Food Addit Contam, 2003 Mar, 20(3), 221 - 8 Antibodies to the quinolones and fluoroquinolones for the development of generic and specific immunoassays for detection of these residues in animal products; Bucknall S et al.; Several quinolone and fluoroquinolone haptens have been used to raise polyclonal antibodies exhibiting both specific and generic properties for these classes of antimicrobial compounds . The antisera have been assessed in rapid enzyme immunoassays (ELISAs) designed to exploit the specificities obtained . A direct generic ELISA for both the quinolones and fluoroquinolones has been developed that uses the cross-reactivity of an antibody raised against norfloxacin (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid) linked to ovalbumin via a secondary amine group on the piperazinyl moiety to detect nine different drugs in these classes . Specific ELISAs to ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid), enrofloxacin (1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid), flumequin (9-fluoro-6,7-dihydro-5-methyl-1-oxo-1H,5H-benzo(ij)quinolizine-2-carboxylic acid) and nalidixic acid (1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid) have also been developed with a high degree of specificity to the individual compounds . The assays measure drug residues in bovine milk and ovine kidney with an interassay relative standard deviation (s(r)) of 10.5% or less and intra-assay s(r) of 11.2% or less . Sensitivity is less than 4 microg x kg(-1) for both the generic and specific assays for all but one of the compounds tested . (Pipemidic acid (8-ethyl-5,8-dihydro-5-oxo-2-(1-piperazinyl)pyrido(2,3-d)pyrimidine-6-carboxylic acid) is detectable at 6 microg x kg(-1) in kidney.) Structure (Camb), 2003 Mar, 11(3), 329 - 38 Structural basis for the antibiotic activity of ketolides and azalides; Schlunzen F et al.; The azalide azithromycin and the ketolide ABT-773, which were derived by chemical modifications of erythromycin, exhibit elevated activity against a number of penicillin- and macrolide-resistant pathogenic bacteria . Analysis of the crystal structures of the large ribosomal subunit from Deinococcus radiodurans complexed with azithromycin or ABT-773 indicates that, despite differences in the number and nature of their contacts with the ribosome, both compounds exert their antimicrobial activity by blocking the protein exit tunnel . In contrast to all macrolides studied so far, two molecules of azithromycin bind simultaneously to the tunnel . The additional molecule also interacts with two proteins, L4 and L22, implicated in macrolide resistance . These studies illuminated and rationalized the enhanced activity of the drugs against specific macrolide-resistant bacteria. Arch Intern Med, 2003 Mar 10, 163(5), 601 - 5 Fluoroquinolone utilization in the emergency departments of academic medical centers: prevalence of, and risk factors for, inappropriate use; Lautenbach E et al.; BACKGROUND: Resistance to fluoroquinolone (FQ) antibiotics has risen markedly in recent years and has been associated with increasing FQ use; however, few data exist regarding FQ use patterns . Designing strategies to limit FQ resistance by optimizing FQ use depends on identifying patterns of inappropriate FQ use . Use of FQs in emergency departments (EDs) has not been studied . METHODS: We studied 100 consecutive ED patients who received an FQ and were subsequently discharged . Appropriateness of the indication for use was judged according to existing institutional guidelines . A case-control study was conducted to identify the prevalence of, and risk factors for, inappropriate FQ use . RESULTS: Of 100 total patients, 81 received an FQ for an inappropriate indication . Of these cases, 43 (53%) were judged inappropriate because another agent was considered first line, 27 (33%) because there was no evidence of infection based on the documented evaluation, and 11 (14%) because of inability to assess the need for antimicrobial therapy . Although the prevalence of inappropriate use was similar across various clinical scenarios, there was a borderline significant association between the hospital in which the ED was located and inappropriate FQ use . Of the 19 patients who received an FQ for an appropriate indication, only 1 received both the correct dose and duration of therapy . CONCLUSIONS: Inappropriate FQ use in EDs is extremely common . Efforts to limit emergence of FQ resistance must address the high level of inappropriate FQ use in EDs . Future studies should evaluate the impact of interventions designed to reduce inappropriate FQ use in this setting. Phytomedicine, 2003 Jan, 10(1), 59 - 61 Antimicrobial activity of various extracts and carvacrol from Lippia multiflora leaf extract; Kunle O et al.; This study examines the antimicrobial activity of the hexane, dichloromethane and methanol extracts of Lippia multiflora and carvacrol isolated from the hexane extract . The result shows the hexane extract to be the most active, while the methanol extract exhibited no antimicrobial activity . The isolated carvacrol from the hexane fraction showed tremendous antimicrobial activity . These results confirm the traditional uses of Lippia multiflora in the treatment of disease conditions due to microbes. Int J Hyg Environ Health, 2003 Jan, 206(1), 1 - 8 Home hygiene: a risk approach; Bloomfield SF; The need to place "prevention through hygiene" at the core of strategies for infection prevention has been emphasised by recent events . Indications are that re-evaluation of current practice and the promotion of improved hygiene in the domestic setting could have a significant impact in reducing infectious disease . If the public are to play a part however they must be properly informed . Encouraging the concept of the home as a setting in which the whole range of activities occur, including food hygiene, personal hygiene and hygiene related to medical care, provides the opportunity for a rational approach to home hygiene based on risk assessment . In the home surfaces (including hand surfaces) and other sites play an important part in the transmission of infection, especially food-borne infections . From an assessment of the frequency of occurrence of pathogens and potential pathogens at reservoirs, disseminators and hand and food contact sites together with the potential for transfer within the home, the risks of exposure can be assessed . This can be used to develop a rational approach in which effective hygiene procedures involving cleaning and disinfection as appropriate are targeted at these sites to reduce risks of cross contamination . This approach is consistent with the view that good home hygiene is not about "getting rid of household germs" but about targeting hygiene measures appropriately to reduce exposure to germs and thereby prevent cross infection . In motivating change, education programmes must take account of concerns related to antimicrobial resistance, the environment and the "health" of the immune system. Jpn J Antibiot, 2002 Dec, 55(6), 875 - 81 {Investigation on administration method of carbapenems}; Mikamo H et al.; Seventy-two women diagnosed as parametritis were enrolled in this study and examined on the effective administration method of carbapenems, imipenem/cilastatin (IPM/CS), panipenem/betamipron (PAPM/BP) and meropenem (MEPM) . The total dosage of each carbapenem was 1.5 g/day, and administration frequency was twice a day (0.75 g x 2) or three times a day (0.5 g x 3) . We reviewed the highest body temperature, white blood cell count and CRP value, before treatment and the fourth day after the start of treatment . Three times a day method was statistically superior to twice a day method in the highest body temperature, and CRP value . When we use carbapenem antimicrobial agents, the basis of PK/PD of time above MIC would lead to the increasing clinical effects. Jpn J Antibiot, 2002 Dec, 55(6), 771 - 7 {Comparative in vitro activities of several antimicrobial agents against Helicobacter pylori}; Sugita K et al.; Comparative in vitro activities of several antimicrobial agents against Helicobacter pylori were evaluated . Minimum inhibitory concentrations against 41 strains of H . pylori were determined by using E test . All 41 strains were isolated from gastric mucosa of patients suspected to have gastric ulcer . The ranges of MIC of amoxicillin was from 0.016 microgram/ml and less to 0.064 microgram/ml . The ranges of MIC of clarithromycin, erythromycin, and azithromycin were from 0.016 microgram/ml and less to 64 micrograms/ml, from 0.016 microgram/ml and less to more than 256 micrograms/ml, from 0.064 to more than 256 micrograms/ml, respectively . The ranges of MIC of ciprofloxacin, sparfloxacin, levofloxacin, norfloxacin were from 0.016 microgram/ml and less to 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.002 microgram/ml and less to more than 32 micrograms/ml, from 0.064 to more than 32 micrograms/ml, respectively. Clin Pharmacol Ther, 2003 Mar, 73(3), 242 - 52 Effect of single and repeated oral doses of telithromycin on cardiac QT interval in healthy subjects; Demolis JL et al.; BACKGROUND: Telithromycin is the first member of a new class of antimicrobials-the ketolides . The main objective of this study was to assess the effect of various oral doses of telithromycin on QT interval during single and repeated administrations . METHODS: Seventeen men and 17 women participated in double-blind, placebo-controlled, crossover studies . Of these subjects, 18 (9 men and 9 women) received single and repeated oral doses of telithromycin (800 mg daily), clarithromycin (500 mg twice daily), or placebo (protocol 1) . The other 16 subjects received a single oral dose (800 mg, 1600 mg, and 2400 mg) of telithromycin or placebo (protocol 2) . At the time of expected telithromycin maximum concentration, several electrocardiographic recordings were obtained at rest and during the course of a submaximal exercise test . QT intervals were measured within a wide range of R-R intervals in each subject . RESULTS: ANOVA showed that telithromycin did not increase QT interval at any dose compared with placebo . The greatest effect observed during any study period was a mean (+/-SD) change in QT-interval duration of 4.2 +/- 15.2 ms (ie, +1.2% +/- 4.0%, P not significant) at R-R = 1000 ms after repeated doses of 800 mg telithromycin . Outlier values (change in Bazett QTc from baseline >60 ms) from resting 12-lead electrocardiograms did not differ across treatment groups, including placebo . CONCLUSIONS: Telithromycin administered as repeated doses of 800 mg (recommended doses) or as single doses of up to 3 times this recommended dose did not increase the QT interval at any heart rate at rest and during effort . Telithromycin did not prolong QT-interval duration when administered to healthy young male and female subjects. Genes Immun, 2003 Mar, 4(2), 87 - 94 Toll-like receptors and their role in experimental models of microbial infection; Qureshi ST et al.; Effective host defense against microbial infection depends upon prompt recognition of pathogens, activation of immediate containment measures, and ultimately the generation of a specific and definitive adaptive immune response . The innate immune system of the host is responsible for providing constant surveillance against infection; when confronted by pathogens it deploys a series of rapidly acting antimicrobial effectors while simultaneously instructing the adaptive immune system as to the nature and context of the infectious threat . Pathogen recognition and activation of innate immunity is mediated by members of the Toll-like receptor (TLR) family through detection of conserved microbial structures that are absent from the host . Experimental models of infection using TLR-deficient mice, as well as limited human studies, have clearly demonstrated the critical role of TLRs in host defense against most major groups of mammalian pathogens. Chem Biol, 2003 Feb, 10(2), 189 - 96 Broad-spectrum peptide inhibitors of aminoglycoside antibiotic resistance enzymes; Boehr DD et al.; The action of aminoglycoside antibiotics is inhibited by chemical modification catalyzed by aminoglycoside inactivating enzymes, which bind these cationic saccharides with active site pockets that contain a preponderance of negatively charged residues . In this study, it was observed that several cationic antimicrobial peptides, representing different structural classes, could serve as inhibitors of such aminoglycoside resistance enzymes . The bovine antimicrobial peptide indolicidin and synthetic analogs appeared to be especially effective against a range of resistance enzymes, inhibiting enzymes belonging to both aminoglycoside phosphotransferase and aminoglycoside acetyltransferase classes, where the mode of action was dependent on the class of antibiotic resistance enzyme . These peptides represent the first example of broad-spectrum inhibitors of aminoglycoside resistance enzymes. Biochem J, 2003 May 1, 371(Pt 3), 663 - 8 Induction of ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptides by bacterial injection: novel members of ASABF in the nematode Ascaris suum; Pillai A et al.; Recently, invertebrate models have been widely used for the study of innate immunity . Nematodes are novel potential candidates because of the experimental advantages of Caenorhabditis elegans . However, whether nematodes have active immune responses is still ambiguous . Previously, we reported ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptides in the parasitic nematode Ascaris suum and the genetic model nematode C . elegans . Further screening of a cDNA library and an expressed-sequence-tag database search detected five novel members of ASABF (ASABF-beta, -gamma, -delta, - epsilon and -zeta) in A . suum . The transcripts for ASABF-alpha, -beta, -gamma, and -delta clearly increased in the body wall, and also in the intestine for ASABF-delta, 4 h after injection of heat-killed bacteria into the pseudocoelom (body cavity), suggesting that these peptides are inducible in the acute phase of immune response . These results also suggest that the nematodes can recognize bacteria in the pseudocoelomic fluid and evoke an active immune response. Med Trop (Mars), 2002, 62(5), 554 - 60 {Treatment of malaria in children: 1 . Uncomplicated malaria}; Imbert P et al.; Malaria is a worldwide epidemic causing high morbidity and mortality especially in children younger than 5 years . In France the incidence of pediatric malaria has constantly increased up to 1500 cases in the last two years, due to Plasmodium falciparum in more than 80% of cases . According to current recommendations, any patient with clinical suspicion or confirmed diagnosis of malaria must be hospitalized for treatment . Halofantrine is the most widely used antimalarial for treatment of uncomplicated P . falciparum malaria in children . However due to halofontrine-related cardiotoxicity some teams recommend mefloquine as the first-line drug despite disadvantages related to its poorly adapted formulation and adverse gastrointestinal effects in young children . Treatment of malaria involving other plasmodium species is still based on chloroquine . Likewise the World Health Organization continues to recommend chloroquine as the first-line agent for uncomplicated malaria in endemic zones with moderate chloroquine resistance . Amodiaquin or sulfadoxine-pyrimethamine combination may be used either in case of failure or as first-line agents in zones with high chloroquine resistance . In case of multiple resistance, quinine may be used alone or in association with an antimicrobial . Other drug therapies such as combinations using artemisinine derivatives have been shown to be highly effective for control of clinical symptoms and parasitemia . Widespread use of these therapies to prevent the appearance and extension of resistance is now undergoing evaluation. Laryngoscope, 2003 Mar, 113(3), 432 - 5 Expression of a cathelicidin antimicrobial peptide is augmented in cholesteatoma; Jung HH et al.; OBJECTIVES/HYPOTHESIS: Antimicrobial peptides are active defense components of innate immunity . Their importance was confirmed at epithelial surfaces as immediate barrier effectors in preventing infection . Cathelicidins are peptide antibiotics that are receiving increasing attention . Several studies have shown that overexpression of cathelicidin results in augmented protection against bacterial infection and prevention of local infection and systemic invasion of microbes . The goal of the study was to investigate whether cathelicidin is upregulated in cholesteatoma epithelium compared with normal skin . STUDY DESIGN: Twenty patients from a prospective study of cholesteatoma tissues and normal skins were enrolled in the study . The specimens were divided into two portions . One portion was used for subsequent RNA studies; the other was used for immunohistochemical staining . METHODS: Reverse transcriptase-polymerase chain reaction was used to assess the expression levels of cathelicidin messenger RNA (mRNA) both in cholesteatoma and in normal skin . Presumptive concentration of cathelicidin mRNA and beta2-microglobulin mRNA was evaluated . Ratio of beta2-microglobulin to cathelicidin was analyzed in each group . The expressions of cathelicidin in cholesteatoma and normal skin epithelium were investigated by an immunohistochemical technique . RESULTS: Cathelicidin mRNA in cholesteatoma epithelium was increased 5.5-fold compared with normal skin of the ear canal . In cholesteatoma epithelium, cathelicidin was located in all the layers, but in the normal skin it was expressed only in the granular and prickle cell layers . CONCLUSIONS: Cathelicidin is augmented in cholesteatoma epithelium, and the data in the present study are in agreement with the hypothesis that cathelicidin is likely to act as a key component in the first line of defense at the surface epithelium. J Antimicrob Chemother, 2003 Mar, 51(3), 545 - 56 Relative contributions of the AcrAB, MdfA and NorE efflux pumps to quinolone resistance in Escherichia coli; Yang S et al.; Quinolones are widely used, broad-spectrum antimicrobial agents . In screens for genes that, when overexpressed, allow Escherichia coli to grow on otherwise lethal concentrations of the fluoroquinolone norfloxacin, the ydhE gene was identified . We have shown that ydhE encodes a multidrug efflux pump with a narrower substrate range than that of its closest homologue, encoded by norM, and named the gene norE . The relative contributions to drug resistance of NorE compared with the two other known E . coli quinolone pumps, AcrAB and MdfA, have been defined . Overexpression of each of the three pumps separately resulted in roughly similar levels of quinolone resistance, whereas simultaneous overexpression of norE or mdfA in combination with acrAB gave synergic increases in quinolone resistance . The level of quinolone resistance mediated by efflux pumps seems to be constrained to an approximately 10-fold maximum, even with increased production of the pumps . We measured the drug resistance of an isogenic set of strains containing the various permutations of single, double and triple drug efflux pump mutants . The DeltanorE and DeltamdfA mutants were somewhat more susceptible to fluoroquinolones than the parent strain, and acrAB mutants were four- to six-fold more susceptible . Mutants lacking two or all three efflux pumps were not significantly more susceptible to fluoroquinolones than those lacking only one of the three pumps. J Antimicrob Chemother, 2003 Mar, 51(3), 497 - 511 Drugs of the 21st century: telithromycin (HMR 3647)--the first ketolide; Ackermann G et al.; Telithromycin (HMR 3647) is the first ketolide introduced into clinical practice . Ketolides are semisynthetic derivates of erythromycin A that carry novel biological properties on the erythronolide A ring . This new class of antimicrobials was designed to overcome current resistance mechanisms against erythromycin A within Gram-positive cocci . Ketolides do not induce macrolide-lincosamide-streptogramin B (MLS(B)) resistance and are active against erythromycin resistance methylase gene (erm)-carrying Gram-positive cocci . This review summarizes published data on telithromycin and intends to define the challenge that a new antimicrobial brings to medical practice. Int J Antimicrob Agents, 2003 Feb, 21(2), 135 - 42 Impact of travel on international spread of antimicrobial resistance; Memish ZA et al.; Antimicrobial resistance, an escalating problem worldwide, affects a broad range of human diseases . Excessive and inappropriate drug usage is the key driver for the emergence of resistant organisms . Travel, trade and mass migration form an important mode for their spread . The use of molecular biology provides the means of understanding the genesis and spread of the genes for drug resistance . Antimicrobial use in veterinary practice as food additives causes selection of resistant zoonotic pathogens that may spread to humans . Comprehensive surveillance systems should be designed and implemented at local and national levels and a national resistance surveillance database operationalized . There is also need for better regulation of the use of antibiotics and education of the medical fraternity, veterinarians and the public in the appropriate use of antimicrobials. Mol Biochem Parasitol, 2003 Mar, 127(1), 23 - 35 Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides; Bera A et al.; We demonstrate that antimicrobial peptides induce an autophagic cell death in the protozoan pathogen, Leishmania donovani . In our study, three antimicrobial peptides, Indolicidin, and two peptides derived from Seminalplasmin exhibit antileishmanial activity with a 50% lethal dose of 3.5 x 10(-5), 3.8 x 10(-4) and 1.7 x 10(-8) microM, respectively . The action of these antimicrobial peptides on the Leishmania cell involves ionic interactions, which are modulated by lipophosphoglycan on the parasite's surface . Peptide treatment caused dissipation of membrane potential and equilibration of intracellular pH with extracellular environment . However, there was no release of intracellular GFP molecules upon peptide treatment of a GFP expressing Leishmania clone . Transmission electron microscopic studies show extensive intracellular damage including cytoplasmic vacuolization and degeneration of cellular organization without disruption of the plasma membrane . These peptides induce cell death via a non-apoptotic process as shown by lack of nuclear fragmentation or DNA laddering and independent of caspase-like activity . Instead, Monodansylcadaverine (MDC), a biochemical marker of autophagy specifically labels the vacuoles induced by peptides . Collectively, these results indicate that in addition to their effects on the leishmanial membrane, these antimicrobial peptides induce pathway(s) for autophagic cell death in L . donovani. Mol Biochem Parasitol, 2003 Feb, 126(2), 129 - 42 Fatty acid and sterol metabolism: potential antimicrobial targets in apicomplexan and trypanosomatid parasitic protozoa; Roberts CW et al.; Current treatments for diseases caused by apicomplexan and trypanosomatid parasites are inadequate due to toxicity, the development of drug resistance and an inability to eliminate all life cycle stages of these parasites from the host . New therapeutics agents are urgently required . It has recently been demonstrated that type II fatty acid biosynthesis occurs in the plastid of Plasmodium falciparum and Toxoplasma gondii and inhibitors of this pathway such as triclosan and thiolactomycin restrict their growth . Furthermore, Trypanosoma brucei has recently been demonstrated to use type II fatty acid biosynthesis for myristate synthesis and to be susceptible to thiolactomycin . As this pathway is absent from mammals, it may provide an excellent target for novel antimicrobial agents to combat these diverse parasites . Leishmania and Trypanosoma parasites produce ergosterol-related sterols by a biosynthetic pathway similar to that operating in pathogenic fungi and their growth is susceptible to sterol biosynthesis inhibitors . Thus, inhibition of squalene 2,3-epoxidase by terbinafine, 14alpha-methylsterol 14-demethylase by azole and triazole compounds and delta(24)-sterol methyl transferase by azasterols all cause a depletion of normal sterols and an accumulation of abnormal amounts of sterol precursors with cytostatic or cytoxic consequences . However, Leishmania parasites can survive with greatly altered sterol profiles induced by continuous treatment with low concentrations of some inhibitors and they also have some ability to utilise and metabolise host sterol . These properties may permit the parasites to evade treatment with sterol biosynthesis inhibitors in some clinical situations and need to be taken into account in the design of future drugs . Rev Med Interne, 2003 Jan, 24(1), 17 - 23 {Lemierre's syndrome: a report of six cases}; Pulcini C et al.; OBJECTIVE: Lemierre's syndrome is a rare but severe condition combining pyrexia, cervical pain and pulmonary signs following a pharyngeal infection, usually tonsillitis . This infectious disease is still present in our country despite wide use of antibiotic therapy in pharyngeal infections . METHODS: In a retrospective study conducted between 1995 and 2000 in two departments (infectious diseases and critical care unit) of Nice university hospital (Nice, France), we collected and analysed six cases of Lemierre's syndrome . RESULTS: We describe a serie of 6 cases, all of them female patients of mean age 27 . We enrolled healthy patients whose initial symptom was tonsillitis . Most of these patients showed signs of severe sepsis and one died of septic shock . All the others recovered with treatment . The mean time between tonsillitis and first sign of sepsis was seven days . In four cases, patients received a beta- lactam antimicrobial agent with metronidazole . In two cases, patients were treated with amoxicillin-clavulanate . All patients were investigated for the presence of internal jugular vein thrombosis and were treated by anticoagulants when research was positive . CONCLUSIONS: A strong presumptive diagnosis can be made on the basis of clinical presentation, secondarily confirmed by para-clinical data . The prognosis depends on the speed and quality of management . We therefore wished to raise awareness of this condition among our colleagues by reporting our personal experience. Lancet Infect Dis, 2003 Mar, 3(3), 156 - 61 Impact of current transplantation practices on the changing epidemiology of infections in transplant recipients; Singh N; The spectrum of infections in transplant recipients has been substantially affected by novel immunosuppressive regimens and the use of antimicrobial agents . Epidemiology and presentation of traditional opportunistic pathogens has changed . Invasive aspergillosis and cytomegalovirus occur later in the post-transplant period . The incidence of infections that were previously encountered rarely--eg, BK virus nephropathy--has increased, the clinical course of hepatitis C virus recurrence has become more aggressive, the risk factors for invasive aspergillosis have changed, and non-aspergillus moulds are occurring more commonly in transplant recipients . Recognition of these trends as they unfold has significant implications for the clinical care of the transplant recipients, for providing insights into the