Nephrotoxicity Associated with Intravenous Colistin (Colistimethate Sodium) Treatment at a Tertiary Care Medical Center

Hartzell, Joshua D.; Neff, Robert; Ake, Julie A; Howard, Robin S.; Olson, Stephen W.; Paolino, Kristopher; Vishnepolsky, Mark; Weintrob, Amy; Wortmann, Glenn

doi:10.1086/599225

Cited by 327 publications

(345 citation statements)

References 19 publications

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“…The most likely explanations of the higher rate of multi-drug resistance in this study could be because of the difference in the antibiotics used and the various definitions of multi-drug resistance. The high frequency of MDR isolates in this study could shift the treatment to the use of polymyxin as a last choice with its marked adverse effects [24,25]. One of the virulence mechanisms possessed by P. aeruginosa is known as TTSS, which is a syringe-like structure that allows the introduction of toxins (e.g., ExoS and ExoU) into target cell cytoplasm [26].…”

Section: Discussionmentioning

confidence: 98%

Molecular Detection of the VirulentExoUGenotype ofPseudomonas aeruginosaIsolated from Infected Surgical Incisions

Hassuna

2016

Surgical Infections

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Background: Pseudomonas aeruginosa is one of the major pathogens responsible for hospital-acquired infections, which harbor a wide array of virulence factors. The main aim of this study was to determine the frequency of the virulent ExoU genotype in relation to the ExoS genotype among isolated P. aeruginosa from infected surgical incisions, followed by phylogenetic analysis. Methods: A total of 66 P. aeruginosa isolates were identified by cultural and biochemical characteristics. All isolates were tested for antimicrobial susceptibility against the following antimicrobial agents: imipenem, amikacin, gentamicin, amoxycillin, cefotaxime, cefepime, and levofloxacin. Molecular detection of the ExoS and ExoU as well as two other virulence genes was done by polymerase chain reaction (PCR). Sequencing of ExoU gene and phylogenetic analysis was performed.Results: Approximately 81% of the isolated P. aeruginosa were multi-drug resistant. The ExoS genotype was more prevalent (63%) among the isolates than the ExoU genotype (18%), with 9% of the isolates possessing both toxins. LasB and AprA were detected in 63.6% and 27.2% of the isolates, respectively. An association was observed between the number of virulence genes and the presence of multi-drug resistance. All the ExoU were multi-drug resistant (MDR), whereas 71% of the ExoS were MDR. Phylogenetic analysis of ExoU gene showed a 99% similarity with four different strains. Conclusion: Despite the greater frequency of the ExoS genotype, the presence of the virulent MDR ExoU genotype isolates from surgical site infections is an alarming sign requiring further intervention and investigations.

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Section: Discussionmentioning

confidence: 98%

Molecular Detection of the VirulentExoUGenotype ofPseudomonas aeruginosaIsolated from Infected Surgical Incisions

Hassuna

2016

Surgical Infections

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“…8,9 Ancak bu çalışmadaki hastaların kolistin kullanım sü-resi 14 günden az tutulmuştur. 10 Normal kilolu hastalarda ise %15'ten daha az tespit edilmiştir. Kolistin kullanımının kilodan bağımsız olarak dört haftayı geçmesi durumunda nefrotoksisite kaçınılmaz olmaktadır.…”

Section: Discussionunclassified

“…10 Bu araştırmanın retrospektif bir çalışma olması, kesin bir karara varabilmek için örneklem bü-yüklüğünün yeterli olmadığını düşündürmektedir. Ancak, bizim sonuçlarımıza baktığımızda, kolistin kullanım süresi 12 günün üzerinde olan hastalarımı-zın hepsinde nefrotoksisite gelişmiş ve diyaliz uygulanmıştır.…”

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Evaluation of the Use of Colistin on Nephrotoxicity and Mortality in the Intensive Care Unit

