Correlation Between the Suitability of Empirical and Definitive Therapies According to Culture Results with the Clinical Outcomes of Patients with Bacteremia Due to Carbapenem- Resistant Acinetobacter baumannii (CRAB) at Dr. Soetomo Tertiary Referral Hospital

Carbapenem administration is an important therapy for nosocomial infections due to MDRO, especially Acinetobacter baumannii. The global increase in carbapenem-resistant A. baumannii (CRAB) that causes this pathogen has significantly threatened public health due to the lack of adequate treatment options due to the very few currently available antimicrobial agents that actively fight CRAB. Antimicrobial resistance is a major negative impact of inappropriate antimicrobial prescribing. Ineffective empiric treatment (initial antibiotic regimen not sensitive to identified pathogens based on in vitro sensitivity test results) is associated with a higher rate of deaths compared to effective empiric treatment. In this study, we analyzed the correlation between the suitability of empiric and definitive antibiotics and the clinical outcomes of patients with bacteremia due to CRAB treated in the inpatient ward of Dr. Soetomo Tertiary Referral Hospital, Surabaya. There were 227 isolates of bacteremia due to CRAB, consisting of 156 carbapenem-resistant A. baumanni and 71 carbapenem-sensitive A. baumannii. There were 88 isolates that met the inclusion and exclusion criteria, and all of them were resistant to ceftriaxone, cefepime, and ciprofloxacin. A total of 29.5% of the isolates were sensitive to cotrimoxazole, 3.4% of the isolates were sensitive to tigecycline, and 2.3% of the isolates were sensitive to amikacin, levofloxacin, and cefoperazone sulbactam. Adequate empirical antibiotics and definitive antibiotics (sensitive based on culture sensitivity test) amounted to 12.5% and 27.3%, respectively. There is no significant correlation between the suitability of empiric and definitive therapies with the patients' clinical outcomes (death and length of stay).Copyright © 2022 Phcogj.Com.

Cytokine elimination in suspected COVID-19 perymyocarditis

Background: Only recently studies have been able to demonstrate the safety and efficacy of purification therapies in inflammatory diseases. Here we present the management of a young (21y) male patient in severe cardiogenic shock due to COVID-19 perymyocarditis admitted to the ICU at Bolzano Central Hospital. November 30th 2020 the patient developed high fever (>40 C) and diarrhea. After unsuccessfully being treated orally with a macrolide he was admitted to a peripheral hospital the 4th of December. The day after he deteriorated, required transfer to the ICU, endotracheal intubation and pharmacological cardiovascular support (Norepinephrine, Levosimendan). Antimicrobial treatment was started with piperacillin/tazobactam, linezolid and metronidazole. Despite multiple radiological and microbiological diagnostic attempts the origin of this severe septic shock remained unclear. December 6th the patient was transferred to Bolzano Central Hospital for VA-ECMO evaluation. Method(s): The transesophageal echocardiography revealed 15-20% of EF, lactate (5,2 mmol/l), cardiac enzymes (TropT 1400 mcg/l) and inflammatory parameters (PCT 35 ng/ml, IL-6 685 pg/ml) were elevated. We performed cardiac monitoring via Swan-Ganz catheter. The cardiac index was 1,6 l/min/m2. The peak dosage for Norepinephrine reached 7,5mg/h (1,47 mcg/kg/min). At Bolzano ICU we facilitate the pharmacological therapy with milrinone, vasopressin and low dose epinephrine. Furthermore, we impost continuous hemodiafiltration with CytoSorb filter. Result(s): Only hours after the start of filtration therapy the patient improved and we were able to gradually reduce catecholamine therapy, lactate values decreased. A VA-ECMO implantation was no more necessary. December 10th, we saw a stable patient without ventilatory or cardiovascular support, at echocardiography we revealed a normal EF. Conclusion(s): Clinically we saw a young patient in severe septic/cardiogenic shock due to perimyocarditis. Yet diagnostic attempts (CT-scan, multiple blood/urinary/liquor cultures) remained negative. Despite multiple negative PCR tests for SARS-CoV2 infection we performed specific immunoglobulin analysis and received a positive result for IgM. We therefore conclude on a COVID-19 associated perymyocarditis. Furthermore, this case illustrates the potential benefit of cytokine filtration and elimination in COVID-19 patients with altered IL6 levels.

Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

Acute exantematic pustulosis generalized by meropenem, differential diagnosis with COVID

Case report We present the case of a 63-year- old man with two consecutive admissions, due to COVID19 infection and subsequent bacterial superinfection. Three days after the second admission (04/28), and 43 days from the beginning of the infection an assessment by dermatology and allergology is then requested. The patient had generalized erythematous maculopapular rash in the trunk, back, groin and limbs. On the left side and back, pustular lesions not focused on follicles were also added, with a fever of 37.7degreeC. There were no oral and genital lesions. No psoriasis. The drugs used during the present and previous admissions were reviewed. Previous admission (04/04-22/ 20): Linezolid, ciprofloxacin, meropenem 04/13-22, piperacillin/tazobactam, hydroxychloroquine, azithromycin, ceftriaxone. Upon discharge amoxicillin/acid clavulanic. Present admission (04/25) Cutaneous reaction 04/28. 04/25: meropenem, paracetamol, enoxaparin, insulin, omeprazole, venlafaxine. 04/26: Darbepoetin, furosemide, mycophenolate in single dose. 04/27: Linezolid, macrogol, Clopidogrel, Magnesium, Calcitriol. Medical records: DM type 2, liver transplantation due to HCV cirrhosis, HCV recurrence, uninodular hepatocarcinoma, advanced CKD, secondary hyperparathyroidism, multiple neurological antecedents. We performed a detailed study. We hypothesized with a pharmagological/ drug reaction with several drugs possibly involved and our main suspicion was an allergic reaction to beta-lactams. Biopsy: Subcorneal pustules, basal spongiosis and presence in the superficial dermis of edema and an inflammatory infiltrate with abundant neutrophils. No fungi. Findings compatible with clinical diagnosis of generalized acute exanthematic pustulosis (PEGA). Immunohistochemical study Covid19. (Jimenez Diaz Foundation) Finely granular positivity in endothelium and more coarse in sweaty epithelium. Neutrophilic superficial inflammatory component with presumably spure staining. ACe-2 (positive external control) is not detected. The patient presents a EuroSCAR score of 9, sum of the clinic and the pathological anatomy, and therefore defined diagnosis. Clinical diagnosis: PEGA secondary to meropenem. Conclusion(s): We present the case of a PEGA by meropenem, not very often described in the literature. We highlight the importance of differential diagnosis with viral infections. Skin tests, especially epicutaneous tests, are key to the diagnosis. (Figure Presented).

Study of Prescription Pattern of Covid-19 Intensive Care Unit Patients in a Tertiary Care Hospital

COVID- 19 was the most challenging public health problem worldwide for better part of 2 years (2019 - 2021). Although several of the medication have not demonstrated promising benefits in the majority of research, they are nonetheless utilized. The purpose of this study was to compare and contrast the hospital pharmaceutical care of COVID-19 patients by sex, age group, and with regards to oxygen consumption classifying and grouping them with comorbidities seen and auxiliary medication given . Hospital based retrospective observational study was conducted among 123 patients with antigen positive Reverse Transcriptase Polymerase Chain Reaction confirmed COVID- 19 infection admitted in the ICU for 24 hours prior. As the age increased the chance for ICU admission also increased. The most affected age group was above 50 years of age. The total number of patients requiring oxygen was 100% in COVID- 19 ICU patients. Some of the most common comorbidities were heart disease (18%) followed by Diabetes Mellitus (15%) and Hypertension (15 %). Only 48 % of patients received antivirals. Remdesivir which was the mainstay antiviral was given (41%). Amoxicillin and clavulanate combination (Augmentin 625 mg) was the most commonly prescribed antibiotic (27%).The antipyretic of choice was paracetamol which was given to 100% of patients. Almost all patients (78%) were given enoxaparin sodium as the anticoagulant of choice. Regardless of equivocal results, multivitamins and supplements were recommended to all patients. All prescription guidelines as given by ICMR for COVID- 19 ICU patients were followed with the exception of the extensive antimicrobial use.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Isolated tracheobronchial mucormycosis: Report of a case and systematic review of literature

