colistin belongs to the polymyxin class of antibiotics which is a group of cationic polypeptides . however , the popularity rapidly faded in 1970s because of significant renal and neurological toxicity and was replaced with less toxic antibiotics with a comparable or broader antibacterial spectrum such as aminoglycosides . with the recent emergence of multi drug - resistant ( mdr ) gram - negative organisms , in particular pseudomonas aeruginosa , acinetobacter baumannii , and klebsiella pneumonia , colistin has been reconsidered as a potential therapeutic agent for the past 10 - 15 years . this has not only increased the clinical usage of this ancient drug , but has also increased the prevalence of all the toxicities related to colistin . neurotoxicity is the second most common toxicity after nephrotoxicity following colistin therapy . among the various manifestations of its neurotoxicity , several cases of respiratory failure due to colistin were reported in the previous era . however , a 31-year - old white female with history of spina bifida , paraplegia , hydrocephalus status post ventriculo - peritoneal shunt , osteomyelitis of the left hip status post left leg amputation , and chronic sacral decubitus ulcer presented with foul smelling discharge from her sacral wound for 2 weeks . the culture from the wound grew two biotypes of pseudomonas aeruginosa : one was resistant to all antibiotics except for colistin while the other was resistant to all antibiotics except for colistin and imipenem . in addition , methicillin - resistant staphylococcus aureus ( mrsa ) grew from the intraoperative bone culture . she was started on colistimethate sodium ( cms ) 200 mg intravenously every 12 hours for her mdr p. aeruginosa . she was then discharged to a sub - acute rehabilitation center on cms and vancomycin . after three days , she was noted to have sudden respiratory distress in the sub - acute rehabilitation center for which emergency medical service ( ems ) was called . on arrival she was immediately started on bag - valve mask ventilation ( bvm ) and was taken to the emergency room ( er ) . in the er , she was noted to have oxygen saturation at 80s on bvm and was emergently intubated . shortly after resuscitation , her arterial blood gas analysis revealed ph of 7.45 , paco2 of 25 , and pao2 of 280 mmhg ( on fio2 of 100% ) . her labs were significant for leukocytosis with white cell count of 20,000/mm and an acutely elevated creatinine of 2.2 mg / dl ( baseline creatinine was 0.9 mg / dl at the time of discharge ) with metabolic acidosis with bicarbonate of 18 mmol / l secondary to her renal failure . on further inquiry , there was no exposure to any narcotics or muscle relaxants that might have contributed to her respiratory depression . she was in a supervised unit prior to the presentation , which deterred the possibility of any toxic exposure to the patient . two sets of blood cultures were negative while the wound culture revealed the same biotypes of mdr p. aeruginosa . neurological workup was unrevealing and ventilation / perfusion scan ( v / q scan ) for pulmonary embolism was low probability . colistin was stopped as it was thought to be the cause of renal failure and respiratory failure and the patient was started on imipenem . her respiratory and neurological status remained stable during hospitalization and tolerated imipenem and vancomycin for her osteomyelitis and chronic decubitus ulcer infection . our patient developed acute respiratory failure requiring intubation and mechanical ventilation 6 days after initiation of colistin . respiratory muscle paralysis , as depicted , is one of the manifestations of the neurotoxic effect of colistin . we applied the naranjo adverse drug reaction probability scale to our case , which indicated a probable relationship . the case is limited with the unavailability of arterial blood gas prior to the event as she was emergently intubated on presentation . also , since colistin is reserved for severely ill patients with multiple co - morbidities , it may be difficult to establish direct causal relationship for acute respiratory failure and colistin . colistin was most likely to be the culprit of her respiratory failure from the timing of apnea as well as rapid recovery after stopping colistin . acute renal failure leading to presumed high concentration of serum colistin may be another contributory factor for her respiratory failure . she had a chronic deep vein thrombus which is unlikely to cause acute respiratory failure since low probability for pulmonary embolism by v / q scan and she recovered within 24 hours without any intervention . reported cases of respiratory