Extra-urogenital infection by Mycoplasma hominis in transplant patients: two case reports and literature review.

BACKGROUND: Mycoplasma hominis is a facultative anaerobic bacterium commonly present in the urogenital tract. In recent years, M. hominis has increasingly been associated with extra-urogenital tract infections, particularly in immunosuppressed patients. Detecting M. hominis in a diagnostic laboratory can be challenging due to its slow growth rate, absence of a cell wall, and the requirements of specialized media and conditions for optimal growth. Consequently, it is necessary to establish guidelines for the detection of this microorganism and to request the appropriate microbiological work-up of immunosuppressed patients. CASE PRESENTATION: We hereby present two cases of solid organ transplant patients who developed M. hominis infection. Microscopic examination of the bronchial lavage and pleural fluid showed no microorganisms. However, upon inoculating the specimens onto routine microbiology media, the organism was successfully identified and confirmation was performed using 16S rDNA sequencing. Both patients received appropriate treatment resulting in the resolution of M. hominis infection. CONCLUSIONS: The prompt detection of M. hominis in a clinical specimen can have a significant impact on patient care by allowing for early intervention and ultimately resulting in more favorable clinical outcomes, especially in transplant patients.

Early Results from Severe Acute Respiratory Syndrome Coronavirus 2 Polymerase Chain Reaction Testing of Healthcare Workers at an Academic Medical Center in New York City.

Coronavirus disease 2019 (COVID-19) reverse-transcription polymerase chain reaction employee testing was implemented across New York University Langone Health. Over 8 weeks, 14 764 employees were tested; 33% of symptomatic employees, 8% of asymptomatic employees reporting COVID-19 exposure, and 3% of employees returning to work were positive. Positivity rates declined over time, possibly reflecting the importance of community transmission and efficacy of personal protective equipment.

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.

SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection.

Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS-CoV-2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19). Serum samples were collected 1-59 days post-onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR-confirmed COVID-19 and samples collected during convalescence, 35-57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS-CoV-2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.

Performance of Abbott ID Now COVID-19 Rapid Nucleic Acid Amplification Test Using Nasopharyngeal Swabs Transported in Viral Transport Media and Dry Nasal Swabs in a New York City Academic Institution.

The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real-time reverse transcription-PCR (RT-PCR) platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. The two platforms demonstrate comparable performances; however, the run times for each assay are 3.5 h and 45 min, respectively. In search for a platform with a shorter turnaround time, we sought to evaluate the recently released Abbott ID Now COVID-19 assay, which is capable of producing positive results in as little as 5 min. We present here the results of comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID Now. Regardless of method of collection and sample type, Abbott ID Now COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.

Post-COVID-19 inflammatory syndrome manifesting as refractory status epilepticus.

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.

Rapid and Extensive Expansion in the United States of a New Multidrug-resistant Escherichia coli Clonal Group, Sequence Type 1193.

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant Escherichia coli clone-sequence type (ST) 1193-resistant to fluoroquinolones (100%), trimethoprim-sulfamethoxazole (55%), and tetracycline (53%). ST1193 is associated with younger adults (age <40 years) and currently comprises a quarter of fluoroquinolone-resistant clinical E. coli urine isolates.

Limitations and Confusing Aspects of Diagnostic Testing for Neurologic Lyme Disease in the United States.

In the United States, laboratories frequently offer multiple different assays for testing of cerebrospinal fluid (CSF) samples to provide laboratory support for the diagnosis of central nervous system Lyme disease (CNSLD). Often included among these diagnostic tests are the same enzyme immunoassays and immunoblots that are routinely used to detect the presence of antibodies to Borrelia burgdorferi in serum. However, performing these assays on CSF alone may yield positive results simply from passive diffusion of serum antibodies into the CSF. In addition, such tests are only U.S. Food and Drug Administration cleared and well validated for testing serum, not CSF. When performed using CSF, positive results from these assays do not establish the presence of intrathecal antibody production to B. burgdorferi and therefore should not be offered. The preferred test to detect intrathecal production of antibodies to B. burgdorferi is the antibody index assay, which corrects for passive diffusion of serum antibodies into CSF and requires testing of paired serum and CSF collected at approximately the same time. However, this assay also has limitations and should only be used to establish a diagnosis of CNSLD in conjunction with patient exposure history, clinical presentation, and other laboratory findings.

Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome.