Background: Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and perform a systematic review of the literature. Case description and systematic review: A 45-year-old gentleman with poorly controlled diabetes mellitus presented with cough, streaky haemoptysis, and hoarseness of voice 2 weeks after mild COVID-19 illness. Computed tomography and flexible bronchoscopy suggested the presence of a tracheal mass, which was spontaneously expectorated. Histopathological examination of the mass confirmed invasive ITBM. The patient had complete clinical and radiological resolution with glycaemic control, posaconazole, and inhaled amphotericin B (8 weeks). Our systematic review of the literature identified 25 additional cases of isolated airway invasive mucormycosis. The median age of the 26 subjects (58.3% men) was 46 years. Diabetes mellitus (79.2%) was the most common risk factor. Uncommon conditions such as anastomosis site mucormycosis (in two lung transplant recipients), post-viral illness (post-COVID-19 [n = 3], and influenza [n = 1]), and post-intubation mucormycosis (n = 1) were noted in a few. Three patients died before treatment initiation. Systemic antifungals were used in most patients (commonly amphotericin B). Inhalation (5/26;19.2%) or bronchoscopic instillation (1/26;3.8%) of amphotericin B and surgery (6/26;23.1%) were performed in some patients. The case-fatality rate was 50%, primarily attributed to massive haemoptysis. Conclusion: Isolated tracheobronchial mucormycosis is a rare disease. Bronchoscopy helps in early diagnosis. Management with antifungals and control of risk factors is required since surgery may not be feasible. © 2022 Wiley-VCH GmbH.

Cardiac Magnetic Resonance Imaging for the Diagnosis of Infective Endocarditis in the COVID-19 Era

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.

Community-acquired Methicillin-resistant Staphylococcus aureus Pneumonia and Parapneumonic Effusion in a Male Patient with Diabetes: A Case Report

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a primary health concern. They are commonly differentiated as hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) and community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, based on their epidemiology, susceptibility findings, and molecular typing patterns. Therefore, appropriate contact precautions and isolation measures should be implemented. CA-MRSA mostly causes skin and soft-tissue infections, but the probability and incidence of it causing sepsis and invasive infections have increased dramatically in recent years. In this study, we report a case of CA-MRSA pneumonia with pan-pneumonic effusion in a 59-year-old male diabetic patient with preexisting comorbidities such as diabetic ketoacidosis and non-ST elevated myocardial infarction. The early reporting of the organism's identity and its antimicrobial susceptibility, as well as timely initiation of antibiotic therapy, aided in the successful management and cure of the patient.

A TALE OF A DRUG THAT KILLED A BUG BUT CAUSED PNEUMONIA: A CASE REPORT OF DAPTOMYCIN-INDUCED ACUTE EOSINOPHILIC PNEUMONIA

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

Mucormycosis, Acute Necrotising Pancreatitis and Haemorrhagic Stroke Occuring Simultaneously in an Immunocompetent Male: The Unwarned Apocalypse

