Compassionate Use of Remdesivir for Patients with Severe Covid-19.

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Epidemiology, Resistance Profiles, and Outcomes of Bloodstream Infections in Community-Onset Sepsis in the United States.

OBJECTIVES: To describe frequency of positive blood cultures, patterns of pathogens' characteristics and their resistance profile in patients with blood cultures drawn due to a presumed diagnosis of community-onset sepsis, and to examine the association between blood culture-positive pathogens and hospital mortality. DESIGN: Retrospective cohort study. SETTING: Two hundred one U.S. hospitals from 2016 to 2020 using the Premier Healthcare Database. SUBJECTS: Adult patients presenting with community-onset sepsis who had blood cultures collected within 2 days of hospital admission. We defined sepsis using the U.S. Centers for Disease Control Adult Sepsis Event Surveillance criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 147,061 patients with community-onset sepsis. The number of blood culture-positive sepsis episodes was 21,167 (14%) and the number of nonblood culture-positive sepsis episodes was 20,326 (14%). Among patients with blood culture-positive sepsis, Gram-negative rods were isolated in 55% of patients, Gram-positive cocci were isolated in 47%. Of those, methicillin-resistant Staphylococcus aureus (MRSA) was 11%, ceftriaxone-resistant Enterobacterales /extended-spectrum ß-lactamase was 7%, and carbapenem-resistant Enterobacterales was 1.3%. The crude in-hospital mortality was 17% for culture-negative sepsis, 13% for nonblood culture-positive sepsis, and 17% for blood culture-positive sepsis. In multilevel logistic regression models, compared with culture-negative sepsis, blood culture-positive sepsis (adjusted odds ratio [aOR], 0.89; 95% CI, 0.85-0.94) and nonblood culture-positive sepsis (aOR, 0.82; 95% CI, 0.78-0.87) were associated with lower odds of in-hospital mortality. Acinetobacter species, Pseudomonas aeruginosa , methicillin-sensitive Staphylococcus aureus , and MRSA were associated with higher in-hospital mortality, whereas Escherichia coli , Klebsiella species, Proteus species, and Streptococcus species were associated with lower in-hospital mortality. CONCLUSIONS: In patients hospitalized with community-onset sepsis, the prevalence of blood culture-positive sepsis was 14%. Among positive blood culture sepsis resistant organisms were infrequent. Compared with culture-negative sepsis, blood culture-positive sepsis and nonblood culture-positive sepsis were associated with lower in-hospital mortality.

The microbiology of infected pancreatic necrosis in the era of minimally invasive therapy.

We aimed to determine the microbiology of infected walled-off pancreatic necrosis (WON) in an era of minimally invasive treatment, since current knowledge is based on surgical specimens performed over two decades ago. We retrospectively analyzed a prospectively maintained database of patients who were treated for symptomatic WON using combined endoscopic and percutaneous drainage between 2008 and 2017. Aspirates from WON at initial treatment were evaluated. One hundred eighty-two patients were included with a mean age of 56 of whom 67% were male. Culture results were obtained at a median of 45 days from onset of acute pancreatitis of which 41% were infected. Candida spp. accounted for 27%; yet, multidrug-resistant organisms were found in only five patients. Approximately 64% were transferred to our institution for continuation of care. Of those, 55% were infected, most frequently with Candida spp., Enterococcus spp., and coagulase-negative Staphylococcus. Patients seen and admitted initially at our institution had milder forms of pancreatitis, fewer comorbidities, and 85% had symptomatic sterile WON. Empiric antibiotic use successfully predicted infection 70% of the time. Multivariate analysis demonstrated that elderly age, severity of pancreatitis, and prior use of antibiotics were indicators of infection. Necrotic pancreatic tissue remains sterile in the majority of cases treated with minimally invasive therapy, enabling judicious selection of antibiotics. Candida and Enterococcus spp. were common. Patients at highest risk for infection were previously treated with antibiotics and those transferred from outside institutions.

Duration of antibiotic treatment after endoscopic ultrasound-guided drainage of walled-off pancreatic necrosis not affecting outcomes.

