Piperacillin–tazobactam combo useful for treating ESBL-producing pyelonephritis

The combination of piperacillin plus tazobactam (TZP) performs well in the management of nonbacteraemic pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing organisms, with rates of symptom resolution and 30-day mortality similar to that achieved with carbapenem, as shown in a recent study.

“This study highlights the potential utility of TZP as a carbapenem-sparing agent for the management of ESBL-producing pyelonephritis,” according to the investigators, adding that the combination may “mitigate the risk of emergence of carbapenem-resistant organisms.”

The current propensity-score weighted analysis included 186 patients (median age, 63 years; 68 percent female) with ESBL-producing pyelonephritis treated with either TZP (n=45; median treatment duration, 8 days) or a carbapenem (n=141; median treatment duration, 8 days).

Of the patients, 27 percent were admitted to the intensive care unit, 48 percent were immunocompromised, and 45 percent had underlying urologic abnormalities. Commonly identified organisms in urine cultures were Escherichia coli (56 percent) and Klebsiella pneumoniae (30 percent).

The primary outcome of recurrent cystitis or pyelonephritis with the same ESBL organism within 30 days of treatment initiation occurred in 44 patients (24 percent) overall, and the proportion was similar in the TZP and carbapenem groups (20 percent vs 25 percent; odds ratio [OR], 0.75, 95 percent confidence interval [CI], 0.31–1.81; p=0.52). [Clin Infect Dis 2019;doi:10.1093/cid/ciz1205]

Likewise, there were no significant between-group differences observed in the following secondary outcomes: resolution of symptoms within 7 days (OR, 1.79, 95 percent CI, 0.50–6.46; p=0.37), 30-day mortality (OR, 0.38, 95 percent CI, 0.05–3.06; p=0.36), and incident carbapenem-resistant organism recovered within 60 days (OR, 0.16, 95 percent CI, 0.02–1.29; p=0.09).

“Our findings suggest that TZP therapy may result in similar clinical outcomes as carbapenem therapy for the treatment of hospitalized patients with pyelonephritis caused by ESBL-producing organisms in the absence of bacteraemia,” the investigators said.

Despite the presence of several limitations, the present study may have important implications, since the rising burden of carbapenem-resistant organisms is well-recognized as a global crisis. Previous reports have also identified preceding carbapenem use as a risk factor for the subsequent development of infections with carbapenem-resistant gram-negative organisms. [apps.who.int/iris/bitstream/handle/10665/259462/9789241550178-eng.pdf; Open Forum Infect Dis 2019;6:ofz027; J Antimicrob Chemother 2017;72:1496-1501; Infect Drug Resist 2019;12:461-468]

“Although not statistically significant, our study also suggests a trend towards an increased risk of harbouring carbapenem-resistant organisms with previous carbapenem exposure. This is particularly worrisome as a number of studies have indicated that patients who previously received antibiotics to treat bacteria isolated from the urine, regardless of whether antibiotics were indicated, are at an increased risk of a subsequent urinary tract infection (UTI)—in the range of 24–44 percent in the next 6–12 months,” the investigators noted. [Clin Infect Dis 2012;55:771-777; Infect Dis Clin North Am 2014;28:1-13]

“As almost half of our cohort had underlying urologic abnormalities and are likely to have future UTIs, this finding underscores the importance of judicious antibiotic prescribing for the treatment of UTIs,” they added, acknowledging that the data should be validated in adequately powered and appropriately designed randomized control trials.