• The Korean Society of Law and Medicine
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• v.21 no.1
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• pp.223-259
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• 2020

With COVID-19 spreading rapidly around the world, research and development issues on treatments and vaccines for the virus are of high interest. Among them, Remdesivir was the first to show noticeable therapeutic effects and began clinical trials, with each country authorizing the use of the drug through emergency approval. However, Gilead Co., Ltd., the developer of Remdesivir, received a lot of criticism from civic groups for submitting the application for the marketing authorization as an orphan drug. This is because when a new drug got a marketing authorization as an orphan drug could be granted an exclusive status for seven year. The long-term exclusive status of an orphan drug comes from the policy purpose of motivating pharmaceutical companies to develop treatment opportunities for patients suffering from rare diseases, which was not appropriate to apply to infectious disease treatments. This paper provides a review of the problems and improvement directions of the domestic system through comparative legal consideration against the United States, Europe and Japan for the statutes which give exclusive status to medicines. The domestic system has a fundamental problem that it does not have explicit provisions in the statute in the manner of granting exclusive status, and that it uses the review system to give it exclusive status indirectly. In addition, in the case of orphan drugs, the "Rare Diseases Management Act" and the "Regulations on Examination of Items Permission and Reporting of Drugs" provide overlapping review periods, and despite the relatively long monopoly period, there seems to be no check clause to recover exclusive status in the event of a change in circumstances. Given that biopharmaceuticals are difficult to obtain patents, the lack of such provisions is a pity of domestic legislation, although granting exclusive rights may be a great motivation to induce drug development. In the United States, given that the first biosimilar also has a one-year monopoly period, it can be interpreted that domestic legislation is quite strictly limited to granting exclusive status to biopharmaceuticals. The need for improvement of the domestic system will be recognized in that it could undermine local pharmaceutical companies' willingness to develop biopharmaceuticals in the future, and in that it is also necessary to harmonize international regulations. Taking advantage of the emergence of COVID-19 as an opportunity, we look again at the problems of the domestic system that grants exclusive rights to medicines and hope that an overall revision of the relevant legislation will be made to establish a unified legal basis.

• Pediatric Infection and Vaccine
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• v.27 no.1
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• pp.35-44
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• 2020

Purpose: This study aimed to investigate the clinical features of recurrent urinary tract infection (UTI) in children with vesicoureteral reflux (VUR) and to compare the causative uropathogen and antibiotic susceptibility between the first and recurrent UTI episodes. Methods: We retrospectively reviewed the medical records of children with VUR who had recurrent UTI. Group 1 included patients in whom the same pathogen caused the first and recurrent UTI episodes. Group 2 included patients in whom different pathogens caused the first and recurrent UTI episodes. Results: During a 13-year study period (2005-2018), 77 children with VUR experienced at least one episode of UTI. Among these, 47 patients (61.0%) had recurrent UTI. Of the children with recurrent UTI, 19 (40.4%) were in group 1 and 28 (59.6%) were in group 2. Escherichia coli was the most commonly isolated uropathogen (n=37; 39.4%) in both episodes of recurrent UTIs, followed by Klebsiella pneumoniae (n=18; 19.1%), Enterococcus faecalis (n=14; 14.9%), and Enterobacter aerogenes (n=7; 7.4%). Although the difference was not significant, the rate of resistance to the antibiotics ceftazidime, piperacillin/tazobactam, and trimethoprim-sulfamethoxazole increased in patients with the second episode of E. coli recurrence in group 1, and that to cefotaxime, ceftazidime, piperacillin/tazobactam, and meropenem increased in children with the second episode of E. aerogenes recurrence in group 1. Conclusions: When selecting empirical antibiotics for recurrent UTI in children with VUR, it is important to consider that the pathogen and antimicrobial susceptibility of the previous UTI are not always the same in recurrent UTIs.

