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Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated with increased mortality rates. The increasing proportion of severely immunocompromised patients with COVID-19 who require mechanical ventilation warrants research into the incidence and impact of CAPA during the vaccination era., Methods: We performed a retrospective, monocentric, observational study. We collected data from adult patients with severe COVID-19 requiring mechanical ventilation who were admitted to the intensive care unit (ICU) of University Hospitals Leuven, a tertiary referral center, between 1 March 2020 and 14 November 2022. Probable or proven CAPA was diagnosed according to the 2020 European Confederation for Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) criteria., Results: We included 335 patients. Bronchoalveolar lavage sampling was performed in 300 (90%), and CAPA was diagnosed in 112 (33%). The incidence of CAPA was 62% (50 of 81 patients) in European Organisation for Research and Treatment of Cancer (EORTC)/Mycosis Study Group Education and Research Consortium (MSGERC) host factor-positive patients, compared with 24% (62 of 254) in host factor-negative patients. The incidence of CAPA was significantly higher in the vaccination era, increasing from 24% (57 of 241) in patients admitted to the ICU before October 2021 to 59% (55 of 94) in those admitted since then. Both EORTC/MSGERC host factors and ICU admission in the vaccination era were independently associated with CAPA development. CAPA remained an independent risk factor associated with mortality risk during the vaccination era., Conclusions: The presence of EORTC/MSGERC host factors for invasive mold disease is associated with increased CAPA incidence and worse outcome parameters, and it is the main driver for the significantly higher incidence of CAPA in the vaccination era. Our findings warrant investigation of antifungal prophylaxis in critically ill patients with COVID-19., Competing Interests: Potential conflicts of interest. S. F. and L. V. report PhD funding from the Research Foundation–Flanders (FWO; grants 11M6922N and 11E9819N). S. F. reports receipt of travel grants from Pfizer and Gilead and speaker fees from Healthbook. K. L. received consultancy fees from MRM Health, Merck Sharp and Dohme (MSD), and Mundipharma, speaker fees and travel support from Pfizer and Gilead, and a service fee from Thermo Fisher Scientific and TECOmedical and participated on an advisory board for MSD. Y. D. received travel grants from Pfizer (travel/congress attendance support) and declares participation on advisory boards for Pfizer and MSD. G. H. and R. V. are senior clinical research fellows of FWO. G. H. received travel fees from Eurosets for the 2023 Extracorporeal Life Support Organization meeting. M. H. received grants from Astellas, Gilead, MSD, Pfizer, Euroimmun, IMMY, Mundipharma, F2G, Pulmocide, and Scynexis and research funding from Gilead Sciences, Astellas, Mundipharma, Euroimmun, MSD, Pulmocide, IMMY, Scynexis, F2G, and Pfizer. J. M. received grants from Bio-Rad, Gilead Sciences, MSD, F2G, Mundipharma, and Pfizer; personal fees and nonfinancial support from Astellas, Basilea, Gilead Sciences, MSD, F2G, Mundipharma, and Pfizer; and personal fees from Bio-Rad. M. P. received travel fees from Pfizer (March 2023; registration for the 2023 International Symposium on Intensive Care & Emergency Medicine (ISICEM) in Brussels, Belgium). I. S. received funding from the Clinical Research Fund, University Hospitals Leuven, investigator-initiated grants from Pfizer, and speaker and travel fees from Pfizer, Gilead, and MSD, and reports participation on an advisory board for Pfizer and Gilead, and receipt of study drugs from MSD. L. V. received support for public doctoral defense from Pfizer and travel fees for conference attendance from Gilead Sciences and Pfizer and reports a PhD fellowship (grant 11E9819N) from FWO. R. V. reports an FWO fellowship and grant (grant G060322N). E. V. W. received travel fees from Gilead (for travel, hotel, and registration). J. W. received investigator-initiated grants from Pfizer, Gilead, and MSD and speaker and travel fees from Pfizer, Gilead, and MSD, and declares participation on advisory boards of Pfizer and Gilead and receipt of study drugs from MSD. J. W. also reports funding from the European Union's Horizon 2020 research and innovation program (grant 847507 HDM-FUN) and FWO project funding (grant G053121N). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant., Methods: This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs)., Results: All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study., Conclusions: Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis., Methods: Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety., Results: Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9--1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups., Conclusions: This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups., Clinical Trials Registration: NCT00413218., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Solid organ transplant (SOT) recipients are at risk of nocardiosis, a rare opportunistic bacterial infection, but prognosis and outcome of these patients are poorly defined. Our objectives were to identify factors associated with 1-year mortality after nocardiosis and describe the outcome of