scholarly journals 297. Infectious Complications Associated with Tocilizumab Use in Patients Infected with SARS-CoV-2 at a Mid-Atlantic Hospital Consortium

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S256-S256
Author(s):  
Kristen R Kent ◽  
Nellie Darling ◽  
Xue Geng ◽  
Gavin Clark ◽  
Marybeth Kazanas ◽  
...  

Abstract Background The IL-6 inhibitor Tocilizumab (TOCI) has been associated with infections in 5-8% of patients with Rheumatoid Arthritis. TOCI has now been recommended as a treatment option for select patients with COVID-19; however, the risk of infection in this patient population is yet to be determined. Methods We performed a retrospective chart review of patients diagnosed with COVID-19 and admitted to MedStar hospitals within the D.C./Baltimore corridor from 03/01/2020 to 12/31/2020. We identified patients who had positive culture data within 30 days of administration of TOCI-based regimens and analyzed clinical characteristics and outcomes. Univariate analyses (Wilcoxon, T-test, Chi-Square, Fisher’s Exact) were used to compare these outcome variables between patients who had post-treatment infections and those who did not. Results A total of 220 patients received TOCI-based regimens; 16% (N=36) of patients developed positive cultures within 30 days of treatment. Of the 99 cultures, 50% were gram positive (N=49), 38% were gram negative (N=38), 10% were Candida spp. (N=10), and 2% were anaerobic organisms (N=2). Only 9% (8/87) of the gram positive and gram negative organisms were MDROs. Bloodstream infections were the most common and accounted for 58.4% of all infections. Length of stay (LOS) was approximately twice as long in those with post-treatment infections (26 days) compared to those without infections (14 days, p< 0.001). Although the mortality rate was higher in patients with infections after TOCI-based treatment compared to patients with no post-treatment infection (47% vs 31% respectively), this did not reach statistical significance (p=0.09). Moreover, there was no significant difference in the infection rate of patients treated with TOCI alone compared to TOCI and Dexamethasone (16.6% vs. 13.3%, p=0.99). No cases of invasive Aspergillosis were observed. Conclusion Tocilizumab treatment in patients with COVID-19 may predispose patients to an increased risk of infection which is associated with a prolonged LOS and possibly higher mortality. We observed a two-fold increase in infections in COVID-19 patients compared to other patient groups receiving this treatment. Disclosures Princy N. Kumar, MD, AMGEN (Other Financial or Material Support, Honoraria)Eli Lilly (Grant/Research Support)Gilead (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)GSK (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)Merck & Co., Inc. (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3752-3752
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Fauzia Rana ◽  
Marwan Shaikh

