Molecular detection of plasmid-mediated quinolone resistance genes among clinical isolates of Klebsiella pneumoniae during Covid-19 pandemic

Plasmid-mediated quinolone resistance (PMQR) genes confer low resistance to Fluoroquinolones (FQs). This study aims to detect five PMQR genes among FQs-resistant Klebsiella pneumoniae isolated from various clinical specimens. Out of 120 K. pneumoniae isolates, 68 FQs-resistance K. pneumoniae were included in a molecular study. Standard microbiological tests were used for identification and antimicrobial susceptibility. For the detection of PMQR genes, conventional polymerase chain reaction was used. A molecular study revealed that (73.5%) of samples harbored PMQR genes, and among them, 58% were co-carriages of PMQR gene variants. Aac (6')-Ib-cr gene was predominant (47.1%) among samples, and qepA had the lowest percentage (11.8%), qnr genes were (32.4%) (29.4%) (20.6%) qnrS, qnrB, and qnrA respectively. Overall, high percentages of PMQR genes were detected, and almost all of samples were phenotypically resistant to ciprofloxacin. As well, there was a significant statistical relationship between phenotypically ESBL-producers and qnrB and qepA genes.Copyright © Abdulkareem MM et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Clinical profile of hospitalized spanish patients allergic to antibiotics

Background: Only between 1% and 10% of patients labelled of penicillin allergy are allergic. The negative events associated with this condition include risk of antimicrobial treatment failure, antimicrobial resistance, side-effects from use of a broader spectrum antibiotic, and increased healthcare costs. Our objective was to know the clinical profile of hospitalized allergic patients to estimate the future need for an allergy study. Method(s): We collected data from 15 Spanish hospitals about hospitalized patients labelled as allergic to antibiotics in February 2020 and October 2020 (one-month sample) outside the peak of the Covid-19 pandemic. Result(s): 620 patients were collected, 59% women. Mean age 70.6 years (3-103). 416 patients were labelled as allergic to beta-lactams (105 aminopenicillins, 18 cephalosporins, 4 carbapenems). 41 to aminoglycosides, 26 to macrolides, 55 to quinolones and 4 to glycopeptides. The causes of hospitalization were: Respiratory infection 221 (35.6%), abdominal infection 95 (15.3%), orthopaedic surgery 58 (9.4%), urine infections 57 (9.2%), skin infections 51 (8.2%), gynaecological/ obstetric pathology 21 (3.4%) Only 163 patients (26%) had previously received a clinical allergy work-up. 70 confirmed allergy to antibiotics, however the rest 93 (74%) were not delabelled. Patients received alone or combined alternative antibiotics: 79 glycopeptides, 49 aminoglycosides, 28 macrolides, 254 quinolones, 205 beta-lactams (102 cephalosporins, 41 carbapenems and 57 aminopenicillins). 74 patients (12%) would need an immediate allergic study in order to receive first-line antibiotic, but it was only really done in 38 (6.1%). The studied antibiotics were: 15 carbapenems, 10 ceftriaxone, and others not specified. Of the 416 patients labeled as allergic to beta-lactams, 150 (36%) received beta-lactam antibiotics despite the warning in their clinical reports. Conclusion(s): Allergy to beta-lactams remains the most frequent diagnosis of allergy to antibiotics and implies treatment with second-line antibiotics. Respiratory, trauma, digestive and urinary infections are the main causes of the use of antibiotics in hospitalized patients. The underlying diseases could be a risk factor for antibiotic requirements. Some patients received beta-Lactams despite the alert with a potential risk of an allergic reaction and legal implications. The promptly allergological study would imply an improvement in the use of more specific antibiotics with a good level of security.

