Passage of Chloramphenicol and Sodium Colistimethate Into the Cerebrospinal Fluid

Wynne, J M

doi:10.1001/archpedi.1966.02090140094007

Cited by 15 publications

(7 citation statements)

References 6 publications

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“…In these patients, the contribution of intravenous CMS to the concentration of colistin in the CSF is unknown. However, it has been reported that the plasma concentration of colistin is 2 to 3 g/ml (7,17,22,25), and on the basis of currently available data in humans (1,11,21,30), it is reasonable to expect that diffusion or active transport (active transport has been excluded in an animal model [12]) of colistin across the blood-CSF barrier made a very small contribution to the levels of colistin in the CSF.…”

Section: Discussionmentioning

confidence: 99%

“…CMS, which is inactive, is converted to colistin (the active form with antimicrobial activity) both in vitro and in vivo by hydrolysis of methanesulfonate radicals (2,4). Data available from the literature indicate that in humans, the penetration of CMS and colistin into cerebrospinal fluid (CSF) is poor, both in patients with uninflamed and those with inflamed meninges (1,11,21,30). Reported CSF-to-serum concentration ratios are 0.051 to 0.057 (21) and 0.16 (estimated from the data shown in Fig.…”

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confidence: 99%

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Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

Imberti

Cusato

Accetta

et al. 2012

Antimicrob Agents Chemother

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f Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ؎ standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t 1/2 ) were 0.033 ؎ 0.014 liter/h and 7.8 ؎ 3.2 h, respectively, and the average time to the peak concentration was 3.7 ؎ 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of >5.22 mg/ day, measured CSF concentrations of colistin were continuously above the MIC of 2 g/ml, and measured values of trough concentration (C trough ) ranged between 2.0 and 9.7 g/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of >5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

Imberti

Cusato

Accetta

et al. 2012

Antimicrob Agents Chemother

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“…Relevant data are also provided from older studies focusing on systemic colistin in the treatment of infections in children with burns [72], perforative appendicitis and periappendicular abscesses [73], and infections in hydrocephalic children [74]. In contrast, a study reporting the use of i.m.…”

Section: Discussionmentioning

confidence: 99%

Systemic colistin use in children without cystic fibrosis: a systematic review of the literature

Falagas

Vouloumanou

Rafailidis

2009

International Journal of Antimicrobial Agents

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“…Therefore, bioassay results will be misleading, since some of the colistimethate present in the biological fluid will be converted to colistin during the incubation period. In addition, some studies have used colistimethate for the preparation of the control concentrations in the bioassay, adding another source of error (52,185). Therefore, those studies should be interpreted with caution and serve only as a rough estimate for pharmacokinetic analysis.…”

Section: Serum Concentrationsmentioning

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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Passage of Chloramphenicol and Sodium Colistimethate Into the Cerebrospinal Fluid

Cited by 15 publications

References 6 publications

Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

Systemic colistin use in children without cystic fibrosis: a systematic review of the literature

Polymyxins Revisited

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