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Biomedical subjects

L V McFarland

Publications and source records attributed to L V McFarland.

At least 19 recordsLinked to original sources
PubMed2001

Biotherapeutic agents in the treatment of infectious diarrhea.

Biotherapeutic agents offer unique advantages over traditional treatments for infectious diarrhea, and several have been shown to be effective (Table 4). These therapeutic microbial agents are most effective in types of infectious diseases that are associated with a disruption of the normal intestinal microecology (e.g., AAD, C. difficile disease). The impact of biotherapeutic agents on rotaviral diarrhea is of special clinical importance because this is the most common cause of pediatric diarrhea, and there is no defined treatment. Strong efforts need to be made to limit antibiotic exposure in children. Biotherapeutic agents offer a safe and effective nonantibiotic method of treating this important pathogen, especially after the withdrawal of a rotaviral vaccine from the market by the FDA. However, for many biotherapeutic agents, well-done, placebo-controlled trials still are lacking, and not all types of infectious diarrhea respond to these agents. Continued research in this innovative therapeutic area is warranted.

Adult↗
PubMed2000

The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii.

Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD. In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; P=.05). No serious adverse reactions were observed in these patients. Comparison of data from this trial with data from previous studies indicates that recurrent CDD may respond to a short course of high-dose vancomycin or to longer courses of low-dose vancomycin when either is combined with S. boulardii.

Aged↗
PubMed2000

Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting.

OBJECTIVE: The goal of this study was to determine the prevalence of Clostridium difficile diarrhea (CDD) and the risk for CDD associated with different oral antibiotics commonly used in the ambulatory care setting. METHODS: The prevalence of CDD was determined for enrollees in 4 UnitedHealth Group-affiliated health plans between January 1, 1992, and December 31, 1994. Cases were identified based on the presence of an inpatient or outpatient claim with a primary diagnosis of diarrhea, a pharmacy claim for a prescription drug used to treat CDD, or a physician or facility claim for the C. difficile toxin test, and were confirmed using full-text medical records. Within a retrospective cohort design, periods of risk for CDD were defined on the basis of duration of antibiotic therapy. To control for potential selection bias created by heterogeneous rates of C. difficile testing and to limit confounding due to multiple antibiotic exposures, we used a nested case-control design, restricting eligibility to subjects who underwent screening for C. difficile and who had been exposed to only 1 antibiotic risk period with a single antibiotic. RESULTS: The global prevalence of CDD in 358,389 ambulatory care enrollees was 12 per 100,000 person-years. In the nested case-control study, after controlling for other risk factors, 2 antibiotics demonstrated an increased association with CDD: cephalexin (odds ratio [OR] = 7.5, 95% CI = 1.8 to 34.7) and cefixime (OR = 6.4, 95% CI = 1.2 to 39.0). CONCLUSIONS: Although CDD is thought to occur primarily in hospitalized patients, it was found to be present in an ambulatory care population, but at a low frequency. In this population, it appeared to be associated with 2 cephalosporins but not with other types of antibiotics usually linked with nosocomial CDD. Because the frequency of C. difficile testing was shown to be more common with high-risk antibiotics, CDD may be underdiagnosed in the ambulatory care setting.

Adolescent↗
PubMed2000

Beneficial microbes: health or hazard?

Normal microbial flora support the health of the host by diverse mechanisms. When antibiotics, stress, disease or medications disrupt normal microflora, the ability to ward off infection by pathogens is compromised. The use of beneficial microbes (also known as biotherapeutic agents, probiotics, synbiotics) has been shown to be an effective therapeutic agent for some diseases. Various types of diarrhoea (antibiotic-associated diarrhoea, Clostridium difficile disease, traveller's diarrhoea) are most responsive to these beneficial microbes. Serious risks associated with these microbes are largely theoretical at this point, but the risks need to be studied as the use of these beneficial microbes increases in popularity. Beneficial microbes are living organisms used as therapeutic agents to restore the health of the host in times when normal microflora have been disturbed. The efficacy to prevent or treat diarrhoea has been documented in multiple large, placebo-controlled, blinded clinical trials with only a few of these beneficial microbes. Risks of these beneficial microbes are limited, but potential risks have not been extensively studied in large numbers of patients.

Diarrhea↗
PubMed1999

Microecologic approaches for traveler's diarrhea, antibiotic-associated diarrhea, and acute pediatric diarrhea.

Bacterial and viral diarrhea remain important causes of morbidity and mortality throughout the world. Current concerns with medical costs, increasing frequency of antibiotic resistance, and overuse of antibiotics in general have redirected therapeutic approaches for diarrhea from traditional drugs to the use of living therapeutic organisms. Awareness of the important role of normal flora in the microecology of the intestines in fighting infection, along with the recent availability of well-controlled clinical trials for these agents, has brought microecologic therapies to the forefront of clinical practice.

