Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. METHODS AND FINDINGS: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. CONCLUSION: In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04425382.

Stroke in Qatar: a first prospective hospital-based study of acute stroke.

BACKGROUND: Stroke is a major cause of morbidity and mortality in Qatar. OBJECTIVES: The aim of our study was to determine types of strokes, the associated risk factors, clinical presentation, outcome, and time to hospital admission among Qatari and non-Qatari patients as well as young and nonyoung patients. METHODS: We conducted a hospital-based prospective observational study including all patients admitted to Hamad Medical Corporation with first-ever stroke from September 15, 2004, to September 14, 2005. A stroke was defined according to World Health Organization criteria. RESULTS: Stroke was confirmed in 270 patients of whom 217 (80.4%) had ischemic stroke and 53 (19.6%) had hemorrhagic stroke. Male patients predominated in all types of stroke. The main risk factors for stroke were hypertension and diabetes, whereas lacunar infarct was the most common subtype of ischemic stroke. Risk factor profiles were similar between Qatari and non-Qatari patients except for hypercholesterolemia, which was observed with a higher frequency in Qatari compared with non-Qatari patients with ischemic stroke. There were significant differences between the young and nonyoung patients with ischemic stroke with respect to risk factors, ejection fraction, ventricular wall-motion abnormalities, time to hospital admission, and outcome. Most patients arrived at the hospital more than 3 hours from stroke onset because of unawareness of stroke symptoms. The overall in-hospital mortality was 9.3%. CONCLUSIONS: Hypertension and diabetes mellitus were the main risk factors for stroke in Qatar, whereas lacunar infarct was the most common subtype. Significant differences between the young and nonyoung patients were observed with respect to risk factors, ejection fraction, ventricular wall-motion abnormalities, time to hospital admission, and outcome.

Epidemiological and Clinical Features of Salmonella Typhi Infection Among Adult Patients in Qatar: A Hospital-based Study.

OBJECTIVES: We sought to describe the epidemiological and clinical features of typhoid fever in Qatar. METHODS: We conducted a retrospective study of adult patients treated for typhoid fever at Hamad General Hospital and Alkhor Hospital between 2005 and 2012. RESULTS: The mean age of the 354 patients enrolled in the study was 28.4±9.3 years; 296 (83.6%) were males. There were 42, 48, 39, 44, 46, 47, 52, and 36 cases of adults with typhoid fever in 2005, 2006, 2007, 2008, 2009, 2010, 2011, and 2012, respectively. Overall, 343 (96.9%) patients had a history of travel to endemic areas. Among them, 93.0% acquired typhoid fever in the Indian subcontinent. Fever was observed in all cases, and the other predominant symptoms were abdominal pain (38.1%), diarrhea (35.6%), and headache (33.1%). Salmonella typhi, showed high resistance to ciprofloxacin (n = 163; 46.0%), and low resistance to ceftriaxone (n = 2; 0.6%). Four patients developed intestinal perforation, which was surgically repaired in two cases. Two patients (0.6%) died. CONCLUSIONS: Typhoid fever was frequent among immigrants to endemic areas. Travelers returning from endemic areas with suspected typhoid fever should be treated empirically with third-generation cephalosporin after obtaining appropriate cultures. Moreover, preventive measurements such as education on food and water hygiene, and effective vaccination of travelers should be practiced widely among travelers to endemic areas to reduce morbidity and mortality.

Acute Bacterial Meningitis in Qatar: A Hospital-Based Study from 2009 to 2013.

BACKGROUND AND OBJECTIVES: Bacterial meningitis is a common medical condition in Qatar. The aim of this study was to describe the clinical characteristics of bacterial meningitis, the frequency of each pathogen, and its sensitivity to antibiotics and risk factors for death. PATIENTS AND METHODS: This retrospective study was conducted at Hamad General Hospital between January 1, 2009, and December 31, 2013. RESULTS: We identified 117 episodes of acute bacterial meningitis in 110 patients. Their mean age was 26.4 ± 22.3 years (range: 2-74) and 81 (69.2%) of them were male patients. Fifty-nine episodes (50.4%) were community-acquired infection and fever was the most frequent symptom (94%), whereas neurosurgery is the most common underlying condition. Coagulase-negative staphylococci were the most common causative agent, of which 95% were oxacillin-resistant, while 63.3% of Acinetobacter spp. showed resistance to meropenem. The in-hospital mortality was 14 (12%). Only the presence of underlying diseases, hypotension, and inappropriate treatment were found to be independent predictors of mortality. CONCLUSION: Acute bacterial meningitis predominantly affected adults and coagulase-negative staphylococci species were the common causative agent in Qatar with majority of infections occurring nosocomially. More than 90% of all implicated coagulase-negative staphylococci strains were oxacillin-resistant.

