RESUMO
We implemented 2 interventions to improve utilization and contamination at our institution: kits to improve appropriate sample collection and an electronic order alert displaying appropriate indications of fungal blood cultures. An electronic order alert when ordering fungal blood cultures was associated with decreased utilization without decrease in positivity rate.
Assuntos
Hemocultura , Registros , HumanosRESUMO
Proteus mirabilis is a Gram-negative bacterium recognized for its unique swarming motility and urease activity. A previous proteomic report on four strains hypothesized that, unlike other Gram-negative bacteria, P. mirabilis may not exhibit significant intraspecies variation in gene content. However, there has not been a comprehensive analysis of large numbers of P. mirabilis genomes from various sources to support or refute this hypothesis. We performed comparative genomic analysis on 2,060 Proteus genomes. We sequenced the genomes of 893 isolates recovered from clinical specimens from three large US academic medical centers, combined with 1,006 genomes from NCBI Assembly and 161 genomes assembled from Illumina reads in the public domain. We used average nucleotide identity (ANI) to delineate species and subspecies, core genome phylogenetic analysis to identify clusters of highly related P. mirabilis genomes, and pan-genome annotation to identify genes of interest not present in the model P. mirabilis strain HI4320. Within our cohort, Proteus is composed of 10 named species and 5 uncharacterized genomospecies. P. mirabilis can be subdivided into three subspecies; subspecies 1 represented 96.7% (1,822/1,883) of all genomes. The P. mirabilis pan-genome includes 15,399 genes outside of HI4320, and 34.3% (5,282/15,399) of these genes have no putative assigned function. Subspecies 1 is composed of several highly related clonal groups. Prophages and gene clusters encoding putatively extracellular-facing proteins are associated with clonal groups. Uncharacterized genes not present in the model strain P. mirabilis HI4320 but with homology to known virulence-associated operons can be identified within the pan-genome. IMPORTANCE Gram-negative bacteria use a variety of extracellular facing factors to interact with eukaryotic hosts. Due to intraspecies genetic variability, these factors may not be present in the model strain for a given organism, potentially providing incomplete understanding of host-microbial interactions. In contrast to previous reports on P. mirabilis, but similar to other Gram-negative bacteria, P. mirabilis has a mosaic genome with a linkage between phylogenetic position and accessory genome content. P. mirabilis encodes a variety of genes that may impact host-microbe dynamics beyond what is represented in the model strain HI4320. The diverse, whole-genome characterized strain bank from this work can be used in conjunction with reverse genetic and infection models to better understand the impact of accessory genome content on bacterial physiology and pathogenesis of infection.
Assuntos
Proteômica , Proteus mirabilis , Humanos , Proteus mirabilis/genética , Filogenia , Virulência/genética , Fatores de Virulência/genéticaRESUMO
An isolate of Morganella morganii (MMOR1) that tested susceptible to 3rd/4th-generation cephalosporins and intermediate to meropenem was characterized as positive for NDM and IMP carbapenemases by NG-Test CARBA 5. Our objective was to further investigate this result, given the inconsistent susceptibility profile and unusual epidemiological profile for our region. The MMOR1 isolate was retested for antimicrobial susceptibilities and characterized for carbapenemase production. MMOR1 tested susceptible to ceftazidime, ceftriaxone, cefepime, aztreonam, and ertapenem, and intermediate to meropenem and imipenem. The isolate tested positive by carbapenem inactivation method (CIM) and CIM+EDTA (eCIM) testing, indicating metallo-ß-lactamase production. The isolate tested negative for all carbapenemase genes on Xpert Carba-R, but positive for IMP on repeat