Oritavancin Versus Daptomycin for Osteomyelitis Treatment After Surgical Debridement.

INTRODUCTION: Weekly intravenous (IV) oritavancin and daily daptomycin were compared in an outpatient setting following extensive surgical debridement for treating patients with osteomyelitis. METHODS: This was a retrospective, observational study of patients diagnosed with acute osteomyelitis. Exclusion criteria were the use of Gram-negative antibiotic therapy, use of antibiotics for more than 48 h prior to oritavancin or daptomycin or prior use of > 2 doses of oritavancin or more than 4 weeks of daptomycin. Clinical success was resolution or improvement of symptoms and no further treatment. Data were analyzed with Chi-square test or Fisher's exact test. RESULTS: Consecutive outpatients (n = 150) with acute osteomyelitis who were treated with oritavancin or daptomycin (1:1) following extensive surgical debridement were identified. Staphylococcus aureus was the most common pathogen (n = 117). No patient in either group received prior antibiotic therapy (previous 30 days) or was hospitalized within 90 days prior to surgical debridement. Twenty-one (28%) patients prescribed oritavancin had chronic kidney disease, seven of whom were receiving hemodialysis or peritoneal dialysis. Compared to oritavancin, patients prescribed daptomycin had higher rates of all-cause readmission [odds ratio (OR) 2.89; p < 0.001], more infection-related readmission (OR 3.19; p < 0.001), and greater likelihood of receiving antibiotics post-discontinuation of initial therapy (OR 2.13; p < 0.001). Repeat surgical debridement was required for 68.0% with daptomycin vs. 23.1% with oritavancin (p < 0.001). CONCLUSIONS: Oritavancin demonstrated a significantly higher rate of clinical success compared to daptomycin, with lower all-cause and infection-related readmissions, reduced need for repeat surgical debridement, and fewer additional antibiotic requirements.

Persistent SARS-CoV-2 infectivity greater than 50 days in a case series of allogeneic peripheral blood stem cell transplant recipients.

The coronavirus disease 19 (COVID-19) pandemic has infected tens of millions across the world, but there is a significant gap in our understanding about COVID-19 in the hematopoietic stem transplant (HSCT) recipient population. Prolonged viral shedding is frequently observed with severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), but studies suggest viral loads decline 10 days after symptom onset. Current CDC guidance suggests that severely ill and immunocompromised hosts are no longer infectious after 20 days from symptom onset. Cycle threshold (Ct) values are inversely proportional to the viral load and are used to detect SARS-CoV-2 RNA concentration. Specimens with reverse transcriptase PCR (RT-PCR) Ct values > 33-34 have been associated with inability to culture virus, and have been used as a surrogate for diminished infectivity. We report two cases of  allogeneic peripheral blood stem cell transplant (PBSCT) recipients who had prolonged durations of infectivity with SARSCov-2, based on culture positivity and persistently low Ct values for greater than 50 days.

Early Tocilizumab Dosing Is Associated With Improved Survival in Critically Ill Patients Infected With Severe Acute Respiratory Syndrome Coronavirus-2.

To identify the most efficacious timing for tocilizumab administration in critically ill patients infected with severe acute respiratory syndrome coronavirus-2. DESIGN: Observational multicenter cohort study. SETTING: A total of 23 acute care hospitals in four states. PATIENTS: One-hundred eighteen patients admitted between March 13, 2020, and April 16, 2020. Eighty-one patients received tocilizumab, and 37 were untreated and served as a control group. MEASUREMENTS AND MAIN RESULTS: The main outcome was mortality and was analyzed by timing of tocilizumab dosing. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered greater than 1 day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was used for comparison. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated (p = 0.003). Dosing tocilizumab late was associated with an increased mortality compared with the untreated group (p = 0.006). CONCLUSIONS: Early tocilizumab administration was associated with decreased mortality in critically ill severe acute respiratory syndrome coronavirus-2 patients, but a potential detriment was suggested by dosing later in a patient's course.

Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2.

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).

SARS-CoV2 and Co-Infections: A Review of Two Cases.

COVID-19 infection caused by SARS-CoV2 virus is an acute respiratory illness which was declared as a pandemic by the World Health Organization. Usually, SARS-CoV2 infects independently and can cause spectrum of disease ranging from mild illness to severe progressive pneumonia, multiorgan dysfunction, and death; however, co-infections with other respiratory pathogens have been noted. Here, we present 2 fatal cases with co-infection, one with parainfluenza-4 virus and other co-infection/secondary infection with Streptococcus pneumoniae bacteria. Further studies are needed to study the effect of co-infections on morbidity and mortality of patients and establish the outcome of such infections.

A Real-World Assessment of Clinical Outcomes and Safety of Eravacycline: A Novel Fluorocycline.

