Successful Treatment of Bilateral Renal Mucormycosis With Isavuconazole: A Case Report.

Isolated renal mucormycosis (IRM) is a rare disease with high mortality, more commonly seen in immunocompromised patients. Management has traditionally included antifungal drugs with or without nephrectomy. We present the case of a 34-year-old female with a past medical history of type 1 diabetes mellitus and intravenous heroin use who presented with fever, flank pain, hematuria, and vomiting. She was found to have an oliguric acute kidney injury (AKI) with a serum creatinine (Cr) of 2.5 mg/dL. CT showed bilateral emphysematous pyelonephritis and ureteral cultures grew Rhizopus species. Amphotericin B was started before being switched to isavuconazole due to worsening AKI, and hemodialysis was only required transiently. Rather than the traditional approach to treatment, a conservative approach that preserved kidney function was utilized, and the patient was successfully treated with six months of isavuconazole.

Polymicrobial anaerobic sepsis due to Bacteroides fragilis, Eggerthella lenta, Ruminoccocus gnavus, and Bilophila wadsworthia in a patient with myeloproliferative neoplasm.

We report a rare case of polymicrobial anaerobic bacteremia caused by four different gut anaerobes: Bacteroides fragilis, Eggerthella lenta, Bilophila wadsworthia, and Ruminococcus gnavus. Early initiation of appropriate therapy and species identification with matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) resulted in full recovery from the infection. Our case highlights the clinical significance of polymicrobial cultures and the importance of performing anaerobic cultures for blood specimens to ensure proper identification and treatment.

Rapid and Quantitative Detection of Human Antibodies against the 2019 Novel Coronavirus SARS CoV2 and Its Variants as a Result of Vaccination and Infection.

Measuring the antibody response to 2019 SARS CoV2 is critical for diagnostic purposes, for monitoring the prevalence of infection, and for gauging the efficacy of the worldwide vaccination effort for COVID-19. In this study, a microchip-based grating-coupled fluorescent plasmonic (GC-FP) assay was used to measure antibody levels that resulted from COVID-19 infection and vaccination. In addition, we measured the relative antibody binding toward antigens from the CoV2 virus variants strains B.1.1.7 (Alpha) and B.1.351 (Beta). Antibody levels against multiple antigens within the SARS CoV2 spike protein were significantly elevated for both vaccinated and infected individuals, while those against the nucleocapsid (N) protein were only elevated for infected individuals. GC-FP was effective for monitoring the IgG-based serological response to vaccination throughout the vaccination sequence and also resolved acute (within hours) increases in antibody levels. A significant decrease in antibody binding to antigens from the B.1.351 variant, but not B.1.1.7, was observed for all vaccinated subjects when measured by GC-FP compared to the 2019 SARS CoV2 antigens. These results were corroborated by competitive enzyme-linked immunosorbent assay (ELISA). Collectively, the findings suggest that GC-FP is a viable, rapid, and accurate method for measuring both overall antibody levels to SARS CoV2 and relative antibody binding to viral variants during infection or vaccination. IMPORTANCE In this work, a novel biosensor technology was used to measure antibody levels that resulted from vaccination against COVID-19 and/or from infection with the virus. Importantly, this approach enables quantification of antibody levels, which can provide information about the timing and level of immune response. Due the multiplexed nature of this approach, antibody binding to both the original 2019 SARS CoV-2 strain and variant strains can be performed simultaneously and in a short (30-min) time frame.

Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity.

Coronavirus disease 2019 (COVID-19) is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, including virus-neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveals that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individuals that experience severe disease. The severity-associated increase in SARS-CoV-2-specific antibody is dominated by immunoglobulin G (IgG), with an IgG subclass ratio skewed toward elevated receptor binding domain (RBD)- and S1-specific IgG3. In addition, individuals that experience severe disease show elevated SARS-CoV-2-specific antibody binding to the inflammatory receptor FcÉ£RIIIa. Based on these correlational studies, we propose that spike-specific IgG subclass utilization may contribute to COVID-19 disease severity through potent Fc-mediated effector functions. These results may have significant implications for SARS-CoV-2 vaccine design and convalescent plasma therapy.

Hemorrhagic Cystitis Secondary to Adenovirus and BK Virus Infection in a Diffuse Large B-Cell Lymphoma Patient with Recent CAR T-Cell Therapy.