BACKGROUND AND AIM: Although society guidelines recommend a short course of antibiotics after drainage of walled-off necrosis (WON), the exact duration is unclear. METHODS: This is a retrospective review of patients with no prior antibiotic exposure who underwent dual-modality drainage (DMD) for sterile WON from 2008 to 2017. Patients were grouped into short duration (SD, ≤5 days) versus long duration (LD, >5 days). The main outcome was the frequency of recurrent infections. RESULTS: Sixty-one patients (25 in the SD group and 36 in the LD group) were included. Patients in the two groups had comparable age, comorbidities, and severity of disease (P = 0.89). Patients in the SD group were treated with antibiotics for a median of 3 days compared with 8.5 days in the LD group. There were no differences in recurrent febrile episodes within 30 days of procedure-44% of SD group versus 39% of LD (P = 0.69). There was also no difference in time to resolution of WON (64 days for both groups, P = 0.72) or duration of hospitalization post-DMD (SD 7.7 days versus LD 7.5 days, P = 0.42). Three cases of Clostridium difficile colitis were observed in the LD group. CONCLUSIONS: Longer course of antibiotics seems to have similar outcomes compared with shorter courses in patients with WON treated with DMD. Prolonged-course therapy may predispose to secondary infections like C. difficile colitis. A randomized controlled trial is needed to evaluate the role and duration of peri-procedural antibiotics after drainage of sterile WON.

Pulsatile Varicose Veins Secondary to Severe Tricuspid Regurgitation: Report of a Case Successfully Managed by Endovenous Laser Treatment.

We report a case of pulsatile varicose veins successfully managed by endovenous laser treatment (EVLT) of the great saphenous vein (GSV). A 77-year-old woman taking an anticoagulant was transferred to our hospital for pulsatile varicose veins complicated with repeated venous bleeding from an ulcer of her left lower leg. Doppler echocardiography showed severe tricuspid regurgitation, and duplex ultrasonography revealed an arterial-like pulsating flow in the saphenofemoral junction and along the GSV, but an arteriovenous fistula, obstruction of the deep veins, and the distal incompetent perforators were not detected. Because of a significant bleeding risk due to elevated venous pressure and anticoagulant therapy, EVLT was performed for the GSV, which resulted in the complete occlusion of the GSV and healing of the ulcer. EVLT presents a safe and useful therapeutic technique for pulsatile varicose veins in the limbs.

Association of Appropriate Empirical Antimicrobial Therapy With In-Hospital Mortality in Patients With Bloodstream Infections in the US.

Importance: Bloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy. Objective: To estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality. Design, Setting, and Participants: This retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis. Exposures: Appropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected. Main Outcomes and Measures: Multilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species. Results: Among 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]). Conclusions and Relevance: In this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

Oral vancomycin may have significant absorption in patients with Clostridium difficile colitis.

A patient on haemodialysis with bowel ischemia was given vancomycin 500 mg orally every 6 h for superimposed Clostridium difficile colitis resulting in a high vancomycin serum concentration. When treating C. difficile colitis in patients with significant renal impairment and bowel injury, we recommend administering the lower dose of oral vancomycin.

Carbapenem susceptibility patterns for clinical isolates of Mycobacterium abscessus determined by the Etest method.

Mycobacterium abscessus is resistant to multiple antibiotics, creating treatment challenges. Carbapenems are tested to increase therapeutic alternatives. We performed in vitro susceptibility testing by Etest of four carbapenems for M. abscessus isolates. Imipenem demonstrated the most in vitro activity, and testing of other carbapenems provided no additional value.

Mycobacterium neoaurum and Mycobacterium bacteremicum sp. nov. as causes of mycobacteremia.