Abstract Heparin-induced thrombocytopenia (HIT) is caused by antibodies targeting platelet factor 4 (PF4)/heparin complexes. The immune response leading to HIT remains perplexing with many paradoxes. Unlike other drug induced reactions, anti-PF4/heparin antibody generation does not follow the classic immunologic response. As Greinacher and colleagues have shown, the primary immune response lacks IgM precedence and class switching, and heparin-induced antibodies can induce HIT by day 5 in heparin-naïve patients.Continued exposure to heparin also is puzzling with a weak or declining secondary immune response. Research by Krauel and colleagues suggests that that there is close interplay among infection, PF4 and the immune system. In 2010 they demonstrated that human and murine PF4 bind to Gram positive (S.aureus, S.pneumoniae, L.monocytogenes) and Gram negative (E.coli, N.meningitidis) bacteria in vitro, with bacterial surfaces acting as polyanions. High dose heparin inhibited this binding and anti-PF4/heparin antibodies from patients with HIT reacted with these PF4/bacterial complexes (S. aureus and E. coli). Using a murine model, they went on to show that polymicrobial sepsis in the absence of heparin led to antibody generation. In a separate study, Krauel and colleagues also showed that PF4 binds specifically to the lipid A component of Gram negative bacteria. In this analysis, we report on anti-PF4/heparin antibody levels in groups of patients hospitalized for sepsis, as compared to a control group without sepsis. We examined 200 patients with sepsis, retrospectively identified, from a hospital database of anti-PF4/heparin testing done in medical inpatients with thrombocytopenia but low pretest probability of HIT. This included patients with bacteremia (57), fungemia (7) and sepsis without septicemia (136). For comparison, data from 50 patients without sepsis during the same time period was used. Inclusion criteria for all groups were age 18 years and older and antibody testing within 4 days of admission. Exclusion criteria were diagnosis of HIT or heparin allergy, prior hospitalization or heparin exposure within 90 days of admission, cardiopulmonary bypass or orthopedic surgery within 6 months, hemodialysis, active or past malignancy, antiphospholipid syndrome, autoimmune disease or immunosuppressive therapy. All patients studied were on subcutaneous heparin at prophylactic doses only (i.e. no intravenous use, no therapeutic anticoagulation). UFH use predominated with prevalence of >85% in all groups. Testing was done using a commercially available standardized solid phase enzyme-linked immunoassay (EIA) to detect antibodies (IgG/IgA/IgM) directed against PF4 complexed with polyvinylsulfonate (Genetic Testing Institute, Wisconsin). All assays were performed in the central hospital laboratory according to manufacturer's specifications and measured in optical density (OD) units. The data sets demonstrated continuous unimodal distribution with high OD outliers, indicative of varying immune responses along a continuum. Statistical significance was calculated using independent t-testing with p-value set at 0.05 for significance. Results showed that patients hospitalized with sepsis have higher anti-PF4/heparin antibody levels. Both patients with bacteremia, and sepsis without bacteremia, had significantly higher OD than patients without sepsis (p<0.05). There was no significant difference between Gram negative and Gram positive bacteremia and antibody levels. This suggests that bacterial cell wall components of both classes have similar antigenicity. Interestingly, patients with fungemia had much lower antibody levels compared to bacteremia and sepsis. Despite the small sample size for fungemia, this difference trended strongly towards statistical significance (p=0.05). The threshold for a positive EIA is currently established at OD>0.400, a value based on sensitivity and set by the manufacturer. When the prevalence of a positive EIA was assessed, 16% patients with sepsis and bacteremia tested positive compared to 4% in the control group. In summary, there is an increased prevalence of anti-PF4/heparin antibodies in patients hospitalized with bacterial but not fungal sepsis. These results support the theory that bacterial infection has a role to play in preimmunization leading to anti-PF4/heparin antibody generation. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S602-S603
Author(s):  
Pia Cumagun ◽  
Jeremy Meeder ◽  
Derek Moates ◽  
Hannah Pierce ◽  
Todd P McCarty ◽  
...  

