colistin
Regulatory sources consulted
Approved indications
- Serious systemic infections caused by susceptible aerobic gram-negative organisms when options are limited.
Contraindications
Absolute
- Hypersensitivity to colistimethate sodium or any of its components.
Clinical warnings
- It may cause nephrotoxicity, neurotoxicity, apnea, and neuromuscular blockade; monitor renal function, electrolytes, paresthesias, weakness, and respiration. — CIMA/AEMPS, ficha técnica 74156
- In myasthenia gravis, use colistimethate sodium with extreme caution and only when clearly necessary because of the risk of neuromuscular blockade and apnea. — CIMA/AEMPS, ficha técnica 74156
- Major warning · Pseudo-Bartter syndrome and electrolyte disturbances have been reported; monitor potassium, magnesium, and calcium. Use cautiously in porphyria. — CIMA/AEMPS, ficha técnica 74156
Drug interactions
- HighNephrotoxic or neurotoxic drugs
Mechanism: Renal and neurologic toxicity may be additive.
Recommendation: Avoid if possible; if combined, intensify monitoring.
CIMA/AEMPS, ficha técnica 74156
- HighNondepolarizing neuromuscular blockers
Mechanism: They may potentiate blockade and cause apnea.
Recommendation: Avoid or monitor respiration and prepare ventilatory support.
CIMA/AEMPS, ficha técnica 74156
Adverse events
Common (≥1%)
Renal impairment, paresthesias, dizziness, and electrolyte disturbances
Rare but serious
Renal failure, apnea, neuromuscular blockade, and severe neurotoxicity
Pregnancy and lactation
Use during pregnancy only if benefit outweighs risk. Avoid breastfeeding during treatment.
Recent literature (PubMed)
There is a need for additional therapeutic options for serious infections caused by Gram-negative pathogens. In the phase 3, descriptive REVISIT study, we investigated the safety and efficacy of aztreonam-avibactam in the treatment of complicated intra-abdominal infections or hospital-acquired pneumonia or ventilator-associated pneumonia (HAP-VAP) caused, or suspected to be caused, by Gram-negative bacteria. This prospective, multinational, open-label, central assessor-masked study enrolled adults who were hospitalised with a complicated intra-abdominal infection or HAP-VAP. Patients were randomly allocated via block randomisation using interactive response technology stratified by infection type in a 2:1 ratio to aztreonam-avibactam (with metronidazole for complicated intra-abdominal infection) or meropenem with or without colistin for 5-14 days for complicated intra-abdominal infection or 7-14 days for HAP-VAP. The primary endpoint was clinical cure at the test-of-cure visit (within 3 days before or after day 28) in the intention-to-treat (ITT) population. Secondary endpoints included 28-day mortality in the ITT population and safety in patients in the ITT population who received study drug (safety analysis set). No formal hypothesis testing was planned. The study was registered with ClinicalTrials.gov (NCT03329092) and EudraCT (2017-002742-68) and is complete. Between April 5, 2018, and Feb 23, 2023, we screened 461 patients. 422 patients were enrolled and randomly allocated (282 in the aztreonam-avibactam group and 140 in the meropenem group, forming the ITT analysis set), of whom ten patients (seven in the aztreonam-avibactam group and three in the meropenem group) were randomly allocated but did not receive study treatment. 271 (64%) of 422 patients had at least one Gram-negative pathogen from an adequate specimen identified at baseline. The most frequent baseline pathogens were Enterobacterales (252 [93%] of 271). Overall, 19 (24%) of 80 isolates tested for c
An urgent need exists for antibiotics to treat infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC). Sulbactam-durlobactam is a β-lactam-β-lactamase inhibitor combination with activity against Acinetobacter, including multidrug-resistant strains. In a phase 3, pathogen-specific, randomised controlled trial, we compared the efficacy and safety of sulbactam-durlobactam versus colistin, both in combination with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC. The ATTACK trial was done at 59 clinical sites in 16 countries. Adults aged 18 years or older with ABC-confirmed hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bloodstream infections were randomised 1:1 using a block size of four to sulbactam-durlobactam (1·0 g of each drug in combination over 3 h every 6 h) or colistin (2·5 mg/kg over 30 min every 12 h) for 7-14 days. All patients received imipenem-cilastatin (1·0 g of each drug in combination over 1 h every 6 h) as background therapy. The primary efficacy endpoint was 28-day all-cause mortality in patients with laboratory-confirmed carbapenem-resistant ABC (the carbapenem-resistant ABC microbiologically modified intention-to-treat population). Non-inferiority was concluded if the upper bound of the 95% CI for the treatment difference was less than +20%. The primary safety endpoint was incidence of nephrotoxicity assessed using modified Risk, Injury, Failure, Loss, End-stage renal disease criteria measured by creatinine level or glomerular filtration rate through day 42. This trial is registered at ClinicalTrials.gov, NCT03894046. Between Sep 5, 2019, and July 26, 2021, 181 patients were randomly assigned to sulbactam-durlobactam or colistin (176 hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, or ventilated pneumonia; and five bloodstream infections); 125 patients w
The increase in nosocomial infections by beta-lactamase producing Gram-negative bacilli constitutes a therapeutic challenge. The combination of ceftazidime-avibactam offers a very interesting therapeutic option for nosocomial pneumonia caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, multidrug-resistant Pseudomonas aeruginosa, and other enterobacteria. Compared to carbapenems, ceftazidime-avibactam has demonstrated non-inferiority in the treatment of nosocomial pneumonia including better clinical and microbiological cure rates and mortality compared to colistin. The limitation of ceftazidime-avibactam in the treatment of infections caused by metallo-beta-lactamase-producing Enterobacteriaceae can be overcome with the addition of aztreonam.
