Clinical microbiology informatics.

The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future.

The index case for the fungal meningitis outbreak in the United States.

Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.

High Prevalence of Multistep Algorithms in Diagnostic Clostridioides difficile Laboratory Testing.

CONTEXT.­: Laboratory testing practices for diagnosis of Clostridioides difficile infection (CDI) have evolved in response to published guidelines, availability of highly sensitive nucleic acid amplification tests (NAATs), perceived problems with the specificity of NAATs, and CDI reporting requirements. OBJECTIVE.­: To assess the current state of laboratory practice for diagnostic CDI testing. DESIGN.­: An optional 8-item supplemental questionnaire was distributed in December 2019 to the 1374 laboratories participating in the College of American Pathologists C difficile Detection (CDF) proficiency testing program challenge CDF-C. RESULTS.­: Of 1374 CDF-C participants, 1160 (84.4%) responded, predominantly representing laboratories based in the United States (1077 of 1160; 92.8%). The majority reported using a multistep testing algorithm (684 of 1159; 59.0%). Initial testing with a glutamate dehydrogenase and toxin A/B combination test followed by NAAT for discrepant results was the most common testing method (360 of 1146; 31.4%). NAAT alone (299 of 1146; 26.1%) was next, then NAAT followed by an assay that included toxin A/B enzyme immunoassay if NAAT is positive (258 of 1146; 22.5%). Only 5.4% (62 of 1146) reported using toxin A/B immunoassay alone. Most respondents (1093 of 1131; 96.6%) reported rejecting CDI tests on formed stool, but rejection of CDI testing in pediatric patients was uncommon (211 of 1131; 18.7%). Rejection of CDI testing in patients using laxatives was reported more often by US-based respondents (379 of 1054 [36.0%] versus 9 of 77 [11.7%], P < .001). CONCLUSIONS.­: Multistep algorithms for CDI diagnosis are widely used in line with published recommendations. Most respondents reported rejection of formed stool for CDI testing, but few reported rejection of testing in infants and patients taking laxatives, suggesting these may be areas of opportunity for laboratories to pursue in improving CDI testing practices.

Raising the Bar: Improving Antimicrobial Resistance Detection by Clinical Laboratories by Ensuring Use of Current Breakpoints.

BACKGROUND: Antimicrobial resistance (AMR) is a pressing global challenge detected by antimicrobial susceptibility testing (AST) performed by clinical laboratories. AST results are interpreted using clinical breakpoints, which are updated to enable accurate detection of new and emerging AMR. Laboratories that do not apply up-to-date breakpoints impede global efforts to address the AMR crisis, but the extent of this practice is poorly understood. METHODS: A total of 1490 clinical laboratories participating in a College of American Pathologists proficiency testing survey for bacterial cultures were queried to determine use of obsolete breakpoints. RESULTS: Between 37.9% and 70.5% of US laboratories reported using obsolete breakpoints for the antimicrobials that were queried. In contrast, only 17.7%-43.7% of international laboratories reported using obsolete breakpoints (P < .001 for all comparisons). Use of current breakpoints varied by AST system, with more laboratories reporting use of current breakpoints in the US if the system had achieved US Food and Drug Administration clearance with current breakpoints. Among laboratories that indicated use of obsolete breakpoints, 55.9% had no plans to update to current standards. The most common reason cited was manufacturer-related issues (51.3%) and lack of internal resources to perform analytical validation studies to make the update (23.4%). Thirteen percent of laboratories indicated they were unaware of breakpoint changes or the need to update breakpoints. CONCLUSIONS: These data demonstrate a significant gap in the ability to detect AMR in the US, and to a lesser extent internationally. Improved application of current breakpoints by clinical laboratories will require combined action from regulatory agencies, laboratory accreditation groups, and device manufacturers.

The role of the medical laboratory director.

The American Medical Association notes in its Principles of Medical Ethics that a physician "shall be dedicated to provide competent medical service with compassion and respect for human dignity." As physicians whose profession involves the medical direction of pathology and clinical laboratory services, pathologists strive to provide high-quality, cost-effective services to support the needs of patient care. These services must be provided under the aegis of extensive legal and regulatory mandates of various governmental and nongovernmental entities. To accomplish his/her task, the pathologist can use tools of evidence-based medicine and clinical practice guidelines together with his/her medical and scientific training and experience. At the same time, the Medical Director must be able to measure and demonstrate the value of his/her contribution in today's competitive environment.

Laboratory accreditation and inspection.

