Papers by Barbara Laughon
The Journal of Infectious Diseases, Aug 1, 1991
Page 1. 244 From the National Institutes of Health Summary of the Workshop on Future Directions i... more Page 1. 244 From the National Institutes of Health Summary of the Workshop on Future Directions in Discovery and Development of Therapeutic Agents for Opportunistic Infections Associated with AIDS Barbara E. Laughon, HS ...
Antimicrobial Agents and Chemotherapy, Oct 1, 1987
The purpose of this study was to compare the antimicrobic efficacies of four formulations of chlo... more The purpose of this study was to compare the antimicrobic efficacies of four formulations of chlorhexidine gluconate (CHG) for handwashing under frequent-use conditions. Fifty volunteers were assigned by block randomization to one of five products: one of two liquid detergents containing 4% CHG, a liquid detergent containing 2% CHG, a foam containing 4% CHG, and a nonantiseptic soap (control). Subjects washed their hands by a standardized technique 15 times per day for 5 days. After days 1 and 5 of handwashing, there was a significant reduction in log CFU for subjects using all four CHG-containing products compared with subjects using control soap and for subjects within each group after days 1 and 5 compared with the base-line CFU counts (all P < 0.05). There were no significant differences between the four CHG products at any testing time. We conclude that all four formulations are satisfactory for clinical use.
PubMed, 1986
Aerobic gram negative bacterial infections occur commonly in patients with acute leukemia undergo... more Aerobic gram negative bacterial infections occur commonly in patients with acute leukemia undergoing intensive chemotherapy-induced bone marrow aplasia, and often arise from the gastrointestinal (GI) tract. The value of oral prophylactic norfloxacin (400 mg every 12 hours) in preventing bacterial infections was determined for 68 adults with acute leukemia by a prospective, randomized, double-blind, placebo-controlled trial. The efficacy of norfloxacin administered prophylactically throughout the course of intensive therapy and deep (less than 100 mm/3), prolonged (median 32 day) granulocytopenia against infections arising from the GI tract was demonstrated by its impact on the clinical manifestations of infection, microbiologically documented gram negative bacterial infections, overall antibiotic management, and GI colonization. Although there was no difference with respect to survival, norfloxacin decreased overall morbidity associated with gram-negative infections, was well tolerated, did not impinge on systemic antibacterial or antitumor therapy, and did not predispose to the development of bacteria resistant either to itself or to multiple other antibiotics. The advantages of norfloxacin relative to other oral agents used for GI prophylaxis and the potential beneficial effects of norfloxacin or overall medical cost are discussed. Oral norfloxacin achieves the goals of GI prophylaxis by effectively suppressing early infection arising from the GI tract and inhibiting GI colonization by multiply resistant pathogens that could give rise to late-onset infections during profound chemotherapy-induced bone marrow aplasia.
PubMed, Feb 1, 1986
Anaerobic bacteria from the oral flora are important causes of aspiration pneumonia and lung absc... more Anaerobic bacteria from the oral flora are important causes of aspiration pneumonia and lung abscess. However, the pulmonary antibacterial response to these organisms has not been well described. To define this, mice were intratracheally inoculated with 10(9) Bacteroides gingivalis, a member of the B. melaninogenicus group, and a common clinical isolate from periodontal disease and anaerobic pulmonary infections. Studies after intratracheal challenge included bacteriologic and histopathologic examination, pulmonary cellular response, lactic dehydrogenase (LDH) and albumin levels in lung lavage fluid, and wet lung weight. Overall mortality was 25%. In the surviving animals, pulmonary lavage showed a marked recruitment of polymorphonuclear leukocytes that was associated with significant bacterial killing by 48 h. Histopathologic examination showed an acute, severe necrotizing bronchopneumonia. Pulmonary abscess formation occurred in 37% of animals. Severe parenchymal damage was further documented by a marked increase in LDH levels in lavage fluids. Mean LDH levels in lavage fluid increased to 850 +/- 25 units/first lavage at 24 h postchallenge compared with control values of 65 +/- 10 units/first lavage. Lung lavage also demonstrated an extensive influx of serum albumin consistent with injury to the alveolar capillary membrane. Albumin levels in lung lavage were highest at 24 h after intratracheal challenge (3.25 +/- 0.3 mg/first lavage), whereas lavage fluid from control mice had nondetectable albumin levels. Wet lung weights maximally increased from 0.12 +/- 0.01 g in control mice to 0.28 +/- 0.03 g 24 h after bacterial-challenge. These data demonstrate tht B. gingivalis causes marked inflammation in the lung that progresses to severe bronchopneumonia and lung abscess.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Clinical Microbiology, Aug 1, 1983
