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The present outbreak of Human Monkeypox (HMPX) that has begun in May 2022 and has spread across all continents in less than two months has qualitative and quantitative characteristics that make it different from the pattern of human disease previously caused by this virus. It has spread with enormous ease, affects almost exclusively adults, behaves as a sexually transmitted disease and focuses on very specific groups and transmission conditions. The high incidence in the city of Madrid in males that have sex with males (MSM) has allowed us to observe and report the experience with the first 30 cases diagnosed in our institution. Patients presented with febrile symptoms, genital and paragenital skin lesions reminiscent of smallpox, but less extensive and severe. The disease may also cause proctitis, pharyngitis and perioral lesions. The PCR test for diagnostic confirmation has been shown to be very sensitive and effective, not only in skin lesions but also in blood and other fluids such as pharyngeal, rectal exudates and blood. A very high proportion of patients with HMPX also have other sexually transmitted diseases that must be actively detected in this context. The spontaneous evolution of our patients has been good and hospitalization has been practically unnecessary. Transmission to non-sexual cohabitants and health personnel has been nonexistent and the lesions have disappeared in less than 30 days without leaving sequelae and no need for specific antiviral treatment.

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 (

SUMMARYThe currently expanding monkeypox epidemic is caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. In contrast to monkeypox cases caused by clade I and subclade IIa MPXV, the prognosis of current cases is generally favorable, but person-to-person transmission is much more efficient. MPXV evolution is driven by selective pressure from hosts and loss of virus–host interacting genes. However, there is no satisfactory genetic explanation using single-nucleotide polymorphisms (SNPs) for the observed increased MPXV transmissibility. We hypothesized that key genomic changes may occur in the genome’s low-complexity regions (LCRs), which are highly challenging to sequence and have been dismissed as uninformative. Using a combination of highly sensitive techniques, we determined a first high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This effort revealed significant variation in short-tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of SNPs and that LCRs are not randomly distributed.In silicoanalyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs) 153, 204, and 208 could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. Consequently, we posit that genomic studies focusing on phenotypic MPXV clade-/subclade-/lineage-/strain differences should change their focus to the study of LCR variability instead of SNP variability.

The standard RT-PCR assay for COVID-19 is laborious and time-consuming, limiting the availability of testing. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the reliability of the PanbioTM COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) for SARS-CoV-2 in nasopharyngeal swab specimens. This was a prospective multicenter study in ten Spanish university hospitals of patients from hospital units with clinical symptoms or epidemiological criteria for COVID-19. Patients whose onset of symptoms or exposure was more than 7 days earlier were excluded. Two nasopharyngeal exudate samples were taken to perform the PanbioRT and a diagnostic RT-PCR test. Among the 958 patients studied, 359 (37.5%) were positive by RT-PCR and 325 (33.9%) were also positive by the PanbioRT. Agreement was 95.7% (kappa score: 0.90). All 34 false-negative PanbioRT results were in symptomatic patients, with 23.5% of them at 6–7 days since the onset of symptoms and 58.8% presenting CT >30 values for RT-PCR, indicating a low viral load. Overall sensitivity and specificity for the PanbioRT were 90.5% and 98.8%, respectively. The PanbioRT provides good clinical performance as a point-of-care test, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. While this study has had a direct impact on the national diagnostic strategy for COVID-19 in Spain, the results must be interpreted based on the local epidemiological context.

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.

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 Maranon 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.

