Evaluation of Microbiological Culture and Antibiogram of the Patient with Corneal Ulcer due to Exposure Keratitis in the Intensive Care Unit in Sina Farshchian Hospital (2019-2020)

Background: Since patients admitted to the intensive care unit have a compromised im-mune system and are more prone to infection than other patients, timely diagnosis and treatment of corneal ulcers among this group of patients can prevent vision loss. Therefore, it is necessary to treat eye infections and corneal ulcers promptly and economize prohibitive costs. Objective(s): Appropriate treatment with the most effective antibiotic before the answer is available to prevent corneal ulcer complications and blindness. Method(s): This study was conducted from November 2019 to November 2020 and after approval by the ethics committee of Hamedan University of Medical Sciences with the code of ethics: IR.UMSHA.REC.1398.716. First, the corneal secretions of 121 patients admitted to the intensive care unit of Sina Hospital are prepared by an ophthalmologist (after anesthetizing the cornea with tetra-caine drops and sterile swabs) and culture in four growth mediums (blood agar, chocolate agar, thio-glycolate, and EMB). Microbial cultures are examined after 48 hours and a fungal culture is examined one week later. Disc diffusions are placed in positive microbial cultures. Antibiotic susceptibility or resistance of the antibiogram was recorded. Other demographic data, including patients' age and sex, are extracted from ICU files. Also, test results and patient identifications are recorded in a checklist designed for this purpose. Result(s): Of all the antibiotics used against common bacteria, vancomycin (84%), colistin (80.43%), cefazolin (80%), and levofloxacin (60%) had the highest sensitivity and gentamicin (93.75%), ceftazidime (86.42%) Erythromycin (85%) had the highest resistance against isolated bacteria. Conclusion(s): The data obtained from this study showed that the most common microorganisms in the age group under the age of 30 years were Acinetobacter Baumannii, in the group of 30-60 years old was Klebsiella pneumonia, and age group over 61 years old was Staphylococcus aureus, and the most sensitive antibiotics in the age group under 30 years were vancomycin and levofloxacin and the age group30-60 were colistin and vancomycin and in the age group over 61 years were vancomycin and cefazolin.Copyright © 2023 Bentham Science Publishers.

Case Series of Burkholderia Pseudomallei Causing Melioidosis (Pulmonary, Cerebral, and Splenic Abscess)

Burkholderia pseudomallei is soil saprophytic Gram-negative bacilli that cause a fatal disease called melioidosis. Melioidosis is capable of causing cutaneous infection and systemic infections in the respiratory tract, cardiovascular, gastrointestinal, urinary, skin and soft tissue, and musculoskeletal and central nervous systems. Here, we report rare forms of pulmonary, cerebral, and splenic abscess case series of melioidosis caused by B. pseudomallei. Imported cases have been reported among tourists, immigrants, and soldiers who returned from endemic areas. The acquisition of infection is through percutaneous, inhalation, and ingestion of contaminated water;person-to-person transmission is very rare. Melioidosis cases are primarily found in the rainfall season and are usually associated with risk factors such as diabetes, alcoholism, and chronic renal diseases. However, 20-26% of cases were not associated with predisposing conditions. The identification is based on colony morphology, Gram stain, antibiotic susceptibility testing, and other supportive automated and molecular assays when we suspect B. pseudomallei. There are two phases, the intensive and eradication phases, in managing melioidosis. In the intensive phase, ceftazidime for 2 weeks showed efficacy in almost 50% of cases, and the eradication phase treatment with co-trimoxazole and doxycycline or amoxicillin/clavulanic acid for 3-6 months showed an excellent response. The improper clinical diagnosis and management of B. pseudomallei can lead to complications. Hence, early diagnosis with microbiological approaches such as culture, biochemical reactions, or automated systems available and antimicrobial sensitivity testing will cure the patient quickly without mortality.Copyright © 2023 The Authors.

Is there an increased incidence of bacteraemia among COVID-19 patients requiring critical care admission who have received IL-6 inhibitors?

Is there an increased incidence of bacteraemia among COVID-19 patients requiring critical care admission who have received IL-6 inhibitors? Introduction: Interleukin-6 (IL-6) inhibitors have been shown to reduce mortality in hospitalised COVID-19 patients. There is, however, concern that induced immunosuppression may increase the risk of secondary nosocomial infection. Objective(s): Our primary aim was to determine if there was increased incidence of bacteraemia in COVID-19 patients requiring critical care admission who had received IL-6 inhibitors compared to those who had not. Method(s): A retrospective review of all COVID-19 admissions to two critical care units in Liverpool from 4th March 2020 to 31st October 2021. Patients were divided into those who received an IL-6 inhibitor (sarilumab or tociluzimab) and those who did not. Hospital antimicrobial policy was to administer a five day prophylactic course of co-amoxiclav and clarithromycin for patients with severe COVID-19 during the study period. Blood culture results from 14 days before admission to critical care and 90 days after admission were included. The blood culture results comprised cultures taken in both critical care and on the wards. Data were linked and analysed using Stata V15.1 (StataCorp, Stata Statistical Software: Release 15, College Station, Texas, USA). Result(s): 894 patients were included in the study. 134 patients had at least one positive blood culture result. The most commonly identified pathogens were Coliforms (23/134, 17.2%), Enterobacter (22/134, 16.4%) and Escherichia coli (16/134, 11.9%). Of patients administered an IL-6 antagonist, 16.8% (114/565) developed a positive blood culture compared to 11.6% (20/172) who did not, p=0.096. We did not observe an increased frequency of antimicrobial resistant culture in the IL-6 administered group 22.8% (26/114) vs. 20.0% (4/20) in this cohort, p=0.781. Data have not been adjusted for demographic and clinical factors in this preliminary analysis. Conclusion(s): We observed a trend toward increased frequency of blood culture positivity in patients administered an IL-6 antagonist within this COVID-19 positive cohort but this was not statistically significant. Further analysis is required to adjust for relevant demographic and clinical factors.

