Emerging Tick-borne Infections in the Upper Midwest and Northeast United States Among Patients With Suspected Anaplasmosis.

Background: Emerging tick-transmitted illnesses are increasingly recognized in the United States (US). To identify multiple potential tick-borne pathogens in patients from the Upper Midwest and Northeast US with suspected anaplasmosis, we used state-of-the-art methods (polymerase chain reaction [PCR] and paired serology) to test samples from patients in whom anaplasmosis had been excluded. Methods: Five hundred sixty-eight patients without anaplasmosis had optimal samples available for confirmation of alternative tick-borne pathogens, including PCR and/or paired serology (acute-convalescent interval ≤42 days). Results: Among 266 paired serology evaluations, for which the median acute-convalescent sampling interval was 28 (interquartile range, 21-33) days, we identified 35 acute/recent infections (24 [9%] Borrelia burgdorferi; 6 [2%] Ehrlichia chaffeensis/Ehrlichia muris subsp eauclairensis [EC/EME]; 3 [1%] spotted fever group rickettsioses [SFGR], and 2 [<1%] Babesia microti) in 33 (12%) patients. Two had concurrent or closely sequential infections (1 B burgdorferi and EC/EME, and 1 B burgdorferi and SFGR). Using multiplex PCR and reverse-transcription PCR, we identified 7 acute infections (5/334 [1%] Borrelia miyamotoi and 2/334 [1%] B microti) in 5 (1%) patients, including 2 with B microti-B miyamotoi coinfection, but no Borrelia mayonii, SFGR, Candidatus Anaplasma capra, Heartland virus, or Powassan virus infections. Thus, among 568 patients with ruled-out anaplasmosis, 38 (6.7%) had ≥1 agent of tick-borne illness identified, with 33 patients (35 infections) diagnosed by paired serology and 5 additional patients (7 infections) by PCR. Conclusions: By identifying other tick-borne agents in patients in whom anaplasmosis had been excluded, we demonstrate that emerging tick-borne infections will be identified if specifically sought.

Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults.

BACKGROUND: Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. METHODS: We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir's safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. RESULTS: After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients' guts. CONCLUSIONS: Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir's safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. TRIAL REGISTRATION: NCT05416814; trial registered on June 13, 2022.

The human gut microbiome in critical illness: disruptions, consequences, and therapeutic frontiers.

With approximately 39 trillion cells and over 20 million genes, the human gut microbiome plays an integral role in both health and disease. Modern living has brought a widespread use of processed food and beverages, antimicrobial and immunomodulatory drugs, and invasive procedures, all of which profoundly disrupt the delicate homeostasis between the host and its microbiome. Of particular interest is the human gut microbiome, which is progressively being recognized as an important contributing factor in many aspects of critical illness, from predisposition to recovery. Herein, we describe the current understanding of the adverse impacts of standard intensive care interventions on the human gut microbiome and delve into how these microbial alterations can influence patient outcomes. Additionally, we explore the potential association between the gut microbiome and post-intensive care syndrome, shedding light on a previously underappreciated avenue that may enhance patient recuperation following critical illness. There is an impending need for future epidemiological studies to encompass detailed phenotypic analyses of gut microbiome perturbations. Interventions aimed at restoring the gut microbiome represent a promising therapeutic frontier in the quest to prevent and treat critical illnesses.

Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA).

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.

Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA).

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.

Human granulocytic anaplasmosis.

Human granulocytic anaplasmosis, a deer tick-transmitted rickettsial infection caused by Anaplasma phagocytophilum, is a common cause of undifferentiated fever in the northeast and upper Midwest United States. Patients are often initially diagnosed with a mild viral infection, and illness readily resolves in most cases. However, as many as 3% develop life-threatening complications and nearly 1% die from the infection. Although coinfections with Borrelia burgdorferi and Babesia microti occur, there is little evidence to suggest synergism of disease or a role for A phagocytophilum in chronic illness. No vaccine is available.

Recovery of the gut microbiome following fecal microbiota transplantation.

UNLABELLED: Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection. IMPORTANCE: Within the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for some patients with recurrent C. difficile infection, but its mechanism and long-term effects remain unknown. Our results provide insight into the structural and potential metabolic changes that occur following FMT, which may aid in the development of new treatment methods for C. difficile infection.

Staggered and tapered antibiotic withdrawal with administration of kefir for recurrent Clostridium difficile infection.

Daily administration of the probiotic kefir given in combination with a staggered and tapered antibiotic withdrawal regimen may resolve recurrent Clostridium difficile infection as effectively as fecal microbiota transplantation.

Fecal microbiota transplantation: a practical update for the infectious disease specialist.

Fecal microbiota transplantation (FMT) has been shown to be a superior therapeutic modality for the treatment of recurrent Clostridium difficile infection (RCDI). Recently the US Food and Drug Administration (FDA) determined that human stool should be classified as a biological agent and its use should be regulated to ensure patient safety. Consequently, the FDA determined that prescribers of FMT must possess an approved investigational new drug (IND) permit to administer FMT for the purpose of conducting research or treating any gastrointestinal condition other than RCDI. Although an IND is not required for use of FMT to treat RCDI, an IND is strongly encouraged and may ultimately be required. This article provides step-by-step guidance to infectious disease specialists on how to navigate the regulatory requirements and successfully obtain an IND before they can begin to use FMT as part of their clinical practice.

Treatment approaches including fecal microbiota transplantation for recurrent Clostridium difficile infection (RCDI) among infectious disease physicians.

