Cancer, 2004 Oct 15, 101(8), 1866 - 72 Role of hydrochloric acid in the treatment of central venous catheter infections in children with cancer; Barbaric D et al.; BACKGROUND: The use of central venous catheters (CVCs) in pediatric cancer patients is associated with substantial risk of producing sepsis . The treatment of catheter-related infections has generally consisted of antibiotic administration with or without catheter removal . The authors report the first published experience using intraluminal hydrochloric acid (HCl) instillation as an adjunct to systemic antimicrobials in the management of catheter-related infections in children with cancer . METHODS: All episodes of intraluminal instillation of 2 M HCl in oncology patients at The Children's Hospital at Westmead between December 1994 and August 2000 were reviewed . Episodes of HCl use were identified from a prospectively maintained infection data base . Successful treatment was defined as no recurrence of infection and no need for CVC removal in the 100 days after HCl administration . RESULTS: Forty-two episodes of HCl instillation were evaluated that occurred in children in whom blood cultures remained positive despite 48 hours of appropriate, systemic antibiotics and formed the basis of this review . All patients had in situ a surgically placed, subcutaneously tunneled CVC . The combination of systemic antibiotic therapy and HCl instillation was successful in eradicating infection in 67% of infection episodes in this patient cohort . The catheter salvage rate was 83% in patients with isolated Gram-negative infections, 75% in patients with isolated fungemia, and 50% in patients with isolated Gram-positive infections . CONCLUSIONS: The results suggest that HCl instillation is a useful adjunct to systemic antibiotic therapy, enabling both catheter salvage and eradication of antibiotic-refractory catheter-related infection. Curr Opin Crit Care, 2004 Oct, 10(5), 369 - 74 Severe community-acquired pneumonia; Alvarez-Lerma F et al.; PURPOSE OF REVIEW: Community-acquired pneumonia remains a prevalent and potentially life-threatening infection . In general, the disease is considered severe when inpatient care including ICU admission is required, and this often suggests a poorer prognosis . Severe community-acquired pneumonia continues to be an important subject of research from different perspectives, including assessment of illness severity, etiology, diagnostic tests, and treatment options . The aim of this descriptive review is to comment on the results of the relevant original articles in this area published since April 1, 2003 . RECENT FINDINGS: The main themes in the literature covered by the review include the time course of serum concentrations of different markers of the inflammatory response, validation of severity scores to optimize hospital and ICU admission, outcome improvement (duration of therapy and optimal dosing, time to antibiotic administration, adequate initial treatment, and the impact of positive microbiological diagnosis on management and prognosis), and the efficacy of new antimicrobials . SUMMARY: The usefulness of inflammatory markers to assess the outcome of the disease is unclear . Data on severity scores are conclusive and different validated and simple predictive rules are available for the classification of patients into risk classes . Therapeutic strategies that have been investigated confirm the impact of adequate empiric antibiotic treatment on clinical outcome and the equivalence between short and long courses in the duration of therapy . A definitive beneficial effect of early administration of antimicrobials or the knowledge of the etiology of pneumonia on the clinical course of the disease has not been demonstrated . Adv Exp Med Biol, 2004, 554, 11 - 25 Human milk proteins: key components for the biological activity of human milk; Lonnerdal B; Human milk contains a wide array of proteins that provide biologic activities ranging from antimicrobial effects to immunostimulatory functions . Proteins like lactoferrin, secretory IgA, kappa-casein, lactoperoxidase, haptocorrin, lactadherin and peptides formed from human milk proteins during digestion can inhibit the growth of pathogenic bacteria and viruses and therefore protect against infection . At the same time, proteins like lactoferrin, bile-salt stimulated lipase, haptocorrin, kappa-casein, and folate-binding protein can facilitate the absorption of nutrients in the neonatal gut . However, the proteins in human milk themselves also provide adequate amounts of essential amino acids to the growing infant . This suggests a highly adapted digestive system, which allows the survival of some proteins and peptides in the upper gastrointestinal tract, while still allowing amino acid utilization from these proteins further down in the gut . It is now possible to produce recombinant human milk proteins in transgenic plants and animals, which makes it possible to further study the bioactivity of these proteins . Provided these proteins can be produced in large scale at low cost, that they show biologic activity and pose no safety concerns, it may be possible to add some human milk proteins to infant diets, such as formula and complementary foods . Human milk proteins produced in rice or potatoes, for example, could be added without much purification, because these staples commonly are used in weaning foods . Thus, some qualities provided by human milk may be included into other diets, although it is highly unlikely that all unique components of human milk can be copied this way. Mol Divers, 2004, 8(3), 271 - 80 Cross-reactivity of T lymphocytes in infection and autoimmunity; Kamradt T et al.; T helper (Th) lymphocytes mediate critical effector and regulatory functions in infectious, allergic, or autoimmune diseases . Th cells possess clonal receptors that recognize antigenic peptides that are complexed with self-molecules of the major histocompatibility complex (MHC) on the surface of antigen presenting cells . An organism's repertoire of T cell receptors must be broad enough to recognize any possible microbial antigen . At the same time, tissue destruction resulting from the attack of autoreactive T lymphocytes that recognize self-peptides must be avoided . It was therefore believed that the immune system could distinguish between self and non-self antigens . This hypothesis was supported by several lines of evidence, including the seemingly exquisite specificity of immune responses . What, then, triggers autoaggressive attacks by the immune system? Clinical and epidemiological observations strongly suggest a link between infection and autoimmunity . A popular hypothesis considers autoimmunity as a side effect of antimicrobial immune responses . Cross-reactive T cells, capable of recognizing both microbial and self-peptides, have been prime suspects as instigators of autoimmunity ever since computerized data base searches revealed astonishing sequence homologies between microbial and self-peptides . Here we review recent data that show a previously unexpected degeneracy of antigen recognition by T cells . It has become clear that each individual T cell receptor can recognize a large number of different ligands . Furthermore, structural criteria rather than sequence homology dictate the antigen recognition process . Thus, the idea that cross-reactivity per se would cause autoimmune disease is most likely too simple . Instead, a variety of different molecular mechanisms dictate the immunological outcome of ligand recognition by T cells. Am J Kidney Dis, 2004 Oct, 44(4), 591 - 603 Antimicrobial agents to prevent peritonitis in peritoneal dialysis: a systematic review of randomized controlled trials; Strippoli GF et al.; BACKGROUND: A large proportion (15% to 50%) of the end-stage renal disease population are on peritoneal dialysis (PD) . The major limitation is peritonitis, which leads to technique failure, hospitalization, and increased mortality . Oral, nasal, and topical antibiotic prophylaxis; exit-site disinfectants; and other antimicrobial interventions are used to prevent it . This study was conducted to assess what evidence supports these approaches . METHODS: The Cochrane CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for randomized trials of antimicrobial agents in patients on PD . Two reviewers extracted data on the number of patients with 1 or more episodes and rates of peritonitis and exit-site and tunnel infection, catheter removal and/or replacement, technique failure, antibiotic toxicity, and all-cause mortality . Analysis was by means of a random-effects model, and results are expressed as relative risk (RR) and 95% confidence intervals (CI) . RESULTS: Nineteen eligible trials (1,949 patients) were identified . Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (1 trial; 2,716 patient-months; RR, 0.58; 95% CI, 0.40 to 0.85), but not peritonitis rate (1 trial; 2,716 patient-months; RR, 0.84; 95% CI, 0.44 to 1.60) . Perioperative intravenous antibiotic therapy compared with no treatment significantly reduced the risk for early peritonitis (4 trials; 335 patients; RR, 0.35; 95% CI, 0.15 to 0.80), but not exit-site and tunnel infection (3 trials; 114 patients; RR, 0.32; 95% CI, 0.02 to 4.81) . CONCLUSION: Based on 1 study, nasal mupirocin reduces exit-site and tunnel infection, but not peritonitis . Based on 4 studies, preoperative intravenous prophylaxis reduces early peritonitis, but not exit-site and tunnel infection . No other antimicrobial intervention has proven efficacy . Given the large number of patients on PD therapy and the importance of peritonitis, the lack of adequately powered randomized trials to inform decision making about strategies to prevent peritonitis is striking. Microb Drug Resist, 2004 Fall, 10(3), 204 - 8 Antimicrobial resistance in Brachyspira pilosicoli with special reference to point mutations in the 23S rRNA gene associated with macrolide and lincosamide resistance; Karlsson M et al.; A point mutation in the 23S rRNA gene causes macrolide and lincosamide resistance in Brachyspira hyodysenteriae . The possible occurrence of a similar mutation in Brachyspira pilosicoli was studied and the MICs of six antimicrobial agents for Swedish field isolates of B . pilosicoli were determined . Of 10 isolates with high MICs of macrolide and lincosamide antibiotics, six had a mutation in nucleotide position 2058 or 2059 in the 23S rRNA gene as compared to the wild type of Escherichia coli, whereas none of 10 tylosin-susceptible isolates were mutated in this region . The mutations found in position 2058 were A --> T transversions, and in position 2059 either A --> G transitions or A --> C transversions . The MICs at which 90% of the B . pilosicoli field isolates were inhibited by tylosin, erythromycin, clindamycin, virginiamycin, tiamulin, and carbadox, were >256, >256, >4, 4, 2, and 0.125 microg/ml, respectively . In conclusion, point mutations in positions 2058 and 2059 of the 23S rRNA gene can cause macrolide and lincosamide resistance in B . pilosicoli . Macrolide resistance is widespread among Swedish field isolates of B . pilosicoli . Notably also a few isolates with elevated MICs of tiamulin were found . Copyright Mary Ann Liebert, Inc. AORN J, 2004 Aug, 80(2), 225 - 34 Hand scrub products--performance requirements versus clinical relevance; Paulson DS; The US Food and Drug Administration regulates antimicrobial label claims for surgical hand scrub products . Surgical scrub products must meet preset performance criteria for immediate, persistent, and residual antimicrobial properties . Although the test currently used to validate surgical hand scrub products is rigorous in research methodology, it lacks practical clinical relevance. Hepatology, 2004 Oct, 40(4), 925 - 32 Peptide antibiotic human beta-defensin-1 and -2 contribute to antimicrobial defense of the intrahepatic biliary tree; Harada K et al.; Human beta-defensins (hBDs) are important antimicrobial peptides that contribute to innate immunity at mucosal surfaces . This study was undertaken to investigate the expression of hBD-1 and hBD-2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell lines (2 consisting of biliary epithelial cells and 2 cholangiocarcinoma cells) . In addition, hBD-1 and hBD-2 were assayed in specimens of bile . hBD-1 was nonspecifically expressed immunohistochemically in intrahepatic biliary epithelium and hepatocytes in all patients studied, but expression of hBD-2 was restricted to large intrahepatic bile ducts in 8 of 10 patients with extrahepatic biliary obstruction (EBO), 7 of 11 with hepatolithiasis, 1 of 6 with primary biliary cirrhosis (PBC), 1 of 5 with primary sclerosing cholangitis (PSC), 0 of 6 with chronic hepatitis C (CH-C), and 0 of 11 with normal hepatic histology . hBD-2 expression was evident in bile ducts exhibiting active inflammation . Serum C reactive protein levels correlated with biliary epithelial expression of hBD-2 . Real-time PCR revealed that in all of 28 specimens of fresh liver, including specimens from patients with hepatolithiasis, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliary epithelium of patients with hepatolithiasis . Immunobloting analysis revealed hBD-2 protein in bile in 1 of 3 patients with PSC, 1 of 3 with PBC, and each of 6 with hepatolithiasis; in contrast, hBD-1 was detectable in all bile samples examined . Four cultured biliary epithelial cell lines consistently expressed hBD-1; in contrast these cell lines did not express hBD-2 spontaneously but were induced to express hBD-2 by treatment with Eschericia coli, lipopolysaccharide, interleukin-1beta or tumor necrosis factor-alpha . In