October 2024

OCTOBER 2024

Official Publication of SDCMS

THE

ISSUE Latest Developments on Infectious Diseases

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Contents OCTOBER

Editor: James Santiago Grisolia, MD Editorial Board: James Santiago Grisolia, MD; David E.J. Bazzo, MD; William T-C Tseng, MD; Holly B. Yang, MD, MSHPEd, HMDC, FACP, FAAHPM Marketing & Production Manager: Jennifer Rohr Art Director: Lisa Williams Copy Editor: Adam Elder

VOLUME 111, NUMBER 9

OFFICERS President: Steve H. Koh, MD President–Elect: Preeti S. Mehta, MD Immediate Past President: Nicholas (dr. Nick) J. Yphantides, MD, MPH Secretary: Maria T. Carriedo-Ceniceros, MD Treasurer: Karrar H. Ali, DO, MPH GEOGRAPHIC DIRECTORS East County #1: Catherine A. Uchino, MD East County #2: Rachel Van Hollebeke, MD Hillcrest #1: Kyle P. Edmonds, MD Hillcrest #2: Stephen R. Hayden, MD (Delegation Chair) Kearny Mesa #1: Anthony E. Magit, MD, MPH Kearny Mesa #2: Dustin H. Wailes, MD La Jolla #1: Toluwalase (Lase) A. Ajayi, MD La Jolla #2: David E.J. Bazzo, MD, FAAFP North County #1: Arlene J. Morales, MD (Board Representative to the Executive Committee) North County #2: Christopher M. Bergeron, MD, FACS North County #3: Nina Chaya, MD South Bay #1: Paul J. Manos, DO South Bay #2: Latisa S. Carson, MD AT–LARGE DIRECTORS #1: Rakesh R. Patel, MD, FAAFP, MBA (Board Representative to the Executive Committee) #2: Kelly C. Motadel, MD, MPH #3: Irineo (Reno) D. Tiangco, MD #4: Miranda R. Sonneborn, MD #5: Daniel D. Klaristenfeld, MD #6: Alexander K. Quick, MD #7: Karl E. Steinberg, MD, FAAFP #8: Alejandra Postlethwaite, MD ADDITIONAL VOTING DIRECTORS Young Physician: Emily A. Nagler, MD Retired Physician: Mitsuo Tomita, MD Medical Student: Kenya Ochoa CMA OFFICERS AND TRUSTEES Trustee: William T–C Tseng, MD, MPH Trustee: Sergio R. Flores, MD Trustee: Timothy A. Murphy, MD AMA DELEGATES AND ALTERNATE DELEGATES District I: Mihir Y. Parikh, MD District I Alternate: William T–C Tseng, MD, MPH At–Large: Albert Ray, MD At–Large: Robert E. Hertzka, MD At–Large: Theodore M. Mazer, MD At–Large: Kyle P. Edmonds, MD At–Large: Holly B. Yang, MD, MSHPEd, HMDC, FACP, FAAHPM At–Large: David E.J. Bazzo, MD, FAAFP At–Large Alternate: Sergio R. Flores, MD At–Large Alternate: Bing Pao, MD CMA DELEGATES District I: Steven L.W. Chen, MD, FACS, MBA District I: Vikant Gulati, MD District I: Eric L. Rafla-Yuan, MD District I: Ran Regev, MD District I: Quinn Lippmann, MD District I: Kosala Samarasinghe, MD District I: Thomas J. Savides, MD District I: Mark W. Sornson, MD District I: Wynnshang (Wayne) C. Sun, MD District I: Patrick A. Tellez, MD, MHSA, MPH District I: Randy J. Young, MD

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FEATURES

2

Cell-Free DNA Plasma Next-Generation Sequencing Test: The UCSD Experience

By Sean Jung, MD, MPH, Ahnika Kline, MD, PhD, D (ABMM), Shira Abeles, MD, and Francesca Torriani, MD, FIDSA, AAHIVS

6

Chagas Disease Is Now Reportable in San Diego County: What You Need to Know

By Meghan Villalobos, MPH, Audrey Kennar, MSPH, BSN, RN, Mark Beatty, MD, MPH, and Paula Stigler Granados, PhD, MS

10

County of San Diego One Health Epidemiology Program – Links Human and Animal Health

By Emily Trumbull, DVM, Sarah Stous, MPH, Julie Breher, DVM, MPVM, Catherine Blaser, MPH, RN, PHN, ACRN, CIC, Erik A. Berg, MD, Mark Beatty, MD, MPH, Jeffrey Johnson, MPH, and Seema Shah, MD, MPH

14

The Art of Managing Gram-Negative Resistance: Key Updates on PracticeChanging Guidance

By Victor Chen, PharmD, Christopher Baladad, PharmD, Helen Berhane, PharmD, Nina Haste, PharmD, PhD, Nancy Law, DO, and Shira Abeles, MD

18

Candida Auris in San Diego: Enhancing Infection Prevention and Control Efforts

By Loriel Magsino, MPH, CIC and Francesca J. Torriani, MD, FIDSA, AAHIVS

DEPARTMENTS

21

Classifieds SANDIEGOPHYSICIAN.ORG

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INFEC TIOUS DISE A SES

Cell-Free DNA Plasma NextGeneration Sequencing Test: The UCSD Experience Is It Worth the Cost? By Sean Jung, MD, MPH, Ahnika Kline, MD, PhD, D (ABMM), Shira Abeles, MD, and Francesca Torriani, MD, FIDSA, AAHIVS Introduction Approximately 1,400 microorganisms are known to cause human disease1, resulting in more than 10 million outpatient visits and 482,000 hospital admissions in the United States2.

Early pathogen identification is critical to targeting effective therapy and fewer adverse events, but identification of the causative pathogen remains challenging in many clinical scenarios despite advancements in molecular diagnostics.

With the refinement of genomic medicine, we have witnessed transformative advancements in next-generation sequencing (NGS) technologies. This incredible advancement is having a profound impact in all areas of medicine — diagnosis of infectious diseases is one of them when traditional methods fail to identify organisms3.

In the rapidly evolving field of genomics and diagnostics, various NGS technologies offer distinct advantages for analyzing complex biological samples. There are three distinct approaches when applying NGS technologies for the diagnosis diagnose infectious diseases: whole-genome sequencing, targeted NGS, and metagenomic NGS. Each method provides unique insights into microbial communities and infectious diseases, and understanding their differences can guide clinicians in selecting the most appropriate diagnostic tool.

However, that is beyond the scope of this brief article; we will focus on KariusDx’s cfDNA NGS (KT).

Sequencing of cfDNA has recently been shown to have clinical utility, especially in infections among pediatric populations, immunocompromised patients with infections caused by fastidious or slow-growing organisms like fungi or mycobacterium, or for molecular diagnostics of deep-seated infections that would otherwise require invasive procedures for diagnosis5. Clinical evidence is building, and more than 300 articles are available as clinical data, though results from randomized clinical trials are scarce6. KT represents a distinct approach that analyzes cell-free DNA fragments circulating in the bloodstream. This method has unique features and applications, including non-invasiveness and broad pathogen detection. However, KT may face challenges related to the quality of the sample, the potential for false positives or negatives, the lack of utility for RNA viruses, and high cost.

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Methods When a KT is ordered at our institution under the guidance of infectious diseases and microbiology laboratory leadership consultation, a blood sample (approximately 5 mL) is collected during routine care in EDTA vacutainer plasma preparation tubes. Samples are processed and shipped overnight to KariusDx. KariusDx performs cfDNA extraction upon receiving the samples, and next-generation sequencing libraries are prepared and performed as previously described. The results are available once ready in the KariusDx portal, and clinical microbiology representatives routinely log in to the system, download the results, and upload them to our electronic medical records.

We performed a retrospective review of all KT performed for UC San Diego patients from July 2017 to April 2024. We reviewed the patient’s medical records to determine if KT had identified a pathogen and changed patient care. Basic demographics, turnaround time (defined as the time from the specimen being received by the central processing laboratory to the result uploaded to the EMR), test results, reason for testing, and patient outcome were collected to assess the clinical utility of KT in the adult population.

For each case, we implemented criteria (Table 1) to determine KT’s clinical utility. Clinical utility was calculated by number-needed-to-test (NNT). This review was determined

Table 1.

Criteria

Description

Positive

Faster/Only diagnosis; Clinicians clearly acted on result

No Impact

Either diagnosed existing infection or did not modify treatment

Neutral

Help ruling out infectious causes with modification to the treatment (e.g., discontinuation of empiric coverage) or to strengthen the existing diagnosis (somewhat subjective decision)

to be IRB exempt from the UCSD Health Aligning and Coordinating Quality Improvement, Research, and Evaluation (ACQUIRE) Committee.

Results A total of 88 KTs from 88 unique patients were included in the analysis.

The median age of patients included in this cohort was 58 years old (SD 17.5, from 18 to 88 years old; 1st quartile: 40 years old, 3rd quartile: 68 years old), 36 (40.9%) tests were from female patients, and about half of the patients were white (Table 2). Of the 88 tests, 49 (55.7%) identified at least one pathogen. The median hospitalized days from admission to test ordering were 8.5 days. The median test turnaround time was three days (1st quartile: 2 days, 3rd quartile: 5 days).

In evaluating indication for testing, 22 (25%) tests were obtained for prolonged fever/sepsis of unknown origin, 22 (25%) with culture-negative infective endocarditis signs or symptoms, 10 (11.4%) for lung pathology including nodules, organizing pneumonia/pneumonitis, pleural effusion, cavitary lesion, or acute respiratory distress syndrome, 19 (21.6%) for central nervous system pathology including clinical meningoencephalitis, brain abscess/lesion, vasculitis, mycotic aneurysm, or endophthalmitis, 6 (6.8%) for osteomyelitis/discitis/ epidural abscess, 6 (6.8%)

Table 2. Demographic Characteristics Age (years) 58 ± 17.5 Sex (N) Male

61

Female

36

MTF

1

Total

88

Race/Ethnicity (%) White

47

Hispanic

30

African American

6

Asian

11

Other

6

for vascular/graft infection, and 2 (2.3%) for culture-negative septic joint (Table 3).

Among those with a positive clinical impact (N = 11), for the 8 cases KT was the only method to establish diagnosis; 3 were faster than conventional microbiology testing. A complete list of organisms identified on KT led to positive clinical impacts in brief clinical scenarios as shown in Table 4. Among clinical syndromes, the vascular or graft infections category showed promising results (4 out of 6 cases). Among 56 cases with no clinical effect, 50% were negative, which means no cell-free DNA of any microorganisms in the KariusDx database was detected in statistically significant amounts. Twenty-one cases were deemed as neutral clinical impact. The number needed to treat was 6.1; if all neutral results were considered positive impact, then 2.75.