TULAREMIA PRESENTING AS LARGE GI ULCERATION AND HEMORRHAGE

SESSION TITLE: Critical Care Infections SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Francisella tularensis is a zoonotic disease by an aerobic, gram negative coccobacillus. It is transmitted by exposure to infected animal or vectors in individuals who landscape or camp. Common symptoms are fever, chills, anorexia, and headache. Abdominal tularemia can present with abdominal pain, emesis, diarrhea, and rarely intestinal ulceration and hemorrhage. It is treated with aminoglycosides, fluoroquinolones and tetracycline. CASE PRESENTATION: 38-year-old male presented with fever, cough, anorexia, and black stool for 5 days. Patient worked as a landscaper. He has no pets, travel history or sick contacts. He does not take any medications at home. Physical exam was significant for sinus tachycardia and rhonchi of right upper lobe. Significant labs include WBC of 9.8 with 41% bands, hemoglobin 15.5, sodium 125, procalcitonin 27.3, and lactic acid 1.8. COVID-19, MRSA, Legionella and Pneumococcal urine antigen were negative. CTA chest revealed mass-like opacity in right upper lobe with multiple bilateral pulmonary nodules. Lower respiratory culture showed Candida albicans. Patient was empirically started on ceftriaxone and azithromycin. He was transferred to intensive care for worsening respiratory status and was placed on non-invasive ventilation on hospital day 1. Antibiotics were broadened to ceftaroline and levofloxacin due to suspicion of tularemia. Amphotericin B was added. Labs for Histoplasma, Blastomyces, TB, Leptospira, and HIV were negative. Patient then suffered a cardiac arrest on hospital day 2 after having large brown secretions pouring from his mouth. Cardiopulmonary resuscitation was initiated and patient was intubated and started on vasopressors with return of spontaneous circulation. Massive blood transfusion protocol was initiated. Emergent bedside upper endoscopy showed large blood clot adherent to duodenal ulcer. Interventional radiology planned on performing gastric duodenal artery embolization. However, patient suffered two more cardiac arrest with resuscitation efforts terminated per family request. Karius Digital Culture later was positive for Francisella tularensis. Autopsy revealed diffuse alveolar hemorrhage, hilar lymphadenopathy, and perforated duodenal ulceration with large adherent clot. DISCUSSION: Gastrointestinal tularemia is rare and usually from drinking contaminated water or oral inoculation of bacteria. Intestinal tract involvement can present with mesenteric lymphadenopathy and ulcerative lesions resulting in gastrointestinal bleeding with case fatality rate of 50%. Even though this is noted in the literature, to our knowledge no case reports have been published. CONCLUSIONS: Careful history taking and early identification of risk factors are important when severe tularemia infection is suspected such as in individuals with extensive outdoor activities. Treatment should be empirically initiated in high risk patients. Reference #1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585636/ Reference #2: https://casereports.bmj.com/content/2017/bcr-2017-22125. Reference #3: Altman GB, Wachs JE. Tularemia: A pathogen in nature and a biological weapon. Aaohn Journal. 2002 Aug;50(8):373-9. DISCLOSURES: No relevant relationships by Maria Haider Baig

