The CDC and FDA have announced an outbreak of at least 15 Burkholderia cepacia infections associated with contaminated ultrasound gel used to guide invasive procedures as well as an unrelated outbreak of Burkholderia pseudomallei that caused two deaths.
The procedures involved in the B cepacia outbreak included placement of both central and peripheral intravenous catheters and paracentesis (removal of peritoneal fluid from the abdominal cavity). Cases have occurred in several states.
Further testing has shown the presence of Burkholderia stabilis, a member of B cepacia complex (Bcc), in four lots of unopened bottles of MediChoice M500812 ultrasound gel. Eco-Med Pharmaceuticals of Etobicoke, Ontario, Canada, the parent manufacturer, has issued a recall of MediChoice M500812 or Eco-Gel 200 with the following lot numbers: B029, B030, B031, B032, B040, B041, B048, B055. A similar outbreak occurred in Canada.
Some of these cases resulted in bloodstream infections. Further details are not yet available. Bcc infections have ranged from asymptomatic to life-threatening pneumonias, particularly in patients with cystic fibrosis. Other risk factors include immunosuppression, mechanical ventilation, and the use of other invasive venous or urinary catheters.
Kiran M. Perkins, MD, MPH, outbreak lead with the CDC’s Prevention Research Branch, told Medscape Medical News via email that automated systems such as Vitek might have trouble identifying the organism as “the system may only reveal the microbial species at the genus level but not at the species level, and/or it may have difficulty distinguishing between members of closely related group members.”
In the CDC’s experience, “most facilities do not conduct further species identification.” The agency added that it cannot tell if there has been any increase in cases associated with COVID-19, as they are not notifiable diseases and the “CDC does not systematically collect information on B cepacia complex infections.”
Rodney Rohde, PhD, professor and chair, Clinical Lab Science Program, Texas State University, San Marcos, told Medscape Medical News via email that Burkholderia‘s “detection in the manufacturing process is difficult, and product recalls are frequent.” He added, “A recent review by the Food and Drug Administration in the US found that almost 40% of contamination reports in both sterile and nonsterile pharmaceutical products were caused by Bcc bacteria.” Another problem is that they often create biofilms, so “they are tenacious environmental colonizers of medical equipment and surfaces in general.”
There have been many other outbreaks as a result to B cepacia complex. Because it is often in the water supply used in pharmaceutical manufacturing and is resistant to preservatives, the FDA cautions that it poses a risk of contamination in all nonsterile, water-based drug products.
Recalls included contaminated antiseptics, such as povidone iodine, benzalkonium chloride, and chlorhexidine gluconate. Contamination in manufacturing may not be uniform, and only some samples may be affected. Antiseptic mouthwashes have also been affected. So have nonbacterial soaps and docusate (a stool softener) solutions, and various personal care products, including nasal sprays, lotions, simethicone gas relief drops (Mylicon), and baby wipes.
Although Bcc are considered “objectionable organisms,” there have been no strong or consistent standards for their detection from the US Pharmacopeia (USP), and some manufacturers reportedly underestimate the consequences of contamination. The FDA issued a guidance to manufacturers in 2017 on quality assurance and cleaning procedures. This is particularly important since preservatives are ineffective against Bcc, and sterility has to be insured at each step of production.
Burkholderia isolates are generally resistant to commonly used antibiotics. Treatment might therefore include a combination of two drugs (to try to limit the emergence of more resistance) such as ceftazidime, piperacillin, meropenem with trimethoprim-sulfamethoxazole, or a beta-lactam plus aminoglycoside.
Interestingly, an outbreak of Burkholderia pseudomallei was just reported by the CDC as well. This is a related Gram-negative bacillus which is quite uncommon in the US. It causes melioidosis, usually a tropical infection, which presents with nonspecific symptoms or serious pneumonia, abscesses, or bloodstream infections.
Four cases have been identified this year in Georgia, Kansas, Minnesota, and Texas, two of them fatal. It is usually acquired from soil or water. By genomic analysis, the four cases are felt to be related, but no common source of exposure has been identified. They also appear to be closely related to South Asian strains, although none of the patients had traveled internationally. Prolonged antibiotic therapy with ceftazidime or meropenem, followed by 3-6 months of trimethoprim-sulfamethoxazole, is often required.
In his email, Rohde stated, “Melioidosis causes cough, chest pain, high fever, headache or unexplained weight loss, but it may take 2-3 weeks for symptoms of melioidosis to appear after a person’s initial exposure to the bacteria. So, one could see how this might be overlooked as COVID per symptoms and per the limitations of laboratory identification.”
It’s essential for clinicians to recognize that automated microbiology identification systems can misidentify B pseudomallei as B cepacia and to ask the lab for more specialized molecular diagnostics, particularly when relatively unusual organisms are isolated.
Candice Hoffmann, a public affairs specialist at the CDC, told Medscape Medical News, “Clinicians should consider melioidosis as a differential diagnosis in both adult and pediatric patients who are suspected to have a bacterial infection (pneumonia, sepsis, meningitis, wound) and are not responding to antibacterial treatment, even if they have not traveled outside of the continental United States.”
Rohde has disclosed no relevant financial relationships.
Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research , the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone .