Assessment of high-priced systemic antifungal prescriptions.

OBJECTIVES: To assess compliance with international guidelines for costly antifungal prescriptions and to compare these results with a first study performed in 2007. METHODS: Retrospective study including all costly antifungal prescriptions made in surgical and medical intensive care units and in a hepatobiliary, pancreatic, and digestive surgery unit. Prescriptions were assessed in terms of indication, dosage, and antifungal de-escalation. RESULTS: Seventy-four treatments were analyzed. Treatments were prescribed for prophylactic (1%), empirical (22%), pre-emptive (16%), or targeted therapy (61%). Caspofungin accounted for 68% of prescriptions, followed by voriconazole (20%) and liposomal amphotericin B (12%). Indication was appropriate in 91%, debatable in 1%, and inappropriate in 8%. Dosage was appropriate in 69%, debatable in 8%, and inappropriate in 23%. Prescriptions were inappropriate for the following reasons: lack of dosage adjustment in light of the hepatic function (10 cases), underdosage or excessive dosage by>25% of the recommended dose in seven cases. De-escalation to fluconazole was implemented in 40% of patients presenting with a fluconazole-susceptible candidiasis. CONCLUSION: The overall incidence of appropriate use was higher in 2012 compared with 2007 (62% and 37% respectively, P=0.004). Nevertheless, costly antifungal prescriptions need to be optimized in particular for empirical therapy, dosage adjustment, and potential de-escalation to fluconazole.

Combination of caspofungin and an azole or an amphotericin B formulation in invasive fungal infections.

OBJECTIVES: Combination of caspofungin and another anti-fungal agent raise expectation of improved efficacy in severe fungal infections including failures to first line therapy. METHODS: We assessed the efficacy and safety of a combination therapy including caspofungin in 17 immunosuppressed or postoperative patients progressive despite standard anti-fungal therapy. RESULTS: The infections included aspergillosis (6), invasive candidiasis (9), mucormycosis (1) and Scedosporium pneumonia (1). Infections had failed one to four prior lines of treatment. The anti-fungal agent combined to caspofungin was either an amphotericin B formulation or an azole. There were 12 favourable responses (71%) and five failures. The survival rate at 3 months was 47%. Eleven patients died within 2-533 days. The causes of death included the initial fungal infection (4), relapse of the infection after switching to oral monotherapy (2), breakthrough aspergillosis (1), and the underlying condition (4). Clinical and renal tolerance were good. Significant hepatic abnormalities were recorded in eight (50%) of the 16 patients evaluable for biological tolerance. CONCLUSION: Caspofungin combined with an azole or with amphotericin B may be of interest in the treatment of serious fungal infections after failure of conventional therapy. Close monitoring of hepatic function is required. These approach should be evaluated in prospective trials.

[A puzzling circulatory failure after total hip replacement]. / Un curieux choc vasoplégique après prothèse totale de la hanche.

The diagnosis of acute circulatory failure in the postoperative course of hip replacement must concentrate on frequent complications, but rare complications requiring specific treatment must also be diagnosed. We report on the occurrence of a case of acute adrenal insufficiency subsequent to enoxaparin-induced type II thrombocytopenia. A delay was necessary to establish a correct diagnosis for two reasons: (1) an unusual clinical presentation and (2) an underevaluation of the medical risk during the preoperative visit. The evolution was nevertheless favorable after prescription of steroids that had to be prescribed chronically.

Favorable outcome in a large left heart air embolism: lessons from an unusual complication of a noninvasive chest scan.

OBJECTIVE: To report an unusual life-threatening complication of the performance of a computed tomographic (CT) scan of the chest. DESIGN: Case report. SETTING: University hospital. PATIENT: An intubated patient with blunt thoracic trauma. INTERVENTION: Performance of a CT scan of the chest at full inspiration. MAIN RESULT: With air insufflation, a large left ventricular air embolism occurred as a consequence of an airway breach, revealed by the simultaneous existence of a mild bilateral anterior pneumothorax. CONCLUSION: CT scan of the chest in patients at risk of airway breach (patients with acute respiratory distress syndrome, trauma patients) should first be performed at full expiration, not full inspiration.

[Role of hygiene and bacteriological laboratories in the management of an epidemic of Enterobacter aerogenes multiresistant to antibiotics]. / Rôles des laboratoires d'hygiène et de bactériologie dans la prise en charge d'une épidémie à Enterobacter aerogenes multirésistant aux antibiotiques.