patients receiving short-course antibiotics (≤120 days)., Methods: We analyzed data from a multicenter European case-control study that included 117 SOT recipients with nocardiosis diagnosed between 2000 and 2014. Factors associated with 1-year all-cause mortality were identified using multivariable conditional logistic regression., Results: One-year mortality was 10-fold higher in patients with nocardiosis (16.2%, 19/117) than in control transplant recipients (1.3%, 3/233, P < .001). A history of tumor (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8), invasive fungal infection (OR, 1.3; 95% CI, 1.1-1.5), and donor age (OR, 1.0046; 95% CI, 1.0007-1.0083) were independently associated with 1-year mortality. Acute rejection in the year before nocardiosis was associated with improved survival (OR, 0.85; 95% CI, 0.73-0.98). Seventeen patients received short-course antibiotics (median duration 56 [24-120] days) with a 1-year success rate (cured and surviving) of 88% and a 5.9% risk of relapse (median follow-up 49 [6-136] months)., Conclusions: One-year mortality was 10-fold higher in SOT patients with nocardiosis than in those without. Four factors, largely reflecting general medical condition rather than severity and/or management of nocardiosis, were independently associated with 1-year mortality. Patients who received short-course antibiotic treatment had good outcomes, suggesting that this may be a strategy for further study., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Background: Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients., Methods: We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis., Results: One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2-244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02-1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00-1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms., Conclusions: We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Transplant recipients are at risk for invasive aspergillosis (IA), associated with a significant mortality rate. Renal transplant-specific risk factors have not been established., Methods: Forty-one adult kidney transplant recipients diagnosed with proven or probable IA from 1995 through 2013 were identified by search of the computerized patient files in the University Hospitals Leuven. The control population in this 1:2 case-control study consisted of the 2 patients who received a kidney transplant immediately before and after each identified patient and did not develop IA (n = 82)., Results: Leukopenia after kidney transplant increased the risk of IA among all patients (odds ratio [OR], 2.345 [95% confidence interval {CI}, 1.084-5.071]). For early-onset infection (ie, occurred during the first 3 months after transplant), a longer duration of renal replacement therapy pretransplant and the occurrence of leukopenia were risk factors (OR per year, 1.192 [95% CI, 1.006-1.413] and OR, 3.346 [95% CI, 1.063-10.527], respectively), whereas donor cytomegalovirus seropositivity increased the risk for late-onset IA (ie, occurred >3 months after transplant) (OR, 3.677 [95% CI, 1.388-9.743]). Twelve-week mortality rate was 39%. Disseminated infection, leukopenia, and the height of the serum galactomannan index were associated with an increased risk of death (hazard ratio [HR], 5.080 [95% CI, 1.740-14.830]; HR, 3.198 [95% CI, 1.183-8.649]; and HR, 1.371 [95% CI, 1.123-1.674], respectively)., Conclusions: Prolonged renal replacement therapy before kidney transplant increases the risk of IA early after transplant. The height of the serum galactomannan index predicts mortality., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles., Methods: In this European, multicenter, open-label, 96-week study, antiretroviral-naive adult subjects with human immunodeficiency virus (HIV) infection were randomized to receive either abacavir-lamivudine or tenofovir-emtricitabine with efavirenz. Primary analyses were conducted after 48 weeks of treatment. Bone mineral density (BMD), a powered secondary end point, was assessed by dual energy x-ray absorptiometry. Bone turnover markers (osteocalcin, procollagen 1 N-terminal propeptide, bone specific alkaline phosphatase, and type 1 collagen cross-linked C telopeptide [CTx]) were assessed in an exploratory analysis., Results: A total of 385 subjects were enrolled in the study. BMD loss was observed in both treatment groups, with a significant difference in the change from baseline in both total hip (abacavir-lamivudine group, -1.9%; tenofovir-emtricitabine group, -3.6%; P < .001) and lumbar spine (abacavir-lamivudine group, -1.6%; tenofovir-emtricitabine group, -2.4%; P = .036). BMD loss of >or=6% was more common in the tenofovir-emtricitabine group (13% of the tenofovir-emtricitabine group vs 3% of the abacavir-lamivudine group had a loss of >or=6% in the hip; 15% vs 5% had a loss of >or=6% in the spine). Bone turnover markers increased in both treatment groups over the first 24 weeks, stabilizing or decreasing thereafter. Increases in all markers were significantly greater in the tenofovir-emtricitabine treatment group than in the abacavir-lamivudine group at week 24. All but CTx remained significantly different at week 48 (eg, osteocalcin: abacavir-lamivudine group, +8.07 mg/L; tenofovir-emtricitabine group, +11.92 mg/L; P < .001)., Conclusions: This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine.

