Pharmacokinetics and Penetration of Sitafloxacin into Alveolar Epithelial Lining Fluid in Critically Ill Thai Patients with Pneumonia

Paiboonvong, Taniya; Nosoongnoen, Wichit; Sathirakul, Korbtham; Tangsujaritvijit, Viratch; Kaemapairoj, Jaipak; Tragulpiankit, Pramote; Montakantikul, Preecha

doi:10.1128/aac.00800-19

Cited by 8 publications

(6 citation statements)

References 13 publications

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“…Sitafloxacin is a desfluoroquinolone antibiotic currently available in Thailand and Japan and has a broad spectrum in vitro activity against quinolone-resistant Gram-positive and Gram-negative organisms [75]. No studies have evaluated the intrapulmonary PK of sitafloxacin in healthy subjects; however, Paiboonvong and colleagues evaluated sitafloxacin ELF penetration in 12 critically ill patients with pneumonia (Table 5) [76]. The mean sitafloxacin AUC 8 for plasma and ELF were 5.58 µg•h/mL and 4.77 µg•h/mL, respectively.…”

Section: Sitafloxacinmentioning

confidence: 99%

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Drwiega

Rodvold

2021

Clin Pharmacokinet

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A comprehensive review of drug penetration into pulmonary epithelial lining fluid (ELF) was previously published in 2011. Since then, an extensive number of studies comparing plasma and ELF concentrations of antibacterial agents have been published and are summarized in this review. The majority of the studies included in this review determined ELF concentrations of antibacterial agents using bronchoscopy and bronchoalveolar lavage, and this review focuses on intrapulmonary penetration ratios determined with area under the concentration-time curve from healthy human adult studies or pharmacokinetic modeling of various antibacterial agents. If available, pharmacokinetic/pharmacodynamic parameters determined from preclinical murine infection models that evaluated ELF concentrations are also provided. There are also a limited number of recently published investigations of intrapulmonary penetration in critically ill patients with lower respiratory tract infections, where greater variability in ELF concentrations may exist. The significance of these changes may impact the intrapulmonary penetration in the setting of infection, and further studies relating ELF concentrations to clinical response are needed. Phase I drug development programs now include assessment of initial pharmacodynamic target values for pertinent organisms in animal models, followed by evaluation of antibacterial penetration into the human lung to assist in dosage selection for clinical trials in infected patients. The recent focus has been on β-lactam agents, including those in combination with β-lactamase inhibitors, particularly due to the rise of multidrug-resistant infections. This manifests as a large portion of the review focusing on cephalosporins and carbapenems, with or without β-lactamase inhibitors, in both healthy adult subjects and critically ill patients with lower respiratory tract infections. Further studies are warranted in critically ill patients with lower respiratory tract infections to evaluate the relationship between intrapulmonary penetration and clinical and microbiological outcomes. Our clinical research experience with these studies, along with this literature review, has allowed us to outline key steps in developing and evaluating dosage regimens to treat extracellular bacteria in lower respiratory tract infections.

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Section: Sitafloxacinmentioning

confidence: 99%

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Drwiega

Rodvold

2021

Clin Pharmacokinet

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“…Sitafloxacin has shown good in vitro activity against MDR CRAB. It has also been shown to penetrate well into the epithelial lining fluid in patients who are critically ill with pneumonia [15].…”

Section: Introductionmentioning

confidence: 99%

Clinical Efficacy of Sitafloxacin–Colistin–Meropenem and Colistin–Meropenem in Patients with Carbapenem-Resistant and Multidrug-Resistant Acinetobacter baumannii Hospital-Acquired Pneumonia (HAP)/Ventilator-Associated Pneumonia (VAP) in One Super-Tertiary Hospital in Bangkok, Thailand: A Randomized Controlled Trial

