Int J Dermatol, 2000 Oct, 39(10), 784 - 8 Adapalene: an update on newer comparative studies between the various retinoids; Millikan LE; BACKGROUND: Extensive modification of the retinoic acid molecular skeleton has resulted in the development of adapalene, a more stable, less irritating compound with receptor selectivity . Adapalene selectively targets nuclear retinoic acid receptors found primarily in the epidermis . Pharmacologic and preclinical studies have demonstrated excellent follicular penetration, comedolytic activity, and anti-inflammatory activity . METHODS: Recent comparative trials were reviewed . RESULTS: Adapalene is a useful new agent because of its tolerability and stability . It is a good therapeutic choice for combination with other topical anti-acne medications, such as antimicrobials or benzoyl peroxide . Patient compliance with either combination or single-agent adapalene regimens is likely to be enhanced because of the greater comfort and reduced skin irritation associated with the new compound . Other investigators have confirmed that adapalene gel produces consistent and significantly reduced irritation . CONCLUSIONS: Recent comparative trials on retinoids have provided new data to aid in the selection of the appropriate combination of topical agents for individual patients. Anaesth Intensive Care, 2000 Oct, 28(5), 475 - 90 Can we achieve consensus on central venous catheter-related infections? Fraenkel DJ, Rickard C, Lipman J. Central venous catheter-related bacteraemia is a substantial and preventable source of iatrogenic morbidity and mortality . A single episode of catheter-related bacteraemia has an estimated cost of A$50,000, with an attributable mortality between 10 and 35% . Catheter colonization is diagnosed with standard culture techniques . Diagnostic criteria for catheter-related bacteraemia include the results of cultures from the catheter tip, the peripheral blood and other possible sites of infection . The presence of clinical symptoms and subsequent defervescence may assist in making the diagnosis . This review explores the existing definitions of catheter-related infections and proposes a new and more rigorous classification with criteria for definite, probable and possible catheter-related bacteraemia . The authors hope that this classification will enhance the interpretation of the literature and the planning of new investigations . Infection rates can be reduced by appropriate site selection, adequate skin preparation, sterile technique and appropriate dressings . Decreased manipulation of administration sets, with more careful technique and less frequent set replacement, may reduce hub contamination . Infection rates increase with the duration in situ of the catheter, however are not reduced by regular scheduled catheter replacement or guide-wire exchanges . A range of antimicrobial catheter materials and coatings are under investigation, some of which are effective in reducing the rate of catheter-related bacteraemia . Chorhexidine-silver sulphadiazine and rifampicin-minocycline are the best studied combinations to date . Further developments are expected, although none are likely to be as effective as not inserting or removing the central venous catheter when it is not required. Curr Treat Options Gastroenterol, 1999 Jun, 2(3), 251 - 257 Diarrhea in the International Traveler; Duchini A et al.; International travelers to developing countries have a 40% risk of developing a diarrheal illness, usually acute and occasionally chronic . Preventive measures, including diet and lifestyle modifications, are highly recommended but may not be sufficient . Prophylaxis with bismuth subsalicylate or an antimicrobial should be considered in travelers with immunodeficiencies, co-morbid conditions, achlorhydria, or those who cannot afford a loss of time . Oral rehydration is the primary goal of therapy . Bismuth-subsalicylate is a first-line agent for treatment of milder cases with less than three watery bowel movements per day and prominent nausea . Use of an antibiotic is indicated for more severe cases or in the presence of fever, dysentery, or severe dehydration . A short course of a quinolone is highly effective, safe and well tolerated . Antimicrobial resistance among enteropathogens is growing and appropriate therapeutic modifications should be considered according to specific geographic areas . Metronidazole may be empirically added in those cases that do not respond to quinolones . Specific guidelines for particular pathogens are highlighted. Curr Treat Options Neurol, 1999 May, 1(2), 157 - 166 Brain Abscess; Davis LE et al.; Optimal treatment of a brain abscess requires early clinical suspicion, and the diagnosis is usually made by identification of the abscess on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) . The immediate first step is to reduce the potentially life-threatening brain mass (abscess and surrounding cerebral edema) and secure the diagnosis with culture specimens . This is usually accomplished by reducing the increased intracranial pressure (ICP) through surgical aspiration with or without drainage of the abscess pus . The surgical procedure chosen depends on several factors, including the location and type of abscess, multiplicity, and the medical condition of the patient . In addition, dexamethasone and hyperventilation may be required if brain herniation is imminent . The dexamethasone dose should be reduced as soon as the ICP is reduced because steroid administration may retard abscess capsule formation and decrease antibiotic concentrations within the abscess cavity . Antibiotic therapy should be started as soon as the diagnosis is made . Penicillin G or third-generation cephalosporins plus metronidazole are commonly given to treat both anaerobic and aerobic bacteria . The initial choice of antibiotic will vary on the basis of the suspected source of the brain organisms, which is most often either contiguous spread from a sinus or mastoid infection or hematogenous spread from a pulmonary, gastrointestinal, cardiac, or dental infection . Isolation and determination of the antibiotic sensitivities of the organism from abscess pus allow definitive antibiotic therapy . Patients should be managed in an intensive care unit . Phenytoin is often given to prevent seizures, which could further elevate the ICP . The duration of antimicrobial treatment is 4 to 8 weeks, during which time the patient should be monitored clinically and with repeated neuroimaging studies to ensure abscess resolution. Curr Interv Cardiol Rep, 2000 Nov, 2(4), 342 - 348 Infectious Agents, Antibiotics, and Coronary Artery Disease; Muhlestein JB; Atherosclerotic cardiovascular disease, the major cause of death in the Western world, is a multi-factorial process with a large number of interacting variables . Despite a significant understanding of many of these variables, the underlying causes of atherosclerosis are still not clearly defined . Recent studies have documented a possible association between chronic inflammation and a variety of chronic bacterial infections (including Chlamydia pneumoniae, Helicobacter pylori, and a variety of periodontal infectious agents) and the development or progression of atherosclerosis . Because these bacterial agents are sensitive to a variety of antibiotic agents, it has been proposed that antimicrobial therapy might be useful in the primary or secondary prevention of atherosclerosis . This article reviews the evidence supporting an association between chronic bacterial infection and atherosclerosis, describes the results of preliminary secondary prevention antibiotic treatment trials, and discusses a variety of ongoing and planned large multicenter clinical trials of antibiotics in patients with atherosclerotic heart disease . Potential pitfalls associated with the broad use of antibiotics to treat heart disease are also discussed. Curr Treat Options Gastroenterol, 1998 Dec, 1(1), 1 - 7 Diabetic and Nondiabetic Gastroparesis; McCallum RW et al.; Nutritional support is essential in treating patients with gastroparesis . Initially, dietary changes should be instituted to reduce extra fat and bulk, and patients should be encouraged to eat frequent small meals with liquid supplementation . Enteral feeding should be introduced in the event of weight loss or persistent vomiting . Medical therapy is usually necessary early in treatment . Cisapride is the initial agent of choice and may be combined with an antiemetic agent, such as promethazine or chlorpromazine or, if side effects occur, ondansetron and granesitron . If cisapride is ineffective or contraindicated, metoclopramide is a reasonable option, though limited by side effects . Erythromycin is useful in the acute treatment of postoperative ileus and hospitalized gastroparetic patients, but its role is limited based on concerns about poor long-term effectiveness and antimicrobial resistance . Once domperidone becomes available in the United States, it will be useful for its promotility and antiemetic qualities . Combination therapy should be considered if monotherapy with cisapride or metoclopramide alone is ineffective . While not yet well studied, combination therapy has the potential to offer dramatic benefit for patients with refractory gastroparesis . Metoclopramide may be added to cisapride for patients with breakthrough symptoms or refractory chronic symptoms . Other combinations include metoclopramide with erythromycin, domperidone with cisapride, and domperidone with erythromycin . In the future, gastric pacing may become an effective option for patients not responding to medical therapy . Total gastrectomy should be performed only for end-stage gastroparesis when all other therapy has failed . Both procedures should be reserved for centers that specialize in severe gastric motility disorders. Curr Infect Dis Rep, 2000 Oct, 2(5), 409 - 416 Impact of Antibiotic Resistance on the Treatment of Gram-negative Sepsis; Baden LR et al.; Resistance among gram-negative organisms has greatly complicated the care of the septic patient . An understanding of the likely source of infection, the epidemiologic risk of the patient being exposed to an antibiotic-resistant organism, and the specific vulnerabilities of the host are essential to the proper selection of empiric antimicrobial therapy . In this report, we discuss the epidemiology, antibiotic resistance mechanisms, microbiology, treatment strategies, and diagnostic and therapeutic innovations in the approach to the septic patient. Curr Infect Dis Rep, 2000 Aug, 2(4), 365 - 370 HIV Treatment in Developing Countries; Mason PR et al.; Diagnostic, prognostic and therapeutic advances have had a major impact on HIV at both the individual and community levels in wealthy nations . However, more than 95% of HIV infections occur in developing countries, where personal or national economies cannot support these measures . Therefore, HIV treatment in developing countries must focus on particular aspects of infection, especially prevention and treatment of those opportunistic infections for which inexpensive antimicrobial agents are available and effective . At present, the focus in developing countries is on tuberculosis, Pneumocystis carinii pneumonia (PCP), and pneumococcal pneumonia . The spread of antimicrobial resistance in mycobacteria and pneumococci is of special concern for developing countries, and strategies to limit the spread of resistance should take high priority . The use of specific antiretroviral agents is limited, because of cost, to prevention of mother-to-child transmission, and notable successes have been achieved . While it is unlikely that these agents will become widely available to the general population, targeting treatment at high-risk groups, through a program of post-exposure prophylaxis, may be an affordable strategy in some situations. Curr Infect Dis Rep, 1999 Dec, 1(5), 488 - 494 "Essentiality" Testing: Looking for New Antimicrobial Targets; Knowles D et al.; After a gap of some 30 years, the prospect of finding completely new agents with which to combat infectious disease is promising . New discovery approaches based on the application of genomics and associated technologies are leading to the identification of genes essential for bacterial viability and pathogenesis . This article reviews the current status of the search for new antimicrobial targets and points to future developments and issues. Curr Infect Dis Rep, 1999 Dec, 1(5), 480 - 487 Quinupristin-Dalfopristin; Linden P; The incidence of infection with multidrug-resistant or pan-resistant gram-positive bacteria has drastically limited or eliminated the conventional antimicrobial options available to clinicians . Quinupristin-dalfopristin, a unique parenteral streptogramin that lacks cross-resistance with other antimicrobials, has shown clinical efficacy against many of these important bacteria . This review focuses on quinupristin-dalfopristin"s mechanism of action, in vitro spectrum of activity, clinical efficacy and toxicity, and likely future role in the management of serious gram-positive infections. Curr Infect Dis Rep, 1999 Dec, 1(5), 464 - 469 Superbugs: How They Evolve and Minimize the Cost of Resistance; Low DE et al.; The increasing frequency with which antimicrobial-resistant microorganisms have emerged in hospitals and communities has alarmed public health officials worldwide . The emergence of resistance results from the evolution of the sometimes elegant resistance mechanisms that create so-called superbugs, which disseminate by clonal spread or exchange resistance traits with other microorganisms . One major contributor to the emergence of resistance is selection