Abstract Background The GenMark Dx ePlex BCID Gram-Negative (GN) panel utilizes electrowetting technology to detect the most common causes of GN bacteremia (21 targets) and 6 antimicrobial resistance (AMR) genes from positive blood culture (BC) bottles. Rapid detection of extended spectrum β-lactamases (ESBL: CTX-M & carbapenemases: KPC, NDM, IMP, VIM, OXA 23/48), and highly resistant bacteria such as S. maltophilia should enable early optimization of antimicrobial therapy. Methods In this prospective study, aliquots of positive BC bottles with GN bacteria detected on Gram stain (GS) (n=108) received standard of care (SOC) culture and antimicrobial susceptibility testing (AST). Additionally, samples were evaluated with the BCID-GN panel but only SOC results were reported in the EMR and available to inform clinical decisions. Chart reviews were performed to evaluate the impact of the BCID-GN panel on the time to organism identification, AST results, and optimization of antimicrobial therapy. Results A total of 108 patients are included in the analysis (Table 1). Escherichia coli was the most common bacteria identified followed by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter species (Table 2). There were 11 (10.2%) polymicrobial bacteremias. Repeat BCs were obtained in 68 (63%) patients of which 13 (19%) were persistently positive. Eight (7%) patients had evidence of additional gram-positive (GP) pathogens. Organism identification occurred 26.7 hours faster than culture. In conjunction with GS, negative pan-GP marker data could have helped providers make the decision to remove GP antibiotic coverage in 63 (58%) patients. Narrowing from empiric meropenem could have occurred in 5 patients. Of 10 individuals infected with resistant isolates (1 S. maltophilia, 1 OXA 23/48, and 8 CTX-M) empiric therapy was ineffective in 4 (40%) cases. Optimization of antimicrobial therapy for 9 (8.3%) patients could have occurred an average of 52.4 hours earlier than standard methods. Table 1. Patient demographics and co-morbidities. Table 2. Gram-negative bacteria frequency. Conclusion The BCID-GN panel enabled earlier time to optimal treatment of highly resistant bacteria as well as multiple opportunities for narrowing gram negative spectrum and a higher degree of certainty in cessation of broad-spectrum gram-positive antibiotics Disclosures Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Sixto M. Leal, Jr., MD, PhD, Abnova (Grant/Research Support)AltImmune (Grant/Research Support)Amplyx Pharmaceuticals (Grant/Research Support)Astellas Pharmaceuticals (Grant/Research Support)CNINE Dx (Grant/Research Support)GenMark Diagnostics (Grant/Research Support, Other Financial or Material Support, Honoraria- Research Presentation)IHMA (Grant/Research Support)IMMY Dx (Grant/Research Support)JMI/Sentry (Grant/Research Support)mFluiDx Dx (Grant/Research Support)SpeeDx Dx (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)


Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3550
Author(s):  
Aerin Choi ◽  
Kyung-Hyeon Yoo ◽  
Seog-Young Yoon ◽  
Bong-Soo Park ◽  
In-Ryoung Kim ◽  
...  

Self-adhesive resins (SARs) contain adhesives, which simplify the procedures of resin application, and primers, which provide sufficient bonding ability. In this study, mesoporous bioactive glass nanoparticles (MBN) were added to a SAR to easily improve the physical properties and remineralization ability. The experimental resins comprised 1%, 3%, and 5% MBN mixed in Ortho Connect Flow (GC Corp, Tokyo, Japan). As the MBN content in the SAR increased, the microhardness increased, and a statistically significant difference was observed between the cases of 1% and 5% MBN addition. Shear bond strength increased for 1% and 3% MBN samples and decreased for 5% MBN. The addition of MBN indicated a statistically significant antibacterial effect on both gram-negative and gram-positive bacteria. The anti-demineralization experiment showed that the remineralization length increased with the MBN content of the sample. Through the above results, we found that SAR containing MBN has antibacterial and remineralization effects. Thus, by adding MBN to the SAR, we investigated the possibility of orthodontic resin development, wherein the strength is enhanced and the drawbacks of the conventional SAR addressed.


2021 ◽  
pp. 112972982199022
Author(s):  
Salvatore Mandolfo ◽  
Adriano Anesi ◽  
Vanina Rognoni

