[The current MRSA policy in the Netherlands].
Explore the source record for details and available documents.
Health Policy↗
Biomedical subjects
H A Verbrugh
Publications and source records attributed to H A Verbrugh.
An additional measure for quantifying antibiotic use in hospitals.
OBJECTIVES: The number of defined daily doses (DDD) per 100 patient days is often used as an indicator for the selection pressure exerted by antibiotics in the hospital setting. However, this unit of measurement does not fully describe the selection pressure and is sensitive to changes in hospital resource indicators. Additional information is required to facilitate interpretation of this indicator. The number of DDD per 100 admissions could be a valuable additional tool. The aim of this study is to investigate the importance of units of measurement in quantifying antibiotic use data with regards to antibiotic resistance risks. PATIENTS AND METHODS: Trends in antibiotic use in acute care Dutch hospitals between 1997-2001 were studied. Antibiotic use was expressed in DDD per 100 patient days and in DDD per 100 admissions. RESULTS: From 1997 to 2001, total systemic antibiotic use significantly increased from 47.2 to 54.7 DDD per 100 patient days, whereas expressed in DDD per 100 admissions it remained constant. Some individual antibiotics increases in DDD per 100 patient days were not accompanied by increases in DDD per 100 admissions and vice versa. The mean number of total DDD per hospital decreased (not significantly) between 1997 and 2001. The mean number of patient days, admissions and length of stay decreased significantly. CONCLUSIONS: Knowledge of variation in resource indicators and additional expression of the data in DDD per 100 admissions is imperative for a meaningful understanding of observed trends in antibiotic use expressed in DDD per 100 patient days. Further research is needed to determine the correlation between different measures of antibiotic use and the level of antibiotic resistance.
Anti-Bacterial Agents↗
Epidemiology of nasopharyngeal carriage of Neisseria meningitidis in healthy Dutch children.
We investigated the prevalence and determinants of nasopharyngeal carriage of Neisseria meningitidis in 3200 healthy children aged 1-19 years. The incidence of meningococcal carriage was, on average, 1.5%. Peak incidences were seen at age 1 year and after age 15 years. The independent determinants of meningococcal carriage included age, regular visits to youth clubs (odds ratio [OR], 2.2) and discotheques (OR, 4.3), and pneumococcal carriage (OR, 4.1).
Adolescent↗
Use of pooled urine samples and automated DNA isolation to achieve improved sensitivity and cost-effectiveness of large-scale testing for Chlamydia trachomatis in pregnant women.
The success of large-scale screening for Chlamydia trachomatis depends on the availability of noninvasive samples, low costs, and high-quality testing. To evaluate C. trachomatis testing with pregnant women, first-void urine specimens from 750 consecutive asymptomatic pregnant women from the Rotterdam area (The Netherlands) were collected. Initially, we investigated the performance of three different DNA isolation methods with 350 of these urines and 70 pools of 5 of the same subset of urine samples. The routinely used COBAS AMPLICOR test was compared to the COBAS AMPLICOR test with prior DNA isolation by use of the MagNA Pure large-volume kit and the MagNA Pure bacterial DNA isolation kit. The latter combination provided the best DNA test for pooled urines, with a sensitivity twice that of the other methods. Next, using all 750 urines, the COBAS AMPLICOR performance for individual testing was compared to pooled testing with the standard COBAS AMPLICOR procedure and subsequently to pooled testing with COBAS AMPLICOR in combination with the MagNA Pure bacterial DNA isolation kit. The sensitivity of COBAS AMPLICOR was 65% on individual and 42% on pooled urines but improved to 92% on pooled urines with the MagNA Pure bacterial DNA isolation kit, making this combination the best screening method. The C. trachomatis prevalence in this population appeared to be 6.4%. Additionally, the cost of the combined MagNA Pure bacterial DNA isolation kit and COBAS AMPLICOR method on pooled urines was only 56% of the cost of the standard COBAS AMPLICOR test applied to individual urines. Costs per positive case detected in the combined method were 39% of standard costs.
Automation↗
Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children.
