Clinical characteristics and outcome of 125 polymicrobial bloodstream infections in hematological patients: an 11-year epidemiologic survey.

BACKGROUND: Polymicrobial bloodstream infections (pBSI) occurring in hematological patients are still poorly understood, and specific information are very limited. OBJECTIVES AND METHODS: In this epidemiologic survey, we describe clinical characteristics and outcome of 125 consecutive pBSI occurred in oncohematological patients. Polymicrobial bloodstream infections (pBSI) were defined with the isolation of 2 or more bacteria from blood culture specimens obtained within 72 h. RESULTS: Over an 11-year period, we documented 500 bacterial bloodstream infections (BSI) in 4542 hospital admissions and 25% (125) of these were pBSI. Most common underlying hematological disease was acute myeloid leukemia and 89% of patients had severe neutropenia. Fifty pBSI (40%) occurred in patients undergoing a stem cell transplantation (SCT), mostly within 30 days from transplant (42/50-84%). Principal bacterial association was Gram-positive plus Gram-negative (57%). Resolution rate of pBSI was 82%, without differences between SCT and non-SCT cases. pBSI-related mortality was 15% (6% in SCT cases). Septic shock occurred in 16% of cases and septic shock-related mortality was 65% (75% in SCT cases and 63% in non-SCT cases; p = 0.6). Multidrug-resistant (MDR) bacteria were involved in 22% of pBSI and the MDR-pBSI-related mortality was significantly higher in SCT patients (p = 0.007). CONCLUSIONS: This observational study highlights that pBSI is not a rare bloodstream infectious complication in oncohematological patients. pBSI-related mortality is lower than 20%, but, if septic shock occurs, mortality reaches 65%. MDR bacteria were involved in 22% of cases and pBSI-MDR-related mortality was significantly higher in SCT patients.

Role of procalcitonin in predicting etiology in bacteremic patients: Report from a large single-center experience.

BACKGROUND: Procalcitonin (PCT) is routinely used for an early recognition of severe infections and for promoting appropriate use of antibiotics. However, limited data correlating values of PCT with etiology of infection has been reported. METHODS: During 2016, all positive blood cultures (BC) were retrospectively extracted in a 1100-beds Italian tertiary-care hospital. PCT and C-reactive protein (CRP) values were recorded within 24h from BC collection. Primary endpoint of the study was to investigate the correlation between PCT and CRP values and the occurrence of bloodstream infections (BSI) caused by bacteria or fungi. RESULTS: During the study period, 1296 positive BC were included: 712 (54.9%) due to Gram-positive (GP), 525 (40.5%) due to Gram-negative (GN) strains, and 59 (4.6%) caused by fungi. Among GN isolates, enterobacteriaceae were reported in 453 (86.3%) cases. PCT values were higher in patients with GN etiology (26.1±14.2ng/mL) compared to GP (6.9±4.5) and fungi (3.3±2.4). Mean values for CRP in GN, GP, and fungi were not different. Receiver Operating Characteristic (ROC) curves showed an area under curve (AUC) of 0.71 for PCT and 0.51 for CRP among GN isolates; an AUC of 0.7 for PCT and 0.52 for CRP among enterobacteriaceae. Lower AUC for PCT were reported for GP and fungi. CONCLUSIONS: PCT showed moderate performance in early detection (within 24h) of Gram-negative infections, especially those caused by enterobacteriaceae. Further prospective studies are mandatory to confirm these observations.

Management of vertebral osteomyelitis over an eight-year period: The UDIPROVE (UDIne PROtocol on VErtebral osteomyelitis).

OBJECTIVES: Vertebral osteomyelitis (VO) is a compelling clinical entity for clinicians because of its insidious and indolent course, which makes diagnosis difficult. METHODS: All patients with a suspected diagnosis of VO were analyzed over an 8-year period (January 2009 to January 2017). The UDIPROVE protocol (UDIne PROtocol on VErtebral osteomyelitis) was applied in all cases. The primary endpoint was the performance of the UDIPROVE protocol to obtain the causal bacteria of infection. RESULTS: During the study period, 133 episodes of confirmed VO were observed. The etiology of infection was obtained in 73.6% of cases: 70.5% were gram-positive, 16.3% were gram-negative, and 13.2% were mycobacteria. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed that for tubercular VO, the median standard uptake value (SUV) was higher when compared with VO caused by other bacteria. Clinical cure at the end of therapy was reported in 85.7% of patients. Previous antimicrobial therapy and a delay of more than 5 days in performing biopsy were associated with an undiagnosed etiology of VO. Targeted antibacterial therapy and follow-up with FDG-PET/CT were associated with clinical cure at the end of therapy, while the involvement of more than two vertebrae and inadequate drainage were associated with failure. CONCLUSIONS: Rigorous application of the UDIPROVE protocol allowed the causative pathogens of VO to be obtained - at about twice the rate reported in the literature. The use of FDG-PET/CT for the follow-up of infection was more reliable when compared to magnetic resonance imaging (MRI).

