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Biomedical subjects

J A Kluytmans

Publications and source records attributed to J A Kluytmans.

At least 19 recordsLinked to original sources

Hickman catheter-related infections in neutropenic patients: insertion in the operating theater versus insertion in the radiology suite.

PURPOSE: To determine the influence of microbial air quality during Hickman catheter insertion in the operating theater versus insertion in the radiology suite on the incidence of catheter-related infections (CRIs). PATIENTS AND METHODS: Hemato-oncologic patients with prolonged neutropenia on antimicrobial prophylaxis were entered onto the study. Catheters were inserted by experienced radiologists under sonographic and fluoroscopic guidance. RESULTS: Forty-eight Hickman catheters in 39 patients were inserted (23 in the operating theater, 25 in the radiology suite). CRIs were seen in 16 catheters (33%; six per 1,000 catheter days; eight in each group). Local infections were found in nine catheters (22%; six in the operating theater v three in the radiology suite; not significant [NS]), catheter-related bacteremia was found in 10 (29%; three in the operating theater v seven in the radiology suite; NS). Coagulase-negative staphylococci (CoNS) caused all CRIs. Despite early vancomycin therapy, 11 (69%; four in the operating room group v seven in the radiology suite group; NS) of the catheters with CRIs had to be removed prematurely. At 90 days after insertion, catheter survival was 78% and 60% (NS) for the operating room and radiology suite, respectively. Multivariate analysis showed that neutropenia increased the CRI risk 20-fold (P =.004) and was strongly related to premature catheter removal owing to infection (relative risk = 11.9; P =.009). Neutropenia on the day of insertion was also significantly correlated with CRI (P =.04) and premature catheter removal owing to infection (P =.03). Serial cultures of blood, exit site, and catheter hub did not predict the development of CRI. CONCLUSION: The high incidence of Hickman CRI caused by CoNS was not associated with insertion location (operating theater v radiology suite). Neutropenia, including neutropenia on the day of insertion, was a significant risk factor for CRI and infection-related catheter removal.

Adult

Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in ICU patients with severe gram-negative intra-abdominal infections.

BACKGROUND: Few data are available on the pharmacokinetics of multiple enteral dosing of ciprofloxacin in critically ill intensive care patients and none for those with severe gram-negative intra-abdominal infections (GNIAI). OBJECTIVE: To determine the bioavailability of enteral ciprofloxacin in tube-fed intensive care patients with severe GNIAI. DESIGN: A randomized crossover study. SETTING: University-based medical center. PATIENTS: 5 critically ill intensive care patients with GNIAI and an estimated creatinine clearance > 25 ml/ min who received continuous tube feeding. INTERVENTIONS: Multiple doses of enteral 750 mg b.i.d. versus 400 mg b.i.d.i.v. ciprofloxacin. MEASUREMENTS: The calculated 12-h area under the serum concentration versus time curve after 750 mg b.i.d. enteral dosing was equivalent to that after 400 mg b.i.d.i.v. The mean bioavailability of enteral dosing was 53.1% [95% confidence interval (CI) 43.5-62.8]. In seven additional patients, the mean serum steady-state concentration at 2 h after enteral administration was 3.9 microg/ml (95% CI 1.9-5.9), not significantly different from that found in the crossover study (p = 0.4). CONCLUSIONS: In tube-fed intensive care patients with severe GNIAI, the bioavailability of enteral ciprofloxacin is adequate.

Adult

Hepatitis B and hemodialysis: the impact of universal precautions in preventing the transmission of bloodborne viruses.

A detailed description is presented of the hemodialysis treatment for 6 weeks of a patient strongly positive for hepatitis B virus ([HBV], hepatitis B surface antigen, hepatitis B e antigen, HBV DNA), which was performed without any special precautions. All 59 patients potentially exposed to the HBV-positive patient, of whom 29 appeared fully unprotected by antibody, were followed for at least 9 months but remained negative. This illustrates the feasibility of following Universal Precautions instead of using exceptional procedures for one single agent.

Adult

Clonal expansion of Staphylococcus epidermidis strains causing Hickman catheter-related infections in a hemato-oncologic department.

