Evaluating and predicting the ecologic impact of antibiotics.
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Animals↗
Biomedical subjects
C Brun-Buisson
Publications and source records attributed to C Brun-Buisson.
Outcomes of primary and catheter-related bacteremia. A cohort and case-control study in critically ill patients.
We studied a cohort of 2201 patients hospitalized in 15 French intensive care units (ICUs) for > or = 48 h during a 4-mo period to assess the incidence and outcomes of primary and definite catheter-related bloodstream (CRB) or secondary nosocomial bloodstream infection (NBSI). Variables associated with ICU death and duration of stay were determined by logistic regression, and attributable mortality and length of stay (LOS) from a nested matched case-control (96 pairs) study, stratified on the source of bacteremia. Bacteremia occurred in 5% (95% CI 4.1-6%) of patients with > or = 48 h ICU stay. Primary, CRB, and secondary NBSI accounted for 29%, 26%, and 45% of the 111 episodes, respectively. NBSI was associated with a markedly increased risk of death (OR = 4.6; 95% CI 2.9-7.1) and an attributable mortality of 35% (95% CI, 28%-47%). In the case-control study, the excess mortality was 20% (p = 0.03) in patients with primary bacteremia and CRB, and 55% (p < 0.001) for secondary bacteremia; in patients with CRB only, the excess mortality was 11.5%. The median excess ICU LOS in survivors of NBSI was 9.5 d, and was similar, irrespective of its source. The risk of mortality associated with primary and catheter-related bacteremia appears much lower than that of secondary bacteremia, but is sizable, and the excess LOS incurred by the various categories of bacteremia is comparable. Differentiating catheter-related bacteremia from both primary and other secondary bacteremia appears warranted in studies conducted in critically ill patients.
Bacteremia↗
[The therapeutic approach to necrotizing fasciitis].
Necrotizing fasciitis are characterized by the necrosis of fascias, and their severe consequences in terms of morbidity and mortality. An early diagnosis, based on sometimes subtle cutaneous lesions (associated to a sepsis syndrome) allows to start resuscitation and decide on a probable surgery. 3 major forms can be distinguished: streptococcal fasciitis, due to beta-hemolytic streptococci, often following minor trauma, and increasingly associated to a streptococcal toxic shock syndrome (STTS); clostridial gangrene (often polymicrobial when developed on a open wound or after surgery); and synergistic gangrene due to a mixed aerobic-anaerobic flora. Other apparently "primitive" necrotizing fasciitis, caused by specific organisms, may occur in debilitated patients. The prognosis depends on age, comorbidity, and above all on the severity of the sepsis syndrome. Initial resuscitation involves controlling the hypotension and organ dysfunction associated with severe sepsis, and is usually dominated by a severe hypovolemia. Penicillin G remains the key antibiotic for streptococcal and clostridial fasciitis, with a broad spectrum including enterobacteriaceae, streptococci and enterococci, and anaerobes (including Bacteroides spp.) in other types or when the etiology is unknown. In patients presenting with STSS, a combination of clindamycin (or rifampin) to penicillin is recommended, because of their effect on exotoxin production; administration of non-specific immunoglobulins also appears to improve the outcome of patients affected. Hyperbaric oxygen therapy has not proved effective. Early surgical debridement largely influences the prognosis. The prevention of complications associated with long-term intensive care, including early nutritional support and prevention of a thromboembolic disease, is also important.
Fasciitis, Necrotizing↗
Association of noninvasive ventilation with nosocomial infections and survival in critically ill patients.
