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the authors deserve recognition for calling all of us out on common sense[1]. Still, I would respectfully like to note that the fundamental changes EUCAST decided to introduce into the meaning of the definitions of the susceptibility categories have been made in the 9th edition of their breakpoint tables, published in January, 2019[2]. It was only in the 10th edition of this document, however, that the changes have been implemented completely. I concur with the authors' view that the new definition should have been pointed out by changing the shorthands to be used in the antibiogram reports.

Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extra-intestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002-2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003-2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82%-98%) after TGC (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with CTX-M for ERV. Percent susceptible also varied by global region for CZA (Asia-Pacific lower) and by U.S. region for ERV (South and South-east U.S. lower). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.…

Abstract Background Koulikoro Health District is one of three districts of Mali where the indoor residual spray (IRS) has been implemented from 2008 to 2016. With widespread of resistance to pyrethroid, IRS was shifted from pyrethroid to pirimiphos-methyl from 2014 to 2016. The objective of this study was to assess the added value of IRS to LLINs on the prevalence of parasitaemia and malaria incidence among children under 10 years old. Methods A comparative study was carried out to assess the effects of pirimiphos-methyl based IRS on malaria prevalence and incidence among children from 6 months to 10 years old in selected pyrethroid resistance villages of two health districts in Mali: one where IRS was implemented in combination with LLINs (intervention area) and one with LLINs-only (control area). Two cross-sectional surveys were carried out at the beginning (June) and end of the rainy season (October) to assess seasonal changes in malaria parasitaemia by microscopy. A passive detection case (PCD) was set-up in each study village for 9 months to estimate the incidence of malaria using RDT. Results There was an increase of 220% in malaria prevalence from June to October in the control area (14% to 42%) versus only 53% in the IRS area (9.2% to 13.2%). Thus, the proportional rise in malaria prevalence from the dry to the rainy season in 2016 was 4-times greater in the control area compared to the IRS area. The overall malaria incidence rate was 2.7 per 100 person-months in the IRS area compared with 6.8 per 100 person-month in the control areas. The Log-rank test of Kaplan–Meier survival analysis showed that children living in IRS area remain much longer free from malaria (Hazard ratio (HR) = 0.45, CI 95% 0.37–0.54) than children of the control area (P 

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Tuberculosis (TB) remains the world’s major infectious cause of death. Early diagnosis of TB is essential in guiding treatment, yet 40% of new TB cases are undiagnosed, which fuels transmission (1). TB diagnosis is difficult in immunocompromised patients, children and patients with extra-pulmonary TB, as most current diagnostic tools rely on sputum as the sample of choice. The World Health Organization (WHO) has identified the urgent need for a non-sputum-based TB test, capable of detecting all forms of TB disease, including pulmonary and extra-pulmonary TB, as a critical tool to reach TB control goals (2).

Since its emergence in Wuhan, Hubei Province, China, the Coronavirus Disease 2019 (COVID-19) has continued to spread with an escalating numbers of cases and countries affected. (Dong et al., 2020) To prevent ongoing transmission, effective screening of suspected cases is necessary which enables the early identification and prompt isolation of cases for epidemic containment. These screening measures for testing have been largely guided by the World Health Organization’s (WHO) case definitions (Anon., 2020a), which serves as a valuable epidemiologic tool for public health officials to track the disease and is regularly updated with the changing epidemiology and demographics of the disease.

Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.…

AbstractBackgroundImipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP).MethodsThis was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7–14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7–14 days after completing therapy in the MITT population. ResultsOf 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P 

pneumoniaventilator-associated bacterial pneumoniaantibiotics…

COVD-19solid organ transplantimmune responseorgan donation…

ABSTRACTBackgroundIntegrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus. But evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes.MethodsWe included participants from clinical cohorts in the North American AIDS Cohort Collaboration who initiated their first ART regimen, containing either InSTI (i.e., raltegravir, dolutegravir, and elvitegravir/cobicstat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RD), and hazard ratios (HR) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal diseases, end-stage liver diseases, or death.ResultsOf 15,993 participants, 5,824 (36%) initiated an InSTI-based, and 10,169 (64%) initiated an EFV-based, regimen. During the 6-year follow-up, 440 of the InSTI group and 1,097 of the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% for the InSTI group and 14.3% for the EFV group, corresponding with a RD of 0.3 percentage point (95% CI: -2.7, 3.3), and HR was 1.08 (95% CI: 0.97, 1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding with a RD was 0.3 percentage point (95% CI: -3.0, 3.7), and HR was 1.09 (95% CI: 0.96, 1.25).ConclusionsInSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a severe systemic virus infectious disease usually having multi-organ dysfunction which resembles sepsis. Methods Data of 321 patients with laboratory-confirmed SFTS from May 2013 to July 2017 were retrospectively analyzed. Demographic and clinical characteristics, calculated quick sequential organ failure assessment (qSOFA) score and systemic inflammatory response syndrome (SIRS) criteria for survivors and nonsurvivors were compared. Independent risk factors associated with in-hospital mortality were obtained using multivariable logistic regression analysis. Risk score models containing different risk factors for mortality in stratified patients were established whose predictive values were evaluated using the area under ROC curve (AUC). Results Of 321 patients, 87 died (27.1%). Age (p 