The extended-spectrum-ß-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying both blaCTX-M and blaKPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, blaCTX-M and blaKPC were carried on two different plasmids. In contrast, CN1 had one copy of blaKPC-2 and three copies of blaCTX-M-15 integrated in the chromosome, for which the blaCTX-M-15 genes were linked to an insertion sequence, ISEcp1, whereas the blaKPC-2 gene was in the context of a Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn4401a-blaKPC-2-prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)-cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR-cas in K. pneumoniae strains and suggested that the evolving CRISPR-cas, with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of blaCTX-M and blaKPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae Additionally, the implications from this study also raise concerns for the application of a CRISPR-cas strategy against antimicrobial resistance.

Utility of serodiagnostics designed for use in the United States for detection of Lyme borreliosis acquired in Europe and vice versa.

Although two-tier testing is standard practice in both the United States and Europe for the serologic diagnosis of Lyme borreliosis (LB), the test kits generally differ. The purpose of this study was to determine if the testing used in the United States will detect LB acquired in Europe and vice versa. Testing was performed on a convenience sample of archived sera from 40 LB patients from Austria and 39 from the United States, using first- and second-tier test kits from both the United States and Europe. The sensitivity of four first-tier tests from Europe and two first-tier tests from the United States was similar. Thus, two-tier testing was compared to the C6 ELISA as the first-tier test, since it is licensed in both the United States and Europe. The sensitivity of C6 two-tier testing with US assays was 9/40 (22.5 % [95 % CI 10.8-38.5 %]) for detection of LB acquired in Europe, and just 20.0 % (95 % CI 2.5-55.6 %) in the ten European patients with neurologic involvement. These results differed significantly from the sensitivity of European C6 two-tier testing that was 70.0 % (95 % CI 53.5-83.4 %) overall (p < 0.001) and 90.0 % (95 % CI 55.5-99.7 %) for the European patients with neurologic manifestations specifically (p = 0.016). In contrast, the sensitivity of European and US C6 two-tier testing was similar for detection of LB acquired in the United States. Two-tier serologic testing with the US test kits may be unsatisfactory for detection of LB acquired in Europe. First-tier testing with an assay such as the C6 ELISA should be considered as a stand-alone diagnostic strategy in such cases.

Lyme disease and human granulocytic anaplasmosis coinfection: impact of case definition on coinfection rates and illness severity.

BACKGROUND: Lyme disease is transmitted by the bite of the Ixodes scapularis tick, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Conflicting data exist on the frequency of coinfection and on whether Lyme-HGA coinfected patients have more symptoms than patients with Lyme disease alone. METHODS: Blood culture and serology were used to detect HGA infection in patients with early Lyme disease who presented with erythema migrans. The rate of coinfection was determined using different definitions. The clinical and laboratory features of Lyme-HGA coinfection were compared with that of the individual infections. RESULTS: Among 311 patients with erythema migrans, the frequency of coinfection with HGA varied from 2.3% to 10.0%, depending on the definition used (P < .001). Only 1 of 4 groups with presumed coinfection had significantly more symptoms than patients with Lyme disease alone P < .05. High fever and cytopenia were less common in Lyme-HGA coinfection than in patients with HGA alone. CONCLUSION: The results of this study indicate that how HGA is defined in patients with early Lyme disease has an impact on the apparent rate of coinfection and the severity of illness. The findings also suggest that HGA may be less severe than is usually believed, suggesting the existence of referral bias in testing patients preferentially who present with high fever or cytopenia.

Differences and similarities between culture-confirmed human granulocytic anaplasmosis and early lyme disease.

Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms (P = 0.003) and had a higher body temperature on presentation (P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho = 0.389, P = 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease.

Vertical transmission of Babesia microti, United States.

Babesiosis is usually acquired from a tick bite or through a blood transfusion. We report a case of babesiosis in an infant for whom vertical transmission was suggested by evidence of Babesia spp. antibodies in the heel-stick blood sample and confirmed by detection of Babesia spp. DNA in placenta tissue.

Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients With Community-Acquired Pneumonia Admitted Within a Large Academic Health System.

BACKGROUND: Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. METHODS: This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients' outcomes. RESULTS: We evaluated 910 patients, 121 (13.3%) of whom were PUAT positive. No difference in baseline characteristics, including severity of illness, was observed between groups. Initial de-escalation occurred in 82.9% and 81.2% of PUAT-positive and -negative patients, respectively (P = .749). Median time to de-escalation was shorter in the PUAT-positive group (1 [interquartile range {IQR}, 0-2] day vs 1 [IQR, 1-2] day, P = .01). Within 24 hours of PUAT, more patients in the PUAT-positive group had atypical coverage discontinued (61.3% vs 47.2%, P = .026) without difference in methicillin-resistant Staphylococcus aureus (MRSA) agent discontinuation (or antipseudomonal de-escalation). Among the PUAT-positive group, unadjusted analysis demonstrated shorter median length of stay in patients who were de-escalated compared to those who were not (6 [IQR, 4-10] vs 8 [IQR, 7-12] days, P = .0005), without difference in the incidence of Clostridioides difficile, in-hospital mortality, or 30-day infection-related readmission. CONCLUSIONS: We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.

Rate and consequences of missed Clostridioides (Clostridium) difficile infection diagnosis from nonreporting of Clostridioides difficile results of the multiplex GI PCR panel: experience from two-hospitals.

INTRODUCTION: It is common among microbiology laboratories to blind the Clostridioides difficile (C. difficile) BioFire FilmArray GI Panel result in fear of overdiagnosis. METHODS: We examined the rate of missed community-onset C. difficile infection (CDI) diagnosis and associated outcomes. Adult patients with FilmArray GI Panel positive for C. difficile on hospital admission who lacked dedicated C. difficile testing were included. RESULTS: Among 144 adults with a FilmArray Panel positive for C. difficile, 18 did not have concurrent dedicated C. difficile testing. Eight patients were categorized as possible, 5 as probable and 4 as definite cases of missed CDI diagnosis. We observed associated delays in initiation of appropriate therapy, intensive care unit admissions, hospital readmissions, colorectal surgery and death/discharge to hospice. Five out of 17 lacked risk factors for CDI. CONCLUSION: The practice of concealing C. difficile FilmArray GI Panel results needs to be reconsidered in patients presenting with community-onset colitis.

A new genetic approach to distinguish strains of Anaplasma phagocytophilum that appear not to cause human disease.

Genetic diversity of Anaplasma phagocytophilum was assessed in specimens from 16 infected patients and 16 infected Ixodes scapularis ticks. A region immediately downstream of the 16S rRNA gene, which included the gene encoding SdhC, was sequenced. For the A. phagocytophilum strains from patients no sequence differences were detected in this region. In contrast, significantly fewer ticks had a sequence encoding SdhC that was identical to that of the human strains (11/16 vs. 16/16, p = 0.04). This variation is consistent with the premise that not all A. phagocytophilum strains present in nature are able to cause clinical illness in humans. A strain referred to as A. phagocytophilumVariant-1 that is regarded as non-pathogenic for humans was previously described using a different typing method. Data from the current study suggest that both typing methods are identifying the same non-pathogenic strains.

Effect of Vancomycin on the Gut Microbiome and Plasma Concentrations of Gut-Derived Uremic Solutes.

INTRODUCTION: Declining renal function results in the accumulation of solutes normally excreted by healthy kidneys. Data suggest that some of the protein-bound solutes mediate accelerated cardiovascular disease. Many of the poorly dialyzable protein-bound uremic retention solutes are products of gut bacterial metabolism. METHODS: We performed a blinded-randomized controlled trial comparing the changes in plasma concentrations of a panel of protein-bound solutes and microbiome structure in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 12 weeks in a cohort of stable patients with end-stage kidney disease. We also examined the pattern of recovery of the solutes and gut microbiome over 12 weeks of placebo administration following vancomycin. RESULTS: We enrolled 15 subjects. Ten subjects provided sufficient plasma and stool samples to permit us to examine the effect of vancomycin on plasma solute levels. We showed that a weekly dose of vancomycin resulted in a reduction in the plasma concentration of 7 colon-derived solutes. We described a significant effect of vancomycin on the microbiome structure with a decrease in alpha diversity and change in beta diversity. Multiple taxa decreased with vancomycin including genera Clostridium and Bacteroides. We demonstrated microbiome recovery after stopping vancomycin. However, recovery in the solutes was highly variable between subjects. CONCLUSIONS: We demonstrated that microbiome suppression using vancomycin resulted in changes in multiple gut-derived uremic solutes. Future studies are needed to address whether reduction in those uremic solutes results in improvement of cardiovascular outcomes in ESKD patients.

The New York State SARS-CoV-2 Testing Consortium: Regional Communication in Response to the COVID-19 Pandemic.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Through the length of the pandemic, the consortium has been a critical mechanism for sharing experience and best practices in dealing with issues including the following: instrument platforms, sample sources, test performance, pre- and post-analytical issues, supply chain, institutional testing capacity, pooled testing, biospecimen science, and research. The consortium also has been a mechanism for staying abreast of state and municipal policies and initiatives, and their impact on institutional and laboratory operations. The experience of this consortium may be of value to current and future laboratory professionals and policy-makers alike, in dealing with major events that impact regional laboratory services.

Clinical Practice Guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 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.