Nippon Rinsho, 2001 Apr, 59(4), 750 - 5 {Clinical characteristics of emerging multiple-drug-resistant gram-negative rods producing extended-spectrum beta-lactamases (ESBLs)}; Yamaguchi T et al.; The prevalence of organisms producing extended-spectrum beta-lactamases(ESBLs) has been increasing all over the world . ESBLs confer resistance to cefotaxime, ceftazidime, aztreonam, extended-spectrum penicillins, and structurally related beta-lactams in clinical isolates of K . pneumoniae and E . coli . Under the influence of antimicrobial agents, bacteria that primarily produce TEM-type or SHV-type beta-lactamases developed point mutations in structural genes which served to extend the substrate specificity of the enzymes . Infections caused by ESBLs producing isolates are difficult to detect with current susceptibility tests, and are difficult to treat . This article provides an historical overview of the emergence of ESBLs carrying gram-negative rods and consider how to treat their infections. Nippon Rinsho, 2001 Apr, 59(4), 660 - 5 {Molecular biology of the mechanism of acquisition of antimicrobial-resistance}; Hashimoto H; There are two ways for a bacterium to acquire antimicrobial-resistance: 1) Horizontal transfer of resistance gene(s) from outside, 2) Mutation of its own chromosome . The former case includes conjugation, transduction and transformation . Resistance genes usually locate on transposon or integron and have inverted or direct repeats on both sides, or link to a special sequence at one side . A target of an antibiotic is an essential enzyme for the bacterium to survive, and the corresponding gene is located on the chromosome . The mutation of the essential gene may cause resistance to antimicrobials by decreasing the affinity of enzyme to the drug . The mutation of genes for drug influx or efflux also causes antimicrobial resistance. Nippon Rinsho, 2001 Apr, 59(4), 645 - 51 {Present situation of drug resistance and future prospects}; Inoue M et al.; Antibiotic resistance has evolved over 60 years from a merely microbiological curiosity to a serious medical problem in hospitals . Resistance has been reported in almost all species of bacteria to various classes of antimicrobial agents including recently evaluated ones . Bacteria regulated resistance by different mechanisms . Inappropriate use of an antimicrobial agent selects resistant strains much more frequently . Since it is not expected that some epoch-making new antimicrobial agents will be developed in the near future, proper use of existing antimicrobial agents which is based on the mechanisms of action of antimicrobial agents and of resistance of bacteria, and of control of nosocomial infection are very important to reduce the further spread of resistant bacteria . With the search for natural sources of new antimicrobial substances now appearing frustrated, the genomic approach in the 21st century may be the only fruitful way to develop truly novel chemotherapeutic agents against bacterial diseases. Arzneimittelforschung, 2001, 51(3), 264 - 7 Antimicrobial activity of thiamphenicol-glycinate-acetylcysteinate and other drugs against Chlamydia pneumoniae; Lombardi A et al.; Chlamydia pneumoniae is responsible for respiratory tract infections of both upper and lower respiratory tract . Although this bacterium is one of the most wide-spread pathogens of man, there are limited data on the antibiotic treatment of C . pneumoniae infections . The aim of this study has been to evaluate the in vitro activity of thiamphenicol glycinate acetylcysteinate (TGA, CAS 20192-91-0) in comparison with molecules with established activity against C . pneumoniae, as well as macrolides and quinolones . The results have shown that TGA and clarithromycin (CAS 81103-11-9) are the most active drugs tested, but it is important to underline that the minimal inhibitory concentration (MIC) ranges of TGA are very much lower than the breakpoint of thlamphenicol for the respiratory pathogens . In conclusion, the good antimicrobial in vitro activity of TGA against C . pneumoniae together with its in vivo characteristics, in particular the high concentration reached in lung and the combination with the mucolytic agent N-acetylcysteine (NAC, CAS 616-91-1), can make a valid choice in the treatment of respiratory tract infections caused by C . pneumoniae . These findings need further evaluation by clinical studies. Am J Ther, 2000 Nov, 7(6), 393 - 8 Osteoarticular tuberculosis: current diagnosis and treatment; Sequeira W et al.; Tuberculous synovitis frequently presents as a monoarthritis of weight-bearing joints such as the hip, knee, or ankle . Owing to its low incidence in developed countries, the diagnosis is often delayed for months to years . Early diagnosis with a synovial biopsy permits prompt antituberculous therapy and substantially improves the prospect of preservation of joint structure and function . Initial treatment typically includes combination therapy with four drugs (isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol) because of the frequency of isoniazid resistance . Antimicrobial therapy should be of at least 9 months' duration, longer in immunocompromised hosts . Partial synovectomy and other surgical procedures should be restricted to joints with severe cartilage destruction, large abscesses, joint deformity, multiple drug resistance, or atypical mycobacteria. Pediatr Infect Dis J, 2001 Mar, 20(3), 362 - 9 Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia; Mustafa MM et al.; BACKGROUND: In view of the recent trend toward monotherapy in the treatment of bacterial infection, we evaluate the clinical efficacy and safety of cefepime vs . ceftazidime for the empiric treatment of febrile episodes in neutropenic pediatric cancer patients . METHODS: In a single site, open label study, 104 neutropenic pediatric cancer patients {96% with absolute neutrophil count (ANC) of <500 neutrophils/mm3} with a median age of 6 years were randomized (1:1) to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose every 8 h; < or = 6 g/day) for empiric treatment of fever (temperature >38.0 degrees C occurring at least twice in 24 h, or single >38.5 degrees C) . Febrile episodes were classified as either microbiologically or clinically documented infection or fever of unknown origin . Therapy continued until the ANC was > or = 1,000 neutrophils/mm3 or there was an increasing ANC in low risk patients (maximum duration of treatment, 8 weeks) . The primary efficacy endpoints assessed were clinical and microbiologic response to assigned drug therapy . Secondary outcome measures were rate of early discontinuation of study drug and use of concomitant antibiotic therapy to modify initial study drug regimen . RESULTS: Of 68 patients who could be evaluated for efficacy, 74% (26 of 35) of cefepime-treated patients and 70% (23 of 33) of ceftazidime-treated patients responded to treatment . The small number of study patients precluded statistical analysis of results . In a modified intent-to-treat analysis, 59% of the patients treated with cefepime and 47% of ceftazidime-treated patients responded to therapy . Cefepime patients developed fewer new infections than ceftazidime patients (9% vs . 21%, respectively) and early discontinuation of study drug therapy occurred slightly more often in the ceftazidime group . Further, the use of concomitant systemic antimicrobial therapy (mostly vancomycin) occurred less often in the cefepime-treated patients, as compared with the ceftazidime group {35% {17 of 49} vs . 44% (24 of 55), respectively} . No deaths or serious adverse events were considered to be related to study therapy . The most frequent adverse event was rash that was moderate in severity, and it occurred equally in both groups . CONCLUSION: Cefepime appears to be safe and effective compared with ceftazidime for initial empiric therapy of febrile episodes in neutropenic pediatric cancer patients. Scand J Infect Dis, 2001, 33(3), 219 - 21 Influence of an infectious disease consulting service on quality and costs of antibiotic prescriptions in a university hospital; Lemmen SW et al.; An infectious disease consulting service was set up at a large tertiary university hospital in 1996 to evaluate and to improve antibiotic prescription patterns . Treatment guidelines for the most common bacterial infections were implemented . On daily ward rounds antibiotic therapies without evidence of an infectious disease were stopped and inappropriate regimens were changed by an infectious disease specialist . During a 6-month prospective intervention period, 3,528 patients were studied on 13 wards of the department of internal medicine; 513 of these patients (14.5%) received antibiotic therapy . These treatment courses were evaluated as adequate in 394 cases (76.8%) and incorrect in 119 cases (23.2%) . Inadequate antibiotic substances were chosen in 72 out of 119 cases (60.5%) and there was no indication for treatment in 38 out of 119 cases (32%) . Pathogen-specific therapies were inadequate significantly more often than empirical antimicrobial therapies (p < 0.001) . In addition, the duration of the perioperative prophylaxis could be limited to 1 d . Comparing the intervention period with a 3-month control interval without an infectious disease consulting service, a total of 31,510 Euro (including the costs for the infectious disease specialist) could be saved . No increase in infection-related mortality or length of stay was observed . These data show that an infectious disease consulting service optimizes antibiotic usage, and is cost-effective as a result of a significant cost reduction in hospitals, while not interfering with the quality of medical care. Scand J Infect Dis, 2001, 33(3), 211 - 4 Pulmonary imaging and function in the common cold; Puhakka T et al.; The common cold is generally considered to be an upper respiratory tract infection . We studied the lower respiratory tract in 76 otherwise healthy young adults with the common cold . Viral infection was diagnosed in 56 (74%) of the 76 subjects . Rhinovirus was detected in 42 (55%) subjects . Chest radiography (CR) and high-resolution computerized tomography (HRCT) were carried out in 40 subjects on day 7, and pulmonary function testing with bronchodilator challenge was carried out in 36 patients on days 7 and 21 of the study . Clinical examinations were carried out on days 1, 7 and 21 . The subjects recorded their symptoms on a diary card for 20 d . The mean duration of cough was 8.4 (SD 6.5) d and that of sputum production 5.9 (SD 6.4) d . No abnormal findings were detected in the lungs on auscultation . CR and HRCT showed no pulmonary changes associated with the common cold . No clinically remarkable increases were seen in peak expiratory flow, forced expiration volume in 1 s or forced vital capacity after bronchodilator challenge on either days 7 or 21 . All patients made a clinical recovery without antimicrobial therapy within 21 d . We conclude that the common cold in young otherwise healthy adults is an upper respiratory tract infection and that clinically important abnormalities in the lower respiratory tract are rare. Scand J Infect Dis, 2001, 33(3), 200 - 5 Limited diagnostic usefulness of antibodies to cytoplasmic proteins of Brucella in early-treated human brucellosis; Baldi PC et al.; Antibodies to cytoplasmic proteins (CP) of Brucella have been shown to be useful for the diagnosis of human brucellosis; however, some early-diagnosed patients lack such an antibody response while having high titers of antibodies to lipopolysaccharide (LPS) . To address which factors determine this serological discrepancy in the early stages of brucellosis we examined the antibody response to CP and LPS of 21 patients involved in an outbreak of B . melitensis infection who had a short duration of clinical illness at diagnosis (3-40 d) . At diagnosis, antibodies to LPS (IgM and/or IgG) were found in all patients, while anti-CP antibodies were detected in 16 subjects (76%) . At 6 weeks post-diagnosis IgG to CP (with or without IgM) had been detected in 13 patients and IgM alone had been found in 4; however, 4 other patients (19%) had no response to CP . No significant differences were found between these 3 groups in terms of age, gender, antimicrobial agents or factors that could hamper the immune response . Notably, however, the 4 non-responders and 3 of the 4 patients having only IgM to CP had started antibiotic therapy within 14 d post-symptoms, while treatment was started later in 9 of 13 patients who developed anti-CP IgG . In addition, maximum titers of IgG to CP tended to be lower in early-treated patients . These results suggest that very early antibiotic therapy hampers the antibody response to Brucella CP but has little impact on the anti-LPS response . Given the higher specificity of the former and the higher sensitivity of the latter, both reactivities should be measured in order to diagnose human brucellosis. Clin Infect Dis, 2001 May 1, 32(9), 1281 - 9 Epub 2001 Apr 10. Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections; Principi N et al.; In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs) . The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999 . Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M . pneumoniae and C . pneumoniae antibodies . Nasopharyngeal aspirates for the detection of M . pneumoniae and C . pneumoniae were obtained on admission . Acute M . pneumoniae infections in 210 patients (34.3%) and acute C . pneumoniae infections in 87 (14.1%) were diagnosed . Fifteen of the 18 children with M . pneumoniae and/or C . pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides . Our study confirms that M . pneumoniae and/or C . pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents. Antimicrob Agents Chemother, 2001 May, 45(5), 1581 - 4 Antimicrobial susceptibilities of unique Stenotrophomonas maltophilia clinical strains; Valdezate S et al.; Susceptibility to 41 antimicrobials was studied with 99 Stenotrophomonas maltophilia strains, and different pulsed-field gel electrophoresis profiles were identified among 130 prospectively collected isolates . Moxalactam, doxycycline, minocycline, and clinafloxacin displayed the highest activity (> or = 98% susceptibility) . Ticarcillin resistance (75%) was reverted by clavulanate in 25% of strains . Trimethoprim-sulfamethoxazole resistance was 26.2% (> or = 4 {trimethoprim}/76 {sulfamethoxazole} microg/ml) and dropped to 11.1% when an 8/152-microg/ml breakpoint was applied based on its bimodal MIC distribution . Resistance was lower when unique strains were considered, because clonal organisms contribute to resistance. Antimicrob Agents Chemother, 2001 May, 45(5), 1558 - 60 Synergistic interactions between mammalian antimicrobial defense peptides; Yan H et al.; A single animal can express several cationic antimicrobial peptides with different sequences and structures . We demonstrate that mammalian peptides from different structural classes frequently show synergy with each other and selectively show synergy with human lysozyme. Antimicrob Agents Chemother, 2001 May, 45(5), 1450 - 5 Inhibition of intramacrophage growth of Penicillium marneffei by 4-aminoquinolines; Taramelli D et al.; The antimicrobial activities of chloroquine (CQ) and several 4-aminoquinoline drugs were tested against Penicillium marneffei, an opportunistic fungus that invades and grows inside macrophages and causes disseminated infection in AIDS patients . Human THP1 and mouse J774 macrophages were infected in vitro with P . marneffei conidia and treated with different doses of drugs for 24 to 48 h followed by cell lysis and the counting of P . marneffei CFU . CQ and amodiaquine exerted a dose-dependent inhibition of fungal growth, whereas quinine and artemisinin were fungistatic and not fungicidal . The antifungal activity of CQ was not due to an impairment of fungal iron acquisition in that it was not reversed by the addition of iron nitrilotriacetate, FeCl3, or iron ammonium citrate . Perl's staining indicated that CQ did not alter the ability of J774 cells to acquire iron from the medium . Most likely, CQ's antifungal activity is due to an increase in the intravacuolar pH and a disruption of pH-dependent metabolic processes . Indeed, we demonstrate that (i) bafilomycin A1 and ammonium chloride, two agents known to alkalinize intracellular vesicles by different mechanisms, were inhibitory as well and (ii) a newly synthesized 4-amino-7-chloroquinoline molecule (compound 9), lacking the terminal amino side chain of CQ that assists in drug accumulation, did not inhibit P . marneffei growth . These results suggest that CQ has a potential for use in prophylaxis of P . marneffei infections in human immunodeficiency virus-infected patients in countries where P . marneffei is endemic. Biochem Biophys Res Commun, 2001 Apr 20, 282(5), 1224 - 8 Purification and characterization of three antifungal proteins from cheeseweed (Malva parviflora); Wang X et al.; Three potent antimicrobial proteins were purified from cheeseweed (Malva parviflora) seeds . These antimicrobial proteins, named CW-3, CW-4, and CW-5, showed different antimicrobial spectrum and potency compared to the two heterologous antimicrobial proteins (CW-1 and CW-2) purified previously . CW-3 and CW-4 possess antimicrobial activities against Phytophthora infestans (Pi), but not Fusarium graminearum (Fg) . A database search indicated that CW-3 shares high homology to cotton vicilin, an abundant seed storage protein . CW-4 shares homology to 2S albumin, another seed storage protein from cotton . CW-5 has antimicrobial activity against Fg, but no activity against Pi was observed at protein concentration up to 50 ppm . Under low salt condition, CW-5 showed potent antimicrobial activity against Fg, but under high salt condition, the antimicrobial activity was drastically diminished . Database search indicated that CW-5 has high homology to a lipid transfer protein from grape . The IC(50) values of the three purified antimicrobial proteins under both low and high salt conditions were determined . The isolation of five antimicrobial proteins for the first time from a single plant source provides further understanding of the plant innate defense system and insight on how plants evolve their complex and complementary antimicrobial system that is important in the early stage of development . Ann Pharmacother, 2001 Apr, 35(4), 480 - 8 Pneumococcal resistance: the treatment challenge; Amsden GW et al.; OBJECTIVE: To review in vitro and in vivo information dealing with pneumococcal antibiotic resistance and provide a review of the incidence, mechanisms, and controversies surrounding this growing problem . The review is also intended to provide clinicians with relevant recommendations on treatment and prevention of this organism . DATA SOURCES AND SELECTION: Primary and review articles were identified by MEDLINE search (1966-August 2000) and through secondary resources such as conference proceedings . All of the articles identified from the data sources were evaluated, and all information deemed relevant was included in this review . DATA SYNTHESIS: The growing incidence and reporting of pneumococcal isolates that are resistant to one or more classes of antibiotics have become a troubling trend that has resulted in significant shifts in treatment . Although clinicians have shifted to a new generation or class of antibiotics when faced with a resistance trend, data with resistant pneumococci show that this may not be necessary . By incorporating the pharmacokinetic and pharmacodynamic data of antimicrobials into the decision-making process, many of the drugs that we have become hesitant to use due to this resistance may still be appropriate if used correctly . CONCLUSIONS: Appropriate dosing of antimicrobials, combined with optimal use of pneumococcal vaccines, will not only prolong the longevity of some agents, but also hopefully slow resistance development. Z Naturforsch {C}, 2001 Jan-Feb, 56(1-2), 49 - 52 New semisynthetic antimicrobial labdane-type diterpenoids derived from the resin "ladano" of Cistus creticus; Kalpoutzakis E et al.; The antimicrobial activity of fifteen semisynthetic labdane-type diterpenes derived from the two major natural compounds 3 and 4 of the resin "ladano" of Cistus creticus is reported . The chloroethyl carbamidic esters 15 and 20 showed the strongest antimicrobial activity against Gram(+), Gram(-) bacteria and pathogenic fungi. Z Naturforsch {C}, 2001 Jan-Feb, 56(1-2), 106 - 10 Mariannaepyrone--a new inhibitor of thromboxane A2 induced platelet aggregation; Fabian K et al.; Mariannaeapyrone ((E)-2-(1,3,5,7-tetramethyl-5-nonenyl)-3,5-dimethyl-6-hydroxy-4H-pyran-4-one) is a new fungal metabolite isolated from fermentations of the common mycophilic deuteromycete Mariannaea elegans . The chemical structure of the 4-pyrone was determined by spectroscopic techniques . Mariannaeapyrone is a selective inhibitor of the thromboxane A2 induced aggregation of human platelets, whereas only weak cytotoxic and antimicrobial effects could be observed. Biochemistry, 2001 Apr 3, 40(13), 3810 - 6 The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment; Sawai MV et al.; Human beta-defensin-2 (HBD-2) is a member of the defensin family of antimicrobial peptides . HBD-2 was first isolated from inflamed skin where it is posited to participate in the killing of invasive bacteria and in the recruitment of cells of the adaptive immune response . Static light scattering and two-dimensional proton nuclear magnetic resonance spectroscopy have been used to assess the physical state and structure of HBD-2 in solution . At concentrations of < or = 2.4 mM, HBD-2 is monomeric . The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta-sheet with strands 2 and 3 in a beta-hairpin conformation . A beta-bulge in the second strand occurs at Gly28, a position conserved in the entire defensin family . In solution, HBD-2 exhibits an alpha-helical segment near the N-terminus that has not been previously ascribed to solution structures of alpha-defensins or to the beta-defensin BNBD-12 . This novel structural element may be a factor contributing to the specific microbicidal or chemokine-like properties of HBD-2. Anticancer Res, 2001 Jan-Feb, 21(1A), 275 - 80 In vitro biological activity of prenylflavanones; Shirataki Y et al.; The biological activity of ten prenylflavanones purified from Sophora tomentosa L., and Sophora moorcroftiana Benth . ex Baker (Leguminosae) was investigated . The flavanones with prenyl-, lavandulyl- or geranyl groups on A ring, and two bioactive flavonostilbenes on ring B and stilbene (resveratrol) showed tumor-specific cytotoxic activity, antimicrobial activity, and anti-HIV activity, radical generation, and O2- scavenging activity . There was a positive relationship between radical generation and O2- scavenging activity in these prenylflavanones . These data suggest the medicinal significance of prenylflavanones. J Pept Res, 2001 Mar, 57(3), 240 - 9 A novel bovine lactoferrin peptide, FKCRRWQWRM, suppresses Candida cell growth and activates neutrophils; Ueta E et al.; To identify potent new antifungal agents, the Candida cell growth inhibitory activities of six lactoferrin (Lf) peptides consisting of 6-25 amino acid residues (peptide 1, FKCRRWQWRMKKLGAPSITCVRRAF lactoferricin B; peptide 2, FKCRRWQWRM; peptide 2', FKARRWQWRM; peptide 3, GAPSITCVRRAF; peptide 4, RRWQWR; and peptide 5, RWQWRM) were examined . Of these, peptide 2 strongly suppressed the multiplication of Candida cells, but other peptides showed only weak activities . In two strains of C . albicans, the minimum inhibitory concentration 100 of peptide 2 (17.3+/-2.2 microM and 17.5+/-2.4 microM) was close to that of miconazole (13.0+/-1.7 microM and 13.1+/-1.6 microM) but markedly different from that of amphotericin B (0.52+/-0.09 microM and 0.56+/-0.11 microM) . The suppression of Candida cell growth was additively increased by a combination of peptide 2 with amphotericin B and miconazole . Peptides 1, 3, 4 and 5 and Lf suppressed iron uptake by Candida cells, inversely correlated with their Candida cell growth inhibition activities . However, iron uptake was not inhibited by peptide 2 . In addition, peptide 2 upregulated Candida cell killing activity of polymorphonuclear leukocytes (PMN) increasing their superoxide generation, protein kinase C activity, p38 MAPK activity and the expression of p47phox . These results indicated that the main antimicrobial activity of the Lf peptides is dependent on the N-terminal half of Lf and that the PMN upregulatory activity of peptide 2 and additive function of peptide 2 with antifungal drugs are useful for prophylaxis and control of candidiasis. J Pept Res, 2001 Mar, 57(3), 175 - 87 Synthesis and characterization of the colistin peptide polymyxin E1 and related antimicrobial peptides; Kline T et al.; Two strategies were developed to synthesize the acylated cyclic peptides know as polymyxins . Synthesis of polymyxin E1 and several analogs enabled us to evaluate the minimum inhibitory concentration of individual compounds against Gram-negative bacteria . In this study we also report the first identification of two component peptides in the complex polymyxin fermentation product colistin, a Thr2Ser isoform and an acyl group isomer . Both of these peptides, as well as a known component peptide, Leu7Ile, were similar to polymyxin E1 in potency, suggesting that conservative mutations in the colistin family are functionally inconsequential . In contrast, the acyclic analogs of all of these peptides were inactive, indicating that the characteristic lariat structure of the polymyxins is necessary for antimicrobial activity. Cell Microbiol, 2001 Apr, 3(4), 247 - 54 Recombinant Mycobacterium tuberculosis protein associated with mammalian cell entry; Chitale S et al.; The ability to gain entry and resist the antimicrobial intracellular environment of mammalian cells is an essential virulence property of Mycobacterium tuberculosis . A purified recombinant protein expressed by a 1362 bp locus (mce1) in the M . tuberculosis genome promoted uptake into HeLa cells of polystyrene latex microspheres coated with the protein . N-terminus deletion constructs of Mce1 identified a domain located between amino acid positions 106 and 163 that was needed for this cell uptake activity . Mce1 contained hydrophobic stretches at the N-terminus predictive of a signal sequence, and colloidal gold immunoelectron microscopy indicated that the corresponding native protein is expressed on the surface of the M . tuberculosis organism . The complete M . tuberculosis genome sequence revealed that it contained four homologues of mce (mce1, mce2, mce3, mce4) and that they were all located within operons composed of genes arranged similarly at different locations in the chromosome . Recombinant Mce2, which had the highest level of identity (67%) to Mce1, was unable to promote the association of microspheres with HeLa cells . Although the exact function