Yeon Sook Kim

Clinical Outcomes of Pneumococcal Pneumonia Caused by Antibiotic-Resistant Strains in Asian Countries: A Study by the Asian Network for Surveillance of Resistant Pathogens

To evaluate the clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries, we performed a prospective observational study of 233 cases of adult pneumococcal pneumonia in 9 Asian countries from January 2000 to June 2001. Among 233 isolates, 128 (55%) were not susceptible to penicillin (25.3% were intermediately susceptible, and 29.6% were resistant). Clinical severity of pneumococcal pneumonia was not significantly different between antibiotic-resistant and antibiotic-susceptible groups. Mortality rates among patients with pneumococcal pneumonia caused by penicillin-, cephalosporin-, or macrolide-resistant strains were not higher than those with antibiotic-susceptible pneumococcal pneumonia. Bacteremia and mechanical ventilation were significant risk factors for death, but any kind of antibiotic resistance was not associated with increased mortality due to pneumococcal pneumonia. Outcome of pneumococcal pneumonia was not significantly affected by drug resistance, and current antimicrobial regimens are mostly effective in the treatment of pneumococcal pneumonia, despite the widespread emergence of in vitro resistance.

Prenatal development of the human mandible

In an effort to better understand the interrelationship of the growth and development pattern of the mandible and condyle, a sequential growth pattern of human mandibles in 38 embryos and 111 fetuses were examined by serial histological sections and soft X‐ray views. The basic growth pattern of the mandibular body and condyle appeared in week 7 of fertilization. Histologically, the embryonal mandible originated from primary intramembranous ossification in the fibrous mesenchymal tissue around the Meckel cartilage. From this initial ossification, the ramifying trabecular bones developed forward, backward and upward, to form the symphysis, mandibular body, and coronoid process, respectively. We named this initial ossification site of embryonal mandible as the mandibular primary growth center (MdPGC). During week 8 of fertilization, the trabecular bone of the mandibular body grew rapidly to form muscular attachments to the masseter, temporalis, and pterygoid muscles. The mandible was then rapidly separated from the Meckel cartilage and formed a condyle blastema at the posterior end of linear mandibular trabeculae. The condyle blastema, attached to the upper part of pterygoid muscle, grew backward and upward and concurrent endochondral ossification resulted in the formation of the condyle. From week 14 of fertilization, the growth of conical structure of condyle became apparent on histological and radiological examinations. The mandibular body showed a conspicuous radiating trabecular growth pattern centered at the MdPGC, located around the apical area of deciduous first molar. The condyle growth showed characteristic conical structure and abundant hematopoietic tissue in the marrow. The growth of the proximal end of condyle was also approximated to the MdPGC on radiograms. Taken together, we hypothesized that the MdPGC has an important morphogenetic affect for the development of the human mandible, providing a growth center for the trabecular bone of mandibular body and also indicating the initial growth of endochondral ossification of the condyle. Anat Rec 263:314–325, 2001.

Fecal carriage of serotype K1 Klebsiella pneumoniae ST23 strains closely related to liver abscess isolates in Koreans living in Korea

We determined the fecal carriage rate of serotype K1 Klebsiella pneumoniae in healthy Koreans and studied their genetic relationship with liver abscess isolates. We compared the carriage according to the country of residence. The stool specimens were collected through health promotion programs in Korea. K. pneumoniae strains were selected and tested for K1 by PCR. Serotype K1 isolates were characterized by multilocus sequence typing and pulsed field gel electrophoresis. A total of 248u2009K. pneumoniae isolates were obtained from 1,174 Koreans. Serotype K1 was identified in 57 (4.9%), of which 54 (94.7%) were ST 23 and were closely related to the liver abscess isolates. Participants aged >25xa0years showed a higher fecal carriage rate than those ≤ 25 (Pu2009=u20090.007). The proportion of serotype K1 out of K. pneumoniae isolates in foreigners of Korean ethnicity who had lived in other countries was lower compared with those who had lived in Korea (5.6% vs 24.1%, Pu2009=u20090.024). A substantial proportion of Koreans >25xa0years carries serotype K1u2009K. pneumoniae ST23 strains, which are closely related to liver abscess isolates. Differences in carriage rates by country of residence suggests that environmental factors might play an important role in the carriage of this strain.

