Assessment of the depth of anesthesia based on symbolic dynamics of the EEG.

Methodologies based on symbolic dynamics have successfully demonstrated to reflect the nonlinear behavior of biological signals. In the present study, symbolic dynamics was applied to the electroencephalogram (EEG) in order to describe the level of depth of anesthesia. The EEG was transformed to symbol sequences. Words of three symbols were built from this symbolic series. The results obtained from the EEGs of 36 patients undergoing anesthesia showed that the probabilities of the word types were able to reflect the depth of anesthesia in a similar way to the auditory evoked potential index AAI, a commercial index.

Depth of anesthesia index using cumulative power spectrum.

Over the last ten years, monitors of depth of anesthesia have progressively been integrated in the clinical practice. Based on the analysis of the electroencephalogram (EEG), these monitors deliver an index that helps the anesthesiologist to determine the state of the patient during the surgery. Although they employ different kind of algorithms, spectral parameters are always taken into account to achieve the final indexes. In this work, a new spectral parameter based on the cumulative power spectrum is proposed. When compared to the Spectral Edge Frequency (SEF), a classic spectral parameter, the Cumulative Power Spectrum Index (CPSI) presents a higher correlation with reference indexes (AAI, BIS and CePROP) and a higher prediction probability of the state of the patient. Furthermore, when compared to the reference indexes, the CPSI shows similar performances in terms of correlation and presents a higher prediction probability than two of them (BIS and CePROP).

A new method for evaluating the performance of depth-of-hypnosis indices - the D-value.

An alternative statistic, the D-value, is presented for the evaluation of the performance of EEG-based depth-of-hypnosis measures against the Observers' Assessment of Alertness/Sedation scale. The measures considered here are spectral entropy, approximate entropy, Lempel-Ziv complexity and Higuchi fractal dimension. The study is based on recordings from 45 patients, divided into three groups of 15 recordings each. Patients of Group I received no remifentanil while patients of Groups II and III received 2 and 4 ng/ml effect compartment controlled remifentanil. All the patients received stepwise increased dose of propofol. The study shows that the D-value is a promising and flexible statistic for the evaluation of the discriminative power of the EEG measures with respect to the OAA/S scale. The D-value indicates well the dependence of the performance of the measures on the EEG frequency band as well as on remifentanil concentration.

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.

Kinetics of anti-mannan antibodies useful in confirming invasive candidiasis in immunocompromised patients.

In studying the anti-mannan antibodies longitudinally in serial serum samples of three immunocompromised patients, it was observed that anti-mannan antibodies started to increase shortly after the moment that cultures of deep-tissue sites became positive with Candida albicans. The mean anti-mannan antibody titers determined in a group of 36 immunocompromised patients with invasive candidiasis increased within two weeks after the probable onset of invasive candidiasis. In contrast, anti-mannan antibody levels in serial serum samples of 14 immunocompromised patients who were only colonized with C. albicans remained stable or decreased over time. The HA test measuring the anti-mannan antibodies was 64% sensitive and 89% specific in determining invasive candidiasis. In contrast, antibodies specific for candidal cytoplasmic antigens or enolase alone were of little value in confirming invasive candidiasis in these immunocompromised patients.

Chlamydia trachomatis-specific antibodies in patients with pelvic inflammatory disease: comparison with isolation in tissue culture or detection with polymerase chain reaction.

OBJECTIVE: The detection of acute phase antibodies against C trachomatis and its comparison with tissue culture or polymerase chain reaction (PCR) on samples of cervix and urethra obtained from patients with pelvic inflammatory disease (PID). METHODS: In the academic hospital Dijkzigt, Rotterdam, The Netherlands, prospective investigations were performed on 49 consecutive patients who were admitted with the diagnosis of PID. Infections with C trachomatis were traced using tissue culture, PCR or by determining acute phase IgG and IgM antibodies. Differences between the sensitivities of serology and tissue culture or PCR were calculated using the Fisher exact test. RESULTS: C trachomatis infection was detected more often in PID patients using serology in comparison with PCR (p < 0.05) or tissue culture (p < 0.05). All patients who were positive in tissue culture also had acute phase antibodies. CONCLUSION: The establishing of acute C trachomatis infections in PID patients on the basis of serology was superior to either tissue culture or PCR on samples obtained from cervix and urethra.