of Mce1 is still unknown, it appears to serve as an effector molecule expressed on the surface of M . tuberculosis that is capable of eliciting plasma membrane perturbations in non-phagocytic mammalian cells. Br J Dermatol, 2001 Apr, 144(4), 769 - 74 Mixed immunobullous disease of childhood: a good response to antimicrobials; Powell J et al.; BACKGROUND: Immunobullous diseases are uncommon in childhood . In contrast to adults, the most commonly seen is IgA-mediated chronic bullous disease of childhood (CBDC), while IgG-mediated bullous pemphigoid (BP), cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) are rare . We have demonstrated both IgG and IgA autoantibodies to basement membrane zone target antigens in eight children with 'mixed immunobullous disease of childhood' . OBJECTIVES: To elucidate whether a dual antibody response makes these patients distinct regarding their presentation, immunopathology, course and prognosis . METHODS: We compared the eight children showing the double antibody response with 62 children with CBDC, BP, CP and EBA in whom only one antibody isotype was demonstrated . Clinical information at presentation, clinical course and response to treatment were recorded, and immunoblotting and direct and indirect immunofluorescence (IF) were performed . RESULTS: Six of the eight patients presented with clinical features of CBDC . In two others, it was uncertain whether they had CBDC or BP . Seven of the eight demonstrated a dual antibody response on indirect IF and three on direct IF . Immunoblotting revealed a variety of epidermal and dermal target antigens (BP230, BP180, 97-kDa protein and laminin 5) . Five of the eight responded well to dapsone, two to sulphonamides, and one to systemic erythromycin alone . The clinical course was not protracted . Five are in remission 1-4 years following treatment, and three still have active disease suppressed by treatment after 6 months-2 years . CONCLUSIONS: Although we do not know why these children have 'mixed immunobullous disease' (the dual antibody response), our results indicate that the presence of IgA is associated with a good response to treatment with antimicrobials (dapsone, sulphonamides, erythromycin), and the clinical course is no more protracted than that found in children with a single antibody response. Am J Med Genet, 2001 Apr 22, 100(2), 145 - 51 Deficiency of the specific granule proteins, R-binder/transcobalamin I and lactoferrin, in plasma and saliva: a new disorder; Lin JC et al.; The mechanisms of hereditary deficiency of R binder, which originates in neutrophils and exocrine gland epithelium, are unknown and may be multiple . This led us to examine if defective R binder synthesis also involves proteins that colocalize with it in neutrophil-specific granules and exocrine epithelial cells and may be under common regulatory control . Stored plasma and saliva samples from five unrelated R binder-deficient patients and control subjects were assayed for R binder, lactoferrin, cationic antimicrobial protein-18, neutrophil gelatinase-associated lipocalin, gelatinase, lysozyme, and myeloperoxidase . One patient, patient A, had lactoferrin levels below the limits of detection in both plasma and saliva in addition to his R binder deficiency . Although his deficiency involved lactoferrin as well, he had no history of predisposition to infection . PCR amplification of his R binder gene promoter region and the beginning of the first exon revealed no DNA abnormalities . His son and the son of his equally deficient brother, both presumptive heterozygotes, had mild deficiency of both R binder and lactoferrin . The results show that R binder deficiency exists in at least two forms . One, presumably the less common of the two forms, is the new hereditary entity described here, which is characterized by deficiency of more than one specific granule protein in both plasma and saliva . Despite this more widely distributed absence of the proteins than is found in congenital specific granule deficiency, infection posed no clinical problem in the affected patient . Eur J Immunol, 2001 Apr, 31(4), 1066 - 75 Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells; Niyonsaba F et al.; Antimicrobial peptides, human beta-defensins (hBD-1/-2), and LL-37 (a peptide of human cathelicidin CAP18) are predominately expressed at epithelial tissues, where they participate in the innate host defense by killing invading microorganisms . In this study, to investigate the interactions between epithelial cell-derived antimicrobial peptides and mast cells, we evaluated the effects of hBD-1/-2 and LL-37 on mast cell functions using rat peritoneal mast cells . hBD-2 and LL-37 but not hBD-1 induced histamine release and intracellular Ca(2+) mobilization, and hBD-2 was more potent than LL-37 . Interestingly, histamine release and intracellular Ca(2+) mobilization elicited by hBD-2 and LL-37 were markedly suppressed by BAPTA-AM (an intracellular Ca(2+) chelating agent), pertussis toxin and U-73122 (a phospholipase C inhibitor) . In addition, among the peptides examined, only hBD-2 significantly induced PGD(2) production, which was abolished by indomethacin (cyclooxygenase-1/-2 inhibitor) but not NS-398 (cyclooxygenase-2 inhibitor), suggesting that hBD-2-induced PGD(2) production is mediated by cyclooxygenase-1 . Likewise, the PGD(2) production was suppressed by pertussis toxin and U-73122 . These observations suggest that hBD-2 and LL-37 stimulate mast cells to mobilize intracellular Ca(2+) and release histamine or generate PGD(2) in a G protein-phospholipase C-dependent manner . Thus, hBD-2 and LL-37 may have modulatory effects on inflammatory reactions. Allergy, 2001, 56 Suppl 67, 43 - 4 Plant food allergens homologous to pathogenesis-related proteins; Ebner C et al.; In general, pathogenesis-related (PR) proteins are expressed by plants in response to stress conditions like infection, exposure to certain chemicals, wounding and environmental conditions . In some plant tissues, however, PR proteins are constitutively expressed, e.g . in pollens or fruits, tissues that are more likely to be attacked (by insects or fungi) or exposed to atmospheric conditions (e.g . UV irradiation) . PR proteins display multiple effects within the plant and possess antimicrobial activity, and can thus be regarded as a part of the plant's defense system . Analyzing known amino acid sequences and functions of characterized (cloned) food allergens, it is remarkable that many of these molecules can be classified as PR proteins . Many PR proteins are stable at low pH, and display considerable resistance to proteases, requirements to act as food allergens . According to sequence characteristics and their enzymatic or biologic activity, PR proteins can be divided into 14 groups . Seven of these 14 groups contain proteins with allergenic properties, six groups contain food allergens. J Rheumatol, 2001 Mar, 28(3), 601 - 3 Comparison of viral antibodies in 2 groups of patients with fibromyalgia; Wittrup IH et al.; OBJECTIVE: The etiologies of fibromyalgia (FM) are unknown . In some cases an acute onset following a flu-like episode is described; in other cases patients report slowly developing disease . We previously found increased prevalence of enterovirus IgM antibodies in patients with acute onset of FM compared to healthy controls . We looked for differences in antimicrobial IgM antibodies in acute versus nonacute onset FM . METHODS: Two well defined, comparable groups of patients with FM (acute 19, nonacute 20) were studied for antibodies in serum to an array of viruses including IgM antibodies . RESULTS: In most viruses no IgM antibodies were found . However, about 50% of the patients with acute FM onset had IgM antibodies against enterovirus compared to only 15% of the slow onset patients . CONCLUSION: The higher prevalence of IgM antibodies against enterovirus in patients with acute onset of FM may indicate a difference in the etiology or the immune response in these patients. Nihon Kokyuki Gakkai Zasshi, 2001 Jan, 39(1), 12 - 6 {Beta-defensins in plasma and bronchoalveolar lavage fluid in patients with non-tuberculous mycobacterium infection}; Ashitani J et al.; We measured the levels of beta-defensin 1 and 2 (HBD-1, 2), novel antimicrobial peptides in plasma and in bronchoalveolar lavage fluid (BALF) from patients with with non-tuberculous mycobacterium infection (NTM) . Plasma HBD-2 levels in NTM patients before treatment were higher than those in the controls, while the HBD-1 levels were similar to the control levels . High levels of HBD-2, but not of HBD-1, in BALF were also observed in NTM patients . In NTM, a positive correlation was found between HBD-2 levels in BALF and plasma, and also between HBD-2 and IL-1 beta levels in BALF . NTM patients with cavities or ectasia on chest radiography had higher HBD-2 levels in BALF than those without . Plasma HBD-2 levels in NTM patients were markedly decreased after successful treatment, while those of patients with an intractable mycobacterium infection maintained the same high plasma HBD-2 levels as those before treatment . These findings suggest that HBD-2 may participate in the host defense and plasma HBD-2 levels may reflect disease activity in pulmonary NTM. Chest, 2001 Apr, 119(4), 1131 - 7 Plasma and BAL fluid concentrations of antimicrobial peptides in patients with Mycobacterium avium-intracellulare infection; Ashitani J et al.; STUDY OBJECTIVES: To investigate the roles of human alpha-defensin (HAD), human beta-defensin (HBD)-1, and HBD-2, novel antimicrobial peptides, in patients with Mycobacterium avium-intracellulare infection (MAI) . PATIENTS: The study included 25 patients (10 men) with MAI who visited our hospital between June 1998 and August 1999 . MEASUREMENTS AND RESULTS: In patients with pulmonary MAI, we measured HAD and HBD-1, and HBD-2 levels in plasma and in BAL fluid (BALF) by radioimmunoassay . Plasma concentrations of HAD and HBD-2 in those patients were higher than those in control subjects, whereas HBD-1 levels were similar to those in the control subjects . High levels of HAD and HBD-2, but not HBD-1, also were observed in the BALF of MAI patients . There was a positive correlation between HAD and interleukin (IL)-8 concentrations in the BALF of patients with MAI . BALF HBD-2 concentrations also correlated positively with those of plasma HBD-2 and BALF IL-1 beta in MAI patients . Patients with cavity formation on the chest roentgenogram had higher HAD and HBD-2 levels in their BALF than those of patients without cavity formation . Treatment with clarithromycin combined with two or three other antibiotics, including ethambutol, rifampicin, ofloxacin, or ciprofloxacin, for at least 6 months resulted in a significant fall in plasma HBD-2 concentrations in responders, but not in nonresponders . CONCLUSION: Our findings suggest that HAD and HBD-2 may participate in host defense and local remodeling of the respiratory tract in patients with MAI and that plasma HBD-2 levels may be a useful marker of disease activity in patients with pulmonary MAI. Fitoterapia, 2001 Mar, 72(3), 298 - 300 Antimicrobial activity of Harpullia ramiflora; Khan MR et al.; The methanol extracts of Harpullia ramiflora, leaves, flowers, stem and root barks were partitioned (petrol, dichloromethane, ethyl acetate) . In respect to crude extracts, all fractions demonstrated broader spectrum and higher levels of antibacterial activity . The ethyl acetate fraction of the flowers exhibited the highest activity . No activity was shown against the tested moulds. Fitoterapia, 2001 Mar, 72(3), 286 - 7 Antimicrobial activity of Anacardium occidentale bark; Akinpelu DA; Anacardium occidentale bark 60% methanolic extract exhibited antimicrobial activity against 13 out of 15 bacterial isolates at a concentration of 20 mg/ml. Fitoterapia, 2001 Mar, 72(3), 281 - 3 Antimicrobial activity of Omalanthus nervosus; Khan MR et al.; The ethanol extracts of Omalanthus nervosus leaves, stem and root barks, were partitioned (petrol, dichloromethane, ethyl acetate) . In respect to crude extracts, all fractions demonstrated broader spectrum and higher levels of antibacterial activity, ethyl acetate fractions being in all cases the more active . No fraction was active against tested moulds. J Control Release, 2001 Apr 28, 71(3), 251 - 9 Novel periodontal drug delivery system for treatment of periodontitis; Bromberg LE et al.; A conceptually novel periodontal drug delivery system (DDS) is described that is intended for treatment of microbial infections associated with periodontitis . The DDS is a composite wafer with surface layers possessing adhesive properties, while the bulk layer consists of antimicrobial agents, biodegradable polymers, and matrix polymers . The wafers contain poly(lactic-co-glycolic acid) as the main bioerodible component used in the bulk layer and ethyl cellulose applied as a matrix polymer enabling diffusion-controlled release . Starch and other polymers in combination with AgNO(3) serve as coatings adhesive to the teeth . In vitro experiments demonstrate that the wafers are capable of zero-order release of antimicrobial agents such as silver nitrate, benzylpenicillin, and tetracycline, for over 4 weeks. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 348 - 53 New disinfection and sterilization methods; Rutala WA et al.; New disinfection methods include a persistent antimicrobial coating that can be applied to inanimate and animate objects (Surfacine), a high-level disinfectant with reduced exposure time (ortho-phthalaldehyde), and an antimicrobial agent that can be applied to animate and inanimate objects (superoxidized water) . New sterilization methods include a chemical sterilization process for endoscopes that integrates cleaning (Endoclens), a rapid (4-hour) readout biological indicator for ethylene oxide sterilization (Attest), and a hydrogen peroxide plasma sterilizer that has a shorter cycle time and improved efficacy (Sterrad 50). Emerg Infect Dis, 2001 Mar-Apr, 7(2), 319 - 22 Building communication networks: international network for the study and prevention of emerging antimicrobial resistance; Richet HM et al.; The global nature of antimicrobial resistance and the failure to control the emergence of resistant organisms demand the implementation of a global surveillance program involving both developed and developing countries . Because of the urgent need for infection control interventions and for rapid distribution of information about emerging organisms, we initiated the International Network for the Study and Prevention of Emerging Antimicrobial Resistance (INSPEAR) . Its main objectives are to serve as an early warning system for emerging antimicrobial-drug resistant pathogens, to facilitate rapid distribution of information about emerging multidrug-resistant pathogens to hospitals and public health authorities worldwide, and to serve as a model for the development and implementation of infection control interventions. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 286 - 92 Economic impact of antimicrobial resistance; McGowan JE Jr; One reason antimicrobial-drug resistance is of concern is its economic impact on physicians, patients, health-care administrators, pharmaceutical producers, and the public . Measurement of cost and economic impact of programs to minimize antimicrobial-drug resistance is imprecise and incomplete . Studies to describe and evaluate the problem will have to employ new methods and be of large scale to produce information that is broadly applicable. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 231 - 3 Antiseptic technology: access, affordability, and acceptance; Boyce JM; Factors other than antimicrobial activity of soaps and antiseptic agents used for hand hygiene by health personnel play a role in compliance with recommendations . Hand hygiene products differ considerably in acceptance by hospital personnel . If switching from a nonmedicated soap to an antiseptic agent or increased use of an existing antiseptic agent for hand hygiene prevented a few more infections per year, additional expenditures for antiseptic agents would be offset by cost savings. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 205 - 7 Preventing infections in non-hospital settings: long-term care; Nicolle LE; Infection concerns in long-term care facilities include endemic infections, outbreaks, and colonization and infection with antimicrobial-drug resistant microorganisms . Infection control programs are now used in most long-term care facilities, but their impact on infections has not been rigorously evaluated . Preventive strategies need to address the changing complexity of care in these facilities, e.g., the increased use of invasive devices . The anticipated increase in the elderly population in the next several decades makes prevention of infection in long-term care facilities a priority. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 200 - 4 Ventilator-associated pneumonia or not? Contemporary diagnosis; Mayhall CG; Ventilator-associated pneumonia (VAP) is pneumonia in patients who have been on mechanical ventilation for > or =48 hours . VAP is most accurately diagnosed by quantitative culture and microscopy examination of lower respiratory tract secretions, which are best obtained by bronchoscopically directed techniques such as the protected specimen brush and bronchoalveolar lavage . These techniques have acceptable repeatability, and interpretation of results is unaffected by antibiotics administered concurrently for infection at extrapulmonary sites as long as antimicrobial therapy has not been changed for <72 hours before bronchoscopy. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 188 - 92 Controlling antimicrobial resistance in hospitals: infection control and use of antibiotics; Weinstein RA; Antimicrobial-drug resistance in hospitals is driven by failures of hospital hygiene, selective pressures created by overuse of antibiotics, and mobile genetic elements that can encode bacterial resistance mechanisms . Attention to hand hygiene is constrained by the time it takes to wash hands and by the adverse effects of repeated handwashing on the skin . Alcohol-based hand rubs can overcome the time problem and actually improve skin condition . Universal glove use could close gaps left by incomplete adherence to hand hygiene . Various interventions have been described to improve antibiotic use . The most effective have been programs restricting use of antibiotics and computer-based order forms for health providers. Biochemistry, 2001 Apr 17, 40(15), 4531 - 8 Determination of the disulfide structure of sillucin, a highly knotted, cysteine-rich peptide, by cyanylation/cleavage mass mapping; Qi J et al.; The disulfide structure of sillucin, a highly knotted, cysteine-rich, antimicrobial peptide, isolated from Rhizomucor pusillus, has been determined to be Cys2--Cys7, Cys12--Cys24, Cys13--Cys30, and Cys14--Cys21 by disulfide mass mapping based on partial reduction and CN-induced cleavage enabled by cyanylation . The denatured 30-residue peptide was subjected to partial reduction by tris(2-carboxyethyl)phosphine hydrochloride at pH 3 to produce a mixture of partially reduced sillucin species; the nascent sulfhydryl groups were immediately cyanylated by 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate . The cyanylated species, separated and collected during reversed phase high-performance liquid chromatography, were treated with aqueous ammonia, which cleaved the peptide chain on the N-terminal side of cyanylated cysteine residues . The CN-induced cleavage mixture was analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry before and after complete reduction of residual disulfide bonds in partially reduced and cyanylated species to mass map the truncated peptides to the sequence . Because the masses of the CN-induced cleavage fragments of both singly and doubly reduced and cyanylated sillucin are related to the linkages of the disulfide bonds in the original molecule, the presence of certain truncated peptide(s) can be used to positively identify the linkage of a specific disulfide bond or exclude the presence of other possible linkages. Bioorg Med Chem Lett, 2001 Apr 9, 11(7), 887 - 90 Synthesis of tetrocarcin derivatives with specific inhibitory activity towards Bcl-2 functions; Kaneko M et al.; Tetrocarcin A was recently identified as an inhibitor of the anti-apoptotic function of Bcl-2 . We synthesized novel tetrocarcin derivatives in order to increase their selective inhibitory activity against Bcl-2 . It was found that 21-acetoxy-9-glycosyloxy derivatives had potent Bcl-2 inhibitory activity without significant antimicrobial activity. Ned Tijdschr Geneeskd, 2001 Mar 24, 145(12), 557 - 63 {Periodontitis: a hidden chronic infection}; van Winkelhoff AJ et al.; Periodontitis is a chronic inflammatory disease of the tooth supporting tissues which has a prevalence of 35% in the adult population . Risk factors are dental plaque, calculus, smoking, diabetes mellitus, stress and genetic traits . In parallel with chronic intestinal inflammatory diseases and stomach cancer, gene polymorphisms in the interleukin-I gene family are associated with severity of periodontitis . Periodontitis is usually painless . Symptoms of the disease are bleeding, redness and swelling of the gums, suppuration and migration of teeth . Halitosis may be present . Treatment of periodontitis involves supra- and subgingival mechanical debridement, oral hygiene instruction and surgical elimination of residual deepened and bleeding pockets on indication . Microbiological testing can be used to select patients who may benefit from additional systemic antimicrobial therapy . Periodontal lesions may act as a portal of entry for dissemination of periodontal bacteria into the blood stream, which may result in extraoral infections . For this reason it is recommended to include diagnosis of periodontitis in focal examination . Associations have been documented between periodontitis and cardiovascular diseases, arthritis and premature low birth weight infants. Rev Clin Esp, 2001 Jan, 201(1), 21 - 4 {Guidelines for antibiotic prophylaxis of bacterial endocarditis in patients undergoing dental therapy}; Carmona IT et al.; The objective of the present work was to know the guidelines of antibiotic prophylaxis in bacterial endocarditis used in different spanish health centers . A general dental practitioner asked orally in 50 Cardiology and/or Internal Medicine departments throughout Spain which prophylaxis should be administered to a patient with a mitral valve prosthesis before a dental extraction . The results obtained showed that only 36 (72%) departments used the latest prophylactic guidelines recommended by the American Heart Association or the British Society for Antimicrobial Chemotherapy . Among penicillin allergic patients the antibiotic of choice was erythromycin (60%) followed by clindamycin (28%), although administered at very different dosages (11 and 3, respectively) . Only in 44% of the surveyed departments did the guidelines for allergic and non allergic patients correspond to the recommended protocol by the same study group . The controversy generated regarding the prophylactic indications for bacterial endocarditis might partially account for the results obtained in this study. Crit Care Med, 2001 Apr, 29(4 Suppl), N135 - 42 Is there a role for antibiotic cycling in the intensive care unit? Kollef MH. Antibiotic resistance of bacterial pathogens has emerged as one of the most important issues facing critical care practitioners . Resistance of many commonly encountered bacterial species is increasing and has been associated with greater administration of inadequate antimicrobial therapy to patients within intensive care units . This has resulted in greater patient morbidity, higher mortality rates, and increased healthcare costs . Methods to reduce antimicrobial resistance have focused on increasing adherence to infection control practices and improving antibiotic utilization . Antibiotic cycling is a strategy to reduce antimicrobial resistance by withdrawing an antibiotic or antibiotic class from use and subsequently reintroducing it at a later point in time . The main goal of cycling is to allow resistance rates for specific antibiotics to decrease, or at least remain stable, when their use is periodically eliminated from the intensive care unit. Crit Care Med, 2001 Apr, 29(4 Suppl), N121 - 7 Antimicrobial management measures to limit resistance: A process-based conceptual framework; DeLisle S et al.; To curb the trend toward increasingly resistant microorganisms, we must at least ensure that antibiotics are used in accordance with the best available scientific evidence . Here we review the control and streamlining measures aimed at optimizing the use of antibiotics, placing an emphasis on their demonstrated effectiveness in the intensive care unit environment . Because of their wide variety, the measures have been organized along the process of choosing, dosing, delivering, and then adjusting the initial antibiotics according to the culture results . By clarifying the range of options available, this process-based conceptual framework assists in best adapting a creative mixture of control measures to a particular healthcare system . The framework also facilitates the overview of a proposed multidisciplinary antibiotic management program, thereby helping to secure the administrative and local provider support necessary for its implementation and continued improvement. Crit Care Med, 2001 Apr, 29(4 Suppl), N108 - 13 Intensive care unit antimicrobial resistance and the role of the pharmacist; Ibrahim KH et al.; Over the past 20 yrs, pharmacists have successfully integrated their services and expertise to gain acceptance as full members of pediatric, surgical, medical, and intensive care unit (ICU) patient care teams . The pharmacists' training in pharmacology, pharmacokinetics, pharmacodynamics, and pharmacoeconomics complements the expertise of other members of the patient care team . Generally, a strong background in infectious diseases and critical care also provides a focal point for clinical pharmacy service intervention . Although practitioners often focus on issues exclusively related to their specific hospital or ICU, the issues surrounding antibiotic resistance are more global and societal in nature . Medical, surgical, and pharmaceutical practices inside the hospital and ICU extend their influence into the community . Customs and practices of daily living in our society coupled with use of agents capable of altering microbial flora impact our hospital and ICU when patients from the community are admitted . The misuse of antibiotics and the lack of effective infection control programs are often identified as key components in the perpetuation of these phenomena . The focus for the pharmacist and the ICU team must be on the optimization of antibiotic use and infection control guidelines . This review will address the many issues that surround the appropriate use of antibiotics and what role the pharmacist can play in ensuring the optimal use of infection control measures in the ICU and hospital. Crit Care Med, 2001 Apr, 29(4 Suppl), N87 - 91 Using information systems technology to improve antibiotic prescribing; Bailey TC et al.; The selection of antimicrobial agents in the hospital setting is still a largely manual task and, therefore, fraught with the potential for error . This includes the choice of agents, dosage regimens, and monitoring for response and toxicity . The authors describe current and future strategies to use information technology to improve the process of antimicrobial selection and to avoid dosing errors and contraindicated drug combinations . The possible role of decision support in preventing the emergence of resistance is also discussed. Crit Care Med, 2001 Apr, 29(4 Suppl), N64 - 8 Increasing prevalence of antimicrobial resistance in intensive care units; Fridkin SK; The unique nature of the intensive care unit (ICU) environment makes this part of the hospital a focus for the emergence and spread of many antimicrobial-resistant pathogens . There are ample opportunities for the cross-transmission of resistant bacteria from patient to patient, and patients are commonly exposed to broad-spectrum antimicrobial agents . Rates of resistance have increased for most pathogens associated with hospital-acquired infections among ICU patients, and rates are almost universally higher among ICU patients than non-ICU patients . Likewise, ICU patients hospitalized longer (i.e., >7 days) are two- to three-fold more likely to be infected with a pathogen possessing an antimicrobial-resistant phenotype of concern . However, there are many opportunities to prevent the emergence and spread of these resistant pathogens through improved use of established infection control measures (patient isolation, handwashing, glove use, and appropriate gown use) and implementation of a systematic review of antimicrobial use . (Crit Care Med 2001; 29{Suppl.}: N64-N68) J Biol Chem, 2001 Jun 22, 276(25), 22875 - 82 Epub 2001 Apr 05. Circular proteins in plants: solution structure of a novel macrocyclic trypsin inhibitor from Momordica cochinchinensis; Felizmenio-Quimio ME et al.; Much interest has been generated by recent reports on the discovery of circular (i.e . head-to-tail cyclized) proteins in plants . Here we report the three-dimensional structure of one of the newest such circular proteins, MCoTI-II, a novel trypsin inhibitor from Momordica cochinchinensis, a member of the Cucurbitaceae plant family . The structure consists of a small beta-sheet, several turns, and a cystine knot arrangement of the three disulfide bonds . Interestingly, the molecular topology is similar to that of the plant cyclotides (Craik, D . J., Daly, N . L., Bond, T., and Waine, C . (1999) J . Mol . Biol . 294, 1327-1336), which derive from the Rubiaceae and Violaceae plant families, have antimicrobial activities, and exemplify the cyclic cystine knot structural motif as part of their circular backbone . The sequence, biological activity, and plant family of MCoTI-II are all different from known cyclotides . However, given the structural similarity, cyclic backbone, and plant origin of MCoTI-II, we propose that MCoTI-II can be classified as a new member of the cyclotide class of proteins . The expansion of the cyclotides to include trypsin inhibitory activity and a new plant family highlights the importance and functional variability of circular proteins and the fact that they are more common than has previously been believed . Insights into the possible roles of backbone cyclization have been gained by a comparison of the structure of MCoTI-II with the homologous acyclic trypsin inhibitors CMTI-I and EETI-II from the Cucurbitaceae plant family. Infect Immun, 2001 May, 69(5), 3248 - 54 Calprotectin expression by gingival epithelial cells; Ross KF et al.; Calprotectin, a heterodimer of MRP8 and MRP14 with antimicrobial properties, is found in the cytosol of neutrophils, monocytes, and human gingival keratinocytes . During inflammation of the oral mucosa, the expression of immunoreactive calprotectin appears upregulated . Given the possible cell sources, we sought to learn if epithelial cells upregulate calprotectin in response to proinflammmatory agents . First, human gingival keratinocytes were maintained in primary culture until senescence . At each passage, cells were harvested and analyzed for quantitative expression of MRP8 and MRP14 subunit mRNA by RNase protection assays and calprotectin complex by enzyme-linked immunosorbent assay . Calprotectin expression was constitutive in the primary gingival keratinocytes, but calprotectin-specific mRNA and protein tended to increase as the cells neared senescence . To test whether calprotectin expression was inducible, immortalized gingival keratinocyte cultures were treated for 2 to 4 h with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) . As a positive control for inducible expression, immortalized keratinocytes were incubated with phorbol myristate acetate (PMA) (50 ng/ml) for 24 h . Incubation with PMA stimulated increased expression of MRP8 and MRP14 mRNA within 2 h, peaking within 5 h . MRP8- and MRP14-specific mRNA expression by immortalized keratinocytes appeared to be unaffected by LPS or IL-1 beta . In contrast, LPS, IL-1 beta, and PMA each upregulated IL-8 . These data show that calprotectin mRNA is expressed constitutively in cultured keratinocytes, while expression by immortalized cells appears to be independent of the exogenous proinflammatory agents LPS and IL-1 beta. J Pharm Pharmacol, 2001 Mar, 53(3), 283 - 94 Overcoming antimicrobial resistance by targeting resistance mechanisms; Poole K; Three mechanisms of antimicrobial resistance predominate in bacteria: antibiotic inactivation, target site modification, and altered uptake by way of restricted entry and/or enhanced efflux . Many of these involve enzymes or transport proteins whose activity can be targeted directly in an attemptto compromise resistance and, thus, potentiate antimicrobial activity . Alternatively, novel agents unaffected by these resistance mechanisms can be developed . Given the ongoing challenge posed by antimicrobial resistance in bacteria, targeting resistance in this way may be our best hope at prolonging the antibiotic era. Eur J Cancer, 2001 Mar, 37(5), 597 - 604 Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma; Twelves C et al.; Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.) . Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v . 5-FU/LV . The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles . Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV . In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV . In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events . Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression . Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients . Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV . In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events . As anticipated with an oral home-based therapy patients receiving capecitabine needed more frequent unscheduled home, day care, office and telephone consultations with physicians . In the light of clinical results from the phase III trial demonstrating increased efficacy in terms of response rate, equivalent time to progression (TTP) and survival (OS), and a superior safety profile, the results from this medical resource assessment indicate that capecitabine treatment of colorectal cancer patients results in a substantial resource use saving relative to the Mayo Clinic regimen of 5-FU/LV . This benefit is derived principally from the avoidance of hospital visits for i.v . drug administration, less expensive drug therapy for the treatment of toxic side-effects, and fewer treatment-related hospitalisations required during the course of therapy for adverse drug reactions in comparison to patients treated with 5-FU/LV. Braz J Infect Dis, 2001 Feb, 5(1), 13 - 20 Epub 2001 Aug 03. Community acquired pneumonia among pediatric outpatients in Salvador, Northeast Brazil, with emphasis on the role of pneumococcus; Nascimento-Carvalho CM et al.; Pneumonia is one of the leading causes of hospitalization and death among children in developing countries, and mortality due to pneumonia has been associated with S . pneumoniae infection . This investigation was designed to describe the antimicrobial susceptibility and serotype patterns of pneumococcal strains recovered from the blood of children with community-acquired pneumonia (CAP) and to assess the clinical findings of pneumococcal bacteremic patients with pneumonia . In a 26 month prospective study, blood cultures were obtained as often as possible from children (<16 years of age) diagnosed with CAP in two emergency rooms . Antimicrobial drug susceptibility tests and serotyping were performed when pneumococcus was identified . We studied 3,431 cases and cultured blood samples from 65.5% of those . Pneumococcus was recovered from 0.8% of the blood samples . The differences in age, somnolence, wheezing and hospitalization among children with and without pneumococcal bacteremia were statistically significant . Pneumococcal bacteremia was age-related (mean 1.63 +/- 1.55; median 0.92) and associated with somnolence and hospitalization among children with CAP . One strain was recovered from pleural fluid . Penicillin resistance was detected in 21.0% (4/19) of the strains at an intermediate level, whereas 63.0% of the strains were resistant to trimethoprim-sulfamethoxazole . The most common serotypes were 14 and 6B, and these serotypes included the resistant strains . Eight of our 18 isolates from blood were of types included in the heptavalent conjugate pneumococcal vaccine, recently licensed in the USA. Cancer Res, 2001 Mar 15, 61(6), 2434 - 8 RGD-Tachyplesin inhibits tumor growth; Chen Y et al.; Tachyplesin is an antimicrobial peptide present in leukocytes of the horseshoe crab (Tachypleus tridentatus) . In this study, a synthetic tachyplesin conjugated to the integrin homing domain RGD was tested for antitumor activity . The in vitro results showed that RGD-tachyplesin inhibited the proliferation of both cultured tumor and endothelial cells and reduced the colony formation of TSU prostate cancer cells . Staining with fluorescent probes of FITC-annexin V, JC-1, YO-PRO-1, and FITC-dextran indicated that RGD-tachyplesin could induce apoptosis in both tumor and endothelial cells . Western blotting showed that treatment of cells with RGD-tachyplesin could activate caspase 9, caspase 8, and caspase 3 and increase the expression of the Fas ligand, Fas-associated death domain, caspase 7, and caspase 6, suggesting that apoptotic molecules related to both mitochondrial and Fas-dependent pathways are involved in the induction of apoptosis . The in vivo studies indicated that the RGD-tachyplesin could inhibit the growth of tumors on the chorioallantoic membranes of chicken embryos and in syngenic mice. J Periodontol, 2001 Feb, 72(2), 265 - 73 Management of soft tissue ridge deformities with acellular dermal matrix . Clinical approach and outcome after 6 months of treatment; Batista EL Jr et al.; BACKGROUND: Soft tissue ridge defects often hamper ideally shaped artificial crowns and are basically treated using autogenous soft tissue grafts or alloplastic materials . These approaches present disadvantages such as the necessity of creating additional surgical fields to harvest the graft and the requirement of primary closure, which may reduce ridge height . This investigation evaluated the use of acellular dermal matrix (ADM) in the treatment of soft tissue ridge defects . METHODS: Eight patients, non-smokers with non-contributory medical history, provided 18 sites corresponding to missing teeth in the anterior maxillary arch . The ideal horizontal gain (desired gain) was waxed up in study casts, which served as templates for construction of modified acrylic stents with orthodontic wires . These stents served as references for ideal horizontal gain and also as fixed reference points for further evaluation . The distance from the orthodontic wire to the buccal plate of the defect also represented its baseline horizontal component . Vertical variations were evaluated with another stent and, in this case, no desired gain was considered . After raising partial-thickness flaps, the ADM material was rehydrated and folded to fill the defect and reproduce the desired gain . Flaps were sutured with no tension, and part of the material was intentionally left exposed to avoid pressure on the incision line and prevent height loss . Patients used local and systemic antimicrobials, and the sutures were removed at 7 days . RESULTS: Evaluations were carried out at 30 days, and 3 and 6 months, and all sites healed uneventfully . Neither infection nor significant pain was reported by the patients, and the material was covered by tissue at about 21 days . Mean horizontal gain of 1.72 +/- 0.59 mm (58.5%) at 6 months and mean shrinkage of 1.22 +/- 0.46 mm (41.4%) were observed . There was a mean improvement in vertical gain of only 0.61 +/- 0 . 77 mm, although 66 . 