Real-World Effectiveness and Optimal Dosage of Favipiravir for Treatment of COVID-19: Results from a Multicenter Observational Study in Thailand.

Favipiravir is a broad-spectrum oral antiviral agent that shows in vitro activity against SARS-CoV-2. Presently, data on the real-world effectiveness and optimal dosage of favipiravir for treating COVID-19 are limited. We conducted a retrospective observational study of hospitalized adult patients with COVID-19 at five tertiary care hospitals in Thailand. We reviewed patient charts to obtain all necessary data. Among 247 COVID-19 patients, 63 (23.0%) received ≥1 dose of favipiravir. Of these 63 patients, 61.9% were male with a median age of 48 years (range 22-85 years), 27.0% required an O2 nasal cannula, 9.5% required non-invasive ventilation and/or high-flow O2 therapy, and 6.4% required invasive mechanical ventilation and/or ECMO. The median baseline NEWS2 score was 5 (0-16). The Day-7 clinical improvement rate [95%CI] was 66.7% [53.7-78.0%] in all patients, 92.5% [75.7-99.1%] in patients who did not require O2 supplementation, and 47.2% [0.4-64.5%] in patients who required O2 supplementation. No life-threatening adverse events were identified. The 28-day mortality rate was 4.8%. A multivariate analysis revealed three poor prognostic factors for Day-7 clinical improvement (odds ratio (95%CI); p-value): older age (0.94 (0.89-0.99); p = 0.04), a higher baseline NEWS2 score (0.64 (0.47-0.88); p = 0.006), and a lower favipiravir loading dose (≤45 mg/kg/day) (0.04 (0.005-0.4); p = 0.006). In conclusion, our study reports the promising effectiveness of favipiravir for treating COVID-19 patients. In addition to older age and a high baseline NEWS2 score, a low loading dose of favipiravir (≤45 mg/kg/day) was also identified as a poor prognostic factor for early clinical improvement. Further studies to explore the optimal dose and the optimal timing of drug initiation for favipiravir should be performed.

Efficient ZFN-Mediated Stop Codon Integration into the CCR5 Locus in Hematopoietic Stem Cells: A Possible Source for Intrabone Marrow Cell Transplantation.

We reported a simple genome editing approach that can generate human immunodeficiency virus-1 (HIV) coreceptor defective cells, which may be useful for latent viral eradication treatment. Samples of bone marrow leftover after diagnostic procedures and crude bone marrow from aviremic HIV patients were subjected to zinc finger nuclease-mediated stop codon insertion into chemokine receptor 5 (CCR5) loci. Locked nucleic acid-based polymerase chain reaction was used to estimate the amount of insertion in the expandable CD34+ cells. The results showed that about 0.5% of CD34+ cells carried stop codon insertions in CCR5 loci. Cells edited using this simple protocol have the potential to be infused back into the bone marrow.

Epidemiology and risk factors of extensively drug-resistant Pseudomonas aeruginosa infections.

BACKGROUND: The incidence of nosocomial infections from extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide. We investigated the prevalence and factors associated with XDR-PA infections, including the factors that predict mortality. METHODS: We retrospectively studied a cohort of adult, hospitalized patients with P. aeruginosa (PA) infections between April and December 2014. RESULTS: Of the 255 patients with PA infections, 56 (22%) were due to XDR-PA, 32 (12.5%) to multidrug resistant Pseudomonas aeruginosa (MDR-PA), and 167 (65.5%) to non-MDR PA. Receiving total parenteral nutrition (adjusted OR [aOR] 6.21; 95% CI 1.05-36.70), prior carbapenem use (aOR 4.88; 95% CI 2.36-10.08), and prior fluoroquinolone use (aOR 3.38; 95% CI 1.44-7.97) were independently associated with the XDR-PA infections. All XDR-PA remained susceptible to colistin. Factors associated with mortality attributable to the infections were the presence of sepsis/septic shock (aOR 11.60; 95% CI 4.66-28.82), admission to a medical department (aOR 4.67; 95% CI 1.81-12.06), receiving a central venous catheter (aOR 3.78; 95% CI 1.50-9.57), and XDR-PA infection (aOR 2.73; 95% CI 1.05-7.08). CONCLUSION: The prevalence of XDR-PA infections represented almost a quarter of Pseudomonas aeruginosa hospital-acquired infections and rendered a higher mortality. The prompt administration of an appropriate empirical antibiotic should be considered when an XDR-PA infection is suspected.

