Note: Reserve for extensively drug-resistant gram-negative infections (eg, carbapenem-resistant Enterobacterales or A. baumannii, difficult to treat P. aeruginosa) when other agents cannot be used (Ref). Dosage expressed in terms of mg of colistin base activity (CBA). CBA 1 mg is defined to be equivalent to colistimethate sodium (CMS) 30,000 units which is equivalent to ~2.4 mg CMS (see table below) (Ref).
Colistimethate Sodium |
Colistimethate Sodium |
Colistin-Base Activity |
12,500 units |
1 mg |
0.4 mg |
150,000 units |
12 mg |
5 mg |
1,000,000 units |
80 mg |
34 mg |
4,500,000 units |
360 mg |
150 mg |
9,000,000 units |
720 mg |
300 mg |
Bloodstream infection:
Note: When polymyxin use is warranted, polymyxin B is preferred over colistimethate due to significant interpatient variability in pharmacokinetics, slower attainment of desired plasma concentrations, and increased risk of nephrotoxicity with colistimethate (Ref). To minimize development of resistance, use in combination with other antibiotics, depending on infection site and susceptibilities (Ref).
IV: 300 mg colistin base activity (CBA) loading dose followed 12 hours later with 150 to 180 mg CBA twice daily (Ref). Usual duration is 7 to 14 days depending on source, extent of infection, and clinical response (Ref).
Bronchiectasis, exacerbation prevention (off-label use):
Note: Reserve for patients with multidrug-resistant gram-negative pathogens in the sputum and either >3 exacerbations per year or severe exacerbations (Ref). Dose not well defined and varies widely across studies.
Inhalation for nebulization (off-label route): 30 to 150 mg colistin base activity (CBA) via nebulizer once or twice daily (maximum dose: 150 mg CBA twice daily) (Ref).
Cystic fibrosis (off-label use):
Acute pulmonary exacerbation: Note: To minimize development of resistance, use in combination with other antibiotics depending on susceptibilities (Ref).
IV: 2.5 to 5 mg/kg/day colistin base activity (CBA) in 3 divided doses. Maximum dose not well defined (Ref); some experts suggest a maximum of 300 mg CBA/day in patients with cystic fibrosis (Ref). Treatment duration is 10 to 14 days depending on patient-specific factors, including initial response to therapy (Ref).
Chronic P. aeruginosa pulmonary infection: Inhalation for nebulization (off-label route): 75 to 150 mg CBA via nebulizer twice daily (Ref). Administer in repeated cycles of 28 days on drug followed by 28 days off drug (Ref).
Intra-abdominal infection:
Note: When polymyxin use is warranted, polymyxin B is preferred over colistimethate due to significant interpatient variability in pharmacokinetics, slower attainment of desired plasma concentrations, and increased risk of nephrotoxicity with colistimethate (Ref). To minimize development of resistance, use in combination with other antibiotics, depending on infection site and susceptibilities (Ref).
IV: 300 mg colistin base activity (CBA) loading dose followed 12 hours later with 150 to 180 mg CBA twice daily (Ref). Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref).
Meningitis, bacterial:
Note: When systemic polymyxin use is warranted, polymyxin B is preferred over colistimethate due to significant interpatient variability in pharmacokinetics, slower attainment of desired plasma concentrations, and increased risk of nephrotoxicity with colistimethate (Ref). To minimize development of resistance, use in combination with other antibiotics, depending on infection site and susceptibilities (Ref). Intraventricular/intrathecal administration is generally reserved for meningitis or ventriculitis that is refractory to appropriate parenteral therapy or associated with intraventricular devices that cannot be removed (Ref).
IV: 300 mg colistin base activity (CBA) loading dose followed 12 hours later with 150 to 180 mg CBA twice daily (Ref). Treatment duration is ≥10 to 14 days (Ref); some experts recommend ≥21 days (Ref).
