Pharmacokinetics of Colistin Methanesulfonate and Colistin in a Critically Ill Patient Receiving Continuous Venovenous Hemodiafiltration

Li, Jian; Rayner, Craig R.; Nation, Roger L.; Deans, Renae; Boots, Robert; Widdecombe, N; Douglas, Alexandra; Lipman, Jeffrey

doi:10.1128/aac.49.11.4814-4815.2005

Cited by 124 publications

(110 citation statements)

References 11 publications

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“…The reason for what we could not detect heteroresistance may be the fact that all the ICU isolates in the study were from the same clone. Detection of colistin heteroresistant A. baumannii provides a strong warning that colistin is used inappropriately [22] . Moreover, previous use of colistin might be a risk factor for a higher rate of heteroresistance [4] .…”

Section: Discussionmentioning

confidence: 99%

Investigation of Colistin Heteroresistance and Some Factors Affecting Heteroresistance in Carbapenem-Resistant A. baumannii Strains

Gazel¹,

Otkun²

2018

mjima

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Introduction: Colistin can be used in patients infected with carbapenem-resistant Acinetobacter baumannii complex (CR-ABC), but recently resistance to colistin and heteroresistance have been reported. In this study we aimed to investigate the colistin heteroresistance rates and the effects of colistin and its combinations on colistin heteroresistance/resistance development in CR-ABC strains in our hospital. Materials and Methods: Heteroresistance analysis was performed on CR-ABC isolates and standard ABC strain [American Type Culture Collection (ATCC) 19606)] strain. To investigate hidden heteroresistance, the isolates were exposed to colistin at sub-inhibitory concentrations. 'Time-kill' study was performed on the standard strain and a clinical strain for colistin. Serial passage test was performed to investigate the effects of drug combinations on heteroresistance/resistance development. Results: In the first heteroresistance analysis test, all strains were found to be non-heteroresistant. However, after sub-inhibitory exposure to colistin, colistin heteroresistance/resistance developed in all isolates. In serial passages, colistin-rifampicin and colistin-tigecycline (Col+Tig) combinations were found to be effective and prevented growth of colistin-resistant sub-populations even at sub-inhibitory doses. Colistin-gentamicin (Col+Gen) combination was not found to be effective against the clinical isolate while it was effective on ATCC strain. Colistin-fluconazole combination was found to be ineffective at all concentrations. Conclusion: In our study, it was shown that the strains which were detected to be non-heteroresistant could easily transform to heteroresistant/ resistant forms after exposure to colistin. Colistin-rifampicin and Col+Tig combinations were found to be effective and prevented the emergence of heteroresistance/resistance to colistin even at low concentrations. At low concentrations, Col+Gen combination was ineffective against the clinical ABC isolate. Colistin-fluconazole combination failed to inhibit the emergence of resistant bacteria. Heteroresistance or resistance to colistin may easily develop because of inappropriate use of this antibiotic. To prevent this condition, colistin should be administrated at appropriate doses and in combination with the suggested antibiotics. Keywords: Colistin, carbapenem, combination, heteroresistance, rifampin Giriş: Kolistin, karbapenem dirençli Acinetobacter baumannii kompleks (CR-ABC) enfeksiyonu olan hastalarda kullanılabilecek seçeneklerdendir, ancak son zamanlarda kolistin için de direnç ve heterodirenç bildirilmiştir. Bu çalışmada hastanemizde izole edilen CR-ABC suşlarında, kolistin heterojen direnç oranını ve kolistinin ve bu ilacın ikili kombinasyonlarının kolistin heterodirenç/direnç gelişimi üzerine etkilerini araştırmayı amaçladık. Gereç ve Yöntem: Karbapenem dirençli A. baumannii izolatları vve standart ABC suşu [American Type Culture Collection (ATCC) 19606] üzerinde heterojen direnç analizi yapıldı. Gizli heterodirenç/direnci ortaya çıkarabil...

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Section: Discussionmentioning

confidence: 99%

Investigation of Colistin Heteroresistance and Some Factors Affecting Heteroresistance in Carbapenem-Resistant A. baumannii Strains

Gazel¹,

Otkun²

2018

mjima

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“…Contemporary, reliable colistin pharmacokinetic (PK) data show a much lower concentration-time profile than previously described (12,14,16,18). For example, a report by Plachouras et al (18) shows sub-MIC colistin concentrations during the first few days of therapy in critically ill patients.…”

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confidence: 94%

Colistin Dosing and Nephrotoxicity in a Large Community Teaching Hospital

DeRyke

Crawford

Uddin

et al. 2010

Antimicrob Agents Chemother

158

142

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Thirty adult patients who received intravenous colistin (5.1 ؎ 2.4 mg/kg/day) were reviewed to evaluate dosing with respect to nephrotoxicity, which occurred in 10 (33%) patients within the first 5 days of treatment. Excessive colistin dosing was frequent (47%), often (71%) resulted from the use of actual body weight in obese patients, and was associated with higher rates of nephrotoxicity (80% versus 30%, P ‫؍‬ 0.019).

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“…While older studies did not find any effect of hemodialysis on colistimethate (64,112), the effect of highflux dialyzers is unknown. Similarly, there is negligible information concerning the effect of other forms of renal replacement therapy, including venovenous hemofiltration (105,150). With the increasing use of polymyxins, accurate pharmacokinetic data for these populations are sorely needed (101).…”

Section: Dosing Guidelinesmentioning

confidence: 99%

Polymyxins Revisited

et al. 2008

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SUMMARY The global emergence of multidrug-resistant gram-negative bacilli has spurred a renewed interest in polymyxins. Once discarded due to concerns regarding nephrotoxicity and neurotoxicity, polymyxins now hold an important role in the antibiotic armamentarium. However, more reliable information is needed to determine the optimal dosing of these agents. Also, unanswered questions regarding in vitro testing remain, including questions regarding the reliability of automated systems and the establishment of appropriate breakpoints for defining susceptibility. Most contemporary clinical studies examining the use of these agents have involved patients with infections due to multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains. It has been reassuring that polymyxin therapy for resistant bacteria has resulted in clinical responses and toxicity rates similar to those for carbapenem therapy for susceptible isolates. While most surveillance studies demonstrated high rates of susceptibility, several reports noted the emergence of polymyxin-resistant nosocomial pathogens. Polymyxins have assumed an important antibiotic niche for therapy for hospital-acquired infections; further studies defining the optimal use of these agents will likely extend the duration of their clinical usefulness.

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Pharmacokinetics of Colistin Methanesulfonate and Colistin in a Critically Ill Patient Receiving Continuous Venovenous Hemodiafiltration

Cited by 124 publications

References 11 publications

Investigation of Colistin Heteroresistance and Some Factors Affecting Heteroresistance in Carbapenem-Resistant A. baumannii Strains

Investigation of Colistin Heteroresistance and Some Factors Affecting Heteroresistance in Carbapenem-Resistant A. baumannii Strains

Colistin Dosing and Nephrotoxicity in a Large Community Teaching Hospital

Polymyxins Revisited

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