Colonisation with Extended-Spectrum Cephalosporin-Resistant Enterobacterales and Infection Risk in Surgical Patients: A Systematic Review and Meta-analysis.

INTRODUCTION: Limited evidence has been reported for surgical site infections (SSIs) in patients undergoing surgery who are carriers of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E). A systematic review and meta-analysis were conducted to evaluate the risk of postoperative infections in adult inpatients colonised with ESCR-E before surgery. METHODS: The Medline, Embase and Cochrane databases were searched between January 2011 and April 2022, following PRISMA indications. Random effects meta-analysis was used to quantify the association between ESCR-E colonisation and infection. RESULTS: Among the 467 articles reviewed, 9 observational studies encompassing 7219 adult patients undergoing surgery were included. The ESCR-E colonisation rate was 13.7% (95% CI 7.7-19.7). The most commonly reported surgeries included abdominal surgery (44%) and liver transplantation (LT; 33%). The SSI rate was 23.2% (95% CI 13.2-33.1). Pooled incidence risk was 0.36 (95% CI 0.22-0.50) vs 0.13 (95% CI 0.02-0.24) for any postoperative infection and 0.28 (95% CI 0.18-0.38) vs 0.17 (95% CI 0.07-0.26) for SSIs in ESCR-E carriers vs noncarriers, respectively. In ESCR-E carriers, the ESCR-E infection ratio was 7 times higher than noncarriers. Postoperative infection risk was higher in carriers versus noncarriers following LT. Sources of detected heterogeneity between studies included ESCR-E colonisation and the geographic region of origin. CONCLUSIONS: Patients colonised with ESCR-E before surgery had increased incidence rates of post-surgical infections and SSIs compared to noncarriers. Our results suggest considering the implementation of pre-surgical screening for detecting ESCR-E colonisation status according to the type of surgery and the local epidemiology.

ESCMID/EUCIC clinical practice guidelines on perioperative antibiotic prophylaxis in patients colonized by multidrug-resistant Gram-negative bacteria before surgery.

SCOPE: The aim of the guidelines is to provide recommendations on perioperative antibiotic prophylaxis (PAP) in adult inpatients who are carriers of multidrug-resistant Gram-negative bacteria (MDR-GNB) before surgery. METHODS: These evidence-based guidelines were developed after a systematic review of published studies on PAP targeting the following MDR-GNB: extended-spectrum cephalosporin-resistant Enterobacterales, carbapenem-resistant Enterobacterales (CRE), aminoglycoside-resistant Enterobacterales, fluoroquinolone-resistant Enterobacterales, cotrimoxazole-resistant Stenotrophomonas maltophilia, carbapenem-resistant Acinetobacter baumannii (CRAB), extremely drug-resistant Pseudomonas aeruginosa, colistin-resistant Gram-negative bacteria, and pan-drug-resistant Gram-negative bacteria. The critical outcomes were the occurrence of surgical site infections (SSIs) caused by any bacteria and/or by the colonizing MDR-GNB, and SSI-attributable mortality. Important outcomes included the occurrence of any type of postsurgical infectious complication, all-cause mortality, and adverse events of PAP, including development of resistance to targeted (culture-based) PAP after surgery and incidence of Clostridioides difficile infections. The last search of all databases was performed until April 30, 2022. The level of evidence and strength of each recommendation were defined according to the Grading of Recommendations Assessment, Development and Evaluation approach. Consensus of a multidisciplinary expert panel was reached for the final list of recommendations. Antimicrobial stewardship considerations were included in the recommendation development. RECOMMENDATIONS: The guideline panel reviewed the evidence, per bacteria, of the risk of SSIs in patients colonized with MDR-GNB before surgery and critically appraised the existing studies. Significant knowledge gaps were identified, and most questions were addressed by observational studies. Moderate to high risk of bias was identified in the retrieved studies, and the majority of the recommendations were supported by low level of evidence. The panel conditionally recommends rectal screening and targeted PAP for fluoroquinolone-resistant Enterobacterales before transrectal ultrasound-guided prostate biopsy and for extended-spectrum cephalosporin-resistant Enterobacterales in patients undergoing colorectal surgery and solid organ transplantation. Screening for CRE and CRAB is suggested before transplant surgery after assessment of the local epidemiology. Careful consideration of the laboratory workload and involvement of antimicrobial stewardship teams before implementing the screening procedures or performing changes in PAP are warranted. High-quality prospective studies to assess the impact of PAP among CRE and CRAB carriers performing high-risk surgeries are advocated. Future well-designed clinical trials should assess the effectiveness of targeted PAP, including the monitoring of MDR-GNB colonization through postoperative cultures using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints.