Arslan¹,

Özbudak²,

Türkyılmaz³

et al. 2015

Turkiye Klinikleri J Anest Reanim

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Ö ÖZ ZE ET T A Am ma aç ç: : Kolistin, siklik yapılı katyonik polipeptidlerin bir üyesidir. Son yıllarda çoklu ilaç dirençli Pseudomonas aeruginosa ve Acinetobacter baumannii enfeksiyonlarında tek seçenek olan kolistinin nefrotoksik etkisi en önemli dezavantajıdır. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Etik kurul onayı alındıktan sonra, Ocak 2012-Aralık 2013 tarihleri arasında yoğun bakım ünitesinde yatan ve çoklu ilaç dirençli gram-negatif enfeksiyon geliş-mesi nedeni ile beş günden daha fazla intravenöz 3-5 mg/kg kolistin kullanmış hastalar bu çalışmaya dâhil edildi. Yatışında böbrek fonksiyon bozukluğu saptanan hastalar çalışma dışı bırakıldı. Hastalar akut böbrek hasarı gelişen ve gelişmeyenler olarak iki gruba ayrıldı. B Bu ul lg gu ul la ar r: : İki yıl süresince, yoğun bakım ünitesinde 48 hastanın beş günden daha fazla kolistin kullandığı ve bu hastalardan beşinin geldiklerinde kronik böbrek yetersizliği olduğu tespit edildi. Kalan 43 hastanın 15 (%35)'inde akut böbrek hasarı geliştiği saptandı. Bu iki grup arasında kabulleri esnasındaki yaş, cinsiyet, APACHE II skorları, sedimentasyon ve C-reaktif protein dü-zeyleri, üreyen patojen ve üreme yerleri, ek nefrotoksik ilaç kullanımı açısından fark saptanmadı. Hastaların hepsinin mekanik ventilatöre bağlı olduğu, kolistin başlama endikasyonunun ise çoklu ilaç dirençli P. aeruginasa ve A. baumannii enfeksiyonuna bağlı ventilatörle ilişkili pnömoni olduğu saptandı. Akut böbrek hasarı gelişen grupta kolistin kullanım süresi uzundu (11,8±7,3 ve 17,7±14,3 gün; p=0,009). Akut böbrek hasarı gelişen grubun yoğun bakım ünitesinde yatış süreleri daha uzun (30±18,1 ve 46,1±29,1; p=0,04) ve mortalite oranı daha yüksekti (%80 vs %36; p=0,006). Akut böbrek hasarı gelişen grubun hepsi inotrop kullanmıştır (p<0,001). S So on nu uç ç: : Kolistin nefrotoksisitesi, kullanım süresi ile ilişkili görünmektedir. Kolistinle indüklenen nefrotoksisite gelişen hastalarda yoğun bakım ünitesinde kalış süresi uzamakta ve mortalite artmaktadır. Bu konuda yapılacak çok-merkezli çalışmalara ihtiyaç vardır.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Kolistin; ölüm oranı; yoğun bakım; akut böbrek hasarı A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Colistin is the member of the cyclic structured cationic polypeptides. In the recent years, colistin is the only choice for the multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii infections but its nephrotoxicity is the most important disadvantage. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : After research ethics committee approval, patients who had stayed in the intensive care unit more than five days and used intravenous colistin 3-5 mg/kg for multiple drug resistant gram-negative infection between January 2012 and December 2013 were enrolled in this retrospective study. Patients who had known renal function disorder before the intensive care unit acceptance were excluded from the analysis of this study. Patients were divided into two groups as; acute kidney injury develop...

