Impact of extracorporeal membrane oxygenation (ECMO) support on piperacillin exposure in septic patients: a case-control study.

OBJECTIVES: To describe the impact of extracorporeal membrane oxygenation (ECMO) devices on piperacillin exposure in ICU patients. METHODS: This observational, prospective, multicentre, case-control study was performed in the ICUs of two tertiary care hospitals in France. ECMO patients with sepsis treated with piperacillin/tazobactam were enrolled. Control patients were matched according to SOFA score and creatinine clearance. The pharmacokinetics of piperacillin were described based on a population pharmacokinetic model, calculating the proportion of time the piperacillin plasma concentration was above 64 mg/L (i.e. 4× MIC breakpoint for Pseudomonas aeruginosa). RESULTS: Forty-two patients were included. Median (IQR) age was 60 years (49-66), SOFA score was 11 (9-14) and creatinine clearance was 47 mL/min (5-95). There was no significant difference in the proportion of time piperacillin concentrations were ≥64 mg/L in patients treated with ECMO and controls during the first administration (P = 0.184) or at steady state (P = 0.309). Following the first administration, 36/42 (86%) patients had trough piperacillin concentrations <64 mg/L. Trough concentrations at steady state were similar in patients with ECMO and controls (P = 0.535). Creatinine clearance ≥40 mL/min was independently associated with piperacillin trough concentration <64 mg/L at steady state [OR = 4.3 (95% CI 1.1-17.7), P = 0.043], while ECMO support was not [OR = 0.5 (95% CI 0.1-2.1), P = 0.378]. CONCLUSIONS: ECMO support has no impact on piperacillin exposure. ICU patients with sepsis are frequently underexposed to piperacillin, which suggests that therapeutic drug monitoring should be strongly recommended for severe infections.

Characteristics and outcome of varicella-zoster virus central nervous system infections in adults.

We conducted an observational retrospective study of all adults hospitalized for documented varicella-zoster virus (VZV) meningitis or encephalitis during years 2000-2015 in one referral centre. Thirty-six patients (21 males, 15 females) were included, with meningitis (n = 21), or meningoencephalitis (n = 15). Median age was 51 years [interquartile range, 35-76], and 6 patients (17%) were immunocompromised. Aciclovir was started in 32 patients (89%), with a median dose of 11 mg/kg/8 h [10-15]. No patient died, but 12 (33%) had neurological sequelae at discharge. Age was the only variable associated with adverse outcome (OR 1.98 [1.17-3.35] per 10-year increment, P = 0.011).

Determinants and consequences of positive valve culture when cardiac surgery is performed during the acute phase of infective endocarditis.

The optimal timing of cardiac surgery in infective endocarditis (IE) remains debated: Early surgery decreases the risk of embolism, and heart failure, but is associated with an increased rate of positive valve culture. To determine the determinants, and the consequences, of positive valve culture when cardiac surgery is performed during the acute phase of IE, we performed a retrospective study of adult patients who underwent cardiac surgery for definite left-sided IE (Duke Criteria), in two referral centres. During the study period (2002-2016), 148 patients fulfilled inclusion criteria. Median age was 65 years [interquartile range, 53-73], male-to-female ratio was 2.9 (110/38). Cardiac surgery was performed after 14 days [5-26] of appropriate antibiotics. Valve cultures returned positive in 46 cases (31.1%). Factors independently associated with positive valve culture were vegetation size ≥ 10 mm (OR 2.83 [1.16-6.89], P = 0.022) and < 14 days of appropriate antibacterial treatment before surgery (OR 4.68 [2.04-10.7], P < 0.001). Positive valve culture was associated with increased risk of postoperative acute respiratory distress syndrome (37.0% vs. 15.7%, P = 0.008) but was associated neither with an increased risk of postoperative relapse nor with the need for additional cardiac surgery. Duration of appropriate antibacterial treatment and vegetation size are independently predictive of positive valve culture in patients operated during the acute phase of IE. Positive valve culture is associated with increased risk of postoperative acute respiratory distress syndrome.

Mupirocin/chlorexidine to prevent methicillin-resistant Staphylococcus aureus infections: post hoc analysis of a placebo-controlled, randomized trial using mupirocin/chlorhexidine and polymyxin/tobramycin for the prevention of acquired infections in intubated patients.

