Development of resistance in Pseudomonas aeruginosa obtained from patients with cystic fibrosis at different times

Spencker, F.-B.; Staber, L.; Lietz, T.; Schille, R.; Rodloff, Arne C.

doi:10.1046/j.1469-0691.2003.00534.x

Cited by 22 publications

(11 citation statements)

References 21 publications

(20 reference statements)

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“…Hence, our results could provide a pharmacologic explanation for the increase in the ciprofloxacin MIC against P. aeruginosa secondary to ciprofloxacin treatment that was evidenced in children with cystic fibrosis. 5 Of note, this progressive decrease in the susceptibility to ciprofloxacin specifically involved bacterial strains with a baseline MIC greater than 0.125 mg/L, which seems to confirm the results of our simulations.…”

Section: Discussionsupporting

confidence: 87%

“…Our results showed that the current ciprofloxacin dosage recommendations are probably suboptimal in patients with cystic fibrosis-more specifically, for ciprofloxacin MICs higher than 0.125 mg/L against P. aeruginosa, which is lower than the clinical breakpoint of 0.5 mg/L defined by the European Society of Clinical Microbiology and Infectious Diseases 27 -as evidenced by an increase in the geometric mean of the MIC in patients with cystic fibrosis. 5 Thus, it appears that a clinically relevant proportion of children with cystic fibrosis who have infections due to P. aeruginosa may receive suboptimal treatment, even if the bacterial strain is considered susceptible to ciprofloxacin (according to the European guidelines 27 ). Hence, our results could provide a pharmacologic explanation for the increase in the ciprofloxacin MIC against P. aeruginosa secondary to ciprofloxacin treatment that was evidenced in children with cystic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, after 2 years of successive ciprofloxacin treatment in 34 children with cystic fibrosis, the geometric mean of the ciprofloxacin minimum inhibitory concentration (MIC) against P. aeruginosa increased from 0.24 to 0.38 mg/L. 5 This phenomenon could be deleterious and could critically compromise the success of treatment of pulmonary infections due to P. aeruginosa in the future if the MICs continue to rise and reach values close to the clinical breakpoint (0.5 mg/L). Experimental models have shown that the risk of acquiring resistance to fluoroquinolones is related to low exposure to the drug.…”

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confidence: 99%

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

et al. 2010

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These results provide a pharmacologic hypothesis-that the current dosing recommendations of ciprofloxacin for cystic fibrosis children may be suboptimal-to explain the decrease in the susceptibility of P. aeruginosa to ciprofloxacin observed in children with cystic fibrosis. These results need to be confirmed in prospective pharmacokinetic-pharmacodynamic studies performed in children with cystic fibrosis in order to determine whether higher doses, with or without therapeutic drug monitoring, or a lower clinical breakpoint could be considered in this population.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

et al. 2010

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“…3 We noticed several cases of acute renal failure in our adult patients associated with the concurrent use of potentially nephrotoxic antibiotics, and this was also reported elsewhere. 4,5 The increasing prevalence of antibiotic multiresistance in Pseudomonas aeruginosa strains in CF patients, 6,7 and in particular that associated with epidemic strains, 8,9 may increase the requirements for nephrotoxic antibiotics. Indeed, the most prevalent epidemic strain in the United Kingdom (UK) (the Liverpool epidemic strain; LES) 10 is common in our unit and is frequently sensitive only to tobramycin and colistin sulphomethate, 11 both of which are potentially nephrotoxic.…”

Section: Introductionmentioning

confidence: 99%

Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use

et al. 2004

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Although there are reports of cases of acute renal failure occurring in cystic fibrosis (CF) patients, usually in association with the use of nephrotoxic antibiotic therapy, there have been no studies of renal function in this patient group. We hypothesized that long-term use of intravenous (IV) nephrotoxic antibiotics (aminoglycosides and colistin sulphomethate) may contribute to renal disease in CF patients. In a prospective study, we assessed creatinine clearance as an index of renal function with two techniques (24-hr urine collections and the Cockroft-Gault formula) in a group of 80 stable adult CF outpatients chronically infected with Pseudomonas aeruginosa but with no history of preceding renal disease. Using a multiple linear regression model, we evaluated their renal function in terms of their lifetime IV use of aminoglycosides and colistin. Between 31% (Cockroft-Gault formula method) and 42% (24-hr urine collection method) of patients had a creatinine clearance below normal range. Using either method, there was a strong correlation between aminoglycoside use and diminishing renal function (r=- 0.32, P=0.0055), which was potentiated by the coadministration of colistin (r=- 0.42, P<0.0002). However, there was no correlation with colistin when used in combination with other antibiotics alone (r=0.18, P=NS). Repeated IV aminoglycoside use in CF is associated with long-term renal damage. Although this effect is potentiated by colistin, colistin on its own in moderate doses does not appear to be nephrotoxic. IV aminoglycosides should be used cautiously in CF patients, with regular monitoring of renal function.

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“…Extended or continuous infusions increased the PTA for pathogens with elevated MIC, even as high as 8 to 12 μg/mL . This is invaluable in patients with CF because they usually have a history of previous exposure to antibiotics for both acute and chronic respiratory infections . Likely due to their repeated antibiotic exposures, reported antibiotic resistance rates are higher in children with CF.…”

Section: Clinical Pharmacology Optimizing Bedside Care Of Pediatric Imentioning

confidence: 99%

Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs

Lê

Bradley

2018

The Journal of Clinical Pharma

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The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age‐related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population‐based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta‐lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated.

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Development of resistance in Pseudomonas aeruginosa obtained from patients with cystic fibrosis at different times

Abstract: A trend towards an increase of the MICs against antipseudomonal agents was observed over a limited period of time. It is necessary to prevent this development possibly by employing suitable combinations of antibiotics and the introduction of new substances.

Cited by 22 publications

References 21 publications

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

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

Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use

Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs

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