Diabetes, SGLT-2 Inhibitors, and Urinary Tract Infection: a Review.

PURPOSE OF REVIEW: The aim of this review is to focus on epidemiology, pathogenesis, risk factors, management, and complications of UTI in people with diabetes as well as reviewing the association of SGLT-2 inhibitors with genitourinary infections. RECENT FINDINGS: Individuals diagnosed with T2DM are more prone to experiencing UTIs and recurrent UTIs compared to individuals without T2DM. T2DM is associated with an increased risk of any genitourinary infections (GUI), urinary tract infections (UTIs), and genital infections (GIs) across all age categories. SGLT2 inhibitors are a relatively new class of anti-hyperglycemic agents, and studies suggest that they are associated with an increased risk of genitourinary infections. The management of diabetes and lifestyle modifications with a patient-centric approach are the most recognized methods for preventing critical long-term complications including genitourinary manifestations of diabetes. The available data regarding the association of SGLT-2 inhibitors with genitourinary infections is more comprehensive compared to that with UTIs. Further research is needed to better understand the mechanisms underlining the association between SGLT-2 inhibitors and genital infections and UTIs.

Molecular Imaging of Infections: Emerging Techniques for Pathogen-Specific Diagnosis and Guided Therapy.

Evaluation of patients that may be infected is challenging. Imaging to identify or localize a site of infection is often limited because of the nonspecific nature of the findings on conventional imaging modalities. Available imaging methods lack the ability to determine if antibiotics are reaching the site of infection and are not optimized to follow response to therapy. Positron emission tomography (PET) is a method by which radiolabeled molecules can be used to detect metabolic perturbations or levels of expression of specific targets. The most common PET agent is the glucose analog 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). 18F-FDG has some applicability to localizing a site of infection, but its lack of specificity limits its usefulness. There is a need for the development of pathogen-specific PET radiotracers to address the imaging shortcomings noted above. Preclinical and clinical progress has been made, but significant challenges remain.

Progress Report: Next-Generation Sequencing, Multiplex Polymerase Chain Reaction, and Broad-Range Molecular Assays as Diagnostic Tools for Fever of Unknown Origin Investigations in Adults.

Even well into the 21st century, infectious diseases still account for most causes of fever of unknown origin (FUO). Advances in molecular technologies, including broad-range polymerase chain reaction (PCR) of the 16S ribosomal RNA gene followed by Sanger sequencing, multiplex PCR assays, and more recently, next-generation sequencing applications, have transitioned from research methods to more commonplace in some clinical microbiology laboratories. They have the potential to supplant traditional microbial identification methods and antimicrobial susceptibility testing. Despite the remaining challenges with these technologies, publications in the past decade justify excitement about the potential to transform FUO investigations. We discuss available evidence using these molecular methods for FUO evaluations, including potential cost-benefits and future directions.

Imaging a Fever-Redefining the Role of 2-deoxy-2-[18F]Fluoro-D-Glucose-Positron Emission Tomography/Computed Tomography in Fever of Unknown Origin Investigations.

Growing evidence suggests that 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-positron emission tomography/computed tomography (PET/CT) is a useful imaging technique for the evaluation of fever of unknown origin (FUO). This imaging technique allows for accurate localization of foci of hypermetabolism based on 18FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. The presence of abnormal uptake can help direct further investigation that may yield a final diagnosis. A lack of abnormal uptake can be reasonably reassuring that these conditions are not present, thereby avoiding unnecessary additional testing. Insurers have not routinely covered outpatient 18FDG-PET/CT for the indication of FUO in the United States. However, data published since 2007 suggest early use in FUO diagnostic evaluations improves diagnostic efficiency and reduces costs. Clinicians and insurers should consider 18FDG-PET/CT as a useful tool when preliminary studies are unrevealing.

Association Between Chronic Use of Immunosuppresive Drugs and Clinical Outcomes From Coronavirus Disease 2019 (COVID-19) Hospitalization: A Retrospective Cohort Study in a Large US Health System.

