Suboptimal Ciprofloxacin Dosing as a Potential Cause of Decreased <i>Pseudomonas aeruginosa</i> Susceptibility in Children with Cystic Fibrosis

Guillot, Emmanuelle; Sermet, Isabelle; Ferroni, Agnès; Chhun, Stéphanie; Pons, Gérard; Zahar, Jean‐Ralph; Jullien, Vincent

doi:10.1592/phco.30.12.1252

Cited by 17 publications

(13 citation statements)

References 25 publications

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“…The findings of these surveys suggest that recommended doses and dosing regimens are not used by a substantial number of CF centers despite CFF, European, and UK CF Trust Working Group recommendations, literature confirming the efficacy and safety of higher than Food and Drug Administration (FDA) approved doses for beta‐lactam agents and once‐daily aminoglycosides, and the ease of once‐daily aminoglycoside dosing12, 18, 19, 33–42 (Table 1). Possible explanations as to why CF practitioners are not following recommended doses and dosing regimens were discussed in the first article of the series by Zobell et al13 These surveys suggest that additional education and implementation strategies are needed to assist CF practitioners in optimizing the treatment of APE.…”

Section: Results Of Cf Antibiotic Utilization Surveysmentioning

confidence: 99%

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: VI. Executive summary

Zobell

Young

Waters

et al. 2013

Pediatric Pulmonology

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Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an overview of the classes of intravenous anti-pseudomonal antibiotics, the findings of anti-pseudomonal antibiotic utilization surveys, the current antibiotic dosing recommendations from the U.S. and Europe, and the pharmacokinetic (PK) and pharmacodynamic (PD) differences between CF and non-CF individuals. Anti-pseudomonal antibiotic classes include beta-lactams, aminoglycosides, fluoroquinolones, and colistimethate sodium. Recent surveys of antibiotic utilization in CF Foundation-accredited care centers have shown that a large number of centers are not following recommended dosing strategies despite published recommendations in the U.S. and Europe. The recommended doses for anti-pseudomonal antibiotics may be higher than FDA-approved doses due to PK and PD differences. As a large portion of CF patients will not regain their lung function following an APE, it seems possible that currently available anti-pseudomonal agents are being used sub-optimally. As new anti-pseudomonal agents are not currently available, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat pulmonary exacerbations in an effort to improve outcomes for CF patients infected with Pseudomonas aeruginosa.

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Section: Results Of Cf Antibiotic Utilization Surveysmentioning

confidence: 99%

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: VI. Executive summary

Zobell

Young

Waters

et al. 2013

Pediatric Pulmonology

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“…alternative for treating Pseudomonas aeruginosa in 7/22 of our patients. Subtherapeutic concentrations of fluoroquinolones select resistant Pseudomonas strains (12,25). Therefore, higher p.o.…”

Section: Discussionmentioning

confidence: 99%

“…Yet, resistance rates of different uropathogens for fluoroquinolones are rapidly rising, probably at least partly due to inappropriate usage (11). Fluoroquinolones are concentration-dependent bacterial killers, which implies that sufficient drug concentrations are essential both for exerting antibiotic effects and for reducing antimicrobial resistance (12,13). Therefore, in treating UTI, sufficient concentrations of antibiotics in urine are essential for bacterial eradication.…”

mentioning

confidence: 99%

Results of a Multicenter Population Pharmacokinetic Study of Ciprofloxacin in Children with Complicated Urinary Tract Infection

Meesters

Michelet

Mauel

et al. 2018

Antimicrob Agents Chemother

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Resistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated urinary tract infections. Children to whom ciprofloxacin was prescribed, intravenous (10 to 15 mg/kg body weight every 12 h) or (15 to 20 mg/kg every 12 h), were enrolled. One hundred eight serum and 119 urine samples were obtained during 10 intravenous and 13 oral courses of ciprofloxacin in 22 patients (age range, 0.31 to 15.51 years). A one-compartment model best described our data. Fat-free mass and glomerular filtration rate (estimated by a formula using cystatin C and creatinine), standardized for body surface area, were significant covariates for ciprofloxacin clearance. In our population, ciprofloxacin clearance is 0.16 to 0.43 liter/h/kg of body weight, volume of distribution 0.06 to 2.88 liters/kg, and bioavailability 59.6%. All of our patients had a clinical cure of their infection. Based on target attainment simulations across doses, all children reached the pharmacodynamic target for, but on average only 53% did for and 3% for, at the 15-mg/kg oral dose. For treating urinary tract infections caused by , oral doses should be at least 20 mg/kg. Furthermore, in our population, fat-free mass and kidney function should be considered, as they prove to be significant covariates for ciprofloxacin clearance and, hence, exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT02598362.).

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“…the lung epithelial lining fluid (ELF), is low. 13 Thus, an aerosolized form of CIP that could enable high concentrations in the lung to be achieved and, at the same time, a lower plasma concentration, would be of interest.…”

Section: Introductionmentioning

confidence: 99%

Ciprofloxacin-Loaded Inorganic–Organic Composite Microparticles To Treat Bacterial Lung Infection

et al. 2015

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Ciprofloxacin (CIP) is an antibiotic that has been clinically trialed for the treatment of lung infections by aerosolization. However, CIP is rapidly systemically absorbed after lung administration, increasing the risk for subtherapeutic pulmonary concentrations and resistant bacteria selection. In the presence of calcium, CIP forms complexes that reduce its oral absorption. Such complexation may slow down CIP absorption from the lung thereby maintaining high concentration in this tissue. Thus, we developed inhalable calcium-based inorganic-organic composite microparticles to sustain CIP within the lung. The aerodynamics and micromeritic properties of the microparticles were characterized. FTIR and XRD analysis suggest that the inorganic component of the particles comprised amorphous calcium carbonate and amorphous calcium formate, and that CIP and calcium interact in a 1:1 stoichiometry in the particles. CIP was completely released from the microparticles within 7 h, with profiles showing a slight dependence on pH (5 and 7.4) compared to the dissolution of pure CIP. Transport studies of CIP across Calu-3 cell monolayers, in the presence of various calcium concentrations, showed a decrease of up to 84% in CIP apparent permeability. The apparent minimum inhibitory concentration of CIP against Pseudomonas aeruginosa and Staphylococcus aureus was not changed in the presence of the same calcium concentration. These results indicate that the designed particles should provide sustained levels of CIP with therapeutic effect in the lung. With these microparticles, it should be possible to control CIP pharmacokinetics within the lung, based on controlled CIP release from the particles and reduced apparent permeability across the epithelial barrier due to the cation-CIP interaction.

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Suboptimal Ciprofloxacin Dosing as a Potential Cause of Decreased Pseudomonas aeruginosa Susceptibility in Children with Cystic Fibrosis

Cited by 17 publications

References 25 publications

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: VI. Executive summary

Optimization of anti‐pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: VI. Executive summary

Results of a Multicenter Population Pharmacokinetic Study of Ciprofloxacin in Children with Complicated Urinary Tract Infection

Ciprofloxacin-Loaded Inorganic–Organic Composite Microparticles To Treat Bacterial Lung Infection

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