Search

Background Immune-based therapies are standard-of-care treatment for coronavirus disease 2019 (COVID-19) patients requiring hospitalization. However, safety concerns related to the potential risk of secondary infections may limit their use. Methods We searched OVID Medline, Ovid EMBASE, SCOPUS, Cochrane Library, clinicaltrials.gov, and PROSPERO in October 2020 and updated the search in November 2021. We included randomized controlled trials (RCTs). Pairs of reviewers screened abstracts and full studies and extracted data in an independent manner. We used RevMan to conduct a meta-analysis using random-effects models to calculate the pooled risk ratio (RR) and 95% CI for the incidence of infection. Statistical heterogeneity was determined using the I2 statistic. We assessed risk of bias for all studies and rated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology. We conducted a meta-regression using the R package to meta-explore whether age, sex, and invasive mechanical ventilation modified risk of infection with immune-based therapies. The protocol is registered with PROSPERO (CRD42021229406). Results This was a meta-analysis of 37 RCTs including 32 621 participants (mean age, 60 years; 64% male). The use of immune-based therapy for COVID-19 conferred mild protection for the occurrence of secondary infections (711/15 721, 4.5%, vs 616/16 900, 3.6%; RR, 0.82; 95% CI, 0.71–0.95; P = .008; I2 = 28%). A subgroup analysis did not identify any subgroup effect by type of immune-based therapies (P = .85). A meta-regression revealed no impact of age, sex, or mechanical ventilation on the effect of immune-based therapies on risk of infection. Conclusions We identified moderate-certainty evidence that the use of immune-based therapies in COVID-19 requiring hospitalization does not increase the risk of secondary infections.

Background Cytomegalovirus (CMV) seronegative solid organ transplant (SOT) recipients who receive grafts from seropositive donors are at high risk of CMV disease. Antiviral prophylaxis in usually given to this group of patients to prevent illness. Patients are still at risk of CMV after completion of prophylaxis. Surveillance after prophylaxis is used in some centres to prevent late CMV disease, but there is scant information of its efficacy. Finally, little is known on CMV kinetics post-prophylaxis in high-risk patients. Methods This was a retrospective cohort study including adult CMV mismatch (D+/R-) SOT recipients between 2003-2017 at a multiorgan transplant center in Canada. Post-prophylaxis CMV kinetics were classified into 3 patterns of DNAemia: no DNAemia, single episode of DNAemia and recurrent episodes of DNAemia. We calculated the cumulative incidence of each DNAemia pattern. We also compared 5-year mortality according to CMV DNAemia pattern by Cox-regression analysis. Patients were monitored weekly with CMV viral load for 12 weeks after completion of prophylaxis. Results Two-hundred and forty-five transplant patients were included (Table 1). Median follow up time was 9.2 years (7-12.7). Death occurred in 32 patients during the study period, the median time to death was 7.3 years (4.9-10). Pattern 1 (no CMV DNAemia) occurred in 38%, 27% had a single episode (pattern 2) of CMV DNAemia and 35% had recurrent (pattern 3) CMV DNAemia. Median time to DNAemia was 186 days. The first episode occurred at a significantly shorter interval in liver recipients when compared to non-liver recipients, 158 days (134-217) vs. 208 days (149-315), p=0.0164. Recurrent CMV DNAemia (pattern 3) was significantly more common in lung transplant recipients compared to non-lung transplant recipients. (63% vs. 32% p=0.003). Mortality at 5 years was statistically not different between CMV patterns, adjusted by organ transplanted and age (Pattern 1 reference; pattern 2 HR 1.484 [0.24-9. Table 1.Population characteristics.* Includes 16 simultaneous kidney-pancreas, pancreas after kidney or pancreas alone, 1 combined liver-kidney, 1 multivisceral. ATG: Anti-thymocyte globulin. Conclusion A surveillanceafter prophylaxis strategy allowed us to characterize the CMV kinetics post-prophylaxis, with 35% of CMV mismatch patients having recurrent CMV episodes. CMV kinetic pattern was not associated with 5 years mortality in CMV high-risk patients. Disclosures Carlos Cervera, Associate Professor, Astra-Zeneca: Advisor/Consultant|AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Sunovion: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Honoraria|VerityPharma: Advisor/Consultant.

