C Difficile: A Landscape of Proactive & Reactive Treatment
DECEMBER 17, 2018
Prevention as the Best Medicine
Prevention has taken center stage when it comes to physicians’ primary treatment focus, and treatments for C difficile are no exception. In 2018, preventative treatment dominated the disease’s landscape, highlighting the increasing emphasis of containing and quelling the highly infectious bacteria.
As hospital environments and nursing staff have some of the highest transmission rates of the disease at 40%, Anna K. Barker, PhD, told MD Magazine® that controlling environmental factors may be most helpful when inhibiting disease transmission.
“The rate of hospital-acquired C difficile infection can be reduced dramatically by focusing on just 2 high-yield strategies—daily cleaning and asymptomatic screening at admission,” she said.
In a study led by Barker and fellow investigators from University of Wisconsin-Madison, the team found that after the implementation of enhanced and ideal levels of 6 observed interventions—daily and terminal cleaning, health care worker hand hygiene, patient hand hygiene, screening at admission, and patient transfer reduction—hospital-onset colonization and infection of the disease was further prevented.
Specifically, daily cleaning with a sporicidal disinfectant reduced hospital-onset infection by 2.48 cases per 10,000 patient-days while symptomatic screening reduced infection cases by 5.13 cases per 10,000 patient-days. Together, these correspond to 68.9% and 35.7% reductions in hospital-onset infection.
New innovations in hygienic prevention also took root in the form of new devices, such as the launderable mattress barrier.
Inventor of the cover, Edmond Hooker, DrPH, professor Xavier University, tested the device’s efficacy in an acute care hospital in Kentucky. During the pre- and post-periods of implementing the mattress cover, the average monthly count of hospital-onset C difficile infection was 1.79 (SD 1.51) and 1.03 (SD .96), respectively. During the pre- and post-periods, the corresponding average monthly rate (per 10,000 patient-days) was 7.94 (SD 6.30) and 4.71 (SD 4.42).
In the first model of the study, the bed barrier was associated with a 59% (95% CI 36-96%, P = .034) reduction, while the bed barrier was associated with a 59% (95% CI 36-99%, P< .05) reduction in the hospital-onset C difficile infection in the fully saturated mode.
“[The cover] basically allows the hospitals to do a couple of things,” Hooker told MD Mag®. “Even though you pay for the cover and have to launder the cover, it ends up being cheaper because you prevent a lot of infections, and you get the bedrooms turned over quicker.”
Honed devices and hygienic regimens were not the only preventative measures that emerged in 2018 though. Potential for a C difficile vaccine was also announced in Pfizer’s phase 3 clinical trial.
“The way the vaccine would help to prevent [C difficile] is if you find that optimum medium where you have the least amount of risk closer to that time that you need the vaccine,” Catia Mato Ferreira, PhD, global medical lead of Medical Affairs at Pfizer, told MD Mag®.
Ferreira explained that since individuals aged 50 years and older have a higher risk of developing the disease, it is important to vaccinate them ahead of that time. She added that the vaccine would aim to not only assist in preventing the disease, but also in fighting the toxins that cause the inflammation that leads to some of the more catastrophic events related to C difficile, such as colon damage and mortality.
While a vaccine would not replace other preventative measures like hand washing, it would provide another layer of protection and possibly lower the 29,000 C-difficile-related deaths recorded every year.
However, with the plethora of preventative treatments emerging for C difficile, of course differing opinions arise. Specifically, physicians differ on their opinions regarding the appropriate procedures for containing the bacteria in already infected patients.
According to Nicola Petrosillo, MD, how long a patient should be isolated in contact isolation after the end of diarrhea and the screening of asymptomatic carriers are 2 points of high controversy among physicians.
Regarding the first controversy, Petrosillo explained that while the guidelines recommend 48 hours of contact isolation, the bacteria spores can survive up to 4 weeks after the end of diarrhea.
“I think that we should consider this measure of 48 hours as very flexible, depending on the setting and patient being treated,” Petrosillo told MD Mag®. “In some cases, we should [consider] contact isolation for the [entire] stay in the hospital.”
Regarding the second controversy, Petrosillo explained that while the guidelines indicate that asymptomatic carriers should be screened, some studies indicate particular settings should make screening a priority.
“There are several studies that indicated that in a particular setting where there were immunocompromised patients like bone marrow transplant patients or elderly people in long-term care facilities, screening of asymptomatic carriers was effective in reducing the rate of C difficile infection in particular conditions, [such as] in outbreak settings and patients with high risk for C difficile infection,” Petrosillo said.
