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I M Hoepelman

Publications and source records attributed to I M Hoepelman.

At least 37 records · Page 2Linked to original sources
PubMed2003

Reprogramming the host response in bacterial meningitis: how best to improve outcome?

Despite effective antibiotic therapy, bacterial meningitis is still associated with high morbidity and mortality in both children and adults. Animal studies have shown that the host inflammatory response induced by bacterial products in the subarachnoid space is associated with central nervous system injury. Thus, attenuation of inflammation early in the disease process might improve the outcome. The feasibility of such an approach is demonstrated by the reduction in neurologic sequelae achieved with adjuvant dexamethasone therapy. Increased understanding of the pathways of inflammation and neuronal damage has suggested rational new targets to modulate the host response in bacterial meningitis, but prediction of which agents would be optimal has been difficult. This review compares the future promise of benefit from the use of diverse adjuvant agents. It appears unlikely that inhibition of a single proinflammatory mediator will prove useful in clinical practice, but several avenues to reprogram a wider array of mediators simultaneously are encouraging. Particularly promising are efforts to adjust combinations of cytokines, to inhibit neuronal apoptosis and to enhance brain repair.

Animals↗
PubMed2003

Algorithm to determine cost savings of targeting antimicrobial therapy based on results of rapid diagnostic testing.

A rapid diagnosis of pneumococcal pneumonia may allow the earlier use of narrow-spectrum antimicrobial therapy. It is unknown, however, whether rapid diagnostic testing of patients hospitalized with community-acquired pneumonia (CAP) admitted to hospital lowers costs. Therefore, an algorithm to calculate the costs associated with the diagnosis and treatment of CAP was formulated. Subsequently, the algorithm was applied to clinical data for 122 consecutively admitted patients with CAP whose sputum samples were Gram stained and whose urine was tested for Streptococcus pneumoniae antigen. The costs of initial antimicrobial therapy, personnel, and materials were measured. Compared to the most expensive empirical regimen, rapid diagnostic testing would result in cost savings per patient (PP) of 3.51 Euros for Gram staining and 8.11 Euros for urinary pneumococcal antigen testing (1 Euro is equal to 1.13 US dollars, from 2000 to 2002). Compared to the cheapest regimen, Gram staining would increase the cost by 2.25 Euros PP, and urinary antigen testing would increase the cost by 24.26 Euros PP. In our setting, the use of rapid diagnostic testing would not lower costs. Cost savings depend, however, on the differences in the prices of the different antibiotics chosen and the proportion of evaluable and positive samples.

Adult↗
PubMed2002

Double-blind, placebo-controlled study comparing the effect of azithromycin with clarithromycin on oropharyngeal and bowel microflora in volunteers.

The purpose of this double-blind study was to assess the effect of azithromycin and clarithromycin on oral and fecal microflora. Bacterial species from fecal samples and throat washes from healthy volunteers were identified and quantified before, during and after receipt of either placebo ( n=6), azithromycin (500 mg once daily for 3 days; n=6) or clarithromycin (500 mg twice daily for 7 days; n=6). In both antibiotic groups, the changes in oropharyngeal aerobic microflora following antibiotic administration were minor. Antibiotics neither changed the bacterial load of Streptococcus spp. compared with placebo, nor did macrolide-resistant streptococci emerge. In the fecal aerobic microflora, the number of organisms of the family Enterobacteriaceae decreased slightly after antibiotic administration in both the clarithromycin and the azithromycin groups, but levels normalized by day 21 after therapy. No colonization with nonfermenters or Clostridium difficile was seen, and the total number of anaerobic bacteria was not affected in any study group. In conclusion, there were no significant differences between azithromycin and clarithromycin in their effect on human oropharyngeal and intestinal microflora, nor was the use of these antibiotics associated with colonization by resistant, gram-positive organisms or overgrowth of opportunistic microorganisms.

Adolescent↗
PubMed2002

[Asymptomatic bacteriuria; management choices in different patient groups].

