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Biomedical subjects

D Pittet

Publications and source records attributed to D Pittet.

At least 91 records · Page 5Linked to original sources

Infection control in Switzerland.

Infection control in hospitals is not mandatory in Switzerland as in the United States. There are more than 300 acute-care hospitals in Switzerland. Hospitals are reimbursed by patient-days rather than diagnosis-related group. However, all five Swiss university hospitals have developed an infection control program. The major criteria for setting up and running these programs are reviewed; data are based on a questionnaire and personal interviewing of each institution. Most of the major criteria exist in all five institutions. Resources allocated to infection control differ markedly. The number of infection control nurses per 250 beds varies between 0.2 and 0.75 for the five hospitals; the activity of those in charge of infection control differs between hospitals. A comparison is made between the Swiss and U.S. programs with regard to some aspects of healthcare and infection control.

Cross Infection↗

Intravascular device-related infections in critically ill patients.

Intravascular device-related infections (IVDRIs) are among the most common nosocomial infections in critically ill patients. Quantitative or semi-quantitative microbiology diagnosis is necessary for their management. Most causative organisms arise from the skin; staphylococci are responsible for two-thirds of the IVDRIs, with Staphylococcus aureus responsible for 5% to 15%. Complications may include septic shock, suppurative thrombophlebitis, and endocarditis. In critically ill patients, intravenous lines are responsible for at least 23% of nosocomial bloodstream infection, which has a mortality of 25% and is associated with a longer stay in intensive care and costs $28,960 per survivor. IVDRIs can be treated with intravenous antibiotics without removing the device, but removal of the catheter is recommended. Prevention is based on careful insertion practice and optimal catheter care. Systemic replacement of the intravenous lines every three to five days is common practice in the USA but not elsewhere in Europe. This issue should be studied, particularly in critically ill patients.

Bacterial Infections↗

Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality.

OBJECTIVE: To determine the excess length of stay, extra costs, and mortality attributable to nosocomial bloodstream infection in critically ill patients. DESIGN: Pairwise-matched (1:1) case-control study. SETTING: Surgical intensive care unit (SICU) in a tertiary health care institution. PATIENTS: All patients admitted in the SICU between July 1, 1988, and June 30, 1990, were eligible. Cases were defined as patients with nosocomial bloodstream infection; controls were selected according to matching variables in a stepwise fashion. METHODS: Matching variables were primary diagnosis for admission, age, sex, length of stay before the day of infection in cases, and total number of discharge diagnoses. Matching was successful for 89% of the cohort; 86 matched case-control pairs were studied. MAIN OUTCOME MEASURES: Crude and attributable mortality, excess length of hospital and SICU stay, and overall costs. RESULTS: Nosocomial bloodstream infection complicated 2.67 per 100 admissions to the SICU during the study period. The crude mortality rates from cases and controls were 50% and 15%, respectively (P < .01); thus, the estimated attributable mortality rate was 35% (95% confidence interval, 25% to 45%). The median length of hospital stay significantly differed between cases and controls (40 vs 26 days, respectively; P < .01). When only matched pairs who survived bloodstream infection were considered (n = 41), cases stayed in the hospital a median of 54 days vs 30 days for controls (P < .01), and cases stayed in the SICU a median of 15 days vs 7 days for controls (P < .01). Thus, extra hospital and SICU length of stay attributable to bloodstream infection was 24 and 8 days, respectively. Extra costs attributable to the infection averaged $40,000 per survivor. CONCLUSIONS: The attributable mortality from nosocomial bloodstream infection is high in critically ill patients. The infection is associated with a doubling of the SICU stay, an excess length of hospital stay of 24 days in survivors, and a significant economic burden.

Case-Control Studies↗

[Nosocomial pneumonia: incidence, morbidity and mortality in the intubated-ventilated patient].

Pneumonia is the leading nosocomial infection in critically ill patients. Its exact frequency is not known because of lack of specificity of the clinical diagnosis and existing standard techniques: ventilator-associated pneumonia (VAP) complicates 7 to 44 (mean 25) per 100 admissions. According to the results of matched case-control studies, VAP is associated with a prolongation of the duration of mechanical ventilation, time in ICU and hospital stay. Estimated extra costs due to VAP average 13,000 SFr per patient (28,000 SFr per survivor). Overall mortality associated with VAP ranges from 40 to 80%, varying with the severity of the underlying illness. Mortality attributable only to the infection accounts for a third of deaths in patients with VAP.

Costs and Cost Analysis↗

Infectious risk factors related to operating rooms.

