Change in Quality of Tuberculosis (TB) Care since National Quality Assessment Program of TB Healthcare Service

Purpose: This study aims to examine the quality of tuberculosis (TB) care after the 1^st to 3^rd national quality assessment (QA) program for TB healthcare service in Korea was conducted.Methods: We analyzed Health Insurance Review & Assessment Service (HIRA) claims data of new TB patients during the period of January to June from 2018-2020. The new TB patients were defined as TB patients reported to Korea Centers for Disease Control and Prevention Agency (KCDA). The unit of analysis was the patient. Chi-square tests were used to analyze the differences in indicator value according to the types of medical facilities. The QA indicators of TB care were divided into 3 areas consisting of the following 7 quality indicators: 4 indicators of diagnosis test (the rate of acid-fast bacilli smear, the rate of acid-fast bacilli culture, the rate of Mycobacterium tuberculosis-polymerase chain reaction, drug susceptibility test), 1 compliance of treatment guideline, and 2 indicators of care management of TB patients (encounter rate, day of therapy).Results: The QA program for TB care was conducted among 8,246 patients from 534 facilities in 2020. The value of the 7 quality indicators was shown to increase as a result of the QA program. The indicators of the diagnostic test were all higher than 95%, with the exception of the drug susceptibility test which was 84.8%. Both indicators for care management of TB patients were 88.5%.Conclusion: The quality of TB care has been improving with the implementation of the QA program. In order to continue to improve the quality of TB care, it will be necessary to disclose the results of the QA program in medical facilities in the future.

Invasive Pulmonary Aspergillosis Due to Aspergillus Lentulus in a Liver Transplant Recipient: a Case Report and Literature Review

Background: Aspergillus lentulus, a new species discovered in 2005, is a rare fungal pathogen with reduced sensitivity to antifungal agents. Case presentation: Here we reported a 58-year-old male who underwent a liver transplantation on January 2020 and followed by maintenance immunosuppressive therapy. Then A.lentulus was cultured from his sputum twice and identified by using the MALDI-TOF-MS and confirmed by the reference of RUO database. In the susceptibility tests of the isolate, minimal inhibitory concentrations for amphotericin B, voriconazole, posaconazole, and caspofungin were found to be 0.5 mg/L, 1.0 mg/L, 0.5 mg/L and 8 mg/L, respectively. The patient was improved after treatment with a voriconazole 0.2g q12h orally plus caspofungin 50mg qd intravenously. Conclusion: A. lentulus is easily confused with A. fumigatus and its susceptibility to amphotericin B and azoles antifungal agents is reduced. Therefore, the identification of strain and drug susceptibility test are very important for clinical treatment.

Evaluating the Frequency of Resistance to Pyrazinamide Among Drug-resistant Strains of Mycobacterium tuberculosis in Isfahan, Iran

Background: Pyrazinamide is one of the most important first-line medications for the treatment of tuberculosis and an alternative intake for MDR-TB and XDR-TB patients. Objectives: The purpose of this study was to evaluate resistance to pyrazinamide in the isolates resistant to the Mycobacterium tuberculosis drug in patients in the city of Isfahan. Methods: In this study, the drug susceptibility test was performed with pyrazinamide using the proportion method and PZA assay on 47 isolates resistant to Mycobacterium tuberculosis. Then, the mutations of the pncA and rpsA genes of the isolates resistant to pyrazinamide were evaluated by the sequencing method. Results: According to the proportion method, 19 cases were resistant to pyrazinamide, 16 of which had mutations in their pncA and rpsA genes. Besides, five new mutations were recorded, and three isolates lacked mutations in the mentioned genes. Conclusions: Pyrazinamide resistance is high in MDR-TB and INH mono-resistant isolates. Therefore, evaluating the susceptibility to pyrazinamide in patients with MDR-TB before the initiation of treatment with pyrazinamide is considered essential.

Survival, Chemotherapy and Chemosensitivity Predicted by CTC Cultured In Vitro of SCLC Patients

PurposeThe prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured in vitro may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs.MethodsBased on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured in vitro obtained from ClearCell FX® System was tested and the therapy response was evaluated.ResultsAll of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease.ConclusionThe results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured in vitro may not benefit the improvement of therapeutic regimen of SCLC patients.

Tale of compounding oddities

We present a case of a 59-year-old man, who on being evaluated for abdominal pain and headache, was found to have a pancreatic head mass and inflammatory hypophysitis. Xpert MTB/Rif of the pancreatic mass biopsy showed the presence of tuberculosis (TB) with a very low load, and rifampicin resistance was detected with absence of probes A and B. Pyrosequencing (a novel genotypic test for TB) of the Xpert MTB/Rif isolate detected a single, rare, high-confidence mutation (S512T) in the rpoB region (rifampicin resistance determining region in the MTB genome). The TB mycobacteria growth indicator tube (TBMGIT) phenotypic drug susceptibility test (DST), however, showed rifampicin susceptibility. Incidentally, he was unable to tolerate rifampicin and responded well to a non-rifampicin-based regimen. We discuss a possible hypothesis of the Xpert-DST discordance in accordance with a recent literature review on phenotypic DST methods. We also discuss the utility of pyrosequencing in clinical practice for the diagnosis of TB and its resistance patterns.

Targeted-Sequencing Workflows for Comprehensive Drug Resistance Profiling of Mycobacterium tuberculosis Cultures Using Two Commercial Sequencing Platforms: Comparison of Analytical and Diagnostic Performance, Turnaround Time, and Cost

Background The emergence of Mycobacterium tuberculosis with complex drug resistance profiles necessitates a rapid and comprehensive drug susceptibility test for guidance of patient treatment. We developed two targeted-sequencing workflows based on Illumina MiSeq and Nanopore MinION for the prediction of drug resistance in M. tuberculosis toward 12 antibiotics. Methods A total of 163 M. tuberculosis isolates collected from Hong Kong and Ethiopia were subjected to a multiplex PCR for simultaneous amplification of 19 drug resistance-associated genetic regions. The amplicons were then barcoded and sequenced in parallel on MiSeq and MinION in respective batch sizes of 24 and 12 samples. A web-based bioinformatics pipeline, BacterioChek-TB, was developed to translate the raw datasets into clinician-friendly reports. Results Both platforms successfully sequenced all samples with mean read depths of 1,127× and 1,649×, respectively. The variant calling by MiSeq and MinION could achieve 100% agreement if variants with an allele frequency of <40% reported by MinION were excluded. Both workflows achieved a mean clinical sensitivity of 94.8% and clinical specificity of 98.0% when compared with phenotypic drug susceptibility test (pDST). Turnaround times for the MiSeq and MinION workflows were 38 and 15 h, facilitating the delivery of treatment guidance at least 17–18 days earlier than pDST, respectively. The higher cost per sample on the MinION platform ($71.56) versus the MiSeq platform ($67.83) was attributed to differences in batching capabilities. Conclusion Our study demonstrates the interchangeability of MiSeq and MinION platforms for generation of accurate and actionable results for the treatment of tuberculosis.