Laboratory approaches to determining blood culture contamination rates: an ASM Laboratory Practices Subcommittee report.

Blood culture contamination (BCC) is the presence of specific commensal and environmental organisms cultivated from a single blood culture set out of a blood culture series and that do not represent true bacteremia. BCC can impact quality of care and lead to negative outcomes, unnecessary antibiotic exposure, prolonged hospital stays, and substantial costs. As part of the laboratory's quality management plan, microbiology laboratory personnel are tasked with monitoring BCC rates, preparing BCC rate reports, and providing feedback to the appropriate committees within their healthcare system. The BCC rate is calculated by the laboratory using pre-set criteria. However, pre-set criteria are not universally defined and depend on the individual institution's patient population and practices. This mini-review provides practical recommendations on elaborating BCC rate reports, the parameters to define for the pre-set criteria, how to collect and interpret the data, and additional analysis to include in a BCC report.

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.

In Vitro Activity of Omadacycline and Comparator Antibiotics against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Urinary Isolates.

Limited oral antibiotic options exist for urinary tract infections (UTI) caused by ESBL-producing Enterobacterales. The aim of the study was to evaluate in vitro activity of omadacycline and comparator antibiotics against clinical ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae urinary isolates. 102 isolates each of E. coli and K. pneumoniae were collected from clinical urine specimens in 2019. By design, an equal number of each species were included that tested positive and negative for ESBL production. Omadacycline MICs were determined using gradient test strips and compared to MICs of comparator antibiotics as determined by an automated broth microdilution system. Isolates were considered susceptible to omadacycline if the MIC was ≤4 µg/mL for each species. 54.9% of all ESBL-producing isolates were susceptible to omadacycline, but better susceptibility was observed for ESBL-producing E. coli (74.5%). Omadacycline MICs were 2-4 fold lower for E. coli and K. pneumoniae strains not producing ESBL. The omadacycline MIC 50 and 90 values were 4 and 16 µg/mL, respectively, for all isolates studied. 74.5% of all isolates were considered susceptible to omadacycline. MICs were generally lower for E. coli strains with MIC 50 and 90 values of 4 and 8 µg/mL, respectively (87.3% susceptible), compared with K. pneumoniae. Overall, the most active agents were omadacycline and nitrofurantoin, while other comparator antibiotics were less active. Omadacycline represents a promising oral antibiotic for treating UTI caused by ESBL-producing E. coli, particularly when resistance limits other oral options. Prospective, controlled clinical trials are needed to validate these in vitro results.

Rare, Atypical Mycobacterium Infection of the Hand in Immunocompetent Individuals.

We present two cases of immunocompetent individuals diagnosed with nontuberculous infections of the hand caused by organisms rarely seen in the clinical setting: Mycobacterium heckeshornense and Mycobacterium chelonae. In the first case, a 50-year-old male presented with tenosynovitis of left long finger. He was subsequently found to have a Mycobacterium heckeshornense infection that was resolved with multiple surgeries and a long-term regimen of several antibiotics. The second case was a 29-year-old female with a history of a trivial hand injury infected with Mycobacterium chelonae. She was successfully treated with surgical debridement and antibiotics over the course of eight months. It is important to recognize the increasing prevalence of these two species of bacteria as human pathogens that can result in infections of the extremities even in immunocompetent individuals. (Journal of Surgical Orthopaedic Advances 32(1):055-058, 2023).

Analysis of infections among patients with historical culture positive for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae: Is ESBL-targeted therapy always needed?

Objective: Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions. Methods: A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP. Results: In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3. Conclusions: History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

Clinical impact of a multiplex rapid diagnostic pneumonia panel in critically ill patients.

Objective: To evaluate the clinical impact of the BioFire FilmArray Pneumonia Panel (PNA panel) in critically ill patients. Design: Single-center, preintervention and postintervention retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Adult ICU patients. Methods: Patients with quantitative bacterial cultures obtained by bronchoalveolar lavage or tracheal aspirate either before (January-March 2021, preintervention period) or after (January-March 2022, postintervention period) implementation of the PNA panel were randomly screened until 25 patients per study month (75 in each cohort) who met the study criteria were included. Antibiotic use from the day of culture collection through day 5 was compared. Results: The primary outcome of median time to first antibiotic change based on microbiologic data was 50 hours before the intervention versus 21 hours after the intervention (P = .0006). Also, 56 postintervention regimens (75%) were eligible for change based on PNA panel results; actual change occurred in 30 regimens (54%). Median antibiotic days of therapy (DOTs) were 8 before the intervention versus 6 after the intervention (P = .07). For the patients with antibiotic changes made based on PNA panel results, the median time to first antibiotic change was 10 hours. For patients who were initially on inadequate therapy, time to adequate therapy was 67 hours before the intervention versus 37 hours after the intervention (P = .27). Conclusions: The PNA panel was associated with decreased time to first antibiotic change and fewer antibiotic DOTs. Its impact may have been larger if a higher percentage of potential antibiotic changes had been implemented. The PNA panel is a promising tool to enhance antibiotic stewardship.

