penicillanic acid profile

Penicillanic acid is a key intermediate in the biosynthesis of penicillin antibiotics. It is a bicyclic β-lactam compound that is produced by certain fungi. Penicillanic acid is not itself an antibiotic, but it is the core structure from which many penicillin derivatives are synthesized. Its importance lies in its ability to inhibit bacterial cell wall synthesis, leading to bacterial cell death. The study of penicillanic acid has been instrumental in understanding the mechanism of penicillin action and in the development of new antibiotics. Researchers continue to study penicillanic acid to explore its potential for new drug development and to understand the intricate biosynthesis pathways of penicillin.'

Penicillanic Acid: A building block of penicillin, devoid of significant antibacterial activity. (From Merck Index, 11th ed) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

penicillanic acid : A penam that consists of 3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane bearing a carboxy group at position 2 and having (2S,5R)-configuration. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

ID Source	ID
PubMed CID	6891
CHEMBL ID	325758
CHEBI ID	37806
SCHEMBL ID	462651
MeSH ID	M0016125

Synonym
2,2-dimethylpenam-3alpha-carboxylic acid
87-53-6
(2s,5r)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
CHEBI:37806 ,
penicillanic acid
4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-, (2s-cis)-
einecs 201-750-3
(2s-cis)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid
CHEMBL325758
unii-pis09h0qix
pis09h0qix ,
(2s-cis)-3,3-dimethyl-7-oxo-4-thia-1- azabicyclo(3.2.0)heptane-2-carboxylic acid
4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3,3- dimethyl-7-oxo-, (2s-cis)-
4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-, (2s,5r)-
4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-
penicillanic acid [mi]
DTXSID90236038
RBKMMJSQKNKNEV-RITPCOANSA-N
SCHEMBL462651
penicillansaure
Q27117271
EN300-25626764

Excerpt	Reference	Relevance
" Adverse reactions to oral therapy were minimal."	( Efficacy and safety of sequential treatment with parenteral sulbactam/ampicillin and oral sultamicillin for skeletal infections in children. Aronoff, SC; Blumer, JL; Jacobs, MR; Kalamchi, A; Makley, JT; Scoles, PV, )	0.13
" Adverse reactions were infrequent with the exception of injection-site pain, which occurred mainly after intramuscular injection and was reduced in incidence by concurrent administration of lidocaine."	( Sulbactam plus ampicillin: interim review of efficacy and safety for therapeutic and prophylactic use. Greenhalgh, K; Knirsch, AK; Lees, L; Milson, JA, )	0.13
" Amdinocillin/penicillin proved to be a safe and effective alternative to gentamicin/penicillin; no adverse reactions were noted nor did the regimen adversely affect renal or hepatic function."	( Efficacy, pharmacology, and safety of amdinocillin in treatment of neonates. de Louvois, J; Mulhall, A, 1983)	0.27
" The incidence of adverse reactions was similar in both groups."	( Efficacy and safety of piperacillin/tazobactam in skin and soft tissue infections. File, TM; Tan, JS, 1994)	0.29
" TAZ/PIPC or TAZ caused adverse change in reproductive performance of the F0 generation only at doses that caused maternal toxicity."	( [Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam(1)--Fertility and general reproduction study in rats with intraperitoneal administration]. Christian, MS; Hoberman, AM; Lochry, EA; Sato, T, 1994)	0.29
" In all trials, piperacillin/tazobactam was found to be safe and well tolerated."	( Safety profile of piperacillin/tazobactam in phase I and III clinical studies. DeVries, VG; Kuye, O; Morrow, CA; Tally, FP; Teal, J, 1993)	0.29
" Nine patients (4%) had severe adverse events related to piperacillin/tazobactam and requiring discontinuation of therapy."	( Efficacy, safety and tolerance of parenteral piperacillin/tazobactam in the treatment of patients with lower respiratory tract infections. Ajana, F; Beuscart, C; Chidiac, C; Lecocq, P; Leroy, O; Mouton, Y; Senneville, E, 1993)	0.29
" Side-effects were mild; the commonest adverse events noted were mild elevations of liver enzymes."	( The efficacy and safety of piperacillin/tazobactam in the therapy of bacteraemia. Wise, R, 1993)	0.29
" The adverse event rate was non-significantly lower in the piperacillin/ tazobactam group compared to the co-amoxiclav/aminoglycoside group (2% vs."	( Efficacy, safety, and tolerance of piperacillin/tazobactam compared to co-amoxiclav plus an aminoglycoside in the treatment of severe pneumonia. Grossenbacher, M; Imhof, E; Speich, R; Vogt, M; Zimmerli, W, 1998)	0.3
" No serious adverse drug reaction was found during the treatment with piperacillin/tazobactam."	( [Multicentre clinical trial on efficacy and safety of domestic piperacillin/tazobactam for treatment of acute bacterial infections]. Liu, Y; Wang, R; Yu, B, 2001)	0.31
"Domestic piperacillin/tazobactam is effective and safe for the treatment of acute bacterial infections."	( [Multicentre clinical trial on efficacy and safety of domestic piperacillin/tazobactam for treatment of acute bacterial infections]. Liu, Y; Wang, R; Yu, B, 2001)	0.31
" No clinical adverse events considered related to the study drug were noted, in particular, no cases of phlebitis, rash or stool changes."	( Safety evaluation of piperacillin/tazobactam in very low birth weight infants. Apfalter, P; Berger, A; Kretzer, V; Pollak, A; Rohrmeister, K; Zaknun, D, 2004)	0.32
" Drug-related adverse events for both study drugs were comparable in frequency and type."	( An open-label, randomized study comparing efficacy and safety of intravenous piperacillin/tazobactam and ampicillin/sulbactam for infected diabetic foot ulcers. Boghossian, J; Caputo, W; Dana, A; Gray, S; Harkless, L; Pollak, R; Wu, D, 2005)	0.33
"Although both study drugs provide safe and effective empiric treatment for moderate-to-severe infected diabetic foot ulcers, piperacillin/tazobactam has the advantage of covering Pseudomonas aeruginosa (bacteriologic success rate of 85."	( An open-label, randomized study comparing efficacy and safety of intravenous piperacillin/tazobactam and ampicillin/sulbactam for infected diabetic foot ulcers. Boghossian, J; Caputo, W; Dana, A; Gray, S; Harkless, L; Pollak, R; Wu, D, 2005)	0.33
" There were no clinical, laboratory or cranial ultrasound adverse effects associated with P/T use."	( The use of piperacillin/tazobactam (in association with amikacin) in neonatal sepsis: efficacy and safety data. Flidel-Rimon, O; Friedman, S; Leibovitz, E; Shinwell, ES, 2006)	0.33
" The frequencies of drug-related adverse events, most commonly diarrhea and elevated serum alanine aminotransferase levels, were similar in both treatment groups."	( Efficacy and safety of ertapenem versus piperacillin-tazobactam for the treatment of intra-abdominal infections requiring surgical intervention. Asperger, W; Chan, CY; Dela Pena, AS; DiNubile, MJ; Giezek, H; Kafka, R; Köckerling, F; Raz, R; Shivaprakash, M; Vrijens, F; Warren, B, 2006)	0.33
" There were no statistical differences between the groups in serious drug-related clinical adverse events, drug-related clinical adverse experiences leading to study discontinuation, or mortality."	( Randomized, multicenter, double-blind study of efficacy, safety, and tolerability of intravenous ertapenem versus piperacillin/tazobactam in treatment of complicated intra-abdominal infections in hospitalized adults. Abramson, MA; Jensen, EH; Namias, N; Solomkin, JS; Tomassini, JE, 2007)	0.34
"6% of patients receiving doripenem and piperacillin/tazobactam, respectively, had a drug-related adverse event."	( Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open-label, multicenter study. Friedland, I; Kaniga, K; Ketter, N; Lee, M; Lobo, SM; Niederman, M; Prokocimer, P; Réa-Neto, A; Schroeder, E, 2008)	0.35
"Piperacillin/tazobactam therapy is effective and safe empirical antibacterial therapy in febrile neutropenic patients with hematological malignancies."	( [Clinical effects and safety of piperacillin/tazobactam in treating neutropenic febrile patients with malignant hematopathy]. Hu, LD; Huang, XJ; Jia, JS; Li, J; Lu, KY; Wang, C; Wu, DP, 2009)	0.35
" Ceftolozane-tazobactam was well tolerated and systemic adverse events were uncommon."	( Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses. Benziger, D; Friedland, I; Hershberger, E; Miller, B; Trinh, M, 2012)	0.38
" A causality assessment of the adverse reaction identified the antibiotic as the most probable cause of the observation."	( A case of severe toxicity during coadministration of vincristine and piperacillin: are drug transporters involved in vincristine hypersensitivity and drug-drug interactions? Andres, CR; Benz-de Bretagne, I; Gendrot, C; Jonville-Bera, AP; Jourdain, A; Le Guellec, C; Tarfaoui, N, 2012)	0.38
" A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30."	( Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study. Alder, J; Arvis, P; Dryden, M; Gyssens, IC; Kujath, P; Nathwani, D; Reimnitz, P; Schaper, NC, 2013)	0.39
" No significant difference of adverse effect was found between two groups."	( Effectiveness and safety of generic formulation of piperacillin/tazobactam (Astaz-P) for treatment of infected patients at Siriraj Hospital. Charoenpong, L; Thamlikitkul, V; Tongsai, S, 2013)	0.39
" The adverse event rates were similar in the groups (50."	( Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. Friedland, I; Hershberger, E; Lucasti, C; Miller, B; Solomkin, J; Steenbergen, J; Yankelev, S, 2014)	0.4
" The study results in Japanese patients with febrile neutropenia demonstrate that tazobactam/piperacillin treatment is efficacious and safe in adults."	( Efficacy and safety of tazobactam/piperacillin as an empirical treatment for the patients of adult and child with febrile neutropenia in Japan. Akiyama, N; Kanda, Y; Saito, M; Tamura, K, 2015)	0.42
"We conclude that cefepime monotherapy and piperacillin-tazobactam are equally efficacious and safe in treating patients with febrile neutropenia."	( A clinical evaluation of efficacy and safety of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia in a tertiary care centre of north India. Aamir, M; Abrol, P; Punia, H; Sharma, D, 2016)	0.43
"To relate simulated piperacillin exposure with adverse events (AEs) in infants using EHR data, we identified infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012."	( Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin-Tazobactam Safety in Infants. Clark, R; Cohen-Wolkowiez, M; Gonzalez, D; Hornik, CP; Kelly, MS; Ku, LC; Salerno, S; Smith, PB, 2017)	0.46
" The safety end-point was absence of any adverse effects (AE)."	( [Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis]. Cuellar-Pompa, L; Lede, R; Rosanova, MT, 2021)	0.62
" Rates of adverse events were similar among studies."	( [Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis]. Cuellar-Pompa, L; Lede, R; Rosanova, MT, 2021)	0.62
" Adverse events were similar to the comparators."	( [Efficacy and safety of empirical treatment with piperacillin/tazobactan as monotherapy in episodes of neutropenia and fever in children with cancer: systematic review and meta-analysis]. Cuellar-Pompa, L; Lede, R; Rosanova, MT, 2021)	0.62
" Rates of adverse events were similar between treatment groups (any: ceftolozane/tazobactam, 59."	( Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial. Ashouri, N; Bensaci, M; Bradley, JS; Bruno, CJ; De Anda, C; Huntington, JA; Johnson, MG; Lonchar, J; Popejoy, MW; Rhee, EG; Roilides, E; Su, FH, 2023)	0.91
" Ceftolozane/tazobactam is a safe and effective new treatment option for children with cUTI, especially due to antibacterial-resistant Gram-negative pathogens."	( Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial. Ashouri, N; Bensaci, M; Bradley, JS; Bruno, CJ; De Anda, C; Huntington, JA; Johnson, MG; Lonchar, J; Popejoy, MW; Rhee, EG; Roilides, E; Su, FH, 2023)	0.91
" Adverse events (AEs) occurred in 80."	( Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection. Bensaci, M; Bruno, CJ; De Anda, C; Dementieva, N; Huntington, JA; Jackson, CA; Johnson, MG; Lonchar, J; Newland, J; Popejoy, MW; Rhee, EG; Su, FH, 2023)	0.91
"In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs."	( Efficacy and safety of piperacillin-tazobactam compared with meropenem in treating complicated urinary tract infections including acute pyelonephritis due to extended-spectrum β-lactamase-producing Cao, SS; Cui, B; Cui, F; Cui, J; Fan, BY; Fan, TT; Guan, Y; Ji, B; Li, MY; Li, SR; Wang, JW; Wang, L; Yan, CY; Zhang, W, 2023)	0.91
"This observational study demonstrated that TAZ/CTLZ in combination with metronidazole has a favorable effect without major drug-related adverse events for intraabdominal infection in the hepato-biliary-pancreatic field in clinical practice although the efficacy of TAZ/CTLZ may decrease in compromised patients."	( Efficacy and safety of tazobactam/ceftolozane in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice. Ishizawa, T; Kimura, K; Kinoshita, M; Kubo, S; Nishio, K; Ohira, G; Okada, T; Shinkawa, H; Shirai, D; Tanaka, S; Tani, N; Tauchi, J, 2023)	0.91
"In vivo microdialysis was well tolerated in piglets and children, with no significant adverse events reported."	( Microdialysis as a safe and feasible method to study target-site piperacillin-tazobactam disposition in septic piglets and children. Colman, R; De Cock, PA; De Paepe, P; Devreese, M; Dhont, E; Hermans, E; Vande Walle, J; Verougstraete, N; Zeitlinger, M, 2023)	0.91
"Microdialysis is a safe and applicable method for the measurement of tissue drug concentrations in piglets and children."	( Microdialysis as a safe and feasible method to study target-site piperacillin-tazobactam disposition in septic piglets and children. Colman, R; De Cock, PA; De Paepe, P; Devreese, M; Dhont, E; Hermans, E; Vande Walle, J; Verougstraete, N; Zeitlinger, M, 2023)	0.91

