Introduction
Methods
Results and discussion
Year [ref] | Setting | Medication used | Number of patients | Demographics | Dosage of colistin/duration | Nephrotoxicity | Neurotoxicity | Other toxicities | |
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1 | 1962 [26] | Medical wards | Colistimethate sodium (IV) | 48 | Adults: 150 mg q12 h Children: 5 to 10 mg/kg/day. Duration: at least 10 days | 12 pts had transient mild elevation of BUN (average increase 14 mg/dl) and returned to normal. 5 pts had prolonged elevation of BUN (average increase 50 mg/dl) and returned to normal | 13/48 pts paresthesias; 3/48 pts ataxia | 3/48 pts pruritus. No drug fever, hepatic or bone marrow toxicity | |
2 | 1963 [19] | Medical wards | Colistimethate sodium (IM) | 1 | 64 year old male | 6.5 mg/kg/day (150 mg q8 h) for 12 days (he received concurrently kanamycin IM for 2 days and after colistin therapy chloramphenicol) | BUN increased from normal baseline values to 44 mg/dl (drug was stopped). The BUN continued to rise and then began to return to normal. Postmortem examination of the kidney revealed findings compatible with drug induced nephrotoxicity | Possible hepatotoxicity | |
3 | 1963 [66] | Medical and surgical wards | Colistimethate sodium (IM and topically) | 62 | Topically: 1% or 2% solution q4h or q12h. Duration (range): 2 to 7 d Intramuscularly (range): 150 to 300 mg/day. Duration (range): 1.5 to 19 d | Topically: no side effects | Topically: no side effects Intramuscularly: 15/55 pts reported one or more of the following: lethargy, dizziness, nausea, confusion, slurred speech, numbness, paresthesias, pruritus, pain at the injection | Topically: no side effects | |
4 | 1963 [20] | Medical wards | Colistimethate sodium (IM) | 11 | Dosagea: 1.5 MIU q12h for a week and continued for a further week if the pt was improving (2 pts received 2 MIU q8h for 5 days and then 3 MIU q8h) | No renal toxicity | 2 pts trigeminal paresthesia | 1 pt developed follicular rash of the face | |
14 | Dosage (range): 1 MIU q12h to 1.5 MIU q8 h for 7 or more days | ||||||||
5 | 1964 [28] | Medical wards | Colistimethate sodium (IV) | 8 | Age (range): 25 to 69 years | Dosage: 2 to 2.5 mg/kg q12 h. Duration (range): 8 to 14 days. | 4/8 pts fall in creatinine clearance (range: 16.5 to 38 ml/min) and increase in serum creatinine (range: 0.2 to 2 mg/dl) | No neurotoxicity | No pruritus |
6 | 1964 [21] | Children's hospital | Colistimethate sodium (IM) | 36 new-borns | Age (range): 6 hours to 12 days | Dosage (range): 2.5 to 5 mg/kg/day in 2 to 4 doses. Total dose (range): 10 to 240 mg (1 new-born (3.3 kg) received 160 mg of colistin (overdosage) in 7 days) | 16 pts had renal epithelial tubular cells on urinalyses; 14 pts had urinary protein excretion | No neurotoxicity | |
7 | 1964 [22] | Medical wards | Colistimethate sodium (IM) | 1 | 50 year old male | Dosage: 300 mg/day for 5 days, then 200 mg/day for 4 days | Urinary retention, rise in blood urea nitrogen | Difficulty in breathing, dysphagia, generalized weakness, hallucinations, apnea requiring intubation | |
8 | 1965 [50] | Medical wards | Colistimethate sodium (IM) | 1 | 66 year old female with azotemia | Dosage: 150 mg q 12 h for 8 days. Cumulative dose: 2,550 mg | 7th day of colistin: circumoral paresthesias; 8th day: vomiting, difficulty in breathing, moving, speaking, and became apneic; 10th day: grand mal seizures followed by transient right facial and arm weakness | ||
9 | 1965 [24] | Medical wards | Colistimethate sodium (IM) | 17 (19 courses) | Age (range): 33 to 90 years | Total cumulative dose (range): 0.56 gr to 2.4 gr | 8 pts dizziness – vertigo (1 pt discontinued), 5 pts oral paresthesias | 3 pts pain at site of injection, 3 pts nausea/vomiting, 2 pts pruritus/rash | |
