What’s the mechanism of resistance (gene, and effect) seen in Escherichia coli (E. coli) that induces resistance to piperacillin-tazobactam but retains susceptibility to cephalosporins?
Benjamin Newell, PharmD, PGY1 Resident; Nathan Wirick, PharmD, BCPS, BCIDP; Sandra Axtell, PharmD, BCPS. Cleveland Clinic Hillcrest Hospital
There are various resistance mechanisms that have been described forE. coli. However, in the case of piperacillin-tazobactam resistance and cephalosporin susceptibility it involves an amino acid substation in the blaTEM-1 and blaSHV-1gene markers.1These gene variations are capable of hydrolyzing penicillins and first generation cephalosporins, without effecting oxyimino cephalosporins. Ceftazidime, cefuroxime,ceftriaxone, and cefepime are all oxyimino cephalosporins.1,2
Investigators explored E. coli isolates with these gene characteristics and of the 32 isolates, 28 (88%) harbored blaTEM-1 and blaSHV-1 and none contained an extended-spectrum beta lactamase (ESBL)-AmpC beta-lactamase gene which would elicit greater cephalosporin resistance.2 Common risk factors associated with TEM-1 and SHV-1 isolates are recenthospitalization, hematologic malignancy, and gastrointestinal tract infection. The ability to recognize these high-risk patients can potentially aid in de-escalation of carbapenems and utilization of cephalosporins instead to assist in reserving carbapenems for ESBL-AmpC producing enterobacteriaceae.2 Testing for these variations would be ideal but without commercial laboratory tests for these genes, providers will need to utilize susceptibilities to identify possible mutated isolates.
A case report describing this particular resistance mechanism involved a patient who presented with sepsis and was initiated on piperacillin-tazobactam, however did not exhibit clinical improvement after four days of therapy. Once susceptibility data was available, the patient was transitioned to ceftriaxone, andthere was significant clinical improvement.3Investigators examined a similar scenario that de-escalation of therapy to ceftriaxone is safe and effective once the blood stream isolate is identified as E. coli in the absence of ESBL.4
In conclusion, the incidence of TEM-1 or SHV-1 genes is low, only 3% ratereportedat one health-system over 2 years.3 Initiating a third or fourth generation cephalosporin may be beneficial over piperacillin-tazobactam, if these isolates are more frequent unless anaerobic or enteroocccal coverage is necessary. There may also be consideration of converting patients to cefepime or ceftriaxone if the patient is slow to respond to piperacillin-tazobactam, since it will take approximately two days to have susceptibilities back from the culture draw and there is no commercial product to detect these genes on a susceptibility report. This way patients are treated appropriately and de-escalation can occur at a timely rate.
Shaikh S, Fatima J, Shakil S, Rizvi, S, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: Types epidemiology and treatment. Saudi J Biol Sci. 2015 Jan;22(1):90-101.
Baker TM, Rogers W, Chavada KD, Westblade LF, Jenkins SG, Nicolau DP. Epidemiology of Bloodstream Infections Caused by Escherichia coli and Klebsiella pneumonia that are piperacillin-tazobactam-nonsusceptible but ceftriaxone-susceptible. Open forum Infect Dis. 2018 Nov 19;5(12):300-7.
Carlisle L, Justo JA, Al-Hasan MN. Bloodstream infection due to piperacillin/tazobactam non-susceptible, cephalosporin-susceptible Escherichia coli: A missed opportunity for de-escalation of therapy. Antibiotics 2018;(7)4:104.
Bookstaver PB, Nimmich EB, Smith TJ, Justo JA, Krohn J, Hammer KL, Troficanto C. Cumulative effect of an antimicrobial stewardship and rapid diagnostic testing bundle on early streamlining of antimicrobial therapy in gram negative bloodstream infections. Antimicrob Agents Chemother.2017 Aug 24;61(9):189-17.