Recent reports have shown an increase in the rate of Gram-negative bacteremia in several settings, including catheter-related bloodstream infections (CRBSI). To analyze if the epidemiology of CRBSI is also changing in hemodialysis patients, we revisited the etiology of CRBSIs in our renal unit over 8 years. During the observed periods, 149 episodes of CRBSIs were reported and the CRBSI incidence rate, ranged between 0.67 and 0.82 episodes/1000 tCVC days. Of these 149 episodes, 84 (56.3%) were due to Gram-positive bacteria, 62 (41.6%) to Gram-negative bacteria, and 3 (2.1%) to polymicrobial flora, no episodes of fungi were found. There was a trend, but not statistically significative, increase over time in the number of Gram-negative CRBSIs among the total CRBSIs, rising from 37.8% in the first period to 41.2% in the second period and to 44.3% in the last period, with a parallel decrease in the percentage of Gram-positive CRBSIs (from 59.5% to 56.9% and subsequently to 54.1%). Between Gram-negative, we reported an intensification of CRBSI due to Enterobacterales, particularly Escherichia coli. Among the Gram-negative, we have isolated germs rarely reported in the literature, such as Burkholderia cepacia, Pantoea agglomerans, and Rhizobium radiobacter. Regarding Gram-positive bacteria, a triplicate incidence of Staphylococcus aureus was reported with MRSA accounting for 42% in the third period. Among the Gram-positive bacteria, we reported two episodes of Kocuria kristinae and two of Bacillus spp. Our data demonstrated that the epidemiology of CRBSI in the same center, will change over time and Gram-negative strains are an increasing cause of CRBSI. The limitation of the present report is that statistical significance has not been reached, probably due to the limited number of CRBSI. New bacteria, both Gram-negative and Gram-positive, are emerging. Collaboration with the Microbiology Department appears essential to an appropriate diagnosis.


Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 436
Author(s):  
Giovanni Parente ◽  
Tommaso Gargano ◽  
Stefania Pavia ◽  
Chiara Cordola ◽  
Marzia Vastano ◽  
...  

Pyelonephritis (PN) represents an important cause of morbidity in the pediatric population, especially in uropathic patients. The aim of the study is to demonstrate differences between PNs of uropathic patients and PNs acquired in community in terms of uropathogens involved and antibiotic sensitivity; moreover, to identify a proper empiric therapeutic strategy. A retrospective study was conducted on antibiograms on urine cultures from PNs in vesicoureteral reflux (VUR) patients admitted to pediatric surgery department and from PNs in not VUR patients admitted to Pediatric Emergency Unit between 2010 and 2020. We recorded 58 PNs in 33 patients affected by VUR and 112 PNs in the not VUR group. The mean age of not VUR patients at the PN episode was 1.3 ± 2.6 years (range: 20 days of life–3 years), and almost all the urine cultures, 111 (99.1%), isolated Gram-negative bacteria and rarely, 1 (0.9%), Gram-positive bacteria. The Gram-negative uropathogens isolated were Escherichia coli (97%), Proteus mirabilis (2%), and Klebsiella spp. (1%). The only Gram-positive bacteria isolated was an Enterococcus faecalis. As regards the antibiograms, 96% of not VUR PNs responded to beta-lactams, 99% to aminoglycosides, and 80% to sulfonamides. For the VUR group, mean age was 3.0 years ± 3.0 years (range: 9 days of life–11 years) and mean number of episodes per patient was 2.0 ± 1.0 (range: 1–5); 83% of PNs were by Gram-negatives bacteria vs. 17% by Gram-positive: the most important Gram-negative bacteria were Pseudomonas aeruginosa (44%), Escherichia coli (27%), and Klebsiella spp. (12%), while Enterococcus spp. determined 90% of Gram-positive UTIs. Regimen ampicillin/ceftazidime (success rate: 72.0%) was compared to ampicillin/amikacin (success rate of 83.0%): no statistically significant difference was found (p = 0.09). The pathogens of PNs in uropathic patients are different from those of community-acquired PNs, and clinicians should be aware of their peculiar antibiotic susceptibility. An empiric therapy based on the association ampicillin + ceftazidime is therefore suggested.


