Antimicrobial

Ned Tijdschr Tandheelkd, 1996 Jan, 103(1), 3 - 5
{Discoloration of teeth by drugs}; de Wit ME et al.; Since 1979 the Dutch Centre for Monitoring of Adverse Reactions to Drugs received 37 reports of tooth discoloration, attributed to the use of drugs . It concerned sixteen males and 21 females with an average age of respectively twelve and 26 years . Most cases were attributed to the use of amoxicillin (n = 16) and doxycycline or minocycline (n = 7) . Pseudo-discolorations are chiefly caused by antimicrobial agents, possibly by chromogenic precipitates in the pellicle or by overgrowth with chromogenic micro-organisms.

Thorax, 2002 Apr, 57(4), 366 - 71
The pulmonary physician in critical care * 4: Nosocomial pneumonia; Ewig S et al.; Much progress has been made in the understanding of nosocomial pneumonia but important issues in diagnosis and treatment remain unresolved . The controversy over diagnostic tools should be closed . Instead, every effort should be made to increase our ability to make valid clinical predictions about the presence of ventilator associated pneumonia and to establish criteria to guide restricting empirical antimicrobial treatment without causing patient harm . More emphasis must be put on local infection control measures such as routine surveillance of pathogens, definition of controlled policies of antimicrobial treatment, and effective implementation of strategies of prevention.

J Clin Microbiol, 2002 Apr, 40(4), 1346 - 51
Identification of medically relevant Nocardia species with an abbreviated battery of tests; Kiska DL et al.; Identification of Nocardia to the species level is useful for predicting antimicrobial susceptibility patterns and defining the pathogenicity and geographic distribution of these organisms . We sought to develop an identification method which was accurate, timely, and employed tests which would be readily available in most clinical laboratories . We evaluated the API 20C AUX yeast identification system as well as several biochemical tests and Kirby-Bauer susceptibility patterns for the identification of 75 isolates encompassing the 8 medically relevant Nocardia species . There were few biochemical reactions that were sufficiently unique for species identification; of note, N . nova were positive for arylsulfatase, N . farcinica were positive for opacification of Middlebrook 7H11 agar, and N . brasiliensis and N . pseudobrasiliensis were the only species capable of liquefying gelatin . API 20C sugar assimilation patterns were unique for N . transvalensis, N . asteroides IV, and N . brevicatena . There was overlap among the assimilation patterns for the other species . Species-specific patterns of susceptibility to gentamicin, tobramycin, amikacin, and erythromycin were obtained for N . nova, N . farcinica, and N . brevicatena, while there was overlap among the susceptibility patterns for the other isolates . No single method could identify all Nocardia isolates to the species level; therefore, a combination of methods was necessary . An algorithm utilizing antibiotic susceptibility patterns, citrate utilization, acetamide utilization, and assimilation of inositol and adonitol accurately identified all isolates . The algorithm was expanded to include infrequent drug susceptibility patterns which have been reported in the literature but which were not seen in this study.

Med Pregl, 2001 Nov-Dec, 54(11-12), 547 - 51
{Use of aminopenicillins in hospitals and outpatient facilities}; Mikic SS et al.; INTRODUCTION: Ampicillins are thought to be the most widely used antibiotics . Although ampicillin is included in the WHO list of essential drugs, its per-oral administration is not recommended, whereas amoxicillin is recommended due to its identical antimicrobial spectrum and better pharmacokinetic characteristics . Instead, per oral form of amoxicillin is recommended because of its identical antimicrobial spectrum and better pharmacokinetic characteristics . MATERIAL AND METHODS: Drug utilization evaluation of aminopenicillins (ampicillin and amoxcillin) was performed at the Clinic for Infectious Diseases . Clinical Center of Novi Sad and in the Outpatient Health Care Center, Novi Sad "Liman" (Department of General Practice Children's Health Care Department and Ear, Nose and Throat Department) during one calendar month in the year 2000 . RESULTS: The use of aminopenicillin was 5.1 Defined Daily Doses per 100 bed-days (5.1 DDD/100 BD) at the Clinic for Infectious Diseases . Ampicillin was used in 37.64% of patients and amoxicillin in 13.13% . In Outpatient Health Care Center (OHCC), Department of General Practice, aminopenicillins were prescribed in 1.02 Defined Daily Doses per 1000 inhabitants per day (DDD/1000 inh/day); ampicillin being prescribed in 24.51% and amoxicillin in 75.49%, and it is an optimal ratio . In Children's Health Care Department, OHCC, in children older than 14 years, aminopenicillins were prescribed in 0.37 pediatric DDD/1000 inh/day (ampicillin 40.5%, amoxicillin 59.5%) . In the same department, in the age group between 3 and 14 years it was 0.31 pediatric DDD/1000 inh/day (ampicillin 22.5%, amoxicillin 77.5%), while in the age group from 1 to 3 years there were 0.006 pediatric DDD/1000 inh/day prescribed (amoxicillin 100%) . At the Ear, Nose and Throat Department, OHCC aminopenicillins were prescribed in 0.02 DDD/1000 inh/day (amoxicillin 100%) . CONCLUSIONS: Our research showed a change in habits in regard to prescriptions towards the recommended protocol . Oral administration of ampicillin has decreased, especially in comparison to the earlier period in which it had dominated in our primary health care.

East Afr Med J, 2001 Oct, 78(10), 518 - 22
Antimicrobial susceptibility and plasmids from Escherichia coli isolated from rats; Gakuya FM et al.; OBJECTIVES: To determine if antimicrobial resistance occurs in E . coli isolated from rats and if this resistance is transferable via plasmids . METHODS: Sixty Escherichia coli isolates obtained from 215 rats trapped in and around Nairobi, Kenya, were analysed for antimicrobial susceptibility to eleven commonly used antimicrobials . Plasmid DNA analysis and in-vitro conjugation tests were conducted on twenty two resistant isolates . RESULTS: A total of 12 (20%) E . coli were resistant to at least one of the commonly used drugs including ampicillin, sulphamethoxazole and streptomycin . Eight (13.3%) isolates were multidrug resistant . The drug resistant E . coli fell into five plasmid profile groups with plasmids ranging between two and 98 megadaltons (Mda) . Resistance to ampicillin was transferable . CONCLUSION: The results of this study show that rats from the study area may form an important reservoir for drug-resistant E . coli that could pose a public health hazard.

Microsc Res Tech, 2002 Apr 1, 57(1), 23 - 7
Identification, characterization, and physiological actions of factor H as an adrenomedullin binding protein present in human plasma; Pio R et al.; A recently discovered adrenomedullin binding protein has been characterized as complement factor H, an important regulator of the complement cascade . This review will describe the evidence that led to the identification of factor H as an adrenomedullin binding protein and will address the implications that such binding has in the radioimmunoassay of AM in plasma . We will also describe the possible physiological implications of AM binding: namely, factor H suppresses the antimicrobial activity of AM, enhances AM-mediated induction of cyclic-AMP in rat fibroblasts, and augments the AM-mediated growth of a human cancer cell line . These initial studies suggest that factor H may be an important factor in the regulation of AM physiology . The elucidation of the mechanisms that modulate AM activity will be necessary for the understanding of the role of AM in normal and pathological conditions .

J Infect Dis, 2002 Mar 15, 185(6), 797 - 804 Epub 2002 Feb 20.
Borrelia burgdorferi are susceptible to killing by a variety of human polymorphonuclear leukocyte components; Lusitani D et al.; The killing of Borrelia burgdorferi by intact human polymorphonuclear leukocytes (PMNL) and by individual PMNL components was compared . Intact PMNL killed B . burgdorferi 6.5-fold more efficiently and 5-fold more completely when spirochetes were opsonized with specific antibodies . U-cytoplasts, which have activatable oxidase, killed opsonized B . burgdorferi with an efficiency similar to that of intact PMNL in killing unopsonized B . burgdorferi . Although B . burgdorferi were susceptible to H(2)O(2) and nitric oxide, PMNL lysates killed B . burgdorferi nearly as well as intact PMNL killed opsonized B . burgdorferi, suggesting a critical role for granule contents . B . burgdorferi were killed by the PMNL antimicrobial components elastase, LL-37, bactericidal/permeability-increasing protein, and human neutrophil peptide-1 . B . burgdorferi had limited susceptibility to killing by lysozyme and were not killed by azurocidin, proteinase 3, or lactoferrin . The efficient killing of B . burgdorferi by a variety of PMNL mechanisms highlights the paradoxical persistence of spirochetes in vivo.

Arq Gastroenterol, 2001 Jul-Sep, 38(3), 203 - 6
Triple therapy with clarithromycin, amoxicillin and omeprazole for Helicobacter pylori eradication in children and adolescents; Kawakami E et al.; BACKGROUND: Helicobacter pylori infection presents high prevalence in developing countries, but there are few pediatric assays evaluating antimicrobial treatment . OBJECTIVE: The aim of this study was to investigate Helicobacter pylori eradication rate using a short regimen (7 and 10 days) of triple therapy with clarithromycin, amoxicillin and omeprazole . PATIENTS AND METHODS: Twenty-five Hp positive patients who presented severe epigastralgia, were submitted to antimicrobial treatment with amoxicillin (50 mg/kg/day--maximum dose 1 g bid), clarithromycin (30 mg/kg/day--maximum dose 500 mg bid) and omeprazole (0.6 mg/kg/day--maximum dose 20 mg bid) during 7 or 10 days . After 2 months, clinical symptoms were evaluated and gastric biopsies were taken to test Hp eradication . RESULTS: Overall eradication rate was achieved in 16/25 patients (64%--IC(95% = 45-83%), in 11/15 (73%--IC(95%) = 51-95%) patients who used 10 days therapy course and in 5/10 (50%--IC(95%) = 19-81%) who used 7 days therapy course . Eradication drugs were well accepted and adverse effects were reported in two patients (8%) . CONCLUSIONS: This triple therapy regimen had moderate efficacy (64%) . The data suggests that 10 days therapy course achieves better eradication rate (73%) than 7 days course (50%) to treat Hp infection in our population.

Compend Contin Educ Dent Suppl, 2001, (32), 4 - 6;quiz 22
Recurrent oral ulcers--an overview; Gaffar A; Recurrent oral ulcers (ROUs) are the most common oral mucosal disease . The etiology of ROUs is complex . The factors include mechanical trauma, genetics, stress, smoking, and viral and bacterial infections . Treatment modalities depend on the differential diagnosis of ROUs and could consist of antimicrobial agents, anti-inflammatory agents, immunomodulators, or over-the-counter medications . New therapy available in the form of a coating polymer, Colgate ORABASE Soothe.N.Seal, is clinically proven to provide rapid relief and healing of ROUs.

Arch Pediatr, 2002 Feb, 9(2), 130 - 5
{Acquisition of secondary resistance after failure of a first treatment of Helicobacter pylori infection in children}; Kalach N et al.; AIMS: To assess the frequency of acquisition of secondary Helicobacter pylori resistant-strains after a first course of antimicrobial treatment . PATIENTS AND METHODS: A retrospective study was performed during the 1994-2000 period, in 15 girls and eight boys, mean age 10.9 +/- 4.8 years (1.4-17 years), with Helicobacter pylori gastritis (culture and antimicrobial susceptibility) presenting a failure of first course treatment, with during one week a proton pump inhibitor and amoxicillin together with either clarithromycin (n = 14) or metronidazole (n = 9) . Two endoscopies were performed, the first at the time of diagnosis and the second after the failure of bacterial eradication demonstrated by a positive 13C urea breath test six weeks after the end of treatment . Antimicrobial susceptibility of all Helicobacter pylori strains was tested after each endoscopy and before starting a second course of the treatment . RESULTS: Comparison of antimicrobial susceptibility before and after the first course of treatment showed that Helicobacter pylori strains were all sensitive to amoxicillin, clarithromycin-resistant in eight children (34.7%) before treatment vs 12 (52.1%) after treatment, p = 0.42, ns, metronidazole-resistant in 13 (56.5%) vs 12 (52.1%), p = 0.80, ns, and both clarithromycin and metronidazole-resistant in four (17.3%) vs seven (30.4%), p = 0.63, ns . Among the 14 children treated by a triple therapy including clarithromycin, three (21.4%) developed a secondary resistance to clarithromycin and in one metronidazole resistance was no more detected . Among the nine children treated with a triple therapy including metronidazole, none developed a secondary resistance to metronidazole and one developed a secondary resistance to clarithromycin . CONCLUSION: This study shows the absence of amoxicillin-resistant strains, a high initial clarithromycin-resistant strains level (primary resistance), increasing after a first course of treatment, and for metronidazole a high initial level of resistance not influenced by treatment . Secondary clarithromycin-resistance of Helicobacter pylori strains following the first course of treatment could account for failure of bacterial eradication and suggests the importance of antimicrobial susceptibility.

Planta Med, 2002 Mar, 68(3), 277 - 81
Antimicrobial activity of 9-O-acyl- and 9-O-alkylberberrubine derivatives; Kim SH et al.; For the structure-activity relationship study on berberrubine derivatives, a series of compounds bearing 9-O-acyl- and 9-O-alkyl-substituents were synthesized and tested for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi . Octanoyl, decanoyl, lauroyl derivatives among the acyl analogs and hexyl, heptyl, octyl, nonyl, decyl, undecyl derivatives among the alkyl analogs showed strong antimicrobial activity against Gram-positive bacteria and fungi . As a whole, alkyl analogs were more active than acyl analogs for antimicrobial activity . Synthesized derivatives had no activity on Gram-negative bacteria . Too short or too long substituents decreased activity . These results suggest that the presence of lipophilic substituents with moderate sizes might be crucial for the optimal antimicrobial activity.

Eur J Vasc Endovasc Surg, 2002 Mar, 23(3), 241 - 3
Bacterial colonisation of Doppler probes on vascular surgical wards; Kibria SM et al.; AIM: hospital acquired infections cost the NHS 1 pound sterling billion each year and medical equipment may act both as source and vector of nosocomial infection . This study examined bacterial contamination of Doppler ultrasound probes (USP) in routine use on vascular surgical wards in six hospitals and the knowledge of staff about the potential for cross infection from contaminated probes . METHODS: probe head impressions and swab cultures of probe holders were plated on mannitol salt agar before and after cleaning with a paper towel . Putative S . aureus isolates were identified to species level and susceptibility to selected antimicrobials tested . Concurrently, junior medical staff were surveyed about probe cleaning protocols . RESULTS: methicillin susceptible S . aureus was isolated from 2/21 (10%) with near confluent bacterial growth from six others (28%) . The latter may have obscured low numbers of S . aureus . Further since swabs were plated without prior enrichment culture, it is likely that contamination with S . aureus might have been underestimated . No positive cultures were obtained after wiping the USP with a paper towel . 22/23 (95%) junior doctors failed to clean the USP prior to use . CONCLUSION: USP contamination with pathogenic bacteria occurs under "in-use" conditions and junior medical staff are unaware of simple measures to prevent this . Strict guidelines for USP cleaning between patient use should, therefore, be adopted particularly when monitoring postoperative graft patency .

Eur J Clin Microbiol Infect Dis, 2002 Jan, 21(1), 53 - 5
Xylitol concentrations in the saliva of children after chewing xylitol gum or consuming a xylitol mixture; Tapiainen T et al.; Xylitol prevents otitis media when given to children regularly five times per day . To find a more convenient dosing schedule, an enzymatic assay was used to measure xylitol concentrations in the saliva of 65 children after giving them xylitol chewing gum or syrup in doses equal to those used in clinical trials . Although concentrations high enough to have an antimicrobial effect were attained, the xylitol disappeared from the saliva within 15 min . This finding indicates that high peak concentrations are more important for efficacy than the amount of time the xylitol concentration exceeds that needed to produce an antimicrobial effect . A schedule with the same single doses given less frequently could be clinically effective in preventing otitis media.

Nature, 2002 Apr 11, 416(6881), 640 - 4 Epub 2002 Mar 24.
The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein; Gottar M et al.; The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body . The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway . Loss-of-function mutations in either pathway reduce the resistance to corresponding infections . The link between microbial infections and activation of these two pathways has remained elusive . The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA) . PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members . Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections . By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene . The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila.

Mol Hum Reprod, 2002 Apr, 8(4), 341 - 9
Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells; King AE et al.; The natural antibiotic molecules, beta-defensins 1 and 2 (HBD1/2) and secretory leukocyte protease inhibitor (SLPI), have an important role in mucosal defence and are present in the uterus . This study details their regulation in primary endometrial epithelial cells and in two endometrial cell lines (MFE/HES) . Cells were treated with proinflammatory molecules and mimics of infection {lipopolysaccharide (LPS) and lipoteichoic acid (LTA)} . mRNA for HBD1, HBD2 and SLPI was detected in primary endometrial epithelial cells using real-time quantitative PCR . HBD1 mRNA was present at very low levels preventing conclusive study of its regulation . However, HBD2 mRNA expression was increased by interferon-gamma, interleukin (IL)-1beta alone and IL-1beta+tumour necrosis factor (TNF)-alpha . SLPI mRNA was not affected by proinflammatory mediators, although protein levels fell in the presence of IL-1beta+TNFalpha . LPS had little effect on antimicrobial expression . However, there was a trend towards increased expression with LTA treatment for 4-8 h . Antimicrobial expression in endometrial cell lines was similar to that in primary cells, although SLPI was increased by IL-1beta+TNFalpha treatment . These results suggest that in endometrium some natural antibiotics (e.g . SLPI) may be constitutively expressed providing a basal level of protection, while others (e.g . HBD2) are inducible allowing maximal antimicrobial activity during infection . Natural antimicrobials will have an important role in endometrium in protecting against infection.

Brain, 2002 Apr, 125(Pt 4), 722 - 31
Minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease; Tikka TM et al.; CSF from patients with motor neurone disease (MND) has been reported to be toxic to cultured primary neurones . We found that CSF from MND patients homozygous for the D90A CuZn-superoxide dismutase (CuZn-SOD) mutation, patients with sporadic MND and patients with familial MND without CuZn-SOD mutations significantly increased apoptosis and reduced phosphorylation of neurofilaments in cultured spinal cord neurones when compared with the effects of CSF from patients with other neurological diseases . Exposure of spinal cord cultures to MND CSF also triggered microglial activation . The toxicity of MND CSF was independent of the presence of the CuZn-SOD mutation, and it did not correlate with gelatinase activity or the presence of immunoglobulin G autoantibodies in the CSF . The concentrations of glutamate, aspartate and glycine in MND CSF were not elevated . Antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptors prevented the toxic CSF-induced neuronal death but not microglial activation, whereas minocycline, a tetracycline derivative with anti-inflammatory potential independent of antimicrobial activity, reduced both the apoptotic neuronal death and microglial activation . We conclude that the cytotoxic action of CSF is prevalent in all MND cases and that microglia may mediate the toxicity of CSF by releasing excitotoxicity-enhancing factors.

Salud Publica Mex, 2002 Jan-Feb, 44(1), 26 - 32
Carriage of antibiotic-resistant pneumococci in a cohort of a daycare center; Gomez-Barreto D et al.; OBJECTIVE: To define epidemiologic relationships to determine the prevalence and potential risk factors for nasopharyngeal colonization by antibiotic-resistant pneumococci, their serotypes and their antibiotic susceptibility patterns in children attending a daycare center (DCC) . MATERIAL AND METHODS: A prospective cohort study was conducted among children (n = 53) attending the DCC at Hospital Infantil de Mexico Federico Gomez, which is staffed by 20 employees . Patients were enrolled in the study during a two-year period from September 1997 to September 1999 . All the participants were followed prospectively, swabbing them every four months . The strains recovered were typed and screened for susceptibility to several antibiotics . The daycare records were reviewed also . Odds ratios and fisher's exact test: or chi square test of significance were computed from contingency tables as appropriate . Exact 95% confidence intervals were computed for odds ratios . Data analysis was performed using Epi statistics program version 6.04 a . RESULTS: Pneumococci were recovered from 45/53 of the infants at one or more visits . A total of 178 isolates were carried . The carriage rate was 47% . Only 7 adults acquired pneumococci during the study . Types 6, 14, 19 and 23 were prevalent and represented 77% of the total . Antibiotic-resistant strains were higher to penicillin and erythromycin . CONCLUSIONS: Children were frequent carriers of pneumococci, the rate of carriage was high in infancy and tended to decrease with age . The types commonly carried by children were the same as those causing invasive disease . There is a high proportion of carriers with antibiotic-resistant S . pneumoniae strains . Children who have had frequent antimicrobial courses are at particular risk.

J Biol Chem, 2002 Jun 21, 277(25), 22656 - 61 Epub 2002 Mar 21.
The major conformational IgE-binding epitopes of hevein (Hev b6.02) are identified by a novel chimera-based allergen epitope mapping strategy; Karisola P et al.; A novel approach to localize and reconstruct conformational IgE-binding epitope regions of hevein (Hev b6.02), a major natural rubber latex allergen, is described . An antimicrobial protein (AMP) from the amaranth Amaranthus caudatus was used as an immunologically non-IgE-binding adaptor molecule to which terminal or central parts of hevein were fused . Hevein and AMP share a structurally identical core region but have different N-terminal and C-terminal regions . Only 1 of 16 hevein-allergic patients showed weak IgE binding to purified native or recombinant AMP . Chimeric AMP with the hevein N terminus was recognized by IgE from 14 (88%) patients, and chimeric AMP with the hevein C terminus was recognized by IgE from 6 (38%) patients . In contrast, chimeric AMP containing the hevein core region was recognized by IgE from only two patients . When both the N-terminal and C-terminal regions of hevein were fused with the AMP core, IgE from all 16 patients bound to the chimera . This chimera was also able to significantly inhibit (>70%) IgE binding to the native hevein . On the contrary, linear synthetic peptides corresponding to hevein regions in the AMP chimeras showed no significant IgE binding capacity in either enzyme-linked immunosorbent assay or inhibition enzyme-linked immunosorbent assay . These results suggest that the IgE binding ability of hevein is essentially determined by its N-terminal and C-terminal regions and that major IgE-binding epitopes of hevein are conformational . The chimera-based epitope mapping strategy described here provides a valuable tool for defining structural epitopes and creating specific reagents for allergen immunotherapy.

Microbes Infect, 2002 Mar, 4(3), 361 - 72
Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity; Ramanathan B et al.; Antimicrobial peptides are important host-defense molecules of innate immunity . Cathelicidins are a diverse family of potent, rapidly acting and broadly effective antimicrobial peptides, which are produced by a variety of cells . This review examines the classification, antimicrobial spectrum, mechanism of action, and regulation of cathelicidins.

Microbes Infect, 2002 Mar, 4(3), 325 - 31
Outer membrane proteins: key players for bacterial adaptation in host niches; Lin J et al.; Outer membrane proteins (OMPs) of Gram-negative bacteria have diverse functions and are directly involved in the interaction with various environments encountered by pathogenic organisms . Thus, OMPs represent important virulence factors and play essential roles in bacterial adaptation to host niches, which are usually hostile to invading pathogens . Understanding the structure and functions of bacterial OMPs will facilitate the design of antimicrobial drugs and vaccines . In this paper, we will present a brief review on OMPs that contribute to bacterial adaptive responses including iron uptake, antimicrobial peptide resistance, serum resistance, and drug/bile resistance.

J Nat Prod, 2002 Mar, 65(3), 364 - 7
Bioactive metabolites from a marine-derived strain of the fungus Emericella variecolor; Malmstrom J et al.; From a marine-derived strain of the fungus Emericella variecolor, varitriol (1), varioxirane (2), dihydroterrein (3), and varixanthone (4), besides the known mold metabolites ergosterol, terrein, shamixanthone, and tajixanthone hydrate, were identified . The chemical structures of 1-4 were established by means of spectroscopic techniques and some chemical transformations . In the NCI's 60-cell panel, varitriol (1) displayed increased potency toward selected renal, CNS, and breast cancer cell lines . Varixanthone (4) showed antimicrobial activity.

Biochem Cell Biol, 2002, 80(1), 65 - 74
Important structural features of 15-residue lactoferricin derivatives and methods for improvement of antimicrobial activity; Strom MB et al.; This review focuses on important structural features affecting the antimicrobial activity of 15-residue derivatives of lactoferricins . Our investigations are based on an alanine-scan of a 15-residue bovine lactoferricin derivative that revealed the absolute necessity of two tryptophan residues for antimicrobial activity . This "tryptophan-effect" was further explored in homologous derivatives of human, caprine, and porcine lactoferricins by the incorporation of one additional tryptophan residue, and by increasing the content of tryptophan in the bovine derivative to five residues . Most of the resulting peptides display a substantial increase in antimicrobial activity . To identify which molecular properties make tryptophan so effective, a series of bovine lactoferricin derivatives were prepared containing non-encoded unnatural aromatic amino acids, which represented various aspects of the physicochemical nature of tryptophan . The results clearly demonstrate that tryptophan is not unique since most of the modified peptides were of higher antimicrobial potency than the native peptide . The size and three-dimensional shape of the inserted "super-tryptophans" are the most important determinants for the high antimicrobial activity of the modified peptides . This review also describes the use of a "soft-modeling" approach in order to identify important structural parameters affecting the antimicrobial activity of modified 15-residue murine lactoferricin derivatives . This QSAR-study revealed that the net charge, charge asymmetry, and micelle affinity of the peptides were the most important structural parameters affecting their antimicrobial activity.

Biochem Cell Biol, 2002, 80(1), 49 - 63
Towards a structure-function analysis of bovine lactoferricin and related tryptophan- and arginine-containing peptides; Vogel HJ et al.; The iron-binding protein lactoferrin is a multifunctional protein that has antibacterial, antifungal, antiviral, antitumour, anti-inflammatory, and immunoregulatory properties . All of these additional properties appear to be related to its highly basic N-terminal region . This part of the protein can be released in the stomach by pepsin cleavage at acid pH . The 25-residue antimicrobial peptide that is released is called lactoferricin . In this work, we review our knowledge about the structure of the peptide and attempt to relate this to its many functions . Microcalorimetry and fluorescence spectroscopy data regarding the interaction of the peptide with model membranes show that binding to net negatively charged bacterial and cancer cell membranes is preferred over neutral eukaryotic membranes . Binding of the peptide destabilizes the regular membrane bilayer structure . Residues that are of particular importance for the activity of lactoferricin are tryptophan and arginine . These two amino acids are also prevalent in "penetratins", which are regions of proteins or synthetic peptides that can spontaneously cross membranes and in short hexapeptide antimicrobial peptides derived through combinatorial chemistry . While the antimicrobial, antifungal, antitumour, and antiviral properties of lactoferricin can be related to the Trp/Arg-rich portion of the peptide, we suggest that the anti-inflammatory and immunomodulating properties are more related to a positively charged region of the molecule, which, like the alpha- and beta-defensins, may act as a chemokine . Few small peptides are involved in as wide a range of host defense functions as bovine and human lactoferricin.

Biochem Cell Biol, 2002, 80(1), 109 - 12
Bovine lactoferrin and lactoferricin derived from milk: production and applications; Tomita M et al.; Bovine lactoferrin is produced on an industrial scale from cheese whey or skim milk . The safety of purified lactoferrin has been confirmed from the results of a reverse mutation test using bacteria, a 13-week oral repeated-dose toxicity study in rats, and clinical studies . In order to apply active lactoferrin to various products, a process for its pasteurization was developed . Subsequently, lactoferrin has been used in a wide variety of products since it was first added to infant formula in 1986 . A pepsin hydrolysate of lactoferrin is also used in infant formula . This hydrolysate contains a potent antimicrobial peptide named lactoferricin that is derived from the lactoferrin molecule by pepsin digestion . Semilarge-scale purification of lactoferricin can be performed by hydrophobic interaction chromatography . Lactoferricin also exhibits several biological actions and appears to be the functional domain of lactoferrin . Recent studies have demonstrated that oral administration of lactoferrin or lactoferricin exerts a host-protective effect in various animals and in humans . The results of these studies strongly suggest that the effects of oral lactoferrin are mediated by modulation of the immune system . Further elucidation of the clinical efficacy and mechanism of action of lactoferrin will increase the value of lactoferrin-containing products.

Compend Contin Educ Dent, 1999, 20(4 Suppl), 4 - 12; quiz 34
The supplemental use of antibiotics in periodontal therapy; Walker C; Many antibiotics and other chemotherapeutic agents have been used as adjuncts to mechanical periodontal therapy with mixed results . This article reviews the clinical and microbial results obtained after the systemic administration of tetracyclines, penicillins, clindamycin, and metronidazole, as well as the combination of metronidazole and Augmentin as adjuncts to conventional periodontal treatment . The major adverse effects associated with each of these antibiotics are given, as well as the potential for the emergence of antibiotic resistance in the periodontal flora . Recently, the introduction of a new generation of controlled-release, locally applied antimicrobial agents provides the clinician with the opportunity to treat individual periodontal sites with high concentrations of medication . The clinical effects obtained from multicenter clinical trials with PerioChip, which contains chlorhexidine, and with Atridox, which contains doxycycline, are summarized . Finally, suggestions are given both for the selection of an antimicrobial agent and for minimizing the development of antibiotic resistance in the periodontal flora.

Compend Contin Educ Dent, 1999, 20(4 Suppl), 13 - 8; quiz 34-5
Local delivery of antimicrobials: a new era in the treatment of adult periodontitis; Killoy WJ; This article discusses the principles, products, and techniques currently available for local delivery of antimicrobials in the treatment of adult periodontitis . Four principles provide the scientific basis for the treatment of periodontitis: it is caused by bacteria; it cannot be cured, but it can be controlled; clinicians cannot remove all the plaque and calculus; and periodontitis reinfects . This article stresses how the local delivery of antimicrobials can help the clinician achieve the goals of arresting the disease and maintaining the disease in the arrested or controlled state . Rationales for reevaluating the treated patient and treatment options are presented . Local-delivery systems are reviewed, stressing those available in the United States . Pharmacokinetics, multicenter randomized trials, and techniques are presented.

Dev Comp Immunol, 2002 Jun, 26(5), 471 - 9
Activity of antimicrobial skin peptides from ranid frogs against Batrachochytrium dendrobatidis, the chytrid fungus associated with global amphibian declines; Rollins-Smith LA et al.; Accumulating evidence suggests that a chytrid fungus, Batrachochytrium dendrobatidis, is responsible for recent declines in amphibian populations in Australia, Central America, Europe, and North America . Because the chytrid infects the keratinized epithelium of the skin, we investigated the possible role of antimicrobial peptides produced in the skin as inhibitors of infection and growth . We show here that 10 peptides representing eight families of peptides derived from North American ranid frogs can effectively inhibit growth of this chytrid . The peptides are members of the ranatuerin-1, ranatuerin-2, esculentin-1, esculentin-2, brevinin-2, temporin, palustrin-3, and ranalexin families . All the tested peptides inhibit growth of mature fungal cells at concentrations above 25 microM, and some of them inhibit at concentrations as low as 2 microM . A comparison of the sensitivity of infectious zoospores with that of mature cells showed that the zoospores are inhibited at significantly lower concentrations of peptides . To determine whether cold temperature interferes with the inhibitory effects of these peptides, we tested their effectiveness at both 22 and 10 degrees C . Although the peptides inhibit at both temperatures, they appear to be more effective against zoospores at the lower temperature . These results suggest that the ranid frogs have, within their repertoire of antimicrobial substances, a number of skin peptides that should be a deterrent to chytrid infection . This may provide some natural resistance to infection, but if environmental factors inhibit the synthesis and release of the skin peptides, the pathogen could gain the advantage.

Dev Comp Immunol, 2002 Jun, 26(5), 445 - 59
Induction of nitric oxide and respiratory burst response in activated goldfish macrophages requires potassium channel activity; Stafford JL et al.; Potassium channel activity is important for modulating mammalian macrophage antimicrobial functions . The involvement of potassium channels in mediation of immune cell function in lower vertebrates, such as teleost, has not been explored . Since relatively little is known about the types of potassium channels present in fish macrophages, pharmacological blockers with broad ranges of activity were tested: 4-aminopyridine (4-AP), quinine, and tetraethylammonium chloride (TEA) . The potassium channel blockers inhibited reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) production by goldfish macrophages activated with bacterial lipopolysaccharide (LPS) and/or macrophage activating factor (MAF)-containing supernatants . Quinine was the most potent inhibitor with an IC(50) of 50 microM, while the other blockers, 4-AP and TEA, had IC(50) of 1.2 and 0.6mM, respectively . A reversible depolarization of the goldfish macrophage plasma membrane potential (Vm) was observed following treatments with potassium channel blockers, and was related to transcriptional changes in the inducible nitric oxide synthase gene (iNOS) . Down-regulation of antimicrobial activities and depolarization of the goldfish macrophage plasma membrane were not a consequence of reduced cell number or viability, suggesting that potassium channels are required for generation of appropriate goldfish macrophage antimicrobial functions.

Cell Microbiol, 2002 Mar, 4(3), 167 - 76
Association of a macrophage galactoside-binding protein with Mycobacterium-containing phagosomes; Beatty WL et al.; Mycobacteria reside intracellularly in a vacuole that allows it to circumvent the antimicrobial environment of the host macrophage . Although the mycobacterial phagosome exhibits selective fusion with vesicles of the endosomal system, identification of host and bacterial factors associated with phagosome bio-genesis is limited . To identify these potential factors, mAbs were generated to a membrane preparation of mycobacterial phagosomes isolated from M . tuberculosis-infected macrophages . A mAb recognizing a 32-35 kDa macrophage protein associated with the phagosomal membrane of Mycobacterium was identified . N-terminal sequence analysis identified this protein as Mac-2 or galectin-3, a galactoside-binding protein of macrophages . Galectin-3 (gal-3) was shown to accumulate in Mycobacterium-containing phagosomes during the course of infection . This accumulation was specific for phagosomes containing live mycobacteria and occurred primarily at the cytosolic face of the phagosome membrane . In addition, bind-ing of gal-3 to mycobacterial phosphatidylinositol mannosides (PIMs) demonstrated a novel interaction between host carbohydrate-binding proteins and released mycobacterial glycolipids . Infection of macrophages from gal-3-deficient mice indicated that the protein did not play a role in infection in vitro . In contrast, infection of gal-3-deficient mice revealed a reduced capacity to clear late but not early infection.

Biochem Biophys Res Commun, 2002 Mar 29, 292(2), 441 - 8
Production of antiviral and antitumor proteins MAP30 and GAP31 in cucurbits using the plant virus vector ZYMV-AGII; Arazi T et al.; ZYMV-AGII (zucchini yellow mosaic virus-AGII) is a recombinant nonpathogenic potyvirus-based vector system for the expression of foreign genes in cucurbit plants and their edible fruits, including squash, cucumber, melon, watermelon, and pumpkin . MAP30 (Momordica anti-HIV protein, 30 kDa) and GAP31 (Gelonium anti-HIV protein 31 kDa) are multifunctional plant proteins with activity against HIV-1 virus . These proteins are also effective against other viruses, tumor cells, and microbes . We report here the production and characterization of biologically active MAP30 and GAP31 in squash plant by expression of their genes using the ZYMV-AGII vector . Recombinant expressed MAP30 and GAP31 exhibit comparable antiviral, antitumor, and antimicrobial activities as their counterparts from their original plant sources, with EC(50)s in the ranges of 0.2-0.3 nM for HIV-1 . These results demonstrate for the first time the amplification and production of therapeutic proteins, MAP30 and GAP31, in common vegetables . This provides valuable alternative food sources of these antiviral, antitumor, and antimicrobial agents for therapeutic applications . (c)2002 Elsevier Science (USA).

Nat Rev Immunol, 2001 Nov, 1(2), 135 - 45
Toll-like receptors and innate immunity; Medzhitov R; Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects . In mammals, these receptors have evolved to recognize conserved products unique to microbial metabolism . This specificity allows the Toll proteins to detect the presence of infection and to induce activation of inflammatory and antimicrobial innate immune responses . Recognition of microbial products by Toll-like receptors expressed on dendritic cells triggers functional maturation of dendritic cells and leads to initiation of antigen-specific adaptive immune responses.

Kekkaku, 2002 Feb, 77(2), 79 - 86
{CT diagnosis of pulmonary infectious diseases}; Murayama S; Generally, the patient's inflammatory reaction is obvious, and the characteristic infiltrative shadow as pneumonia in the chest radiograph is recognized, no more imaging study is needed . However, when (1) radiographic finding is uncommon as a pneumonia; (2) antimicrobial drug treatment is ineffective; or (3) stenosis of central bronchi causing pneumonia by lung cancer and so on is suspicious, more precise imaging information of computed tomography (CT) is necessary . Recently, high resolution CT of lung disease as a new diagnostic method has been introduced, and diagnostic efficacy of CT has markedly advanced . Although the high resolution CT diagnosis based on the minute anatomy of the lung is also applied for the pulmonary infectious disease, their analysis and arrangement is not yet established since a large number of pathogens and various images exist . In reading CT films, it is necessary to consider patient's immune status . Infectiosity and size of the pathogen must be also considered . In this manuscript, CT imaging characteristics of lung infectious diseases are clarified by taking these points into account.