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“…The two major components of the mixture are colistin A (polymyxin E1) and colistin B (polymyxin E2) [4]. Colistin A and B have a discrete neuro-and nephrotoxicity [5][6][7][8]. To reduce colistine nephro-and neurotoxicity, the drug is currently administered intravenously as sodium colistimethate (CMS), an inactive prodrug which is hydrolyzed in vivo to the active colistin base moiety [2][3][4].…”

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confidence: 99%

Efficient removal of colistin A and B in critically ill patients undergoing CVVHDF and sorbent technologies

et al. 2014

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Background Colistin pharmacokinetics data are scarce regarding patients undergoing renal replacement therapy (RRT), or even absent as in patients treated with sorbent technologies potentially capable of removing colistin by extensive absorption on many polymeric materials.Methods Twelve septic shock patients with acute kidney injury (AKI) undergoing RRT [continuous venovenous hemodiafiltration (CVVHDF) n = 7, coupled-plasma filtration adsorption-HF (CPFA-HF) n = 4, hemoperfusion n = 1] treated with colistin methanesulfonate at a dose of 4.5 9 106 U bid were studied. Colistin A (Col-A) and colistin B (Col-B) concentrations on plasma and effluent at time 0, 0.2, 1, 3, 6, 12, 24 and 48 h were determined by the liquid chromatography-tandem mass spectrometry method.Results With CVVHDF the sieving coefficient was lower for Col-A, peaked early (0.40 for Col-A at 10 min, and 0.59 for Col-B at 3 h) and declined after 48 h (0.22 and 0.30 for Col-A and Col-B, respectively). Colistin's filter clearance showed a similar pattern, with the highest clearance value of 18.7 ml/min for Col-B at 1 h. With CPFA-HF after the cartridge the Col-A and Col-B levels were negligible (\0.2 mg/l) or not detectable. The sum of the effluent and cartridge clearances reached values of 30 and 40 ml/min for Col-A and Col-B, respectively. With hemoperfusion the postcartridge concentrations for Col-A and Col-B were about 30 % lower than those determined precartridge. Conclusions During CPFA-HF and CVVHDF, the extent of colistin removal is high, and patients should receive an unreduced dosage. However, due to risk of accumulation in longterm administration colistin plasma levels determination is recommended. Key WordsColistin sieving coefficient _ Colistin extracorporeal removal _ CVVHDF _ Coupled plasmafiltration adsorption _ Hemoperfusion Introduction Colistin (polymyxin E), a re-emerged antibiotic for multidrug-resistant gram-negative bacterial infections [1][2][3][4], is an antibiotic mixture containing more than 30 components differing in aminoacid and fatty-acid residue composition. The two major components of the mixture are colistin A (polymyxin E1) and colistin B (polymyxin E2) [4]. Colistin A and B have a discrete neuro-and nephrotoxicity [5][6][7][8]. To reduce colistine nephro-and neurotoxicity, the drug is currently administered intravenously as sodium colistimethate (CMS), an inactive prodrug which is hydrolyzed in vivo to the active colistin base moiety [2][3][4]. The risk of colistin nephrotoxicity proved to be clinically significant after 14 days administration [5]; it appeared to be linked to its cumulative dosage [6], was associated with advancing age and receipt of concurrent nephrotoxic agents [7], and was predicted by the plasma colistin level [8].Pharmacokinetics and pharmacodynamics of colistin are complex, and data are relatively scarce for critically ill patients with acute kidney injury (AKI) undergoing continuous venovenous hemodiafiltration (CVVHDF) or hemodialysis, which provide inconstant clearance of colistin i...

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Nephrotoxicity Associated with Intravenous Colistin (Colistimethate Sodium) Treatment at a Tertiary Care Medical Center

Cited by 327 publications

References 19 publications

Molecular Detection of the VirulentExoUGenotype ofPseudomonas aeruginosaIsolated from Infected Surgical Incisions

Molecular Detection of the VirulentExoUGenotype ofPseudomonas aeruginosaIsolated from Infected Surgical Incisions

Evaluation of the Use of Colistin on Nephrotoxicity and Mortality in the Intensive Care Unit

Efficient removal of colistin A and B in critically ill patients undergoing CVVHDF and sorbent technologies

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