Broad-spectrum Antimicrobials Research Articles

De-escalation antibiotic therapy alleviates organ injury through modulation of NETs formation during sepsis

Empiric broad-spectrum antimicrobials therapy is suggested to be started immediately for sepsis patients. Empiric antimicrobial therapy should be narrowed once pathogen identification and sensitivities are established. However, the detailed mechanisms of de-escalation strategy are still unclear. Here we hypothesized neutrophil extracellular traps (NETs) played an essential role and de-escalation strategy might alleviate organs injury through regulation of NETs formation in sepsis. We evaluated the effect of imipenem and ceftriaxone on NETs formation in vitro and examined the role of reactive oxygen species (ROS). Next, we designed de-escalation and escalation strategy in cecum ligation and puncture (CLP) models. Organ injury, inflammatory cytokines, NETs levels were compared and evaluated. In CLP models, de-escalation therapy resulted in an increased serum MPO-DNA level during the early stage and decreased MPO-DNA level during late stage, which exerted the reverse effects in escalation therapy. Inflammatory response and organ injury exacerbated when eliminated NETs with DNAse I during the early stage of sepsis (p < 0.01). Histopathological analysis showed decreased injury in lung, liver, and intestine in de-escalation therapy compared with escalation therapy (p < 0.01). De-escalation therapy results in the highest 6-day survival rate compared with the control group (p < 0.01), however, no significant difference was found between de-escalation and escalation group (p = 0.051). The in vitro study showed that the imipenem could promote, while the ceftriaxone could inhibit the formation of NETs in PMA-activated PMNs through a ROS-dependent manner. We firstly demonstrate that de-escalation, not escalation, therapy reduces organ injury, decreases inflammatory response by promoting NETs formation in the early stage, and inhibiting NETs formation in the late stage of sepsis.

Use of Antimicrobials in a French Veterinary Teaching Hospital: A Retrospective Study.

Antibiotic resistance has become a major concern for not only human health, but also for animal health. To preserve the efficacy of antibiotics, it has become essential to establish measures to regulate the prescription of antibiotics to ensure their prudent use. In France, these measures have been translated into regulations for animal health since 2015, with the publication of three important regulatory texts. The results obtained on a national scale in terms of reducing the use of antibiotics have been satisfactory. The aim of our study was to evaluate the differences related to the prescription of antimicrobials at the veterinary teaching hospital of the Veterinary School of Lyon (CHUV) before and after the implementation of French regulations. Prescriptions and consumption of antimicrobials were examined, along with bacteriological analyses, for the period of 2014–2020, for companion animals and horses. The most frequently prescribed compounds were broad-spectrum antimicrobials, including penicillins with β-lactamase inhibitors, as well as first-generation cephalosporins tetracyclines and sulfamides. The prescription and consumption of critically important antibiotics (CIA) strongly decreased during the study period, with an increase of bacteriological analyses. This study shows the interest of having computerized tools to monitor the use of antimicrobials to implement corrective measures if needed.

Myometrial Abscess in the Noninstrumented Uterus

A 67-year-old female with pelvic pain and leukocytosis had imaging demonstrating a 3.2 × 2.3 cm ring-enhancing lesion suspicious for a myometrial abscess (Fig. 1). She was in remission from mantle cell lymphoma after total body radiation and chemotherapy. Initially vitally stable and afebrile, she eventually developed sepsis despite conservative management with broad-spectrum antimicrobials. Exploratory laparoscopy demonstrated diffuse abscesses and abdominopelvic adhesions (Fig. 2). Intraoperative finding of the ruptured cornual abscess (Fig.

Exposure to Anti-Anaerobic Antimicrobials Around Hematopoietic Cell Transplant (HCT) Is Associated with Poor Outcomes in Pediatric Patients