Excerpt	Reference	Relevance
" Noncompartmental methods were used for pharmacokinetic analysis."	( Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease. Dutta, A; Faulkner, R; Greene, DS; Halstenson, CE; Haynes, J; Johnson, CA; Kelloway, JS; Shapiro, BE; Tonelli, A; Zimmerman, SW, 1992)	0.28
" On the basis of concentrations in plasma, the following pharmacokinetic parameter values were obtained (values are means +/- standard deviations): maximum concentration of drug in serum, tazobactam, 27."	( Pharmacokinetics and tissue penetration of tazobactam and piperacillin in patients undergoing colorectal surgery. Brismar, B; Kinzig, M; Nord, CE; Sörgel, F, 1992)	0.28
" Although the kinetics of sulbactam in postpartem women and in surgical patients were similar to the kinetics in young men, the half-life of sulbactam (like that of ampicillin) was altered in the elderly, during labor, in neonates, and in patients with renal impairment."	( Pharmacokinetics of sulbactam/ampicillin in humans: a review. Foulds, G, )	0.13
" Noncompartmental and compartmental calculations resulted in similar pharmacokinetic parameters."	( Single-dose pharmacokinetics of intravenous sulbactam in pediatric patients. Guenin, K; Schaad, UB; Straehl, P, )	0.13
" The basic pharmacokinetic characteristics of sulbactam after parenteral administration are similar to those of ampicillin."	( Sulbactam/ampicillin. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic use. Brogden, RN; Campoli-Richards, DM, 1987)	0.27
" The half-life of BL-P1654 (2."	( Human pharmacokinetics of BL-P1654 compared with ampicillin. Clarke, JT; Kirby, WM; Libke, RD; Luthy, RP; Ralph, ED, 1974)	0.25
" The purpose of this study was to determine the pharmacokinetic disposition of this antibiotic."	( Pharmacokinetics of mecillinam in health subjects. Barriere, SL; Conte, JE; Gambertoglio, JG; Lin, ET, 1980)	0.26
" Mean peak plasma concentrations were approximately 50 micrograms/ml, and the plasma half-life was approximately 53 min."	( Multiple-dose pharmacokinetics of amdinocillin in healthy volunteers. Barriere, SL; Conte, JE; Gambertoglio, JG; Lin, ET, 1982)	0.26
"Sulbactam, a new beta-lactamase inhibitor, has pharmacokinetic characteristics in humans similar to those of ampicillin and amoxicillin."	( Pharmacokinetics of sulbactam in humans. Foulds, G; Hayes, SL; Marshall, DC; McMahon, FG; O'Brien, MM; Stankewich, JP; Weidler, DJ, 1983)	0.27
" The pharmacokinetic disposition of amdinocillin and cephalothin was determined, when administered alone or in combination to healthy volunteers, as well as the penetration of amdinocillin into human cerebrospinal fluid."	( Amdinocillin pharmacokinetics. Simultaneous administration with cephalothin and cerebrospinal fluid penetration. Barriere, SL; Conte, JE; Gambertoglio, JG; Lin, ET, 1983)	0.27
"The pharmacokinetic parameters of amdinocillin and pivamdinocillin were studied in 12 normal volunteers."	( Pharmacokinetics of amdinocillin and pivamdinocillin in normal volunteers. Christenson, JG; Francke, EL; Neu, HC; Ortiz-Neu, C; Srinivasan, S, 1983)	0.27
"To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam."	( Piperacillin-tazobactam pharmacokinetics in patients with intraabdominal infections. Burm, JP; Gill, MA; Jhee, SS; Kern, JW; Yellin, AE, )	0.13
"The estimated noncompartmental pharmacokinetic parameters (mean +/- SD) for piperacillin and tazobactam, respectively, were as follows: maximum concentration in plasma 218."	( Piperacillin-tazobactam pharmacokinetics in patients with intraabdominal infections. Burm, JP; Gill, MA; Jhee, SS; Kern, JW; Yellin, AE, )	0.13
" Pharmacokinetic variables of both components after they have been given together have been studied in healthy volunteers and in patients."	( Pharmacokinetics and tissue penetration of piperacillin/tazobactam with particular reference to its potential in abdominal and soft tissue infections. Kinzig, M; Sörgel, F, 1994)	0.29
"Pharmacokinetic and pharmacodynamic considerations in in vitro susceptibility testing are described, and the integration of pharmacokinetic and pharmacodynamic concepts in dosage-regimen design is explored."	( Combination beta-lactam and beta-lactamase-inhibitor therapy: pharmacokinetic and pharmacodynamic considerations. Dudley, MN, 1995)	0.29
" The pharmacokinetic behavior of tazobactam was very similar to that observed for piperacillin, supporting the use of these two agents in a fixed-dose combination."	( Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children. Blumer, JL; Goldfarb, J; Lemon, E; Reed, MD; Yamashita, TS, 1994)	0.29
" The pharmacokinetic parameters of piperacillin and tazobactam were evaluated and were similar to previous reports."	( Pharmacokinetics of tazobactam M1 metabolite after administration of piperacillin/tazobactam in subjects with renal impairment. Bansal, S; Doepner, M; Halstenson, CE; Johnson, CA; Keane, WF; Onorato, JJ; Sia, L; Tantillo, K; Wong, MO; Zimmerman, SW, 1994)	0.29
"To evaluate the pharmacokinetic and clinical effects of the newly developed combination antibiotic tazobactam/piperacillin (TAZ/PIPC, YP-14) on various infections in pediatric field, a study group was organized, and a joint research by 17 institutions and their related hospitals was conducted."	( [Comprehensive evaluation of pharmacokinetic and clinical studies on tazobactam/piperacillin in pediatric field]. Fujii, R; Fujita, K; Fukushima, N; Inyaku, F; Ishikawa, A; Okuno, A; Saijo, M; Takimoto, M; Wagatsuma, S; Yoshikawa, M, 1995)	0.29
" In contrast, tazobactam administered with piperacillin achieved higher plasma concentrations and had a longer half-life than tazobactam administered alone."	( Pharmacokinetic characteristics of piperacillin/tazobactam. Kinzig, M; Sörgel, F, 1994)	0.29
"The pharmacokinetic properties of piperacillin/tazobactam are summarized."	( The chemistry, pharmacokinetics and tissue distribution of piperacillin/tazobactam. Kinzig, M; Sörgel, F, 1993)	0.29
"An in vitro pharmacokinetic model was used to study the pharmacodynamics of piperacillin-tazobactam and piperacillin-sulbactam against gram-negative bacilli producing plasmid-encoded beta-lactamases."	( Importance of beta-lactamase inhibitor pharmacokinetics in the pharmacodynamics of inhibitor-drug combinations: studies with piperacillin-tazobactam and piperacillin-sulbactam. Lister, PD; Prevan, AM; Sanders, CC, 1997)	0.3
" The fixed drug preparation appeared to have ideal pharmacokinetic properties if renal function was normal or slightly impaired, but no data are available for critically ill patients in anuric renal failure."	( Pharmacokinetics of piperacillin and tazobactam in critically ill patients with renal failure, treated with continuous veno-venous hemofiltration (CVVH). Mulder, PO; Stegeman, CA; Uges, DR; van der Werf, TS; Zijlstra, JG, 1997)	0.3
"A modified Emax model was used to describe the pharmacodynamic effect."	( Pharmacokinetic-pharmacodynamic modelling of the in vitro antiinfective effect of piperacillin-tazobactam combinations. Dalla Costa, T; Derendorf, H; Nolting, A; Rand, K, 1997)	0.3
" Pharmacodynamic activity of the combinations can be prolonged by sufficiently high inhibitor concentrations."	( Pharmacokinetic-pharmacodynamic modelling of the in vitro antiinfective effect of piperacillin-tazobactam combinations. Dalla Costa, T; Derendorf, H; Nolting, A; Rand, K, 1997)	0.3
" peak concentration (30 minutes after the end of an infusion) was 20."	( Influence of piperacillin-tazobactam on pharmacokinetics of gentamicin given once daily. Hitt, CM; Nicolau, DP; Nightingale, CH; Patel, KB; Zhu, Z, 1997)	0.3
"Mathematical modeling methods were used to study pharmacokinetic and pharmacodynamic interactions of the antimicrobial combinations piperacillin plus ciprofloxacin and piperacillin plus tazobactam."	( Pharmacodynamic interactions of ciprofloxacin, piperacillin, and piperacillin/tazobactam in healthy volunteers. Forrest, A; Nix, DE; Schentag, JJ; Strenkoski-Nix, LC, 1998)	0.3
" The objective of this article is to evaluate the pharmacokinetic properties of three commercially available beta-lactamase inhibitors."	( Pharmacokinetic properties of beta-lactamase inhibitors. de la Pena, A; Derendorf, H, 1999)	0.3
"Based on published articles in the literature, the pharmacokinetic properties of the beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam are reviewed and compared."	( Pharmacokinetic properties of beta-lactamase inhibitors. de la Pena, A; Derendorf, H, 1999)	0.3
"When choosing combinations of a beta-lactam antibiotic with a beta-lactamase inhibitor, it is important to make sure that the pharmacokinetic properties of drug and inhibitor are similar and remain similar under changing pathophysiological conditions."	( Pharmacokinetic properties of beta-lactamase inhibitors. de la Pena, A; Derendorf, H, 1999)	0.3
"A population pharmacokinetic (PK) analysis was conducted to determine if piperacillin and tazobactam exhibited linear or nonlinear PKs and if incremental changes in the daily dosage of piperacillin affected tazobactam PKs."	( Piperacillin and tazobactam exhibit linear pharmacokinetics after multiple standard clinical doses. Auclair, B; Ducharme, MP, 1999)	0.3
" Based on pharmacodynamic data, cefepime is an appropriate empiric choice for treatment of nosocomial infections."	( Comparison of five beta-lactam antibiotics against common nosocomial pathogens using the time above MIC at different creatinine clearances. Kays, MB, 1999)	0.3
" No systematic changes in pharmacokinetic parameters were observed."	( Evaluating possible pharmacokinetic interactions between tobramycin, piperacillin, and a combination of piperacillin and tazobactam in patients with various degrees of renal impairment. Amorusi, P; Dowell, JA; Korth-Bradley, J; Milisci, M; Tantillo, K; Tse, S, 2001)	0.31
" Pharmacodynamic principles suggest that a similar efficacy can be realized with extended dosing intervals when a larger dose (e."	( Comparative pharmacokinetic and pharmacodynamic profile of piperacillin/tazobactam 3.375G Q4H and 4.5G Q6H. Capitano, B; Kim, MK; Mattoes, HM; Nicolau, DP; Nightingale, CH; Quintiliani, R; Xuan, D, 2002)	0.31
"To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin-tazobactam against commonly encountered pathogens."	( Pharmacokinetic and pharmacodynamic evaluation of two dosing regimens for piperacillin-tazobactam. Capitano, B; Kim, MK; Mattoes, HM; Nicolau, DP; Nightingale, CH; Quintiliani, R; Xuan, D, 2002)	0.31
"Although statistically significant differences in the pharmacodynamic profile were noted for the regimens, both provide adequate T>MIC against commonly encountered pathogens considered susceptible to piperacillin-tazobactam."	( Pharmacokinetic and pharmacodynamic evaluation of two dosing regimens for piperacillin-tazobactam. Capitano, B; Kim, MK; Mattoes, HM; Nicolau, DP; Nightingale, CH; Quintiliani, R; Xuan, D, 2002)	0.31
" Maximizing the time above the minimum inhibitory concentration (MIC) for a pathogen is the best pharmacodynamic predictor of efficacy."	( Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam when administered by continuous infusion and intermittent dosing. Burgess, DS; Waldrep, T, 2002)	0.31
" Five clinical isolates each of P aeruginosa and K pneumoniae were used for pharmacodynamic analyses."	( Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam when administered by continuous infusion and intermittent dosing. Burgess, DS; Waldrep, T, 2002)	0.31
" Using a previously validated population pharmacokinetic equation, steady-state serum concentrations were estimated for 210 patients who received piperacillin/tazobactam via CI."	( Pharmacodynamic profiling of continuously infused piperacillin/tazobactam against Pseudomonas aeruginosa using Monte Carlo analysis. Kuti, JL; Nicolau, D; Nightingale, CH; Quintiliani, R, 2002)	0.31
"The pharmacokinetic profile of antibiotics at the site of antiinfective action is one of the most important determinants of drug response, since it correlates the antimicrobial effect."	( [Pharmacokinetics of antibiotics in inflamed and healthy lung tissue]. Maier, A; Smolle-Jüttner, FM; Tomaselli, F, 2003)	0.32
"The primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through population pharmacokinetic modeling and to characterize its pharmacodynamic profile."	( Pharmacodynamic profiling of piperacillin in the presence of tazobactam in patients through the use of population pharmacokinetic models and Monte Carlo simulation. Danziger, LH; Drusano, GL; Lodise, TP; Lomaestro, B; Rodvold, KA, 2004)	0.32
" According to pharmacokinetic modelling, the daily dose was reduced by 33% in patients receiving continuous infusion compared with intermittent infusion."	( Pharmacokinetics of piperacillin-tazobactam: intermittent dosing versus continuous infusion. Ackermann, T; Bertram, N; Buck, C; Derendorf, H; Paar, WD; Sauerbruch, T, 2005)	0.33
" NONMEM was used to perform population pharmacokinetic analysis in a subset of patients (n = 56) who had serum samples obtained at steady-state for drug concentration analyses."	( Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection. Dana, A; Kuti, JL; Li, C; Mansfield, DL; Nicolau, DP; Nightingale, CH, 2005)	0.33
" For patients (n = 30) receiving intermittent infusion in the pharmacokinetic study, mean Cmax and half-life were 122."	( Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection. Dana, A; Kuti, JL; Li, C; Mansfield, DL; Nicolau, DP; Nightingale, CH, 2005)	0.33
" Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N=39) and on pharmacokinetic data from peer-reviewed literature."	( Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms. Burgess, DS; Frei, CR; Reese, AM, 2005)	0.33
" Pharmacokinetic parameters, obtained from previously published studies in healthy volunteers were used to simulate the %T > MIC for 10,000 patients receiving imipenem-cilastatin, meropenem, and piperacillin/tazobactam."	( Pharmacodynamic modeling of beta-lactam antibiotics for the empiric treatment of secondary peritonitis: a report from the OPTAMA program. Kotapati, S; Kuti, JL; Nicolau, DP, 2005)	0.33
"To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease."	( Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program. Kuti, JL; Nicolau, DP; Sun, HK, 2005)	0.33
" The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated."	( Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program. Kuti, JL; Nicolau, DP; Sun, HK, 2005)	0.33
"The bactericidal exposures necessary for positive clinical outcomes among skin and soft tissue infections are largely dependent on interpatient pharmacokinetic variability and pathogen drug susceptibility."	( Pharmacodynamic modeling of imipenem-cilastatin, meropenem, and piperacillin-tazobactam for empiric therapy of skin and soft tissue infections: a report from the OPTAMA Program. Kuti, JL; Nicolau, DP; Ong, CT, 2005)	0.33
"An improved HPLC method was developed for the determination of piperacillin and tazobactam in human plasma and pharmacokinetic study in Chinese healthy volunteers."	( An improved high-performance liquid chromatographic method with a solid-phase extraction for the determination of piperacillin and tazobactam: application to pharmacokinetic study of different dosage in Chinese healthy volunteers. Wang, GJ; Xia, CH; Xiong, YQ, 2007)	0.34
"To report pharmacokinetic alterations and optimal dosing of piperacillin/tazobactam in an obese patient."	( Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. Adeyemi, OA; Montevecchi, M; Newman, D; Nicolau, DP; Noskin, GA; Postelnick, MJ; Scheetz, MH, 2007)	0.34
" Pharmacokinetic parameters such as maximal serum concentration, minimal serum concentration, average steady-state concentration, half-life, elimination rate constant, volume of distribution (V(d)), clearance, area under the curve at steadystate, and percent of time greater than the minimum inhibitory concentration (%t>MIC) were calculated and qualitatively compared between the sample and the population."	( Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. Adeyemi, OA; Montevecchi, M; Newman, D; Nicolau, DP; Noskin, GA; Postelnick, MJ; Scheetz, MH, 2007)	0.34
"A pharmacodynamic model was used to generate supportive data comparing tigecycline with other broad-spectrum agents against pathogens implicated in hospital-acquired pneumonia (HAP)."	( A pharmacodynamic simulation to assess tigecycline efficacy for hospital-acquired pneumonia compared with other common intravenous antibiotics. Dowzicky, M; Kuti, JL; Nicolau, DP, 2008)	0.35
"Computer modeling was used to integrate national in vitro microbiologic data from 2002 with pharmacokinetic data from published studies in healthy volunteers."	( Pharmacokinetic/pharmacodynamic modeling to predict in vivo effectiveness of various dosing regimens of piperacillin/tazobactam and piperacillin monotherapy against gram-negative pulmonary isolates from patients managed in intensive care units in 2002. Burgess, DS; Frei, CR, 2008)	0.35
"This randomized crossover study in healthy participants assessed pharmacokinetic interactions between telavancin, aztreonam, and piperacillin/tazobactam."	( Lack of pharmacokinetic drug interactions following concomitant administration of telavancin with aztreonam or piperacillin/tazobactam in healthy participants. Barriere, SL; Goldberg, MR; Kinzig, M; Kitt, MM; Sörgel, F; Wong, SL, 2009)	0.35
"5 g every 8 h (q8h), infused over 4 h, and pharmacokinetic parameters were determined by non-compartmental methods."	( Steady-state pharmacokinetics and pharmacodynamics of piperacillin/tazobactam administered by prolonged infusion in hospitalised patients. Cheatham, SC; Kays, MB; Shea, KM; Smith, DW; Sowinski, KM; Wack, MF, 2009)	0.35
"With increasing antibiotic resistance in gram-negative pathogens, dosing strategies that optimize pharmacodynamic parameters of currently available antibiotics play an important role in treatment."	( Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulation and steady-state pharmacokinetic data from hospitalized patients. Rotschafer, JC; Ullman, M, 2009)	0.35
"To compare the pharmacodynamics of several dosing regimens of piperacillin/tazobactam administered by intermittent and prolonged infusion using pharmacokinetic data from hospitalized patients."	( Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Cheatham, SC; Kays, MB; Shea, KM; Smith, DW; Sowinski, KM; Wack, MF, 2009)	0.35
" Alternative dosing regimens, which may include administration by extended or continuous infusion of piperacillin-tazobactam as a mechanism to increase the likelihood of pharmacodynamic target attainment, are described."	( Pharmacokinetic evaluation of piperacillin-tazobactam. Hayashi, Y; Lipman, J; Paterson, DL; Roberts, JA, 2010)	0.36
" This study measured the pharmacokinetic and pharmacodynamic characteristics of piperacillin-tazobactam in patients treated with continuous renal replacement therapy using contemporary equipment and prescriptions."	( Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Bauer, SR; Connor, MJ; Fissell, WH; Groszek, J; Salem, C; Taylor, ME; Tolwani, AJ; Wei, P, 2012)	0.38
" Pharmacokinetic and pharmacodynamic parameters were calculated using standard equations."	( Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Bauer, SR; Connor, MJ; Fissell, WH; Groszek, J; Salem, C; Taylor, ME; Tolwani, AJ; Wei, P, 2012)	0.38
"052 h(-1)) were highly variable, and clinical parameters could explain only a small fraction of the large variability in pharmacokinetic parameters."	( Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Bauer, SR; Connor, MJ; Fissell, WH; Groszek, J; Salem, C; Taylor, ME; Tolwani, AJ; Wei, P, 2012)	0.38
" Many patients did not achieve pharmacodynamic targets, suggesting that therapeutic drug monitoring might optimize therapy."	( Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Bauer, SR; Connor, MJ; Fissell, WH; Groszek, J; Salem, C; Taylor, ME; Tolwani, AJ; Wei, P, 2012)	0.38
" After a single dose of ceftolozane alone, the ranges of mean values for half-life (2."	( Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses. Benziger, D; Friedland, I; Hershberger, E; Miller, B; Trinh, M, 2012)	0.38
"Prospective, observational, multicenter, pharmacokinetic study."	( Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study. Bellomo, R; Cole, L; Lipman, J; Liu, X; Nair, P; Roberts, DM; Roberts, JA; Roberts, MS, 2012)	0.38
"While extended infusions of piperacillin-tazobactam (TZP) are increasingly used in practice, the effect of infusion on the pharmacokinetic (PK) profile of TZP has not been widely assessed."	( Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections. Butterfield, JM; Drusano, GL; Felton, TW; Hope, WW; Kwa, AL; Lodise, TP; Lomaestro, BM, 2012)	0.38
" Pharmacokinetic parameters were estimated and 5000-patient Monte Carlo simulations were performed for four prolonged-infusion dosing regimens."	( Steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients. Cheatham, SC; Chung, CE; Fleming, MR; Healy, DP; Humphrey, ML; Kays, MB; Shea, KM, 2013)	0.39
"To develop population pharmacokinetic (PK) models for piperacillin/tazobactam in neonates and infants of less than 2 months of age in order to determine the appropriate dosing regimen and provide a rational basis for the development of preliminary dosing guidelines suitable for this population."	( Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants. Cao, D; Cao, Y; Chen, C; Chen, Y; Li, Q; Li, Z; Shi, W; Wang, Y; Wu, D; Zhu, Y, 2013)	0.39
"56 mg/kg/dose piperacillin/tazobactam every 8 or 12 h evaluated in this study achieved the pharmacodynamic target (free piperacillin concentrations >4 mg/L for more than 50 % of the dosing interval) in about 67 % of infants."	( Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants. Cao, D; Cao, Y; Chen, C; Chen, Y; Li, Q; Li, Z; Shi, W; Wang, Y; Wu, D; Zhu, Y, 2013)	0.39
"This was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center."	( Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Carlier, M; Carrette, S; De Waele, JJ; Decruyenaere, J; Depuydt, P; Hoste, E; Lipman, J; Roberts, JA; Stove, V; Verstraete, A; Wallis, SC, 2013)	0.39
"We obtained data from 61 patients and observed extensive pharmacokinetic variability."	( Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Carlier, M; Carrette, S; De Waele, JJ; Decruyenaere, J; Depuydt, P; Hoste, E; Lipman, J; Roberts, JA; Stove, V; Verstraete, A; Wallis, SC, 2013)	0.39
"To evaluate the steady-state pharmacokinetic and pharmacodynamic parameters of piperacillin in morbidly obese, surgical intensive care patients."	( Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Allen, N; Fish, DN; Newell, M; Rafferty, KD; Sturm, AW; Toschlog, E; Waibel, B, 2014)	0.4
" Serum piperacillin concentrations were determined by using a validated high-performance liquid chromatography assay; these concentrations were used to estimate pharmacokinetic parameters, and 5000-patient Monte Carlo simulations were performed."	( Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Allen, N; Fish, DN; Newell, M; Rafferty, KD; Sturm, AW; Toschlog, E; Waibel, B, 2014)	0.4
" Population pharmacokinetic models were fitted to the data utilizing first-order, Michaelis-Menten (MM) and parallel first-order/MM clearance."	( Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations. Beegle, S; Butterfield, JM; Farkas, J; Lodise, TP; Pai, MP; Rosen, J, 2014)	0.4
"Piperacillin/tazobactam is a frequently prescribed antibiotic in pediatric intensive care units, but pharmacokinetic data to justify the optimal piperacillin/tazobactam dosing regimen are sparse in critically ill children."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill young children. Cies, JJ; Kuti, JL; Schlichting, C; Shankar, V, 2014)	0.4
"These are the first pharmacokinetic data of piperacillin/tazobactam (piperacillin component) in critically ill pediatric patients (1-6 years of age)."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill young children. Cies, JJ; Kuti, JL; Schlichting, C; Shankar, V, 2014)	0.4
"Population pharmacokinetic models have been developed and validated for piperacillin and tazobactam."	( Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis. Asín-Prieto, E; Isla, A; Maynar, J; Rodríguez-Gascón, A; Sánchez-Izquierdo, JÁ; Soraluce, A; Trocóniz, IF, 2014)	0.4
" The following pharmacokinetic measurements were obtained: maximum concentration, 94."	( Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy. Álvarez, JC; Cortés, JA; Cuervo, SI; Díaz, JA; Garzón, JR; Gómez, JC; Sánchez, R; Silva, E, 2013)	0.39
"Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1(/2) and decreased CL."	( Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy. Álvarez, JC; Cortés, JA; Cuervo, SI; Díaz, JA; Garzón, JR; Gómez, JC; Sánchez, R; Silva, E, 2013)	0.39
"This prospective pharmacokinetic study aimed to describe plasma and interstitial fluid (ISF) pharmacokinetics of piperacillin and tazobactam in critically ill patients on continuous venovenous haemodiafiltration (CVVHDF)."	( Pharmacokinetics of piperacillin and tazobactam in plasma and subcutaneous interstitial fluid in critically ill patients receiving continuous venovenous haemodiafiltration. Boots, RJ; Jarrett, P; Kirkpatrick, CM; Lipman, J; Roberts, JA; Varghese, JM, 2014)	0.4
"Since antimicrobial resistance among uropathogens against current first line agents has affected the management of severe urinary tract infection, we determined the likelihood that antibiotic regimens achieve bactericidal pharmacodynamic exposures using Monte Carlo simulation for five antimicrobials (ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ertapenem, and meropenem) commonly prescribed as initial empirical treatment of inpatients with severe community acquired urinary tract infections."	( Pharmacodynamic profiling of commonly prescribed antimicrobial drugs against Escherichia coli isolates from urinary tract. Cuba, GT; Kiffer, CR; Luchesi, LJ; Patekoski, KS; Pignatari, AC, )	0.13
" The purpose of this study was to develop a population pharmacokinetic (PK) model for piperacillin in burn patients and to predict the probability of target attainment (PTA) using MICs and concentrations simulated from the PK model."	( Population pharmacokinetic analysis of piperacillin in burn patients. Han, S; Hong, T; Jeon, S; Lee, J; Paek, J; Woo, H; Yim, DS, 2014)	0.4
" We used pharmacokinetic data to evaluate the diagnostic accuracy of a recently proposed ARC score."	( Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. Akers, KS; Cannon, JW; Chung, KK; Cota, JM; Murray, CK; Niece, KL, 2014)	0.4
" We combined intermediate scores (4-6 points) into a single low score (≤6) group and compared pharmacokinetic parameters against the high (≥7) ARC score group."	( Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. Akers, KS; Cannon, JW; Chung, KK; Cota, JM; Murray, CK; Niece, KL, 2014)	0.4
" Monte Carlo pharmacokinetic simulations demonstrated increased time at therapeutic drug levels with extended infusion dosing at a drug cost savings of up to 66."	( Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. Akers, KS; Cannon, JW; Chung, KK; Cota, JM; Murray, CK; Niece, KL, 2014)	0.4
" Serum concentration data from 376 adults who received ceftolozane/tazobactam in doses ranging from 500 to 3000 mg were analyzed to identify factors contributing to the pharmacokinetic variability."	( Population pharmacokinetics of ceftolozane/tazobactam in healthy volunteers, subjects with varying degrees of renal function and patients with bacterial infections. Chandorkar, G; Hershberger, E; Krishna, G; Mouksassi, MS; Xiao, A, 2015)	0.42
"This pharmacokinetic study included 21 pediatric (age 3-10 years) patients receiving piperacillin/tazobactam to treat fever with neutropenia."	( Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia. Cies, JJ; Jain, J; Kuti, JL, 2015)	0.42
"In children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure."	( Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia. Cies, JJ; Jain, J; Kuti, JL, 2015)	0.42
" Drug exposure was expressed as the ratio of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (fAUC/MIC) (VAN) or the time in a 24-h period that the drug concentration for the free, unbound fraction exceeded the MIC under steady-state pharmacokinetic conditions (fT(>MIC)) (SAM and TZP) and linked to the change in log10 CFU/thigh."	( An optimized mouse thigh infection model for enterococci and its impact on antimicrobial pharmacodynamics. Agudelo, M; Gonzalez, JM; Rodriguez, CA; Vesga, O; Zuluaga, AF, 2015)	0.42
" There were no significant differences in serum concentrations or pharmacokinetic parameters between ECMO and non-ECMO patients, including Vd [0."	( β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study. Antonucci, E; Beumier, M; Cristallini, S; de Backer, D; Donadello, K; Jacobs, F; Roberts, JA; Rondelet, B; Scolletta, S; Taccone, FS; Vincent, JL, 2015)	0.42
" The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD)."	( [Experimental study on concentrations and pharmacokinetics of antibiotics in bile and evaluation of their microbicidal potential]. Lai, J; Li, S; Liang, L; Peng, B; Wang, Z; Zheng, J, 2014)	0.4
" Population pharmacokinetic parameters were estimated using NONMEM, and Monte Carlo simulations were performed for three 4-hour dosing regimens to calculate probability of target attainment (PTA) at ≥50% fT>MIC."	( Population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients. Cheatham, SC; Chung, EK; Fleming, MR; Healy, DP; Kays, MB; Shea, KM, 2015)	0.42
" Surprisingly, although tazobactam has been available for over 20 years, few if any reliable data exist on the tazobactam pharmacokinetic (PK) properties in mice."	( Plasma and epithelial lining fluid pharmacokinetics of ceftolozane and tazobactam alone and in combination in mice. Lagarde, C; Mavridou, E; Melchers, MJ; Mouton, JW; Seyedmousavi, S; van Mil, AC, 2015)	0.42
"The study was to establish a population pharmacokinetic (PPK) model of piperacillin (PIP) and tazobactam (TAZ) that explain pharmacokinetic variability and to propose optimized dosage regimens in patients with nosocomial infections."	( Population Pharmacokinetics and Pharmacodynamics of Piperacillin/Tazobactam in Patients with Nosocomial Infections. Chen, R; Qian, CY; Qian, Q; Sun, MR; Wang, LY; Wang, ML; Zou, SL, 2016)	0.43
"To evaluate the pharmacokinetic and pharmacodynamic profiles of piperacillin-tazobactam administered as a 4-hour infusion in critically ill patients undergoing continuous renal replacement therapy (CRRT)."	( Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy. Amyot, J; Awissi, DK; Beauchamp, A; Fagnan, M; Hébert, E; Lavallée, C; Lavigne, V; Leblanc, M; Lebrun, G; Munoz, DL; Pichette, V; Robitaille, R; Savoie, M; Tétreault, N; Varin, F, 2015)	0.42
"Prospective, observational, pharmacokinetic study."	( Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy. Amyot, J; Awissi, DK; Beauchamp, A; Fagnan, M; Hébert, E; Lavallée, C; Lavigne, V; Leblanc, M; Lebrun, G; Munoz, DL; Pichette, V; Robitaille, R; Savoie, M; Tétreault, N; Varin, F, 2015)	0.42
" Regarding piperacillin pharmacokinetic parameters, the median (interquartile range) minimum unbound plasma concentration was 65."	( Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy. Amyot, J; Awissi, DK; Beauchamp, A; Fagnan, M; Hébert, E; Lavallée, C; Lavigne, V; Leblanc, M; Lebrun, G; Munoz, DL; Pichette, V; Robitaille, R; Savoie, M; Tétreault, N; Varin, F, 2015)	0.42
"Administration of a 4-hour infusion of piperacillin-tazobactam was associated with a favorable pharmacodynamic profile in patients undergoing CRRT."	( Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy. Amyot, J; Awissi, DK; Beauchamp, A; Fagnan, M; Hébert, E; Lavallée, C; Lavigne, V; Leblanc, M; Lebrun, G; Munoz, DL; Pichette, V; Robitaille, R; Savoie, M; Tétreault, N; Varin, F, 2015)	0.42
" A population pharmacokinetic (PK) model with the plasma-to-epithelial lining fluid (ELF) kinetics of ceftolozane/tazobactam was used to justify dosing regimens for patients with nosocomial pneumonia in phase 3 studies."	( Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. Huntington, JA; Miller, BW; Nicolau, DP; Xiao, AJ, 2016)	0.43
"Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population."	( Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations? Brock, B; Gjedsted, J; Hardlei, TF; Juul, RV; Kreilgaard, M; Öbrink-Hansen, K; Storgaard, M; Thomsen, MK, 2015)	0.42
"This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries."	( Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DA Abdul-Aziz, MH; Akova, M; Bassetti, M; De Waele, JJ; Dimopoulos, G; Dulhunty, J; Kaukonen, KM; Koulenti, D; Lipman, J; Martin, C; Montravers, P; Rello, J; Rhodes, A; Roberts, JA; Starr, T; Wallis, SC, 2016)	0.43
" In this study, we studied the pharmacodynamics of ceftolozane plus tazobactam against Escherichia coli and Pseudomonas aeruginosa using an in vitro pharmacokinetic model of infection."	( Pharmacodynamics of Ceftolozane plus Tazobactam Studied in an In Vitro Pharmacokinetic Model of Infection. Bowker, KE; MacGowan, AP; Nicholls, D; Noel, AR; Tomaselli, SG, 2016)	0.43
" PK variables: total and renal clearance (CLtot, CLR), volume of distribution (Vd), and elimination half-life (T1/2) were calculated, followed by glomerular filtration rate (MDRD) and cumulative fluid balance (CFB-total fluid volume based on 24-h registered fluid intake minus output)."	( A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam. Bezouška, J; Havel, E; Kaška, M; Malbrain, ML; Martínková, J; Šafránek, P, 2016)	0.43
"63 μg/ml, time to Cmax (Tmax) of 4 h, area under the concentration-time curve from 0 to 8 h (AUC0-8) of 284."	( Ceftolozane-Tazobactam Pharmacokinetics in a Critically Ill Patient on Continuous Venovenous Hemofiltration. Gonzales, JP; Heil, EL; Mehrotra, S; Nicolau, DP; Oliver, WD; Robinett, K; Saleeb, P, 2015)	0.42
"9 m(2) AN69 membranes); and (ii) for the treatment of bacteria with high susceptibility to piperacillin (MIC <4 mg/L) or for the attainment of a more traditional pharmacodynamic target (50%fuT>MIC), 2000 mg q8h sufficed regardless of type of membrane and body weight."	( Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: effect of type of dialysis membrane on dosing requirements. Calvo, G; Fernández, J; Llauradó-Serra, M; Martín-Loeches, I; Pontes, C; Rodríguez, A; Soy, D; Torres, A; Ulldemolins, M; Vaquer, S, 2016)	0.43
" Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression."	( Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT. Aduroja, OA; Amde, M; Connor, MJ; Fissell, WH; Gould, ER; Groszek, JJ; Madonia, PN; Nesbitt, R; Salem, C; Shotwell, MS; Taylor, ME; Tolwani, AJ; Wei, P, 2016)	0.43
"Population pharmacokinetic (popPK) analyses for piperacillin/tazobactam in neonates and infants of less than 2 months of age have been performed by our group previously."	( Target attainment analysis and optimal sampling designs for population pharmacokinetic study on piperacillin/tazobactam in neonates and young infants. Chen, C; Chen, Y; Dong, M; Li, Q; Li, Z; Lu, J; Wu, D; Zhu, Y, 2016)	0.43
" Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT."	( Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy. Chaijamorn, W; Lewis, SJ; Mueller, BA; Shaw, AR, 2017)	0.46
" MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates."	( Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy. Chaijamorn, W; Lewis, SJ; Mueller, BA; Shaw, AR, 2017)	0.46
" Using a previously published population pharmacokinetic model in the target population, we simulated piperacillin steady state area under the concentration versus time curve from zero to τ (AUCss,0-τ) and steady state maximal drug concentration (Cmaxss)."	( Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin-Tazobactam Safety in Infants. Clark, R; Cohen-Wolkowiez, M; Gonzalez, D; Hornik, CP; Kelly, MS; Ku, LC; Salerno, S; Smith, PB, 2017)	0.46
"This prospective pharmacokinetic study aimed to compare the clearance of piperacillin-tazobactam administered as a 24-h continuous infusion between continuous venovenous haemodiafiltration (CVVHDF) and continuous venovenous haemofiltration (CVVH) applied at equal dose in critically ill patients."	( Impact of renal replacement modalities on the clearance of piperacillin-tazobactam administered via continuous infusion in critically ill patients. Cotta, MO; Lefrant, JY; Lipman, J; Muller, L; Roberts, JA; Roger, C; Wallis, SC, 2017)	0.46
" A pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug concentrations was conducted to simulate dosing regimens needed to attain the pharmacodynamic target in abdominal sites."	( Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and peritoneum of surgery patients, and dosing considerations based on site-specific pharmacodynamic target attainment. Ikawa, K; Kajihara, T; Morikawa, N; Murakami, Y; Murao, N; Ohge, H; Shigemoto, N; Shimada, N; Sueda, T; Uegami, S; Uemura, K; Watadani, Y; Yano, R, 2017)	0.46
" Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates."	( Dosing antibiotics in neonates: review of the pharmacokinetic data. Cohen-Wolkowiez, M; Greenberg, RG; Rivera-Chaparro, ND, 2017)	0.46
" This review summarizes the population pharmacokinetic models developed for piperacillin-tazobactam and provides comprehensive data on current dosing strategies while identifying significant covariates in critically ill patients."	( Piperacillin-Tazobactam in Intensive Care Units: A Review of Population Pharmacokinetic Analyses. Caissy, JA; El-Haffaf, I; Marsot, A, 2021)	0.62
" Steady state free ceftolozane plasma Cmax and Cmin concentrations were calculated to be 122."	( Ceftolozane/tazobactam for refractory P. aeruginosa endocarditis: A case report and pharmacokinetic analysis. Bremmer, DN; Kline, EG; Nicolau, DP; Shah, S; Shields, RK, 2022)	0.72
" We sought to aggregate previously published piperacillin and tazobactam (pip-tazo) pharmacokinetic data in critically ill patients undergoing CKRT to better understand pharmacokinetics of pip-tazo in this population and better inform dosing."	( Pharmacokinetics of piperacillin and tazobactam in critically Ill patients treated with continuous kidney replacement therapy: A mini-review and population pharmacokinetic analysis. Akers, KS; Chung, KK; DeLuca, JP; Livezey, JR; Nadeau, RJ; Por, ED; Pruskowski, KA; Selig, DJ, 2022)	0.72
" Of the 26 articles, 10 for piperacillin and 8 for tazobactam had complete information suitable for population pharmacokinetic modelling."	( Pharmacokinetics of piperacillin and tazobactam in critically Ill patients treated with continuous kidney replacement therapy: A mini-review and population pharmacokinetic analysis. Akers, KS; Chung, KK; DeLuca, JP; Livezey, JR; Nadeau, RJ; Por, ED; Pruskowski, KA; Selig, DJ, 2022)	0.72
" The proportion of patients meeting pre-defined pharmacodynamic (PD) targets (median 88."	( Pharmacokinetics of piperacillin and tazobactam in critically Ill patients treated with continuous kidney replacement therapy: A mini-review and population pharmacokinetic analysis. Akers, KS; Chung, KK; DeLuca, JP; Livezey, JR; Nadeau, RJ; Por, ED; Pruskowski, KA; Selig, DJ, 2022)	0.72
"Similar ratios of generic/originator (90% CI) Cmax were observed for Cefepime-MIP/Maxipime [93."	( Comparison of pharmacokinetics and stability of generics of cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs: an intravenous bioequivalence study in healthy volunteers. Al Jalali, V; Ballarini, N; Bauer, M; Bergmann, F; Jorda, A; König, F; Lackner, E; Nussbaumer-Pröll, A; Oesterreicher, Z; Reiter, B; Stimpfl, T; Wölfl-Duchek, M; Wulkersdorfer, B; Zeitlinger, M, 2022)	0.72
" The population pharmacokinetic models that best characterized the observed plasma concentrations of piperacillin and tazobactam were one-compartment structural models with zero-order input and linear elimination."	( Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan. An, G; Balevic, SJ; Chan, AW; Cohen-Wolkowiez, M; Conrad, T; Gu, K; Hemmersbach-Miller, M; Kirkpatrick, CMJ; Landersdorfer, CB; Schmader, KE; Swamy, GK; Walter, EB; Winokur, PL, 2023)	0.91

