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PubMed2000

Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel.

OBJECTIVE: To update recommendations for antiretroviral therapy for adult human immunodeficiency virus type 1 (HIV-1) infection, based on new information and drugs that are available. PARTICIPANTS: A 17-member international physician panel with antiretroviral research and HIV patient care experience initially convened by the International AIDS Society-USA in December 1995. EVIDENCE: Available clinical and basic science data including phase 3 controlled trials; data on clinical, virologic, and immunologic end points; research conference reports; HIV pathogenesis data; and panel expert opinion. Recommendations were limited to therapies available (US Food and Drug Administration approved) in 1999. CONSENSUS PROCESS: The panel assesses new research reports and interim results and regularly meets to consider how the new data affect therapy recommendations. Recommendations are updated via full-panel consensus. Guidelines are presented as recommendations if the supporting evidence warrants routine use in the particular situation and as considerations if data are preliminary or incomplete but suggestive. CONCLUSIONS: The availability of new antiretroviral drugs has expanded treatment choices. The importance of adherence, emerging long-term complications of therapy, recognition and management of antiretroviral failure, and new monitoring tools are addressed. Optimal care requires individualized management and ongoing attention to relevant scientific and clinical information in the field.

Adult↗
PubMed1992

Associations between microbial species in dental root canal infections.

The existence of commensal or antagonistic relationships between microorganisms in the root canals of teeth with apical periodontitis was investigated. Samples were taken from 65 infected human root canals and were analysed according to species, frequency of occurrence and proportion of the total isolated flora. The most frequent species were Fusobacterium nucleatum, Prevotella intermedia, Peptostreptococcus micros, Peptostreptococcus anaerobius, Eubacterium alactolyticum, Eubacterium lentum and Wolinella recta. An odds ratio system was used to calculate positive or negative associations between the isolated bacteria. Strong positive associations were found between F. nucleatum and P. micros, Porphyromonas endodontalis, Selenomonas sputigena and W. recta. There was also a positive association between P. intermedia and P. micros, P. anaerobius and the eubacteria. In general, species of streptococci, Propionibacterium propionica, Capnocytophaga ochracea and Veillonella parvula showed no or negative associations with the other bacteria. The results are consistent with the concept of a special and selective environment occurring in the root canal that is due, in part, to the cooperative as well as antagonistic nature of the relationships between bacteria in the root canal.

Actinomyces↗
PubMed2000

Pneumonia in the immunocompromised host: the role of bronchoscopy and newer diagnostic techniques.

The microbiology laboratory plays an essential role in the laboratory diagnosis of pneumonia in the immunocompromised host. Both the diversity of underlying or predisposing host conditions that increase risk for pneumonia and the variety of microbial agents that may be etiologically responsible make the laboratory's role in the diagnostic process a challenging one. In addition, the laboratory has a number of diagnostic tools available for detection of etiologic agents including conventional stains and cultures as well as newer tests relying on antigen detection and molecular techniques. Respiratory specimens available for testing are also diverse and are often obtained by the use of fiberoptic bronchoscopy, but may be complemented by use of blood samples when dissemination is likely or more recently by urinary antigen testing in select cases. Given the large number of variables in the design of a diagnostic approach to pneumonia in the immunocompromised host, it is critical that laboratorians and clinicians cooperate in the development of protocols that are cost effective and appropriate to their specific clinical settings.

AIDS-Related Opportunistic Infections↗
PubMed2000

The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors.

