Examining the Efficacy and Use of Ceftazidime-Avibactam for Multidrug-Resistant Infections

Ceftazidime-avibactam is being used to treat a range of difference multidrug-resistant infections across US medical centers, according to a new report in Open Forum Infectious Diseases.

A team of investigators retrospectively examined 203 adult patients between 2015 and 2019 at 6 US medical centers in order to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam for a range of multidrug-resistant, gram-negative infections. Ceftazidime-avibactam, which is a combination antimicrobial consisting of an antipseudomonal cephalosporin and a novel non- β-lactam β-lactamase inhibitor. Real-world analyses of the efficacy of ceftazidime-avibactam for multidrug resistant infections are limited, hence the need for the study, wrote the investigators.

The study authors only included the initial ceftazidime-avibactam course during their study period, where they collected demographic, clinical, microbiological and treatment data from the electronic medical records.

Almost half of the patients (45.8%) resided in skilled nursing facilities prior to hospital admissions or were transferred from outside hospitals. Additionally, a majority of the patients had a 90-day history of hospitalization or systemic antibiotic exposure (74.4% and 77.3%, respectively), the study authors noted. Half of the patients were categorized as having a high severity of illness at infection onset, residing in the ICU.

The most common infection sources the investigators included in their retrospective analysis were respiratory (37.3%), urinary (19.7%) and intra-abdominal (18.7%). A majority of the infections were hospital-acquired and had a median time from admission to infection onset of 3 days.

Ceftazidime-avibactam was used to treat 63 patients with Pseudomonas spp. infections, a majority of which had a respiratory tract source, the investigators learned. The most common reason for treatment with ceftazidime-avibactam in these cases was co-infection with multidrug-resistant infections and cefepime resistance, or failure in hospitals that did not carry ceftazidime on the formulary, the study authors explained.

Composite clinical failure and 30-day mortality occurred in 29.1% and 17.2% of patients, respectively, the investigators determined. From the group of 101 patients admitted from a home setting, 29 and 10 required new nursing home placement or inpatient rehabilitation following discharge, respectively.

The highest rates of clinical failure and 30-day mortality were recorded in patients with primary bacteremia (70% and 40%, respectively) and respiratory tract infection (42.1% and 27.6%, respectively) the investigators reported. The lowest rates were found among patients with intra-abdominal (13.2% and 5.3%, respectively) and urinary tract infections (15% and 7.5%, respectively).

In general, the introduction of ceftazidime-avibactam combination therapy did not impact overall clinical failure in the overall patient population, the study authors said, or even among high-risk subgroups including the primary bacteremia, respiratory tract source, or ICU residence at infection onset patients.

A potential drug-related adverse effect was observed in 17 patients, or 8.4%, the investigators said. Of those patients, 10 developed acute kidney injury while receiving ceftazidime-avibactam; 9 of those were receiving concomitant nephrotoxic agents around the same time of the event.

The investigators also noted 3 patients developed Clostridioides diff associated diarrhea (of whom 2 received ceftazidime-avibactam combination therapy). Furthermore, 2 patients had a rash and 1 patient each experienced a possible drug-related neutropenia and gastrointestinal intolerance.

“Antimicrobial resistance in gram-negative pathogens has now reached a critical point and many infections are no longer easily treated with carbapenems, the previous drugs of choice,” the study authors concluded. “We conducted this study to evaluate the epidemiology and outcomes of patients treated with ceftazidime-avibactam from across the US for a range of multidrug-resistant gram-negative pathogens. By some measures, ceftazidime-avibactam treatment appeared to be both effective and safe.”