Kolistimetatnatrium Xellia (Colistimethate Sodium)
Polymyxin antibiotic for multidrug-resistant Gram-negative infections
Kolistimetatnatrium Xellia (colistimethate sodium) is a last-resort intravenous antibiotic belonging to the polymyxin class. It is used to treat serious, life-threatening infections caused by multidrug-resistant (MDR) Gram-negative bacteria, particularly Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacterales. Due to significant risks of nephrotoxicity and neurotoxicity, colistimethate sodium is reserved exclusively for situations where no other effective antibiotics are available. Treatment requires close monitoring in a hospital setting.
Quick Facts
Key Takeaways
- Kolistimetatnatrium Xellia is a last-resort antibiotic used only when other antibiotics have failed against multidrug-resistant Gram-negative bacteria.
- Nephrotoxicity (kidney damage) is the most common serious side effect, occurring in 20–60% of patients, and requires careful renal monitoring every 48 hours.
- The drug is administered as an intravenous infusion in hospital settings only, with dosing adjusted based on body weight and kidney function.
- Colistimethate sodium is classified by the WHO as a critically important antimicrobial that must be preserved for human medicine.
- A loading dose is recommended to rapidly achieve effective plasma concentrations, followed by maintenance dosing divided into 2–3 daily infusions.
What Is Kolistimetatnatrium Xellia and What Is It Used For?
Kolistimetatnatrium Xellia is a formulation of colistimethate sodium (also known as colistin methanesulfonate sodium, or CMS), manufactured by Xellia Pharmaceuticals. Colistimethate sodium is an inactive prodrug that converts to the active antimicrobial agent colistin (polymyxin E) after administration. Colistin belongs to the polymyxin class of antibiotics, a group of cyclic polypeptide antibiotics that were first discovered in the 1940s and introduced into clinical use in the late 1950s.
The drug works by binding to lipopolysaccharides (LPS) and phospholipids in the outer membrane of Gram-negative bacteria. This binding disrupts the structural integrity of the bacterial cell membrane, leading to increased permeability, leakage of intracellular contents, and ultimately bacterial cell death through osmotic lysis. This mechanism of action is distinct from most other antibiotic classes, which is why colistin often remains effective against bacteria that have developed resistance to multiple other drug classes.
Colistin was widely used in clinical practice during the 1960s and 1970s but was largely abandoned due to reports of significant nephrotoxicity (kidney damage) and neurotoxicity. However, the alarming global rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative infections, particularly those resistant to carbapenems (often considered the last line of conventional antibiotics), forced clinicians to re-evaluate colistin as a therapeutic option. Today, colistimethate sodium has been reintroduced as a critical last-resort therapy in intensive care units and specialised infectious disease departments worldwide.
Indications
Kolistimetatnatrium Xellia is indicated for the treatment of serious infections caused by susceptible Gram-negative organisms in patients with limited treatment options. The primary clinical indications include:
- Ventilator-associated pneumonia (VAP) caused by MDR Pseudomonas aeruginosa or Acinetobacter baumannii
- Hospital-acquired pneumonia (HAP) due to carbapenem-resistant organisms
- Bloodstream infections (bacteraemia) caused by XDR Gram-negative bacteria
- Urinary tract infections caused by MDR Gram-negative pathogens
- Intra-abdominal infections when no alternative agents are effective
- Central nervous system infections (via intrathecal or intraventricular route in exceptional cases)
- Cystic fibrosis-related respiratory infections caused by Pseudomonas aeruginosa (via nebulisation)
The World Health Organization (WHO) classifies polymyxins as Highest Priority Critically Important Antimicrobials, emphasising the necessity of preserving their effectiveness through responsible antimicrobial stewardship. The European Medicines Agency (EMA) and the Infectious Diseases Society of America (IDSA) recommend that colistimethate sodium be used only when susceptibility testing confirms the pathogen is resistant to all other available antibiotics.
What Should You Know Before Taking Kolistimetatnatrium Xellia?
Contraindications
Kolistimetatnatrium Xellia must not be used in patients with:
- Known hypersensitivity to colistimethate sodium, colistin, or other polymyxin antibiotics (polymyxin B)
- Myasthenia gravis — colistin can exacerbate neuromuscular blockade and may cause respiratory failure in these patients
While severe renal impairment is not an absolute contraindication, it requires extremely careful dose adjustment and intensive monitoring. The decision to treat must weigh the severity of the infection against the risk of further kidney damage.
