Serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: a preliminary report.

BACKGROUND: The usefulness of procalcitonin (PCT) measurement in critically ill medical patients with suspected nosocomial infection is unclear. The aim of the study was to assess PCT value for the early diagnosis of bacterial nosocomial infection in selected critically ill patients. METHODS: An observational cohort study in a 15-bed intensive care unit was performed. Seventy patients with either proven (n = 47) or clinically suspected but not confirmed (n = 23) nosocomial infection were included. Procalcitonin measurements were obtained the day when the infection was suspected (D0) and at least one time within the 3 previous days (D-3 to D0). Patients with proven infection were compared to those without. The diagnostic value of PCT on D0 was determined through the construction of the corresponding receiver operating characteristic (ROC) curve. In addition, the predictive value of PCT variations preceding the clinical suspicion of infection was assessed. RESULTS: PCT on D0 was the best predictor of proven infection in this population of ICU patients with a clinical suspicion of infection (AUROCC = 0.80; 95% CI, 0.68-0.91). Thus, a cut-off value of 0.44 ng/mL provides sensitivity and specificity of 65.2% and 83.0%, respectively. Procalcitonin variation between D-1 and D0 was calculated in 45 patients and was also found to be predictive of nosocomial infection (AUROCC = 0.89; 95% CI, 0.79-0.98) with a 100% positive predictive value if the +0.26 ng/mL threshold value was applied. Comparable results were obtained when PCT variation between D-2 and D0, or D-3 and D0 were considered. In contrast, CRP elevation, leukocyte count and fever had a poor predictive value in our population. CONCLUSION: PCT monitoring could be helpful in the early diagnosis of nosocomial infection in the ICU. Both absolute values and variations should be considered and evaluated in further studies.

Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome.

INTRODUCTION: Management of the early stage of sepsis is a critical issue. As part of it, infection control including appropriate antibiotic therapy administration should be prompt. However, microbiological findings, if any, are generally obtained late during the course of the disease. The potential interest of procalcitonin (PCT) as a way to assess the clinical efficacy of the empirical antibiotic therapy was addressed in the present study. METHODS: An observational cohort study including 180 patients with documented sepsis was conducted in our 15-bed medical intensive care unit (ICU). Procalcitonin measurement was obtained daily over a 4-day period following the onset of sepsis (day 1 (D1) to D4). The PCT time course was analyzed according to the appropriateness of the first-line empirical antibiotic therapy as well as according to the patient outcome. RESULTS: Appropriate first-line empirical antibiotic therapy (n = 135) was associated with a significantly greater decrease in PCT between D2 and D3 (DeltaPCT D2-D3) (-3.9 (35.9) vs. +5.0 (29.7), respectively; P < 0.01). In addition, DeltaPCT D2-D3 was found to be an independent predictor of first-line empirical antibiotic therapy appropriateness. In addition, a trend toward a greater rise in PCT between D1 and D2 was observed in patients with inappropriate antibiotics as compared with those with appropriate therapy (+5.2 (47.4) and +1.7 (35.0), respectively; P = 0.20). The D1 PCT level failed to predict outcome, but higher levels were measured in the nonsurvivors (n = 51) when compared with the survivors (n = 121) as early as D3 (40.8 (85.7) and 21.3 (41.0), respectively; P = 0.04). Moreover, PCT kinetics between D2 and D3 were also found to be significantly different, since a decrease >or= 30% was expected in the survivors (log-rank test, P = 0.04), and was found to be an independent predictor of survival (odds ratio = 2.94; 95% confidence interval 1.22 to 7.09; P = 0.02). CONCLUSIONS: In our study in an ICU, appropriateness of the empirical antibiotic therapy and the overall survival were associated with a greater decline in PCT between D2 and D3. Further studies are needed to assess the utility of the daily monitoring of PCT in addition to clinical evaluation during the early management of sepsis.

Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients.