In vitro development and stability of tolerance to cloxacillin and vancomycin in Staphylococcus aureus.

The stability of tolerance of Staphylococcus aureus during subculturing at 37 degrees C and development of this property after repeated exposure to cloxacillin or vancomycin were investigated in vitro. Four of five tolerant strains lost this property during repeated subculturing at 37 degrees C for 50 days. Conversely, tolerance emerged in two of four nontolerant strains after repeated cycles of exposure to 25 micrograms of cloxacillin/ml or 10 micrograms of vancomycin/ml alternating with growth in antibiotic-free medium. Previous in vivo exposure to cloxacillin did not enhance the development of tolerance in vitro. MICs of both cloxacillin and vancomycin did not change significantly during this procedure. Whether the conversion of nontolerant strains to the tolerant state can also occur during antibiotic exposure in treatment of patients remains to be determined.

Surveillance of postoperative infections in thoracic surgery.

Postoperative infections (PIs) are serious complications of thoracic surgery. To gain insight into the nature and the scope of the problem, an 18-month prospective surveillance was conducted at the department of thoracic surgery of the University Hospital Rotterdam, Dijkzigt. PI were classified according to CDC criteria. One hundred and ninety-four out of 983 patients (19.7%) developed one or more PIs and in these 194 patients, 268 PIs were diagnosed. The incidence of PI was 2.0 per 100 days of postoperative stay. The mean postoperative length of stay (LOS) of the 194 patients with PI was 14.1 days longer than those without PI. Deep surgical wound infections (DSWIs) were associated with the longest prolongation of the median postoperative LOS in the hospital (30 days longer). Although lower than DSWIs, incisional surgical wound infections also had a significant prolongation of stay (median 10 days longer). Staphylococcus aureus was the most important pathogen associated with surgical wound infections (SWIs). Phage typing of 29 strains causing SWI showed only two identical pairs, so only a minority of infections could be explained by cross-infection. Older age, and more complicated procedures (e.g. cardiac valve operations) were independent, statistically significant, risk factors for the development of PI. Since there is a progressive trend towards operating on older patients and performing more complicated procedures, the incidence of PI is expected to increase. Therefore it will become increasingly important to develop new strategies to prevent these serious complications.

Efficacy of ciprofloxacin in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis caused by a cloxacillin-tolerant strain and its non-tolerant variant.

The efficacy of ciprofloxacin in treatment and prophylaxis of Staphylococcus aureus endocarditis in rats infected with a strain tolerant to the standard anti-staphylococcal antibiotics cloxacillin, vancomycin and teicoplanin was compared with its non-tolerant variant. After 5 days of treatment with ciprofloxacin 30 mg/kg subcutaneously every 8 h bacterial densities in vegetations from animals infected with the tolerant and the non-tolerant strain were similar. Resistance to ciprofloxacin did not emerge in either strain of S. aureus during treatment. In prophylaxis experiments a single dose of ciprofloxacin (30 mg/kg) administered 30 min before bacterial challenge afforded almost full protection for both the tolerant and the non-tolerant strain. At a lower dose of 6 mg/kg the protective effect was less compared with the higher dose, but no difference in the proportion of sterile vegetations was found between the two strains. Thus tolerance influenced neither treatment nor prophylaxis with ciprofloxacin. For strains of S. aureus tolerant to the usual anti-staphylococcal antibiotics ciprofloxacin could be a useful alternative for the treatment of infections.

Paradoxical dose effect of continuously administered cloxacillin in treatment of tolerant Staphylococcus aureus endocarditis in rats.

The efficacies of different doses of cloxacillin administered by continuous infusion were compared in the treatment of endocarditis in rats caused by a beta-lactam tolerant strain of Staphylococcus aureus and its non-tolerant variant. In-vitro killing of the tolerant strain was maximal at a concentration near the MIC, while at higher concentrations the rate of killing gradually decreased, a paradoxical effect, not found for the non-tolerant strain. During treatment of endocarditis caused by a tolerant strain, the reduction of bacterial numbers in the infected vegetations decreased significantly with increasing doses of cloxacillin. Thus for the tolerant strain a paradoxical dose effect was also apparent in vivo. For the non-tolerant strain this paradoxical effect was not found. Furthermore, continuous administration of cloxacillin was significantly less effective in reducing bacterial numbers in the vegetations for the tolerant strain than for the non-tolerant strain. The results of this study suggest that the phenomenon of tolerance, demonstrated in vitro, may have a significant influence on the outcome of treatment of S. aureus endocarditis with continuously administered cloxacillin, particularly when high doses of antibiotic are used.