Discussion Diagnosing infectious diseases remains challenging and often impossible without an invasive diagnostic procedure, resulting in less effective empiric treatment, prolonged hospital stays, and complications from hospitalization and invasive procedures. In this single tertiary academic center retrospective study, we performed the retrospective clinical utilization analysis of KT. A few studies have investigated KT’s performance characteristics and clinical utility on serum samples among the general patient population. The clinical impact of KT varies

Table 3. Indication of Testing Total (N)

Yes

Maybe

No

Fever, Sepsis NOS

22

2

10

10

Culture-Negative Infective Endocarditis

22

1

5

16

OM/Discitis/Epidural Abscess

6

0

1

5

Lung Pathology (Nodules, Organizing, ARDS, Pleural Effusion, Cavitary lesion)

10

1

3

6

Meningoencephalitis

10

1

3

6

Brain Abscess/Lesion

5

0

1

4

Endophthalmitis

1

1

0

0

CNS Vasculitis/Mycotic Aneurysm

4

1

1

2

Vascular/Graft Infection

6

4

0

2

Culture-Negative Septic Joint

2

0

0

2

SANDIEGOPHYSICIAN.ORG

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INFEC TIOUS DISE A SES

significantly, ranging from 7% to 56% depending on the patient population and/or clinical syndrome studied7. For example, in a single-center retrospective study, KT was found to be compatible with the definitive diagnosis in 65% of cases and was assessed as having a positive impact in 43% (34) of cases8. KT was associated with more excellent clinical utility in the setting of solid organ transplant recipients and in the setting of sepsis. In another single-center retrospective review, KT was assessed among immunocompromised patients, including those with B-cell and T-cell deficits. 58% of tests in this cohort identified at least one organism, and a positive test resulted in a modification to therapy in 14 of 21 patients9.

Recently, another single-center study showed approximately 46% of tests yielded a clinically significant pathogen10. On the contrary, the positive clinical impact rate in another multicenter study was only 7.3%, while most cases (86.6%) were determined to have no clinical impact11. Another study using the standardized criteria from this study assessed 80 patients without predefined clinical syndromes and found the rate of positive clinical impact to be 43%, with a considerable number of cases (55%) having no clinical impact12.

Our study implemented criteria developed and validated by two separate infectious disease specialists (SJ and AK), with an independent review process. We applied strict rules when defining the cases with positive impact, which led to a 12.5% positive rate (11 out of 88 cases). Defining cases with neutral impact was the weakest point of this chart review; it could be provider-dependent, subject, and grey zone. For example, discontinuing empiric coverage after the negative result, excluding other causes of treatment failure or clinical worsening, fell into this category. In some cases, KT was ordered with other conventional microbiology diagnostic testing, yet because of the test turnaround time, KT resulted later than traditional testing.

In conclusion, physicians should be aware of the various NGS testing options available and their strengths and limitations. In our review, KT has fair NNT, and negative test results may still be meaningful. If the cost of testing could be further reduced, it could effectively supplement or even replace current testing. Meanwhile, since this test is not FDA-approved and results in significant healthcare costs, including out-of-pocket burden to the patients, we suggest KT should only be considered with infectious disease specialist consultation.

Funding and Potential Conflict of Interests This work was supported by the National Institute of Health grant 5T32AI007036-43 (to SJ). The authors received no financial support for the research, authorship, and/or publication.

The authors have no conflict of interest with KariusDx.

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Table 4. A complete list of clinical scenarios and organisms identified on KT led to positive clinical impacts Aspergillus fumigatus in Endophthalmitis Herpes Simplex Virus-1 Encephalitis Pseudomonas Infection in Organizing Pneumonia E. coli in Culture-Negative Endocarditis Coagulase-Negative Staphylococci in Aortic Graft Infection Fusobacterium in Aortic Graft Infection Rothia dentocariosa in Iliac Pseudoaneurysm Stenotrophomonas in Aorto-Bifemoral Bypass Graft Infection Rhizomucor pusillus, Disseminated in Acute Myeloid Leukemia Patient Scedosporium boydii in PICA Mycotic Aneurysm, in Liver Transplanted Cytomegalovirus Viremia in Shock, Liver Transplant Candidate

Dr. Jung is a clinical fellow

microbiology laboratory

in the research track at

at UC San Diego, and

the Division of Infectious

co-director of the

Diseases and Global Public

microbiology block for

Health at UC San Diego

UCSD Schools of Medicine

School of Medicine. Before

and Pharmacy.

joining UCSD, he received

Dr. Abeles is an

medical training in the

infectious diseases

New York Medical College

physician and medical

— Metropolitan Program.

program director of

With his prior experiences

Antimicrobial Stewardship

in the MERS epidemic and

at UC San Diego Health.

the COVID-19 pandemic, he

Dr. Torriani is a

became a huge advocate of

professor of clinical

antimicrobial resistance

medicine in the

research as a consequence

Department of Medicine,

of novel pathogens.

Division of Infectious

Dr. Kline is an

Diseases and Global Health

assistant professor

at UC San Diego. Her

of clinical pathology,

current interests are in

associate director of the

implementation science

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

aimed at improving and

10.

sustaining high quality and safety in healthcare

11.

in cost-conscious and reproducible ways, as well as to shape and implement meaningful public health

12.

healthcare policies at the national and international levels. Dr. Torriani serves as the program director

13.

of UC San Diego Health’s Infection Prevention and Clinical Epidemiology and TB Control, as the chair of

14.

the SD Medical Society’s GERM Commission, and chairs the Infectious Diseases Society of America’s Practice and Quality Committee.

15.

Microbiology by numbers. (2011). Nature Reviews Microbiology, 9(9), 628–628. https://doi.org/10.1038/ nrmicro2644 L, S., & K, K. (2023). National Hospital Ambulatory Medical Care Survey: 2019 National Summary Tables. https:// doi.org/10.15620/cdc:123251 Gu, W., Miller, S., & Chiu, C. Y. (2019). Clinical metagenomic next-generation sequencing for pathogen detection. Annual Review of Pathology: Mechanisms of Disease, 14(1), 319–338. https://doi.org/10.1146/annurevpathmechdis-012418-012751 Rodino, K. G., & Simner, P. J. (2024). Status check: Next-generation sequencing for infectious-disease diagnostics. Journal of Clinical Investigation, 134(4). https://doi.org/10.1172/jci178003 Fenollar, F., & Raoult, D. (2007). Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria. International Journal of Antimicrobial Agents, 30, 7–15. https://doi.org/10.1016/j.ijantimicag.2007.06.024 Mancini, N., Carletti, S., Ghidoli, N., Cichero, P., Burioni, R., & Clementi, M. (2010). The era of molecular and other non-culture-based methods in diagnosis of sepsis. Clinical Microbiology Reviews, 23(1), 235–251. https:// doi.org/10.1128/cmr.00043-09 Fishman, J. A. (2007). Infection in solid-organ transplant recipients. New England Journal of Medicine, 357(25), 2601–2614. https://doi.org/10.1056/nejmra064928 Clinical data. Karius. (n.d.). https://kariusdx.com/clinical-evidence/clinical-data. Assessed on 08/19/2024.

Blauwkamp, T. A., Thair, S., Rosen, M. J., Blair, L., Lindner, M. S., Vilfan, I. D., Kawli, T., Christians, F. C., Venkatasubrahmanyam, S., Wall, G. D., Cheung, A., Rogers, Z. N., Meshulam-Simon, G., Huijse, L., Balakrishnan, S., Quinn, J. V., Hollemon, D., Hong, D. K., Vaughn, M. L., … Yang, S. (2019). Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease. Nature Microbiology, 4(4), 663–674. https://doi. org/10.1038/s41564-018-0349-6 Morales, M. (2021). The next big thing? next-generation sequencing of microbial cell-free DNA using the Karius Test. Clinical Microbiology Newsletter, 43(9), 69– 79. https://doi.org/10.1016/j.clinmicnews.2021.04.003 Noe, M. M., Shishido, A. A., Saharia, K., & Luethy, P. (2021). 661. clinical utility and impact of the metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decision: A SingleCenter Retrospective Study. Open Forum Infectious Diseases, 8(Supplement_1). https://doi.org/10.1093/ofid/ ofab466.858 Vissichelli, N. C., Morales, M. M., Kolipakkam, B., Bryson, A. L., Nixon, D., Sabo, R. T., & Toor, A. A. (2021).

669. metagenomic plasma microbial cell free DNA-sequencing assists in diagnosis of infections and critical antimicrobial changes in immunocompromised hosts.

Open Forum Infectious Diseases, 8(Supplement_1). https://doi.org/10.1093/ofid/ofab466.866 Aiden-Croix Thompson, R., Donnelley, M., Thompson III, G., Fan, S., Wilson, M., Trigg, K., Cohen, S., & Desai, A. (2024). Utility of Microbial Cell Free DNA NextGeneration Sequencing for Diagnosis and Management of Infectious Diseases: A Retrospective Cohort Study. https:// doi.org/10.2139/ssrn.4689645 Hogan, C. A., Yang, S., Garner, O. B., Green, D. A., Gomez, C. A., Dien Bard, J., Pinsky, B. A., & Banaei, N. (2020). Clinical impact of metagenomic nextgeneration sequencing of plasma cell-free DNA for the diagnosis of infectious diseases: A multicenter retrospective cohort study. Clinical Infectious Diseases, 72(2), 239–245. https://doi.org/10.1093/cid/ciaa035 Shishido, A. A., Noe, M., Saharia, K., & Luethy, P. (2022).

Clinical impact of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decisions: A single-center retrospective study. BMC Infectious Diseases, 22(1). https://doi. org/10.1186/s12879-022-07357-8

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Chagas Disease Is Now Reportable in San Diego County: What You Need to Know

By Meghan Villalobos, MPH, Audrey Kennar, MSPH, BSN, RN, Mark Beatty, MD, MPH, and Paula Stigler Granados, PhD, MS The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

CHAGAS DISEASE (CD), OR AMERICAN TRYPANOSOMIASIS,

is a vector-borne disease caused by the protozoan parasite Trypanosoma cruzi (T. cruzi). CD is a major cause of cardiovascular and gastrointestinal morbidity and mortality in continental Latin America. In the United States, most people living with CD were infected while residing in CD-endemic countries. The Center of Excellence for Chagas Disease has estimated that California residents have the highest number (70,000–100,000) of CD infections in the United States.1,2,3 CD is currently a reportable disease in eight U.S. states (Texas, Arkansas, Tennessee, Arizona, Louisiana, Mississippi, Utah, and Washington) and was previously reportable in Massachusetts. Because a considerable proportion of San Diego residents were suspected to be at risk for CD, it was made reportable in San Diego County on April 10, 2024; CD is also reportable in Los Angeles County.‡,4 CD is transmitted to humans and mammals by the triatomine insect, commonly known as the kissing bug.6,7 Triatomines are approximately a half-inch to 1 and a quarter inches in length, have a long, cone-shaped head with a dark brown or black body, and

are active primarily at night.

Triatomines become infected with the T. cruzi parasite by taking a blood meal from an infected mammal or person.

The transmission of T. cruzi is not caused by the bite of the triatomine bug itself.

Instead, the parasite is found in the feces of infected triatomines, and transmission occurs when contaminated feces comes into contact with broken skin or mucous membranes or is ingested orally. Triatomine species that feed and defecate in the same location are the most efficient vectors. Eleven triatomine species are known in the United States, and three of those species can be found throughout most of California in natural areas,

Reported triatomine distribution in the United States. Image by CDC.5

including rural foothills and mountainous areas. 8,9 The Triatoma protracta species is the most common triatomine species in California. This triatomine is considered an inefficient vector because it tends to defecate and bite in separate locations, decreasing the likelihood of local transmission.6,10,11 Although infection most commonly occurs when T. cruzi in triatomine feces contaminates a bite wound or the eye, other modes of transmission include congenital transmission (mother to fetus), blood transfusions (i.e., contaminated blood products), organ transplantation (i.e., an organ transplanted from an infected donor), consumption of uncooked food (i.e., food contaminated with T. cruzi-infected feces from triatomines), and accidental laboratory exposure.8 Clinical manifestations8 CD has both acute and chronic phases. Most acute infections are asymptomatic.

If left untreated, CD will progress to chronic disease.

Triatoma protracta.

