A discrepant presentation of bacteremia in the emergency department linked to a Fusobacterium nucleatum infection: a case report

Background Fusobacterium nucleatum is an anaerobic bacterium mainly responsible for acute or chronic infection of the ear, nose, and throat, potentially bacteremic with a risk of extraoral metastatic infection. Bacteremia occurs mainly in the elderly or in immunodeficient individuals, with high mortality. F. nucleatum is not the first cause of tonsillar infection in emergency departments, which are more often the consequence of a viral or streptococcal infection, but it is a risk factor for severe bacterial infection, especially in a viral pandemic context. Case presentation A 25-year-old European woman with no history presented to the emergency department with fever (38.9 °C), pharyngeal symptoms, intermittent headaches, and alteration of general condition. On examination, she presented odynophagia associated with moderate tonsillar hypertrophy, her neck was painful but flexible. A rapid diagnostic test for beta-hemolytic group streptococcus was negative. First biological analyses revealed an inflammatory syndrome with C-reactive protein of 76 mg/L. Procalcitonin was measured secondarily, and was 2.16 µg/L. Faced with discordant clinical and biological findings, a lumbar puncture was performed, which came back negative. At hour eight, hypotension was observed but corrected after filling with physiological serum. The patient was hospitalized for monitoring, based on a hypothesis of severe viral presentation. At hour 24, pyrexia confirmed this hypothesis. A spontaneous but transient improvement and no new hemodynamic event led to early discharge. At day three, she was rehospitalized for increased and continuous headaches, without hemodynamic severity. A broad-spectrum probabilistic antibiotic therapy of ceftriaxone and metronidazole was started due to first blood cultures positive for anaerobic Gram-negative bacilli, while waiting for identification of the pathogen. Three days later, F. nucleatum was identified. According to the microbiological results, antibiotic therapy was adapted with amoxicillin and clavulanic acid, and no further complications were observed during clinical or complementary examinations. The final diagnosis was a F. nucleatum oropharyngeal infection complicated by bacteremia, without metastatic spread. Conclusion The etiologies of tonsillar infection are not limited to benign viruses or bacteria. These should not be overlooked in emergency medicine, especially when the clinical presentation is discrepant. A combination of early bacterial investigations as blood culture and close clinical monitoring is the only safe way to detect bacteremia, especially in immunocompetent patients.

1373. Racial Disparities in Clinical Characteristics and Outcomes for Methicillin Susceptible and Methicillin-Resistant Staphylococcus aureus Bacteremia

Background Bacterial bloodstream infections (BSI) are one of the most described syndromes in infectious diseases, but the presence of racial disparities in BSI is unclear. The purpose of this project was to determine if racial disparities exist in patients with S. aureus bacteremia (SAB). Methods Data was used from a prospective cohort of patients with SAB at Duke University Medical Center from 1995-2015. Patients were categorized as African American (AA) or White. Characteristics of interest included discharge disposition, metastatic infection, persistence of SAB, and in-hospital mortality stratified by methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) infections. Statistical comparisons were performed for binary variables with Fisher’s Exact test and continuous variables with Kruskal-Wallis test. Results Among the 2396 patients with SAB, 1496 (62.4%) were White and 900 (37.6%) were AA. 1241 patients (51.8%) had MSSA bacteremia overall. Whites comprised 63.6% of MSSA and 61.2% of MRSA infections. AA were younger (MSSA [median, IQR]: 53.0, 44.0-64.0 vs. 62.0, 50.0-71.0, p< 0.0001; MRSA: 58.0, 46.5-69.5 vs. 64.0, 52.0-74.0, p< 0.0001) and more likely to be female (MSSA: 46.2% vs 38.2%, p= 0.007; MRSA: 53.1% vs 41.9%, p< 0.001). AA had higher rates of diabetes, hemodialysis, HIV infection for both MSSA and MRSA, but higher rates of injection drug use for MSSA only; Whites had higher rates of neoplasm, corticosteroid use, surgery for MSSA and MRSA, but higher rates of transplant for MRSA only (Figures 1, 2). AA had higher Acute Physiology Scores (MSSA: 9.0 vs 6.0, p< 0.001; MRSA: 8.0 vs 7.0, p=0.005). AA experienced increased rates of healthcare-associated infection (MSSA: 69.9% vs. 58.3%, p=0.0002; MRSA: 68.1% vs. 50.6%, p< 0.0001). Although Whites were more likely to have in-hospital mortality for MRSA (24.6 vs. 19.2, p=0.0359), discharge disposition, metastatic infection, and persistence did not vary significantly by race. Conclusion Racial disparities exist in SAB, more so for patient characteristics than for outcomes. AA patients were younger, had a different set of comorbidities, and had more acute presentations. Although Whites had higher rates of in-hospital mortality, all other outcomes were similar. Disclosures Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant)