Role of tolerance in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis with vancomycin, teicoplanin, and daptomycin.

The role of Staphylococcus aureus tolerance in the treatment and prophylaxis of endocarditis in rats was investigated. The efficacies of vancomycin, teicoplanin, and daptomycin, alone and in combination with rifampin, were compared in rats with endocarditis infected with a tolerant strain of S. aureus and in rats with endocarditis infected with its nontolerant variant. In vitro the cloxacillin-tolerant strain was also tolerant to vancomycin and teicoplanin, but not to daptomycin. However, tolerance to these antibiotics did not influence the results of treatment of experimental S. aureus endocarditis. There was no difference in the bacterial densities in the vegetations of rats infected with either the tolerant or the nontolerant strain after 5 days of treatment with any of the antibiotic regimens. Of all antibiotics, daptomycin was the most effective in reducing bacterial numbers in vegetations. Combination of rifampin with vancomycin or teicoplanin improved the results of treatment for the tolerant as well as the nontolerant strains. Daptomycin was as effective alone as in combination with rifampin. In contrast, tolerance influenced the prophylactic effects of vancomycin and teicoplanin. The proportion of rats with sterile vegetations after prophylaxis with vancomycin or teicoplanin at a low dose was lower for those infected with the tolerant strain than for those infected with the nontolerant strain. A low dose of daptomycin was equally effective against the tolerant and the nontolerant strains. However, higher doses of all three antibiotics afforded almost full protection against both strains.

The effects of medium and rate of freezing on the survival of chlamydias after lyophilization.

The effects of suspension media and rate of freezing on the survival of Chlamydia trachomatis LGV2 and Chlamydia pneumoniae after lyophilization were assessed. The highest loss in infectious elementary bodies (EBs) occurred during lyophilization. The survival was higher after freezing at a rate of 1 degree C min-1 and lyophilization than that after rapid freezing at -70 degrees C or -196 degrees C. The recovery (+/- 5%) was higher when fetal calf serum (FCS) containing glucose, saccharose or lactose were used as lyophilization media than that (0.5-3%) when yolk-sac, skimmed milk or phosphate buffer containing sucrose, glutamine and 10% FCS (SPG) were used. After lyophilization, the survival was not affected in the tested range from 10(4) to 5 x 10(6) inclusion-forming units (ifu) ml-1 prior to freezing. After storage for 4 months at 4 degrees C, the numbers of ifu of both Chlamydia serovars that were recovered were identical to the numbers of ifu immediately after lyophilization. It was concluded that chlamydias can be stored and transported in lyophilized form. However, a loss of 95% in infectious EBs should be taken into account.

Influence of temperature and relative humidity on the survival of Chlamydia pneumoniae in aerosols.

The survival of Chlamydia pneumoniae in aerosols was investigated by using a chamber with a capacity of 114.5 liters. We injected 5 x 10(7) inclusion-forming units (IFU) of C. pneumoniae in aerosols with a droplet size of 3 to 5 microns. Samples were taken after 30 s and every 1 min thereafter. The survival of C. pneumoniae was measured at four temperatures (8.5, 15, 25, and 35 degrees C) and at three different relative humidities (RH) of 5, 50, and 95% for each temperature. The survival rates of Streptococcus pneumoniae, Streptococcus faecalis, Klebsiella pneumoniae, Chlamydia trachomatis LGV2, and cytomegalovirus were also determined at 25 degrees C and 95% RH and compared with that of C. pneumoniae. At the mentioned temperatures and RH, a rapid decrease of C. pneumoniae IFU was observed in the first 30 s. After this the decrease in the number of IFU was more gradual. The survival of C. pneumoniae in aerosols were optimal at 15 to 25 degrees C and 95% RH; it was good compared with those of other microorganisms. A lower death rate was observed only in S. faecalis. In C. trachomatis, the death rate during the first 30 s was higher than that in C. pneumoniae (85 and 53.3%, respectively). After the first 30 s, the death rates in the two organisms were identical. It was concluded that transmission of C. pneumoniae via aerosols was possible. There is probably a direct transmission from person to person, taking into account the relatively short survival period of C. pneumoniae in aerosols.