Mucormycosis or zygomycosis is a life threatening invasive fungal infection, usually seen in patients with alteration of their immune system. It is a lethal and an aggressive fungal infection caused by the fungi of the order Mucorales. The angioinvasive property of mucormycosis can lead to fatal complications such as intracranial bleed. Acute pancreatitis refers to inflammation of the pancreas which presents mainly as acute pain in the abdomen and is a potentially fatal condition. The association of mucormycosis with acute pancreatitis is rare but dangerous. This case report highlights a case of 32-year-old male patient, with no co-morbidities, who was admitted to an rural central Indian hospital with four days of abdominal pain and two days of headache. Patient appeared to be in good health prior to this event. He was ultimately diagnosed with mucormycosis of paranasal sinus with acute pancreatitis. The patient was treated with intravenous antifungals, antibiotics and fluid therapy along with other supportive measures. Patient later developed intracranial bleed five days after admission, and ultimately succumbed on day seven of admission. After an extensive review of literature it was found that this is the first article to report mucormycosis, acute pancreatitis and intracranial bleed all occurring at once in an immunocompetent male.

STUDYING THE ETIOLOGY OF COMMUNITY-ACQUIRED PNEUMONIA IN CHILDREN TREATED IN THE HOSPITAL

The study determined the etiological structure and sensitivity to antibacterial agents of pathogens of uncomplicated and complicated forms of pneumonia in children treated in a multidisciplinary hospital. According to the study, that timely bacteriological diagnosis in the treatment of pneumonia in childhood with an adequate selection of effective antibacterial agents helps reduce hospitalizations and the development of complicated forms of pneumonia.

SWEET SYNDROME IN ACUTE MYELOGENOUS LEUKEMIA- A CASE REPORT

CASE: Patient is a 63 y/o F with PMH of relapsed AML on treatment with Gilteritinib, Meniere's Disease, asthma, GERD, PRA positive, CKD Stage 3. She was on cycle 1 day + 20 of Gilteritinib when she presented with a neutropenic fever of 101.9. She reported congestion and headache. She was pan cultured and started on empiric Cefepime. Her blood cultures, COVID test and CXR were all negative for sources of infection. Eventually, Cefepime was stopped, and she was transited to PO Cefdinir and Cipro but redeveloped fevers and a maculopapular rash. Repeat pan-cultures were negative. Antibiotics were broadened to Merrem, Linezolid and Cresemba and her fevers improved. However, the rash continued to worsen. There was concern that nodular rash was secondary to infection or possible drug reaction from her antibiotics. Her rash showed no improvement with Benadryl or withholding drugs. She underwent skin punch biopsy before discharge. Biopsy showed florid superficial inflammation with benign ulcer that was highly suggestive of Sweet Syndrome given history of AML. IMPACT/DISCUSSION: Sweet syndrome (SS), or acute febrile neutrophilic dermatosis is a rare inflammatory condition characterized by painful cutaneous nodules and neutrophilic infiltrate in the dermis, in the absence of vasculitis. This syndrome is associated with malignancies with AML and MDS being the most reported. Malignancy associated Sweet Syndrome accounts for 15-20% of cases of SS. The atypical production of both pro-inflammatory cytokines (IL - 6, TNF - alpha) and signaling molecules demonstrated in AML is suspected to affect neutrophil function leasing to dermal clumping of the mature neutrophils. In our patient the fever presented prior to the rash with sudden onset of nodular as it has been commonly reported in literature review. Glucocorticoids, either topical or systemic, together with antibiotics and wound care, represent the mainstays of SS therapy. The rash heals without scarring if no ulcerations are present. The signs and symptoms of Sweet syndrome can mimic infection and be treated inaccurately, thus, it is important to make a correct diagnosis. Our patient's tissue cultures were negative for microorganisms. She was started on glucocorticoid with good response in regards to her rash but did have some scars and hyperpigmentation. Unfortunately due to her aggressive AML and complications patient elected to go to Hospice. CONCLUSION: When SS is established, the physician should keep a high index of suspicion to search underlying malignancies. Sweet Syndrome generally responds promptly to treatment with glucocorticoid.

