• 약학회지
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• 제37권3호
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• pp.295-305
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• 1993

In order to develop oral cephalosporin having a new substituent at 3 position, the synthesis of cephalosporins modified at C-3 and the effect of the substituents on the oral absorption is studied. 7-[(Z)-2-(2-Aminothiazole- 4-yl)-2-methoxyiminoacetamidol-3-[4-(2-pyridyl )piperazinyl] thiocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN1) and 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimid yl)piperazinylthiocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN2) were synthesized from 4-(2-piridyl)piperazinyl dithiocarbamate potassium salt or 4-(2-pirimidyl)piperazinyl dithiocarbamate potassium salt and cefotaxime. Also pivaloyloxymethyl esters of CEN1 and CEN2, pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl )piperazinyllthiocarbonylthiomethyl-3-cephem-4-carboxylate (CENIP) and pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamidol-3- [4-(2-pyrimid yl)piperazinyllthiocarbonylthiomethyl-3-cephem-4-carboxylate (CEN2P) were synthesized. The in vitro activities of two new oral cephalosporins, CEN1 and CEN2, were compared with the in vitro activities of cefaclor and cefotaxime against a variety of bacterial species. CEN2 has a broad antibacterial spectrum covering Gram-positive and Gram-negative bacteria, similar to that exhibited by CEN1 and cefotaxime. CEN1 and CEN2 were more active in vitro than cefaclor against Streptococcus pyogenes, Klebsiella aerogenes and Enterobacter cloacae.

• 약학회지
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• 제38권2호
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• pp.123-130
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• 1994

Physicochemical properties and hydrolysis kinetics of new some oral cephalosporins were examined in buttered solution and human plasma or rat liver homogenate. The test cephalosporins were 7-[(Z)-2-(2-aminothiazole-4-yl)-2- methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl] thiocarbonylthhiomethyl-3-cephem-4-carboxylic acid (CEN1), 7-[(Z)-2-(2-aminoth iazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyl]th iocarbonylthiomethyl-3-cephem-4-carboxylic acid (CEN2), pivaloyloxymethyl-7-[ (Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazi nyl]thiocarbonylthiomethy1-3-cephem-4-carboxylate (CEN1P), and pivaloyloxymethyl-7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[ 4-(2-pyrimidyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate (CEN2P). The partition coefficient(Ko/w) of CEN1P, CEN2P were higher than those of CEN1, CEN2. The calculated pKa values of CEN1, CEN2, CEN1P, and CEN2P were 7.09, 7.75, 4.92, and 5.39, respectively. The hydrolysis of CEN1P and CEN2P were not depend on the composition of pH of the test medium except weak alkaline buffered solution (pH 8.00). CEN1 and CEN2 were very stable in pH 6.80 and 8.00 buffer solutions. CEN1P and CEN2P were rapidly deesterified to CEN1 and CEN2 in human plasma and in rat liver homogenate. Half-lives$(t_{1/2})$ of CEN1 and CEN2 were 3.49 and 4.93 hr in human plasma, 1.47 and 1.26 hr in rat liver homogenate, respectively.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.83-88
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• 2003

KR-984055 is a new oral cephalosporin antibiotic with activity against both gram-positive and gram-negative bacteria. Lipophilic ester-type prodrugs of KR-984055, i.e., KR-999001 and KR-999002, have been synthesized in an attempt to increase the oral bioavailability of this broad-spectrum antibiotic agent. In this study we determined the oral bioavailability of KR-984055 and its prodrugs in the rat, and evaluated the pharmacokinetic model that best describes the plasma concentration behavior following single intravenous (IV) and oral single dose. In addition, concentrations in plasma as well as biliary and urinary recovery of KR-984055 were determined. Also, protein binding of KR-984055 in plasma was examined in vitro. The degree of protein binding of KR-984055 was in the range of 92.09~94.77%. KR-984055 exhibited poor oral bioavailability (7.02$\pm$1.58%). The observed oral bioavailabilities of KR-984055 from KR-999001 and KR-999002 were 38.77$\pm$2.81 % and 39.81$\pm$5.25%, respectively. These data were calculated from the levels of free KR-984055 in plasma. Oral KR-999001 and KR-999002 were not recovered from plasma, suggesting that it was readily cleaved to free KR-984055. KR-999001 and KR-999002 appear to be an efficient oral prod rug of KR-984055 that deserved further clinical evaluation in human.