A CASE OF BORDETELLA BRONCHISEPTICA AND PNEUMOCYSTIS JIROVECI PNEUMONIA IN A YOUNG PATIENT

SESSION TITLE: Procedures in Chest Infections Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumonia is a common condition that is seen in hospitals. Pneumocystis Jirovecii is an opportunist fungal pathogen. Bordetella bronchiseptica is a gram negative bacteria that causes infectious bronchitis in dogs and other animals, but rarely infects humans. CASE PRESENTATION: Patient is a 34 year old African American female with history of sickle cell trait, reported Lupus (not on treatment), asthma, COVID pneumonia who was admitted for worsening shortness of breath & productive cough with yellow sputum. She was previously hospitalized and discharged after being treated for Community-Acquired Pneumonia. In the ER, she was febrile, tachycardic, tachypneic, & hypoxic requiring BiPAP. CXR obtained showed findings concerning for multifocal pneumonia. Chest CT Angiogram was negative for PE. Patient was started on Vancomycin & Meropenem for treatment of her pneumonia. Blood cultures, Legionella, Strep pneumoniae, Aspergillus, Beta-D-glucan, Sputum culture, & MRSA screen were ordered for further evaluation of her infection. ANA screen reflex panel, lupus anticoagulant, anticardiolipin antibodies, beta-2 glycoprotein antibodies were also ordered given patient's reported history of SLE and the concern for SLE pneumonitis: ANA & Sjogren's Anti-SSA were positive;otherwise, autoimmune workup was unremarkable. During hospitalization, patient was eventually weaned down to nasal cannula and antibiotic was de-escalated to levaquin. However, sputum culture eventually grew Bordetella Bronchiseptica that was resistant to Levaquin so antibiotic regimen was switched to Doxycycline. In addition, Beta-D-glucan was noted to be elevated. Bronchoscopy was done for further evaluation;multiple transbronchial biopsies were positive Pneumocystis Jirovecii. Patient was then initiated on Bactrim for treatment of PJP Pneumonia along with a steroid taper. Patient was tested for HIV and it was negative. DISCUSSION: In this case, patient was found to have two rare pathogens, that are more common in immunocompromised patients such as those with HIV/AIDS, on high-dose corticosteroids or malignancy. This patient had a unconfirmed diagnosis of SLE and past COVID Pneumonia. Patient had Bordetella bronchiseptica pneumonia that is frequently isolated in the respiratory tract of animals but can cause severe respiratory infection in humans. This microorganism can cause upper respiratory tract infections, pneumonitis, endocarditis, peritonitis, meningitis, sepsis and recurrent bacteremia. Upon further discussion with the patient, she was found to have a recent pet dog. CONCLUSIONS: High level of clinical suspicious is needed in patient presenting with recurrent pneumonia with chest imaging findings suggestive of multifocal pneumonia. The mainstay of treatment for PJP is TMP-SMX and steroid. We recommend Fluoroquinolones or tetracycline for Bordetella bronchiseptica pneumonia. Reference #1: Benfield T, Atzori C, Miller RF, Helweg-Larsen J. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review. J Acquir Immune Defic Syndr. 2008 May 1;48(1):63-7. Reference #2: de la Fuente J, Albo C, Rodríguez A, Sopeña B, Martínez C. Bordetella bronchiseptica pneumonia in a patient with AIDS. Thorax. 1994 Jul;49(7):719-20. doi: 10.1136/thx.49.7.719. PMID: 8066571;PMCID: PMC475067. DISCLOSURES: No relevant relationships by Priya George No relevant relationships by ELINA MOMIN No relevant relationships by Mohammedumer Nagori

COVID-19 and antibacterial therapy in the inpatient settings: to whom, when, why?

Although antibiotics (ABs) are ineffective against COVID-19, they are often prescribed to patients with the new coronavirus infection. Many of these prescriptions are uncalled for. The aim of the work is to assess the frequency of prescribing antibiotics to hospitalized patients with confirmed COVID-19, identify the most commonly prescribed ABs, and determine the significance of various biomarkers for the diagnosis of bacterial infection. Methods. A retrospective analysis of 190 inpatient cases with confirmed COVID-19 was carried out. The records of COVID-19 patients who were admitted to the intensive care unit were excluded from the analysis. Two groups were formed: 30 patients (group 1) with COVID-19, emergency or elective surgery, and exacerbation of chronic infectious diseases, and 160 patients (group 2) with manifestations of COVID-19 only. Results. ABs were prescribed to 189 patients upon admission to the hospital. The most frequently prescribed ABs included macrolides (63.5%), respiratory fluoroquinolones (49.7%), and third or fourth-generation cephalosporins (57.1%). ABs were administered starting from the first day of admission and until the discharge. The patients in group 2 were more often prescribed respiratory fluoroquinolones and, less often, III – IV generation cephalosporins. Moreover, macrolides were used in the treatment regimens of both groups. Longer administration of respiratory fluoroquinolones to patients in group 2 than patients in group 1 (p < 0,05) was noted. Group 2 also tended to receive longer therapy with macrolides. On admission, the patients with signs of bacterial infection had more significant leukocytosis with a neutrophilic shift, a more common increase in ESR of more than 20 mm/h and an increase in the level of procalcitonin ≥ 0,5 ng/ml. Conclusion. ABs were administered to the overwhelming majority of hospitalized patients in the absence of clear therapeutic indications. The ABs are likely to have a minimal benefit as empirical treatment of COVID-19 and are associated with unintended consequences, including adverse effects and increased antibiotic resistance. According to our data, the most informative markers of a secondary bacterial infection in patients with COVID-19 are leukocytosis with a neutrophilic shift, an increase in ESR of more than 20 mm/h, and a procalcitonin level of more than 0,5 ng/ml.