conclusion, these findings suggest that in the intrahepatic biliary tree, hBD-2 is expressed in response to local infection and/or active inflammation, whereas hBD-1 may constitute a preexisting component of the biliary antimicrobial defense system. Biochem Biophys Res Commun, 2004 Oct 22, 323(3), 1024 - 31 Damaged DNA binding protein 1 in Drosophila defense reactions; Takata K et al.; We have focused attention on functions of Drosophila damaged DNA binding protein 1 (D-DDB1) in Drosophila hematopoiesis and previously reported that its whole body dsRNA over-expression using a GAL4-UAS targeted expression system results in melanotic tumors and complete lethality . Since the lesions appear to arise as a normal and heritable response to abnormal development, forming groups of cells that are recognized by the immune system and encapsulated in melanized cuticle, D-DDB1 appears to be an essential development-associated factor in Drosophila . To probe the possibility that it contributes to hemocyte development, we used a collagen promoter-GAL4 strain to over-express dsRNA of D-DDB1 in Drosophila hemocytes . The D-DDB1 gene silencing caused melanotic tumors and mortality at the end of larval development . Similarly, it interfered with melanization and synthesis of antimicrobial peptides . Transgenic flies with D-DDB1 gene silencing were found to accumulate abnormal large blood cells, reminiscent of human leukemia, suggesting that D-DDB1 has functions in hemocyte development. Biochem Biophys Res Commun, 2004 Oct 22, 323(3), 721 - 7 Avian antimicrobial peptides: the defense role of beta-defensins; Sugiarto H et al.; Avian antimicrobial peptides, classified as beta-defensins, have been identified from bloods of chicken, turkey, and ostrich; epithelial cells of chicken and turkey; and king penguin stomach contents . Beta-defensins are a family of antimicrobial peptides characterized by six cysteine residues forming beta-defensin motifs that are also found in bovine, ovine, pig, and human . These peptides are active against a wide range of microorganisms including Gram-positive and Gram-negative bacteria, fungi, and yeast . Analysis of evolutionary relationships of vertebrate beta-defensins showed that there might be a common ancestral gene between avian and other mammalian peptides . This ancient gene may have been passed down and evolved from species older than the oldest living birds, forming a beta-defensin-like precursor molecule . This review describes potential applications of these peptides in health care products. Phytochemistry, 2004 Aug, 65(16), 2373 - 8 Xanthones from a microfungus of the genus Xylaria; Healy PC et al.; Chemical investigations of a microfungus Xylaria sp . isolated from the Australian rainforest tree Glochidion ferdinandi have afforded two new natural products, 2-hydroxy-6-methyl-8-methoxy-9-oxo-9H-xanthene-1-carboxylic acid (1) and 2-hydroxy-6-hydroxymethyl-8-methoxy-9-oxo-9H-xanthene-1-carboxylic acid (2) . Compound 1 has previously been synthesised but only partially characterised . Methylation of 1 using diazomethane afforded the crystalline compound 2,8-dimethoxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester (3), whose structure was determined by single crystal X-ray analysis . This paper reports the full spectroscopic characterisation of compounds 1-3 by NMR, UV, IR and MS data . All compounds were inactive in a brine shrimp lethality assay and several antimicrobial screens. Int J Antimicrob Agents, 2004 Oct, 24(4), 311 - 4 Use of veterinary antimycotic products in the UK, 1998-2002; Goodyear KL et al.; The UK Government is committed to promoting the responsible use of antimicrobial products . As part of this commitment, the Veterinary Medicines Directorate (VMD), an agency of the Department for Environment, Food and Rural Affairs, collates and publishes reports detailing the quantities of veterinary antimicrobial products sold by the pharmaceutical companies in the UK . To date, these reports have focussed on antibacterials and antiprotozoals . This paper acts as a baseline by summarising, for the first time, the sales of veterinary antimycotic products in the UK over a five-year-period, 1998-2002, and looks at trends in sales of different groups of products . It is hoped that information of sales of these products will contribute to knowledge of the potential for overall development of antimicrobial resistance in the veterinary field. Curr Drug Targets Infect Disord, 2004 Sep, 4(3), 193 - 202 Macrolide resistance based on the Erm-mediated rRNA methylation; Maravic G; Macrolide, lincosamide and streptogramin B (MLSB) antibiotics are extensively used for the treatment of wide variety of clinically important Gram-positive bacteria . MLSB antibiotics inhibit protein biosynthesis by targeting the peptidyl transferase centre within the 50S ribosomal subunit . The most widespread mechanism of bacterial resistance to MLSB antibiotics, reported early after their introduction into clinical practice is the modification of the target site exhibited by a family of rRNA methyltransferases designated Erm . Using S-adenosyl-L-methionine, Erm enzymes catalyze mono- or dimethylation of a specific adenine residue in the 23S rRNA . The methyl group sterically hinders the MLSB binding site and disrupts the hydrogen bonding between the macrolides and the rRNA, thus rendering bacteria resistant . This review summarizes the current understanding of Erm-mediated resistance, in light of high-resolution structural data of bacterial ribosome and with specific focus on the results of recent genetic, biochemical and structural studies of Erm methyltransferases and their cognate rRNA substrate . Although many features of MLSB resistance remain indistinct, the present knowledge can now serve as the guidance for development of both new antimicrobial drugs and potential inhibitors of Erm enzymes, hence providing a new lead to solve the urgent problem of the macrolide resistance based on the ribosome methylation. Curr Pharm Des, 2004, 10(23), 2891 - 905 Antimicrobial peptides: mediators of innate immunity as templates for the development of novel anti-infective and immune therapeutics; Hiemstra PS et al.; Antimicrobial molecules are ancient and essential small cationic molecules of the host defence system which are found in a wide variety of species . They display antimicrobial activity against a wide range of bacteria, fungi and viruses, an activity that has been mostly attributed to the disruption of microbial membranes . In this article, we will review the "classical" functions of 3 classes of antimicrobial molecules, namely defensins, cathelicidins, and the four-disulfide core proteins secretory leukocyte proteinase inhibitor (SLPI) and elafin . In addition to the study of their expression in a variety of cell types and the regulation of their production, we will also describe novel properties of these molecules that have been highlighted by recent studies . These include their ability to chemoattract a variety of inflammatory, immune and other cell types (neutrophils, macrophages, monocytes, lymphocytes, mast cells, epithelial cells) in vitro and in vivo . In addition, we will discuss the potential use of these newly discovered properties for therapeutic or vaccination purposes, using protein- or gene-transfer based methodologies . Finally, we will examine in an extensive fashion the strategies used by microorganisms to circumvent and subvert host defence mechanisms, such as the modifications of cell membranes and walls, the secretion of inactivating proteins and proteases and the down-regulation of expression of antimicrobial molecules . Increased understanding of the mechanisms used by both the host and the microbes to 'win the battle' may ultimately lead to new therapeutic strategies aimed to treat infectious diseases. Curr Pharm Des, 2004, 10(24), 2935 - 50 Radiolabeled compounds in diagnosis of infectious and inflammatory disease; Bleeker-Rovers CP et al.; Nuclear medicine offers powerful noninvasive techniques for visualization of infectious and inflammatory disorders using whole body imaging enabling the determination of both localization and number of inflammatory foci . A wide variety of approaches depicting the different stages of the inflammatory response have been developed . Non-specific radiolabeled compounds, such as 67Ga-citrate and radiolabeled polyclonal human immunoglobulin accumulate in inflammatory foci due to enhanced vascular permeability . Specific accumulation of radiolabeled compounds in inflammatory lesions results from binding to activated endothelium (e.g . radiolabeled anti-E-selectin), the enhanced influx of leukocytes (e.g . radiolabeled autologous leukocytes, anti-granulocyte antibodies or cytokines), the enhanced glucose-uptake by activated leukocytes (18F-fluorodeoxyglucose) or direct binding to micro-organisms (e.g . radiolabeled ciprofloxacin or antimicrobial peptides) . Scintigraphy using autologous leukocytes, labeled with 111In or 99mTc, is still considered the "gold standard" nuclear medicine technique for the imaging of infection and inflammation, but the range of radiolabeled compounds available for this indication is still expanding . Recently, positron emission tomography with 18F-fluorodeoxyglucose has been shown to delineate various infectious and inflammatory disorders with high sensitivity . New developments in peptide chemistry and in radiochemistry will result in specific agents with high specific activity . A gradual shift from non-specific, cumbersome or even hazardous approaches to more sophisticated, specific approaches is ongoing . In this review, the different approaches to scintigraphic imaging of infection and inflammation, already in use or under investigation, are discussed. Mini Rev Med Chem, 2004 Sep, 4(7), 747 - 56 Inhibitors of types I and II dehydroquinase; Le Sann C et al.; Inhibitors of varying potency have been developed for types I and II 3-dehydroquinate dehydratase (dehydroquinase), enzymes from the shikimate and quinate pathways that catalyse the dehydration of dehydroquinate to dehydroshikimate . These inhibitors have resulted from enzyme mechanistic studies and from the direct search for enzyme inhibitors with herbicidal, fungicidal or antimicrobial potential . This review discusses the design of the various inhibitors that have been produced so far and some structure-activity relationships . The majority of these inhibitors are based on dehydroquinate analogues, although some work has also been carried out on dehydroshikimate and bissulfonamides . Some discussion is also presented on advances in the synthesis of these types of compounds. Curr Drug Targets Inflamm Allergy, 2004 Sep, 3(3), 237 - 42 Potential role of antibiotics in the treatment of asthma; Blasi F et al.; Although the role of antibiotic treatment in asthma is still disputed, clinical use of antimicrobials in this setting is more widespread than warranted on the basis of indications in the literature . Viral upper respiratory tract infections are known to be involved in asthma exacerbations . More recently, evidence of Mycoplasma pneumoniae and Chlamydia pneumoniae involvement in asthma attacks has been reported both in adult and paediatric populations . These pathogens are also involved in chronic asthma, and both in vitro and animal model studies indicate that atypical agents may play a role in the pathogenesis of the disease . Recent studies on asthma patients with evidence of atypical infection suggest that specific antimicrobial treatment (basically macrolides or fluoroquinolones) may confer additional advantages compared to standard therapy alone . Furthermore, a considerable amount of data has been gathered describing additional effects associated with macrolide treatment (reduced bronchial hyper-responsiveness, altered cytokine production, etc.) . These non-antimicrobial effects have been defined as "anti-inflammatory activity" . Should this information be confirmed, the use of macrolides in patients with asthma may be twofold: eradication of occult atypical infection; and reduction in the airway inflammation burden . Future lines of research in this field should attempt to determine whether specific antibiotic treatment may alter the natural history of asthma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2004 Aug, 26(4), 351 - 3 {Bacterial resistance and study of new antibiotics}; Xiao CL et al.; Drug-resistant (including multidrug-resistant) bacteria increase continuously with the wide use of antibiotics, which have seriously threatened the human health . It is an important way to fight against drug-resistance by screening and developing novel drugs based on the various mechanisms of the bacterial drug tolerances . Meanwhile, the basic research related to the new drug R . & D . and studies on the new screening methods for the antimicrobial agents should be taken seriously and strengthened, so as to accelerate the process of finding new drugs and meet the challenge of new pathogens and new drug-resistant strains. Inflammation, 2004 Apr, 28(2), 53 - 8 Study on myeloperoxidase role in antituberculous defense in the context of cytokine activation; Koziol-Montewka M et al.; Myeloperoxidase (MPO), next to the NO synthase2 (NOS2), and NADPH oxidase, is the key enzyme of the oxidative burst responsible for the antimicrobial immunity . Because MPO participates in the eradication of Mycobacterium tuberculosis in the in vitro model and the extracellular enzyme may activate cells to cytokine synthesis, we investigated the changes in the enzyme concentration in serum of patients with active pulmonary tuberculosis (TB) and correlations between MPO