Is combined modality therapy necessary for advanced Hodgkin''s disease?

Urinary infections complicated by structural anomalies, metabolic alterations, abnormalities of host response, or unusual or difficult-to-treat pathogens commonly occur in our practices. Therapeutic regimens for most of these patient populations are empiric and unproven. Our understanding of specific microbial virulence factors is inadequate. Until well-designed interventions are proven, management strategies will depend on clinical biases and "trial and error" therapeutic attempts. Presumably, over the course of the next decade, better answers will emerge that will improve our ability to prevent and more adequately manage our patients with complicated UTIs.     

Nosocomial transmission of opportunistic infections

Immunocompromised patients are at high risk for opportunistic infections. Traditionally, these infections were thought to arise from endogenous reactivation of previously acquired latent infections, and nosocomial transmission therefore was deemed to be so unlikely that no special infection control interventions were needed to prevent transmission in healthcare settings. However, new data have challenged this view and suggest that some opportunistic pathogens are transmissible from one immunosuppressed patient to another. Epidemiological investigations, molecular genotyping, animal studies, and air-sampling experiments lend support to the hypothesis that reinfection with opportunistic pathogens does occur, that airborne transmission is possible, and that nosocomial spread is a plausible explanation for case clusters. Taken together, these observations support the view that some opportunistic infections are exogenous in origin and that additional epidemiological investigations are needed to define the true risk of nosocomial spread and need for isolation.     

Microbial toxins

Microbial toxins represent major virulence determinants of pathogenic bacteria. Endotoxins are lipopolysaccharides of the gram-negative bacterial cell wall. They exert their action via deregulating host cell function and stimulating cytokine overproduction. Exotoxins are proteins that can conveniently be grouped into three major categories. The first are intracellularly active molecules, all of which have to date been identified as enzymes. The second are membrane-damaging molecules, most of which create transmembrane pores. The third are the superantigens that cross-link T cells with antigen-presenting cells, thus causing cytokine overproduction. Most pathogens elaborate several toxins that can synergize in their detrimental action. Research on microbial toxins has fundamentally advanced our understanding of the pathogenesis of bacterial infections in the past two decades.     

Entry of pathogens into the central nervous system

The blood-brain barrier (BBB) is formed by the tight junctions of the cerebral capillary endothelium and the choroid plexus epithelium. The molecular anatomy of the tight junction resembles that of a polarized, transporting epithelium, suggesting some model cell culture systems can provide insight into traffic into the central nervous system. Pathogens target both the endothelium, causing encephalitis, and the choroid plexus, leading to meningitis. Routes of entry are diverse including paracellular and transcellular penetration. In addition, circulating microbial products can induce loss of BBB function. Understanding the heterogeneous molecular interactions between pathogens and the BBB may provide avenues to interrupt the devastating neurological sequelae that accompany central nervous system infections.     

Transformation of vibrios with R factors from enterobacteria

The microflora of normal skin in 16 patients with repeated staphylococcal and streptococcal skin infections was examined to determine whether abnormalities existed which would indicate a protective role for the indigenous flora against colonization by pathogens. Five sites-hands, feet, axilla, groin and back-were examined quantitatively and qualitatively and compared with a control group. Total populations of indigenous flora were significantly higher from patients with repeated skin infections of the back, axillae and feet. The frequency of isolation of different species from normal skin was comparable between the control and experimental groups, with the exception of the incidence of Staphylococcus aureus and Proteus species which were isolated only from patients with repeated skin infections. Gram-negative bacteria were isolated with comparable frequency between the two groups, but patients with repeated skin infections tended to carry gram-negative bacteria on multiple sites. It was concluded from the high population of indigenous flora and the types of microogranisms present that the microflora of normal skin did not appear to protect patients with repeated skin infections against colonization by pathogens. The presence of high populations of Staphylococcus aureus on the normal skin of patients with repeated skin infections would appear to be the most important contributing factor.     

Infection prevention and control in the long-term-care facility. SHEA Long-Term-Care Committee and APIC Guidelines Committee

More than 1.5 million residents reside in US nursing homes. In recent years, the acuity of illness of nursing home residents has increased. Long-term-care facility residents have a risk of developing nosocomial infection that is similar to acute-care hospital patients. A great deal of information has been published concerning infections in the long-term-care facility, and infection control programs are nearly universal. This position paper reviews the literature on infections and infection control program in the long-term-care facility, covering such topics as tuberculosis, bloodborne pathogens, epidemics, isolation systems, immunization, and antibiotic-resistant bacteria. Recommendations are developed for long-term-care infection control programs based on interpretation of currently available evidence. The recommendations cover the structure and function of the infection control program, including surveillance, isolation, outbreak control, resident care, and employee health. Infection control resources also are presented.     

Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum

The pathogenic potential of Fusobacterium nucleatum and its significance in the development of periodontal diseases, as well as in infections in other organs, have gained new interest for several reasons. First, this bacterium has the potential to be pathogenic because of its number and frequency in periodontal lesions, its production of tissue irritants, its synergism with other bacteria in mixed infections, and its ability to form aggregates with other suspected pathogens in periodontal disease and thus act as a bridge between early and late colonizers on the tooth surface. Second, of the microbial species that are statistically associated with periodontal disease, F. nucleatum is the most common in clinical infections of other body sites. Third, during the past few years, new techniques have made it possible to obtain more information about F. nucleatum on the genetic level, thereby also gaining better knowledge of the structure and functions of the outer membrane proteins (OMPs). OMPs are of great interest with respect to coaggregation, cell nutrition, and antibiotic susceptibility. This review covers what is known to date about F. nucleatum in general, such as taxonomy and biology, with special emphasis on its pathogenic potential. Its possible relationship to other periodontal bacteria in the development of periodontal diseases and the possible roles played by OMPs are considered.     

Intensive (pasture) beef cattle operations: the perspective of New Zealand

Beef production in New Zealand has characteristics typical of a temperate climate and pasture-based animal husbandry. The specific pathogens which may contaminate fresh beef and which are empirically considered to be of public health importance are similar to those in other countries with temperate climates, i.e. Salmonella, Campylobacter, Escherichia coli O157:H7, Listeria monocytogenes and Toxoplasma gondii. With the exception of T. gondii, it is likely that almost all transmission of these hazards through consumption of beef results from unseen microbial cross-contamination from gastrointestinal sources during slaughter, dressing and further processing. Gaining comprehensive information on carcass contamination levels is an essential first step in establishing food safety objectives for a particular beef production system, and in designing risk-based hazard analysis and critical control point (HACCP) plans. It is likely that the lower mean and maximum numbers of indicator micro-organisms on New Zealand carcasses (when compared with other countries) are in part due to the pre-slaughter cleanliness status of cattle reared under temperate, pasture conditions. Similarly, the failure to detect specific pathogens of gastrointestinal origin in a comprehensive baseline survey most probably reflects the limited pathway for faecal contamination during slaughter and dressing under processing conditions in New Zealand. The New Zealand example provides strong evidence for the need to design HACCP plans according to the specific national (or regional) situation. Reducing all pathways for faecal contamination of products to the maximum extent practicable will be the most important factor in achieving desired food safety objectives for fresh beef. Variable densities of microbial pathogens in gastrointestinal contents are also likely to have a significant effect on subsequent contamination levels of beef carcasses: however, effective controls for limiting the presence of most pathogens of concern in the live animal have yet to be identified.     

Magnitude and prevention of nosocomial infections in the intensive care unit

Nosocomial infections among intensive care unit (ICU) patients usually are related to the use of invasive devices (e.g., mechanical ventilators, urinary catheters, or central venous catheters). This article discusses the impact of these devices and other risk factors for nosocomial infection in ICU patients. Data on etiologic pathogens and device-related infection rates from the National Nosocomial Infection Surveillance System are presented, general infection control guidelines for ICUs are reviewed, and special infection control problems encountered in ICUs are discussed.     

Monoassociation with Lactobacillus acidophilus UFV-H2b20 stimulates the immune defense mechanisms of germfree mice

