scholarly journals Pharmacodynamic Profiling of Antimicrobials against Gram-negative Respiratory Isolates from Canadian Hospitals

2011 ◽  
Vol 22 (4) ◽  
pp. 132-136 ◽  
Author(s):  
Rebecca A. Keel ◽  
George G. Zhanel ◽  
Sheryl Zelenitsky ◽  
David P. Nicolau
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Enterobacter Cloacae ◽  
The Other ◽  
Prolonged Infusion ◽  
Target Attainment ◽  
Dosing Regimens ◽  
Dose Dependent

The objective of this study was to assess the profile of a variety of dosing regimens for common intravenous antibiotics against contemporaryEnterobacter cloacae,Escherichia coli,Klebsiella pneumoniaeandPseudomonas aeruginosaisolates collected in Canada during 2009, using pharmacodynamic modelling techniques. Monte Carlo simulation was conducted for standard and/or prolonged infusion regimens of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, doripenem, ertapenem, meropenem and piperacillin/tazobactam. The cumulative fraction of response (CFR) was calculated using bactericidal targets for each regimen against each species. All cefepime, doripenem, ertapenem and meropenem regimens achieved optimal exposures against Enterobacteriaceae, whereas target attainment was organism and dose dependent for the other agents. These results support that the currently recommended antimicrobial dosing regimens generally attain acceptable exposures to achieve the requisite pharmacodynamic targets against the Enterobacteriaceae species; however, they fall short of obtaining optimal bactericidal exposures againstP aeruginosa.BACKGROUND: With diminishing antimicrobial potency, the choice of effective empirical therapy has become more challenging. Thus, the pharmacodynamic evaluation of potential therapies is essential to identify optimal agents, doses and administration strategies.METHODS: Monte Carlo simulation was conducted for standard and/or prolonged infusion regimens of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, doripenem, ertapenem, meropenem and piperacillin/tazobactam. Minimum inhibitory concentrations were obtained forEscherichia coli(n=64 respiratory isolates),Enterobacter cloacae(n=53),Klebsiella pneumoniae(n=75) andPseudomonas aeruginosa(n=273) throughout Canada. The cumulative fraction of response (CFR) was calculated using bactericidal targets for each regimen against each species. A CFR ≥90% was defined as optimal.RESULTS: All cefepime, doripenem, ertapenem and meropenem regimens achieved optimal exposures against Enterobacteriaceae, whereas target attainment was organism and dose dependent for the other agents. Prolonged infusion doripenem and meropenem 1 g and 2 g every 8 h, along with standard infusion doripenem and meropenem 2 g every 8 h, were the only regimens to attain optimal exposures againstP aeruginosa. Ciprofloxacin had the lowest CFR againstP aeruginosa,followed by cefepime. Among theP aeruginosaisolates collected in the intensive care unit (ICU) compared with the wards, differences of 0.5% to 10% were noted in favour of non-ICU isolates for all agents; however, marked differences (10% to 15%) in CFR were observed for ciprofloxacin in favour of ICU isolates.CONCLUSION: Standard dosing of cefepime, doripenem, ertapenem and meropenem has a high likelihood of obtaining optimal pharmacodynamic indexes against these Enterobacteriaceae. ForP aeruginosa, aggressive treatment with high-dose and/or prolonged infusion regimens are likely required to address the elevated resistance rates of respiratory isolates from Canada.

Simplifying Piperacillin/Tazobactam Dosing: Pharmacodynamics of Utilizing Only 4.5 or 3.375 g Doses for Patients With Normal and Impaired Renal Function

2016 ◽  
Vol 30 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Abrar K. Thabit ◽  
Mordechai Grupper ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Inhibitory Concentration ◽  
Prolonged Infusion ◽  
Target Attainment ◽  
Dosing Regimens ◽  
Function Range ◽  
Prescribing Information

