Clin Ter, 2004 Jul-Aug, 155(7-8), 293 - 303 {Community acquired pneumonia of hospitalised patient in the ordinary ward}; Scala R; Despite the evolution of the respiratory diagnostic methods and of the microbiological techniques and despite the introduction of new and effective antimicrobial drugs, community-acquired pneumonia (CAP) still remains a common and potentially lethal disease, as it represents the sixth general cause of death and the first cause of death concerning the infective diseases . The prolonged survival of patients affected by chronic respiratory and non-respiratory disorders and the worrying problem of antibacterial resistance showed by several pathogen agents constitute the possible causes of the epidemiological importance of CAP which still carries on significantly affecting health costs . In this review the author describes the epidemiological, etiological, microbiological, diagnostic and therapeutic aspects of CAP which requires hospitalisation in a non-intensive care setting. Nippon Rinsho, 2004 Nov, 62(11), 2065 - 73 {Efficacy of selective digestive decontamination (SDD) for severe acute pancreatitis}; Kitamura N et al.; Bacterial translocation (BT) is involved in the development of pancreatic infection in severe acute pancreatitis (SAP) and influences the prognosis . We should suppress BT to prevent pancreatic infection and improve survival rate . Selective digestive decontamination (SDD) is rational treatment . We should aim at effective SDD, ensuring the following 4 points: (1) enteral antimicrobials, in combination with, (2) parenteral antibiotics given immediately on admission, (3) hand hygiene, (4) surveillance cultures of throat and rectum . Starting enteral feeding as soon as possible and avoiding long-term SDD is useful for maintaining the defenses of the intestinal mucosa and preventing emergence of resistant bacteria . We used glutamine and dietary fiber besides SDD and were able to reduce pancreatic infection. Clin Orthop, 2004 Oct, (427), 18 - 21 Porcine small intestine submucosa does not show antimicrobial properties; Holtom PD et al.; The goal of this study is to examine whether porcine small intestine submucosa (SIS) exhibits antimicrobial properties in a standard in vitro system, without pretreatment with acetic acid or extraction of soluble proteins . Previous animal studies suggest that porcine SIS may have inherent antibiotic properties . Using the guidelines for disk diffusion susceptibility testing by Bauer, 17/64-inch diameter disks made of porcine small intestine submucosa and of gortex were compared with standard antibiotic-impregnated disks against six organisms . The zone of inhibition was measured after 24 hours and minimum bacterial concentrations were determined by serial dilutions of a solution in which porcine small intestine submucosa was allowed to elute for 24 hours . Neither porcine SIS or gortex discs caused inhibition of the growth of any organism . The porcine small intestine submucosa discs showed bacterial growth on top of the discs whereas the gortex did not . Neither the dilutional concentrations of the porcine small intestine submucosa eluent nor the gortex eluent inhibited the growth of any organism . These findings suggest that the porcine small intestine submucosa does not have intrinsic antimicrobial properties . The growth of bacteria on top of the porcine small intestine submucosa suggests that porcine small intestine submucosa itself may provide a favorable environment for the growth of bacteria . More research is necessary to decide what role porcine small intestine submucosa plays in the treatment of infected surgical sites. Nurs Stand, 2004 Oct 27-Nov 2, 19(7), 56 - 60 The use of silver-based dressings in wound care; Dowsett C; Chronic wounds such as leg ulcers and pressure ulcers are often slow to heal . One of the causes of delayed wound healing is the presence of micro-organisms in the wound . A strategy for the prevention and treatment of wound colonisation or infection, which is receiving renewed attention, is the use of silver-based dressings . Silver has been used as an antimicrobial agent for centuries . It is effective against a broad range of bacteria (including methicillin and vancomycin-resistant strains), yeast, fungi and viruses . A number of new silver-based dressings, some of which act by the sustained release of silver ions to the wound bed, have recently become available, but there are wide variations in the amount of data supporting the use of individual products . This article reviews the evidence base for silver-containing dressings to help practitioners select the most appropriate product for the type of wound being treated. Biomedica, 2004 Sep, 24(3), 262 - 72 {Expression and activity of polymorphisms in the 67-kDa protein of the NADPH oxidase system}; Arias AA et al.; The NADPH oxidase system plays a central role in the antimicrobial activity of phagocytes . This system is initiated by the translocation of cytosolic proteins p67phox, p47phox and p40phox to be in close contact with membrane flavocytochrome b558 . This event begins the electron transfer from cytosolic NADPH to molecular oxygen to produce superoxide anions . Herein, a functional analysis is presented of p67phox polymorphisms identified from healthy humans . Mutations were generated in the p67phox cDNA by site-directed mutagenesis and then transiently expressed in COS7 cells that also expressed gp91phox, p22phox, and p47phox from stable transgenes . The changes Va1166lle, Pro329Ser and His389Gln correspond to possible polymorphisms identified in healthy individuals revealed a functional activity similar to COSphox cells transiently transfected with WT p67phox; therefore, these modifications are not associated with genetic deficiencies in NADPH oxidase . In conclusion, the COSphox system represents an easily transfectable model for analysis of NADPH oxidase function in intact cells . The analysis of mutant derivatives of p67phox provides insight into molecular mechanisms by which this subunit regulates the NADPH oxidase. Nat Rev Microbiol, 2004 Dec, 2(12), 979 - 83 Epidemiological interpretation of antibiotic resistance studies - what are we missing? Schwaber MJ, De-Medina T, Carmeli Y. Antimicrobial resistance is an emerging public-health threat . Studies of the relationship between antibiotic use and resistance, as well as surveillance programmes, examine changes in the proportion of isolates that are resistant . Although proportions are helpful to the clinician prescribing empirical therapy, proportion-based analyses can be misleading to the public-health professional as they can yield biased estimates . Proportions do not adequately reflect the burden of resistance, a measure often of interest in public health . A more appropriate measure of this burden is the rate of isolation of resistant organisms, that is, the absolute number of resistant isolates in a population over time. Emerg Infect Dis, 2004 Nov, 10(11), 1924 - 30 Enhanced Identification of Postoperative Infections among Inpatients; Yokoe DS; We evaluated antimicrobial exposure, discharge diagnoses, or both to identify surgical site infections (SSI) . This retrospective cohort study in 13 hospitals involved weighted, random samples of records from 8,739 coronary artery bypass graft (CABG) procedures, 7,399 cesarean deliveries, and 6,175 breast procedures . We compared routine surveillance to detection through inpatient antimicrobial exposure (>9 days for CABG, >2 days for cesareans, and >6 days for breast procedures), discharge diagnoses, or both . Together, all methods identified SSI after 7.4% of CABG, 5.0% of cesareans, and 2.0% of breast procedures . Antimicrobial exposure had the highest sensitivity, 88%-91%, compared with routine surveillance, 38%-64% . Diagnosis codes improved sensitivity of detection of antimicrobial exposure after cesareans . Record review confirmed SSI after 31% to 38% of procedures that met antimicrobial surveillance criteria . Sufficient antimicrobial exposure days, together with diagnosis codes for cesareans, identified more postoperative SSI than routine surveillance methods . This screening method was efficient, readily standardized, and suitable for most hospitals. Emerg Infect Dis, 2004 Nov, 10(11), 1895 - 9 Trachoma decline and widespread use of antimicrobial drugs; Chidambaram JD; Trachoma is disappearing in many parts of the world, even in the absence of specific control programs . Following mass antimicrobial drug treatments for trachoma in western Nepal, the prevalence of trachoma declined far more rapidly than could be attributed to the control program alone . Pharmacy surveys in the same region found that children received more antichlamydial drugs from sources outside the trachoma program than they did from the program itself . We demonstrate that high background antimicrobial drug use may be responsible for much of the observed decline in trachoma and discuss its potential role in eliminating this infectious disease. Nature, 2004 Nov 18, 432(7015), 401 - 5 A FADD-dependent innate immune mechanism in mammalian cells; Balachandran S et al.; Vertebrate innate immunity provides a first line of defence against pathogens such as viruses and bacteria . Viral infection activates a potent innate immune response, which can be triggered by double-stranded (ds)RNA produced during viral replication . Here, we report that mammalian cells lacking the death-domain-containing protein FADD are defective in intracellular dsRNA-activated gene expression, including production of type I (alpha/beta) interferons, and are thus very susceptible to viral infection . The signalling pathway incorporating FADD is largely independent of Toll-like receptor 3 and the dsRNA-dependent kinase PKR, but seems to require receptor interacting protein 1 as well as Tank-binding kinase 1-mediated activation of the transcription factor IRF-3 . The requirement for FADD in mammalian host defence is evocative of innate immune signalling in Drosophila, in which a FADD-dependent pathway responds to bacterial infection by activating the transcription of antimicrobial genes . These data therefore suggest the existence of a conserved pathogen recognition pathway in mammalian cells that is essential for the optimal induction of type I interferons and other genes important for host defence. J Biol Chem . 2004 Nov 17; {Epub ahead of print} Spermine causes loss of innate immune response to Helicobacter pylori by inhibition of inducible nitric oxide synthase translation; Bussiere FI et al.; Helicobacter pylori infection of the stomach elicits a vigorous but ineffective host immune and inflammatory response, resulting in persistence of the bacterium for the life of the host . We have reported that in macrophages, H . pylori upregulates inducible NO synthase (iNOS) and antimicrobial NO production, but in parallel there is induction of arginase II, generating ornithine, and an induction of ornithine decarboxylase (ODC), generating polyamines . Spermine, in particular, has been shown to restrain immune response in activated macrophages by inhibiting proinflammatory gene expression . We hypothesized that spermine could prevent the antimicrobial effects of NO by inhibiting iNOS in macrophages activated by H . pylori . Spermine did not affect the upregulation of iNOS mRNA levels, but in a concentration-dependent manner significantly attenuated iNOS protein levels and NO production . Reduction in iNOS protein was due to inhibition of iNOS translation and not due to iNOS degradation . ODC knockdown with small interfering (si) RNA resulted in increased H . pylori-stimulated iNOS protein expression and NO production without altering iNOS mRNA levels . When macrophages were cocultured with H . pylori, killing of bacteria was enhanced by transfection of ODC siRNA and prevented by addition of spermine . These results identify a mechanism of immune dysregulation induced by H . pylori in which stimulated spermine synthesis by the arginase-ODC pathway inhibits iNOS translation and NO production, leading to persistence of the bacterium and risk for peptic ulcer disease and gastric cancer. Int J Mol Med, 2004 Dec, 14(6), 1023 - 7 Pathophysiological role of human beta-defensins 2 in gastric mucosa; Ohara T et al.; Human beta-defensins (HBDs) recognized in the stomach include HBD1, which is the constitutional human beta-defensin (HBD), and HBD-2 and HBD-4, which are inducible HBDs . HBD-2 is an antimicrobial peptide that is involved in host defences against bacterial infections, such as Helicobacter pylori (H.pylori) in infection of the gastric mucosal epithelium . We examined the pathophysiological role of HBD-2, besides their roles as antimicrobial peptides . The materials used for the study consisted of gastric mucosal tissue specimens collected endoscopically from patients with conditions such as chronic gastritis associated with H . pylori infection, and gastric ulcers and gastritis due to non-steroidal anti-inflammatory drugs (NSAIDs) with or without H . pylori infection . We investigated the expression of HBD-2 and NF-kappaB by RT-PCR and immunoblotting, and the relation between the localization of HBD-2 and follicular dendritic cells (FDCs) by immunohistochemistry . Expression of HBD-2 was recognized in all the mucosal tissue specimens, irrespective of the presence or absence of H . pylori infection . All of the mucosal specimens expressing HBD-2 also