Note: 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) (EMA 2014; ESCMID/EUCAST [Tsuji 2019]; Falagas 2006; Kassamali 2013; Nation 2014; Nation 2017).
|
Colistimethate Sodium |
Colistimethate Sodium |
Colistin-Base Activity (CBA) |
|
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 |
Bronchiectasis, pulmonary colonization/infection with susceptible organisms in cystic fibrosis and noncystic fibrosis patients (off-label use/route): Inhalation: 30 to 150 mg CBA via nebulizer 1 to 2 times daily (maximum dose: 150 mg CBA 2 times daily) (Haworth 2014; Le 2010; Sabuda 2008; Steinfort 2007). Note: An optimal dosing regimen has not been determined and varies widely among studies; lower doses have been used in noncystic fibrosis patients with bronchiectasis (Steinfort 2007). Use in addition to systemic antibiotics (ESCMID/EUCAST [Tsuji 2019]).
Meningitis and ventriculitis (susceptible gram-negative organisms; adjunct to systemic therapy) (use a preservative-free preparation): Intrathecal/intraventricular (off-label route): 4.2 mg CBA/day (equivalent to 10 mg CMS/day) (ESCMID/EUCAST [Tsuji 2019]; IDSA [Tunkel 2017]; Imberti 2012; Ziaka 2013). Note: Dose in clinical reports has ranged from 0.7 to 8.3 mg CBA/day in 1 or 2 divided doses (administered with concomitant systemic antimicrobial therapy) (Benifla 2004; De Bonis 2016; Falagas 2007; Fotakopoulos 2016; Imberti 2012; Katragkou 2005; Rodríguez Guardado 2008). When intraventricular colistimethate is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF) (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Intraventricular administration is generally reserved for use in patients who fail parenteral therapy despite removal of CSF shunt or when CSF shunt cannot be removed (Baddour 2018).
Pulmonary infection due to multidrug-resistant gram-negative bacilli (eg, P. aeruginosa, Acinetobacter spp.) (adjunctive agent) (off-label route): Inhalation for nebulization: Dose not well defined: 75 to 150 mg CBA every 12 hours (Doshi 2013; Rattanaumpawan 2010; Valachis 2015); doses up to 167 mg every 8 hours have been described (Lu 2012); however, doses are typically rounded to the nearest vial size. Note: Use in combination with systemic antimicrobial therapy (ESCMID/EUCAST [Tsuji 2019]; IDSA/ATS [Kalil 2016]).
Systemic infections (eg, bacteremia, intra-abdominal infections, meningitis, pneumonia [hospital acquired or ventilator associated], sepsis) due to multidrug-resistant gram-negative bacilli [eg, P. aeruginosa, Acinetobacter spp.]) (alternative agent):
Note: Polymyxin B is preferred over CMS due to significant interpatient variability in pharmacokinetics, slower attainment of desired plasma concentrations, and increased risk of nephrotoxicity with CMS (ESCMID/EUCAST [Tsuji 2019]; IDSA [Tamma 2021]). To minimize development of resistance, use in combination with other antibiotics, depending on infection site and susceptibilities (Bergen 2015; ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015).
IV: 300 mg CBA loading dose followed by 150 to 180 mg CBA twice daily as maintenance starting 12 hours after the loading dose (Dalfino 2012; ESCMID/EUCAST [Tsuji 2019]; Plachouras 2009). Note: This dosing is designed to target average colistin steady-state plasma concentration of 2 mg/L and is derived from analysis of pharmacokinetic data in critically ill patients (Nation 2017).
Urinary tract infection due to multidrug-resistant gram-negative bacilli (eg, P. aeruginosa, Acinetobacter spp.): Note: CMS is preferred for treatment of lower urinary tract infections because of higher urinary concentrations compared to polymyxin B (ESCMID/EUCAST [Tsuji 2019]; IDSA [Tamma 2021]). To minimize development of resistance, may use in combination with other antibiotics, depending on susceptibilities (Bergen 2015; ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015).
IV: 300 mg CBA loading dose followed by 150 to 180 mg CBA twice daily as maintenance starting 12 hours after the loading dose (Dalfino 2012; ESCMID/EUCAST [Tsuji 2019]; Plachouras 2009). Note: This dosing is designed to target average colistin steady-state plasma concentration of 2 mg/L and is derived from analysis of pharmacokinetic data in critically ill patients (Nation 2017).