An enzyme immunoassay (enzyme-linked immunosorbent assay [ELISA]) to detect hamster antibody to t... more An enzyme immunoassay (enzyme-linked immunosorbent assay [ELISA]) to detect hamster antibody to toxins A and B of Clostridium difficile was developed in which toxin preparations are used to coat the solid phase. The specificity of the assay was supported by blocking tests with the toxin preparations and proteins from a nontoxigenic strain. Sera from immunized and control hamsters were tested by this technique, and results were compared with those from a cytotoxicity neutralization assay. Antibody to toxins A and B assayed by ELISA showed a close quantitative correlation with antibody titers obtained by cytotoxicity neutralization. The ELISA assays described appear to provide a sensitive, specific, and practical method to define the prevalence of antibody to C. difficile toxins. These assays could be readily applied to human sera to examine and study the immune response of patients with C. difficile-induced disease. Clostridium difficile has been implicated as
Current Opinion in Pulmonary Medicine, May 1, 2019
Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial... more Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: "This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition". Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. Rapid communication: key changes to treatment of multidrug-and rifampicin-resistant tuberculosis (MDR/RR-TB). Licence: CC BY-NC-SA 3.0 IGO.
Journal of Clinical Microbiology, Feb 1, 1985
Gastroenterology, Oct 1, 1989
Annals of Internal Medicine, Jun 1, 1994
Journal of the American Geriatrics Society, Apr 1, 1990
Clostridium difficile causes pseudomembranous colitis and is responsible for 20% to 25% of cases ... more Clostridium difficile causes pseudomembranous colitis and is responsible for 20% to 25% of cases of postantibiotic diarrhea. In an earlier study, nursing‐home patients with C. difficile infection were noted to have a high mortality rate. Because most of these infected patients had been treated with antibiotics, it was not clear whether this high mortality rate was associated with C. difficile infection or simply with antibiotic treatment. A prospective study was carried out to determine the rate of postantibiotic C. difficile colonization and risk factors for infection in patients in a 233‐bed long‐term care facility, as well as to determine whether C. difficile infection is associated with increased mortality. During a six‐month period 150 courses of antibiotics were prescribed for 108 patients. Stool specimens were collected from 36 (33%) patients following the first course of antibiotic treatment, and 12 (33%) were infected with C. difficile. Risk factors for infection included ward location and stool incontinence. Age, body‐mass index ≤18 kg/m2, and diagnoses of dementia and pressure sores tended to be associated with infection, but not significantly. Early mortality rates did not differ, but 12‐month mortality for the infected patients was higher (83% vs 50%, P = .05). Therefore, we conclude that postantibiotic C. difficile infection serves as a marker of death in nursing‐home patients, one that can be differentiated from the risk of antibiotic treatment alone. This increased death rate may be related in part to clinically unrecognized pseudomembranous colitis or, alternatively, to absorption of C. difficile toxins or even endotoxin from the gut lumen into the systemic circulation.
Infectious disorders drug targets, Jun 1, 2007
The Journal of Infectious Diseases, Jul 1, 1983
An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to toxins A and B of... more An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to toxins A and B of Clostridium difficile was developed. Serum samples from 340 patients were tested for determination of the age-related prevalence of antitoxin. Antibody to toxin A was present in 64% of patients more than two years old and antibody to toxin B in 66% of patients more than six months old. A strongly positive ELISA value correlated with the presence of cytotoxicity-neutralizing antibody (P less than 0.001). Strongly positive ELISA values were obtained more commonly in convalescent sera from 16 patients with C difficile-induced colitis than in sera from the control population (antibody to toxin A, P less than 0.05; antibody to toxin B, P less than 0.001). Testing of paired sera revealed significant increases in the titer of IgG antibody to toxin A or B. Ten of the 16 patients with colitis had IgM titers of greater than or equal to 1:160 to one or both toxins. The data presented suggest that antibodies to toxins A and B are present in the majority of older children and adults and that patients with C difficile-induced disease develop serologic responses to one or both toxins.
