Quantification of 1,3-ß-d-glucan by Wako ß-glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study.

OBJECTIVES: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available ß-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. METHODS: BDG results by Wako ß-glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. RESULTS: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1-3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut-offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively). CONCLUSIONS: The classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae.

Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking. Methods: We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results: The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.

Pulmonary complications in patients receiving a solid-organ transplant.

PURPOSE OF REVIEW: Major improvements in perioperative care and immunobiology have not abated the risk for severe pulmonary complications after solid-organ transplantation. The aim of this study is to update information on infectious and noninfectious pulmonary complications after solid-organ transplantation, addressing epidemiology, risk factors, diagnostic workup, and management. RECENT FINDINGS: Infectious and noninfectious postoperative pulmonary complications depend on the grafted organ and the anatomical site of transplantation. Kidney transplants have the lowest incidence of pulmonary complications, the highest being reported for heart, lung, and liver recipients. Respiratory tract infections, ranking first in heart and lung transplants and second in liver recipients, are a common cause of mortality. Risk factors include end-stage organ disease, comorbidities, perioperative procedures, and graft function. Factors specific for infections are timeline, state of immunosuppression, and graft dysfunction. Nosocomial multi-drug resistant pathogens are frequently responsible for the most severe infections. Aggressive diagnostic workup, early and broad empiric antiinfective therapy, and deescalation policy are the mainstays of their management. The role of intraoperative protective ventilation is under scrutiny. SUMMARY: Pulmonary complications after solid-organ transplantation, and particularly infections, are able to compromise the extremely good results of the transplant procedures. Solid-organ transplantation recipients challenge the ICU physician with unique aspects of their post-transplant course, adding, in an already critical patient, the immunosuppressed state and the quality of the functional recovery of the graft.

Transjugular intrahepatic portosystemic shunt (TIPS): the anesthesiological point of view after 150 procedures managed under total intravenous anesthesia.

TIPS is a percutaneous procedure which diverts blood from the portal to the systemic circulation preventing rebleeding from varices and stopping or reducing the formation of ascites. The choice of the anaesthetic technique is still a matter of debate. Since January 2003, 150 consecutive TIPS were performed using total intravenous anesthesia (TIVA), (propofol/fentanyl or remifentanil), endotracheal intubation and mechanical ventilation. Sixty-one patients were classified as ASA 2, 73 ASA 3, and 16 ASA 4. According to CHILD classification, 96 patients were in Class A, 48 in Class B, 6 in Class C. Mean duration f the procedure was 100+/-62 min. After TIPS placement Portal vein pressure decreased from 30+/-10 to 14+/-4 mmHg while RAP increased from 8+/-4 to 12+/-6 mmHg. Intraoperative fluid management included mainly crystalloids (750+/-200 ml, 5.4+/-1.5 ml/kg/h). Fresh frozen plasma (median 2 units, range 1-3) was given in 20 patients (13%) if PT INR was >2. Packed red cells (median 2 units, range 1-5) were transfused in 35 patients (23%) to keep haematocrit >25%; platelets were administered before the procedure if platelet count was <50,000x10(-9) (20 patients, 13%). Urine output was kept above 4 ml/kg/h with loops diuretics (mean diuresis 700+/-200 ml, 5+/-1.5 ml/kg/h). Ten patients (6.6%) required ICU after the procedure, because of intraoperative hemodynamic instability. Three patients (2%) died in the early postoperative period because of multiple organ failure associated with the acute deterioration of an already marginal hepatic function.

Prospective monocentric study of non-tunnelled central venous catheter-related complications in hematological patients.

Indwelling central venous catheters (CVCs) are used in the management of hematologic patients. However, insertion and maintenance of CVCs are susceptible to complications. Study design and methods data concerning 388 consecutive catheterisations, performed in oncohematologic patients between April 2003 and December 2004, were prospectively collected. At insertion thrombocytopenia was present in 109 cases (28.1%) and neutropenia in 67 (17.3%). Hemorrhage after CVC insertion occurred in five thrombocytopenic patients (1.3%). The median duration of catheterisation was 18.8 days (range 1-89), longer in the 7-French CVCs utilised in leukemic patients (24.3 days) and shorter in 12-French CVCs (11 days), used for PBSC harvesting. Deep venous thrombosis was diagnosed in 13 cases (3.3%). Ninety-two catheterisations (12.6/1000 days-catheter) were complicated by infections: 19 local infections (4.8%) and 73 (18.8%) bacteraemias of which 45 (11.6%) were catheter-related, mainly due to Gram positive germs (32/45, 71.1%). The frequency of catheter-related bacteraemia was 7.2 events/1000 days-catheter. Thirteen CVCs were removed due to thrombosis, 15 due to infections, 20 due to malfunction, the remaining 333 at patients discharge. At univariate analysis high-dose chemotherapy (p = 0.013), 7-Fr lumen (p = 0.023), acute myeloid leukemia (AML) (p = 0.001), duration of neutropenia >10 days and length of catheterisation were significantly correlated to infection. Multivariate analysis confirmed the duration of catheterisation, AML and high-dose chemotherapy as risk factors. Even though hematological in-patients are at increased risk for bleeding and infections, non-tunnelled CVCs offer a safe venous access also in patients affected by severe thrombocytopenia and prolonged neutropenia.