Analytical evaluation of the cobas® 6800 system for the detection and quantification of BK Virus (BKV) and Epstein Barr Virus (EBV) at a US solid organ and hematopoietic stem cell transplant center.

The cobas® EBV and BKV assays are the first FDA-approved, quantitative assays for monitoring posttransplant reactivation of these viruses. In this study, we assessed performance of the fully-automated cobas® assays, compared with Diasorin Molecular ASR, our laboratory developed test, and demonstrated a strong interassay correlation for BK and EBV monitoring.

A comparison of active versus passive methods of responding to rapid diagnostic blood culture results.

Objective: To compare 2 methods of communicating polymerase chain reaction (PCR) blood-culture results: active approach utilizing on-call personnel versus passive approach utilizing notifications in the electronic health record (EHR). Design: Retrospective observational study. Setting: A tertiary-care academic medical center. Patients: Adult patients hospitalized with ≥1 positive blood culture containing a gram-positive organism identified by PCR between October 2014 and January 2018. Methods: The standard protocol for reporting PCR results at baseline included a laboratory technician calling the patient's nurse, who would report the critical result to the medical provider. The active intervention group consisted of an on-call pager system utilizing trained pharmacy residents, whereas the passive intervention group combined standard protocol with real-time in-basket notifications to pharmacists in the EHR. Results: Of 209 patients, 105, 61, and 43 patients were in the control, active, and passive groups, respectively. Median time to optimal therapy was shorter in the active group compared to the passive group and control (23.4 hours vs 42.2 hours vs 45.9 hours, respectively; P = .028). De-escalation occurred 12 hours sooner in the active group. In the contaminant group, empiric antibiotics were discontinued faster in the active group (0 hours) than in the control group and the passive group (17.7 vs 7.2 hours; P = .007). Time to active therapy and days of therapy were similar. Conclusions: A passive, electronic method of reporting PCR results to pharmacists was not as effective in optimizing stewardship metrics as an active, real-time method utilizing pharmacy residents. Further studies are needed to determine the optimal method of communicating time-sensitive information.

Storage Artifact Masquerading as Yeast: Presenting a Diagnostic Pitfall.

Abnormal cell morphology can result from prolonged specimen storage, both for red and white blood cells. In particular, nuclear pyknosis of segmented neutrophils can occur in both peripheral blood and body fluids and may represent a diagnostic pitfall as it can mimic intracellular yeast or bacteria morphology. Pathologists are frequently asked to examine body fluid smears which are thought to contain microorganisms, and the presence of an unexpected organism can be especially concerning. Morphologic changes from prolonged storage may be encountered infrequently, and it is important to be aware of them in order to avoid misrepresentation, as additional work-up may be required for a suspected case of an unexpected fungal infection.

Evaluation of the Potential Impact of a Multiplex Rapid Diagnostic Panel in Critically Ill Patients With Hospital-Acquired Pneumonia.

Background Rapid diagnostic tools have emerged as valuable assets assisting clinicians in decision-making regarding patient management in the hospital setting. Our study sought to identify the potential impact of the BioFire® FilmArray® Pneumonia Panel (FP Panel) (BioFire Diagnostics, Salt Lake City, UT, USA) in patients with hospital-acquired pneumonia (HAP). Methods Respiratory samples obtained by bronchoalveolar lavage (BAL) or tracheal aspiration (TA) from ICU patients with a diagnosis of HAP were tested by the FP panel in addition to routine bacterial cultures. In addition, the electronic health records of these patients were reviewed to determine what potential changes in antimicrobial therapy could have been implemented if the panel results were known to the treatment team in real-time. A cost analysis was also performed incorporating the cost of the pneumonia panel and the savings associated with the potential decrease of antibiotic use and avoidance of the rapid viral diagnostic panel.  Results Fifty-six patients met the study criteria. The FP panel results could have prompted a change in therapy in 36 (64.3%) patients, with an anticipated mean reduction in time to optimized therapy of approximately 51 hours. In addition, the panel identified three cases where antimicrobials should have been altered because patients were not receiving empiric therapy with activity against the causative pathogen and 34 opportunities for antibiotic de-escalation. The cost analysis calculated an additional cost of $10 per patient associated with using the FP panel.  Conclusions The FP panel could have prompted a change in therapy in about two-thirds of patients studied. Its potential benefits include a more rapid time to optimized therapy, reduced exposure to and cost of broad-spectrum antimicrobials, and reduced cost of other rapid diagnostic tests.