revealed expression of NF-kappaB . In consecutive immunohisto-chemical staining, while expression of HBD-2 was observed in the gastric mucosal epithelium, FDCs were found to be localized in the lamina propria mucosae under the epithelial cell layer . These data suggested that in addition to being antimicrobial peptides, HBD-2 may also have a pathophysiological role as proinflammatory mediators, and that the HBD may act as proinflammatory mediators in concert with the dendritic cells (DC) by transmitting a signal from the mucosal surface to the lamina propria mucosae, which seems to be the original site of gastric mucosal damage. Am J Obstet Gynecol, 2004 Nov, 191(5), 1678 - 87 The novel antimicrobial peptide beta3-defensin is produced by the amnion: a possible role of the fetal membranes in innate immunity of the amniotic cavity; Buhimschi IA et al.; BACKGROUND: Innate immunity evolved to eliminate microorganisms before, or after their entry into the tissues, but before enough antigen is available to activate an adaptive, immune response . Innate immunity is so successful that the majority of encountered microbes are neutralized . The beta-defensins are antimicrobial peptides produced by skin and mucosal surfaces and are an integral part of the innate immune system . The ability of the amnion cells, which are epithelial derivatives, to produce antimicrobial beta-defensins has not been explored . OBJECTIVE: This study was undertaken to test the hypothesis that amnion cells synthesize beta-defensins under either basal or stimulated conditions . METHODS: Amnion epithelial FL cells (ATCC CCL 62) were cultured in Ham's F12 and Dulbecco's modified Eagle medium plus 10% fetal calf serum until confluence, then replated into 24-well plates at 1.5 million cells per well . Cells from triplicate wells were harvested after 1, 3, 6, and 24 hours of exposure to microbial wall components (lipopolysaccharide {LPS}: 1 microg/mL or peptidoglycan {PG}: 10 microg/mL) . Reverse transcription real-time polymerase chain reaction was performed with the use of human-specific primers for beta1, beta2, beta3, and beta4 defensins to compare basal messenger RNA (mRNA) levels of defensins and in response to treatment . beta-actin was used for standardization . Protein expression was investigated by immunofluorescence of the cells in culture, and by immunohistochemistry in paraffin sections of human fetal membranes from pregnancies with or without histologic chorioamnionitis . RESULTS: Amnion FL cells expressed mRNA for all known beta-defensins with beta3-defensin mRNA levels significantly higher compared with others ( P < .001, 1-way analysis of variance {ANOVA}) . beta3 was the only beta-defensin whose mRNA was upregulated in response to the microbial mimics LPS (1-way ANOVA, P = .019) and PG (1-way ANOVA, P = .011) . Immunofluorescence confirmed that beta3-defensin protein was present in cultured amnion cells, and upregulated in response to PG and LPS in distinct cells . Similarly, in tissue sections of human fetal membranes amnion epithelium was intensely positive for beta3-defensin protein by immunohistochemistry . Conspicuous beta3-defensin staining was also detected in the chorio-decidua . CONCLUSION: Amnion cells have the ability to produce beta-defensins . The beta3-defensin appears to be the predominant epithelial defensin expressed . Its induction by microbial mimics suggests that the amniotic epithelium may play a role in the innate immunity of the amniotic cavity. Clin Orthop, 2004 Oct, 1(427), 18 - 21 Porcine Small Intestine Submucosa Does Not Show Antimicrobial Properties; Holtom PD et al.; The goal of this study is to examine whether porcine small intestine submucosa (SIS) exhibits antimicrobial properties in a standard in vitro system, without pretreatment with acetic acid or extraction of soluble proteins . Previous animal studies suggest that porcine SIS may have inherent antibiotic properties . Using the guidelines for disk diffusion susceptibility testing by Bauer, 17/64-inch diameter disks made of porcine small intestine submucosa and of gortex were compared with standard antibiotic-impregnated disks against six organisms . The zone of inhibition was measured after 24 hours and minimum bacterial concentrations were determined by serial dilutions of a solution in which porcine small intestine submucosa was allowed to elute for 24 hours . Neither porcine SIS or gortex discs caused inhibition of the growth of any organism . The porcine small intestine submucosa discs showed bacterial growth on top of the discs whereas the gortex did not . Neither the dilutional concentrations of the porcine small intestine submucosa eluent nor the gortex eluent inhibited the growth of any organism . These findings suggest that the porcine small intestine submucosa does not have intrinsic antimicrobial properties . The growth of bacteria on top of the porcine small intestine submucosa suggests that porcine small intestine submucosa itself may provide a favorable environment for the growth of bacteria . More research is necessary to decide what role porcine small intestine submucosa plays in the treatment of infected surgical sites. Blood . 2004 Nov 16; {Epub ahead of print} Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity; Munder M et al.; The balance of arginine metabolism via nitric oxide synthase (NOS) or arginase is an important determinant of the inflammatory response of murine macrophages and dendritic cells . Here we analysed the expression of the isoform arginase I in human myeloid cells . Using healthy donors and arginase I-deficient patients, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of pro- and antiinflammatory stimuli in vitro . We demonstrate that arginase I is localised in azurophil granules of neutrophils and constitutes a novel antimicrobial effector pathway, likely through arginine depletion in the phagolysosome . Our findings demonstrate important differences between murine and human leukocytes with respect to regulation and function of arginine metabolism via arginase. Ann Clin Microbiol Antimicrob . 2004 Nov 16;3(1):25. Laboratory diagnosis and susceptibility profile of Helicobacter pylori infection in the Philippines; Destura RV et al.; BACKGROUND: Helicobacter pylori diagnosis and susceptibility profile directs the applicability of recommended treatment regimens in our setting . To our knowledge, there is no published data on the culture and local susceptibility pattern of Helicobacter pylori in the Philippines . METHODS: 52 dyspeptic adult patients undergoing endoscopy from the Outpatient Gastroenterology clinic of the University of the Philippines-Philippine General Hospital underwent multiple gastric biopsy and specimens were submitted for gram stain, culture, antimicrobial sensitivity testing, rapid urease test and histology . Antimicrobial susceptibility testing was done by Epsilometer testing (Etest) method against metronidazole, clarithromycin, amoxicillin, and tetracycline . RESULTS: Sixty percent (60%) of the study population was positive for H . pylori infection (mean age of 44 years +/- 13), 70% were males . H . pylori culture showed a sensitivity of 45% (95% CI {29.5-62.1}), specificity of 98% (95%CI {81.5-100%}), positive likelihood ratio of 19.93 (95% CI {1.254-317.04}) and a negative likelihood ratio of 0.56 (95% CI {0.406-0.772}) . All H . pylori strains isolated were sensitive to metronidazole, clarithromycin, amoxicillin and tetracycline . CONCLUSION: Knowledge of the antibiotic susceptibility patterns in our setting allows us to be more cautious in the choice of first-line agents . Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. Immunol Rev, 2004 Dec, 202, 96 - 105 IL-12 and IL-23: master regulators of innate and adaptive immunity; Langrish CL et al.; Initiation of an effective immune response requires close interactions between innate and adaptive immunity . Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell-derived factors regulate the immune system to protect the host from infections and prevent tumor development . In this review, we focus on the function of interleukin (IL)-23, a new member of the IL-12 family of regulatory cytokines produced by activated macrophages and dendritic cells . We propose that IL-12 and IL-23 promote two distinct immunological pathways that have separate but complementary functions . IL-12 is required for antimicrobial responses to intracellular pathogens, whereas IL-23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation . These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression. Clin Infect Dis, 2004 Sep 1, 39 Suppl 3, S151 - 8 Acute community-acquired bacterial sinusitis: continuing challenges and current management; Sande MA et al.; Acute sinusitis is one of the most common infections seen in general clinical practice . The most common cause of acute sinusitis is viral; however, many patients receive a prescription for an antibiotic . Such injudicious prescribing habits have a major impact on health care costs, contribute to the increasing prevalence of drug-resistant strains of common respiratory pathogens, and reflect many of the challenges in differentiating viral and bacterial disease . Sinus puncture and culture of the aspirate, the diagnostic reference standard in the research setting, are not appropriate for routine clinical practice . However, certain clinical signs and symptoms that do not improve or that worsen after 7-10 days are currently accepted criteria for diagnosis of bacterial sinusitis . Accurate diagnosis can select patients who would benefit most from antimicrobial use . Antimicrobial agents should be selected on the basis of local resistance patterns, and their spectrum of activity should cover the common bacterial pathogens, including resistant strains. Mar Biotechnol (NY), 2004 Jul-Aug, 6(4), 386 - 99 Epub 2004 Aug 06. Suppression subtractive hybridization cDNA libraries to identify differentially expressed genes from contrasting fish habitats; Straub PF et al.; Suppression subtractive hybridization complementary DNA libraries identified differentially expressed genes in liver tissue of winter flounder collected from the highly impacted Raritan-Hudson estuary versus those from less industrialized estuaries farther south in New Jersey . Distinct transcript profiles emerged in the fish from these different habitats . A total of 251 clones from the forward (upregulated with anthropogenic impact) and reverse (downregulated with anthropogenic impact) subtracted libraries were sequenced . In the upregulated library immune response transcripts, including complement C-3, C-7, factor H, factor Bf/C2, differentially regulated trout protein 1, and the antimicrobial hepcidin, indicated the pollution-impacted fish were under a high viral or bacterial load . Transcripts for cytochrome P450 1A, P450 3A, and glutathione S-transferase, important components of phase I and II metabolism of xenobiotics, were found in the upregulated-with-pollution library . Vitellogenins I and II and egg envelope protein (zp) appeared to be downregulated . A homologue of the tumor suppressor p33(ING1) (down) and hepatocyte growth factor-like protein (up) may indicate liver damage or hepatocellular carcinoma or hepatoma . These expression patterns, confirmed by quantitative polymerase chain reaction, indicate that transcript analysis is a useful method for assessing the health of local habitats and the organisms therein. Farmaco, 2004 Nov, 59(11), 893 - 901 Synthesis of some 3-(arylalkylthio)-4-alkyl/aryl-5-(4-aminophenyl)-4H-1,2,4-triazole derivatives and their anticonvulsant activity; Kucukguzel I et al.; A series of novel 3-{{(substituted phenyl)methyl}thio}-4-alkyl/aryl-5-(4-aminophenyl)-4H-1,2,4-triazoles 11-20 and several related Schiff's bases, 3-{{(substituted phenyl)-methyl}thio}-4-alkyl/aryl-5-{{{(substituted phenyl/5-nitro-2-furyl)methylene}amino}-phenyl}-4H-1,2,4-triazoles 21-31 were synthesized for evaluation of their biological properties . Structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis . All compounds were evaluated for their anticonvulsant activity by maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and neurotoxicity (NT) screens . A number of triazole derivatives, exhibited protection after intraperitoneal administration at the dose of 100 and 300 mg/kg in one or both models employed . Compounds 12, 13 and 14 were subjected to oral MES screening in rats at 30 mg/kg and were observed to protect 50% of the animals employed in the experiment . Antimicrobial and antituberculosis activity of these compounds 11-31 were also screened . Some of the tested compounds showed marginal activity against M . tuberculosis H37 Rv. Ann Clin Microbiol Antimicrob . 