• Pediatric Infection and Vaccine
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• v.8 no.1
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• pp.94-100
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• 2001

Purpose : Enterovirus is a common cause of aseptic meningitis and nonspecific febrile illness in young children. During the summer and fall months, enterovirus-infected young children are frequently admitted and evaluated to rule out bacterial sepsis and/or meningitis. The purpose of this study was to evaluate the relationship between nonpolio enterovirus infection and febrile illness in infants under 3 months of age during the summer, fall months by using a stool culture to identify the presence of enterovirus. Methods : Patients included febrile infants under 3 months of age admitted to Masan Fatima Hospital for sepsis evaluation from May 1999 to September 1999. Cultures were performed from stool and Cerebrospinal fluid samples and then were tested for enterovirus infection. Viral isolation and serotype identification were performed by cell culture and immunofluorescent testing. Enteroviruses not typed by immunofluorescent testing were confirmed by reverse transcription-polymerase chain reaction. Results : A total of 44 febrile infants were enrolled; of those, 20(45%) were positive for enterovirus. Two enterovirus culture-positive infants had concomitant urinary tract infection and one had Kawasaki disease. All infants infected with an enterovirus recovered without complications. Serotype of 20 enteroviruses were isolated from stool, 3 of echovirus type 9, 1 of echovirus type 11, 1 Coxsachievirus type B4, 15 of untyped enteroviruses. One untyped enterovirus was isolated in the CSF. Conclusion : Nonpolio enterovirus infections are associated with nonspecific febrile illnesses in infants under 3 months of age.

• Pediatric Infection and Vaccine
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• v.8 no.1
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• pp.101-106
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• 2001

Purpose : The outbreaks of measles in infants and school children have been reported recently, but there are no specific treatment of these patients except symptomatic therapy. This study was performed to evaluate the effectiveness of intravenous gammaglobulin(IVGG) therapy in acute febrile phase of measles. Methods : The 68 cases in measles were treated with single dose of IVGG(400~500 mg/kg), and 44 cases were treated with only symptomatic treatment during the periods of 14 months from Jan. 2000 to Feb. 2001. They were compared to duration of fever, rash, the levels of CRP and days of admission on both groups after treatment. Results : The results obtained follows. The average of age was $7.9{\pm}3.6$ year old, and male to female was 1.0 : 1.6. The duration of fever after admission was $2.4{\pm}1.2$ days in treated group and $5.7{\pm}2.4$ days in control group. The period of disappearance of systemic erythematous maculopapular rash was $4.5{\pm}1.3$ days in treated group, and $6.9{\pm}2.4$ days in control group. The durations of admission day were also shown significantly shorter duration of period in treated group(P<0.05). The levels of CRP were no significant difference between two groups before treatment. However, treated group was significantly shown by improved within 5 days after IVGG therapy(P<0.05). Conclusions : The single dose of IVGG(400~500 mg/kg) therapy is one of rapid and effective therapy for clinical symptoms and signs in acute high febrile phase of measles.

• Pediatric Infection and Vaccine
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• v.7 no.2
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• pp.233-239
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• 2000

