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1.
Cardiol Rev ; 29(6): 289-291, 2021.
Article in English | MEDLINE | ID: covidwho-20244180

ABSTRACT

The ongoing coronavirus infection-2019 (COVID-19) global pandemic has had devastating impacts on the global population since 2019. Cardiac complications are a well-documented sequala of COVID-19, with exposed patients experiencing complications such as myocardial infarction, myocarditis, and arrythmias. This article aims to review prominent literature regarding COVID-19 and its link with arrhythmias, as well as to discuss some of the possible mechanisms by which arrhythmogenesis may occur in patients with COVID-19.


Subject(s)
Arrhythmias, Cardiac/epidemiology , COVID-19/epidemiology , Anti-Bacterial Agents/adverse effects , Antirheumatic Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/physiopathology , Azithromycin/adverse effects , COVID-19/physiopathology , Humans , Hydroxychloroquine/adverse effects , Intensive Care Units , SARS-CoV-2 , Severity of Illness Index , COVID-19 Drug Treatment
2.
Indian J Ophthalmol ; 71(5): 2275-2279, 2023 05.
Article in English | MEDLINE | ID: covidwho-2324969

ABSTRACT

A woman reported decreased vision in the right eye since hospitalization for COVID-19. Vision in the right eye was 6/18 and in the left eye was counting fingers. Her left eye had cataract and right eye was pseudophakic with earlier documented good recovery. In the right eye, she had branch retinal vein occlusion (BRVO) with macular edema documented on optical coherence tomography (OCT). It was suspected that it might be an ocular manifestation of COVID-19 which had not been reported and had worsened. An overdose of antibiotics or remdesivir might also be responsible for the same. She was advised anti-VEGF injections and was kept under treatment.


Subject(s)
COVID-19 , Retinal Vein Occlusion , Humans , Female , Anticoagulants/therapeutic use , Anti-Bacterial Agents/adverse effects , COVID-19 Drug Treatment , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Vitreous Body , Tomography, Optical Coherence , Intravitreal Injections
3.
BMC Nephrol ; 24(1): 140, 2023 05 22.
Article in English | MEDLINE | ID: covidwho-2322526

ABSTRACT

BACKGROUND: Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19. METHODOLOGY: A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission. RESULTS: A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73-2.99), age (OR 1.02, 95% CI 1.01-1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03-6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10-20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14-1.71), the use of vancomycin (OR 1.57, 95% CI 1.05-2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2-2.31), and vasopressor support (CI 2.39, 95% CI 1.53-3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI. CONCLUSIONS: This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19.


Subject(s)
Acute Kidney Injury , COVID-19 , Hypertension , Renal Insufficiency, Chronic , Adult , Humans , Male , Female , Anti-Bacterial Agents/adverse effects , Retrospective Studies , COVID-19/epidemiology , COVID-19/complications , Risk Factors , Hypertension/complications , Acute Kidney Injury/etiology , Renal Insufficiency, Chronic/complications , Hospital Mortality
4.
Eur Respir Rev ; 31(166)2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2300932

ABSTRACT

Severe community-acquired pneumonia is the most life-threatening form of community-acquired pneumonia, characterised by intensive care unit admission and high morbidity and mortality. In this review article, we cover in depth six aspects of severe community-acquired pneumonia that are still controversial: use of PCR molecular techniques for microbial diagnosis; the role of biomarkers for initial management; duration of treatment, macrolides or quinolones in the initial empirical antibiotic therapy; the use of prediction scores for drug-resistant pathogens to modify initial empiric therapy; the use of noninvasive mechanical ventilation and high-flow nasal oxygen; and the use of corticosteroids as adjunctive therapy in severe community-acquired pneumonia.