• 한국임상약학회지
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• 제20권2호
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• pp.145-150
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• 2010

In order to investigate the antibiotic prescription pattern for upper respiratory infections (URI), the prescription sheets for outpatients from July 2008 to June 2009 were collected from 7 community pharmacies in Ulsan City, and the prescription pattern of Pediatric and ENT physicians was analyzed. The antibiotic prescription rates of Pediatric and ENT physicians were 63.8% and 61.7%, respectively. It was also observed that the oral antibiotic prescription was 95.6% in Pediatrics and 97.6% in ENT. The most favorable antibiotics by Pediatric physicians were penicillins (21.5%) penicillin-clavulanate (36.4%) and cephalosporins (16.5%), macrolides (11.6%), quinolones (3.5%), and nifuroxazide (3.5%). In case of ENT, the commonly prescribed antibiotics were also penicillin-clavulanate (47.6%), cephalosporins (31.6%), macrolides (11.9%) and sulfonamide (1.3%). The antibiotic combination rate was 7.6% in Peditrics and 1.9% in ENT, among antibiotic prescriptions. The combination of more than two oral antibiotics was examined as 66.8% in Pediatrics and 44.2% in ENT. The common oral antibiotic combination in Pediatrics was prescriptions of two ${\beta}$-lactam antibiotics (54.3%). Among them 83% was the combination of amoxicillin-clavulanate (7:1) and amoxicillin, which could be judged as antibiotic overuse. The next highly prescribed oral antibiotic combination was ${\beta}$-lactam/macrolide antibiotic combination probably for URI (11.3%) and ${\beta}$-lactam/nifuroxazide combination (10.0%) presumably for acute diarrhea. Comparatively the oral antibiotic combination prescribed by ENT physicians was negligible except one physician. In conclusion, the antibiotic over-prescription rate by antibiotic combination was much higher in Pediatrics than ENT, even though both clinical departments showed nealy the similar antibiotic prescription rates.

• 약학회지
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• 제38권2호
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• pp.140-148
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• 1994

${\beta}-Lactamase$ stability, chemotherapeutic activity, and pharmacokinetics of 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN1), 7-[(Z)-2-(2-aminothiazole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyrimidyl)piperazinyl]thiocarbonylthiomethyl-3-cephem-4-carboxylic acid(CEN2), pivaloyloxymethyl-7-[(Z)-2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN1P), and pivaloyloxymethyl-7-{(Z)--2-(2-aminothizaole-4-yl)-2-methoxyiminoacetamido]-3-[4-(2-pyridyl)piperazinyl]thiocarbonyl-thiomethyl-3-cephem-4-carboxylate(CEN2P) were examined. CEN1, CEN2, CEN1P, and CEN2P were very stable to the ${\beta}-lactamase$ obtained from three strains(Enterobacter cloacae P99, Escherichia coli TEM, and Citrobacter freundii). Chemotherapeutic activities$(ED_{50})$ of CEN2 and CEN2P against experimental systemic infections due to Streptococcus pyogenes 77A and Escherichia coli 078 were superior to those of CEN1 and CEN1P, respectively. The $ED_{50}$ values of CEN1, CEN2 were 5.82 mg/kg, 0.89 mg/kg(s.c., S. pyogenes 77A) while those of CEN1P, CEN2P were 14.56mg/kg, 6.40mg/kg(p.o., S. pyogenes 77A), respectively. The pharmacokinetics of CEN1, CEN2, CEN1P, and CEN2P were investigated in mice and rats. In mice, peak blood levels of $1.25\;{\mu}g/ml$ were recorded within 20 min after oral administration of a single dose equivalent to 40 mg/kg CEN1P. Cmax of CEN1P was much higher than that of CEN1 in mice and rats. Oral absorption of CEN2P was much higher than that of CEN2.

