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1.
Jundishapur Journal of Microbiology ; 15(2):932-944, 2022.
Article in English | GIM | ID: covidwho-2251269

ABSTRACT

Children are usually affected by pneumonia, which is a common ailment caused by Pathogenic Streptococcus pneumoniae. This study's objective was to isolate and identify S. pneumoniae, which was recovered from blood samples of suspected paediatric pneumonia patients using conventional techniques, such as antibiotic sensitivity profiles and molecular approaches. In this study, forty (40) samples from three major hospitals in the Dinajpur region of Bangladesh were collected and assessed using various bacteriological, biochemical, antibiotic susceptibility test, and molecular techniques. 37.5% of the 40 samples tested positive for pneumonia, and 15 isolates were discovered. In terms of age, pneumonia was more common in children aged 3-5 years (50%) than in those aged 6 to 8 (33.33%), 9 to 11 (25%) and 12 to 15 (20%). According to the results of the current study, the study area had no statistically significant impact (P > 0.05), while age and socioeconomic status had a significant impact on the prevalence of pneumonia in patients with pneumonia (P 0.05). The age group for which pneumonia was most prevalent (at 50%) was that for children between the ages of 3-5. Poor socioeconomic status was associated with the highest prevalence of pneumonia (54.54%). By sequencing the 16S rRNA gene, S. pneumoniae was identified as S. pneumoniae NBRC102642. In the antibiotic investigation, S. pneumoniae was found to be extremely resistant to ciprofloxacin, amikacin, vancomycin, and cefexime, but responsive to erythromycin and azithromycin, as well as neomycin, kanamycin, streptomycin, and bacitracin. S. pneumoniae causes serious complications in paediatric patients, and this scenario requires prevention through vaccination and the development of new, efficient antibiotic therapies for pneumonia. If specific laboratory features of paediatric patients with pneumonia are understood, sepsis will be easier to detect early, treat, and reduce mortality.

2.
Antibiotics (Basel) ; 12(2)2023 Jan 20.
Article in English | MEDLINE | ID: covidwho-2270857

ABSTRACT

Monitoring antibiotic use in the pediatric population is a challenge, especially when determining a relationship between specific pathogens, infections, and antibiotic use. We retrospectively analyzed the consumption of anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs from 2017 to 2021 at Istituto Giannina Gaslini by means of defined daily dose (DDD) adopted for adults by World Health Organization. We observed a statistically significant increase in the use of daptomycin and ceftaroline, combined with a decrease in the use of vancomycin. In the same period, we observed an increase in the proportion of bloodstream infections due to MRSA with vancomycin minimally inhibitory concentration (MIC mg/L) = 1, that represented the 100% of cases in 2021. This aspect was combined with the observation that in the 59% of cases, where vancomycin plasma concentrations were evaluated, it was not possible to achieve a ratio of the 24-h area under the concentration-time curve and MIC (AUC0-24/MIC) of vancomycin ≥ 400 mg/L. This study confirms that DDD can be used in pediatrics to monitor antibiotic consumption in relationship with infections epidemiology. Moreover, it describes the presence of vancomycin MIC creep for MRSA also in pediatrics and the difficulties in obtaining effective vancomycin plasma concentrations in children.

3.
Current Problems in Cardiology ; 48(1), 2023.
Article in English | Scopus | ID: covidwho-2239181

ABSTRACT

In the COVID-19 pandemic, to minimize aerosol-generating procedures, cardiac magnetic resonance imaging (CMR) was utilized at our institution as an alternative to transesophageal echocardiography (TEE) for diagnosing infective endocarditis (IE). This retrospective study evaluated the clinical utility of CMR for detecting IE among 14 patients growing typical microorganisms on blood cultures or meeting modified Duke Criteria. Seven cases were treated for IE. In 2 cases, CMR results were notable for possible leaflet vegetations and were clinically meaningful in guiding antibiotic therapy, obtaining further imaging, and/or pursuing surgical intervention. In 2 cases, vegetations were missed on CMR but detected on TEE. In 3 cases, CMR was non-diagnostic, but patients were treated empirically. There was no difference in antibiotic duration or outcomes over 1 year. CMR demonstrated mixed results in diagnosing valvular vegetations and guiding clinical decision-making. Further prospective controlled trials of CMR Vs TEE are warranted. © 2022 Elsevier Inc.