PURPOSE: The reduction in acquired infections (AI) due to methicillin-resistant Staphylococcus aureus (MRSA) with the mupirocin/chlorhexidine (M/C) decontamination regimen has not been well studied in intubated patients. We performed post hoc analysis of a prior trial to assess the impact of M/C on MRSA AI and colonization. METHODS: We conducted a multicenter, placebo-controlled, randomized, double-blind study with the primary aim to reduce all-cause AI. The two regimens used [topical polymyxin and tobramycin (P/T), nasal mupirocin with chlorhexidine body wash (M/C), or corresponding placebos for each regimen] were administered according to a 2 × 2 factorial design. Participants were intubated patients in the intensive care units of three French university hospitals. The patients enrolled in the study (n = 515) received either active P/T (n = 130), active M/C (n = 130), both active regimens (n = 129), or placebos only (n = 126) for the period of intubation and an additional 24 h. The incidence and incidence rates (per 1,000 study days) of MRSA AI were assessed. Due to the absence of a statistically significant interaction between the two regimens, analysis was performed at the margins by comparing all patient receiving M/C (n = 259) to all patients not receiving M/C (n = 256), and all patients receiving P/T (n = 259) to all patients not receiving P/T (n = 256). RESULTS: Incidence [odds ratio (OR) 0.39, 95 % confidence interval (CI) (0.16-0.96), P = 0.04] and incidence rates [incidence rate ratio (IRR) 0.41, 95 % CI 0.17-0.97, P = 0.05] of MRSA AI were significantly lower with the use of M/C. We also observed an increase in the incidence (OR 2.50, 95 % CI 1.01-6.15, P = 0.05) and the incidence rate (IRR 2.90, 95 % CI 1.20-8.03, P = 0.03) of MRSA AI with the use of P/T. CONCLUSION: Among our study cohort of intubated patients, the use of M/C significantly reduced MRSA AI.

[Ventilator-induced immune dysfunction]. / Dysfonction immunitaire induite par la ventilation mécanique.

Although mechanical ventilation is an essential support in patients admitted to the intensive care unit, clinical and experimental studies have shown that it could be harmful and could induce lung injury. Pulmonary and immune cells can convert mechanical stimuli into biological signals that will lead to inflammation. This sterile inflammation both locally and systemically will cause immunosuppression.

Rhombencephalitis caused by Francisella tularensis.

Common presentations of tularemia include pneumonia and ulceroglandular, oropharyngeal, or typhoidal disease. Neuromeningeal involvement is extremely rare. We report a case of a severe rhombencephalitis due to Francisella tularensis. Diagnosis was possible thanks to a very precise interview, and the patient dramatically improved after specific antibiotherapy.

Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia.

The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.

Distinctive features between community-acquired pneumonia (CAP) due to Chlamydophila psittaci and CAP due to Legionella pneumophila admitted to the intensive care unit (ICU).

The spectrum of community-acquired pneumonia (CAP) due to Chlamydophila psittaci ranges from mild, self-limited CAP, to acute respiratory failure. We performed a retrospective study of 13 consecutive patients with CAP due to C. psittaci and 51 patients with legionellosis admitted in one intensive care unit (ICU) (1993-2011). As compared to patients with legionellosis, patients with psittacosis were younger (median age 48 [38-59] vs. 60 [50-71] years, p = 0.007), less frequently smokers (38 vs. 79 %, p < 0.001), with less chronic disease (15 vs. 57 %, p = 0.02), and longer duration of symptoms before admission (median 6 [5-13] vs. 5 [3-7] days, p = 0.038). They presented with lower Simplified Acute Physiology Score II (median 28 [19-38] vs. 39 [28-46], p = 0.04) and less extensive infiltrates on chest X-rays (median 2 [1-3] vs. 3 [3-4] lobes, p = 0.007). Bird exposure was mentioned in 100 % of psittacosis cases, as compared to 5.9 % of legionellosis cases (p < 0.0001). Extrapulmonary manifestations, biological features, and mortality (15.4 vs. 21.6 %, p = 0.62) were similar in both groups. In conclusion, severe psittacosis shares many features with severe legionellosis, including extrapulmonary manifestations, biological features, and outcome. Psittacosis is an important differential diagnosis for legionellosis, especially in cases of bird exposure, younger age, and more limited disease progression over the initial few days.

[Pulmonary manifestations induced by osimertinib]. / Toxicité pulmonaire induite par l'osimertinib.