BACKGROUND: Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT. METHODS: review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1st September, 2006 and 31st July, 2007. RESULTS: 179 episodes of either primary (n = 117) or secondary (n = 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; p < 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16-0.70; p = 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (n = 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699-0.879, vs. 0.934, 95% CI: 0.881-0.970, respectively; p < 0.050). CONCLUSION: In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.

Performance of N-terminal-pro-B-type natriuretic peptide in critically ill patients: a prospective observational cohort study.

INTRODUCTION: The purpose of this study was to assess the accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) as a diagnostic tool to recognize acute respiratory failure of cardiac origin in an unselected cohort of critically ill patients. METHODS: We conducted a prospective observational study of medical ICU patients. NT-proBNP was measured at ICU admission, and diagnosis of cardiac dysfunction relied on the patient's clinical presentation and echocardiography. RESULTS: Of the 198 patients included in this study, 102 (51.5%) had evidence of cardiac dysfunction. Median NT-proBNP concentrations were 5,720 ng/L (1,430 to 15,698) and 854 ng/L (190 to 3,560) in patients with and without cardiac dysfunction, respectively (P < 0.0001). In addition, NT-proBNP concentrations were correlated with age (rho = 0.43, P < 0.0001) and inversely correlated with creatinine clearance (rho = -0.58, P < 0.0001). When evaluating the performance of NT-proBNP concentrations to detect cardiac dysfunction, the area under the receiver operating characteristic (ROC) curve was 0.76 (95% confidence interval (CI) 0.69 to 0.83). In addition, a stepwise logistic regression model revealed that NT-proBNP (odds ratio (OR) = 1.01 per 100 ng/L, 95% CI 1.002 to 1.02), electrocardiogram modifications (OR = 11.03, 95% CI 5.19 to 23.41), and severity assessed by organ system failure score (OR = 1.63 per point, 95% CI 1.17 to 2.41) adequately predicted cardiac dysfunction. The area under the ROC curve of this model was 0.83 (95% CI 0.77 to 0.90). CONCLUSIONS: NT-proBNP measured at ICU admission might represent a useful marker to exclude cardiac dysfunction in critically ill patients.

Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either Gram negative or Gram positive bacteria.

BACKGROUND: In the ICU, bacteremia is a life-threatening infection whose prognosis is highly dependent on early recognition and treatment with appropriate antibiotics. Procalcitonin levels have been shown to distinguish between bacteremia and noninfectious inflammatory states accurately and quickly in critically ill patients. However, we still do not know to what extent the magnitude of PCT elevation at the onset of bacteremia varies according to the Gram stain result. METHODS: Review of the medical records of every patient treated between May, 2004 and December, 2006 who had bacteremia caused by either Gram positive (GP) or Gram negative (GN) bacteria, and whose PCT dosage at the onset of infection was available. RESULTS: 97 episodes of either GN bacteremia (n = 52) or GP bacteremia (n = 45) were included. Procalcitonin levels were found to be markedly higher in patients with GN bacteremia than in those with GP bacteremia, whereas the SOFA score value in the two groups was similar. Moreover, in the study population, a high PCT value was found to be independently associated with GN bacteremia. A PCT level of 16.0 ng/mL yielded an 83.0% positive predictive value and a 74.0% negative predictive value for GN-related bacteremia in the study cohort (AUROCC = 0.79; 95% CI, 0.71-0.88). CONCLUSION: In a critically ill patient with clinical sepsis, GN bacteremia could be associated with higher PCT values than those found in GP bacteremia, regardless of the severity of the disease.

Plasma antioxidant status in septic critically ill patients: a decrease over time.