Purpose : A great deal of youngsters suffer from otitis media, for which antimicrobials are frequently prescribed. Increased antimicrobial resistance forces physicians to judiciously use antimicrobial agents in treating patients with acute otitis media. There have however been few references with regard to otitis media in Korean children, and authors proceeded investigation to look for the causative agents of otitis media in Korean children and their antimicrobial susceptibility. Methods : The study included 65 patients younger than 15 years old who had been cared at the department of pediatrics and otolaryngology in Hanyang University Hospital from July 1994 to June 1999, and diagnosed of otitis media with otorrhea which contained microorganisms isolated in otorrhea culture. The medical records were reviewed for demographic data, isolated organisms and their antimicrobial susceptibility. Results : Among 65 patients, 37(57%) were boys and 28(43%) girls. Distribution of the patients was reciprocal to the age of the patients; 27 patients(41.5%) were younger than 1 year old, 24(36.9%) were 1 to 3 years old with the average of 2.9 years of age. Staphylococus aureus was isolated in 32 patients(49.2%), Streptococcus pneumoniae in 19 patients(29.2%) Haemophilus influenzae in 9 patients(13.8%), Streptococcus oralis in 3 patients(4.6%), Moraxella catarrhalis in 1 patient(1.5%). The isolated microorganisms were not different whether patients had cleft lip/palate or not. The antibiotic resistance rates of S. aureus were ${\geq}90%$ to erythromycin, imipenem, cephalothin, and clindamycin, 86.2% to oxacillin, 25% to chloramphenicol, 12.5% to trimethoprim/sulfamethoxazole(TMP/SMX), and 0% to vancomycin and teicoplanin. The antibiotic resistance rates of S. pneumoniae were 71.4% to penicillin and greater than 60% to erythromycin, tetracycline, TMP/SMX, 7.1% to chloramphenicol, and 0% to vancomycin and teicoplanin. The antibiotic resistance rates of H. influenzae were 55% to ampicillin and TMP/SMX, and 0% to chloramphenicol, ceftriaxone, aztreonam, imipenem and ciprofloxacin. Conclusion : With otorrhea culture, the causative organisms of otitis media appear to be S. aureus, S. pneumoniae and H. influenzae. The high antibiotic resistance rates of the isolated organisms should affect the choice of antibiotics in treating patients with otitis media. Prospective investigations utilizing tympanocentesis in microbiologic studies are needed.

• Pediatric Infection and Vaccine
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• v.5 no.1
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• pp.121-127
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• 1998

Purposes : This study was performed to evaluate the seropositivities and levels of term pregnant women and their neonates, and the transplacental transfer rate of maternal Epstein-Barr Virus-specific IgG(VCA IgG and EBNA IgG) from term pregnant women to their neonates. Subjects and Methods : During Jan. 1, 1997 to Mar. 31. 1997, we collected the 42 pairs of sera from pregnant women and umbilical cord of their neonates in Korea University Ansan Hospital. The serum levels of VCA IgG and EBNA IgG were measured by the ELISA method. Results : 1) The seropositivities of VCA IgG were 100% in mothers and neonates. There was no statistical difference of mean VCA IgG levels between mothers and neonates. There was significant correlation of VCA IgG levels between maternal sera and neonatal umbilical cord sera(correlation coefficient r=0.5214, P<0.001). 2) The seropositivities of EBNA IgG were 100% in mothers and neonates. There was no significant difference of the mean EBNA IgG levels between mothers and neonates. There was significant correlation of EBNA IgG levels between maternal sera and neonatal umbilical cord sera (correlation coefficient r=0.7244, P<0.001). 3) There was no correlation between VCA IgG and EBNA IgG levels of maternal sera. Conclusion : Seropositivities of EBV CA IgG and EBNA IgG of term-pregnant women and their neonates were 100% and no significant differences of antibody levels were found in two groups. It seems that EBV Antibody levels in Korean mothers and neonates were high enough to protect primary EBV infection during early infancy.

• Pediatric Infection and Vaccine
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• v.7 no.2
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• pp.225-232
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• 2000