We describe a multiresistant Enterobacter aerogenes outbreak in an intensive care-unit. An epidemiology study based on phenotypic characters (species diagnosis and antibiotype) was completed by a genotypic study (pulsed field electrophoresis) to confirm bacterial clonality. The hygiene laboratory proposed numerous preventive measures to limit bacterial dispersion. We describe the role of bacteriologists, hygienists and medical staff to stop the bacterial dispersion.

Plasma cyclic GMP concentrations and their relationship with changes of blood pressure levels in pre-eclampsia.

BACKGROUND: One of the possible mechanisms responsible for pre-eclampsia is a loss of efficiency of the L-arginine-nitric oxide pathway with subsequent inactivation of the guanylyl cyclases of the vascular smooth muscle cells. As a result there should be a decrease in plasma cyclic 3'-5' guanosine monophosphate (cGMP) concentrations in pre-eclampsia. We assessed the behavior of this nucleotid in the plasma of pre-eclamptic women. SUBJECTS AND METHODS: Sixteen pre-eclamptic women, 16 normotensive pregnant women matched for gestational age and six nonpregnant controls were investigated. Arterial blood pressure was recorded at inclusion time and then once-a-day until the fourth day after delivery concomitantly with the collection of blood samples for determining plasma cGMP, atrial natriuretic peptides (ANP), creatinine, uric acid and platelet counts. Also 24 h urines were simultaneously collected to calculate renal clearance of cGMP. RESULTS: Before the initiation of antihypertensive treatment, plasma cGMP levels were significantly higher (p < 0.01) in pre-eclampsia women as compared both to pregnant normotensive controls and nonpregnant women (7.02 +/- 0.9 versus 4.8 +/- 0.76 versus 1.93 +/- 0.15 pmol.ml-1, p < 0.01). Under antihypertensive treatment, cGMP levels decreased significantly (p < 0.05) to 5.48 +/- 0.9 pmol.ml-1. The increase of plasma cGMP was associated with high ANP levels; the likelihood that a renal impairment could account for an increase in plasma cGMP was ruled out because the clearance of creatinine was not impaired. Similarly the possibility of a significant linear correlation between cGMP levels and blood pressure values or biological data was excluded in these women. CONCLUSION: Plasma cGMP concentrations are increased in pre-eclampsia. They decrease to control values when blood pressure returns to normal values; they indicate enhanced guanylyl cyclase activation by ANP and additional factors, but cannot be considered as a direct index of the severity of pre-eclampsia.

Plasma and urine concentrations of atropine after the ingestion of cooked deadly nightshade berries.

BACKGROUND: Adult intoxications due to ingestion of deadly nightshade berries is uncommon. CASE REPORTS: Collective intoxication of eight persons occurred after accidental ingestion of ripened Atropa belladonna berries. Three of the four adults displayed delirious states with visual hallucinations; one patient fell into a coma and required mechanical ventilation. Four children and one adult exhibited mild peripheral anticholinergic symptoms. Kinetic data were obtained on the three hospitalized adults. DISCUSSION: The optimal intensive care for such patients is discussed.

In vivo evidence of enhanced guanylyl cyclase activation during the hyperdynamic circulation of acute liver failure.

Nitric oxide and atrial natriuretic peptides are the main activators of guanylyl cyclases, which transform GTP into cyclic GMP and thereby contribute to the decrease of vascular tone. To investigate the increase, if any, of plasma cyclic GMP concentrations in human patients with hyperdynamic circulation resulting from acute liver failure and to ascertain whether guanylyl cyclase activation is involved in the decline of systemic vascular resistance that occurs in this pathophysiological condition, we simultaneously recorded hemodynamic data and cyclic GMP levels in patients with fulminant liver failure before and after liver transplantation and in normokinetic patients undergoing abdominal nonseptic surgery. We also compared these data with those recorded in patients with hyperkinetic shock resulting from gram-negative sepsis or nitric oxide-independent vasomotor agent (carbamate) over-dose. In all these patients we simultaneously studied kidney function, platelet counts and atrial natriuretic peptides. Patients with fulminant liver failure had higher cyclic GMP concentrations than did control patients undergoing abdominal surgery (11.02 +/- 1.55 pmol.ml-1 vs. 1.77 +/- 0.18 pmol.ml-1, p < 0.001). At similar heart-loading conditions these concentrations were lower than those in gram-negative septic shock (18.2 +/- 1.35 pmol.ml-1, p < 0.05) but higher than those in carbamate-induced shock (3.6 +/- 0.7 pmol.ml-1, p < 0.01). In addition, cyclic GMP concentrations significantly decreased from the fulminant liver failure period to the posttransplantation period, although atrial natriuretic peptide levels did not change significantly and kidney function worsened.(ABSTRACT TRUNCATED AT 250 WORDS)

[Developmental modalities of septic states. Multiple organ failure syndrome]. / Modalités évolutives des états septiques. Le syndrome de défaillance multiviscérale.

Sepsis syndrome occurs when an acute infection results in an host generalized inflammatory response including cytokines production. Death is a frequent and unpredictable sequel of this pathological condition. It may be due either to uncontrolled circulatory failure, or to multiple organ failure. With the advent of nitric oxide in the arena of the most potent vasodilatator agents, we now better understand the mechanisms of low vascular resistance during hyperkinetic septic shock. However a closer understanding of the mechanisms of multiple organ failure is actually required to improve survival rates during severe human sepsis.

Effect of okadaic acid on the cytotoxic activity of Clostridium difficile toxin B and Clostridium sordellii toxin L.

Clostridium difficile toxin B and Clostridium sordellii toxin L, which are immunologically related toxins, possess a cytotoxic activity inducing depolymerization of microfilaments and cellular retraction of cell bodies that are different for toxin B- and toxin-L-treated cells. The biological mechanisms responsible for these effects are unknown, but a previous study revealed that both toxins induce modification of phosphorylation of cellular proteins extracted from toxin B- and toxin L-treated cells without changes in protein kinase C activity or cAMP concentration. In the present study, we have investigated the effect of okadaic acid, an inhibitor of protein phosphatases, on the cytotoxic activity of toxins B and L in MacCoy cells. Firstly, we reveal by cytotoxic assay and staining of F-actin that okadaic acid (1 microM or higher) induces depolymerization of microfilaments and cellular morphological modifications which are similar to that of cells treated with toxin L. Secondly, we show that 1 microM okadaic acid potentials the cytotoxic activity of toxin L but not of toxin B. These observations suggest that the cytotoxic mechanisms induced by okadaic acid and toxin treatment are partly common, indicating that an increase in phosphorylation favors the cytotoxicity of toxin L. Since okadaic acid had no influence on the cytotoxicity of toxin B, we suggest that toxin B and L, alter the cells by different cellular biological mechanisms.

Plasma cyclic guanosine 3'-5' monophosphate concentrations and low vascular resistance in human septic shock.

OBJECTIVE: To investigate the increase in plasma cyclic GMP (cGMP) concentrations in humans with hyperkinetic septic shock (SS) and to evaluate its relationship to low systemic vascular resistance (SVR). DESIGN: Prospective clinical investigation. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 22 patients with documented SS requiring hemodynamic resuscitation, respiratory support and--in some cases--hemodialysis. MEASUREMENTS AND RESULTS: Hemodynamic data were recorded at admission time and then twice a-day during the following 72 h. We simultaneously measured cyclic GMP, atrial natriuretic peptides (ANP), creatininemia and platelet counts. At admission time, higher plasma cGMP concentrations were observed in patients with SS (11.84 +/- 1.52 pmol.ml-1) than in healthy controls (1.77 +/- 0.18 pmol.ml-1, p < 0.0001), in septicemia patients without circulatory failure (3.28 +/- 0.36 pmol.ml-1, p < 0.005) or in patients with hyperkinetic non-septic shock (3.6 +/- 0.7 pmol.ml-1, p < 0.02). In contrast, there was no significant difference between patients with SS and controls with anuria from non-septic origin. Also ANP concentrations were higher in patients with SS than in others. In addition, cGMP levels correlated negatively with SVR during the first 48 h of the study, and positively with creatininemia later when renal function worsened. However, they did not correlate significantly with ANP. CONCLUSION: These data demonstrate that a significant increase in plasma cGMP concentrations occurs during human SS and that it correlates with the decline in peripheral vascular resistance in the absence, but not in the presence, of severe renal failure. Furthermore, the increase in cGMP levels cannot be ascribed solely to enhanced ANP-induced particulate guanylyl cyclase activity. Thus, our results suggest the occurrence of another endogenous source of cGMP during hyperkinetic SS.

