Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections.

The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.

Epidemiology of nosocomial infection in 125 Italian intensive care units.

AIM: A continuous infection surveillance program was conducted by GiViTI throughout 2006 in Intensive Care Units (ICUs). METHODS: This was a prospective epidemiological study carried out in 125 Italian intensive care units. All patients have been included in the study. Aside from the detailed clinical information collected for all patients, in cases of infection upon ICU admission and for the first site-specific episode that occurred during the patient's stay, the following data were collected: severity upon admission, micro-organisms and their antibiotic resistance patterns, subsequent multiple episodes in the same site, origin of infections and maximum severity reached. The diagnostic criteria for all infections are explicitly stated. RESULTS: A total of 34,472 patients entered the study. Infection upon admission was present in 12.6% of patients, with a high level of ICU and hospital mortality (29.4% and 38.7%, respectively). In 3148 patients one or more infections were reported as ICU-acquired with an overall incidence of 9.1% and an ICU and hospital mortality of 27.2% and 35.1%, respectively. Out of the device-related infections, ventilator-associated pneumonia was the most frequently diagnosed (8.9/1000 days on ventilator). Catheter-related blood stream infection was reported with a low incidence (1.9/1000 central venous catheter days). Nearly 20% of more than 5000 isolated microorganisms were classified as multi-drug resistant, with methicillin-resistant Staphylococcus aureus as the most frequently reported bug. CONCLUSIONS: The ad hoc expanded GiViTI software "Margherita2" allows continuous infection surveillance in Italian ICUs, annually providing an extensive and updated database. Interventions to improve infection prevention and patient safety should be tailored to accommodate these data.

Linezolid treatment for gram-positive infections: a retrospective comparison with teicoplanin.

In randomized studies linezolid, indicated for Gram-positive infections, was as effective as teicoplanin in critical ill patients or was superior to teicoplanin in skin infection, pneumonia and bacteremia. We performed a 2-year comparative, retrospective study of patients treated with linezolid or teicoplanin in a single hospital for the same indications. We collected information about the type of infection, the responsible pathogen, therapy administered before study drugs, antibiotic associated with the study drugs, length of hospital stay (LOS), adverse events and outcome of the infections. The aim of the study was to evaluate the efficacy of linezolid in this retrospective patients series. Overall we identified 169 patients treated with linezolid and 91 with teicoplanin. Response to therapy, (resolution or improvement of infection) was better in patients treated with linezolid compared to teicoplanin (83.9% versus 69.2%, p=0.002). Response to therapy by type of pathogen showed the superior efficacy of linezolid against Staphylococcus aureus (including MRSA) and enterococci; although not statistically significant because of the small number of patients enrolled, they were close to significance (p<0.056 for S. aureus, p<0.055 for MRSA, p<0.061 for enterococci). Overall LOS in linezolid-treated patients was 4.6 days (p<0.041) less. Empirical use of linezolid reduced lOS by 6 days (p<0.038), especially in VAP and bacteremia patients (p<0.05). Mortality due to infection was 9.8% in both groups, and adverse events were most frequently documented in linezolid-treated patients. Linezolid was clinically superior to teicoplanin in the treatment of Gram-positive infections.

Can routine surveillance samples from tracheal aspirate predict bacterial flora in cases of ventilator-associated pneumonia?