A trial with a 7-valent pneumococcal-conjugate vaccine in children with recurrent acute otitis media showed a shift in pneumococcal colonisation towards non-vaccine serotypes and an increase in Staphylococcus aureus-related acute otitis media after vaccination. We investigated prevalence and determinants of nasopharyngeal carriage of Streptococcus pneumoniae and S aureus in 3198 healthy children aged 1-19 years. Nasopharyngeal carriage of S pneumoniae was detected in 598 (19%) children, and was affected by age (peak incidence at 3 years) and day-care attendance (odds ratio [OR] 2.14, 95% CI 1.44-3.18). S aureus carriage was affected by age (peak incidence at 10 years) and male sex (OR 1.46, 1.25-1.70). Serotyping showed 42% vaccine type pneumococci. We noted a negative correlation for co-colonisation of S aureus and vaccine-type pneumococci (OR 0.68, 0.48-0.94), but not for S aureus and non-vaccine serotypes. These findings suggest a natural competition between colonisation with vaccine-type pneumococci and S aureus, which might explain the increase in S aureus-related otitis media after vaccination.
Acute Disease↗
Perioperative pharmacokinetics of cefotaxime in serum and bile during continuous and intermittent infusion in liver transplant patients.
BACKGROUND: Drug pharmacokinetics may be altered during liver transplantation. Cefotaxime (CTX), used as perioperative prophylaxis, demonstrates time-dependent killing and therefore continuous infusion might have pharmacodynamic advantages. OBJECTIVES: To determine the pharmacokinetics of CTX and desacetylcefotaxime (DCTX) in serum, bile and urine during continuous and intermittent infusion when performing liver transplantation. METHODS: Fifteen patients undergoing liver transplantation were studied after continuous infusion (CI) (4000 mg iv per 24 h following a loading dose of 1000 mg) and intermittent bolus infusion (BI) (1000 mg iv four times daily). Samples were collected during the first 48 h after liver transplantation. Concentrations of CTX and DCTX were determined by HPLC. RESULTS: During surgery, the mean concentration in serum after CI was 18 mg/L. The lowest serum concentration was 5 mg/L in the CI group and levels were undetectable in the BI group. Target serum concentrations of > or =4 mg/L were reached for 100% of the dosing interval during CI and approximately 60% during BI. Post-operatively, the mean concentration in serum after CI was 26 mg/L. The lowest serum concentration was 8 mg/L in the CI group and levels were undetectable after BI. The peroperative pharmacokinetics of CTX in this patient group were deranged and variable, mainly caused by an increased volume of distribution and decreased hepatic clearance. Metabolism was hampered, but DCTX area under the curve (AUC)/CTX AUC ratios varying between 0.7-0.9 were reached peroperatively. Post-operatively, DCTX AUC/CTX AUC ratios were higher (1.1-1.4). Unchanged CTX in bile was approximately 0.1% of the administered dose, leading to concentrations >4 mg/L throughout the dosing interval for both regimens. CONCLUSION: Although an intermittent bolus infusion of CTX 1000 mg produces t > target concentration for 60% of the dosing interval during liver transplantation, serum concentrations may be insufficient during the reperfusion phase. Continuous infusion overcomes this. Post-operatively, CTX clearance is impaired by decreased metabolic clearance and there is substantial accumulation of DCTX. In bile, sufficient concentrations of CTX and its active metabolite are reached with both regimens.
Adult↗
[Outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in the Rijnmond region: the largest outbreak in the Netherlands].
UNLABELLED: EPIDEMIC: The annual number of new MRSA isolates in the Netherlands tripled in 2002 compared with previous years. This increase was in part due to a MRSA outbreak in the Rijnmond region. The outbreak occurred in two merged hospitals and is the largest ever to occur in the Netherlands. From November 2001 till June 2003 MRSA was isolated from 381 patients and 113 hospital employees. The worst affected departments were Surgery and Internal Medicine. One MRSA strain (pulsed-field gel electroforesis (PFGE) type 16) remained initially unrecognised and was therefore able to spread unnoticed. Soon two additional epidemic MRSA strains (types 37 and 38) were discovered. DISCUSSION: Multiple factors played a role in the extent and duration of the outbreak. Because of the delayed detection and rapid spread of MRSA type 16, the outbreak grew too large once recognised to be resolved within the available infrastructure. Investments were needed at various fields, including the infection-control service and the microbiology laboratory. Employees had to be informed and motivated, and a separate MRSA ward and OPD were provided. New MRSA outbreaks occurred, despite extensive MRSA (contact) screening among patients and employees. The numbers of isolates began falling as from the beginning of 2003.