NOCARDIA BEIJINGENSIS PSOAS ABSCESS AND SUBCUTANEOUS PHAEOHYPHOMYCOSIS CAUSED BY PHAEOACREMONIUM PARASITICUM IN A RENAL TRANSPLANT RECIPIENT: THE FIRST CASE REPORT IN THAILAND.

We describe the first case of a psoas muscle abscess caused by Nocardia beijingensis and subcutaneous phaeohyphomycosis caused by Phaeoacremonium parasiticum in a renal transplant recipient. The patient was treated for nocardiosis with percutaneous drainage and intravenous trimethoprim/sulfamethoxazole (TMP/SMX) combined with imipenem for 2 weeks, followed by a 4-week course of intravenous TMP/SMX and then oral TMP/SMX. During hospitalization for the psoas muscle abscess the patient developed cellulitis with subcutaneous nodules of his right leg. Skin biopsy and cultures revealed a dematiaceous mold, subsequently identified as P. parasiticum by DNA sequencing. The subcutaneous phaeohyphomycosis was treated with surgical drainage and liposomal amphotericin B for 4 weeks followed by a combination of itraconazole and terbinafine. The patient gradually improved and was discharged home after 18 weeks of hospitalization.

Etiologies and outcomes of pleural effusions in patients with systemic lupus erythematosus.

BACKGROUND: Pleuritis is the most common pulmonary manifestation in systemic lupus erythematosus (SLE). In Thailand, the incidence of tuberculosis (TB) is high; moreover, treatment with immunosuppressive agents increases the risk for TB infection. OBJECTIVE: The objective of this study was to examine the clinical manifestations, etiology, management, and outcomes of patients with SLE and pleural effusion in an area for TB. METHODS: We studied adults satisfying the American College of Rheumatology classification criteria for SLE who presented with pleuritis between 2002 and 2010. Pleuritis was defined as having 1 of 3 of the following criteria: typical pleuritic chest pain, pleural rub, and clinical or radiological evidence of pleural effusion. RESULTS: A total of 119 patients with 127 episodes of pleuritis/pleural effusion were included. Pleuritis was the first presentation in 47 episodes (37%) and was found accompanied with pericarditis for 16%. Most patients (81%) had active SLE in other systems. The causes of pleural effusion included lupus pleuritis (52%), tuberculous pleuritis (9%), parapneumonic effusion (7%), and transudate (15%). The diagnosis was inconclusive in 17%. The diagnosis of lupus pleuritis was made by a clinical diagnosis (47%) and by excluding other causes from pleural fluid analysis or biopsy (53%). Most patients with lupus pleuritic responded well to corticosteroid therapy. CONCLUSIONS: Lupus pleuritis is still the most common cause of pleural effusion in SLE and often reflects its disease activity. The diagnosis of lupus pleuritis is a clinical diagnosis or is performed by excluding other conditions. The treatment outcomes of lupus pleuritis are generally good.

Clinical manifestation, diagnosis, management, and treatment outcome of pericarditis in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the clinical manifestations, diagnosis, etiology, management, and outcomes of patients with systemic lupus erythematosus (SLE) and pericarditis MATERIAL AND METHOD: The authors retrospectively reviewed the records of 81 patients who were diagnosed of SLE according to the American College of Rheumatology criteria and had 82 episodes of pericarditis between 2002 and 2010. The diagnosis of pericarditis was defined as the presence of pericardial effusion alone by echocardiography or having 2 out of 4 of the following criteria: retrosternal pain, pericardial friction rub, widespread ST-segment elevation, and new/worsening pericardial effusion. RESULTS: Most of them (92%) were female with the median disease duration (range) of 1 (0-312) month. Cardiac tamponade occurred in 16% (95% CI 8.72-25.58%). There was no statistically significant difference between patients who developed tamponade and those who did not. The causes ofpericarditis included active SLE (93%), and suspected tuberculosis (TB) (5%), with 2% inconclusive. In patients with lupus pericarditis, 71% had other active organ involvement. Most lupus pericarditis patients (79%) had good response to steroid or NSAIDs. Diagnosis of TB pericarditis was made by clinical suspicion without microbiological or pathological evidence. CONCLUSION: In an endemic area of TB, lupus pericarditis was still the most common cause of pericarditis in SLE. Most patients responded well to steroid.