Background Therapeutic drug monitor (TDM) guided optimized dosing of Voriconazole allows optimal drug exposure in the management of mold infection (MI). In addition to already known nuances in pharmacokinetics such as CYP2C19 genetic polymorphism and the role of drug interactions both necessitating TDM, case reports have suggested that auto-induction may occur after initially achieving a therapeutic level. We assessed whether the levels of Voriconazole can change over time and become subtherapeutic due to auto-induction. Methods We prospectively enrolled, adults ≥ 18 y.o of age, on Voriconazole for the treatment of MI at the University Of Alberta Hospital. After achieving an initial therapeutic margin, (1–5.5mg/l), we monitored Voriconazole levels twice a month, using high-performance liquid chromatography, until discontinuation or at 12 weeks of therapy. We calculated the incidence of Voriconazole sub-therapeutic concentrations (auto-induction) defined as drop of Voriconazole level below one, with previous concentrations between the therapeutic margins of 1–5.5 mg/L. Adjustment of Voriconazole dosing in case of auto-induction was at the discretion of the treating physician. The excess Voriconazole dose adjustment was calculated in patients where dosing was increased. Results Between January 2021 and April 2022, we enrolled 12 patients. Median age (IQR) was 62 (52–73), and 25 % were female. Patient characteristics are in table 1. Auto-induction was observed in 6/10 (60%) who completed 12 weeks follow up blood work. Median time to auto-induction was of 46 days (39–55). Voriconazole dosing was increased in 4/6 patients with auto-induction. Of the four patients with dose adjustment, the cumulative Voriconazole dose was 13% higher than expected, which correspond to 5,300 mg excess Voriconazole per patient to maintain therapeutic levels. Conclusion Auto-induction is common in patients treated with Voriconazole. Future studies are needed to assess if undetected auto-induction affects outcomes. Funding: AVIR Pharma. Disclosures Carlos Cervera, Associate Professor, Astra-Zeneca: Advisor/Consultant|AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Sunovion: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Honoraria|VerityPharma: Advisor/Consultant Dima Kabbani, MD, MSc, AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|GSK: Honoraria|Merck: Grant/Research Support.

Background Colonization with multi-drug resistant bacteria (MDR) in solid organ transplant (SOT) recipients increases the risk of post-transplant bacterial infection. MDR colonization impact on graft survival and mortality is not well established. Methods A search was executed by an expert librarian on PROSPERO, OVID Medline, Ovid EMBASE, Wiley Cochrane Library, ProQuest dissertations and Theses Global and SCOPUS, from inception until October 26, 2021. Adult SOT colonized with Methicillin resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE), Extended-spectrum beta-lactamase (ESBL) or AmpC producing bacteria, carbapenem resistant Enterobacteriaceae (CRE), or MDR Pseudomonas were included and compared to non-colonized SOT. Pairs of reviewers screened abstracts and full studies for inclusion, and extracted data independently. We used RevMan to conduct a meta-analysis using random effects models to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) for the incidence of infection, mortality, and graft failure. Statistical heterogeneity was determined using the I2 statistic. Figure-1 PRISMA chart, systemic review and metanalysis on Impact Of Colonization By Multi Drug Resistant Bacteria on Graft Survival, Risk of Infection, and Mortality in Recipients of Solid Organ Transplant. Results 59 articles spanning from 1989 to 2021 were included (Figure-1). Liver transplant (43 studies) and VRE colonization (17 studies) were the most common organ and MDR pathogen. MDR surveillance was performed by culture (71%) and PCR (6.7%). In liver transplant recipients, VRE and MRSA colonization were associated with increased infection risk, but not mortality (VRE infection: RR= 2.40 (95%CI 1.54-3.73; p< 0.001), I2= 66%; VRE mortality: RR= 1.64 (95%CI 0.88-3.05; p=0.12), I2= 44%; MRSA infection: RR= 4.07 (95%CI 2.66-6.24; p< 0.001), I2= 59%; MRSA mortality RR=1.47 (95%CI 0.79-2.76; p=0.23), I2= 35%). ESBL and CRE colonization were associated with increased risk of infection (ESBL: RR=9.87 (6.12-15.93); p< 0.001), I2=13%; CRE: RR= 13.64 (95%CI 5.73-32.47); p< 0.001), I2= 66%). CRE colonization was associated with increased mortality, RR=5.79 (95% CI 1.80-18.63; p=0.003), I2=0%. Conclusion While colonization with MRSA and VRE in liver transplant was not associated with increase mortality, CRE colonization was associated with almost 6-fold increased risk of death. These data should be taken into account when stratifying the risk of transplant. Disclosures Carlos Cervera, Associate Professor, Astra-Zeneca: Advisor/Consultant|AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Sunovion: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Honoraria|VerityPharma: Advisor/Consultant Dima Kabbani, MD, MSc, AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|GSK: Honoraria|Merck: Grant/Research Support.

