Defining the value of medical microbiology consultation.

Medical microbiologists, defined as doctoral-level laboratory directors with subspecialty training in medical microbiology, lead the clinical laboratory operations through activities such as clinical consultations, oversight of diagnostic testing menu, institutional leadership, education, and scholastic activities. However, unlike their clinical colleagues, medical microbiologists are largely unable to bill for clinical consultations performed within the hospital and, therefore, unable to generate relative value units or a similar quantifiable metric. As hospital budgets tighten and justification of staffing becomes a necessity, this may present a challenge to the medical microbiologist attempting to prove their value to the organization. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. Consults were generated equally from internal (laboratory-based) and external (hospital-based) parties, with the majority directly impacting patient management. Near universal acceptance of the medical microbiologist's recommendation highlights the worth derived from their expertise. External consults required more time commitment from the medical microbiologist than internal consults, although both presented ample opportunity for secondary value, including impact through stewardship, education, clinical guidance, and cost reduction. This study is a description of the content and impact of consultations that underscore the importance of the medical microbiologist as a key member of the healthcare team. IMPORTANCE: Medical microbiologists are invaluable to the clinical microbiology laboratory and the healthcare system as a whole. However, as medical microbiologists do not regularly generate relative value units, capturing and quantifying the value provided is challenging. As hospital budgets tighten, justification of staffing becomes a necessity. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. To our knowledge, this is the first study to provide detailed evaluation of the consultative value provided by medical microbiologists.

A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC.

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.

Point-of-Care Testing for the Diagnosis of Fungal Infections: Current Testing Applications and Potential for the Future.

Invasive fungal infections are increasing worldwide due to factors such as climate change and immunomodulating therapies. Unfortunately, the detection of these infections is limited due to the low sensitivity and long periods required for laboratory testing. Point-of-care testing could lead to more rapid diagnosis of these often devasting infections. However, there are currently no true point-of-care tests on the market for the detection of fungi. In this article, the current state of fungal antigen and molecular testing is reviewed, with commentary on the potential for development and use in the point-of-care setting.

Early initiation of three-drug combinations for the treatment of carbapenem-resistant A. baumannii among COVID-19 patients.

OBJECTIVES: We evaluated the clinical characteristics and outcomes of patients with COVID-19 who received three-drug combination regimens for treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections during a single-centre outbreak. Our objective was to describe the clinical outcomes and molecular characteristics and in vitro synergy of antibiotics against CRAB isolates. MATERIALS AND METHODS: Patients with severe COVID-19 admitted between April and July 2020 with CRAB infections were retrospectively evaluated. Clinical success was defined as resolution of signs/symptoms of infection without need for additional antibiotics. Representative isolates underwent whole-genome sequencing (WGS) and in vitro synergy of two- or three-drug combinations was assessed by checkerboard and time-kill assays, respectively. RESULTS: Eighteen patients with CRAB pneumonia or bacteraemia were included. Treatment regimens included high-dose ampicillin-sulbactam, meropenem, plus polymyxin B (SUL/MEM/PMB; 72%), SUL/PMB plus minocycline (MIN; 17%) or other combinations (12%). Clinical resolution was achieved in 50% of patients and 30-day mortality was 22% (4/18). Seven patients had recurrent infections, during which further antimicrobial resistance to SUL or PMB was not evident. PMB/SUL was the most active two-drug combination by checkerboard. Paired isolates collected before and after treatment with SUL/MEM/PMB did not demonstrate new gene mutations or differences in the activity of two- or three-drug combinations. CONCLUSIONS: Use of three-drug regimens for severe CRAB infections among COVID-19 resulted in high rates of clinical response and low mortality relative to previous studies. The emergence of further antibiotic resistance was not detected phenotypically or through WGS analysis. Additional studies are needed to elucidate preferred antibiotic combinations linked to the molecular characteristics of infecting strains.

Comparative Evaluation of Current Biochemical-, Sequencing-, and Proteomic-Based Identification Methods for the Streptococcus bovis Group.

