Pulmonary infections in cancer patients

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

Distribution and drug resistance analysis of pathogenic bacteria in a hospital blood culture, 2018-2022

Objective: To analyze the distribution and drug resistance of pathogenic bacteria in blood culture specimens of patients with bloodstream infections before and after COVID-19 (2018-2019 and 2020-2021), and to provide scientific basis and reference for rational treatment and effective control of bloodstream infections in the post-epidemic period. Methods: Blood culture specimens were collected from patients in Zhongnan Hospital of Wuhan University in the two years before and after the COVID-19 outbreak (2018-2021). The Automated Blood Culture Systems were used to perform blood culture on blood specimens sent for clinical inspection, and the Vitek MS automatic bacterial identification mass spectrometer was used for strain identification and the Vitek 2 automatic bacterial drug susceptibility analyzer was used for drug susceptibility testing and drug resistance analysis. Results: Blood culture specimens were performed on 28 736 patients with suspected bloodstream infection submitted for inspection from January 2018 to December 2019, and a total of 2 181 strains of pathogenic bacteria were detected after removing duplicate strains, with a positive rate of 7.69%, including 1 046 strains of Gram-negative bacteria, accounting for 47.96%. From January 2020 to December 2021, blood culture specimens from 26 083 patients with suspected bloodstream infection were submitted for inspection, and a total of 2 111 strains of pathogenic bacteria were detected after excluding duplicate strains, with a positive rate of 8.09%, including 1 000 strains of Gram-negative bacteria accounted for 47.37%. The drug resistance of Klebsiella pneumoniae was relatively serious, and the sensitivity rate to ertapenem, polymyxin B and tigecycline was more than 90%. The main non-fermentative bacteria Acinetobacter baumannii was more than 50% sensitive to piperacillin/tazobactam, amikacin and polymyxin B. The sensitivity rates of Pseudomonas aeruginosa to piperacillin/tazobactam, ceftazidime, cefepime, amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, piperacillin and meropenem were more than 50%. Conclusions: In the two years before and after COVID-19, there are many types of pathogenic bacteria in bloodstream infection, but the distribution do not differ significantly. The pathogens of bloodstream infection are mainly distributed in ICU, hepatobiliary research institute, and nephrology department. Among them, Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii are the main ones, and different pathogens showed great differences in drug resistance.

Out-Patient Antimicrobial Therapy Unit in Universiti Malaya: The Experience of a Single Tertiary Centre in the Klang Valley

Intro: The Out-Patient Parenteral Antimicrobial Therapy (OPAT) is a form of Antimicrobial Stewardship that is now widely-practise throughout the world. However, in Malaysia, this has just only begun to take root and the OPAT in Universiti Malaya (UM) has only just begin operating on 2 August, 2018. The OPAT in Universiti Malaya has been operating for 4 years and is a collaboration between the General Medical Unit and the Infectious Control Unit. Method(s): This was a longitudinal study of all the patients that has been admitted to the OPAT since the start of the service. For each patient the starting and ending date in OPAT, anitbiotic used, the diagnosis, the referring unit, and any problems were recorded. Finding(s): The total patient-days of antibiotics served in the OPAT was 4978, with a mean duration of 66.37 days per patient and a median of 31 days. The majority of cases was referred from the medical department with 41 cases (54.67%) followed by Surgery with 22 cases (29.33%). Ertapenem was the most common antimicrobial served with 39 patients on it (52%) and ceftriaxone was second with 8 patients served (10.67%). All antibiotics have been agreed upon by the Infectious Disease Unit. In our study, 2 patients in OPAT has died but the rest none of them were admitted for hospital associated infection. Discussion(s): We found that OPAT on average save at least ten beds per day in the hospital. The patients are happy because they do not need to be warded in hospital to receive their antimicrobials. However, we faced limitations in recruitment of patients to the OPAT during the COVID-19 pandemic, staff shortages, the lack of infusion pumps for serving multidose antimicrobials, and bureacratic red-tape. Conclusion(s): OPAT was useful in reducing bed occupancy rate and hospital associated infection. Patients also are happy with the service.Copyright © 2023