and TNF-alpha, IFN-gamma, and IL-12 . To our knowledge, our study is the first to indicate the involvement of MPO during active TB which manifested itself in the significant increase in serum concentration . The statistically significant elevation of TNF-alpha and IL-12 was also noticed in serum of the TB positive group . The statistical analysis revealed no correlation between the cytokine and MPO production in the studied cases . However, the increase in TNF-alpha and IL-12 serum concentration with simultaneous elevation of serum MPO in the group of the highest enzyme concentration may imply that correlation between the enzyme and the cytokines should not be excluded . Our study suggests possible involvement of MPO in the antituberculous, immunological response, and implies its connection with TNF-alpha and IL-12 activation. J Infect Dis, 2004 Oct 15, 190(8), 1438 - 47 Epub 2004 Sep 10. Development of Vgamma2Vdelta2+ T cell responses during active mycobacterial coinfection of simian immunodeficiency virus-infected macaques requires control of viral infection and immune competence of CD4+ T cells; Shen L et al.; Vgamma2Vdelta2+ T cells play a role in antimicrobial responses . It is unknown whether adaptive Vgamma2Vdelta2+ T cell responses during active mycobacterial coinfection of human immunodeficiency virus-infected humans can be generated during effective antiretroviral treatment . Here, simian immunodeficiency virus (SIV)mac-infected macaques previously exposed to bacille Calmette-Guerin (BCG) were reinfected with BCG, were treated either with tenofovir or tenofovir plus indinavir, and were assessed for the development of Vgamma2Vdelta2+ T cell responses during active BCG coinfection . A restored capacity of Vgamma2Vdelta2+ T cells to undergo major expansions and pulmonary migration during active BCG coinfection was detected after simultaneous BCG reinfection and treatment with tenofovir of the SIVmac-infected macaques . Interestingly, a restored expansion of Vgamma2Vdelta2+ T cells in the SIVmac/BCG-coinfected macaques was detectable, even though antiretroviral treatment was initiated 1 month after BCG reinfection . Importantly, the restored expansion of Vgamma2Vdelta2+ T cells coincided with increases in numbers of purified protein derivative-specific interferon- gamma -producing CD4+ T cells and increases in the magnitude of their proliferative responses . In contrast, the SIVmac-infected control macaques exhibited diminished responses of Vgamma2Vdelta2+ T cells and mycobacterium-specific CD4+ T cells during active BCG coinfection . Our results suggest that the development of adaptive immune responses of phosphoantigen-specific Vgamma2Vdelta2+ T cells during active mycobacterium/HIV coinfection requires control of viral infection and immune competence of peptide-specific CD4+ T cells . Clin Pediatr (Phila), 2004 Sep, 43(7), 631 - 6 The relationship of breastfeeding to antimicrobial exposure in the first year of life; Flores MS et al.; We assessed the relationship between breastfeeding and antimicrobial use in the first year of life in healthy infants by surveying a military population of healthy term infants with questionnaires obtained at the 6-month and 12-month well-baby visits . Breastfed (BF) babies spent 48% as much time receiving antimicrobials by 6 months of age and 47.4% by 12 months of age as compared to formula-fed peers . Breastfed babies also showed significant differences in use of second-line agents at both 6 months (BF=5.5%, Non-BF=19%) and 12 months (19% BF, nonBF=36.9%) . These results suggest that breastfeeding decreases exposure of infants to antimicrobials throughout the first year of life and also decreases use of second-line antibiotics in the first year of life. Nat Rev Microbiol, 2004 Oct, 2(10), 820 - 32 Antimicrobial reactive oxygen and nitrogen species: concepts and controversies; Fang FC; Phagocyte-derived reactive oxygen and nitrogen species are of crucial importance for host resistance to microbial pathogens . Decades of research have provided a detailed understanding of the regulation, generation and actions of these molecular mediators, as well as their roles in resisting infection . However, differences of opinion remain with regard to their host specificity, cell biology, sources and interactions with one another or with myeloperoxidase and granule proteases . More than a century after Metchnikoff first described phagocytosis, and more than four decades after the discovery of the burst of oxygen consumption that is associated with microbial killing, the seemingly elementary question of how phagocytes inhibit, kill and degrade microorganisms remains controversial . This review updates the reader on these concepts and the topical questions in the field. J Dairy Sci, 2004 Oct, 87(10), 3132 - 7 Occurrence of antibiotic residues in milk from Manchega ewe dairy farms; Yamaki M et al.; Ewe milk samples from different ovine dairy farms from the Castilla-La Mancha region of Spain were collected from bulk tanks to estimate the occurrence of antibiotic residues in raw and heated (82 degrees C, 10 min) milk by the Delvotest SP test . The month of collection, somatic cell counts, and bacteriology were analyzed and examined by means of a logistic regression model . The screening of a total of 2686 raw milk samples showed 1.7% "positive" and 2.1% "doubtful" results, which decreased after heating treatment to 1.3% and 0.4%, respectively . "Positive" and "doubtful" samples were identified by penicillinase and p-aminobenzoic acid solutions, and the majority of them corresponded to antimicrobials different than beta-lactams or sulfonamides . By applying a logistic regression model, a significant effect of month of collection and bacteriology was observed in the initial screening and after the heat treatment . The highest percentages of "positive plus doubtful" results were observed in late summer-early autumn . A slight peak was also observed in spring in raw milk samples . Bacteriology was positively correlated with "positive plus doubtful" results. Br J Dermatol, 2004 Sep, 151(3), 534 - 9 Dermcidin is constitutively produced by eccrine sweat glands and is not induced in epidermal cells under inflammatory skin conditions; Rieg S et al.; BACKGROUND: Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms . In human skin two classes of AMPs-the beta-defensins and the cathelicidins-are produced by keratinocytes primarily under inflammatory conditions . In contrast, dermcidin (DCD), a recently discovered AMP with broad-spectrum activity, is expressed in eccrine sweat glands and transported via sweat to the epidermal surface . OBJECTIVES: To investigate whether DCD expression is induced under inflammatory conditions in epidermal keratinocytes . METHODS: Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by immunohistochemistry using a polyclonal anti-DCD antiserum . We also examined whether DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells . RESULTS: Whereas DCD was constitutively expressed in eccrine sweat glands of all skin biopsies, we found that, independent of the type of the inflammatory skin lesion, DCD protein expression was not induced in human epidermal keratinocytes . In contrast, beta-defensin 2 was expressed in epidermal keratinocytes of inflammatory human skin, but not in keratinocytes of healthy human skin . Upon stimulation of the cultured cells with 12-O-tetradecanoyl-phorbol-13-acetate, tumour necrosis factor-alpha, lipopolysaccharide or H2O2, DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocytes, but was detected in MeWo and SKMEL28 melanoma cells . CONCLUSIONS: These results indicate that, unlike human cathelicidins and beta-defensins which are inducible peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin . By modulating surface colonization, DCD may help to prevent local and systemic invasion of pathogens. Dtsch Med Wochenschr, 2004 Sep 17, 129(38), 1987 - 92 Antibiotic use in Germany and European comparison; De With K et al.; In view of increasing rates of antibiotic resistance worldwide and decreased research and development of new antibacterial compounds, programmes helping to better understand the complex relationship between antibiotic consumption and emergence of resistance have gained importance . Consequently, in addition to increased support for research projects that establish prospective surveillance and evaluation of antibiotic resistance and antimicrobial drug use, the EU has passed directives addressing political leadership in this respect . Information on antibiotic use in Germany is now available from databases independent from cost-oriented market research studies . This information allows estimation of antibiotic use in ambulatory and hospital care as compared with to other EU countries . According to results of current projects, the frequency of national antibiotic use in ambulatory care in Germany (4948 defined daily doses per 1000 population per year) falls within the lower third of EU countries . Upper boundaries in regional variation in antibiotic use are still much lower than values for high-use countries like France, Spain and Portugal . Hospital antibiotic use, in contrast, appears to be in the range of that reported for other countries . However, only rough estimates of hospital antibiotic use are available for Germany as well as most other EU countries due to data usually derived from non-representative hospital sampling. Int J Qual Health Care, 2004 Oct, 16(5), 367 - 73 Practice variation in perioperative antibiotic use in Japan; Sekimoto M et al.; OBJECTIVE: Under the fee-for-service system, the overuse and misuse of perioperative antibiotics have become serious concerns in Japan . The objective of the present study is to investigate practice variations of perioperative antimicrobial prophylaxis between and within hospitals, and to identify any opportunities for improvement . METHODS: We polled 319 surgeons in six specialties employed by 11 teaching hospitals in Japan . We developed questionnaires with vignettes, asking physicians about their practice of antimicrobial prophylaxis in six surgical procedures (gastrectomy, hysterectomy, cataract surgery, clipping of cerebral aneurysm, hip fracture surgery, and coronary artery bypass graft) and utilization of institutional clinical pathways . RESULTS: Average durations of prophylaxis varied by procedure, from 1.6 days for cataract surgery to 5.8 days for clipping surgery . Variation was also observed between institutions for the same procedure, e.g . institutional averages for the duration of prophylaxis for gastrectomy ranged from 2.3 to 7 days . Large intra-institutional variation in prophylaxis duration and inconsistent use of clinical pathways were observed in the cases of gastrectomy, hip fracture surgery, and clipping surgery . At one hospital, 20% of physicians performing gastrectomy indicated the use of an institutional clinical pathway, and prophylaxis duration ranged from 3 to 6 days . For cataract surgery and hysterectomy, clinical pathways were universally applied and intra-institutional practice variation was small, yet prophylaxis duration varied widely between hospitals and third-generation cephalosporins were used extensively . Average length of prophylaxis for hysterectomy ranged from 1.8 to 6 days and 43% of respondents prescribed third-generation cephalosporins . CONCLUSIONS: In Japan, perioperative antimicrobial prophylaxis lacks standardization . Efforts to strengthen an evidence-based approach to antimicrobial prophylaxis need to be made a priority at both the national and institutional levels. J Endotoxin Res, 2004, 10(4), 261 - 8 Toll and Toll-9 in Drosophila innate immune response; Bettencourt R et al.; In both insects and mammals, members of the Toll receptor family play important roles in the initial events leading to the activation of immunity genes . The prototypic Toll in Drosophila appears to be activated by a host protein ligand after microbial stimulation . The cellular events and the biological response after Toll activation, however, require further investigation . We used transgenic Drosophila strains expressing NF-kappaB and Toll proteins to investigate innate immune response in whole larvae and dissected larval fat bodies . Substantial activation of antimicrobial peptide genes was observed after septic injury . To circumvent the contribution of injury-induced response, we used dissected larval fat bodies to show that commercially available microbial compounds were able to alter the cellular distribution of Toll . The results also demonstrate that complex cellular events, including receptor trafficking, likely take place after stimulation of the larval immune tissue . By genome-wide expression analysis, we further show that Toll and Toll-9 may utilize the same signaling pathway in activating many immunity genes . Thus, the innate immune response in Drosophila is regulated by complex mechanisms, which involve Toll and other Toll-related proteins. J Endotoxin Res, 2004, 10(4), 241 - 6 Toll-dependent and Toll-independent immune responses in Drosophila; Imler JL et al.; The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient . Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides . Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system . In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs. Br J Clin Pharmacol, 2004 Oct, 58(4), 419 - 28 European surveillance of antimicrobial consumption (ESAC): data collection performance and methodological approach; Vander Stichele RH et al.; BACKGROUND: Europe is a continent with strong public healthcare systems, but diverging antibiotic policies and resistance patterns . AIMS: To describe the performance and methodological approach in a retrospective data collection effort (1997-2001), through an international network of surveillance systems, aiming to collect publicly available, comparable and reliable data on antibiotic use in Europe . METHODS: A central multidisciplinary management team co-ordinated a network of national representatives, liasing with national data providers and bodies responsible for antibiotic policy . The data collected were screened for bias, using a checklist . We focused on detection bias in sample and census data; errors in assigning medicinal product packages to the Anatomical Therapeutic Chemical Classification (ATC); errors in calculations of defined daily doses (DDD) per package; bias by over-the-counter sales and parallel trade; and bias in ambulatory care (AC)/hospital care (HC) mix . Datasets were corrected after national feedback, and classified as valid; valid but with minor bias; not valid . RESULTS: Of the 31 participating countries, 21 countries delivered AC data suitable for cross-national comparison (14 for all 5 years) . Of these, 17 countries provided data on a quarterly basis for at least 1 year . For HC, 14 countries were able to deliver valid data (nine for all 5 years) . A valid estimate of the total exposure of national populations to human antibiotic consumption could be made in 17 countries . CONCLUSION: In cross-national comparisons of antibiotic consumption in Europe, methodological rigour in correcting for various sources of bias and checking the validity of ATC/DDD assignment is needed . Clin Microbiol Infect, 2004 Oct, 10(10), 917 - 21 An after-hours clinical liaison blood culture service--is it worth it? Fitzpatrick F, Turley M, Humphreys H, Smyth E. The impact of clinical liaison on therapy for positive after-hours blood cultures was evaluated . Of 223 positive blood cultures, no change in management occurred in 164 (73%) cases: 115 positive cultures were regarded as contaminants, and 49 patients were receiving appropriate therapy already . The results of microscopy or culture altered the antimicrobial management of 59 (27%) patients: therapy was altered on the basis of microscopy for 33 patients, and was altered for 26 patients when culture results were available . In total, 94 doses of inappropriate antibiotics were avoided . The main benefit of after-hours blood cultures was that laboratory results were available a day earlier, facilitating timely initiation of appropriate therapy and infection control procedures. Asian Pac J Cancer Prev, 2004 Jul-Sep, 5(3), 237 - 45 Allium vegetables in cancer prevention: an overview; Sengupta A et al.; The Allium genus includes approximately 500 species . Commonly used allium vegetables include garlic, onion, leeks, chives, scallions which are used all over the world in different delicacies . Some allium vegetables have been employed for millenia in the traditional medical practice to treat cardiovascular diseases . They have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents . In recent years, extensive research has focused on the anticarcinogenic potential of allium vegetables and their constituents, viz., allylsulfides and flavonoids (particularly quercetin which is present abundantly in onion) . Epidemiological studies have shown that higher intake of allium products is associated with reduced risk of several types of cancers . These epidemiological findings are well correlated with laboratory investigations . Organosulfur compounds present in Allium vegetables, are considered to be responsible for the beneficial effects of these herbs . Several mechanisms have been proposed to explain the cancer-preventive effects of Allium vegetables and related organosulfur compounds . These include inhibition of mutagenesis, modulation of enzyme activities, inhibition of DNA adduct formation, free-radical scavenging, and effects on cell proliferation and tumor growth . Although there is a large body of evidence supporting these mechanisms, they are still speculative, and further research is needed to support causality between such properties and cancer-preventive activity in experimental animals . This article reviews current knowledge concerning allium vegetables and cancer prevention. J Agric Food Chem, 2004 Sep 8, 52(18), 5598 - 605 Antimicrobial and antioxidant effects of milk protein-based film containing essential oils for the preservation of whole beef muscle; Oussalah M et al.; Milk protein-based edible films containing 1.0% (w/v) oregano, 1.0% (w/v) pimento, or 1.0% oregano-pimento (1:1) essential oils mix were applied on beef muscle slices to control the growth of pathogenic bacteria and increase the shelf life during storage at 4 degrees C . Meat and film were periodically tested during 7 days for microbial and biochemical analysis . The lipid oxidation potential of meat was evaluated by the determination of thiobarbituric reactive substances (TBARS) . The availability of phenolic compounds from essential oils was evaluated by the determination of total phenolic compounds present in the films during storage . Antioxidant properties of films during storage were also evaluated following a modified procedure of the N,N-diethyl-p-phenylenediamine colorimetric method . Oregano-based films stabilized lipid oxidation in beef muscle samples, whereas pimento-based films presented the highest antioxidant activity . The application of bioactive films on meat surfaces containing 10(3) colony-forming units/cm2 of Escherichia coli O157:H7 or Pseudomonas spp . showed that film containing oregano was the most effective against both bacteria, whereas film containing pimento oils seems to be the least effective against these two bacteria . A 0.95 log reduction of Pseudomonas spp . level, as compared to samples without film, was observed at the end of storage in the presence of films containing oregano extracts . A 1.12 log reduction of E . coli O157:H7 level was noted in samples coated with oregano-based films. J Neurosci Res, 2004 Oct 1, 78(1), 87 - 91 Failure of neuronal protection by inhibition of glial activation in a rat model of striatonigral degeneration; Stefanova N et al.; Previous studies in rodent models of neurodegenerative disorders have demonstrated that minocycline exerts neuroprotective effects unrelated to its antimicrobial action . The purpose of the present study was to analyze whether minocycline exhibits neuroprotective activity in a rat model of striatonigral degeneration (SND), the core pathology underlying levodopa-unresponsive parkinsonism associated with multiple system atrophy (MSA) . We observed no significant effect of minocycline on locomotor impairment in double-lesioned SND rats . Minocycline significantly suppressed astroglial and microglial activation (P < 0.01); however, 3'5'-monophosphate-regulated phosphoprotein (DARPP 32) immunohistochemistry revealed no significant differences in striatal lesion volume of minocycline-treated versus untreated control SND rats . Furthermore, there was no protection of nigral dopaminergic neurons in the double-lesion model . We conclude that despite its astrocytic and microglial suppression, minocycline failed to attenuate lesion-induced neuronal damage in the SND rat model . 2004 Wiley-Liss, Inc. Nat Rev Microbiol, 2004 Sep, 2(9), 739 - 46 Seeing is believing: the impact of structural genomics on antimicrobial drug discovery; Schmid MB; Over the past decade, the availability of complete microbial genome sequences has led to changes in the strategies that are used to search for novel anti-infectives . However, despite the identification of many new potential drug targets, novel antimicrobial agents have been slow to emerge from these efforts . In part, this reflects the long discovery and development times that are needed to bring new drugs to market and the bottlenecks at the stages of identifying good lead compounds and optimizing these leads into drug candidates . Structural genomics will hopefully provide opportunities to overcome these bottlenecks and populate the antimicrobial pipeline. Nat Rev Microbiol, 2004 Sep, 2(9), 727 - 38 Primate defensins; Lehrer RI; Defensins are endogenous, cysteine-rich antimicrobial peptides that contribute to host defence against bacterial, fungal and viral infections . There are three subfamilies of defensins in primates: alpha-defensins are most common in neutrophils and Paneth cells of the small intestine; beta-defensins protect the skin and the mucous membranes of the respiratory, genitourinary and gastrointestinal tracts; and theta-defensins, which are expressed only in Old World monkeys, lesser apes and orangutans, are lectins with broad-spectrum antiviral efficacy . Here, their discovery and recent advances in understanding their properties and functions are described. Nat Rev Microbiol, 2004 Sep, 2(9), 695 - 703 Passive antibody therapy for infectious diseases; Casadevall A et al.; Antibody-based therapies are currently undergoing a renaissance . After being developed and then largely abandoned in the twentieth century, many antibody preparations are now in clinical use . However, most of the reagents that are available target non-infectious diseases . Interest in using antibodies to treat infectious diseases is now being fuelled by the wide dissemination of drug-resistant microorganisms, the emergence of new microorganisms, the relative inefficacy of antimicrobial drugs in immunocompromised hosts and the fact that antibody-based therapies are the only means to provide immediate immunity against biological weapons . Given the need for new antimicrobial therapies and many recent technological advances in the field of immunoglobulin research, there is considerable optimism regarding renewed applications of antibody-based therapy for the prevention and treatment of infectious diseases. Scand J Infect Dis, 2004, 36(8), 607 - 9 Modulation of the human interleukin-12p40 response by a triazole antifungal derivative, itraconazole; Inoue H et al.; Some types of antimicrobial agents such as fosfomycin, clarithromycin, and erythromycin have been known to affect the host's immunological response . We investigated whether itraconazole (ITCZ) can modulate the serum cytokine levels (tumor necrosis factor (TNF-alpha, interleukin (IL)-10, IL-12p40) in both patients and healthy subjects . Serum samples were collected and TNF-alpha, IL-10 and IL-12p40 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) . We showed increased levels of IL-12p40 in patients treated with ITCZ . In healthy subjects, moreover, ITCZ treatment significantly increased the production of IL-12p40, but not TNF-alpha or IL-10 . These findings suggest that the effectiveness of ITCZ in the treatment of fungal infection may be due not only to its direct antifungal effect, but also to induction of an immunomodulative effect on the host defense systems by regulation of cytokine production. Scand J Infect Dis, 2004, 36(9), 636 - 8 Susceptibility of Mexican brucella isolates to moxifloxacin, ciprofloxacin and other antimicrobials used in the treatment of human brucellosis; Lopez-Merino A et al.; Brucellosis is a disease of domestic and wild animals that is transmitted to humans and exists worldwide . We assessed the in vitro activity of moxifloxacin, ciprofloxacin, tetracycline, doxicycline, rifampin, streptomycin and trimethoprim-sulfamethoxazole (TMP/SMX) against 97 Brucella strains isolated from clinical samples, animals and dairy products in Mexico . Fluoroquinolones showed an antibacterial activity similar to that of tetracyclines (MIC(90) 0.5) . Other drugs commonly used against brucellosis were less active, such as rifampin (MIC(90) 2.0 microg/ml) and streptomycin (MIC(90) 4.0 microg/ml) . TMP/SMX showed the poorest activity (MIC(90) 8.0 microg/ml) . Fluoroquinolones, either first-generation or the newer 8-methoxi derivatives, might be useful in the therapy of brucellosis, which remains to be assessed in clinical trials. J Microbiol Methods, 2004 Nov, 59(2), 173 - 9 Bacterial cytoplasmic membrane permeability assay using ion-selective electrodes; Ohmizo C et al.; We used K(+) and tetraphenylphosphonium (TPP(+)) electrodes simultaneously to evaluate the ability of antimicrobial peptides to form channels (or more generally to increase permeability) and to abolish membrane potential in bacterial cytoplasmic membranes in situ . Such evaluations are usually made independently by colorimetric monitoring of the hydrolysis of a chromogenic substrate by a cytoplasmic enzyme or by fluorimetric determination of membrane depolarization using a membrane potential-sensitive dye . In the present study, the K(+) electrode was used to evaluate channel-forming ability by monitoring the efflux of K(+) originally present in the cytoplasm of bacteria, while the TPP(+) electrode was used to examine membrane depolarization causing the efflux of TPP(+) accumulated in the cytoplasm of bacteria dependent on membrane potential . Thus, the combination of these two electrodes enabled us to clarify how the peptide-induced formation of ion channels is involved in disrupting the energy-generating system in situ. Biochem Biophys Res Commun, 2004 Oct 15, 323(2), 712 - 9 Antibiotic activity and structural analysis of the scorpion-derived antimicrobial peptide IsCT and its analogs; Lee K et al.; IsCT is a non-cell-selective antimicrobial peptide isolated from the scorpion Opisthacanthus madagascariensis that has potent cytolytic activity against both mammalian and bacterial cells . To investigate the structure-activity relationships of IsCT and to design novel peptide antibiotics with bacterial cell selectivity, we synthesized several analogs of