
Acute coccidioidomycosis in an immunocompetent host


A 37-year-old male patient presented to the emergency department with severe bilateral lower-extremity pain that prevented him from walking. Over one week, he developed progressively worsening bilateral knee tenderness and painful red bumps over his shins (

). Additionally, he reported a new 2-day history of dry cough and subjective fever.


Three weeks prior to presentation, the patient had emigrated from Guatemala, crossing the US-Mexico border, where he spent 7 days in the Arizona desert. Subsequently, he relocated to New York, where he began to develop symptoms. He denied any recent insect bites, exposure to any animals, or a history of tuberculosis. He further denied alcohol, tobacco, or illicit substance use. He was sexually active with his wife. At the time of presentation, he was employed as a construction worker. Family history was noncontributory.


The patient was a well-developed and well-nourished male in no acute distress. He was saturating well on room air with hemodynamically stable vital signs. His cardiac exam was unremarkable. A pulmonary exam revealed decreased breath sounds at the right upper lobe and dry cough with deep inspiration. The patient had diffuse erythema over both knees, which were tender to palpation. Additionally, he had several dime-sized erythematous subcutaneous nodules over his bilateral shins, which were also painful to the touch.


On laboratory assessment, the patient was found to have a white blood cell count of 11.6 K/mm3 (50% neutrophils, 6.6% eosinophils; reference value: 4.5-10.8 K/mm3); hemoglobin, 12.5 g/dL (12.3-16.0 g/dL); hematocrit, 38.5% (38%-47%); platelet count, 411 K/mm3 (150-410 K/mm3); blood urea nitrogen, 9 mg/dL (6-22 mg/dL); creatinine, 0.84 mg/dL (0.5-1.5 mg/dL); aspartate aminotransferase, 26 U/L (4-35 U/L); alanine aminotransferase, 28 U/L (6-55 U/L); alkaline phosphatase, 105 U/L (40-150 U/L); and erythrocyte sedimentation rate, 41 mm/h (0-10 mm/h).


The patient’s dry cough prompted a chest radiograph that showed a right upper-lobe opacity. Given the patient’s travel history, lung infiltrate, and skin findings, infectious differential diagnoses included endemic fungal infections such as 

, histoplasmosis, coccidioidomycosis, or blastomycosis. Bacterial etiologies including tuberculosis were considered as well. Because he was hemodynamically stable and not appearing septic, antibiotics were deferred until his work-up was completed. His skin findings were diagnosed as erythema nodosum based on their appearance and anatomic location without performing a skin biopsy. The patient was managed with supportive care until the results of diagnostic testing were obtained, and he was started on appropriate therapy prior to discharge.

) showed a wedge-shaped, peripheral nodular focus in the posterior segment of the right upper lobe (25×22×20 mm). A 

enzyme-linked immunosorbent assaywas positive for IgM 1.8 (positive 

 antibody test by complement fixation was positive with a titer of 1:8. Other tests including QuantiFERON-TB Gold, 


Due to his inability to walk and perform his job as a construction worker, the patient was started on fluconazole 400 mg daily for 8 weeks. At the patient’s 2-week follow-up, his symptoms were markedly improved with near complete resolution of his erythema nodosum (

). His erythrocyte sedimentation rate decreased from 41 mm/h to 7 mm/h after 1 month of treatment. The patient was able to return to full duty at work.


Coccidioidomycosis, known colloquially as “Valley Fever,” is a systemic fungal infection caused by the fungi 

. The region most highly endemic for exposure to 

is in the Arizona counties on the US-Mexico border. Additionally, the state of California has seen a large rise in number of cases over the past few decades, including in the prison system population.

 Upon disruption of uninhabited soil by natural disaster or human activity, 

 arthroconidia are released and become airborne. Fluctuations in temperature and precipitation associated with seasonal change in both Arizona and California have been correlated with greater fungal growth and spore dissemination as well as increased incidence of infection.

 Furthermore, global climactic changes including increasing temperatures, wind speeds, aridity, and frequency of wildfires may worsen the disease burden of endemic fungal infections.

 This will continue to be relevant among individuals of lower socioeconomic status and immigrant populations

 who often find work in these areas. Because many of these patients are undocumented and live transiently in endemic regions, the incidence of infectious mycoses may be underreported.

Coccidioidomycosis may present with a wide range of clinical manifestations, from asymptomatic or a mild febrile flu-like illness to pulmonary infection and, less commonly, severe life-threatening disseminated disease. Pulmonary disease can resemble a typical lobar community-acquired pneumonia (CAP), and in endemic regions, up to 25% of patients presenting with CAP will have Coccidioidomycosis.

 Alternatively, pulmonary infiltration can be diffuse and reticulonodular in appearance. In addition to the classic pulmonary findings, roughly 50% of patients with symptomatic coccidioidomycosis will have cutaneous manifestations.