BackgroundSurvival rates in pediatric hematopoietic cell transplant (HCT) have improved over the last several decades. However, the factors that influence suboptimal outcomes continue to be less well understood. Low diversity of the gut microbiota and dysbiosis are known to be associated with poor outcomes after HCT. Exposure to broad-spectrum antibiotics, particularly those with anti-anaerobic coverage, during the course of HCT can induce both loss of gut microbial diversity and worsen dysbiosis. We explored the relationship of exposure to antibiotics with outcomes after HCT among pediatric patients, specifically with respect to the development of acute graft versus host disease (aGVHD).MethodsWe performed a single institution, retrospective cohort study to evaluate the association of peri-HCT antibiotic exposures with post-HCT outcomes. All patients who underwent their first transplant between 2008-2019 at our institution were included in this study. Patient, disease, HCT, and antibiotic exposure related data were abstracted from patient medical charts. The primary independent variable of interest was exposure to antibiotics for at least 48 hours at any time point from the start of conditioning and up to 100 days after the graft infusion. Antibiotics were further classified based on anti-anaerobic activity. Antibiotic exposure was censored 7 days prior to aGVHD diagnosis. Descriptive statistics are provided. Overall survival (OS) and event-free survival (EFS) curves/functions were estimated by the Kaplan-Meier method, and compared using the log-rank test. Cumulative incidence curve/function of aGVHD (any organ), gastrointestinal aGVHD, relapse and non-relapse mortality (NRM) was estimated by the Kalbafleisch-Prentice method accounting for competing risks and compared by Gray's test. Statistical analyses were performed with SAS version 9.4ResultsA total of 492 patients underwent their first HCT at our center during the study time period. The majority of patients underwent HCT for an underlying malignant disorder (n=408, 83%). A total of 174 patients died (35%); causes of death included GVHD (n=7, 4%), infection (n=31, 17.8%), organ dysfunction (n=34, 19.5%), or relapse (n=102, 58.6%). The cohort was then divided into 2 groups based on exposure to anti-anaerobic antibiotics (n=366, 74%), and no exposure to anti-anaerobic antibiotics (n=126, 26%). Overall survival at 2 years was 59% in the group exposed to any anti-anaerobic antibiotics vs. 82% in the unexposed cohort (p<0.01). EFS at 2 years post- transplant was 61% in the group exposed to any anti-anaerobic antibiotics compared to 77% in the non-exposed group (p<0.01). Non-relapse mortality was higher in those receiving anti-anaerobic antimicrobials at 19 vs. 5%. (p<0.01). There was no significant difference in relapse incidence in the two cohorts ( Twenty-three percent (n=116) of all patients were diagnosed with any grade II-IV aGVHD by day +100 with no difference between the 2 groups (p=0.2). Cumulative incidence of grades II-IV gastrointestinal aGVHD was 5.1% (n=27), with a higher incidence in those patients who did not receive anti-anaerobic antimicrobials (11 vs. 3%, p<0.01).DiscussionIn our cohort, exposure to anti-anaerobic antimicrobials in the peri-transplant setting was associated with increased mortality. The OS and EFS were significantly lower among those exposed to even short periods of anti-anaerobic antimicrobials. No corresponding increase in relapse was seen in those who received anti-anaerobic antibiotics. Infection and organ dysfunction were the leading causes of death in both exposed and unexposed cohorts. The decreased survival does not appear to be driven by aGVHD, as the overall incidence of aGVHD was not significantly different between the two groups. The exact cause-effect relationship between antibiotic exposure and outcomes after HCT in pediatric patients remains to be elucidated. Further studies should focus on the interaction of the nascent immune system, recipient microbiota, and exposure to broad-spectrum antimicrobials, particularly as they relate to the development of GVHD. [Display omitted] DisclosuresSharma: Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution; Spotlight Therapeutics: Consultancy; Vindico Medical Education: Honoraria; CRISPR Therapeutics: Other, Research Funding; Medexus Inc: Consultancy; Novartis: Other: Salary support paid to institution.

Antimicrobial property of recombinant Lactolisterin BU in vitro and its initial application in pork refrigerated storage

Lactolisterin BU is a novel bacteriocin identified from Lactococcus lactis in 2017. It exhibits antimicrobial activity against food spoilage and foodborne pathogens. In this study, Lactolisterin BU was expressed in Pichia pastoris (P.pastoris) and isolated from the supernatant of yeast culture for the first time. It was found to exhibit a broad antimicrobial spectrum and rapid bactericidal activity against foodborne bacterial pathogens, both gram-positive and gram-negative ones, with minimum inhibition concentrations ranging within 10–60 μg/mL. The recombinant Lactolisterin BU (rLactolisterin BU) also had an antioxidant effect and was resistant to heating, acid–base, and high-dose-saline treatments and barely had any hemolytic activity or cytotoxicity. Moreover, rLactolisterin BU effectively suppressed the growth of bacterial pathogens; suppressed the increases in pH, total volatile basic nitrogen (TVB-N), and thiobarbituric acid reactive substances (TBARS) of pork samples; and maintained a high quality of fresh pork during storage at 4 ℃. Furthermore, rLactolisterin BU effectively inhibited the growth of three kinds of bacteria in a pork-spoilage model. Taken together, rLactolisterin BU could be a promising preservative for food storage.

Tandem Repeat of a Short Human Chemerin-Derived Peptide and Its Nontoxic d-Lysine-Containing Enantiomer Display Broad-Spectrum Antimicrobial and Antitubercular Activities.

