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PubMed2001

Cephalosporins in surgical prophylaxis.

Controlled clinical trials have shown that antimicrobial prophylaxis can lower the incidence of infection after certain operations, thus reducing morbidity, hospital stay, antibiotic usage and mortality due to sepsis. An effective prophylactic regimen should be directed against the most likely infecting organisms, but need not be active against every potential pathogen. Infection can be prevented when effective concentrations are present in the blood and the tissue during and shortly after the procedure. Therefore, antimicrobial prophylaxis should begin just before the operation: beginning earlier is unnecessary and potentially dangerous, beginning later is less effective. A single-dose prophylaxis after the induction of anesthesia is sufficient. If surgery is delayed or prolonged, a second dose is advisable if an antimicrobial drug with a short half-life is used. Postoperative administration is unnecessary and is harmful. Cephalosporins are considered to be the drug of choice, because they offer fewer allergic reactions. From the first generation cephalosporins, cefazolin has been widely recommended with success. From the second generation cephalosporins, cefuroxime, cefamandole and cefoxitin are increasingly recommended. Their antistaphylococcal activity is somewhat less strong but their activity against gram-negative bacteria is stronger. In addition, cefoxitin has good activity against anaerobes. Third generation cephalosporins, such as cefotaxime, cefoperazone, ceftriaxone, ceftazidime or ceftizoxime are generally not recommended for surgical prophylaxis. Despite these recommendations, they have been accepted by the medical community and are today in use in many countries as the most common drugs in surgical prophylaxis. Ceftriaxone in particular, is far exceeding the sales of any other drug for prophylaxis. Contra-indications, limitations, additional or other drugs and practical recommendations for specific procedures are discussed and the results of several prospective randomized studies are presented.

Antibiotic Prophylaxis↗
PubMed1991

Branhamella (Moraxella) catarrhalis: pathogenic significance in respiratory infections.

OBJECTIVES: To assess the pathogenic significance of Branhamella catarrhalis isolates in patients with respiratory infections and to define the clinical characteristics of such patients. DESIGN AND SETTING: Respiratory specimens were assessed in a three-year prospective study performed in a Brisbane metropolitan hospital. Assessment of the pathogenic significance of isolates of B. catarrhalis was based on four predetermined criteria: (i) clinical evidence of respiratory infection based on history, examination and chest x-ray; (ii) isolation of B. catarrhalis as the sole potential pathogen; (iii) absence of antibiotic treatment in the previous two weeks; and (iv) subsequent clinical response to an antibiotic to which the isolate was sensitive. RESULTS: B. catarrhalis was identified in 118 respiratory samples, 92 (78%) being from patients less than 10 years old. Infection with B. catarrhalis was more commonly seen in winter months and was community-acquired in two-thirds of cases. Isolation of this organism was associated with a broad variety of upper and lower respiratory tract syndromes. Isolates were considered to be of pathogenic significance (all four above criteria satisfied) in 35% of cases and of possible significance (the first and fourth criteria satisfied) in a further 15% of cases. Isolates were more likely to be of pathogenic significance in older patients and in those with pre-existing cardiorespiratory disease; however, a number of serious infections were observed in previously-well children. Expectorated sputum and tracheal aspirates were more likely to yield a clinically significant isolate than nasopharyngeal aspirates. Production of beta-lactamase was demonstrated in 88% of isolates. CONCLUSION: B. catarrhalis causes respiratory infection more frequently than is generally appreciated. Isolation of this organism from the respiratory tract had pathogenic significance or possible pathogenic significance in 50% of our patients. If therapy is indicated in patients with respiratory infection caused by this organism, traditional beta-lactam regimens cannot be relied upon, as shown by the high rate of beta-lactamase production in this study; a tetracycline, erythromycin, a second or third generation cephalosporin, or the combination of a penicillin derivative and beta-lactamase inhibitor should be considered.

