Fabrice Zeni

High Sensitivity and Specificity of Serum Procalcitonin Levels in Adults with Bacterial Meningitis

It was shown in children that serum procalcitonin was the best marker to use to differentiate bacterial from viral meningitis. To evaluate procalcitonin in the diagnosis of acute bacterial and viral meningitis, we conducted a prospective study including adult patients who were suspected of having meningitis and who were admitted to an emergency department. Cerebrospinal fluid (CSF) and serum levels of procalcitonin were measured in 105 consecutive patients. The diagnosis of meningitis was based on clinical findings, gram staining, culture, and chemical analysis of CSF. Twenty-three patients had bacterial meningitis, 57 had viral meningitis, and 25 did not have meningitis. Bacteriologic and chemical analysis of CSF did not allow correct differentiation of viral from bacterial meningitis. On the other hand, a serum procalcitonin level >0.2 ng/mL had a sensitivity and specificity of up to 100% in the diagnosis of bacterial meningitis. Serum procalcitonin levels seem to be the best marker in differentiating between bacterial and viral meningitis in adults.

Prospective study of nosocomial colonization and infection due to Pseudomonas aeruginosa in mechanically ventilated patients

Abstract. Objective: To investigate the respective contribution of endogenous and exogenous transmission of Pseudomonas aeruginosa in the colonization of lungs in the mechanically ventilated patient, to estimate the role of P. aeruginosa colonization in the occurrence of severe infections, and to extrapolate appropriate control measures for the prevention of P. aeruginosa ventilator-associated pneumonia. Design: Prospective study of the presence of P. aeruginosa (in stomach fluid, throat specimens, stool, and sputum) on admission, twice a week throughout the patients stay, and in their environment. O-serotyping, pulsed-field gel electrophoresis, and arbitrarily-primed polymerase chain reaction were used to characterize the strains. Setting: The two intensive care units (ICUs 1 and 2) of a university hospital. Patients: During a 6-month period, 59 patients were included (21 in ICU 1 and 38 in ICU 2). Results: P. aeruginosa was isolated in 26 patients, including ten pneumonia cases and seven colonizations on admission. The incidence of acquired colonization was statistically different between the two ICUs: 5.5 and 20.5 per 1000 days of mechanical ventilation, in ICUs 1 and 2, respectively. Endogenous acquisition was the main origin of P. aeruginosa colonization (21 of 26 patients) and the upper respiratory tract was the main bacterial reservoir in broncho-pulmonary colonization and infection. However, during the 6-month period of the study, a multidrug-resistant strain of P. aeruginosa O:11, isolated in the sink of the room of 12 patients, was found responsible for two colonizations (1 digestive, 1 throat/lungs) and one pneumonia. As a whole, from 26 cases of colonization/infection with P. aeruginosa, 5 were related to an exogenous contamination (environmental reservoir in 4 patients and cross-contamination in one patient). Conclusions: These results emphasize the need for applying various infection control measures to prevent colonization of patients with P. aeruginosa, including strategies to limit the potential of sinks from acting as a source or reservoir for this bacterium.

Renal perfusion assessment by renal Doppler during fluid challenge in sepsis.