To design novel antimicrobial peptides by utilizing the sequence of the human host defense protein, chemerin, a seven-residue amphipathic stretch located in the amino acid region, 109-115, was identified, which possesses the highest density of hydrophobic and positively charged residues. Although this 7-mer peptide was inactive toward microorganisms, its 14-mer tandem repeat (Chem-KVL) was highly active against different bacteria including methicillin-resistant Staphylococcus aureus, a multidrug-resistant Staphylococcus aureus strain, and slow- and fast-growing mycobacterial species. The selective enantiomeric substitutions of its two l-lysine residues were attempted to confer cell selectivity and proteolytic stability to Chem-KVL. Chem-8dK with a d-lysine replacement in its middle (eighth position) showed the lowest hemolytic activity against human red blood cells among Chem-KVL analogues and maintained high antimicrobial properties. Chem-8dK showed in vivo efficacy against Pseudomonas aeruginosa infection in BALB/c mice and inhibited the development of resistance in this microorganism up to 30 serial passages and growth of intracellular mycobacteria in THP-1 cells.

Current approaches to the treatment of rhinosinusitis

Relevance: despite the available methods and medicines, rhinosinusitis occupies a leading place in the structure of diseases of the upper respiratory tract. Rhinosinusitis can be a consequence of respiratory viral infections, can be an independent nosological unit. In recent years, there has been a protracted course of rhinosinusitis with a long recovery period with chronic inflammation in the paranasal sinuses and nasal cavity. Purpose of the study: to analyze the validity and effectiveness of therapeutic approaches to the treatment of chronic rhinosinusitis using the Polydexa with phenylephrinum nasal spray with phenylephrine Materials and мethods: The study included 121 patients — 61 (50.41 %) women and 60 (49.59 %) men aged 25 to 50 years, a history of chronic rhinosinusitis in the stage of clinical exacerbation at the time of the study. All patients underwent: otorhinolaryngological examination, general clinical and radiological (radiography or computed / magnetic resonance imaging of the paranasal sinuses). Cytological examination of the detachable nasal cavity was carried out to study the calculation of the relative number of neutrophilic granulocytes, macrophages, epithelial cells, lymphocytes. Microbiological examination of the detachable nasal cavity and paranasal sinuses included the study of the qualitative and quantitative composition of pathogenic and opportunistic organisms on the surface of the nasal mucosa. Results: in patients with chronic rhinosinusitis in the stage of clinical exacerbation, an increase in the relative content of inflammatory elements was revealed in the nasal secretion against the background of the prevailing content of pathogenic staphylococci and streptococci. The use of topical preparations containing antibacterial components of a broad antimicrobial spectrum of action, dexamethasone, phenylephrine hydrochloride helps to relieve inflammation on the surface of the mucous membranes of the nasal cavity and paranasal sinuses. Conclusions: a method of treating chronic rhinosinusitis in the stage of clinical exacerbation using a combined preparation for topical application containing neomycin sulfate, polymyxin B sulfate, dexamethasone sodium metasulfobenzoate, phenylephrine hydrochloride has a pronounced anti-inflammatory, decongestant, antibacterial effect

Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia

Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.

Antimicrobial Action of Biocompatible Silver Microspheres and Their Role in the Potential Treatment of Fungal Keratitis.

Silver nanoparticles have drawn considerable attention as excellent antimicrobial agents because of their characteristics, including broad antimicrobial spectrum, durable antimicrobial property, and large specific surface area. However, the toxicity of silver nanoparticles limits the in vivo application in the antimicrobial therapy field. Here, we developed a novel silver-based biomaterial to achieve favorable biocompatibility as well as enhanced antimicrobial activity. Silver microspheres (AgMPs) were synthesized using bovine serum albumin as a template and H2O2 as an activator. Electron microscopy results showed that AgMPs had a honeycombed inner structure with an approximate diameter of 800 nm. The minimum inhibitory concentration results exhibited that AgMPs had effective antimicrobial action against bacteria and fungi when the concentration was greater than 32 and 16 μg/mL, respectively. The cell proliferation results suggested that AgMPs have no influence on corneal epithelial cell growth when the concentration was under 25 μg/mL. The in vivo antifungal therapy experiments demonstrated that 25 μg/mL AgMPs could effectively combat Candida smooth wound infections. Overall, AgMPs exhibited substantial antimicrobial action on fungi in addition to biosafety on corneal epithelial cells at a concentration within 16-25 μg/mL. Our study shows that AgMPs can be used as an ocular surface drop candidate to treat fungal keratitis.