Carbapenem Heteroresistance Mdr Enterobacter Cloacae in a Post-Covid-19 Obese Patient: An Antibiotic Susceptibility Conversion

Intro: Background: Obesity affects drug delivery and clearance owing to the patient's altered pharmacokinetics. In treating infection, this presents as a conundrum antibiotic dosing to achieve optimal antibiotic concentration at the same time avoiding drug toxicity. Particularly in the case of antimicrobial agents, underdosing may lead to antibiotic resistance. Method(s): Case description: We report a case of a morbidly obese (BMI=58) COVID-19 patient infected with carbapenem-sensitive multi-drug resistant (MDR) Enterobacter cloacae bacteremia, treated with ertapenem 1g twice daily and intravenous polymyxin E 9MU stat and 4.5MU twice daily for MDR Acinetobacter baumanii co-infection. He had infected huge grade IV sacral sore one month later in which intraoperative tissue culture grew phenotypically heterogeneous colonies of MDR Enterobacter cloacae with carbapenem-sensitive and carbapenem-intermediate-resistant non-carbapenemase producing colonies. He responded well clinically and biochemically with an increased dose of intravenous ciprofloxacin 800mg BD based on his actual body weight. He was discharged with oral ciprofloxacin 750mg BD for a total of six weeks. Finding(s): Discussion: Obesity is a public health crisis that has reached epidemic proportions. Obesity affects the volume distribution and renal clearance of many drugs including antibiotics. Obese patients are shown to have higher drug clearance than normal-weighted patients resulting in inadequate systemic exposure. This puts patients at risk of developing antibiotic resistant organisms. Our patient, weighing 162kg was given three different beta-lactam antibiotics to treat his infection including ertapenem in which a standard adult dose was given without body weight consideration. Possible underdosing contributed to the conversion of carbapenem susceptibility from sensitive to resistant strain. Conclusion(s): Obese individuals may need a larger ertapenem dose than their non-obese counterparts. Clinical and laboratory assessment may help in monitoring treatment response in this group of patients.Copyright © 2023

Revealing Potential Binding Affinity of FDA Approved Therapeutics Targeting Main Protease (3CLpro) in Impairing Novel Coronavirus (SARS-CoV-2) Replication that Causes COVID-19

Background: Spread of COVID-19 attains a crucial transition in reveling its pandemic across the boundaries. In combating the infection caused by SARS-CoV-2, there is a spectrum of ideal strategies that have been adopted globally, of which repurposing of approved drugs considerably having high clinical relevance. 3-chymotrypsin-like protease (3CL pro) is considered to be the potential target for the researchers as it is highly essential for cleavage of polyprotein to get 16 nonstructural proteins (called nsp1-nsp16). These proteins are highly essential for viral replication and hence become a primary target for enzyme inhibitors. 3CL pro, having a structural projectile helical chain with biologically active site involved in processing viral polyproteins that are evolved from RNA genome translation. Objective(s): The major objective of the present investigation is to evaluate the enzyme inhibition potential of FDA approved therapeutic leads in targeting 3CLpro that medicates the viral replication. Method(s): Docking calculations were carried out for an array of FDA approved molecules which leads to a notable few molecules such as Emtricitabine, Oseltamivir, Ganciclovir, Chloroquine, Baricitinib, Favipiravir, Lopinavir, Ritonavir, Remdesivir, Ribavirin, Tenofovir, Umifenovir, Carbapenam, Ertap-enem and Imipenam which have both specificity and selectivity in terms of binding efficiency against 3CL proenzyme. Result(s): A combinatorial evaluation employing in-silico screening shows a major lead for remdesivir which possesses a substantial affinity to 3CL pro binding on core amino acid residues, such as Leu 27, His 41, Gly 143, Cys 145, His 164, Met 165, Glu 166, Pro 168 and His 172 which share the biological significance in mediating enzymatic action. Results of docking simulation by Autodock over a host of FDA approved molecules show high degree of selectivity and specificity in the increasing order of binding capacity;Remdesivir> Ertapenem> Imipenam> Tenofovir> Umifenovir> Chloroquine> Lopinavir> Ritonavir> Emtricitabine> Ganciclovir> Baricitinib> Ribavirin>Oseltamivir>Favipiravir> Carbapenam. Conclusion(s): Till date, there is no known cure attained for treating COVID-19 infection. In conclusion, lead molecules from already approved sources provoke promising potential which grabs the attention of the clinicians in availing potential therapeutic candidate as a drug of choice in the clinical management of COVID-19 time-dependently.Copyright © 2020 Bentham Science Publishers.