Antimicrobial Utilization Trends during the COVID-19 Pandemic Throughout the US

Introduction: The purpose of this study is to evaluate the trends of use of various antimicrobials prior to and during the coronavirus disease 2019 (COVID-19) pandemic, which is caused by a coronavirus and is unaffected by antimicrobials. Despite the inactivity of antimicrobials against COVID-19, they are still employed due the possibility of underlying or 'just in case' scenarios of bacterial infection. Research Question or Hypothesis: We hypothesis that the utilization rates of common intravenous antimicrobials correlate to the number of hospitalized COVID-19 patients. Study Design: Retrospective evaluation. Methods: This study utilized de-identified data and was exempt from requiring IRB approval. The antimicrobial utilization was collected through the National Center for Advancing Translational Sciences (NCATS) National COVID Cohort Collaborative (N3C) from 01/01/2019 to 12/31/2021. Antimicrobials of interest included carbapenems, 3rd/4th generation cephalosporins, fluoroquinolones, and piperacillin-tazobactam. Antimicrobial utilization rate was measured using the metric days of therapy (DOT) and patient days. Results: Ten antibiotics were evaluated in this study and accounted for 7,891,986 DOT over three years. Monthly antibiotic utilization (mean±SD per 10,000 patient days [PD]) in 2019 (28.3±13.9) was significantly higher than 2020 (10.8±1.5) and 2021 (12.1±5), p<0.001. All the antibiotics evaluated had significant decreases in utilization with the exception of ceftriaxone (CRO) and piperacillin-tazobactam (TZP). Monthly CRO utilization (mean±SD per 10,000 patient days) in 2019 (3.11±0.32) and 2020 (3.18±0.23) were similar, but higher than 2021 (2.88±0.29), p=0.16. TZP had a similar DOT/10,000PD trend where utilization in 2019 (2.1±0.39) and 2020 (1.8±0.09) were constant and higher than 2021 (1.61±0.08), p<0.001. There is a negative correlation between COVID-19 cases and antibiotics evaluated, r = -0.655, p<0.001. Conclusion: The antimicrobial utilization decreased during the years 2020-2021 with the exception of CRO and TZP. We plan to develop a model to determine the influence of COVID-19 on antibiotic prescribing and evaluate antimicrobial use based on US regions.

Analysis of the impact of a safety measure on systemic (fluoro)quinolones prescriptions and dispensing and on reported adverse reactions in France

Introduction: A re-evaluation of quinolones by the European Pharmacovigilance Risk Assessment Committee (PRAC) in 2018 led to a restriction of their indications in April 2019 [1], due to the risk of serious adverse reactions. We aimed to evaluate the impact on quinolone prescriptions, dispensations, reported adverse events and switch to other classes of antibiotics. Material and methods: From 2018 to 2020, we extracted medico-administrative data from two French Insurance databases (Open Medic® and Medic'AM®) and reported adverse reactions (RAR) from Vigibase® from January 1, 2017, to April 10, 2019, and from April 11, 2019, to July 31, 2021. Results: The annual proportion of quinolones packages reimbursed among all systemic antibiotics was 5.3% in 2018, 4.6% in 2019, 5.0% in 2020. From 2018 to 2020, quinolones were slightly less prescribed by general practitioners (from 65.6% of the quinolone prescriptions to 62.5%) while the opposite was observed among hospital-based physicians (22.2% to 25.2%). There was a decrease in the number of packages of all systemic antibiotics reimbursed during the period, including quinolones. Among quinolone treated patients, the proportion of patients over 60 years-old slightly increased (49.9% to 52.5%).In VigiBase® the proportion of RAR affecting subjects over 65yo increased between the two periods (from 26,8% to 45.5%). The safety profile was similar in musculoskeletal (3.6% versus 3.4%) and in nervous (1.0%versus 1.0%) System Organ Class disorders between the two periods. Discussion/Conclusion: According to our results, there was no major impact of authorities' measure on quinolone prescriptions and dispensations and on RAR. However, our method was limited by the evolution of the number of packages delivered following the seasonality like all other systemic antibiotics, and particularly during this COVID pandemic. Further studies must be conducted to assess the impact of those measures on antibiotics prescription.