4.
Infectious Disease Alert ; 42(4):45261.0, 2023.
Article in English | CINAHL | ID: covidwho-2238073

ABSTRACT

The article discusses the retrospective cohort study performed at the Mayo Clinic in Minnesota from February to June 2022, the first peer-reviewed publication demonstrating the efficacy of the monoclonal antibody bebtelovimab in the prevention of severe COVID-19 infection compared with nirmatrelvir/ritonavir. It mentions that the Food and Drug Administration has issued emergency use authorizations for six new monoclonal antibodies in the fight against SARS-CoV-2.

5.
Cureus ; 14(10): e30521, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2145101

ABSTRACT

A 71-year-old female presented to the emergency department with worsening dyspnea, dry cough, malaise, weight loss, fever, chills, and diaphoresis for one week. The patient had been hospitalized four weeks prior with right knee methicillin-resistant Staphylococcus aureus (MRSA) bursitis and was initially treated with IV vancomycin but was switched to IV daptomycin at the time of discharge for convenience of dosing. On presentation to the ED, vitals were normal. Physical examination revealed bilateral scattered rhonchi and crepitations. Chest X-ray revealed new patchy bilateral interstitial and airspace opacities concerning for multifocal pneumonia. Labs were pertinent for mild peripheral eosinophilia. CT chest revealed moderate diffuse ground glass opacities involving both lungs, with subpleural predominance and some areas of septal thickening seen as well. Daptomycin-induced pneumonitis was suspected, and empiric antibiotics were discontinued. The patient subsequently underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsy. BAL fluid showed leukocytosis and eosinophilia of 25 mm3. Right upper lobe biopsy demonstrated foci of alveolar spaces with collections of eosinophils and histiocytes consistent with acute eosinophilic pneumonia. The patient was started on oral prednisone and albuterol breathing treatments with significant improvement after 48 hours from admission. She was discharged on albuterol inhalers and prednisone taper. Acute eosinophilic pneumonia (AEP) is a lung condition that can be rapidly progressive, leading to significant morbidity and mortality. Daptomycin-induced AEP can mimic community-acquired pneumonia, resulting in delayed diagnosis and management. Recognizing the temporal association between drug initiation and the development of symptoms is crucial in the diagnosis of drug-induced AEP. If it is recognized and treated in a timely manner, the prognosis is generally excellent, with rapid and complete clinical recovery as demonstrated by our case.

6.
Chest ; 162(4):A1868, 2022.
Article in English | EMBASE | ID: covidwho-2060878

ABSTRACT

SESSION TITLE: Drug-Induced Lung Injury Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Acute eosinophilic pneumonia (AEP) is an atypical cause of acute hypoxic respiratory failure in adults, however if not identified can prove to be fatal. It can all be a COVID19 mimic during the pandemic. AEP has several causes, such as inhalational drugs, infections and various pharmaceuticals. Often, patients will have an acute respiratory syndrome for less than one-month, pulmonary infiltrates on chest computed tomography (CT) or radiography (CXR), in addition to bronchoalveolar lavage (BAL) with more than 25% of eosinophils. CASE PRESENTATION: A 79 y/o man underwent an elective total knee replacement complicated by acute lower limb ischemia from an occluded bypass graft. He developed methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE) joint and soft tissue infection of the lower extremity. He was prescribed a 6-week course of Daptomycin. He presented about 3 weeks into treatment with shortness of breath. He was initially diagnosed with acute on chronic congestive heart failure (CHF) exacerbation and COVID negative. He was initially treated with diuretics. He developed acute renal failure requiring dialysis and acute hypoxic respiratory failure requiring intubation. CXR revealed bilateral lung infiltrates with BAL having 80% eosinophils, eosinophilia and urinalysis positive for eosinophils. Daptomycin was discontinued and he was started on systemic steroids for a two-week course. He was successfully extubated 5 days after diagnosis of AEP and was subsequently discharged to a rehabilitation facility on lifelong Doxycycline for MRSA prosthetic joint infection prophylaxis. DISCUSSION: AEP related to Daptomycin was first reported in 2007, in a patient that developed the condition after receiving treatment for endocarditis. Daptomycin caused an inflammatory reaction within the lungs, due to an accumulation of the drug within the pulmonary surfactant. Our case report patient met all components for AEP diagnosis, in addition to symptom onset being approximately 3 weeks into treatment. The ultimate treatment for AEP is to stop the reversible cause, if identifiable, along with glucocorticoids and symptomatic support. Prognosis for patients with AEP is excellent when diagnosis is prompt, and usually infiltrates are resolved within 1 month without long term adverse pulmonary effects. Our patient was discharged to an acute rehab facility without supplemental oxygen therapy and continues to improve from functional standpoint. This case a definite cause of AEP from Daptomycin presented as COVID19 pneumonia mimic. It highlights the importance of rapid diagnosis to prevent morbidity and mortality. CONCLUSIONS: The differential in a patient with acute hypoxic respiratory failure is numerous, especially during the COVID19 pandemic. During these challenging times, it is important to think of atypical causes, such as AEP to improve the patient's clinical status. Reference #1: Allen JN, Pacht ER, Gadek JE, Davis WB. Acute Eosinophilic Pneumonia as a Reversible Cause of Noninfectious Respiratory Failure. N Engl J Med. 1989;321:569-574 Reference #2: Hayes Jr. D, Anstead MI, Kuhn RJ. Eosinophilic pneumonia induced by daptomycin. J Infect. 2007;54(4):e211-213. Reference #3: Rachid M, Ahmad K, Saunders-Kurban M, Fatima A, Shah A, Nahhas A. Daptomycin-Induced Acute Eosinophilic Pneumonia: Late Onset and Quick Recovery. Case Reports in Pulmonology. 2017. DISCLOSURES: No relevant relationships by Moses Bachan No relevant relationships by Zinobia Khan No relevant relationships by Kaitlyn Mehern

