval adjustments to achieve target levels. Fifty-two infants and children aged 1 month (postterm) to 16 years were enrolled. The duration of fever from the start of therapy, the percentage decline of C-reactive protein (CRP) on day 3 of treatment, and the clinical outcome were used as efficacy parameters. Nephrotoxicity was evaluated using creatinine serum levels. Basic characteristics in both groups were comparable. A good clinical response was observed in both groups. Fever may have resolved faster with multiple-daily administration, but this was not statistically significant. The percentage of decline of CRP was also comparable in both groups. Nephrotoxicity occurred in six patients, three per group. Many patients were too ill or too young to perform hearing tests, but no clinical signs of ototoxicity were observed. Mean doses of 6.8 mg/kg per day (multiple-daily administration) and 7.3 mg/kg per day (once-daily administration) were necessary to meet the target gentamicin levels. Triple-daily doses had to be reduced to a twice-daily regimen in 17 of 26 children. Dose and dosage interval adaptations can be performed by Bayesian forecasting using a one-compartment model with one set of K e and V d parameters. The authors consider both regimens equally effective, with a comparable incidence of nephrotoxicity. A starting dose of 6.5 mg/kg once daily is advised.


European Journal of Pediatrics | 2000

Severe neonatal group A streptococcal disease

Malgorzata A. Verboon-Maciolek; Tannette G. Krediet; Ingrid van Ertbruggen; Leo J. Gerards; A. Fleer

Abstract Since the mid-1980s, an increase in incidence of invasive disease caused by group A streptoccoci has been noted amongst adults and children; however, neonatal disease is still rare. Between 1979 and 1998, seven neonates with severe group A streptoccocal disease were admitted to our neonatal intensive care unit. The clinical presentation, treatment and outcome are described. In three cases of early-onset disease vertical transmission was documented.nConclusion Because the incidence of group A streptococcal disease in the general population seems to have increased over the last two decades, we should be aware of the possibility and particularly the severity of group A streptococcal disease in the neonatal period.


European Journal of Clinical Investigation | 2003

Pneumococcal immune adherence to human erythrocytes

Jeanne-Marie Hament; H van Dijk; A. Fleer; Piet C. Aerts; M Schoenmakers; Mw de Snoo; Bhat Dekker; Jll Kimpen; Tfw Wolfs

Background Human red blood cells bind various C3b‐coated microorganisms via their C3b/CR1 receptor, a phenomenon referred to as immune adherence. The aim of the present study was to measure pneumococcal adherence to human red blood cells by flow cytometry and to study kinetic aspects of this binding.


Clinical Microbiology and Infection | 2008

Pseudomonas aeruginosa diversity in distinct paediatric patient groups

Gerdien A. Tramper-Stranders; C.K. van der Ent; T.F.W. Wolfs; Jan L. L. Kimpen; A. Fleer; U Johansen; Helle Krogh Johansen; Niels Høiby

Pseudomonas aeruginosa is a pathogen that often infects patients who are either immunocompromised or have local defects in host defences. It is known that cystic fibrosis (CF) patients are sometimes infected with certain clonal isolates. It is not clear whether these clonal isolates also infect non-CF patients and whether clonality of isolates occurs in other patient groups. The aim of this study was to investigate P. aeruginosa diversity and the occurrence of clones within five distinct paediatric patient groups susceptible to P. aeruginosa infection. P. aeruginosa isolates were cultured from 157 patients (CF first infection (CF-1 group) (29); CF chronic infection (CF-chronic group) (27); urinary tract infection (34); chronic suppurative otitis media (43); and intensive-care hospitalization/immunodeficiency (24)). All 202 phenotypically different isolates were tested for antimicrobial resistance and further typed by pulsed-field gel electrophoresis. Simpsons diversity index was calculated for the five groups. CF-chronic patients carried the highest number of distinct P. aeruginosa phenotypes and genotypes per culture. Isolates from the CF-chronic group were significantly less diverse than those from the other groups. A group of clonal isolates was observed among patients from the CF-chronic and CF-1 groups. These or different clonal isolates were not encountered among the three other patient groups. No characteristic resistance pattern could be identified among isolates from the distinct patient groups and among the clonal isolates. In conclusion, isolates of the CF-chronic group were less diverse than those in the other patient groups with P. aeruginosa infection; clonal isolates were not encountered in non-CF patients. Transmission of clonal CF isolates to other patient groups was not observed.


European Journal of Pediatrics | 1999

Lethal encephalopathy complicating childhood shigellosis

Frans B. Plötz; H. G. M. Arets; A. Fleer; R. J. B. J. Gemke

Abstract A 6-year-old girl is described who died following rapid neurological deterioration, ending in lethal cerebral oedema. Despite the absence of severe intestinal and metabolic derangement, Shigella was cultured from the stool. Toxic encephalopathy is responsible for death following this rare complication of childhood shigellosis in developed countries. The pathophysiology is unknown.nConclusion Lethal toxic encephalopathy can be caused by Shigella despite the absence of severe intestinal and metabolic derangement. If shigelllosis is suspected, headache may be a first significant sign for the development of toxic encephalopathy. Early recognition and rapid measures to prevent brain oedema may improve outcome.

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Jan L. L. Kimpen

Boston Children's Hospital

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C.K. van der Ent

Boston Children's Hospital

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J. Verhoef

University of Minnesota

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