espanolAntecedentes. Existen pocas descripciones de la presentacion clinica y evolucion de infecciones consecutivas por SARS-CoV-2 con un seguimiento lo suficientemente largo. Metodos. Descripcion de los primeros 100 pacientes consecutivos con COVID-19 probada microbiologicamente en un gran hospital de Madrid, incluyendo un seguimiento minimo de dos meses. Resultados. La mediana de edad de los pacientes (52% hombres) fue de 61,5 anos (RIC=39,5-82,0) y la mediana de IMC fue de 28,8 kg/m2 (RIC=24,7-33,7). El 72% de los pacientes tuvieron una o mas comorbilidades con un indice de Charlson ajustado a la edad de 2 (RIC=0-5,7). Cinco pacientes (5%) estaban inmunodeprimidos. Los sintomas mas comunes al momento del diagnostico fueron fiebre (80,0%), tos (53,0%) y disnea (23,0%). La mediana de saturacion de O2 en el momento del primer examen fue del 94% (RIC=90-97). La radiografia de torax al ingreso fue compatible con neumonia en el 63% de los casos (bilateral en el 42% y unilateral en el 21%). El 30% fueron manejados en su domicilio y el 70% ingresados en el hospital. Trece pacientes ingresaron en la UCI con una mediana de 11 dias de estancia en la Unidad (RIC=6,0-28,0). El score CALL de nuestra poblacion vario de 4 a 13. En general, el 60,0% de los pacientes recibio tratamiento antibiotico y el 66,0%, tratamiento antiviral empirico, principalmente con lopinavir/ritonavir (65%) o hidroxicloroquina (42%). La mortalidad, con un minimo de 60 dias de seguimiento, fue del 23%. La mediana de edad de los pacientes fallecidos fue de 85 anos (RIC=79-93). Conclusiones. Encontramos una alta mortalidad en los primeros 100 pacientes diagnosticados con COVID-19 en nuestra institucion, asociada con edad avanzada y presencia de enfermedades subyacentes graves. EnglishBackground. There are few descriptions of the clinical presentation and evolution of consecutive SARS-CoV-2 infections with a long-enough follow up. Methods. Description of the first consecutive 100 patients with microbiologically-proven COVID-19 in a large hospital in Madrid, Spain including a minimum of two-month follow up. Results. The median age of the patients (52% males) was 61.5 years (IQR=39.5-82.0) and the median BMI was 28.8 kg/m2 (IQR=24.7-33.7). Overall 72% of the patients had one or more co-morbid conditions with a median age-adjusted Charlson index of 2 (IQR=0-5.7). Five patients (5%) were immunosuppressed. The most common symptoms at the time of diagnosis were fever (80.0%), cough (53.0%) and dyspnea (23.0%). The median O2 saturation at the time of first examination was 94% (IQR=90-97). Chest X-ray on admission was compatible with pneumonia in 63% of the cases (bilateral in 42% and unilateral in 21%). Overall, 30% were managed at home and 70% were admitted to the hospital. Thirteen patients were admitted to the ICU with a median of 11 days of stay in the Unit (IQR=6.0-28.0). CALL score of our population ranged from 4 to 13. Overall, 60.0% of patients received antibiotic treatment and 66.0%, empirical antiviral treatment, mainly with lopinavir/ritonavir (65%) or hydroxychloroquine (42%). Mortality, with a minimum of 60 days of follow up, was 23%. The median age of the deceased patients was 85 years (IQR=79-93). Conclusions. We found a high mortality in the first 100 patients diagnosed with COVID-19 at our institution, associated with advanced age and the presence of serious underlying diseases.

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.

(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.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 2019.4528 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).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.

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.

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

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

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.

The implementation of 1,3 &beta, 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&ndash, 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 &lt, 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 &euro, /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.

We communicate the interference of a compound of the blood collection tube with the accuracy of a validated high-pressure liquid chromatography method with ultraviolet detection for quantifying voriconazole levels, which led to false positive results. This could have serious consequences for patient management. Our advice is to implement external assessment programs.

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. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

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.

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: 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.

Background Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice. Methods MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis. Results There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators. Conclusion For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications.

Linezolid serum trough ( C min ) and peak ( C max ) levels were determined prospectively in 90 patients. Adequate exposure was defined as a C min of 2 to 8 mg/liter. Therapy was empirical (73.3%) or targeted (26.7%). Wide interindividual variability in linezolid C min levels was recorded (0.1 to 25.2 μg/ml). Overall, 65.5% of the patients had out-of-range, 41.1% had subtherapeutic, and 24.4% had supratherapeutic trough levels. We did not find a correlation between abnormal levels and adverse events, in-hospital mortality, or overall poor outcome.

