Outbreak Identification and Early Epidemiologic Investigation
On September 28, 2018, the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) received a report from the Arizona Department of Health Services of VIM-CRPA cultured from an abdominal wound of a 31-year-old patient on September 5, 2018. Initial investigation determined the patient underwent bariatric surgery in Tijuana, Mexico, 15 days before specimen collection. From late September through late November 2018, CDC received 6 reports of VIM-CRPA isolates from patients who underwent bariatric surgery in Tijuana. Four patients used the same US-based travel agency (travel agency A), which coordinated travel and arranged care for medical tourists; all 4 patients reported undergoing bariatric surgery at the same facility in Tijuana (facility A) with the same surgeon (surgeon 1).
In response, CDC and the Secretariat of Health in Baja California, Mexico, launched a public health investigation. On November 19, 2018, CDC issued a call for cases on the Epidemic Information Exchange (https://www.emergency.cdc.gov/epix/index.asp) for P. aeruginosa isolated from patients reporting bariatric surgery in Tijuana since August 1, 2018; CDC also posted an Emerging Infections Network notification on November 23, 2018. The Federal Commission for Protection against Sanitary Risk in Mexico conducted an infection control assessment of facility A in December 2018 and identified multiple lapses, including poor hand hygiene practices, incomplete clinical records, and lack of chemical or biologic indicators to ensure medical equipment and device sterility after reprocessing. The lack of indicators potentially exposed patients to risk for infections with bloodborne pathogens, such as HIV and hepatitis B and C viruses, in addition to bacterial infections. On the basis of these findings, the Secretariat of Health issued a closure order for the surgical suite at facility A on December 17, 2018, and CDC issued an Alert Level 2 Travel Health Notice during January 2019, advising US residents against undergoing surgery at Facility A (Appendix, https://wwwnc.cdc.gov/EID/article/28/1/21-1880-App1.pdf).
A confirmed case was isolation of VIM-CRPA from a patient who had an elective invasive medical procedure in Mexico during January 2018–December 2019 and within 45 days before specimen collection. A probable case was isolation of CRPA, with the isolate unavailable for carbapenemase testing, from a patient who had an elective invasive medical procedure in Mexico during January 2018–December 2019 and within 45 days before specimen collection. A suspect case was infection (subjective or measured fever and ≥2 of the following at incision sites: pus; fluid draining; or warmth, redness and swelling) within 45 days of surgery in a patient who had surgery at facility A during January 2018–December 2019 and sought medical care but did not have a culture collected.
Passive Case Finding
CRPA are routinely submitted from clinical laboratories to the Antibiotic Resistance Laboratory Network, a US national network of 55 public health laboratories performing carbapenemase testing for carbapenem-resistant organisms. There is no national requirement to report or submit CRPA for carbapenem resistance mechanism testing, and isolate submission strategies differ by state. CDC guidance for containing spread of emerging and targeted MDR organisms recommends state and local health departments investigate reports of novel or targeted carbapenemase-producing organisms, including CP-CRPA. After the initial cluster was identified, health departments investigating cases in persons who reported surgery in Tijuana attempted to obtain the names of healthcare facilities, surgeons, and travel agencies used by case-patients; the type of surgery performed; and whether the case-patient was subsequently admitted to a US healthcare facility. During some case investigations, case-patients reported knowing other sick persons who underwent surgery; state and local health departments attempted to contact these persons and review medical records for those who reported signs or symptoms of infection.
Patient Notification and Active Case Finding
Because names of persons who underwent surgery at facility A were not initially available, in January 2019, CDC posted an online notification for patients and their US healthcare providers (https://www.cdc.gov/hai/outbreaks/pseudomonas-aeruginosa.html) and an Alert Level 2 Travel Health Notice (Appendix), both of which were covered by major media outlets.[22–24] Notifications provided warning of postoperative bacterial infection risk and potential for bloodborne pathogen transmission. Individual states also issued Health Alert Network notices to increase awareness of potential cases. During March 2019, travel agency A sent an electronic notification regarding potential exposures to clients who had surgery at facility A during August 1, 2018–February 15, 2019, and provided CDC with contact information for persons referred to facility A during August 1, 2018–March 1, 2019.
We classified persons who had surgery on or after January 1, 2019, as higher risk for new onset or ongoing postoperative infections; persons who had surgery before January 1, 2019, were classified as lower risk because of the longer elapsed time since surgery. For higher risk persons, CDC and state and local health departments conducted telephone notifications and structured interviews to obtain demographics, clinical and exposure details, and information about factors influencing their decision to have surgery at facility A (Appendix). In addition to the travel agency A client notification and CDC and online notification, CDC recommended state and local public health officials send notification letters to lower risk persons; some health jurisdictions additionally performed active outreach for these persons. Contact information for non-US residents was shared with respective public health agencies. For case-patients admitted to US healthcare facilities, responses were conducted by health departments to assess for transmission (https://www.cdc.gov/hai/containment/guidelines.html).
Molecular Typing and Antimicrobial Drug Susceptibility Testing
VIM-CRPA isolates underwent whole-genome sequencing (WGS) and analysis at CDC and state health departments. WGS libraries were prepared by using the NuGEN Ovation Ultralow System V2 Assay Kit (NuGen Technologies, https://www.nugentechnologies.co.za) and sequenced by using the MiSeq Reagent Kit v2 (500 cycle) (https://www.illumina.com) and the MiSeq System (Illumina), generating 2 × 250 paired-end reads. CDC processed and analyzed all sequences by using bioinformatics pipeline QuAISAR-H (quality, assembly, species identification, sequence typing, annotation, resistance mechanisms for healthcare pathogens) (https://github.com/DHQP/QuAISAR_singularity) and assessed phylogeny by using a core genome multilocus sequence type scheme for P. aeruginosa and SNVPhyl.[25–27]
Antimicrobial susceptibility testing for 15 drugs was performed at CDC by using frozen broth microdilution panels prepared according to Clinical and Laboratory Standards Institute reference methods. MICs were interpreted as susceptible, intermediate, or resistant according to Clinical and Laboratory Standards Institute definitions. We classified isolates as MDR or XDR by using published definitions.
We analyzed epidemiologic data by using R statistical software version 3.5.2 (R Foundation for Statistical Computing, https://cran.r-project.org). We estimated the VIM-CRPA attack rate by using data from the higher risk group (patients who had surgery during January–March 2019) with confirmed and probable cases from clinical cultures from patients who underwent surgery at facility A as the numerator and total patients referred by travel agency A to facility A as the denominator. We limited epidemiologic analyses to probable and confirmed cases.
This project was reviewed by human subjects advisors in the National Center for Emerging and Zoonotic Infectious Diseases at CDC and received a nonresearch determination and emergency approval by the Office of Management and Budget (OMB Control No. 0920–1253). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. All patients who participated in the structured interviews provided informed consent.
Emerging Infectious Diseases. 2022;28(1):51-61. © 2022 Centers for Disease Control and Prevention (CDC)