Probiotics are formulations containing live microorganisms or microbial stimulants that have some beneficial influence on the maintenance of a balanced intestinal microbiota and on the resistance to infections. The search for probiotics to be used in prevention or treatment of enteric infections, as an alternative to antibiotic therapy, has gained significant impulse in the last few years. Several studies have demonstrated the beneficial effects of lactic acid bacteria in controlling infection by intestinal pathogens and in boosting the host's nonspecific immune response. Here, we studied the use of Lactobacillus acidophilus UFV-H2b20, a lactic acid bacterium isolated from a human newborn from Vi?osa, Minas Gerais, Brazil, as a probiotic. A suspension containing 10(8) cells of Lactobacillus acidophilus UFV-H2b20 was inoculated into groups of at least five conventional and germfree Swiss mice to determine its capacity to stimulate the host mononuclear phagocytic activity. We demonstrate that this strain can survive the stressing conditions of the intestinal tract in vivo. Moreover, the monoassociation of germfree mice with this strain for seven days improved the host's macrophage phagocytic capacity, as demonstrated by the clearance of a Gram-negative bacterium inoculated intravenously. Monoassociated mice showed an undetectable number of circulating E. coli, while 0.1% of the original inoculum was still present in germfree animals. Mice treated with viable or heat-killed Lactobacillus acidophilus UFV-H2b20 presented similarly improved clearance capacity when compared with germfree controls. In addition, monoassociated mice had twice the amount of Kupffer cells, which are responsible for the clearance of circulating bacteria, compared to germfree controls. These results suggest that the L. acidophilus strain used here stimulates a nonspecific immune response and is a strong candidate to be used as a probiotic.     

Vascular infections: exceeding the threshold

During fiscal year 1988, our hospital infection control practitioner identified a 400% increase in the incidence of vascular surgery nosocomial infections. The six graft and six amputation infections were validated as nosocomial against hospital definitions adopted from the Centers for Disease Control. Our Infection Control Committee mandated an audit of the infected vascular surgery patients using a case/control design to identify and examine associated variables that may need attention. The significant finding was microbial resistance to prophylactic antibiotics used during surgery (p > 0.0001, Fisher's exact). The use of vancomycin as a prophylactic antimicrobial agent for all major vascular cases was recommended to the surgeons.     

A general framework illustrating an approach to quantitative microbial food safety risk assessment

Hazard analysis critical control point (HACCP), risk assessment, predictive microbiology, and dose-response modeling have been recognized as important tools for the assessment and management of health risks posed by food-borne pathogens. Unfortunately, the biology of both the food chain and food poisoning is complex and dynamic. Therefore, mathematical modeling of microbial risk from food production through to consumption and illness is difficult. Nevertheless, previous authors have made impressive progress in modeling specific pathogen-food-consumer combinations. In this study a framework for a Monte Carlo model of a generic food system was developed. It links together food ingredients, batch processing, cross contamination, microbial growth, cooking, recontamination, consumption, human exposure to pathogens, the dose-response relationship, and the biologic and economic impact components of such risks. This framework is presented to illustrate one potential approach to quantitative risk assessment for microbial food safety. It requires refinement with appropriate distributions and mathematical relationships before it can be applied to a specific pathogen-food-consumer situation.     

Basic and clinical control of nosocomial infections

Nosocomial infections, especially opportunistic infections and occupationally acquired infections, are causing major problems in perioperative period. Opportunistic infections are increased by opportunism secondary to antibiotic therapy and lower body defences. Organisms that cause opportunistic infections come from either exogenous or endogenous sources. Exogenous infections result from transmission of organisms from a source other than the patient. Control of person-to-person spread, such as handwashing and gown technique, disinfection and sterilization of equipment, and environmental cleaning are necessary to prevent exogenous infections. Endogenous infections are caused by the patient's own flora. Antibiotic policies are required to prevent endogenous infections. The main preventive measure of occupationally acquired infections, especially blood-borne infections, is practices of universal precautions. Universal precautions are intended to prevent parenteral, mucous membrane, and nonintact skin exposures to blood-borne pathogens in health care settings.     

Value of CT angiography for postoperative assessment of patients with iliac artery aneurysms who have received endovascular grafts

OBJECTIVE: To determine the pathologic outcome in human immunodeficiency virus (HIV)-seropositive individuals with nonspecific bronchoalveolar lavage (BAL) cytology. STUDY DESIGN: The study group consisted of 126 cytologically negative or nonspecific BAL specimens from HIV-seropositive adults. Concurrent microbial cultures and transbronchial biopsies, as well as subsequent pulmonary cytology, lung biopsy or autopsy results were reviewed. Additionally, the cytologic morphology of specimens from patients found to have a potential bacterial pathogen was reviewed. RESULTS: In the 126 cases with nonspecific BAL cytology, a potential pulmonary pathogen was identified from a concurrent or subsequent pathologic specimen in 27% of cases, while no pathogen was identified in 73% of cases. Bacteria and fungi were the most common pathogens identified. Microbial cultures alone identified the pathogen in 59% of cases, while transbronchial biopsy added information in only 9%. Specimens with marked acute inflammation often yielded bacterial pathogens on microbial culture. CONCLUSION: A potential pulmonary pathogen can be identified in 27% of HIV-seropositive individuals with negative BAL cytology using other diagnostic modalities. Bacterial pathogens are most common and are usually identified by microbial culture. Marked acute inflammation in a BAL specimen is often associated with bacterial pneumonia.     