BACKGROUND: It is unclear whether chronic use of immunosuppressive drugs worsens or improves the severity of coronavirus disease 2019 (COVID-19), with plausible mechanisms for both. METHODS: Retrospective cohort study in 2121 consecutive adults with acute inpatient hospital admission between 4 March and 29 August 2020 with confirmed or suspected COVID-19 in a large academic health system, with adjustment for confounding with propensity score-derived stabilized inverse probability of treatment weights. Chronic immunosuppression was defined as prescriptions for immunosuppressive drugs current at the time of admission. Outcomes included mechanical ventilation, in-hospital mortality, and length of stay. RESULTS: There were 2121 patients admitted with laboratory-confirmed (1967, 93%) or suspected (154, 7%) COVID-19 during the study period, with a median age of 55 years (interquartile range, 40-67). Of these, 108 (5%) were classified as immunosuppressed before COVID-19, primarily with prednisone (>7.5 mg/day), tacrolimus, or mycophenolate mofetil. Among the entire cohort, 311 (15%) received mechanical ventilation; the median (interquartile range) length of stay was 5.2 (2.5-10.6) days, and 1927 (91%) survived to discharge. After adjustment, there were no significant differences in the risk of mechanical ventilation (hazard ratio [HR], .79; 95% confidence interval [CI], .46-1.35), in-hospital mortality (HR, .66; 95% CI, .28-1.55), or length of stay (HR, 1.16; 95% CI, .92-1.47) among individuals with immunosuppression and counterparts. CONCLUSIONS: Chronic use of immunosuppressive drugs was neither associated with worse nor better clinical outcomes among adults hospitalized with COVID-19 in one US health system.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis.

The purpose of this guideline is to provide evidence-based guidance for the most effective strategies for the diagnosis and management of babesiosis. The diagnosis and treatment of co-infection with babesiosis and Lyme disease will be addressed in a separate Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) guideline [1]. Recommendations for the diagnosis and treatment of human granulocytic anaplasmosis can be found in the recent rickettsial disease guideline developed by the Centers for Disease Control and Prevention [2]. The target audience for the babesiosis guideline includes primary care physicians and specialists caring for this condition, such as infectious diseases specialists, emergency physicians, intensivists, internists, pediatricians, hematologists, and transfusion medicine specialists.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis.

The purpose of this guideline is to provide evidence-based guidance for the most effective strategies for the diagnosis and management of babesiosis. The diagnosis and treatment of co-infection with babesiosis and Lyme disease will be addressed in a separate Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) guideline [1]. Recommendations for the diagnosis and treatment of human granulocytic anaplasmosis can be found in the recent rickettsial disease guideline developed by the Centers for Disease Control and Prevention [2]. The target audience for the babesiosis guideline includes primary care physicians and specialists caring for this condition, such as infectious diseases specialists, emergency physicians, intensivists, internists, pediatricians, hematologists, and transfusion medicine specialists.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Palliative care consultation in patients with Staphylococcus aureus bacteremia.

BACKGROUND: Palliative care consultation has shown benefits across a wide spectrum of diseases, but the utility in patients with Staphylococcus aureus bacteremia remains unclear despite its high mortality. AIM: To examine the frequency of palliative care consultation and factors associated with palliative care consult in Staphylococcus aureus bacteremia patients in the United States. DESIGN: A population-based retrospective analysis using the Nationwide Inpatient Sample database in 2014, compiled by the Healthcare Costs and Utilization Project of the Agency for Healthcare Research and Quality. SETTING/SUBJECTS: All inpatients with a discharge diagnosis of Staphylococcus aureus bacteremia (ICD-9-CM codes; 038.11 and 038.12). MEASUREMENTS: Palliative care consultation was identified using ICD-9-CM code V66.7. Patients' baseline characteristics and outcomes were compared between those with and without palliative care consult. RESULTS: A total of 111,320 Staphylococcus aureus bacteremia admissions were identified in 2014. Palliative care consult was observed in 8140 admissions (7.3%). Palliative care consultation was associated with advanced age, white race, comorbidities, higher income, teaching/urban hospitals, Midwest region, Methicillin-resistant Staphylococcus aureus bacteremia and the lack of echocardiogram. Palliative care consult was also associated with shorter but more expensive hospitalizations. Crude mortality was 53% (4314/8140) among admissions with palliative care consult and 8% (8357/10,3180) among those without palliative care consult (p < 0.001). CONCLUSIONS: Palliative care consultation was infrequent during the management of Staphylococcus aureus bacteremia, and a substantial number of patients died during their hospitalizations without palliative care consult. Given the reported benefit in other medical conditions, palliative care consultation may have a role in Staphylococcus aureus bacteremia. Selecting patients who may benefit the most should be explored.

Pathways to Leadership: Reflections of Recent Infectious Diseases Society of America (IDSA) Leaders During Conception and Launch of the Inclusion, Diversity, Access, and Equity Movement Within the IDSA.

Opportunities for leadership in the specialty of infectious diseases (ID) have markedly increased over the last decade, including in newly recognized areas. Commensurate with the expansion of opportunities in ID, pathways to leadership positions within the Infectious Diseases Society of America (IDSA) are expanding as the Society seeks to advance the field for IDSA members. Acknowledging both the importance of diverse leaders to organizational success and shortfalls in diverse representation within IDSA leadership led to concentrated efforts to enhance transparency and opportunities for members to participate broadly in the work of IDSA. Herein, IDSA leaders reflect on their paths to IDSA leadership, hoping to help guide members seeking to partner with the Society. Features identified as important to individual success include mentorship, networking, participation in ID and IDSA volunteer experiences, passion for ID, and working with IDSA staff to advance the programs and initiatives of IDSA on behalf of members.

