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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.
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A 5-month-old, intact male, yellow Labrador retriever was presented with a 24-hour history of anorexia and vomiting. Abdominal imaging revealed the presence of a mechanical obstruction in the jejunum and peritoneal effusion. Cytologic evaluation and culture of the effusion prior to surgery identified a suppurative exudate with bacteria consistent with septic peritonitis and suspected to be related to the intestinal lesion. An exploratory laparotomy was performed, and a segment of jejunum was circumferentially severely constricted by an off-white, fibrous band of tissue. Resection and anastomosis of the strangulated segment of jejunum and excision of the constricting band provided resolution of the clinical signs. The dog made a complete recovery. Histologic evaluation revealed the band to be composed of fibrovascular and smooth muscle tissue, consistent with an idiopathic anomalous congenital band. No other gastrointestinal lesions were observed, either grossly at surgery or histologically in the resected segment of intestine. To our knowledge, a similar structure has not been reported in the veterinary literature.Copyright © 2022 Canadian Veterinary Medical Association. All rights reserved.
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Upper respiratory tract infections are responsible for millions of physician visits in the United States annually. Although viruses cause most acute upper respiratory tract infections, studies show that many infections are unnecessarily treated with antibiotics. Because inappropriate antibiotic use results in adverse events, contributes to antibiotic resistance, and adds unnecessary costs, family physicians must take an evidence-based, judicious approach to the use of antibiotics in patients with upper respiratory tract infections. Antibiotics should not be used for the common cold, influenza, COVID-19, or laryngitis. Evidence supports antibiotic use in most cases of acute otitis media, group A beta-hemolytic streptococcal pharyngitis, and epiglottitis and in a limited percentage of acute rhinosinusitis cases. Several evidence-based strategies have been identified to improve the appropriateness of antibiotic prescribing for acute upper respiratory tract infections.Copyright © 2022 American Academy of Family Physicians.
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Case 1 was an 81-year-old man undergoing treatment for the nummular eczema of the lower leg. The day after being administered the first dose of a COVID-19 vaccine, the patient developed generalized pruritus, multiple serous papules, and erythema on the trunk, upper extremities, and palms, as well as worsening of pre-existing eczema on the lower legs. The serum TARC level of the patient was 1,383 pg/mL. After taking oral antihistamines and topical steroids for two weeks, the erythema faded, papules crusted, and serum TARC level normalized. Case 2 was a 22-year-old woman who had been treated with topical steroids for contact dermatitis by poultices on the ankles. On the same day as she received the second dose of COVID-19 vaccine, erythema with pruritus on the dorsum of the feet appeared and gradually expanded to papules and edematous erythema on the face, extremities, and trunk. The serum TARC level of the patient was 2,090 pg/mL. After taking 15 mg/day oral prednisolone and topical steroids for 10 days, overall erythema became hyperpigmented, and the erythema on the dorsum of the hands and fingers persisted for approximately 2 weeks and then became pigmented. Serum TARC level normalized after the skin rash reformed. Case 3 was a 74-year-old woman with a history of asthma. She received SBT/ABPC therapy for acute cholangitis for one week. Ten days after treatment, she received the first COVID-19 vaccination dose. Two days after vaccination, the patient became aware of pruritus on the extremities ipsilateral to the vaccination site, and small erythematous patches appeared all over the body in a disseminated pattern. Her serum TARC level was 3,862 pg/mL. After taking oral antihistamines and topical steroids for 3 weeks, the erythema completely faded, and the serum TARC level normalized. The DLST showed positive by SBT/ABPC, but the result of drug challenge test was negative. There have been no previous case reports of rash with a high TARC level after vaccination. In the future, it is necessary to accumulate patients with a high TARC level by vaccination and analyze the clinical and pathological trends including immunological mechanisms. Copyright © 2022 Osaka University Medical School. All rights reserved.
