• YAKHAK HOEJI
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• v.51 no.2
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• pp.108-114
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• 2007

The predominant Macrolides-Lincosamide-Streptogramin B (MLS$_B$) antibiotics resistance genes in staphylococci are erm(A) and erm(C). There is the phenomenon that the ratio of constitutively MLS$_B$ antibiotics resistance (cMLS) in erm(A) is much higher than in erm(C). Thus, we confirmed that the difference of the mutation ratio between erm(A) and erm(C) makes the phenomenon. We examined 8 staphylococci carrying inducibly expressed (iMLS) erm(A) or erm(C) genes. After overnight incubation in the presence of the non-inducer MLS$_B$ antibiotics, spontaneous mutants constitutively expressed MLS$_B$ resistance were selected. Against our expectation, the mutation ratio of erm(A) was lower than erm(C). Therefore, possibilities of other factors determining the ratio of cMLS phenotype might be concerned. All the mutants showed sequence alterations in translational attenuator and all the alterations seemed to give rise to change the second structure of mRNA to express constitutively. For erm(A), 4 different types of sequence deletions ranging from 72 bp to 122 bp and 3 different types of duplications ranging 24 bp to 93 bp were detected. Also, there were 9 different types of duplications ranging 15bp to 154bp in erm(C).

• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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• pp.1-14
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• 1999

Vancomycin-resistant Enterococci (VRE) have recently emerged in Korean hospitals, as well as in those of other countries. VRE have been partially attributed to the overuse and misuse of vancomycin. The mecbanisms of VRE resistance are related to VanA, VanB, and VanC. Both VanA and VanB produce abnormal ligase enzymes to form D-ala-D-lactate termini in E. faecium and E. faecalis, instead of D-ala-D-ala termini. Meanwhile, Van C produces D-ser-D-ala termini in E. gallinarum and E. casseliflavus. These abnormal termini have a low affinity to vancomycin. As a result, VRE avoid the activity of vancomycin by these mechanisms. Unfortunately, there is no approved therapy for the treatment of VRE. Thus, available but uncommonly prescribed antibiotics (due to their toxicity or unproven efficacy) may become possible options. They include chloramphenicol, novobiocin, fosfomycin, and bacitracin. The combination therapy of available agents may also be the other options. They include high doses of a penicillin- or ampicillin-aminoglycoside combination, high doses of an ampicillin/sulbactam and aminoglyoosidcs combination, an ampicillin and vancomycin combination, and a ciprofloxacin, aminoglycosides, and rifampin combination. With respect to the near future, many types of investigational agents will most likely expand their treatment options for VRE. Teicoplanin, a glycopeptide, can be used for VanB- and VanC-related VRE. LY333328, a new generation of glycopeptide, is effective in treating VanA as well as VanB and VanC. RP59500 (quinupristin/dalfopristin), a streptogramin, is effective in treating vancomycin-resistant E. faecium. New generation quinolones (especially clinatloxacin) are potential options for the treatment of VRE, even though they cannot work as effectively against VRE as they can against Staphylococci. Both glycylcyclines (a new generation of tetracyclines) and ketolides (a new generation of macrolides) show good activity against Enterococci, regardless of vancomycin susceptibility. Oxazolidinones (i. e. eperezolid and 1inezolid) and everninomicins (i. e. SCH27899) are new groups of antibiotics, which also demonstrate good activity against VRE. It is imperative that clinical pharmacists take the responsibility of investigating new treatment options for VRE in order to combat this growing problem throughout the world.

• Journal of Korean Medical Science
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• v.33 no.43
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• pp.268.1-268.11
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• 2018

Background: We aimed to compare the therapeutic efficacy of prolonged macrolide (PMC), corticosteroids (CST), doxycycline (DXC), and levofloxacin (LFX) against macrolide-unresponsive Mycoplasma pneumoniae (MP) pneumonia in children and to evaluate the safety of the secondary treatment agents. Methods: We retrospectively analyzed the data of patients with MP pneumonia hospitalized between January 2015 and April 2017. Macrolide-unresponsiveness was clinically defined with a persistent fever of ${\geq}38.0^{\circ}C$ at ${\geq}72$ hours after macrolide treatment. The cases were divided into four groups: PMC, CST, DXC, and LFX. We compared the time to defervescence (TTD) after secondary treatment and the TTD after initial macrolide treatment in each group with adjustment using propensity score-matching analysis. Results: Among 1,165 cases of MP pneumonia, 190 (16.3%) were unresponsive to macrolides. The proportion of patients who achieved defervescence within 48 hours in CST, DXC, and LFX groups were 96.9% (31/33), 85.7% (12/14), and 83.3% (5/6), respectively. The TTD after initial macrolide treatment did not differ between PMC and CST groups (5.1 vs. 4.2 days, P = 0.085), PMC and DXC groups (4.9 vs. 5.7 days, P = 0.453), and PMC and LFX groups (4.4 vs. 5.0 days, P = 0.283). No side effects were observed in the CST, DXC, and LFX groups. Conclusion: The change to secondary treatment did not show better efficacy compared to PMC in children with macrolide-unresponsive MP pneumonia. Further studies are needed to guide appropriate treatment in children with MP pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.82 no.1
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• pp.15-26
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• 2019