Objectives: To evaluate the pharmacodynamic exposure of piperacillin/tazobactam across the renal function range using 4.5 or 3.375 g dosing regimens. Methods: A 5000-patient Monte Carlo simulation was conducted to determine the probability of achieving 50% free time above the minimum inhibitory concentration ( fT > MIC) for piperacillin. Proposed regimens, using solely 4.5 or 3.375 g strengths, were compared with regimens listed in piperacillin/tazobactam prescribing information over creatinine clearance (CrCl) ranges of 120 mL/min to hemodialysis. The probability of target attainment (PTA) at MICs ≤ 16 μg/mL was compared between proposed and standard regimens. Results: At CrCl 41 to 120 mL/min, prolonged infusions of 4.5 g (3 hours) and 3.375 g (4 hours) every 6 hours resulted in ≥95% PTA versus ≥76% for standard regimens (0.5 hour). At CrCl 20 to 40 mL/min, 4.5 and 3.375 g every 8 hours as prolonged infusions achieved slightly higher PTA (≥98%) versus standard regimens (≥93%). Similarly, PTA achieved with prolonged infusions of 4.5 and 3.375 g every 12 hours (≥93%) was comparable with those of standard regimens (≥91%) at CrCl 1 to 19 mL/min. In hemodialysis, 100% PTA was achieved with prolonged infusion regimens. Conclusion: Piperacillin/tazobactam regimens designed around the 4.5 or 3.375 g dose and prolonged infusions provided similar or better PTA at MICs ≤ 16 μg/mL compared with standard regimens. These observations may support the stocking and use of a single piperacillin/tazobactam strength to simplify dosing.

scholarly journals Evaluating Ciprofloxacin Dosing for Pseudomonas aeruginosa Infection by Using Clinical Outcome-Based Monte Carlo Simulations

2005 ◽  
Vol 49 (10) ◽  
pp. 4009-4014 ◽  
Author(s):  
Sheryl Zelenitsky ◽  
Robert Ariano ◽  
Godfrey Harding ◽  
Alan Forrest
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Monte Carlo ◽  
Clinical Outcome ◽  
Monte Carlo Simulations ◽  
Standard Dose ◽  
High Dose ◽  
Target Attainment ◽  
Real Patient ◽  
Dosing Regimens ◽  
Cure Rates

ABSTRACT Pseudomonas aeruginosa causes serious infections whose outcome is highly dependent on antimicrobial therapy. The goal of this study was to predict the relative efficacies of three ciprofloxacin dosing regimens for P. aeruginosa infection using clinical outcome-based Monte Carlo simulations (MCS) with “real patient” demographics, pharmacokinetics, MICs, and pharmacodynamics (PDs). Each cohort consisted of 1,000 simulated study subjects. Three ciprofloxacin dosing regimens were studied, including (i) the recommended standard dose of 400 mg given intravenously (i.v.) every 12 h (q12h), (ii) the recommended high dose of 400 mg i.v. q8h, and (iii) a novel, PD-targeted regimen to attain a ƒAUC/MIC value of >86. Probability of target attainment (PTA) and probability of cure (POC) were determined for each regimen. POC with the standard dose was at least 0.90 if pathogen MICs were ≤0.25 μg/ml but only 0.59 or 0.27 if MICs were 0.5 or 1 μg/ml, respectively. Predicted cure rates in these MIC categories were significantly higher at 0.72 and 0.40 with the high dose and 0.91 and 0.72 with the PD-targeted regimen(P < 0.0001). Analyses based on the local susceptibility profile produced PTA and POC estimates of 0.44 and 0.74 with the standard ciprofloxacin dose, 0.58 and 0.81 with the high dose, and 0.84 and 0.93 with the PD-targeted regimen, respectively. In conclusion, as demonstrated by clinical outcome-based MCSs, the highest recommended ciprofloxacin dose of 400 mg i.v. q8h should be used in the treatment of P. aeruginosa infection to improve PD target attainment and clinical cure. However, even this appears ineffective if pathogen MICs are 1 μg/ml, warranting the consideration of a lower MIC breakpoint, ≤0.5 μg/ml.

scholarly journals Colistin Dosing Regimens against Pseudomonas aeruginosa in Critically Ill Patients: An Application of Monte Carlo Simulation