Subject(s)
Community-Acquired Infections , Pneumonia , Humans , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Pneumonia/diagnosis , Pneumonia/drug therapy , Macrolides/adverse effects , Anti-Bacterial Agents/adverse effects , Intensive Care Units
5.
Arch Dis Child ; 108(3): 192-197, 2023 03.
Article in English | MEDLINE | ID: covidwho-2264240

ABSTRACT

OBJECTIVE: To evaluate a new protocol of risk stratification and early discharge for children with febrile neutropenia (FN). DESIGN: Prospective service evaluation from 17 April 2020 to 16 April 2021. SETTING: 13 specialist centres in the UK. PATIENTS: 405 children presenting with FN. INTERVENTION: All children received intravenous antibiotics at presentation. Risk stratification was determined using the Australian-UK-Swiss (AUS) rule and eligibility for homecare assessed using criteria including disease, chemotherapy, presenting features and social factors. Those eligible for homecare could be discharged on oral antibiotics after a period of observation proportional to their risk group. MAIN OUTCOME MEASURES: Median duration of admission and of intravenous antibiotics, and percentage of patients with positive blood cultures, significant infection, readmission within 7 days of initial presentation, intensive care unit (ICU) admission, death from infection and death from other causes. RESULTS: 13 centres contributed 729 initial presentations of 405 patients. AUS rule scores were positively correlated with positive blood cultures, significant infection, ICU admission and death. 20% of children were eligible for homecare with oral antibiotics, of which 55% were low risk (AUS 0-1). 46% low-risk homecare eligible patients were discharged by 24 hours vs 2% homecare ineligible. Homecare readmission rates were 14% overall and 16% for low-risk cases (similar to a meta-analysis of previous studies). No child eligible for homecare was admitted to ICU or died. CONCLUSIONS: Use of the AUS rule and homecare criteria allow for safe early outpatient management of children with FN.


Subject(s)
Febrile Neutropenia , Neoplasms , Child , Humans , Anti-Bacterial Agents/adverse effects , Patient Discharge , Prospective Studies , Australia/epidemiology , United Kingdom , Neoplasms/drug therapy , Meta-Analysis as Topic
7.
Lancet Infect Dis ; 23(6): 673-682, 2023 06.
Article in English | MEDLINE | ID: covidwho-2211758

ABSTRACT

BACKGROUND: The COVID-19 pandemic has been associated with increased antimicrobial use despite low rates of bacterial co-infection. Prospective audit and feedback is recommended to optimise antibiotic prescribing, but high-quality evidence supporting its use for COVID-19 is absent. We aimed to study the efficacy and safety of prospective audit and feedback in patients admitted to hospital for the treatment of COVID-19. METHODS: COVASP was a prospective, pragmatic, non-inferiority, small-unit, cluster-randomised trial comparing prospective audit and feedback plus standard of care with standard of care alone in adults admitted to three hospitals in Edmonton, AB, Canada, with COVID-19 pneumonia. All patients aged at least 18 years who were admitted from the community to a designated study bed with microbiologically confirmed SARS-CoV-2 infection in the preceding 14 days were included if they had an oxygen saturation of 94% or lower on room air, required supplemental oxygen, or had chest-imaging findings compatible with COVID-19 pneumonia. Patients were excluded if they were transferred in from another acute care centre, enrolled in another clinical trial that involved antibiotic therapy, expected to progress to palliative care or death within 48 h of hospital admission, or managed by any member of the research team within 30 days of enrolment. COVID-19 unit and critical care unit beds were stratified and randomly assigned (1:1) to the prospective audit and feedback plus standard of care group or the standard of care group. Patients were masked to their bed assignment but the attending physician and study team were not. The primary outcome was clinical status on postadmission day 15, measured using a seven-point ordinal scale. We used a non-inferiority margin of 0·5. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT04896866, and is now closed. FINDINGS: Between March 1 and Oct 29, 2021, 1411 patients were screened and 886 were enrolled: 457 into the prospective audit and feedback plus standard of care group, of whom 429 completed the study, and 429 into the standard of care group, of whom 404 completed the study. Baseline characteristics were similar for both groups, with an overall mean age of 56·7 years (SD 17·3) and a median baseline ordinal scale of 4·0 (IQR 4·0-5·0). 301 audit and feedback events were recorded in the intervention group and 215 recommendations were made, of which 181 (84%) were accepted. Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364·9 vs 384·2 days per 1000 patient days), clinical status at postadmission day 15 was non-inferior (median ordinal score 2·0 [IQR 2·0-3·0] vs 2·0 [IQR 2·0-4·0]; p=0·37, Mann-Whitney U test). Neutropenia was uncommon in both the intervention group (13 [3%] of 420 patients) and the control group (20 [5%] of 396 patients), and acute kidney injury occurred at a similar rate in both groups (74 [18%] of 421 patients in the intervention group and 76 [19%] of 399 patients in the control group). No intervention-related deaths were recorded. INTERPRETATION: This cluster-randomised clinical trial shows that prospective audit and feedback is safe and effective in optimising and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population. FUNDING: None.