testing of NG-Test CARBA 5. Whole-genome sequencing revealed MMOR1 contained blaIMP-27, but no other carbapenemase genes. Additional testing with NG-Test CARBA 5 revealed a false-positive NDM band when the assay was overloaded with test inoculum. Supplementary isolates were tested with an overloaded inoculum (n = 6 M. morganii; n = 1 P. mirabilis; n = 1 IMP-27-producing P. rettgeri; n = 1 IMP-1-producing E. coli; n = 1 K. pneumoniae), and two non-carbapenemase-producing carbapenem non-susceptible M. morganii also generated a false-positive NDM band; though, this was not universal among this species. A dual IMP+/NDM+ M. morganii is an unusual result that should prompt additional investigation, especially in nonendemic regions and when the susceptibility profile is incompatible. IMP-27 is not detected by Xpert Carba-R but is variably detected by NG-Test CARBA 5. The microorganism inoculum used for NG-Test CARBA 5 must be carefully controlled for accurate results. IMPORTANCE The detection of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) is an important function of the clinical microbiology laboratory, where positive identifications have immediate implications for infection control and surveillance strategies in the inpatient setting and can inform appropriate selection of therapy among the various novel anti-CP-CRE agents. NG-Test CARBA 5 is a relatively new lateral flow assay used for detection of carbapenemases in CP-CRE. Here, we describe the characterization of a Morganella morganii isolate that generated a false-positive NDM carbapenemase detection by this assay, and perform bacterial test inoculum experiments with additional isolates to further investigate a cause of false-positive results using the NG-Test CARBA 5. While a lateral flow assay like the NG-Test CARBA 5 is a very desirable test format for clinical laboratories, there are pitfalls to avoid when performing this test and interpreting results, including recognizing an overloaded test assay, which could lead to false-positive results.
Assuntos
Morganella morganii , Meropeném , Morganella morganii/genética , Escherichia coli , Proteínas de Bactérias/genética , beta-Lactamases/genética , Imipenem , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologiaRESUMO
BACKGROUND: Cefiderocol is a new antibiotic used to treat infections with antibiotic resistant Gram-negative bacilli. The impact of differences between Mueller-Hinton agar (MHA) brands on susceptibility testing is underexplored. Compounding the implementation of cefiderocol susceptibility testing is a lack of harmonization between different regulatory body breakpoint criteria. METHODS: We performed Kirby-Bauer disk diffusion using BD, Hardy, and Remel MHA, in addition to broth microdilution for Acinetobacter baumannii (n = 25), Enterobacterales (n = 25), Stenotrophomonas maltophilia (n = 24), and Pseudomonas aeruginosa (n = 23). We analyzed disk diffusion diameters and minimum inhibitory concentrations using interpretive criteria from the Clinical and Laboratory Standards Institute (CLSI), US Food and Drug Administration (FDA), and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). RESULTS: Breakpoint criteria impacted interpretation of susceptibly testing results, for example with the broth microdilution we found 8% (2/25) of A. baumannii isolates change interpretation between CLSI and EUCAST and 32% (8/25) change between CLSI and FDA, 12% (3/25) of Enterobacterales change between CLSI and EUCAST, 13% (3/23) of P. aeruginosa interpretations change between CLSI and FDA, and 4% (1/25) S. maltophilia change between CLSI and FDA. There was a significant difference between the zone disk diffusion diameters for P. aeruginosa and S. maltophilia between Hardy and BD; which changed interpretation (using CLSI criteria) for 8.7% (2/23) for P. aeruginosa but 0% (0/24) for S. maltophilia. CONCLUSIONS: Breakpoint criteria impact cefiderocol susceptibility testing interpretation for broth microdilution and disk diffusion. Choice of MHA brand can also affect result interpretation.
