The US Centres for Disease Control and Prevention (CDC) has released the details of its investigation into the source of a multi-state outbreak of a deadly drug-resistant bacteria, which was linked to toxic “artificial tears” bought over the counter.
The carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa affected more than 80 patients, some of whom died while others went blind or had their eyes removed.
Carbapenems are a class of antibiotics that were developed to treat bacteria which are resistant to other drugs. Because of the overuse of these drugs, some types of Pseudomonas have developed resistance to carbapenems – these bacteria are called carbapenem-resistant Pseudomonas aeruginosa (CRPA).
The findings appeared in Clinical Infectious Diseases.
The investigation by researchers with the CDC, the Food and Drug Administration (FDA), and several state and local health departments, identified a total of 81 patients from 18 states in the outbreak, which stretched from May to November 2022 and was originally linked to an ophthalmology clinic in Los Angeles.
CIDRAP reports that nearly a third of the patients (26) were treated at one of three healthcare facilities in three states. Four of 54 case-patients with clinical cultures died within 30 days of culture collection, four of 18 patients with eye infections had to have their eyes removed, and an additional 14 suffered vision loss.
Overall, the use of artificial tears was reported by 61 of 70 case-patients with information, and 43 of 56 with brand information reported using Brand A – a preservative-free, over-the-counter (OTC) product manufactured in India.
A 1:1 case-control study conducted with 16 case-patients identified in the largest healthcare facility cluster found that cases had five times greater odds of exposure to artificial tears than controls (crude matched odds ratio [OR], 5.0; 95% confidence interval [CI], 1.1 to 22.8).
Trace-back investigation confirms source
Whole-genome sequencing of isolates from case-patients and opened and unopened Brand A bottles showed the isolates were genetically related, and an FDA inspection of the Brand A manufacturing site identified “multiple deficient practices” as the likely sources of contamination.
“The combination of epidemiology and laboratory evidence, including the close genetic relatedness of isolates from case-patients across multiple states and from unopened Brand A product, indicates Brand A artificial tears was the outbreak source,” the authors wrote.
They said proposed legislative changes by the FDA to strengthen regulatory requirements for sterile manufacturing facility inspection before the distribution of OTC products could help prevent similar outbreaks in the future.
Study details
Extensively drug-resistant pseudomonas aeruginosa outbreak associated with artificial tears
Marissa Grossman, Danielle Rankin, Elizabeth Nazarian, et al.
Published in Clinical Infectious Diseases on 5 February 2024
Abstract
Background
Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak.
Methods
Cases were defined as a US patient’s first isolation of P. aeruginosa sequence type 1203 with the carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to CDC between January 1, 2022–May 15, 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination.
Results
We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and four (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears compared to controls (crude matched OR: 5.0, 95% CI: 1.1, 22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. FDA inspection of the manufacturing plant identified likely sources of contamination.
Conclusions
A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the US. The clinical impacts from this outbreak underscore the need for improved requirements for US OTC product importers.
See more from MedicalBrief archives:
FDA warns of toxic eye drops, possible blindness
Three dead and eight blinded from contaminated eye drops
US recall on eye drops after severe drug-resistant infection