pathogenesis, and for continually improving the approaches to the management of infections. Expert Opin Pharmacother, 2003 Mar, 4(3), 369 - 84 Current pharmacotherapy for the treatment of severe burns; Murphy KD et al.; The pharmacotherapy of burn care has evolved from the first topical antibiotics instituted > 30 years ago . These have helped greatly to reduce the incidence of burn wound sepsis, but a better understanding of the principles of burn care has resulted in earlier burn wound excision and complete coverage with autograft, cadaver skin, synthetic dressings, and amnion . This has markedly reduced septic complications and ameliorated the hypermetabolic response to burn injury . The hypermetabolic response, which is mediated by hugely increased levels of circulating catecholamines, prostaglandins, glucagon and cortisol, causes profound skeletal muscle catabolism, immune deficiency, peripheral lipolysis, reduced bone mineralisation, reduced linear growth, and increased energy expenditure . Supportive therapy and pharmacological manipulation, acutely and during rehabilitation, with growth hormone, insulin and related proteins, oxandrolone and propranolol can ameliorate the hypermetabolic response, improving survival and long-term outcome . Despite judicious use of topical and systemic antibiotics, opportunistic nosocomial bacterial resistance threatens to annul the improved survival of patients with severe burns . Patterns of emerging resistance encountered in burn units need to be considered, in light of a decreasing antibiotic armamentarium . A holistic approach to pharmacotherapy of severely burned patients including current practice in antimicrobial control, analgesia, sedation, and anxiety management is required . Current therapy of frequently encountered problems, such as post-burn pruritus, prophylaxis of deep venous thrombosis and peptic ulceration, and pharmacological manipulation of inhalation injury in the burned patient is described . Current pharmacotherapy to ameliorate psychosocial problems associated with burns such as acute stress disorder, depression and post traumatic stress disorder are discussed . Better analgesics, newer antibiotics and immune stimulating drugs are required to reduce mortality and morbidity in large burns. Rev Soc Bras Med Trop, 2002 Nov-Dec, 35(6), 661 - 3 Epub 2003 Feb 26. {Typhoid fever: relapse due to antimicrobial resistance . Case report}; Alecrim WD et al.; We report for the first time in the Brazilian Amazon a typhoid fever patient with clinical and laboratorial resistance to chloramphenicol, drug of election for this disease in our region . The relapse was observed at the 7th day after the end of treatment and the patient was treated with ciprofloxacin. Altern Med Rev, 2003 Feb, 8(1), 28 - 42 Can CAM therapies help reduce antibiotic resistance? MacKay D. The Centers for Disease Control and Prevention (CDC) reported the consumption of 235 million doses of antibiotics in 2001 . It is estimated that 20-50 percent of these were unnecessarily prescribed for viral infections . Bacteria that antibiotics have controlled in the past are increasingly developing resistance to these drugs . Today, virtually all important bacterial infections in the United States and throughout the world are becoming resistant . For this reason, antibiotic resistance is among the CDC's top concerns . A large portion of antibiotics are dispensed by pediatricians treating common outpatient infectious diseases . The overuse of antimicrobials is beginning to be discouraged as scientific evidence is emerging to support the use of other therapies . In pediatric practice an emphasis on accurate diagnoses, control of environmental risk factors, and utilization of complementary and alternative medicine (CAM) therapies could reduce antibiotic prescribing . Antibiotic resistance poses a growing threat to health . CAM therapies may provide a safer, more effective treatment for many acute infections of childhood. Rev Med Suisse Romande, 2002 Dec, 122(12), 606 - 11 {Ambulatory parenteral antibiotics in the treatment of severe pediatric infections}; Krahenbuhl JD et al.; The indications to parenteral antibiotic treatment in paediatrics are frequent . Antibiotic agents with antimicrobial spectrums and pharmacodynamic properties allowing effective and secure outpatient parenteral therapy are now widely available . Outpatient treatment has a number of advantages including important economic benefits . The physician responsible for conducting such treatment should select patients according to strict criteria and never neglect security and quality issues . In this article, the authors discuss different aspects (general, medical, psychosocial, economic and practical) related to outpatient parenteral antibiotic treatment of severe paediatric infections. Eur J Gastroenterol Hepatol, 2003 Mar, 15(3), 313 - 5 The effect of non-pathogenic Escherichia coli in symptomatic uncomplicated diverticular disease of the colon; Fric P et al.; BACKGROUND: The effect of probiotics in symptomatic uncomplicated diverticular disease of the colon has not been followed . DESIGN: Treatment (T1) with an intestinal antimicrobial (dichlorchinolinol) and absorbent (active coal tablets) was compared with the same set-up supplemented with non-pathogenic Escherichia coli(T2) in a prospective open trial . SETTING: The study was performed at the outpatient department of a tertiary centre . PARTICIPANTS: Fifteen subjects (5 males, 10 females) aged 68-91 years (average 74.8 years) presented with abdominal pain, irregular defecation, bloating and excessive flatulence . Diagnosis was established with colonoscopy, double-contrast barium enema, or both . INTERVENTIONS: The T1 regimen was administered for 1 week . In the T2 regimen, the application of E . coli strain Nissle (Mutaflor capsules, 2.5 x 10(10) viable bacteria/capsule) followed immediately after T1 for an average of 5.2 weeks . MAIN OUTCOME MEASURES: The lengths of two successive remissions with the T1 set-up were compared with the length of remission after T2 . The intensity of symptoms before and after administration of the probiotic was also evaluated.RESULTS The lengths of two successive remissions after T1 amounted to 2.66 and 2.20 months (average 2.43 months) . The average length of remission after T2 was 14.1 months (P < 0.001) . All symptoms after T2 decreased significantly (P < 0.001) . CONCLUSIONS: Non-pathogenic strain Nissle significantly prolonged the remission period and improved the abdominal syndrome in symptomatic uncomplicated diverticular disease . A randomized, placebo-controlled study is recommended. Microbiol Res, 2003, 158(1), 77 - 81 Combat of iron-deprivation through a plant growth promoting fluorescent Pseudomonas strain GRP3A in mung bean (Vigna radiata L . Wilzeck); Sharma A et al.; Microorganisms and plants sustain themselves under iron-deprived conditions by releasing siderophores . Among others, fluorescent pseudomonads are known to exert extensive biocontrol action against soil and root borne phytopathogens through release of antimicrobials and siderophores . In this study, production and regulation of siderophores by fluorescent Pseudomonas strain GRP3A was studied . Among various media tested, standard succinate medium (SSM) promoted maximum siderophore production of 56.59 mg l(-1) . There were low levels of siderophore in complex media like King's B medium, trypticase soya medium and nutrient medium (41.27, 29.86 and 27.63 mg l(-1)), respectively . In defferrated SSM, siderophore level was quantified to be 68.74 mg l(-1) . Supplementation with iron (FeCl3) resulted in decreased siderophore levels depending on concentration . Siderophore production was promoted by Zn2+ (78.94 mg l(-1)), Cu2+ (68.80 mg l(-1)) whereas Co2+ (57.33 mg l(-1)) and Fe3+ reduced siderophore production (37.44 mg l(-1) as compared to control (55.97 mg l(-1)) . Strain GRP3A showed plant growth promotion under iron limited conditions. Shokuhin Eiseigaku Zasshi, 2002 Oct, 43(5), 306 - 11 {Effects of veterinary drugs on beta-hexosaminidase release from rat basophilic leukemia cells (RBL-2H3)}; Tanaka Y et al.; Little is known about the effects of residual veterinary drugs on the allergic reaction, except for the antigenicity of antibiotics and synthetic antimicrobials . Therefore, 59 kinds of veterinary drugs were investigated for their effects on the IgE receptor-mediated beta-hexosaminidase release from RBL-2H3 cells as an index of immediate allergic reaction . We found that the antibiotics chlorotetracycline, doxycycline, monensin, the synthetic antimicrobial pyrimethamine and the steroid hormone testosterone inhibited beta-hexosaminidase release . Most of the veterinary drugs showed no action, though the ionophores lasalocid, salinomycin and the steroid hormone hexestrol promoted beta-hexosaminidase release from injured cells . Based on the residual levels of these drugs and the frequencies of detection in actual food samples, it seems unlikely that these drugs have any immediate allergic effect in practice. Nippon Rinsho, 2003 Jan, 61(1), 129 - 36 {Tailor-made medicine in Helicobacter pylori eradication therapy}; Aoyama N et al.; Pharmacokinetic profiles of omeprazole and lansoprazole were well correlated with the CYP2C19 genotype . The heterozygous extensive metabolizer was slightly different from the homozygote, but there was no statistically significant difference . The CYP2C19 genotype dependence found for lansoprazole was not obvious compared with omeprazole . As for rabeprazole, the pharmacokinetic profile was independent of the CYP2C19 genotype . CYP2C19 genotyping can provide a new strategy to choose an optimal regimen, and this genotyping is especially useful for Japanese, as the frequency of poor metabolizers is five times greater than that found among Caucasians . However, we should be aware that the increase of antimicrobial-resistant strains of H . pylori may force us to examine antimicrobial susceptibility of all patients in order to achieve a more than 80% eradication rate at first-line therapy in the near future . We should also have proper knowledge of the influence of the CYP2C19 genetic polymorphism on treatment efficacy according to the variety of PPI and the combination with other drugs. Nippon Rinsho, 2003 Jan, 61(1), 113 - 8 {A strategy for second-line anti-Helicobacter pylori therapy in eradication-failure patients}; Hojo M et al.; Although available H . pylori eradication regimens in Japan fail to cure 10-20% of patients, an optimal re-treatment therapy for eradication-failure patients has still not been established . Since patient compliance, bacterial resistance and genotypic differences in CYP2C19 influence the eradication rate, re-eradication therapy should be selected, taking them into consideration . In the West, meta-analysis of the second-line treatment of H . pylori infection showed therapies comprising ranitidine bismuth and two antimicrobials are very effective re-treatment therapies irrespective of factors influencing H . pylori eradication . However ranitidine bismuth is not available in Japan and re-eradication therapy consisting of PPI, amoxicillin and metronidazole have been often undertaken and have achieved high eradication rate, even including patients with metronidazole resistant H . pylori. Nippon Rinsho, 2003 Jan, 61(1), 79 - 83 {The antimicrobial susceptibility test of Helicobacter pylori}; Takahashi S et al.; Now that treatment of H . pylori associated disease is becoming common in Japan, drug resistant--H . pylori has emerged as a problem to be solved . There is no standard method of H . pylori drug susceptibility test in Japan yet . There are several methods available: Disk test, E-test, microplate method and agar plate dilution method . The E-test is being the standard method in European countries and USA . However the microplate method has been reported as a same accuracy as the agar dilution method, and thought as being a new standard method in Japan . In 2000, The Japanese Society of Chemotherapy proposed that drug susceptibility test be standardized and listed the break point of MIC of amoxicillin(AMPC) and clarithromycin(CAM). Farm Hosp, 2003 Jan-Feb, 27(1), 31 - 7 {Evolution of antimicrobial use during the years 1996-2000 in a general hospital . A detailed ICU study}; Hermosilla Najera L et al.; PURPOSE: Antimicrobials are a mayor part of hospital pharmacy budgets and must be considered in resource planning and spending projections . This study describes the profile of antibiotic use at a medium-sized hospital (by examining the ICU separately) and analyses its evolution over the period 1996-2000 . METHODS: Descriptive and retrospective study . Pharmacy records were reviewed to identify oral and parenteral antimicrobial agents administered to inpatients . Results were expressed in Daily Defined Doses (DDD) per 100 stays and day . RESULTS: During the five-year study period 176.162 DDD / 100 s-d of antibiotics were consumed in the ICU, whereas in the rest of the hospital usage was much lower (54.540 DDD / 100 s-d) . Aminoglycosides, cephalosporins, penicillins, glycopeptides and carbapenems were the most commonly used groups of antimicrobials in the ICU, and penicillins, cephalosporins, trimethoprim/sulfonamide combinations, aminoglycosides and quinolones in the rest of the hospital . CONCLUSIONS: ICUs have some special features which make them different to the rest of inpatient areas . Because of that fact we consider important to study this specific patient-care area separately. J Biol Chem, 2003 Jun 6, 278(23), 20851 - 9 Epub 2003 Feb 26. Targeting tuberculosis and malaria through inhibition of Enoyl reductase: compound activity and structural data; Kuo MR et al.; Tuberculosis and malaria