Negative Blood Cultures Research Articles

Генетические аспекты неинфекционного эндокардита у пациентов с антифосфолипидным синдромом

Introduction. Antiphospholipid syndrome (APS) is an autoimmune thrombophilia in which patients with clinical criteria for recurrent arterial and venous thrombosis and/or pregnancy failure show positive laboratory results for the presence of antiphospholipid antibodies (aPL). The genetic predisposition to non-infectious endocarditis (NIE) in patients with APS remains a complex and poorly understood problem. Aim. Revealing of possible associations between polymorphisms of candidate genes and non-infectious endocarditis in patients with APS, as well as the development of possible thromboembolic complications. Materials and methods. The study involved 35 patients aged 43.0 ± 13.9 years. At the same time, the main signs characterizing NIE in APS were negative blood culture, normothermia, and the absence of obvious echoscopic signs of infection (thickening and induration calcification of the valve leaflets, minimal regurgitation). Polymorphisms of 18 genes were studied as possible molecular genetic markers for the development and/or protection of NIE in 35 patients with APS: the primary disorder was diagnosed in 15 patients (18.5%), secondary – in 20 patients with autoimmune patho¬logy (24.7%). Results. For the first time, for polymorphisms rs6025 (1691 G>A) of the F5 gene, 4а/4b of the NOS3 gene, rs1800795 of the IL6 gene, rs1805087 (2756 A>G) of the MTR gene, a significant association with the development of vegetations on the valvular heart apparatus in APS was revealed. Two polymorphisms, rs1126643 (807 C>T) of the ITGA2 gene and rs1799889 (-675 5G>4G) of the PAI1 gene (SERPINE1), were found to be associated with thromboembolic complications (acute cerebrovascular accident) in NIE. Conclusion. It is reasonable to perform genotyping of some single nucleotide polymorphisms in patients with APS.

Double valve infective endocarditis due to Capnocytophaga canimorsus

Infective endocarditis caused by Capnocytophaga canimorsus, a commensal organism commonly found in dog saliva, is uncommon. We describe a case of a 76-year-old male with native aortic and mitral valve endocarditis with ventricular-atrial fistulization due to Capnocytophaga canimorsus. He was successfully treated with intravenous antimicrobials and surgery. Capnocytophaga canimorsus should be considered as a cause of infective endocarditis in patients with negative blood cultures, in asplenic patients, and in those with appropriate exposures.

Post-COVID multisystem inflammatory syndrome in adults: a study from a tertiary care hospital in south India.

There are limited data from India on the post-COVID multisystem inflammatory syndrome in adults (MIS-A). The objective of the present study was to evaluate the clinical profile of patients with MIS-A admitted to a tertiary care centre in southern India. This single-centre retrospective study was conducted from November 2020 to July 2021, and included patients aged >18 yr admitted to the hospital as per the inclusion and exclusion criteria. Nine patients (5 male, mean age 40±13 yr) met the criteria for MIS-A. Five patients had proven COVID-19 infection or contact history 36.8±11.8 days back. All patients were positive for SARS-CoV-2 IgG antibody, negative for COVID-19 PCR, and had negative blood, urine and sputum cultures. All patients had fever and gastrointestinal (GI) symptoms, and five patients had left ventricular dysfunction. All patients had neutrophilic leucocytosis at presentation and elevated biomarkers such as C-reactive protein serum procalcitonin, D-dimer and ferritin. The majority of the patients (7/9 i.e. 77.78%) were treated with intravenous hydrocortisone (50-100 mg q6h-q8h). Six patients recovered completely whereas three patients expired. Fever and GI symptoms were the most common presentation of MIS-A. Elevated serum procalcitonin may not be useful in differentiating bacterial sepsis from MIS-A. Most patients responded to corticosteroids.

Co-infections in patients with COVID: A case series.