BACKGROUND: Eravacycline is a novel fluorocycline approved for treatment of intraabdominal infections, with a broad spectrum of activity against a range of pathogens including multidrug-resistant species, including ESBL- or KPC-producing isolates. It is approved for twice-daily dosing with no need for adjustment in renal dysfunction. In the concomitant administration with CYP 3A4-inducing drugs, eravacycline dosing should be modified. OBJECTIVE: To evaluate the efficacy and safety of eravacycline in a range of infections such as intraabdominal infections, pneumonia and diabetic foot infections in seriously ill patients. METHODS: A retrospective observational cohort study using electronic patient records of 50 consecutive patients administered eravacycline during inpatient acute care admission or as part of outpatient antibiotic therapy (OPAT). RESULTS: Therapy of 1.5 mg/kg q24h was initiated in the hospital in most patients, although some of the less sick were managed in the office or OPAT setting. All patients concluded their management outside of the hospital. Of the 50 patients, 47 (94%) achieved clinical resolution of their infection and 3 (6%) clinical failures occurred. Only three (6%) patients did not have comorbidities, three had a single comorbidity (6%), and the majority (88%) of patients had two or more comorbidities. Most common infections were intraabdominal (36%), pneumonia (18%), diabetic foot (12%), spontaneous bacterial peritonitis (8%) and empyema (8%). Almost half of infections had more than one pathogen isolated, and resistant isolates were frequent. The drug was well tolerated with only two reports of nausea, which did not result in treatment discontinuation, and in 30 days of post-eravacycline therapy only one case of Clostridiodes difficile. CONCLUSIONS: In this real-world setting, eravacycline demonstrated a similar high level of clinical efficacy as seen in clinical trials, 94%, in a variety of infections, including against multidrug-resistant bacteria, and was well tolerated.

Treatment of Acute Osteomyelitis with Once-Weekly Oritavancin: A Two-Year, Multicenter, Retrospective Study.

BACKGROUND: Acute osteomyelitis is typically caused by Gram-positive pathogens, commonly antibiotic-resistant Staphylococcus species. Standard antibiotic treatment is challenging due to required multiple daily doses, therapeutic drug monitoring, and parenteral administration for at least 4 weeks. Oritavancin is a long-acting lipoglycopeptide antibiotic approved as a single 1200 mg dose for the treatment of adult patients with acute bacterial skin and skin structure infections. OBJECTIVE: To characterize the real-world use, efficacy, and safety of oritavancin in adult patients with acute osteomyelitis. METHODS: This was a 2-year, multicenter, retrospective, descriptive study of patients treated for acute osteomyelitis with weekly doses of oritavancin. End of therapy evaluation (ETE) was defined as evaluation at 7-10 days after the last dose of oritavancin, and post-therapy assessment (PTE) was at 3 months and 6 months. At ETE and PTE, patients were interviewed via telephone for clinical outcomes, using a standard questionnaire. Electronic medical record review was also conducted. RESULTS: 134 patients were treated with oritavancin for acute osteomyelitis across 20 different Metro Infectious Disease Consultants infusion centers in six states. Of total positive cultures, 71.9% (92/128) were methicillin-resistant Staphylococcus aureus (MRSA) from deep wounds, bone, or joint culture; an additional nine (6.7%) of 134 patients presented with concomitant MRSA bacteremia. Oritavancin was administered via intravenous catheter; patients received an initial treatment of 1200 mg and then 800 mg weekly thereafter for a total number of doses of four (n = 118) or five (n = 16). 118 patients (88.1%) of the baseline 134 patients achieved clinical success at the ETE timepoint. 130 patients were available for PTE at 3 months and 6 months. Overall, relapse or persistent infection was diagnosed in 13/134 (9.7%) patients. Nine (6.7%) of 134 patients were admitted to the hospital during the follow-up period but none for osteomyelitis. Adverse events were reported in five (3.7%) patients including hypoglycemia-related symptoms (three patients), tachycardia (one patient), and tachycardia with chest pain (one patient). None of these patients were hospitalized due to adverse events, and all patients eventually finished their treatment regimens. CONCLUSION: This is the largest real-world clinical study of adult patients treated with oritavancin for acute osteomyelitis. Use of oritavancin for acute osteomyelitis infection resulted in a high rate of positive clinical outcomes and a low incidence of adverse events, thereby providing potential for a convenient, effective, and safe therapeutic option. Future prospective and comparative studies are needed to validate these findings.

Contralateral compartment syndrome inoculated by invasive group A streptococcus.

Compartment syndrome is a rare but a well-documented complication in patients with trauma-induced group A streptococcus infection. Here, we present a case of a male who developed compartment syndrome on the left lower extremity after an injury inoculated by group A streptococcus on the right lower extremity. The patient was resuscitated with antibiotics, urgent fasciotomy, and immunoglobulin. The patient was eventually transferred to a burn center for further care.

Value and Clinical Impact of an Infectious Disease-Supervised Outpatient Parenteral Antibiotic Therapy Program.

