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Accelerating Antimicrobial Stewardship Interventions Using the PhenoTest System for Gram-Negative Bacteremia: Data on Real-World Use

Along with a 1 reported case in Massachusetts, the

New Hampshire Department of Health and Human Services (DHHS) has confirmed a person infected with eastern equine encephalitis (EEE) has died. The public health agency said the person was hospitalized due to severe central nervous system disease. The last reported human EEEV infection in New Hampshire was in 2014, when DHHS identified 3 human infections, including 2 fatalities. In the same statement, DHHS mentions there has been 1 confirmed case in Vermont this summer.

On August 16, the Massachusetts Department of Public Health (MDPH) released a statement discussing the confirmation of the first human case of EEE in the state this year. The confirmed case was discovered in an 80 year old man who was exposed to the vector borne disease in Worcester County. As a result, the risk level in the local communities of Douglas, Oxford, Sutton, and Webster has been raised to critical, and in Dudley, Northbridge, and Uxbridge the risk is increased to high.

Additionally, the neighboring communities of Auburn, Charlton, Grafton, Leicester, Mendon, Millbury, Millville, Southbridge, and Upton are now considered at moderate risk according to MDPH.

“This is the first time we have seen a person infected with EEE in Massachusetts since 2020,” Public Health Commissioner Robbie Goldstein, MD, PhD, said in a statement. “EEE is a rare but serious disease and a public health concern. We want to remind residents of the need to protect themselves from mosquito bites, especially in areas of the state where we are seeing EEE activity.

Though very rare, EEE is serious and a potentially fatal disease that can affect people of all ages. EEE is generally spread to humans through the bite of an infected mosquito. There were 12 human cases of EEE in Massachusetts in 2019 with 6 deaths, and 5 human cases with 1 death in 2020. There were no human cases of EEE in Massachusetts in 2021, 2022, or 2023.

EEE has a fatality rate of 33% to 70%, with most deaths occurring 2–10 days after the onset of symptoms.

In addition to a high mortality rate, long-term physical and mental complications, including permanent neurological deficits have been identified in many people who survive EEE.

Plymouth is approximately 40 miles south of Boston along the coast, and Worcester County is in the middle of the state, so the 2 areas are not in close proximity, but due to the elevated risk locally, the town of Plymouth decided to take action in response to outdoor parks. As of last Friday, all town public parks and fields are close daily from dusk until dawn.

“As Mass DPH has now elevated Plymouth’s EEE risk status to high, it is important to take extra precautions when outdoors and follow state and local health guidelines to avoid unnecessary risk to exposure to EEE. The health and safety of our community, residents, and visitors remain our priority,” Plymouth’s Commissioner of Health and Human Services, Michelle Bratti, said in a statement.

According to the Centers for Disease Control and Prevention (CDC) most people who are infected with the virus do not develop symptoms; however, for those that do, the date from the bite to the onset of the illness is 4 to 10 days. EEE can also result in fever or neurologic disease. The type of illness will depend on the age of the person and other factors. Those who are infected can develop meningitis.

There are no FDA-approved treatments for EEE and for patients who develop severe cases, they can be hospitalized to receive supportive treatment.

Over the weekend, MDPH detailed plans of spraying for mosquitos including aerially in areas of Plymouth County, and truck-mounted spraying in parts of Worcester County. As of Saturday, 10 communities in Massachusetts were raised to high or critical risk for EEE virus.

“The risk from EEE is high in parts of Plymouth County and critical in parts of Worcester County,” State Epidemiologist Catherine M. Brown, DVM, said in a statement. “In addition to recommending that people use mosquito repellent with an EPA-registered active ingredient and clothing to reduce exposed skin, we also recommend that evening outdoor events be rescheduled to avoid the hours between dusk and dawn. The mosquitoes most likely to spread EEE are most active during the dusk to dawn hours.”

There are preventative strategies to avoid EEE, and the MDPH has listed such measures 

For those who live in Massachusetts and want more information on EEE, it can be found 

 or by calling the DPH Division of Epidemiology at 617-983-6800.