Microbial coinfections and superinfections in critical COVID-19: a Kenyan retrospective cohort analysis

The aim of our study was to outline the burden, risk factors, and outcomes for critical COVID-19 patients with coinfections or superinfections. This was a retrospective descriptive study of adults who were admitted with critical COVID-19 for ≥ 24 hours. Data collected included demographic profiles and other baseline characteristics, laboratory and radiological investigations, medical interventions, and clinical outcomes. Outcomes of interest included the presence or absence of coinfections or superinfections, and in-hospital mortality. Differences between those with and without coinfections or superinfections were compared for statistical significance. In total, 321 patient records were reviewed. Baseline characteristics included a median age (IQR) of 61.4 (51.4-72.9) years, and a predominance of male (71.3%) and African/black (66.4%) patients. Death occurred in 132 (44.1%) patients, with a significant difference noted between those with added infections (58.2%) and those with none (36.6%) (p=0.002, odds ratio (OR)=2.41). One patient was coinfected with pulmonary tuberculosis. Approximately two-thirds of patients received broad-spectrum antimicrobial therapy. Added infections in critically ill COVID-19 patients were relatively uncommon but, where present, were associated with higher mortality. Empiric use of broad-spectrum antimicrobials was common, and may have led to the selection of multidrug-resistant organisms. More robust local data on antimicrobial susceptibility patterns may help in appropriate antibiotic selection, in order to improve outcomes without driving up rates of drug-resistant pathogens.

Composition and Activity Analysis of Supercritical CO 2 Extract from Zanthoxylum bungeanum Residue

To explore the constituents of Zanthoxylum bungeanum supercritical CO2 extract and its antibacterial and antioxidant effects. The compound composition was analyzed by high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS), its antibacterial activity was analyzed by paper diffusion and double gradient dilution. And the free radical scavenging rate of DPPH and ABTS of the extract was determined to denote antioxidant activity. The results showed that the extract consisted of alkaloids, enols, amides, flavonoids, coumarins and some other components. The relative content of dendromine was the highest, reaching 38.28%. Zanthoxylum bungeanum extract had a broad antimicrobial spectrum. The minimum inhibitory concentration(MIC) against Vibrio parahaemolyticus, Aeromonas hydrophila and Shewanella was of Zanthoxylum bungeanum residue extract were 3.125 mg/mL. Compared with Zanthoxylum bungeanum extract, zanthoxylin and Zanthoxylum bungeanum essential oil, Zanthoxylum bungeanum residue extract had the strongest antioxidant activity, with a clearance rate of 100% of ABTS free fundamentals at 12.5 mg/mL and 91.35% of DPPH free fundamentals at 50 mg/mL. Therefore, the Zanthoxylum bungeanum residue extract had better antibacterial and antioxidant properties. It had a broad development and application potential, could achieve the high-value utilization of Zanthoxylum bungeanum.

HYPERAMMONEMIA IN UNCONTROLLED DIABETES MELLITUS

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Hyperammonemia is a known cause of encephalopathy due to neurotoxic effect. While predominantly attributed to hepatic cirrhosis, other non-cirrhotic causes of hyperammonemia such as malignancy, infection with urea-producing bacteria, and metabolic disorders have also been described. 1 Uncontrolled diabetes mellitus (DM) is a lesser understood cause of sudden or substantial increase in ammonia level. 2 We present a case of a patient with diabetes ketoacidosis (DKA) and encephalopathy in the setting of hyperammonemia. CASE PRESENTATION: The patient is a 57-year-old female with a past medical history of hypertension, type 2 DM, and liver cirrhosis presenting with lethargy and two days of nausea and vomiting in the setting of insulin noncompliance. She was noted to be significantly volume depleted with depressed level of consciousness. The patient received intravenous crystalloid resuscitation, vasopressor support, and broad-spectrum antimicrobials. She developed progressive obtundation, necessitating endotracheal intubation. Laboratory workup was consistent with DKA, with glucose of 979, anion gap >24, HCO3 <10, BHB >2, and pH of 6.74. Her ALT, AST, alkaline phosphatase, and bilirubin were all within normal limits. Additional workup for encephalopathy demonstrated an ammonia level of 1181. CT head showed no evidence of cerebral edema or other intracranial pathology. CT abdomen demonstrated hepatic surface nodularity. In the setting of significantly elevated ammonia, treatment with intravenous insulin infusion and electrolyte repletion for DKA was started. On repeat 3 hours later, the ammonia level decreased to 594 and normalized on day 2. Neurological workup including EEG, MRI and repeat CT head were unremarkable. The patient remained encephalitic precluding extubating until day 9 and was discharged home shortly thereafter. DISCUSSION: Serum ammonia is the result of protein degradation primarily produced in the GI system and removed mostly by the liver and to a lesser extent by the musculature. Hyperammonemia can be caused by a variety of causes including urea cycle disorders, medications, infections, GI bleed, hepatic or renal failure. 2 Undiagnosed hyperammonemia either in acute or chronic setting, can cause irreversible neurological damage. 2 Insulin increases protein synthesis, and insulin deficiency or resistance as it happens in type I and II diabetes mellitus respectively, increases protein catabolism and ammonia production.2–5 The mainstay of treatment in such a setting is aggressive resuscitation and treatment of the DKA. 6–8 CONCLUSIONS: Hyperammonemia due to uncontrolled diabetes mellitus is an under-recognized cause of encephalopathy and should be considered in patients presenting with DKA. REFERENCE #1: Cichoz-Lach H, Michalak A. Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol. 2013;19(1):26-34. doi:10.3748/wjg.v19.i1.26 REFERENCE #2: K G, Dasan.S S, Sheriff D. Hyperammonemia in uncontrolled Type2 Diabetes Mellitus. IOSR Journal of Dental and Medical Sciences. 2016;15:14-19. doi:10.9790/0853-1510031419 REFERENCE #3: Nair KS, Garrow JS, Ford C, Mahler RF, Halliday D. Effect of poor diabetic control and obesity on whole body protein metabolism in man. Diabetologia. 1983;25(5):400-403. doi:10.1007/BF00282518 DISCLOSURES: No relevant relationships by Michael Bonk, source=Web Response No relevant relationships by Seyed Kamran Hejazi Kenari, source=Web Response No relevant relationships by Arman Hemmat, source=Web Response