Data regarding the incidence of invasive aspergillosis (IA) in the intensive care unit (ICU) are scarce, and the incidence varies. An incidence of 5.8% in a medical ICU has been reported. The majority of patients did not have a hematological malignancy, and conditions such as chronic obstructive pulmonary disease and liver failure became recognized as risk factors. Diagnosis of IA remains difficult. Mechanical ventilation makes it difficult to interpret clinical signs, and radiological diagnoses are clouded by underlying lung pathologies. The significance of a positive respiratory culture result is greatly uncertain, because cultures of respiratory specimens have low sensitivity (50%) and specificity (20%-70%, depending on whether the patient is immunocompromised). The use of serologic markers has never been validated in an ICU population. Limited experience with the detection of galactomannan in bronchoalveolar lavage fluid specimens has yielded promising results. Because of a delay in the diagnosis of IA, the mortality rate exceeds 50%. Recently, our therapeutic armamentarium against IA has improved. Data concerning the safety and efficacy of new antifungal agents in the ICU setting, however, are lacking.

Background: Atazanavir is a once-daily protease inhibitor (PI) for the treatment of human immunodeficiency virus (HIV) infection that has previously been studied in cohorts of treatment-naive and treatment-experienced patients. Limited data are available on the usefulness of switching from a PI-based regimen to a regimen based on a different PI, such as atazanavir, in HIV-infected patients experiencing virologic suppression but seeking regimen simplification., Methods: The Switch to Another Protease Inhibitor (SWAN) study was a 48-week, open-label trial involving HIV-positive patients with virologic suppression who were receiving stable PI-based regimens (with or without ritonavir). Patients were randomized 2 : 1 to switch to atazanavir (400 mg per day)--or, if they were receiving tenofovir, to atazanavir-ritonavir (300/100 mg per day)--or to continue to receive their existing PI. The proportion of patients who experienced virologic rebound (defined as an HIV RNA load >or=50 copies/mL) was compared through study week 48., Results: Patients either received an atazanavir-containing regimen (278 patients) or continued to receive a comparator PI-containing regimen (141 patients). The proportion of patients who experienced virologic rebound was significantly lower among those who switched to an atazanavir-containing regimen (19 [7%] of 278) than it was among those who continued to receive a comparator PI regimen (22 [16%] of 141; P=.004). Patients who switched to atazanavir therapy experienced significantly fewer total cholesterol, fasting triglyceride, and non-high density lipoprotein cholesterol elevations than did patients in the comparator PI group (P<.001); patients receiving atazanavir had comparable rates of adverse event-related discontinuation and serious adverse events., Conclusions: In patients with virologic suppression who were receiving other PIs, switching to a once-per-day regimen containing atazanavir provided better maintenance of virologic suppression (as demonstrated by significantly lower rates of virologic rebound and treatment failure than those observed with continued unmodified therapy), a comparable safety profile, and improved lipid parameters, compared with those for patients who continued their prior PI-based regimen through 48 weeks.

In a large university hospital, the rate of noncompliance with the Infectious Diseases Society of America guidelines for treatment of catheter-related bloodstream infection (CRBSI) was 44% during 52 consecutively observed episodes of CRBSI. To decrease noncompliance, the physicians who provided care to the next 46 patients with CRBSI received standardized treatment advice by electronic mail. This simple and not labor-intensive intervention decreased guideline noncompliance from 44% to 15% (P<.01).

To investigate whether institution of maximal sterile barrier precautions (SBPs) during arterial catheter (AC) insertion prevents catheter colonization, as is the case for central venous catheters (CVCs), a randomized study was conducted. Three hundred seventy-three patients in whom a radial or dorsalis pedis AC was going to be inserted were randomized to an SBP group or a standard-of-care group. These patients, in addition to all patients who were admitted to the unit with an AC already in place or who were not eligible for the randomized study, were observed for AC-related colonization and infection. Data for 272 randomized patients were available for analysis. The colonization incidence was 20.2 cases per 1000 catheter-days in the SBP group and 15.8 cases per 1000 catheter-days in the control group (P>.1). AC-related infection occurred in 3 patients in the SBP group and in 7 patients in the control group (P>.1). Five episodes of AC-related bloodstream infection were diagnosed (1.5 cases per 1000 catheter-days). Use of SBPs did not prevent AC colonization or infection. The incidence of AC-related infectious complications was comparable to the incidence of CVC-related infection reported in the literature.

In clinical trials, the incidence of catheter-tip colonization (CTC) is frequently used as a surrogate end point for the incidence of catheter-related bloodstream infection (BSI). It is not clear whether the correlation between CTC and catheter-related BSI is good. We searched the MEDLINE database and conducted a literature search for the years 1990-2002 and retrieved 29 studies (with a total of 60 study groups) with incidence data on predefined CTC and catheter-related BSI definitions. A good linear correlation between CTC and catheter-related BSI was found (r=0.69; r2=0.48; P<.001). The data from the medical literature about catheter-related infection seem to support the use of CTC as a surrogate end point for catheter-related BSI. In evaluations of clinical interventions or new techniques for the prevention of catheter-related BSI, investigation of the prevention of CTC seems to be a logical first step.