IsCT and determined their three-dimensional structures in solution by 2D-NMR spectroscopy . IsCT has a linear alpha-helical structure from Gly3 to Phe13, and {K7}-IsCT has a linear alpha-helical structure from Leu2 to Phe13 . {K7, P8, K11}-IsCT, which has a bend in its middle region, exhibited the highest antibacterial activity without hemolytic activity, suggesting that its proline-induced bend is an important determinant of this selectivity . Tryptophan fluorescence showed that the high selectivity of {K7, P8, K11}-IsCT toward bacterial cells is closely correlated with its highly selective interaction with negatively charged phospholipids . Its potent activity against antibiotic-resistant bacteria suggests that {K7, P8, K11}-IsCT may serve as a promising lead candidate in the development of new peptide antibiotics . Farm Hosp, 2004 Jul-Aug, 28(4), 258 - 65 {Use of MBDS as a tool for the detection of drug-related adverse events}; Corral Baena S et al.; OBJECTIVE: To analyze drug-related adverse events (DRAE) as noted in hospital discharge reports, as well as their severity and drugs involved, and to assess potential avoidability . MATERIAL AND METHODS: A retrospective study for the September-December 2002 period of time in which patients with discharge reports including an ICD-9-CM code E930-E949.9 were selected using the minimum basic data set (MBDS) . RESULTS: DRAEs were detected in 2.15% of all discharge reports, and 229 were retrospectively assessed . In all, 62.45% (n = 143) were DRAEs detected at the Emergency Department, and 37.55% (n = 86) were DRAEs detected during hospitalization . Of these, 57.20% are considered potentially avoidable . Drugs most commonly involved in the outpatient DRAE sample studied included: digoxin (24.47%, avoidable 97.14%) and NSAIDs-opioids (13.98%, avoidable 75%) . Inpatient DRAEs included: anticoagulants (30.23%, avoidable 57.69%) and antimicrobials (17.44%, avoidable 26.67%) . CONCLUSIONS: The study revealed a high proportion of preventable DRAEs around a small number of drugs . Information to prescribing doctors and procedures for treatment follow-up using a unit dose drug dispensing system may be useful to reduce this. Can Vet J, 2004 Aug, 45(8), 695 - 9 Your client credibility: are your pharmacy practices helping or hindering? Ingwersen W. When recommending a specific pharmaceutical, more has to be taken into account than whether the API is indicated for the illness in question . Based on the preceding discussion, product source can have a tremendous impact on efficacy, on therapeutic success, and on practitioners' credibility in the eyes of their clients . However, product source goes beyond simple credibility, encompassing professional ethics and liability . In answering the Ethical question of the month--December 2001 "Should private veterinary practitioners be allowed to produce autogenous vaccines or compound antimicrobial products for use in food producing animals?" Rollin concluded, "one cannot envision a clearer case of unethical behavior." The reality is that quality assurance, efficacy, potency, and safety are not defined for compounded products, and should veterinarians choose to script or dispense one, the responsibility for its quality, efficacy, potency, and safety falls squarely on their shoulders . Ultimately, this also translates into 100% liability should an ADR, illness, or lack of effect, befall the patient . While having access to ELDU and compounded products is crucial in facilitating the treatment of the various diseases that veterinarians face, the regulatory freedom that gives them this choice carries heightened responsibilities when electing this option . In a nutshell, ethical and responsible principles of pharmacy dictate that a veterinarian's first choice should be a veterinary-licensed pharmaceutical for the indication in question . Should this not exist, ELDU of a licensed product with clinically derived therapeutic protocols should be the next choice . Compounded pharmaceuticals should only be used when no licensed (those sporting a DIN) product exists, and extreme cautions should be exercised when using transdermal formulations . Liability dictates that this decision be undertaken with informed consent of the owner and with appropriate due diligence when selecting a compounding service provider . Various articles have been written that provide the veterinarian with guidance when making this decision. Can Vet J, 2004 Aug, 45(8), 661 - 6 Otitis media in dairy calves: a retrospective study of 15 cases (1987 to 2002); Francoz D et al.; Epidemiological data, clinical signs, complementary examination findings, antimicrobial treatments, and outcome were reviewed in 15 calves diagnosed with otitis media at the Centre hospitalier universitaire veterinaire de l'Universite de Montreal between 1987 and 2002 . Age at presentation ranged from 2 to 18 weeks . A purulent ear discharge and epiphora were seen in 8/12 and 6/15 cases, respectively . Neurological signs observed were head tilt (13), eyelid ptosis (7), paresis/paralysis of the pinna (8), ataxia (2), strabismus (2), and convulsions (1) . Concurrent pneumonia was frequently diagnosed (n = 11) . A Mycoplasma sp . was the principal pathogen isolated from ear discharge; 6 out of 6 samples submitted were positive for mycoplasma . Tympanic bullae radiographs were considered abnormal in 12 out of 13 cases . Cerebrospinal fluid analysis was considered abnormal in 2 out of 5 cases . The antibiotic most commonly used was enrofloxacin (n = 7) . Average treatment duration was 19.6 days . Four out of 8 treated animals for which follow-up information was available completely recovered . These results suggest that M . bovis is a major pathogen of otitis media in dairy calves and effective antimicrobial therapy should be of long duration. Aktuelle Urol, 2004 Sep, 35(5), 406 - 12 {Experimental investigations of the optimal therapy of systemic BCG infection in vivo}; Jurczok A et al.; PURPOSE: Hematogenous spread of BCG after intravesical instillation against bladder cancer is rare, but may result in systemic infection and hypersensitivity reaction . We investigated fluoroquinolones and steroids in an animal model to improve the therapeutic options in local and systemic BCG infection . Furthermore, we tested the antitumor effectiveness of intravesical BCG with simultaneous application of fluoroquinolones and/or steroids . METHODS: After systemic BCG infection, experiments were performed with quinolones as antimicrobial agent . Trimethoprim/sulfamethoxazole (TMS) was also tested in comparison to quinolones as a non-specific antimicrobial agent . To evaluate the hyperergic reaction after repeated BCG infection (hypersensitivity model), re-infection was performed seven days after primary infection with accompanying oral antimicrobial therapy with and without steroids . Intravesical tumor therapy was carried out with BCG in orthotopic murine bladder tumor model MB 49 together with simultaneous antimicrobial therapy . RESULTS: After primary infection, quinolones led to a significant prolonged survival independent of steroid administration . Steroids alone after primary BCG infection reduced the survival . In contrast to these experiments, only steroid-treated mice had a significant improvement in survival after a second challenge with BCG . Therapeutic efficacy of BCG was not affected by antibacterial therapy with quinolones . Steroids alone induced a significantly increased death rate during intravesical BCG therapy . CONCLUSION: Quinolones have a positive effect on survival in acute systemic BCG infection in mice . Re-infection with BCG led to severe hyperergic reaction that can only be influenced by steroids . Thus, quinolones can be used in primary systemic BCG infection after topical application as a sufficient alternative to common tuberculostatics . Repeated BCG instillation may lead to hyperergic reaction, making additional administration of steroids essential . In this animal model, therapeutic efficacy of BCG obviously was not affected by additional administration of antimicrobials. J Pharm Pharm Sci, 2004 Jul 16, 7(2), 241 - 51 Multicomposite ultrathin capsules for sustained ocular delivery of ciprofloxacin hydrochloride; Bhadra D et al.; PURPOSE: The present work is intended to develop a sustained bioadhesive drug delivery system for delivery of Ciprofloxacin Hydrochloride in Cul-de-Sac for sustained and effective antimicrobial chemotherapy . For this, ultrathin multicomposite capsular systems were selected . METHODS: Multicomposite ultrathin capsules are molecular assemblies of tailored architecture having layer-by-layer adsorption of oppositely charged macromolecules onto colloidal particles . In the present study colloidal calcium phosphate core and gluateraldehyde fixed RBCs were used as core on which alginate (-vely charged) and polyallylamine hydrochloride (+vely charged) polyelectrolyte coating was deposited alternatively upto 10th layer . The coating in each subsequent layer was determined by changes in zeta potential . Ciprofloxacin hydrochloride was loaded in the capsules by incubation with the capsules suspended in phosphate buffer saline pH 7.4 . The cores of the capsules were then removed by treatment with 0.1N HCl for calcium phosphate core and by sodium hypochlorite for RBC cored capsules . The hollow ciprofloxacin HCl loaded capsules were the evaluated in-vitro for pattern of layer-by-layer drug loading, drug release, stability at various temperatures and ionic concentrations and corneal retention . RESULTS: The core removal process was found to have minimal effects on drug loading in capsules . The drug loading was found to be higher for RBC cored hollow capsules and hence release rate was lower as compared to calcium cored hollow capsules . Draize test for corneal irritancy proved that the capsules were not irritating . The capsules were found to deliver the ciprofloxacin in cul-de-sac of rabbit's eyes for prolonged period . CONCLUSION: Based on corneal retention studies and tear drug concentration, the capsules can be considered for suitable and safe use for sustained ocular delivery of drugs. Mund Kiefer Gesichtschir . 2004 Sep 9; {Epub ahead of print} {Bone collected with a bone collector during dental implant surgeryMicrobiological analysis}; Kuttenberger JJ et al.; BACKGROUND . Simultaneous implantation and augmentation using autogenous bone collected during implant surgery is a well-established procedure in oral implantology . The aims of this study were (1) to identify any bacterial contamination of bone obtained with a bone collector, and (2) to verify the antimicrobial effect of rinsing the bone collector with a 0.1% chlorhexidine solution prior to augmentation . MATERIAL AND METHODS . A total of 39 patients undergoing a simultaneous implantation and augmentation procedure were examined . All patients rinsed their mouths with a 0.1% chlorhexidine solution for 2 min prior to surgery . Bone was collected with the Osseous Coagulum Trap(R), while saliva was collected with a separate suction tip . Once bone collection was complete a microbiological swab was taken from the bone collector (sample 1); before the bone was taken from it 200 ml of a 0.1% chlorhexidine solution was aspirated into the collector, after which the bone was removed and the collector sieve was (sample 2) sent for microbiological analysis which included aerobic and anaerobic cultivation of microorganisms and their identification and semiquantitative assessment of microbial growth . RESULTS . Before the collector was rinsed with chlorhexidine microbial contamination was found in 34 (82.7%) of the 39 samples, and 37 different microbial species were identified in cultures . When the collector had been rinsed with 200 ml 0.1% chlorhexidine a significantly lower rate of microbial contamination was found: 66.7% of the samples were sterile . CONCLUSIONS . Despite separate suction techniques for bone dust and saliva and preoperative use of a chlorhexidine mouthwash, bacterial contamination of bone obtained from the mouth with a bone collector has to be anticipated . Not only the physiological bacteria of the oral flora, but also the microorganisms frequently associated with implant failure can be found . Rinsing the bone collector with 200 ml of a 0.1% chlorhexidine solution significantly reduces microbial contamination . The effects on bone vitality must be studied before routine rinsing with chlorhexidine can be recommended. J Clin Microbiol, 2004 Sep, 42(9), 4083 - 91 Development and validation of a diagnostic DNA microarray to detect quinolone-resistant Escherichia coli among clinical isolates; Yu X et al.; The incidence of resistance against fluoroquinolones among pathogenic bacteria has been increasing in accordance with the worldwide use of this drug . Escherichia coli is one of the most relevant species for quinolone resistance . In this study, a diagnostic microarray for single-base-mutation detection was developed, which can readily identify the most prevalent E . coli genotypes leading to quinolone resistance . Based on genomic sequence analysis using public databases and our own DNA sequencing results, two amino acid positions (83 and 87) on the A subunit of the DNA gyrase, encoded by the gyrA gene, have been identified as mutation hot spots and were selected for DNA microarray detection . Oligonucleotide probes directed against these two positions were designed so that they could cover the most important resistance-causing and silent mutations . The performance of the array was validated with 30 clinical isolates of E . coli from four different hospitals in Germany . The microarray results were