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

Abstract

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.