Placing Antimicrobial Resistance in the Context of Competing Public Health Priorities in Sub-Saharan Africa, a Perspective from Malawi

Antimicrobial resistance is a major threat to human health that is predicted to impact most heavily on sub-Saharan Africa, however there is a lack of clinical outcome data from drug-resistant infections in this setting. There are reasons to expect the COVID-19 pandemic to have both positive and negative impacts on AMR in Africa. We have recruited a series of prospective longitudinal cohorts from Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi and the surrounding communities in the Southern Region of Malawi. The data from these cohorts has been used to describe the aetiology of febrile illness, the burden of antimicrobial resistance in this setting and the distribution of extended spectrum beta-lactamase producing bacteria in humans, animals and the environment. Amongst a cohort of patients presenting to QECH unwell with febrile illness, 67% were living with human immunodeficiency virus (HIV). We identified a diagnosis in 145 of 225 (64%) participants, most commonly tuberculosis (TB;34%) followed by invasive bacterial infections (17%), arboviral infections (13%), and malaria (9%). In a second cohort with drug resistant infection, resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1.44, 95% CI 1.02-2.04), longer hospital stays (1.5 days, 1.0-2.0) and decreased probability of discharge alive (HR 0.31, 0.22-0.45). In the community cohorts, a paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites and ESBL-Enterobacterales were isolated from 41.8% of human stool, 29.8% of animal stool and 66.2% of river water samples and was associated with the wet season, living in urban areas, advanced age and in household-animal interactions. Life threatening febrile illness is common in Blantyre however, diagnostics are few, however the COVID-19 pandemic has led to rapid expansion of diagnostic capacity. We are, however frequently treating the wrong bugs with ceftriaxone, further there was significant expansion of azithromycin demand and usage during the pandemic. Current management of sepsis has not been optimised and ceftriaxone use is promoting carriage of ESBL bacteria out of the hospital and ESBL E. coli and K. pneumoniae are ubiquitous in the community, where environmental hygiene infrastructure and community antimicrobial stewardship are critically lacking.Copyright © 2023

Clostridium Difficillae Infection in Post-Covid Patients

Intro: The ongoing pandemic caused by the SARS-CoV-2 virus has brought many new insights into medicine. During the first months of the pandemic, when there were no comprehensive guidelines for precise antimicrobial therapy, empirical overuse of broad-spectrum antibiotics was observed. Which resulted in the development of clostidium infection in certain cases. In our report, we address 83 cases of clostridial colitis in post-covid patients from 3/2020 to 3/2021 and their specific therapy. Method(s): Retrospective analysis of risk factors for clostridial infection and therapy of clostridial colitis. Finding(s): In the period 3/2020-3/2021, 9617 patients were diagnosed with SARS-CoV-2 virus infection in our hospital, of which 1247 were hospitalized. In 83 cases, clostridial colitis occurred during or after the covid infection had resolved. Mortality in this group was 17%, which corresponds to 14 patients. Previous empirical administered antiobiotics in COVID-19 infection contributed to the development of clostridial colitis in case of 22 patients (27%) by clarithromycin, in 14 pacients (17%) by penicillins and by 3rd generation cephalosporins in 9 patients (11%). The average duration of therapy with broad-spectrum antibiotics was 15.63 days (+-8.99). Other risk factors we observed are: PPI use (25%), active malignant disease (10%), previous glucocorticoid therapy (22%). Vancomycin was used in clostridial infection therapy in 47% (39), metronidazole in 31% (25) and fidaxonicin in 7% (6). In the group, we observed recurrence of clostridium difficile infection in 14% of patients and FMT was performed in 6 patients. Conclusion(s): This study shows a higher percentage of clostridial infection in cases of long-term therapy with broad-spectrum antibiotics. It also points to the effect of specific antimicrobial therapy for infection caused by the bacterium Clostridium difficile and the possibility of using fecal bacteriotherapy.Copyright © 2023

Evaluation of risk factors associated with mortality in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa with difficult-to-treat resistance

