Jan Verhoef

Bio: Jan Verhoef is an academic researcher from Utrecht University. The author has contributed to research in topics: Antibody & Phagocytosis. The author has an hindex of 63, co-authored 331 publications receiving 15399 citations. Previous affiliations of Jan Verhoef include VU University Amsterdam & Manchester Royal Infirmary.

Multilocus Sequence Typing of Klebsiella pneumoniae Nosocomial Isolates

Abstract: A multilocus sequence typing (MLST) scheme was developed for Klebsiella pneumoniae. Sequences of seven housekeeping genes were obtained for 67 K. pneumoniae strains, including 19 ceftazidime- and ciprofloxacin-resistant isolates. Forty distinct allelic profiles were identified. MLST data were validated against ribotyping and showed high (96%) discriminatory power. The MLST approach provides unambiguous data useful for the epidemiology of K. pneumoniae isolates.

Emerging Importance of Multidrug-Resistant Acinetobacter Species and Stenotrophomonas maltophilia as Pathogens in Seriously Ill Patients: Geographic Patterns, Epidemiological Features, and Trends in the SENTRY Antimicrobial Surveillance Program (1997–1999)

Abstract: As part of the SENTRY Antimicrobial Surveillance Program, a total of 1078 Acinetobacter species and 842 Stenotrophomonas maltophilia isolates were collected between January 1997 and December 1999 from 5 geographic regions (Canada, the United States, Latin America, Europe, and the Asia-Pacific). The frequency of infections (by geographic region and body site), including those due to imipenem-resistant Acinetobacter species and trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant S. maltophilia, was evaluated. The possibility of seasonal variations in bloodstream infections caused by Acinetobacter species was studied, as was the activity of several therapeutic antimicrobials against all strains. Acinetobacter species and S. maltophilia were most frequently associated with pulmonary infections, independent of the region evaluated. In contrast, patterns of antimicrobial resistance markedly varied among distinct geographic regions, especially for nosocomial isolates. Although the carbapenems were the most active antimicrobials against Acinetobacter species, nearly 11.0% of the nosocomial isolates were resistant to this drug group in both regions. TMP-SMZ, ticarcillin-clavulanic acid, gatifloxacin, and trovafloxacin were the only agents with consistent therapeutic activity against S. maltophilia isolates. Rates of resistance to TMP-SMZ ranged from 2% in Canada and Latin America to 10% in Europe. The geographic differences in resistance patterns among Acinetobacter species and S. maltophilia isolates observed in this study emphasize the importance of local surveillance in determining the most adequate therapy for acinetobacter and S. maltophilia infections and the possible clonal, epidemic nature of occurrence.

Pulmonary surfactant protein A enhances the host-defense mechanism of rat alveolar macrophages.

Abstract: The effects of surfactant, surfactant lipids, and surfactant protein A (SP-A) on the surface phagocytosis of [3H]thymidine-labeled Staphylococcus aureus (SAE) by rat alveolar macrophages were studied. Alveolar macrophages only ingest SAE when the bacteria are opsonized with rat serum prior to incubation with alveolar macrophages. Preincubation or “opsonization” of the bacteria with surfactant did not result in phagocytosis by the macrophages. However, preincubation of the macrophages with surfactant increased the phagocytosis of rat serum-opsonized bacteria by approximately 70% when compared to the control macrophages. The factor present in surfactant causing the stimulation of the phagocytosis is probably SP-A. Preincubation of macrophages with human SP-A enhanced the phagocytosis to the same extent as whole surfactant, whereas preincubation with surfactant lipids had no effect on the phagocytosis. The SP-A-induced enhancement of the phagocytosis is time, temperature, and concentration dependent. Phagocy...