High Number of Positive Rapid Plasma Reagin With Low Titers Using the Automated AIX 1000 RPR System.

ABSTRACT: This study evaluated the performance of manual rapid plasma reagin (RPR) and automated AIX1000 RPR tests for the diagnosis of syphilis. Manual RPR showed a 3% reactive result compared with 5.8% for the automated test mainly because of RPR reactive results with low titers not confirmed by Treponema pallidum particle agglutination.

Impact of the AACC Global Laboratory Quality Initiative in Partnership with Professional Societies and Universities in Latin America and the Caribbean.

The Global Lab Quality Initiative (GLQI), formerly known as the Emerging Countries program, was funded through a generous endowment from the Wallace H. Coulter Foundation. The aims of GLQI are to develop and implement innovative programs to promote education and training in laboratory medicine for low- or lower middle-income countries worldwide. From its inception in 2010, the GLQI was focused solely on the Latin America and Caribbean (LAC) region under the purview of AACC's Latin American Working Group (LAWG), the members of which have strong ties to the region thereby facilitating the partnerships with national societies. The LAWG has provided in-person workshops in the LAC countries, at the AACC Annual Scientific Meeting, and on-demand webinars. The LAWG aims to implement the GLQI aims in the LAC region. In-person workshops are based on best-practice recommendations and sources such as Clinical Laboratory Standard Institute guidelines and supplemented with professional experiences of the LAWG's lecturers and local experts of the countries visited. In 2015, the GLQI expanded to other regions of the world. Here we report the experience of the LAWG workshops, results of participant surveys, in-person visits to laboratories post-workshop, and the lessons learned throughout the years across different geographic areas. We are hopeful this report provides insights into the challenges and successes of the LAWG in LAC to help support the expansion of the GLQI.

Treatment of Candida nivariensis Blood Stream Infection With Oral Isavuconazole.

Candida nivariensis is a rarely isolated yeast that is now considered a species within the Candida glabrata complex. Anti-fungal susceptibilities and treatments of Candida nivariensis are often assessed on a case-by-case basis. In this case, a 70-year-old male with a complex medical history presented to a large academic medical center in the United States for vascular surgery. After surgery, the patient's white blood cell count increased prompting an infectious workup. The patient was found to have a Candida nivariensis bloodstream infection of unknown origin. Given the patient's clinical stability and QTc prolongation, he was treated with a 14-day course of oral isavuconazole. The patient experienced resolution of symptoms and clearance of subsequent blood cultures. At the time of writing this case report (11 months later), he has had no relapse of his fungal infection. Based on a search of the medical literature, this appears to be the first published case of Candida nivariensis fungemia successfully treated with oral isavuconazole.

A case report of Nocardia spp. infective endocarditis in an injection drug user.

BACKGROUND: Nocardia-related endocarditis is rare. Intravenous drug use with nonsterile injection practices is a potential risk factor for nocardia infection. Disseminated nocardiosis with endovascular involvement is rarely reported in immunocompetent individuals. CASE PRESENTATION: A 54-year-old male was diagnosed with infective endocarditis due to Nocardia asteroides with septic emboli in the brain and spleen. The use of a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) rapid diagnostic system was beneficial in identifying the causative organism. He was empirically treated with combination therapy consisting of three antibiotics. Antimicrobial susceptibility testing indicated that all three antibiotics had favorable minimum inhibitory concentrations (MICs). Due to his clinical status, he was not a surgical candidate. Patient passed away after discharge to hospice. CONCLUSIONS: This case demonstrates unique challenges in the identification, diagnosis, and management of Nocardia-related infective endocarditis. A detailed history of injection practices should guide clinicians in assessing the risk for environmental pathogens. Valvular surgery and combination antibiotic therapy should be recommended for all eligible patients to improve the chances of survival.

Implementation and Evaluation of Gradient Strip Antimicrobial Susceptibility Testing in US Public Health Laboratories to Respond to Resistant Gonorrhea.

