• Bulletin of the Korean Chemical Society
• /
• v.18 no.5
• /
• pp.475-478
• /
• 1997

(3R,4R)-4-Acetoxy-3-[(1'R-tert-butyldimethylsilyloxy)ethyl]-2-azetidinone, one of the best synthons for carbapenems and penems was efficiently synthesized from readily available L-threonine via double azetidinone ring formation.

• Childhood Kidney Diseases
• /
• v.21 no.2
• /
• pp.128-135
• /
• 2017

Purpose: Extended-spectrum ${\beta}$-lactamase-producing bacteria-induced urinary tract infections are increasing and require more potent antibiotics such as carbapenems. We evaluated the clinical significance of extended-spectrum ${\beta}$-lactamase -urinary tract infection in children younger than 5 years to select proper antibiotics and determine prognostic factors. Differences were compared between age groups. Methods: We retrospectively studied 288 patients with their first febrile urinary tract infection when they were younger than 5 years. Patients were divided into extended-spectrum ${\beta}$-lactamase-positive and extended-spectrum ${\beta}$-lactamasenegative urinary tract infection groups. Clinical characteristics and outcomes were compared between the groups; an infant group was separately analyzed (onset age younger than 3 months). Results: Extended-spectrum ${\beta}$-lactamase urinary tract infection occurred in 11 % patients who had more frequent previous hospitalization (P=0.02) and higher recurrence rate (P=0.045). During the antimicrobial susceptibility test, the extended-spectrum ${\beta}$-lactamase-positive urinary tract infection group showed resistance to third-generation cephalosporins; however, 98% patients responded clinically. In the infant group, extended-spectrum ${\beta}$-lactamase-positive urinary tract infection occurred in 13% patients and was associated with a longer pre-onset hospitalization history (P=0.002), higher C-reactive protein level (P=0.04), and higher recurrence rate (P=0.02) than that in the older group. Conclusion: Extended-spectrum ${\beta}$-lactamase urinary tract infection requires more attention because of its higher recurrence rate. The antimicrobial susceptibility test demonstrated resistance to third-generation cephalosporins, but they can be used as first-line empirical antibiotics because of their high clinical response rate. Aminoglycosides can be second-line antibiotics before starting carbapenems when third-generation cephalosporins do not show bactericidal effects for extended-spectrum ${\beta}$-lactamase urinary tract infection.

• Childhood Kidney Diseases
• /
• v.25 no.1
• /
• pp.22-28
• /
• 2021

Purpose: The purpose of this study was to investigate the clinical outcomes of non-carbapenem treatment for urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) in young children. Methods: We retrospectively reviewed the medical records of children under 2 years of age who were diagnosed and treated for UTIs caused by ESBL-producing E. coli from September 2014 to March 2020. Results: Forty-three children under 2 years of age were treated with non-carbapenem antimicrobials for UTIs caused by ESBL-producing E. coli without bloodstream infections. The overall clinical and microbiological success rates for empirical antimicrobial treatment were 90.7% and 97.7%. Three of the patients (7.0%) experienced a relapse of UTI within a month. An in vitro susceptibility test showed that two patients were sensitive and one was resistant to the antimicrobial treatments. Furthermore, there were no significant differences in the time to defervescence, clinical success, microbiological success, and relapse rate between the susceptible (n=13) and non-susceptible groups (n=30). Conclusion: In this study, the overall relapse rate of patients treated with non-carbapenem antimicrobials was 7.0%. The patients showed high success rates in the clinical and microbiological responses to the non-carbapenems regardless of the results of the in vitro antimicrobial susceptibility test. These results provide evidence that non-carbapenems may be viable alternative treatments for UTIs caused by ESBL-producing E. coli.

• YAKHAK HOEJI
• /
• v.40 no.2
• /
• pp.212-217
• /
• 1996

Streptomyces cattleya is a producer of carbapenem antibiotics, thienamycin and N-acetylthienamycin, which have potent and broad-spectrum antibacterial activities. We stud ied on strain improvement for antibiotic productivity of S. cattleya by transformation technique which employed S.cattleya protoplasts and chromosomal DNAs of glutamic acid producers: Corynebacterium glutamicum and Arthrobacter simplex. 150 Transformant strains were cultured and bioassayed using Bacillus subtilis and Staphylococcus aureus as test organisms. 8.7% of transformants tested showed 1.4~2.6 fold higher productivities than wild type which produced $1.61{\pm}0.67{\mu}g/ml$. The best transformant produced $8.36{\pm}2.84{\mu}g/ml$ carbapenems.

• Pediatric Infection and Vaccine
• /
• v.16 no.1
• /
• pp.6-12
• /
• 2009

There are relatively few novel antimicrobial agents despite the dramatic increase in antimicrobial resistance and multiple drug resistance of clinical isolates worldwide. Vancomycin is still the most widely used antibiotic for treating resistant Gram-positive coccal infections in children, especially for methicillin-resistant Staphylococcus aureus. For children with Gram-positive coccal infections where vancomycin is not effective or older therapeutic agents cannot be tolerated, linezolid, quinupristin-dalfopristin or daptomycin may be useful in the appropriate clinical setting. For Gram-negative bacterial infections, new carbapenems await clinical application. Tebipenem pivoxil is a novel oral carbapenem undergoing clinical trials for acute otitis media in pediatric patients. Antiviral drug development is now progressing at the pace of antibiotic development 30 years ago. Newer antiviral agents used for the treatment of herpes viruses and hepatitis C virus infections in children are included in this review.

• Bulletin of the Korean Chemical Society
• /
• v.8 no.1
• /
• pp.15-19
• /
• 1987

Preparation of optically pure (3R, 4R)-4-acetoxy-3-[(1R)-1-hydroxyethyl]azetidin-2-o ne derivatives, which can be employed as starting materials for synthesis of carbapenem and penem antibiotics, was established in high efficiency from 6-amino-penicillanic acid (6-APA). 6-APA was diazotized and brominated to give 6, 6-dibromopenicillanic acid and its methyl ester was metalated with methylmagnesium bromide and condensed with acetaldehyde. The product, methyl 6-bromo-6-(1-hydroxyethyl)penicillanate was reduced with Zn-$NH_4Cl-NH_4OH$-acetone efficiently to give methyl 6-(l-hydroxyethyl)-penicillanate, which was protected either with ${\beta},{\beta},{\beta}$ -trichloroethoxycarbonyl group or with t-butyldimethylsilyl group. The thiazolidine rings of these compounds were cleaved by treatment of mercury(II) acetate in acetic acid and permangante in acetone in sequence to afford the desired optically pure final products.

• Genomics & Informatics
• /
• v.20 no.4
• /
• pp.47.1-47.13
• /
• 2022

Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection in nosocomial settings. As reported by the World Health Organization, carbapenem-resistant Enterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgent threat, and the greatest concern is that these bacterial pathogens may acquire genetic traits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expand antibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells; however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation protein domain, suggesting a new potential site as a drug target. DNA methylation regulates the attenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could be a novel antibiotic.

• Journal of the Korean Chemical Society
• /
• v.33 no.5
• /
• pp.545-550
• /
• 1989

When (3R,4R)-1-(1-benzyloxycarbonyl-2-methyl-1-propenyl)-4-mercapto-3-phenylacetamidoazetidin-2-one(8) was reacted with carbon disulfide and alkyl halides in the presence of triethylamine, the ${\beta}$-lactam ring was cleaved to give (Z)-and (E)-1-alkylthio-5-benzyloxycarbonyl-6-methyl-2-phenylacetamido-4-aza-1,5-heptadien-3-one (13-16) or 2-benzyl-4-(3-benzyloxycarbonyl-4-methyl-1-oxo-2-aza-3-pentenyl)thiazole(17).

• Journal of Veterinary Clinics
• /
• v.27 no.2
• /
• pp.125-129
• /
• 2010

A 2-year-old female Pomeranian dog was referred with multiple pelvic fractures. The surgical correction was performed for the fractures. However, after the surgery, purulent exudation was occurred in the surgical site. Antibiotic susceptibility test revealed that the isolated bacteria are resistant to penicillins, cephalosporins, aminoglycosides, quinolones, and trimethoprim/sulfamethoxazole. Bacterial identification and extended-spectrum $\beta$-lactamase (ESBL) confirming test indicated that the isolated bacteriae is ESBL-producing Klebsiella pneumoniae. Minimum inhibitory concentration (MIC) and maximum bactericidal concentration (MBC) tests revealed that meropenem, one of carbapenems, is the only effective antibiotic. The patient was treated with meropenem for 5 days. After 10 days, the exudation was disappeared and the infection was cured. The molecular typing of the ESBL revealed that TEM-1 ESBL is present in the bacteria isolated from the patient. The bacteria isolated from the owner's palm also revealed that TEM-1 and SHV-1 ESBLs are present.

• Microbiology and Biotechnology Letters
• /
• v.34 no.4
• /
• pp.352-356
• /
• 2006

CW-270031, an injectable carbapenem, is a novel synthesized pyrrolidinyl-thio carbapenems. It was evaluated for its in vitro antibacterial activities in comparison with those of imipenem and meropenem against standard strains and clinical isolated strains, CW-270031 was more active than imipenem against gram-negative (E. coli and Klebsiella oxytoca) clinical isolates, but it was slightly active than meropenem. Against Klebsiella aeruginosa CW-118 MIC were 0.048 $\mu$g/ml for CW-270031, 0.19 $\mu$g/ml for imipenem. Against clinical E. coli MIC range were 0.012$\sim$0.195 $\mu$g/ml for CW-270031, 0.097$\sim$0.39 $\mu$g/ml for imipenem. Against clinical Klebsiella oxytoca MIC$_{50}$ were 0.09 $\mu$g/ml for CW-270031, 0.39 $\mu$g/ml for imipenem. Against gram-positive standard strains and clinical CW-270031 was slightly more activity than meropenem, but CW-270033 was less active than imipenem against these tested isolates. The subcutaneous injection of CW-270031 in mice revealed that the half-life of CW-270031 in serum was about 13 min, long than that of meropenem (10.6 min). CW-270031. was stable to hydrolysis by dog renal dehydropeptidase I (DHP-l) enzyme, to an more stabilities shown by meropenem.