Objectives:To assess renal resistive index variations in response to fluid challenge. Design:Prospective cohort study. Setting:Three ICUs in French teaching hospitals. Patients:Consecutive patients receiving mechanical ventilation and requiring a fluid challenge. Intervention:Resistive index measurement before and after fluid challenge. Measurements and Main Results:Renal Doppler was used to measure resistive index and esophageal Doppler to monitor aortic blood flow. Of the 35 included patients, 17 (49%) met our definition for fluid challenge responsiveness, that is, had at least a 10% increase in aortic blood flow. After fluid challenge, mean arterial pressure increased from 73 mm Hg (interquartile range 68–79) to 80 mm Hg (75–86; p < 0.0001) and stroke volume from 50 mL (30–77) to 55 mL (39–84; p < 0.0001). Stroke volume changes after fluid challenge were +28.6% (+18.8% to +38.8%) in fluid challenge responders and +3.1% (–1.6% to 7.4%) in fluid challenge nonresponders. Renal resistive index was unchanged after fluid challenge in both nonresponders (0.72 [0.67–0.75] before and 0.71 [0.67–0.75] after fluid challenge; p = 0.62) and responders (0.70 [0.65–0.75] before and 0.72 [0.68–0.74] after fluid challenge; p = 0.11). Stroke volume showed no correlations with resistive index changes after fluid challenge in the overall population (r2 = 0.04, p = 0.25), in fluid challenge responders (r2 = –0.02, p = 0.61), or in fluid challenge nonresponders (r2 = 0.08, p = 0.27). Stroke volume did not correlate with resistive index changes after fluid challenge in the subgroups without acute kidney injury (AKIN definition), with transient acute kidney injury, or with persistent acute kidney injury. Conclusion:Systemic hemodynamic changes induced by fluid challenge do not translate into resistive index variations in patients without acute kidney injury, with transient acute kidney injury, or with persistent acute kidney injury.

Can emergency physicians identify a high mortality subgroup of patients with sepsis: role of procalcitonin.

Objective To assess the potential role of procalcitonin and tumor necrosis factor-&agr;, interleukin-6 and interleukin-8, in the prognosis of patients with sepsis. Design Prospective study. Setting The emergency unit of a teaching hospital. Patients We included 131 patients with sepsis: 15 (12%) with septic shock, 20 (15%) with severe sepsis and 96 (73%) with sepsis. Measurements and main results Out of the 131 patients, 112 (85.5%) survived and 19 (14.5%) died. These two groups of patients differed with regard to simplified acute physiology score II, severity of infectious disease and underlying disease, bacteremia and type of microorganisms. The mean serum levels of tumor necrosis factor, interleukin-6, interleukin-8, procalcitonin and lactates at study entry were higher in nonsurvivors than in survivors. Multivariate regression analysis showed the most significant of these variables to be serum procalcitonin level (P=0.0007), simplified acute physiology score II (P=0.03) and serum lactate level (P=0.03). Using a model incorporating these three variables, with a cut-off value corresponding to a 15% probability of predicting mortality, death could be correctly predicted in 99.5% of cases and survival in 95%. This cut-off value allowed us to maximize the prediction of death. When serum procalcitonin levels were not taken into account, the best model included simplified acute physiology score II and serum lactate and interleukin-6 levels, but the rate of correct prediction of death then dropped to 84%. Conclusions Stepwise multivariate logistic regression analysis showed serum procalcitonin level to be a valuable marker of sepsis severity, compared with the 15 other clinical, biochemical and bacteriologic variables tested.

Decrease in serum procalcitonin levels over time during treatment of acute bacterial meningitis

IntroductionThe aim of this study was to describe the change in serum procalcitonin levels during treatment for community-acquired acute bacterial meningitis.MethodsOut of 50 consecutive patients presenting with bacterial meningitis and infection at no other site, and who had received no prior antibiotic treatment, 48 had a serum procalcitonin level above 0.5 ng/ml on admission and were enrolled in the study.ResultsThe mean age of the patients was 55 years, and mean Glasgow Coma Scale score on admission was 13. The time from symptom onset to admission was less than 24 hours in 40% of the patients, 24–48 hours in 20%, and more than 48 hours in 40%. The median (interquartile) interval between admission and initial antibiotic treatment was 160 min (60–280 min). Bacterial infection was documented in 45 patients. Causative agents included Streptococcus pneumoniae (n = 21), Neisseria meningitidis (n = 9), Listeria monocytogenes (n = 6), other streptococci (n = 5), Haemophilus influenzae (n = 2) and other bacteria (n = 2). The initial antibiotic treatment was effective in all patients. A lumbar puncture performed 48–72 hours after admission in 34 patients showed sterilization of cerebrospinal fluid. Median (interquartile) serum procalcitonin levels on admission and at day 2 were 4.5 (2.8–10.8) mg/ml and 2 (0.9–5.0) mg/ml, respectively (P < 0.0001). The corresponding values for C-reactive protein were 120 (21–241) mg/ml and 156 (121–240) mg/ml, respectively. Five patients (10%) died from noninfectious causes during their hospitalization.ConclusionsSerum procalcitonin levels decrease rapidly with appropriate antibiotic treatment, diminishing the value of lumbar puncture performed 48–72 hours after admission to assess treatment efficacy.