Warnings and Precautions
Nephrotoxicity is the most significant risk of colistimethate sodium therapy. Acute kidney injury has been reported in 20–60% of treated patients, depending on dose, duration, and concomitant nephrotoxic medications. Renal function must be assessed before treatment and monitored at least every 48 hours during therapy.
Healthcare providers must exercise particular caution in the following situations:
- Pre-existing renal impairment: Patients with reduced kidney function are at significantly higher risk of nephrotoxicity. Dose reduction and extended dosing intervals are mandatory, guided by creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR).
- Neurotoxicity: Colistin can cause neurological adverse effects including paraesthesia (tingling or numbness), dizziness, visual disturbances, vertigo, confusion, slurred speech, and in rare cases, neuromuscular blockade leading to respiratory muscle weakness. Patients should be monitored for neurological symptoms throughout treatment.
- Concurrent nephrotoxic drugs: The concomitant use of other nephrotoxic agents (aminoglycosides, vancomycin, amphotericin B, NSAIDs, contrast media) significantly increases the risk of kidney damage. These combinations should be avoided when possible or closely monitored.
- Neuromuscular blocking agents: Co-administration with non-depolarising muscle relaxants (e.g., tubocurarine, pancuronium) or other neuromuscular blocking agents should be undertaken with extreme caution, as colistin can potentiate neuromuscular blockade.
- Elderly patients: Older adults are more susceptible to both nephrotoxicity and neurotoxicity due to age-related decline in renal function. Careful dose adjustment based on actual renal function is essential.
- Hydration status: Adequate hydration before and during treatment helps reduce the risk of nephrotoxicity. Dehydration significantly increases the risk of acute kidney injury.
Pregnancy and Breastfeeding
There is limited clinical data on the use of colistimethate sodium during pregnancy. Animal reproductive studies have shown that colistin can cross the placental barrier and may have adverse effects on foetal development. Therefore, Kolistimetatnatrium Xellia should only be used during pregnancy if the potential benefit to the mother clearly outweighs the potential risk to the foetus, and only when no safer alternative antibiotics are available.
Colistin is excreted in breast milk. Due to the potential for serious adverse effects in nursing infants, including nephrotoxicity and neurotoxicity, breastfeeding should be discontinued during treatment with colistimethate sodium. Mothers who wish to resume breastfeeding should consult their healthcare provider regarding the appropriate waiting period after the last dose.
Therapeutic drug monitoring (TDM) of colistin plasma concentrations is recommended where available, particularly in critically ill patients, those with renal impairment, and obese patients. Target steady-state plasma colistin concentrations of 2–4 mg/L are associated with optimal efficacy while minimising toxicity risk.
How Does Kolistimetatnatrium Xellia Interact with Other Drugs?
Drug interactions with colistimethate sodium are primarily pharmacodynamic in nature, meaning they relate to additive or synergistic toxicity rather than changes in drug metabolism. The most important interactions involve drugs that share colistin's nephrotoxic or neurotoxic profiles.
Major Interactions
| Interacting Drug | Risk | Clinical Action |
|---|---|---|
| Aminoglycosides (gentamicin, tobramycin, amikacin) | Additive nephrotoxicity and neurotoxicity | Avoid combination if possible; if essential, monitor renal function daily and check drug levels |
| Vancomycin | Increased nephrotoxicity risk | Monitor renal function at least every 24–48 hours; ensure adequate hydration |
| Amphotericin B | Severe additive nephrotoxicity | Avoid concurrent use whenever possible; consider liposomal formulations if antifungal therapy required |
| Non-depolarising muscle relaxants (tubocurarine, pancuronium, vecuronium) | Potentiation of neuromuscular blockade; risk of respiratory paralysis | Use with extreme caution; monitor respiratory function closely; have reversal agents available |
| Loop diuretics (furosemide, bumetanide) | Increased nephrotoxicity due to volume depletion and direct renal effects | Monitor fluid balance, electrolytes, and renal function closely |
Minor Interactions
| Interacting Drug | Risk | Clinical Action |
|---|---|---|
| NSAIDs (ibuprofen, diclofenac) | Potential additive nephrotoxicity | Avoid if possible; monitor renal function |
| Ciclosporin / Tacrolimus | Additive nephrotoxicity | Monitor drug levels and renal function closely |
| IV contrast media | Additive renal toxicity | Ensure adequate hydration; space administration if possible |
It is essential that the treating physician reviews the complete medication list of any patient being considered for colistimethate sodium therapy. Pharmacokinetic interactions are minimal, as colistimethate sodium is not metabolised by cytochrome P450 enzymes and is primarily eliminated renally. However, any drug that affects renal function can indirectly influence colistin clearance and toxicity risk.