7.
Chest ; 162(4):A1773, 2022.
Article in English | EMBASE | ID: covidwho-2060858

ABSTRACT

SESSION TITLE: Drug-Induced Lung Injury Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Daptomycin is an antibiotic that exerts its bactericidal effect by disrupting multiple aspects of bacterial cell membrane function. It has notable adverse effects including myopathy, rhabdomyolysis, eosinophilic pneumonitis, and anaphylactic hypersensitivity reactions. CASE PRESENTATION: A 46-year-old male with a history of type 2 diabetes presented with a 1-week history of dyspnea and productive cough. 2 weeks prior, he was started on vancomycin for MRSA osteomyelitis of the right foot, but was switched to daptomycin due to vancomycin induced nephrotoxicity. On presentation he was afebrile, tachycardic 100, hypertensive 183/109, tachypneic to 26, hypoxemic 84% on room air, which improved to 94% on nasal cannula. Chest exam noted coarse breath sounds in all fields and pitting edema of lower extremities were present. Labs showed leukocytosis of 15.2/L, Na of 132 mmol/L, and creatinine 3.20mg/dL (normal 1 month prior). COVID-19 testing was negative. Chest X-ray noted new bilateral asymmetric opacifications. Daptomycin was discontinued on day 1 of admission, he was started on IV diuretics and ceftaroline. Further study noted peripheral eosinophilia. Computed tomography of the chest showed bilateral centrally predominant ground-glass infiltrates with air bronchograms and subcarinal and paratracheal lymphadenopathy. On day 4, he underwent bronchoscopy with bronchoalveolar lavage. Cytology noted 4% eosinophil with 43% lymphocytes. Eventually, oxygen requirements and kidney function returned to baseline. He was discharged on ceftaroline for osteomyelitis DISCUSSION: Daptomycin-induced acute eosinophilic pneumonitis (AEP) often results in respiratory failure in the setting of exposure to doses of daptomycin >6mg/kg/day. It is characterized by the infiltration of pulmonary parenchyma with eosinophils and is often associated with peripheral eosinophilia. AEP has been associated with certain chemicals, non-steroidal anti-inflammatory agents, and antibiotics including daptomycin. Renal dysfunction is associated with an increased risk for developing AEP. The mechanism for daptomycin-induced lung injury is unknown but is believed to be related to daptomycin binding to pulmonary surfactant culminating in epithelial injury. Diagnostic criteria include recent daptomycin exposure, fever, dyspnea with hypoxemic respiratory failure, new infiltrates on chest radiography, BAL with > 25% eosinophils, and clinical improvement following daptomycin discontinuation. Our patient met four out of six criteria;we believe that BAL results were due to discontinuing daptomycin days before the procedure was performed. Sometimes stopping daptomycin is enough for recovery, however, steroids may be beneficial and were used in some of the cases reported in the literature CONCLUSIONS: Clinicians should consider AEP in a patient on Daptomycin presenting with respiratory failure, as timely discontinuation favors a good prognosis Reference #1: Uppal P, LaPlante KL, Gaitanis MM, Jankowich MD, Ward KE. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control. 2016;5:55. Published 2016 Dec 12. doi:10.1186/s13756-016-0158-8 Reference #2: Kumar S, Acosta-Sanchez I, Rajagopalan N. Daptomycin-induced Acute Eosinophilic Pneumonia. Cureus. 2018;10(6):e2899. Published 2018 Jun 30. doi:10.7759/cureus.2899 Reference #3: Bartal C, Sagy I, Barski L. Drug-induced eosinophilic pneumonia: A review of 196 case reports. Medicine (Baltimore). 2018;97(4):e9688. doi:10.1097/MD.0000000000009688 DISCLOSURES: No relevant relationships by Chika Winifred Akabusi No relevant relationships by Shazia Choudry No relevant relationships by Hector Ojeda-Martinez No relevant relationships by Mario Torres

