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Since first identified in early 1977, bacteria of the genus Legionella are recognised as a common cause of community-acquired pneumonia and a rare cause of hospital-acquired pneumonia. Legionella bacteria multisystem manifestations mainly affect susceptible patients as a result of age, underlying debilitating conditions, or immunosuppression. Water is the major natural reservoir for Legionella, and the pathogen is found in many different natural and artificial aquatic environments such as cooling towers or water systems in buildings, including hospitals. The term given to the severe pneumonia and systemic infection caused by Legionella bacteria is Legionnaires' disease. Over time, the prevalence of legionellosis or Legionnaires' disease has risen, which might indicate a greater awareness and reporting of the disease. Advances in microbiology have led to a better understanding of the ecological niches and pathogenesis of the condition. Legionnaires' disease is not always suspected because of its non-specific symptoms, and the diagnostic tests routinely available do not offer the desired sensitivity. However, effective antibiotics are available. Disease notification systems provide the basis for initiating investigations and limiting the scale and recurrence of outbreaks. This report reviews our current understanding of this disease.

Purpose To describe the current standards of care and major recent advances with regard to antimicrobial resistance (AMR) and to give a prospective overview for the next 30 years in this field. Methods Review of medical literature and expert opinion were used in the development of this review. Results There is undoubtedly a large clinical and public health burden associated with AMR in ICU, but it is challenging to quantify the associated excess morbidity and mortality. In the last decade, antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant Gram-negative bacteria (GNB), in particular carbapenem-resistant Pseudomonas aeruginosa (and other non-fermenting GNB), extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE). The situation appears more optimistic currently for Gram-positive, where Staphylococcus aureus , and particularly methicillin-resistant S. aureus (MRSA), remains a cardinal cause of healthcare-associated infections worldwide. Recent advancements in laboratory techniques allow for a rapid identification of the infecting pathogen and antibiotic susceptibility testing. Their impact can be particularly relevant in settings with prevalence of MDR, since they may guide fine-tuning of empirically selected regimen, facilitate de-escalation of unnecessary antimicrobials, and support infection control decisions. Currently, antibiotics are the primary anti-infective solution for patients with known or suspected MDR bacteria in intensive care. Numerous incentives have been provided to encourage researchers to work on alternative strategies to reverse this trend and to provide a means to treat these pathogens. Although some promising antibiotics currently in phase 2 and 3 of development will soon be licensed and utilized in ICU, the continuous development of an alternative generation of compounds is extremely important. There are currently several promising avenues available to fight antibiotic resistance, such as faecal microbiota, and phage therapy.

Bezlotoxumab is human monoclonal antibody against Clostridium difficile toxin B. In two controlled trials, a single intravenous dose of bezlotoxumab, given in addition to antibiotic treatment, provided protection against recurrent infection for up to 12 weeks.

We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital and assessed the microbiological characteristics of the isolates. We recorded the incidence of mucormycosis and clinical and microbiological data of infected patients. Isolates were identified to molecular level and tested for their antifungal susceptibility to azoles, amphotericin B, and liposomal amphotericin B according to the CLSI M-38 A2 procedure. The incidence of mucormycosis in cases/100,000 hospital admissions during 2007-2015 increased significantly with respect to that reported in 1988-2006 (3.3 vs. 1.2; P<0.05). Patients mainly had hematological malignancies (52.6%) and/or trauma/surgical wounds (52.6%) and had received antifungal agents before the diagnosis of mucormycosis in 68% of cases. Diagnosis was by isolation (n = 17/19) and/or direct staining (n = 17/18) of Mucorales fungi in clinical samples. Identification was by panfungal PCR in patients with negative results in culture and in direct staining. The microorganisms identified were Lichtheimia spp. (42%), Rhizopus spp. (21%), Cunninghamella bertholletiae (16%), and others (21%). Liposomal amphotericin B was always more active than the other drugs against all the microorganisms except C. bertholletiae. All patients received antifungal treatment with 1 or more antifungal agents, mainly liposomal amphotericin B (17/19). Mortality was 47.4%, although this was significantly lower in the 11 patients in whom debridement was performed (18% vs. 87.5%) (P = 0.015). The incidence of mucormycosis has risen in recent years. The proportion of cases with soft tissue involvement was high, and Lichtheimia was the most frequently involved species. The highest antifungal activity was observed with liposomal amphotericin B.

These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.