Toll-like receptors (TLRs) have been shown to participate in the recognition of pathogens by the innate immune system, but it is not clear how a restricted family of receptors has the capacity to recognize the wide spectrum of TLR stimuli known to exist. We report here that two members of the TLR family, TLR2 and TLR6, together coordinate macrophage activation by Gram-positive bacteria and the yeast cell-wall particle, zymosan. TLR6 and TLR2 both are recruited to the macrophage phagosome, where they recognize peptidoglycan, a Gram-positive pathogen component. By contrast, TLR2 recognizes another component, bacterial lipopeptide, without TLR6. The requirement for TLR cooperation is supported by the finding that TLR2 needs a partner to activate tumor necrosis factor-alpha production in macrophages. Dimerization of the cytoplasmic domain of TLR2 does not induce tumor necrosis factor-alpha production in macrophages, whereas similar dimerization of the TLR4 cytoplasmic domain does. We show that the cytoplasmic domain of TLR2 can form functional pairs with TLR6 or TLR1, and this interaction leads to cytokine induction. Thus, the cytoplasmic tails of TLRs are not functionally equivalent, with certain TLRs requiring assembly into heteromeric complexes, whereas others are active as homomeric complexes. Finally, we show that TLR6, TLR2, and TLR1 are recruited to macrophage phagosomes that contain IgG-coated erythrocytes that do not display microbial components. The data suggest that TLRs sample the contents of the phagosome independent of the nature of the contents, and can establish a combinatorial repertoire to discriminate among the large number of pathogen-associated molecular patterns found in nature.

Animals↗
PubMedDate not supplied

Towards the rational use of antibiotics: results of the first International Symposium on the Risk Analysis of Antibiotic Resistance.

The results of four expert working groups on the risk analysis process on anti-microbial resistance are described. They focus on the procedure recommended by the FAO/WHO CODEX Alimentarius Commission in 1999 including hazard identification, hazard characterization, exposure assessment and risk characterization. In all four areas, the current scientific knowledge was evaluated and recommendations for risk management options were given. They will form the basis for mitigating the health risk caused by resistant micro-organisms.

Animals↗
PubMed1987

Isolated brain microvessels as in vitro equivalents of the blood-brain barrier: selective removal by collagenase of the A-system of neutral amino acid transport.

On treatment with collagenase, brain microvessels, together with several protein components, lose some enzymatic activities such as alkaline phosphatase and gamma-glutamyltranspeptidase, whereas no change occurs in the activities of 5'-nucleotidase and glutamine synthetase. The energy-requiring "A-system" of polar neutral amino acid transport is also severely inactivated, whereas the L-system for the facilitated exchange of branched chain and aromatic amino acids is preserved. In the collagenase-digested microvessels, this leads to loss of the transtimulation effect of glutamine on the transport of large neutral amino acids, because such transtimulation is due to a cooperation between the A- and L-systems. By contrast, NH4+ maintains (and even enhances) its ability to stimulate the L-system of amino acid transport, presumably through glutamine synthesis within the endothelial cells.

5'-Nucleotidase↗
PubMed1995

Potential application of human interferon-alpha in microbial infections of the oral cavity.

We have been evaluating the potential use of interferon-alpha (IFN-alpha) against fungal infections of the oral cavity. IFN-alpha has been reported to enhance the antifungal activity of neutrophils. This cytokine is also known to synergize with interleukin-1 in enhancing a number of immunomodulatory responses. To study cytokine involvement in oral defense mechanisms against microbial infection, we first demonstrated the presence of antimicrobial interleukins (IL)-1 alpha, IL-1 beta, and IL-8 in the saliva, which can all augment the microbicidal activity of neutrophils, and the presence of epithelial cells and neutrophils in oral lavage fluid from healthy volunteers. Immunostaining for cytokines produced by these cells showed that the candidate producers of both IL-1 alpha and IL-8 are epithelial cells, but those of IL-1 beta remained inconclusive. We next found that IFN-alpha enhanced IL-1 alpha-augmented neutrophil-mediated anticandidal action while marginally enhancing IL-8- and IL-1 beta-mediated reactions. These results suggest that IFN-alpha is a potential agent for treating oral mycosis by cooperating with endogenous cytokine(s) in the saliva, in addition to its intrinsic antiviral action.

Adult↗
PubMed1982

The cooperation of cefotaxime and desacetyl-cefotaxime with respect to antibacterial activity and beta-lactamase stability.

Desacetyl-cefotaxime, the main metabolite of cefotaxime, possesses a broad antibacterial spectrum. Its activity is lower than that of cefotaxime, but significantly surpasses that of cefazolin against gram-negative bacteria. The beta-lactamase stability of desacetyl-cefotaxime is higher than that of the parent compound. This beta-lactamase stability might be responsible for the synergistic effects of cefotaxime and desacetyl-cefotaxime occasionally seen in in vitro combination studies.