AIM: The aim of this study was to investigate the hypothesis that periodical sampling of the tracheo-bronchial tree in the absence of clinical suspicion of pneumonia is useful to identify bacteria responsible for subsequent late ventilator associated pneumonia (VAP). This was a retrospective observational human study carried out in two medical-surgical intensive care units of two different hospitals. From January 1999 to December 2000, 559 patients, who received invasive respiratory support for more than 48 hours, were screened. METHODS: Tracheal aspiration (TA) was performed once or twice weekly in all mechanically ventilated patients. The microbiological findings from TA surveillance cultures done in the eight days before suspicion of VAP were compared to those isolated from the positive diagnostic samples done for late onset VAP (after more than four days of mechanical ventilation). The sensitivity, specificity, and positive/negative predictive values of the ability of the surveillance sample to anticipate the VAP pathogen were calculated. RESULTS: Among the microorganisms isolated from TA, 68% were retrieved from diagnostic samples. All VAP pathogens previously isolated were from 43% of the TA samples. If TA was collected 2-4 days before the clinical diagnosis of VAP, pathogens were detected in 58% of samples. In contrast, only 27% were collected more than four days earlier (P<0.05). The positive predictive values for Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus from routine TA samples were 92% and 90%, respectively. The negative predictive values for Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus from routine TA samples were 75% and 89%, respectively. CONCLUSIONS: TA cultures in ventilated patients may help to predict pathogens. Early detection may lead to earlier treatment in long term ventilated patients when VAP is suspected.

Burnout in intensive care unit.

AIM: The aim of this paper was to study in intensive care unit (ICU) the impact of variable ''professional role'' and ''gender'' on the defence mechanisms, on the troubles of mood and on the markers of the burnout syndrome, and to study the correlation between specific defence mechanisms or specific troubles of mood and the onset of burnout syndrome. METHODS: An observational study by administration of psychometric tests was carried out. Twenty-five nurses and 25 doctors working in two differents ICU of the Azienda Ospedaliera-Universitaria Pisana were enrolled. Three psychometric tests concerning the defence mechanisms (Defense Mechanism Inventory), the troubles of mood (Profile of Moods States) and the burnout syndrome (Maslach Burnout Inventory) were administered and the three tests were analysed to study the features of each person enrolled. RESULTS: The study shows the presence within doctors of two dimensions of burnout syndrome (emotional exhaustion in women and depersonalization in men) much greater than nurses. The doctors show the presence of defence mechanism as overturning, aggressiveness and rationalization, and troubles of mood as depression-despondency and aggressiveness-anger. Compared to men, women show turning to one self as defence mechanisms, whereas the men show aggressiveness-anger as trouble of mood. The women doctors show depression-disheartement as trouble of mood, the men doctors show tension-anxiety. We showed a correlation between tiredness-indolence, depression-disheartement and onset of emotional exhaustion, as a correlation between aggressiveness, aggressiveness-anger in man and oncet of depersonalization. Finally we correlated the absence of tension-anxiety as trouble of mood and overturning as defence mechanism with a good personal accomplishment at work. CONCLUSION: The burnout syndrome is present in health-care workers in ICU and it is significantly affected by operating role and gender. We must be aware of this phenomenon in order to study it and to reduce it.

Linezolid cerebrospinal fluid concentration in central nervous system infection.

We report two cases of central nervous system infection due to methicillin-resistant Staphylococcus epidermidis treated with linezolid. The first case was a 72-year old woman with ventriculitis in the presence of intraventricular catheter: therapeutic effectiveness was documented clinically and microbiologically; serum and cerebrospinal fluid levels were measured after the first and fourth doses: trough linezolid concentrations in cerebrospinal fluid were 1.44 and 2.9 mg/L respectively, higher than the minimum inhibitory concentration (MIC). The second case was a 27-year old man with post-traumatic cerebral abscess; during 5 days linezolid was not found in his cerebrospinal fluid despite very high serum level peak, and the drug was not detectable in cerebral tissue surgically removed after 14 days of therapy. Linezolid may not reach therapeutic concentrations in cerebrospinal fluid, and, when possible, we suggest that drug levels be monitored.

[Infection surveillance in intensive care units. Preliminary results of a multicenter GiViTI study in 71 Italian ICUs]. / La sorveglianza delle infezioni in terapia intensiva. Risultati preliminari di uno studio multicentrico GiViTI su 71 TI.