Correlation Between the Suitability of Empirical and Definitive Therapies According to Culture Results with the Clinical Outcomes of Patients with Bacteremia Due to Carbapenem- Resistant Acinetobacter baumannii (CRAB) at Dr. Soetomo Tertiary Referral Hospital

Carbapenem administration is an important therapy for nosocomial infections due to MDRO, especially Acinetobacter baumannii. The global increase in carbapenem-resistant A. baumannii (CRAB) that causes this pathogen has significantly threatened public health due to the lack of adequate treatment options due to the very few currently available antimicrobial agents that actively fight CRAB. Antimicrobial resistance is a major negative impact of inappropriate antimicrobial prescribing. Ineffective empiric treatment (initial antibiotic regimen not sensitive to identified pathogens based on in vitro sensitivity test results) is associated with a higher rate of deaths compared to effective empiric treatment. In this study, we analyzed the correlation between the suitability of empiric and definitive antibiotics and the clinical outcomes of patients with bacteremia due to CRAB treated in the inpatient ward of Dr. Soetomo Tertiary Referral Hospital, Surabaya. There were 227 isolates of bacteremia due to CRAB, consisting of 156 carbapenem-resistant A. baumanni and 71 carbapenem-sensitive A. baumannii. There were 88 isolates that met the inclusion and exclusion criteria, and all of them were resistant to ceftriaxone, cefepime, and ciprofloxacin. A total of 29.5% of the isolates were sensitive to cotrimoxazole, 3.4% of the isolates were sensitive to tigecycline, and 2.3% of the isolates were sensitive to amikacin, levofloxacin, and cefoperazone sulbactam. Adequate empirical antibiotics and definitive antibiotics (sensitive based on culture sensitivity test) amounted to 12.5% and 27.3%, respectively. There is no significant correlation between the suitability of empiric and definitive therapies with the patients' clinical outcomes (death and length of stay).Copyright © 2022 Phcogj.Com.

Potential role of Pancreatic Stone Protein (PSP) as early marker of bacterial infection in COVID-19 patients

Background: Sepsis is a life-threatening condition that needs immediate diagnosis and treatment to maximize the chances of survival. Bacterial superinfection is a severe and frequent complication among COVID-19 patients and its diagnosis is challenging. Previous reports suggested that Pancreatic Stone Protein (PSP) may be a predictive biomarker for sepsis in critically ill patients. We report a case series of three COVID- 19 patients admitted to our intensive care unit (ICU) with risk of sepsis. Method(s): We daily monitored PSP, procalcitonin (PCT), and C-reactive protein (CRP) levels in three COVID- 19 patients admitted to our ICU. Microbiological sampling and antibiotic treatment were performed according to the ward organization and in case of clinical suspects for infection. Positive cultures and antibiotic treatment were retrieved from clinical charts and patients were followed from ICU admission up to a maximum of 20 days. Result(s): Patient 1 (male, 55 years-old, overweight, no other comorbidity) was admitted to the ICU in treatment with Ceftriaxone then interrupted on day 7. On day 2 he was intubated and piperacillin/tazobactam was started on day 12 for suspected hospital acquired pneumonia. PSP levels markedly increased on day 10 with no significant changes in CRP and PCT levels. On day 13 a positive bronchospirate for Klebsiella pneumoniae was found. Similarly, patient 2 (male, 70 years-old, mild emphysema and diabetes) was admitted to ICU without antibiotic and with a PSP level of 287 ng/ml. His conditions rapidly worsened in severe septic shock requiring intubation. CRP markedly raised 48-72 hours after PSP with only mild increase of PCT. Patient 3 (male, 78 years-old, no comorbidities) was admitted to ICU with high levels of PSP and piperacillin/tazobactam therapy was started. After 48-72 hours CRP levels increased with no significant changes of PCT. A positive bronchospirate for Ps. aeruginosa was collected on day 3. Conclusion(s): Our findings suggest a potential role of PSP as early biomarker of sepsis in critically ill COVID-19 patients. Daily PSP monitoring may anticipate an appropriate treatment of COVID-19 patients with a septic complication in comparison with the actual laboratory markers. Further studies are needed to confirm our hypothesis.

Impact of improving infection control and antibiotic stewardship practices on nosocomial infections and antimicrobial resistance in an oncology centre from India

Background: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Material(s) and Method(s): This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. Result(s): Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n = 6951;30.1%) followed by Klebsiella pneumoniae (n = 5801;25.1%) and Pseudomonas aeroginosa (n = 3041;13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. Conclusion(s): This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.Copyright © 2023 Indian Association of Medical Microbiologists

Risk of Microbial Transmission in Reusing Gloves after Alcohol-Based Hand Hygiene

Intro: The need for re-use of gloves as an alternative to single use was raised in times of resource shortages because during the coronavirus disease 2019 pandemic, marked increase in healthcare associated infection was reported, which might owing to shortage of personal protective equipment. we aimed to evaluate the risk of microbial transmission by comparing residual microorganism after multiple patient contact according to with or without gloves in clinical practice. Method(s): Three researchers made rounds of patients while touching the same area successively followed by alcohol-based hand rub: one with bare hands, one with single gloves, and one with double gloves. Hand imprints were obtained before and after rounds, and cultured to count colony-forming units (CFU). The number of colonies was compared between groups in a semi-quantitative manner by hand area. Finding(s): Mean CFU counts after round were 10.06 for bare hands, 31.22 for single-gloved hands, and 49.67 for double-gloved hands (p=0.084). The most commonly identified microorganism after rounding was coagulase-negative Staphylococci (77.8%, 42/54), followed by Bacillus species (62.9%, 34/54). Carbapenem-resistant Acinetobacter baumannii was confirmed from a pair of double-gloved hand specimens after the rounds. That round included a patient with the same organism with the same antibiotic susceptibility results. More microorganisms were remained after alcohol-based hand rub on gloved hands than on bare hands. Conclusion(s): From our results, the possibility of microbial transmission seems more likely in gloved hands than in bare hands even after alcohol-based hand rub. Therefore, we do not recommend the re-use of gloves after alcohol-based hand hygiene.Copyright © 2023