10 | 1965 [23] | Medical wards | Colistimethate sodium (IM) | 1 | 75 mg q12 h | Episodes of ptosis, muscular weakness of the face and of the extremities | |||
11 | 1965 [25] | Medical wards (renal department) | Colistimethate sodium (IM) | 25 | 12 males, 13 females. Age (range): 14 to 66 years. All with impaired renal function | Dosage (range): 2 MIU to 4.4 MIU/day. Duration (average): 8.5 days | 9/25 pts had an increase in plasma creatinine levels | ||
12 | 1966 [46] | Medical wards | Colistimethate sodium (IM) | 1 | 47 year old female | 100 mg q8h | Perioral paresthesia, numbness in the hands, weakness, ataxia, lightheadedness, shortness of breath, apnea | Nausea, itching of the face, hands, and arms (no visible rash) | |
13 | 1966 [67] | Medical wards | Colistimethate sodium (IM) | 21 | All had urinary tract abnormalities or had undergone prostatectomy | Dosage: 120 mg (1.5 MIU) q8h for 7 days | No constant effect on creatinine clearance was observed | ||
14 | 1966 [43] | Medical wards | Colistimethate sodium (IM) | 4 who developed acute renal failure | Age (range): 41 to 75 years. All with pre-existing renal disease | Dosage: 5 to 6.3 mg/kg/day. Duration (range): 3 to 12 days | Acute tubular failure (3 pts acute tubular necrosis, 1 pt recovered) | Retrosternal discomfort 1 pt | |
15 | 1966 [48] | Medical wards | Colistimethate sodium (IM) | 1 | 48 year old female | 75 mg q12h (she also received chloramphenicol 500 mg q6h po) | Diplopia and bilateral eye ptosis, weakness of neck flexion, difficulty in raising her arms | ||
16 | 1966 [51] | Department of anaesthesiology | Colistimethate sodium (IM) | 1 | 49 year old female with nephrolithiasis | 75 mg q12 h (she also received chloramphenicol 500 mg q4h po and sulfisoxazole 1 g q4h po) | Post-operative apnea | ||
17 | 1967 [27] | Medical and surgical wards | Colistimethate sodium (IV) | 23 | Males, moderately to severely ill | Dosage (range): 1.1 to 5 mg/kg/day q12h for 6 to 7 days (in 2 cases the treatment was discontinued after 2 and 3 days) | 6/23 pts renal impairment; 7/23 pts albuminuria | 1 pt circumoral paresthesia | 5/23 pts mild itching |
18 | 1968 [44] | Medical wards | Colistimethate sodium (IV) | 7 | Age (range): 28 to 48 years. 4 females, 3 males; all had terminal and irreversible renal failure | 2 to 3 mg/kg (1 dose) | 2 pts mild dizziness and instability | ||
19 | 1968 [56] | Medical wards | Colistin sulfate (PO) | 93 (48 cases E. coli and 45 cases Shigella spp.) | E. coli : 100,000 IU/kg/day in adults and 150,000 IU/kg/day in children for 7 days Shigella: 200,000 IU/kg/day in adults and 300,000 IU/kg/day in children for 8 to 10 days | No toxic symptoms | No toxic symptoms | 1 pt generalized rash, 1 pt vomiting | |
20 | 1968 [49] | Medical wards (respiratory care unit) | Colistimethate sodium (IM) and Polymyxin B (IM or IV) | 11 | Age (range): 36 to 74 years. 4 females, 7 males; all had acute or chronic renal disease | Dosage of colistimethate sodium (range): 100 to 400 mg/day. Duration (range): 1 to 29 doses or 1 to 15 days. Dosage of polymyxin B: 50 mg (1 dose) IM (1 pt) and 100 mg (1 dose) IV (1 pt) | All pts at their admission had apnea that recovered in all cases. Paresthesias 2 pts, diplopia 3 pts, difficulty in swallowing 3 pts, ptosis 2 pts, generalized weakness 3 pts, blurring of vision 1 pt, slurred speech 1 pt, lethargy 1 pt, coma 1 pt | ||
21 | 1969 [42] | Medical wards | Colistimethate sodium (IV) | 1 | 14 year old male with acute leukemia | Dosage: 5 mg/kg/day for 5 days, then increased to 7 mg/kg/day on day 6, 10 mg/kg/day on day 7, and 17 mg/kg/day on day 9. Duration: 14 days | Acute tubular necrosis | ||