Abstract Background Tuberculosis is a serious health risk, for people living with human immune deficiency virus worldwide, and the burden of TB/HIV infection is still high in Ethiopia in particular. Therefore, the aim of this study was to determine the predictors of tuberculosis infection among adults visiting anti-retroviral treatment center in East and West Gojjam, northwest, Ethiopia. Methods Institution based unmatched case-control study was employed to determine the predictors of tuberculosis infection among adults visiting anti-retroviral treatment center in east and west Gojjam, Northwest, Ethiopia from March 7–April 15, 2017. Just about 552 participants were participated in the study (139 Cases and 413 controls). Cases were confirmed with active TB and infected with HIV, and controls were HIV positive adults with non-TB. All cases in each health facility who confirmed by acid-fast bacilli, culture and gene expert were considered as TB positive. However, controls were selected by using simple random sampling technique through the above diagnostic criteria and the data were collected with Face to face interview as well as patient medical record were utilized, and the quality of the data were assured, checked, coded, cleaned and entered in EPI-Data version 3.1 and exported to SPSS version 20 for the analysis. Result Of the total sample (556), just about 552(99.2%) were participated in the study. 47.5% were females and 58.9% were rural dweller. Behavioral and modifiable biological risk factors: alcohol users (AOR = 2.33; 95%CI:1.34,4.07), BMI 

Abstract Background Group A Rotavirus (RVA), despite being an important pathogen in hospitalized children, is less studied in pediatric outpatients, and even rarely investigated in adults. This study aims to understand the genetic diversity of RVA in outpatients across all age groups in Shanghai, and thus providing a molecular basis for vaccine implementation and evaluation. Methods Stool samples were first screened by Real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR). RVA genotyping was performed through the amplification of partial VP7 and VP4 gene. Strains of interest were further sequenced and analyzed using MEGA 6.0. Results Four thousand nine hundred one samples were collected, from which 7.61% (373 cases) were screened positive for RVA. RVA prevalence was higher in children (9.30%) than in adults (7.21%) (χ2 = 4.72, P 

Abstract Background Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors and overall mortality for MDR/XDR Acinetobacter baumannii infected pediatric patients. Methods This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Acinetobacter baumannii clinical isolates were recovered from different specimens including blood, sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, ascites, hydrothorax, and urine. Antibiotic susceptibility test was determined according to the Clinical and Laboratory Standards Institute interpretive criteria. Clinical and biological data were obtained from the patients’ medical records. Results 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 male in the case group. The overall mortality rate was 29.4%, while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2% ± 3.61% vs. 9.15% ± 6.21%, P = 0.029), higher CD4+ T cell ratio (39.67% ± 12.18% vs. 32.66% ± 11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/mL vs. 0.1 (0.1, 22.99)pg/mL, P = 0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890–0.981; P = 0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425–870.574; p = 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients. Conclusion MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality. Bloodstream and central nervous system infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality.…

Abstract Background Implementation of an effective Tuberculosis Routine Surveillance System in low-income countries like Tanzania is problematic, despite being an essential tool for the detection and effective monitoring of drug resistant tuberculosis. Long delays in specimen transportation from the facilities to reference laboratory and results dissemination back to the health facilities, result in poor patient management, particularly where multidrug-resistant tuberculosis disease is present. Methods Following a detailed qualitative study, a pilot intervention of a revised Tuberculosis Routine Surveillance System was implemented in Mwanza region, Tanzania. This included the use of rapid molecular methods for the detection of both tuberculosis and drug resistance using Xpert MTB/RIF in some Mwanza sites, the use of Xpert MTB/RIF and Line Probe Assay at the Central Tuberculosis Reference Laboratory, a revised communication strategy and interventions to address the issue of poor form completion. A before and after comparison of the intervention on the number of drug resistant tuberculosis cases identified and the time taken for results feedback to the requesting site was reported. Results The revised system for previously treated cases tested at the Central Reference Laboratory was able to obtain the following findings; the number of cases tested increased from 75 in 2016 to 185 in 2017. The times for specimen transportation from health facilities to the reference laboratory were reduced by 22% (from 9 to 7 days). The median time for the district to receive results was reduced by 36% (from 11 to 7 days). Overall the number of drug resistant tuberculosis cases starting treatment increased by 67% (from 12 to 20). Conclusion Detection of drug resistance could significantly be enhanced, and delays reduced by introduction of new technologies and improved routine surveillance system, including better communication using mobile applications such as ‘WhatsApp’ and close follow-ups. A larger scale study is now merited to ascertain if these benefits are robust across different contexts.…