Excerpt	Reference	Relevance
" The combination of ampicillin or cefazolin with mecillinam leads to bactericidal acceleration; the effects are comparable to those of the combination with gentamycin."	( [Effects of ampicillin and cefazolin combined with mecillinam (author's transl)]. Bischof-Léger, E; Helm, EB; Stille, W, 1978)	0.26
"The minimal inhibitory concentrations of piperacillin (PIP) or cefotaxime (CTX) alone or in combination with tazobactam (TAZ) were determined against 168 anaerobes."	( [Strict anaerobic bacteria: comparative study of various beta-lactam antibiotics in combination with tazobactam or sulbactam]. Dubreuil, L; Sedallian, A, 1991)	0.28
" The absence of the outer membrane proteins, OmpF and OmpC, did not significantly affect susceptibility to the combinations per se but when combined with the presence of beta-lactamase high MICs were observed."	( Factors determining resistance to beta-lactam combined with beta-lactamase inhibitors in Escherichia coli. Baquero, F; Martínez, JL; Pérez-Díaz, JC; Reguera, JA, 1991)	0.28
"Tazobactam (YTR 830), a new beta-lactamase inhibitor, was evaluated for its effect in combination with piperacillin, a broad spectrum, but beta-lactamase sensitive, penicillin, against 14 common bacteria."	( Antimicrobial activities of piperacillin alone and in combination with tazobactam against beta-lactamase-producing bacteria. Chang, SC; Hsieh, WC; Hsu, LY; Luh, KT, 1991)	0.28
"The in-vitro synergistic activity of tazobactam, a new beta-lactamase inhibitor, combined with piperacillin was tested against various beta-lactamase-producing strains."	( Inhibition of beta-lactamases by tazobactam and in-vitro antibacterial activity of tazobactam combined with piperacillin. Higashitani, F; Hyodo, A; Inoue, M; Ishida, N; Mitsuhashi, S, 1990)	0.28
"Cefpirome, a so-called fourth-generation cephalosporin, was tested alone and in combination with the sulfone beta-lactamase inhibitor, tazobactam, against 63 members of the Bacteroides fragilis group."	( Antimicrobial spectrum of cefpirome combined with tazobactam against the Bacteroides fragilis group. Barrett, MS; Croco, JL; Erwin, ME; Jones, RN; Novick, WJ, )	0.13
"We studied the efficacy of tazobactam (YTR 830), a new beta-lactamase inhibitor in combination with piperacillin (P) against 198 Enterobacteriaceae strains."	( [Efficiency of tazobactam as inhibitor of beta-lactamases, combined with piperacillin, against resistant strains to this penicillin]. Ràfols, M; Reig, R; Roy, C; Teruel, D; Tirado, M, 1989)	0.28
"YTR 830, a new beta-lactamase inhibitor, combined with amoxicillin or carbenicillin, showed a synergistic effect similar to that observed with clavulanic acid, and generally better than that with sulbactam, against strains harboring chromosome-encoded penicillinases and broad-spectrum beta-lactamases or plasmid-determined beta-lactamases."	( Comparative evaluation of a new beta-lactamase inhibitor, YTR 830, combined with different beta-lactam antibiotics against bacteria harboring known beta-lactamases. Acar, JF; Gutmann, L; Kitzis, MD; Yamabe, S, 1986)	0.27
"The in vitro synergistic activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam, combined with ampicillin, ticarcillin, mezlocillin, azlocillin, piperacillin, and apalcillin, were determined against 34 strains of members of the Enterobacteriaceae family, Pseudomonas aeruginosa, Aeromonas hydrophila, and Haemophilus influenzae with characterized plasmid or chromosomal beta-lactamases or both."	( Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with ampicillin and broad-spectrum penicillins against defined beta-lactamase-producing aerobic gram-negative bacilli. Aronoff, SC; Jacobs, MR; Johenning, S; Shlaes, DM; Yamabe, S, 1986)	0.27
"The in-vitro synergistic activity of YTR 830, a new beta-lactamase inhibitor, combined with four extended-spectrum penicillins (ticarcillin, piperacillin, mezlocillin and apalcillin) against ticarcillin-resistant clinical isolates of Gram-negative enteric bacilli was compared with that of clavulanate and sulbactam."	( Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads. Aronoff, SC; Jacobs, MR; Johenning, S; Yamabe, S, 1986)	0.27
"The in vitro activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with six beta-lactams against 88 beta-lactamase-producing anaerobes were determined."	( Comparative activity of beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with beta-lactams against beta-lactamase-producing anaerobes. Appelbaum, PC; Jacobs, MR; Spangler, SK; Yamabe, S, 1986)	0.27
"The in-vitro activity of a beta-lactamase inhibitor (clavulanic acid, sulbactam, BL-P2013 or BL-P2090) in combination with ampicillin against 13 isolates of Mycobacterium tuberculosis was determined by broth dilution."	( Comparison of four beta-lactamase inhibitors in combination with ampicillin against Mycobacterium tuberculosis. Cynamon, MH; Sorg, TB, 1987)	0.27
"The antibacterial activity of ampicillin against Enterobacteriaceae strongly increased when combined with 6 beta-bromopenicillanic acid (BPA) or clavulanic acid (CA)."	( In vitro activity of ampicillin alone and in combination with different concentrations of 6 beta-bromopenicillanic acid, clavulanic acid and mecillinam. Houben, AW; Stobberingh, EE; van Boven, CP, 1987)	0.7
"Several in vitro parameters of sulbactam combined with ampicillin (Sbt/Amp) were studied in order to evaluate and compare its microbiological properties with those of beta-lactamase stable beta-lactams (ceftriaxone, cefamandole, cefoxitin)."	( Microbiological properties of sulbactam combined with ampicillin. Barba, D; Esposito, S; Galante, D; Ruffilli, MP, 1987)	0.27
" Combined with amoxicillin, YTR 830 is a potentially useful agent for therapy of many bacterial infections."	( Comparative activities of the beta-lactamase inhibitors YTR 830, sodium clavulanate, and sulbactam combined with amoxicillin or ampicillin. Aronoff, SC; Jacobs, MR; Johenning, S; Yamabe, S, 1984)	0.27
"The results of three separate studies aimed at evaluating the efficacy of long-term, low-dose treatment with pivmecillinam alone, and in combination with pivampicillin, in patients prone to recurrent bacteriuria, are presented."	( Long-term, low-dose treatment with pivmecillinam alone and in combination with pivampicillin in patients prone to recurrent bacteriuria. Barclay, RP; Mejlhede, A; Nilsson, LB, 1982)	0.26
"The beta-lactamase inhibitors clavulanic acid and sulbactam were combined with mecillinam."	( Synergistic activity of mecillinam in combination with the beta-lactamase inhibitors clavulanic acid and sulbactam. Neu, HC, 1982)	0.26
"3 patients with salmonella infections who continued to excrete salmonella in fecal samples for more than 6 months were treated with pivmecillinam alone or in combination with pivampicillin."	( Treatment of Salmonella carriers with pivmecillinam alone or in combination with pivampicillin: experience with three patients. Bruun, JN; Bøe, J; Digranes, A; Maeland, A, 1983)	0.27
" Although amdinocillin, alone or in combination with cefoxitin, appeared effective as second-line therapy in infections with organisms shown sensitive in vitro, the combination of amdinocillin and ticarcillin or carbenicillin was only moderately effective in initial therapy for neutropenic, febrile, cancer patients."	( Amdinocillin: use alone or in combination with cefoxitin or carbenicillin-ticarcillin. Bodey, GP; Estey, EH; Lawson, RD, 1983)	0.27
"Scanning electron microscopy was used to study the morphologic effects of amdinocillin (mecillinam) when combined with several beta-lactam antibiotics in vitro (Escherichia coli, three isolates; Klebsiella pneumoniae, one isolate) and also in vivo (E."	( Morphologic changes produced by amdinocillin alone and in combination with beta-lactam antibiotics: in vitro and in vivo. Cleeland, R; Kramer, MJ; Mauriz, YR; Robertson, TL; Timmes, MD, 1983)	0.27
" We report the results of a multicenter study evaluating the safety and efficacy of amdinocillin in combination with other beta-lactam antibiotics in the treatment of 120 serious gram-negative bacterial infections."	( Systemic infections treated with amdinocillin in combination with other beta-lactam antibiotics. Beam, TR; King, JW; Neu, HC; Smith, LG, 1983)	0.27
"Amdinocillin in combination with another beta-lactam antibiotic (ampicillin, cephalothin, cefamandole or cefoxitin) was used to treat 25 patients with pyelonephritis (with or without bacteremia), pneumonia, bacteremia secondary to intravenous devices, and urinary tract infections (with catheter in place) due to gram-negative organisms."	( Amdinocillin in combination with beta-lactam antibiotics for treatment of serious gram-negative infections. Farrar, WE; Rotstein, C, 1983)	0.27
"The in-vitro activity of cefsulodin combined with sulbactam, cefoxitin or cefotaxime was investigated against 32 strains of beta-lactamase-producing Bacteroides species."	( Synergistic activity of cefsulodin combined with cefoxitin and sulbactam against Bacteroides species. Fu, KP; Kimble, EF; Konopka, EA; Zoganas, H, 1984)	0.27
"The antibacterial in vitro activity of piperacillin and tazobactam (in a concentration ratio of 8/1) was studied in combination with netilmicin or amikacin by a microtiter checkerboard assay against 162 strains of Enterobacteriaceae."	( [In vitro antibacterial activity of piperacillin-tazobactam in combination with netilmicin or amikacin against Enterobacteriaceae resistant to amoxicillin]. Chamard-Neuwirth, C; Cordin, X; Duez, JM; Kazmierczak, A; Pechinot, A; Siebor, E, 1995)	0.29
"The pharmacodynamics of dosage regimens of piperacillin alone or in combination with tazobactam against piperacillin-resistant or -susceptible bacteria were studied in an in vitro model of infection."	( Pharmacodynamics of piperacillin alone and in combination with tazobactam against piperacillin-resistant and -susceptible organisms in an in vitro model of infection. Dudley, MN; Gilbert, DH; Medeiros, AA; Pivarnik, P; Strayer, AH; Zinner, SH, 1994)	0.29
" pneumophila activity was observed for ceftriaxone (32 micrograms/ml), piperacillin (32 micrograms/ml), tazobactam alone (16 micrograms/ml), clavulanate alone (2 micrograms/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 micrograms/ml) or piperacillin (32/4 micrograms/ml)."	( In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species. Edelstein, MA; Edelstein, PH, 1994)	0.29
" However, strains expressing class A beta-lactamase were susceptible to cefodizime in combination with clavulanic acid."	( In vitro activity of cefodizime (HR-221) in combination with beta-lactamase inhibitors. Amicosante, G; Franceschini, N; Oratore, A; Perilli, M; Segatore, B; Setacci, D, 1993)	0.29
"The activity of piperacillin/tazobactam, ampicillin/sulbactam, imipenem and nafcillin alone and in combination with vancomycin was compared with vancomycin monotherapy against MRSA in test-tube time-kill studies and in infected fibrin clots."	( An evaluation of the bactericidal activity of ampicillin/sulbactam, piperacillin/tazobactam, imipenem or nafcillin alone and in combination with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in time-kill curves with infected fibrin Palmer, SM; Rybak, MJ, 1997)	0.3
"In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP)."	( Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group. Carbon, C; Carlet, J; Dupont, H, 2000)	0.31
"The bactericidal activity of moxifloxacin alone and in combination with cefepime or piperacillin-tazobactam against clinical isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii was evaluated by using time-kill methods and antimicrobial concentrations of one-half and one times the MIC."	( Synergistic activities of moxifloxacin combined with piperacillin-tazobactam or cefepime against Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii clinical isolates. Choi, MK; Fish, DN; Husain, M; Jung, R, 2004)	0.32
"This randomized, double-blind, multicenter study compared the efficacy and safety of piperacillin/tazobactam (P/T) and imipenem/cilastatin (IMP), both in combination with an aminoglycoside, in hospitalized patients with acute nosocomial pneumonia (NP)."	( Comparison of piperacillin/tazobactam and imipenem/cilastatin, both in combination with tobramycin, administered every 6 h for treatment of nosocomial pneumonia. Cooper, A; Joshi, M; Kassira, W; McCarthy, M; Metzler, M; Olvey, S, 2006)	0.33
"The mutant prevention concentrations (MPCs) of levofloxacin alone and in combination with ceftazidime, colistin (polymyxin E), meropenem, piperacillin-tazobactam, and tobramycin were established against Pseudomonas aeruginosa."	( Mutant prevention concentrations of levofloxacin alone and in combination with azithromycin, ceftazidime, colistin (Polymyxin E), meropenem, piperacillin-tazobactam, and tobramycin against Pseudomonas aeruginosa. Adam, HJ; Laing, N; Mayer, M; Zhanel, GG, 2006)	0.33
"We investigated the efficacy of Tachyplesin III alone or combined with piperacillin-tazobactam (TZP) to prevent biofilm formation in vitro and in a rat model of Pseudomonas aeruginosa ureteral stent infection."	( The antimicrobial peptide tachyplesin III coated alone and in combination with intraperitoneal piperacillin-tazobactam prevents ureteral stent Pseudomonas infection in a rat subcutaneous pouch model. Cirioni, O; Ghiselli, R; Giacometti, A; Giovanni, M; Kamysz, E; Kamysz, W; Minardi, D; Orlando, F; Parri, G; Saba, V; Scalise, G; Silvestri, C, 2007)	0.34
"To investigate the efficacy of piperacillin/tazobactam combined with indolicidin in the prevention of lethality in two rat models of polymicrobial peritonitis."	( Efficacy of the bovine antimicrobial peptide indolicidin combined with piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis. Abbruzzetti, A; Cirioni, O; Di Matteo, F; Ghiselli, R; Giacometti, A; Mocchegiani, F; Orlando, F; Saba, V; Scalise, G; Silvestri, C, 2008)	0.35
" For each model, all animals were randomized to receive isotonic sodium chloride solution intraperitoneally, 1 mg/kg indolicidin, 120 mg/kg piperacillin/tazobactam, and 1 mg/kg indolicidin combined with 120 mg/kg piperacillin/tazobactam."	( Efficacy of the bovine antimicrobial peptide indolicidin combined with piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis. Abbruzzetti, A; Cirioni, O; Di Matteo, F; Ghiselli, R; Giacometti, A; Mocchegiani, F; Orlando, F; Saba, V; Scalise, G; Silvestri, C, 2008)	0.35
"We investigated in vitro activities of piperacillin or cefoperazone alone and in combination with beta-lactamase inhibitors against Gram-negative bacilli."	( In vitro activities of piperacillin or cefoperazone alone and in combination with beta-lactamase inhibitors against gram-negative bacilli. Kuo, HY; Lin, ML; Liu, CY; Wang, FD; Yen, YF, 2009)	0.35
"ACHN-490 was tested alone and in combination with cefepime, doripenem, imipenem, or piperacillin-tazobactam in a synergy time-kill analysis against 25 Pseudomonas aeruginosa strains with different resistance phenotypes."	( Activity of ACHN-490 tested alone and in combination with other agents against Pseudomonas aeruginosa. Appelbaum, PC; Armstrong, ES; Kosowska-Shick, K; Kubo, A; Lin, G; Pankuch, GA, 2011)	0.37
"CXA-101, a novel oxyimino-aminothiazolyl cephalosporin, CXA-201 (CXA-101 combined with tazobactam), and various comparators were susceptibility tested by broth microdilution methods against 1,301 well-characterized clinical strains collected worldwide, including ceftazidime-resistant members of the family Enterobacteriaceae and Klebsiella pneumoniae carbapenemase (KPC)- and extended-spectrum β-lactamase (ESBL)-producing strains of Pseudomonas aeruginosa and Bacteroides fragilis."	( Antimicrobial activity of CXA-101, a novel cephalosporin tested in combination with tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis strains having various resistance phenotypes. Farrell, DJ; Jones, RN; Rhomberg, PR; Sader, HS, 2011)	0.37
" Herein, we describe dose fractionation studies designed to determine the exposure measure most predictive of tazobactam efficacy in combination with ceftolozane and the magnitude of this measure necessary for efficacy in a PK-PD in vitro infection model."	( Pharmacokinetics-pharmacodynamics of tazobactam in combination with ceftolozane in an in vitro infection model. Ambrose, PG; Bhavnani, SM; Bulik, CC; Castanheira, M; Forrest, A; Friedrich, LV; Jones, RN; Mendes, RE; Nicasio, AM; Okusanya, OO; Steenbergen, JN; VanScoy, B, 2013)	0.39
"We recently investigated the pharmacokinetics-pharmacodynamics (PK-PD) of tazobactam in combination with ceftolozane against an isogenic CTX-M-15-producing Escherichia coli triplet set, genetically engineered to transcribe different levels of blaCTX-M-15."	( Pharmacological basis of β-lactamase inhibitor therapeutics: tazobactam in combination with Ceftolozane. Ambrose, PG; Bhavnani, SM; Bulik, CC; Forrest, A; Friedrich, LV; Jones, RN; McCauley, J; Mendes, RE; Okusanya, OO; Steenbergen, JN; Vanscoy, B, 2013)	0.39
" aureus (VISA) are limited, but β-lactams in combination with vancomycin have shown synergistic activity against MRSA and VISA."	( Evaluation of vancomycin in combination with piperacillin-tazobactam or oxacillin against clinical methicillin-resistant Staphylococcus aureus Isolates and vancomycin-intermediate S. aureus isolates in vitro. Dilworth, TJ; Dodd, M; Mercier, RC; Ryan, K; Sliwinski, J, 2014)	0.4
"The post-β-lactamase-inhibitor effect (PBLIE) of tazobactam combined with ceftolozane was evaluated by time-kill assays on two clinical Escherichia coli strains producing CTX-M-15 with or without TEM-1."	( Post-β-lactamase-inhibitor effect of tazobactam in combination with ceftolozane on extended-spectrum-β-lactamase-producing strains. Jones, RN; Rhomberg, PR; Sader, HS, 2014)	0.4
" When combined with a fixed amount of 4 mg/liter tazobactam (current CLSI concentration used for susceptibility testing), 90% of the isolates would have an MIC of ≤4 mg/liter."	( In Vitro Activity of Ceftolozane Alone and in Combination with Tazobactam against Extended-Spectrum-β-Lactamase-Harboring Enterobacteriaceae. Melchers, MJ; Mouton, JW; van Mil, AC, 2015)	0.42
" Ceftazidime, cefepime, and piperacillin-tazobactam in combination with amikacin showed greater activity than found in combination with ciprofloxacin."	( In vitro activities of 21 antimicrobial agents alone and in combination with aminoglycosides or fluoroquinolones against extended-spectrum-β-lactamase-producing Escherichia coli isolates causing bacteremia. Cha, MK; Cho, SY; Chung, DR; Ha, YE; Kang, CI; Kim, SH; Peck, KR; Song, JH; Wi, YM, 2015)	0.42
"The present study evaluates the synergistic effect of sulbactam/tazobactam in combination with meropenem or colistin against multidrug resistant (MDR) Acinetobacter baumannii isolated from hospitalized patients from a tertiary care hospital in Saudi Arabia."	( A prospective evaluation of synergistic effect of sulbactam and tazobactam combination with meropenem or colistin against multidrug resistant Acinetobacter baumannii. Alyousef, AA; Alzahrani, AJ; Krishnappa, LG; Marie, MA; Mubaraki, MA, 2015)	0.42
"We have previously demonstrated the pharmacokinetic-pharmacodynamic (PK-PD) index best associated with the efficacy of tazobactam when used in combination with ceftolozane to be the percentage of the dosing interval during which tazobactam concentrations remained above a threshold value (%time>threshold)."	( Pharmacokinetics-Pharmacodynamics of Tazobactam in Combination with Piperacillin in an In Vitro Infection Model. Ambrose, PG; Bhavnani, SM; Bulik, CC; Castanheira, M; Forrest, A; Friedrich, LV; Jones, RN; Mendes, RE; Nicasio, AM; Okusanya, OO; Steenbergen, JN; VanScoy, BD, 2016)	0.43
"Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams."	( Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime. Burgess, DR; Burgess, DS; Cox, JN; Martin, CA; Rutter, WC, 2017)	0.46
" The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI)."	( Comparison of Rates of Nephrotoxicity Associated with Vancomycin in Combination with Piperacillin-Tazobactam Administered as an Extended versus Standard Infusion. Dubrovskaya, Y; Louie, E; Mousavi, M; Papadopoulos, J; Scipione, MR; Zapolskaya, T, 2017)	0.46
"Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI."	( Comparison of Rates of Nephrotoxicity Associated with Vancomycin in Combination with Piperacillin-Tazobactam Administered as an Extended versus Standard Infusion. Dubrovskaya, Y; Louie, E; Mousavi, M; Papadopoulos, J; Scipione, MR; Zapolskaya, T, 2017)	0.46
"Cystic fibrosis (CF) patients often receive prolonged courses of broad spectrum antibiotics, such as piperacillin-tazobactam or cefepime in combination with vancomycin and tobramycin."	( Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with vancomycin and tobramycin in pediatric cystic fibrosis patients. LeCleir, LK; Pettit, RS, 2017)	0.46
"AKI occurred in nearly 55% of patients with piperacillin-tazobactam therapy versus 13% of patients with cefepime therapy, which suggests cefepime may be preferred in combination with vancomycin and tobramycin for pediatric CF patients."	( Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with vancomycin and tobramycin in pediatric cystic fibrosis patients. LeCleir, LK; Pettit, RS, 2017)	0.46
"This single-center study evaluated the efficacy and safety of tazobactam/ceftolozane (TAZ/CTLZ) in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice."	( Efficacy and safety of tazobactam/ceftolozane in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice. Ishizawa, T; Kimura, K; Kinoshita, M; Kubo, S; Nishio, K; Ohira, G; Okada, T; Shinkawa, H; Shirai, D; Tanaka, S; Tani, N; Tauchi, J, 2023)	0.91
"This observational study demonstrated that TAZ/CTLZ in combination with metronidazole has a favorable effect without major drug-related adverse events for intraabdominal infection in the hepato-biliary-pancreatic field in clinical practice although the efficacy of TAZ/CTLZ may decrease in compromised patients."	( Efficacy and safety of tazobactam/ceftolozane in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice. Ishizawa, T; Kimura, K; Kinoshita, M; Kubo, S; Nishio, K; Ohira, G; Okada, T; Shinkawa, H; Shirai, D; Tanaka, S; Tani, N; Tauchi, J, 2023)	0.91

