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Introduction: Intensive care outcomes in patients with cirrhosis are relatively poor. The comparison between outcomes, especially related to infections, remains unclear in those with and without cirrhosis. With the emergence of resistant and fungal organisms, the changes in infection profiles over time are important to analyze. The aim of this study is to determine the impact of cirrhosis and infections on inpatient death over time in a qSOFA-matched cohort of patients with and without cirrhosis. Method(s): Inpatients admitted to ICUs throughout 2015-2021 were analyzed. Patients with cirrhosis were matched 1:1 by age, gender, and admission qSOFA to patients without;COVID-positive patients were excluded. Admission demographics, labs, the reasons for ICU transfer, infections, and inpatient death or hospice referral were obtained for each patient. Comparisons were made between patients with and without cirrhosis and those who died/referred to hospice versus not. Logistic regression for death/hospice was performed. In patients with cirrhosis, the culture results were compared over the years. Result(s): 1669 patients;833 cirrhosis and 836 non-cirrhosis patients were included. Patients with cirrhosis had higher rates of infection, positive culture, abdominal infection, and bacteremia. They also had higher gram-positive and fungal infections with a higher rate of VRE. They showed a greater organ failure load, death, and hospice referral compared to patients without cirrhosis. Logistic regression showed that cirrhosis (OR 4.0, p< 0.0001), admission qSOFA (1.60, p< 0.0001), WBC (1.02, p=0.003), reasons for ICU (altered mental status 1.69, hypotension 1.79, renal support 2.77, respiratory failure 1.79, CVA 1.96, all p< 0.0001) with Infection (1.77, p< 0.0001, >1 microbe isolated 1.86, p=0.05) were risk factors for death/hospice. The infection trend in the cirrhosis group showed a significant decrease in positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time. Conclusion(s): Despite matching for demographics and qSOFA, patients with cirrhosis had higher risks of death and organ failures. They were more likely to develop gram-positive and fungal infections with multiple organisms and VRE. Time trends in cirrhosis showed lower rates of positive cultures and gram-negative infections and an increase in fungal and gram-positive infections over time, which should encourage re-evaluation of diagnostic and prophylactic strategies in cirrhosis-related infections. (Figure Presented).
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Introduction: The prevalence of antimicrobial resistance genes ARGs and their resistance genetic mechanisms among Covid- 19 patients are yet to be identified. The human microbiome is a significant reservoir of antimicrobial resistance genes. The overprescription of antimicrobials can select multi-resistant bacteria and modify the repertoire of ARGs in the gut. The World Health Organization has reported 148 million hospitalized cases worldwide. Objective(s): The purpose of the current study is to explore the genetic mechanisms of antimicrobial resistance among hospitalized COVID-19 patients, furthermore, to review their antibiotic resistance gene occurrence. Methodology 438 Microbiome of clinical hospitalized COVID-19 positive cases with 11 129 isolates were downloaded from the EMBL's European Bioinformatics Institute and the NCBI Pathogen Detection using the following keywords AMR, mechanism of resistance, and COVID-19 SARS CoV 2 bacterial Infection.We also have used the Comprehensive Antibiotic Resistance Database Card, and RESfinder are used for the metagenomics analysis based on programming languages JavaScript and R (v. 4) for data analysis. Result(s): We explored the AMR diversity among prevalent microbes(n = 410), including Klebsiella pneumoniae, Acinetobacter baumannii E. coli, Salmonella, Enterobacter and Pseudomonas aeruginosa.We found that Enzyme activation (72.7%) was the most prevalent mechanism due to the fosA gene 54.5%. Then the aadA2 gene (18%) and catA1 gene(9%). Moreover, the Increased efflux mechanisms were detected in Escherichia coli towards Quinolone using the oqxA gene (17.3%). FosA was also intermittently found in Salmonella (9.8%), and Pseudomonas aeruginosa (7.8%). Conclusion(s): We anticipate that FosA homologous is prevalent in Gram-negative bacterial infections among hospitalized COVID-19 patients, and it encodes for Fosfomycin resistance. The findings might shed light on controlling Fosfomycin resistance among hospitalized patients with COVID-19.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Introduction: It is important to know the risk factors for death in reducing mortality in patients with Stenotrophomonas maltophilia infections. The purpose of this study was to examine the risk factors associated with mortality in hospitalized patients with S. maltophilia infections. Material(s) and Method(s): Patients with S. maltophilia infections aged 18 years and older who were hospitalized in Haseki Research and Training between January 1, 2017, and April 30, 2022, were included in the study. The patients were divided into two groups, non-survivors and survivors, and the clinical features and laboratory parameters of the groups were compared. Mortality risk factors were analyzed by logistic and Cox regression analyses. Result(s): A total of 75 patients with S. maltophilia infections were included. The mortality rate was 38.6% (n= 29). Advanced age (OR= 1.05, 95% CI= 1.012-1.085, p= 0.009), COVID-19 pneumonia (OR= 9.52, 95% CI= 1.255-72.223, p= 0.029), and presence of central venous catheter (CVC) (OR= 18.25, 95% CI= 2.187-152.323, p= 0.007) were risk factors for death. Conclusion(s): Physicians should be aware of the potential risk of S. maltophilia infections for mortality, particularly in patients with predefined risk factors such as advanced age, the presence of CVC, and COVID-19. Performing CVC care in accordance with infection prevention and control measures and timely removal of CVC may be beneficial in reducing deaths due to S. maltophilia infection.Copyright © 2023 Bilimsel Tip Yayinevi. All rights reserved.