Secular trends in the etiology of nosocomial infection at a teaching hospital in Taiwan, 1981-1994

Surveillance system of nosocomial infection was established in 1980 at the National Taiwan University Hospital (NTUH). To identify pathogens and the secular trends in the etiology of nosocomial infection from 1981 to 1994, the prospective, hospital-wide nosocomial surveillance data were analysed. During this period, 22,146 pathogens causing nosocomial infections were isolated. Gram-negative aerobic bacteria remained the major pathogens, but gram-positive cocci and fungi increased rapidly in the past 14 years. When the overall pathogen distribution is examined, Pseudomonas areuginosa was the most frequently isolated pathogen, but Candida albicans and other yeasts have taken the leading position since 1993. Staphylococcus aureus and coagulase-negative staphylococci also increase significantly in recent years. When the pathogens causing infection at the 4 major sites were examined. P. aeruginosa was the pathogen most often associated with respiratory tract and surgical wound infections. In blood stream and urinary tract infections, we observed Escherichia coli was replaced by C. albicans and other yeasts as a most common isolate in these years. In addition, C. albicans and other yeasts and methicillin-resistant S. aureus (MRSA) are emerging as major nosocomial pathogens at NTUH. C. albicans and other yeast increased from 1.8% in 1981 to 14.9% in 1994 in the overall nosocomial infection. The increase was found in the blood stream (2.1% to 16.2%) and urinary tract infections (5.4% to 24.7%). Of 1,742 nosocomial S. aureus isolates, the percentage of MRSA rose from 12.5% in 1981 to 55.2% in 1994. The high percentage of MRSA was observed at 4 major anatomic sites of infection. In summary, significant shifts in the pathogens of nosocomial infection have occurred in the past 14 years at NTUH, and the distribution of nosocomial pathogens was similar to those reported in the United States in recent years.     

Fungal plasma membrane proton pumps as promising new antifungal targets

Fungi are widely dispersed in nature and frequently appear as pathogens in the animal and plant kingdoms. The incidence of opportunistic fungal infections in humans has increased due to the human immunodeficiency virus and the application of modern medical approaches that subvert natural protective barriers to infection. Also, fungal blights continue to threaten crops worldwide. As a result, new antifungal agents are needed to address these critical problems. Existing antifungals can be used to effectively treat most cases of topical infection caused by the opportunistic pathogen Candida albicans, which is the principal agent of nosocomially acquired fungal infections. However, life-threatening, disseminated Candida infections are treated with more modest success. Existing antifungals can be toxic or ineffective because of natural resistance or even induced resistance. This limited efficacy largely reflects the restricted range of cellular targets considered during the development of current antifungals. The advancement of highly selective fungicidal reagents requires the recognition of new essential cellular targets. The fungal plasma-membrane proton pump is a high-abundance essential enzyme with a number of well-understood molecular properties that should facilitate the development of new antifungals. The proton pump is important for intracellular pH regulation and the maintenance of electrochemical proton gradients needed for nutrient uptake. It is a member of the P-type class of ion-transport enzymes, which are present in nearly all external cellular membranes. Typical P-type enzymes such as the Na+,K(+)-ATPase and H+,K(+)-ATPase are well established as specific targets for surface-active cardiac glycosides and anti-ulcer therapeutics. The development of new classes of selective antifungals targeted to the proton pump will require exploitation of the well-characterized genetic, kinetic, topological, regulatory, and drug-interaction features of the fungal enzyme that discriminate it from related host P-type enzymes. New antifungal drugs of this type should be relevant to the control of fungal pathogens of medical and agricultural importance and may be applicable to the control of intracellular parasites that also depend on closely related proton pumps for survival.     