DOUBLE TROUBLE: COVID-19 PNEUMONIA CONCURRENT WITH COVID-19 ASSOCIATED PULMONARY ASPERGILLOSIS (CAPA)

CASE: A 52-year-old male with a past medical history of asthma and uncontrolled OSA presented to the ED ten days after diagnosis of COVID-19 with worsening dyspnea. He had a history of fluticasone propionate and fluticasone salmeterol use for asthma exacerbations. He endorsed cough, fever, chills, and diarrhea, and denied chest pain, leg edema, and anosmia.Vitals showed oxygen saturation of 65%. CBC demonstrated leukopenia consistent with COVID- 19 infection. Blood labs showed hyperglycemia (blood sugar 182 mg/dL, hemoglobin A1c 9.6%). Bilateral crackles were noted on exam. He was placed on high-flow nasal cannula (HFNC) immediately due to critical hypoxemia. CT PE was negative;CXR revealed bilateral opacities consistent with COVID-19 pneumonia. He started on dexamethasone and remdesivir and was admitted to the MICU for acute hypoxemic respiratory failure. Notably, the patient had no known diagnosis of diabetes mellitus and was started on sliding scale insulin and Lantus. Barcitinib was added in the MICU in addition to linezolid and cefepime for fear of bacterial superinfection but were discontinued after receiving negative cultures. He was transferred out of the MICU four days later after successful weaning of oxygen but soon returned due to worsening oxygen needs. New leukocytosis prompted a repeat respiratory culture, which grew mold on the preliminary read. Voriconazole was initiated due to concern for Aspergillus infection and was continued with confirmation on the final read. Repeat CT showed left pneumomediastinum, right apical pneumothorax, and worsening bilateral opacities. Despite ongoing treatment, the patient required NC at rest and HFNC with minimal exertion. He was discharged home with HFNC. IMPACT/DISCUSSION: CAPA is a result of opportunistic fungal infection, causing devastating disease in the immunocompromised. A crucial risk factor is the use of high-dose corticosteroids for a prolonged period. The diagnosis of CAPA is based on a combination of imaging, microbiology, and clinical presentation. Peripheral nodules, air crescent, reverse halo sign, nodular consolidation, ground-glass opacities, crazy paving pattern, pleural effusion, and pulmonary cysts have been reported among CAPA patients. A fungal culture and galactomannan test from respiratory specimens can aid in early diagnosis. The usual presenting symptoms of CAPA include refractory fever, pleuritic chest pain, or dyspnea. Voriconazole is a first-line anti-Aspergillus agent. CONCLUSION: Clinical presentation of CAPA is often subtle but associated with high morbidity and mortality. Multiple reports add support to our observation that CAPA can be a result of worsening COVID-19 pneumonia. Early diagnosis and treatment are vital to prevent worse clinical outcomes. Physicians should demonstrate a heightened awareness of the risk of developing CAPA in critically ill COVID-19 patients. Clinicians should exercise low thresholds to identify and treat CAPA, especially in patients on high-dose steroids long-term.

Deep Vein Thrombosis, Septic Pulmonary Emboli and Methicillin-Resistant Staphylococcal Aureus Bacteremia Complicated by a Furuncle in a Child

Staphylococcal aureus infection in children is a major public health problem globally. It causes a varied spectrum of clinical disease including bacteremia, endocarditis, skin and soft tissue infection, pleuro-pulmaonry and osteo-articular infection. Deep vein thrombosis (DVT) is a known complication of staphylococcal infection. We report a case series which included, 10-year old boy developed DVT, septic pulmonary emboli and Methicillin-resistant Staphylococcal aureus (MRSA) bacteremia following a furuculosis and 13 year old girl with thrombosis of internal and external jugular vein, cavernous sinus with pulmonary emboli and MRA bacteremia. Both patients are previously healthy showed complete recovery after aggressive appropriate antibiotics, anticoagulants and supportive care. The high index of suspicion of DVT in MRSA infection is needed, prompt diagnosis and aggressive appropriate therapies improve the outcomes and minimize the complications.