8.
Chest ; 162(4):A1286, 2022.
Article in English | EMBASE | ID: covidwho-2060794

ABSTRACT

SESSION TITLE: Critical Diffuse Lung Disease Cases 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Acute eosinophilic pneumonia (AEP) is dramatic in presentation mimicking infectious pneumonia or acute respiratory distress syndrome in previously healthy individuals. Medications are a commonly recognized cause of AEP. Daptomycin, has been strongly linked to AEP. Herein, we present a case of a patient with a septic joint treated with Daptomycin who went on to develop AEP. CASE PRESENTATION: Patient is an 80 year old man with history of hypertension, hypothyroidism, atrial flutter, complete heart block status post pacemaker, who had a hx of a mucinous cyst on his left index finger, requiring hospitalization. Blood cultures were positive for MRSA s/p debridement of the joint. He was discharged on 4 weeks of intravenous daptomycin. Two weeks after being discharged he presented back to the hospital with fevers, fatigue and worsening shortness of breath. His temperature was 103.8 and O2 saturation of 90% on 2L NC. Laboratory findings included WBC count of 8.6 with no eosinophilia on differential, ESR 110, negative blood cultures, sputum cultures with commensal flora, negative urine legionella, PCR for SARS COV-2 was negative. Chest radiograph showed mild interstitial airspace disease in the left mid and lower thorax, along with small bilateral pleural effusions. CT chest showed scattered bilateral consolidations and ground glass opacities and trace bilateral effusions. Daptomycin was switched to Vancomycin. Patients oxygen requirements had increased to 6l NC. Patient underwent airway exam with bronchoscopy and broncheoalveolar lavage in superior segment of the lingula, which showed inflamed bronchial mucosa with copious secretions. Cell count of the BAL showed increased eosinophil count with negative gram stain and culture. Patient was started on methylprednisolone 60 mg four times per day and then tapered. Vancomycin was switched to oral linezolid. Patient's hypoxia improved and was discharged home on 3l NC. At four week follow up, he no longer required oxygen on ambulation and chest radiograph showed complete resolution of infiltrates. DISCUSSION: Over 140 drugs have been recognized as a cause of drug induced eosinophilic pneumonia (DIEP). The diagnosis of DIEP requires febrile illness <5 days, diffuse bilateral infiltrates, hypoxemia and BAL showing 25% eosinophils or eosinophilic pneumonitis on lung biopsy. Additionally, a diagnosis of DIEP requires exposure to a candidate drug in the appropriate time frame, exclusion of infectious causes of eosinophilic pulmonary opacities. It also requires clinical improvement after cessation of medication. Daptomycin has been strongly linked to DIEP. In 2010 US FDA issued a warning about the risk of developing eosinophilic pneumonia during treatment with Daptomycin. CONCLUSIONS: Daptomycin is strongly linked with DIEP. Clinicians should maintain a high index of suspicion for DIEP in patient treated with daptomycin who develop respiratory distress. Reference #1: Uppal, P., LaPlante, K.L., Gaitanis, M.M. et al. Daptomycin-induced eosinophilic pneumonia - a systematic review. Antimicrob Resist Infect Control 5, 55 (2016). https://doi.org/10.1186/s13756-016-0158-8 Reference #2: Cottin V. Eosinophilic Lung Diseases. Clin Chest Med. 2016 Sep;37(3):535-56. doi: 10.1016/j.ccm.2016.04.015. Epub 2016 Jun 25. PMID: 27514599. Reference #3: Rosenberg CE, Khoury P. Approach to Eosinophilia Presenting With Pulmonary Symptoms. Chest. 2021 Feb;159(2):507-516. doi: 10.1016/j.chest.2020.09.247. Epub 2020 Sep 28. PMID: 33002503;PMCID: PMC8039005. DISCLOSURES: No relevant relationships by Kamelia Albujoq No relevant relationships by Rajaninder Sharma

