Disseminated Mycobacterium chimaera infection successfully treated with a clofazimine-containing regimen and long-term follow-up after discontinuing treatment.

Mycobacterium chimaera is a slow-growing member of the Mycobacterium avium complex. It can contaminate tap water and has been detected in water tanks of heater-cooler devices used during open-heart surgery. Herein we report a case of a 67-year-old- male with disseminated M. chimaera infection who presented with fevers, significant weight loss and was found to have bacteremia with prosthetic valve endocarditis, chorioretinitis, bone marrow and splenic granulomas two years after an open-heart surgery. He developed multiple drug adverse events over the course of treatment but was successfully treated using a clofazimine containing regimen along with aortic valve replacement. He has remained symptom-free with no signs of recurrence three years after completion of antimicrobials. Clofazimine is an effective alternative that can be used as part of a multi-drug regimen in M. chimaera infection when there is resistance to first-line drugs or when adverse drug reactions occur.

Does Antimicrobial Prophylaxis in Patients with Specific Comorbidities Reduce the Risk of Infection after Simple Cystourethroscopy?

INTRODUCTION: We evaluated whether antimicrobial prophylaxis decreases rates of post-procedural infection (urinary tract infection or sepsis) after simple cystourethroscopy for patients with specific comorbidities. METHODS: We utilized Epic® reporting software to conduct a retrospective review of all simple cystourethroscopy procedures performed by providers in our urology department from August 4, 2014 to December 31, 2019. Data collected included patient comorbidities, antimicrobial prophylaxis administration and incidence of post-procedural infection. Mixed effects logistic regression models were utilized to estimate the effects of antimicrobial prophylaxis and patient comorbidities on the odds of post-procedural infection. RESULTS: Antimicrobial prophylaxis was given for 7,001 (78%) of 8,997 simple cystourethroscopy procedures. Overall, 83 (0.9%) post-procedural infections occurred. The estimated odds of post-procedural infection were lower when antimicrobial prophylaxis was given compared to those without prophylaxis (OR 0.51, 95% CI 0.35-0.76; p <0.01). The number needed to treat with antimicrobial prophylaxis to prevent 1 post-procedural infection was 100. None of the comorbidities evaluated showed significant benefit from antimicrobial prophylaxis for prevention of post-procedural infection. CONCLUSIONS: Overall, the rate of post-procedural infection after simple office cystourethroscopy was low (0.9%). Though antimicrobial prophylaxis decreased the odds of post-procedural infection overall, the number needed to treat was high (100). Antibiotic prophylaxis was not shown to significantly reduce the risk of post-procedural infection in any of the comorbidity groups we evaluated. These findings suggest that the comorbidities evaluated in this study should not be used to recommend antibiotic prophylaxis for simple cystourethroscopy.

Asymptomatic Pre-Operative COVID-19 Screening for Essential and Elective Surgeries: Early Results of Universal Screening at a Midwestern Academic Medical Center.

BACKGROUND: During the novel Coronavirus 2019 (COVID-19) worldwide pandemic, viral testing has largely focused on patients presenting with fever and respiratory symptoms. Although Centers for Disease Control has reported 1,551,095 cases in the United States as of May 21, 2020, asymptomatic infection rates remain unknown within the U.S., especially in geographically disparate regions. METHODS: On April 7, 2020 our hospital established universal SARS-CoV-2 screening using RT-PCR RNA detection from nasopharyngeal swabs from asymptomatic patients prior to essential and elective surgeries. This study included 1,997 asymptomatic patients undergoing surgical procedures and 1,797 admitted for medical management at a Midwestern academic hospital between April 7, 2020 and May 21, 2020. RESULTS: As of May 21, asymptomatic testing for SARS-CoV-2 infection had been completed for 1,997 surgical patients and 1,797 non-surgical patients. Initial testing was positive in 26 patients, with an additional four positive tests occurring during repeat testing when greater than 48 hours had elapsed since initial testing. Overall asymptomatic infection rate was 0.79%. Asymptomatic infection rate was significantly lower in surgical patients (0.35% vs. 1.28%, p=0.001). Surgical patients tended to be older than non-surgical patients, although this was not statistically significant (51, IQR 27-65 vsx 46, IQR 28-64, p=0.057). Orthopedic surgery patients were significantly younger than those from other surgical services (42 vs. 53 yrs, p<0.001), however orthopedic and non-orthopedic surgical patients had similar asymptomatic infection rates (0.70% vs. 0.25%, p=0.173). CONCLUSION: Among asymptomatic patients tested at a Midwestern academic medical center, 0.79% were infected with SARS-CoV-2 virus. These findings will help guide screening protocols at medical centers while providing essential and elective procedures during the COVID-19 pandemic. While the asymptomatic infection rate was low, this data substantiates the threat of asymptomatic infections and potential for community viral spread. These results may not be generalizable to large urban population centers or areas with high concentrations of COVID-19, each region must use available data to evaluate the risk-benefit ratio of universal testing vs universal contact precautions.Level of Evidence: IV.

