Trend of multidrug and fluoroquinolone resistance in Mycobacterium tuberculosis isolates from 2010 to 2014 in Korea: a multicenter study

BACKGROUND/AIMS@#This study was conducted to evaluate the recent prevalence and trend of anti-tuberculosis (TB) drug resistance with a focus on multidrug-resistance (MDR) and fluoroquinolone resistance in South Korea.@*METHODS@#We retrospectively reviewed the drug susceptibility testing results of culture-confirmed Mycobacterium tuberculosis isolates collected from 2010 to 2014 at seven tertiary hospitals in South Korea.@*RESULTS@#A total of 5,599 cases were included: 4,927 (88.0%) were new cases and 672 (12.0%) were previously treated cases. The MDR rate has significantly decreased from 6.0% in 2010 to 3.0% in 2014 among new cases, and from 28.6% in 2010 to 18.4% in 2014 among previously treated cases (p < 0.001 and p = 0.027, respectively). The resistance rate to any fluoroquinolone was 0.8% (43/5,221) in non-MDR-TB patients, as compared to 26.2% (99/378) in MDR-TB patients (p < 0.001). There was no significant change in the trend of fluoroquinolone resistance among both nonMDR-TB and MDR-TB patients. Among the 43 non-MDR-TB patients with fluoroquinolone resistance, 38 (88.4%) had fluoroquinolone mono-resistant isolates.@*CONCLUSIONS@#The prevalence of MDR-TB has significantly decreased from 2010 to 2014. The prevalence of fluoroquinolone resistance among non-MDR-TB patients was low, but the existence of fluoroquinolone mono-resistant TB may be a warning on the widespread use of fluoroquinolone in the community.

Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design

Detailed information on additional drug resistance patterns of multidrug-resistant tuberculosis (MDR-TB) is essential to build an effective treatment regimen; however, such data are scarce in Korea. We retrospectively analyzed the results of phenotypic drug susceptibility testing (DST) of culture confirmed-TB patients from January 2010 to December 2014 in 7 university hospitals in Korea. MDR-TB was identified among 6.8% (n = 378) of 5,599 isolates. A total of 57.1% (n = 216) of the MDR-TB patients had never been treated for TB. Strains from MDR-TB patients showed additional resistance to pyrazinamide (PZA) (35.7%), any second-line injectable drug (19.3%), and any fluoroquinolone (26.2%). Extensively drug resistant TB comprised 12.4% (n = 47) of the MDR-TB patients. Of 378 MDR-TB patients, 50.3% (n = 190) were eligible for the shorter MDR-TB regimen, and 50.0% (n = 189) were fully susceptible to the 5 drugs comprising the standard conventional regimen (PZA, kanamycin, ofloxoacin, prothionamide, and cycloserine). In conclusion, the proportion of new patients and the levels of additional drug resistance were high in MDR-TB patients. Considering the high levels of drug resistance, the shorter MDR-TB treatment regimen may not be feasible; instead, an individually tailored regimen based on the results of molecular and phenotypic DST may be more appropriate in MDR-TB patients in Korea.

The Prognostic Value of the Charlson's Comorbidity Index in Patients with Prolonged Acute Mechanical Ventilation: A Single Center Experience / 결핵및호흡기질환

