Evaluation of the efficacy of step-down therapy with oral minocycline for complicated pyelonephritis caused by extended-spectrum β-lactamase-producing enterobacterales: A retrospective cohort study

Background

Extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) infections present significant treatment challenges owing to limited oral antibiotic options. Minocycline is active against ESBL-E; however, its efficacy remains unclear. This study evaluated the efficacy of step-down therapy using oral minocycline for complicated pyelonephritis (cPN) caused by ESBL-producing Escherichia coli.

Methods

This retrospective cohort study, conducted at Tohoku Rosai Hospital (2018–2023), included hospitalized patients with cPN and ESBL-E infection. Seventy-two patients receiving intravenous antibiotics followed by oral therapy were classified into the conventional or minocycline therapy groups. Primary outcomes were recurrence within 30 and 90 days post-treatment, whereas secondary outcomes included resolution of fever within 48 h, hospital stay, and adverse events. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed.

Results

No significant differences were observed in recurrence or fever resolution; however, hospital stay was shorter in the minocycline group than in the conventional group (PSM: p = 0.027; IPTW: p = 0.033, respectively). No adverse effects were noted, although one Clostridioides difficile infection case occurred in the conventional group. ESBL-producing E. coli was detected more frequently in the minocycline therapy group (p = 0.005), and patients with minocycline minimum inhibitory concentration (MIC) ≥4 μg/mL had higher relapse rates (p = 0.006) than those in the conventional group.

Conclusions

Among ESBL-E, particularly in E. coli, step-down therapy using oral minocycline for cPN appears as effective as conventional therapy and may shorten hospital stays. However, as minocycline MICs ≥4 μg/mL may be associated with recurrence, clinicians should verify MIC values before prescribing minocycline.