Objectives Ceftolozane/tazobactam is a cephalosporin/β-lactamase inhibitor combination with activity against Gram-negative bacilli. We report the use of ceftolozane/tazobactam in Canada using a national registry. Methods The CLEAR registry uses REDCapTM (Research Electronic Data Capture) (online survey, https://is.gd/CLEAR_ceftolozanetazobactam) to capture details associated with clinical use of ceftolozane/tazobactam. Results Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone/joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin structure infection (7.8%). 17.6% of patients had bacteremia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.7%), or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active versus Gram-negative bacilli in 39.2% of patients (aminoglycosides [15.7%], fluoroquinolones [7.8%] and colistin/polymyxin B [7.8%]). The dosage regimen was customized in all patients based on their creatinine clearance. Treatment duration was primarily >10 days (60.8% of patients) with microbiological success in 60.5% and clinical success in 64.4% of patients. 7.8% of patients had adverse effects not requiring drug discontinuation. Conclusions In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused MDR P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates, and an excellent safety profile.

We present the case of a 66-year-old female with a history of renal transplant in 1999 with new onset fevers and diffuse skin ulcerations. In this article, we present the diagnostic studies, differential diagnosis, and treatment decisions for the case.

Background Enterococcal bacteraemia (EB) is common, particularly in the nosocomial setting, and its management poses a challenge for clinicians and microbiologists. Objectives The aim was to summarize the more relevant features of EB and to provide a practical state-of-the-art on the topics that more directly affect its management. Sources Pubmed articles from inception to 31 May 2020. Content The following topics are covered: epidemiological, clinical and microbiological characteristics and factors associated with prognosis of EB; diagnosis and work-up, including the use of echocardiography to rule out endocarditis; antibiotic management with special focus on antimicrobial resistance and complicated EB; and the role of infectious disease consultation and the use of bundles in EB. In addition, three clinical vignettes are presented to illustrate the practical application of the guidance provided, and major gaps in the current evidence supporting EB management are discussed. Implications EB is associated with large burdens of morbidity and mortality, particularly among fragile and immunosuppressed patients presenting complicated bacteraemia due to multidrug-resistant enterococci. Most cases of EB are caused by Enterococcus faecalis, followed by E. faecium. EB often presents as polymicrobial bacteraemia. Rapidly identifying patients at risk of EB is crucial for timely application of diagnostic techniques and empiric therapy. Early alert systems and rapid diagnostic techniques, such as matrix-assisted desorption ionization–time of flight mass spectrometry, especially if used together with infectious disease consultation within bundles, appear to improve management and prognosis of EB. Echocardiography is also key in the work-up of EB and should probably be more extensively used, although its exact indications in EB are still debated. Multidisciplinary approaches are warranted due to the complexity and severity of EB.

Previous studies have frequently reported effects of abiotic factors on herbivore‐induced plant defences based on effects on single plant traits. However, plants commonly express multiple defences simultaneously and these traits are often correlated. Thus, a fuller understanding of abiotic‐context dependency in plant defence requires measuring multiple traits and addressing their patterns of correlated expression. We evaluated the effects of soil salinity on the expression of direct (phenolic compounds, gossypol gland density) and indirect (volatile organic compounds, extrafloral nectar) defensive traits in wild cotton Gossypium hirsutum. Specifically, we asked whether soil salinity affects the induction of these traits, and whether it shapes trait correlations potentially underlying altered patterns of trait induction. We conducted a factorial experiment with 16 cotton genotypes where we manipulated soil salinity and defence induction by applying artificial leaf damage (25% mechanical damage and caterpillar oral secretions) and measured defence levels at different time points post damage. Leaf damage induced most traits except gossypol gland density, whereas salinity did not have a mean effect (across constitutive and induced levels) on any of the measured traits. Nonetheless, salinity prevented the induction of phenolic compounds (condensed and hydrolysable tannins), and also affected trait correlations. Specifically, phenolic compounds were negatively associated with nectar production only under salinized conditions, an apparent trade‐off that could affect the induction of phenolic compounds. In addition, positive correlations between phenolic compounds and gland density and root biomass observed under control conditions were lost under salinized conditions. Synthesis. By investigating the effects of soil salinity on the expression of multiple direct and indirect defensive traits and their underlying correlations, these findings build towards a better understanding of how abiotic context dependency shapes plant allocation to and expression of multiple defensive traits.

Background Cytomegalovirus (CMV) is the most common opportunistic pathogen, following solid organ transplantation (SOT), that leads to direct and indirect effects. The aim of this study was to assess the impact of CMV exposure at transplantation on the rate of posttransplant thrombotic events (TEs). Methods We conducted a retrospective cohort study of patients transplanted at the University of Alberta Hospital between July 2005 and January 2018. We included adult SOT CMV-seronegative recipients at transplantation who received an allograft from either a seropositive donor (D+/R-) or a seronegative donor (D-/R-). Results A total of 392 SOT recipients were included: 151 (39%) liver, 188 (48%) kidney, 45 (11%) pancreas, and 8 (2%) other transplants. The mean age was 47 years, 297 (76%) were males, and 181 (46%) had a CMV D+/R- donor. Patients in the CMV D+/R- cohort were slightly older (51 years versus 48 years in the D-/R- cohort; P = .036), while other variables, including cardiovascular risk factors and pretransplant TEs, were not different between groups. Overall, TEs occurred in 35 (19%) patients in the CMV D+/R- group, versus 21 (10%) in the CMV D-/R- group, at 5 years of follow-up (P = .008); the incidence rates per 100 transplant months were 5.12 and 1.02 in the CMV D+/R- and CMV D-/R- groups, respectively (P = .003). After adjusting for potential confounders with a Cox regression model, a CMV D+/R- transplantation was independently associated with an increased risk of a TE over 5 years (adjusted hazard ratio, 3.027; 95% confidence interval, 1.669–5.488). Conclusions A CMV D+/R- transplantation is associated with an increased risk of a TE posttransplantation.