For our patient, the inability to work was secondary to severe arthralgias and pain associated with erythema nodosum (EN), an immunological disorder of subcutaneous nodules and the most common form of panniculitis.

 EN is often the presenting skin finding of a systemic inflammatory illness.

 Bacterial or fungal infection, inflammatory bowel disease, tuberculosis, sarcoidosis, cancer, or drugs may be the underlying cause, activating a delayed-type hypersensitivity reaction. Streptococcal pharyngitis accounts for 30% to 50% of EN cases in adults.

 In coccidioidomycosis, EN is the most common cutaneous finding, typically 1 to 3 weeks after the onset of pulmonary symptoms.

 On biopsy, no pathogens are seen within the soft tissue, which typically shows granulomatous inflammation, septal fibrosis, and mononuclear infiltrate. Interestingly, the presence of EN in patients with coccidioidomycosis confers a favorable prognosis due to a suggested immune response.

Caring for the immigrant community can be challenging, and as physicians, we must be aware of the hazards and exposures our patients experience before they arrive at their destination. The worsening political landscape of Central and South America will continue to place more individuals at risk for potential exposure to coccidioidomycosis and other endemic infections during lengthy and arduous travel. Obtaining an appropriate travel history for our patient who came across the southern border of the United States triggered a fungal work-up and, ultimately, a diagnosis of acute coccidioidomycosis. We were thus able to avoid the unnecessary use of antibiotics while providing the appropriate drug therapy and follow-up. Coccidioidomycosis should be considered part of the differential diagnosis of any hospitalized immigrant who has traveled across the southern border of the United States. To our knowledge, this entity is underrecognized and underreported in the immigrant community.

PAPPAGIANIS, D. & LABORATORY, the C. S. Coccidioidomycosis in California State Correctional Institutions. 

Annals of the New York Academy of Sciences

Brown, J., Benedict, K., Park, B. J. & Thompson 3rd, G. R. Coccidioidomycosis: epidemiology. 

Weaver, E. A. & Kolivras, K. N. Investigating the Relationship Between Climate and Valley Fever (Coccidioidomycosis). 

van Rhijn, N. & Bromley, M. The Consequences of Our Changing Environment on Life Threatening and Debilitating Fungal Diseases in Humans. 

 An Epidemic of Coccidioidomycosis in Arizona Associated with Climatic Changes, 1998–2001. 

Shriber, J., Conlon, K. C., Benedict, K., McCotter, O. Z. & Bell, J. E. Assessment of Vulnerability to Coccidioidomycosis in Arizona and California. 

International journal of environmental research and public health

Dzau, V. J., Levine, R., Barrett, G. & Witty, A. Decarbonizing the U.S. Health Sector — A Call to Action. 

White Jr., A. C. & Atmar, R. L. Infections in Hispanic Immigrants. 

 Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia. 

 Coccidioidomycosis and the skin: a comprehensive review. 

Pérez-Garza, D. M., Chavez-Alvarez, S., Ocampo-Candiani, J. & Gomez-Flores, M. Erythema Nodosum: A Practical Approach and Diagnostic Algorithm. 

Schwartz RA & Nervi SJ. Erythema nodosum: a sign of systemic disease. 

Articles

Case Study

Case Study: Acute Coccidioidomycosis Acquired Crossing the US-Mexico Border

According to the World Health Organization, approximately 49 million cases of sepsis are reported globally, resulting in nearly 11 million deaths per year.

 For those who do survive the initial infection, only half will make a full recovery, and the other half will die from resulting complications and disabilities. As new studies continue to highlight the importance of proper sepsis care, it’s critical that clinicians have access to the most up-to-date information. The COVID-19 pandemic has only magnified the importance of having reliable resources for clinicians, especially since COVID-19 and sepsis care can overlap. When care teams have access to the best clinical tools and updated studies, they know when and where to allocate resources during a crisis and can collectively work toward delivering the best, impartial care to all patients.

Patients with sepsis are often treated with supplementary oxygen and closely monitored to track sepsis progression, which can be fatal if not caught early. COVID-19 has increased the use of certain measures like pulse oximetry, which measures oxygen in the blood; however, in February, the FDA issued a warning about the limitations and risk of inaccuracy with pulse oximeters in patients of color.

 In addition, 2 articles recently revealed a substantial knowledge gap that may affect sepsis evaluation in Black patients or people with dark skin tone, which could impact subsequent treatment plans.

) published a study that found patients who identified as Black had nearly 3 times the frequency of occult hypoxemia (abnormally low oxygen concentration in the blood) that was not detected by pulse oximetry.

 examined the impact that race can have on the accuracy of the Sequential Organ Failure Assessment (SOFA) score for in-hospital mortality.

