Impact of poor compliance with levofloxacin and moxifloxacin on respiratory tract infection antimicrobial efficacy: A pharmacokinetic/pharmacodynamic simulation study

Carral, Nerea; Lukas, John C.; Oteo, Itziar; Súárez, Eduardo Viñuela

doi:10.1016/j.ijantimicag.2014.08.011

Cited by 13 publications

(11 citation statements)

References 13 publications

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“…Levofloxacin 31% binding/69% free fraction (average across multiple values from the literature [ 19 – 22 ]).…”

Section: Methodsmentioning

confidence: 99%

“…PK/PD targets for levofloxacin and ceftaroline were identified from the literature and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, and the percentages of simulated patients reaching the targets were calculated. Levofloxacin targets related to efficacy were: f AUC/MIC > 33.7 for S. aureus and S. pneumoniae , and > 100 for H. influenzae [ 19 , 24 ]. Ceftaroline targets were f T > MIC for bacteriostasis (26.8, 35 and 48.5% for S. aureus , S. pneumoniae and H. influenzae , respectively) and for 1-log 10 colony-forming unit (CFU) reductions (30.7, 44 and 73%, respectively); f T > MIC targets associated with 2-log 10 CFU reductions were also assessed for S. aureus (34.7%) and S. pneumoniae (51%) [ 17 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A Retrospective Analysis of Probability of Target Attainment in Community-Acquired Pneumonia: Ceftaroline Fosamil Versus Comparators

Cristinacce¹,

Wright²,

Stone

et al. 2019

Infect Dis Ther

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Introduction This retrospective analysis compares the probability of target attainment (PTA) for ceftriaxone, levofloxacin and ceftaroline fosamil against Staphylococcus aureus , Streptococcus pneumoniae and Haemophilus influenzae in a representative patient population with moderate-to-severe community-acquired pneumonia (CAP). Methods Published pharmacokinetic (PK) models for levofloxacin and ceftriaxone, and an existing model for ceftaroline, were used with standard dosage regimens for simulating individual PK data with covariates representative of patients with CAP (5000 patients/drug regimen). PTA for clinically relevant pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated from steady state PK profiles for a range of minimum inhibitory concentrations (MICs). Cumulative fractions of response (CFRs) were also calculated using MIC distributions from 2012 to 2017 global surveillance data. Results Ceftaroline fosamil (600 mg q12 h) achieved > 90% PTA at all exposure targets for each pathogen at European Committee on Antimicrobial Susceptibility Testing (EUCAST)/Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints, and CFRs were > 99%. Ceftriaxone, but not levofloxacin, achieved 100% PTA and > 90% CFR against S. pneumoniae . Both levofloxacin and ceftriaxone achieved high PTA and CFR against H. influenzae . Levofloxacin achieved PTAs < 90% at EUCAST/CLSI breakpoints and ceftriaxone achieved PTAs < 90% at MICs up to 2 mg/L against S. aureus ; both agents produced generally low CFRs against S. aureus (except levofloxacin against methicillin-sensitive S. aureus ), reflecting the lack of activity of these agents against methicillin-resistant S. aureus . Conclusion Ceftaroline fosamil demonstrated higher overall PTA rates than levofloxacin and ceftriaxone, in particular against S. aureus. These results provide insight regarding the potential comparative efficacy of the described antibiotics for moderate-to-severe CAP. Funding Pfizer.

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“…Levofloxacin 31% binding/69% free fraction (average across multiple values from the literature [ 19 – 22 ]).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Retrospective Analysis of Probability of Target Attainment in Community-Acquired Pneumonia: Ceftaroline Fosamil Versus Comparators

Cristinacce¹,

Wright²,

Stone

et al. 2019

Infect Dis Ther

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“…To evaluate the performance of the macrostructure dosage form for extended release, we loaded the dosage form with two drugs: (i) carbamazepine (CAR), a drug commonly used to treat epilepsy and bipolar disorder, and (ii) moxifloxacin (MOX), an antibiotic for treating bacterial infections. Poor adherence, estimated from 50 to 70%, is the major cause of treatment failure and poorly controlled epilepsy (23,24) and bacterial infections (25). The average daily dose for both drugs is between 200 and 400 mg (26,27), requiring high-capacity macrostructures for extended drug delivery.…”