Dear Editor, Respiratory viruses may be associated with varying rates of microbial co-infections. There is previous evidence to show lack of bacterial co-infections following Middle East respiratory syndrome and only a small incidence with the severe acute respiratory syndrome-associated coronavirus-1.[1] We are reporting three patients of severe acute respiratory illness (fever and bilateral pneumonitis) with laboratory-confirmed (RT-PCR) COVID, who developed microbial co-infections. All had received protocolized pharmacological therapy including remdesivir/oral hydroxychloroquine, subcutaneous low molecular weight heparin, intravenous dexamethasone, prophylactic antibiotics as well as vitamin C and oral zinc supplementation in the ICU. All three patients had presented with raised total leucocytic count (TLC: 19,600; 23,600; and 23,400/mm3, respectively) in contrast to the expected immunosuppression and decreased TLC associated with COVID. The microbial organisms detected in the patients upon blood culture included Enterococcus faecium (sensitive to vancomycin, teicoplanin, and linezolid); Staphylococcus xylosus (resistant to erythromycin, ceftriaxone, ciprofloxacin, and tetracycline; sensitive to teicoplanin, vancomycin, linezolid, and cotrimoxazole) and non-albicans candida without any bacterial growth, respectively. An adequate response was seen with vancomycin in a patient with E. faecium, and with teicoplanin to S. xylosus as evidenced by an improvement in clinical condition, fall in TLC, and negative repeat blood cultures. The patient with candidemia, however, succumbed to COVID-induced acute respiratory distress syndrome within next couple of days. A systematic review showed a 14% incidence of laboratory-confirmed bacterial co-infection among the patients with COVID admitted to ICU.[1] Thus, our findings help to emphasize that co-infections in patients with COVID are a clinical problem. The bacterial organisms detected by us are not commonly encountered otherwise. E. faecium was reported as the least common of co-infections in COVID with an incidence of 1/3834 patients.[1] Within the Enterococcus species, only 10% of infections are constituted by E. faecium.[2] It is more likely to be seen in immunosuppressed, elderly, critically ill, those on mechanical ventilation or long-term antibiotic therapy, for causing infections and multi-systemic manifestations.[23] S. xylosus-induced sepsis also presents an uncommon occurrence. The organism is usually incriminated in infections among animals, with very few case reports amongst humans. It is a normal commensal on the skin and mucosa and becomes a cause of infections either as part of nosocomial pathology or in immunosuppressed individuals.[4] Lastly, invasive candidemia reported in the third case by us is also known to have a predisposition for immunosuppressed patients. Thus, it is possible that the microbial co-infections in COVID are preferential of flora that thrives in immunocompromised patients. It is interesting to note that all of these patients with co-infections during COVID illness presented with raised TLC, even though the neutrophil–lymphocyte ratio was high and suggestive of COVID. There are previous data to show that raised TLC in COVID is associated with a poor prognosis.[5] Thus, surveillance for microbial co-infections, even uncommon ones, is required in patients with COVID and the role of raised TLC remains pertinent for the same. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Severe aortic insufficiency secondary to infective endocarditis in a patient with intraventricular septal defect, case report

Background: infective endocarditis is a septic condition predominantly of bacterial origin, although there is a fungal etiology of the native valvular endothelium of the heart, it is a disease associated with high mortality and complications, despite advances in its approach, its incidence has not decreased in the last 30 years. Case report: 30-year-old black female patient, housewife, with a personal history of intraventricular septal defect. She went to the on-call department for presenting high fever at any time of the day accompanied by chills, with joint pain. She had undergone a curettage due to the presence of a fetal ovum. Three days prior to this, she had a fever of 38 degrees Celsius with no specific time of day, accompanied by chills, which was easily relieved with sodium metamizole. The fever persisted daily, which led to several hospital admissions, after which she was discharged home with no diagnostic cause. She was readmitted due to a chronic febrile syndrome, to which joint pain was added. Medulogram was performed and was not useful, suggesting iliac crest biopsy to rule out anarco-proliferative processes, and antimicrobials were not administered during this time. Conclusions: infective endocarditis on native valves with negative blood cultures remains a challenge, despite medical advances in recent decades, and due to demographic changes of patients and the disease, it remains a complex pathology with high morbidity and mortality

What Does 16S rRNA Gene-Targeted Next Generation Sequencing Contribute to the Study of Infective Endocarditis in Heart-Valve Tissue?

Infective endocarditis (IE) is a severe and life-threatening disease. Identification of infectious etiology is essential for establishing the appropriate antimicrobial treatment and decreasing mortality. The aim of this study was to explore the potential utility of metataxonomics for improving microbiological diagnosis of IE. Here, next-generation sequencing (NGS) of the V3–V4 region of the 16S rRNA gene was performed in 27 heart valve tissues (18 natives, 5 intravascular devices, and 4 prosthetics) from 27 patients diagnosed with IE (4 of them with negative blood cultures). Metataxonomics matched with conventional diagnostic techniques in 24/27 cases (88.9%). The same bacterial family was assigned to 24 cases; the same genus, to 23 cases; and the same species, to 13 cases. In 22 of them, the etiological agent was represented by percentages > 99% of the reads and in two cases, by ~70%. Staphylococcus aureus was detected in a previously microbiological undiagnosed patient. Thus, microbiological diagnosis with 16S rRNA gene targeted-NGS was possible in one more sample than using traditional techniques. The remaining two patients showed no coincidence between traditional and 16S rRNA gene-targeted NGS microbiological diagnoses. In addition, 16S rRNA gene-targeted NGS allowed us to suggest coinfections that were supported by clinical data in one patient, and minority records also verified mixed infections in three cases. In our series, metataxonomics was valid for the identification of the causative agents, although more studies are needed before implementation of 16S rRNA gene-targeted NGS for the diagnosis of IE.