Background Optimal hepatitis B (HBV) vaccination strategies for lung transplantation (LT) candidates are not well established. Methods LT candidates with negative anti-HBs and anti-HBc antibody titers at baseline who received standard-dose HBV vaccination (Recombivax-HB 10 mcg/mL or Engerix-B 20 mcg/mL) administered at months 0, 1, and 6 or an accelerated vaccination schedule on days 0, 7 to 14, and 21 to 28 between June 1988 and October 2012 were studied. Patients who were more likely to undergo LT within 6 months of evaluation received the accelerated vaccination schedule starting in August 2009. Results Ninety-six HBV-seronegative patients who completed the vaccination series and had postvaccination anti-HBs titers available were identified. Median age was 60 years; 55.2% were female, and 92.7% were white. Underlying lung diseases included COPD (44.8%), idiopathic pulmonary fibrosis (22.9%), interstitial lung disease (15.6%), and cystic fibrosis (8.3%). The overall anti-HBs response rate was 54.2%. There was no significant difference in vaccine responses between accelerated and standard vaccination schedules (54.2% vs. 54.1%; P=1.0). Patients who received steroids or other immunosuppressants before transplantation had lower response rates compared with those who did not (38.9% vs. 63.3%; P=0.03). Conclusions Better vaccination strategies to improve response rate are needed in this population. The accelerated HBV vaccination schedule elicited similar anti-HBs responses as the standard schedule and could be advantageous in this population, given current organ allocation practices, and it could allow repeat vaccination series for initial nonresponders before transplantation.

Background Daptomycin use has increased since its approval and has often extended to indications not included in the summary of product characteristics with highly variable dosing. Our objective was to assess daptomycin real use in an institution with Pharmacy and ID consultation available and to explore the need for establish specific Daptomycin stewardship. Methods Observational, retrospective study including all patients treated with daptomycin during 2017 in a tertiary hospital. Clinical variables were collected in a pre-established protocol including demographics, comorbidities, infection type, microbiological results, adverse events (AE), outcomes, and treatment adequacy (selection, dosage, microbiological adjustment and duration). Daptomycin prescription is not restricted at our institution. The dosages were considered adequate according to clinical guidelines. Results Overall 176 patients (62% men, median age: 70years) started treatment with daptomycin, 58% of them on empirical bases. Main uses were: skin and soft-tissue infections (37.5%), fever without obvious source (17.6%) and osteoarticular infection (12.5%). Sixty-three patients (35.8%) had concomitant bacteremia. An etiologic diagnosis was reached in 89.2% patients and S.aureuswas the most frequently isolated microorganism (n = 58, and 10 MRSA), followed by CoNS (n = 35). Overall, 77.7% of patients evolved satisfactorily. Five patients discontinued treatment due to AE (urticaria, cholestasis, increased CPK and rhabdomyolysis). Infection-related mortality was 7.4%. Daptomycin was correctly selected in 94.3% patients, length of therapy was adequate in 87.4%. However, only 47.1% of patients received adequate dosage (underdosing in 27.8%) and in 9.8% of patients, the treatment was not adjusted according to microbiological results. The prevalence of daptomycin use was 3.7 patients/1,000 admissions. Conclusion Daptomycin is often prescribed empirically, using nonadequate dosages and duration of therapy needs also an improvement. The follow-up of patients treated with daptomycin should be considered a priority intervention within an Antimicrobial Stewardship Program. Disclosures All authors: No reported disclosures.

Background Influenza is a potential inducer of acute cardiac events. However, the incidence of influenza in patients admitted to a C-ICU, the accuracy of clinical suspicion and the compliance of influenza vaccination of high-risk patients, are not well known. Objectives: To evaluate the incidence of influenza at C-ICU admission during influenza season, the potential underdiagnosis and the vaccination rate. Methods Prospective study at a tertiary institution including all patients admitted to a C-ICU during 2017–2018 flu season. A nasopharyngeal swab was collected at admission from all patients who consented (198/201, 98.5%) and tested using Xpert® Flu/RSV assay. Clinical data were registered. Results Influenza was detected in 14/198 (7.1%) patients (11 FluA, 3 FluB) and initially suspected by the cardiologist in 57.1% cases. When compared with patients without influenza, flu-positive patients had more respiratory (21.4% vs. 6.0%, P = 0.03) or neurologic diseases (21.4% vs. 4.3%, P < 0.01), contact with relatives with flu-like illnesses (35.7% vs. 14.4%, P = 0.03), antimicrobials use (71.4% vs. 36.4%, P = 0.01) and need for mechanical ventilation (28.6% vs. 3.3%, P < 0.01). Reasons for C-ICU admission between both groups were similar. All patients promptly received oseltamivir and no patient with flu died (0 vs. 3.8%, P = 0.46) despite a high rate of severe presentations (85.7%) and related complications (78.6%). Seasonal flu vaccination was received by 44.9% of the patients admitted to the C-ICU and 52.0% of patients who had indication for flu vaccination. The incidence of influenza in the vaccinated and non-vaccinated population (with flu vaccine indication) was, respectively 12.6% vs. 4.1% (P = 0.08). Flu episodes in vaccinated patients required less mechanical ventilation (20% vs. 75%, P = 0.05) and showed a trend toward shorter length of in-hospital stay (6 vs. 15d, NS). Risks factors for no vaccination despite indication were: younger age (67 vs. 75y-o, P < 0.05) and less comorbidity (Charlson index 4 vs. 5, P < 0.01). Conclusion Seven percent of patients admitted to the C-ICU had influenza, only half of the influenza cases diagnosed were suspected at admission and only half of the patients with indication for flu vaccination, received the vaccine. A clinical score to recognize influenza in these patients is needed. Disclosures All authors: No reported disclosures.