Introduction: Evaluation of prognostic factors in patients with ventilator- associated pneumonia (VAP) due to P. aeruginosa. The effectiveness of novel antipseudomonal antibiotics was reviewed. Method(s): Retrospective, single-center cohort analysis between April 2018 and June 2022. Data were obtained from the ENVIN-HELICS and electronic medical records. Demographic variables, underlying diseases and diagnosis to admission were registered. We considered each treatment appropriate according to Tamma PD et al. [1] criteria. We registered ventilator-associated tracheobronchitis (VAT) and pneumonia (VAP) episodes together with the recurrency of the infection. Result(s): From 61 patients included, 77% were admitted for ARDS due to COVID-19. The mean APACHE-II was 14.3 +/- 6.6. 7 patients required ECMO and 4 required RRT. The median length of stay in the ICU was 52 (ICR 36-84) days. 91 respiratory infections were recorded: 60 VAP and 31 VAT. On the first episode, carbapenem-resistance to meropenem was 40%;rising up to 58% on the second one. 6 patients developed a third episode (VAT) with a 100% of carbapenem- resistance. 13 (14%) respiratory infections showed resistance to the novel beta-lactamase inhibitor cephalosporins (8 to ceftalozanetazobactam and 5 to ceftazidime-avibactam). No resistance to cefiderocol was detected. During ICU stay, 21 patients (34%) developed secondary bacteremia from other foci and 7 (11%) invasive mycoses. Overall mortality was 49.2%. On the univariate analysis we found statistical significant relationships between mortality and COVID-19 admission, SOFA >= 7 points on the first VAP or the development of secondary bacteremia (Table 1). Conclusion(s): COVID-19 admission, SOFA >= 7 points on the first VAP or other secondary bacteremia were associated with mortality. The 14.3% of respiratory infections were resistant to the new beta-lactamase inhibitor cephalosporins. No resistance to cefiderocol was detected.

Consumption of systemic antibiotics in the Russian Federation in 2017-2021.

Objective. To assess level and the structure of systemic antibiotic consumption in Russia over the period 2017 to 2021. Materials and methods. Data were collected and analysed in compliance with the standard protocol of the World Health Organization Regional Office for Europe by the means of ATC/DDD methodology for J01 group - antibacterials for systemic use. Consumption was calculated for outpatients and inpatients separately as a number of DDDs per 1000 inhabitants per day (DID) for the main classes of antibiotics and the agents with the highest or the most diverse consumption levels for the given period of time, and was based on the data of wholesale purchases and public tenders. Results. Antibiotic consumption in Russia in 2017, 2018, 2019, 2020, and 2021 was 16.6 DID, 14.3 DID, 14.8 DID, 19 DID, and 15.7 DID respectively. Penicillins, macrolides and lincosamides, and quinolones had the highest levels of consumption in outpatients. Prominent increase in outpatient consumption of antibacterials in 2020 was related to three agents: azithromycin, levofloxacin and ceftriaxone. Cephalosporins (mainly III-V generations), quinolones and penicillins had the highest levels of consumption in inpatients. Hospital consumption of meropenem, tigecycline, and vancomycin increased and amikacin and ciprofloxacin decreased over the duration of the study. Conclusions. Levels of systemic antibiotic consumption in Russia for the period 2017 to 2019 were relatively low and consistent with the average means for European Union and European Economic Area countries. The steep increase in consumption in 2020 was probably due to the wide use of antibiotics for the management of COVID-19 patients. The results of the study can be of value for the development of targeted national antibiotic stewardship programs and awareness campaigns as well as for the analysis of trends of emergence and spread of antibiotic resistance.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Antimicrobial resistance and antimicrobial therapy modification during COVID-19 pandemic in large tertiary hospital.