Patients who undergo chimeric antigen receptor T-cell therapy (CAR T-cell therapy) are immunosuppressed due to multiple factors. While adenovirus and BK virus are well-known pathogens in the context of hematopoietic stem cell transplant, there are no detailed reports of these infections in the setting of CAR T-cell therapy. We describe a 70-year-old male who recently underwent CAR T-cell therapy for diffuse large B-cell lymphoma. He presented with intractable gross hematuria and dysuria. Workup revealed adenovirus viremia and viruria and BK virus viruria. He was treated for adenovirus hemorrhagic cystitis with intravenous cidofovir 1 mg/kg/day, every three days for three weeks, with good clinical response. We also discuss the mechanisms of immunosuppression in CAR T-cell therapy as well as the principles of treatment of adenovirus and BK virus infections in the immunosuppressed patient.

Use of Ceftaroline Fosamil in Osteomyelitis: CAPTURE Study Experience.

BACKGROUND: Osteomyelitis is often challenging to treat. This analysis examined the clinical experience of patients with gram-positive osteomyelitis treated with ceftaroline fosamil in the phase 4 Clinical Assessment Program and Teflaro® Utilization Registry (CAPTURE) study. METHODS: Data including patient demographics, past illnesses, risk factors, disease characteristics, antibiotic use, pathogens isolated, and clinical outcome were collected between September 2013 and February 2015 by review of randomly ordered patient charts from participating sites in the United States. Clinical success was defined as discontinuation of ceftaroline fosamil following clinical cure with no further need for antibiotics or clinical improvement with switch to another antibiotic treatment. RESULTS: A total of 150 patients with gram-positive osteomyelitis were treated with ceftaroline fosamil. Most patients (117/150; 78.0%) were treated with 600 mg ceftaroline fosamil per dose; 143/150 patients (95.3%) received a dose every 12 h. The majority (89/150 patients; 59.3%) had been previously diagnosed with diabetes mellitus or peripheral arterial disease. Osteomyelitis was associated with hardware in 32/150 patients (21.3%). Methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA; MSSA) were the most commonly isolated pathogens, observed in 93/150 (62.0%) and 21/150 (14.0%) patients, respectively. Clinical success with ceftaroline fosamil therapy was observed in 139/150 (92.7%) patients overall, 81/89 (91.0%) patients with diabetes or peripheral arterial disease, and 18/20 (90.0%) patients who had hardware implanted before ceftaroline fosamil therapy (none had hardware removed during therapy). Patients who received prior antibiotic therapy or ceftaroline fosamil as monotherapy experienced clinical success rates of 93.9% (107/114) and 91% (91/100), respectively. Among patients who received concurrent antibiotic therapy, the clinical success rate was 96.0% (48/50). Patients who were infected with MRSA or MSSA had clinical success rates of 92.5% (86/93) and 100% (21/21), respectively. A total of 2/150 (1.3%) patients discontinued ceftaroline fosamil therapy because of adverse events. CONCLUSIONS: Clinical success rates with ceftaroline fosamil were high in patients with gram-positive osteomyelitis, including those with diabetes or peripheral arterial disease and those with MRSA or MSSA.

Prevalence and impact of baseline resistance-associated substitutions on the efficacy of ledipasvir/sofosbuvir or simeprevir/sofosbuvir against GT1 HCV infection.

Baseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or more drug classes. Baseline LDV RASs in GT1a, TE, and cirrhosis LDV/SOF subgroup was associated with 2-4% lower SVR12 rates. SMV RASs was associated with lower SVR12 rates in GT1a, treatment-experienced, cirrhotics SMV/SOF subgroup. Pooled analysis of all patients with baseline RASs revealed that SVR12 was 100% (19/19) in patients treated for longer than 98 days but was 87% (81/93) in patients treated for shorter than 98 days. These results demonstrate that RASs prevalence and their impact in real world practice are in general agreement with registration trials, and suggest that longer treatment duration may overcome the negative impact of baseline RASs on SVR12 rates in clinical practice.

Ceftaroline fosamil for the treatment of community-acquired bacterial pneumonia in the intensive care unit.

The Clinical Assessment Program and Teflaro(®) Utilization Registry (CAPTURE) is a multicenter study evaluating the clinical use of ceftaroline fosamil in patients with community-acquired bacterial pneumonia (CABP) or acute bacterial skin and skin structure infection. Data were collected between August 2011 and February 2013, from 398 evaluable patients receiving treatment at 33 sites in the USA. This manuscript presents data collected from patients with CABP who received care in an intensive care unit (ICU) or in general medical wards (35% and 64% of evaluable patients, respectively). The majority of ICU and general medical ward patients had underlying comorbidities (78% and 74%, respectively), with structural lung disease being the most common (42% in the ICU and 40% in general medical wards). Patients admitted to the ICU had a longer duration of stay, a longer duration of symptoms before treatment, and a longer duration of ceftaroline fosamil therapy than did general medical ward patients. Most patients treated in the ICU and in general medical wards were given ceftaroline fosamil as second-line therapy (87% and 80%, respectively). The overall rate of clinical success for patients treated with ceftaroline fosamil was 68% in the ICU and 85% in the general medical wards. Clinical success for patients receiving ceftaroline fosamil as a second-line agent was 84% in the ICU and 86% in general medical wards. These findings indicate that ceftaroline fosamil is a viable treatment option for CABP, both in the ICU and in general medical wards.