FEVER OF UNKNOWN ORIGIN IN THE ICU: A CASE OF "GOUTY SEPSIS"

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Gout associated with systemic inflammatory response syndrome is well described but underappreciated in clinical practice. A prospective analysis of cases admitted to the hospital estimate that 4.5% are associated with fever. We present a case of a critically ill patient with persistent fever of unknown origin diagnosed with polyarticular gout two months into his hospitalization. CASE PRESENTATION: A 67-year-old man with a history of gout, atrial fibrillation, and type 2 diabetes was admitted with a left MCA territory stroke and underwent emergent thrombectomy. He had a period of relative neurologic recovery but became encephalopathic necessitating intubation for airway protection. He developed aspiration pneumonia and progressive renal failure requiring dialysis and underwent percutaneous tracheostomy. Over a period of several weeks, he demonstrated recurrent fevers and persistent leukocytosis and received multiple courses of empiric broad spectrum antimicrobials. Serial cultures, evaluation for atypical pathogens, cross-sectional imaging, lumbar puncture, and autoimmune serologies did not identify an etiology, and he was trialed on bromocriptine for presumed central fever. Repeat physical exam elicited multiple swollen and tender joints. Arthrocentesis was performed and notable for monosodium urate crystals. Acute polyarticular gout was diagnosed, and he was started on dexamethasone and later switched over to anakinra (due to uncontrolled hyperglycemia), with resolution of fevers and articular symptoms. After defervescing his neurologic status significantly improved and he was able to successfully liberate from the ventilator. He was ultimately discharged to rehab on hospital day 112. DISCUSSION: Fever is present in up to 70% of ICU patients and when prolonged is associated with increased morbidity and mortality. This case highlights the difficulty of recognizing non-infectious etiologies of fever in the critically ill patient and the potential harms in a missed diagnosis. These include unnecessary antimicrobial exposure, invasive procedures, and prolonged hospital stay. Sedation and encephalopathy often complicate history-taking and diagnosis. Here, careful physical examination led to the diagnosis of an underappreciated manifestation (fever) of a common condition (gout). While the incidence of gout flares in the ICU is unknown, medical stress, dehydration, and diuretics are frequent triggers and common in critically ill patients. Treatment may be challenging as high rates of renal insufficiency can preclude the use of common therapies such as NSAIDs or colchicine, and steroids may potentiate issues with glycemic control. CONCLUSIONS: Polyarticular gout should be routinely considered as a possible cause of fever in the ICU. REFERENCE #1: Schäfer VS. Systemic Inflammatory Polyarticular Gout Syndrome - Description of a Previously Neglected Entity. JSM Arthritis. 2017;2(2): 1024. REFERENCE #2: Circiumaru B, Baldock G, Cohen J. A prospective study of fever in the intensive care unit. Intensive Care Med. 1999. Jul;25(7): 668-73. REFERENCE #3: Raddatz DA, Mahowald ML and Bilka PJ. Acute polyarticular gout. Ann Rheum Dis. 1983;42: 112-117. DISCLOSURES: Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: $5001 - $20000 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: $5001 - $20000 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: 2014-Present Added 04/21/2021 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: 2019-Present Added 04/21/2021 by Jaime Betancourt, source=Web Response, value=Honoraria Advisory Committee Member relationship with Vapotherm, Inc Please note: 2020 Added 04/21/2021 by Jaime Betancourt, source=Web Response, value=Honoraria No relevant relationships by Tracey Liu, source=Web Response No relevant relationships by Scott Oh, source=Web Response No relevant relationships by Jared Wilkinson, source=Web Response