Asymptomatic bacteriuria is a common medical condition, especially in women and elderly people. It is generally considered to be a benign condition, which does not require screening or antibiotic treatment. However, there are a few exceptions for which screening is possibly worthwhile. For children it is unclear whether the early detection of ASB can result in better clinical outcomes. Screening is therefore not advised, except for young children during the first few months after a symptomatic urinary tract infection. For pregnant women the use of screening for ASB is also unclear and in general not indicated. Research is necessary into the possible transition from ASB to pyelonephritis and the possible connection with low birth weight and premature births. There are indications that ASB in women with type I diabetes mellitus can lead to a deterioration in the renal function, yet these are insufficient to recommend screening as a routine procedure.

Anti-Infective Agents, Urinary↗
PubMed2001

[Urinary tract infections in women with diabetes mellitus].

Women with diabetes mellitus (DM) have asymptomatic bacteriuria (ASB) and urinary tract infections (UTIs) more frequently than women without DM. For type 1 diabetes mellitus, risk factors for asymptomatic bacteriuria include a longer duration of diabetes, peripheral neuropathy and macroalbuminuria. For type 2 diabetes, the risk factors are higher age, macroalbuminuria and a recent symptomatic UTI. Poorly-controlled diabetes and residual urine after urination are no risk factors. The most important risk factor for a UTI in type 1 diabetes patients is sexual intercourse. In type 2 diabetes patients the major risk factor is the presence of asymptomatic bacteriuria. This higher prevalence does not appear to be based on a difference in virulence of the causative microorganism. Differences in host response may explain this higher prevalence: E. coli with type 1 fimbriae adhere better to uroepithelial cells in women with DM than to those in women without DM; women with DM and ASB have lower urinary cytokine concentrations and leukocyte counts compared to women without DM and ASB; in vitro studies show that E. coli grow better when glucose is present in urine. There is no consensus on whether ASB should be treated in these patients. There are indications that UTIs in diabetes patients should be treated as complicated UTIs.

Bacteriuria↗
PubMed2001

[Candidate vaccine against urinary tract infections].

Urinary tract infections (UTIs) are an important medical problem for women. The most common uropathogen is Escherichia coli. The adherence of E. coli to the uroepithelium is mediated by the FimH adhesin, a minor component of type-1 fimbriae. This is the initial step in the pathogenesis of UTIs. Recently, a candidate vaccine has been developed, based on this FimH adhesin. In animal studies and in a phase 1 study, this vaccine has proven to be both immunogenic and safe. In this era of increasing resistance to antibiotics, such a method of prevention is of high importance.

Adhesins, Escherichia coli↗
PubMed2001

Long-term infectious complications and their relation to treatment duration in catheter-related Staphylococcus aureus bacteremia.

The optimal duration of treatment for catheter-related Staphylococcus aureus bacteremia is not known. Short courses (< or = 2 weeks) of therapy should be viewed with caution because essential data on late complications, such as osteomyelitis and metastatic abscesses, are lacking. This study represents a retrospective analysis of the data from 49 adult patients hospitalised in the period 1994-1996 (mean age, 57 years; range, 20-90 years; 47% male) and from whom Staphylococcus aureus was cultured concomitantly from peripheral blood and catheter segments. Forty-six venous catheters, two arterial catheters, and one unknown type of catheter were used. Forty-four patients were treated with effective anti-Staphylococcus aureus antibiotics. Twenty patients had a favourable outcome, defined as no complication and no death during 1 year of follow-up, 24 patients had complications, 14 patients died due to attributable mortality, and 5 other patients died of an underlying disease without showing signs or symptoms of a complication. Patients were categorised according to the duration of treatment. There were small differences between a shorter (1-14 days) and a longer (>14 days) course of antibiotics with regard to favourable outcome (41% vs. 33%), complications (48% vs. 53%), attributable death (31% vs. 20%), and death due to underlying disease (41% vs. 33%), respectively. The rates of complications and death were high, but a definite conclusion cannot be drawn because the study was underpowered. More randomised trials are needed, but, until the results of such trials are available, the duration of therapy should not be shortened to less than 14 days.