MRSA strains with distinct accessory genes predominate at different ages in cystic fibrosis.

RATIONALE: Methicillin resistant Staphylococcus aureus (MRSA) is prevalent and consequential in cystic fibrosis (CF). Whole genome sequencing (WGS) could reveal genomic differences in MRSA associated with poorer outcomes or detect MRSA transmission. OBJECTIVES: To identify MRSA genes associated with low lung function and potential MRSA transmission in CF. METHODS: We collected 97 MRSA isolates from 74 individuals with CF from 2017 and performed short-read WGS. We determined sequence type (ST) and the phylogenetic relationship between isolates. We aligned accessory genes from 25 reference genomes to genome assemblies, classified isolates by accessory gene content, and correlated the accessory genome to clinical outcomes. RESULTS: The most prevalent ST were ST5 (N = 55), ST8 (N = 15), and ST105 (N = 14). Closely related MRSA strains were shared by family members with CF, but rarely between unrelated individuals. Three clusters of MRSA were identified by accessory genome content. Cluster A, including ST5 and ST105, was highly prevalent at all ages. Cluster B, including ST8, was more limited to younger patients. Cluster C included 6 distantly related strains. Patients 20 years old and younger infected with Cluster A had lower forced expiratory volume in the first second (FEV1 ) and higher sputum biomass compared to similar-aged patients with Cluster B. CONCLUSIONS: In this CF cohort, we identified MRSA subtypes that predominate at different ages and differ by accessory gene content. The most prevalent cluster of MRSA, including ST5 and ST105, was associated with lower FEV1 . ST8 MRSA was more common in younger patients and thus has the potential to rise in prevalence as these patients age.

Ocular Actinomycosis Mimicking Meningioma.

Orbital actinomycosis is an unusual clinical manifestation of orbital infection caused by Actinomyces species. Herein we report a case of orbital actinomycosis in a 67-year-old woman with recurrent swelling and erythema around her left eye with an orbital mass initially thought to be a meningioma.

Characteristics of Nontuberculous Mycobacterial Infections at a Midwestern Tertiary Hospital: A Retrospective Study of 365 Patients.

BACKGROUND: The prevalence of infections due to nontuberculous mycobacteria (NTM) is increasing worldwide, yet little is known about the epidemiology and pathophysiology of these ubiquitous environmental organisms. Pulmonary disease due to Mycobacterium avium complex is most prevalent, but many other NTM species can cause disease in virtually any organ system. As NTM becomes an increasingly common cause of morbidity and mortality, more information is needed about the epidemiology of NTM disease. METHODS: We conducted a retrospective chart review of all patients with cultures that grew NTM at a Midwestern tertiary hospital from 1996 to 2017. Information on demographics, medical history, clinical findings, treatment, and outcome was obtained from medical records of all NTM isolates. American Thoracic Society/Infectious Diseases Society of America criteria were used to define pulmonary NTM infections. RESULTS: We identified 1064 NTM isolates, 365 of which met criteria for NTM infection. Pulmonary cases predominated (185 of 365; 50.7%), followed by skin/soft tissue (56 of 365; 15.3%), disseminated (40 of 365; 11%), and lymphatic (28 of 365; 7.7%) disease. Mycobacterium avium complex was the most common species (184 of 365; 50.4%). Individuals aged >50 years were most affected (207 of 365; 56.7%). Common comorbidities included structural lung disease (116 of 365; 31.8%), use of immunosuppressive medications (78 of 365; 21.4%), malignancy (59 of 365; 16.2%), and human immunodeficiency virus (42 of 365; 11.5%). CONCLUSIONS: This large cohort provides information on the demographics, risk factors, and disease course of patients with pulmonary and extrapulmonary NTM infections. Most patients had medical comorbidities that resulted in anatomic, genetic, or immunologic risk factors for NTM infection. Further population-based studies and increased disease surveillance are warranted to further characterize NTM infection prevalence and trends.

Mixed Actinomyces israelii and Aggregatibacter actinomycetemcomitans infection causing empyema necessitatis and multiple skin abscesses in an immunocompetent patient.

