John Parkinson

A female patient in her mid 70s is admitted to a local hospital after presenting with shortness of breath and cognitive impairment that includes confusion. She has existing comorbidities that include edema and COPD after a long history of smoking.

A chest x-ray diagnoses the patient with pneumonia. And after a blood test, it’s confirmed the patient has bacterial pneumonia, but the precise organism is not determined. Because of the limited knowledge of the exact bacterium, the patient’s clinician treats her with broad spectrum antibiotics because of concerns related to multidrug resistant organisms such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA).

The patient’s condition quickly worsens, and she falls into unconsciousness. She is placed on artificial breathing apparatus, and her family is called as the clinician treating her believes she may expire if she does not improve.

This becomes a wait-and-see situation with the family in limbo awaiting a potential worse-case scenario.

Fortunately, the antibiotics begin to take effect and the patient recovers, but not after the patient and her family have gone through a harrowing experience. Someday, possibly in the near future, patients may not need to go through this care scenario as clinicians may have the ability to identify the exact bacterium and prescribe the proper antibiotics—all in a shorter time.

In the aforementioned case, which continues to happen across the US health care system, clinicians are limited by the types of testing available and guidelines on how they treat. They treat broadly with antibiotics, and hope for the best possible outcomes.

The community hospital where the patient was treated had limited laboratory testing capabilities. The good news is diagnostic technologies are evolving, and lab panels have improved dramatically. These panels offer specificity and speed that can identify the bacteria quickly and reduce the time to optimal therapy (TTOT), thus leading to potentially more optimal treatment outcomes.

One example has been the development of multiplex polymerase chain reaction (PCR) panels that can be used to identify the rapid detection of pathogens in blood cultures, cerebrospinal fluid stool, and respiratory tract specimens.

Adoption of rapid PCR panels for positive blood cultures has been growing, and antimicrobial stewardship programs at many institutions perform audit and feedback based upon the results of such panels as a basis for interventions.

And the proliferation of these panels has helped to grow out the concept of diagnostic stewardship. This novel concept creates an emphasis to streamline the diagnosis process and get to TTOT more quickly. According to the CDC, “Diagnostic stewardship is defined as ordering the right tests for the right patient at the right time to inform and optimize patient care.”



Although these new rapid diagnostics enable specificity and speed, the challenges to widespread usage remain expense and availability. And even for those hospitals that can access such panels, it remains a priority to use them judiciously.

Lab Perspective: Who Will Run the Tests and Interpret Results?

Much like everything else in medicine, the laboratory is another field that is evolving. With these emerging rapid diagnostics comes the increased need to have more laboratory professionals run and interpret results of complex tests.And yet, labs have seen a series of challenges including more testing due to COVID-19—leading to burnout and staffing shortages.

“We've had these staffing issues for many years prior to the pandemic,” explained Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc, university distinguished professor and chair of the Clinical Laboratory Science Program in the College of Health Professions at Texas State University where he also serves as the associate director of the Translational Health Research Center. “The pandemic has exacerbated these issues.”

Rohde remains in touch with many of his former students and says the pandemic has made for an interesting situation for lab professionals by increasing their value. It has created a hired gun atmosphere for experienced personnel where they are getting recruited to work with different institutions and leaving behind inexperienced lab technicians in their existing institutions.

“We're seeing some vacuums in trauma centers and major hospitals where now you don't have a mix of seasoned veterans and rookies,” Rohde explained. “I've talked with different people who are a little bit in panic mode, where they'll have one person, for example, working a night shift at a middle-of-the-road hospital that has some trauma issues in the middle of the night or during the day and the lab professional is left alone. And while we value every single medical lab scientist that we educate, we all know that on-the-job experiences, dealing with crises, and complex decision making should happen in the realm of seasoned veterans being around.”

Within the challenge remains the ability to determine and process so many tests, and this is where the rubber meets the road for diagnostic stewardship to go from novel concept to widespread reality.

Rohde points to education and the lab’s collaboration with clinicians as being potential strategies to aid in determining what tests are necessary. On the education side, he points to the new doctorate of clinical laboratory sciences (DCLS) degree, which is at three major universities. Rohde says lab professionals who have a few years experience may want to get their doctorate. 

With PhDs in hand, lab scientists can get more involved on the clinical side, especially as it pertains to testing.

“Those individuals will be rounding with physicians from a laboratory medicine standpoint, they'll be interacting with nurses, pharmacists, and the team in a way to help educate and inform proper and accurate test selection, ie stewardship, versus bartering every test, or ordering the same test over and over day after day when you may only need it once every five days,” Rohde stated.

Clinician Perspective: Solving the Testing Expense Issue

Although the advent of rapid diagnostics is a very needed addition, there remains the expense behind ordering these panels. And testing guidelines have not caught up to the new diagnostic technologies in determining who needs such tests.

As such, treatment guidelines are done on an institution by institution basis. One potential strategy to help in this area is using a combination of predictive tools and guidelines to help decide when rapid diagnostics are needed.