intensity, which is determined by the volume of drug consumption by humans and the agriculture industry . De novo or acquired resistance is often initially associated with a cost to fitness of the microorganism . It therefore seems reasonable to assume that reducing the volume of drug use would slow the evolution and reduce the prevalence of resistance . This assumption has led to worldwide attempts to control the inappropriate use of antimicrobials in the hope of controlling the pandemic of antibiotic resistance . However, microorganisms have learned to adapt in order to survive in ever-changing environments . Superbugs have evolved numerous mechanisms that reduce or eliminate the cost of resistance, and such adaptations may minimize the potential benefits of programs aimed at reducing the volume of drug use . It therefore behooves us to look to other disciplines--such as population genetics, ecology, and mathematical biology--to help us tackle this perplexing and important problem. Curr Infect Dis Rep, 1999 Oct, 1(4), 334 - 337 Role of Antimicrobial Stewardship in Prevention and Control of Antibiotic Resistance; Shlaes DM; Evidence linking antimicrobial use with resistance is compelling on the local, national, and international levels . That resistance levels can be influenced by changing patterns of use also seems clear . We must now determine how, as a global society, to best use the resource of antimicrobials and how to protect novel compounds that are just now becoming available from emerging resistance . We must act not only within the arena of human use but also on use in animals and for crops. Curr Infect Dis Rep, 1999 Aug, 1(3), 218 - 223 Colony-Stimulating Factors in the Therapeutic Approach to Sepsis; Alcid DV et al.; Sepsis and its complications continue to be a leading cause of death in the United States despite availability of potent broad-spectrum antimicrobial agents . Current in vitro, ex vivo, animal, and human data are reviewed . Present data shows that colony-stimulating factors (CSFs), granulocyte CSFs, and granulocyte-macrophage CSFs are very effective in raising the leukocyte count and shortening the number of neutropenic days . CSFs in some studies improved outcome of neutropenic septic patients especially when given very early . However, there are studies that do not show any benefit . CSFs appear to be safe and should be limited to septic, neutropenic patients whose duration of neutropenia is anticipated to be prolonged, or to patients who are seriously ill. Curr Infect Dis Rep, 1999 Jun, 1(2), 166 - 171 Brain Abscess, Subdural Empyema, and Intracranial Epidural Abscess; Calfee DP et al.; Brain abscess, subdural empyema, and intracranial epidural abscess are three of the most commonly encountered focal suppurative processes of the central nervous system . A great deal has been known about the epidemiology and pathogenesis of these entities for quite some time, but until recent years the associated morbidity and mortality remained very high . New imaging techniques have allowed for more rapid detection and more precise localization of these lesions for surgical drainage . Empiric antimicrobial regimens that are effective within the abscess environment and that are directed against the most likely pathogens have also contributed to the improved outcomes seen in the current literature . This article will discuss some of the more recent advances in the diagnosis and treatment of these suppurative lesions within the central nervous system. Curr Infect Dis Rep, 1999 Jun, 1(2), 119 - 125 Infective Endocarditis: Current Guidelines on Prophylaxis; Levison ME et al.; Prevention of infective endocarditis is a priority because this disease is associated with considerable morbidity and mortality both during the acute phase of the illness and subsequently, despite modern medical and surgical treatment . The American Heart Association has published recommendations for prevention by antimicrobial prophylaxis since 1955; the most recent revision of these guidelines appeared in 1997 . All practicing physicians should know their content and understand their underlying concepts and assumptions. Curr Infect Dis Rep, 1999 Apr, 1(1), 99 - 104 Immune Reconstitution and the Consequences for Opportunistic Infection Treatment and Prevention; Powderly WG; Effective antiretroviral therapy that suppresses HIV replication is associated with dramatic increases in CD4 counts . Recent evidence suggests that this CD4 cell increase is biphasic in nature, with an initial phase (in the first 2 to 3 months) that represents redistribution of lymphocytes into the periphery and a second phase that is associated with true immunologic recovery and reconstitution . Immunologically there is evidence of increase in naive T cells, recovery of in vitro responses to microbial antigens, and repair of the damaged diversity of T cells . Clinically, this immune recovery has been characterized by decreasing morbidity and mortality from opportunistic infections, an ability to treat previously intractable infections, immune-mediated syndromes, and increasing reports of the ability to discontinue primary and secondary prophylaxis . Although there are still unresolved questions about the completeness of the immune recovery, most available evidence suggests in most patients the degree of immune reconstitution with effective antiretroviral therapy is sufficient to be protective against most opportunistic infections, and ultimately additional antimicrobial prophylaxis will be unnecessary. Shock, 2000 Nov, 14(5), 555 - 60 Proinflammatory kupffer cell alterations after femur fracture trauma and sepsis in rats; Huynh T et al.; This study examined effects of trauma and sepsis on Kupffer cell function . When CBA/J mice had femur fracture (FFx), no deaths occurred . After cecal ligation and puncture (CLP), 44% died . Following combined injuries (FFx + CLP), mortality increased to 60%, suggesting a deleterious effect between FFx + CLP . Kupffer cell ablation with GdCI3 decreased mortality to 13% after CLP and 5% after FFx + CLP . After FFx, CLP, and FFx + CLP, Kupffer cells isolated from Sprague-Dawley rats produced 720%, 1,100%, and 2,130% more O2 . than sham, respectively . Phagocytosis increased 320%, 610%, and 150% . Kupffer cell PGE2 production also increased 300%, 510%, and 300% over sham . After FFx alone, TNF-alpha production decreased 40% . By contrast, CLP and FFx + CLP increased TNF-alpha release 25% and 100%, respectively . After FFx, NO . production decreased 44%, whereas NO increased 280% and 260% after CLP and FFx + CLP . These findings indicate that Kupffer cells mediate mortality after CLP and FFx + CLP . Increased mortality is associated with a more proinflammatory and less antimicrobial Kupffer cell phenotype. Bioorg Med Chem, 2000 Nov, 8(11), 2539 - 48 The interaction of analogues of the antimicrobial lipopeptide, iturin A2, with alkali metal ions; Rautenbach M et al.; Electrospray mass spectrometry was employed as a tool in this first study on the molecular interaction between the alkali metal ions and antifungal lipopeptide iturin A, and some analogues . Cationisation by sodium and signal intensity of lipopeptide species depended on sodium concentration, but was independent of sample solvent, carrier solvent polarity and sample pH between 4 and 11 . 8-Beta, a linear analogue of iturin A2 (8-Beta; beta-aminotetradecanoyl-NYNQPNS), and its shorter linear lipopeptide analogues, associated either one or two alkali metal cations, while the N-->C cyclic peptides associated with only one cation . The chirality of the beta-NC14 residue had a limited influence on the cationisation . It was observed that 8-Beta contained at least four interaction sites for a cation of which two, the C-terminal carboxylate and the side-chain of tyrosine, can take part in ionic interaction with a cation . It is proposed that the remaining two interaction centres of alkali metal ions are within the two type II beta-turns found in conformation of natural iturin A . This was corroborated by the diminished capacity of the shorter peptides, in which one of the beta-turns was eliminated to bind a second larger cation . All the lipopeptides showed the same order of alkali metal ion selectivity: Na+ > K+ > Rb+ . These results indicated a size limitation in the interaction cavity or cavities . The absence of, or observation of only low abundance, di-cationised complexes of cyclic peptides the indicated association of the cation in the interior of the peptide ring . It is thus hypothesised that alkali metal ions can bind in one of the two beta-turns in the natural iturin A molecule. Microbiol Immunol, 2000, 44(9), 749 - 54 Effect of ions on antibacterial activity of human beta defensin 2; Tomita T et al.; Human beta defensin 2 (HBD-2), the most recently discovered human defensin, has been considered to work as a host defense substance against microbial infection . Using Escherichia coli ATCC 25922, we investigated how some cations and anions influenced the antimicrobial activity of HBD-2 . This activity, measured in 10 mM phosphate buffer at a concentration of 20 microg/ml, reduced significantly in the presence of 100 and 150 mM sodium or potassium chloride . The reduction was not significantly different when the total amounts of sodium and potassium ions were equal . The kind and the valence of anions (chlorine and sulfate ions) did not affect the bactericidal activity as long as the concentrations of sodium ions were equal . Divalent ions (calcium and magnesium ions) added to 10 mM of Tris buffer significantly inactivated HBD-2 at much lower concentrations (more than or equal to 0.01 mM and 0.05 mM, respectively) than the monovalent ions did . These findings suggest that HBD-2 kills the bacteria through at least two phases, which are affected independently by either monovalent or divalent ions and unaffected by anions. Int J Antimicrob Agents, 2000 Nov, 16(3), 303 - 7 The role of antimicrobial policies in neutropenic patients; Martino P et al.; Antimicrobial policies in neutropenic patients are under continual review . The development of more potent broad spectrum antibiotics has allowed new approaches to empiric antibiotic therapy, including the use of a single agent rather than an antibiotic combination . The standard clinical approach in cancer patients with persistent, severe neutropenia, is hospitalization until the infective complication has resolved, but an accurate clinical stratification of patients based on different medical risks could suggest different approaches to infective complications . The desire of cancer patients to spend as much time as possible at home during the palliative or terminal phase of their illness and the high costs of hospitalization are the main motives behind the early discharge of patients from hospital and the development of strategies that move traditionally inpatient problems or therapies, to the outpatient setting. Int J Antimicrob Agents, 2000 Nov, 16(3), 295 - 9 Impact of an antimicrobial formulary and restriction policy in the largest hospital in Italy; Bassetti M et al.; We have analysed the expenditure on antimicrobial drugs in the largest hospital in Italy; over this period, a committee prepared an antibiotic policy document . This formulary lists all antimicrobial drugs available in the hospital . Some drugs were removed from the list and others are only available on special request for a named patient . In the hope of optimising drug utilisation, we included all the reasons for the choice of agent in the document . The introduction of this formulary resulted in an immediate saving and perhaps in the future we shall also observe an improvement in bacterial resistance patterns. Int J Antimicrob Agents, 2000 Nov, 16(3), 191 - 7 Development and persistence of multi-resistance to antibiotics in bacteria; an analysis and a new approach to this urgent problem; van der Waaij D et al.; The intestinal microflora may have more influence on infectious diseases, than the mere control of growth of opportunistic micro-organisms by colonisation resistance (CR) and unspecific stimulation of the immune system . In compromised patients the CR may become decreased for several reasons but mostly because antibiotics reach the intestine during treatment . The consequence of a CR-decrease is that antibiotic-resistant opportunistic micro-organisms may increase in numbers in the gut . In this context, it is hypothesised that if the CR could be maintained at a normal level, the risk for maintenance and spread of resistant strains could be mitigated . Such maintenance requires absence of active antibiotic substance in the gut . This might be brought by the inactivation of antimicrobial agents by intestinal contents . Intra-intestinal inactivation has been described to occur along two possible routes: (1) inactivation by chemical binding or absorption and (2) by enzymatic destruction . Secondly, the composition of the intestinal microflora should be maintained at a normal level in case of other reasons for CR-decrease than antibiotic activity . Comprehensive study of the composition of normal microflora and the strains of species which play a role in CR with techniques which have become available during last decade, is recommended as well as the application of certain pre- and probiotics . It is concluded that antibiotic inactivation may be an ancient strategy of nature which should become incorporated in antibiotic treatment . Antibiotic use and development of resistance may have occurred when ecosystems formed several billions of years ago . Protection against antibiotics produced by newcomers into the ecosystem may have developed as it was necessary to maintain