A 45-year-old- man presented with left chest wall pain, swelling and cough. Over a 2-month period he developed abscesses in the right foot, right anterior thigh, left buttock and left chest. Incision and drainage of the soft tissue abscesses and video-assisted thoracoscopic surgery to drain the loculated empyema contiguous with the chest wall abscess were performed as surgical management. Gram stain showed beaded Gram-positive rods and the culture initially grew Aggregatibacter actinomycetemcomitans and Eikenella corrodens Pathological evaluation of the pleura showed sulfur granules and organisms consistent with Actinomyces spp. on Gomori methenamine silver stain; Actinomyces israelii was recovered in culture with extended incubation. The patient was treated for 3 weeks with ceftriaxone and oral metronidazole, followed by oral amoxicillin. Culture of A. actinomycetemcomitans with other findings consistent with actinomycosis warrants 6-12 months of antibiotic therapy.

Angioinvasive fungal infections impacting the skin: Diagnosis, management, and complications.

As discussed in the first article in this continuing medical education series, angioinvasive fungal infections pose a significant risk to immunocompromised and immunocompetent patients alike, with a potential for severe morbidity and high mortality. The first article in this series focused on the epidemiology and clinical presentation of these infections; this article discusses the diagnosis, management, and potential complications of these infections. The mainstay diagnostic tests (positive tissue culture with histologic confirmation) are often supplemented with serum biomarker assays and molecular testing (eg, quantitative polymerase chain reaction analysis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry) to ensure proper speciation. When an angioinvasive fungal infection is suspected or diagnosed, further workup for visceral involvement also is essential and may partially depend on the organism. Different fungal organisms have varied susceptibilities to antifungal agents, and knowledge on optimal treatment regimens is important to avoid the potential complications associated with undertreated or untreated fungal infections.

Angioinvasive fungal infections impacting the skin: Background, epidemiology, and clinical presentation.

Angioinvasive fungal infections cause significant morbidity and mortality because of their propensity to invade blood vessel walls, resulting in catastrophic tissue ischemia, infarct, and necrosis. While occasionally seen in immunocompetent hosts, opportunistic fungi are emerging in immunosuppressed hosts, including patients with hematologic malignancy, AIDS, organ transplant, and poorly controlled diabetes mellitus. The widespread use of antifungal prophylaxis has led to an "arms race" of emerging fungal resistance patterns. As the at-risk population expands and new antifungal resistance patterns develop, it is critical for dermatologists to understand and recognize angioinvasive fungal pathogens, because they are often the first to encounter the cutaneous manifestations of these diseases. Rapid clinical recognition, histopathologic, and culture confirmation can help render a timely, accurate diagnosis to ensure immediate medical and surgical intervention. Superficial dermatophyte infections and deep fungal infections, such as blastomycosis and histoplasmosis, have been well characterized within the dermatologic literature, and therefore this article will focus on the severe infections acquired by angioinvasive fungal species, including an update on new and emerging pathogens. In the first article in this continuing medical education series, we review the epidemiology and cutaneous manifestations. The second article in the series focuses on diagnosis, treatment, and complications of these infections.

Failure of Risk-Adjustment by Test Method for C. difficile Laboratory-Identified Event Reporting.

Using an algorithm including both enzyme immunoassay (EIA) and nucleic acid amplification (NAAT) for Clostridium difficile infection (CDI) diagnosis, we found that the use of NAAT versus EIA almost doubled our hospital-onset CDI laboratory-identified (LabID) event standardized infection ratio (SIR). We recommend that the current risk adjustment approach be modified. Infect Control Hosp Epidemiol 2016:1-3.

Methylotroph Infections and Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.

POSITIVE TEST FOR ANTITHYROGLOBULIN ANTIBODIES DUE TO ADMINISTRATION OF IMMUNOGLOBULIN REPLACEMENT THERAPY IN A PATIENT WITH THYROID CANCER.

OBJECTIVE: Thyroglobulin (Tg) is used as a tumor marker to monitor differentiated thyroid cancer progression and recurrence. However, Tg measured by standard immunoassay (IMA) is not a reliable marker in the presence of anti-Tg antibodies (TgAbs) due to interference that may result in either false-positive or false-negative results. TgAbs levels can be high due to thyroid cancer and also exogenous immunoglobulin (Ig) administration, thus making it difficult to identify differentiated thyroid cancer recurrence. METHODS: We present an example of elevated TgAbs due to subcutaneous Ig (SCIg) administration in a patient with thyroid cancer. RESULTS: A 57-year-old male was diagnosed with stage I papillary thyroid cancer (PTC). His TgAbs were negative prior to the diagnosis of thyroid cancer and became positive after thyroidectomy and radioactive iodine administration. A detailed work-up including a whole body scan did not reveal recurrent disease. He had been diagnosed with common variable immune deficiency (CVID) and dermatomyositis at the age of 50 and was started on immunoglobulin (Ig) replacement therapy shortly after diagnosis. His Tg was negative when assessed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Therefore, elevated TgAb titers were attributed to concomitant SCIg treatment. We also demonstrated that SCIg treatment had TgAb activity that was removed by protein A column treatment. Dilutions of SCIg medication also caused positive IgG serologies for cytomegalovirus and herpes simplex, measles, mumps, rubella, and varicella zoster viruses. CONCLUSION: An exogenous source of TgAbs from SCIg led to extensive imaging work-up to assess for PTC recurrence. LC-MS/MS is a conceptually attractive approach to overcome TgAb interference with Tg IMA measurement.

