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In the past decade, there was increased research interest in studying internal motions of flexible proteins in solution using Neutron Spin Echo (NSE) as NSE can simultaneously probe the dynamics at the length and time scales comparable to protein domain motions. However, the collective intermediate scattering function (ISF) measured by NSE has the contributions from translational, rotational, and internal motions, which are rather complicated to be separated. Widely used NSE theories to interpret experimental data usually assume that the translational and rotational motions of a rigid particle are decoupled and independent to each other. To evaluate the accuracy of this approximation for monoclonal antibody (mAb) proteins in solution, dissipative particle dynamic computer simulation is used here to simulate a rigid-body mAb for up to about 200 ns. The total ISF together with the ISFs due to only the translational and rotational motions as well as their corresponding effective diffusion coefficients is calculated. The aforementioned approximation introduces appreciable errors to the calculated effective diffusion coefficients and the ISFs. For the effective diffusion coefficient, the error introduced by this approximation can be as large as about 10% even though the overall agreement is considered reasonable. Thus, we need to be cautious when interpreting the data with a small signal change. In addition, the accuracy of the calculated ISFs due to the finite computer simulation time is also discussed., (© 2021 Author(s).)

We present experiments and simulations that show a fundamental scaling for both the rheology and microstructure of flowing gels. Unique flow-SANS measurements demonstrate that the structure orients along both the neutral and compression axis. We quantify the anisotropy using a single parameter, α, that scales by a dimensionless number, M^{'}, that arises from a force balance on a particle. Simulations support the scalings and confirm the results are independent of the shape and range of the potential suggesting a universal for colloidal gels with short-ranged attractions.

The stress propagation in a concentrated attractive colloidal suspension under shear is studied using numerical simulations. The spatial correlations of the intercolloidal stress field are studied and an inertia-like tensor is defined in order to characterize the anisotropic nature of the stress field. It is shown that the colloids remain in a liquid order, the intercolloidal stress is strongly anisotropic. A transition under flow is observed: during a transient regime at low deformation, the stress propagates along the compression direction of the shear, whereas at larger deformations, the stress is organized into layers parallel to the (flow, vorticity) plane.

Background: Vancomycin-resistant Enterococcus (VRE) colonization of the gastrointestinal tract shares similar risk factors with Clostridium difficile infection. We sought to elucidate the prevalence and risk factors of VRE colonization associated with C difficile infection., Methods: All adult inpatients with C difficile infection from July 2006 to October 2006 were prospectively evaluated. All C difficile toxin-positive stool samples were screened for detection of VRE. Risk factors for VRE colonization were compared in patients with C difficile infection with and without VRE colonization., Results: Of the 158 cases of C difficile infection evaluated, 88 (55.7%) involved VRE colonization. Independent risk factors for VRE colonization were admission from long-term care facilities (P = .013), dementia (P = .017), and hospitalization in the previous 2 months (P = .014). No statistically significant difference between C difficile infection cases with and without VRE colonization in terms of previous receipt (within 1 month) of antibiotics, including metronidazole and vancomycin, was found on multivariate analysis. C difficile infection cases with VRE colonization had a higher prevalence of coinfection with methicillin-resistant Staphylococcus aureus (P = .002) and Acinetobacter spp (P = .006)., Conclusion: VRE colonization was associated with >50% of C difficile infection cases and with a higher rate of coinfection with multidrug-resistant pathogens. Given the high rate of C difficile infection associated with VRE colonization, active surveillance of VRE in patients with C difficile infection is reasonable in high-risk settings., (Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.)