Acute Disease↗
PubMed1999

Behaviour of Saccharomyces boulardii in recurrent Clostridium difficile disease patients.

BACKGROUND: Despite recent interest in therapeutic microorganisms taken orally, little is known about the pharmacodynamics of these agents in a target population of patients with disease. The present study reports the stool concentrations of Saccharomyces boulardii in a patient population with Clostridium difficile disease (CDD) and correlates stool concentrations with efficacy. METHODS: Patients with recurrent CDD all received a 10-day standard antibiotic regimen together with 28 days of S. boulardii or placebo. Stool samples were collected from patients at various time points and assayed for S. boulardii. RESULTS: The mean concentration of S. boulardii of patients who recurred was 2.5 x 104 CFU/g compared to 1 x 106 CFU/g in patients that did not recur (P=0.02). Patients with low yeast concentrations in their stools (<104/g) recurred more often (14/15, 93%) compared with patients with higher levels (19/35, 54%, P=0.007). Clearance of S. boulardii was rapid; only 4% had positive stools 3 days after stopping dosing. CONCLUSIONS: After chronic dosing of S. boulardii, patients with low stool concentrations had a higher likelihood of recurrence of CDD. Stool concentrations were also lower during periods of diarrhoea. These results show the importance of characterizing the dynamics of a therapeutic microorganism in patients with disease, as kinetic studies in healthy volunteers may not give a true reflection of the disturbed microecology in the disease state.

Anti-Bacterial Agents↗
PubMed1999

Recurrent Clostridium difficile disease: epidemiology and clinical characteristics.

OBJECTIVE: To describe the epidemiology, diagnosis, risk factors, patient impact, and treatment strategies for recurrent Clostridium difficile-associated disease (CDAD). DESIGN: Data were collected as part of a blinded, placebo-controlled clinical trial testing a new combination treatment for recurrent CDAD. Retrospective data regarding prior CDAD episodes were collected from interviews and medical-chart review. Prospective data on the current CDAD episode, risk factors, and recurrence rates were collected during a 2-month follow-up. SETTINGS: National referral study. PARTICIPANTS: Patients with recurrent CDAD. INTERVENTIONS: Treatment with a 10-day course of low-dose (500 mg/d) or high-dose (2 g/d) vancomycin or metronidazole (1 g/d). RESULTS: Recurrent CDAD was found to have a lengthy course involving multiple episodes of diarrhea, abdominal cramping, nausea, and fever. CDAD may recur over several years despite frequent treatment with antibiotics. Recurrence rates were similar regardless of the choice or dose of antibiotic. Recurrent CDAD is not a trivial disease: patients may have multiple episodes (as many as 14), may require hospitalization, and the mean lifetime cost of direct medical care was $10,970 per patient. Fortunately, the disease does not become progressively more severe as the number of episodes increase. Two risk factors predictive for recurrent CDAD were found: increasing age and a decreased quality-of-life score at enrollment. CONCLUSIONS: Recurrent CDAD is a persistent disease that may result in prolonged hospital stays, additional medical costs, and rare serious complications.

Adolescent↗
PubMed1998

[Risk factor for antibiotic-associated diarrhea. A review of the literature].

Antibiotic associated diarrhea (AAD) is a common adverse reaction to most types of antibiotics with frequencies ranging from 5-39%, depending upon the specific type of antibiotic and the presence of other risk factors. The pathogenesis of antibiotic associated diarrhea is mediated through the disruption of the normal flora and overgrowth of pathogens or through metabolic imbalances. Beside risk factors associated with the type and duration of antibiotic therapy, host factors include the extremes of age (< 6 years or > 65 years), severe underlying disease, presence of other chronic intestinal conditions, immunosuppression, prior history of AAD and exposures during recent hospitalizations (surgery, nasogastric tube feeding). Factors which have not been significantly associated with antibiotic associated diarrhea include gender, dose or route of the inciting antibiotic and inflammatory bowel disease. The clinical impact of AAD is reflected by potential severity of the illness (PMC), possible consequences of the disruption in the treatment of the primary infection, higher medical costs, increased hospital stays and increased rates of morbidity and mortality. The key to decreasing these consequences is prompt diagnosis followed by effective treatment and institution of control measures and preventive treatments in patients at risk.

Adolescent↗
PubMed1997

Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial.

