Micafungin therapy in a critically ill, morbidly obese patient

At the time of this episode the patient was on 50 mg of tigecy-cline twice daily iv, and had by that point received 53 days of tigecycline, indicating development of resistance during prolonged tigecycline therapy. The patient was then commenced on colistin [4.5 million units (MU) twice daily iv]. After 10 days of this treatment, the dose was reduced to 3 MU twice daily in the light of rising serum creatinine and elevated colistin levels (trough 8.5 mg/L, peak 10.4 mg/L). On day 13 of colistin treatment, admission to the intensive care unit (ICU) was required for supportive treatment of sepsis. Meropenem and teicoplanin were added empirically to cover the previously isolated P. aeruginosa and MRSA. On day 15 of colistin therapy the patient developed generalized seizures. CT brain scan and CSF were normal. Colistin therapy was discontinued and the seizures stopped shortly afterwards, suggesting colistin-associated neurotoxicity, a recognized side effect. 4 The patient returned to a single room within a general ward after 10 days on the ICU. Subsequent blood cultures were negative. Six months after initial presentation, the patient remains clinically stable. Despite prolonged admission, contact isolation prevented onward transmission of the NDM-positive bacteria within the hospital. This is the first carbapenemase-producing E. coli confirmed to be resistant to tigecycline by the national reference laboratory. An 8-fold reduction in the MIC of tigecycline for the resistant isolate when tested in the presence of the efflux inhibitor phenyl-arginine-b-naphthylamide (PAbN; at 40 mg/L) was observed (compared with only a 2-fold reduction for the susceptible isolate), which suggests up-regulated efflux as the resistance mechanism. Future studies will ascertain the specific pump(s) involved. The isolates remained susceptible to colistin, as do most with NDM enzymes. 5,6 This case suggests that invasive infection with NDM producers can be successfully treated with colistin, albeit with the risk of significant toxicity, and further demonstrates the emerging threat of the NDM-type metallo-b-lactamases. We received the patient's verbal and written consent for their case to be published in a scientific journal for the purposes of medical education and research. N. W. has received research grants and conference support from most major pharmaceutical companies; none represents a conflict of interest with the content of this article. D. M. L. has received grants, speaking invitations and conference invitations from most major pharmaceutical companies and holds shares in GSK, Pfizer, AstraZeneca, Merck, Dechra and Eco Animal Health within diversified portfolios. …