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1.
Pan Afr Med J ; 38: 74, 2021.
Article in English | MEDLINE | ID: covidwho-1547719

ABSTRACT

Boerhaave's syndrome is an uncommon syndrome characterized by spontaneous rupture of the oesophagus with a high mortality rate. While excessive alcohol intake and binge-eating are the classic precipitants of this syndrome, medication-induced vomiting causing Booerhave's is quite uncommon. Traditionally managed operatively, conservative management is being increasingly reported in selected cases. We report the case of 21-year-old male with who developed sudden onset chest pain and dyspnoea after pentazocine induced vomiting. He was referred after lack of response to initial treatment for acute severe asthma. A chest CT scan showed pneumomediastinum, subcutaneous emphysema and oesophageal tear. He was managed conservatively with oxygen therapy, nil per mouth and antibiotics with improvement of symptoms and discharge after 8 days.


Subject(s)
Esophageal Perforation/diagnostic imaging , Mediastinal Diseases/diagnostic imaging , Pentazocine/adverse effects , Vomiting/complications , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Anti-Bacterial Agents/administration & dosage , Asthma/physiopathology , Asthma/therapy , Chest Pain/etiology , Dyspnea/etiology , Esophageal Perforation/etiology , Esophageal Perforation/therapy , Humans , Male , Mediastinal Diseases/etiology , Mediastinal Diseases/therapy , Oxygen Inhalation Therapy , Pentazocine/administration & dosage , Tomography, X-Ray Computed , Vomiting/chemically induced , Young Adult
2.
Lancet Infect Dis ; 21(5): 657-667, 2021 05.
Article in English | MEDLINE | ID: covidwho-1510463

ABSTRACT

BACKGROUND: Bacterial sexually transmitted infections (STIs) are highly prevalent among men who have sex with men who use HIV pre-exposure prophylaxis (PrEP), which leads to antimicrobial consumption linked to the emergence of antimicrobial resistance. We aimed to assess use of an antiseptic mouthwash as an antibiotic sparing approach to prevent STIs. METHODS: We invited people using PrEP who had an STI in the past 24 months to participate in this single-centre, randomised, double-blind, placebo-controlled, AB/BA crossover superiority trial at the Institute of Tropical Medicine in Antwerp, Belgium. Using block randomisation (block size eight), participants were assigned (1:1) to first receive Listerine Cool Mint or a placebo mouthwash. They were required to use the study mouthwashes daily and before and after sex for 3 months each and to ask their sexual partners to use the mouthwash before and after sex. Participants were screened every 3 months for syphilis, chlamydia, and gonorrhoea at the oropharynx, anorectum, and urethra. The primary outcome was combined incidence of these STIs during each 3-month period, assessed in the intention-to-treat population, which included all participants who completed at least the first 3-month period. Safety was assessed as a secondary outcome. This trial is registered with Clinicaltrials.gov, NCT03881007. FINDINGS: Between April 2, 2019, and March 13, 2020, 343 participants were enrolled: 172 in the Listerine followed by placebo (Listerine-placebo) group and 171 in the placebo followed by Listerine (placebo-Listerine) group. The trial was terminated prematurely because of the COVID-19 pandemic. 151 participants completed the entire study, and 89 completed only the first 3-month period. 31 participants withdrew consent, ten were lost to follow-up, and one acquired HIV. In the Listerine-placebo group, the STI incidence rate was 140·4 per 100 person-years during the Listerine period, and 102·6 per 100 person-years during the placebo period. In the placebo-Listerine arm, the STI incidence rate was 133·9 per 100 person-years during the placebo period, and 147·5 per 100 person-years during the Listerine period. We did not find that Listerine significantly reduced STI incidence (IRR 1·17, 95% CI 0·84-1·64). Numbers of adverse events were not significantly higher than at baseline and were similar while using Listerine and placebo. Four serious adverse events (one HIV-infection, one severe depression, one Ludwig's angina, and one testicular carcinoma) were not considered to be related to use of mouthwash. INTERPRETATION: Our findings do not support the use of Listerine Cool Mint as a way to prevent STI acquisition among high-risk populations. FUNDING: Belgian Research Foundation - Flanders (FWO 121·00).