Kekkaku, 2002 Feb, 77(2), 61 - 6
{Interpretive compatibility of antimycobacterial susceptibility for Mycobacterium tuberculosis determined by proportion test method on egg-based Ogawa media and broth microdilution test, BrothMIC MTB}; Higa M et al.; The antimycobacterial susceptibility test method newly proposed by the Japanese Society for Tuberculosis, a proportion method on egg-based Ogawa media, was evaluated in comparison with microdilution test for Mycobacterium tuberculosis complex, BrothMIC MTB-1 (Kyokuto Pharmaceutical Inc., Tokyo) . In the evaluation, five antimicrobial agents, streptomycin, ethambutol, kanamycin, isoniazid and rifampicin were included . Through repeated testings of the three reference strains against five antimicrobial agents, both test methods were found to be highly precise . All the minimum inhibitory concentrations (MICs) determined by BrothMIC MTB fell within 3 log2 dilutions, however a total of 11 MICs resulted in indeterminate(I) interpretations . Whereas, all the test results by a proportion method on Ogawa media were comparable to the expected interpretations . However, three of 48 testings resulted in undeterminable interpretations due to insufficient growth on the growth control media . A total of 127 clinical isolates of M . tuberculosis complex were tested by both methods, and 89 to 90% of the test results were comparable with each other in category interpretations . However, 7.1 to 9.4% of MICs determined by BrothMIC MTB resulted in indeterminate(I), and 0.8 to 3.1% of discrepant interpretations were observed . In conclusion, both test methods were highly precise and comparable in determining antimycobacterial susceptibility for M . tuberculosis complex . Several advantages and disadvantages in each test method were discussed.

J Vet Pharmacol Ther, 2001 Dec, 24(6), 433 - 8
Comparative studies on Polyferm and Fermosorb, two oral (ferment + sorbent) - type preparations designed for therapy/prophylaxis of intestinal infections in animal neonates; Biziulevicius GA et al.; Polyferm and Fermosorb are oral acid resistant antimicrobial enzyme preparations designed specifically for therapy/prophylaxis of intestinal infections in animal neonates . Both are authorized for use throughout the former Soviet Union, but until now only Fermosorb is being applied on a large scale . The comparative studies on these two preparations, described in this paper, were carried out in order to find differences between the preparations . Characteristics that were compared included stability of the preparations in acidic environment as well as in storage (in vitro studies), and their efficacy for the treatment and prophylaxis of colibacillosis in newborn calves (in vivo studies) . Results of in vitro studies revealed that proteolytic enzymes of Polyferm (as well as lytic enzymes of Fermosorb) were suitably (and in a very similar magnitude) protected from the influence of the acidic environment . The complete enzyme activity retention period in storage at room temperature of Polyferm and Fermosorb was equally high (5 years) . In vivo studies performed on 2000 calves revealed that both preparations were highly effective and, although the efficacy of Polyferm was a bit lower than that of Fermosorb (93.6% vs . 95.0%, 94.6% vs . 95.8% for therapy and prophylaxis of colibacillosis, respectively), no statistically significant differences in the number of Polyferm vs . Fermosorb cured/protected animals were found . It is concluded that there were no reasons, other than the lack of supportive advertising materials, that might impede the utility of Polyferm.

J Vet Pharmacol Ther, 2001 Dec, 24(6), 423 - 31
Effects of altered plasma alpha-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysis; Kuroha M et al.; Effects of altered plasma alpha-1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis . Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions . Binding parameters were obtained from an in vitro study using ultrafiltration . Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs . Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased . Plasma concentration-time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated . All of the total plasma concentration-time profiles were different from those at normal AGP level . The differences were characterized by a higher initial concentration with faster or similar elimination . Unbound plasma concentration-time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level . These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required.

J Vet Pharmacol Ther, 2001 Dec, 24(6), 385 - 90
An assessment of antimicrobial consumption in food producing animals in Kenya; Mitema ES et al.; Antimicrobial agents are useful for control of bacterial infections in food animals and man . Their prudent use in these animals is important to control any possible development and transfer of resistance between animals and man . The objective of this study was to generate quantitative information to evaluate antimicrobial usage patterns by animal species, route of administration, antimicrobial class and type of use from 1995 to 1999 in Kenya . Theses data are essential for risk analysis and planning and can be helpful in interpreting resistance surveillance data, and evaluating the effectiveness of prudent use efforts and antimicrobial resistance mitigation strategies . Data on quantities of active substance classes were collected from the official records of the Pharmacy and Poisons Board of the Ministry of Health and analysed in MS Excel 2000 program . The mean antimicrobial consumption for the 5-year period was 14 594 +/- 1457 kg per year . This was distributed in the various antimicrobial classes as follows: 7975 kg (54.65%) of tetracyclines, 3103.96 kg (21.27%) of sulfonamides and 954.5 kg (6.56%) of aminoglycosides, 905 kg (6.20%) of beta-lactams, 94 kg (0.64%) of quinolones, 35 kg (0.24%) of macrolides and 24 kg (0.16%) of others (tiamulin) . Mean consumption per year among the various food animals was: 10 989 +/- 357 kg in large animals (cattle, sheep, pigs and goats), 2906 +/- 127 kg in poultry alone and 699 +/- 427 kg in both large animals and poultry . These quantities represented 56.56% (8255 kg) consumption per year for parenteral use, 41.79% (6098 kg) for oral use and 1.65% (241 kg) for topical use (intramammary and eye ointments) in cattle . With respect to intended use in food producing animals, the mean consumption per year was: 13 178 kg (90.30%) for therapeutic use (ST), 4 kg (0.03%) for prophylactic treatment (PT) and 1411 +/- 246 kg (9.67%) was used both for therapeutic and prophylactic purposes (GPT) . The study confirmed that antimicrobials are not used for growth promotion in Kenya . There was no specific trend in the quantities of active antimicrobial classes . This study has revealed that the tetracyclines, sulfonamides and trimethoprim, nitrofurans aminoglycosides, beta-lactams and the quinolones are the most commonly used drugs in food-producing animals in Kenya . Tetracyclines contributed approximately 55% of the total consumption, and there was an increasing trend in the consumption of quinolones from 1998.

J Am Chem Soc, 2002 Mar 27, 124(12), 2951 - 6
Total synthesis of (-)-tetrazomine . Determination of the stereochemistry of tetrazomine and the synthesis and biological activity of tetrazomine analogues; Scott JD et al.; The first total synthesis of the potent antitumor antibiotic (-)-tetrazomine has been accomplished . A new method for the formation of the allylic amine precursor to an azomethine ylide has been developed and exploited in an efficient {1,3}-dipolar cycloaddition to afford the key tetracyclic intermediate used in the synthesis of (-)-tetrazomine . Several analogues of tetrazomine have been synthesized and tested for antimicrobial and biochemical activity.

Farmaco, 2002 Jan, 57(1), 79 - 87
Synthesis and antimycobacterial activity of 3-aryl-, 3-cyclohexyl- and 3-heteroaryl- substituted-2-(1H(2H)-benzotriazol-1(2)-yl)prop-2-enenitriles, prop-2-enamides and propenoic acids . II; Sanna P et al.; A series of 32 3-aryl-, 3-cyclohexyl-, and 3-heteroaryl-substituted-2-(1H(2H)-benzotriazol-1(2)-yl)-prop-2-enenitriles, prop-2-enamides and propenoic acids, was synthesized as a part of our research in the antitubercular field, according to an international program with the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) . This work reports the preparation and analytical and spectroscopic characterization (MS, UV, IR, 1H NMR) of all compounds synthesized . Among these only a few compounds (E-4b,c, E-5a, E-7e and E-8d) were found to be endowed with modest growth inhibition of Mycobacterium tuberculosis . However, the obtained results allowed to acquire interesting structure-activity relationships.

Farmaco, 2002 Jan, 57(1), 39 - 44
Antimicrobial activity of 5-arylidene aromatic derivatives of hydantoin . Part 2; Szymanska E et al.; Various 5-chloroarylidene-2-amino substituted derivatives of imidazoline-4-one were synthesized and evaluated for their activity in vitro against Mycobacterium tuberculosis and other type strains of bacteria and fungi . 2-Chloro- and 2,4-dichlorobenzylidene substituted hydantoins exhibited antimycobacterial effect . The most potent compounds 3i, 3j, 3o, 3q and 3s were classified for further tests . The antimitotic effect of the investigated hydantoins was also examined.

Expert Rev Mol Diagn, 2001 May, 1(1), 30 - 8
DNA array technology and diagnostic microbiology; Anthony RM et al.; Near instantaneous detection of pathogens from clinical material, combined with simultaneous prediction of their antimicrobial resistance profiles, would revolutionize the impact of microbiology on the management of infection . Array-based assays allow a range of characteristics to be rapidly and simultaneously determined . At present these systems have found their primary role as research tools for the monitoring of mRNA expression in the form of DNA microarrays or 'chips' . As fabrication costs reduce and validated targeted arrays are developed, it is inevitable they will be used for more routine applications . Microfluidics offers the exciting possibility of combining purification, amplification and detection in a single disposable device; microarrays are particularly suitable for use within these systems . Arrays will become an important tool for clinical diagnostics.

J Wound Care, 2002 Feb, 11(2), 53 - 5
Why do some cavity wounds treated with honey or sugar paste heal without scarring?
Topham J.
As well as having antimicrobial properties, honey and sugar paste are associated with scarless healing in some cavity wounds . This article uses evidence to suggest why these products can modify excessive collagen production to prevent scarring.

J Trauma, 2002 Mar, 52(3), 463 - 8
Blood culturing practices in a trauma intensive care unit: does concurrent antibiotic use make a difference?
Schermer CR, Sanchez DP, Qualls CR, Demarest GB, Albrecht RM, Fry DE.
BACKGROUND: Febrile trauma patients have repeated blood cultures drawn during a prolonged hospitalization . We examined the diagnostic yield of blood cultures in severely injured patients to determine whether concurrent antimicrobial therapy or prophylactic administration of antibiotics affects blood culture growth . We also determined how rapidly growth changed to determine whether total numbers of blood cultures could be decreased . The hypotheses of the study were that concurrent antimicrobial administration affects blood culture yield, prophylactic administration alters the culture result, and repetitive culturing is unnecessary . METHODS: A retrospective chart review of trauma patients with minimum Injury Severity Score of 15 and minimum 5-day intensive care unit length of stay was performed . The dates and results of blood cultures and antibiotic type and administration dates were recorded . "Prophylactic" antibiotics were defined as antibiotics administered on admission to the unit . Computer software was used to match the blood culture date to the period of antimicrobial administration . Categorical data were compared using Fisher's exact test . RESULTS: Two hundred fifty-eight patients met entry criteria, and 208 charts were complete for review . One hundred twenty-nine patients had 347 sets of blood cultures drawn . The positive blood culture rate was 10.8% in patients off antibiotics, and 13.9% in patients on antibiotics (p = 0.68) . All prophylactic antibiotics included a beta-lactam . Only 18% of positive blood cultures in patients receiving prophylactic antibiotics were sensitive to beta-lactams as opposed to 59% sensitivity in those who did not receive prophylaxis (p = 0.03) . One hundred seventy-six sets of blood cultures were performed after an initial positive culture . Only three patients with an initial positive culture had a second positive culture with a different organism . The mean time to culturing a new organism after initial growth was 19 days . CONCLUSION: Concurrent antimicrobial administration does not alter blood culture yield . Prophylactic administration alters the type of organism cultured . Little new information is gained from repetitive culturing.

Eur J Med Chem, 2002 Mar, 37(3), 197 - 206
Synthesis, characterisation and biological activity of novel 4-thiazolidinones, 1,3,4-oxadiazoles and some related compounds; Kucukguzel SG et al.; Two novel series of 4-thiazolidinone derivatives, namely 2-substituted-3-({4-(4-methoxybenzoylamino)benzoyl}amino)-4-thiazolidinones (7a-e) and 2-{4-(4-methoxybenzoylamino)benzoylhydrazono}-3-alkyl-4-thiazolidinones (5a-c) together with 2-{4-(4-methoxybenzoylamino)phenyl}-5-(substituted phenyl)amino-1,3,4-oxadiazoles (6a-c) have been synthesised as title compounds . N(1)-{4-(4-methoxybenzoylamino)benzoyl}-N(2)-substituted methylene hydrazines (3a-e) and 1-{4-(4-methoxybenzoylamino)benzoyl}-4-substituted phenyl thiosemicarbazides (4a-f) were also prepared and used as intermediate to give the title compounds . All synthesised compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv and antimicrobial activities against various bacteria and fungi . Compounds 7a and 7b were found as the most active derivatives demonstrating 90 and 98% inhibition of mycobacterial growth of M . tuberculosis H37Rv in the primary screen at 6.25 microg mL(-1), respectively . However, level II assay revealed that the MIC values were not less than 6.25 microg mL(-1) . None of the compounds showed significant antimicrobial activity against the microorganisms used whereas 3a and 7a inhibited the growth of several bacteria and fungi.

Biochemistry, 2002 Mar 26, 41(12), 4096 - 106
Role of the oxyanion binding site and subsites S1 and S2 in the catalysis of oligopeptidase B, a novel target for antimicrobial chemotherapy; Juhasz T et al.; Oligopeptidase B is a member of a novel serine peptidase family, found in Gram-negative bacteria and trypanosomes . The enzyme is involved in host cell invasion, and thus, it is an important target for drug design . Oligopeptidase B is specific for substrates with a pair of basic residues at positions P1 and P2 . The sensitivity of substrates to high ionic strength suggests that the arginines interact with the carboxylate ions of the enzyme . On the basis of a three-dimensional model, two carboxyl dyads (Asp460 and Asp462 and Glu576 and Glu578) can be assigned as binding sites for arginines P1 and P2, respectively . The dyads are involved in several events: (i) substrate binding, (ii) substrate inhibition at high substrate concentrations (different inhibitory mechanisms were demonstrated with substrates bearing one and two arginine residues), (iii) enzyme activation at millimolar CaCl2 concentrations with substrates having one arginine, and (iv) interaction of Ca2+ with the dyads which simplified the complex pH dependence curves . Titration with a product-like inhibitor revealed the pK(a) of the carboxyl group that perturbed the pH-kcat/Km profiles . The OH group of Tyr452 is part of the oxyanion binding site, which stabilizes the transition state of the reaction . Its role studied with the Tyr452Phe variant indicates that (i) the catalytic contribution of the OH group depends on the substrate and (ii) the catalysis is, unusually, an entropy-driven process at physiological temperature . The NH group of the scissile peptide bond accounts for the deviation of the reaction from the Eyring plot above 25 degrees C, and for abolishing potential nonproductive binding.

Pol Merkuriusz Lek, 2001 Dec, 11(66), 491 - 4
{The relation between Chlamydia pneumoniae infection and abdominal aortic aneurysm}; Wolski A et al.; The aim of our study was to evaluate the frequency of C . pneumoniae infection in abdominal aortic aneurysm (AAA) patients by measuring C . pneumoniae specific serum IgG, IgM and IgA levels and the activation of their immune system by measuring the concentrations of IL-10, IL-12, IFN-gamma and TNF-alpha in patients' serum . Microimmunofluorescence method was applied to evaluate the level of anti-C . pneumoniae IgG, IgA and IgM . The concentrations of cytokines were evaluated using ELISA method . Serologic markers of persistent C . pneumoniae infection have been detected in 25/28 (89.3%) patients and in 6/20 (30%) healthy controls . In 40% (10/25) of patients with serologic markers of persistent C . pneumoniae infection high titers of specific IgG and IgA indicated active infection--reinfection or exacerbation of chronic infection . Mean concentrations of IL-10, IL-12, IFN-gamma and TNF-alpha indicated lack of protection against intracellular pathogens . Since all patients in this group were diagnosed as having symptomatic AAA, we suggest that active infection can exacerbate inflammation in the AAA wall and accelerate progression of the disease . In our opinion patients with active C . pneumoniae infection may be candidates to the antimicrobial treatment.

Curr Mol Med, 2001 Mar, 1(1), 137 - 51
Natural T cell immunity to intracellular pathogens and nonpeptidic immunoregulatory drugs; Poccia F et al.; Natural T (NT) lymphocytes recognize infected cells or microbial compounds without the classical genetic restriction of polymorphic major histocompatibility complex (MHC) molecules . This innate recognition pathway results in a broad and rapid antimicrobial response that may be critical for controlling the spread of intracellular pathogens, requiring the elimination of the infecting agent from both extracellular spaces and host cells . NT cells are mainly composed of alphabeta and gammadelta T lymphocytes that express natural killer (NK) receptors and recognize preferentially various nonpeptidic antigens . Similar to NK cells, NT lymphocytes can 'see' and kill target cells deficient in the expression of one or more MHC class I molecules . NT cells expressing the alphabeta TCR can recognize lipid and lipoglycan antigens presented in the context of nonpolymorphic CD1 molecules, whereas phosphocarbohydrates and akilamines induce constitutive responses in most Vgamma9Vdelta2 NT lymphocytes . The remaining fraction of gammadelta NT cells express the Vdelta1 chain associated with different Vgamma-chains and may directly recognize self-antigens such as MICA, MICB or CD1 molecules . It is possible that NT lymphocytes may play two opposite roles during intracellular infections . First, in the acute phase, they may be critical for the initiation of pathogen elimination . Second, in the chronic phase, NT cells may be dangerous, if their potential autoreactivity is not well controlled . It is conceivable that novel strategies of immune intervention against emerging and re-emerging intracellular pathogens, such as human immundeficiency virus (HIV), hepatitis-C virus (HCV) and Mycobacterium tuberculosis (MTB) may involve the control of NT cell activation/anergy by (nonpeptidic) immunoregulatory drugs.

Pharmacotherapy, 2002 Mar, 22(3 Pt 2), 71S - 79S
The rationale for aerosolized antibiotics; Flume P et al.; In order for an antimicrobial agent to be effective, it must fulfill two requirements . First, the agent must reach the site of infection and remain in the vicinity for an adequate length of time . Second, it must bind to a target site and remain bound for a length of time sufficient to disrupt the life cycle of the cell . Once these requirements are met, the drug is able to exert its antimicrobial activity against the cell . In an effort to better understand and predict the killing activity of antibiotics, we have attempted to develop parameters that describe the accumulation and diffusion of drug to and from body sites (pharmacokinetics) and quantify how much of a compound is needed at the site of infection to yield the desired effect (minimum inhibitory concentration) . Furthermore, integration of these parameters allows us to evaluate host, drug, and microbial factors and formulate criteria to assess and predict drug activity in patients (pharmacodynamics) . Knowledge and application of pharmacodynamic principles can assist clinicians in optimizing antimicrobial therapy by allowing them to maximize the antimicrobial activity of an agent while minimizing patient exposure and thus reducing the likelihood of toxicity.

Antimicrob Agents Chemother, 2002 Apr, 46(4), 1141 - 3
In vitro activities of a new des-fluoroquinolone, BMS 284756, and seven other antimicrobial agents against 151 isolates of Eikenella corrodens; Goldstein EJ et al.; The des-fluoroquinolone BMS 284756 was active in vitro against all 151 clinical strains of Eikenella corrodens at a MIC of < or = 0.25 microg/ml and was comparable in activity to moxifloxacin and levofloxacin . The MIC at which 90% of the isolates were inhibited by penicillin G was 2 microg/ml; MICs for 8.6% of the strains (13 of 151) were > or = 4 microg/ml, including for two beta-lactamase-producing isolates . Amoxicillin-clavulanate and ampicillin-sulbactam inhibited all strains at a MIC of < or = 1 microg/ml.

Antimicrob Agents Chemother, 2002 Apr, 46(4), 1114 - 6
Susceptibilities of Mycobacterium marinum to gatifloxacin, gemifloxacin, levofloxacin, linezolid, moxifloxacin, telithromycin, and quinupristin-dalfopristin (Synercid) compared to its susceptibilities to reference macrolides and quinolones; Braback M et al.; The susceptibility pattern of Mycobacterium marinum was determined . Quinupristin-dalfopristin and telithromycin were less active than clarithromycin . Linezolid showed good antimicrobial activity at clinically achievable concentrations . Gatifloxacin, levofloxacin, and moxifloxacin displayed activities similar to those of ciprofloxacin . Gemifloxacin was less active . The Etest method showed variable agreement with the reference method.

Antimicrob Agents Chemother, 2002 Apr, 46(4), 1032 - 7
Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp . and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000; Pfaller MA et al.; Posaconazole, ravuconazole, and voriconazole are new triazole derivatives that possess potent, broad-spectrum antifungal activity . We evaluated the in vitro activity of these investigational triazoles compared with that of itraconazole and amphotericin B against 239 clinical isolates of filamentous fungi from the SENTRY Program, including Aspergillus spp . (198 isolates), Fusarium spp . (7 isolates), Penicillium spp . (19 isolates), Rhizopus spp . (4 isolates), Mucor spp . (2 isolates), and miscellaneous species (9 isolates) . The isolates were obtained from 16 different medical centers in the United States and Canada between January and December 2000 . In vitro susceptibility testing was performed using the microdilution broth method outlined in the National Committee for Clinical Laboratory Standards M38-P document . Overall, posaconazole was the most active compound, inhibiting 94% of isolates at a MIC of < or = 1 microg/ml, followed by voriconazole (91%), amphotericin B (89%), ravuconazole (88%), and itraconazole (70%) . All three new triazoles demonstrated excellent activity (MIC, < or = 1 microg/ml) against Aspergillus spp . (114 Aspergillus fumigatus, 22 Aspergillus niger, 13 Aspergillus flavus, 9 Aspergillus versicolor, 8 Aspergillus terreus, and 32 Aspergillus spp.): posaconazole (98%), voriconazole (98%), ravuconazole (92%), amphotericin B (89%), and itraconazole (72%) . None of the triazoles were active against Fusarium spp . (MIC at which 50% of the isolates tested were inhibited {MIC(50)}, >8 microg/ml) or Mucor spp . (MIC(50), >8 microg/ml) . Posaconazole and ravuconazole were more active than voriconazole against Rhizopus spp . (MIC(50), 1 to 2 microg/ml versus >8 microg/ml, respectively) . Based on these results, all three new triazoles exhibited promising activity against Aspergillus spp . and other less commonly encountered isolates of filamentous fungi . The clinical value of these in vitro data remains to be seen, and in vitro-in vivo correlation is needed for both new and established antifungal agents . Surveillance efforts should be expanded in order to monitor the spectrum of filamentous fungal pathogens and their in vitro susceptibility as these new antifungal agents are introduced into clinical use.

Antimicrob Agents Chemother, 2002 Apr, 46(4), 943 - 6
Development of a whole-cell assay for peptidoglycan biosynthesis inhibitors; Barbosa MD et al.; Osmotically stabilized Escherichia coli cells subjected to freezing and thawing were utilized as the source of enzymes for a peptidoglycan pathway assay that can be used to simultaneously test all targets of the committed steps of cell wall biosynthesis . The use of (14)C-labeled UDP-N-acetylglucosamine (UDP-GlcNAc) as a substrate allows the direct detection of cross-linked peptidoglycan formed . The assay was validated with known antibiotics . Fosfomycin was the strongest inhibitor of the pathway assay, with a 50% inhibitory concentration of 1 microM . Flavomycin, bacitracin, vancomycin, D-cycloserine, penicillin G, and ampicillin also inhibited formation of radiolabeled peptidoglycan by the E . coli cells . Screening of compounds identified two inhibitors of the pathway, Cpd1 and Cpd2 . Subsequent tests with a biochemical assay utilizing purified enzyme implicated UDP-GlcNAc enolpyruvyl transferase (MurA) as the target of Cpd1 . This compound inhibits the first enzyme of the pathway in a time-dependent manner . Moreover, enzyme inactivation is dependent on preincubation in the presence of UDP-GlcNAc, which forms a complex with MurA, exposing its active site . Cpd1 also displayed antimicrobial activity against a panel of microorganisms . The pathway assay used in conjunction with assays for individual enzymes provides an efficient means of detecting and characterizing novel antimicrobial agents.

J Heart Lung Transplant, 2002 Mar, 21(3), 354 - 9
Nocardia infection in lung transplant recipients; Husain S et al.; BACKGROUND: Nocardia is responsible for infection in both normal and immunocompromised hosts . Organ transplant recipients are increasingly recognized as a sub-group of immunocompromised patients in whom nocardia is an important pathogen . The frequency of nocardia in organ transplant recipients varies between 0.7% and 3% . Nocardia infection has largely been reported in heart, kidney and liver transplant recipients . Presentations of nocardia in lung transplant recipients have been restricted primarily to case reports . The present study reviews the clinical and epidemiologic characteristics of nocardia infection in lung transplant recipients at our institution . METHODS: A retrospective cohort study of 473 lung transplant recipients from January 1991 to November 2000 was done at a university hospital . Patient demographics, immunosuppressive regimen at the time of isolation of nocardia species, use of trimethoprim-sulfamethoxazole for Pneumocystis carinii prophylaxis, rejection episodes in the preceding 6 months, concurrent pathogens, site of infection, radiologic findings and treatment and outcome were recorded . RESULTS: Nocardia infection was found in 2.1% (10 of 473) of our lung transplant recipients . Median time of onset was 34.1 months after transplantation . Nocardia species included N farcinica in 30% (3 of 10), N nova in 30% (3 of 10), N asteroides complex in 30% (3 of 10) and N brasiliensis in 10% (1 of 10) of patients . Post-transplant diabetes was present in 50% (5 of 10) of patients . The primary indication for lung transplantation was emphysema in 40% (4 of 10) . Native lung involvement was noted in 75% (3 of 4) of patients with single lung transplant . Breakthrough nocardia infection were noted in 6 patients who were receiving trimethoprim-sulfamethoxazole prophylaxis for P carinii pneumonia; all breakthrough isolates remained susceptible to trimethoprim-sulfamethoxazole . Overall mortality was 40% (4 of 10) . All patients (3 of 3) with infection due to N farcinica, except 1 (1 of 7) with infection due to other nocardia species, died . Seventy-five percent (3 of 4) of deaths were attributable to nocardia infection . CONCLUSIONS: Nocardia infection tended to involve the native lung in single lung transplant recipients . Trimethoprim-sulfamethoxazole for P carinii prophylaxis at the doses given was not protective against nocardiosis in these patients . Infection with N farcinica was associated with poor outcome . Thus, species identification and extended courses of antibiotics based on antimicrobial susceptibility testing are important in management of these patients.

Infect Immun, 2002 Apr, 70(4), 1860 - 6
Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binding ability of interleukin-8 in human endothelial cells; Elass E et al.; Interleukin-8 (IL-8), a C-X-C chemokine bound to endothelium proteoglycans, initiates the activation and selective recruitment of leukocytes at inflammatory foci . We demonstrate that human lactoferrin, an antimicrobial lipopolysaccharide (LPS)-binding protein, decreases both IL-8 mRNA and protein expression induced by the complex Escherichia coli 055:B5 LPS/sCD14 in human umbilical vein endothelial cells . The use of recombinant lactoferrins mutated in the LPS-binding sites indicates that this inhibitory effect is mediated by an interaction of lactoferrin with LPS and CD14s that suppresses the endotoxin biological activity . Furthermore, since dimeric IL-8 and lactoferrin are both proteoglycan-binding molecules, the competition between these proteins for heparin binding was investigated . Lactoferrin strongly inhibited the interaction of radiolabeled IL-8 to immobilized heparin, whereas a lactoferrin variant lacking the amino acid residues essential for heparin binding was not inhibitory . Moreover, this process is specific, since serum transferrin, a glycoprotein whose structure is close to that of lactoferrin, did not prevent the interaction of IL-8 with heparin . These results suggest that the anti-inflammatory properties of lactoferrin during septicemia are related, at least in part, to the regulation of IL-8 production and also to the ability of lactoferrin to compete with chemokines for their binding to proteoglycans.

Curr Allergy Asthma Rep, 2002 Jan, 2(1), 16 - 25
Allergic adverse reactions to sulfonamides; Choquet-Kastylevsky G et al.; Antimicrobial sulfonamides were the first antimicrobial agents used effectively to treat infectious diseases . However, because they may cause severe adverse drug reactions (ADRs) and because more effective agents have since been developed, sulfonamides now are used for only a few indications in specific groups, such as AIDS patients . Skin reactions, from benign rash to potentially lethal toxidermias, are the most frequent ADRs to sulfonamides . Other major ADRs include acute liver injury, pulmonary reactions, and blood dyscrasias . Although the mechanisms involved have not been fully elucidated, reactive metabolites appear to play a pivotal role . The hydroxylamine and nitroso metabolites of sulfamethoxazole, the most frequently used sulfonamide today, can bind covalently to proteins because of their chemical reactivity, resulting in the induction of specific adverse immune responses . Therefore, changes in the activity of metabolic and detoxification pathways are associated with a greater risk for developing allergic reactions to sulfonamides . Allergies to sulfonamides, particularly sulfamethoxazole (often used in combination with trimethoprim as co-trimoxazole), are more frequent in AIDS patients, but the reason for this increased risk is not fully understood . No valid tools are available to predict which patients have a greater risk for developing allergies to sulfonamides . Diagnosis is essential to avoid a possible evolution toward severe reactions and readministration of the offending drug . In patients who absolutely require further treatment, successful desensitization may be achieved.

J Clin Periodontol, 2002 Feb, 29(2), 87 - 91
The effects of subgingival calculus on the clinical outcomes of locally-delivered controlled-release doxycycline compared to scaling and root planing; Johnson LR et al.; BACKGROUND, AIM: The effect of subgingival calculus on the clinical outcomes of the local delivery of antimicrobials is unknown . This study examines the clinical outcomes of treatment with locally delivered controlled-release doxycycline (DH) or scaling and root planing (SRP) in subsets of adult periodontitis patients with known baseline levels of subgingival calculus . METHODS: The data examined were obtained from 393 patients who participated in 2 multi-center trials . All patients had baseline subgingival calculus levels assessed and were then treated at baseline and month 4 with either DH or SRP . Clinical attachment levels (CAL), pocket depth (PD) and bleeding on probing (BOP) were assessed at baseline and months 1, 2, 4, 5, 6, 8 and 9 . RESULTS: Treatment with either DH or SRP resulted in significant statistical and clinical improvements in CAL, PD and BOP . These clinical outcomes were equivalent regardless of the extent of subgingival calculus present at baseline . CONCLUSIONS: The results indicate that the primary clinical effects of these therapies are the result of a disruption and reduction of the subgingival plaque and not the effect of the removal of subgingival calculus and contaminated cementum.

Int J Dermatol, 2002 Jan, 41(1), 28 - 31
Scrofuloderma and Sweet's syndrome; Mahaisavariya P et al.; BACKGROUND: In recent years, the rare association of Sweet's syndrome with nontuberculous mycobacterial lymphadenitis has been reported . OBJECTIVE: To report the clinical, demographic, and bacteriologic data and association with Sweet's syndrome of 18 patients with scrofuloderma and scrofuloderma-like condition caused by nontuberculous mycobacterial infections seen during the past 7 years (1994-2000) . METHODS: In all patients, a biopsy specimen was obtained for histopathologic and microbiologic studies . Patients from whom Mycobacterium tuberculosis and nontuberculous mycobacteria were isolated from the culture of skin biopsy specimens were included . Deep fungal infection was excluded by the lack of a fungal element in histologic section and cultural methods . The patients were treated with antimicrobials or antituberculous drugs according to the causative species . RESULTS: Eighteen cases of scrofuloderma (nine male, nine female; mean age, 36.9 years) were found among 104 patients with cutaneous tuberculosis and nontuberculous mycobacterial cutaneous infections . Sixteen of the 18 cases had lymphadenitis as the underlying focus of scrofuloderma: 15 cases occurred in the cervical group and one case in the inguinal area . One case drained from the soft tissue and one from the paranasal air sinus . Five cases had multiple episodes of Sweet' s syndrome during the course of treatment . Most cases in this group (four of the five) were middle-aged women with cervical lymphadenitis, and the most common species were rapid growers . CONCLUSIONS: Age, sex, and the site of infection may have some influence on the association with Sweet's syndrome in nontuberculous mycobacterial infections.

Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi, 2002, 12(2), 105 - 19
{Study on the detection methods of Helicobacter pylori from clinical specimens}; Murata Y et al.; We have attempted the detection of Helicobacter pylori using biopsy specimen (tunica mucosa vestibulum ventriculi, tunica mucosa corpus ventriculi) and of Helicobacter pylori Specific Antigen (HpSA) from feces of patients with stomach-duodenum disease . During 1991-2000, 753 patients had biopsy test for Gram-stained smear, culture, rapid urease test (RUT), and HpSA by ELISA . As a result, Gram stained smear positive were 609 (44.6%) in 1,357 specimens, culture positive were 984 (72.5%) in 1,357 specimens, and RUT positive were 445 (59.4%) in 749 specimens in method with stomach specimens . 85 (94.4%) in 90 specimens with method of HpSA were positive, and we defined that indirect detection method using feces was most significance compared with other invasive direct method using endoscopy . In addition, antimicrobial susceptibility tests were examined with 5 agents for 349 strains of H . pylori, the MICs of amoxicillin were <0.01-0.19 microgram/ml (MIC80: 0.02 microgram/ml), and clarithromicin were <0.01-50 microgram/ml (MIC80: 0.04 microgram/ml) . Amoxicillin resistant strain was not observed.

J Periodontol, 2002 Feb, 73(2), 167 - 72
Comparison of conventional periodontal maintenance versus scaling and root planing with subgingival minocycline; Meinberg TA et al.; BACKGROUND: Alternative regimens using subgingival antimicrobials compared to conventional periodontal maintenance (PM) may lead to more efficient protocols . The purpose of this study was to evaluate treatment time and clinical and radiographic outcomes in 2 periodontitis cohorts, one receiving conventional PM and the other receiving scaling and root planing (SRP) and multiple doses of subgingival minocycline . METHODS: Moderate to advanced chronic periodontitis patients were concurrently treated with either: 1) scaling and root planing and 4 subgingival doses of minocycline microspheres in all > or = 5 mm pockets over a 6-month period (RP/M; n = 24 patients); or 2) conventional 3-month periodontal maintenance (PM; n = 24 patients) . Clinical and radiographic measurements, including probing depth (PD), clinical attachment level (CAL), and interproximal bone height (BH), were analyzed in 2 premolar/molar interproximal > or = 5 mm pockets at baseline and 1 year using paired t tests, analysis of variance, chi-square analysis, and correlation coefficients . RESULTS: Baseline clinical and radiographic data were similar between RP/M and PM patients . Probing depths showed greater mean improvement in RP/M (0.9 +/- 0.1 versus 0.4 +/- 0.1 mm, P = 0.02), with 25% of subjects in RP/M gaining > or = 2 mm compared to 4.2% in PM (differences were statistically significant) . The mean loss in bone height and percent subjects losing bone height were less in RP/M (0.05 +/- 0.05 mm; 12.5%) than PM (0.09 +/- 0.08 mm; 16.7%), but bone height differences were not statistically significant . A subset of RP/M molar furcation sites responded with similar PD reduction and no BH loss over 1 year . While cross-sectional RP/M data between CAL and BH, or PD and CAL were highly correlated, changes over 1 year were not correlated among any of these parameters . CONCLUSIONS: Scaling and root planing and subgingival minocycline in experimental sites took little time (<5 minutes/appointment), but resulted in more probing depth reduction and less frequent bone height loss than conventional periodontal maintenance.

Epidemiol Infect, 2002 Feb, 128(1), 21 - 7
Non-invasive pneumococcal disease and antimicrobial resistance: vaccine implications; Kyaw MH et al.; We reviewed laboratory data on non-invasive pneumococcal isolates reported from all diagnostic laboratories in Scotland during the period 1988-99 . Of 4491 isolates from hospitalized patients, 654 (64.7%) were from sputum, 79 (7.8%) from the nasopharynx and 278 (27.5%) from other superficial sites . The serogroups included in the 23-valent polysaccharide vaccine caused 96.9% of all non-invasive disease in all age groups . The 7-, 9-, and 11-valent conjugated vaccine serogroups were responsible for 87-94%, 85-93%, 74-81% and 75-84% of non-invasive disease respectively in age groups < 2 years, < or = 5 years, > or = 65 years and all ages . The coverage of non-susceptible penicillin and erythromycin non-invasive isolates was > 99% and > 95% with the 23-valent polysaccharide and 7-11-valent conjugate vaccines respectively . The eight most common serogroups were 23, 9, 6, 19, 14, 3, 15 and 11 (in descending order) . The serogroups associated with antimicrobial resistance in non-invasive disease were similar to those found in invasive disease . The finding of a similar serogroup distribution in both invasive and non-invasive disease (regardless of the site of clinical isolate), is consistent with serogroups colonizing non-sterile sites and having the potential to invade . The availability of conjugated vaccines reinforces the importance of systematic surveillance to determine accurately and regularly the coverage of pneumococcal serogroups and types causing both invasive and non-invasive disease.