Recurrent Liver Abscess in a Non-Toxic Patient

Introduction: Liver abscesses are caused by direct spread from peritonitis, biliary tract infection or via hematogenous seeding from a distant source. Most are polymicrobial, however Escherichia coli and Klebsiella pneumoniae are the most common offending pathogens. Patients usually present with pain, fever, and clinical signs of infection. We describe a case of spontaneous liver abscess in a non-toxic patient that recurred 10 years after a previous abscess. Case Description/Methods: A 73-year-old-man with a history of type 2 diabetes mellitus, hypertension, CAD status post CABG and PCI 3 years ago, and abdominal aortic aneurysm status post endovascular aneurysm repair presented with 2 weeks of dark urine. After receiving his COVID-19 booster and influenza vaccinations, he developed flu-like symptoms with a self-resolving fever of 101.8degreeF. He had dark amber urine without dysuria or hematuria. Later, he experienced generalized weakness and decreased oral intake. Outpatient labs showed elevated liver function tests, and he was told to present to the ED. On arrival, he was afebrile with stable vitals. Physical exam was unremarkable. Laboratory evaluation showed a hemoglobin of 11.7 g/dL, sodium of 133 mEq/L, creatinine of 1.4 mg/dL, aspartate aminotransferase of 117 U/L, alanine aminotransferase of 212 U/L, alkaline phosphatase of 825 U/L, total bilirubin of 4.1 mg/dL, and direct bilirubin of 2.1 mg/dL. Triple-phase CT showed a 2.8 cm mass in the right liver lobe with linear enhancement. Ultrasound showed mixed echogenicity measuring 3.6 x 2.9 x 3.3 cm in segment 8 of the liver. On further evaluation, patient had an E. coli abscess diagnosed 10 years prior, managed with antibiotics and drainage. At that time, the abscess was within the right inferior liver lobe, similar to his current abscess. LFTs downtrended. Abscess was aspirated, with culture growing oxidase negative, gramnegative rods, likely E. coli. Patient started on ceftriaxone and metronidazole, to undergo colonoscopy as an outpatient and rule out colonic bacterial translocation. Discussion(s): Pyogenic liver abscess can result in significant morbidity and mortality because of worsening infection and sepsis. Abscesses occur because of spread from adjacent infection or after recent surgeries. Recurrence is very rare. Here, we describe a very unusual case of a pyogenic liver abscess growing E. coli in a non-toxic patient, with the same location and causative organism as an abscess managed 10 years prior. (Figure Presented).

A Thorn in his Side

History: A 20 year old D1 men's basketball player with a history of COVID the month prior presented with worsening low back pain. He denied any injury, but reported the pain started as low back discomfort after a basketball game the week prior. He noted a progression and radiation of pain down his right lower extremity to his toes. He had tried physical therapy and dry needling, as well as cyclobenzaprine and naproxen from team physicians with mild improvement. The pain worsened and he went to the ED for evaluation. He was afebrile and had a lumbar radiograph with no acute fracture, grade 1 anterolisthesis of L5 on S1. He was discharged home with norco. Over the next 2 days, he developed chills and in the context of his worsening back pain, his team physicians ordered an MRI. Physical Exam: BMI 26.9 Temp 97.9degree Heart rate: 73 Respiratory rate 14 BP: 124/64 MSK: Spine- Intact skin with generalized pain over lumbar area, worse over the right paraspinal musculature. 5/5 strength of bilateral lower extremity flexion and extension of his hips, knees, and plantar and dorsiflexion of ankles and toes. Bilateral intact sensibility in the sciatic, femoral, superficial, and deep peroneal, sural, and saphenous nerve distributions. Slightly diminished sensibility over the right deep peroneal nerve distribution compared to left. 2/4 patellar and achilles DTRs. No clonus, downgoing Babinski sign. Positive straight leg raise at 45 degrees with the right lower extremity. Differential Diagnosis: 141. Sciatica 142. Lumbar Muscle Strain 143. Disk Herniation 144. Spondylolisthesis 145. Vertebral Osteomyelitis Test Results: CBC:WBC10, HGB13.2, neutrophils 75.7% (red 45%-74%). Unremarkable CMP. CRP =7.31, ESR 23 Blood culture negative, throat culture negative. TB test negative. COVID test negative. Flu test negative. Urine culture and UDS negative. HIV test negative. Procalcitonin of 0.07. IR guided aspiration and bacterial Culture yielded MSSA. MRI w/contrast: showing L1-L4 facet edema concerning for infectious spondylitis, intramuscular, and epidural abscess. Final Diagnosis: Acute intramuscular abscess, vertebral osteomyelitis, with epidural abscess. Discussion(s): Vertebral osteomyelitis is a serious but quite rare disease in the immunocompetent, elite athlete population. Staphylococcus Aureus is the culprit a majority of the time, with only 50% of cases showing neurologic symptoms. This case was unique given the proximity to a dry needling treatment which is the only explainable vector of infection, normal blood cultures in this disease which hematogenously spreads, negativeHIV and other infectious disease testing, and otherwise benign history. Early recognition of this disease yields better outcomes and reduces incidence of severe debility. 5% to 10%of patients experience recurrence of back pain or osteomyelitis later on in life. Outcome(s): Patient was hospitalized and started on Cefepime and Vancomycin. Had an echocardiogram revealing changes consistent with athlete's heart without signs of vegetation on his cardiac valves. Neurosurgery declined to treat surgically. He continued to improve until he was ultimately discharged on hospital day 4 with a picc line and Nafcillin and was later changed to oral augmentin per ID. Follow-Up: By his 6 week follow-up visit with infectious disease and the team physicians, his back pain had completely resolved and was cleared to start a return to play protocol. There was no progression of disease since starting antibiotics, and no recurrence of back pain since treatment.