Cross Infection↗
Accuracy of identification and susceptibility results by direct inoculation of Vitek 2 cards from positive BACTEC cultures.
Rapid identification of bacteria and prompt acquisition of susceptibility results are valuable for patient care. The objective of the present study was to determine the accuracy of direct inoculation of Vitek 2 cards from positive BACTEC cultures compared to inoculation of the cards from subculture plates. Positive BACTEC cultures sampled between March 2001 and June 2002 were included. The results of direct inoculation were compared with the results of inoculation of Vitek 2 cards from subcultures. Of 161 gram-negative bacilli, 129 (80%) were correctly identified by direct inoculation compared to 145 of 161 (90%) by subculture. Susceptibility testing was performed on 2,862 antibiotic-isolate combinations. The essential agreement was 98.7%. The number of very major, major, and minor errors was 1 (0.2% of resistant strains), 1 (0.04% of susceptible strains), and 68, respectively. Direct identification of Staphylococcus spp. was not performed, but antimicrobial susceptibility was tested using 6,042 antibiotic-isolate combinations. The essential agreement was 95.2%. The number of very major, major, and minor errors was 73 (4.5% of resistant strains), 32 (0.8% of susceptible strains), and 106, respectively. Eighty-four percent of the very major errors occurred with trimethoprim-sulfamethoxazole. The results show that direct inoculation of Vitek cards is valuable as a rapid routine method for identification and susceptibility testing of gram-negative bacilli. For Staphylococcus spp., the susceptibility results obtained after direct inoculation of Vitek 2 cards are also acceptable except for those obtained with trimethoprim-sulfamethoxazole. Susceptibility results for this antibiotic, if obtained using direct inoculation, should not be reported to the clinician.
Bacteremia↗
Low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission in the Netherlands: the value of search and destroy and restrictive antibiotic use.
In the Netherlands, less than 1% of clinical isolates of Staphylococcus aureus are methicillin-resistant (MRSA). A national search and destroy policy prevents MRSA from becoming endemic. Some MRSA outbreaks cannot be related to patients at risk for MRSA carriage. This study was designed to measure the prevalence of MRSA among patients without risk factors for MRSA carriage at the time of admission to the hospital. In four Dutch hospitals, patients admitted to non-surgical departments in the period 1999-2000 were screened for MRSA nasal carriage. Nasal swabs were streaked on 5% sheep blood agar (BA), submerged in a selective broth, and incubated for two to three days at 35 degrees C. Colonies suspected of being S. aureus were identified with an agglutination test. Susceptibility testing was performed by an automated system and additional oxacillin disk diffusion. Methicillin resistance was confirmed by a DNA hybridization test and mecA PCR. MRSA strains were genotyped by pulsed-field gel electrophoresis (PFGE). Twenty-four percent (2332/9859) of the patients were S. aureus nasal carriers. Only three (0.03%) patients were MRSA carriers. These patients were not repatriated, nor known to be MRSA carriers before screening. Genotyping revealed that the strains were not clonally related and were not related to MRSA outbreaks in the hospital where the patients were admitted. We conclude that at routine admission to a Dutch hospital (excluding high-risk foreign admissions) the MRSA prevalence is low (0.03%), due to the Dutch search and destroy policy and restrictive antibiotic prescribing.
Carrier State↗
Comparative evaluation of three chromogenic agars for detection and rapid identification of aerobic Gram-negative bacteria in the normal intestinal microflora.