Excerpt	Reference	Relevance
" Sulbactam is poorly absorbed after oral administration and sulbactam/ampicillin is therefore administered parenterally, although another linked sulbactam-ampicillin compound, sultamicillin, has been developed which is well absorbed after oral administration."	( Sulbactam/ampicillin. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic use. Brogden, RN; Campoli-Richards, DM, 1987)	0.27
" There was a tendency for the new PA tablets to produce a higher peak serum level as well as greater bioavailability of mecillinam."	( Gastroscopic and pharmacokinetic evaluation of a new pivmecillinam tablet. Andersen, JT; Frederiksen, HJ; Hey, H, 1982)	0.26
" First-pass hydrolysis of this prodrug liberates equimolar proportions of sulbactam in plasma, saliva and urine is described and was used to determine the absolute bioavailability of sulbactam and ampicillin from sultamicillin in six normal male volunteers who each received a single 750 mg oral dose of sultamicillin or an iv dose of the equivalent amounts of ampicillin (441 mg) and sulbactam (294 mg)."	( Pharmacokinetics and bioavailability of sultamicillin estimated by high performance liquid chromatography. Bradbrook, ID; Cox, DA; Lees, LJ; Morrison, PJ; ROgers, HJ; Spector, RG, 1983)	0.27
" Bioavailability was 45 percent after the 250 mg dose and 38 percent after the 500 mg dose."	( Pharmacokinetics of amdinocillin and pivamdinocillin in normal volunteers. Christenson, JG; Francke, EL; Neu, HC; Ortiz-Neu, C; Srinivasan, S, 1983)	0.27
"5 times greater total bioavailability for ampicillin and sulbactam than when each was used individually."	( Pharmacokinetics of sultamicillin in mice, rats, and dogs. English, AR; Girard, D; Haskell, SL, 1984)	0.27
" The method has proved to be reliable and was used in bioavailability studies for the development of a new oral penicillin-V formulation."	( Determination of penicillin-V in human plasma by high-performance liquid chromatography and solid-phase extraction. Krauwinkel, WJ; Volkers-Kamermans, NJ, 1996)	0.29
" Generic substitutions within hospital formularies should consider parameters of in vitro activity, in addition to applied chemical analyses and measures of bioavailability to avoid potential adverse clinical consequences."	( Expanded studies of piperacillin/tazobactam formulations: variations among branded product lots and assessment of 46 generic lots. Jones, RN; Moet, GJ; Sader, HS; Watters, AA, 2009)	0.35