Screening Strategies in Different Resource Settings

Health care-associated infections/ Hospital-acquired infections (HAIs) have a significant impact on patients' morbidity and mortality. The risk of HAIs in resource-limited settings (RLS) has been reported 2-20 times higher than that in developed countries. Moreover, multi-drug- resistant organisms (MDROs) have emerged and spread throughout the world. In addition, increases in HAIs were observed during the COVID-19 pandemic throughout the world.Thus, screening strategies/surveillance of MDROs were recommended as a core component of infection prevention and control (IPC) measures for the effective HAIs prevention. We review and summarize current critical knowledge on screening strategies in different resource settings, especially on guidelines for the prevention and control of carbapenem- resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPsA) in health care facilities. The guidelines (especially WHO) were strongly recommended for surveillance of CRE-CRAB-CRPsA infections and surveillance cultures of asymptomatic CRE colonization. There were conditional recommended on surveillance cultures of the environment for CRE-CRAB-CRPsA colonization/contamination. The surveillance cultures (stool samples or rectal swabs) allowed the early introduction of IPC measures to prevent transmission to other patients and the hospital environment. Given the clinical importance of CRE-CRAB-CRPsA infections, regular ongoing active surveillance of infections were required in all microbiology laboratory settings. In addition, surveillance cultures for asymptomatic CRE colonization should also be performed, guided by local epidemiology and risk assessment. The surveillance cultures of asymptomatic CRE colonization should be considered for patients with previous CRE colonization and patients with a history of recent hospitalization in endemic CRE settings or contacted CRE colonized/ infected patients. In contrast, the evidence available on surveillance cultures for CRAB and CRPsA colonization in asymptomatic patients was not sufficiently relevant for the recommendation. Nowadays, the CRE surveillance strategies have been implemented in various methods from traditional culture- based methods to molecular assays. The limitation of microbiology laboratory capacity for MDROs in RLS was concerning. However, the surveillance data would help with appropriate IPC measure implementation and outbreak investigations. Thus, the proper screening strategies and strengthening microbiology laboratory capacity, especially in RLS are challenge for improving IPC measures and patient outcomes.Copyright © 2023

Characterization of secondary bacterial and fungal infections in ICU hospitalized patients with COVID-19: retrospective observational study

Introduction: We aimed to describe the incidence, risk factors, and clinical outcomes of bacterial and fungal co-infections and superinfections in intensive care patients with COVID-19 in a retrospective observational study. Method(s): A retrospective cohort of intensive care patients with confirmed SARS-CoV-2 by PCR was analysed from January to March 2021. This was contrasted to a control group of influenza-positive patients admitted during 2012-2022. Patient demographics, microbiology and clinical outcomes were analysed. Result(s): A total of 70 patients with confirmed SARS-CoV-2 were included;6 (8.6%) of 70 had early bacterial isolates identified rising to 42 (60%) of 70 throughout admission. Blood cultures, respiratory samples, and urinary samples were obtained from 66 (94.3%), 18 (25.7%) and 61 (87.1%) COVID-19 patients. Positive blood culture was identified in 13 patients (18.6%). Bacteraemia resulting from respiratory infection was confirmed in 3 cases (all ventilator-associated). Line-related bacteraemia was identified in 9 patients (6 Acinetobacter baumannii, 4 Enterococcus spp. and 1 Pseudomonas aeruginosa and 1 Micrococcus lylae). No concomitant pneumococcal, Legionella or influenza co-infection was detected. Invasive fungal infections with Aspergillus spp. were identified in 2 cases. Pneumococcal coinfections (7/68;10.3%) were identified in the control group of confirmed influenza infection;clinically relevant bacteraemias (6/68;8.8%), positive respiratory cultures (15/68;22.1%). The rate of hospital- acquired infections was 51.4% for COVID-19 and 27.9% for influenza. Longer intensive care stay, type 2 diabetes, obesity and hematologic diseases were independent risk factors for superinfections in the COVID-19 cohort. Conclusion(s): Respiratory coinfections occurred in influenza but not in COVID-19 patients. The rate of hospital-acquired infections (51.4% for COVID-19;27.9% for influenza) was unexpectedly high in both groups.