Long-Term Patient-Centred Follow-up in a Prospective Cohort of Patients with COVID-19.

INTRODUCTION: To better define COVID-19 long-term impact we prospectively analysed patient-centred outcomes, including general health and symptom duration. METHODS: Barthel index (BI), St. George's Respiratory Questionnaire adapted to patients with COVID-19 (aSGRQ) and WHO Clinical Progression Scale (CPS) were measured at enrolment and at 6 weeks from the onset of symptoms. Persistence of most frequently reported symptoms was assessed at 6 weeks and, among symptomatic patients, at 12 weeks from the onset of symptoms. Predictors of impaired general health over time were identified using an ordinal multilevel multivariate model. RESULTS: A total of 448 patients (55% men, median age 56 years) were enrolled. WHO-CPS showed mild, moderate and severe disease in 48%, 42% and 10% of patients at admission and mild disease in all patients at follow-up, respectively. BI and aSGRQ were normal in 96% and 93% patients before COVID-19 but only in 47% and 16% at COVID-19 diagnosis and in 87% and 65% at 6-week follow-up. Male gender was identified by all three assessments as a predictor of impaired general health (BI, OR 2.14, p < 0.0001; aSGRQ, OR 0.53, p = 0.003; WHO-CPS, OR 1.56, p = 0.01). Other predictors included age, ICU admission and comorbidities (e.g. cardiovascular disease and cancer) for BI, hospital admission for aSGRQ, age and presence of comorbidities for WHO-CPS. At 6- and 12-week follow-up, 39% and 20% of patients, respectively, were still reporting symptoms. Fatigue and breathlessness were the most frequently reported symptoms. CONCLUSIONS: Long-term follow-up facilitates the monitoring of health impairment and symptom persistence and can contribute to plan tailored interventions.

A Review of Vaccinations in Adult Patients with Secondary Immunodeficiency.

Vaccine-preventable diseases and their related complications are associated with increased morbidity and mortality in patients with altered immunocompetence. Optimised immunisation in this patient population is challenging because of limited data from vaccine trials, suboptimal vaccine efficacy and safety concerns. Reliable efficacy data are lacking among patients with altered immunocompetence, and existing recommendations are mainly based on expert consensus and may vary geographically. Inactivated vaccines can be generally used without risks in this group, but their efficacy may be reduced, and immunisation schedules vary according to local guidelines, age, and type and stage of the underlying disease. Live vaccines, if indicated, should be administered with care because of the risk of vaccine-associated disease. We have reviewed the current evidence on vaccination principles and recommendations in adult patients with secondary immunodeficiencies, including asplenia, HIV infection, stem cell and solid organ transplant, haematological malignancies, inflammatory bowel disease and other chronic disorders.

Pitfalls of Computed Tomography in the Coronavirus 2019 (COVID-19) Era: A New Perspective on Ground-Glass Opacities.