Reference isolates of Mycobacterium neoaurum, Mycobacterium aurum, and the nonvalidated species "Mycobacterium lacticola" were the focus of two recent molecular taxonomic studies. On the basis of this grouping, we identified 46 clinical pigmented, rapidly growing mycobacterial isolates. By 16S rRNA gene sequencing, only two major taxa were identified: M. neoaurum and a previously uncharacterized "M. neoaurum-like" group. The M. neoaurum-like group exhibited only 99.7% identity to M. neoaurum by 16S rRNA gene sequencing and 96.5% identity to M. neoaurum by rpoB sequencing and was named M. bacteremicum. No clinical isolates of M. aurum or M. lacticola were identified. Of isolates with known sources, 4/8 (50%) of M. bacteremicum isolates and 22/34 (65%) of M. neoaurum isolates were recovered from blood, and 35% of these were known to be from patients with catheter-related sepsis. MIC and clinical data on these 46 isolates of M. neoaurum and M. bacteremicum along with a review of 16 previously reported cases of infection with the M. neoaurum-M. lacticola group demonstrated that the isolates were highly susceptible to all drugs tested except clarithromycin, and most clinical cases were successfully treated. The clarithromycin resistance suggested the presence of an inducible erm gene reported in other species of rapidly growing mycobacteria. Sequencing studies are currently required to identify these two species. Strain ATCC 25791 (originally submitted as an example of Mycobacterium aurum) is proposed to be the type strain of M. bacteremicum.

Staphylococcus aureus bacteriuria as a prognosticator for outcome of Staphylococcus aureus bacteremia: a case-control study.

BACKGROUND: When Staphylococcus aureus is isolated in urine, it is thought to usually represent hematogenous spread. Because such spread might have special clinical significance, we evaluated predictors and outcomes of S. aureus bacteriuria among patients with S. aureus bacteremia. METHODS: A case-control study was performed at John H. Stroger Jr. Hospital of Cook County among adult inpatients during January 2002-December 2006. Cases and controls had positive and negative urine cultures, respectively, for S. aureus, within 72 hours of positive blood culture for S. aureus. Controls were sampled randomly in a 1:4 ratio. Univariate and multivariable logistic regression analyses were done. RESULTS: Overall, 59% of patients were African-American, 12% died, 56% of infections had community-onset infections, and 58% were infected with methicillin-susceptible S. aureus (MSSA). Among 61 cases and 247 controls, predictors of S. aureus bacteriuria on multivariate analysis were urological surgery (OR = 3.4, p = 0.06) and genitourinary infection (OR = 9.2, p = 0.002). Among patients who died, there were significantly more patients with bacteriuria than among patients who survived (39% vs. 17%; p = 0.002). In multiple Cox regression analysis, death risks in bacteremic patients were bacteriuria (hazard ratio 2.9, CI 1.4-5.9, p = 0.004), bladder catheter use (2.0, 1.0-4.0, p = 0.06), and Charlson score (1.1, 1.1-1.3, p = 0.02). Neither length of stay nor methicillin-resistant Staphylococcus aureus (MRSA) infection was a predictor of S. aureus bacteriuria or death. CONCLUSIONS: Among patients with S. aureus bacteremia, those with S. aureus bacteriuria had 3-fold higher mortality than those without bacteriuria, even after adjustment for comorbidities. Bacteriuria may identify patients with more severe bacteremia, who are at risk of worse outcomes.

Classic pyomyositis of the extremities as an unusual manifestation of Blastomyces dermatitidis: a report of two cases.

Pyomyositis is an infection of skeletal muscle that, by definition, arises intramuscularly rather than secondarily from adjacent infection. It is usually associated with bacterial infection, particularly Staphylcococcus aureus. Fungi are rare causes, and Blastomyces dermatitidis has not been reported previously. In this case series, we report two cases of pyomyositis caused by B. dermatitidis. Cases were prospectively identified through routine clinical care at a single academic referral hospital. Two patients with complaints of muscle pain and subacute cough were treated at our hospital in 2007. Both patients were found to have pyomyositis caused by B. dermatitidis- in the quadriceps muscles in one patient, and in the calf muscle in another - by radiological imaging and fungal culture. Both were also diagnosed with pneumonia caused by B. dermatitidis (presumptive in one, confirmed in the other). There was no evidence of infection of adjacent structures, suggesting that the route of infection was likely direct haematogenous seeding of the muscle. A review of the literature confirmed that although B. dermatitidis has been described as causing axial muscle infection secondary to adjacent infection such as vertebral osteomyelitis, our description of isolated muscle involvement (classic pyomyositis) caused by B. dermatitidis, particularly of the extremity muscles, is unique. We conclude that B. dermatitidis is a potential cause of classic pyomyositis.