The Streptococcus bovis group (previously group D streptococci) consists of seven distinct species and subspecies. Definitive identification within the group is important, as certain organisms have been associated with gastrointestinal carcinoma, bacteremia, infective endocarditis, meningitis, biliary tract disease, and carcinoma, among others. Definitive identification, however, remains elusive due to limitations and inconsistencies across commonly used identification platforms in the United States. Here, we compared the performance of standard biochemical (Trek Gram-positive identification [GPID] plate, Vitek 2 GPID), sequencing (16S rDNA, sodA) databases (NCBI, RDP, CDC MicrobeNet), and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) platforms (Vitek MS, Bruker Biotyper MS) using a set of eight type strains representing all seven strains within the S. bovis group. Despite the evaluation of contemporary methods, no single platform was able to definitively identify all type strains within the S. bovis group. Vitek MS (85.7%, 7/8) provided the most accurate definitive identifications, followed by sodA sequencing (75%, 6/8). Vitek 2 and Bruker Biotyper RUO platforms performed the next best (62.5%, 5/8). All remaining platforms failed to adequately differentiate type strains within the S. bovis group (range, 0 to 37.5%). Laboratorians and clinicians should be aware of the identification limitations of routine testing algorithms and incorporate reflex testing, when appropriate, to platforms such as Vitek MS and/or sodA sequencing that are more able to definitively identify S. bovis group organisms. Further clinical evaluation was conducted using 65 clinical isolates from three geographically distinct U.S. institutions. Future improvements in identification platforms may reveal new clinical and epidemiological trends for members of the S. bovis group.

Severe Infective Endocarditis Caused by Bartonella rochalimae.

A 22-year-old man from Guatemala sought care for subacute endocarditis and mycotic brain aneurysm after living in good health in the United States for 15 months. Bartonella rochalimae, a recently described human and canine pathogen, was identified by plasma microbial cell-free DNA testing. The source of infection is unknown.

Overprediction of Carbapenemase-Containing Isolates by an Automated AST Instrument's Computer Algorithm.

BACKGROUND: The VITEK® 2 is generally accepted as a reliable method for predicting antibiotic resistance mechanisms including aminoglycoside phenotypes, beta lactam phenotypes, impermeability, and penicillinases. However, when it comes to predicting carbapenemases, the research that has been done is inconsistent in both methods and results. METHODS: We compared the predictions of the VITEK 2 and Advanced Expert System™ (AES) with the results of the modified carbapenemase inactivation method in an academic medical center lab to evaluate the clinical reliability of the VITEK 2 and AES in routine workflow for the detection of carbapenemases. RESULTS: Our findings show that the positive predictive value of carbapenemase detection on the VITEK2 and AES is 30.3% (91/300) in our patient population. CONCLUSIONS: In light of these results, we propose that the VITEK 2 and AES be used as a screening tool for carbapenemase-containing organisms rather than as a definitive test.

Clinical utility of antifungal susceptibility testing.

Invasive fungal diseases cause significant morbidity and mortality, in particular affecting immunocompromised patients. Resistant organisms are of increasing importance, yet there are many notable differences in the ability to both perform and interpret antifungal susceptibility testing compared with bacteria. In this review, we will highlight the strengths and limitations of resistance data of pathogenic yeasts and moulds that may be used to guide treatment and predict clinical outcomes.

Clinical impact of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decisions: a single-center retrospective study.

BACKGROUND: Metagenomic next-generation sequencing of microbial cell-free DNA (mcfDNA) allows for non-invasive pathogen detection from plasma. However, there is little data describing the optimal role for this assay in real-world clinical decision making. METHODS: We performed a single-center retrospective cohort study of adult patients for whom a mcfDNA (Karius©) test was sent between May 2019 and February 2021. Clinical impact was arbitrated after review and discussion of each case. RESULTS: A total of 80 patients were included. The most common reason for sending the assay was unknown microbiologic diagnosis (78%), followed by avoiding invasive procedures (14%). The test had a positive impact in 34 (43%), a negative impact in 2 (3%), and uncertain or no impact in 44 (55%). A positive impact was observed in solid organ transplant recipients (SOTR, 71.4%, p = 0.003), sepsis (71.4%, p = 0.003), and those receiving antimicrobial agents for less than 7 days prior to mcfDNA testing (i.e., 61.8%, p = 0.004). Positive impact was driven primarily by de-escalation of antimicrobial therapy. CONCLUSION: Clinical impact of mcfDNA testing was highest in SOTR, patients with sepsis and patients who had been on antimicrobial therapy for less than 7 days. Positive impact was driven by de-escalation of antimicrobial therapy which may highlight a potential role for mcfDNA in the realm of stewardship.