Image by CDC.8

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Acute CD Acute CD occurs in the first eight to 10 weeks after exposure and subsequent infection. This initial phase

cruzi. Congenital CD can be characterized by low birth weight, prematurity, hepatosplenomegaly, anemia, thrombocytopenia, and meningoencephalitis; however, most infants are asymptomatic or have mild symptoms. Treatment is recommended for all patients with congenital CD; estimated cure rates are >90% if the baby is treated during the first year of life.12

Romaña’s sign. Image by WHO/TDR8 can be asymptomatic or can cause mild, self-limited symptoms. Reported symptoms include the following: • Swelling at the bite site • Fever • Fatigue • Rash • Body aches • Eyelid swelling • Headache • Loss of appetite • Nausea, diarrhea, or vomiting • Swollen lymph nodes • Enlargement of liver or spleen Romaña’s sign, swelling of the eyelid, can be an indication of acute CD. The swelling is caused when the parasite enters the body through the conjunctiva and multiplies locally, causing a firm swelling that persists for weeks. Romaña’s sign can be associated with ipsilateral regional lymphadenopathy.

Chronic CD CD is a lifelong disease if left untreated, but curable if treatment is initiated soon after infection. The chronic phase has two forms, chronic indeterminate (without symptoms) and chronic determinant (with symptoms). 7,8 Most chronically infected people will remain asymptomatic throughout their lifespan, but an estimated 20–30% of chronically

infected persons progress to develop severe and sometimes life-threatening clinical manifestations years to decades after acute infection. Clinical manifestations of chronic Chagas disease are most often cardiac but can also be gastrointestinal, including: Cardiac complications: • Irregular heartbeat • Heart failure • Sudden cardiac arrest Gastrointestinal complications: • Enlarged esophagus or colon • Difficulty eating or defecating • Chronic and recurrent abdominal pain These complications can result in the need for a cardiac transplant. Immunosuppressive medications required after a transplant can lead to reactivation of CD, causing further complications. Chronically infected patients are also at risk for reactivation due to HIV infection and low CD4 counts or immunomodulatory therapy for various autoimmune conditions.

Congenital CD The Centers for Disease Control and Prevention (CDC) estimates 1–5% (63–315) of infants born annually in the United States to mothers with CD are infected with T.

CD Diagnosis13 Acute CD can be diagnosed by visualization of T. cruzi parasites in blood through light microscopy (e.g. thick and thin smears, Giemsa-stained blood smears, wet mount examination). Whole blood samples can be tested for T. cruzi DNA by polymerase chain reaction. After identification of T. cruzi parasites through microscopic examination, healthcare providers should consult with the County of San Diego (CoSD) Epidemiology Unit. This review will determine if submission to CDC for confirmatory testing is indicated.

Chronic CD can be diagnosed based on serologic testing (e.g., enzyme immunoassay (EIA) detecting IgG antibodies to T. cruzi) and can be requested and performed using a commercial diagnostic laboratory, including ARUP, Quest Diagnostics, and Mayo Labs. After identification of T. cruzi antibodies, healthcare providers should consult with the CoSD Epidemiology Unit to determine if submission to CDC for confirmatory testing is indicated, because one test is not sensitive or specific enough for diagnosing chronic CD. CDC offers confirmatory Chagas disease serology. Healthcare personnel working with specimens from patients suspected of having CD must use standard precautions. Trypomastigotes, the infectious form of T. cruzi, are highly infectious, and certain strains of the parasite are more virulent than others.14 CD Treatment13 The American Academy of Pediatrics supports treatment of CD in pediatric patients. Treatment is indicated for children aged <18 years and all patients with acute or reactivated CD.15 Congenital infections are considered acute disease. For adults aged ≤50 years, treatment is strongly recommended for patients with chronic infection who do not already have advanced cardiomyopathy. For adults aged >50 years, the decision to treat patients with chronic infection using antiparasitic drugs should be individualized.16 Benznidazole and nifurtimox are the two FDA-approved antiparasitic medications recommended for treatment of CD in children and adults. Benznidazole is FDA-approved for CD in patients 2–12 years of age. Use of benznidazole for patients outside the approved age range is based on clinical discretion of the patient’s treating physician under practice of medicine.

Lampit® (nifurtimox) is FDA-approved for CD treatment in patients from birth to <18 years (weighing at least 2.5 kg). Use of nifurtimox to treat a patient outside this age range is based on clinical discretion of the patient’s treating physician under practice of medicine.17,18 SANDIEGOPHYSICIAN.ORG

7

INFEC TIOUS DISE A SES CD in San Diego County San Diego County is located on the United States-Mexico border, the busiest land border in the Western Hemisphere, where people from CD-endemic regions often enter the United States.19 To assess frequency of CD infections in San Diego County, CoSD Health and Human Services Agency (HHSA) conducted retrospective case-finding at multiple sentinel sites. This activity was reviewed

by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy.§ In addition to voluntary case reporting, CoSD HHSA identified any positive CD test result during 2018–2023 from patient chart review using International Classification of Diseases, Tenth Revision codes B57–B57.5 for acute and chronic CD and routine bloodborne pathogen screening results from a blood bank and cardiac transplant center. Half of 98 identified patients had confirmed (9%), probable (14%), or suspect (28%) CD classification status.‽ Most (62%) of the confirmed, probable, or suspect patients were identified through blood bank screening, which had 10.3 times more cases than those identified by voluntary reporting alone (6%). Among patients with a confirmed, probable, or suspect CD diagnosis, 30% self-identified as Hispanic or Latino, and ethnicity was unknown in 34%.

CoSD Response Through CD surveillance and case investigation, CoSD is monitoring for local transmission and epidemiologic trends.

CoSD investigates CD reports and inquiries using a standard case report form to capture disease-specific exposures, clinical criteria, and determine case classification. Currently, no formal Council of State and Territorial Epidemiologists (CSTE) case definition for CD is available, and each jurisdiction where CD is reportable has established its own case definition used for disease surveillance. During the 2024 CSTE Conference, a nationwide CSTE case definition for CD was approved and will be implemented in January 2025.

In San Diego County, healthcare providers, laboratories, and blood banks are now required to report laboratory evidence of CD to CoSD within seven business days. Providers should screen for CD in patients with a known exposure (e.g., lived ≥6 months in Mexico, Central or South America, who were born to a mother who lived ≥6 months in Mexico, Central or South America, who have a family member with CD, or who had known contact with triatomines in the United States or Latin America) to facilitate early intervention.4,20 Prenatal screening is an effective way to identify infants who require further follow up and potential treatment including antiparasitic or supportive treatment.4,21 Southern California Chagas Disease Collaborative After CD became reportable in CoSD, the Southern California Chagas Disease Collaborative was created in collaboration with San Diego State University. The collaborative seeks to facilitate information sharing and provide answers regarding CD screening, diagnostics, and reporting among partners and providers throughout Southern California. The collaborative hopes to enhance screening and surveillance efforts, increase CD aware8

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ness and understanding, develop partnerships, create resource materials for local providers, and establish an annual report summarizing collaborative activities. Through these efforts, the Southern California Chagas Disease Collaborative plans to ensure that healthcare providers are well equipped to address challenges posed by CD, ultimately contributing to better public health outcomes in the region. ‡ All CD-positive laboratory tests are required to be reported to CoSD within seven days after receipt of the positive result by completing the Confidential Morbidity Report and submitting to the County Epidemiology Unit. ‽ The case definition CoSD used for CD case classification of the data collected: Confirmed case has positive confirmatory laboratory testing through CDC; probable case has supportive laboratory evidence of infection with evidence of epidemiologic risk factors or clinically compatible illness; and suspect case has supportive laboratory evidence of infection without evidence of clinically compatible symptoms. § See e.g., 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. §241(d); 5 U.S.C. §552a; 44 U.S.C. §3501 et seq.

Meghan Villalobos is an epidemiologist II at the County of San Diego Health and Human Services Agency. Her work supports the One Health Epidemiology Program in the Epidemiology and Immunization Services Branch. She investigates cases and outbreaks of communicable and zoonotic disease and is the branch’s subject matter expert on Chagas disease.

Audrey Kennar is a CDC epidemic intelligence service officer assigned to the County of San Diego Health and Human Services Agency Epidemiology and Immunization Services branch and CDC’s Division of Global Migration Health Southern Border Health and Migration branch. She enjoys bringing her nursing background into her work as an epidemiologist.

Dr. Beatty served eight years in the U.S. Public Health Service with assignments to the Navajo Nation and Centers for Disease Control and Prevention. Dr. Beatty joined the Epidemiology and Immunization Services at the County of San Diego Health and Human Services in 2020 and currently is the assistant medical director.

Paula Stigler Granados is an associate professor and division head for Environmental Health at the School of Public Health.

Her primary research focus is on Chagas disease, where she leads several projects, including a CDC-funded initiative to raise awareness among U.S. healthcare providers and a Department of Defense grant for surveillance of Chagas disease in military communities along the U.S.-Mexico border. Dr. Granados is a subject matter expert on Chagas disease and is leading the efforts to develop the Southern CA Chagas Disease Collaborative.

References

11.

1.

Irish A, Whitman JD, Clark EH, et al. Updated Estimates and Mapping for Prevalence of Chagas Disease among Adults, United States. Emerging Infectious Diseases.

2022;28(7):1313-1320. doi:10.3201/eid2807.212221.

2. Center of Excellence for Chagas Disease. Chagas Disease in California. Chagasus. org. n.d. Accessed June 17, 2024. https://chagasus.org/chagas-disease-in-california/ 3. Manne-Goehler J, Umeh CA, Montgomery SP, Wirtz VJ. Estimating the burden of Chagas disease in the United States. PLoS Neglected Tropical Diseases. 2016;10(11). https://doi.org/10.1371/journal.pntd.0005033 4. County of San Diego. Chagas Disease (American trypanosomiasis). Sandiegocounty. gov. Updated May 8, 2024. Accessed June 17, 2024. https://www.sandiegocounty. gov/content/sdc/hhsa/programs/phs/community_epidemiology/dc/chagasdisease. html#:~:text=Chagas%20disease%20is%20a%20reportable%20disease%20in%20 8,reportable%20in%20San%20Diego%20County%20as%20of%202024.

5. Centers for Disease Control and Prevention. How Chagas Disease Spreads. CDC.gov.

Updated February 26, 2021. Accessed July 25, 2024. https://www.cdc.gov/chagas/ spreads/index.html 6. California Department of Public Health Division of Communicable Disease Control.

Conenose Bugs in California: Information for Vector Control Agencies and Health Professionals. CDPH.ca.gov. Updated December 2019. Accessed September 13, 2023. https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/ ConenoseBugsinCalifornia.pdf.

7. Centers for Disease Control and Prevention. American trypanosomiasis. CDC.gov.

Updated June 16, 2021. Accessed June 17, 2024. https://www.cdc.gov/dpdx/trypanosomiasisamerican/index.html 8. Centers for Disease Control and Prevention. About chagas disease. CDC.gov. Updated February 23, 2024. Accessed June 17, 2024. https://www.cdc.gov/chagas/about/ index.html#cdc_disease_basics_causes_risk_spread-how-it-spreads 9. Dye-Braumuller, K. C., Lynn, M. K., & Nolan, M. S. (2021). History of indigenous Trypanosoma cruzi infection in humans, animals and triatomines in California, USA. Zoonoses and Public Health, 68(4), 299-308.

10. Colorado Department of Public Health & Environment. Chagas Disease and Kissing Bugs. Cdphe.colorado.gov. Published in 2023. Accessed September 15, 2023. https:// cdphe.colorado.gov/chagas.