BACKGROUND: Clostridium difficile infection (CDI) was the most common nosocomial infection in the U.S. in 2010. Most cases of CDI respond to a standard course of antibiotics, but recurrent C. difficile infections (RCDI) are increasingly common. Given the lack of randomized clinical trials, it is important to understand how infectious disease physicians are managing RCDI to inform future clinical research. METHODS: An electronic survey was conducted among members of the Emerging Infections Network (EIN) in October 2012. Respondents were asked to answer specific questions about their treatment approaches toward patients with CDI, including fecal microbiota transplantation (FMT). RESULTS: The overall response rate was 621/1212 (51%). The vast majority of respondents had cared for small to moderate numbers of patients with CDI over the prior 6 months, and reported recurrence rates were consistent with published data. Preferred treatment regimens for RCDI showed significant variance from recommendations published in national guidelines. Eighty percent (424/527) of the respondents would consider FMT for patients with RCDI, and of 149 who had FMT available at their institution, 107 (72%) had actually treated >1 patient with FMT in the preceding year. However, significant barriers to institutional adoption of FMT remain for many respondents, despite very good success rates with its use. CONCLUSIONS: Physicians who regularly care for patients with CDI use a variety of treatment approaches for treating severe or recurrent CDI cases. The results of our survey demonstrate that FMT is used by a growing number of infectious disease providers as an effective and safe treatment alternative for patients with multiple recurrences of C. difficile infection.

Fecal microbiome transplantation for recurrent Clostridium difficile infection: report on a case series.

BACKGROUND: Clostridium difficile infection (CDI) continues to increase in incidence and severity, and was the most common nosocomial infection in the USA in 2010. Most cases of CDI respond to a standard course of antibiotics, but recurrent C. difficile infection (RCDI) has become increasingly frequent, and alternative treatments are needed. We examined the efficacy of fecal microbiota transplantation (FMT) instilled into the upper gastrointestinal tract for RCDI. MATERIALS AND METHODS: The medical records for all patients treated with FMT during a 9-year period at a single institution in northern Minnesota were reviewed retrospectively. Eighty-nine FMT courses were provided by nasogastric tube to 87 patients, and demographic and clinical data were abstracted, including details of treatments prior to FMT, rate of FMT treatment success and clinical course during a 60-day post FMT follow up period. Fourteen FMT courses failed to meet criteria for inclusion. RESULTS: Each patient served as his or her own control, having failed standard treatment. After exclusions, the case series included 75 FMT courses administered to 74 patients. Fifty-nine FMT courses resulted in clinical resolution of diarrhea for a primary cure rate of 79%. Diarrhea relapsed following 16 FMT courses; in 9 of these cases diarrhea subsequently resolved after a single course of vancomycin. No adverse events were noted. CONCLUSIONS: Our findings parallel findings from other studies when FMT has been provided via the upper GI tract, and suggest that patients with recurrent CDI may resolve diarrhea by introducing stool from healthy donors into the upper GI tract via nasogastric tube.

Antiscience and ethical concerns associated with advocacy of Lyme disease.

Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven (sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health.

Treating Clostridium difficile infection with fecal microbiota transplantation.

Clostridium difficile infection is increasing in incidence, severity, and mortality. Treatment options are limited and appear to be losing efficacy. Recurrent disease is especially challenging; extended treatment with oral vancomycin is becoming increasingly common but is expensive. Fecal microbiota transplantation is safe, inexpensive, and effective; according to case and small series reports, about 90% of patients are cured. We discuss the rationale, methods, and use of fecal microbiota transplantation.

Scientific evidence and best patient care practices should guide the ethics of Lyme disease activism.

Johnson and Stricker published an opinion piece in the Journal of Medical Ethics presenting their perspective on the 2008 agreement between the Infectious Diseases Society of America (IDSA) and the Connecticut Attorney General with regard to the 2006 IDSA treatment guideline for Lyme disease. Their writings indicate that these authors hold unconventional views of a relatively common tick-transmitted bacterial infection caused by the spirochete Borrelia burgdorferi. Therefore, it should come as no surprise that their opinions would clash with the IDSA's evidence-based guidelines for the diagnosis and treatment of Lyme disease. Their allegations of conflict of interest against the IDSA resemble those made against the National Institutes of Health, the Food and Drug Administration and the Centers for Disease Control and Prevention in 2000, which were found to be baseless. It is the responsibility of all physicians and medical scientists to stand up to antiscientific, baseless and unethical attacks on those who support an evidence-based approach to caring for patients.

Fecal bacteriotherapy for recurrent Clostridium difficile infection.

Clostridium difficile infection (CDI) has emerged as a major complication associated with the use of systemic antimicrobial agents. Broad-spectrum antimicrobial agents disrupt the ecological bacterial balance in the colon and create an opportunity for C. difficile overgrowth with attendant production of toxins and clinical symptoms of colitis. Recommended therapies for CDI include oral administration of metronidazole or vancomycin for 10-14 days. However, 5% to 35% of patients experience infection relapse after completion of treatment. Recently, patients who failed to resolve their infection with conventional therapies and went on to develop chronic relapsing CDI were successfully treated with fecal bacteriotherapy. Stool obtained from a healthy individual was instilled from either end of the GI tract. Although the published experience with fecal bacteriotherapy is still limited, the published treatment results for 100 patients have demonstrated an average success-rate close to 90%. Fecal bacteriotherapy is a low tech procedure which is easy to perform, and breaks the cycles of repeated antibiotic use, which in turn reduces the risk of antibiotic associated resistance and adds potential cost savings when compared to repeated antibiotic administration and hospitalizations.