paralysis associated with polymyxin / colistin use since 1960 to present colistin is also called polymyxin e and is a part of polymyxin family which is a group of polypeptide antibiotics . it exerts its bactericidal effect by displacing the divalent cations magnesium and calcium , which stabilize anionic lipopolysaccharide molecules in the outer membrane of gram - negative bacteria . however , they were gradually abandoned in most parts of the world because of nephrotoxicity and neurotoxicity . the emergence of mdr gram negative bacteria led to the revival of polymyxins in more recent era as a valuable therapeutic option . in the last decade , intravenous polymyxins , particularly in the form of cms , have been used to treat serious p. aeruginosa and a. baumannii infections of various types , including pneumonia , bacteremia , and urinary tract infections . the major manifestations of colistin induced neurotoxicity include dizziness , weakness , facial and peripheral paresthesias , vertigo , visual disturbances , confusion , ataxia , and neuromuscular blockade . koch - weser et al . , reported the incidence of the neurotoxic manifestations to be about 7% , paresthesias being the most common . the proposed mechanism is a non - competitive myoneuronal presynaptic blockade of acetylcholine release , in contrast to the competitive blockade by most other antibiotics like neomycin , kanamycin , and streptomycin . a total of 32 cases of colistin / polymyxin - induced respiratory failure were found in the literature . recent studies have depicted the toxicities associated with colistin use to be less frequent than previously described . the most important risk factor known to be associated with respiratory failure with polymyxin use is the renal disease , which was present in 24 out of 29 patients reported . patients with preexisting renal insufficiency had a greater likelihood of developing nephrotoxicity during colistin therapy , compared to patients with normal baseline renal function . concomitant drug therapies also play a major role in potentiating the effect of neuromuscular blockade , which was noted in 11 out of 29 patients . this includes use of other neurotoxic drugs ( anesthetics , aminoglycosides , and paralytics ) , corticosteroids , narcotics and/or muscle relaxants . most of the cases had other neuromuscular symptoms like circumoral tingling , paresthesias , and restlessness prior to the development of respiratory failure . the duration of apnea lasted from few hours up to several days , maximum noted to be 11 days and 20 out of 29 patients recovered , indicating reversibility of the blockade . the number of doses prior to the respiratory failure seems to be variable and range from a single dose to 45 doses [ table 1 ] . the management of patient with respiratory failure induced by colistin involves discontinuation of the drug and respiratory support . intermittent monitoring of unassisted tidal volumes and forced vital capacity using a bedside spirometer will help determine recovery . monitoring arterial blood gas more importantly , one should be alert for the possibility of respiratory paralysis in any patients receiving this antibiotic and particularly in those patients with renal abnormality and with concomitant neurotoxic drug use . careful observation , regular neurological monitoring , and early appreciation of the symptoms of neuromuscular toxicity especially of dyspnea and restlessness may prevent respiratory arrest . neostigmine is not indicated in polymyxin or colistin - induced neurotoxicity and may be contraindicated as seen in earlier experiments that the blocking action of polymyxin b was shown to be neostigmine resistant . animal studies have noted the ability of polymyxin b to discharge histamine from tissue mast cells , which lead to deposition of chelated calcium along the nerve sheaths , leading to toxicity . higginbotham also reported use of heparin prevents death from respiratory arrest in mice receiving colistin . the use of antihistamines and heparin in polymyxin induced respiratory failure has not been studied in human subjects . as the use of colistin increased in recent years for treatment of life - threatening mdr infections , there are more reports of associated toxicities . clinicians should be aware of colistin - related adverse reactions , especially nephrotoxicity and neurotoxicity . since the formulation of the drug itself has changed , it has necessitated new data with the new formulation . regular monitoring of renal function as well as development of a tool to monitor neurological toxicity is essential to prevent and manage the toxicities associated with colistin use .