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JAMA Oct 2023Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been...
IMPORTANCE
Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.
OBJECTIVE
To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.
DESIGN, SETTING, AND PARTICIPANTS
The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.
INTERVENTIONS
Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.
MAIN OUTCOMES AND MEASURES
The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.
RESULTS
There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).
CONCLUSIONS AND RELEVANCE
Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05094154.
Topics: Humans; Adult; Female; Middle Aged; Male; Anti-Bacterial Agents; Cefepime; Coma; Piperacillin; Drug Therapy, Combination; Retrospective Studies; Piperacillin, Tazobactam Drug Combination; Sepsis; Acute Kidney Injury; Kidney; Delirium
PubMed: 37837651
DOI: 10.1001/jama.2023.20583 -
JAMA Sep 2018Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial.
IMPORTANCE
Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.
OBJECTIVES
To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.
DESIGN, SETTING, AND PARTICIPANTS
Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.
INTERVENTIONS
Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.
RESULTS
Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.
CONCLUSIONS AND RELEVANCE
Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.
TRIAL REGISTRATION
anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.
Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cause of Death; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins
PubMed: 30208454
DOI: 10.1001/jama.2018.12163 -
Clinical Pharmacology and Therapeutics Sep 2017Vancomycin use is often associated with nephrotoxicity. It remains uncertain, however, to what extent vancomycin is directly responsible, as numerous potential risk... (Review)
Review
Vancomycin use is often associated with nephrotoxicity. It remains uncertain, however, to what extent vancomycin is directly responsible, as numerous potential risk factors for acute kidney injury frequently coexist. Herein, we critically examine available data in adult patients pertinent to this question. We review the pharmacokinetics/pharmacodynamics of vancomycin metabolism. Efficacy and safety data are discussed. The pathophysiology of vancomycin nephrotoxicity is considered. Risk factors for nephrotoxicity are enumerated, including the potential synergistic nephrotoxicity of vancomycin and piperacillin-tazobactam. Suggestions for clinical practice and future research are given.
Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Humans; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Vancomycin
PubMed: 28474732
DOI: 10.1002/cpt.726 -
JAMA May 2023Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of...
IMPORTANCE
Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood.
OBJECTIVE
To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics.
DESIGN, SETTING, AND PARTICIPANTS
Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment.
INTERVENTION
The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care).
MAIN OUTCOMES AND MEASURES
The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program.
RESULTS
The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32).
CONCLUSIONS AND RELEVANCE
In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03269994.
Topics: Male; Adult; Humans; Aged; Cefoxitin; Piperacillin; Pancreaticoduodenectomy; Pancreatic Fistula; Penicillanic Acid; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Sepsis
PubMed: 37078771
DOI: 10.1001/jama.2023.5728 -
Intensive Care Medicine Mar 2022Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial.
PURPOSE
Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes.
METHODS
Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10.
RESULTS
Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI 7.5-9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5-1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5-6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7-7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9-6.9, p < 0.001).
CONCLUSION
TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question.
Topics: Adult; Anti-Bacterial Agents; Drug Monitoring; Female; Humans; Multiple Organ Failure; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis
PubMed: 35106617
DOI: 10.1007/s00134-021-06609-6 -
JAMA Feb 2018Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial.
IMPORTANCE
Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections.
OBJECTIVE
To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis.
DESIGN, SETTING, AND PARTICIPANTS
Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region.
INTERVENTIONS
Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment.
MAIN OUTCOMES AND MEASURES
Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated.
RESULTS
Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam.
CONCLUSIONS AND RELEVANCE
Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT02166476.
Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Boronic Acids; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Pyelonephritis; Thienamycins; Urinary Tract Infections; Urine
PubMed: 29486041
DOI: 10.1001/jama.2018.0438 -
The Journal of Antimicrobial... Feb 2023Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains...
BACKGROUND
Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown.
OBJECTIVE
Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI.
PATIENTS AND METHODS
We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI.
RESULTS
Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25).
CONCLUSIONS
We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.