Myocardial infection due to Fusobacterium nucleatum.

Fusobacterium nucleatum is an anaerobic gram-negative bacillus, which inhabits the oropharynx, gastrointestinal tract, and female genital tract. Infections classically affect the head and neck. We report a patient with a myocardial mass due to F. nucleatum, initially thought to be a neoplasm, and discuss anaerobic cardiac infections.

Enterococcus faecalis inhibits superantigen toxic shock syndrome toxin-1-induced interleukin-8 from human vaginal epithelial cells through tetramic acids.

The vaginal mucosa can be colonized by many bacteria including commensal organisms and potential pathogens, such as Staphylococcus aureus. Some strains of S. aureus produce the superantigen toxic shock syndrome toxin-1, which can penetrate the vaginal epithelium to cause toxic shock syndrome. We have observed that a female was mono-colonized with Enterococcus faecalis vaginally as tested in aerobic culture, even upon repeated culture for six months, suggesting this organism was negatively influencing colonization by other bacteria. In recent studies, we demonstrated an "outside-in" mechanism of cytokine signaling and consequent inflammation that facilitates the ability of potential pathogens to initiate infection from mucosal surfaces. Thus, we hypothesized that this strain of E. faecalis may make anti-inflammatory factors which block disease progression of more pathogenic organisms. E. faecalis MN1 inhibited interleukin-8 production from human vaginal epithelial cells in response to the vaginal pathogens Candida albicans, Gardnerella vaginalis, and Neisseria gonorrhoeae, as well as to toxic shock syndrome toxin-1. We further demonstrated that this organism secretes two tetramic acid compounds which appear responsible for inhibition of interleukin-8 production, as well as inhibition of T cell proliferation due to toxic shock syndrome toxin-1. Microbicides that include anti-inflammatory molecules, such as these tetramic acid compounds naturally produced by E. faecalis MN1, may be useful in prevention of diseases that develop from vaginal infections.

Intra-individual variability in serum hepcidin precludes its use as a marker of iron status in hemodialysis patients.

An accurate assessment of iron status in dialysis patients is important because both anemia and overtreatment with erythropoiesis-stimulating agents are associated with poor clinical outcomes. We have previously shown that both analytical and intra-individual (biological) variability in serum ferritin limits its utility as a proxy for iron stores in patients in this setting. As hepcidin is a direct regulator of iron status, its measurement might be useful for monitoring patients with iron dysregulation. We assessed short-term intra-individual variation of serum hepcidin in 28 patients with stable chronic kidney disease on hemodialysis. The intra-individual variability for serum hepcidin ranged from 9-79% during an initial 2-week to 12-85% over a 6-week period. The concentration of serum hepcidin was significantly correlated with serum C-reactive protein levels over the 6-week study period. Hence, significant intra-individual variability of hepcidin is likely dependent on short-term fluctuations in the inflammatory state. Thus, our results suggest that short-term measurement of serum hepcidin should not be used to guide clinical decisions regarding management of iron status in chronic hemodialysis patients.

Variability of ferritin measurements in chronic kidney disease; implications for iron management.

Serum ferritin levels are a proxy measure of iron stores; and existing guidelines for managing anemia in hemodialysis patients suggest that serum ferritin concentrations should be maintained at >200 ng/ml. The KDOQI recommendations further state there is insufficient evidence advocating routine intravenous iron when ferritin levels exceed 500 ng/ml. Here we determined the interassay differences and short-term intraindividual variability of serum ferritin measurements in patients on chronic hemodialysis to illustrate how these variances may affect treatment decisions. Intermethod variations of up to 150 ng/ml were found comparing six commonly used ferritin assays that evaluated thirteen pools of serum from hemodialysis and nonhemodialysis patients. The intraindividual variability for ferritin in 60 stable hemodialysis patients ranged between 2-62% measured over an initial two-week period and from 3-52% when factored over a six-week period. Our results suggests that single serum ferritin values should not be used to guide clinical decisions regarding treatment of chronic hemodialysis patients with intravenous iron due to significant analytical and intraindividual variability.