A decade of clinical microbiology: top 10 advances in 10 years: what every infection preventionist and antimicrobial steward should know.

The past 10 years have brought paradigm-shifting changes to clinical microbiology. This paper explores the top 10 transformative innovations across the diagnostic spectrum, including not only state of the art technologies but also preanalytic and post-analytic advances. Clinical decision support tools have reshaped testing practices, curbing unnecessary tests. Innovations like broad-range polymerase chain reaction and metagenomic sequencing, whole genome sequencing, multiplex molecular panels, rapid phenotypic susceptibility testing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry have all expanded our diagnostic armamentarium. Rapid home-based testing has made diagnostic testing more accessible than ever. Enhancements to clinician-laboratory interfaces allow for automated stewardship interventions and education. Laboratory restructuring and consolidation efforts are reshaping the field of microbiology, presenting both opportunities and challenges for the future of clinical microbiology laboratories. Here, we review key innovations of the last decade.

A case report of a prostate cancer metastasis in the pancreas exhibiting vascular encasement.

We report a patient who presented with a 4-month history of intermittent epigastric pain. Computed tomography (CT) angiography of the abdomen demonstrated a stenotic celiac trunk but also encasement of the common proper hepatic artery, gastroduodenal artery, and proper hepatic artery by an ill-defined hypoattenuating mass of the pancreatic head. Biopsy confirmed metastatic prostate cancer to the pancreas that occurred 4 years after radiation and androgen deprivation therapy. A follow-up staging study demonstrated an osseous metastasis at the T4 spinous process. This case demonstrates an unusual case of prostate metastasis to the pancreas with the involvement of a main abdominal vessel. With treatment improvements leading to longer survival rates from prostate cancer, radiologists should be aware of atypical metastases that may arise in the long term.

The diagnostic and clinical utility of microbial cell-free DNA sequencing in a real-world setting.

Microbial cell free DNA sequencing is increasingly used for diagnosis of infection but few studies describe its utility in real-world settings. We performed a single-center retrospective case series of microbial cell free DNA testing using the Karius assay from 29 patient samples to define the clinical reasoning and the impact of testing. Indications fell into 3 categories, identifying a causative pathogen in patients with an infectious syndrome and negative microbiologic workup (15/29, 52%), seeking another pathogen when organisms identified by traditional diagnostics failed to explain the clinical presentation (9/29, 31%) and to "rule out" infection in patients with nonspecific symptoms and negative microbiologic workup (5/29, 17%). Clinical impact was positive in 13/29 (45%) and all were for patients with high pretest probability for infection. Impact was negative in 3/29 (10%) cases. There was no impact in 15/29 (52%) cases. Further work is needed to define the optimal timing accounting for test performance, and patient characteristics.

Teaching Infectious Disease Pathology and Taking it To Africa.

With the advent of increasing emerging infectious diseases, rising antibiotic resistance, and the growing number of immunocompromised patients, there is increasing demand for infectious disease (ID) pathology expertise and microbiology testing. Currently, ID pathology training and emerging molecular microbiology techniques (eg, metagenomic next-generation sequencing and whole genome sequencing) are not included in the most American Council of Graduate Medical Education medical microbiology fellowship curricula, and not surprisingly, many institutions lack anatomical pathologists with expertise in ID pathology and advanced molecular diagnostics. In this article, we describe the curriculum and structure of the Franz von Lichtenberg Fellowship in Infectious Disease and Molecular Microbiology at Brigham and Women's Hospital in Boston, MA. We emphasize the value of a training model that strives to integrate anatomical pathology, clinical pathology, and molecular pathology by providing examples in a case-based format and presenting selected metrics of the potential effect of such integrative ID pathology service and briefly describing opportunities and challenges of our global health efforts in Rwanda.

Prioritizing Patient Safety and Minimizing Waste: Institutional Review of Cases and a Proposed Process for Designing a Surgical Pathology Gross-Only Examination Policy.

OBJECTIVES: Gross-only examination policies vary widely across pathology departments. Several studies-particularly a College of American Pathologists' Q-Probes study-have looked at the variations in gross-only policies, and even more studies have addressed the (in)appropriateness of certain specimen types for gross-only examination. Few, if any, studies have tackled the important task of how to revise and safely implement a new gross-only examination protocol, especially in collaboration with clinical colleagues. METHODS: We reviewed the grossing protocols from three anatomic pathology centers to identify common gross-only specimen types. We compiled an inclusive list of any specimen types that appeared on one or more centers' lists. We performed a retrospective review of the gross and microscopic diagnoses for those specimen types to determine if any diagnoses of significance would have been missed had that specimen been processed as a gross-only. RESULTS: We reviewed 940 cases among 13 specimen types. For 7 specimen types, the gross diagnoses provided equivalent information to the microscopic diagnoses. For 6 specimen types, microscopic diagnoses provided clinically meaningful information beyond what was captured in the gross diagnoses. CONCLUSIONS: To improve the value of care provided, pathology departments should conduct internal reviews and consider transitioning specimen types to gross-only when safe.

The Effect of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Mitigation Strategies on Seasonal Respiratory Viruses: A Tale of 2 Large Metropolitan Centers in the United States.

To assess the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on seasonal respiratory viruses, absolute case counts and viral reproductive rates from 2019-2020 were compared against previous seasons. Our findings suggest that the public health measures implemented to reduce SARS-CoV-2 transmission significantly reduced the transmission of other respiratory viruses.

Evaluation of the fully automated AIX1000 rapid plasma reagin system compared to a manual plasma reagin testing method for the diagnosis of syphilis.