2004 Nov 15;3(1):24. Primary lymphocutaneous nocardiosis in an immunocompetent patient; Maraki S et al.; BACKGROUND: Nocardia brasiliensis is a rare human pathogen usually associated with localized cutaneous infections . CASE PRESENTATION: We report a case of primary lymphocutaneous Nocardia brasiliensis infection developed after a bone fracture of the left hand of an otherwise healthy 32-year-old man . Treatment with trimethoprim-sulfamethoxazole given for a total of three months combined with surgical debridement resulted in complete resolution of the infection . CONCLUSION: Nocardiosis should be part of the differential diagnosis in patients with sporotrichoid infection, particularly those with a history of outdoor injury . Culture of the affected tissue and antimicrobial susceptibility testing of the isolate should be performed for diagnosis and treatment. HIV Med, 2004 Nov, 5(6), 431 - 6 Epidemiological, clinical and therapeutic features of AIDS-related Mycobacterium kansasii infection during the HIV pandemic: an 11-year follow-up study; Manfredi R et al.; OBJECTIVES: Optimal diagnosis and timely treatment of atypical mycobacteriosis, and especially Mycobacterium kansasii disease, remain a serious challenge for clinicians engaged in the management of the immunocompromised host . METHODS AND RESULTS: From more than 2700 hospitalizations (over 1800 patients) attributable to HIV-associated disorders over an 11-year period, 12 patients were found to have a confirmed M . kansasii infection . This reflects the recent reduction in the frequency of this HIV-related complication, which virtually disappeared after the introduction of potent antiretroviral combinations in 1996 . In the early 1990s, the lack of effective antiretroviral regimens made frequent the association with AIDS, a mean CD4 lymphocyte count of nearly 20 cells/microL, and an extremely variable chest X-ray features . The recent detection of a further case was attributable to late recognition of very advanced HIV disease, complicated by multiple opportunistic disorders . CONCLUSIONS: Mycobacterium kansasii respiratory or disseminated infection continues to occur, and poses diagnostic problems in terms of late or missed identification as a result of slow culture and frequently concurrent opportunistic disease . Serious therapeutic difficulties also arise from the unpredictable in vitro antimicrobial susceptibility profile of these organisms, and from the need to start an effective combination therapy that does not interfere with other medications as soon as possible. Curr Protein Pept Sci, 2004 Oct, 5(5), 365 - 71 Theta-defensins: cyclic antimicrobial peptides produced by binary ligation of truncated alpha-defensins; Selsted ME; The first cyclic peptide discovered in animals is an antimicrobial octadecapeptide that is expressed in leukocytes of rhesus monkeys . The peptide, termed rhesus Theta-defensin 1 (RTD-1) is the prototype of a new family of antimicrobial peptides, which like the previously characterized alpha- and beta-defensin families, possesses broad spectrum microbicidal activities against bacteria, fungi, and protects mononuclear cells from infection by HIV-1 . The cyclic Theta-defensin structure is essential for a number of its antimicrobial properties, as demonstrated by the markedly reduced microbicidal activities of de-cyclized Theta-defensin analogs . Genetic and biochemical experiments disclosed that the biosynthesis of RTD-1 results from the head-to-tail joining of two nine-amino acid peptides, each of which is donated by a separate precursor polypeptide, which are in fact C-terminally truncated pro-alpha-defensins . Alternate combinations of the two nonapeptides generate two additional macaque Theta-defensins, RTD-2 and RTD-3 . Humans do not express Theta-defensin peptides, but mRNAs encoding at least two Theta-defensins are expressed in human bone marrow . However, in each case the open reading frame is interrupted by a stop codon in the signal peptide-coding region . The mature Theta-defensin peptide is a two-stranded beta-sheet that, like the alpha- and beta-defensins, is stabilized by three disulfides . However, the parallel orientation of the Theta-defensin disulfide arrangement allows for substantial flexibility around its short axis . Unlike alpha- and beta-defensins, RTD-1 lacks an amphiphilic topology . This may partially explain the unusual interaction between Theta-defensins and phospholipid bilayers. Curr Protein Pept Sci, 2004 Oct, 5(5), 331 - 40 Anti-HIV cyclotides; Gustafson KR et al.; The cyclotides are a recently discovered, structurally unique family of bioactive plant peptides . Their discovery spawned a series of structural analyses, synthetic efforts, and studies to define the biosynthesis and biological properties of these novel peptide metabolites . Cyclotides have a head-to-tail cyclized amino acid backbone and a conserved cystine knot motif that provides an extremely stable structural framework . They all share a common global fold and are highly resistant to denaturation and to cleavage by proteolytic enzymes . However, these macrocyclic peptides are quite permissive to amino acid substitutions or additions in several peripheral loop regions, since changes in these loops do not alter the core cyclotide structure . These features make cyclotides attractive templates for incorporating desired amino acid sequences and then delivering these peptide sequences in a well defined, highly stable framework . Cyclotides likely function in a defensive role in the source plants since they exhibit a broad spectrum of antimicrobial activity and are detrimental to the growth and survival of herbivorous insects . Cyclotides are gene-encoded polypeptides that are cleaved from larger precursor proteins and then cyclized . This review summarizes research done on a subset of cyclotides that were discovered due to their HIV inhibitory properties . It details the isolation and characterization of these compounds and describes this work in the context of our current state of knowledge of the entire cyclotide family. Curr Protein Pept Sci, 2004 Oct, 5(5), 297 - 315 Discovery, structure and biological activities of the cyclotides; Craik DJ et al.; The cyclotides are a family of small disulfide rich proteins that have a cyclic peptide backbone and a cystine knot formed by three conserved disulfide bonds . The combination of these two structural motifs contributes to the exceptional chemical, thermal and enzymatic stability of the cyclotides, which retain bioactivity after boiling . They were initially discovered based on native medicine or screening studies associated with some of their various activities, which include uterotonic action, anti-HIV activity, neurotensin antagonism, and cytotoxicity . They are present in plants from the Rubiaceae, Violaceae and Cucurbitaceae families and their natural function in plants appears to be in host defense: they have potent activity against certain insect pests and they also have antimicrobial activity . There are currently around 50 published sequences of cyclotides and their rate of discovery has been increasing over recent years . Ultimately the family may comprise thousands of members . This article describes the background to the discovery of the cyclotides, their structural characterization, chemical synthesis, genetic origin, biological activities and potential applications in the pharmaceutical and agricultural industries . Their unique topological features make them interesting from a protein folding perspective . Because of their highly stable peptide framework they might make useful templates in drug design programs, and their insecticidal activity opens the possibility of applications in crop protection. Curr Pharm Des, 2004, 10(26), 3213 - 20 Fluoroquinolones as chemotherapeutics against mycobacterial infections; Jacobs MR; The antimicrobial agents used in the treatment of mycobacterial infections have remained largely unchanged for several decades . Primary treatment of tuberculosis relies on four drugs, isoniazid, a rifamycin, pyrazinamide, and ethambutol (or streptomycin), and generally results in >95% cure in uncomplicated tuberculosis infection . Drug resistance greatly complicates treatment of this disease . Treatment of tuberculosis caused by multiply drug-resistant strains with "second-line" drugs remains complex, and is generally tailored to the individual patient and strain . Several of the fluoroquinolones have shown promise as second line drugs for treatment of active disease and, in combination with clarithromycin or azithromycin, ethambutol, and other agents, for treatment of Mycobacterium avium complex infection . While large clinical trials are not possible with second line drugs, clinical treatment data are available and suggest that the quinolones have various degrees of promise in treatment of these infections . Bacterial type II DNA topoisomerases, DNA gyrase and topoisomerase IV, are the targets of quinolones, and provide the genetic basis for quinolone activity in mycobacteria . Mutations in these enzymes results in resistance, and characterization of resistant mutants allows correlation of genotype with susceptibility phenotype . Structure-activity relationship studies have provided further insight into optimal use of quinolones in mycobacterial infections . Care should be taken in treating pneumonia with fluoroquinolones if there is a degree of suspicion of tuberculosis, since quinolone monotherapy may rapidly select for quinolone resistance, thereby removing that class of antibiotic from the small range of treatment options. Curr Pharm Des, 2004, 10(25), 3067 - 80 Cellular and molecular effects of macrolides on leukocyte function; Labro MT; Macrolide antimicrobials have stimulated worldwide interest owing to their therapeutic effects in various inflammatory, apparently non infectious, diseases . Abundant data are now available on their interactions with host cell (specially phagocyte) functions . Modulation of oxidant production by neutrophils and of pro-inflammatory cytokine synthesis and release by leukocytes are the two main effects observed in vitro . However, despite an extensive literature, many questions remain, such as the cellular/microbial target(s) of macrolide action, the critical chemical structure(s), and the usefulness of combining antimicrobial and anti-inflammatory properties, which during long-term treatment, could lead to increased microbial resistance . Also, because of the multiplicity of macrolide effects on different cell subsets, a unifying hypothesis for macrolide interactions with host cells is lacking . Novel analytical methods will certainly lead to new macrolide-based therapeutic strategies in cancer and inflammation. Curr Pharm Des, 2004, 10(25), 3045 - 53 The macrolide antibiotics: a pharmacokinetic and pharmacodynamic overview; Jain R et al.; The macrolide antimicrobial family is comprised of 14, 15 and 16 member-ringed compounds that are characterized by similar chemical structures, mechanisms of action and resistance, but vary in the different pharmacokinetic parameters, and spectrum of activity . The macrolides accumulate in many tissues such as the epithelial lining fluid and easily enter the host defense cells, predominantly macrophages and polymorphonuclear leukocytes (PMNs) . Concentrations of the macrolides in respiratory tract tissues and extracellular fluids are in almost all cases higher than simultaneously measured serum concentrations, making them useful for respiratory tract infections . This review will focus on pharmacokinetic and pharmacodynamic aspects of the clinical relevant macrolides including azithromycin, clarithromycin, dirithromycin, erythromycin and roxithromycin. Med Dosw Mikrobiol, 2004, 56(2), 199 - 209 {Evaluation of selected alcoholic antiseptics activity against clinical bacterial strains}; Bocian E et al.; The aim of this study was to evaluate antimicrobial activity of selected alcoholic antiseptics against clinical strains, which possessed in majority a high level of drug resistance: MRSA (7), MSSA (3), E . coli: (9): strains producing ESBL (4), P . aeruginosa: (4), E . cloacae: (3), K . pneumoniae: (3) . These strains were defined by MIC value, using antibiotic agar dilution method according to NCCLS . Fourteen alcoholic antiseptics were used in this study . Beside alcohol, they contained other active substances like iodine, hydrogen peroxide, chlorhexidine . Some additional agents were included for easier application, such as: gelling, moisturizing, aromatic or coloring substances . The objective of this study was also to determine the dependence of bactericidal activity on preparations (concentration) . Product undiluted and diluted two and four times in water was analyzed according to prEN 12054 standard; 30 seconds and 1 minute contact time was used . The obtained data indicate that all tested undiluted antiseptics possessed bactericidal activity described by producers . However antiseptics (dilution leads to decrease and even loss of bactericidal activity . Two-times dilution of gel almost completely inactivated the product . Antimicrobial activity after 30 seconds of contact time was not affected by presence of additional agents in the tested antiseptics. J Chromatogr A, 2004 Oct 22, 1053(1-2), 161 - 72 Monitoring the hydrophilicity/hydrophobicity of amino acid side-chains in the non-polar and polar faces of amphipathic alpha-helices by reversed-phase and hydrophilic interaction/cation-exchange chromatography; Hodges RS et al.; The ability to monitor precisely the hydrophobicity/hydrophilicity effects of amino acid substitutions in both the non-polar and polar faces of amphipathic alpha-helical peptides is critical in such areas as the rational de novo design of more effective antimicrobial peptides . The present study reports our initial results of employing the complementary separation modes of reversed-phase high-performance liquid chromatography (RP-HPLC) and hydrophilic interaction/cation-exchange chromatography (HILIC/CEX) to monitor the effect on apparent peptide hydrophilicity/hydrophobicity and amphipathicity of substituting single L- or D-amino acids into the centre of the non-polar or polar faces of a 26-residue biologically active amphipathic alpha-helical peptide, V681 . Our results clearly show that RP-HPLC and HILIC/CEX are best suited for resolving amphipathic peptides where substitutions are made in the non-polar and polar faces, respectively . Further, RP-HPLC and HILIC/CEX were demonstrated to be excellent monitors of hydrophilicity/hydrophobicity variations where amino acid substitutions were made in these respective faces . We believe these complementary high-performance modes offer excellent potential for rational design of novel amphipathic alpha-helical biologically active peptides. Crit Care Med, 2004 Nov, 32(11 Suppl), S578 - 90 Sepsis associated with immunosuppressive medications: an evidence-based review; Gea-Banacloche JC et al.; OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sepsis associated with immunosuppressive medications that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis . DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee . METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum . We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade . Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al . on p . S591 . CONCLUSION: Immunosuppressed patients, by definition, are susceptible to a wider spectrum of infectious agents than immunologically normal patients and, thus, require a broader spectrum antimicrobial regimen when they present with sepsis or septic shock . Special expertise managing immunosuppressed patient populations is needed to predict and establish the correct diagnosis and to choose appropriate empiric and specific agents and maximize the likelihood that patients will survive these microbial challenges. Crit Care Med, 2004 Nov, 32(11 Suppl), S495 - 512 Antimicrobial therapy for patients with severe sepsis and septic shock: an evidence-based review; Bochud PY et al.; OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for antimicrobial therapy for patients with severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis . DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee . METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum . We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade . Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al . on p . S591 . CONCLUSION: Since the prompt institution of therapy that is active against the causative pathogen is one of the most important predictors of outcome, clinicians must establish a system for rapid administration of a rationally chosen drug or combination of drugs when sepsis or septic shock is suspected . The expanding number of antibacterial, antifungal, and antiviral agents available provides opportunities for effective empiric and specific therapy . However, to minimize the promotion of antimicrobial resistance and cost and to maximize efficacy, detailed knowledge of the likely pathogens and the properties of the available drugs is necessary for the intensivist. Mol Biotechnol, 2004 Nov, 28(3), 185 - 9 Expression of an antimicrobial peptide identified in the male reproductive system of rats; Sun XJ et al.; Bin1b is a beta-defensins-like molecule originally isolated from the rat epididymis . Owing to its bactericidal activity, Bin1b may have therapeutic properties suitable for the treatment of sexually transmitted diseases . The amino terminus of the mature Bin1b peptide contains a conserved myristoylated Gly residue . We studied the requirement of the terminal myristoylated Gly residue in the bactericidal activity of Bin1b and found that the terminal myristoylated Gly residue is not essential for the bactericidal activity . In addition, we expressed the tandem repeats of Bin1b in Escherichia coli and found that two tandem repeats of Bin1b protein were successfully expressed . The bacterially expressed tandem Bin1b repeats may be used in a diverse array of biochemical and cell biological studies. J Biol Chem, 2005 Jan 21, 280(3), 2002 - 11 Epub 2004 Nov 12. Structure-Activity Relationships of Diastereomeric Lysine Ring Size Analogs of the Antimicrobial Peptide Gramicidin S: MECHANISM OF ACTION AND DISCRIMINATION BETWEEN BACTERIAL AND ANIMAL CELL MEMBRANES; Prenner EJ et al.; Structure-activity relationships were examined in seven gramicidin S analogs in which the ring-expanded analog GS14 {cyclo-(VKLKVdYPLKVKLdYP)} is modified by enantiomeric inversions of its lysine residues . The conformation, amphiphilicity, and self-association propensity of these peptides were investigated by circular dichroism spectroscopy and reversed phase high performance liquid chromatography . (31)P nuclear magnetic resonance spectroscopic and dye leakage experiments were performed to evaluate the capacity of these peptides to induce inverse nonlamellar phases in, and to permeabilize phospholipid bilayers; their growth inhibitory activity against the cell wall-less mollicute Acholeplasma laidlawii B was also examined . The amount and stability of beta-sheet structure, effective hydrophobicity, propensity for self-association in water, ability to disrupt the organization of phospholipid bilayers, and ability to inhibit A . laidlawii B growth are strongly correlated with the facial amphiphilicity of these GS14 analogs . Also, the magnitude of the parameters segregate these peptides into three groups, consisting of GS14, the four single inversion analogs, and the two multiple inversion analogs . The capacity of these peptides to differentiate between bacterial and animal cell membranes exhibits a biphasic relationship with peptide amphiphilicity, suggesting that there may only be a narrow range of peptide amphiphilicity within which it is possible to achieve the dual therapeutic requirements of high antibiotic effectiveness and low hemolytic activity . These results were rationalized by considering how the physiochemical properties of these GS14 analogs are likely to be reflected in their partitioning into lipid bilayer membranes. Vet Immunol Immunopathol, 2004 Dec 28, 102(4), 351 - 62 Fc receptors in livestock species; Kacskovics I; Many of the receptors for the Fc domain of immunoglobulins in cattle, sheep, pigs and horses have been cloned and characterized recently . This review summarises recent developments and relates them to the current understanding of the primary structure, cellular specificity and binding properties of Fc receptors (FcRs) . Although there is an obvious overall similarity to their human and mouse counterparts, some Fc receptors in domestic animals are unusual, perhaps most notably the bovine Fcgamma2R, which although related to other mammalian FcgammaRs, belongs to a novel gene family and the porcine FcgammaRIIIA, which associates with a molecule that contains significant homology to the cathelin family of antimicrobial proteins . Accumulating data suggest the possibility of a different role for the FcRn in ruminants, which may secrete IgG onto the mucosal surfaces, rather than absorbing it, as was suggested by mouse studies . These differences may be linked to the diversity of immunoglobulin classes in different mammalian species, and may contribute to different immune functions . The observations made so far emphasize the importance of elucidating and analyzing the roles of these molecules within the immune system of each host animal, rather than inferring roles from conclusions made in human and mouse studies . A better understanding of Fc receptor expression on immune effector cells should help in developing new immunization protocols, while knowledge of the Fc receptors involved in immunoglobulin transport, especially in the mammary gland, may help to develop new products which could be used not only for veterinary purposes but perhaps also for human therapy. Am J Med, 2004 Nov 15, 117(10), 726 - 31 Effects of guideline-concordant antimicrobial therapy on mortality among patients with community-acquired pneumonia; Mortensen EM et al.; PURPOSE: National practice guidelines have recommended specific initial empiric antimicrobial regimens for patients with community-acquired pneumonia . Our aim was to determine the association between the use of guideline-concordant antimicrobial therapy and 30-day mortality in patients with pneumonia . METHODS: We conducted a retrospective cohort study at two tertiary teaching hospitals . Eligible patients were admitted with a diagnosis of community-acquired pneumonia, had a chest radiograph consistent with pneumonia, and had a discharge diagnosis of pneumonia . All eligible patients were identified and a random sample was abstracted . We determined whether the use of guideline-concordant antibiotics was associated with 30-day mortality in an analysis that adjusted for potential confounders using propensity scores . RESULTS: Information was obtained on 420 patients with pneumonia . The mean (+/- SD) age was 63 +/- 16 years, 355 were men, and 82 patients were initially admitted to the intensive care unit . At 30 days after presentation, 41 patients (9.8%) had died: 21 of 97 (21.7%) in the non-guideline-concordant group and 20 of 323 (6.2%) in the guideline-concordant group . Antibiotics were concordant with national guidelines in 323 patients . In the regression analysis, after adjustment for the propensity score, failure to comply with antimicrobial therapy guidelines was associated with increased 30-day mortality (odds ratio = 5.7; 95% confidence interval: 2.0 to 16.0) . CONCLUSION: Receipt of antimicrobial regimens concordant with national published guidelines may reduce 30-day mortality among patients hospitalized with pneumonia. Z Naturforsch {C}, 2004 Sep-Oct, 59(9-10), 657 - 62 Antimicrobial activity of fractions and compounds from Calophyllumbrasiliense (Clusiaceae/Guttiferae); Pretto JB et al.; Calophyllum brasiliense (Clusiaceae/Guttiferae) is a native Brazilian medicinal plant traditionally used against several diseases, including infectious pathologies . Crude methanolic extracts (CME) and two fractions, denoted non-polar (soluble in chloroform) and polar (nonsoluble in chloroform), were prepared from different parts of the plant (roots, stems, leaves, flowers and fruits) and studied . The following compounds were isolated and tested against pathogenic bacteria and yeasts by determination of the minimal inhibitory concentration (MIC): brasiliensic acid (1), gallic acid (2), epicatechin (3), protocatechuic acid (4), friedelin (5) and 1,5-dihydroxyxanthone (6) . The results indicated that all the parts of the plant exhibited antimicrobial activity against Gram-positive bacteria, which are selectively inhibited by components of C . brasiliense . No activity was observed against Gram-negative bacteria and yeasts tested . Regarding the isolated compounds, substance 4 showed antimicrobial activity against all the tested microorganisms, whereas compound 6 exhibited antimicrobial activity only against Gram-positive bacteria . The results from the current study confirm and justify the popular use of this plant to treat infectious processes. Trends Microbiol, 2004 Dec, 12(12), 555 - 61 Surface polysaccharides enable bacteria to evade plant immunity; D'Haeze W et al.; Plants have an immune system to perceive pathogenic or potentially beneficial bacteria . Aspects of perception, signal transduction and the responses that the plant produces resemble features of innate immunity observed in animals . Plant reactions are various and include the production of antimicrobial compounds . Bacteria that are successful in establishing pathogenic or symbiotic interactions have developed multiple ways to protect themselves . We review the general importance of bacterial surface polysaccharides in the evasion of plant immune responses and elaborate on their role in protecting symbiotic bacteria against toxic reactive oxygen species during invasion of the host plant. Curr Infect Dis Rep, 2004 Dec, 6(6), 457 - 461 Antimicrobial Selection in the Treatment of Pyelonephritis; Brown PD; Pyelonephritis is a common clinical entity, although accurate data regarding the true prevalence of this infection are lacking . Acute pyelonephritis is associated with significant morbidity and even mortality . There are very few randomized controlled clinical trials that have addressed the optimal management strategies and antimicrobial therapy for this infection . Increasing resistance among uropathogens, especially Escherichia coli, has impacted recommendations for empiric antimicrobial therapy, and fluoroquinolones have emerged as the empiric therapy of choice for individuals managed as outpatients; more options are available for empiric parenteral therapy for those who require hospitalization . Further study of the epidemiology of antimicrobial resistance among uropathogens and of alternative agents for the management of pyelonephritis is urgently needed. Postgrad Med J, 2004 Nov, 80(949), 660 - 2 Avoiding laboratory pitfalls in infectious diseases; Lo TS et al.; In today's medical care environment, clinicians are challenged to order clinically relevant, cost effective laboratory tests and antibiotic therapy . Together, physicians and laboratories must have guidelines and strategies that can provide quality patient care, while minimising costs and preventing further emergence of antimicrobial drug resistance . Five clinical vignettes that demonstrate these principles are presented. J Pharmacol Exp Ther . 