CONTEXT: Invasive life-support techniques are a major risk factor for nosocomial infection. Noninvasive ventilation (NIV) can be used to avoid endotracheal intubation and may reduce morbidity among patients in intensive care units (ICUs). OBJECTIVE: To determine whether the use of NIV is associated with decreased risk of nosocomial infections and improved survival in everyday clinical practice among patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) or hypercapnic cardiogenic pulmonary edema (CPE). DESIGN AND SETTING: Matched case-control study conducted in the medical ICU of a French university hospital from January 1996 through March 1998. PATIENTS: Fifty patients with acute exacerbation of COPD or severe CPE who were treated with NIV for at least 2 hours and 50 patients treated with mechanical ventilation between 1993 and 1998 (controls), matched on diagnosis, Simplified Acute Physiology Score II, Logistic Organ Dysfunction score, age, and no contraindication to NIV. MAIN OUTCOME MEASURES: Rates of nosocomial infections, antibiotic use, lengths of ventilatory support and of ICU stay, ICU mortality, compared between cases and controls. RESULTS: Rates of nosocomial infections and of nosocomial pneumonia were significantly lower in patients who received NIV than those treated with mechanical ventilation (18% vs 60% and 8% vs 22%; P<.001 and P =.04, respectively). Similarly, the daily risk of acquiring an infection (19 vs 39 episodes per 1000 patient-days; P =.05), proportion of patients receiving antibiotics for nosocomial infection (8% vs 26%; P =.01), mean (SD) duration of ventilation (6 [6] vs 10 [12] days; P =.01), mean (SD) length of ICU stay (9 [7] vs 15 [14] days; P =.02), and crude mortality (4% vs 26%; P =.002) were all lower among patients who received NIV than those treated with mechanical ventilation. CONCLUSIONS: Use of NIV instead of mechanical ventilation is associated with a lower risk of nosocomial infections, less antibiotic use, shorter length of ICU stay, and lower mortality. JAMA. 2000;284:2361-2367.
APACHE↗
Introduction--infection and critical illness: genetic and environmental aspects of susceptibility and resistance.
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Critical Illness↗
Poisoning with foxglove extract: favorable evolution without Fab fragments.
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Adult↗
The epidemiology of the systemic inflammatory response.
OBJECTIVE: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection. DESIGN: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients. RESULTS: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and >50% of all ICU patients; in surgical ICU patients, SIRS occurs in >80% patients. Trauma patients are at particularly high risk of SIRS, and most these patients do not have infection documented. The prevalence of infection and bacteraemia increases with the number of SIRS criteria met, and with increasing severity of the septic syndromes. About one-third of patients with SIRS have or evolve to sepsis. Sepsis may occur in approximately 25% of ICU patients, and bacteraemic sepsis in 10%. In such patients, sepsis evolves to severe sepsis in >50% of cases, whereas evolution to severe sepsis in non-ICU patients is about 25%. Severe sepsis and septic shock occur in 2%-3% of ward patients and 10%-15% or more ICU patients, depending on the case-mix; 25% of patients with severe sepsis have shock. There is a graded severity from SIRS to sepsis, severe sepsis and septic shock, with an associated 28-d mortality of approximately 10%, 20%, 20%-40%, and 40%-60%, respectively. Mortality rates are similar within each stage, whether infection is documented or not, and microbiological characteristics of infection do not substantially influence outcome, although the source of infection does. While about three of four deaths occur during the first months after sepsis, the septic syndromes significantly impact on long-term outcome, with an estimated 50% reduction of life expectancy over the following five years. The major determinants of outcome, both short-term and long-term, of patients with sepsis are the severity of underlying diseases and comorbidities, the presence of shock and organ failures at onset of sepsis or evolving thereafter. It has been estimated that two-thirds of the overall mortality can be attributed to sepsis. CONCLUSIONS: The prevalence of sepsis in ICU patients is very high, and most patients have clinically or microbiologically documented infection, except in specific subset of patients. The prognosis of septic syndromes is related to underlying diseases and the severity of the inflammatory response and its sequelae, reflected in shock and organ dysfunction/failures.
Cohort Studies↗
New tools in diagnosing catheter-related infections.