Objective. assessment of the evolution of the microbiological landscape of the hospital for the period of operation in 2020 into a pandemic of a new coronavirus infection in various departments, including intensive care units;change depending on the results of antibacterial therapy regimens. Materials and methods. In a retrospective study, conducted from June to December 2020, in a multidisciplinary hospital working with COVID-19 infection, the resistance of isolated strains of microorganisms was analyzed in patients of different age groups. Resistance was assessed with test points in June and November 2020;depending on this, proposals were made to correct the internal (local) protocols of antimicrobial therapy. Results. The need for frequent and regular microbiological monitoring was confirmed. Further, we understood that the territories of the main and temporary hospital of the City Clinical Hospital No. 40 are heterogeneous and there are obvious differences both in structure and in the level of sensitivity. "In practice, these are two different hospitals". Within the territories, the branches also differ from each other. When analyzing resistance in ICUs, it was revealed that within each hospital in each department, albeit similar in structure and profile of patients, there is a different level of resistance of strains. Conclusions. The structure of sensitivity generally corresponds to the world data, but for some pathogens it differs significantly. Microbiological monitoring should be carried out not only inside the hospital, but also inside the department. The increase in consumption of carbapenems and protected cephalosporins requires a reassessment of the practice of using AMP in any covid hospital, due to the impact on the epidemic situation both in the ICUs and in the hospital.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Novel Coronavirus is the Only Virus Causing Childhood Invasive Diarrhea: A Case Series

Introduction: Typical manifestations of Coronavirus disease 2019 (COVID-19) include respiratory involvement. Gastrointestinal (GI) symptoms have also been reported as early clinical manifestations. The GI involvement can represent with diarrhea, vomiting, and abdominal pain. The present research aimed to identify dysentery as one of the signs of GI involvement in the novel coronavirus infection in children. Case Presentation: We report twelve patients with COVID-19 and dysentery. All these children had positive reverse transcriptionpolymerase chain reaction (RT-PCR) results. None had underlying illnesses or recent travel history. However, all children had contact with a first-degree relative affected by non-digestive COVID-19. In three patients, obvious dysentery was observed, and in the rest, red and white blood cells were evident in the stool exam. Stool exams were negative for bacterial infections, parasites, and the toxin of Clostridium difficile. Abdominal ultrasonography and echocardiographic evaluations to rule out multisystem inflammatory syndrome in children were normal. Supportive treatment, such as zinc supplementation and probiotics, was prescribed. They also received intravenous fluid therapy based on their dehydration percentage. In the end, they were discharged in good general condition without any complications. No GI complications were found in the follow-up series. Conclusion(s): Dysentery in children can be one of the GI manifestations of COVID-19, which is usually self-limiting. It does not require invasive diagnostic measures and antiviral treatments. This symptom is in contrast to other viral infections of the GI tract.Copyright © 2022, Author(s).

Clinico-Epidemiological Profile of Cutaneous Adverse Drug Reactions at Rural Tertiary Care Centre

Background: Cutaneous adverse drug reactions (CADRs), also known as toxidermia, are skin manifestations resulting from systemic drug administration and it constituted 10%-30% among all reported adverse drug reactions (ADRs). These reactions range from mild morbilliform drug rash to much more severe reactions. Material(s) and Method(s): A retrospective observational study was conducted at dermatology outpatient department of rural based tertiary care center for a duration of 03 years from August 2019 to July 2022, a total of 211 patients who had been clinically diagnosed or were suspected to have drug reactions were studied. Result(s): In this observation there was male preponderance (59.72%) and majority of patients were in their 3rd and 4th decade (40.28%) with maculopapular drug rash (33.17%) being most common clinical profile of CADRs, followed by urticaria (23.70%). Less frequently seen CADRs were acneiform eruptions (21), hair Loss (9), photodermatitis (9), generalised pruritus (7), erythroderma (2), pityriasis rosea (2), Stevens Johnson Syndrome-Toxic Epidermal Necrolysis (SJS-TEN) (4), lichenoid drug eruptions (3), Vasculitis (1) and pustular drug eruption (1). The most common group of drugs causing CADRs were antibiotics (40.28%), followed by NSAIDs (28.43%). Conclusion(s): Cutaneous Adverse Drug Reactions (CADRs) are price we pay for the benefits of modern drug therapy;knowledge of these reactions is important for treating physician as prompt recognition and treatment can prove lifesaving.Copyright © 2022 Academic Medicine and Pharmacy