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

• Journal of Veterinary Science
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• v.21 no.4
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• pp.57.1-57.11
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• 2020

Background: Streptococcus dysgalactiae subspecies equisimilis (SDSE) acts as an etiological agent for lameness, neurological signs, and high mortality in pigs. Despite its importance in pig industries and zoonotic potential, little is known about the effects of this pathogen. Objectives: This study aimed to determine the molecular characteristics and antimicrobial resistance of SDSE strains isolated from diseased pigs. Methods: A total 11 SDSE isolates were obtained from diseased pigs. Bacterial identification, PCR for virulence genes, emm typing, and antimicrobial resistance genes, multilocus sequence typing, and antimicrobial susceptibility test were performed. Results: Nine isolates were from piglets, and 8 showed lameness, sudden death, or neurological signs. The isolates were PCR-positive for sla (100%), sagA (100%), and scpA (45.5%), and only 1 isolate amplified the emm gene (stL2764). Eight different sequence types were detected, categorized into 2 clonal complexes and 4 singletons. All the isolates in this study were included in a small cluster, which also contained other strains derived from humans and horses. The minimum inhibitory concentrations for the tested beta-lactams were low, while those for macrolides, tetracyclines, and fluoroquinolones were relatively high. PCR analysis of the macrolide and tetracycline resistance genes demonstrated that the isolates carried erm(B) (18.2%, n = 2), mef(A/E) (9.1%, n = 1), tet(M) (18.2%, n = 2), and tet(O) (90.2%, n = 10). Two isolates presented a mutation in parC, which is associated with fluoroquinolone resistance. Conclusion: This study provided insight into swine-derived SDSE, as it is related to veterinary medicine, and elucidated its zoonotic potential, in the context of molecular epidemiology and antimicrobial resistance in public health.

• Journal of Microbiology and Biotechnology
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• v.32 no.7
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• pp.911-917
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• 2022

As valuable antibiotics, microbial natural products have been in use for decades in various fields. Among them are polyene compounds including nystatin, amphotericin, and nystatin-like Pseudonocardia polyenes (NPPs). Polyene macrolides are known to possess various biological effects, such as antifungal and antiviral activities. NPP A1, which is produced by Pseudonocardia autotrophica, contains a unique disaccharide moiety in the tetraene macrolide backbone. NPP B1, with a heptane structure and improved antifungal activity, was then developed via genetic manipulation of the NPP A1 biosynthetic gene cluster (BGC). Here, we generated a Streptomyces artificial chromosomal DNA library to isolate a large-sized NPP B1 BGC. The NPP B1 BGC was successfully isolated from P. autotrophica chromosome through the construction and screening of a bacterial artificial chromosome (BAC) library, even though the isolated 140-kb BAC clone (named pNPPB1s) lacked approximately 8 kb of the right-end portion of the NPP B1 BGC. The additional introduction of the pNPPB1s as well as co-expression of the 32-kb portion including the missing 8 kb led to a 7.3-fold increase in the production level of NPP B1 in P. autotrophica. The qRT-PCR confirmed that the transcription level of NPP B1 BGC was significantly increased in the P. autotrophica strain containing two copies of the NPP B1 BGCs. Interestingly, the NPP B1 exhibited a previously unidentified SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibition activity in vitro. These results suggest that the Streptomyces BAC cloning of a large-sized, natural product BGC is a valuable approach for titer improvement and biological activity screening of natural products in actinomycetes.

