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Colistin is an antibiotic drug that is used to treat various bacterial infections, particularly those caused by multidrug-resistant bacteria. It is often used a...
Colistin is an antibiotic drug that is used to treat various bacterial infections, particularly those caused by multidrug-resistant bacteria. It is often used as a last resort when other antibiotics are ineffective. Colistin works by disrupting the outer membrane of the bacterial cell, ultimately leading to its death. However, colistin is known to have potential side effects and toxicity, and therefore is typically reserved for serious infections when other treatment options have failed.
Certainly! Colistin is a type of antibiotic that falls into the category of polymyxin antibiotics. It is effective against a wide variety of bacteria, including some strains that have developed resistance to other antibiotics. Colistin is primarily used to treat infections caused by Gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. These bacteria are often associated with hospital-acquired infections and can be particularly challenging to treat due to their resistance to multiple antibiotics.
Colistin is available in various forms, including oral and intravenous formulations. When administered intravenously, it is typically given in a hospital setting under the supervision of healthcare professionals.
As mentioned earlier, colistin can have potential side effects, such as kidney damage and nerve damage, especially when used in high doses or for prolonged periods. Therefore, its use is carefully monitored, and the benefits of using colistin must be weighed against the potential risks.
Given the rise of antibiotic-resistant bacteria, colistin has seen renewed use in certain cases, particularly as a "last-resort" treatment for serious infections that do not respond to other antibiotics. However, its use is carefully controlled to minimize the risk of resistance and adverse effects.
Colistin is also known as polymyxin E and has been used for decades in clinical practice, but its use declined with the development of newer antibiotics due to concerns about its potential toxicity. However, the emergence of multidrug-resistant bacteria, particularly in healthcare settings, has led to a resurgence in the use of colistin as a treatment option.
It's important to note that the use of colistin requires careful consideration and should be guided by antimicrobial stewardship programs to ensure appropriate and responsible use. This is particularly important to prevent the development and spread of further antibiotic resistance.
In some cases, colistin may be used in combination with other antibiotics to enhance its effectiveness and reduce the risk of resistance. Research into the optimal use of colistin, including dosing regimens and combination therapies, is ongoing to improve treatment outcomes and minimize adverse effects.
Furthermore, ongoing surveillance of colistin resistance among bacteria is crucial to monitor and address any emerging resistance patterns. Effective infection control measures in healthcare settings also play a critical role in reducing the spread of resistant bacteria and limiting the need for antibiotics such as colistin.
Colistin Resistance in <i>Acinetobacter baumannii</i> Is Mediated by Complete Loss of Lipopolysaccharide Production Antimicrobial Agents and Chemotherapy - Tập 54 Số 12 - Trang 4971-4977 - 2010
ABSTRACT
Infections caused by multidrug-resistant (MDR) Gram-negative bacteria represent a major global health problem. Polymyxin antibiotics such as colistin have resurfaced as effective last-resort antimicrobials for use against MDR Gram-negative pathogens, including
Acinetobacter baumannii
. Here we show that
A. baumannii
can rapidly develop resistance to polymyxin antibiotics by complete loss of the initial binding target, the lipid A component of lipopolysaccharide (LPS), which has long been considered to be essential for the viability of Gram-negative bacteria. We characterized 13 independent colistin-resistant derivatives of
A. baumannii
type strain ATCC 19606 and showed that all contained mutations within one of the first three genes of the lipid A biosynthesis pathway:
lpxA
,
lpxC
, and
lpxD
. All of these mutations resulted in the complete loss of LPS production. Furthermore, we showed that loss of LPS occurs in a colistin-resistant clinical isolate of
A. baumannii
. This is the first report of a spontaneously occurring, lipopolysaccharide-deficient, Gram-negative bacterium.
Population Pharmacokinetics of Colistin Methanesulfonate and Formed Colistin in Critically Ill Patients from a Multicenter Study Provide Dosing Suggestions for Various Categories of Patients Antimicrobial Agents and Chemotherapy - Tập 55 Số 7 - Trang 3284-3294 - 2011
ABSTRACT
With increasing clinical emergence of multidrug-resistant Gram-negative pathogens and the paucity of new agents to combat these infections, colistin (administered as its inactive prodrug colistin methanesulfonate [CMS]) has reemerged as a treatment option, especially for critically ill patients. There has been a dearth of pharmacokinetic (PK) data available to guide dosing in critically ill patients, including those on renal replacement therapy. In an ongoing study to develop a population PK model for CMS and colistin, 105 patients have been studied to date; these included 12 patients on hemodialysis and 4 on continuous renal replacement therapy. For patients not on renal replacement, there was a wide variance in creatinine clearance, ranging from 3 to 169 ml/min/1.73 m
2
. Each patient was treated with a physician-selected CMS dosage regimen, and 8 blood samples for PK analysis were collected across a dosage interval on day 3 or 4 of therapy. A linear PK model with two compartments for CMS and one compartment for formed colistin best described the data. Covariates included creatinine clearance on the total clearance of CMS and colistin, as well as body weight on the central volume of CMS. Model-fitted parameter estimates were used to derive suggested loading and maintenance dosing regimens for various categories of patients, including those on hemodialysis and continuous renal replacement. Based on our current understanding of colistin PK and pharmacodynamic relationships, colistin may best be used as part of a highly active combination, especially for patients with moderate to good renal function and/or for organisms with MICs of ≥1.0 mg/liter.