Wantanatavatod,

Wongkulab

2024

Antibiotics

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Background: Carbapenem-resistant A. baumannii (CRAB) hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) is now a therapeutic problem worldwide. Method: An open-label, randomized, superiority, single-blind trial was conducted in Rajavithi Hospital, a super-tertiary care facility in Bangkok, Thailand. CRAB HAP/VAP patients were randomly assigned to receive either sitafloxacin–colistin–meropenem or colistin–meropenem. Outcomes in the two groups were then assessed with respect to mortality, clinical response, and adverse effects. Result: Between April 2021 and April 2022, 77 patients were treated with combinations of either sitafloxacin plus colistin plus meropenem (n = 40) or colistin plus meropenem (n = 37). There were no significant differences between the two groups with respect to all-cause mortality rates at 7 days and 14 days (respectively, 7.5% vs. 2.7%; p = 0.616, and 10% vs. 10%; p = 1). Patients who received sitafloxacin–colistin–meropenem showed improved clinical response compared with patients who received colistin–meropenem in terms of both intention-to-treat (87.5% vs. 62.2%; p = 0.016) and per-protocol analysis (87.2% vs. 67.7%; p = 0.049). There were no significant differences between the two groups with respect to adverse effects. Conclusions: Adding sitafloxacin as a third agent to meropenem plus colistin could improve clinical outcomes in CRAB HAP/VAP with little or no impact on adverse effects. In short, sitafloxacin–meropenem–colistin could be another therapeutic option for combatting CRAB HAP/VAP.

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“…Its population pharmacokinetic model and PK/PD index have also been studied ( Tanigawara et al, 2013 ). A key feature of sitafloxacin is its excellent penetration into the epithelial lining fluid (ELF) of critically ill patients with pneumonia; according to the data of Paiboonvong et al, the AUC0–8 h of ELF/unbound plasma ratio was 0.85 ( Paiboonvong et al, 2019 ). Moreover, sitafloxacin in combination with colistin can decrease the MIC values of either colistin or sitafloxacin.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic (PK/PD) simulation for dosage optimization of colistin and sitafloxacin, alone and in combination, against carbapenem-, multidrug-, and colistin-resistant Acinetobacter baumannii

Rodjun,

Montakantikul,

Houngsaitong

et al. 2023

Front. Microbiol.

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To the best of our knowledge, to date, no study has investigated the optimal dosage regimens of either colistin or sitafloxacin against drug-resistant Acinetobacter baumannii (A. baumannii) infections by using specific parameters. In the current study, we aimed to explore the optimal dosage regimens of colistin and sitafloxacin, either in monotherapy or in combination therapy, for the treatment of carbapenem-, multidrug-, and colistin-resistant A. baumannii infections. A Monte Carlo simulation was applied to determine the dosage regimen that could achieve the optimal probability of target attainment (PTA) and cumulative fraction of response (CFR) (≥90%) based on the specific parameters of each agent and the minimal inhibitory concentration (MIC) of the clinical isolates. This study explored the dosage regimen of 90, 50, 30, and 10 mL/min for patients with creatinine clearance (CrCL). We also explored the dosage regimen for each patient with CrCL using combination therapy because there is a higher possibility of reaching the desired PTA or CFR. Focusing on the MIC90 of each agent in combination therapy, the dosage regimen for colistin was a loading dose of 300 mg followed by a maintenance dose ranging from 50 mg every 48 h to 225 mg every 12 h and the dosage regimen for sitafloxacin was 325 mg every 48 h to 750 mg every 12 h. We concluded that a lower-than-usual dose of colistin based on specific pharmacokinetic data in combination with a higher-than-usual dose of sitafloxacin could be an option for the treatment of carbapenem-, multidrug-, and colistin-resistant. A. baumannii. The lower dose of colistin might show a low probability of adverse reaction, while the high dose of sitafloxacin should be considered. In the current study, we attempted to find if there is a strong possibility of drug selection against crucial drug-resistant pathogen infections in a situation where there is a lack of new antibiotics. However, further study is needed to confirm the results of this simulation study.

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Pharmacokinetics and Penetration of Sitafloxacin into Alveolar Epithelial Lining Fluid in Critically Ill Thai Patients with Pneumonia

Cited by 8 publications

References 13 publications

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update

Pharmacokinetic/pharmacodynamic (PK/PD) simulation for dosage optimization of colistin and sitafloxacin, alone and in combination, against carbapenem-, multidrug-, and colistin-resistant Acinetobacter baumannii

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