Condition
Multidrug-Resistant Bacterial Infections
Multidrug-resistant infections arise when bacteria adapt to withstand several common antibiotics, leaving fewer medicines that work. Colistin and polymyxin B, older last-resort antibiotics, have the strongest evidence: pooled trials found colistin useful against resistant Gram-negative bacteria, and about 70% of people given polymyxin B in one study were alive after 14 days. The colistin trials were few and small, and the polymyxin B work was observational.
Sources: PMID 25199968; PMID 40047414
- Updated
- How we grade
- 82 studies cited
- Supplements studied
- 0
- Medicines and peptides
- 2
- Graded outcomes
- 10
Prescription medicines and peptides studied, for context
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| MDR Gram-Negative Infections Meta-analysis of 5 RCTs (n=377): Effective last-resort option for MDR infections. Cochrane reviews support use for pneumonia, BSI. Clinical success 59.5% in PK study. WHO Essential Medicine designation. | Improves (the measure goes up) | Moderate effect | 16 studies | |||
Studies that measured mdr gram-negative infections | ||||||
| Ventilator-Associated Pneumonia Most common indication in RCTs. Nebulized colistin shows similar efficacy to IV with potentially less nephrotoxicity. Clinical cure rates comparable to β-lactam regimens. | Improves (the measure goes up) | Moderate effect | 15 studies | |||
Studies that measured ventilator-associated pneumonia | ||||||
| Nephrotoxicity Incidence SAFETY CONCERN: Meta-analysis: 36.2% nephrotoxicity vs 15% comparators (RR 2.40, NNH=5). Comprehensive study (n=178): 44.9% incidence. Median onset 4-6 days. 75% recovery within 10 days of discontinuation. Reversible tubular damage. | Worsens (the measure goes up) | Large effect | 14 studies | |||
Studies that measured nephrotoxicity incidence | ||||||
| Pediatric/Neonatal Infections Systematic review (17 studies, n=312 neonates/infants): Effective for BSI, pneumonia, meningitis. Doses 25,000-225,000 IU/kg/day. PK studies suggest >150,000 IU/kg/day needed. Limited nephrotoxicity data in children. | Improves (the measure goes up) | Moderate effect | 15 studies | |||
Studies that measured pediatric/neonatal infections | ||||||
| Neurotoxicity Risk SAFETY CONCERN: Neurotoxicity reported including paresthesias, ataxia, neuromuscular blockade. Appears reversible upon discontinuation or dose reduction. Less common than nephrotoxicity. | Worsens (the measure goes up) | Small effect | 15 studies | |||
Studies that measured neurotoxicity risk | ||||||
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Carbapenem-Resistant GNB Infections Prospective multicenter study (n=312): 14-day survival 70.5% for CRGNB infections. Site-specific outcomes: LRTI 67.7%, IAI 80.3%, BSI 69.7% survival. Last-resort efficacy against otherwise untreatable MDR pathogens. | Improves (the measure goes up) | Moderate effect | 12 studies | |||
Studies that measured carbapenem-resistant gnb infections
| ||||||
| Nephrotoxicity Risk SAFETY CONCERN: AKI incidence 35-60% across studies. Risk factors: duration of use, BMI, advanced age, concomitant nephrotoxins. Generally reversible upon discontinuation. Possibly milder than colistin-associated nephrotoxicity. | Worsens (the measure goes up) | Moderate effect | 9 studies | |||
Studies that measured nephrotoxicity risk | ||||||
| MDR Pseudomonas aeruginosa Rapid bactericidal activity against MDR P. aeruginosa with low acquired resistance rates. MIC90 generally 1-2 mg/L. Essential option when all other antipseudomonal agents have failed. | Improves (the measure goes up) | Moderate effect | 7 studies | |||
Studies that measured mdr pseudomonas aeruginosa | ||||||
| MDR Acinetobacter baumannii Retained activity against extensively drug-resistant A. baumannii. Organism cleared in 88% of patients in clinical studies. Critical therapy for nosocomial Acinetobacter infections. | Improves (the measure goes up) | Moderate effect | 7 studies | |||
Studies that measured mdr acinetobacter baumannii | ||||||
| Pediatric Efficacy Population PK study (n=19 pediatric patients): Clinical success 73.7% with only 5.3% AKI rate. Weight-based dosing (1.33-2.53 mg/kg/day). Lower nephrotoxicity risk in pediatric population. | Improves (the measure goes up) | Moderate effect | 7 studies | |||
Studies that measured pediatric efficacy | ||||||
Key findings
- MDR Gram-Negative InfectionsImproves (the measure goes up)
- Ventilator-Associated PneumoniaImproves (the measure goes up)
- Nephrotoxicity IncidenceWorsens (the measure goes up)
Safety notes in the studies
- Risk factors: duration of use, BMI, advanced age, concomitant nephrotoxins.
