CDC HAN (Advisory): Outbreak of Extensively Drug-resistant Pseudomonas aeruginosa Associated with Artificial Tears

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Late yesterday the CDC released a HAN (Health Alert Network) advisory on an outbreak of a extensively drug resistant bacterial infection (Pseudomonas aeruginosa) which is linked to the use of artificial tears. 

Two weeks ago, the CDC announced they were investigating an outbreak (see below), which spanned several states and had resulted in at least one death. 

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 to date has identified artificial tears as a common exposure for many patients.

At this time, CDC recommends clinicians and patients stop using EzriCare Artificial Tears products pending additional guidance from CDC and FDA.

Clinicians: Please report any carbapenem-resistant Pseudomonas aeruginosa (CRPA) from an ocular specimen or VIM-CRPA from any specimen source with collection dates since January 1, 2022, to your local or state health department’s healthcare-associated infections contact or email haioutbreak@cdc.gov for assistance submitting specimens. Ask your clinical laboratories to save these isolates for further characterization at public health laboratories.

The CDC describes drug-resistant Pseudomonas as:

What is drug-resistant Pseudomonas?

Pseudomonas is a kind of bacteria found widely in the environment. The most common type of Pseudomonas that infects humans is called Pseudomonas aeruginosa. Pseudomonas infections of the blood, lungs (pneumonia), and after surgery can lead to severe illness and death.

Unfortunately, bacteria (including Pseudomonas) are becoming more resistant to antibiotics. Infections with bacteria that are resistant to antibiotics are much harder to treat. Bacteria that cause infections that doctors cannot treat easily with antibiotics are called “drug-resistant.” Drug-resistant Pseudomonas bacteria do not respond to most commonly available antibiotics. 

New resistant strains of Pseudomonas continues to emerge (see 2019's CDC Traveler's Advisory: Drug-Resistant Pseudomonas aeruginosa Infections In Mexico) and its incidence has reportedly worsened during the pandemic (see CDC: COVID-19 Reverses Progress in Fight Against Antimicrobial Resistance in U.S.). 

In the report, CDC analyzed the state of antimicrobial resistance in the United States immediately following the 2020 peaks of the COVID-19 pandemic. The data show an alarming increase in resistant infections starting during hospitalization, growing an overall 15% from 2019 to 2020 among seven pathogens. Increases in specific pathogens included:

• carbapenem-resistant Acinetobacter – 78% increase in infections,
• multidrug-resistant Pseudomonas aeruginosa – 32% increase in infections,
• vancomycin-resistant Enterococcus (VRE) – 14% increase in infections, and
• methicillin-resistant Staphylococcus aureus (MRSA) – 13% increase in infections

The strain of drug resistant Pseudomonas aeruginosa reported in this latest outbreak had never been reported in the United States previously. 

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

Distributed via the CDC Health Alert Network
February 1, 2023, 7:00 PM ET
CDCHAN-00485

Summary

The Centers for Disease Control and Prevention (CDC) is issuing this Health Alert Network (HAN) Health Advisory about infections with an extensively drug-resistant strain of Verona Integron-mediated Metallo-β-lactamase (VIM) and Guiana-Extended Spectrum-β-Lactamase (GES)-producing carbapenem-resistant Pseudomonas aeruginosa (VIM-GES-CRPA) in 12 states. Most patients reported using artificial tears. Patients reported more than 10 different brands of artificial tears, and some patients used multiple brands. The majority of patients who used artificial tears reported using EzriCare Artificial Tears, a preservative-free, over-the-counter product packaged in multidose bottles. CDC laboratory testing identified the presence of the outbreak strain in opened EzriCare bottles with different lot numbers collected from two states. Patients and healthcare providers should immediately discontinue using EzriCare artificial tears pending additional guidance from CDC and the Food and Drug Administration (FDA).

