Table 1.
Old studies (from 1962 to 1977) reporting data on polymyxin-induced toxicity in patients without cystic fibrosis
| Year [ref] | Setting | Medication used | Number of patients | Demographics | Dosage of colistin/duration | Nephrotoxicity | Neurotoxicity | Other toxicities | |
| 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 |
a1 mg of colistimethate sodium is approximately equal to 12,500 IU. BUN, blood urea nitrogen; ICU, intensive care unit; IM, intramuscularly; IV, intravenously; MIU, million international units; po, per os; Pt(s), patient(s); ref, reference.