INTRODUCTION: The third-generation tyrosine kinase inhibitor (TKI) osimertinib is recommended as a first-line treatment in advanced non-small cell lung cancer harboring an activating mutation of Epidermal Growth Factor Receptor (EGFR). Adverse pulmonary events related to osimertinib exposure have been reported, primarily in Japanese patients. They rarely occur in the Caucasian population. OBSERVATION: Herein we report two clinical cases of osimertinib-induced lung toxicities in patients diagnosed with advanced lung adenocarcinoma harboring an EGFR mutation. In the first case, interstitial pneumonia was asymptomatic and evolved favorably after osimertinib discontinuation. The second patient presented a more extensive form of lung injuries and despite systemic corticosteroid therapy, the evolution was fatal. CONCLUSION: Osimertinib-related lung toxicities remain exceptional. While most forms are mild, consideration of TKI treatment discontinuation may be necessitated. Introduction of another TKI or rechallenge with osimertinib might be considered along with corticosteroid therapy if necessary. Diffuse alveolar damage is a pejorative prognostic factor.

[Long term survival in chronic obstructive pulmonary disease after ventilation in intensive care]. / Survie à long terme des bronchopathes chroniques obstructifs après la réanimation.

OBJECTIVE: To compare the one year survival after discharge from ICU of patients with chronic obstructive pulmonary disease (COPD) admitted for acute hypercapnic respiratory failure and who required mechanical ventilation. METHODS: Retrospective cohort study on 130 patients, 52 patients were treated with non-invasive ventilation (NIV) and 78 patients with conventional mechanical ventilation (CMV). RESULTS: In 73 patients the cause for respiratory failure could not be identified. Long-term survival was significantly better following NIV than with CMV (p=0.02 by log-rank testing), but the better prognosis associated with use of NIV was not found in patients with no documented cause for the respiratory failure. After adjusting for male gender, age>65 years, simplified acute physiology score II>35, prior long-term home oxygen therapy, treatment with steroids, FEV1<30% of predicted value, body-mass index<21 kg/m2, albumin level<30 g/L, right ventricular failure, ventilator-associated pneumonia and cause of respiratory failure, NIV remained independently associated with better outcomes (adjusted hazard ratio 0.55; 95% CI 0.31-0.97; p=0.04). CONCLUSIONS: Our results suggest that in COPD patients requiring mechanical ventilation and who survived after an ICU stay, the use of NIV is an independent factor associated with a better long-term survival, especially in those with a documented cause of respiratory failure.

Hemorrhage increases cytokine expression in lung mononuclear cells in mice: involvement of catecholamines in nuclear factor-kappaB regulation and cytokine expression.

The expression of proinflammatory and immunoregulatory cytokines rapidly increases in the lungs after hemorrhage, and such alterations contribute to the frequent development of acute inflammatory lung injury in this setting. Blood loss also produces elevations in catecholamine concentrations in the pulmonary and systemic circulation. In the present experiments, we used alpha- and beta-adrenergic receptor blockade to examine in vivo interactions between hemorrhage-induced adrenergic stimulation and pulmonary cytokine expression. Treatment of mice with the alpha-adrenergic receptor antagonist phentolamine prevented not only the elevation in mRNA levels of IL-1beta, TNF-alpha, and TGF-beta1, the increase in IL-1beta protein, but also the activation of nuclear factor (NF)-KB and cyclic AMP response element binding protein, which occurred in lung cells of untreated animals during the first hour after hemorrhage. In contrast, treatment before hemorrhage with the beta-adrenergic receptor antagonist propranolol was associated with increases in mRNA levels for IL-1beta, TNF-alpha, and TGF-beta1, which were greater than those present in untreated hemorrhaged mice, and did not prevent hemorrhage-associated increases in lung IL-1beta protein. Treatment with propranolol prevented hemorrhage-induced phosphorylation of cyclic AMP response element binding protein, but increased hemorrhage-associated activation of NF-KB. These results demonstrate that hemorrhage initially increases pulmonary cytokine expression through alpha- but not beta-adrenergic stimulation, and suggest that such alpha-adrenergic-mediated effects occur through activation of the transcriptional regulatory factor NF-kappaB.

Use of high-performance liquid chromatography (HPLC) to monitor beta-lactam plasma concentrations during the treatment of endocarditis.

Guidelines recommend high doses of beta-lactams for the therapy of endocarditis. This report describes a retrospective study of 15 endocarditis patients (median age 64 years), treated according to guidelines, whose beta-lactam trough plasma concentrations were measured with high-performance liquid chromatography because of tolerance or efficacy concerns. For amoxycillin, the mean level was 86.8 mg/L (range: 30-212 mg/L); five (45%) patients had concentrations > 1000 x MIC. For cloxacillin, the mean level was 47.9 mg/L (range: 16.7-104 mg/L). The consequences of high and unpredicted beta-lactam trough plasma concentrations for a prolonged period have not yet been thoroughly evaluated.

[Parapneumonic pleural effusions: Epidemiology, diagnosis, classification and management]. / Les épanchements pleuraux parapneumoniques: épidémiologie, diagnostic, classification, traitement.