Objective: To compare 8 severity score indices for Clostridium difficile infection (CDI)., Design: Prospective observational study., Methods: This study was conducted from July through October 2006. All hospitalized patients in 3 university-affiliated hospitals with a positive fecal Clostridium difficile toxin assay result were evaluated. Infection was considered severe if patients had at least 1 of the following clinical events during their hospitalization: (1) death attributed to CDI within 30 days after diagnosis, (2) colectomy necessitated by CDI, or (3) intensive care unit admission for management of complications attributed to CDI. Severity was assessed on the basis of 8 severity score indices, using published criteria for severe CDI as the benchmark. The 8 severity score indices studied were Beth Israel, University of Pittsburgh Medical Center version 1, University of Pittsburgh Medical Center version 2, Hines VA, modified University of Illinois, University of Calgary version 1, University of Calgary version 2, and University of Temple., Results: Of 184 patients with CDI evaluated, 19 had severe cases and 165 had nonsevere cases, as assessed on the basis of the defined severe CDI criteria. Sensitivities of the 8 severity score indices studied ranged from 63.2% to 84.2%, and specificities ranged from 59.4% to 93.9%. The Hines VA index had the highest kappa score (0.69 [95% confidence interval, 0.54-0.83]), followed by the University of Pittsburgh Medical Center version 1 index. Independent risk factors for severe CDI determined by multivariate analysis were abdominal distention (P = .007), fever (temperature, 38.0°C or above; P = .042), white blood cell count of at least 20,000 cells/mm(3) (P = .035), and hypoalbuminemia (serum albumin level less than 3 mg/dL; P = .029)., Conclusion: The Hines VA CDI severity score index appeared to display the strongest correlation for predicting more severe forms of CDI.

This is the third in a series of articles that describe, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing, visualization, and machine learning to accelerate scientific discovery. In this article we focus on the use of high performance computing and visualization for simulations of nanotechnology.

We report a case of endocarditis due to a penicillin-"resistant" Streptococcus parasanguinis, discuss interpretations of the American Heart Association's guidelines for the treatment of viridans group streptococcal infection, and comment on therapy for infective endocarditis due to penicillin-resistant viridans group streptococci.

This is the second in a series of articles describing a wide variety of projects at NIST that synergistically combine physical science and information science. It describes, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing, visualization, and machine learning to accelerate research. The examples include scientific collaborations in the following areas: (1) High Precision Energies for few electron atomic systems, (2) Flows of suspensions, (3) X-ray absorption, (4) Molecular dynamics of fluids, (5) Nanostructures, (6) Dendritic growth in alloys, (7) Screen saver science, (8) genetic programming.

Disease-specific registries have many important applications in epidemiologic, clinical and health services research. Since 1989 the Department of Veterans Affairs has maintained a national HIV registry. VA's HIV registry is national in scope, it contains longitudinal data and detailed resource utilization and clinical information. To describe the structure, function, and limitations of VA's national HIV registry, and to test its accuracy and completeness. The VA's national HIV registry contains data that are electronically extracted from VA's computerized comprehensive clinical and administrative databases, called Veterans Integrated Health Systems Technology and Architecture (VISTA). We examined the number of AIDS patients and the number of new patients identified to the registry, by year, through December 1996. We verified data elements against information obtained from the medical records at five VA sites. By December 1996, 40,000 HIV-infected patients had been identified to the registry. We encountered missing data and problems with data classification. Missing data occurred for some elements related to the computer programming that creates the registry (e.g., pharmacy files), and for other elements because manual entry is required (e.g., ethnicity). Lack of a standardized data classification system was a problem, especially for the pharmacy and laboratory files. In using VA's national HIV registry we have learned important lessons, which, if taken into account in the future, could lead to the creation of model disease-specific registries.

The rate of scientific discovery can be accelerated through computation and visualization. This acceleration results from the synergy of expertise, computing tools, and hardware for enabling high-performance computation, information science, and visualization that is provided by a team of computation and visualization scientists collaborating in a peer-to-peer effort with the research scientists. In the context of this discussion, high performance refers to capabilities beyond the current state of the art in desktop computing. To be effective in this arena, a team comprising a critical mass of talent, parallel computing techniques, visualization algorithms, advanced visualization hardware, and a recurring investment is required to stay beyond the desktop capabilities. This article describes, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing and visualization to accelerate condensate modeling, (2) fluid flow in porous materials and in other complex geometries, (3) flows in suspensions, (4) x-ray absorption, (5) dielectric breakdown modeling, and (6) dendritic growth in alloys.

The Message Passing Interface (MPI) is the de facto standard for writing parallel scientific applications in the message passing programming paradigm. Implementations of MPI were not designed to interoperate, thereby limiting the environments in which parallel jobs could be run. We briefly describe a set of protocols, designed by a steering committee of current implementors of MPI, that enable two or more implementations of MPI to interoperate within a single application. Specifically, we introduce the set of protocols collectively called Interoperable MPI (IMPI). These protocols make use of novel techniques to handle difficult requirements such as maintaining interoperability among all IMPI implementations while also allowing for the independent evolution of the collective communication algorithms used in IMPI. Our contribution to this effort has been as a facilitator for meetings, editor of the IMPI Specification document, and as an early testbed for implementations of IMPI. This testbed is in the form of an IMPI conformance tester, a system that can verify the correct operation of an IMPI-enabled version of MPI.