Background

As of January 31, 2023, CDC in partnership with state and local health departments identified 55 case-patients in 12 states (CA, CO, CT, FL, NJ, NM, NY, NV, TX, UT, WA, WI) with VIM-GES-CRPA, a rare strain of extensively drug-resistant P. aeruginosa. Thirty-five patients are linked to four healthcare facility clusters. Dates of specimen collection were from May 2022 to January 2023. Isolates have been identified from clinical cultures of sputum or bronchial wash (13), cornea (11), urine (7), other nonsterile sources (4), blood (2), and from rectal swabs (25) collected for surveillance; some patients had specimens collected from more than one anatomic site. These specimens were collected in both outpatient and inpatient healthcare settings. Patients had a variety of presentations including keratitis, endophthalmitis, respiratory infection, urinary tract infection, and sepsis. Patient outcomes include permanent vision loss resulting from cornea infection, hospitalization, and one death due to systemic infection.

Isolates in this outbreak are sequence type (ST) 1203, harbor blaVIM-80 and blaGES-9 (a combination not previously observed in the United States) and are closely related based on analysis of whole genome sequencing (WGS) data. These isolates are not susceptible to cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, fluoroquinolones, polymyxins, amikacin, gentamicin, and tobramycin; the subset of isolates that underwent antimicrobial susceptibility testing for cefiderocol were susceptible to this agent.

Review of common exposures revealed that most patients, including most patients with eye infections, used artificial tears prior to identification of VIM-GES-CRPA infection or colonization. Patients reported more than 10 brands of artificial tears, and some patients used multiple brands. The majority of patients who used artificial tears reported using EzriCare Artificial Tears, a preservative-free product dispensed in multidose bottles. This was the only common artificial tears product identified across the four healthcare facility clusters. CDC laboratory testing identified the presence of VIM-GES-CRPA in opened EzriCare Artificial Tears bottles from multiple lots; these bottles were collected from patients with and without eye infections in two states. These product-related VIM-GES-CRPA match the outbreak strain. VIM-GES-CRPA recovered from opened bottles could represent either bacterial contamination during use or during the manufacturing process. Testing of unopened bottles of EzriCare Artificial Tears is ongoing to assist in evaluating for whether contamination may have occurred during manufacturing.

Recommendations for Healthcare Providers

• Immediately discontinue using EzriCare Artificial Tears pending additional guidance from CDC and FDA.
• Advise patients who used EzriCare Artificial Tears to monitor for signs and symptoms of infection. 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 Artificial Tears. Providers should consider performing culture and antimicrobial susceptibility testing to help guide therapy if patients report use of this product.
• 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. VIM-GES-CRPA isolates associated with this outbreak are extensively drug-resistant. Isolates that underwent susceptibility testing at public health laboratories were not susceptible to cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, carbapenems, ceftazidime-avibactam, 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.
• Place patients infected or colonized with VIM-GES-CRPA and admitted to acute care settings in isolation and use Contact Precautions. For residents of skilled nursing facilities who are infected or colonized with VIM-GES-CRPA, use Enhanced Barrier Precautions if the resident does not have an indication for Contact Precautions.
• At this time, CDC does not recommend testing patients who have used this product and who are not experiencing any signs or symptoms of infection.

Recommendations for Clinical Laboratories

• 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 carbapenem-resistant P. aeruginosa that are also resistant to cefepime, ceftazidime, and (if tested) ceftazidime-avibactam and ceftolozane-tazobactam.
• Clinical laboratories that identify any carbapenem-resistant P. aeruginosa 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.

Recommendations for the Public

• Discontinue using EzriCare Artificial Tears pending additional guidance from CDC and FDA.
• If patients were advised to use EzriCare Artificial Tears by their healthcare provider, they should follow up with their healthcare provider for an alternative artificial tears product to use.
• Patients who used EzriCare Artificial Tears and who have signs or symptoms of an eye infection, such as discharge from the eye, eye pain or discomfort, redness of the eye or eyelid, feeling of something in the eye, increased sensitivity to light, or blurry vision, should seek timely medical care. At this time, CDC does not recommend testing of patients who have used this product and who are not experiencing any signs or symptoms of infection.

(Continue . . )

Each year it seems as if we draw a little closer to a predicted, and highly plausible `post-antibiotic era', where even common infections become resistant to most antibiotics, and something as simple as a scraped knee, or elective surgery, could be deadly.

While antibiotics still work today for most infections, for tens of thousands of people every year, that `post-antibiotic era' is already here.

While I cover AMR topics from time to time in this blog, I can heartily recommend CIDRAP's Antimicrobial Stewardship Project as the best place to learn about the growing global threat of AMR.