Predictions for existing chemicals-a multilateral QSAR project.

Abstract Following a previous collaborative EU/EPA project focussed on QSAR predictions for a selection of new chemicals which had been notified in the EU, a similar exercise was started in 1993 on existing chemicals. In a first phase, the project addresses the High Production Volume (HPV) chemicals which are produced or imported at levels above a 1000t/year in the EU and 454t/year in the US. The relevant EU (Annex 1 of Existing Chemicals Regulation No. 793/93) and US-EPA lists contain 1036 and 2881 organic substances respectively of which HPV 749 chemicals are in common. The joint project aims at an estimation through validated QSAR models of the physical-chemical, ecotoxicity and toxicity endpoints which are included in the regulation and where experimental data will become available in IUCLID (International Unified Chemicals Information Database). Next to EC-JRC (ECB) and US-EPA, various laboratories in the EU are contributing to the project and recently, two institutes in Japan have joined in this project.

Trace element reference values in tissues from inhabitants of the European Union. VIII. Thallium in the Italian population.

In order to establish reference values of thallium in tissues of the general population the element was determined in blood (TlB) and urine (TlU) of 123 healthy inhabitants living in the Marche region, Central Italy. The analysis was carried out by inductively coupled plasma-mass spectrometry (ICP-MS; detection limit in our experimental conditions, 0.001 micrograms Tl/I), which was validated by neutron activation analysis (NAA) and laser induced fluorecence (LIF) spectroscopy. The check of pre-analytical factors indicated a low risk of contamination and loss of Tl during sampling, handling and storage before the instrumental analysis (blank of the entire procedure less than the detection limit). Mean values of TlU and TlB were 0.066 micrograms Tl/l and 0.063 micrograms Tl/l, respectively (median in both cases 0.057 microgram Tl/l). No conclusive evidence concerning the distribution followed by our data set, normal or log-normal, were drawn, although Lilliefors test and Kolmogorov's D-test showed a tendency for TlB to follow both the normal and the log-normal while TlU followed a log-normal distribution. Overall correlations between TlU and TlB are rather weak. A significant, but not high, correlation (P < 0.0004, r = 0.44) was observed in females. Age, sex, smoking habits and alcohol consumption did not seem to play any role on TlU and TlB. Tentatively proposed reference intervals are 0.019-0.17 microgram Tl/l (urine) and 0.014-0.19 microgram Tl/l (blood).

[Peritonitis with continuous ambulatory peritoneal dialysis. Status and future perspectives]. / Peritonitis ved kontinuerlig ambulant peritoneal dialyse. Status og fremtidsperspektiver.

Peritonitis remains the major complication of continuous ambulatory peritoneal dialysis. A review is given of the clinical, microbiological, immunological, and pathogenic aspects of this problem and new fields of research for reducing the incidence of peritonitis are suggested.

Per-operative antibiotic treatment in cardiovascular surgery: the influence of methicillin versus cephalothin on post-operative infections and bacterial colonization.

This paper reports the results of a prospective study of antibiotic prophylaxis in 543 patients undergoing open-heart surgery. All patients were given per-operatively either methicillin, 1 g four times a day, or cephalothin, 1 g four times a day. There was no significant difference in the frequency of postoperative infections between the two groups. It was established that per-operative antibiotic prophylaxis selected resistant coagulase-negative staphylococci (CNS) in the nasal flora of cardiac surgery patients, that this change occurred to the same degree whether methicillin or cephalothin was used, that cephalothin favoured colonization with antibiotic resistant species other than CNS. It was found that the staff of the intensive care unit formed a reservoir of multi-resistant CNS.

An investigation of a collection of yellow-pigmented Pseudomonas.

Thirty-six strains of yellow-pigmented Pseudomonas from clinical as well as non-clinical material and 11 reference strains of Pseudomonas were investigated by means of conventional bacteriological methods (a total of 53 different tests). Eighteen of the 36 yellow-pigmented strains could be classified as P. paucimobilis. Apart from the presence of lipid inclusions on beta-hydroxybutyrate, hydrolysis of DNA, and Tween 80 our results showed a high degree of accordance with other investigations. Eight strains showed characteristics compatible with inclusion in the CDC VE group; one orange-yellow strain showed the characteristics of P. vesicularis, and one was a pyoverdin negative, yellow P. putida. Eight strains remained unidentified. Strains of P. paucimobilis were most often resistant to antibiotics used for P. aeruginosa infections (viz. piperacillin, cefsulodin, ceftazidime) while the strains of the CDC VE group were often susceptible. Most strains were susceptible to the aminoglycosides. The difficulties in distinguishing yellow-pigmented strains of Pseudomonas from Flavobacterium spp. or Xanthomonas spp. are discussed.

Consumption of antibiotics in three clinical departments and antimicrobial susceptibility of clinically significant isolates of coagulase-negative Micrococcaceae.