Subject(s)
Anti-Bacterial Agents/administration & dosage , HIV Infections/prevention & control , Homosexuality, Male , Mouthwashes , Pre-Exposure Prophylaxis , Sexually Transmitted Diseases/prevention & control , Adult , Cross-Over Studies , Double-Blind Method , Humans , Incidence , Male , Middle Aged , Sexually Transmitted Diseases/epidemiology
3.
Ther Drug Monit ; 43(4): 451-454, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1501177

ABSTRACT

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefepime/pharmacokinetics , Critical Illness/therapy , Drug Dosage Calculations , Precision Medicine/methods , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Cefepime/administration & dosage , Cefepime/adverse effects , Humans , Male , Middle Aged
4.
Ann Med ; 53(1): 1863-1874, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1483235

ABSTRACT

OBJECTIVE: To compare the performance of the Risk-stratification of Emergency Department suspected Sepsis (REDS) score to the SIRS criteria, NEWS2, CURB65, SOFA, MEDS and PIRO scores, to risk-stratify Emergency Department (ED) suspected sepsis patients for mortality. METHOD: A retrospective observational cohort study of prospectively collected data. Adult patients admitted from the ED after receiving intravenous antibiotics for suspected sepsis in the year 2020, were studied. Patients with COVID-19 were excluded. The scores stated above were calculated for each patient. Receiver operator characteristics (ROC) curves were constructed for each score for the primary outcome measure, all-cause in-hospital mortality. The area under the ROC (AUROC) curves and cut-off points were identified by the statistical software. Scores above the cut-off point were deemed high-risk. The test characteristics of the high-risk groups were calculated. Comparisons were based on the AUROC curve and sensitivity for mortality of the high-risk groups. Previously published cut-off points were also studied. Calibration was also studied. RESULTS: Of the 2594 patients studied, 332 (12.8%) died. The AUROC curve for the REDS score 0.73 (95% confidence interval [CI] 0.72-0.75) was significantly greater than the AUROC curve for the SIRS criteria 0.51 (95% CI 0.49-0.53), p < .0001 and the NEWS2 score 0.69 (95% CI 0.67-0.70), p = .005, and similar to all other scores studied. Sensitivity for mortality at the respective cut-off points identified (REDS ≥3, NEWS2 ≥ 8, CURB65 ≥ 3, SOFA ≥3, MEDS ≥10 and PIRO ≥10) was greatest for the REDS score at 80.1% (95% CI 75.4-84.3) and significantly greater than the other scores. The sensitivity for mortality for an increase of two points from baseline in the SOFA score was 63% (95% CI 57.5-68.2). CONCLUSIONS: In this single centre study, the REDS score had either a greater AUROC curve or sensitivity for mortality compared to the comparator scores, at the respective cut-off points identified.KEY MESSAGESThe REDS score is a simple and objective scoring system to risk-stratify for mortality in emergency department (MED) patients with suspected sepsis.The REDS score is better or equivalent to existing scoring systems in its discrimination for mortality.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Emergency Service, Hospital/statistics & numerical data , Intensive Care Units/statistics & numerical data , Sepsis/mortality , Severity of Illness Index , Administration, Intravenous , Aged , Aged, 80 and over , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Prospective Studies , ROC Curve , Retrospective Studies , Risk Assessment/methods , Sepsis/diagnosis , Sepsis/drug therapy
5.
J Laryngol Otol ; 135(10): 855-857, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1434031

ABSTRACT

OBJECTIVE: Recurrent acute otitis media is common in children. The preferred treatment measures for recurrent acute otitis media have a mixed evidence base. This study sought to assess baseline practice across ENT departments in England. METHODS: A national telephone survey of healthcare staff was conducted. Every ENT centre in England was contacted. A telephone script was used to ask about antibiotic and grommet use and duration in recurrent acute otitis media cases. RESULTS: Ninety-six centres (74 per cent) provided complete information. Recurrent acute otitis media treatment across England by ENT departments varied. The antibiotic first- and second-line prophylaxis offered varies, with trimethoprim used in 33 centres and 29 centres not offering any antibiotics. The timing or choice about when to use grommets also varies, but 87 centres (91 per cent) offer grommet surgery at one stage. CONCLUSION: The treatments received by children in England for recurrent acute otitis media vary by centre; collaborative research in this area is advised.


