Clinical Features of Adult COVID-19 Patients without Risk Factors before and after the Nationwide SARSCoV-2 B.1.617.2 (Delta)-variant Outbreak in Korea: Experience from Gyeongsangnam-do

Background@#Data on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) delta variant virulence are insufficient. We retrospectively compared the clinical features of adult coronavirus disease 2019 (COVID-19) patients without risk factors for severe COVID-19 who entered residential treatment centers (RTCs) before and after the delta variant outbreak. @*Methods@#We collected medical information from two RTCs in South Korea. On the basis of nationwide delta variant surveillance, we divided the patients into two groups: 1) the delta-minor group (diagnosed from December 2020–June 2021, detection rate 90%). After propensity-score matching, the incidences of pneumonia, hospital transfer and need for supplemental oxygen were compared between the groups. In addition, risk factors for hospital transfer were analysed. @*Results@#A total of 1,915 patients were included. The incidence of pneumonia (14.6% vs.9.2%, P = 0.009), all-cause hospital transfer (10.4% vs. 6.3%, P = 0.020) and COVID-19-related hospital transfer (7.5% vs. 4.8%, P = 0.081) were higher in the delta-dominant group than those in the delta-minor group. In the multivariate analysis, the delta-dominant group was an independent risk factor for all-cause (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.16–3.13; P = 0.011) and COVID-19-related hospital transfer (aOR, 1.86; 95% CI, 1.04–3.32; P = 0.036). @*Conclusion@#Hospitalization rates were increased in the adult COVID-19 patients during the delta variant nationwide outbreak. Our results showed that the delta variant may be more virulent than previous lineages.

Impact of Molecular Drug Susceptibility Testing on the Time to Multidrug-resistant Tuberculosis Treatment Initiation

Background@#The purpose of this study was to evaluate the current status and trends in the coverage of molecular drug susceptibility testing (mDST), and the impact of mDST on the time to multidrug-resistant tuberculosis (MDR-TB) treatment initiation in Korea. @*Methods@#We included confirmed rifampin-resistant (RR)/MDR-TB patients who submitted application forms for novel drug uses to the National TB Expert Review Committee from September 1, 2016 to November 30, 2019. We retrospectively reviewed their medical records. @*Results@#Of the 621 MDR/RR-TB patients, mDST was performed in 442 (71.2%); Xpert MTB/ RIF (Xpert) alone in 109 (17.6%), MTBDRplus line probe assay (LPA) alone in 199 (32.0%), and both Xpert and LPA in 134 (21.6%) patients. The coverage rate of mDST has gradually increased to 70% in 2015, 50.7% in 2016, 67.9% in 2017, 75.2% in 2018, and 79.4% in 2019 (p for trend < 0.001). Median time to MDR-TB treatment initiation was 35 days (interquartile range 25–75 0–72), which has gradually decreased during the study period (p< 0.001).Independent predictors of shorter time to MDR-TB treatment initiation were retreatment case (adjusted hazard ratio [aHR], 1.30; 95% confidence interval [CI], 1.10–1.54), Xpert testing (aHR, 2.42; 95% CI, 2.03–2.88), and LPA testing (aHR, 1.83; 95% CI, 1.55–2.16).Transfer to another healthcare facility was inversely related to shorter time to treatment initiation (aHR, 0.74; 95% CI, 0.63–0.88). @*Conclusion@#mDST coverage is gradually increasing and contributes to reducing the time to MDR-TB treatment initiation. Further efforts are needed to achieve universal access to mDST and to properly integrate mDST into routine clinical practice.

Evaluation of Reverse Hybridization Assay for Detecting Fluoroquinolone and Kanamycin Resistance in Multidrug-Resistance Mycobacterium tuberculosis Clinical Isolates / 결핵및호흡기질환

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an increasing public health problem and poses a serious threat to global TB control. Fluoroquinolone (FQ) and aminoglycoside (AG) are essential anti-TB drugs for MDR-TB treatment. REBA MTB-FQ(R) and REBA MTB-KM(R) (M&D, Wonju, Korea) were evaluated for rapid detection of FQ and kanamycin (KM) resistance in MDR-TB clinical isolates. METHODS: M. tuberculosis (n=67) were isolated and cultured from the sputum samples of MDR-TB patients for extracting DNA of the bacilli. Mutations in genes, gyrA and rrs, that have been known to be associated with resistance to FQ and KM were analyzed using both REBA MTB-FQ(R) and REBA MTB-KM(R), respectively. The isolates were also utilized for a conventional phenotypic drug susceptibility test (DST) as the gold standard of FQ and KM resistance. The molecular and phenotypic DST results were compared. RESULTS: Sensitivity and specificity of REBA MTB-FQ(R) were 77 and 100%, respectively. Positive predictive value and negative predictive value of the assay were 100 and 95%, respectively, for FQ resistance. Sensitivity, specificity, positive predictive value and negative predictive value of REBA MTB-KM(R) for detecting KM resistance were 66%, 94%, 70%, and 95%, respectively. CONCLUSION: REBA MTB-FQ(R) and REBA MTB-KM(R) evaluated in this study showed excellent specificities as 100 and 94%, respectively. However, sensitivities of the assays were low. It is essential to increase sensitivity of the rapid drug resistance assays for appropriate MDR-TB treatment, suggesting further investigation to detect new or other mutation sites of the associated genes in M. tuberculosis is required.

Acquired Drug Resistance during Standardized Treatment with First-line Drugs in Patients with Multidrug-Resistant Tuberculosis / 결핵및호흡기질환

BACKGROUND: First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB. METHODS: This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively. RESULTS: Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found. CONCLUSION: First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.

Trend of Multidrug and Extensively Drug Resistant Tuberculosis in a Tuberculosis Referral Hospital, 2001~2005 / 결핵및호흡기질환

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) are serious threats to worldwide tuberculosis control, but the national burden and the trends of infectious spread are largely unknown. METHODS: We retrospectively reviewed the results of drug sensitivity tests and medical records of patients that were diagnosed with culture-confirmed pulmonary tuberculosis and were admitted to the National Masan Tuberculosis Hospital between 2001 and 2005. RESULTS: From 2001 to 2005, the proportion of MDR-TB among new cases was 9.2%, 13.8%, 16.9%, 23% and 27.0% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of MDR-TB among previously treated cases was 58.5%, 60.2%, 62.7%, 61.7% and 71.3% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for MDR-TB among both new and previously treated cases (p<0.001, p=0.002 for trend, respectively). The proportion of XDR-TB among new cases was 0%, 2.3%, 3.1%, 2.5% and 6.3% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of XDR-TB among previously treated cases was 9.1%, 15.7%, 17.3%, 19.9% and 19.1% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for XDR-TB among both new and previously treated cases (p=0.005, p<0.001 for trend, respectively). CONCLUSION: Both MDR-B and XDR-TB were gradually increased among both new and previously treated cases. Integrated national surveillance, including the public and private sectors, will be needed to estimate the exact status of antituberculous drug resistance.

Comparison of Smear and Culture Positivity using NaOH Method and NALC-NaOH Method for Sputum Treatment / 결핵및호흡기질환

BACKGROUND: Sputum decontamination with NALC-NaOH (N-acetyl-L-cysteine-sodium hydroxide) is known to better detect Mycobacterium tuberculosis (M. tb) by culture than that with using NaOH, which is widely used in Korean hospitals. In this report, sputum samples collected from pulmonary tuberculosis (TB) patients were treated with either NaOH or NALC-NaOH, and we compared the results of smear and culture positivity to determine whether the NALC-NaOH treatment method improves culture positivity in the sputum samples, and especially for those sputum samples that are smear negative and scanty. METHODS: For each decontamination method, 436 sputum samples from pulmonary TB patients in the National Masan Tuberculosis Hospital were collected for this study. Sputum from a patient was collected two times for the first and second day of sampling time, and these samples were employed for the decontamination process by performing the 4% NaOH and NALC-2% NaOH treatment methods, respectively, for detecting M. tb by an AFB (Acid Fast Bacilli) smear and also by culture in solid Ogawa medium. RESULTS: The NaOH and NALC-NaOH treatment methods did not significantly affect the AFB smear positivity of the sputum samples (33.0% vs 39.0%, respectively, p=0.078). However, the culture positive percents of M. tb in the Ogawa medium treated with NALC-NaOH and NaOH were 39.7% and 28.0%, respectively, which was a significantly different (p=0.0003). This difference in culture was more prominent in the sputum samples that were smear negative (the positive percents with NALC-NaOH and NaOH were 15.8% and 7.2%, respectively, p=0.0017) and scanty (NALC-NaOH and NaOH were 60.8% and 42.9%, respectively, p=0.036), but not for a smear that was 1+ or higher (p>0.05). CONCLUSION: NALC-NaOH treatment is better than NaOH treatment for the detection of M. tb by culture, but not by smear, and especially when the AFB smear is negative and scanty.