Subject(s)
Antimicrobial Stewardship , Bacterial Infections , COVID-19 , Adult , Humans , Adolescent , Middle Aged , SARS-CoV-2 , Feedback , Pandemics , Anti-Bacterial Agents/adverse effects , Bacterial Infections/drug therapy , Treatment Outcome
8.
Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med ; 30(s1): 1044-1049, 2022 Dec 15.
Article in Russian | MEDLINE | ID: covidwho-2117152

ABSTRACT

The review traces the evolution of the section on the use of antibacterial drugs in the temporary guidelines of the Ministry of Health for the treatment of a new coronavirus infection. Diagnostic approaches that play an important role in deciding on the need and duration of antibacterial therapy are presented. Routine use of fluoroquinolones should be restricted due to the adverse safety spectrum. According to existing data, the tactic of short courses of antibacterial therapy for community-acquired pneumonia are not inferior in effectiveness to longer courses. Unjustified prescribing of antibiotics increases the cost of medical care, promotes the selection of resistant pathogens and leads to adverse side effects. Timely updating of clinical recommendations, implementation of programs to control the appointment of antibacterial agents in medical organizations and strengthening the role of the clinical pharmacology service can reduce these adverse events.


Subject(s)
COVID-19 Drug Treatment , Community-Acquired Infections , Pneumonia , Humans , Anti-Bacterial Agents/adverse effects , Community-Acquired Infections/drug therapy
9.
Clin Drug Investig ; 42(11): 921-935, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2094844

ABSTRACT

Macrolides such as azithromycin are commonly prescribed antibiotics during pregnancy. The good oral bioavailability and transplacental transfer of azithromycin make this drug suitable for the treatment of sexually transmitted diseases, toxoplasmosis, and malaria. Moreover, azithromycin is useful both in the management of preterm pre-labor rupture of membranes and in the adjunctive prophylaxis for cesarean delivery. The aim of this comprehensive narrative review is to critically analyze and summarize the available literature on the main aspects of azithromycin use in pregnant women, with a special focus on adverse offspring outcomes associated with prenatal exposure to the drug. References for this review were identified through searches of MEDLINE, PubMed, and EMBASE. Fetal and neonatal outcomes following prenatal azithromycin exposure have been investigated in several studies, yielding conflicting results. Increased risks of spontaneous miscarriage, major congenital malformations, cardiovascular malformations, digestive system malformations, preterm birth, and low birth weight have been reported in some studies but not in others. Currently, there is no conclusive evidence to support that azithromycin use by pregnant women causes adverse outcomes in their offspring. Therefore, this agent should only be used during pregnancy when clinically indicated, if the benefits of treatment are expected to outweigh the potential risks.


Subject(s)
Azithromycin , Premature Birth , Infant, Newborn , Pregnancy , Female , Humans , Azithromycin/adverse effects , Premature Birth/prevention & control , Premature Birth/drug therapy , Anti-Bacterial Agents/adverse effects
10.
Eur Respir Rev ; 31(166)2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2079388