Not all shortness of breath and throat pain is COVID

Case Report: A previously, healthy 18-year-old female presents to a Pediatric Emergency Medicine Department with shortness of breath, fever, and worsening throat and abdominal pain for 3 days. She had a sick contact, a teacher that tested positive for COVID-19 2 weeks prior to presentation. She denies runny/stuffy nose, cough, loss of taste/smell, or rashes/lesions. She denies any significant past medical history including allergies, as well as any history of smoking or any illicit drug use. Upon arrival to the ED, the patient was noted to be tachycardic, hypotensive and febrile. There were no desaturations. Initial physical examination revealed a generally uncomfortable female that was alert and oriented, with noted tenderness over the right anterior neck region, diffuse cervical lymphadenopathy, and painful neck range of motion. Her pharynx was noted to be erythematous without exudates or any unilateral tonsillar swelling. In the ED patient received IV fluid resuscitation and was started on norepinephrine drip, broad spectrum antibiotics. Initial lab workup revealed an anion gap metabolic acidosis, likely secondary to uremia or lactic acidosis from poor perfusion in setting of sepsis and hypovolemia. BUN and creatinine were elevated, likely due to an acute kidney injury (AKI) secondary to hypovolemia. The patient was also found to have an elevated LDH, fibrinogen, and mild elevation of AST. D-Dimer was elevated at 29 000. Covid PCR, Rapid Strep, and respiratory PCR panel were negative. Her chest X-ray (CXR) was negative and ECG showed sinus tachycardia. Given the patient's history of throat and neck pain with shortness of breath, in the setting of a septic picture, a CT scan of neck, chest, abdomen was ordered prior to transferring the patient to the PICU. CT scan of the chest revealed small patches of consolidation with ground glass opacities in the right lung apex, as well as an nearly occlusive, acute thrombosis of the anterior right facial vein. The patient's initial blood cultures grew gram negative bacilli which later were revealed to be Fusobacterium necrophorum. These findings are consistent with Lemierre's syndrome. The patient was treated in the PICU on vasopressors, heparin anticoagulation, and antibiotics for 6 days and discharged with a course of Augmentin. Lemierre's syndrome is an infectious thrombophlebitis of the internal jugular vein. First described by Andre Lemierre in 1936, it begins as a bacterial pharyngitis, generally developing into a peritonsillar abscess or other deep space neck infection with progressive erosion into the internal jugular vein. Diagnostic criteria for Lemierre's syndrome includes radiographically evidence of thrombophlebitis of the internal vein and positive blood cultures. CT and MRI can help make the diagnosis, but are not always required. Treatment is prompt intravenous antibiotics with beta-lactamase penicillins, metronidazole, clindamycin, and third generation cephalosporins. [Figure presented] Copyright © 2023 Southern Society for Clinical Investigation.

The Influence of Obesity on the Evolution of SARS-COV2 Infection

Aim: The issue of body weight has left a deep mark on the COVID-19 pandemic, where this category of patients has been linked to significant increases in morbidity and mortality due to infection. Conversely, due to the restrictions imposed, the pandemic has worsened the situation of overweight people. Our study conducted over a period of one year and five months aims to assess the prevalence of obesity among patients with SARS-COV2 infection in Constanta County. Material(s) and Method(s): This retrospective study included a number of 177 patients hospitalized with the diagnosis of SARS-COV2 infection in the Clinical Hospital of Pneumoftiziology Constanta. Result(s): 2483 of patients confirmed with SARS-COV2 infection were identified in our Department, out of which 302 had a body mass index over 30 kg/m2. We included a random sample of 95 men and 82 women in a database. The average age was 55 years. The most common comorbidities were hypertension (48%), diabetes (13%), and cardiovascular disease (12%). The most common symptoms were fever (67%), cough (58%), dyspnea (37%), and asthenia (29%). The radiological appearance showed the predominance of the moderate form (49%) and the severe form (22%). Antibiotic treatment was based on third-generation cephalosporins (53%), and the evolution was for improvement with a survival rate of 86%. Only one death was reported in our study. Conclusion(s): The body mass index influences the evolution of infected cases. Old age, male gender and associated comorbidities are risk factors for a poorer prognosis and greater complications in patients with SARS-COV2. Copyright © 2021 Andrei Denisa-Gabriela et al., published by Sciendo.

CEFAZOLIN-INDUCED COAGULOPATHY

SESSION TITLE: Critical Thinking SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Cephalosporins have been known to cause hypo-prothrombinemia and prothrombin prolongation (1). The proposed mechanism of this coagulopathy is secondary to a N-methylthiotetrazole side chain interfering with vitamin-k metabolism (1). Current literature supporting the association between cefazolin and hypo-prothombinemia have only been reported through case reports. As cefazolin is a commonly used antibiotic, it is important that healthcare professionals are aware of its potential bleeding risk. We present a case of a 72 year old female with cefazolin-induced hypo-prothrombinemia. CASE PRESENTATION: A malnourished 72-year old female with a past medical history of recent methicillin-susceptible Staphyloccocus aureus (MSSA) bacteremia and COVID-19 pneumonia presented to the emergency department from a skilled nursing facility (SNF) due to shortness of breath. The patient was previously discharged to SNF to complete a 14 day course of IV cefazolin due to her MSSA bacteremia. On admission, vital signs were significant for a respiratory rate of 22 and a pulse oximetry reading of 78% on room air. Laboratory findings were significant for an elevated prothrombin time of >100 seconds, an INR >15, and a D-dimer of 42,344 ng/mlL. A computed tomography angiography (CTA) of the chest revealed a small segmental pulmonary embolus in the right lower lobe of the lung. The patient was started on a heparin drip, placed on a non-rebreather mask, and admitted to the ICU for closer monitoring. Infectious disease was consulted and cefazolin was discontinued. Due to the patient's risk of bleeding her heparin drip was stopped. It was decided not to reverse the patient's coagulopathy with vitamin K as there were no signs of an acute bleed in the setting of an acute pulmonary embolus. The patient was started on nafcillin in place of cefazolin. Four days after discontinuation of cefazolin, the patient's INR had trended down from >15 to 1.6 and she was started on Lovenox 1mg/kg for the treatment of her acute PE. DISCUSSION: Due to the timing of the discontinuation of cefazolin and the correction of the hypo-prothrombinemia, a clear association between the two can be made. It has been proposed that cefazolin's side chain, heterocyclic thiol, 2-methyl-1,3,4-thiadiazole-5-thiol (MTD), causes a similar reaction that other cephalosporins have on the metabolism of Vitamin K (2). This altered Vitamin K metabolism was also likely exacerbated due to the patient's malnourishment and likely depleted vitamin k reserves (2). CONCLUSIONS: Although rare, this case demonstrates the need for clinicians to be aware of the potential bleeding risk associated with cephalosporins and cefazolin in particular. In the future, routine monitoring of PT/INR levels may be recommended when initiating cephalosporins. Reference #1: Park GH, Kim S, Kim MS, Yu YM, Kim GH, Lee JS, Lee E. The Association Between Cephalosporin and Hypoprothrombinemia: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2019 Oct 16;16(20):3937 Reference #2: Shearer, M. J., Bechtold, H., Andrassy, K., Koderisch, J., McCarthy, P. T., Trenk, D., Jähnchen, E., & Ritz, E. (1988). Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status. Journal of clinical pharmacology, 28(1), 88–95 DISCLOSURES: no disclosure on file for John Abernathy;No relevant relationships by Ethan Goldberg No relevant relationships by Renee Miu No relevant relationships by Luis Osorio no disclosure on file for Satesh Saroop;no disclosure on file for Oliver Sevilla;no disclosure on file for Kristen Zubel;

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.

Identification of hACE2-interacting sites in SARS-CoV-2 spike receptor binding domain for antiviral drugs screening.