Purpose: To assess the severity of constitutional symptoms in persons with human immunodeficiency virus (HIV) infection, and their relationship to health-related quality of life (HRQOL)., Patients and Methods: Two hundred five HIV-infected patients (93% male, 26% African American, 28% Latino, 39% white, 7% other ethnicity) with diarrhea, fever, or weight loss were studied at a county hospital and a Veterans Administration hospital in southern California. Consenting subjects were administered a battery that included 11 scales measuring various aspects of health-related quality of life and detailed questions about six constitutional symptoms or symptom complexes (myalgias, exhaustion, anorexia/nausea/vomiting, night sweats, fever, and weight loss) as well as about other manifestations of HIV disease., Results: Constitutional symptoms except weight loss were all strongly related to all measures of quality of life. On 0 (worst) to 100 (best) point scales, mean scores ranged from 34 (for individuals having all five symptoms other than weight loss) to 78 (for those with none) for physical function, 43 to 79 for emotional well-being, and 36 to 73 for social function. Adjustment for helper T-lymphocyte counts, duration of illness, and demographic characteristics did not diminish these associations., Conclusion: The presence, number, and severity of constitutional symptoms in HIV disease is strongly related to health-related quality of life in symptomatic HIV-infected individuals. Identifying and treating these very common symptoms has the potential to improve quality of life in these patients.

Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies).

The objective of the present study was to assess the association between type of health insurance coverage and use of diagnostic tests and therapies among patients with AIDS-related Pneumocystis carinii pneumonia (PCP). Fifty-six private, public, and community hospitals in Chicago, Los Angeles, and Miami were selected for the study, and the charts of 890 patients with empirically treated or cytologically confirmed PCP, hospitalized during 1987 to 1990 were retrospectively reviewed. Patients were classified by insurance status: self-pay (n = 56), Medicaid (n = 254), or private insurance, including health maintenance organizations and Medicare (n = 580). Primary outcomes were the use and timing of bronchoscopy, the type and timing of PCP therapy, and in-hospital mortality. The results indicate that Medicaid patients were less likely than privately insured patients to undergo bronchoscopy (relative odds = 0.61; 95% CI = 0.40, 0.93; p = 0.02) or to have their diagnosis of PCP confirmed (relative odds = 0.51; 95% CI = 0.33, 0.77), after adjusting for patient, severity of illness, and hospital characteristics. Medicaid patients were approximately three-fourths more likely than privately insured patients (relative odds = 1.73; 95% CI = 1.01, 2.96; p = 0.04) to die in-hospital, after adjusting for patient, severity of illness, and hospital characteristics. However, with further adjustment for confirmation of PCP, Medicaid patients no longer had a significantly higher likelihood of dying in-hospital. We conclude that Medicaid patients are less likely to receive diagnostic bronchoscopy than privately insured or self-insured patients, more likely to be empirically treated for PCP, and more likely to die in-hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Many patients infected with the human immunodeficiency virus (HIV) with symptoms suggestive of pneumonia are treated empirically for Pneumocystis carinii pneumonia (PCP), although other bacterial infections (e.g., tuberculosis) and pulmonary Kaposi's sarcoma may cause identical symptoms. Empiric treatment for PCP may result in misdiagnosis and mistreatment. When the outcomes of cytologically confirmed versus empirically treated PCP cases were evaluated, the most important predictors of in-hospital mortality were severity of illness and use of bronchoscopy. Persons who did not undergo bronchoscopy had higher mortality rates than patients negative by bronchoscopy or cytologically confirmed as positive for PCP (22% vs. 11% vs. 14%, P < .01), although severity of illness and timing of anti-PCP medications did not differ significantly. Compared with cytologically confirmed cases, persons who did not have bronchoscopy were more likely to die than were bronchoscopy-negative patients (P < .05), after adjusting for severity of illness. Bronchoscopy use may have contributed to better outcomes for persons treated for HIV-related PCP.