Adolescent↗
PubMed2000

Pathogenic role of anti-endothelial cell antibodies in systemic vasculitis.

Antiendothelial cell antibodies (AECA), a heterogeneous group of antibodies quite distinct from the ANCA family, have been detected in variety of diseases which share a varying degree of vessel wall damage. This review is mainly focused on Wegener's granulomatosis, Takayasu's arteritis and Kawasaki syndrome, which provide the best examples to evaluate the pathogenic and prognostic value of AECA. There is increasing evidence to show that AECA might be pathogenic in inducing autoimmune vascular disease. It is relevant to note that the presence and titre of AECA has been correlated with disease activity in systemic vasculitis. Experimental in vitro and in vivo models support a potential pathogenic role for AECA in sustaining immune-mediated vessel inflammation. Rather than being cytotoxic to endothelial cells, AECA are able to up-regulate the expression of adhesion molecules (E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and to induce the secretion of cytokine and chemokine which, in turn, cause leukocyte recruitment and adhesion. A recent idiotypic animal model has provided further evidence that AECA can be pathogenic.

Autoantibodies↗
PubMed1990

Serious infections caused by coagulase-negative staphylococci in intravenous drug users.

While Staphylococcus aureus has been a well-recognized pathogen in patients who use illicit intravenous drugs, coagulase-negative staphylococci are not generally appreciated as causes of infectious complications in intravenous drug users. The authors present data suggesting the coagulase-negative staphylococci are potential pathogens in these high risk patients.

Adult↗
PubMed1996

Microbiology and management of sinusitis.

PURPOSE: The pathophysiology, microbiology, and treatment of acute and chronic sinusitis are reviewed. MATERIALS AND METHODS: The current literature is reviewed. REVIEW: Sinusitis generally develops as a complication of viral or allergic inflammation of the upper respiratory tract. Bacterial pathogens contribute to the inflammatory process-Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are predominant in acute sinusitis, while anaerobic bacteria and Staphylococcus aureus are predominant in chronic sinusitis. Pseudomonas aeruginosa has emerged as a potential pathogen in the immunocompromised patients and in those who have nasal tubes or catheters. Many of these organisms recovered from sinusitis became resistant to penicillins either through the production of beta-lactamase (H. influenzae, M. catarrhalis, S. aureus, Fusobacterium sp., and Prevotella sp.) or through changes in the penicillin-binding protein (S. pneumoniae). The pathogenicity of beta-lactamase-producing bacteria is expressed directly through their ability to cause infections, and indirectly through the production of beta-lactamase. CONCLUSIONS: The indirect pathogenicity is conveyed not only by surviving penicillin therapy, but also by "shielding" penicillin-susceptible pathogens from the drug. The direct and indirect virulent characteristics of these bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections. Proper therapy, with antimicrobial and decongestants combined when indicated with surgical drainage and correction of pathology, constitutes the cornerstone of management of sinusitis.

Acute Disease↗
PubMed1994

Vaccine potential of a herpes simplex virus type 1 mutant with an essential glycoprotein deleted.

Several approaches to the production of vaccines to human herpesviruses have been proposed. Subunit vaccines, subunits delivered by live vectors, and rationally attenuated vaccines have all been shown to be efficacious in animal models but suffer from uncertainties as to the roles of individual genes involved in pathogenesis and the most relevant components of the immune response required for protection in humans and the target antigens involved. With these problems in mind, we examined the vaccine potential of a fully disabled herpes simplex virus type 1 mutant that is capable of only a single round of replication, since a virus of this type should induce the full spectrum of immune responses but has no pathogenic potential. A virus has been described which lacks essential glycoprotein H (gH) and can be propagated in a cell line which supplies gH in trans (A. Forrester, H. Farrell, G. Wilkinson, J. Kaye, N. Davis-Poynter, and T. Minson, J. Virol. 66:341-348, 1992). Infection of normal cells with this mutant is indistinguishable from a wild-type infection, except that the resulting progeny are gH negative and noninfectious: the virus is self-limiting. Infection of mice by the ear pinna route was similarly self-limiting in that input infectivity decreased rapidly at the inoculation site and no infectivity was detected in sensory ganglia. Animals given a wide range of doses of the gH-negative mutant produced both humoral and T-cell responses to herpes simplex virus type 1 and proved solidly resistant to challenge with a high dose of wild-type virus. The gH-negative mutant is presumably capable of establishing a latent infection, but since no infectious virus was detected in numerous attempts to reactivate the mutant, the risk of a pathogenic outcome is minimal.