1.NH DHHS Identifies Person Infected with Eastern Equine Encephalitis Virus in New Hampshire.The New Hampshire Department of Health and Human Services. August 27, 2024. Accessed August 28, 2024.
https://www.dhhs.nh.gov/news-and-media/nh-dhhs-identifies-person-infected-eastern-equine-encephalitis-virus-new-hampshire
2. State health officials announce season’s first human case of Eastern Equine Encephalitis in Massachusetts. MDPH. August 16, 2024. Accessed August 27, 2024.
https://www.mass.gov/news/state-health-officials-announce-seasons-first-human-case-of-eastern-equine-encephalitis-in-massachusetts
3.Plymouth to Close all Public Parks and Fields from Dusk to Dawn. Town of Plymouth. August 23, 2024. Accessed August 27, 2024. PDF.
4. Eastern Equine Encephalitis: Symptoms, Diagnosis, and Treatment. CDC. May 15, 2024. Accessed August 27, 2024.
https://www.cdc.gov/eastern-equine-encephalitis/symptoms-diagnosis-treatment/index.html
5. State officials announce plans to spray for mosquitoes in sections of Worcester and Plymouth counties due to EEE. MDPH. August 24, 2024. Accessed August 27, 2024. 
https://www.mass.gov/news/state-officials-announce-plans-to-spray-for-mosquitoes-in-sections-of-worcester-and-plymouth-counties-due-to-eee



The town of Plymouth decided to prohibit people from using the parks from dusk to dawn due to concerns over eastern equine encephalitis after a man contracted the rare disease in the state.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

The country’s largest fecal distributor, OpenBiome, could be prevented from offering the product next year if the FDA does not approve the product 

Due to FDA Policy Change, Fecal Microbiota Transplants are in a Tenuous Position

This fall, there has been some legal limbo going on at the FDA as it pertains to deciding if the federal agency should restrict the nonprofit company, OpenBiome, from continuing to distribute its fecal products for use in fecal microbiota transplants (FMT). This procedure has been a life-saving treatment for both adult and pediatric patients suffering from fulminant 

Prior to this fall, the FDA had allowed the distribution of the company’s fecal products under enforcement discretion for many years.

 However, the FDA changed its position creating an uneasy, untenable position for the future of FMT—at least in the short term.

Without OpenBiome’s ability to distribute their product, many patients might not have immediate access to FMT, and this is not an ideal situation considering the severity of infection for patients with fulminant 

, including the possibility it could cause death.

However, OpenBiome and another stakeholder, the 

 patient advocacy organization, the Peggy Lillis Foundation (PLF), have both pointed out the FDA has been open in listening to the needs of 

 patients and the community in allowing for the fecal products to be distributed while they try to find a more permanent solution.

“We are thankful to the FDA for listening to the patient and clinician communities and prevailing evidence and making this decision to prioritize patient care. As part of this guidance, we are submitting an [investigational new drug] IND application to the FDA by November 30th,” OpenBiome wrote in a statement on their website.

Christian Lillis, the CEO of PLF, believes the FDA policy change was more about unexpected consequences, and that the federal agency did not foresee this issue arising.

"I really think that this was unintended, and I'm glad that they [the FDA] listened to us and have come up with—at least a solution in the interim—that we can hopefully work together,” said Lillis.

The FDA has extended the deadline for OpenBiome to continue distributing their product through the end of this year, while they prepare their IND application.

Beginning in September and lasting through the end of October, many were concerned that OpenBiome, the country’s largest distributor of fecal microbiota transplant (FMT) products might be forced to stop altogether.

OpenBiome noted that it was only going to continue offering the products through October 31 in light of the fact the federal government said it would need to review the IND.

To be clear, these traditional FMT differ from the newer 

 that have been FDA approved over the last 2 years. LBP have been indicated for patients with recurrent 

, and not the other aforementioned groups. These newer modalities have been shown to be efficacious and safe.