locally available nutrients for the inhabitants of the ecosystem . Should this hypothesis be correct, it is plausible that antimicrobial inactivation by antibiotic inactivating molecules is ubiquitous . In the ecosystem of the digestive tract, molecules involved in inactivation may predominantly be formed by microorganisms. Peptides, 2000 Nov, 21(11), 1681 - 6 Sequence of a gene from Bombina orientalis coding for the antimicrobial peptide BLP-7; Miele R et al.; The structure of a gene coding for bombinin-like peptides (BLP) in Bombina orientalis was determined . It comprises two exons separated by a 1337 bp intron . Exon 1 codes for the signal peptide, while exon 2 contains the genetic information for BLP-7 and a bombinin H-type peptide (GH-2) . The promoter region contains putative recognition sites for nuclear factors, such as NF-IL6 and NF-kappaB . The analysis of the structure of this gene, compared with that of the previously reported BLP-3 gene sequence, suggests the occurrence of a gene duplication event, rather than an alternative splicing mechanism, which leads to the generation of both inter- and intra-families variability in this class of cytolytic peptides . Furthermore, chromosome walking analysis indicates that this gene family is not densely clustered. Peptides, 2000 Nov, 21(11), 1673 - 9 Structure-function relationships in bombinins H, antimicrobial peptides from Bombina skin secretions; Mangoni ML et al.; Skin secretions of amphibia of the Bombina genus contain two families of antimicrobial peptides, the bombinins (bombinin-like peptides) and the bombinins H (H for hydrophobic and hemolytic) . The latter family includes a number of peptides containing a D-amino acid in the second position, in addition to their corresponding all L-isomers . The antimicrobial activity of three pairs of bombinin H isomers, H2/H4, H6/H7 and GH-1D/GH-1L, has been investigated . The first two pairs of peptides were actually isolated from the secretion, whereas the third was synthesized according to the sequence deduced from a gene coding for a bombinin-like peptide in Bombina orientalis. Aquat Toxicol, 2001 Jan, 51(3), 351 - 62 Combined effects of pentachlorophenol and salinity stress on chemiluminescence activity in two species of abalone; Martello LB et al.; The effect of pentachlorophenol (PCP) combined with salinity stress on hemocyte microbicidal activity was examined in two species of abalone . Microbicidal phagocytic function was determined in red (Haliotis rufescens) and black (Haliotis cracherodii) abalone after in vivo exposure to 25, 35 and 45 per thousand seawater salinity plus 1.2 mg/l PCP using luminol-dependent chemiluminescence (CL) . Red and black abalone exposures of 3.5 and 6.5 h, respectively, were based on species-specific metabolic endpoints (MEPs) derived from previous nuclear magnetic resonance spectroscopy (NMR) data . Endpoints examined include total CL (CL(total)), peak CL (CL(max)), and the time to reach peak CL (T(max)) . Overall, black abalone CL was significantly greater than red abalone CL particularly at ambient and high salinities . High salinity alone had a dramatic effect on red abalone whereas black abalone demonstrated few salinity effects . While the addition of PCP stimulated CL(max) and CL(total) among red abalone at ambient and high salinities, PCP exposure inhibited CL(max) at each salinity and inhibited CL(total) at ambient salinity among black abalone . Black abalone generally did not demonstrate effects of PCP within the 3.5 h exposure period except at high salinity plus PCP, which caused a reduction of CL(total) . T(max) was greatly increased after PCP exposure at each salinity among red abalone but did not effect T(max) at any salinity tested among black abalone . No lysozyme activity was detected among red or black abalone after exposure to any of four different target particles tested either in the presence or absence of PCP . Overall, PCP in combination with salinity stress causes a modulation in the production of reactive oxygen species and this modulation varies between abalone species . Agents that decrease CL activity in hemocytes may reduce the antimicrobial potential of these cells thereby increasing susceptibility to infectious disease. Arch Intern Med, 2000 Nov 27, 160(21), 3234 - 40 Impact of zanamivir on antibiotic use for respiratory events following acute influenza in adolescents and adults; Kaiser L et al.; BACKGROUND: Influenza infections commonly lead to respiratory tract complications that result in antibiotic treatment . OBJECTIVES: To determine frequency of respiratory events leading to antibiotic use following influenza illness in adolescents and adults, and to assess whether treatment with topical zanamivir prevents these complications . METHODS: Meta-analysis of 7 randomized, double-blind, placebo-controlled trials; 3815 mainly healthy adolescents and adults (mean age, 34 years) with an influenzalike illness of less than 2 days' duration were randomly assigned to receive combined inhaled and intranasal zanamivir, inhaled zanamivir, or corresponding placebos . Twelve percent of enrolled subjects were high-risk patients . The main outcome was the incidence of respiratory events leading to antibiotic prescriptions in patients with proven influenza . RESULTS: Influenza infections were laboratory confirmed in 2499 (66%) of 3815 patients (influenza A in 88% and B in 12%) . Placebo recipients developed a respiratory event leading to antibiotic use in 17% of cases, mainly for acute bronchitis or acute sinusitis . Among zanamivir-treated patients (n = 1494) the incidence of respiratory events leading to the use of antimicrobials was 11% (relative risk {RR} compared with placebo, 0.69; 95% confidence interval {CI}, 0.57-0.84) . Intranasal and inhaled zanamivir seemed to reduce the number of upper (RR, 0.59; 95% CI, 0.36-0.97) and lower respiratory tract events (RR, 0.64; 95% CI, 0.38-1.08) . Inhaled zanamivir reduced the number of lower respiratory tract events (RR, 0.60; 95% CI, 0.42-0.85), but the reduction in the number of upper respiratory tract events was not statistically significant (RR, 0.90; 95% CI, 0.63-1.27) . CONCLUSIONS: Respiratory complications or worsening of symptoms leading to antibiotic use occurred in about 17% of adolescents or adults with influenza infection . Early treatment of influenza illness with zanamivir reduced the number of these antibiotic prescriptions . Arch Intern Med . 2000;160:3234-3240. Biochim Biophys Acta, 2000 Nov 30, 1543(1), 95 - 105 Multiple antimicrobial peptides and peptides related to bradykinin and neuromedin N isolated from skin secretions of the pickerel frog, Rana palustris; Basir YJ et al.; The skin secretions of the North American pickerel frog Rana palustris are toxic to both microorganisms and predators . A total of 22 peptides with differential growth-inhibitory activity towards bacteria and yeast were isolated from the electrostimulated secretions of R . palustris skin and were characterized structurally . Thirteen of the antimicrobial peptides belong to five of the known families previously identified in the skins of other species of Ranid frogs: brevinin-1 (3 peptides), esculentin-1 (2 peptides), esculentin-2 (1 peptide), ranatuerin-2 (6 peptides), and temporin (1 peptide) . Nine peptides show little structural similarity towards other known antimicrobial peptides and so are classified in new families: palustrin-1 (4 peptides) with 27-28 amino acid residues and a cystine-bridged heptapeptide ring; palustrin-2 (3 peptides) with 31 amino acids and a cyclic heptapeptide region and palustrin-3 (2 peptides) with 48 amino acids and a cyclic hexapeptide region . Peptides belonging to the esculentin-1, esculentin-2 and palustrin-3 families are the most potent (minimal inhibitory concentrations approximately 1 microM against Escherichia coli) whereas peptides of the brevinin-1 and esculentin-2 families show the broadest spectrum of activity . As well as bradykinin that is identical to the human peptide, a further 4 peptides structurally related to {Leu(8)}bradykinin and two peptides related to neuromedin-N (the hexapeptide KKPYIL and a larger, cystine-containing form HLRRCGKKPYILMACS) were purified from the skin secretions. J Nat Prod, 2000 Nov, 63(11), 1524 - 6 Nostocyclyne A, a novel antimicrobial cyclophane from the cyanobacterium Nostoc sp; Ploutno A et al.; A novel acetylene-containing para-{14}-cyclophane, nostocyclyne A (1), possessing antimicrobial activity, is the major active metabolite of the natural bloom of the cyanobacterium Nostoc sp . (TAU strain IL-220) . Homonuclear and heteronuclear 2D NMR techniques as well as HREIMS determined the gross structure of 1. J Agric Food Chem, 2000 Nov, 48(11), 5702 - 9 Cinnamaldehyde content in foods determined by gas chromatography-mass spectrometry; Friedman M et al.; trans-Cinnamaldehyde, the principal component of cinnamon flavor, is a potent antimicrobial compound present in essential oils such as cinnamon . In the course of studies designed to discover its maximum microbial lethality under food-processing conditions, a gas chromatographic-mass spectrophotometric procedure was developed for the extraction and analysis of essential oil components such as cinnamaldehyde from commercial cinnamon-containing foods (several brands of cinnamon breads, cereals, cookies, puddings, applesauces, and fruit juices) . The cinnamaldehyde content ranged from trace amounts in orange juice to 12.2 mg/100 g (122 ppm) in apple cinnamon cereals and 31.1 mg/100 g (311 ppm) for cinnamon swirl bread (highest value) . To ascertain the heat stability of cinnamaldehyde, pure cinnamaldehyde, pure eugenol, cinnamon oil, and mixtures consisting of cinnamaldehyde plus eugenol or cinnamon oil were heated at graded temperatures up to 210 degrees C and 60 min, and then possible compositional changes were examined . Eugenol was stable to heat, as were the components of cinnamon oil: carvone, eugenol, and linalool . In contrast, starting at approximately 60 degrees C, pure cinnamaldehyde undergoes a temperature-dependent transformation to benzaldehyde under the influence of heat . Eugenol, both pure and in cinnamon oil, when added to pure cinnamaldehyde protected the aldehyde against heat destruction . The protection may due to an antioxidative action of eugenol . The possible mechanism of this effect and the significance of these findings for food chemistry and microbiology are discussed. Biochemistry, 2000 Nov 28, 39(47), 14436 - 47 Solution structure and activity of the synthetic four-disulfide bond Mediterranean mussel defensin (MGD-1); Yang YS et al.; MGD-1 is a 39-residue defensin-like peptide isolated from the edible Mediterranean mussel, Mytilus galloprovincialis . This peptide is characterized by the presence of four disulfide bonds . We report here its solid-phase synthesis and an easy way to improve the yield of the four native disulfide bonds . Synthetic and native MGD-1 display similar antibacterial activity, suggesting that the hydroxylation of Trp28 observed in native MGD-1 is not involved in the antimicrobial effect . The three-dimensional solution structure of MGD-1 has been established using (1)H NMR and mainly consists of a helical part (Asn7-Ser16) and two antiparallel beta-strands (Arg20-Cys25 and Cys33-Arg37), together giving rise to the common cystine-stabilized alpha-beta motif frequently observed in scorpion toxins . In MGD-1, the cystine-stabilized alpha-beta motif is stabilized by four disulfide bonds (Cys4-Cys25, Cys10-Cys33, Cys14-Cys35, and Cys21-Cys38), instead of by the three disulfide bonds commonly found in arthropod defensins . Except for the Cys21-Cys38 disulfide bond which is solvent-exposed, the three others belong to the particularly hydrophobic core of the highly constrained structure . Moreover, the C4-P5 amide bond in the cis conformation characterizes the MGD-1 structure . MGD-1 and insect defensin A possess similar bactericidal anti-Gram-positive activity, suggesting that the fourth disulfide bond of MGD-1 is not essential for the biological activity . In agreement with the general features of antibacterial peptides, the MGD-1 and defensin A structures display a typical distribution of positively charged and hydrophobic side chains . The positively charged residues of MGD-1 are located in three clusters . For these two defensin peptides isolated from insects and mollusks, it appears that the rather well conserved location of certain positively charged residues and of the large hydrophobic cluster are enough to generate the bactericidal potency and the Gram-positive specificity. Biochemistry, 2000 Nov 21, 39(46), 14150 - 9 Interaction between heat shock proteins and antimicrobial peptides; Otvos L Jr et al.; Drosocin, pyrrhocoricin, and apidaecin, representing the short (18-20 amino acid residues) proline-rich antibacterial peptide family, originally isolated from insects, were shown to act on a target bacterial protein in a stereospecific manner . Native pyrrhocoricin and one of its analogues designed for this purpose protect mice from bacterial challenge and, therefore, may represent alternatives to existing antimicrobial drugs . Furthermore, this mode of action can be a basis for the design of a completely novel set of antibacterial compounds, peptidic or peptidomimetic, if the interacting bacterial biopolymers are known . Recently, apidaecin was shown to enter Escherichia coli and subsequently kill bacteria through sequential interactions with diverse target macromolecules . In this paper report, we used biotin- and fluorescein-labeled pyrrhocoricin, drosocin, and apidaecin analogues to identify biopolymers that bind to these peptides and are potentially