AIM: Infection surveillance and control in ICU is believed to be a means to improve the quality of assistance. The importance of this activity is supported by both epidemiological (rate and severity of infection in ICU) and economic (efficiency, cost-benefit and cost-effectiveness analysis) evaluations. Many authors thinks that infection surveillance and control should be performed with a routine tool in order to obtain remarkable data without too much time loss, and used by many ICUs, in order to compare the data. METHODS: A prospective observational study in 71 Italian ICUs participating in GiViTi. All patients admitted in each ICU during 6 month (except those discharged alive within 48 hours from admission) were enrolled and surveyed. Demographic and clinical data, data relating to nosocomial and at admission infections, risk factors, responsible micro-organisms, antibiotics use and outcome were collected. RESULTS: A total of 5814 patients (98% of eligible patients) were surveyed. The overall incidence of infected patients was 43%. The incidence of patients with nosocomial infection was 18% (1062 patients). Pneumonia, bacteraemia and urinary tract were the main sites. The major isolated micro-organism responsible of infection were staphylococcus (29.7%) and pseudomonas (16.2). Only 17% of all patients was not treated with antibiotics, and 72% of patients without infection was treated with antibiotics. CONCLUSION: These preliminary data confirm the importance of infection in ICU and the need of continuous surveillance. We propose a tool that can be useful for continuous and multicentric infection surveillance in ICU.

Evaluation of a standardized protocol of intracavitary recombinant interferon alpha-2b in the palliative treatment of malignant peritoneal effusions. A prospective pilot study.

OBJECTIVE: Several schedules with variable doses of intracavitary interferon have been proposed for the management of metastatic peritoneal effusions. This prospective pilot study evaluated the efficacy of a standardized schedule of intraperitoneal interferon alpha(2b). METHODS: In 41 cancer patients with malignant ascites a 9-french intraperitoneal catheter was placed under sonographic guidance, and ascites was drained until abdominal ultrasound showed complete absence of effusion. Interferon alpha(2b), 6 or 9 million units (body weight 50 kg, respectively), was then administered via the tube, which was clamped for 6 h. 6 courses were given at 4-day intervals. In comparison with pretreatment levels, the 30-day response was classified as complete (CR) = no fluid recurrence, partial (PR) = fluid recurrence <50% and no response (NR) = >50%. Responders were monitored until fluid recurrence requiring paracentesis. RESULTS: 12 patients had CR, 15 PR, 14 NR. Global response (GR) was 65.9%. In ovarian cancer, GR was 75% and was not influenced by the quantity of the pretreatment daily fluid production. In the other cancers, a pretreatment fluid production

[Antibiotic therapy in Italy. Current data and proposals for the future]. / Terapia antibiotica in Italia. Dati attuali e proposte per il futuro.

Data concerning antibiotic therapy in italian ICUs are presented. These data were not directly measured: they have been derived from a previous study on costs of intensive care treatments. 78% of 1065 patients received antibiotic therapy. Empirical therapy was started in 82% of septic patients. 93% of septic patients had at least one antibiogram. In 96% of cases, 2 or more antibiotics were given. 85% of surgical non septic patients received antibiotic prophylaxis for an average of 3.6 days, with a 3rd generation cephalosporin in the majority of cases. 60% of medical non septic patients received antibiotic prophylaxis for an average of 6.2 days, mostly with a 3rd generation cephalosporin. These data raise doubts about the proper use of prophylaxis. These data can be considered a useful starting point for the development of a program of surveillance of infections in Italian ICUs.

[Pinch-off syndrome and rupture of totally implanted venous access. Report of a case]. / Sindrome del "pinch off" e rottura di accesso venoso totalmente impiantato. Descrizione di un caso.

Permanently implanted central venous catheters (CVC) are very frequently used in the management of patients with cancer for the administration of chemotherapy, for infusing intravenous therapy or for total parenteral nutrition. Common complications in the use of CVC include venous thrombosis, infection, extrusion and occlusion. A potentially serious complication of implantable subclavian venous access devices is the "pinch-off" syndrome: the mechanical compression between the clavicle and first rib. The next stage of complication is catheter fracture, which is sometimes complicated with embolization. Repeated trauma to the catheter with mechanical compression between the clavicle and first rib has been postulated as the cause of fracture. Prompt retrieval should be attempted in all cases to prevent further complications. We reported a case.

