Limited Postpartum Versus 24-Hour Antibiotic Dosing Regimens Following Intrapartum Chorioamnionitis [11A]

ABSTRACTSufficient antibiotic dosing in septic patients is essential for reducing mortality. Piperacillin-tazobactam is often used for empirical treatment, but due to the pharmacokinetic (PK) variability seen in septic patients, optimal dosing may be a challenge. We determined the PK profile for piperacillin given at 4 g every 8 h in 22 septic patients admitted to a medical ward. Piperacillin concentrations were compared to the clinical breakpoint MIC forPseudomonas aeruginosa(16 mg/liter), and the following PK/pharmacodynamic (PD) targets were evaluated: the percentage of the dosing interval that the free drug concentration is maintained above the MIC (fTMIC) of 50% and 100%. A two-compartment population PK model described the data well, with clearance being divided into renal and nonrenal components. The renal component was proportional to the estimated creatinine clearance (eCLCR) and constituted 74% of the total clearance in a typical individual (eCLCR, 83.9 ml/min). Patients with a high eCLCR(>130 ml/min) were at risk of subtherapeutic concentrations for the current regimen, with a 90% probability of target attainment being reached at MICs of 2.0 (50%fTMIC) and 0.125 mg/liter (100%fTMIC). Simulations of alternative dosing regimens and modes of administration showed that dose increment and prolonged infusion increased the chance of achieving predefined PK/PD targets. Alternative dosing strategies may therefore be needed to optimize piperacillin exposure in septic patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02569086.)

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Antibiotic dosing regimens for septic patients receiving continuous venovenous haemofiltration: do current studies supply sufficient data?

Critical Care ◽

10.1186/cc7439 ◽

2009 ◽

Vol 13 (Suppl 1) ◽

pp. P275

Author(s):

A Li ◽

C Gomersall ◽

G Choi ◽

Q Tian ◽

G Joynt ◽

...

Keyword(s):

Sufficient Data ◽

Continuous Venovenous Haemofiltration ◽

Dosing Regimens ◽

Antibiotic Dosing

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Comparing Clinical Outcomes of Piperacillin-Tazobactam Administration and Dosage Strategies in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis

10.21203/rs.2.24493/v1 ◽

2020 ◽

Author(s):

Sarah Fawaz ◽

Stephen Barton ◽

Shereen Nabhani-Gebara

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Intermittent Infusion ◽

Adult Patients ◽

Prolonged Infusion ◽

Dosing Regimens ◽

Meta Analyses ◽

Antibiotic Dosing

Abstract Background: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically-ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Methods: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Results: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (OR 1.56, 95% C.I 1.28-1.90, P = 0 .0001), lower mortality rates (OR 0.68, 95% C.I 0.55-0.84, P = 0 .0003), higher microbiological success rates (OR 1.52, 95% C.I 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (OR -1.27, 95% C.I -2.45—0.08, P = 0.04) in critically ill patients. Conclusion: There is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. Therefore, this alternative infusion strategy could be recommended in clinical practice.

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Comparing Clinical Outcomes of Piperacillin-Tazobactam Administration and Dosage Strategies in Critically Ill Adult Patients: A Systematic Review and Meta-Analysis

10.21203/rs.2.24493/v2 ◽

2020 ◽

Author(s):

Sarah Fawaz ◽

Stephen Barton ◽

Shereen Nabhani-Gebara

Keyword(s):

Confidence Interval ◽

Critically Ill ◽

Critically Ill Patients ◽

Odds Ratio ◽

Intermittent Infusion ◽

Prolonged Infusion ◽

Level Of Evidence ◽

Dosing Regimens ◽

Meta Analyses ◽

Antibiotic Dosing

Abstract Background: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Methods: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Results: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (Odds Ratio 1.56, 95% Confidence Interval 1.28-1.90, P = 0 .0001), lower mortality rates (Odds Ratio 0.68, 95% Confidence Interval 0.55-0.84, P = 0 .0003), higher microbiological success rates (Odds Ratio 1.52, 95% Confidence Interval 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (Odds Ratio -1.27, 95% Confidence Interval -2.45—0.08, P = 0.04) in critically ill patients.Conclusion: Results from this study show that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. However, more rigorous scientific studies in critically ill patients are warranted to reach a sufficient level of evidence and promote further implementation of C/PI as a dosing strategy.