Ann Pharmacother, 2002 Mar, 36(3), 530 - 2
Pharmacodynamics in the evaluation of drug regimens; Bhavnani SM et al.; We believe, especially in an era of increasing antimicrobial resistance, that the integration of PK/PD models and stochastic techniques provides a powerful new tool to clinicians, researchers, and regulatory agencies alike . By using techniques such as these, we can begin to level the playing field so that PK/PD measures for therapeutic agents can be more accurately compared with greater certainty, and not be limited to discussions of susceptibility method variation or comparisons of MIC results.

Am J Med, 2002 Feb 15, 112(3), 204 - 11
Antimicrobial therapy of gram-negative bacteremia at two university-affiliated medical centers; Graff LR et al.; PURPOSE: To describe antimicrobial prescribing practices and patient outcomes associated with the treatment of aerobic gram-negative rod bacteremia at two university-affiliated medical centers . SUBJECTS AND METHODS: All adult patients with gram-negative bacteremia (N = 326) who were at Stanford and University of California, San Francisco (UCSF) Hospitals from September 1, 1996 through August 31, 1997 were evaluated via retrospective review of medical records . RESULTS: Most patient characteristics were similar between institutions; however, patients at Stanford were more likely to have had a diagnosis of bone marrow transplantation, liver failure, or poor nutritional status, while more patients at UCSF had solid organ transplant, diabetes, pulmonary disease, or hypotension . The bacteriology was similar at both sites, with Escherichia coli the predominant pathogen (139 {43%} of 326) . The majority of episodes were community acquired (67% {218/326}) . Patients at Stanford were more likely to have been treated empirically with aminoglycosides (28% vs . 7%, P <0.001) and noncephalosporin beta-lactams (31% vs . 11%, P <0.001), while patients at UCSF were more likely to have received cephalosporins (62% vs . 29%, P <0.001) and fluoroquinolones (21% vs . 11%, P = 0.02) . These patterns continued for definitive therapy . Overall mortality was 60 (19%) of 326 . Several risk factors were associated with 14-day mortality, including severity of illness, neutropenia, diabetes mellitus, use of vasopressors, and empiric use of a noncephalosporin beta-lactam . CONCLUSION: Prescribing practices for the treatment of gram-negative bacteremia differed significantly in the two institutions despite similar patients and pathogens.

Curr Opin Investig Drugs, 2001 Dec, 2(12), 1681 - 90
Combinatorial biosynthesis in microorganisms as a route to new antimicrobial, antitumor and neuroregenerative drugs; Hutchinson CR et al.; Combinatorial biosynthesis utilizes the genes of biosynthetic pathways that produce microbial products to create novel chemical structures . The engineering of mondular polyketide synthase (PKS) genes has been the major focus of this effort and has led to the production of analogs of macrolide antibiotics like the erythromycins and their derived ketolides, and of the immunosuppressive macrolide FK-520 (Fujisawa Pharmaceutical Co Ltd) . Approaches to making analogs of the promising antitumor compounds known as epothilones are also being explored . Lead compounds for further study have resulted and routes to analogs of other pharmacologically important compounds have been established . To facilitate this work, many new tools for manipulating and studying the multifunctional PKSs have been developed including the development of Escherichia coli as a PKS expression last . These developments have resulted in faster ways of engineering PKS to produce new compounds for the development of chemotherapeutic agents from natural products.

J Chemother, 2002 Feb, 14(1), 47 - 53
Experimental studies on synergism between aminoglycosides and the antimicrobial antiinflammatory agent diclofenac sodium; Annadurai S et al.; The antiinflammatory agent diclofenac sodium (Dc) exhibited remarkable antibacterial effects both in vitro and in vivo . Fifteen different bacteria sensitive to Dc as well as to a number of common antibiotics were tested for synergistic effects in vitro . Disc diffusion test with Dc and aminoglycosides assessed by stringent computation showed clear-cut synergism . Synergism between Dc and streptomycin (Sm) was found to be statistically significant (p < or = 0.01) when compared with their individual effects . By the checkerboard assessment procedure, the fractional inhibitory concentration (FIC) index of this combination was found to be 0.49, confirming synergism . The mouse protective capacity of this combination was then evaluated in vivo against S . typhimurium as the virulent infecting bacterium, and the size of bacterial load determined from infected autopsied animals . Statistical analysis by Student's 't' test suggested this drug combination is highly synergistic; synergism was also noted between Dc and other aminoglycosides.

J Pept Res, 2001 Nov, 58(5), 433 - 41
Structure-function studies on the amphibian peptide brevinin 1E: translocating the cationic segment from the C-terminal end to a central position favors selective antibacterial activity; Kumari VK et al.; Brevinin 1E, which has the sequence FLPLLAGLAANFLPKIFCKITRKC, is an antimicrobial peptide isolated from the skin secretions of the European frog Rana esculenta . Both the linear and the disulfide-bridged forms have relatively broad-spectrum antibacterial as well as hemolytic activities . The antibacterial and hemolytic activities and biophysical properties of synthetic peptides corresponding to brevinin 1E and its analog in which the segment CKITRKC has been transposed to a central location resulting in the sequence FLPLLAGLCKITRKCAANFLPKIF have been investigated . Our studies indicate that the analog peptide has antibacterial activity comparable with brevinin 1E, but with considerably reduced hemolytic activity . The linear variant of the analog has no hemolytic activity, unlike the linear form of brevinin 1E . The biological activities can be explained on the basis of relative affinities for anionic and zwitterionic lipids . A cluster of cationic amino acids flanked on one side by a hydrophobic stretch of amino acids and another side composed of apolar amino acids appears to favor preferential antibacterial activity.

Curr Allergy Asthma Rep, 2001 Jul, 1(4), 364 - 72
Antibiotic theory in otitis media; Gungor A et al.; Otitis media is currently the most common diagnosis made by clinicians, which has a major impact on managed care . The emergence of resistant bacterial pathogens has caused controversy over the use of antibiotics when acute otitis media (AOM) is diagnosed . All infants with AOM and all older children with severe AOM should be treated with antibiotics, despite concerns about rising rates of resistant bacterial pathogens . Some older children with nonsevere AOM may be candidates for initial observation, although this is not confirmed by clinical trials . Antimicrobial agents are not required for otitis media with effusion of recent onset but may be considered if this effusion becomes chronic; in these cases, tympanostomy tube placement may be indicated . Antimicrobial prophylaxis for prevention of recurrent AOM should be reserved for selected patients because of the possible emergence of resistant organisms . Tympanostomy tube placement is a more reasonable option today.

Semin Respir Infect, 2002 Mar, 17(1), 65 - 71
Emergency department management of acute respiratory infections; Ward MA; Respiratory tract infections are one of the most common problems prompting visits to the emergency department . Although many are the result of self-limited viral illnesses, these infections may result in substantial morbidity and, rarely, mortality . Prompt recognition and appropriate treatment can reduce morbidity and largely prevent mortality . Careful selection of antimicrobial agents is essential to maximize benefit and prevent overuse, which contributes to the emergence of antibiotic resistance.

Am J Pathol, 2002 Mar, 160(3), 841 - 8
CAP37, a novel inflammatory mediator: its expression in endothelial cells and localization to atherosclerotic lesions; Lee TD et al.; Cationic antimicrobial protein of 37 kd (CAP37), originally isolated from human neutrophils, is an important multifunctional inflammatory mediator . Here we describe its localization within the vascular endothelium associated with atherosclerotic plaques . Evidence from in vitro immunocytochemical, Northern blot, and reverse transcriptase-polymerase chain reaction analysis indicates that CAP37 is induced in endothelial cells in response to inflammatory mediators . Endothelial-derived CAP37 shows sequence identity with an extensive region of neutrophil-derived CAP37 . This is the first demonstration of endogenous endothelial CAP37, confirmed by sequence analysis . We suggest that, because of its induction and location in the endothelium and its known monocyte- and endothelial-activating capabilities, CAP37 has potential to modulate monocyte/endothelial dynamics at the vessel wall in inflammation.

J Ethnopharmacol, 2002 Apr, 80(1), 25 - 35
Screening of African medicinal plants for antimicrobial and enzyme inhibitory activity; Tshibangu JN et al.; Seven plant species, belonging to different families, were collected in the eastern part of the Republic of Congo (Kivu) based on ethnopharmacological information . Their dichloromethane and methanolic extracts were tested for biological activity . Five of the seven collected plants exhibited antiplasmodial activity with IC(50) values ranging from 1.1 to 9.8 microg/ml . The methanolic extract of Cissampelos mucronata was the most active one showing activity against chloroquine sensitive (D6) and chloroquine resistant (W2) Plasmodium falciparum strains with IC(50) values of 1.5 and 1.1 microg/ml, respectively . Additionally, this extract significantly inhibited the enzyme tyrosine kinase p56(lck) (TK) . The dichloromethane extract of Amorphophallus bequaertii inhibited the growth of Mycobacterium tuberculosis with a MIC of 100 microg/ml and the methanolic extract of Rubus rigidus inhibited the activity of both enzymes HIV1-reverse transcriptase (HIV1-RT) and TK p56(lck).

J Altern Complement Med, 2002 Feb, 8(1), 77 - 83
Comparison of propolis skin cream to silver sulfadiazine: a naturopathic alternative to antibiotics in treatment of minor burns; Gregory SR et al.; BACKGROUND: Propolis, a naturopathic substance derived from bees wax extract, has recently been praised for its antimicrobial, anti-inflammatory, and cicatrization-enhancing properties . OBJECTIVE: In our study, we compare these properties in a high-grade Brazilian propolis skin cream directly with silver sulfadiazene (SSD) in the treatment of minor burns (superficial second degree) in the ambulatory care setting (less than 20% total body surface area burned) . SETTINGS/LOCATION: The study was conducted at the burn clinic in Pronto Socorro para Queimaduras, Gioania, Brazil . SUBJECT: Patients were admitted to the study only if their initial presentation for burn care was within 48 hours postinjury and if bilateral wounds of similar depth and quality were present . INTERVENTIONS: Patients had propolis skin cream applied to one wound and SSD applied to the other selected wound on initial presentation and underwent debridement and dressings change the following morning . Patients subsequently returned to the clinic every 3 days to have the wounds checked and dressings changed . At these check-ups, wounds were cultured for microbial growth and photographed to document inflammation and cicatrization . Patients were instructed not to disturb their wounds or change their dressings at home, thus propolis skin cream and SSD were applied to the wounds only at the specified 3-day intervals . RESULTS: Our preliminary results do not show any significant difference in microbial colonization between wounds treated with SSD and propolis skin cream, however, wounds treated with propolis skin cream consistently showed less inflammation and more rapid cicatrization then those treated with SSD . CONCLUSION: Propolis skin cream appears to have a beneficial effects on the healing of partial thickness burn wounds . If dressings had been changed more frequent the antimicrobial and wound healing effects would have been enhanced.

Int Surg, 2001 Jan-Mar, 86(1), 62 - 6
Descending necrotizing mediastinitis: a case report and review of the literature; Balkan ME et al.; Descending necrotizing mediastinitis (DNM) is a highly fatal disease and as infection spreads along deep cervical planes into the mediastinum, widespread cellulitis, necrosis, abscess formation, and sepsis may occur . Early diagnosis is crucial for starting aggressive treatment without delay . Cervicothoracic computed tomography (CT) scanning may be useful for early diagnosis and preoperative evaluation of the surgical approach . Optimal treatment includes broad-spectrum antimicrobial therapy and extensive cervicomediastinal and transthoracic drainage . Clamshell incision provides an excellent exposure of both thoracic cavities and all mediastinal structures with minimal morbidity . We report here a fatal case of DNM with bilateral empyema and purulent pericarditis due to an odontogenic abscess with a brief review of the literature.

Ostomy Wound Manage, 2001 Jun, 47(6), 36 - 42, 44-9
Management and prevention of venous leg ulcers: a literature-guided approach; Kunimoto BT; Managing venous leg ulcers involves management techniques that are indicated both in the treatment of all chronic leg ulcers and those that are specific to venous leg ulcers . The first step in managing venous leg ulcers is performing a holistic assessment of the patient . Once this is complete, any systemic or local factors that may affect wound healing should be addressed . This approach to managing the whole patient is critically important because if significant general wound healing factors are not treated, other specific attempts at healing the venous ulcer will be fruitless . This paper reviews nutritional supplementation, wound bed preparation, antimicrobial therapy, venous insufficiency, compression therapy, different bandage systems, therapeutic adjuncts to compression therapy, and recent advances in vascular surgery . Recurrence prevention also is discussed.

Compend Contin Educ Dent, 2001 Dec, 22(12), 1086 - 8
Surface disinfectants: read the labels; Molinari JA; There are a few basic long-standing guidelines, which can assist in the selection and safe use of chemical disinfectants (Table 2) . Even though these were developed before the current availability of many of the premixed antimicrobial sprays and wipes, they remain applicable and most important, appropriate.

Acta Vet Scand, 2001, 42(3), 365 - 75
Diagnoses and treatments in health-classified fattening herds rearing pigs all in-all out; Heinonen M et al.; This study describes diseases encountered, medications used and veterinary involvement in all in--all out finishing herds belonging to one pork production system . The finishing herds had a particular management and housing regime . The pigs originated from health classified farrowing units . Information on 207,442 pigs was collected from 595 log books . Altogether 91% of the pigs received no treatments . Four percent of the batches of pigs were given antimicrobial mass medications . The local veterinarian visited the herds on average 2.6 times during the finishing period and made the diagnoses in more than half of the cases . At least one pig was affected with arthritis or tail biting in more than half of the batches, whereas locomotory diseases were recorded in one third of the batches . All other diagnoses were encountered in 1%-13% of the batches . Only a few pigs were treated individually in the affected groups . Antimicrobial drugs were given to 8% and other medicines to 0.7% of the pigs . The diagnosis was missing at least for one pig in 29% of the batches and the information about the medicine use in 8% of the treatments was missing . The study shows that it is possible to rear finishing pigs with only a small proportion of the animals needing treatments . The need of mass medications was low, because infectious diseases affecting the whole herd were uncommon . The recommendations for antimicrobial use given by the authorities had been followed quite well . The farmers and the veterinarians should be educated in order to realise the importance of proper record keeping.

Insect Biochem Mol Biol, 2002 Apr, 32(4), 369 - 75
Immunopeptides in the defense reactions of Glossina morsitans to bacterial and Trypanosoma brucei brucei infections; Boulanger N et al.; Several dipteran insects are vectors of parasites causing major human infectious diseases . Among these, the tsetse fly, Glossina spp., is responsible for the transmission of trypanosomes, the pathogens responsible for sleeping sickness in Africa . A better understanding of insect-parasite interactions will help establish new strategies to fight this important often fatal disease . Antimicrobial peptides (AMPs) are part of the humoral immune response in insects during bacterial, fungal and parasitic infections . Here, we studied the immune response of Glossina morsitans to bacteria and to Trypanosoma brucei brucei by analyzing the synthesis of AMPs as markers of the humoral immune response . By reversed-phase chromatography, mass spectrometry analysis, Edman degradation and in vitro antimicrobial assays of the hemolymph of immune-challenged adults of G . morsitans, we identified three AMPs: a cecropin, an attacin and a defensin . These three AMPs were found to be induced upon systemic bacterial infection and also after per os infections by bacteria and parasites.

FEMS Microbiol Lett, 2002 Jan 22, 207(1), 91 - 5
Increased expression of the multidrug efflux genes acrAB occurs during slow growth of Escherichia coli; Rand JD et al.; Intrinsic antimicrobial resistance of Escherichia coli is elicited by the gene products of the multidrug efflux acrAB-tolC operon . In this paper, we have shown that acrAB is regulated as a function of the growth rate of E . coli during growth in batch and chemostat culture . In chemostat culture, expression of acrAB is inversely related to growth rate irrespective of the limiting nutrient . The level of expression of acrAB is greater under glucose limitation compared with either iron or nitrogen limitation . Increase in expression of acrAB confers a greater resistance to ciprofloxacin, and the implications for a clinical situation are discussed . Slow growth rate regulation of acrAB transcription does not require the presence of the stationary-phase sigma factor . A putative gearbox consensus sequence was identified at the -10 region of the acrAB promoter.

Br J Haematol, 2002 Mar, 116(4), 920 - 2
Adoptive therapy with monocyte-derived macrophages in the setting of high-dose chemotherapy and peripheral blood stem cell transplantation; Krause SW et al.; In an attempt to ameliorate chemotherapy-induced side-effects after transplantation of autologous peripheral blood stem cells (PBSCT), we tested the reinfusion of autologous macrophages (MAC) that are known to be potent antimicrobial effector cells and cytokine producers . Ten patients were treated with two sequential cycles of high-dose chemotherapy followed by PBSCT . Before the second cycle of PBSCT, mononuclear cells were harvested, cultured for 8 d in order to induce MAC maturation and reinfused 3 d after PBSCT without clinical problems . However, MAC infusions did not substantially alleviate the toxicity of autologous PBSCT.

J Hosp Infect, 2002 Mar, 50(3), 165 - 9
Quality indicators for antibiotic control programmes; Nathwani D et al.; Antimicrobial control measures are commonly perceived to lead to an improvement in quality of prescribing, cost-effectiveness and reduction in resistance . All three outcomes have been subject to scrutiny . As proper use of resources needs to be balanced with provision of high-quality health care, the effectiveness of control measures (antibiotic policies or formularies) must be monitored.Measurement of quality by using specific indicators has been suggested as an effective measure of performance . We describe a model for evaluating core aspects of antimicrobial control programmes, aimed at improving the quality of glycopeptide prescribing by 'appropriate use guidelines' . Prioritizing indicator settings within antimicrobial control programmes is essential if limited resources are to be used most effectively . Indicator development, evaluation and feedback ought to be multi-disciplinary to ensure ownership and long-term benefit .

Arch Pharm Res, 2002 Feb, 25(1), 28 - 38
Synthesis, antimicrobial and molluscicidal activities of new benzimidazole derivatives; Nofal ZM et al.; A series of benzimidazole Schiff's bases, thiosemicarbazides were synthesized, azole ring systems as 1,3,4-triazole, 1,3,4-oxadiazole were prepared . 1-Methylbenzimidazole incorporated to substituted dithio-carbamate, thiophenol, diethylamine via acetamido group were synthesized . A series of pyrimidinobenzimidazoles, triazinobenz-imidazoles, and 2-(acetonylamino)-1-methylbenzimidazole were prepared . The antimicrobial and molluscicidal activities of some newly prepared compounds were carried out.

Ned Tijdschr Tandheelkd, 1992 Jul, 99(7), 245 - 6
{Microbiological diagnostics in periodontal treatment}; de Graaff J et al.; Periodontal diseases are bacterial infections . The rationale for the use of microbiological diagnostics in periodontal treatment of severe periodontitis patients is discussed as well as the use of adjunct antimicrobial therapy for the elimination of specific bacterial species.

Am J Health Syst Pharm, 2002 Feb 15, 59 Suppl 1, S9 - 13
Current strategies for managing the patient with sepsis; Kuhl DA; Key elements of the current approach to treating sepsis are reviewed, and examples are given to illustrate the difficulty of designing and evaluating trials in sepsis . A patient with sepsis is likely to have symptoms characteristic of the systemic inflammatory response syndrome . Initially, ruling out noninfective causes, locating the site of infection, and obtaining cultures before beginning antimicrobial therapy are critical . Aggressive fluid resuscitation and hemodynamic support are used to restore tissue perfusion and normalize cellular metabolism . Vasopressor therapy with dopamine or norepinephrine is needed in patients unresponsive to fluid resuscitation . Dobutamine should be administered in patients whose cardiac output is inadequate despite optimization of fluids and pressors . Supportive care includes deep vein thrombosis prophylaxis, nutrition support, stress ulcer prophylaxis, and management of acute lung injury . Attempts to modify the sepsis response and improve the outcome in these patients have yielded limited benefits . Recent small studies have shown benefits with low-dose hydrocortisone in patients with refractory sepsis . One challenge in study design is that a therapy may target a subset of patients that cannot be identified at the outset . Management of patients with suspected or documented sepsis focuses on hemodynamic support, appropriate antimicrobial therapy, and other supportive care.

Am J Health Syst Pharm, 2002 Feb 15, 59(4), 349 - 54
Use of patients' own medications in small hospitals; Norstrom PE et al.; The prevalence, management, and adverse events associated with the use of a patient's personal medications in hospitals were studied . A questionnaire comprised of 17 questions was mailed in November 1999 to the pharmacy directors of a random sample of 300 small (< or = 200-bed capacity) hospitals selected from the American Hospital Association 1999 membership directory . A follow-up mailing was sent to nonrespondents in early December 1999 . The total usable response rate was 54.6% . The mean bed capacity was 76.6, and 70.8% of facilities had < or = 100 beds . Most facilities provided acute care, were nonprofit organizations, and were located in rural areas . A majority (90%) of the pharmacy directors surveyed allowed patients to use their own medications in the hospital . Elderly patients were most likely to bring their personal medications to use in the hospital, and pharmacists were the health professionals most likely to identify patients' personal medications . Circumstances in which patients were allowed to use their own medication, provided there was a physician's order, included prepackaged courses of therapy or antimicrobial courses and nonformulary medications, excluding controlled substances . Loss of personal medication and medication errors were the most frequently identified problems with allowing patients to use personal medications . Most small hospitals allowed the use of patients' personal medications; however, there was a wide variation in the circumstances for which the use of these medications was allowed.

Plant Cell, 2002 Feb, 14(2), 479 - 90
Age-related resistance in Arabidopsis is a developmentally regulated defense response to Pseudomonas syringae; Kus JV et al.; Age-related resistance (ARR) has been observed in a number of plant species; however, little is known about the biochemical or molecular mechanisms involved in this response . Arabidopsis becomes more resistant, or less susceptible, to virulent Pseudomonas syringae (pv tomato or maculicola) as plants mature (in planta bacterial growth reduction of 10- to 100-fold) . An ARR-like response also was observed in response to certain environmental conditions that accelerate Arabidopsis development . ARR occurs in the Arabidopsis mutants pad3-1, eds7-1, npr1-1, and etr1-4, suggesting that ARR is a distinct defense response, unlike the induced systemic resistance or systemic acquired resistance responses . However, three salicylic acid (SA) accumulation-deficient plant lines, NahG, sid1, and sid2, did not exhibit ARR . A heat-stable antibacterial activity was detected in intercellular washing fluids in response to Pst inoculation in wild-type ARR-competent plants but not in NAHG: These data suggest that the ability to accumulate SA is necessary for the ARR response and that SA may act as a signal for the production of the ARR-associated antimicrobial compound(s) and/or it may possess direct antibacterial activity against P . syringae.

Mol Cell Biol, 2002 Apr, 22(7), 2057 - 67
CRM1-dependent function of a cis-acting RNA export element; Popa I et al.; Viruses often contain cis-acting RNA elements, which facilitate the posttranscriptional processing and export of their messages . These elements fall into two classes distinguished by the presence of either viral or cellular RNA binding proteins . To date, studies have indicated that the viral proteins utilize the CRM1-dependent export pathway, while the cellular factors generally function in a CRM1-independent manner . The cis-acting element found in the woodchuck hepatitis virus (WHV) (the WHV posttranscriptional regulatory element {WPRE}) has the ability to posttranscriptionally stimulate transgene expression and requires no viral proteins to function . Conventional wisdom suggests that the WPRE would function in a CRM1-independent manner . However, our studies on this element reveal that its efficient function is sensitive to the overexpression of the C terminus of CAN/Nup214 and treatment with the antimicrobial agent leptomycin B . Furthermore, the overexpression of CRM1 stimulates WPRE activity . These results suggest a direct role for CRM1 in the export function of the WPRE . This observation suggests that the WPRE is directing messages into a CRM1-dependent mRNA export pathway in somatic mammalian cells.

J Immunol, 2002 Mar 15, 168(6), 3024 - 32
Antimicrobial peptides initiate IL-1 beta posttranslational processing: a novel role beyond innate immunity; Perregaux DG et al.; Human monocytes stimulated with LPS produce large quantities of prointerleukin-1beta, but little of this cytokine product is released extracellularly as the mature biologically active species . To demonstrate efficient proteolytic cleavage and export, cytokine-producing cells require a secondary effector stimulus . In an attempt to identify agents that may serve as initiators of IL-1beta posttranslational processing in vivo, LPS-activated human monocytes were treated with several individual antimicrobial peptides . Two peptides derived from porcine neutrophils, protegrin (PTG)-1 and PTG-3, promoted rapid and efficient release of mature IL-1beta . The PTG-mediated response engaged a mechanism similar to that initiated by extracellular ATP acting via the P2X(7) receptor . Thus, both processes were disrupted by a caspase inhibitor, both were sensitive to ethacrynic acid and CP-424,174, two pharmacological agents that suppress posttranslational processing, and both were negated by elevation of extracellular potassium . Moreover, the PTGs, like ATP, promoted a dramatic change in monocyte morphology and a loss of membrane latency . The PTG response was concentration dependent and was influenced profoundly by components within the culture medium . In contrast, porcine neutrophil antimicrobial peptides PR-26 and PR-39 did not initiate IL-1beta posttranslational processing . The human defensin HNP-1 and the frog peptide magainin 1 elicited export of 17-kDa IL-1beta, but these agents were less efficient than PTGs . As a result of this ability to promote release of potent proinflammatory cytokines such as IL-1beta, select antimicrobial peptides may possess important immunomodulatory functions that extend beyond innate immunity.

Br J Oral Maxillofac Surg, 2002 Feb, 40(1), 64 - 7
Craniocervical necrotizing fasciitis in Ile-Ife, Nigeria; Ndukwe KC et al.; Sixteen cases of necrotizing fasciitis were seen at the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria from 1990 to 2000 . Primary craniocervical involvement was recorded in seven patients (five men and two women) . The clinical records of five patients were sufficiently detailed to allow us to report their age, aetiology, predisposing illness, clinical features, complications, management regimen and outcome . The patients were aged 30-75 years and in four of them odontogenic infections were the cause of the condition . Hypertension, diabetes mellitus and obesity were the underlying systemic diseases in three cases and the body/angle region of the mandible was the predominant site of the infection on the face . All five cases had involvement of the neck . Mediastinal extension was recorded in three cases . Two patients had complications: one had septicaemia and renal failure and the other developed bone necrosis . Pre-existing ill health, old age, late surgical intervention, and mediastinal and thoracic extension of infection were responsible for the only death . Treatment involved frequent and multiple surgical debridement, aggressive antimicrobial treatment and control of systemic disease . Early recognition, prompt surgical intervention, and aggressive antimicrobial treatment are essential to minimize morbidity and mortality . Rapid progression of infection, financial constraints, delayed referrals from rural clinics and distance to the tertiary hospital caused problems .

Curr Opin Pediatr, 2002 Feb, 14(1), 91 - 4
Use of myeloid colony-stimulating factors in neonates with septicemia; Bernstein HM et al.; Bacterial sepsis is a major cause of neonatal morbidity and mortality . Successful management of neonatal sepsis requires early diagnosis, appropriate antimicrobial treatment, and aggressive intensive care . However, even when steps are taken appropriately, mortality rates can be high, particularly among certain subgroups, such as extremely preterm neonates and neonates with neutropenia . Multiple factors contribute to the increased susceptibility of neonates to infection, including developmental quantitative and qualitative neutrophil defects . Studies of infected animal and human neonates suggest that the use of recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) can partially counterbalance these defects and thereby reduce morbidity and mortality . However, the body of clinical evidence is currently not sufficient to recommend rhG-CSF or rhGM-CSF administration confidently as routine adjunctive treatment for neonates with sepsis.

J Neurosci, 2002 Mar 1, 22(5), 1763 - 71
Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease; Wu DC et al.; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages the nigrostriatal dopaminergic pathway as seen in Parkinson's disease (PD), a common neurodegenerative disorder with no effective protective treatment . Consistent with a role of glial cells in PD neurodegeneration, here we show that minocycline, an approved tetracycline derivative that inhibits microglial activation independently of its antimicrobial properties, mitigates both the demise of nigrostriatal dopaminergic neurons and the formation of nitrotyrosine produced by MPTP . In addition, we show that minocycline not only prevents MPTP-induced activation of microglia but also the formation of mature interleukin-1beta and the activation of NADPH-oxidase and inducible nitric oxide synthase (iNOS), three key microglial-derived cytotoxic mediators . Previously, we demonstrated that ablation of iNOS attenuates MPTP-induced neurotoxicity . Now, we demonstrate that iNOS is not the only microglial-related culprit implicated in MPTP-induced toxicity because mutant iNOS-deficient mice treated with minocycline are more resistant to this neurotoxin than iNOS-deficient mice not treated with minocycline . This study demonstrates that microglial-related inflammatory events play a significant role in the MPTP neurotoxic process and suggests that minocycline may be a valuable neuroprotective agent for the treatment of PD.

Microbes Infect, 2002 Feb, 4(2), 201 - 5
The antimicrobial activity of C-reactive protein; Szalai AJ; Recent studies in transgenic mice confirmed that C-reactive protein is protective against microbial pathogens . This is consistent with its ability in vitro to bind microbes, activate the complement classical pathway, and engage FcgammaRI and FcgammaRII . However, in transgenic mice protection also requires the alternative pathway of complement, and FcgammaRI is dispensable.

Int J Pediatr Otorhinolaryngol, 2002 Mar 15, 63(1), 1 - 13
Antimicrobial guidelines for the treatment of acute bacterial rhinosinusitis in immunocompetent children; Poole MD et al.; Acute rhinosinusitis represents a condition for which educational efforts could help minimize the inappropriate use of antibiotics, particularly for children . The majority of acute rhinosinusitis cases are of viral etiology and thus, are self limiting . Although bacterial infection complicates a small number of cases, the lack of accessibility to the sinus, the limitations of diagnostic modalities and the lack of specificity among signs and symptoms often make it difficult to determine when bacterial infection occurs . Furthermore, antimicrobial resistance among the pathogens that frequently cause bacterial infection complicates the election of empiric therapy . The Sinus and Allergy Health Partnership recently developed and published antimicrobial guidelines to provide practitioners in the US with recommendations for the diagnosis and treatment of acute bacterial rhinosinusitis . The purpose of this paper is to review the rationale behind the development of these guidelines and how they apply to the management of acute bacterial rhinosinusitis in children.

Chem Biol Interact, 2002 Mar 20, 139(3), 265 - 82
Cytotoxicity mechanisms of sodium hypochlorite in cultured human dermal fibroblasts and its bactericidal effectiveness; Hidalgo E et al.; We investigated the therapeutic efficacy of the topical antiseptic sodium hypochlorite (NaOCl) for antibacterial activity and in parallel the cytotoxicity mechanisms by which hypochlorite and the chloramines generated therefrom induce oxidative tissue damage, which further influences the wound-healing process . Human dermal fibroblasts were exposed to increasing concentrations of reagent NaOCl (0.00005-0.1%) at exposure times varying between 2 and 24 h and the protective effects of fetal calf serum (FCS) determined . Antibacterial power was studied by testing a wide range of hypochlorite concentrations (0.00025-0.5%) against four isolated bacterial species . Total bactericidal effects were observed only for 0.5%; concentration range 0.25-0.025% produced partial antimicrobial activity . The early NaOCl-produced cytotoxic action on cultured fibroblasts was cell ATP depletion which occurred at 0.00005% (with FCS 2%) followed by dose- and time-dependent decreases, reaching levels below 5% of control values . Using the 3'-{1-(phenylamino-carbonyl)-3,4-tetrazolium}-bis(4-methoxy-6-nitro)benzene sulfonic acid metabolic assay to evaluate cell death, we observed that NaOCl concentrations greater than 0.05% provoked null fibroblast survival at all exposure times assayed . Hypochlorous acid proved to exert a rapid inhibitory effect on DNA synthesis, consistent with its primary role in bacterial killing by phagocytes . Cytotoxicity produced by increasing NaOCl concentrations and assessed by measuring both mitochondrial function and cell DNA synthesis was reduced with the greatest presence of FCS (10%) in culture media.

Int J Pharm, 2002 Mar 20, 235(1-2), 121 - 7
Effect of chitosan on a periodontal pathogen Porphyromonas gingivalis; Ikinci G et al.; Local delivery systems of antimicrobial agents for treatment of the periodontal diseases received considerable attention during the past decade due to the disadvantages of the systemic administration . An ideal formulation should exhibit ease of delivery, a good retention at the application site, and a controlled release of the drug . The application of bioadhesive gels provides a long stay in the oral cavity, adequate drug penetration, high efficacy and acceptability . In dentistry and oral medicine, various applications of chitosan, which is a bioadhesive polymer have been proposed due to its favorable properties such as biocompatibility and biodegradability . The aim of this study was to determine the antimicrobial activity of chitosan formulations either in gel or film form against a periodontal pathogen, Porphyromonas gingivalis . The viscosity, bioadhesive properties and antimicrobial activity of chitosans at different molecular weight and deacetylation degree were evaluated in the absence or presence of chlorhexidine gluconate (Chx), incorporated into the formulations at 0.1 and 0.2% concentrations . The flow property of the gels were found to be suitable for topical application on the oral mucosa and to syringe into the periodontal pocket . Bioadhesion of the gels and films examined ex-vivo using fresh porcine buccal mucosa showed that both the film and gel formulations exert bioadhesive properties and was not affected by incorporation of Chx . Chitosan is shown to have an antimicrobial activity against P . gingivalis and this was higher with high molecular weight chitosan . The combination of chitosan with Chx showed a higher activity when compared to that of Chx alone, which would provide Chx application at lower concentrations thus avoiding its unwanted side effects . Chitosan films and gels seem to be promising delivery systems for local therapy of periodontal diseases with its bioadhesive property and antimicrobial activity.

Curr Treat Options Gastroenterol, 2002 Apr, 5(2), 133 - 138
Rescue Therapy for Helicobacter pylori; Leung WK et al.; Up to 35% of patients infected with Helicobacter pylori fail to respond to standard anti-H . pylori therapy . With the rising prevalence antimicrobial resistance, the failure rates of conventional proton pump inhibitor-containing triple therapy are expected to increase . Pretreatment antibiotic resistance testing should be done whenever possible to allow for tailoring of the treatment regimens . The data on second-line or rescue therapy are limited and usually are subjected to various biases and confounding factors . Switching between clarithromycin and metronidazole should be considered if repeated courses of proton pump inhibitor-containing triple therapy are used as second-line therapy in the absence of antimicrobial sensitivity testing . The prolongation of therapy duration with proton pump inhibitor, amoxicillin, and clarithromycin is ineffective for clarithromycin-resistant strains . The bismuth-containing quadruple therapy is the best salvage treatment in the absence of pretreatment antibiotic susceptibility . Furazolidone quadruple therapy (where available) and rifabutin triple therapy are salvage therapies of last resort . If these regimens fail, culture and susceptibility testing is required.

J AOAC Int, 2002 Jan-Feb, 85(1), 107 - 12
Evaluation of the use of liquid dishwashing compounds to control bacteria in kitchen sponges; Nielsen P et al.; A test procedure for evaluating the effect of adding commercial liquid hand dishwashing detergents to kitchen sponges to control microbial growth is described . Claims for this type of application are being made on dishwashing detergents throughout the world . In this evaluation, commercially available kitchen sponges were stripped of antimicrobial compounds . Sponges were then inoculated with a pool of 7 microorganisms which consisted of gram positives, gram negatives, and yeast . Inoculated sponges were treated with the detergent as recommended by the manufacturer and allowed to incubate for 16 h at ambient temperature . Surviving microorganisms were then quantitated using either the spiral or pour plate method . Tests were run using both clean sponges and sponges soiled with 0.5% nonfat dry milk (NFDM) . Untreated sponges showed stasis or slightly increased bacterial populations after the incubation period in the absence of NFDM . Significant increases of up to 3 log cfu/mL were observed for untreated sponges when soiled with NFDM . Statistically significant reductions were observed for clean sponges (99.8-99.9998%) and sponges soiled with NFDM (87.6-99.9%) when detergents making "antibacterial sponge" claims were added to the inoculated sponges . Statistically significant differences between detergents making "antibacterial sponge" claims were also observed.

Biopolymers, 2002 Apr 15, 63(5), 335 - 42
Analysis of peptide rotational diffusion by homonuclear NMR; Malliavin TE et al.; The analysis of the rotational diffusion of a molecule using homonuclear NMR is investigated . The homonuclear longitudinal and transverse cross-relaxation rates, which can be quantitatively measured using off-Resonance Rotating frame nuclear Overhauser Effect Spectroscopy (ROESY), are used to build a distribution, which exhibits a solid-state-like pattern characteristic of the diffusion tensor . The distributions of the antimicrobial peptide ranalexin in water and in 30% of trifluoracetic acid (TFE) are compared, and the peptide rotational diffusion is shown to be more isotropic in water than in 30% TFE . This difference is further supported by the analysis of NMR ranalexin conformers in 30% TFE, and by the analysis of a molecular dynamics simulation of peptide in water .