OBJECTIVE: To compare three different chromogenic agars and MacConkey agar for the detection of aerobic Gram-negative bacteria in the normal intestinal microflora and to assess the accuracy of the chromogenic agars for the direct identification of Escherichia coli. METHODS: A total of 164 Gram-negative clinical isolates (E. coli, Proteus, Klebsiella, Enterobacter, Morganella and Pseudomonas species) and 30 stool specimens were inoculated in parallel on four media: Chromagar E. coli/Coliform, Chromogenic urinary tract infection UTI medium, CHROMagar Orientation and MacConkey agar. All colonies that differed by color and/or morphology were selected for further identification by VITEK 1 and/or API 20E from each medium. RESULTS: On E. coli/Coliform agar five out of 32 (16%) E. coli strains failed to produce the color as described by the manufacturer. No remarkable discrepancies were found for the other clinical isolates. There was no significant difference in detection rate (DR) of aerobic Gram-negative bacteria in stool specimens between the different chromogenic agars and MacConkey agar. The overall DR was about 84%, and varied from 100% for monomicrobial specimens to 33% for polymicrobial specimens. The positive predictive values (PPV) for the direct identification of E. coli on Chromagar E. coli/Coliform, Chromogenic UTI medium and CHROMagar Orientation were 1.00, 0.93 and 0.93, respectively. The negative predictive values (NPV) were 0.53, 0.68 and 0.69, respectively. CONCLUSION: Chromogenic UTI medium and CHROMagar Orientation are the preferred media because of the higher NPV. The high PPV of these agars allows accurate and rapid identification of E. coli.
Agar↗
Microbial population diversity in the urethras of healthy males and males suffering from nonchlamydial, nongonococcal urethritis.
Nonchlamydial, nongonococcal urethritis (NCNGU) is suggested to be a sexually transmitted disease in men. NCNGU patients were compared to control subjects with regard to the presence of potentially infectious bacteria in the first void urine. Patients' pre- and post-antibiotic-treatment urine samples and two samples obtained 2 weeks apart from healthy volunteers, who did not receive antibiotic therapy, were analyzed with broad-spectrum PCR tests aiming at eubacterial small subunit rRNA genes. Restriction fragment length polymorphism analysis of the amplicons cloned from the mixtures of PCR products revealed that many different species of microorganisms were found to be colonizing the male urethra. We document here clear differences in the composition of the resident urethral flora between samples obtained from various individuals and between samples obtained at various points in time for a single individual. No major changes in population complexity were found upon antimicrobial treatment. In two of five patients a previously suggested pathogen (Mycoplasma genitalium or Haemophilus parainfluenzae) was accurately identified on the basis of DNA sequencing. No ubiquitous, azithromycin-sensitive organism was identified as a common pathogen in all patients, but up to 40% of all clones represented as-yet-unclassified bacterial species. Relatively often Pseudomonas spp. or Pseudomonas-like organisms were identified in the bacterial flora of patients. Interestingly, an as-yet-uncharacterized microbial species was identified as a negative predictor of NCNGU. This species was identified in all control subjects and was absent from all of the patient' samples (5 of 5 versus 0 of 5, P = 0.0079). This suggests that NCNGU might also be diagnosed by assessing the absence rather than the presence of certain bacterial species.
Adult↗
Mapping antibiotic use and resistance in the Netherlands: SWAB and NethMap.
The worldwide emergence of antimicrobial resistance has elicited responses from national and international organisations, including the World Health Organisation and the European Union. In the Netherlands, the non-profit foundation SWAB was jointly started by several professional medical societies to coordinate the Dutch efforts in preventing and reversing the trend of emerging resistance. SWAB publishes guidelines on the prudent use of antibiotics in this and other journals. The results of SWAB's surveillance systems for antibiotic consumption and resistance were recently summarised in its NethMap 2003 document. Attention should now be focused on elucidating the major determinants of antibiotic use and resistance emergence, and designing effective intervention strategies to reverse the trend of resistance emergence.
Anti-Bacterial Agents↗
Experience with a once-daily dosing program of aminoglycosides in critically ill patients.