9.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927727

ABSTRACT

Introduction: Daptomycin is an antibiotic approved by FDA in 2003 with an excellent coverage for Gram positive cocci including methicillin resistant Staph. Aureus and vancomycin resistant Enterococci.Acute Eosinophilic Pneumonia(AEP) is a rare but potentially fatal complication of daptomycin is characterized by febrile illness, Hypoxemia,Diffuse Bilateral pulmonary infiltrates and BAL with >25% eosinophils. Case Report: 79 Y/O M with the CKD stage 4 and hypertension presented to the hospital with fever, dry cough and worsening shortness of breath after a recent hospital admission for MRSA bacteremia.Patient was admitted 1 week before presentation for symptoms of pyelonephritis and was found to have MRSA bacteremia for which he was discharged on IV daptomycin for 6 weeks. On admission,patient was febrile with hypoxic to 81%. Labs did show leukocytosis with mild peripheral eosinophilia.PCR for respiratory viruses including covid was negative.Chest X ray was done, which was consistent with multifocal Pneumonia which was followed by Chest CT scan which demonstrated new bilateral dense ground-glass and consolidative opacities.Given concerns for aspiration pneumonia, fungal infections or eosinophilic pneumonitis,pulmonology was consulted for possible bronchoscopy.Bronchoscopy with BAL was done the next day.BAL revealed a WBC of 260/μL with 45% eosinophilic predominance. Given the bronchoscopy results,his symptoms were attributed to Daptomycin related eosinophilic pneumonia.Patient was started on 40mg oral prednisone for a total of 4 weeks with rapid taper.Over the hospital course, his symptoms completely resolved. Discussion: The prosed mechanism involves presentation of drug or drug-hapten combination by the macrophages to the T helper cell results in interleukin-5 release which along with macrophage released eotaxin, results in eosinophilic migration to lungs.The criteria for to diagnose AEP due to daptomycin consist of 4 components which includes febrile illness,hypoxemia,diffuse bilateral pulmonary infiltrates and BAL with >25% eosinophils.Peripheral eosinophilia may not be present in all cases. It is also possible that daptomycin, a renally excreted drug, persists in the lungs of patients with renal dysfunction as seen in our patient and as such may lead to higher incidence of daptomycin induced AEP.In most cases, a short course of steroids(2-3 weeks)is sufficient for complete resolution of symptoms. Conclusion: Daptomycin induced AEP is increasingly seen in patients with high doses of drug and underlying renal dysfunction,and not related to therapy duration as it can occur as early as day 3 of treatment and as late as week 6 of treatment course. Bronchoscopy with BAL should be considered in all cases suspected. (Figure Presented).

