Saleh, Omar Abu

Abstract Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.

Abstract Background Although trimethoprim-sulfamethoxazole (TMP-SMX) has consistently demonstrated significant interindividual variability, therapeutic drug monitoring is used to optimize dosing and avoid adverse reactions that may contribute to treatment interruption. While data exists on the use of SMX level monitoring in pneumocystis, there is a lack of data in SMX serum monitoring utility for invasive Nocardia infections. Methods We retrospectively reviewed adults who received TMP-SMX to treat nocardial brain abscess (BA) and underwent SMX testing level from January 2010 to December 2020. Results Overall, 24 patients had Nocardia spp. BA; Twenty-two (91.7%) were treated with TMP-SMX, and 16/22 (72.7%) had a documented SMX serum level. The median age was 64 (IQR 58-69) years, and the majority were males (77.3%). Compared to those who did not have a documented SMX serum level, patients with SMX levels had a higher prevalence of hemodialysis (HD, 42.9% vs. 33%; P=.99) and malignancy (50% vs. 33.3%; P=.65). The most common BA location was the frontal lobe (43.8% vs. 33.3%; P=.99), with a single (68.8% vs. 50%; P=.62) and smaller (1.3 vs. 1.9 cm; P=.58) brain fluid collection, and with fewer midline shift (6.3% vs. 16.7%; P=.48), respectively. The median TMP-SMX duration was 350 days (P=.31). The most common dosing was 2-double strength, three times a day (31.8%). The SMX median level was 158.5 (IQR 120-218) mcg/mL, collected at two hours (75%) post-administration in the induction phase (81.3%). The most common recommendation was to continue therapy based on the level results. Eleven (46%) patients had a level >150 mcg/mL, and 5 (45.5%) reported drug toxicity, including nausea in 3, acute kidney injury in 2, and thrombocytopenia in 2 patients. Ninety-four percent of the patients with SMX levels had surgical intervention for therapeutic purposes vs. 83% of those without it (P=.65). A total of 11 (50%) patients were cured, 3 (18.8%) relapsed, and 2 (12.5%) died. Conclusion Patients with SMX serum level monitoring are more likely to be on HD, during the induction phase and among those with higher and more frequent dosing. About half of patients with SMX levels >150 mcg/mL experienced drug toxicity; however, SMX levels did not impact patient outcome and length of treatment. Disclosures All Authors: No reported disclosures

Abstract Background Staphylococcus aureus bacteremia (SAB) is common and is characterized by high rates of morbidity and mortality. The clinical importance of a single positive blood culture bottle (SPBCB), however, is poorly defined despite it being a frequent laboratory finding. We therefore examined patients with SPBCB to determine its clinical significance and to understand the rationale of current practice. Methods We performed a retrospective, multicenter study of patients with a SPBCB for S. aureus in initial cultures from January 2019 to December 2019 using data collected from both electronic health records and the clinical microbiology laboratory. Results Overall, 534 patients with SAB were identified, and 118 (22.1%) had a SPBCB. Among SPBCB cases, 106 (89.3%) were classified as clinically significant while 12 were considered contaminated or of unclear clinical significance. Baseline characteristics were similar between the groups (Table 1). A majority (92.4%) received antibiotic therapy, but patients with clinically significant bacteremia were treated with a longer antibiotic course (25.9 vs 5.7 days, p< 0.001). Outcomes between those with SPBCB (contaminant vs clinically significant) were similar (Table 2). Of note, while there was no difference in use of echocardiography based on PREDICT criteria between the clinically significant SPBCB vs. the multiple positive blood culture bottles (MPBC) cohorts (Table 3), significant differences were seen in both frequency of echocardiography (65.1% vs. 84.6%, P< 0.001) and IE diagnosis (3.8% vs. 14.2%, P=0.002) for patients in the SPBCB vs. MPBC groups, respectively. In addition, those with MPBC had higher 90-day, 6-month and 1-year mortality rates. Conclusion SPBCB was documented in almost one-quarter of SAB cases and should trigger a thorough investigation as its associated mortality was high and complications, including IE, occurred. Although some SPBCB cases may represent contamination, antibiotic treatment of SPBCB was commonplace. Patients with clinically significant SPBCB were less likely to undergo echocardiography and had a reduced prevalence of an IE diagnosis as compared to those with MPBC. Patients with SPBCB may have a more favorable long-term prognosis as compared to that in patients with MPBC. Disclosures Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant) 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