Centella asiatica extract inhibits Mycobacterium tuberculosis growth in rat tuberculosis models

Background and Aims: The covid-19 pandemic has reversed years of progress in the fight to end tuberculosis. So, the discovery of new drugs as antituberculosis is very much needed. Our previous studies have shown that the extract of Centella asiatica is able to inhibit the growth of Mycobacterium tuberculosis in vitro and requires further research. The aims of this study is to prove the effect of Centella asiatica inhibit Mycobacterium tuberculosis in rat model tuberculosis. Method(s): The protocol in this study was approved by the veterinary ethics committee of Airlangga University. The rat tuberculosis model was induced by intrathecal injection of a suspension of Mycobacterium tuberculosis strain H37 Rv. Twenty-eight tuberculosis rat were randomly divided into four groups. Groups 1,2, and 3 were treated with ethanol extract of Centella asiatica at 375 mg/kgBW, 750 mg/kgBW and 1500 mg/kgBW, and the fourth group was the control group. Centella asiatica extract is administered orally via an intragastric feeding tube for two weeks, once daily At the end of the experimental period, rats were sacrificed by cervical decapitation. The left lung tissue was taken aseptically and cultured on Middlebrook 7H10. Result(s): The results showed that there was no bacterial growth on the culture media in the group that received Centella asiatica extract at a dose of 750 and 1500 mg/kg BW. Conclusion(s): The conclusion in this study, that Centella asiatica extract inhibit the growth of Mycobacterium tuberculosis at doses of 750 and 1500 mg/kg BW. We thank the Directorate of Research and Community Services, the Directorate General of Higher Education, and Ministry of Education and Culture in Indonesia for the financial supportCopyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Efficacy of home respiratory culture kits in people with cystic fibrosis

Background: Respiratory cultures are an important part of clinical care for people with cystic fibrosis (CF). Telemedicine visits during the COVID-19 pandemic have not allowed for routine collection. To address this, the University of Michigan Adult Cystic Fibrosis Program mailed home culture kits to patients. We hypothesized that results from home sputum samples would be consistent with prior cultures obtained in sputum collected in clinic but that self-collected throat swabs would provide false-negative results. We also sought to determine percentage return rate. Method(s): Adults with CF were sent culture kits containing a specimen cup and a throat swab. Patients had the choice to submit either sample for processing. Medical personnel provided written instructions with the culture kits and, on occasion, instructed patients on proper collection techniques via phone. Samples were then refrigerated for up to 24 hours before a delivery service returned the specimen to a University of Michigan laboratory for analysis. Data collected from December 2020 to December 2021 (N = 77) included percentage return rate, result, source, and presence of microorganisms. Pairwise culture data of samples collected in clinic versus home-collected samples within 1 yearwere included in the analysis. Descriptive statistics and Cohen kappa correlation coefficients were computed for all culture data and subgroups (Table 1A-E). Result(s): Of 77 culture kits returned, 46 had corresponding clinic samples collected using the same method, and the remaining 21 were collected using different methods (throat swab vs sputum sample). Overall, approximately 200 kits were mailed to patients, with a return rate of 38.5%. A similar percentage of positive culture results was obtained with same method of collection: sputum and throat samples (Table 1C, D, E), although the discordance rate between cultures collected in clinic and at home ranged from approximately 10% to 30%. Correlation between clinic and home culture data was generally good throughout, except for clinic Table 1 ( 115): Analysis of respiratory culture results for (A) all cultures, (B) different collection, and (C, D, E) same collection method. *p < 0.05. Cohen kappa correlation coefficient between groups: poor agreement <0.20;fair agreement = 0.21-0.40;moderate agreement = 0.41-0.60;good agreement = 0.61-0.80;very good agreement = 0.81-1.00. PsA = Pseudomonas aeruginosa;Staph = Staphylococcus aureus.(Table Presented)versus home throat swabs, probably because of a lowevent rate in the small sample size. Conclusion(s): The data suggest that, overall, clinic and home culture kits provide similar positive results, although discordance in specific culture results was common. This may be due to natural fluctuations from culture to culture in people with CF. A limitation of this study is that the cultures being compared in our study were not completed on the same day. Nevertheless, our data also indicate that collection technique may influence results for certain microorganisms. How these differences might influence antibiotic selection and treatment outcomes in the era of telemedicine requires more investigation. The return rate was found to be relatively low, demonstrating the need for interventions to improve patient outreach and compliance.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Outside The Box But All Squeezed In: A 23- year-old Man With Progressive Dyspnea After Overseas Travel

Case Presentation: A 23-year-old previously healthy man presented with progressive dyspnea. Physical examination revealed jugular venous distension and lower extremity edema. Laboratory testing demonstrated elevated B-type natriuretic peptide (193 pg/mL) and normal high sensitivity troponin. Echocardiogram revealed small pericardial effusion, respiratory variation in diastolic flow across the mitral valve, diastolic septal bounce, and annulus reversus (Figure). The differential diagnosis for constrictive pericarditis was broadly considered in the context of a recent febrile illness and frequent travel to Hawaii and Vietnam;we included infectious, autoimmune, and malignant etiologies. Cardiac magnetic resonance imaging revealed thickening and diffuse enhancement in the pericardium as well as ventricular interdependence. Chest CT identified hilar and anterior mediastinal lymphadenopathy. Laboratory testing was positive for QuantiFERON gold and negative for COVID-19, HIV, and ANA. Transbronchial biopsy demonstrated non-necrotizing granulomas with negative acid-fast bacilli smear, culture, and polymerase chain reaction for mycobacterial DNA. Reexamination identified a red-brown plaque on the patient's thigh;biopsy showed granulomatous inflammation and rod-shaped organism with positive FITE staining. A presumed unifying diagnosis was made of extrapulmonary tuberculosis (TB) complicated by constrictive pericarditis. Discussion(s): Despite being a primarily pulmonary disease, systemic involvement can occur with TB with the heart being one of the most common extrapulmonary sites. This case highlights 1) the utility of extra-cardiac diagnostic testing (e.g., dermatologic biopsy) in the diagnosis of constrictive pericarditis, and 2) the diagnostic challenge associated with extrapulmonary TB, particularly paucibacillary disease that requires a detailed social history with "out-of-the-box" thinking.