Lillis and PLF remain what he calls “treatment agnostic” to the existing modalities.

“We need to be clear from the jump that the Peggy Lillis Foundation doesn't endorse or recommend any particular treatment,” Lillis said. “That decision is best made between a patient and their doctor, but what we do want is as many options to treat this infection as possible. And that's why we also need to maintain access to traditional FMT and it's really for a particular subset of patients.”

References
1. Enforcement Discretion for Investigational FMT Extended for Severe and Fulminant CDI. Openbiome statement. Accessed November 13, 2024.
https://openbiome.org/fmt-distribution-through-december-31/

The country’s largest fecal distributor, OpenBiome, could be prevented from offering the product next year if the FDA does not approve the product used for fecal microbiota transplants  to treat fulminant C difficile.   

Due to FDA Policy Change, Fecal Microbiota Transplants Are in a Tenuous Position

Chad Costley, MD, MBA, provided an update on BlueWillow Biologics' NanoVax™ intranasal vaccine for H5N1, with Phase 1 trial data showing broad immune responses and no serious adverse events.

Rebuilding Trust in New Intranasal Vaccine for Avian Flu and Other Respiratory Diseases

At the World Vaccine Congress Europe, Chad Costley, MD, MBA, president and CEO of BlueWillow Biologics, presented an update on the company’s NanoVax intranasal adjuvant vaccine for avian flu (H5N1). In our interview, Costley discussed the vaccine's design, addressed concerns about safety and public hesitancy, and highlighted the study's potential.

The trial design simulated real-world infection and assessed how NanoVax™ primes the immune system. “With avian flu, we had a naive patient population who had not been exposed to the virus,” Costley explained. “We administered two intranasal doses of our adjuvanted recombinant protein vaccine followed by a third intramuscular dose.” He emphasized that the intramuscular dose, derived from an existing licensed H5 vaccine, was used as a “proxy for infection” to test how well the body would respond if it were exposed to the virus in the real world. “This approach helps us see whether our intranasal vaccine can prime the immune system to mount a robust, protective response upon real infection,” Costley added.

Vaccine hesitancy remains a challenge, especially in the context of COVID-19 and flu vaccines. Costley emphasized the potential for NanoVax™ to address these concerns, particularly for individuals who fear needles. “A significant portion of vaccine hesitancy is due to needle phobia,” said Costley, noting that intranasal vaccines, such as NanoVax™, can bypass this issue. “Any intranasal vaccine, including ours, can avoid the discomfort and reluctance that comes with needles.” He also noted that misinformation about vaccine safety remains a barrier.

Addressing safety concerns, Costley referenced Berna's historical issues with intranasal adjuvanted vaccines. This example of a 2000s-era flu vaccine that caused Bell’s Palsy in some recipients, led to widespread distrust of intranasal adjuvants. “We think our platform addresses those safety issues directly,” he explained. “We have a novel oil-and-water emulsion that prevents adjuvants from reaching the olfactory bulb in the nose, which could lead to neurological side effects.” BlueWillow’s clinical trials have shown no serious adverse events to date, strengthening the safety profile of NanoVax.

Costley also underscored the advantages of intranasal vaccination for respiratory diseases like influenza, pointing out that this method mimics the natural route of infection. “We don’t get infected through our arms, we get infected through our noses,” he explained. “An intranasal vaccine has the potential to prime the immune system at the site of infection, providing a more robust and natural response.”

NanoVax contrasts with most current intranasal vaccines, which rely on live attenuated viruses. While live virus vaccines like FluMist have benefits, they also carry risks. NanoVax uses a recombinant protein and adjuvant system, generating immunity without the risks associated with live viruses.

Costley emphasized that the goal of vaccination is not only to prevent illness but also to reduce viral transmission. “What we learned from COVID is that protection means more than just keeping people from getting sick. It also means reducing viral shedding and carriage, which are critical for controlling the spread of disease,” Costley said. He believes NanoVax has the potential to address both aspects, providing immunity against disease while also reducing the likelihood of contagion. “For respiratory diseases, that dual protection is absolutely critical.”