Haematological alterations in hospitalized patients with COVID-19: Drugs involved in its aetiology

Objective: To explore the role of the drugs used to treat COVID-19 in the haematological alterations identified in patients hospitalized due to SARS-CoV-2 infection. Material and/or methods: Post-authorization observational study of 245 patients with confirmed SARS-CoV-2 (COVID-19) infection hospitalized and treated between March and April 2020 in five hospital centres in the Cantabria region. To be included in this study, complete information on the treatment used and periodic haematological examinations must be available. The data was taken from the COVID-19 Registry (NCT04347278). Results: One hundred forty-five of 245 patients (59.2%) presented haematological alterations during the acute process of infection. Leukopenia-lymphopenia appeared in 64% of the cases with alterations in the blood count and 42% presented thrombopenia. In 80% of the cases, this alteration resolved as soon as the clinical evolution of the patient improved. The following drugs were used to treat this infection: hydroxychloroquine (97.9%), lopinavir-ritonavir (82%), interferon beta-1b (7.7%), tocilizumab (20.4%) and anakinra (3,3%). The additional treatments used were enoxaparin (87.3%), methylprednisolone (23.6%), as well as antibiotics, antifungals and antivirals in patients with coinfections. A compatible temporal relationship was identified between the administration of tocilizumab and the appearance of leukopenia or worsening of pre-existing leukopenia in 40% of patients, with leukocyte recovery being observed 72 h after discontinuation of the drug. No temporal relationship was observed when other drugs were used. Regarding thrombopenia, the use of linezolid was causally involved in 8% of the patients, showing resolution in 60% of the cases when the drug was discontinued. Conclusions: Patients infected by COVID-19 can develop leukopenia-lymphopenia and thrombopenia in relation to infection by the virus itself. Tocilizumab in case of leukocyte involvement and linezolid in case of platelet decline have been shown to play a role in these haematological alterations.

A case of toxic epidermal necrolysis in a COVID-19 patient

Background: We report a severe hypersensitivity reaction due to warfarin in a COVID19 patient with sepsis. Case Report: An 86-year-old man was admitted for COVID19 pneumonia. He was vaccinated with 2 ComirNaty doses. He was affected by hypertension and CKD in emodialysis. At the admission he presented fever and tachypnea, the laboratory tests showed a septic state. We started administration of empiric therapy with piperacillina/tazobactam, it was replaced with meropenem and linezolid on the 29th day. After 10 days linezolid was stopped for thrombocitopenia. On the 14th day we prescribed warfarin for tromboembolic risk prevention when paroxysmal atrial fibrillation occurred . At the fifth week there was a clinic and laboratory worsening so we started target antibiotic therapy with cefiderocol and colistin due to positive blood cultures for A. Baumanii XDR. On the 24th day an inguinal erytema with blister-like lesion occurred and involved progressively face, neck, limbs, trunk and abdomen with extensive skin sloughing and crusted lesions appeared in the perioral and perinasal mucosa. Nikolsky sign was negative. Skin biopsy showed signs of inflammatory reaction. Warfarin was stopped and 1mg/kg methylprednisone was started with slow and progressive benefit. Conclusions: The patient has developed a warfarin linked hypersensitivity reaction with clinical features similar to toxic epidermal necrolysis. We assume that it was a borderline condition of hypersensitivity to warfarin in a patient with hyperactivation of immune system due to COVID19 and sepsis.

