Ecology of Pseudomonas aeruginosa in patients with cystic fibrosis

Horrevorts, A. M.; Borst, Jan Willem; Puyk, R. J. T.; Ridder, Rogier de; Dzoljic-Danilovic, G.; Degener, John E.; Kerrebijn, K. F.; Michel, M. F.

doi:10.1099/00222615-31-2-119

Cited by 19 publications

(14 citation statements)

References 8 publications

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“…Also, in patients with respiratory tract infections due to P. aeruginosa, in spite of intensive treatment with ciprofloxacin bacterial persistence has been described by various authors (1,7,12,16,31). Successful eradication of bacteria from lung tissue chronically infected with P. aeruginosa is probably hampered by various factors.…”

Section: Discussionmentioning

confidence: 99%

Ciprofloxacin in Polyethylene Glycol-Coated Liposomes: Efficacy in Rat Models of Acute or Chronic Pseudomonas aeruginosa Infection

Bakker-Woudenberg

Kate

Guo³

et al. 2002

Antimicrob Agents Chemother

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In a previous study in experimental Klebsiella pneumoniae pneumonia, the therapeutic potential of ciprofloxacin was significantly improved by encapsulation in polyethylene glycol-coated ("pegylated") long-circulating (STEALTH) liposomes. Pegylated liposomal ciprofloxacin in high doses was nontoxic and resulted in relatively high and sustained ciprofloxacin concentrations in blood and tissues, and hence an increase in the area under the plasma concentration-time curve (AUC). These data correspond to data from animal and clinical studies showing that for fluoroquinolones the AUC/MIC ratio is associated with favorable outcome in serious infections. Clinical failures and the development of resistance are observed for marginally susceptible organisms like Pseudomonas aeruginosa and for which sufficient AUC/MIC ratios cannot be achieved. In the present study the therapeutic efficacy of pegylated liposomal ciprofloxacin was investigated in two rat models of Pseudomonas aeruginosa pneumonia. In the acute model pneumonia developed progressively, resulting in a rapid onset of septicemia and a high mortality rate. Ciprofloxacin twice daily for 7 days was not effective at doses at or below the maximum tolerated dose (MTD). However, pegylated liposomal ciprofloxacin either at high dosage or given at low dosage in combination with free ciprofloxacin on the first day of treatment was fully effective (100% survival). Obviously, prolonged concentrations of ciprofloxacin in blood prevented death of the animals due to early-stage septicemia in this acute infection. However, bacterial eradication from the left lung was not effected. In the chronic model, pneumonia was characterized by bacterial persistence in the lung without bacteremia, and no signs of morbidity or mortality were observed. Ciprofloxacin administered for 7 days at the MTD twice daily resulted in killing of more than 99% of bacteria in the lung; this result can also be achieved with pegylated liposomal ciprofloxacin given once daily. Complete bacterial eradication is never observed.Many in vitro studies as well as studies in animal models of infection and human infections have investigated the efficacy of fluoroquinolones. The area under the plasma concentrationtime curve (AUC) and the peak plasma drug concentration, both in relation to the MIC of the pathogen, have been demonstrated to be of primary importance for successful outcome (33). For example, in several clinical trials in patients with nosocomially acquired pneumonia, a 24-h AUC/MIC ratio of at least 100 to 125 (14, 15, 19) or a peak plasma drug concentration/MIC ratio of 10 or more (26) was closely linked to clinical and microbiological cure in seriously ill patients treated with intravenous ciprofloxacin. Most treatment failures with ciprofloxacin were a consequence of high MIC, low AUC, or both. A peak plasma drug concentration/MIC ratio of 10 or 20 has been shown both in vitro and in vivo to prevent the emergence of resistant mutants during therapy with fluoroquinolones.These observations in clinical s...

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Section: Discussionmentioning

confidence: 99%

Ciprofloxacin in Polyethylene Glycol-Coated Liposomes: Efficacy in Rat Models of Acute or Chronic Pseudomonas aeruginosa Infection

Bakker-Woudenberg

Kate

Guo³

et al. 2002

Antimicrob Agents Chemother

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“…The initially acquired strain persisted over the whole study period; only two patients lost their clone after 3 years. Horrevorts et al [3] monitored 15 CF patients over periods up to 5 years, applying serotyping, phage typing, and pyocin typing. They found that, generally, one serotype predominated and that the colonization with P. aeruginosa was quite constant.…”

Section: Discussionmentioning

confidence: 99%

Epidemiologic characterization of Pseudomonas aeruginosa in patients with cystic fibrosis

Spencker¹,

Haupt²,

Claros³

et al. 2000

Clinical Microbiology and Infection

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“…In this case, again, antibiotic resistance mechanisms evolved coincidentally with the introduction of new antibiotic derivatives, compromising the most effective treatments (such as the ␤-lactams and aminoglycosides). P. aeruginosa is of considerable concern for patients with cystic fibrosis (76); the pathogen is highly persistent and can avoid human immune defenses. Resistance development is associated with the lengthy antibiotic treatment of cystic fibrosis patients.…”

Section: Superbugs and Superresistancementioning

confidence: 99%

Origins and Evolution of Antibiotic Resistance

Davies

2010

Microbiol Mol Biol Rev

4,762

3,296

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SUMMARY Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

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Ecology of Pseudomonas aeruginosa in patients with cystic fibrosis

Cited by 19 publications

References 8 publications

Ciprofloxacin in Polyethylene Glycol-Coated Liposomes: Efficacy in Rat Models of Acute or Chronic Pseudomonas aeruginosa Infection

Ciprofloxacin in Polyethylene Glycol-Coated Liposomes: Efficacy in Rat Models of Acute or Chronic Pseudomonas aeruginosa Infection

Epidemiologic characterization of Pseudomonas aeruginosa in patients with cystic fibrosis

Origins and Evolution of Antibiotic Resistance

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