Clinical profile of children with parechovirus meningitis in Singapore

Human parechovirus (HPeV) is one of the most common causes of aseptic meningitis in children worldwide. This study aims to review the epidemiology, clinical presentation, and cerebrospinal fluid (CSF) findings in HPeV meningitis and compare these with Enterovirus (EV) meningitis. This is a retrospective study of children aged ≤ 1year admitted for HPeV meningitis between November 2015 and July 2017, with positive CSF HPeV PCR and negative blood and CSF bacterial cultures. The clinical findings were compared with a historical cohort of children with EV meningitis admitted between July 2008 and July 2011. There were 71 children with HPeV meningitis, aged between 2 and 127days, with the majority (96%) being ≤ 90days old. The most common symptoms reported were poor feeding (42%), tachycardia out of proportion to fever (27%), and lethargy (20%). Only 2 patients (3%) had CSF pleocytosis. Cerebral spinal fluid white blood cell counts ranged from 0 to 28 cells/mm3, with a median of 3 cells/mm3 [interquartile range (IQR) 1-6 cells/mm3]. When compared to our historical cohort of EV meningitis ≤ 90days old, children with HPeV meningitis ≤ 90days old were less likely to have CSF pleocytosis (OR 0.008, 95% CI 0.001-0.057). HPeV and EV meningitis are known to cause sepsis-like illness in infants < 90days old. This study further supports this, with the requirement for fluid bolus therapy for tachycardia or poor perfusion noted to be higher in children with HPeV meningitis ≤ 90days old (OR 6.3, 95% CI 2.7-14.2).

Bacterial DNA detection in very preterm infants assessed for risk of early onset sepsis

The aim of this study is to evaluate the diagnostic ability of multiplex real-time polymerase chain reaction (PCR) in very preterm infants assessed for risk of early onset neonatal sepsis (EOS). Prospective observational cohort study. Blood samples of preterm neonates≤32weeks of gestation were evaluated by commercial multiplex real-time PCR within 2h after delivery. The definition of EOS was based on positive blood culture and clinical signs of infection or negative blood culture, clinical signs of infection and abnormal neonatal blood count and serum biomarkers. Among 82 subjects analyzed in the study, 15 had clinical or confirmed EOS. PCR was positive in four of these infants (including the only one with a positive blood culture), as well as in 15 of the 67 infants without sepsis (sensitivity 27%, specificity 78%). Out of 19 PCR positive subjects, Escherichia coli was detected in 12 infants (63%). Statistically significant association was found between vaginal E.coli colonization of the mother and E.coli PCR positivity of the neonate (p=0.001). No relationship was found between neonatal E.coli swab results and assessment findings of bacterial DNA in neonatal blood stream. Multiplex real-time PCR had insufficient diagnostic capability for EOS in high risk very preterm infants. The study revealed no significant association between PCR results and the diagnosis of clinical EOS. Correlation between maternal vaginal swab results and positive PCR in the newborn needs further investigation to fully understand the role of bacterial DNA analysis in preterm infants.