Assuntos
Antibacterianos , Cefalosporinas , Estados Unidos , Humanos , Ágar , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , CefiderocolRESUMO
Persistent Staphylococcus aureus bacteremia (SAB) has been associated with increased mortality. Enhanced microbial detection with new blood culture technology may improve detection of S. aureus in patients with SAB. We performed a 24-month retrospective study of hospitalized adults with SAB and an infectious diseases consult comparing two time periods pre- (January to December 2018) and postimplementation (January to December 2019) in which the VersaTREK and BacT/Alert Virtuo blood culture systems were used, respectively. Measurements included SAB duration, time to positivity, source of bacteremia, antimicrobial therapy, and mortality. A total of 416 episodes of SAB occurred during the study period: 176 (42%) pre- and 240 (58%) postimplementation. Patients in both periods had similar clinical characteristics; however, patients in the postimplementation period were more likely to have intermediate (3 to 6 days; 23% versus 40%; P < 0.001) and prolonged SAB duration (>7 days; 4% versus 14%; P < 0.001). Combination antistaphylococcal therapy was more frequent postimplementation (6.3% pre- versus 15.8% postimplementation; P = 0.003), and the median time to source control was shorter (4 versus 2 days; P = 0.02). Median time to positivity for the index blood culture was shorter postimplementation (17.8 h pre- versus 13.3 h postimplementation; P < 0.001). There was no difference in 90-day all-cause readmissions (51% versus 44%; P = 0.11) or mortality (32% versus 32%; P = 0.95). An increased frequency of prolonged SAB with increased use of combination antistaphylococcal therapy was noted with implementation of a new blood culture system, likely secondary to the blood culture media; however, no differences on adverse outcomes were noted.
Assuntos
Bacteriemia , Infecções Estafilocócicas , Adulto , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Hemocultura , Meios de Cultura , Humanos , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureusRESUMO
BACKGROUND: The urinary tract is not sterile and is populated by microbial communities that influence urinary health. Men who have sex with men (MSM) are understudied yet have increased risk factors for genitourinary infections. Our objective was to interrogate the composition of MSM urinary microbiota. METHODS: Midstream urine specimens (n = 129) were collected from MSM (n = 63) and men seen for routine care (clinical cohort, n = 30). Demographics and sexual/medical history were documented. Specimens underwent culture using standard-of-care and enhanced methods designed to isolate fastidious and anaerobic microorganisms. Isolates were identified by MALDI-TOF mass spectrometry or 16S rRNA gene sequencing. RESULTS: The MSM cohort was younger (mean (SD), 35.4 (11.26) years) compared to the clinical cohort (62.7 (15.95) years). Organism recovery was significantly increased using enhanced vs standard culture for the MSM (mean of 9.1 vs 0.6 species/sample [P < 0.001]) and clinical (7.8 vs 0.9 species/sample [P < 0.001]) cohorts. The microbial composition of MSM urine specimens was dominated by Gram-positive and anaerobic microbes and clustered distinctly from that of clinical urine specimens. Composition of microbial species recovered within the same subject was dynamic between urine specimens but more similar relative to inter-individual comparisons. Principal coordinate analysis showed no correlation between urinary microbiota composition and age, recent antibiotic use, sexually transmitted infection/HIV status, or sexual practices. CONCLUSIONS: Enhanced culture recovered a large diversity of microbial species from MSM urine specimens, especially taxa typically associated with mucosal surfaces. These findings may increase understanding of urologic disease in MSM and improve diagnostic methods for detection of genitourinary infections.
Assuntos
Microbiota , Minorias Sexuais e de Gênero , Infecções Urinárias , Homossexualidade Masculina , Humanos , Masculino , RNA Ribossômico 16S/genética , Infecções Urinárias/diagnósticoRESUMO
The bioMérieux BacT/Alert Virtuo blood culture system used in combination with resin-containing media may enhance the growth of microorganisms. Our objective was to assess the impact of transitioning to the Virtuo system in comparison to the VersaTREK blood culture system at a tertiary care medical center. We retrospectively reviewed all blood cultures performed at a 1,250-bed academic medical center between January and December 2018 (VersaTREK) and January and December 2019 (Virtuo). Blood culture positivity rates and contamination rates were compared before and after Virtuo implementation. Of 101,438 blood cultures performed during the study period, 48,839 (48.1%) were processed preimplementation and 52,599 (51.9%) postimplementation. The blood culture positivity rate increased from 8.1% preimplementation to 11.7% postimplementation (P < 0.001). Staphylococcus aureus was the most frequently isolated species in both time periods and had a higher recovery rate postimplementation (1.5% of all blood cultures obtained preimplementation versus 3.4% postimplementation; P < 0.001). A higher recovery rate in the postimplementation period was also noted for coagulase-negative staphylococci (1.9% preimplementation versus 2.7% postimplementation; P < 0.001), as well as modest but statistically significant changes for Escherichia coli (0.8% versus 1.0%; P < 0.001), Klebsiella pneumoniae (0.4% versus 0.5%; P = 0.005), and Candida albicans. (0.1% versus 0.2%; P = 0.038). The inpatient blood culture contamination rate was higher postimplementation (1.5% preimplementation versus 1.9% postimplementation; P < 0.001). The Virtuo blood culture system was associated with a higher observed proportion of positive blood cultures than the VersaTREK system. Future studies are needed to assess whether an increased rate of positive blood cultures is associated with changes in clinical outcomes.
Assuntos
Bacteriemia , Hemocultura , Bacteriemia/diagnóstico , Meios de Cultura , Humanos , Estudos Retrospectivos , Staphylococcus aureus , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Polymicrobial blood stream infection is often considered uncommon, and corresponding cultures may be assumed to represent contamination. Here we characterized the prevalence and epidemiology of these cultures submitted to a central clinical microbiology laboratory. METHODS: Blood cultures from 2017 to 2018 (n = 104 547) were evaluated. Polymicrobial blood cultures were defined by the presence of more than one organism in a blood culture set (set = one aerobic and one anaerobic bottle). Data were stratified by patient location and characteristics of the microbiota detected. RESULTS: Of all blood culture sets, 14 600 (14.0%) were positive. Among these, 1651 sets (11.3% of positive cultures; 1.6% of total cultures) were polymicrobial. Most cultures (85.2%) grew two microorganisms; the greatest number of microorganisms in a culture was 6. The most common microorganism pairs were (a) two coagulase-negative staphylococci (CoNS), (b) Corynebacterium and CoNS, and (c) S. aureus and CoNS. Microorganisms in polymicrobial cultures represented microbiota from skin (46.1%), the gastrointestinal (GI) tract (33.9%), strict anaerobes (1.4%), and "other" microorganisms (18.6%). Most cultures with GI microbiota originated from an adult academic medical center compared to community or pediatric settings (40.5% of polymicrobial cultures vs 27.2% and 25.8%, P < 0.0001). Within the academic medical center, patients in an intensive care unit (ICU) or who had bone marrow transplants (BMT) had more cultures suggestive of GI microbiota compared to those from the emergency department (ED) (50.8% and 52.8% vs 31.2%, P < 0.0001). CONCLUSIONS: Polymicrobial blood cultures are common in a variety of healthcare settings and the recovered microorganisms can be clinically relevant.
Assuntos
Bacteriemia , Hemocultura , Adulto , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Criança , Atenção à Saúde , Humanos , Laboratórios , Staphylococcus aureusRESUMO
New blood culture instrumentation and medium formulations have led to improved time to positivity (TTP) for positive blood cultures. Data regarding the necessity of pediatric blood culture bottles with contemporary blood culture systems are sparse. We compared performance of three commercial blood culture systems, evaluating impact of blood volumes in standard and pediatric blood culture media across systems. Simulated blood cultures with packed red blood cells (PRBCs) and three Gram-positive, four Gram-negative, and one anaerobic organism (final concentrations ranging from 0.5 to 19 CFU/ml blood) on the Virtuo, VersaTrek, and Bactec FX instruments were evaluated with FAN Plus, Redox, and Bactec Plus media, respectively. For each medium/instrument/organism combination, 1-, 3-, 5-, and 10-ml blood volumes were evaluated in triplicate. Detection rate was not affected by blood volume. Aerobic organisms that demonstrated variable rates of detection were Kingella kingae, Haemophilus influenzae, and Neisseria meningitidis. Bacteroides fragilis was detected in 83%, 100%, and 100% of Virtuo, VersaTrek, and Bactec anaerobic bottles, respectively. The average TTP of standard medium for aerobic organisms detected on Virtuo was decreased compared to those for VersaTrek (-2.3 h) and Bactec (-4.9 h). Compared to standard medium, detection rate and TTP were unchanged on Virtuo, while TTP was reduced with pediatric medium for 2/8 organisms tested on Bactec and 7/8 organisms on VersaTrek, illustrating the potential benefit of pediatric medium on VersaTrek or Bactec when low blood volumes (<5 ml) are collected. These results demonstrate that TTP is decreased on the Virtuo compared to VersaTrek and Bactec for many microorganisms associated with bloodstream infection (BSI) but may have species-specific limitations.