Severe septic states in humans are responsible for intense intravascular oxidative stress, which induces numerous adaptive mechanisms. We determined time sequence changes in total plasma antioxidant capacity (TAC) and major plasma antioxidant concentrations, which have not been fully explained in septic conditions. A cohort of 56 consecutive septic patients (septic shock n = 37, severe sepsis n = 19) and six healthy volunteers. We compared TAC and antioxidant levels in patients with one of two degrees of septic states, at the onset of illness, to those of healthy volunteers. Thereafter, over a 10-day follow-up, we observed daily the time sequence changes of the two septic populations in terms of TAC and antioxidants. At the onset, there was no difference between the three groups in terms of TAC values (healthy subjects 2.18 +/- 0.04; severe sepsis 2.03 +/- 0.07; septic shock 2.09 +/- 0.09), then an equivalent time decline was observed in the two septic populations whatever the severity. TAC was statistically linked to uric acid, proteins in particular albumin and bilirubin (multivariate analysis), but no correlation was found with any vitamin (A, C and E). A sharp and persistent decrease in vitamin C concentrations was underlined. TAC, unaffected at first, deteriorated over time whatever the severity of the infection in these critically ill patients. TAC, unable to distinguish severe sepsis and septic shock, is unlikely to be a particularly useful outcome measure.

Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia.

OBJECTIVE: To determine whether the use of a nurse-implemented sedation protocol could reduce the incidence of ventilator-associated pneumonia in critically ill patients. DESIGN: Two-phase (before-after), prospective, controlled study. SETTING: University-affiliated, 11-bed medical intensive care unit. PATIENTS: Patients requiring mechanical ventilation for >or=48 hrs and sedative infusion with midazolam or propofol alone. INTERVENTIONS: During the control phase, sedatives were adjusted according to the physician's decision. During the protocol phase, sedatives were adjusted according to a protocol developed by a multidisciplinary team including nurses and physicians. The protocol was based on the Cambridge scale, and sedation level was adjusted every 3 hrs by the nurses. Standard practices, including weaning from the ventilator and diagnosis of VAP, were the same during both study phases. MEASUREMENTS AND MAIN RESULTS: A total of 423 patients were enrolled (control group, n = 226; protocol group, n = 197). The incidence of VAP was significantly lower in the protocol group compared with the control group (6% and 15%, respectively, p = .005). By univariate analysis (log-rank test), only use of a nurse-implemented protocol was significantly associated with a decrease of incidence of VAP (p < .01). A nurse-implemented protocol was found to be independently associated with a lower incidence of VAP after adjustment on Simplified Acute Physiology Score II in the multivariate Cox proportional hazards model (hazard rate, 0.81; 95% confidence interval, 0.62-0.95; p = .03). The median duration of mechanical ventilation was significantly shorter in the protocol group (4.2 days; interquartile range, 2.1-9.5) compared with the control group (8 days; interquartile range, 2.2-22.0; p = .001), representing a 52% relative reduction. Extubation failure was more frequently observed in the control group compared with the protocol group (13% and 6%, respectively, p = .01). There was no significant difference in in-hospital mortality (38% vs. 45% in the protocol vs. control group, respectively, p = .22). CONCLUSIONS: In patients receiving mechanical ventilation and requiring sedative infusions with midazolam or propofol, the use of a nurse-implemented sedation protocol decreases the rate of VAP and the duration of mechanical ventilation.

Serum procalcitonin measurement contribution to the early diagnosis of candidemia in critically ill patients.

BACKGROUND: Candidemia is a life-threatening infection in the ICU whose prognosis is highly dependent on the stage at which it is recognized. Procalcitonin (PCT) levels have been shown to accurately distinguish between bacteremia and noninfectious inflammatory states in critically ill patients with clinical signs of sepsis. Little is known about the accuracy of PCT for the diagnosis of candidemia in this setting. SETTING: A medical intensive care unit in a teaching hospital. PATIENTS AND METHODS: Review of the medical records of every non-neutropenic patient with either bacteremia or candidemia and clinical sepsis in whom PCT dosage at the onset of infection was available between May 2004 and December 2005. RESULTS: Fifty episodes of either bacteremia (n=35) or candidemia (n=15) were included. PCT levels were found to be markedly higher in patients with bacteremia than in those with candidemia. Moreover, a low PCT value was found to be an independent predictor of candidemia in the study population. According to the calculation of the area under the receiver operating characteristic curve, PCT was found to be accurate in distinguishing between candidemia and bacteremia (0.96 [0.03]). A PCT level of higher than 5.5 ng/ml yields a 100% negative predictive value and a 65.2% positive predictive value for candidemia-related sepsis. CONCLUSION: A high PCT value in a critically ill non-neutropenic patient with clinical sepsis is unlikely in the setting of candidemia.