Bacterial and viral upper and lower airways infection in people with cystic fibrosis in stable condition

Background: Bacterial and viral airway infections are adverse factors for prognosis in people with cystic fibrosis (CF). The role of viral infections is unclear. Proper microbiological follow-up is essential, and the correlation between upper (UAW) and lower airway (LAW) microbiology may be important for lung disease management. We aim to evaluate airway microbiology in patients in stable clinical condition. Method(s): Between September 2021 and March 2022 in the Florence CF center, 144 nasal lavage-throat swab paired samples were collected from 72 clinically stable people with CF not chronically colonized by Pseudomonas aeruginosa. The study enrolled 59 children (median age 9, range 2-16) and 13 adults (median age 28, range 18-59). LAW specimens (72)were sampled as throat swab and UAWspecimens (72)were randomly collected by nasal lavage with two methods-Mainz (44) or Ryno-set (28). We performed conventional microbiological analyses on all samples. To screen for respiratory viruses, multiplex polymerase chain reaction (BioFire FilmArray RP 2.1 Plus) was performed. Respiratory symptoms and forced expiratory volume in 1 second (FEV1) valueswere evaluated for all patients. Result(s): Twenty-one (29%) patients tested positive for at least one virus in UAW and LAW specimens. The most frequently identified viruses were human rhinovirus or enterovirus (22%) and respiratory syncytial virus (6%). Two (3%) patients tested positive for SARS-CoV-2. Concordance between sampling methods for viral detection in UAW and LAW specimens was observed in 59 paired samples (82%), including 40 patients with no viral infections and 19 virus positive for both samples. Discordance was described in 13 subjects;10 of 13 did not show viral infection in nasal lavage. Twenty-one percent of positive nasal lavage was performed using Ryno-set and 36% using the Mainz approach. The prevalent bacteriumwas Staphylococcu aureus in UAW (53%) and LAW (69%) cultures, followed by Enterobacteriaceae (UAW 8%, LAW 6%), methicillin-resistant S. aureus (UAW 7%, LAW 6%), P. aeruginosa (UAW 4%, LAW 6%), and other clinically relevant gram-negative bacteria such as Achromobacter xylosoxidans, Stenotrophomonas maltophilia, and Ochrobactrum anthropi (UAW 7%, LAW 13%). Nasal lavage performed with Ryno-set tested positive in 72% of patients, and 64% of Mainz lavage were positive. Mainz nasal lavage showed different S. aureus and P. aeruginosa isolations (48% and 5%, respectively) than the samples collected with Ryno-set technique (61% and 4%, respectively). Concordance between sampling methods for bacterial detection in UAW and LAW was the same with the two methods (53%). Bacterial and viral infections were found in UAWand LAWof stable people with CF, but no clinical correlation was observed. Conclusion(s): The two methods of UAW lavage had slight differences in performance. Virus infection appeared to be less prevalent than bacterial infection in UAWand LAW.We did not find correlations between presence of viruses and respiratory symptoms, but further investigation is needed for a better understanding of the clinical role of viral infection in people with CF.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Value of Biofire Filmarray pneumonia panel in evaluating secondary infection in critically ill patients with Coronavirus disease 2019.

Objective To explore the application value of Biofire Filmarry pneumonia panel (PN) in detection of secondary and concomitant pathogen among critically ill patients with coronavirus disease 2019(COVID-19). Methods We consecutively included and analyzed the clinical data of critically ill patients with COVID-19 transferred to the ICU from February to April 2020 in the Sino-French Campus of Wuhan Tongji Hospital. Samples of Bronchoalveolar lavage fluid obtained by bedside bronchoscopy were sent for Biofire Filmarray PN and standard culture concomitantly. We compared the results of two methods and evaluated their concordance. Results In total, 21 critically ill patients with COVID-19 were included and 54 samples were tested, including 33 (61.1%) Biofire Filmarray PN tests (21 patients) and 21 (38.9%) standard cultures (14 patients), in which 19 pairs (38 samples) underwent both tests simultaneously. In Biofire Filmarray PN group, the turnaround time was about 1 hour. There were 74 positive results in 32 samples (97.0%) from 20 patients, including 29 cases(39.2%) of Acinetobacter baumannii complex, 21 cases (28.4%) of Pseudomonas aeruginosa, 16 cases (21.6%)of Klebsiella pneumoniae, 5 cases (6.8%) of Escherichia coli, 1 case (1.4%)each of Enterobacter cloacae, Haemophilus influenzae, and respiratory syncytial virus. In the standard culture group, the turnaround time was about 3 days. 19 positive results returned in 16 (76.2%) samples from 11 patients, including 8 cases (42.1%) of Pseudomonas aeruginosa, 6 cases (31.6%) of Acinetobacter baumannii, 4 cases (21.1%) of Stenotrophomonas malt and 1 case (5.3%) of Myxobacterium. Among the 19 pairs of "back-to-back" specimens, 15 pairs were concordant, and the agreement ratio was 78.9%. Conclusions Acinetobacter baumannii and Pseudomonas aeruginosa may be the common pathogens of secondary or concomitant infection in critically ill patients with COVID-19. Biofire Filmarray PN is a rapid diagnostic test and has application value in such patients;its sensitivity and accuracy require further investigation with larger sample sizes.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Impact of elexacaftor/tezacaftor/ivacaftor on Pseudomonas aeruginosa acquisition and chronic infection at a single pediatric cystic fibrosis center