Risk factors related to operating rooms include patient-associated risks, the operating room environment, ventilation systems, cleansing and sterilization, and operating room personnel. Although constantly debated, surgical wound infection surveillance with appropriate feedback to surgeons is one of the few effective measures that helps reduce surgical infection rates, and we strongly recommend its use. We also recommend the further study of other potential components of effective infection control programs for surgical patients.

Air Microbiology↗

Candida colonization and subsequent infections in critically ill surgical patients.

OBJECTIVE: The authors determined the role of Candida colonization in the development of subsequent infection in critically ill patients. DESIGN: A 6-month prospective cohort study was given to patients admitted to the surgical and neonatal intensive care units in a 1600-bed university medical center. METHODS: Patients having predetermined criteria for significant Candida colonization revealed by routine microbiologic surveillance cultures at different body sites were eligible for the study. Risk factors for Candida infection were recorded. A Candida colonization index was determined daily as the ratio of the number of distinct body sites (dbs) colonized with identical strains over the total number of dbs tested; a mean of 5.3 dbs per patient was obtained. All isolates (n = 322) sequentially recovered were characterized by genotyping using contour-clamped homogeneous electrical field gel electrophoresis that allowed strain delineation among Candida species. RESULTS: Twenty-nine patients met the criteria for inclusion; all were at high risk for Candida infection; 11 patients (38%) developed severe infections (8 candidemia); the remaining 18 patients were heavily colonized, but never required intravenous antifungal therapy. Among the potential risk factors for candida infection, three discriminated the colonized from the infected patients--i.e., length of previous antibiotic therapy (p < 0.02), severity of illness assessed by APACHE II score (p < 0.01), and the intensity of Candida spp colonization (p < 0.01). By logistic regression analysis, the latter two who were the independent factors that predicted subsequent candidal infection. Candida colonization always preceded infection with genotypically identical Candida spp strain. The proposed colonization indexes reached threshold values a mean of 6 days before Candida infection and demonstrated high positive predictive values (66 to 100%). CONCLUSIONS: The intensity of Candida colonization assessed by systematic screening helps predicting subsequent infections with identical strains in critically ill patients. Accurately identifying high-risk patients with Candida colonization offers opportunity for intervention strategies.

Adult↗

Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients.

Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.

Adult↗

Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates.

To further understand how the second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] interacts with its intracellular receptor, we injected 47 highly purified inositol phosphate (InsP) positional isomers in Xenopus oocytes and compared their potency in releasing intracellular Ca2+. The potency of the Ca(2+)-releasing InsPs spanned four orders of magnitude. Seven compounds, including the novel inositol 1,2,4,5-tetrakisphosphate [D/L-Ins (1,2,4,5)P4] and D/L-Ins(1,4,6)P3, had a very high potency. All of these highly active InsPs shared the following structure: two D-trans-equatorial phosphates (eq-P) and one equatorial hydroxyl (eq-OH) attached to ring carbons D-4, D-5, and D-6 (or to the structurally equivalent D-1, D-6, and D-5 carbons). This permissive structure was not sufficient for Ca2+ release, because it was also found in two inactive compounds, Ins(1,6)P2 and Ins(1,3,6)P3. To be active, InsPs also required the structural equivalent of a D-3 eq-OH and/or a D-1 eq-P. Together, our data reveal how the structure of the InsP molecule affects its ability to release Ca2+.

Animals↗

[Computer alert and quality of care: application to the surveillance of hospital infections].

The Centre Informatique of Geneva University Hospital is developing, in the environment of its hospital information system, DIOGENE, a computerized alert system for surveillance of hospital infections. This hospital information system is based on an open distributed architecture and a relational database system, and covers many medical applications. This environment allows the development of alerts useful for detecting patients at risk. The alerts offer to clinicians a mean to control their efficacy in patient care. They are a new application of telematics for surveillance in clinical epidemiology, and are a tool for quality assurance. Two examples of alerts established for hospital infection control activities are presented. The first alert systematically detects all cases of patients colonized by or infected with methicillin-resistant Staphylococcus aureus (MRSA). The second alert helps to organize prospective surveillance of bloodstream infections in order to identify some risk factors for infection and propose preventive measures.

Cost of Illness↗

Importance of pre-existing co-morbidities for prognosis of septicemia in critically ill patients.