 According to the study, the SOFA score overestimated mortality in Black patients compared with White patients, which in times of crisis could result in allocation of resources that favor White patients.

Both studies point to a need to be more discerning of the measures we’re currently using to identify and diagnose sepsis and to understand racial disparities in the assessments used for sepsis diagnosis. These disparities can potentially result in life-threatening impacts when patients should be escalated to intensive care but are improperly diagnosed by frontline care teams.

Identifying Racial Disparities in Sepsis: New Research

 are incredibly important because pulse oximetry is a critical tool for the early evaluation of sepsis and can influence treatment plans. For example, low or borderline pulse oximetry results may prompt theclinician to perform an arterial blood gas (ABG) test, which is a more accurate way to measure oxygenation. With a discrepancy in detecting low readings for Black patients, the clinician may be misled into thinking that the patient’s oxygen level is acceptable and does not require an ABG.

 article are also a cause for concern. If Black patients receive a higher SOFA score than White patients, they are deemed to have a higher mortality rate and less likely to survive sepsis. This information is incredibly important in times of crisis when the SOFA scores may potentially be used to dictate the allocation of health care resources during the activation of crisis standards of care (CSC). 

During the COVID-19 pandemic, medical resources were in short supply, and some intensive care units needed to activate CSC to decide how to allocate medical equipment and resources to maximize patient care. When CSC is activated, this means that health care resources are directed to patients more likely to survive (eg, those with sepsis who have a lower SOFA score).

Both studies suggest potential for Black patients with sepsis to not receive the same level of care and life-saving resources needed to manage sepsis or other critical conditions. Clinicians need to have the educational tools and latest clinical guidance available that allow them to account for the difference in results between Black and White patients to prevent the often-unintentional disproportionate allocation of medical resources and equipment to White patients.

Although hypothetical, it may be deduced that if sepsis is not being identified and treated as diligently in Black or dark skin–toned patients, antibiotic therapy may be delayed and not administered until the patient is clinically sicker, which further compounds the undertreatment of sepsis in Black patients.

Closing Clinical Knowledge Gaps Through Education

Inequitable care has come under scrutiny recently and has highlighted the need for better ways to assess patients of different skin colors as well as the need for additional clinician education. The COVID-19 pandemic exemplified the need for up-to-date data, which can affect decision-making during CSC activation.

It is essential that hospitals facilitate open discussion to help foster awareness among physicians and health care workers about the overreliance on oximetry and underuse of the SOFA score for clinical decision-making. Care teams need to be armed with knowledge and awareness of how health care has left gaps and health disparities for Black patients, especially for life-threatening infections like sepsis. By combining access to updated studies and resources and proactively educating care teams to identify areas of unconscious bias in health care, hospitals can get one step closer to providing all patients equal care, regardless of skin color.

WHO calls for global action on sepsis – cause of 1 in 5 deaths worldwide. News release. World Health Organization. September 8, 2020. Accessed November 2, 2021. 

https://www.who.int/news/item/08-09-2020-who-calls-for-global-action-on-sepsis---cause-of-1-in-5-deaths-worldwide

Pulse oximeter accuracy and limitations: FDA safety communication. FDA. February 19, 2021. Accessed November 2, 2021. 

https://www.fda.gov/medical-devices/safety-communications/pulse-oximeter-accuracy-and-limitations-fda-safety-communication

Sjoding MW, Dickson RP, Iwashyna TJ, Gay SE, Valley TS. Racial bias in pulse oximetry measurement. 

 2020;383(25):2477-2478. doi:10.1056/NEJMc2029240

Miller WD, Han X, Peek ME, Charan Ashana D, Parker WF. Accuracy of the sequential organ failure assessment score for in-hospital mortality by race and relevance to crisis standards of care. 

 2021;4(6):e2113891. doi:10.1001/jamanetworkopen.2021.13891

Stewardship and Prevention

Risk of inaccuracy with pulse oximeters and clinician knowledge gaps in people of color may affect sepsis evaluations and impact treatment plans.

Identifying Disparities in Sepsis Diagnosis for Unbiased Care

In January, the FDA approved the first long-acting injectable (LAI) anti-
retroviral regimen, cabotegravir/rilpivirine (Cabenuva), for maintenance of HIV-1 suppression. The approval was based on results from the phase 3 ATLAS (NCT02951052) and FLAIR (NCT02938520) studies demonstrating that cabotegravir/rilpivirine, administered as 2 intramuscular gluteal injections once monthly, was noninferior to standard oral therapy in maintaining virologic suppression.

Approval of this novel antiretroviral therapy (ART) for treatment simplification represents a revolutionary milestone in the HIV treatment paradigm. For eligible patients, this therapy may offer a solution for improved medication adherence and improved clinical outcomes. Furthermore, it offers convenience and potential for improved quality of life for people with HIV by reducing pill fatigue and stigma associated with HIV. In an exploratory end point assessing patient preference, data from clinical trials demonstrated that most patients (88%) preferred LAI cabotegravir/rilpivirine to their previous oral regimen at week 48 despite the high incidence of mild to moderate injection-site reactions (84%).