What Is the Correct Dosage of Kolistimetatnatrium Xellia?
Colistimethate sodium dosing varies significantly between products and between International Units (IU) and milligrams of colistin base activity (CBA). Always verify the specific product label and dosing units. Dosing errors due to unit confusion have caused serious harm. 1 million IU of CMS ≈ 80 mg CMS ≈ 33.3 mg colistin base activity (CBA).
Adults
Standard Adult Dosage (Normal Renal Function)
Loading dose: 9 million IU (approximately 300 mg CBA), administered as a single intravenous infusion over 30–60 minutes.
Maintenance dose: 9 million IU per day, divided into 2–3 equal doses (i.e., 3–4.5 million IU every 8–12 hours), administered as intravenous infusions each over 30–60 minutes.
Duration: Treatment duration depends on the type and severity of infection and clinical response, typically ranging from 7 to 14 days.
| Creatinine Clearance (mL/min) | Daily Maintenance Dose | Dosing Interval |
|---|---|---|
| > 50 mL/min (normal/mild impairment) | 9 million IU/day | Every 8 hours (3 divided doses) |
| 30–50 mL/min (moderate impairment) | 5.5–7.5 million IU/day | Every 12 hours |
| 10–29 mL/min (severe impairment) | 4.5–5.5 million IU/day | Every 12–24 hours |
| < 10 mL/min (end-stage renal disease) | 3.5 million IU/day | Every 24 hours |
| Haemodialysis patients | Supplemental dose after each dialysis session | Consult specialist |
Children
Paediatric Dosage
For children weighing ≤ 40 kg, the recommended dose is 75,000–150,000 IU/kg/day, divided into 3 doses.
For children weighing > 40 kg, adult dosing guidelines apply.
Paediatric dosing should be determined by a specialist in paediatric infectious diseases. Renal function monitoring is equally important in children.
Elderly
Elderly Patients (≥ 65 years)
No specific dose adjustments based on age alone, but elderly patients frequently have reduced renal function that may not be reflected by serum creatinine alone. Dosing should be guided by estimated creatinine clearance (using the Cockcroft-Gault formula) or eGFR. More frequent renal monitoring (every 24–48 hours) is recommended in this population.
Missed Dose
As colistimethate sodium is administered in a hospital setting under medical supervision, missed doses are uncommon. If a dose is delayed, it should be administered as soon as possible without doubling the next dose. The treating physician should adjust the dosing schedule to maintain appropriate plasma concentrations. Consistent dosing is important to maintain bactericidal activity and prevent the emergence of resistance.
Overdose
Overdose of colistimethate sodium can cause acute kidney injury, neuromuscular blockade, respiratory failure, and neurological symptoms including muscle weakness, apnoea, and altered consciousness. There is no specific antidote for colistin overdose. Management is supportive and may include:
- Immediate cessation of colistimethate sodium therapy
- Aggressive intravenous hydration to support renal function
- Respiratory support, including mechanical ventilation if neuromuscular blockade occurs
- Haemodialysis — colistimethate sodium is partially removed by haemodialysis, which may be beneficial in severe overdose
- Monitoring of renal function, electrolytes, and neurological status in an intensive care setting
What Are the Side Effects of Kolistimetatnatrium Xellia?
Like all medicines, colistimethate sodium can cause side effects, although not everybody gets them. The side effect profile of colistin is dominated by its effects on the kidneys and nervous system. The frequency and severity of adverse effects are influenced by total daily dose, duration of treatment, pre-existing renal function, and concomitant use of other nephrotoxic or neurotoxic agents.