OBJECTIVE: To determine admission characteristics associated with the outcome of septicemia in critically ill patients and more specifically assess the prognostic value of pre-existing co-morbidities. DESIGN: 5 year-retrospective cohort study. SETTING: Surgical Intensive Care Unit (ICU-20 beds) in a 1600 bed-tertiary care center. PATIENTS: Among 5457 patients admitted to the ICU between 1984 and 1988, 176 (3.2%) met prospectively-defined criteria for blood culture-proven septicemia (8.77 per 1000 patient-days). Overall septicemic patients had a 5-fold increased risk of death compared to non-septicemic patients (relative risk 5.03, 95% confidence intervals 4.17-6.07, p < 0.0001), and this estimate persisted after stratification according to age, sex, primary diagnosis and conditions of admission to the ICU (emergency/elective). RESULTS: Prognostic factors recorded on admission to ICU that were associated with mortality from septicemia among 173 patients were older age, higher admission Apache II score, gastrointestinal surgery, ultimately and rapidly fatal diseases and the number of co-morbidities in addition to the principal diagnosis (active smoking, alcohol abuse, non-cured malignancy, diabetes mellitus, splenectomy, recent antibiotic therapy, major surgery, or major cardiac event). In the multivariate analysis with logistic regression procedures, Apache II and co-morbidities were identified as the two independent predictors of mortality. CONCLUSIONS: Pre-existing co-morbidities assessed at the admission to the ICU significantly improved the prediction of mortality from septicemia compared to Apache II score alone.

Adult↗

Association of secondary and polymicrobial nosocomial bloodstream infections with higher mortality.

The objective of this study was to characterize microbiological factors independently associated with higher mortality rates following nosocomial bloodstream infection. All patients admitted to the University of Iowa Hospitals and Clinics between 1 July 1989 and 30 June 1990 who developed a nosocomial bloodstream infection were included. The crude in-house mortality for the 364 patients with nosocomial bloodstream infections was 33%. These deaths accounted for 25% of all in-hospital deaths. Significant risk factors for death from bloodstream infection included diagnoses of cancers and diseases of the cardiovascular and respiratory systems (p < 0.01). Neither previous surgery nor neutropenia was associated with higher mortality rates. Whereas the crude mortality rates associated with gram-negative (33%) and gram-positive (31%) bloodstream infections were similar, that associated with fungemia was higher (54%, p < 0.02). The mortality associated with secondary bloodstream infections (46%) was higher than that associated with primary bloodstream infections (28%, p < 0.001). Furthermore, polymicrobial infections had a worse prognosis than infections from which a single pathogen was isolated (p < 0.05). A multivariate, logistic regression model identified four variables that independently predicted mortality (p = 0.025): age (OR 1.01 per year; CI95 1.00-1.02); cancer (OR 2.35, CI95 1.26-4.37) or diseases of the cardiovascular or respiratory systems (OR 2.20, CI95 1.04-4.67); polymicrobial infection (OR 2.34; CI95 1.21-4.53); and secondary bloodstream infection (OR 2.46; CI95 1.50-4.02). The last variable was the strongest independent predictor. Our study demonstrates the importance of microbiological factors in the outcome of nosocomial bloodstream infections.

Age Factors↗

Fibronectin is more active than fibrin or fibrinogen in promoting Staphylococcus aureus adherence to inserted intravascular catheters.

To further define the role of fibrin(ogen) and fibronectin in Staphylococcus aureus adherence to central venous catheters, the amount, chemical integrity, and biologic activity of these proteins adsorbed on lines inserted in hospitalized patients were prospectively studied. Polyurethane cannulas promoted a significantly lower adherence of S. aureus than polyvinyl chloride (P < .01) or Hickman (P < .001) cannulas and contained the lowest amount of immunologically assayed fibronectin but not of fibrin(ogen). Fibrinogen showed an extensive loss of adherence-promoting activity on inserted cannulas, which was related to its proteolytic breakdown, as detected by SDS-PAGE and immunoblots with antifibrinogen antibodies and confirmed by in vitro studies with purified protein fragments. In contrast, either intact or fragmented fibronectin, although present in much lower amounts than fibrin(ogen), could actively promote S. aureus adherence onto intravenous catheters.

Anticoagulants↗

Inositol tetrakisphosphate isomers and elevation of cytosolic Ca2+ in vasopressin-stimulated insulin-secreting RINm5F cells.