Effectiveness and safety of dalbavancin off label treatment during pandemic

Background: Dalbavancin is a lipoglycopeptide antibiotic approved for treatment of acute bacterial skin infection by GRAM +, also used for his long half-life in bone infection. Case Report: A 72 years old patient was admitted to hospital with low-grade fever for 40 days and back pain after two hospitalization for COVID19 infection and ischemic stroke. Blood examinations showed: elevated white blood cells count, increased inflammatory markers and anemia. CT showed bilateral pleural effusion, MRI configured vertebral alteration (D7-D9) suggesting infectious spondylodiscitis, blood and pleural liquid culture evidenced Staphylococcus Aureus MSSA. Levoxacin 500mg2/day and linezolid 600mg2/day IV were started with clinical improvement. Following the patient request, he was discharged with oral Linezolid. Two weeks later he showed worsening back pain and high inflammatory index. Levoxacin 500mg and Rifampicin 600mg were administered 2/day, soon Rifampicin substituted with Minocycline 100mg/day for side effect onset. After 4 week, MRI confirmed worsening of inflammatory state. Based on proven efficacy, Dalbavancin 1500mg/day IV on day 1 and 8 was started, with Minocycline for 24 week, with significant improvement in followup MRI;pleural effusion and inflammatory markers decreased. Conclusions: This case shows high efficacy of dalbavancin in spondylodiscitis pyogenic infection and pleural empyema, avoiding complications and high cost of long-term hospitalization during pandemic. In particular condition the use off label of dalbavancin is a safe and cost effective treatment.

Acute intracranial bleed symptoms mimic by lactic acidodis linezolid induced

Introduction: Rarely, lactic acidosis can be a life-threatening medication side effect. Hence, determining the etiology of lactic acidosis early in patients is necessary to choose the correct therapeutic intervention. Although lactic acidosis as an adverse drug reaction of linezolid is a well-recognized and documented clinical entity. Case Report: A 90-years-old woman was hospitalized for Sars- CoV-2 related pneumonia, due to an increase of CRP, WBC count and appearance of new opacities on chest CT, it has been decided to start an atimicrobial therapy with Linezolid, suspecting an MRSA superinfection. After six doses she presented an episode of consciusness alteration, lethargy and allucinations.The head CT any bleeding or mass effect has been demonstrate, but blood gas analysis showed a significant lactic acid increase and an important HOC3- reduction. After the suspencion of Linezolid lactate rapidly decrease. Conclusions: Several publications demonstrate that linezolid induces lactic acidosis by disrupting crucial mitochondrial functions, rarely with a rapid onset.It is important that internist are aware that linezolid can cause lactic acidosis not only after a long threatment period but also after few somministration, and that often it may mimic a common disease like cerebrovascular accident. In conclusion, linezolid should be suspected in the differential diagnosis if lactic acidosis exists with an uncommon clinical picture.

TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II-III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis.

BACKGROUND: Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9-24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. METHODS: TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. DISCUSSION: TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment. TRIAL REGISTRATION: Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.

Analysis of efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis.

OBJECTIVES: The study aimed to explore the efficacy and safety of linezolid-based chemotherapeutic regimens for patients with postoperative multidrug-resistant spinal tuberculosis. METHODS: The randomized controlled study included 50 Mycobacterium tuberculosis culture or pathological-confirmed multidrug resistant tuberculosis patients who received spinal surgery from January 2018 to February 2020. Twenty-five patients were assigned to the control group and the study group, respectively. Random number method was used for patient allocation and they were treated with levofloxacin, pyrazinamide, thioisonicotinamide enteric-coated tablet, amikacin sulfate injection, and sodium p-amino salicylate injection, accompanied by linezolid or not. RESULTS: The overall effective rate of the study group was higher than that of the control group (88.00% vs 64.00%, P<0.05). The severity of pain at 3 and 6 months postoperatively was lower in the study group than that in the control group (P<0.05). Postoperatively, the study group had higher bone graft fusion rate, shorter mean bone graft fusion time, and higher paraspinal cyst absorption rate than the control group (P<0.05). Postoperatively, the study group had lower levels of PCT, ESR, and CRP than the control group (P <0.05). All patients had normal hepatic and renal function, and no statistical difference of adverse effects between 2 groups were found. CONCLUSIONS: Linezolid-based chemotherapeutic regimens can effectively treat patients with postoperative multidrug-resistant spinal tuberculosis but have higher rates of adverse reactions.