Although BlueWillow has not yet disclosed the full results of its H5N1 clinical trial, Costley shared that the Phase 1 trial exceeded expectations. “We’re very excited to report that through some additional funding, we’ve been able to expand the data set, which now includes not just mucosal antibodies but systemic responses, cellular responses, and ADCC (antibody-dependent cell-mediated cytotoxicity) responses,” he said. Costley expressed optimism that the full results will soon be made public, though additional weeks of analysis are required.

BlueWillow Biologics' NanoVax platform offers an intranasal alternative to injection-based vaccines and could reshape vaccine delivery. With trial results and a safety profile, it could play a key role in preventing disease and transmission as more data from its H5N1 trials are released.

BlueWillow Biologics to Present Significant Progress on Its Novel Intranasal Vaccine Technology at World Vaccine Congress Europe. 

October 28, 2024. Accessed November 12, 2024. https://www.biospace.com/press-releases/bluewillow-biologics-to-present-significant-progress-on-its-novel-intranasal-vaccine-technology-at-world-vaccine-congress-europe 

Chad Costley, MD, MBA, provided an update on BlueWillow Biologics' NanoVax intranasal vaccine for H5N1, with Phase 1 trial data showing broad immune responses and no serious adverse events.

Conferences

Rebuilding Trust in Intranasal Vaccines for Avian Flu and Other Respiratory Diseases

George Sakoulas, MD, provided commentary on challenging patients with comorbidities such as COPD, structural lung disease, asthma, and other health issues

Clinical Considerations for Treating Patients with Pneumonia 

As we are heading into seasonal respiratory virus season, what are you seeing in your own practice and region of the country in this regard, and how should clinicians be preparing to combat a resurgence in COVID 19 and the early onset of respiratory season?

I'm based in Southern California, working as an ID physician. What we're noticing here is a slight uptick in flu cases. In fact, as of this time of year, we're seeing about three times more flu cases than we had at the same point last year. This suggests we might be in for a heavier flu season than usual, at least based on early indicators. Typically, our flu season peaks in January. In Southern California, it's quite predictable—flu activity often surges right after the holiday season. People travel, visit family, return home, and then around January 5th, it's as if a fire is lit.

We also had a COVID bump in August, which mirrored trends across much of the country, though it was far less severe than what we saw during the pandemic years. We had some hospitalizations, but most were incidental.

For clinicians, the main preparation is staying informed and encouraging patient vaccination. We now have vaccines for influenza, COVID, and RSV. RSV vaccines are recommended for anyone over 60 or for anyone at high risk over 75. Encouraging vaccination is really the most effective tool we have since the therapeutic options for viral infections are limited. Although some treatments show statistically significant effects in studies, the clinical impact often seems minor.

In short, with viral infections, prevention through vaccination is key. We as healthcare providers are mandated to get vaccinated, and ideally, the best time to do so is now.



For pneumonia patients with lung function related comorbidities—such as COPD or structural lung disease, smokers, over age 65, asthma—who are these most challenging patients and why?

 Older patients present unique challenges, especially those with structural lung disease. Anytime there’s an infection or problem in the lungs, entering that illness with a compromised organ system makes it significantly more challenging. This is mainly because they have limited respiratory reserve. When someone with underlying health issues gets an illness, even a minor one, it can affect them much more severely than a healthier person. Additionally, these patients often receive frequent antibiotic treatments due to repeated exacerbations and ongoing care needs. Frequent antibiotic use increases the risk of antibiotic resistance, which, in turn, makes them more susceptible to infections by unusual organisms that are less common in straightforward cases of community-acquired pneumonia.

 What are the clinical considerations you are thinking about in your treatment management?

 When it comes to pneumonia—and, really, most infections—it often comes down to two main factors: comorbidities and severity of illness. Stopping an infection is a bit like stopping a car. Your level of sickness can be thought of as your speed, while your comorbidities are like the type of surface you're on. If you have multiple comorbidities, it’s like driving on an icy downhill road; if you're very sick, it’s as if you're moving at a high speed. These are the two factors I explain to patients and students when discussing how we assess infection risks and make treatment decisions.