With the long-awaited official stamp of approval, ambulatory clinics and health care systems across the US are now focused on successful and sustainable implementation. Because this represents a major shift in HIV treatment as we know it, attention to potential clinical and logistical challenges is essential prior to widespread implementation. Certain aspects of therapy, including strict clinical criteria for use, administration by a health care provider, and initiation of an oral lead-in prior to injection to ensure tolerability, are unfamiliar concepts and necessitate thorough patient, provider, and staff education.

The following article will review key clinical and logistical factors to take into consideration prior to rollout of LAI cabotegravir/rilpivirine and offer solutions to barriers that may arise.

Use of LAI cabotegravir/rilpivirine requires careful consideration for potential clinical risks. Similar to other long-acting medications, management of adverse effects can be challenging because drug levels may persist in the body for several months. However, unlike other long-acting agents for other chronic conditions, there is a risk for treatment failure and development of HIV resistance if patient eligibility is not assessed prior to use or if injection appointments are missed.

Prior to prescribing, it’s essential to confirm patients meet the following clinical criteria: on stable ART with an undetectable viral load (< 50 copies/mL), no known or suspected resistance to cabotegravir or rilpivirine, no prior treatment failure, not pregnant or planning to become pregnant, and not coinfected with hepatitis B virus (HBV) unless receiving additional oral medication for treatment of HBV. A comprehensive chart review should be performed to assess patient eligibility and ensure no contraindications exist. Ideal candidates are those who have consistently attended provider visits because it will now be necessary to attend monthly visits for medication administration, which should be incorporated into patient education materials and counseling sessions. An updated medication list should be obtained, and assessment for potential drug-drug interactions should also be performed. Certain interactions require attention with oral rilpivirine and cabotegravir but are not clinically relevant with injectable therapy because gastrointestinal (GI) absorption is bypassed. For example, oral rilpivirine requires an acidic GI environment for absorption and concomitant use with omeprazole is contraindicated, but absorption is not impacted when rilpivirine is administered intramuscularly. The same is true for cabotegravir and polyvalent cations, as chelation can occur with oral cabotegravir.

Another major clinical consideration for use is the risk of virologic rebound and development of HIV resistance if injection appointments are missed. Maintenance injections can be administered up to 7 days before or after the scheduled monthly injection. For planned missed doses beyond this 7-day window, patients should be bridged with oral cabotegravir and rilpivirine until their next injection can be administered. If it has been 2 months or less since the last injection, maintenance dose injectable therapy can be continued; however, if more than 2 months have passed, the loading dose must be repeated. If unplanned missed doses occur, patients can have detectable but subtherapeutic levels of cabotegravir and rilpivirine for many months after an injection, generating risk for drug resistance. Data from the ATLAS and FLAIR trials demonstrated that resistance rates were similar across both arms with only 3 patients in the LAI cabotegravir/rilpivirine group developing resistance mutations in each trial. The most common mutations were E138K (rilpivirine resistance), which developed in 4 patients across both trials, and Q148R (cabotegravir resistance), which developed in 2 patients in the ATLAS trial.

 A combination of at least 2 of the following baseline factors may be associated with an increased risk of virologic failure: archived rilpivirine-resistance mutations, HIV-1 subtype A6/A1, or body mass index (BMI) equal to or greater than 30 kg/m2.

In addition to clinical considerations, successful implementation of LAI cabotegravir/rilpivirine requires attention to potential logistical barriers. There are several logistical barriers related to medication access. Unlike traditional ART, which is covered through pharmacy benefits, LAI cabotegravir/rilpivirine may be covered under pharmacy and/or medical benefits. Clinics may need to establish new workflows to investigate medical benefits for medication coverage.

Medication procurement is also not straightforward; the oral lead-in is only available from a mail-order specialty pharmacy (TheraCom Pharmacy). This may complicate initiating therapy and bridging patients for missed visits, as medication delivery will require additional coordination. For example, if a patient has an unplanned missed visit, they cannot go to their local pharmacy to obtain additional oral cabotegravir and rilpivirine. The clinic and the patient must reach out to TheraCom and await mail delivery of medication, which could delay access.