Animals↗
PubMed1995

Contact lens wear by hospital health care staff: is there cause for concern?

Microbial keratitis can occur in association with contact lens wear. The absolute risk of infection is low but may be enhanced as a consequence of increased exposure to potentially pathogenic microbes in a hospital setting. There is variation in risk depending on type of lens worn and its modality of use. Extended-wear lenses carry the greatest risk. Pseudomonas aeruginosa and Acanthamoeba are causes of potentially devastating ocular infections in contact lens wearers. The risk of these infections could be reduced by fastidious hygiene practice. Hydrogen peroxide disinfection is recommended when a storage case is included in the care regimen. This should be cleaned thoroughly and dried prior to disinfection and never exposed to tap water. Daily wear of one-day 'disposable' soft contact lenses or use of rigid gas permeable lenses is recommended for hospital staff. Contact lenses should be removed immediately and discarded or disinfected if the eye becomes contaminated and/or use of an eyewash is required.

Contact Lenses↗
PubMed2005

Regulation of intestinal epithelial function: a link between opportunities for macromolecular drug delivery and inflammatory bowel disease.

The intestinal epithelium performs a multitude of tasks related to digestion and homeostasis. As a consequence of ingestion, this tissue must also participate in activities associated with protecting the body from potential pathogenic agents and toxic materials. To efficiently perform tasks associated with digestion and these protective functions, the intestinal epithelium has established several anatomical, biochemical and physiological barriers to impede unregulated uptake of materials. In order to perform functions of digestion and homeostasis, the intestinal epithelium uses mechanisms that allow dynamic modulation of regulated uptake pathways that can respond rapidly to changes in diet, health and challenges from pathogenic agents and macromolecules. This review focuses on specific, recent advances made in understanding cellular pathways and mechanisms that regulate dynamic processes of these barriers and examines the feasibility of drug delivery strategies focusing on macromolecular therapeutics potentially useful in the treatment of inflammatory bowel disease (IBD).

Animals↗
PubMed2005

Achievement by proxy distortion in sports: a distorted mentoring of high-achieving youth. Historical perspectives and clinical intervention with children, adolescents, and their families.

This article describes potentially pathogenic behavior in youth sports. It delineates the four stages of achievement by proxy distortion (ABPD) behavior and attempts to raise awareness of that behavior and to facilitate communication among sports medicine and psychiatry professionals of the potential for exploitation and abuse of children and adolescents by parents, mentors, coaches, and the systems that nurture and develop these children. Information is presented to distinguish motivations behind normal parenting from those that lead to risky sacrifice, objectification of the child, and potential abuse. Distinct abuse stages of ABPD are described. The authors identify "red flags" that indicate distorted views and potentially harmful behavior toward children.

Achievement↗
PubMed2003

Anti-microbial activities of mannose-binding lectin.