657. Genomic Insights into Virulence Factors Affecting a Tissue-invasive Klebsiella pneumoniae Infection

Background Japan is one of the hypervirulent Klebsiella pneumoniae (hvKp) endemic areas, resulting in an alarming issue in actual clinical settings. However, little is known regarding key virulence factors responsible for hvKp infection. Methods We analyzed K. pneumoniae isolates collected between 2017 and 2019, and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infection or uncomplicated bacteremia. Isolates belonging to the K. pneumoniae species complex were excluded. Results We analyzed 112 isolates, including 19 hvKp, 67 cKp, and 26 colonizers, by whole-genome sequencing. Population genomics revealed that the K1-sequence type (ST) 82 clade was distinct from that of K1-ST23 clone (Figure 1). The virulence-gene profiles also differed between K1-ST82 (aerobactin and rmpA) and K1-ST23 (aerobactin, yersiniabactin, salmochelin, colibactin, and rmpA/rmpA2). The K2 genotype was more diverse than that of K1. A neighboring subclade of K1-ST23 (comprising ST29, ST412, ST36, and ST268) showed multidrug-resistance and hypervirulence potentials. Logistic-regression analysis revealed that diabetes mellitus was associated with K. pneumoniae infection (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.14–14.8). No significant association was found between hvKp diagnosis and clinical characteristics, such as diabetes mellitus or community acquisition (Table 1). The K1 genotype (OR: 9.02; 95% CI: 2.49–32.7; positive-likelihood ratio [LR]: 4.08), rmpA (OR: 8.26; 95% CI: 1.77–38.5; positive LR: 5.83), and aerobactin (OR: 4.59; 95% CI: 1.22–17.2; positive LR: 3.49) were substantial diagnostic predictors of hvKp (Table 2). Figure 1. Phylogenetic distribution of genetic virulence factors in 112 K. pneumoniae isolates The highlighted strains are clinically pathogenic (orange, hypervirulent K. pneumoniae; yellow, classical K. pneumoniae; sky blue, colonization). The non-highlighted strain (NTUH-K2044) is a reference K. pneumoniae strain. Conclusion In hvKp-rich settings, diabetes mellitus, community-acquisition, and siderophores other than aerobactin were not remarkable predictors of hvKp infection. However, the K1 genotype, rmpA, and aerobactin were found to be substantial predictors, warranting clinical assessment of any possible/further pyogenic (metastatic) infection. We believe that these findings shed light on key hvKp virulence factors. Disclosures All Authors: No reported disclosures

An Outbreak of Strangles in Arabian Horses in Saudi Arabia: Epidemiology, Clinical Signs and Treatment Outcomes

This study was carried out to investigate an outbreak of strangles in horses at the Qassim Region, Central Saudi Arabia. From 29 horses included in this study, the disease was observed in 13, five of them were died: representing a morbidity rate of 44.8% and a mortality rate of 17.24%. The morbidity and mortality rates significantly (P≤0.05) differed among different age groups. In contrast, the case fatality rate was not significantly different among different ages. Gender has no significant effect on disease occurrence. Clinically, signs observed in infected horses were high fever, anorexia, soft non-productive cough, muco-purulent bilateral nasal discharge, enlargement and abscessation of submandibular lymph nodes. Metastatic infection, including abdominal abscessation, was observed in 5 of the infected cases where signs of acute abdominal pain were recorded. Streptococcus equi subspecies equi was the only organism isolated from the lesions. Significant increases in the total white blood cells and neutrophils were detected in the diseased horses compared to healthy ones. Penicillin therapy, surgical intervention of the ripened sub-mandibular abscesses, isolation of healthy horses away from infected ones and thorough disinfection of the contaminated environment were the control measures that were applied to manage this outbreak. Treatment was very effective in the typical form of the disease whereas it had no value in the bastard form. Finally, it can be concluded that strangles in horses in the Qassim Region represents a great risk due to the high case fatality rate, and therefore using a protective vaccine is essential.

