Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018).

Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.

Systematic influenza screening in cardiac intensive care units during the influenza season: A prospective study in Spain.

BACKGROUND: Little is known about the incidence of influenza among admissions to the cardiac intensive care unit (C-ICU), accuracy of clinical suspicion, and influenza vaccination uptake. We evaluated the incidence of influenza at C-ICU admission during the influenza season, potential underdiagnosis, and vaccination uptake. METHODS: Prospective study at five C-ICUs during the 2017-2020 influenza seasons. A nasopharyngeal swab was collected at admission from patients who consented (n = 788). Testing was with Xpert®XpressFlu/RSV. RESULTS: Influenza was detected in 43 patients (5.5%) (40 FluA; 3 FluB) and clinically suspected in 27 (62.8%). Compared to patients without influenza, patients with influenza more frequently had heart failure (37.2% vs 22.8%, P = 0.031), previous contact with relatives with influenza-like illnesses (23.3% vs 12.5%, P = 0.042), antimicrobial use (67.4% vs 23.2%, P <0.01), and need for mechanical ventilation (25.6% vs 14.5%, P = 0.048). Patients received oseltamivir promptly. We found no differences in mortality (11.6% vs 5.2%, P = 0.076). Patients with influenza more frequently had myocarditis (9.3% vs 0.9%, P <0.01) and pericarditis (7.0% vs 0.8%, P = 0.01). Overall, 43.0% of patients (339/788) were vaccinated (51.9% of those with a clear indication [303/584]). CONCLUSION: Influenza seems to be a frequently underdiagnosed underlying condition in admissions to the C-ICU. Influenza should be screened for at C-ICU admission during influenza epidemics.

Staphylococcus aureus surgical site infection rates in 5 European countries.

OBJECTIVE: To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe. METHODS: This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case-control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching. RESULTS: A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure. CONCLUSIONS: This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017).

Comparative study of the etiology of nosocomial bacteremic pneumonia in ventilated and non-ventilated patients: a 10-year experience in an institution.

IMPORTANCE: This study on bacteremic nosocomial pneumonia (bNP) demonstrates the importance of this condition both in patients undergoing and not undergoing mechanical ventilation. Staphylococcus aureus, Enterobacterales, and non-fermenting Gram-negative bacilli are all causative agents in ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP), with a predominance of S. aureus in HAP and of Pseudomonas aeruginosa in VAP. Mortality in this condition is very high. Therefore, new therapeutic and preventive approaches should be sought.

In vitro study to assess modulation of Candida biofilm by Escherichia coli from vaginal strains.

Background: Vulvovaginal candidiasis (VVC) is caused by biofilm formation and epithelial invasion. In addition, Escherichia coli (EC) can establish a vaginal intracellular reservoir modulating Candida spp. biofilm production. We aimed to analyze the behavior of Candida albicans (CA) and EC biofilm both in single cultures and in co-cultures. Methods: We prospectively collected CA and EC isolates from vaginal swabs over 6 months. We selected positive cultures with both CA and EC (cases) and a comparator group with either CA or EC (controls). We analyzed overall biomass production and metabolic activity in single cultures and in co-cultures based on staining assays, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) to assess biofilm occupation. We also analyzed clinical manifestations. Results: We cultured 455 samples, 16 (3.5%) of which had CA and EC (cases); only CA or EC (controls) was detected, respectively, in 72 (15.8%) and 98 (21.5%). Biomass production and metabolic activity were significantly more pronounced in co-cultures in both groups. CLSM and SEM, on the other hand, showed the biofilm of each species to be significantly reduced when they were cultured together, with higher values in CA (percentage biofilm reduction: CA, 95.8% vs. EC, 36.2%, p < 0.001). There were no clinically significant differences between co-infected patients and patients infected only by C. albicans. Conclusion: Ours is the first study assessing co-cultures of CA and EC in a large collection of samples. We observed that coinfection of CA and EC was unusual (3.5%) and promoted high biomass, whereas microscopy enabled us to detect a reduction in biofilm production when microorganisms were co-cultured. No differences in symptoms were observed.

Nosocomial Infections in Adult Patients Supported by Extracorporeal Membrane Oxygenation in a Cardiac Intensive Care Unit.