Pneumocystis carinii pneumonia (PCP) has been the most common reason for hospitalization and the most common cause of death for persons with HIV infection. Hospital mortality rates for PCP range from 10 to 60%. Studies that evaluate differences in hospital mortality rates must control for differences in patient severity of illness. We developed a simple staging system for categorizing severity of illness in patients with PCP. We analyzed the relation between clinical factors and in-hospital mortality for 576 hospitalized patients with HIV-related PCP treated at 56 hospitals for the years 1987 to 1990. Four stages of PCP could be identified based on three routinely measured clinical variables: alveolar-arterial oxygen difference, total lymphocyte count, and body mass index. The mortality rate increased by stage: 1% for Stage 1, 8% for Stage 2, 23% for Stage 3, and 48% for Stage 4. The four-stage severity system compared well with previous models developed for AIDS and for PCP, and is easier to use in clinical practice. Our staging system identifies patients with a high and low risk of in-hospital death upon admission. Physicians may benefit from consideration of PCP stage in deciding on management strategies. In addition, researchers involved in clinical trials of new agents for PCP might consider stratification by PCP stage in order to define homogenous groups.

Background: Zidovudine is recommended for asymptomatic and early symptomatic human immunodeficiency virus (HIV) infection. The best time to initiate zidovudine treatment remains uncertain, however, and whether early treatment improves survival has not been established., Methods: We conducted a multicenter, randomized, double-blind trial that compared early zidovudine therapy (beginning at 1500 mg per day) with late therapy in HIV-infected patients who were symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy initially received placebo and began zidovudine when their CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired immunodeficiency syndrome (AIDS) developed., Results: During a mean follow-up period of more than two years, there were 23 deaths in the early-therapy group (n = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen. Early therapy was associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas late therapy was associated with more skin rash., Conclusions: In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.

Plesiomonas shigelloides, when grown in an iron-poor medium (syncase), produces a substances that causes elongation of Chinese hamster ovary (CHO) cells similar to that produced by cholera toxin. When syncase is supplemented with iron, the ability of P. shigelloides (but not of Vibrio cholerae) to produce this elongation of CHO cells is lost. Iron depletion of the growth medium appears to be essential for the CHO cell elongation produced by P. shigelloides but is not essential for the production of toxin by V. cholerae. The possible role of iron regulation of this potential virulence factor warrants further study.

Motile Aeromonas spp. are said to have an optimal growth temperature of 28 degrees C. We performed growth studies on 24 isolates at 29 and 37 degrees C and found that the optimal growth temperature was not necessarily 28 degrees C. We also detected temperature-dependent differences in soluble protein production in some of these strains.

We have reviewed the incidence of Aeromonas in patients with enteric disease at our hospital and found it to be the highest of any potential enteric pathogen. Eighty adult patients with diarrhea had Aeromonas isolated from feces, and in 73 Aeromonas was the only potential bacterial or parasitic pathogen detected. The spectrum of illness in patients with Aeromonas-related diarrhea ranged from acute, self-limited diarrhea to a chronic, indolent diarrheal illness. Sixteen percent (13/80) of the patients had evidence of colitis noted during sigmoidoscopy or colonoscopy. Our data (and those from other studies) indicate that Aeromonas is relatively common in the feces of adults with diarrhea; they also indicate the need for prospective, controlled clinical and bacteriological studies to determine whether or not Aeromonas is an important enteric pathogen in adults.

Clostridium difficile has been shown to be a cause of antimicrobial agent-associated diarrhea and colitis. The source from which this organism gains access to the gastrointestinal tract is not known. Cultures of the hospital environments of six of eight patients whose fecal cultures were positive for C. difficile yielded this organism, whereas cultures of control hospital sites were almost invariably negative. These data suggest that hospital environmental contamination may be a potential source of infection. Further studies are needed to determine the role of various possible sources of C. difficile in human diarrheal disease.

Although antimicrobial agent-associated colitis has been recognized as a clinicopathologic entity for years, the cause of this disease has been determined only recently. Virtually all cases of pseudomembranous colitis and some cases of antimicrobial agent-associated nonspecific colitis or diarrhea have been shown to be caused by a toxin of Clostridium difficile. Methods for cultivating C difficile from feces and for detecting the toxin have been developed. Oral administration of vancomycin has proved to be effective for the treatment of C difficile-induced colitis, although isolated instances of relapse after treatment have been documented.The discovery of C difficile as a human intestinal pathogen has provided an explanation for some, but not all cases of antimicrobial agent-associated diarrhea. The epidemiology, pathogenesis and means of prevention of C difficile toxin-induced diarrhea remain to be determined.