confirmed by standard DNA sequencing and were in full agreement with phenotypic antimicrobial susceptibility testing. Int J Antimicrob Agents, 2004 Sep, 24 Suppl 1, S23 - 7 Mycoplasma genitalium urethritis in men; Ishihara S et al.; Mycoplasma genitalium was first isolated from two men with non-gonococcal urethritis (NGU) and thereafter shown to produce urethritis in subhuman primates, inoculated intraurethrally . This mycoplasma has been detected significantly more often in patients with acute NGU, particularly in patients with non-chlamydial NGU, than in subjects without urethritis . The prevalence of M . genitalium-positive non-chlamydial NGU ranges from 18 to 46% of all non-chlamydial NGU cases . In addition, the persistence of M . genitalium in the urethra after antimicrobial chemotherapy is associated with persistence or recurrence of NGU . The various results reported to date tend to support the proposition that M . genitalium is a pathogen of NGU . M . genitalium is highly susceptible to tetracyclines, macrolides, and some new fluoroquinolones, but the clinical data on the chemotherapy in M . genitalium-positive NGU is extremely limited . Because of the possible association between the post-treatment presence of M . genitalium in the urethra and persistent or recurrent NGU, the eradication of this mycoplasma from the urethra is essential in the management of patients with M . genitalium-positive NGU . Further studies are required to establish the optimal chemotherapy for M . genitalium-positive NGU. FEMS Immunol Med Microbiol, 2004 Oct 1, 42(2), 225 - 31 Bacterial products increase expression of the human cathelicidin hCAP-18/LL-37 in cultured human sinus epithelial cells; Nell MJ et al.; The respiratory epithelium plays a major role in the primary defense of the airways against infection . It has been demonstrated that bacterial products are involved in the induction of inflammatory reactions of the upper airways . Little is known about the effects of bacterial products on expression of the antimicrobial peptide hCAP-18/LL-37, the only human cathelicidin identified so far . The aim of this study was to investigate the effects of bacterial products from both gram-positive and gram-negative bacteria on the expression of hCAP-18/LL-37 by sinus epithelial cells using an air-exposed tissue culture model . Lipopolysaccharide and lipoteichoic acid both increased hCAP-18/LL-37 expression in cultured sinus epithelium as assessed by immunohistochemistry, where maximal stimulation occurred at 100 ng ml(-1) lipopolysaccharide or 10 microg ml(-1) lipoteichoic acid . The stimulatory effect of lipopolysaccharide and lipoteichoic acid was not restricted to expression of hCAP-18/LL-37, since also mucin expression and IL-8 release from cultured sinus epithelium cells were increased by lipopolysaccharide and lipoteichoic acid . This suggests that bacterial products may stimulate innate immunity in the upper airways. FEMS Immunol Med Microbiol, 2004 Oct 1, 42(2), 213 - 8 Geographical distribution of antimicrobial resistance among Escherichia coli causing acute uncomplicated pyelonephritis in the United States; Sannes MR et al.; The susceptibility to 12 antimicrobial agents of 165 Escherichia coli isolates from women with acute uncomplicated pyelonephritis of mild to moderate severity was analyzed by geographic region in the US . Ampicillin, trimethoprim, and trimethoprim/sulfamethoxazole resistance exhibited a descending prevalence gradient from west to east . Composite antimicrobial resistance phenotypes also exhibited significant regional differences, with a greater prevalence of most combined resistance profiles seen in the Pacific region of the US, but with significant north-south variation for combined ampicillin/sulfisoxazole resistance . These findings suggest geographical segregation of resistant clones and/or resistance elements among uropathogenic E . coli within the US, which is relevant both to clinical practice and to understanding the basis for the current epidemic of antimicrobial resistance in E . coli. Eur Urol, 2004 Oct, 46(4), 522 - 4; discussion 524-5 Management of acute epididymitis: are European guidelines being followed? Drury NE, Dyer JP, Breitenfeldt N, Adamson AS, Harrison GS. OBJECTIVE: Acute epididymitis is increasing in men aged 35 years or under due to sexually-transmitted Chlamydia trachomatis . This study examines whether Urological surgeons are following European guidelines for the management of acute epididymitis in these patients . METHODS: A postal questionnaire survey was conducted of specialists in Urology in two regions of the UK . RESULTS: Of 79 completed replies, 41 (52%) take a detailed sexual history but only 34 (43%) refer patients to a Genitourinary medicine clinic . Quinolones are the most commonly prescribed first-line antibiotic by 56 (71%) respondents, principally ciprofloxacin . CONCLUSIONS: The current management of acute epididymitis in young men must be improved . Ciprofloxacin is not the optimal antimicrobial for the treatment of urogenital chlamydial infection . We recommend that all such patients be referred to local Genitourinary medicine services for contact-tracing and treatment of their sexual partners. Vet Surg, 2004 Sep-Oct, 33(5), 542 - 50 A prospective study of postoperative surgical site infections in dogs and cats; Eugster S et al.; OBJECTIVE: To assess postoperative surgical site infection (SSI) rate and to identify associated predictive factors . STUDY DESIGN: Prospective clinical study . ANIMALS: Dogs and cats that had surgery (1010 interventions) during 58 weeks from April 1999 to June 2000 . METHODS: Data sheets were completed by clinicians . Patients were controlled for clinical evidence of SSI at suture removal . Two definitions of SSI ("infection" and "infection/inflammation") were developed specifically for this study and used for statistical analysis . Logistic regression models were built in order to identify significant predictive factors for SSI . RESULTS: Wounds with "infection/inflammation" occurred in 5.8% and "infected" wounds in 3% of patients . The outcome "infection" was associated with 3 major risk factors (duration of surgery, increasing number of persons in the operating room, dirty surgical site) and 1 protective factor (antimicrobial prophylaxis) . The outcome "infection/inflammation" was associated with 6 significant factors (duration of anesthesia, duration of postoperative intensive care unit stay, wound drainage, increasing patient weight, dirty surgical site, and antimicrobial prophylaxis) . CONCLUSIONS: SSI frequency in companion animals is comparable with the frequency observed in human surgical patients . Several significant predictive factors for SSI in small animals surgery were identified . CLINICAL RELEVANCE: Baseline information for SSI surveillance in our hospital and for comparison with other studies was defined . The factors identified may help to predict infections in surgical patients and to take adequate preventive measures for patients at risk. Folia Med (Plovdiv), 2004, 46(1), 5 - 8 Rational basis for optimizing antibiotic dosing regimens; Soriano F et al.; Adjustment of the antibiotic dosage is usually done taking into account pharmacokinetic parameters . However, as the bacterial response to the antimicrobial effect varies it is important to correlate pharmacokinetics with antimicrobial susceptibility data, the latter measured by determining the Minimum Inhibitory Concentration (MIC) . It is now widely accepted that the ratio between the maximum antibiotic concentration achieved in serum and the MIC of the pathogen correlates with efficacy of aminoglycosides and fluoroquinolones . The ratio between the area under the serum concentration-time curve and the MIC correlates with efficacy of aminoglycosides and fluoroquinolones but also of vancomycin, tetracyclines, azithromycin, and quinupristin/dalfopristin . Finally the time for which antibiotic concentration in serum remains above the MIC correlates with efficacy of beta-lactams, most macrolides, and clindamycin . All the above mentioned pharmacodynamic parameters should be considered for optimizing antibiotic dosage. Pharmacoepidemiol Drug Saf, 2004 Sep, 13(9), 653 - 7 Utilization of parenteral anti-infective agents in the medical emergency unit of a tertiary care hospital: an observational study; Gupta M et al.; A pharmacy based prescription audit was undertaken in the medical emergency unit of a tertiary care hospital to determine the frequency of prescribing of parenteral anti-infective agents . During the study period, 885 patients were screened . The analysis was done for the number of parenteral anti-microbials in each prescription frequency of individual drug prescribe number and dose unit (DDD), frequency of age and sex, site of infection and daily cost incurred by the patient . It was found that 400 patients (45.2%) received parenteral anti-infective agents . Cephalosporins, aminoglycosides and metronidazole accounted for about 70% of total antimicrobial use . More than 50% of patients had culture sensitivity reports available . The mean (standard deviation, SD) daily cost of antibiotic was USD 3.8 (7.7), median; range 2 (0.1-85.7) . Two anti-microbials per prescription were indicated in most of the patients (43.88) . In conclusion we have provided an overview of parenteral anti-infective use in medical emergency, which may serve as a basis for intervention and improvement in prescribing pattern of parenteral anti-microbials. Nat Struct Mol Biol, 2004 Oct, 11(10), 963 - 7 Epub 2004 Sep 12. The nisin-lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics; Hsu ST et al.; The emerging antibiotics-resistance problem has underlined the urgent need for novel antimicrobial agents . Lantibiotics (lanthionine-containing antibiotics) are promising candidates to alleviate this problem . Nisin, a member of this family, has a unique pore-forming activity against bacteria . It binds to lipid II, the essential precursor of cell wall synthesis . As a result, the membrane permeabilization activity of nisin is increased by three orders of magnitude . Here we report the solution structure of the complex of nisin and lipid II . The structure shows a novel lipid II-binding motif in which the pyrophosphate moiety of lipid II is primarily coordinated by the N-terminal backbone amides of nisin via intermolecular hydrogen bonds . This cage structure provides a rationale for the conservation of the lanthionine rings among several lipid II-binding lantibiotics . The structure of the pyrophosphate cage offers a template for structure-based design of novel antibiotics. J Biol Chem, 2004 Nov 19, 279(47), 48751 - 9 Epub 2004 Sep 10. Rodent and human mast cells produce functionally significant intracellular reactive oxygen species but not nitric oxide; Swindle EJ et al.; In immunity, reactive oxygen species (ROS) and nitric oxide (NO) are important antimicrobial agents and regulators of cell signaling and activation pathways . However, the cellular sources of ROS and NO are much debated . Particularly, there is contention over whether mast cells, key secretory cells in allergy and immunity, can generate these chemical species, and if so, whether they are of functional significance . We therefore examined directly by flow cytometry the capacity of mast cells to generate intracellular ROS and NO using the respective cell-permeable fluorescent probes dichlorodihydrofluorescein and diaminofluorescein and evaluated the effects of inhibitors of ROS and NO synthesis on cell degranulation . For each of three mast cell types (rat peritoneal mast cells, mouse bone marrow-derived mast cells, and human blood-derived mast cells), degranulation stimulated by IgE/antigen was accompanied by production of intracellular ROS but not NO . Inhibition of ROS production led to reduced degranulation, indicating a facilitatory role for ROS, whereas NO synthase inhibitors were without effect . Likewise, bacterial lipopolysaccharide and interferon-gamma over a wide range of conditions failed to generate intracellular NO in mast cells, whereas these agents readily induced intracellular NO in macrophages . NO synthase protein, as assessed by Western blotting, was readily induced in macrophages but not mast cells . We conclude that rodent and human mast cells generate intracellular ROS but not NO and that intracellular ROS but not intracellular NO are functionally linked to mast cell degranulation. Curr Pain Headache Rep, 2004 Oct, 8(5), 364 - 8 Fibromyalgia: the gastrointestinal link; Wallace DJ et al.; Patients with fibromyalgia (FM) frequently have gastrointestinal symptoms and signs . This article critically reviews the available literature and concludes the following: evidence that inflammatory bowel disease is associated with FM is contradictory, but should be looked for in patients taking concomitant steroids; patients diagnosed with celiac disease often have a history of FM or irritable bowel syndrome (IBS) that may or may not be present; reflux, nonulcer dyspepsia, and noncardiac chest pain are common in FM patients; medications used to manage pain, inflammation, and gastrointestinal complaints confound the management of FM; and IBS affects smooth muscles and the parasympathetic nervous system, while FM patients have complaints of striated muscles and dysfunction of the sympathetic nervous system . Of those patients with FM, 30% to 70% have concurrent IBS . Small intestinal bacterial overgrowth is associated with hyperalgesia and IBS-like complaints, is common in FM, and responds transiently to antimicrobial therapy. J Negat Results Biomed . 