Continuous infusion of ceftazidime in critically ill patients undergoing continuous venovenous haemodiafiltration: pharmacokinetic evaluation and dose recommendation

IntroductionIn seriously infected patients with acute renal failure and who require continuous renal replacement therapy, data on continuous infusion of ceftazidime are lacking. Here we analyzed the pharmacokinetics of ceftazidime administered by continuous infusion in critically ill patients during continuous venovenous haemodiafiltration (CVVHDF) in order to identify the optimal dosage in this setting.MethodSeven critically ill patients were prospectively enrolled in the study. CVVHDF was performed using a 0.6 m2 AN69 high-flux membrane and with blood, dialysate and ultrafiltration flow rates of 150 ml/min, 1 l/hour and 1.5 l/hour, respectively. Based on a predicted haemodiafiltration clearance of 32.5 ml/min, all patients received a 2 g loading dose of ceftazidime, followed by a 3 g/day continuous infusion for 72 hours. Serum samples were collected at 0, 3, 15 and 30 minutes and at 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours; dialysate/ultrafiltrate samples were taken at 2, 8, 12, 24, 36 and 48 hours. Ceftazidime concentrations in serum and dialysate/ultrafiltrate were measured using high-performance liquid chromatography.ResultsThe mean (± standard deviation) elimination half-life, volume of distribution, area under the concentration-time curve from time 0 to 72 hours, and total clearance of ceftazidime were 4 ± 1 hours, 19 ± 6 l, 2514 ± 212 mg/h per l, and 62 ± 5 ml/min, respectively. The mean serum ceftazidime steady-state concentration was 33.5 mg/l (range 28.8–36.3 mg/l). CVVHDF effectively removed continuously infused ceftazidime, with a sieving coefficient and haemodiafiltration clearance of 0.81 ± 0.11 and 33.6 ± 4 mg/l, respectively.ConclusionWe conclude that a dosing regimen of 3 g/day ceftazidime, by continuous infusion, following a 2 g loading dose, results in serum concentrations more than four times the minimum inhibitory concentration for all susceptible pathogens, and we recommend this regimen in critically ill patients undergoing CVVHDF.

Transient and Persistent Acute Kidney Injury and the Risk of Hospital Mortality in Critically Ill Patients: Results of a Multicenter Cohort Study

Objective:To assess the prognostic impact of transient and persistent acute kidney injury in critically ill patients. Design:Retrospective analysis of prospectively collected patient data Setting:Six hospital ICUs. Patients:Critically-ill patients with ICU stay longer than three days. Intervention:None. Measurements and Main Results:Assessment of hospital survival with respect to acute kidney injury duration. A total of 447 patients were included in this study, including 283 patients (63.3%) with an acute kidney injury at admission (175 and 108 patients with persistent and transient acute kidney injury, respectively). Patients with persistent acute kidney injury more frequently had stage 3 acute kidney injury (42.9% vs 30.6%; p = 0.04). Hospital survival was 76.2% (n = 125) in patients without acute kidney injury, 70.4% (n = 76) in patients with transient acute kidney injury, and 61.1% (n = 107) in patients with persistent acute kidney injury. After adjustment for confounding factors, the factors associated with lower hospital survival were the need for vasopressors (odds ratio, 0.65; 95% CI, 0.43–0.98) and the presence of persistent acute kidney injury (odds ratio, 0.58; 95% CI, 0.36–0.95). When included in the final model, stage 3 acute kidney injury was independently associated with a lower hospital survival (odds ratio, 0.83; 95% CI, 0.70–0.98), and persistent acute kidney injury was no longer associated with outcome. Conclusion:Two thirds of the critically ill patients with acute kidney injury have persistent acute kidney injury. Although mortality increased progressively with the duration of acute kidney injury, we found no independent association between this duration and patient outcome when the acute kidney injury severity is taken into account. Our results suggest that the classical “prerenal acute kidney injury” and “acute tubular necrosis” paradigm might be of limited interest from a pathophysiological or prognostic point of view.