22 | 1969 [29] | Medical wards (pediatrics) | Colistimethate sodium (IM) | 1 | 4 year old female with appendicitis | Dosage: 30 mg/kg q6h (total dose received 1,050 mg during 42 h | Acute renal failure | Neuromyal hyperactivity, seizure-like episodes, uncoordination, disorientation, flaccid quadriplegia, respiratory arrest, apnea | |
23 | 1970 [4] | Medical and surgical wards | Colistimethate sodium (IM) | 288 (317 courses) | 205 courses received a total of <1 gr, 69 courses 1 to 2 gr, 43 courses > 2 gr. All courses were administered IM q12 h | Total: 64/317 courses (renal insufficiency 63 pts, acute tubular necrosis 6 pts, hematuria 1 pt) | Total: 23/317 courses (paresthesias 15 pts, respiratory insufficiency and apnea 6 pts, nausea and vomiting 4 pts, dizziness 3 pts, muscular weakness 2 pts, peripheral neuropathy, confusion, psychosis, convulsive seizure 1 pt each) | Total allergic reactions: 7/317 (drug fever 3 pts, eosinophilia 2 pts, macular eruption 2 pts, urticarial eruption 1 pt) | |
24 | 1970 [68] | Medical wards and ICU | Colistimethate sodium (aerosol) | 20 | Age (range): 23 to 81 years | Group 1: 50 mg q8h for 7 days. Group 2: 100 mg q8h for 7 days | No toxic symptoms | 1 pt experienced palpitations and a sensation of chest tightness (treatment was discontinued) | |
25 | 1970 [3] | Department of pediatrics | Colistimethate sodium (IM) | 1 | Age: 10 months (male) | 15 mg q6 h (2 doses) and then 250 mg (38.5 mg/kg) (3 dose) | Acute renal failure | No neurotoxicity | |
26 | 1970 [30] | ICU, neurosurgical department | Colistimethate sodium (IV, IM, and aerosol) | 14 | Age (range): 31 to 71 years | Mean duration: 9.7 days. Dosage: 26 MIU/day: 10 MIU IM, 10 MIU IV, and 6 MIU aerosol | In all pts a considerable fall in creatinine clearance and rises in blood urea and serum creatinine levels were observed. 5 pts developed acute tubular necrosis (histological confirmed). In 6 pts renal function returned to normal | ||
27 | 1970 [69] | Department of renal disease | Colistimethate sodium (route of administration not reported) | 1 | 41 year old | Duration: 7 days. Dose: 6.3 mg/kg/day | Severe oliguric renal failure | ||
28 | 1970 [31] | Department of pediatrics | Colistimethate sodium (IM) | 1 | 3 year old | 150 mg q8h (she received 3 injections) | No renal toxicity | No neurotoxicity | |
29 | 1970 [32] | Medical wards (urology department) | Colistimethate sodium (IM) | 1 | 33 year old male with a solitary kidney | 25 mg q6h for 5 days and 250 mg q6h for 1 day | Increase in serum creatinine levels compared to baseline levels (1.1 mg/dl to 3 mg/dl) Returned to approximately normal values after 6 months | Muscular weakness, generalized paresthesias, speech disturbances, ptosis, hypotonia, areflexia, ataxia, difficulty in breathing | |
30 | 1971 [47] | Department of neurology | Colistimethate sodium (IM) | 1 | 70 year old male with myasthenia gravis | 150 mg (one injection) | 2 hours after the injection: muscular weakness; 30 minutes later he developed respiratory arrest | ||
31 | 1971 [70] | Department of respiratory diseases | Polymyxin B (aerosol) | 2 | Case 1: 51 year old female. Case 2: 57 year old male | Case 1: 15 mg Case 2: 10 mg | Case 1: pruritus, nausea, flashing, dyspnea Case 2: acute respiratory acidosis | ||
32 | 1973 [33] | Medical wards (Hemodialysis Centre) | Colistimethate sodium (IM) | 2 | Case 1: 16 year old female. Case 2: 23 year old female | Case 1: 150 mg q6h 1st day, 150 mg q4h 2nd day (20 mg/kg/day) Case 2: 180, 240, 180, 120 mg in divided doses on 1st, 2nd, 3rd, 4th day, respectively | Both pts developed acute renal failure | Case 1: neuromuscular blockade that resulted in quadriplegia, apnea, cardiac arrest Case 2: circumoral – acral paresthesias | |