Purpose : The use antimicrobial agents is one of the important strategies for the treatment and prophylaxis of microbial infections. But injudicious abuse and misuse of antimicrobial agents is problem to add an extra weight on medical fee, increase of resistant bacteria and side effects according to the antibiotic use. This study was performed to establish the pertinent use of antimicrobial agent in Chonbuk National University Hospital(CNUH). Characteristics of antibiotics use was analysis by reviewing the medical records of patients admitted to CNUH during the period of May 1998. Methods : One thousand eight hundred and thirty three patients were enrolled in this study(medical division 1,014 cases, surgical division 819 cases). Medical records were retrospectively reviewed to classify the rate of antibiotics use, name of antibiotics used, appropriateness of antibiotics use. Results : The overall rate of antibiotic usage in CNUH was 67.2%(1,231/1,833), showing higher rate in surgical division(89.6%) compare to that of medical division(49.0%). Among 1,231 patients to whom antimicrobial agents were given, only 125(10.2%) were treated with single antimicrobial agents. 311(25.3%) were treated with two antimicrobial agents, and 795(64.5%) patients received 3 or more antibiotics. ${\beta}$-lactams(56.4%) were most frequently used followed by aminoglycosides(35.3%), the others(4.9%) and quinolons(3.4%). Amoxicillin-clavulanate was the mostly commonly used antibiotics followed by amoxicillin and unasyn. Prophylactic use of antibiotics was carried in seven hundred six patients(57.4%), mostly in surgical division, which can be considered somewhat inappropriate in the initiation time and duration of antibiotic use. Conclusion : Importance of monotherapy and appropriate prophylactic antibiotic use should be emphasized. Strategies of antibiotics use, such as restriction of drug use, continuous monitoring system, flow sheet system should be considered to reduce antibiotics use and establish the appropriate use of antibiotics as well as inhibiting the occurrence of resistant strains.

• Pediatric Infection and Vaccine
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• v.7 no.2
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• pp.218-224
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• 2000

Purpose : In Korea, vivax malaria has been reemerged since 1993 after being abscent for more than 10 years. There are several possibilities of casuality of recent epidemic, although it is still unclear. The epidemiologic studies including case analysis and entomological reseach have been undertaken for a successful control measure. But, unfortunately those studies have been rarely dealt with cases of children. Therefore, this study was designed to figure out the characteristics of epidemiolgic and clinical features in children with indigenous vivax malaria. Methods : The study 21 cases below 15 years of age, who were diagnosed as vivax malaria and resided in kyounggi-do province area during 1998. 9~1999. 8. We retrospectively analyzed epidemiologic data concernig with occurrence of vivax, and clinical manifestations, abnormal laboratory findings and outcomes including therapeutic responses. Results : All cases were inhabitants of the endemic areas for vivax malaria in northwestern part of Kyonggi-do or western Kangwon-do, and Paju-gun was the most prevalent. Indigenous malaria cases of this study were more prevalent in children above 10 years old age, and in male. Seasonally, vivax malaria in children occurred throughout the year except January, March and November, and the incidence was the highest in July. Clinical manifestations revealed that 48 hour cyclic fever pattern was the major fever pattern, and other symptoms such as headache, vomiting, poor appetites, chilling, abdominal pain and diarrhea were concomitantly developed. And splenomegaly revealed the main abnormal findings on physical examination, and anemia was the most frequent abnormal finding in laboratory examinations. Young trophozoite was frequently observed on peripheral blood smears. The therapeutic responses of chlorquine were very good in all cases, and no recurrence developed in follow up cases. Conclusion : Geographical and seasonal occurrence distributions of indigenous vivax malaria cases in children were very similar to those of adults as followings; Inhabitants of the endemic region, more prevalent in male, and more common during the summer season. Clinically, 48 hour cyclic fever pattern, splenomegaly and anemia were most frequent and important manifestations in children cases, and clinical courses were not serious. On blood smears, young trophozoite was most dominantly examined in children. Generally, the therapeutic outcomes were excellent, and recurrences were not observed.