Zhonghua Yan Ke Za Zhi, 1998 May, 34(3), 211 - 4
{Intraocular penetration of topical lomefloxacin in rabbit's eyes}; Zhang Y et al.; OBJECTIVE: To measure the rabbit ocular tissue concentration of lomefloxacin (LMLX) after its topical application . METHODS: Fifteen rabbits (30 eyes) for the experiment (12 white rabbits and 3 pigmented rabbits) were divided into 5 groups . In the 1st group, 0.3% LMLX eyedrops were instilled once (1 drop each) in the 3 white rabbit's eyes . In the 2nd group, 0.3% LMLX eyedrops were instilled for 6 times (1 drop once) with an interval of 5 minutes in the 3 white rabbit's eyes . In the 3rd group, 0.3% LMLX eyedrops were instilled once (1drop each) in the 3 white rabbit's eyes after removal of corneal epithelium . In the 4th group, 0.3% LMLX eyedrops were instilled once (1 drop each) in the 3 pigmented rabbit's eyes . In the 5th group, LMLX 0.5 mg was subconjunctivally injected in the 3 white rabbit's eyes . After the administration for 30 minutes, aqueous humor was collected and the eyeball was enucleated . All measurements were performed by high-pressure liquid chromatography (HPLC) . RESULTS: In the 1st group, the mean levels of drug were 8.75 +/- 3.09 microg/g in cornea, 0.21 +/- 0.1 microg/ml in aqueous humor, and 1.49 +/- 0.39 microg/g in iris, respectively . The ocular tissue concentrations of the other groups were significantly higher than that of the 1st group . The pigmented tissue of pigmented rabbit's eyes had relatively high concentration of LMLX . CONCLUSION: All concentrations of LMLX in rabbit's eyes are above the minimum inhibitory concentration for 90% (MIC(90)) of most bacterial pathogens . LMLX has greater affinity in the pigmented tissue . These results show that LMLX may be an effective antimicrobial agent for prophylactic use in ophthalmic surgery and also for the treatment of intraocular infections due to susceptible organisms.

Mol Plant Microbe Interact, 2002 Feb, 15(2), 91 - 101
Fdb1 and Fdb2, Fusarium verticillioides loci necessary for detoxification of preformed antimicrobials from corn; Glenn AE et al.; Fusarium verticillioides is a fungus of significant economic importance because of its deleterious effects on plant and animal health and on the quality of their products . Corn (Zea mays) is the primary host for F . verticillioides, and we have investigated the impact of the plant's antimicrobial compounds (DIMBOA, DIBOA, MBOA, and BOA) on fungal virulence and systemic colonization . F . verticillioides is able to metabolize these antimicrobials, and genetic analyses indicated two loci, Fdb1 and Fdb2, were involved in detoxification . Mutation at either locus caused sensitivity and no detoxification . In vitro physiological complementation assays resulted in detoxification of BOA and suggested that an unknown intermediate compound was produced . Production of the intermediate compound involved Fdbl, and a lesion in fdb2 preventing complete metabolism of BOA resulted in transformation of the intermediate into an unidentified metabolite . Based on genetic and physiological data, a branched detoxification pathway is proposed . Use of genetically characterized detoxifying and nondetoxifying strains indicated that detoxification of the corn antimicrobials was not a major virulence factor, since detoxification was not necessary for development of severe seedling blight or for infection and endophytic colonization of seedlings . Production of the antimicrobials does not appear to be a highly effective resistance mechanism against F . verticillioides.

Tidsskr Nor Laegeforen, 2001 Nov 10, 121(27), 3201 - 6
{Can disinfectants contribute to antibiotic resistance?}; Heir E et al.; BACKGROUND: Disinfectants are widely used in medicine, veterinary medicine, and the food processing industry . Increasingly, disinfectants are included in consumer products . Broad-scale use of antiseptics and disinfectants may have detrimental ecological consequences, for instance the development of antimicrobial resistance . MATERIAL AND METHODS: We give an overview of the correlation between the use of certain antiseptics and disinfectants, bacterial resistance to these agents, and antibiotic resistance . RESULTS: The mechanisms of antibiotic and biocide resistance share many common characteristics . There are links between disinfectant resistance and antibiotic resistance . Some biocides have the ability to select for antibiotic resistant mutants and vice versa . Resistance genes are often located on transferable genetic elements that facilitate horizontal gene transfer between microorganisms . Antibiotic resistance and disinfectant resistance may be stabilized and maintained even in the absence of a direct selective pressure . Higher incidence of bacteria resistant to certain disinfectants have been reported in environments where such agents are frequently used compared to environments where they are not in regular use . Increased domestic usage of non-antibiotic antimicrobial agents may select for antibiotic-resistant bacteria of clinical significance . INTERPRETATION: The use of antiseptics and disinfectants should be restricted to products and areas where they have an essential and documented effect.

Tidsskr Nor Laegeforen, 2001 Nov 10, 121(27), 3191 - 6
{Natural antimicrobial peptides--promising new antibiotics or a problem later on?}; Vorland LH; BACKGROUND: Antimicrobial proteins and peptides are important elements of host defence that are found in virtually all living species examined so far . MATERIAL AND METHODS: This review is based on the author's own research and a search of Medline (key words: antimicrobial peptides, biochemistry, mode of action, resistance) . RESULTS: In animals, antimicrobial peptides are found on mucosal epithelial surfaces, in body fluids and in the microbicidal organelles of phagocytic cells . The peptides vary in size, structure and activity, but most are amphiphilic and positively charged . They act on a broad range of bacteria, fungi, viruses, parasites and certain tumour cells . Cationic peptides can be classified into several groups on the basis of sequence similarities, secondary and tertiary structure, function and origin . Their main acting mechanism is thought to be the disruption of the cytoplasmic membrane which kill bacteria swiftly and thoroughly . INTERPRETATION: Antimicrobial peptides are promising novel antibiotic candidates for clinical use, topically as well as systemically . So far, development of resistance against antimicrobial peptides has not been a problem, but this will have to be monitored closely in the years ahead.

Clin Diagn Lab Immunol, 2002 Mar, 9(2), 358 - 65
Invasive pneumococcal infections in Denmark from 1995 to 1999: epidemiology, serotypes, and resistance; Konradsen HB et al.; Danish nationwide surveillance data on invasive pneumococcal disease from the 5-year period from 1995 to 1999, including 5,452 isolates, are presented and described . Annual overall incidence rates, serotype distribution, and antimicrobial susceptibility patterns of the isolates were monitored . Major changes in the total annual incidence rate from 27/100,000 in 1996 to 17/100,000 in 1999 and a significant change in the proportion of invasive isolates belonging to types 1 and 12F were observed . The serotype coverage rate by the 23-valent polysaccharide vaccine among the elderly was 92.9%, and the serotype coverage rate by the 7-, 9-, and 11-valent pneumococcal conjugate vaccines among children less than 2 years old were 71.7, 75.2, and 81.4%, respectively . Invasive isolates with reduced susceptibility to penicillin or erythromycin increased from 1995 to 1999, with a high proportion of the penicillin-nonsusceptible invasive isolates originating from people 60 years old or older (57.0%) . These observations underline the importance of adequate surveillance systems of invasive pneumococcal disease to introduce and maintain national vaccine strategies and adequate antibiotic policy.

Clin Diagn Lab Immunol, 2002 Mar, 9(2), 313 - 9
Analysis of Chlamydia pneumoniae growth in cells by reverse transcription-PCR targeted to bacterial gene transcripts; Haranaga S et al.; Chlamydia pneumoniae is an obligate intracellular bacterium and has a unique development cycle consisting of an elementary body (EB) and reticular body (RB) . EBs survive in extracellular environments as well as infect susceptible host cells . However, EBs display no measurable metabolic activity . In contrast, RBs are metabolically active and can replicate in a host cell but are noninfectious . Therefore, analysis of C . pneumoniae growth in infected cells by conventional bacterial culture may not permit sufficient information about growth of the bacteria in cells . In this study, therefore, we examined the usefulness of the reverse transcription (RT)-PCR method for analysis of bacterial transcripts to evaluate C . pneumoniae growth in HEp-2 cells because the levels of bacterial gene transcripts are known to show the metabolic activity of bacteria . The transcripts for the C . pneumoniae hsp60 gene and 16S rRNA in the cells were easily detected just after infection, followed by a marked increase . In contrast, pyk and omcB transcripts slowly increased after a latent period . The hydrocortisone treatment of C . pneumoniae-infected cells induced an increase of all bacterial transcripts tested compared with the control group . The treatment of the infected cells with the antibiotic minocycline showed a selective inhibition of bacterial gene transcripts, even though the complete inhibition of EB production determined by the bacterial culture assay was evident . These results indicate that the determination of bacterial gene transcripts by RT-PCR might be a powerful method to analyze in detail growth of C . pneumoniae in host cells, particularly altered bacterial growth caused by agents such as antimicrobials.

Lett Appl Microbiol, 2002, 34(3), 168 - 72
Chitosan potentiates the antimicrobial action of sodium benzoate on spoilage yeasts; Sagoo SK et al.; AIMS: The objective of this study was to determine whether low concentrations of chitosan and benzoate in combination could be used to enhance the antimicrobial action of either compound alone against three spoilage yeasts in saline solutions . METHODS AND RESULTS: Saccharomyces exiguus, Saccharomycodes ludwigii and Torulaspora delbrueckii were suspended in 0.05 and 0.005% chitosan glutamate and 0.025% sodium benzoate, alone or in combination, in 0.9% saline solutions at pH 6.2 and 4.5 . Survivor curves were constructed from viable counts determined periodically for up to 120 min . Chitosan at 0.005% almost doubled the extent of death caused by 0.025% benzoate alone, from about 1-2 log to about 2-4 log cfu ml(-1), depending on pH and target organism . CONCLUSIONS: Chitosan (0.005%) and 0.025% sodium benzoate acted synergistically against spoilage yeasts in saline solutions . SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that the natural compound chitosan may be useful as an adjunct in the potentiation of the biocidal efficacy of antimicrobial compounds such as benzoates.

J Vet Pharmacol Ther, 2002 Feb, 25(1), 1 - 5
Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin, and orbifloxacin in dogs after single oral administration; Heinen E; The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs . Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin . Analysis was performed by an agar diffusion assay . Pharmacokinetic parameters were calculated by noncompartmental methods . All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 mug/mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively . Enrofloxacin was eliminated at a terminal half-life (t(1/2)) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h . While the area under the serum concentration-time curve of the 24-h dosing interval (AUC0--24) for marbofloxacin and orbifloxacin were similar (approximately 13 microg x h/mL), enrofloxacin attained an AUC(0-24) of 8.7 and difloxacin of 9.3 microg x h/mL . Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as C(max)/MIC (maximum serum concentration/minimum inhibitory concentration) and AUC(0-24)/MIC (area under the 24-h serum concentration--time curve/minimum inhibitory concentration) compared with other FQs.

Eur J Biochem, 2002 Mar, 269(5), 1382 - 92
Induction of (2'-5')oligoadenylate synthetase in the marine sponges Suberites domuncula and Geodia cydonium by the bacterial endotoxin lipopolysaccharide; Grebenjuk VA et al.; Recent studies have shown that the Porifera, with the examples of the demosponges Suberites domuncula and Geodia cydonium, comprise a series of pathways found also in the immune system of Deuterostomia, such as vertebrates, but are absent in Protostomia, with insects or nematodes as examples . One pathway is the (2'-5')oligoadenylate synthetase {(2-5)A synthetase} system . In the present study we show that crude extracts from tissue of S . domuncula collected from the sea display a considerable amount of (2-5)A synthetase activity; 16% of the ATP substrate is converted to the (2-5)A product, while tissue from specimens which were kept for 6 months in an aquarium shows only 1% of conversion . As aquarium animals show a lower bacterial load, those specimens were treated for the experiments with the bacterial endotoxin lipopolysaccharide (LPS); they responded to LPS with a stimulation of the (2-5)A synthetase activity . To monitor if this effect can be obtained also on the in vitro level, primmorphs which comprise proliferating and differentiating cells, were incubated with LPS . Extracts obtained from LPS-treated primmorphs also convert ATP to the (2-5)A products mediated by the synthetase . In parallel to this effect on protein level, LPS causes after an incubation period of 12 h also an increase in the steady-state level of the transcripts encoding the putative (2-5)A synthetase . It is postulated that in sponges the (2-5)A synthetase is involved in antimicrobial defense of the animals.

J Acquir Immune Defic Syndr, 2002 Mar 1, 29(3), 262 - 9
Placental inflammation and perinatal transmission of HIV-1; Mwanyumba F et al.; The effect of placental membrane inflammation on mother-to-child transmission (MTCT) of HIV-1 is reported . Placentas from HIV-1-infected women were examined as part of a perinatal HIV-1 project in Mombasa, Kenya . Polymerase chain reaction analysis was used to test for HIV-1 in the infants at birth and at 6 weeks . The maternal HIV-1 seroprevalence was 13.3% (298 of 2,235) . The overall rate of MTCT of HIV-1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV-1-positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission) . The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6% . Acute chorioamnionitis was independently associated with peripartum HIV-1 transmission but not with in utero MTCT (17.9% vs . 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2-12.5; p =.025) . Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the baby's oral cavity and a high maternal viral load in peripheral blood . The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%-22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated . We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.

Lancet Infect Dis, 2001 Dec, 1(5), 334 - 44
Emerging role of Mycoplasma pneumoniae and Chlamydia pneumoniae in paediatric respiratory-tract infections; Principi N et al.; Increased use of specialised diagnostic techniques over the past 10 years has allowed considerable new information to be obtained concerning Mycoplasma pneumoniae and Chlamydia pneumoniae infections . In children, these pathogens seem to have a more important role in causing respiratory-tract infections than previously thought; they have been associated with wheezing, and they are also frequent in children aged under 5 years . Contrary to original belief, no clinical, laboratory, or radiological findings seem to be unique to M . pneumoniae or C . pneumoniae; furthermore, there is no rapid and cost-effective diagnostic test capable of identifying these pathogens . Appropriate antimicrobial treatment of the infections they cause is needed to reduce the recurrent episodes of wheezing and other respiratory symptoms, to decrease morbidity, and to avoid the spread of the pathogens . However, a number of therapeutic issues remain unsolved.

J Med Microbiol, 2002 Mar, 51(3), 231 - 7
Susceptibility of Helicobacter pylori and its urease activity to the peroxidase-hydrogen peroxide-thiocyanate antimicrobial system; Shin K et al.; The susceptibility of Helicobacter pylori to the antimicrobial system involving lactoperoxidase, hydrogen peroxide and thiocyanate was investigated . The inhibitory effect of the system on the urease activity of H . pylori, which plays a role in its colonisation of the stomach, was also investigated . Twelve H . pylori strains examined, including 10 clinical isolates, were all inhibited by the peroxidase system in brain-heart infusion broth supplemented with fetal calf serum, but to different extents . The killing effect was observed within 3 h . Although bacterial viability recovered afterwards, there was still a clear difference between cultures incubated in the presence of the complete system and control cultures incubated in the absence of lactoperoxidase, after incubation for 24 h . The urease activity and viability of H . pylori were both inactivated by this system in phosphate buffer . These effects were dependent on the concentrations of both lactoperoxidase and hydrogen peroxide and were abolished by the addition of cysteine . Furthermore, these effects were observed when bovine lactoperoxidase was replaced by recombinant human lactoperoxidase or native or recombinant human myeloperoxidase . The peroxidase system found in saliva and milk may contribute to the host defence against H . pylori infection and inhibition of transmission via the oral route.

Lancet Infect Dis, 2001 Oct, 1(3), 156 - 64
Cationic peptides: effectors in innate immunity and novel antimicrobials; Hancock RE; Cationic antimicrobial peptides are produced by all organisms, from plants and insects to human beings, as a major part of their immediately effective, non-specific defences against infections . With the increasing development of antibiotic resistance among key bacterial pathogens, there is an urgent need to discover novel classes of antibiotics . Therefore, cationic peptides are being developed through clinical trials as anti-infective agents . In addition to their ability to kill microbes, these peptides seem to have effector functions in innate immunity and can upregulate the expression of multiple genes in eukaryotic cells . One such function might involve the dampening of signalling by bacterial molecules such as lipopolysaccharide and lipoteichoic acid.

Lancet Infect Dis, 2001 Sep, 1(2), 85 - 91
Efficacy of pneumococcal conjugate vaccines and their effect on carriage and antimicrobial resistance; Klugman KP; Pneumococcal conjugate vaccines have shown a high degree of success in preventing pneumococcal bacteraemia in children . They also reduce the acquisition of carriage of vaccine serotypes in the nasopharynx, and reduce otitis media caused by those serotypes . Non-vaccine serotypes, which can colonise vaccinated infants, are associated with otitis media in these children and lower the overall effectiveness of the vaccine to this disorder . Longer term studies, however, could show that immunised children develop immunity to a broad range of pneumococcal serotypes at a younger age than non-immunised children . Preliminary data suggest that these vaccines could reduce the burden of radiologically confirmed pneumonia . Pneumococcal conjugate vaccines interrupt the transmission of antibiotic-resistant pneumococci and thus decrease the burden of antibiotic resistance in immunised children and in their contacts . Studies are underway to assess conjugate vaccine efficacy against invasive disease, pneumonia, and all-cause mortality in developing countries, and to assess the potential use of these vaccines in adults.

J Microbiol Methods, 2002 May, 49(3), 325 - 8
Potassium release, a useful tool for studying antimicrobial peptides; Orlov DS et al.; We used an ion-selective electrode to measure potassium release from bacteria treated with antimicrobial peptides . This broadly applicable and simple technique for assessing membrane integrity deserves greater use.

Am J Surg, 2002 Jan, 183(1), 2 - 3
Treatment of Helicobacter pylori infection in patients with peptic ulcer disease; Godshall CJ; Helicobacter pylori is an organism that is thought to be important in the pathophysiology of peptic ulcer disease and gastritis . Eradication of the organism is useful in clinical cure of infected patients . Efficacious regimens generally include an antisecretory agent combined with two to three antimicrobials . The main determinant of overall cost of treatment is the rate of eradication of the organism . Impediments to patient compliance include intensive dosage schedules and drug side effects . Resistance can occur to the commonly used antibiotics but can usually be overcome with an altered regimen.

Cochrane Database Syst Rev . 2002;(1):CD002997.
Macrolides for chronic asthma; Richeldi L et al.; BACKGROUND: Asthma is a chronic disease of the airways in which inflammation of the respiratory mucosa plays a crucial role . The mechanisms responsible for the maintaining of this inflammatory response are only partially known and there is evidence that a role could be paid by chronic infection by intracellular pathogens (such as Chlamydia pneumoniae) . Macrolides are antibiotics with both antimicrobial and anti-inflammatory activities and thus their use in asthmatic patients could lead to reduction of the airways inflammation and therefore improvement of symptoms and pulmonary function . OBJECTIVES: To determine whether macrolides are effective in the management of patients with chronic asthma . SEARCH STRATEGY: We searched MEDLINE, EMBASE and CINAHL up to May 2001 . This was also supplemented by manually searching bibliographies of previously published reviews, conference proceedings, and contacting study authors . All languages were included in the initial search . SELECTION CRITERIA: Randomised, controlled clinical trials involving both children and adult patients with chronic asthma treated with macrolides for more than 4 weeks, versus placebo . DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles . Two reviewers reviewed the full text of any potentially relevant article independently . MAIN RESULTS: The initial search retrieved 95 studies . Preliminary evaluation identified 20 studies that were potentially eligible . Five (357 patients) met the entry criteria . The entry criteria for the primary trials differed, but all recruited a specific subgroup of patients (eg severe oral steroid dependent, aspirin intolerant or evidence of Chlamydia pnuemoniae infection) . There was a positive effect on symptoms (Standardised Mean Difference -1.25, 95% Confidence Intervals (CI) -1.80, -0.70) and markers of eosinophilic inflammation; eg sputum eosinophils Weighted Mean difference -78.5, 95%CI -90.8, -66.1) . Tests of oral corticosteroid-sparing effects have not yet been performed on the newer agents such as roxithromycin and clarithromycin . REVIEWER'S CONCLUSIONS: Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma . Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection.

Clin Microbiol Infect . 1997 Feb;3 Suppl 4:S60.
Therapy of sepsis; Young LS; The term 'sepsis' is often used synonymously with 'infection' or 'bacteremia' . Additional definitions, e.g . 'systemic inflammatory response syndrome', have been proposed . These terms have been employed to establish entry criteria for clinical trials of antibiotic therapy and adjunctive therapies . It may be appropriate to utilize these descriptions when initiating therapy of suspected bacterial infections, since culture confirmation is often not available for days after initial clinical presentation . Empiric antibiotic therapy is now the rule rather than the exception for febrile hospitalized patients . No antimicrobial agent is superior for all major clinical situations and thus history and physical examination are critical factors which guide the clinician . Guidelines have been derived for the initial empiric management of serious infection . While these were initially refined for the immunocompromized host, they may be considered generally applicable for the hospitalized patient with a suspected serious systemic bacterial infection . Currently, monotherapy with agents such as cefepime, ceftazidime, imipenem/cilastatin and meropenem has been sanctioned on the basis of their broad antimicrobial coverage and stability to clinically important beta-lactamases (although there is considerable variation from one compound to another) . Perception of local epidemiologic patterns is a major factor in the selection of initial antibacterial therapy for hospital-acquired infection.

Clin Microbiol Infect, 1997 Jun, 3 Suppl 3, S55 - S58
Prevention of acute otitis media; Rodrigo C; Breast-feeding, using family or small-group day care for infants and toddlers and avoiding exposure to household tobacco smoke are the main preventive measures against acute otitis media (AOM) . It is also useful to immunize children who have recurrent otitis media with the influenza and the pneumococcal vaccines . Antibiotic prophylaxis is the most effective method to reduce the frequency of new episodes of otitis in children with recurrent AOM, but it should be used with caution . Tympanostomy tube placement and/or adenoidectomy can be considered as options in some situations . Now, probably, the best initial steps to take to prevent new episodes of otitis in children with recurrent AOM are antimicrobial treatment of each individual AOM episode and, in certain cases, antibiotic prophylaxis for short periods when an upper respiratory tract infection is present.

Am J Epidemiol, 2002 Mar 1, 155(5), 472 - 7
Use of oral antimicrobials decreases serum enterolactone concentration; Kilkkinen A et al.; The lignan enterolactone, a phytoestrogen, may protect against hormone-dependent cancers and cardiovascular diseases . It is produced by the intestinal microflora from dietary precursors . Because of the pronounced impact of antimicrobials on the intestinal microflora, the authors examined whether serum enterolactone concentration is affected by previous use of oral antimicrobials . Enterolactone was measured by time-resolved fluoroimmunoassay in 2,753 Finnish men and women aged 25--64 years who participated in a cross-sectional national survey in 1997 . Background information was collected by self-administered questionnaire, and data on antimicrobial treatment were gathered from the nationwide prescription database of the Social Insurance Institution . Serum enterolactone concentration was significantly lower in those who had used oral antimicrobials up to 12--16 months before serum sampling than in nonusers (16.4 vs . 19.3 nmol/liter) . The concentration was associated with the number of treatments and the time from the last treatment . Modest differences were present between various antimicrobials . The authors' findings support the crucial role of gut microflora in the metabolism of lignans . Furthermore, recent use of antimicrobials should be considered when the association between serum enterolactone concentration and risk of chronic diseases is studied.

Clin Microbiol Infect, 1996 Feb, 2(3), 186 - 191
Pharmacokinetics of once-daily amikacin in pediatric patients; Belfayol L et al.; OBJECTIVE: To study the pharmacokinetic parameters of a once-daily regimen of amikacin (15 mg/kg) in association with other antimicrobial agents in 35 children with severe Gram-negative infections . METHODS: A Bayesian approach was developed to optimize the amikacin regimen . The predictive performance was assessed by computing bias and precision . Each patient was evaluated for toxicity after 5 days of treatment . RESULTS: Peak amikacin concentrations on days 2 and 5 of therapy averaged 31.3 plus minus 9.0 mg/L and 32.4 plus minus 7.4 mg/L, respectively . To achieve peak serum concentrations between 30 and 40 mg/L, individualized dosage was necessary in 19 of 35 children . The pharmacokinetic parameters showed large interindividual variations, with a mean half-life of 2 h and a mean volume of distribution of 0.36 L/kg . No nephrotoxicity was observed in any of the children . After individualization of dosage on the basis of one measurement of peak concentration, no significant differences were observed between predicted and subsequently measured amikacin concentrations . CONCLUSIONS: Once-daily dosage of amikacin (15 mg/kg) is well tolerated in pediatric patients; however, a loading dose of 20 mg/kg is recommended to achieve a therapeutic peak value between 30 and 40 mg/L . Initial serum monitoring is essential in a population such as children, with wide interpatient variability . Using the Bayesian approach, the amikacin regimen in children can then be predicted with minimal bias and good precision.

Clin Microbiol Infect, 1996 Jun, 1 Suppl 2, S27 - S29
Antibacterial treatment of community-acquired pneumonia: the role of therapeutic agents other than the macrolides; Ronald AR et al.; The optimal guidelines for the treatment of community-acquired pneumonia are not well established, and the relevant pathogen is often unknown . Initial choice of an antimicrobial agent should depend on the initial severity of the patient's illness, site of acquisition, age, coexisting illness and treatment setting . Few reliable studies have been performed to establish the supremacy of any antibiotic agent in this condition, either for ambulatory or hospital treatment.

Clin Microbiol Infect, 1995 Feb, 1(2), 127 - 133
Comparison of macrorestriction analysis of genomic DNA by pulsed-field gel electrophoresis and ribotyping with conventional methods for differentiation of Escherichia coli 0124 isolates; Llovet T et al.; OBJECTIVE: To evaluate the usefulness of different phenotypic and genotypic markers for epidemiological typing of enteroinvasive Escherichia coli 0124 (EIEC 0124) . METHODS: Seven sporadic EIEC 0124 isolates and 22 isolates from two different outbreaks were characterized . Chromosomal deoxyribonucleic acid (DNA) macrorestriction analysis with XbaI resolved by pulsed-field gel electrophoresis (PFGE) and ribotyping with each of the three restriction endonucleases BglII EcoRI, and ClaI were compared with biotyping, antimicrobial susceptibility patterns and plasmid profiles . RESULTS: Biotypes and antimicrobial resistance profiles of the outbreak-associated strains showed considerable variation, thereby limiting the usefulness of such phenotypic markers . Only 57% of the sporadic isolates harbored plasmids . Three different ribotypes based on 5 to 7 bands were recorded among sporadic isolates whereas all outbreak-associated strains showed the same ribotype . BglII appeared to give the best discrimination whereas EcoRI and ClaI provided no additional information . Sporadic EIEC 0124 isolates showed a marked diversity of macrorestriction patterns (similarity coefficient 58 to 93%) and five different patterns were detected . In contrast, the outbreak isolates were closely related (similarity coefficient 90 to 100%) . Genomic DNA macrorestriction analysis correlated well with ribotyping, but PFGE was more discriminating . CONCLUSIONS: PFGE is a useful method for epidemiological comparison and differentiation of EIEC 0124 isolates.

J Infect Dis, 2002 Feb 15, 185 Suppl 1, S25 - 36
The shikimate pathway and its branches in apicomplexan parasites; Roberts CW et al.; The shikimate pathway is essential for production of a plethora of aromatic compounds in plants, bacteria, and fungi . Seven enzymes of the shikimate pathway catalyze sequential conversion of erythrose 4-phosphate and phosphoenol pyruvate to chorismate . Chorismate is then used as a substrate for other pathways that culminate in production of folates, ubiquinone, napthoquinones, and the aromatic amino acids tryptophan, phenylalanine, and tyrosine . The shikimate pathway is absent from animals and present in the apicomplexan parasites Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum . Inhibition of the pathway by glyphosate is effective in controlling growth of these parasites . These findings emphasize the potential benefits of developing additional effective inhibitors of the shikimate pathway . Such inhibitors may function as broad-spectrum antimicrobial agents that are effective against bacterial and fungal pathogens and apicomplexan parasites.

Mol Cell Biol, 2002 Mar, 22(6), 1926 - 35
BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore; Risso A et al.; BMAP-28, a bovine antimicrobial peptide of the cathelicidin family, induces membrane permeabilization and death in human tumor cell lines and in activated, but not resting, human lymphocytes . In addition, we found that BMAP-28 causes depolarization of the inner mitochondrial membrane in single cells and in isolated mitochondria . The effect of the peptide was synergistic with that of Ca(2+) and inhibited by cyclosporine, suggesting that depolarization depends on opening of the mitochondrial permeability transition pore . The occurrence of a permeability transition was investigated on the basis of mitochondrial permeabilization to calcein and cytochrome c release . We show that BMAP-28 permeabilizes mitochondria to entrapped calcein in a cyclosporine-sensitive manner and that it releases cytochrome c in situ . Our results demonstrate that BMAP-28 is an inducer of the mitochondrial permeability transition pore and that its cytotoxic potential depends on its effects on mitochondrial permeability.

Fitoterapia, 2002 Feb, 73(1), 92 - 4
Antimicrobial activity and cytotoxicity of Aerva lanata; Chowdhury D et al.; Aerva lanata whole plant showed interesting antimicrobial activities (ethyl acetate and methanol extracts) and significant cytotoxic properties (petroleum ether, ethyl acetate and methanol extracts).

An Esp Pediatr, 2002 Mar, 56(3), 204 - 7
{Predictive factors of efficacy in antimicrobial prophylaxis for acute recurrent otitis media}; Prim Espada MP et al.; OBJECTIVE: A prospective study was designed to assess the most relevant prognostic factors influencing outcome in children treated with antibiotics for recurrent acute otitis media (AOM) . MATERIALS AND METHODS: A prospective study was performed in 69 patients with recurrent AOM who received prophylactic treatment in the Pediatric Otorhinolaryngology Section of our hospital between January 1998 and May 1999 . In all patients, 17 variables were registered: age, sex, family history of recurrent AOM, history of prematurity, history of allergies, use of day care centers, household smokers, maternal smoking, coincidence with dental eruption, symptoms of upper respiratory obstruction (snoring, breathing through the mouth, obstructive tonsils), episodes of tonsillitis per year, age at first AOM episode, season in which prophylaxis was started, and characteristics of neonatal feeding (breast or bottle feeding and position).ResultsThe mean age was 35.3 months (range: 9-120 months) . There were 38 boys (55.1 %) and 31 girls (44.9 %) . The factors related to a more favorable response to treatment were lower age at the first AOM episode (p 0.004) and a positive family history of AOM (p 0.047) . CONCLUSIONS: The children that benefitted most from the prophylactic schedules for recurrent AOM were those that had the first episode at an earlier age and who had a positive family history of the disease.

Clin Microbiol Infect, 1997 Jun, 3(3), 365 - 368
Susceptibility testing by E-test and agar dilution of 30 strains of Legionella spp . isolated in Portugal; Marques T et al.; OBJECTIVE: To evaluate the activity of erythromycin, roxithromycin, ciprofloxacin, doxycycline, sulfamethoxazole trimethoprim and rifampin against 32 strains of Legionella spp . under different testing conditions . METHODS: Minimum inhibitory concentrations (MICs) were determined by the E-test (Ab Biodisk, Solna, Sweden) and agar dilution reference technique (National Committee for Clinical Laboratory Standards (NCCLS), 1990) on two different media, buffered charcoal yeast extract agar (BCYE-alpha) and buffered yeast extract agar (BYE-alpha), under 48- and 72-h incubation, without CO2 . RESULTS: All the antimicrobial agents were inhibited by BCYE-alpha agar . The MIC90 values on BYE-alpha were lower than those on BCYE-alpha but the variation factor was not the same: ciprofloxacin and rifampin, followed by erythromycin, suffered the greatest inhibition by the charcoal in the culture medium . Except for ciprofloxacin and rifampin, the 72-h MIC90 readings were always higher than the 48-h results whenever the agar dilution method was used . The E-test results showed slight variations with some, but not all, antibiotics . The most active agents against the 32 Legionella strains tested were rifampin and ciprofloxacin . CONCLUSIONS: BCYE-alpha is not suitable for susceptibility testing of Legionella spp . The E-test method on BYE-alpha agar with 48-h incubation is recommended.

Clin Microbiol Infect, 1997 Jun, 3(3), 306 - 316
Evaluation of tumor necrosis factor-alpha, interleukin-6 and C-reactive protein plasma levels as predictors of bacteremia in patients presenting signs of sepsis without shock; Byl B et al.; OBJECTIVE: To evaluate the sensitivity of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) plasma measurement to detect bacteremia in patients presenting sepsis signs, and to evaluate the potential benefit of such measurement in terms of early antimicrobial therapy initiation . METHODS: Plasma was obtained from 166 hospitalized patients for whom blood cultures were drawn for sepsis . Clinical data and antimicrobial therapies were noted . IL-6, TNF and C-reactive protein (CRP) were measured . The sensitivities of these markers were retrospectively compared with the accuracy of the attending physician in initiating empirical antimicrobial therapy . The setting was an 850-bed university hospital . RESULTS: Thirty-four bacteremias and 69 non-bacteremic infections were noted . In 63 others, no infection was documented . Median (range) IL-6 plasma levels in the three groups of patients were 462 (15--50 850), 189 (<15--38 300) and 91 (<10--13 750) pg/mL, respectively (p<0.01) . The corresponding TNF-alpha plasma levels were 37.5 (<15--2400), 15 (<15--240) and 15 (<15--200) pg/mL, respectively (p<0.01) . CRP plasma levels were 10.7 (<0.6--30.2), 10.3 (<0.6--34.4) and 7.3 (<0.6--20.9) mg/dL, respectively (p=0.12) . With respect to these three parameters, IL-6 and TNF-alpha appear better than CRP for predicting bacteremia . Clinical features resulted in starting empirical antimicrobial therapy in only 62% of the bacteremic patients . On the other hand, 68% of these bacteremic patients had high IL-6 plasma levels (>200 pg/mL) . A combination of clinical features and high IL-6 levels would have permitted early treatment for 82% of the bacteremic patients . CONCLUSIONS: IL-6 and TNF-alpha thus appear to be useful and earlier markers of bacteremia in septic patients . By contrast, CRP is neither sensitive nor specific in this setting.

Clin Microbiol Infect, 1997 Jun, 3(3), 283 - 288
Do the new lipid formulations of amphotericin B really work?
Tang CM, Bowler IC.
Over the past two years, there has been a dramatic rise in the prescription of lipid formulations of amphotericin B at our hospital . These compounds now account for a significant proportion of all expenditure on antimicrobial agents . We therefore conducted a review of the efficacy of the lipid formulations of amphotericin B . Only one randomized controlled trial has assessed the efficacy of any of these formulations in treating proven fungal infections, and this is only available in abstract form . Most of the available evidence on the use of lipid formulations is in the form of case series . There are therefore limited data to justify the widespread use of these compounds, and we believe that there are few circumstances when their administration is warranted . We suggest that local policies should be drawn up for the prescription of lipid formulations of amphotericin B, and, until more compelling data are available, that these drugs only be administered after discussion with microbiologists or infectious diseases physicians.

Med Hypotheses, 2002 Jan, 58(1), 34 - 46
Streptomycin revisited: molecular action in the microbial cell; Kornder JD; The key event for antimicrobial action begins when streptomycin binds to the 30S subunit (S12 protein) of a ribosome . Lysine 42 and lysine 87 are involved . It is proposed that antagonism of acetyl coenzyme A carboxylase by streptomycin results in faulty fatty acids, lipids and derivatives marked exclusively for cell membrane synthesis . Streptomycin-sensitive growing cells are fatally wounded when defective membranes leak K(+) ions, then amino acids, nucleotides, oligonucleotides and proteins as increasing amounts of streptomycin enter the cell .