The use of venoarterial (VA) extracorporeal membrane oxygenation therapy (ECMO) in patients admitted to cardiac intensive care units (CICU) has increased. Data regarding infections in this population are scarce. In this retrospective study, we analyzed the risk factors, outcome, and predictors of in-hospital mortality due to nosocomial infections in patients with ECMO admitted to a single coronary intensive care unit between July 2013 and March 2019 treated with VA-ECMO for >48 h. From 69 patients treated with VA-ECMO >48 h, (median age 58 years), 29 (42.0%) patients developed 34 episodes of infections with an infection rate of 0.92/1000 ECMO days. The most frequent were ventilator-associated pneumonia (57.6%), tracheobronchitis (9.1%), bloodstream infections (9.1%), skin and soft tissue infections (9.1%), and cytomegalovirus reactivation (9.1%). In-hospital mortality was 47.8%, but no association with nosocomial infections was found (p = 0.75). The number of days on ECMO (OR 1.14, 95% CI 1.01-1.30, p = 0.029) and noninfectious complications were higher in the infected patients (OR: 3.8 95% CI = 1.05-14.1). A higher baseline creatinine value (OR: 8.2 95% CI = 1.12-60.2) and higher blood lactate level at 4 h after ECMO initiation (OR: 2.0 95% CI = 1.23-3.29) were significant and independent risk factors for mortality. Conclusions: Nosocomial infections in medical patients treated with VA-ECMO are very frequent, mostly Gram-negative respiratory infections. Preventive measures could play an important role for these patients.

Aspergillus endocarditis in the recent years, report of cases of a multicentric national cohort and literature review.

OBJECTIVES: (1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality. METHODS: We recruited 10 AE cases included in the GAMES cohort (January 2008-December 2018) and 51 cases from the literature published from January 2010 to July 2019. RESULTS: 4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%). Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26-13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07-0.72, p = .01). CONCLUSIONS: AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole-based treatment combined with surgical resection are related to a better outcome.

SARS-COV-2 Infection in People Living with HIV: Experience from a Tertiary Hospital in Madrid.

Since SAR-COV-2 infection emerged and spread worldwide, little is known about its impact on people living with human immunodeficiency virus (HIV). We performed a single-center retrospective study to describe the potential particularities and risk factors for respiratory failure (RF) in that population. This single-center retrospective study included patients infected with HIV, whose current follow-up is run in this center, above18 years of age, with diagnosis of SARS-CoV-2 infection between March 5, 2020 and April 15, 2021. We collected data regarding HIV immunological and virological status, main epidemiological characteristics, as well as those conditions considered to potentially influence in SARS-CoV-2 evolution; and clinical, microbiological, radiological, respiratory status, and survival concerning coronavirus disease 2019 (COVID-19). We compared all that, for patients with and without RF and performed a logistic regression for suspected risk factors for RF. One hundred seventy-seven HIV patients were diagnosed from COVID-19 (mean age 53.8 years, 81.3% male). At diagnosis, 95.5% were receiving ART and 91.3% had undetectable viral load, with median CD4 count of 569 cells/µL. One hundred thirty-eight patients (78.4%) had symptoms, 44 (25%) developed RF and 53 (31%) developed bilateral pneumonia. The most commonly used treatments were: steroids (26.7%) and hydroxychloroquine (13.1%). When comparing patients with and without RF, we found statistically significant differences for 20 of the analyzed variables such as age (p < .001) and CD4 (p 0.002), and route of HIV transmission by intravenous drug users IVDU (p 0.002) were determined. In multivariate analysis, age [odds ratio (OR) 1.095] and CD4 count less than 350 cells/µL (OR 3.36) emerged as risk factor for RF. People living with HIV whose CD4 count is <350 cells are at higher risk of developing RF when infected by SARS-CoV-2.

Use of Saliva Swab for Detection of Influenza Virus in Patients Admitted to an Emergency Department.

