A recent study presented by Taylor Hein, MLS, at the 2025 MAD-ID Meeting explored the in vitro activity of ceftolozane/tazobactam (C/T) against ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis from clinical samples. Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae continue to pose serious challenges in clinical settings due to resistance to extended-spectrum cephalosporins. While carbapenems remain a mainstay of treatment, growing antimicrobial resistance has fueled interest in carbapenem-sparing agents. The research was led by Jose Alexander, MD, ABMM, ABAIM, FCCM, CIC, ASCP, BCMAS, medical director for the microbiology laboratory at Adventhealth in Orlando.
In our interview, Alexander said, “The whole idea started when the IDSA, last year, published guidance for antimicrobial-resistant organisms indicating that ceftolozane/tazobactam can be an option for ESBL in certain infections. We know some of our clinicians are using ceftolozane/tazobactam for ESBL, even though we don’t routinely test for this type of organism. The goal was to establish how this agent performs against ESBL organisms across our institution.”
The study analyzed 125 ESBL-producing isolates collected primarily from urinary sources across AdventHealth Central Florida Division campuses. The breakdown included E coli (n=95), K pneumoniae (n=25), and P mirabilis (n=5). Identification was performed using biochemical methods or MALDI-TOF (VitekMS), and ESBL status was confirmed using VITEK2 AST-GN81 cards. C/T susceptibility was tested via MIC gradient strips, with results interpreted according to 2023 CLSI M100 breakpoints.
Among the findings: 98% of E coli isolates were susceptible to ceftolozane/tazobactam, with an MIC90 of 1 mcg/mL. “We tested 95 ESBL-producing E coli isolates, and 98% of them were susceptible,” said Alexander. “That means if a patient has an ESBL E coli infection and the clinician chooses ceftolozane/tazobactam, there’s only a 2% chance the organism might be resistant. Using this drug upfront, while awaiting lab confirmation, could be justified—especially for inpatients, but potentially in both settings.”
In contrast, the performance of C/T against K pneumoniae was notably lower. Only 76% of isolates were susceptible, with 6 of 25 showing resistance and an MIC90 of 8 mcg/mL. “Klebsiella pneumoniae was more surprising. We tested 25 isolates—it’s the second most prevalent ESBL at our institution—and only 76% were susceptible. That leaves 24% resistant,” Alexander explained. “So, for clinicians considering this drug for K pneumoniae ESBLs, we strongly recommend confirming susceptibility with lab testing before switching to ceftolozane/tazobactam.”
All five P mirabilis isolates were fully susceptible, although no MIC90 was calculated due to the small sample size. “That’s too small a sample to draw conclusions, but all were susceptible,” Alexander said. These results underscore the need for species-specific susceptibility testing before selecting ceftolozane/tazobactam as targeted therapy. While E coli and P mirabilis results support its potential use as an early empiric agent, caution is advised with K pneumoniae.
“Probably the most surprising was Klebsiella pneumoniae, with about 24% resistance. We don’t have local historical data to compare, but this could be something intrinsic to this organism. It may naturally tend to be more resistant, and some strains could also carry AmpC—another resistance mechanism similar to ESBL,” said Alexander.
He emphasized that in-vitro findings should eventually be correlated with clinical outcomes. “Another key point is that in vitro data doesn’t always correlate with clinical outcomes. So it will be critical to match this lab data with actual outcomes in patients treated with ceftolozane/tazobactam for ESBL infections. That’s part of our contribution—sharing in vitro results while hoping to expand this data set to include clinical outcomes as well.”
