Putative invasive pulmonary aspergillosis within medical wards and intensive care units: a 4-year retrospective, observational, single-centre study.

Blot and colleagues have proposed putative invasive pulmonary aspergillosis (PIPA) definitions for troublesome diagnosis in suspected patients outside the classical criteria of immunosuppression. We retrospectively included in the study all admitted patients with an Aspergillus spp. positive culture within lower airway samples. Overall, Aspergillus spp. positivity in respiratory samples was 0.97 every 1000 hospital admissions (HA): 4.94 and 0.28/1000/HA, respectively, in intensive care units (ICUs) and medical wards (MW). 66.6% fulfilled PIPA criteria, and 33.4% were defined as colonized. 69.2% of PIPA diagnosis occurred in the ICU. Antifungal therapy was appropriate in 88.5% of subjects with PIPA and 37.5% of colonized, confirming the comparison between deads and lives. Patients with PIPA in the ICUs had more frequent COPD, sepsis or septic shock, acute kidney injury (AKI), needed more surgery, mechanical ventilation (MV), vasopressors, hemodialysis, blood or platelets transfusions. PIPA in MW had associated with a history of smoking, interstitial lung disease and inhaled steroid therapy. Overall mortality within 21 days was 50%: 54.2% in ICU, 36,8% in MW. Factors associated with death were length of hospitalization, influenza, pneumonia, liver transplant, AKI, ARDS, sepsis and septic shock. PIPA in the ICU had higher disease severity and needed more organ support than MW cases, despite that cases of PIPA in MW are emerging with trends difficult to demonstrate given the problematic diagnosis.

Epidemiology and risk factors for mortality in bloodstream infection by CP-Kp, ESBL-E, Candida and CDI: A single center retrospective study.

BACKGROUND: The incidence of C. difficile infection (CDI) and of bloodstream infection (BSI) caused by Candida spp., ESBL-E-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing K. pneumoniae (CP-Kp) is associated with high mortality. METHODS: We conducted a single centre retrospective study on patients admitted to Molinette Hospital, Turin, Italy, from January 2013 to April 2015 with CDI or BSI caused by Candida, ESBL-E or CP-Kp. For each patient demographic, clinical and microbiological data were collected. Aims of this study were to describe epidemiology and to evaluate risk factors for in-hospital mortality in this group of patients. RESULTS: Seven hundred-eighty six cases were analyzed: 398 CDI, 137 candidemia, 125 ESBL-E BSI and 126 CP-Kp BSI. CDI, candidemia and ESBL-E BSI were more frequently reported in internal medicine wards (IMW), whilst CP-Kp were more described in intensive care unit (ICU). Sixty-six percent of patients had a previous hospitalization and the majority of patients had several medical comorbidities. In-hospital death occurred in 23.4%. Independent risk factors for mortality were antibiotic therapy before hospital admission, cardiovascular diseases, neutropenia, urinary catheter, total parenteral nutrition, SIRS and higher creatinine levels at diagnosis. Previous abdominal surgery, inflammatory bowel disease, higher serum albumin levels at the admission and fever at diagnosis were significantly associated with survival. CONCLUSION: Our data showed that CDI, ESBL-E BSI and candidemia are more frequent in frail patients, admitted to IMW, with chronic comorbidities and broad exposure to antibiotic therapies, with the exception for CP-Kp BSI, still more common in the ICU.

Current use and potential role of procalcitonin in the diagnostic work up and follow up of febrile neutropenia in hematological patients.

INTRODUCTION: Febrile neutropenia (FN) represents a life-threatening complication in hematological malignancies. Its etiology is most often due to infections even though FN of other origins, such as tumor-related fever and non-infectious inflammation, should rapidly be ruled out. Initially, C-reactive protein and, more recently, procalcitonin (PCT) have been proposed as useful biomarkers for differential diagnosis. PCT was shown to be a good biomarker of bacterial infections and their clinical outcomes. Definition of standard cut-offs and design of PCT-guided treatment protocols remain however to be defined. Areas covered: In this review, highlights on the current clinical use of PCT and its potential role as a diagnostic tool have been discussed by a panel of physicians from different areas of expertise. We provide current clinical evidence that PCT has been shown to be a reliable biomarker to differentiate fever of bacterial origin from other causes. Moreover, the Authors convened to a round-table to discuss their 'real-life experience' and offer their recommendations by a Delphi survey. Expert commentary: PCT has an important clinical role in FN. Issues such as the validation of a specific decision algorithm that includes PCT to monitor antibiotic choice and treatment duration will be addressed in prospective studies.