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SESSION TITLE: Close Critical Care Calls SESSION TYPE: Case Reports PRESENTED ON: 10/18/2022 11:15 am - 12:15 pm INTRODUCTION: With the development of resistant organisms, additional therapies are needed to effectively treat patients with severe infections. The Seraph®-100 Microbind Affinity Blood Filter utilizes immobilized heparinized microbeads, acting similar as the human glycocalyx, to bind and remove these substrates. In vitro and pre-clinical studies have shown up to 99% clearance of Enterococcus faecalis exposed to the Seraph®-100 blood filter. This novel extracorporeal blood purification system could assist with infection source control and reduction of vasopressor requirements. CASE PRESENTATION: A 30-year-old male with no significant past medical history was admitted due to severe ARDS secondary to COVID-19 infection and required extracorporeal membrane oxygenation (ECMO) after an unsuccessful trial of conventional supportive therapies. The patient's hospital course was complicated by multiple infections, including bacteremia from methicillin susceptible Staphylococcus aureus, candidemia and Enterobacter ventilator associated pneumonia. These infections initially improved with use of appropriate intravenous antimicrobials. However, the patient experienced an acute hemodynamic decompensation requiring multiple vasoactive medications. He was empirically started on broad spectrum anti-microbials including meropenem, vancomycin, and isavuconazole. Blood cultures revealed Enterococcus faecalis, susceptible to broad-spectrum antibiotics. After 24 hours of broad-spectrum antimicrobials without improvements in vasopressor requirements, the Seraph-100® blood filter was used in-parallel with the ECMO circuit. Immediate improvement in vasopressors was noted with discontinuation of vasopressin and decrease in norepinephrine by 75%. The patient finished a 2-week course of intravenous ampicillin/sulbactam. His respiratory status subsequently improved and he was able to be removed from ECMO 24 days later. DISCUSSION: Initial studies have shown the Seraph-100 is capable of clearing the SARS-Cov-2 virus and use has been associated with decreased mortality in patients with SARS-Cov-2. The ability to remove additional pathogens including bacteria, fungi and viruses would aid in obtaining source control and augment the effects of intravenous antibiotics. This case not only illustrates the benefits with the use of the Seraph ®-100 blood filter along with broad spectrum antibiotics, but also the ability to use this extracorporeal blood purification system in-line with ECMO. CONCLUSIONS: With the emergence of multi-drug resistant pathogens, additional treatment options are urgently needed. The Seraph®-100 may be a useful adjunct to broad spectrum antimicrobials and may improve hemodynamics in patients with vasopressor-dependent septic shock. Further prospective studies are needed to assess clinical improvements with the use of the Seraph-100 Microbind blood filter in patients with bacteremia and those requiring ECMO. Reference #1: Olson SW, Oliver JD, Collen J, et al. Treatment for Severe Coronavirus Disease 2019 With the Seraph 100 Microbind Affinity Blood Filter. Critical Care Explor. 2020;2(8):e0180. Reference #2: Chitty, Stephen, Mobbs, Sarah, Chung, Kevin et al., for the PURIFY INVESTIGATORS. A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report. medRxiv 2021.04.20.21255810;doi: https://doi.org/10.1101/2021.04.20.21255810 Reference #3: Seffer, Malin-Theres, et al. "Heparin 2.0: a new approach to the infection crisis.” Blood Purification 50.1 (2021): 28-34. DISCLOSURES: No relevant relationships by Joshua Boster No relevant relationships by Henry Danchi Speaker/Speaker's Bureau relationship with Janssen Please note: $1001 - $5000 by Michael Morris, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 by Michael Morris, value=Honoraria Removed 03/29/2022 by Michael Morris No releva t relationships by Mai Nguyen No relevant relationships by Melissa Rosas No relevant relationships by Steven Stoffel No relevant relationships by Robert Walter
