Outbreak of Extensively Drug-resistant Pseudomonas aeruginosa Associated with Artificial Tears

Summary of Recent Updates

CDC is collaborating with the Food and Drug Administration (FDA) and state and local health departments to investigate a multistate outbreak of an extensively drug-resistant strain of Pseudomonas aeruginosa. The outbreak strain, carbapenem-resistant Pseudomonas aeruginosa with Verona integron-mediated metallo-β-lactamase and Guiana extended-spectrum-β-lactamase (VIM-GES-CRPA), had never been reported in the United States prior to this outbreak. The outbreak is associated with multiple types of infections, including eye infections. The investigation to date has identified artificial tears as a common exposure for many patients.

At this time, CDC and FDA recommend clinicians and patients stop using EzriCare or Delsam Pharma’s Artificial Tears products pending additional guidance from CDC and FDA.

Current Update

As of March 14, 2023, CDC, in partnership with state and local health departments, identified 68 patients in 16 states (CA, CO, CT, FL, IL, NC, NJ, NM, NY, NV, PA, SD, TX, UT, WA, WI) with VIM-GES-CRPA, a rare strain of extensively drug-resistant P. aeruginosa. Thirty-seven patients were linked to four healthcare facility clusters. Three people have died and there have been 8 reports of vision loss and 4 reports of enucleation (surgical removal of eyeball). Dates of specimen collection were from May 2022 to February 2023. Isolates have been identified from clinical cultures of sputum or bronchial wash (15), cornea (17), urine (10), other nonsterile sources (4), and blood (2), and from rectal swabs (26) collected for surveillance; some patients had specimens collected from more than one anatomic site.

Most patients reported using artificial tears. Patients reported over 10 different brands of artificial tears and some patients used multiple brands. EzriCare Artificial Tears, a preservative-free, over-the-counter product packaged in multidose bottles, was the brand most commonly reported. This was the only common artificial tears product identified across the four healthcare facility clusters. Laboratory testing by CDC identified the presence of VIM-GES-CRPA in opened EzriCare bottles from multiple lots; these bottles were collected from patients with and without eye infections and from two states. VIM-GES-CRPA recovered from opened products match the outbreak strain. Testing of unopened bottles of EzriCare Artificial Tears is ongoing to assist in evaluating for whether contamination may have occurred during manufacturing. Patients and healthcare providers should immediately stop the use of EzriCare Artificial Tears pending additional information and guidance from CDC and FDA.

FDA encourages health care professionals and patients to report adverse events or quality problems with any medicine to FDA’s MedWatch Adverse Event Reporting program. Consumers may also report adverse reactions by contacting FDA’s Consumer Complaint Coordinators.

Patient Information

Patients should stop using EzriCare or Delsam Pharma’s Artificial Tears pending additional information and guidance from CDC and FDA. If patients were advised to use EzriCare or Delsam Pharma’s Artificial Tears by their healthcare provider, they should follow up with their healthcare provider for recommendations about alternative treatment options.

Patients who have used EzriCare or Delsam Pharma’s artificial tears and who have signs or symptoms of an eye infection should seek medical care immediately. At this time, there is no recommendation for testing of patients who have used this product and who are not experiencing any signs or symptoms of infection.

Eye infection symptoms may include:

• Yellow, green, or clear discharge from the eye
• Eye pain or discomfort
• Redness of the eye or eyelid
• Feeling of something in your eye (foreign body sensation)
• Increased sensitivity to light
• Blurry vision

FDA encourages health care professionals and patients to report adverse events or quality problems with any medicine to FDA’s MedWatch Adverse Event Reporting program. Consumers may also report adverse reactions by contacting FDA’s Consumer Complaint Coordinators.