Very Common (may affect more than 1 in 10 patients)
- Nephrotoxicity (increased serum creatinine, reduced creatinine clearance, acute kidney injury)
- Paraesthesia (tingling, numbness, or prickling sensation, particularly in the face and extremities)
Common (may affect up to 1 in 10 patients)
- Dizziness and vertigo
- Nausea and vomiting
- Headache
- Electrolyte disturbances (hypokalaemia, hypomagnesaemia)
- Rash or pruritus (itching)
- Diarrhoea
Uncommon (may affect up to 1 in 100 patients)
- Neuromuscular blockade (muscle weakness)
- Visual disturbances (blurred vision)
- Slurred speech
- Confusion or psychosis
- Hypotension
- Bronchospasm (particularly with nebulised administration)
Rare (may affect fewer than 1 in 1,000 patients)
- Respiratory failure secondary to neuromuscular blockade
- Anaphylaxis or severe hypersensitivity reactions
- Seizures
- Ataxia (loss of coordination)
- Renal failure requiring dialysis
Colistin-induced nephrotoxicity is dose-dependent and typically develops within the first 5–7 days of treatment. Risk factors include high total daily dose, prolonged treatment duration, concomitant nephrotoxic drugs, hypoalbuminaemia, critical illness severity, and pre-existing renal impairment. In many cases, kidney function recovers partially or completely after discontinuation of the drug. Maintaining adequate hydration and avoiding concurrent nephrotoxins are key protective strategies. The use of extended-infusion protocols and therapeutic drug monitoring may help reduce nephrotoxicity risk.
If you experience any side effects, particularly signs of kidney problems (reduced urine output, dark urine, swelling) or neurological symptoms (significant weakness, difficulty breathing, severe dizziness), your medical team should be informed immediately. In a hospital setting, these parameters are continuously monitored.
How Should You Store Kolistimetatnatrium Xellia?
Proper storage of Kolistimetatnatrium Xellia is essential to maintain the drug's stability and efficacy:
- Unopened vials: Store below 25°C (77°F). Keep the vials in the original outer carton to protect from light. Do not freeze.
- After reconstitution: The reconstituted solution should ideally be used immediately. If not used immediately, chemical and physical in-use stability has been demonstrated for up to 24 hours at 2–8°C (refrigerated). From a microbiological point of view, the product should be used immediately upon reconstitution.
- Do not use this medicine after the expiry date printed on the vial and outer packaging. The expiry date refers to the last day of that month.
- Do not use if the reconstituted solution appears cloudy, contains visible particles, or shows any discolouration.
- Keep out of the sight and reach of children.
- Do not dispose of medicines via household waste or wastewater. Ask your pharmacist about how to dispose of medicines no longer needed, in accordance with local regulations.
In hospital settings, storage and handling of colistimethate sodium are managed by the pharmacy department in accordance with Good Distribution Practice (GDP) and local infection control protocols. Healthcare professionals should follow standard aseptic technique when reconstituting and preparing the infusion solution.
What Does Kolistimetatnatrium Xellia Contain?
Active substance: Colistimethate sodium (colistin methanesulfonate sodium). Each vial contains colistimethate sodium equivalent to 3 million IU (approximately 240 mg of colistimethate sodium, equivalent to approximately 100 mg of colistin base activity).
Excipients: This product does not contain additional excipients. The powder for solution for infusion consists solely of the active substance, colistimethate sodium.
Appearance: White to slightly yellowish lyophilised powder or cake in a clear glass vial, sealed with a rubber stopper and aluminium cap. After reconstitution with the appropriate diluent (typically 0.9% sodium chloride or 5% dextrose), the solution should be clear and colourless to slightly yellow.
Reconstitution: The powder must be reconstituted with a suitable sterile diluent before intravenous administration. The reconstituted solution is then further diluted in an appropriate volume of compatible infusion fluid (typically 0.9% sodium chloride solution) for intravenous infusion over 30–60 minutes. Detailed reconstitution and dilution instructions are provided in the Summary of Product Characteristics and should be followed precisely by qualified healthcare professionals.
Frequently Asked Questions
Kolistimetatnatrium Xellia (colistimethate sodium) is a last-resort intravenous antibiotic used to treat serious infections caused by multidrug-resistant (MDR) Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem-resistant Enterobacterales. It is used only in hospital settings when no other effective antibiotics are available, typically for ventilator-associated pneumonia, bloodstream infections, and urinary tract infections caused by these resistant organisms.