We report the effect of prospective audit and feedback (PAF) on inpatient fluoroquinolone (FQN) prescriptions. During the PAF period, FQN use decreased from 39.19 to 29.58 days of therapy per 1,000 patient days (P < .001) and appropriateness improved from 68% to 88% (P < .001). High-yield indications to target included noninfectious urinary tract and respiratory presentations.

Introduction: Vancomycin-resistant enterococci (VRE) colonization and subsequent infection results in increased morbidity, mortality and use of health-care resources. The burden of VRE colonization in liver transplant candidates and recipients is significant. VRE colonization is a marker of gut dysbiosis and its impact on the microbiota-liver axis, may negatively affect graft function and result in negative outcomes pre- and post-transplantation. Areas covered: In this article we describe the epidemiology of VRE colonization, risk factors for VRE infection, health-care costs associated with VRE, with a focus on the impact of VRE colonization on liver transplant recipients' fecal microbiota, the therapeutic strategies for VRE decolonization and proposed pathophysiologic mechanisms of VRE colonization in liver transplant recipients. Expert opinion: VRE colonization results in a significant loss of bacterial microbiome diversity. This may have metabolic consequences, with low production of short-chain fatty acids which may, in turn, result in immune dysregulation. As antibiotics have failed to decolonize the gut, alternative strategies such as fecal microbiota transplantation (FMT), stimulation of intestinal antimicrobial peptides and phage therapy warrants future studies.

Background Refractory or resistant (R/R) cytomegalovirus (CMV) infection after hematopoietic cell transplant (HCT) and solid organ transplant (SOT) cause serious, potentially fatal complications; therapeutic options are limited. In a Phase 3 study (NCT02931539), maribavir (MBV) was superior to investigator-assigned therapy (IAT; val/ganciclovir, foscarnet, cidofovir) for CMV clearance (Wk 8) and clearance plus symptom control (Wk 8 through Wk 16) in HCT/SOT recipients with R/R CMV infections. Here we present further study results on efficacy and safety of MBV in the rescue arm. Methods Patients (pts) were stratified and randomized 2:1 to MBV (400 mg/bid) or IAT for 8-wk treatment then 12-wk follow-up. After minimum 3 wks’ treatment, pts in the IAT group meeting criteria (worsening/lack of improvement of CMV infection or failure to achieve viremia clearance plus IAT intolerance) could enter a MBV rescue arm (8-wk treatment, 12-wk follow-up). In the rescue arm, efficacy was evaluated by confirmed CMV viremia clearance (plasma CMV DNA < 137 IU/mL in 2 consecutive tests ≥ 5 days apart) at end of Wk 8 and confirmed clearance with symptom control at Wk 8 through Wk 16. Safety was assessed. Results A total of 352 pts were randomized (MBV: 235, IAT: 117, randomized set). Confirmed CMV viremia clearance at Wk 8 was achieved in 131 (55.7%) and 28 (23.9%) pts, respectively, in the randomized set. Having met criteria, 22 (18.8%) pts entered the MBV rescue arm; at entry, 6 (27.3%) pts had developed neutropenia and 9 (40.9%) had increased serum creatinine (Table 1). At Wk 8 of rescue therapy, 11 (50.0%) pts achieved confirmed CMV viremia clearance; 6 (27.3%) pts had CMV clearance with symptom control at Wk 8 maintained through Wk 16 (Table 2). All 22 pts reported treatment-emergent adverse events (TEAEs; Table 3); most common TEAEs of special interest were nausea, vomiting, and diarrhea (54.5%), and taste disturbance (50.0%). Neutropenia and acute kidney injury TEAEs were reported by 0 and 3 pts in the rescue arm, respectively. Table 1. Summary of patients from IAT-randomized group meeting criteria for entry into MBV rescue arm* Table 2. Patients achieving confirmed CMV viremia clearance at end of Wk 8 (end of treatment) or achieving confirmed CMV viremia clearance and symptom control at end of Wk 8 maintained through Wk 16 Table 3. Treatment-emergent adverse events during the on-rescue observation period Conclusion Rescue arm data show MBV was efficacious for R/R CMV infection in HCT/SOT recipients inadequately responding to IAT with/without intolerance and had a similar safety profile to that reported for pts in the randomized MBV group. Disclosures Marcus Pereira, MD, Hologic (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)Takeda (Scientific Research Study Investigator, Advisor or Review Panel member) Carlos Cervera, MD, PhD, Avir Pharma (Consultant, Advisor or Review Panel member)Lilly (Consultant, Advisor or Review Panel member)Merck (Consultant, Advisor or Review Panel member, Research Grant or Support)Sunovion (Consultant, Advisor or Review Panel member)Takeda (Consultant, Advisor or Review Panel member)Veritas Pharma (Consultant, Advisor or Review Panel member) Camille Kotton, MD, Shire/Takeda (Advisor or Review Panel member) Camille Kotton, MD, UpToDate (Individual(s) Involved: Self): I write chapters on zoonoses for UpToDate., Independent Contractor Joseph Sasadeusz, MBBS, PhD, Abbvie (Grant/Research Support, Other Financial or Material Support, Consulting fee: speaker)Gilead (Other Financial or Material Support, Speaker)Merck (Grant/Research Support, Consulting fee: speaker)Takeda (Grant/Research Support) Jingyang Wu, MS, Shire Human Genetic Therapies, Inc., a Takeda company (Employee, Other Financial or Material Support, Holds stock/stock options) Martha Fournier, MD, Shire Human Genetic Therapies, Inc., a Takeda company (Employee, Other Financial or Material Support, Holds stock/stock options)Shire ViroPharma, a Takeda company (Other Financial or Material Support, This study was funded by Shire ViroPharma, a Takeda company)