Management of carbapenem-resistant K. pneumoniae in allogenic stem cell transplant recipients: the Turin bundle.

Carbapenem resistance has evolved rapidly since 2001 and the distribution of Carbapenemase-producing Klebsiella pneumoniae (CR-Kp) is currently a public health concern worldwide. In the haematological setting, especially in allogenic transplant, CR-KP infections were associated with a mortality up to 65%. Aim of this report is to describe the management of patients colonized by CR-Kp and undergoing allo- HSCT with a multiple-step intervention strategy: the "Turin bundle". Steps included oral gentamicin (GO) within 20 days before allo-HSCT, avoidance of levofloxacin prophylaxis during neutropenia, treatment of febrile neutropenia with tigecycline 100 mg bid and piperacillin-tazobactam at standard dosages and early appropriate combination therapy for patients with severe sepsis. In our small series all patients survived, no resistance to oral gentamicin was observed and 60% of patients had negative rectal swabs after transplant.

Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study.

PURPOSE: The aim of the study was to describe the characteristics of cirrhotic patients with candidemia and intra-abdominal candidiasis (IAC) and to evaluate the risk factors associated with 30-day mortality. METHODS: A multicenter multinational retrospective study including all consecutive episodes of candidemia and IAC in adult patients with liver cirrhosis in 14 European hospitals during the period 2011-2013 was performed. RESULTS: A total of 241 episodes (169 candidemia, 72 IAC) were included. Most Candida infections were acquired in hospital (208, 86.3%), mainly in the intensive care unit (ICU) (121, 50.2%). At clinical presentation, fever was seen in 60.6% of episodes (146/241) and septic shock in 34.9% (84/241). C. albicans was the most common species (found in 131 episodes, 54.4%), followed by C. glabrata (35, 14.5%) and C. parapsilosis (34, 14.1%). Overall, the 30-day mortality was 35.3%. Multivariable analysis identified candidemia (OR 2.2, 95% CI 1.2-4.5) and septic shock (OR 3.2, 95% CI 1.7-6) as independent factors associated with 30-day mortality. Adequate antifungal treatment (OR 0.4, 95% CI 0.3-0.9) was associated with survival benefit. CONCLUSIONS: A shift towards increasing prevalence of C. glabrata and C. parapsilosis species in patients with liver disease was documented. Candidemia and IAC were associated with significant mortality in cirrhotic patients. Thirty-day mortality was associated with candidemia and severe clinical presentation, whereas adequate antifungal treatment improved the prognosis.

Candidemia, and infections by Clostridium difficile and carbapenemase-producing Enterobacteriaceae: new enteropathogenetic opportunistic syndromes?

In this paper we analyze three enteropathogenetic opportunistic infections represented by Candida spp., C. difficile and carbapenemase-producing K. pneumoniae. The common pathogenetic pathway is based on an alteration of the intestinal flora, now mainly referred as the human microbiome, with secondary opportunism for infections caused by Candida, C. difficile and carbapenemase-producing Enterobacteriaceae ("CCC"). We highlight the epidemiology, risk factors, clinical syndromes associated with the pathogens and we propose some new issues related to the epidemiology and diagnosis of candidemia, also using hierarchical cluster analysis, definitions of levels of interventions in patients colonized or infected by carbapenemase-producing bacteria. The "enteropathogenetic" opportunistic syndromes are best prevented with antimicrobial stewardship programs aiming at increasing diagnostic specificity of infectious syndromes to reduce the antimicrobial use and costs. Appropriate guidelines for infection control should also be implemented to reduce the nosocomial spread of enteropathogenetic microbes.

The Effect on mortality of fluconazole or echinocandins treatment in candidemia in internal medicine wards [corrected].