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 595
Author(s):  
Van Thi Khanh Nguyen ◽  
Preecha Montakantikul ◽  
Pramote Tragulpiankit ◽  
Jantana Houngsaitong ◽  
Mohd Fazli Shuib
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Pharmacokinetic Parameters ◽  
Infection Model ◽  
Carbapenem Resistant ◽  
Dosing Regimens ◽  
Microbiological Data

Our aims are to assess various colistin dosing regimens against Pseudomonas aeruginosa (P. aeruginosa) infection in critically ill patients and to propose an appropriate regimen based on microbiological data. A Monte Carlo simulation was performed using the published colistin’s pharmacokinetic parameters of critically ill patients, the published pharmacodynamic target from a mouse thigh infection model, and the minimum inhibitory concentration (MIC) results from a Vietnamese hospital. The probability of target attainment (PTA) of 80% and cumulative fraction of response (CFR) of 90% were used to evaluate the efficacy of each regimen. Of 121 P. aeruginosa laboratory datasets, the carbapenem-resistant P. aeruginosa (CRPA) and the colistin- resistant P. aeruginosa rates were 29.8% and 0.8%, respectively. MIC50,90 were both 0.5 mg/L. The simulated results showed that at MIC of 2 mg/L, most regimens could not reach the PTA target, particularly in patients with normal renal function (Creatinine clearance (CrCl) ≥ 80 mL/min). At MIC of 0.5 mg/L and 1 mg/L, current recommendations still worked well. On the basis of these results, aside from lung infection, our study recommends three regimens against P. aeruginosa infection at MIC of 0.5 mg/L, 1 mg/L, and 2 mg/L. In conclusion, higher total daily doses and fractionated colistin dosing regimens could be the strategy for difficult-to-acquire PTA cases, while a less aggressive dose might be appropriate for empirical treatment in settings with low MIC50/90.

scholarly journals Pharmacokinetic/pharmacodynamic analysis of weight- and height-scaled tobramycin dosage regimens for patients with cystic fibrosis

2019 ◽  
Vol 74 (8) ◽  
pp. 2311-2317
Author(s):  
S S Alghanem ◽  
D J Touw ◽  
A H Thomson
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Simulated Dataset ◽  
Dosage Regimens ◽  
Pharmacodynamic Analysis ◽  
Dosing Regimens ◽  
Lower Height ◽  
Higher Doses

Abstract Objectives To determine the outcomes of weight- and height-based tobramycin dosing regimens for patients with cystic fibrosis (CF). Methods A simulated dataset of 5000 patients based on 331 patients with CF was created using NONMEM. Pharmacokinetic (PK) parameters were derived for each patient from a published model using Monte Carlo simulation. The abilities of 10 and 12 mg/kg/day and 3 and 4 mg/cm/day to achieve standard and extended Cmax (20–30 and 20–40 mg/L) and AUC0–24 (80–120 and 80–150 mg·h/L) targets were evaluated. PK/pharmacodynamic (PK/PD) indices were a Cmax/MIC ratio ≥10 and an AUC0–24/MIC ratio ≥110. For these indices and a range of MICs, cumulative fractions of response (CFRs) for Pseudomonas aeruginosa were also determined. Results More patients achieved standard Cmax and AUC0–24 targets with 3 mg/cm/day (64% and 62%, respectively) than with 10 mg/kg/day (43% and 48%, respectively). AUC0–24 estimates >120 mg·h/L were more common with weight-based dosing. With higher doses, 72% achieved high target peaks with 4 mg/cm/day and 65% with 12 mg/kg/day. For the Cmax/MIC index, the maximal MIC for the target microorganism was 2 mg/L with lower doses, 2.5 mg/L with higher doses and 0.5 mg/L for AUC0–24/MIC-based regimens. The CFR for all regimens was >90% for Cmax targets and 66% to 79% for AUC0–24 targets. Conclusions A tobramycin dose of 3 mg/cm/day rather than 10 mg/kg/day achieved similar PK/PD outcomes but dose and AUC0–24 ranges were narrower and the incidence of high AUC0–24 values was lower. Height-based doses should therefore be considered for patients with CF.

scholarly journals Pharmacodynamic Evaluation of Extending the Administration Time of Meropenem using a Monte Carlo Simulation

2005 ◽  
Vol 49 (1) ◽  
pp. 461-463 ◽  
Author(s):  
Ben M. Lomaestro ◽  
G. L. Drusano
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Target Attainment ◽  
Administration Time

ABSTRACT A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against Pseudomonas aeruginosa than either 500 mg of MEM q8h (3-h infusion) or 0.5 g of imipenem-cilastatin (I-C) q6h (1-h infusion). For other pathogens, 500 mg of MEM q8h was equivalent or superior to I-C.