Infectious Diseases Physicians: Improving and Protecting the Public's Health: Why Equitable Compensation Is Critical.

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees.

Antibiotics for the neurological complications of Lyme disease.

BACKGROUND: Various central nervous system-penetrant antibiotics are bactericidal in vitro and in vivo against the causative agent of Lyme neuroborreliosis (LNB), Borrelia burgdorferi. These antibiotics are routinely used clinically to treat LNB, but their relative efficacy is not clear. OBJECTIVES: To assess the effects of antibiotics for the treatment of LNB. SEARCH METHODS: On 25 October 2016 we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched clinical trial registers on 26 October 2016. We reviewed the bibliographies of the randomized trials identified and contacted the authors and known experts in the field to identify additional published or unpublished data. There were no language restrictions when searching for studies. SELECTION CRITERIA: Randomized clinical trials of antibiotic treatment of LNB in adults and children that compared any antibiotic treatment, including combinations of treatments, versus any other treatment, placebo, or no treatment. We excluded studies of entities considered as post-Lyme syndrome. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified seven randomized studies involving 450 European participants with LNB for inclusion in this systematic review. We found no trials conducted in the United States. Marked heterogeneity among these studies prevented meta-analysis. None of the studies included a placebo control on the initial antibiotic treatment, and only one was blinded. None were delayed-start studies. All were active comparator studies, and most were not adequately powered for non-inferiority comparison. The trials investigated four antibiotics: penicillin G and ceftriaxone in four studies, doxycycline in three studies, and cefotaxime in two studies. One study tested a three-month course of oral amoxicillin versus placebo following initial treatment with intravenous ceftriaxone. One study was limited to children. The trials measured efficacy using heterogeneous physician- or patient-reported outcomes, or both. In some cases cerebrospinal fluid analysis was included as an indirect biomarker of disease and outcome. None of the studies reported on our proposed primary outcome, 'Improvement in a measure of overall disability in the long term (three or more months).' None of the trials revealed any between-group differences in symptom resolution in response to active treatment. In general, treatment was tolerated well. The quality of adverse event reporting, however, was low. AUTHORS' CONCLUSIONS: There is mostly low- to very low-quality clinical evidence from a limited number of mostly small, heterogeneous trials with diverse outcome measures, comparing the relative efficacy of central nervous system-penetrant antibiotics for the treatment of LNB. The few existing randomized studies have limited power and lack consistent and well-defined entry criteria and efficacy endpoints. It is not possible to draw firm conclusions on the relative efficacy of accepted antibiotic drug regimens for the treatment of LNB. The majority of people are reported to have good outcomes, and symptoms resolve by 12 months regardless of the antibiotic used. A minority of participants did not improve sufficiently, and some were retreated. These randomized studies provide some evidence that doxycycline, penicillin G, ceftriaxone, and cefotaxime are efficacious in the treatment of European LNB. No evidence of additional efficacy was observed when, in one study, an initial antibiotic treatment with intravenous ceftriaxone was followed by additional longer treatment with oral amoxicillin. There is a lack of evidence identified through our high-quality search strategy on the efficacy of antibiotics for treatment of LNB in the United States.

Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence.

BACKGROUND: Lyme disease is diagnosed by 2-tiered serologic testing in patients with a compatible clinical illness, but the significance of positive test results in low-prevalence regions has not been investigated. METHODS: We reviewed the medical records of patients who tested positive for Lyme disease with standardized 2-tiered serologic testing between 2005 and 2010 at a single hospital system in a region with little endemic Lyme disease. Based on clinical findings, we calculated the positive predictive value of Lyme disease serology. Next, we reviewed the outcome of serologic testing in patients with select clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial neuropathy, or meningitis). RESULTS: During the 6-year study period 4723 patients were tested for Lyme disease, but only 76 (1.6%) had positive results by established laboratory criteria. Among 70 seropositive patients whose medical records were available for review, 12 (17%; 95% confidence interval, 9%-28%) were found to have Lyme disease (6 with documented travel to endemic regions). During the same time period, 297 patients with a clinical illness compatible with disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%; 95% confidence interval, 0.7%-4.3%) were seropositive, 3 with documented travel and 1 who had an alternative diagnosis that explained the clinical findings. CONCLUSIONS: In this low-prevalence cohort, fewer than 20% of positive Lyme disease tests are obtained from patients with clinically likely Lyme disease. Positive Lyme disease test results may have little diagnostic value in this setting.