• Archives of Pharmacal Research
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• 제21권5호
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• pp.559-564
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• 1998

Preparation and biological activity of prodrug-type 3-methoxymethyl cephalosporins were described. From the mixtures, R- and S-prodrugs were separated and their absolute configurations were determined, and also their bioavailability was investigated.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제49권4호
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• pp.198-207
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• 2023

Objectives: This study investigated causative strains and their antibiotic sensitivity in patients who were hospitalized for maxillofacial odontogenic infections at a tertiary center in South Korea over the past 10 years with the aim of providing guidelines for the selection of appropriate empirical antibiotics. Materials and Methods: Patients with head and neck fascial space abscesses due to odontogenic infections who underwent incision and drainage surgery with pus culture tests between 2013 and 2022 at the Department of Oral and Maxillofacial Surgery, Dankook University Hospital were included. The bacterial isolates and antibiotic sensitivity of each strain were analyzed for 2013-2022, 2013-2017, and 2018-2022. The affected fascial spaces were classified into primary, secondary, and deep neck spaces. Results: In the 192 patients included in this study, 302 strains were detected. Viridans streptococcus had the highest frequency (51.7%), followed by Prevotella spp. (16.9%), Staphylococcus spp. (5.6%), and Klebsiella pneumoniae (4.6%). The identification rate of viridans streptococcus significantly increased from 41.8% in 2013-2017 to 60.9% in 2018-2022. Viridans streptococcus showed an antibiotic sensitivity of 80.5% to ampicillin; the sensitivity to penicillin antibiotics decreased over the study period. Antibiotic susceptibility was approximately 94% for third-generation cephalosporins. K. pneumoniae, which was identified at a high percentage in patients with deep neck space infection, showed increasing antibiotic resistance to most antibiotics over the study period. Conclusion: Viridans streptococcus was identified in head and neck fascial space abscesses with the highest frequency. Empirical antibiotics should be effective against this strain; penicillin antibiotics are considered inappropriate. For effective treatment of deep neck space abscesses, bacterial culture and antibiotic sensitivity tests performed as soon as possible are essential.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제46권1호
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• pp.49-57
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• 2020

Objectives: This study aimed to understand the nationwide patterns of antibiotic prescription after tooth extraction in adult patients. Materials and Methods: This study analyzed dental records from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database on 503,725 tooth extractions performed in adults (≥19 years) during 2011-2015. Patient sex, age, household income, systemic disease (diabetes mellitus and hypertension), type of dental institution, region of dental institution, year of prescription, and type of tooth extraction procedure were considered. The antibiotic prescription rate and broad-spectrum antibiotic prescription frequency were analyzed using chi-squared tests. Factors affecting the prescription of broad-spectrum antibiotics were evaluated using multivariate logistic regression analysis. Results: The rate of antibiotic prescription after tooth extraction was 81.85%. Penicillin was most commonly prescribed (45.25%), followed by penicillin with beta-lactamase inhibitors (18.76%), metronidazole (12.29%), and second- to fourth-generation cephalosporins (11.52%). The proportion of broad-spectrum antibiotics used among all prescribed antibiotics was 45.88%. Conclusion: The findings of this study demonstrate that the rate of antibiotic prescription after tooth extraction is higher in Korea than in other countries. Furthermore, broad-spectrum antibiotics are used more frequently, which may indicate unnecessary drug prescription, an important contributor to antibiotic resistance.

