Validation of a colistin plasma concentration breakpoint as a predictor of nephrotoxicity in patients treated with colistin methanesulfonate

Horcajada, Juan Pablo; Sorlí, Luisa; Luque, S.; Benito, Natividad; Segura, Concepción; Campillo, Nuria E.; Montero, Milagro; Esteve, Erika; Mirelis, Beatriz; Pomar, Virginia; Cuquet, Jordi; Martí, Carmina; Garro, Pau; Grau, Santiago

doi:10.1016/j.ijantimicag.2016.08.020

Cited by 57 publications

(53 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is important to note that, unless the MIC of the infecting strain is well below the breakpoint, this target is very likely to be suboptimal for the systemic treatment of a lung infection . Third, it is considered unwise to target a higher plasma colistin C ss,avg because pharmacokinetic/toxicodynamic (PK/TD) analyses in patients demonstrated that concentrations greater than 2 mg/L are associated with an increase in both the incidence and severity of AKI . Therefore, the proposed target concentrations of colistin should be considered the maximal tolerable target.…”

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

“…Moreover, if therapy is unsuccessful, potential dire consequences may ensue (clinical ones for the patient concerned in addition to emergence of polymyxin resistance). In addition, based on the more abundant data for colistin, there are established relationships between plasma exposure and both antibacterial effect and risk of AKI . The therapeutic window is extremely narrow because plasma exposures required for antibacterial effect overlap those associated with increased AKI risk .…”

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

“…Undoubtedly, nephrotoxicity is the most clinically relevant and dose‐limiting adverse reaction of the polymyxins. The incidence of nephrotoxicity varies widely in the literature from 0% to more than 60% largely due to heterogeneous patient populations, differing definitions of nephrotoxicity, wide ranges of polymyxin doses administered, and differences in both severity of illness and the presence/absence of various other risk factors for the patients being studied . Contemporary studies, using commonly accepted polymyxin doses and AKI definitions, place the rate of associated nephrotoxicity in the 20–50% range for both polymyxins …”

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

“…Although clinical PK data support the need for dose adjustment in AKI for colistin, they do not for polymyxin B . It is a reasonable hypothesis that patients who develop AKI have “supratherapeutic” polymyxin plasma concentrations, but evidence from colistin studies suggests considerable overlap between the “therapeutic” and “nephrotoxic” plasma concentrations of polymyxins among patients who develop AKI . It is also important to note that AKI may be precipitated by sepsis arising from inadequate treatment of infection …”

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

“…29,30 Third, it is considered unwise to target a higher plasma colistin C ss,avg because pharmacokinetic/toxicodynamic (PK/TD) analyses in patients demonstrated that concentrations greater than 2 mg/L are associated with an increase in both the incidence and severity of AKI. [34][35][36] Therefore, the proposed target concentrations of colistin should be considered the maximal tolerable target. Finally, even though a plasma colistin C ss,avg less than 2 mg/L may be adequate for an isolate with a low MIC, the susceptibility of the organism is often not known at the initiation of therapy, and therefore, a target of 2 mg/L is appropriate when starting CMS.…”

Section: Is There a Recommended Pk/pd Therapeutic Target For Maximentioning

confidence: 99%

See 4 more Smart Citations

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti‐infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)

et al. 2019

View full text Add to dashboard Cite

The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram‐negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti‐Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin‐based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.

show abstract

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

Section: Clinical Questions and Recommendationsmentioning

confidence: 99%

Section: Is There a Recommended Pk/pd Therapeutic Target For Maximentioning

confidence: 99%

See 3 more Smart Citations

International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti‐infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP)

et al. 2019

View full text Add to dashboard Cite

show abstract

Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Polymyxins: Implications for Therapeutic Use

Nation

Forrest

2019

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

How to Manage Pseudomonas aeruginosa Infections

Papadimitriou‐Olivgeris

Jacot

Guéry

2022

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Infections with Pseudomonas aeruginosa have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. Diverse strategies range from killing (new antibiotics) to disarming (antivirulence) the pathogen. In this review, selected aspects of P. aeruginosa antimicrobial resistance and infection management will be addressed. Many studies have been performed to evaluate the risk factors for resistance and the potential consequences on mortality and attributable mortality. The review also looks at the mechanisms associated with resistance -P. aeruginosa is a pathogen presenting a large genome, and it can develop a large number of factors associated with antibiotic resistance involving almost all classes of antibiotics. Clinical approaches to patients with bacteremia, ventilator-associated pneumonia, urinary tract infections and skin soft tissue infections are discussed. Antibiotic combinations are reviewed as well as an analysis of pharmacokinetic and pharmacodynamic parameters to optimize P. aeruginosa treatment. Limitations of current therapies, the potential for alternative drugs and new therapeutic options are also discussed.

show abstract

Validation of a colistin plasma concentration breakpoint as a predictor of nephrotoxicity in patients treated with colistin methanesulfonate

Cited by 57 publications

References 10 publications

Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Polymyxins: Implications for Therapeutic Use

How to Manage Pseudomonas aeruginosa Infections

Contact Info

Product

Resources

About