Abstract Background Despite safety communications from the Food and Drug Administration (FDA) regarding the outbreak of Mycobacterium chimaera infections (MCIs) from contaminated heater-cooler devices, new cases continue to be identified. Methods We retrospectively reviewed confirmed cases of MCI that were managed at Mayo Clinic sites (Arizona, Florida, and Minnesota) from 09/2015 to 01/2021. Clinical histories including prior cardiovascular surgery were recorded. Diagnostic workup including ophthalmologic examination, imaging, and laboratory testing was reviewed. Treatment and survival outcomes on follow-up were obtained. Results Twelve patients with MCI were included. All patients had aortic valve or graft replacement. Five patients had their surgical procedures following the 10/15/2015 FDA safety communication. The mean time from surgery to symptom onset (range) was 32 (13–73) months. Ten of 11 patients who underwent ophthalmologic examination had chorioretinal abnormalities. Three patients who underwent microbial cell-free deoxyribonucleic acid sequencing tested positive for M. chimaera, which was subsequently confirmed with blood culture growth. Echocardiography and positron emission tomography/computed tomography (PET/CT) revealed evidence of prosthetic valve/graft infection in 7/12 (58.3%) and 6/10 (60.0%) of cases, respectively. Seven patients (58.3%) underwent redo cardiovascular surgery. Of these, 1 patient died 2 days postdischarge, 1 experienced spinal osteomyelitis relapse, and another had interval prosthetic valve fluorodeoxyglucose (FDG) uptake on PET/CT suspicious for recurrent infection. Among 4 patients on medical therapy only, 3 expired or transitioned to hospice during follow-up. Conclusions MCI continues to occur despite the FDA communications. Incorporation of ophthalmologic examination and use of advanced tools may improve MCI diagnosis. The mortality in these patients is high even with aggressive surgical/medical management.

Introduction: Mycobacterium Chimaera (MC) infections following cardiovascular surgery are challenging to diagnose given their insidious presentation. We therefore reviewed the various imaging modalities used to diagnose these infections at Mayo Clinic. Methods: Cases from 01/01/2010-06/01/2020 were identified using electronic medical records. Demographics and clinical history were collected. Imaging studies, including transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE), positron emission tomography / computed tomography (PET/CT), cardiac CT (CCT), and cardiac magnetic resonance (CMR) were reviewed. Results: A total of 7 patients (85.7% male) were found. 6 underwent aortic valve replacement and 1 received an aortic composite valve conduit. Surgical dates ranged from 01/2010-12/2018. Mean age at presentation was 63.3 years. Mean time from surgery to symptom onset was 28.0 months. All patients underwent TTE and TEE; prosthetic valve endocarditis was identified in 6 cases between both, while CMR established the diagnosis in 1 case. TTE showed prosthetic valve obstruction in 2 cases and an anterior pseudoaneurysm in 1 case. TEE findings included thickened prosthesis and/or vegetations (n=5), thickened posterior root (n=4), and root abscess (n=3). Among the 3 patients who underwent PET/CT, 2 demonstrated increased fluorodeoxyglucose (FDG) uptake around the aortic prosthesis; in addition, 1 had elevated FDG uptake in the myocardium suggesting myocarditis. 1 patient did not have aortic prosthesis FDG uptake. In the 2 patients who had CCT, 1 showed a pseudoaneurysm that prompted suspicion for endocarditis, and the other revealed a fluid collection adjacent to the aortic valve conduit. 2 patients underwent CMR; 1 had aortic prosthesis thickening and patchy areas of myocardial delayed enhancement suspicious for myocarditis, whereas the other showed vegetation and an aortic root abscess. Conclusion: TTE plus TEE successfully identified MC prosthetic valve endocarditis in most cases with TEE having higher specificity. Advanced imaging techniques are helpful to support the diagnosis and assess for myocardial and/or aortic involvement. Combining these modalities is therefore crucial in unveiling this elusive organism.

AbstractDisseminated blastomycosis in solid organ transplant is uncommon. The diagnosis is usually challenging due to vague clinical presentations, which could lead to a devastating outcome. We reported a unique case of disseminated blastomycosis with laryngeal involvement in a kidney transplant recipient who presented with hoarseness. The diagnosis was made by histopathology and culture of laryngeal mass.