Characteristics of patients with definite septic arthritis at Hamad General Hospital, Qatar: a hospital-based study from 2006 to 2011.

The aim of this retrospective study was to determine the epidemiological and clinical characteristics, coexisting conditions, causative organisms, and outcomes of all adult patients 15 years of age or older who had definite septic arthritis at Hamad General Hospital, Qatar, from 2006 to 2011. During this period, 56 patients were diagnosed with septic arthritis (mean age ± SD, 49.0 ± 16.6 years). In 53 of 56 (94.6%) patients, arthritis was diagnosed in a single joint, while polyarthritis was diagnosed in 3 of 56 (5.4%) patients; the most commonly involved joint was the knee (40 of 59 joints, 67.7%). The most frequent coexisting condition was diabetes mellitus (24 of 56 patients, 42.8%). Joint pain and restriction of movement were reported by all patients. Gram-positive bacteria accounted for 36 of all 57 (63.0%) isolated microorganisms, and Staphylococcus aureus was the most common pathogen (20 of 57 microorganisms, 35.0%). Three cases of tuberculous arthritis were seen. The most favored antibiotic combinations were cloxacillin/ciprofloxacin, cefazolin/ciprofloxacin, and vancomycin/ciprofloxacin. Repeated needle aspiration, open joint drainage, and arthroscopic techniques were performed in 18 (32.1%), 22 (39.3%), and 11 (19.6%) of the 56 patients, respectively. The 30-day mortality was 3.6%, and the remaining patients showed clinical improvement upon discharge. In conclusion, there was no specific sign or symptom for diagnosing septic arthritis. Isolation of bacteria from the synovial fluid confirmed the diagnosis, and S. aureus and streptococci were the most common pathogens isolated. Prompt treatment with appropriate antibiotics and synovial drainage are mandatory to improve the outcome.

Epidemiological features of Clostridium difficile infection among inpatients at Hamad General Hospital in the state of Qatar, 2006-2009.

The aim of this retrospective study was to evaluate the epidemiology, clinical course and outcome of Clostridium difficile infection among inpatients at Hamad General Hospital in Qatar, from 2006 to 2009. During this period, 123 patients were diagnosed with C. difficile infection and the overall incidence was 1.6/10,000 patient days. The mean age (±SD) of patients was 50.9 ± 21.2 years. The most frequent underlying disease was hypertension 51/123 (41.5%) and 133 prescriptions of antimicrobials were ordered for 105/123 (86.1%) patients prior to C. difficile infection with piperacillin-tazobactam being the most frequently prescribed antimicrobial 39/131 (29.7%). Nosocomial infection was found in 101/123 (82.0%) of cases, and the most common clinical feature was watery diarrhoea 119/123 (96.7%). Antimicrobials were discontinued in 53/105 (50.5%) cases and 118/123 (95.9%) of them received metronidazole as the initial treatment. The mean treatment duration (±SD) was 9.08 ± 5.6 days. Fifteen (12.7%) patients failed the first course of antimicrobial therapy, of which four were treated with oral vancomycin, and eleven patients received both drugs. Recurrence of infection was observed in 12/118 (10.2%) patients and 30-day mortality was 38/123 (30.9%). Several clinical variables were associated with increased 30-day mortality on univariate analysis. Only occurrence of disease among Qataris, prolonged hospitalisation, positive stool occult blood test, high white blood cells and septic shock were found to be independent predictors of mortality by multivariate logistic regression analysis. In conclusion, C. difficile infection was a recognise cause of morbidity and mortality in our hospital with low and stable incidence. It involved predominantly patients younger than 65 years with underlying illness and metronidazole and vancomycin were effective in resolving symptoms in the majority of our patients.

Fungal peritonitis in patients undergoing continuous ambulatory peritoneal dialysis in Qatar.

INTRODUCTION: This study was conducted at Hamad General Hospital to determine the incidence of fungal peritonitis and to describe its clinical and microbiological findings in patients undergoing continuous ambulatory peritoneal dialysis in Qatar. METHODOLOGY: The medical records of these patients between 1 January 2005 and 31 December 2008 were retrospectively reviewed and the collected data were analysed. RESULTS: During the study period, 141 episodes of peritonitis were observed among 294 patients. In 14 of these episodes (9.9%), fungal peritonitis was reported in 14 patients with a rate of 0.05 episodes per patient year, while the bacterial peritonitis rate was 0.63 per patient year. Thirteen (93%) patients had one or more previous episodes of bacterial peritonitis that was treated with multiple broad-spectrum antibiotics, 11 (85%) had received broad-spectrum antibiotics within the preceding month, 12 (92%) within three months, and 8 (62%) within six months. Candida species were the only fungal species isolated from the dialysate with predominance of non-albicans Candida species (especially Candida parapsilosis). Therapeutic approach was immediate catheter removal, followed by systemic antifungal therapy and temporary haemodialysis. Nine patients (64.3%) were continued on haemodialysis, whereas five patients (35.7%) died. CONCLUSIONS: Prior antibiotic use was an important risk factor predisposing patients to the development of fungal peritonitis. Early detection of fungal peritonitis would lead to early institution of appropriate therapy and prevention of complications.