Assuntos
Bacteriemia , Infecções Bacterianas , Sepse , Bacteriemia/diagnóstico , Técnicas Bacteriológicas , Hemocultura , Criança , Meios de Cultura , HumanosAssuntos
Catarata/etiologia , Exantema/etiologia , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico , Trombocitopenia/etiologia , Feminino , Hematopoese Extramedular , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Recém-NascidoRESUMO
BACKGROUND: Every clinical specimen is potentially infectious, but data regarding risk for contamination of the laboratory environment during routine testing are scarce. We assessed contamination during routine sample analysis in automated clinical chemistry and microbiology laboratories. METHODS: A fluorescent marker was applied to specimen container exteriors to assess the impact of gross contamination. Nonpathogenic MS2 virus was added to remnant blood, urine, and ESwab matrices as a biomarker of cross-contamination. Samples were processed and analyzed using Roche Cobas 8100 and ISE, c502, e602, and c702 modules (blood) and BD Kiestra total laboratory automation (blood, urine, ESwabs) over 3 experiments. Fluorescence transfer to laboratory surfaces and personnel was visualized using ultraviolet light. Surfaces were swabbed and assessed for MS2 cross-contamination by RT-PCR. Adherence to standard precautions by laboratory staff was assessed by observation. RESULTS: Fluorescence was observed on 49 of 165 (30%) laboratory surfaces and personnel and 21 of 93 (23%) total laboratory automation instruments. Fluorescence transferred most frequently to gloves (31/40), computer accessories (9/18), and specimen loading racks (12/12). None of 123 areas swabbed were positive for MS2. Improper personal protective equipment use occurred at a rate of 0.36 and 0.15 events per staff per hour in the chemistry and microbiology laboratories, respectively. Hand-washing compliance was observed for 61 of 132 (46%) staff members evaluated. CONCLUSIONS: Analysis of grossly contaminated specimens on automated chemistry and microbiology equipment elicits a low likelihood of instrument contamination. However, handling contaminated specimen containers can result in contamination of environmental laboratory surfaces, representing a source of risk that is heightened by low adherence to appropriate personal protective equipment.
Assuntos
Automação Laboratorial/instrumentação , Contaminação de Equipamentos , Fômites/virologia , Técnicas de Laboratório Clínico/instrumentação , Técnicas de Laboratório Clínico/métodos , Fluorescência , Corantes Fluorescentes/química , Higiene das Mãos , Humanos , Laboratórios , Levivirus , Técnicas Microbiológicas/instrumentação , Técnicas Microbiológicas/métodos , Medição de Risco , Manejo de EspécimesAssuntos
Betacoronavirus/isolamento & purificação , Técnicas de Diagnóstico Molecular/instrumentação , Técnicas de Diagnóstico Molecular/métodos , Betacoronavirus/genética , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Humanos , Nasofaringe/virologia , RNA Viral/genética , RNA Viral/isolamento & purificação , Kit de Reagentes para Diagnóstico , SARS-CoV-2RESUMO
Rapid diagnostic testing (RDT) can facilitate earlier optimization of the treatment of bloodstream infections, particularly in conjunction with an effective antimicrobial stewardship program (ASP). However, the effective implementation and workflow of RDTs are still a matter of debate, particularly in a pediatric setting. In this issue of the Journal of Clinical Microbiology, L. J. Juttukonda, S. Katz, J. Gillon, J. Schmitz, and R. Banerjee (J Clin Microbiol 58:e01400-19, 2020, https://doi.org/10.1128/JCM.01400-19) investigate the impact of a multiplex, molecular RDT on changes to antimicrobial therapy in an academic children's hospital. These data reveal several factors that clinical laboratories should consider prior to the implementation of RDTs for positive blood cultures.