High Rate of Resistance to Quinupristin-Dalfopristin in Enterococcus faecium Clinical Isolates from Korea

ABSTRACT We tested the in vitro susceptibilities of 603 enterococcal isolates from eight tertiary-care hospitals in Korea. The quinupristin-dalfopristin resistance rate in Enterococcus faecium was very high (25 isolates, 10.0%). It was suggested that both clonal spread and the sporadic emergence of quinupristin-dalfopristin-resistant isolates may explain the high prevalence of quinupristin-dalfopristin resistance in Korea.

Spread of Mutant Middle East Respiratory Syndrome Coronavirus with Reduced Affinity to Human CD26 during the South Korean Outbreak

ABSTRACT The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26. IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure. Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.

Multicenter Prospective Observational Study of the Comparative Efficacy and Safety of Vancomycin versus Teicoplanin in Patients with Health Care-Associated Methicillin-Resistant Staphylococcus aureus Bacteremia

ABSTRACT The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (n = 134) or teicoplanin (TEC) (n = 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 μg/ml (MIC50 and MIC90, 1.5 μg/ml), and the TEC MIC ranged from 0.5 to 8 μg/ml (MIC50, 3 μg/ml; MIC90, 6 μg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.

Bio-distribution and anti-tumor efficacy of PEG/PLA nano particles loaded doxorubicin

As a more effective in vivo drug delivery system, several methods loading anti-cancer drugs to biodegeradable and biocompatible nano-particles have been explored and developed. Supposedly due to the enhanced permeability and retention (EPR) effect, systemic administration of these nano-particles have been found to result in accumulation of nano-particles into solid tumors. In this study, we prepared nano-particles using polyethylene glycol (PEG)/poly-l-lactide (PLLA) diblock copolymer and loaded doxorubicin into these nano-particles (Nano-dox). The fabricated nano-particles exhibited sustained release kinetics of the drug in vitro. To follow the in vivo biodistribution of 200–350 nm sized nano-dox particles in tumor (syngenic renal cell adenocarcinoma: RENCA) bearing mouse, the carboxylfluorescenin diacetate succinimidyl ester (CFSE) was loaded into the nano-particles. Nano-dox accumulated preferentially in tumors; however, in terms of its anti-tumor efficacy, it did not show any marked benefits, compared to freely-administered doxorubicin. This result suggests the need to re-consider and evalute what type of anti-cancer reagents we to be used in the ongoing efforts of coupling drug delivery system with tumor EPR effects.

Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea

Background A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. Materials and Methods Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. Results In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. Conclusion Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.

Evaluation of Ceftriaxone Utilization at Multicenter Study

Background/Aims As bacterial resistance to antimicrobial agents has grown due to the increasing use of antimicrobial agents, we sought to evaluate the suitability of ceftriaxone usage (representative of third generation cephalosporins) at 10 university hospitals in Korea. Methods We prospectively evaluated the appropriateness of antibiotic usage in 400 adult patients who received ceftriaxone between February 1, 2006 and June 30, 2006. Drug utilization evaluation (DUE) methods were based on standards set forth by the American Society of Hospital Pharmacists. The DUE criteria used in this study were modified to be more suitable in our hospital setting: justification of drug use, critical and process indications, complications, and outcome measures. Results The average patient age was 64.4 years. The utilization of ceftriaxone was appropriate in 262 cases (65.5%) for the justification of use, while inappropriate use was observed in 138 cases (34.5%). Common reasons for inappropriate use of ceftriaxone included continued empiric use for presumed infections, prophylactic perioperative injection, and empiric therapy for fever. Most of the critical indications showed a high rate of suitability (66.5-98.5%). Complications occurred in 37 cases (9.3%). With respect to outcome measures, clinical responses were observed in 60.7% of cases, while only 15.7% of cases showed evidence of infection eradication via negative cultures. Conclusions Appropriate use (65.5%) of ceftriaxone was higher than inappropriate use (34.5%) at university hospitals in Korea. Inappropriate utilization, however, including continued empiric use for presumed infections and prophylactic perioperative injection remained high. Intensification of educational programs and antibiotic control systems for ceftriaxone is needed to improve the suitability of antimicrobial use.

Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cutaneous and exposed tongue wounds

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.