- Lower nephrotoxicity risk in pediatric population.
Studies cited
82 studies from PubMed
- Prevalence of colistin resistance in clinical Klebsiella pneumoniae isolates: a systematic review and meta-analysis.
- Novel strategies for combating colistin-resistant isolates: a review.
- Polymyxin B delivery systems: smart solutions for improved antibacterial activity and reduced toxicity.
- Polymyxin B and silver nanoparticles: a nanotechnology-driven approach to overcome antibiotic resistance.
- Relationship between plasma polymyxin B concentrations and acute kidney injury in critically ill elderly patients: Findings from a prospective study.
- Battle of polymyxin induced nephrotoxicity: Polymyxin B versus colistin.
- Prevention of colistin-induced neurotoxicity: a narrative review of preclinical data.
- Clinical outcomes and pharmacokinetics/pharmacodynamics of intravenous polymyxin B treatment for various site carbapenem-resistant gram-negative bacterial infections: a prospective observational multicenter study
- Unravelling the Hepatic Elimination Mechanisms of Colistin.
- Liposomes Co-Delivering Curcumin and Colistin to Overcome Colistin Resistance in Bacterial Infections.
- Prostaglandin F2α analogue, bimatoprost ameliorates colistin-induced nephrotoxicity.
- Polymyxin B Hemoperfusion in Septic Shock: Finding the Right Patients by Analyzing Real-World Big Data.
- Polymyxin B-related neurotoxicity: a brief case report.
- Population Pharmacokinetics of Colistin Sulfate in Critically Ill Patients: Exposure and Clinical Efficacy
- Efficacy of stem cell-based therapies for colistin-induced nephrotoxicity.
- Global colistin use: a review of the emergence of resistant Enterobacterales and the impact on their genetic basis.
- Prevalence of colistin resistance of Klebsiella pneumoniae isolates in Iran: a systematic review and meta-analysis.
- Molecular mechanisms and clonal lineages of colistin-resistant bacteria across the African continent: a scoping review.
- Effectiveness, nephrotoxicity, and therapeutic drug monitoring of polymyxin B in nosocomial pneumonia among critically ill patients
- Population pharmacokinetics and clinical outcomes of polymyxin B in paediatric patients with multidrug-resistant Gram-negative bacterial infections
- Trough polymyxin B plasma concentration is an independent risk factor for its nephrotoxicity.
- Population pharmacokinetics of polymyxin B and dosage strategy in critically ill patients with/without continuous renal replacement therapy.
- Efficacy and safety of intraventricular polymyxin B plus continuous ventricular drainage for the treatment of intracranial infection caused by drug-resistant Acinetobacter baumannii.
- Prevention of colistin induced nephrotoxicity: a review of preclinical and clinical data.
- Can magnesium sulfate prophylaxis reduce colistin nephrotoxicity?
- Mobilized colistin resistance (mcr) genes from 1 to 10: a comprehensive review.
- Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study
- Polymyxin B-modified conjugated oligomer nanoparticle for targeted identification and enhanced photodynamic antimicrobial therapy.
- Does renal function matter for polymyxin B?