Endemic acinetobacter in intensive care units: epidemiology and clinical impact.

AIMS: To assess whether Acinetobacter isolates obtained over 20 months in a tertiary care hospital were epidemiologically related; to establish the clinical importance of the organisms; and to identify the isolates according to the recent taxonomy. METHODS: Fifty eight Acinetobacter isolates from 49 patients collected during 1984 and 1985 were investigated. Most isolates were from respiratory tract specimens from intensive care patients. The organisms were typed by cell envelope protein electrophoresis and by a quantitative carbon source growth assay; patients' charts were reviewed to differentiate between colonisation and infection; representative isolates were identified to species level by DNA-DNA hybridisation. RESULTS: Twelve protein profiles were distinguished in the isolates. Forty two isolates were of the same protein profile (profile I); other profiles were observed in a few or single isolates. Cluster analysis of carbon source growth divided profile I isolates into two groups--one of isolates from 1984 and one from 1985. They were identified as A baumannii and associated with infections in eight patients. Four other infections were caused by acinetobacters with other protein profiles (three of A baumannii; one of the unnamed DNA group 3). CONCLUSIONS: Apart from sporadic strains, two strains of the same protein profile, but distinguishable by carbon source growth, were successively endemic. Cluster analysis was a valuable tool in the interpretation of typing and epidemiological data. The 12 (28%) infections of Acinetobacter in 43 patients in intensive care suggest that the presence of these organisms in wards of severely ill patients should be a cause of concern.

Detection of IgG, IgM and IgA antibodies in patients with uncomplicated Chlamydia trachomatis infection: a comparison between enzyme linked immunofluorescent assay and isolation in cell culture.

The diagnostic value of serum IgG, IgM and IgA in patients with uncomplicated urogenital Chlamydia trachomatis infection was compared with isolation in cell culture. C. trachomatis specific antibodies were determined with an enzyme linked immunofluorescent assay using elementary bodies from C. trachomatis serotypes E,F,H,I,J and LGV2 as antigens. At least two sera from each patient were tested and cultures were also established on the same day. Excluding the IgM titres in men, significantly more IgG, IgA and IgM and combinations of these antibodies were observed in culture positive patients. The sensitivity with which IgG titres in men or IgG and/or IgM titres in men and women could be determined, was significantly lower using C. trachomatis LGV2 as the only antigen than when all 6 antigens were used. The presence of 10 or more leucocytes in the urine sediment of men correlated positively with an IgG or an IgG and/or IgM titre.

Epidemiology of bacterial endocarditis in The Netherlands. I. Patient characteristics.

BACKGROUND: Studies of the epidemiology of bacterial endocarditis are usually based on a retrospective review of medical records from referral centers serving diverse patient populations. These studies are therefore likely to suffer from selection bias. We conducted a nationwide prospective epidemiologic study of endocarditis in the Netherlands. METHODS: During a 2-year period, all cases of consecutively hospitalized patients with suspected endocarditis in the Netherlands were reported to us. While hospitalized, patients were visited for an in-person interview and a review of the medical record. RESULTS: Of 559 episodes, 438 met the criteria for endocarditis; these included 89 episodes of prosthetic valve endocarditis and 349 episodes of native valve endocarditis. Adjusted for age- and sex-specific population figures, the incidence was 19 per million person-years. The incidence increased significantly with age, and men were more often affected than women (266 and 172 cases, respectively). Rheumatic and congenital cardiac lesions formed most of the underlying heart diseases. Mitral valve prolapse was present in only 29 patients with native valve endocarditis (8.3%). A history of intravenous drug abuse was present in 32 patients (7.3%). Viridans streptococci, staphylococci, and enterococci together constituted 86% of the isolated bacterial strains. Only 1.1% of the patients had culture-negative endocarditis. Overall case fatality was 19.7% and varied widely according to causative microorganism. CONCLUSION: The distribution of causal microorganisms, the case fatality rate, and the incidence rate of endocarditis are age related. Therefore, a meaningful comparison of data is only possible between population-based cohorts of patients with endocarditis.