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Centers for Disease Control and Prevention. Information on Species of Triatomine Bugs in the United States. CDC.gov. Updated February 24, 2024. Accessed July 10, 2024. https://www.cdc.gov/chagas/hcp/species/index.html Centers for Disease Control and Prevention. Clinical Considerations for Congenital Chagas Disease. CDC.gov. Updated June 12, 2024. Accessed June 18, 2024. https:// www.cdc.gov/chagas/hcp/considerations/index.html County of San Diego. Chagas Information for Healthcare Professionals. Sandiegocounty.gov. Updated July 17, 2024. Accessed July 25, 2024. https://www.sandiegocounty.gov/content/sdc/hhsa/programs/phs/community_epidemiology/dc/chagasdisease/chagashealthcareprofessionals.html Osorio L, Ríos I, Gutiérrez B, González J. Virulence factors of Trypanosoma cruzi: who is who? Microbes and Infection. 2012;14(15),1390-1402. https://doi.org/10.1016/j. micinf.2012.09.003 American Academy of Pediatrics. American Trypanosomiasis (Chagas Disease). Red Book: 2021–2024 Report of the Committee on Infectious Diseases (32nd Edition).

Published 2021. Accessed July 25, 2024. https://doi.org/10.1542/9781610025782-S3_149 Centers for Disease Control and Prevention. Clinical Care of Chagas Disease. CDC. gov. Updated February 2, 2024. Accessed August 27, 2024. https://www.cdc.gov/chagas/hcp/clinical-care/index.html#:~:text=Antiparasitic%20treatment%20is%20indicated%20for%20all%20cases%20of,infection%20who%20do%20not%20already%20 have%20advanced%20cardiomyopathy.

Centers for Disease Control and Prevention. Treatment of Chagas Disease. CDC.gov.

Updated February 9, 2024. Accessed June 25, 2024. https://www.cdc.gov/chagas/ treatment/index.html#:~:text=specialist%20if%20necessary.-,Treatment%20 options,symptoms%20and%20signs%20of%20infection.

Clark EH, Bern C. Chronic Chagas Disease in the US. JAMA. 2024;331(23):2037-2038. doi:10.1001/jama.2024.3717 General Services Administration. San Ysidro Land Port of Entry Fact Sheet. Gsa.gov.

Updated December 11, 2019. Accessed July 10, 2024. https://www.gsa.gov/system/files/ Overarching%20San%20Ysidro%20Fact%20Sheet%20-%20Dec%2011%202019.pdf Forsyth CJ, Manne-Goehler J, Bern C, et al. Recommendations for screening and diagnosis of Chagas disease in the United States. J Infect Dis. 2022;225(9),1601-1610. doi: 10.1093/infdis/jiab513.

Chancey RJ, Edwards MS, Montgomery SP. Congenital Chagas Disease. Pediatr Rev. 2023;44(4),213. doi: 10.1542/pir.2022-005857.

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County of San Diego One Health Epidemiology Program – Links Human and Animal Health

By Emily Trumbull, DVM, Sarah Stous, MPH, Julie Breher, DVM, MPVM, Catherine Blaser, MPH, RN, PHN, ACRN, CIC, Erik A. Berg, MD, Mark Beatty, MD, MPH, Jeffrey Johnson, MPH, and Seema Shah, MD, MPH EVERY DAY, OUR HEALTH IS AFFECTED BY THE AIR WE

breathe, the food we eat, the place we live, and the animals with which we interact. The concept that our health is connected to animal and environmental health is called “One Health.” It is estimated that over 75% of emerging infectious diseases come from animals, also called zoonoses. Therefore, examining animal population health can help us understand emerging diseases that can impact human health. Beyond zoonoses, both animals and people are dependent on a healthy environment. Air quality, water quality, weather patterns, and biodiversity of plants are all essential to make up healthy environments and ecosystems for all life to thrive.

The One Health concept is not new. The interconnectedness of the natural world of humans, animals, and environments are central to the traditional ecologic knowledge of indigenous communities dating back tens of thousands of years.1-2 The Greek philosopher Hippocrates acknowledged the health of people is dependent on the environment.3 Rudolf Virchow, a German physician and pathologist in the 19th century, coined the term “zoonosis” and stated, “Between animal and human medicine there are no dividing lines — nor should there be. The object is different, but the experience obtained constitutes the basis of all medicine.” Today, advances in medicine rely on the outcomes of laboratory animal studies to understand pathophysiology and extrapolate safe medical and surgical techniques for people.

The Health and Human Services Agency’s Public Health Services, at the County of San Diego, has acknowledged the need to integrate more animal health into their epidemiology and laboratory practices. The One Health Epidemiology Program (OHEP) was established in 2023 and is dedicated to surveillance, investigation, response, and prevention of zoonotic disease outbreaks and spillover events. This multidisciplinary team is comprised of epidemiologists, veterinarians, physicians, nurses, and laboratorians who support zoonotic disease surveillance and response efforts in the county. To ensure that this work is synergistic with other groups and agencies, OHEP also collaborates with local, state, and federal partners, including the California Department of Public Health (CDPH), on many topics including rabies regulations

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and prevention and Brucella canis case investigations. We collaborate with both the United States Department of Agriculture (USDA) and the California Department of Food and Agriculture (CDFA) on case investigations involving livestock and with the California Department of Fish and Wildlife (CDFW) on wildlife disease investigations.

Following a new program planning and prioritization phase, OHEP surveillance and investigation efforts have focused on identifying and confirming zoonotic transmission of reportable diseases between humans and animals within the county. The OHEP collects surveillance data on reported zoonotic diseases in humans and conducts analysis on a weekly basis to identify trends across multiple diseases. Data sharing from veterinary reference diagnostic laboratories and electronic reporting has expanded county data collection from local veterinarians, including animal shelters and wildlife rehabilitators. Furthermore, OHEP has conducted multiple field investigations and obtained animal samples for testing by the San Diego County Public Health Laboratory and affiliated laboratories for diseases such as rabies, brucellosis, avian chlamydiosis, leptospirosis, salmonellosis, Shiga-toxin-producing Escherichia coli, and Rocky Mountain spotted fever.

Notably, OHEP has developed multiple avenues for public outreach and education to become a local resource for animal health and zoonotic disease information. First, the team launched a website that includes educational resources, updates of local relevance, and public health messaging for the wider community of human and veterinary health professionals. Second, a newsletter was created for regional human and veterinary medical professionals to share updates with clinicians. Third, hybrid continuing education events for veterinarians were developed to increase knowledge and skills on a variety of public health topics, e.g. rabies, Rocky Mountain spotted fever, and other vector-borne diseases. Fourth, outreach activities have included briefing local healthcare professionals at the Epidemiology and Immunization Services Branch’s monthly Current Issues in Public Health Epidemiology meeting, providing information on regulations and zoonotic diseases for animal importation/rescue groups,

and coordinating in-person visits to veterinary hospitals, animal exhibits, and public fairs. Educational resources (like laminated infection prevention and biosecurity signage) have been provided to groups interested in exploring engagement opportunities with OHEP. As wildlife is essential to maintain healthy ecosystems enjoyed by both people and animals, OHEP is eager to partner with conservation groups to support wildlife health in San Diego County. Currently, OHEP is collaborating with the CDFW on building capacity for zoonotic disease investigations in wildlife, with the National Oceanographic and Atmospheric Association (NOAA) on expanding response and disease investigation in stranded, deceased marine mammals, and with the San Diego Natural History Museum to increase our knowledge of local bat ecology. OHEP continues to develop partnerships to pursue grant opportunities that support and expand the scope of work activities.

An example of a zoonotic disease event that has required increased preparedness and response from OHEP is the outbreak of highly pathogenic avian influenza (H5N1). In 2021, H5N1 emerged in wild birds in North America. Subsequent outbreaks have since occurred, affecting millions of poultry and resulting in changes in stability of the food supply of eggs across the country. H5N1 has continued to spill over to mammalian species, including a range of wildlife that have come in contact or eaten deceased birds affected by H5N1.

In 2024, an outbreak of H5N1 in dairy cattle occurred in the Midwestern United States from a spillover event from wild birds. H5N1 has now been identified as being able to move mammal-to-mammal through epidemiologic genomics studies and laboratory animal studies in mice, ferrets, and cows.

Subsequently, 14 people in the United States have become infected from direct contact with infected animals.

Although the risk to public health remains low, and no

human-to-human transmission has been documented, the Centers for Disease Control and Prevention (CDC) has identified an increased risk to those working closely with infected animals. Influenza A viruses also have pandemic potential, which makes prevention strategies necessary. OHEP works to optimize collaboration with high-risk personnel throughout the county who could come into contact with infected animals by meeting with these groups and providing education resources and guidance on H5N1, quarantine and disinfection practices, and recommended PPE supplies. We reviewed what to do if individuals become symptomatic within the incubation period for H5N1. Following the announcement from the CDC and CDPH, free personal protective equipment from the local stockpile has been offered and distributed to local farms, livestock and wildlife veterinarians, and animal control staff.

Educational materials and signage have been distributed to local veterinary and human medical professionals.

Post-exposure monitoring strategies of those who have come in contact with infected animals have been developed by the CDC and CDPH. In order to monitor those people exposed to a suspected infected animal, animal testing must be available in a timely and efficient manner. Working with the County’s local wildlife rehabilitation groups, a need was identified to increase animal testing capacity and speed for influenza A. OHEP has collaborated with entities in the government and private sectors to increase animal testing locally, so that we can monitor humans who have encountered potentially ill and infected animals. In 2022 and 2023, highly pathogenic avian influenza (H5N1) was detected in San Diego County in wild birds (2022 and 2023) and in poultry (2022).

We expect more local animal cases this fall during the migration of wild birds and have been working collaboratively with CDPH and local human and animal health professionals on preparedness efforts for any human exposures and/or cases.

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What Clinicians Need to Know about H5N14-11 • Although a seasonal flu vaccination will not directly protect against H5N1 infections, it is recommended to poultry and dairy workers by the CDC and CDPH Occupational Health Branch to keep workers healthy and decrease risk of co-infection with seasonal flu and H5N1.

• If a patient presents with respiratory illness with or without fever, and/or conjunctivitis: • Ask if the patient has been exposed to dairy cows, raw milk, poultry, wild birds, agricultural fairs, marine mammals, or humans infected with H5N1 within the past 10 days.

• Manage the patient outside for testing, if possible.

• Wear recommended PPE and follow standard contact and airborne precautions in hospital.

• Gloves, gown, N95 respirator or greater, goggles or face shield • Administer a flu test (preferably a RT-PCR).

• If positive for Influenza A, B, and if not typeable; report flu positive cases with exposures to dairy cows, raw milk, poultry, wild birds, agricultural fairs, or marine mammals within the past 10 days to the Epidemiology Unit at (619) 692-8499 or after hours (858) 565-5255.

• Positive flu tests should be forwarded to the Public Health Lab for confirmation.

• Consider antiviral treatment and antiviral prophylaxis for contacts of sick patients with confirmed or probable influenza A (H5N1).

• Specimen Collection Guidance12: • For patients who only have conjunctivitis, CDC recommends collecting both a conjunctival swab and nasopharyngeal swab in separate tubes of sterile viral transport media.

• For patients with both conjunctivitis AND respiratory symptoms, CDC recommends collection of three specimen into separate tubes with sterile viral transport media: • Conjunctival swab • Nasopharyngeal swab • Combined nasal swab and oropharyngeal swab The more we can share and learn from expertise across human and veterinary medicine, the more each sector can benefit. Many aspects of the government, research, and the private sectors have been siloed, and not addressing the areas where their work overlaps with others is detrimental to the efforts and success of each stakeholder. Using a One Health approach means sharing information and developing a holistic solution to complex issues. If you are interested in learning more or working with the OHEP team, please contact us at phs.ohep.hhsa@sdcounty.ca.gov.