2004 Sep 10;3(1):2. Fusion of green fluorescent protein to the C-terminus of granulysin alters its intracellular localization in comparison to the native molecule; Hanson DA et al.; The engineering of green fluorescent protein (GFP) fusion constructs in order to visibly tag a protein of interest has become a commonly used cell biology technique . Although caveats to this approach are obvious, literature reports in which the chimeric molecule behaves differently than the native molecule are scant . This brief report describes one such case . Granulysin, a small lytic and antimicrobial protein produced by cytotoxic lymphocytes, traffics to the regulated secretory system and is subsequently released from cells upon proper stimulus . In an attempt to elucidate mechanisms by which it accumulates in and is released from cytolytic granules, GFP was fused to the C-terminus of granulysin and expressed in an NK cell line . A control construct expressing the native protein was similarly expressed . The data demonstrate that, while the fusion protein is expressed and secreted, its subcellular localization is altered in comparison to native granulysin . Thus, the addition of GFP to the C-terminus of granulysin obscures the signal(s) that cytotoxic lymphocytes use to sort it to the regulated secretory pathway despite its normal biosynthesis and secretion . This example is offered as a cautionary account for other researchers who contemplate using this technology. Medinfo . 2004;2004(CD):1677. CustomID: A Highly Customizable Infectious Diseases Management Tool for Providing Institution-specific Decision Support on the Web and PDA; Kawamoto K et al.; Optimal infectious diseases (ID) management requires consideration of multiple institution-specific factors, such as local antimicrobial resistance profiles, formulary constraints, and ward-specific isolation procedures . At the same time, available electronic ID management guides do not take such institution-specific factors into consideration . Given this need, we developed CustomID(c), an ID management tool that supports rapid dissemination of institution-specific content on Web, Palm, and Pocket PC platforms . In this poster, we describe the design and development of CustomID, as well as an initial evaluation study that demonstrated our tool's ability to effectively provide institution-specific decision support. Leuk Lymphoma, 2004 Jun, 45(6), 1293 - 6 Lethal pulmonary hemorrhage caused by a fulminant Stenotrophomonas maltophilia respiratory infection in an acute myeloid leukemia patient; Rousseau A et al.; Stenotrophomonas maltophilia (Sm) pneumonia in immunocompromized hosts is an increasingly common nosocomial infection . Even though resistant to multiple antimicrobials, this gram-negative bacteria usually does not present with a fulminant course leading to a fatal hemorrhagic respiratory infection in neutropenic patients . We report here the case of a 63-year-old woman treated by intensive chemotherapy for acute myeloid leukemia (AML) who presented while severely neutropenic and thrombocytopenic a Sm pulmonary infection with hemoptysis leading to death in 48 h . The bronchoalveolar lavage (BAL) performed shortly before death was highly hemorrhagic and contained a striking amount of extra- and intra-cellular pathogens . Blood and BAL cultures grew S . maltophilia . Post-mortem examination revealed bilateral extensive intra-alveolar hemorrhage (IAH) associated with a great amount of microorganisms and severe bone marrow aplasia was observed without evidence of leukemia residual disease . Sm pneumonia usually does not evolve into such a devastating clinical picture although infections due to the bacteria are known to be associated with high morbidity and mortality . So far, the present observation is the fourth similar case reported in the literature . Even though an early diagnosis and an adequate antibiotic prescription may improve Sm infection prognosis, S . maltophilia proves difficult to eradicate due to a high resistance rate in part intrinsic but also in part acquired. FEMS Microbiol Lett, 2004 Sep 15, 238(2), 315 - 20 The targeted inactivation of polyketide synthase mycAV in the mycinamicin producer, Micromonospora griseorubida, and a complementation study; Anzai Y et al.; Mycinamicin is a 16-membered macrolide antibiotic produced by Micromonospora griseorubida A11725, which shows strong antimicrobial activity against gram-positive bacteria . Recently, the nucleotide sequences of the mycinamicn biosynthetic gene cluster in M . griseorubida have been completely determined . Mycinamicin non-producer M7A21 was isolated by mycAV inactivation, which encodes the module 7 of mycinamicin polyketide synthase (PKS) required for the biosynthesis of the mycinamicin biosynthetic intermediate protomycinolide-IV (PML-IV) . When the bioconversion to mycinamicin II (M-II) from PML-IV was performed using M7A21 and the feeding culture method, the productivity of M-II was the same as that of M-II in wild-type strain A11725 . p446M7 containing mycAV was constructed using the Escherichia coli-Streptomyces shuttle vector pGM446 . The mycinamicin productivity of M7A21 was restored by the introduction of p446M7 into the M7A21 cell, but almost all p446M7 was integrated into the chromosome of M7A21 because the plasmid was unstable in M7A21 . The feeding culture and the introduction of the complement gene for M7A21 would be powerful tools to perform combinatorial biosynthesis for the production of new macrolide antibiotics. J Appl Microbiol, 2004, 97(4), 861 - 6 The incidence of Shiga toxin-producing Escherichia coli in cattle with mastitis in Brazil; Lira WM et al.; AIMS: To determine the prevalence and molecular characteristics of Shiga toxin-producing Escherichia coli (STEC) isolates from bovine mastitic milk in Brazil . METHODS AND RESULTS: A total of 2144 milk samples from dairy cattle showing mastitis were screened for the presence of E . coli . A total of 182 E . coli isolates were selected and examined . All were subjected to dot blot analysis using the CVD419 probe for the detection of the enterohaemolysin (hly) gene, and to a multiplex PCR for the detection of stx1, stx2 and eaeA genes . STEC were isolated from 22 (12.08%) milk samples . All the STEC isolates were tested for sensibility to 10 antimicrobials; the resistances most commonly observed were to cephalothin (86.3%), tetracycline (63.6%) and doxycycline (63.6%) . CONCLUSION: STEC isolates were found in bovine mastitic milk in Brazil . SIGNIFICANCE AND IMPACT OF THE STUDY: STEC isolates from mastitic milk were potentially pathogenic for human in that they belonged to serogroups associated with diarrhoea and haemolytic-uraemic syndrome, some of them were stx2, eaeA and hly positive. J Pept Res, 2004 Oct, 64(4), 151 - 8 Role of C-terminal heptapeptide in pore-forming activity of antimicrobial agent, gaegurin 4; Kim HJ et al.; Gaegurin 4 (GGN4) is an antimicrobial peptide of 37 amino acids isolated from the skin of a frog, Rana rugosa . GGN4 has a disulfide bond between the residues 31 and 37, which is highly conserved among the antimicrobial peptides isolated from skin of the genus, Rana . However, the role of this C-terminal heptapeptide motif is not well understood . In this work, we compared the membrane effects of the full-length GGN4 (C37) and GGN4 1-30 (C30), which is devoid of the C-terminal seven amino acids to elucidate the function of the C-terminal motif . C37 induced significantly larger membrane conductance (>10x) in the model lipid bilayers formed with acidic and neutral phospholipids and larger K+ efflux from gram-positive (>30x) and gram-negative bacteria . However, the pores induced by C37 and C30 were not different in their permeability to K+ over Cl- (permeability ratio of K+ to Cl- = 4.8-7.1) . In addition, the pore-forming effect of C37 or C30 in acidic membranes was not different from that in neutral membranes . Furthermore, C37-induced K+ efflux was not significantly decreased by the reducing agent, dithiothreitol . The results indicate that C-terminal heptapeptide sequence plays an important role in maintaining the high pore-forming activity of GGN4, but does not participate in forming GGN4-induced pore structure . The disulfide bond in this region does not appear critical for such high ionophoric activity of GGN4. Clin Infect Dis, 2004 Aug 15, 39(4), 474 - 80 Epub 2004 Jul 22. Indicators of potentially drug-resistant bacteria in severe nursing home-acquired pneumonia; El Solh AA et al.; BACKGROUND: Knowledge of the determinant factors responsible for the presence of antimicrobial-resistant pathogens in severe nursing home-acquired pneumonia (NHAP) is deemed essential for antibiotic selection . METHODS: Data for institutionalized patients with cases of severe pneumonia confirmed by culture of protected bronchoalveolar lavage fluid samples (> or =10(3) cfu/mL) during a 36-month period were analyzed . A classification tree with a sensitivity of 100% was developed using binary recursive partitioning to predict which patients are unlikely to have drug-resistant pathogen (DRP)-related pneumonia . RESULTS: Of the 88 patients who satisfied the inclusion criteria, 17 had at least 1 DRP recovered from the lower respiratory tract . The predictor variables were the Activity of Daily Living score and previous use of antibiotics . Prospective application of the model in 47 patients over a 24-month period yielded a sensitivity of 100% (95% confidence interval {CI}, 71.3%-100%) and a specificity of 69.4% (95% CI, 51.9%-83.6%) . CONCLUSIONS: The use of the tree may provide a more rational basis for selecting initial therapy for severe NHAP after it is validated in a large prospective study. Clin Infect Dis, 2004 Aug 15, 39(4), 468 - 71 Epub 2004 Jul 30. The role of diet in the treatment of travelers' diarrhea: a pilot study; Huang DB et al.; A pilot study was performed to compare the effects of a restricted physiologic diet in 48 subjects with those of an unrestricted diet in 57 subjects on the duration and symptoms of acute travelers' diarrhea among US adults being treated with an antimicrobial agent in Mexico . Restricted physiologic diet was defined as the avoidance of certain foods during diarrheal illness, as specified in limited published literature . The mean duration of diarrhea (37 vs . 33 h) and clinical symptoms were similar between those practicing the restricted diet and those practicing unrestricted diets . These results suggest that restricting diet during treatment of travelers' diarrhea with an antimicrobial agent is not associated with improvement of clinical symptoms or with decreased duration of diarrhea . However, a much higher number of subjects would need to be studied to prove this point statistically. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2004 Sep, 98(3), 267 - 73 Tuberculosis: medical management update; Yepes JF et al.; Tuberculosis (TB) is an infectious chronic disease . After decades of steadily declining prevalence, the disease has reemerged in the last 5 years . Symptoms of TB are mild and not specific and can be classified as either systemic or localized to target organs . Microscopic examination of the sputum remains an inexpensive and rapid way to identify highly infectious patients . Four different antimicrobial agents-rifampin, ethambutol, pirazinamide, and isoniazid-form the basis of currently recommended antituberculosis therapy . Tuberculosis could be an occupational risk for health care workers . Dentists must be involved in the health promotion and early detection of TB. Ostomy Wound Manage, 2004 Aug, 50(8), 48 - 62 Impact of antimicrobial gauze on bacterial colonies in wounds that require packing; Motta GJ et al.; Heavy microbial contamination has been associated with delayed wound healing and infection in both acute and chronic wounds . A prospective, randomized, 5-week controlled, open label, multicenter study was conducted to determine whether using antimicrobial gauze containing polyhexamethylene biguanide in wounds that require packing will result in a greater reduction of bacterial colony counts than using a gauze without polyhexamethylene biguanide (the control) . Twenty-one subjects were randomized to the treatment or control dressing . Wounds were evenly distributed with respect to etiology and both study groups had a median baseline wound size of 7 cm2 . At baseline, 15 microbial isolates were recovered and counted in treatment group wounds and 12 were recovered in the controls . At Week 1, six isolates were recovered from subjects in the polyhexamethylene biguanide antimicrobial gauze treatment group while 10 were recovered in the control . Change in polymicrobial bioburden was most prominent during the first few weeks of the study in the polyhexamethylene biguanide group . Polymicrobial counts in the treatment group remained reduced for the following three study weeks, returning to baseline at Week 4 . In the control group, the number of polymicrobial cultures rose to 60% above baseline at Week 4 . Two wounds of subjects randomized to the polyhexamethylene biguanide antimicrobial gauze healed; one wound in the control group healed . Polyhexamethylene biguanide antimicrobial gauze dressing could be an important adjunct to control the polymicrobial bioburden of delayed closure surgical wounds, pressure ulcers, and diabetic foot ulcers . Additional studies seem warranted. Ostomy Wound Manage, 2004 Aug, 50(8), 28 - 41 A comparison of an antimicrobial wound cleanser to normal saline in reduction of bioburden and its effect on wound healing; Lindfors J; Microbial bioburden in both acute and chronic wounds is an important factor in wound healing . Consequently, the reduction of bioburden