The incidence of candidemia has increased over the past two decades, with an increased number of cases in Internal Medicine and a prevalence ranging from 24% to 57%. This single-center retrospective study was performed to evaluate the epidemiology and the risk factors associated with mortality of candidemia in patients admitted to Internal Medicine wards (IMWs) of the City of Health and Sciences, Molinette Hospital, Turin, from January 2004 to December 2012. For each patient, demographic, clinical and microbiological data were collected. A case of candidemia was defined as a patient with at least one blood culture positive for Candida spp. Amongst 670 episodes of candidemia, 274 (41%) episodes occurred in IMWs. The mortality was 39% and was associated at multivariate analysis with sepsis, cirrhosis and neurologic diseases, whilst removal of central venous catheter ≤48h was significantly associated with survival. In the 77 patients treated with early antifungal therapy the mortality was 29% and was not significantly different with caspofungin or fluconazole, whilst in patients with definitive therapy the mortality was significantly lower with echinocandins compared to fluconazole (11.7% Vs. 39%; p=0.0289), a finding confirmed by multivariate analysis. The mortality was significantly associated with sepsis, cirrhosis and neurologic diseases, whilst CVC removal ≤48h was associated with survival. In patients with early therapy, fluconazole or caspofungin were equally effective. However, echinocandins were significantly more effective as definitive treatment, a finding not explained by differences in treatment delays. Further studies are needed to understand the full potential of these different therapeutic strategies in IMWs.

Cytomegalovirus central nervous system compartmentalization in a patient presenting with AIDS.

Cytomegalovirus (CMV) central nervous system involvement is uncommon and hardly diagnosed because it can mimic many different conditions. We here present a case of an HIV-positive patient with neurological signs and symptoms (headache, asthenia, confusion, hallucinations, ataxia) with concurrent opportunistic diseases (neurotoxoplasmosis, disseminated Kaposi's sarcoma, disseminated CMV infection). CMV CNS involvement was not initially considered given the observed multiple comorbidities: antiviral treatment duration was probably not adequate given the end-organ disease. Concomitantly, plasma CMV DNA was undetectable while cerebrospinal fluid viral load was 31,340 copies/ml. Ganciclovir treatment followed by oral valganciclovir maintenance was associated with the slow disappearance of symptoms, the improvement of MRI images and the persistent undetectability of CMV DNA. The case here reported highlights the challenges of diagnosing CMV encephalitis in HIV-positive patients (with several cerebral comorbidities), the incomplete knowledge of the appropriate treatment for such a disease and the possibility of CMV replication in the cerebrospinal fluid despite undetectable plasma CMV DNA.

Mortality in patients with early- or late-onset candidaemia.

OBJECTIVES: Although candidaemia is a well-known complication of hospital stay and has a crude mortality of ∼40%, few data are available for episodes diagnosed within 10 days after hospital admission. In this paper, we compared the risk factors for mortality according to the onset of candidaemia. METHODS: This was a retrospective study of hospitalized patients with early-onset candidaemia (EOC; ≤ 10 days) or late-onset candidaemia (LOC; >10 days) to identify any distinct clinical characteristics and risk factors for 30 day mortality in two Italian academic centres. RESULTS: A total of 779 patients were included in the study: 183 EOC and 596 LOC. Mortality was significantly lower in EOC (71/183, 38.8% versus 283/596, 47.5%, P=0.03). In EOC, multivariate analysis showed that inadequate initial antifungal therapy (IIAT) (P=0.005, OR 3.02, 95% CI 1.40-6.51), Candida albicans aetiology (P=0.02, OR 2.17, 95% CI 1.11-4.26) and older age (P<0.001, OR 1.05, 95% CI 1.02-1.07) were independent risk factors for mortality. In LOC, liver disease (P=0.003, OR 2.46, 95% CI 1.36-4.43), IIAT (P=0.002, OR 2.01, 95% CI 1.28-3.15) and older age (P<0.001, OR 1.03, 95% CI 1.02-1.04) were independently associated with a fatal outcome, while treatment with caspofungin was associated with survival (P<0.001, OR 0.42, 95% CI 0.26-0.67). CONCLUSIONS: EOC has different clinical characteristics and risk factors for mortality compared with LOC. Although EOC mortality is significantly lower, the rate of inappropriate antifungal treatment is higher. Treatment with caspofungin is significantly associated with survival in patients with LOC. Efforts are needed to improve the diagnosis and treatment of EOC.

Anidulafungin treatment in a kidney transplant recipient with hepatic damage.

A 50-year old female was treated with anidulafungin after fluconazole treatment, for a complex clinical picture and immunosuppression. Anidulafungin was chosen when liver function test was abnormal in a setting of multiple causes of liver toxicity.