The patient is a 67-year-old male from India with a PMH of Ethanol abuse and type 2 diabetes mellitus. He was hospitalized recently in India for 10 days for Ethanol intoxication. The patient returned to America, suffered a mechanical fall, and was hospitalized for altered mental status secondary to Ethanol intoxication. He completed a course of a long-acting benzodiazepine to prevent alcohol withdrawal and took empiric Rocephin for dysuria. The patient was discharged to a rehabilitation center and was soon readmitted to MICU for septic shock, for which he was given vasopressors. Blood and urine cultures grew a highly multidrug resistant E. coli, only sensitive to Tigecycline and Polymixin B. The patient rapidly responded to IV Polymixin B by day 3 of treatment. On day 4, the patient developed acute kidney injury and respiratory distress requiring intubation. Chemistries revealed hypomagnesemia that remained unrepleted for two days. Polymixin B was stopped and the patient recovered full respiratory capacity by the following morning and successfully sustained extubation. His treatment of urosepsis continued with a less optimal antibiotic, tigecycline, for two weeks. The patient was followed by Infectious Disease in the following month and required a second outpatient course of Macrobid followed by maintenance with a urinary antiseptic agent. Renal function continued to improve slowly.
Systemic treatment with Polymixin B is generally avoided nowadays, largely replaced by newer antibiotics with less dangerous side effect profiles. In this case, Polymixin B was the drug of choice to treat this highly multidrug resistant E.coli bacteremia from a urinary source. Nephrotoxic and neurotoxic profiles of Polymyxin are well known, and both adverse reactions became evident in this patient very early into treatment. Polymixin B may cause neuromuscular blockade and respiratory arrest via inhibition of the presynaptic acetylcholine receptors or from a prolonged depolarization phase secondary to hypocalcemia. Accumulation of polymyxins in renal proximal tubule cells, appears to result in ATN and renal dysfunction.
As Polymyxin use is on the rise due to the emergence of multidrug resistant gram-negative infections, strategies to limit or avoid toxicity are gaining interest. For instance, potentiating factors increasing this patient’s risk of developing an adverse reaction, such as hypomagnesemia or the use of long-acting benzodiazepines, may have been addressed beforehand. Another point to consider is that once Polymyxin B was stopped, the patient regained full respiratory function and renal function, albeit slowly, thus attributing to its reversibility.
Polymyxin first came into use over 50 years ago. We are starting to use Polymyxin more frequently due to a rise in carbapenem resistance among gram-negative bacteria. Knowledge of the toxicity profile as well as employing methods to limit adverse events are becoming important. These include minimizing concomitant use of other nephrotoxic agents, avoiding sedatives, monitoring electrolytes, employing critical care, and proper drug dosing and monitoring. Moreover, the apparent reversibility of Polymyxin’s toxicity profile should help guide clinicians in assessing the risk to benefit ratio of continuing to use this drug versus stopping treatment and using strategies to prevent toxic events.