A CASE OF DISSEMINATED INTRAVASCULAR LYMPHOMA PRESENTING AS SEPSIS WITH MULTIORGAN FAILURE

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Intravascular lymphoma (IVL) is a rare subtype of lymphoma proliferating in the lumen causing small vessel occlusion. Antemortem diagnosis is difficult. The majority of cases are diagnosed from autopsy. We report a patient with IVL who presented with sepsis of unknown source complicated by multiorgan failure. CASE PRESENTATION: A 58-year-old male with hypertension and chronic obstructive lung disease presented with fever for 3 weeks and was found to be hypotensive. Laboratory investigation was remarkable for platelet count of 84,000 per microliter, serum creatinine 3 mg/dl, aspartate aminotransferase of 50 units per liter (U/L), total bilirubin of 5 mg/dl, ferritin of 1265 microgram per liter, lactate dehydrogenase of 2051 U/L. Blood, respiratory and urine cultures were negative. CT abdomen and pelvis did not reveal a septisis source. Transthoracic echocardiogram showed a preserve ejection fraction without tamponade. Hemodynamic data from pulmonary artery catheter showed wedge pressure of 14, and mixed venous oxygen saturation of 72. He was diagnosed with septic shock with unknown source and multiorgan failure. He was treated with broad spectrum antimicrobials including Meropenem, Vancomycin and Micafungin. He was started on continuous renal replacement therapy. His clinical course continued to deteriorate. The family decided to withdraw life support. He expired on hospital day 11. An autopsy revealed intravascular large B-cell lymphoma. DISCUSSION: IVL is an extremely rare extranodal lymphoma, predominantly affecting elderly patients. The incidence remains unknown due to its rarity. The clinical presentation is variable, ranging from asymptomatic, constitutional B symptoms to multiorgan failure caused by vessel occlusion. IVL can be diagnosed by the presence of large lymphoma cells within small-to-medium blood vessels. Antemortem diagnosis of IVL is difficult due to lack of pathognomonic features or tumor markers. Symptoms could mimic other more common diseases since the clinical manifestations are heterogeneous which could lead to a delayed or missed diagnosis. IVL is aggressive and usually disseminated at the time of diagnosis. Treatment is systemic chemotherapy. CONCLUSIONS: While IVL is an extremely rare subtype of lymphoma, it should be considered in the differential diagnosis of unexplained multiorgan failure with no other clear cause. The diagnosis of IVL requires a high index of suspicion and should be suspected in patients suggestive relevant clinical findings which may lead to early treatment and better outcomes. REFERENCE #1: Bouzani M et al., "Disseminated intravascular b-cell lymphoma: clinicopathological features and outcome of three cases treated with anthracycline-based immunochemotherapy," The Oncologist, vol. 11, no. 8, pp. 923–928, 2006. REFERENCE #2: Ferreri AJ, Campo E, Seymour JF; International Extranodal Lymphoma Study Group (IELSG). Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the 'cutaneous variant'. Br J Haematol. 2004 Oct;127(2):173-83. REFERENCE #3: Murase T, Yamaguchi M, Suzuki R et al. Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5. Blood. 2007 Jan 15;109(2):478-85. DISCLOSURES: No relevant relationships by Maythawee Bintvihok, source=Web Response No relevant relationships by Parneet Dhaliwal, source=Web Response No relevant relationships by Joseph Guileyardo, source=Web Response No relevant relationships by Adam Hayek, source=Web Response No relevant relationships by Adan (Adam) Mora, source=Web Response