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BACKGROUND: ROLE OF HEMOADSORBTION IN GRAM NEGATIVE SEPSIS AIM OF THE STUDY: TO SEE THE EFFICACY OF NOVEL ALTECO LPS ADSORBER IN A PATIENT WITH SEVERE GRAM NEGATIVE SEPTIC SHOCK METHODS: ALTECO LPS ADSORBER WAS USED IN A POST RENAL TRANSPLANT RECIPIENT WITH SEVERE SEPTIC SHOCK WITH ACTIVE COVID 19 INFECTION GRAM NEGATIVE SEPSIS ALONG WITH RENAL REPLACEMENT THERAPY USING PMMA FILTER. RESULT(S): SIGNIFICANT IMPROVEMENT IN HEMODYNAMICS, DECREASED VASOPRESSOR REQIUREMENT, RAPILDLY RECOVERED FROM SEPSIS AND SHOCK CONCLUSION(S): This case report highlights the efficacy of a new adsorptive therapy for the clearance of endotoxins in septic shock caused Gram negative bacterial infection. Early application of an endotoxin adsorber showed a reduction of vasopressor requirements, elevation of blood pressure, and a decrease in inflammatory markers. Endotoxin elimination has a significant effect on the ICU length of stay or ICU mortality.
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Background. Cefiderocol (CFDC) has a broad activity against Gram-negative (GN) pathogens. This study describes the usage of CFDC in US hospitals in patients with microbiology data during the initial phase of commercialization. Methods. This retrospective study included patients with laboratory-confirmed GN infections in US hospitals treated with CFDC consecutively for >=3 days between March 2020 to June 2021, as captured by Premier Healthcare data. This study describes the clinical characteristics, microbiology profile, CFDC usage, and post-CFDC initiation 14-day and 28-day in-hospital all-cause mortality (IH-ACM). Index culture was defined as the last day that culture sample(s) was taken before CFDC initiation or the first day the culture sample(s) was taken after CFDC initiation if no microbiology data before CFDC use was available. Index pathogens were all pathogens identified from the index culture(s). The index culture site was where the index culture was taken. Results. A total 187 in-patients received >=3 days CFDC and had >=1 microbiological result(s). The clinical characteristics of the patients and index culture results are provided in Table 1 and Table 2. About 60% of patients had at least one positive respiratory culture. The most frequent pathogens from the index culture were Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Acinetobacter baumannii. Nearly 75% of patients had one index pathogen, and 91% with one culture site. Almost 30% of patients had either one pathogen identified in multiple culture sites, or multiple pathogens from >=1 culture site. Crude 28-day IH-ACM for patients with any A. baumannii was 8.3% (95%CI: 0% -19.4%), any P. aeruginosa was 17.3% (95%CI: 9.9-24.8%), any S. maltophilia was 18.4%, (95%CI: 6.1%-44.0%) and any K. pneumoniae was 26.1% (95%CI: 8.1%-44.0%). Crude 28-day IH-ACM for patients with positive respiratory culture was five times higher in COVID patients than non-COVID patients. Conclusion. During the initial phase of CFDC availability, the most frequent pathogens treated using CFDC were non-fermenters, and the most frequent culture site was respiratory. IH-ACM appears to be affected by infection characteristics, especially COVID-19 status.