Abstract Background Capnocytopha ga is a gram-negative, facultative anaerobe. Human infection is rare but can lead to devastating outcomes. Capnocytophaga canimorsus can cause sepsis following an animal bite, whereas human-oral–associated Capnocytophaga infections were reported in immunocompromised patients. Current data on these infections are not robust. Our goal is to provide a contemporary description of a unique characteristic of Capnocytophaga infections. Methods We performed a retrospective review of all patients with Capnocytophaga infection from January 2010 to August 2020 at 3 main hospitals of Mayo Clinic in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. We collected baseline demographic data, clinical characteristics, microbiological data, and outcomes of C. canimorsus and human-oral–associated Capnocytophaga infection. Results Among 82 patients with Capnocytophaga infection, 46 patients (56.0%) had bacteremia. The most common species identified in this group was C. sputigena (57.9%), followed by C. canimorsus (34.8%). Patients with human-oral–associated Capnocytophaga bacteremia were often immunocompromised, presented with neutropenic fever, and had worse 6-month all-cause mortality compared to C. canimorsus bacteremia (36.4% vs 6.2%, P = .03). They also had a higher β-lactamase production rate (36.4% vs 0.0%, P = .02). Among patients without bacteremia, the main clinical syndrome was polymicrobial head and neck infections (47.2%). Conclusions Human-oral–associated Capnocytophaga bacteremia occurs primarily in immunocompromised patients, particularly those with hematologic malignancy. In contrast, C. canimorsus bacteremia is more likely to present with community-onset infection related to zoonotic exposure. Human-oral–associated Capnocytophaga infection without bacteremia is frequently isolated in polymicrobial infection; this phenomenon’s significance is yet to be fully understood.

Abstract Background Accurate microbiologic diagnosis is important for appropriate management of infectious diseases. Sequencing-based molecular diagnostics are increasingly used for precision diagnosis of infections. However, their clinical utility is unclear. Methods We conducted a retrospective analysis of specimens that underwent 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) followed by Sanger sequencing at our institution from April 2017 through March 2019. Results A total of 566 specimens obtained from 460 patients were studied. Patients were considered clinically infected or noninfected based on final diagnosis and management. In 17% of patients, 16S rRNA PCR/sequencing was positive and in 5% of patients, this test led to an impact on clinical care. In comparison, bacterial cultures were positive in 21% of patients. Specimens with a positive Gram stain had 12 times greater odds of having a positive molecular result than those with a negative Gram stain (95% confidence interval for odds ratio, 5.2–31.4). Overall, PCR positivity was higher in cardiovascular specimens (37%) obtained from clinically infected patients, with bacterial cultures being more likely to be positive for musculoskeletal specimens (P < .001). 16S rRNA PCR/sequencing identified a probable pathogen in 10% culture-negative specimens. Conclusion 16S rRNA PCR/sequencing can play a role in the diagnostic evaluation of patients with culture-negative infections, especially those with cardiovascular infections.

Abstract Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA.

Abstract Background Mycobacterium septicum is a rapidly growing non-tuberculous mycobacterium. It is a ubiquitous organism capable of causing infections in both healthy and immunocompromised individuals. Only a few cases have been reported to date, and standard therapeutic regimens, and optimal treatment duration have not been defined. Methods We conducted a retrospective chart review of all patients seen at Mayo Clinic in Rochester, MN from July 2014 to March 2020 from whom Mycobacterium septicum was isolated in culture by our clinical microbiology laboratory. Results There were 12 patients identified with M. septicum infection – 7 males and 5 females. The average age was 67 years, with an age range of 48 to 80 years. Seven of 12 isolates obtained were from sputum samples. Only one patient was on immunosuppressive medication. Three cases were considered clinically significant infections for which directed anti-mycobacterial therapy was instituted. In two of these three cases, co-infection with Mycobacterium avium complex (MAC) was seen. Underlying structural lung disease was present in the two cases of pulmonary infections. Peritoneal dialysis catheter-related peritonitis was seen in the third case. All the isolates were susceptible to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX). The isolates were resistant to clarithromycin and doxycycline. Patient Characteristics, Associated M. septicum Illness, and Therapy Provided Antimicrobial Susceptibility Profiles of the Mycobacterium septicum Isolates, MIC (mcg/mL) and Interpretation Patient Demographics and Specimen Source of Mycobacerium septicum Isolates Conclusion M. septicum is an unusual cause of non-tuberculous mycobacterial infection. The presence of a foreign body may increase the risk of infection. Individuals with underlying structural lung disease are also likely to be at increased risk of developing pulmonary infection. Generalized treatment recommendations are limited by the lack of prospective controlled trials; hence, optimal antibiotic regimen and treatment duration have not been firmly established. Susceptibility testing should be performed to guide treatment selection, but the use of combination therapy with potentially empiric agents like amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and TMP-SMX as demonstrated in this small study, can be considered. A high rate of macrolide resistance was noted in our study. Disclosures All Authors: No reported disclosures