BACKGROUND: Gradient strip antimicrobial susceptibility testing using Etest is conducted by local public health jurisdictions participating in the Strengthening the US Response to Resistant Gonorrhea (SURRG) program to inform public health responses to resistant gonorrhea. Proficiency testing results across the participating laboratories were analyzed and a comparison of Etest with the agar dilution method was conducted. METHODS: Laboratories participating in SURRG performed Etest for azithromycin (AZM), cefixime (CFX), and ceftriaxone (CRO). Concurrence between minimum inhibitory concentrations (MICs) obtained with Etest versus the agar dilution method using corresponding isolates was defined as ±1 double dilution. Specific levels of reduced susceptibility were termed "alerts" and included isolates with the following MICs: ≥2.0 µg/mL (AZM), ≥0.25 µg/mL (CFX), and ≥0.125 µg/mL (CRO). Categorical (alert/nonalert) agreement was calculated for MICs determined using Etest and agar dilution methods. RESULTS: Strengthening the US Response to Resistant Gonorrhea laboratories had high proficiency testing scores (≥98%) and low levels of interlaboratory variations in MICs. The overall concurrence of MICs (essential agreement) determined using agar dilution, and Etest was 96% (CRO), 96% (CFX), and 95% (AZM). Depending on the antibiotic tested, between 27% and 66% of isolates with alert MICs determined by Etest also had alert MICs using the reference agar dilution methodology; however, most of these alert MICs were detected at threshold levels. CONCLUSIONS: This study demonstrates that MICs produced by SURRG laboratories using Etest have a high level of concurrence with agar dilution. Although confirmation of specific alert MICs varied, Etest facilities rapid detection and response to emerging resistant gonorrhea.

A two-transcript biomarker of host classifier genes for discrimination of bacterial from viral infection in acute febrile illness: a multicentre discovery and validation study.

BACKGROUND: Acute febrile illness is one of the main reasons for outpatient hospital visits worldwide. However, differential diagnosis between bacterial and viral causes is challenging and misdiagnosis can result in antimicrobial overuse and hinder prompt treatment. We aimed to build and validate a diagnostic model to discriminate bacterial from viral infection in acute febrile illness by evaluating the expression of potential classifier host genes. METHODS: In this multicentre discovery and validation study, we included patients aged 14-85 years with acute febrile illness (fever for ≤14 days, axillary temperature of ≥38°C, and confirmed bacterial infection, viral infection, or non-infectious inflammatory disease), and healthy control participants (no significant medical history and no fever within the past 90 days) from four hospitals in Shandong province, China. Patients from the first hospital were divided into the screening, discovery, and internal validation groups, and patients from the three other hospitals comprised the external validation group. We measured expression of candidate genes in peripheral blood by RT-PCR, and patients for whom a successful RT-PCT result was recorded were included in the next-step analysis. For patients from the first hospital, those enrolled during the early phase of the study were assigned to the screening group, which was used to identify the optimal transcripts (IFI44L and PI3) for discrimination between bacterial and viral infections by screening four candidate genes (FAM89A, IFI44L, PI3, and ITGB2) by RT-PCR. The remaining patients were then randomly assigned (1:1) to discovery and internal validation groups by time of admission and blood drawing via the equidistant random sampling method. A logistic regression model integrating the mRNA levels of IFI44L and PI3 was built by use of the discovery group, and the diagnostic performance of the model was evaluated in the internal and external validation groups using area under the receiver operating curve (AUC), sensitivity, and specificity. FINDINGS: Between March 1, 2018, and Aug 31, 2019, we assessed 1658 individuals for inclusion in the study. After exclusion of ineligible participants, 458 participants were enrolled (178 patients with acute febrile illness caused by bacterial infection, 212 with acute febrile illness caused by viral infection, 38 with non-infectious inflammatory diseases, and 30 healthy controls). The 390 patients with bacterial or viral infections were assigned to one of four groups: screening (n=64, 33 with bacterial infections and 31 with viral infections), discovery (n=124, 55 with bacterial infections and 69 with viral infections), internal validation (n=124, 55 with bacterial infections and 69 with viral infections), and external validation (n=78, 35 with bacterial infections and 43 with viral infections). Of the four candidate host genes (FAM89A, IFI44L, PI3, and ITGB2), IFI44L and PI3 showed the most discriminative expression pattern and were used to build the logistic regression model. We established the optimal cutoff of the bacterial infection likelihood score to be 0·547598. With the diagnostic result from the gold standard tests (culture and PCR) as the reference, the two-transcript classifier model had an AUC of 0·969 (95% CI 0·937-1·000), sensitivity of 0·891 (0·782-0·949), and specificity of 0·971 (0·900-0·992) to discriminate bacterial and viral infections in the internal validation group. The model showed similar results in the external validation group (AUC 0·986, 95% CI 0·968-1·000; sensitivity 0·857, 0·706-0·937; and specificity 0·954, 0·845-0·987). INTERPRETATION: IFI44L and PI3 transcripts, measured by RT-PCR, are robust classifiers to discriminate bacterial from viral infection in acute febrile illness. This two-transcript biomarker has the potential to be transformed into a commercial panel and applied universally. FUNDING: None.