The key structure of the interface between the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human angiotensin-converting enzyme 2 (hACE2) acts as an essential switch for cell entry by the virus and drugs targets. However, this is largely unknown. Here, we tested three peptides of spike receptor binding domain (RBD) and found that peptide 391-465 aa is the major hACE2-interacting sites in SARS-CoV-2 spike RBD. We then identified essential amino acid residues (403R, 449Y, 454R) of peptide 391-465 aa that were critical for the interaction between the RBD and hACE2. Additionally, a pseudotyped virus containing SARS-CoV-2 spike with individual mutation (R454G, Y449F, R403G, N439I, or N440I) was determined to have very low infectivity compared with the pseudotyped virus containing the wildtype (WT) spike from reference strain Wuhan 1, respectively. Furthermore, we showed the key amino acids had the potential to drug screening. For example, molecular docking (Docking) and infection assay showed that Cephalosporin derivatives can bind with the key amino acids to efficiently block infection of the pseudoviruses with wild type spike or new variants. Moreover, Cefixime inhibited live SARS-CoV-2 infection. These results also provide a novel model for drug screening and support further clinical evaluation and development of Cephalosporin derivatives as novel, safe, and cost-effective drugs for prevention/treatment of SARS-CoV-2.

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.

TIGECYCLINE INDUCED ACUTE PANCREATITIS: A RARE CASE PRESENTATION

CASE: An 81-year-old female with multiple co-morbidities including recent covid-19, presented to the emergency room with shortness of breath. On arrival, she was febrile with a temperature of 101F, pulse 100 beats/min, respiratory rate 14, blood pressure 196/163 and saturating at 75% on 10 L non-rebreather mask. Initial blood work showed WBC 10.9, lactic acid 1.7, BUN/creatinine 27/1.7 (consistent with her baseline), ABG showed pH 7.37, PCO2 49, PO2 88, HCO3 27.9. Chest x-ray demonstrated volume loss in the left hemithorax, airspace disease in the left mid lung and lung base. Due to suspicion for superimposed bacterial pneumonia and positive blood cultures for staphylococcus haemolyticus, she was started on vancomycin and azithromycin. Choice of antibiotics was challenging as she was allergic to penicillin and cephalosporins. During hospitalization, her kidney function deteriorated, vancomycin was substituted with tigecycline on day 3. Day 5 of treatment, she developed multiple episodes of vomiting with epigastric pain, lipase was 4523. Acute pancreatitis was diagnosed with tigecycline presumed to be the inciting agent in the absence of other risk factors such as gall stones, chronic alcohol use, elevated triglycerides, previous known episodes of pancreatitis or any other causative medications. Tigecycline was switched back to vancomycin and she received aggressive IV fluid hydration which also improved her kidney function. Within 48 hours, the patient had improved oxygen saturation, resolution of her abdominal pain, and good oral intake marking significant overall clinical progress. She was discharged on home oxygen and few more days of IV vancomycin for bacteremia. IMPACT/DISCUSSION: Tigecycline is a broad-spectrum glycylcycline antimicrobial agent belonging to the tetracycline class of antibiotics. Tetracyclines have been associated with acute pancreatitis in literature, and concerns about tigecycline-induced acute pancreatitis have been raised over the past decade in post marketing surveys, we described one such case above. Using the Naranjo Adverse Drug reaction probability scale, a score of 6 was achieved, indicating that the patient's pancreatitis was probably related to tigecycline. CONCLUSION: We recommend physicians monitor patients for signs and symptoms of pancreatitis including abdominal pain after initiating treatment with tigecycline. There should be a low threshold for ordering lipase levels and abdominal CT imaging where indicated. If the patient has symptoms concerning for acute pancreatitis, consider stopping tigecycline and switching to a different class of antibiotics immediately.