2004 Nov 10; {Epub ahead of print} Glabridin, an isoflavan from licorice root, inhibits inducible nitric oxide synthase expression and improves survival of mice in experimental model of septic shock; Kang JS et al.; Glabridin, a flavonoid present in licorice extract, is known to have antimicrobial, anti-inflammatory and cardiovascular protective activities . In the present study, we report the inhibitory effect of glabridin on nitric oxide (NO) production and inducible nitric oxide (iNOS) gene expression in murine macrophages . Glabridin attenuated lipopolysaccharide (LPS)-induced NO production in isolated mouse peritoneal macrophages and RAW 264.7 cells, a mouse macrophage-like cell line . Moreover, iNOS mRNA expression was also blocked by glabridin treatment in LPS-stimulated RAW 264.7 cells . Further study demonstrated that the LPS-induced NF-& {kappa}B/Rel DNA binding activity and NF-kappaB/Rel- dependent reporter gene activity were significantly inhibited by glabridin in RAW 264.7 cells and that this effect was mediated through the inhibition of inhibitory factor-kappaB degradation and p65 nuclear translocation . Moreover, reactive oxygen species generation was also suppressed by glabridin treatment in RAW 264.7 cells . In contrast, the activity of mitogen- activated protein kinases was unaffected by glabridin treatment . In animal model, in vivo administration of glabridin increased the rate of survival of LPS-treated mice and inhibited LPS-induced increase in plasma concentrations of nitrite/nitrate and tumor necrosis factor-alpha . Collectively, these data suggest that glabridin inhibits NO production and iNOS gene expression by blocking NF-kappaB/Rel activation and that this effect was mediated, at least in part, by inhibiting reactive oxygen species generation . Furthermore, in vivo anti-inflammatory effect of glabridin suggests a possible therapeutic application of this agent in inflammatory diseases. J Antimicrob Chemother, 2004 Dec, 54(6), 1019 - 24 Epub 2004 Nov 10. Silver nanoparticles and polymeric medical devices: a new approach to prevention of infection? Furno F, Morley KS, Wong B, Sharp BL, Arnold PL, Howdle SM, Bayston R, Brown PD, Winship PD, Reid HJ. OBJECTIVES: Implantable devices are major risk factors for hospital-acquired infection . Biomaterials coated with silver oxide or silver alloy have all been used in attempts to reduce infection, in most cases with controversial or disappointing clinical results . We have developed a completely new approach using supercritical carbon dioxide to impregnate silicone with nanoparticulate silver metal . This study aimed to evaluate the impregnated polymer for antimicrobial activity . METHODS: After impregnation the nature of the impregnation was determined by transmission electron microscopy . Two series of polymer discs were then tested, one washed in deionized water and the other unwashed . In each series, half of the discs were coated with a plasma protein conditioning film . The serial plate transfer test was used as a screen for persisting activity . Bacterial adherence to the polymers and the rate of kill, and effect on planktonic bacteria were measured by chemiluminescence and viable counts . Release rates of silver ions from the polymers in the presence and absence of plasma was measured using inductively coupled plasma mass spectrometry (ICP-MS) . RESULTS: Tests for antimicrobial activity under various conditions showed mixed results, explained by the modes and rates of release of silver ions . While washing removed much of the initial activity there was continued release of silver ions . Unexpectedly, this was not blocked by conditioning film . CONCLUSIONS: The methodology allows for the first time silver impregnation (as opposed to coating) of medical polymers and promises to lead to an antimicrobial biomaterial whose activity is not restricted by increasing antibiotic resistance. J Antimicrob Chemother, 2004 Dec, 54(6), 1109 - 15 Epub 2004 Nov 10. Reduced colonization and infection with miconazole-rifampicin modified central venous catheters: a randomized controlled clinical trial; Yucel N et al.; OBJECTIVE: Central venous catheters (CVC) are a major cause of nosocomial bloodstream infections . Catheters modified with miconazole and rifampicin that constantly and slowly release antimicrobial substances are assumed to be beneficial in reducing rates of colonization and catheter-related infections . Design and setting: Prospective controlled non-blinded randomized clinical trial in two German university hospitals . Patients: 223 adult inpatients with CVC between October 2000 and February 2002 . Baseline characteristics, APACHE II score and therapeutic interventions were comparable . Intervention: Randomization to receive either a miconazole and rifampicin modified catheter (n=118) or a standard triple-lumen CVC (n=105) . Measurements, definitions: Microbiological evaluation was done after CVC removal . A catheter was considered colonized if growth of >/=15 cfu was found by semi-quantitative roll-plate technique from a proximal or distal catheter segment . A catheter-related infection (CRI) was defined as a colonized catheter with local signs of inflammation . A catheter-related bloodstream infection (CR-BSI) was defined as a colonized catheter with isolation of the same organism from the patient's blood with accompanying clinical signs of infection . RESULTS: A colonization of CVC was observed in six patients (5.1%) with a modified catheter and 38 patients (36.2%) with a standard catheter (P < 0.001) . Five patients in the modified group (4.2%) and 18 in the standard group (17.1%) developed CRI (P=0.002) . One assumed CR-BSI was detected in the standard group, with none in the modified group . No adverse effects related to the modified catheters and no antimicrobial resistance were observed . CONCLUSION: CVC supersaturated with miconazole and rifampicin were associated with a significantly lower risk for catheter colonization and catheter-related infections compared to standard catheters. J Antimicrob Chemother, 2004 Dec, 54(6), 1122 - 6 Epub 2004 Nov 10. Increase and change in pattern of hospital antimicrobial use, Denmark, 1997-2001; Muller-Pebody B et al.; OBJECTIVES: To analyse the changes and compare antimicrobial consumption in public hospitals in Denmark over the period 1997-2001 . METHODS: Data on the number of WHO defined daily doses (DDD) were obtained from the Danish Medicines Agency . Data on the number of bed-days were obtained from the National Board of Health . We calculated antimicrobial consumption in hospitals as the number of DDD per 100 bed-days for all antibacterials for systemic use i.e . group J01 of the Anatomical Therapeutic Chemical (ATC) classification and for classes of this group . RESULTS: During 1997-2001, antimicrobial use in hospitals in Denmark significantly increased by 18%, from 38.0 to 44.8 DDD per 100 bed-days (P < 0.005) . Most of this increase (55%) was attributed to an increase in consumption of commonly used classes of antimicrobials, mainly penicillins with extended spectrum (ATC group J01CA), beta-lactamase-sensitive penicillins (J01CE) and beta-lactamase-resistant penicillins (J01CF) . The 'broad-spectrum' and newer antimicrobials, i.e . combinations of penicillins with beta-lactamase inhibitor (J01CR), cephalosporins (J01DA), carbapenems (J01DH) and fluoroquinolones (J01MA) contributed to 36% of the increase . Together, these amounted to 16% of total consumption in hospitals in Denmark in 1997, rising to 19% in 2001 . CONCLUSIONS: Although antimicrobial consumption in public hospitals in Denmark is low compared with other countries, the steady increase and change in pattern of their use are causes of concern, deserving close monitoring and further investigations. J Agric Food Chem, 2004 Nov 17, 52(23), 6932 - 8 Evaluation of the antimicrobial activity of citrus essences on Saccharomyces cerevisiae; Belletti N et al.; The aim of this research was to assess the antimicrobial activity of nine different industrial essences used in a soft drink factory in relation to their composition, as well as to verify the role of vapor pressure on their bioactivity . The essences were tested against a Saccharomyces cerevisiae strain isolated from spoiled soft drinks . The tests were carried out by adding the essences directly to a liquid medium or into the headspace of closed systems inoculated with the yeast . The headspace composition was evaluated through a solid phase microextraction-gas chromatography technique . The use of a mass spectrometer allowed the identification of the peaks detected . The microbial growth was indirectly monitored by measuring the metabolic CO2 released by the yeast . The results obtained indicated that the most effective essences were characterized by the highest concentration of some terpenes, such as citral, beta-pinene, and p-cymene . Moreover, all of the essences were more bioactive when added directly to the liquid medium. J Int Acad Periodontol, 2004 Oct, 6(4 Suppl), 154 - 9 Treatment of incipient peri-implant infections using topical minocycline microspheres versus topical chlorhexidine gel as an adjunct to mechanical debridement; Renvert S et al.; This report presents the clinical results three months after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared to adjunctive treatment employing 1% chlorhexidine gel application . Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study . Each patient had one or more implants with probing depth > or = 4 mm combined with bleeding and/or exudate on probing and presence of putative pathogenic bacteria . At baseline, patients were randomly assigned to minocycline or chlorhexidine treatment . Follow-up examinations were carried out after 10, 30, 60 and 90 days . The combined mechanical/antimicrobial treatment for the chlorhexidine group did not result in any reduction in probing depth and only limited reduction of bleeding scores . The adjunctive use of minocycline microspheres, on the other hand, resulted in improvements in both probing depths and bleeding scores . For the deepest sites of the treated implants, mean probing depth was reduced from 5.0 mm to 4.1 mm . The reductions in bleeding scores, although greater than for the chlorhexidine group, were modest . Thus, the question as to what extent the combined mechanical/minocycline treatment could be considered adequate for the treated lesions remains to be answered . The present short-term findings, however, encourage further studies with longer observation intervals on adjunctive use of minocycline microspheres in the treatment of periimplant lesions. Genome Biol . 2004;5(11):R93 . Epub 2004 Nov 01. How biologically relevant are interaction-based modules in protein networks? Poyatos JF, Hurst LD. By applying a graph-based algorithm to yeast protein-interaction networks we have extracted modular structures and show that they can be validated using information from the phylogenetic conservation of the network components . We show that the module cores, the parts with the highest intramodular connectivity, are biologically relevant components of the networks . These constituents correlate only weakly with other levels of organization . We also discuss how such structures could be used for finding targets for antimicrobial drugs. Eur J Gen Pract, 2004 Sep, 10(3), 88 - 92 Spanish primary healthcare physicians' knowledge of resistance of respiratory germs and antimicrobial treatment in acute bronchitis; Llor C et al.; OBJECTIVES: To determine what Spanish primary healthcare physicians consider the rates of pneumococcal resistance to be, the type of antimicrobial treatment they would prescribe on suspicion of high resistance and ascertain in which cases of acute bronchitis these physicians would initiate antibiotic treatment . METHODS: A cross-sectional, observational study was performed with a questionnaire distributed to 1368 physicians on their opinion on the degree of resistance of pneumococci to penicillins and macrolides in Spain . They were also asked which treatment they would recommend in penicillin-resistant pneumococcal infection and to indicate their degree of agreement regarding the use of antibiotics in different clinical situations of acute bronchitis . RESULTS: 843 physicians completed and returned the questionnaire, a response rate of 59.1% . Of the 750 physicians who answered the question concerning pneumococcal resistance, 312 stated resistance to be >30% (41.6%) while only 90 felt it to be <15% (12%) . 