[Providing medical files to patients: analysis of 52 requests]. / Communication du dossier médical aux patients: analyse de 52 demandes.

BACKGROUND: Since enactment of a statute on 4 March 2002 to allow patients direct access to their medical files, the number of requests for these files has increased substantially. The objective of this survey was to learn the patients' motivations for requesting files, what they did with them once they received them, and the effects of this direct access on the patient and on the relationship and confidentiality between physician and patient. METHODS: A questionnaire was sent to 100 persons randomly selected among patients requesting their medical file from the Dijon University Hospital Center after the new law became effective. RESULTS: The response rate to this survey was 58%. In 75% of the cases, patients requested their own medical files. Their reasons varied: curiosity (38%), transfer of the file to another physician (35%), disagreement with the medical team (12%), death of a family member (10%). After receiving the file, 35% of the respondents read it with a physician and 13% with their attorney. In two thirds of the cases, the medical files were transmitted directly to a third party: physician (51%), attorney (34%), or insurance company (20%). The file provided patients with the information they wanted in 79% of cases and allowed them to sue the physician in 12%. Only a quarter of the persons requesting files met with the physician concerned before making their request. CONCLUSION: The disclosure of secret medical information can lead to serious consequences to patients, of which they are not necessarily aware. This may require that clear information about patient-doctor confidentiality be provided to persons requesting files.

Amiodarone-related acute respiratory distress syndrome following sudden withdrawal of steroids.

Acute lung toxicity is a rare but classical complication of amiodarone therapy. We report the case of a patient who developed an optic neuropathy after 15 years of amiodarone administration, and who was treated for 2 weeks with steroids. Following withdrawal of steroids, the patient rapidly developed an acute respiratory distress syndrome. Postmortem lung histologic examination was consistent with amiodarone-induced pneumonitis. Since this complication is thought to be of immunological origin, we speculate that the sudden withdrawal of steroids was implicated in the development of the acute lung injury.

Myocardial injury in critically ill patients: relation to increased cardiac troponin I and hospital mortality.

OBJECTIVE: To examine the relationship between myocardial injury, assessed by cardiac troponin I (cTnI) levels, and outcome in selected critically ill patients without acute coronary syndromes or cardiac dysfunction. DESIGN AND SETTING: Prospective, observational study in the emergency ICU of a university teaching hospital. POPULATION: Over a 6-month period, 217 consecutive patients admitted to the ICU were studied. METHODS AND RESULTS: cTnI assays were performed in all patients on admission to the ICU. The incidence of myocardial injury, defined by cTnI level > 0.1 ng/mL, was 32% (69 of 217 patients). Overall mortality was 27% (58 of 217 patients). Patients with myocardial injury had a mortality rate of 51%, compared with only 16% mortality for those without myocardial injury (p < 0.001). The hospital mortality rate was highest among older patients (71 +/- 14% vs 58.5 +/- 20%, p < 0.0001) and patients with higher simplified acute physiology scale (SAPS) II score (62 +/- 25% vs 37 +/- 17%, p < 0.0001). Mechanical ventilation was associated with higher in-hospital death (50% vs 31%, for patients who died in the hospital vs those who were discharged alive; p = 0.03). Elevated blood levels of cTnI were found to be independently associated with hospital mortality, regardless of the presence of SAPS II score and mechanical ventilation, in the logistic regression analysis (odds ratio, 2.09; 95% confidence interval, 1.06 to 4.11; p = 0.01). CONCLUSIONS: This study demonstrates the high frequency of myocardial injury (32%) in critically ill patients without acute coronary syndromes or cardiac dysfunction on admission to ICU. Myocardial injury is an independent determinant of hospital mortality. Assessment of myocardial injury on admission to ICU would make it possible to identify patients at increased risk of death.

