Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections

Montero, Milagro; Horcajada, Juan Pablo; Sorlí, Luisa; Álvarez-Lerma, Francisco; Grau, Santiago; Riu, Marta; Sala, María; Knobel, Hernando

doi:10.1007/s15010-009-8342-x

Cited by 89 publications

(65 citation statements)

References 25 publications

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“…By contrast, in this study, higher doses of colistin were not related to a better clinical outcome. However, clinical response rate was similar to those reported by other authors [2,[25][26][27][28]. These results could be explained in part by the fact that only 16 patients had received higher CMS doses (3 million IU every 8 hours).…”

Section: Discussionsupporting

confidence: 89%

“…The reported rate of colistin-associated nephrotoxicity varies from 0% to 37% in older studies [2,3,20,21]. This variability could be the result of differences in the definitions of nephrotoxicity and in the dose and duration of treatment with CMS in earlier studies.…”

Section: Discussionmentioning

confidence: 99%

“…Rates of nephrotoxicity in recent studies designed to assess this outcome have ranged from 6% to 14% in some and from 32% to 55% in others [1][2][3][4]. However, despite the large number of publications, different nephrotoxicity definitions, differences in dosing schedules, and a lack of control of risk factors for nephrotoxicity have complicated an understanding of the real clinical relevance of this adverse effect [5].…”

Section: Introductionmentioning

confidence: 99%

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Clinical Effectiveness and Nephrotoxicity of Aerosolized Colistin Treatment in Multidrug-Resistant Gram-Negative Pneumonia

Park

Chung

et al. 2016

Korean J Crit Care Med

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Background: Data regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels. Methods: A prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (C min ) and 30 minutes after CMS infusion (C max ). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. Results: One hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, C min (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), C min (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When C min was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT. Conclusions: When using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. C min levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and C min might be a new useful tool to predict AKI.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical Effectiveness and Nephrotoxicity of Aerosolized Colistin Treatment in Multidrug-Resistant Gram-Negative Pneumonia

Park

Chung

et al. 2016

Korean J Crit Care Med

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“…Infections with carbapenem-resistant P. aeruginosa generally have a poorer prognosis than infections with carbapenem-sensitive P. aeruginosa (7). In addition, the efficacy of colistin against infections with carbapenem-resistant P. aeruginosa has not been established (8). Appropriate use of antimicrobial drugs is required to control the emergence of drug-resistant bacterial pathogens (9,10).…”

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confidence: 99%

Efficacy of High-Dose Meropenem (Six Grams per Day) in Treatment of Experimental Murine Pneumonia Induced by Meropenem-Resistant Pseudomonas aeruginosa

Oshima

Nakamura

Iwanaga

et al. 2017

Antimicrob Agents Chemother

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High-dose meropenem (MEPM; 6 g/day) has been approved as a treatment for purulent meningitis; however, little is known regarding its in vivo efficacy in refractory lower respiratory tract infections. The purpose of this study was to evaluate the efficacy of MEPM at 6 g/day in a murine model of severe pneumonia caused by MEPM-resistant Pseudomonas aeruginosa. Experimental pneumonia induced by MEPM-resistant P. aeruginosa was treated with normal-dose MEPM (150 mg/kg of body weight, simulating a 3-g/day regimen in humans) or high-dose MEPM (500 mg/kg, simulating a 6-g/day regimen in humans). Mice treated with high-dose MEPM showed significantly restored survival relative to that of untreated mice and tended to show a survival rate higher than that of mice treated with normal-dose MEPM. The viable bacterial counts (of two clinical isolates) in the lungs decreased significantly in mice treated with high-dose MEPM from those for untreated mice (P Ͻ 0.001) or mice treated with normal-dose MEPM (P, Ͻ0.01 and Ͻ0.05). The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was also significantly lower in mice treated with high-dose MEPM than in untreated mice. The free MEPM concentration in the epithelial lining fluid (ELF) exceeded 16 g/ml for 85 min in mice treated with high-dose MEPM, but not for mice treated with normal-dose MEPM. Our results demonstrate that high-dose MEPM (6 g/day) might provide better protection against pneumonia caused by MEPM-resistant strains of P. aeruginosa than the dose normally administered (less than 3 g/day).KEYWORDS high dose, meropenem, pharmacokinetics/pharmacodynamics, meropenem-resistant Pseudomonas aeruginosa P seudomonas aeruginosa is one of the major causes of hospital-acquired pneumonia (HAP) and opportunistic infections (1). HAP and bacteremia caused by P. aeruginosa can be fatal. A mortality rate of 47% has been reported for P. aeruginosa pneumonia patients. Mortality as a result of P. aeruginosa pneumonia is associated with a delay in initiating effective antimicrobial therapy and with multidrug-resistant P. aeruginosa (MDRP) (2, 3).Meropenem (MEPM) is an antimicrobial drug that is potent against P. aeruginosa; however, the incidence of MDRP has increased recently (4), and P. aeruginosa is the most common multidrug-resistant bacterial cause of hospital-acquired pneumonia