Br Dent J, 2002 Feb 9, 192(3), 157 - 60
A survey of antibiotic prescribing by maxillofacial consultants for dental extractions following radiotherapy to the oral cavity; Kanatas AN et al.; OBJECTIVES: To analyse the antibiotic prescribing trends for exodontia and minor oral surgery in patients with a history of radiotherapy . Also, to evaluate the use of hyperbaric oxygen as a separate modality in the prevention of osteoradionecrosis . DESIGN: A survey of antibiotic prescribing involving the analysis of a questionnaire which included the management of three patients with a history of head and neck malignancy . METHOD: The heads of the departments in each unit in the UK were sent a closed-response questionnaire . Antibiotic prescribing was assessed in three case scenarios . Case one referred to a patient that had surgery alone as part of the management of head and neck cancer, who needed the surgical removal of second molar roots . Case two referred to a patient that had surgery and adjuvant radiotherapy as part of the management of head and neck cancer, and needed the same procedure as in case one . Case three included a patient with a history of surgery and adjuvant radiotherapy, who required the extraction of three mobile and periodontally-involved lower incisors . Consultants were also asked about the use of hyperbaric oxygen in the patients who had radiotherapy as part of their treatment strategy . RESULTS: A total of 109 questionnaires were sent to all the Maxillofacial Units in the UK . The response rate was 73% . In patients with a history of radical surgery alone for the management of head and neck cancer, 20% of the surgeons advocated pre-operative antibiotics for the surgical removal of lower posterior teeth . In contrast, in the patient with a history of adjuvant radiotherapy 86% supported pre-operative antimicrobial use for the surgical removal of the same teeth . In the extraction of mobile and periodontally involved lower incisors in the previously irradiated patient, 63% of the clinicians supported pre-extraction antibiotics . Postoperative antibiotics were advocated in 52% in the first case, 89% in the second case and 71% in the third case . 34% of the clinicians advocated hyperbaric oxygen for surgical removal of posterior teeth and 15% for the extraction of mobile anterior teeth . CONCLUSIONS: The use of peri-extraction antibiotics was favoured among oral and maxillofacial surgeons . There was little enthusiasm towards the use of hyperbaric oxygen as a prophylactic measure, alone or in conjunction with an antimicrobial regime . Control randomised trials that will measure the effectiveness of hyperbaric oxygen and the appropriate use of antibiotics for prophylaxis in pre- and post-operative regimes are necessary to evaluate the use of these modalities.

AIDS Alert, 2002 Feb, 17(2), 13 - 6
Evidence shows hepatitis C virus is playing major role in AIDS deaths; Beta-defensin 1 gene variability among non-human primates; Dipartimento di Biologia Animale e dell'Uomo, Universita di Torino, Via Accademia Albertina 13/17, 10123 Turin, ItalyDefensins are a recently described family of peptides that play an important role in innate immunity . Recent studies have shown that defensins exhibit a broad spectrum of antimicrobial activities against bacteria and fungi . Three families have been identified so far in mammals, alpha-defensins, beta-defensins and theta-defensins, presumably derived from a common ancestral defensin . A long-term study on the evolution of these multigene families among primates has been undertaken to investigate: (1) the degree of interspecific differentiation; (2) the genetic mechanisms responsible for the variability of these molecules; and (3) the possible role of different environmental factors in their evolution . Nucleotide sequences have been obtained from great and lesser apes, several African and Asian catarrhine monkeys and one New World monkey . A comparison of rates of synonymous and nonsynonymous (amino-acid changing) nucleotide substitution indicates that the primate beta-defensin 1 gene evolved under a pattern of random nucleotide substitution as predicted by the neutral theory of molecular evolution . These results are not consistent with the hypothesis that the primate beta-defensin 1 gene has diversified in response to changes in the microbial species to which a given host is exposed . Analyses of interpecific variability have yielded some insights about the pattern of molecular evolution of the gene among primates . Humans and great apes present high levels of sequence similarity, differing in only one amino acid residue in the mature peptide . Compared with these taxa, hylobatids and cercopithecids exhibit 3-4 amino acid substitutions, some of which increase the net charge of the active molecule.

Annu Rev Immunol, 2002, 20, 197 - 216 Epub 2001 Oct 04.
Innate immune recognition; Janeway CA Jr et al.; The innate immune system is a universal and ancient form of host defense against infection . Innate immune recognition relies on a limited number of germline-encoded receptors . These receptors evolved to recognize conserved products of microbial metabolism produced by microbial pathogens, but not by the host . Recognition of these molecular structures allows the immune system to distinguish infectious nonself from noninfectious self . Toll-like receptors play a major role in pathogen recognition and initiation of inflammatory and immune responses . Stimulation of Toll-like receptors by microbial products leads to the activation of signaling pathways that result in the induction of antimicrobial genes and inflammatory cytokines . In addition, stimulation of Toll-like receptors triggers dendritic cell maturation and results in the induction of costimulatory molecules and increased antigen-presenting capacity . Thus, microbial recognition by Toll-like receptors helps to direct adaptive immune responses to antigens derived from microbial pathogens.

Am J Ophthalmol, 2002 Mar, 133(3), 398 - 9
Polymerase chain reaction diagnosis in fungal keratitis caused by Alternaria alternata; Ferrer C et al.; PURPOSE: To contribute toward assessing the effectiveness of polymerase chain reaction as a rapid method in diagnosis of torpid keratitis caused by opportunistic fungi . METHODS: Interventional case report . A 50-year-old man with a corneal abscess in the right eye treated for a period of 6 months with different combinations of broad-spectrum antibiotics and steroids was referred to our center . Corneal scraping was taken for microbiological study, including classic cultures and polymerase chain reaction . Amplified DNA was sequenced to identify the pathogen . RESULTS: Polymerase chain reaction amplification was negative for Acanthamoeba species and positive for fungi . The sequence analysis showed Alternaria alternata as the causal agent in 24 hours . Cultures confirmed the identification in 10 days . CONCLUSION: Polymerase chain reaction amplification with subsequent DNA-typing was revealed to be a useful method for detection of ocular pathogens such as A . alternata involved in cases of torpid keratitis, even in the presence of broad-spectrum antimicrobial therapy.

Curr Med Chem, 2002 Jan, 9(1), 127 - 43
Pathogen inactivation in blood products; Wainwright M; A combination of the economic importance of blood as a resource and the advent of the AIDS epidemic has led to a requirement for improved pathogen screening techniques for donated blood . However, due to window periods where infective agents cannot be detected, the ability to disinfect of blood and its derivatives plasma, platelets and red blood cell concentrates has assumed great importance . Whereas conventional disinfection techniques such as solvent-detergent treatment or ultra-violet irradiation may be employed in plasma or protein concentrates, the collateral damage associated with such treatments disallows their use with cellular fractions . In many ways the pathogen selectivity required here is akin to standard antimicrobial chemotherapy but is complicated by the requirement for activity against the full range of microbes--viruses, bacteria, yeasts and protozoa--rather than simply antibacterial or antiviral etc . The recent problems due to prion agents in the blood supply mean that such agents should also be included in any proposed disinfecting regimen . Several new approaches to microbial disinfection have been proposed by academia and the "blood industrials" : targeted chemotherapy, photochemotherapy and photodynamic antimicrobial chemotherapy.

Life Sci, 2002 Jan 18, 70(9), 1075 - 84
Isolation of lilin, a novel arginine- and glutamate-rich protein with potent antifungal and mitogenic activities from lily bulbs; Wang H et al.; From the dried bulbs of the lily (Lilium brownii), a protein with strong antifungal and mitogenic activities was isolated . It also exhibited an inhibitory action on the activity of HIV-1 reverse transcriptase . The protein was single-chained and possessed a molecular weight of 14.4 kDa and an N-terminal sequence distinct from chitinases and antimicrobial proteins of garlic, leek and onion which belong to a family closely related to lily . However, there was a small degree of resemblance to cyclophilins and a considerable extent of identity to the 6.5 kDa arginine/glutamate-rich polypeptide from Luffa cylindrica seeds . A nearly homogeneous preparation was obtained after the extract was fractionated on DEAE-cellulose and Affi-gel Blue gel since subsequent chromatography on Mono S and Superdex 75 both yielded a single peak.

Vet Res Commun, 2002 Jan, 26(1), 11 - 9
Comparative in vitro activity of 16 antimicrobial agents against Actinobacillus pleuropneumoniae; Yoshimura H et al.; Sixteen antimicrobial agents were tested for their activity against 68 isolates of Actinobacillus pleuropneumoniae by determining the minimum inhibitory concentrations (MICs) . Ceftiofur and the fluoroquinolones danofloxacin and enrofloxacin were the most active compounds, with a MIC for 90% of the isolates (MIC90) of (0.05 microg/ml . The MIC90 values of benzylpenicillin, amoxicillin and aspoxicillin were 0.78 units/ml, 0.39 microg/ml and < or = 0.05 microg/ml, respectively . Three isolates (4.4%) were resistant to penicillins, but aspoxicillin was as active as ceftiofur against the susceptible isolates, with MICs of < or = 0.05 microg/ml for all isolates . Resistance to oxytetracycline, chloramphenicol and thiamphenicol occurred in 22 (32.4%), 14 (20.6%) and 15 (22.1%) of the isolates, respectively . Doxycycline was more active than oxytetracycline, with a MIC90 of 1.56 microg/ml as against 25 microg/ml . Florfenicol was not only as active as thiamphenicol, with a MIC for 50% of the isolates (MIC50) of 0.39 microg/ml, but also active against thiamphenicol-resistant isolates . All the isolates were susceptible to florfenicol . All the isolates were also susceptible to gentamicin, spectinomycin, tilmicosin, colistin and tiamulin . Of these, spectinomycin was the least active, with a MIC50 of 25 microg/ml, followed by tiamulin, with a MIC50 of 6.25 microg/ml . Of the 68 isolates tested, 49 (72.0%) were of serotype 2; 14 (20.5%) were of serotype 1; 2 each (3.0%) were of serotypes 5 and 6; and one was of serotype 7 . Of the isolates, 23 (33.8%) were resistant to one or more of the major antibiotics . Antibiotic resistance was found only infrequently among serotype 2, with 5 (10.2%) of 49 isolates being resistant to chloramphenicol and/or oxytetracycline, while it occurred in 18 (94.7%) of the 19 isolates of other serotypes.

Ann Otol Rhinol Laryngol, 2002 Feb, 111(2), 135 - 41
Antimicrobial defensin peptides of the human nasal mucosa; Lee SH et al.; Defensins, a prominent group of antimicrobial peptides, are an important component of the innate immune response, particularly at mucosal surfaces that are vulnerable to colonization by potential pathogens . The present study was undertaken to investigate the expression of defensins in inferior turbinate mucosa of normal subjects and inferior turbinate mucosa and nasal polyps of patients with chronic sinusitis . Expression of beta-defensin 1 and 2 and alpha-defensin 5 and 6 messenger RNAs (mRNAs) was investigated by reverse transcriptase-polymerase chain reaction, and their expression level was semiquantitatively evaluated by dot blot hybridization . Immunohistochemical analysis was used for detection of alpha-defensins 1, 2, and 3 in tissue sections . Beta-defensin 1 mRNA was expressed in all tissue samples, at levels that did not differ significantly . Beta-defensin 2 mRNA was detected in the turbinate mucosa and nasal polyps of patients with chronic sinusitis, but not in normal mucosa . Its expression level was significantly higher in nasal polyps than in turbinate mucosa . Alpha-defensin 5 and 6 mRNAs were not expressed in any tissues, but alpha-defensins 1, 2, and 3 were detected in all tissue samples obtained from patients with chronic sinusitis . These results suggest that beta-defensin 1 may play a constitutive role in nasal defenses, whereas alpha-defensins 1, 2, and 3 and beta-defensin 2 may be induced in response to local infection or inflammation.

J Immunol, 2002 Mar 1, 168(5), 2356 - 64
Endotoxin-neutralizing antimicrobial proteins of the human placenta; Kim HS et al.; Microbial colonization and infection of placental tissues often lead to adverse pregnancy outcomes such as preterm birth, a leading cause of neonatal morbidity and mortality . The fetal membranes of the placenta, a physical and active barrier to microbial invasion, encapsulate the fetus and secure its intrauterine environment . To examine the innate defense system of the human placenta, antimicrobial peptides were isolated from the fetal membranes of human placenta and characterized biochemically . Two salt-resistant antimicrobial host proteins were purified to homogeneity using heparin-affinity and reversed-phase HPLC . Characterization of these proteins revealed that they are identical to histones H2A and H2B . Histones H2A and H2B showed dose-dependent inhibition of the endotoxin activity of LPS and inhibited this activity by binding to and therefore blocking both the core and lipid A moieties of LPS . Consistent with a role for histones in the establishment of placental innate defense, histones H2A and H2B were highly expressed in the cytoplasm of syncytiotrophoblasts and amnion cells, where the histone proteins were localized mainly to the epithelial surface . Furthermore, culturing of amnion-derived WISH cells led to the constitutive release of histone H2B, and histones H2A and H2B contribute to bactericidal activity of amniotic fluid . Our studies suggest that histones H2A and H2B may endow the epithelium of the placenta with an antimicrobial and endotoxin-neutralizing barrier against microorganisms that invade this immune-privileged site.

Bioorg Med Chem Lett, 2002 Mar 11, 12(5), 723 - 7
New 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane thiosemicarbazones-thiocarbonohydrazones: cell growth inhibitory, antiviral and antimicrobial activity evaluation; Kolocouris A et al.; The new thiosemicarbazones and thiocarbonohydrazones derived from 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane were synthesized and evaluated for their inhibitory effect on tumor cell proliferation and their antiviral and antimicrobial activity . Thiosemicarbazone inhibited tumor cell proliferation (GI50's range: 2.4-100 microM and mean GI50 43.9 microM against various human leukemic cell lines) while thiosemicarbazone and thiocarbonohydrazone 5d exhibited significant inhibition of tumor cell proliferation (GI50's range 2.3-23.6 microM and mean GI50 7.2 microM for and GI50's range 2.4-32.4 microM and mean GI50 12.8microM for ) . These GI50 values are comparable to that of 2-acetylpyridine thiosemicarbazone an important lead in TSC's family . The compounds did not afford specific activity against any of the viruses tested when examined at non-toxic concentrations . A weak activity was found for thiocarbonohydrazones against Gram-(+) bacteria (MIC(50) 117.3 and 133 microM, respectively) . Using a combination of molecular mechanics calculations and NOE spectroscopy it was shown that the parent compounds and have opposite configuration around C=N bond . Whether this difference in structure can be correlated with the biological activity will be investigated in future studies.

Eur J Cancer, 2002 Mar, 38 Suppl 4, S82 - 7
Management of infection in cancer patients . studies of the EORTC International Antimicrobial Therapy Group (IATG); Viscoli C; EORTC International Antimicrobial Therapy Group; Infection remains an important cause of morbidity and mortality in cancer patients, especially those undergoing chemotherapy for haematological malignancies . The practice of instituting an empirical broad-spectrum antibiotic therapy as soon as possible after the onset of fever has substantially reduced the clinical impact of this complication . In the last 25 years, the International Antimicrobial Therapy Group of the European Organisation for Research and Treatment of Cancer (EORTC-IATG) have published nearly 30 articles and a number of abstracts on several facets of the epidemiology and management of infection in cancer patients . With a progressive methodological refinement, the EORTC-IATG trials have established the standard for the management of febrile neutropenia, both by setting methodologies and definitions and by testing several antibiotic regimens that are active and effective for this indication . With the aim of supporting a more rational use of antibiotics in cancer patients, the most recent trials have dealt with the management of low risk patients, showing the safety and feasibility of oral therapy.

Diagn Microbiol Infect Dis, 2002 Feb, 42(2), 145 - 7
In vitro activity of 11 antimicrobial agents, including gatifloxacin and GAR936, tested against clinical isolates of Mycobacterium marinum; Rhomberg PR et al.; In vitro activities of 11 antimicrobial agents were determined using Etest (AB BIODISK, Solna, Sweden) against 37 clinical isolates of Mycobacterium marinum . The most potent agent (MIC(50,) 0.047 microg/mL) was trimethoprim/sulfamethoxazole, but only 91.9% would be categorized as susceptible . Several agents had a complete spectrum of activity including gatifloxacin (MIC(90,) 0.38 microg/mL), minocycline (MIC(90,) 2 microg/mL), tetracycline (MIC(90,) 2 microg/mL) and amikacin (MIC(90,) 3 microg/mL) . The new glycylcycline, GAR936, had a similar potency (MIC(90,) 3 microg/mL) to that of the parent minocycline compound (MIC(90,) 2 microg/mL), but the range of MIC values extended to 24 microg/mL . Numerous options appear to exist for the contemporary therapy of M . marinum infections including some newer fluoroquinolones and derivatives of tetracycline (doxycycline, minocycline, GAR936).

J Antibiot (Tokyo), 2001 Dec, 54(12), 1054 - 9
Tripropeptins, novel antimicrobial agents produced by Lysobacter sp . I . Taxonomy, isolation and biological activities; Hashizume H et al.; Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp . The differences among these components are in the lengths of the alkyl side chain . Tripropeptins are active against Gram-positive bacteria including MRSA in vitro . Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.

Crit Care Nurs Q, 2001 Aug, 24(2), 64 - 77; quiz 2 p following 77
Infected wound management: advanced technologies, moisture-retentive dressings, and die-hard methods; Campton-Johnston S et al.; Wound infection is a significant problem for the complicated, critically ill patient . A critical care patient's plan of care can be challenging enough without complicating it with the additional comorbidity of a wound infection . Wound infection delays wound closure, disrupts wound tensile strength; increases hospital length of stay and costs; and escalates the patient's risk of bacteremia, sepsis, multisystem organ failure, and death . The goal is to reduce and eliminate the wound infection before it leads to such drastic consequences, especially in the age of antibiotic-resistant organisms . It is paramount to identify classic and not-so-obvious signs and symptoms of wound infections, correctly collect a wound specimen, and assist in appropriate systemic and topical wound management . Techniques to prevent wound infection and reduce bioburden include nontoxic wound cleansing, debridement of necrotic tissue, proper antibiotic management, and appropriate use of moisture-retentive dressings . Advanced technologies in moisture-retentive dressings include sustained-release silver and cadexomer iodine antimicrobial dressings and negative-pressure wound therapy . Accurate wound assessment, knowledge of new technologies, and applying current wound care standards to clinical practice will assist the critical care nurse in treating and preventing wound infections.

Clin Excell Nurse Pract, 2000 Jan, 4(1), 13 - 7
Community-acquired pneumonia: a case study; Meister J; Community-acquired pneumonia (CAP) is an infectious disease commonly seen in the primary care environment . CAP is ranked as the sixth leading cause of death in the United States . It affects more than 10 million individuals per year and accounts for 500,000-1,000,000 hospital admissions . Precise diagnosis of CAP continues to be complex . Despite enormous advances in serologic analysis and antimicrobial development, at least 50% of causative pathogens are not identified . This article presents a case report of a white female in her seventies diagnosed with CAP and emphasizes the need for early detection, immunization, and prompt interventions to reduce morbidity and mortality rates . This case brings to light the dilemma practitioners can face when treating high-risk populations on an outpatient basis.

Int J Cancer, 2002 Mar 10, 98(2), 297 - 309
Inhibition of cell proliferation, invasion, tumor growth and metastasis by an oral non-antimicrobial tetracycline analog (COL-3) in a metastatic prostate cancer model; Lokeshwar BL et al.; Antibiotic forms of tetracycline exhibit antitumor activity in some tumor models . However, their low in vivo efficacy and associated morbidity limit their long-term application in cancer therapy . This report appraises the efficacy of doxycycline (DC) and non-antimicrobial, chemically modified tetracyclines (CMTs) against prostate cancer . Both DC and several CMTs inhibited prostate tumor cell proliferation in vitro . Some of the CMTs were significantly more potent than DC . One of the CMTs, 6-deoxy, 6-demethyl, 4-de-dimethylamino tetracycline (CMT-3, COL-3), was the most potent inhibitor (50% inhibition dose {GI(50)} < or = 5.0 ,microg/ml) . Exposure of tumor cells to CMT-3 induced both apoptosis and necrosis . Mitochondrial depolarization and increased levels of reactive hydroxyl radicals were also observed in cells treated with CMT-3 . Cell cycle arrest at the G(0)/G(1) compartment was observed in CMT-3- and DC-treated cells . DC and CMTs also inhibited the invasive potential of the tumor cells in vitro, from 10% (CMT-6) to >90% (CMT-3) . CMT-3 and DC decreased matrix metalloproteinase (MMP)-2, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 secretion in treated cultures and inhibited activity of secreted MMPs, CMT-3 was a stronger inhibitor . Daily oral gavage of DC and CMT-3 inhibited tumor growth and metastasis in the Dunning MAT LyLu rat prostate tumor . Decreases in tumor growth (27-35%) and lung metastases were observed (28.9 +/- 15.4 sites/animal {CMT-3-treated} versus 43.6 +/- 18.8 sites/animal {DC-treated} versus 59.5 +/- 13.9 {control}; p < 0.01} . A delay in tumor growth (27 +/- 9.3%, p < 0.05), reduction in metastases (58 +/- 8%) and decrease in tumor incidences (55 +/- 9%, CMT-3-treated) were also observed, when rats were predosed for 7 days . No significant drug-induced morbidity was observed in any of the animals . These results, along with a recently concluded clinical trial, suggest a potential use of CMT-3 as an oral, nontoxic drug to treat metastatic prostate and other cancers .

Vet Microbiol, 2002 Apr 2, 85(4), 353 - 9
Susceptibility of Arcanobacterium pyogenes from different sources to tetracycline, macrolide and lincosamide antimicrobial agents; Trinh HT et al.; Chlortetracycline, oxytetracycline, and the macrolide, tylosin, are extensively used for growth promotion and disease prophylaxis in the cattle and swine industries in the US . Arcanobacterium pyogenes, a common inhabitant of the mucosal surfaces of cattle and swine, is also a pathogen associated with a variety of infections in these animals . A broth microdilution technique was used to determine the antimicrobial susceptibility of 48 A . pyogenes isolates to macrolides, lincosamides and tetracyclines . The MIC50 and MIC90 for chlortetracycline were 0.12 and 8 mg/l, respectively . Similarly, the MIC50 and MIC90 for oxytetracycline were 0.25 and 8 mg/l, while the MIC50 and MIC90 for tetracycline were 0.25 and 16 mg/l, respectively . The MIC50 and the MIC90 were < or = 0.06 and >64 mg/l, respectively, for erythromycin, tylosin and clindamycin . This resistance pattern indicated that some of these A . pyogenes isolates may carry an MLS(B) resistance determinant . A . pyogenes isolates (12.5%) were resistant to erythromycin, and this percentage doubled when MICs were performed following induction with erythromycin . Of the 48 A . pyogenes isolates, 25 and 41.7% were resistant to MLS(B) antimicrobial agents and the tetracycline derivatives, respectively . MLS(B) resistance was present in 22.2 and 35.3% of A . pyogenes isolates of bovine (n=27) or porcine (n=17) origin . In contrast, 70.6% of porcine isolates were resistant to the tetracyclines, compared with 25.9% of bovine isolates . These data suggest that a large proportion of A . pyogenes field isolates may be resistant to these commonly used antimicrobial agents.

Steroids, 2002 Mar, 67(3-4), 291 - 304
The synthesis of spermine analogs of the shark aminosterol squalamine; Shu Y et al.; Aminosterols isolated from the dogfish shark Squalus acanthias are promising therapeutic agents in the treatment of infection and cancer . One of these, MSI-1436, has been shown to possess antimicrobial activity slightly better than squalamine . In this study, a series of analogs of MSI-1436 have been synthesized from stigmasterol . The 7 alpha-hydroxy substituent of MSI-1436 was either omitted or the stereochemistry modified to the 7 beta position . Also, analogs of MSI-1436 with 24-sulfate, 24-amino, and 24-hydroxy substituents were synthesized in order to assess the importance of the side chain functional group on antimicrobial activity . All of the analogs possess significant antimicrobial activity, suggesting that substitution at C7 and C24 of the aminosterols plays a minor role in their antimicrobial potency.

Eur J Biochem, 2002 Feb, 269(4), 1190 - 8
The solution structure of gomesin, an antimicrobial cysteine-rich peptide from the spider; Mandard N et al.; Gomesin is the first peptide isolated from spider exhibiting antimicrobial activities . This highly cationic peptide is composed of 18 amino-acid residues including four cysteines forming two disulfide linkages . The solution structure of gomesin has been determined using proton two-dimensional NMR (2D-NMR) and restrained molecular dynamics calculations . The global fold of gomesin consists in a well-resolved two-stranded antiparallel betasheet connected by a noncanonical betaturn . A comparison between the structures of gomesin and protegrin-1 from porcine and androctonin from scorpion outlines several common features in the distribution of hydrophobic and hydrophilic residues . The N- and C-termini, the betaturn and one face of the betasheet are hydrophilic, but the hydrophobicity of the other face depends on the peptide . The similarities suggest that the molecules interact with membranes in an analogous manner . The importance of the intramolecular disulfide bridges in the biological activity of gomesin is being investigated.

Eur J Biochem, 2002 Feb, 269(4), 1181 - 9
SMAP-29 has two LPS-binding sites and a central hinge; Tack BF et al.; The CD spectra of SMAP-29, an antimicrobial peptide from sheep, showed disordered structure in aqueous buffers, and significant helicity in membrane-like environments, including SDS micelles, lipopolysaccharide (LPS) dispersions, and trifluoroethanol buffer systems . A structure determined by NMR in 40% perdeuterated trifluoroethanol indicated that residues 8-17 were helical, residues 18-19 formed a hinge, and residues 20-28 formed an ordered, hydrophobic segment . SMAP-29 was flexible in 40% trifluoroethanol, forming two sets of conformers that differed in the relative orientation of the N-terminal domain . We used a chromogenic Limulus assay to determine the EC50 of the peptide (the concentration that bound 50% of the added LPS) . Studies with full-length and truncated SMAP-29 molecules revealed that each end of the holopeptide contained an LPS-binding domain . The higher affinity LPS-binding domain was situated in the flexible N-terminal portion . LPS binding to full-length SMAP-29 showed positive cooperativity, so the EC50 of the peptide (2.6 microm) was considerably lower than that of the individual LPS-binding domains . LPS-binding studies with a mixture of truncated peptides revealed that this cooperativity was primarily intramolecular (i.e . involving the N- and C-terminal LPS-binding sites of the same peptide molecule) . CAP-18{106 -142}, an antimicrobial cathelicidin peptide of rabbits, resembled SMAP-29 in that it contained N- and C-terminal LPS-binding domains, had an EC50 of 2.5 microm, and bound LPS with positive cooperativity . We conclude that the presence of multiple binding sites that function cooperatively allow peptides such as SMAP-29 and CAP-18 to bind LPS with high affinity.

Clin Microbiol Infect, 1999 May, 5(5), 262 - 269
Multicenter study of the in vitro activity of cefepime in comparison with five other broad-spectrum antibiotics against clinical isolates of Gram-positive and Gram-negative bacteria from hospitalized patients in Switzerland; Wust J et al.; OBJECTIVE: To assess the in vitro susceptibility of clinical isolates to cefepime and five other antimicrobial agents with broad-spectrum activity . METHODS: The minimal inhibitory concentrations of 1521 Gram-positive cocci and 3170 Gram-negative rods were determined by the Etest procedure . RESULTS: The susceptibilities were as follows . Gram-positive bacteria: cefepime, 92.7%; ceftazidime, 60.5%; ceftriaxone, 87.8%; imipenem, 92.6%; amikacin, 56.5%; ciprofloxacin, 72.5% . Gram-negative bacteria: cefepime, 97.8%; ceftazidime, 94.3%; ceftriaxone, 83.1%; imipenem, 95.7%; amikacin, 96.6%; ciprofloxacin, 95.8% . CONCLUSIONS: Cefepime had the best activity when compared with the other broad-spectrum beta-lactams ceftazidime, ceftriaxone, imipenem, and the non-beta-lactams amikacin and ciprofloxacin.

Clin Microbiol Infect, 1999 Apr, 5(4), 205 - 212
In vitro activity, postantibiotic effect and human monocyte activity of grepafloxacin against Legionella species; Dubois J et al.; OBJECTIVE: To determine the in vitro antimicrobial activity, postantibiotic effect (PAE) and human monocyte activity of grepafloxacin compared with sparfloxacin, ciprofloxacin, clarithromycin, erythromycin and rifampicin against 181 strains of Legionella pneumophila, nine strains of L . micdadei, 10 strains of L . dumoffii, seven strains of L . longbeachae and seven other Legionella strains . METHODS: MICs were determined by standard agar dilution using buffered yeast extract (BYE) agar . PAE and human monocyte activity were determined by standard culture techniques . RESULTS: Grepafloxacin, sparfloxacin and rifampicin were the most active agents against L . pneumophila (MIC90 </=0.016 mg/L for most strains tested) . Grepafloxacin was more active than erythromycin against L . dumoffii and L . longbeachae and more active than both erythromycin and clarithromycin against L . micdadei and isolates of other Legionella spp . The PAE of grepafloxacin against erythromycin-susceptible L . pneumophila (2.62 h) was higher than that of sparfloxacin (0.88 h), erythromycin (0.93 hours) and clarithromycin (0.72 h) . Against erythromycin-resistant L . pneumophila, the PAE of grepafloxacin (4.18 h) was higher than those of all the other antibiotics tested . Grepafloxacin, sparfloxacin, ciprofloxacin and clarithromycin inhibited the growth of all L . pneumophila strains and other erythromycin-resistant Legionella spp . in human monocytes . However, only grepafloxacin and ciprofloxacin prevented regrowth or killed L . pneumophila after removal of extracellular antibiotic . CONCLUSIONS: Grepafloxacin showed effective antibacterial activity against the Legionella spp . tested, and has a PAE and activity within human monocytes that suggest it may be useful in the treatment of lower respiratory tract infections caused by Legionella spp.

Clin Microbiol Infect, 1999 Jan, 5(1), 37 - 46
Bacterial and epidemiologic study of the resistance to oxyiminocephalosporins in Escherichia coli in a French hospital; Lepelletier D et al.; OBJECTIVE: To understand the mechanisms and epidemiology of resistance to oxyiminocephalosporins in Escherichia coli over a 2-year period in a French hospital . METHODS: Forty-four strains, resistant or intermediately resistant to one of the oxyiminocephalosporins or aztreonam, were collected from 35 patients . MIC determinations were carried out for the 44 isolates using a panel of beta-lactam antibiotics, and characterization of the beta-lactamases they produced by isoelectric focusing and catalytic activity measurement . Extended-spectrum beta-lactamase production was studied by use of the double disk diffusion test . Conjugation experiments were used to search for plasmidic cephalosporinase . An epidemiologic study was then performed, by use of molecular typing of the strains with an ERIC-PCR method and a case-control analysis . RESULTS: Less than 1% of all the E . coli isolates at our hospital showed decreased susceptibility to oxyiminocephalosporins . Only three of the 44 isolates showed synergy between clavulanate and a third-generation cephalosporin and produced an extended-spectrum beta-lactamase . For the other strains, a beta-lactamase with a highly basic isoelectric point was detected . Spectrophotometric measures confirmed that most of these isolates were AmpC hyper-producers . No plasmidic cephalosporinase could be detected by conjugation experiments . Molecular typing showed all isolates to be different, except for two strains isolated in two patients of the same hospital unit, and for the repeated isolates of some patients . When 20 case patients were compared to 40 randomly selected control patients, prior receipt of an antimicrobial and more specifically of a beta-lactam agent was significantly associated with case patients . CONCLUSIONS: Although it appears to be very rare, the resistance to broad-spectrum cephalosporins needs our attention, because of the high frequency of E . coli infections and beta-lactam use in their treatment.

Proc Natl Acad Sci U S A, 2002 Feb 19, 99(4), 2152 - 7
Constitutive expression of a single antimicrobial peptide can restore wild-type resistance to infection in immunodeficient Drosophila mutants; Tzou P et al.; One of the characteristics of the host defense of insects is the rapid synthesis of a variety of potent antibacterial and antifungal peptides . To date, seven types of inducible antimicrobial peptides (AMPs) have been characterized in Drosophila . The importance of these peptides in host defense is supported by the observation that flies deficient for the Toll or Immune deficiency (Imd) pathway, which affects AMP gene expression, are extremely susceptible to microbial infection . Here we have developed a genetic approach to address the functional relevance of a defined antifungal or antibacterial peptide in the host defense of Drosophila adults . We have expressed AMP genes via the control of the UAS/GAL4 system in imd; spatzle double mutants that do not express any known endogenous AMP gene . Our results clearly show that constitutive expression of a single peptide in some cases is sufficient to rescue imd; spatzle susceptibility to microbial infection, highlighting the important role of AMPs in Drosophila adult host defense.

Proc Natl Acad Sci U S A, 2002 Feb 19, 99(4), 2129 - 33
Discovery of five conserved beta -defensin gene clusters using a computational search strategy; Schutte BC et al.; The innate immune system includes antimicrobial peptides that protect multicellular organisms from a diverse spectrum of microorganisms . beta-Defensins comprise one important family of mammalian antimicrobial peptides . The annotation of the human genome fails to reveal the expected diversity, and a recent query of the draft sequence with the blast search engine found only one new beta-defensin gene (DEFB3) . To define better the beta-defensin gene family, we adopted a genomics approach that uses hmmer, a computational search tool based on hidden Markov models, in combination with blast . This strategy identified 28 new human and 43 new mouse beta-defensin genes in five syntenic chromosomal regions . Within each syntenic cluster, the gene sequences and organization were similar, suggesting each cluster pair arose from a common ancestor and was retained because of conserved functions . Preliminary analysis indicates that at least 26 of the predicted genes are transcribed . These results demonstrate the value of a genomewide search strategy to identify genes with conserved structural motifs . Discovery of these genes represents a new starting point for exploring the role of beta-defensins in innate immunity.

Proc Natl Acad Sci U S A, 2002 Feb 19, 99(4), 1813 - 8
Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1; Cole AM et al.; Human bone marrow expresses a pseudogene that encodes an antimicrobial peptide homologous to rhesus monkey circular minidefensins (delta-defensins) . We prepared the putative ancestral human peptide by solid-phase synthesis and named it "retrocyclin." Retrocyclin did not cause direct inactivation of HIV-1, and its modest antibacterial properties resembled those of its rhesus homologs . Nevertheless, retrocyclin had a remarkable ability to inhibit proviral DNA formation and to protect immortalized and primary human CD4(+) lymphocytes from in vitro infection by both T-tropic and M-tropic strains of HIV-1 . Confocal fluorescent microscopy studies performed with BODIPY-FL-labeled RC-101, a close analog of retrocyclin, showed that the peptide formed patch-like aggregates on the surface of CD4(+) cells . These findings suggest that retrocyclin interferes with an early stage of HIV-1 infection and that retrocyclin-like agents might be useful topical agents to prevent sexually acquired HIV-1 infections.

Mol Pharmacol, 2002 Mar, 61(3), 637 - 48
Identification of ligand-binding regions of P-glycoprotein by activated-pharmacophore photoaffinity labeling and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry; Ecker GF et al.; Energy dependent efflux pumps confer resistance to anticancer, antimicrobial, and antiparasitic drugs . P-glycoprotein (Pgp, ABCB1) mediates resistance to a broad spectrum of antitumor drugs . Compounds that themselves are nontoxic to cells have been shown to act as inhibitors of Pgp . The mechanism of binding and transport of low-molecular-mass ligands by Pgp is still incompletely understood . This study introduces a series of propafenone-related photoaffinity ligands, which combine high specificity and selectivity for Pgp with high labeling efficiency . Molecules are intrinsically photoactivatable in the arylcarbonyl group, which represents a pharmacophoric substructure for this group of ligand molecules . A detailed study of the structure-activity relationship for this type of photoligand is presented . In subsequent experiments, these ligands were used to characterize the drug-binding domain of propafenone-type analogs . Matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry shows that propafenone-type ligands preferentially label fragments assigned to putative transmembrane segments 3, 5, 6, 8, 10, 11, and 12 . Labeled fragments are also identified in a highly charged region of 15 amino acids in the second cytoplasmic loop . This region corresponds to the so-called EAA-like motif, which has been proposed to play a role in the interaction between transmembrane domain and nucleotide binding domain of peroxisomal ATP-binding cassette transporters . In addition, a region in cytoplasmic loop 3 and between TM12 and the N terminus of the Walker A sequence of NBD2 are labeled by the ligands . Therefore, a number of confined protein regions contribute to the drug-binding domain of propafenone-type analogs.

Biochim Biophys Acta, 2002 Feb 15, 1559(2), 160 - 70
Translocation of protegrin I through phospholipid membranes: role of peptide folding; Drin G et al.; The protegrin PG-1, belonging to the family of beta-stranded antimicrobial peptides, exerts its activity by forming pores in the target biological membranes . Linear analogues derived from PG-1 do not form pores in the phospholipid membranes and have been used successfully to deliver therapeutic compounds into eucaryotic cells . In this paper, the translocation of PG-1 and of a linear analogue through artificial phospholipid membranes was investigated, leading to a possible mechanism for the activity of these peptidic vectors . We report here that {12W}PG-1, a fluorescent analogue of PG-1, is able to translocate through lipid bilayers and we demonstrate that this property depends on its secondary structure . Our results agree with the recent mechanism proposed for the translocation and permeabilisation activities of several helical and beta-stranded peptides . In addition, our data corroborate recent work suggesting that certain protegrin-derived vectors enter into endothelial cells by adsorptive-mediated endocytosis.