Mannose-binding lectin (MBL; also known as mannan-binding lectin) is involved in first-line defence by binding to bacteria, viruses, protozoa and helminths through a pattern-recognition mode of detection and then initiating a range of host responses. Currently, we have been unable to extrapolate from what we know of the biochemistry of MBL binding to predict accurately the interaction of MBL with individual micro-organisms; even subtle surface alterations have been shown to have an extensive impact on MBL-mediated recognition of pathogens. MBL has a major protective effect through activation of the complement system via MBL-associated serine proteases (MASPs). This can cause the lysis of Gram-negative bacteria and also opsonize a wide spectrum of potential pathogens for phagocytosis. MBL may also influence phagocytosis in the absence of complement activation through an interaction with one or more collectin receptors. This may also be the basis for a direct effect of the protein on inflammatory responses. MBL can alter the function of microbial structures, such as gp120 of HIV, to prevent infection. The protein may also interact with the components of other cascade systems such as the clotting system, which will have a role in microbial pathogenesis. An understanding of these basic mechanisms will be vital if we are to use purified or recombinant MBL in therapeutic applications.

Bacterial Capsules↗
PubMed2003

Experimental murine hyalohyphomycosis with soil-derived isolates of Fusarium solani.

Two strains of soil-borne Fusarium solani, both characterized for their ability to produce cyclosporin A and C, were examined for their pathogenicity in severe combined immunodeficiency (SCID) and BALB/c male mice. Intravenous (i.v.) infections with F. solani conidia were performed. No mortality was observed after infection with 0.3-1.6 x 10(7) cfu per mouse in SCID and BALB/c mice. When mice were infected with 0.8-1.5 x 10(6) cfu per mouse and 2 days later with 1.2-1.9 x 10(6) cfu per mouse, 28.6-85.7% survival occurred over a 25-day period, depending on the F. solani strain and the inbred mouse line used. Death was preceded by renal insufficiency affecting both kidneys. Furthermore, i.v. injection with heat-killed conidia followed 2 days later by injecting viable conidia resulted in renal infection in both breeds of mice. F. solani isolated from infected organs was more virulent than the original isolate, and 3/8 (37.5%) of BALB/c and 4/7 (57.1%) of SCID mice died after receiving a single dose. Dissemination to the brain was found only in SCID mice, but torticollis was observed in both mouse breeds. Soil-borne F. solani isolates possess poor pathogenic potential for mice, but either two successive infective doses or a primary injection with heat-killed conidia followed by a single infective dose breaks through host defenses in normal and immunoincompetent mice. Mouse passage increased the pathogenicity of two soil-derived F. solani strains.

Animals↗
PubMed1997

Can surgery be justified for patients with periodontitis?

There is a debate concerning the role that surgical procedures should play in the treatment of inflammatory periodontal diseases. This review details some of the situations in which surgery can be of benefit. Benefits include obtaining shallower probing depths and therefore reducing the areas that are hospitable to pathogenic bacteria associated with disease. Also, removal of tooth-accumulated materials such as plaque and calculus in probing depths greater than 5 mm is more predictable with surgery. In some forms of aggressive periodontitis, elimination of potentially pathogenic bacteria is found more frequently with surgical procedures. Regeneration of lost bone and attachment apparatus are predictable only with surgery.

Gingivectomy↗
PubMed2004

An integrated view of suppressor T cell subsets in immunoregulation.

The immune system evolved to protect organisms from a virtually infinite variety of disease-causing agents but to avoid harmful responses to self. Because immune protective mechanisms include the elaboration of potent inflammatory molecules, antibodies, and killer cell activation--which together can not only destroy invading microorganisms, pathogenic autoreactive cells, and tumors, but also mortally injure normal cells--the immune system is inherently a "double-edged sword" and must be tightly regulated. Immune response regulation includes homeostatic mechanisms intrinsic to the activation and differentiation of antigen-triggered immunocompetent cells and extrinsic mechanisms mediated by suppressor cells. This review series will focus on recent advances indicating that distinct subsets of regulatory CD4+ and CD8+ T cells as well as NK T cells control the outgrowth of potentially pathogenic antigen-reactive T cells and will highlight the evidence that these suppressor T cells may play potentially important clinical roles in preventing and treating immune-mediated disease. Here we provide a historical overview of suppressor cells and the experimental basis for the existence of functionally and phenotypically distinct suppressor subsets. Finally, we will speculate on how the distinct suppressor cell subsets may function in concert to regulate immune responses.