Wohlfahrtiimonas chitiniclastica Monomicrobial Bacteremia in a Homeless Man.

We report a case of septic shock attributable to monomicrobial bloodstream infection secondary to Wohlfahrtiimonas chitiniclastica infection. This case suggests that W. chitiniclastica likely possesses the virulence to cause severe disease. Culture-independent techniques were essential in the identification of this organism, which enabled selection of appropriate therapy.

Streptococcus pyogenes Infective Endocarditis-Association With Injection Drug Use: Case Series and Review of the Literature.

BACKGROUND: Streptococcus pyogenes, or Group A Streptococcus (GAS), is not considered a typical cause of infective endocarditis (IE), but has anecdotally been observed in unexpectedly high rates in people who inject drugs (PWID) at our institution. METHODS: All cases of possible or definite GAS IE per Modified Duke Criteria in adults at an academic hospital between 11/15/2015 and 11/15/2020 were identified. Medical records were reviewed for demographics, comorbidities, treatment, and outcomes related to GAS IE. The literature on cases of GAS IE was reviewed. RESULTS: Eighteen cases of probable (11) or definite (7) GAS IE were identified; the mean age was 38 years, and the population was predominantly female (56%) and Caucasian (67%), which is inconsistent with local population demographics. Sixteen cases were in people who inject drugs (PWID; 89%); 14 were also homeless, 6 also had HIV (33%), and 2 were also pregnant. Antibiotic regimens were variable due to polymicrobial bacteremia (39%). One patient underwent surgical valve replacement. Four patients (22%) died due to complications of infection. The literature review revealed 42 adult cases of GAS IE, only 17 of which were in PWID (24%). CONCLUSIONS: The 16 cases of possible and definite GAS IE in PWID over a 5-year period in a single institution reported nearly doubles the number of cases in PWID from all previous reports. This suggests a potential increase in GAS IE particularly in PWID and PWH, which warrants further epidemiologic investigation.

Comparison of Three Sample-to-Answer RT-PCR Testing Platforms for the Detection of SARS-CoV-2 RNA in Positive Nasopharyngeal and Nasal Swabs.

BACKGROUND: The COVID-19 pandemic has strained clinical microbiology laboratories due to testing supply allocations. As a result, laboratories have had to invest in multiple COVID-19 assays performed on different testing instruments. Comparing the results achieved by testing positive samples between in-use assays can provide insights into which platforms may be interchangeable for testing in times of supply chain emergencies. METHODS: Nasopharyngeal and nasal swab specimens collected in viral transport media that tested positive on the Xpert® Xpress SARS-CoV-2 assay were tested on the ePlex® SARS-CoV-2 and BD SARS-CoV-2 Reagents for BD Max™ assays. Positive percent agreement was calculated using the Xpert Xpress SARS-CoV-2 assay as the reference method. RESULTS: We tested 78 positive swabs, resulting in a positive percentage agreement (PPA) of 92% (CI 84-97%) for the BD SARS-CoV-2 assay and 58% (CI 47-70%) for the ePlex assay. Following development of a new workflow for the ePlex, we detected SARS-CoV-2 in 7 additional samples, resulting in a new PPA of 68% (CI 56-78). CONCLUSIONS: During times of supply allocation and shortage of the Xpert Xpress SARS-CoV-2 assay, the BD SARS-CoV-2 assay is well suited to test substitutions due to its high PPA.

Evaluation of Inappropriate COVID-19 RT-PCR Test Utilization at an Academic Medical Center.

BACKGROUND: An evolving COVID-19 testing landscape and issues with test supply allocation, especially in the current pandemic, has made it challenging for ordering providers. We audited orders of the Xpert® Xpress SARS-CoV-2 PCR with reverse transcription (RT-PCR) platform-the fastest of several other testing modalities available-to illuminate these challenges utilizing a multidisciplinary laboratory professional team consisting of a pathology resident and microbiology laboratory director. METHODS: Retrospective review of the first 5 hundred Xpert Xpress SARS-CoV-2 RT-PCR test orders from a 2-week period to determine test appropriateness based on the following indications: emergency surgery, emergent obstetric procedures, initial behavioral health admission, and later including discharge to skilled care facilities and pediatric admissions. Our hypothesis was that a significant proportion of orders for this testing platform were inappropriate. RESULTS: On review, a significant proportion of orders were incorrect, with 69.8% (n = 349, P < 0.0001) not meeting indications for rapid testing. Of all orders, 249 designated as emergency surgery were inappropriate, with 49.0% of those orders never proceeding with any surgical intervention; most of these were trauma related (64.6% were orders associated with a trauma unit). CONCLUSIONS: Significant, pervasive inappropriate ordering practices were identified at this center. A laboratory professional team can be key to identifying problems in testing and play a significant role in combating inappropriate test utilization.

Blood usage at a large academic center in Maryland in relation to the COVID-19 pandemic in 2020.

BACKGROUND: Blood usage and collections were impacted throughout 2020 both by the severity of the COVID-19 pandemic as well as public health decisions affecting hospital operations. We sought to understand the longer-term effects of the pandemic on blood usage via changes in case volume and clinical intensity as well as whether the blood needs of COVID-19-positive patients differed from other transfused patients. STUDY DESIGN AND METHODS: A single-center retrospective study of blood use in 2020 as compared to 2014-2019 was conducted at a tertiary care center. Statistical analysis was performed in an R-based workflow. p values are reported using two-sided t-tests for total hospital blood usage and using Mann-Whitney U tests for comparisons of patient blood usage. RESULTS: Mean monthly red cell usage in 2020 decreased by 11.2% (p = .003), plasma usage decreased by 23.8%, (p < .001) platelet usage decreased by 11.4% (p < .001), and monthly cryoprecipitate use increased by 18% (p = .03). A linear regression model predicted significant associations between total blood usage and the year, number of Medicare eligible discharges, and Case Mix Index. COVID-19-positive patients requiring at least one blood product did not use significantly different amounts of red cells, plasma, or platelets from all other transfused patients. CONCLUSIONS: Year 2020 began with decreased blood usage that was normalized by late spring. Reassuringly, transfused COVID-19-positive patients in general and those requiring ICU level care do not use significantly increased amounts of blood as compared to similar transfused hospital patients.

Rapid Spread and Control of Multidrug-Resistant Gram-Negative Bacteria in COVID-19 Patient Care Units.

We describe rapid spread of multidrug-resistant gram-negative bacteria among patients in dedicated coronavirus disease care units in a hospital in Maryland, USA, during May-June 2020. Critical illness, high antibiotic use, double occupancy of single rooms, and modified infection prevention practices were key contributing factors. Surveillance culturing aided in outbreak recognition and control.

Recognition of Diagnostic Gaps for Laboratory Diagnosis of Fungal Diseases: Expert Opinion from the Fungal Diagnostics Laboratories Consortium (FDLC).

Fungal infections are a rising threat to our immunocompromised patient population, as well as other nonimmunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens; and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.

Multicenter retrospective cohort study of the clinical significance of Staphylococcus lugdunensis isolated from a single blood culture set.

BACKGROUND: Staphylococcus lugdunensis is a coagulase negative Staphylococcus species and frequent human skin commensal with the potential for aggressive infection. Guidance surrounding S. lugdunensis bacteremia (SLB) from a single set of blood cultures is lacking. METHODS: A multicenter, retrospective cohort of patients with SLB from at least one blood culture set within the University of Maryland Medical System from 2015 to 2019 is presented. Objectives are to describe baseline characteristics, compare the clinical status and treatment course, and to evaluate the clinical outcomes among patients with SLB in single versus multiple sets. RESULTS: Thirty-six patients were included, 24 with one set of blood cultures positive for S lugdunensis and 12 with multiple sets. Baseline characteristics were similar between the groups, though patients with SLB in multiple sets were more commonly on hemodialysis (P = 0.029). Central lines were the most common source (17%). Most (97%) fulfilled systemic inflammatory response syndrome or Souvenir criteria, had an infectious focus on imaging, or had a second positive culture site. Most (78%) were treated as clinically significant. Patients with multiple positive sets were more commonly treated with antibiotics for >2 weeks (P = 0.02). CONCLUSIONS: SLB was rare and occurred more frequently as a single set of positive cultures. Patient characteristics and clinical courses were similar between single and multiple set groups. Given the potential severity of S. lugdunensis bacteremia it seems prudent to treat S. lugdunensis in a single blood culture as true bacteremia, pending larger studies and guidelines.