Introduction: Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts. Risk factors for Pneumocystis jirovecii pneumonia (PJP) include HIV, organ transplant, malignancy, certain inflammatory or rheumatologic conditions, and associated therapies and conditions that result in cell-mediated immune deficiency. Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue. First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole (TMP-SMX), though intolerance or allergy, and rarely treatment failure, may necessitate alternate therapeutics, such as dapsone, pentamidine, atovaquone, clindamycin, primaquine and most recently, echinocandins as adjunctive therapy. In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit.Areas covered: This review article covers the epidemiology, pathophysiology, diagnosis, microbiology, prophylaxis indications, prophylactic therapies, and treatments.Expert opinion: TMP-SMX has been first-line therapy for treating and preventing pneumocystis for decades. However, its adverse effects are not uncommon, particularly during treatment. Second-line therapies may be better tolerated, but often sacrifice efficacy. Echinocandins show some promise for new combination therapies; however, further studies are needed to define optimal antimicrobial therapy for PJP as well as the role of corticosteroids in those without HIV.

Background HHV-8/Kaposi Sarcoma herpesvirus has been associated with a broad spectrum of diseases in solid organ transplant (SOT) recipients. Primary donor-derived infection can be associated with severe and rapidly fatal non-neoplastic disease, and diagnosis is made with high HHV-8 DNAemia. Methods We carried out an international survey to investigate the current approach to HHV-8 screening, and management in SOT since a protocol has not been established by international guidelines. Results A total of 51 transplant centers from 15 countries filled out the survey. HHV-8-associated diseases in SOT have been diagnosed during the previous 5 years in 67% of centers. Pretransplant serological screening is performed in 17 centers (33%), and posttransplant HHV-8 nucleic acid testing (NAT) monitoring is performed in 21 centers (41%). Performing HHV-8 NAT monitoring and serological screening were found associated with having diagnosed in the previous 5 years a non-malignant HHV-8-associated disease. Conclusions Serological pretransplant screening of donors and recipients and post-transplant HHV-8 NAT monitoring recommendations should be standardized. Even though serological assays are not optimal, they could contribute to increasing knowledge on epidemiology and management of HHV-8-associated diseases after SOT.

Data on geographic distribution and life cycles of parasitic nematodes of the genus Anisakis in tropical oceanic regions are extremely scarce. Myctophids (lantern fishes) are a key component of mesopelagic trophic webs and could play a significant role in the transmission of Anisakis spp. in these regions. We examined Anisakis infections in a sample of 160 myctophids collected in three localities from the Indian Exclusive Economic Zone (Arabian Sea) in 2015–16. Due to the poor condition of fish, a combination of morphological data and molecular barcoding was used to identify myctophids. Of the 104 specimens that could be identified at least to genus level, 75 (72.1%) were assigned to Diaphus spp. A total of 131 Anisakis larvae were collected from the fish sample (prevalence: 52.5%). One larva was identified as type I, 114 as type II, and 16 larvae could not be assigned to either type. The morphology of all type II larvae conformed to the recent diagnosis of Anisakis brevispiculata. DNA could be obtained only from four larvae, and phylogenetic analyses based on mtDNAcox2 confirmed the identification. Anisakis brevispiculata is specific to dwarf and pygmy sperm whales (Kogiidae), which feed on mesopelagic cephalopods and marginally on myctophids. Therefore, myctophids could play a dual role in the transmission of A. brevispiculata, as direct prey of kogiids and/or as prey of cephalopods that consume myctophids. The prevalence of A. brevispiculata varied significantly in myctophid samples that were just ~ 265 km apart, suggesting potential local effects on transmission rates.

