Shira Doron

Probiotics: their role in the treatment and prevention of disease

A probiotic is a “live microbial food ingredients that, when ingested in sufficient quantities, exerts health benefits on the consumer”. Probiotics exert their benefits through several mechanisms; they prevent colonization, cellular adhesion and invasion by pathogenic organisms, they have direct antimicrobial activity and they modulate the host immune response. The strongest evidence for the clinical effectiveness of probiotics has been in their use for the prevention of symptoms of lactose intolerance, treatment of acute diarrhea, attenuation of antibiotic-associated gastrointestinal side effects and the prevention and treatment of allergy manifestations. More research needs to be carried out to clarify conflicting findings on the use of probiotics for prevention of travelers’ diarrhea, infections in children in daycare and dental caries, and elimination of nasal colonization with potentially pathogenic bacteria. Promising ongoing research is being conducted on the use of probiotics for the treatment of Clostridium difficile colitis, treatment of Helicobacter pylori infection, treatment of inflammatory bowel disease and prevention of relapse, treatment of irritable bowel syndrome, treatment of intestinal inflammation in cystic fibrosis patients, and prevention of necrotizing enterocolitis in premature infants. Finally, areas of future research include the use of probiotics for the treatment of rheumatoid arthritis, prevention of cancer and the treatment of graft-versus-host disease in bone marrow transplant recipients.

Viral prophylaxis in organ transplant patients.

Viral pathogens have emerged as the most important microbial agents having deleterious effects on solid organ transplant (SOT) recipients. Antiviral chemoprophylaxis involves the administration of medications to abort transmission of, avoid reactivation of, or prevent progression to disease from, active viral infection.Cytomegalovirus (CMV) is the major microbial pathogen having a negative effect on SOT recipients. CMV causes infectious disease syndromes, augments iatrogenic immunosuppression and is commonly associated with opportunistic superinfection. CMV has also been implicated in the pathogenesis of rejection. Chemoprophylactic regimens for CMV have included oral aciclovir (acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic strategies should be stratified, with the highest-risk patients receiving the most ‘potent’ prophylactic regimens.Herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir, valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive recipients.Primary varicella-zoster virus (VZV) after SOT is rare and most commonly seen in the paediatric transplant population because of VZV epidemiology. Zoster occurs in 5–15% of patients, usually after the sixth post-transplant month. Prophylactic regimens for zoster are neither practical nor cost effective after SOT because of the late onset of disease and low proportion of affected individuals. All SOT recipients should receive VZV immune globulin after contact with either varicella or zoster.Epstein-Barr virus has its most significant effect in SOT as the precipitating factor in the development of post-transplant lymphoproliferative disorders. Antiviral agents that could be effective are the same as those used for CMV, but indications for and effectiveness of prophylaxis are poorly established.Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important pathogens in the SOT population as indications for transplantation. So-called ‘prophylaxis’ for recurrent HBV and HCV after liver transplantation is controversial, suppressive rather than preventive, and potentially lifelong.Influenza infection after SOT is acquired by person-to-person contact. During epidemic periods of influenza, transplant populations experience a relatively high frequency of infection, and influenza may affect immunosuppressed SOT recipients more adversely than immunocompetent individuals. Antiviral medications for prevention of influenza are administered as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in circumstances such as influenza epidemics and nosocomial outbreaks, and after exposure to a symptomatic individual during ‘flu season’.

Probiotics for prevention of antibiotic-associated diarrhea.

Antibiotic-associated diarrhea (AAD) occurs in approximately 25% of patients receiving antibiotics. Hospitalized patients with AAD are at increased risk for nosocomial infections and have a higher mortality. Probiotics are living microorganisms used to restore gut health by changing the intestinal microbiota. Several have been studied for the prevention of AAD. Five meta-analyses of trials of probiotics for the prevention of AAD have been performed. The results showed an overall reduction in the risk of AAD when probiotics were coadministered with antibiotics. McFarland conducted the largest meta-analysis to date analyzing 25 randomized controlled trials of probiotics for the prevention of AAD including 2810 subjects. More than half of the trials demonstrated efficacy of the probiotic. In particular, Lactobacillus GG, Saccharomyces boulardii, and the probiotic mixtures were effective. The Cochrane Database of Systematic Reviews published a review of the literature on the use of probiotics for the prevention of pediatric AAD, including 10 randomized trials testing 1986 children. The per protocol pooled analysis, but not the intent-to-treat analysis, showed that probiotics are effective for preventing AAD with the number needed to treat to prevent 1 case of diarrhea being 10. Lactobacillus GG, Bacillus coagulans, and S. boulardii appeared to be most effective. Probiotics are generally safe, however, they should be used with caution in patients who have compromise of either the immune system or the integrity of the intestinal mucosa, and in the presence of a central venous catheter.