153 physicians reported resistance to macrolides to be >30% (23%) . In cases with suspicion of penicillin-resistant pneumococci, the clinicians stated they would prescribe quinolones (321, 40.3%) and macrolides (251, 31.5%) . Of the 784 physicians who answered the questions on bronchitis, 662 preferred antibiotic therapy in acute bronchitis with purulent sputum (84.6%), 610 on uncertain diagnosis (77.8%), 569 in patients with fever over 38 degrees C (72.6%) and 210 on patient request (26.8%) . CONCLUSION: Primary healthcare physicians in Spain are more concerned about pneumococcal resistance to penicillins than to macrolides although 35% of the strains isolated are resistant to the latter while only 10% are resistant to aminopenicillins . Furthermore, many physicians believe macrolides to be effective against pneumococcal infections . Despite their lack of efficacy in the treatment of acute bronchitis, many physicians prescribe antibiotics, mainly in cases with purulent expectoration, thus justifying the high consumption of antimicrobial agents in this disease. Med Hypotheses, 2005, 64(1), 14 - 6 Antibiotics may act as growth/obesity promoters in humans as an inadvertent result of antibiotic pollution? Ternak G. The growth promoting effects of antibiotics were first discovered in the 1940s . Since then, many antimicrobials have been found to improve average daily weight gain and feed efficiency . The total production of antibiotics can be estimated between 100,000-200,000 tons annually and the human population is being influenced, directly or indirectly (from the environment) by this amount of drug . The twentieth-century increase in human height and the obesity of the population is roughly observed since the mass consumption of antibiotics 40-50 years ago . The association between antibiotic consumption and the increase of human growth/obesity is suspected. Oral Dis, 2004 Nov, 10(6), 389 - 97 Molecular evaluation of residual endodontic microorganisms after instrumentation, irrigation and medication with either calcium hydroxide or Septomixine; Tang G et al.; BACKGROUND AND OBJECTIVE: The correct choice of antimicrobial agents as inter-appointment medicaments is as important as the instrumentation and irrigation to remove pathogens from infected root canals . Calcium hydroxide {Ca(OH)2} and framycetin sulfate (Septomixine) are common endodontic medicaments . Therefore, we evaluated the efficacy of either calcium hydroxide or Septomixine in eliminating residual intra-canal bacteria, particularly Actinomyces spp., during inter-appointment interval in endodontic therapy using molecular methods . METHODS: A total of 31 single-rooted teeth with primary root canal infections were studied immediately after opening the canals and subsequently after instrumentation, irrigation with sterile saline and 1-week medication with either Ca(OH)2 (n = 25) or Septomixine (n = 6) . Whole bacterial genomic DNA was isolated directly from samples and PCR with universal primers performed to detect total intra-canal bacteria . The variable regions of 16S rDNA of bacteria were amplified and labeled with digoxigenin for further hybridization to detect Actinomyces spp . A total of seven oligonucleotide probes specific for A . bovis, A . gerencseriae, A . israelii, A . meyeri, catalase-negative A . naeslundii (genospecies 1 and 2), catalase-positive A . naeslundii genospecies 2 and A . odontolyticus were used to detect Actinomyces spp . in 22 of 31 medicated root canals {Ca(OH)2: n = 17; Septomixine: n = 5} . RESULTS: The PCR results showed that 25 of 31 examined canals were positively detected with residual microorganisms after instrumentation, irrigation with sterile saline and 1-week medication with either Ca(OH)2 (n = 20) or Septomixine (n = 5) . Thus, only six canals {Ca(OH)2: n = 5, Septomixine: n = 1} were aseptic after treatment . Hybridization results showed higher detection frequency of both A . odontolyticus and A . gerencseriae after treatment . Significant correlation was found between exposed pulp before treatment and positive detection of Actinomyces spp., particularly A . odontolyticus on the second visit (P < 0.05) . CONCLUSION: The conventional, 1-week medication of either Ca(OH)2 or Septomixine in endodontic therapy may not effectively inhibit residual bacterial growth in all root canals during inter-appointment intervals . Further investigations using, for instance quantitative real-time PCR analyses, are required to substantiate the present findings. Clin Otolaryngol, 2004 Dec, 29(6), 725 - 8 Guidelines for the management of periorbital cellulitis/abscess; Howe L et al.; Orbital and periorbital swelling secondary to acute sinusitis is relatively common . Distinguishing between preseptal and orbital involvement can be difficult based on clinical observations alone . A delay in diagnosis and appropriate treatment may result in serious complications including blindness . The literature is reviewed and simple guidelines suggested to manage such patients, including their initial assessment, investigations with particular reference to the indications and timing of CT scanning, antimicrobial therapy and the type of surgery . These guidelines have been approved across disciplines in our unit and trialled successfully for 2 years. Can Vet J, 2004 Oct, 45(10), 849 - 51 Phosphate enema toxicosis in a pygmy goat wether; Hickman SA et al.; Phosphate enema toxicity was diagnosed in a 7-month-old, castrated male, pygmy goat . On presentation, clinical findings included mild depression, tachycardia, tachypnea, rumen stasis, muscle tremors, hypocalcemia, hypokalemia, hypochloremia, hyperphosphatemia, azotemia, and metabolic acidosis . Fluid diuresis and parenteral antimicrobial therapy resulted in recovery after 3 d of treatment. Probl Tuberk Bolezn Legk, 2004, (9), 42 - 5 {Antimicrobial activity of blood phagocytes in patients with tuberculosis and respiratory sarcoidosis}; Comparative efficacy of enrofloxacin et al.; Department of Avian Medicine, The University of Georgia, Athens, GA 30602, USAThe purpose of the present study was to compare the ability of enrofloxacin, oxytetracycline, and sulfadimethoxine to reduce morbidity and mortality caused by Escherichia coli (colibacillosis) in broiler chickens . The chickens were raised in 80 pens (20 birds per pen) with 20 pens representing each treatment group under simulated commercial conditions that produced a colibacillosis challenge scenario . Each group of 20 randomized pens (replicates) was given one of four water treatments . Chickens that received enrofloxacin had significantly less mortality (P < 0.01), lower average gross pathology (colibacillosis) scores (P < 0.01), and better feed-conversion ratios (P < 0.05) than did chickens that received either oxytetracycline or no medication . Chickens that received enrofloxacin had significantly less mortality and lower pathology scores than those that received sulfadimethoxine and numerically lower feed conversion than the sulfadimethoxine group . Results from the present study show that enrofloxacin is superior to oxytetracycline and sulfadimethoxine for the control of morbidity and mortality caused by E . coli in broiler chickens . Our findings will help veterinarians choose and prescribe the most efficacious antimicrobial when treating colibacillosis. Arthritis Rheum, 2004 Nov, 50(11), 3526 - 34 Production of endogenous antibiotics in articular cartilage; Varoga D et al.; OBJECTIVE: Defensins are broad-spectrum antimicrobial peptides that are components of innate immunity . To date, only epithelial surfaces and blood cells have been shown to produce these cationic peptides in bactericidal concentrations when challenged with microorganisms or inflammatory cytokines . Infections caused by gram-negative pathogens occur only infrequently in association with joint surgery . The present study was undertaken to investigate whether this may be explained by intraarticular production of gram-negative-specialized antimicrobial peptides . METHODS: Healthy articular cartilage and cultured T/C-28a2 chondrocytes were assessed, by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, for expression of various antimicrobial peptides . The expression of human beta-defensin 2 (HBD-2) was studied in cultured chondrocytes after exposure to bacterial supernatants and proinflammatory cytokines and was assayed by real-time RT-PCR and immunoblot analysis . A septic arthritis mouse model was used to investigate the regulation of the murine homolog of HBD-2 in articular cartilage after bacterial inoculation . RESULTS: Healthy articular cartilage and T/C-28a2 chondrocytes were able to produce different antimicrobial peptides . After exposure to gram-negative bacteria and proinflammatory cytokines, expression of cartilage-derived HBD-2 strongly increased . Immunoblot analysis revealed up-regulation of the gram-negative-specialized HBD-2 in microbicidal doses . Immunohistochemistry analysis revealed induction of the murine homolog of HBD-2 in vivo after intraarticular injection of bacteria . CONCLUSION: This study demonstrated a previously unrecognized function of human chondrocytes . In addition to its biomechanical properties, articular cartilage has the ability to produce antimicrobial substances when challenged with microorganisms . The expression of HBD-2 in microbicidal doses suggests that antimicrobial peptides may contribute to host defense mechanisms in articular joints. J Immunol, 2004 Nov 15, 173(10), 6134 - 42 Human ribonuclease A superfamily members, eosinophil-derived neurotoxin and pancreatic ribonuclease, induce dendritic cell maturation and activation; Yang D et al.; A number of mammalian antimicrobial proteins produced by neutrophils and cells of epithelial origin have chemotactic and activating effects on host cells, including cells of the immune system . Eosinophil granules contain an antimicrobial protein known as eosinophil-derived neurotoxin (EDN), which belongs to the RNase A superfamily . EDN has antiviral and chemotactic activities in vitro . In this study, we show that EDN, and to a lesser extent human pancreatic RNase (hPR), another RNase A superfamily member, activates human dendritic cells (DCs), leading to the production of a variety of inflammatory cytokines, chemokines, growth factors, and soluble receptors . Human angiogenin, a RNase evolutionarily more distant to EDN and hPR, did not display such activating effects . Additionally, EDN and hPR also induced phenotypic and functional maturation DCs . These RNases were as efficacious as TNF-alpha, but induced a different set of cytokine mediators . Furthermore, EDN production by human macrophages could be induced by proinflammatory stimuli . The results reveal the DC-activating activity of EDN and hPR and suggest that they are likely participants of inflammatory and immune responses . A number of endogenous mediators in addition to EDN have been reported to have both chemotactic and activating effects on APCs, and can thus amplify innate and Ag-specific immune responses to danger signals . We therefore propose these mediators be considered as endogenous multifunctional immune alarmins. Int J Food Microbiol, 2004 Dec 1, 97(1), 81 - 4 Isolation of shiga toxigenic Escherichia coli from raw beef in Palestine; Adwan GM et al.; Shiga toxigenic Escherichia coli (STEC) isolated from raw beef samples in northern Palestine during a 1-year period were characterized for virulence genes by a polymerase chain reaction (PCR) assay and screened for their antibiotic resistance . STEC was identified in 44 (14.7%) of 300 raw beef samples . Twelve (27.3%) of the STEC isolates were serotype O157 . Nine of those were isolated during summer . The majority of STEC isolates (70.5%) harbored both stx1 and stx2 genes, while the others harbored either stx1 or stx2 . High levels of resistance against different antimicrobial agents were detected . Resistance to at least three drugs was found in 55% of the isolates. FEBS Lett, 2004 Nov 5, 577(1-2), 209 - 14 Purification and primary structure of two isoforms of arenicin, a novel antimicrobial peptide from marine polychaeta Arenicola marina; Ovchinnikova TV et al.; Two novel 21-residue antimicrobial peptides, arenicin-1 and arenicin-2, exhibiting activity against Gram-positive and Gram-negative bacteria and fungi, were purified from coelomocytes of marine polychaeta Arenicola marina (lugworm) by preparative gel electrophoresis and RP-HPLC . Molecular masses (2758.3 and 2772.3 Da) and complete amino acid sequences (RWCVYAYVRVRGVLVRYRRCW and RWCVYAYVRIRGVLVRYRRCW) were determined for each isoform . Each arenicin has one disulfide bond (Cys3-Cys20) . The total RNA was isolated from the lugworm coelomocytes, RT-PCR and cloning were performed, and cDNA was sequenced . A 202-residue preproarenicin contains a putative signal peptide (25 amino acids) and a long prodomain . Arenicins have no structure similarity to any previously identified antimicrobial peptides. J Org Chem, 2004 Nov 12, 69(23), 7851 - 9 A practical synthesis of gramicidin s and sugar amino Acid containing analogues; Grotenbreg GM et al.; A practical gram-scale and high-yielding synthesis of the antimicrobial peptide gramicidin S is presented . An Fmoc-based solid-phase peptide synthesis protocol is employed for the generation of the linear decapeptide precursor, which is cyclized in solution to afford the target compound . The versatility of our method is demonstrated by the construction of eight gramicidin S analogues (15a-h) having nonproteinogenic sugar amino acid residues (4-7) incorporated in the turn regions. Proteomics, 2004 Dec, 4(12), 3953 - 9 Characterization of the in vivo forms of lacrimal-specific proline-rich proteins in human tear fluid; Fung KY et al.; The tear film is complex and is rich in both peptides and proteins . Physiological factors have been shown to alter the balance of the protein components in the tear film, however, little is known of the precise stimuli that initiate these changes, or their nature and extent . Attention has been directed at the role of tear proteins in the protection of the external ocular surface, and their potential role in the pathogenesis of inflammatory and autoimmune diseases, but few lacrimal-specific proteins have been identified and demonstrated to offer a protective function at the ocular