7% of the treated sites showed a 1 to 2 mm gain . Clinically, the total gain in the subjects was very effective and matched the receptor tissues nicely . CONCLUSIONS: ADM may be a suitable material for the treatment of soft tissue ridge deformities due to its biocompatibility, color matching, and horizontal gain . Additional controlled, comparative trials are necessary to establish its advantages and potential compared to autogenous soft tissue techniques. Am J Infect Control, 2001 Apr, 29(2), 124 - 5 Antibacterial efficacy of triclosan-incorporated polymers; Kalyon BD et al.; Triclosan (2, 4, 4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antimicrobial agent, routinely used in various personal care products.(1) It is also incorporated into polymers through melt-mixing, with the aim of providing persistent antibacterial action on the surface of the polymer.(2,3) Such triclosan-incorporated polymers can be promoted for hospital use as fabric seat covers, tables, chairs, and clothing . We assessed the antibacterial efficacy of triclosan-incorporated polymer disks against 2 bacteria cultured in liquids in contact with the polymer . In spite of the relatively high concentrations of triclosan in the polymer, only some initial slowing of the bacterial growth rates was observed, followed by the absence of an antibacterial effect over extended periods . The triclosan at the surface of the disks dissolves into the liquids, and the rest of the triclosan, immobilized in the disks, does not contribute to the antibacterial effectiveness of triclosan-incorporated polymer . In light of recent studies, which have shown that triclosan acts on a specific target within the bacterial lipid synthesis pathway, triclosan-incorporated polymers may provide the ideal setting for resistant strains of bacteria to grow and thus should be used selectively in hospital environments. Br J Oral Maxillofac Surg, 2001 Apr, 39(2), 134 - 7 Role of antimicrobials in third molar surgery: prospective, double blind,randomized, placebo-controlled clinical study; Sekhar CH et al.; AIM: To test the efficacy of two dosing regimens of antimicrobial prophylaxis during the removal of impacted lower third molars . DESIGN: Double blind, prospective, placebo-controlled trial . SETTING: Teaching hospital, India . SUBJECTS: 151 patients aged 19-36 having impacted lower third molars removed . METHODS: Random allocation into three groups: placebo (n= 34), metronidazole 1g orally, 1 hour preoperatively (n= 44), or metronidazole 400mg orally eight hourly for 5 days postoperatively (n= 47) . Patients were recalled on the sixth postoperative day for assessment of pain scores on the second and sixth days, swelling, differences in mouth opening between preoperative and the sixth postoperative day, and the state of the wound . RESULTS: There were no significant differences in the outcome between the three groups (P= 0.09) . CONCLUSION: Antimicrobial prophylaxis does not seem to reduce morbidity after removal of lower third molars . Br J Oral Maxillofac Surg, 2001 Apr, 39(2), 122 - 6 Necrotizing fasciitis of odontogenic origin in Ibadan, Nigeria; Obiechina AE et al.; We reviewed eight patients with necrotizing fasciitis of odontogenic origin . There were three women and five men, mean age 58 (range 46-72), and none had any associated medical condition such as diabetes . All cases had symptoms of toothache for a mean duration of 34 days (range 26-42) before they sought treatment . Infection originated in the molar teeth region, and initially presented as an odontogenic or periodontal abscess . The clinical features of necrotizing fasciitis became apparent only after the superficial fascia had been invaded . The transient unusually reddish hue for a dark skin might be explained by the fact the deep fascia and muscles were affected before the superficial fascia and skin . Necrosis of the skin began in the submandibular region and progressed downwards . The necrotic area was less than the extent of infection . Antimicrobial treatment, debridement, and fasciotomy improved healing . Delay before appropriate treatment had an adverse affect on outcome, and one patient died . Clin Pharmacokinet, 2001, 40(2), 125 - 34 A retrospective analysis of pharmacokinetic-pharmacodynamic parameters as indicators of the clinical efficacy of ceftizoxime; Sanchez-Navarro A et al.; OBJECTIVE: To analyse the relationship between a series of estimated pharmacokinetic-pharmacodynamic parameters and the reported efficacy of ceftizoxime . DESIGN: Retrospective literature search and analysis using different correlation models . METHODS: The following parameters were calculated for each group of patients included in the study from the simulated plasma concentration curves corresponding to the dosage regimen administered: (i) peak concentration at steady state divided by the minimum inhibitory concentration (CmaxSS/MIC); (ii) the time that the plasma drug concentration exceeded the MIC scaled to 24 hours at steady state {(tSS)24h > MIC}; (iii) the total area under the concentration-time curve over 24 hours at steady state divided by the MIC {(AUC(SS))24h/MIC}; and (iv) the AUC at steady state for the period of time that the concentration is above the MIC over a period of 24 hours divided by the MIC {(AUIC(SS))24h} . A univariate correlation analysis was performed considering efficacy {rate (%) of clinical cure or bacterial eradication} as the dependent variable and the pharmacokinetic-pharmacodynamic parameter as the independent variable, using linear and nonlinear models . RESULTS: (tSS)24h > MIC was the only parameter that was statistically correlated with efficacy, the linear model being the best choice among the 4 relationship approaches tested . A biased frequency distribution of reported efficacy data constricts the correlation analysis to a narrow range of efficacy and hinders interpretation of the results . CONCLUSIONS: The reporting of cases with low efficacy rates as well as those with high efficacy rates, including information on patient idiosyncrasies and the infecting organisms, would be of great help in performing retrospective analyses of the use of antimicrobial agents, leading to the optimisation of therapy with this type of drug in clinical practice. World Health Organ Tech Rep Ser, 2000, 895, 1 - 61 The use of essential drugs; WHO Expert Committee; This report presents the recommendations of a WHO Expert Committee responsible for updating and revising the Model List of Essential Drugs . The first part describes the criteria for the selection of essential drugs and pharmaceutical dosage forms, and includes discussion of quality assurance, pharmacovigilance, drug utilization studies, drug information and educational activities, and future developments of the model list . In the light of increasing resistance to antimicrobials, particular attention is drawn to the need for and use of reserve antimicrobials . The second part presents the eleventh revised model list, together with details of the changes that have been made, a glossary of terms and an alphabetical index of all the drugs included. Int J Infect Dis, 2001, 5(1), 3 - 8 Successful shortening from seven to four days of parenteral beta-lactam treatment for common childhood infections: a prospective and randomized study; Peltola H et al.; OBJECTIVES: To explore whether 4-day parenteral beta-lactam therapy is as effective as 7-day therapy for children hospitalized for parenteral antimicrobials . METHODS: A series of patients aged 3 months to 15 years who fulfilled strict criteria for bacterial pneumonia, other respiratory infections, sepsis-like infections, and other acute infections were prospectively randomized to receive parenteral penicillin or cefuroxime randomly for 4 or 7 days . Besides blood and throat cultures, the etiology was searched by serology for 23 different agents . RESULTS: Of 154 children analyzed, a probable etiology was established in 96 . Of those, a bacterial infection, with or without concomitant viral infection, was disclosed in 80% and 94% in the 4-day and 7-day treatment groups, respectively; pneumococcus being the commonest agent . There was one possible treatment failure in the 4-day group, but with a questionable relation to the short course . Three patients in the 4-day and two in the 7-day group underwent treatment changes, or were rehospitalized within 30 days . All children recovered entirely . CONCLUSIONS: Shortening parenteral beta-lactam treatment to 4 days in infections for which most parenteral antimicrobials are instituted, is not only safe, but reduces costs, is ecologically sound, and minimizes the risks of nosocomial infections and other adverse effects of treatment. Aliment Pharmacol Ther, 2001 Apr, 15(4), 487 - 92 Comparative efficacy of new investigational agents against Helicobacter pylori; Osato MS et al.; BACKGROUND: Emergence of antibiotic resistant Helicobacter pylori has necessitated the identification of alternate therapies for the treatment of this infection . AIM: To assess the in vitro efficacy of two investigational agents: DMG-MINO CL 344 (a N,N-dimethylglycylamido derivative of minocycline), and davercin, a cyclic carbonate of erythromycin A as compared to older antibiotics (clarithromcyin, azithromycin, minocycline, tetracycline, ofloxacin, ciprofloxacin, cefixime) against clinical isolates of H . pylori . METHODS: Testing was performed using the agar dilution method approved by the NCCLS subcommittee on antimicrobial susceptibility testing, Helicobacter pylori working group . Under these guidelines, Mueller-Hinton agar containing 5% aged sheep blood was used . All incubations were done under CampyPak Plus conditions for 72 h at 37 degrees C . The drug concentrations in the agar ranged from 0.016 to 16 microg/mL . Twenty-one clarithromycin-resistant and 16 clarithromycin-susceptible clinical isolates of H . pylori obtained from patients with duodenal ulcer were used . H . pylori ATCC 43504 was used as the control in all determinations . RESULTS: Against clarithromycin susceptible isolates, all antimicrobial agents except the fluoroquinolones were highly effective . Against clarithromycin-resistant H . pylori, the MIC50/MIC90 values showed that the tetracyclines and cefixime were the most efficacious agents . The fluoroquinolones and macrolides were ineffective . Macrolide cross-resistance was detected . CONCLUSION: Macrolide cross-resistance prevents the use of this entire class of antimicrobials when clarithromycin resistance is present . Tetracyclines and cefixime are possible alternative agents for the treatment of H . pylori infection in these patients. Biochemistry, 2001 Apr 10, 40(14), 4211 - 21 Three-dimensional structure of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes; Trabi M et al.; Most mammalian defensins are cationic peptides of 29-42 amino acids long, stabilized by three disulfide bonds . However, recently Tang et al . (1999, Science 286, 498-502) reported the isolation of a new defensin type found in the leukocytes of rhesus macaques . In contrast to all the other defensins found so far, rhesus theta defensin-1 (RTD-1) is composed of just 18 amino acids with the backbone cyclized through peptide bonds . Antibacterial activities of both the native cyclic peptide and a linear form were examined, showing that the cyclic form was 3-fold more active than the open chain analogue {Tang et al . (1999) Science 286, 498-502} . To elucidate the three-dimensional structure of RTD-1 and its open chain analogue, both peptides were synthesized using solid-phase peptide synthesis and tert-butyloxycarbonyl chemistry . The structures of both peptides in aqueous solution were determined from two-dimensional (1)H NMR data recorded at 500 and 750 MHz . Structural constraints consisting of interproton distances and dihedral angles were used as input for simulated-annealing calculations and water refinement with the program CNS . RTD-1 and its open chain analogue oRTD-1 adopt very similar structures in water . Both comprise an extended beta-hairpin structure with turns at one or both ends . The turns are well defined within themselves and seem to be flexible with respect to the extended regions of the molecules . Although the two strands of the beta-sheet are connected by three disulfide bonds, this region displays a degree of flexibility . The structural similarity of RTD-1 and its open chain analogue oRTD-1, as well as their comparable degree of flexibility, support the theory that the additional charges at the termini of the open chain analogue rather than overall differences in structure or flexibility are the cause for oRTD-1's lower antimicrobial activity . In contrast to numerous other antimicrobial peptides, RTD-1 does not display any amphiphilic character, even though surface models of RTD-1 exhibit a certain clustering of positive charges . Some amide protons of RTD-1 that should be solvent-exposed in monomeric beta-sheet structures show low-temperature coefficients, suggesting the possible presence of weak intermolecular hydrogen bonds. Cas Lek Cesk, 2001 Mar 1, 140(4), 104 - 7 {Hyperbaric oxygen therapy in non-healing wounds and defects} }; Dolezal V; Our study presents effects of the hyperbaric inhalation oxygenotherapy in the treatment of ischaemic diseases of lower extremities and chronic refractory problem wounds . Hyperbaric oxygenotherapy (HO) has antioedemic effect, it stimulates collagen synthesis, formation of granular tissue, and antimicrobial capacity of leukocytes . It also stimulates formation of new blood vessels, which is important namely in tissue hypoxia accompanying microangiopathy of the diabetic foot . HO should be administered as soon as possible after the diagnosis is fixed . Treatment should be done in