Background: As cystic fibrosis (CF) lung disease progresses, the airways become colonized with opportunistic pathogens such as Pseudomonas aeruginosa secondary to airway surface liquid depletion. Acquisition of P. aeruginosa is associated with decline in lung function and increase in treatment burden and mortality. In October 2019, the Food and Drug Administration approved elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), a highly effective modulator therapy (HEMT) for individuals aged 12 and older with one copy of the F508del CFTR mutation. ELX/TEZ/IVA increases the amount of and function of CF transmembrane conductance regulator (CFTR) in the respiratory epithelium, increasing mucociliary clearance (MCC) and reducing static airway mucous, a major trigger for chronic infection and inflammation. Method(s): A retrospective analysis of inhaled tobramycin (iTOB) prescriptions prescribed between January 1, 2016, and December 31, 2021, was performed. This captured data before and after ELX/TEZ/IVA approval at Children's Mercy Kansas City (CMKC). The number of individuals with new P. aeruginosa acquisition was determined by identifying electronic prescriptions for iTOB eradication courses. An eradication course was defined as a first lifetime prescription for iTOB or a new prescription for iTOB submitted at least 1 year after a previous prescription. The number of individuals considered chronically infected with P. aeruginosa was determined by identifying individuals receiving chronic iTOB prescriptions and confirmed by respiratory cultures indicating chronic infection based on the Leeds criteria (P. aeruginosa recovered in >=50% of airway cultures in the previous 12 months). Result(s): Eradication courseswere prescribed to 34 individuals in 2016 (15% of people receiving care at CMKC). The number of eradication prescriptions declined in 2020 and 2021, with only 15 (7%) individuals prescribed eradication therapy in 2020 and 12 (5%) in 2021. A similar pattern was observed for prescriptions for chronic infection. In 2016, 57 individuals (25% of our patient population) were receiving iTOB for chronic P. aeruginosa infection. Reductions were seen in 2020 and 2021, with 28 (13%) and 20 (9%) individuals prescribed chronic therapy, respectively. The number of individuals prescribed iTOB for P. aeruginosa eradication and chronic infection per year is represented in Figure 1.(Figure Presented)Conclusions: CMKC experienced a decrease in the number of courses of iTOB prescribed over the last 6 years. HEMT use is associated with greater MCC and anti-inflammatory effects affecting the airway microbiome. The decrease in respiratory cultures growing P. aeruginosa likely reflects these phenomena. A confounding factor is the SARS-CoV-2 pandemic and widespread use of HEMT. Clinic closures and implementation of telemedicine limited in-person patient visits during 2020 and 2021. Despite limited in-person visits, the average number of respiratory cultures per individual at CMKC in 2020 was 3.5, which is consistent with previous years.Wewere able to obtain frequent surveillance cultures through implementation of a drive-through respiratory specimen collection process. Hence, the decrease in number of iTOB courses cannot be attributed to a decrease in frequency of respiratory cultures, although we cannot assess the impact of school closures and a decrease in social gatherings on new P. aeruginosa acquisition or chronic infection. Looking at all these variables, the widespread use of HEMT likely played a significant role in reducing new P. aeruginosa acquisition and chronic P. aeruginosa infection.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Anaphylaxis to Cyclophosphamide Metabolites during Lymphodepletion for CAR-T Therapy

Background: Cyclophosphamide (Cy) is used in hematopoietic stem cell transplant (HSCT) preparative regimens and lymphodepletion for chimeric antigen receptor T-cell (CAR-T) therapy. We describe a case of cyclophosphamide hypersensitivity in a pediatric patient during CAR-T therapy. Case description: A 13 year old boy was diagnosed with very high risk ALL in 2015 and had 2 isolated CNS relapses treated with intensified chemotherapy (chemo) and cranial radiation (1st relapse) and Blinatumomab with intrathecal (IT) chemo followed by sibling donor HSCT (2nd relapse). At age 19, and 18 months after HSCT, he had a 3rd CNS relapse treated with IT chemo and referral for CAR-T therapy. At our center, leukapheresis and CAR-T production (Novartis) were performed. Later, during lymphodepletion with fludarabine (Flu) and Cy, physiologic replacement hydrocortisone (HC) was briefly held to prevent interference with CAR-T function. After 3 days of Flu/Cy, he developed fever and hypotension requiring inotropic support. Hypotension and fever resolved with stress dose HC and antibiotics and was attributed to culture-negative sepsis and adrenal crisis. CAR-T infusion was subsequently delayed by skin GVHD requiring glucocorticoids and COVID-19 infection treated with convalescent plasma and nirmatrelvir/ritonavir. Physiologic HC replacement was continued when he was re-admitted for CAR-T therapy, but he again developed fever, diffuse erythema and shock in hours following the first dose of Cy necessitating stress dose HC, antibiotics, inotropes, and mechanical ventilation. Negative blood cultures and ongoing physiologic HC replacement suggested an alternative explanation for shock. Case reports of anaphylaxis to Cy metabolites implicated Cy as the causative agent so it was discontinued. After recovery, CAR-T cells were infused without complications. In the following weeks, he had no evidence of recurrent leukemia but was persistently pancytopenic. A sibling donor stem cell boost was proposed but the patient accepted only palliative care. He had several opportunistic infections before succumbing to E. coli sepsis. Discussion(s): The first episode of shock was initially attributed to adrenal crisis and sepsis, although no organism was identified. The second episode appeared anaphylactic in timing and clinical presentation with adequate HC replacement and negative cultures, suggesting Type I hypersensitivity. The patient previously received Cy uneventfully before HSCT, suggesting that the donor-derived immune system was the source of new Cy hypersensitivity. Onset of anaphylaxis within hours rather than minutes after Cy administration supports hypersensitivity to Cy metabolites rather than to the drug itself. This case highlights the importance of consideration of sensitivity to Cy metabolites as well as acquired donor-specific allergy even when alternative explanations are likely.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Risk factors associated with meeting the standard of care and use of telehealth in 2020 among persons with cystic fibrosis in the United States