Epidemiology of bacteraemia in Hamad general hospital, Qatar: a one year hospital-based study.

We conducted a one-year observational study from July 2007 to June 2008 to describe the epidemiology of bacteraemia at Hamad general hospital. During this period, a total of 452 episodes of bacteraemia occurred, which corresponds to a rate of 19/1000 hospital admissions. Most patients 58.8% (266/452) had community acquired bacteraemia, and primary bacteraemia accounted for 62.2% (281/452) of the cases. The most common source of bacteraemia was intravenous catheterization in 19.2% (87/452) but no source was identified in 42.9% (194/452) of the episodes. Gram-negative organisms were isolated in 63.1% (285/452) episodes with Escherichia coli being the most frequent 21.5% (97/452). Multidrug resistance was observed in 33.3% (7/21) of all Pseudomonas aeruginosa isolates, 50% (6/12) of Acinetobacter isolates and 28.6% (6/21) of Enterobacter isolates, whereas all ESBL producing Klebsiella spp. and E. coli were multiresistant. The percentages of oxacillin resistant coagulase negative Staphylococci isolates and methicillin-resistant Staphylococcus aureus isolates were 81.8% (27/33) and 13.2% (7/53) respectively. In hospital mortality was 22.5% (102/452), and inadequate treatment and septic shock were found to be independent predictors of mortality. Therefore, bloodstream infection surveillance is crucial to produce meaningful guidelines for prevention (e.g., catheter-related) and empirical treatment of bacteraemia in Qatar.

Herpes simplex virus type 2 (Mollaret's) meningitis: a case report.

INTRODUCTION: Mollaret's meningitis is an unusual and under-appreciated syndrome of benign, recurrent aseptic meningitis. The available literature indicates that the causative agent is herpes simplex virus type 2 (HSV-2) in the majority of cases and much less frequently herpes simplex virus type 1 (HSV-1). CASE REPORT: We report the case of a 49-year-old Indian female who had four attacks of recurrent lymphocytic meningitis (Mollaret's meningitis) occurring over a 7-year period. The diagnosis of herpes simplex meningitis was made at the time of the fourth episode by a positive PCR for herpes simplex virus infection in the cerebrospinal fluid. During the first three episodes, the patient was treated with anti-tuberculous drugs and antibiotics for bacterial meningitis; however for the last episode, once the diagnosis of herpes simplex meningitis was confirmed, only symptomatic treatment was given. No long-term suppressive therapy was given and no recurrence has been experienced so far. CONCLUSIONS: Mollaret's meningitis should be suspected in all cases of recurrent lymphocytic meningitis. Early diagnosis may prevent prolonged hospital admissions, unnecessary investigations, and exposure to unnecessary medications, with the associated considerable costs. Treatment with acyclovir may be beneficial in decreasing the severity and duration of attacks and in preventing further episodes. [Au?1].

Myocardial abscess and bacteremia complicating Mycobacterium fortuitum pacemaker infection: case report and review of the literature.

A case of pacemaker infection complicated by bacteremia and myocardial abscess caused by Mycobacterium fortuitum is reported and 9 other cases of pacemaker infection associated with rapidly growing mycobacteria are reviewed. Most cases developed within 6 months from implantation suggesting nosocomial acquisition. Wound discharge, fever, and pain at generator site were the most common presenting features. At presentation they had a median duration of symptoms of 34 days. Concomitant bacteremia was present in half of the cases. Antibiotics therapy and removal of the pacemaker system were needed to achieve cure in the majority of cases. Clarithromycin and fluoroquinolones were the most commonly used antibiotics.

Strongyloides stercoralis hyperinfection after corticosteroid therapy: a report of two cases.

Two cases of Strongyloides stercoralis hyperinfection are described. Both patients were expatriates from the Indian subcontinent, and reported the use of corticosteroids. The first patient presented with severe pulmonary disease that necessitated respiratory support, followed by acute abdomen and intestinal obstruction and he succumbed to these diseases. The second patient also presented with acute pulmonary disease, which responded to antihelmintic treatment and supportive care; however, he died later due to his primary disease. The clinical features of S stercoralis hyperinfection are nonspecific; therefore, a high index of suspicion is required for early diagnosis and to start appropriate therapy. Because of the seriousness of the disease and the associated high mortality we suggest screening for S stercoralis in patients from endemic areas who will be taking immunosuppressive therapy.