surface . The biological importance of proline-rich proteins is uncertain, although there is some evidence to indicate a potential antimicrobial function for these proteins in saliva . Despite the detection of mRNA for proline-rich proteins in lacrimal gland, the translated protein product has not been detected in tear fluid . In this study we investigate the presence of proline-rich proteins in the tear film . Human reflex tear fluid was examined by matrix-assisted laser desorption/ionization-time of flight mass spectrometry directly, and following size exclusion high performance liquid chromatography . This revealed significant levels of a truncated form of lacrimal proline-rich protein, and a series of peptides derived the C-terminus of this protein . None of these had previously been identified in tear . Our study highlights the dangers inherent in proteomic strategies that assign an identity to a protein based on limited coverage of tryptic peptides. J Vet Med B Infect Dis Vet Public Health, 2004 Oct-Nov, 51(8-9), 419 - 21 Antimicrobial resistance in bacteria from food-producing animals . risk management tools and strategies; Grugel C et al.; The application of antimicrobial agents has proved to be the main risk factor for development, selection and spread of antimicrobial resistance . This link applies to the use of antimicrobial agents in human and in veterinary medicine . Furthermore, antimicrobial-resistant bacteria and resistant genes can be transmitted from animals to humans either by direct contact or via the food chain . In this context, risk management has to be discussed regarding prevention and control of the already existing antimicrobial resistance . One of the primary risk management measures in order to control the development and spread of antimicrobial resistances is by regulating the use of antimicrobial agents and subjecting their use to guidelines . Thereby, the occurrence of antimicrobial resistant bacteria in the human and veterinary habitat can be controlled to a certain degree . There is little information about past attempts to prevent the development of resistances or to control them, and even less is known about the effectiveness or the cost intensiveness of such efforts . Most of the strategies focus on preventing and controlling antimicrobial resistance by means of the reduction or limitation of the use of antimicrobial agents in food-producing animals. J Vet Med B Infect Dis Vet Public Health, 2004 Oct-Nov, 51(8-9), 415 - 8 Developing new regulatory approaches to antimicrobial safety; Tollefson L; Resistance to antimicrobial agents is of concern to public health officials worldwide . In industrialized countries, a significant source of antimicrobial-resistant food-borne infections in humans is the acquisition of resistant bacteria originating from animals . The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals . The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals . Recently the FDA published a guidance document titled 'Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern' (US Food and Drug Administration, Center for Veterinary Medicine, 2003) . This document outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug . The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans . The level of risk determines the level of risk management that is required for the drug to be used . The Food and Drug Administration (FDA) always has the option of not approving a drug if the risk of a public health consequence is too high. J Vet Med B Infect Dis Vet Public Health, 2004 Oct-Nov, 51(8-9), 403 - 7 Conclusions and activities of previous expert groups: the Scientific Steering Committee of the EU; Fries R; In 1998, the EU Commission consulted its Scientific Steering Committee (SSC) to give advice on actions against anti-microbial resistance based on scientific evidence . The SSC set up a working group and adopted in 1999 an Opinion on Antimicrobial Resistance . Statements given in the well-structured document are clear, and precise recommendations were proposed . Summarizing, the Committee stated: There is evidence to suppose a continuous flow of resistance genes between pathogenic and commensal bacteria and of transfer of these bacteria between different compartments of the biosphere, thus changing the genetic resources continuously . There exist numerous factors which influence the emergence and spread of anti-bacterial resistance . However, it is likely that restriction in the use of anti-microbials will lead to a containment or a reduction of the drug resistance problem . Actions should be taken promptly to reduce the overall use of anti-microbials in a balanced way in all areas: human medicine, veterinary medicine, animal production and plant protection. J Vet Med B Infect Dis Vet Public Health, 2004 Oct-Nov, 51(8-9), 380 - 8 Monitoring of antimicrobial resistance among food animals: principles and limitations; Aarestrup FM; Large amounts of antimicrobial agents are in the production of food animals used for therapy and prophylactics of bacterial infections and in feed to promote growth . The use of antimicrobial agents causes problems in the therapy of infections through the selection for resistance among bacteria pathogenic for animals or humans . Current knowledge regarding the occurrence of antimicrobial resistance in food animals, the quantitative impact of the use of different antimicrobial agents on selection for resistance and the most appropriate treatment regimes to limit the development of resistance is incomplete . Programmes monitoring the occurrence and development of resistance are essential to determine the most important areas for intervention and to monitor the effects of interventions . When designing a monitoring programme it is important to decide on the purpose of the programme . Thus, there are major differences between programmes designed to detect changes in a national population, individual herds or groups of animals . In addition, programmes have to be designed differently according to whether the aim is to determine changes in resistance for all antimicrobial agents or only the antimicrobial agents considered most important in relation to treatment of humans . In 1995 a continuous surveillance for antimicrobial resistance among bacteria isolated from food animals was established in Denmark . Three categories of bacteria, indicator bacteria, zoonotic bacteria and animal pathogens are continuously isolated from broilers, cattle and pigs and tested for susceptibility to antimicrobial agents used for therapy and growth promotion by disc diffusion or minimal inhibitory concentration determinations . This programme will only detect changes on a national level . However, isolating the bacteria and testing for several antimicrobial agents will enable us to determine the effect of linkage of resistance . Since 1995 major differences in the consumption pattern of different antimicrobial agents have occurred in Denmark . The Danish monitoring programme has enabled us to determine the effect of these changes on the occurrence of resistance . The Danish monitoring is, however, not suited to determine changes on a herd level or to detect emergence of new types of resistance only occurring at a low level. Pol Merkuriusz Lek, 2004 May, 16 Suppl 1, 88 - 90 {Immunomodulating properties of antibiotics}; Targowski T; Antimicrobial agents are typically regarded as an exogenous factor responsible only for killing pathogens . However we have more and more data that numerous antibiotics have modulating influence on immunological system, not directly associated with bacteriostatic or bactericidal properties of those antibiotics . The review presents current knowledge about this issue. Insect Biochem Mol Biol, 2004 Nov, 34(11), 1163 - 73 TsetseEP, a gut protein from the tsetse Glossina morsitans, is related to a major surface glycoprotein of trypanosomes transmitted by the fly and to the products of a Drosophila gene family; Chandra M et al.; African trypanosomes live in the lumen of the gut of tsetse (Glossina) and may have to face an immune response . As yet, it is unclear whether they are sensitive to antimicrobial peptides in vivo, but for some years there has been indirect evidence that one or more lectins can influence the infection . We have purified a protein complex from midgut extracts that, by SDS-PAGE, is a doublet of 37 and 38 kDa in a ratio of 3:1 . Through prediction from corresponding cDNA clones, the full-length protein (tsetseEP) contains 320 amino acids, including a signal peptide . There is apparently only one gene encoding this protein . Towards the C terminus, the protein contains a run of 59 (EP) repeats, which surprisingly is what comprises almost the entire mature EP procyclin molecule present on the surface of trypanosomes in the tsetse gut . Drosophila contains a number of genes encoding proteins, of unknown function, with the same cysteine pattern as tsetseEP; this pattern is not reported for any other protein . Immunoblotting with a monoclonal antibody against (EP) repeats reveals expression in the gut, but not salivary glands, of female and male flies, whether or not fed . Immunoelectron microscopy shows the presence in vesicles in midgut cells and in the lumen of the gut . Attempts to demonstrate lectin activity were thwarted by limited availability of the protein complex. J Inorg Biochem, 2004 Nov, 98(11), 1712 - 21 Biologically relevant tetraazamacrocyclic complexes of manganese: synthetic, spectral, antimicrobial, antifertility and antiinflammatory approach; Singh RV et al.; The testicular sperm density, sperm morphology, sperm motility, density of cauda epididymis spermatozoa and fertility in mating trials and biochemical parameters of reproductive organs have been examined and discussed for {Mn(N(4)MacL(n))(NO(3))(2)} (where N(4)MacL(n) represents the tetraazamacrocyclic ligand molecule with n=1-4) type of complexes . An attempt also has been made to correlate the structural aspects of the compounds with their anti-inflammatory activity . The 14-18 membered tetraamide macrocyclic ligands N(4)L(1)-N(4)L(4) used during these investigations have been prepared by the condensation of 1,2-diaminoethane or 1,3-diaminopropane with malonic or succinic acid in the presence of condensing reagents, dicyclohexylcarbodiimide and 4-dimethylaminopyridine . On reduction, these macrocyclic ligands give a new series of tetraazamacrocyles {N(4)MacL(n)} and their complexes with manganese(II) nitrate . The ligands and their complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, mass and X-ray structural analyses . An octahedral geometry for these complexes has been confirmed by spectral studies . On the basis of the chemical composition, the representation of the complexes as {Mn(N(4)MacL(n))(NO(3))(2)} has been established . The ligands and their complexes have been screened in vitro against a number of pathogenic fungi and bacteria to assess their growth inhibiting potential. Clin Microbiol Infect, 2004 Nov, 10 Suppl 4, 23 - 31 Antimicrobial drug development--the past, the present, and the future; Powers JH; Antimicrobial resistance has been an issue since the introduction into clinical use of the first agents in the 1940s . Although the discovery and development of new classes of antimicrobials through the 1960s presented an array of treatment options, these options for some serious and life-threatening infectious diseases may now be more limited . This paper examines the history of antimicrobial development, showing how the challenges in discovering new classes of drugs have been with us for the last 40 years . The present state of antimicrobial discovery and development is shaped by these challenges as well as by the economic realities of the pharmaceutical industry . This paper also discusses some of the regulatory considerations in antimicrobial drug development, and presents some potential solutions to the challenges inherent in antimicrobial drug development, including steps taken by the US Food and Drug Administration to streamline the drug review process for antimicrobial agents while maintaining the standards necessary to protect and promote the health of the public. Clin Microbiol Infect, 2004 Nov, 10(11), 990 - 8 Relationship between pharmacokinetics and pharmacodynamics of beta-lactams and outcome; Sadaba B et al.; The in-vitro susceptibility of an organism and the pharmacokinetics of an antimicrobial agent are two basic factors on which the choice of standardised treatment regimens is based . However, the inter-individual variability of these factors, which modifies the exposure of bacteria to an antibiotic in terms of time and quantity, is not usually taken into account . In 87 patients treated with beta-lactams (ceftriaxone, cefepime or piperacillin), the probability of failure was greater when the infectious process was located in tissues with barriers to the distribution of beta-lactams . Mean MICs of piperacillin and cefepime, but not ceftriaxone, were below the breakpoints in cases of both recovery and failure, but organisms isolated from patients with a poor outcome had higher MICs . Therefore, the use of breakpoints to determine the susceptibility of microorganisms was not satisfactory in predicting the outcome for a large number of patients . If MICs are determined and plasma concentrations are monitored, dosages can be adjusted according to these parameters, thereby