33 | 1974 [71] | Medical wards | Colistimethate sodium (IM) | 1 | 66 year old male | 6 MIU/day for 60 days | No renal toxicity | Total ophthalmoplegia, flaccid paralysis of both upper limbs, reduced speech fluency, difficulty in finding words, apathy | |
34 | 1977 [34] | Department of pediatrics | Colistimethate sodium (IM) | 1 | 5 year old male | 200,000 IU/kg/day for 8 days | Acute oliguric renal failure | Muscular weakness, speech disturbances |
Year [ref] | Setting | Medication used | Number. of patients | Demographics | Dosage of colistin/duration | Definition of nephrotoxicity | Nephrotoxicity | Neurotoxicity | Other toxicities | |
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1 | 1995 [57] | Department of dermatology | Colistin sulfate (ointment/topically) | 1 | 45 year old | 50,000 IU for 10 days | Edematous eczema | |||
2 | 1998 [58] | Department of dermatology | Colistimethate sodium (ophthalmic solution) | 1 | 4 year old male with bilateral ocular prosthesis | After 3 weeks he developed itchy erythematous eruptions on both periorbital areas | ||||
3 | 1999 [72] | Neurosurgical wards | Colistimethate sodium (intraventricular) | 2 | 16 year old male and 34 year old female | Case 1: 5 mg (62,500 IU) q12h for 19 days Case 2: 5 mg (62,500 IU) q12h for 5 days then 10 mg (125,000 IU) q12h for 12 days | No adverse reactions | |||
4 | 1999 [8] | ICU (52%), transplant unit (13%), surgical and medical wards (35%) | Colistimethate sodium (IV) | 59 (60 cases) | Mean age: 42.1 years. Mean (± SD) APACHE II: 13.1 (± 7.0) | Mean duration: 12.6 d (2 to 34 d). Mean daily dose: 152.8 mg (approximately 2 MIU) (60–300 mg) | 22 pts (37%; 11/41 with normal baseline renal function had worsening during treatment (mean increase in serum creatinine 0.9 ± 0.6 mg/dl) and 11/19 with abnormal baseline renal function had worsening during treatment (mean increase in serum creatinine 1.5 ± 1.4 mg/dl)). Nephrotoxicity did not cause discontinuation | No neuromuscular disorders | ||
5 | 2000 [73] | Medical wards | Colistimethate sodium (aerosol) | 3 | 67 year old male, 45 year old male, 59 year old male | 150 mg (2 MIU) q12h for 13 days, 100 mg (approximately 1.5 MIU) q12h for 14 days, 150 mg (2 MIU) q12h for 11 days | No nephrotoxicity | No hematological toxicity | ||
6 | 2002 [74] | Neurosurgical wards | Colistimethate sodium (IV) | 1 | 14 year old male | 1 MIU q6h for 30 days | No adverse reactions | |||
7 | 2003 [10] | Abdominal organ transplantation ICU | Colistimethate sodium (IV) | 23 (20 had received organ transplantation, 3 abdominal surgery) | Mean age: 52 years | Mean duration: 17 days (7 to 36 days) | Renal failure was defined by a requirement either for intermittent hemodialysis or for continuous venous hemofiltration | 1/2 pts developed renal failure requiring artificial kidney support (the other 21 pts were already receiving artificial kidney support) | 1 pt diffuse muscular weakness (resolved after discontinuation) | |
8 | 2003 [11] | ICU | Colistimethate sodium (IV) | 24 with sepsis, 26 courses of colistin | Mean age: 44.3 years. Mean APACHE II: 20.6 | Mean duration: 13.5 days (4 to 24 days). Dosage: 3 MIU q8h | Renal failure was defined as an increase in serum creatinine >1 mg/dl during treatment | 3 pts (14.3%). Only 1 pt required continuous venovenous hemodiafiltration | No clinically apparent neuromuscular transmission blockade | |
9 | 2003 [36] | Tertiary care hospital | Polymyxin B (parenterally) | 60 receiving polymyxin B | Mean age: 61 years | Mean duration: 13.5 days (1 to 56 days). Mean daily dose: 1.1 MIU | Renal failure was defined as doubling of serum creatinine value of ≥ 2.0 mg/dl | 7/50 pts (14%) | ||