Background: Amphotericin B deoxycholate (AMB) has substantial toxicities. A novel encochleated amphotericin (cAMB) formulation has oral bioavailability, animal model efficacy, and minimal toxicity due to targeted drug delivery into macrophages where intracellular fungi reside.Methods: We conducted a phase I, ascending dose trial of cAMB administered at 1.0g, 1.5g, or 2.0g per day in 4-6 divided doses among HIV-positive survivors of cryptococcosis (n=9 per cohort). We assessed tolerability and adverse events (AE) over 3 days. A second trial (n=9) assessed tolerability of 1.5g/day given for 7 days.Results. In the single ascending dose study, all subjects received their full daily dose without vomiting (100% tolerability). The 1.0g cohort had 4 transient clinical AEs in 2 subjects within 48 hours, and 8 laboratory AEs (n=6 Grade 2; n=2 Grade 1). The 1.5g cohort had 7 clinical AEs in 1 subject attributed to acute gastroenteritis (n=4 Grade 2), and 5 laboratory AEs (n=1 Grade 2). The 2.0g cohort had 20 clinical AEs among 5 subjects within 48 hours (n=3 Grade 2), and 11 laboratory AEs (n=2 Grade 2, n=1 Grade 3). From a qualitative survey, 26 of 27 subjects (96%) preferred oral cAMB versus prior IV AMB experience. The second, multiple-dose cohort received 1.5g/day for one week with 98.4% (248/252) doses taken. Overall, 5 clinical AEs (n=5 Grade 1) and 6 laboratory AEs (n=6 Grade 1) occurred without kidney toxicity.Conclusions. Oral cAMB was well tolerated when given in 4-6 divided daily doses without the toxicities commonly seen with IV AMB.…

COVID-19 represents a global crisis, yet major knowledge gaps remain about human immunity to SARS-CoV-2. We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta. In PBMCs of COVID-19 patients, there was reduced expression of HLA-DR and pro-inflammatory cytokines by myeloid cells, and impaired mTOR-signaling and IFN-α production by plasmacytoid DCs. In contrast, there were enhanced plasma levels of inflammatory mediators, including EN-RAGE, TNFSF14, and oncostatin-M, which correlated with disease severity and increased bacterial products in human plasma. Single-cell transcriptomics revealed no type-I IFN, reduced HLA-DR in myeloid cells of severe patients, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics, and transient, low plasma IFN-α levels during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.…

Eskild Petersen and colleagues published a relevant comparison of the novel coronavirus outbreak with past influenza pandemics.1 Here we comment on fatality rates, considering evidence for the pathogenesis of these two respiratory viruses.

The Personal View by Euzebiusz Jamrozik and Michael Selgelid1 was helpful in laying out some of the key ethical issues with human challenge trials for COVID-19. This response provides both an alternative perspective and an updated viewpoint about the ethical tradeoffs involved. In short, because of the urgency of the situation, the landscape has evolved significantly, even in the past month, and many experts feel the ethical concerns voiced can now be addressed.2…

On Dec 31, 2019, the Wuhan Municipal Health Commission (Wuhan, China), reported a cluster of cases of pneumonia to WHO. A novel coronavirus was identified—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—and the outbreak was declared as a Public Health Emergency of International Concern in January, 2020. The virus subsequently spread rapidly throughout China and other countries worldwide, and on March 11, 2020, the outbreak was declared a pandemic. Since March 11, 2020, the virus has continued to spread, causing substantial morbidity and mortality in many countries.

Although rare in the US, antibiotic-resistant strains of Neisseria meningitidis have been detected in a dozen states, according to a CDC report.

An over-the-counter supplement promising male sexual enhancement led at least 17 men in Virginia to develop severe hypoglycemia in 2019, the CDC reported.

Relieved that the spot appearing on the x-ray of your back after your fall turns out to be not in your lungs as feared but in your stomach and theoretically a Tums, I jog your memory of the x-ray vans that visited our high school in 1966, how the big fat lot of us filed through so they could look into our clandestine chests. We wonder if the techs enjoyed the shadows of animals and curse words cut from foil some placed beneath their shirts, though in your first love they found a tumor. You say the two of you had sex in his hospital room, that he told you to look out the window, surprising you from behind. Then we laugh, fools that we are, at my threatened eyesight and your thwarted chemo. Mortality at bay, we’re young again.