Unorthodox alternative therapies marketed to treat Lyme disease.

BACKGROUND: Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. METHODS: Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. RESULTS: More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. CONCLUSIONS: Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful.

Fluoroquinolone resistance in the rectal carriage of men in an active surveillance cohort: longitudinal analysis.

PURPOSE: Rectal swabs can identify men with fluoroquinolone resistant bacteria and decrease the infection rate after transrectal ultrasound guided prostate biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of fluoroquinolone resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance with time. MATERIALS AND METHODS: We evaluated 416 men with prostate cancer on active surveillance who underwent rectal swabs to assess the rate of fluoroquinolone resistance compared to that in men undergoing diagnostic transrectal ultrasound guided prostate biopsy. The chi-square test and Student t-test were used to compare categorical and continuous variables, respectively. Poisson regression analysis was used for multivariate analysis. RESULTS: On the initial swab fluoroquinolone resistance was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221 (24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0% of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p <0.001). Biopsy history was not associated with resistance. Of those with a resistant first swab 62.9% had a resistant second swab and 88.9% of those with 2 resistant swabs showed resistance on the third swab. Of men with a sensitive first swab 10.6% showed resistance on the second swab and 10.6% of those with 2 sensitive swabs had resistant third swabs. CONCLUSIONS: One of 4 men who present for surveillance and diagnostic transrectal ultrasound guided prostate biopsy have rectal flora resistant to fluoroquinolone. Resistance is significantly associated with diabetes but the number of prior biopsies is not. Men with fluoroquinolone resistant flora tend to remain resistant with time.

A systematic review of Borrelia burgdorferi morphologic variants does not support a role in chronic Lyme disease.

BACKGROUND: Much of the controversy that surrounds Lyme disease pertains to whether it produces prolonged, treatment-refractory infection, usually referred to as chronic Lyme disease. Some have proposed that round morphologic variants of Borrelia burgdorferi, known variably as "cyst forms" and "L-forms," are responsible for the pathogenesis of chronic Lyme disease. We have undertaken a systematic review of the literature to determine if there is a documented role of these variants in Lyme disease pathogenesis or in syndromes compatible with chronic Lyme disease. METHODS: Two systematic literature searches were performed to identify studies in which round morphologic variants of B. burgdorferi have been described in situ in human specimens. RESULTS: Our primary literature search identified 6 studies that reported round morphologic variants of B. burgdorferi in specimens obtained from 32 total patients. No study described these forms in patients who had purely subjective symptom complexes (eg, fatigue or pain). No study investigated a causal relationship between morphologic variants and clinical disease or evaluated treatment of morphologic variants in vivo. Of 29 additional studies that described the morphology of B. burgdorferi from patients with Lyme disease, the organism was invariably described as having spirochetal morphology. CONCLUSIONS: In the context of the broader medical literature, it is not currently possible to ascribe a pathogenic role to morphologic variants of B. burgdorferi in either typical manifestations of Lyme disease or in other chronic disease states that are often labeled chronic Lyme disease. There is no clinical literature to justify specific treatment of B. burgdorferi morphologic variants.

The first US domestic report of disseminated Mycobacterium avium complex and anti-interferon-γ autoantibodies.

INTRODUCTION: Anti-interferon-γ (IFNγ) autoantibodies have been associated with disseminated mycobacterial infections, mostly in patients from Southeast Asia. PURPOSE: We studied an American-born, Caucasian female with M. avium complex infection of the subglottic mucosa and brain for underlying etiologies of infection. METHODS: Plasma was screened for anticytokine autoantibodies using a Luminex-based approach. The ability of patient plasma to block IFNγ-induced STAT1 phosphorylation in normal blood cells was evaluated by flow cytometry with intracellular staining. Plasma inhibition of IFNγ production and IFNγ-induced cytokines in normal and patient blood cells washed of autologous plasma was also evaluated. RESULTS: Patient plasma contained high-titer IgG anti-IFNγ autoantibodies, primarily of the IgG1 subclass. Patient but not control plasma prevented IFNγ-induced STAT1 phosphorylation and expression of the IFNγ-inducible cytokines tumor necrosis factor (TNF) α and interleukin (IL)-12 in normal blood cells. Patient blood cells washed free of autologous plasma demonstrated normal IFNγ production and response. CONCLUSIONS: Disseminated nontuberculous mycobacterial infections should always prompt immune evaluation. This first case of disseminated nontuberculous mycobacterial infection and anti-IFNγ autoantibodies in an American-born Caucasian suggests that anti-cytokine autoantibodies are not racially or regionally restricted.