Heteroresistance to Colistin in Multidrug-Resistant <i>Acinetobacter baumannii</i> Antimicrobial Agents and Chemotherapy - Tập 50 Số 9 - Trang 2946-2950 - 2006
ABSTRACT
Multidrug-resistant
Acinetobacter baumannii
has emerged as a significant clinical problem worldwide and colistin is being used increasingly as “salvage” therapy. MICs of colistin against
A. baumannii
indicate its significant activity. However, resistance to colistin in
A. baumannii
has been reported recently. Clonotypes of 16 clinical
A. baumannii
isolates and ATCC 19606 were determined by pulsed-field gel electrophoresis (PFGE), and colistin MICs were measured. The time-kill kinetics of colistin against
A. baumannii
ATCC 19606 and clinical isolate 6 were investigated, and population analysis profiles (PAPs) were conducted. Resistance development was investigated by serial passaging with or without exposure to colistin. Five different PFGE banding patterns were found in the clinical isolates. MICs of colistin against all isolates were within 0.25 to 2 μg/ml. Colistin showed early concentration-dependent killing, but bacterial regrowth was observed at 24 h. PAPs revealed that heteroresistance to colistin occurred in 15 of the 16 clinical isolates. Subpopulations (<0.1% from inocula of 10
8
to 10
9
CFU/ml) of ATCC 19606, and most clinical isolates grew in the presence of colistin 3 to 10 μg/ml. Four successive passages of ATCC 19606 in broth containing colistin (up to 200 μg/ml) substantially increased the proportion of the resistant subpopulations able to grow in the presence of colistin at 10 μg/ml from 0.000023 to 100%; even after 16 passages in colistin-free broth, the proportion only decreased to 2.1%. This represents the first demonstration of heterogeneous colistin-resistant
A. baumannii
in “colistin-susceptible” clinical isolates. Our findings give a strong warning that colistin-resistant
A. baumannii
may be observed more frequently due to potential suboptimal dosage regimens recommended in the product information of some products of colistin methanesulfonate.
Multiplex PCR for detection of plasmid-mediated colistin resistance determinants, mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 for surveillance purposes Eurosurveillance - Tập 23 Số 6 - 2018
Background and aim
Plasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (mcr-1 to mcr-5, and variants) in Enterobacteriaceae was developed for surveillance or research purposes. Methods: We designed four new primer pairs to amplify mcr-1, mcr-2, mcr-3 and mcr-4 gene products and used the originally described primers for mcr-5 to obtain a stepwise separation of ca 200 bp between amplicons. The primer pairs and amplification conditions allow for single or multiple detection of all currently described mcr genes and their variants present in Enterobacteriaceae. The protocol was validated testing 49 European Escherichia coli and Salmonella isolates of animal origin. Results: Multiplex PCR results in bovine and porcine isolates from Spain, Germany, France and Italy showed full concordance with whole genome sequence data. The method was able to detect mcr-1, mcr-3 and mcr-4 as singletons or in different combinations as they were present in the test isolates. One new mcr-4 variant, mcr-4.6**, was also identified. Conclusions: This method allows rapid identification of mcr-positive bacteria and overcomes the challenges of phenotypic detection of colistin resistance. The multiplex PCR should be particularly interesting in settings or laboratories with limited resources for performing genetic analysis as it provides information on the mechanism of colistin resistance without requiring genome sequencing.
The global distribution and spread of the mobilized colistin resistance gene mcr-1 Nature Communications - Tập 9 Số 1
AbstractColistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae. As such, the recent plasmid-mediated spread of the colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Here, we characterize the global distribution of mcr-1 using a data set of 457 mcr-1-positive sequenced isolates. We find mcr-1 in various plasmid types but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002–2008; 95% highest posterior density), followed by a marked demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of antibiotic resistance genes across multiple levels of genomic organization.
Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by Gram-Negative Bacteria Antimicrobial Agents and Chemotherapy - Tập 53 Số 8 - Trang 3430-3436 - 2009
ABSTRACT
Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.