involved in the above-mentioned multistep killing process . Through use of a biotin-labeled pyrrhocoricin analogue, we isolated two interacting proteins from E . coli . According to mass spectrometry, Western blot, and fluorescence polarization, the short, proline-rich peptides bound to DnaK, the 70-kDa bacterial heat shock protein, both in solution and on the solid-phase . GroEL, the 60-kDa chaperonin, also bound in solution . Control experiments with an unrelated labeled peptide showed that while binding to DnaK was specific for the antibacterial peptides, binding to GroEL was not specific for these insect sequences . The killing of bacteria and DnaK binding are related events, as an inactive pyrrhocoricin analogue made of all-D-amino acids failed to bind . The pharmaceutical potential of the insect antibacterial peptides is underscored by the fact that pyrrhocoricin did not bind to Hsp70, the human equivalent of DnaK . Competition assay with unlabeled pyrrhocoricin indicated differences in GroEL and DnaK binding and a probable two-site interaction with DnaK . In addition, all three antibacterial peptides strongly interacted with two bacterial lipopolysaccharide (LPS) preparations in solution, indicating that the initial step of the bacterial killing cascade proceeds through LPS-mediated cell entry. Mycopathologia, 1999, 148(1), 25 - 31 Antimicrobial susceptibility testing of dematiaceous filamentous fungi: effect of medium composition at different temperatures and times of reading; Llop C et al.; We examined the effects of the composition of five media on the MICs of three antifungal agents (amphotericin B, flucytosine and ketoconazole) against 24 dematiaceous fungi at different temperatures and times of reading . Media studied were RPMI 1640, tryptic soy broth (TSB), yeast nitrogen broth (YNB), casein-yeast-glucose broth (CYG) and high-resolution medium (HR) . The degree of reproducibility was determined with ketoconazole and 5-fluorocytosine and the media TSB and RPMI showed the best results with ketoconazole, while the best results for flucytosine were in CYG . Reproducibility was higher at 25 degrees than at 30 degrees C . The media and incubation time were shown to have a significant influence on the MICs of the three antifungals, but there were no interactions between these variables and temperature, except in the case of ketoconazole, where media-temperature and media-incubation time interactions were significant . There were noteworthy differences between the MICs obtained with the different media. Braz J Infect Dis, 1999 Oct, 3(5), 180 - 183 Pharmacy Distribution of Advice, Symptomatic Treatment and Antimicrobial Drugs to Patients with Cough; Cadore LP et al.; It is an accepted fact that, in many countries, pharmacies are the predominant source of medical advice over-the-counter drugs, and supplies of "prescription-only" drugs for sale without a prescription . To assess the activities conducted by pharmacists or pharmacy counter assistants in response to a common health problem, a cross-sectional study was done at 114 pharmacies in Porto Alegre, Brazil . A fictitious case-history of cough was used by trained personnel entering the pharmacy and the subsequent activities by the pharmacist or pharmacy counter assistant were analyzed . Some kind of medication was provided in 101 (88.5%) of the pharmacies . Pharmacists gave medication in 80% of pharmacies, and pharmacy assistants in 95.5% (p<0.03) . The class of medication most frequently dispensed was the expectorants (97 times, 92.4%), however, systemic antibiotics were provided in 11 pharmacies (10.5%) . Of note, the pharmacists provided antibiotics more frequently than did pharmacy assistants (p=0.016) . We conclude that pharmacy advice and symptomatic medical care (expectorants) are very common and that pharmacy assistants are more likely than pharmacists to provide medication . Of concern, when pharmacists were the drug dispensers of antibiotics which should be provided by prescription only, drugs were provided without proper diagnosis, and often in incorrect dosages . This reflects a potentially dangerous practice in need of careful evaluation, education and supervision. Infect Immun, 2000 Dec, 68(12), 6879 - 82 Expression of the nitric oxide synthase 2 gene is not essential for early control of Mycobacterium tuberculosis in the murine lung; Cooper AM et al.; The interleukin-12 and gamma interferon (IFN-gamma) pathway of macrophage activation plays a pivotal role in controlling tuberculosis . In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-gamma-activated macrophages . Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controlling Mycobacterium tuberculosis in the lung . In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals . This is in contrast to the rapid progression of disease in mice lacking IFN-gamma or a key member of the IFN signaling pathway, interferon regulatory factor 1 . Thus while IFN-gamma is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene . The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene. Infect Control Hosp Epidemiol, 2000 Oct, 21(10), 674 - 9 The burden of infection in long-term care; Strausbaugh LJ et al.; Available data, although fragmentary, indicate that infections impose a large burden on long-term-care facilities (LTCFs) in the United States . Endemic infections occur with frequencies estimated to range between 1.64 and 3.83 million per year . These estimates rival or exceed the annual tally for nosocomial infections in acute-care settings . Infections associated with outbreaks caused by respiratory, gastrointestinal, and antimicrobial-resistant pathogens burden LTCFs even further . As judged by antimicrobial use, transfers to hospital, and mortality figures, infections in LTCFs are not trivial . Moreover, annual costs associated with these infections appear to exceed $1 billion . Recognition of the burden associated with infection in LTCFs helps to identify research priorities for this rapidly growing area of healthcare. Acta Otorhinolaryngol Belg, 2000, 54(3), 373 - 90 Humoral immunodeficiency in recurrent upper respiratory tract infections . Some basic, clinical and therapeutic features; Daele J et al.; Adequate surface protection of the upper airway tract depends on intimate co-operation between natural non specific defence mechanisms such as ciliary function and acquired adaptative immunity . The latter is mediated by specific antibodies mainly belonging to secretory immunoglobulin A (SIgA) and to lesser extent secretory IgM (SigM) as well as by serum derived and locally produced IgG . Immunoglobulin's deficiency may exist in a significant percentage of patients with chronic or recurrent infections of the upper respiratory tract . So an immunologic screening should be extended to patients who have persistent sinus infection, despite normal mucocilary and ventilation patterns, inadequate response to antimicrobial therapy, culture of unusual pathogens from the upper respiratory tract or history of infection at other side, mainly bronchopulmonary . The therapeutic aspects include immunoglobulin replacement or mucosal immunogens whose efficacy is related with both an unspecific and a specific way . In the future, cytokines will probably become the strongest therapy of the immunoglobulin's deficiency. Phytomedicine, 2000 Oct, 7(5), 427 - 48 Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica; Brinkhaus B et al.; Centella asiatica is a medicinal plant that has been in use since prehistoric times . Its active constituents include pentacyclic triterpene derivatives . Studies have been conducted in particular to investigate the madecassosides and asiaticosides . In common with most traditional phytotherapeutic agents, Centella asiatica is used in folk medicine to treat a wide range of indications . In contrast to other medicinal plants, however, Centella asiatica has been subjected to quite extensive experimental and clinical investigations . Studies done in accordance with standardized scientific criteria have shown it to have a positive effect in the treatment of venous insufficiency and striae gravidarum . Centella asiatica also appears to be effective in the treatment of wound healing disturbances . At the present time, clinical studies aimed at investigating the sedative, analgesic, antidepressive, antimicrobial, antiviral and immunomodulatory effects that have been demonstrated experimentally, are still lacking . However, the therapeutic potential of this plant in terms of its efficacy and versatility is such that further detailed research would appear worthwhile. Structure Fold Des, 2000 Oct 15, 8(10), 1049 - 58 Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution; Blaszczyk J et al.; BACKGROUND: Folates are essential for life . Unlike mammals, most microorganisms must synthesize folates de novo . 6-Hydroxymethyl-7, 8-dihydropterin pyrophosphokinase (HPPK) catalyzes pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate pathway, and therefore is an ideal target for developing novel antimicrobial agents . HPPK from Escherichia coli is a 158-residue thermostable protein that provides a convenient model system for mechanistic studies . Crystal structures have been reported for HPPK without bound ligand, containing an HP analog, and complexed with an HP analog, two Mg(2+) ions, and ATP . RESULTS: We present the 1.25 A crystal structure of HPPK in complex with HP, two Mg(2+) ions, and AMPCPP (an ATP analog that inhibits the enzymatic reaction) . This structure demonstrates that the enzyme seals the active center where the reaction occurs . The comparison with unligated HPPK reveals dramatic conformational changes of three flexible loops and many sidechains . The coordination of Mg(2+) ions has been defined and the roles of 26 residues have been derived . CONCLUSIONS: HPPK-HP-MgAMPCPP mimics most closely the natural ternary complex of HPPK and provides details of protein-substrate interactions . The coordination of the two Mg(2+) ions helps create the correct geometry for the one-step reaction of pyrophosphoryl transfer, for which we suggest an in-line single displacement mechanism with some associative character in the transition state . The rigidity of the adenine-binding pocket and hydrogen bonds are responsible for adenosine specificity . The nonconserved residues that interact with the substrate might be responsible for the species-dependent properties of an isozyme. Fitoterapia, 2000 Dec, 71(6), 710 - 2 Antimicrobial activity of flowers from Anthemis cotula; Quarenghi MV et al.; The flavonoid containing total extract of Anthemis cotula flowers, tested at the concentration of 200 microg/ml, showed interesting antimicrobial activity against both Gram-negative and Gram-positive microorganisms. Fitoterapia, 2000 Dec, 71(6), 704 - 6 Antimicrobial activity and cytotoxicity of Trapa bispinosa; Rahman MM et al.; The extracts of Trapa bispinosa showed interesting antimicrobial activity against Gram-positive and Gram-negative test organisms and significant cytotoxic activity. Trop Doct, 2000 Oct, 30(4), 197 - 200 The incidence of Legionella pneumophila: a prospective study in a tertiary care hospital in India; Chaudhry R et al.; The prevalence of Legionella pneumophila causing community-acquired pneumonia (CAP) in patients who were admitted to hospital was investigated . Between April 1997 and December 1998, 60 patients admitted to the All India Institute of Medical Sciences with CAP, were included in the study . Aetiological diagnosis was based on the results of routine microbiological blood culture for bacteria and serological test by enzyme linked immunosorbent assay (ELISA) for L . pneumophila serogroup 1-7 . Eight (13%) patients had a conventional bacterial aetiology and nine (15%) had serological evidence of recent infection with L . pneumophila . Legionella pneumophila may be an important cause of CAP in adults in developing countries . Empiric antimicrobial treatment should include a combination of agents to cover both atypical agents and bacterial pathogens. Health Technol Assess, 2000, 4(21), 1 - 237 Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration; O'Meara S et al.; BACKGROUND: Chronic wounds, including pressure sores, leg ulcers, diabetic foot ulcers and other kinds of wounds, healing by secondary intention are common in both acute and community settings . The prevention and treatment of chronic wounds includes many strategies, including the use of various wound dressings, bandages, antimicrobial agents, footwear, physical therapies and educational strategies . This review is one of a series of reviews, and focuses on the prevention and treatment of diabetic foot ulcers and the role of antimicrobial agents in chronic wounds in general . OBJECTIVES: To assess the clinical- and cost-effectiveness of (1) prevention and treatment strategies for diabetic foot ulcers and (2) systemic and topical antimicrobial agents in the prevention and healing of chronic wounds . METHODS - DATA SOURCES: Nineteen electronic databases were searched, including MEDLINE, CINAHL, Embase and the Cochrane Library . Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched . An expert panel was consulted . METHODS - STUDY SELECTION: Randomised and non-randomised trials with a concurrent control group, which evaluated any intervention for the prevention or treatment of diabetic foot ulcers, or systemic or topical antimicrobials for chronic wounds (diabetic foot ulcers, pressure ulcers, leg ulcers of various aetiologies, pilonidal sinuses, non-healing surgical wounds, and cavity wounds) and used objective measures of outcome such as: (1) development or resolution of callus; (2) incidence of ulceration (for diabetic foot ulcer prevention studies); (3) incidence of pressure sores (pressure sore prevention studies); (4) any objective measure of wound healing (frequency of complete healing, change in wound size, time to healing, rate of healing); (5) ulcer recurrence rates; (6) side-effects; (7) amputation rates (diabetic foot ulcer treatment studies); (8) healing rates and recurrence of disease, among others, for pilonidal sinuses . Studies reporting solely microbiological outcomes were excluded . Decisions on the inclusion of primary studies were made independently by two reviewers . Disagreements were resolved through discussion . Data were extracted by one reviewer into structured summary tables . Data extraction was checked independently by a second reviewer and discrepancies resolved by discussion . All included studies were assessed against a comprehensive checklist for methodological quality . INCLUDED STUDIES - DIABETIC FOOT ULCERS: Thirty-nine trials which evaluated various prevention and treatment modalities for diabetic foot ulcers: footwear (2), hosiery (1), education (5), screening and foot protection programme (1); podiatry (1) for the prevention of diabetic foot ulcers; and footwear (1), skin replacement (2), hyperbaric oxygen (2), ketanserin (3), prostaglandins (3), growth factors (5), dressings and topical applications (9), debridement (2) and antibiotics (2) for the treatment of diabetic foot ulcers . INCLUDED STUDIES - ANTIMICROBIALS: Thirty studies were included, 25 with a randomised design . There were nine evaluations of systemic antimicrobials and 21 of topical agents . QUALITY OF STUDIES: The methodological and reporting quality was generally poor . Commonly encountered problems of reporting included lack of clarity about randomisation and outcome measurement procedures, and lack of baseline descriptive data . Common methodological weaknesses included: lack of blinded outcome assessment and lack of adjustment for baseline differences in important variables such as wound size; large loss to follow-up; and no intention-to-treat analysis . RESULTS - PREVENTION OF DIABETIC FOOT ULCERS: There is some evidence (1 large trial) that a screening and foot protection programme reduces the rate of major amputations . The evidence for special footwear (2 small trials) and educational programmes (5 trials) is equivocal . A single trial of podiatric care reported a significantly greater reduction in callus in patients receiving podiatric care . RESULTS - TREATMENT OF DIABETIC FOOT ULCERS: Total contact casting healed significantly more ulcers than did standard treatment in one study . There is evidence from 5 trials of topical growth factors to suggest that these, particularly platelet-derived growth factor, may increase the healing rate of diabetic foot ulcers . Although these studies were of relatively good quality, the sample sizes were far too small to make any definitive conclusions, and growth factors should be compared with current standard treatments in large, multicentre studies . Topical ketanserin increased ulcer healing rate in 2 studies, while systemic hyperbaric oxygen therapy reduced the rate of major amputations in 1 study . Preliminary research into the effects of iloprost and prostaglandin E1 (PGE1) on diabetic foot ulcer healing suggests possible benefits . However, good quality, large-scale confirmatory research is needed . (ABSTRACT TRUNCATED) Eur J Obstet Gynecol Reprod Biol, 2000 Dec, 93(2), 193 - 7 Wound complications in patients with carcinoma of the vulva . Comparison between radical and modified vulvectomies; Leminen A et al.; OBJECTIVE: To evaluate complications after different vulvectomies performed because of vulvar cancer . STUDY DESIGN: Retrospective analysis of 149 patients who underwent vulvectomy . RESULTS: Wound infections was found in 58% . Overweight, central or bilateral location of the tumor, and non-radical surgery were significant predictors of wound infections . Patients with a wound infection had more often wound breakdown (P<0.001), prolonged healing time (P<0.000), and lymphedema (P<0.001) than patients without infection . Antimicrobial prophylaxis did not prevent wound infection . Wound infections were found in 75% after radical en bloc vulvectomy (RV) and in 47% after modified vulvectomies (MV) (P<0.001) . Also wound breakdown (47 versus 20%) (P<0.001) and lymphedema (48 versus 12%) (P<0.0001) were more common in RV group than in MV group . Lymphocysts were found in 7%, and showed no association with wound infection or type of operation . The mean hospital stay was 26 days in patients with wound infection and 12 days in patients without infection, 31 days in RV group and 12 days in MV group, respectively . CONCLUSIONS: Wound infections are major determinants for both acute and late complications . Postoperative complications reduce with increasing use of modified vulvectomies. Clin Infect Dis, 2000 Nov, 31(5), 1188 - 95 Epub 2000 Nov 07. Toxoplasmosis after hematopoietic stem cell transplantation; Martino R et al.; Forty-one cases of toxoplasmosis were diagnosed in 15 European transplantation centers in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT) from 1994 through 1998 . Most patients (39 {94%}) were seropositive for Toxoplasma gondii before they underwent transplantation, and 30 (73%) had developed moderate to severe acute graft-versus-host disease before they developed toxoplasmosis . Thirty-five (85%) patients had Toxoplasma disease with evidence of organ involvement, whereas 6 (15%) patients had Toxoplasma infection, as defined by fever and a positive polymerase chain reaction (PCR) finding for T . gondii in blood . Nine patients were diagnosed at autopsy . Thirty patients (73%) had not received antimicrobial prophylaxis with anti-Toxoplasma activity after undergoing transplantation . The median day of onset of disease after HSCT was 64 . Twenty-two (63%) patients died from toxoplasmosis, and 23 (66%) received adequate anti-Toxoplasma therapy for > or =3 days . Among these 23 patients, 11 (48%) showed a complete response and 3 (13%) showed improvement . In univariate and multivariate analyses, having received adequate therapy and experiencing late infection (>63 days after HSCT) were associated with a lower risk of dying from toxoplasmosis . Toxoplasmosis after HSCT is a severe infection with a high mortality rate even when diagnosed soon after HSCT, and PCR may help establish the diagnosis earlier. J Hosp Infect, 2000 Nov, 46(3), 230 - 5 Use and misuse of antimicrobial agents in a general hospital in the AIDS era; Rivero M et al.; A prevalence study was carried out to ascertain the pattern of antimicrobial use, costs and relevance in a general hospital during the AIDS era . All patients receiving antimicrobials were studied . Antimicrobials were divided into antibacterial drugs and others and the costs evaluated in US dollars . Of 1526 patients surveyed, 455 (29.8%) were receiving 664 courses of antimicrobials: 109 (7.2%) as prophylaxis and 346 (22.6%) as treatment . Fifteen percent of courses involved non-antibacterial drugs . In 188 patients (40.9% of those treated) treatment was inadequate, usually because of incorrect drug choice . Daily cost of antimicrobials was $14953 . AIDS accounted for 3% of all patients, 9% of those receiving antimicrobials, 19.7% of antimicrobial usage and 9.6% of the antimicrobial expenditure . Misuse occurred in 43% of non-HIV patients and 17% of those with HIV . Thus, despite a disproportionate contribution of patients with AIDS, adequacy of use of antimicrobials was better in this population . Ned Tijdschr Geneeskd, 2000 Oct 21, 144(43), 2049 - 55 {Optimizing antibiotics policy in the Netherlands . V . SWAB guidelines for perioperative antibiotic prophylaxis . Foundation Antibiotics Policy Team}; van Kasteren ME et al.; The Stichting Werkgroep Antibioticabeleid (SWAB, Foundation Antibiotics Policy Team) has issued guidelines for perioperative antibiotic prophylaxis in Dutch hospitals . Antibiotic prophylaxis is generally recommended for surgical procedures with relatively high postoperative infection rates and those in which consequences of infection are really serious . Studies have revealed that prophylaxis given within two hours before incision is most effective . Short-term, preferably single-dose prophylaxis, is as effective as multiple-dose prophylaxis in most procedures . For reasons of cost effectiveness and prevention of induction of resistance, single-dose prophylaxis is recommended . The antimicrobial agent of choice for perioperative prophylaxis should not be widely used as a therapeutic agent, should be selectively active against micro-organisms most frequently isolated from surgical site infections, and should have a plasma-half-life that makes single-dosing possible for most operations . Therefore cefazoline is an agent that is widely used for perioperative prophylaxis. J Clin Periodontol, 2000 Nov, 27(11), 806 - 9 A study to assess the plaque inhibitory activity of a new triclosan mouthrinse formulation; Moran J et al.; BACKGROUND/AIMS: Toothpastes and mouthrinses containing triclosan have been shown to be of some value at inhibiting both plaque and gingivitis . However much improved activity can be obtained by the addition of other chemicals which increase substantivity or antimicrobial activity . The present study was designed to determine whether a new mouthwash formulation containing a triglyceride oil was capable of reducing plaque reformation when compared to a control rinse containing neither triclosan or oil . METHODS: A total of 24 subjects took part in a double-blind, single-centre, cross-over study in which rinses were used as the only form of oral hygiene over a 4-day period . On the 1st day of each period, the subjects were given a prophylaxis to remove all plaque and calculus deposits . A single supervised rinse was taken and subsequent 2x daily rinses over the following 3 days . 24 and 96 h after the prophylaxis, the volunteers returned to the clinic, the plaque disclosed and assessed by plaque index and area . The test procedure and wash-out phase were repeated until all of the subjects had used both rinses . RESULTS: After 24 h, a 12% reduction in plaque score and a 25% reduction in plaque area was noted for the triclosan/oil rinse compared to the control rinse; however, these reductions were not significant (p>0.05) . After 96 h, the triclosan/ oil rinse failed to produce a numerical or statistical reduction in plaque whether measured by plaque score or area . CONCLUSIONS: These findings would suggest that the triclosan/oil rinse would be of little value at inhibiting dental plaque whether used alone or as an adjunct to conventional oral hygiene measures. J Pept Sci, 2000 Oct, 6(10), 497 - 511 Antibacterial peptides isolated from insects; Otvos L Jr; Insects are amazingly resistant to bacterial infections . To combat pathogens, insects rely on cellular and humoral mechanisms, innate immunity being dominant in the latter category . Upon detection of bacteria, a complex genetic cascade is activated, which ultimately results in the synthesis of a battery of antibacterial peptides and their release into the haemolymph . The peptides are usually basic in character and are composed of 20-40 amino acid residues, although some smaller proteins are also included in the antimicrobial repertoire . While the proline-rich peptides and the glycine-rich peptides are predominantly active against Gram-negative strains, the defensins selectively kill Gram-positive bacteria and the cecropins are active against both types . The insect antibacterial peptides are very potent: their IC50 (50% of the bacterial growth inhibition) hovers in the submicromolar or low micromolar range . The majority of the peptides act through disintegrating the bacterial membrane or interfering with membrane assembly, with the exception of drosocin, apidaecin and pyrrhocoricin which appear to deactivate a bacterial protein in a stereospecific manner . In accordance with their biological function, the membrane-active peptides form ordered structures, e.g . alpha-helices or beta-pleated sheets and often cast permeable ion-pores . Their cytotoxic properties were exploited in in vivo studies targeting tumour progression . Although the native peptides degrade quickly in biological fluids other than insect haemolymph, structural modifications render the peptides resistant against proteases without sacrificing biological activity . Indeed, a pyrrhocoricin analogue shows lack of toxicity in vitro and in vivo and protects mice against experimental Escherichia coli infection . Careful selection of lead molecules based on the insect antibacterial peptides may extend their utility and produce viable alternatives to the conventional antimicrobial compounds for mammalian therapy. Lett Appl Microbiol, 2000 Oct, 31(4), 299 - 302 A note: ortho-phthalaldehyde: proposed mechanism of action of a new antimicrobial agent; Simons C et al.; Ortho-phthalaldehyde (OPA) is a new aromatic dialdehyde antimicrobial agent, the mechanism of action of which has been little studied . The aims of this paper are to examine what is currently known about its mechanism of action, to compare the action with that of a widely investigated aliphatic dialdehyde, glutaraldehyde (GTA), and to put forward a hypothesis that would, in the light of current knowledge, explain how OPA inactivates micro-organisms, including GTA-resistant Mycobacterium chelonae. Lett Appl Microbiol, 2000 Oct, 31(4), 265 - 9 Development and demonstration of RNA isolation and RT-PCR procedures to detect Escherichia coli O157:H7 gene expression on beef carcass surfaces; Berry ED; Preventing the development of pathogen