A total of 67 clinically significant isolates of coagulase-negative Micrococcaceae originating from blood specimens from oncologic patients, from dialysate from patients on peritoneal dialysis, and from cerebrospinal fluid from neurosurgical patients with ventricular drainage devices were identified and classified 1) according to the scheme of Baird-Parker and 2) by means of a simplified Kloos and Schleifer nomenclature. All blood isolates were classified as Staphylococcus epidermidis biotype 1 (Baird-Parker), while approximately 20% of dialysate isolates and cerebrospinal fluid isolates fell into other staphylococcal biotypes or were classified as micrococci. Using the simplified Kloos and Schleifer nomenclature, five staphylococcal isolates (8%) (four from dialysate, one from cerebrospinal fluid) were classified as "Species other than S. epidermidis". Isolates from blood exhibited a high frequency of resistance to the antibiotics tested, and 92% were found multiple-resistant (i.e. were resistant to three or more antibiotics). Isolates from cerebrospinal fluid showed multiple-resistance in 28%, while isolates from dialysate formed an intermediate group, 42% being multiple-resistant. The frequency of multiple-resistance was found to be correlated to the total consumption of antibiotics in the three clinical departments.

Population analysis of susceptibility to cefotaxime and desacetyl-cefotaxime in Staphylococcus and Enterobacteriaceae.

Population analyses of susceptibility to cefotaxime (CTX) and desacetyl-cefotaxime (DCTX) of strains of Staphylococcus and some genera of Enterobacteriaceae were carried out. DCTX, which is the main metabolite of CTX, has antimicrobial activity. The penicillinase-producing strains of S. aureus and S. epidermidis were homogeneous as regards susceptibility to both agents. CTX was about 4-8 times more active than DCTX. The methicillin-resistant strains contained a sub-population of resistant bacteria with both CTX and DCTX. The frequency of resistant bacteria was 10(-6) - 10(-5). The E. coli strain was homogeneous to both agents. The strains of Enterobacter cloacae and Citrobacter freundii had a sub-population of resistant bacteria with both agents. The frequency of resistant bacteria was 10(-7) - 10(-4.5). In Klebsiella pneumoniae no resistant sub-population was found. CTX was about four times more active than DCTX with the strains of the Enterobacteriaceae. DCTX had no advantage over CTX as regards homogeneity of susceptibility of the populations examined. CTX seems applicable for treatment of infections with E. coli, Klebsiella pneumoniae, and penicillinase-producing, methicillin-susceptible Staphylococcus, but should not be used alone in treatments of infections with Enterobacter cloacae or Citrobacter freundii.

Studies on coagulase-negative staphylococci in patients undergoing cardiac surgery. Different hypotheses for the origin of multiply-resistant isolates.

Hypotheses for the origin of multiply-resistant coagulase-negative staphylococci from 146 patients undergoing cardiac surgery were tested. All received cephalothin per-operatively. Antibiotic susceptibility testing, phage-typing, bio-typing, and test for Tween-80-splitting enzyme were used to characterize 132 isolates from nose swabs. Seventy-five percent of the pre-operative susceptible isolates were of biotype 1, while biotypes 3 and 4 made up 59% of the post-operative, multiply-resistant isolates. Fifty-three percent of the isolates were typable by phage-typing. Typability of isolates of biotype 1 was high (56%) while almost 75% of biotype 4 were untypable. Susceptible isolates were more often typable than multiply-resistant ones. Of the 146 patients, 105 (72%) carried coagulase-negative staphylococci pre-operatively, only two of them carried multiply-resistant strains. Fifty-nine patients (41%) were colonized with multiply-resistant coagulase-negative staphylococci post-operatively. By combining the results of bio-typing, phage-typing, and test for Tween-splitting enzyme the study made it probable that a maximum of ten patients (6.8%) already carried multiply-resistant strains on admission to the hospital or were carriers of initially susceptible strains which developed multiple-resistance during administration of antibiotics. It therefore seemed likely that most of the patients were deprived of their natural bacterial flora by antibiotic treatment and subsequently colonized post-operatively with multiply-resistant coagulase-negative staphylococci from the environment.

Etiologic importance of coagulase-negative Micrococcaceae isolated from blood cultures.

Coagulase-negative Micrococcaceae from blood cultures were classified biochemically according to Baird-Parker and to Kloos & Schleifer and by means of antibiotic susceptibility testing, in an attempt to distinguish between bacterial growth due to contamination and growth due to bacteremia. S. epidermidis biotype 1 (according to Baird-Parker) accounted for c. 60% of the isolates and for c. 85% of the isolates considered to be of clinical importance. The more time- and resource-demanding classification of Kloos & Schleifer provided no further clinically useful information, as the predominant number of isolates turned out to be S. epidermidis. Isolates other than S. epidermidis (according to Kloos & Schleifer) accounted for c. 45% of the total number of isolates but for only 20% of the isolates considered of clinical importance. Resistance to multiple antibiotics was recorded more often in isolates from patients with positive clinical information than in isolates thought to be contaminators. The frequency of blood cultures contaminated with coagulase-negative Micrococcaceae was estimated at c. 1.5%. Records from 91 patients were reviewed. By correlating the clinical findings to biochemical classification, resistance types, and the massiveness of growth it was suggested that the quantitative rather than the qualitative findings are suitable for determining clinical significance of isolates of coagulase-negative Micrococcaceae from blood cultures.