allowing antibiotic treatment to be individualised. Mamm Genome, 2004 Oct, 15(10), 834 - 42 Bovine beta-defensins: identification and characterization of novel bovine beta-defensin genes and their expression in mammary gland tissue; Roosen S et al.; beta-Defensin genes code for multifunctional peptides with a broad-range antimicrobial activity . In this project we hypothesized that beta-defensin genes may be candidate genes for resistance to mastitis . In this article we describe the identification and genomic characterization of eight bovine beta-defensin genes, including six novel defensin genes and two pseudogenes . Expression in the bovine mammary gland of one of the novel genes, DEFB401, has been demonstrated, as well as the expression of LAP, TAP, DEFB1, BNBD3, BNBD9, and BNBD12 . For genomic characterization, 20 BACs from two different bovine BAC libraries (RZPD numbers 750 and 754) were isolated by PCR screening with beta-defensin consensus primers derived from published sequences . PCR products from BACs generated with consensus primers have been subcloned and sequenced, revealing a total of 16 genes and two pseudogenes . Six novel beta-defensin genes share the typical exon-intron structure and are highly homologous to published bovine beta-defensin genes . They are named DEFB401- DEFB405 and LAP-like, and two novel pseudogenes are named EBD-P and EBD-P2 . Analysis of mammary gland tissue-derived cDNA from nine cows with different clinical findings demonstrated the expression of several beta-defensin genes mentioned above . First results indicate that the lactational status of the cow presumably has no influence on gene expression . Competent knowledge of antimicrobial activity of beta-defensins from literature, the abundance of beta-defensin mRNA in the bovine mammary gland, and the inducibility of some genes give first evidence that beta-defensins may play a role in local host defense during udder infections. Int J Antimicrob Agents, 2004 Nov, 24(5), 491 - 5 Taurolidine is effective in the treatment of central venous catheter-related bloodstream infections in cancer patients; Koldehoff M et al.; Taurolidine is an antimicrobial agent that was originally used in the local treatment of peritonitis and was shown to be effective in the prevention of catheter-related bloodstream infections (CR-BSI) . In this pilot study, we used taurolidine solution as an intravenous (i.v.) lock into the totally implantable intravascular devices of 11 consecutive oncological patients with catheter-related bloodstream infections not responding to systemic antimicrobial chemotherapy . All patients recovered completely from the infection . No adverse drug effects were seen . Three patients were successfully retreated for a recurrent infection . Our data suggest a beneficial role of taurolidine i.v . lock for the therapy of catheter-related bloodstream infections in oncological patients . Taurolidine i.v . lock application is feasible and could especially be useful in infections resistant to antibiotic chemotherapy. Int J Antimicrob Agents, 2004 Nov, 24(5), 463 - 7 Impact of antimicrobial exposure and beta-lactamase-producing bacteria on salivary beta-lactamase activity in infancy; Nyfors S et al.; Beta-lactamase production by oral bacteria is common in infancy and is associated with use of antimicrobial agents in infants . The present longitudinal study aimed to examine the frequency of salivary beta-lactamase activity (SbetaA), to compare SbetaA with the presence of beta-lactamase-producing (beta+) aerobic and anaerobic species in saliva, and to estimate the impact of antimicrobial exposure on the emergence of SbetaA in healthy infants during their first year of life . At 6 months, SbetaA was detected in 46% infants; 89% SbetaA-positive infants and 55% SbetaA-negative infants harboured beta+ species at this time (OR 7.08; CI 1.31-38.34) . At 12 months, SbetaA was detected in 54% infants . Exposure to antimicrobials during the first year of life increased the risk (OR 2.60; CI 0.72-9.36) of having SbetaA. Int J Antimicrob Agents, 2004 Nov, 24(5), 433 - 8 High levels of dual resistance to clarithromycin and metronidazole and in vitro activity of levofloxacin against Helicobacter pylori isolates from patients after failure of therapy; Branca G et al.; Current treatment for Helicobacter pylori infections generally includes two or more antimicrobials (amoxicillin, clarithromycin, nitroimidazoles, tetracycline, etc.), but treatment fails in 10-20% of all cases, often because of drug resistance . Levofloxacin has been proposed as an alternative for these refractory infections . We examined 67 H . pylori isolates from patients unsuccessfully treated with amoxicillin, clarithromycin, metronidazole and levofloxacin . Minimum inhibitory concentrations determined with the epsilometer test revealed clarithromycin and metronidazole resistance in 91 and 82.1% of the isolates, respectively; 52 (77.6%) were resistant to both drugs . All 67 isolates were susceptible to amoxicillin and tetracycline . Fifty-two isolates had levofloxacin MICs of 0.01-2 mg/l; the remaining 15 (22.4%), all clarithromycin- and metronidazole-resistant, had MICs >/= 8 mg/l . Levofloxacin may be an option for refractory H . pylori infections, but the choice should be based on in vitro susceptibility data, and physicians should consider local resistance patterns when treating these infections empirically. Chemosphere, 2004 Dec, 57(11), 1733 - 8 Evaluation of antimicrobial agents for veterinary use in the ecotoxicity test using microalgae; Eguchi K et al.; The influence of antimicrobial agents approved as veterinary drugs in Japan on the growth of green algae, Selenastrum capricornutum and Chlorella vulgaris, was studied in accordance with the OECD guidelines for testing chemicals . Among the agents tested, growth inhibitory activity was very varied, i.e . erythromycin showed the strongest activity (EC50, 50% effective concentration, = 0.037 mg/l), sulfa drugs had activity to some extent (EC50s of sulfamethoxazole, sulfadiazine, and sulfadimethoxine were 1.5, 2.2, and 2.3 mg/l, respectively), but ampicillin and cefazolin did not inhibit growth (EC50s>1000 mg/l) . We also investigated synergistic effect of combining sulfa drugs with trimethoprim or pyrimethamine, which are commonly used as a combined drug . By adding trimethoprim, the growth inhibitory activity of sulfamethoxazole and sulfadiazine was significantly enhanced . Growth inhibition by sulfa drugs was reduced by the addition of folic acid, indicating that they inhibit folate synthesis in green algae. J Dermatol Sci, 2004 Nov, 36(2), 87 - 95 Effect of defensin peptides on eukaryotic cells: primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines; Nishimura M et al.; BACKGROUND: Although the usefulness of the antimicrobial peptides known as defensins has been suggested against oral and skin infections, possible adverse effects of the defensins on the host should be understood before clinical applications can be contemplated . OBJECTIVE: In the present study, we investigated how alpha-defensin (HNP-1) and beta-defensins (hBD-1, -2, -3) affect cells including primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines, SCC-9 and KB . METHOD: Cell proliferation was assessed by the direct cell counting and XTT assay . RESULTS: We found that alpha-defensin promotes proliferation of the epithelial cells at low concentration but has a cytotoxic effect at high concentration . In contrast, beta-defensins have little effect on these cells at any concentration, suggesting that beta-defensins may have no adverse effects on the host . CONCLUSION: Therefore, in terms of host response beta-defensins may be more suitable antimicrobial agents for clinical applications than alpha-defensins. BMC Public Health . 2004 Nov 1;4(1):50. A systematic review of the effectiveness of antimicrobial rinse-free hand sanitizers for prevention of illness-related absenteeism in elementary school children; Meadows E et al.; BACKGROUND: Absenteeism due to communicable illness is a major problem encountered by North American elementary school children . Although handwashing is a proven infection control measure, barriers exist in the school environment, which hinder compliance to this routine . Currently, alternative hand hygiene techniques are being considered, and one such technique is the use of antimicrobial rinse-free hand sanitizers . METHODS: A systematic review was conducted to examine the effectiveness of antimicrobial rinse-free hand sanitizer interventions in the elementary school setting . MEDLINE, EMBASE, Biological Abstract, CINAHL, HealthSTAR and Cochrane Controlled Trials Register were searched for both randomized and non-randomized controlled trials . Absenteeism due to communicable illness was the primary outcome variable . RESULTS: Six eligible studies, two of which were randomized, were identified (5 published studies, 1 published abstract) . The quality of reporting was low . Due to a large amount of heterogeneity and low quality of reporting, no pooled estimates were calculated . There was a significant difference reported in favor of the intervention in all 5 published studies . CONCLUSIONS: The available evidence for the effectiveness of antimicrobial rinse-free hand sanitizer in the school environment is of low quality . The results suggest that the strength of the benefit should be interpreted with caution . Given the potential to reduce student absenteeism, teacher absenteeism, school operating costs, healthcare costs and parental absenteeism, a well-designed and analyzed trial is needed to optimize this hand hygiene technique. J Pak Med Assoc, 2004 Sep, 54(9), 469 - 72 Multi-drug resistant tuberculosis in Northern Pakistan; Butt T et al.; OBJECTIVE: To determine the resistance pattern of Mycobacterium tuberculosis isolates in Rawalpindi-Islamabad . METHODS: The study was carried out at the Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi between September 2000 and August 2002 . We examined 1359 pulmonary and extra-pulmonary specimens from suspected cases of tuberculosis . The radiometric Bactec 460 TB system was used for culture and antimicrobial susceptibility testing . RESULTS: Mycobacterium tuberculosis was isolated from 325 clinical specimens . Antimicrobial susceptibility of the isolates was tested against the four first-line anti-tuberculous drugs (rifampicin, isoniazid, streptomycin and ethambutol) . Fifteen percent of the isolates were resistant to a single drug, 28% were multi-drug resistant including 7% which were resistant to all the four drugs . The overall resistance against individual drugs was rifampicin 32%, isoniazid 37%, streptomycin 19% and ethambutol 17% . CONCLUSIONS: The increasing level of drug resistance among mycobacterial isolates in our population is most alarming . Strict implementation of control measures is required to combat this unfolding crisis. Adv Neonatal Care, 2004 Oct, 4(5), 258 - 73 Linking the sepsis triad of inflammation, coagulation, and suppressed fibrinolysis to infants; Short MA; Sepsis continues to be a significant cause of morbidity and mortality in hospitalized newborns and premature infants . The pathophysiology and disease state of sepsis appear to be similar between adults and children . Both groups display symptoms that indicate a systemic inflammatory response leading to coagulopathy, hypotension, inadequate perfusion of peripheral tissues and organs, and, ultimately, organ failure and death . By presenting a comparison of adult and neonatal pathophysiology, as well as a supporting literature review and clinical evidence, this article links the pathways of inflammation, activation of coagulation, and impaired fibrinolysis, known as the sepsis cascade, to neonatal sepsis . Knowledge of the pathophysiology has important clinical and research implications . Unlike traditional antimicrobial therapy, new potential therapies, currently under investigation for the treatment of sepsis, target the cellular response rather than the invading organism . A more complete understanding of the pathophysiology of sepsis may also lead to diagnostic tools with improved sensitivity and specificity for early recognition and treatment. Oecologia, 2005 Jan, 142(2), 232 - 7 Epub 2004 Oct 29. The persistence of ripe fleshy fruits in the presence and absence of frugivores; Tang AM et al.; A trade-off between antimicrobial defences and palatability to dispersers may place limits on fruit persistence in nature . The retention times of ripe fruits on 34 wild plant species under natural conditions (unbagged persistence) and when fruits had been bagged with nylon mesh to exclude frugivores (bagged persistence) were compared in Hong Kong, China (22 degrees N) . Bagged persistence is a measure of the effectiveness of fruit defence while unbagged persistence is an inverse measure of attractiveness to vertebrate frugivores . Bagged fruits persisted significantly longer than unbagged fruits in 30 species, with half the species tested persisting for more than 2 months . There was a significant positive relationship between the median persistence times of bagged and unbagged fruits, suggesting that species with a high resistance to microbial infection are also less attractive to frugivores . Both bagged and unbagged fruits persisted significantly longer at lower temperatures . There was a significant positive relationship between ba