Excerpt	Relevance	Reference
"50 patients with a chronic disease of the bronchopulmonary system, within the therapy of an acute exacerbation received in addition to bronchosecretolytics, spasmolytic substances, and corticosterones the substance 'Spectacillin' in a dosage ranging from 2 to 6 grams per day during the period of 2 weeks."	( [Spectacillin-a new-developed multi-effective penicillin in treating chronic bronchoulmonary diseases author's transl]. Krause-Michel, B, 1975)	0.25
" Pivmecillinam was given in dosage of 400 mg (potency) per day which was one-fifth the dose of amoxicillin 2,000 mg (potency) per day."	( Clinical evaluation of pivmecillinam in intractable urinary-tract infections with complications. A comparative study with amoxicillin by a randomized double-blind technique. Akita, Y; Hara, S; Hikosaka, K; Hirooka, K; Ishigami, J; Kaneda, K; Kataoka, N; Kobayashi, M; Kuroda, K; Kuroda, M; Mita, T; Miyazaki, S; Nakatsuka, E; Okano, H; Ono, S; Suemitsu, H; Sugimoto, M; Takahashi, Y; Tanaka, K; Tanikaze, S; Terasoma, K; Tomioka, S; Ueharaguchi, H; Yasumuro, T, 1977)	0.26
" Dosage alterations for creatinine clearance values less than 40 ml/min are recommended."	( Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease. Dutta, A; Faulkner, R; Greene, DS; Halstenson, CE; Haynes, J; Johnson, CA; Kelloway, JS; Shapiro, BE; Tonelli, A; Zimmerman, SW, 1992)	0.28
" The dosage regimen was 4 g piperacillin/500 mg tazobactam Q8H."	( Piperacillin/tazobactam in the treatment of serious acute soft tissue infection. Ansari, A; Douglas, JG; Gould, IM; Harvey, G; Reid, TM; Smith, CC, 1991)	0.28
" Different doses of piperacillin and tazobactam, as single agents and combined (8:1 ratio; dosage range, 40/5 to 200/25 mg/kg per h), and of ceftriaxone were given to experimentally infected rabbits by intravenous bolus injection followed by a 5-h constant infusion."	( Evaluation of piperacillin-tazobactam in experimental meningitis caused by a beta-lactamase-producing strain of K1-positive Escherichia coli. Gunderson, D; Kennedy, SL; Kern, W; Sachdeva, M; Sande, ER; Täuber, MG, 1990)	0.28
" Therefore, sulbactam should predictably increase the antimicrobial spectrum and clinical effectiveness of cefoperazone against nosocomial and other pathogens such as the plasmid-containing enteric bacilli, Bacteroides species and Acinetobacter species, and possibly provide the opportunity to reduce dosage schedules for infecting species already susceptible to cefoperazone alone."	( In vitro antimicrobial activity of cefoperazone-sulbactam combinations against 554 clinical isolates including a review and beta-lactamase studies. Barry, AL; Jones, RN; Thornsberry, C; Wilson, HW, 1985)	0.27
"5 or 25 mg/kg were infused over 3 min, and in previously healthy children, mean peak plasma concentrations 5 min after dosing were 71 and 163 micrograms/ml, respectively."	( Single-dose pharmacokinetics of intravenous sulbactam in pediatric patients. Guenin, K; Schaad, UB; Straehl, P, )	0.13
" The aims were to determine an appropriate dosage regimen and to study the pharmacokinetics."	( Pharmacokinetic study of sulbactam and ampicillin administered concomitantly by intraarterial or intravenous infusion in the newborn. Cockburn, F; McAllister, TA; Sutton, AM; Turner, TL, )	0.13
" Sulbactam/ampicillin was administered im or iv at a dosage of 3-9 g/day depending on the site and severity of the infection."	( Clinical efficacy and safety of sulbactam/ampicillin in patients suffering from chronic liver disease. Barba, D; Esposito, S; Galante, D; Ruffilli, MP, 1987)	0.27
" Based on the relationship between creatinine clearance and plasma clearance of mecillinam, and considering that the drug is a relatively non-toxic bactericidal antibiotic, the following dosage adjustment scheme is proposed: glomerular filtration rate over 30 ml/min: normal dosage; 10-30 ml/min: 50% of normal dosage; under 10 ml/min: 25% of normal dosage."	( Single-dose kinetics and dosage of mecillinam in renal failure and haemodialysis. Schapira, A, )	0.13
" Two dosage schedules were investigated, both resulting in the same total daily dosage (1500 mg sultamicillin)."	( Sultamicillin (CP-49, 952): evaluation of two dosage schedules in urinary infection. Ball, AP; Fox, C; Ghosh, D, 1984)	0.27
" SBT/CPZ was given to total 43 cases at a mean daily dosage of 80."	( [Fundamental and clinical studies of sulbactam/cefoperazone in the pediatric field]. Fujimoto, T; Ishimoto, K; Koga, T; Motohiro, T; Nishiyama, T; Sakata, Y; Shimada, Y; Tanaka, K; Tominaga, K; Tomita, N, 1984)	0.27
" Based on these results, SBT/CPZ is considered to be a highly effective antibiotic with clinical efficacy in obstetric and gynecological infections in the daily dosage of 2 g given in two divided doses."	( [Experience with sulbactam/cefoperazone in the field of obstetrics and gynecology]. Hirai, S; Iida, S; Kohara, T; Matsui, Y; Noda, M, 1984)	0.27
" The dosage of pivamdinocillin in adults was 400 to 800 mg, every 6 hours, for 10 to 16 days; dosage in children was half this amount for 11 to 15 days."	( Management of enteric fever with amdinocillin. Ball, AP; Geddes, AM, 1983)	0.27
" One patient in each dosage group discontinued the medication because of severe diarrhoea."	( Clinical, bacteriological and pharmacokinetic results from an open trial of sultamicillin in patients with acute exacerbations of chronic bronchitis. Davies, BI; Maesen, FP; van Noord, JA, 1984)	0.27
" With some antibiotic-inhibitor combinations, it may be possible to extend the dosage interval if an adequate amount of inhibitor is provided over the course of therapy."	( Combination beta-lactam and beta-lactamase-inhibitor therapy: pharmacokinetic and pharmacodynamic considerations. Dudley, MN, 1995)	0.29
" Blood samples and cumulative bile secretion were collected every 30 min, and liver fragments were isolated at the end of each experiment for dosage purposes."	( Biliary elimination and hepatic disposition of an association of piperacillin and tazobactam: experimental evaluation. Blickle, JF; Brogard, JM; Caro-Sampara, F; Jehl, F; Westphal, JF, 1994)	0.29
" In the TAZ/PIPC, maternal toxicity (decreased food consumption) was observed at 200 mg/kg and above dosage groups."	( [Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam(1)--Fertility and general reproduction study in rats with intraperitoneal administration]. Christian, MS; Hoberman, AM; Lochry, EA; Sato, T, 1994)	0.29
" In the TAZ, maternal toxicity (decreased food consumption) was observed at all dosage groups during perinatal period."	( [Reproductive and developmental toxicity studies of tazobactam/piperacillin or tazobactam (3)--Perinatal and postnatal study in rats with intraperitoneal administration]. Christian, MS; Hoberman, AM; Sato, T, 1994)	0.29
"The pharmacodynamics of dosage regimens of piperacillin alone or in combination with tazobactam against piperacillin-resistant or -susceptible bacteria were studied in an in vitro model of infection."	( Pharmacodynamics of piperacillin alone and in combination with tazobactam against piperacillin-resistant and -susceptible organisms in an in vitro model of infection. Dudley, MN; Gilbert, DH; Medeiros, AA; Pivarnik, P; Strayer, AH; Zinner, SH, 1994)	0.29
"Piperacillin/tazobactam, at a dosage of 4 g/500 mg every 8 h, was administered intravenously to 217 patients with complicated urinary tract infections."	( Piperacillin/tazobactam in complicated urinary tract infections. Nowé, P, 1994)	0.29
" An increase in the tazobactam dosage within the combination (80:25 mg/kg/h) was required in order to obtain a significantly faster elimination of viable organisms from the CSF (-0."	( Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase. Decazes, JM; Gutmann, L; Kitzis, MD; Leleu, G; Vallois, JM, 1994)	0.29
" At the dosage used piperacillin/tazobactam was as safe as, and statistically more effective than, imipenem/cilastatin in the treatment of intra-abdominal infections caused by sensitive organisms."	( A randomized multicenter trial of piperacillin/tazobactam versus imipenem/cilastatin in the treatment of severe intra-abdominal infections. Swedish Study Group. Eklund, AE; Nord, CE, 1993)	0.29
" Piperacillin and tazobactam concentrations can be adjusted by applying prolonged dosing intervals in renal patients."	( Pharmacokinetics of piperacillin, tazobactam and its metabolite in renal impairment. Dalla Costa, T; Derendorf, H, 1996)	0.29
" The drug was given to an underweight 18-year-old woman, at the usual dosage of 4/0."	( Reversible bone marrow depression by high-dose piperacillin/tazobactam. Aguirre, C; Barreiro, G; Ruiz-Irastorza, G, 1996)	0.29
" Serum bactericidal titers were determined and used to calculate the duration of measurable bactericidal activity over the dosing interval of each of the regimens against two clinical isolates of Bacillus fragilis, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa."	( Comparison of the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillin-sulbactam against clinical isolates of Bacteroides fragilis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Klepser, ME; Marangos, MN; Nicolau, DP; Nightingale, CH; Quintiliani, R; Zhu, Z, 1997)	0.3
" pneumoniae may be highly dependent on dosing regimens, even for a specific organism and site of infection."	( Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae. Eliopoulos, GM; Moellering, RC; Thauvin-Eliopoulos, C; Tripodi, MF, 1997)	0.3
"In CVVH dependent patients, pip/taz fixed drug preparations can be used initially, but the pip dosage should be increased relative to that of taz (or interval-adjusted) to prevent cumulation of taz, as compared to the active antimicrobial agent pip."	( Pharmacokinetics of piperacillin and tazobactam in critically ill patients with renal failure, treated with continuous veno-venous hemofiltration (CVVH). Mulder, PO; Stegeman, CA; Uges, DR; van der Werf, TS; Zijlstra, JG, 1997)	0.3
" bolus multiple dose, using different dose ratio combinations (1:4, 1:8, 1:16) and dosing regimens, ranging from once-a-day to 4 times a day."	( Pharmacokinetic-pharmacodynamic modelling of the in vitro antiinfective effect of piperacillin-tazobactam combinations. Dalla Costa, T; Derendorf, H; Nolting, A; Rand, K, 1997)	0.3
"The PK-PD model allowed a detailed evaluation of the dosing regimens investigated."	( Pharmacokinetic-pharmacodynamic modelling of the in vitro antiinfective effect of piperacillin-tazobactam combinations. Dalla Costa, T; Derendorf, H; Nolting, A; Rand, K, 1997)	0.3
" The percentage of time that plasma concentrations remained above the MIC (T > MIC) for each organism and dosage regimen was calculated."	( Pharmacokinetics and pharmacodynamics of two multiple-dose piperacillin-tazobactam regimens. Danziger, LH; Occhipinti, DJ; Pendland, SL; Rodvold, KA; Rypins, EB; Schoonover, LL, 1997)	0.3
" This raises the question of the pertinence of the dosage regimen."	( Influence of pregnancy on the pharmacokinetic behaviour and the transplacental transfer of the piperacillin-tazobactam combination. Bourget, P; Fernandez, H; Lesne-Hulin, A; Sertin, A; Van Peborgh, P; Ville, Y, 1998)	0.3
" Optimal dosage regimens of beta-lactamase inhibitors will provide mean concentrations of beta-lactamase inhibitor at or above those used in in-vitro testing."	( Beta-lactam/beta-lactamase inhibitor combinations: pharmacodynamic considerations and possible role in the management of bacterial infections in the neutropenic host. Dudley, MN; Okereke, C, 1998)	0.3
" Under base-case conditions, our pharmacoeconomic analysis showed that I/C was a cost-effective alternative to P/T at the dosage regimens studied."	( Cost-minimization analysis of piperacillin/tazobactam versus imipenem/cilastatin for the treatment of serious infections: a Canadian hospital perspective. Bryce, EA; Frighetto, LO; Jewesson, PJ; Marra, CA; Marra, FO; Reynolds, RP; Sleigh, KM; Stiver, HG, 1999)	0.3
"A population pharmacokinetic (PK) analysis was conducted to determine if piperacillin and tazobactam exhibited linear or nonlinear PKs and if incremental changes in the daily dosage of piperacillin affected tazobactam PKs."	( Piperacillin and tazobactam exhibit linear pharmacokinetics after multiple standard clinical doses. Auclair, B; Ducharme, MP, 1999)	0.3
" In patients with intra-abdominal infections, clinical and bacteriological response rates were significantly higher with piperacillin/tazobactam than with imipenem/cilastatin (administered at a dosage lower than is recommended in countries outside Scandinavia)."	( Piperacillin/tazobactam: an updated review of its use in the treatment of bacterial infections. Markham, A; Perry, CM, 1999)	0.3
" The T>MIC was calculated as percentage of the dosing interval in which free concentrations exceeded the weighted geometric mean MIC90."	( Comparison of five beta-lactam antibiotics against common nosocomial pathogens using the time above MIC at different creatinine clearances. Kays, MB, 1999)	0.3
"Tazobactam/piperacillin (total daily dosage of 13."	( Cost efficacy of tazobactam/piperacillin versus imipenem/cilastatin in the treatment of intra-abdominal infection. Daschner, F; Dietrich, ES; Ebner, W; Schubert, B, 2001)	0.31
"To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin-tazobactam against commonly encountered pathogens."	( Pharmacokinetic and pharmacodynamic evaluation of two dosing regimens for piperacillin-tazobactam. Capitano, B; Kim, MK; Mattoes, HM; Nicolau, DP; Nightingale, CH; Quintiliani, R; Xuan, D, 2002)	0.31
"The two dosing regimens for piperacillin-tazobactam were administered intravenously in crossover design."	( Pharmacokinetic and pharmacodynamic evaluation of two dosing regimens for piperacillin-tazobactam. Capitano, B; Kim, MK; Mattoes, HM; Nicolau, DP; Nightingale, CH; Quintiliani, R; Xuan, D, 2002)	0.31
"Although intermittent bolus dosing is currently the standard of practice for many antimicrobial agents, beta-lactams exhibit time-dependent bacterial killing."	( Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam when administered by continuous infusion and intermittent dosing. Burgess, DS; Waldrep, T, 2002)	0.31
" aeruginosa infections due to the higher established breakpoint, these data suggest a high probability of achieving adequate drug exposure against susceptible isolates with this dosing regimen."	( Pharmacodynamic profiling of continuously infused piperacillin/tazobactam against Pseudomonas aeruginosa using Monte Carlo analysis. Kuti, JL; Nicolau, D; Nightingale, CH; Quintiliani, R, 2002)	0.31
" Since time above the MIC (T>MIC) is the pharmacokinetic-pharmacodynamic (PK-PD) measure that best correlates with in vivo activity of beta-lactams, a stochastic model was used to predict the probability of PK-PD target attainment ranging from 30 (P30) to 70% (P70) T>MIC, for standard dosing regimens of both piperacillin-tazobactam and cefepime against Escherichia coli and Klebsiella pneumoniae ESBL phenotypes."	( Pharmacokinetics-pharmacodynamics of cefepime and piperacillin-tazobactam against Escherichia coli and Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases: report from the ARREST program. Ambrose, PG; Bhavnani, SM; Jones, RN, 2003)	0.32
" Thirty timed observations were made for each of the dosing formulations."	( Cost analysis of continuous versus intermittent infusion of piperacillin-tazobactam: a time-motion study. Florea, NR; Geissler, EC; Kotapati, S; Kuti, JL; Nicolau, DP; Nightingale, CH, 2003)	0.32
" Dose reduction because of impaired renal function was required in the intermittent dosing group for 5 of 12 patients compared with 1 of 12 patients in the continuous infusion group."	( Pharmacokinetics of piperacillin-tazobactam: intermittent dosing versus continuous infusion. Ackermann, T; Bertram, N; Buck, C; Derendorf, H; Paar, WD; Sauerbruch, T, 2005)	0.33
" The desired proportion of the dosing interval that the concentration remains above the MIC (%T>MIC) for the intermittent bolus regimens was >/=40% for piperacillin/tazobactam and >/=60% for cefepime."	( Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms. Burgess, DS; Frei, CR; Reese, AM, 2005)	0.33
" The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated."	( Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program. Kuti, JL; Nicolau, DP; Sun, HK, 2005)	0.33
"Once daily IV/PO moxifloxacin monotherapy was as least as effective as standard IV piperacillin-tazobactam/PO amoxicillin-clavulanate dosed multiple times daily for the treatment of cIAIs."	( Randomized controlled trial of moxifloxacin compared with piperacillin-tazobactam and amoxicillin-clavulanate for the treatment of complicated intra-abdominal infections. Choudhri, S; Herrington, J; Malangoni, MA; Pertel, P; Song, J, 2006)	0.33
" Ertapenem is a long-acting 1-beta-methyl parenteral group 1 carbapenem antibiotic that has a broad antibacterial spectrum and once-daily dosing supported by clinical studies."	( Bactericidal activity of ertapenem against major intra-abdominal pathogens. Borbone, S; Cascone, C; Mezzatesta, ML; Santagati, M; Stefani, S, 2006)	0.33
" In an effort to improve clinical outcomes, an extended-infusion dosing scheme for piperacillin-tazobactam therapy was devised using a Monte Carlo simulation and was adopted into clinical practice at Albany Medical Center (Albany, New York)."	( Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Drusano, GL; Lodise, TP; Lomaestro, B, 2007)	0.34
" None of the patients dosed with piperacillin/tazobactam was adequately protected for the duration of their surgery and adequate prophylaxis was only evident in four of the nine patients administered cefalotin."	( Inadequate antimicrobial prophylaxis during surgery: a study of beta-lactam levels during burn debridement. Cross, SE; Dalley, AJ; Lipman, J; Roberts, MS; Rudd, M; Venkatesh, B, 2007)	0.34
"These results suggest a need to review antibiotic prophylaxis dosage regimens for burns surgery and the adoption of regimens that will minimize the risk of infection in this high-risk patient group."	( Inadequate antimicrobial prophylaxis during surgery: a study of beta-lactam levels during burn debridement. Cross, SE; Dalley, AJ; Lipman, J; Roberts, MS; Rudd, M; Venkatesh, B, 2007)	0.34
" The purpose of this analysis is to describe the basis for the dosing recommendations in this age group."	( Optimising piperacillin/tazobactam dosing in paediatrics. Alexander, JJ; Gobburu, JV; Imoisili, MA; Korth-Bradley, JM; Tornøe, CW; Tworzyanski, JJ, 2007)	0.34
"To report pharmacokinetic alterations and optimal dosing of piperacillin/tazobactam in an obese patient."	( Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. Adeyemi, OA; Montevecchi, M; Newman, D; Nicolau, DP; Noskin, GA; Postelnick, MJ; Scheetz, MH, 2007)	0.34
"Pathogens with elevated MICs may require altered dosing schemes with piperacillin/tazobactam."	( Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. Adeyemi, OA; Montevecchi, M; Newman, D; Nicolau, DP; Noskin, GA; Postelnick, MJ; Scheetz, MH, 2007)	0.34
"To compare conventional intermittent dosing regimens of piperacillin-tazobactam with prolonged and continuous infusions to determine the optimal dosing scheme against a local Pseudomonas aeruginosa population."	( Optimal dosing of piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion? Kim, A; Kuti, JL; Nicolau, DP; Sutherland, CA, 2007)	0.34
"We simulated serum concentration-time profiles at steady state for several piperacillin-tazobactam dosing regimens, including intermittent, prolonged, and continuous infusions."	( Optimal dosing of piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion? Kim, A; Kuti, JL; Nicolau, DP; Sutherland, CA, 2007)	0.34
" Thus, the selection of dosing strategy depends on the availability of intravenous access versus the convenience of once-daily administration."	( Optimal dosing of piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion? Kim, A; Kuti, JL; Nicolau, DP; Sutherland, CA, 2007)	0.34
"Assesment of dosage deviations of three ss-lactam antibiotics eliminated through the kidneys (meropenem, piperacillin/tazobactam and cefepime) by comparison of two prediction formulae, Cockroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) with 24 h urinary creatinine clearance (CrCl(24h)), as a reference method."	( [The impact of different renal function measuring methods on the dosages of meropenem, piperacillin/tazobactam and cefepime in critically ill patients]. Diego del Río, E; Gratacós Santanach, L; Ribas Sala, J; Soy Muner, D, )	0.13
" Dosage discrepancies for each antibiotic based on CG y MDRD were studied in reference to CrCl(24h) by percentage agreement and weighted kappa."	( [The impact of different renal function measuring methods on the dosages of meropenem, piperacillin/tazobactam and cefepime in critically ill patients]. Diego del Río, E; Gratacós Santanach, L; Ribas Sala, J; Soy Muner, D, )	0.13
" The pharmacodynamic target was free piperacillin concentration remaining above the MIC for 50% of the dosing interval."	( Steady-state pharmacokinetics and pharmacodynamics of piperacillin/tazobactam administered by prolonged infusion in hospitalised patients. Cheatham, SC; Kays, MB; Shea, KM; Smith, DW; Sowinski, KM; Wack, MF, 2009)	0.35
"With increasing antibiotic resistance in gram-negative pathogens, dosing strategies that optimize pharmacodynamic parameters of currently available antibiotics play an important role in treatment."	( Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulation and steady-state pharmacokinetic data from hospitalized patients. Rotschafer, JC; Ullman, M, 2009)	0.35
"To compare the pharmacodynamics of several dosing regimens of piperacillin/tazobactam administered by intermittent and prolonged infusion using pharmacokinetic data from hospitalized patients."	( Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Cheatham, SC; Kays, MB; Shea, KM; Smith, DW; Sowinski, KM; Wack, MF, 2009)	0.35
"This study examined the effect of various levels of renal impairment on the probability of achieving free drug concentrations that exceed the MIC for 50% of the dosing interval (50% fT > MIC) for traditional and extended-infusion piperacillin-tazobactam (TZP) dosing strategies."	( Identification of optimal renal dosage adjustments for traditional and extended-infusion piperacillin-tazobactam dosing regimens in hospitalized patients. Drusano, GL; Lodise, TP; Patel, N; Scheetz, MH, 2010)	0.36
" With both longer PLIE and PASME, longer dosing interval should be recommended."	( [Post antibiotic, post beta-lactamase inhibitor and post antibiotic sub-MIC effect of ceftriaxone/tazobactam on beta-lactamase-producing Escherichia coli in vitro]. Chen, SW; Liu, XK; Wu, HY; Zhang, LL; Zhang, SC, 2009)	0.35
" The dosage was adjusted when the serum piperacillin concentration either fell below 4x the drug's minimum inhibitory concentration (MIC) for the causative agent or exceeded the toxic threshold of 150 mg/L."	( Daily serum piperacillin monitoring is advisable in critically ill patients. Blondiaux, N; Courcol, RJ; Durocher, A; Favory, R; Nseir, S; Onimus, T; Roussel-Delvallez, M; Wallet, F, 2010)	0.36
" There was near-complete cessation of the every-6-hour dosage interval and a marked increase in the every-8-hour and every-12-hour dosage intervals."	( Implementation of an extended-infusion piperacillin-tazobactam program at an urban teaching hospital. Caquelin, C; Glowacki, RC; Grasso, AE; Itokazu, GS; Schwartz, DN; Xamplas, RC, 2010)	0.36
" Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 × MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 μg/mL), 45% for ceftazidime (MIC = 32 μg/mL), 34% for cefepime (MIC = 32 μg/mL), and 33% for piperacillin-tazobactam (MIC = 64 μg/mL)."	( Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. De Backer, D; Delattre, I; Dugernier, T; Jacobs, F; Laterre, PF; Layeux, B; Spapen, H; Taccone, FS; Vincent, JL; Wallemacq, P; Wittebole, X, 2010)	0.36
" Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock."	( Insufficient β-lactam concentrations in the early phase of severe sepsis and septic shock. De Backer, D; Delattre, I; Dugernier, T; Jacobs, F; Laterre, PF; Layeux, B; Spapen, H; Taccone, FS; Vincent, JL; Wallemacq, P; Wittebole, X, 2010)	0.36
" Dialysis equipment and prescriptions have gradually changed over time, raising concern that current drug dosing recommendations in the literature may result in underdosing of antibiotics."	( Therapeutic drug monitoring of piperacillin-tazobactam using spent dialysate effluent in patients receiving continuous venovenous hemodialysis. Bauer, SR; Butler, R; Connor, MJ; Fissell, WH; Groszek, J; Hofmann, CL; Rehm, SJ; Salem, C, 2011)	0.37
" This possible loss of bactericidal effect should be brought to the attention of physicians and may require high dosing regimens for the treatment of severe infections."	( In vitro efficiency of the piperacillin/tazobactam combination against inhibitor-resistant TEM- and complex mutant TEM-producing clinical strains of Escherichia coli. Bonnet, R; Delmas, J; Gibold, L; Krebs, M; Mirande, C; Robin, F, 2011)	0.37
"Pharmacodynamic dosing using extended-infusion piperacillintazobactam demonstrated favorable outcomes, including mortality, when compared with nonextended-infusion, similar-spectrum [H9252]-lactams in the treatment of patients with documented gram-negative infections."	( The Retrospective Cohort of Extended-Infusion Piperacillin-Tazobactam (RECEIPT) study: a multicenter study. Cappelletty, DM; Yost, RJ, 2011)	0.37
" Piperacillin/tazobactam (TZP) is currently recommended in the empirical treatment of VAP, but intermittent dosing may result in inadequate serum concentrations."	( Continuous infusion of piperacillin/tazobactam in ventilator-associated pneumonia: a pilot study on efficacy and costs. Duszynska, W; Hurkacz, M; Kowalska-Krochmal, B; Kübler, A; Switala, M; Taccone, FS, 2012)	0.38
"Articles evaluating the administration of piperacillin/tazobactam to adults and comparing at least 2 dosing regimens (1 of which included the traditional, manufacturer-recommended 30-minute infusion; the other, a prolonged or continuous infusion strategy) were included."	( Evaluating outcomes associated with alternative dosing strategies for piperacillin/tazobactam: a qualitative systematic review. Chow, I; Ensom, MH; Mabasa, VH; Mah, GT, 2012)	0.38
" Retrospective studies indicate that critical care patients are the subgroup most likely to benefit from these dosing strategies."	( Evaluating outcomes associated with alternative dosing strategies for piperacillin/tazobactam: a qualitative systematic review. Chow, I; Ensom, MH; Mabasa, VH; Mah, GT, 2012)	0.38
"Current recommendations for piperacillin-tazobactam dosing in patients receiving continuous renal replacement therapy originate from studies with relatively few patients and lower continuous renal replacement therapy doses than commonly used today."	( Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Bauer, SR; Connor, MJ; Fissell, WH; Groszek, J; Salem, C; Taylor, ME; Tolwani, AJ; Wei, P, 2012)	0.38
" The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear."	( Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses. Benziger, D; Friedland, I; Hershberger, E; Miller, B; Trinh, M, 2012)	0.38
"We obtained data from 40 dosing intervals and observed wide variability in trough concentrations (6."	( Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study. Bellomo, R; Cole, L; Lipman, J; Liu, X; Nair, P; Roberts, DM; Roberts, JA; Roberts, MS, 2012)	0.38
" Here, empirical dosing of antibiotics failed to achieve the target trough antibiotic concentration during 25% of the dosing intervals."	( Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study. Bellomo, R; Cole, L; Lipman, J; Liu, X; Nair, P; Roberts, DM; Roberts, JA; Roberts, MS, 2012)	0.38
" Monte Carlo simulations (MCSs) were used to determine the most effective administration schedule to ensure that free piperacillin concentrations were above the MIC for at least 50% of the dosing interval (50% fT>MIC) and to quantify the extent of the nonlinear clearance."	( Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections. Butterfield, JM; Drusano, GL; Felton, TW; Hope, WW; Kwa, AL; Lodise, TP; Lomaestro, BM, 2012)	0.38
"The goal of this study was to determine the feasibility of using an extended-infusion PT dosing strategy as the standard of care in a children's hospital."	( System-wide implementation of the use of an extended-infusion piperacillin/tazobactam dosing strategy: feasibility of utilization from a children's hospital perspective. Cox, EG; Kays, MB; Knoderer, CA; Nichols, KR, 2012)	0.38
" After institution of an extended-infusion PT dosing protocol as the standard dosing option, patients receiving PT were prospectively assessed for presence of and reasons for changes in dosing regimen."	( System-wide implementation of the use of an extended-infusion piperacillin/tazobactam dosing strategy: feasibility of utilization from a children's hospital perspective. Cox, EG; Kays, MB; Knoderer, CA; Nichols, KR, 2012)	0.38
" Dosing errors, which were voluntarily reported, were infrequent (1."	( System-wide implementation of the use of an extended-infusion piperacillin/tazobactam dosing strategy: feasibility of utilization from a children's hospital perspective. Cox, EG; Kays, MB; Knoderer, CA; Nichols, KR, 2012)	0.38
"Results of this study suggest that extended-infusion PT dosing was feasible in this specific children's hospital."	( System-wide implementation of the use of an extended-infusion piperacillin/tazobactam dosing strategy: feasibility of utilization from a children's hospital perspective. Cox, EG; Kays, MB; Knoderer, CA; Nichols, KR, 2012)	0.38
" Mean maximum concentration and AUC from time 0 to the end of the dosing interval (AUC(0-τ)) for ceftolozane in ELF were 21."	( Intrapulmonary penetration of ceftolozane/tazobactam and piperacillin/tazobactam in healthy adult subjects. Chandorkar, G; Gotfried, MH; Huntington, JA; Rodvold, KA; Umeh, O, 2012)	0.38
" Therefore, the saturable elimination and its impact on the choice of optimal dosage regimens were quantified."	( Population pharmacokinetics of piperacillin at two dose levels: influence of nonlinear pharmacokinetics on the pharmacodynamic profile. Bulitta, JB; Drusano, GL; Holzgrabe, U; Kinzig, M; Kirkpatrick, CM; Landersdorfer, CB; Sörgel, F; Stephan, U, 2012)	0.38
" The ceftazidime and cefepime dosing ranges from the literature are 200-400 mg/kg/day divided every 6-8 hr, maximum 8-12 g/day, and 150-200 mg/kg/day divided every 6-8 hr, up to 6-8 g/day, respectively."	( Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. cephalosporins and penicillins. Ampofo, K; Sherwin, CM; Spigarelli, MG; Stockmann, C; Waters, CD; Young, DC; Zobell, JT, 2013)	0.39
" We successfully matched 173 pairs of patients according to whether they received continuous or conventional intermittent dosing of piperacillin/tazobactam, using a propensity score to adjust for confounding variables."	( Continuous infusion of piperacillin/tazobactam in septic critically ill patients--a multicenter propensity matched analysis. Bento, L; Estilita, J; Gonçalves-Pereira, J; Gouveia, J; Janeiro, S; Monteiro, C; Oliveira, BS; Paulino, C; Póvoa, P; Salgueiro, A; Vieira, A, 2012)	0.38
"Studies evaluating the outcomes of an extended-infusion (EI) piperacillin-tazobactam dosing strategy in specific cohorts of critically ill patients are lacking."	( Outcomes of extended-infusion piperacillin-tazobactam: a retrospective analysis of critically ill patients. Lee, GC; Liou, H; Neldner, K; Quan, CF; Yee, R, 2012)	0.38
" Pharmacokinetic parameters were estimated and 5000-patient Monte Carlo simulations were performed for four prolonged-infusion dosing regimens."	( Steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients. Cheatham, SC; Chung, CE; Fleming, MR; Healy, DP; Humphrey, ML; Kays, MB; Shea, KM, 2013)	0.39
" Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations."	( Molecular Adsorbent Recirculating System (MARS(®)) removal of piperacillin/tazobactam in a patient with acetaminophen-induced acute liver failure. Argento, AC; Heavner, MS; Ruggero, MA; Topal, JE, 2013)	0.39
" Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011)."	( Prolonged infusion antibiotics for suspected gram-negative infections in the ICU: a before-after study. Arnold, HM; Hampton, NB; Hoban, A; Hoffmann, J; Hollands, JM; Juang, PH; Kollef, MH; McCormick, S; Micek, ST; Reichley, RM; Skrupky, LP; Smith, JR, 2013)	0.39
"To develop population pharmacokinetic (PK) models for piperacillin/tazobactam in neonates and infants of less than 2 months of age in order to determine the appropriate dosing regimen and provide a rational basis for the development of preliminary dosing guidelines suitable for this population."	( Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants. Cao, D; Cao, Y; Chen, C; Chen, Y; Li, Q; Li, Z; Shi, W; Wang, Y; Wu, D; Zhu, Y, 2013)	0.39
" The dosing strategy 44."	( Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants. Cao, D; Cao, Y; Chen, C; Chen, Y; Li, Q; Li, Z; Shi, W; Wang, Y; Wu, D; Zhu, Y, 2013)	0.39
" The results indicated that higher doses or more frequent dosing regimens may be required for controlling infection in this population in NICU."	( Population pharmacokinetics of piperacillin/tazobactam in neonates and young infants. Cao, D; Cao, Y; Chen, C; Chen, Y; Li, Q; Li, Z; Shi, W; Wang, Y; Wu, D; Zhu, Y, 2013)	0.39
"Correct antibiotic dosing remains a challenge for the clinician."	( Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Carlier, M; Carrette, S; De Waele, JJ; Decruyenaere, J; Depuydt, P; Hoste, E; Lipman, J; Roberts, JA; Stove, V; Verstraete, A; Wallis, SC, 2013)	0.39
"Infusion pump characteristics and tubing residuals can affect extended-infusion piperacillin-tazobactam dosing strategies."	( Using higher doses to compensate for tubing residuals in extended-infusion piperacillin-tazobactam. Bhowmick, T; Gross, A; Lam, WJ; Vanschooneveld, TC; Weinstein, MP, 2013)	0.39
" In these studies, the experimental duration (10 days), ceftolozane-tazobactam dose ratio (2:1), and dosing interval (every 8 h) were selected to approximate those expected to be used clinically."	( Relationship between ceftolozane-tazobactam exposure and drug resistance amplification in a hollow-fiber infection model. Ambrose, PG; Bhavnani, SM; Castanheira, M; Forrest, A; Friedrich, LV; Jones, RN; McCauley, J; Mendes, RE; Okusanya, OO; Steenbergen, J; Vanscoy, B, 2013)	0.39
"The physical compatibility of vancomycin and piperacillin sodium-tazobactam at dosing concentrations commonly administered during prolonged infusions was studied."	( Physical compatibility of vancomycin and piperacillin sodium-tazobactam at concentrations typically used during prolonged infusions. Leung, E; Ly, SC; Scheetz, MH; Venkatesan, N, 2013)	0.39
" The probability of target attainment for 50% or higher of the dosing interval during which free (unbound) drug concentrations exceeded the minimum inhibitory concentration (%fT > MIC) of likely pathogens was calculated for piperacillin at various MICs."	( Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Allen, N; Fish, DN; Newell, M; Rafferty, KD; Sturm, AW; Toschlog, E; Waibel, B, 2014)	0.4
"5 g intravenously every 6 hours was shown to be an appropriate dosage for this study population."	( Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Allen, N; Fish, DN; Newell, M; Rafferty, KD; Sturm, AW; Toschlog, E; Waibel, B, 2014)	0.4
" The objectives of this study were to characterize the pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with CF and derive optimized piperacillin/tazobactam dosing recommendations."	( Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations. Beegle, S; Butterfield, JM; Farkas, J; Lodise, TP; Pai, MP; Rosen, J, 2014)	0.4
" Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for regimens where free piperacillin concentrations were above the MIC for at least 50% of the dosing interval."	( Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations. Beegle, S; Butterfield, JM; Farkas, J; Lodise, TP; Pai, MP; Rosen, J, 2014)	0.4
" Results of our simulation revealed that piperacillin/tazobactam dosed at 3-4 g for 30 min every 6-8 h led to <90% PTA against MIC values >4 mg/L."	( Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations. Beegle, S; Butterfield, JM; Farkas, J; Lodise, TP; Pai, MP; Rosen, J, 2014)	0.4
"Piperacillin/tazobactam is a frequently prescribed antibiotic in pediatric intensive care units, but pharmacokinetic data to justify the optimal piperacillin/tazobactam dosing regimen are sparse in critically ill children."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill young children. Cies, JJ; Kuti, JL; Schlichting, C; Shankar, V, 2014)	0.4
"Blood samples (2-4 per child) were collected from 13 children ages 9 months to 6 years admitted to the pediatric intensive care unit who were receiving standard piperacillin/tazobactam dosing regimens to treat infections."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill young children. Cies, JJ; Kuti, JL; Schlichting, C; Shankar, V, 2014)	0.4
" The only dosing regimens that achieved optimal PTA at the Clinical Laboratory Standards Institute susceptibility breakpoint of 16 μg/mL against Psuedomonas aeruginosa were 100 mg/kg every 6 hours administered as a 3-hour prolonged infusion and 400 mg/kg administered as a 24-hour continuous infusion."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill young children. Cies, JJ; Kuti, JL; Schlichting, C; Shankar, V, 2014)	0.4