Animals↗
PubMed1997

A thermal burn to a prolapsed uterus.

Burns to the concealed area of the perineum, are relatively rare and usually associated with massive burns and a high mortality rate. A rare case of a thermal burn to a prolapsed uterus is described. The victim was a 72-year-old Bedouin woman, with a 70 per cent total body surface area deep burn from an open fire. In addition to the conventional treatment dictated by such a burn, two unique problems must be considered: (1) the common pathogens of the uterus, Neisseria gonorrhoeae, Chlamydia trachomatis and mycoplasma, are different from those of the skin; (2) the lymphatics of the uterus drain directly into the abdominal cavity and the risk of peritonitis and generalized infection is potentially higher. Intravenous, prophylactic, broad-spectrum antibiotics were therefore initiated immediately following admission. These included: cefoxitin, gentamicin and metronidazole a combination that covers both the potential pathogens of the uterus and the common pathogens of the skin. In addition, and for the same reason, Betadine substituted Flamazine for the local treatment of the exposed uterus. Our patient did not survive the burn, but in a similar, unusual case, the local and systematic remedies must protect against uterine pathogens that are not commonly seen in a burn victim.

Aged↗
PubMed1998

Anti-DNA and antiphospholipid antibodies in IVIG preparations: in vivo study in naive mice.

Intravenous immunoglobulins (IVIG) are therapeutic preparations of pooled normal polyspecific immunoglobulin G. We investigated the presence and the in vivo pathogenic potential of autoantibodies against phospholipids and DNA in several commercial IVIG preparations. The presence of autoantibodies and their antiidiotypic antibodies in the IVIG preparations was detected by ELISA. Naive mice were actively immunized with either IVIG preparations or pathogenic monoclonal antibodies (mAbs) against cardiolipin (CL) or DNA, in an attempt to induce autoimmune conditions. The mice were tested for the presence of mouse autoantibodies (auto-Abs) and for clinical parameters of autoimmune diseases. We found high levels of auto-Abs against a panel of phospholipids and DNA, as well as their antiidiotypic Abs, in all the IVIGs. Affinity studies pointed to a lower affinity of auto-Abs of IVIG origin to their respective antigens compared to pathogenic mAbs. Mice immunized with pathogenic anti-CL mAb had high levels of antiphospholipid auto-Abs, accompanied by thrombocytopenia, prolonged aPTT, and an increased fetal resorption rate. Mice immunized with pathogenic anti-DNA mAb had elevated anti-DNA and anti-CL auto-Abs, along with a high erythrocyte sedimentation rate, leukopenia, and significant proteinuria. Following immunization with IgGs from IVIG batches, mice developed high levels of auto-Abs against phospholipids and DNA, similar to mice immunized with pathogenic anti-DNA or anti-CL mAbs, but none of the mice expressed the clinical manifestations compatible with the presence of these autoantibodies. We conclude that commercial IVIG preparations contain high levels of antiphospholipid and anti-DNA auto-Abs, as well as their antiidiotypic Abs. Although these Abs induced the generation of mouse auto-Abs upon active immunization, following idiotypic manipulation they did not prove to be pathogenic in vivo.

Animals↗
PubMed2026

The Effect of Pancreatic Exocrine Insufficiency and Pancreatic Enzyme Replacement Therapy on Gut Microbiome Composition in Pancreatic Disease: A Prospective Cohort Study.