10 | 2003 [74] | ICU | Colistimethate sodium (IV) | 35 (21 received colistin (CO group) and 14 imipenem (IM group)) | Mean age: CO group 56.9 years, IM group 64.5 years. Mean APACHE II: CO group 19.6, IM group 20.5 | CO group: mean duration 14,7 days (10 to 21 days). Dosage: 2.5 to 5 mg/kg/day | In patients with normal renal function (creatinine <1.2), renal failure was defined as creatinine value >2 mg/dl, as a reduction of creatinine clearance of 50% relative to antibiotic initiation, or need for renal replacement therapy. In patients with normal renal function, renal failure was defined as increase of 50% of the baseline creatinine level, as a reduction of creatinine clearance of 50% relative to antibiotic initiation, or need for renal replacement therapy | 5/21 pts (24%; CO group), 6/14 pts (42%; IM group) | ||
11 | 2004 [75] | ICU | Colistimethate sodium (IV) | 1 | 41 year old male | 2 MIU/day continuous infusion | No adverse reactions | |||
12 | 2004 [76] | ICU | Colistimethate sodium (IV) | 1 | 48 year old male | 9 MIU/day (2.5 mg/kg/day) for 15 days | No adverse reactions | |||
13 | 2004 [37] | Tertiary care hospital, ICU (92%) | Polymyxin B (IV) | 25 (29 courses: 21 IV, 6 aerosol, 2 combination) | Mean age: 55 years. Mean APACHE II: 21 | Loading dose on day 1 with 2.5 to 3 mg/kg IV polymyxin B. Aerosolized: approximately 2.5 mg/kg/day (approximately 1.75 MIU). Mean duration: 19 d (2 to 57 d) | Nephrotoxicity was defined as the doubling of serum creatinine during therapy | 3/29 courses (10%) | 2/29 courses (7%) onset of seizures and neuromuscular weakness possibly related to polymyxin B | |
14 | 2005 [12] | ICU | Colistimethate sodium (IV) | 43 | Mean age: 56.5 years. APACHE II: 25.8 ± 3.7 | 3 MIU q8h | Acute renal failure was defined as a rise of ≥ 2 mg/dl in serum creatinine level in patients with previously normal renal function. In patients with a history of renal insufficiency, acute on chronic renal failure was defined as at least doubling of the baseline serum creatinine level (defined as the creatinine level at the initiation of colistin treatment) | 8/43 pts (18.6%; 3/35 pts with normal renal function (8.6%) and 5/8 pts with chronic renal failure (62.5%)) | No paresthesias, vertigo, muscle weakness, or apnea were observed | |
15 | 2005 [77] | ICU (84%), medical (11%), surgical (5%) | Colistimethate sodium (aerosol, IV, IM, intrathecal) | 80 (85 courses: 71 aerosol, 12 IV or IM, 2 intrathecal) | Mean age: 57 ± 15 years | Mean duration of aerosol: 12 ± 8 d. Mean duration of IV or IM: 11 ± 6 d. Mean duration of intrathecal: 8 d and 10 d | Nephrotoxicity was defined as a serum creatinine increase of 50% or 1 mg/dl with respect to the baseline level during treatment | 12 courses of IV or IM were recorded. Mean ± SD baseline serum creatinine: 1.25 ± 0.79 mg/dl. Mean ± SD final serum creatinine: 1.20 ± 0.64 mg/dl. Mean ± SD baseline BUN: 8.95 ± 8.96 μmol/l. Mean ± SD final BUN: 8.39 ± 8.06 μmol/l | ||
16 | 2005 [38] | Mainly ICU pts | Colistimethate sodium (IV) | 17 (19 courses) | Median age: 51 years. Median APACHE II: 14 | Mean ± SD duration: 43.4 ± 14.6 days. Mean ± SD daily dose: 4.4 MIU (352 mg) ± 2.1 MIU (168 mg) | Renal failure was defined as an increase more than 50% of the baseline creatinine level to a value higher than 1.3 mg/dl or as a decline in renal function requiring renal replacement therapy | Median baseline serum creatinine: 0.6 mg/dl. Slight increase of the median of values of creatinine at the end by 0.1 mg/dl. Median baseline BUN: 42 mg/dl. Median final BUN: 41 mg/dl. 1 pt had an increase of more than 50% of the baseline creatinine level to a value higher than 1.3 mg/dl at the end of colistin treatment | No apnea or other evidence of neuromuscular blockade. 1 pt polyneuropathy (improved after the end of colistin treatment) | No hepatobiliary toxicity |
