PMID- 34262257
OWN - NLM
STAT- MEDLINE
DCOM- 20211208
LR  - 20220424
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 15
DP  - 2021
TI  - Evaluation of Ceftazidime/Avibactam Administration in Enterobacteriaceae and 
      Pseudomonas aeruginosa Bloodstream Infections by Monte Carlo Simulation.
PG  - 2899-2905
LID - 10.2147/DDDT.S309825 [doi]
AB  - PURPOSE: To evaluate the administration regimen of ceftazidime/avibactam (CZA) 
      for bloodstream infections caused by Enterobacteriaceae and Pseudomonas 
      aeruginosa. METHODS: The minimal inhibitory concentrations (MICs) of CZA against 
      Enterobacteriaceae and P. aeruginosa isolated from blood cultures at member 
      hospitals in BRICS (Blood Bacterial Resistant Investigation Collaborative System) 
      in 2019 were determined by broth micro-dilution methodology. A 10,000-patient 
      Monte Carlo simulation (MCS) was used to calculate the probability of target 
      attainment (PTA) and cumulative fraction of response (CFR) for different CZA 
      dosage regimens to evaluate their efficacies and optimize the best initial dosage 
      regimen. RESULTS: Altogether, 6487 Enterobacteriaceae and P. aeruginosa strains 
      were isolated from the blood cultures. The overall CZA resistance rate was 2.31%, 
      of which the Enterobacteriaceae and P. aeruginosa rates were 1.57% and 14.29%, 
      respectively. The MCS showed that the greater the MIC value, the worse the 
      therapeutic effect. When the CZA MIC was </=8 mg/L, the standard dose (2.5g iv q8h) 
      achieved 90% PTA in the subset of patients with creatinine clearance (CrCl) 
      values from 51 to 120 mL/min. Although the high-dose regimen (3.75g iv q8h) 
      achieved 90% PTA in patients with CrCl values from 121 to 190 mL/min, 
      implementing the low-dose regimen (1.25g iv q8h) was also effective for patients 
      in the 51-89 mL/min CrCl range. Generally, the high-dose regimen (3.75g iv q8h) 
      reached 90% CFR against all of the strains. Conversely, in patients with CrCl 
      values of 121-190 mL/min, the standard dose (2.5g iv q8h) failed to reach 90% CFR 
      against some Enterobacteriaceae members and P. aeruginosa. When the dose was 
      reduced to the low-dose regimen (1.25g iv q8h), no patients reached 90% CFR 
      against some Enterobacteriaceae members and P. aeruginosa. CONCLUSION: CZA has 
      good antibacterial activity against Enterobacteriaceae and P. aeruginosa in 
      bloodstream infections. Clinicians could make individualized treatment regimens 
      in accordance with the sensitivity of the strains and the level of renal function 
      in their patients to best predict the drug-related clinical responses.
CI  - (c) 2021 Dai et al.
FAU - Dai, Yuanyuan
AU  - Dai Y
AD  - Department of Laboratory, First Affiliated Hospital of University of Science and 
      Technology of China, Hefei, People's Republic of China.
FAU - Chang, Wenjiao
AU  - Chang W
AD  - Department of Laboratory, First Affiliated Hospital of University of Science and 
      Technology of China, Hefei, People's Republic of China.
FAU - Zhou, Xin
AU  - Zhou X
AD  - Department of Laboratory, First Affiliated Hospital of University of Science and 
      Technology of China, Hefei, People's Republic of China.
FAU - Yu, Wei
AU  - Yu W
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Huang, Chen
AU  - Huang C
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Chen, Yunbo
AU  - Chen Y
AUID- ORCID: 0000-0002-5843-1386
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Ma, Xiaoling
AU  - Ma X
AD  - Department of Laboratory, First Affiliated Hospital of University of Science and 
      Technology of China, Hefei, People's Republic of China.
FAU - Lu, Huaiwei
AU  - Lu H
AD  - Department of Laboratory, First Affiliated Hospital of University of Science and 
      Technology of China, Hefei, People's Republic of China.
FAU - Ji, Rujin
AU  - Ji R
AUID- ORCID: 0000-0003-1579-2250
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Ying, Chaoqun
AU  - Ying C
AUID- ORCID: 0000-0001-8599-3838
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Wang, Peipei
AU  - Wang P
AUID- ORCID: 0000-0002-5873-8732
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Liu, Zhiying
AU  - Liu Z
AUID- ORCID: 0000-0002-2060-1597
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
FAU - Yuan, Qingfeng
AU  - Yuan Q
AD  - Department of Laboratory, First Affiliated Hospital of University of Science and 
      Technology of China, Hefei, People's Republic of China.
FAU - Xiao, Yonghong
AU  - Xiao Y
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 
      Clinical Research Center for Infectious Diseases, Collaborative Innovation Center 
      for Diagnosis and Treatment of Infectious Diseases, Zhejiang Provincial Key 
      Laboratory for Drug Clinical Research and Evaluation, The First Affiliated 
      Hospital, Zhejiang University, Hangzhou, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210706
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Azabicyclo Compounds)
RN  - 0 (Drug Combinations)
RN  - 0 (avibactam, ceftazidime drug combination)
RN  - 9M416Z9QNR (Ceftazidime)
SB  - IM
MH  - Anti-Bacterial Agents/*administration & dosage/pharmacology
MH  - Azabicyclo Compounds/*administration & dosage/pharmacology
MH  - Bacteremia/drug therapy/microbiology
MH  - Ceftazidime/*administration & dosage/pharmacology
MH  - Computer Simulation
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Drug Resistance, Bacterial
MH  - Enterobacteriaceae/drug effects/isolation & purification
MH  - Enterobacteriaceae Infections/*drug therapy/microbiology
MH  - Humans
MH  - Microbial Sensitivity Tests
MH  - Monte Carlo Method
MH  - Pseudomonas Infections/*drug therapy/microbiology
MH  - Pseudomonas aeruginosa/drug effects/isolation & purification
PMC - PMC8275101
OTO - NOTNLM
OT  - Gram-negative bacteria
OT  - dosage regimens
OT  - extended-spectrum beta-lactamase
OT  - minimum inhibitory concentration
OT  - pharmacodynamics
OT  - pharmacokinetics
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/07/16 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/07/06
CRDT- 2021/07/15 06:16
PHST- 2021/03/10 00:00 [received]
PHST- 2021/05/20 00:00 [accepted]
PHST- 2021/07/15 06:16 [entrez]
PHST- 2021/07/16 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/07/06 00:00 [pmc-release]
AID - 309825 [pii]
AID - 10.2147/DDDT.S309825 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2021 Jul 6;15:2899-2905. doi: 10.2147/DDDT.S309825. 
      eCollection 2021.