• Pediatric Infection and Vaccine
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• v.5 no.1
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• pp.104-114
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• 1998

Purpose : Enteroviruses are the most common cause of aseptic meningitis. The epidemics of aseptic meningitis in 1993 and 1996 were mostly caused by echovirus type 9. Identification of the causative virus of aseptic meningitis in epidemics, is very important not only for diagnosis but also for epidemiologic purpose. The purpose of this study was to identify the causative virus and investigate the relationship between aseptic meningitis, prevailed in Masan and surrounding areas in Kyoungsangnamdo in 1997, and its clinical manifestations. Methods : One hundred twenty eight cerebrospinal fluid(CSF) and 239 stool specimens were obtained from 239 patients(213 children and 26 adult patients) with aseptic meningitis were admitted to Masan Fatima Hospitals from March to October 1997. Viral isolation and serotype identification was performed by cell culture and immunofluorescent test. Enteroviruses not typed by immunofluorescent test was confirmed by reverse transcription-polymerase chain reaction(RT-PCR). Results : 1) The peak incidence was noted in June. 2) The age of 239 patients(pediatrics-213 cases, internal medicine-26 cases) that were diagnosed ranged from neonate to 35 years, the age of the patients of pediatrics ranged from neonate to 15years(mean 4.9 years), the age of the patients of internal medicine (above 16 years) ranged from 16 years to 35 years(mean 24.2 years). 3) Fifty-three(41.4%) of 128 CSF specimens were positive for enteroviruses, and 163(68.2%) of 239 stool specimens were positive for enteroviruses respectively. 4) Serotypes of 53 enteroviruses isolated from CSF were 16(30.2%) of echovirus type 30, 6(11.3%) of echovirus type 6, 1 of echovirus type 4, 4 of untyped echovirus, 1 of coxsackievirus type B5, and 24 isolates of untyped enteroviruses. Of 163 enterovirus isolated from stool were 72(44.2%) of echovirus type 30, 21(12.9%) of echovirus type 6, 1 of echovirus type 4, 17(10.4%) of undetermined subtyped echovirus, 1 of coxsackievirus type B5, 2 of A24, 3 of undetermined subtyped coxsackievirus type B, and 46 isolates of untyped enterovirus. Conclusion : There were epidemics of aseptic meningitis in the central areas of Kyoungsangnamdo from March to October 1997. The main causative organism was thought to be the echovirus type 30, and echovirus type 4, 6, coxsackievirus B5 and A24 were also thought to contribute to the epidemics.

• Pediatric Infection and Vaccine
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• v.7 no.2
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• pp.211-217
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• 2000

Purpose : Salmonellosis including typhoid fever is still prevalent in Korea. Recently it has been reported that the incidence of salmonella gastroenteritis is increasing with a reduction of typhoid fever. We studied the clinical and laboratory features of salmonellosis. Methods : We evaluated the clinical records of 83 patients with salmonellosis who had been confirmed by stool culture from 1994 to 1999. Results : Annual incidence of salmonellosis showed an increasing tendency during recent 4 years. Seasonally, summer(45.8%) was the most prevalent, followed by fall(32.5%). Male to female ratio was 1.4 : 1. In age distribution, 64 cases(77.1%) were under 5 year-old, and 18 cases(21.7%) were younger than 1 year-old. Clinical features included diarrhea(96.4%), fever(91.6%), vomiting(49.4%), bloody stool(42.1%), abdominal pain(40.1%) and tenesmus(12.0%). In serogroups, there was no group A and group B, group C, group D(including 2 cases of S.typhi) and group E were in 41.0%(34 cases), 3.6%(3 csaes), 51.8%(43cases) and 3.6%(3 cases), respectively. In Widal test, 5 cases(13.5%) and 1 case(2.7%) of group B, C and E(total 37 cases) were observed the O titer above 1 : 80 and 1 : 320, respectively. However, in 36 cases of group D, 19 cases(52.7%) and 9 cases(25.0%) were above the O titer 1 : 80 and 1 : 320, respectively. Antibiotics resistant rates to ampicillin, trimethoprim/sulfamethoxazole and chloramphenicol were 23.2%, 10.1% and 51.4%, respectively. Conclusion : Salmonellosis has become a common cause of gastroenteritis in children, especially under the pre-school age. Isolation of salmonella is neccessary for accurate diagnosis of gastroenteritis and typhoid fever. A careful attention of the use of antibiotics is needed to reduce the muilti-drug resistant strains.