9. The Skip Phenomenon in Staphylococcus aureus Bacteremia: Clinical Associations

BackgroundSerial blood cultures are integral in managing Staphylococcus aureus bacteremia (SAB) as clinicians rely on the results to determine infectious complication risks and antibiotic duration. Current IDSA guidelines suggest a single set of negative blood cultures is adequate evidence of SAB clearance. Several studies, however, have identified the skip phenomenon (SP), which is the occurrence of intermittent negative blood cultures, and have recommended obtaining additional blood cultures to document bacterial clearance (Table 1). We therefore examined patients who manifested the SP to determine its clinical significance and to study this, associations were tested for SP in relation to various baseline factors as well as clinical outcomes. MethodsWe performed a retrospective, multicenter study of all patients with a positive blood culture for S. aureus from January 2019 to December 2019 using data collected from electronic health records and the clinical microbiology laboratory. ResultsA total of 602 patients with SAB were identified and 495 patients were included in the investigation (Figure 1). Overall, 25 (5.1%) patients had the SP. Significant differences between those who did and did not manifest the SP included higher rates of injection drug use, automatic implantable cardioverter defibrillator, and community onset of infection in the SP cohort (Table 2). Moreover, the median duration of SAB was longer (3.2 [2.3-5.4] vs 1.90 [1.2-2.9] days, p=0.002), and high-grade SAB, (88.0% vs 58.7%, p=0.004), complicated bacteremia (92.0% vs 67.9%, p=0.011) and IE diagnosis (28.0% vs 11.3%, p=0.013) were all more common in the SP group. In unadjusted outcome analyses, association of SP with hospital length of stay was not significant, although a higher risk of in-hospital mortality among SP patients approached statistical significance (p=0.055). Analysis of 435 hospital survivors revealed no significant differences in rates of 1-year mortality or 90-day relapse between the two groups (Table 3). ConclusionFindings of the current investigation demonstrates an increased risk of SAB complications in patients with the SP and support the notion that serial negative blood cultures are needed to document clearance of SAB. Disclosures Larry M. Baddour, MD, Boston Scientific (Individual(s) Involved: Self): Consultant; Botanix Pharmaceuticals (Individual(s) Involved: Self): Consultant; Roivant Sciences (Individual(s) Involved: Self): Consultant Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant)

14. Effects of an Opt-Out Protocol for Antibiotic De-escalation among Selected Patients with Suspected Sepsis: The DETOURS Trial

BackgroundSepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. We conducted a randomized controlled trial (NCT03517007) of an opt-out protocol to decrease unnecessary antibiotics in selected patients with suspected sepsis.MethodsWe evaluated non-ICU adults remaining on broad-spectrum antibiotics with negative blood cultures at 48-96 hours at ten U.S. hospitals during September 2018-May 2020. A 23-item safety check excluded patients with ongoing signs of infection, concerning or inadequate microbiologic data, or high-risk conditions (Figure 1). Eligible patients were randomized to the opt-out protocol vs. usual care. The primary outcome was 30-day post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted by a pharmacist or physician to encourage antibiotic discontinuation or de-escalation using opt-out language, discuss rationale for continuing antibiotics, working diagnosis, and de-escalation and duration plans. Hurdle models separately compared the odds of antibiotic continuation and DOT distributions among those who continued antibiotics.Components of the De-Escalating Empiric Therapy: Opting-OUt of Rx in Selected patients with Suspected Sepsis (DETOURS) Trial Protocol ResultsAmong 9606 screened, 767 (8%) were enrolled (Figure 2). Common reasons for exclusion were antibiotics given prior to blood culture (35%), positive culture from non-blood sites (26%), and increased oxygen requirement (21%). Intervention patients had 32% lower odds of antibiotic continuation (79% vs. 84%, OR 0.68, 95% confidence interval [0.47, 0.98]). DOT distributions among those who continued antibiotics were similar (ratio of means 1.06 [0.88-1.26], Figure 3). Fewer intervention patients were exposed to extended-spectrum agents (38% vs. 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was not safe (31%). Safety outcomes such as mortality, readmission, sepsis relapse, C. difficile, and length of stay did not differ.DETOURS Trial Flow Diagram Flow of participants through the DETOURS Trial.Observed Days of Antibiotic Therapy Among Intervention and Control Subjects in the DETOURS Trial Post-enrollment days of antibiotic therapy among 767 DETOURS Trial participants in 10 US acute care hospitals within 30 days after enrollment. Dark pink color indicates percent overlap between intervention (purple) and control (light pink) groups.ConclusionIn this patient-level randomized trial of a stewardship intervention, the opt-out de-escalation protocol targeting selected patients with suspected sepsis resulted in more antibiotic discontinuations but did not affect safety events.Disclosures Rebekah W. Moehring, MD, MPH, UpToDate, Inc. (Other Financial or Material Support, Author Royalties) Michael Z. David, MD PhD, GSK (Board Member) Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)