The clinical value of information provided by the Microbiology Laboratory may be reduced by the time it takes to generate results for healthcare providers. The aim of this study was to measure the clinical and economic impact associated with rapid reporting of microbiological results.574 hospitalized patients with a bacterial clinical infection confirmed by culture were evaluated. 284 hospitalized patients were included in the historical control group (results available the day following the analysis) and 290 in the intervention group (results available the same day of the analysis). The Vitek(®) 2 system (bioMérieux) was used for identification and antimicrobial susceptibility testing in both groups.Faster reporting of microbiological results enabled the clinician to optimize the antibiotic treatment sooner (P0.001). This reduction in turnaround time (17.6 h) was associated with improved clinical outcome, a significant reduction in the length of hospitalization and the number of microbiological and biochemical tests performed. Intubation requirements were significantly lower in the intervention group. Mortality rates did not differ significantly between the two groups. Costs incurred for patients in the intervention group were significantly lower than those in the control group, including costs for Microbiology Laboratory testing, antibiotic costs, length of hospitalization and other patient care costs.Rapid microbiological information was associated with quality improvement seen in earlier changes in antibiotic use, an improved clinical outcome and financial benefits.

Opportunistic infection with Pneumocystis jiroveci pneumonia (PCP) has not been recognized as a significant complication of early-stage breast cancer treatment. However, we have observed an increase in PCP incidence among patients receiving chemotherapy for early-stage breast cancer. Herein we identify risk factors for and calculate incidence of PCP in this population. We identified all cases of PCP at Dana–Farber Cancer Institute/Brigham and Women’s Hospital (DFCI/BWH) from 1/1/2000 to 12/31/2013 in patients with stage I–III breast cancer treated with an adriamycin/cyclophosphamide (AC)-containing regimen. Nineteen cases of PCP in non-metastatic breast cancer patients were identified. All patients with PCP were diagnosed after receipt of either three or four cycles of AC chemotherapy on a dose-dense schedule. Patients who developed PCP were treated with median 16.4 mg prednisone equivalents/day as nausea prophylaxis for a median 64 days. The overall incidence of PCP among 2057 patients treated with neoadjuvant or adjuvant dose-dense AC for three or more cycles was 0.6 % (95 % confidence interval 0.3–1.0 %). No PCP was diagnosed in 1001 patients treated with non-dose-dense AC. There was one death from PCP. Women receiving dose-dense AC chemotherapy for early-stage breast cancer are at risk for PCP. Administering the same chemotherapy and corticosteroid dose over an 8-week versus 12-week non-dose-dense schedule appears to have created a novel infectious vulnerability. Replacing dexamethasone with alternative anti-emetics may mitigate this risk.

