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<p>The proliferation of multidrug-resistant, metallo-beta-lactamase-producing <i>Klebsiella pneumoniae</i> (MBL-producing <i>K. pneumoniae</i>) poses a major threat to public health resulting in increasing treatment costs, prolonged hospitalization, and mortality rate. Treating such bacteria presents substantial hurdles for clinicians. The combination of Aztreonam (ATM) and ceftazidime/avibactam (CAZ/AVI) is likely the most successful approach. The study evaluated the in vitro activity of CAZ/AVI in combination with ATM against MBL-producing&#xa0;<i>K. pneumoniae</i>&#xa0;clinical isolates collected from Suez Canal University Hospital patients. Carbapenem-resistant <i>K. pneumoniae</i> were isolated and identified from different specimens. The presence of metallo-β-lactamases was detected phenotypically by modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) testing, and genotypically for the three metallo-β-lactamase genes: <i>bla</i>NDM, <i>bla</i>IMP, and <i>bla</i>VIM by conventional PCR method. The synergistic effect of CAZ/AVI with ATM against MBL-producing&#xa0;<i>K. pneumoniae</i>&#xa0;was detected by ceftazidime-avibactam combination disks and E-test for antimicrobial susceptibility testing. Out of the 65 K. pneumoniae isolates recovered, 60% (39/65) were carbapenem-resistant (CRKP). According to the mCIM and eCIM tests, 89.7% (35/39) of CRKP isolates were carbapenemase-positive, and 68.6% (24/35) were metallo-β-lactamase (MBL)-positive. By using the conventional PCR, at least one of the MBL genes was present in each metallo-bata-lactamase-producing isolate: 8.3% carried the <i>bla</i>VIM gene, 66.7% the <i>bla</i>NDM, and 91.7% the <i>bla</i>IMP gene. After doing the disk combination method for ceftazidime-avibactam plus Aztreonam, 62.5% of the isolates shifted from resistance to sensitivity. Also, ceftazidime/avibactam plus Aztreonam resistance was reduced markedly among CRKP using the E-test. The addition of Aztreonam to ceftazidime/avibactam is an effective therapeutic option against MBL-producing&#xa0;<i>K. pneumoniae</i>.</p><p><b>Clinical Trials Registry</b>: Pan African Clinical Trials Registry. Trial No.: PACTR202410744344899. Trial URL: <a href="https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=32000">https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=32000</a></p>

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Synergistic combination of ceftazidime and avibactam with Aztreonam against MDR Klebsiella pneumoniae in ICU patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月11日

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  • Sally Khattab,
  • Aya Mohamed Askar,
  • Hidi A. A. Abdellatif,
  • Amira A. A. Othman,
  • Amal H. Rayan,
  • Hasnaa Azab

摘要

The proliferation of multidrug-resistant, metallo-beta-lactamase-producing Klebsiella pneumoniae (MBL-producing K. pneumoniae) poses a major threat to public health resulting in increasing treatment costs, prolonged hospitalization, and mortality rate. Treating such bacteria presents substantial hurdles for clinicians. The combination of Aztreonam (ATM) and ceftazidime/avibactam (CAZ/AVI) is likely the most successful approach. The study evaluated the in vitro activity of CAZ/AVI in combination with ATM against MBL-producing K. pneumoniae clinical isolates collected from Suez Canal University Hospital patients. Carbapenem-resistant K. pneumoniae were isolated and identified from different specimens. The presence of metallo-β-lactamases was detected phenotypically by modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) testing, and genotypically for the three metallo-β-lactamase genes: blaNDM, blaIMP, and blaVIM by conventional PCR method. The synergistic effect of CAZ/AVI with ATM against MBL-producing K. pneumoniae was detected by ceftazidime-avibactam combination disks and E-test for antimicrobial susceptibility testing. Out of the 65 K. pneumoniae isolates recovered, 60% (39/65) were carbapenem-resistant (CRKP). According to the mCIM and eCIM tests, 89.7% (35/39) of CRKP isolates were carbapenemase-positive, and 68.6% (24/35) were metallo-β-lactamase (MBL)-positive. By using the conventional PCR, at least one of the MBL genes was present in each metallo-bata-lactamase-producing isolate: 8.3% carried the blaVIM gene, 66.7% the blaNDM, and 91.7% the blaIMP gene. After doing the disk combination method for ceftazidime-avibactam plus Aztreonam, 62.5% of the isolates shifted from resistance to sensitivity. Also, ceftazidime/avibactam plus Aztreonam resistance was reduced markedly among CRKP using the E-test. The addition of Aztreonam to ceftazidime/avibactam is an effective therapeutic option against MBL-producing K. pneumoniae.

Clinical Trials Registry: Pan African Clinical Trials Registry. Trial No.: PACTR202410744344899. Trial URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=32000