Bacteria↗
PubMed1998

Mechanisms of isoniazid resistance in Mycobacterium tuberculosis: enzymatic characterization of enoyl reductase mutants identified in isoniazid-resistant clinical isolates.

Mutants in the structural gene of the inhA-encoded NADH-dependent 2-trans enoyl-acyl carrier protein reductase were identified from isoniazid-resistant clinical isolates of Mycobacterium tuberculosis. Recombinant InhA proteins with defined single amino acid replacements were expressed in Escherichia coli and purified to homogeneity. Steady-state kinetic parameters for wild type (WT) and I16T, I21V, I47T, and I95P mutants of the enoyl reductase were measured spectrophotometrically. NADH binding to WT and I16T, I21V, I47T, S94A, and I95P mutant reductases were determined by fluorescence spectroscopy and demonstrated that all mutant enzymes had reduced NADH affinity and that NADH binding to all mutants was cooperative as compared with the hyperbolic binding of NADH to the WT enzyme. Since KatG-produced electrophilic derivatives of isoniazid have been suggested to inactivate the enoyl reductase-NADH complex, the kinetics of inactivation for the WT and I21V and I95P mutants was determined. Both mutations resulted in significantly increased values for the apparent first-order rate constant of inactivation.

Antitubercular Agents↗
PubMed1999

New intervention strategies for reducing antibiotic resistance.

Rising antibiotic resistance rates among bacterial pathogens have resulted in increased morbidity and mortality from nosocomial infections. Widespread use of certain antibiotics, particularly third-generation cephalosporins, has been shown to foster development of generalized beta-lactam resistance in previously susceptible bacterial populations. Reduction in the use of these agents (as well as imipenem and vancomycin) and concomitant increases in the use of extended-spectrum penicillins and combination therapy with aminoglycosides have been shown to restore bacterial susceptibility. Studies have shown that education-based methods, as opposed to coercive measures, are effective in changing the prescribing habits of physicians. Cooperative interaction among infectious-disease physicians, clinical pharmacists, microbiology-laboratory personnel, and infection-control specialists is essential to provide useful suggestions regarding antibiotic choice and dosing to the prescribing physician in real time. Several hospitals have implemented antimicrobial resistance management programs based on these findings. The results of these programs validate the use of a multidisciplinary, education-based, antibiotic-resistance management approach.

Anti-Bacterial Agents↗
PubMed1996

Differential Metabolism of Dimethylsulfoniopropionate and Acrylate in Saline and Brackish Intertidal Sediments

In anoxic Spartina alterniflora-dominated sediments along a naturally occuring salinity gradient (the Cooper River estuary, South Carolina, U.S.A.), dimethylsulfoniopropionate (DMSP) was metabolized to dimethyl sulfide (DMS) and acrylate by sediment microbes. The rate of DMSP degradation and acrylate mineralization by sediment microbes was similar at all sites along this 25-km transect. However, sediments amended with acrylate (or DMSP) showed significantly higher rates of N2 fixation (measured as acetylene reduction activity) (ARA) in the saline sediments downstream than brackish sediments. These results are consistent with the fact that acrylate stimulated the rates of both denitrification and CO2 production in the saline sediments at the mouth of the river more than tenfold over rates in brackish sediments. Enrichment experiments indicate that microbes capable of using DMSP or acrylate were not present in upstream sediments despite the fact that microbial biomass, percent organic matter, and both glucose-stimulated ARA and denitrification were highest upstream. It appears that acrylate utilizing, N2 fixing, and denitrifying populations are insignificant in the lower salinity sediments of the estuary. These results may reflect the availability of DMSP, which averaged 10.3 nmol g wet wt-1 of saline sediments and levels less than our detection limit (1 &mgr;M) in brackish sediments.

Journal Article↗
PubMed1992

Adhesion of mutants streptococci to glass with and without a salivary coating as studied in a parallel-plate flow chamber.