Intrathecal/intraventricular (adjunctive agent) (off-label route) (use a preservative-free preparation): 4.2 mg CBA per day in 1 or 2 divided doses; administer in combination with appropriate systemic antimicrobial therapy (Ref). Note: When intraventricular colistimethate is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in cerebrospinal fluid) (Ref).
Pneumonia, hospital-acquired or ventilator-associated:
Note: When systemic polymyxin use is warranted, polymyxin B is preferred over colistimethate due to significant interpatient variability in pharmacokinetics, slower attainment of desired plasma concentrations, and increased risk of nephrotoxicity with colistimethate (Ref). To minimize development of resistance, use in combination with other antibiotics, depending on infection site and susceptibilities (Ref). Some experts prefer to add inhaled colistimethate for patients with serious hospital-acquired or ventilator-associated pneumonia that requires treatment with IV colistimethate due to low lung concentrations with IV administration (Ref).
IV: 300 mg colistin base activity (CBA) loading dose followed 12 hours later with 150 to 180 mg CBA twice daily (Ref). Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref).
Inhalation for nebulization (adjunctive agent) (off-label route): Dose not well defined: 75 to 150 mg CBA twice daily in combination with systemic antimicrobial therapy (Ref).
Sepsis and septic shock:
Note: When polymyxin use is warranted, polymyxin B is preferred over colistimethate due to significant interpatient variability in pharmacokinetics, slower attainment of desired plasma concentrations, and increased risk of nephrotoxicity with colistimethate (Ref). To minimize development of resistance, use in combination with other antibiotics, depending on infection site and susceptibilities (Ref).
IV: 300 mg colistin base activity (CBA) loading dose followed 12 hours later with 150 to 180 mg CBA twice daily (Ref); use in combination with other appropriate agents. Initiate therapy as soon as possible and preferably within 1 hour of recognition of sepsis or septic shock. Duration is dependent on underlying source and patient response; short courses are preferred, when appropriate. Discontinue if a noninfectious etiology is identified (Ref).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms):
Note: Colistimethate is the preferred polymyxin for urinary tract infections because of higher urinary concentrations compared to polymyxin B (Ref). To minimize development of resistance, may use in combination with other antibiotics, depending on susceptibilities (Ref).
IV: 300 mg colistin base activity (CBA) loading dose followed 12 hours later with 150 to 180 mg CBA twice daily (Ref). Total duration of therapy ranges from 5 to 14 days; for patients with symptomatic improvement within the first 48 to 72 hours of therapy, some experts recommend shorter courses of 7 to 10 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Dosage expressed in terms of colistin base activity (CBA); although reported conversions have varied slightly in the literature, CBA 1 mg is defined to be equivalent to colistimethate sodium 30,000 units (Ref). These dosing recommendations should achieve a target average colistin steady-state plasma concentration of 2 mg/L and are derived from analysis of pharmacokinetic data in critically ill patients (Ref). For inhaled, intrathecal, and intraventricular colistin, there are no specific dosage adjustments recommended (has not been studied); however, need for adjustment unlikely due to low systemic absorption (Ref).
Altered kidney function:
Loading dose: IV: 300 mg CBA, followed by a maintenance dose based on CrCl (Ref) calculated using the Cockcroft-Gault equation with an adjusted body weight (ideal body weight [IBW] + 0.4 [total body weight – IBW]) (Ref).
Maintenance dose: IV: The following total daily maintenance doses (administered in 2 divided doses) are recommended (Ref); begin maintenance dose 12 hours after the loading dose:
CrCl ≥90 mL/minute: 360 mg CBA/day.
CrCl 80 to <90 mL/minute: 340 mg CBA/day.
CrCl 70 to <80 mL/minute: 300 mg CBA/day.
CrCl 60 to <70 mL/minute: 275 mg CBA/day.
CrCl 50 to <60 mL/minute: 245 mg CBA/day.
CrCl 40 to <50 mL/minute: 220 mg CBA/day.
CrCl 30 to <40 mL/minute: 195 mg CBA/day.
CrCl 20 to <30 mL/minute: 175 mg CBA/day.
CrCl 10 to <20 mL/minute: 160 mg CBA/day.
CrCl 5 to <10 mL/minute: 145 mg CBA/day.
CrCl <5 mL/minute: 130 mg CBA/day.
Alternative renal dosing strategy (Ref):
IV:
For critically ill patients, a loading dose of 300 mg CBA should be administered followed by a maintenance dose based on CrCl. The following total daily maintenance doses (administered in 2 or 3 divided doses) are recommended; begin maintenance dose 12 hours after the loading dose:
CrCl ≥50 mL/minute: 300 mg CBA/day; patients with good kidney function (CrCl ≥80 mL/minute) may require higher doses >300 mg/day.
CrCl 30 to <50 mL/minute: 183 to 250 mg CBA/day.
CrCl 10 to <30 mL/minute: 150 to 183 mg CBA/day.
CrCl <10 mL/minute: 117 mg CBA/day.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: 360 mg CBA/day (Ref).
Note: No definitive studies have evaluated colistin pharmacokinetics in ARC. Patients with ARC receiving conventional doses required longer treatments than those without ARC (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (~30%) (Ref):
Loading dose: IV: 300 mg CBA (Ref).
Maintenance dose: IV:
Dialysis days: 180 mg CBA on dialysis days (administer after dialysis) (Ref).
Nondialysis days: 130 mg CBA on nondialysis days (Ref).
Peritoneal dialysis: IV: Loading dose: 300 mg CBA followed by 150 to 200 mg CBA once daily as maintenance starting 24 hours after the loading dose (Ref).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour), and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.
IV: Loading dose: 300 mg CBA followed by 220 mg CBA every 12 hours as maintenance starting 12 hours after the loading dose (Ref). Note: The pro-drug CMS is removed by CRRT (~10% per hour), therefore patients receiving CRRT require higher daily doses than patients with normal kidney function (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.
IV: Loading dose: 300 mg CBA followed by maintenance dose based on kidney function and duration of PIRRT session. Add 10% per 1 hour of PIRRT replacement to the recommended baseline daily dose for kidney function (eg, CrCl <5 mL/minute, 130 mg CBA/day); administer in 2 divided doses 12 hours apart starting 12 hours after the loading dose (Ref).
For example, in a patient with a CrCl of <5 mL/minute receiving 10 hours nocturnal PIRRT session each day, the suggested CBA maintenance dose is: 130 mg + (10 hours × 13) = 260 mg CBA/day, administered as 130 mg every 12 hours. PIRRT session should begin 1 to 2 hours after the afternoon/evening dose (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling.
CNS toxicity: Dose reduction may reduce neurologic symptoms.
Nephrotoxicity: Withhold treatment if signs of renal impairment occur during treatment.
Refer to adult dosing.
(For additional information see "Colistin (colistimethate): Pediatric drug information")
Note: Due to risk of toxicity and efficacy limitations, systemic use is limited to when less toxic alternatives are not effective or not tolerated. When used, typically recommended as part of combination therapy (Ref). Doses should be based on ideal body weight in obese patients; dosage primarily expressed in terms of colistin base activity (CBA). CBA 1 mg is defined to be equivalent to colistimethate sodium (CMS) 30,000 units, which is equivalent to ~2.4 mg CMS (Ref).
General dosing: Infants, Children, and Adolescents: IM, IV: 2.5 to 5 mg CBA/kg/day divided every 6 to 12 hours (Ref). Higher doses may be necessary in some instances; see dosing for specific indications.
CNS infection (VP-shunt infection, ventriculitis, meningitis), multidrug resistant: Variable doses reported; optimal dose not defined.