Parapneumonic pleural effusions represent the main cause of pleural infections. Their incidence is constantly increasing. Although by definition they are considered to be a "parapneumonic" phenomenon, the microbial epidemiology of these effusions differs from pneumonia with a higher prevalence of anaerobic bacteria. The first thoracentesis is the most important diagnostic stage because it allows for a distinction between complicated and non-complicated parapneumonic effusions. Only complicated parapneumonic effusions need to be drained. Therapeutic evacuation modalities include repeated therapeutic thoracentesis, chest tube drainage or thoracic surgery. The choice of the first-line evacuation treatment is still controversial and there are few prospective controlled studies. The effectiveness of fibrinolytic agents is not established except when they are combined with DNase. Antibiotics are mandatory; they should be initiated as quickly as possible and should be active against anaerobic bacteria except for in the context of pneumococcal infections. There are few data on the use of chest physiotherapy, which remains widely used. Mortality is still high and is influenced by underlying comorbidities.

NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome.

Activation of the nuclear regulatory factor NF-kappaB occurs in the lungs of patients with the acute respiratory distress syndrome (ARDS) and may contribute to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in this setting. Because of the important role that NF-kappaB activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kapppaB counterregulatory mechanisms, involving IkappaB proteins, in alveolar macrophages obtained from 7 control patients without lung injury and 11 patients with established ARDS. Cytoplasmic levels of the NF-kappaB subunits p50, p65, and c-Rel were significantly decreased in alveolar macrophages from patients with ARDS, consistent with enhanced migration of liberated NF-kappaB dimers from the cytoplasm to the nucleus. Cytoplasmic and nuclear levels of IkappaBalpha were not significantly altered in alveolar macrophages from patients with established ARDS, compared with controls. In contrast, nuclear levels of Bcl-3 were significantly decreased in patients with ARDS compared with controls (P = 0.02). No IkappaBgamma, IkappaBbeta, or p105 proteins were detected in the cytoplasm of alveolar macrophages from control patients or patients with ARDS. The presence of activated NF-kappaB in alveolar macrophages from patients with established ARDS implies the presence of an ongoing stimulus for NF-kappaB activation. In this setting, appropriate counterregulatory mechanisms to normalize nuclear levels of NF-kappaB and to suppress NF-kappaB-mediated transcription, such as increased cytoplasmic and nuclear IkappaBalpha levels or decreased Bcl-3 levels, appeared to be induced. Nevertheless, even though counterregulatory mechanisms to NF-kappaB activation are activated in lung macrophages of patients with ARDS, NF-kappaB remains activated. These results suggest that fundamental abnormalities in transcriptional mechanisms involving NF-kappaB and important in the inflammatory response occur in the lungs of patients with ARDS.

Acute nondilated anuric obstructive nephropathy on echography: difficult diagnosis in the intensive care unit.

Renal echography (RE) is a well recognized, accurate, non-invasive imaging procedure for detecting urinary tract (UT) obstruction in Intensive Care Unit (ICU) patients: a dilated collecting system is usually present but a few cases of nondilated obstructive nephropathy have been previously described. We report the clinical, biological, imaging procedure data and outcome of 6 additional cases of anuric obstructive nephropathy without dilatation on one or more RE. All patients had previous and/or actual history suggestive of UT obstruction. Retrograde ureteropyelography (RUP) was performed in all of them: it provided the diagnosis of obstruction in 4 and was immediately followed by dramatic improvement of renal function in all, including the 2 patients with septic shock from proven or suspected UT origin. The cause of obstruction was a neoplastic retroperitoneal process in 4. We conclude that anuric nondilated obstructive renal failure is not uncommon and should be considered in anuric patients when UT obstruction is likely to occur. The sole visualization of a non-dilated collecting system on RE should lead to repeat RE, especially in hypovolemic anuric patients. RUP provided immediate diagnostic and therapeutic benefits in comparison with other imaging procedures in our series.

Effects of epinephrine on right ventricular function in patients with severe septic shock and right ventricular failure: a preliminary descriptive study.