International journal of systematic bacteriology, Apr 1, 1976
In 1971, Strength and Krieg reported the isolation of a gram-negative freshwater rod which exhibi... more In 1971, Strength and Krieg reported the isolation of a gram-negative freshwater rod which exhibited bipolar flagellar fascicles clearly visible by dark-field microscopy. The flagellar fascicles exhibited helical wave propagation, basal bending, and an ability to coil up like springs. Despite the flagellar activity, the cells were apparently unable to swim freely. Such organisms appeared to be similar morphologically to an organism previously described by Houwink in 1953 and Jarosch in 1969. The present report describes a reliable isolation method for such organisms based on the use of L-proline and semisolid agar. Upon isolation, the organisms grew in flocs, from which a highly viscous matrix could be separated by high-speed centrifugation. After many transfers, the growth gradually became homogeneous and turbid, and the viscous substance could no longer be demonstrated. Under certain conditions of growth, steady straight-line motility could be observed and photographed within viscous flocs. Straight-line, free-swimming motility occurred in viscous suspensions of cells prepared by homogenization of flocs. In 8-to 12-hold cultures in the nonviscous homogeneous condition, some cells could swim slowly in irregular, circular paths; other could move about on surfaces. When the viscosity of the medium was increased, nearly every cell could swim freely and steadily in straight paths. A viscosity of 200 centipoise was optimal for strain XI, whereas 10 centipoise was optimal for strains X and XU. These results suggest that the organisms may be highly adapted to life within viscous flocs. The organism exhibited nitrogenase activity when tested by methods developed by Dobereiner and her colleagues for "Spirillum" lipoferum; Aquaspirillum peregrinum also was found to possess nitrogenase activity. Investigation of the physiology and deoxyribonucleic acid base composition of strains X, XI, and XI1 has indicated that even though the organisms are straight rods, they are probably members of the genus Aquaspirillum. Important taxonomic considerations include: coccoid body or "microcyst" formation, possession of a "polar membrane" similar to that occurring in certain spirilla, bipolar tufts of flagella, a strictly respiratory metabolism, inability to attack carbohydrates, positive catalase and oxidase reactions, and a deoxyribonucleic acid base composition of 62 to 65 mol% guanine plus cytosine. The organisms were assigned to a new species, Aquaspirillum fasciculus, and the type strain was deposited with the American Type Culture Collection under the number 27740. In 1953, Houwink (11) described a "rod-like" bacterium which exhibited a "floundering" rather than a swimming type of motility. In resting specimens, both bipolar flagellar fascicles had the form of a coiled spring. The cells seldom moved more than a cell length, but in
Journal of Clinical Microbiology, Feb 1, 1982
Rapid colorimetric tests for trypsin and a-glucosidase are described for use in the identificatio... more Rapid colorimetric tests for trypsin and a-glucosidase are described for use in the identification of Bacteroides gingivalis from dental plaque. Coykendall et al. (1) have recently proposed a new species, Bacteroides gingivalis, which consists of strains previously classified as Bacteroides asaccharolyticus. These organisms are found in the human oral environment, especially in patients with periodontal disease (5). They show little DNA-DNA homology with the type strain of B. asaccharolyticus (1), fail to react with a commercial fluorescent antibody prepared against B. asaccharolyticus (6; S. A. Syed, B. E. Laughon, and W. J. Loesche. Abstr. Annu. Meet. Am. Soc. Microbiol. 1980, C26, p. 279), and produce phenylacetic acid as an end product (3). Furthermore, we have found that they produce a unique proteolytic activity which resembles the activity of trypsin and which differentiates them from B. asaccharolyticus, Bacteroides melaninogenicus subsp. intermedius, and Bacteroides melaninogenicus subsp. melaninogenicus. B. gingivalis hydrolyzes N-benzoyl-DL-arginine-2-naphthylamide (BANA), a substrate commonly used to assay trypsin activity, and fails to hydrolyze p-nitrophenyl-a-glucoside (PNPG), a substrate used to assay a-glucosidase activity. We first observed these activities in testing the API ZYM system (Analytab Products, Plainview, N.Y.) for the rapid identification of gram-negative bacteria present in periodontal disease (4a). The API ZYM system consists of 19 enzyme reaction mixtures containing chromogenic substrates. Although we found this system to be very convenient and reliable, the rather high cost prohibited its use on a routine basis. We have, therefore, adapted the most important differential reactions (trypsin and a-glucosidase) for individual testing in a miniaturized system.