Epidemiology of bacterial endocarditis in The Netherlands. II. Antecedent procedures and use of prophylaxis.

BACKGROUND: The reported frequency with which endocarditis is ascribed to an antecedent dental or medical procedure varies from 3% to 62%. METHODS: We performed a nationwide prospective study of the epidemiology of bacterial endocarditis in the Netherlands. During a 2-year period, all consecutively hospitalized patients suspected of having endocarditis were visited while still hospitalized for a review of the medical record and an in-person interview that focused on antecedent procedures and administered prophylaxis. All information was checked with pharmacists and dental and medical practitioners. RESULTS: Of 427 patients with late prosthetic or native valve endocarditis, 275 were eligible for antibiotic prophylaxis because of a previously known cardiac lesion (n = 197) or a prosthetic valve (n = 78). Of these 275 patients, 64 (23.3%) had undergone a procedure with an indication for prophylaxis within 180 days of onset; in 31 (11.3%) the procedures had been within 30 days of onset. Antibiotic prophylaxis had been administered to 17 (26.6%) of the 64 patients and to eight (25.8%) of the 31 patients. CONCLUSION: The results indicate that medical and dental procedures cause only a small fraction of endocarditis. The majority of patients develop the disease along other routes. For an incubation period of 180 days, full compliance with prophylaxis might have prevented endocarditis in 47 (17.1%) of 275 patients with late prosthetic or native valve endocarditis involving a previously known cardiac lesion who underwent a procedure with an indication for prophylaxis. For an incubation period of 30 days, prophylaxis might have prevented endocarditis in 23 (8.4%) of these 275 patients, or 5.3% of all patients with endocarditis (n = 427).

Role of tolerance in cloxacillin prophylaxis of experimental Staphylococcus aureus endocarditis.

The role of tolerance was investigated in the prophylaxis of Staphylococcus aureus endocarditis with cloxacillin in rats. The effect of a single dose of 500 mg/kg, two 80 mg/kg doses 3 h apart, and a single dose of 80 mg/kg, alone or in combination with a single dose of 4 mg of gentamicin/kg, were compared for a tolerant strain of S. aureus and its isogenic nontolerant variant. At all dosages, cloxacillin was significantly less effective in preventing endocarditis with the tolerant strain than with the nontolerant variant. With the high dose of cloxacillin or two successive lower doses, nearly complete protection could be obtained against the nontolerant strain. However, for the tolerant strain, only the combination of cloxacillin and gentamicin afforded almost complete protection. For the tolerant strain, no serum bactericidal activity was found at the time of bacterial challenge after an injection of any dose of cloxacillin. These results suggest that the in vitro phenomenon of tolerance may have relevance in vivo.

Factors influencing the infectivity of Chlamydia pneumoniae elementary bodies on HL cells.

The influence of variations in the pH, NaCl concentration, temperature, and concentrations of calcium and magnesium ions on the survival of Chlamydia pneumoniae elementary bodies (EBs) outside the host cells was investigated. The survival was determined after various incubation periods by counting the inclusion-forming units after C. pneumoniae was cultured for 72 h on monolayers of HL cells. The normal physiological conditions were restored prior to infecting the HL cells with C. pneumoniae. Declines in the infectivities of C. pneumoniae EBs were observed at pH values of lower than 5 and higher than 8 or at NaCl concentrations of less than 80 mM. The viability of C. pneumoniae EBs in SPG medium decreased as the temperature and/or incubation period increased. Incubation temperatures of up to 20 degrees C and incubation periods of up to 48 h did not affect the viability of C. pneumoniae. One hundred percent of the C. pneumoniae EBs were infective after 1 h of incubation at 35 degrees C, whereas 90, 50, and 40% survived after incubations of 8, 24, and 48 h, respectively. The viability of C. pneumoniae was unaffected within the investigated range of Ca2+ and Mg2+ ion concentrations in the medium. The presence of 10% fetal calf serum in the incubation medium had a stabilizing effect on the viability of C. pneumoniae. This effect became more pronounced as the incubation period increased.