Антимікробна резистентність провідних збудників інфекцій сечових шляхів у Києві (Україна)

2017 ◽  
Vol 1 (2) ◽  
pp. 48-60
Author(s):  
A.G. Salmanov ◽  
A.V. Rudenko
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Staphylococcus Epidermidis ◽  
Klebsiella Oxytoca ◽  
Enterobacter Aerogenes ◽  
Enterobacter Cloacae ◽  
Proteus Vulgaris ◽  
Providencia Rettgeri ◽  
E Coli

Мета роботи — вивчити резистентність до антибіотиків бактеріальних збудників інфекцій сечових шляхів (ІСШ), виділених у пацієнтів урологічного стаціонару в м. Києві. Матеріали і методи. Досліджено 1612 штамів бактерій, виділених із сечі хворих з ІСШ (цистит, уретрит, пієлонефрит), госпіталізованих в урологічне відділення ДУ «Інститут урології НАМН України» у м. Києві протягом 2016 р. Серед пацієнтів переважали жінки — 1201 (74,5 %). Вік хворих становив від 17 до 74 років. Для збору даних використано медичну документацію лікарні. Мікробіологічні дослідження виконано у лабораторії мікробіології ДУ «Інститут урології НАМН України». Аналізували результати культурального дослідження зразків сечі, зібраних за наявності клінічних ознак ІСШ. Дослідження клінічного матеріалу та інтерпретацію отриманих результатів проводили загальноприйнятими методами. Вивчено чутливість уропатогенів до 31 антибіотика дискодифузійним методом відповідно до рекомендацій Інституту клінічних та лабораторних стандартів США (Clinical and Laboratory Standards Institute (CLSI)). Результати та обговорення. Аналіз мікробного спектра сечі виявив домінування серед уропатогенів штамів Escherichia coli (32,0 %), Enterococcus faecalis (19,5 %), Klebsiella pneumoniae (10,9 %), Staphylococcus epidermidis (8,9 %), S. haemolyticus (6,5 %) та Pseudomonas aeruginosa (6,4 %). Частка Enterococcus faecium, Enterobacter aerogenes і Streptococcus viridans становила відповідно 2,5, 2,2 і 1,6 %, Enterobacter cloacae, Klebsiella oxytoca, Acinetobacter baumannii, Proteus vulgaris та Providencia rettgeri — менше 1,0 %. У більшості випадків (69,7 %) мікроорганізми виділено у монокультурі, у решті випадків — у мікробних асоціа- ціях. Високу резистентність до тестованих антибіотиків виявили штами E. aerogenes (45,1 %), E. cloacae (45,7 %), E. faecium (40,9 %), E. faecalis (40,7 %), E. coli (39,9 %), P. aeruginosa (34,0 %), K. pneumoniae (28,6 %). Найбільш активними до уропатогенів були іміпенем (E. coli — 87,6 %, P. aeruginosa — 75,7 %, E. cloacae — 67,3 %, E. aerogenes — 72,6 %, K. pneumoniae — 93,2 %), меропенем (E. coli — 89,1 %, P. aeruginosa — 76,7 %, K. pneumoniae — 82,6 %), лефлоцин (E. coli — 74,5 %, ентерококи — 78,7 %, P. aeruginosa — 76,7 %, E. cloacae — 73,9 %, E. aerogenes — 80,4 %, K. pneumoniae — 83,5 %), амоксицилін/клавуланат (ентерококи — 84,6 %), фурагін (ентерококи — 82,6 %), цефоперазон (K. pneumoniae — 89,2 %, P. aeruginosa — 73,8 %), цефтріаксон (K. pneumoniae — 80,1 %). Висновки. Антибіотикорезистентність збудників ІСШ — важлива терапевтична проблема. Найбільшою активністю до уропатогенів характеризуються іміпенем, меропенем, лефлоцин, амоксицилін/ клавуланат, фурагін, цефоперазон, цефтріаксон, які можна розглядати як препарат вибору для призначення стартової терапії ІСШ. Необхідно здійснювати постійний моніторинг за резистентністю до дії антибіотиків. Політику використання антибіотиків у кожному стаціонарі слід визначати залежно від локальних даних щодо резистентності до протимікробних препаратів.