For example, clinicians have used the Drug Resistance in Pneumonia (DRIP) tool to aid in predicting cases of bacterial pneumonia that prove resistant to antibiotics. It can, however, still lead to some use of broad-spectrum antibiotics and over coverage.

Matthew Sims, MD, PhD, director of Infectious Disease Research, Corewell Health East, is a proponent of using the established DRIP in concert with rapid diagnostics. Sims and his team have done a lot of research using the rapid diagnostic the Unyvero Lower Respiratory Tract Panel (LRTP) and aided in obtaining its FDA approval.

In his research, he decided to study combining the two tools to see if they could improve diagnosis and tailor antibiotic treatment by creating an algorithm.

“Using an existing patient pool from a clinical trial of the LRTP, a DRIP score was determined for each patient. When data elements of the DRIP score were unavailable a DRIPmax and DRIPmin were calculated assuming all missing elements were positive or negative respectively,” Sims and his coinvestigator wrote about their methods. “The sensitivity and specificity of the DRIP score vs culture and LRTP were determined. An algorithm for antibiotic selection based on the results of the DRIP score combined with the LRTP was applied to each patient.”

This combination helped in finding patients who were susceptible to drug resistance.

“What we found is that if you use just the DRIP score as your initial cut and we’re going to run the [LRTP] panel on patients who have a score of four or more—which is the cutoff—you catch almost everyone who has a drug-resistant pathogen,” Sims stated.

Sims and his coinvestigator, medical student Richard Ramirez, developed their study’s results into a subsequent poster, “Combining DRIP Score and Rapid Diagnostics for Improved Antibiotic Stewardship,” which Sims presented at the infectious disease conference, ID Week 2022 in October.

Ultimately, the ability to bore down on diagnosis and timely, proper treatment is critical, especially in severe medical cases. And although the near term is undetermined in how to resolve these cost and guideline issues, innovation rules the day and modern medicine will find solutions to fix the problem.

“It's not something you can implement overnight, but we are seeing absolute payoff with our DCLS graduates that are aligning with healthcare systems and hospitals, not only in life and quality of patient care, but in actual dollars saved,” Rohde said. “If you don't order all of these tests, especially some of these expensive molecular assays, you can actually help the bottom line of a hospital and a medical lab. It's part of the ongoing conversation alongside other things to be more accurate, and quicker turnarounds—and all of those things that we need to do to improve patient care.” 

1. Miller M, et al. Early experience with the BioFire pneumonia panel. Contagion. 2020;05 (05): 16-17.

2. Banerjee R, Teng CB, Cunningham SA, et al. Randomized trial of rapid multiplex polymerase chain reaction-based blood culture identification and susceptibility testing. Clin Infect Dis. 2015;61(7):1071-1080. doi:10.1093/cid/civ447

3. Current Stewardship Report. Centers for Disease Control and Prevention. Last reviewed October 6, 2022. Accessed December 20, 2022. https://www.cdc.gov/antibiotic-use/stewardship-report/current.html

Articles

This novel concept can benefit patients and clinicians alike by appropriately applying new technologies to identify bacteria more efficiently and decrease the time to optimal therapy.

Diagnostic Stewardship: An Emerging Component With Far-Reaching Treatment Implications

Recently, the monkeypox incidence rates have greatly increased, prompting both the 

 to declare health emergencies for the virus. The former just declared in recent days, and allows for optimal mobilization of funding and resources to address the virus.

In July, the WHO stated the disease was a Public Health Emergency of International Concern (PHEIC). At that time, monkeypox infections have been reported in 68 countries where the virus is not endemic. Globally, there were just under 17,000 confirmed monkeypox infections.

The Centers for Disease Control and Prevention (CDC) discussed prioritizing specific high-risk groups for monkeypox clinical care and education in its latest Morbidity and Mortality Weekly Report (MMWR).

“Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, address equity, and minimize stigma, while maintaining vigilance for transmission in other populations,” MMWR reported. “Clinicians should test persons with rash consistent with monkeypox, regardless of whether the rash is disseminated or was preceded by prodrome.”

In the US, 2891 cases were reported from May-July 2022, in 43 states, Puerto Rico, and the District of Columbia. CDC received case report forms for 1195 (41%) cases as of July 27.

Among the report forms, the confirmed cases in the United States occurred in 99% of men, and “94% of whom reported recent male-to-male sexual or close intimate contact.”

Racial and minority groups are being disproportionately affected, as noticed by the report.

“Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons.”

And the presentations are atypical with fewer persons experiencing prodrome and more experiencing genital rashes.

The WHO has been involved in both smallpox and monkeypox health campaigns and reported in May the vaccines developed for the former also protect against the latter.

“Vaccines used during the smallpox eradication program also provided protection against monkeypox. Newer vaccines have been developed of which one has been approved for prevention of monkeypox,” WHO wrote in a statement.

WHO is recommending people in high-risk groups—including men who have sex with men and health care workers—get vaccinated.

In the US, states have had a limited vaccine supply. Vaccines are only being provided for people who are close contacts of those with confirmed cases.