Infants and Children: Very limited data available: Intraventricular/Intrathecal: Reported range: 1 to 4.2 mg CBA/dose once daily in combination with systemic antibiotics (Ref). Doses should be individualized based on culture/susceptibility, minimum inhibitory concentration (MIC), and tolerability, with consideration of patient size and cerebrospinal fluid volume. Case reports in patients 2 months to 4 years of age have described a titration regimen in which 1 mg CBA is administered on day 1, followed by 2 mg CBA once daily for 1 to 2 days, then 4 mg CBA once daily thereafter for a total of 8 to 18 days of therapy (Ref). In other case reports, patients aged 1 month to 5 years received intrathecal or intraventricular colistin without titration at a dose of 4.2 mg CBA once daily for 5 to 9 days (Ref). Doses as high as 10 mg CBA (after titration) have been reported to treat multidrug-resistant Acinetobacter baumannii in an infant (Ref).
Adolescents: Very limited data available: Intraventricular/Intrathecal: 4.2 mg CBA/day (equivalent to 10 mg CMS/day) (Ref). Reported range: 2 to 8.3 mg CBA/day in 1 or 2 divided doses; duration of 10 to 14 days most commonly reported; however, use for up to 24 days has been described; most commonly administered in a single daily dose (Ref). In some reports, the dose was titrated up from 2.1 mg CBA once daily to 4.2 mg CBA once daily (Ref).
Cystic fibrosis, pulmonary infection: Limited data available:
IV: Acute pulmonary exacerbation: Children ≥5 years and Adolescents: IV: Usual reported range: 3 to 5 mg CBA/kg/day divided every 8 hours; maximum dose: 100 mg CBA/dose (Ref); doses >5 mg CBA/kg/day (up to 8 mg CBA/kg/day) have been described; however, higher doses are associated with more severe toxicity (Ref). Treatment duration varies and is dependent on patient-specific factors, including response to therapy; typical duration is 10 to 21 days (Ref).
Inhaled: Children and Adolescents: Inhalation: Usual dose: 75 to 150 mg CBA via nebulizer every 12 hours; reported range: 33 to 150 mg CBA/dose; administration of doses ≤66 mg has been reported as frequently as every 8 hours. Duration depends on specific use (eg, maintenance therapy vs eradication therapy) and should be individualized (Ref).
Pulmonary infection due to multidrug-resistant gram-negative bacilli (eg, P. aeruginosa, Acinetobacter spp): Limited data available: Note: Use in combination with systemic therapy (Ref).
Infants: Inhalation: 4 mg/kg/dose via nebulizer every 12 hours; maximum dose: 75 mg/dose (Ref).
Children and Adolescents: Inhalation: 75 to 150 mg CBA via nebulizer every 12 hours (Ref); reported range: 30 to 150 mg CBA/dose every 12 hours (Ref).
Systemic infections (eg, bacteremia, pneumonia) due to multidrug- resistant gram-negative bacilli (alternative agent):
Note: Typically recommended as part of an appropriate combination regimen. Polymyxin B may be preferred over colistin, except for treatment of cystitis (Ref).
Infants, Children, and Adolescents: IM, IV: Loading dose of 2.5 to 5 mg CBA/kg once (maximum dose: 300 mg CBA/dose), followed by 5 mg CBA/kg/day divided every 8 to every 12 hours (maximum dose: 180 mg/dose) (Ref). Population pharmacokinetic studies have suggested that higher doses may be necessary to treat severe/critical illness; doses of ~10 mg CBA/kg/day in divided doses have been described; monitor closely for toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Infants, Children, and Adolescents: Based on experience with other aminoglycosides, the following should be considered:
CNS toxicity: Dose reduction may reduce neurologic symptoms.
Nephrotoxicity: Withhold treatment if signs of renal impairment occur during treatment.
