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Understanding Colistin: Mechanism of Action, Clinical Uses, and Dosage Guidelines

Writer: MaytaMayta
Jun 14, 20243 min read

Introduction

Colistin, also known as polymyxin E, is a critical antibiotic in modern medicine, particularly in the fight against multi-drug resistant Gram-negative bacterial infections. This post will explore the mechanism of action of colistin, its clinical uses, associated risks, and detailed dosage guidelines to ensure optimal use in various clinical scenarios.

Mechanism of Action

Interaction with Bacterial Cell Membranes

Colistin is a cationic polypeptide antibiotic that targets the outer membrane of Gram-negative bacteria. It interacts electrostatically with the anionic lipopolysaccharides (LPS) and phospholipids, displacing stabilizing divalent cations like calcium and magnesium.

Disruption of Cell Membrane Integrity

After initial binding, colistin inserts itself into the outer and inner bacterial membranes, causing disruption of membrane structure and increased permeability. This leads to leakage of intracellular contents and bacterial cell death.

Bactericidal Effect

The compromised membrane integrity results in cell lysis. Additionally, colistin induces the production of reactive oxygen species (ROS), further damaging bacterial cells and enhancing its bactericidal action.

Clinical Use of Colistin

Colistin is primarily reserved for treating severe infections caused by multi-drug resistant Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Its use is typically restricted to situations where alternative treatments are ineffective or unavailable.

Nephrotoxicity: A Major Concern

While colistin is effective against resistant bacteria, its use is not without risks. One of the significant adverse effects of colistin is nephrotoxicity, which can lead to acute kidney injury (AKI).

Nephrotoxic Mechanism

Colistin can cause damage to renal tubular cells, resulting in impaired kidney function. This damage is often dose-dependent, necessitating careful monitoring and dose adjustments based on renal function.

Clinical Management

Patients on colistin therapy require regular monitoring of renal function. Dosage adjustments may be needed to minimize the risk of nephrotoxicity while ensuring the antibiotic remains effective.

Colistin Dosage Guide

Adult Dosage

For Severe Infections (Including Multi-Drug Resistant Gram-Negative Infections):

  • Loading Dose: 9 million international units (MIU) intravenously (IV) as a single dose.

  • Maintenance Dose: 4.5 million international units (MIU) IV every 12 hours.

For Patients with Renal Impairment:

  • Creatinine Clearance (CrCl) 50-79 ml/min: 2.5-3.8 mg/kg/day divided every 12 hours.

  • Creatinine Clearance (CrCl) 30-49 ml/min: 2.5 mg/kg/day divided every 12-24 hours.

  • Creatinine Clearance (CrCl) 10-29 ml/min: 1.5 mg/kg/day every 36 hours.

Pediatric Dosage

General Infections:

  • Loading Dose: 75,000-150,000 IU/kg IV as a single dose.

  • Maintenance Dose: 75,000 IU/kg/day divided every 8-12 hours.

For Cystic Fibrosis:

  • Inhalation: 75 mg in normal saline (NSS) 4 ml via nebulizer twice daily.

For Severe Infections:

  • Maintenance Dose: 1-4 million units IV every 8 hours.

Specific Dosage Adjustments

For Inhalation Therapy:

  • Inhalation: 75 mg in 4 ml normal saline via nebulizer twice daily.

Formulation Availability

  • Injection: 150 mg colistin (360 mg colistimethate sodium).

Example Prescription Patterns

For an Adult with Normal Renal Function:

  • Loading Dose: Colistin (9 MIU) IV as a single dose.

  • Maintenance Dose: Colistin (4.5 MIU) IV every 12 hours.

For a Pediatric Patient with Severe Infection:

  • Loading Dose: Colistin (75,000 IU/kg) IV as a single dose.

  • Maintenance Dose: Colistin (75,000 IU/kg/day) divided every 8-12 hours.

For an Adult with Renal Impairment (CrCl 30-49 ml/min):

  • Maintenance Dose: Colistin (2.5 mg/kg/day) divided every 12-24 hours.

Important Considerations

  • Adjust dosages based on renal function to prevent toxicity.

  • Monitor renal function regularly during treatment.

  • Administer with caution in patients with existing renal impairment.

Conclusion

Colistin remains a crucial antibiotic in the fight against multi-drug resistant Gram-negative infections. Understanding its mechanism of action, clinical uses, potential nephrotoxicity, and appropriate dosing is essential for optimizing its clinical efficacy and safety. By balancing the benefits of colistin against its potential harms, healthcare providers can make informed decisions to improve patient outcomes in challenging infections.

 
 
 

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Message for International Readers
Understanding My Medical Context in Thailand

By Uniqcret, M.D.
 

Dear readers,
 

My name is Uniqcret, which is my pen name used in all my medical writings. I am a Doctor of Medicine trained and currently practicing in Thailand, a developing country in Southeast Asia.
 

The medical training environment in Thailand is vastly different from that of Western countries. Our education system heavily emphasizes rote memorization—those who excel are often seen as "walking encyclopedias." Unfortunately, those who question, critically analyze, or solve problems efficiently may sometimes be overlooked, despite having exceptional clinical thinking skills.
 

One key difference is in patient access. In Thailand, patients can walk directly into tertiary care centers without going through a referral system or primary care gatekeeping. This creates an intense clinical workload for doctors and trainees alike. From the age of 20, I was already seeing real patients, performing procedures, and assisting in operations—not in simulations, but in live clinical situations. Long work hours, sometimes exceeding 48 hours without sleep, are considered normal for young doctors here.
 

Many of the insights I share are based on first-hand experiences, feedback from attending physicians, and real clinical practice. In our culture, teaching often involves intense feedback—what we call "โดนซอย" (being sliced). While this may seem harsh, it pushes us to grow stronger, think faster, and become more capable under pressure. You could say our motto is “no pain, no gain.”
 

Please be aware that while my articles may contain clinically accurate insights, they are not always suitable as direct references for academic papers, as some content is generated through AI support based on my knowledge and clinical exposure. If you wish to use the content for academic or clinical reference, I strongly recommend cross-verifying it with high-quality sources or databases. You may even copy sections of my articles into AI tools or search engines to find original sources for further reading.
 

I believe that my knowledge—built from real clinical experience in a high-intensity, under-resourced healthcare system—can offer valuable perspectives that are hard to find in textbooks. Whether you're a student, clinician, or educator, I hope my content adds insight and value to your journey.
 

With respect and solidarity,

Uniqcret, M.D.

Physician | Educator | Writer
Thailand

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