1110. In Vivo Pharmacodynamics of Vancomycin Against Staphylococci in Young Infants

BackgroundCoagulase-negative staphylococci are the predominant pathogen causing late onset sepsis in young infants, however, the pharmacodynamic target for vancomycin therapy is unknown. This study aimed to determine the pharmacodynamic target of vancomycin in young infants with staphylococcal infections.MethodsRetrospective data were collected for infants aged 0-90 days with methicillin-resistant Staphylococcus aureus (MRSA or coagulase-negative staphylococci (CoNS) bacteraemia over a 4-year period at the Royal Children’s Hospital Melbourne, Australia. Vancomycin broth microdilution minimum inhibitory concentrations (MIC) were determined. A published pharmacokinetic model was externally validated using the study dataset and a time-to-event pharmacodynamic model developed using non-linear mixed effects modelling, with the event being the first negative blood culture. Simulations were performed to determine the 24-hour trough vancomycin concentration correlating with a 90% probability target attainment (PTA) of the area under the curve in the first 24-hours (AUC0-24) exceeding the identified target.ResultsThirty infants, 28 with CoNS and two with MRSA bacteraemia, who had 165 vancomycin concentrations determined were included. The vancomycin broth microdilution MIC was determined for 24 CoNS and one MRSA isolate, both with a median MIC of 1 mg/L (CoNS range 0.5 to 4). An AUC0-24 ≥3 00 mg/L·h was associated with a 7.8-fold increase in the chance of bacteriological cure for all staphylococci at any time point compared to an AUC0-24 < 300 mg/L·h (hazard ratio 95% CI: 3.21-18.8). The 24-hour trough concentrations associated with a 90% PTA of achieving this target were > 13-16 mg/L and > 8-12 mg/L for 6 and 12-hourly dosing, respectively. ConclusionOur study found that an AUC0-24 ≥ 300 mg/L·h was associated with a 7.8-fold increase in bacteriological cure in young infants with staphylococcal bloodstream infections. Disclosures All Authors: No reported disclosures

81. Reducing Unnecessary Blood Cultures Through Diagnostic Stewardship

BackgroundAt our institution, we learned the frequency of blood cultures was sometimes being changed from “Once” to “Daily” without a defined number of days. We hypothesized this led to unnecessary blood cultures being performed.MethodsOver a 3 month period from 12/6/2019-3/6/2020, we retrospectively evaluated the charts of patients who had a blood culture frequency changed to “Daily”. We evaluated if there was an initial positive blood culture within 48 hours of the “Daily” order being placed and the number of positive, negative, or “contaminant” sets of cultures drawn with the order. Contaminant blood cultures were defined as a contaminant species, present only once in the repeat cultures, and not present in initial positive cultures.Results95 unique orders were placed with 406 sets of cultures drawn from 89 adults. ~20% of the time (17 orders) the order was placed without an initial positive blood culture. This led to 62 sets of cultures being drawn, only 1 of which came back positive. 78/95 orders had an initial positive blood culture. The most common initial organisms were Staphylococcus aureus (SA) (38), Candida sp (10), Enterobacterales sp (10), and coagulase negative staphylococci (7). 43/78 (55%) orders with an initial positive set had positive repeat cultures. SA (26) and Candida sp (8) were most common to have positive repeats. Central line associated bloodstream infections (CLABSI) were found in 5 of the orders and contaminant species were found in 4 of the orders. 54% of the patients who had a “Daily” order placed did not have positive repeat cultures. The majority of the cultures were drawn from Surgical (40 orders) and Medical (35 orders) services. Assuming that SA and Candida sp require 48 hours of negative blood cultures to document clearance and other species require 24 hours, it was estimated that 51% of the cultures drawn using the "Daily" frequency were unnecessary. Cost savings over a year of removing the "Daily" frequency would be ~&14,000. Data from "Daily" blood culture orders drawn at Oregon Health & Science University from 12/6/2019-3/6/2020ConclusionUnnecessary blood cultures are drawn when the frequency of blood cultures is changed to "Daily". Repeat blood cultures had the greatest utility in bloodstream infections due to SA or Candida sp, and with CLABSI where the line is still in place. These results led to a stewardship intervention to change blood culture ordering at our institution.Disclosures All Authors: No reported disclosures

180. Duration of Therapy and Clinical Outcomes in Adult Oncology Patients with Uncomplicated Coagulase Negative Staphylococcal Bacteremia