Histopathologically Proven Poliomyelitis with Quadriplegia and Loss of Brainstem Function Due to West Nile Virus Infection

Recent electrophysiological and histopathological reports point to motor neurons in the anterior horn of the spinal cord and the brainstem as targets of severe West Nile virus (WNV) infection. We report histopathological confirmation of this poliomyelitis-like syndrome in a patient with WNV infection in Massachusetts.

SYMPOSIUM ON ANTIMICROBIAL THERAPYAntimicrobial Stewardship

Antimicrobial resistance is increasing; however, antimicrobial drug development is slowing. Now more than ever before, antimicrobial stewardship is of the utmost importance as a way to optimize the use of antimicrobials to prevent the development of resistance and improve patient outcomes. This review describes the why, what, who, how, when, and where of antimicrobial stewardship. Techniques of stewardship are summarized, and a plan for implementation of a stewardship program is outlined.

Hypogammaglobulinemia in liver transplant recipients: incidence, timing, risk factors, and outcomes.

Background. Recent studies suggest a substantial incidence of posttransplant hypogammaglobulinemia and an association with infection. Methods. We conducted a retrospective analysis of immunoglobulin (Ig) G levels from blood prospectively collected during a randomized double-blind placebo-controlled trial of cytomegalovirus (CMV) immune globulin that included 146 patients who underwent liver transplantation between December 1987 and June 1990. Serum samples collected at baseline and approximately weeks 4, 8, 12, 16, 24, and 32 posttransplant were analyzed. Hypogammaglobulinemia was defined as having at least one IgG level below 560 mg/dl. A variety of variables were analyzed as potential risk factors and outcomes of hypogammaglobulinemia. Results. A total of 613 samples from 112 patients were analyzed. Twenty-nine (26%) patients had posttransplant hypogammaglobulinemia. Fourteen (12.5%) had hypogammaglobulinemia at the time of their baseline measurement. There was a strong association between hypogammaglobulinemia and both one-year (P=0.0490) and five-year mortality (P=0.0187), even when adjusted for variables known to be associated with mortality (HR for one-year mortality 3.08, confidence interval 1.20, 7.91). Risk factors for hypogammaglobulinemia included only non A/non B hepatitis and “other diagnosis” (a category made up of rare causes of liver disease). None of the infectious outcomes examined, including CMV infection, CMV disease, bacteremia or invasive fungal disease, or rejection were significantly associated with hypogammaglobulinemia. Conclusions. In orthotopic liver transplant recipients we found a 26% incidence of posttransplant hypogammaglobulinemia. Approximately half of these patients were hypogammaglobulinemic at baseline. A strong association between hypogammaglobulinemia and mortality was seen. Prospective studies are needed to further elucidate the risk factors and outcomes of posttransplant hypogammaglobulinemia.