ABSTRACT

Lower respiratory infections include acute bronchitis, influenza, community-acquired pneumonia, acute exacerbation of COPD and acute exacerbation of bronchiectasis. They are a major cause of death worldwide and often affect the most vulnerable: children, elderly and the impoverished. In this paper, we review the clinical presentation, diagnosis, severity assessment and treatment of adult outpatients with lower respiratory infections. The paper is divided into sections on specific lower respiratory infections, but we also dedicate a section to COVID-19 given the importance of the ongoing pandemic. Lower respiratory infections are heterogeneous entities, carry different risks for adverse events, and require different management strategies. For instance, while patients with acute bronchitis are rarely admitted to hospital and generally do not require antimicrobials, approximately 40% of patients seen for community-acquired pneumonia require admission. Clinicians caring for patients with lower respiratory infections face several challenges, including an increasing population of patients with immunosuppression, potential need for diagnostic tests that may not be readily available, antibiotic resistance and social aspects that place these patients at higher risk. Management principles for patients with lower respiratory infections include knowledge of local surveillance data, strategic use of diagnostic tests according to surveillance data, and judicious use of antimicrobials.


Subject(s)
Anti-Infective Agents , Bronchitis , COVID-19 , Community-Acquired Infections , Pneumonia , Respiratory Tract Infections , Adult , Child , Humans , Aged , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Bronchitis/diagnosis , Bronchitis/drug therapy , Pneumonia/diagnosis , Acute Disease , Anti-Infective Agents/therapeutic use , Hospitals , Anti-Bacterial Agents/adverse effects
11.
Gastroenterology ; 163(3): 608-619, 2022 09.
Article in English | MEDLINE | ID: covidwho-2008341

ABSTRACT

BACKGROUND & AIMS: Novel, effective treatments for Helicobacter pylori infection are needed. This study evaluated the efficacy of vonoprazan, a potassium-competitive acid blocker, vs standard treatment on H pylori eradication in the United States and Europe. METHODS: In a randomized, controlled, phase 3 trial, treatment-naïve adults with H pylori infection were randomized 1:1:1 to open-label vonoprazan dual therapy (20 mg vonoprazan twice daily; 1 g amoxicillin 3 times daily), or double-blind triple therapy twice a day (vonoprazan 20 mg or lansoprazole 30 mg; amoxicillin 1 g; clarithromycin 500 mg) for 14 days. The primary outcome was noninferiority in eradication rates in patients without clarithromycin- and amoxicillin-resistant strains (noninferiority margin = 10%). Secondary outcomes assessed superiority in eradication rates in clarithromycin-resistant infections, and in all patients. RESULTS: A total of 1046 patients were randomized. Primary outcome eradication rates (nonresistant strains): vonoprazan triple therapy 84.7%, dual therapy 78.5%, vs lansoprazole triple therapy 78.8% (both noninferior; difference 5.9%; 95% confidence interval [CI], -0.8 to 12.6; P < .001; difference -0.3%; 95% CI, -7.4 to 6.8; P = .007, respectively). Eradication rates in clarithromycin-resistant infections: vonoprazan triple therapy 65.8%, dual therapy 69.6%, vs lansoprazole triple therapy 31.9% (both superior; difference 33.9%; 95% CI, 17.7-48.1; P < .001; difference 37.7%; 95% CI, 20.5-52.6; P < .001, respectively). In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5%, difference 12.3%; 95% CI, 5.7-18.8; P < .001; difference 8.7%; 95% CI, 1.9-15.4; P = .013). Overall frequency of treatment-emergent adverse events was similar between vonoprazan and lansoprazole regimens (P > .05). CONCLUSION: Both vonoprazan-based regimens were superior to proton pump inhibitor-based triple therapy in clarithromycin-resistant strains and in the overall study population. CLINICALTRIALS: gov; NCT04167670.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Adult , Amoxicillin/adverse effects , Anti-Bacterial Agents/adverse effects , Clarithromycin/adverse effects , Drug Therapy, Combination , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Humans , Lansoprazole/adverse effects , Proton Pump Inhibitors/adverse effects , Pyrroles , Sulfonamides , Treatment Outcome , United States/epidemiology
12.
Future Microbiol ; 17: 653-663, 2022 06.
Article in English | MEDLINE | ID: covidwho-1974548

ABSTRACT

Aim: To assess the impact of Clostridioides difficile infection on the course of COVID-19. Methods: The authors included 809 patients with COVID-19 in this retrospective study: 55 had C. difficile infection, 23 had C. difficile-negative antibiotic-associated diarrhea and 731 had no diarrhea. C. difficile in feces was determined by immunochromatographic test for its toxins. Results:C. difficile infection was associated with increased risk of death (hazard ratio = 2.6; p = 0.021), especially after 20 days of disease (hazard ratio = 6.5; p < 0.001). C. difficile infection-associated diarrhea was longer and more severe than C. difficile-negative antibiotic-associated diarrhea. Unlike patients with C. difficile-negative antibiotic-associated diarrhea, patients with C. difficile infection were admitted to the intensive care unit and needed mechanical ventilation more often than those without diarrhea. Conclusion:C. difficile infection worsens the course and prognosis of COVID-19.


Patients with COVID-19 usually receive antibiotic treatment, which predisposes them to antibiotic-associated diarrhea. In some cases, antibiotic-associated diarrhea can be caused by Clostridioides difficile bacteria. To learn more about the impact of C. difficile infection on COVID-19, the authors analyzed data from the medical records of 809 patients with COVID-19. The authors found that C. difficile co-infection worsens the course and prognosis of COVID-19. The authors suggest that patients with COVID-19 who develop diarrhea after taking antibiotics be tested for C. difficile and treated for this co-infection if the test is positive.


Subject(s)
COVID-19 , Clostridioides difficile , Clostridium Infections , Coinfection , Anti-Bacterial Agents/adverse effects , COVID-19/complications , Clostridium Infections/complications , Clostridium Infections/diagnosis , Clostridium Infections/epidemiology , Coinfection/drug therapy , Diarrhea/drug therapy , Humans , Retrospective Studies
14.
Pediatr Pulmonol ; 57(7): 1814-1817, 2022 07.
Article in English | MEDLINE | ID: covidwho-1913872

ABSTRACT

This pilot study successfully implemented a standardized protocol for tablet-based ototoxicity screening in pediatric cystic fibrosis (CF) patients exposed to aminoglycosides. Further studies are needed to assess the impact of implementation in a larger number of patients, as well as to determine barriers that may exist at centers with variation in available resources. This method of ototoxicity screening represents an accessible alternative to traditional audiology testing, and given the continued improvements in expected life span for people with CF, it is imperative that patients have regular access to this type of screening to allow for early identification of medication-related toxicities.


Subject(s)
Audiology , Cystic Fibrosis , Ototoxicity , Aminoglycosides/adverse effects , Anti-Bacterial Agents/adverse effects , Child , Cystic Fibrosis/drug therapy , Humans , Pharmacists , Pilot Projects
15.
Pediatr Allergy Immunol ; 33(6): e13809, 2022 06.
Article in English | MEDLINE | ID: covidwho-1909500

ABSTRACT

BACKGROUND: Mild non-immediate reactions (NIR) to beta-lactams (ßLs) are the most common manifestation of adverse drug reactions in children, and the drug provocation test (DPT) remains the gold standard for diagnosis. However, there are still controversies about the protocol that should be used, especially regarding the administration of doses and the DPT length. OBJECTIVE: This study aimed to evaluate a pediatric population with a history of mild NIR to amoxicillin (AMX) or to amoxicillin-clavulanic acid (AMX/CL) who underwent a diagnostic workup including a DPT with the culprit drug, to understand if a graded DPT or, instead, a single full dose could be the most appropriate way of administration in clinical practice. METHODS: The data of children were retrospectively analyzed for a 5-year period, with demographic and clinical characteristics collected. We reported the allergy workup and the results of the DPT performed with the administration of incremental doses and a prolonged DPT at home for a total of 5 days. RESULTS: Three hundred fifty-four patients were included. Overall, 23/354 (6.5%) DPTs were positive: 11/23 patients showed a reaction after 2-8 h after the last dose on the 1st or 2nd day (1 reacted 30 min after the last dose), 1/23 reacted with urticaria 30 min after the first dose, 11/23 reacted at home on the 5th day of the DPT. CONCLUSION: This paper indirectly suggests that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild NIR to AMX/CL. Moreover, this could be less time-consuming as patients would spend less time in the hospital, also considering the public health restrictions imposed during the COVID-19 pandemic.


Subject(s)
COVID-19 , Drug Hypersensitivity , Amoxicillin/adverse effects , Anti-Bacterial Agents/adverse effects , Child , Drug Hypersensitivity/diagnosis , Humans , Pandemics , Retrospective Studies , Skin Tests/methods , Tertiary Healthcare
16.
JAMA Pediatr ; 176(3): 253-261, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1864300

ABSTRACT

IMPORTANCE: Childhood community-acquired pneumonia (CAP) is usually treated with 10 days of antibiotics. Shorter courses may be effective with fewer adverse effects and decreased potential for antibiotic resistance. OBJECTIVE: To compare a short (5-day) vs standard (10-day) antibiotic treatment strategy for CAP in young children. DESIGN, SETTING, AND PARTICIPANTS: Randomized double-blind placebo-controlled clinical trial in outpatient clinic, urgent care, or emergency settings in 8 US cities. A total of 380 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled from December 2, 2016, to December 16, 2019. Data were analyzed from January to September 2020. INTERVENTION: On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic. MAIN OUTCOMES AND MEASURES: The primary end point was the end-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child's clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR). Within each DOOR rank, participants were further ranked by the number of antibiotic days, assuming that shorter antibiotic durations were more desirable. Using RADAR, the probability of a more desirable outcome was estimated for the short- vs standard-course strategy. In a subset of children, throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. RESULTS: A total of 380 children (189 randomized to short course and 191 randomized to standard course) made up the study population. The mean (SD) age was 35.7 (17.2) months, and 194 participants (51%) were male. Of the included children, 8 were Asian, 99 were Black or African American, 234 were White, 32 were multiracial, and 7 were of unknown or unreported race; 33 were Hispanic or Latino, 344 were not Hispanic or Latino, and 3 were of unknown or unreported ethnicity. There were no differences between strategies in the DOOR or its individual components. Fewer than 10% of children in either strategy had an inadequate clinical response. The short-course strategy had a 69% (95% CI, 63-75) probability of a more desirable RADAR outcome compared with the standard-course strategy. A total of 171 children were included in the resistome analysis. The median (range) number of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with the standard-course strategy for total RGPC (1.17 [0.35-2.43] vs 1.33 [0.46-11.08]; P = .01) and ß-lactamase RGPC (0.55 [0.18-1.24] vs 0.60 [0.21-2.45]; P = .03). CONCLUSIONS AND RELEVANCE: In this study, among children responding to initial treatment for outpatient CAP, a 5-day antibiotic strategy was superior to a 10-day strategy. The shortened approach resulted in similar clinical response and antibiotic-associated adverse effects, while reducing antibiotic exposure and resistance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02891915.


Subject(s)
Community-Acquired Infections , Pneumonia , Anti-Bacterial Agents/adverse effects , Child , Child, Preschool , Community-Acquired Infections/drug therapy , Double-Blind Method , Female , Humans , Male , Outpatients , Pneumonia/drug therapy
17.
Clin Infect Dis ; 75(2): 221-229, 2022 08 25.
Article in English | MEDLINE | ID: covidwho-1852979