BackgroundAlthough they are often considered contaminants, coagulase negative staphylococci (CoNS) can be pathogens especially in immunocompromised patients. National and local guidelines recommend treatment durations of 7 to 14 days, depending on specific clinical scenarios. The objective was to characterize the duration of treatment for CoNS bacteremia and clinical outcomes at our cancer center. MethodsWe conducted a retrospective chart review of adult patients ≥18 years old with ≥1 blood culture with growth of CoNS between 1/1/17 and 12/31/19 at our cancer center. Patients with complicated CoNS bacteremia and polymicrobial infections were excluded.ResultsAmong 128 patients identified during the study period, 98 met inclusion criteria (Figure 1). Most patients (N= 92; 94%) had a hematologic malignancy as the underlying oncologic diagnosis, and 68 (69%) were hematopoietic stem cell transplant recipients. The median total antibiotic duration was 13 days, and median duration from the date of 1st negative blood culture was 12 days; 29 (30%) patients were treated for a total duration of >14 days (Figure 2). The catheter was retained in 67 (68%) and exchanged in 4 (4%) of the cases. Three (3%) patients had recurrence of bacteremia within 30 days of treatment completion, and 8 (8%) patients were transferred to the ICU within 7 days of the index blood culture. The 30-day crude mortality rate was 10%. The most commonly used antibiotic for treatment was vancomycin (N= 95; 97%), and 32 (34%) patients on vancomycin had an increase in serum creatinine of ≥ 50% from baseline. Five (5%) patients discontinued vancomycin due to nephrotoxicity, and 4 (4%) patients required hemodialysis.Figure 1. Results Overview Among 128 patients identified during the study period, 98 met inclusion criteria. Of those included, 36 had one set of blood cultures that were positive for CoNS and 62 patients had at least two sets of blood cultures that were positive for CoNS.Figure 2. Duration of Antibiotic Treatment We evaluated duration of treatment based on total antibiotic duration and duration from date of 1st negative blood culture. The number of patients is noted above each bar.ConclusionAlthough the majority of patients were treated for ≤14 days for uncomplicated CoNS bacteremia, nearly 1/3 of patients were treated for > 14 days. Recurrent bacteremia was uncommon despite catheter retention in most patients. Relatively high rates of vancomycin associated nephrotoxicity highlight opportunities for antimicrobial stewardship to limit duration of vancomycin therapy among cancer patients with uncomplicated CoNS bacteremia. Disclosures All Authors: No reported disclosures

Candidemia: Evolution of Drug Resistance and Novel Therapeutic Approaches.

Candidemia and invasive candidiasis are the most common healthcare-associated invasive fungal infections, with a crude mortality rate of 25–50%. Candida albicans remains the most frequent etiology, followed by C. glabrata, C. parapsilosis and C. tropicalis. With the exception of a limited number of species (ie: C. krusei, C. glabrata and rare Candida species), resistance to fluconazole and other triazoles are quite uncommon. However, recently fluconazole-resistant C. parapsilosis, echinocandin-resistant C. glabrata and the multidrug resistant C. auris have emerged. Resistance to amphotericin B is even more rare due to the reduced fitness of resistant isolates. The mechanisms of antifungal resistance in Candida (altered drug-target interactions, reduced cellular drug concentrations, and physical barriers associated with biofilms) are analyzed. The choice of the antifungal therapy for candidemia must take into account several factors such as type of patient, presence of devices, severity of illness, recent exposure to antifungals, local epidemiology, organs involvement, and Candida species. The first-line therapy in non-neutropenic critical patient is an echinocandin switching to fluconazole in clinically stable patients with negative blood cultures and azole susceptible isolate. Similarly, an echinocandin is the drug of choice also in neutropenic patients. The treatment duration is 14 days after the first negative blood culture or longer in cases of organ involvement. An early removal of vascular catheter improves the outcome. The promising results of new antifungal molecules, such as the terpenoid derivative ibrexafungerp, the novel echinocandin with an enhanced half-life rezafungin, oteseconazole and fosmanogepix, representative of new classes of antifungals, are discussed.

Fever and Abdominal Pain in a 10-year-old with Autism.

Fever and Abdominal Pain in a 10-year-old with Autism.

High Mortality among Premature Neonates with Positive Blood Culture Neonatal Sepsis in a Tertiary Hospital, Tanzania: A Call for Action.

Well-documented vital signs are key in the prediction of sepsis in low- and middle-income countries. We determined prevalence, associated factors, and outcomes of positive blood culture sepsis in premature neonates at Bugando Medical Centre Mwanza, Tanzania. Temperature, oxygen saturation, heart rate, respiratory rate, and random blood glucose were repeatedly recorded at admission, 8 h, and 24 h in all 250 neonates enrolled. Clinical and microbiological data were collected from patient records followed by descriptive data analysis. The mean age of the neonates was 3 ± 5.2 days, with the majority (90%) aged <10 days. The prevalence of positive blood culture sepsis was 21.2% (95% CI: 16.1–26.2). The fluctuation of the random blood glucose (RBG) (aOR = 1.34, 95% CI: (1.07–1.67), p = 0.010), low oxygen saturation (aOR = 0.94, 95% CI: (0.88–0.99), p = 0.031), premature rupture of membrane aOR = 4.28, 95% CI: (1.71–10.71), p = 0.002), gestational age < 34 weeks (aOR = 2.73, 95% CI: (1.20–6.24), p = 0.017), and home delivery (aOR = 3.90, 95% CI: (1.07–14.19), p = 0.039) independently predicted positive blood culture. Significantly more deaths were recorded in neonates with a positive blood culture than those with a negative blood culture (32.1% vs. 5.1%, p < 0.001). In limited-resource settings, clinicians should use the vital signs and clinical information to initiate timely sepsis treatment among preterm neonates to prevent deaths and other morbidities.