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SESSION TITLE: Chest Infections with Pleural Involvement Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Foreign body aspiration (FBA) is an uncommon cause of dyspnea and respiratory infection. 80% of cases occur in children under 15-years-old, with the highest mortality in children under 1 and adults over 75. We present an unusual case of a fingernail clipping causing severe empyema in a middle-aged male. CASE PRESENTATION: A 44-year-old male with diabetes mellitus presented with a 3-day history of dyspnea, productive cough, and anorexia, and a 1-day history of fevers and substernal chest pain. Exam was notable for fever, tachypnea, tachycardia, and hypoxemia requiring a non-rebreather mask. Labs were significant for a negative COVID-19 polymerase chain reaction (PCR) test, white blood cell (WBC) count 17,000 μL, and lactate 3.4 mmol/L. He was given albuterol-ipratropium nebulizer treatments and methylprednisolone 125 mg. Chest x-ray revealed a large right-sided air-fluid level, dense consolidation of the lung base, and complicated pleural effusion. Computed Tomography (CT) of the chest revealed a large right mid-lung abscess, right middle lobe (RML) and right lower lobe (RLL) consolidations, and loculated pleural effusion with hydropneumothorax. A surgical chest tube was placed that drained purulent fluid. The effusion grew Klebsiella pneumoniae, which was treated with ampicillin-sulbactam. Repeat CT chest revealed improved loculated effusion, but persistent RML and RLL consolidations with concern for endobronchial obstruction. Flexible bronchoscopy was performed, which identified and removed a human fingernail clipping obstructing the RML. Post-procedure, his oxygen requirements, cough, and dyspnea improved remarkably. He was discharged with a 4-week course of amoxicillin-clavulanate. On outpatient follow-up 6 weeks later, he was asymptomatic. DISCUSSION: In our patient, a fingernail clipping was lodged in the opening of the RML, resulting in a post-obstructive pneumonia complicated by empyema. Post-bronchoscopy, the patient admitted to anxiety-induced nail-biting. FBA most commonly occurs in the right bronchial tree (71.5%) as compared to the left bronchial tree (22.8%) and trachea (5.7%). Objects were most commonly lodged in the bronchus intermedius (27%) and right lower lobe (33%). Foreign bodies can be removed via rigid or flexible bronchoscopy, with a 90% success rate in the latter. Instruments such as forceps and baskets can be used to remove the foreign body, and Trendelenberg positioning can be useful in moving the object proximally. In up to 76% of cases, granulation tissue caused by a localized reaction to the foreign body may occur and can be minimized with systemic steroids for 24 hours. CONCLUSIONS: FBA in a middle-aged patient is an unusual cause of respiratory infection, but should be on the differential diagnosis for post-obstructive pneumonia. Reference #1: Hsu Wc, Sheen Ts, Lin Cd, Tan Ct, Yeh Th, Lee Sy. Clinical experiences of removing foreign bodies in the airway and esophagus with a rigid endoscope: a series of 3217 cases from 1970 to 1996. Otolaryngol Head Neck Surg. 2000 Mar;122(3):450-4. doi: 10.1067/mhn.2000.98321. PMID: 10699826. Reference #2: Blanco Ramos M, Botana-Rial M, García-Fontán E, Fernández-Villar A, Gallas Torreira M. Update in the extraction of airway foreign bodies in adults. J Thorac Dis. 2016;8(11):3452-3456. doi:10.21037/jtd.2016.11.32. Reference #3: Fang YF, Hsieh MH, Chung FT, Huang YK, Chen GY, Lin SM, Lin HC, Wang CH, Kuo HP. Flexible bronchoscopy with multiple modalities for foreign body removal in adults. PLoS One. 2015 Mar 13;10(3):e0118993. doi: 10.1371/journal.pone.0118993. PMID: 25768933;PMCID: PMC4358882. DISCLOSURES: No relevant relationships by Nuzhat Batool No relevant relationships by Lisa Glass No relevant relationships by Alice Mei No relevant relationships by Daisy Young
