Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 µg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (r = 0.37, P < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC50) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.

Incidence and outcome of invasive fungal diseases after allogeneic hematopoietic stem cell transplantation: A Swiss transplant cohort study.

Contemporary, comprehensive data on epidemiology and outcomes of invasive fungal disease (IFD) including breakthrough IFD among allogeneic hematopoietic stem cell transplantation (HSCT) recipients are scarce. We included 479 allogeneic HSCT recipients with 10 invasive candidiasis (IC) and 31 probable/proven invasive mold disease (IMD) from the Swiss Transplant Cohort Study from 01.2009 to 08.2013. Overall cumulative incidence was 2.3% for IC and 8.5% for probable/proven IMI: 6% for invasive aspergillosis (IA) and 2.5% for non-AspergillusIMI. Among 41 IFD, 46% IFD were breakthrough, with an overall incidence of 4.6%, more frequently caused by other-than-Aspergillus fumigatus molds than primary IFD (47.6% (10/21) vs 13% (3/23), P = 0.04). Twelve-week mortality among patients with IC was 20% and 58.6% for probable/proven IMD (60% IA and 54.6% non-Aspergillus). Our results reveal that breakthrough IFD represent a marked burden of probable/proven IFD postallogeneic HSCT and mortality remains above 50% in patients with probable/proven IMD, underscoring the ongoing challenges to prevent and treat IFD in these patients.

Case report: when two and ½ men go camping .

BACKGROUND: In patients, rapid identification of bacterial species may help to guide treatment at early stages. New protocols for the identification directly from positive blood culture flasks significantly helped in the presented case report. CASE PRESENTATION: Two patients (a father and son) presented with diarrhea, malaise, and fever of 3 to 4 days duration. Blood cultures from both patients cultured short Gram-positive rods. MALDI-TOF based rapid identification protocol direct from positive blood culture identified Listeria monocytogenes as the cause of sepsis and could be confirmed with conventional methods. Listeria monocytogenes was identified 24 h later by conventional biochemical identification methods (VITEK 2). Antibiotic treatment was adjusted early in response to the MALDI-TOF based identification of bacteremia. Pulsed field gel electrophoresis confirmed the suspected relatedness of the father's and son's isolates. CONCLUSIONS: MALDI-TOF based may provide a rapid identification of bacterial species directly from positive blood culture.

Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation and Association With Occurrence and Outcome of Invasive Aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) remains a leading cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To date, no reliable immunological biomarkers for management and outcome of IA exist. Here, we investigated reconstitution of antifungal immunity in patients during the first 12 months after HSCT and correlated it with IA. METHODS: Fifty-one patients were included, 9 with probable/proven IA. We determined quantitative and qualitative reconstitution of polymorphonuclear (PMN), CD4, CD8, and natural killer (NK) cells against Aspergillus fumigatus over 5 time points and compared the values to healthy donors. RESULTS: Absolute CD4 and CD8 cell counts, antigen-specific T-cell responses, and killing capacity of PMN against A. fumigatus were significantly decreased in all patients over 12 months. In patients with probable/proven IA, reactive oxygen species (ROS) production tended to be lower compared to patients without IA, and absolute NK-cell counts remained below 200 cells/µL. Patients with well-controlled IA showed significantly higher ROS production and NK-cell counts compared to patients with poor outcome. CONCLUSIONS: This study highlights the importance of functional PMN, T-cell, and NK-cell immunity for the outcome of IA. Larger multicenter studies should address the potential use of NK-cell counts for the management of antifungal therapy.

Community-acquired and hospital-acquired respiratory tract infection and bloodstream infection in patients hospitalized with COVID-19 pneumonia.

OBJECTIVES: SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. METHODS: We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections. RESULTS: In the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4-74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8-18) and time to bloodstream infection 14 days (IQR, 6-30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients. CONCLUSIONS: Community-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

[A Holiday Souvenir with Consequences - an Interdisciplinary Challenge]. / Folgenreiches Feriensouvenir ­ eine interdisziplinäre Herausforderung.

A Holiday Souvenir with Consequences - an Interdisciplinary Challenge Abstract. We describe a patient with a diabetic foot and challenging infectious complications. After a hospital stay in Sri Lanka due to a soft tissue infection of the foot he was relocated to Switzerland. After proof of multiple resistant bacteria, an amputation of the forefoot with a split skin cover was performed, followed by a short resistance-adapted antibiotic treatment, with good clinical results. This case illustrates the increase of multidrug-resistant bacteria, even in Switzerland. It emphasizes the importance of infection control measures in travellers returning from countries with high prevalence of multidrug-resistant bacteria (especially after a hospitalisation), and the need of a close interdisciplinary collaboration in these cases to guarantee the best treatment and to limit the spreading of multidrug-resistant bacteria.

Community-Acquired Respiratory Paramyxovirus Infection After Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience.

BACKGROUND: Paramyxoviruses include respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (MPV), which may cause significant respiratory tract infectious disease (RTID) and mortality after allogeneic hematopoietic cell transplantation (HCT). However, clinical data regarding frequency and outcome are scarce. METHODS: We identified all paramyxovirus RTIDs in allogeneic HCT recipients diagnosed by multiplex polymerase chain reaction between 2010 and 2014. Baseline characteristics of patients, treatment, and outcome of each episode were analyzed; ie, moderate, severe, and very severe immunodeficiency (verySID) according to HCT ≤6 months, T- or B-cell depletion ≤3 months, graft-versus-host disease, neutropenia, lymphopenia, or hypo-gammaglobulinemia. RESULTS: One hundred three RTID episodes in 66 patients were identified (PIV 47% [48 of 103], RSV 32% [33 of 103], MPV 21% [22 of 103]). Episodes occurred in 85% (87 of 103) at >100 days post-HCT. Lower RTID accounted for 36% (37 of 103). Thirty-nine percent (40 of 103) of RTID episodes required hospitalization and more frequently affected patients with lower RTID. Six percent progressed from upper to lower RTID. Overall mortality was 6% and did not differ between paramyxoviruses. Sixty-one percent (63 of 103) of episodes occurred in patients with SID, and 20.2% (19 of 63) of episodes occurred in patients with verySID. Oral ribavirin plus intravenous immunoglobulin was administered in 38% (39 of 103) of RTIDs, preferably for RSV or MPV (P ≤ .001) and for SID patients (P = .001). Patients with verySID frequently progressed to lower RTID (P = .075), required intensive care unit transfer, and showed higher mortality. CONCLUSION: Paramyxovirus RTID remains a major concern in allogeneic HCT patients fulfilling SID and verySID, emphasizing that efficacious and safe antiviral treatments are urgently needed.