17 | 2005 [35] | ICU (80%), medical and surgical wards (20%) | Colistimethate sodium (IV) | 50 (54 episodes) | Mean age: 59.2 years. Mean APACHE II: 16.1 | Mean duration: 21.5 days. Mean daily dose: 4.5 MIU | Renal failure was defined as an increase more than 50% of the baseline creatinine level to a value higher than 1.3 mg/dl or as a decline in renal function requiring renal replacement therapy | 4/50 pts (8%) | 1 pt polyneuropathy (not confirmed) resolved without discontinuation | |
18 | 2005 [78] | ICU | Colistimethate sodium (aerosol) | 8 | Mean age: 59.6 years. Mean APACHE II: 14.6 | Dosage (range): 1.5 to 6 MIU/day. Duration (mean): 10.5 days | Worsening of renal function: 1 pt | No neurotoxicity | ||
19 | 2005 [79] | ICU | Colistimethate sodium (IV) | 1 | 57 year old male | 250 mg q6h for 4 days | Acute renal failure (on the 4th day of colistin therapy) | |||
20 | 2005 [80] | Neurosurgical wards | Colistimethate sodium (intraventricular) | 1 | 23 year old female | 125,000 IU q12h for 3 weeks | No adverse reactions | |||
21 | 2005 [81] | ICU | Colistimethate sodium (IV) | 55 | Mean age: 40 ± 16 years. Mean APACHE II: 21 ± 7 | Duration (mean): 13 ± 5 days | Renal failure was defined as a serum creatinine value of 2 mg/dl or higher, as a reduction in creatinine clearance of 50% compared to therapy initiation, or as a decline in renal function that prompted renal replacement therapy | No adverse reactions. Mean creatinine levels before treatment: 2.3 ± 0.5 mg/dl. Mean creatinine levels after treatment: 2.5 ± 0.6 mg/dl | ||
22 | 2005 [82] | ICU | Colistin (IV) | 1 | 35 year old male | 6 MIU/day for 12 days, 3 days, and 1 day | Acute renal failure occurred at the 2nd and 3rd introduction of colistin. Renal function returned to normal values within 3 and 5 days after colistin withdrawal | |||
23 | 2005 [83] | ICU | Colistimethate sodium (IV) | 14 | Mean age: 49 years | Mean dose: 6 MIU/day. Mean duration: 12 days | 1 pt experienced deterioration of renal function (serum creatinine up to 2.8 mg/dl) | |||
24 | 2005 [84] | ICU, medical wards | Colistimethate sodium (aerosol) | 21 | Mean age: 60.6 ± 15 years. Mean APACHE II: 23.1 ± 9.1 | 19 pts received 2 MIU/day, 1 pt 3 MIU/day, and another pt 4 MIU/day. Median duration: 14 days | Renal failure was defined as a decrease in the estimated creatinine clearance rate of 50%, compared with the rate at the start of therapy, or a decline in renal function that necessitated renal replacement therapy | No episodes of acute renal failure | No symptoms of neurotoxicity | 1 pt experienced bronchospasm that resolved on discontinuation of colistin therapy |
Nephrotoxicity
Incidence
Mechanisms
Clinical manifestations
Risk factors
Treatment
Neurotoxicity
Incidence
Mechanisms
Clinical manifestations
Risk factors
Treatment
Other adverse events
Incidence
Mechanisms
Clinical manifestations
Risk factors
Treatment
Adverse events related to aerosolised colistin
Prevention of adverse events
Overdoses
Drug interactions
Conclusion
Key messages
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Polymyxins are valuable antibiotics for use in patients in the intensive care setting.
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Polymyxins have been recently re-introduced in clinical practice for the treatment of patients with multidrug-resistant Gram-negative bacterial infections.
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Nephrotoxicity and neurotoxicity represent the major adverse effects of polymyxins.
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Data from the recent literature suggest that the use of polymyxins is associated with lower and less severe toxicity compared to that reported in the old literature.
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Caution is needed when polymyxins are administered, particularly in patients with renal dysfunction.