Adult↗
PubMed2001

Clinical diagnosis of influenza virus infection: evaluation of diagnostic tools in general practice.

BACKGROUND: With the development of new antiviral agents for influenza, the urge for rapid and reliable diagnosis of influenza becomes increasingly important. Respiratory virus infections are difficult to distinguish on clinical grounds. General practitioners (GPs) however, still depend on their clinical judgement. AIM: To evaluate the importance of clinical symptoms in the diagnosis of influenza virus infection. DESIGN OF STUDY: A multicentre questionnaire study. SETTING: Eighty-one patients from 14 general practices. METHOD: Patients with fever and at least one constitutional symptom and one respiratory symptom were included. A questionnaire with the medical history and clinical symptoms was completed and a combined nose-throat swab was taken. Virus culture, rapid culture, and polymerase chain reaction (PCR) amplification were performed on each specimen. Multivariate analysis was used to obtain the best predictive model. RESULTS: By using PCR, an increase was seen in the detection of the viral pathogens compared with the results of culture. In 42 out of 81 patients PCR was positive for influenza. A positive predictive value (PPV) of 75% was observed for the combination of headache at onset, feverishness at onset, cough, and vaccination status during the period of increase influenza activity. Criteria used by the ICHPPC-2 resulted in a PPV of 54%. The PPV for diagnosis made by the GP was 76%. CONCLUSION: Although influenza is difficult to diagnose on clinical grounds, the GPs in this study were able to diagnose influenza as such more accurately on their judgement than by the other criteria.

Adult↗
PubMed2000

Quantitative analysis of phagocytosis of Cryptococcus neoformans by adherent phagocytic cells by fluorescence multi-well plate reader.

Macrophages and monocytes are adherent phagocytic cells which play an important role in host defence against the yeast-like fungus Cryptococcus neoformans. Before, phagocytosis by adherent phagocytes could only be measured by means of microscopy or by a radioactive assay, which both have obvious disadvantages. We have developed a new, rapid and objective method to measure phagocytosis of C. neoformans by adherent phagocytes (e.g. alveolar macrophages) using a fluorescence multi-well plate reader. This method allows us to discriminate accurately between adherence and internalisation of C. neoformans by macrophages during long term incubation. In addition, the method was used to study the role of the mannose receptor in phagocytosis of the acapsular yeast in the absence of serum by human monocyte-derived macrophages (MDM).

Cell Adhesion↗
PubMed2000

Selective digestive decontamination in patients in intensive care. The Dutch Working Group on Antibiotic Policy.

Selective digestive decontamination (SDD) is the most extensively studied method for the prevention of infection in patients in intensive care units (ICUs). Despite 27 prospective randomized studies and six meta-analyses, routine use of SDD is still controversial. In this review, we summarize the available scientific information on effectiveness of SDD in ICU patients. The effects of SDD have been studied in different combinations of the concept, using different antibiotics. Comparison of the individual studies, therefore, is difficult. In most studies, SDD resulted in significant reductions in the number of diagnoses of ventilator-associated pneumonia. However, incidences of ventilator-associated pneumonia in control groups ranged from 5% to 85%. Moreover, these reductions in incidences of ventilator-associated pneumonia in individual studies were not associated with improved patient survival, reductions of duration of ventilation or ICU stay, or reductions in antibiotic use. The numbers of patients studied are too small to determine effects on patient survival. Although two meta-analyses suggested a 20% mortality reduction when using the full concept of SDD (topical and systemic prophylaxis) these results should be interpreted with caution. Formal cost-benefit analyses of SDD have not been performed. SDD is associated with the selection of microorganisms that are intrinsically resistant to the antibiotics used. However, the studies are too small and too short to investigate whether SDD will lead to development of antibiotic resistance. As long as the benefits of SDD (better patient survival, reduction in antibiotic use or improved cost-effectiveness) have not been firmly established, the routine use of SDD for mechanically ventilated patients is not advised.

Antibiotic Prophylaxis↗
PubMed1999

[Legionella epidemic in the Netherlands].