Assuntos
Anti-Infecciosos , Infecções , Antibacterianos , Hemocultura , Criança , Testes Diagnósticos de Rotina , HumanosRESUMO
Uncommon fungi can cause opportunistic infections and are often unidentifiable using phenotypic methods. Molecular techniques, like DNA sequencing, may permit species-level identification but results may be challenging to interpret. To determine the clinical impact of molecular identification in this setting, we performed a retrospective review of fungal isolates referred for molecular identification. Seventy-five distinct fungal species were identified from 93 referred isolates, 31 (41%) of which are not known to be human pathogens. DNA sequencing prompted change in anti-infective therapy in only 3 (3.5%) cases but significantly delayed culture turnaround time (40⯱â¯31 vs. 30⯱â¯13â¯days, Pâ¯<â¯0.001). Patient immune status and concurrent histologic or serologic testing significantly correlated with the proportion of pathogenic isolates recovered and patients treated (χ2, Pâ¯<â¯0.05). Molecular identification of uncommon fungal isolates should be limited to specialized clinical settings such as patients with immunosuppression and/or concurrent positive histology or fungal serology.
Assuntos
Fungos/classificação , Micoses/microbiologia , Leveduras/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Feminino , Fungos/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Tipagem Micológica , Estudos Retrospectivos , Análise de Sequência de DNA , Leveduras/isolamento & purificação , Adulto JovemRESUMO
Carbapenem-resistant Enterobacteriaceae (CRE) are an important public health and infection prevention threat. CRE are typically detected via phenotypic antimicrobial susceptibility testing (AST), for which interpretive standards were modified in recent years. Our objective was to measure the impact of breakpoint changes on AST interpretation for CRE. Zone sizes from disk diffusion AST for Enterobacteriaceae isolates recovered from clinical cultures over a 1-year period (n = 10,183) and CRE from clinical and environmental sources from the USA and Pakistan (n = 342) were evaluated. Results were interpreted according to historical (CLSI M100-S19) and current (CLSI M100-S29) breakpoints. Interpretive errors were calculated according to the FDA definitions. Using current breakpoints as the reference standard, 56 (17%) very major (false susceptibility) errors occurred for cefepime and 13 (45%) very major errors for meropenem interpretation using historical breakpoints in clinical isolates of Enterobacteriaceae, corresponding to 12 carbapenemase-producing CRE that would have been missed during the 1-year period. For confirmed blaKPC CP-CRE clinical and environmental isolates (n = 149), the very major error rate for historic breakpoints was 8%, 30%, 63%, and 0% for cefepime, meropenem, imipenem, and ertapenem, respectively. For blaKPC isolates, the use of historical breakpoints would have led to 42 (28%) reports of false susceptibility to meropenem. Failure to adopt updated AST breakpoints may lead to reports of false susceptibility for antimicrobials commonly used to treat Gram-negative infections and preclude recognition of CRE. Such errors could negatively impact patient care and hamper infection control and public health efforts.