Clinical laboratories perform diagnostic testing in a highly regulated environment in which federal, state, and private accreditation agencies monitor the quality of testing processes. These agencies vary in the focus and stringency of their requirements, and differences exist among states. Continued accreditation requires regular inspection to assure quality of test results for physicians, insurers, and, ultimately, the patients being tested. Preparation for inspection requires understanding of the unique accreditation requirements for each institution, establishment of quality assurance and quality improvement oversight, and communication of each staff member's role in delivering quality test results for patient care.

Toward High-Value Care: A Quality Improvement Initiative to Reduce Unnecessary Repeat Complete Blood Counts and Basic Metabolic Panels on a Pediatric Hospitalist Service.

OBJECTIVE: Achieving high-value health care is a goal of health care providers who strive to increase quality and decrease cost. Decreasing laboratory tests is a potential method to increase value. We used quality improvement methodology to decrease the percentage of unnecessary complete blood counts (CBCs) and basic metabolic panels (BMPs) obtained on a pediatric hospital medicine service from 13.5% to <5%. METHODS: A pre- and postintervention design was conducted including all patients admitted to 2 hospital medicine teams between May 2013 and December 2014. Multiple interventions linked to key drivers were tested through rapid plan-do-study-act cycles. Primary and secondary outcome measures, percent reduction of unnecessary CBCs and BMPs, and consecutive day tests were analyzed using statistical process control. Total billed charges, laboratory charges, 7-day readmission rates, and length of stay were compared pre- and postintervention. RESULTS: Primary outcome of unnecessary CBCs and BMPs was reduced from a baseline of 13.5% to 4.5%. Secondary outcome measure of consecutive day testing was reduced from 20.9% to 8.5%. Median laboratory charges decreased significantly ($842 [$256-$1863] vs $800 [$222-$1616], P = .002), with no significant differences in total billed charges, 7-day readmission rates, or length of stay. CONCLUSIONS: Rapid cycle plan-do-study-act methodology, initially focusing on the inclusion of a daily laboratory plan in progress notes, was an effective means to improve laboratory utilization and decrease laboratory charges without adversely affecting other quality measures. Spreading these efforts to different patient populations and laboratory tests could have a demonstrable effect on the value of health care.

Fatal BK polyoma viral pneumonia associated with immunosuppression.

BK polyoma virus has a worldwide distribution in the human population. Primary BK infection takes place during childhood, with the virus remaining latent in many sites. Immunosuppressive states can lead to viral reactivation associated with many clinical sequelae. We report a case of fatal BK-related pneumonia in a 69-year-old patient who was immunocompromised because of chemotherapy for chronic lymphocytic leukemia. Immunohistochemical, in situ hybridization, and polymerase chain reaction studies on paraffin-embedded lung tissue proved BK virus as the etiologic agent of pneumonia. The histological picture was remarkable for numerous intranuclear large basophilic viral inclusions with ground-glass appearance mainly in type II pneumocytes. Similar to many other infectious agents, BK virus is emerging as an important pathogen in immunocompromised patients, making it important to consider in the differential diagnosis.

Use of HIV resistance testing after prolonged treatment interruption.

BACKGROUND: HIV-1 genotypic resistance testing is not routinely recommended for patients who have been off antiretroviral therapy (ART) for longer than 4 weeks. We assessed the results and use of resistance testing in patients off ART. METHODS: All HIV resistance genotypes from November 2003 through April 2008 were reviewed from one large teaching hospital and two private HIV practices. Inclusion criterion was having a genotypic resistance test after an ART interruption of at least 2 months. Medical records were reviewed using a standardized data collection sheet. RESULTS: Sixty-two of 304 treatment-experienced patients with HIV genotypes met the inclusion criteria. Prior cumulative ART class exposure included nucleoside reverse transcriptase inhibitors in 54 patients, nonnucleoside reverse transcriptase inhibitors in 32 patients, and protease inhibitors in 30 patients. Resistance testing was performed at a mean of 12 months (range, 2.5-48 months) after ART interruption. The mean time between ART interruption and resistance testing did not differ for patients with mutations and those without mutations detected. Seventeen of 62 (27.4%) patients were found to have resistance mutations. Eleven patients were found to have mutations to nonnucleoside reverse transcriptase inhibitors, four patients had mutations to nucleoside reverse transcriptase inhibitors, and two patients had protease inhibitor-associated mutations. No patient had multiclass resistance. Among the 17 patients with mutations after treatment interruption, 15 had mutations that were either not present on a prior genotype (n = 2) or did not have a prior genotype (n = 13). CONCLUSIONS: HIV genotypic resistance assays may identify mutations even when performed after a prolonged treatment interruption and may offer clinically significant information. Current guidelines that discourage resistance testing after treatment interruptions of longer than 4 weeks should be re-evaluated.