Serological and T Cell Responses After Varicella Zoster Virus Vaccination in HIV-Positive Patients Undergoing Renal Dialysis.

Limited data on varicella zoster virus (VZV) vaccine responses are available in HIV-positive adults, especially among those with end-stage renal disease on dialysis or undergoing kidney transplantation (KT). Serological and T cell responses were analyzed using anti-VZV IgG titers, enzyme-linked immunosorbent assay and flow cytometric intracellular cytokine staining (ICS) in two HIV-positive kidney transplant candidates undergoing dialysis and receiving VZV immunization. The results were compared with two HIV-positive and two HIV-negative VZV-seropositive patients (two kidney transplant candidates and two kidney transplant recipients), and with one HIV-negative vaccinee. HIV-positive VZV-susceptible patients received two doses of VZV vaccine 12 weeks apart. No adverse events were reported. Serological data were indicative of immunological response in one patient and corresponded to T cell responses. The second patient showed only a transient increase in anti-VZV IgG titers, but reported positive CD4+ T cell responses that were maintained after KT. Positive T cell and serological responses were detected in both HIV-positive and HIV-negative controls. VZV vaccination appeared safe and effective in HIV-positive KT candidates. VZV-specific T cell immunity was detected among transplant candidates and after KT. The assessment of VZV-specific T cell immunity using flow cytometric ICS may be more reliable compared to serology in assessing responses to VZV vaccine in this group.

Role of procalcitonin in bacteremic patients and its potential use in predicting infection etiology.

INTRODUCTION: Bloodstream infections (BSI) and their evolution to sepsis or septic shock are one of the most important causes of morbidity and mortality; for this reason, arapid recognition and diagnosis of these infections are crucial to improve patients' outcome. Area covered: Procalcitonin (PCT) is considered an important biomarker for diagnosis of infection, routinely used to identify patients developing severe bacterial infections. In this scenario, management of BSI is complicated by the increasing rate of multidrug-resistantstrains, and an early recognition of severe infections is mandatory. Moreover, an appropriate use and prescription of antibiotics is important to reduce the risk of development of further antibiotic resistances. Expert opinion: we reviewed recent literature about the use of PCT in bacteremic patients to determine its role to predict infections, severity of clinical condition and antibiotic therapy duration; its role was defined in many studies to reduce duration of antibiotic treatment, especially in critically ill patients and for lower respiratory tract infections. Moreover, we reported recent studies in which PCT showed ahigh performance to detect precociously infections due to Gram-negativestrains. Data from the literature confirm that PCT should not be used as astand-alonetest in the absence of clinical judgment.

Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation.

The objective of this study was to determine risk factors and outcomes of infections by multidrug-resistant gram-negative (MDR GN) bacteria in 241 recipients of hematopoietic stem cell transplantation (HSCT). The cumulative incidence of infections was 10.5% (95% CI, 12.0% to 25.8%), with 57% of infections occurring during the period of severe neutropenia (neutrophil count < .1 × 106/L). In multivariate analysis, allogeneic transplant and colonization with MDR GN bacteria at admission to the transplant unit were significantly associated with an increased risk of infection. Although we observed neither transplant-related mortality (TRM) nor deaths due to infections by MDR GN bacteria after autologous transplant, in the allogeneic setting a significant difference was reported in terms of overall survival (OS) and TRM between patients who developed infections and those who did not (1-year OS, 39% versus 68%; 1-year TRM, 42% versus 19%). In multivariate analysis, refractory disease and development of grades III to IV graft-versus-host disease (GVHD) were factors that affected both TRM and OS, whereas occurrence of infections by MDR GN pathogens significantly reduced OS. We conclude that eligibility to allogeneic HSCT in MDR GN bacteria carriers should be carefully evaluated together with all other factors that independently influence outcome (disease status, donor, and GVHD risk).

Clinical and therapeutic aspects of candidemia: a five year single centre study.

BACKGROUND: Candida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital. METHODS: All consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study. RESULTS: A total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P < 0.05). At multivariate analysis, steroids treatment (OR = 0.27, p = 0.005) and CVC removal (OR = 3.77, p = 0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR = 3.45, p = 0.015) and Amphothericin B lipid formulation (OR = 15.26, p = 0.033) were independently associated with higher survival probability compared with no treatment.

