• Korean Journal of Clinical Pharmacy
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• v.22 no.3
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• pp.234-238
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• 2012

Background: Valproic acid is widely used in the treatment of generalized tonic-clonic and partial seizures. The carbapenem class is the most potent and widest spectrum of antimicrobial activity. Concomitant administration of carbapenems and valproic acid has been reported to decrease the serum concentration of valproic acid, which is sometimes associated with seizures. The purpose of this study is to evaluate the changes in valproic acid concentration and half life and the frequency of seizure during concomitant administration of valproic acid and carbapenems. Method: This study was performed retrospectively on total 40 cases with identified valproic acid concentration during concomitant administration of valproic acid and carbapenems at Kangbuk Samsung Hospital from February 1st, 2006 to October 31st, 2011. Patients were classified into 3 groups: ertapenem group (n=14), imipenem group (n=12), meropenem group (n=14). Results: The mean serum concentrations in each group during combined treatment were $9.50{\pm}8.84$, $21.88{\pm}8.17$ and $10.62{\pm}8.67$ mg/L, respectively (p < 0.001). The mean half-lives in each group during concurrent use of valproic acid and carbapenems were $3.18{\pm}0.81$, $4.63{\pm}1.97$ and $2.67{\pm}1.69$ hr, respectively (p < 0.001). The valproic acid serum concentration decreased by 75.5%, 54.1% and 84.1% and the half-life of valporoic acid decreased by 65.6%, 35.7% and 73.5%, respectively. Total cases with seizure were 12(30%) with 5(35.7%) in the ertapenem group, 3 (25.0%) in the imipenem group and 4(28.6%) in the meropenem group (p=0.911). There were no specific factors to influence on seizure development during combined treatment. Conclusion: Concurrent use of carbapenems and valproic acid should be avoided. If concomitant administration is essential, very close serum concentration monitoring and clinical observation are necessary.

• Bulletin of the Korean Chemical Society
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• v.22 no.6
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• pp.553-558
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• 2001

A stereoselective synthesis of $1\beta-aminocarbapenems$ (11a-c) starting from-4-acetoxy-2-axetidinone derivative 4 is described. 4-Acetoxy-2-azetidinone derivative (4) was reacted with lithium enolate of benzophenone limine of glycine phenyl ester (5f) to give alkylated product (R)-6f in good yield with high diastereoselectivity. The alkylated procudt (R)-6f was transformed to thioesters (7a-c) by transesterification with thiols, Thioesters (7a-c) were converted to their oxalimides (8a-c), followed by the phosphite-mediated reductive cyclization to give carbapenems (9a-c). Removal of all protecting groups of carbapenems (9a-c) afforded $1\beta-aminocarbapenems$ (11a-c).

• Bulletin of the Korean Chemical Society
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• v.7 no.5
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• pp.405-407
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• 1986

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.179.3-180
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• 2002

• Bulletin of the Korean Chemical Society
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• v.8 no.2
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• pp.130-132
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• 1987

• Bulletin of the Korean Chemical Society
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• v.7 no.4
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• pp.325-327
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• 1986

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.34-35
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• 1993

The Development of new asymmetric induction methods useful for syntheses of biologically active natural products and drugs, using C4-chiral 1,3-th-iazolidine-2-thiones, has been a recent focus of interest. 1-8) The present account describes the significance of particular heterocycles in the synthetic development of new 1${\beta}$-substituted carbapenems. A fungal metabolite, (＋)-thienamycin (1) has attracted one's attention as a hopeful candidate for new-generation antibiotic drugs because of its strong antimicrobial activities and wide antimicrobial spectra due to the extensive inhibition against various ${\beta}$-lactamases. However, it has been serious problems toward a practically useful drug that (＋)-thienamycin is fairly labile in the solution and can be metabolized by renal dehydropept- idase-I (DHP-I). Recently, a Merck Sharp ＆ Dohme research group exploited a non-natural ${\beta}$-lactam, imipenem (2) which has been appeared in the drug market as the first carbapenem-type antibiotic drug. 9) However 2 must be used with a DHP-I inhibitor, cilastatin sodium (3).9) Thus, a 1,${\beta}$-methyl- carbapenem derivative 4 has been disclosed by the same group. 10) It seems to be more hopeful candidate as a new-generation antibiotic because it can directly resist against metabolism by the renal DHP-1 without an enzyme inhibitor 3. 10)

• The Korean Journal of Medicine
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• v.99 no.3
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• pp.149-157
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• 2024

Background/Aims: Carbapenems are recommended for treating bacteremia caused by extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae (ESBL-E). However, this has resulted in a significant rise in the utilization of carbapenems in cases of ESBL-E infection. We evaluated the clinical outcomes of patients with ESBL-E bacteremia treated with non-carbapenem antimicrobials. Methods: We conducted a retrospective case-control study of a cohort of patients with documented ESBL-E bacteremia from January 2021 to December 2021. The patients were divided into two groups according to whether they received non-carbapenem or carbapenem therapy. The rates of treatment failure, 30-day mortality and microbiologic failure, and the durations of hospitalization and of antimicrobial therapy were compared between the two groups. Antimicrobial susceptibility testing and phenotypic identification of ESBL-E were performed using the Vitek 2 system. Results: Of 118 patients with ESBL-E bacteremia, 54 received non-carbapenem drugs (non-carbapenem group [NCG]) and 64 received carbapenems (carbapenem group [CG]). Treatment failure at 30 days occurred in 16.7% of the patients in the NCG and in 18.8% in the CG (p = 0.65). The 30-day mortality rate was 14.8% in the NCG and 17.2% in the CG (p = 0.63). Extra-urinary tract infection and prior antimicrobial therapy within 30 days were risk factors for treatment failure in patients with ESBL-E bacteremia. The clinical outcomes did not differ significantly between the two groups, challenging the prevailing preference for carbapenems in the treatment of ESBL-E bacteremia. Conclusions: Non-carbapenem antimicrobials such as piperacillin/tazobactam are recommended for patients with mild ESBL-E bacteremia in South Korea.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.167.3-168
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• 2000

• Journal of the Korean Chemical Society
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• v.30 no.1
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• pp.138-142
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• 1986