Aim To study ground-glass opacities (GGO) not only from the coronavirus 2019 (COVID-19) pneumonia" perspective but also as a radiological presentation of other pathologies with comparable features. Methods We enrolled 33 patients admitted to Policlinico Universitario G. B. Rossi who underwent non-contrast-enhanced (NCE) or contrast-enhanced (CE) chest computed tomography (CT) between March 12 and April 12. All patients with CT-detected ground-glass opacity (GGO) were included. All patients resulted as COVID-19 negative at the reverse transcription-polymerase chain reaction (RT-PCR) assay. We studied the different pathologies underlying GGO features: neoplastic diseases and non-neoplastic diseases (viral pneumonias, interstitial pneumonias, and cardiopulmonary diseases) in order to avoid pitfalls and to reach the correct diagnosis. Results All CT scans detected GGOs. Symptomatic patients were 25/33 (75.7%). At the clinical presentation, they reported fever and dry cough; in six out of 25 cases, dyspnea was also reported (24%). Thirty-three (33; 100%) showed GGO at CT: 15/33 (45.45%) presented pure GGO, and 18/33 (54.54%) showed GGO with consolidation. The RT-PCR assay was negative in 100%. We investigated other potential underlying diseases to explain imaging features: neoplastic causes (8/33, 24.24%) and non-neoplastic causes, in particular, infectious pneumonias (16/33, 48,48 %, viral and fungal), interstitial pneumonias (4/33, 12,12%), and cardio-pulmonary disease (5/33, 15,15%). Conclusions GGO remains a diagnostic challenge. Although CT represents a fundamental diagnostic tool because of its sensitivity, it still needs to be integrated with clinical data to achieve the best clinical management. In the presence of typical imaging features (e.g. GGO and consolidation), the radiologist should focus on the pandemic and manage a suspect patient as COVID-19 positive until proven to be negative.

Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation.

BACKGROUND: The Controlling Nutritional Status (CONUT) score is a newly developed laboratory-derived immunonutritional score which has been validated as prognostic marker for survival and tumor recurrence in surgically treated patients with various tumor types, including hepatocellular carcinoma (HCC). The aim of the present study was to test the CONUT score performance in HCC patients treated with liver transplantation (LT). METHODS: A retrospective study on a bi-centers cohort of 280 HCC patients submitted to LT between 2006 and 2017 was performed. Indication to LT was limited to Milan criteria or UCSF criteria, defined by preoperative imaging. RESULTS: Median pre-LT CONUT score was 5 (interquartile range 3-7). Overall patients' survival at 1, 3, and 5 years was 84%, 76.6%, and 68.3%, respectively. Multivariate analysis showed that HCC recurrence (hazard ratio [HR] = 1.987, P = .012] and pre-LT neutrophil to lymphocyte ratio (NLR) (HR = 1.064, P = .003) were independent risk factors for reduced survival. Cumulative incidence of HCC recurrence at 1, 3, and 5 years was 5.1%, 11.5%, and 15.5%, respectively. Pre-LT platelet-to-lymphocyte ratio (PLR) (subdistribution hazard ratio [SHR] = 1.086, P = .044], tumor max diameter (SHR = 1.695, P < .001), and bilobar tumor distribution (SHR = 6.892, P = .006) were independent risk factors for tumor recurrence. The CONUT score did not show any prognostic value. CONCLUSIONS: The CONUT score did not predict poor survival or tumor recurrence in LT recipients.

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).

Surgical Complications Requiring an Early Relaparotomy in HIV-Infected Liver Transplant Recipients: Risk Factors and Impact on Survival.

AIM: We aimed to analyze the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV-infected patients submitted to liver transplantation. METHODS: We performed a retrospective study on a nationwide multicenter cohort of 157 HIV-infected patients submitted to liver transplantation in 6 Italian transplant units between 2004 to 2014. RESULTS: The median preoperative model for end-stage liver disease score was 18 (interquartile range 12-26.5). An early relaparotomy was performed in 24.8% of patients, and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%), and suspected vascular complications (3.8%). The OS at 1, 3, and 5 years was 74.3%, 68.0%, and 60.0%, respectively, and an early relaparotomy was not a prognostic factor itself, but an increasing number of relaparotomies was associated with decreased survival (hazard ratio = 1.40, 95% confidence interval [CI] 1.07-1.81, P = .01). In the multivariate analysis, preoperative refractory ascites (odds ratio 3.32, 95% CI 1.18-6.47, P = .02) and Roux-en-Y choledochojejunostomy reconstruction (odds ratio 12.712, 95% CI 2.47-65.38, P ≤ .01) were identified as significant risk factors for early relaparotomy. CONCLUSIONS: In HIV-infected liver transplant recipients, an increasing number of early relaparotomies due to surgical complications did negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux-en-Y choledochojejunostomy were associated with an increased risk of early relaparotomy.

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.

Issues in the management of invasive pulmonary aspergillosis in non-neutropenic patients in the intensive care unit: A role for isavuconazole.