Nasopharyngeal (NP) specimens are commonly used for the detection of influenza, but saliva swabs are easier to obtain and cause less discomfort to the patients. The objective of this study was to evaluate the usefulness of saliva swab specimens for the diagnosis of influenza compared with NP specimens. Influenza virus detection rate in saliva and NP swabs was compared in adult patients admitted to an emergency department from January to March 2020, using the Xpert Xpress Flu/respiratory syncytial virus (RSV) test. Cycle threshold (CT) values were evaluated in all the cases. Among the 82 patients recruited, 19 had an influenza-positive diagnostic test result (11 influenza A and 8 influenza B). Overall, the agreement between saliva and NP swabs results was 97.6% (80/82; κ = 0.929; 95% confidence interval [CI], 0.832 to 1.0). There was no significant difference in the influenza detection rate between saliva swab and NP specimens (20.7% [17/82] versus 23.2% [19/82]; P = 0.5). There were only two discordant results (influenza B in an NP and false negative in a saliva sample). Manual inspection of the amplification curves showed that influenza RNA had been amplified in saliva with high CTs (CT of 40) that the test reported as a negative result. The overall sensitivity and specificity for saliva was 89.5% (73.0% to 100%) and 100% (99.2% to 100%), respectively. In all the cases, the same influenza virus (A/B) was detected. Median CT values were significantly lower in NP (31; interquartile range [IQR], 21.0 to 32.0) than in saliva (33; IQR, 23.0 to 38.0) (P = 0.001) specimens. Saliva swabs have high sensitivity and specificity for the detection of influenza virus by the Xpert Xpress Flu/RSV test and a high overall agreement and CT correlation with NP specimens. Saliva swab is a feasible specimen type for influenza testing that might be easily self-collected with minimal equipment and discomfort. IMPORTANCE Early detection of influenza virus is important for guiding antiviral and antibacterial treatment for infection control and public health measures. We have observed that saliva swab specimens have high sensitivity and specificity for the detection of influenza by the Xpert Xpress Flu/respiratory syncytial virus (RSV) test and high overall agreement and CT correlation with nasopharyngeal specimens. Saliva swab may therefore be a feasible specimen type for influenza testing that can be easily self-collected with minimal equipment and discomfort.

Utility of 1,3 ß-d-Glucan Assay for Guidance in Antifungal Stewardship Programs for Oncologic Patients and Solid Organ Transplant Recipients.

The implementation of 1,3 ß-d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre-post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%; p = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29; p < 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, p = 0.04). All-cause mortality (44.7% vs. 34.8%; p = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 €/patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients.

Valganciclovir-Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship.

Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations.

Revisiting nocardiosis at a tertiary care institution: Any change in recent years?

OBJECTIVE: To analyse relevant changes in incidence, clinical and microbiological characteristics of nocardiosis over the last 24 years at the current institution. MATERIALS AND METHODS: The clinical records of patients with nocardiosis (2006-2018) were reviewed and then compared with a previous cohort (1995-2006). Nocardia isolates were identified by 5'-end-16S-rRNA-gene-PCR targeting the first 500 bp of the gene and sequencing. Susceptibility tests were determined by broth microdilution (CLSI guidelines). RESULTS: Forty-two patients (64.3% male) with nocardiosis were evaluated in the recent cohort: 51.2% had COPD, 43.9% were on corticosteroid therapy and 31.7% had cancer. The incidence of nocardiosis varied from 6.3 to 7.1/100,000 admissions (p = 0.62). There was a decrease in HIV patients (27% vs. 4.9%, p = 0.01) and solid organ transplantation (SOT) recipients (18.9% vs. 2 .4%, p = 0.01). Cases with pulmonary involvement had increased (70.3% vs. 90.5%, p = 0.04). Nocardia species were similar but the most common were N. cyriacigeorgica (32.4% vs. 40.5%, p = 0.49) and N. farcinica (24.3% vs. 14.3%, p = 0.39). Antibiotic resistance remained stable: cotrimoxazole (10.8% vs. 5.7%, p = 0.68), imipenem (5.4% vs. 5.6%, p = 1.0); amikacin and linezolid were 100% active. No differences were found in breakthrough nocardiosis (21.6% vs. 9.8%, p = 0.21) or related mortality (21.6% vs. 21.4%, p = 1.0). The multivariate analysis confirmed that nocardiosis caused by N. farcinica is a risk factor for poor outcome (p = 0.045). CONCLUSIONS: Nocardiosis incidence has remained stable. It mainly affected elderly patients with chronic respiratory conditions and those on corticosteroid treatment. Infections in HIV and SOT patients have practically disappeared. Pulmonary involvement remains the most common area to be affected. Nocardiosis caused by N. farcinica is apparently a risk factor for poor clinical outcome.

Invasive Scedosporium and Lomentosora infections in the era of antifungal prophylaxis: A 20-year experience from a single centre in Spain.