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Augmented Renal Clearance and How to Augment Antibiotic Dosing

Antibiotics ◽

10.3390/antibiotics9070393 ◽

2020 ◽

Vol 9 (7) ◽

pp. 393

Author(s):

Iris H. Chen ◽

David P. Nicolau

Keyword(s):

Renal Clearance ◽

Critically Ill ◽

Clinical Failure ◽

Augmented Renal Clearance ◽

The Past ◽

Dosing Regimens ◽

Natural Response ◽

Serious Disease ◽

Pharmacologic Therapies ◽

Antibiotic Dosing

Augmented renal clearance (ARC) refers to the state of heightened renal filtration commonly observed in the critically ill. Its prevalence in this patient population is a consequence of the body’s natural response to serious disease, as well as the administration of fluids and pharmacologic therapies necessary to maintain sufficient blood pressure. ARC is objectively defined as a creatinine clearance of more than 130 mL/min/1.73 m2 and is thus a crucial condition to consider when administering antibiotics, many of which are cleared renally. Using conventional dosing regimens risks the possibility of subtherapeutic concentrations or clinical failure. Over the past decade, research has been conducted in patients with ARC who received a number of antibacterials frequently used in the critically ill, such as piperacillin-tazobactam or vancomycin. Strategies to contend with this condition have also been explored, though further investigations remain necessary.

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AUIC — A General Target for the Optimization of Dosing Regimens of Antibiotics?

Annals of Pharmacotherapy ◽

10.1177/106002809603000919 ◽

1996 ◽

Vol 30 (9) ◽

pp. 1024-1028 ◽

Cited By ~ 20

Author(s):

Teresa Dalla Costa ◽

Hartmut Derendorf

Keyword(s):

Minimum Inhibitory Concentration ◽

Inhibitory Concentration ◽

Systematic Evaluation ◽

Concentration Profiles ◽

Beta Lactams ◽

Dosing Schedule ◽

Dosing Interval ◽

Dosing Regimens ◽

Specific Equation ◽

Antibiotic Dosing

OBJECTIVE: To present a systematic evaluation of the area under the inhibitory curve (AUIC) approach for the optimization of antibiotic dosing schedules for three major antibiotic classes (beta-lactams, quinolones, aminoglycosides). It has been proposed that an AUIC over 24 hours of at least 125 may be an applicable target parameter for the optimization of antibiotic dosing schedules across these antibiotic classes. Some limitations of this approach are presented and discussed. METHODS: A precise equation for the calculation of AUIC is derived. Moreover, a specific equation is derived for the situation that results in a trough concentration at the end of the dosing interval equal to the minimum inhibitory concentration (MIC). With the same three drags used for deriving the target AUIC value (tobramycin, cefmenoxime, ciprofloxacin), different dosing regimens are simulated to obtain the target AUIC of 125. RESULTS: Very different serum concentration profiles can result in the same AUIC. In an example for cefmenoxime, dosing regimens of 1 g q6h and 4.2 g q24h resulted in equal AUIC values of 125, whereas the respective time above MIC differed dramatically (99% of the dosing interval for q6h vs. 36% for q24h). CONCLUSIONS: It does not seem valid to accept the proposed breakpoint AUIC target of at least 125 as an applicable value for determining the appropriate dosing schedule of these classes of antibiotics. Based on the limitations discussed about the AUIC approach, the same conclusion also holds for any other fixed AUIC breakpoint target value.

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