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Background. Secondary infections in patients receiving extracorporeal membrane oxygenation (ECMO) are difficult to identify as many signs traditionally associated with infection, such as temperature, are partially controlled by the ECMO circuit. This study analyzes the utility of procalcitonin (PCT) as a diagnostic marker in identifying secondary infections in patients receiving ECMO with influenza or COVID-19. Methods. A single center retrospective study was performed on patients receiving ECMO with underlying influenza or COVID-19 from November 2017 to October 2021. Patient demographics, time receiving ECMO, culture data, and PCT levels were extracted. The first PCT within three days of an infection designated positive was compared to negative values, PCT extracted from patients without an identified infection or any PCT 10 days after the most recent infection. Furthermore, PCT levels were compared by type of pathogen as well as site of infection via Mann-Whitney U tests. Results. 84 patients (77% males) met inclusion criteria with median age of 43 (interquartile range (IQR): 35-51). Median ECMO time was 416 hours (IQR: 232-824), with 64 (76%) of the patients admitted for COVID-19. A total of 276 (3.3 per patient) PCT were ordered during the study period. Of the 92 infections identified, 33 (36%) had an associated PCT value with 19 (58%) PCT collected on the day of positive culture, 10 (32%) within one day, and 4 (12%) collected two to three days after positive culture. There was no significant difference between median PCT value among the infection group (1.0 IQR: 0.40-1.19) compared to the non-infectious group (1.27 IQR: 0.47-4.26, p= 0.19), between Gram-positive and Gram-negative infections (1.09 IQR: 0.43-2.70 vs. 0.95 IQR: 0.4-1.29 p= 0.35) or between bloodstream infections and respiratory infections (1.3 IQR 0.45-2.70 vs. 0.55 IQR: 0.4-1.38, p=0.35). PCT does not decline after infection is identified (Figure 1). Procalcitonin Trends Conclusion. While PCT has been proposed as a potential diagnostic marker for secondary infections in patients receiving ECMO, this single center study did not demonstrate utility of PCT in identifying secondary infections. Furthermore, there was no association of PCT levels with either the site of infection or type of infectious organism. (Figure Presented).
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Background: ICU outcomes, especially related to infections, remains unclear in those with and without cirrhosis. With the emergence of resistant and fungal organisms, the changes in infection profiles over time is important to analyze. Method(s): Inpatients admitted to ICUs throughout 2015-2021 were analyzed. Cirrhosis was diagnosed using clinical and radiological features and were matched 1:1 by age, gender, and admission qSOFA to non-cirrhotic patients;COVID positive patients were excluded. Admission demographics and labs, hospital course were obtained for each patient. Comparisons were made between patients with and without cirrhosis and those who died/hospice versus not. Result(s): 1669 patients;833 cirrhosis and 836 non-cirrhosis patients were included, of which 456 (27%) died or were referred to hospice. Cirrhosis versus not comparison: Patients with cirrhosis had a higher rate of infection, positive cultures, abdominal infections, and bacteremia. They also had higher gram-positive and fungal infections with higher rate of VRE. Admission WBC, demographics, altered mental status, nosocomial or second infections or LOS were similar between cirrhosis/not groups.Death and hospice versus not comparison: 74% of patients who died had cirrhosis vs 41% of those who survived. Conversely, 41% out of 1213 patients who survived had cirrhosis (p<0.0001). People who died were more likely to have nosocomial infections, higher UTIs, bacteremia and respiratory infection and those with positive cultures, >1 organisms, VRE and MRSA isolation. Patients who died had higher LOS and all organ failures. On Logistic regression for death/hospice, cirrhosis (OR 4.0, p<0.0001), admission qSOFA (1.60, p<0.0001) and WBC (1.02, p=0.003), reasons for ICU (altered mental status 1.69, hypotension 1.79, renal support 2.77, respiratory failure 1.79 & CVA 1.96, all p<0.0001) with Infection (1.77, p<0.0001, >1 microbe isolated 1.86, p=0.05) were risk factors while skin and soft-tissue infections had a lower risk of death/hospice (0.39, p=0.02). Time trend in cirrhosis for infections: There was a significant decrease over time with positive culture and gram-negative infections and increase in fungal and gram-positive infections. Conclusion(s): Despite matching for demographics and qSOFA, patients with cirrhosis had a higher risk of death and organ failures, and were more likely to develop infections due to gram-positive and fungal infections with > 1 organisms and VRE, compared to those without cirrhosis. Patients who died were more likely to have cirrhosis, infections and higher qSOFA compared to those who survived. Time trends in cirrhosis showed lower rate of positive cultures and gram-negative infections and increase in fungal and gram-positive infections over time, which should encourage re-evaluation of diagnostic and prophylactic strategies in cirrhosis-related infections. (Figure Presented).