Subject(s)
Middle Ear Ventilation/statistics & numerical data , Otitis Media/drug therapy , Otolaryngology/statistics & numerical data , Surveys and Questionnaires/standards , Acute Disease , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents, Urinary/administration & dosage , Anti-Infective Agents, Urinary/therapeutic use , Child , Drug Resistance, Microbial , England/epidemiology , Humans , Middle Ear Ventilation/methods , Otitis Media/surgery , Otolaryngology/organization & administration , Personal Health Services/statistics & numerical data , Recurrence , State Medicine/organization & administration , Surveys and Questionnaires/statistics & numerical data , Trimethoprim/administration & dosage , Trimethoprim/therapeutic use
9.
JAMA ; 326(6): 490-498, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1363618

ABSTRACT

Importance: Azithromycin has been hypothesized to have activity against SARS-CoV-2. Objective: To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14. Design, Setting, and Participants: Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization. Interventions: Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92). Main Outcomes and Measures: The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21. Results: Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16). Conclusions and Relevance: Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection. Trial Registration: ClinicalTrials.gov Identifier: NCT04332107.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , SARS-CoV-2 , Administration, Oral , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19/complications , Female , Humans , Male , Middle Aged , Outpatients , Symptom Assessment , Treatment Failure
10.
Lancet Respir Med ; 9(9): 1010-1020, 2021 09.
Article in English | MEDLINE | ID: covidwho-1331331

ABSTRACT

BACKGROUND: Doxycycline is often used for treating COVID-19 respiratory symptoms in the community despite an absence of evidence from clinical trials to support its use. We aimed to assess the efficacy of doxycycline to treat suspected COVID-19 in the community among people at high risk of adverse outcomes. METHODS: We did a national, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in older people (PRINCIPLE) across primary care centres in the UK. We included people aged 65 years or older, or 50 years or older with comorbidities (weakened immune system, heart disease, hypertension, asthma or lung disease, diabetes, mild hepatic impairment, stroke or neurological problem, and self-reported obesity or body-mass index of 35 kg/m2 or greater), who had been unwell (for ≤14 days) with suspected COVID-19 or a positive PCR test for SARS-CoV-2 infection in the community. Participants were randomly assigned using response adaptive randomisation to usual care only, usual care plus oral doxycycline (200 mg on day 1, then 100 mg once daily for the following 6 days), or usual care plus other interventions. The interventions reported in this manuscript are usual care plus doxycycline and usual care only; evaluations of other interventions in this platform trial are ongoing. The coprimary endpoints were time to first self-reported recovery, and hospitalisation or death related to COVID-19, both measured over 28 days from randomisation and analysed by intention to treat. This trial is ongoing and is registered with ISRCTN, 86534580. FINDINGS: The trial opened on April 2, 2020. Randomisation to doxycycline began on July 24, 2020, and was stopped on Dec 14, 2020, because the prespecified futility criterion was met; 2689 participants were enrolled and randomised between these dates. Of these, 2508 (93·3%) participants contributed follow-up data and were included in the primary analysis: 780 (31·1%) in the usual care plus doxycycline group, 948 in the usual care only group (37·8%), and 780 (31·1%) in the usual care plus other interventions group. Among the 1792 participants randomly assigned to the usual care plus doxycycline and usual care only groups, the mean age was 61·1 years (SD 7·9); 999 (55·7%) participants were female and 790 (44·1%) were male. In the primary analysis model, there was little evidence of difference in median time to first self-reported recovery between the usual care plus doxycycline group and the usual care only group (9·6 [95% Bayesian Credible Interval [BCI] 8·3 to 11·0] days vs 10·1 [8·7 to 11·7] days, hazard ratio 1·04 [95% BCI 0·93 to 1·17]). The estimated benefit in median time to first self-reported recovery was 0·5 days [95% BCI -0·99 to 2·04] and the probability of a clinically meaningful benefit (defined as ≥1·5 days) was 0·10. Hospitalisation or death related to COVID-19 occurred in 41 (crude percentage 5·3%) participants in the usual care plus doxycycline group and 43 (4·5%) in the usual care only group (estimated absolute percentage difference -0·5% [95% BCI -2·6 to 1·4]); there were five deaths (0·6%) in the usual care plus doxycycline group and two (0·2%) in the usual care only group. INTERPRETATION: In patients with suspected COVID-19 in the community in the UK, who were at high risk of adverse outcomes, treatment with doxycycline was not associated with clinically meaningful reductions in time to recovery or hospital admissions or deaths related to COVID-19, and should not be used as a routine treatment for COVID-19. FUNDING: UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research.


Subject(s)
Anti-Bacterial Agents/administration & dosage , COVID-19/drug therapy , Doxycycline/administration & dosage , Age Factors , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Doxycycline/adverse effects , Female , Hospitalization/statistics & numerical data , Humans , Intention to Treat Analysis , Male , Middle Aged , Minimal Clinically Important Difference , Risk Factors , SARS-CoV-2/isolation & purification , Self Report/statistics & numerical data , Treatment Outcome , United Kingdom/epidemiology
11.
Cornea ; 40(11): 1502-1504, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1328949

ABSTRACT

ABSTRACT: The coronavirus disease 2019 global pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several ophthalmic manifestations have been reported to be associated with SARS-CoV-2 infection, including conjunctivitis, acute sixth nerve palsy, and multiple cranial neuropathies. We present a unique case of unilateral phlyctenular keratoconjunctivitis in a 5-year-old boy in the setting of SARS-CoV-2 infection.


Subject(s)
COVID-19/diagnosis , Conjunctivitis, Viral/diagnosis , Eye Infections, Viral/diagnosis , Keratoconjunctivitis/diagnosis , SARS-CoV-2/pathogenicity , Administration, Oral , Anti-Bacterial Agents/administration & dosage , Ascorbic Acid/administration & dosage , Azithromycin/administration & dosage , COVID-19/drug therapy , COVID-19/virology , COVID-19 Nucleic Acid Testing , Child, Preschool , Conjunctivitis, Viral/drug therapy , Conjunctivitis, Viral/virology , Drug Therapy, Combination , Eye Infections, Viral/drug therapy , Eye Infections, Viral/virology , Fluorometholone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Keratoconjunctivitis/drug therapy , Keratoconjunctivitis/virology , Male , Ophthalmic Solutions , Slit Lamp Microscopy , Tomography, Optical Coherence , Visual Acuity/physiology
13.
Am J Health Syst Pharm ; 77(17): 1409-1416, 2020 08 20.
Article in English | MEDLINE | ID: covidwho-1317900

ABSTRACT

PURPOSE: The global coronavirus disease 2019 (COVID-19) pandemic has created unprecedented strains on healthcare systems around the world. Challenges surrounding an overwhelming influx of patients with COVID-19 and changes in care dynamics prompt the need for care models and processes that optimize care in this medically complex patient population. The purpose of this report is to describe our institution's strategy to deploy pharmacy resources and standardize pharmacy processes to optimize the management of patients with COVID-19. METHODS: This retrospective, descriptive report characterizes documented pharmacy interventions in the acute care of patients admitted for COVID-19 during the period April 1 to April 15, 2020. Patient monitoring, interprofessional communication, and intervention documentation by pharmacy staff was facilitated through the development of a COVID-19-specific care bundle integrated into the electronic medical record. RESULTS: A total of 1,572 pharmacist interventions were documented in 197 patients who received a total of 15,818 medication days of therapy during the study period. The average number of interventions per patient was 8. The most common interventions were regimen simplification (15.9%), timing and dosing adjustments (15.4%), and antimicrobial therapy and COVID-19 treatment adjustments (15.2%). Patients who were admitted to an intensive care unit care at any point during their hospital stay accounted for 66.7% of all interventions documented. CONCLUSION: A pharmacy department's response to the COVID-19 pandemic was optimized through standardized processes. Pharmacists intervened to address a wide scope of medication-related issues, likely contributing to improved management of COVID-19 patients. Results of our analysis demonstrate the vital role pharmacists play as members of multidisciplinary teams during times of crisis.


Subject(s)
COVID-19/drug therapy , Medication Therapy Management/organization & administration , Pharmacists/organization & administration , Pharmacy Service, Hospital/organization & administration , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/epidemiology , Critical Care/organization & administration , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Electrolytes/administration & dosage , Electrolytes/adverse effects , Female , Hospital Mortality , Humans , Intensive Care Units/organization & administration , Interdisciplinary Communication , Male , Medical Records Systems, Computerized/organization & administration , Middle Aged , Pandemics/prevention & control , Professional Role , Retrospective Studies , Treatment Outcome
14.
JAMA ; 326(6): 490-498, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1315243