co-operation with various specialists: surgeons, diabetologists, angiologists, orthopaedic surgeons and specialist on the hyperbaric medicine . First evaluation of HO effects should be done after 15 expositions to HO . If effects are negative, treatment should continue till 25 expositions . If effects are still negative, the treatment should terminate . As a part of complex treatment, HO can prevent high amputations, decrease the duration of hospitalisation and thus economise the whole therapy . Similar results were described in several clinical studies from different developed industrial countries. Clin Infect Dis, 2001 Apr 15, 32(8), 1172 - 7 Epub 2001 Apr 02. Brucellosis in pregnant women; Khan MY et al.; Brucella species occasionally cause spontaneous human abortion, but theories regarding whether they do so more frequently than do other infectious pathogens remain controversial . We reviewed 92 pregnant women who presented with acute brucellosis at a Saudi Arabian hospital . From 1983 through 1995, the cumulative incidence of pregnancy and brucellosis was 1.3 cases per 1000 delivered obstetrical discharges . The incidence of spontaneous abortion in the first and second trimesters was 43%, and the incidence of intrauterine fetal death in the third trimester was 2% . Antepartum antimicrobial therapy with cotrimoxazole or cotrimoxazole/rifampin was protective against spontaneous abortion (relative risk, 0.14; 95% confidence interval, 0.06--0.37; P<.0001) . The beneficial effect of treatment occurred in women with febrile illness; vaginal bleeding at presentation usually led to spontaneous abortion . This study demonstrated that the incidence of spontaneous abortion among pregnant women with brucellosis is high and that these women should receive prompt therapy with antimicrobial agents when they present for medical care. J Clin Microbiol, 2001 Apr, 39(4), 1654 - 6 Susceptibility of Arcobacter butzleri, Arcobacter cryaerophilus, and Arcobacter skirrowii to antimicrobial agents used in selective media; Houf K et al.; Several antimicrobial agents used in selective media for the isolation of Arcobacter were found to be inhibitory to strains belonging to this genus . All three species tested were susceptible to colistin and rifampin at concentrations used in selective media . Arcobacter skirrowii was the most susceptible species . 5-Fluorouracil, novobiocin, trimethoprim, and teicoplanin or vancomycin were found to be without any inhibitory effect on the strains tested at concentrations described for the isolation of Arcobacter species. J Clin Microbiol, 2001 Apr, 39(4), 1368 - 77 Chlamydial serology: comparative diagnostic value of immunoblotting, microimmunofluorescence test, and immunoassays using different recombinant proteins as antigens; Bas S et al.; To improve the reliability of the serodiagnosis of Chlamydia trachomatis infections, an immunoblot analysis, a microimmunofluorescence titration, and different immunoassays using synthetic peptides derived from species-specific epitopes in variable domain IV of the major outer membrane protein or recombinant antigens (heat shock protein 70 {hsp70}, hsp60, hsp10, polypeptide encoded by open reading frame 3 of the plasmid {pgp3}, macrophage infectivity potentiator, and a fragment of the total lipopolysaccharide) were evaluated . Because cross-reactions between chlamydial species have been reported, the microimmunofluorescence tests were also performed with Chlamydia pneumoniae and Chlamydia psittaci used as antigens, and C . pneumoniae-specific antibodies were also determined by immunoassays . Since the presence of antimicrobial antibodies must be interpreted in light of their prevalence in the general population, responses obtained with serum samples from patients with well-defined infection (i.e., with positive urethral or endocervical C . trachomatis DNA amplification) were compared to those obtained with samples from healthy blood donors . The best sensitivity (86%) with a specificity of 81% was obtained for immunoblotting results, when the number of individuals with > or =10 immunoglobulin G (IgG) and/or > or =2 IgM responses to the different C . trachomatis antigens was considered . A 13-kDa antigen was recognized by most of the samples (86% for IgG) from patients with acute urogenital infection but rarely (3%) by those from healthy blood donors (P < 0.0001) . The sensitivity and specificity results obtained for serum antibodies to peptides or recombinant antigens were slightly lower than those results obtained for the number of responses to whole C . trachomatis antigens, which were 76 and 77%, respectively, when IgG responses to both recombinant hsp60 and pgp3 were considered. Appl Environ Microbiol, 2001 Apr, 67(4), 1940 - 4 Genotypic analysis of Escherichia coli strains from poultry carcasses and their susceptibilities to antimicrobial agents; Geornaras I et al.; Plasmid profiling and amplified fragment length polymorphism (AFLP) analysis were used to genotype 50 Escherichia coli strains from poultry carcasses . Thirty different plasmid profiles were evident, and clustering of the AFLP data showed that they were a distinctly heterogeneous group of strains . Susceptibility testing against five antimicrobial agents used in the South African poultry industry showed all strains to be susceptible to danofloxacin and colistin, while the majority (96%) were resistant to two tetracyclines. Int J Antimicrob Agents, 2001 Mar, 17(3), 237 - 40 An in vitro study of the efficacy of rifampicin and minocycline coated umbilical venous catheters; Norton RE et al.; The use of antibiotic coated catheters has been proposed as a means of reducing catheter related sepsis . In this study, an in vitro comparison of bacterial colonisation rates was made between uncoated umbilical venous catheters and catheters coated with rifampicin and minocycline . The following parameters were determined; the direct antimicrobial effect of coated and uncoated catheter segments against a range of organisms associated with line sepsis, the assessment of the decline in antimicrobial activity in coated catheters immersed in plasma and the inhibitory efficacy of the catheters to colonisation over a 28-day period . Minocycline and rifampicin coated umbilical catheters showed a superior inhibitory effect and prevented colonisation with the commoner line-related organisms, when compared with uncoated catheters . The inhibitory effect declined after 14 days in the human plasma . Resistance to colonisation in vitro may not extend beyond 21 days. Int J Antimicrob Agents, 2001 Mar, 17(3), 233 - 6 Evolution of metronidazole and tetracycline susceptibility pattern in Helicobacter pylori at a hospital in Saudi Arabia; Al-Qurashi AR et al.; The association of Helicobacter pylori with chronic gastritis and peptic ulcer disease led to new therapeutic approaches including the use of antibiotics . Recently, resistance of H . pylori to antibiotics has emerged as the major cause of treatment failure . This retrospective analysis was aimed at investigating the development of antimicrobial susceptibility patterns amongst H . pylori strains isolated at King Fahd Hospital of the University, Al-Khobar . Susceptibility patterns obtained using isolates from a pilot study (1987-1988) were compared with those subsequently isolated (1990-1996) . Metronidazole resistance was estimated to be 35.2% in the first period but more than doubled (78.5%) during the second period . Isolates from females showed a higher resistance rate to metronidazole than those from males . Only one strain was tetracycline resistant . The extremely high resistance rate to metronidazole indicates that it may not be very effective for eradication of H . pylori . Tetracycline should prove a useful component of treatment regimens in this geographical region. J Org Chem, 2001 Apr 6, 66(7), 2251 - 64 C(5)-C(5a)-modified bicyclomycins: synthesis, structure, and biochemical and biological properties; Vincent F et al.; Bicyclomycin (1) is a novel antibiotic that targets rho transcription termination factor in Escherichia coli . We have demonstrated that retention of the C(5)-C(5a) exomethylene unit in 1 is not essential for inhibition . In a recent paper we proposed a working model for 1 and rho function and suggested that 1 binds in a cleft with the C(5)-C(5a) exomethylene unit directed toward the dimeric interface of two rho monomers . This report examines the bicyclomycin C(5)-C(5a) structural constraints necessary for retention of rho inhibitory activity . Three classes of C(5)-C(5a)-modified bicyclomycins have been prepared and their inhibitory activities evaluated in the poly C-dependent ATPase and filter disk antimicrobial assays . The first series consisted of 12 analogues (8-19) that contained a C(5a)-unsaturated substituent and possessed C(5E)-geometry . The second set were a pair of C(5a)-substituted C(5E)- and C(5Z)-geometrical isomers (21 and 23) . The final group of compounds consisted of six C(5)-C(5a)-dihydrobicyclomycins (24-28, 34) where the terminal substituent was systematically varied . We find that extending the C(5)-C(5a) double bond with unsaturated substituents provides bicyclomycin derivatives with excellent inhibitory activities in the biochemical assay, and that enhanced inhibitory activity is observed for the C(5E) geometrical isomer compared with its C(5Z) counterpart . Finally, C(5a)-substituted dihydrobicyclomycin inhibitory activity appears to be tightly regulated by the nature and spatial placement of the C(5a)-terminal substituent with respect to the {4.2.2}-bicyclic ring system . The observed biochemical activities for the C(5a)-extended conjugated bicyclomycin derivatives and the (5E) and (5Z) isomers were correlated with a structural model for the 1-rho complex. Protein Expr Purif, 2001 Apr, 21(3), 424 - 31 Production of recombinant bovine lactoferrin N-lobe in insect cells and its antimicrobial activity; Nakamura I et al.; Lactoferrin is a multifunctional, iron-binding glycoprotein found in physiological fluids of mammals . In the present study, a gene encoding the N-terminal half (N-lobe) of bovine lactoferrin was cloned and expressed in cultured insect cells using a baculovirus expression system . One mutation was found in the lactoferrin N-lobe gene, but it resulted in no amino acid substitution . The recombinant lactoferrin N-lobe was secreted into the culture medium and partially purified by means of an immobilized heparin column . The recombinant lactoferrin N-lobe secreted was not glycosylated, but it possessed antimicrobial activity toward Escherichia coli O111 . The recombinant product synthesized and accumulated in the host cells exhibited greater electrophoretic mobility on SDS-PAGE than the secreted product and showed no potency to inhibit the growth of bacteria . It is thought that the product accumulated intracellularly lacks antimicrobial ability due to its degradation in the host cells or due to disruption of the active conformation . J Cutan Med Surg, 2001 Jan-Feb, 5(1), 37 - 42 The efficacy and safety of a combination benzoyl peroxide/clindamycin topical gel compared with benzoyl peroxide alone and a benzoyl peroxide/erythromycin combination product; Leyden JJ et al.; BACKGROUND: Topical clindamycin and benzoyl peroxide have each demonstrated clinical efficacy in the treatment of acne vulgaris . When used in tandem, they promise greater efficacy than either individual agent through their antibacterial and anti-inflammatory effects . OBJECTIVE: To determine the efficacy and safety of combination benzoyl peroxide/ clindamycin compared with benzoyl peroxide or benzoyl peroxide/erythromycin in the treatment of acne . METHODS: In this randomized, 10-week, multicenter, single-blind trial, 492 patients with moderate to moderately severe acne were treated twice daily with 5% benzoyl peroxide/1% clindamycin, 5% benzoyl peroxide, or 5% benzoyl peroxide/3% erythromycin and assessed every 2 weeks . RESULTS: Compared with benzoyl peroxide, benzoyl peroxide/clindamycin demonstrated significantly greater reductions in inflammatory lesions (p = 0.04) and significantly greater overall improvement as assessed by physicians (p < or = 0.04) and patients (p < 0.001) . Benzoyl peroxide/clindamycin demonstrated a nonsignificant trend for greater efficacy compared to benzoyl peroxide/erythromycin . Dry skin was the most frequent (< or = 7.3%) adverse event with all three therapies . CONCLUSION: Benzoyl peroxide/clindamycin demonstrated improved efficacy and similar tolerability; to benzoyl peroxide used alone and was similar to benzoyl peroxide/ erythromycin, making this combination product an effective alternative antimicrobial therapy for acne. Phytochemistry, 2001 Mar, 56(6), 569 - 76 Phytoecdysteroids in the genus Asparagus (Asparagaceae); Dinan L et al.; Phytoecdysteroids, plant steroids which are analogues of invertebrate steroid hormones, probably contribute to the deterrence of phytophagous invertebrate predators . They also seem to possess antimicrobial activity and several pharmaceutical and medicinal benefits have been ascribed to them . Here . we present a survey of seeds of 16 species of the genus Asparagus (Asparagaceae), including the crop species A . officinalis, for ecdysteroid agonists (including phytoecdysteroids) and antagonists . Seven species were found to contain ecdysteroids with levels ranging from just detectable (A . racemosus and A . sarmentosus) to relatively high (A . laricinus) . RP-HPLC/RIA/bioassay has been used to separate positive