The Impact of Gown-Use Requirement on Hand Hygiene Compliance

BACKGROUND Hand hygiene compliance remains low, despite its effectiveness in preventing infections. Gowns are routinely used to reduce dissemination of organisms within hospitals. Use of gowns is time consuming and costly, and their effectiveness, compared with that of hand hygiene alone, is debated. Among the arguments supporting a gown-use requirement is the potential to boost awareness of infection control, leading to improved hand hygiene compliance. METHODS Hand hygiene compliance was recorded in a 14-month crossover trial comparing compliance at 2 intensive care units during periods with and without a gown-use requirement. RESULTS During 170 h of observation, 1619 hand hygiene opportunities were recorded. Compliance was 10% before care was given and 36% after care was given. Compliance with glove and gown use was 62% and 63%, respectively. After-care hand hygiene compliance for nurses, physicians, and therapists was 40%, 38%, and 22%, respectively. Compliance after patient contact, body fluid contact, and other in-room activity was 42%, 48%, and 22%, respectively. For periods with and without a gown-use requirement, overall after-care compliance (37% vs. 34%) and rates by personnel and activity type were similar. In the subgroup of patients on contact precautions, hand hygiene compliance during the period with a gown-use requirement versus the period without a gown-use requirement was 11% versus 10% (P=.85) before care was given and 45% versus 39% (P=.09) after care was given. In this subgroup, after adjustment for type of in-room activity, medical personnel, intensive care unit, and observer, the predicted after-care hand hygiene compliance during periods with and without a gown-use requirement was 48% versus 41% (P=.02). CONCLUSIONS The hypothesis that a gown-use requirement might improve hand hygiene compliance in the intensive care unit could not be confirmed. In the subgroup of patients on contact precautions, improvement in hand hygiene compliance associated with the gown-use requirement was small and did not affect precare rates.

A Nationwide Survey of Antimicrobial Stewardship Practices

OBJECTIVE The goal of this study was to characterize hospital antimicrobial stewardship practices nationwide and to identify factors associated with the presence of these programs. METHODS The first web-based survey was sent in 2009 to members of the Yankee Alliance and the Premier Healthcare Alliance, nationwide organizations of health-care providers. The second survey, a slightly modified version of the first, was sent in 2010 to a commercially purchased list of hospital pharmacy director e-mail addresses. RESULTS A total of 406 responses were received from ~5890 providers targeted, for an overall response rate of ~7%. More than one half (206 of 406) of the respondents reported having what they considered to be a formal antimicrobial stewardship program (ASP). Among all respondents regardless of presence or absence of an ASP, 96.4% (351 of 364) were using some form of antimicrobial stewardship technique. Of those respondents working in hospitals without an ASP, 63.3% (114 of 180) had considered implementing one. After controlling for all significant variables, those that remained which were significantly associated with having an ASP were survey (Premier vs commercial), having an infectious disease consultation service, and having an infectious disease pharmacist. CONCLUSIONS In this survey of 406 respondents from across the country, we found that just more than one half of hospitals had what they considered to be formal ASPs; however, the vast majority were using stewardship techniques to optimize the use of antibiotics. Common barriers to implementation of ASPs included staffing constraints and insufficient funding.

Impact of an Institution-Specific Hospital-Acquired Pneumonia Protocol on the Appropriateness of Antibiotic Therapy and Patient Outcomes

Study Objective. To evaluate the impact of a hospital‐acquired pneumonia (HAP) protocol on appropriateness of empiric antibiotic therapy, antibiotic deescalation, antibiotic duration, patient mortality, and length of stay.

A Multifaceted Approach to Education, Observation, and Feedback in a Successful Hand Hygiene Campaign

BACKGROUND Prevention of health care-associated infections starts with scrupulous hand hygiene (HH). Improving HH compliance is a major target for the World Health Organization Patient Safety Challenge and is one of The Joint Commissions National Patient Safety Goals. Yet, adherence to HH protocols is generally poor for health care professionals, despite interventions designed to improve compliance. At Tufts Medical Center (Boston), HH compliance rates were consistently low despite the presence of a traditional HH campaign that used communication and education. METHODS A comprehensive program incorporated strong commitment by hospital leadership-who were actively involved in responsibilities previously only performed by infection preventionists and quality and patient safety staff-dedication of financial resources, including securing a grant; collaborating with a private advertising firm in a marketing campaign; and employing a multifaceted approach to education, observation, and feedback. RESULTS This campaign resulted in a rapid and sustained improvement in HH compliance: Compared with the mean HH compliance rate for the six months before the campaign (72%), postcampaign HH compliance (mean = 94%) was significantly greater (p < .0001). Factors contributing to the success of the campaign included the development of the marketing campaign to fit this academic medical centers particular culture, strong support from the medical center leadership, a multifaceted educational approach, and monthly feedback on HH compliance. CONCLUSIONS A comprehensive campaign resulted in rapid and sustained improvement in HH compliance at an academic medical center after traditional communication and education strategies failed to improve HH performance.