" The probability of target attainment (PTA) of maintaining free piperacillin levels above the MIC during the entire dosing interval was estimated by simulation of intermittent and continuous infusions."	( Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis. Asín-Prieto, E; Isla, A; Maynar, J; Rodríguez-Gascón, A; Sánchez-Izquierdo, JÁ; Soraluce, A; Trocóniz, IF, 2014)	0.4
" Based on the pharmacokinetic/pharmacodynamic analysis, dosing recommendations are given considering the residual renal function of the patient and the MIC for the isolated bacteria."	( Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis. Asín-Prieto, E; Isla, A; Maynar, J; Rodríguez-Gascón, A; Sánchez-Izquierdo, JÁ; Soraluce, A; Trocóniz, IF, 2014)	0.4
" Bacterial killing following administration of piperacillin via bolus dosing and that after extended infusions were similar."	( Impact of Bolus dosing versus continuous infusion of Piperacillin and Tazobactam on the development of antimicrobial resistance in Pseudomonas aeruginosa. Felton, TW; Goodwin, J; Gregson, L; Hope, WW; Howard, SJ; Livermore, J; Neely, MN; O'Connor, L; Sharp, A, 2013)	0.39
" In treatment group, the percentage of duration of blood drug level higher than MIC account for dosing interval (%T>MIC) was 86."	( [Treatment study of hospital acquired pneumonia by optimizing dosing regimen of piperacillin/tazobactam:prolonged vs. regular infusion]. Dong, WL; Lü, Y; Wang, DH; Xia, R; Yan, Z; Yang, Y, 2013)	0.39
"TZP prolonged the infusion time dosing regimens using in Gram negative bacteria induced by high MIC value of HAP have more stable plasma concentration, curative clinical effect and reduce the cost of treatment."	( [Treatment study of hospital acquired pneumonia by optimizing dosing regimen of piperacillin/tazobactam:prolonged vs. regular infusion]. Dong, WL; Lü, Y; Wang, DH; Xia, R; Yan, Z; Yang, Y, 2013)	0.39
" The percentage of the dosing interval that tazobactam concentrations remained above a threshold (%Time>threshold) was identified as the PK-PD exposure measure that was most closely associated with efficacy."	( Pharmacological basis of β-lactamase inhibitor therapeutics: tazobactam in combination with Ceftolozane. Ambrose, PG; Bhavnani, SM; Bulik, CC; Forrest, A; Friedrich, LV; Jones, RN; McCauley, J; Mendes, RE; Okusanya, OO; Steenbergen, JN; Vanscoy, B, 2013)	0.39
" The dosage of TAZ/PIPC was 95."	( [Concentration of tazobactam/piperacillin in the cerebrospinal fluid of patients with Haemophilus influenzae type B meningitis]. Fukasawa, C; Hoshino, T; Ishiwada, N; Kutsuna, S; Sato, H; Sawada, K, 2013)	0.39
" The predefined PK/pharmacodynamic (PK/PD) target was 100% fT>4MIC [percentage of time during a dosing interval that the free (f) drug concentration exceeded 4 times the MIC]."	( Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial. Boelens, J; Carlier, M; Carrette, S; Claeys, G; De Waele, JJ; Decruyenaere, J; Depuydt, P; Hoste, E; Leroux-Roels, I; Stove, V; Verstraete, AG, 2014)	0.4
"5g piperacillin/tazobactam administered evry 8h resulted in piperacillin concentrations in plasma and ISF >32mg/L throughout most of the dosing interval."	( Pharmacokinetics of piperacillin and tazobactam in plasma and subcutaneous interstitial fluid in critically ill patients receiving continuous venovenous haemodiafiltration. Boots, RJ; Jarrett, P; Kirkpatrick, CM; Lipman, J; Roberts, JA; Varghese, JM, 2014)	0.4
" Target attainment rates for the time unbound piperacillin concentrations remained above the MIC for 50% and 75% of the dosing interval at steady state were evaluated."	( Developmental pharmacokinetics of piperacillin and tazobactam using plasma and dried blood spots from infants. Benjamin, DK; Bloom, BT; Capparelli, EV; Castro, L; Cohen-Wolkowiez, M; Gao, J; Poindexter, B; Smith, PB; Watt, KM; Zhou, C, 2014)	0.4
"Recent evidence suggests that current antimicrobial dosing may be inadequate for some critically ill patients."	( Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. Akers, KS; Cannon, JW; Chung, KK; Cota, JM; Murray, CK; Niece, KL, 2014)	0.4
" Alternative dosing strategies were explored in silico."	( Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. Akers, KS; Cannon, JW; Chung, KK; Cota, JM; Murray, CK; Niece, KL, 2014)	0.4
" Monte Carlo pharmacokinetic simulations demonstrated increased time at therapeutic drug levels with extended infusion dosing at a drug cost savings of up to 66."	( Modified Augmented Renal Clearance score predicts rapid piperacillin and tazobactam clearance in critically ill surgery and trauma patients. Akers, KS; Cannon, JW; Chung, KK; Cota, JM; Murray, CK; Niece, KL, 2014)	0.4
" By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets."	( Individualization of piperacillin dosing for critically ill patients: dosing software to optimize antimicrobial therapy. Boselli, E; Felton, TW; Hope, WW; Lodise, TP; Neely, MN; Roberts, JA; Van Guilder, M, 2014)	0.4
" Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals."	( Extended-Infusion versus standard-infusion piperacillin-tazobactam for sepsis syndromes at a tertiary medical center. Ahuja, T; Chen, D; Chen, XJ; Cutro, SR; Dubrovskaya, Y; Holzman, R; Mehta, SA; Papadopoulos, J; Phillips, MS; Scipione, MR, 2014)	0.4
" The experiment duration was 10 days, and the ceftolozane-tazobactam dose ratio (2:1) and dosing interval (every 8 h) were selected to approximate those expected to be used clinically."	( Relationship between ceftolozane-tazobactam exposure and selection for Pseudomonas aeruginosa resistance in a hollow-fiber infection model. Ambrose, PG; Bhavnani, SM; Castanheira, M; Friedrich, LV; Jones, RN; McCauley, J; Mendes, RE; Steenbergen, JN; VanScoy, BD, 2014)	0.4
" A 5,000 patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for multiple dosing regimens, using 50% of free drug time above the minimum inhibitory concentration (MIC) as the primary pharmacodynamic threshold."	( Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia. Cies, JJ; Jain, J; Kuti, JL, 2015)	0.42
"In children with fever and neutropenia, piperacillin/tazobactam dosing regimens that are administered every 4 hr or that employ prolonged or continuous infusions should be considered to optimize pharmacodynamic exposure."	( Population pharmacokinetics of the piperacillin component of piperacillin/tazobactam in pediatric oncology patients with fever and neutropenia. Cies, JJ; Jain, J; Kuti, JL, 2015)	0.42
" Drug concentrations were considered adequate if they remained 4-8× the clinical MIC breakpoint for Pseudomonas aeruginosa for 50% (TZP) or 40% (MEM) of the dosing interval."	( β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study. Antonucci, E; Beumier, M; Cristallini, S; de Backer, D; Donadello, K; Jacobs, F; Roberts, JA; Rondelet, B; Scolletta, S; Taccone, FS; Vincent, JL, 2015)	0.42
"A better dosing strategy can improve clinical outcomes for patients."	( Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. Chen, L; Wang, Y; Yang, H; Zhang, C; Zhou, Q, 2015)	0.42
"22) between the two dosing regimens."	( Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. Chen, L; Wang, Y; Yang, H; Zhang, C; Zhou, Q, 2015)	0.42
" Therefore, this dosing strategy could be considered in clinical practice."	( Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. Chen, L; Wang, Y; Yang, H; Zhang, C; Zhou, Q, 2015)	0.42
" 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."	( New antibiotic dosing in infants. Pineda, LC; Watt, KM, 2015)	0.42
" Population pharmacokinetic parameters were estimated using NONMEM, and Monte Carlo simulations were performed for three 4-hour dosing regimens to calculate probability of target attainment (PTA) at ≥50% fT>MIC."	( Population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients. Cheatham, SC; Chung, EK; Fleming, MR; Healy, DP; Kays, MB; Shea, KM, 2015)	0.42
"The study was to establish a population pharmacokinetic (PPK) model of piperacillin (PIP) and tazobactam (TAZ) that explain pharmacokinetic variability and to propose optimized dosage regimens in patients with nosocomial infections."	( Population Pharmacokinetics and Pharmacodynamics of Piperacillin/Tazobactam in Patients with Nosocomial Infections. Chen, R; Qian, CY; Qian, Q; Sun, MR; Wang, LY; Wang, ML; Zou, SL, 2016)	0.43
"In total, 310 PIP and 280 TAZ concentration-time points were collected at steady state over multiple dosing intervals from 50 patients who received PIP/TAZ infused within 30 min or over 3 h."	( Population Pharmacokinetics and Pharmacodynamics of Piperacillin/Tazobactam in Patients with Nosocomial Infections. Chen, R; Qian, CY; Qian, Q; Sun, MR; Wang, LY; Wang, ML; Zou, SL, 2016)	0.43
" TDM provides useful feedback of dosing adequacy to guide dose optimization."	( Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial. Gardner, JH; Hahn, U; Lehman, S; Peake, SL; Roberts, JA; Roberts, MS; Sime, FB; Tiong, IS; Warner, MS, 2015)	0.42
"Blood samples were collected every hour over an 8-hour dosing interval."	( Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy. Amyot, J; Awissi, DK; Beauchamp, A; Fagnan, M; Hébert, E; Lavallée, C; Lavigne, V; Leblanc, M; Lebrun, G; Munoz, DL; Pichette, V; Robitaille, R; Savoie, M; Tétreault, N; Varin, F, 2015)	0.42
"The primary outcome was the proportion of patients who achieved an unbound piperacillin plasma concentration above a target minimum inhibitory concentration (MIC) of 64 mg/L (MIC that inhibits 90% of isolates for Pseudomonas aeruginosa) for at least 50% of the dosing interval; 18 (90%) of the 20 patients achieved this outcome."	( Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy. Amyot, J; Awissi, DK; Beauchamp, A; Fagnan, M; Hébert, E; Lavallée, C; Lavigne, V; Leblanc, M; Lebrun, G; Munoz, DL; Pichette, V; Robitaille, R; Savoie, M; Tétreault, N; Varin, F, 2015)	0.42
" A population pharmacokinetic (PK) model with the plasma-to-epithelial lining fluid (ELF) kinetics of ceftolozane/tazobactam was used to justify dosing regimens for patients with nosocomial pneumonia in phase 3 studies."	( Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia. Huntington, JA; Miller, BW; Nicolau, DP; Xiao, AJ, 2016)	0.43
" Similar to other cephalosporins, the best pharmacodynamic property to predict efficacy for ceftolozane/tazobactam is a concentration that remains above the minimum inhibitory concentration (MIC) for 40-50% of the dosing interval."	( Ceftolozane/Tazobactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination. Cho, JC; Estrada, SJ; Fiorenza, MA, 2015)	0.42
"We sought to describe a case of pharmacodynamically-optimized dosing of piperacillin-tazobactam in a patient that cleared their infections after treatment with high-dose, extended-infusion piperacillin-tazobactam and summarize the literature on the benefits of extended-infusion of beta-lactams."	( Microbiologic clearance following transition from standard infusion piperacillin-tazobactam to extended-infusion for persistent Gram-negative bacteremia and possible endocarditis: A case report and review of the literature. D'Agostino, C; Rhodes, NJ; Roberts, JA; Scheetz, MH; Skoglund, E, 2015)	0.42
"We present the first case to our knowledge that describes failure to respond and subsequent response within a single patient where beta-lactam dosing was altered to optimize pharmacokinetics and pharmacodynamics (PK-PD)."	( Microbiologic clearance following transition from standard infusion piperacillin-tazobactam to extended-infusion for persistent Gram-negative bacteremia and possible endocarditis: A case report and review of the literature. D'Agostino, C; Rhodes, NJ; Roberts, JA; Scheetz, MH; Skoglund, E, 2015)	0.42
" Piperacillin concentrations were determined at various points within the MARS circuit, and patient serum concentrations were reported throughout the dosing interval while receiving MARS therapy."	( Extracorporeal Elimination of Piperacillin/Tazobactam during Molecular Adsorbent Recirculating System Therapy. El-Zoghby, ZM; Frazee, EN; Larson, SL; Nyberg, SL; Personett, HA, 2015)	0.42
"Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population."	( Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations? Brock, B; Gjedsted, J; Hardlei, TF; Juul, RV; Kreilgaard, M; Öbrink-Hansen, K; Storgaard, M; Thomsen, MK, 2015)	0.42
"We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies."	( Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DA Abdul-Aziz, MH; Akova, M; Bassetti, M; De Waele, JJ; Dimopoulos, G; Dulhunty, J; Kaukonen, KM; Koulenti, D; Lipman, J; Martin, C; Montravers, P; Rello, J; Rhodes, A; Roberts, JA; Starr, T; Wallis, SC, 2016)	0.43
" Additionally, in patients with a SOFA score of ≥9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73."	( Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DA Abdul-Aziz, MH; Akova, M; Bassetti, M; De Waele, JJ; Dimopoulos, G; Dulhunty, J; Kaukonen, KM; Koulenti, D; Lipman, J; Martin, C; Montravers, P; Rello, J; Rhodes, A; Roberts, JA; Starr, T; Wallis, SC, 2016)	0.43
" The PK/PD target attainment (100%fT>MIC) was defined as free (f) piperacillin plasma concentrations that remain, during the entire dosing interval (T), above the minimum inhibitory concentration (100%fT>MIC) within days 4-8 (when CFB culminates and disappears)."	( A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam. Bezouška, J; Havel, E; Kaška, M; Malbrain, ML; Martínková, J; Šafránek, P, 2016)	0.43
" Its dosing and chemistry provide expansive antimicrobial coverage of gram-negative organisms, including Pseudomonas aeruginosa, and stable activity against many β-lactamases, as well as coverage of most extended-spectrum β-lactamase-producing organisms and some anaerobes."	( Ceftolozane-tazobactam: A new-generation cephalosporin. Cluck, D; Lewis, P; Moorman, J; Spivey, J; Stayer, B, 2015)	0.42
" Drug dosing was similar in the two groups."	( Serum β-lactam concentrations in critically ill patients with cirrhosis: a matched case-control study. Cotton, F; Creteur, J; Gustot, T; Hites, M; Jacobs, F; Lheureux, O; Surin, R; Taccone, FS; Trepo, E; Vincent, JL; Wolff, F, 2016)	0.43
"57 μg/ml, concentration at the end of the dosing interval (Cmin) of 31."	( Ceftolozane-Tazobactam Pharmacokinetics in a Critically Ill Patient on Continuous Venovenous Hemofiltration. Gonzales, JP; Heil, EL; Mehrotra, S; Nicolau, DP; Oliver, WD; Robinett, K; Saleeb, P, 2015)	0.42
"We have previously demonstrated the pharmacokinetic-pharmacodynamic (PK-PD) index best associated with the efficacy of tazobactam when used in combination with ceftolozane to be the percentage of the dosing interval during which tazobactam concentrations remained above a threshold value (%time>threshold)."	( Pharmacokinetics-Pharmacodynamics of Tazobactam in Combination with Piperacillin in an In Vitro Infection Model. Ambrose, PG; Bhavnani, SM; Bulik, CC; Castanheira, M; Forrest, A; Friedrich, LV; Jones, RN; Mendes, RE; Nicasio, AM; Okusanya, OO; Steenbergen, JN; VanScoy, BD, 2016)	0.43
"The compatibility of vancomycin and piperacillin-tazobactam in concentrations typically used in extended-infusion dosing schemes was evaluated."	( Visual and absorbance analyses of admixtures containing vancomycin and piperacillin-tazobactam at commonly used concentrations. Manek, M; O'Donnell, JN; Rhodes, NJ; Scheetz, MH; Venkatesan, N, 2016)	0.43
"This multicentre study aimed to describe the pharmacokinetics (PK) of piperacillin in critically ill patients with multiple organ dysfunction syndrome (MODS) receiving continuous venovenous haemodiafiltration (CVVHDF), to identify the sources of PK variability and evaluate different dosing regimens to develop recommendations based on clinical parameters."	( Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: effect of type of dialysis membrane on dosing requirements. Calvo, G; Fernández, J; Llauradó-Serra, M; Martín-Loeches, I; Pontes, C; Rodríguez, A; Soy, D; Torres, A; Ulldemolins, M; Vaquer, S, 2016)	0.43
" Therapeutic drug monitoring can be used to guide dosing so as to maximise therapeutic effect whilst reducing the likelihood of exposure-related toxicity."	( Is high-dose β-lactam therapy associated with excessive drug toxicity in critically ill patients? Cotta, MO; Lipman, J; Little, PJ; McDonald, C; McWhinney, B; Roberts, JA; Ungerer, JP, 2016)	0.43
" After only 24 hours of treatment in the neutropenic murine thigh infection model, the generic amplified the resistant subpopulation up to 20-times compared with the innovator, following an inverted-U dose-response relationship."	( Impact on Bacterial Resistance of Therapeutically Nonequivalent Generics: The Case of Piperacillin-Tazobactam. Agudelo, M; Aguilar, YA; Rodriguez, CA; Vesga, O; Zuluaga, AF, 2016)	0.43
" Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μg/ml for >50% of the dosing cycle."	( Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT. Aduroja, OA; Amde, M; Connor, MJ; Fissell, WH; Gould, ER; Groszek, JJ; Madonia, PN; Nesbitt, R; Salem, C; Shotwell, MS; Taylor, ME; Tolwani, AJ; Wei, P, 2016)	0.43
"The purpose of this study is to evaluate the outcome differences between patients receiving piperacillin-tazobactam pre- and post-implementation of an extended infusion dosing protocol in a community teaching hospital adult intensive care unit."	( Outcomes of an extended-infusion piperacillin-tazobactam protocol implementation in a community teaching hospital adult intensive care unit. Bergman, SJ; Metzke, ME; Pointer, S; Schmees, PM; Strader, BD; Valenti, KM, 2016)	0.43
"On December 19th, 2011, extended infusion dosing of piperacillin-tazobactam was implemented at St."	( Outcomes of an extended-infusion piperacillin-tazobactam protocol implementation in a community teaching hospital adult intensive care unit. Bergman, SJ; Metzke, ME; Pointer, S; Schmees, PM; Strader, BD; Valenti, KM, 2016)	0.43
"Two multivariate chemometric models, namely, partial least-squares regression (PLSR) and linear support vector regression (SVR), are presented for the analysis of amoxicillin trihydrate and dicloxacillin sodium in the presence of their common impurity (6-aminopenicillanic acid) in raw materials and in pharmaceutical dosage form via handling UV spectral data and making a modest comparison between the two models, highlighting the advantages and limitations of each."	( Partial Least-Squares and Linear Support Vector Regression Chemometric Methods for Simultaneous Determination of Amoxicillin Trihydrate and Dicloxacillin Sodium in the Presence of Their Common Impurity. Abdelaleem, EA; Hussein, EA; Naguib, IA; Zaazaa, HE, 2016)	0.61
"Introduction To enhance the probability of pharmacodynamic target attainment, piperacillin-tazobactam can be administered as either a continuous or extended-infusion dosage regimen for the treatment of gram-negative infections."	( Evaluation of an alternative extended-infusion piperacillin-tazobactam dosing strategy for the treatment of gram-negative infections. Hickson, RP; Judd, WR; Mueller, JE; Ratliff, PD; Winstead, EM, 2016)	0.43
"A better dosing strategy can improve clinical outcomes for patients."	( Evaluation Outcomes Associated with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Systematic Review and Meta-Analysis. Cui, X; Liu, L; Ma, Z; Yang, H, )	0.13
" In order to determine the appropriate dosing regimen and to provide a rationale for the development of dosing guidelines suitable for this population, further popPK studies of piperacillin/tazobactam would need to be conducted."	( Target attainment analysis and optimal sampling designs for population pharmacokinetic study on piperacillin/tazobactam in neonates and young infants. Chen, C; Chen, Y; Dong, M; Li, Q; Li, Z; Lu, J; Wu, D; Zhu, Y, 2016)	0.43
"Pharmacodynamic profiling of piperacillin using Monte Carlo simulation was performed to explore the target attainment probability of different dosing regimens for infections caused by different isolated pathogens."	( Target attainment analysis and optimal sampling designs for population pharmacokinetic study on piperacillin/tazobactam in neonates and young infants. Chen, C; Chen, Y; Dong, M; Li, Q; Li, Z; Lu, J; Wu, D; Zhu, Y, 2016)	0.43
"The dosing regimen and sampling schedules proposed in this study should be evaluated in future popPK studies of piperacillin/tazobactam in neonates and infants."	( Target attainment analysis and optimal sampling designs for population pharmacokinetic study on piperacillin/tazobactam in neonates and young infants. Chen, C; Chen, Y; Dong, M; Li, Q; Li, Z; Lu, J; Wu, D; Zhu, Y, 2016)	0.43
"Controversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta-lactam antibiotics."	( Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients. Eliasson, E; Giske, CG; Petersson, J, 2016)	0.43
" Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2-3 days when feasible."	( Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients. Eliasson, E; Giske, CG; Petersson, J, 2016)	0.43
" Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27."	( Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients. Eliasson, E; Giske, CG; Petersson, J, 2016)	0.43
" The percentage of the dosing interval for which the free piperacillin concentration (%fT) exceeds the minimum inhibitory concentration (MIC) was calculated."	( Clinical outcomes of extended versus intermittent administration of piperacillin/tazobactam for the treatment of hospital-acquired pneumonia: a randomized controlled trial. Bao, H; Lv, Y; Wang, D; Xue, J; Yan, Z, 2017)	0.46
"To determine ceftolozane/tazobactam transmembrane clearances (CLTM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT)."	( Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy. Chaijamorn, W; Lewis, SJ; Mueller, BA; Shaw, AR, 2017)	0.46
" Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT."	( Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy. Chaijamorn, W; Lewis, SJ; Mueller, BA; Shaw, AR, 2017)	0.46
" We performed 5,000 Monte Carlo simulations for various dosing regimens and minimal inhibitory concentration and calculated the probability to spend 100% of the time over 64 mg/L."	( Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and the Risk of Under- and Overdosing. Breilh, D; Jaber, S; Jean-Pierre, H; Jung, B; Legeron, R; Mahul, M; Molinari, N; Signe, J; Uhlemann, AC, 2017)	0.46
"Using a conventional dosing of 16 g/2 g/24 hr continuous infusion, obese patients were more likely than nonobese patients to experience piperacillin underdosing when facing high minimal inhibitory concentration pathogens."	( Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and the Risk of Under- and Overdosing. Breilh, D; Jaber, S; Jean-Pierre, H; Jung, B; Legeron, R; Mahul, M; Molinari, N; Signe, J; Uhlemann, AC, 2017)	0.46
"To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen."	( Dose optimization of piperacillin/tazobactam in critically ill children. Carlier, M; De Cock, PAJG; de Jaeger, A; De Paepe, P; Delanghe, JR; Della Pasqua, OE; Robays, H; van Dijkman, SC; Vande Walle, J; Verstraete, AG; Willems, J, 2017)	0.46
"Standard intermittent dosing regimens do not ensure optimal piperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure."	( Dose optimization of piperacillin/tazobactam in critically ill children. Carlier, M; De Cock, PAJG; de Jaeger, A; De Paepe, P; Delanghe, JR; Della Pasqua, OE; Robays, H; van Dijkman, SC; Vande Walle, J; Verstraete, AG; Willems, J, 2017)	0.46
"Optimal dosing of β-lactam antibiotics in critically ill patients is a challenge given the unpredictable pharmacokinetic profile of this patient population."	( Target attainment with continuous dosing of piperacillin/tazobactam in critical illness: a prospective observational study. Aardema, H; Alffenaar, JW; Dieperink, W; Kosterink, JGW; Nannan Panday, P; van Hateren, K; Wessels, M; Zijlstra, JG, 2017)	0.46
" It is assumed that PIP-plasma concentrations above the clinical breakpoint of the target pathogen [Pseudomonas aeruginosa, clinical breakpoint at minimal inhibitory concentration (MIC) 16 mg/L] should be reached for 100% of the dosing interval or >4xMIC (64 mg/L) for 50% of the dosing interval."	( Measurement of piperacillin plasma concentrations in cancer patients with suspected infection. Bremer-Streck, S; Hochhaus, A; Kiehntopf, M; Lindig, U; Rachow, T; Schlattmann, P; Schlüter, V; Scholl, S; von Lilienfeld-Toal, M, 2017)	0.46
" Other options such as ertapenem and moxifloxacin may be reasonable where multiple daily dosing or intravenous administration is inappropriate."	( Clinical efficacy of piperacillin/tazobactam in the treatment of complicated skin and soft tissue infections. Hayashi, Y; Katayama, M; Suzuki, D; Takimoto, K; Wang, Q, 2017)	0.46
" A pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug concentrations was conducted to simulate dosing regimens needed to attain the pharmacodynamic target in abdominal sites."	( Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and peritoneum of surgery patients, and dosing considerations based on site-specific pharmacodynamic target attainment. Ikawa, K; Kajihara, T; Morikawa, N; Murakami, Y; Murao, N; Ohge, H; Shigemoto, N; Shimada, N; Sueda, T; Uegami, S; Uemura, K; Watadani, Y; Yano, R, 2017)	0.46
"Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels."	( Dosing antibiotics in neonates: review of the pharmacokinetic data. Cohen-Wolkowiez, M; Greenberg, RG; Rivera-Chaparro, ND, 2017)	0.46
"Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis."	( Antibiotic Dosing in Continuous Renal Replacement Therapy. Mueller, BA; Shaw, AR, 2017)	0.46
" We examined the effect of these different dosing regimens on renal function."	( Frequency of Acute Kidney Injury Caused by Tazobactam/Piperacillin in Patients with Pneumonia and Chronic Kidney Disease: A Retrospective Observational Study. Morimoto, T; Morimoto, Y; Nagashima, H; Tokuyama, S, 2017)	0.46
" There are currently no pediatric dosing recommendations."	( Dose-Exposure Simulation for Piperacillin-Tazobactam Dosing Strategies in Infants and Young Children. Autmizguine, J; Kassir, N; Litalien, C; Théorêt, Y; Thibault, C; Varin, F, 2017)	0.46
"To determine appropriate TZP dosing strategies in children 2 months - 6 years according to age and different minimal inhibitory concentrations (MICs)."	( Dose-Exposure Simulation for Piperacillin-Tazobactam Dosing Strategies in Infants and Young Children. Autmizguine, J; Kassir, N; Litalien, C; Théorêt, Y; Thibault, C; Varin, F, 2017)	0.46
" Dosing of piperacillin-tazobactam requires an understanding of this patient group to maximise the effectiveness of this antibiotic and limit a further emergence of resistant pathogens."	( A UHPLC-MS/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent. Guerra Valero, YC; Lipman, J; Naicker, S; Ordenez Meija, JL; Parker, SL; Roberts, JA; Wallis, SC, 2018)	0.48
"We sought to identify ceftolozane/tazobactam dosing schemes that optimized the probability of target attainment (PTA) against infections due to MDR-PA with ceftolozane/tazobactam MICs between 4 and 32 mg/L across different categories of renal function."	( Determination of alternative ceftolozane/tazobactam dosing regimens for patients with infections due to Pseudomonas aeruginosa with MIC values between 4 and 32 mg/L. Lodise, TP; Natesan, S; Pai, MP, 2017)	0.46
"Extended infusion ceftolozane/tazobactam regimens should be investigated as a potential dosing solution to improve the PTA against infections due to MDR-PA with higher ceftolozane/tazobactam MICs."	( Determination of alternative ceftolozane/tazobactam dosing regimens for patients with infections due to Pseudomonas aeruginosa with MIC values between 4 and 32 mg/L. Lodise, TP; Natesan, S; Pai, MP, 2017)	0.46
"375 g dosing regimens."	( Simplifying Piperacillin/Tazobactam Dosing: Pharmacodynamics of Utilizing Only 4.5 or 3.375 g Doses for Patients With Normal and Impaired Renal Function. Grupper, M; Kuti, JL; Nicolau, DP; Thabit, AK, 2017)	0.46
"In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics."	( Considerable variation of trough β-lactam concentrations in older adults hospitalized with infection-a prospective observational study. Hatti, M; Odenholt, I; Resman, F; Solomonidi, N; Tham, J, 2018)	0.48
"The aim of this study was to evaluate the effectiveness of ceftolozane/tazobactam (C/T) for treating extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) infections, and to analyze whether high C/T dosing (2 g ceftolozane and 1 g tazobactam every 8 h) and infection source control have an impact on outcome."	( Ceftolozane/tazobactam for the treatment of XDR Pseudomonas aeruginosa infections. Almirante, B; Arévalo, Á; Campany, D; Escolà-Vergé, L; Ferrer, R; Larrosa, N; Len, O; Los-Arcos, I; Nuvials, X; Pigrau, C; Viñado, B, 2018)	0.48
" As limited data are available regarding piperacillin CNS exposure in patients without or with low-grade inflammation, a clinical study was conducted (1) to quantify CNS exposure of piperacillin by cerebral microdialysis and (2) to evaluate different dosing regimens in order to improve probability of target attainment (PTA) in brain."	( Brain Exposure to Piperacillin in Acute Hemorrhagic Stroke Patients Assessed by Cerebral Microdialysis and Population Pharmacokinetics. Arshad, U; Beer, R; Dorn, C; Fuhr, U; Helbok, R; Kofler, M; Kratzer, A; Taubert, M; Ullah, S; Zeitlinger, M, 2020)	0.56
" Six piperacillin/tazobactam dosing regimens for Kp68 (4/0."	( Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Klebsiella pneumoniae. Cottrell, K; Harris, PNA; Heffernan, AJ; Islam, K; Lipman, J; Naicker, S; Roberts, JA; Sime, FB; Sumi, CD; Wallis, SC, 2020)	0.56
"For Kp68, all simulated dosing regimens exhibited approximately 4 log10 of bacterial killing at 8 h followed by regrowth to approximately 1011 cfu/mL within 24 h."	( Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Klebsiella pneumoniae. Cottrell, K; Harris, PNA; Heffernan, AJ; Islam, K; Lipman, J; Naicker, S; Roberts, JA; Sime, FB; Sumi, CD; Wallis, SC, 2020)	0.56
"Pharmacokinetics and optimal dosing of piperacillin tazobactam (PT) have not been well studied in pediatric patients undergoing extracorporeal oxygenation membrane (ECMO)."	( [Plasmatic concentracion of piperacillin/tazobactam in pediatric patients on ECMO support. Preliminary analysis]. Izquierdo C, G; Navea M, D; Torres T, JP; Valverde G, C; Zylbersztajn, B, 2020)	0.56
" Plasmatic concentrations of piperacillin were obtained in the middle of the dosing interval using high performance liquid chromatography."	( [Plasmatic concentracion of piperacillin/tazobactam in pediatric patients on ECMO support. Preliminary analysis]. Izquierdo C, G; Navea M, D; Torres T, JP; Valverde G, C; Zylbersztajn, B, 2020)	0.56
" This review summarizes the population pharmacokinetic models developed for piperacillin-tazobactam and provides comprehensive data on current dosing strategies while identifying significant covariates in critically ill patients."	( Piperacillin-Tazobactam in Intensive Care Units: A Review of Population Pharmacokinetic Analyses. Caissy, JA; El-Haffaf, I; Marsot, A, 2021)	0.62
" However, it remains unknown whether the increased VIN risk in combination treatment with vancomycin and tazobactam/piperacillin, which is a VIN risk factor, can be diminished by AUC-guided vancomycin dosing (vancomycin-AUC)."	( Impact of Area Under the Concentration-Time Curve on the Prevalence of Vancomycin-Induced Nephrotoxicity in Combination With Tazobactam/Piperacillin or Cefepime: A Single-Institution Retrospective Study. Aizawa, F; Azuma, M; Chuma, M; Goda, M; Hamano, H; Ishizawa, K; Izumi, Y; Nakamoto, A; Okada, N; Yagi, K; Zamami, Y, 2021)	0.62
" These results strongly suggest that VIN prevention may be difficult with AUC-guided vancomycin dosing in patients receiving VT."	( Impact of Area Under the Concentration-Time Curve on the Prevalence of Vancomycin-Induced Nephrotoxicity in Combination With Tazobactam/Piperacillin or Cefepime: A Single-Institution Retrospective Study. Aizawa, F; Azuma, M; Chuma, M; Goda, M; Hamano, H; Ishizawa, K; Izumi, Y; Nakamoto, A; Okada, N; Yagi, K; Zamami, Y, 2021)	0.62
" 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."	( Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial. Annecke, T; Bach, F; Bauer, M; Bracht, H; Brenner, T; Brinkmann, A; Frey, O; Hagel, S; Hohn, A; Jarczak, D; Kiehntopf, M; Kluge, S; König, C; Lehmann, T; Michels, G; Müller, C; Neugebauer, S; Nierhaus, A; Pletz, MW; Roberts, JA; Weigand, M; Weismann, D; Witzke, D, 2022)	0.72
"To explore extracorporeal membrane oxygenation (ECMO)-related alterations of the pharmacokinetics (PK) of piperacillin/tazobactam and determine an optimal dosage regimen for critically ill adult patients."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation. Kim, HI; Kim, HS; Kim, YK; Lee, DH; Lee, SH; Park, S, 2022)	0.72
" The percentage of time within 24 h for which the free concentration exceeded the MIC at a steady-state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function were explored using Monte-Carlo simulation."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation. Kim, HI; Kim, HS; Kim, YK; Lee, DH; Lee, SH; Park, S, 2022)	0.72
" Patients with Escherichia coli or Klebsiella pneumoniae infection, but not those with Pseudomonas aeruginosa infection, exhibited a PK/pharmacodynamic target attainment >90% when the target is 50%fT>MIC, as a result of applying the currently recommended dosage regimen."	( Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation. Kim, HI; Kim, HS; Kim, YK; Lee, DH; Lee, SH; Park, S, 2022)	0.72
"Timely and appropriate dosing of antibiotics is essential for the treatment of bacterial sepsis."	( Pharmacokinetics of piperacillin and tazobactam in critically Ill patients treated with continuous kidney replacement therapy: A mini-review and population pharmacokinetic analysis. Akers, KS; Chung, KK; DeLuca, JP; Livezey, JR; Nadeau, RJ; Por, ED; Pruskowski, KA; Selig, DJ, 2022)	0.72
" However, some critically ill CKRT populations may need higher or lower doses and dosing strategies should be tailored to individuals based on all available clinical data including the specific critical care setting."	( Pharmacokinetics of piperacillin and tazobactam in critically Ill patients treated with continuous kidney replacement therapy: A mini-review and population pharmacokinetic analysis. Akers, KS; Chung, KK; DeLuca, JP; Livezey, JR; Nadeau, RJ; Por, ED; Pruskowski, KA; Selig, DJ, 2022)	0.72
"To compare the bacterial killing and emergence of resistance of intermittent versus prolonged (extended and continuous infusions) infusion dosing regimens of piperacillin/tazobactam against two Escherichia coli clinical isolates in a dynamic hollow-fibre infection model (HFIM)."	( Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Escherichia coli clinical isolates. Cottrell, K; Harris, PNA; Heffernan, AJ; Lipman, J; Naicker, S; Roberts, JA; Sime, FB; Sumi, CD; Wallis, SC, 2022)	0.72
"Three piperacillin/tazobactam dosing regimens (4/0."	( Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Escherichia coli clinical isolates. Cottrell, K; Harris, PNA; Heffernan, AJ; Lipman, J; Naicker, S; Roberts, JA; Sime, FB; Sumi, CD; Wallis, SC, 2022)	0.72
"All simulated dosing regimens against Ec44 exhibited 4 log10 of bacterial killing over 8 h without regrowth and resistance emergence throughout the experiment."	( Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Escherichia coli clinical isolates. Cottrell, K; Harris, PNA; Heffernan, AJ; Lipman, J; Naicker, S; Roberts, JA; Sime, FB; Sumi, CD; Wallis, SC, 2022)	0.72
" These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam."	( Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury. Caldwell, JT; Dong, S; Fei, L; Goldstein, SL; Hasson, D; Kaplan, J; Slagle, C; Tang Girdwood, S; Tang, P; Vinks, AA, 2023)	0.91
" A 5000-patient Monte Carlo simulation was performed using various piperacillin/tazobactam dosing regimens to determine the probability of target attainment (PTA) for 50% free time above the MIC."	( Piperacillin/Tazobactam Dose Optimization in the Setting of Piperacillin/Tazobactam-susceptible, Carbapenem-resistant Pseudomonas aeruginosa: Time to Reconsider Susceptible Dose Dependent. Gill, CM; Nicolau, DP, 2023)	0.91
" Using an opportunistic study design, we evaluated the pharmacokinetics of piperacillin/tazobactam as a probe drug to evaluate changes in antibacterial drug exposure and dosing requirements, including in older adults."	( Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan. An, G; Balevic, SJ; Chan, AW; Cohen-Wolkowiez, M; Conrad, T; Gu, K; Hemmersbach-Miller, M; Kirkpatrick, CMJ; Landersdorfer, CB; Schmader, KE; Swamy, GK; Walter, EB; Winokur, PL, 2023)	0.91
" However, for a target of 50% fT + minimum inhibitory concentration, dosing based on renal function is generally preferable to dosing by age, and simulations suggested that patients with creatinine clearance ≥ 120 mL/min may benefit from infusions of 4 g every 8 hours for organisms with higher minimum inhibitory concentrations."	( Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan. An, G; Balevic, SJ; Chan, AW; Cohen-Wolkowiez, M; Conrad, T; Gu, K; Hemmersbach-Miller, M; Kirkpatrick, CMJ; Landersdorfer, CB; Schmader, KE; Swamy, GK; Walter, EB; Winokur, PL, 2023)	0.91