Infections caused by multiresistant enterococci in Norway

During the last decade antimicrobial resistant pathogens have become a major medical problem. Internationally, multiresistant enterococci have increased nosocomial morbidity and mortality. Such strains are often resistant to ampicillin, aminoglycosides, and glycopeptides such as vancomycin. The spread of these strains has been shown to correlate to the use of antibiotics and the practice of suboptimal infection control within health care facilities. The current situation in Norwegian hospitals is presented, including the only six cases with infections and the three carriers of vancomycin resistant enterococci found to date. Surveillance in the hospitals shows that such strains are uncommon in non-infected patients. To maintain this favourable situation it is necessary to continue to practice effective methods of infection control and to employ sound antibiotic policies.     

Delivery of epitopes by the Salmonella type III secretion system for vaccine development

Avirulent strains of Salmonella typhimurium are being considered as antigen delivery vectors. During its intracellular stage in the host, S. typhimurium resides within a membrane-bound compartment and is not an efficient inducer of class I-restricted immune responses. Viral epitopes were successfully delivered to the host-cell cytosol by using the type III protein secretion system of S. typhimurium. This resulted in class I-restricted immune responses that protected vaccinated animals against lethal infection. This approach may allow the efficient use of S. typhimurium as an antigen delivery system to control infections by pathogens that require this type of immune response for protection.     

Central nervous system infections in patients with malignant diseases

Infections of the nervous system remain a significant source of morbidity and mortality in patients with cancer. This paper reviews the main pathogens and emphasizes some of the principles of diagnosis and management of nervous system infections in cancer patients. Due to immunosuppression, diagnosis is more difficult in this group, secondary to the multitude of potential pathogens, and often by their atypical presentations. Fever or headache are often the only symptoms. Clinical history and general examination should guide appropriate studies such as neuroimaging. CSF analysis, cultures, and brain biopsy. Diagnostic evaluation should be pursued rapidly and aggressively since specific treatments can often reduce morbidity and mortality. Bacterial infections are generally due to break-down of the natural barriers and neutropenia. In neutropenia, Pseudomonas aeruginosa, and Enterobacteriae are the most frequent etiology. If all causes of immunodepression are included, Listeria monocytogenes meningitis is the main bacterial infection encountered. Fungal infections have emerged as a major cause of death among cancer patients. The prognosis of cryptococcosis and histoplasmosis meningitis are markedly improved with new antifungal therapy. Aspergillosis and Mucormycosis, which may cause cerebral abcesses and secondary vascular complications, are almost always fatal. The incidence of meningo-cerebral Candidiasis is often underestimated. Similar to Histoplasmosis, it is frequently disseminated. Viral infections are mainly seen in patients with T-lymphocyte defects. Herpes-simplex virus and Varicella-Zoster virus encephalitis should quicky lead to intravenous treatment with Acyclovir. As in AIDS patients, cerebral toxoplasmosis is the most frequent parasitic infection and appropriate therapy greatly reduces morbidity. It should be emphasized that multitude pathogens are often seen in cancer patients. Despite development of new therapeutic agents, central nervous system infections should still be considered life-threatening. Therefore, antibacterial, antifungal, and antiviral prophylaxis should be the rule for all cancer patients.     

Enteric pathogens in severe forms of acute gastroenteritis in Ghanaian children

Diarrheal disease is the major cause of childhood morbidity in developing countries. Although malnutrition is known as a risk factor for severe gastroenteritis, the role of enteric pathogens in the clinical severity is unclear. The present study was conducted in well nourished Ghanaian preschool children during a 3 month period of the rainy season to assess the relationship between enteric pathogens and severe gastroenteritis. Two hundred and twenty-five children with acute gastroenteritis and 64 age-matched control children were prospectively examined for the severity of dehydration and enteric pathogens in their stools. Of the 225 children with gastroenteritis, 69.8% (157/225) had mild dehydration and 30.2% (68/225) had severe dehydration. Bacteria were similarly isolated in stool samples from children with mild and severe dehydration and controls. Rotavirus accounted for 20.6% of children with severe dehydration and was more often isolated in stools from patients with severe dehydration than those from controls. Furthermore, the mixed infections associated with rotavirus and bacteria were more often found in patients with severe dehydration than those with mild dehydration or controls. Parasites were similarly found at low incidences among the three groups. The present study implied that rotavirus was more responsible for severe gastroenteritis than bacteria or parasites. However, factors other than enteric pathogens must be sought in a considerable number of severe cases. A large scale study throughout a year is recommended to obtain more precise information that would reflect the seasonal variation of rotavirus infections.