There are no pediatric specific recommendations in the manufacturer’s labeling; in adult patients, dosage adjustment is suggested.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Genitourinary: Nephrotoxicity (18% to 26% [Dalfino 2012; Oliveira 2009])
Renal: Acute renal failure (33% to 60% [Akajagbor 2013; Deryke 2010])
1% to 10%:
Central nervous system: Neurotoxicity (7%; higher incidence with high-dose IV use in cystic fibrosis [Bosso 1991; Koch-Weser 1970])
Frequency not defined:
Central nervous system: Dizziness, oral paresthesia, paresthesia, peripheral paresthesia, seizures, slurred speech, vertigo
Dermatologic: Pruritus, skin rash, urticaria
Gastrointestinal: Clostridioides difficile-associated diarrhea, gastric distress
Genitourinary: Decreased urine output
Hypersensitivity: Anaphylaxis
Renal: Decreased creatinine clearance, increased blood urea nitrogen, increased serum creatinine
Respiratory: Apnea, respiratory distress
Miscellaneous: Fever
Hypersensitivity to colistimethate, colistin, or any component of the formulation.
Concerns related to adverse effects:
• Bronchoconstriction: Use of inhaled colistimethate (off-label route) may result in bronchoconstriction. Use with caution in patients with hyperactive airways; consider administration of a bronchodilator (eg, albuterol) within 15 minutes prior to administration (Le 2010).
• CNS toxicity: Transient, reversible neurological disturbances (eg, dizziness, numbness, paresthesia, generalized pruritus, slurred speech, tingling, vertigo) may occur. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Dose reduction may reduce neurologic symptoms.
• Renal toxicity: Dose-dependent nephrotoxicity has been reported, generally reversible upon discontinuation of treatment.
• Respiratory arrest: Respiratory arrest has been reported with use; impaired renal function may increase the risk for neuromuscular blockade and apnea.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with preexisting renal impairment; dosage adjustments are recommended. Impaired renal function may increase the risk for respiratory arrest.
Other warnings/precautions:
• Appropriate use: Inhalation (off-label route): Once mixed, colistimethate begins conversion to bioactive colistin, a component of which may result in severe pulmonary toxicity (Le 2010). Solutions for inhalation must be mixed immediately prior to administration and used within 24 hours to reduce the incidence of pulmonary toxicity.
• Safety: Potential for dosing errors due to lack of standardization in literature when referring to product and dose. Colistimethate (inactive prodrug) and colistin base strengths are not interchangeable; verify prescribed dose is expressed in terms of colistin base activity prior to dispensing.
Electrolyte disturbances, including hypomagnesemia, hypokalemia, hypocalcemia, and hyponatremia, have been described in neonates receiving IV colistimethate and may require supplementation. Disturbances have been reported mostly in populations mainly comprised of preterm patients, and risk may be higher in the very low-birth-weight population (weighing <1,500 g at birth); monitor electrolytes closely during therapy (Aksoy 2020; Alan 2014; Ambreen 2020; Antachopoulos 2017; Ilhan 2018; İpek 2017). Electrolyte disturbances may be mediated by renal tubulopathy and associated with other manifestations of kidney toxicity (Thomas 2019; Yurttutan 2021).
Neurotoxicity, which may occur in all ages, may present differently in the neonatal population compared to older pediatric patients; in term or preterm neonates, neurotoxicity may present as apnea or seizures; monitor closely (Alan 2014; Ambreen 2020; Çağan 2017; Nakwan 2019).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection [preservative free]:
Coly-Mycin M: 150 mg (1 ea)
Generic: 150 mg (1 ea)
Yes
Solution (reconstituted) (Colistimethate Sodium (CBA) Injection)
150 mg (per each): $12.42 - $35.00
Solution (reconstituted) (Coly-Mycin M Injection)
150 mg (per each): $33.60
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Coly-Mycin M: 150 mg (1 ea)
Generic: 150 mg (1 ea)
IV: Infuse over 30 minutes to 1 hour (Ref).