Clinical criteria alone are insufficient to allow a diagnosis of intravascular catheter-related sepsis (CRS). A definite diagnosis of CRS usually requires removal of the catheter for quantitative catheter tip culture. However, only about 15-25% of central venous catheters (CVC) removed because infection is suspected actually prove to be infected, and the diagnosis is always retrospective. Other diagnostic tests, such as differential quantitative blood cultures from samples taken simultaneously from the catheter and a peripheral vein, have been proposed to avoid unjustified removal of the catheter and the potential risks associated with the placement of a new catheter at a new site: a central-to-peripheral blood culture colony count ratio of 5:1 to 10:1 is considered indicative of CRS. Despite its high specificity, the latter diagnostic technique is not routinely used in clinical practice because of its complexity and cost. The measurement of the differential time to positivity between hub blood (taken from the catheter port) and peripheral blood cultures might be a reliable tool facilitating the diagnosis of CRS in situ. In an in vitro study, we found a strong relationship between the inoculum size of various microorganisms and the time to positivity of cultures. When the times to positivity of cultures of blood taken simultaneously from central and peripheral veins in patients with and without CRS were examined, we found that earlier positivity of central vs peripheral vein blood cultures was highly correlated with CRS. Using a cut-off value of +120 min, the "differential time to positivity" of the paired blood samples, defined as time to positivity of the peripheral blood minus that of the hub blood culture, had 91% specificity and 94% sensitivity for the diagnosis of CRS. This method may be coupled with other techniques that have high negative predictive value, such as skin cultures at the catheter exit site. This diagnostic test can be proposed for routine clinical practice in most hospitals using automatic devices for blood cultures positivity detection. Endoluminal brushing of the catheter is considered sensitive and specific for the diagnosis of CRS, but the risk of embolisation or subsequent bacteraemia should be considered. Gram staining and the acridine-orange leucocyte cytospin test on through-catheter blood culture have been proposed for rapid diagnosis of CRS without catheter removal. The technique, which requires 100 microl catheter blood and the use of light and ultraviolet microscopy, is considered simple, rapid (30 min) and inexpensive. In conclusion, diagnostic tools such as paired blood cultures or Gram staining and the acridine-orange leucocyte cytospin test should allow a diagnosis of CRS without catheter removal in cancer patients.
Algorithms↗
Comparison of systematic versus selective screening for methicillin-resistant Staphylococcus aureus carriage in a high-risk dermatology ward.
OBJECTIVE: To compare two strategies for screening methicillin-resistant Staphylococcus aureus (MRSA) carriers in a high-risk dermatology ward: systematic screening of all admitted patients versus selective screening of patients at risk. DESIGN: The two strategies were applied prospectively during two consecutive periods. In period A (8.5 months), only patients transferred from other wards, or with a history of prior hospitalization, or presenting chronic wounds or disease with denuded skin were considered at high risk of MRSA carriage and sampled. In period B (7.5 months), all admitted patients were systematically screened. End-points were the number of patients having a MRSA-positive screening sample on admission during period B and having none of the risk factors used in period A, the rate of imported MRSA cases, and the rate of acquired cases. SETTING: A 1,032-bed university hospital with a 19-bed inpatient dermatology ward, a referral center for toxic epidermal necrolysis and severe extensive dermatoses. PATIENTS: The study included 729 dermatology inpatients (370 in period A and 359 in period B). RESULTS: During period A, screening samples were obtained on admission for 30% of patients (77% of the patients at risk) and identified 25 MRSA carriers. During period B, 90.5% of admitted patients were screened, and 26 MRSA carriers were detected on admission; all of these patients belonged to at least one predefined category at risk for carriage. Overall rates of imported and acquired cases were similar between the two periods (6.8% vs 7.5%, and 2.9% vs 2.4%, respectively). CONCLUSIONS: A screening strategy targeted to patients at risk of harboring MRSA has similar sensitivity and is more cost-effective than a strategy of systematic screening to identify MRSA carriers on admission.
Cross Infection↗
Appropriate use of restricted antimicrobial agents in hospitals: the importance of empirical therapy and assisted re-evaluation.
We evaluated the appropriateness of use of restricted antimicrobial agents in the context of a newly implemented order form and delivery system for restricted antimicrobial agents, using sequential prospective audits of prescriptions. Four antimicrobial agents were selected: glycopeptides (61 prescriptions), ciprofloxacin (42), piperacillin-tazobactam (42) and imipenem- cilastatin (47). The justification and adequacy of the antibiotic or combination used, reassessment of therapy and duration of treatment were appraised with reference to the clinical situation and hospital's guidelines. Of the 192 prescriptions, 30 (16%) were empirical therapy, 95 (49%) empirical and secondarily documented and 67 (35%) initially documented therapy. Overall, 73% of prescriptions conformed to guidelines, but the adequacy varied from 93% for vancomycin to only 38% for ciprofloxacin. Of 83/157 initially inadequate prescriptions, 42 (51%) were switched according to guidelines, but only 14% of ciprofloxacin prescriptions were adapted later. An intervention audit with counselling on ciprofloxacin usage increased this rate to 75%. Although implementation of the guidelines resulted in a marked reduction in overall antimicrobial costs, inappropriate antibiotic usage may persist for some drugs despite restricted access. These results emphasize the need for combined interventions using education and expert counselling, targeted to classes of antibiotic for which inappropriate usage is most common.
