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CASE: An 81-year-old female with multiple co-morbidities including recent covid-19, presented to the emergency room with shortness of breath. On arrival, she was febrile with a temperature of 101F, pulse 100 beats/min, respiratory rate 14, blood pressure 196/163 and saturating at 75% on 10 L non-rebreather mask. Initial blood work showed WBC 10.9, lactic acid 1.7, BUN/creatinine 27/1.7 (consistent with her baseline), ABG showed pH 7.37, PCO2 49, PO2 88, HCO3 27.9. Chest x-ray demonstrated volume loss in the left hemithorax, airspace disease in the left mid lung and lung base. Due to suspicion for superimposed bacterial pneumonia and positive blood cultures for staphylococcus haemolyticus, she was started on vancomycin and azithromycin. Choice of antibiotics was challenging as she was allergic to penicillin and cephalosporins. During hospitalization, her kidney function deteriorated, vancomycin was substituted with tigecycline on day 3. Day 5 of treatment, she developed multiple episodes of vomiting with epigastric pain, lipase was 4523. Acute pancreatitis was diagnosed with tigecycline presumed to be the inciting agent in the absence of other risk factors such as gall stones, chronic alcohol use, elevated triglycerides, previous known episodes of pancreatitis or any other causative medications. Tigecycline was switched back to vancomycin and she received aggressive IV fluid hydration which also improved her kidney function. Within 48 hours, the patient had improved oxygen saturation, resolution of her abdominal pain, and good oral intake marking significant overall clinical progress. She was discharged on home oxygen and few more days of IV vancomycin for bacteremia. IMPACT/DISCUSSION: Tigecycline is a broad-spectrum glycylcycline antimicrobial agent belonging to the tetracycline class of antibiotics. Tetracyclines have been associated with acute pancreatitis in literature, and concerns about tigecycline-induced acute pancreatitis have been raised over the past decade in post marketing surveys, we described one such case above. Using the Naranjo Adverse Drug reaction probability scale, a score of 6 was achieved, indicating that the patient's pancreatitis was probably related to tigecycline. CONCLUSION: We recommend physicians monitor patients for signs and symptoms of pancreatitis including abdominal pain after initiating treatment with tigecycline. There should be a low threshold for ordering lipase levels and abdominal CT imaging where indicated. If the patient has symptoms concerning for acute pancreatitis, consider stopping tigecycline and switching to a different class of antibiotics immediately.
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TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Azithromycin (AZ) is extensively used, with millions of prescriptions written yearly. In 2013 US food and drug administration issued a warning against the pro-arrhythmogenic activity of this drug in the presence of pre-existing cardiac conditions, known QT prolongation or QT-prolonging drug use and electrolyte abnormalities.(1) A recent study collected data on over 12 million patients showing the risk of cardiac events with AZ was rare ~0.03%, and there was no increased risk when compared to amoxicillin.(1,2) Here we report a patient with no known cardiac comorbidities who developed torsades des pointes (TdP) after 2 days of initiating AZ. CASE PRESENTATION: A 77-year-old African American female with a history of acid reflux, type 2 diabetes mellitus, hypertension, hypothyroidism, presented to the emergency room with dyspnea and dry cough for one day. On arrival, patient had a temperature of 99.5F, pulse 115 beats/min, respirations at 32 breaths/min, blood pressure 120/66 and saturating in the 80s on room air, with an unremarkable physical exam. She had leukocytosis at 12.8k, d-dimer 2.15. Computed tomography with angiography ruled out pulmonary embolism but showed bibasilar opacities. She had normal sinus rhythm with a QTc of 393 on ECG at presentation. COVID test was negative;She was empirically treated for community-acquired pneumonia with IV ceftriaxone and IV AZ, with which patient had significant clinical improvement and oxygen requirement. However on day 2 of hospitalization, she developed an episode of generalized tonic-clonic seizure followed by a cardiac arrest secondary to TdP with successful resuscitation in 15 minutes. Magnesium was 1.9, potassium 3.8. In the absence of risk factors like, cardiac disease, arrhythmias, concomitant use of QT prolonging drugs, and significant electrolyte abnormality, this event was attributed to the use of azithromycin. Naranjo adverse drug reaction scale score was 6. While in the ICU, patient was managed with amiodarone, metoprolol, AZ was discontinued. She made marked recovery and was extubated within 3 days, transferred to the floor where no further arrhythmias were noted. She was subsequently discharged to rehab on a