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January 14, 2026Open Forum Infectious Diseases0 citationsOpen Access

P-750. Doxycycline is Inferior to Cephalexin and Sulfamethoxazole/Trimethoprim (SMX/TMP) for the Treatment of Culture Negative Acute Bacterial Skin and Skin Structure Infections (ABSSSIs)

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JJJeffrey W. JansenMLMichael LorenzRMRyan P Moenster

Key Points

  • To compare clinical failure rates of doxycycline, cephalexin, and SMX/TMP in treating culture negative ABSSSI.
  • Retrospective cohort analysis of patients treated for ABSSSI at VA St Louis Healthcare System
  • Included patients aged 18-89 treated with doxycycline, cephalexin, or SMX/TMP
  • Primary outcome was clinical failure defined as specific adverse events within 28 days.
  • Data analyzed with adjustments for various clinically relevant factors.
  • 536 patients included in the analysis.
  • 31.3% clinical failure in doxycycline group versus 16.8% in cephalexin and 18.5% in SMX/TMP.
  • Statistical significance observed between doxycycline and cephalexin (p=0.024) and SMX/TMP (p=0.047).
  • No significant difference in failure rates between cephalexin and SMX/TMP (p=0.628).

Abstract

Abstract Background The 2014 IDSA guidelines recommend empiric treatment for ABSSSI based on categorization of purulent or non-purulent as this provides insight to the causative pathogen. However, in clinical practice, methicillin-resistant Staphylococcus aureus (MRSA) therapy is commonly prescribed in non-purulent infections or infections where serous drainage is mistaken for purulence. Doxycycline is often prescribed for ABSSSI despite limited and antiquated data for its use as a monotherapy option. The current analysis aims to compare the clinical failure rates in patients treated for culture negative ABSSSI with either doxycycline, cephalexin, or SMX/TMP.Table 1:Baseline CharacteristicsTable 2:Clinical Failure vs Antibiotic ReceivedAdjusted p-value using the Bonferroni Correction Methods A retrospective cohort was completed from patients at the VA St Louis Healthcare System aged 18 years through 89 years of age treated for an ABSSSI from either a VA clinic, the emergency room (ER), or inpatient with doxycycline, cephalexin, or TMP/SMX therapy between 10/01/2015 and 12/31/2022. The primary outcome was a composite of clinical failure defined as meeting any of the following within 28 days of antibiotic end date: (1) representation for further evaluation of infection at the same anatomical site; (2) extension or change in antimicrobial agent; and (3) unplanned surgical procedure for treatment of index infection. Key exclusion criteria were patients who received 72 hours intravenous antimicrobial therapy, combination therapy, positive cultures that influenced antibiotic decision, and deep-seated infections.Table 3:Unadjusted Oral Medication vs Clinical FailureTable 4:Adjusted* Oral Medication vs Clinical Failure*Model controlled for age, creatinine clearance, total antibiotic duration, white blood cell count, history of acute bacterial skin and skin structure infection (ABSSSI), history of coronary artery disease, history of cirrhosis, surgical intervention completed at presentation, ABSSSI type, ABSSSI classification, ABSSSI anatomic location, and location managed. Results Overall, 536 patients were included with baseline characteristics are provided in table 1. Thirty patients (31.3%) in the doxycycline group experienced clinical failure, which was statistically significant when compared to cephalexin (43, 16.8%; p = 0.024) and SMX/TMP (34, 18.5%; p = 0.047). Failure rates between SMX/TMP and cephalexin were not significantly different (p = 0.628) (Table 2). Doxycycline therapy was associated with increased clinical failure rates in the regression analysis (Tables 3 and 4). Conclusion Doxycycline is inferior to therapy with cephalexin or SMX/TMP for culture negative ABSSSI regardless of infection classification, location, or type. Disclosures All Authors: No reported disclosures

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Cite This Study

Jansen et al. (2026) studied this question.

synapsesocial.com/papers/6966f2e313bf7a6f02c001dbhttps://doi.org/10.1093/ofid/ofaf695.961
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