ABSTRACT

Importance: Azithromycin has been hypothesized to have activity against SARS-CoV-2. Objective: To determine whether oral azithromycin in outpatients with SARS-CoV-2 infection leads to absence of self-reported COVID-19 symptoms at day 14. Design, Setting, and Participants: Randomized clinical trial of azithromycin vs matching placebo conducted from May 2020 through March 2021. Outpatients from the US were enrolled remotely via internet-based surveys and followed up for 21 days. Eligible participants had a positive SARS-CoV-2 diagnostic test result (nucleic acid amplification or antigen) within 7 days prior to enrollment, were aged 18 years or older, and were not hospitalized at the time of enrollment. Among 604 individuals screened, 297 were ineligible, 44 refused participation, and 263 were enrolled. Participants, investigators, and study staff were masked to treatment randomization. Interventions: Participants were randomized in a 2:1 fashion to a single oral 1.2-g dose of azithromycin (n = 171) or matching placebo (n = 92). Main Outcomes and Measures: The primary outcome was absence of self-reported COVID-19 symptoms at day 14. There were 23 secondary clinical end points, including all-cause hospitalization at day 21. Results: Among 263 participants who were randomized (median age, 43 years; 174 [66%] women; 57% non-Hispanic White and 29% Latinx/Hispanic), 76% completed the trial. The trial was terminated by the data and safety monitoring committee for futility after the interim analysis. At day 14, there was no significant difference in proportion of participants who were symptom free (azithromycin: 50%; placebo: 50%; prevalence difference, 0%; 95% CI, -14% to 15%; P > .99). Of 23 prespecified secondary clinical end points, 18 showed no significant difference. By day 21, 5 participants in the azithromycin group had been hospitalized compared with 0 in the placebo group (prevalence difference, 4%; 95% CI, -1% to 9%; P = .16). Conclusions and Relevance: Among outpatients with SARS-CoV-2 infection, treatment with a single dose of azithromycin compared with placebo did not result in greater likelihood of being symptom free at day 14. These findings do not support the routine use of azithromycin for outpatient SARS-CoV-2 infection. Trial Registration: ClinicalTrials.gov Identifier: NCT04332107.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , SARS-CoV-2 , Administration, Oral , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19/complications , Female , Humans , Male , Middle Aged , Outpatients , Symptom Assessment , Treatment Failure
17.
Nature ; 594(7862): 234-239, 2021 06.
Article in English | MEDLINE | ID: covidwho-1269388

ABSTRACT

Loss of gut microbial diversity1-6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.


Subject(s)
Bacteria/isolation & purification , Biodiversity , Biological Evolution , Feces/microbiology , Gastrointestinal Microbiome , Genome, Bacterial/genetics , Host Microbial Interactions , Anti-Bacterial Agents/administration & dosage , Bacteria/classification , Bacteria/genetics , Chronic Disease , Developed Countries , Developing Countries , Diet, Western , History, Ancient , Humans , Industrial Development/trends , Methanobrevibacter/classification , Methanobrevibacter/genetics , Methanobrevibacter/isolation & purification , Mexico , Sedentary Behavior , Southwestern United States , Species Specificity , Symbiosis
18.
Nat Commun ; 12(1): 3554, 2021 06 11.
Article in English | MEDLINE | ID: covidwho-1265949

ABSTRACT

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies.


Subject(s)
COVID-19/immunology , Adult , Africa South of the Sahara/epidemiology , Anti-Bacterial Agents/administration & dosage , Antibodies/blood , COVID-19/blood , COVID-19/drug therapy , COVID-19/epidemiology , Coinfection/immunology , Cytokines/blood , Dexamethasone/administration & dosage , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics , SARS-CoV-2/isolation & purification
19.
PLoS One ; 16(5): e0251340, 2021.
Article in English | MEDLINE | ID: covidwho-1223800

ABSTRACT

BACKGROUND: Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. METHODS: The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. RESULTS: Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). CONCLUSION: The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful.


Subject(s)
Anti-Bacterial Agents/adverse effects , COVID-19/pathology , Inappropriate Prescribing/adverse effects , Acute Kidney Injury/etiology , Aged , Anti-Bacterial Agents/administration & dosage , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/virology , Comorbidity , Cough/etiology , Dyspnea/etiology , Female , Fever/etiology , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Registries , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
20.
Ther Drug Monit ; 43(4): 451-454, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1197045

ABSTRACT

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefepime/pharmacokinetics , Critical Illness/therapy , Drug Dosage Calculations , Precision Medicine/methods , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Cefepime/administration & dosage , Cefepime/adverse effects , Humans , Male , Middle Aged
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