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

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 has identified EzriCare artificial tears as a common exposure for many patients. CDC and FDA recommend clinicians and patients stop using and discard EzriCare Artificial Tears and two additional products made by the same manufacturer, Delsam Pharma’s Artificial Tears, and Delsam Pharma’s Artificial Ointment.

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 May 15, 2023, CDC, in partnership with state and local health departments, identified 81 patients in 18 states (CA, CO, CT, DE, FL, IL, NC, NJ, NM, NV, NY, OH, PA, SD, TX, UT, WA, WI) with VIM-GES-CRPA, a rare strain of extensively drug-resistant P. aeruginosa. This represents an increase of 13 patients since the last update. Among these 13 patients, 6 (46%) had specimens collected prior to the February 2, 2023, manufacturer recall of products associated with this outbreak. These cases were confirmed after the recall date due to the time it takes for testing to confirm the outbreak strain and because of retrospective reporting of infections. Of the 7 patients who had specimens collected after the recall, most either resided in long-term care facilities with other known cases or reported use of a recalled brand of artificial tears.

Dates of specimen collection were from May 2022 to April 2023. Patients were initially identified from cultures of sputum, bronchial wash, or tracheal aspirate (14); sites related to the eye (e.g., cornea, vitreous; 21); urine (13); other nonsterile sources (3); blood (3); and ear (1); and from rectal swabs (26) collected for surveillance. Adverse outcomes that were associated with clinical (non-surveillance) cultures and reported to public health include 14 patients with vision loss, an additional 4 patients with enucleation (surgical removal of eyeball), and 4 deaths within 30 days of VIM-GES-CRPA clinical culture collection.

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 by FDA identified bacterial contamination; further characterization of the contaminants is ongoing.

Three products have been voluntarily recalled by their manufacturer, Global Pharma (Chennai, India), in association with this outbreak: EzriCare Artificial Tears, Delsam Pharma Artificial Tears, and Delsam Pharma Artificial Ointment. No other products have been linked to this outbreak. Patients and healthcare providers should immediately stop using and discard EzriCare Artificial Tears, Delsam Pharma Artificial Tears, and Delsam Pharma Artificial Ointment.

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 and Delsam Pharma Artificial Ointment 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 or Delsam Pharma’s artificial eye ointment 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

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 healthcare 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 and discard EzriCare or Delsam Pharma’s Artificial Tears and Delsam Pharma Artificial Ointment. Instruct patients who are currently using these products to do the same. Facilities and/or providers who have already administered EzriCare or Delsam Pharma’s Artificial Tears or Delsam Pharma’s Artificial Ointment 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 or Delsam Pharma’s Artificial Ointment.

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

Summary of Recent Updates