resistance to processing and preservation techniques will require an understanding of the genetic mechanisms that pathogens use in situ to adapt and develop tolerance to stresses they encounter in the food environment . RNA isolation and reverse-transcription (RT)-PCR protocols were developed as tools to detect gene expression in bacteria on beef carcass surfaces . The utility of these procedures was demonstrated by detecting the expression of a selectively-inducible green fluorescent protein (GFP) gene in a plasmid-transformed strain of Escherichia coli O157:H7 inoculated onto beef carcass surface tissue . These procedures should serve as useful tools for studying the genetic responses of bacteria when exposed to antimicrobial interventions applied to food animal carcasses. Rev Med Brux, 2000 Sep, 21(4), A375 - 80 {Bacterial resistance and implications for daily practice}; Sternon J; Present and future solutions to the problem of bacterial multiple resistance involve physicians, patients and veterinarians . Their behaviour should evolve to take into account the medical and economical issues of antibiotic prescription . The clinical diagnosis requires a more rigorous assessment, based on bacteriological and rapid antigenic tests . Vaccination in both young people and the elderly, is an essential prophylactic tool, which is too often neglected . When a bacterial infection is suspected or proven, priority should be given to a targeted antimicrobial therapy with a bactericidal activity, in order to quickly eradicate pathogens . Therapies should be shorter and questionable antibio-prophylaxis should also be avoided . A watch laboratory network should provide physicians with an adequate information on local bacterial resistance patterns on a regular basis, in order to allow them adjusting their prescription. Arch Med Res, 2000 Jul-Aug, 31(4), 415 - 21 Comparison of invasive and noninvasive methods for the diagnosis and evaluation of eradication of Helicobacter pylori infection in children; Yanez P et al.; BACKGROUND: Acquisition of Helicobacter pylori infection occurs mainly during childhood . To study the events associated with H . pylori colonization in children it is important to have reliable diagnostic methods . Our objective was to validate invasive and noninvasive tests for diagnosis of H . pylori infection in children before and after antimicrobial treatment . METHODS: Before treatment, invasive rapid urease test (RUT) culture and histology, as well as the noninvasive carbon-13 urea breath test (13C-UBT) and serology were validated in 59 children . The gold standard for H . pylori infection was any of three positives of the five tests . After antimicrobial treatment culture, histology, and 13C-UBT were validated in 43 children to determine eradication . The gold standard for eradication was negative in all three tests . RESULTS: For primary diagnosis, RUT was the most sensitive and specific test, followed by 13C-UBT, which performed better than serology, culture, and histology . Concordance tests also showed that RUT and 13C-UBT performed better . For determination of eradication, 13C-UBT and histology were better than culture, which showed poor sensitivity . CONCLUSIONS: RUT performed better for primary diagnosis . However, as endoscopy might not be indicated in most children, 13C-UBT could be the test of choice for diagnosis of H . pylori infection both before and after eradication treatment. J Immunol, 2000 Nov 15, 165(10), 5773 - 9 CTL-mediated killing of intracellular Mycobacterium tuberculosis is independent of target cell nuclear apoptosis; Thoma-Uszynski S et al.; Two subsets of human CTL have been defined based upon phenotype and function: CD4(-) CD8(-) double-negative (DN) CTL lyse susceptible targets via Fas-Fas ligand interaction and CD8(+) CTL via the granule exocytosis pathway . CD8(+) CTL, but not DN CTL, can mediate an antimicrobial activity against Mycobacterium tuberculosis-infected target cells that is dependent on cytotoxic granules that contain granulysin . We investigated the role of nuclear apoptosis for the antimicrobial effector function of CD1-restricted CTL using the caspase inhibitor N:-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone . We found that DN CTL-induced target cell lysis was completely dependent on caspase activation, whereas the cytolytic activity of CD8(+) CTL was caspase independent . However, both DN and CD8(+) CTL-induced nuclear apoptosis required caspase activation . More important, the antimicrobial effector function of CD8(+) CTL was not diminished by inhibition of caspase activity . These data indicate that target cell nuclear apoptosis is not a requirement for CTL-mediated killing of intracellular M . tuberculosis. Manag Care Interface, 2000 Apr, 13(4), 83 - 8 The management of bacterial infections of the upper respiratory tract in children: pharyngitis and otitis media; Adam D; Despite changes in the activities of infectious microorganisms, particularly variations in their prevalences in different parts of the body, in clinically defined diseases, and in their susceptibilities to antibiotics, the established first-line agents for the empiric treatment of otitis media and pharyngitis are still valid . Nevertheless, a number of the newer antimicrobials have become valuable as second- and third-line medications when the first-choice drugs fail or are contraindicated . In terms of fundamental principles, the question of whether pharyngitis in children warrants routine antibiotic therapy remains unresolved; in practical terms, antibiotic treatment should be considered routinely. J Antimicrob Chemother, 2000 Sep, 46 Suppl T2, 53 - 8 Surveillance studies: how can they help the management of infection? Masterton RG. The increase in antimicrobial resistance has led to predictions of doom in the international press and to depression in the medical community . It has focused attention upon measures for fighting resistance, foremost of which is susceptibility surveillance . Until recently, global efforts at surveillance have been largely uncoordinated and random . This scene is rapidly changing with the World Health Organization (WHO), among others, leading multidisciplinary, targeted initiatives . In terms of individual surveillance programmes, much has been learned about their design . The best of these, the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC), SENTRY and the Alexander Project, involve well-defined patient and organism groups against key denominators, and use standardized, internationally recognized methods that are quality-controlled, explore susceptibility quantitatively and include investigation of resistance mechanisms . Results are rapidly returned to the user . Evidence shows that surveillance, when used to guide policies on antibiotic use and infection control, can be helpful in the fight to control the development and spread of resistance . Further work is required to demonstrate these benefits and quantify them fully. J Antimicrob Chemother, 2000 Sep, 46 Suppl T2, 39 - 52 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from Europe: comparison of antibiotic susceptibilities between countries and centre types . MYSTIC Study Group (European centres only); Goossens H; The activity of meropenem and five comparators has been studied against 7886 isolates from 29 centres in 10 European countries from 1997 to 1999 as part of the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) surveillance study . Gram-positive and Gram-negative isolates from intensive care units (ICUs), neutropenia centres, cystic fibrosis (CF) centres and general wards were investigated in Belgium (1 year), Czech Republic (2 years), Germany (3 years), Italy (3 years), Poland (2 years), Russia (2 years), Sweden (2 years), Switzerland (1 year), Turkey (1 year) and UK (3 years) . Resistance to quinolones and aminoglycosides was observed, as was resistance to the cephalosporins and penicillins via extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases . Meropenem showed good activity against the pathogens tested, particularly in CF and neutropenia centres, over the 3 year period . The overall order of potency of the six antimicrobial agents tested was: meropenem > imipenem > piperacillin/tazobactam and ciprofloxacin > ceftazidime > gentamicin . No increase in resistance to the carbapenems, to date, has been detected in any of the European centres included in this study. J Antimicrob Chemother, 2000 Sep, 46 Suppl T2, 25 - 37 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from the Americas: resistance implications in the treatment of serious infections . MYSTIC Study Group (Americas); Pfaller MA et al.; The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme aims to provide in vitro surveillance data for geographically diverse institutions where meropenem is available for use . The in vitro activity of meropenem and eight comparator antimicrobial agents against 2340 significant pathogens obtained in 1999 was assessed and compared in 14 study centres in Brazil, Mexico and the USA . Isolates were further characterized for production of extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases and carbapenemases . Carbapenems demonstrated their broad spectrum and potency, inhibiting > or = 95% of all isolates irrespective of the geographical region or centre type . The overall order of activity of the nine agents tested against all pathogens in 1999 was meropenem (96%) > imipenem (95%) > cefepime (92%) > gentamicin (89%) > piperacillin/tazobactam (88%) > ceftazidime = tobramycin (86%) > cefotaxime (84%) > ciprofloxacin (83%) . Thus far, the results from the Americas indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients . In contrast, other ESBLs, fluoroquinolones and aminoglycosides have lost activity in many institutions as a result of the selection of strains producing ESBLs or having AmpC and other resistance determinants . Carbapenem resistance was observed rarely and at a prevalence similar to those reported in earlier studies . Carbapenems appear to be a continuing reliable option for the treatment of serious nosocomial infection. J Antimicrob Chemother, 2000 Sep, 46 Suppl T2, 1 - 8 Detection of emerging resistance patterns within longitudinal surveillance systems: data sensitivity and microbial susceptibility . MYSTIC Advisory Board . Meropenem Yearly Susceptibility Test Information Collection; Jones RN; Communicating information from antimicrobial resistance surveillance study data to microbiologists and physicians can be challenging . Large amounts of data, commonly reaching millions of MICs or zone diameter endpoints, must be analysed and condensed to easily-read tables or figures . Furthermore, data must not be prejudged relative to susceptibility categories, because of the diverse nature of interpretive criteria available internationally . An attempt must be made to present results of all surveillance studies in a mode that can be reinterpreted for immediate use in different geographical areas, or used to compare future data with relative ease and high accuracy . Such data displays require peer-reviewed journals to permit greater numbers of more complex tables to present results . The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) study is a year-on-year global surveillance programme in medical centres where meropenem is available for use . We have developed a presentation strategy that expands the long-term clinical value of MYSTIC results . In addition to statistical parameters, tables of cumulative percentages or numbers of strains inhibited at each tested antimicrobial concentration will be presented . Alternative figures (Finland-o-grams) could also be used, but these generally lack precise extractable rates and require more journal space . Regardless of study design, promotion of this presentation philosophy enhances any surveillance study's value to each reader or user and facilitates application to locally appropriate interpretations . The widespread use of these analysis and presentation principles as benchmarks by various resistance studies and networks is strongly encouraged, particularly by investigations across international boundaries. Int J Pharm, 2000 Nov 4, 208(1-2), 71 - 80 Colloidal carriers for benzathine penicillin G: nanoemulsions and nanocapsules; Santos-Magalhaes NS et al.; The main purpose of this work is to formulate benzathine penicillin G nanoemulsion and nanocapsules, to evaluate their physicochemical and stabilising characteristics, and to determine their antimicrobial activity and penicillin in vitro release kinetics . Nanoemulsions were produced by the spontaneous emulsification approach and nanocapsules of poly (D,L-lactic acid-co-glycolic acid) polymer (PLGA) were prepared by the method of interfacial deposition of a pre-formed polymer . A 207+/-8 nm mean diameter nanoemulsion formulation maintained stability for more than 5 months at 4 degrees C . Stable nanocapsules with 224+/-58 nm mean diameter were obtained, which remained stabilised over 120 days at 4 degrees C . The penicillin encapsulation ratio in the nanocapsules was 85% . The in vitro release profiles indicated that penicillin released from the nanoemulsion was similar to the one observed from nanocapsules . However it can be clearly deduced from the in vitro kinetic analysis that the antibiotic cannot be protected in colloidal delivery systems . Nevertheless, stable formulations obtained in this investigation supply a potential dosage form to encapsulate more easily soluble drugs. J Anim Sci, 2000 Nov, 78(11), 2896 - 902 Growth-promoting efficacy in young pigs of two sources of zinc oxide having either a high or a low bioavailability of zinc; Mavromichalis I et al.; Commercial sources of zinc oxide (ZnO) differ widely in Zn relative bioavailability (RBV), but it is unknown whether growth-promoting efficacy in young pigs is influenced by RBV of the ZnO sources used . We compared a low-RBV (39%) ZnO manufactured by the Waelz process (W) to a high-RBV (93%) ZnO manufactured by the hydrosulfide process (HS) . Antibacterial agents were included in the diet in only one of the four trials (Exp . 