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Background &amp; objectives <p>Multidrug-resistant (MDR) <i>Klebsiella pneumoniae</i> poses a critical treatment challenge. Colistin remains a last-resort antibiotic but is limited by nephrotoxicity and resistance. Though clinical data are limited, Doxycycline has demonstrated in vitro synergy with colistin. Colistin–meropenem is frequently used as a comparator regimen, despite mixed evidence on its synergistic activity. This study evaluates the efficacy, microbiological response, and safety of colistin–doxycycline versus colistin–meropenem in MDR Gram-negative infections.</p> Methods <p>A double-blind, randomized controlled trial was conducted at a teaching hospital. Adult patients with culture-confirmed MDR <i>Klebsiella pneumoniae</i> infections were randomized to receive colistin–doxycycline or colistin–meropenem. The primary outcome was clinical cure, defined as resolution of infection signs without therapy escalation and in-hospital mortality. Secondary outcomes included microbiological eradication, acute kidney injury (AKI), and treatment-related adverse events. Patients were followed throughout hospitalization and for 14 days post-treatment.</p> Results <p>A total of 46 patients were enrolled, with 23 patients in each group. Clinical cure rates were significantly higher in the colistin–doxycycline group (87.0% vs. 46.7%, <i>p</i> = 0.012), and mortality was lower (69.6% vs. 86.7%, <i>p</i> = 0.017). Microbiological eradication was also superior (<i>p</i> = 0.016), and nephrotoxicity incidence was numerically lower (19.1% vs. 33.3%, <i>p</i> = 0.092). Faster resolution of inflammation (<i>p</i> &lt; 0.05) and reduced need for mechanical ventilation (60.9% vs. 33.3%, <i>p</i> = 0.028) were observed in the colistin–doxycycline group.</p> Conclusions <p>Colistin–doxycycline showed superior efficacy to colistin–meropenem in MDR <i>Klebsiella pneumoniae</i> infections, with higher cure rates, better bacterial eradication, and a favorable safety trend. These results support its potential as a possible alternative option in managing MDR Gram-negative infections, though confirmation in larger multicenter trials is needed.</p> Graphical abstract <p></p>

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Efficacy and safety of colistin–doxycycline combination therapy in multi-drug resistance Gram-negative infections: a double-blind randomized controlled trial

  • 期刊论文

  • 发表日期：

    2025年11月20日

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  • Shaghayegh Abaft,
  • Zeynab Yassin,
  • Mahdi Ahmadinia,
  • Azadeh Eshraghi,
  • Behnaz Gholizadeh Niari,
  • Sara Minaeian,
  • Maryam Farasatinasab

摘要

Background & objectives

Multidrug-resistant (MDR) Klebsiella pneumoniae poses a critical treatment challenge. Colistin remains a last-resort antibiotic but is limited by nephrotoxicity and resistance. Though clinical data are limited, Doxycycline has demonstrated in vitro synergy with colistin. Colistin–meropenem is frequently used as a comparator regimen, despite mixed evidence on its synergistic activity. This study evaluates the efficacy, microbiological response, and safety of colistin–doxycycline versus colistin–meropenem in MDR Gram-negative infections.

Methods

A double-blind, randomized controlled trial was conducted at a teaching hospital. Adult patients with culture-confirmed MDR Klebsiella pneumoniae infections were randomized to receive colistin–doxycycline or colistin–meropenem. The primary outcome was clinical cure, defined as resolution of infection signs without therapy escalation and in-hospital mortality. Secondary outcomes included microbiological eradication, acute kidney injury (AKI), and treatment-related adverse events. Patients were followed throughout hospitalization and for 14 days post-treatment.

Results

A total of 46 patients were enrolled, with 23 patients in each group. Clinical cure rates were significantly higher in the colistin–doxycycline group (87.0% vs. 46.7%, p = 0.012), and mortality was lower (69.6% vs. 86.7%, p = 0.017). Microbiological eradication was also superior (p = 0.016), and nephrotoxicity incidence was numerically lower (19.1% vs. 33.3%, p = 0.092). Faster resolution of inflammation (p < 0.05) and reduced need for mechanical ventilation (60.9% vs. 33.3%, p = 0.028) were observed in the colistin–doxycycline group.

Conclusions

Colistin–doxycycline showed superior efficacy to colistin–meropenem in MDR Klebsiella pneumoniae infections, with higher cure rates, better bacterial eradication, and a favorable safety trend. These results support its potential as a possible alternative option in managing MDR Gram-negative infections, though confirmation in larger multicenter trials is needed.

Graphical abstract