Deposition and adhesion to glass with and without a salivary coating in a parallel-plate flow chamber were studied with four strains of mutans streptococci. Stationary-state adhesion of the strains to uncoated glass ranged from 0.3 x 10(6) cm-2 (Streptococcus rattus HG218) to 12.7 x 10(6) cm-2 (Streptococcus sobrinus HG1025) and generally decreased after saliva coating of the glass. The poor adhesion found for S. rattus HG218 to both uncoated and saliva-coated glass could be due to its relatively high negative surface-charge. Deposition efficiencies of all strains were greater than or equal to 1 for uncoated glass and decreased greatly after saliva coating of the glass. Possibly, adhesion to a saliva coating is less efficient and more time-consuming than that to uncoated glass, because stereochemical groups in the pellicle and on the cell surfaces may have to re-arrange before an effective interaction can occur. Desorption rates, measured 1000 s and 5000 s after the start of an experiment, decreased by a factor of ten upon a five-fold increase in contact time, indicative of a two-phase adhesion process. Of the four strains studied, only Streptococcus cricetus HG737 showed a minor positive cooperativity on saliva-coated glass, possibly mediated by surface appendages observed by transmission electron microscopy on negatively-stained cells. Retention of adhering bacteria was strain-dependent on uncoated glass, but was identical for all strains on saliva-coated glass, which suggests that the structure and composition of the pellicle may be more important with respect to the retention of adhering cells than the cell-surface properties themselves.

Bacterial Adhesion↗
PubMed2005

TLR-dependent IL-4 production by invariant Valpha14+Jalpha18+ NKT cells to initiate contact sensitivity in vivo.

LPS stimulated B-1 cell polyclonal in vivo IgM responses depend on IL-4 release by invariant Valpha14+Jalpha18+ NKT (iNKT) cells. The IgM Abs can recruit effector T cells to mediate contact sensitivity. LPS activates the B-1 cell response just 1 day later, and depends on CD1d, iNKT cells, IL-4, TLR4, and MyD88. LPS in vivo and in vitro stimulates rapid preferential production of IL-4 in hepatic iNKT cells within 2 h. TLR4 were demonstrated in iNKT cells by flow cytometry and functional studies. Thus, innate microbial stimulation via TLR can activate iNKT cell and B-1 cell collaboration. The result is polyclonal IgM Ab responses capable of recruiting Ag-specific T cells into tissues. This may be involved in the promotion of autoimmunity by infectious agents.

Animals↗
PubMedDate not supplied

[Failures of standardized treatments in pulmonary tuberculosis. Possibilities of prevention and therapeutic recovery].

In view of a better knowledge of therapeutic failures in operational conditions four groups of patients were analyzed, which included a total of 1511 patients, both new cases and patients re-admitted for tuberculosis of the pulmonary apparatus, that had been treated according to standardized regimens. In three of these groups failures had been recorded at a rate of 3,9% intra-therapeutic failures and 7,6% post-therapeutic ones in the first 18 months after completing the therapy. Out of the four groups a lot was selected, which included 127 cases of therapy failure. This lot was studied under the aspect of causes of the failure and of the possibilities for recovery. The major causes of the failure were non-cooperation of patients (in 48% of the cases), the initial severity of the lesions, associated diseases, the re-admittance, the secondary resistance. Recovery of the intra-therapeutic failures was possible in 46% of the cases, and of patients with post-therapeutic failure in 72% of the cases. On the basis of an analysis of risk factors a series of proposals are made for preventing such failures.

Adolescent↗
PubMed1984

[Cooperative study on the recurrence of lung tuberculosis in East Germany].

144 patients with bacteriologically positive results were analysed out of 258 relapses of pulmonary tuberculosis within one year (1979/80) to find the causes which are favouring relapses. It has been found that in 28% an inadequate chemotherapy, in 16% uncontrolled use of drugs, and in 13% of cases uncooperative attitude of patients were supposed causes of relapse. Causes of relapse could not be established in 23% of patients. Silicosis and chronic alcoholism were observed in 22% of patients with relapse.