THE HARDNESS SPECTRUM OF QUARK- AND GLUON-JETS PRODUCED BY DIFFERENT FLAVOR QUARKS

2008 ◽  
Vol 23 (26) ◽  
pp. 4337-4343 ◽  
Author(s):  
FENG-GE TIAN ◽  
GANG CHEN ◽  
HUI-LING WEI
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Transverse Momentum ◽  
The Other ◽  
Other Hand ◽  
Gluon Jets ◽  
Quark Jets

The hardness properties of quark- and gluon-jets produced by different flavor quarks are compared in 3-jet events of e+e- collision generated with Monte Carlo Simulation Jetset 7.4 generator at [Formula: see text]. The 3-jet events are obtained using the Durham algorithm and the quark- and gluon-jets are identified by angular-method. The average values of transverse momentum 〈pt〉, multiplicity 〈N〉 and rapidity 〈y〉 versus hardness for quark- and gluon-jets of different flavors are compared. It turns out that the distributions of 〈pt〉, 〈N〉 and 〈y〉 versus hardness of quark-jets are different to their flavors, while those of the gluon-jets are insensitive to the flavors. On the other hand, the 〈pt〉 and 〈N〉 of quark- and gluon-jets are strong positive correlated with hardness, but the 〈y〉 of those are negatively correlated with hardness.

scholarly journals Estudo etiológico da infecção do trato urinário em cães

1995 ◽  
Vol 32 (1) ◽  
pp. 31 ◽  
Author(s):  
Marcia Mery Kogika ◽  
Vera Assunta Batistini Fortunato ◽  
Elsa Masae Mamizuka ◽  
Mitika Kuribayashi Hagiwara ◽  
Maria de Fatima Borges Pavan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Proteus Mirabilis ◽  
Enterobacter Cloacae ◽  
Citrobacter Freundii ◽  
Providencia Rettgeri ◽  
Cocker Spaniel

Foram estudados 51 casos de infecção urinária, em cães, considerando-se diversos fatores, tais como: agente etiológico, localização da infecção, fatores predisponentes, sexo, idade e raça. O diagnóstico da infecção do trato urinário (ITU) foi baseado no exame bacteriológico, sendo considerado positivo quando a amostra de urina, colhida com auxílio de cateter, apresentava acima de 105 bactérias/ml. Dos animais examinados, quatro cães apresentaram infecção mista, totalizando 55 microorganismos isolados. Escherichia coli foi a mais freqüentemente isolada (35,3%), seguida de Staphylococcus sp (23,5%), Proteus mirabilis (15,7%), Streptococcus sp (13,7%), Klebsiella sp (9,8%), Pseudomonas aeruginosa (3,9%), Enterobacter cloacae (2.0%), Citrobacter freundii (2.0%) e Providencia rettgeri (2,0%). Quanto à sensibilidade dos germes isolados frente a diversos agentes antimicrobianos, a norfloxacina e a gentamicina mostraram-se eficazes no tratamento de microorganismos Gram-negativos, enquanto a cefalotina e a nitrofurantoina foram mais eficazes contra bactérias Gram-positivas. Os animais que apresentaram maior frequência de ITU pertenciam às raças Cocker Spaniel e Pastor Alemão, envolvendo mais machos do que fêmeas com predominância de pielonefrites. Embora as infecções urinárias tivessem sido observadas em todas as idades, houve um predomínio nos cães de média idade. Observou-se ainda que a urolitíase foi um fator pré-disponente ou adjacente de ITU, envolvendo germes como Staphylococcus sp. e Proteus mirabilis naqueles casos com pH urinário alcalino.

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