For example, if a patient has multiple comorbidities or has been on prior antibiotics, we need to make specific treatment decisions. However, if a younger patient with no major risk factors becomes severely ill—such as requiring ICU admission or ventilation within the first 24 to 48 hours of hospitalization—I start to consider staph pneumonia, particularly during the respiratory season we discussed earlier.



The conversation was edited for grammar and clarity. 

George Sakoulas, MD, provided commentary on challenging patients with comorbidities such as COPD, structural lung disease, asthma, and other health issues.


Mixed fungal brain abscess identified by broadrange fungal polymerase chain reaction (PCR) as Rhizopus oryzae complex and Aspergillus spp in a person with newly diagnosed HIV who injects drugs 


A cisgender male aged 29 years with substance use disorder including injection drug use, as well as opioid use disorder and marginal housing, initially was admitted after being found lying in the street, covered in feces, and unresponsive. There were no next of kin or other persons to corroborate recent events. When evaluated upon arrival at the hospital, the patient’s mental status was altered and he was unable to contribute to history of present illness. 


The patient’s history was notable for substance use disorder with injection drug use; infective endocarditis was listed in his chart as a previous diagnosis without further details available. 

 
The patient was known to our health care system to have used drugs recently, but the exact techniques by which he used, how often, and the locations were unknown at the time of our evaluation. The patient was known to be homeless and living on the street. 


On admission, the patient was generally ill appearing, unkempt, and not in acute distress. He had a fever with maximum temperature of 101.3° F. His heart rate was 54 beats per minute, blood pressure was 129/93 mm Hg, respiration rate was 16 breaths per minute, and oxygen saturation level was 96% on room air. There was temporal wasting. There was no nuchal rigidity. There was no heart murmur appreciated. There were no wheezes or crackles on pulmonary examination. There were no obvious signs of ongoing injection drug use, and no evidence of skin infections was noted. On initial neurologic examination, the patient was lethargic and opened his eyes to verbal stimuli but was not following commands otherwise. He was not verbal, had symmetric facial expressions, and withdrew extremities to noxious stimuli.

 
Relevant positive laboratory findings early in the patient’s hospital course included a new positive HIV 1/2 antigen/antibody fourth-generation assay with a CD4 cell count of 226 (normal range, 410-1590 ABS cell/μL) and a viral load of 502,000 copies/ mL. A urine toxicology on admission yielded positive results for fentanyl and amphetamine. A CT of the head on day 1 of hospitalization did not show any acute intracranial abnormalities. An MRI of the brain on day 3 revealed acute to subacute left basal ganglia infarcts with mild peripheral enhancement to suggest an infectious or neoplastic process (

A CT of the head on day 4 showed findings consistent with hemorrhagic conversion of the previously noted left basal ganglia infarct. A cerebrospinal fluid analysis on day 10 had 1390 red blood cells/uL and 240 white blood cells/uL (normal range, 0-5 cells/uL) with 78% lymphocytes, 13% neutrophils, 8% macrophages, and 1% basophils. There was elevated cerebrospinal fluid protein at 128 mg/ dL (normal range, 0-45 mg/dL) and glucose of 39 mg/dL (normal range, 40-70 mg/dL). Blood culture results were negative. 

Transthoracic and transesophageal echocardiography studies were negative for vegetations. Other pertinent negative laboratory results included cerebrospinal fluid Gram stain and cultures including bacterial, fungal, and acid fast; the meningoencephalitis BioFire panel; cerebrospinal fluid and serum cryptococcal antigen; cerebrospinal fluid and serum JC polyoma virus PCR; serum Toxoplasma gondii antibodies; cerebrospinal fluid Toxoplasma gondii PCR; cerebrospinal fluid cytology and flow cytometry; and Treponema pallidum antibody cascade screening assay. 