Intravenous itasetron: establishing the effective dose range for the prophylactic control of acute emesis in cancer patients undergoing high-dose cisplatin chemotherapy.

Nausea and vomiting induced by chemotherapy are a major cause of distress to patients and reduce compliance with potentially beneficial treatment. Itasetron hydrochloride is a new 5-hydroxytryptamine3 (5-HT3) antagonist with potent antiemetic properties. It is more potent than ondansetron in animal models and in early clinical studies it demonstrates a long half-life and does not undergo hepatic biotransformation before elimination. The aim of this open, uncontrolled study was to establish the effective dose range of itasetron hydrochloride given intravenously (i.v.) to patients due to receive high-dose cisplatin chemotherapy (50-120 mg/m2) for the first time. Thirty-nine patients were enrolled in the trial and received a single i.v. infusion of itasetron hydrochloride at a dose of 17-280 microg/kg body weight before commencing the cisplatin infusion (median dose 90-110 mg/m2). Antiemetic protection was demonstrated by doses in the range of 35-280 microg/kg. The 17 microg/kg dose was not effective. Treatment failure (>5 emetic episodes/24 hours) was reported in only six (16%) of the 38 evaluable patients over all treatment groups. Adverse events were generally mild or moderate and of a similar type and incidence to those of current 5-HT3 antagonists. Physicians' and patients' assessments of efficacy and tolerability of itasetron hydrochloride were similar, the majority rating the treatment as 'good' or 'very good'. In conclusion, itasetron hydrochloride is effective in the dose range 35-280 microg/kg in preventing cisplatin-induced emesis. Taken together with results from a larger dose-finding study, a dose corresponding to 35 microg/kg (equivalent to 2.5 mg itasetron, calculated as free base) has been pursued in Phase III studies with the i.v. formulation.

Energy expenditure and severity of injury and illness indices in multiple trauma patients.

OBJECTIVE: To determine whether the energy expenditure of mechanically ventilated multiple trauma patients correlates with the severity of injury and illness indices before important systemic infection has complicated the clinical course, and to compare the energy expenditure with the energy expenditure expected from the Harris-Benedict equation adjusted with correction factors for trauma. DESIGN: Prospective, clinical study. SETTING: General intensive care unit of a university teaching hospital. PATIENTS: Immediate multiple trauma adult patients who required mechanical ventilation. INTERVENTIONS: Metabolic cart connected to the ventilator. MEASUREMENTS AND MAIN RESULTS: Data on admission to the emergency department and during the first 24 hrs of intensive care unit admission were collected for computation of severity of injury and illness indices, respectively. Resting and total energy expenditures were derived at least 48 hrs after intensive care unit admission by continuous indirect calorimetry. Predicted basal energy expenditure was obtained using the Harris-Benedict equation and predicted total energy expenditure was calculated using the Harris-Benedict value adjusted with correction factors for trauma. Twenty-six multiple trauma adult patients completed the study. No statistically significant correlations were observed between both the resting energy expenditure and the total energy expenditure and the Injury Severity Score, Revised Trauma Score, Simplified Acute Physiologic Score II, Acute Physiology and Chronic Health Evaluation II score, and Glasgow Coma Scale score. A regression model of total energy expenditure was developed with the following variables: Harris-Benedict equation, heart rate, and minute ventilation (p = .01; r2 = .74). The resting energy expenditure/predicted basal energy expenditure ratio was 1.17+/-0.2 and the total energy expenditure/predicted total energy expenditure ratio was 0.76+/-0.1. CONCLUSIONS: In mechanically ventilated multiple trauma patients the energy expenditure is not correlated to the severity of injury and illness indices but is dependent on the Harris-Benedict equation in addition to heart rate and minute ventilation. Furthermore, this patient population is characterized by a moderate state of hypermetabolism, and the Harris-Benedict prediction modified with correction factors for trauma systematically overestimates the total energy expenditure.

