A closer look at ceftazidime-avibactam in real-world settings

Antibiotic misuse and overuse fuel mutations in bacteria, leading to drug-resistant “superbugs,” with terrifying aftermath. Without intervention, antimicrobial resistance could cause 10 million deaths annually by 2050.

Every year, from November 18–24, the World Antimicrobial Awareness Week highlights these risks and promotes innovative treatments, enhanced surveillance, and best-practice sharing among clinicians. This article offers insights on the use of the fixed-dose combination antibiotic ceftazidime-avibactam in daily hospital settings.

Multidrug-resistant pathogens
Multidrug-resistant (MDR) bacteria account for up to 45 percent of hospital deaths. The leading pathogens in resistance-related deaths were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa.

Ceftazidime-avibactam targets a broad-range of MDR gram-negative bacteria. In the EZTEAM study, researchers detailed its use, efficacy, and safety in combating MDR pathogens across 45 hospital sites in 11 European and Latin American (LATAM) countries. [Infect Dis Ther 2023;12:891-917]

Data from 569 hospitalized patients aged ≥18 years who were treated with at least one dose of ceftazidime-avibactam according to approved indication per country label were analysed.

Patients should have undergone microbiological testing within 5 days prior to starting ceftazidime-avibactam. Excluded from the study were those with prior exposure to ceftazidime-avibactam, including patients in compassionate care programmes.

Study outcomes
Out of 569 patients, 516 (90.7 percent) received ceftazidime-avibactam for ≥72 hours; others had <72 hours exposure. The results below pertain to 516 patients with ≥72 hours of ceftazidime-avibactam exposure.

Prior to initiating ceftazidime-avibactam, 397 patients (76.9 percent) received other antibiotics (meropenem, piperacillin-tazobactam, vancomycin).  Considering only gram-negative coverage, many patients (n=390, 75.7 percent) used ceftazidime-avibactam as a second-line treatment. Infections stemmed from intra-abdominal, urinary, respiratory, bloodstream, and other sources.

Klebsiella pneumoniae was the most common bacteria causing these infections, with two-thirds of microorganisms being MDR, particularly to carbapenems (89.3 percent).

In the latest sample taken before initiating ceftazidime-avibactam, 68.5 percent (364 out of 531) of gram-negative bacteria identified were MDR. In cUTI patients, 88.7 percent (94 out of 106) were MDR. These MDR isolates displayed resistance primarily against penicillin/beta-lactamase inhibitor (98 percent), cephalosporins (97.4 percent), fluoroquinolones (90.6 percent), carbapenems (89.3 percent), and aminoglycosides (65.1 percent).  For K. pneumoniae and Klebsiella spp. combined, 88.5 percent of all isolates and 92.4 percent of MDR isolates resisted carbapenems.

 

Although all patients had no prior exposure to ceftazidime-avibactam, 7.8 percent of the tested isolates were resistant to the antibiotic prior to its administration (mostly K. pneumoniae).

Beta-lactamases were detected in 72.3 percent (401/555) of the isolates tested. Notably, 21.9 percent (154 isolates) showed no beta-lactamase, while 13 percent (72 isolates) had multiple beta-lactamases.

Ninety percent of the patients in whom MBL-carrying bacteria were identified were treated with the combination of ceftazidime-avibactam and aztreonam.

Treatment success rate with ceftazidime-avibactam was 77.3 percent (88.3 percent among patients who had cUTI), regardless of first- or second-line treatment.

The in-hospital mortality rate was 23.1 percent, and adverse events were reported in a small percentage of patients (6 out of 569).

Key summary points
Treatment patterns:
•            Infection sources were intra-abdominal, urinary, respiratory, bloodstream infections, and other infections (approximately 20 percent each).
•            K. pneumoniae was the most common microorganism identified prior to initiating ceftazidime-avibactam (59.3 percent).
•            Ceftazidime-avibactam was primarily used as second-line treatment for gram-negative infections.
•            It was often given in combination with other antibiotics, in accordance with the approved prescribing information, with recommended dose adjustments for patients with renal impairment.

Clinical outcomes:
•            Treatment success was achieved in 77.3 percent of patients overall, and 88.3 percent among patients with cUTI.
•            In-hospital mortality rate was 23.1 percent.