P061 Kawasaki disease: a case series from a tertiary Hospital in Kenya

Abstract Background Kawasaki disease (kDa) is a childhood vasculitides that affects small and medium-sized arteries. It is self-limiting but when left untreated can cause coronary artery aneurysms in about 25% of children1. The diagnosis is clinical and is made with the criteria of fever for at least five days, and at least four out of five other clinical signs: bilateral non-exudative conjunctivitis, oral mucous membrane changes, peripheral extremity changes, polymorphous rash, and cervical lymphadenopathy. Incomplete kDa is diagnosed with fever for at least five days and at least 2–3 of the principal signs, with suggestive lab investigations and lack of an alternative diagnosis1. kDa is named after Dr Tomisaku Kawasaki who first described it in 1967 in Japan2. The highest incidence of kDa continues to be reported among Asian children, with an incidence rate of 264.8 per 100 000 population aged 0–4 years as per Japan’s latest nationwide survey3. In Africa, the true incidence is unknown but several case reports have been published. A 2016 paper by Gorrab et al.4 found that the annualized incidence rate of kDa in the Maghreb children living in Quebec (18.49/year/100 000 children under 5 years of age) was 4–12 times higher than reported in their countries of origin- Tunisia, Morocco, and Algeria (0.95, 4.52, and 3.15, respectively) suggesting a likelihood of under-diagnosis. This case series sought to highlight the characteristics, presentation, and management of patients diagnosed with kDa in a tertiary hospital in Kenya. Methods This was a retrospective cross-sectional study carried out by reviewing the charts of all the patients with a discharge diagnosis of kDa from January 2013 to December 2017 at the Aga Khan University Hospital, Nairobi. Their demographics, presentation, diagnostic work-up, and management are reported. Analysis was done by descriptive statistics using the Microsoft Excel 2016 Application. Results A total of 15 cases were identified and the patient characteristics and presentation are as tabulated below: In addition to elevated inflammatory markers (C reactive protein and/or Erythrocyte Sedimentation Rate), a significant number of the patients also had sterile pyuria (9/9), hypoalbuminemia (8/10), thrombocytosis (8/15), and anaemia (11/15). Nine out of eleven had negative blood cultures. Fourteen out of the fifteen patients had echocardiograms done during admission. Only one patient was found to have abnormal findings of bilaterally dilated coronaries arteries. Five patients had at least one documented repeat echocardiogram. Fourteen patients received Intravenous Immunoglobulin (IVIG), with 13 of them responding to treatment. No adverse effects were reported after treatment. One patient did not improve and needed a second dose of IVIG and intravenous methylprednisone (30 mg/kg). Fourteen patients received aspirin but dosing varied from high (80–90 mg/kg/day) to moderate (30–50 mg/kg/day) to low dose (3 mg/kg/day). One patient on high-dose aspirin was noted to have developed symptoms consistent with aspirin-induced bronchospasm and was changed to low dose. Conclusion This case series highlights the presence of kDa in the Kenyan pediatric population with patient characteristics similar to what is reported globally. Diagnosis was made after a mean of about 7 days, possibly due to low awareness of the disease among healthcare professionals. Management with IVIG in most cases was successful but more guidance is needed around the use of steroids and the dosing of aspirin.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Associated with Enoxaparin Therapy in a Pediatric Patient