Malassezia furfur, a lipophilic yeast that is the etiologic agent of tinea versicolor, has not been considered as a cause of serious illness in adults in the past. Two adults are described in whom Malassezia furfur fungemia developed while receiving total parenteral nutrition supplemented with lipids. The organism was identified in blood cultures from both patients only after isolation media were supplemented with a source of fatty acids. Because M. furfur will grow only in media supplemented with fatty acids, clinicians should alert the laboratory whenever a lipophilic organism is suspected to be present in blood cultures.

Clostridium difficile is a recognized cause of pseudomembranous (antimicrobial agent-associated) colitis and may be one of the causes of antimicrobial agent-induced diarrhea. A selective and differential agar medium that contains cycloserine, cefoxitin, fructose, and egg yolk (CCFA) was developed to facilitate the isolation of C. difficile from fecal specimens. Quantitative cultures of 16 stock strains of C. difficile on this medium (and on a medium containing cycloserine, fructose, and egg yolk) yielded counts equivalent to those obtained on blood agar; other media selective for clostridia, including Clostrisel agar, reinforced clostridial agar plus 0.2% para-cresol, and egg yolk-neomycin agar (the latter was inoculated with cultures subjected to prior heat shocking), were also tested and found to be inhibitory to the growth of C. difficile. Of 28 fecal or colostomy effluent specimens cultured on the above media, 14 yielded C. difficile. CCFA was found to be the most sensitive and selective of these media for the recovery of C. difficile. Colonies of C. difficile growing on CCFA had distinctive morphological and fluorescent properties which were sufficient for presumptive identification. CCFA should provide a rapid method for the screening of fecal specimens from patients with antimicrobial agent-associated diarrhea or colitis for C. difficile.

Spirochetes were isolated from the feces of 11 homosexual males who had diarrhea. The anaerobic organisms were isolated from a selective medium that consisted of Trypticase soy agar supplemented with either 5% horse or human blood, 400 micrograms of spectinomycin per ml, and 5 micrograms of polymyxin B per ml. Nonselective media that permitted good growth of these fastidious organisms were developed, and selected biochemical tests were performed. The tests included carbohydrate utilization, detection of certain enzymes, and determination of volatile fatty-acid end products of metabolism. Two growth patterns were noted on solid media, a haze of growth and production of small colonies. Based on the results of biochemical tests, patterns of preformed enzymes, and volatile fatty-acid production, we believe that the 11 isolates represent a heterogeneous group of spirochetes. The data suggest that the human colon may harbor unique strains of cultivable spirochetes; additional study of the taxonomy of the organisms and assessment of their virulence for humans are needed.

The efficacy and safety of ceftizoxime and cefoxitin were compared in a randomized, double-blind study of therapy for lower extremity infections in patients with diabetes mellitus or peripheral vascular disease. Overall clinical responses were satisfactory in 82% (23/28) of patients treated with ceftizoxime and in 68% (17/25) of patients treated with cefoxitin. The difference was not statistically significant. Ceftizoxime had superior in vitro activity against Enterobacteriaceae, especially Enterobacter cloacae, whereas cefoxitin had better activity against the Bacteroides fragilis group. Relapses of infection were common in both groups during long-term follow-up; only about one third of patients in either group maintained satisfactory outcomes after one year. More than half of the patients in both groups responded to one or more courses of medical therapy and avoided major amputations for one year following entry into the study.

Plesiomonas shigelloides was thought to be the cause of diarrhea in six patients seen in Los Angeles. Although this organism is considered to be a cause of diarrhea in the Orient, it has infrequently been noted to be associated with diarrhea in North America.

The in vitro activities of 17 antimicrobial agents were evaluated against 46 clinical isolates of formate/fumarate-requiring anaerobic gram-negative bacilli. Strains of Bacteroides ureolyticus (23) were almost uniformly susceptible to the tested antimicrobials, whereas strains of Bacteroides gracilis (18) showed some striking resistance with penicillin active against only 67%, the cephalosporins active against 67%-89%, and clindamycin active against 67%. Although few strains of Wolinella species/C. concisus (5) were available for testing, these isolates tended to be more resistant than B. ureolyticus but less resistant than B. gracilis.