On initial presentation to another hospital, the patient was started on empiric coverage with ceftriaxone and vancomycin. He decompensated from a neurologic perspective and developed new right-sided weakness with worsening mental status on day 3 of hospitalization, requiring intubation and intensive unit–level care. With his acute neurologic decompensation, he was broadened to meningoencephalitis coverage with the addition of acyclovir dosed for central nervous system penetration. 

At this time, an MRI of the brain and CT of the head were ordered, with both showing a new left-sided basal ganglia infarct. He also had a seizure-like episode. On repeat CT on day 8 of hospitalization, a new right-sided basal ganglia infarct was seen. The patient underwent lumbar puncture on day 10. That day, ampicillin was added to the ceftriaxone and vancomycin, and acyclovir was discontinued. Initial microbiologic work-up was unrevealing. He was able to be extubated, but his neurologic status remained poor. Although results for Toxoplasma gondii antibodies were negative and CD4 cell count was greater than 200, on day 15 of hospitalization, the patient was started on empiric toxoplasmosis treatment with clindamycin, pyrimethamine, and leucovorin. He was transferred to our quaternary care center on day 21 for consideration of brain biopsy and for seizure management. No seizures were clinically captured. The neurosurgery department requested a repeat MRI of the brain while the patient was on treatment for toxoplasmosis to assess the need for biopsy.

On day 18, antibiotics were stopped except for clindamycin, pyrimethamine, and leucovorin for toxoplasmosis. On day 22, he was switched to sulfamethoxazole-trimethoprim alone and MRI of the brain was repeated, revealing extensive signal abnormality in the left more than the right basal ganglia with associated edema and mass effect, including a lesion centered in the left basal ganglia measuring 3.4 × 2.3 cm transaxially (

). Multiple attempts were made to repeat MRIs while treating for presumed toxoplasmosis, but imaging was limited due to patient movement. He was intubated for a repeat MRI on day 29 of hospitalization, which showed hemorrhagic, peripherally enhancing nonpyogenic lesions in both gangliocapsular regions extending into the left cerebral peduncle/midbrain with surrounding edema. In addition to the initial 3.4 × 2.3-cm lesion previously noted, there was a 1.0 × 1.0-cm lesion described in the left cerebral peduncle on this MRI. 


Given progressive disease seen on MRI, the patient was taken for a stereotactic brain biopsy on day 31 of hospitalization. A 1-cm soft tissue section was sent to frozen pathology, which revealed fungal hyphae with a surrounding inflammatory infiltrate, for which we started the patient on empiric liposomal amphotericin B intravenously. Results from Gram stain and cultures for bacterial, fungal, and acid-fast organisms were negative. The histopathology showed fungal organisms with broad pleomorphic hyphae. On review with the pathologist, there were elements of both Aspergillus and mucormycosis present (

). Broad-range PCR was performed on paraffin-embedded tissue to send out to the University of Washington, and 28S ribosomal DNA amplification showed presence of 2 fungal species: Rhizopus oryzae complex and Aspergillus spp related to Aspergillus magnivesiculatus. 

 
On day 31 of hospitalization, after the frozen pathology returned from the brain biopsy, the patient was started on high-dose liposomal amphotericin B at 10 mg/kg intravenously every 24 hours and toxoplasmosis treatment was discontinued. He tolerated liposomal amphotericin B treatment for 3 weeks but developed refractory hypokalemia that required a transition to isavuconazonium sulfate intravenously and later orally via a percutaneous gastrostomy tube. The neurosurgery department did not recommend abscess debridement given location within the basal ganglia and high morbidity associated with surgery. 

Additionally, he was started on antiretrovirals for HIV with emtricitabine, tenofovir disoproxil fumarate, and dolutegravir after 16 days of antifungal therapy and serial follow-up MRI of the brain showed continuous decrease in size in his central nervous system lesions. One year after his initial presentation, an MRI of the brain showed a remaining 1.3 × 0.5-mm left thalamocapsular abscess and a 0.5 × 0.3-cm left cerebral peduncle abscess. He remains on isavuconazonium for at least 18 to 24 months with final duration dependent on follow-up imaging and clinical course.