10.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927725

ABSTRACT

Introduction: The known etiologies of acute eosinophilic pneumonia (AEP) have grown recently, culminating in the creation of the term drug-induced AEP 3. One of the newer causes of druginduced AEP is Daptomycin, which has grown in popularity for its use in treating methicillin-resistant staph aureus (MRSA) infections. As a result, the Food Drug Administration created the following criteria to diagnosis Daptomycin-induced AEP: 1) concurrent exposure to Daptomycin, 2) fever, 3) dyspnea with increased oxygen requirement or requiring mechanical ventilation, 4) new infiltrates on imaging, 5) bronchoalveolar lavage (BAL) with >25% eosinophils and 6) clinical improvement following Daptomycin withdrawal. Given this statement, we present a case of Daptomycin-induced AEP. Case Presentation: A 45-year old female presented to the ER with a complaint of shortness of breath for four days. She had recently been diagnosed with Covid-19 with concomitant globicatella bacteremia and discharged 17 days ago with home oxygen (requiring 3L) and to complete 2 weeks of IV Daptomycin. In the ER, a CT Angio Chest was obtained showing bilateral airspace opacities with no evidence of thromboembolism. She was also noted to be saturating at 92% while on 15L Venturi-mask. The patient was started on broad-spectrum antibiotics and cultures were obtained. Her condition worsened and a bronchoscopy with bronchoalveolar lavage (BAL) was performed, however there was inadequate specimen to run cytology. Due to worsening status despite antibiotics, the patient was started on methylprednisolone 80 mg three times a day. After initiation of steroids, the patient's respiratory status returned to baseline and repeat imaging showed improvements of opacities. Complete infectious and autoimmune workups were complete ruling out other etiologies. The patient was discharged with a steroid taper and repeat CT imaging ordered, but never done. Discussion: Though we were unable to obtain a BAL specimen, we are confident of our diagnosis. Our patient not only had a known inciting factor, but also had resolution of symptoms with withdrawal of Daptomycin and initiation of steroids. Our case study highlights two important points about the disease. First, AEP should be on the differential for patients with a complaint of shortness of breath with a known inciting factor. Secondly, it should be noted that while our patient was unable to meet all criteria created by the FDA, this should not rule out the diagnosis. It is important to be proactive in treatment if clinical suspicion is high.

11.
Comput Struct Biotechnol J ; 20: 2442-2454, 2022.
Article in English | MEDLINE | ID: covidwho-1894921

ABSTRACT

Cathepsin L (CTSL), a cysteine protease that can cleave and activate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, could be a promising therapeutic target for coronavirus disease 2019 (COVID-19). However, there is still no clinically available CTSL inhibitor that can be used. Here, we applied Chemprop, a newly trained directed-message passing deep neural network approach, to identify small molecules and FDA-approved drugs that can block CTSL activity to expand the discovery of CTSL inhibitors for drug development and repurposing for COVID-19. We found 5 molecules (Mg-132, Z-FA-FMK, leupeptin hemisulfate, Mg-101 and calpeptin) that were able to significantly inhibit the activity of CTSL in the nanomolar range and inhibit the infection of both pseudotype and live SARS-CoV-2. Notably, we discovered that daptomycin, an FDA-approved antibiotic, has a prominent CTSL inhibitory effect and can inhibit SARS-CoV-2 pseudovirus infection. Further, molecular docking calculation showed stable and robust binding of these compounds with CTSL. In conclusion, this study suggested for the first time that Chemprop is ideally suited to predict additional inhibitors of enzymes and revealed the noteworthy strategy for screening novel molecules and drugs for the treatment of COVID-19 and other diseases with unmet needs.

12.
Indian Journal of Pharmaceutical Education and Research ; 56(2):S121-S136, 2022.
Article in English | EMBASE | ID: covidwho-1884616

ABSTRACT

Drug repurposing is the remodeling of already existing drugs to reduce the time frame, costs, and efforts in developing a new novel drug. This strategy has secured significant momentum in the previous decade. It overcomes the snags and pitfalls in the traditional means of drug discovery. This core research strategy has now become the sole approach to containing many deadly diseases that have no cure in the present. In astound, for pandemics like COVID-19 that is spreading like a wildfire worldwide, large-scale research programs and trials have been carried out to identify and modify existing drugs to counter the novel virus. Thus, this technology of drug repurposing offers a new lease of life, and greatly promotes the progress of the medicine, health, and pharma sectors. The purpose of this study is to understand the current status of drug repurposing in the field of virology, bacteriology, mycology, and oncology for clinical translatability.

