Hospital Pharmacy - February 2020 - 47

Tullos et al
Table 3. Criteria Met for Lack of Clinical Response.

Repeat admission for the
same UTIa
Positive repeat urine culturesa
Change in antimicrobial
regimen occurred

PTZ
(n = 39)

Carbapenem
(n = 141)

P
value

6 (15.4%)

28 (19.9%)

.65

6 (15.4%)
1 (2.6%)

21 (14.9%)
3 (2.1%)

1
1

Note. PTZ = piperacillin-tazobactam; UTI = urinary tract infection.
a
Within 6 months.

Table 4. MIC Data.
Piperacillin MICa (μg/mL)
≤4
8
16
32

PTZa (n = 38)b
28 (73.7%)
7 (18.4%)
1 (2.6%)
2 (5.3%)

Note. MIC = minimum inhibitory concentration; PTZ = piperacillintazobactam.
a
MIC was determined using Vitek2.
b
MIC for one isolate was not reported.

length of hospital stay (11.1 vs 8.6 days; P = .063) between
PTZ and carbapenem groups, respectively (Figure 3).
Inpatient mortality was also comparable between the two
groups (2.1% vs 0%; P = 1), with the majority of patients surviving at discharge.

Discussion
The results from this study suggest that PTZ could be used
as an alternative to carbapenems for treatment of nonbacteremic UTIs due to ESBL-producing Enterobacteriaceae
when isolates are susceptible based on lab testing. The successful use of PTZ for UTIs may partly be due to its ability
to reach high concentrations in the urine. In a study conducted by Gavin et al., PTZ cured all patients with UTIs
regardless of piperacillin MIC.12 Although 100% cure was
not demonstrated in the PTZ group in our study, the clinical
response seen in our isolates with higher piperacillin MICs
suggest that response of urinary isolates to PTZ may occur
even when MIC is higher. Of note, two isolates in the PTZ
group were reported to have a MIC of 32 μg/mL which at
the time of treatment was reported as sensitive by the microbiology lab, though at the time of this study is now reported
as intermediate. These isolates were included in the evaluation because they were reported to be sensitive at the time of
treatment and reflect a realistic clinical situation where decision-making was based on sensitivity reports. Due to the
perceived advantage of carbapenems and their status as preferred in the treatment of ESBL Enterobacteriaceae UTI,
there was a larger proportion of patients receiving carbapenem therapy in the study time frame.

Our study does have some strengths to note. This study
was conducted on data from multiple hospitals. While in the
same general geographic area, the incorporation of multiple
medical centers allowed us to evaluate data from urban, suburban, and rural patient populations. In addition to the incorporation of multiple centers and therefore a more varied
patient population, we feel that there is opportunity for substantial practical application of the results as they represent
data directly from clinical practice. We chose a composite
endpoint of clinical response to focus on treatment outcomes
rather than microbiologic outcomes. We feel that due to the
complexities of treating patients with ESBL Enterobacteriaceae
UTI, targeting an outcome of clinical response would contribute to the body of evidence regarding the use of PTZ in these
clinical situations.
This study has several limitations that should be considered. First, the retrospective study design made it difficult to
eliminate information and/or selection bias as well as any
unknown confounding factors that may have affected the
evaluation of treatment efficacy. We were also unable to
ascertain the factors that affected physician decisions regarding choice of antimicrobial therapy, which was one of the
factors used in determining clinical response. It is possible
that the patients treated with PTZ requiring a change in antimicrobial therapy represented physician preference toward
carbapenems once the ESBL isolate was realized, and these
changes in therapy may not truly represent treatment failure
(Table 3). Second, determining microbiological clearance
was challenging since repeat urinalysis and urine cultures are
not routinely recommended based on current guidelines.
Third, assumptions regarding treatment efficacy were made
due to the inability for patient follow-up after discharge.
Fourth, the antimicrobial regimen at discharge was not
standardized, and any deescalation to oral therapy that may
have provided benefit is a potential confounder in our
results. Fifth, classification of complicated and uncomplicated UTIs was not made as this differentiation relies on
data that were not collected. Details concerning removal of
catheters were an additional limitation in data collection.
Finally, a true definition of UTI was not established in our
study and was confirmed solely based on urine culture
reports, physician documentation indicating clinical suspicion of UTI and decision to treat. It is likely that some urine
culture reports represent colonization; however, this study
was conducted at sites where antimicrobial stewardship
programs have been implemented and treatment of asymptomatic bacteriuria is strongly discouraged. It was decided
not to determine the presence of asymptomatic bacteriuria
based on chart review alone as this may fail to capture urinary symptoms. Asymptomatic bacteriuria was documented
in two patients, both in the carbapenem group. It was determined that this finding was minimal and did not require
further evaluation. Inappropriate use of antimicrobials for
treatment of asymptomatic bacteriuria is likely a common
practice seen in various institutional settings.

Hospital Pharmacy - February 2020

Table of Contents for the Digital Edition of Hospital Pharmacy - February 2020