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Dr. Trumbull joined the County of San Diego Epidemiology and Immunization Services Branch in 2023. She has worked with a range of species and is currently a practicing aquatics and wildlife veterinarian.

Dr. Breher joined the County of San Diego, Public Health Laboratory in 2023. Dr. Breher’s clinical background includes practicing small animal (dogs and cats) and food animal medicine.

Catherine Blaser has worked with the County of San Diego Health and Human Services Agency for 15 years in areas related to disaster medical and public health emergency preparedness, bioterrorism and medical countermeasures planning, and communicable disease epidemiology. Prior to that her nursing work included infectious disease clinical care and research, clinical education, and teaching for a local university.

Dr. Beatty served eight years in the US Public Health Service with assignments to the Navajo Nation and Centers for Disease Control and Prevention. Dr. Beatty joined the Epidemiology and Immunization Services at the County of San Diego Health and Human Services in 2020 and currently is the assistant medical director.

Dr. Berg joined the County of San Diego Epidemiology and Immunization Services Branch full-time in 2023 and is currently the interim medical director. He is a practicing emergency physician.

Sarah Stous joined the County of San Diego Epidemiology and Immunization Services Branch in 2017. Her work has included investigation of communicable diseases and outbreaks, data analysis, and response.

Jeffrey Johnson is branch chief of Epidemiology and Immunization Services. Jeffrey has nearly 30 years of public health experience working in the areas of disease reporting and surveillance, communicable disease control, health assessment, strategic planning, and emergency preparedness and response.

When not at work, Jeffrey can often be found experiencing remote wilderness interfaces between human and animals.

Dr. Shah joined the County of San Diego in 2021 as the medical director of Epidemiology and Immunization Services and is now serving as the interim deputy public health officer. Prior to the County, Dr. Shah served as a pediatric emergency medicine physician at Rady Children’s and UC San Diego, where she provided clinical care and led various roles including as medical director of the Emergency Department and interim chief of the Division of Emergency Medicine.

References 1.

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Pollowitz M, Allick C, Campbell KB, Ellison NL, Perez-Aguilar G, Vera M, Ramirez V, Nadal D, Meisner J. One Health, many perspectives: Exploring Indigenous and Western epistemologies. CABI One Health. 2024 Jul 1;3(1).

Riley T, Anderson NE, Lovett R, Meredith A, Cumming B, Thandrayen J. One Health in Indigenous Communities: A Critical Review of the Evidence. Int J Environ Res Public Health. 2021 Oct 28;18(21):11303. doi: 10.3390/ijerph182111303. PMID: 34769820; PMCID: PMC8583238.

Roncada, P.; Modesti, A.; Timperio, A.M.; Bini, L.; Castagnola, M.; Fasano, M.; Urbani, A. One Medicine–One Health–one biology and many proteins: Proteomics on the verge of the One Health approach. Mol. Biosyst. 2014, 10, 1226–1227.

Updates on Highly Pathogenic Avian Influenza (HPAI) [Internet]. [place unknown; published by United States Food and Drug Administration]; 2024 August 22. Available from: https://www.fda.gov/food/alerts-advisories-safety-information/updates-highly-pathogenic-avian-influenzahpai#new Prevention and Antiviral Treatment of Avian Influenza A Viruses in People [Internet]. [Place unknown; published by Centers for Disease Control and Prevention]; 2024 July 19. Available from: https://www.cdc. gov/bird-flu/prevention/index.html#:~:text=While%20getting%20a%20 seasonal%20flu,weeks%20before%20their%20potential%20exposure.

Detections of Highly Pathogenic Avian Influenza (HPAI) in Livestock [Internet]. [place unknown; published by: United States Department of Agriculture, Animal and Plant Health Inspection Service]; Available from: https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/livestock/h5n1-beef-safety-studies H5N1 and Safety of U.S. Meat Supply [Internet]. [place unknown; published by United States Department of Agriculture, Animal and Plant Health Inspection Service]; Available from: https://www.aphis.usda.gov/ livestock-poultry-disease/avian/avian-influenza/hpai-detections/livestock/testing-and-science/meat-safety

PLACE YOUR AD HERE Contact Jennifer Rohr 858.437.3476 Jennifer.Rohr@SDCMS.org

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Guan L, Eisfeld AJ, Pattinson D, Gu C, Biswas A, Maemura T, Trifkovic S, Babujee L, Presler Jr R, Dahn R, Halfmann PJ. Cow’s Milk Containing Avian Influenza A (H5N1) Virus—Heat Inactivation and Infectivity in Mice. New England Journal of Medicine. 2024 May 24. Interim Guidance for Infection Control Within Healthcare Settings When Caring for Confirmed Cases, Probable Cases, and Cases Under Investigation for Infection with Novel Influenza A Viruses Associated with Severe Disease [Internet]. [place unknown; published by Centers for Disease Control and Prevention]; 2024 March 9. Available from: https://www.cdc.gov/bird-flu/ hcp/novel-flu-infection-control/index.html Health Advisory; Influenza Testing Guidance: Enhanced Surveillance During the Summer Months [Internet]. [Place San Diego County; Published by County of San Diego, Public Health Services]. 2024 June 18.

Available from: https://www.sandiegocounty.gov/content/dam/sdc/hhsa/ programs/phs/cahan/communications_documents/6-18-2024.pdf Interim Guidance on the Use of Antiviral Medications for Treatment of Human Infections with Novel Influenza A Viruses Associated with Severe Human Disease [Internet]. [Place unknown; Published by Centers for Disease Control and Prevention]. 2024 May 24. Available From:https://www. cdc.gov/bird-flu/hcp/novel-av-treatment-guidance/index.html Interim Guidance on Influenza Antiviral Chemoprophylaxis of Persons Exposed to Birds with Avian Influenza A Viruses Associated with Severe Human Disease or with the Potential to Cause Severe Human Disease [Internet]. [Place unknown; Published by Centers for Disease Control and Prevention]. 2022 March 24. Available from: https://www.cdc.gov/bird-flu/ hcp/guidance-exposed-persons/index.html Conjunctival Swab Specimen Collection for Detection of Avian Influenza A (H5) Viruses [Internet]. [Place unknown; Published by Centers for Disease Control and Prevention]. Available from: https://www.cdc.gov/birdflu/media/pdfs/2024/07/conjunctival-swab-collection-avian-influenza.pdf

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The Art of Managing GramNegative Resistance: Key Updates on Practice-Changing Guidance

By Victor Chen, PharmD, Christopher Baladad, PharmD, Helen Berhane, PharmD, Nina Haste, PharmD, PhD, Nancy Law, DO, and Shira Abeles, MD ANTIMICROBIAL-RESISTANT, GRAM-NEGATIVE INFECTIONS

are significant contributors to morbidity and mortality, posing substantial management challenges. The latest Infectious Diseases Society of America (IDSA) Antimicrobial Resistance (AMR) Guidance (version 4.0) introduces practice-changing recommendations for managing Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia infections.1 Below, we summarize the key updates and their underlying rationale.

Select Updates on Recommendations for Managing Resistant Gram-Negative Infections Pseudomonas aeruginosa - Gentamicin is no longer considered effective therapy against Pseudomonas aeruginosa - High-dose, extended-infusion β-lactam therapy is recommended in treating Pseudomonas aeruginosa infections.

- Once-daily tobramycin or amikacin is a treatment consideration for pyelonephritis or complicated urinary tract infections (UTI) - Newer β-lactam agents active against Pseudomonas aeruginosa (i.e. ceftolozane-tazobactam, ceftazidimeavibactam, imipenem-cilastatin-relebactam, cefiderocol) retain high activity against carbapenem-resistant Psuedomonas aeruginosa. Obtain antimicrobial susceptibility testing (AST) for these agents to guide treatment decisions.

Carbapenem-resistant Acinetobacter baumannii (CRAB) - Sulbactam-durlobactam is recommended as one of the first-line choices in combination with a carbapenem against multi-drug resistant Acinetobacter baumannii infections.

- Institutions that do not have sulbactam-durlobactam on formulary may use high-dose, extended-infusion ampicillin-sulbactam in combination with another antibiotic active against Acinetobacter baumannii.

Stenotrophomonas maltophilia - Ceftazidime is no longer considered effective therapy for Stenotrophomonas maltophilia.

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AmpC-producing Enterobacterales - The “SPACE/SPICE” acronym for organisms harboring AmpC β-lactamase overestimates the presence of this gene among bacteria genuses.

- “HECK-YES” (Hafnia alvei, Enterobacter cloacae complex, Citrobacter freundii Klebsiella aerogenes, Yersinia enterocolitica) organisms are more likely to harbor these ampC genes.

- Cefepime is considered a robust therapy for AmpC producing Enterobacterales.

Pseudomonas aeruginosa Pseudomonas is a notoriously common and resistant organism to treat. Common β-lactam resistance mechanisms for Pseudomonas aeruginosa include outer membrane porin mutations, upregulations of efflux pumps, β-lactamases, penicillin-binding protein mutations, and in rare cases, carbapenemases.2 Management of difficult-to-treat (DTR) Pseudomonas aeruginosa can be challenging. The new IDSA AMR 4.0 guidance takes a deeper dive into aminoglycoside utilization and describes the drastic shift in susceptibility interpretations of microbiology laboratory data.

Aminoglycosides are utilized as adjunctive agents in difficult-to-treat gram-negative infections due to rapid, concentration-dependent antibacterial activity. Use is limited by their nephrotoxic and ototoxic effects. Recent literature evaluations suggest that despite optimized dosing regimens that reduce or minimize toxicities, the efficacy and utility of aminoglycosides may be limited and, in some cases, no longer recommended. A recent re-evaluation of breakpoints led the Clinical Laboratory Standards Institute (CLSI) to update breakpoints for aminoglycosides use in Pseudomonas aeruginosa and Enterobacterales.3 For Psuedomonas aeruginosa, notably, gentamicin breakpoints have been removed and gentamicin is no longer considered a treatment option.

Clinicians should be aware of these antimicrobial updates, especially if gentamicin is no longer listed on a susceptibility panel and collaborate with their laboratory partners to ensure they are using the updated breakpoints. If the Pseudomonas

isolate is resistant to carbapenems, but susceptible to a traditional non-carbapenem β-lactam (e.g., cefepime), the guidance’s preferred approach is to administer the non-carbapenem agent as high-dose extended-infusion therapy (see the below table). The antibiotic stewardship implications of prolonging the infusion of β-lactams are significant, as this approach optimizes the drug’s pharmacodynamic properties.4-6 Institutions that do not currently employ prolonged infusions of β-lactam antibiotics may need to consider adopting these strategies to enhance treatment efficacy. Physicians should collaborate closely with their pharmacists to assess the feasibility of implementing these practices in their clinical settings.

New agents ceftolozane-tazobactam (C/T), ceftazidime-

avibactam (CZA), and cefiderocol all appear effective against P. aeruginosa. Cross resistance may occur with ceftazidimeavibactam and ceftolozane-tazobactam due to structural similarities, while other antimicrobial therapies lack resistance emergence data.7,8 Imipenem-cilastatin-relebactam may retain activity against patients with prior exposure to C/T or CZA for DTR Pseudomonas aeruginosa; however, susceptibilities should be confirmed. Finally, cefiderocol has been shown to have increased all-cause mortality compared to the best available therapy for DTR Pseudomonas aeruginosa.9 Overall, patient-specific factors, resistance history, and formulary restrictions are important considerations for choosing appropriate therapy.