And with the recent increase in demand, there may be some shortages in some areas in the US. For example, The San Francisco Department of Public Health (SFDPH) initially requested 35,000 doses of the monkeypox vaccine, and within the last week, San Francisco had only received approximately 12,000 doses.

CDC and the Food and Drug Administration (FDA) have developed a process to help clinicians secure an antiviral therapy, tecovirimat (Tpoxx), for monkeypox treatment. This falls under the expanded access investigational new drug (EA-IND). Clinicians can begin the process to secure tecovirimat by going 

Tecovirimat is manufactured by SIGA Technologies, and is approved for smallpox and is being studied for monkeypox treatment. 

spoke with SIGA Technologies Chief Scientific Officer Dennis Hruby, PhD,

Latest monkeypox updates from CDC and WHO.

Latest Monkeypox Trends, Vaccines and Public Health Policy by CDC, WHO

This interview article was originally published on 

Madeline Belk, PharmD, said that her institution, Huntsville Hospital in Huntsville, Alabama, has restricted prescribing privileges of fidaxomicin to the infectious disease (ID) and gastrointestinal (GI) providers only. 

 now recommending fidaxomicin for first-line therapy, Belk, and a team of investigators evaluated patients hospitalized with 

 who received treatment with oral vancomycin to determine outcomes and if they needed to shift to prescribing fidaxomicin. 

They performed a retrospective cohort study with adult patients hospitalized for CDI and who received vancomycin. These patients were analyzed between January 2020-December 2020 and were excluded if they received additional CDI therapies or were receiving treatment prior to hospitalization.

“One-hundred and eighteen patients were included in the analysis. On average, patients were 66 years old, most were female (58%), hospital length of stay was 12 days, most had CDI severity of mild-moderate or severe, and average duration of treatment was 14 days,” the investigators wrote. 

“Only 3 of 118 (2.5%) experienced recurrent CDI at 60 days. Thirty-day readmissions occurred in 23 (19%) of patients with only 3 (3%) deemed to be related to CDI. Variables associated with increased likelihood of 30-day readmission included age 65 and older (OR 4.53, 95% CI 1.12–18.37; p=0.034) and higher CCI score (OR 1.40, 95% CI 1.04–1.89; p=0.025).”

The investigators concluded that using oral vancomycin as a first-line therapy had low rates of recurrence and CDI-related readmissions, and they decided to keep fidaxomicin with the GI and ID providers.

The study, “Characteristics of patients hospitalized with Clostridioides difficile infection and treated with vancomycin,” was presented at the 

24th Annual Making a Difference in Infectious Disease (MAD-ID) Meeting 2022

 spoke to study coauthor Belk at the MAD-ID meeting who provided more information about the study’s findings.

Videos

With limitations on fidaxomicin at their facility, a hospital looked at vancomycin usage to determine if they needed to align with the new IDSA/SHEA CDI treatment guideline.

Madeline Belk, PharmD, Discusses Oral Vancomycin as a First-Line CDI Therapy

This article was originally published on our sister publication 

The latest update from the Centers for Disease Control and Prevention (CDC) said there was 1 confirmed case of monkeypox in Massachusetts, 6 cases of orthopox including the following states: 1 in New York, 1 in Washington, 2 in Florida and 2 in Utah. 

 has been observed in a few countires in Europe, in addition to the case in Massachusetts, which 

 a case in Portugal, according to the CDC.

One vaccine has been approved for prevention of monkeypox. The US does have a stockpile of available monkeypox vaccines. And for those who have had smallpox vaccines these can provide protection against monkeypox as well.

In a recent statement, CDC said it was tracking clusters of monkeypox in countries that do not normally report the virus. Although the agency is not clear how people in those clusters were exposed to the virus, cases have included people who self-identify as men who have sex with men.

The CDC said it's urging US providers to be alert for patients who have rash illnesses 

, regardless of whether they have traveled or have other specific risk factors for monkeypox.

“Many of these global reports of monkeypox cases are occurring within sexual networks. However, healthcare providers should be alert to any rash that has features typical of monkeypox. We’re asking the public to contact their healthcare provider if they have a new rash and are concerned about monkeypox,” said Inger Damon, MD, PhD, director of CDC’s Division of High-Consequence Pathogens and Pathology, where the agency’s poxvirus research is based.

The monkeypox virus is an enveloped double-stranded DNA virus that belongs to the 

 family. Outside labs can test for the orthopox virus and monkeypox diagnosis is confirmed at the CDC's facility.

The viral zoonotic disease occurs primarily in tropical rainforest areas of central and west Africa is occasionally exported to other regions. Last year, the United States had 2 confirmed cases in the US with travelers coming from West Africa.

The World Health Organization (WHO) reported that there have been 200 confirmed or suspected cases of monkeypox worldwide. Mostly in non-endemic countries. The current monkeypox circulating in Europe is reported to be mild and has a fatality rate of less than 1%. Most cases are expected to resolve within 2-4 weeks.

As this is an evolving story, check back on 

New information suggests a few more cases have surfaced in the United States, pending CDC confirmation.