Diagnostic accuracy of early urinary index changes in differentiating transient from persistent acute kidney injury in critically ill patients: multicenter cohort study

IntroductionUrinary indices have limited effectiveness in separating transient acute kidneyinjury (AKI) from persistent AKI in ICU patients. Their time-course may vary withthe mechanism of AKI. The primary objective of this study was to evaluate thediagnostic value of changes over time of the usual urinary indices in separatingtransient AKI from persistent AKI.MethodsAn observational prospective multicenter study was performed in six ICUs involving244 consecutive patients, including 97 without AKI, 54 with transient AKI, and 93with persistent AKI. Urinary sodium, urea and creatinine were measured at ICUadmission (H0) and on 6-hour urine samples during the first 24 ICU hours (H6, H12,H18, and H24). Transient AKI was defined as AKI with a cause for renalhypoperfusion and reversal within 3 days.ResultsSignificant increases from H0 to H24 were noted in fractional excretion of urea(median, 31% (22 to 41%) and 39% (29 to 48%) at H24, P < 0.0001),urinary urea/plasma urea ratio (15 (7 to 28) and 20 (9 to 40), P <0.0001), and urinary creatinine/plasma creatinine ratio (50 (24 to 101) and 57 (29to 104), P = 0.01). Fractional excretion of sodium did not changesignificantly during the first 24 hours in the ICU (P = 0.13). Neitherurinary index values at ICU admission nor changes in urinary indices between H0and H24 performed sufficiently well to recommend their use in clinical setting(area under the receiver-operating characteristic curve ≤0.65).ConclusionAlthough urinary indices at H24 performed slightly better than those at H0 indifferentiating transient AKI from persistent AKI, they remain insufficientlyreliable to be clinically relevant.

Acute Respiratory Distress Syndrome and Risk of AKI among Critically Ill Patients

BACKGROUND AND OBJECTIVES Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded. RESULTS This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001). CONCLUSIONS ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.

Influence of early dysnatremia correction on survival of critically ill patients.

ABSTRACT Increasing evidence suggests that dysnatremia at intensive care unit (ICU) admission may predict mortality. Little information is available, however, on the potential effect of dysnatremia correction. This is an observational multicenter cohort study in patients admitted between 2005 and 2012 to 18 French ICUs. Hyponatremia and hypernatremia were defined as serum sodium concentration less than 135 and more than 145 mmol/L, respectively. We assessed the influence on day 28 mortality of dysnatremia correction by day 3 and of the dysnatremia correction rate. Of 7,067 included patients, 1,830 (25.9%) had hyponatremia and 634 (9.0%) had hypernatremia at ICU admission (day 1). By day 3, hyponatremia had been corrected in 1,019 (1,019/1,830; 55.7%) and hypernatremia in 393 (393/634; 62.0%) patients. After adjustment for confounders, persistent hyponatremia or hypernatremia on day 3 was independently associated with higher day 28 mortality (odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.06 – 1.61; and OR, 1.86; 95% CI, 1.37 – 2.54; respectively). Hyponatremia corrected by day 3, hypernatremia corrected by day 3, and ICU-acquired hyponatremia were not associated with day 28 mortality. Median correction rate from days 1 to 3 was 2.58 mmol/L per day (interquartile range, 0.67 – 4.55). Higher natremia correction rate was associated with lower crude and adjusted day 28 mortality rates (OR per mmol/L per day, 0.97; 95% CI, 0.94 – 1.00; P = 0.04; and OR per mmol/L per day, 0.93; 95% CI, 0.90 – 0.97; P = 0.0003, respectively). Our results indicate that dysnatremia correction is independently associated with survival, with the effect being greater with faster correction rates of up to 12 mmol/L per day.