BACKGROUND: Non-Aspergillus mould infections such as those caused by Scedosporium apiospermum or Lomentospora prolificans are an emerging threat. Few studies have monitored their long-term incidence. OBJECTIVES: To analyse the epidemiology, risk factors, clinical features and incidence of patients with proven and probable infections. PATIENTS/METHODS: Patients admitted to Gregorio Marañón Hospital between 1998 and 2017 and from whom Scedosporium/Lomentospora was isolated were studied. Subjects were classified as having a probable/proven invasive fungal infection or colonization. Molecular identification and antifungal susceptibility testing of isolates causing infection were performed, as well as a description of the patients and incidence of infection. RESULTS: One or more Scedosporium/Lomentospora isolates were identified in 67 patients. Sixteen (23.9%) patients had developed infection: 11 scedosporiosis and 5 lomentosporiosis. Stable incidence was observed throughout the study period. Most patients were immunosuppressed and the most common underlying diseases were haematologic malignancy (25%), solid organ transplantation (25%) and chronic corticoid therapy (25%). Breakthrough infection occurred in four patients, 2/11 (18.2%) cases of scedosporiosis and 2/5 (40%) of lomentosporiosis. Overall mortality was 54.5% (6/11) and 80% (4/5) in subjects with scedosporiosis and lomentosporiosis, respectively. High MICs of amphotericin B and remarkable inter-species susceptibility variability to triazoles was observed for most isolates. CONCLUSIONS: In contrast to previous studies, the incidence of scedosporiosis and lomentosporiosis has not increased at our hospital over the years. The tendency to cause disseminated infection and a reduced susceptibility to most antifungal agents leads to high mortality.

Therapeutic Drug Monitoring of Antifungal Drugs: Another Tool to Improve Patient Outcome?

INTRODUCTION: This study aimed to examine the relationship among adequate dose, serum concentration and clinical outcome in a non-selected group of hospitalized patients receiving antifungals. METHODS: Prospective cross-sectional study performed between March 2015 and June 2015. Dosage of antifungals was considered adequate according to the IDSA guidelines, whereas trough serum concentrations (determined with HPLC) were considered adequate as follows: fluconazole > 11 µg/ml, echinocandins > 1 µg/ml, voriconazole 1-5.5 µg/ml and posaconazole > 0.7 µg/ml. RESULTS: During the study period, 84 patients (65.4% male, 59.6 years) received antifungals for prophylaxis (40.4%), targeted (31.0%) and empirical therapy (28.6%). The most frequent drug was micafungin (28/84; 33.3%) followed by fluconazole (23/84; 27.4%), voriconazole (15/84; 17.9%), anidulafungin (8/84; 9.5%), posaconazole (7/84; 8.3%) and caspofungin (3/84; 3.6%). Considerable interindividual variability was observed for all antifungals with a large proportion of the patients (64.3%) not attaining adequate trough serum concentrations, despite receiving an adequate antifungal dose. Attaining the on-target serum antifungal level was significantly associated with a favorable clinical outcome (OR = 0.02; 95% CI 0.01-0.64; p = 0.03), whereas the administration of an adequate antifungal dosage was not. CONCLUSIONS: With the standard antifungal dosage, a considerable proportion of patients have low drug concentrations, which are associated with poor clinical outcome.

A retrospective cohort of invasive fusariosis in the era of antimould prophylaxis.

Mould-active prophylaxis is affecting the epidemiology of invasive mycoses in the form of a shift toward less common entities such as fusariosis. We analyze the characteristics of invasive fusariosis and its association to antifungal prophylaxis in a retrospective cohort (2004-2017) from a tertiary hospital in Madrid, Spain. Epidemiological, clinical, microbiological, and antifungal consumption data were retrieved. Isolates were identified to molecular level, and antifungal susceptibility was tested. Eight cases of invasive fusariosis were diagnosed. Three periods were identified according to incidence: <2008 (three cases), 2008-2013 (zero cases), >2014 (five cases). All except one case involved breakthrough fusariosis. During the earliest period, the episodes occurred while the patient was taking itraconazole (two) or fluconazole (one); more recently, while on micafungin (three) or posaconazole (one). Early cases involved acute leukemia at induction/consolidation, recent cases relapsed/refractory disease (P = .029). Main risk factor for fusariosis (62.5%) was prolonged neutropenia (median 44 days). Galactomannan and beta-D-glucan were positive in 37.5% and 100% of cases, respectively. All isolates except F. proliferatum presented high minimal inhibitory concentrations (MICs) against the azoles and lower MIC to amphotericin B. Most patients received combined therapy. Mortality at 42 days was 62.5%. Resolution of neutropenia was associated with survival (P = .048). Invasive fusariosis occurs as breakthrough infection in patients with hematologic malignancy, prolonged neutropenia, and positive fungal biomarkers. Recent cases were diagnosed in a period of predominant micafungin use in patients who had more advanced disease and protracted neutropenia and for whom mortality was extremely high. Resolution of neutropenia was a favorable prognostic factor.