• Journal of Korean Society of Environmental Engineers
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• v.32 no.3
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• pp.278-286
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• 2010

Veterinary antibiotics have been used to treat disease and to promote growth of livestock. However, the total amount of veterinary antibiotics in Korea was much greater than other developed countries, and there is a high potential to release residual of antibiotics to environment. Consequentially, released antibiotics into the environment produces antibiotic resistant bacteria and causes adverse effects on human health. The objective of this research was to monitor antibiotic concentration in the environment adjacent to facilities which compose chicken manure. Total of 10 antibiotics were selected based on the total amount of higher usage in Korea, and its residuals were measured from surface water, soil and sediment. The frequencies of detected antibiotics were ranged 31-92% from soil, 0-93% from water, and 33-93% from sediment. Generally, a higher frequency was observed in soil or sediment than water. Different ranges in concentration among 4 different antibiotic groups was found from not detected(N.D.) to 35.6 ${\mu}g/kg$ for soil, N.D. to 19.2 ${\mu}g/L$ for water and N.D. to 114.3 ${\mu}g/kg$ for sediment. Our findings suggest that solid phase such as soil and sediment is a critical component to be needed to conduct the environmental impact assessment of antibiotics.

• Clinical and Experimental Pediatrics
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• v.58 no.6
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• pp.211-217
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• 2015

Purpose: Mycoplasma pneumoniae (MP) infection is a major cause of respiratory infection in school-aged children. Extrapulmonary manifestations of MP infection are common, but liver involvement has been rarely reported. The aim of this study was to determine the clinical characteristics of MP-associated hepatitis. Methods: This prospective study included 1,044 pediatric patients with MP infection diagnosed serologically with MP IgM at one medical center from January 2006 to December 2012. Eighty of these patients had elevated levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), each greater than 50 IU/L, without any other specific liver disorder and were compared with the 964 children without liver disorders. Results: In total, 7.7% of patients with MP infection had a diagnosis of hepatitis, especially in fall and winter. The ratio of male to female patients was 1.7:1, and the mean age of the patients was 5 years and 5 months. The most common symptoms were cough, fever, and sputum. Anorexia was the most common gastrointestinal symptom, followed by nausea/vomiting, diarrhea, and abdominal pain. Mean levels of AST and ALT were 100.65 IU/L and 118.73 IU/L, respectively. Serum AST/ALT level was normalized within 7.5 days on average without complications. The mean duration of hospitalization (11.3 days) was longer for children with hepatitis than for those without hepatitis (P=0.034). Conclusion: MP-associated hepatitis is not uncommon and has a relatively good prognosis. Therefore, clinicians should be concerned about liver involvement in MP infection but avoid further unnecessary evaluation of hepatitis associated with MP.

• Korean Journal of Environmental Agriculture
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• v.29 no.3
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• pp.273-281
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• 2010

Concentration of antibiotics including a tetracycline group (TCs) of tetracycline (TC), chlortetracycline (CTC), and oxytetracycline (OTC), a sulfonamide group (SAs) of sulfamethoxazole (SMX), sulfathiazole (STZ), and sulfamethazine (SMT), an ionophore group (IPs) of lasalocid (LSL), monensin (MNS), and salinomycin (SLM), and a macrolide group (MLs) of tylosin (TYL) was determined from samples collected from the agricultural soil, stream water, and sediment. For the agricultural soil samples, the concentration of TCs had the highest value among all tested antibiotic's groups due to its high accumulation rate on the surface soils. The lower concentrations of SAs in the agricultural soils may be resulted from its lower usage and lower distribution coefficient (Kd) compared to TCs. The concentration of TCs in stream water was significantly increased through June to September. It would be likely due to soil loss during an intensive rainfall event and a reduction of water level after the monsoon season. A significant amount of TCs in the sediment was also detected due to its accumulation from runoff, which occurred by complexation of divalent cations, ion exchange, and hydrogen bonding among humic acid molecules. To ensure environmental or human safety, continuous monitoring of antibiotics residues in surrounding ecosystems and systematic approach to the occurrence mechanism of antibiotic resistant bacteria are required.

• Tuberculosis and Respiratory Diseases
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• v.65 no.5
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• pp.410-415
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• 2008

Bronchiolitis obliterans (BO) is a serious noninfectious complication following an allogeneic bone marrow transplant (BMT). A 21-year-old female received an allogeneic BMT as a treatment for myelodyplastic syndrome. Four months after the BMT, progressive dyspnea developed and BO was also diagnosed by a lung biopsy. The patient was administered steroid and immunosuppressive agents for 1 year but there was no improvement in pulmonary function. Azithromycin was prescribed (500 mg q.d. for 3 days followed by 250 mg three time a week) because macrolides might decrease the inflammatory reaction leading to BO. The patient's pulmonary function improved after administration of azithromycin for 1 year. The forced expiratory volume in a one second ($FEV_1$) increase was 220 mL (28.2%) and the forced vital capacity (FVC) increase was 460 mL (25.7%). We report the improvement in the pulmonary function after the administration of azithromycin for 1 year in a patient with BO after a BMT.