Introduction: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare drug hypersensitivity reaction characterized by diffuse skin eruption with systemic symptoms (fever, lymphadenopathy, elevated transaminases, leukocytosis with eosinophilia and atypical lymphocytes) which develops 2-6 weeks after exposure to inciting medications. Clinical presentation is variable and nonspecific. DRESS syndrome is more common in adults, can be life threatening, and is most commonly seen with antibiotics, antiepileptic drugs, and allopurinol. An inciting drug is identified in the majority of cases. DRESS syndrome has been described rarely in association with Vitamin K antagonists and direct oral anticoagulants. In an in-depth examination of existing literature, there are only two reported cases of DRESS syndrome associated with enoxaparin therapy, both in adult patients and no reports of pediatric DRESS syndrome secondary to anticoagulants. We present a case of a pediatric patient with DRESS syndrome associated with enoxaparin therapy.Case Report: A previously healthy 11-year-old female was admitted with sepsis secondary to osteomyelitis and periosteal abscess of the left lower extremity, as well as MRSA bacteremia. The patient was initiated on clindamycin and vancomycin for treatment of underlying infections. A left lower extremity ultrasound with doppler was obtained due to lower extremity swelling and demonstrated an acute deep venous thrombus of the left popliteal vein. She was initiated on a heparin drip and subsequently transitioned to enoxaparin one week later. Several weeks into her hospital course (two weeks after initiation of enoxaparin), she developed facial swelling, a generalized morbilliform rash, and diffuse lymphadenopathy both on exam and abdominal imaging. She continued to have persistent fevers despite multiple washouts of the extremity, appropriate antimicrobial coverage, and negative blood cultures. Liver enzymes concurrently increased (AST 362 IU/L (normal 5-60 IU/L), ALT 371IU/L (normal <35 IU/L) at peak) with development of clinical symptoms. Eosinophilia was not present on initial CBC, though she subsequently developed mild eosinophilia (1.1 K/ul at peak). HHV6, CMV, and EBV serologies were all negative. Skin biopsy was performed and was consistent with a drug eruption. Using the RegiSCAR criteria for DRESS syndrome, this constellation of labs and symptoms indicate a definite case of DRESS syndrome with a score of 6 (final score >5 is needed for a definite case). The patient was started on treatment with high-dose steroids. Clindamycin and vancomycin were both discontinued due to their known association with DRESS syndrome. She was transitioned to doxycycline, however, no improvement in rash, fevers, or liver enzymes was seen over the course of five days. Given this, enoxaparin was transitioned to apixaban. The patient improved with resolution of rash, fevers, and improvement of liver enzymes and eosinophilia within a few days of the discontinuation of enoxaparin.Conclusion: The diagnosis of DRESS syndrome can be challenging due to its nonspecific presentation, particularly in pediatric patients where symptoms can overlap with common viral syndromes and Kawasaki disease, and therefore requires a high index of suspicion. Though children with DRESS syndrome have a better prognosis than adults, prompt recognition and treatment is required to limit morbidity and mortality. In pediatric patients receiving treatment with enoxaparin, DRESS syndrome should be included on the differential for those who develop persistent fevers, lymphadenopathy, rash, transaminitis and/or eosinophilia, and discontinuation of enoxaparin should be considered. DisclosuresWeyand: Takeda: Consultancy; Genentech: Consultancy; Novo Nordisk: Research Funding; Sanofi: Consultancy, Research Funding.

O11 Neisseria Meningitidis as a cause of isolated bilateral polyarticular native knee joint septic arthritis

O11 <i>Neisseria Meningitidis</i> as a cause of isolated bilateral polyarticular native knee joint septic arthritis

Comparison of Clinical Characteristics and Outcomes Between Positive and Negative Blood Culture Septic Patients: A Retrospective Cohort Study.

BackgroundFew studies have studied the relationship between blood culture and mortality in sepsis patients. The aim of this study was to compare the characteristics and outcomes of positive and negative blood culture sepsis.MethodsWe performed a study on 640 patients suffering from sepsis in Beijing Chao-Yang Hospital from October 2017 to December 2019. The primary findings revolved around length and expenditure of hospital stay, the possibility of suffering from acute respiratory distress syndrome (ARDS), and any requirements for mechanical ventilation. The secondary findings revolved around whether the patient died early (28-day) or late (28-to-90-day).ResultsA total of 592 of the 640 patients met the inclusion criteria for sepsis, with 274 of them having culture-positive results. The culture-positive patients were mostly elderly suffering from diabetes and at risk of cancer, with a higher white blood cell count, and higher procalcitonin. Additionally, they scored higher in their acute physiology and chronic health evaluation II score (15 vs.11, P=0.010), as well as in their predisposition, infection, response, and organ dysfunction (17 vs 11, P<0.001) than the individuals in the culture-negative group. Culture-positive patients had a longer duration of hospital stay (14 vs 6, P<0.001) and higher in-hospital mortality (14.6% vs 8.5%, P=0.019) than culture-negative ones. No significant difference in intensive care unit (ICU) mortality (45.7% vs.36.4%, P=0.254) or early mortality (9.5% vs 7.2%, P=0.321) was noted between the two groups. However, the culture-positive patients had increased late mortality (15.7% vs.6.9%, P=0.001), when compared with those with culture-negative results in the cohort. Furthermore, the culture-positive patients who received the appropriate antibiotics early had a lower mortality rate than the culture-negative patients (7.3% vs.14.2%, P=0.008).ConclusionCulture-positive patients had higher in-hospital mortality, comparable early mortality, and worse late mortality than the culture-negative patients. Early appropriate use of antibiotics might reduce mortality and improve clinical prognosis.