In March 1999 an epidemic of Legionella pneumonia developed in the province of Noord Holland, the Netherlands: by the end of April 233 patients had become ill after a visit to a flower show, in 106 of whom the diagnosis of Legionella pneumonia was established, while in 48 the disease was probable and in 4 it was possible; 23 patients died, in 16 of whom the diagnosis of legionnaires' disease was established. In 37 patients Legionella pneumophila was isolated. There was a significant association with stands on the show that displayed anticondense fluids to clean glasses, steam ironing machines and whirlpools and bubble baths, making a relation to aerosol transmission of the causative agent very probable. Legionella (the same serotype) was indeed isolated from a whirlpool. As Legionella can readily be isolated from the human environment, a limited number of species can cause disease and laboratory tests are expensive and time consuming, an effective primary preventive programme is an illusion. Prevention should be aimed at monitoring the environment of susceptible hosts and tracing sources of infection of index cases. Patients with severe pneumonia requiring intensive care must be treated with antibiotics that cover Legionella, until this cause is excluded.

Anti-Bacterial Agents↗
PubMed1999

[Ventilator-associated pneumonia; controversies with respect to diagnosis, pathogenesis, therapy and prevention].

Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection among intensive care patients; it is associated with increased morbidity and mortality. VAP is always preceded by colonization of the upper respiratory tract with potentially pathogenic micro-organisms. Oropharyngeal colonization is pivotal in the pathogenesis of VAP, while gastric and intestinal colonization appear to be less important than generally believed. The diagnosis is difficult and usually relies on a combination of clinical, microbiological and radiographic criteria. This combination of criteria may have a high sensitivity for VAP, but specificity is low. As a result, many patients receive antibiotics unnecessarily. Bronchoscopic sampling of lower airways can increase specificity, but whether these relatively expensive techniques are cost-effective remains to be established. The best antibiotic therapy for VAP is unknown. General infection control measures remain the cornerstone of infection prevention in each intensive care unit (ICU). Selective digestive decontamination (SDD) was associated with a reduction in the incidence of VAP, but mortality rates remained largely unaffected, and selection of antibiotic-resistant pathogens remains a potential disadvantage. Routine SDD in ICU is discouraged. Decontamination of the oropharynx appears to be equally effective.

Antibiotic Prophylaxis↗
PubMed1999

Guidelines for severe community-acquired pneumonia in the western world.

BACKGROUND: Recently, several guidelines (ATS 1993/IDSA 1998; ERS 1998; SWAB 1998) have been issued for the initial therapy of patients with community-acquired pneumonia. In patients who fulfil the criteria for severe community-acquired pneumonia (SCAP), it was advised to start with a macrolide (active against Legionella spp. and Mycoplasma pneumoniae) in combination with an agent active against both pneumococci and Pseudomonas aeruginosa by the ATS/IDSA guidelines, while the ERS suggested starting with a second or third generation cephalosporin, in combination with either a macrolide or second generation quinolon plus or minus rifampicin. In the SWAB guidelines, no recommendations for SCAP were made. METHODS: Sixty-two cases admitted to the intensive care units of a tertiary-care university hospital with SCAP between 1992 and 1996 were studied retrospectively. The causative pathogens, clinical and laboratory characteristics of severity, antibiotic therapy and mortality were analysed. Immunocompromised patients, patients using immunosuppressive agents and patients with a malignancy were excluded. RESULTS: Indices of severe illness were widely seen and 37% developed shock while 45% required vasoactive drugs. Bilobular or multilobular abnormalities were seen in 34% of the patients. Forty-five patients (73%) required artificial respiration and 54 (87%) had an underlying disease. The overall mortality was 42%. In 41 patients (66%), a pathogen was isolated. The most frequent causes of SCAP in this study were Streptococcus pneumoniae (22 cases or 35%), Haemophilus influenzae (seven cases or 11%), Pseudomonas aeruginosa (four cases or 7%), and other Enterobacteriaceae (twice in combination with pneumococci and once with H. influenzae). Legionella pneumophila was identified in three cases. In patients with severe chronic obstructive pulmonary disease (COPD), pneumococci were the most important pathogens six cases or 27%), followed by P. aeruginosa (14%) and H. influenzae (14%). CONCLUSIONS: The guidelines for the management of SCAP issued by the ATS and IDSA in 1993 are only partially adequate in the Dutch setting. Coverage of P. aeruginosa would seem useful, given the fact that isolation of this pathogen has been shown to be a predictor of mortality, but only in patients with severe COPD or structural disease of the lung, and especially in patients in whom the Gram stain reveals Gram-negative rods, as is also suggested in the revised IDSA guidelines (1998). Risk factors for P. aeruginosa could be added to the ERS guidelines. Including SCAP as a separate entity in the SWAB guidelines may be useful.

