By Carol A. Kemper, MD, FACP
Dr. Kemper reports no financial relationships relevant to this field of study.
Probiotics and Lactobacillemia
SOURCE: Boumis E, Capone A, Galati V, et al. Probiotics and infective endocarditis in patients with hereditary hemorrhagic telangiectasia: A clinical case and review of the literature. BMC Infect Dis 2018;18:65.
Probiotics are consumed widely, including generalized use in many acute care medical facilities, as well as by health foodies worried about their fecal microbiota. And yet, whenever I speak with patients about their use, they seldom remember the name of the product, nor do they know the ingredients. Many are surprised to learn the contents often simply are no more than lactobacilli or various yeasts.
The risk of these kinds of products (other than to your pocketbook) generally is low, and such products seldom are pathogenic, mostly in those at risk, e.g., immunocompromised patients.
The authors of this study reported a case of an older patient with hereditary hemorrhagic telangiectasia (HHT) and a bioprosthetic aortic heart valve who presented with lactobacillemia. The patient had been diagnosed with HHT about seven years earlier, and experienced repeated episodes of epistaxis requiring laser coagulation and nasal packing. The patient had a history of recurrent Streptococcus mutans and S. aureus bacteremia, possibly related to these procedures and/or the packing, and had received multiple courses of antibiotics. As a result, the patient developed intermittent diarrhea and was self-medicating with up to seven different probiotic products, three of which contained Lactobacillus rhamnosus.
In 2017, the patient was hospitalized for fever of unknown origin, and multiple blood cultures grew L. rhamnosus. A transesophageal echocardiogram demonstrated a 1.1 cm vegetation on the aortic valve. The patient responded to a six-week course of amoxicillin-clavulanate and gentamicin.
A systematic review of the literature found only 10 cases of infective endocarditis associated with probiotic ingestion, six of whom had HHT. Most patients with lactobacillus bacteremia have had a recent dental extraction or disruption of intestinal mucosa that would increase the risk for gut translocation (e.g., colonoscopy). Surprisingly, immune compromise does not appear to be a significant predisposing factor for lactobacillus bacteremia. In a survey of 89 episodes of lactobacillus bacteremia, 47 (53%) of which were due to L. rhamnosus, more than two-thirds of patients (69%) were found to have gastrointestinal or hepatic neoplasm within 12 months.
Endocarditis from lactobacillus is rare. In one series of 73 cases of endocarditis from Lactobacillus species, 63% had predisposing valvular disease and 12% had a prior history of endocarditis. A dental procedure was identified as a likely risk factor in 47% of cases, but only three cases were linked to probiotic use.
It has been surmised that patients with HHT have disruption in nasal and gastrointestinal mucosa, predisposing them to bacteremia and endocarditis. As a result, patients with HHT undergoing nasal procedures involving disruption of mucosa and nasal packing should be considered candidates for pre-emptive antibiotics.
Probiotic strains of L. rhamnosus may appear identical to clinical strains, although they can be differentiated using pulsed-field gel electrophoresis (although this was not done for this case).
The Last Poliovirus Challenge
SOURCES: Collett MS, Hincks JR, Benschop K, et al. Antiviral activity of pocapavir in a randomized, blinded, placebo-controlled human oral poliovirus vaccine challenge model. J Infect Dis 2017;215:335; Sutter RW, Modlin JF, Zaffran M. Completing polio eradication: The case for antiviral drugs. J Infect Dis 2017;215:333; McNeil DG Jr. The war on polio, from the boots on the ground. The New York Times, Oct. 24, 2017: D4.
The Global Commission for the Certification of the Eradication of Poliomyelitis, which was launched in 1996-1997, is zeroing in on its final goals. At that time, poliovirus was still in circulation in many parts of the non-Western world, and thousands of children still were paralyzed every year. Since then, wild poliovirus type 2 has been officially eradicated from the world (although it still exists in the laboratory) and wild poliovirus type 3 has not been seen causing naturally occurring infection since 2012. At present, only pockets of circulating wild poliovirus type 3 continue to infect fewer than 100 children per year, mostly in remote, hard-to-reach areas of Afghanistan, Pakistan, and, to a lesser degree, Nigeria and neighboring countries.
Another goal of the global commission was the removal of Sabin type 2 strain from oral polio vaccine (OPV), which was accomplished in 2016, with the aim of diminishing the circulation of vaccine-derived virus. Immunocompromised individuals infected with OPV-derived strains of virus can excrete virus for years, and ultimately will remain the last “natural” reservoir of poliovirus — remaining a threat to those who are non-immune or unvaccinated.
This means that in addition to the final push to eradicate wildtype virus, there must be a renewed focus on the eradication of vaccine-strain virus still found circulating in some communities around the world. This can be done only by continued surveillance of sewage samples, identification of such individuals, and antiviral treatment aimed at eradicating their chronic infection. Currently, there is no effective treatment for immune deficiency-associated vaccine-derived infection.
In a randomized, placebo-controlled, blinded study, researchers examined the efficacy of a new enterovirus capsid inhibitor called pocapavir (V-073) (similar to another capsid inhibitor, pleconaril) in a group of adults aged 18 to 50 years, who received a single dose of monovalent OPV1. Participants previously had received four doses of childhood poliovirus vaccine, and had normal levels of total IgA immunoglobulin and evident PV-specific immunity. Study participants were randomized to active treatment or placebo in a 2:1 ratio. The treatment group was assigned one of four different dosing schemes of pocapavir: 1,600 mg daily for 14 days, started at either 24 hours or 72 hours post-mOPV1 challenge, with or without a fatty meal.
Participants entered the study facility in eight groups of 18 patients. They remained in isolation for 14 days, were assigned to one of three different bedrooms (six people per bedroom), and shared common dining, entertainment, and bathroom facilities. Cumulative and daily excretion of virus was measured in stool samples for 28 days. Neutralizing antibodies were measured at baseline and on the final study day.
Upon OPV oral challenge, 98% of individuals became infected and had virus-positive stools. Fecal virus was cleared within a median of 10 days in the treatment group vs. 13 days in the placebo group (P = 0.0019). Virus susceptibility was measured from the beginning to the end of study — and initially, 138 of 141 participants had pocapavir-sensitive virus. Three of the subjects were found to have pocapavir-resistant virus at baseline before the administration of study drug. Of those who initially excreted pocapavir-sensitive virus, 31%, including five patients in the placebo group, were resistant to pocapavir by the last positive stool.
Drug-resistant virus began to appear as early as day 2 to day 13, and the duration of excretion of drug-resistant virus ranged from 2 to 27 days (mean, 13 days). Drug levels measured for all 96 participants in the treatment group for each of the four different dosing regimens were well above the recognized in vitro antiviral inhibitory concentration for OPV1.
In the subgroup of 52 individuals treated with pocapavir with no evidence of resistant virus during the study course, virus was cleared more quickly from stools within a median of 5.5 days (range, 2-18 days).
These data indicate that transmission of OPV-derived virus and secondary infection within the facility were common. This is consistent with known data on the high frequency of secondary infection in the household setting — but serves as a stark reminder of just how infectious excretion of virus in stool may be — even in a controlled setting such as this.