AMR 1: Management of Antimicrobial resistant gram negatives. A Focus on Extended-Spectrum β-lactamase Producing Enterobacterales, Carbapenem-Resistant Enterobacterales, and Pseudomonas aeruginosa with Difficult-to-Treat Resistance
Scenario: You are seeing a 63 yo with CKD and admitted with septic shock. The patient is admitted to the ICU and started on piperacillin-tazobactam and vancomycin. Blood and urine cultures return with ESBL Klebsiella pneumoniae (R-ceftriaxone at MIC >2). It is suspected the cause of the septic shock is pyelonephritis. Within 12 hours the pressors are weened, but the patient continues to have fevers. Do you continue piperacillin-tazobactam or do you change to a carbapenem?
This is not an uncommon scenario. I have encountered many patients that are better(-ish) on an antibiotic that either the organism is resistant to or has a resistance gene that makes the antibiotic less then ideal. Until recently it was difficult to find data to help with management decisions and guide therapy in these situations. Faced with the question of pressing on since there is improvement (and risk worsening sepsis) or change to a carbapenem (and face potential expansion of resistance) is there any guidance or data?
Now there is both guidance and data.
The new IDSA Guidance paper, Infectious Diseases Society of America Antimicrobial Resistant Treatment Guidance: Gram-Negative Bacterial Infections.
The recommendations in this paper are not earth shattering, but they do provide a nice guide for what to do in these vexing situations. The guidance reviews management of AMR in gram negatives, particularly ESBL-Enterobacteriaceae (E. coli, K. pneumoniae, K. oxytoca and P. mirabilis), Carbapenem resistant Enterobacteriaceae and Difficult to Treat (DTR) P aeruginosa. For each organism class there are multiple questions the group attempted to answer and provide some excellent guidance. I have summarized these recommendations in the tables below with some added information.
Empiric therapy: Consider 1) Previous organisms and associated susceptibility data for the last 6 months and 2) Antibiotic exposure in the last 30 days (e.g. if received piperacillin-tazobactam recently consider another class such as a carbapenem)
Duration of therapy: Prolonged treatment courses are not necessary. If the initial antibiotic is found to be inactive, this may change the duration of therapy. As an example, the patient receives 3 days of ceftriaxone, but the E coli is resistant. Days of therapy would start from when an effective therapy was started. Continue reading