Antibacterial Therapy of Patients With COVID-19 During The Outpatient and Hospital Stages

Although antibiotics (AB) are ineffective for the treatment of COVID-19, they are often prescribed to patients with the novel coronavirus infection (NCV) for a variety of reasons. They include the difficulty of excluding bacterial co-infection at the first contact with the patient, as well as the possibility of developing a secondary bacterial infection. The aim of the work is to assess the frequency and background of prescribing antibiotics to hospitalized patients with confirmed COVID-19. Material and methods. A retrospective analysis of 160 hospital records of patients with confirmed COVID-19, who were treated in various Infectious Diseases Departments during the period from September to October 2020, was carried out. The selection was done by the method of random sampling. The analysis did not include the records of patients admitted to the ICU for NCV. Results. Information aboutthe appointment of antibacterial drugs before hospitalization was found in 109 patients, of which only 51 patients did not receive AB on an outpatient basis. The remaining 58 (53.2%) patients began taking ABs on their own or based on the recommendation of an outpatient doctor, including 31 patients who took two or more drugs (successively or simultaneously). The most commonly used antibiotics were: macrolides (37 patients), cephalosporins (24 patients), respiratory fluoroquinolones (12 patients), and aminopenicillins (5 patients). On admission, AB was prescribed for almost all patients, except for one. The most frequently prescribed antibiotics were: macrolides (61%), mainly azithromycin, and respiratory fluoroquinolones (54.1%), mainly levofloxacin. In most cases, these drugs were combined with 3rd or 4th generation cephalosporins. Most patients received more than one AB: two drugs were prescribed to 86 (54.1%) patients, three - to 34 (21.4%) patients. AB therapy was carried out for a long time: the maximum number of days for macrolide administration (excluding previous AB therapy at the outpatient stage) was 16 days, respiratory fluoroquinolones - 22 days, 3rd generation cephalosporins - 19 days, 4th generation cephalosporins - 17 days, carbapenems - 34 days. In almost 100% of cases, ABs were prescribed on the first day of admission of patients, and their therapy continued until the patient was discharged from the hospital. Conclusion. The appointment of antibiotics at the hospital stage was established for the vast majority of patients in the absence of clear indications for their appointment. Such a frequent prescription of antibiotics is accompanied by a number of problems: immediate - side effects of such therapy (for example, antibiotic- associated diarrhea), long-term - an increase in antibiotic resistance of microorganisms.

Basophil activation test: current applications and future perspectives

The basophil activation test (BAT) is a flow cytometric assay that evaluates the percentage of activation or degranulation of peripheral blood basophils, after “in vitro” exposure to specific allergens. In sensitized patients, the stimulation of peripheral blood basophils with a specific allergen induces or up-regulates the expression of molecules, such as CD63 and CD203c, which represent, markers of degranulation and activation of basophils, respectively. The validity of the BAT requires a negative control (sterile saline) and a positive control (anti-IgE molecules). Several studies have demonstrated the role of the BAT in supporting the diagnosis of drug, food and hymenoptera venom allergy. The BAT has shown a low sensitivity but good specificity in diagnosing allergy to drugs such as NSAIDs, beta-lactam antibiotics, quinolones and muscle relaxants. In food allergy, the sensitivity and specificity of the BAT depends on the food;in the case of peanut allergy the sensitivity reaches 96% while the specificity the 100%. In addition, the BAT is an useful tool to monitor the natural resolution of allergies and the clinical effects induced by either immunotherapy or anti-IgE treatment. Finally, the BAT has been utilized to study the pathogenetic mechanisms underlying several IgE-mediated diseases. For example, in patients affected by severe bronchial asthma, the BAT has demonstrated the ability of Staphylococcus aureus enterotoxins to induce the activation of basophils supporting the role of these enterotoxins as “triggers” of the inflammatory cascade in bronchial asthma. In patients with cystic fibrosis the BAT can be used to dis-criminate allergic bronchopulmonary aspergillosis from Aspergillus colonization. More recently, the BAT has been demonstrated as a potential diagnostic tool to evaluate allergy to the polyethylene glycol (PEG) present in the anti-SARS-CoV-2 BNT162b2 mRNA vaccine.