A FATAL CASE OF PULMONARY HEMORRHAGE: RARE MANIFESTATION OF LEPTOSPIROSIS

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Leptospirosis can cause multi-organ failure and adult respiratory distress syndrome. Clinical suspicion is the key to diagnosis. A detailed social history is superior to serum and radiological investigation to prevent mortality. CASE PRESENTATION: A 41-year-old man presented to the hospital with diffuse muscle pain and chills for 3-weeks. He worked as a waste-water worker in New York City. On arrival, he had a temperature of 100.8 F, heart rate 94/min, blood pressure 102/67 mmHg, respiratory rate 21/min. Initial blood tests showed platelet count of 90,000 k/ul, serum creatinine 3.7 mg/dl, BUN 67 mg/dl, ALT 78 u/l, AST 101 u/l and total bilirubin of 6.9 mg/dl. Chest X-ray showed mild diffuse interstitial infiltrates. He was admitted to the medical floor for management of presumed bacterial pneumonia. Broad-spectrum antimicrobials therapy with intravenous vancomycin and cefepime was initiated. One week into inpatient stay, his clinical condition deteriorated with worsening hypoxemia along with worsening renal and liver function tests. Blood cultures, sputum cultures, and COVID-19 PCR tests were negative. CT Chest was performed which showed extensive ground-glass opacities with interstitial thickening in both lungs. He had worsening hypoxemia requiring mechanical ventilation and septic shock requiring vasopressors. Bronchoscopy was performed that showed diffuse endobronchial and alveolar hemorrhage. Based on his social history, empiric treatment with doxycycline was begun and serology for leptospirosis was ordered which resulted in positive. After 9-days of mechanical ventilation and renal replacement therapy, he recovered and was discharged home. DISCUSSION: Leptospirosis disease is caused by Leptospira interrogans which is transmitted from the urine of wild animals and it can cause multi-organ involvement by initiating a cytokine storm.(1) Severe pulmonary hemorrhage syndrome (SPHS) can present as cough, massive hemoptysis, and is associated with circulatory collapse.(2) Chest radiography can show a wide variety of nodular infiltrates, ground glass opacifications, or multifocal consolidations which make the diagnosis difficult.(3) In non-endemic areas, clinical suspicion and social history play a pivotal role in the diagnosis. Suspected cases should be confirmed with serology (microscopic agglutination test). Mild disease is treated with tetracycline, while IV penicillin or ceftriaxone are preferred for severe disease, however beneficial effects are limited once organ dysfunction is progressed.(1) CONCLUSIONS: Due to the severity of Leptospirosis, the diagnosis should be made based on social history and a disproportionate rise of bilirubin. The mortality rate is significantly high in cases of pulmonary hemorrhage. Early treatment with antimicrobials is needed while serology testing is being performed. REFERENCE #1: Haake DA, Levett PN. Leptospirosis in humans. Curr Top Microbiol Immunol. 2015;387:65-97. doi:10.1007/978-3-662-45059-8_5 REFERENCE #2: Gouveia EL, Metcalfe J, De Carvalho ALF, et al. Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador, Brazil. Emerg Infect Dis. 2008;14(3):505-508. doi:10.3201/eid1403.071064 REFERENCE #3: Marchiori E, Lourenço S, Setúbal S, Zanetti G, Gasparetto TD, Hochhegger B. Clinical and imaging manifestations of hemorrhagic pulmonary leptospirosis: A state-of-the-art review. Lung. 2011;189(1):1-9. doi:10.1007/s00408-010-9273-0 DISCLOSURES: No relevant relationships by Ahad Azeem, source=Web Response No relevant relationships by Manasa Velagapudi, source=Web Response

A Study on Prevalence and Characterization of Candida Species in Immunocompromised Patients

Candida spp. is one among the major causes of nosocomial infection, with candidemia gaining increasing prevalence worldwide in parallel with mortality rates ranging from 10-49%. Epidemiology and predisposing factors of candidemia have changed since the number of patients receiving transplants and immunosuppressive therapy, the use of broadspectrum antimicrobials, and the number of AIDS patients have increased. Candidemia is more common among patients with subcutaneous and cutaneous candida infections, through percutaneous inoculation. Major predisposing factors for invasive candidiasis includes neutropenia, haematological malignancies, bone marrow transplantation, total parenteral nutrition, chemotherapy, invasive procedures, and immune-suppressive agents. This study analyses the risk factors of immunocompromised patients with candidemia and antibiogram of Candida spp. isolated from ICU patients. To evaluate the prevalence, distribution and antibiogram of Candida spp., associated risk factors, and outcome in candidemia patients. Blood samples received from patients with clinically suspected fungal infections were subjected to gram staining, culture, sugar assimilation &amp; fermentation, Candida Chrome agar (CCA) &amp; Corn meal agar for identification and speciation. Antifungal susceptibility tests were performed by disk-diffusion tests. Among a total of 337 samples received, 22 (6.5%) samples were positive for candida infections, of which Candida tropicalis 9 (41%) was the predominant isolate followed by C. albicans 5 (23%), Candida glabrata 4 (18%), Candida parapsilosis 2 (9%) and Candida krusei 2 (9%). Male patients had a higher prevalence of candidemia 15 (68.2%). Among the age group of 51-70 years, uncontrolled DM(Diabetes mellitus) and CKD (chronic kidney disease) were found to be the predominant co-morbidities with candidemia.

RelA Inactivation Converts Sulfonamides Into Bactericidal Compounds.

Folates are required for the de novo biosynthesis of purines, thymine, methionine, glycine, and pantothenic acid, key metabolites that bacterial cells cannot survive without. Sulfonamides, which inhibit bacterial folate biosynthesis and are generally considered as bacteriostats, have been extensively used as broad-spectrum antimicrobials for decades. Here we show that, deleting relA in Escherichia coli and other bacterial species converted sulfamethoxazole from a bacteriostat into a bactericide. Not as previously assumed, the bactericidal effect of SMX was not caused by thymine deficiency. When E. coli ∆relA was treated with SMX, reactive oxygen species and ferrous ion accumulated inside the bacterial cells, which caused extensive DNA double-strand breaks without the involvement of incomplete base excision repair. In addition, sulfamethoxazole showed bactericidal effect against E. coli O157 ∆relA in mice, suggesting the possibility of designing new potentiators for sulfonamides targeting RelA. Thus, our study uncovered the previously unknown bactericidal effects of sulfonamides, which advances our understanding of their mechanisms of action, and will facilitate the designing of new potentiators for them.