2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
B Edwards ◽  
A Zolnourian ◽  
D Bulters

Abstract Introduction External ventricular drains (EVDs) are commonly used in the management of acute hydrocephalus after subarachnoid haemorrhage (SAH). Infection is the most common complication. There remains controversy over whether frequent sampling is associated with increased risk of infection. Method Two cohorts of patients requiring EVD after SAH were retrospectively analysed for suspected and proven CSF infection. The first clinical cohort was of 50 consecutive patients with twice weekly sampling. The second group had alternate daily sampling as part of a prospective research study. Results Female to male ratio were (32:18) and (29:15) in clinical vs research group respectively. Average age of both groups was 59. Average length of treatment with EVD in both groups was 10 days. 16/50 (32%) patients had a suspected infection vs 13/44 (30%) and 8/50 (16%) had a proven infection compared to 6/44 (14%) in clinical and research groups, respectively. There was no statistically significant difference between the two groups (suspected infections p = 0.7 and proven infections p = 0.7) Conclusions Increased rates in CSF sampling in the research cohort did not result in higher rates of CSF infection. This suggests that rate of sampling, if done following a strict protocol, is not associated with increased risk of infection.


2008 ◽  
Vol 65 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Radojica Stolic ◽  
Goran Trajkovic ◽  
Vladan Peric ◽  
Aleksandar Jovanovic ◽  
Dragica Stolic ◽  
...  

Backgraund/Aim. Hemodialysis catheter, as an integral part of hemodialysis, is a catheter placed into the jugular, subclavian and femoral vein. The most common catheter-related complications are infections and thrombosis. The aim of the study was to analyze the prevalence of complications associated with differently inserted central-vein catheters for hemodialysis. Methods. The study was organized as a prospective examination during the period from December 2003 to November 2006, and included all patients who needed an active depuration by hemodialysis, hospitalized at the Clinical Center Kragujevac. The subject of the study were 464 centralvein catheters inserted during the mentioned period and there were recorded all complications related to the placement and usage of catheters. Results. The largest percent of inserted catheters was into the femoral vein ? 403 (86.8%), significantly less into the jugular vein ? 42 (9.2%), while into the subclavian vein there were placed only 19 catheters (4%). The average of femoral catheter functioning was 17 catheter days, in jugular catheters it was 17.3 days while the subclavian catheters had an average rate of functioning of 25.9 catheter days; there was found a statistically significant difference regarding the duration of functioning (p = 0.03). By microbe colonization of smear culture of the skin at the catheter insertion site, in clinically present suspicion of catheter infection, there was obtained a positive finding in 5.5% of catheters placed into the femoral vein and 7.1% of catheters instilled into the jugular vein, of which Staphylococcus aureus was the most important bacterial type, without statistically significant difference (p = 0.51). Haemoculture, done when there was a suspicion of bacteriemia, was positive in 3.7% of the patients with femoral and 4.8% with jugular catheters; Staphylococcus aureus was the most common bacteria type, but there was no statistically significant difference (p = 0.65). Colonizing the smears of the cut catheter tops, there was found a positive finding in 8.9% of femoral and 4.7% of jugular catheters in which the mentioned type of staphylococcal bacteria was prevalent, without statistically significant difference (p = 0.82). In 77% of femoral, 71.4% of jugular and 68.4% of subclavian catheters, there were no complications associated with insertion and manipulation of catheters for hemodialysis and the difference was at the limits of statistical significance (p = 0.06). Conclusion. Unconvincing rate of infections and a smaller percent of serious complications associated with the placement and use of central vein catheters instilled into the femoral vein, indicate that personal experience is sufficient recommendation to convince us that femoral vein does not represent a region with an increased risk for insertion of hemodialysis catheters.


2021 ◽  
Vol 13 (1) ◽  
pp. 106-112
Author(s):  
Sri Kasmiyati ◽  
Elizabeth Betty Elok Kristiani ◽  
Maria Marina Herawati ◽  
Andreas Binar Aji Sukmana