Class	Description
penicillanic acids
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	796 (30.51)	18.7374
1990's	369 (14.14)	18.2507
2000's	509 (19.51)	29.6817
2010's	842 (32.27)	24.3611
2020's	93 (3.56)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	327 (11.83%)	5.53%
Reviews	157 (5.68%)	6.00%
Case Studies	318 (11.51%)	4.05%
Observational	28 (1.01%)	0.25%
Other	1,934 (69.97%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (3)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
Comparison of Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients With Ventilator Associated-pneumonia to Pseudomonas Aeruginosa in Intensive Care Units [NCT03581370]	Phase 3	80 participants (Anticipated)	Interventional	2018-09-20	Recruiting
A Phase 1, Prospective, Multi-center, Open-label Study to Assess the Plasma Pharmacokinetics and Lung Penetration of Intravenous (IV) Ceftolozane/Tazobactam in Critically Ill Patients [NCT02387372]	Phase 1	37 participants (Actual)	Interventional	2015-02-05	Completed
A Phase 1, Non-comparative, Open-label Study to Characterize the Pharmacokinetics of a Single Intravenous Dose of Ceftolozane/Tazobactam in Pediatric Patients Receiving Standard of Care Antibiotic Therapy for Proven or Suspected Gram-negative Infection or [NCT02266706]	Phase 1	43 participants (Actual)	Interventional	2014-09-17	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT02266706 (20) [back to overview]	Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Ceftolozane
NCT02266706 (20) [back to overview]	Volume of Distribution at Steady State (Vss) of Tazobactam
NCT02266706 (20) [back to overview]	Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Tazobactam
NCT02266706 (20) [back to overview]	Area Under the Plasma Concentration-Time Curve (AUClast) of Ceftolozane
NCT02266706 (20) [back to overview]	Area Under the Plasma Concentration-Time Curve (AUClast) of Tazobactam
NCT02266706 (20) [back to overview]	Elimination Half-life (t1/2) of Ceftolozane
NCT02266706 (20) [back to overview]	Elimination Half-life (t1/2) of Tazobactam
NCT02266706 (20) [back to overview]	Maximum Plasma Concentration (Cmax) of Ceftolozane
NCT02266706 (20) [back to overview]	Maximum Plasma Concentration (Cmax) of Tazobactam
NCT02266706 (20) [back to overview]	Number of Participants Who Discontinued the Study Due to an Adverse Event
NCT02266706 (20) [back to overview]	Number of Participants With One or More Adverse Events
NCT02266706 (20) [back to overview]	Plasma Clearance (CL) of Ceftolozane
NCT02266706 (20) [back to overview]	Plasma Clearance (CL) of Tazobactam
NCT02266706 (20) [back to overview]	Plasma Concentration at the Last Quantifiable Concentration (Clast) of Ceftolozane
NCT02266706 (20) [back to overview]	Plasma Concentration at the Last Quantifiable Concentration (Clast) of Tazobactam
NCT02266706 (20) [back to overview]	Time of Last Sampling Point (Tlast) of Ceftolozane
NCT02266706 (20) [back to overview]	Time of Last Sampling Point (Tlast) of Tazobactam
NCT02266706 (20) [back to overview]	Time to Maximum Plasma Concentration (Tmax) of Ceftolozane
NCT02266706 (20) [back to overview]	Time to Maximum Plasma Concentration (Tmax) of Tazobactam
NCT02266706 (20) [back to overview]	Volume of Distribution at Steady State (Vss) of Ceftolozane
NCT02387372 (20) [back to overview]	AUC0-last of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	CL of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	Clast of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	Cmax of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	Number of Participants With Adverse Events (AEs)
NCT02387372 (20) [back to overview]	T1/2 of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	Tlast of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	Tmax of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	Vss of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.
NCT02387372 (20) [back to overview]	Area Under the Concentration Time Curve (AUC) From the First to Time of the Last Dose (AUC0-last) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	AUC From the Time of the Dose to Infinity (AUC0-∞) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	Epithelial Lining Fluid (ELF) / Plasma Ratio (Intrapulmonary Penetration) of Ceftolozane and Tazobactam Concentrations in Mechanically Ventilated Participants.
NCT02387372 (20) [back to overview]	Last Quantifiable Plasma Concentration (Clast) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	Maximum Plasma Concentration (Cmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	Plasma Clearance (CL) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	Terminal Elimination Half-life (t1/2) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	Time of Last Quantifiable Plasma Concentration (Tlast)) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	Time of Maximum Plasma Concentration (Tmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	Volume of Distribution at Steady State (Vss) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.
NCT02387372 (20) [back to overview]	AUC0-∞ of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Ceftolozane