Assuntos
Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Carbapenêmicos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Infecções por Enterobacteriaceae/microbiologia , Humanos , Paquistão , Estados Unidos , beta-LactamasesRESUMO
BACKGROUND: The diagnosis of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis relies on the detection of NMDAR IgG autoantibodies in the serum or cerebrospinal fluid (CSF) of symptomatic patients. Commercial kits are available that allow NMDAR IgG autoantibodies to be measured in local laboratories. However, the performance of these tests outside of reference laboratories is unknown. OBJECTIVES: To report an unexpectedly low rate of NMDAR autoantibody detection in serum from patients with anti-NMDAR encephalitis tested using a commercially available diagnostic kit in an exemplar clinical laboratory. METHODS: Paired CSF and serum samples from seven patients with definite anti-NMDAR encephalitis were tested for NMDAR IgG autoantibodies using commercially available cell-based assays run according to manufacturer's recommendations. Rates of autoantibody detection in serum tested at our center were compared with those derived from systematic review and meta-analyses incorporating studies published during or before March 2019. RESULTS: NMDAR IgG autoantibodies were detected in the CSF of all patients tested at our clinical laboratory but not in paired serum samples. Rates of the detection were lower than those previously reported. A similar association was recognized through meta-analyses, with lower odds of NMDAR IgG autoantibody detection associated with serum testing performed in nonreference laboratories. CONCLUSIONS: Commercial kits may yield lower-than-expected rates of NMDAR IgG autoantibody detection in serum when run in exemplar clinical (nonreference) laboratories. Additional studies are needed to decipher the factors that contribute to lower-than-expected rates of serum positivity. CSF testing is recommended in patients with suspected anti-NMDAR encephalitis.
Effectuer en pratique clinique des tests visant à mesurer les anticorps anti-récepteurs NMDA. Contexte: Le diagnostic de l'encéphalite limbique avec anticorps anti-récepteurs NMDA repose sur la détection d'autoanticorps de classe IgG dans le sérum ou le liquide céphalo-rachidien des patients symptomatiques. Il existe certes des trousses commerciales qui permettent de mesurer ces autoanticorps dans des laboratoires locaux. Cependant, l'efficacité de ces tests en dehors de laboratoires homologués demeure inconnue. Objectif: Signaler un taux d'autoanticorps étonnamment faible dans le sérum de patients atteints d'encéphalite limbique avec anticorps anti-récepteurs NMDA, et ce, au moyen d'une trousse diagnostique commerciale utilisée dans un laboratoire clinique de haut niveau. Méthodes: En suivant les recommandations d'un fabricant, nous avons testé les échantillons appariés de liquide céphalo-rachidien et de sérum de sept patients atteints d'encéphalite limbique avec anticorps anti-récepteurs NMDA. À l'aide d'un bio-essai cellulaire, l'objectif était alors de détecter dans notre centre des autoanticorps de classe IgG et de comparer nos résultats à ceux obtenus à la suite d'une synthèse systématique et de méta-analyses incluant des études publiées au cours du mois de mars 2019 ou avant cette période. Résultats:Des autoanticorps de classe IgG en lien avec des anticorps anti-récepteurs NMDA ont été détectés dans le liquide céphalo-rachidien de tous les patients qui ont fait l'objet d'un test dans notre laboratoire clinique mais non pas dans les échantillons de sérum appariés. Les taux de détection se sont révélés plus faibles que ceux signalés précédemment. Nous avons observé une association similaire lors de méta-analyses, la probabilité de détecter des autoanticorps de classe IgG en lien avec des anticorps anti-récepteurs NMDA étant plus faible lorsqu'associée à des tests de sérum réalisés dans des laboratoires non homologués. Conclusions: Il est donc possible que les trousses commerciales ne débouchent sur des taux de détection d'autoanticorps de classe IgG plus faibles dans les sérums lorsqu'elles sont utilisées dans des laboratoires cliniques de haut niveau qui ne sont pas homologués. Des études complémentaires sont nécessaires pour mieux comprendre les facteurs qui contribuent à ces taux de positivité sérique plus bas que prévus. Enfin, des tests du liquide céphalo-rachidien sont recommandés chez des patients dont on soupçonne qu'ils sont atteints d'encéphalite limbique avec anticorps anti-récepteurs NMDA.
RESUMO
Fast, sensitive molecular diagnostic tests that use urine or self-collected swabs may lead to more screening opportunities and be more acceptable to patients, resulting in faster and more accurate diagnosis and treatment of gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium infection.