New processes will need to be developed for obtaining LAI cabotegravir/rilpivirine. If it is covered under pharmacy benefits, clinics will need to determine if they will utilize white, brown, or clear bagging. Obtaining the medication from an internal pharmacy (clear bagging) may be the most feasible, if possible. However, clinics may also require patients to obtain medication from an outside pharmacy and bring it into the clinic for administration (brown bagging) or may request office delivery through an external pharmacy (white bagging). If the injection is white bagged, then clinics will need to develop a procedure for medication disposal upon missed visits because the external pharmacy may not accept the medication for return. If it is covered under medical benefits, practices will need to set up a process for buy and bill—buying the medication from a pharmacy and then subsequently billing a patient’s medical insurance after administration. Lastly, LAI cabotegravir/rilpivirine must be stored under refrigeration until the time of administration. Brown bagging is generally not recommended because it would require the patient to transport the medication under refrigerated conditions, which may not be possible for all patients. Additional refrigeration space within the clinic may be needed depending on the volume of patients.

LAI cabotegravir/rilpivirine may also increase the consumption of human resources and office space. It may be necessary to provide training sessions on injection preparation and administration prior to implementation. Each monthly administration visit will likely require 30 to 45 minutes for checking in patients, rooming, bringing the medication to room temperature, monitoring post injection, and checking out. This will increase demand for exam rooms and demand on support-staff time (secretaries, medical assistants, and nurses). Support staff may also be responsible for patient tracking, coordination of patient transportation, appointment reminders, and periodic patient follow-up. Furthermore, it may be necessary to purchase additional supplies. For example, a longer needle (which is not included in the dosing kit) may be required for intramuscular administration to individuals with a BMI equal to or greater than 30 kg/m.

To tackle these clinical and logistical challenges, a multidisciplinary approach to implementation is key. Results from the CUSTOMIZE study (NCT04001803) emphasize the importance of teamwork and staff communication and outline key strategies for patient adherence and successful clinic implementation of LAI cabotegravir/rilpivirine.

 In addition to the strategies highlighted in this study, clinics may also consider developing a protocol outlining patient eligibility criteria for LAI cabotegravir/rilpivirine to assist with identification of appropriate candidates. Incorporating a process for prescreening to confirm eligibility by assessing adherence, resolving drug-drug interactions, constructing treatment history, and reviewing the results of resistance testing may be beneficial. Clinical pharmacists are well positioned to conduct this type of review. Clinics with collaborative practice agreements in place could also incorporate this process into their agreements to decrease burden on providers and improve sustainability.

Patient counseling and appropriate tracking/follow-up are also essential, as demonstrated in the CUSTOMIZE study. A counseling session should review the 7-day dosing window, assess potential barriers to adherence to monthly clinic visits, and provide solutions to overcome these obstacles. There should be designated staff members to track patient appointments and a system in place to remind patients of upcoming appointments and follow-up appointments if scheduled visits are cancelled. Clinics can rely on web-based treatment planners or leverage information technology (IT) and electronic health record resources to reduce the burden of patient tracking. For example, IT may be able to develop reports or construct a dashboard for all patients on LAI cabotegravir/rilpivirine and highlight patients who are overdue for an administration. Even with these processes in place, patients may need rapid initiation of the oral components (bridging) or alternative oral ART, which should be made readily available in these situations. If resistance is suspected, it may be prudent to empirically initiate oral therapy with a high genetic barrier to resistance (twice-daily dolutegravir or a boosted protease inhibitor–based regimen) while awaiting resistance testing results, but this decision should be based on patient-specific factors and resistance history.

Additional staffing support may be required to overcome logistical barriers. Scheduling administration visits can be optimized to off-peak clinic days and times. Depending on the clinic model, pharmacists, pharmacy technicians, medical assistants, and/or nurses can assess insurance coverage and address medication procurement. The manufacturer of LAI cabotegravir/rilpivirine, ViiV Healthcare, also provides benefit investigation services. Social workers can potentially assist patients with barriers to transportation. Despite these potential barriers, the CUSTOMIZE study demonstrated that most providers (78%) were able to successfully implement LAI cabotegravir/rilpivirine at their practice or clinic within 1 to 3 months.

LAI cabotegravir/rilpivirine offers a convenient and liberating treatment option to patients with HIV for maintenance of virologic suppression. Replacing daily oral therapy with 12 monthly injections may facilitate adherence and improve overall well-being. To ensure clinical success and minimize risks, clinics may need to incorporate the following into their practices: a tool for identifying eligible patients, an outline for key patient counseling points prior to therapy initiation, and a mechanism for patient tracking and follow-up upon missed injection appointments. Establishing processes for medication acquisition, billing, and on-site medication storage and anticipating the need for additional staffing are essential logistical considerations. In addition, developing a multidisciplinary team and assigning roles for each step in the process will promote successful implementation.

Ongoing studies are evaluating the elimination of oral lead-in and extending administration of LAI cabotegravir/rilpivirine to every 8 weeks, which may decrease medication access barriers in the future and reduce the number of injection visits by 50%.