The detailed analysis of 411 strains of coagulase-negative staphylococci (CoNS) obtained from 40 neutropenic hemato-oncologic patients (61 Hickman catheter episodes) on intensive chemotherapy is described. By random amplification of polymorphic DNA (RAPD) analysis, a total of 88 different genotypes were detected: 51 in air samples and 30 in skin cultures prior to insertion, 12 in blood cultures after insertion, and only 5 involved in catheter-related infections (CRI). Two RAPD genotypes of Staphylococcus epidermidis predominated, and their prevalence increased during patient hospitalization. At insertion, these clones constituted 11 of 86 (13%) CoNS isolated from air samples and 33 of 75 (44%) CoNS isolated from skin cultures. After insertion, their combined prevalence increased to 33 of 62 (53%) in catheters not associated with CRI and 139 of 188 (74%) in catheters associated with CRI (P = 0.0041). These two predominant S. epidermidis clones gave rise to a very high incidence of CRI (6.0 per 1,000 catheter days) and a very high catheter removal rate for CRI, 70%, despite prompt treatment with vancomycin. A likely source of S. epidermidis strains involved in CRI appeared to be the skin flora in 75% of cases. The validity of these observations was confirmed by pulsed-field gel electrophoresis (PFGE) of SmaI DNA macrorestriction fragments of blood culture CoNS isolates. Again, two predominant CoNS genotypes were found (combined prevalence, 60%). RAPD and PFGE yielded concordant results in 75% of cases. Retrospectively, the same two predominant CoNS clones were also found among blood culture CoNS isolates from the same hematology department in the period 1991 to 1993 (combined prevalence, 42%) but not in the period 1978 to 1982. These observations underscore the pathogenic potential of clonal CoNS types that have successfully and persistently colonized patients in this hemato-oncology department.

Air Microbiology

[Hospital Infection Epidemiology Nederland (ZIEN): from club to study group].

Medical care is increasingly a technical business, and hospitalised patients are more and more susceptible to infections, notably due to the application of aggressive therapies for all kinds of disorders. As a consequence the epidemiology of hospital infections requires serious attention. Following the initiative of some medical microbiologists in the Netherlands, a study group was established to tackle this epidemiology and to initiate relevant research (Working party on Hospital Infections and Epidemiology of the Netherlands; WHEN). Recent subjects include fungemia in hospitalised patients, risk factors for acquiring methicillin-resistant Staphylococcus aureus during a stay abroad, and prevalence of vancomycin-resistant enterococci.

Cross Infection

Fecal carriage of vancomycin-resistant enterococci in hospitalized patients and those living in the community in The Netherlands.

In order to determine the prevalence of vancomycin-resistant enterococci (VRE) in The Netherlands, 624 hospitalized patients from intensive care units or hemato-oncology wards in nine hospitals and 200 patients living in the community were screened for VRE colonization. Enterococci were found in 49% of the hospitalized patients and in 80% of the patients living in the community. Of these strains, 43 and 32%, respectively, were Enterococcus faecium. VRE were isolated from 12 of 624 (2%) and 4 of 200 (2%) hospitalized patients and patients living in the community, respectively. PCR analysis of these 16 strains and 11 additional clinical VRE isolates from one of the participating hospitals revealed 24 vanA gene-containing, 1 vanB gene-containing, and 2 vanC1 gene-containing strains. All strains were cross-resistant to avoparcin but were sensitive to the novel glycopeptide antibiotic LY333328. Genotyping of the strains by arbitrarily primed PCR and pulsed-field gel electrophoresis revealed a high degree of genetic heterogeneity. This underscores a lack of hospital-driven endemicity of VRE clones. It is suggested that the VRE in hospitalized patients have originated from unknown sources in the community.

Anti-Bacterial Agents

Detection of Chlamydia trachomatis in male and female urine specimens by using the amplified Chlamydia trachomatis test.