Colistimethate sodium is supplied as a powder (3 million IU per vial) that must be reconstituted and administered as an intravenous infusion over 30 to 60 minutes. A loading dose of 9 million IU is typically given first, followed by maintenance doses of 9 million IU per day divided into 2–3 separate infusions. In some cases, it can also be administered via nebulisation for respiratory infections. It is always prepared and given in a hospital under close medical supervision.
The two most serious side effects are nephrotoxicity (kidney damage) and neurotoxicity. Kidney injury occurs in approximately 20–60% of patients and is usually dose-dependent and reversible if detected early and the drug is discontinued or the dose reduced. Neurotoxic effects can include paraesthesia (tingling and numbness), dizziness, visual disturbances, confusion, and in rare cases, neuromuscular blockade that can cause respiratory failure. Renal function must be monitored at least every 48 hours during treatment.
Colistin (polymyxin E) was largely abandoned in the 1970s due to its significant nephrotoxicity and neurotoxicity. It was reintroduced as a last-resort therapy because of the global emergence of multidrug-resistant and extensively drug-resistant Gram-negative infections, particularly those resistant to carbapenems. When bacteria are resistant to all other available antibiotics, colistin often remains effective because its unique mechanism of action (disrupting bacterial cell membranes) is different from all other antibiotic classes. The WHO classifies polymyxins as Highest Priority Critically Important Antimicrobials.
There is very limited clinical data on the safety of colistimethate sodium during pregnancy. Animal studies suggest potential reproductive toxicity, as colistin can cross the placental barrier. It should only be used during pregnancy if the infection is life-threatening and no safer alternatives exist. The potential benefit to the mother must clearly outweigh the potential risk to the foetus. Breastfeeding should be discontinued during treatment, as colistin is excreted in breast milk and could harm the nursing infant.
Renal function should be assessed before starting treatment and monitored at least every 48 hours during therapy using serum creatinine and estimated glomerular filtration rate (eGFR). In high-risk patients or those on concurrent nephrotoxic drugs, daily monitoring may be warranted. If significant deterioration in kidney function is detected, the dose should be reduced or treatment temporarily paused. Adequate hydration is an important protective measure. Where available, therapeutic drug monitoring (TDM) of colistin plasma levels (target 2–4 mg/L) can help optimise dosing.
References
This article is based on the following peer-reviewed sources and international guidelines:
- Nation RL, Li J, Cars O, et al. Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus. Lancet Infectious Diseases. 2015;15(2):225-234. doi:10.1016/S1473-3099(14)70850-3
- European Medicines Agency (EMA). Updated review of polymyxin-based medicines. EMA/CVMP/PhVWP. 2015. Available at: ema.europa.eu
- Tsuji BT, Pogue JM, Zavascki AP, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins. Pharmacotherapy. 2019;39(1):10-39. doi:10.1002/phar.2209
- World Health Organization (WHO). Critically Important Antimicrobials for Human Medicine, 6th Revision. WHO; 2019. Available at: who.int
- Karaiskos I, Souli M, Galani I, Giamarellou H. Colistin: still a lifesaver for the 21st century? Expert Opinion on Drug Metabolism & Toxicology. 2017;13(1):59-71. doi:10.1080/17425255.2017.1230200
- Infectious Diseases Society of America (IDSA). Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. 2023 Update. Available at: idsociety.org
- European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 14.0, 2024. Available at: eucast.org
- Vardakas KZ, Falagas ME. Colistin versus polymyxin B for the treatment of patients with multidrug-resistant Gram-negative infections: a systematic review and meta-analysis. International Journal of Antimicrobial Agents. 2017;49(2):233-238.
- British National Formulary (BNF). Colistimethate sodium. NICE. Available at: bnf.nice.org.uk
- Dalfino L, Puntillo F, Mosca A, et al. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? Clinical Infectious Diseases. 2012;54(12):1720-1726. doi:10.1093/cid/cis286
Editorial Team
Written by the iMedic Medical Editorial Team — specialists in infectious disease and clinical pharmacology with extensive experience in antimicrobial therapy and critical care medicine.
Reviewed by the iMedic Medical Review Board — an independent panel of physicians and pharmacists who verify all content against international guidelines (WHO, EMA, IDSA, EUCAST).
Evidence standard: All medical claims in this article are supported by Level 1A evidence (systematic reviews and meta-analyses of randomised controlled trials) or authoritative international guidelines. The GRADE framework is used to assess the quality of evidence.
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