Section: In Vivo Gastric Residence and Extended Drug Releasementioning

confidence: 99%

Temperature-responsive biometamaterials for gastrointestinal applications

et al. 2019

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We hypothesized that ingested warm fluids could act as triggers for biomedical devices. We investigated heat dissipation throughout the upper gastrointestinal (GI) tract by administering warm (55°C) water to pigs and identified two zones in which thermal actuation could be applied: esophageal (actuation through warm water ingestion) and extra-esophageal (protected from ingestion of warm liquids and actuatable by endoscopically administered warm fluids). Inspired by a blooming flower, we developed a capsule-sized esophageal system that deploys using elastomeric elements and then recovers its original shape in response to thermal triggering of shape-memory nitinol springs by ingestion of warm water. Degradable millineedles incorporated into the system could deliver model molecules to the esophagus. For the extra-esophageal compartment, we developed a highly flexible macrostructure (mechanical metamaterial) that deforms into a cylindrical shape to safely pass through the esophagus and deploys into a fenestrated spherical shape in the stomach, capable of residing safely in the gastric cavity for weeks. The macrostructure uses thermoresponsive elements that dissociate when triggered with the endoscopic application of warm (55°C) water, allowing safe passage of the components through the GI tract. Our gastric-resident platform acts as a gram-level long-lasting drug delivery dosage form, releasing small-molecule drugs for 2 weeks. We anticipate that temperature-triggered systems could usher the development of the next generation of stents, drug delivery, and sensing systems housed in the GI tract.

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“…area under the curve -AUC) do MIC. Szczytowe stężenie w osoczu po doustnym podaniu leku osiąga się po 1-2 godzinach, po aplikacji dożylnej efekt jest szybszy -kilkuminutowy; przy czym profil stężeń w surowicy w obydwu przypadkach jest porównywalny [19,23].…”

Section: Charakterystyka Lewofloksacynyunclassified

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

Płusa¹

2016

Forum Zakażeń

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STRESZCZENIE: Klasyfikacja fluorochinolonów została oparta na spektrum mikrobiologicznym i cechach farmakokinetycznych kolejno wprowadzanych preparatów, które charakteryzowały się lepszymi właściwościami farmakodynamicznymi, w tym znaczną penetracją do wnę-trza makrofagów i miejsca toczącego się procesu zapalnego. Przeprowadzona porównaw-cza analiza lewofloksacyny i moksyfloksacyny wskazuje na ich skuteczność kliniczną w kontrolowaniu zakażeń układowych zarówno w obrębie układu oddechowego, jak i moczowego, zwłaszcza w przypadku lewofloksacyny. Z tego powodu obydwa preparaty znalazły się w obowiązujących obecnie rekomendacjach postępowania w zakażeniach. Narastająca oporność na antybiotyki zmusza do ich racjonalnego stosowania -zgodnego ze światowymi wytycznymi.SŁOWA KLUCZOWE: lewofloksacyna, moksyfloksacyna, zakażenie ABSTRACT: Classification of fluoroquinolones is based on the spectrum of microbiological and pharmacokinetic characteristics in turn introduced preparations, which were characterized by improved pharmacodynamic properties, including significant penetration into the macrophages and inflammatory tissue. Conducted a comparative analysis of levofloxacin and moxifloxacin indicates clinically effective in controlling systemic infections both within the respiratory tract and urinary tract, particularly levofloxacin. For this reason, two products had been included in the recommendations of conduct infections developed in recent years. Increasing antibiotic resistance forces to their rational use -in accordance with international guidelines. WSTĘP Wskazaniem do stosowania antybiotyków są stany zapalne wywołane przez drobnoustroje. W zależności od rodzaju patogenu, jego aktywności i wrażliwości na podawany preparat o działaniu hamującym rozwój lub zabijającym bakterie, uzyskuje się odpowiedni efekt kliniczny. Najważniej-szym elementem tego postępowania, poza charakterystyką patogenu, są cechy farmakokinetyczne stosowanego antybiotyku, w tym: jego spektrum działania, stopień penetracji do miejsca toczącego się procesu zapalnego, wykazywane interakcje z innymi cząsteczkami oraz bezpieczeństwo dla chorego [1]. Posiadana wiedza w tym zakresie jest bardzo pomocna przy podejmowaniu decyzji terapeutycznych. KLASYFIKACJA FLUOROCHINOLONÓWChinolony należą do czynników przeciwbakteryjnych zsyntetyzowanych w latach 60. XX wieku w wyniku modyfikacji podstawowej dwupierścieniowej chemicznej struktury. Współczesna klasyfikacja fluorochinolonów jest oparta na spektrum mikrobiologicznym i cechach farmakokinetycznych poszczególnych preparatów. Należy podkreślić, Artyku jest dost pny na zasadzie dozwolonego u ytku osobistego. Dalsze rozpowszechnianie (w tym umieszczanie w sieci) jest zabronione i stanowi powa ne naruszenie przepisów prawa autorskiego oraz grozi sankcjami prawnymi.

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Impact of poor compliance with levofloxacin and moxifloxacin on respiratory tract infection antimicrobial efficacy: A pharmacokinetic/pharmacodynamic simulation study

Cited by 13 publications

References 13 publications

A Retrospective Analysis of Probability of Target Attainment in Community-Acquired Pneumonia: Ceftaroline Fosamil Versus Comparators

A Retrospective Analysis of Probability of Target Attainment in Community-Acquired Pneumonia: Ceftaroline Fosamil Versus Comparators

Temperature-responsive biometamaterials for gastrointestinal applications

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

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