Recurrent Clostridium difficile diarrhea (RCDD) occurs in 20% of patients after they have received standard antibiotic treatment with vancomycin or metronidazole, but the reasons for the recurrences are largely unknown. Patients receiving vancomycin or metronidazole for active C. difficile diarrhea (CDD) were referred to our study centers for treatment and a 2-month follow-up as part of a randomized placebo-controlled trial. Sixty patients had RCDD (median number of episodes, 3.0; range, 2-9 episodes) and 64 were having their first episode of CDD. Patients with RCDD had more-severe abdominal pain and were more likely to have fever but initially responded well to antibiotic therapy. Data on sequential episodes showed no progression in disease severity. Five factors were associated with a higher risk of RCDD: the number of previous CDD episodes, onset of the initial disease in the spring, exposure to additional antibiotics for treatment of other infections, infection with immunoblot type 1 or 2 strains of C. difficile, and female gender. These factors may help to identify patients who are more likely to develop RCDD and require careful medical supervision.

Adult↗
PubMed1996

Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections.

OBJECTIVE: To evaluate the potential of biotherapeutic agents (microorganisms with therapeutic properties) for the prevention and/or treatment of selected intestinal and vaginal infections. DATA SOURCES: The MEDLINE database was searched for all relevant articles published between 1966 and September 1995. Search terms used were biotherapeutic agent, probiotic, Lactobacillus, Saccharomyces, Bifidobacterium, Candida, gastrointestinal- system, vaginitis, vaginosis-bacterial, and related terms. The bibliographies of obtained articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled human studies on biotherapeutic agents were reviewed. English-language open trials, case series and reports, and animal studies were reviewed only if they were especially relevant to providing information on the potential efficacy, adverse effects, or mechanisms of action of these agents. DATA SYNTHESIS: Placebo-controlled studies have shown that biotherapeutic agents have been used successfully to prevent antibiotic-associated diarrhea (Lactobacillus caseiGG, bifidobacterium longum, B longum with L acidophilus, and Saccharomyces boulardii), to prevent acute infantile diarrhea (Bifidobacterium bifidum with Streptococcus thermophilus), to treat recurrent Clostridium difficile disease (S boulardii), and to treat various other diarrheal illnesses (Enterococcus faecium SF68, L caseiGG, and S boulardii). There is also evidence for Lactobacillus acidophilus in the prevention of candidal vaginitis. Few adverse effects have been reported. However, many of the studies tested only small numbers of patients or volunteers. CONCLUSIONS: There is now evidence that administration of selected microorganisms is beneficial in the prevention and treatment of certain intestinal and, possibly, treatment of vaginal infections. In an effort to decrease the reliance on antimicrobials, the time has come to carefully explore the therapeutic applications of biotherapeutic agents.

Adult↗
PubMed1995

Epidemiology of infectious and iatrogenic nosocomial diarrhea in a cohort of general medicine patients.

BACKGROUND: Nosocomial diarrhea is a common problem in hospitals, but the epidemiology, causes, and consequences of infectious and iatrogenic nosocomial diarrhea are rarely documented in follow-up or surveillance studies of nosocomial infections. The objective of this study was to describe the epidemiology of nosocomial diarrhea in a cohort study of hospitalized patients. METHODS: The setting was a general medicine ward with a total of 30 beds in private or semiprivate rooms in a county hospital. A prospective cohort study of all consenting patients in the study ward was performed during an 11-month period. Patients were interviewed and cultures were obtained to check for stool pathogens within 48 hours of admission, and patients were followed up during their stay in the study ward. Data from medical notes, laboratory tests, antibiotic logs, and patient interviews were collected daily. RESULTS: Among the 382 eligible patients, nosocomial diarrhea developed in 126 (32.9%): 37 cases were of infectious origin, 57 were iatrogenic, and 32 were of unknown origin. The most common causes of nosocomial diarrhea were Clostridium difficile and antibiotic therapy. Multivariate analysis revealed four risk factors for infectious nosocomial diarrhea: age, length of stay, number of antibiotics, and nasogastric tube feedings. Multivariate analysis also revealed four risk factors for iatrogenic nosocomial diarrhea: number of antibiotics, current gastrointestinal conditions, current renal conditions, and recent surgery. Comorbidity associated with nosocomial diarrhea included increased risk of acquiring another type of nosocomial infection, increased risk of death, and increased length of stay. CONCLUSIONS: Nosocomial diarrhea was found to be common and associated with an additional burden of comorbidity. Analyses indicated different risk factors, depending on the etiology of nosocomial diarrhea (infectious or iatrogenic). Further studies are recommended to document the epidemiology and cost analysis of nosocomial diarrhea in other hospital populations.

Adult↗