together result in an estimated 5 million deaths annually . The spread of multidrug resistance in the most pathogenic causative agents, Mycobacterium tuberculosis and Plasmodium falciparum, underscores the need to identify active compounds with novel inhibitory properties . Although genetically unrelated, both organisms use a type II fatty-acid synthase system . Enoyl acyl carrier protein reductase (ENR), a key type II enzyme, has been repeatedly validated as an effective antimicrobial target . Using high throughput inhibitor screens with a combinatorial library, we have identified two novel classes of compounds with activity against the M . tuberculosis and P . falciparum enzyme (referred to as InhA and PfENR, respectively) . The crystal structure of InhA complexed with NAD+ and one of the inhibitors was determined to elucidate the mode of binding . Structural analysis of InhA with the broad spectrum antimicrobial triclosan revealed a unique stoichiometry where the enzyme contained either a single triclosan molecule, in a configuration typical of other bacterial ENR:triclosan structures, or harbored two triclosan molecules bound to the active site . Significantly, these compounds do not require activation and are effective against wild-type and drug-resistant strains of M . tuberculosis and P . falciparum . Moreover, they provide broader chemical diversity and elucidate key elements of inhibitor binding to InhA for subsequent chemical optimization. Antimicrob Agents Chemother, 2003 Mar, 47(3), 965 - 71 Modulation of the activity of secretory phospholipase A2 by antimicrobial peptides; Zhao H et al.; The antimicrobial peptides magainin 2, indolicidin, and temporins B and L were found to modulate the hydrolytic activity of secretory phospholipase A(2) (sPLA(2)) from bee venom and in human lacrimal fluid . More specifically, hydrolysis of phosphatidylcholine (PC) liposomes by bee venom sPLA(2) at 10 micro M Ca(2+) was attenuated by these peptides while augmented product formation was observed in the presence of 5 mM Ca(2+) . The activity of sPLA(2) towards anionic liposomes was significantly enhanced by the antimicrobial peptides at low {Ca(2+)} and was further enhanced in the presence of 5 mM Ca(2+) . Similarly, with 5 mM Ca(2+) the hydrolysis of anionic liposomes was enhanced significantly by human lacrimal fluid sPLA(2), while that of PC liposomes was attenuated . These results indicate that concerted action of antimicrobial peptides and sPLA(2) could improve the efficiency of the innate response to infections . Interestingly, inclusion of a cationic gemini surfactant in the vesicles showed an essentially similar pattern on sPLA(2) activity, suggesting that the modulation of the enzyme activity by the antimicrobial peptides may involve also charge properties of the substrate surface. Antimicrob Agents Chemother, 2003 Mar, 47(3), 941 - 7 Alteration of Escherichia coli topoisomerase IV to novobiocin resistance; Hardy CD et al.; DNA gyrase and topoisomerase IV (topo IV) are the two essential type II topoisomerases of Escherichia coli . Gyrase is responsible for maintaining negative supercoiling of the bacterial chromosome, whereas topo IV's primary role is in disentangling daughter chromosomes following DNA replication . Coumarins, such as novobiocin, are wide-spectrum antimicrobial agents that primarily interfere with DNA gyrase . In this work we designed an alteration in the ParE subunit of topo IV at a site homologous to that which confers coumarin resistance in gyrase . This parE mutation renders the encoded topo IV approximately 40-fold resistant to inhibition by novobiocin in vitro and imparts a similar resistance to inhibition of topo IV-mediated relaxation of supercoiled DNA in vivo . We conclude that topo IV is a secondary target of novobiocin and that it is very likely to be inhibited by the same mechanism as DNA gyrase. Antimicrob Agents Chemother, 2003 Mar, 47(3), 932 - 40 In vivo killing of Porphyromonas gingivalis by toluidine blue-mediated photosensitization in an animal model; Komerik N et al.; Porphyromonas gingivalis is one of the major causative organisms of periodontitis and has been shown to be susceptible to toluidine blue-mediated photosensitization in vitro . The aims of the present study were to determine whether this technique could be used to kill the organism in the oral cavities of rats and whether this would result in a reduction in the alveolar bone loss characteristic of periodontitis . The maxillary molars of rats were inoculated with P . gingivalis and exposed to up to 48 J of 630-nm laser light in the presence of toluidine blue . The number of surviving bacteria was then determined, and the periodontal structures were examined for evidence of any damage . When toluidine blue was used together with laser light there was a significant reduction in the number of viable P . gingivalis organisms . No viable bacteria could be detected when 1 mg of toluidine blue per ml was used in conjunction with all light doses used . On histological examination, no adverse effect of photosensitization on the adjacent tissues was observed . In a further group of animals, after time was allowed for the disease to develop in controls, the rats were killed and the level of maxillary molar alveolar bone was assessed . The bone loss in the animals treated with light and toluidine blue was found to be significantly less than that in the control groups . The results of this study show that toluidine blue-mediated lethal photosensitization of P . gingivalis is possible in vivo and that this results in decreased bone loss . These findings suggest that photodynamic therapy may be useful as an alternative approach for the antimicrobial treatment of periodontitis. Eur J Biochem, 2003 Mar, 270(5), 911 - 20 Distinguishing between different pathways of bilayer disruption by the related antimicrobial peptides cecropin B, B1 and B3; Chen HM et al.; Different pathways of bilayer disruption by the structurally related antimicrobial peptides cecropin B, B1 and B3, revealed by surface plasma resonance analysis of immobilized liposomes, differential scanning calorimetry of peptide-large unilamellar vesicle interactions, and light microscopic analysis of peptide-treated giant unilamellar vesicles, have been identified in this study . Natural cecropin B (CB) has one amphipathic and one hydrophobic alpha-helix, whereas cecropins B1 (CB1) and B3 (CB3), which are custom-designed, chimaeric analogues of CB, possess either two amphipathic or two hydrophobic alpha-helices, respectively . Surface plasma resonance analysis of unilamellar vesicles immobilized through a biotin-avidin interaction showed that both CB and CB1 bind to the lipid bilayers at high concentration (>10 microm); in contrast, CB3 induces disintegration of the vesicles at all concentrations tested . Differential scanning calorimetry showed the concentration-dependent effect of bilayer disruption, based on the different thermotrophic phase behaviours and the shapes of the thermal phase-transition curves obtained . The kinetics of the lysis of giant unilamellar vesicles observed by microscopy demonstrated that both CB and CB1 effect a continuous process involving loss of integrity followed by coalescence and resolution into smaller vesicles, whereas CB3 induces rapid formation of irregular-shaped, nonlamellar structures which rapidly disintegrate into twisted, microtubule-containing debris before being completely destroyed . On the basis of these observations, models by which CB, CB1 and CB3 induce lysis of lipid bilayers are discussed. Eur Biophys J, 2002 Dec, 31(7), 554 - 8 Effects of membranotropic agents on mono- and multilayer structures of dipalmitoylphosphatidylcholine; Lisetski LN et al.; We have studied the action of some membranotropic agents (MTAs) on the parameters of mono- and multilayers of dipalmitoylphosphatidylcholine (DPPC) . The MTAs used included an antimicrobial drug, decamethoxinum, the model amphiphilic agent stearoyl-L-alpha-alanine, and cholesterol as a reference substance . Using differential scanning calorimetry and the Langmuir monolayer technique, we measured the temperature and enthalpy of the main phase transition of DPPC, the mean molecular area, the collapse pressure and the free energy of the mixed monolayers of DPPC and MTA . A good correlation has been obtained between the structure of the MTA used and changes in the parameters of both mono- and multilayers . Thus, for cholesterol, its well-known condensing effect in the L alpha phase correlates with its behavior in the mixed monolayers . The disturbing action of decamethoxinum (depression of the phase transition in DPPC multilayers and relatively high free energy of mixing in monolayers) is presumably connected with interaction of its charged ammonium moieties with polar phospholipid heads . At the same time, stearoyl-L-alpha- alpha-alanine condensed the lipid layers and increased the melting point of DPPC, owing to its interaction with both polar and non-polar lipid moieties . One can conclude that the three MTAs used can really be considered as representative examples of three different types of behavior in mono- and multilayers. Biopolymers, 2003 Mar, 68(3), 407 - 21 Application of the empirical force field to macrocyclic ion carriers, siderophores, and biomimetic analogs; Felder CE et al.; The empirical force field (EFF), developed by Prof . Lifson, was applied to the study of macrocyclic alkali ion carriers and to di- and tripodal and open chain siderophores and synthetic biomimetic molecules binding transition metals . The highly symmetric nature of these structures facilitated a favorable coordination geometry of the ligating groups about the metal, which helped organize the entire molecule into a fairly rigid structure . In our combined experimental-theoretical approach, EFF calculations were used to help predict likely candidates to synthesize, and provided a wealth of structural data to complement what we learned from the spectroscopic measurements, while feedback from these measurements allowed us to continue improving the EFF itself . The simple, highly modular design of the biomimetic analogs allowed rapid synthesis and systematic examination of a large number of related structures, as well as facilitating an efficient, piecewise conformational scanning for the theoretical calculations . In the early years, we focused on macrocyclic polylactones and lactams binding monovalent alkali ions, particularly the natural products enniatin and valinomycin, including inside a crystal lattice . Later we switched to bi- and tridentate siderophores, natural microbial iron carriers, and synthetic biomimetic analogs-in particular, of enterobactin, ferrichrome, and ferrioxamine B . Over the years a large number of biomimetic siderophores have been prepared, some active in a broad range of microorganisms while others are highly species specific . The results of this work have broad applications in many areas, including the design of novel drugs and antimicrobial agents, helical polymeric structures, and polynuclear metal complexes . J Biomed Mater Res A, 2003 Mar 15, 64(4), 591 - 9 Fibroblast growth on surface-modified dental implants: an in vitro study; Groessner-Schreiber B et al.; A major consideration in designing dental implants is the creation of a surface that provides strong attachment between the implant and bone, connective tissue, or epithelium . In addition, it is important to inhibit the adherence of oral bacteria on titanium surfaces exposed to the oral cavity to maintain plaque-free implants . Previous in vitro studies have shown that titanium implant surfaces coated with titanium nitride (TiN) reduced bacterial colonization compared to other clinically used implant surfaces . The aim of the present study was to examine the support of fibroblast growth by a TiN surface that has antimicrobial characteristics . Mouse fibroblasts were cultured on smooth titanium discs that were either magnetron-sputtered with a thin layer of titanium nitride, thermal oxidized, or modified with laser radiation (using a Nd-YAG laser) . The resulting surface topography was examined by scanning electron microscopy (SEM), and surface roughness was estimated using a two-dimensional contact stylus profilometer . A protein assay (BCA assay) and a colorimetric assay to examine fibroblast metabolism (MTT) were used . Cellular morphology and cell spreading were analyzed using SEM and fluorescence microscopy . Fibroblasts on oxidized titanium surfaces showed a more spherical shape, whereas cells on laser-treated titanium and on TiN appeared intimately adherent to the surface . The MTT activity and total protein were significantly increased in fibroblasts cultured on titanium surfaces coated with TiN compared to all other surface modifications tested . This study suggests that a titanium nitride coating might be suitable to support tissue growth on implant surfaces . Phytother Res, 2003 Feb, 17(2), 168 - 73 Cytotoxic sesquiterpene lactones from Centaurothamnus maximus and Vicoa pentanema; Muhammad I et al.; The aerial parts of Centaurothamnus maximus yielded three cytotoxic guaianolides, chlorojanerin (1), cynaropicrin (2) and janerin (3) . The structure elucidation of 1-3 was based on (1)H and (13)C NMR data, mainly 2D-NMR (1)H-(1)H COSY and (1)H-(13)C HETCOR experiments . Compounds 1-3 showed in vitro cytotoxic activity against human cancer cell lines of malignant melanoma (SK-MEL), epidermoid (KB), ductal (BT-549) and ovarian (SK-OV-3) carcinomas with IC(50) values of 2-6 microgram/mL . In addition, 12 sesquiterpene lactones (4-15), isolated previously from the aerial parts of Vicoa pentanema, were evaluated for cytotoxic and antimicrobial activities . 