Direct-acting antivirals have proved to be highly efficacious and safe in monoinfected liver transplant (LT) recipients who experience recurrence of hepatitis C virus (HCV) infection. However, there is a lack of data on effectiveness and tolerability of these regimens in HCV/HIV-coinfected patients who experience recurrence of HCV infection after LT. In this prospective, multicenter cohort study, the outcomes of 47 HCV/HIV-coinfected LT patients who received DAA therapy (with or without ribavirin [RBV]) were compared with those of a matched cohort of 148 HCV-monoinfected LT recipients who received similar treatment. Baseline characteristics were similar in both groups. HCV/HIV-coinfected patients had a median (IQR) CD4 T-cell count of 366 (256-467) cells/mu L. HIV-RNA was

espanolEs importante estudiar la actividad de forrajeo de Polistinae para entender mejor su impacto en los ecosistemas. En este trabajo se describe la actividad de un nido en fase de post-emergencia de Polybia diguetanaen relacion a la temperatura y humedad relativa. El area de estudio fue un campus universitario en Merida, Mexico, con clima calido subhumedo. Se muestreo en las siguientes fechas de 2019: enero 30 y 31, febrero 5 y 6, y abril 9 y 10, el 9 llovio de 9:00 a 11:45 horas. Se tomo un video del nido de 3:40 min de duracion cada media hora, iniciando a las 7:30 y finalizando a las 14:45 horas. En total fueronfilmados 83 videos con una duracion acumulada de 308,5 minutos. Se midio la temperatura (°C) y humedad relativa a tres metros del nido al iniciar cada video. Se realizaron analisis de correlacion parcial con temperatura y humedad como variables independientes y frecuencias de despegues y aterrizajes como dependientes, el 9 de abril se excluyo del analisis por el posible efecto de la lluvia. En el dia lluvioso los aterrizajes y despegues fueron mas frecuentes a las 7:30 que hubo la temperatura mas alta y lahumedad relativa mas baja; en los otros dias los despegues fueron mas frecuentes a las 11:00 y los aterrizajes a las 14:00. La temperatura se correlaciono positivamente tanto con los despegues (r=0,21, p=0,05) como con los aterrizajes (r =0,44, p EnglishIt is important to study the foraging activity of Polistinae in order to understand their impact on ecosystems. In this work we describe the activity of one nest in post-emergence state of Polybia diguetanain relation to temperature and relative humidity. The study area is a university campus in Merida, Mexico, with warm sub -humid climate. Sampling were taken in the following dates of 2019: January 30 and 31, February 5 and 6 and April 9 and 10, the 9 it rained from 9:00 to 11:45 hours. A video lasting 3:40 min was taken every half an hour, beginning at 7:30 and finishing at 14:45. Eighty-three videos were recorded with an accumulated time of 308.5 minutes. When the video recording was beginning, temperature (°C) and relative humidity (%) were measured at a distance of 3 meters from the nest. Partial correlation analysis were carried out, with temperature and relative humidity as independent variables and wasp departures and arrivals frequencies as response variables, April 9th was excluded from this analysis for excluding the effect of the rain. In the rainy days the highest frequency of arrivals and departures was at 7:30, when the temperature was the highest and the humidity the lowest. In other days departure frequency was higher at 11:00 and arrivals at 14:00. Temperature was positively correlated to departures (r=0.21, p=0.05) and arrivals (r= 0.44, p

FOSIMI Investigators., This work was supported by the Ministerio de Sanidad y Consumo of Spain (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain, Grant #EC0800190). JMP received a “Rio Hortega” Research Grant (CM14/00135; 2015-16) from Instituto de Salud Carlos III and the Ministerio de Economia and Competitividad, Madrid (Spain) and the ESCMID/FEMS Research Fellowship 2016. JMM received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–19.