Outbreak of Multidrug-resistant Pseudomonas aeruginosa in a Tertiary Healthcare System in Detroit

Background. Pseudomonas aeruginosa is one of the most common causes of healthcare-associated infections in critically ill patients and those with suboptimal immunity. However, the development of multidrug resistant Pseudomonas aeruginosa (MDR Pa) creates an even great disease burden and threat to both the hospital and local community health. The purpose of this study is to illustrate a descriptive analysis of a cluster of MDR Pseudomonas, during a local surge of SARS-CoV-2 (COVID 19) pandemic. The goal is to shed more light on the troublesome parallel during outbreaks, such as COVID-19 and consequential secondary outcomes. Methods. From November 2020 through February 2021, 16 patients exposed to the intensive care units of a tertiary healthcare system were infected or colonized with a multidrug-resistant strain of P. aeruginosa (Figure 1). Outbreak investigation was conducted via retrospective chart review of the first eight cases and prospective analysis of the latter eight cases. The isolates collected prospectively were analyzed for taxonomic identification, antimicrobial resistance profile, and phylogenetic analysis. Clinical characteristics of all patients were collected, and epidemiological investigation was carried out. MDR is defined as resistance to at least four classes of antibiotics: third-generation cephalosporins, fluoroquinolones, aminoglycosides, and carbapenems. Results. Of the 16 cases of MDR Pa infections, seven died within five months (Table 1). Antimicrobial resistance gene profiling detected blaOXA and blaPAO betalactamase genes in all the samples. One sample contained an additional blaVIM resistance gene, although this patient was colonized and not actively infected. The analysis suggests existence of two clusters demonstrating relatedness and possible horizontal transmission. Timing of this cluster of cases coincides with surge of COVID-19 cases. This highlights the importance of infection control measures and antimicrobial stewardship. Conclusion. Since early 2017 studies show there is a growing prevalence worldwide in transferable resistance, particularly for β-lactamases and carbapenemases, MDR Pseudomonas. This study emphasizes an irony paralleled during a pandemic, the needed efforts to prevent unintentional lapses in patient safety.

POSC218 Study of Antibiotic Consumption Trends in Public Pharmacies during the COVID-19 Pandemic in Ukraine

Objectives: European studies showed, up to 70% of patients with COVID-19 received antibiotics. In Ukraine, due to the Order of MoH of Ukraine dated 31.12.2020 3094 there is a requirement that antibiotics are contraindicated, they can prescribe only in the presence of laboratory-confirmed bacterial infection or with reasonable suspicion. The study aim was to assess current trends in the consumption of antibiotics in pharmacies during COVID-19 pandemic. Methods: A survey "Assessment of the antibiotic consumption and need for e-prescriptions during the COVID-19 pandemic" was developed. The survey was conducted during postgraduate education using the Google platform. We send 225 and received 205 completed surveys from pharmacists, who have from 5 up 40 work experience years (directors, managers of pharmacies, general pharmacists) from 5 regions of Ukraine. Results: We found that the consumption of antibacterial medicines in 2020, compared to 2019, increased by 50,5%. There were such antibiotics in the greatest consumption: beta-lactames 66.1%;respiratory fluoroquinolones 19.2%;macrolides 14.7% for outpatientsfrom public pharmacies. The analysis showed the most often consumed antibiotics were: azithromycin (65.4%), cefoperazone;(47.6%), cefipim (42.3%), piperacillin sodium, tazobactam sodium (27.5%), meropenem (15.2%). We found that 79.1% of pharmacists consider necessary to more strictly monitoring of the antibiotic prescribing by family doctors. There are 97.5% of pharmacists consider it necessary to release e-prescriptions,reimbursement of antibiotics. Conclusions: A Pharmacist Protocol for the symptomatic treatment of uncomplicated forms of COVID -19 has not yet been introduced in Ukraine, but 83.1% o of pharmacists considered that this protocol is necessary for good pharmacy practice in pandemic. There is prospective to implement e-prescriptions of antibiotics from pharmacies and reimbursement during a COVID-19 pandemic. Pharmacists indicated that patients often take antibiotics without a prescription, which can lead to develop of antibiotic resistance and an increase in the treatment cost in future.

