New research conducted by the Centers for Disease Control and Prevention (CDC), published in Clinical Infectious Diseases, investigated the outbreak of an antibiotic-resistant form of Pseudomonas (P.) aeruginosa previously linked with a multistate outbreak of artificial tear-associated patient cases reported last year.
First, explain this bacteria.
In carbapenemase-producing, carbapenem-resistant P. aeruginosa (CP-CRPA), pseudomonas produce enzymes called carbapenemases that break down antibiotics (such as carbapenems) and, as a result, are typically resistant to antibiotics.
In healthcare settings, the bacteria has been noted as a common cause of infections leading to pneumonia, bloodstream infections, urinary tract infections, and surgical site infections, according to the CDC.
See here for additional info, including how to identify patients with CRPA and steps to take for preventing transmission.
Now, let’s take a trip down memory lane …
Back in January 2023, the CDC recommended an immediate discontinuation of artificial tear eye drops due to an outbreak of CP-CRPA that was connected to the use of 10 different brands of over-the-counter (OTC) artificial tears, including EzriCare Artificial Tears (manufactured by India-based Global Pharma Healthcare Private Limited.)
A voluntary recall for EzriCare was then escalated to a Health Alert Network (HAN) Advisory in February 2023 that mandated all eye care practitioners (ECPs) and patients immediately stop use of the eye drops.
Also of note, a recall was issued for Delsam Pharma LLC’s artificial tears, as well as its artificial ointment.
In May 2023, the CDC confirmed 81 cases across 18 states, with four deaths, 14 reports of vision loss, and four reports of enucleation.
And in June 2023, Glance reported on the growing number of class-action and individual injury lawsuits that ensued as a result.
Gotcha. So what did this investigation entail?
Investigators from the CDC, FDA, and multiple state / local health departments identified those 81 cases (with 27 identified via surveillance cultures) of CP-CRPA between May to November 2022.
Per the study, they collected opened and unopened artificial tears products identified in the epidemiologic investigation from case-patient homes, healthcare facilities, distribution centers, and pharmacies.
From there, the original outbreak was traced back to a single ophthalmology clinic in Los Angeles, California, where a significant number of affected patients were treated.
Then what?
A 1:1 case-control study was conducted, with the randomly-selected controls being matched to cases based on facility and unit location.
Controls were required to have three criteria, including no history of P. aeruginosa culture results since April 1, 2022, that were resistant to carbapenems and not susceptible to two antibiotics: cefepime or ceftazidime.
The investigators then examined exposures associated with case status for all case-patients, testing products for bacterial contamination.
And their findings?
Based on the case-control study, case-patients had an increased odds of receiving artificial tears vs their controls: (crude matched OR: 5.0, 95% Confidence Interval (CI): 1.1, 22.8)
Give me specifics.
According to the investigators:
- 87% (61) of 70 case-patients reported artificial tear use (with no specific brand mentioned)
- 77% (43) of 50 case-patients with brand information reported use of Brand A (EzriCare Artificial Tears)
Bacteria that were “isolated from opened and unopened bottles of Brand A were genetically related to [the case-patient] isolates,” the authors wrote.
Further, an FDA inspection of Brand A’s manufacturing plant (Global Pharma Healthcare) “also identified likely sources of contamination.”
Meaning?
Whole-genome sequencing of the case-patients’ isolates with Brand A’s bottles revealed that the contamination originated from the artificial tear’s manufacturing plan.
Translation: The investigators confirmed that the bacteria contamination linked to EzriCare Artificial Tears came from Global Pharma’s manufacturing plant.
And what’s the significance of this?
Per the investigators, such an incidence—with a manufactured medical product serving as a vehicle for such bacterial strains as CR-CPA—”is unprecedented in the U.S.”They concluded: The clinical impacts from this outbreak underscore the need for improved requirements for U.S. OTC product importers.