A multicentre analysis of Nocardia pneumonia in Spain: 2010-2016.

OBJECTIVE: To analyse all cases of Nocardia pneumonia occurring between 2010 and 2016 in five Spanish hospitals. METHODS: This was a retrospective observational analysis of clinical and microbiological data collected from 55 cases of Nocardia pneumonia. RESULTS: There were one to 20 cases per hospital and six to nine cases per year. Chronic obstructive pulmonary disease, bronchiectasis, and asthma were the main predisposing underlying respiratory conditions. Thirty-four patients were receiving systemic and/or inhaled corticosteroids prior to infection, eight had neoplasia, and six had haematological malignancies. Clinical and radiological findings were common to pneumonia of other infectious aetiologies, except for the frequent presence of nodules and cavitation. Overall, the 1-year mortality was high (38.2%), and mortality was directly related to the pulmonary disease in 15 patients (27.3%). The most frequently identified species were N. cyriacigeorgica (n=21), N. abscessus (n=8), and N. farcinica (n=5). All Nocardia isolates were susceptible to linezolid and all but two were susceptible to amikacin and trimethoprim-sulfamethoxazole. CONCLUSIONS: Nocardia pneumonia-associated mortality remains high, probably because of the debilitated status of patients in whom this pathogen is able to cause pulmonary infection.

Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals.

BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.

Methicillin-Resistant Staphylococcus aureus Prosthetic Valve Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management.

Staphylococcus aureus prosthetic valve endocarditis (PVE) remains among the most morbid bacterial infections, with mortality estimates ranging from 40% to 80%. The proportion of PVE cases due to methicillin-resistant Staphylococcus aureus (MRSA) has grown in recent decades, to account for more than 15% of cases of S. aureus PVE and 6% of all cases of PVE. Because no large studies or clinical trials for PVE have been published, most guidelines on the diagnosis and management of MRSA PVE rely upon expert opinion and data from animal models or related conditions (e.g., coagulase-negative Staphylococcus infection). We performed a review of the literature on MRSA PVE to summarize data on pathogenic mechanisms and updates in epidemiology and therapeutic management and to inform diagnostic strategies and priority areas where additional clinical and laboratory data will be particularly useful to guide therapy. Major updates discussed in this review include novel diagnostics, indications for surgical management, the utility of aminoglycosides in medical therapy, and a review of newer antistaphylococcal agents used for the management of MRSA PVE.

Current use of daptomycin and systematic therapeutic drug monitoring: Clinical experience in a tertiary care institution.

Therapeutic drug monitoring (TDM) could optimise daptomycin use. However, no validated serum target levels have been established. This prospective study at a tertiary centre including hospitalised patients receiving daptomycin aimed to evaluate the adequacy of daptomycin doses in a real-life study, assess interpatient variability in serum levels, identify predictive factors for non-adequate serum levels and assess their clinical impact. Blood samples [trough (Cmin) and peak (Cmax) levels] were drawn ≥3 days post-treatment initiation. Serum daptomycin concentrations were determined by HPLC. Outcome was classified as: (i) favourable, if clinical improvement or cure occurred with no adverse events; or (ii) poor, in the case of no clinical response, recurrence, related mortality or if adverse events were detected. Sixty-three patients (63.5% male; median age 63.0 years) were included. The most common indications for daptomycin use were bacteraemia (46.0%), complicated skin and soft-tissue infection (30.2%) and endovascular infection (15.9%). The initial dosage was adequate in 43 patients (68.3%), low in 14 (22.2%) and high in 6 (9.5%). Large interindividual variability in serum levels was observed, with a median Cmin of 10.6 mg/L (range 1.3-44.7 mg/L) and median Cmax of 44.0 mg/L (range 3.0-93.7 mg/L). Multivariate analysis showed that Cmin < 3.18 mg/L was independently related to poor outcome (OR = 6.465, 95% CI 1.032-40.087; P = 0.046). High variability in daptomycin use and serum levels was detected. Specific serum targets were identified as risk factors for poor outcome. TDM might be useful to optimise daptomycin doses and to avoid therapeutic failure.