Background: Almost half of all cases of invasive aspergillosis (IA) occur in the intensive care unit (ICU), with mortality rates of 70-80% for probable or proven cases. IA has become a major concern among non-neutropenic patients in the ICU with chronic obstructive pulmonary disease (COPD) but although prompt, appropriate antifungal therapy is crucial, diagnosis in this situation is challenging. Criteria for a probable diagnosis in critically ill patients have been proposed to help to expedite therapy. Methods: A case of probable invasive pulmonary aspergillosis (IPA) in a non-neutropenic patient admitted to the ICU was used to illustrate potential issues in the diagnostic work-up and management of patients in this setting. Results: A non-neutropenic 69-year-old man with COPD receiving clomipramine was diagnosed in the ICU with probable invasive aspergillosis based on the presence of severe chronic obstructive pulmonary disease, suspected X-linked granulomatous disease, nodular infiltrates and galactogamman positivity on bronchoalveolar lavage (BAL) fluid. Voriconazole was unsuitable due to the patient's prolonged QT interval and risk of a drug-drug interaction with clomipramine. Isavuconazole was initiated and the patient's condition improved. The three-month course of isavuconazole treatment was well-tolerated and resulted in compete recovery of the patient. Conclusions: Voriconazole is a standard first-line treatment for IA but intravenous therapy is associated with toxicity and the potential for drug-drug interactions. Isavuconazole is another first-line therapy which was effective and safe in the management of this critically ill non-neutropenic patient with baseline QT prolongation and potential drug-drug interactions with voriconazole.

Ileocecal Fistula Caused by Multiple Foreign Magnetic Bodies Ingestion.

The incidence of accidental foreign body (FBs) ingestion is 100,000 cases/year in the US, with over than 80% of cases occurring in children below 5 years of age. Although a single FB may pass spontaneously and uneventfully through the digestive tract, the ingestion of multiple magnetics can cause serious morbidity due to proximate attraction through the intestinal wall. Morbidity and mortality depend on a prompt and correct diagnosis which is often difficult and delayed due to the patient's age and because the accidental ingestion may go unnoticed. We report our experience in the treatment of an 11-year-old child who presented to the emergency department with increasing abdominal pain, vomiting, diarrhea, and fever. Surgery evidenced an ileocecal fistula secondary to multiple magnetic FB ingestion with attraction by both sides of the intestinal wall. A 5-centimeter ileal resection was performed, and the cecal fistula was closed with a longitudinal manual suture. The child was discharged at postoperative day 8. After one year, the patient's clinical condition was good.

Successful treatment and FDG-PET/CT monitoring of HHV-6 encephalitis in a non-neutropenic patient: case report and literature review.

Human herpesvirus (HHV)-6 reactivation is associated with severe forms of encephalitis among patients undergoing hematopoietic stem cell transplantation. Cases in non-neutropenic patients are uncommon. The efficacy of ganciclovir and other compounds that are used for the treatment of HHV-6 encephalitis remains suboptimal and linked to toxicity. Valganciclovir, the oral prodrug of ganciclovir, could be practical to treat outpatients, but it is not commonly used for severe cases. We report a case of HHV-6 encephalitis in a non-neutropenic patient successfully treated with valganciclovir and undergoing therapeutic drug monitoring in plasma and in the cerebrospinal fluid. Resolution of infectious foci was documented by cerebral MRI and F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). A review of the literature on HHV-6 encephalitis is also reported.

Higher fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tuberculous compared to bacterial spondylodiscitis.

BACKGROUND: Tuberculous spondylodiscitis can be difficult to diagnose because of its nonspecific symptoms and the similarities with non-tubercular forms of spinal infection. Fluorine-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is increasingly used for the diagnosis and monitoring of tubercular diseases. METHODS: Retrospective, case-control study comparing tuberculous spondylodiscitis with biopsy-confirmed pyogenic spondylodiscitis in the period 2010-2012. RESULTS: Ten cases of tuberculous spondylodiscitis and 20 controls were included. Compared to pyogenic, tuberculous spondylodiscitis was more frequent in younger patients (P = 0.01) and was more often associated with thoraco-lumbar tract lesions (P = 0.01) and multiple vertebral involvement (P = 0.01). Significantly higher maximum standardized uptake values (SUV) at FDG-PET were displayed by tuberculous spondylodiscitis compared to controls (12.4 vs. 7.3, P = 0.003). SUV levels above 8 showed the highest value of specificity (0.80). Mean SUV reduction of 48% was detected for tuberculous spondylodiscitis at 1-month follow-up. CONCLUSIONS: Higher SUV levels at FDG-PET were detected in tuberculous compared with pyogenic spondylodiscitis. PET-CT use appeared useful in the disease follow-up after treatment initiation.