Blood was collected for the determination of AUC from time zero extrapolated to infinity of ceftolozane. AUC0-inf is expressed as geometric least squares mean and confidence interval based on back-transformed least-squares mean and confidence interval from linear mixed-effects model with group fixed effect performed on natural log-transformed values. (NCT02266706)
Timeframe: Predose and 0.5, 1, 2, 4, and 6 hours after the start of infusion for Cohorts 1 to 4 and 1, 2, and 6 hours after start of infusion for Cohorts 5 and 6.

Intervention	Hours*μg/mL (Geometric Least Squares Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	133
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	107
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	99.4
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	186
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	103
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	202
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	164
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	165
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	137

Intervention	L/kg (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	0.474
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	0.740
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	0.488
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	0.513
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	0.421
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	0.574
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.668
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	0.338
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.667

Intervention	Hours*μg/mL (Geometric Least Squares Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	17.5
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	10.2
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	17.8
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	28.9
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	14.9
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	29.9
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	24.9
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	77.6
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	22.3

Intervention	Hours*μg/mL (Geometric Least Squares Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	17.3
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	9.69
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	17.6
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	28.5
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	14.8
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	28.9
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	21.3
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	21.6
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	21.9

Intervention	Hours (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	1.45
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	1.29
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	1.34
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	1.48
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	1.30
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	1.63
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	2.21
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	3.14
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	1.73

Intervention	Hours (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	0.702
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	0.544
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	0.719
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	0.770
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	0.538
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	0.815
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	1.09
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	3.03
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.875

Intervention	μg/mL (Geometric Least Squares Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	63.5
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	56.2
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	51.4
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	96.6
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	50.5
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	91.3
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	45.0
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	34.9
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	45.2

Intervention	μg/mL (Geometric Least Squares Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	14.0
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	9.25
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	15.7
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	24.8
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	11.6
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	22.4
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	11.7
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	6.87
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	12.1

Intervention	L/hour/kg (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	0.146
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	0.168
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	0.181
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	0.162
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	0.176
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	0.149
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.118
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	0.0723
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.147

Intervention	L/hour/kg (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	0.556
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	0.886
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	0.506
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	0.519
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	0.611
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	0.502
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.385
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	0.0760
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.452

Intervention	μg/mL (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	4.01
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	2.85
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	2.47
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	5.69
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	2.53
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	5.72
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	8.70
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	10.2
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	6.26

Intervention	μg/mL (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	0.232
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	0.420
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	0.137
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	0.327
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	0.224
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	0.401
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.657
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	3.66
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.266

Intervention	Hours (Median)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	6.00
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	6.01
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	6.08
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	5.77
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	6.00
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	6.00
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	6.01
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	6.40
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	5.85

Intervention	Hours (Median)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	4.15
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	3.10
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	5.85
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	5.72
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	4.00
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	5.02
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	5.95
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	6.40
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	5.85

Intervention	Hours (Median)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	1.02
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	1.07
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	1.02
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	1.03
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	1.00
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	1.05
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	1.08
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	1.80
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	1.07

Intervention	L/kg (Geometric Mean)
Cohort 1: ≥12 to <18 Years TOL/TAZ 1000/500 mg FDC	0.274
Cohort 2: ≥7 to <12 Years TOL/TAZ 18/9 mg/kg	0.296
Cohort 3: ≥2 to <7 Years TOL/TAZ 18/9 mg/kg	0.331
Cohort 3: ≥2 to <7 Years TOL/TAZ 30/15 mg/kg	0.312
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 18/9 mg/kg	0.282
Cohort 4: ≥3 Months to <2 Years TOL/TAZ 30/15 mg/kg	0.340
Cohort 5: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.394
Cohort 6: Birth to <3 Months TOL/TAZ 12/6 mg/kg	0.344
Cohort 6: Birth to <3 Months TOL/TAZ 20/10 mg/kg	0.388

Intervention	h*ug/mL (Geometric Mean)
Critically Ill - Ceftolozane	188
Critically Ill - Tazobactam	31.0

Intervention	L/h (Geometric Mean)
Critically Ill - Ceftolozane	8.98
Critically Ill - Tazobactam	28.7

Intervention	ug/mL (Geometric Mean)
Critically Ill - Ceftolozane	5.82
Critically Ill - Tazobactam	0.357

Intervention	ug/mL (Geometric Mean)
Critically Ill - Ceftolozane	68.9
Critically Ill - Tazobactam	17.4

Intervention	Hours (Geometric Mean)
Critically Ill - Ceftolozane	2.59
Critically Ill - Tazobactam	1.47

penicillanic acid

Description

Cross-References

Synonyms (22)

Research Excerpts

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Dosage Studied

Drug Classes (1)

Research

Studies (2,609)

Market Indicators

Research Demand Index: 39.98

Study Types

Clinical Trials (3)

Trial Overview

Trial Outcomes

Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Ceftolozane

Volume of Distribution at Steady State (Vss) of Tazobactam

Area Under the Plasma Concentration-Time Curve (AUC0-inf) of Tazobactam

Area Under the Plasma Concentration-Time Curve (AUClast) of Ceftolozane

Area Under the Plasma Concentration-Time Curve (AUClast) of Tazobactam

Elimination Half-life (t1/2) of Ceftolozane

Elimination Half-life (t1/2) of Tazobactam

Maximum Plasma Concentration (Cmax) of Ceftolozane

Maximum Plasma Concentration (Cmax) of Tazobactam

Number of Participants Who Discontinued the Study Due to an Adverse Event

Number of Participants With One or More Adverse Events

Plasma Clearance (CL) of Ceftolozane

Plasma Clearance (CL) of Tazobactam

Plasma Concentration at the Last Quantifiable Concentration (Clast) of Ceftolozane

Plasma Concentration at the Last Quantifiable Concentration (Clast) of Tazobactam

Time of Last Sampling Point (Tlast) of Ceftolozane

Time of Last Sampling Point (Tlast) of Tazobactam

Time to Maximum Plasma Concentration (Tmax) of Ceftolozane

Time to Maximum Plasma Concentration (Tmax) of Tazobactam

Volume of Distribution at Steady State (Vss) of Ceftolozane

AUC0-last of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

CL of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Clast of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Cmax of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Number of Participants With Adverse Events (AEs)

T1/2 of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Tlast of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Tmax of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Vss of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Area Under the Concentration Time Curve (AUC) From the First to Time of the Last Dose (AUC0-last) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

AUC From the Time of the Dose to Infinity (AUC0-∞) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

Epithelial Lining Fluid (ELF) / Plasma Ratio (Intrapulmonary Penetration) of Ceftolozane and Tazobactam Concentrations in Mechanically Ventilated Participants.

Last Quantifiable Plasma Concentration (Clast) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

Maximum Plasma Concentration (Cmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

Plasma Clearance (CL) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

Terminal Elimination Half-life (t1/2) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

Time of Last Quantifiable Plasma Concentration (Tlast)) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

Time of Maximum Plasma Concentration (Tmax) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

Volume of Distribution at Steady State (Vss) of Ceftolozane or Tazobactam in Mechanically Ventilated Participants for the First and Last Dose of Ceftolozane/Tazobactam Treatment.

AUC0-∞ of Ceftolozane/Tazobactam in Critically Ill Participants With Augmented Renal Function.

Related Drugs (457)

Related Conditions (876)

Intervention	Hours (Median)
Critically Ill - Ceftolozane	7.95
Critically Ill - Tazobactam	7.85

Intervention	Liter (Geometric Mean)
Critically Ill - Ceftolozane	30.2
Critically Ill - Tazobactam	51.6

Intervention	h*ug/mL (Geometric Mean)
	First Dose	Last Dose
Mechanically Ventilated -Tazobactam	50.7	63.0
Mechanically Ventilated- Ceftolozane	242	390

Intervention	Ratio (Mean)
	1 Hr Post-dose	2 Hr Post-dose	4 Hr Post-dose	6 Hr Post-dose	8 Hr Post-dose
Mechanically Ventilated - Ceftolozane	0.213	0.360	1.76	1.02	0.786
Mechanically Ventilated - Tazobactam	0.234	0.471	2.34	2.59	1.06

Intervention	h*ug/mL (Geometric Mean)
Critically Ill - Ceftolozane	233
Critically Ill - Tazobactam	34.8