to host-manageable levels, as well as the elimination of certain virulent forms of wound pathogens (regardless of their number), has become a goal of the wound care professional . A prospective, controlled clinical study using accepted sampling methods was conducted to compare the use of an antimicrobial wound cleanser (0.057% sodium hypochlorite in an isotonic saline solution) to normal saline on the reduction of bioburden and wound size . During the 2-month study, 100% of the wounds cleansed with the antimicrobial wound cleanser (n = 9) demonstrated aerobic bioburden reduction from baseline in a range from 1 to 4 logs per wound, while 56% of the wounds cleansed with normal saline (n = 9) showed an increase in aerobic bioburden levels . The proportion of wounds exhibiting a reduction in wound size was higher in the antimicrobial wound cleanser group than in the saline group . Further research to increase understanding of the relationship between wound bioburden, healing, and cleansing agents is needed. N Engl J Med, 2004 Sep 9, 351(11), 1089 - 96 Oral erythromycin and the risk of sudden death from cardiac causes; Ray WA et al.; BACKGROUND: Oral erythromycin prolongs cardiac repolarization and is associated with case reports of torsades de pointes . Because erythromycin is extensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, thereby increasing the risk of ventricular arrhythmias and sudden death . We studied the association between the use of erythromycin and the risk of sudden death from cardiac causes and whether this risk was increased with the concurrent use of strong inhibitors of CYP3A . METHODS: We studied a previously identified Tennessee Medicaid cohort that included 1,249,943 person-years of follow-up and 1476 cases of confirmed sudden death from cardiac causes . The CYP3A inhibitors used in the study were nitroimidazole antifungal agents, diltiazem, verapamil, and troleandomycin; each doubles, at least, the area under the time-concentration curve for a CYP3A substrate . Amoxicillin, an antimicrobial agent with similar indications but which does not prolong cardiac repolarization, and former use of erythromycin also were studied, to assess possible confounding by indication . RESULTS: The multivariate adjusted rate of sudden death from cardiac causes among patients currently using erythromycin was twice as high (incidence-rate ratio, 2.01; 95 percent confidence interval, 1.08 to 3.75; P=0.03) as that among those who had not used any of the study antibiotic medications . There was no significant increase in the risk of sudden death among former users of erythromycin (incidence-rate ratio, 0.89; 95 percent confidence interval, 0.72 to 1.09; P=0.26) or among those who were currently using amoxicillin (incidence-rate ratio, 1.18; 95 percent confidence interval, 0.59 to 2.36; P=0.65) . The adjusted rate of sudden death from cardiac causes was five times as high (incidence-rate ratio, 5.35; 95 percent confidence interval, 1.72 to 16.64; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medications . In contrast, there was no increase in the risk of sudden death among those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the study antibiotic medications who had formerly used CYP3A inhibitors . CONCLUSIONS: The concurrent use of erythromycin and strong inhibitors of CYP3A should be avoided . Aust Vet J, 2004 Jul, 82(7), 413 - 6 Hypokalaemia as a cause of recumbency in an adult dairy cow; Johns IC et al.; A 3-year-old Holstein cow was presented for evaluation of recumbency . Physical examination and laboratory evaluations resulted in a diagnosis of hypokalaemia causing extreme skeletal muscle weakness . Treatment involved intravenous and oral potassium supplementation, antimicrobial and anti-inflammatory therapy, and management of recumbency using a flotation tank (the Aquacow Rise System) . The cow recovered and returned to the milking herd . Multifactorial elements were identified as the cause of hypokalaemia including inappetance, treatments for ketosis and administration of dexamethasone. J Thorac Cardiovasc Surg, 2004 Sep, 128(3), 480 - 6 Primary closure for postoperative mediastinitis in children; Ohye RG et al.; OBJECTIVES: Mediastinitis affects approximately 1% of children undergoing median sternotomy . Conventional therapy involves debridement followed by open wound care with delayed closure, days to weeks of closed suction or antimicrobial irrigation, and vacuum-assisted closure or muscle flap closure . We hypothesized that primary closure without prolonged suction or irrigation is an effective, less traumatic treatment for mediastinitis in children . METHODS: From January 1986 to July 2002, 6705 procedures involving median sternotomy were performed at the C . S . Mott Children's Hospital, resulting in 57 cases of mediastinitis (0.85%) . Cases were divided into 2 groups, with 42 cases treated with primary closure and 15 cases treated with delayed or muscle flap closure . The 42 cases of primary closure comprised the primary study group of this institutional review board-approved, retrospective analysis . Patient demographics, surgical variables, mediastinitis-related parameters, and outcomes were evaluated . RESULTS: One patient had recurrent mediastinitis for an overall infection eradication rate of 97% (40/41) . Three patients (7%) required re-exploration for suspected ongoing infection . Of these re-explorations, 1 patient had evidence of continued mediastinitis . The remaining 2 patients with sepsis of unclear cause had no clinical or culture evidence of recurrent infection . One of these patients ultimately died of sepsis without active mediastinitis for a hospital survival of 97% (41/42) . No significant differences could be detected between the treatment successes and failures in this small cohort of patients . CONCLUSIONS: Simple primary closure is an effective means to treat selected cases of postoperative mediastinitis in children . The results compare favorably with other more lengthy or debilitating treatments. J Vet Med Sci, 2004 Aug, 66(8), 899 - 903 Effect of antimicrobial agents on the production and release of shiga toxin by enterotoxaemic Escherichia coli isolates from pigs; Uemura R et al.; Edema disease (ED) of pigs is an enterotoxaemic disease caused by enterotoxaemic Escherichia coli (ETEEC) infection . Antimicrobial therapy for pigs with ED is controversial because it may induce death of sickish piglets . In this study, we investigated the effects in vitro of 7 antimicrobial agents, ampicillin, gentamicin, colistin, bicozamycin, fosfomycin, sulfamethoxazole-trimethoprim and enrofloxacin, on the release and production of shiga toxin (Stx) 2e by ETEEC strains . We found that more Stx 2e accumulated in the bacterial cells than was released into supernatant . Associated with inhibition of cell wall synthesis, the exposure to ampicillin or fosfomycin increased the release of Stx 2e . The production levels of Stx 2e in all antimicrobial-treated cultures were equal to the level in the control or less than in the control . These results suggest that cell wall synthesis inhibitors, such as ampicillin and fosfomycin, may change for the worse in the signs in ETEEC infectious pigs . On the other hand, gentamicin, colistin, bicozamycin and enrofloxacin may be useful for the treatment of pigs with ED. Ann Pharmacother, 2004 Oct, 38(10), 1664 - 74 Epub 2004 Sep 07. Atazanavir; Orrick JJ et al.; OBJECTIVE: To review the pharmacology, virology, pharmacokinetics, resistance profile, clinical efficacy, safety, and drug interactions of atazanavir . DATA SOURCES: A PubMed and NLMGateway search (1966-June 2004) utilizing the key words atazanavir and BMS-232632 was performed . Abstracts from scientific meetings, including the Conference on Retroviruses and Opportunistic Infections, International AIDS Society Conference on HIV Pathogenesis and Treatment, Interscience Conference on Antimicrobial Agents and Chemotherapy, and the Infectious Diseases Society of America, were also reviewed . STUDY SELECTION AND DATA EXTRACTION: All publications and meeting abstracts were reviewed, and information relevant to the formulary decision-making process was selected . DATA SYNTHESIS: Atazanavir is a once-daily protease inhibitor (PI) that received approval by the Food and Drug Administration in June 2003 . In clinical trials in antiretroviral (ARV)-naive patients, atazanavir had efficacy similar to that of efavirenz or nelfinavir . In ARV-experienced patients, atazanavir was inferior to lopinavir/ritonavir unless atazanavir was coadministered with low-dose ritonavir . Following failure of an atazanavir-containing regimen in ARV-naive patients, a unique 150L mutation was seen . Atazanavir resistance is likely when resistance to >/=3 PIs is present . Atazanavir can cause increases in unconjugated bilirubin levels, which rarely leads to jaundice or scleral icterus . In contrast to comparators, atazanavir did not negatively impact the lipid profile . Similar to other PIs, atazanavir is metabolized by and inhibits CYP3A at clinically relevant concentrations; therefore, many potential drug interactions exist . CONCLUSIONS: Atazanavir is a once-daily PI that, unlike other PIs, does not negatively impact the lipid profile . Atazanavir may be particularly desirable in patients with hyperlipidemia or other coronary artery disease risk factors. Aliment Pharmacol Ther, 2004 Sep 15, 20(6), 675 - 81 Effect of cyclo-oxygenase inhibitors on Helicobacter pylori susceptibility to metronidazole and clarithromycin; Gu Q et al.; BACKGROUND: We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole . AIM: To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H . pylori . METHODS: Three H . pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometacin for 24 and 48 h . Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively . RESULTS: SC-236 and indometacin inhibited H . pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively . The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control) . Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control) . Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025) . MICs of metronidazole and clarithromycin against H . pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001) . CONCLUSION: Both SC-236 and indometacin suppressed the growth and urease activity of H . pylori in a dose-dependent manner, and increased its susceptibility to the antibiotics. Anal Biochem, 2004 Oct 1, 333(1), 39 - 48 Development and validation of a time-resolved fluorometric immunoassay for screening of antichlamydial activity using a genus-specific europium-conjugated antibody; Tammela P et al.; The lack of high-throughput assays has limited the screening of new antimicrobials against obligate intracellular bacteria, including chlamydia, which cause a variety of diseases . In this study, a novel technological approach was developed to detect intracellular bacteria using time-resolved fluorometric immunoassay (TR-FIA), and the method was validated for susceptibility testing of Chlamydia pneumoniae . In this cell-based, 96-well plate assay, chlamydial inclusions are labeled with europium-conjugated antibody and quantified as time-resolved fluorometric signals by means of a multilabel counter . To confirm the reliability of the TR-FIA, susceptibilities of C . pneumoniae reference strain Kajaani 7 to a set of antimicrobial agents were determined by the TR-FIA, conventional immunofluorescence staining, and real-time polymerase chain reaction . Minimum inhibitory concentrations measured using the different methods demonstrated good to excellent correlation . Data relating to reproducibility (day-to-day variation 9.0%), as well as to the signal-to-background, signal-to-noise, and Z' values (6.5, 6.9, and 0.4, respectively), showed the suitability of the TR-FIA for screening . By means of dual labeling with sulfornodamine B the cytotoxicity of test compounds could be detected simultaneously with the susceptibility testing . In summary, the TR-FIA is a convenient, reliable, and objective alternative for detecting chlamydia in vitro . By being considerably less labor intensive and offering significantly higher throughput, the TR-FIA is especially suitable for screening of new antichlamydial compounds. Fitoterapia, 2004 Sep, 75(6), 577 - 80 Antimicrobial activity and cytotoxicity of Cirsium tenoreanum; Loizzo MR et al.; The methanol and ethyl acetate extracts of the aerial parts of Cirsium tenoreanum, have been evaluated for their phytochemical constituents and antibacterial and cytotoxic properties . Three flavonoids, apigenin, quercetin-3-O-galactoside and kaempferol-3-O-ramnoside, were isolated . The ethyl acetate extract showed a good antiproliferative activity. Spectrochim Acta A Mol Biomol Spectrosc, 2004 Oct, 60(12), 2861 - 73 Co(II), Ce(III) and UO2VI) bis-salicylatothiosemicarbazide complexes: binary and ternary complexes, thermal studies and antimicrobial activity; El-Wahab ZH et al.; A series of new metal complexes of Co(II), Ce(III) and UO(2)(VI), with the Schiff base ligand, H2L, bis-salicylatothiosemicarbazide have been prepared in presence of different molar ratios of LiOH.H2O as a deprotonating agent . Also, the ternary complexes were prepared by using 2-aminopyridine (2-Ampy) or oxalic acid (Ox) as a secondary ligand . All synthesized compounds were identified and confirmed by elemental analyses, molar conductivities, spectral (UV-Vis, IR, 1H NMR, mass) and magnetic moment measurements as well as TG-DSC technique . The changes in the selected vibrational absorption bands in IR and NMR spectra of the Schiff base ligand upon coordination indicate that, the ligand beh