Endogenous Endophthalmitis and Liver Abscess: A Metastatic Infection or a Coincidence?

<i>Klebsiella pneumoniae</i> is a gram-negative pathogen that is a common cause of severe infections, including pyogenic liver abscess. Dissemination of <i>K. pneumoniae</i> to other organs, including the eye, is associated with significant morbidity and mortality. In the particular case of endogenous endophthalmitis (EE) by <i>K. pneumoniae</i> the prognosis is poor. We report the case of a middle-aged female with <i>K. pneumoniae</i> liver abscess. The patient developed metastatic endophthalmitis that was aggressively treated with systemic antibiotics. The liver abscess resolved with antimicrobials and percutaneous transhepatic drainage, but regarding the endophthalmitis she was discharged from our hospital without recovery of her eyesight. Metastatic spread to the eye should be considered in all patients with liver abscesses who experience ocular signs and symptoms in order to establish a timely diagnosis of EE.

Methicillin-Resistant Staphylococcus aureus Peritonitis due to Hematogenous Dissemination from Central Venous Catheter in a Maintenance Dialysis Patient

<i>Staphylococcus aureus</i> is a Gram-positive bacterium commonly associated with severe infections in hospitalized patients. <i>S. aureus</i> produces many virulence factors leading to local and distant pathological processes. Invasiveness of <i>S. aureus</i> generally induces metastatic infections such as bacteremia, infective endocarditis, osteomyelitis, arthritis, and endophthalmitis. Peritoneal localization from extra-abdominal infection can be a potential consequence of <i>S. aureus</i> infection. Two cases of metastatic peritonitis have been described in patients on peritoneal dialysis with concomitant peripheral vascular catheter-related bloodstream infection. We reported a case of peritoneal metastatic infection caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) in a patient on maintenance hemodialysis. A 37-year-old man was admitted with fever and chill due to jugular central vascular catheter (CVC)-related bloodstream infection caused by MRSA<i>.</i> CVC was placed after switching the patient from peritoneal dialysis to hemodialysis for scarce adherence to fluid restriction. Detection of MRSA on the peritoneal effluent combined with a total white blood cell count of 554 cells/mm³ prompted the diagnosis of satellite MRSA peritonitis. Antibiotic treatment with daptomycin and simultaneous CVC and peritoneal catheter removal resolved the infectious process. No further metastatic localizations were detected elsewhere. In conclusion, <i>S. aureus</i> can induce metastatic infections far from the site of primary infection. As reported in this case, peritonitis can be secondary to the hematogenous dissemination of <i>S. aureus</i> especially in hospitalized patients having a central line.

Independent prediction of aspartate aminotransferase to alanine aminotransferase ratio for adverse outcomes of patients with pyogenic liver abscess

Background: In viral hepatitis, an increase in the ratio of aspartate aminotransferase to alanine aminotransferase (AAR) is associated with poor prognosis. However, the relationship between AAR and pyogenic liver abscess (PLA) remains to be unclear. In this study, the relationship between AAR and adverse outcomes in PLA patients were explored, and the predictive value of AAR were evaluated. Methods: In total, 240 PLA patients were consecutively enrolled in this study and followed up at 3 months. Univariate analysis, receiver-operating characteristic (ROC) curve analysis and multivariate logistic regression analyses were performed. Results: According to the ROC curve of AAR for adverse outcomes, the patients were divided into two groups using a cutoff of 0.97. Patients with high AAR had higher risk of mortality rate (16.5% vs 2.9%), empyema (23.7% vs 10.4%), metastatic infection (19.1% vs 9.7%), acute myocardial (7.3% vs 0.7%), acute hepatic failure (7.3% vs 2.2%) and septic shock (13.7% vs 4.4%) than patients with low AAR (all P<0.05). after adjusting for potential confounding factors in our logistic model, high AAR was independently associated with death (odds ratio (OR)=6.17, 95% of confidence interval (CI)=1.88-20.26) and all adverse outcomes (OR=4.03, 95% CI=2.12-7.66). AAR had the largest area under ROC curve (AUC) than ALT, AST in all adverse outcomes (AUC=0.690, cutoff value=0.97, P<0.01) and death prediction (AUC=0.821, cutoff value=1.31, P<0.01). Conclusion: In the clinical application of PLA, AAR may be a good method to predict the prognosis.