Inhalation (off-label route): Administer solution via nebulizer (vibrating plate nebulizer may be preferred (Ref)) promptly following preparation to decrease possibility of high concentrations of colistin from forming which may lead to potentially life-threatening lung toxicity. Consider use of a bronchodilator (eg, albuterol) within 15 minutes prior to administration (Ref). If patient is on a ventilator, place medicine in a T-piece at the midinspiratory circuit of the ventilator. One study in adult patients with VAP administered colistimethate over 60 minutes using a vibrating plate nebulizer positioned on the inspiratory limb 10 cm proximal to the Y-piece (Ref).
Note: A case report of fatal lung toxicity implicated in vitro colistin formation from an inhalation solution as a potential etiology, but data regarding the concentration, formulation and storage of the inhaled colistin administered to the patient were not reported (Ref). An acceptable limit of in vitro colistin formation to prevent potential toxicity is unknown. Limited stability data are available regarding the storage of colistin solution for inhaled administration (Ref). Storing for >24 hours may increase the risk for potential lung toxicity; preparation immediately prior to administration is recommended (Ref).
Intrathecal/intraventricular (off-label route): Administer only preservative-free solutions via intrathecal/intraventricular routes. Administer promptly after preparation. Discard unused portion of vial. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow colistimethate solution to equilibrate in the CSF (Ref).
Parenteral:
IM: Administer deep into a large muscle mass (eg, gluteal muscle or lateral part of the thigh).
IV push: Administer over 3 to 5 minutes.
Intermittent IV infusion: Administer over 20 to 60 minutes; most commonly infused over 30 minutes in neonates (Ref).
Inhalation: Administer solution via nebulizer promptly following preparation of solution to decrease possibility of high concentrations of colistin from forming, which may lead to potentially life-threatening lung toxicity. Consider use of a bronchodilator (eg, albuterol) within 15 minutes prior to administration (Ref).
Note: A case report of fatal lung toxicity implicated in vitro colistin formation from an inhalation solution as a potential etiology, but data regarding the concentration, formulation, and storage of the inhaled colistin administered to the patient were not reported (Ref). An acceptable limit of in vitro colistin formation to prevent potential toxicity is unknown. Limited stability data are available regarding the storage of colistin solution for inhaled administration (Ref). Storing for >24 hours may increase the risk for potential lung toxicity; preparation immediately prior to administration is recommended (Ref).
Intraventricular/Intrathecal: Administer only preservative-free solutions via intrathecal/intraventricular routes. Administer promptly after preparation. Discard unused portion of vial. When administering via a ventricular drain, clamp the drain for 15 to 60 minutes to allow equilibration of colistin with cerebrospinal fluid prior to opening the drain (Ref).
Treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, including Pseudomonas aeruginosa, Enterobacter aerogenes, Escherichia coli, and Klebsiella pneumoniae, that are resistant to other antibiotics or in patients who are unable to take other antibiotics.