Journal of Periodontology, Apr 1, 1982
Plaque samples from 22 ulcerated sites in eight patients with ANUG were cultured using quantitati... more Plaque samples from 22 ulcerated sites in eight patients with ANUG were cultured using quantitative anaerobic procedures and were examined microscopically. The partial characterization of the predominant cultivable flora revealed a constant flora comprised of a limited number of bacterial types and a variable flora composed of a heterogeneous array of bacterial types. This constant flora would appear to be pathognomonic of acute necrotizing ulcerative gingivitis (ANUG) and included the various Treponema and Selenomonas sp., which comprised about 32 and 6%, respectively, of the microscopic count; B. melaninogenicus ssp. intermedius and Fusobacterium sp., which averaged 24 and 3%, respectively, of the viable count. One week of metronidazole treatment caused a prompt resolution of clinical symptoms, which coincided with a significant reduction in the plaque proportions of the Treponema sp., B. melaninogenicus ssp., intermedius and Fusobacterium sp. for at least 2 to 3 months following treatment. Thus, the same anaerobic species which were numerically associated with the ANUG lesion were also selectively reduced in the plaque flora following resolution of the infection. This supports a role for the above species in the ulcerative stage of the lesion but does not demonstrate that these specific anaerobes initiated the infection. Although not confirmed by the data, it was proposed that these particular anaerobic species gained ascendency in the plaque as a result of being selected through the availability of host-derived nutrients in individuals who had undergone certain physiological and psychological stresses.
Journal of Bacteriology, Sep 1, 1974
Aquaspirillum (Spirillum) gracile is one of the few spirilla that cause acidification of the medi... more Aquaspirillum (Spirillum) gracile is one of the few spirilla that cause acidification of the medium when cultured with sugars. Acidic reactions have been reported only for D-glucose, D-galactose, and L-arabinose, and the mode of attack of these sugars has not been previously investigated. The soluble portion of extracts of glucose-cultured cells of A. gracile ATCC 19624 was found by spectrophotometric methods to contain enzyme activities characteristic of the Entner-Doudoroff and Embden-Meyerhof-Parnas pathways. No activity for 6-phosphogluconate dehydrogenase (EC 1.1.1.44) was detected. Pyridine nucleotide-linked dehydrogenase activities for L-arabinose and D-galactose (EC 1.1.1.46 and EC 1.1.1.48) occurred in the soluble fraction of cells cultured with either sugar. Glucose-cultured cells contained not only glucokinase (EC 2.7.1.2) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) activities but also glucose dehydrogenase (EC 1.1.1.47) activity. Enzymes capable of oxidizing gluconate were not detectable, but gluconokinase (EC 2.7.1.12) activity was present. Paper chromatographic analysis of the spent culture supernatant media from glucosecultured cells indicated an accumulation of gluconic acid, and this was confirmed by enzymatic methods. Evidence is presented for the production of D-galactonic and L-arabonic acids in cultures containing D-galactose or L-arabinose, respectively.
Nutrition Today, Nov 1, 1996
Background: Clostridium difficile infection (CDI) has become a global concern over the last decad... more Background: Clostridium difficile infection (CDI) has become a global concern over the last decade. In the United States, CDI escalated in incidence from 1996 to 2005 from 31 to 64/100,000. In 2010, there were 500,000 cases of CDI with an estimated mortality up to 20,000 cases a year. The significance of this problem is evident from the hospital costs of over 3 billion dollars annually. Fecal microbiota transplant (FMT) was first described in 1958 and since then about 500 cases have been published in literature in various small series and case reports. This procedure has been reported mainly from centers outside of the United States and acceptance of the practice has been difficult. Recently the US Food and Drug Administration (FDA) labeled FMT as a biological drug; as a result, guidelines will soon be required to help establish it as a mainstream treatment. More US experience needs to be reported to popularize this procedure here and form guidelines. Method: We did a retrospective review of our series of patients with relapsing CDI who were treated with FMT over a 3-year period. We present our experience with FMT at a community hospital as a retrospective review and describe our procedure. Results: There were a total of 12 patients who underwent FMT for relapsing C. difficile. Only one patient failed to respond and required a second FMT. There were no complications associated with the transplant and all patients had resolution of symptoms within 48 hours of FMT. Conclusion: FMT is a cheap, easily available, effective therapy for recurrent CDI; it can be safely performed in a community hospital setting with similar results.