2alpha- Acetoxy-3beta-hydroxyalantolactone (10) and 8beta-hydroxyparthenolide (14) were found to be the main cytotoxic agents (IC(50) values of 2-6 microgram/mL against SK-MEL, BT-549 and SK-OV-3), while lactones 4, 5, 11 and 15 selectively inhibited the growth of human malignant melanoma (IC(50) value of 3.6-7.3 microgram/mL) . Cell aggregation and cell adhesion assays, using HL-60 and HeLa cell lines, evaluated the effect of cytotoxic constituents 1-3, 10 and 14 on immune response and inflammation . Phytother Res, 2003 Feb, 17(2), 152 - 4 Composition and antimicrobial activity of the essential oil of Hypericum rumeliacum subsp . apollinis (Boiss . & Heldr.); Couladis M et al.; The composition and the antimicrobial activity of the aerial parts of Hypericum rumeliacum are reported . Analysis was carried out by GC/MS . The major constituents were alpha-pinene (43.80%), beta-pinene (9.82%), dehydro-aromadendrene (6.81%) and alpha-copaene (5.41%) . The essential oil showed a moderate in vitro activity against the six Gram negative and positive bacteria and a stronger one against the three-tested pathogenic activity . Ann Hematol, 2003 Feb, 82(2), 98 - 103 Epub 2003 Feb 05. Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients? Schuttrumpf S, Binder L, Hagemann T, Berkovic D, Trumper L, Binder C. Plasma concentrations of procalcitonin (PCT) have been shown to be elevated in bacterial and fungal infections . In contrast to C-reactive protein (CRP), PCT is not elevated in inflammations of noninfectious origin . Febrile inflammatory conditions are frequent in patients with hemato-oncological diseases . A reliable marker to discriminate infectious inflammations from drug-related and tumor-associated fever is still lacking . To evaluate the impact of PCT in this setting, PCT and CRP were prospectively measured in 95 febrile hemato-oncological patients . Infections could be identified in 40 of 95 patients: 38 of 95 had fever of unknown origin (FUO), 9 patients were suspected to suffer from drug-related fever, and 8 patients from tumor-associated fever . In the noninfection group (drug-related and tumor-associated fever), PCT levels were significantly lower than in patients with infections (P<0.001) or FUO (P<0.001) . Differences were still highly significant comparing patients with suspected drug-related or tumor-associated fever alone with the infection or the FUO cohort . All eight patients with tumor-associated fever as well as eight of the nine patients with drug-related fever had PCT levels within the normal range (<0.5 micro g/l) . CRP values only partially allowed discrimination between the various subgroups . Differences were significant between patients with drug-related fever and the infection (P=0.001) or FUO group (P=0.004) . However, as CRP levels were far above the normal range also in the patients with drug-related fever, the significance of individual values was rather limited . In conclusion, PCT may provide useful additional information to assess the clinical significance of febrile conditions . PCT may facilitate the decision on when to initiate antimicrobial or cytotoxic therapy. Am J Respir Cell Mol Biol, 2003 Jun, 28(6), 738 - 45 Epub 2002 Dec 30. The antimicrobial activity of the cathelicidin LL37 is inhibited by F-actin bundles and restored by gelsolin; Weiner DJ et al.; Antimicrobial peptides are part of the innate host defense system, and inactivation of these peptides is implicated in airway infections in cystic fibrosis (CF) . The sputum of patients with CF contains anionic polyelectrolytes, including F-actin and DNA not found in normal airway fluid . These anionic filaments aggregate to contribute to the altered viscoelastic properties of CF sputum . We hypothesized that the airway components stabilizing bundles of F-actin and DNA are in part cationic antimicrobial agents, and that appropriate modification of diseased airway fluid of patients with CF might dissociate these bundles and restore antimicrobial activity . We demonstrate that the human cathelicidin peptide LL37 forms bundles with F-actin and DNA, which are dissolved by gelsolin and DNase, respectively . Coincident with bundle formation, antimicrobial activity of LL37 is inhibited by F-actin and DNA . Pseudomonas bacteria were killed by low concentrations of LL37, but killing was significantly reduced in the presence of F-actin . The actin filament-fragmenting protein gelsolin restored bactericidal activity nearly completely . In a growth inhibition assay, the effects of F-actin were confirmed, and DNA was also shown to inhibit the activity of LL37 . When added to CF sputum, gelsolin significantly reduced the growth of bacteria, suggesting activation of endogenous antimicrobial factors . These findings may have therapeutic implications for treatments previously thought to alter only the viscoelastic properties of airway secretions and amplify the possible advantage of gelsolin in CF treatment. Am J Respir Cell Mol Biol, 2003 Jul, 29(1), 71 - 80 Epub 2003 Jan 23. ORFeome-based search of airway epithelial cell-specific novel human {beta}-defensin genes; Kao CY et al.; beta-Defensin is one of the major host defense shields produced by various tissues and organs against microbial infection . To date, four human beta-defensins (DEFBs) gene products that share a consensus six-cysteine motif have been discovered . The hidden Markov model (HMM) profile was constructed from the common features of those known beta-defensin peptides to search for additional novel DEFB genes . A genome-wide search of the profile against ORFeome-based peptide databases (e.g., Ensembl project) led to the identification of six new DEFB members that also shared the conserved six-cysteine motif . Phylogenetic analysis supported a close relationship of these six new members with existing DEFB genes . Polymerase Chain Reaction studies of human tissue cDNA panels confirmed the expression of all six novel DEFB genes in various tissues . Two of them, DEFB106 and DEFB109, were expressed in the lung . A pilot study with cRNA probes for in situ hybridization and a synthetic propeptide for the functional characterization demonstrated the tissue-/cell-specific expression and the strong antimicrobial activity of DEFB106 . These results support the utility of ORFeome-based HMM search in gene discovery for members of a specific gene family . The novel DEFB genes identified in this study may significantly contribute to overall antimicrobial host defenses. Jpn J Antibiot, 2002 Sep, 55 Suppl A, 111 - 8 {Antimicrobial susceptibility and beta-lactamase productivity of recent clinical isolates during the period between December 1999 and February 2000}; Notake S et al.; Antimicrobial susceptibility testings of 24 antimicrobial agents against 605 clinical strains belonging to 10 species were carried out according to the micro-broth dilution method of NCCLS M7-A4 . The productivity of beta-lactamase was also determined against them isolated at 8 medical facilities in Nagano prefecture, Japan during the period between December 1999 and February 2000 . When applied the nitrocefin method, beta-lactamase productivity was demonstrated to be positive for 89.2% of 74 S . aureus, 4.3% of 94 H . influenzae, and 100% of 69 M . (B.) catarrhalis isolates . On the other hand, when used the acidometry method, penicillinase/cephalosporinase were found to be positive for 21.2%/9.6% of 52 E . coli, 29.0%/3.2% of 31 K . pneumoniae, 53.2%/100% of 47 E . cloacae, 0%/11.1% of 99 S . marcescens, and 25.9%/55.6% of 54 P . aeruginosa isolates, respectively . Among the beta-lactamase-producers including P . aeruginosa isolates, only 2 E . coli isolates were found to be ESBL-producers . Besides, 9.6% (9/94) of H . influenzae isolates were proved to be BLNAR strains. Hua Xi Yi Ke Da Xue Xue Bao, 2002 Jan, 33(1), 87 - 90 {Isolation and purification of antibacterial polypeptides from human LAK cells}; Zhang Q et al.; OBJECTIVE: To isolate and purify new antibiotic peptides from human lymphokine activated killer (LAK) cells . METHODS: Preparative Acid-Urea Polyacrylamide Gel Electrophoresis and Reverse Phase HPLC were performed to isolate and purify polypeptides from the acid extract of human LAK cells . The molecule weight was analyzed by Tricine-SDS-PAGE . Radial agar diffusion assay was used to analyze the antibacterial activities . RESULTS: Several antibiotic peptides were isolated . Two peptides were purified from fractions HLP-2, HLP-3, which had molecular weight of around 7.9 x 10(3) u and 4 x 10(3) u and were named HLP-2b and HLP-3a, respectively . Four peptides with molecular weight of 7.2 x 10(3) u, 10.4 x 10(3) u, 6.2 x 10(3) u and 6.2 x 10(3) u were almost purified and were named HLP-2a, HLP-2c, HLP-3b and HLP-3c, respectively . HLP-2b, HLP-2a, HLP-2c, HLP-3b and HLP-3c all had antimicrobial activities against S . Aureus and C . Albicans, and HLP-3a against S . Aureus only . CONCLUSION: Human LAK cells contained a variety of antimicrobial peptides. Trends Microbiol, 2003 Feb, 11(2), 80 - 6 The basis of persistent bacterial infections; Rhen M et al.; Selected bacterial pathogens, such as Helicobacter pylori and Mycobacterium tuberculosis, establish persistent infections in mammalian hosts despite activating inflammatory and antimicrobial responses . The strategies used to overcome host defense responses vary with the anatomical location of the infection but often rely on deliberate manipulations of the host cell responses . Phylogenetically unrelated bacteria can share similar strategies for the establishment of persistence and, in selected examples, one even can define homologous "persistence" genes . Such observations suggest that persistent infection is a specific phase in infection pathogenesis rather than a fortuitous imbalance in the host-pathogen interaction. Chem Phys Lipids, 2003 Jan, 122(1-2), 107 - 20 Interaction of antimicrobial peptides from Australian amphibians with lipid membranes; Marcotte I et al.; Solid-state NMR and CD spectroscopy were used to study the effect of antimicrobial peptides (aurein 1.2, citropin 1.1, maculatin 1.1 and caerin 1.1) from Australian tree frogs on phospholipid membranes . 31P NMR results revealed some effect on the phospholipid headgroups when the peptides interact with DMPC/DHPC (dimyristoylphosphatidylcholine/dihexanoylphosphatidylcholine) bicelles and aligned DMPC multilayers . 2H NMR showed a small effect of the peptides on the acyl chains of DMPC in bicelles or aligned multilayers, suggesting interaction with the membrane surface for the shorter peptides and partial insertion for the longer peptides . 15N NMR of selectively labelled peptides in aligned membranes and oriented CD spectra indicated an alpha-helical conformation with helix long axis approximately 50 degrees to the bilayer surface at high peptide concentrations . The peptides did not appear to insert deeply into PC membranes, which may explain why these positively charged peptides preferentially lyse bacterial rather than eucaryotic cells. Urology . 2003 Feb;61(2):462. Osteomyelitis of the pubis: a complication of a chronic indwelling catheter; Stern JA et al.; Pubic osteomyelitis typically occurs after pelvic surgery or trauma . We present a case of pubic osteomyelitis ensuing from a chronic indwelling (for 8 years) urethral catheter in a 40-year-old woman . She presented initially with fever of unknown origin, and broad-spectrum antimicrobial therapy was initiated . Computed tomography of the abdomen and pelvis ultimately revealed cortical destruction of the pubic symphysis, and open biopsy confirmed osteomyelitis . Osteomyelitis of the pubis is a rare entity that typically results from bacteremia, trauma, or the spread of an adjacent focus of infection from previous pelvic surgery . To our knowledge, this is the first report of pubic osteomyelitis resulting from a chronic indwelling urethral catheter. Crit Care Nurs Clin North Am, 2003 Mar, 15(1), 79 - 87 The role of early enteral nutrition in protecting premature infants from sepsis; Strodtbeck F; Care of critically ill, preterm infants is a major challenge . Because of their small size and complex health problems, preterm infants require long-term hospitalization in the intensive care unit where they are exposed to serious microorganisms and other antigens that can overwhelm their immature immune systems . As smaller and more fragile preterm infants are surviving NICU care, these infants are at increased risk for nosocomial infections . Although modern antimicrobial agents are invaluable in the management of infection, they can result in biologic stress to the immature physiology of the preterm infant . Nonpharmacologic strategies to enhance the immunocompetence of the preterm immune systems provide another alternative in the management of these infants . Because the gastrointestinal tract is one of the largest immune organs within the body, strategies to maximize its immune functions can improve the outcome of these infants and help prevent or minimize the risk of infection . One such strategy is the early introduction of enteral feedings designed to stimulate or prime the gut . Early introduction of enteral feedings in the acutely ill preterm infant appears to be well tolerated in a variety of small clinical studies . Although the studies vary considerably in design and variables measured, collectively they show a solid trend toward improved outcomes . By preventing the negative consequences of a prolonged period of NPO, early enteral feedings promote the normal processes of the gut as a physical, mechanical, physiologic, and immunologic barrier . A solid understanding of the pathophysiology of prolonged NPO status and the physiology of the gut's immune properties enables critical care