Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseudomonas aeruginosa

Furtado, Guilherme Henrique Campos; d’Azevedo, Pedro Alves; Santos, Anderson Fernandes; Gales, Ana Cristina; Pignatari, Antônio Carlos Campos; Medeiros, Eduardo Alexandrino

doi:10.1016/j.ijantimicag.2007.05.017

Cited by 78 publications

(65 citation statements)

References 17 publications

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“…In previous reports, nephrotoxicity was the most common adverse effect of colistin therapy (18,20,24); however, recent studies reported lower nephrotoxicity rates in association with colistin use (14,27). In our study, we observed nephrotoxicity only in one patient which is similar to report of Falagas et al (27) in 2009.…”

Section: Discussionsupporting

confidence: 88%

“…Furtado reported the lowest effectiveness rate with colistin therapy for the treatment of nosocomial pneumonia due to MDR -P. aeruginosa (18). In our study, 7 patients died during the therapy and the most common diagnosis was pneumoniae in three patients and the most common identified microorganism was P. aeruginosa in three patients.…”

Section: Discussionmentioning

confidence: 52%

“…Few studies have investigated the clinical efficacy and safety of colistin use in children. It has been reported in previous studies that the effectiveness rates with colistin therapy were 47-88% (15,(18)(19)(20).…”

Section: Discussionmentioning

confidence: 94%

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Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

Karaaslan¹,

Çağan²,

Kadayıfçı³

et al. 2016

Balkan Med J

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 52%

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Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

Karaaslan¹,

Çağan²,

Kadayıfçı³

et al. 2016

Balkan Med J

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“…Nevertheless, it will continue to be used clinically until less toxic agents against multidrug-resistant bacteria become available (15)(16)(17). We previously showed that polymyxin B has a high affinity to renal tissue, which might be correlated to its nephrotoxic potential (8,9).…”

mentioning

confidence: 99%

Uptake of Polymyxin B into Renal Cells

Abdelraouf

Chang

Yin

et al. 2014

Antimicrob Agents Chemother

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Polymyxin B is increasingly used as a treatment of last resort against multidrug-resistant Gram-negative infections. Using a mammalian kidney cell line, we demonstrated that polymyxin B uptake into proximal tubular epithelial cells was saturable and occurred primarily through the apical membrane, suggesting the involvement of transporters in the renal uptake of polymyxin B. Megalin might play a role in the uptake and accumulation of polymyxin B into renal cells. Multidrug-resistant Gram-negative infections are disseminating worldwide (1-3). This has necessitated the use of systemic polymyxin B as a treatment of last resort, despite the risk of nephrotoxicity (4-6). Polymyxin B is a polypeptide antibiotic commercially available as a mixture of several closely related cyclic amphiphilic molecules, of which polymyxin B1 (PB1) is the most abundant component (7). Our group previously studied the nephrotoxicity and renal disposition of polymyxin B in a rat model (8,9). We showed that polymyxin B had a tendency to persist in the kidneys (8). Using a dose fractionation design, we have also demonstrated the saturation of renal uptake with a clinically relevant dosing exposure (9), which suggested that the renal uptake of polymyxin B was unlikely a passive process. In addition, histological examination showed that renal injury was predominantly confined to the proximal tubular epithelial cells of the renal cortex. Based on these results, we postulated that polymyxin B was taken up primarily by proximal tubular epithelial cells. Collectively, these observations suggest a selective uptake process into renal cells, which can play a prominent role in the nephrotoxic potential of polymyxin B. The objective of this study was to characterize the cell uptake of polymyxin B in vitro. Understanding the mechanism of renal uptake might provide useful insights into minimizing the accumulation of polymyxin B and thus reducing its nephrotoxic potential.(This study was presented in part at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Denver, CO, 10 -13 September 2013 [10].) Polymyxin B sulfate which met U.S. Pharmacopeia (USP) testing specifications, gentamicin sulfate (USP), and piperacillin sodium powder were purchased from Sigma-Aldrich (St. Louis, MO). A fluorescent polymyxin B derivative, polymyxin B Bodipy FL conjugate (FLPB), was purchased from Life Technologies (Grand Island, NY). Prior to each experiment, a fresh stock of each drug (100 mM, titrated to pH 5 by NaOH) was made with Dulbecco's phosphate-buffered saline (DPBS) with calcium and magnesium (Mediatech, Inc., Manassas, VA). Hanks' balanced salt solution (HBSS) was purchased from Sigma, supplemented with NaHCO 3 , glucose, and HEPES, and adjusted to pH 7.4 with NaOH at room temperature. Porcine kidney proximal tubular epithelial (LLC-PK1) cells were purchased from the ATCC (Manassas, VA). The cells were grown in medium 199 (Lonza, Walkersville, MD) supplemented with 3% fetal bovine serum (Thermo Scientific, Rockford, IL), 1% minimal essential...

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“…THE SPECIAL MICROBIOLOGY LABORATORY-UNIFESP TO THE CHARACTERIZATION OF NEW MECHANISM OF GRAM-NEGATIVE RESISTANCE TO CARBAPENENS As previously stated, multidrug resistance among Acinetobacter baumannii and Pseudomonas aeruginosa strains, particularly to the potent group of beta-lactam antibiotics carbapenems, is rising rapidly in Brazil. Invasive infections caused by the both mentioned species of bacteria are usually only susceptible to the antimicrobial group of polymyxins and are responsible for high morbidity and mortality rates among hospitalized patients (Furtado et al 2007). The mechanism of resistance to carbapenems was originally described as related to the loss of a membrane porine, impairing the transportation of the drug to its target of action.…”

Section: Contributions Of the Special Microbiology Laboratory-unifespmentioning

confidence: 99%

Surveillance programs for detection and characterization of emergent pathogens and antimicrobial resistance: results from the Division of Infectious Diseases, UNIFESP

Colombo

Janini

Salomão

et al. 2009

An. Acad. Bras. Ciênc.

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Several epidemiological changes have occurred in the pattern of nosocomial and community acquired infectious diseases during the past 25 years. Social and demographic changes possibly related to this phenomenon include a rapid population growth, the increase in urban migration and movement across international borders by tourists and immigrants, alterations in the habitats of animals and arthropods that transmit disease, as well as the raise of patients with impaired host defense abilities. Continuous surveillance programs of emergent pathogens and antimicrobial resistance are warranted for detecting in real time new pathogens, as well as to characterize molecular mechanisms of resistance. In order to become more effective, surveillance programs of emergent pathogens should be organized as a multicenter laboratory network connected to the main public and private infection control centers. Microbiological data should be integrated to guide therapy, adapting therapy to local ecology and resistance patterns. This paper presents an overview of data generated by the Division of Infectious Diseases, Federal University of São Paulo, along with its participation in different surveillance programs of nosocomial and community acquired infectious diseases.

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Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseudomonas aeruginosa

Cited by 78 publications

References 17 publications

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients

Uptake of Polymyxin B into Renal Cells

Surveillance programs for detection and characterization of emergent pathogens and antimicrobial resistance: results from the Division of Infectious Diseases, UNIFESP

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