Variations in testing for Clostridium difficile infection can hinder patients' care, increase the risk of transmission, and skew epidemiological data. We aimed to measure the underdiagnosis of C difficile infection across Europe. We did a questionnaire-based study at 482 participating hospitals across 20 European countries. Hospitals were questioned about their methods and testing policy for C difficile infection during the periods September, 2011, to August, 2012, and September, 2012, to August, 2013. On one day in winter, 2012–13 (December, 2012, or January, 2013), and summer, 2013 (July or August), every hospital sent all diarrhoeal samples submitted to their microbiology laboratory to a national coordinating laboratory for standardised testing of C difficile infection. Our primary outcome measures were the rates of testing for and cases of C difficile infection per 10 000 patient bed-days. Results of local and national C difficile infection testing were compared with each other. If the result was positive at the national laboratory but negative at the local hospital, the result was classified as undiagnosed C difficile infection. We compared differences in proportions with the Mann-Whitney test, or McNemar's test if data were matched. During the study period, participating hospitals reported a mean of 65·8 tests (country range 4·6–223·3) for C difficile infection per 10 000 patient-bed days and a mean of 7·0 cases (country range 0·7–28·7) of C difficile infection per 10 000 patient-bed days. Only two-fifths of hospitals reported using optimum methods for testing of C difficile infection (defined by European guidelines), although the number of participating hospitals using optimum methods increased during the study period, from 152 (32%) of 468 in 2011–12 to 205 (48%) of 428 in 2012–13. Across all 482 European hospitals on the two sampling days, 148 (23%) of 641 samples positive for C difficile infection (as determined by the national laboratory) were not diagnosed by participating hospitals because of an absence of clinical suspicion, equating to about 74 missed diagnoses per day. A wide variety of testing strategies for C difficile infection are used across Europe. Absence of clinical suspicion and suboptimum laboratory diagnostic methods mean that an estimated 40 000 inpatients with C difficile infection are potentially undiagnosed every year in 482 European hospitals. Astellas Pharmaceuticals Europe.

Purpose Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce. Methods We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011–2013) including patients from ICU, medical, and surgical wards. Results A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans ( n  = 308 isolates, 64 %) and C. glabrata ( n  = 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03–1.07, P  < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01–1.08, P  = 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02–2.89, P  = 0.019), septic shock (OR 3.29, 95 % CI 1.88–5.86, P  < 0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01–5.63, P  < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy. Conclusions Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

Background.Treatment of invasive mold infection in immunocompromised patients remains challenging. Voriconazole has been shown to have efficacy and survival benefits over amphotericin B deoxycholate, but its utility is limited by drug interactions. Liposomal amphotericin B achieves maximum plasma levels at a dosage of 10 mg/kg per day, but clinical efficacy data for higher doses are lacking. Methods.In a double-blind trial, patients with proven or probable invasive mold infection were randomized to receive liposomal amphotericin B at either 3 or 10 mg/kg per day for 14 days, followed by 3 mg/kg per day. The primary end point was favorable (i.e., complete or partial) response at the end of study drug treatment. Survival and safety outcomes were also evaluated. Results.Of 201 patients with confirmed invasive mold infection, 107 received the 3-mg/kg daily dose, and 94 received the 10-mg/kg daily dose. Invasive aspergillosis accounted for 97% of cases. Hematological malignancies were present in 93% of patients, and 73% of patients were neutropenic at baseline. A favorable response was achieved in 50% and 46% of patients in the 3- and 10-mg/kg groups, respectively (difference, 4%; 95% confidence interval, -10% to 18%; P > .05); the respective survival rates at 12 weeks were 72% and 59% (difference, 13%; 95% confidence interval, -0.2% to 26%; P > .05). Significantly higher rates of nephrotoxicity and hypokalemia were seen in the high-dose group. Conclusions.In highly immunocompromised patients, the effectiveness of 3 mg/kg of liposomal amphotericin B per day as first-line therapy for invasive aspergillosis is demonstrated, with a response rate of 50% and a 12-week survival rate of 72%. The regimen of 10 mg/kg per day demonstrated no additional benefit and higher rates of nephrotoxicity.

Tuberculosis is a serious opportunistic infection that may affect transplant recipients. The incidence of tuberculosis among such persons is 20-74 times higher than that for the general population, with a mortality rate of up to 30%. The most common form of acquisition of tuberculosis after transplantation is the reactivation of latent tuberculosis in patients with previous exposure. Clinical presentation is frequently atypical and diverse, with unsuspected and elusive sites of affection. Manifestations include fever of unknown origin and allograft dysfunction. Coinfection with other pathogens is not uncommon. New techniques, such as PCR and quantification of interferon-γ, have been developed to achieve more-rapid and -accurate diagnoses. Treatment requires control of interactions between antituberculous drugs and immunosuppressive therapy. Prophylaxis against latent tuberculosis is the main approach to treatment, but many issues remain unsolved, because of the difficulty in identifying patients at risk (such as those with nonreactive purified protein derivative test results) and the toxicity of therapy.

Background. It has been accepted that the infection by Mycobacterium tuberculosis (M. tuberculosis) can be more heterogeneous than considered. The emergence of clonal variants caused by microevolution events leading to population heterogeneity is a phenomenon largely unexplored. Until now, we could only superficially analyze this phenomenon by standard fingerprinting (RFLP and VNTR). Methods. In this study we applied whole genome sequencing for a more in-depth analysis of the scale of microevolution both at the intrapatient and interpatient scenarios. Results. We found that the amount of variation accumulated within a patient can be as high as that observed between patients along a chain of transmission. Intrapatient diversity was found both at the extrapulmonary and respiratory sites, meaning that this variability can be transmitted and impact on the inference of transmission events. One of the events studied allowed us to track for a single strain the complete process of (i) interpatient microevolution, (ii) intrapatient respiratory variation, and (iii) isolation of different variants at different infected sites of this patient. Conclusions. Our study adds new data to the understanding of variability in M. tuberculosis in a wide clinical scenario and alerts about the difficulties of establishing thresholds to differentiate relatedness in M. tuberculosis with epidemiological purposes.