Biochim Biophys Acta, 2002 Feb 15, 1559(2), 145 - 59
Modes of membrane interaction of a natural cysteine-rich peptide: viscotoxin A3; Coulon A et al.; Among the very homologous family of alpha- and beta-thionins, known for their antimicrobial activity, the viscotoxin subfamily differs from other members because it is cytotoxic against tumoral cells but weakly hemolytic . We studied the interactions between the most active of these toxins, viscotoxin A3 (VA3), and model membranes made of phosphatidylcholine and phosphatidylserine (PS), the major zwitterionic and acidic phospholipids found in eukaryotic cells . Monolayer studies showed that electrostatic forces are essential for the interaction and are mainly involved in modulating the embedding of the toxin in the PS head group region . This in turn induces membrane stiffening, as shown by fluorescence polarization assays with 1,6-diphenyl-1,3,5-hexatriene and its derivatives . Moreover, vesicle permeabilization analyses showed that there are two modes of interaction, which are directly related to the stiffening effect and depend on the amount of VA3 bound to the surface of the vesicles . We propose an interaction model in which the embedding of VA3 in the membrane induces membrane defects leading to the gradual release of encapsulated dye . When the surfaces of the vesicles are saturated with the viscotoxin, complete vesicle destabilization is induced which leads to bilayer disruption, all-or-none encapsulated dye release and rearrangement of the vesicles.

Curr Infect Dis Rep, 2002 Feb, 4(1), 35 - 43
Chlamydia pneumoniae and Cardiovascular Disease; Kolia M et al.; Chlamydia pneumoniae, a respiratory pathogen, has been suggested as a risk factor for cardiovascular disease . Epidemiologic data are very controversial . Histopathologic and microbiologic studies have established an association between atherosclerosis and presence of C . pneumoniae, consistently finding C . pneumoniae DNA and antigens in atherosclerotic arteries . C . pneumoniae has been cultured from atherosclerotic arteries in several centers . An etiologic role for C . pneumoniae in initiation, acceleration of atherosclerosis, and/or acute ischemia remains debatable . In vitro studies have shown that C . pneumoniae can induce foam cell formation, low-density lipoprotein oxidation, and proinflammatory and procoagulant cytokine expression . Animal models of de novo initiation or enhancement of atherosclerosis have been developed . Preliminary trials of secondary prevention of coronary artery disease complications by antimicrobial agents show modest results . Better diagnostic tools, more diverse animal models, and clinical trials of primary prevention are needed . Meanwhile, results of ongoing large clinical trials on secondary prevention are eagerly awaited, but may not be definitive.

J Am Chem Soc, 2002 Feb 27, 124(8), 1606 - 14
Ketopremithramycins and ketomithramycins, four new aureolic acid-type compounds obtained upon inactivation of two genes involved in the biosynthesis of the deoxysugar moieties of the antitumor drug mithramycin by Streptomyces argillaceus, reveal novel insights into post-PKS tailoring steps of the mithramycin biosynthetic pathway; Remsing LL et al.; Mithramycin is an aureolic acid-type antimicrobial and antitumor agent produced by Streptomyces argillaceus . Modifying post-polyketide synthase (PKS) tailoring enzymes involved in the production of mithramycin is an effective way of gaining further information regarding the late steps of its biosynthetic pathway . In addition, new "unnatural" natural products of the aureolic acid-type class are likely to be produced . The role of two such post-PKS tailoring enzymes, encoded by mtmC and mtmTIII, was investigated, and four novel aureolic acid class drugs, two premithramycin-type molecules and two mithramycin derivatives, were isolated from mutant strains constructed by insertional gene inactivation of either of these two genes . From data bank comparisons, the corresponding proteins MtmC and MtmTIII were believed to act as a C-methyltransferase involved in the production of the D-mycarose (sugar E) of mithramycin and as a ketoreductase seemingly involved in the biosynthesis of the mithramycin aglycon, respectively . However, gene inactivation and analysis of the accumulated products revealed that both genes encode enzymes participating in the biosynthesis of the D-mycarose building block . Furthermore, the inactivation of MtmC seems to affect the ketoreductase responsible for 4-ketoreduction of sugar C, a D-olivose . Instead of obtaining premithramycin and mithramycin derivatives with a modified E-sugar upon inactivation of mtmC, compounds were obtained that completely lack the E-sugar moiety and that possess an unexpected 4-ketosugar moiety instead of the D-olivose at the beginning of the lower deoxysaccharide chain . The inactivation of mtmTIII led to the accumulation of 4E-ketomithramycin, showing that this ketoreductase is responsible for the 4-ketoreduction of the D-mycarose moiety . The new compounds of the mutant strains, 4A-ketopremithramycin A2, 4A-keto-9-demethylpremithramycin A2, 4C-keto-demycarosylmithramycin, and 4E-ketomithramycin, indicate surprising substrate flexibility of post-PKS enzymes of the mithramycin biosynthetic pathway . Although the glycosyltransferase responsible for the attachment of D-mycarose cannot transfer the unmethylated sugar to the existing lower disaccharide chain, it can transfer the 4-ketoform of sugar E . In addition, the glycosyltransferase MtmGIV, which is responsible for the linkage of sugar C, is also able to transfer an activated 4-ketosugar . The oxygenase MtmOIV, normally responsible for the oxidative cleavage of the tetracyclic premithramycin B into the tricyclic immediate precursor of mithramycin, can act on a substrate analogue with a modified or even incomplete trisaccharide chain . The same is true for glycosyltransferases MtmGI and MtmGII, both of which partake in the formation and attachment of the A-B disaccharide in mithramycin.

J Vet Med Sci, 2002 Jan, 64(1), 71 - 3
Antimicrobial susceptibility of pathogenic Escherichia coli isolated from pigs in Korea; Choi C et al.; The in vitro susceptibilities of 285 isolates of Escherichia coli from preweaned and postweaned pigs with diarrhea and edema disease were tested with the 15 commonly used antimicrobial drugs by an agar dilution minimal inhibitory concentration procedure according to National Committee for Clinical Laboratory Standards (NCCLS) guidelines . All E . coli isolates tested in this study belonged to enterotoxigenic E . coli, attaching and effacing E . coli, or Shiga toxin-producing E . coli . Field isolates had low MIC90 for ceftiofur (1 microg/ml) . No correlation in antimicrobial resistance was found in three types of E . coli.

Pharm Dev Technol, 2002 Jan, 7(1), 49 - 58
Sorption of benzoic acid, sorbic acid, benzyl alcohol, and benzalkonium chloride by flexible tubing; Bahal SM et al.; Earlier studies using methylparaben, propylparaben, and several types of flexible tubing showed that the parabens are sorbed by a number of commonly used tubing . The sorption increased with increase in time of contact and the tubing surface area . The temperature and pH ranges tested did not affect sorption . Current studies evaluated other commonly used antimicrobial preservatives used in oral, parenteral, opthalmic, nasal, and other pharmaceutical products . These preservatives include benzoic acid, sorbic acid, benzyl alcohol, and benzalkonium chloride . Results show that all preservatives, except benzalkonium chloride, are sorbed by several types of flexible tubing . After 24 hr, some types of tubing sorbed over 40% of benzoic acid, benzyl alcohol, and about 30% of sorbic acid . Significant losses were observed within a few hours . No sorption of benzalkonium chloride occurred in the tubing tested . Three different types of fluoropolymer resin tubing, Teflon (flourinated ethylene propylene (FEP), Teflon perfluoroalkoxy) (PFA) and Teflon polytetrafluoroethylene (PTFE, NXT), fluoropolymer FEP laminated Tygon tubing, and Zelite do not sorb any of the preservatives . Silicone tubing shows the highest sorption of preservatives . After 120 hr, as much as 64% of the preservative is sorbed by some tubing . Detailed studies using silicone tubing show that the sorption increases with increase in surface area at 25 degrees C, and increasing the temperature to 40 degrees C shows little change in sorption . At the concentration range generally used in formulations, the concentration of the preservative has no significant effect on sorption . Refilling the tubing with fresh preservative solution after contact with preservative solution for 168 hr still causes extensive sorption of the preservative . Desorption studies indicate that the sorbed preservatives are desorbed in water to a limited extent over 120 hr . Results are important in situations where short or extended interruptions occur in the processing and filling of products . This can lead to decreased and variable results due to residence of the solution in the tubing.

Arch Pharm (Weinheim), 2001 Dec, 334(12), 381 - 7
Synthesis, antimicrobial, and alkylating properties of 3-phosphonic derivatives of chromone; Budzisz E et al.; Dimethyl 2,6-dimethyl-4-oxo-4H-chromen-3-yl-phosphonate (1a) and dimethyl 6-methyl-2-phenyl-4-oxo-4H-chromen-3-yl-phosphonate (1b) were synthesized and reacted with primary aliphatic amines to yield title compounds 4-6 . Their antibacterial properties against Gram-positive and Gram-negative bacteria strains were tested by the MIC method . Four of seventeen tested compounds (1d, 3, 4a, and 4b) exhibit detectable activity against S . aureus . Some representative examples of newly synthesized compounds were tested for their alkylating properties in vitro in the Preussmann test . Compounds 1a, 1c, 1d, 3, 5d, and 6a possess highly alkylating activity toward standard derivative 4-(4'-nitrobenzyl)pyridine (NBP).

Kansenshogaku Zasshi, 2002 Jan, 76(1), 41 - 50
{Studies on efficient methods for detection of Legionella species from environmental water by use of its selective media}; Kasuga O et al.; To examine the optimal pH range for growth on media, growth of Legionella spp . on its selective media, BCYE alpha, WYO alpha and MWY agar media, in a pH range of 6.0-8.0 (at 0.5 intervals) was compared . The growth of two strains of L . pneumophila and one strain of L . micdadei on a WYO alpha agar supplemented with some selecting antimicrobial agents was markedly inhibited at all pH range except 6.0 and 7.0, suggesting a narrow optimal pH range for growth of these species compared to the BCYE alpha without selecting antimicrobioal agents . Vancomycin (VCM) added to the selective agar suppressed the growth of some Legionella spp . depending on the concentration . However, the extent of suppression was different among species and/or strains of Legionella spp . The selectivity for species other than Legionella spp . was also affected similarly by VCM concentration added to their media, suggesting that it is important to use proper amounts of the selecting antimicrobial agent depending on the species and/or strains of Legionella spp . or the other species in water samples . Amphothericin B (AMPH-B) added to a selective medium, MWY agar, in the concentration of 80 micrograms/ml hardly affected the growth of Legionella spp . examined, but effectively inhibited the growth of fungal strains identified as Aspergillus sp., Trichoderma sp., Scolecobasidium sp . and Mucor sp . which were isolated from cooling-tower water samples together with Legionella spp . Furthermore, the growth of a combination culture of one each of the 4 strains of isolated fungi and one each of the 3 strains of Legionella spp . was examined at various concentration of AMPH-B . Addition of AMPH-B to the selective medium at the concentration of 80 micrograms/ml suppressed the growth of spreading fungi, permitting the growth of Legionella spp . to allow efficient detection of the species.

FEBS Lett, 2002 Feb 13, 512(1-3), 47 - 51
The orientation of the antibiotic peptide maculatin 1.1 in DMPG and DMPC lipid bilayers . Support for a pore-forming mechanism; Chia CS et al.; Maculatin 1.1 is an antimicrobial peptide isolated from the Australian tree frog Litoria genimaculata that adopts an amphipathic, alpha-helical structure in solution . Its orientation and conformation when incorporated to pre-formed DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) and DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) vesicles was determined using polarised Fourier transform infrared-attenuated total reflection infrared and deuterium exchange experiments . For DMPG membranes, our results show insertion of 70% of the maculatin 1.1 molecules, with an angle of insertion of approximately 35 degrees to the membrane normal and with a predominant alpha-helical structure . These results suggest that maculatin 1.1 acts through a pore-forming mechanism to lyse bacterial membranes . A similar degree of insertion in DMPG (65%) and alpha-helical structure was observed for a biologically inactive, less amphipathic maculatin 1.1 analogue, P15A, although the helix tilt was found to be greater (46 degrees) than for maculatin 1.1 . Similar experiments performed using DMPC liposomes showed poor insertion, less than 5%, for both maculatin 1.1 and its analogue . In addition, the shape of the amide I band in these samples is consistent with alpha-helix, beta-structure and disordered structures being present in similar proportion . These results clearly show that maculatin 1.1 inserts preferentially in negatively charged membranes (DMPG) which mimic the negatively charged membrane of Gram-positive bacteria . We attribute the high percentage of insertion of the biologically inactive analogue in DMPG to the fact that its concentration on the membrane surface in our experiments is likely to be much higher than that found in physiological conditions.

Br J Clin Pharmacol, 2002 Feb, 53(2), 163 - 71
Management of Helicobacter pylori eradication--the influence of structured counselling and follow-up; Al-Eidan FA et al.; AIMS: Helicobacter pylori (H . pylori) eradication rate varies according to the treatment regimen used and other factors, e.g . antimicrobial resistance and patient compliance . The aim of the present study was to evaluate the influence of patient counselling and follow-up on H . pylori eradication rates and to document the effectiveness of a 1 week eradication regimen consisting of lansoprazole (30 mg once daily), amoxicillin (1 g twice daily) and clarithromycin (500 mg twice daily) . METHODS: Seventy-six dyspeptic patients, who at endoscopy were found to have gastritis, duodenitis or ulceration, and a positive H . pylori urease test, were recruited . Patients were randomly assigned to an intervention group (n = 38) or a control group (n = 38) . Intervention patients received their medicines via the hospital pharmacy and were counselled (and followed up) by a hospital pharmacist . Control patients were given a standard advice sheet and referred to their GP who prescribed the same therapy . RESULTS: Intervention patients exhibited a statistically significant improvement in the H . pylori eradication rate (94.7% vs 73.7%; P = 0.02) and compliance (92.1% vs 23.7; P < 0.001) . Of the 64 H . pylori eradicated patients, 62 were able to eliminate their antisecretory medication compared with only 12 of the H . pylori persistent patients (P < 0.001) . A pharmacoeconomic evaluation indicated that counselling and follow-up reduced the direct costs of eradication by approximately 30 UK pounds per patient . CONCLUSIONS: Structured patient counselling and follow-up can have a significant effect on H . pylori eradication rates and should be a routine part of therapy.

Ugeskr Laeger, 2002 Feb 4, 164(6), 750 - 4
{Why is QT interval interesting?}; Elming H et al.; A prolonged Q-T interval is generally associated with increased risk of ventricular arrhythmias, like torsade de pointes, and death . It has recently become apparent that not only antiarrhythmic drugs such as sotalol and Kinidin, but also a variety of nonantiarrhythmic drugs, like certain antihistamines, antimicrobial drugs, psychiatric drugs, and cisapride, may induce prolongation of the Q-T interval and torsade de pointes . Special concern should be drawn to the co-administration of drugs that interfere with the metabolism and elimination of these drugs, such as ketoconazole . Patients with congenital long Q-T syndrome, patients with heart disease, with hypokalaemia or hypomagnesaemia, and women have an increased risk . Every sign on dizziness or syncope should be regarded as a warning sign of possible arrhythmia in patients treated with drugs that potentially prolong the Q-T interval . Measurement of the Q-T interval before and during treatment is generally recommended in high-risk patients.

Hong Kong Med J, 1997 Jun, 3(2), 179 - 185
Nucleic acid technology and infectious diseases; Wong SY et al.; The past decade has witnessed an explosion in the knowledge of microbial genetics, pathogenesis, and antimicrobial resistance as a result of advances in molecular technology . This has brought important breakthroughs in the management of patients with infectious diseases, as organisms that had previously been difficult to demonstrate in vitro can now be detected by molecular techniques such as the polymerase chain reaction . Not only is rapid diagnosis now possible, but old diseases of uncertain aetiology have been found to have an infective origin, for instance, Whipple's disease . Molecular technology has also contributed greatly to epidemiological studies of outbreaks, understanding antimicrobial resistance, developing new antimicrobial agents, the in vitro synthesis of immunomodulators, production of vaccines, and gene therapy . The limitations of these latest technologies, however, need to be remembered so that they yield meaningful information for patient care.

Antimicrob Agents Chemother, 2002 Mar, 46(3), 917 - 21
Intrapulmonary pharmacokinetics of telithromycin, a new ketolide, in healthy Japanese volunteers; Kadota J et al.; The concentrations of telithromycin, a new ketolide antimicrobial agent, in alveolar macrophages (AMs) and bronchoalveolar epithelial lining fluid (ELF) were determined in order to investigate the transfer of the drug into target tissue, relative to plasma, following multiple oral doses of telithromycin . Twenty-four healthy male Japanese volunteers were randomly allocated to four groups . Each subject was given 600 or 800 mg of telithromycin once daily for 5 days, followed by bronchoalveolar lavage (BAL) 2 or 8 h after the last dose (group A and B: 600 mg, 2 and 8 h BAL time point; group C and D: 800 mg, 2 and 8 h BAL time point) . The mean concentrations of the drug in AMs and ELF were 34.54 and 4.92 mg/liter in group A, 50.97 and 2.26 mg/liter in group B, 25.47 and 4.24 mg/liter in group C, and 108.22 and 4.31 mg/liter in group D, respectively, which markedly exceeded concentrations in plasma . These results demonstrated good transfer of telithromycin into AMs and ELF, suggesting good efficacy against common respiratory pathogens, including intracellular pathogens and atypical microorganisms.

Antimicrob Agents Chemother, 2002 Mar, 46(3), 755 - 61
Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells; Mealey KL et al.; P-glycoprotein (P-gp) overexpression by tumor cells imparts resistance to multiple antineoplastic chemotherapeutic agents (multiple drug resistance) . Treatment of tumor cells with chemotherapeutic agents such as anthracyclines, epipodophyllotoxins, and Vinca alkaloids results in induction of P-gp expression . This study was performed to determine if clinically relevant antimicrobial drugs (i.e., drugs that are used to treat bacterial infections in cancer patients) other than antineoplastic agents can induce expression of P-gp in MCF-7 breast carcinoma cells . Expression of P-gp and MDR1 mRNA was determined in samples from MCF-7 cells that were treated in culture with doxorubicin (positive control) and the antimicrobial drugs doxycycline, piperacillin, and cefoperazone . The functional status of P-gp was assessed using laser cytometry to determine intracellular doxorubicin concentrations . The MTT (3-{4,5-dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide) assay was used to determine if the cytotoxicity of experimental drugs was related to their ability to induce P-gp expression . MCF-7 cells treated with doxycycline (MCF-7/doxy) were stimulated to overexpress P-gp, whereas cells treated with piperacillin and cefoperazone did not overexpress P-gp . MCF-7/doxy cells were compared to a positive-control subline, MCF-7/Adr, previously selected for doxorubicin resistance, and to MCF-7 cells treated with doxorubicin (MCF-7/doxo) . All three sublines overexpressed P-gp and MDR1 mRNA and accumulated less intracellular doxorubicin than did control MCF-7 cells . P-gp expression was induced only by experimental drugs that were cytotoxic (doxorubicin and doxycycline) . Doxycycline, a drug that has been used for treatment of bacterial infections in cancer patients, can induce functional P-gp expression in cancer cells, resulting in multidrug resistance.

Int J Antimicrob Agents, 2002 Feb, 19(2), 155 - 8
Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxycillin and tetracycline in Lebanon; Sharara AI et al.; The aim of this study was to determine the prevalence of antimicrobial resistance amongst Helicobacter pylori isolates cultured from gastric biopsies taken during routine endoscopies at the American University of Beirut Medical Center in Lebanon . Fifty-four consecutively recovered H . pylori isolates were tested against metronidazole, clarithromycin, tetracycline and amoxycillin using the epsilometer test . Resistance to metronidazole (MIC > 8 mg/l) was found in 29.5% of the isolates while resistance to clarithromycin (MIC > or =0.25 mg/l) and tetracycline (MIC > or =4 mg/l) was low (4 and 2%, respectively) . All isolates were susceptible to amoxycillin (MIC < or =8 mg/l) . These findings are comparable with those reported from Europe and the United States . The prevalence of metronidazole resistance in our study was lower than that from other parts of the Middle East and the developing world.

Int J Antimicrob Agents, 2002 Feb, 19(2), 139 - 45
Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex; Tomioka H et al.; We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin, sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex (MAC) . Clarithromycin potentiated the activities of rifampicin and rifalazil against both extracellular and intramacrophage MAC . In contrast, all the test quinolones exhibited antagonistic effects against extracellular MAC when combined with either clarithromycin or rifamycins . Such an antagonism was not observed for the activity of these combinations against intramacrophage MAC . Combined effects were observed with combinations of these fluoroquinolones with either ethambutol or streptomycin . Similar profiles were seen for the activities of two-drug combinations of clarithromycin or fluoroquinolones with other drugs against intramacrophage MAC isolated from pulmonary and disseminated MAC infections.

Int J Antimicrob Agents, 2002 Feb, 19(2), 133 - 7
Induced expression of melittin, an antimicrobial peptide, inhibits infection by Chlamydia trachomatis and Mycoplasma hominis in a HeLa cell line; Lazarev VN et al.; As the number of pathogenic microbial strains resistant to different antibiotics increases, amphipathic peptides with antimicrobial activity are promising agents for the therapy of infectious diseases . This work deals with the effect of an amphipathic antimicrobial peptide, melittin, expressed within recombinant plasmid vectors, on infection with urogenital pathogens Chlamydia trachomatis and Mycoplasma hominis in HeLa cell culture . Recombinant plasmid constructs with the melittin gene under the control of the tetracycline-responsive promoter of human cytomegalovirus were obtained . We showed inhibition of C . trachomatis and M . hominis infection after the introduction of recombinant plasmid vectors expressing the melittin gene into the infected cell culture.

Cancer Lett, 2002 Apr 8, 178(1), 37 - 42
DNA damage induced by hypochlorite and hypobromite with reference to inflammation-associated carcinogenesis; Ohnishi S et al.; Hypohalites (OCl-, OBr-) are formed at inflammation sites as antimicrobial agents . OCl- is also used for the disinfection of water supplies and the association of drinking chlorinated water with cancer risk is pointed out . In this study, OCl- itself induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, while OBr- damaged DNA only when glutathione (GSH) was added . OCl- caused oxidative DNA damage more efficiently than OBr-/GSH . In experiment with 32P-labeled DNA fragments, OCl- strongly caused piperidine-labile sites at guanine residues than piperidine-inert 8-oxodG, whereas OBr-/GSH caused no piperidine-labile sites . Endogenous OCl- may play a role in genotoxicity close to the site of inflammation.

Mol Biochem Parasitol, 2002 Mar, 120(1), 53 - 60
Avian anticoccidial activity of a novel membrane-interactive peptide selected from phage display libraries; da Silva A Jr et al.; In the present work, we describe the discovery of PW2, a novel peptide presenting in vitro activity against Eimeria acervulina and E . tenella sporozoites . PW2 was selected from phage display (Ph.D.) peptide libraries by an alternative method of panning using living purified E . acervulina sporozoites as targets . Our results showed that the peptide disrupts the sporozoite pellicle, resembling the effect caused by most natural antimicrobial peptides . PW2 peptide was also effective against fungi and showed low activity against Toxoplasma gondii tachyzoites, but no activity against Trypanosoma cruzi, Crithidia fasciculata epimastigotes, and bacteria . Additionally, the parasiticidal concentrations of PW2 produced a very low lytic effect on mammalian and avian cells . The effectiveness against Eimeria sporozoites and the absence of adverse effects to host cells indicates that PW2 may be used as a model to generate new drugs for the control of avian coccidiosis.

Int J Parasitol, 2002 Apr, 32(4), 385 - 98
Pterin transport and metabolism in Leishmania and related trypanosomatid parasites; Ouellette M et al.; The folate metabolic pathway has been exploited successfully for the development of antimicrobial and antineoplasic agents . Inhibitors of this pathway, however, are not useful against Leishmania and other trypanosomatids . Work on the mechanism of methotrexate resistance in Leishmania has dramatically increased our understanding of folate and pterin metabolism in this organism . The metabolic and cellular functions of the reduced form of folates and pterins are beginning to be established and this work has led to several unexpected findings . Moreover, the currently ongoing sequencing efforts on trypanosomatid genomes are suggesting the presence of several gene products that are likely to require folates and pterins . A number of the properties of folate and pterin metabolism are unique suggesting that these pathways are valid and worthwhile targets for drug development.

Aliment Pharmacol Ther, 2002 Mar, 16 Suppl 1, 31 - 3
Review article: rabeprazole-based therapy in Helicobacter pylori eradication; Barth J et al.; Rabeprazole's favourable pharmacodynamic profile is a result of its rapid onset and its 24-h control of gastric parietal secretion . These qualities, and its antimicrobial properties, make it particularly effective in the treatment of Helicobacter pylori (H . pylori), which is a short course of treatment compared to other conditions treated with proton pump inhibitors . Recently completed trials in combination with amoxicillin, clarithromycin and metronidazole for 7 days achieved high eradication of H . pylori . An additional study assessing the efficacy of combined rabeprazole and antibiotic treatments of 3, 7, and 10 days' duration vs . FDA-approved 10-day omeprazole triple therapy is under way to address the possibility of shorter duration therapies in the USA.

Ann Intern Med, 2002 Feb 19, 136(4), 280 - 7
The stool antigen test for detection of Helicobacter pylori after eradication therapy; Vaira D et al.; BACKGROUND: Current noninvasive tests to confirm the eradication of Helicobacter pylori must be performed 4 weeks or more after eradication therapy is completed . OBJECTIVE: To determine whether the stool antigen test, a relatively new noninvasive test for H . pylori, administered at various times after eradication therapy correctly identifies persons with persistent H . pylori infection . DESIGN: Prospective blinded study . SETTING: Six clinical centers in the United States and Europe . PATIENTS: 84 H . pylori --infected patients undergoing endoscopy for upper abdominal symptoms . MEASUREMENTS: At baseline and on day 35 after the completion of triple eradication therapy, all patients underwent endoscopy with histologic examination, rapid urease test and culture, urea breath test, and a stool antigen test . The stool antigen test was also performed on days 3, 7, 15, 21, 28, and 35 after completion of therapy . RESULTS: Compared with the gold-standard endoscopic tests on day 35 after antimicrobial therapy, the urea breath test had a sensitivity of 94% (95% CI, 71% to 100%) and a specificity of 100% (CI, 94% to 100%) . The stool antigen test had a sensitivity of 94% (CI, 71% to 100%) and a specificity of 97% (CI, 89% to 100%) . On day 7 after treatment, the stool antigen test was predictive of eradication (positive predictive value, 100% {CI, 69% to 100%}; negative predictive value, 91% {CI, 82% to 97%}) . CONCLUSION: A positive result on the stool antigen test 7 days after completion of therapy identifies patients in whom eradication of H . pylori was unsuccessful.

Chem Pharm Bull (Tokyo), 2002 Feb, 50(2), 229 - 34
Photochemical behavior of sitafloxacin, fluoroquinolone antibiotic, in an aqueous solution; Araki T et al.; Sitafloxacin (STFX) hydrate, an antimicrobial agent, is photo-labile in aqueous solutions . The photodegradation rates (k) in neutral solutions were higher than those observed in acidic and alkaline solutions and maximum at the maximum absorption wavelength of STFX . The structures of photodegradation products were elucidated as 7-{7-amino-5-azaspiro{2.4}heptan-5-yl}-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and 1-(1-amino-2-{16-fluoro-1-(2-fluoro-1-cyclopropyl)-1,4-dihydro-4-oxo-3-quinolin-7-yl}-amino}ethyl)cyclopropanecarbaldehyde . This implies that dechlorination is the key step in the photodegradation of STFX . The effect of halide ions on the photodegradation of STFX was estimated by observing the increments in the photostability of STFX with the addition of chloride ions . In contrast, in the presence of bromide ions, instead of increased photostability of the STFX rate, a new photodegradation product in the presence of bromide ion was observed . The structure of this new photodegradation product was an 8-bromo form of STFX, which was substituted for chlorine at the 8-position, so the dissociation of C-Cl bond at the 8-position of STFX was the rate-limiting step in the initial process of the photodegradation . STFX generated .C (carbon centered radical) and .OH (hydroxyl radical) in the process of photodegradation in a pH 4.0 buffer . On the contrary, STFX did not generate C in the presence of chloride ion in a pH 4.0 buffer . The .C was generated and then degraded into the above degradation products by photoirradiation in the absence of chloride ion, but the .C immediately reacted with chloride when it was present . As a result, the C-Cl bond was recovered leading to a possible increase in the apparent photostability.

J Biol Chem, 2002 May 10, 277(19), 16941 - 51 Epub 2002 Feb 14.
Structural requirements for potent versus selective cytotoxicity for antimicrobial dermaseptin S4 derivatives; Kustanovich I et al.; To better understand the structural requirements for selective cytotoxicity of antimicrobial peptides, seven dermaseptin S4 analogs were produced and investigated with respect to molecular organization in solution, binding properties to model phospholipid membranes, and cytotoxic properties . Native dermaseptin S4 displayed high aggregation in solution and high binding affinity . These properties correlated with high cytotoxicity . Yet, potency was progressively limited when facing cells whose plasma membrane was surrounded by increasingly complex barriers . Increasing the positive charge of the native peptide led to partial depolymerization that correlated with higher binding affinity and with virtually non-discriminative high cytotoxicity against all cell types . The C-terminal hydrophobic domain was found responsible for binding to membranes but not for their disruption . Truncations of the C terminus combined with increased positive charge of the N-terminal domain resulted in short peptides having similar binding affinity as the parent compound but displaying selective activity against microbes with reduced toxicity toward human red blood cells . Nuclear magnetic resonance-derived three-dimensional structures of three active derivatives enabled the delineation of a common amphipathic structure with a clear separation of two lobes of positive and negative electrostatic potential surfaces . Whereas the spatial positive electrostatic potential extended considerably beyond the peptide dimensions and was required for potency, selectivity was affected primarily by hydrophobicity . The usefulness of this approach for the design of potent and/or selective cytolytic peptides is discussed herein.

J Clin Periodontol, 2002 Jan, 29(1), 1 - 8
Chlorhexidine varnishes: a review; Matthijs S et al.; BACKGROUND: Of all chemical plaque control agents, chlorhexidine digluconate has proven to be the most effective and safe . Since 1964, varnishes have been used for local delivery of fluor and are reported to be an effective and easy to use vehicle . During the past decade, varnishes for local delivery of antimicrobial agents have been developed and investigated in vitro and in vivo . AIM: In this paper, the existing literature on the use of 3 different chlorhexidine varnishes in different fields in dentistry is reviewed . METHOD: In vitro results concerning the release of the antimicrobial agents are compared for the 3 different varnish formulations . RESULTS AND CONCLUSION: Clinical reports on the efficacy of controlled-release systems in altering cariogenic and periodontopathic microflora are summarized.

Eur J Biochem, 2002 Feb, 269(3), 923 - 32
Antimicrobial dendrimeric peptides; Tam JP et al.; Dendrimeric peptides selective for microbial surfaces have been developed to achieve broad antimicrobial activity and low hemolytic activity to human erythrocytes . The dendrimeric core is an asymmetric lysine branching tethered with two to eight copies of a tetrapeptide (R4) or an octapeptide (R8) . The R4 tetrapeptide (RLYR) contains a putative microbial surface recognition BHHB motif (B = basic, H = hydrophobic amino acid) found in protegrins and tachyplesins whereas the octapeptide R8 (RLYRKVYG) consists of an R4 and a degenerated R4 repeat . Antimicrobial assays against 10 organisms in high- and low-salt conditions showed that the R4 and R8 monomers as well as their divalent dendrimers contain no to low activity . In contrast, the tetra- and octavalent R4 and R8 dendrimers are broadly active under either conditions, exhibiting relatively similar potency with minimal inhibition concentrations < 1 microm against both bacteria and fungi . Based on their size and charge similarities, the potency and activity spectrum of the tetravalent R4 dendrimer are comparable to protegrins and tachyplesins, a family of potent antimicrobials containing 17-19 residues . Compared with a series of linearly repeating R4 peptides, the R4 dendrimers show comparable antimicrobial potency, but are more aqueous soluble, more stable to proteolysis, less toxic to human cells and more easily synthesized chemically . These results suggest repeating peptides that cluster the charge and hydrophobic residues may represent a primitive form of microbial pattern-recognition . Incorporating such knowledge in a dendrimeric design therefore presents an attractive approach for developing novel peptide antibiotics.

Anal Biochem, 2002 Mar 1, 302(1), 70 - 4
Chemoenzymatic synthesis of peptidyl 3,4-dihydroxyphenylalanine for structure-activity relationships in marine invertebrate polypeptides; Taylor SW; An improved method for hydroxylating tyrosine-containing sequences in polypeptides to peptidyl 3,4-dihydroxyphenylalanine (DOPA) using mushroom tyrosinase at relatively high enzyme-to-substrate ratios is described . The new method involves incorporating borate into the reaction mixture to stop formation of the unwanted side product 3,4,5-trihydroxyphenylalanine . Using this method, a model for the palindromic central sequence for the antimicrobial peptide family, the styelins, Y*Y*KHKY*Y* (where Y* is DOPA), was successfully synthesized in high yield from YYKHKYY . This sequence represents a particularly challenging target because of the cluster of four precursor tyrosine residues are in close proximity . The method should be readily applied to larger polypeptides produced by either solid-phase synthesis or recombinant techniques and give greater insight into the roles of this unusual posttranslational modification in marine invertebrates such as mussels and ascidians.

J Periodontol, 2002 Jan, 73(1), 79 - 85
Inhibition of proteolytic, serpinolytic, and progelatinase-b activation activities of periodontopathogens by doxycycline and the non-antimicrobial chemically modified tetracycline derivatives; Grenier D et al.; BACKGROUND: Tetracyclines, particularly doxycycline (Doxy), and their non-antimicrobial chemically-modified derivatives (CMTs) inhibit the activities of human matrix metalloproteinases (MMPs), and reduce the severity and progression of periodontal disease in animal models and humans . In this study, the effects of Doxy and CMT-1, -3, and -5 on proteolytic, serpinolytic, and progelatinase-B activation activities of potent periodontopathogens were studied . METHODS: The effect of Doxy and CMTs (0.5 to 50 microM) on proteolytic activities were investigated by incubating bacteria with chromogenic substrates or human serum albumin . A collagenolytic fraction of Porphyromonas gingivalis was used to evaluate the effect of these substances on collagenolytic (type I collagen) and serpinolytic (alpha1-proteinase inhibitor) activities . Lastly, the effect of Doxy on progelatinase-B (pro-MMP-9) activation by purified proteinases from P . gingivalis and Treponema denticola was investigated by SDS-PAGE/Western immunoblotting . RESULTS: Doxy and CMTs, except CMT-5 which lacks the structural elements required for cation chelation, inhibited Arg- and Lys-gingipain activities as well as collagenolytic activity of P . gingivalis . Doxy and CMTs did not markedly affect the chymotrypsin-like activity of T . denticola but inhibited its trypsin-like activity . In addition, degradation of human serum albumin by cells of P . gingivalis and T . denticola was strongly inhibited by Doxy and CMT-1 . Doxy and CMT-1 also inhibited the inactivation of alpha1-proteinase inhibitor (serpinolytic activity) by a collagenolytic fraction of P . gingivalis . Lastly, Doxy prevented the latent to active conversion of human neutrophil progelatinase-B (pro-MMP-9) by Arg-gingipains A/B of P . gingivalis but not by the chymotrypsin-like proteinase of T . denticola . CONCLUSIONS: Data from this study suggest that Doxy and CMTs have the potential to inhibit the periodontopathogenic bacterial proteinases, which contribute to tissue destruction cascades during periodontitis directly and indirectly by triggering the host response.

Cell Mol Life Sci, 2002 Jan, 59(1), 156 - 70
The multifaceted Paneth cell; Porter EM et al.; Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkuhn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule-staining pattern . Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium . Since then, many constituents of the PC granules have been biochemically characterized . The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine . Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs . Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation.

Arch Otolaryngol Head Neck Surg, 2002 Feb, 128(2), 123 - 30
Physician specialty is associated with differences in the evaluation and management of acute bacterial rhinosinusitis; Werning JW et al.; BACKGROUND: Acute bacterial rhinosinusitis (ABRS) is a common illness that is routinely managed by physicians from several different specialties . However, the actual diagnostic and treatment preferences of physicians from these different specialties are not known . OBJECTIVE: To determine whether the radiographic evaluation and management of community-acquired ABRS differs according to medical specialty . DESIGN, SETTING, AND PARTICIPANTS: Randomized survey of 450 board-certified physicians in the United States from family medicine, general internal medicine, and otolaryngology . MAIN OUTCOME MEASURES: Responding physicians' use of diagnostic radiography as well as choice and duration of antimicrobial and adjunctive treatments of ABRS . RESULTS: Otolaryngologists were more likely to use supportive diagnostic radiography (P =.04) . They were also more likely to treat patients with adjunctive therapy, such as topical decongestants (P =.01), guaifenesin (P =.01), and saline nasal irrigation (P =.01), in addition to antibiotics . Otolaryngologists prescribed more medications to treat patients with ABRS than primary care physicians (P =.01) . There were no significant differences in diagnosis and management by family physicians and general internists . CONCLUSIONS: Otolaryngologists use more health care resources to diagnose and treat ABRS than primary care physicians despite an absence of evidence that such tests and treatments lead to better outcomes . Otolaryngologists typically treat a patient population with a higher prevalence of ABRS and frequently see referred patients with recurrent acute sinusitis and chronic rhinosinusitis, which may explain their tendency to treat patients more aggressively . Nevertheless, these survey results illustrate a lack of consensus within the medical community regarding the evaluation and management of community-acquired ABRS, suggesting that widely accepted evidence-based practice guidelines need to be developed.

Int J Food Microbiol, 2002 Jan 30, 72(1-2), 13 - 8
Reduction of the native microflora on alfalfa sprouts during propagation by addition of antimicrobial compounds to the irrigation water; Fett WF; Alfalfa and other types of sprouts are known to harbor large populations of native microorganisms . As some of these microbes may be causes of reduced shelf life of the product (plant pathogens and other spoilage organisms) and sprouts may, on occasion, harbor bacteria pathogenic towards humans, the addition of antimicrobial compounds to the irrigation water may be warranted . In this study, we tested the efficacy of several antimicrobial compounds for reducing the native microbial populations on alfalfa sprouts during propagation . These compounds included H2O2, peroxyacetic acid+hydrogen peroxide (Tsunami 100), acidified NaClO2, NaClO2 (Aquatize), EDTA, Na3PO4 and NaOCl . When added to the irrigation water at vanous concentrations, none of the antimicrobial compounds reduced the levels of any class of native microflora by more than 1 log10 without evidence of phytotoxicity.

Adv Dent Res, 2000 Dec, 14, 16 - 21
Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva; Edgerton M et al.; Non-immune salivary proteins--including lactoperoxidase, lysozyme, lactoferrin, and histatins--are key components of the innate host defense system in the oral cavity . Many antimicrobial proteins contain multiple functional domains, with the result that one protein may have more than one mechanism of antimicrobial activity . These domains may be separated by proteolytic cleavage, creating smaller proteins with functional antimicrobial activity in saliva as described for lysozyme, lactoferrin, and histatins . These small cationic proteins then exert cytotoxic activity to oral bacteria and fungi . Salivary histatin 5 initiates killing of C . albicans through binding to yeast membrane proteins and non-lytic release of cellular ATP . Extracellular ATP may then activate fungal ATP receptors to induce ultimate cell death . This mechanism for fungal cytotoxicity may be shared by other antimicrobial cationic proteins . Microbicidal domains of salivary and host innate proteins should be considered as potential therapeutic agents in the oral cavity.

Br J Nurs, 2001 Dec, 10(22 Suppl), S13 - 6, S18, S20
The use of honey in the treatment of infected wounds: case studies; Kingsley A; Honey is gaining popularity as a dressing for chronic wounds . Existing literature attributes honey with a number of useful properties, such as a broad-spectrum antimicrobial activity, deodorization, debriding and anti-inflammatory actions and stimulation of new tissue growth . Case studies are being published increasingly which record positive outcomes with its use . Recent national media attention has featured the beneficial effects of honey in wound care and patients are beginning to request treatment . While honey may become a useful and widely accepted product for wound management in the future, the following case studies demonstrate that not all the expected beneficial effects are always realized in practice.

Planta Med, 2002 Jan, 68(1), 66 - 7
Methyl psilalate: a new antimicrobial metabolite from Psila boliviensis; Erazo S et al.; Psila boliviensis (Wedd.) Cabr . yielded a new phenylpropanoid, named methyl psilalate . The structure was established by means of standard spectroscopic techniques . The microbiological evaluation of the compound revealed antibacterial activity against Gram-positive and Gram-negative bacteria.

Adv Ther, 2001 Nov-Dec, 18(6), 237 - 43
Potential antioxidant mechanism of action for metronidazole: implications for rosacea management; Miyachi Y; Chronic inflammation is believed to account for some symptoms of rosacea . The efficacy of topical metronidazole in the treatment of rosacea may be due to its antimicrobial as well as anti-inflammatory activity . Neutrophils release potent inflammatory mediators, including reactive oxygen species (ROS), and intrafollicular neutrophils have been observed in stage II disease . ROS and other free radicals may contribute to intrinsic and extrinsic aging, both of which accentuate clinical manifestations of rosacea . If, as in vitro data suggest, metronidazole has antioxidant activity, it may help subdue the oxidative tissue damage of intrinsic and extrinsic aging as well as prevent and treat rosacea symptoms.

Nat Prod Lett, 2001, 15(5), 315 - 22
A new biologically active triterpenoid saponin from the leaves of Lepidagathis hyalina Nees; Yadava RN; A new biologically active triterpenoid saponin m.f . C42H68O13, m.p . 315 degrees-317 degrees C was isolated from the ethyl acetate soluble fraction of the methanolic extract of the leaves of Lepidagathis hyalina . Its structure was characterized as 3-beta-O-{alpha-L-rhamnopyranosyl(1-->4)O-beta-D-glucopyranosyl}16-alpha-hydroxy-olean-12-en(13)-28-oic acid by several spectral and chemical analysis . This new triterpenoid saponin showed antimicrobial activity against various plants pathogenic bacteria and fungi.

Arch Biochem Biophys, 2002 Jan 15, 397(2), 342 - 4
The neutrophil NADPH oxidase; Babior BM et al.; The NADPH oxidase of phagocytes catalyzes the conversion of oxygen to O2(-) . This multicomponent enzyme complex contains five essential protein components, two in the membrane and three in the cytosol . Unassembled and inactive in resting phagocytes, the oxidase becomes active after translocation of cytosolic components to the membrane to assemble a functional oxidase . Multiple factors regulate its assembly and activity, thus serving to maintain this highly reactive system under spatial and temporal control until recruited for antimicrobial or proinflammatory events . The recent identification of homologs of one of the membrane components in nonphagocytic cells will expand understanding of the biological contexts in which this system may function . (c)2002 Elsevier Science.

Pediatr Infect Dis J, 2002 Feb, 21(2), 141 - 7
Six year multicenter surveillance of invasive pneumococcal infections in children; Kaplan SL et al.; OBJECTIVE: Monitor clinical and microbiologic features including antimicrobial susceptibility of invasive pneumococcal infections among children . DESIGN: A 6-year (September, 1993, through August, 1999) prospective surveillance study of all invasive pneumococcal infections in children . PATIENTS: Infants and children cared for at eight children's hospitals in the United States with culture-proved invasive pneumococcal infection . RESULTS: During the 6-year period 2581 episodes of invasive pneumococcal infection occurred in 2498 children . Underlying conditions were present in 29% of the children . Of children without an underlying condition, 15% of the total infections occurred in those 25 to 60 months old . As the ages of the children advanced the proportion of cases classified as bacteremia declined, whereas the proportion classified as pneumonia increased . Also, as the ages of the children increased the proportion of isolates in serotypes/serogroups 1, 3 and 23 increased . whereas the proportion for serotype 14 diminished . During the 6 years of the study, there was a significant increase in the percentage of isolates intermediate or resistant to penicillin (P < 0.000001) or intermediate to ceftriaxone (P < 0.002) . By the sixth year of the study, 37 and 11% of the isolates were nonsusceptible to penicillin or ceftriaxone, respectively . Antibiotic use in the 30 days before diagnosis of systemic pneumococcal infection occurred in 30 to 35% of the children for each of the 6 years . The overall case-fatality rate for children with systemic pneumococcal infection was 1.56% . Mortality was greatest in children >60 months old and in those with underlying conditions; mortality was not related to antibiotic susceptibility . CONCLUSIONS: The percentage of pneumococcal isolates recovered from children with systemic infection which were intermediate for penicillin or ceftriaxone or resistant to penicillin increased steadily during the 6-year period . There was also a trend toward increasing rates of resistance to ceftriaxone . The age and serogroup/serotype distributions of our patients support the recommendations to consider administration of the seven valent pneumococcal conjugate vaccine for all children 24 to 59 months old, with special consideration for selected groups.

Crit Care Med, 2002 Jan, 30(1 Supp), S58 - S63
Interleukin-10: A complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug; Oberholzer A et al.; Interleukin (IL)-10 is a pleiotropic cytokine produced by both T cells and macrophages and possesses both anti-inflammatory and immunosuppressive properties . IL-10 circulates in the blood of patients with sepsis syndromes, and increased concentrations of IL-10 have been associated with an adverse clinical outcome . Experimental studies in rodents and primates have demonstrated that endogenously produced and exogenously administered IL-10 can reduce the magnitude of the inflammatory response and improve outcome, primarily in models of endotoxemic and bacteremic shock . However, endogenous IL-10 production and systemic administration can also exacerbate T-cell dysfunction, decrease T-cell apoptosis, reduce antimicrobial function, and increase mortality in other less acute bacterial models of sepsis or after thermal injury . Targeted delivery of IL-10 to individual tissues may obviate the adverse effects of systemic delivery . The potential anti-inflammatory properties of IL-10 will have to be carefully weighed against its immunosuppressive properties when considering its use in patients with acute inflammation and sepsis syndromes.

Gut, 2002 Mar, 50(3), 285 - 9
Molecular testing for antibiotic resistance in Helicobacter pylori; Owen RJ; An estimated 7.5 million individuals in England and Wales are actively infected with Helicobacter pylori and hence knowledge of local resistance rates is of growing importance . Also, information on strain resistance following treatment failure is crucial in selecting an appropriate regimen as the development of bacterial resistance to antibiotics makes retreatment difficult . Molecular test methods may have an impact on improving the availability and accuracy of information on H pylori antimicrobial resistance to guide in the selection of primary as well as secondary backup treatment regimens.

Pest Manag Sci, 2002 Jan, 58(1), 33 - 7
Antimicrobial and pesticidal activity of partially purified flavonoids of Annona squamosa; Kotkar HM et al.; Foliar extracts of Annona squamosa (Family: Annonaceae) were screened for antimicrobial and insecticidal activity against the common microbial infestants of pulses and the stored grain pest pulse beetle, Callosobruchus chinensis (Coleoptera: Bruchidae) . Flavonoids isolated from aqueous extracts of A squamosa showed antimicrobial activity against all the common microbial contaminants of pulses and 80% insecticidal activity against C chinensis at a concentration of 0.07 mg ml-1 . Various physico-chemical tests, chromatographic and spectroscopic studies with partially purified aqueous extract indicated the presence of flavonol type flavonoids . This may provide a useful beginning for the development of botanical pesticides for post-harvest safeguard of pulses.

Arzneimittelforschung, 2002, 52(1), 45 - 52
Effects on Mycobacterium avium replication in normal human macrophages by deferiprone (L1) and other iron chelators . Possible implications on toxicity; Douvas GS et al.; Mycobacterium avium growth in cultured human macrophages is influenced by serum lipids, transferrin and iron levels . Iron-saturated transferrin enhances M . avium growth, whereas apotransferrin inhibits mycobacterial replication . The ability of iron chelators to mimic the effects of transferrin on intracellular and extracellular M . avium growth was examined . Smooth, transparent, AIDS patient derived M . avium 7497 scrovar 4 was used to infect 7-day cultured human macrophages . Growth was measured by determining the colony-forming units (CFU) after infected macrophages were lysed 0 to 7 days after infection . The new iron chelating drug deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one or L1, CAS 30652-11-0), 1-ethyl-2-methyl-3-hydroxypyrid-4-one (L1NEt), 1-propyl-2-methyl-3-hydroxypyrid-4-one (L1NPr), 1-allyl-2-methyl-3-hyproxypyrid-4-one (L1NAll), and 3,4-dihydroxycinnamic acid enhanced intracellular and extracellular mycobacterial replication at concentrations of 0.1-2.5 micrograms/ml . 2-Pyridinecarboxaldehyde-2-quinolylhydrazone (PCQH) inhibited intracellular replication from 0.1-1.0 microgram/ml . Most, but not all of the PCQH-induced intracellular inhibition could be eliminated using iron at concentrations greater than 1.0 microgram/ml . Iron also suppressed the effects of PCQH on extracellular M . avium replication . These results indicate that iron chelators may have variable effects at different concentrations and can significantly alter both intracellular and extracellular M . avium replication . It is suggested that at low concentrations deferiprone and other aketohydroxypyridine chelators could enhance the growth of M . avium but at high concentrations may function as adjunct therapy with other antimicrobials against infections with M . avium . These findings are important for therapeutic considerations and dose protocol design in relation to the new iron chelating drug deferiprone, which is currently used in thalassaemia and other iron loaded patients, some of whom are suffering from AIDS.

Arzneimittelforschung, 2002, 52(1), 39 - 44
Synthesis of some new diaryl and triaryl hydrazone derivatives as possible estrogen receptor modulators; Pandey J et al.; 1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and 1-naphthyl-1-(4-substituted phenyl)-methanone (2,4-dinitrophenyl)hydrazones have been synthesized and evaluated for their anti-implantation, uterotrophic, antiuterotrophic, anticancer and antimicrobial activities . Diphenolic hydrazone (compound 6) showed maximum uterotrophic inhibition of 70%, whereas compound 20 exhibited cytotoxicity in the range of 50-70% against MCF-7 and ZR-75-1 human malignant breast cell lines.

Shock, 2002 Feb, 17(2), 135 - 8
Bioglass attenuates a proinflammatory response in mouse peritoneal endotoxicosis; Rectenwald JE et al.; Bioglass is a bioactive, resorbable ceramic particle that was developed to assure binding to living tissues . Bioglass is currently employed to fill osseus defects in oral surgery, and it possesses both unique anti-inflammatory and antimicrobial properties . In an effort to determine whether Bioglass may be useful as an adjunct anti-inflammatory device in local inflammatory processes, we examined whether exposure of the peritoneal cavity to Bioglass would induce a pro- or anti-inflammatory response, and then modulate a subsequent proinflammatory response to endotoxin . Three- to fifty-milligram doses of 5 pm Bioglass were administered intraperitoneally in C57BL/6 mice . Total leukocyte, myeloperoxidase, and cytokine levels in the peritoneal wash fluid were determined . In addition, the peritoneal cavity was preexposed to Bioglass, and was then subjected to a subsequent endotoxin administration . All doses of Bioglass were found to induce a significant peritoneal IL-6 response; however, Bioglass did not induce a TNF-alpha, IL-1alpha, IL-10, or a white cell recruitment into the peritoneal lavage fluid . Pretreatment of the peritoneal cavity with Bioglass produced a transient reduction in the proinflammatory response to endotoxin . We conclude that exposure to Bioglass produces an IL-6 response without concurrent expression of TNF-alpha or IL-1alpha . Bioglass appears to transiently suppress the inflammatory response to endotoxin, possibly through the early induction of IL-6 . These findings suggest that Bioglass may offer a unique approach in modifying the inflammatory response in local tissue compartments.

Z Naturforsch {C}, 2001 Nov-Dec, 56(11-12), 979 - 82
Chemical analysis and antimicrobial activity of Halimium voldii; Demetzos C et al.; Volatile constituents and a hexane extract of the leaves of Halimium voldii Kit Tan, Perdetzoglou & Raus, sp . nova, were analyzed by GC and GC-MS . Thirty compounds were identified in the essential oil of Halimium representing 88.7% of the oil composition . The main components were nonanal (12.8%), dodecane (10.6%), Z-caryophyllene (8.2%), gamma-muurolene (10.9%), delta-cadidene (3.5%), caryophyllene oxide (5.1%), beta-eudesmol (3.6%) and manoyl oxide (5.5%) . Thymol was identified in the hexane extract as the main compound . A labdane diterpene ent-labd-7, 13 (E)-dien, 15-ol was detected by its mass spectra fragmentation pattern and its structure was determined by spectroscopic methods and its optical rotation . The essential oil and the hexane extract were assayed for their antimicrobial activity against gram (+) and gram (-) bacteria.

Pharmacotherapy, 2002 Feb, 22(2 Pt 2), 63S - 70S
Cost perspectives for outpatient intravenous antimicrobial therapy; Tice AD et al.; Intravenous antimicrobial therapy often continues after a patient is discharged from the hospital or it begins in the outpatient setting . Reimbursement for this therapy varies by payer . The United States Outpatient Parenteral Antibiotic Therapy (OPAT) Outcomes Registry is a valuable resource for quantifying cost by payer, as well as for describing practice patterns and adverse events related to intravenous antimicrobial therapy . To describe the reimbursement structure and cost of intravenous vancomycin home care therapy for four different types of payers, a survey of home infusion companies was done . Also surveyed were infusion programs participating in the OPAT Outcomes Registry, representing four different types of payers, to determine the cost of outpatient intravenous therapy . A retrospective cohort study of these infusion programs was conducted to describe practice patterns and to identify adverse events that resulted from intravenous vancomycin . We found that the cost of outpatient therapy was substantial, although nonuniform, across payer types . Alternative outpatient therapies associated with lower risks for adverse events and lower costs should be considered.

Pharmacotherapy, 2002 Feb, 22(2 Pt 2), 55S - 62S
Use of insurance claims data to assess outpatient antimicrobial therapy for gram-positive infections; Carmeli Y et al.; With the increasing frequency of antibiotic-resistant gram-positive infections in the United States, many patients are being treated outside the hospital setting . The majority of studies on the cost of outpatient antimicrobial therapy involve retrospective medical record review or prospective data collection . These methods tend to be expensive and time consuming, and often fail to produce a sufficiently large sample size . Analysis of insurance claims data offers a convenient approach for studying the costs associated with outpatient therapy for gram-positive infections . To demonstrate this approach, a study of the cost of intravenous vancomycin home care therapy was conducted using claims data from a large insurance company.

Photochem Photobiol, 2002 Jan, 75(1), 51 - 7
Rapid control of wound infections by targeted photodynamic therapy monitored by in vivo bioluminescence imaging; Hamblin MR et al.; The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies . In this study we report on the first use of a photochemical approach to destroy bacteria infecting a wound in an animal model . Following topical application, a targeted polycationic photosensitizer conjugate between poly-L-lysine and chlorin(e6) penetrated the gram (-) outer bacterial membrane, and subsequent activation with 660 nm laser light rapidly killed Escherichia coli infecting excisional wounds in mice . To facilitate real-time monitoring of infection, we used bacteria that expressed the lux operon from Photorhabdus luminescens; these cells emitted a bioluminescent signal that allowed the infection to be rapidly quantified, using a low-light imaging system . There was a light-dose dependent loss of luminescence in the wound treated with conjugate and light, not seen in untreated wounds . Treated wounds healed as well as control wounds, showing that the photodynamic treatment did not damage the host tissue . Our study points to the possible use of this methodology in the rapid control of wounds and other localized infections.

Int J Syst Evol Microbiol, 2002 Jan, 52(Pt 1), 235 - 40
Pseudoalteromonas ruthenica sp . nov., isolated from marine invertebrates; Ivanova EP et al.; On the basis of phenotypic and genotypic characteristics and analysis of 165 rRNA sequences, a novel species belonging to the genus Pseudoalteromonas is described . Two pale-orange-pigmented strains, KMM 300T and KMM 290, isolated respectively from a mussel, Crenomytilus grayanus, and a scallop, Patinopecten yessoensis, are marine, gram-negative, aerobic, rod-shaped bacteria that produce a number of antimicrobial compounds . The strains are able to degrade gelatin, elastin, starch, DNA and Tween 80 . Chitin and agar are not degraded . The isolates from marine invertebrates grew at NaCl concentrations of 1-9% and a temperature range of 10-35 degrees C and did not utilize most of the wide range of carbohydrates tested, with the exception of D-glucose, cellobiose and sucrose . The DNA G+C content was 48.4-48.9 mol% . The level of DNA homology of the two strains was 98% . DNA from the strains isolated from marine invertebrates showed 5-15% genetic relatedness to the DNA of other type strains of the genus Pseudoalteromonas . 16S rRNA analysis indicated a clear affiliation of the novel bacteria to other species of the genus . The strains are assigned to a novel species, Pseudomonas ruthenica sp . nov., with the type strain KMM 300T (= LMG 19699T = CIP 106857T).

Bioorg Med Chem, 2002 Apr, 10(4), 855 - 67
Histidine kinases as targets for new antimicrobial agents; Matsushita M et al.; The emergence and spread of hospital acquired multi drug resistant bacteria present a need for new antibiotics with innovative mode of action . Advances in molecular microbiology and genomics have led to the identification of numerous bacterial genes coding for proteins that could potentially serve as targets for antibacterial compounds . Histidine kinase promoted two-component systems are extremely common in bacteria and play an important role in essential signal transduction for adapting to bacterial stress . Since signal transduction in mammals occurs by a different mechanism, inhibition of histidine kinases could be a potential target for antimicrobial agents . This review will summarize our current knowledge of the structure and function of histidine kinase and the development of antibiotics with a new mode of action: targeting histidine kinase promoted signal transduction and its subsequent regulation of gene expression system.

Peptides, 2002 Mar, 23(3), 427 - 35
Antimicrobial peptides from skin secretions of Chinese red belly toad Bombina maxima; Lai R et al.; Two groups of antimicrobial peptides have been isolated from skin secretions of Bombina maxima . Peptides in the first group, named maximins 1, 2, 3, 4 and 5, are structurally related to bombinin-like peptides (BLPs) . Unlike BLPs, sequence variations in maximins occurred all through the molecules . In addition to the potent antimicrobial activity, cytotoxicity against tumor cells and spermicidal action of maximins, maximin 3 possessed a significant anti-HIV activity . Maximins 1 and 3 were toxic to mice with LD(50) values of 8.2 and 4.3 mg/kg, respectively . Peptides in the second group, termed maximins H1, H2, H3 and H4, are homologous with bombinin H peptides . cDNA sequences revealed that one maximin peptide plus one maximin H peptide derived from a common larger protein.

Chest, 2002 Feb, 121(2), 652 - 4
Septic pulmonary embolism associated with periodontal disease: reports of two cases and review of the literature; Shiota Y et al.; We report two cases of septic pulmonary embolism associated with periodontitis . Chest CT revealed multiple nodular shadows with features characteristic of septic pulmonary embolism in both patients . Both patients had toothache, fever, and chest pain, and showed findings of periodontitis at initial presentation . Antimicrobial agents combined with dental surgery were successful in treatment . While septic pulmonary embolism from the lesions of periodontitis appears to be rare, periodontitis remains important in the differential diagnosis of septic pulmonary embolism.

Contraception, 2001 Dec, 64(6), 383 - 91
Single and multiple exposure tolerance study of cellulose sulfate gel: a Phase I safety and colposcopy study; Mauck C et al.; Vaginally applied gels offer a promising approach for preventing unwanted pregnancies and sexually transmitted infections . Cellulose sulfate (CS) is a non-cytotoxic antifertility agent that also exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV . This was a randomized, double-blinded, Phase I study of 2.5 mL and 5.0 mL doses of 6% CS gel . A single vaginal application of the gel followed by five consecutive daily doses was assessed for genital irritation, safety, vaginal leakage, and product acceptability compared to two controls, Conceptrol, which is a marketed contraceptive gel containing nonoxynol-9, and K-Y jelly . The results suggest that the safety of 6% CS was comparable to that of Conceptrol and K-Y jelly, and it may be associated with less genital irritation . The 2.5 mL dose of CS may be preferable according to the participants' reports of leakage . All the products had similar acceptability profiles.

J Urol, 2002 Mar, 167(3), 1210 - 7
Mycoplasma genitalium: another important pathogen of nongonococcal urethritis; Deguchi T et al.; PURPOSE: We reviewed findings on the pathogenic role of Mycoplasma genitalium in nongonococcal urethritis and the treatment of men with M . genitalium positive nongonococcal urethritis . MATERIALS AND METHODS: We reviewed literature selected from peer reviewed journals listed in MEDLINE and from resources cited in those articles from 1967 to January 2001 . RESULTS: M . genitalium was first isolated from 2 men with nongonococcal urethritis and thereafter it was shown to cause urethritis in subhuman primates inoculated intraurethrally . This mycoplasma has been detected significantly more often in patients with acute nongonococcal urethritis, particularly in those with nonchlamydial nongonococcal urethritis, than in those without urethritis . The prevalence of M . genitalium positive nonchlamydial nongonococcal urethritis is 18.4% to 45.5% of all nonchlamydial nongonococcal urethritis cases . In addition, the persistence of M . genitalium in the urethra after antimicrobial chemotherapy is associated with persistent or recurrent nongonococcal urethritis . M . genitalium is highly susceptible to tetracycline, macrolide and some new fluoroquinolones . The regimen of 100 mg . doxycycline orally twice daily for 7 days, which is recommended for chlamydial nongonococcal urethritis, seems to be effective for M . genitalium positive nongonococcal urethritis, although clinical data to substantiate this regimen are limited . CONCLUSIONS: The various results reported to date tend to support the proposition that M . genitalium is a pathogen of nongonococcal urethritis . However, currently diagnostic methods for this important mycoplasma are not available in clinical practice . Because of the possible association of the posttreatment presence of M . genitalium in the urethra with persistent or recurrent nongonococcal urethritis, eradication of this mycoplasma from the urethra is essential for managing M . genitalium positive disease . However, clinical data on treating M . genitalium positive nongonococcal urethritis are extremely limited . Thus, further studies are required to develop new diagnostic methods that would be available in clinical settings and establish a new treatment algorithm for nongonococcal urethritis, including M . genitalium positive disease.

J Postgrad Med, 2001 Apr-Jun, 47(2), 95 - 9
Cutaneous adverse drug reactions: clinical pattern and causative agents--a 6 year series from Chandigarh, India; Sharma VK et al.; AIM: To study the different clinical spectrum of cutaneous adverse drug reactions (ADR) and to determine the causative drugs . MATERIALS & METHODS: A prospective, hospital based study was carried out over a period of 6 years recording various cutaneous ADR . RESULTS: A total of 500 patients with cutaneous ADR were enrolled in the study . The most common types of cutaneous ADR patterns were maculopapular rash (34.6%), fixed drug eruption (FDE) (30%) and urticaria (14%) . The drugs most often incriminated for the various cutaneous ADR were antimicrobials (42.6%), anticonvulsants (22.2%) and NSAIDs (18%) . Anticonvulsants were implicated in 41.6% of maculopapular rashes . Sulfonamides accounted for 43.3% and NSAIDs for 30.7% of FDE . Urticaria was caused mainly by NSAIDs(24.3%) and penicillins(20%) . Anticonvulsants were responsible for 43.8% of life-threatening toxic epidermal necrolysis and Stevens Johnson syndrome . CONCLUSIONS: The clinical pattern and drugs causing cutaneous ADR are similar to those observed in other countries except for minor variations . Cutaneous ADR patterns and the drugs causing various reactions are changing every year, which may be due to the emergence of newer molecules and changing trends in the use of drugs.

Hong Kong Med J, 1998 Mar, 4(1), 7 - 10
The combination of omeprazole, amoxycillin, and clarithromycin eradicates Helicobacter pylori in 95% of patients---7 days of therapy is as good as 10 days; Ching CK et al.; More than half of the known Helicobacter pylori strains are resistant to metronidazole, according to previous Hong Kong studies . The response rates to treatment regimens that comprise metronidazole as one of the antimicrobial agents have usually been disappointing in cases involving metronidazole-resistant strains . The objective of this open cohort evaluation was to assess the efficacy of an alternative regimen that combines omeprazole with amoxycillin and clarithromycin in Helicobacter pylor-positive ulcer and non-ulcer patients in Hong Kong . Furthermore, we aimed to investigate if 7 days were as good as 10 days of therapy . We studied 186 Helicobacter pylor-positive subjects; 149 subjects received 7 days of combination therapy and 37 subjects received 10 days . Our results showed that the overall Helicobacter pylori eradication efficiency was identical (94.6%) for both treatments . The incidences of adverse effects were also very similar (16.8% versus 16.2%) and both treatments were well tolerated . Thus, we propose that omeprazole in combination with amoxycillin and clarithromycin should be considered as one of the first-line therapies for patients with Helicobacter pylor infection in Hong Kong.

Am J Physiol Endocrinol Metab, 2002 Mar, 282(3), E650 - 6
COX-2 inhibition attenuates anorexia during systemic inflammation without impairing cytokine production; Johnson PM et al.; Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination . Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease . Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS) . Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss . Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration . Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.

Ned Tijdschr Tandheelkd, 1994 Jan, 101(1), 10 - 4; quiz 15, 22
{Halitosis (fetor ex ore) . A review}; van Nieuw Amerongen A et al.; About 15% of the Dutch population has, in a more or lesser degree, complaints about bad breath . This is caused particularly by the anaerobic metabolism of a number of oral microorganisms, in which putrefaction occurs and volatile sulfur compounds will be formed . Some of these compounds are also possibly involved in the pathogenesis of periodontitis . A good oral hygiene is of primary importance to prevent halitosis and to reduce bad breath . Antiseptic mouth-waters can be helpful in the reduction of the bacterial metabolism . In addition, stimulation of the salivary secretion has a dual favourable effect, firstly because of its antimicrobial salivary proteins, and secondly by reduction of the retention of nutrients in the oral cavity.

Biochem Biophys Res Commun, 2002 Feb 15, 291(1), 17 - 22
Genetic variants of human beta-defensin-1 and chronic obstructive pulmonary disease; Matsushita I et al.; Chronic obstructive pulmonary disease (COPD) is due to interactions between cigarette smoke exposure and other risk factors . Genetic variations of human beta-defensin-1 (hBD-1), an endogenous antimicrobial peptide in the airway, were investigated in 60 patients and 213 healthy volunteers by single-strand conformation and restriction fragment length polymorphism analysis and DNA sequencing . Four nucleotide variations in the 5' and 3' untranslated regions and two nonsynonymous substitutions in the coding region were identified . Of these, a newly found Ile38 variant was observed in 15.0% of patients but only in 2.8% of healthy individuals and was significantly associated with the disease (OR = 6.1, 95% confidence intervals 2.0-8.3, P = 0.0012) . More than 80% of those with Ile38 experienced sputum production for more than 3 months during the follow-up period . Genetic variations in hBD-1 may define a high-risk subgroup of COPD where the component of chronic bronchitis is predominant . (c)2002 Elsevier Science (USA).

Farmaco, 2001 Dec, 56(12), 965 - 73
Synthesis and antimicrobial activities of novel naphtho{2,1-b}pyran, pyrano{2,3-d}pyrimidine and pyrano{3,2-e}{1,2,4}triazolo{2,3-c}-pyrimidine derivatives; Bedair AH et al.; The synthesis of new naphtho{1',2':5,6}pyrano{2,3-d}pyrimidines and related heterocycles has been reported . The key intermediate 3-amino-8-bromo-1-(p-methoxyphenyl)-1H-naphtho{2,1-b} pyran-2-carbonitrile (3c) was obtained in one pot synthesis by treating alpha-cyanocinnamonitrile (1c) with 6-bromo-2-naphthol (2) . Antimicrobial activity was shown for some of the synthesized compounds.

Farmaco, 2001 Dec, 56(12), 953 - 8
Synthesis and structure elucidation of some new thioether derivatives of 1,2,4-triazoline-3-thiones and their antimicrobial activities; Gulerman NN et al.; 5-(4-Pyridinyl)-4-substituted-2.4-dihydro-3H-1,2,4-triazole-3-thiones and 5-(4-pyridinyl)-4-substituted-3-(benzoylmethyl)thio-4H-1,2,4-triazoles were synthesized . The structures of original nine compounds were confirmed by IR, 'H NMR, mass spectral methods and elemental analysis . The antibacterial, antifungal and antimycobacterial activities, together with those of known intermediate 1,4-disubstituted thiosemicarbazides, were reported.

Farmaco, 2001 Dec, 56(12), 933 - 8
Novel functionalized pyrido{2,3-g}quinoxalinones as antibacterial, antifungal and anticancer agents; Carta A et al.; A series of twelve novel pyrido{2,3-g}quinoxalinones (3-14), variously substituted at the C-3 position, was synthesized, structurally determined and submitted to a preliminary in vitro evaluation for antibacterial, anticandida and anticancer activities . Results of the antimicrobial screening showed that all compounds, with the exception of 6, 11 and 12, exhibited interesting activity against all strains tested; while compound 10 was found to have encouraging in vitro anticancer activity at a concentration of l0(-4) M.

Pharmacoepidemiol Drug Saf, 2001 Oct-Nov, 10(6), 487 - 92
Construction of the Korea Elderly Pharmacoepidemiologic Cohort: drug utilization review of cephalosporins in geriatric inpatients; Park BJ et al.; We performed a cohort-based pharmacoepidemiologic study in order to evaluate the pattern of cephalosporin prescriptions in elderly inpatients in Korea . The Korea Elderly Pharmacoepidemiologic Cohort was composed of a geriatric population of beneficiaries of the Korea Medical Insurance Corporation residing in Busan in 1993 . The cohort consisted of 23,649 members, comprising 15,221 women (64.4%) and 8428 men (35.6%) . The study population for drug utilization review consisted of those cohort members who were admitted into hospitals during the period January 1993 through December 1994 . The number of hospitalized patients was 4262, comprising 2631 women (61.7%) and 1681 men (38.3%) . The trend of cephalosporin prescriptions over the 2-year period showed that the use of second and third generation cephalosporins increased relative to the use of first generation . The use of cephalosporins combined with other antibiotics was found to occur in 22.8% aminoglycosides (76.7%) and quinolones (17.1%) being the most common antibiotics combined with cephalosporins . Our result demonstrates an increase in the prescription of second and third generation cephalosporins in Korea, which has implications not only for the elderly population but also for the total population because of the impact on health care costs and the potential for the emergence of antimicrobial resistance.

Nippon Geka Gakkai Zasshi, 2001 Dec, 102(12), 860 - 5
{Antibiotic management guidelines in trauma and critical care}; Ikeda H et al.; Many patients with severe illness or conditions like multiple trauma and severe burns are vulnerable to infection due to their depressed immune function . In addition, most patients in the intensive care unit are at increased risk of developing ventilator-associated pneumonia and catheter-related sepsis . A basic concept of antibiotic use in these guidelines is to diagnose infection and identify the pathogenic microorganism as soon as possible . We should not start inadequate empirical antimicrobial therapy in cases of undetermined infection focus or pathogen because it may increase the risk of development of antibiotic-resistant bacteria and opportunistic infections . Antibiotic use should be planned deliberately from the time of admission in patients hospitalized long time . Prophylactic antibiotic use should be restricted to a specific diagnosis or an exceptional condition . The antibiotic choice should be determined based on data on antibiotic-resistant bacteria in the ward of a trauma center.

Nippon Geka Gakkai Zasshi, 2001 Dec, 102(12), 842 - 5
{Guideline of antimicrobial therapy in the area of cardiovascular surgery}; Matsuda H et al.; Although cardiovascular surgery is considered to be aseptic, prolonged hospital stay before and after surgery, the use of artificial materials and cardiopulmonary bypass, long-term use of intratracheal tubes or intravenous catheters, and an increase in surgeries on high-risk patients increase the incidence of postoperative infections . Therefore meticulous management to minimize bacterial contamination before and after surgery and identification of patient risk factors are important to reduce their incidence and severity, in addition to optimal antimicrobial therapy . As the targets of prophylactic antibiotics are usually superficial and environmental bacteria, those of choice are first or second-generation cephalosporins or penicillin with sulbactam . If postoperative infection is suspected, identification of the infectious site and pathogens and their susceptibility to anitimicrobials is useful to control infections . The use of broad-spectrum antibiotics is not recommended because these drugs induce bacterial resistance to antibiotics . Infectious endocarditis (IE) and deep wound infections, such as mediastinitis, are major serious infections after cardiovascular surgery . Antibiotics should be selected by considering the susceptibility of pathogens and pharmacokinetic properties of antibiotics, such as concentration in infected tissue . In patients reluctant to medical therapies, surgical intervention such as valve repair or replacement in IE and debridement and omental flap in mediastinitis should be considered.

Chembiochem, 2001 Aug 3, 2(7-8), 559 - 69
Novel dications with unfused aromatic systems: trithiophene and trifuran derivatives of furimidazoline; Bilik P et al.; We report the synthesis, interaction with DNA, topoisomerase II inhibition, and cytotoxicity of two novel unfused aromatic dications derived from the antimicrobial agent furimidazoline . The central diphenylfuran core of furimidazoline has been replaced with a trithiophene (DB358) or a trifuran (DB669) unit and the terminal imidazoline groups were preserved . The strength and mode of binding of the drugs to nucleic acids were investigated by complementary spectroscopic techniques including spectrophotometric, surface plasmon resonance, circular and linear dichroism measurements . The trifuran derivative forms intercalation complexes with double-stranded DNA, whereas the mode of binding of the trithiophene derivative varies depending on the drug/DNA ratio, as independently confirmed by NMR spectroscopic studies performed with (A-T)7 and (G-C)7 oligomers . Two-dimensional NMR data provided a molecular model for the binding of DB358 within the minor groove of the AATT sequence of the decanucleotide d(GCGAATTCGC)(2) . DNase I footprinting experiments confirmed the sequence-dependent binding of DB358 to DNA . The trithiophene derivative interacts preferentially with AT-rich sequences at low concentrations, but can accomodate GC sites at higher concentrations . DNA relaxation assays revealed that DB358 stimulated DNA cleavage by topoisomerase II, in contrast to DB669 . The substitution of N-alkylamidines for the imidazoline terminal groups abolished the capacity of the drug to poison topoisomerase II . At the cellular level, flow cytometry analysis indicated that DB358, which is about six times more cytotoxic than the trifuran analogue, induced a significant accumulation of HL-60 human leukemia cells in the G2/M phase . The incorporation of thiophene heterocycles appears as a convenient procedure to limit the strict AT selectivity of dications containing an extended unfused aromatic system and to design cytotoxic DNA intercalating agents acting as poisons for human topoisomerase II.

Chembiochem, 2001 Aug 3, 2(7-8), 494 - 504
Fatty acid hydroperoxide lyase: a plant cytochrome p450 enzyme involved in wound healing and pest resistance; Noordermeer MA et al.; Plants continuously have to defend themselves against life-threatening events such as drought, mechanical damage, temperature stress, and potential pathogens . Nowadays, more and more similarities between the defense mechanism of plants and that of animals are being discovered . In both cases, the lipoxygenase pathway plays an important role . In plants, products of this pathway are involved in wound healing, pest resistance, and signaling, or they have antimicrobial and antifungal activity . The first step in the lipoxygenase pathway is the reaction of linoleic or linolenic acids with molecular oxygen, catalyzed by the enzyme lipoxygenase . The hydroperoxy fatty acids thus formed are highly reactive and dangerous for the plant and therefore further metabolized by other enzymes such as allene oxide synthase, hydroperoxide lyase, peroxygenase, or divinyl ether synthase . Recently, these enzymes have been characterized as a special class of cytochrome P450 enzymes . Hydroperoxide lyases cleave the lipoxygenase products, resulting in the formation of omega-oxo acids and volatile C6- and C9-aldehydes and -alcohols . These compounds are major contributors to the characteristic "fresh green" odor of fruit and vegetables . They are widely used as food flavors, for example, to restore the freshness of food after sterilization processes . The low abundance of these compounds in nature and the high demand make it necessary to synthesize them on a large scale . Lipoxygenase and hydroperoxide lyase are suitable biocatalysts for the production of "natural" food flavors . In contrast to lipoxygenase, which has been extensively studied, little is yet known about hydroperoxide lyase . Hydroperoxide lyases from different organisms have been isolated, and a few genes have been published lately . However, the structure and reaction mechanism of this enzyme are still unclear . The identification of this enzyme as a cytochrome P450 sheds new light on its structure and possible reaction mechanism, whereas recombinant expression brings a biocatalytic application into sight.

J Antibiot (Tokyo), 2001 Nov, 54(11), 867 - 73
SW-163A and B, novel immunosuppressants produced by Streptomyces sp; Takahashi K et al.; SW-163A and B, novel immunosuppressants, were isolated from the culture broth of Streptomyces sp . SNA15896 . The molecular formulas of SW-163A and B were determined as C34H42N2O12 and C33H40N2O12 based on the HRFAB-MS analysis, respectively . Both compounds were elucidated to be a large ring ester structure through spectroscopic analyses including various NMR measurements . SW-163A and B showed immunosuppressive and antimicrobial activities in vitro.

Emerg Med Clin North Am, 2002 Feb, 20(1), 69 - 91
Appropriate use of antibiotics for common infections in an era of increasing resistance; Louie JP et al.; In many respects, antibiotics have changed medicine forever . Countless lives have been enhanced and saved with antibiotic use . Unfortunately, the medical community has opened Pandora's box through the casual distribution of outpatient antibiotics . Society will indeed suffer, as well as the medical profession, if antibiotics are not used judiciously . To date, the rate of penicillin resistance has steadily risen in North America and in many other areas of the world . Much of the increase in resistance has been caused by the distribution of antibiotics for viral infections (e.g., bronchitis, colds, or purulent nasal discharge) as well as nonstreptococcal throat infections . Parental pressure for physicians to prescribe antibiotics also has contributed to the rise in antibiotic resistance . The authors have discussed many common pediatric ED infections and have illustrated the key points for making the diagnosis of each . In addition, the authors also recommend the appropriate choice of antibiotics for each disease process, with an emphasis on narrow-spectrum, first-line antimicrobials . Physicians, as the "holders of the prescription pad," should be aware of the problems with increasing bacterial resistance especially ED practitioners who work on the front line . In addition, families and patients should be educated about the harm of inappropriate antibiotic use . The AAP publishes pamphlets for parents that discuss these issues . It is believed, as was seen in Finland and Japan, that judicious use of antibiotics leads to a decrease in resistant bacteria and prolong antibiotic usefulness . This is an issue of great importance to the long-term health of patients . What Benjamin Rush stated in 1789 is true today: "Do not condemn, or oppose, unnecessarily, the simple, prescriptions of your patients . Yield to them in matters of little consequence but maintain an inflexible authority over matters that are essential to life."

Tidsskr Nor Laegeforen, 2001 Nov 20, 121(28), 3300 - 5
{Antibiotic treatment of infectious endocarditis}; Sjursen H; BACKGROUND: Infective endocarditis is a septic condition in which the heart valves and the endocardial surfaces are infected, causing bacteraemia . In Norway, infective endocarditis is the most common infectious disease of the heart and accounts for approximately one case per 1,000 hospital admissions . The mortality rate is 15-40% . MATERIAL AND METHODS: This article presents a review of antimicrobial treatment of infective endocarditis, based on relevant literature and the author's clinical experience . Prophylactic treatment is not described . RESULTS AND INTERPRETATION: Early start of antimicrobial treatment is extremely important in order to avoid destruction of the heart valves and should always be started as soon as endocarditis is suspected and blood cultures have been drawn . The patient must be treated with bactericidal antibiotics in high doses given intravenously for four to eight weeks, depending on the aetiologic agents and the response . Only antibiotics that have been proven effective against endocarditis should be used . The minimal inhibitory concentration (MIC) should be determined for all antibiotics used.

Annu Rev Physiol, 2002, 64, 709 - 48
{beta}-defensins in lung host defense; Schutte BC et al.; Host defenses at the mucosal surface of the airways evolved to present many layers of protection against inhaled microbes . Normally, the intrapulmonary airways are sterile . Airway secretions contain numerous factors with antimicrobial activity that contribute to innate defenses . Many protein and peptide components exert bacteriostatic or bacteriocidal effects against a wide variety of organisms and may act in synergistic or additive combinations . The beta-defensins are a relatively recently described family of peptide antimicrobials that are widely expressed at mucosal surfaces, including airway and submucosal gland epithelia . These small cationic peptides are products of individual genes that exhibit broad-spectrum activity against bacteria, fungi, and some enveloped viruses . Their expression in airway epithelia may be constitutive or inducible by bacterial products or pro-inflammatory cytokines . beta-defensins also act as chemokines for adaptive immune cells, including immature dendritic cells and T cells via the CCR6 receptor, and provide a link between innate and adaptive immunity . Alterations in the function of the beta-defensins may contribute to disease states . Here we review much of the biology of the beta-defensins, including gene discovery, genomic organization, molecular structure, regulation of expression, and function.

J Clin Microbiol, 2002 Feb, 40(2), 607 - 10
Evaluation of automated BACTEC MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to four major antituberculous drugs: comparison with the radiometric BACTEC 460TB method and the agar plate method of proportion; Tortoli E et al.; We evaluated the performance of BACTEC MGIT 960 for automated testing of the susceptibility of 133 strains of Mycobacterium tuberculosis to streptomycin, isoniazid, rifampin, and ethambutol . The BACTEC MGIT 960 results were compared with those obtained with the radiometric BACTEC 460TB system, and when there was disagreement, the method of proportion on agar plates was used as a reference method . Strains resistant to the critical concentration of streptomycin, isoniazid, or ethambutol were also tested with a second, higher concentration . The overall agreement between the two systems was 96.7%, and the 18 discrepancies were resolved in favor of BACTEC 460TB in 11 cases and in favor of BACTEC MGIT 960 in 7, a difference which was not statistically significant . Apart from the assay's low specificity for ethambutol, which was low for the radiometric assay as well, good sensitivity and specificity values characterized BACTEC MGIT 960 . The average time required for completion of the test was 2.5 days shorter with BACTEC 460TB . In conclusion, BACTEC MGIT 960 appears to be a suitable replacement for the radiometric method of antimicrobial susceptibility testing of M . tuberculosis . The problem of frequent contamination of BACTEC MGIT 960 tests needs to be quickly resolved; in fact, 14 strains had to be reprocessed because of contamination.

J Clin Microbiol, 2002 Feb, 40(2), 389 - 94
Characterization of chloramphenicol resistance in beta-hemolytic Escherichia coli associated with diarrhea in neonatal swine; Bischoff KM et al.; Ninety beta-hemolytic Escherichia coli isolates associated with diarrhea in neonatal pigs from multiple farms in Oklahoma were investigated for known associated disease serotypes, virulence factors, ribotypes, and antimicrobial susceptibility phenotypes . Fifteen different serotypes were observed, with 58% of isolates belonging to groups that produce one of three major enterotoxins: O149, O147, and O139 . Thirty percent of the swine E . coli isolates possessed a combination of F4 fimbriae and the heat-labile toxin and heat-stable toxin B enterotoxins . Seventy-three percent of the E . coli isolates were resistant to five or more antibiotics . Interestingly, 53% of swine E . coli isolates exhibited resistance to chloramphenicol (CHL), an antibiotic whose use in food animals has been prohibited in the United States since the mid-1980s . The cmlA gene, which encodes a putative CHL efflux pump, was detected by PCR in 47 of the 48 CHL-resistant isolates, and 4 of these also possessed the cat2 gene, which encodes a chloramphenicol acetyltransferase . The one CHL-resistant isolate that did not contain either cmlA or cat-2 possessed the flo gene, which confers resistance to both florfenicol and CHL . To determine whether CHL-resistant swine E . coli isolates represented dissemination of a clonal strain, all 90 isolates were analyzed by ribotyping . Seventeen distinct E . coli ribogroups were identified, with CHL resistance observed among the isolates in all except one of the major ribogroups . The identification of the cmlA gene among diverse hemolytic enterotoxigenic E . coli strains demonstrates its broad dissemination in the swine production environment and its persistence even in the absence of CHL selection pressure.

Appl Environ Microbiol, 2002 Feb, 68(2), 952 - 6
Rapid two-step procedure for large-scale purification of pediocin-like bacteriocins and other cationic antimicrobial peptides from complex culture medium; Uteng M et al.; A rapid and simple two-step procedure suitable for both small- and large-scale purification of pediocin-like bacteriocins and other cationic peptides has been developed . In the first step, the bacterial culture was applied directly on a cation-exchange column (1-ml cation exchanger per 100-ml cell culture) . Bacteria and anionic compounds passed through the column, and cationic bacteriocins were subsequently eluted with 1 M NaCl . In the second step, the bacteriocin fraction was applied on a low-pressure, reverse-phase column and the bacteriocins were detected as major optical density peaks upon elution with propanol . More than 80% of the activity that was initially in the culture supernatant was recovered in both purification steps, and the final bacteriocin preparation was more than 90% pure as judged by analytical reverse-phase chromatography and capillary electrophoresis.

Appl Environ Microbiol, 2002 Feb, 68(2), 576 - 81
Antimicrobial resistance of Escherichia coli O157 isolated from humans, cattle, swine, and food; Schroeder CM et al.; A total of 361 Escherichia coli O157 isolates, recovered from humans, cattle, swine, and food during the years 1985 to 2000, were examined to better understand the prevalence of antimicrobial resistance among these organisms . Based on broth microdilution results, 220 (61%) of the isolates were susceptible to all 13 antimicrobials tested . Ninety-nine (27%) of the isolates, however, were resistant to tetracycline, 93 (26%) were resistant to sulfamethoxazole, 61 (17%) were resistant to cephalothin, and 48 (13%) were resistant to ampicillin . Highest frequencies of resistance occurred among swine isolates (n = 70), where 52 (74%) were resistant to sulfamethoxazole, 50 (71%) were resistant to tetracycline, 38 (54%) were resistant to cephalothin, and 17 (24%) were resistant to ampicillin . Based on the presence of Shiga toxin genes as determined by PCR, 210 (58%) of the isolates were identified as Shiga toxin-producing E . coli (STEC) . Among these, resistance was generally low, yet 21 (10%) were resistant to sulfamethoxazole and 19 (9%) were resistant to tetracycline . Based on latex agglutination, 189 (52%) of the isolates were identified as E . coli O157:H7, among which 19 (10%) were resistant to sulfamethoxazole and 16 (8%) were resistant to tetracycline . The data suggest that selection pressure imposed by the use of tetracycline derivatives, sulfa drugs, cephalosporins, and penicillins, whether therapeutically in human and veterinary medicine or as prophylaxis in the animal production environment, is a key driving force in the selection of antimicrobial resistance in STEC and non-STEC O157.

Microb Drug Resist, 2001 Winter, 7(4), 335 - 42
Antibiotic persistence: the role of spontaneous DNA repair response; Debbia EA et al.; Persisters are a small proportion of a bacterial population that exists in a physiological state permitting survival despite the lethal activity of antibiotics . To explain this phenomenon, it has been suggested that persisters are bacteria repairing spontaneous errors of DNA synthesis . To verify this assumption, Escherichia coli AB1157 and its lexA3 derivative were exposed to a dose 6x MIC of various antibiotics representative of different molecular mechanisms of action (ampicillin, ceftriaxone, meropenem, amikacin, ciprofloxacin) . Bacterial cell counts, after 24 hr of exposure to the antimicrobials, revealed a reduction of about 90% of viable organisms in the lexA3 strains in comparison to the lexA+ . In several cases, the number of colony-forming units decreased below the limit of assay . This behavior was noted with all antibiotics used, alone or in combination (amikacin plus ceftriaxone and amikacin plus ciprofloxacin) . The same experiments were repeated using E . coli AB1157 cultured in the presence of mitomycin C (0.25x MIC), and the number of survivors exceeded by about 90% the values found in the nonexposed control . In contrast, in the sulA background, mitomycin C reacted synergically with all the antibiotics tested causing a strong reduction of the survivors in comparison with the control . The addition of chloramphenicol (0.125x MIC), on the contrary, caused a reduction of the number of survivors of about 90% . These findings indicate that, when DNA repair is active (a mechanism known to block cell division), the number of survivors is greater than that observed with lexA3 . Thus, in addition to other possible explanations, persisters might be a fraction of bacteria that during antibiotic treatment are not growing because they are repairing spontaneous errors of DNA synthesis.

Boll Chim Farm, 2001 Nov-Dec, 140(6), 397 - 400
Synthesis and antimicrobial activity of some imidazo-{1,2-a}pyridine-2- carboxylic acid arylidenehydrazide derivatives; Turan-Zitouni G et al.; Imidazo{1,2-a}pyridine-2-carboxylic acid, ethyl esters were reacted with hydrazine hydrate to furnish imidazo{1,2-a}pyridine-2-carboxylic acid hydrazide . The hydrazides formed were treated with various aldehydes to obtain 28 imidazo{1,2-a}pyridine-2-carboxylic acid arylidenehydrazides . Antimicrobial activity of the compounds were examined.

FASEB J, 2002 Mar, 16(3), 429 - 31 Epub 2002 Jan 30.
Cathepsin D produces antimicrobial peptide parasin I from histone H2A in the skin mucosa of fish; Cho JH et al.; Parasin I is a potent 19-residue antimicrobial peptide isolated from the skin mucus of wounded catfish (Parasilurus asotus) . Here we describe the mechanism of parasin I production from histone H2A in catfish skin mucosa on epidermal injury . Cathepsin D is found to exist in the mucus as an inactive proenzyme (procathepsin D), and a metalloprotease, induced on injury, cleaves procathepsin D to generate active cathepsin D . This activated form of cathepsin D then cleaves the Ser19-Arg20 bond of histone H2A to produce parasin I . Immunohistochemical analysis reveals that unacetylated histone H2A, a precursor of parasin I, and procathepsin D are present in the cytoplasm of epithelial mucous cells and that parasin I is produced on the mucosal surface on epidermal injury . Western blot analysis shows that parasin I is also present in the skin mucus of other fish species . Furthermore, parasin I shows good antimicrobial activity against fish-specific bacterial pathogens . Taken together, these results indicate that cathepsin D and a metalloprotease participate in the production of parasin I from histone H2A and that parasin I contributes to the innate host defense of the fish against invading microorganisms.

Biochem Biophys Res Commun, 2002 Feb 8, 290(5), 1602 - 8
Structural investigation of the hedamycin:d(ACCGGT)2 complex by NMR and restrained molecular dynamics; Owen EA et al.; Hedamycin, a member of the pluramycin family of drugs, displays a range of biological responses including antitumor and antimicrobial activity . The mechanism of action is via direct interaction with DNA through intercalation between the bases of the oligonucleotide and alkylation of a guanine residue at 5'-PyG-3' sites . There appears to be some minor structural differences between two earlier studies on the interaction of hedamycin with 5'-PyG-3' sites . In this study, a high-resolution NMR analysis of the hedamycin:d(ACCGGT)2 complex was undertaken in order to investigate the effect of replacing the thymine with a guanine at the preferred 5'-CGT-3' site . The resultant structure was compared with earlier work, with particular emphasis placed on the drug conformation . The structure of the hedamycin:d(ACCGGT)2 complex has many features in common with the two previous NMR structures of hedamycin:DNA complexes but differed in the conformation and orientation of the N,N-dimethylvancosamine saccharide of hedamycin in one of these structures . The preferential binding of hedamycin to 5'-CG-3' over 5'-TG-3' binding sites is explained in terms of the orientation and location of the N,N-dimethylvancosamine saccharide in the minor groove . (c)2002 Elsevier Science (USA).

J Leukoc Biol, 2002 Feb, 71(2), 238 - 46
Bacterial metabolite interference with maturation of human monocyte-derived dendritic cells; Saemann MD et al.; Dendritic cells (DC), the most potent APC, are central to antimicrobial immunity . Because of evolutionary pressure, it is reasonable that pathogens have evolved strategies to also subvert this host-defense mechanism . In the present study, we describe a novel way of bacterial interference with DC maturation . The bacterial metabolite n-butyrate, which occurs physiologically in high concentrations in the gastrointestinal tract and has well-known anti-inflammatory effects, is able to prevent LPS-induced maturation of DC resulting in a reduced capability to stimulate T cells . In particular, n-butyrate prevents homotypic DC clustering, inhibits IL-12 while sparing IL-10 production, and at the molecular level, blocks NF-kappa B translocation . These results demonstrate efficient targeting of DC function by a bacterial metabolite, which might explain the particular type of immune responsiveness in the presence of this bacterial agent as exemplified in the gastrointestinal tract.

Am J Clin Dermatol, 2002, 3(1), 1 - 7
Impact of increasing antimicrobial resistance on wound management; Filius PM et al.; Wound infection with antimicrobial-resistant bacteria may result in prolonged debility of the patient and increased healthcare costs . Avoidance of the development of resistance therefore needs increasing attention in the management of patients with wound infections . Antimicrobial use is the major determinant in the development of resistance . Knowledge of the criteria for wound infections, the causative pathogens, and their prevailing susceptibility patterns is a prerequisite for the rational prescribing of antimicrobials . Since the benefits of wound debridement and wound irrigation have been proven, prescribing antibacterials should not usually be the initial treatment strategy in the management of infected wounds . The use of systemic antibacterials is only indicated when infection appears to be spreading through the subcutaneous soft tissues and in cases of ascending limb infection or severe sepsis . To minimize the selection pressure of individual antibacterials on the normal flora of the skin and gut, narrow-spectrum agents are to be preferred . Empirical treatment with systemic antibacterials should be adapted, based on the results of wound cultures . Topical antibacterials have also been successfully used in the management of patients with infected wounds . Defining guidelines for the rational use of systemic and topical antimicrobials is an important tool to limit and control the development of resistance . Because of geographical differences in resistance rates and methodological differences in published reports, local surveillance data should be available to assist clinicians in the development of these guidelines . New systemic and topical agents should be assessed at an early stage of development for their potential for selection of resistance . Research is needed on the applicability of alternatives to antimicrobials in the management of patients with wound infections in order to reduce the future risk of antimicrobial resistance.

Transgenic Res, 2001 Dec, 10(6), 555 - 69
Transgenic tobacco plants expressing the maize Cat2 gene have altered catalase levels that affect plant-pathogen interactions and resistance to oxidative stress; Polidoros AN et al.; Transgenic tobacco genotypes expressing the maize Cat2 gene were developed with altered catalase (CAT) levels that resulted in a moderate increase of CAT activity in two transgenic lines . Bacterial infection, with a pathogen that does not share homology with the transgene, caused local and systemic down-regulation of the steady state mRNA levels of the 35S-driven transgene in a manner resembling post-transcriptional gene silencing (PTGS) . Phenotypic symptoms of hypersensitive response (HR) and systemic acquired resistance (SAR) were similar in control SR1 and the transgenic genotypes . Induction of hin1, used as a molecular marker of plant responses to invading bacteria, displayed a similar pattern between control and transgenic lines, but some variation in the levels of expression was observed . The major difference was recorded in the ability of the plants to restrict bacterial growth during HR . All transgenic lines were more sensitive than control SR1, with two lines exhibiting a significantly reduced capacity to inhibit bacterial growth . This is consistent with the putative enhanced capacity of transgenic lines containing the maize Cat2 gene to more effectively remove H2O2, which may act as a direct antimicrobial agent . Steady state mRNA levels of PR-1 and PR-5 varied among the genotypes, possibly indicating differences in strength of the SAR signal . Transgenic line 2, which was the most sensitive during HR, was most effective in restricting bacterial growth during SAR . This indicates that a reverse correlation might exist between the severity of infection during HR and the ability to inhibit bacterial growth during SAR . Growth under high light conditions affected plant-pathogen interactions in control SR1, as well as in transgenic line 8 . Early induction and higher expression of PR-1 and PR-5 was detected in both SR1 and line 8 in high light-grown plants as compared with their low light-grown counterparts . Our data indicate that growth under high light conditions can predispose plants to better resist pathogen attack, and may amplify local and systemic defense signals . Finally, one transgenic line, which exhibited 1.3-fold higher average CAT activity in comparison with the untransformed SR1 control, suffered significantly less methyl viologen (MV) damage than untransformed control plants at moderate and high MV concentrations.

Immunol Res, 2001, 24(3), 273 - 87
Sepsis-induced immunosuppression: from bad to worse; Reddy RC et al.; The sepsis syndrome is characterized by the acute release of a variety of inflammatory mediators, which often result in detrimental effects to the host . The release of these mediators is regulated and counterbalanced by the coordinated expression of antiinflammatory molecules . It is the balance between the expression of pro- and antiinflammatory mediators that often determines the magnitude of early tissue injury and subsequent risk of infectious complications . As our understanding of the pathophysiology of sepsis continues to evolve, we have gained a greater appreciation for the effects that sepsis and similar states of overwhelming stress have on host antimicrobial immunity . A number of functional defects in leukocytes isolated from sepsis patients have been characterized . These defects include diminished expression of important cell surface antigens, dysregulated cytokine production, alterations in antigen-presenting ability, and accelerated apoptosis . Impaired leukocyte function has important clinical ramifications, as high mortality rates have been observed in patients displaying evidence of sepsis-induced immune deactivation . In this article, we review the current literature supporting evidence of dysregulation of host immunity occurring during sepsis syndrome, characterize the underlying pathophysiology, and describe novel therapeutic interventions directed at augmenting host immunity during sepsis.

J Chromatogr B Biomed Sci Appl, 2001 Dec 5, 765(1), 37 - 43
Determination of BMS-284756, a new quinolone, in mouse serum by high-performance liquid chromatography with fluorescence detection; Xuan D et al.; A sensitive, simple, and accurate method for determination of BMS-284756, a novel des-F(6)-quinolone antimicrobial agent in mouse serum was developed by HPLC with fluorescence detection . Sample preparations were carried out by protein precipitation with the addition of acetonitrile, followed by evaporation of the acetonitrile to dryness . The resultant residual was then reconstituted in 0.01 M HCl and injected onto a Nucleosil 100 10 microm, C18 25 cm x 4.6 mm analytical column . The mobile phase consisted of acetonitrile-0.01 M NaH2PO4 (20:80, v/v) with 0.01 M tetrabutylammonium hydrogen sulfate . The fluorescence of the column effluent was monitored at an excitation wavelength of 290 nm and an emission wavelength of 418 nm . The assay was shown to be linear from 0.2 to 10.0 microg/ml (R2=0.998) . Mean recovery was determined as 95.1% . Inter- and intra-assay precisions were <6% RSD . The HPLC method developed has been applied to determine the pharmacokinetics of BMS-284756 in a murine bacterial infection model.

Ann Pharmacother, 2002 Jan, 36(1), 167 - 9
Amphotericin B in lung transplant recipients; Klepser ME; Although the verdict may still be out on the clinical utility of prophylactic administration of amphotericin B, the findings presented by Marra et al . strengthen the argument for its theoretical use by demonstrating that a relatively reproducible range of concentrations can be achieved in the target patient group . Additionally, it was demonstrated that at an inhaled dose of 30 mg, amphotericin B concentrations at the interface of epithelial lining fluid and the lung tissue, the battleground for host invasion, approach therapeutically relevant concentrations . Even though the debate over the utility of aerosolized administration of antimicrobials is far from over, data continue to accumulate that demonstrate the tolerability and describe the characteristics of drug distribution of nebulized amphotericin B . Even with the absence of definitive clinical data, aerosolized administration of amphotericin B may become a viable option for prophylaxis against serious pulmonary fungal infections owing to the severity of disease, lack of serious toxicities associated with this route of administration, and pharmacokinetic and susceptibility data, suggesting a theoretical basis for activity.

Int J Antimicrob Agents, 2002 Jan, 19(1), 71 - 4
In vivo activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with dapsone, against Mycobacterium leprae; Dhople AM; The antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, either singly or in combination with dapsone against Mycobacterium leprae, were evaluated in vivo using a mouse footpad model . When fed to mice at concentration of 0.05% in diet, epiroprim completely inhibited the growth of both dapsone-sensitive and dapsone-resistant strains of M . leprae in the footpads of mice and the effects were bactericidal . To achieve similar effects, the concentration of dapsone in the diet had to be 0.0005 and 0.01%, respectively . When used in combination, the concentrations of the drugs in the diet could be lowered by 50-80% and still achieve bactericidal effects . The data support the earlier results on in vitro studies and suggest the use of epiroprim in the multidrug regimen in the treatment of leprosy.

Int J Antimicrob Agents, 2002 Jan, 19(1), 61 - 6
Association between initial empirical therapy and decreased length of stay among veteran patients hospitalized with community acquired pneumonia; Lentino JR et al.; This investigation assessed the impact of initial empirical antimicrobial therapy on the outcome of therapy for community acquired pneumonia (CAP) patients and on patients' length of stay (LOS) in the hospital . Hospital records for 165 patients with pneumonia admitted to the Edward Hines, Jr . VA Hospital between 1 October 1997, and 31 March 2000, were reviewed . Criteria for CAP were met for 92 of 165 patients . Comparisons were made between patients treated with azithromycin and with other parenteral antibiotics (the reference group) . No statistical differences were observed between the treatment groups for the risk factors . The azithromycin group patients were slightly older with a mean age of 69 years versus 66 years (P=0.23) . Patients treated with parenteral azithromycin had on average, a shorter length of hospitalization namely 4.6 days compared with 9.7 days for patients treated with the other antibiotics (log-rank test, P=0.0001) . In order to make the two groups of patients more alike we considered patients' data set without intensive care unit (ICU) admissions . The conclusion was the same namely azithromycin monotherapy was associated with a decreased duration of hospital stay.

Int J Antimicrob Agents, 2002 Jan, 19(1), 9 - 20
Antimicrobial susceptibility test: from bacterial population analysis to therapy; Scavizzi MR et al.; The statistical methods and parameters commonly used to define bacterial susceptibility to antibiotics in vitro such as MIC(50), linear regression or others, usually lead to a considerable loss of information: they do not take into account the heterogeneity of the bacterial population . In contrast, multivariate data analyses are more adapted to the description of biological systems . In this way, a population of a given bacterial species can be separated into homogenous classes corresponding to the different sensitivity and resistance phenotypes . The applications of this mathematical approach include: (i) a new model for more relevant interpretation of antimicrobial susceptibility test results; (ii) numerical estimation of breakpoints having a known risk; (iii) calibration of a technique relative to a reference technique; (iv) detection of strains with new phenotypes; (v) in vitro evaluation of the activity of new compounds.

FEMS Microbiol Lett, 2002 Jan 10, 206(2), 143 - 9
Role of membranes in the activities of antimicrobial cationic peptides; Hancock RE et al.; Cationic amphiphilic peptides that are found throughout nature have very broad-spectrum activities against microbes . The initial sites of interaction are with microbial membranes . Although dogma suggests that their lethal action involves disruption of the cytoplasmic membranes, a number of cationic peptides can traverse intact membranes to interact with internal targets.

Peptides, 2002 Jan, 23(1), 1 - 6
A tridecapeptide possesses both antimicrobial and protease-inhibitory activities; Li Q et al.; A 13-residue synthetic peptide (Rev4) was designed based on indolicidin, an antimicrobial peptide from bovine neutrophils . The synthetic peptide retains high antimicrobial activity . When tested for its stability in tobacco leaf extracts, Rev4 was highly stable compared to another antimicrobial peptide, magainin . When mixed with Rev4, magainin was protected from degradation by the leaf extract . Our results show that Rev4 is a potent protease inhibitor which selectively inhibits three out of four different types of proteases . Four other synthetic peptides were tested and the results were suggestive of no correlation between their antimicrobial and protease inhibitory activities.

Am J Health Syst Pharm, 2002 Jan 1, 59(1), 33 - 41
Management of systemic candidal infections in the intensive care unit; Kam LW et al.; Risk factors and treatment strategies for systemic candidal infections in the intensive care unit (ICU) are discussed . The past two decades have seen a dramatic increase in the frequency of infections caused by Candida species . Risk factors associated with candidemia include treatment with multiple antimicrobials for extended periods, presence of central venous catheters, total parenteral nutrition, colonization by Candida species, abdominal surgery, prolonged stay in the ICU, and compromised immune status . Since the 1960s, conventional amphotericin B has been the primary treatment option for fungal infections . Although effective, amphotericin B has extensive toxicity . Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease nephrotoxicity and improve drug delivery . Practitioners have also been offered alternatives by the introduction of less toxic azole antifungals, such as ketoconazole, fluconazole, and itraconazole; however, their widespread use has resulted in other problems, such as the selection of resistant isolates . There is controversy concerning fluconazole's effectiveness . In the treatment of systemic candidal infections, especially in critically ill patients . Clinical trials do not support the prophylactic or empirical use of fluconazole in the ICU . Treating patients who have no microbiological evidence of infection provides no therapeutic benefit and shifts the fungal flora to noncandidal strains that are more resistant to fluconazole . Patients in ICUs are often susceptible to systemic candidal infection . Preemptive therapy with fluconazole may reduce mortality in high-risk patients . Fluconazole and amphotericin B appear equally effective in treating established systemic candidal infections.

J Calif Dent Assoc, 2001 Dec, 29(12), 825 - 37
Strategies to treat infected root canals; Siqueira Junior JF; Periradicular lesions are diseases either primarily or secondarily caused by microorganisms and therefore they must be prevented or treated accordingly . If the professional is well-versed in both preventing and eliminating the root canal infection, the success rate of endodontic therapy may exceed 90 percent . The present paper discusses theoretical and practical aspects of effective antimicrobial endodontic therapy and delineates strategies to effectively control root canal infections.

Nat Immunol, 2002 Feb, 3(2), 121 - 6
Drosophila innate immunity: an evolutionary perspective; Hoffmann JA et al.; In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides . These defense mechanisms are activated via two distinct signaling pathways . One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections . Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins . We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila.

J Infect Chemother, 2000 Dec, 6(4), 211 - 5
Detection of antimicrobial-treated Chlamydia trachomatis with Amplicor PCR test kit; Takahashi S et al.; A polymerase chain reaction (PCR) method for the detection of Chlamydia trachomatis has been developed and is now available in the clinical setting . However, one of the major problems with this method is possible false-positive detection posttreatment . Nonviable C . trachomatis was established by in-vitro exposure to an antimicrobial agent, and we tried to detect the nonviable cells (NVCs) of C . trachomatis by PCR with variant primer sets . C . trachomatis strains (D/UW-3/Cx) were cultured in a medium containing the antimicrobial agent, at 8 x MIC (minimal inhibitory concentration) 15 to 20 h postinfection . Amplicor and two sets of PCR primers were used to detect the DNA of NVCs . Serial passages of NVCs were done five times . All samples were positive on Amplicor, and all except the fourth passage were positive for the two sets of primers . Although the PCR test appears to be valuable, NVCs may possibly be detected by this method, and this may be clinically responsible for the false detection of C . trachomatis after appropriate antimicrobial chemotherapy.

J Infect Chemother, 2000 Dec, 6(4), 206 - 10
Evaluation of the activity of antimicrobial agents against Legionella pneumophila multiplying in a human monocytic cell line, THP-1, and an alveolar epithelial cell line, A549; Kunishima H et al.; The intracellular activity of three antimicrobial agents, erythromycin, clarithromycin, and ciprofloxacin, against Legionella pneumophila was examined in the human monocyte-derived cell line, THP-1, and the human alveolar epithelial cell line, A549 . L . pneumophila multiplied by three- to four-log in THP-1 and by two- to three-log in A549 after 48-h incubation . The activity of the two macrolides was markedly greater in A549 than in THP-1, while ciprofloxacin exhibited similar activity in both cell lines . The intracellular concentrations of the two macrolides were markedly higher in A549 than in THP-1, while those of ciprofloxacin were almost equal in both types of cell lines . The intracellular activity of antimicrobial agents and the intracellular growth of L . pneumophila vary with different types of host cells.

J Infect Chemother, 2000 Sep, 6(3), 148 - 50
Evaluation of in-vitro activity of new quinolones, macrolides, and minocycline against Mycoplasma pneumoniae; Ikejima H et al.; We made a comparative study of the in-vitro activities of grepafloxacin (GPFX), ofloxacin (OFLX), erythromycin (EM), clarithromycin (CAM), roxithro-mycin (RXM), and minocycline (MINO) against 20 strains of Mycoplasma pneumoniae (17 clinical isolates and 3 standard strains) . The minimum inhibitory concentration (MIC)90-to-minimum bactericidal concentration (MBC)90 ratio showed that the new quinolones have bactericidal effects on M . pneumoniae . Thus, it is expected that the new quinolones, especially grepafloxacin, will be clinically useful antimicrobial agents for the treatment of M . pneumoniae infection because of their good pharmacokinetic properties and bactericidal action.

J Infect Chemother, 2000 Mar, 6(1), 65 - 7
In-vitro and in-vivo antibiotic susceptibilities of Lyme disease Borrelia isolated in China; Li M et al.; The antibiotic susceptibilities of seven Borrelia burgdorferi sensu lato isolates from Ixodes persulcatus in China were examined by in-vitro microdilution minimum inhibition concentration (MIC) and macrodilution minimum bactericidal concentration (MBC) methods . All isolates tested were susceptible to amoxicillin, erythromycin, and minocycline . The MICs of these drugs for the Chinese isolates were 0.025-0.1 microg/ml, <0.012-0.05 microg/ml, and <0.012-0.05 microg/ml, respectively . The MBCs were 0.1-0.39 microg/ml, <0.012-0.2 microg/ml, and 0.025-0.39 microg/ml, respectively . The in-vivo antimicrobial susceptibilities of the Chinese Borrelia isolates to two test drugs, amoxicillin and minocycline, were evaluated using ddY mice . Mice were infected by subcutaneous inoculation into the right hind footpad . When infection was confirmed, the mice were treated by subcutaneous injection of the test drugs into the back . Amoxicillin and minocycline, which possessed high in-vitro activities against Lyme disease Borrelia, provided good protection against borreliosis in this animal model . Higher doses of these drugs resulted in elimination of the Lyme disease spirochete from all animals receiving this course of treatment . The 50% curative doses (CD50) of amoxicillin and minocycline were 8.7 mg/kg and 3.1 mg/kg, respectively . This suggested that amoxicillin and minocycline could be useful for the treatment of Chinese Borrelia infection.

What Is Protein?, What Is Nitrification?, What Is Bioassay?, What Is Bioengineering?, What Is Dna?, o, Microbiology, a, Microbe, i, Microorganisms, n, Bacteria, n, Microbes, n, Sepsis, e, Escherichia coli, i, Micrococci, i, Wastewater, o, Antibiotics, s, Staphylococcus aureus, n, Bacteroides, n, Antimicrobial, n, Escherichia coli, s, Sepsis, o, Clostridia, n, Staphylococcus, s, Bacteroides, n, Clostridia, e, Streptococci, a, Bacillus subtilis, s, Yeasts, o, Cryptococci, r, Antibiotics, o, Staphylococcus aureus, n, Escherichia coli

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005