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Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial.
J Antimicrob Chemother. 2016 07; 71(7):2014-21.JA

Abstract

OBJECTIVES

Empirical fluoroquinolone therapy is widely used in treating complicated urinary tract infections (cUTIs), even in areas of high fluoroquinolone resistance. While it is believed that high antibiotic concentrations in urine might be sufficient to overcome and effectively treat infections caused by resistant bacteria, clinical trial data validating this assumption are limited. This post hoc analysis evaluated the efficacy of ceftolozane/tazobactam versus levofloxacin in the subgroup of patients with cUTIs caused by levofloxacin-resistant pathogens in a randomized, controlled trial (NCT01345929/NCT01345955).

METHODS

Hospitalized adults with cUTI/pyelonephritis were randomized to 7 days of 1.5 g of ceftolozane/tazobactam every 8 h or 750 mg of levofloxacin once daily, before availability of culture and susceptibility data. A composite of microbiological eradication and clinical cure 5 to 9 days post-therapy was assessed in the microbiological modified ITT (mMITT; n = 800) and microbiologically evaluable (ME; n = 694) populations.

RESULTS

In the mMITT population, there were 212 patients (26.5%) with at least one baseline uropathogen that was resistant to levofloxacin. The majority of uropathogens in this subgroup were Enterobacteriaceae (n = 186) that were susceptible to ceftolozane/tazobactam [MIC ≤2 mg/L, 88.7% (165/186)]. Among patients with levofloxacin-resistant pathogens, ceftolozane/tazobactam demonstrated significantly higher composite cure rates than levofloxacin in both the mMITT [60.0% (60/100) versus 39.3% (44/112); 95% CI for the treatment difference, 7.2%-33.2%] and ME [64.0% (57/89) versus 43.4% (43/99); 95% CI for the treatment difference, 6.3%-33.7%] populations, respectively.

CONCLUSIONS

High urinary levels of levofloxacin did not reliably cure cUTIs. Seven day treatment with ceftolozane/tazobactam was more effective than high-dose levofloxacin treatment in patients with cUTI caused by levofloxacin-resistant bacteria, and it may be an alternative treatment in settings of increased fluoroquinolone resistance.

Authors+Show Affiliations

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA jennifer.huntington@merck.com.University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA.Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.R.M. Alden Research Laboratory, 2021 Santa Monica Boulevard, Suite 740-E, Los Angeles, CA 90404, USA UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

26994090

Citation

Huntington, Jennifer A., et al. "Efficacy of Ceftolozane/tazobactam Versus Levofloxacin in the Treatment of Complicated Urinary Tract Infections (cUTIs) Caused By Levofloxacin-resistant Pathogens: Results From the ASPECT-cUTI Trial." The Journal of Antimicrobial Chemotherapy, vol. 71, no. 7, 2016, pp. 2014-21.
Huntington JA, Sakoulas G, Umeh O, et al. Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial. J Antimicrob Chemother. 2016;71(7):2014-21.
Huntington, J. A., Sakoulas, G., Umeh, O., Cloutier, D. J., Steenbergen, J. N., Bliss, C., & Goldstein, E. J. (2016). Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial. The Journal of Antimicrobial Chemotherapy, 71(7), 2014-21. https://doi.org/10.1093/jac/dkw053
Huntington JA, et al. Efficacy of Ceftolozane/tazobactam Versus Levofloxacin in the Treatment of Complicated Urinary Tract Infections (cUTIs) Caused By Levofloxacin-resistant Pathogens: Results From the ASPECT-cUTI Trial. J Antimicrob Chemother. 2016;71(7):2014-21. PubMed PMID: 26994090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial. AU - Huntington,Jennifer A, AU - Sakoulas,George, AU - Umeh,Obiamiwe, AU - Cloutier,Daniel J, AU - Steenbergen,Judith N, AU - Bliss,Caleb, AU - Goldstein,Ellie J C, Y1 - 2016/03/18/ PY - 2015/08/26/received PY - 2016/02/10/accepted PY - 2016/3/20/entrez PY - 2016/3/20/pubmed PY - 2017/8/23/medline SP - 2014 EP - 21 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 71 IS - 7 N2 - OBJECTIVES: Empirical fluoroquinolone therapy is widely used in treating complicated urinary tract infections (cUTIs), even in areas of high fluoroquinolone resistance. While it is believed that high antibiotic concentrations in urine might be sufficient to overcome and effectively treat infections caused by resistant bacteria, clinical trial data validating this assumption are limited. This post hoc analysis evaluated the efficacy of ceftolozane/tazobactam versus levofloxacin in the subgroup of patients with cUTIs caused by levofloxacin-resistant pathogens in a randomized, controlled trial (NCT01345929/NCT01345955). METHODS: Hospitalized adults with cUTI/pyelonephritis were randomized to 7 days of 1.5 g of ceftolozane/tazobactam every 8 h or 750 mg of levofloxacin once daily, before availability of culture and susceptibility data. A composite of microbiological eradication and clinical cure 5 to 9 days post-therapy was assessed in the microbiological modified ITT (mMITT; n = 800) and microbiologically evaluable (ME; n = 694) populations. RESULTS: In the mMITT population, there were 212 patients (26.5%) with at least one baseline uropathogen that was resistant to levofloxacin. The majority of uropathogens in this subgroup were Enterobacteriaceae (n = 186) that were susceptible to ceftolozane/tazobactam [MIC ≤2 mg/L, 88.7% (165/186)]. Among patients with levofloxacin-resistant pathogens, ceftolozane/tazobactam demonstrated significantly higher composite cure rates than levofloxacin in both the mMITT [60.0% (60/100) versus 39.3% (44/112); 95% CI for the treatment difference, 7.2%-33.2%] and ME [64.0% (57/89) versus 43.4% (43/99); 95% CI for the treatment difference, 6.3%-33.7%] populations, respectively. CONCLUSIONS: High urinary levels of levofloxacin did not reliably cure cUTIs. Seven day treatment with ceftolozane/tazobactam was more effective than high-dose levofloxacin treatment in patients with cUTI caused by levofloxacin-resistant bacteria, and it may be an alternative treatment in settings of increased fluoroquinolone resistance. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/26994090/Efficacy_of_ceftolozane/tazobactam_versus_levofloxacin_in_the_treatment_of_complicated_urinary_tract_infections__cUTIs__caused_by_levofloxacin_resistant_pathogens:_results_from_the_ASPECT_cUTI_trial_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkw053 DB - PRIME DP - Unbound Medicine ER -