The amplified Chlamydia trachomatis test (AMP-CT; Gen-Probe), a new diagnostic test for the detection of Chlamydia trachomatis, was evaluated with urine specimens from 1,000 patients visiting the outpatient department for sexually transmitted diseases at the University Hospital Rotterdam, Rotterdam, The Netherlands, by comparing the results to those of cell culture. From February 1996 to July 1996, urine samples for the AMP-CT test and urethral swabs for cell culture were collected from 544 men, while cervical swabs from 456 women were also taken for cell culture. Positive test results were obtained for 130 (13%) of the patients. AMP-CT test and cell culture results were discordant for 70 (7%) specimens. Analysis of the samples with discordant results was performed by an in-house PCR. After resolution of the discordant results, the sensitivity, specificity, and positive and negative predictive values of the AMP-CT test were 84.3, 98.8, 89.6, and 98%, respectively, for samples from females and 100, 99.2, 93.1, and 100%, respectively, for samples from males, while for cell culture these values were 72.5, 99.2, 92.5, and 98%, respectively, for samples from females and 57.4, 99.0, 86.1, and 95.4%, respectively, for samples from males. We conclude that the AMP-CT test is a fast and reliable test for the detection of C. trachomatis in urine specimens from females and, in particular, males.

Bacteriuria

Occurrence of yeast bloodstream infections between 1987 and 1995 in five Dutch university hospitals.

The aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient days of care during the nine-year study period. The rate of candidemia doubled in the study period, reaching an incidence of 0.71 episodes per 10,000 patient days in 1995. The general increase in candidemia was paralleled by an increase in non-Candida albicans bloodstream infections, mainly due to Candida glabrata. However, more than 60% of the infections were caused by Candida albicans. Fluconazole-resistant species such as Candida krusei did not emerge during the study period. The increasing rate of candidemia found in Dutch university hospitals is similar to the trend observed in the USA, but the rate is lower and the increase is less pronounced.

Antifungal Agents

Vertebral bone destruction in sickle cell disease: infection, infarction or both.

Infectious and vaso-occlusive vertebral bone and joint destruction in two patients with sickle cell disease (SCD) are featured by H-shaped vertebrae, kyphotic angulation, osteolysis of endplates and collapse of intervertebral discs as shown by X-ray films and magnetic resonance imaging. Staphylococcal serology supported the diagnosis of staphylococcal osteomyelitis/spondylo-discitis in both SCD patients. The difficulties of establishing the causes and treatment of the osteoarthropathy in these particular cases are discussed in the light of the literature.

Adult

Reduction of surgical-site infections in cardiothoracic surgery by elimination of nasal carriage of Staphylococcus aureus.

OBJECTIVE: To test the hypothesis that perioperative elimination of nasal carriage of Staphylococcus aureus using mupirocin nasal ointment reduces the surgical-site infection (SSI) rate in cardiothoracic surgery. DESIGN: Unblinded intervention trial with historical controls. SETTING: A university hospital, tertiary referral center for cardiothoracic surgery. PATIENTS: Consecutive patients undergoing cardiothoracic surgery between August 1, 1989, and February 1, 1991 (historical control group), and between March 1, 1991, and August 1, 1992 (intervention group). RESULTS: The historical control group consisted of 928 patients and the intervention group of 868, of whom 752 actually were treated. The 116 patients who were unintentionally not treated were considered as a concurrent control group. In the intention-to-treat analysis, a significant reduction in SSI rate was observed after the intervention (historical-control group 7.3% and intervention group 2.8%; P < .0001). The SSI rate in the concurrent control group was significantly higher than in the treated group (7.8% and 2.0%, respectively; P = .0023). Resistance of S aureus to mupirocin was not observed. CONCLUSION: The results of this study indicate that perioperative elimination of nasal carriage using mupirocin nasal ointment significantly reduces the SSI rate in cardiothoracic surgery patients and warrants a prospective, randomized, placebo-controlled efficacy trial. This preventive measure may be beneficial in other categories of surgical patients as well.

Administration, Intranasal

Cost-effectiveness of perioperative mupirocin nasal ointment in cardiothoracic surgery.