Ann-Marie Idusuyi, PharmD, is a clinical specialist in infectious diseases at The Miriam Hospital Infectious Diseases and Immunology Center in Providence, Rhode Island. She is a member of Making a Difference in Infectious Diseases and the Society of Infectious Diseases Pharmacists. Her clinical interests include HIV, outpatient parenteral antimicrobial therapy, and treatment of infections in immunocompromised hosts.

Rajeev Shah, PharmD, AAHIVP, BCIDP, is a clinical pharmacy specialist in infectious diseases at The Miriam Hospital Infectious Diseases and Immunology Center and an assistant professor of medicine for the Warren Alpert Medical School of Brown University, both in Providence, Rhode Island. He is also a committee member for the American College of Clinical Pharmacy HIV Practice Research Network Newsletter Committee and the Society of Infectious Diseases Pharmacists Publications and Podcast Committee.

Amy L. Brotherton, PharmD, AAHIVP, BCIDP, is a clinical pharmacist specialist in infectious diseases at The Miriam Hospital Infectious Diseases and Immunology Center and an assistant professor of medicine for the Warren Alpert Medical School of Brown University, both in Providence, Rhode Island. She is also a committee member for American College of Clinical Pharmacy HIV Practice Research Network Advocacy Committee. She is also an active member of the Society of Infectious Diseases Pharmacists and of Making a Difference in Infectious Diseases.

Cabenuva. Prescribing information. ViiV Healthcare; 2021. Accessed November 5, 2021.

https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Cabenuva/pdf/CABENUVA-PI-PIL-IFU2-IFU3.PDF

Rizzardini G, Overton ET, Orkin C, et al. Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. 

. 2020;85(4):498-506. doi:10.1097/QAI.0000000000002466

Swindells S, Andrade-Villanueva JF, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. 

. 2020;382(12):1112-1123. doi:10.1056/NEJMoa1904398

Orkin C, Arasteh K, Górgolas Hernández-Mora M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. 

. 2020;382(12):1124-1135. doi:10.1056/NEJMoa1909512

Czarnogorski M, Garris G, D’Amico R, et al. Customize: overall results from a hybrid III implementation-effectiveness study examining implementation of cabotegravir and rilpivirine long-acting injectable for HIV treatment in US healthcare settings; final patient and provider data. Presented at: 11th International AIDS Society Conference on HIV Science; July 18-21, 2021; virtual. Accessed November 5, 2021. https://www.natap.org/2021/IAS/IAS_27.htm

D’Amico R, Orkin C, Morell EB, et al. Safety and efficacy of cabotegravir + rilpivirine long-acting with and without oral lead-in: FLAIR week 124 results. Presented at: HIV Glasgow 2020 Virtual; October 5-8, 2020. Accessed November 5, 2021. https://www.natap.org/2020/GLASGOW/GLASGOW_45.htm

Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomized, multicentre, open-label, phase 3B, non-inferiority study. 

. 2021;396(10267):1994-2005. doi:10.1016/S0140-6736(20)32666-0

HIV / AIDS

This novel therapeutic option represents the first long-acting injectable approved for maintenance of HIV-1 suppression.

Ready, Set, Cabenuva: Implementing Cabotegravir/Rilpivirine

For clinicians who haven’t dealt with it, 

, the emerging antimicrobial-resistant fungal “superbug” that causes severe illness and outbreaks in health care facilities, may seem like a zebra. However, the situation has evolved over the past 5 years since 

 was first detected in the United States in 2016. No longer restricted to New York and Chicago metropolitan areas, this multidrug-resistant organism (MDRO) is increasingly prevalent in several US regions, including California, Florida, and areas in the mid-Atlantic and Midwest.

We’re increasingly seeing cases without known sources—that is, no known links to other people with 

 no known history of health care in areas with 

, and no health care in international settings—making the detective work of tracking this elusive pathogen even more challenging. Like COVID-19, it spreads silently among asymptomatic patients, and so it can be very difficult to tell how it was first introduced to a particular region or community, and how many people have been affected.

This fungus has an uncanny ability to colonize the skin of medically fragile people

 in high-acuity long-term care facilities

—think ventilator-capable skilled nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). And those facilities have been the focus of media and public health attention.

s is not contained by hospital or facility walls and often spreads to and within facilities beyond LTACHs and vSNFs. Patients with chronic health care requirements often cycle between facilities of different acuities and end up in acute care hospitals when they decompensate clinically. In any of these facilities, 

can spread to other residents or patients when infection control procedures are not rigorously followed. If that resident or patient transfers to a new facility with inadequate infection control, the chain of transmission continues.