Background The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies. Aims To review, from an infectious diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3–targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors, and to suggest preventive recommendations. Sources Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. Content T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death (PD)-1/PD-1 ligand 1 (PD-L1)-targeted agents do not appear to intrinsically increase the risk of infection but can induce immune-related adverse effects requiring additional immunosuppression. Although CD4+ T-cell lymphopenia is associated with alefacept, no opportunistic infections have been observed. Progressive multifocal leukoencephalopathy (PML) may occur during therapy with natalizumab (anti–α4-integrin monoclonal antibody (mAb)) and efalizumab (anti-CD11a mAb), but no cases have been reported to date with vedolizumab (anti-α4β7 mAb). In patients at high risk for PML (positive anti-JC polyomavirus serology with serum antibody index >1.5 and duration of therapy ≥48 months), the benefit–risk ratio of continuing natalizumab should be carefully considered. Fingolimod induces profound peripheral blood lymphopenia and increases the risk of varicella zoster virus (VZV) infection. Prophylaxis with (val)acyclovir and VZV vaccination should be considered. Proteasome inhibitors also increase the risk of VZV infection, and antiviral prophylaxis with (val)acyclovir is recommended. Anti-Pneumocystis prophylaxis may be considered in myeloma multiple patients with additional risk factors (i.e. high-dose corticosteroids). Implications Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.

Antecedentes y Objetivos: Agave angustifolia, o chelem, es el único maguey silvestre de la Península de Yucatán y es el ancestro de especies domesticadas de gran valor económico y cultural. Presta importantes servicios ambientales como recurso alimenticio para la fauna, fijación de suelos arenosos y captura de carbono en ambientes áridos con suelos pobres. Es un cultivo potencial de cara al aumento de las sequías predichas para la región y del empobrecimiento genético del henequén. El objetivo de este trabajo es recabar datos sobre la densidad de sus poblaciones, su patrón espacial, estructura poblacional y la relación entre su abundancia y los factores ambientales en el matorral costero de Yucatán, con el fin de evaluar su uso en la restauración ecológica.Métodos: Se muestrearon tres localidades costeras: Chuburná (Ch), San Benito (SB) y Río Lagartos (RL). En SB y RL se trazaron 36 cuadrantes de 4 m2; dentro de cada uno se estimó el porcentaje de cobertura de Agave angustifolia, el de los arbustos de más de 1 m de alto y la cobertura de mantillo. Se tomaron muestras de suelo a las que se analizó pH, conductividad eléctrica, nitrógeno total, materia orgánica e escala de gris. Se describieron la densidad poblacional, distribución espacial y estructura por tamaños de A. angustifolia en SB y Ch.Resultados clave: La cobertura de Agave angustifolia se correlaciona negativamente con la cobertura de arbustos y mantillo, y cantidad de materia orgánica. Las densidades de su población fueron inferiores a 0.1 individuos/m2, hubo una mayor proporción de plántulas y su distribución espacial es agregada.Conclusiones: Al soportar suelos pobres, altas temperaturas y radiación solar, la especie puede servir para restaurar algunas funciones ecológicas en las zonas más áridas de la costa donde la vegetación ha sido severamente dañada.

Purpose Respiratory viral infection (RVI) in lung transplant recipients (LTR) have variably been associated with poor outcomes. Our center uses systemic corticosteroids (orally or intravenous) in some RVI cases to treat inflammation based on clinical judgment, but evidence for this is limited. Methods We reviewed all adult LTR diagnosed with RVI (via nasopharyngeal swab or bronchoscopy) between 2017 and 2019. The primary outcome was recovery of lung function (forced expiratory volume in 1 second [FEV1]) at next stable visit between 1- and 12-months post-infection, expressed as a ratio between stable, representative FEV1 at follow up divided by stable FEV1 prior to infection (FEV1 recovery ratio). We modelled the association between steroid use and FEV1 recovery ratio using linear regression, adjusting for age, sex, transplant type, FEV1 presentation ratio (FEV1 at time of viral infection divided by stable FEV1 prior), hospitalization, coexistent bacterial or fungal infection, time post-transplant and CLAD status at infection. Results 158 patients were diagnosed with RVI, 62 (39%) of whom received corticosteroids. 9 patients (6%) died prior to any follow-up lung function, including two deaths attributed to infection and two to bronchiolitis obliterans. Baseline characteristics were similar between steroid treated and untreated, but steroid-treated patients had a lower FEV1 presentation ratio (0.90 vs. 1.00, p=0.0094) and were more likely to have CLAD at infection (26% vs. 10%, p=0.0268). Mean FEV1 recovery ratio was 1.00 (SD 0.20) with no relationship to specific virus type. Steroid treatment was not associated with FEV1 recovery ratio either unadjusted (p=0.3709) or adjusted (p=0.4498). Conclusion Treatment with systemic corticosteroids was not associated with improved FEV1 recovery in our cohort even after adjustment for presentation severity and other factors. This suggests systemic steroids have limited utility in the management of RVI in this population.

Mycoplasma hominis is part of the genitourinary flora in sexually active people and can cause disseminated infection in immunocompromised patients. We describe a rare case of an immunocompetent pregnant woman with simultaneous necrotizing HSV hepatitis and disseminated M. hominis infection. Detection of M. hominis and antimicrobial susceptibility testing of this fastidious organism in the clinical laboratory is discussed.