Adult↗
PubMed1999

Pulmonary surfactant protein A binds to Cryptococcus neoformans without promoting phagocytosis.

BACKGROUND: Evidence is accumulating that the alveolar collecting surfactant protein A (SP-A) plays an important role in the first line of defence against infiltrating pathogenic micro-organisms and viruses. The ability of SP-A to facilitate the binding and uptake of acapsular Cryptococcus neoformans by monocyte-derived macrophages, human alveolar macrophages, monocytes and polymorphonuclear leucocytes was investigated. MATERIALS AND METHODS: Binding, competition and phagocytosis experiments were performed using a flow cytometry technique. RESULTS: SP-A bound to both the acapsular and the encapsulated form of C. neoformans in a concentration-dependent manner. SP-A showed a threefold better binding to the acapsular yeast: this binding was partly calcium dependent and could be inhibited by mannose (ID50 = 3 mmol L-1) and glucose (ID50 = 2.1 mmol L-1) but not by galactose (ID50 = 391 mmol L-1). SP-A did not function as an opsonin in phagocytosis of acapsular C. neoformans for any of the phagocytes studied. CONCLUSION: Our results indicate that SP-A binds in a concentration-dependent manner to both encapsulated and acapsular C. neoformans. Despite SP-A binding to the acapsular C. neoformans, phagocytosis by various phagocytes was not enhanced.

Animals↗
PubMed1999

Cryptococcus neoformans and its cell wall components induce similar cytokine profiles in human peripheral blood mononuclear cells despite differences in structure.

We studied the cytokine profile of peripheral blood mononuclear cells after stimulation with various cryptococcal strains or its purified cell wall components. After 3 h of stimulation, tumor necrosis factor (TNF) alpha levels were strongly increased, whereas interferon (IFN) gamma and interleukin (IL) 10 levels were increased only slightly, or not at all (respectively). In contrast, after 18 h, TNF-alpha and IFN-gamma levels were (strongly) decreased, whereas the IL-10 levels were increased. The IL-1beta, IL-6 and IL-8 levels were equally high throughout the experiment. In order to establish which of the cryptococcal envelope components contributed most to the observed cytokine profile induced by whole cryptococci, glucuronoxylomannan, galactoxylomannan and mannoproteins were purified and partially characterized biochemically. All cryptococcal components elicited a similar cytokine pattern despite the differences in structure.

Blood Donors↗
PubMed1998

[A changed pattern of opportunistic infections and malignancies in HIV-seropositive patients after the introduction of intensive anti-HIV-combination therapy].

The application of potent combinations of antiretroviral drugs ('highly active antiretroviral therapy' (HAART)) makes effective therapy of HIV infection feasible. Consequently, the pattern of opportunistic infections and other secondary complications has changed. The incidence of infections and mortality due to aids has declined significantly. Further, the occurrence of other infections and syndromes, till now unknown in patients with aids, has been observed. It is thought that these are caused by HAART-induced inflammation, a phenomenon due to immune enhancement following HAART. An important issue is whether primary and secondary prophylaxis against opportunistic infections can be discontinued after improvement of the immune system: indeed, there are reports that discontinuation is safe in patients with persistent CD4+ cell counts above the critical level for that particular infection while CD4+ cell counts are monitored carefully.

AIDS-Related Opportunistic Infections↗