Microbial Cell-Free DNA Identifies Etiology of Bloodstream Infections, Persists Longer Than Conventional Blood Cultures, and its Duration of Detection is Associated with Metastatic Infection in Patients with Staphylococcus aureus and Gram-Negative Bacteremia

Background Microbial cell-free DNA (mcfDNA) sequencing of plasma can identify presence of a pathogen in a host. This study evaluated the duration of pathogen detection by mcfDNA sequencing vs. conventional blood culture in patients with bacteremia. Methods Blood samples from patients with culture-confirmed bloodstream infection were collected within 24 hours of the index positive blood culture and 48 to 72 hours thereafter. mcfDNA was extracted from plasma and next-generation sequencing (NGS) applied. Reads were aligned against a curated pathogen database. Statistical significance was defined with Bonferroni adjustment for multiple comparisons (p &lt; 0.0033). Results A total of 175 patients with Staphylococcus aureus bacteremia (SAB; n=66), Gram-negative bacteremia (GNB; n=74), or non-infected controls (n=35) were enrolled. The overall sensitivity of mcfDNA sequencing compared to index blood culture was 89.3% (125/140) and the specificity was 74.3%. Among patients with bacteremia, pathogen specific mcfDNA remained detectable for significantly longer than conventional blood cultures (median 15 days vs. 2 days; p&lt;0.0001). Each additional day of mcfDNA detection significantly increased the odds of metastatic infection (Odds Ratio [OR]: 2.89; 95% Confidence Interval [CI]: 1.53-5.46; p=0.0011). Conclusions Pathogen mcfDNA identified the bacterial etiology of bloodstream infection for a significantly longer interval than conventional cultures, and its duration of detection was associated with increased risk for metastatic infection. mcfDNA could play a role in the diagnosis of partially treated endovascular infections.

Infección metastásica por Staphylococcus aureus en neonatos: a propósito de un caso

Metastatic infection as an infrequent complication of Staphylococcus aureus bacteremia in neonates is challenging due to the limited literature. To report the clinical case of a premature neonate who developed a metastatic infection as a complication of S. aureus bacteremia. We present the case of a premature neonate admitted to the Neonatal Intensive Care Unit, diagnosed with bacterial sepsis, neonatal respiratory distress syndrome, and involvement by premature rupture of the membrane. A patch catheter was inserted, and he was successfully treated for E. coli bacteremia. He was re-admitted for late sepsis due to infection with multi-sensitive S. aureus in a patch catheter. An abscess appears on the front of the chest due to S. aureus, confirming metastatic infection. The abscess was drained with a favorable resolution of the clinical picture. In neonates submitted to invasive procedures, it is essential to monitor the clinical evolution and early identification of metastatic infection after Staphylococcus aureus bacteremia and provide early treatment to avoid sequelae.

Changing characteristics of S. aureus bacteremia caused by PVL-negative, MRSA strain over 11 years

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of infection. We conducted a longitudinal study to evaluate changes in clinical and microbiological characteristics as well as outcomes of sequence type (ST) 72 MRSA bacteremia. We reviewed adult patients enrolled in a prospective cohort with ST72 MRSA bacteremia from August 2008 to December 2018 at Asan Medical Center, Seoul, South Korea. Changes in clinical characteristics, outcomes, and microbiological characteristics of patients over time were evaluated. Generalized linear and linear regression models were used to evaluate changes. Of the 1,760 isolates, 915 (62%) were MRSA bacteremia and 292 (31.9%) were ST72 MRSA. During the study period, the relative risk (RR) of MRSA bacteremia decreased annually by 3.7%; however, among MRSA bacteremia, RR of ST72 MRSA increased annually by 8.5%. Vancomycin minimum inhibitory concentration (MIC) decreased over the study period. Metastatic infection, persistent bacteremia, and recurrence of bacteremia within 12 weeks decreased significantly. There were no significant changes in 30-d and 12-week mortality. Antibiotic susceptibility of ST72 MRSA was evaluated, and the resistance rate to erythromycin decreased significantly. ST72 MRSA incidence increased annually; its vancomycin MIC and erythromycin resistance rate decreased over the 11 years.