BACKGROUND: The aim of our study was to evaluate the prognostic value of Charlson's weighted index of comorbidities (WIC) in patients with prolonged acute mechanical ventilation (PAMV, ventilator care ≥96 hours). METHODS: We retrospectively enrolled 299 Korean PAMV patients who were admitted in a medical intensive care unit (ICU) of a university-affiliated tertiary care hospital between 2008 and 2013. Survivors were defined as patients who survived for 60 days after ICU admission. RESULTS: The patients' mean age was 65.1±14.1 years and 70.6% were male. The mean ICU and hospital length of stay was 21.9±19.7 and 39.4±39.1 days, respectively. In addition, the 60-day mortality rate after ICU admission was 35.5%. The mean WIC was 2.3±1.8, with significant differences between nonsurvivors and survivors (2.7±2.1 vs. 2.1±1.7, p<0.05). The area under the curve of receiver-operating-characteristics curve for WIC was 0.593 (95% confidence interval [CI], 0.523–0.661; p<0.05). Based on Kaplan-Meier curves of 60-day survival, WIC ≥5 had statistically lower survival than WIC <5 (log-rank test, p<0.05). In a multivariate Cox proportional hazard model, WIC ≥5 was associated with poor prognosis (hazard ratio, 1.901; 95% CI, 1.140–3.171; p<0.05). The mortality rate of patients with WIC ≥5 was 54.2%. CONCLUSION: Our study showed a WIC score ≥5 might be helpful in predicting 60-day mortality in PAMV patients.

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.

Diagnosis and Treatment of Latent Tuberculosis Infection in Healthcare Workers / 결핵및호흡기질환

Tuberculosis (TB) is one of the most important occupational risks for healthcare workers (HCWs) in South Korea. Many policies regarding the control and prevention of TB in healthcare settings recommend that HCWs are tested for latent tuberculosis infection (LTBI) in addition to active TB. Moreover, the Korean Tuberculosis Prevention Act also recommends that HCWs receive regular testing for LTBI. However, there are no specific or detailed guidelines for dealing with LTBI in HCWs. Herein, we discuss the diagnosis and treatment of LTBI in HCWs and focus particularly on the baseline screening of hired HCWs, routine follow-up, and contact investigation.

Predictors of Recurrence after Curative Resection in Patients with Early-Stage Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: There have been various results from studies concerning the predictors of recurrence in early-stage nonsmall cell lung cancer (NSCLC). Therefore, an accurate assessment is needed to guide effective adjuvant therapy. We investigated the predictors of a recurrence in patients with resected, early-stage NSCLC and the risk factors associated with locoregional or distant recurrence. METHODS: This retrospective study was conducted on patients at the Pusan National University Hospital from January 2006 to December 2011. Patients with pathological stages I or II were included in this study, as based on the seventh edition TNM staging system. Multivariate Cox proportional hazard models were used to identify factors associated with recurrence. RESULTS: Two hundred and forty-nine patients were included. Among them, 180 patients were stage I, and 69 were stage II. Overall, by multivariate analysis, the independent factors associated with a 5-year total recurrence were the presence of visceral pleural invasion (VPI) (p=0.018) and maximal standardized uptake values (SUVs) of tumors on positron emission tomography (PET) >4.5 (p=0.037). The VPI was the only independent risk factor associated with both locoregional and distant recurrence, in the analysis of the patterns of tumor recurrence and their risk factors. In the subgroup analysis of stage I patients, three variables (male, VPI and resection margin positive) were significantly associated with a 5-year recurrence. CONCLUSION: The independent factors associated with postoperative recurrence in early-stage NSCLC were as follows: PET SUV >4.5 and the presence of VPI. For patients with those factors adjuvant therapy should be recommended as a more efficacious treatment.

The Current Status of Medical Decision-Making for Dying Patients in a Medical Intensive Care Unit: A Single-Center Study / 대한구급학회지

BACKGROUND: Many terminally ill patients die while receiving life-sustaining treatment. Recently, the discussion of life-sustaining treatment in intensive care units (ICUs) has increased. This study is aimed to evaluate the current status of medical decision-making for dying patients. METHODS: The medical records of patients who had died in the medical ICU from March 2011 to February 2012 were reviewed retrospectively. RESULTS: Eighty-nine patients were enrolled. Their mean age was 65.8 +/- 13.3 years and 73.0% were male. The most common diagnosis was acute respiratory failure, and the most common comorbidity was hemato-oncologic malignancy. Withdrawing or withholding life-sustaining treatment including do-not-resuscitate (DNR) orders was discussed for 64 (71.9%) patients. In almost all cases, the discussion involved a physician and the patient's family. No patient wrote advance directives themselves before ICU admission. Of the patients for whom withdrawing or withholding life-sustaining treatment was discussed, the decisions were recorded in formal consent documents in 36 (56.3%) cases, while 28 (43.7%) cases involved verbal consent. In patients granting verbal consent, death within one day of the consent was more common than in those with formal document consent (85.7% vs. 61.1%, p < 0.05). The most common demand was a DNR order. Patients died 2.7 +/- 1.0 days after the decision for removal of life-sustaining treatment. CONCLUSIONS: The decision-making for life-sustaining treatment of dying patients in the ICU very often involves conflict. There is a general need to heighten our sensitivity on the objective decision-making based on patient autonomy.

Characteristics of depression and anxiety in elderly asthmatics

PURPOSE: The prevalence of asthma among the elderly has increased in the aging society. However, limited studies have been conducted regarding the characteristics of elderly asthmatics. In this study, we aimed to evaluate control of asthma, comorbidities, depression and anxiety state, and quality of life in elderly asthmatics. METHODS: A total of 281 patients who were diagnosed with asthma and treated more than 1 year were enrolled. We evaluated not only clinical characteristics, but also depression, anxiety, and quality of life by using the Beck Depression Inventory-Korean version (K-BDI), the State-Trait Anxiety Inventory, and Korean asthma quality of life (KAQLQ), respectively. RESULTS: Diabetes mellitus (15.2% vs. 6.6%, P=0.020), hypertension (45.5% vs. 18.7%, P<0.001), and heart disease (18.2% vs. 6.0%, P=0.001) were more prevalent comorbidities in elderly asthmatics than young asthmatics. However, there were no differences in the degree of asthma control and lung function between elderly and young asthmatics. K-BDI scores were higher (12.32 vs. 10.99, P=0.020) and KAQLQ was lower (66.60 vs. 68.83, P=0.046) in the elderly asthmatics than in the young asthmatics. Moreover, the low score of asthma control test was significantly associated with depression in the elderly asthmatics (P=0.01). CONCLUSION: Elderly asthmatics had a higher degree of depression and a lower quality of life. Inadequate control of asthma was associated with depression. To achieve adequate control of asthma, it would be necessary to assess depression in the elderly asthmatics.

Metabolic Burden Measured by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Is a Prognostic Factor in Patients with Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Evidence regarding the usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting the prognosis of non-small cell lung cancer is increasing. However, data on small cell lung cancer (SCLC) are scarce. The aim of this study was to evaluate the prognostic value of metabolic parameters measured using 18F-FDG PET/CT in patients with SCLC. MATERIALS AND METHODS: We conducted a retrospective review of 114 patients with pathologically proven SCLC (26 cases of limited disease and 88 cases of extensive disease) who underwent pretreatment 18F-FDG PET/CT. The maximal SUV (SUVmax) was used quantitatively for determination of FDG PET activity. The SUVmax of the primary tumor (primary SUVmax), the sum of SUVmax values of malignant lesions (SUVsum), and the mean SUVmax of malignant lesions were calculated. RESULTS: The patient population was subdivided using a median SUVsum value of 24.6. High SUVsum showed a significant association with known factors for poor prognosis, including higher neuron-specific enolase (p=0.010), CYFRA 21-1 (p=0.014), and extensive disease status (p=0.007). Patients with high SUVsum had significantly shorter median overall survival (6.6 months vs. 13.0 months, p<0.001) and progression-free survival (5.2 months vs. 8.0 months, p<0.001) than patients with low SUVsum. Results of multivariate analysis showed that SUVsum, chemotherapy cycles, and the response to first-line treatment were significant prognostic factors of survival. In contrast, mean SUVmax and primary SUVmax were not significant predictors of survival. CONCLUSION: In this study, metabolic burden represented by SUVsum from pretreatment 18F-FDG PET/CT was an independent prognostic factor in patients with SCLC.

Clinical Characteristics in Patients with Carbapenem-Resistant Acinetobacter baumannii Isolates from Tracheal Secretions / 대한구급학회지

BACKGROUND: This study was conducted to evaluate the clinical characteristics and outcomes of mechanically ventilated patients with carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from tracheal secretions in a medical intensive care unit (ICU) of a university hospital. METHODS: We conducted a retrospective study from January 2009 to June 2012. RESULTS: Among the patients who had isolates cultured from tracheal secretions, 130 patients (34.8%) had CRAB isolates. Their mean age was 65 +/- 14 yr and 74.6% were male. The ICU and hospital mortality was 51.5% and 60.0%, respectively. According to physician's clinical decision, antibiotics were changed in order to cover CRAB in 75 (57.7%) patients. The total duration of antibiotics use was 12.2 +/- 8.1 days. Of patients with antibiotics change to cover CRAB, 70 patients (93.3%) had Clinical Pulmonary Infection Score of 6 and over. However, there was no significant difference in hospital mortality between patients with antibiotics change against CRAB and those without change. In multivariable analysis, only Acute Physiology and Chronic Health Evaluation II score was related to hospital mortality of patients with CRAB. CONCLUSIONS: In this study, changing antibiotics to cover CRAB by physician's clinical decision only did not influence hospital mortality; further studies would be necessary to investigate how to use antibiotics against CRAB isolates cultured from tracheal secretions.

Successful desensitization for vancomycin hypersensitivity

Vancomycin frequently induces hypersensitivity reactions including red man syndrome (RMS) and anaphylaxis. Lowering infusion rate with antihistamine premedication is usually effective to reduce RMS, however, desensitization should be considered for severe reactions not responding to usual measures. Here, we report a case of a patient with pyogenic spondylitis who had developed hypersensitivity reaction to vancomycin, got a full recovery with vancomycin desensitization. A 63-year-old man was transferred to our hospital for back pain, proved to pyogenic spondylitis. As methicillin-resistant Staphylococci aureus infection was suspected, vancomycin was administrated. But, he showed hypersensitivity reactions such as hypotension, dyspnea and severe flushing after vancomycin administration at previous hospital. Readministration of vancomycin at a lower infusion rate with premedication was tried. Three hours after vancomycin infusion, he developed fever, chills, rash and hypotension. Thrombocytopenia was occurred after administration of other antibiotics including cefazolin and teicoplanin. Vancomycin administration was attempted according to a rapid desensitization protocol. The infusion rate of vancomycin was increased to the standard rate. After the desensitization, he successfully completed the full course of treatment with vancomycin. Vancomycin desensitization could be the option for the vancomycin hypersensitivity when other antibiotics are not feasible.

Usefulness of Plasma Procalcitonin to Predict Severity in Elderly Patients with Community-Acquired Pneumonia / 결핵및호흡기질환

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading causes of death among the elderly. Several studies have reported the clinical usefulness of serum procalcitonin, a biomarker of bacterial infection. However, the association between the levels of procalcitonin and the severity in the elderly with CAP has not yet been reported. The aim of this study was to evaluate usefulness of procalcitonin as a predictor of severity and mortality in the elderly with CAP. METHODS: This study covers 155 CAP cases admitted to Pusan National University Hospital between January 2010 and December 2010. Patients were divided into two groups (> or =65 years, n=99; <65 years, n=56) and were measured for procalcitonin, C-reactive protein (CRP), white blood cell, confusion, uremia, respiratory rate, blood pressure, 65 years or older (CURB-65) and pneumonia severity of index (PSI). RESULTS: The levels of procalcitonin were significantly correlated with the CURB-65, PSI in totals. Especially stronger correlation was observed between the levels of procalcitonin and CURB-65 in the elderly (procalcitonin and CURB-65, rho=0.408 with p<0.001; procalcitonin and PSI, rho=0.293 with p=0.003; procalcitonin and mortality, rho=0.229 with p=0.023). The correlation between the levels of CRP or WBC and CAP severity was low. The existing cut-off value of procalcitonin was correlated with mortality rate, however, it was not correlated with mortality within the elderly. CONCLUSION: The levels of procalcitonin are more useful than the levels of CRP or WBC to predict the severity of CAP. However, there was no association between the levels of procalcitonin and mortality in the elderly.

Association between Bone Marrow Hypermetabolism on (18)F-Fluorodeoxyglucose Positron Emission Tomography and Response to Chemotherapy in Non-Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: (18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is widely used for the diagnosis and staging of non-small cell lung cancer (NSCLC). The aim of this study is to determine whether the bone marrow hypermetabolism seen on FDG-PET predicts a response to chemotherapy in patients with NSCLC. METHODS: We evaluated the patients with advanced NSCLC and who were treated with combination chemotherapy. For determination of the standardized uptake value (SUV) of the bone marrow (BM SUV) on FDG-PET, regions of interest (ROIs) were manually drawn over the lumbar vertebrae (L1, 2, 3). ROIs were also drawn on a homogenous transaxial slice of the liver to obtain the bone marrow/ liver SUV ratio (BM/L SUV ratio). The response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumor (RECIST) criteria after three cycles of chemotherapy. RESULTS: Fifty-nine NSCLC patients were included in the study. Multivariate analysis was performed using a logistic regression model. The BM SUV and the BM/L SUV ratio on FDG-PET were not associated with a response to chemotherapy in NSCLC patients (p=0.142 and 0.978, respectively). CONCLUSION: The bone marrow hypermetabolism seen on FDG-PET can not predict a response to chemotherapy in NSCLC patients.

Spontaneous regression of neointimal hyperplasia in a patient who underwent percutaneous coronary intervention with a bare metal stent / 대한내과학회지

Many interventional cardiologists rely upon percutaneous coronary intervention (PCI) with drug-eluting stents (DES), but DES may provoke serious complications, such as stent thrombosis and delayed restenosis. Previous studies of bare metal stent placement showed regression of neointimal proliferation after 6 months. Here, we report the case of a 50-year-old man demonstrating spontaneous regression of neointimal hyperplasia after undergoing PCI with a bare metal stent to treat a middle left anterior descending (LAD) artery lesion. Coronary angiography showed 90% diffuse restenosis at 6 months after stent placement, but the patient refused PCI due to monetary concerns. After 29 months, follow-up angiography revealed spontaneous regression of restenosis in the middle LAD.

Clinical Features of Thymic Epithelial Tumors / 결핵및호흡기질환

BACKGROUND: Thymic epithelial tumors are the most common tumors affecting the anterior mediastinum. The aim of this study is to investigate clinical features of the patients who were diagnosed with thymic epithelial tumors at Pusan National University Hospital. METHODS: We retrospectively reviewed the records of thirty-seven patients who were diagnosed with thymic epithelial tumors from Jan. 1997 to Jan. 2007. The pathological classification and clinical stage of the thymic epithelial tumors were based on the WHO classification and Masaoka's staging system. A total 37 patients were enrolled: 23 were males and 14 were females, and their mean age was 51.3 years. RESULTS: Thirty patients presented symptoms at the time of diagnosis and their symptoms were as follows: chest pain (53%), dyspnea (23%), and cough (17%). Myasthenia gravis was diagnosed in five patients. With respect to the tumor staging, three cases (8%) were stage I, 10 cases (28%) were stage II, 12 cases (32%) were stage III, 6 cases (16%) were stage IVA and 6 cases (16%) were stage IVB. Twenty-four cases (67%) displayed stage III or IV disease. The pathological types according to the WHO classification were as follows: B1 (32%), C (23%), B3 (20%), B2 (16%), AB (6%) and A (3%). Twenty-four patients underwent thymothymectomy and four of these patients relapsed. Stage III or type B3 was common in the relapsed patients. Five patientsexpired. Stage IV or type B3 and C were common in the expired patients. CONCLUSION: In this study, stage III or IV disease and type B3 or C were common at the time of diagnosis and these findings might contribute to postoperative recurrence and a poor outcome.