13.
Kidney International Reports ; 7(2):S230-S231, 2022.
Article in English | EMBASE | ID: covidwho-1703781

ABSTRACT

Introduction: Phosphorus is an essential component of many macromolecules found in bone, lipid membranes, and DNA. It circulates in serum as phosphate. Phosphate level is mainly determined by kidney function. Other factors such as 1, 25 vitamin D3, thyroid hormone and low phosphorous intake can increase renal absorption of phosphate. Hyperphosphatemia presents when serum phosphate is above 4.5 mg/dl (1.45 mmol/L). The phosphate target for hemodialysis (HD) patients is 5.5 mg/dl (1.77 mmol/L) or less. Serum phosphate is commonly measured through the colorimetric method and can also be measured isotopically. Depending on the method used to measure the serum phosphate, many factors have been reported to produce falsely elevated levels. Methods: 52-year-old female with past medical history of end stage renal disease on HD, heart failure with severely reduced ejection fraction secondary to ischemic cardiomyopathy status post left ventricular assist device (LVAD), type 2 diabetes, hypertension, upper gastrointestinal bleeding, anemia, was admitted at a rehabilitation center after a hospital stay due to COVID-19 infection and E. faecium bacteremia secondary to a drive-line infection of the LVAD which was treated with daptomycin. On admission, the patient was found to have a phosphorus level of 6.3 mg/dl, PTH 265 pg/mL, corrected calcium 10 mg/dl, and hemoglobin 9.1 g/dL. Results: Patient was started on oral Sevelamer tablets 800 mg every 8 hours and underwent regular full HD sessions. However, the hyperphosphatemia persisted. Sevelamer was increased to 1600 mg every 8 hours, and she was maintained on a strict low phosphorous renal diet. Four days later while on the new regimen, the phosphorous increased to 12.2 mg/dl. She remained asymptomatic. Hemolysis and hyperbilirubinemia were excluded. A serum protein electrophoresis revealed a monoclonal spike in the gamma region with gamma % of 38.5 (normal range 11-20), gamma globulin 3.0 g/dL (normal range 0.6 – 1.6 g/dL), and quantification of the abnormal protein of 0.41 g/dL (5.3% total). Serum immunofixation showed a probable IgG Lambda monoclonal band. A serum free light chain assay demonstrated a Kappa light chain free serum of 548.9 mg/L (normal range 3.3 – 19.4 mg/L) and Lambda light chain free serum 549.7 mg/L (normal range 5.7 – 26.3 mg/L). Patient was diagnosed with a monoclonal gammopathy, and the elevated phosphorus deemed to be pseudohyperphosphatemia secondary to paraproteinemia. Conclusions: Colorimetric assay with phosphomolybdate ultraviolet (UV) is commonly used for measurement of serum phosphate. The ammonium molybdate reacts with the phosphate to form a cloudy complex, UV absorbance is measured at a specific wavelength. Several factors have been reported to cause falsely high phosphate such as hyperlipidemia, hyperbilirubinemia, hemolysis, liposomal amphotericin B, recombinant tissue plasminogen activator, heparin sulfate, and gammopathies. The paraproteinemia present in monoclonal gammopathies creates a cloudier sample which increases the absorbance of UV light leading to spurious elevation of serum phosphate. Although hyperphosphatemia is a common finding in dialysis patients, the presence of persisting or worsening hyperphosphatemia in a compliant patient taking phosphorous binders and adhering to a low phosphorus diet should raise concern for pseudohyperphosphatemia. No conflict of interest

14.
Cureus ; 13(6): e16002, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1308540

ABSTRACT

Multifocal pneumonia amidst this global pandemic is often attributed to COVID-19, resulting in missed diagnosis of other potentially fatal illnesses such as eosinophilic pneumonia. Eosinophilic pneumonia is often associated with antibiotics and non-steroidal anti-inflammatory drugs. A 65-year-old male presented to the emergency department for a four-day history of fatigue, cough, and worsening dyspnea; CT thorax showed extensive multifocal pneumonia, and COVID-19 was suspected. COVID-19 testing using reverse transcription polymerase chain reaction was negative, and complete blood count revealed peripheral eosinophilia, which is not expected in COVID-19. The patient was being treated concomitantly with daptomycin and ceftaroline for septic arthritis and methicillin-resistant Staphylococcus aureus bacteremia. We reconsidered our initial diagnosis and held daptomycin, after which the patient started to improve. Due to hypoxia, steroids were added, which resulted in a dramatic improvement of the patient's symptoms. Daptomycin can have toxic effects, resulting in the accumulation of eosinophils in the lung parenchyma. Symptoms usually arise by the third week and include dyspnea, peripheral eosinophilia, and infiltrates involving the outer one-third of the lung fields. FDA drug safety guidance helped to establish this diagnosis. The treatment options include the removal of offending agents and steroids in severe cases.

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