- Risk factors for nephrotoxicity associated with polymyxin B therapy in Chinese patients.
- Effect of Different Dosage Frequency of Polymyxin B on Rat Nephrotoxicity.
- Nanocapsule system tackles polymyxin B toxicity.
- Efficacy and safety of polymyxin B in carbapenem-resistant gram-negative organisms infections.
- Assesment of colistin related side effects in premature neonates.
- Colistin and its role in the Era of antibiotic resistance: an extended review (2000-2019).
- Colistin heteroresistance in Acinetobacter spp.: systematic review and meta-analysis of the prevalence and discussion of the mechanisms and potential therapeutic implications.
- Lysophosphatidylcholine Potentiates Antibacterial Activity of Polymyxin B.
- The Use of Colistin for the Treatment of Multidrug-resistant Gram-negative Infections in Neonates and Infants: A Review of the Literature
- Safety and efficacy of colistin alone or in combination in adults with Acinetobacter baumannii infection: A systematic review and meta-analysis.
- Colistin induced peripheral neurotoxicity involves mitochondrial dysfunction and oxidative stress in mice.
- Antimicrobial Susceptibility Testing for Polymyxins: Challenges, Issues, and Recommendations.
- History, Chemistry and Antibacterial Spectrum.
- Colistin Use in Patients with Extreme Renal Function: From Dialysis to Augmented Clearance.
- Polymyxin B clinical outcomes: A prospective study of patients undergoing intravenous treatment
- Treatment with a polymyxin B filter to capture endotoxin in sepsis patients: is there a signal for therapeutic efficacy?
- Rational use of intravenous polymyxin B and colistin: A review.
- Population Pharmacokinetics of Polymyxin B
- Gelofusine Ameliorates Colistin-Induced Nephrotoxicity.
- A network perspective on antimicrobial peptide combination therapies: the potential of colistin, polymyxin B and nisin.
- Modulation by Polymyxin-B Hemoperfusion of Inflammatory Response Related to Severe Peritonitis.
- Nephrotoxicity of Polymyxins: Is There Any Difference between Colistimethate and Polymyxin B?
- Role of Renal Drug Exposure in Polymyxin B-Induced Nephrotoxicity.
- Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?
- Plasmid-mediated colistin resistance: an additional antibiotic resistance menace.
- Resistance to colistin: what is the fate for this antibiotic in pig production?
- Colistin Use in Patients With Reduced Kidney Function.
- Polymyxin B Nephrotoxicity: From Organ to Cell Damage.
- Colistin: understanding and applying recent pharmacokinetic advances
- A review on colistin nephrotoxicity
- Colistin: efficacy and safety in different populations.
- Colistin neurotoxicity: revisited.
- Colistin: Revival of an Old Polymyxin Antibiotic.
- Colistin: an antibiotic and its role in multiresistant Gram-negative infections.
- Polymyxin B hemoperfusion in sepsis: growing body of evidence and occasional conflicting results.
- Colistin-mediated neurotoxicity.
- Systematic review of the evidence for rational dosing of colistin.
- Colistin for the treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: a systematic review and meta-analysis.
- Uptake of polymyxin B into renal cells.
- Colistin: re-emergence of the 'forgotten' antimicrobial agent.
- Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens
- PmrB mutations promote polymyxin resistance of Pseudomonas aeruginosa isolated from colistin-treated cystic fibrosis patients.
- Colistin: new lessons on an old antibiotic.
- Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies.
- Polymyxin B-immobilized fiber column hemoperfusion therapy for septic shock.
- Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing
- Polymyxin E sulfate-loaded liposome for intravenous use: preparation, lyophilization, and toxicity assessment in vivo.
- Multidrug-resistant Gram-negative infections: the use of colistin
- Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review
- Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections
- Polymyxin B nephrotoxicity and efficacy against nosocomial infections caused by multiresistant gram-negative bacteria
- Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria
- Inhibition of lipopolysaccharide-induced TNF-alpha production by semisynthetic polymyxin-B conjugated dextran.