BACKGROUND: As aminoglycosides show concentration-dependent killing, once-daily aminoglycoside (ODA) regimens have been instituted. Data on experience with ODA regimens in critically ill patients are limited. OBJECTIVES: 1) To evaluate the ODA-program in critically ill patients; 2) to describe the pharmacokinetics of aminoglycosides (gentamicin and tobramycin); and 3) to assess the incidence of nephrotoxicity associated with an ODA regimen in this specific of group patients. DESIGN: A prospective, descriptive study. SETTING: Eighteen-bed surgical and 12-bed medical intensive care unit in a referral centre. PATIENTS: Eighty-nine critically ill patients with a suspected or confirmed infection for which gentamicin or tobramycin was indicated and a creatinine clearance > 30 ml/min were monitored. One hundred and nine pharmacokinetic profiles were gathered. INTERVENTIONS: A first dose of 7 mg/kg/24 h of gentamicin or tobramycin was given to every patient independent of renal function. Subsequent doses were chosen on the basis of the pharmacokinetic results of the first dose. MEASUREMENTS: Serum samples were collected 1 h and 6 h after start of the aminoglycoside infusion. All samples were assayed by using immunofluorescence. Pharmacokinetic parameters were estimated using a one-compartment model. RESULTS: The volume of distribution of aminoglycosides was significantly higher in critical ill patients with septic shock than in those without. Consequently, the maximum concentration reached was significantly lower in patients with septic shock. In P. aeruginosa infections the mean (SD) estimated Cmax/MIC ratio was 10.3 (3.3). In n = 17 (49%) of the patients treated > 24 h ( n = 35), a dose adjustment or lengthening of interval was necessary. The recommended dosing interval based on the Hartford Hospital nomogram and one-serum concentration at 6 h was correct in only 62% of all cases. Signs of renal impairment occurred in n = 12 (14%) of the patients; in all survivors renal function recovered completely and no haemofiltration was needed. CONCLUSIONS: An ODA-regimen of 7 mg/kg produced Cmax/MIC ratios > 10 in the majority of critically ill patients in our population. Septic shock and renal dysfunction caused an aberrant pharmacokinetic profile of aminoglycosides in these patients. Therefore, individual therapeutic drug monitoring is warranted. Signs of renal impairment were common in the presence of shock, but appeared to be reversible.
Adult↗
Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intra-abdominal infections.
Ceftazidime demonstrates time-dependent killing, which is maximal at 4 x or 5 x MIC for the organism, consequently continuous infusion (CI) has been proposed to ensure adequate ceftazidime concentrations for the entire course of therapy. Severe intra-abdominal infections (IAIs) require surgical or percutaneous drainage for management, and ceftazidime is frequently prescribed. Cardiovascular or metabolic changes and renal or liver dysfunction may alter drug pharmacokinetics during severe IAIs, and no data exist on concentrations of ceftazidime reached in the peritoneal fluid. The objectives here were to determine the pharmacokinetics of ceftazidime during continuous and intermittent administration in patients with severe IAIs, and to measure the concentrations of ceftazidime in the peritoneal exudate. Eighteen surgical patients with severe IAI and a creatinine clearance of >30 mL/min were studied. A non-randomized pilot study of six patients treated with CI alone was followed by a prospective, randomized comparative study of 12 patients. Pilot study patients received ceftazidime 1 g iv followed by a 4.5 g CI over 24 h. Randomized patients received either ceftazidime continuously as above or 1.5 g tds. Samples for pharmacokinetic analyses were collected on days 2 and 4. Ceftazidime concentrations were determined by high-performance liquid chromatography. CI resulted in a mean serum concentration >40 mg/L and a T> 4 x MIC for most pathogens encountered in severe IAIs for >90% of the course of therapy in both serum and peritoneal exudate. Eight-hourly administration resulted in T> 4 x MIC for most pathogens encountered in severe IAIs for >90% of the dosing interval, but in peritoneal exudate for only 44% of the dosing interval. During CI, AUCs in the peritoneal exudate were c. 60% of the concomitant serum AUCs. In critically ill surgical patients with severe IAIs, CI of ceftazidime resulted in more favourable concentrations in serum and peritoneal exudate than 8-hourly bolus infusion.
Adult↗
Recombinant human activated protein C for severe sepsis.
Explore the source record for details and available documents.
Anti-Inflammatory Agents, Non-Steroidal↗
Pharmacokinetics of sequential intravenous and enteral fluconazole in critically ill surgical patients with invasive mycoses and compromised gastro-intestinal function.