OBJECTIVE: To recognize patients with unresponsive septic shock and right ventricular (RV) failure and to evaluate the effects of epinephrine on RV performance in these patients. DESIGN: Prospective descriptive study. SETTING: Medical intensive care unit. SUBJECTS: 14 consecutive patients in septic shock unresponsive to fluid loading, dopamine, and dobutamine. INTERVENTIONS: Evaluation of RV function by thermodilution with a pulmonary artery catheter equipped with a rapid-response thermistor. Measurements were obtained before and during epinephrine infusion to achieve a systolic arterial pressure > or = 90 mmHg or a mean arterial pressure (MAP) > or = 70 mmHg. RESULTS: At the time of inclusion in the study the hemodynamic pattern in the 14 patients was as follows: (MAP) 58 +/- 14 mmHg, systemic vascular resistance (SVR) 1046 +/- 437 dyne.s.cm-5.m-2, pulmonary artery occlusion pressure (PAOP) 14 +/- 4 mmHg, mean pulmonary artery pressure (MPAP) 24 +/- 4 mmHg, right arterial pressure (RAP) 11 +/- 4 mmHg, cardiac index (CI) 4 +/- 1.7 l/min per m2. During epinephrine infusion, MAP, CI and stroke volume index (SVI) were increased (27%, p < 0.01; 20%, p < 0.01; 15%, p < 0.05, respectively). There was no change in PAOP, SVR or heart rate. Seven patients (group A) had marked RV failure defined by both RV dilation [RV end-diastolic volume index (RVEDVI) > 92 ml/m2] and low RV ejection factor (RVEF) (< 52%) and 7 did not (group B). Group A had a lower baseline RVEF than group B (24 +/- 7 vs 45 +/- 9%, p < 0.05), a higher RVEDVI (134 +/- 28 vs 79 +/- 17 ml/ m2, p < 0.01), and a higher RVES (systolic) VI (103 +/- 30 vs 43 +/- 11 ml/ m2, p < 0.01). The other hemodynamics, especially RAP and RV stroke work index (RVSWI) were no different in the two groups and did not predict RV dysfunction. In group A, epinephrine infusion improved RVEF (25%, p < 0.05) by a reduction in RVESVI (-8%, p < 0.05) without any change in RVEDVI or in RAP, in spite of a rise in MPAP (11%, p < 0.05). A rise in RVSWI (76%, p < 0.05), SVI (23%, p < 0.05), and CI (24%, p < 0.05) was also achieved. An upward vertical shift of the Frank-Starling relationship RVSWI/ RVEDVI and an upward shift to the left of the pressure volume relationship pulmonary artery peak pressure/RVESVI was observed only in the group with RV failure following treatment with epinephrine. In group B (without RV failure), RV parameters were not modified by epinephrine. CONCLUSION: In patients with severe septic shock, RV dysfunction was identified by the use of an RVEF pulmonary artery catheter and was improved by epinephrine by means of an improvement in RV contractility.

Trial of dexamethasone treatment for severe bacterial meningitis in adults. Adult Meningitis Steroid Group.

OBJECTIVE: To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults. DESIGN: Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30. RESULTS: Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion. CONCLUSION: Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae.

Procalcitonin: a valuable indicator of infection in a medical ICU?

OBJECTIVE: To assess the use of procalcitonin (PCT) for the diagnosis of infection in a medical ICU. DESIGN: Prospective, observational study. PATIENTS: Seventy-seven infected patients and 24 patients with systemic inflammatory response syndrome (SIRS) due to other causes. Seventy-five patients could be classified into sepsis (n = 24), severe sepsis (n = 27) and septic shock (n = 24), and 20 SIRS patients remained free from infection during the study. Plasma PCT and C-reactive protein (CRP) levels were evaluated within 48 h of admission (day 0), at day 2 and day 4. RESULTS: As compared with SIRS, PCT and CRP levels at day 0 were higher in infected patients, regardless of the severity of sepsis (25.2 +/- 54.2 ng/ml vs 4.8 +/- 8.7 ng/ml; 159 +/- 92 mg/l vs 71 +/- 58 mg/l, respectively). At cut-off values of 2 ng/ml (PCT) and 100 mg/l (CRP), sensitivity and specificity were 65% and 70% (PCT), 74% and 74% (CRP). PCT and CRP levels were significantly more elevated in septic shock (38.5 +/- 59.1 ng/ml and 173 +/- 98 mg/l) than in SIRS (3.8 +/- 6.9 ng/ml and 70 +/- 48 mg/l), sepsis (1.3 +/- 2.7 ng/ml and 98 +/- 76 mg/l) and severe sepsis (9.1 +/- 18. 2 ng/ml and 145 +/- 70 mg/l) (all p = 0.005). CRP, but not PCT, levels were more elevated in severe sepsis than in SIRS (p<0.0001). Higher PCT levels in the patients with four dysfunctional organs and higher PCT and CRP levels in nonsurvivors may only reflect the marked inflammatory response to septic shock. CONCLUSION: In this study, PCT and CRP had poor sensitivity and specificity for the diagnosis of infection. PCT did not clearly discriminate SIRS from sepsis or severe sepsis.