18F-Fluorodeoxyglucose positron emission tomography and infectious diseases: current applications and future perspectives.

PURPOSE OF REVIEW: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography is a well-established technique for diagnosis and management of a number of neoplastic conditions. However, in recent years the body of literature regarding its potential role in infectious diseases has progressively increased, with promising results. RECENT FINDINGS: So far 18F-fluorodeoxyglucose positron emission tomography/computed tomography has a well-established role and is recommended by guidelines only in a few settings, such as prosthetic valve endocarditis, vascular device infections, and chronic osteomyelitis. However, even the lack of large, prospective randomized trials, an increasing number of small series and case reports suggest a potential role in the diagnosis, disease staging, and monitoring of treatment response of several other infective conditions. SUMMARY: In this article, we summarize the available evidence and potential future applications of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the diagnosis and management of infectious diseases.

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.

Development of novel antibacterial drugs to combat multiple resistant organisms.

BACKGROUND: Infections due to multidrug-resistant (MDR) bacteria are increasing both in hospitals and in the community and are characterized by high mortality rates. New molecules are in development to face the need of active compounds toward resistant gram-positive and gram-negative pathogens. In particular, the Infectious Diseases Society of America (IDSA) has supported the initiative to develop ten new antibacterials within 2020. Principal targets are the so-called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacteriaceae). PURPOSE: To review the characteristics and the status of development of new antimicrobials including new cephalosporins, carbapenems, beta-lactamase inhibitors, aminoglycosides, quinolones, oxazolidones, glycopeptides, and tetracyclines. CONCLUSIONS: While numerous new compounds target resistant gram-positive pathogens and have been approved for clinical use, very few new molecules are active against MDR gram-negative pathogens, especially carbapenemase producers. New glycopeptides and oxazolidinones are highly efficient against methicillin-resistant S. aureus (MRSA), and new cephalosporins and carbapenems also display activity toward MDR gram-positive bacteria. Although new cephalosporins and carbapenems have acquired activity against MRSA, they offer few advantages against difficult-to-treat gram-negatives. Among agents that are potentially active against MDR gram-negatives are ceftozolane/tazobactam, new carbapenems, the combination of avibactam with ceftazidime, and plazomicin. Since a relevant number of promising antibiotics is currently in development, regulatory approvals over the next 5 years are crucial to face the growing threat of multidrug resistance.

Pros and cons of liver transplantation in human immunodeficiency virus infected recipients.

Before the introduction of combined highly active antiretroviral therapy, a positive human immunodeficiency virus (HIV) serological status represented an absolute contraindication for solid organ transplant (SOT). The advent of highly effective combined antiretroviral therapy in 1996 largely contributed to the increased demand for SOT in HIV-positive individuals due to increased patients' life expectancy associated with the increasing prevalence of end-stage liver disease (ESLD). Nowadays, liver failure represents a frequent cause of mortality in the HIV-infected population mainly due to coinfection with hepatitis viruses sharing the same way of transmission. Thus, liver transplantation (LT) represents a reasonable approach in HIV patients with stable infection and ESLD. Available data presently supports with good evidence the practice of LT in the HIV-positive population. Thus, the issue is no longer "whether it is correct to transplant HIV-infected patients", but "who are the patients who can be safely transplanted" and "when is the best time to perform LT". Indeed, the benefits of LT in HIV-infected patients, especially in terms of mid- and long-term patient and graft survivals, are strictly related to the patients' selection and to the correct timing for transplantation, especially when hepatitis C virus coinfection is present. Aim of this article is to review the pros and cons of LT in the cohort of HIV infected recipients.