OBJECTIVE: To assess the cost-effectiveness of perioperative intranasal application of mupirocin calcium ointment in cardiothoracic surgery. DESIGN: Cost-effectiveness analysis based on results of an intervention study with historical controls. SETTING: University Hospital Rotterdam, a tertiary referral center for cardiac and pulmonary surgery. PATIENTS: Consecutive patients undergoing cardiothoracic surgery between August 1, 1989, and February 1, 1991 (control group, n = 928), and between March 1, 1991, and August 1, 1992 (intervention group, n = 868). INTERVENTION: Perioperative nasal application of mupirocin calcium ointment started on the day before surgery, continued for 5 days, twice daily. RESULTS: Postoperative costs were increased significantly in patients with a surgical-site infection (SSI), compared with uninfected patients (P < .001). Mean SSI-attributable costs were estimated at $16,878 (95% confidence interval, $15,575-$18,181). The incidence of SSIs was 7.3% in the control group and 2.8% in the intervention group, mupirocin effectiveness being 62%. The costs of mupirocin were $11 per patient. Thus, the savings per SSI prevented were $16,633. To validate this comparative estimate of SSI-attributable costs, a noncomparative analysis of the postoperative length of stay (POLS) was performed, according to the Appropriateness Evaluation Protocol. Approximately 50% of the comparative SSI-attributable POLS were judged SSI-attributable in the noncomparative analysis. Sensitivity analyses, testing for the robustness of our conclusions, indicated that the presented model is rather insensitive to variations in the incidence of SSIs and for the effectiveness and costs of mupirocin. SSI-attributable costs were shown to be the only variable with substantial effect on the cost-effectiveness ratio. Perioperative mupirocin would result in net costs instead of savings only if SSI-attributable costs were less than $245. CONCLUSIONS: SSIs in patients undergoing cardiothoracic surgery are associated with a substantial increase in postoperative costs. Provided that perioperative mupirocin reduces the SSI rate, this measure will be highly cost-effective in most centers providing cardiothoracic surgical services.

Administration, Intranasal

Elimination of nasal carriage of Staphylococcus aureus in hemodialysis patients.

OBJECTIVE: To study the efficacy of mupirocin for the elimination of nasal carriage of Staphylococcus aureus in hemodialysis patients. DESIGN: The efficacy of mupirocin was studied in a prospectively followed cohort. The effect of this intervention on the rate of S aureus bacteremia was evaluated using a historic control group. SETTING: Patients on the hemodialysis unit of the University Hospital Rotterdam, a tertiary referral center. PATIENTS: The study group consisted of consecutive patients on hemodialysis from February 1, 1992, until November 1, 1993. They were screened by taking nasal cultures monthly during their time on hemodialysis. If S aureus was isolated, treatment with mupirocin nasal ointment was initiated. The control group consisted of patients treated on the same hemodialysis unit from January 1, 1990, until January 1, 1992. RESULTS: The study group consisted of 226 patients, of whom 172 were evaluated to determine the efficacy of mupirocin. Sixty-seven (39%) were identified as nasal carriers. Following the initial treatment, 66 nasal cultures (98.5%) became negative. After 3 months and 6 months, respectively, 63 (94%) and 61 (91%) of the treated carriers had negative cultures. The rate of bacteremia (defined as the number of episodes of S aureus bacteremia per patient-year on hemodialysis) was significantly lower among the 226 patients in the study group (0.04 per patient-year) than among the 273 patients in the control group (0.25 per patient year, P < .001). Development of resistance and adverse effects were not observed. CONCLUSIONS: Mupirocin nasal ointment effectively eliminates nasal carriage of S aureus in patients on hemodialysis. This was associated with a significant reduction of the incidence of S aureus bacteremia, as compared to historic controls.

Administration, Intranasal

Delta APACHE II for predicting course and outcome of nosocomial Staphylococcus aureus bacteremia and its relation to host defense.

To predict at an early phase the clinical course and outcome of nosocomial Staphylococcus aureus bacteremia, the APACHE II score at onset of bacteremia was calculated in 99 patients. A delta APACHE II score (i.e., the difference between this score and one calculated for the day before the bacteremia) was also determined. This delta APACHE II score was highly significantly correlated with clinical course (P<.001) and outcome (P<.001). The risk of a complicated clinical course and of dying from S. aureus bacteremia is determined at the very onset of bacteremia, and this risk can best be assessed by calculating the delta APACHE II score. Furthermore, a positive correlation was found between delta APACHE II scores and the level of serum opsonic activity (P=.003) toward S. aureus. Therefore, the complicated clinical course of S. aureus bacteremia is not due to a relative lack of specific opsonins.