short course of amoxicillin-clavulanate, amiodarone, metoprolol, and close cardiology follow-up. DISCUSSION: AZ is a relatively safe drug compared to other macrolides, and reports of cardiac arrhythmias induced solely by this drug with no concomitant risk factors are extremely rare. The evidence from meta-analyses and systematic reviews on the association of AZ with cardiac events are conflicting (3), and further investigations are warranted to assess this association. CONCLUSIONS: This case serves to reiterate the association of potentially fatal arrhythmias induced by a commonly prescribed antibiotic. Although these events are rare, they should be on our radar in clinical practice. REFERENCE #1: Patel H, Calip GS, DiDomenico RJ, Schumock GT, Suda KJ, Lee TA. Comparison of Cardiac Events Associated With Azithromycin vs Amoxicillin. JAMA Network Open. 2020;3(9):e2016864-e2016864. REFERENCE #2: Patel H, DiDomenico RJ, Suda KJ, Schumock GT, Calip GS, Lee TA. Risk of cardiac events with azithromycin-A prediction model. PLoS One. 2020;15(10):e0240379. REFERENCE #3: Almalki ZS, Guo JJ. Cardiovascular events and safety outcomes associated with azithromycin therapy: a meta-analysis of randomized controlled trials. Am Health Drug Benefits. 2014;7(6):318-328. DISCLOSURES: No relevant relationships by Khushdeep Chahal, source=Web Response No relevant relationships by Sangeetha Isaac, source=Web Response No relevant relationships by Sucheta Kundu, source=Web Response No relevant relationships by Ishita Mehra, source=Web Response
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TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Despite exhaustive efforts by the global healthcare to treat COVID-19, the death toll continues to rise. Ivermectin, a known anti-parasitic agent, when re-purposed for treating COVID-19, has demonstrated positive results in several studies. We aim to evaluate the benefit and risk of Ivermectin therapy in COVID-19 patients. METHODS: We conducted a systematic search for full-text manuscripts published from February 1, 2020, to August 15, 2021, that focused on the efficacy and safety of Ivermectin use in COVID-19. Overall mortality and need for intensive care unit (ICU) admission were primary outcomes;secondary outcomes were adverse effects, need for mechanical ventilation, viral clearance, time to viral clearance, need for hospitalization, and length of hospital stay. Random-effects models were used for the quantitative and qualitative analyses. RESULTS: A total of 52 studies (n= 17561) were included in the qualitative analysis and out of these, 44 studies (n=14019) were included in the quantitative analysis. In the qualitative analysis of Ivermectin treatment, a mortality rate of 3.6%, ICU admission rate of 5.4%, mechanical ventilation rate of 3.9%, and adverse event rate of 6.6% were observed. In the overall mortality meta-analysis, odds of death were lower in the Ivermectin-arm compared to the non-Ivermectin arm (OR 0.54, p=0.009). However, in the subgroup analysis of 15 randomized controlled trials, we observed lower odds of mortality in the mild/moderate sub-group (OR 0.31, p=0.06) but without statistical significance. In the severe/critical sub-group, odds were only marginally lowered and were not statistically significant.(OR 0.86, p=0.56). The benefit with Ivermectin was not statistically significant in the meta-analysis of the need for ICU admission (OR 0.48, p=0.17), mechanical ventilation (OR=0.75, p=0.12) and duration of hospitalization (MD -1.80, p= 0.06). The meta-analysis of adverse effects was inconclusive (OR 0.87, p=0.30). Ivermectin, frequently used as adjunctive treatment, was linked with higher odds of achieving viral clearance (OR 3.52, p=0.0002), in a shorter duration (MD -4.12, p=0.02) as well as reduction in the need for hospitalization (OR 0.34, p=0.008). CONCLUSIONS: In the updated quantitative analysis, we found that mortality benefit with Ivermectin treatment is uncertain. Trends of decreased need for ICU admissions and mechanical ventilation, and duration of hospitalization were observed but were not significant. Mostly as an adjuvant treatment, Ivermectin may help accelerate viral clearance as well as reduce the need for hospitalization. Meta-analysis for adverse events suggested that there may be no difference in the adverse event rate with Ivermectin and other treatments, but this cannot be concluded with confidence. The qualitative analysis showed that Ivermectin led to better clinical outcomes in COVID-19 patients and a lower incidence of adverse events. CLINICAL IMPLICATIONS: Well-designed larger observational studies and clinical trials are needed to confirm Ivermectin's mortality benefit in COVID-19 and to further investigate its ideal dosage and timing in the disease course, drug interactions, and possible synergistic drug combinations to achieve maximum benefit. We also need to evaluate the impact of Ivermectin in patients infected with the newly emerging strains