Select suggested antibiotic dosing and 2024 CLSI breakpoints for Pseudomonas aeruginosa adapted from IDSA AMR Guidance (version 4.0) Antibiotic

MIC Breakpoint for Susceptibility (µg/mL)

Recommended Dosing Uncomplicated cystitis: 15 mg/kg IV as a single dose

Amikacin

≤16

Cefepime

≤8

Table 3. Indication of Testing

Pyelonephritis or complicated UTI: 15 mg/kg IV once; subsequent dosing varies by PK evaluation Uncomplicated cystitis: 1 gram IV every 8 hours, infused over 30 minutes All other infections: 2 grams IV every 8 hours, infused over 3 hours

Cefiderocol

≤4

2 grams IV every 8 hours, infused over 3 hours CrCL ≥120 mL/min: 2 grams IV every 6 hours, infused over 3 hours

Ceftazidime

≤8

2 grams IV every 8 hours, infused over 3 hours

Ceftazidime-avibactam

≤8/4

2.5 grams IV every 8 hours, infused over 3 hours

Ceftolozane-tazobactam

≤4/4

3 grams IV every 8 hours, infused over 3 hours

Imipenem-relebactam

<2/4

1.25 grams IV every 6 hours, infused over 30 minutes Uncomplicated cystitis: 1 gram IV every 8 hours, infused over 30 minutes

Meropenem

<2 All other infections: 2 grams IV every 8 hours, infused over 3 hours

Piperacillin-tazobactam

<16/4

4.5 grams IV every 6 hours, infused over 3 hours Uncomplicated cystitis: 5 mg/kg IV as a single dose

Tobramycin

<1

Pyelonephritis or complicated UTI: 7 mg/kg IV once; subsequent dosing varies by PK evaluation

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Acinetobacter baumannii Carbapenem-resistant Acinetobacter baumannii (CRAB) infections present significant challenges in clinical settings, particularly among hospitalized patients in intensive care units who frequently have multiple comorbidities. These patients have more than double the mortality risk compared to those with carbapenem-susceptible Acinetobacter baumannii infections. The resistance is primarily driven by the presence of carbapenemase genes in Acinetobacter baumannii.10,11 Now, the preferred regimen for Acinetobacter baumannii infections is sulbactam-durlobactam (branded as Xacduro). This combination is recommended because durlobactam enhances the effectiveness of sulbactam by protecting it from being broken down, making it more effective against multidrugresistant Acinetobacter baumannii.12 When sulbactam-durlobactam is not available, ampicillinsulbactam is suggested as an alternative. However, the shift to sulbactam-durlobactam is preferred because it allows for more effective dosing and avoids the need for high doses of sulbactam alone, which is less effective without durlobactam.13 Additionally, using sulbactam-durlobactam helps reduce the reliance on high doses of ampicillin, which is not effective against Acinetobacter baumannii, thus supporting better antibiotic stewardship by minimizing unnecessary use of extra antimicrobials.

Regarding the use of sulbactam-durlobactam, an important discussion point is whether it should be used in combination with a carbapenem, such as imipenem or meropenem.

The effectiveness of this combination therapy remains under investigation, although clinical studies leading to the approval of sulbactam-durlobactam included patients who were also receiving imipenem, likely to ensure broad coverage against other potential pathogens. The IDSA AMR guidance has highlighted the potential synergistic effect of combining these agents, as they target different penicillin-binding proteins (PBPs). This combination could enhance the activity of sulbactam-durlobactam by potentially lowering the minimum inhibitory concentrations (MICs) by up to twofold. Further research is needed to fully understand the benefits of this approach.

Stenotrophomonas maltophilia The most significant change recommended by the IDSA is the removal of ceftazidime from the list of treatment options for Stenotrophomonas maltophilia, following last year’s AMR guidance, which cautioned against relying on ceftazidime susceptibility results due to outdated and insufficient data on clinical effectiveness. Susceptibility testing for ceftazidime has also proven unreliable and inconsistent. These concerns are further compounded by the likelihood of intrinsic β-lactamases that can render the drug ineffective.14 In 2024, the CLSI removed ceftazidime breakpoints for Stenotroph-

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omonas maltophilia, leading the IDSA to advise against using ceftazidime for these infections.

The IDSA 2024 guidance recommends treating Stenotrophomonas using a combination of the following antibiotics based on susceptibility testing; cefiderocol (preferred initially), minocycline, TMP-SMX, and levofloxacin. Tigecycline is a reasonable alternative; however, given favorable pharmacokinetic/pharmacodynamic data, availability in oral formulation, and better tolerability, the panel favors minocycline over tigecycline when feasible. In the event of severe illness, known antimicrobial resistance, or lack of response or tolerance to aforementioned antimicrobials, the recommendation remains to use ceftazidime-avibactam in combination with aztreonam, which are active against multiple types of β-lactamases.

Another significant change in the current guidance document is the recommendation change in TMP-SMX dosing to 10–15mg/kg/day from 8–12mg/kg/day. Doses greater than 15mg/kg/day are associated with increased adverse events, whereas doses between 10–15mg/kg/day should be adequate in achieving bacteriostasis and have a better safety profile.

AmpC β-lactamase producing Enterobacterales Various organisms have the potential for AmpC β-lactamase production included in commonly referenced abbreviations “SPACE/SPICE”. IDSA cautions on potential overestimating of some organisms previously presumed to harbor AmpC such as Serratia marcescens, Morganella morganii, and Providencia species.15-17 In contrast, Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii have moderate risk of AmpC β-lactamase production. In vitro data suggests that up to 20% of these Enterobacterales species exposed to ceftriaxone will lead to the production of AmpC β-lactamases and more so warrant modification of antibiotic selection given higher risk of induction. However, it is important to note, the actual magnitude of AmpC β-lactamase induction overall and its impact on clinical outcomes is limited. There is currently no routine laboratory detection method for presence of AmpC β-lactamases.

Given its properties of being a weak inducer of ampC and a poor substrate of AmpC β-lactamases, cefepime has long been a recommended antibiotic choice for these pathogens. Review of existing literature suggests there is no clear correlation between MIC and ESBL production. Cefepime is therefore still recommended for these Enterobacterales species.

In summary, the 2024 IDSA AMR guidance introduces critical updates that significantly impact the management of resistant gram-negative infections, particularly those caused

by Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The removal of gentamicin for Pseudomonas aeruginosa, the endorsement of high-dose

extended-infusion β-lactams, and the new recommendations for novel agents like ceftolozane-tazobactam and cefiderocol reflect an evolving understanding of antimicrobial resistance and therapy. These revisions emphasize the importance of personalized treatment approaches and the need for clinicians to stay informed about the latest guidance to optimize patient outcomes. Enhanced collaboration with laboratory partners and adherence to these updated recommendations will be crucial in addressing the growing challenge of antimicrobial resistance and improving the management of complex infections, the endorsement of high-dose extended-infusion beta-lactams, and the new recommendations for novel agents like ceftolozane-tazobactam and cefiderocol reflect an evolving understanding of antimicrobial resistance and therapy. These revisions emphasize the importance of personalized treatment approaches and the need for clinicians to stay informed about the latest guidelines to optimize patient outcomes. Enhanced collaboration with laboratory partners and adherence to these updated recommendations will be crucial in addressing the growing challenge of antimicrobial resistance and improving the management of complex infections.

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Victor Chen is an infectious diseases and antimicrobial stewardship pharmacist specialist at UC San Diego Health.

11.

Christopher Baladad is an infectious-diseases-trained pharmacist who practices as a clinical pharmacist UC San Diego Health.

12.

Nina Haste is an infectious diseases and antimicrobial stewardship pharmacist specialist at UC San Diego Health.

13.

Helen Berhane is an infectious diseases and pediatrictrained pharmacist who practices as a clinical pharmacist at UCSD Medical Center, Hillcrest.

14.

Dr. Law is the program director of UC San Diego’s ID Fellowship Training Program and the assistant director of

15.

Epidemiology and ASP, Immunocompromised Services. After completing fellowships in infectious diseases and transplant

16.

infectious diseases, she joined UCSD in 2017, where she focuses on solid organ transplant and oncology infectious diseases.

Dr. Abeles is an infectious diseases physician and medical

17.

Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. Published online August 7, 2024. doi:10.1093/cid/ciae403 Glen KA, Lamont IL. β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects. Pathogens. 2021;10(12):1638. Published 2021 Dec 18. doi:10.3390/pathogens10121638 CLSI. Performance Standards for Antimicrobial Susceptibility Testing.

34rd ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2024.

Dulhunty JM, Brett SJ, De Waele JJ, et al. Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial. JAMA. Published online June 12, 2024. doi:10.1001/jama.2024.9779 de Jonge BL, Karlowsky JA, Kazmierczak KM, Biedenbach DJ, Sahm DF, Nichols WW. In Vitro Susceptibility to Ceftazidime-Avibactam of Carbapenem-Nonsusceptible Enterobacteriaceae Isolates Collected during the INFORM Global Surveillance Study (2012 to 2014). Antimicrob Agents Chemother. 2016;60(5):3163-3169. Published 2016 Apr 22. doi:10.1128/AAC.03042-15 Bauer KA, West JE, O’Brien JM, Goff DA. Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2013;57(7):2907-2912. doi:10.1128/ AAC.02365-12 Tamma PD, Beisken S, Bergman Y, et al. Modifiable Risk Factors for the Emergence of Ceftolozane-Tazobactam Resistance. Clin Infect Dis. Sep 3 2020;doi:10.1093/cid/ciaa1306 Shields RK, Abbo LM, Ackley R, et al. A multicenter, observational study to compare the effectiveness of ceftazidime-avibactam versus ceftolozane-tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the United States (CACTUS). SSRN. Published 2024.

Accessed August 23, 2024. doi:10.2139/ssrn.4891722.

Bassetti M, Echols R, Matsunaga Y, et al. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect Dis. 2021;21(2):226-240. doi:10.1016/S14733099(20)30796-9 Kang HM, Yun KW, Choi EH. Molecular epidemiology of Acinetobacter baumannii complex causing invasive infections in Korean children during 2001-2020. Ann Clin Microbiol Antimicrob. 2023;22(1):32. Published 2023 May 3. doi:10.1186/s12941-023-00581-3 Lemos EV, de la Hoz FP, Einarson TR, et al. Carbapenem resistance and mortality in patients with Acinetobacter baumannii infection: systematic review and meta-analysis. Clin Microbiol Infect. 2014;20(5):416-423. doi:10.1111/1469-0691.12363 Karlowsky JA, Hackel MA, McLeod SM, Miller AA. In Vitro Activity of SulbactamDurlobactam against Global Isolates of Acinetobacter baumanniicalcoaceticus Complex Collected from 2016 to 2021. Antimicrob Agents Chemother. Sep 20 2022;66(9):e0078122. doi:10.1128/aac.00781-22 Bhavnani SM, Rubino CM, Hammel JP, et al. Population pharmacokinetics, pharmacodynamic/pharmacokinetic attainment and clinical pharmacokinetic/pharmacodynamic analysesforsulbactam-durlobactam to support dose selection forthe treatment of Acinetobacter baumanniicalcoaceticusinfections. Abstract LB2306. ID Week 2022, Washington DC. Brooke JS. Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev. Jan 2012;25(1):2-41. doi:10.1128/ CMR.00019-11 Jacobson KL, Cohen SH, Inciardi JF, et al. The relationship between antecedent antibiotic use and resistance to extended-spectrum cephalosporins in group I β-lactamase-producing organisms. Clin Infect Dis. Nov 1995;21(5):1107-13. doi:10.1093/clinids/21.5.1107 Choi SH, Lee JE, Park SJ, et al. Emergence of antibiotic resistance during therapy for infections caused by Enterobacteriaceae producing AmpC β-lactamase: implicationsfor antibiotic use. Antimicrob Agents Chemother.