• Journal of Chest Surgery
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• 제19권1호
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• pp.174-179
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• 1986

Augmentin is a formulation of amoxycillin trihydrate and potassium clavulanate, a fused beta-lactam molecule produced by the fermentation of Streptomyces clavuligerus. Most clinically important resistance is due to the production by bacteria of antibiotic destroying enzymes. In the case of penicillins and cephalosporins these enzymes are termed beta-lactamase as they destroy the beta-lectern ring of these antibiotics, completely inactivating them. The presence of clavulanic acid extends the spectrum of amoxycillin to include bet On clinical study of the intravenous Augmentin in the field of thoracic and cardiovascular surgical cases, we selected randomly 30 patients, 21 male and 9 female, age from 13 to 72, in the period from April to December 1985. Among the total 30 patients, 22 were preoperatively infected [11 thoracic empyema, 5 lobar pneumonia, 2 lung abscess, 2 bronchiectasis, one acute pyelonephritis with ureter stone and one rheumatic carditis], and 8 were not infected preoperatively [Table 1, 2]. Of the preoperatively infected group, 11 cases [50%] were culture positive [4 staphylococcus, 3 pseudomonas, 2 Serratia group, and one E. coli], and preoperatively non-infected group [8 cases] revealed expectedly negative findings on bacterial culture. All of the culture positive bacteria were sensitive to Augmentin on disc culture sensitivity test except one case of E. coli. Daily doses of intravenous Augmentin were 2.-1-6.0gm divided in 2-5 injections. Every injection administered [1.2gm at Augmentin dissolved in 20ml distilled water] slowly for more than 20 minutes. Duration of injection was variable according to the clinical conditions from minimum 5 to maximum 31 days. The results of antibiotic treatment with Augmentin and some other antibiotic combinations pre- and postoperatively were subgrouped as EXCELLENT, EFFECTIVE, and FAILURE. Clinical criteria of the therapeutic result were symptomatic, objective and laboratory improvement. 8 cases were excellent, 13 effective, and one failure among the preoperatively infected group, and all 8 cases of the preoperatively non-infected group were effective as pro;hylactive antibiotic therapy. Overall effective ratio was 97% in both subgroup. There was no side effect clinically and laboratory study including liver and kidney function test during and after the I.V. administration of Augmentin. Oral swallow tablets which were administered after discharge from hospital also revealed good effects with some degree of gastrointestinal trouble.

• Clinical and Experimental Pediatrics
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• 제49권7호
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• pp.777-783
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• 2006

목 적 : 최근 소아 요로감염의 가장 흔한 원인균인 E. coli에 대한 항생제 내성 문제가 점차 대두되고 있다. 본 연구에서는 소아 원외 요로감염 환아에서 분리된 E. coli에 대한 cefixime을 포함하여 흔히 사용되고 있는 경구용 항생제의 시험관 내 감수성 연구를 시행하여 적합한 치료 항생제 선택의 기초 자료를 얻고자 하였다. 방 법 : 2004년 10월부터 2005년 9월까지 연구 참여 병원 소아과 외래에서 요로감염으로 진단된 206명 환아의 요 배양검사에서 동정된 211개 균주 중 188개 E. coli를 대상으로 경구용 항생제(ampicillin, amoxillin, ampicillin-sulbactam, cefaclor, TMP-SMX, cefixime)에 대한 시험관 내 감수성 검사를 실시하였다. 결 과 : 분리된 E. coli 균주에 대한 항생제별 감수성 결과에서 내성률은 각각 ampicillin 81.4%, amoxicillin 85.6%, ampicillin-Sulbactam 77.2%, cefaclor 93.6%, TMP-SMX 50.5%, cefixime 13.3%이었다. ESBL 생성 E. coli는 7.0%이었다. 결 론 : Aminopenicillins계, cefaclor, sulfa약제들은 E. coli에 대한 내성률이 매우 높아 소아 요로감염의 일차 선택 항생제로 유용하지 못한 것으로 추정할 수 있었다. 그러나 cefixime과 같은 3세대 cephalosporin은 일차 치료 실패할 경우 이차 선택항생제로 유용할 수 있으며, 일차 선택 항생제로도 사용될 수 있을 것으로 추정되었다. E. coli의 항생제 내성 양상에 대한 광범위한 연구와 지속적 감시를 통하여 소아 원외 요로감염 치료에서 1차적으로 선택될 수 있는 경구용 항생제에 대한 지침 자료가 요구된다.