and its role in vaccinated patients. Finally, we recommend physicians to exercise caution while prescribing Ivermectin for COVID-19 while we await evidence-based guidelines. DISCLOSURES: No relevant relationships by Vikas Bansal, source=Web Response No relevant relationships by Abhishek Bhurwal, source=Web Response No relevant relationships by Shree Spandana Ghanta, source=Web Response No relevant relationships by Smruti Karale, source=Web Response No relevant relationships by Rahul Kashyap, source=Web Response No relevant relationships by Hira Khan, source=Web Response No relevant relationships by Janaki Makadia, source=Web Response No relevant relationsh ps by Ishita Mehra, source=Web Response No relevant relationships by HEMANT MUTNEJA, source=Web Response No relevant relationships by ROMIL SINGH, source=Web Response No relevant relationships by Muhammad Tayyeb, source=Web Response No relevant relationships by Aysun Tekin, source=Web Response
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INTRODUCTION: Corticosteroid use in COVID 19 patients has been a much debated topic, and there has been no clear evidence so far supporting it as an effective medication to reduce the inflammatory response and improve mortality rates. We aim to review the data on mortality benefits observed with the use of corticosteroids in COVID-19. METHODS: A comprehensive literature search was conducted across the three largest COVID 19 database provided by WHO, CDC, and LitCovid PubMed Database from inception to July 19th, 2020. We included studies that compared the risk of death among patients with and without use of systemic corticosteroids. We then summarized risk estimates into two random-effect metaanalyses;one with randomized controlled trials and another one with observational studies. We analyzed data in Review Manager Software, version 5.2 (Nordic Cochrane Center, Copenhagen, Denmark), to evaluate combined odds ratio (OR) for RCTs and observational studies with respective 95% confidence intervals (CI) using a random-effects model. RESULTS: Out of total 23 articles, 11 studied were included in final meta-analysis. Among these, 3889 patients were treated with corticosteroids and 5954 were not. The metaanalysis of five clinical trials/prospective studies indicated that administration of corticosteroid significantly reduces the mortality compared to the no corticosteroid use (OR 0.52, 95% CI 0.31-0.87, p-value 0.01;I2=76%). However the meta-analysis of six retrospective observational studies/case series showed summed odds ratio of 2.69;95% CI 0.66 to 10.99, p-value 0.17, I2=94%, suggesting increased risk of mortality with use of systemic steroids. CONCLUSIONS: We observed mortality benefits from metaanalysis on available RCTs. On the contrary, a meta-analysis of observational studies suggested a higher risk of death in similar patients;however, the grade of confidence in this subgroup's results is lower due to inherent methodological limitations.
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INTRODUCTION: In the current COVID-19 pandemic, as no proven effective treatment is available, the most efficient strategy is to re-purpose existing antiviral drugs. Remdesivir has demonstrated broad spectrum antiviral activity against an array of RNA virus families. Our systematic review and metaanalysis provides a detailed overview of existing literature on remdesivir in COVID-19 to evaluate the benefits and adverse events of this potential drug. METHODS: A systematic search was conducted for articles published between inception and July 31, 2020 focusing on the use of remdesivir in COVID-19. The primary outcomes were defined as mortality rate and median days to recovery and the secondary outcome was pooled adverse events rate and pooled drug discontinuation rate. Statistical analysis was performed using the Comprehensive Meta-Analysis software package (Bio stat, Englewood, NJ, USA). RESULTS: Six studies were included in our meta-analysis. A total of 1858 patients were included. In patients treated with remdesivir, the median recovery time was 15.84 days (95% CI 11.68-20.00, p<0.0001) and the pooled mortality rate was 9.9% (95% CI 7.0%- 13.8%, p <0.0001). The results of three clinical trials indicated that administration of remdesivir significantly reduces the mortality compared to the placebo (OR 0.70, 95% CI 0.58-0.84, p-value 0.000) as well as shortens the recovery time (OR 1.32;95% CI 1.12 to 1.55, p <.001). However, treatment with remdesivir was associated with adverse effects (62.5%, 95% CI 35.9%- 83.3%, p=0.36) eventually warranting the discontinuation of the drug (16.7%, 95% CI 7.2%- 34.3%, p<0.001). CONCLUSIONS: The results of our meta-analysis suggests that pooled mortality rate of patients of COVID-19 with remdesivir is low. The median recovery time was found to be over two weeks. Our meta-analysis suggests that there may be a favorable risk-benefit profile for remdesivir compared with placebo in severe COVID-19 infection.