APACHE

Exogenous pulmonary surfactant as a drug delivering agent: influence of antibiotics on surfactant activity.

1. It has been proposed to use exogenous pulmonary surfactant as a drug delivery system for antibiotics to the alveolar compartment of the lung. Little, however, is known about interactions between pulmonary surfactant and antimicrobial agents. This study investigated the activity of a bovine pulmonary surfactant after mixture with amphotericin B, amoxicillin, ceftazidime, pentamidine or tobramycin. 2. Surfactant (1 mg ml-1 in vitro and 40 mg ml-1 in vivo) was mixed with 0.375 mg ml-1 amphotericin B, 50 mg ml-1 amoxicillin, 37.5 mg ml-1 ceftazidime, 1 mg ml-1 pentamidine and 2.5 mg ml-1 tobramycin. Minimal surface tension of 50 microliters of the mixtures was measured in vitro by use of the Wilhelmy balance. In vivo surfactant activity was evaluated by its capacity to restore gas exchange in an established rat model for surfactant deficiency. 3. Surfactant deficiency was induced in ventilated rats by repeated lavage of the lung with warm saline until PaO2 dropped below 80 cmH2O with 100% inspired oxygen at standard ventilation settings. Subsequently an antibiotic-surfactant mixture, saline, air, or surfactant alone was instilled intratracheally (4 ml kg-1 volume, n = 6 per treatment) and blood gas values were measured 5, 30, 60, 90 and 120 min after instillation. 4. The results showed that minimal surface tensions of the mixtures were comparable to that of surfactant alone. In vivo PaO2 levels in the animals receiving ceftazidime-surfactant or pentamidine-surfactant were unchanged when compared to the surfactant group. PaO2 levels in animals receiving amphotericin B-surfactant, amoxicillin-surfactant or tobramycin-surfactant were significantly decreased compared to the surfactant group. For tobramycin it was further found that PaO2 levels were not affected when 0.2 M NaHCO3 (pH = 8.3) buffer was used for suspending surfactant instead of saline. 5. It is concluded that some antibiotics affect the in vivo activity of a bovine pulmonary surfactant. Therefore, before using surfactant-antibiotic mixtures in clinical trials, interactions between the two agents should be carefully evaluated.

Animals

Detection of PCR inhibitors in cervical specimens by using the AMPLICOR Chlamydia trachomatis assay.

To determine that susceptibility of AMPLICOR Chlamydia trachomatis PCR to inhibitory factors possibly present in cervical specimens, we obtained cervical specimens from 200 gynecology patients attending our outpatient clinic. The prevalence of C. trachomatis infection was 4.1%, as determined by cell culture. All AMPLICOR specimens were tested in one procedure as described by the manufacturer, and after the specimen was spiked with C. trachomatis, several other pretreatment protocols were used. Complete inhibition of the PCR was observed in 38 (19%) cervical specimens. Heat treatment at 95 degrees C, freeze-thawing, or 10-fold dilution of the samples reduced the initial inhibition to 9, 16, or 9%, respectively. A combination of heat treatment and 10-fold dilution reduced the inhibition to 4% of the samples. A second specimen type (swabs inoculated in 0.2 M sucrose phosphate buffer [2SP]) was also evaluated. A 10-fold dilution of the spiked 2SP specimen resulted in an inhibition rate of 6%, which was comparable to that obtained by centrifugation of the 2SP specimen prior to processing. Furthermore, it was shown that the inhibition was not correlated with blood contamination. Processing the specimens on the day of collection or the day after resulted in a higher inhibition rate than did delayed processing (27.6 versus 15.5%, respectively). An inverse correlation was found between the concentration of C. trachomatis added to the sample and the rate of inhibition observed. The inhibition was partly correlated with the pH of the cervical mucosa. Decreased inhibition was found at pH values of > or = 7.5. The effects of blood, pH, and delay in processing were all evaluated by using the AMPLICOR specimen. We conclude that the susceptibility of AMPLICOR C. trachomatis PCR to inhibiting factors in cervical specimens can be significantly reduced if the pretreatment procedure includes heat treatment or the use of 2SP transport medium. Also, a 10-fold dilution of the clinical specimen followed by heat treatment will largely prevent the inhibition of this PCR.

Cervix Uteri