Bronchiectasis, exacerbation prevention; Cystic fibrosis; Meningitis, bacterial; Pneumonia, hospital-acquired or ventilator-associated
The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Due to the potential for dosing errors, it is recommended that prescriptions for colistimethate be expressed as mg of colistin base activity only.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: May enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Management: Avoid coadministration of colistimethate and aminoglycosides whenever possible due to the risk of nephrotoxicity and neuromuscular blockade. If coadministration cannot be avoided, monitor renal and neuromuscular function. Risk D: Consider therapy modification
Amphotericin B: May enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and amphotericin B whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
Bacitracin (Systemic): Colistimethate may enhance the nephrotoxic effect of Bacitracin (Systemic). Risk X: Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Colistimethate. Risk C: Monitor therapy
Cefaloridine [Cephaloridine]: Colistimethate may enhance the nephrotoxic effect of Cefaloridine [Cephaloridine]. Risk C: Monitor therapy
Cefazedone: May enhance the nephrotoxic effect of Colistimethate. Risk C: Monitor therapy
Cephalothin: May enhance the nephrotoxic effect of Colistimethate. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mecamylamine: Colistimethate may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methoxyflurane: Colistimethate may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination
Netilmicin (Ophthalmic): Colistimethate may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination
Neuromuscular-Blocking Agents: Colistimethate may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Management: If possible, avoid concomitant use of these products. Monitor for deeper, prolonged neuromuscular-blocking effects (respiratory paralysis) in patients receiving concomitant neuromuscular-blocking agents and colistimethate. Risk D: Consider therapy modification
Polymyxin B: Colistimethate may enhance the nephrotoxic effect of Polymyxin B. Polymyxin B may enhance the neuromuscular-blocking effect of Colistimethate. Colistimethate may enhance the neurotoxic effect of Polymyxin B. Management: Coadministration of polymyxin B and other potentially neurotoxic or nephrotoxic agents, such as colistimethate, is generally not recommended. If this combination must be used, monitor carefully for enhanced neurotoxic and nephrotoxic effects. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Colistimethate. Management: Avoid coadministration of colistimethate and vancomycin whenever possible due to the potential for additive or synergistic nephrotoxicity. If coadministration cannot be avoided, closely monitor renal function. Risk D: Consider therapy modification
Adverse events have been observed in animal reproduction studies. Colistimethate crosses the placenta in humans.
Colistin (the active form of colistimethate sodium) and colistin sulphate (another form of colistin) are excreted in human milk. The manufacturer recommends caution if giving colistimethate sodium to a breast-feeding woman. Nondose-related effects could include modification of bowel flora.
Serum creatinine, BUN; urine output; signs of neurotoxicity; signs of bronchospasm (inhalation [off-label route]); colistin serum concentrations (to ensure adequate drug exposure particularly early in therapy) (ESCMID/EUCAST [Tsuji 2019]).
Target serum concentration is 2 mg/L for susceptible organisms (irrespective of reported MIC) (ESCMID/EUCAST [Tsuji 2019]).
Colistimethate (or the sodium salt [colistimethate sodium]) is the inactive prodrug that is hydrolyzed to colistin, which acts as a cationic detergent and damages the bacterial cytoplasmic membrane causing leaking of intracellular substances and cell death.
Absorption: Not absorbed from the GI tract, mucous membranes, or intact skin (Note: GI absorption has been observed in infants).
Distribution:
CSF penetration:
Infants, Children, and Adolescents ≤14 years: Colistin: 3% to 19%; may be increased in the presence of meningitis (Antachopoulos 2010).
Adults: Colistin: ~5% (Markantonis 2009).
Vd:
Neonates (GA: 29 to 41 weeks; PNA: 5 to 15 days): IV: Colistin: 7.7 ± 9.3 L/kg (Nakwan 2016).
Children ≥2 years and Adolescents <15 years: IV: Colistin: 0.6 ± 0.3 L/kg.
Adults:
Healthy volunteer: IV: Colistimethate: 8.92 L; Colistin: 12.4 L (Couet 2012).
Critically ill: IV: Colistimethate: 5.3 to 13.5 L; Colistin: 7.2 to 189 L (Couet 2012).
Cystic fibrosis: IV: Colistimethate: 10.8 to 31.3 L (Li 2003).
Protein binding: 50%.
Metabolism: Colistimethate sodium (inactive prodrug) is hydrolyzed to colistin (active form). Note: Only ~30% of colistimethate sodium is converted to colistin (Couet 2011).
Half-life elimination: IM, IV: All ages: Colistimethate: 2 to 3 hours.
Neonates (GA: 29 to 41 weeks; PNA: 5 to 15 days): IV: Colistin: 9 ± 6.5 hours (Nakwan 2016).
Children ≥2 years and Adolescents <15 years (critically ill): IV: Colistin: 2.6 ± 0.4 hours (Wacharachaisurapol 2020).
Adults:
Critically ill: IV: Colistimethate: 2.3 hours; Colistin: 14.4 hours (Plachouras 2009).