ABSTRACT

BACKGROUND: We aimed to determine the noninferiority of fosfomycin compared to ciprofloxacin as an oral step-down treatment for Escherichia coli febrile urinary tract infections (fUTIs) in women. METHODS: This was a double-blind, randomized, controlled trial in 15 Dutch hospitals. Adult women who were receiving 2-5 days of empirical intravenous antimicrobials for E. coli fUTI were assigned to step-down treatment with once-daily 3g fosfomycin or twice-daily 0.5g ciprofloxacin for 10 days of total antibiotic treatment. For the primary end point, clinical cure at days 6-10 post-end of treatment (PET), a noninferiority margin of 10% was chosen. The trial was registered on Trialregister.nl (NTR6449). RESULTS: After enrollment of 97 patients between 2017 and 2020, the trial ended prematurely because of the coronavirus disease 2019 pandemic. The primary end point was met in 36 of 48 patients (75.0%) assigned to fosfomycin and 30 of 46 patients (65.2%) assigned to ciprofloxacin (risk difference [RD], 9.6%; 95% confidence interval [CI]: -8.8% to 28.0%). In patients assigned to fosfomycin and ciprofloxacin, microbiological cure at days 6-10 PET occurred in 29 of 37 (78.4%) and 33 of 35 (94.3%; RD, -16.2%; 95% CI: -32.7 to -0.0%). Any gastrointestinal adverse event was reported in 25 of 48 (52.1%) and 14 of 46 (30.4%) patients (RD, 20.8%; 95% CI: 1.6% to 40.0%), respectively. CONCLUSIONS: Fosfomycin is noninferior to ciprofloxacin as oral step-down treatment for fUTI caused by E. coli in women. Fosfomycin use is associated with more gastrointestinal events. CLINICAL TRIAL REGISTRATION: Trial NL6275 (NTR6449).


Subject(s)
COVID-19 , Escherichia coli Infections , Fosfomycin , Urinary Tract Infections , Adult , Anti-Bacterial Agents/adverse effects , Ciprofloxacin/therapeutic use , Double-Blind Method , Escherichia coli , Escherichia coli Infections/complications , Escherichia coli Infections/drug therapy , Female , Fever/drug therapy , Fosfomycin/adverse effects , Humans , Urinary Tract Infections/microbiology
18.
Trials ; 23(1): 427, 2022 May 21.
Article in English | MEDLINE | ID: covidwho-1849770

ABSTRACT

BACKGROUND: Inappropriate antibiotic use can cause harm and promote antimicrobial resistance, which has been declared a major health challenge by the World Health Organization. In Australian residential aged care facilities (RACFs), the most common indications for antibiotic prescribing are for infections of the urinary tract, respiratory tract and skin and soft tissue. Studies indicate that a high proportion of these prescriptions are non-compliant with best prescribing guidelines. To date, a variety of interventions have been reported to address inappropriate prescribing and overuse of antibiotics but with mixed outcomes. This study aims to identify the impact of a set of sustainable, multimodal interventions in residential aged care targeting three common infection types. METHODS: This protocol details a 20-month stepped-wedge cluster-randomised trial conducted across 18 RACFs (as 18 clusters). A multimodal multi-disciplinary set of interventions, the 'AMS ENGAGEMENT bundle', will be tailored to meet the identified needs of participating RACFs. The key elements of the intervention bundle include education for nurses and general practitioners, telehealth support and formation of an antimicrobial stewardship team in each facility. Prior to the randomised sequential introduction of the intervention, each site will act as its own control in relation to usual care processes for antibiotic use and stewardship. The primary outcome for this study will be antibiotic consumption measured using defined daily doses (DDDs). Cluster-level rates will be calculated using total occupied bed numbers within each RACF during the observation period as the denominator. Results will be expressed as rates per 1000 occupied bed days. An economic analysis will be conducted to compare the costs associated with the intervention to that of usual care. A comprehensive process evaluation will be conducted using the REAIM Framework, to enable learnings from the trial to inform sustainable improvements in this field. DISCUSSION: A structured AMS model of care, incorporating targeted interventions to optimise antimicrobial use in the RACF setting, is urgently needed and will be delivered by our trial. The trial will aim to empower clinicians, residents and families by providing a robust AMS programme to improve antibiotic-related health outcomes. TRIAL REGISTRATION: US National Library of Medicine Clinical Trials.gov ( NCT04705259 ). Prospectively registered in 12th of January 2021.


Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , Aged , Anti-Bacterial Agents/adverse effects , Anti-Infective Agents/adverse effects , Antimicrobial Stewardship/methods , Australia , Humans , Inappropriate Prescribing/prevention & control , Randomized Controlled Trials as Topic
19.
Am J Health Syst Pharm ; 79(Suppl 2): S43-S52, 2022 05 24.
Article in English | MEDLINE | ID: covidwho-1830988

ABSTRACT

PURPOSE: Current literature surrounding management of patients with reported ß-lactam allergies focuses on allergy delabeling. Standard clinical decision support tools have not been optimized to be compatible with the currently accepted cross-reaction rate of 1% to 2%. This potentially promotes use of non-ß-lactam antibiotics, which are often not first-line therapy and may carry increased risks. The impact of electronic medical record (EMR) clinical decision support tool optimization on utilization of ß-lactam antibiotics in ß-lactam-allergic patients was evaluated. METHODS: A retrospective pre-post ß-lactam cross-allergy EMR alert suppression quality improvement intervention cohort study of ß-lactam-allergic adult inpatients prescribed antibiotics was conducted. Preintervention baseline data were collected for an initial cohort admitted during September 2018. The intervention, in which clinical decision support rules were updated to display ß-lactam cross-sensitivity allergy alerts only for ß-lactam-allergic patients with documentation of organization-defined high-severity reactions of anaphylaxis, hives, and shortness of breath, was implemented August 20, 2019. The postintervention cohort included patients admitted during September 2019. RESULTS: A 91% increase in the percentage of ß-lactam-allergic patients who received a ß-lactam agent at any time during their admission was noted after the intervention (26.6% vs 51%, P < 0.001). Statistically significant decreases in prescribing of alternative antibiotic classes were seen for fluoroquinolones (decrease from 45.3% to 26%, P < 0.001), aminoglycosides (decrease from 9.4% to 2.9%, P = 0.002), and aztreonam (decrease from 30% to 16.7%, P < 0.001). CONCLUSION: EMR ß-lactam cross-allergy alert optimization consistent with current literature significantly improved the utilization of alternative ß-lactam subclasses, mostly through ß-lactam prescribing as initial therapy in ß-lactam-allergic patients.


Subject(s)
Drug Hypersensitivity , beta-Lactams , Adult , Anti-Bacterial Agents/adverse effects , Cohort Studies , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/epidemiology , Drug Hypersensitivity/prevention & control , Electronic Health Records , Humans , Penicillins , Retrospective Studies , beta-Lactams/adverse effects
20.
J Anesth ; 36(3): 432-435, 2022 06.
Article in English | MEDLINE | ID: covidwho-1826493

ABSTRACT

Prolonged neurological symptoms such as "brain fog" and cognitive impairment have occurred after coronavirus disease 2019 (COVID-19) infection. In this report, we describe impaired consciousness caused by cefepime hydrochloride (CFPM) in a patient with cognitive sequalae of COVID-19. A 56-year-old male patient was diagnosed with penile abscess after COVID-19 infection, and a blood culture detected two drug-resistant Pseudomonas aeruginosa strains. Therefore, CFPM 2 g × twice/day was administered on day 71 after intensive care unit admission. Approximately 48 h after CFPM administration, the patient showed disturbances in consciousness. Contrast-enhanced computed tomography, magnetic resonance imaging, and spinal fluid examination revealed no obvious abnormalities. Therefore, CFPM-induced neurotoxicity was suspected. CFPM was discontinued and ceftazidime 2 g × three times/day was initiated. The patient's consciousness improved 30 h after the final administration of CFPM. Serum CFPM concentrations were 14.2, 21.7, 21.7, and 11.9 µg/mL on days 1, 2, and 3 after the initiation of CFPM and on the day after CFPM was discontinued, respectively. In conclusion, intensivists should pay attention to new neurological symptoms such as CFPM-induced encephalopathy in patients with prolonged neurological symptoms after COVID-19 infection.


Subject(s)
Brain Diseases , COVID-19 Drug Treatment , COVID-19 , Anti-Bacterial Agents/adverse effects , Brain Diseases/chemically induced , Brain Diseases/diagnostic imaging , COVID-19/complications , Cefepime/adverse effects , Cephalosporins/adverse effects , Humans , Male , Middle Aged
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