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Introduction: Abdominal pain is one of the most common complaints seen in the pediatric acute care setting. SARS-CoV-2 disease in children includes a hyperinflammatory syndrome called Multisystem Inflammatory Syndrome in Children (MIS-C). Gastrointestinal symptoms are most common in pediatric acute SARS-CoV-2 infection as well as in MIS-C. Case Description: A 13- year-old female presented with diffuse lower abdominal pain for 3-days. Pain was 10/10 in intensity, worsened with movement, and had associated constipation, anorexia, nausea, and vomiting. Exam showed an ill-appearing female with labile vitals and generalized lower abdominal tenderness with good bowel sounds. Ultrasound suggested features of acute appendicitis but a follow-up CT did not visualize the appendix. She was admitted to the inpatient unit after routine screening revealed positive SARS-CoV-2 antibody but negative PCR. She received IV fluid bolus, narcotic analgesics, and ampicillin-sulbactam preoperatively. Within hours, she spiked high-grade fevers (101.4F), sustained hypotension, and tachycardia with concern for sepsis secondary to a possible ruptured appendix. She underwent emergency diagnostic laparoscopy which revealed bile-tinged fluid in the lower quadrant, a mildly inflamed appendicular tip without perforation, and thickened mesenteric nodes within the inflamed distal ileum. Intra-operatively, she had persistent hypotension requiring fluid boluses and vasopressors. Her admission labs revealed elevated inflammatory markers, deranged coagulation profile, and elevated cardiac enzymes. Her differential diagnosis was then revised to include MIS-C and severe sepsis. Antibiotic coverage was broadened to Vancomycin and Meropenem. An Echocardiogram showed mitral regurgitation with moderately to severely decreased right and left ventricular systolic dysfunction with an ejection fraction of 32.8% The patient was then transferred to the pediatric cardiac critical unit where she received treatment with IVIG, steroids, and anticoagulants. Her clinical status and lab studies improved with EF > 50%. She was discharged from the intensive care unit after 7 days and has had an uneventful follow-up. Discussion: Differential diagnosis for acute lower abdominal pain in an adolescent female is broad. Similar cases with predominant GI symptoms and later generalized multisystem involvement have been reported, however, most were managed conservatively. Two reports have been published on MIS-C presenting as acute appendicitis, but neither had significant cardiac involvement. Our patient's presentation can easily be confused with an acute surgical abdomen but the pathology report confirmed a congested appendix without any fecoliths supporting either inflammation or vasculitis as the cause for her presentation, which is in concordance with the hyperinflammatory state that has previously been described in patients presenting with a history of past SARS-CoV- 2 infections. Conclusion: MIS-C can mimic serious pediatric illnesses including sepsis, acute abdomen, and Kawasaki disease. Clinicians should have a low threshold for suspecting MIS-C, as prompt treatment can be lifesaving. Universal screening for COVID-19 infection with PCR and antibody tests can expedite the diagnostic evaluation of severely ill children. Showing reactive wall thickening of the cecum and small bowel loops (red arrow) and enlarged mesenteric lymph nodes (yellow arrow). The appendix could not be visualized here.