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Three new drugs, all based on messenger RNA or small interfering RNA technology, represented a major therapeutic advance in 2021. But the bigger picture is that most of the new authorisations that advanced patient care were adaptations of existing drugs. And that more than half of this year's new authorisations were not advances, and in fact about one-tenth represented a step backwards compared to existing options.
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Introduction: B cell maturation antigen (BCMA) is a novel target for T cell immunotherapy in MM including bispecific antibody (bsAb) and chimeric antigen receptor therapy (CAR-T). BCMA is critical for survival of the long-lived plasma cell, responsible for generation of protective antibodies. Impaired immune reconstitution, cytopenias, B cell aplasia and hypogammaglobinemia can compound preexisting MM-induced immunosuppression. In the case of bsAb, potential redirection/activation of T regulatory cells can create an immunosuppressive milieu. Herein, we describe the clinically relevant infectious complications observed across different BCMA-directed therapies used across multiple clinical trials at our center. Methods: Infections confirmed by microbiologic or histopathologic evidence were captured from the D1 C1 of bsAb and D 1 of lymphodepleting chemotherapy of autologous BCMA CAR-T therapies. The NCI CTCAE v5 was used to describe the site and grade of infections. Hypogammaglobinemia and severe hypogammaglobinemia were defined as ≤700 mg/dl and ≤400 mg /dl, respectively. Standard antimicrobial prophylaxis included herpes zoster prophylaxis for all MM patients with antibacterial (levofloxacin) / antifungal (fluconazole) during periods of neutropenia and IVIG supplementation as per the treating physician's discretion. PCP prophylaxis was prescribed to CAR T recipient per institutional guidelines. Descriptive statistics and comparisons were performed using two-sample t-test for continuous variables and chi-square goodness of fit test for categorical variables. Results: We identified 62 patients who received BCMA-directed bsAb (n=36) or CAR-T (n=26) between 2019-2021(table 1). The median age was 66 (range 48-84) years with % females and 14.8% of patients belonging to Black race. The median time to bsAb and CAR-T use from diagnosis were 6.6 (range 0.83-15.5) and 2.6 (range 0.35-14.4) years, respectively. The median lines of prior therapy were 6 (range 1-11) with BCMA CAR-T recipients receiving fewer prior lines of therapy (4 vs 6, p=<0.001). The baseline lymphocyte count was higher in the CAR-T (14.71 vs 0.84;p=<0.001). Baseline severe hypogammaglobulinemia and lymphopenia were present in 30% and 26.7% of all patients, respectively. Tocilizumab was used in 40.9% (bsAb -30.8% versus CAR-T 55.6%) patients for CRS. IVIG was used in 25% of patients. The median study duration for bsAb was 4 (range 0.03- 24) months across multiple dose levels. Median follow up among CAR-T recipients was 3.9 (range 0.3 - 22.3) months. Among recipients of bsAb, 41.2% of patients experienced at least one episode of infection vs. 23.1% with CAR-T (p=0.141). The cumulative incidence of infection with bsAb and CAR-T were 22 and 8, respectively. The spectrum of infections with bsAb was predominantly bacterial (64.3% While gram negative infection (Escherichia coli and Klebsiella pneumoniae bacteremia, Proteus mirabilus and Psuedomonas aeroginosa urinary tract infections) were seen in 6 patients, skin infection including cellulitis occurred in 4 patients, with 1 case of necrotizing cellulitis. Bacteremia with rare opportunistic pathogens - Rhizobium radiobacter and recurrent Ochrobacterium anthropi were also observed . Viral infections included rhinovirus, cytomegalovirus, and parvovirus B19 reactivation, and COVID-19. About 50% of infections were ≥ grade 3 with 2 grade 5 events (Pseudomonas aeruginosa bacteremia and COVID-19). In the CAR-T group, we observed more viral infections (66.7% vs 35.7%;p=0.028) and fewer bacterial infections (33.3% vs 64.3%;p=0.028) . Common viral infections included rhinovirus, RSV, and herpes simplex virus reactivation. In this group 25% of infections were ≥grade 3. Conclusion: BCMA-targeted therapies seem to be associated with clinically significant bacterial and viral infections. Repetitive dosing with bsAb therapies could be the reason for the propensity to serious bacterial infections compared to CAR-T recipients and may need novel prophylaxis strategies. (Figure Presented).