A HARD PILL TO SWALLOW

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Epiglottitis is an inflammation of the epiglottis which can be life-threatening in the absence of prompt intervention. Although primarily a pediatric condition, streptococcus pneumonia has been identified as a common pathogen in adults. SARS-CoV 2 has been known to affect a multitude of systems including the upper respiratory tract, but rarely the epiglottis. CASE PRESENTATION: A 66-year-old female with a past history of hypertension, and hypothyroidism presented with acute onset pharyngodynia and dysphagia with a feeling of throat closing up due to swelling and difficulty speaking. She had a recent COVID-19 diagnosis and was doing well except for mild fatigue. Upon presentation, she was hemodynamically stable. Physical exam revealed posterior pharyngeal edema without any exudate, mildly edematous uvula, and no stridor. Laboratory data was pristine except for elevated inflammatory markers. Rapid streptococcal test and MRSA swab were negative. Sputum culture showed usual respiratory flora and blood cultures were negative. A neck CT showed diffuse edema without any evidence of abscess. Laryngoscopy performed by the ENT surgeon revealed diffuse edema including epiglottitis. Emergent intubation revealed supra and epiglottis edema sparing the vocal cords. The patient was given Decadron and Benadryl to help with the edema along with clindamycin and subsequently transferred to ICU for further care. She was treated with Ceftriaxone for 7 days due to a chest X-ray finding of pneumonia. As for COVID 19 treatment, she received a course of Remdesivir and Decadron. Decadron was given at an increased interval to reduce edema around the epiglottis. Her ICU course was complicated with hypotension requiring intermittent vasopressor support, and acute kidney injury from ischemic acute tubular necrosis which slowly improved. Repeat CT chest showed bibasilar consolidations with peripheral ground-glass opacities. In view of hospital-acquired pneumonia, she was started on Ertapenem. Her clinical condition improved and she was successfully extubated. She was shifted to the floors from where she was discharged without any further complications. DISCUSSION: There are only two other reported cases of COVID 19 epiglottitis. The patient's advanced age and obesity were non-modifiable risk factors, but the COVID-19 infection played a role. The virus can lead to excessive upregulation of the host inflammatory response through repeat epithelial and endothelial damage leading to a cytokine storm, which may be responsible for this presentation. A great level of attention is to be maintained while attending to these patients given the multitude of systems that can be affected. CONCLUSIONS: COVID-19 is a potential cause of life-threatening acute epiglottitis. Early suspicion and direct visualization of the epiglottis is the key to success for early management. Reference #1: Emberey J, Velala SS, Marshall B, et al. Acute Epiglottitis Due to COVID-19 Infection. Eur J Case Rep Intern Med. 2021;8(3):002280. Published 2021 Mar 3. doi:10.12890/2021_002280 Reference #2: Smith C, Mobarakai O, Sahra S, Twito J, Mobarakai N. Case report: Epiglottitis in the setting of COVID-19. IDCases. 2021;24:e01116. doi: 10.1016/j.idcr.2021.e01116. Epub 2021 Apr 7. PMID: 33842206;PMCID: PMC8025537. DISCLOSURES: No relevant relationships by Arunava Saha

SEVERE THROMBOCYTOPENIA DUE TO ELECTRON-BEAM POLYSULFONE DIALYZER MEMBRANE REACTION MASQUERADING AS CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA

SESSION TITLE: Critical Thinking SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: We describe a case of severe thrombocytopenia due to reaction with an electron-beam sterilized polysulfone (PS) membrane in a patient with a previous diagnosis of reported chronic immune thrombocytopenic purpura (ITP). This phenomenon has been previously described but is rarely reported. Electron-beam (e-beam) sterilized PS membranes are classically more biocompatible than cellulose-based membranes but adverse reactions may occur as demonstrated in our case. CASE PRESENTATION: An 84-year-old woman with ESRD on hemodialysis (HD) and reported chronic ITP refractory to glucocorticoids with severe thrombocytopenia at baseline presented for evaluation of chest pain. She was incidentally found to have severe thrombocytopenia and treated with high dose glucocorticoids with minimal improvement in her thrombocytopenia and transitioned to chronic glucocorticoid taper. She had a severe chronic thrombocytopenia despite glucocorticoids which was suspected to be chronic ITP and diagnosed after initiation of outpatient HD. HD was held the first few days of her admission. She was found to have multifocal pneumonia due to SARS-CoV-2 infection. She developed progressive hypoxemic respiratory failure requiring intubation with sepsis treated with vancomycin & piperacillin-tazobactam. BAL revealed ESBL Escherichia coli & transitioned to ertapenem. She developed recurrent thrombocytopenia following HD and her PLT would improve between HD sessions. Evaluation of usual culprits of thrombocytopenia was unrevealing. Reaction to the PS membrane was suspected and a cellulose-based dialyzer membrane was used instead for subsequent sessions of HD with recovery of the platelet counts to normal. The remainder of her course was significant for tracheostomy with ventilator dependence and surrogate pursued compassionate care. DISCUSSION: We describe an interesting case of severe thrombocytopenia due to PS membrane reaction which was previously labeled as chronic ITP. Usual culprits such as pseudothrombocytopenia, HIT, HIV, HCV, hypersplenism, alcohol use, nutritional deficiencies, and rheumatologic disease were excluded. Synthetic membranes like PS-membranes are traditionally regarded as more biocompatible but filter reactions are described [1]. It is hypothesized that e-beam radiation may affect dialyzer membrane integrity or structure, or produce intermediary products which may cause platelet activation, aggregation, and adsorption, and therefore thrombocytopenia [2]. There is a high prevalence of thrombocytopenia among critically ill patients undergoing HD [3]. CONCLUSIONS: Thrombocytopenia due to PS dialyzer membrane is a rarely reported phenomenon and may be underrecognized in critically ill patients. This entity should be considered in the differential diagnosis of patients undergoing HD who develop thrombocytopenia. Early recognition may reduce incidence of bleeding and need for blood products in these patients. Reference #1: Golli-Bennour EE, Kouidhi B, Dey M et al. Cytotoxic effects exerted by polyarylsulfone dialyser membranes depend on different sterilization processes. Int Urol Nephrol 2011;43: 483–490. Reference #2: Batalini F, Aleixo GF, Maoz A, Sarosiek S. Haemodialysis-associated thrombocytopenia: interactions among the immune system, membranes and sterilisation methods. BMJ Case Rep. 2019 Sep 4;12(9):e229594. doi: 10.1136/bcr-2019-229594. PMID: 31488440;PMCID: PMC6731774. Reference #3: Griffin BR, Jovanovich A, You Z, Palevsky P, Faubel S, Jalal D. Effects of Baseline Thrombocytopenia and Platelet Decrease Following Renal Replacement Therapy Initiation in Patients With Severe Acute Kidney Injury. Crit Care Med. 2019;47(4):e325-e331. doi:10.1097/CCM.0000000000003598 DISCLOSURES: No relevant relationships by Adefemi Adeyemo No relevant relationships by Zachary Chandler No relevant relationships by Bijal Patel No relevant relationships by Vandana Seeram

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.

Visceral Mycotic Aneurysm: Superior Mesenteric Artery Aneurysm Caused by K. pneumoniae