Mar 2008;52(3):995-1000.

Hardy ME, Kenney RM, Tibbetts RJ, Shallal AB, Veve MP. Leveraging stewardship to promote ceftriaxone use in severe infections with lowand no-risk AmpC Enterobacterales. Antimicrob Agents Chemother. Nov 15 2023;67(11):e0082623. doi:10.1128/aac.00826-23

program director of Antimicrobial Stewardship at UC San Diego Health.

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Candida Auris in San Diego: Enhancing Infection Prevention and Control Efforts

By Loriel Magsino, MPH, CIC and Francesca J. Torriani, MD, FIDSA, AAHIVS AMID THE GLOBAL CRISIS OF MULTIDRUG-RESISTANT

organisms, Candida auris has emerged as a particularly alarming threat, both worldwide and locally in San Diego County. The World Health Organization (WHO) has classified C. auris in the critical priority group of its Fungal Priority Pathogens List because of its ability to cause severe infections with high mortality, multidrug resistance, and challenging identification in laboratories. Moreover, this pathogen’s increasing prevalence, environmental persistence, and potential to cause outbreaks in healthcare facilities have made it a serious global health concern.

Infection prevention and control are crucial for maintaining public health, especially given San Diego’s diverse population and extensive healthcare network. Home to numerous healthcare facilities, infection control in this area is vital to prevent healthcare-associated infections (HAIs). This calls for a multifaceted approach, including consistent hand hygiene, diligent use of personnel protective equipment (PPE), rigorous environmental cleaning, active surveillance, timely reporting, and rapid response to outbreaks. Collaboration between healthcare providers, infection preventionists, and public health officials ensures the consistent implementation of best practices, reducing the risk of transmission, and improving patient outcomes.

First identified in Japan in 2009, C. auris has quickly spread to over 41 countries, causing life-threatening infections and sparking significant outbreaks. The fungi can grow between 37°C to 42°C and in high salinity conditions, which allows it to thrive in diverse environments. It persists on surfaces such as steel, linen, and plastic for days to weeks, which further complicates infection control efforts. Transmission of C. auris has been closely studied through outbreak investigations, particularly in intensive care units (ICUs). Factors that promote its spread include long-term colonization of patients, frequent environmental contamination, biofilm formation, and challenges in laboratory identification. As described by the National Notifiable Diseases Surveillance System (NNDSS), a patient colonized or infected with this pathogen is considered colonized indefinitely and can be a source of infection to others through direct and indirect contact. Contamination is commonly found in patient care areas and on

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medical equipment.

Colonization of patients in healthcare facilities can occur rapidly and may persist for weeks, months, or even years.

Patients with risk factors such as invasive medical devices or prolonged antimicrobial use are at an increased risk of developing infections. Routine testing of certain specimens, such as urine, typically does not include species identification for Candida, as these organisms often do not require specific treatment. However, if a patient is at risk for C. auris due to known exposure or a history of colonization, physicians should consider requesting speciation to ensure appropriate management.

In a 2023 study published in Infection Control & Hospital Epidemiology, de St. Maurice and colleagues examined all hospitalized C. auris cases within the UCLA healthcare system between October 2019 and February 2022. They found a 4% prevalence, with 45 cases identified among 1,129 patients. The median age of the patients was 66 years, and 60% were male.

Notably, every patient had at least one comorbidity, with 82% having a history of tracheostomy, and nearly 90% had been transferred from facilities with known outbreaks. The study also revealed that all isolates were resistant to fluconazole but remained susceptible to echinocandins, supporting their use as the first-line treatment in Los Angeles. Most clinical infections identified were bloodstream infections, with infected patients more likely to have central lines. However, the study found no significant difference in mortality rates between infected and colonized patients. Importantly, all isolates were identified as Clade III, indicating a recent interstate transmission from Florida to Southern California and pointing to a unique lineage circulating in the Los Angeles area during this period. These findings highlight the challenges of controlling C. auris in healthcare settings, especially given its resistance patterns and the additional strain from the COVID-19 pandemic, where factors like PPE reuse, increased antimicrobial use, and longer hospital stays may have further spread the pathogen.

C. auris is a problematic pathogen due to its resistance to multiple antifungal drugs, limiting treatment options and complicating infection management. Most strains resist at least one class of antifungal drugs, with some exhibiting

resistance to all three major classes. The yeast’s ability to form biofilms further increases antifungal tolerance, making management of infections challenging. As an emerging global healthcare threat, it places a significant burden on healthcare systems due to its high morbidity and mortality rates.

Currently, there is no vaccine or effective decolonization strategy for C. auris, making prevention and control necessary. Advanced diagnostic techniques, such as MALDI-TOF MS and real-time PCR, are essential for accurately identifying and detecting colonization, given its phenotypic similarity to other Candida species.

CDPH has implemented strict reporting requirements to better track and manage C. auris cases. Since September 2022, healthcare providers and laboratories have been mandated to report colonization and infections to their local public health authority within one working day of identification. The implementation of these requirements, along with enhanced screening practices, is expected to lead to an increase in reported cases. This reflects both greater awareness and the actual rise in incidence. The surveillance of cases follows specific case definitions outlined by the NNDSS. A clinically confirmed case is identified through confirmatory laboratory evidence from a clinical specimen collected during routine care. A screened confirmed case is identified through a swab collected for screening for colonization, regardless of the site swabbed. These definitions are needed for consistent reporting and understanding the spread of C. auris.

San Diego has experienced a concerning rise in C. auris cases, increasing from 57 in 2022 to 95 in 2023, with 72 confirmed cases by mid-2024. This trend indicates a sharp

increase in local prevalence. Statewide data from the California Department of Public Health (CDPH) shows that from January 2017 to March 2024, San Diego County reported 175 out of 7,493 cases across California. Local transmission of this organism is a growing concern. In 2021, two cases were identified in separate acute care facilities, with no known exposures outside the region. This development marked a shift from previous cases, which had epidemiological links to healthcare facilities outside of San Diego County. This event suggests that local transmission had begun. The escalation of cases has prompted updates to surveillance, screening, and infection control practices. Local public health authorities and infection prevention teams are actively working to mitigate the spread and impact of this emerging pathogen within the area.

Guided by national, state, and local public health authorities, comprehensive infection control strategies have been implemented to curb the spread of C. auris. These efforts include active surveillance, isolation protocols, environmental cleaning, antimicrobial stewardship, and innovative approaches.

Active surveillance plays a key role in identifying this pathogen, with screening protocols focusing on colonized and asymptomatic carriers. Screening involves using axilla and groin swabs for high-risk patients in long-term acute care hospitals (LTACHs), skilled nursing facilities (SNFs) with ventilator units, or those transferred from facilities with known cases or from outside San Diego County. Additionally, acute care hospitals may consider testing patients in highrisk units like ICUs, burn units, or oncology/bone marrow

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transplant wards, especially those with indwelling devices or a history of carbapenemase-producing organisms (CPO).

Testing and prompt reporting are vital to surveillance.

Healthcare facilities must submit sterile site isolates to the County of San Diego Public Health Laboratory within ten days of collection. As a nationally notifiable condition, healthcare providers and laboratories must report cases immediately to local public health departments and the Centers for Disease Control and Prevention (CDC) to facilitate rapid response and containment.

Indefinite transmission-based precautions are required for managing patients with C. auris. Contact isolation or enhanced barrier precautions, ideally in single patient rooms, are recommended to reduce the risk of its spread. Seamless communication between healthcare facilities is imperative to ensure proper disclosure of positive cases. This information should be easily accessible in the electronic medical record (EMR), especially when a patient is transferred from one facility to another. In cases where private rooms are limited, priority is given to patients with uncontained secretions, acute diarrhea, or draining wounds. PPE, including gowns and gloves, is mandatory, and dedicated medical equipment should be used. If equipment must be shared, it must be thoroughly cleaned and disinfected after each use. Isolation precautions are maintained permanently throughout the patient’s stay, transfer, discharge, and any readmissions.

Environmental cleaning is a fundamental element of infection control, especially given this fungi’s resilience on surfaces. Disinfectant products must be on the Environmental Protection Agency’s (EPA) List P, which includes hospitalgrade disinfectants effective against C. auris. Facilities may use EPA-registered disinfectants against Clostridioides difficile spores (List K) as an alternative. However, its ingredients may be corrosive leading to damages in equipment and furniture. It is important to follow the manufacturer’s instructions for use (IFU) to ensure compatibility, proper contact time, and efficacy. Routine daily cleaning and terminal cleaning are needed, particularly in high-risk units like ICUs and ventilator units. Infection prevention teams should collaborate with Environmental Services Department to ensure thorough disinfection of patient areas to prevent the persistence and spread of this pathogen.

Antimicrobial stewardship plays a crucial role in managing C. auris by limiting the overuse of broad-spectrum antibiotics that can contribute to resistance. CDPH and local healthcare facilities have put strong antimicrobial stewardship programs (ASPs) in place to keep a close eye on antibiotic use.

These programs aim to use antibiotics more effectively, helping to prevent resistance and reduce the risk of infections.

San Diego County has also embraced innovative approaches to enhance its infection control efforts. One such initia-

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tive is teaming up with WastewaterSCAN, a CDPH project that monitors wastewater for C. auris. Sewage samples from treatment plants, like the E.W. Blom Point Loma Wastewater Treatment Plant, are tested for the presence of the organism. This dashboard provides valuable data on its community prevalence and serves as an early warning system for potential outbreaks. Additionally, some healthcare facilities use whole genome sequencing (WGS) to help trace transmission by identifying genetic links between cases. This technology can pinpoint infection sources and help track its spread intra- and inter-facilities. Furthermore, EMR tools like patient trace and bed trace programs have proven helpful in outbreak management. They aid in investigating patient movements within the facility, assist in contact tracing, and track the instruments and equipment used.

In conclusion, the growing presence of C. auris in San Diego County requires constant vigilance and strong infection control measures. Given its potential for transmission and serious impact on healthcare settings, it’s crucial for healthcare providers, infection preventionists, and public health authorities to work together. Ongoing surveillance, strict infection control practices, and creative strategies will be key to managing this emerging threat and protecting public health in the area.

Loriel Magsino has been an infection preventionist at UC San Diego Health since December 2021. With a master’s in public health and a certification in infection control, she brings a strong foundation in infection prevention and clinical epidemiology to the role. Through collaboration with multidisciplinary teams and a focus on evidence-based strategies, Loriel continues to drive key initiatives that enhance patient safety and care quality.

Dr. Torriani is a professor of clinical medicine in the Department of Medicine, Division of Infectious Diseases and Global Health at UC San Diego. Her current interests are in implementation science aimed at improving and sustaining high quality and safety in healthcare in cost conscious and reproducible ways, as well as to shape and implement meaningful public health healthcare policies at the national and international levels. Dr. Torriani serves as the program director of UC San Diego Health’s Infection Prevention and Clinical Epidemiology and TB Control, as the chair of the San Diego County Medical Society’s GERM Commission, and at the national level, she chairs the Infectious Diseases Society of America’s Practice and Quality Committee.

