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Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam.
BMC Infect Dis. 2017 05 02; 17(1):316.BI

Abstract

BACKGROUND

Diabetes mellitus and hyperglycemia are associated with increased susceptibility to bacterial infections and poor treatment outcomes. This post hoc evaluation of the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) aimed to evaluate baseline characteristics, efficacy, and safety in patients with and without diabetes treated with ceftolozane/tazobactam and comparators. Ceftolozane/tazobactam is an antibacterial with potent activity against Gram-negative pathogens and is approved for the treatment of cIAI (with metronidazole) and cUTI (including pyelonephritis).

METHODS

Patients from the phase 3 ASPECT studies with (n = 245) and without (n = 1802) diabetes were compared to evaluate the baseline characteristics, efficacy, and safety of ceftolozane/tazobactam and active comparators.

RESULTS

Significantly more patients with than without diabetes were 65 years of age or older; patients with diabetes were also more likely to weigh ≥75 kg at baseline (57.1% vs 44.5%), to have renal impairment (48.5% vs 30.2%), or to have APACHE II scores ≥10 (33.8% vs 17.0%). More patients with diabetes had comorbidities and an increased incidence of complicating factors in both cIAI and cUTI. Clinical cIAI and composite cure cUTI rates across study treatments were lower in patients with than without diabetes (cIAI, 75.4% vs 86.1%, P = 0.0196; cUTI, 62.4% vs 74.7%, P = 0.1299) but were generally similar between the ceftolozane/tazobactam and active comparator treatment groups. However, significantly higher composite cure rates were reported with ceftolozane/tazobactam than with levofloxacin in patients without diabetes with cUTI (79.5% vs 69.9%; P = 0.0048). Significantly higher rates of adverse events observed in patients with diabetes were likely due to comorbidities because treatment-related adverse events were similar between groups.

CONCLUSIONS

In this post hoc analysis, patients with diabetes in general were older, heavier, and had a greater number of complicating comorbidities. Patients with diabetes had lower cure rates and a significantly higher frequency of adverse events than patients without diabetes, likely because of the higher rates of medical complications in this subgroup. Ceftolozane/tazobactam was shown to be at least as effective as comparators in treating cUTI and cIAI in this population.

TRIAL REGISTRATION

cIAI, NCT01445665 and NCT01445678 (both trials registered prospectively on September 26, 2011); cUTI, NCT01345929 and NCT01345955 (both trials registered prospectively on April 28, 2011).

Authors+Show Affiliations

Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. myra.popejoy@merck.com.Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study

Language

eng

PubMed ID

28464828

Citation

Popejoy, Myra W., et al. "Analysis of Patients With Diabetes and Complicated Intra-abdominal Infection or Complicated Urinary Tract Infection in Phase 3 Trials of Ceftolozane/tazobactam." BMC Infectious Diseases, vol. 17, no. 1, 2017, p. 316.
Popejoy MW, Long J, Huntington JA. Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam. BMC Infect Dis. 2017;17(1):316.
Popejoy, M. W., Long, J., & Huntington, J. A. (2017). Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam. BMC Infectious Diseases, 17(1), 316. https://doi.org/10.1186/s12879-017-2414-9
Popejoy MW, Long J, Huntington JA. Analysis of Patients With Diabetes and Complicated Intra-abdominal Infection or Complicated Urinary Tract Infection in Phase 3 Trials of Ceftolozane/tazobactam. BMC Infect Dis. 2017 05 2;17(1):316. PubMed PMID: 28464828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam. AU - Popejoy,Myra W, AU - Long,Jianmin, AU - Huntington,Jennifer A, Y1 - 2017/05/02/ PY - 2016/12/10/received PY - 2017/04/21/accepted PY - 2017/5/4/entrez PY - 2017/5/4/pubmed PY - 2017/8/26/medline KW - Ceftolozane/tazobactam KW - Complicated intra-abdominal infections KW - Complicated urinary tract infections KW - Diabetes mellitus SP - 316 EP - 316 JF - BMC infectious diseases JO - BMC Infect Dis VL - 17 IS - 1 N2 - BACKGROUND: Diabetes mellitus and hyperglycemia are associated with increased susceptibility to bacterial infections and poor treatment outcomes. This post hoc evaluation of the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) aimed to evaluate baseline characteristics, efficacy, and safety in patients with and without diabetes treated with ceftolozane/tazobactam and comparators. Ceftolozane/tazobactam is an antibacterial with potent activity against Gram-negative pathogens and is approved for the treatment of cIAI (with metronidazole) and cUTI (including pyelonephritis). METHODS: Patients from the phase 3 ASPECT studies with (n = 245) and without (n = 1802) diabetes were compared to evaluate the baseline characteristics, efficacy, and safety of ceftolozane/tazobactam and active comparators. RESULTS: Significantly more patients with than without diabetes were 65 years of age or older; patients with diabetes were also more likely to weigh ≥75 kg at baseline (57.1% vs 44.5%), to have renal impairment (48.5% vs 30.2%), or to have APACHE II scores ≥10 (33.8% vs 17.0%). More patients with diabetes had comorbidities and an increased incidence of complicating factors in both cIAI and cUTI. Clinical cIAI and composite cure cUTI rates across study treatments were lower in patients with than without diabetes (cIAI, 75.4% vs 86.1%, P = 0.0196; cUTI, 62.4% vs 74.7%, P = 0.1299) but were generally similar between the ceftolozane/tazobactam and active comparator treatment groups. However, significantly higher composite cure rates were reported with ceftolozane/tazobactam than with levofloxacin in patients without diabetes with cUTI (79.5% vs 69.9%; P = 0.0048). Significantly higher rates of adverse events observed in patients with diabetes were likely due to comorbidities because treatment-related adverse events were similar between groups. CONCLUSIONS: In this post hoc analysis, patients with diabetes in general were older, heavier, and had a greater number of complicating comorbidities. Patients with diabetes had lower cure rates and a significantly higher frequency of adverse events than patients without diabetes, likely because of the higher rates of medical complications in this subgroup. Ceftolozane/tazobactam was shown to be at least as effective as comparators in treating cUTI and cIAI in this population. TRIAL REGISTRATION: cIAI, NCT01445665 and NCT01445678 (both trials registered prospectively on September 26, 2011); cUTI, NCT01345929 and NCT01345955 (both trials registered prospectively on April 28, 2011). SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/28464828/Analysis_of_patients_with_diabetes_and_complicated_intra_abdominal_infection_or_complicated_urinary_tract_infection_in_phase_3_trials_of_ceftolozane/tazobactam_ L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-017-2414-9 DB - PRIME DP - Unbound Medicine ER -