Urinary Concentrations of Colistimethate and Formed Colistin after Intravenous Administration in Patients with Multidrug-Resistant Gram-Negative Bacterial Infections

Luque, Sònia; Escaño, Carol; Sorlí, Luisa; Li, Jian; Campillo, Nuria E.; Horcajada, Juan Pablo; Salas, E.; Grau, Santiago

doi:10.1128/aac.02595-16

Cited by 19 publications

(16 citation statements)

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“…Conversely, despite the small number of cases, in patients with BSI from the urinary tract we observed a lower mortality in those who received colistin-containing regimens compared to other regimens (33.3% vs 100%). This may be due to a rapid urinary excretion and higher concentration in the urinary tract of intravenously administered colistin [44]. Unfortunately, the clinical efficacy of colistin therapy is difficult to assess because some routine laboratory methods used for colistin susceptibility testing (in particular gradient tests) have a poor performance [45], and is not ever possible to determine if colistin has appropriate MIC.…”

Section: Discussionmentioning

confidence: 99%

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

et al. 2020

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Background: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). Methods: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intraabdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1-36]) versus those who died (48 h [IQR 5-108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188-0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p = 0.027), cardiovascular disease , p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006-1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p = 0.014) compared to colistin-containing regimens.Conclusions: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.

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Section: Discussionmentioning

confidence: 99%

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

et al. 2020

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“…Urinary concentrations of colistin after administration of CMS (mainly cleared by renal excretion) can be high because of conversion of CMS to colistin in the urinary tract. 4,43,55,56 In contrast, polymyxin B is predominantly cleared by nonrenal mechanisms with a median urinary recovery of 4.0% in patients. 44 Future Research Needs.…”

Section: Should I Preferentially Use One Polymyxinmentioning

confidence: 99%

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

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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.

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“…In the case of urinary tract infections, colistin is a good option because concentrations of formed colistin in urine are high (185). Moreover, and because of this, in urinary tract infections the colistin dose could be lower than in other invasive infections (190). However, no clinical data are available to confirm this option.…”

Section: Currently Available Antimicrobials For the Treatment Of Mdr mentioning

confidence: 99%

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

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SUMMARYIn recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR)Pseudomonas aeruginosahas become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options.In vitroandin vivotreatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDRP. aeruginosainfections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other “old” antimicrobials, such as certain β-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDRP. aeruginosastrains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDRP. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

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Urinary Concentrations of Colistimethate and Formed Colistin after Intravenous Administration in Patients with Multidrug-Resistant Gram-Negative Bacterial Infections

Cited by 19 publications

References 21 publications

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

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