Signal generation during the stimulation of insulin secretion by arginine vasopressin (AVP) was investigated in RINm5F cells. AVP (0.1 microM) caused a biphasic cytosolic Ca2+ ([Ca2+]i) rise, namely a rapid transient marked elevation after stimulation followed by a series of oscillations. In the absence of extracellular Ca2+, the sustained oscillations were abolished, while the initial [Ca2+]i transient was only partly decreased, indicating that the former are due to Ca2+ influx and the latter due mainly to mobilization from internal Ca2+ stores. AVP also evoked a transient depolarization of the average membrane potential. AVP-induced Ca2+ influx during the sustained phase, which was strictly dependent on receptor occupancy, was attenuated by membrane hyperpolarization with diazoxide. However, blockade of Ca2+ channels of the L- or T-type was ineffective. AVP stimulated production of diacylglycerol and inositol phosphates; for the latter both [3H] inositol labeling and mass determinations were performed. A transient increase in Ins(1,4,5)P3 was followed by a marked enhancement of Ins(1,3,4,5)P4 (8-fold) peaking at 15 s and gradually returning to basal values. Ins(1,3,4,6)P4 and Ins(3,4,5,6)P4 exhibited the most long-lasting augmentation (4- and 1.7-fold, respectively), and therefore correlated best with the period of sustained [Ca2+]i oscillations. InsP5 and InsP6 were not elevated. The effects of AVP, including the stimulation of insulin secretion from perifused cells, were obliterated by a V1 receptor antagonist. In conclusion, AVP induces protracted [Ca2+]i elevation in RINm5F cells which is associated with long-lasting increases in InsP4 isomers. The accumulation of InsP4 isomers reflects receptor occupancy and accelerated metabolism of the inositol phosphates. Activation of second messenger-operated Ca2+ channels is not necessarily implicated because of the attenuating effect of membrane hyperpolarization.

Arginine Vasopressin↗

InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+ in Xenopus oocytes.

To investigate the role of D-myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] in the regulation of Ca2+ influx, we injected inositol phosphates into Xenopus oocytes and measured Ca(2+)-gated Cl- current to assay intracellular free Ca2+ concentration ([Ca2+]i). To assess Ca2+ influx, we removed extracellular Ca2+ or added the inorganic Ca2+ channel blocker Mn2+ to the extracellular bath and measured the resulting change in Cl- current. Ins(1,3,4,5)P4 did not cause Ca2+ influx when injected alone or when preceded by an injection of Ca2+. In contrast, Ins(1,3,4,5)P4 stimulated Ca2+ influx when injected after the poorly metabolized inositol trisphosphate (InsP3) analogues D-myo-inositol 1,4,5-trisphosphorothioate [Ins(1,4,5)P3S3] or D-myo-inositol 2,4,5-trisphosphate [Ins(2,4,5)P3]. These results indicate that Ins(1,3,4,5)P4 is not sufficient to stimulate Ca2+ influx but acts in synergy with InsP3s to cause Ca2+ influx. We also studied the effect of Ca2+ influx on the immediate metabolism of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in single oocytes. Ca2+ influx shunted the metabolism of Ins(1,4,5)P3 toward the formation of Ins(1,3,4,5)P4 and away from D-myo-inositol 1,4-bisphosphate [Ins(1,4)P2]. These results suggest that there is a positive feedback regulatory mechanism in which Ca2+ influx stimulates Ins(1,3,4,5)P4 production and Ins(1,3,4,5)P4 stimulates further Ca2+ influx.

Animals↗

Contour-clamped homogeneous electric field gel electrophoresis as a powerful epidemiologic tool in yeast infections.

To examine the longitudinal and cross-sectional patterns of yeast colonization in critically ill patients using genotypic characteristics defined by contour-clamped homogeneous electric field (CHEF) gel electrophoresis, 322 clinical isolates of Candida species were prospectively collected from 29 critically ill patients under routine surveillance over a 6-month period. All isolates, recovered from multiple anatomic sites and from the same sites on different days, were characterized by several identification methods (germ tube test), phenotyping (API system), and genotyping (electrophoretic karyotyping). Electrophoretic karyotype (EK) was determined using pulsed field electrophoresis with the CHEF technique. We used a karyotyping system for Candida albicans (EK code) that facilitated intraspecies delineation. C. albicans colonized 83% of the 29 patients. Candida sp. strains isolated from an individual patient had an identical EK pattern, even when isolated from different body sites, and remained the same over a prolonged period, up to 140 days. EK delineated not only the different Candida species, but also different strains of C. albicans. Strains of C. albicans isolated from different patients were distinguished using the EK pattern, but not API system. Minor variations in EK pattern could be demonstrated in a minority of strains recovered from four patients and were interpreted as chromosomal rearrangements between parent strains. Severe candidal infections, including eight episodes of fungemia, occurred in 11 of 29 patients (38%). All patients had been previously colonized with strains with identical EK patterns. Infection occurred a mean of 25 days after initial surveillance cultures grew yeast. No horizontal transmission could be demonstrated during the study period. In conclusion, EK is a reproducible, stable marker allowing inter-, as well as, intraspecies Candida strain delineation. EK strain delineation is a useful tool in candidal epidemiologic and pathogenic studies. Yeast colonization with the same strain preceded infection in critically ill patients.

Adolescent↗