Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal Function
The optimal regimens of cefmetazole and flomoxef for the treatment of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing <i>Enterobacterales</i> are not well defined. Our study found that the pharmacokinetic/pharmacodynamic targets for cefmetazole and flomo...
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MDPI AG
2022-03-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/4/456 |
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| author | Yukihiro Hamada Hidefumi Kasai Moeko Suzuki-Ito Yasufumi Matsumura Yohei Doi Kayoko Hayakawa |
| author_facet | Yukihiro Hamada Hidefumi Kasai Moeko Suzuki-Ito Yasufumi Matsumura Yohei Doi Kayoko Hayakawa |
| author_sort | Yukihiro Hamada |
| collection | DOAJ |
| description | The optimal regimens of cefmetazole and flomoxef for the treatment of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing <i>Enterobacterales</i> are not well defined. Our study found that the pharmacokinetic/pharmacodynamic targets for cefmetazole and flomoxef were 70% T > MIC, which is suggestive of bactericidal activity. A Monte Carlo simulation (MCS) was performed using the published data to calculate a new probability of target attainment (PTA ≥ 90%) for each renal function. The MCS was performed with 1000 replicates, and clinical breakpoints were calculated to attain PTA ≥ 90% for creatinine clearance (CCR) of 10, 30, 50, and 70 mL/min. The 90% ≥ PTA (70% T > MIC) of cefmetazole and flomoxef in patients who received a standard regimen (0.5 or 1 g, 1 h injection) for each renal function was calculated. Our results suggest that in patients with CCR of less than 30, 31–59, and more than 60 mL/min, the optimal dosage of cefmetazole would be 1 g q12 h, 1 g q8 h, and 1 g q6 h, respectively. Furthermore, in patients with CCR of less than 10, 10–50, and more than 50 mL/min, the optimal dosage of flomoxef would be 1 g q24 h, 1 g q8 h or 12 h, and 1 g q6 h, respectively. |
| first_indexed | 2024-03-09T11:14:55Z |
| format | Article |
| id | doaj.art-6114583edfb742c3b4323d837172a680 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T11:14:55Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-6114583edfb742c3b4323d837172a6802023-12-01T00:32:07ZengMDPI AGAntibiotics2079-63822022-03-0111445610.3390/antibiotics11040456Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal FunctionYukihiro Hamada0Hidefumi Kasai1Moeko Suzuki-Ito2Yasufumi Matsumura3Yohei Doi4Kayoko Hayakawa5Department of Pharmacy, Tokyo Women’s Medical University Hospital, Tokyo 162-8666, JapanSchool of Medicine, Keio University, Tokyo 160-8582, JapanDepartment of Pharmacy, Tokyo Women’s Medical University Hospital, Tokyo 162-8666, JapanDepartment of Clinical Laboratory Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, JapanCenter for Innovative Antimicrobial Therapy, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USADisease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo 162-8655, JapanThe optimal regimens of cefmetazole and flomoxef for the treatment of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing <i>Enterobacterales</i> are not well defined. Our study found that the pharmacokinetic/pharmacodynamic targets for cefmetazole and flomoxef were 70% T > MIC, which is suggestive of bactericidal activity. A Monte Carlo simulation (MCS) was performed using the published data to calculate a new probability of target attainment (PTA ≥ 90%) for each renal function. The MCS was performed with 1000 replicates, and clinical breakpoints were calculated to attain PTA ≥ 90% for creatinine clearance (CCR) of 10, 30, 50, and 70 mL/min. The 90% ≥ PTA (70% T > MIC) of cefmetazole and flomoxef in patients who received a standard regimen (0.5 or 1 g, 1 h injection) for each renal function was calculated. Our results suggest that in patients with CCR of less than 30, 31–59, and more than 60 mL/min, the optimal dosage of cefmetazole would be 1 g q12 h, 1 g q8 h, and 1 g q6 h, respectively. Furthermore, in patients with CCR of less than 10, 10–50, and more than 50 mL/min, the optimal dosage of flomoxef would be 1 g q24 h, 1 g q8 h or 12 h, and 1 g q6 h, respectively.https://www.mdpi.com/2079-6382/11/4/456antimicrobial stewardshipcefmetazoleflomoxefpharmacokinetics/pharmacodynamicsMonte Carlo simulations |
| spellingShingle | Yukihiro Hamada Hidefumi Kasai Moeko Suzuki-Ito Yasufumi Matsumura Yohei Doi Kayoko Hayakawa Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal Function Antibiotics antimicrobial stewardship cefmetazole flomoxef pharmacokinetics/pharmacodynamics Monte Carlo simulations |
| title | Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal Function |
| title_full | Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal Function |
| title_fullStr | Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal Function |
| title_full_unstemmed | Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal Function |
| title_short | Pharmacokinetic/Pharmacodynamic Analysis and Dose Optimization of Cefmetazole and Flomoxef against Extended-Spectrum β-Lactamase-Producing <i>Enterobacterales</i> in Patients with Invasive Urinary Tract Infection Considering Renal Function |
| title_sort | pharmacokinetic pharmacodynamic analysis and dose optimization of cefmetazole and flomoxef against extended spectrum β lactamase producing i enterobacterales i in patients with invasive urinary tract infection considering renal function |
| topic | antimicrobial stewardship cefmetazole flomoxef pharmacokinetics/pharmacodynamics Monte Carlo simulations |
| url | https://www.mdpi.com/2079-6382/11/4/456 |
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