A RETROSPECTIVE PHARMACOVIGILANCE ANALYSIS AT TERTIARY CARE HOSPITAL: AN OBSERVATIONAL STUDY

Objective: Pharmacovigilance Program of India is a robust program extending from government hospitals to non-government hospital for implementation of policy of safe and rational use of drugs and early signal generation for adverse effects of drugs. Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University is part of this program since 2004. Retrospective analysis of adverse drug reaction (ADR) reported to the adverse drug monitoring center at tertiary Care Hospital. Methods: The study site was Sir Sundar Lal Hospital, Institute of Medical Sciences Banaras Hindu University, Varanasi. The study was performed after the approval of the Institutional Ethics Committee, letter number: Dean/2020/EC/2153. It was a retrospective observational study. Data collected through VigiFlow software in standard IPC Pharmacovigilance Program of India prescribed suspected ADR form, from March 2020 to June 2021 were analyzed. Causality assessment was done using a World Health Organization Uppsala Monitoring Center scale. Results: In the present study, the percentage of male patients affected is 58% and 42% female patient got suffered from adverse drug effects. About 64% of adverse effect are in possible category followed by probable, that is, 36%. The majority of adverse effects are due to antimicrobials, that is, Cephalosporins and Antitubercular group of drugs. About 20.1% adverse events show gastrointestinal symptoms. In the present study, we also observed that 5.17% adverse effects are due to hydroxychloroquine account for gastritis, headache, lethargy, and vomiting which were prescribed as prophylactic drug for COVID-19. Conclusion: Medicine information OPD in every medical college is the need of the hour to increase awareness regarding adverse events. It is important to spread importance of reporting adverse events by spontaneous reporting under Pharmacovigilance Program of India to detect rare and unusual side effects.

EVALUATION OF THE TWO IN-PATIENT HOSPITALS ON POTENTIAL ENVIRONMENTAL HAZARD DURING THE PERIOD OF NEW CORONAVIRUS INFECTION IN THE KHABAROVSK CITY (DECEMBER 2020 — MARCH 2021)

Microbiological monitoring after infectious diseases in the system of epidemiological surveillance implies simultaneous pathogen identification both among patients and in hospital environment. Our aim is to assess potential hospital environmental hazard for the two in-patient infectious disease hospitals of the Khabarovsk city by using bacteriological and epidemiological analysis during new coronavirus disease pandemic. Materials and methods. Bacteriological assessment of nasopharyngeal microflora in 241 patients suffering from community-acquired pneumonia that were hospitalized in the two prevention and treatment facilities of the Khabarovsk city was performed. Sanitary-bacteriological control of hospital environment (428 hospital environment samples and 91 air samples) was carried out in parallel. Bacteriological assessment was performed with classical methods. Identification of isolated bacteriological pathogens and evaluation of drug-resistant strains were carried out by utilizing bacteriological analyzer Vitek 2 Compact. Results. Nine different pathogens (Pseudomonas aeruginosa, Pseudomonas stutzeri, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Pantoea, Enterococcus faecium, Staphylococcus haemolyticus) were isolated in 20 out of 428 samples — 4.7% [2.7–6.7]. Half of isolated agents — 2.3% [0.9–3.8] — were represented by drug-resistant isolates (10 out of 20 isolates) including 5 carbapenem-resistant isolates (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae) and 5 isolates with multiple drug resistance (Enterobacter cloacae, Pantoea, Enterococcus faecium, Staphylococcus haemolyticus). Air samples contained pathogenic biological agents found in 6 out of 91 samples — 6.6% [1.5–11.7], and half of them — 3.3% [0.6–7.9] — were identified as drug-resistant variants, including S. aureus и S. haemolyticus. One of the surveyed hospitals was recognized as more hazardous due to microflora isolated from intensive care unit (A. baumannii and P. aeruginosa were resistant to 3rd–4th generation cephalosporins and carbapenems). Conclusion. Revealed circulation of wide range of microorganisms isolated from environment of two in-patient hospitals indicates high risk of healthcare-associated infections formation. Intensive care units can serve as a reservoir of healthcare-associated infections due to high percentage of patients with severe disease cases (“main reservoir” of drug-resistant strains).

EVALUATING THE EFFICIENCY OF SPENDING ON ANTIMICROBIAL THERAPY IN THE PULMONOLOGY DEPARTMENT OF A MULTIDISCIPLINARY HOSPITAL IN A PANDEMIC SETTING