A total of 49 anaerobic and 52 aerobic or facultative bacteria were tested for their susceptibilities to clindamycin and ceftazidime alone and in combination. Synergy was noted for 11 strains, whereas antagonism was not detected. The combination of clindamycin and ceftazidime may prove to be useful for the treatment of severe mixed infections caused by anaerobes and aerobes or facultative bacteria.

Legionnaires' disease is reported in five renal-transplant recipients. All had febrile respiratory illnesses with pulmonary infiltrates and one died. The diagnosis was made on clinical features and by indirect fluorescent antibody titres. Symptoms started after maximum immunosuppressive therapy.

We report a case of fungemia and disseminated disease caused by a urease-negative strain of Cryptococcus neoformans in a patient with the acquired immune deficiency syndrome. Except for failure to hydrolyze urea, the microbiological characteristics of the isolate were typical of C. neoformans. Laboratory specialists should be aware of the occurrence of atypical strains of C. neoformans, particularly those recovered from patients with the acquired immune deficiency syndrome.

We have noted that prairie dogs given cefoxitin develop diarrhea and lose weight yet survive for periods of up to 4 weeks. Therefore, we tested the hypothesis that cefoxitin causes Clostridium difficile cecitis in prairie dogs. Six prairie dogs were given a single intramuscular dose of 100 mg of cefoxitin per kg of body weight, and six control animals received saline; both groups were sacrificed 1 week later. Controls had no diarrhea and lost 2% of their body weight, whereas cefoxitin-treated animals had diarrhea (P less than 0.001) and lost 16% of their body weight (P less than 0.001); one animals died 6 days after cefoxitin challenge. None of the controls yielded C. difficile or had cecal cytotoxin or pseudomembranes detected. Cecal contents from all cefoxitin-treated animals, however, yielded C. difficile (P less than 0.01) and had cecal cytotoxin present (P less than 0.01). Four of five surviving animals also had cecal pseudomembranes present (P less than 0.01). These results demonstrate that in prairie dogs cefoxitin induces C. difficile cecitis. We conclude that the prairie dog is another model for the study of antibiotic-induced diarrhea. The disease in prairie dogs may have a more chronic course than in other animal models of C. difficile-induced diarrhea and may be useful as a model for studying certain aspects of C. difficile-induced diarrhea.

A new species of Legionella that caused pneumonia in a patient with chronic lymphocytic leukemia has been characterized. The Legionella wadsworthii species nova is proposed for this bacterium. The type strain is Wadsworth 81-716A (American Type Culture Collection 33877). The new species differs phenotypically from L. pneumophila in that the predominant cellular fatty acid is methyl-12-methyltetradecanoic acid (a-15:0) rather than methyl-14-methylpentadecanoic acid (i-16:0), and in its failure to react with L. pneumophila antiserum. The clinical illness caused by L. wadsworthii was not apparently different from that seen with other legionella infections, except for prolonged fever and slow resolution of pulmonary infiltrates.

Virulence of several species of enteropathogenic bacteria has been correlated with the ability of isolates to take up the dye Congo red. To determine whether Congo red uptake might be a useful marker for virulence of motile Aeromonas species, we examined 50 strains of diverse clinical origin on a medium containing 50 micrograms of Congo red per ml. All of the strains took up the dye to various degrees. For most strains, uptake was greatest at 37 degrees C and least at 22 degrees C. Production of acetyl methyl carbinol (Voges-Proskauer test) or lysine decarboxylase has been reported by some investigators to be a virulence marker for Aeromonas species. Congo red uptake did not correlate with either acetyl methyl carbinol or lysine decarboxylase production in our study. These data suggest that Congo red uptake may not be a useful marker for virulence of motile Aeromonas species.

Clostridium difficile was isolated from the faeces of a patient with clindamycin-associated pseudomembranous colitis (P.M.C.). The presence of a preformed faecal toxin and the toxigenicity of both the faecal isolate of C. difficile and a reference strain of C. difficile were demonstrated by tissue-culture assay. The toxin of both strains of C. difficile and that in the patient's faeces were neutralised by heating and by incubation with antitoxin to C. sordellii, but not by incubation with antitoxin to C. histolyticum, C. oedematiens (novyi), C. welchii (C. perfringens) or C. septicum. These data implicate the toxin of C. difficile as a major, and perhaps the sole, cause of antimicrobial-agent-associated P.M.C. of man and suggest that the neutralisation of the faecal toxin of P.M.C. by C. sordellii antitoxin, as described by other investigators, may be a non-specific phenomenon.

