Toxinotype A Clostridium perfringens causing septicaemia with intravascular haemolysis: two cases and review of the literature.

BACKGROUND: Septicaemia with intravascular haemolysis is a rare, but often fatal, presentation of Clostridium perfringens infection. C. perfringens is a Gram-positive, anaerobic bacterium that can produce multiple toxins. Toxinotyping is not performed regularly. METHODS: This article describes two human cases of C. perfringens infections. Toxinotyping was performed using polymerase chain reaction (PCR). Additionally, a structured review of the literature was performed which searched specifically for cases of C. perfringens infection with haemolysis. RESULTS: Both cases were identified as toxinotype A strains and both cases were fatal. Also, both cases showed marked haemolysis during their clinical course, which is assumed to have played a significant role in their outcome. In total, 83 references were identified describing human C. perfringens infection with haemolysis. Mortality rates have been stable over the last 10 years at 80%. Toxinotyping has been performed in a total of six cases. Of the four cases analysed by PCR, all were identified as toxinotype A. CONCLUSIONS: Haemolytic C. perfringens infections are rare but are fatal in most cases. Toxinotyping is performed rarely. The authors advocate increased use of toxinotyping to gain insight into pathophysiology and more effective interventions.

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Population pharmacokinetics of ceftriaxone administered as continuous or intermittent infusion in critically ill patients.

OBJECTIVES: To describe the population pharmacokinetics and protein-binding characteristics of unbound ceftriaxone administered as continuous or intermittent infusion. Additionally, to determine the optimal dosing regimen in critically ill patients. METHODS: A pharmacokinetic study was performed in the ICU of a tertiary teaching hospital. Patients were treated with ceftriaxone as continuous or intermittent infusion. A population pharmacokinetic model was developed with non-linear mixed-effects analysis. Subsequently, the PTA of a 100% T>MIC was assessed for influential patient characteristics using Monte Carlo simulation. RESULTS: Fifty-five patients were included. The pharmacokinetics of ceftriaxone was best described by a one-compartment model with non-linear saturable protein binding including the following covariates: body weight, estimated CLCR, serum albumin concentration and mode of administration. For pathogens with an MIC of 1 mg/L, the simulation demonstrated that intermittent infusion of 2 g/24 h only resulted in a ≥90% PTA in patients with a reduced CLCR (0-60 mL/min). Intermittent infusion of 2 g/12 h led to sufficient exposure if CLCR was 0-90 mL/min and continuous infusion of 2 g/24 h led to a ≥90% PTA in all simulations (CLCR 0-180 mL/min). CONCLUSIONS: In the critically ill, the clearance of unbound ceftriaxone is closely related to CLCR. Furthermore, ceftriaxone protein binding is saturable, variable and dependent on serum albumin concentration. Intermittent dosing of 2 g/24 h ceftriaxone leads to subtherapeutic exposure in patients with a normal or increased CLCR. Treating these patients with continuous infusion of 2 g/24 h is more effective than an intermittent dosing regimen of 2 g/12 h.

Major clinical events, signs and severity assessment scores related to actual survival in patients who died from primary biliary cirrhosis. A long-term historical cohort study.

BACKGROUND/AIMS: One of the prognostic methods for survival in primary biliary cirrhosis (PBC) is the Mayo model, with a time-scale limited to 7 years. The aim of our study was to assess how major clinical events, signs, several severity assessment methods and Mayo survival probabilities fit in with actual patient survival, by using yearly observations until 0.5 years before patient death from PBC. METHODOLOGY: Data of 32 patients dying from PBC were collected prior to death at -0.5, -1, -2 etc. years (median: -5 years, range: -16 to -0.5 years). Major events registered were: first occurrence of ascites, upper gastrointestinal bleeding or manifest hepatic encephalopathy and signs, first observation of spider naevi or purpura. Severity assessment methods applied (all with scores and classes) were: Mayo (M), Child-Campbell (C), Pugh-Child (P), Pugh-Child-PBC (PP), 'Child-Pugh' (CP), and Ascites Nutritional State-Child (ANS). Fifty percent survival estimates were calculated from Mayo scores. Severity assessment method variables were: ascites (C, P, PP, CP, ANS), encephalopathy (C, P, PP, CP), nutritional state (C, ANS), edema (M), age (M), serum albumin (M, C, P, PP, CP), bilirubin (C, M, P, PP, CP), and prothrombin time (M, P, PP, CP). RESULTS: In 27 out of 32 patients a major event occurred, always between -6 and -0.5 years (median: -1 year) and, never between -16 and -7 years (p < 0.0001). A sign was first observed in 30/32 between -14 and -0.5 years (median: -2 years). Compared to the total population, a sign, and even more so, an event indicated a shorter survival (p = 0.004 and p = 0.0002, respectively). The median 50% estimated survival (predicted by the Mayo model) fitted the actual survival from -6 to -0.5 years (r = -0.7, p < 0.0001), but not from -16 to -7 years (r = -0.1, p = 0.4). All -6 to -0.5-year severity scores correlated (p < 0.0001) both with actual survival (M, C, P, PP, and CP r = 0.7; ANS r = 0.5) and with estimated M 50% survival (C, P, PP, CP r = -0.9; ANS r = -0.6; M score: -0.99), but none with actual survival from -16 to -7 years, except for M, slightly (r = -0.3, p = 0.04). A nomogram for mean C, CP, M and ANS scores related to actual survival was constructed for the -6 to -0.5-year period. The C and CP classes A, B, and C did not appear to distinguish sufficiently into actual survival, whereas the M classes did. CONCLUSIONS: The occurrence of a major event appeared to exclude survival over 6 years. In these final 6 years, Child-Campbell, Mayo and Pugh scores correlated equally well with actual survival and better than Ascites/Nutritional State score. In our PBC patients, Campbell was an excellent alternative for Pugh; for Pugh, the original Child-Turcotte variable limits were fully sufficient.