Background: The COVID-19 pandemic led to a dramatic decrease in clinic visits for essential health care needs for individuals with cystic fibrosis (CF), but the decline in in-person visits was accompanied by a rapid pivot by many CF care centers to provide telehealth services, similar to the U.S. health care system as a whole. In the absence of in-person visits, we hypothesized that individuals with CF who used telehealth services would be more likely to meet standard of care as defined by Cystic Fibrosis Foundation (CFF) guidelines than individuals who did not use or did not have access to telehealth. We also hypothesized that telehealth use or access would be lower in particular demographic groups based on disparities seen in non-CF telehealth studies. Method(s): We used 2019 and 2020 data from the U.S. CFF Patient Registry (CFFPR) to describe patterns of telehealth use and evaluate associations between patient-level characteristics and use of telehealth in 2020 to achieve standard of care. We quantified the extent to which persons with CF received the recommended components of the care model, comparing 2019 and 2020. A risk factor analysis was implemented to identify patient characteristics associated with attaining standard of care and use of any telehealth in 2020 using multivariable logistic regression. Result(s): A total of 28,132 CFFPR participants were included in the study. The proportion of individuals meeting the individual standards of CF care was lower in 2020 than 2019 for every indicator and lower in adults than in children. In 2020, telehealth use was high among CFFPR participants, with 71% of children and 73% of adults reporting one or more telehealth encounter. In adults, demographic, socioeconomic and CF-related disease covariateswere significantly associated with achieving the overall standard of care and use of telehealth. In the pediatric population, Black race, Hispanic ethnicity, and markers of lower socioeconomic status were associated with lower odds of telehealth use. In all analyses, having received the standard of care in 2019 was associated with higher odds of reported telehealth use (odds ratio (OR) 1.28, 95% CI, 1.16-1.41 in children) and achieving the recommended elements of the CF care model in 2020 (OR 2.36, 95% CI, 2.11-2.64 in children;OR 2.61, 95% CI, 2.19-3.12 in adults). Conclusion(s): Fewer individuals with CF met standards of care in the United States in 2020 than in 2019, probably because of pandemic-related effects, although use of telehealth services increased adherence to some standards of care, such as four or more encounters of any type, mental health screening, and annual ancillary consultations, but not four pulmonary function tests or bacterial cultures annually. The analysis suggests that there are disparities in access to telehealth services. Adults or children who were Black or Hispanic or whose self or parents had lower levels of education had lower odds of telehealth use. Overall, CF care centers in the United States have proven remarkably adept in pivoting care models during the pandemic, and some aspects of these models are important to be retained in a post-pandemic era.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Respiratory microbiological surveillance in people with cystic fibrosis-analysis of respiratory samples before and after elexacaftor/tezacaftor/ivacaftor in a large adult U.K. cystic fibrosis center

Background: Pathogen surveillance is crucial but has become more challenging in the era of highly effective modulator therapy (HEMT), with many people with cystic fibrosis (PwCF) noting a considerable reduction or even absence of sputum on elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). This challenge has been exacerbated by reduced face-toface contact with patients because of variable COVID-19 government restrictions on travel and social interaction (lockdowns) since March 20, relying on PwCF returning high-quality samples by mail. For those with pre-established bronchiectasis, it is likely that chronic infections and risk of new acquisition of infections remain on ELX/TEZ/IVA, although registry data suggest less prevalence of respiratory microorganisms on IVA [1]. We aimed to examine the impact of ELX/TEZ/IVA on frequency of respiratory pathogen surveillance and microorganism growth in our large, adult CF center. Method(s): A retrospective analysis of pathology results from respiratory samples received from March 19 to December 21, 2020, was completed for all patients commenced on ELX/TEZ/IVA at our CF center. Result(s): Respiratory samples from 216 PwCF who had commenced ELX/ TEZ/IVAwere analyzed. Median start date of ELX/TEZ/IVAwas October 10,2020. Before ELX/TEZ/IVA, the average number of respiratory samples per month was 108. This declined by 55% to an average of 48 per month when the first 50 PwCF commenced on ELX/TEZ/IVA and to 20 per month (82% reduction from pre-ELX/TEZ/IVA) when 100 PwCF had commenced ELX/ TEZ/IVA. The number of positive samples per month decreased from January 20, 2020, correlating with the introduction of ELX/TEZ/IVA and the reduction of respiratory samples received (Figure 1). The proportion of cough swabs and sputum samples remained similar from March 19 to December 21, 2020. (Six-month average showed that 19% of samples were cough swabs and 80% sputum for March to June 2019 and July to December 2021). We found no significant changes in proportion of samples positive for non-Pseudomonas spp. gram-negative organisms, Burkholderia spp., or gram-positive organisms (predominantly S. aureus) isolated over the period. There was a reduction by more than 50% of fungi and Candida spp. and a slight trend toward an increase in Pseudomonas spp. (mainly P. aeruginosa). Forty percent of PwCF who had one respiratory sample after ELX/TEZ/IVA initiation and 20% of those who had two or more samples showed a change in organism growth after ELX/TEZ/IVA initiation. In nearly 50% of these cases, the organism changed from gram negative to gram positive (P. aeruginosa to S. aureus in 69% of cases).(Figure Presented) Figure 1. Number of positive respiratory samples per month and number of people with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor March 19 to December 21, 2020 Conclusion(s): The introduction of ELX/TEZ/IVA and its impact on sputum production has reduced surveillance of our patients' respiratory microbiology. This has been exacerbated by reduced face-to-face contact with patients due to the COVID-19 pandemic. The trends showa reduction in the isolation of fungi and yeasts and a slight increase in isolating Pseudomonas spp. In those who we have seen a change in organism growth, many have gone from gram-negative to gram-positive organisms. These data highlight the challenges of monitoring for new positive cultures and changes in microbiology cultures in the era of HEMT.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved