• Korean Journal of Soil Science and Fertilizer
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• v.40 no.1
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• pp.43-50
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• 2007

Veterinary antibiotics have been widely used to increase feed efficiency, to prevent disease, and to promote growth as well as to control disease. The antibiotics administered can be excreted through the urine and feces. One of the major routes of veterinary antibiotics entering soil and water environment is via the application of animal manure to agricultural land as an organic fertilizer source. Since little is known about impacts of antibiotics on the environment, this study was conducted to prioritize the veterinary antibiotics based on the consumption and potential to reach the environment. Among 83 veterinary antibiotics consumed in Korea, ten antibiotics were used at the greater dose than 25 Mg in 2004. Potential to reach the environment was determined according to excretion rate after administered to animals and sorption affinity to soil solids after applied to agricultural land. Seventeen antibiotic active ingredients (Ais) were classified as 'High' priority in terms of the potential to reach the environment. An overall priority score was determined by combining priority score based on consumption with the degree of potential environment exposure. Twenty veterinary antibiotic AIs were classified as 'Very high' or 'High' priority requiring detailed assessment. The antibiotic AIs were identified four aminoglycosides, two macrolides, two penicillins, five sulfonamides, three tetracyclines, two quinolones, and two miscellaneous. Eight veterinary antibiotic AIs including amoxicillin, carbadox, chlortetracycline, neomycin, oxytetracycline, sulfamethazine, sulfathiazole, and tylosin were identified to have a greater priority of environmental risk in Korea.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1072-1082
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• 1997

Background : To characterize the clinical features and determine the prognostic factors of severe community-acquired pneumonia. This study is the first of its kind in Korea. Methods : Recruited were 40 patients diagnosed as severe community-acquired pneumonia in Hallym University Hospital from January 1, 1989 through July 31, 1996. Patients were analysed retrospectively for age, sex, underlying disease, respiration rate, hypoxemia, requirement of mechanical ventilation, involvement on chest radiograph, shock, and the serum concentration of BUN and albumin. All parameters were compared between survived and dead group. Results : Male to female ratio was 2.07 : 1. The mean age was $63.1{\pm}17.5$years(range 25~90years) with 65% of patients aged equal to or more than 60. The major underlying diseases were old pulmonary tuberculosis(12.5%), chronic obstructive pulmonary disease(7.5%), bronchial asthma(5%), bronchiectasis(2.5%), and diabetes mellitus(22.5%). Microbiologic diagnosis was made in 26 out of 40 patients(65%). The most common causative organism was S. pneumoniae(17.5%, 7/40) followed by S. aureus(15.0%, 6/40), K. Pneumoniae(12.5%, 5/40), M. tuberculosis(7.5%, 3/40), H. influenzae(2.5%, 1/40), coagulase negative staphylococcus(2.5%, 1/40), P. aeruginosa(2.5%. 1/40), E. cloaceae(2.5%, 1/40), and E. coli(2.5%, 1/40). M. pneumoniae was detected in no patient. The most frequent drugs administered in single or combination therapy were aminoglycosides(75%, 30/40), second- and third-generation cephalosporin(40%, 16/40 and 27.5%, 11/40), macrolides(27.5%, 11/40), and amoxicillin/clavulanic acid(22.5%, 9/40). Of the 40 patients, 14 died of severe community-acquired pneumonia(37.5%). Among them, seven patients (50%) expired within 72h of hospital arrival. According to multivariate analysis, mortality was significantly associated with requirement of mechanical ventilation, bilateral pulmonary involvement, and serum albumins$\leq$3.0g/dl. Conclusion : An understanding of the clinical characteristics and prognostic factors in severe community-acquired pneumonia identified in this study will optimize therapeutic approach in this disease and help decreasing its notorious mortality rate.

• Tuberculosis and Respiratory Diseases
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• v.58 no.3
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• pp.257-266
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• 2005

Background : The study of pneumonia among young men living in a group is rare. prospective study was conducted to determine the etiology, and compare the effects of macrolide and second-generation cephalosporin on the treatment of pneumonia among combat policemen. Patients and Methods : From January 2003 to April 2004, Fifty-two patients with pneumonia were treated with either azithromycin(n=25) or cefuroxime(n=27). In order to determine the cause of the pneumonia, culture studies and serologic tests for antibodies to Mycoplasma pneumoniae and Chlamydia pneumoniae were carried out. During the two weeks of medication, the Chest X-rays, blood tests and culture studies(if necessary) were followed weekly. A serologic study was followed at the end of the second week. Results : The main pathogens for pneumonia among combat policemen were Mycoplasma pneumoniae(50.0%), Chlamydia pneumoniae(10.8%), and Streptococcus pneumoniae(3.8%). The treatment was successful in most cases(51/52 cases, 98.1%). The effects of azithromycin and cefuroxime were similar (96.0% vs 100%, p>0.05). In one patient who had taken azithromycin, the clinical and radiological findings did not improved until intravenous second generation ce phalosporin had been infused. Conclusion : Atypical pathogens were the main causes of the pneumonia in the combat policemen, and the effects of macrolide and second generation cephalosporin for pneumonia were similar. However, further studies will be needed to determine if single therapy with macrolide is possible.

• Korean Journal of Food Science and Technology
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• v.42 no.3
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• pp.287-291
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• 2010

In this study, a simple and rapid pre-treatment method based on liquid extraction was applied for the simultaneous determination of three macrolides (spiramycin, tylosin, and tilmicosin) residues. In these studies, the stock farm products was used as a matrix sample. When the liquid extraction method was compared with the solid phase extraction (SPE) method, the former showed higher recovery percentages and simpler steps than the latter. The macrolids were separated using a reverse-phase C18 ($250\;mm{\times}4.6\;mm$, $5\;{\mu}m$) column and a gradient elution with mobile phases consisting of phosphate buffer (pH 2.5) and acetonitrile. Tylosin and tilmicosin were detected at 288 nm and spiramycin was detected at 232 nm. The average recovery percentage ranged between 83.0-90.2% for samples spiked with the three macrolids at 50 and 100 ng/g The validation results showed that the limit of detection (7 (spiramycin), 12 (tilmiconsin), 12 (tylosin) ng/g)) was under the regulatory tolerances and the linearity from calibration curves was satisfactory for determining the multi-residue of three macrolids in farm products. Monitoring samples were collected at the main cities in Korea as Seoul, Busan, Deajeon, Incheon, Deagu, and Gwangju. Microlide antibiotics were not detected in most samples.

• Tuberculosis and Respiratory Diseases
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• v.66 no.5
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• pp.358-364
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• 2009

Background: The appropriate empirical antimicrobial choice in the treatment of community-acquired pneumonia (CAP) should be advocated by community-based information on the etiologic pathogens, their susceptibility to antimicrobials, clinical characteristics and outcomes. Jeju is a geographically isolated and identical region in Korea. However, there is no regional reference on adult CAP available. This study investigated the etiologic agents and clinical outcomes of adult patients diagnosed with CAP in Jeju, Korea, to help guide the empirical antimicrobial choice. Methods: A prospective observational study for one year in a referral hospital in Jeju, Korea. Patients diagnosed with CAP were enrolled with their clinical characteristics. Microbiological evaluations to identify the etiologic agents in the adult patients with CAP were performed with blood culture, expectorated sputum smear and culture, antibody tests for mycoplasma, chlamydophila, and antigen tests for legionella and pneumococcus. The clinical outcomes of the initial empirical treatment were analyzed. Results: Two hundred and three patients with mean age of 64 and 79 females were enrolled. Ten microbials from 90 cases (44.3%) were isolated and multiple isolates were confirmed in 30. Among the microbial isolates, S. pneumoniae (36.3%) was the most common, followed by M. pneumoniae (23.0%), C. pneumoniae (17.0%), S. aureus (9.6%) and P. aeruginosa (5.9%). The initial treatment failure (23.8%) was related to the isolation of polymicrobial pathogens, elevated inflammatory markers, and the presence of pleural effusion. Among the 30 isolates of S. pneumoniae, 16 (53.3%) were not susceptible to penicillin, and 19 isolates (63.3%) to erythromycin and clarithromycin. However, 29 isolates (96.7%) were susceptible to levofloxacin and ceftriaxone. Conclusion: S. pneumoniae, M. pneumoniae, S. aureus, and P. aeruginosa are frequent etiologic agents of adult CAP in Jeju, Korea. The clinical characteristics and antibiotic resistance should be considered when determining the initial empirical antimicrobial choice. Respiratory quinolone or ceftriaxone is recommended as an empirical antimicrobiotic in the treatment of adult CAP in Jeju, Korea.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.184-189
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• 2010

Purpose : Pseudomembranous colitis (PMC) occurs rarely in children, but its incidences are increasing due to frequent antibiotic use. We investigated the incidence and clinical characteristics of PMC accompanied by bacterial enteritis-like symptoms in children. Methods : Between November 2003 and July 2007 at the Department of Pediatrics, Dongsan Medical Center, we analyzed the medical records of consecutive patients who received antibiotics in the past 1 month, developed bacterial enteritis-like symptoms, and were diagnosed with PMC based on sigmoidoscopy examination and histological findings. Results : Among 22 patients who underwent sigmoidoscopy and biopsy examinations, 11 (50%) were diagnosed with PMC. These 11 patients were aged 2 months-12 years, among whom 5 patients (45.5%) were less than 1 year old. The clinical symptoms were bloody diarrhea (28.6%), abdominal pain or colic (28.6%), watery or mucoid diarrhea (23.8%), vomiting (9.5%), and fever (9.5%). The antibiotics used were penicillins (55.6%), macrolides (27.8%), cephalosporins (11.1%), and aminoglycosides (5.6%). The period of antibiotic use was 3-14 days. The interval between the initial antibiotic exposure and the onset of symptoms was 5-21 days. The results of stool examination of all patients were negative for Clostridium difficile toxin A. Patient distribution according to the degree of PMC was as follows: grade I, 18.2% (2 cases); grade II, 27.3% (3); grade III, 36.4% (4); and grade IV, 18.2% (2). PMC did not recur in any case.Conclusion : PMC is not a rare disease in children. If pediatric patients receiving antibiotics manifest symptoms like bacterial enteritis, PMC should be suspected. Endoscopy and biopsy should be applied as aggressive diagnostic approaches to detect this condition.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.178-183
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• 2010

Purpose : The aim of this study was to identify mutations associated with macrolide resistance in Mycoplasma pneumoniae (MP) and to establish a cultural method to determine antimicrobial susceptibility. Methods : Nasopharyngeal aspirates (NPAs) were collected from 62 children diagnosed with MP pneumonia by a serologic method or polymerase chain reaction. The 23S rRNA and L4 ribosomal protein genes of MP were amplified and sequenced. To identify mutations in these 2 genes, their nucleotide sequences were compared to those of the reference strain M129. MP cultivation was carried out for 32 (28 frozen and 5 refrigerated) NPAs and M129 strain using Chanock's glucose broth and agar plate in a 5% $CO_2$ incubator at $37^{\circ}C$ and examined at 2-3 day intervals for 6 weeks. Results : Among the 62 specimens, 17 had M144V mutations in ribosomal protein L4. The A2064G mutation was observed in 1 specimen; its 23S rRNA gene was successfully sequenced. Culture for MP was successful from the M129 strain and 2 of the 5 NPAs that were refrigerated for no longer than 3 days. However, MP did not grow from the 28 NPAs that were kept frozen at $-80^{\circ}C$ since 2003. Conclusion : We found the M144V mutation of L4 protein to be common and that of domain V of 23S rRNA gene was relatively rare among MP. Studies on the prevalence of macrolide-resistant MP and the relationship between the mutations of 23S rRNA gene and ribosomal protein L4 will aid in understanding the mechanism of macrolide resistance in MP.

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.479-485
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• 2005

The 994 throat swabs obtained from 688 adults and 306 children patients with respiratory diseases were examined for Mycoplasma pneumoniae infection by culture method. Antimicrobial susceptibilities of the resulting 123 M. pneumoniae isolates were evaluated by testing minimum inhibitory concentrations (MICs) of erythromycin, minocycline, tetracycline, josamycin, sparfloxacin, ofloxacin, and ciprofloxacin by a broth micro-dilution method. The erythromycin resistant strains of M. pneumoniae was determined above $1.0{\mu}g/ml$ of MIC for erythromycin. The erythromycin resistant strains of M. pneumoniae was confirmed resistant gene mutation of the portions of genes 23S rRNA (domain II and V), and ribosomal protein 14 and L22 by PCR amplified and their nucleotide sequenses were compared to those of the susceptible strain M129. The isolation rate of M. pneumoniae was $12.9\%$ (89/688) for the adults and $11.1\%$ (34/306) for the children. The $MICs_{90}$ of the M. pneumoniae isolates were $0.12{\mu}g/ml$ for minocycline, $0.25{\mu}g/ml$ for sparfloxacin, $0.5{\mu}g/ml$ for ciprofloxacin, ofloxacin, and tetracycline, respectively, and $2.0{\mu}g/ml$ for josamycin and erythromycin, respectively. The isolation rate of erythromycin resistant M. pneumoniae from patients was $49.4\%\;(44/89)$ for the adults, $47.1\%\;(16/34)$ for children, and $48.8\%\;(60/123)$ for the total. No mutation could be detected in the ribosomal protein L22 region, but all strains were mutated in the ribosomal protein L4 as two point mutation M144V. Two point mutations in domain V of 23S rRNA were selected in the presense of erythromycin resistant M. pneumoniae isolates, such as one strain was G2057C mutant, two strains were A2059C mutants, three strains were C2611G mutants, four strains were A2058C mutants, five strains were A2058T mutants, twenty strains were A2059G mutants, and twenty-five strains were A2058G mutants, respectively. These results show that erythromycin was not the most active compound against M. pneumoniae infection in Korea and clinical studies of macrolides in human patients are demanded.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.37-45
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• 2024

Purpose: This study aimed to examine the clinical features and determinants of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMP) and to assess the differences in the time to fever resolution between doxycycline (DXC), tosufloxacin (TFX) and corticosteroid (CST) as second-line treatment. Methods: We retrospectively analyzed the medical records of patients under the age of 18 who were admitted to Nowon Eulji University Hospital between July 2018 and February 2020, diagnosed with mycoplasma pneumonia. Macrolide resistance was confirmed by detecting point mutations in the 23S rRNA gene. MUMP was clinically defined by persistent fever (≥38.0℃) lasting for 72 hours or more after the initiation of macrolide treatment. In cases of MUMP, patients were treated with an addition of CST, or the initial macrolide was replaced either DXC or TFX. Results: Out of 157 cases of mycoplasma pneumonia, 83 cases (52.9%) did not respond to macrolides. Patients with MUMP exhibited significantly higher C-reactive protein (CRP) levels (3.2±3.0 vs. 2.4±2.2 mg/dL, P=0.047), more frequent lobar/segmental infiltrations or pleural effusions (56.6% vs. 27.0%, P<0.001; 6.0% vs. 0.0%, P=0.032), and a higher prevalence of 23S rRNA gene mutations (96.4% vs. 64.6%, P<0.001) when compared to those with macrolide-susceptible M. pneumoniae pneumonia. In terms of second-line treatment, 15 patients (18.1%) responded to CST, 30 (36.1%) to DXC, and 38 (45.8%) to TFX. The time to defervescence (TTD) after initiation second-line treatment was significantly shorter in the CST group compared to the DXC (10.3±12.7 vs. 19.4±17.2 hours, P=0.003) and TFX groups (10.3±12.7 vs. 25.0±20.1 hours, P=0.043), with no significant difference observed between the DXC and TFX groups (19.4±17.2 vs. 25.0±20.1 hours, P=0.262). Conclusions: High CRP levels, the presence of positive 23S rRNA gene mutation, lobar or segmental lung infiltration, and pleural effusion observed in chest X-ray findings were significant factors associated with macrolide unresponsiveness. In this study, CST demonstrated a shorter TTD compared to DXC or TFX. Further, larger-scale prospective studies are needed to determine the optimal second-line treatment for MUMP.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.69-87
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• 2003

Background : LB20304(gemifloxacin) is a new fluoroquinolone antibacterial agent with excellent activity against both Gram-negative and Gram-positive organisms. In vitro studies using clinical isolates have shown gemifloxacin to be highly active against penicillin-resistant strains of S. pneumoniae and in contrast to other reference quinolones, gemifloxacin retained good activity against clinical isolates of S. pneumoniae that were resistant to other members of the quinolone class. Therefore, gemifloxacin is thought to be effective in treating acute bacterial exacerbation of chronic bronchitis(AECB). The objective of this study was to evaluate the efficacy and safety of oral gemifloxacin at doses of 160mg or 320mg once daily for 7 days for the treatment of AECB in Korean adult population. Methods : This was a randomized, multicenter, double-blind, parallel group Phase II study to assess the clinical and antibacterial efficacy and safety of oral gemifloxacin for the treatment of AECB. Treatment Group A (67 patients) took oral gemifloxacin 160mg once daily for seven days and treatment Group B (70 patients) took oral gemifloxacin 320mg once daily for seven days. Results : The demographic profiles of the two treatment groups were similar. The clinical response at follow-up was 84.2% in the gemifloxacin 160-mg group, and 88.7% in the gemifloxacin-320 mg group, showing no statistically significant difference between two treatment groups(p=0.49). The clinical response at the end of therapy was 96.5% in the 160-mg group, and 96.4% in the 320-mg group. The bacteriological response at the end of therapy and follow-up were 81.8% and 78.9%, respectively, in the 160-mg group, and 86.4% and 84.2%, respectively, in the 320-mg group, showing no statistically significant difference between two treatment groups(p=0.68 and 0.68, respectively). S. pneumoniae(12 isolates) and H. influenzae(10 isolates) were the most prevalent pathogens. The MICs were lower for gemifloxacin than other quinolones against these key pathogens, and for S. pneumoniae, the MICs for gemifloxacin were considerably lower(${\leq}0.03$ ug/mL) than those for other quinolones, beta-lactams and macrolides. In the period on-therapy plus 30 days post-therapy, a total of 18 patients(26.9%) in the gemifloxacin 160mg group and 22 patients(31.4%) in the 320mg group reported at least one adverse event(AE). The most frequently reported AE was abdominal pain(3/67 patients, 4.5%) in the gemifloxacin 160mg group and increased level of hepatic enzyme(5/70 patients, 7.1%) in the 320mg group. The overall AE profiles for the two treatment groups were similar. Two out of 67 patients(3.0%) in the gemifloxacin 160mg group and 1/70 patients(1.4%) in the 320mg group reported at least one serious AE, however, none of which was considered by the investigator to be of suspected or probable relationship to study medication. Conclusion : The results of this study showed that gemifloxacin at doses of 160mg or 320mg once daily for 7 days in the treatment of acute exacerbations of chronic bronchitis(AECB) in adult Koreans was a very effective and safe treatment both clinically and bacteriologically.