Non-cystic fibrosis (CF) bronchiectasis is a chronic lung condition caused by permanent bronchial dilatation and inflammation and is characterized by daily cough, sputum, and recurrent exacerbations. Approximately 500 000 people in the US have non-CF bronchiectasis. Non-CF bronchiectasis may be associated with prior pneumonia, infection with nontuberculous mycobacteria or tuberculosis, genetic conditions (eg, α1-antitrypsin deficiency, primary ciliary dyskinesia), autoimmune diseases (eg, rheumatoid arthritis, inflammatory bowel disease), allergic bronchopulmonary aspergillosis, and immunodeficiency syndromes (eg, common variable immunodeficiency). Up to 38% of cases are idiopathic. According to US data, conditions associated with non-CF bronchiectasis include gastroesophageal reflux disease (47%), asthma (29%), and chronic obstructive pulmonary disease (20%). The prevalence of non-CF bronchiectasis increases substantially with age (7 per 100 000 in individuals 18-34 years vs 812 per 100 000 in those ≥75 years) and is more common in women than men (180 vs 95 per 100 000). Diagnosis is confirmed with noncontrast chest computed tomography showing dilated airways and often airway thickening and mucus plugging. Initial diagnostic evaluation involves blood testing (complete blood cell count with differential); immunoglobulin quantification testing (IgG, IgA, IgE, and IgM); sputum cultures for bacteria, mycobacteria, and fungi; and prebronchodilator and postbronchodilator spirometry. Treatment includes airway clearance techniques; nebulization of saline to loosen tenacious secretions; and regular exercise, participation in pulmonary rehabilitation, or both. Inhaled bronchodilators (β-agonists and antimuscarinic agents) and inhaled corticosteroids are indicated for patients with bronchiectasis who have asthma or chronic obstructive pulmonary disease. Exacerbations of bronchiectasis, which typically present with increased cough and sputum and worsened fatigue, are associate
Patients with severe carbapenem-resistant Acinetobacter baumannii (CRAB) infections currently face significant treatment challenges. When patients display signs of infection and the clinical suspicion of CRAB infections is high, appropriate treatment should be immediately provided. However, current treatment plans and clinical data for CRAB are limited. Inherent and acquired resistance mechanisms, as well as host factors, significantly restrict options for empirical medication. Moreover, inappropriate drug coverage can have detrimental effects on patients. Most existing studies have limitations, such as a restricted sample size, and are predominantly observational or non-randomized, which report significant variability in patient infection severity and comorbidities. Therefore, a gold-standard therapy remains lacking. Current and future treatment options of infections due to CRAB were described in this review. The dose and considerable side effects restrict treatment options for polymyxins, and high doses of ampicillin-sulbactam or tigecycline appear to be the best option at the time of initial treatment. Moreover, new drugs such as durlobactam and cefiderocol have substantial therapeutic capabilities and may be effective salvage treatments. Bacteriophages and antimicrobial peptides may serve as alternative treatment options in the near future. The advantages of a combination antimicrobial regimen appear to predominate those of a single regimen. Despite its significant nephrotoxicity, colistin is considered a primary treatment and is often used in combination with antimicrobials, such as tigecycline, ampicillin-sulbactam, meropenem, or fosfomycin. The Infectious Diseases Society of America (IDSA) has deemed high-dose ampicillin-sulbactam, which is typically combined with high-dose tigecycline, polymyxin, and other antibacterial agents, the best option for treating serious CRAB infections. A rational combination of drug use and the exploration of new therapeutic drug