BACKGROUND Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients. METHODS We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017. RESULTS A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years. CONCLUSIONS This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.

INTRODUCTION The significance of granuloma in explanted lungs of lung transplant recipients (LTR) on the development of post-transplant mycobacterial infection is unclear. METHODS A retrospective review comparing LTRs and heart-lung transplant (H-LTR) recipients with granuloma in the explanted lungs between 2000 and 2012 (excluding those LTRs with granuloma due to sarcoidosis) and LTRs or H-LTRs without granuloma. Patients were followed for 2 years post-transplant. RESULTS A total of 144 LTRs and 4 H-LTRs with granulomas (75 necrotizing and 73 non-necrotizing) and a comparator cohort of 144 LTRs and 4 H-LTRs without granuloma were analyzed. In LTRs with granulomas, identification of infectious organisms was more common by histopathology (35 AFB and 22 fungal) compared to cultures (six NTM and seven fungal) taken around time of the transplant. LTRs with granulomas were more likely to have pre-transplant non-tuberculous mycobacteria (NTM) infection compared to LTRs without granuloma; P

A 40-year-old female with a history of type 1 diabetes mellitus and solitary pancreas transplant, presented with pancreatic graft rejection 1-year post-transplant. Incidentally, a 1.1 cm right lower lobe cavity was identified during her workup. Given the augmentation of immunosuppression, voriconazole was empirically started for possible invasive pulmonary aspergillosis. As the patient was a painter, this resulted in a significant change in the colors of her paintings. Ultimately, she was diagnosed with pulmonary coccidioidomycosis and her visual disturbances resolved after the voriconazole was changed to fluconazole. Voriconazole causes visual disturbances in 20%-30% of the patients most commonly phototopsias; dyschromatopsias typically involving the tritan axis have also been reported. This case illustrates well the potential impact of voriconazole on spectral sensitivity and color perception.

Background and aims Cirrhosis is associated with dysbiosis, but its functional consequences are still largely unknown. Short-chain fatty acids (SCFAs) account for physiological interactions between the gut microbiota and host. Our aim was to assess the impact of cirrhotic dysbiosis on the production of SCFAs. Methods Seventeen patients with cirrhosis and 17 controls were selected. Microbiota composition in faecal samples was assessed by next-generation 16S rRNA gene sequencing. SCFAs were measured with GC-MS in faecal samples and after in vitro batch fermentations using arabinoxylan, resistant starch, pectin, and lactulose as substrates. Results Among the 17 cirrhotic patients (mean age 58, eight males), six, nine and two were, respectively, Child-Pugh class A, B and C. Eleven patients were on oral antibiotics, 11 on lactulose and 13 on proton pump inhibitors. Cirrhotic patients showed marked differences in the composition and diversity of gut microbiome when compared to controls, that were more pronounced with increased severity. Stool samples from cirrhotic patients showed lower SCFAs content and reduced capacity to produce SCFAs in batch fermentations, with butyrate production being the most abnormal. These functional aberrancies were more pronounced with greater liver disease severity. Abundance of Ruminococcus faecis (in family Ruminococcaceae), Faecalicatena fissicatena and Fusicatenibacter saccharivorans (in family Lachnospiraceae) was positively correlated with the SCFAs production. Conclusion Cirrhotic dysbiosis is associated with a decreased capacity to ferment non-digestible carbohydrates into SCFAs, especially into butyrate. These functional abnormalities are more pronounced as disease progresses. These results might inform the design of gut-targeted therapies for cirrhosis.

Urinary tract infections are common after transplantation and the most frequent infectious complication of kidney transplant recipients. The prevalence of UTI post renal transplantation ranges from 23-85%, but this is less know for other solid organ transplants. Risk factors for UTI are similar to those described in the general population, and usually involves invasive procedures after surgery. The requirement of ureteric stents and post-transplant urinary obstruction are specific risk factors for kidney transplant patients that partially explains the high incidence of UTI in this setting. UTI are classified into lower (cystitis) and upper (pyelonephritis) tract infections according to clinical symptoms. Lower UTI are usually treated with oral antibiotics and usually has minor or absent impact in the allograft. Upper UTI require intravenous antibiotics and hospital admission in most cases and in kidney transplant patients can deteriorate the function of the allograft and patient’s survival. In kidney transplant patients, asymptomatic bacteriuria should only be treated during the first 1-2 months post-transplantation. After this period of time, monitoring urine cultures is controversial and has not shown significant benefits. Some kidney transplant patients develop recurrent UTI which usually worsen the quality of life. To decide antibiotic prophylaxis for recurrent UTI we should take into account the clinical impact of previous UTI, the kidney allograft function, antibiotic sensitivities of previous isolated uropathogens and colonization with multi-drug resistant bacteria.