Clinician Information

Facilities and/or providers should discontinue use of EzriCare or Delsam Pharma’s Artificial Tears and instruct patients who are currently using EzriCare or Delsam Pharma’s Artificial Tears to stop using the product pending additional guidance from CDC and FDA. Facilities and/or providers who have already administered EzriCare or Delsam Pharma’s Artificial Tears to their patients should monitor for signs and symptoms of infection and perform culture and antimicrobial susceptibility testing when clinically indicated. Healthcare providers treating patients for keratitis or endophthalmitis should ask patients if they have used EzriCare or Delsam Pharma’s Artificial Tears.

Based on susceptibility information from isolates collected as part of this investigation, this strain of P. aeruginosa was not susceptible to cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, carbapenems, ceftazidime-avibactam and ceftolozane-tazobactam, fluoroquinolones, polymyxins, amikacin, gentamicin, and tobramycin. A subset of 3 isolates that underwent antimicrobial susceptibility testing for cefiderocol at clinical laboratories or CDC were susceptible to this agent. Healthcare providers treating VIM-GES-CRPA infections should consult with a specialist knowledgeable in the treatment of antibiotic-resistant bacteria to determine the best treatment option.

Healthcare providers caring for patients with VIM-producing P. aeruginosa should follow infection control recommendations listed below to prevent transmission to other patients, as these bacteria have the potential to spread rapidly in healthcare settings.

When new VIM-CRPA are identified in inpatient or long-term care settings:

• Work with the clinical laboratory and Antimicrobial Resistance Laboratory Network to further characterize the isolate to determine whether it matches the outbreak strain. Facilities and providers should report CRPA from an ocular specimen or VIM-CRPA from any specimen source with collection dates since January 1, 2022, to your local or state public health departments and ask clinical laboratories to save these isolates for further characterization at public health laboratories.
• Follow the Interim Guidance for a Public Health Response to Contain Novel or Targeted Multidrug-resistant Organisms (MDROs) recommendations for Tier 2 organisms to evaluate for further spread, including:
  • Perform colonization screening of healthcare contacts of patients with VIM-CRPA
  • Perform laboratory lookbacks for other CRPA
  • Conduct prospective surveillance for new cases of CRPA, and submit isolates to public health laboratories for carbapenem resistance mechanism testing
  • Place patients infected or colonized with VIM-CRPA admitted to acute care settings in isolation and use Contact Precautions. For residents of skilled nursing facilities who are infected or colonized with VIM-CRPA, use Enhanced Barrier Precautions if the resident does not have an indication for Contact Precautions.

Clinical Laboratory Information

Clinical laboratories that identify P. aeruginosa resistant to imipenem or meropenem are encouraged to perform carbapenem resistance mechanism testing. Isolates may also be submitted to the Antimicrobial Resistance Laboratory Network for mechanism testing. Laboratories wishing to apply a more specific definition when identifying isolates that might be related to this cluster for mechanism testing could limit testing to CRPA that are also resistant to cefepime, ceftazidime, and (if tested) ceftazidime-avibactam and ceftolozane-tazobactam.

Clinical laboratories that identify any CRPA from an ocular specimen or VIM-CRPA from any specimen source should submit the isolate to the Antimicrobial Resistance Laboratory Network for further characterization. Please reach out to your health department’s healthcare-associated infections contact or email haioutbreak@cdc.gov for assistance submitting isolates.

Clinical laboratories that perform whole genome sequencing (WGS) and identify P. aeruginosa ST1203 with bla_VIM-80 and bla_GES-9 should report cases to the health department’s healthcare-associated infections program contact (https://www.cdc.gov/hai/state-based/index.html) or CDC as soon as possible.

Additional Resources

FDA warns consumers not to purchase or use EzriCare Artificial Tears due to potential contamination | FDA Global Pharma’s voluntary recall notice

Global Pharma’s voluntary recall notice

Health Alert Network (HAN) No. 485 – Outbreak of Extensively Drug-resistant Pseudomonas aeruginosa associated with Artificial Tears

Pseudomonas aeruginosa in Healthcare Settings

Combatting Antimicrobial Resistance, a global threat

Containment Strategy Responding to Emerging AR Threats

About the AR Lab Network