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INTERNAL MEDICINE PHYSICIAN: Federally Qualified Health Center located in San Diego County has an opening for an Internal Medicine Physician. This position reports to the chief medical officer and provides the full scope of primary care services, including diagnosis, treatment, and coordination of care to its patients. The candidate should be board eligible and working toward certification in Internal Medicine. Competitive base salary, CME education, Four weeks paid vacation, year one, 401K plan, No evenings and weekends, Monday through Friday 8:00am to 5:00pm. For more information or to apply, please contact Dr. Keith Brady at: uabresearchdoc@yahoo.com.

FAMILY MEDICINE/INTERNAL MEDICINE PHYSICIAN: San Diego Family Care is seeking a Family Medicine/Internal Medicine Physician (MD/DO) at its Linda Vista location to provide outpatient care for acute and chronic conditions to a diverse adult population. San Diego Family Care is a federally qualified, culturally competent and affordable health center in San Diego, CA. Job duties include providing complete, high quality primary care and participating in supporting quality assurance programs. Benefits include flexible schedules, no call requirements, a robust benefits package, and competitive salary. If interested, please email CV to sdfcinfo@sdfamilycare.org or call us at (858) 810-8700.

PHYSICIAN POSITIONS WANTED PART-TIME CARDIOLOGIST AVAILABLE: Dr. Durgadas Narla, MD, FACC is a noninvasive cardiologist looking to work 1-2 days/week or cover an office during vacation coverage in the metro San Diego area. He retired from private practice in Michigan in 2016 and has worked in a San Marcos cardiologist office for the last 5 years, through March 2023. Board certified in cardiology and internal medicine. Active CA license with DEA, ACLS, and BCLS certification. If interested, please call (586) 206-0988 or email dasnarla@gmail.com.

LA JOLLA/XIMED OFFICE TO SUBLEASE: Modern upscale office on the campus of Scripps Hospital — part or full time. Can accommodate any specialty. Multiple days per week and full use of the office is available. If interested please email kochariann@yahoo.com or call (818) 319-5139. [2866-0904] SUBLEASE AVAILABLE: Sublease available in modern, upscale Medical Office Building equidistant from Scripps and Sharp CV. Ample free parking. Class A+ office space/medical use with high-end updates. A unique opportunity for Specialist to expand reach into the South Bay area without breaking the bank. Specialists can be accommodated in this first floor high-end turnkey office consisting of 1670 sq ft. Located in South Bay near Interstate 805. Half day or full day/week available. South Bay is the fastest growing area of San Diego.

Successful sublease candidates will qualify to participate in ongoing exclusive quarterly networking events in the area.

Call Alicia, 619-585-0476.

OFFICE SPACE FOR SUBLEASE | SOUTHEAST SAN DIEGO: 3 patient exam rooms, nurse’s station, large reception area and waiting room. Large parking lot with valet on-site, and nearby bus stop. 286 Euclid Ave - Suite 205, San Diego, CA 92104. Please contact Dr. Kofi D. Sefa-Boakye’s office manager: Agnes Loonie at (619) 435-0041 or ams66000@aol. com. [2869-0801] MEDICAL OFFICE FOR SALE OR SUBLEASE: A newly remodeled and fully built-out primary care clinic in a highly visible Medical Mall on Mira Mesa Blvd. at corner of Camino Ruiz. The office is approximately 1000 sq ft with 2 fully equipped exam rooms, 1 office, 1 nurse station, spacious and welcoming waiting room, spacious reception area, and ADA accessible restroom. All the furniture and equipment are new and modern design. Ample parking. Perfect for primary care or any specialty clinic. Please contact Nox at 619-776-5295 or noxwins@hotmail.com. Available immediately.

RENOVATED MEDICAL OFFICE AVAILABLE | EL CAJON: Recently renovated, turn-key medical office in freestanding single-story unit available in El Cajon. Seven exam rooms, spacious waiting area with floor-to-ceiling windows, staff break room, doctor’s private office, multiple admin areas, manager’s office all in lovely, drought-resistant garden setting.

Ample free patient parking with close access to freeways and Sharp Grossmont and Alvarado Hospitals. Safe and secure with round-the-clock monitored property, patrol, and cameras. Available March 1st. Call 24/7 on-call property manager Michelle at the Avocado Professional Center (619) 916-8393 or email help@avocadoprofessionalcenter.com.

OPERATING ROOM FOR RENT: State of the Art AAAASF Certified Operating Rooms for Rent at Outpatient Surgery of Sorrento. 5445 Oberlin Drive, San Diego 92121. Ideally located and newly built 5 star facility located with easy freeway access in the heart of San Diego in Sorrento Mesa. Facility includes two operating rooms and two recovery bays, waiting area, State of the Art UPC02 Laser, Endoscopic Equipment with easy parking. Ideal for cosmetic surgery. Competitive Rates. Call Cyndy for more information 858.658.0595 or email Cyndy@ roydavidmd.com.

PRIME LOCATION | MEDICAL BUILDING LEASE OR OWN OPPORTUNITY IN LA MESA: Extraordinary opportunity to lease or lease-to-own a highly visible, freeway-oriented medical building in La Mesa, on Interstate 8 at the 70th Street on-ramp. Immaculate 2-story, 7.5k square foot property with elevator and ample free on-site parking (45 spaces). Already built out and equipped with MRI/CAT machine. Easy access to both Alvarado and Sharp Grossmont Hospitals, SDSU, restaurants, and walking distance to 70th St Trolley Station.

Perfect for owner-user or investor. Please contact Tracy Giordano [Coldwell Banker West, DRE# 02052571] for more information at (619) 987-5498.

POWAY MEDICAL OFFICE SPACE FOR LEASE: Fully built out, turnkey 1257 sq ft ADA-compliant suite for lease.

Great location in Pomerado Medical/Dental Building, next to Palomar Med Center Poway campus. Building restricted to medical/allied health/dental practices, currently houses ~26 suites. Ideal for small health practice as primary or satellite location. Lease includes front lobby, reception area, restrooms, large treatment area, private treatment/exam rooms. Located on second floor, elevator/stair access. Bright, natural lighting; unobstructed views of foothills. On-site parking; nearby bus service. Flexible lease terms available from 3-5 years at fair market rate. Contact Debbie Summers at debjsummers3@ gmail.com or (858) 382-8127. [2856-1101] KEARNY MESA OFFICE TO SUBLEASE/SHARE: 5643 Copley Dr., Suite 300, San Diego, CA 92111. Perfectly centrally situated within San Diego County. Equidistant to flagship hospitals of Sharp and Scripps healthcare systems. Ample free parking. Newly constructed Class A+ medical office space/ medical use building. 12 exam rooms per half day available for use at fair market value rates. Basic communal medical

supplies available for use (including splint/cast materials). Injectable medications and durable medical equipment (DME) and all staff to be supplied by individual physicians’ practices.

1 large exam room doubles as a minor procedure room. Ample waiting room area. In office x-ray with additional waiting area outside of the x-ray room. Orthopedic surgery centric office space. Includes access to a kitchenette/indoor break room, exterior break room and private physician workspace.

Open to other MSK physician specialties and subspecialties.

Building occupancy includes specialty physicians, physical therapy/occupational therapy (2nd floor), urgent care, and 5 OR ambulatory surgery center (1st floor). For inquiries contact kdowning79@gmail.com and scurry@ortho1.com for more information. Available for immediate occupancy.

LA JOLLA/UTC OFFICE TO SUBLEASE OR SHARE: Modern upscale office near Scripps Memorial, UCSD hospital, and the UTC mall. One large exam/procedure room and one regular-sized exam room. Large physician office for consults as well. Ample waiting room area. Can accommodate any specialty or Internal Medicine. Multiple days per week and full use of the office is available. If interested please email drphilipw@gmail.com.

ENCINITAS MEDICAL SPACE AVAILABLE: Newly updated office space located in a medical office building. Two large exam rooms are available M-F and suitable for all types of practice, including subspecialties needing equipment space.

Building consists of primary and specialist physicians, great for networking and referrals. Includes access to the break room, bathroom and reception. Large parking lot with free parking for patients. Possibility to share receptionist or bring your own. Please contact coastdocgroup@gmail.com for more information.

NORTH COUNTY MEDICAL SPACE AVAILABLE: 2023 W. Vista Way, Suite C, Vista CA 92082. Newly renovated, large office space located in an upscale medical office with ample free parking. Furnishings, decor, and atmosphere are upscale and inviting. It is a great place to build your practice, network and clientele. Just a few blocks from Tri-City Medical Center and across from the urgent care. Includes: multiple exam rooms, access to a kitchenette/break room, two bathrooms, and spacious reception area all located on the property. Wi-Fi is not included. For inquiries contact hosalkarofficeassist@ gmail.com or call/text (858)740-1928.

MEDICAL EQUIPMENT / FURNITURE FOR SALE UROLOGY OFFICE CLOSING 6/2023 | EQUIPMENT AVAILABLE: Six fully furnished exam rooms including tables (2 bench, 3 power chair/table, 1 knee stirrup), rolling stools, lights, step stools, patient chairs. Waiting room chairs, tables, magazine rack. Specialty items—Shimadzu ultrasound, SciCan sterilizer, Dyonics camera with Sharp monitor, Medtronic Duet urodynamics with T-DOC catheters, Bard prostate biopsy gun with needles, Cooper Surgical urodynamics, Elmed ESU cautery, AO 4 lens microscope. RICOH MP-3054 printer with low print count. For more information contact: r.pua@cox.net.

NON-PHYSICIAN POSITIONS AVAILABLE POSTDOCTORAL SCHOLARS: The Office of Research Affairs, at the University of California, San Diego, in support of the campus, multidisciplinary Organized Research Units (ORUs) https://research.ucsd.edu/ORU/index.html is conducting an open search for Postdoctoral Scholars in various academic disciplines. View this position online: https://apolrecruit.ucsd.edu/JPF03803. The postdoctoral experience emphasizes scholarship and continued research training.

UC’s postdoctoral scholars bring expertise and creativity that enrich the research environment for all members of the UC community, including graduate and undergraduate students.

Postdocs are often expected to complete research objectives, publishing results, and may support and/or contribute expertise to writing grant applications https://apol-recruit.ucsd. edu/JPF03803/apply. [2864-0808] RESEARCH SCIENTISTS (NON–TENURED, ASSISTANT, ASSOCIATE OR FULL LEVEL): The University of California, San Diego campus multidisciplinary Organized Research Units (ORUs) https://research.ucsd.edu/ORU/index.html is conducting an open search for Research Scientists (non–tenured, assistant, associate or full level). Research Scientists are extramurally funded, academic researchers who develop and lead independent research and creative programs similar to Ladder Rank Professors. They are expected to serve as Principal Investigators on extramural grants, generate high caliber publications and research products, engage in university and public service, continuously demonstrate independent, high quality, significant research activity and scholarly reputation.

Appointments and duration vary depending on the length of the research project and availability of funding. Apply now at https://apol-recruit.ucsd.edu/JPF03711. [2867-0904] PROJECT SCIENTISTS: Project Scientists (non-tenured, Assistant, Associate or Full level): The University of California, San Diego, Office of Research and Innovation https://research.ucsd.edu/, in support of the Campus multidisciplinary Organized Research Units (ORUs) https://research.ucsd. edu/ORU/index.html is conducting an open search. Project Scientists are academic researchers who are expected to make significant and creative contributions to a research team, are not required to carry out independent research but will publish and carry out research or creative programs with supervision. Appointments and duration vary depending on the length of the research project and availability of funding: https://apol-recruit.ucsd.edu/JPF03712/apply. [2868-0904]

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