The medicinal plant-derived bioactive compounds have a potential for many biological activities, including antimicrobial activity. Artemisia cina is a medicinal plant from the Compositae family with the potential of having antitumor, antifungal, and antibacterial activity. This study aimed to determine the antibacterial activity and the flavonoid content of A. Cina’s ethyl acetate extract. Plants samples were extracted by ethyl acetate maceration method. Antibacterial activity was tested against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) by a disk diffusion method using 25, 50, and 100 mg/l extract concentrations. The flavonoid contents (quercetin and kaempferol) were measured using High-Performance Liquid Chromatography. The extracts of diploid and polyploid A. cina displayed some antibacterial activity, with the Gram-negative bacteria being more resistant than the Gram-positive counterpart. However, no significant difference was observed between the diploid and polyploid extracts. As for the flavonoid content, the highest quercetin content (0.5501 mg/ml) was found in the polyploid A. cina (J), while the highest kaempferol content (0.5818 mg/ml) was observed in the diploid A. cina (KJT). Although A. cina is widely grown in Indonesia, compared to other Artemisia species, A. cina has not been widely studied, especially its antibacterial  potential and in related to its flavonoid content and the use of ethyl acetate as the extraction solvent.  This study reveals the potential of A. cina as a natural antibacterial agent. 


2005 ◽  
Vol 52 (3) ◽  
pp. 33-37
Author(s):  
Ivana Cirkovic ◽  
Vera Mijac ◽  
Milena Svabic-Vlahovic ◽  
S. Dukic ◽  
I. Ilic ◽  
...  

Objectives: The application of Central Venous Catheters (CVC) is associated with increased risk of microbial colonization and infection. The aim of present study was to assess the frequency of pathogens colonizing CVC and to determine their susceptibility pattern to various antimicrobial agents. Materials and methods: A total of 253 samples of CVC from intensive care units (ICU) patients were received for culture during 2003. All microorganisms were identified by standard microbiological methods and the susceptibility to antimicrobial agents was determined according to NCCLS recommendations. Results: A total of 184 (72.7%) cultures were positive and 223 pathogens were isolated. Coagulase negative staphylococci (CNS) were the dominant isolates (24.7%), followed by Enterobacter spp. (12.1%), Pseudomonas spp. (11.7%), Enterococcus spp. (9.9%), Klebsiella spp. (8.6%), Candida spp. (7.6%), Acinetobacter spp. (7.6%), other Gram negative nonfermentative bacilli (5.8%), Serratia spp. (4.5%), Staphylococcus aureus (2.6%), Proteus mirabilis (2.2%), E. coli (1.8%) and Citrobacter spp. (0.9%). Meropenem (84.5%) and vancomycin (100%) remain the most effective antimicrobial agents against Gram negative and Gram positive bacteria, respectively. Conclusion: Gram negative bacilli and CNS are the commonest microorganisms colonizing CVC from ICU patients. The increasing resistance of the bacteria to antimicrobial agents is the major problem in spite of restricted policy of using antimicrobial agents in ICU.


2019 ◽  
Vol 7 (1) ◽  
pp. 88-91 ◽  
Author(s):  
Valentina Tofiloska ◽  
Maria Krstevska ◽  
Ana Daneva-Markova ◽  
Viktorija Jovanovska

BACKGROUND: Postmenopausis is a period that begins one year after the last menstrual period. Abnormal uterine bleeding could be of different origins. AIM: This study aimed to determine the association of serum estrogen hormone levels and obesity with the occurrence of endometrial bleeding in post-menopausal women. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics-Skopje, divided into two groups: control and study. The control group consisted of 40 postmenopausal patients without endometrial bleeding, hospitalised and operated due to urogenital pathology. The study group consisted of 80 patients with endometrial bleeding who were divided into three subgroups according to the thickness of the endometrium: from 5-8 mm, 8-11 mm and above 11 mm. In all subjects, estradiol and BMI was determined. RESULTS: Estradiol levels were statistically higher in the study group compared to control while statistically significant difference among the three subgroups according to the thickness of the endometrium about the levels of estradiol in blood is not found. About BMI, the results showed that there was no statistical significance between the two examined groups. CONCLUSION: Patients with endometrial bleeding have increased levels of estradiol and are at increased risk of endometrial cancer about controls, the likelihood of endometrial cancer significantly increases by 1,108 times.


Sign in / Sign up

Export Citation Format

Share Document