Rapid Molecular Tests Can Aid Empiric Therapy Decisions in P aeruginosa Cases

Scientists sought to figure out whether rapid diagnostic tests could be used to determine the susceptibility of P aeruginosa to 2 new therapies. The answer was yes, but with caveats.

New research suggests rapid molecular diagnostics (RMDs) could play a helpful role in informing empiric therapy selection for patients with Pseudomonas aeruginosa infection, though the investigators say the method has significant limitations.

P aeruginosa is a common cause of hospital-acquired infections (HAI), with about 50,000 cases reported in the United States each year.

The new research is an effort to determine whether rapid molecular diagnostic tests could help clinicians determine if a particular patient’s infection is susceptible to 2 new combinations of beta-lactam/beta-lactamase inhibitors, ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (TOL/TAZO).

Those 2 combinations are critical because P aeruginosa is increasingly becoming resistant to current therapies like imipenem, meropenem, piperacillin/tazobactam, ceftazidime, and cefepime. Monitoring agencies say isolates from hospital intensive care units, in particular, are showing increased resistance.

That’s distressing to lead author Scott R. Evans, PhD, MS, of George Washington University, and his colleagues who worked on the study.

“Losing the ability to empirically or definitely administer these ‘last line’ drugs creates a distressing clinical situation as alternatives (e.g., polymyxins) may be toxic, difficult to monitor, and have challenging pharmacokinetic properties,” write Dr. Evans and colleagues.

Thus, being able to administer newer therapies like CZA and TOL/TAZO would be a big deal, particularly if they could be administered in a targeted manner, only to patients for whom the therapies were likely to work.

To find out if that’s possible, investigators used 2 RMDs (Acuitas Resistome Test and VERIGENE Gram-Negative Blood Culture Test) to evaluate 197 P aeruginosa isolates, including multidrug-resistant isolates. The goal was to see whether the tests could accurately predict susceptibility to CZA and TOL/TAZO.

The answer was yes, but with caveats.

The research showed that the tests correctly identified susceptibility to both CZA and TOL/TAZO, with 100% susceptibility sensitivity. However, the tests’ ability to determine resistance to CZA and TOL/TAZO was lower—66% resistance sensitivity for TOL/TAZO and 33% resistance sensitivity for CZA.

“The diagnostic platforms studied showed the most potential in scenarios where a resistance gene was detected or in scenarios where a resistance gene was not detected and the prevalence of resistance to TOL/TAZO or CZA is known to be low,” the authors conclude.

Thus, in areas with high susceptibility to the 2 therapies, the susceptibility predictive values of the tests would be very high—97% or greater. However, resistance predictive values would be much lower. In areas or time periods where resistance was known to be high, susceptibility and resistance predictive values would be in the high 80% to low 90% range.

Thus, the investigators argue, while rapid molecular diagnostics can be helpful, they need to be treated as just 1 factor in a complicated decision.

“Clinicians need to be mindful of the benefits and risks resulting from empiric treatment decisions based on resistance gene detection in P aeruginosa, acknowledging that such decisions are impacted by the prevalence of resistance which varies temporally and geographically,” Dr. Evans and colleagues write.