Background. Outpatient parenteral antibiotic therapy (OPAT) is a safe and effective modality for treating serious infections. This study was undertaken to define the value of OPAT in a multicentered infectious disease (ID) private practice setting. Methods. Over a period of 32 months, 6120 patients were treated using 19 outpatient ID offices in 6 states. Analysis included patient demographics, indications of OPAT, diagnoses, therapeutic agent, duration of therapy, and site of therapy initiation. Outcomes were stratified by therapeutic success, clinical relapse, therapeutic complications, and hospitalizations after initiating therapy. Statistical analysis included an ordinal logistic regression analysis. Results. Forty-three percent of patients initiated therapy in an outpatient office, and 57% began therapy in a hospital. Most common diagnoses treated were bone and joint (32.2%), abscesses (18.8%), cellulitis (18.5%), and urinary tract infection (10.8%). Ninety-four percent of patients were successfully treated, and only 3% were hospitalized after beginning therapy. Most common cause of treatment failure was a relapse of primary infection (60%), progression of primary infection (21%), and therapeutic complication (19%). Conclusions. An ID-supervised OPAT program is safe, efficient, and clinically effective. By maximizing the delivery of outpatient care, OPAT provides a tangible value to hospitals, payers, and patients. This program is a distinctive competency available to ID physicians who offer this service to patients.

Transfer from high-acuity long-term care facilities is associated with carriage of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae: a multihospital study.

OBJECTIVE: To determine whether transfer from a long-term care facility (LTCF) is a risk factor for colonization with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae upon acute care hospital admission. DESIGN: Microbiologic survey and nested case-control study. SETTING: Four hospitals in a metropolitan area (Chicago) with an early KPC epidemic. PATIENTS: Hospitalized adults. METHODS: Patients transferred from LTCFs were matched 1∶1 to patients admitted from the community by age (± 10 years), admitting clinical service, and admission date (± 2 weeks). Rectal swab specimens were collected within 3 days after admission and tested for KPC-producing Enterobacteriaceae. Demographic and clinical information was extracted from medical records. RESULTS: One hundred eighty patients from LTCFs were matched to 180 community patients. KPC-producing Enterobacteriaceae colonization was detected in 15 (8.3%) of the LTCF patients and 0 (0%) of the community patients ([Formula: see text]). Prevalence of carriage differed by LTCF subtype: 2 of 135 (1.5%) patients from skilled nursing facilities without ventilator care (SNFs) were colonized upon admission, compared to 9 of 33 (27.3%) patients from skilled nursing facilities with ventilator care (VSNFs) and 4 of 12 (33.3%) patients from long-term acute care hospitals (LTACHs; [Formula: see text]). In a multivariable logistic regression model adjusted for a propensity score that predicted LTCF subtype, patients admitted from VSNFs or LTACHs had 7.0-fold greater odds of colonization (ie, odds ratio; 95% confidence interval, 1.3-42; [Formula: see text]) with KPC-producing Enterobacteriaceae than patients from an SNF. CONCLUSIONS: Patients admitted to acute care hospitals from high-acuity LTCFs (ie, VSNFs and LTACHs) were more likely to be colonized with KPC-producing Enterobacteriaceae than were patients admitted from the community. Identification of healthcare facilities with a high prevalence of colonized patients presents an opportunity for focused interventions that may aid regional control efforts.

Rectal screening for Klebsiella pneumoniae carbapenemases: comparison of real-time PCR and culture using two selective screening agar plates.

Klebsiella pneumoniae carbapenemases (KPCs) have recently been described in Chicago, IL, especially among residents of long-term acute care hospitals (LTACHs). These patients are frequently transferred to local Chicago hospitals for higher acuity of medical care, and rapid detection and isolation of KPC-colonized LTACH residents may interrupt the introduction of KPCs into acute care hospitals. We evaluated the performance of a real-time PCR for bla(KPC) from enrichment broth versus direct plating of rectal surveillance swabs on two selective culture media, CHROMagar extended-spectrum-ß-lactamase (ESBL) and vancomycin, amphotericin B, ceftazidime, and clindamycin (VACC) plates. Rectal surveillance swabs were collected as part of a point prevalence study of KPC carriage rates among 95 residents of two Chicago area LTACHs. Discrepant results between PCR and culture were resolved by subculturing the enrichment broth. Overall, 66 of 95 patients (69.5%) were colonized with KPCs, using the cumulative results of culture as a reference standard. Real-time PCR from enrichment broth was positive in 64 of 66 (97%) colonized patients, including nine surveillance swabs that were missed by both selective culture media. PCR demonstrated higher sensitivity, 97.0%, than culture using either CHROMagar or VACC plates (both with sensitivity of 77.3%). In addition, turnaround time was significantly shorter for the PCR-based method than for culture, with a mean of 24 h versus 64 to 72 h for CHROMagar and VACC plates (P < 0.0001). Overall, PCR for bla(KPC) represents the best screening test for KPCs with significantly higher sensitivity and with less hands-on time, resulting in a shorter time to results.

Graphene from electrochemical exfoliation and its direct applications in enhanced energy storage devices.

Graphite was electrochemically exfoliated in mixtures of room temperature ionic liquids and deionized water containing lithium salts to produce functionalized graphenes and such an electrochemical exfoliation technique can be directly used in making primary battery electrodes with significantly enhanced specific energy capacity.

Kikuchi-Fujimoto disease: hydroxychloroquine as a treatment.

We describe a case of recurrent Kikuchi's disease in a South Asian-American man that was treated successfully with chloroquine and on recurrence with hydroxychloroquine. Each treatment led to a very prompt response.