We herein report a rare case of mycotic aneurysm of the superior mesenteric artery caused by Klebsiella pneumoniae. A 66-year-old man, a known case of hypertension and aorto-oesophageal fistula with stented aorta in 2010 and 2018, presented to the emergency department multiple times over 2 months with severe postprandial abdominal pain associated with vomiting and fever. On his last presentation, the obtained blood cultures grew ESBL positive K. pneumoniae and a repeated computed tomography (CT) showed a growing aneurysm at the origin of the ileocecal branch of the superior mesenteric artery measuring 17 × 10 mm (the aneurysm was 8 × 7.5 mm in the CT angiography on the previous admission). Extensive workup did not reveal the underlying cause of the mycotic aneurysm, thus we believe the cause to be the infected aortic stent, leading to bacteraemia and vegetations to the mesenteric artery causing the aneurysm. The management plan was placed by a multidisciplinary team consisting of vascular surgeons and infectious disease specialists along with review from a dietician to evaluate the patient's nutritional status. The patient was started on total parenteral nutrition due to his postprandial pain and on antibiotic therapy according to the infectious disease team's recommendation. He underwent surgical resection of the mycotic aneurysm, which showed a thrombosed aneurysm in the jejunoileal mesenteric area. The histopathology of the resected tissue demonstrated inflammatory aneurysm of the mesenteric artery. Following the surgery, the patient continued his antibiotic therapy and was discharged on the 13th post-operative day with follow-up appointments in the vascular surgery and infectious disease clinic.

POS-497 SUCCESSFUL BARIATRIC SURGERY FOLLOWING SECOND RENAL TRANSPLNATATION. AND OTHER COMPLICATIONS DURING THE JOURNEY

Introduction: Obesity is highly prevalent among patients with renal transplants. It is associated with increased risk of overall mortality, obesity-related complications such as diabetes, increased renal graft loss rates and shortened graft survival. Roux en Y gastric bypass in contrast to other non malabsorptive procedures, may affect the pharmacokinetics of certain drugs, which is of particular importance for immunosuppressant drugs required by patients post-transplant to avoid graft rejection. Methods: 43-year-old female known case of IgA nephropathy biopsy proven in 2000, progressed to end stage renal disease (ESRD) and was initiated on hemodialysis. She underwent live unrelated renal transplantation. Creatinine was 79 micromole/L and eGFR 85ml/min/1.73 m2. Her maintenance immunosuppression included azathioprine 50 mg daily, cyclosporine 75 mg bid and prednisolone 5 mg daily. She had two successful pregnancies post renal transplantations. She developed post renal transplant diabetes in 2013 and uncontrolled hypertension. She had persistent microscopic hematuria. Her creatinine peaked up to 275 micromol/L, her allograft kidney biopsy showed histopathologic features for mild acute T-cell mediated rejection (probably modified slightly by anti-rejection treatment). Grade 1A by Banff working grading. C4d stain is negative with background of focal proliferative and sclerosing glomerulonephritis with associated IgA deposits, consistent with IgA nephropathy ("M1, E1, S1, T0" Oxford classification). Her rejection was treated with pulse IV steroids, azathioprine was changed to mycophenolate and dose of cyclosporine was increased to 100 mg bid. Her creatinine came down to 105 micromol/L. Her post transplantation course involved purpuric rash, joint pain, abdominal pain, h/o HSP biopsy proven with elevated ESR and CRP most likely this is HSP again associated with medication exposure, possible the fibrate. Results: She lost follow up in our clinic and showed up after 5 years with uremic symptoms and creatinine of 1,063micromol/L and was initiated on hemodialysis in 2019. She had second live unrelated renal transplantation, she received 3 sessions of plasma exchange and IVIG prior to transplantation and was maintained on tacrolimus, mycophenolate and prednisolone. Her creatinine was 88 micromol/L. She had Laparoscopic sleeve gastrectomy and Dermo lipectomy of abdominal wall 2 months following her transplantation and lost 22 kgs since then, her BMI was 32 kg/m2 dropped to 24 kg/m2 in 6 months duration. The patient suffered from recurrent multi drug resistant E.Coli urinary tract infection treated with IV ertapenem and continued on trimethoprim sulpha- methoxazole prophylaxis for 6 months. She is still using insulin in smaller doses and her blood sugar is within acceptable ranges. She recently suffered from covid 19 pneumonia requiring home quarantine during which her creatinine went up to 106 micromol/L but settled down to baseline of 88 micromol/L during further follow up. Conclusions: Limited evidence suggests that bariatric surgery is safe and feasible for selected obese patients post-renal transplant. It is associated with good, if variable, short-term excess weight loss and resolution of co-morbidities. More studies should address long term complications in renal trnasplant patient population. No conflict of interest