Carbapenems are recommended for treatment of Enterobacter infections with AmpC phenotypes. Although isolates are typically susceptible to cefepime in vitro, there are few data supporting its clinical efficacy.We reviewed all cases of Enterobacter species bacteremia at 2 academic hospitals from 2005 to 2011. Outcomes of interest were (1) persistent bacteremia ≥1 calendar day and (2) in-hospital mortality. We fit logistic regression models, adjusting for clinical risk factors and Pitt bacteremia score and performed propensity score analyses to compare the efficacy of cefepime and carbapenems.Three hundred sixty-eight patients experienced Enterobacter species bacteremia and received at least 1 antimicrobial agent, of whom 52 (14%) died during hospitalization. Median age was 59 years; 19% were neutropenic, and 22% were in an intensive care unit on the day of bacteremia. Twenty-nine (11%) patients had persistent bacteremia for ≥1 day after antibacterial initiation. None of the 36 patients who received single-agent cefepime (0%) had persistent bacteremia, as opposed to 4 of 16 (25%) of those who received single-agent carbapenem (P.01). In multivariable models, there was no association between carbapenem use and persistent bacteremia (adjusted odds ratio [aOR], 1.52; 95% CI, .58-3.98; P = .39), and a nonsignificant lower odds ratio with cefepime use (aOR, 0.52; 95% CI, .19-1.40; P = .19). In-hospital mortality was similar for use of cefepime and carbapenems in adjusted regression models and propensity-score matched analyses.Cefepime has a similar efficacy as carbapenems for the treatment of Enterobacter species bacteremia. Its use should be further explored as a carbapenem-sparing agent in this clinical scenario.

CD57+T cells increase in several viral infections like cytomegalovirus, herpesvirus, parvovirus, HIV and hepatitis C virus and are associated with several clinical conditions related to immune dysfunction and ageing. We report for the first time an expansion of CD8+CD57+T cells in a young patient with an acute infection with Toxoplasma gondii. Our report supports the concept that CD8+CD57+T cells could be important in the control of chronic phase of intracellular microorganisms and that the high numbers of these cells may reflect the continuing survey of the immune system, searching for parasite proliferation in the tissues.

Hematopoietic stem cell transplantation (HSCT) recipients are at risk for varicella-zoster virus (VZV) reactivation. Vaccination may help restore VZV immunity; however, the available live attenuated VZV vaccine (Zostavax) is contraindicated in immunocompromised hosts. We report our experience with using a single dose of VZV vaccine in 110 adult autologous and allogeneic HSCT recipients who were about 2 years after transplantation, free of graft-versus-host disease, and not receiving immunosuppression. One hundred eight vaccine recipients (98.2%) had no clinically apparent adverse events with a median follow-up period of 9.5 months (interquartile range, 6 to 16; range, 2 to 28). Two vaccine recipients (1.8%) developed a skin rash (one zoster-like rash with associated pain, one varicella-like) within 42 days post-vaccination that resolved with antiviral therapy. We could not confirm if these rashes were due to vaccine (Oka) or wild-type VZV. No other possible cases of VZV reactivation have occurred with about 1178 months of follow-up. Live attenuated zoster vaccine appears generally safe in this population when vaccinated as noted; the overall vaccination risk needs to be weighed against the risk of wild-type VZV disease in this high-risk population.

Mendelsohn and Larrick have recently discussed in a recent article in Rejuvenation Research that dietary modifications of the gut microbiota affect the risk for cardiovascular disease. In this context, dietary patterns and single specific nutrients appear to produce singular consequences on the gut microbiota, subsequently impacting on maintenance of well-being and disease onset or evolution, whose intimate influences and mechanisms are now starting to be disentangled. Thus, the consumption of dietary fiber and particular polysaccharides affects colonic fermentation processes involving short-chain fatty acid production, accompanying changes in the environmental pH, inhibiting Bacteroides spp., and rising levels of butyrate-producing Gram-positive bacteria. This scenario may contribute to the design of novel therapeutic approaches to manipulate gut microbiota to treat cardiovascular diseases and obesity. Indeed, cardiovascular risk may be indirectly dependent on pathways associated with microbe-induced obesity or diabetes through inflammation. Diverse components of the diet, including bioactive molecules with bactericidal functions, such as polyphenols, may play a role on intestinal mucosa inflammation and permeability and contribute to explaining the mutual interactions between obesity, diabetes, and adverse cardiovascular events.

Inappropriate antibiotic prescriptions are associated with an increase in healthcare costs and a decrease in the quality of care. The aim of this study was to measure the clinical and economic impact of rapid microbiological reporting on the specimens most frequently processed by the Microbiology Laboratory. The Vitek® 2 system (bioMerieux) was used for identification and susceptibility testing. Only hospitalized patients with bacterial infections were included. Two groups were established, a historical control group (results available the day following the analysis) and an intervention group (results available the same day of the analysis). Specimens studied and the median length of time from the introduction of the microorganism in the Vitek® 2 until microbiological report were as follows: wound and abscess (control = 23.5 h, intervention = 9.5 h, p