Candida spp. colonization significance in critically ill medical patients: a prospective study.

OBJECTIVE: Multiple-site colonization with Candida species is commonly recognized as a major risk factor for invasive fungal infection in critically ill patients. The fungal colonization density could be of predictive value for the diagnosis of systemic candidiasis in high-risk surgical patients. Little is known about it in the medical ICU setting. DESIGN AND SETTING: Prospective observational study in the eight-bed medical intensive care unit of a teaching hospital. SUBJECTS: 92 consecutive nonneutropenic patients hospitalized for more than 7 days. MEASUREMENTS AND RESULTS: The colonization index (ratio of the number of culture-positive surveillance sites for Candida spp. to the number of sites cultured) was calculated weekly upon ICU admission until death or discharge. The 0.50 threshold was reached in 36 (39.1%) patients, almost exclusively in those with detectable fungal colonization upon ICU admission. The duration of broad-spectrum antibiotic therapy was found to be the main factor that independently promoted fungal growth as measured through the colonization index. CONCLUSIONS: Candida spp. multiple-site colonization is frequently met among the critically ill medical patients. Broad-spectrum antibiotic therapy was found to promote fungal growth in patients with prior colonization. Since most of the invasive candidiasis in the ICU setting are thought to be subsequent to colonization in high-risk patients, reducing antibiotic use could be useful in preventing fungal infections.

Candidemia in critically ill patients: difference of outcome between medical and surgical patients.

OBJECTIVE: Candidemia is increasingly encountered in critically ill patients with a high fatality rate. The available data in the critically ill suggest that patients with prior surgery are at a higher risk than others. However, little is known about candidemia in medical settings. The main goal of this study was to compare features of candidemia in critically ill medical and surgical patients. DESIGN: Ten-year retrospective cohort study (1990-2000). SETTING: Medical and surgical intensive care units (ICUs) of a teaching hospital. PATIENTS: Fifty-one patients with at least one positive blood culture for Candida species. MAIN RESULTS: Risk factors were retrieved in all of the patients: central venous catheter (92.1%), mechanical ventilation (72.5%), prior bacterial infection (70.6%), high fungal colonization index (45.6%). Candida albicans accounts for 55% of all candidemia. The overall mortality was 60.8% (85% and 45.2% in medical and surgical patients, respectively). Independent factors associated with survival were prior surgery (hazard ratio [HR] =0.25; 0.09-0.67 95% confidence interval [CI], p<0.05), antifungal treatment (HR =0.11; 0.04-0.30 95% CI, p<0.05) and absence of neutropenia (HR =0.10; 0.02-0.45 95% CI, p<0.05). Steroids, neutropenia and high density of fungal colonization were more frequently found among medical patients compared to surgical ones. CONCLUSIONS: Candidemia occurrence is associated with a high mortality rate among critically ill patients. Differences in underlying conditions could account for the poorer outcome of the medical patients. Screening for fungal colonization could allow identification of such high-risk patients and, in turn, improve outcome.

An unusual cause of acute respiratory distress in a patient with AIDS: primary infection with Toxoplasma gondii.

Hypoxemic pneumonia in AIDS patients is mainly caused by Pneumocystis carinii, Toxoplasma gondii and CMV, although the significance of CMV recovery in BALF is often unclear. Since lung involvement generally occurs during reactivation, T. gondii is not expected to be demonstrated in patients without evidence of past infection with this agent. We report a fatal case of pneumonia revealing a T. gondii primary infection diagnosed thanks to the PCR analysis of the BALF.