Noninvasive Technique for Measuring Central Venous and Arterial Pressure Using Controlled Compression Sonography.

Objective: Devices that can noninvasively measure central and peripheral venous pressures with relative ease and in a short time were developed, but the resolution of the data that can be recorded with these devices is limited to 50 mmHg. Materials and Methods: We aimed to develop a system that could overcome this limitation. We used an innovative noninvasive controlled compression sonography device that could theoretically measure pressures higher than 200 mmHg. First, to validate the accuracy of our device, an in vitro study was conducted. Then, the values measured by our system were compared to conventionally obtained measurements of central venous, peripheral venous, and brachial artery pressures. Finally, regression analyses were used to determine the correlations between measurements obtained from different devices. Results: With our device, the measurement of venous and arterial pressures required only 3 to 15 sec. All regression analyses revealed a significant statistical correlation between measurements, although the correlation coefficient was relatively low for arterial pressure. Conclusion: For venous pressure, our system can provide measurements that could not be measured noninvasively with conventional methods. Regarding arterial pressure, although our system could measure systolic pressure, further studies are needed to confirm the clinical efficacy of our device.

Prediction of Postoperative Cerebral Infarction after Cardiovascular Surgery Using Quantitative Measurement of Cerebral Blood Flow with Brain Single-Photon Emission Computed Tomography.

Prediction of postoperative cerebral infarction after cardiovascular surgery is difficult. The present study investigated whether quantitative evaluation of preoperative cerebral blood flow used in the Japanese EC-IC Bypass Trial (JET) study is useful for the prediction of postoperative cerebral infarction after cardiovascular surgery. First, patients were divided into two groups based on preoperative cerebral blood flow. In an evaluation using preoperative imaging, patients with good or mildly decreased preoperative cerebral blood flow, divided into clinical stage I or II by quantitative evaluation showed no postoperative cerebral infarction. However, 24% of patients with poor cerebral blood flow who were categorized as clinical stage II, experienced postoperative cerebral infarction. The incidence rate was not statistically significantly different when the groups were compared. Second, patients were divided into two groups based on the anatomical area of the brain affected corresponding to clinical stage II. Patients with a 10% and greater brain involvement had a significantly higher incidence of postoperative cerebral infarction (38%) compared to others (0%, p<0.01). This method may be useful for the prediction of postoperative cerebral infarction after cardiovascular surgery, but a further prospective study is needed. (This is a translation of J Jpn Coll Angiol 2017; 57: 125-133.).

Embolic myocardial infarction and left ventricular rupture due to mitral valve endocarditis.

A left ventricular rupture due to embolic myocardial infarction is extremely rare. A 72-year-old woman developed an acute embolic myocardial infarction and mitral regurgitation due to infective endocarditis. Two days after the infarction, a left ventricular free wall rupture occurred after transesophageal echo examination. She received an epicardial patch and mitral valve replacement. Perioperatively, an intra-aortic balloon pump and long-term antibiotics were used. The postoperative course was uneventful, and she is doing well 10 months after surgery.

Effects of supplemental sialyl Lewis(x) analogue during warm blood cardioplegia.

Effects of supplemental Sialyl Lewisx analogue, a major ligand for all three selectin family members, during warm blood cardioplegia were assessed in the blood perfused isolated rat heart. The isolated hearts were arrested for 60 min with warm blood cardioplegia given at 20-min intervals. This was followed by 60 min of reperfusion. The hearts were divided into the following two groups according to the supplemental drugs added to the cardioplegic solution. The control group (n = 6) received standard warm blood cardioplegia. The Sialyl Lewisx analogue group (n = 6) received warm blood cardioplegia supplemented with Sialyl Lewisx analogue (60 micrograms/ml). Cardiac function, endothelial function, myocardial metabolism and myocardial myeloperoxidase activity were assessed before and after cardioplegic arrest. Left ventricular developed pressure and dp/dt were significantly (p < 0.05) greater and -dp/dt was significantly (p < 0.05) lower in the Sialyl Lewisx analogue group than the control group during reperfusion. Coronary flow at 15 min of reperfusion and NO production, when acetylcholine chloride was added were significantly (p < 0.05) greater in the Sialyl Lewisx analogue group than the control group. Myeloperoxidase activity was significantly (p < 0.05) lower in the Sialyl Lewisx analogue group than the control group. The results suggest that selectin-mediated endothelial-leukocyte interactions may play an important role in myocardial ischemia and reperfusion injury. Supplementation of Sialyl Lewisx analogue during warm blood cardioplegia may provide superior myocardial protection by suppressing leukocyte-endothelial interaction during early reperfusion period.

