Johan S. Bakken

The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America

Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed.

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.

Recovery of the Gut Microbiome following Fecal Microbiota Transplantation

ABSTRACT 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. 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.

Clinical diagnosis and treatment of human granulocytotropic anaplasmosis.

Abstract:  Tick‐borne rickettsiae in the genera Ehrlichia and Anaplasma are intracellular bacteria that infect wild and domestic mammals and, more recently, man. The increased desire of humans for recreational activities outdoors has increased the exposure to potential human pathogens that previously cycled almost exclusively within natural, nonhuman enzootic hosts. Anaplasma phagocytophilum causes an acute, nonspecific febrile illness of humans previously known as human granulocytotropic ehrlichiosis (HGE) and now called human granulocytotropic anaplasmosis (HGA). The first patient to have recognized HGA was hospitalized at St Marys Hospital in Duluth, Minnesota, USA in 1990. However, the clinical and laboratory presentation of this infection remained undefined until 1994, when Bakken and collaborators published their experience with 12 patients who had HGA. By the end of December 2004, at least 2,871 cases of HGA had been reported from 13 U.S. states to the Centers for Disease Control and Prevention (CDC). A limited number of laboratory‐confirmed cases have been reported from countries in Europe, including Austria, Italy, Latvia, the Netherlands, Norway, Poland, Slovenia, Spain, and Sweden. Ixodes persulcatus‐complex ticks are the arthropod hosts for Borrelia burgdorferi, the agent of Lyme borreliosis, and are also the arthropod hosts for A. phagocytophilum. Most cases of HGA have been contracted in geographic regions that are endemic for Lyme borreliosis. Male patients outnumber female patients by a factor of 3 to 1 and as many as 75% of patients with HGA have had a tick bite prior to their illness. Seroepidemiologic studies have demonstrated that HGA for the most part is a mild or even asymptomatic illness. However, older individuals and patients who are immunocompromised by natural disease processes or medications may develop an acute, influenza‐like illness characterized by high fever, rigors, generalized myalgias, and severe headache. Local skin reactions at the site of the tick bite have not been described, and nonspecific skin rashes have been reported only occasionally. Anaplasmosis is associated with variable but suggestive changes in routine laboratory test parameters. Most patients develop transient reductions in total leukocyte and platelet concentrations. Relative granulocytosis accompanied by a left shift and lymphopenia during the first week of illness has been reported frequently. Serum hepatic transaminase concentrations usually increase two‐ to fourfold, and inflammatory markers, such as C‐reactive protein and the erythrocyte sedimentation rate, rise during the acute phase. Abnormal laboratory findings may return toward normal range for patients who have been ill for more than 7 days, which may obfuscate the clinical decision making. Characteristic clusters of bacteria (morulae) are observed in the cytoplasm of peripheral blood granulocytes in 20% to 80% of infected patients during the acute phase of illness. The clinical diagnosis may be confirmed retrospectively by specific laboratory tests, which include positive polymerase chain reaction (PCR), identification of A. phagocytophilum in culture of acute‐phase blood, or the detection of specific antibodies to A. phagocytophilum in convalescent serum. Virtually all patients have developed serum antibodies to A. phagocytophilum after completion of antibiotic therapy, and demonstration of seroconversion by indirect immunofluorescent antibody testing of acute‐phase and convalescent‐phase serum samples is currently the most sensitive and specific tool for laboratory confirmation of HGA. Treatment with doxycycline usually results in rapid improvement and cure. Most patients with HGA have made an uneventful recovery even without specific antibiotic therapy. However, delayed diagnosis in older and immunocompromised patients may place those individuals at risk for an adverse outcome, including death. Thus, prompt institution of antibiotic therapy is advocated for any patient who is suspected to have HGA and for all patients who have confirmed HGA.

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.

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.

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.

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.

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 IDSAs 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.

Feces transplantation for recurrent Clostridium difficile infection: US experience and recommendations

No abstract available. (Published: 29 May 2015) Citation: Microbial Ecology in Health & Disease 2015, 26: 27657 - http://dx.doi.org/10.3402/mehd.v26.27657