extracts of four species (A . falcatus, A . laricinus, A . ramosissimus and A . scandens) and analyse the ecdysteroid profiles . The identities of the major ecdysteroids were confirmed by NP-HPLC . Seeds of A . officinalis do not contain detectable levels of ecdysteroids, but leaves, stems and roots contain low levels (detectable by RIA) . This indicates that A . officinalis retains the genetic capacity to synthesise ecdysteroids and that future strategies could be developed for enhanced protection of asparagus spears through elevated ecdysteroid levels. Can Fam Physician, 2001 Mar, 47, 521 - 7 Prescribing practices and attitudes toward giving children antibiotics; Paluck E et al.; OBJECTIVE: To investigate whether overprescribing is common in treatment of pediatric upper respiratory infections and to examine factors that influence prescribing antibiotics for children . DESIGN: A random, stratified sample of practising family physicians was surveyed with a mailed questionnaire . Initial nonresponders were mailed a second questionnaire . SETTING: British Columbia . PARTICIPANTS: A total of 608 general and family physicians . Response rate was 64%; 392/612 surveys were completed . MAIN OUTCOME MEASURES: Physicians' self-reported prescribing practices and knowledge of and attitudes toward using antibiotics for children's upper respiratory tract infections . RESULTS: Relative to treatment guidelines developed for the study, most physicians responded appropriately to the cough (94%) and lobar pneumonia (99.1%) vignettes . More than half the physicians (56.5%) reported they would immediately prescribe antibiotics for tympanic membrane dysfunction, and 79.4% indicated they would prescribe antibiotics for pharyngitis without obtaining a laboratory culture . Approximately 25% of physicians in the study did not believe that prior antibiotic use increased personal risk for acquiring drug-resistant infection, and 23.1% did not believe that antibiotic use was an important factor in promoting resistance in their communities . CONCLUSION: Education in current treatment of pediatric upper respiratory tract illnesses and antimicrobial drug resistance is required . The high response to the questionnaire (64%) and the many requests from physicians to receive the project's educational materials (45%) indicate a high level of interest in this subject. Am J Hematol, 2001 May, 67(1), 1 - 5 Clinical and pathologic findings in 52 consecutively autopsied cases with multiple myeloma; Oshima K et al.; We studied clinical features and pathologic findings in 52 consecutively autopsied patients with multiple myeloma in our center between 1979 and 1998 . Distant extraosseous involvement was found in 33 patients (63.5%) . Thirty-one patients (59.6%) were proven to have infection at autopsy, among which pneumonia was most common site of infection . Amyloidosis was shown in 8 patients . Second malignancies were observed in 4 cases . The three major causes of death were hemorrhage, infection, and renal failure, which accounted for death in approximately 70% of the patients . Advances in the anticancer and antimicrobial chemotherapies might have decreased deaths due to myeloma itself or infection . Vet Pathol, 2001 Mar, 38(2), 230 - 2 Septicemia and peritonitis due to Actinobacillus equuli infection in an adult horse; Patterson-Kane JC et al.; Actinobacillus equuli is a rare cause of peritonitis in adult horses . Septicemia and peritonitis due to A . equuli were diagnosed at necropsy in an 8-year-old Saddlebred mare . The origin of the infection was not known; however, small necrotic colonic mucosal lesions presumed to have been caused by phenylbutazone treatment may have allowed bacterial invasion . A good response to antimicrobial treatment has been documented in the small numbers of previously reported acute cases of peritonitis . Because it is potentially treatable, it is important for pathologists and clinicians to identify horses with A . equuli peritonitis. Commun Dis Public Health, 2000 Dec, 3(4), 305 - 6 Effects of infection control measures on skin of health care workers; Wilkinson SM; A review of patients presenting to a contact dermatitis investigation clinic in 1999 showed that almost half (60/124) of those with occupational hand dermatitis were health care workers . The use of fragrance-free products would be a simple intervention to reduce the prevalence of allergic contact dermatitis without affecting antimicrobial efficacy; other measures are discussed. Commun Dis Public Health, 2000 Dec, 3(4), 234 - 9 PHLS works towards effective interaction with primary care; McNulty CA et al.; The PHLS primary care initiative was set up to develop and maintain links with primary care professionals, including researchers, GP research networks, and primary care groups in order to prioritize research and laboratory service developments . Such collaboration has spawned the development of antibiotic guidance, which has been posted on the Internet, and participation of the PHLS in other infectious disease guidance (for example, Prodigy) . The implementation of the NHS information strategy will further facilitate the development of and access to local and national primary care guidance, laboratory reporting, and participation in surveillance . Primary care professionals identified several main research priorities in an exercise that facilitated collaboration in the development of research projects and grant applications . These priorities are the natural history of infections presenting to GPs, antibiotic resistance, the role of clinical scores and the laboratory in the diagnosis of infection, the importance of patient and professional attitudes in modifying antimicrobial prescribing, and the role of health professionals in community infection control . Current rapid changes in primary care in the new NHS--such as NHS Direct and the establishment of walk-in centres--may affect the surveillance of communicable disease by offering opportunities for improved data collection but also by posing threats to current systems of surveillance. J Biol Chem, 2001 May 25, 276(21), 17823 - 9 Epub 2001 Feb 22. Ponericins, new antibacterial and insecticidal peptides from the venom of the ant Pachycondyla goeldii; Orivel J et al.; The antimicrobial, insecticidal, and hemolytic properties of peptides isolated from the venom of the predatory ant Pachycondyla goeldii, a member of the subfamily Ponerinae, were investigated . Fifteen novel peptides, named ponericins, exhibiting antibacterial and insecticidal properties were purified, and their amino acid sequences were characterized . According to their primary structure similarities, they can be classified into three families: ponericin G, W, and L . Ponericins share high sequence similarities with known peptides: ponericins G with cecropin-like peptides, ponericins W with gaegurins and melittin, and ponericins L with dermaseptins . Ten peptides were synthesized for further analysis . Their antimicrobial activities against Gram-positive and Gram-negative bacteria strains were analyzed together with their insecticidal activities against cricket larvae and their hemolytic activities . Interestingly, within each of the three families, several peptides present differences in their biological activities . The comparison of the structural features of ponericins with those of well-studied peptides suggests that the ponericins may adopt an amphipathic alpha-helical structure in polar environments, such as cell membranes . In the venom, the estimated peptide concentrations appear to be compatible with an antibacterial activity in vivo . This suggests that in the ant colony, the peptides exhibit a defensive role against microbial pathogens arising from prey introduction and/or ingestion. Eur J Med Chem, 1999 Jul-Aug, 34(7-8), 639 - 43 In vitro antimicrobial activity of aromatic diamidines and diimidazolines related to pentamidine; Donkor IO et al.; Geometric isomers of pentamidine analogues were screened for antimicrobial activity in vitro . cis isomers demonstrated good antibacterial activity compared to their trans counterparts . Both isomers were moderately active against opportunistic pathogens that afflict AIDS patients with minimum inhibitory concentrations in the range of 3.12-12.5 microg/mL. Eur J Med Chem, 1999 Jul-Aug, 34(7-8), 575 - 83 Synthesis and anti-Pneumocystis carinii pneumonia activity of novel dicationic dibenzothiophenes and orally active prodrugs; Patrick DA et al.; Dicationic carbazoles have been found to be highly active against a rat model of Pneumocystis carinii pneumonia (PCP) . Unfortunately, amidoxime derivatives, designed as prodrugs, were inactive against PCP even though the corresponding amidines were highly active . In the present work, a series of 2,8- and 3,7-bis cationic dibenzothiophenes was synthesized and assayed for anti-PCP activity . Three of the compounds proved to be more potent and less toxic than a standard anti-PCP drug (pentamidine) when given intravenously . Unlike the carbazoles, a dibenzothiophene amidoxime prodrug given orally reduced the parasite load by more than 99% . While no quantitative correlation was seen between anti-PCP activity and DNA binding, a strong level of DNA binding was found to be necessary for antimicrobial activity. Eur J Biochem, 2001 Apr, 268(7), 2124 - 33 Solution structure of microcin J25, the single macrocyclic antimicrobial peptide from Escherichia coli; Blond A et al.; The three-dimensional solution structure of microcin J25, the single cyclic representative of the microcin antimicrobial peptide class produced by enteric bacteria, was determined using two-dimensional 1H NMR spectroscopy and molecular modeling . This hydrophobic 21-residue peptide exhibits potent activity directed to Gram-negative bacteria . Its primary structure, cyclo(-V1GIGTPISFY10GGGAGHVPEY20F-), has been determined previously {Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M . J., Barthelemy, M., Prigent, Y., Salomon, R.A., Farias, R.N., Moreno, F . & Rebuffat, S . (1999) Eur . J . Biochem., 259, 747-755} . Conformational parameters (3JNHCalphaH coupling constants, quantitative nuclear Overhauser enhancement data, chemical shift deviations, temperature coefficients of amide protons, NH-ND exchange rates) were obtained in methanol solution . Structural restraints consisting of 190 interproton distances inferred from NOE data, 11 phi backbone dihedral angle and 9 chi1 angle restraints derived from the coupling constants and three hydrogen bonds in agreement with the amide exchange rates were used as input for simulated annealing calculations and energy minimization in the program XPLOR . Microcin J25 adopts a well-defined compact structure consisting of a distorted antiparallel beta sheet, which is twisted and folded back on itself, thus resulting in three loops . Residues 7-10 and 17-20 form the more regular part of the beta sheet . The region encompassing residues Gly11-His16 consists of a distorted beta hairpin, which divides into two small loops and is stabilized by an inverse gamma turn and a type I' beta turn . The reversal of the chain leading to the Phe21-Pro6 loop results from a mixed beta/gamma turn . A cavity, in which the hydrophilic Ser8 side-chain is confined, is delimited by two crab pincer-like regions that comprise residues 6-8 and 18-1. J Nat Prod, 2001 Mar, 64(3), 341 - 4 Cortamidine oxide, a novel disulfide metabolite from the New Zealand basidiomycete (mushroom) Cortinarius species; Nicholas GM et al.; Three disulfide metabolites were isolated from the fruiting bodies of the basidiomycete (mushroom) Cortinarius sp., collected in the Catlins, New Zealand . The structures of these compounds were determined as the unsymmetrical disulfide cortamidine oxide (1), 2,2'-dithiobis(pyridine N-oxide) (2), and the symmetrical disulfide 3 . Both 1 and 2 showed significant antimicrobial activity and cytotoxicity . 2,2'-Dithiobis(pyridine N-oxide) (2) and the symmetrical disulfide 3 are assumed to be artifacts of the isolation procedure. Am Fam Physician, 2001 Mar 15, 63(6), 1087 - 98 Antimicrobial resistance: a plan of action for community practice; Hooton TM et al.; Antibiotic resistance was once confined primarily to hospitals but is becoming increasingly prevalent in family practice settings, making daily therapeutic decisions more challenging . Recent reports of pediatric deaths and illnesses in communities in the United States have raised concerns about the implications and future of antibiotic resistance . Because 20 percent to 50 percent of antibiotic prescriptions in community settings are believed to be unnecessary, primary care physicians must adjust their prescribing behaviors to ensure that the crisis does not worsen . Clinicians should not accommodate patient demands for unnecessary antibiotics and should take steps to educate patients about the prudent use of these drugs . Prescriptions for targeted-spectrum antibiotics, when appropriate, can help preserve the normal susceptible flora . Antimicrobials intended for the treatment of bacterial infections should not be used to manage viral illnesses . Local resistance trends may be used to guide prescribing decisions. Adv Dent Res, 1999 Jun, 13, 67 - 72 In vitro models of biological responses to implant microbiological models; Mombelli A; To study the etiology and explore possibilities for the therapy of implant-associated infections, investigators have developed and utilized various in vitro models . Major contributions have come from the non-oral