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Case report-IntroductionBacterial and fungal infections are recognised complications of viral pneumonia, particularly in patients who are critically ill. We describe a case of fungal sacroiliitis complicating severe COVID-19 pneumonia following a prolonged intensive care unit (ICU) admission.Candida albicans sacroilitis is a rarely reported infection with few case reports in the literature. Candida osteoarticular infections can present as septic arthritis, with knee involvement in 75% of cases, or osteomyelitis. The latter presentation differs based on age-vertebral involvement (51%) is more common in adults while children are more likely to present with infection in the long bones, ribs, or sternum.Case report-Case descriptionA 48-year-old Afro-Caribbean gentleman with a history of hypertension and obesity was admitted to the ICU with clinical, laboratory and radiographic features of COVID-19 infection despite persistently negative swabs. Whilst in ICU he required mechanical ventilation. His stay was further complicated by multiple infections, pulmonary emboli, and the presence of a cavitating lesion in the left lung. Cultures from bronchoalveolar lavage and a central venous catheter line grew Serratia Mascense, candida glabrata and pseudomonas were isolated from his urine. He was treated with multiple antibiotics including meropenem, tazocin, ceftazidime and avibactam.After 61 days in the ICU he was transferred to the ward. He developed severe pain in his right hip which was worse on movement. This was followed by urinary incontinence and sensory deficit in the right L2/L3 dermatome. He underwent magnetic resonance imaging (MRI) of his spine and sacroiliac joints which showed right sided sacroiliitis and oedema around the iliopsoas muscle. He was started on vancomycin, later changed to ceftazidime avibactam and metronidazole. An echocardiogram did not show any vegetations. He underwent a biopsy of his sacroiliac joints which confirmed the presence of leucocytes, extended cultures yielded candida albicans in one out of two biopsy specimens.Considering ongoing pyrexia, pain and inflammatory markers, intravenous fluconazole was added to his antibiotic regimen which resulted in a marked improvement in mobility. After four weeks, ceftazidime, metronidazole and avibactam were stopped, and fluconazole was administered as oral tablets. 6 days later he became febrile and IV fluconazole was restarted.A repeat chest CT showed resolution of the cavity but ongoing changes suggestive of organising pneumonia. A repeat MRI of the sacroiliac joints revealed minor improvement. Intravenous Fluconazole was continued for a total of 8 weeks and was changed to tablets for complete a total of 12 weeks.Case report-DiscussionThis is a severe case of COVID-19 infection who despite 9 negative PCR tests, on day 53, had positive IgG for SARS-CoV-2 infection, confirming our clinical suspicion. Particularly in the ICU setting, individuals are approximately ten times more likely to have secondary bacterial/fungal infections with more frequent detection of multidrug-resistant Gram-negative pathogens.This case highlights several difficulties. Urine cultures had confirmed candida albicans, likely to be related to catheter related urinary tract infections, and a possible source for our patient but also a resistant pseudomonas aeruginosa species. Furthermore, cultures were positive for Serratia Mascense, candida glabrata. He had also already been treated with prolonged, broad spectrum antimicrobial treatment. Considering this, establishing the aetiology of the septic sacroiliitis was challenging. The rarity of candida sacroiliitis and presence of the organism in just one specimen made this more difficult. This led to the decision of a repeat sacroiliac biopsy to supply sufficient samples for further microbial analyses such as 16S, 18S and mycobacteria culture, all of which were negative.He became febrile after the discontinuation of antimicrobials and a switch to oral fluconazole therapy. He was extensively re-investigated and despite resolution of t e lung cavity, there were changes which could have been consistent with an organising pneumonia. At this point he was neutropenic, mildly eosinophilic, and therefore a drug reaction was also considered.Repeat MRI revealed resolving muscle inflammation and minimal change at the bone site, with erosions and possible reactive bone marrow oedema. Following discussion with microbiology the decision was made to persist with intravenous Fluconazole. He continued to improve, and his inflammatory markers normalised after 8 weeks of treatment. Prednisolone was started for COVID-19 related pneumonitis. Long-term antifungal treatment is advisable, and we aim to complete 12 weeks of treatment.Case report-Key learning points Patients with SARS-CoV-2 infection, particularly those requiring ICU admission were at risk of developing superinfections with multidrug-resistant Gram-negative bacteria or fungal infections.Candida albicans sacroiliitis is rare therefore early aspiration/biopsy is essential for the management.Longer treatment is needed in osteoarticular candida infections, even up to 6 or 12 months, therefor long-term close monitoring of this patients is essential.The utility and timing of reimaging patients following such infections is still unclearClose multidisciplinary and interdisciplinary team collaboration is essential in the management of this complex patients.