nurses to improve care of these vulnerable NICU patients. Surg Infect (Larchmt), 2000, 1(1), 31 - 8 Diagnosis and treatment of intra-abdominal abscesses; Sirinek KR; Despite recent advances in the diagnosis and management of intra-abdominal abscesses, these infections still cause substantial morbidity and mortality . Low pH, large bacterial inocula, poor perfusion, the presence of hemoglobin, and large amounts of fibrin (which impedes antibiotic penetration) make the abscess a cloistered environment that is penetrated poorly by many antimicrobial therapies . Therefore, management of these infections requires prompt recognition, early localization, and effective drainage, as well as appropriate antimicrobial use . Although various imaging techniques, such as ultrasonography, gallium scans, and indium-labeled white-blood-cell scans, can be used for the diagnosis and localization of intra-abdominal abscesses, computer-assisted tomography is the most useful study . Once the diagnosis is made and the abscess is localized, treatment should begin promptly . Percutaneous or open surgical drainage should be used . Broad-spectrum antibiotics should be given until culture and sensitivity data are obtained . Once these data are obtained, a therapy with appropriate coverage that is likely to work in the abscess environment should be chosen . Percutaneous drainage is inappropriate for abscesses in the posterior subphrenic space or in the porta hepatis, for those among loops of small bowel, for suspected echinococcal cysts, and for abscesses containing necrotic or neoplastic tissues . Finally, surgeons need to be cognizant of risk factors, such as advanced age, obesity, complex abscesses, and high Acute Physiology and Chronic Health Evaluation (APACHE) II or APACHE III scores, which correlate with poor outcomes for these patients. Surg Infect (Larchmt), 2000 Summer, 1(2), 115 - 23; discussion 125-6 Surgeons and infectious disease specialists: different attitudes towards antibiotic treatment and prophylaxis in common abdominal surgical infections; Gorecki PJ et al.; BACKGROUND: The role of medical infectious disease (ID) specialists in the treatment of surgical infections is increasing but no information is available regarding the therapeutic perception held by these non-surgeons treating surgical infections . The purpose of this study was to assess the attitude of the ID specialists towards antibiotic treatment and prophylaxis of common abdominal surgical infections and to compare it with that of surgeons "interested" in this field . METHODS: A questionnaire, polling opinions regarding the management of common surgical infections, was sent to 396 medical ID specialists (New York State) and 515 surgeon members of the Surgical Infection Society (SIS) . The questions covered areas involving choice of antibiotics, and timing and duration of treatment in given clinical scenarios, including elective and emergent colorectal surgery, perforated peptic ulcer, and appendicitis . RESULTS: Response rates for the medical and surgical groups were 10.1% and 15.6%, respectively . Regarding prophylactic use of antimicrobials, the pattern of administration was similar for the two groups . Regarding therapeutic use, on average medical ID specialists used antibiotics twice as long as the surgical group . The main reason identified was the failure of medical ID specialists to understand the conceptual difference between contamination and infection . CONCLUSIONS: Medical ID specialists may overtreat common surgical infections with antibiotics . Surgical infections should be treated by surgeons. Surg Infect (Larchmt), 2001 Summer, 2(2), 145 - 50; discussion 150-2 Necrotizing soft tissue infections: are we making any progress? Malangoni MA. BACKGROUND: Necrotizing soft tissue infections are a group of diseases with significant associated mortality . A wide spectrum of bacteria can be involved, and diagnosis can be difficult . METHODS: Review of pertinent literature of the diagnosis and therapy of necrotizing soft-tissue infection . RESULTS: Mortality and other adverse outcomes are directly related to advanced age, the presence of organ system failure, lactic acidemia, the percentage of body surface area involved with infection, and delays in operative management . Patients usually die early from the consequences of septic shock, whereas late mortality is related to multiple organ failure . CONCLUSION: Early recognition and treatment can lower mortality from necrotizing soft tissue infection . Prompt operative debridement, broad-spectrum antimicrobials, and physiologic support are important components of treatment. Surg Infect (Larchmt), 2001, 2 Suppl 1, S23 - 32 The role of beta-lactam/beta-lactamase inhibitor combinations in surgical infections; Sayek I; Many surgical infections are characterized by synergistic polymicrobial mixed infection, for which broad-spectrum antimicrobial therapy is usually administered on an empiric basis . Until relatively recently, standard empiric therapeutic regimens have involved the use of two or more antibiotics, such as aminoglycosides and anti-anaerobic agents, to achieve adequate aerobic and anaerobic coverage . There are often substantial drawbacks, however, such as drug-induced toxicity and high costs of treatment . Evidence from a number of clinical studies suggests that single-agent therapy with beta-lactam/beta-lactamase inhibitor combinations is a suitable and cost-effective alternative to multidrug regimens, as well as to monotherapy with cephalosporins or carbapenems in the treatment of intra-abdominal, gynecologic, and diabetic foot infections, and brain abscesses . These agents are also suitable for use in perioperative prophylaxis and may offer benefits over other agents in terms of reduced incidence of surgical wound infections and lower costs. FASEB J, 2003 Apr, 17(6), 776 - 8 Epub 2003 Feb 19. The N- and C-terminal fragments of ubiquitin are important for the antimicrobial activities; Kieffer AE et al.; Secretory granules of chromaffin cells contain catecholamines and several antimicrobial peptides derived from chromogranins and proenkephalin-A . These peptides are secreted in the extracellular medium following exocytosis . Here, we show that ubiquitin is stored in secretory chromaffin granules and released into the circulation upon stimulation of chromaffin cells . We also show that the C-terminal fragment (residues 65-76) of ubiquitin displays, at the micromolar range, a lytic antifungal activity . Using confocal laser scan microscopy and rhodamine-labeled synthetic peptides, we could demonstrate that the C-terminal peptide (residues 65-76) is able to cross the cell wall and the plasma membrane of fungi and to accumulate in fungi, whereas the N-terminal peptide (residues 1-34) is stopped at the fungal wall level . Furthermore, these two peptides act synergistically to kill filamentous fungi . Because of the interaction of the C-terminal sequence of ubiquitin with calmodulin, the synthetic peptide (residues 65-76) was tested in vitro against calmodulin-dependent calcineurin, an enzyme crucial for fungal growth . This peptide was found to inhibit the phosphatase activity of calcineurin . Our data show a new property of ubiquitin C-terminal-derived peptide (65-76) that could be used with N-terminal peptide (1-34) as a new potent antifungal agent. Int J Food Microbiol, 2003 May 15, 82(3), 273 - 9 Isolation of Escherichia coli O157:H7 from foods in Greece; Dontorou C et al.; The presence of Escherichia coli O157:H7 in various foods of animal origin was surveyed in northwestern Greece . Six hundred samples of unpasteurized cows', ewes' and goats' milk, raw minced meat, uncooked frozen beef hamburgers, sandwiches (containing ham or turkey, mixed vegetable salad with mayonnaise and lettuce), fresh traditional Greek pork sausages and swine intestines appropriate for traditional Greek kokoretsi were assayed for E . coli serogroup O157:H7 using the standard cultural method and the immunomagnetic separation technique . The pathogen was detected in 1 out of 100 (1.0%) samples of ewes' milk, 1 out of 75 (1.3%) fresh sausages and 1 out of 50 (2.0%) swine intestines prepared for kokoretsi . The isolated strains were nonsorbitol fermenters, MUG-negative, O157 agglutinating, verotoxin-producing and carried both VT1 and VT2 genes . The three isolated strains were tested for antibiotic resistance and were found to be susceptible to eight antimicrobial agents (ampicillin, chloramphenicol, kanamycin, nalidixic acid, norfloxacin, streptomycin, sulfamethoxazole-trimethoprim and tetracycline). Eur J Med Chem, 2003 Jan, 38(1), 89 - 100 Synthesis and preliminary evaluation of some N-{5-(2-furanyl)-2-methyl-4-oxo-4H-thieno{2,3-d}pyrimidin-3-yl}-carboxamide and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno{2,3-d}pyrimidin-4-ones as antimicrobial agents; Chambhare RV et al.; Two series of N-{5-(2-furanyl)-2-methyl-4-oxo-4H-thieno{2,3-d}pyrimidin-3-yl}-carboxamide (4a-m) and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno{2,3-d}pyrimidin-4-ones (5a-m) were synthesised using appropriate synthetic route . All the test compounds 4a-m and 5a-m were assayed in vitro for antibacterial activity against two different strains of Gram-negative (Escherichia coli and S . typhi) and Gram-positive (S . aureus, B . subtilis) bacteria and the antimycobacterial activity was evaluated against M . tuberculosis and M . avium strains . The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards . The test compounds have shown significant antibacterial and antimycobacterial activity against all the microbial strains used, when tested in vitro . In general, along with the thienopyrimidinone ring, substituted amido or imino side chain at position 3 is essential for antimicrobial activity . Among the compounds tested, compounds 4c, 4e and 4g in N-{5-(2-furanyl)-2-methyl-4-oxo-4H-thieno{2,3-d}pyrimidin-3-yl}-carboxamide series and compounds 5c, 5e and 5g in 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno{2,3-d}pyrimidin-4-ones series were found to be the most potent . Further the toxicity of most potent compounds 4c, 4e and 4g and 5c, 5e and 5g were assessed using hemolytic assay and minimal hemolytic concentration (MHCs) were determined . In general, test compounds were found to be non-toxic up to a dose level of 200 micromol L(-1) (MHC) . World Health Organ Tech Rep Ser, 2002, 911, i - vi, 1-66, back cover Evaluation of certain veterinary drug residues in food; Joint FAO/WHO Expert Committee on Food Additives; This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food . The first part of the report considers risk assessment principles and presents the views of the Committee on the FAO/WHO Project to update principles and methods for the risk assessment of chemicals in food . Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three anthelminthic agents (doramectin, ivermectin and tiabendazole), seven antimicrobial agents (cefuroxime, dihydrostreptomycin and streptomycin, lincomycin, neomycin, oxytetracycline and thiamphenicol), four insecticides (cyhalothrin, cypermethrin and alpha-cypermethrin, and phoxim) and one production aid (melengestrol acetate) . Annexed to the report is a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and Maximum Residue Limits and further information required. Lijec Vjesn, 2002 Sep, 124 Suppl 1, 72 - 8 {Helicobacter pylori--overview of therapy}; Katicic M et al.; The clinical significance of Helicobacter pylori infection in the etiopathogenesis of many gastroduodenal disorders, especially peptic ulcer disease and current awareness of the benefits of its eradication has entirely changed the current treatment of these diseases . Eradication was already defined as the disappearance of Helicobacter pylori from the gastric mucosa (finding negativization) confirmed at least 4 weeks (or later) after completed antibiotic eradication therapy . The regimen has to be simple, cheap and tolerable so that the patient could carry it out completely and as easy as possible (good compliance is required) . The success of Helicobacter pylori eradication, evaluated by the strict "intention-to-treat" criteria, has to be higher than 80% . Current modern therapy should be triple and not longer than 7 days . One of three proton pump inhibitors is recommended as the antisecretory component (omeprazole, pantoprazole or lansoprazole) . Two of three following antibiotis is added to this therapy: metronidazole/tinidazole, clarithromycin or amoxicillin . Treatment failure and growing number of antimicrobial resistant Helicobacter pylori strains require new ways of therapy and more effective drugs . Our results of 7-, 10- and 14-day therapy consisting of omeprazole, amoxicillin and metronidazole are poorer than those of drug combination including clarithromycin instead of amoxicillin . The results of Clinical Hospital "Merkur" showed that combination of amoxicillin, metronidazole and pantoprazole was more effective than the same combination with omeprazole, and the opposite was true for metronidazole and azithromycin combined with omeprazole and pantoprazole, respectively . The results of other medical centers prescribing the same eradication protocols were completely different . The differences are probably caused by poor patient compliance. J Allergy Clin Immunol, 2003 Feb, 111(2 Suppl), S548 - 59 10 . Drug allergy; Gruchalla RS; Adverse drug reactions are common, but only 6% to 10% are immunologically mediated . Unlike most adverse drug reactions, allergic drug reactions are unpredictable . Whereas some drug-induced allergic reactions may be easily classified into one of the four Gell and Coombs hypersensitivity categories, many others that appear to have an immunologic component cannot be classified because of our lack of mechanistic information . Theoretically, any drug can induce an immune response . However, some drugs are more likely to elicit clinically relevant immune responses than are others . Drugs in this category include antimicrobial drugs, anticonvulsants, chemotherapeutic agents, heparin, insulin, protamine, and biologic response modifiers . After a drug-disease connection is established, it must be determined whether the reaction was immunologically mediated . Subsequently, confirmatory tests, if available, should be used to determine the allergic status of the patient . If these tests are not available, a graded challenge or desensitization may be considered, depending on the type of clinical reaction previously demonstrated and the need for drug readministration . Education of the patient and primary care physician is an important component of patient management. Protein Sci, 2003 Mar, 12(3), 438 - 46 Solution structure of termicin, an antimicrobial peptide from the termite Pseudacanthotermes spiniger; Da Silva P et al.; The solution structure of termicin from hemocytes of the termite Pseudacanthotermes spiniger was determined by proton two-dimensional nuclear magnetic resonance spectroscopy and molecular modeling techniques . Termicin is a cysteine-rich antifungal peptide also exhibiting a weak antibacterial activity . The global fold of termicin consists of an alpha-helical segment (Phe4-Gln14) and a two-stranded (Phe19-Asp25 and Gln28-Phe33) antiparallel beta-sheet forming a "cysteine stabilized alphabeta motif" (CSalphabeta) also found in antibacterial and antifungal defensins from insects and from plants . Interestingly, termicin shares more structural similarities with the antibacterial insect defensins and with MGD-1, a mussel defensin, than with the insect antifungal defensins such as drosomycin and heliomicin . These structural comparisons suggest that global fold alone does not explain the difference between antifungals and antibacterials . The antifungal properties of termicin may be related to its marked hydrophobicity and its amphipatic structure as compared to the antibacterial defensins . {SWISS-PROT accession number: Termicin (P82321); PDB accession number: 1MM0.} Dev Comp Immunol, 2003 Apr, 27(4), 305 - 11 A novel antimicrobial peptide from the sea hare Dolabella auricularia; Iijima R et al.; The sea hare Dolabella auricularia is a marine shell-less gastropod . Four cytotoxic glycoproteins named dolabellanin A, C, E and P were found in the animal previously . An antimicrobial factor was newly isolated from the sea hare's body-wall including skin and mucus . This factor is a novel peptide which consists of 33 amino acid residues, and is called dolabellanin B2 . Dolabellanin B2 was cytotoxically effective against some pathogenic microorganisms at a concentration of 2.5-100 microg/ml. Dev Comp Immunol, 2003 Apr, 27(4), 291 - 304 Amoebapores, archaic effector peptides of protozoan origin, are discharged into phagosomes and kill bacteria by permeabilizing their membranes; Andra J et al.; Antimicrobial peptides are widespread in animal species and their function as defensive molecules may even have appeared before the evolution of metazoa . The amoeboid protozoon Entamoeba histolytica discharge membrane-permeabilizing polypeptides named amoebapores into the phagosome in which engulfed bacteria are situated as evidenced here by confocal laser microscopy and electron microscopy using specific antibodies . We demonstrate that the purified three isoforms of the amoebic polypeptides exhibit complementary antibacterial activities in vitro . The potency of amoebapores were compared with that of antimicrobial peptides of phylogenetically widespread species by monitoring in parallel their activities against representatives of gram-positive and gram-negative bacteria and liposomes in various assays, and differences in the mechanism of membrane permeabilization became apparent . Northern blot analysis revealed that expression of genes coding for amoebapores and amoebic lysozymes is not dramatically changed upon co-culture of amoebae with bacteria indicating that the antimicrobial arsenal is rather constitutively expressed than induced in these primitive phagocytes. Dev Comp Immunol, 2003 Apr, 27(4), 283 - 9 Expression of penaeidin antimicrobial peptides in early larval stages of the shrimp Penaeus vannamei; Munoz M et al.; Penaeidins are a family of antimicrobial peptides constitutively produced and stored in the hemocytes of penaeid shrimps . We have determined the expression and the localization of penaeidins in the first early larval stages (Nauplius V, Zoea I, II, III and Mysis II) and in post-larvae (1 and 8) of the shrimp Penaeus vannamei . Using in situ hybridization and immunohistochemical analyses, we localized penaeidin transcripts and peptides in a few hemocytes of larvae from Mysis II stage . However, RT-PCR analyses showed that penaeidin mRNAs are already present in the early stage of Nauplius V . In addition, penaeidin expression could not be detected in other cells than hemocytes . Our observations highlight the potential involvement of penaeidins during larval development and the ontogeny of immune system through hemocytes during this period of life, where shrimps are particularly susceptible to infectious diseases. Int J Immunopathol Pharmacol, 2002 May, 15(2), 119 - 127 Serum procalcitonin, adenosine deaminase and its isoenzymes in the aetiological diagnosis of pneumonia in children; Hatzistilianou M et al.; A prospective study was undertaken to assess the usefulness of leukocyte count, serum C-reactive protein (CRP), procalcitonin (PCT), and the activities of total adenosine deaminase (tADA) and its isoenzymes ADA1 and ADA2, in the aetiological diagnosis of pneumonia in children . The study included three groups . Group A consisted of 23 children with bacterial pneumonia, group B of 50 children with viral and mycoplasmal pneumonia and group C of 46 healthy children . On the first day of admission in the clinic, blood samples were collected before the start of antimicrobial treatment, for culture, serological tests, leukocyte count and for the determination of CRP and PCT levels as well as tADA activity and its isoenzymes ADA1 and ADA2 . According to our results, the mean leukocyte count and the mean concentrations of PCT and CRP were significantly higher in the children of group A than those in groups B and C . The admission serum PCT concentration has a higher sensitivity, specificity and positive predictive value for bacterial pneumonia than either CRP or the leukocyte count . The mean serum tADA, ADA1 and ADA2 activity in children of group A was not significantly different from those in group C, while the difference between groups B and C was statistically significant . In conclusion, we found that CRP is a good marker for screening various infectious diseases, but it cannot be used to distinguish between bacterial and viral infections . Serum PCT measurement might be a useful tool for the physician for the aetiological diagnosis of pneumonia in children . Measurements of serum tADA and ADA2 activity may provide useful additional diagnostic information on the aetiology of pneumonia so that appropriate antibiotic therapy can be given promptly . Further studies with larger patients groups are required to confirm our results. J Agric Food Chem, 2003 Feb 26, 51(5), 1215 - 23 Homology similarity analysis of sequences of lactoferricin and its derivatives; Nakai S et al.; A new method, homology similarity analysis (HSA), was developed to investigate homology pattern similarities of selected segments within sequences of peptides . This new approach facilitated elucidation of the structure-function relationships of lactoferricin derivatives . Helix propensity of positions 4-9 in the lactoferricin sequence was the most important in determining the antimicrobial activity of lactoferricin against Escherichia coli, followed by cationic charge pattern at positions 4-9 and 1-3 . The pattern similarity of segments within sequences could be a useful tool for representing the distribution attributes of amino acid residue properties to the structure-function relationships of proteins and peptides, especially when used in conjunction with principal component similarity analysis followed by the regression version of artificial neural networks. Infection, 2003 Jan, 31(1), 3 - 8 A predictive model for the management of community-acquired pneumonia; Raz R et al.; BACKGROUND: Understanding what determines the prognosis of community-acquired pneumonia (CAP) is especially important for decisions on hospitalization and antimicrobial therapy . The objective of the present study was to compare the predictability of mortality in our patients to that of the pneumonia patient outcomes research team (PORT) study . PATIENTS AND METHODS: Data of 320 patients admitted with CAP were retrospectively evaluated and classified according to the published scheme . RESULTS: One-month mortality was 14.4%; 1-year mortality was 27.8%, two-thirds from new episodes . Univariate logistic regression risk factors for the 1-month mortality rate included leukocytosis, anemia, hypoalbuminemia, elevated blood urea nitrogen, >or= two comorbidities, tachycardia, tachypnea, acidosis, stupor, age > 65 years and high serum lactic dehydrogenase . These variables, except the last two, plus pleural effusion and bilateral infiltration were also risk factors for 1-year mortality . In the multivariate models, eight of these factors were significant risk factors, four for 1-month mortality and six for 1-year mortality . Our model for prediction of 1-month mortality had a sensitivity of 65%, specificity of 95% and accuracy of 91% . CONCLUSION: Agreement between predictions by our model and the published model was considerable, showing that most patients in the low score groups should not have been hospitalized. Auris Nasus Larynx, 2003 Feb, 30(1), 65 - 9 Effects of topical chlorhexidine applied to the rabbit nasal mucosa; Cankaya H et al.; OBJECTIVE: To search the effects of administration of various concentrations of a wide-spectrum antimicrobial agent, chlorhexidine, to the nasal mucosa . MATERIAL AND METHODS: About 0.20, 0.12, 0.06 and 0.03% concentrations of chlorhexidine gluconate were applied to the rabbit nasal mucosa as one puff twice a day throughout 5 days . Another group, treated with serum saline to the nose, behaved as the control group . On the fifth day following drug administration, specimens were taken from nasal mucosa of the rabbits and examined under light microscope . RESULTS: As a result of comparison between drug treated group and control group, with increasing drug concentrations progressively increased neutrophil infiltration in mucosa, ciliary loss in cells, and occasional metaplasia were observed . CONCLUSION: There is a linear, positive and strong association between concentrations of chlorhexidine and its irritative effects on rabbit nasal mucosa . While 0.20 and 0.12% concentrations of chlorhexidine cause excess irritation on the nasal cavity, 0.06 and 0.03% concentrations of chlorhexidine gluconate causes lower irritation and effects on the animals which have experimentally induced rhinosinusitis must be evaluated. Br J Dermatol, 2003 Feb, 148(2), 229 - 32 Antimicrobial photodynamic therapy: assessment of genotoxic effects on keratinocytes in vitro; Zeina B et al.; BACKGROUND: Work has shown that cutaneous microbial species associated with skin conditions of microbial aetiology are susceptible to killing by antimicrobial photodynamic therapy (APDT) using visible light and methylene blue . OBJECTIVES: To evaluate immediate and delayed genotoxicity of APDT on keratinocytes in vitro . METHODS: A combination of methylene blue (100 microg mL(-1)) and visible light (42 mW cm(-2)), as used in studies of microbe and keratinocyte cytotoxicity, was employed to test a human keratinocyte cell line (H103) for genotoxic damage by comet assay . RESULTS: The comet assay was able to detect genotoxic damage in H2O2-treated keratinocytes (positive control) . APDT did not cause either immediate or delayed genotoxic damage in keratinocytes following APDT of up to 180 min . CONCLUSIONS: APDT sufficient to reduce microbes by seven log cycles showed no detectable genotoxic effects on keratinocytes . APDT applied in vivo may represent a useful low-risk alternative to conventional antimicrobial treatment in dermatology. Acta Microbiol Pol, 2002, 51(3), 265 - 73 Antimicrobial activity of substituted 2-trifluoromethyl- and 2-pentafluoroethylbenzimidazoles; Wolinowska R et al.; Antibacterial and antifungal activity of 2-trifluoromethyl- and 2-pentafluoroethylbenzimidazoles, including a number of newly obtained derivatives, were examined by diffusion method (inhibition area diameter in solid agar medium) and minimum inhibitory concentration (MIC, in liquid and agar medium) . Some of the derivatives tested affected fungal colony morphology and exerted genotoxic effects in bacteria . Of the tested compounds, 5,6-dichlorosubstituted derivatives appeared the most active against the majority of microorganisms used. Acta Microbiol Pol, 2002, 51(3), 255 - 63 Primary resistance of Helicobacter pylori to antimicrobial agents in Polish children; Rozynek E et al.; Helicobacter pylori resistance to antimicrobial agents is an important factor compromising the efficacy of treatment . Therefore the aims of our study were: to determine the prevalence of H . pylori resistance to clarithromycin, metronidazole, amoxycillin and tetracycline in children prior to eradication therapy, to compare different methods of susceptibility testing and to detect mutations responsible for clarithromycin resistance . During 1996-2000, 259 H . pylori strains were isolated from antral gastric biopsies . Susceptibility to antimicrobials was determined by the agar dilution method and the Etest . Mutations in the 23S rRNA gene associated with clarithromycin resistance were analysed by PCR-RFLP and direct sequencing . Overall, ninety-six strains (37%) were resistant to metronidazole, 50 strains (19.3%) were resistant to clarithromycin, and 20 strains (7.7%) were simultaneously resistant to both drugs . All cultured isolates were sensitive to amoxycillin and only one isolate (0.4%) was resistant to tetracycline . The agar dilution method and the Etest showed a perfect category correlation for clarithromycin and 4% discrepancies for metronidazole . Primary resistance to clarithromycin was mainly associated with an A2143G mutation in the 23S rRNA gene of H . pylori . The study highlights the high prevalence of H . pylori primary resistance to clarithromycin in Polish children, which implies a need for pretreatment susceptibility testing. Pharmacotherapy, 2003 Feb, 23(2), 159 - 64 Risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin therapy; Carver PL et al.; STUDY OBJECTIVE: To evaluate risk factors for the development of arthralgias or myalgias associated with quinupristin-dalfopristin . DESIGN: Retrospective chart review and case-control analysis . SETTING: An 850-bed tertiary care medical center . PATIENTS: All adult and pediatric patients who had received quinupristin-dalfopristin through either a compassionate-use protocol (February 1996-October 1999) or in the year after quinupristin-dalfopristin was added to the hospital formulary (November 1999-October 2000) were included in this study . Case patients were those who developed arthralgias or myalgias while receiving quinupristin-dalfopristin therapy; control patients were those who received quinupristin-dalfopristin but did not develop arthralgias or myalgias . INTERVENTION: Medical records, pharmacy dispensing information, and microbiology data were reviewed by a physician and a pharmacist, both of whom specialized in infectious diseases . Presence or absence of arthralgias or myalgias was the primary outcome assessed . MEASUREMENTS AND MAIN RESULTS: Quinupristin-dalfopristin was administered to 68 patients during the period defined by the study . Arthralgias and myalgias could not be assessed in 18 of the 68 patients because they were sedated and paralyzed, or they were young children who could not communicate the presence of pain . Univariate analysis demonstrated that significant risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin were female sex, chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, major surgery, and receipt of either mycophenolate or cyclosporine . Multivariate analysis demonstrated a strong association with chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, and receipt of either cyclosporine or mycophenolate . Of 50 evaluable patients receiving quinupristin-dalfopristin, 25 had pain that may have been associated with this antimicrobial agent . CONCLUSION: The mechanism for development of arthralgias or myalgias associated with quinupristin-dalfopristin remains unknown, but these adverse events are more likely to occur in patients with chronic liver disease and those who have received a liver transplant or are receiving cyclosporine or mycophenolate. Lik Sprava, 2002, (7), 114 - 7 {Microbiological validation of the composition of "decaceol", an antiseptic prolonged-release drug}; Dykyi IL et al.; With the aid of different microbiological methods, antimicrobal properties of decametoxine, a home-produced antiseptic, were studied together with those of the synthetic zoelite NaA-base drug preparation . The antimicrobial activity of the above drug has been shown to be of a synergistic character that makes it a very promising medical agent which will, we believe, come to be widely used in medical practice. Rev Esp Quimioter, 2002 Dec, 15(4), 306 - 12 {The bacteriophages and their gene products as antimicrobial agents}; Garcia E et al.; The viruses that infect bacteria (bacteriophages or phages) were first isolated about 90 years ago . Phages have been fundamental tools in the development of molecular biology . Phages were early hypothesized as therapeutic agents for combatting pathogenic bacteria . However, the discovery and successful use of antibiotics to treat infectious diseases hindered this aim . the development of bacterial resistance to most available drugs has recently led researchers to test the possibilities of using phages as therapeutic agents . We review here recent achievements in this field, taking into consideration former bias in handling phages as well as previous achievements carried out in Eastern Europe where bacteriophages have been employed for decades as an alternative to antibiotics. J Hosp Infect, 2003 Feb, 53(2), 129 - 35 Pharmacokinetics of the antimicrobial agents rifampicin and miconazole released from a loaded central venous catheter; Rump AF et al.; The time course of rifampicin and miconazole concentrations after insertion of a polyurethane catheter loaded with these antibiotics were studied . Data from controlled release experiments in vitro were used, and the concentration time courses of the antimicrobials in serum were calculated by pharmacokinetic simulations . Systemic therapy using typical dosages (rifampicin 600 mg/day iv, miconazole 3 x 200 mg/day iv) results in rifampicin concentrations between 54 and 8424 microg/L, and miconazole concentrations between 3567 and 4676 microg/L . After insertion of a polyurethane catheter loaded with these antibiotics, the maximal concentrations after catheter placement were determined as 6 microg/L at 10.7h for rifampicin, and 13 microg/L at 28.6 h for miconazole . Assuming that the total amount of antibiotics incorporated in the catheter matrix were bioavailable ('worst case'), the resulting maximal concentrations calculated by simulation are 10 microg/L for rifampicin and 65 microg/L for miconazole . Maximal concentrations of rifampicin or miconazole resulting from the insertion of a polyurethane catheter loaded with these antibiotics are, therefore, far below the concentrations resulting from a systemic therapy with the same antimicrobial agents . Even in the worst case, the danger of selecting resistant bacterial strains seems remote because the systemic drug levels are magnitudes of order below subinhibitory concentrations . J Hosp Infect, 2003 Feb, 53(2), 91 - 6; quiz 149 Principles of good use of antibiotics in hospitals; Guven GS et al.; Rational use of antimicrobials is a key element for a successful strategy against development of resistance to antimicrobials . The physician should establish the need and the reason for therapy, select the appropriate antimicrobial agent, and then decide on the optimum dose and dosing interval, duration, as well as route of administration . In a particular hospital, the present status of antimicrobial use should be determined, and a strategy should be developed to improve it . This usually encompasses a combination of educative, facilitative and restrictive measures . Good infection control practice is a critical component for success of such a programme . J Hosp Infect, 2003 Feb, 53(2), 85 - 90 Multidisciplinary antimicrobial management and the role of the infectious diseases pharmacist--a UK perspective; Knox K et al.; Improved clinical outcome, patient safety, cost savings and a reduction in the burden of antimicrobial resistance are outcomes associated with optimizing antimicrobial use . Despite this, the misuse of antimicrobials in the hospital setting remains a huge problem . The development of antimicrobial management teams and the promotion of the role of the clinical pharmacist in antimicrobial prescribing are recommended strategies for improving prescribing practice . It is recognized that there is a lack of published evidence-based research looking at the effects of antimicrobial control programmes and there is a need for more data . In the UK, the role of the hospital pharmacist in promoting responsible antimicrobial prescribing has been largely undervalued and needs to be encouraged and formalized in line with current directives . Managerial structures within hospitals need to endorse multidisciplinary antimicrobial management schemes with appropriate authoritative, administrative and information technology support . Nitric Oxide, 2003 Feb, 8(1), 1 - 6 Effect of amidine derivatives on nitric oxide production by Leishmania amazonensis promastigotes and axenic amastigotes; Genestra M et al.; The effects of pentamidine isethionate (reference drug) and N,N'-diphenyl-4-methoxy-benzamidine (test compound) on NO . production by Leishmania amazonensis promastigotes and axenic amastigotes were investigated by measuring nitrite, a by-product of nitric oxide released into culture supernatants . The NO . production by infective promastigotes was inhibited by OCH(3)-amidine in about 23.53% and by pentamidine in only 3.78% . In axenic amastigotes, the inhibition of NO . production by OCH(3)-amidine was significantly higher (52.94%; p=0.01) than that by pentamidine, which inhibited this radical production nonsignificantly (25.29%; p=0.1) . The mechanism of amidine derivatives, as an antimicrobial agent, is unknown . However, other amidines, such as a diamidine (pentamidine), contain chemical structures shared by the guanidino group of the nitric oxide synthase substrate L-arginine, suggesting the possibility of an interaction with this enzyme or electronic factors (substituent constant) that alter physical and chemical properties significant for biological activity. FEBS Lett, 2003 Feb 11, 536(1-3), 215 - 9 Synthetic and structural studies on Pyrularia pubera thionin: a single-residue mutation enhances activity against Gram-negative bacteria; Vila-Perello M et al.; The thionin from Pyrularia pubera (Pp-TH), a 47-residue peptide with four internal disulfide bonds, was efficiently produced by chemical synthesis . Its antimicrobial activity in vitro against several representative pathogens (EC(50)=0.3-3.0 microM) was identical to that of natural Pp-TH . This peptide has a unique Asp(32) instead of the consensus Arg found in other thionins of the same family . In order to evaluate the effect of this mutation, the Arg(32) analogue (Pp-TH(D32R)) was also synthesized and showed a significant increase in antibiotic activity against several Gram-negative bacteria, whereas it retained the same activity against other pathogens . The overall structure of Pp-TH(D32R) was maintained, though a slight decrease in the helical content of the peptide was observed. Enferm Infecc Microbiol Clin, 2003 Feb, 21(2), 93 - 100 {Cyclic rotation of antibiotics . Is all that glitters gold?}; Sandiumenge A et al.; Antibiotic cycling refers to the rotation of antimicrobial agents; that is, one specific agent or class of agents is withdrawn from use during a predefined time period, switched to another, and reintroduced at a later time . This strategy of periodic restriction attempts to reduce the selective pressure that antibiotic agents exert on microbial flora, thereby reducing antimicrobial resistance . Such control of antibiotic use has been proposed as an effective measure for preventing the emergence and spread of resistant pathogens, particularly in areas with high levels of antibiotic pressure . Although the first works on antibiotic cycling were published more than two decades ago, the experience with rotational therapy is limited . Most studies on this subject report intriguing and promising results . Nevertheless, a detailed examination of the literature discloses differences in the objectives proposed, the variables analyzed, and the methods for quantification, making generalization of the results difficult . The association between antibiotic use and emergence of multi-drug resistant pathogens has been extensively demonstrated, but the influence of several factors on the mechanisms of emergence and spread of antibiotic resistance in microorganisms makes it difficult to establish a cause-effect relationship . In this article several methodological considerations are suggested for future studies testing this new antibiotic strategy. Rev Med Brux, 2002, 23 Suppl 2, 93 - 6 {The infective diseases clinic}; Jacobs F et al.; The Clinic of Infectious Diseases was created at Erasme Hospital in 1980 . Its main activity consists in taking care of patients with infectious complications in various hospital departments . Its main scientific contributions concern the evaluation of new treatments, pharmacokinetics of antimicrobial agents and physiopathology of sepsis . The evaluation of the impact of infectious diseases on the appropriateness of antimicrobial therapy and the control of infection is a major contribution of the clinic . Several works concern the study of the immune response in case of infection due to an intracellular pathogen and in response to vaccination. Med Pregl, 2002 Sep-Oct, 55(9-10), 397 - 400 {Treatment of acute upper respiratory tract infections in children}; Roncevic N et al.; INTRODUCTION: Acute respiratory tract infections are the most common diseases of childhood . A preschool child suffers up to 5-7 infections of upper airways during a year . Upper airway infections make 80-90% of all respiratory infections . ETIOLOGY AND TREATMENT: In 75% of all cases respiratory infections are of viral etiology, 15% of bacterial and 10% are caused by mycoplasma, rickettsiae, fungi, parasites . The treatment of respiratory infections includes antimicrobial therapy (causal), relief of symptoms (symptomatic) and application of general principles of child treatment . The choice of antimicrob