Lipoprotein metabolism in patients with severe sepsis

Abstract: Objective: Lipoproteins have been implicated to play a role in innate immunity. Changes in lipoprotein levels have been reported in a variety of inflammatory disorders. Not much is known about lipoprotein metabolism in patients with severe sepsis. We conducted an ancillary study in a multiple-center phase III sepsis trial to investigate the dynamics of plasma lipoproteins in patients with severe sepsis. Design: Prospective analysis in patients meeting criteria for severe sepsis as part of a multiple-center sepsis study (KyberSept) with antithrombin III (Kybernin P). Setting: University hospital intensive care unit. Patients: Seventeen patients were included in the study. Interventions: Randomized patients received a loading dose of 6000 IU of antithrombin III (Kybernin P) or placebo followed by a 96-hr continuous infusion of 250 IU/hr antithrombin III (Kybernin P) or placebo. In each patient, serial blood samples for total cholesterol, lipoprotein cholesterol, triglycerides, apolipoprotein A-1, apolipoprotein B, and C-reactive protein determination as well as clinical data were collected over 28 days. Measurements and Main Results: Plasma cholesterol levels rapidly decreased from 2.67 2.02 mmol/L on day 0 to a nadir of 1.41 0.70 mmol/L on day 3, followed by a slow increase to 4.18 1.94 mmol/L on day 28. High-density lipoprotein (HDL) cholesterol concentrations decreased rapidly from 0.84 0.92 mmol/L to a nadir of 0.42 0.35 mmol/L on day 3, to show a slow increase during the following 4 wks to 0.84 0.42 mmol/L. The low-density lipoprotein (LDL) cholesterol concentrations were already low (0.94 0.81 mmol/L) at study entry, to show a progressive increase to subnormal values (2.01 0.94 mmol/L) at 4 wks. Nadir and recovery lipoprotein concentrations were significantly different (paired Student’s t-test, p < .05). A significant correlation was found between HDL cholesterol and apolipoprotein A-1 (r .714, p < .05) and between LDL cholesterol and apolipoprotein B (r .733, p < .05). There was no statistical difference in lipoprotein concentrations either between survivors and nonsurvivors or between patients receiving antithrombin III or placebo. Serum amyloid A was a major apoprotein (45%) in HDL at the start of the sepsis and was slowly replaced by apolipoprotein A-1 during recovery. A positive correlation was found between plasma C-reactive protein concentrations and serum amyloid A concentrations in HDL (r .684, p < .05). No other relevant correlations were found between inflammatory and lipoprotein parameters. Conclusions: In patients with severe sepsis, lipoprotein concentrations rapidly change and can be reduced to 50% of recovery concentrations. The pattern of early rapid decline is found primarily in the HDL and a slow recovery in both HDL and LDL fractions. The correlation between apolipoprotein and lipoprotein cholesterol concentrations suggests a decline in lipoprotein particles. During severe sepsis, HDL is shifted to acute phase HDL, which is enriched in serum amyloid A and depleted of cholesterol and apolipoprotein A-1. Lipoprotein concentrations are unable to discriminate between survivors and nonsurvivors. (Crit Care Med 2003; 31:1359 ‐1366)

Staphylococcus aureus infections.

Abstract: Micrococcus, which, when limited in its extent and activity, causes acute suppurative inflammation (phlegmon), produces, when more extensive and intense in its action on the human system, the most virulent forms of septicaemia and pyaemia.1 In an elegant series of clinical observations and laboratory studies published in 1880 and 1882, Ogston described staphylococcal disease and its role in sepsis and abscess formation.1,2 More than 100 years later, Staphylococcus aureus remains a versatile and dangerous pathogen in humans. The frequencies of both community-acquired and hospital-acquired staphylococcal infections have increased steadily, with little change in overall mortality. Treatment of these infections . . .

Neuroinflammation in Alzheimer's disease

Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

Antimicrobial-Resistant Pathogens Associated with Healthcare- Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010

Abstract: Objective. To describe antimicrobial resistance patterns for healthcare-associated infections (HAIs) reported to the National Healthcare Safety Network (NHSN) during 2009-2010. Methods. Central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections were included. Pooled mean proportions of isolates interpreted as resistant (or, in some cases, nonsusceptible) to selected antimicrobial agents were calculated by type of HAI and compared to historical data. Results. Overall, 2,039 hospitals reported 1 or more HAIs; 1,749 (86%) were general acute care hospitals, and 1,143 (56%) had fewer than 200 beds. There were 69,475 HAIs and 81,139 pathogens reported. Eight pathogen groups accounted for about 80% of reported pathogens: Staphylococcus aureus (16%), Enterococcus spp. (14%), Escherichia coli (12%), coagulase-negative staphylococci (11%), Candida spp. (9%), Klebsiella pneumoniae (and Klebsiella oxytoca; 8%), Pseudomonas aeruginosa (8%), and Enterobacter spp. (5%). The percentage of resistance was similar to that reported in the previous 2-year period, with a slight decrease in the percentage of S. aureus resistant to oxacillins (MRSA). Nearly 20% of pathogens reported from all HAIs were the following multidrug-resistant phenotypes: MRSA (8.5%); vancomycin-resistant Enterococcus (3%); extended-spectrum cephalosporin-resistant K. pneumoniae and K. oxytoca (2%), E. coli (2%), and Enterobacter spp. (2%); and carbapenem-resistant P. aeruginosa (2%), K. pneumoniae/oxytoca (<1%), E, coli (<1%), and Enterobacter spp. (<1%). Among facilities reporting HAIs with 1 of the above gram-negative bacteria, 20%-40% reported at least 1 with the resistant phenotype. Conclusion. While the proportion of resistant isolates did not substantially change from that in the previous 2 years, multidrug-resistant gram-negative phenotypes were reported from a moderate proportion of facilities.

Extended-spectrum beta-lactamases: a clinical update.

Abstract: Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.