Skin colonization might not seem like a big deal since our skin is covered with a microbiome of yeasts and bacteria. However, 

 causes invasive infection (eg, sepsis, pneumonia) in a remarkable 5% to 10% of colonized residents and patients in long-term care, and 30% to 60% of those with invasive infections die within 30 days. Note that patients with these infections often have severe comorbidities, so some of this mortality is not attributable to 

 Early detection in health care facilities is essential to prevent spread of colonization and serious clinical infections from 

In addition to spreading easily between facilities

like any infectious disease, has no regard for state or jurisdictional borders and has continued to spread to new areas during the past 5 years. Health care facilities in the same geographic area (or even across the country) are highly interconnected, particularly in today’s landscape of frequent travel. At tertiary care hospitals that provide care for patients from multiple states, many patients are admitted from out of state or wish to transfer out of state to be closer to family. Patients are frequently transferred between facilities, taking familiar pathogens like methicillin-resistant 

 had not been identified before 2018, the focus at most local health departments had been on 

 screening strategies aimed at patients who received health care abroad. However, it has become clear that 

 has now firmly established its presence in multiple states, suggesting that we should strongly consider broadening our screening criteria to include these domestic, high-prevalence areas. Nowadays, the first introduction of 

 to a US region is more likely to come from a US patient without recent international travel.

Waiting on the first clinical case (eg, sepsis, pneumonia) to start a public health response is often too late. If 5% to 10% of patients colonized with 

 develop an invasive infection, then at least 10 to 20 patients are colonized with 

 before 1 person develops and tests positive for an invasive infection—and that infection may follow months or years after the patient first becomes colonized. In other words, 

 can spread widely across patients and facilities before the fungus finds its way into a person’s bloodstream and can certainly spread widely before it is detected by standard clinical laboratory surveillance measures.

Epidemiologic and Outbreak Investigation Experience

Through a novel partnership between local health departments and LTACHs, which began in 2018, a Southern California LTACH laboratory performed proactive species identification on any urine specimens that contained yeast to enable early identification of 

. Most yeast in urine (and other noninvasive) specimens normally reflects colonization instead of clinically significant infection, so species identification is not commonly performed by clinical labs. However, because 

 is a multidrug-resistant yeast of concern that can also be found in urine and other non-invasive specimens, species identification becomes a very helpful early-detection method.

Through this method, Southern California’s first 

 case was identified in Orange County 3 months before the first bloodstream infection was identified.

 Three months is, unfortunately, plenty of time for 

 to spread widely if prevention measures aren’t in place. Even with the early-detection process in Orange County, which prompted rapid, widespread colonization testing of patients in long-term care facilities through a partnership between CDC and local health departments, we identified more than 100 colonized people across the county that would otherwise have remained undetected.

 Had there been a 3-month delay, that number would have been much higher and transmission would have been much more difficult to contain through heightened infection control.

 is commonly found, how it can be detected, and how transmission occurs, pertinent strategies can be implemented. Early-detection strategies for 

include colonization screening for patients coming from high-risk long-term care facilities or areas known to have high 

 burden, point prevalence surveys (defined as colonization testing for all residents/patients) at high-risk long-term care facilities, and routine—or at least, more frequent—species identification of 

from all clinical specimens (eg, urine, sputum, wound, in addition to invasive specimens).

The action doesn’t stop there. Providing robust infection control across facilities makes a tremendous difference in slowing spread of 

 and other MDROs, specifically hand hygiene techniques, use of gowns and gloves when caring for patients with 

 and other patients with MDROs to prevent transmission, and rigorous environmental cleaning.

 Regular monitoring of these practices is important to ensure compliance.

The experience in Southern California had a few elements that were key to our success. For starters, it was a combined approach, with collaboration between CDC, state, and local health departments. The team built on existing infrastructure and relationships between local health departments and area vSNFs and LTACHs. And we acted early before 

had become a significant problem in the region.

Rather than just requesting that facilities screen for 

, CDC and health departments worked to make the process collaborative and demonstrate value for the facilities, including providing education about 

, expert feedback from trained infection preventionists, and long-term infection control support. This strengthened relationships and helped facility staff feel invested in case finding and screening for 

. It also fostered intercounty and interfacility cooperation on 

containment, making it a team effort. The team kept neighboring health departments in Southern California informed, recognizing that 

 could easily spread to facilities in nearby counties and trying to reduce the risk that stray embers would ignite transmission in those areas.

Finally, we worked closely with key laboratory partners from start to finish, including the Antibiotic Resistance Laboratory Network12 and the CDC laboratory to ensure we had resources to test screening specimens rapidly to allow for result-driven intervention.

The multidisciplinary nature of our intervention, offering education and support that facility staff valued, and interagency cooperation enabled quick and effective 

 detection and response in Southern California.

For regions seeking to join the mission to prevent 

 transmission, we’d recommend a similar proactive approach: promoting early awareness about 

, building relationships with local facilities, providing education and infection-control resources, and collaborating with neighboring regions to share strategies, lessons learned, and successes to strengthen detection and infection control in the region.