Still, additional emerging therapies for preventing C difficile infection continue to develop, such as beta-Lactamase, probiotics, vaccines, and lactoferrin therapy.
A Novel Treatment & Emerging Studies
While preventative treatments dominated the field in C difficile infections in 2018, reactive treatments didn’t lack in strides.
Only 26 days after the start of the new year, the US Food and Drug Administration (FDA) approved CutisPharma’s vancomycin hydrochloride (Firvanq) for the treatment of C-difficile-associated diarrhea and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains.
The approval also served as the first and only FDA-approved vancomycin oral liquid treatment option for C difficile infection.
Emphasizing the importance of the vancomycin approval, Dale N. Gerding, MD, told MD Mag®, “It’s very significant. Right now, I think it is probably the best drug that we have for C difficile, in terms of both cure and reduced recurrence.”
In a subset of young phase 2 clinical trial participants assessing the optimal treatment dose, investigators also created an algorithm that showed if a patient did not exhibit marked improvement after 3 days on 250 mg oral vancomycin, a dosage upped to 500 mg oral vancomycin demonstrated overall patient improvements.
The study is “making a plea that if your patient doesn’t turn around—not cured, just markedly improve by decreasing the number of stools by 75% or so roughly—in 3 days, then it is a reasonable thing to not add another drug, just take the oral vancomycin and go up,” study author Burke A. Cunha told MD Mag. “You go from 250 mg, if that’s what you’re using, to 500 mg and complete the 10-day course of therapy.”
Over a 24-month period, 160 eligible patients who tested positive for C. difficile were divided into 3 groups: conventional dosing group, high-dose escalation group, and primary high-dose treatment.
Sixty-five patients who were treated with 125 mg oral vancomycin were included in the first group. After an average of 14 days of therapy, they were clinically cured after an average of 5 days. Thirty-three patients who were originally treated with 250 mg vancomycin composed the second group. When investigators did not notice marked improvement after 72 hours with their initial therapy, they increased the oral vancomycin dose to 500 mg. Clinical resolution occurred at day 10, which was on average only 4 days after the escalation dose. There were 14 patients in the high-dose group treated with vancomycin 500 mg for the entire therapy course. Clinical resolution occurred after 5 days on average.
The team concluded that the study results have both stewardship implications and hospital epidemiology implications since physicians can reach the heart of the infectious problem sooner with dose escalation. After all, the hospital doesn’t want people with it at the hospital if they can help it, and they don’t want the infected patients at the hospital for longer than they need to be, Cunha said.
However, just as controversy over C difficile preventative measures exist, so do reactive treatments.
“The treatment of C difficile infection proves more complicated as not all individuals with primary C difficile infection achieve clinical cure and there is a high risk of recurrence,” study authors Michael Dieterle, an MD/PhD student, Krishna Rao, MD, and Vincent Young, MD, PhD, told MD Magazine® in a joint statement. “Current and emerging therapies both have shifted towards a common goal: treating C difficile infection by eliminating C difficile while retaining or reconstituting the native microbiota.”
While conventional management includes vancomycin for severe cases or fidaxomicin; sometimes, an addition of metronidazole is necessary as well. According to Dieterle, Rao, and Young, metronidazole can also be used to treat first-case recurrent infection. They suggested that improvements are needed for mild to moderate infections since18% to 27% of patients do not respond to treatment.
“Patients treated with fidaxomicin has been shown to have lower rates of recurrence after treatment compared to vancomycin, highlighting the potential effectiveness of narrow spectrum antibiotics for primary C difficile infection treatment and prevention of recurrence. However, the high cost of fidaxomicin makes it difficult to recommend for all patients,” the authors said.
As C difficile heads into 2019, physicians and investigators will likely continue to focus their attention on preventative medicine. However, treatment assessments will also likely continue, especially as investigators try to find a strategy that is both cost-effective and disease effective.
This article is part of MD Magazine's This Year In Medicine 2018 series. To read more from the series, check out the links below and follow us on Twitter at @MDMagazine.
Finding and Treating the Young Hepatitis C Patient
Influenza: Lessons from Last Season, Looking Ahead to the Next
Swiss Army Drug: Dupilumab Cuts into Asthma and Other Diseases
Advances in HIV Therapies and Comorbidity Research
Mind the Overlap: Reconsidering the Asthma-COPD Link