Surgical treatment of abdominal aortic aneurysm associated with horseshoe kidney: symphysiotomy using harmonic focus.

Coexistence of horseshoe kidney and abdominal aortic aneurysm (AAA) is a rare entity that presents a technical challenge to vascular surgeons. How to approach such an AAA with horseshoe kidney and whether to divide the renal isthmus remains a controversial issue. We report here the successful surgical repair of an AAA with horseshoe kidney via the transperitoneal approach with division of the renal isthmus by Harmonic Focus, which allowed easy division of the isthmus without bleeding. Harmonic Focus, a hand-held type of harmonic scalpel, was thus useful in symphysiotomy of the horseshoe kidney.

Intravenous colistin-induced acute respiratory failure: A case report and a review of literature.

The emergence of multi-drug-resistant gram negative bacillary infections has regained popularity of ancient drugs such as polymyxins. We report a case of acute respiratory failure induced by use of intravenous colistimethate, which is one of the forms of polymyxin. The patient is a 31 year old female with paraplegia due to spina bifida who underwent excisional debridement of large lumbosacral decubitus ulcer with osteomyelitis infected with pan-resistant Pseudomonas aeruginosa and MRSA. Six days after initiation of intravenous colistimethate and vancomycin, she developed acute respiratory failure requiring mechanical ventilation. Pan-culture was negative including a chest radiograph. V/Q scan showed low probability for pulmonary embolism. Echocardiogram showed normal right ventricle with no strain or pulmonary hypertension. Colistimethate was discontinued. Within 24 hours, she was extubated. In the early years after introduction of polymyxin, there were several reports of acute respiratory paralysis. The mechanism is thought to be noncompetitive myoneuronal presynaptic blockade of acetylcholine release. Though a direct causal relationship for respiratory failure is often difficult to establish in current era with multiple co morbidities, the timeframe of apnea, acuity of onset as well as rapid recovery in our case clearly point out the causal relationship. In addition, our patient also developed acute renal failure, presumably due to colistimethate induced nephrotoxicity, a possible contributing factor for her acute respiratory failure. In summary, colistimethate can induce acute neurotoxicity including respiratory muscular weakness and acute respiratory failure. Clinicians should consider its toxicity in the differential diagnosis of acute respiratory failure especially in critically ill patients.

Anastomosis of left to right superior vena cava for repair of unroofed coronary sinus.

Left superior vena cava (LSVC) draining into the left atrium is a rare congenital cardiac complex. It may appear as an isolated anomaly or as part of more complex cardiac anomalies. Intraatrial rerouting techniques have been the most common approaches to correcting LSVC drainage into the left atrium in patients without a connecting vein. Although these techniques have proved reliable and successful, there are cases in which extracardiac methods for managing this form of anomalous systemic drainage may be preferable. In the present report, we describe an extracardiac approach to the correction of LSVC draining into the left atrium.

A foot ulcer caused by the use of an angio-seal arterial closure device after percutaneous transluminal angioplasty: a case report.

Although the Angio-Seal arterial closure device is widely used for preventing bleeding and facilitating early ambulation after arterial puncture, it is also associated with unique complications, such as stenosis, occlusion, or peripheral embolism. We report the first case of a foot ulcer that developed 70 days after an Angio-Seal application. The collagen sponge component accidently positioned itself in the arterial lumen and was not absorbed. A foreign body reaction was observed microscopically. In patients with arteriosclerosis, the Angio-Seal device should be used carefully; post procedural monitoring is necessary after implantation.