Treatment and in-Hospital Overall Survival in Hematological Patients with Grade 4 Neutropenia and Coronavirus Infection

Background: According to published data, the risk of coronavirus infection (COVID-19) in patients with malignancies is 5 times higher than in those without malignancies. Objective: To evaluate in-hospital overall survival in hematological patients with grade 4 neutropenia associated with coronavirus infection. Patients: This study was conducted from April 24, 2020 to June 17, 2021 in the Department of Hematology of Moscow City Clinical Hospital No. 52 (Russian Federation) and included 76 hematological patients with grade 4 neutropenia and coronavirus infection (aged 18-91 years): • 40 patients with acute leukemias (32 with AML, 8 with ALL): 22 men with a median age of 54 years (interquartile range (IQR) 43-60) and 18 women with a median age of 61 years (IQR 56-70) and • 36 patients with lymphoproliferative diseases (mostly with aggressive non-Hodgkin's lymphomas): 13 men with a median age of 57 years (IQR 40-68) and 23 women with a median age of 63 years (IQR 35-75). All patients were brought in by ambulance from other hospitals where they had received a course of combination chemotherapy interrupted due to coronavirus infection. Results: Most pts had moderate to severe lung disease (CT severity scores were 2, 3, and 4 in 29 (38.2%), 17 (22.5%), and 8 (10%) patients, respectively);55% of patients had high C-reactive protein and procalcitonin (above 0.5 ng/mL);lactate dehydrogenase (mean 395.7 U/L) and D-dimer (mean 2533.8) levels were significantly elevated. Patients had a higher NEWS score (mean 8) and a high Charlson comorbidity index score (mean 5). Interleukin-6 and IL-1b blockers were used as pathogenetic therapy to control hypercytokinemia. Taking into account grade 4 neutropenia, the dose of interleukin blockers was reduced. In order to prevent thromboembolic complications, low molecular weight heparins were used at therapeutic doses (with anti-Xa activity monitoring). Oxygen was administered in patients with clinical signs of respiratory failure (oxygen insufflation via nasal cannulas or mask). Patients with progressive respiratory failure were transferred to intensive care unit. In order to improve humoral immune response (due to low SARS-CoV-2 IgG antibody titers), 43.4% of patients were administered replacement therapy with pathogen-reduced fresh-frozen COVID-19 convalescent plasma. This led to a pronounced IgG increase in 7 patients only. Antifungal treatment was used in 54% of cases. Empirical antibacterial treatment for community-acquired pneumonia was administered, including inhibitor-protected aminopenicillins and respiratory fluoroquinolones (as 1st line treatment), upfront antibacterial treatment for neutropenic fever (2nd line), and targeted antibacterial treatment (3rd line). • In the acute leukemia group, 25 (63%) patients died during hospital treatment and 15 (37%) subjects survived;the median overall survival was 15 days (95% CI 15-22) (Fig. 1). • In the lymphoproliferative disease group, the numbers of deaths and survivals were 22 (61%) and 14 (39%), respectively, and the median overall survival was 25 days (95% CI 11-32) (Fig. 2). The median follow-up was 24 days. Conclusions: Coronavirus infection associated with severe neutropenia (caused by tumor progression and/or combination chemotherapy) is a significant adverse factor for overall survival in patients with hematological malignancies. [Formula presented] Disclosures: No relevant conflicts of interest to declare.