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Introduction: Described by Dr. Andre Lemierre in a 1936 case series of 20 patients, Lemierre Syndrome (LS) is defined as a septic thrombophlebitis of the internal jugular vein (IJV). LS typically begins as an oropharyngeal infection that advances to the IJV through direct extension through the fascial planes of the neck, or indirect lymphatic or hematogenous spread from the peritonsillar vessels. We present a case of LS in a 4-year-old patient who presents much younger than the typical age range of affected individuals, and who recovered well without any longterm sequelae. Case Description: A 4-year-old ex-27 week female presented with a near 3 week history of intermittent fevers and progressive right-facing torticollis. She had multiple interactions with the health care system over her illness course, and was given diagnoses ranging from general viral syndrome to gingivostomatitis and acute otitis media. Around the 2 week mark, her caretaker described her as having developed a “crick” in her neck while consistently favoring a rightward tilt. On illness day 16, she presented to her pediatrician for routine visit, and was noted to have fever, right tonsillar enlargement, and cervical lymphadenopathy, thereby prompting referral to the emergency department. Her physical exam on admission was additionally significant for a 30 degree rightward head rotation, a swollen and tender right sternocleidomastoid, and submandibular lymphadenopathy. She was resistant to active or passive neck rotation due to discomfort, but was able to traverse the midline with coaxing. Laboratory workup was notable for leukocytosis and thrombocytosis with elevated inflammatory markers, as well as mild transaminitis. Infectious serologic workup was negative for: SARS-CoV-2, Bartonella henselae, Bartonella quintana, EBV, and Mycoplasma. Blood culture showed no growth, but was drawn after antibiotics were given. A CT neck with contrast demonstrated intrinsic occlusion vs compression of the right IJV, and ultrasound and MRI confirmed IJV thrombophlebitis. Discussion: LS is typically associated with Fusobacterium necrophorum infection, a gram-negative anaerobe, with incidence estimated to be around 1 to 3.6 per million per year and mortality rate around 5 to 9%. Significant morbidity is often present, due to dissemination of septic thromboemboli, potentially affecting the CNS, bones/joints, and lungs. The typical age range for LS in pediatric patients clusters around adolescence, but infants as young as 6 months of age have been reported. As oropharyngeal infections most often precede LS, it is important to keep this rare but serious infection on any differential. Conclusion: This patient was diagnosed with Lemierre Syndrome. She was treated with an inpatient course of ampicillin/sulbactam before transitioning to oral amoxicillin/clavulanic acid to complete a total of 4 weeks of antibiotic therapy. All elevated laboratory markers normalized prior to hospital discharge, and the patient had complete resolution of symptoms at outpatient follow up.
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Klebsiella pneumoniae is a common bacterial pathogen causes wide range of infections all over the world. The antimicrobial resistance of K. pneumoniae is a global concern and expresses several virulence factors contributing to the pathogenesis. The incidences of bacterial co-infection in viral pneumonia are common. Increased risk of K. pneumoniae co-infection in viral respiratory tract infection should be alerted in COVID-19 pandemic period. The study aims to detect the association between antimicrobial resistance and factors causing pathogenicity of K. pneumoniae. For the current study, 108 K. pneumoniae clinical isolates were included. Antimicrobial susceptibility test was done by Kirby-Bauer disc diffusion method according to CLSI guidelines. Virulence factors such as biofilm formation, haemagglutination, haemolysins, hypermucoviscocity, siderophore, amylase, and gelatinase production were determined by phenotypic method. In this study K. pneumoniae showed high level of antimicrobial resistance towards ampicillin (92.59%) followed by amoxicillin-clavulanic acid (67.59%) and cotrimoxazole (47,22%). An important association between biofilm formation and antimicrobial resistance was found to be statistically significant for cotrimoxazole (P-value 0.036) and amoxicillin-clavulanic acid (P-value 0.037). Other virulence factors like hypermucoviscocity, haemagglutination, amylase, and siderophore production were also showed a statistically significant relation (P-value <0.05) with antimicrobial resistance. Further molecular studies are necessary for the identification of virulence and antimicrobial resistance genes, for the effective control of drug-resistant bacteria.