Post-operative shampoo effects in neurosurgical patients: a pilot experimental study.

BACKGROUND: Neurosurgical site infections are an important issue. Among the acknowledged preventive tactics, the non-shaving technique is well established in the neurosurgical setting. However, given that patient's hair around the surgical site may retain biologic material that emerges during the surgical procedure or that may simply become dirty, which may increase the risk of surgical site infections, if and when shampooing should be offered remains under debate. METHODS: A pilot experimental study was undertaken from 2011 to 2012. A series of neurosurgical patients not affected by conditions that would increase the risk of post-operative infection were assigned randomly to the exposed group (receiving shampoo 72 h after surgical procedure) or control group (receiving standard dressing surveillance without shampooing). Comfort, surgical site contamination (measured as the number of colony-forming units [CFU]), and SSIs at 30 d after surgery were the main study outcomes. RESULTS: A total of 53 patients were included: 25 (47.2%) received a shampoo after 72 h whereas 28 (52.8%) received standard care. Patients who received a shampoo reported a similar level of comfort (average=8.04; standard deviation [SD] 1.05) compared with those receiving standard care (average 7.3; SD 3.2) although this was not statistically significant (p=0.345). No statistically significant difference emerged in the occurrence of surgical site contamination between the groups, and no SSIs were detected within 30 d. CONCLUSIONS: In our pilot study, the results of which are not generalizable because of the limited sample of patients involved, a gentle shampoo offered 72 h after the surgical procedure did not increase the SSIs occurrence or the contamination of the surgical site, although it may increase the perception of comfort by patients. Further studies are strongly recommended involving a larger sample size and designed to include more diversified neurosurgical patients undergoing surgical procedures in different centers.

Current antibiotic management of prosthetic joint infections in Italy: the 'Udine strategy'.

The rate of prosthetic joint infections followed and cured at our institution is constantly increasing, in line with epidemiological data from the recent literature. This is probably related to the greater number of knee and hip prostheses implanted every year. For intermediate and late infections, only the two-stage approach is applied, as this demonstrates the best outcome in our experience. Particular attention is paid to microbiological isolation of the pathogen: multiple samples of tissue are collected during the interventions, and kept in culture for a longer period of time than usual. Sonication of prosthetic devices is used to enhance the sensitivity and specificity of the microbiological cultures. Histological examination influences surgical choices either towards implantation of a new prosthesis or replacement of the spacer. An empirical antibiotic backbone of a glycopeptide/lipopeptide and rifampicin is chosen, due to the leading role of Gram-positive bacteria in this setting and the high incidence of methicillin resistance in our centre (>30%), followed by an antibiotic regimen containing linezolid. If specific risk factors are present, an anti-Gram-negative drug is added to the regimen. Duration of therapy depends upon the approach that is chosen, usually being 6 weeks when the prosthesis is removed. Despite at the moment being limited by its small sample size, data from our experience confirms that our empirical approach may represent a valid choice during the early phase of treatment, by keeping linezolid for a step-down therapy of shorter duration (4 weeks).

Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain.

Candidemia has become an important bloodstream infection that is frequently associated with high rates of mortality and morbidity, and its growing incidence is related to complex medical and surgical procedures. We conducted a multicenter study in five tertiary care teaching hospitals in Italy and Spain and evaluated the epidemiology, species distribution, antifungal susceptibilities, and outcomes of candidemia episodes. In the period of 2008 to 2010, 995 episodes of candidemia were identified in these hospitals. The overall incidence of candidemia was 1.55 cases per 1,000 admissions and remained stable during the 3-year analysis. Candida albicans was the leading agent of infection (58.4%), followed by Candida parapsilosis complex (19.5%), Candida tropicalis (9.3%), and Candida glabrata (8.3%). The majority of the candidemia episodes were found in the internal medicine department (49.6%), followed by the surgical ward, the intensive care unit (ICU), and the hemato-oncology ward. Out of 955 patients who were eligible for evaluation, 381 (39.9%) died within 30 days from the onset of candidemia. Important differences in the 30-day mortality rates were noted between institutions: the lowest mortality rate was in the Barcelona hospital, and the highest rate was in the Udine hospital (33.6% versus 51%, respectively; P = 0.0005). Overall, 5.1% of the 955 isolates tested were resistant or susceptible dose dependent (SDD) to fluconazole, with minor differences between the hospitals in Italy and Spain (5.7% versus 3.5%, respectively; P = 0.2). Higher MICs for caspofungin were found, especially with C. parapsilosis complex (MIC90, 1 µg/ml). Amphotericin B had the lowest MICs. This report shows that candidemia is a significant source of morbidity in Europe, causing a substantial burden of disease and mortality.