Topics: Child; Young Adult; Humans; Piperacillin; Vancomycin; Retrospective Studies; Drug Therapy, Combination; Anti-Bacterial Agents; Piperacillin, Tazobactam Drug Combination; Tazobactam; Acute Kidney Injury; Penicillanic Acid
PubMed: 36545869
DOI: 10.1093/jac/dkac416 -
BMJ Case Reports Feb 2018Periocular necrotising fasciitis is a rare but sight-threatening condition, which relies on clinical judgement to detect in a timely manner. A 51-year-old woman...
Periocular necrotising fasciitis is a rare but sight-threatening condition, which relies on clinical judgement to detect in a timely manner. A 51-year-old woman presented to a rural hospital with rapid onset bilateral eye swelling, erythema and pain and was started on broad spectrum intravenous antibiotics. Upon admission, she became septic and required fluid resuscitation and transfer to a higher level of care. She received debridement and continued intravenous antibiotics, with step down to oral when clinically stable. Rapid recognition and treatment of her condition resulted in a positive outcome.
Topics: Administration, Intravenous; Anti-Bacterial Agents; Diagnosis, Differential; Eyelid Diseases; Eyelids; Fasciitis, Necrotizing; Female; Humans; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Streptococcal Infections; Streptococcus pyogenes; Vancomycin
PubMed: 29472418
DOI: 10.1136/bcr-2017-220962 -
Clinics in Perinatology Mar 2015To prevent the devastating consequences of infection, most infants admitted to the neonatal intensive care unit are exposed to antibiotics. However, dosing regimens are... (Review)
Review
To prevent the devastating consequences of infection, most infants admitted to the neonatal intensive care unit are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, pharmacokinetic modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, pharmacokinetic data and dosing regimens for infants are now available for ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam.
Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Clindamycin; Humans; Infant; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Meropenem; Metronidazole; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Practice Guidelines as Topic; Thienamycins
PubMed: 25678003
DOI: 10.1016/j.clp.2014.10.009 -
Clinical Pharmacokinetics Jun 2022Although dose optimization studies have been performed for piperacillin and tazobactam separately, a combined integral analysis is not yet reported. As piperacillin and... (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
Although dose optimization studies have been performed for piperacillin and tazobactam separately, a combined integral analysis is not yet reported. As piperacillin and tazobactam pharmacokinetics are likely to show correlation, a combined pharmacokinetic model should be preferred to account for this correlation when predicting the exposure. Therefore, the aim of this study was to describe the pharmacokinetics and evaluate different dosing regimens of piperacillin and tazobactam in critically ill patients using an integral population pharmacokinetic model in plasma and urine.
METHODS
In this observational study, a total of 39 adult intensive care unit patients receiving piperacillin-tazobactam as part of routine clinical care were included. Piperacillin and tazobactam concentrations in plasma and urine were measured and analyzed using non-linear mixed-effects modeling. Monte Carlo simulations were performed to predict the concentrations for different dosing strategies and different categories of renal function.
RESULTS
A combined two-compartment linear pharmacokinetic model for both piperacillin and tazobactam was developed, with an output compartment for the renally excreted fraction. The addition of 24-h urine creatinine clearance significantly improved the model fit. A dose of 12/1.5 g/24 h as a continuous infusion is sufficient to reach a tazobactam concentration above the target (2.89 mg/L) and a piperacillin concentration above the target of 100% f T (minimum inhibitory concentration [MIC] ≤ 16 mg/L). To reach a target of 100% f T with an MIC of 16 mg/L, piperacillin doses of up to 20 g/24 h are inadequate. Potential toxic piperacillin levels were reached in 19.6% and 47.8% of the population with a dose of 12 g/24 h and 20 g/24 h, respectively.
CONCLUSIONS
A regular dose of 12/1.5 g/24 h is sufficient in > 90% of the critically ill population to treat infections caused by Escherichia coli and Klebsiella pneumoniae with MICs ≤ 8 mg/L. In case of infections caused by Pseudomonas aeruginosa with an MIC of 16 mg/L, there is a fine line between therapeutic and toxic exposure. Dosing guided by renal function and therapeutic drug monitoring could enhance target attainment in such cases.
GOV IDENTIFIER
NCT03738683.
Topics: Adult; Anti-Bacterial Agents; Critical Illness; Humans; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Tazobactam
PubMed: 35377133
DOI: 10.1007/s40262-022-01113-6