Introduction: Antimicrobial resistance is recognized as one of the top 10 threats to public health.Due to recent circumstanceswith the 2019 Covid pandemic worldwide, the urgency of monitoring antibiotic consumption and rational use of medications has increased. According to WHO recommendations, countries should aim to increase the proportion of Access group antibiotics consumption to 60% and higher in AWaRe classification system (Access,Watch and Reserve). The ABC/VEN analysis (80%, 15%, 5% of spending) is the simplest and most relevant method for evaluating the effectiveness of antibiotic therapy expenditures. Objectives: Evaluating the cost-effectiveness of antibiotic therapy in the Department of Pulmonology. Methods: ABC/VEN analysis was performed with data on antibiotic costs in the pulmonology department (30 beds) of a multidisciplinary regional hospital (844 beds in total) with 1 full-time clinical pharmacologist for no clinical pharmacy or pharmacology service. To analyze antibiotic consumption patterns according to the AWaRe 2021 classification, we used data on the number of antibiotics procured. Results: The results of the antibiotics spending analysis from 2019-2021 showed that all antibiotics from the most costly group A (80% of total spending) are in the Watch group (J01DH Carbapenems - Ertapenem, Doripenem, Meropenem;J01MA Fluoroquinolones - Levofloxacin;J01DD Third-generation-cephalosporins - Ceftazidime, Ceftriaxone and J01DE Fourth-generation-cephalosporins: Cefepime). Meanwhile, there has been an increase in the share of spending on the most consumed group of antibiotics, J01DH Carbapenems, from 42.9% in 2019 to 62.8% by 2021. On the contrary, there is downward trend in spending on the third-generation-cephalosporins which was 35.6% in 2019 and only 6.7% by 2021. Assessment of antibiotic prescription patterns in the pulmonology department based on classification AWaRe 2021 and WHO Model List of Essential Medicines (EML) 2021 (22nd edition) revealed a negative trend in the use of the most costly group (A) of antibiotics with a low level of evidence of efficiency or safety in pulmonology: Doripenem, Ertapenem, Levofloxacin, Cefepime. However, there is a positive result in the work of the clinical pharmacology service - the drugs mentioned above were moved into group B (medium-cost) by 2021, except for Cefepim, which was not purchased at all. Conclusion: Despite the positive trend in antibiotic consumption patterns (transfer of antibiotics with efficiency proof from gr A to gr B), current antibiotic therapy in the pulmonology department needs comprehensive optimization of approach to rational antibiotic use, strengthening pharmaceutical care by implementing a clinical pharmacy service that will conduct regular systematic evaluation and contribute to the pharmacoeconomic expediency of antibiotic therapy. Suchmeasures lead to an improvement of the quality of medical care for the population and reduce the cost of this nosology, which proves that there is a need for a comprehensive detailed analysis.

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.

Improving Antimicrobial Stewardship through Allergy Testing Referrals

Background. Penicillins and cephalosporins (PCN/CEPH) are considered firstline antibiotics for numerous infections for their efficacy, tolerability, and cost effectiveness. Unfortunately, their use may be precluded in approximately 10% of the general adult population who self-report 'allergy'. As a result, suboptimal antimicrobials are substituted which may increase toxicities, length of hospitalizations, and antimicrobial resistance with subsequent expense and morbidity. Multiple organizations endorse beta-lactam allergy skin testing (BLAST) as an essential component of antimicrobial stewardship programs.In an attempt to better describe this patient population as well as to protocolize and improve rates of referral to allergy/immunology clinic, a quality initiative was undertaken at our institution. Methods. Adult inpatients for whom an infectious disease consult was placed over a 6-month period were chart-reviewed for PCN/CEPH allergy. Inappropriately charted allergies were reconciled and patients were recommended referral to allergy/immunology for formal evaluation with BLAST when appropriate. Referrals were placed for agreeable patients who were then evaluated for appropriateness through history and then scheduled for BLAST. Patients who tolerated oral exposures without adverse effects had the allergy removed from their chart and were educated. Results. 322 patients met inclusion criteria for allergy referral. Of those, 103 agreed to further evaluation, and referrals were placed for 100%. Unfortunately, 7 patients died before referrals could be completed, and 88 referred patients did not complete BLAST for other reasons. In total 8 patients completed BLAST, and allergy was de-labeled in 75% (N= 6) of those cases. Conclusion. Our data indicated similar prevalence of reported PCN/CEPH allergy between our institution and the general population. We achieved our aim of improving allergy referral rates among this population, however there was a high rate of attrition in the transitions of care. Qualitative review of selected patients highlights common thematic barriers including the COVID-19 pandemic, fiscal concerns, and acuity of condition. Future directions should include BLAST at the point of care or making referrals from the primary care setting.