The analytical performance of the FDA-cleared AIX1000 automated RPR testing platform was evaluated in comparison to manual RPR card testing. Eight hundred thirty-three patient serum samples were analyzed, 87 samples were positive by the AIX1000, 108 were positive by the manual test method; overall agreement between methods was 96.5% (κ = 0.83). Cases were further classified by clinical and laboratory-based confirmation of disease, to which reactivity rates were compared, yielding sensitivities of 96.4% and 100%, and specificities of 99.2% and 96.8% for the automated and manual RPR methods, respectively. The difference in specificity between methods was statistically significant (P < 0.001). Twenty-five of 29 samples with discordant results were reactive by manual testing (titers of 1:1 or 1:2); 21 of 25 patients with negative AIX100 results were identified to have histories of remote, treated syphilis. Overall, the AIX1000 platform demonstrated excellent agreement with the manual RPR method; discrepancies occurred with specimens at the threshold of reactivity.

Epidemiology of carbapenem-resistant Enterobacteriaceae: a 5-year experience at a tertiary care hospital.

PURPOSE: The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing worldwide. Ertapenem resistance is mediated by non-carbapenemase mechanisms, and has less of an effect on susceptibility to imipenem and meropenem. This study aimed to study the epidemiology of CRE, and to compare risk factors and related mortality between non-susceptibility to ertapenem alone Enterobacteriaceae (NSEE), with non-susceptibility to other carbapenems (imipenem, meropenem, or doripenem) Enterobacteriaceae (NSOCE) at a tertiary care hospital in Thailand. METHODS: All CRE isolated were identified between December 2011 and December 2016. Quarterly incidence rate was estimated. Hospital-wide carbapenem consumption was calculated as defined daily doses (DDD). Relationships between hospital-wide carbapenem consumption and incidence of CRE were tested. Factors associated with NSEE and NSOCE, and risk factors associated with 14- and 30-day mortality in patients with CRE infection were determined. RESULTS: The quarterly CRE incidence increased significantly from 3.37 per 100,000 patient-days in the last quarter of 2011 to 32.49 per 100,000 patient-days in the last quarter of 2016. (P for trend <0.001). Quarterly hospital-wide carbapenem consumption increased 1.58 DDD per 1,000 patient-days (P for trend=0.004). The Poisson regression showed the expected increase of CRE incidence was 1.02 per 100,000 patient-days for a 1 DDD per 1,000 patient-days increase in carbapenem consumption (P<0.001). There were 40 patients with NSEE and 134 patients with NSOCE in the 5-year study period. The NSEE group had significantly lower carbapenem exposure compared with the NSOCE group (adjusted odds ratio: 0.25; P=0.001). No difference in 14-day and 30-day all-cause mortality between the two groups was observed. CONCLUSION: The incidence of CRE has risen significantly at our institution. Previous carbapenem use was associated with NSOCE. This hospital-wide carbapenem use was significantly associated with the increasing incidence of CRE.

Inter-pathologist and pathology report agreement for ovarian tumor characteristics in the Nurses' Health Studies.

BACKGROUND: Grade and histotype of ovarian carcinomas are often used as surrogates of molecular subtypes. We examined factors affecting pathologists' reproducibility in two prospective studies. METHODS: Two pathologists independently reviewed slides from 459 incident ovarian cancers in the Nurses' Health Study (NHS) and NHSII. We described agreement on tumor characteristics using percent agreement and Cohen's standard kappa (κ) coefficients. We used logistic regression, with disagreement as the outcome, to evaluate the contribution of case and tumor characteristics to agreement. RESULTS: Inter-rater agreement was 95% (κ = 0.81) for carcinoma versus borderline, 89% (κ = 0.58) for grade and 85% (κ = 0.71) for histotype. Inter-rater grading disagreement was higher for non-serous histotypes (OR = 4.66, 95% CI 2.09-10.36) and lower for cancers with bizarre atypia (OR = 0.13, 95% CI 0.04-0.38). Agreement with original pathology reports was 94% (κ = 0.73) for carcinoma versus borderline, 78% (κ = 0.60) for histotype, and 79% (κ = 0.24) for grade. Grading disagreement was significantly lower for tumors with 'solid, pseudoendometrioid or transitional' (SET) architecture (OR = 0.08, 95%CI 0.01-0.84). Date of original diagnosis, hospital type, number of slides available for review, tumor stage, and slide quality were not related to agreement. CONCLUSION: Overall, inter-rater agreement for tumor type and grade for archival tissue specimens was good. Agreement between the consensus review and original pathology reports was lower. Factors contributing to grading disagreement included non-serous histotype, absence of bizarre atypia, and absence of SET architecture.

Synovial sarcoma presenting as a lung mass and diagnosed by cytology.

Synovial sarcoma is a common soft tissue sarcoma with variable fibrous and epithelial differentiation that rarely arises from other body sites, such as within the lung. A case of a 68-year-old male with an extensive smoking history who presented with chest pain and a primary, central, metabolically active lung mass was reported. The mass was biopsied by bronchial brushing, bronchoalveolar lavage (BAL), and transbronchial fine-needle aspiration (FNA). Cytologic analysis of bronchial brushing, BAL, and FNA revealed single and clusters of atypical spindle cells, oval, or spindle-shaped nuclei with smooth nuclear membranes, hyperchromatic and granular chromatin, scant to moderate and delicate cytoplasm, a high degree of mitotic figures, and a lack of necrosis. Immunohistochemical studies showed that the tumor cells were positive for CD99, BCL2, and CK7. A diagnosis of synovial sarcoma was rendered. The differential diagnosis of primary pulmonary synovial sarcoma is discussed, including neuroendocrine tumors, squamous cell carcinoma, and various sarcomatous tumors.