4) . In Exp . 1, pigs (n = 36, 6.5 kg, 28 d of age) were randomly assigned in three replicates to receive 0, 1,500, or 3,000 mg Zn/kg from HS Zn in a 21-d growth assay . Growth rates and feed intake responded linearly (P < 0.01) to incremental doses of Zn . In Exp . 2, pigs (n = 60, 6.1 kg, 28 d of age) were randomly assigned in five replicates to receive either 0 or 1,500 mg W or HS Zn/kg during a 21-d feeding period . Growth performance was improved (P < 0.01) by the addition of ZnO . During wk 1, however, pigs receiving HS Zn grew faster (P < 0.03) than those receiving W Zn, but the difference diminished to a trend (P < 0.08) during wk 2 . Morphology of duodenal, jejunal, and ileal intestinal sections was examined at d 21 of the assay, but neither source of ZnO had an effect on crypt depth or on villus height or width . In Exp . 3, weaned pigs (n = 48, 5.4 kg, 21 d of age) were randomly assigned in four replicates to the same dietary treatments as in Exp . 2 for a 17-d growth assay . Growth performance was improved (P < 0.05) by the addition of ZnO, but no difference was detected between the two sources . In Exp . 4, pigs (n = 60, 6.2 kg, 28 d of age) were randomly assigned in five replicates to receive either 0 or 1,500 mg/kg W or HS Zn in an 11-d growth assay wherein antimicrobial agents were included in the basal diet . Growth rates during the first 6-d were improved (P < 0.06) by the addition of ZnO, with a trend (P < 0.10) for greater weight gain in pigs receiving HS than in those fed W Zn . During the entire 11-d, however, there was no difference in growth rates between pigs fed the two sources of ZnO . In conclusion, RBV of Zn in ZnO did not substantially affect the growth-promoting efficacy of ZnO in young pigs fed diets with or without antimicrobial agents. Scand J Gastroenterol, 2000 Sep, 35(9), 929 - 34 Cure of Helicobacter pylori infection after failed primary treatment: one-center results from 120 patients; Seppala K et al.; BACKGROUND: Treatment with a proton pump inhibitor (PPI) and antimicrobials cures Helicobacter pylori infection in about 90% of patients . This is a retrospective overview of our studies aiming to cure the infection in all compliant patients with failed initial therapy . METHODS: We retreated 120 (19% of 644) H . pylori-infected patients whose initial therapy had failed . The retreatments included (i) triple therapy (TT): colloidal bismuth subcitrate, metronidazole, amoxicillin (or tetracycline); (ii) quadruple therapy (QT): TT and a PPI; or (iii) high doses of both a PPI and clarithromycin combined with a further 1-3 individually selected antimicrobials . The eradication results were determined after 6-12 months . RESULTS: The 1st retreatment was successful in 70 of 120 patients . The 2nd retreatment cured 25 of the remaining 42 patients, the 3rd 13 of 17, and the 4th the last 4 patients . The cumulative eradication rate (ITT) was 93% (95% CI: 88.9%-97.9%; 8 patients withdrew after a failed 1st retreatment) and the rate was 100% in the remaining 112 patients who accepted several retreatments . The 1st retreatment with TT cured 23% (95% CI: 12%-34%) of 57 patients and QT 85% (95% CI: 74%-96%) of 41 patients who had initially undergone a failed metronidazole-based treatment . All retreatments were well tolerated . CONCLUSIONS: In this study, high doses of a PPI and clarithromycin combined with 1-3 antimicrobials according to susceptibility data proved to be the best drug combination in the cure of H . pylori infection after failed primary treatment . Giving imidazole- and bismuth-based QT (without clarithromycin) as the first-line treatment of H . pylori infection ensures that the number of failures remains low. Artif Cells Blood Substit Immobil Biotechnol, 2000 Nov, 28(6), 521 - 33 Iodinated natural rubber latex: preparation, characterisation & antibacterial activity assessment; Tyagi M et al.; Natural Rubber (NR) in both its latex and dried form was treated with iodine to make it antibacterial in nature . The NR latex was dried and washed, dissolved in toluene, iodinated and cast into films . In a different approach, NR in its latex form (emulsion) was blended with aqueous solution of povidone-iodine complex (PVP-I) and films were cast . Phase separation of PVP-I was observed in the films prepared using NR latex; whereas the film prepared using NR solution in toluene and molecular iodine were homogeneous, transparent light brown . Solubility assessment of the films revealed that unlike pure NR, the iodinated NR failed to go into solution completely . The films obtained from both the approaches were evaluated for release of iodide ions . On immersion in water, PVP-I blended latex did not retain iodine while sustained release of iodide ion was observed in case of dried NR dissolved in toluene and treated with iodine . The FT-IR spectra of the iodinated films revealed that iodine attaches covalently to the double bonds in the isoprene units of NR . The films were also evaluated for their antibacterial properties and it was observed that the films prepared from both the approaches, acquired antimicrobial properties. Can Vet J, 2000 Oct, 41(10), 777 - 85 Etiology, forms, and prognosis of gastrointestinal dysfunction resembling vagal indigestion occurring after surgical correction of right abomasal displacement; Sattler N et al.; The objectives of this study were to determine the etiology and types of vagal indigestion (VI) occurring after right displacement of the abomasum or abomasal volvulus (RDA/AV), and the prognosis for each type . Data of cows presented for RDA/AV from a retrospective (n = 288) and a prospective (n = 132) study were used . Vagal indigestion occurred in 39 and 22 cows in each study, respectively . A necropsy was performed in 29 cases . Gastric compartment dilation compatible with VI type III or IV occurred in 23 cases . An abnormal gastric wall was detected in 22 cases . Peritonitis was present in 18 cows . Vagal nerve lesions were present in 5 out of 13 cases studied . Clinical, hematological, and necropsy results suggested a classification of VI with respect to presence or absence of peritonitis . Gastric wall damage, peritonitis and vagal nerve lesions appear important in the etiology . Considering peritonitis occurrence, antimicrobial therapy appears necessary in the treatment of RDA/AV. Med J Aust, 2000 Oct 2, 173 Suppl, S48 - 50 Conjugate pneumococcal vaccines: an overview; Mulholland EK; A seven-valent conjugate pneumococcal vaccine has been shown to have dramatic efficacy against invasive pneumococcal disease and lesser efficacy against otitis media and pneumonia . This vaccine was licensed for use in infants in the United States in February 2000 and is recommended there for routine use in infants and catch-up vaccination in high-risk children . Specific regional pneumococcal vaccines are not needed; nine to 11 serotypes cover most pneumococcal disease in most parts of the world; nine- and 11-valent conjugate vaccines are currently being developed for the global market . There is evidence of serotype replacement in vaccine recipients (in both carriage and disease), which might reduce overall vaccine effectiveness . There is also evidence that vaccines may reduce rates of antimicrobial resistance in pneumococci . Studies of the burden of pneumococcal disease as well as program support are needed to assist developing countries to introduce these expensive vaccines. Med J Aust, 2000 Oct 2, 173 Suppl, S41 - 4 Efficacy and effectiveness of pneumococcal polysaccharide vaccines and their use in industrialised countries; Lehmann D; Use of pneumococcal polysaccharide vaccines remains controversial, even though clinical trials have shown their efficacy in preventing invasive disease caused by vaccine serotypes in immunocompetent adults . Retrospective studies indicate these vaccines have about 50%-80% effectiveness for preventing invasive disease caused by vaccine serotypes, although effectiveness wanes over time and with age . The elderly, people living in institutions and those with chronic cardiac or respiratory disease, alcoholism or diabetes mellitus who are in relatively good health would benefit from vaccination; a polysaccharide vaccine program in the elderly has been shown to be cost-effective . In young children, polysaccharide vaccine should be evaluated as a booster to conjugate pneumococcal vaccines, which are likely to be available soon in industrialised countries . In view of the high rates of hospitalisation and of antimicrobial resistance in pneumococci, every effort should be made to increase coverage by pneumococcal polysaccharide vaccine in Australia, according to guidelines of the National Health and Medical Research Council. Nat Biotechnol, 2000 Nov, 18(11), 1162 - 6 Transgenic plants expressing cationic peptide chimeras exhibit broad-spectrum resistance to phytopathogens; Osusky M et al.; Here we describe a strategy for engineering transgenic plants with broad-spectrum resistance to bacterial and fungal phytopathogens . We expressed a synthetic gene encoding a N terminus-modified, cecropin-melittin cationic peptide chimera (MsrA1), with broad-spectrum antimicrobial activity . The synthetic gene was introduced into two potato (Solanum tuberosum L.) cultivars, Desiree and Russet Burbank, stable incorporation was confirmed by PCR and DNA sequencing, and expression confirmed by reverse transcription (RT)-PCR and recovery of the biologically active peptide . The morphology and yield of transgenic Desiree plants and tubers was unaffected . Highly stringent challenges with bacterial or fungal phytopathogens demonstrated powerful resistance . Tubers retained their resistance to infectious challenge for more than a year, and did not appear to be harmful when fed to mice . Expression of msrA1 in the cultivar Russet Burbank caused a striking lesion-mimic phenotype during leaf and tuber development, indicating its utility may be cultivar specific . Given the ubiquity of antimicrobial cationic peptides as well as their inherent capacity for recombinant and combinatorial variants, this approach may potentially be used to engineer a range of disease-resistant plants. Regul Pept, 2000 Nov 24, 95(1-3), 87 - 92 Recombinant granulocyte colony-stimulating factor induces production of human neutrophil peptides in lung cancer patients with neutropenia; Ashitani J et al.; Human neutrophil peptides (HNPs) 1, 2 and 3 are antimicrobial peptides localized in the azurophil granules of neutrophils . We investigated the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the biosynthesis of HNPs 1-3 using a sensitive radioimmunoassay and Northern blot analysis . Seven patients with lung cancer were first treated with various anticancer agents for 3 days (days 1-3) followed by treatment with rhG-CSF (2 microgram/kg weight/day) for 7 days (days 8-14) . Chemotherapy caused neutropenia but the neutrophil count increased biphasically between days 8 and 14 . Chemotherapy did not change the baseline plasma concentration of HNPs 1-3 (74.1+/-2.1 pmol/ml) but the concentration increased from day 12, 5 days after commencement of rhG-CSF therapy, to reach a peak value of 430.8+/-57.0 pmol/ml on day 15, 1 day after the last administration of rhG-CSF . Baseline HNPs 1-3 content per neutrophil was 0.59+/-0.02 fmol, decreased to 0.30+/-0.07 fmol on day 9, then increased to 0.78+/-0.07 fmol on day 15 . Analyses of peripheral blood neutrophils by Northern blot and reverse-phase high-performance liquid chromatography showed that the amounts of HNPs 1-3 mRNA and precursors of HNPs 1-3 markedly increased in response to rhG-CSF . Our results indicate that recombinant hG-CSF does not only increase neutrophil count but stimulates HNPs 1-3 biosynthesis in neutrophils, thus enhancing the host defense system of compromised hosts with neutropenia. J Antimicrob Chemother, 2000 Nov, 46(5), 803 - 5 In vitro susceptibility of Helicobacter pylori to, and in vivo suppression by, antimicrobials used in selective decontamination of the digestive tract; van der Voort PH et al.; The incidence of bleeding related to stress ulcers is reduced in critically ill patients in whom gut decontamination has been performed; this may be a result of suppression of Helicobacter pylori infection . We determined the susceptibility of H . pylori to the applied antibiotics . In nine of 10 critically ill patients (using intravenous cefotaxime and topical polymyxin, tobramycin and amphotericin B (PTA) given by nasogastric tube) and all six volunteers (using PTA alone), H . pylori was suppressed as long as the topical antibiotics were ingested . The in vitro studies revealed that all strains were susceptible to cefotaxime and tobramycin . The strains were not susceptible to polymyxin or amphotericin B. Biochem Biophys Res Commun, 2000 Nov 2, 277(3), 575 - 80 High-level expression of antimicrobial peptide mediated by a fusion partner reinforcing formation of inclusion bodies; Lee JH et al.; A gene expression system for antimicrobial peptides, which could be effectively used for various studies or applications of the antimicrobial peptides, has been developed . To avoid the harmful effects on an expression host, Escherichia coli, the antimicrobial peptides were expressed as fusion proteins with a