Anti-Bacterial Agents↗
Are institutional review boards effective in safeguarding patients in intensive care units?
Institutional Review Boards have been recently audited in the US, and a great deal of concerns and criticisms appeared in the medical literature and the lay press. Globally, these comments questioned the efficiency of Institutional Review Boards in fulfilling their basic mission, the protection of patients subjected to biomedical research. Vulnerable populations, such as psychiatric and incompetent patients, were particularly identified. In intensive care units, conducting research in critically ill patients unable to give informed consent themselves remains a hot issue. Several possibilities have been proposed and assessed in the recent past: pre-emptive (global) consent, proxy consent from a surrogate, deferred consent, and, more recently, waiver of consent for emergency research. Obviously, the inability to deal with this major obstacle (i.e. obtaining consent from incompetent patients) would lead to the cessation of any research in intensive care units, which is hardly acceptable and certainly unethical. Recent published studies have reported over-mortality in treatment groups, posing new questions: who should be informed of those failures, and when? What is the role of Institutional Review Boards in preventing such an issue? What type of indemnity should be proposed to the family of deceased patients during a trial?
Journal Article↗
Hemodynamic tolerance of intermittent hemodialysis in critically ill patients: usefulness of practice guidelines.
Poor hemodynamic tolerance of intermittent hemodialysis (IHD) is a common problem for patients in an intensive care unit (ICU). New dialysis strategies have been adapted to chronic hemodialysis patients with cardiovascular insufficiency. To improve hemodynamic tolerance of IHD, specific guidelines were progressively implemented into practice through the year 1996 in our 26-bed medical ICU. To evaluate the efficiency of these guidelines we retrospectively compared all IHD performed during the years before (1995) and after (1997) implementation of these recommendations. Forty-five patients underwent 248 IHD sessions in 1995 and 76 patients underwent 289 IHD sessions in 1997. The two populations were similar for age, sex, chronic hemodialysis (26% versus 17%), and secondary acute renal failure. In 1997, patients were more severely ill with a higher SAPS II (50 +/- 17 versus 59 +/- 24; p = 0.036), and more patients required epinephrine or norepinephrine infusion before dialysis sessions (16% versus 34%; p < 0.0001). The compliance to guidelines was high, inducing a significant change in IHD modalities. As a result, hemodynamic tolerance was significantly better in 1997, with less systolic blood pressure drop at onset (33% versus 21%, p = 0. 002) and during the sessions (68% versus 56%, p = 0.002). IHD with hypotensive episode or need for therapeutic interventions were less frequent in 1997 (71% versus 61%, p = 0.015). The ICU mortality was similar (53.3% in 1995 versus 47.3% in 1997; p = 0.52) but death rate in 1997, but not in 1995, was significantly less than predicted from SAPS II (47.3% versus 65.6%; p = 0.02). Length of ICU stay was also reduced for survivors in 1997 (p = 0.04). Implementation of practice guidelines for intermittent hemodialysis in ICU patients lessens hemodynamic instability and may improve outcome.
Critical Illness↗
[Treatment of antibiotic-resistant bacteria at the intensive care unit: a therapy dilemma].
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Bacterial Infections↗
Predictors of mortality in acute respiratory distress syndrome. Focus On the role of right heart catheterization.
Right heart catheterization (RHC) has been suspected of increasing mortality. The acute respiratory distress syndrome (ARDS) is a frequent reason for RHC. We designed a retrospective cohort study of 119 consecutive ARDS patients admitted to two medical intensive care units of tertiary care hospitals in which two different approaches are used for hemodynamic monitoring: RHC on demand (Henri Mondor Hospital [HM]) and no use of RHC (Ambroise Paré Hospital [AP]). The study tried to identify risk factors for death, and to assess the influence of RHC, with adjustment for the intensity of hemodynamic support as a confounding factor, using 98 patients in whom the delay between onset of ARDS, use of vasopressors, and RHC did not exceed 48 h. Several variables, including septic shock, cause of ARDS, Simplified Acute Physiology Score (SAPS) II, use of epinephrine/norepinephrine, and presence of RHC were entered into a logistic regression model to evaluate their independent prognostic roles. Mortality was different at HM and AP (36 of 55 patients [65.5%] versus 16 of 43 patients [37.2%], p < 0.005), and 29 of the 35 RHC-monitored patients died (82.8%), as compared with 23 of 63 patients (36.5%) treated without RHC (p < 0.0001). However, administration of epinephrine/norepinephrine and a nonpulmonary cause of ARDS were each independently associated with death. It is only when administration of vasopressors was omitted from the model that RHC, septic shock, and SAPS II became independent predictors of mortality. These results suggest that: (1) the use of vasopressors, but not of RHC, represents an important prognostic factor; and (2) not taking into account the use of these drugs may be misleading when assessing the influence of RHC on outcome.