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 (EMA 2014; Falagas 2006; Kassamali 2013; Nation 2014; Nation 2017). 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 (Nation 2017). 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 (expert opinion).
Altered kidney function:
Loading dose: IV: 300 mg CBA, followed by a maintenance dose based on CrCl (ESCMID/EUCAST [Tsuji 2019]; Nation 2017), calculated using the Cockcroft-Gault equation with an adjusted body weight (ideal body weight [IBW] + 0.4 [total body weight – IBW]) (ESCMID/EUCAST [Tsuji 2019]; Nation 2017; Winter 2012).
Maintenance dose: IV: The following total daily maintenance doses (administered in 2 divided doses) are recommended (ESCMID/EUCAST [Tsuji 2019]; Nation 2017); 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 (EMA 2014; Nation 2016):
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 (Bilbao-Meseguer 2018; Udy 2010)
IV: 360 mg CBA/day (expert opinion).
Note: No definitive studies have evaluated colistin pharmacokinetics in ARC. Patients with ARC receiving conventional doses required longer treatments than those without ARC (Aitullina 2019).
Hemodialysis, intermittent (thrice weekly): Dialyzable (~30%) (Jitmuang 2017):
Loading dose: IV: 300 mg CBA (Nation 2017; Tsuji 2019).
Maintenance dose: IV:
Dialysis days: 180 mg CBA on dialysis days (administer after dialysis) (ESCMID/EUCAST [Tsuji 2019]; Nation 2017; expert opinion).
Nondialysis days: 130 mg CBA on nondialysis days (ESCMID/EUCAST [Tsuji 2019]; Nation 2017).
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 (Koomanachai 2014).
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 (ESCMID/EUCAST [Tsuji 2019]). 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 (ESCMID/EUCAST [Tsuji 2019]; Karaiskos 2016; Karvanen 2013).
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 (ESCMID/EUCAST [Tsuji 2019]; Nation 2017).
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 (ESCMID/EUCAST [Tsuji 2019]; Nation 2017).
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Colistin (colistimethate): Pediatric drug information")
Note: 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 (EMA 2014; Falagas 2006; Kassamali 2013; Nation 2017).
General dosing, susceptible infection: Infants, Children, and Adolescents: Colistin base: IM, IV: 2.5 to 5 mg CBA/kg/day divided every 6 to 12 hours
CNS infection (VP-shunt infection, ventriculitis, meningitis), multidrug resistant: Limited data available; variable doses reported; optimal dose not defined.
Infants and Children: Very limited data available: Intraventricular/Intrathecal: Colistin base: Reported range: 1 to 4.2 mg CBA/dose once daily in combination with systemic antibiotics (Dalgic 2009; IDSA [Tunkel 2017]; Ng 2006; Ozdemir 2010). Doses should be individualized based on culture/sensitivity, MIC, and tolerability while ensuring that patient size and CSF volume are considered. In one case report, a 4-year old with multidrug resistant Acinetobacter baumannii received an intraventricular dose of 1 mg CBA on Day 1, followed by 2 mg CBA once daily for 2 days, then 4 mg CBA once daily; after 13 days, a dose reduction to 2 mg CBA once daily was necessary due to CSF leukocytosis (Ng 2006). A similar protocol was described in a 2-month old with multidrug resistant Acinetobacter baumannii; the initial dose on Day 1 was 1 mg CBA followed by 2 mg CBA once daily for 2 days, then 4 mg CBA once daily; due to failure to sterilize the CSF, the dose was slowly titrated up to 10 mg CBA/day for a total of 20 days (Dalgic 2009). In a case report of a 3-year old with multidrug resistant Acinetobacter baumannii, intrathecal colistin was administered without titration at a dose of 4.2 mg CBA/day (Ozdemir 2010).