In the late 1970s it was found that Clostridium difficile causes a lethal, clindamycin-induced ileocecitis in the Syrian hamster; this animal model has been an invaluable aid to our understanding of antimicrobial agent-induced diarrhea in humans. C. difficile is involved in almost all cases of pseudomembranous colitis and in approximately one-fourth of cases of antimicrobial agent-associated diarrhea in humans in which a pseudomembrane is not detected. The presenting signs and symptoms of C. difficile-induced diarrhea are quite variable. Mild diarrhea may be the only finding in the least severe form of disease, whereas patients with severe disease may have high fever, leukocytosis, severe abdominal cramping, marked abdominal tenderness, and profuse diarrhea. Occasionally, symptoms may be so marked as to simulate an acute intraabdominal catastrophe. Diagnosis of C. difficile-induced disease usually is made by detecting C. difficile cytotoxin in the feces of a patient. Assay for cytotoxin in feces of infants is not reliable for diagnosis, however, because of the high incidence of an asymptomatic carrier state in this group. Appropriate therapy includes discontinuation of the offending antimicrobial agent and administration of oral vancomycin when specific antibacterial treatment is indicated.

Eikenella corrodens is a gram-negative rod that has been identified as a cause of endocarditis, osteomyelitis, pneumonia, cellulitis, and other infections. Because it is difficult to grow unless it is incubated in 10% carbon dioxide and because it may be overgrown by other organisms, it can be overlooked as a sinus pathogen. This is a report of the isolation of E corrodens from the sinuses of three patients with sinusitis. Three important features of infection with E corrodens, which are illustrated by these cases, are as follows: (1) the indolence of E corrodens infections; (2) the unusual susceptibility pattern of E corrodens; and (3) the fact that E corrodens is often isolated in mixed culture. The purulent contents of sinus cavities should be cultured in aerobic, anaerobic, and 10% carbon dioxide atmospheres.

MICs of 14 antimicrobial agents for 29 strains of Edwardsiella tarda were determined by an agar dilution method. Of the agents tested, ciprofloxacin, enoxacin, and norfloxacin were the most active on a weight basis. All strains were also susceptible to clinically achievable concentrations of ampicillin, chloramphenicol, tetracycline, trimethoprim, sulfamethoxazole, trimethoprim plus sulfamethoxazole, cefotaxime, and gentamicin. Ninety percent of the strains demonstrated high-level resistance to polymyxin B and colistin.

To evaluate the effects of parenteral cefoxitin therapy on human fecal flora, we cultured fecal specimens obtained from six patients before, during, and after therapy and used standard methods to identify and quantify all microorganisms. The major changes (observed in at least three patients) included the acquisition or proliferation of group D Streptococcus species, coagulase-negative Staphylococcus species, cefoxitin-resistant members of the family Enterobacteriaceae, Pseudomonas species, and various species of the Bacteroides fragilis group. The most striking finding was ingrowth of Clostridium difficile, noted in five of the six patients. There was concomitant eradication or decrease of cefoxitin-susceptible Enterobacteriaceae family members, Bacteroides species other than the B. fragilis group, Clostridium species other than C. difficile, and Lactobacillus species. These marked alterations of fecal flora may have important clinical consequences.

In a double-blind, randomized, controlled trial, 249 patients with complicated urinary tract infections received either 400 mg. enoxacin or 160 mg. trimethoprim plus 800 mg. sulfamethoxazole orally every 12 hours for 14 days. The clinical outcome at the end of treatment revealed that all 89 evaluable patients (100 per cent) in the enoxacin group and 88 of 90 (98 per cent) in the trimethoprim-sulfamethoxazole group had satisfactory clinical responses (cure or improvement). Bacteriological effectiveness was measured cumulatively based on responses during and at the end of treatment, and 7 days later at followup. Satisfactory bacteriological responses (eradication or superinfection at all evaluations throughout the study) were achieved in significantly more (p equals 0.03) patients treated with enoxacin (93 per cent) than in those treated with trimethoprim-sulfamethoxazole (83 per cent). Both study medications were well tolerated. These results indicate that oral enoxacin was more effective clinically and bacteriologically (the latter statistically so) than trimethoprim-sulfamethoxazole when given as empiric therapy in the treatment of complicated urinary tract infections.