polypeptide F4, which is a truncated PurF fragment that highly tends to form inclusion bodies . Seven different kinds of antimicrobial peptides have been successfully expressed by this expression system and the resulting expression level of fusion proteins reached up to 30% of total cell proteins . To confirm the identity of the recombinant peptide, MSI-344 was selected as a model peptide and purified to homogeneity, and we could obtain the recombinant MSI-344 of a high purity and with a good yield, which was identical to the authentic peptide in the aspects of the chemical and antimicrobial properties . These results show that the neutral fusion partner, which reinforces the formation of inclusion bodies, could mediate a high-level expression of the antimicrobial peptides . Pulm Pharmacol Ther, 2000, 13(6), 249 - 56 Parenteral antibiotic therapy in the treatment of lower respiratory tract infections . Strategies to minimize the development of antibiotic resistance; Cazzola M et al.; Antibiotic use is often imputed for increases in the prevalence of infections due to antibiotic-resistant bacteria . Resistance depends on the variety of genotypes in the large bacterial population and also on the selective pressures that are produced along the antibiotic concentration gradients in the body . In effect, at certain selective concentrations the antibiotic eliminates the susceptible majority, leaving a selected remainder intact . Therefore, the choice of antibiotics for the treatment of lower respiratory tract infections should take into consideration not only their effectiveness but also the pharmacokinetics of each agent and its delivery schedule . In fact, the potential therapeutic efficacy of an antibiotic depends not only on its spectrum of action, but also on the concentration it reaches at the site of infection . Most infections occur in the tissues of the body rather than in the blood and that it is accepted that appropriate antibiotic therapy requires the maintenance of significant concentrations of antibiotics at the site of infection in the lung long enough to eliminate the invading pathogen . Thus, the development of dosing schedules for most antimicrobials has been based on the postulate that drug levels need to be above the minimal inhibitory concentration (MIC) at this site for most or all the dosing interval . The selection of antimicrobial resistance appears to be strongly associated with suboptimal antimicrobial exposure, defined as an AUIC(0-24)/MIC ratio of less than 100O125 . Antimicrobial regimens that do not achieve these values cannot prevent the selective pressure that leads to overgrowth of resistant bacterial subpopulations . It has been suggested that resistance can be avoided with attention to dosing, since dosing which provides an AUIC(0-24)/MIC ratio of at least 100 appears to reduce the rate of the development of bacterial resistance . Unfortunately, very different serum or lung concentration profiles can result in the same AUIC(0-24)/MIC . High doses administered sufficiently may often completely prevent any possibility of attaining a selective concentration . Alternatively, an antibiotic which has good bactericidal potency and maintains tissue and/or serum concentrations greater than the MIC or, better, minimal bactericidal concentration (MBC) throughout the dosing interval is equally effective in minimizing the development of antibiotic resistance . Expert Opin Investig Drugs, 2000 Aug, 9(8), 1815 - 27 Artemisinin drugs: novel antimalarial agents; Price RN; Artemisinin and its derivatives, artesunate and artemether, represent a new class of antimicrobial drug with potent activity against Plasmodium falciparum . Although they show excellent efficacy in both severe and uncomplicated malaria, dosage regimens still need to be optimised and pharmacokinetic profiles defined . In the treatment of uncomplicated malaria, the artemisinin drugs should be used in combination with a long acting antimalarial to protect both drugs against the emergence of resistance . In the treatment of severe malaria, parenteral artemether is at least as effective as quinine and is simpler to use . The use of rectal preparations of artesunate and artemisinin at the rural health level will facilitate early initiation of the treatment of falciparum malaria and this may reduce the proportion of patients progressing to severe disease . All of the artemisinin drugs have comparable efficacy; the choice of derivative should be based upon availability, cost and quality of the preparation . Artemisinin, artesunate and artemether are well-tolerated in both adults and children, with no evidence to date of serious clinical toxicity. Expert Opin Investig Drugs, 2000 Aug, 9(8), 1731 - 42 Protegrins: new antibiotics of mammalian origin; Bellm L et al.; Protegrins and their derivatives are a new class of peptide antibiotics based on mammalian antimicrobial peptides . Their pharmacological properties include an unusually broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi and some enveloped viruses . Preclinical and clinical studies of the lead compound, IB-367, developed for topical applications, show promise for the prevention of chemotherapy- and radiation-induced oral mucositis. Expert Opin Investig Drugs, 2000 Feb, 9(2), 263 - 72 Cholic acid derivatives: novel antimicrobials; Savage PB et al.; Mimics of squalamine and polymyxin B (PMB) have been prepared from cholic acid in hope of finding new antimicrobial agents . The squalamine mimics include the polyamine and sulphate functionalities found in the parent antibiotic, however, the positions relative to the steroid nucleus have been exchanged . The PMB mimics include the conservation of functionality among the polymyxin family of antibiotics, the primary amine groups and a hydrophobic chain . Although the squalamine and PMB mimics are morphologically dissimilar, they display similar activities . Both are simple to prepare and demonstrate broad spectrum antimicrobial activity against Gram-negative and Gram-positive organisms . Specific examples may be inactive alone, yet effectively permeabilise the outer membranes of Gram-negative bacteria rendering them sensitive to hydrophobic antibiotics . Problems associated with some of the squalamine and PMB mimics stem from their haemolytic activity and interactions with serum proteins, however, examples exist without these side effects which can sensitise Gram-negative bacteria to hydrophobic antibiotics. J Gastroenterol Hepatol, 2000 Sep, 15(9), 1007 - 17 Pooled analysis of Helicobacter pylori eradication regimes in Asia; Wang WH et al.; BACKGROUND AND AIMS: Differences in Helicobacter pylori strains and their resistance to antimicrobials between Asian and Western countries may affect the success in eradicating this bacterium . Our objective was to systematically review the regimens that have been tested in Asia . METHODS: Data on anti-H . pylori therapies reported from Asia in a large number of publications identified up to December 1998 were pooled into a few groups based on the combination of drugs used . A comparison of different groups was made by calculating the pooled eradication rates . RESULTS: Seventy-three studies with 134 treatment arms were reviewed . Pooled eradication rates of dual, triple and quadruple therapies were 61.0, 86.5 and 93.4%, respectively . Proton pump inhibitor (PPI)-based combinations were more widely used and effective, with overall eradication rates of 90.7% in triple therapy and 93.4% in quadruple therapy . Bismuth combined with tetracycline and metronidazole also showed a high eradication rate of 92.0% . CONCLUSIONS: Proton pump inhibitor-based triple therapy with either clarithromycin, amoxycillin or metronidazole was one of the most commonly used and effective anti-H . pylori triple therapy regimens in Asia . The classical triple therapy with a bismuth, tetracycline and metronidazole combination has a similar efficacy . The results of anti-H . pylori treatment in Asia are not different from those in Western countries. Pediatr Int, 2000 Oct, 42(5), 461 - 3 Child health in the new millennium; Gracey M; In today's modern, industrialized and affluent countries, like Japan and Australia, better living conditions and hygiene, plentiful nutritious food and rapid advances in biology and medical technologies have helped to bring about dramatic improvements in child health . The previous heavy burdens of infections and undernutrition have been eliminated or can now be controlled or effectively treated . In these countries, child health standards are higher than ever and expectation of life at birth is much higher than in the past . Some of the technological advances that have helped bring about this transformation are immunization, antimicrobial therapy, successful treatment of childhood leukemias, transplantation of vital organs and implementation of genetic diagnosis and gene therapy . The use of genetically modified foods and the prospects for cloning of humans are areas of intense interest and controversy . However, these advances have their disadvantages (e.g . antibiotic-induced drug resistance) . Urbanization has encouraged the 'westernization' of dietary patterns and the long-term 'lifestyle diseases' that can follow in adults . Accidents, violence and drug abuse are major problems in many parts of the world . Changes in attitudes to sexuality and the spread of HIV/AIDS is another major problem, especially in Africa and Asia . Environmental pollution and the degradation of agricultural lands, rivers and seas are also important . Ironically, standards of child health and the prospects for long life in countries like Japan are better than ever before, but social and environmental changes are presenting children and their carers with new and unanswered challenges as we enter the 21 st century and the new millennium. Biochim Biophys Acta, 2000 Oct 18, 1482(1-2), 284 - 97 Immunocalins: a lipocalin subfamily that modulates immune and inflammatory responses; Logdberg L et al.; A subset of the lipocalins, notably alpha(1)-acid glycoprotein, alpha(1)-microglobulin, and glycodelin, exert significant immunomodulatory effects in vitro . Interestingly, all three are encoded from the q32-34 region of human chromosome 9, together with at least four other lipocalins (neutrophil gelatinase-associated lipocalin, complement factor gamma-subunit, tear prealbumin, and prostaglandin D synthase) that also may have anti-inflammatory and/or antimicrobial activity . This review addresses important features of this genetically linked subfamily of lipocalins (involvement with the acute phase response, immunomodulatory and anti-inflammatory properties, the tissue localization, complex formation with other proteins and receptors, etc.) . It is likely that these proteins have evolved to be an integrated part of the body's defense system as part of the extended cytokine network . Its members exert a regulatory, dampening influence on the inflammatory cascade, thereby protecting against tissue damage from excessive inflammation . That most major mammalian allergens are lipocalins may reflect this connection of lipocalins with the immune system . We propose that this immunologically active lipocalin subset be named the 'immunocalins', signifying not only the structural homology and close genetic linkage of its members, but also their protective involvement with immunological and inflammatory processes . As immune mediators, immunocalins appear to use at least three interactive sites: the lipocalin 'pocket', binding sites for other plasma proteins, and binding sites for cell surface receptors. Proc Natl Acad Sci U S A, 2000 Nov 7, 97(23), 12723 - 8 An essential amino acid induces epithelial beta -defensin expression; Fehlbaum P et al.; Antimicrobial peptides constitute an important component of the mammalian innate immune response . Several types of antimicrobial peptides, including the beta-defensins, are produced at epithelial surfaces in response to infectious threats . Here we show that a class of small molecules, including l-isoleucine and several of its analogs, can specifically induce epithelial beta-defensin expression . This induction is transcriptional in nature and involves activation of the NF-kappaB/rel family of trans-activating factors . We hypothesize that these substances represent unique markers for the presence of pathogens and are recognized by innate immune pattern recognition receptors . Isoleucine or its analogs ultimately may have clinical utility as novel immunostimulants that could bolster the barrier defenses of mucosal surfaces. Crit Care Med, 2000 Oct, 28(10), 3456 - 64 Inadequate treatment of nosocomial infections is associated with certain empiric antibiotic choices; Kollef MH et al.; OBJECTIVE: The purpose of this study was to determine the impact of scheduled changes of antibiotic classes, used for the empirical treatment of suspected or documented Gram-negative bacterial infections, on the occurrence of inadequate antimicrobial treatment of nosocomial infections . DESIGN: Prospective observational study . SETTING: Medical (19-bed) and surgical (18-bed) intensive care units in an urban teaching hospital . PATIENTS: A total of 3,668 patients requiring intensive care unit admission were prospectively evaluated during three consecutive time periods . INTERVENTIONS: During each time period, one antibiotic class was selected for the empirical treatment of Gram-negative bacterial infections as follows: time period 1 (baseline period) (1,323 patients), ceftazidime; time period 2 (1,243 patients), ciprofloxacin; and time period 3 (1,102 patients), cefepime . MEASUREMENTS AND MAIN RESULTS: The overall administration of inad