Safety profile of boceprevir and telaprevir in chronic hepatitis C: real world experience from HCV-TARGET.

BACKGROUND & AIMS: The safety profiles of boceprevir and telaprevir in the treatment of chronic hepatitis C, administered in academic and community centres across the United States, were evaluated. METHODS: In 90 medical centres, patients with chronic HCV received pegylated interferon, ribavirin, and either telaprevir or boceprevir per local standard of care. Demographic, adverse event, clinical, and virological data were collected during treatment and follow-up. RESULTS: A total of 2084 patients (97% HCV genotype 1) received at least one dose of a protease inhibitor. At baseline, 38% of patients had cirrhosis, and 57% had received at least one prior treatment for hepatitis C. Serious adverse events occurred in 12% of patients receiving protease inhibitor therapy. Overall, 66% of patients experienced anaemia, leading to frequent ribavirin dose reductions (42%) and erythropoietin use (37%); 11% received blood transfusion. More than 90% of patients had adverse events that led to a prescription, treatment, or dosage change, and 39% of patients discontinued treatment early, most commonly because of adverse events (18%) or lack of efficacy (16%). Hepatic decompensation events occurred in 3% of all patients. Age, female gender, cirrhosis, HCV genotype 1 subtype, creatinine clearance, platelet levels, albumin levels and haemoglobin levels were independent predictors of anaemia. Five deaths occurred. Overall, 52% of all patients achieved a sustained virologic response. CONCLUSIONS: In academic and community centres, where chronic hepatitis C patients commonly have advanced liver disease, triple therapy was associated with a high rate of adverse events and involved frequent treatment modifications and adverse event management.

Ceftaroline fosamil for treatment of diabetic foot infections: the CAPTURE study experience.

BACKGROUND: To ascertain which demographic, clinical, and microbiological factors might affect clinical outcomes of patients with diabetic foot infections, excluding known osteomyelitis, by analysing Clinical Assessment Program and Teflaro® Utilization Registry study data of patients treated with ceftaroline fosamil. METHODS: At participating study centres, we collected data by randomized selection and chart review, including patient demographics, co-morbidities, infecting pathogens, antibiotic use, surgical interventions, and clinical response. Evaluable patients were those with data sufficient to determine clinical outcome. Clinical success was defined as clinical cure with no use of other antibiotics or clinical improvement with a switch to oral antibiotic therapy at the end of intravenous ceftaroline fosamil treatment. RESULTS: Among 201 patients (mean age 61.7 years, mean body mass index 33.2 and 57% male patients), 40% had peripheral vascular disease. Prior antibiotic therapy had been given to 161 (80%) of the patients, most commonly with vancomycin and/or piperacillin-tazobactam. Patients received ceftaroline fosamil for mean duration of 6.1 days (range 1-30), as monotherapy in 130 (65%) patients and concurrently with other antibiotics in 71 (35%). Bacterial pathogens were identified in 114 (57%) of the patients; methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus were isolated from 56 (49%) and 28 (25%) of culture-positive patients respectively. Clinical success was noted in 81% of patients and was not significantly associated with co-morbidities, pathogen type, or need for surgical intervention. CONCLUSIONS: Ceftaroline fosamil treatment of diabetic foot infections was associated with high clinical success, including inpatients with obesity, co-morbidities, or methicillin-resistant Staphylococcus aureus or mixed infections or requiring surgical intervention.

Contemporary use of ceftaroline fosamil for the treatment of community-acquired bacterial pneumonia: CAPTURE study experience.

The Clinical Assessment Program and Teflaro(®) Utilization Registry (CAPTURE) is a multicenter cohort study designed to collect information on the contemporary use of ceftaroline fosamil in the US. Data collected from 398 evaluable patients with community-acquired bacterial pneumonia (CABP) (mean age 64 years) during the first 18 months of the study are presented. Most patients had co-morbidities (76%; primarily structural lung disease), and ≧2 signs and symptoms of CABP (76%). Overall clinical success was 79% which varied little with ceftaroline fosamil usage (monotherapy vs concurrent therapy; first-line vs second-line therapy). Most patients were discharged home (60%) or to another healthcare facility (35%). These data suggest that ceftaroline, in contemporary clinical use, is an effective antibiotic for the treatment of patients with CABP, including those with significant co-morbidities or who required a change of their prior antibiotic therapy.