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INTRODUCTION: In the current COVID-19 pandemic, no proven effective treatment is available. Critical patients with COVID-19, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation could be a life-saving procedure for COVID-19 patients with extensive pulmonary fibrosis. We aim to highlight this therapeutic surgical management in terms of its indications, efficacy and safety. METHODS: A systematic search was conducted for articles published between inception and July 18th, 2020 focusing on lung transplant as a therapeutic approach for severe lung damage in patients with COVID-19. The primary outcomes defined were efficacy and safety of lung transplant based on the pooled available data along with the peri-operative management RESULTS: Four studies (two case reports and two case series) were included in systematic review. A total of seven patients were included, with a female: male ratio of 0.75: 1. The mean age of the patients was 56.8 years. All of these patients suffered from end stage respiratory failure due to irreversible lung damage even after sero-conversion. Six patients underwent bilateral lung transplant and one patient underwent only right lung transplant. The median (IQR) interval between the diagnosis of COVID-19 and lung transplant surgery was 39.2 (28-56) days. Post-operatively, five patients had no complications and recovered well. One patient had acute rejection of the graft which was managed by steroid pulse therapy while one patient succumbed to death on post-operative day-one. CONCLUSIONS: Lung transplantation could be considered as a treatment option for end-stage COVID-19 patients with extensive pulmonary fibrosis leading to respiratory failure. It could be the potential last resort in sero-converted patients without multiple organ dysfunction.
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INTRODUCTION: In this systematic review, we assessed the clinical outcomes, benefits, and adverse effects associated with tocilizumab use in hospitalized COVID-19 patients. We aimed to seek insight on the role of tocilizumab in COVID-19 associated hospitalization. METHODS: A literature search was conducted using the electronic database engines WHO, PubMed, and Google Scholar from December 1st 2019 to June 22nd 2020. The inclusion criteria of the primary studies for our review included: 1) RT-PCR SARS-CoV-2 positive patients/ Confirmed COVID-19 patients, 2) Age>/= 18, 3) Need for hospitalization-, 4) Use of tocilizumab for the treatment of COVID-19. The search strategy retrieved 383 studies in total, of which only 37 qualified for inclusion with a total of 677 patients. The primary outcomes analyzed in this study were patients' ?clinical improvement/recovery or stabilization?, ?clinical deterioration but alive at the end of the study? after tocilizumab administration and mortality rate. The secondary outcomes included length of hospital stay (LOS), radiological improvement, and mean change in C - reactive protein (CRP) levels before and after tocilizumab administration, mean change in ferritin levels before and after tocilizumab administration and adverse events. RESULTS: After the administration of 1 or more doses of tocilizumab, clinical improvement/recovery or stabilization was noted in 462 (68.2%) out of 677 patients, whereas 31 (4.6 %) out of 677 patients clinically deteriorated but remained alive at the end of the study. A total of 103 (15.2%) patients died. Radiological improvement was noted in 108 (69.7%) out of 155 patients, the average LOS reported ranged from 5 to 25 days, mean change in CRP levels before and after tocilizumab administration reported ranged from 5.9 mg/L to 2400 mg/L, and the mean decrease in ferritin levels before and after tocilizumab administration reported ranged from 62.08 ng/ml to 51156 ng/ml. Finally, 97 (14.3 %) out of 677 patients experienced one or more adverse events. CONCLUSIONS: In a literature review of 37 studies, Tocilizumab as a management of critically ill hospitalized patients with COVID-19, this drug was found to be associated with improvement in both survival and radiological findings. A minority of patients were reported to have adverse events.