Population analysis in strains of Staphylococcus aureus and Staphylococcus epidermidis. II. Cefuroxime and cefotaxime.

Population analyses of susceptibility to cefuroxime and cefotaxime in penicillin-susceptible, penicillin-resistant, and methicillin-resistant strains of Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) were carried out. All strains were clinical isolates. Both antibiotics were shown to be more penicillinase-stable than cephalothin in studies of the penicillin-resistant strains of S. aureus, but less stable than methicillin. The studies of penicillin-resistant strains of S. epidermidis showed no differences in penicillinase-stability between cephalothin and the new cephalosporins. From the methicillin-resistant strains of S. aureus and S. epidermidis it was possible to select highly-resistant mutants against both antibiotics with a frequency of c. 10(-5) although MIC determinations had shown the strains to be susceptible.

Population analysis of susceptibility to methicillin, vancomycin, and three cephalosporines in two methicillin-resistant strains of Staphylococcus epidermidis.

Population analyses of susceptibility to methicillin, vancomycin, cephalothin, cefamandole, and cefoxitin were carried out with two strains of Staphylococcus epidermidis (S. epidermidis) resistant to penicillin, streptomycin, and methicillin. Two strains of Staphylococcus aureus (S. aureus), one sensitive to penicillin the other resistant, were used as controls. All strains were clinical isolates. From the strains of S. epidermidis it was possible to select sub-populations highly resistant to methicillin, cephalothin, cefamandole, and cefoxitin. The mutation-rate varied between c. 10(-3) and 10(-7). The two strains were homogeneous as regards vancomycin susceptibility. Methicillin was shown to be more penicillinase-stable than the cephalosporines. Treatment in vivo, with cephalothin and vancomycin did not increase the frequency of highly resistant bacteria against any of the antibiotics, but during treatment with cephalothin the majority-population became eight times more resistant to vancomycin and may explain why the treatment in vivo was not successful.

Investigation of Micrococcaceae in a department of cardiac surgery. Biochemical characterization and sensitivity patterns of strains isolated from patients, staff, and air.

A total of 965 strains of Micrococcaceae isolated from 200 patients, personnel, and air in a department of cardiac surgery were classified by means of Baird-Parker's scheme. The majority of strains were identified as Staphylococcus epidermidis (S. epidermidis) biotype 1, but S. epidermidis biotype 4 accounted for c. 25% of isolates from patients post-operatively. Pre-operative isolates were generally sensitive to most antibiotics tested while post-operative strains of coagulase-negative Micrococcaceae from patients and isolates from personnel and air were frequently multiply-resistant. Strains of Staphylococcus aureus (S. aureus) were sensitive or resistant only to penicillin. More patients were colonized with coagulase-negative Micrococcaceae after operation than at admission to the hospital (p less than 0.001), while the frequency of S. aureus carriers was the same before and after operation and equal to the frequency found earlier. The frequency of S. aureus carriers among the personnel, however, was lower than reported earlier (10%). Multiply-resistant strains of S. epidermidis seem to have replaced resistant strains of S. aureus as the predominant hospital saprophyte among Micrococcaceae.

The occurrence of Staphylococcus epidermidis in a department of thoracic and cardiovascular surgery. A clinical and epidemiological investigation.

Changes in resistance traits of Staphylococcus epidermidis isolated in the preoperative and postoperative phases from patients undergoing open heart surgery were studied in a two-step prospective investigation. Period 1 comprised 32 patients. All received streptomycin for five days and methicillin for seven days, starting the evening before operation. None of the patients was colonized with multiresistant (MR) strains before or immediately after operation. Two days after operation, in the intensive care unit (ICU) 79% of the patients carried MR S. epidermidis in the nose. Air analyses showed that 30% of the bacteria isolated from the ICU were MR, while such strains were seldom found in the operating theatre. Nose swabs from the staff showed that 26% at the ICU and none in the operating theatre carried MR strains. In an attempt to counteract the selection for MR strains, all patients in period 2 received methicillin alone for only 3 days, and disinfection of the ICU was then performed after each patient. Period 2 comprised 105 patients. The frequency of MR S. epidermidis in the patient material declined from 80% to 40% and from 26% to 15% in the staff members. No changes were found concerning the frequency of postoperative complications. The conclusion is that methicillin alone for three days gives as good a protection against postoperative infections as a more broad-spectrum treatment and that reduced use of antibiotics will reduce the risk of early colonization with resistant strains.