Ophthalmic manifestations are associated with reduced tear lymphotoxin-α levels in chronic ocular graft-versus-host disease

Purpose To determine the role tear lymphotoxin-α (LT-α) in chronic ocular graft-versus-host disease (oGVHD). Methods Twenty-two chronic oGVHD and 17 control tear samples were collected, and commercial test strips were used to detect LT-α concentrations. Concentration differences between patients with and without oGVHD were determined via Mann-Whitney U test. The correlation between LT-α levels and ophthalmic parameters was analyzed using Spearman’s test. Results The concentration of LT-α was significantly lower in oGVHD patients than in controls. LT-α levels were significantly correlated with OSDI, NIH eye score, T-BUT, and CFS among all participants. ROC analysis revealed that the area under the curve of LT-α was 0.847, and the cutoff value for chronic oGVHD diagnosis was 0.203 ng/mL. Conclusion Our study revealed the significant decrease of tear LT-α in oGVHD, and suggested LT-α as a promising marker for chronic oGVHD diagnosis.

786. Facility Reported vs. CLSI MIC Breakpoint Comparison of Carbapenem Non-susceptible (Carb-NS) Pseudomonas aeruginosa (PSA) From 2016-2019: A Multicenter Evaluation

Background CLSI lowered Pseudomonas aeruginosa (PSA) Carbapenem (Carb) interpretive breakpoint minimum inhibitory concentrations (MICs) in 2012. It often takes several years for commercial test manufacturers and microbiology labs to incorporate revised breakpoints. We compare facility-reported rates of Carb-NS PSA to the 2012 CLSI MIC breakpoints, using a large nationwide database for isolates tested in 2016-2020 at United States (US) facilities. Table. Imipenem (IPM)/meropenem (MEM)/doripenem (DOR) interpretation (evaluable isolates) results for PSA. Methods All adults with a positive non-contaminant PSA culture (first isolate per 30-day period from blood, respiratory, urine, skin/wound, intra-abdominal, or other) in ambulatory and inpatient settings from 298 US hospitals from Q1 2016-Q4 2020 were evaluated (BD Insights Research Database, Becton, Dickinson & Company). Facility-reported Carb-non susceptible (NS) was defined as lab information system feed designations of susceptible (S), intermediate (I) or resistant (R) to imipenem (IPM), meropenem (MEM) and/or doripenem (DOR) per commercial panels. Where available, MICs were interpreted using CLSI 2012 Carb breakpoints (µg/ml) of ≤2 (S), 4 (I), ≥8 (R) for IPM/MEM/DOR. For evaluable PSA isolates we compared susceptibility results as reported by the facility to those using CLSI MIC breakpoints. Results Overall, 86.9% (255,844/294,426) of non-duplicate PSA isolates with facility-reported IPM/MEM/DOR susceptibility interpretations also had interpretable MIC results. S rates were 84.9% and 83.3% as reported by facilities and determined by CLSI criteria, respectively (Table). Facilities under-reported Carb-NS by 9.8%, using CLSI criteria as the standard (10.4% and 7.7% of R and I isolates, respectively, were missed by facility reporting). Conclusion Systematic application of CLSI breakpoints in 2016-20 would have had minimal impact on PSA S rates in the US. However, facility reporting failed to identify ~10% of Carb-NS isolates. The clinical implications of this observation are unknown. Facilities should know their local epidemiology, decide if under-reporting might be an issue, and assess if there is any impact on their patients. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder) Kalvin Yu, MD, BD (Employee) Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Janet Weeks, PhD, Becton, Dickinson and Company (Employee) Cornelius J. Clancy, MD, Merck (Grant/Research Support)

Detection of Direct Oral Anticoagulants in Patient Urine Samples by Prototype and Commercial Test Strips for DOACs – A Systematic Review and Meta-analysis

The DOAC Dipstick accurately detects the presence or absence of factor Xa (DXI) and thrombin inhibitor (DTI) classes of direct oral anticoagulants (DOACs) in patients' urine samples on DOAC treatment. The aim of the study was to systematically review the literature and compare the performance of prototype and commercial test strips with a meta-analysis.A systematic literature search of electronic databases PubMed (MEDLINE) and Cochrane Library was performed. Heterogeneity between studies was calculated using the Chi-squared test and the I2 index. A random effects model was used to pool data to compare the performance of prototype and commercial test strips.Using PRISMA reporting guidelines, four of 1,081 publications were eligible for inclusion in the meta-analysis: three reporting on prototype (DXI n = 658, DTI n = 586) and one on commercial test strips (DXI n = 451, DTI n = 429). Sensitivity and specificity of DXI and DTI detection did not differ significantly between the prototype and commercial test strips. Odds ratios were 0.718 and 0.365 for sensitivity and 1.211 and 1.072 for specificity of DXI and DTI (p-values between 0.3334 and 1.000), respectively. The pooled sensitivity and specificity values for DXI were 0.968 (p = 0.1290, I2 47.1%) and 0.979 (p = 0.1965, I2 35.9%), and for DTI 0.993 (p = 0.1870, I2 37.5%) and 0.993 (p = 0.7380, I2 0%), respectively.Prototype and commercial DOAC test strips did not differ in their ability to detect DXI and DTI in patient urine samples. This supports the confidence in use of the DOAC Dipstick test, although it needs to be validated in specific patient populations.

Stenotrophomonas maltophilia susceptibility testing challenges and strategies

Stenotrophomonas maltophilia is intrinsically resistant to many beta lactam antibiotics including carbapenems and is resistant to aminoglycosides, which limits the therapeutic repertoire for managing S. maltophilia infections. Additionally, employing automated in vitro susceptibility testing of S. maltophilia is challenging because commercial test systems’ performance is limited (A. Khan, C. A. Arias, A. Abbott, J. Dien Bard, et al., J Clin Microbiol 59:e00654-21, 2021, https://doi.org/10.1128/JCM.00654-21 ). This commentary will briefly discuss the opportunity to use automated commercial susceptibility testing systems with S. maltophilia with a focus on how to practically implement their use while mitigating risk of error.

Rapid detection of Clostridium perfringens in food by loop-mediated isothermal amplification combined with a lateral flow biosensor

Clostridium perfringens is a key anaerobic pathogen causing food poisoning. Definitive detection by standard culture method is time-consuming and labor intensive. Current rapid commercial test kits are prohibitively expensive. It is thus necessary to develop rapid and cost-effective detection tool. Here, loop-mediated isothermal amplification (LAMP) in combination with a lateral-flow biosensor (LFB) was developed for visual inspection of C. perfringens-specific cpa gene. The specificity of the developed test was evaluated against 40 C. perfringens and 35 other bacterial strains, which showed no cross-reactivity, indicating 100% inclusivity and exclusivity. LAMP-LFB detection limit for artificially contaminated samples after enrichment for 16 h was 1–10 CFU/g sample, which was comparable to the commercial real-time PCR kit. The detection performance of LAMP-LFB was also compared to culture-based method using 95 food samples, which revealed the sensitivity (SE), specificity (SP) and Cohen's kappa coefficient (κ) of 88.0% (95% CI, 75.6%-95.4%), 95.5% (95% CI, 84.8%-99.4%) and 0.832 (95% CI, 0.721–0.943), respectively. Area under the receiver operating characteristic (ROC) curve was 0.918 (95% CI, 0.854–0.981), indicating LAMP-LFB as high relative accuracy test. In conclusion, LAMP-LFB assay is a low-cost qualitative method and easily available for routine detection of C. perfringens in food samples, which could serve as an alternative to commercial test kit.

Delayed hypersensitivity reaction to orodispersible budesonide in a case with eosinophilic esophagitis

Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disease that has been known since the early 1990s. Swallowed topical corticosteroids (STC) belong to the therapeutic cornerstones. We describe a delayed hypersensitivity reaction to Jorveza®, a newly developed orodispersible budesonide tablet licensed for the treatment of eosinophilic esophagitis. Case presentation A 32-year-old Caucasian woman with EoE was newly treated with Jorveza®. Hours after the first intake, she felt a “strange pruritus” in the throat. This sensation worsened with each subsequent intake. On day 4 she developed oral mucosal symptoms (paresthesia of the tongue, sore and an itchy throat). Intraoral, throat and facial swellings, but no systemic reaction were observed. Patch testing using two commercial test series as well as the orodispersible budesonide tablet revealed a strong sensitization, proving a T cell mediated allergy to budesonide. Conclusions Orodispersible budesonide is increasingly prescribed for the treatment of eosinophilic esophagitis. The development of oropharyngeal symptoms after initiating should alert the treating physician to the possibility of a hypersensitivity reaction.

Antibiotic Residues in Filtered Honeys

In this study, tetracycline and streptomycin group antibiotic residues were investigated in packaged and open sold honey. For this purpose, a total of 60 honey samples, which were 30 of each were used as material. Honey samples were taken from various sales places located in Sivas province. ELISA method was used for the analysis and commercial test kits were used. According to the analysis results; tetracycline was found in 73.3% (22 samples) of the packaged honey and streptomycin was found in all samples. Tetracycline and streptomycin were determined as positive in open honeys were respectively 60% (18 samples) and 93.3% (28 samples). Tetracycline levels were between 0.12-371.43 ppb (mean 13.91 ± 12.33) in packaged honey and 0.02-13.32 ppb (mean 1.75 ± 0.5) in open honeys. Streptomycin levels were 1.30-250.2 ppb (mean 25.8 ± 10.8) in packaged honey and 0.19-22.71 ppb (mean 8.21 ± 5.2) in open honeys. Antibiotic residue was not found in one sample of open honeys. The findings suggest that, although illegal, some medicines are used in beekeeping or that bees are exposed to antibiotics that are added to the feed or water of other animals. These findings pose a potential risk to the consumer.