Adult↗
[NSAID-induced necrotizing fascitis]
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Journal Article↗
[NSAID-induced necrotizing fasciitis].
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Anti-Inflammatory Agents, Non-Steroidal↗
Control of endemic methicillin-resistant Staphylococcus aureus: a cost-benefit analysis in an intensive care unit.
CONTEXT: Despite the success of some countries in controlling endemic methicillin-resistant Staphylococcus aureus (MRSA), such programs have not been implemented for some hospitals with endemic infection because of concerns that these programs would be costly and of limited benefit. OBJECTIVE: To compare the costs and benefits of an MRSA control program in an endemic setting. DESIGN AND SETTING: Case-control study conducted at a medical intensive care unit (ICU) of a French university hospital with a 4% prevalence of MRSA carriage at ICU admission. PATIENTS: Twenty-seven randomly selected patients who had ICU-acquired MRSA infection between January 1993 and June 1997, matched to 27 controls hospitalized during the same period without MRSA infection. MAIN OUTCOME MEASURES: Intensive care unit costs attributable to MRSA infection, computed from excess therapeutic intensity in cases using estimates from a cost model derived in the same ICU, were compared with costs of the control program, derived from time-motion study of nurses and physicians. The threshold for MRSA carriage that would make the control strategy dominant was determined; sensitivity analyses varied rates of MRSA transmission and ratio of infection to transmission, length of ICU stay, and costs of isolation precautions. RESULTS: The mean cost attributable to MRSA infection was US $9275 (median, $5885; interquartile range, $1400-$16,720). Total costs of the control program ranged from $340 to $1480 per patient. A 14% reduction in MRSA infection rate resulted in the control program being beneficial. In sensitivity analyses, the control strategy was dominant for a prevalence of MRSA carriage on ICU admission ranging from 1% to 7%, depending on costs of control measures and MRSA transmission, for infection rates greater than 50% following transmission. CONCLUSIONS: In this example of a hospital with endemic MRSA infection, selective screening and isolation of carriers on ICU admission are beneficial compared with no isolation.
Adult↗
Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures.
BACKGROUND: A method of diagnosing catheter-related infection (CRI) without removing the catheter would be useful. An earlier positivity of central compared with peripheral venous-blood cultures may be associated with catheter-related bacteraemia. We evaluated prospectively the differential time to positivity (DTP) of paired blood cultures drawn simultaneously via the catheter hub and from a peripheral venous site. METHODS: Over a 14-month period in an intensive-care unit of a cancer referral centre, simultaneous hub-blood and peripheral-blood cultures (a mean of two per patient) were obtained from patients with a suspected CRI. According to clinical criteria and quantitative culture of the catheter tip, cases were classified as CRI or sepsis of other origin. At least one pair of hub-blood and peripheral-blood cultures was obtained within 48 h before catheter removal, and we recorded the DTP between hub-blood and peripheral-blood cultures with an automatic device for detection of blood culture positivity. FINDINGS: We analysed 93 catheters removed because of suspicion of CRI. In 28 episodes, the same micro-organisms were found in both hub-blood and peripheral-blood cultures. A diagnosis of definite bacteraemic CRI was made in 16 of the 17 patients in whom a positive hub-blood culture was detected at least 2 hours earlier than peripheral-blood culture. About half (9/17) of these episodes occurred in long-term (>30 days) devices. CRI was excluded in ten of the 11 patients with a DTP lower than 2 h. The DTP of paired blood cultures was significantly greater in patients with CRI than in others (p<10(-4)). A cut-off DTP value of 120 min had 91% specificity and 94% sensitivity for the diagnosis of CRI. Three of 17 episodes with only hub-blood culture positive were associated with CRI. INTERPRETATION: This prospective study suggests that measurement of the differential time to positivity between hub-blood and peripheral-blood cultures is a simple and reliable tool for in-situ diagnosis of catheter-related sepsis in cancer patients. Further studies are needed to confirm these data for short-term catheters.
Bacteremia↗