Adolescent↗
PubMed2006

Interactions between microbial iron reduction and metal geochemistry: effect of redox cycling on transition metal speciation in iron bearing sediments.

Microbial iron reduction is an important biogeochemical process that can affect metal geochemistry in sediments through direct and indirect mechanisms. With respectto Fe(III) (hydr)oxides bearing sorbed divalent metals, recent reports have indicated that (1) microbial reduction of goethite/ferrihydrite mixtures preferentially removes ferrihydrite, (2) this process can incorporate previously sorbed Zn(II) into an authigenic crystalline phase that is insoluble in 0.5 M HCl, (3) this new phase is probably goethite, and (4) the presence of nonreducible minerals can inhibit this transformation. This study demonstrates that a range of sorbed transition metals can be selectively sequestered into a 0.5 M HCl insoluble phase and that the process can be stimulated through sequential steps of microbial iron reduction and air oxidation. Microbial reduction experiments with divalent Cd, Co, Mn, Ni, Pb, and Zn indicate that all metals save Mn experienced some sequestration, with the degree of metal incorporation into the 0.5 M HCl insoluble phase correlating positively with crystalline ionic radius at coordination number = 6. Redox cycling experiments with Zn adsorbed to synthetic goethite/ferrihydrite or iron-bearing natural sediments indicate that redox cycling from iron reducing to iron oxidizing conditions sequesters more Zn within authigenic minerals than microbial iron reduction alone. In addition, the process is more effective in goethite/ferrihydrite mixtures than in iron-bearing natural sediments. Microbial reduction alone resulted in a -3x increase in 0.5 M HCl insoluble Zn and increased aqueous Zn (Zn-aq) in goethite/ferrihydrite, but did not significantly affect Zn speciation in natural sediments. Redox cycling enhanced the Zn sequestration by approximately 12% in both goethite/ferrihydrite and natural sediments and reduced Zn-aq to levels equal to the uninoculated control in goethite/ferrihydrite and less than the uninoculated control in natural sediments. These data suggest that in situ redox cycling may serve as an effective method for

Ferric Compounds↗
PubMed1996

Synthesis and structure-activity relationships of 2-pyridones: a novel series of potent DNA gyrase inhibitors as antibacterial agents.

Two novel series of 2-pyridones were synthesized by transposition of the nitrogen of 4-quinolones to the bridgehead position. This subtle interchange of the nitrogen atom with a carbon atom yielded two novel heterocyclic nuclei, pyrido[1,2-alpha]pyrimidine and quinolizine, which had not previously been evaluated as antibacterial agents and were found to be potent inhibitors of DNA gyrase. Quinolizines with a methyl group at the 9-position such as (S)-45a (ABT-719) demonstrate exceptional broad spectrum antibacterial activity. Most notably, they are active against resistant bacteria such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of enterococci, and ciprofloxacin-resistant organisms. In addition, 2-pyridones also possess favorable physiochemical and pharmacokinetic properties. These 2-pyridones were synthesized from the commercially available starting materials by 10-17 linear transformations. The structure of an adduct yielded by this sequence, (S)-45a (ABT-719), was determined by X-ray crystallographic analysis.

Animals↗
PubMedDate not supplied

Waterline biofilm and the dental treatment facility: a review.

Biofilms are well-organized communities of cooperating microorganisms that can include bacteria, protozoa, diatoms, and fungi. Surveys of dental unit waterlines (DUWLs) indicate that biofilm formation is a universal problem and that environmental and human-derived opportunistic pathogens can be cultured consistently from biofilms retrieved from DUWLs and other dental devices. Although the health risks presented by waterline bacterial colonization have yet to be adequately addressed, professional and ethical considerations indicate that steps should be taken to improve the quality of DUWLs. To address these concerns, the Council on Scientific Affairs of the ADA recently published a list of products cleared by the FDA to control dental waterline contamination. The goal of this article is to increase the awareness of potential health risks posed by biofilm formation and provide information on techniques and devices designed to control the microbial contamination of DUWLs.

Bacteria↗