Cystic fibrosis: IV: Colistin: ~4 hours (Li 2003).
End-stage renal disease patients receiving CAPD: IV: Colistin: 13.2 hours (Koomanachai 2014).
Time to peak:
Neonates (GA: 29 to 41 weeks; PNA: 5 to 15 days): IV: Colistin: 1.3 ± 0.9 hours from end of 0.5-hour infusion (Nakwan 2016).
Children ≥2 years and Adolescents <15 years: IV: Colistin: 1.1 ± 0.3 hours from end of 5-minute injection (Wacharachaisurapol 2020).
Adults:
Healthy volunteers: IV: Colistin: 2 hours (range: 1 to 4 hours) (Couet 2011).
Critically ill: IV: Colistin: ~7 hours (Plachouras 2009).
Excretion: Primarily urine (as unchanged drug); most colistin recovered in the urine is from postexcretion hydrolysis of colistimethate sodium (Couet 2011).
Anti-infective considerations:
Parameters associated with efficacy: Concentration dependent; associated with area under the curve (AUC24)/minimum inhibitory concentration (MIC), goal: AUC24 at steady state ~50 mg•hour/L or an average plasma colistin concentration at steady state (Css,avg) of 2 mg/L (Abdul-Aziz 2020; ESCMID/EUCAST [Tsuji 2019]).
Organism specific:
P. aeruginosa: Goal: fAUC0-24/MIC: 6.6 to 13.7 (Abdul-Aziz 2020; Cheah 2015).
A. baumannii: Goal: fAUC0-24/MIC: 3.5 to 17.6 (Abdul-Aziz 2020; Cheah 2015).
Expected drug concentrations in patients with normal renal function:
Note: Reported concentrations are reflective of active colistin component unless otherwise specified.
Cmax (peak):
Neonates (GA: 29 to 41 weeks; PNA: 5 to 15 days): IV: 5 mg colistin base activity (CBA)/kg, single dose: 3 ± 0.7 mg/L (Nakwan 2016).
Children ≥2 years of age and adolescents ≤15 years of age: IV:
1.7 to 2.5 mg CBA/kg, single dose: 4.1 ± 1.3 mg/L (Wacharachaisurapol 2020).
4 mg CBA/kg, single dose: 6.1 ± 2.4 mg/L (Wacharachaisurapol 2020).
Adults:
Healthy volunteers: 2.5 mg/kg CBA IV every 12 hours, steady state: 1.79 ± 0.37 mg/L (Fan 2022).
Patients who are critically ill: 0.875 to 1.58 mg/kg CBA IV every 8 or 12 hours, steady state: 2.93 mg/L (Markou 2008).
AUC (total):
AUC0-24: Neonates (GA: 29 to 41 weeks; PNA: 5 to 15 days): IV: 5 mg CBA/kg, single dose: 21.1 ± 8.1 mg•hour/L (Nakwan 2016).
Adults:
AUC0-12: Healthy volunteers: 2.5 mg/kg CBA IV every 12 hours, steady state: 15.28 ± 3.29 mg•hour/L (Fan 2022).
AUC0-24: Patients who are critically ill: 0.875 to 1.58 mg/kg CBA IV every 8 or 12 hours, steady state: 12.8 mg•hour/L (range: 6 to 20 mg•hour/L) (Markou 2008).
Postantibiotic effect: Bacterial killing may continue after colistin concentration falls below the MIC of targeted pathogen and varies based on the organism, antimicrobial concentration, and duration of antimicrobial exposure:
A. baumannii: 0 to >7 hours (Rasidin 2020).
P. aeruginosa: ~1 to 1.5 hours (Bozkurt-Güzel 2012).
Parameters associated with toxicity: A Cmin > ~2 to 2.4 mg/L has been associated with increased risk of nephrotoxicity (ESCMID/EUCAST [Tsuji 2019]; Forrest 2017; Horcajada 2016; Sorlí 2013).
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