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“…2,4) Colistin was originally developed in Japan in the 1940s-1950s; however, initial studies reported adverse reactions, including nephrotoxicity or peripheral nervous system disorders. 5) Because of these adverse events and the introduction of safer antibiotics, clinical use of colistin was abandoned in Japan in 1990.…”

mentioning

confidence: 99%

Successful Colistin Treatment of Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Infection Using a Rapid Method for Determination of Colistin in Plasma: Usefulness of Therapeutic Drug Monitoring

Yamada

Ishiguro

Kenji

et al. 2015

Biological & Pharmaceutical Bulletin

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A 56-year-old woman with systemic lupus erythematosus had bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDRP). She was initially treated with imipenem-cilastatin, tobramycin, and aztreonam; however, MDRP was still detected intermittently in her plasma. Multidrug-susceptibility tests demonstrated that MDRP was susceptible only to colistin. Therefore, in addition to these antibiotics, the administration of intravenous colistin methanesulfonate, a prodrug formula of colistin, was started at a daily dose of 2.5 mg/kg (as colistin base activity). The initial dose setting was based on the patient's renal function (baseline creatinine clearance 32.7 mL/min). After initiating colistin, the patient's C-reactive protein levels gradually decreased. Blood cultures showed no evidence of MDRP on days 8, 14, and 22 after colistin initiation. However, the patient's renal function went from bad to worse owing to septic shock induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. A few days later, the trough plasma levels of colistin were 7.88 mg/L, which appeared to be higher than expected. After decreasing the colistin dose, the patient's renal function gradually improved. On the final day of colistin treatment, the plasma levels decreased to 0.60 mg/L. MDRP could not be detected in blood culture after colistin treatment. Therefore, we successfully treated a case of bloodstream infection due to MDRP by therapeutic drug monitoring (TDM) of colistin. It is suggested that the monitoring of blood colistin levels by liquid chromatography-tandem mass spectrometry can contribute to safer, more effective antimicrobial therapy of MDRP because TDM facilitates quick decisions on dose adjustments.

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Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections

Abstract: Colistin is a safe option for the treatment of MDRP infections, with acceptable clinical outcomes. However, bacteriological eradication is difficult to achieve, especially in COPD patients.

Cited by 89 publications

References 25 publications

Clinical Effectiveness and Nephrotoxicity of Aerosolized Colistin Treatment in Multidrug-Resistant Gram-Negative Pneumonia

Clinical Effectiveness and Nephrotoxicity of Aerosolized Colistin Treatment in Multidrug-Resistant Gram-Negative Pneumonia

Efficacy of High-Dose Meropenem (Six Grams per Day) in Treatment of Experimental Murine Pneumonia Induced by Meropenem-Resistant Pseudomonas aeruginosa

Successful Colistin Treatment of Multidrug-Resistant <i>Pseudomonas aeruginosa</i> Infection Using a Rapid Method for Determination of Colistin in Plasma: Usefulness of Therapeutic Drug Monitoring

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