Our central message is that it’s important to identify the introduction of 

into a health care network as early as possible so that a public health response can be initiated to mitigate spread. Here is what facilities can do:

Be vigilant and proactive in identifying 

Ensure robust infection control at all times, not just after the first 

Enhance communication between facilities and health departments about patients’ MDROs status.

Provide high-quality, evidence-based care to all patients, regardless of MDRO status.

Given the substantial prevalence of MDROs in our health care networks, all facilities should commit to learning how to best care for patients colonized with MDROs. Most importantly, facilities would benefit from working together and not in a silo. Infection control across a health care network depends on the strength of infection control at each facility. A single case can easily multiply in a facility with poor infection control and then spread to other facilities. In addition, a facility with ongoing transmission can continue to seed the entire network if good detection methods and infection control are not present across all sites.

Local health departments play a critical role in raising awareness and providing education, support, and vigilance on emerging pathogens like 

 because their arrival may be just around the corner in this increasingly interconnected world. The most painful lesson in our experience was how quickly progress can stall if infection control falters or vigilance for 

 is lessened. The challenges during the COVID-19 pandemic, including widespread personal protective equipment and staffing constraints, prompted resurgence of 

in Southern California despite prior successful containment, as well as spread in other areas of the United States.

 underscored the need for ongoing support and consistent attention to rigorous infection control and early-detection strategies for pathogens of concern.

can be difficult to achieve, it is possible. With the right team, robust outreach, dedicated resources, good adherence to infection control measures, and coordinated collaboration, further transmission can be halted. Even better, investments in 

 detection infrastructure and control strategies in the present will help us in the future—not only for 

but also in preventing transmission of the next zebra pathogens on the horizon. 

Ellora Karmarkar, MD, MSc, is currently an infectious diseases (ID) fellow at the University of Washington and trained in internal medicine and pediatrics at the University of Chicago. She previously served as an epidemic intelligence service officer with the Centers for Disease Control and Prevention (2018-2020), and served as a medical officer in local public health for the COVID response until beginning ID fellowship.

Meghan Lyman, MD, is is a medical officer in the Mycotic Diseases Branch, Centers for Disease Control and Prevention. She began her career at CDC focusing on health care-associated infections and infection control, and is now leveraging that experience within the Mycotic Diseases Branch to prevent a wide range of fungal diseases.

Brendan R. Jackson, MD, MPH, leads CDC’s Mycotic Diseases Epidemiology Team, which is devoted to tracking and preventing a wide range of invasive fungal diseases, both established and emerging. He is a commander in the US Public Health Service.

. CDC.Updated October 27, 2021.Accessed November 16, 2021.

https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html

Lyman M, Forsberg K, Reuben J, et al. Notes from the field: transmission of pan-resistant and enchinocandin-resistant Candida auris in health care facilities - Texas and the District of Columbia, January-April 2021.

. 2021; 70(29):1022-1023. doi:10.15585/mmwr.mm7029a2

Forsberg K, Woodworth K, Walters M, et al. Candida auris: the recent emergence of a multidrug-resistant fungal pathogen. 

 biofilm colonization on skin niche conditions. 

. 2020;5(1):e00972-19. doi:10.1128/mSphere.00972-19

Jeffery-Smith A, Taori SK, Schelenz S, et al. Candida auris: a review of the literature. 

 2017;31(1):e00029-17. doi:10.1128/CMR.00029-17

Adams EH, Quinn M, Ostrowsky B, et al. The value added from 

 point prevalence and environmental studies in New York State. 

2018;5(suppl 1):S149. doi:10.1093/ofid/ofy210.396

Adams E, Quinn M, Tsay S, et al; Candida auris Investigation Workgroup. Candida auris in healthcare facilities, New York, USA, 2013-2017. 

. 2018;24(10):1816-1824. doi:10.3201/eid2410.180649

Kerins JL, Tang AS, Forsberg K, et al. Rapid emergence of 

. 2018;5(suppl 1):S28. doi:10.1093/ofid/ofy209.064

Southwick K, Adams EH, Greenko J, et al. New York State 2016-2018: progression from 

Contagion, December 2021 (Vol. 06, No. 6)

Case Study: Acute Coccidioidomycosis Acquired Crossing the US-Mexico Border

Identifying Disparities in Sepsis Diagnosis for Unbiased Care

Ready, Set, Cabenuva: Implementing Cabotegravir/Rilpivirine

Candida auris: Coming Soon to a Facility Near You?

Respiratory Virus Season: Colds and COVID-19 Update

Sticking It to COVID-19: The Expansion of the Pfizer-BioNTech Vaccine EUA

Is There a Better Choice Than TMP-SMX to Treat Stenotrophomonas maltophilia Infections?

Ibrexafungerp: Paving the Way for Novel Candida Pharmacotherapy

COVID-19: Year 2 in Review

Hope on the Horizon: Treatment for Carbapenem-Resistant Acinetobacter baumannii Infections

Latest News