Tissue oxygenation during liver transplantation.

OBJECTIVES: a) To assess perioperative changes in tissue oxygenation parameters during liver transplantation; b) to evaluate the need for venovenous bypass as hemodynamic support; and c) to assess the efficacy of mixed venous oxygen saturation monitoring and the importance of lactate determinations in the management of patients following liver transplantation. DESIGN: Prospective case series. SETTING: Liver transplant unit in a university hospital. PATIENTS: A total of 68 consecutive patients undergoing liver transplantation. The entire population was analyzed before and after transplantation, dividing the patients into two groups, based on whether their initial cardiac index was higher (n = 37) or lower (n = 31) than 4.5 L/min/m2. MEASUREMENTS: Hemodynamic measurements and blood gas analyses were made before incision, before vascular clamping (including hepatic artery, portal vein and inferior vena cava), during the anhepatic phase, and at 5, 30, 60, and 120 mins following unclamping. Oxygen transport and oxygen consumption values were calculated. Serum lactate concentrations were measured by enzymatic technique. MAIN RESULTS: Mixed venous oxygen saturation was correlated with oxygen transport (Do2) in the whole population in which an abnormal oxygen consumption (Vo2)-Do2-dependent relationship occurred from the beginning of operation until 30 mins following unclamping. The comparison between hyperdynamic patients (initial cardiac index greater than 4.5 L/min/m2) with impaired tissue oxygenation and normodynamic patients showed that mixed venous oxygen saturation failed to correlate with Do2 when the cardiac index was greater than 4.5 L/min/m2 and that the Vo2-Do2 dependency was only noted in these patients. The serum lactate concentrations were similar in both groups. CONCLUSIONS: The Vo2-Do2-dependent relationship and mixed venous oxygen saturation-Do2 correlation noted in the 68 studied patients suggest the need for venovenous bypass and the reliability of mixed venous oxygen saturation monitoring in all patients scheduled for liver transplantation. However, a sharper comparison between hyperdynamic and normodynamic patients demonstrated the lack of efficacy of mixed venous oxygen saturation monitoring in predicting adequate tissue oxygenation in the first group and the mandatory need for venous shunting to limit tissue hypoxia which occurred despite its use only in these patients. Lactic acidosis appeared similarly in both groups and could not be linked to tissue hypoxia.

Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observations.

We report the hemodynamic improvements induced by intravenous methylene blue (MB), a guanylate cyclase inhibitor, in 2 patients with hyperdynamic septic shock treated with norepinephrine (NE) infusion, mechanical ventilation and hemodialysis. MB injection augmented the low vascular resistance, mean arterial pressure and induced a slight decrease of cardiac index, without any change of heart rate and pulmonary artery wedge pressure. Plasma cyclic GMP levels decreased without a significant change of atrial natriuretic factor levels. MB (2 mg.kg-1) induced a longer lasting improvement of circulatory failure without deleterious side effects, but did not prevent the occurrence of delayed multiorgan failure or subsequent death. These data suggest that in patients, severe sepsis-induced loss of vascular responsiveness to NE involves activation of soluble guanylate cyclase, possibly stimulated by enhanced nitric oxide production. Furthermore, these observations support the concept that pharmacological blockade of guanylate cyclase may improve hemodynamics but not survival rates.

Evaluation of teicoplanin for treatment of endocarditis caused by gram-positive cocci in 20 patients.

Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated for the treatment of bacterial endocarditis in an open multicenter study from May 1985 to August 1987. A total of 20 patients with positive blood culture endocarditis received teicoplanin once daily as a mean intravenous injection of 7.3 mg/kg of body weight (range, 4.8 to 10.6 mg/kg); in 17 patients, teicoplanin was combined with another antibiotic, usually an aminoglycoside. The mean duration of therapy was 28 days (range, 7 to 66 days). The diagnosis of endocarditis was confirmed by echocardiography or anatomical findings in 15 patients and established on the basis of clinical manifestations plus positive blood cultures in 5 patients. The tricuspid valve was involved in 11 of the 20 patients. Isolates from blood were 12 Staphylococcus aureus, 1 Staphylococcus hominis, 1 Micrococcus sedentarius, 1 Enterococcus faecalis, 3 Streptococcus bovis, and 2 nongroupable Streptococcus sp. At the end of therapy, bacterial eradication was achieved in 17 of 20 patients (85%), and a favorable clinical outcome had occurred in 14 of 17 evaluable patients (82%). Of these 14 patients, one relapsed 4 months after the end of treatment. Thus, teicoplanin was effective in 13 of 17 patients (76%). Mean peak levels of teicoplanin in serum were lower, 23.1 +/- 2.9 micrograms/ml, in patients who failed than in those who were cured (45.8 +/- 8.4 micrograms/ml). Side effects occurred in 7 of 20 patients (35%), and required premature discontinuation of teicoplanin in 3 patients. These side effects were fever in three patients, rash in three patients, hearing loss in two patients, and increased serum transaminase levels in two patients. This study demonstrates the efficacy of teicoplanin in the treatment of endocarditis and the need for achieving peak levels in serum close to 40 micrograms/ml. Teicoplanin should now be further evaluated in endocarditis caused by gram-positive cocci means of controlled comparative study with standard therapy.

[Acute fatty liver of pregnancy. Diagnostic value of hyperuricemia in the pre-jaundice stage]. / Un cas de stéatose hépatique aiguë gravidique. Intérêt diagnostique de l'hyperuricémie au stade pré-ictérique.

Acute fatty liver of pregnancy, with a case history where an early diagnosis could have been made, and a review of the French literature. Acute fatty liver of pregnancy, or Sheehan's syndrome is a rare but very serious complication of pregnancy. The disease is demonstrated by vomiting, abdominal pain and a high level of uric acid in the blood before jaundice is noted. Within a few days the triad of jaundice, pruritus and encephalopathy occur. These are often associated with toxaemia of pregnancy and with polyuria and polydipsia. A raised white blood count and a high level of bilirubinemia are almost always present. The outlook is very serious when haemorrhage appears. This malignant form of the disease is characterised by liver and kidney failure. Liver biopsy confirms the diagnosis. The prognosis is related to an early diagnosis and is good when labour is induced or caesarean section performed. Acute fatty liver of pregnancy is an emergency from the diagnostic as well as the therapeutic angles.

[Prognostic factors of decompensated chronic respiratory insufficiency. Apropos of a series of 272 cases]. / Facteurs pronostiques des insuffisances respiratoires chroniques décompensées. A propos d'une série de 272 observations.

Over a 6 years' period (1980-1986), 272 patients with chronic respiratory disease were admitted for respiratory failure to the same intensive care unit. The series was characterized by the high mean age of the patients (69.3 years) and by the high proportion of those who were ventilated (75%); 33.7% of the patients died within 1 month of discharge. The survival rate at 5 years estimated by the actuarial survival curve was 28%. Parameters measured during the acute decompensation phase were analyzed statistically. The main prognostic factors regarded as unfavourable were: old age and associated visceral failure particularly, important loss of weight and muscular atrophy, pre-existing neurological sequelae, left ventricular dysfunction, simplified Le Gall score above 15, presence of respiratory encephalopathy, stroke or viral infection as precipitating factors of decompensation, transfer from other hospital units after failure of medical treatment, and need for mechanical ventilation for more than 30 days.

[Vital capacity restitution curve: prognostic value in chronic decompensated respiratory insufficiency]. / La courbe de restitution de la capacité vitale: intérêt pronostique au cours des insuffisances respiratoires chroniques décompensées.

From a series of 50 patients with acute decompensation of chronic obstructive lung disease (38 of whom were treated by mechanical ventilation), the authors demonstrate the prognostic value of an easily obtained parameter of respiratory function: the vital capacity restitution curve (VCRC). From daily measurements of vital capacity, beginning on the day of admission, a graph is constructed which shows an initial period of increase in the degree of restitution, followed by stabilization of the values. An analysis of the various parameters embodied in this graph provides information about the prognosis. Such graphs can be divided into 3 zones of prognostic value: a favourable zone, an intermediate zone (mediocre survival with or without mechanical ventilation) and an unfavourable zone (death during the acute phase). Although a favourable prognosis can be made after 4 days of observation and almost always by the 10th day, an unfavourable prognosis cannot be made before the 21st day.