Adolescents: Very limited data available: Intraventricular/Intrathecal: Colistin base: 4.2 mg CBA/day (equivalent to 10 mg CMS/day) (IDSA [Tunkel 2017]; Yagmur 2006); Note: Dose in clinical reports in adults has ranged from 0.7 to 8.3 mg CBA/day in 1 or 2 divided doses (administered with concomitant systemic antimicrobial therapy) (Benifla 2004; Falagas 2007; Imberti 2012; Katragkou 2005)
Cystic fibrosis, pulmonary infection: Limited data available: Children ≥5 years and Adolescents: Colistin base: IV: Usual reported range: 3 to 5 mg CBA/kg/day divided every 8 hours; maximum dose: 100 mg CBA/dose (Bosso 1991; Reed 2001; Young 2013); doses >5 mg CBA/kg/day (up to 8 mg CBA/kg/day) may be required in some situations; however, higher doses are associated with more severe toxicity (Bosso 1991; Reed 2001).
Pulmonary infection: Limited data available: Infants, Children, and Adolescents: Colistin base: Inhalation: Usual dose: 75 to 150 mg CBA in 3 mL of NS (4 mL total volume) via nebulizer twice daily is most frequently reported in clinical practice; reported range: 30 to 150 mg CBA/dose (Le 2010; Tramper-Stranders 2010)
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.
Refer to adult dosing.
CNS toxicity: Dose reduction may reduce neurologic symptoms.
Nephrotoxicity: Withhold treatment if signs of renal impairment occur during treatment.
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
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 (ESCMID/EUCAST [Tsuji 2019]).
Inhalation (off-label route): Administer solution via nebulizer (vibrating plate nebulizer may be preferred [Lu 2012]) 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 (Le 2010). 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 (Lu 2012).
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 (FDA 2007; McCoy 2007; Wallace 2008). 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 (Healan 2012; Wallace 2008). Storing for >24 hours may increase the risk for potential lung toxicity; preparation immediately prior to administration is recommended (FDA 2007; Le 2010, Wallace 2008).
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 (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
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 30 minutes.
Continuous IV infusion: Initially, one-half of the total daily dose is administered by direct IV injection over 3 to 5 minutes followed 1 to 2 hours later by the remaining one-half of the total daily dose diluted in a compatible IV solution infused over 22 to 23 hours. Infusion should be completed within 24 hours of preparation.
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 (Le 2010).
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 (FDA 2007; McCoy 2007; Wallace 2008). 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 (Healan 2012; Wallace 2008). Storing for >24 hours may increase the risk for potential lung toxicity; preparation immediately prior to administration is recommended (FDA 2007; Le 2010; Wallace 2008).
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, experts recommend the drain be clamped for 15 to 60 minutes to allow equilibration of colistin with CSF prior to opening the drain (Tunkel [IDSA 2017).
Treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli (particularly Pseudomonas aeruginosa) which are resistant to other antibacterials or in patients allergic to other antibacterials
Bronchiectasis, pulmonary colonization/infection with susceptible organisms in cystic fibrosis and noncystic fibrosis patients (nebulized); Cystic fibrosis; Pneumonia, hospital-acquired or ventilator-associated due to multidrug-resistant gram-negative bacilli (eg, Pseudomonas aeruginosa or Acinetobacter baumannii [nebulized]) (alternative agent)
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.
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; monitor closely.
• Renal toxicity: Dose-dependent nephrotoxicity has been reported, generally reversible upon discontinuation of treatment. Withhold treatment if signs of renal impairment occur during 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.
• Appropriate use: IV: Use only to prevent or treat infections strongly suspected or proven to be caused by susceptible bacteria to minimize development of bacterial drug resistance.
• 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.
Nephrotoxicity is dose dependent and reversible upon discontinuation and has been observed to occur within the first 4 days of therapy in patients with cystic fibrosis (Bosso 1991). The Cystic Fibrosis Foundation recommends that patients not use colistimethate for inhalation premixed by pharmacies; patients should prepare their colistimethate nebulizer inhalation solutions immediately prior to use. Colistin is comprised of two components: Colistin A (polymyxin E1) and colistin B (polymyxin E2). Polymyxin E1 has been shown to cause localized airway inflammation in animal studies and may result in lung toxicity in humans. Clinicians who continue to prescribe colistimethate for inhalation should be aware of this potentially life-threatening effect and should administer solutions for inhalation promptly following preparation of solution.
None known.
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
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
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
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. 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
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: May enhance the neuromuscular-blocking effect of Colistimethate. Risk C: Monitor therapy
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: ~5% (Markantonis 2009).
Vd:
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: Adolescents and Adults: 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: Colistimethate: 2 to 3 hours.
Critically ill: Infants (including premature infants), Children, Adolescents, and Adults: 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:
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).
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
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