High-dose folinic acid and 5-fluorouracil alone or combined with hydroxyurea in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research.

Patients with histologically confirmed advanced colorectal cancer were randomized to receive folinic acid (FA; 500 mg/mq in 2-hour intravenous infusion) and 5-fluorouracil (5FU; 600 mg/mq given as an intravenous bolus 1 hour after FA), beginning every week for 6 weeks, followed by a 2-week rest period, either without hydroxyurea (HU, arm A) or with HU (35 mg/kg per day) given orally in three administrations (every 8 hours) starting 6 hours after 5FU administration (arm B). Six weekly doses were considered one course. One hundred eighty-two patients were randomized in this trial and 162 (89%) were evaluable for response: 81 patients in arm A and 81 patients in arm B. Objective response was observed in 18 (one complete response and 17 partial responses) of 81 evaluable patients (22%; 95% confidence interval, 13-31%) in arm A, and 24 (nine complete responses and 15 partial responses) of 81 patients (30%; 95% confidence interval, 20-40%) in arm B. There was no difference in terms of median time to progression and median survival. Gastrointestinal toxicity was the most frequently observed toxicity in both arms. The double modulation of 5FU, FA plus HU does not appear to be better than the classic 5FU plus FA schedule. This trial confirms that 5FU and FA reached a plateau of 20% to 30%.

Depression, psychosocial variables and occurrence of life events among patients with cancer.

Depressive disorders and psychosocial related factors were investigated in 113 patients one year after the diagnosis of cancer. Patients with an ICD-10 diagnosis of depression (31% of the sample) showed higher external locus of control, poorer social support, higher incidence of undesirable and/or uncontrollable events than non-depressed patients. They also differed in reporting more frequently a life-time history of emotional disorders, inability to adjust to the diagnosis of cancer and in having a lower score on the performance status. Of these factors, past psychiatric history, early maladjustment to cancer, poor social support and low performance status were predictors of depressive symptoms. However, because of the cross-sectional nature of the study, no conclusion regarding a causal relationship between depression and psychosocial variables is possible.

Response of brain metastases from lung cancer to systemic chemotherapy with carboplatin and etoposide.

30 consecutive patients suffering from cerebral metastases from lung cancer [12 small cell lung cancer (SCLC), 18 non-small cell lung cancer (NSCLC)] were given systemic chemotherapy with carboplatin (300 mg/m2/day 1 every 4 weeks) associated with etoposide (120 mg/m2 days 1-3 every 4 weeks). 21 patient were untreated; 9 patients had had previous chemotherapy, 8 with platinum derivatives. Altogether 98 cycles of chemotherapy were administered. The results were as follows: 3 complete response (3 SCLC; 10%), 7 partial response (4 SCLC, 3 NSCLC; 23.3%), 5 stable disease (1 SCLC, 4 NSCLC; 16.7%), 15 progressive disease (4 SCLC, 11 NSCLC; 50%). The overall response was 33.3%. Of the 10 patients who responded to treatment, 4 had had previous chemotherapy with platinum derivatives. Treatment was generally well tolerated; 5 patients experienced grade 4 bone marrow toxicity; in 4 treatment was suspended because of progression, and 1 patient died after the 4th cycle due to pneumonia with bone marrow aplasia. Mean survival of patients responsive to treatment was 38.6 weeks (range 15-99); overall survival was 24.8 weeks (range 2-99), in SCLC 23 weeks (range 6-52) and in NSCLC 29.8 weeks (range 2-99). The combination of carboplatin and etoposide is highly successful in the treatment of cerebral metastases from lung cancer and it could be a valid alternative to the traditional radiotherapy.

Henoch-Schönlein syndrome associated with breast cancer. A case report.

The association of the Henoch-Schönlein syndrome with leukemias and lymphomas, though rare, is well known, but this type of pathology appears to be exceptional in the case of solid tumors. The authors report a case of malignant breast tumor wherein cutaneous vasculitis appeared at the moment of the disease's progression.