Current Topics in Medicinal Chemistry, Mar 1, 2007
Over the past 50 years, no new drug classes have been introduced to treat tuberculosis. Tuberculo... more Over the past 50 years, no new drug classes have been introduced to treat tuberculosis. Tuberculosis (TB) kills nearly two million people a year mainly in the poorest communities in the developing world. It afflicts millions more. About one third of the world&amp;amp;amp;amp;#39;s population is silently infected with TB that may erupt into disease with increased age or suppression of the immune system. Nearly nine million new active cases develop every year. The World Health Organization (WHO) declared the disease a global emergency as long ago as 1993. Although huge efforts in public health control have reduced the disease burden within most established market economies, in Africa and Asia the epidemic continues to accelerate, particularly fueled by the HIV epidemic. Furthermore, resistance to the standard drugs isoniazid and rifampicin is increasing worldwide. Since the 1990s, mycobacteria have emerged with resistance patterns rendering all currently available antibiotics ineffectual. The pharmaceutical industry has mostly abandoned TB drug development due to perceived non-profitable consumer market and the diminishing number of companies engaged in anti-infective research. The public sector and infectious disease researchers have responded to advance fundamental science and to create new chemical entities as early drug candidates. With support from research funding agencies, philanthropic donors, and the STOP-TB Partnership, new chemical tools and new approaches to effectively implement TB control programs are evolving. Advanced preclinical development and strategies for Phase III clinical trials remain gap areas that will require additional engagement from all sectors.
The Lancet, Jun 1, 1989
A commercially available radial immunodiffusion assay was used to measure serum alpha-1-antitryps... more A commercially available radial immunodiffusion assay was used to measure serum alpha-1-antitrypsin levels in stool samples from subjects aged over 60 years as a marker of protein-losing enteropathy. alpha 1-antitrypsin was found in all of 12 patients with colonoscopy-confirmed pseudomembranous colitis, 6 of 14 (43%) patients with Clostridium difficile diarrhoea without pseudomembranes, 6 of 12 (50%) nursing-home patients culture-positive for Cl difficile but negative for its cytotoxin, and none of 15 healthy control subjects. It is concluded that serum protein loss into the gastrointestinal tract can occur as a result of Cl difficile infection, that its presence correlates with the severity of disease, and that it may occur even in the absence of diarrhoea. The diagnosis of protein-losing enteropathy should be considered for all patients with Cl difficile infection, particularly elderly nursing-home patients, in whom the risk of Cl difficile disease and the frequency of severe malnutrition are high.
Antimicrobial Agents and Chemotherapy, Oct 1, 1986
Fifty volunteers randomly assigned to one of five hand washing agents (10 subjects per agent)-a n... more Fifty volunteers randomly assigned to one of five hand washing agents (10 subjects per agent)-a nonantiseptic liquid soap (control), an antiseptic hand rinse containing 60% isopropyl alcohol (IPA) with emollients (Alc A), an antiseptic hand rinse containing 70% IPA and 0.5% chlorhexidine gluconate with emollients (Alc B), an antiseptic containing 4% chlorhexidine gluconate and 4% IPA (CHG), and 70% IPAwashed their hands 15 times per day for 5 days under supervision by using a standardized technique and measured amounts of test agent. Microbiologic samples of hand flora were obtained at base line and after hand washes 1 and 15 on test days 1 and 5. After the initial hand wash there were significant reductions over base line in aerobic and anaerobic log CFU among those using Alc A, CHG, and IPA. By the end of the first day of hand washing (15 washes), there were 2-log or greater reductions in aerobic counts among subjects using all antiseptics, but no significant reductions in controls. By the end of day 5, all agents produced significant reductions in aerobic (P = 0.0002) and anaerobic (P = 0.002) counts over control soap. Subject assessment of effects of hand washing on the skin and overall satisfaction varied significantly by product (P = 0.04 and 0.05, respectively). We conclude that alcohol-based hand rinses are highly efficacious, and such products are recommended as a health care personnel hand wash, particularly when sink and running water are inaccessible.
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Papers by Barbara Laughon