 
This individual presented with a mixed fungal infection, centered in the basal ganglia, in the setting of injection drug use and newly diagnosed HIV/AIDS. Per meta-analysis from Brouwer et al, fungi comprise only 1% of brain abscesses and the basal ganglia accounts for approximately 3% of brain abscesses.

 Rhizopus oryzae is responsible for 70% of all cases of mucormycosis.

 In individuals who inject drugs, the organism is inoculated directly into the bloodstream, where it frequently involves the basal ganglia, which may be due to the tissue’s high iron content and Rhizopus spp spores requiring free iron to grow.

A systematic review of mucormycosis in patients living with HIV indicated that individuals who inject drugs were more likely to develop isolated cerebral mucormycosis than those who do not inject drugs.

 The same review found that other copathogens were present in more than half of cases.

 In our case, presumably, the Aspergillus was injected at the same time as the Rhizopus. Aspergillus has also been described in the literature as a pathogen that has a predilection for infecting the basal ganglia.

Fungi with branching hyphae, such as Mucor and Aspergillus, have angioinvasive qualities that can lead to luminal obstruction of small blood vessels, causing intravascular thrombosis, infarction, and further abscess development.

For brain lesions identified on imaging of persons living with HIV (PLWH), other pathologies such as toxoplasmosis, lymphoma, and cryptococcosis should be considered.

 However, perhaps an even broader differential should be maintained in PLWH who have other risk factors such as injection drug use, and should include opportunistic fungal infections. During broad-range PCR testing, the genes are amplified and sequenced, and the resulting data are subsequently compared against established databases to ascertain the identity of an organism.

 The specific targets used for comparison vary depending on the type of organism under analysis.

 Broad-range PCR testing can be particularly useful when cultures or pathology results are negative or inconclusive but suspicion of an infection is high. It can also be helpful if the histopathology identifies an unexpected result and further evidence is needed to support a diagnosis and, ultimately, help guide a treatment plan.

 Fungi contain highly conserved ribosomal subunits, including 18S and 28S.

Between coding regions of 18S and 28S ribosomal RNA, there are internal transcribed spacer regions that contain variability among fungal species and can be amplified by PCR to identify specific fungal species.

 For our patient, broad-range PCR testing proved critical in establishing a diagnosis; 2 fungal morphologies were seen on histopathology, biopsy culture results were negative, and antimicrobial therapy was the mainstay of management with no further surgical intervention planned given a high-risk location within the basal ganglia.

Brouwer MC, Coutinho JM, van de Beek D. Clinical characteristics and outcome of brain abscess: systematic review and meta-analysis. 

. 2014;82(9):806-813. doi:10.1212/WNL.0000000000000172

Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. 

. 2012;54 suppl 1(suppl 1):S16-S22. doi:10.1093/cid/cir865

Stave GM, Heimberger T, Kerkering TM. Zygomycosis of the basal ganglia in intravenous drug users. 

. 1989;86(1):115-117. doi:10.1016/0002-9343(89)90242-8

Meyerowitz EA, Sanchez S, Mansour MK, Triant VA, Goldberg MB. Isolated cerebral mucormycosis in immunocompetent adults who inject drugs: case reports and systematic review of the literature. 

. 2020;7(12):ofaa552. doi:10.1093/ofid/ofaa552

Moreira J, Varon A, Galhardo MC, et al. The burden of mucormycosis in HIV-infected patients: a systematic review. 

. 2016;73(3):181-188. doi:10.1016/j.jinf.2016.06.013

Hadley C, Haneef Mohamed AW, Singhal A. Central nervous system fungal infection in a young male with a history of intravenous drug abuse and hepatitis C. 

. 2017;12(3):590-596. doi:10.1016/j.radcr.2017.03.016

Clinicians review a patient case including diagnosis, treatment, and follow-up.

Monica V. Mahoney, PharmD, BCPS (AQID), BCIDP

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