Pharmacogenetics and Pharmacokinetic of Azithromycin Eyedrops in Meibomian Gland Dysfunction Treatment

Meibomian gland dysfunction (MGD) is the leading cause of ocular surface disease throughout the world, which has a prevalence that varied widely from 3.5 to 70% according to age, sex, and ethnicity. Azithromycin (AZM) is the first azalidic antibiotic, a class of macrolide antibiotics, which has derived from erythromycin. It is widely used in clinical practice, not only for respiratory diseases and sexually transmitted infections but also for ocular diseases. azithromycin suppressed zymosan-induced mRNA expression and protein production of proinflammatory cytokines (tumor necrosis factor α and IL-1β), chemokines (IL-6 and RANTES), and MMPs (MMP-1, MMP-3, and MMP-9) by human corneal epithelial cells and suggested the potential for using azithromycin to treat ocular surface It controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes. The anti-inflammatory role of TGF-β1 has been recognized in different cell types by inhibiting proinflammatory cytokines including tumor necrosis factor α, IL-1, and interferon γ.The combination of a topical AZM solution 1.0% with corticosteroid (DEX 0.1%) was found superior in the comprehensive treatment of MGD after 2 weeks. AZM is a one of the safest antibiotics, well tolerated, and has special pharmacokinetic properties. Moreover, it has a broad antimicrobial spectrum. AZM is efficacious for the treatment of a lot of ocular diseases and may be included as monotherapy or in combination therapy in new treatment protocols for more ocular infections.

Antibiotic resistance in aerobic bacterial isolates from infected diabetic foot ulcers in North Eastern Tanzania: an urgent call to establish a hospital antimicrobial stewardship committee

Background: Diabetic foot ulcers (DFU) is among major health problems which impact the socio economic burden globally. We aimed at assessing the susceptibility pattern of antimicrobials in DFU infections among patients admitted in the surgical department at Kilimanjaro Christian Medical Centre (KCMC).Methods: This descriptive cross-sectional study was conducted from September 2018 through March 2019. Pus swabs were collected on the first day of admission by deep wound swabbing after irrigation with normal saline solution. Kirby-Bauer method was done according to the Clinical and Laboratory Standard Institute (CLSI) guidelines.Results: Sixty diabetic ulcer patients had 62 bacterial isolates. Majority of the isolates were gram negative 49/62 (79.03%). The most common isolate was Escherichia coli 15/62 (24.19%) followed by Pseudomonas aeruginosa 14/62 (22.58%), Proteus mirabilis 8/62 (12.9%) and Staphylococcus aureus 5/62 (8.06%). Klebsiella pneumoniae, coagulase negative Staphylococcus, Proteus vulgaris, and Streptococcus pyogenes each contributed 4/62 (6.25%) isolates. Of the 49/62 (79.3%) gram negative isolates, 8/49 (16.33%) were mono resistant, 30/49 (61.22%) were multiresistant, and 11/49 (22.45%) were susceptible. Of the multi-resistant isolates, E. coli 12/15 (80.00%), and P. aeruginosa 7/14 (50.00%) were predominant. A total of 39/62 (62.90%) isolates in patients contributed to poorer outcomes including loss of body part. Patients with ulcers infected by P. aeruginosa 11/39 (28.21%) had the highest number of surgical removal of body parts followed by E. coli 8/39 (20.51%). Gram negative bacteria were highly susceptible to amikacin 91.18%, meropenem 93.33% and imipenem 95.24%. Isolates susceptibility to ceftriaxone was 32%.Conclusions: Amikacin, meropenem and imipenem can be safely used as broad-spectrum antimicrobials in DFU. The standard of care remains culture and sensitivity of isolated microorganisms in combating diabetic foot ulcers infections.

Потенційне значення бактеріоцинів при етіологічному лікуванні інфекційних захворювань респіраторного тракту

Бактеріоцини являють собою рибосомно синтезовані гідрофобні антимікробні пептиди, що мають широкий антимікробний спектр дії, основним джерелом яких є грампозитивні бактерії. Бактеріоцини різних класів, діючи на грампозитивні і грамнегативні бактерії, використовують різні молекулярні механізми, функціонування яких призводить до порушення цілісності клітинної стінки або пригнічення синтезу нуклеїнових кислот чи протеїнів таргетних бактерій. На сьогодні описано понад 100 лантибіотичних пептидів, багато з яких використовують для розробки майбутніх лікарських засобів. Кілька лантибіотиків в даний час проходять клінічні та доклінічні випробування, у тому числі біоінженерні лантибіотики, які можуть зіграти ключову роль в подоланні антибіотикорезистентності до бактеріальних патогенів.