OBJECTIVES: Increasing evidence demonstrates that pancreatic exocrine insufficiency (PEI) is associated with harmful changes to the gut microbiome. The mainstay of PEI treatment is with pancreatic enzyme replacement therapy (PERT), which has been shown to lead to significant survival benefit in pancreatic disease. The aim of this study was to determine how treatment of PEI with PERT affects gut microbiome composition. METHODS: This is a prospective observational cohort study of patients being treated for pancreatic disease at a single centre. PEI status of patients was assessed at the time of recruitment using published diagnostic criteria. Pre-PERT samples were taken before treatment was started and post-PERT samples were taken after at least 4 weeks of treatment. To profile the gut microbiome composition, shotgun metagenomic sequencing was performed with DNA extracted from stool samples. RESULTS: 25 patients with pancreatic disease were included. The abundance of pathogenic bacteria, such as Viridans group Streptococcus and Campylobacter species, was significantly increased in the gut microbiome of patients with PEI compared to those without PEI. Following PERT treatment, analysis of the gut microbiome of treated patients showed a significant reduction in the abundance of multiple pathogenic species, such as those from Viridans group Streptococci, compared to untreated PEI patients. CONCLUSIONS: Treatment with PERT leads to significant changes in the gut microbiome composition of patients with pancreatic disease. Changes include a significant reduction in potentially pathogenic bacteria and so may contribute to the survival benefits seen with PERT treatment in pancreatic disease.

gut microbiome↗
PubMed2006

Phenotypic and molecular characteristics of Escherichia coli isolated from aquatic environment of Bangladesh.

Pathogenic Escherichia coli remains important etiological agent of infantile diarrhea in Bangladesh. Previous studies have focused mostly on clinical strains, but very little is known about their presence in aquatic environments. The present study was designed to characterize potentially pathogenic E. coli isolated between November 2001 and December 2003 from aquatic environments of 13 districts of Bangladesh. Serotyping of 96 randomly selected strains revealed O161 to be the predominant serotype (19%), followed by O55 and O44 (12% each), and 11% untypable. Serotype-based pathotyping of the E. coli strains revealed 47%, 30%, and 6% to belong to EPEC, ETEC, and EHEC pathotypes, respectively. The majority of the 160 strains tested were resistant to commonly used antimicrobial agents. Plasmid pro-filing showed a total of 17 different bands ranging from 1.3 to 40 kb. However, 35% of the strains did not contain any detectable plasmid, implying no correlation between plasmid and drug resistance. Although virulence gene profiling revealed 97 (61%) of the strains to harbor the gene encoding heat-stable enterotoxin (ST), 2 for the gene encoding Shiga toxin (Stx), and none for the gene for heat-labile enterotoxin (LT), serotype-based pathotyping of E. coli was not fully supported by this gene profiling. A dendrogram derived from the PFGE patterns of 22 strains of three predominant serogroups indicated two major clusters, one containing mainly serogroup O55 and the other O8. Three strains of identical PFGE profiles belonging to serogroup O55 were isolated from three distinct areas, which may be of epidemiological significance. Finally, it may be concluded that serotype-based pathotyping may be useful for E. coli strains of clinical origin; however, it is not precise enough for reliably identifying environmental strains as diarrheagenic.

Bangladesh↗
PubMed2001

Identification of virulence attributes of gastrointestinal Escherichia coli isolates of veterinary significance.

The pathogenic strains of Escherichia coli recovered from the intestinal tract of animals fall into categories called enterotoxigenic, enteropathogenic, enterohemorrhagic and necrotoxigenic. The other two categories, enteroinvasive and enteroaggregative, have not been reported in animals. The pathogenicity of these strains is determined by the presence of certain genes that encode adhesins and toxins, are generally organized in large blocks in chromosomes, large plasmids or phages, and are often transmitted horizontally between strains. In this review, we summarize current knowledge of the virulence attributes that determine the pathogenic potential of E. coli strains and the methods available to assess the virulence of the strains. We also discuss the clinical symptoms, the gross and histological lesions, and the molecular diagnostic methods our laboratories have implemented for detecting pathogenic strains of E. coli that are isolated from the gastrointestinal tract of animals.

Adhesins, Escherichia coli↗