OBJECTIVES: (1) To determine the pharmacokinetics of sequential intravenous and enteral fluconazole in the serum of surgical intensive care unit (ICU) patients with deep mycoses. (2) To determine the concentrations of fluconazole reached at the site of infection. (3) To determine if enteral administration of fluconazole, which has an important pharmaco-economic advantage, is justified in this specific patient group. DESIGN: Descriptive, sequential study as a part of a therapeutic drug monitoring programme. SETTING: Eighteen-bed surgical ICU in a referral centre. PATIENTS: Fourteen critically ill surgical patients with recent gastro-intestinal (GI) surgery and deep mycosis caused by a fluconazole-susceptible fungus and a calculated creatinine clearance of more than 40 ml/min. INTERVENTIONS: Fluconazole dosage regimen: 400 mg i. v. every 24 h with an extra dose of 400 mg i.v. after 12 h on day 1. If the clinical condition allowed enteral administration on day 4, the content of two capsules of 200 mg was given via the feeding tube with concomitant enteral feeds. MEASUREMENTS AND MAIN RESULTS: Serum, exudate from the site of infection and urine samples collected at assumed steady state ( after > or = 5 doses). Fluconazole concentrations were determined by high-performance liquid chromatography (HPLC). The mean area under the concentration curve (AUC0-24 h) in serum after enteral administration did not significantly differ from the AUC0-24 h during intravenous treatment. The elimination half-life was longer compared to healthy volunteers. The mean (95% CI) estimated bioavailability was 124 (90-158)%. The mean (95% CI) area under the concentration time curves (AUCs) achieved in the exudate from the site of infection were 67 (55-79)% of the AUCs reached in serum for both regimens. CONCLUSIONS: In critically ill patients with recent GI surgery and/or peritonitis the bioavailability of enteral fluconazole was adequate. The concentrations of fluconazole reached in exudate were lower than those in serum for both regimens, but adequate to treat most cases of deep mycoses in this specific patient group.
Antifungal Agents↗
Determinants of Staphylococcus aureus nasal carriage.
This article aims to review what is currently known of the host and bacterial factors determining S. aureus nasal carriage, including recent developments and future prospects.
Animals↗
A clinical study on the association of Trichomonas vaginalis and Mycoplasma hominis infections in women attending a sexually transmitted disease (STD) outpatient clinic.
Swabs from the posterior vaginal fornix were obtained from 804 consecutive female patients visiting a large Dutch sexually transmitted diseases (STD) outpatient clinic. A detailed clinical history was obtained and complaints concerning the lower genital tract, such as vaginal discharge or vulval and vaginal irritation, were recorded. Patients were examined and the presence of non-physiological vaginal secretions was established by speculum examination. The swabs were monitored for bacterial vaginosis (BV) or Candida albicans infection. PCR diagnosis of Chlamydia trachomatis and Trichomonas vaginalis was performed as well. Four groups of patients (n=14-21) with BV or single infections caused by one of these three pathogens and a control group with no pathogens were selected and Mycoplasma hominis PCR was performed additionally. At clinical presentation, controls and single-infected patient groups were comparable with regard to complaints of the lower genital tract and sexual risk behavior defined as having prior STDs and/or admitted prostitution. Only in the T. vaginalis-positive group significantly more women reporting sexual risk behavior were found than in controls. In agreement with former in vitro observations, an in vivo association between the PCR-detected presence of M. hominis and T. vaginalis was established. In 79% of all samples positive for T. vaginalis, M. hominis could be detected, as compared to only 6% in control samples (P=0.0004). However, since single infections by either of the two pathogens were regularly observed, there does not seem to be an exclusive association between the species, as the bacterium is also more frequently found in cases of BV (P=0.026). Co-infection of M. hominis with C. albicans (11%) or C. trachomatis (0%) did not differ significantly from controls (6%). M. hominis did not associate with complaints of the lower genital tract. However, if all groups were combined there appears to be a very significant association between the presence of M. hominis and sexual risk behavior (P=0.0004). M. hominis and sexual risk behavior were more closely associated than M. hominis and T. vaginalis. No indications were found for an enhanced pathogenicity by either of the symbionts.
Ambulatory Care↗