Understanding the potential impact of different drug properties on SARS-CoV-2 transmission and disease burden : a modelling analysis

Q1Q1Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in highincome countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priorityRevista Internacional - Indexad

Undiagnosed Cryptococcus gattii meningitis leading to subsequent ventriculoperitoneal shunt infection in a patient with symptoms of normal pressure hydrocephalus: case report and literature review

Abstract Background Cryptococcus gattii is known to be an etiologic agent of human cryptococcosis, particularly in immunocompetent persons. C. gattii infection usually involves the central nervous system, the respiratory tract, or may be disseminated. Here we report an atypical manifestation of C. gattii infection in a patient who had C. gattii meningitis complicating the ventriculoperitoneal (VP) shunt infection and concurrent infected intraabdominal VP shunt pseudocyst. Case presentation A 66-year-old Thai female was initially diagnosed with normal pressure hydrocephalus (NPH) and underwent programmable VP shunt placement. However, she still suffered from recurrent communicating hydrocephalus with in-place VP shunt, and later developed recurrent gait impairment, chronic abdominal pain and abdominal mass. Radiological studies demonstrated recurrent hydrocephalus and a very large intraabdominal VP shunt pseudocyst. C. gattii was isolated from both the cerebrospinal fluid and the pseudocyst aspiration. C. gattii meningitis complicating the VP shunt infection and concurrent infected intraabdominal VP shunt pseudocyst was diagnosed. Prolonged antifungal therapy, removal of the infected VP shunt with subsequent implant of a new shunt provided a good outcome. Conclusion Chronic C. gattii meningitis should be aware in a patient presenting with normal pressure hydrocephalus. Under-diagnosed cryptococcal meningitis following VP shunt insertion for treating the hydrocephalus can render a complicated VP shunt infection including infected VP shunt pseudocyst

Distinguishing clinical characteristics of central nervous system tuberculosis in immunodeficient and non-immunodeficient individuals: a 12-year retrospective study

Abstract Background Central nervous system tuberculosis (CNS TB) is a severe Mycobacterium tuberculosis (MTB) infection. It is unclear whether a patient’s immune status alters the clinical manifestations and treatment outcomes of CNS TB. Methods Between January 2007–December 2018, chart reviews of CNS TB, including tuberculous meningitis (TBM), tuberculoma/abscess, and TB myelitis, were made. Subjects were categorized as immunodeficient (ID) and non-immunodeficient (NID). Results Of 310 subjects, 160 (51.6%) were in the ID group—132 (42.6%) had HIV and 28 (9.0%) had another ID, and 150 (48.4%) were in the NID group. The mean age was 43.64 ± 16.76 years, and 188 (60.6%) were male. There were 285 (91.9%) TBM, 16 (5.2%) tuberculoma/abscess, and 9 (2.9%) myelitis cases. The TBM characteristics in the ID group were younger age (p = 0.003), deep subcortical location of tuberculoma (p = 0.030), lower hemoglobin level (p < 0.001), and lower peripheral white blood cell count (p < 0.001). Only HIV individuals with TBM had an infection by multidrug-resistant MTB (p = 0.013). TBM mortality was varied by immune status —HIV 22.8%, other ID 29.6%, and NID 14.8% (p < 0.001). Factors significantly associated with unfavorable outcomes in TBM also differed between the HIV and NID groups. Conclusions TBM is the most significant proportion of CNS TB. Some of the clinical characteristics of TBM, such as age, radiographic findings, hematological derangement, and mortality, including factors associated with unfavorable outcomes, differed between ID and non-ID patients

Lomentospora prolificans vertebral osteomyelitis with spinal epidural abscess in an immunocompetent woman: Case report and literature review

Lomentospora prolificans is a rare cause of vertebral osteomyelitis. We report a case of L. prolificans thoracic vertebral osteomyelitis with spinal epidural abscess in a patient without apparent immunodeficiency. Clinical manifestations and radiographic findings could not distinguish from other etiologic agents. Treatment is also challenging because L. prolificans is usually resistant to antifungal agents. The patient underwent surgical debridement and has been receiving a prolonged combination of antifungal therapy to prevent an infection relapse. Keywords: Lomentospora prolificans, Vertebral osteomyelitis, Spinal epidural abscess, Immunocompetent patien

Additional file 1: Table S1. of Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection

(Clinical features and outcomes of 11 non-tuberculous mycobacterial and 5 tuberculous prosthetic joint infections). (DOC 67 kb

Demographics and clinical characteristics of patients with extensively drug-resistant <i>Pseudomonas aeruginosa</i> (XDR-PA) and non-XDR-PA infection.

<p>Demographics and clinical characteristics of patients with extensively drug-resistant <i>Pseudomonas aeruginosa</i> (XDR-PA) and non-XDR-PA infection.</p

Treatment, and clinical and microbiological outcomes, of patients with <i>Pseudomonas aeruginosa</i> infections.

<p>Treatment, and clinical and microbiological outcomes, of patients with <i>Pseudomonas aeruginosa</i> infections.</p

Independent predictors of mortality attributable to infection.

<p>Independent predictors of mortality attributable to infection.</p

Epidemiology and risk factors of extensively drug-resistant <i>Pseudomonas aeruginosa</i> infections

<div><p>Background</p><p>The incidence of nosocomial infections from extensively drug-resistant <i>Pseudomonas aeruginosa</i> (XDR-PA) has been increasing worldwide. We investigated the prevalence and factors associated with XDR-PA infections, including the factors that predict mortality.</p><p>Methods</p><p>We retrospectively studied a cohort of adult, hospitalized patients with <i>P</i>. <i>aeruginosa</i> (PA) infections between April and December 2014.</p><p>Results</p><p>Of the 255 patients with PA infections, 56 (22%) were due to XDR-PA, 32 (12.5%) to multidrug resistant <i>Pseudomonas aeruginosa</i> (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).</p><p>Conclusion</p><p>The prevalence of XDR-PA infections represented almost a quarter of <i>Pseudomonas aeruginosa</i> 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.</p></div

Independent predictors of XDR-PA infections.

<p>Independent predictors of XDR-PA infections.</p