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Introduction: The novel coronavirus (2019-nCoV) is a contagious virus that causes respiratory infection and has shown evidence of human-to-human transmission. In this infection the immunity of the patient is decreased;making them susceptible to various secondary infections. This leads to increased morbidity and mortality in these patients. Aim: To estimate the profile of secondary infections in hospitalised Coronavirus Disease-2019 (COVID-19) patients and analyse their antimicrobial susceptibility pattern. Materials and Methods: A cross-sectional study was conducted for a period of five months from June to October 2021, which included COVID-19 positive patients with secondary infection admitted in the dedicated COVID hospital, Maharaja Krishna Chandra Gajapati Medical College and Hospital (MKCG MCH), Berhampur, Odisha, India. Clinical samples like blood, urine, sputum, tissue biopsy and Bronchoalveolar Lavage (BAL) were collected aseptically from patients with COVID-19 and were processed in microbiology laboratory as per standard operating procedures. All the necessary information like demographic features (age, gender), associated co-morbidities and oxygen saturation levels of COVID-19 positive patients at the time of admission were collected and entered in a Microsoft Excel sheet for further analysis. Results of continuous variables were described by mean and range while categorical variables were described by frequency. All the generated data was analysed by Statistical Package for the Social Sciences (SPSS) 16.0. Results: A total of 438 patients suspected of COVID-19 were admitted during the study period, out of which 138 patients were positive for COVID-19 by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Out of 138 COVID-19 positive patients, 105 patients were willing to give samples and their samples were processed for bacterial and fungal culture and sensitivity. Total 18/105 (17.1%) samples were positive for bacterial and fungal growth. Blood Stream Infection (BSI) were seen in 14/18 (77.8%) and was predominantly associated with Staphylococcus aureus 5/14 (35.7%), followed by Enterococcus spp. 3/14 (21.4%). Out of total culture positive cases, 2/18 (11.1%) showed Urinary Tract Infection (UTI). Of the UTI cases Escherichia coli was isolated from 1/2 (50%) of cases. Out of total culture positive cases, 2/18 (11.1%) were identified having mucormycosis. All gram positive bacteria had shown maximum resistant to ampicillin and gram negative bacteria were resistant to ampicillin-sulbactam, levofloxacin, cotrimoxazole. Conclusion: In COVID-19 positive patients with secondary infection, early diagnosis and prompt treatment will lead to improved patient care and better outcome.
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Background. Tocilizumab is an interleukin-6 monoclonal antibody with widespread use in rheumatologic conditions. Observational studies have shown a promising role of Tocilizumab in severe COVID-19 patients with cytokine storm syndrome. Data about tocilizumab use in pregnant patients is limited. We report two outcomes of two pregnant patients with COVID-19 in the second trimester who received tocilizumab Methods. A 24-year-old 20 weeks pregnant lady with a history of asthma and gestational diabetes mellitus presented with three days history of fever, cough and shortness of breath (Figure 1). She was clinically stable but later developed ARDS and developed increased oxygen demand up to 10 liters/min. She received Tocilizumab on. Patient was observed in a high dependency unit but did not require mechanical ventilation. Patient was discharged home with full recovery and later delivered a healthy baby. Timeline of medicines used during hospital (Figure 2). Case 2: 39-year-old 23 weeks pregnant lady presented with seven days history of fever cough and shortness of breath (Figure 1). On presentation, she had progressive worsening hypoxic respiratory failure and was intubated. Patient had her nasopharyngeal swab for CODI-19 RT PCR was positive. The patient had severe ARDS requiring ECMO (extracorporeal membrane oxygenation) for respiratory support. Tocilizumab 400 mg was given on the presentation, along with other medications (Figure 3). Patient had regular monitoring of fetus;however, she had intrauterine fetal demise on day 14. Patient It is unclear if IUFD was due to using of tocilizumab or severity of COVID19 itself. The patient stayed in ICU for 20 days and was discharged after full recovery. Figure 1. Case 1 treatment timeline. Abberviations: Azithro: Azithromycin, HCQ: Hydroxychloroquine, CQ: Chloroquine, LPV/r: lopinavir/Ritonavir, Osel: Oseltamivir, MP: Methylprednisolone, Ampi-sulb: Ampicillin-sulbactam, TCZ: tocilizumab Figure 2. Case 2 treatment timeline Results. Learning points: Tocilizumab use in pregnant patients with severe COVID-19 pneumonia during the second trimester improved maternal outcomes in our cases. Tocilizumab use may be associated with worse fetal outcomes, including intrauterine fetal demise (IUFD). Conclusion. The pharmacological management of pregnant patients with severe COVID-19 pneumonia poses significant challenges. The use of Tocilizumab may improve maternal outcomes but may also increase the risk of worse fetal outcomes. Caution should be exercised in using this agent, and risks and benefits should be discussed with the patients.