This randomized trial compares the effects of higher add power (+2.50 D) vs lower add power (+1.50 D) soft multifocal contact lenses vs single-vision contact lenses on myopia progression at 3 years in children aged 7 to 11 years with myopia.

This randomized clinical trial assesses the effect of liberal vs restrictive red blood cell transfusion thresholds (based on postnatal age and current health state) on death or disability at 24 months of age among extremely low-birth-weight infants.

In Reply We agree with Drs Mehta and Blackhall that a POLST may not always accurately reflect a patient’s goals of care at the time of completion for a number of reasons, and that this inaccuracy is one potential cause of POLST-discordant intensive care. The fact that patients and surrogates do not always recall or even agree with their own POLSTs strongly suggests that there is room for improvement in the initial completion of POLSTs. Additionally, there are emerging data that mapping patients’ values (eg, prioritization of comfort over longevity) to discrete treatment preferences (eg, no cardiopulmonary resuscitation or intensive care) is a complicated and perhaps error-prone process for many patients. We also agree that the process of completing a POLST form should be closely guided by clinicians and that there is a need for more education of clinicians so that they can help patients and surrogates complete POLSTs that both accurately reflect goals and can be implemented during acute illness. However, effective implementation of POLSTs may require more than simple educational interventions. The enormous variability in the reported efficacies of advance care planning interventions suggests that effective interventions may have key features for success that are often not replicated with fidelity in clinical practice. Such differences in implementation may arise because of limitations in resources, time, and effective point-of-care tools.

In Reply A total of 14 studies (8 randomized trials and 6 observational studies) have already evaluated the effects of high-dose vitamin C, thiamine, and steroids in more than 2000 patients with sepsis in 10 different countries, and the overall results have been disappointing. In addition, 12 other trials are now completed according to ClinicalTrials.gov. Thus, a large amount of new information on this combination treatment will soon be reported.

To the Editor Dr Lee and colleagues found that 38% of patients with treatment-limiting Physician Orders for Life-Sustaining Treatment (POLST) received intensive care that was discordant with the POLST. In their Editorial, Drs Truog and Fried suggested reasons for this discordance, including differing health status between time of POLST completion and implementation, and the inability of the form to reflect changes in preferences. We offer a third explanation that may account for the discordant care found in the study: that the POLST form may not be completed correctly at the time of recording.

To the Editor Since a single-center, 94-patient, uncontrolled observational study of the combination therapy of vitamin C, thiamine, and hydrocortisone reported a 32% absolute mortality reduction in patients with sepsis in 2017, several investigators have tested vitamin C and combination therapy in clinical trials. The recently published Vitamin C, Hydrocortisone and Thiamine in Patients With Septic Shock (VITAMINS) trial reported no difference in the primary outcome of time alive and free of vasopressors. We agree that the results of the VITAMINS trial should temper enthusiasm for the use of vitamin C therapy outside of clinical trials, which some had adopted after the 2017 report.

This pharmacoepidemiology study uses NHANES data to characterize the prevalence and trends in use of high-dosage biotin supplementation among US adults between 1999 and 2016.

In the modern history of the biologic sciences and particularly in medicine, antiseptics and germicides have played such unanticipated parts and have been responsible for so much which is good that they have furnished words to conjure with. Every force that can be enlisted against baneful bacteria is promptly welcomed; but there are no “royal roads” to success in the warfare against these invisible foes, just as there are no panaceas with which every human ailment can be relieved. Surgeons of the present day have seen the pendulum of operative practice swing between antisepsis and asepsis without discovering the ultimate ideal of a universally applicable scheme of procedure. Only a few years ago, physicians were greatly exercised by the hope of finding a satisfactory intestinal antiseptic. Naturally the possibility of being able to rid the alimentary tract of its undesirable microbiotic invaders aroused widespread interest. Despite the numerous efforts to demonstrate the efficacy of this or that chemical agent or drug as a gastro-intestinal antiseptic, the outcome has been that the supposed benefits were due to catharsis in most instances rather than to any real effect upon the bacteria in situ. The emptying of the bowel is, in truth, probably the most successful mode of decreasing its bacterial flora, according to present-day knowledge.

In 2018, national health care spending increased by 4.6%, reaching $11 000 per person. Amid this growth, states are seeking novel ways to protect their budgets. One approach is to set a cost growth benchmark—a percentage growth rate under which states aim to maintain annual health care costs.