Intensive Care Med, 2003 Dec, 29(12), 2170 - 3 Epub 2003 Sep 12. Impact of adequacy of initial antimicrobial therapy on the prognosis of patients with ventilator-associated pneumonia; Leroy O et al.; OBJECTIVE: To study the prognostic impact of the appropriateness of initial antimicrobial therapy in patients suffering from ventilator-associated pneumonia (VAP) . DESIGN AND SETTING: Observational cohort from January 1994 to December 2001 in one intensive care unit (ICU) from an university-affiliated, urban teaching hospital . PATIENTS: All 132 consecutive patients exhibiting bacteriologically documented VAP during ICU stay . MEASUREMENTS AND RESULTS: Initial antimicrobial treatment was deemed appropriate when the period from initial VAP diagnosis and subsequent administration of antibiotics was within 24 h and all causative pathogens were in vitro susceptible to at least one of the antibiotics of the regimen . Such a treatment was present in 106 episodes . Fifty-eight patients died . In bivariate analysis an appropriate initial antimicrobial therapy was associated with a significantly lower mortality rate (40% vs . 62%) . In multivariate analysis the three independent factors present upon VAP onset and associated with death were pulmonary involvement of more than a single lobe on chest radiograph, platelet count less than 150000/mm(3), and Simplified Acute Physiology Score II higher than 37 . Appropriate antimicrobial therapy was associated with a nonsignificant trend toward a lower mortality . CONCLUSIONS: In our cohort the mortality rate was lower in patients suffering from VAP when the initial antimicrobial therapy was appropriate . However, such a factor did not appear as an independent prognostic factor. Nephrol Dial Transplant, 2003 Oct, 18(10), 2067 - 73 The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing; Anding K et al.; BACKGROUND: Neutrophil functions in haemodialysis (HD) patients are altered by uraemia and by HD procedure . We investigated details of the neutrophil dysfunction as its nature and origin is not well understood . This is reflected by conflicting results about neutrophil phagocytosis activity and by scarce data on the neutrophil killing capability in HD patients . METHODS: Using a flow-cytometric test system we have measured simultaneously phagocytosis and the production of reactive oxygen species (ROS) of neutrophils and in parallel antimicrobial killing of yeast by neutrophils . 117 whole-blood samples of healthy controls and 50 pre- and 50 post-dialysis samples of HD patients, half of them with diabetes mellitus (DM), have been evaluated . We have constructed a model to account for the dependence on the stimulus-to-cell ratio and obtain means for phagocytosis and killing at different incubation times . RESULTS: (i) HD patients have significantly lower neutrophil killing (20%) than healthy controls . (ii) Dialysis improves the killing capability by 10-15%, after dialysis the killing activity remains significantly (10%) below that of the controls . (iii) The percentage of neutrophils, which exhibit phagocytosis and produce ROS, does not differ significantly between HD patients and healthy controls . (iv) Age has no significant influence on phagocytosis and killing . CONCLUSION: The neutrophil killing capability is reduced in HD patients while the amount of neutrophils that phagocyte and produce ROS remains unchanged . Functional impairment of uraemic neutrophils is therefore mainly a result of their reduced capability to kill microorganisms intracellularly. J Biol Chem, 2003 Nov 28, 278(48), 48485 - 90 Epub 2003 Sep 17. The RuvAB branch migration complex can displace topoisomerase IV.quinolone.DNA ternary complexes; Shea ME et al.; Quinolone antimicrobial drugs target both DNA gyrase and topoisomerase IV (Topo IV) and convert these essential enzymes into cellular poisons . Topoisomerase poisoning results in the inhibition of DNA replication and the generation of double-strand breaks . Double-strand breaks are repaired by homologous recombination . Here, we have investigated the interaction between the RuvAB branch migration complex and the Topo IV.quinolone.DNA ternary complex . A strand-displacement assay is employed to assess the helicase activity of the RuvAB complex in vitro . RuvAB-catalyzed strand displacement requires both RuvA and RuvB proteins, and it is stimulated by a 3'-non-hybridized tail . Interestingly, Topo IV.quinolone.DNA ternary complexes do not inhibit the translocation of the RuvAB complex . In fact, Topo IV.quinolone.DNA ternary complexes are reversed and displaced from the DNA upon their collisions with the RuvAB complex . These results suggest that the RuvAB branch migration complex can actively remove quinolone-induced covalent topoisomerase.DNA complexes from DNA and complete the homologous recombination process in vivo. Ann Intern Med, 2003 Sep 16, 139(6), 463 - 9 The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections; McMahon BJ et al.; BACKGROUND: The relationship between previous antimicrobial treatments and infection with drug-resistant Helicobacter pylori is unknown . OBJECTIVES: To determine whether previous use of antimicrobial agents predicts subsequent antibiotic resistance of H . pylori and whether resistance affects treatment outcome . DESIGN: Retrospective cohort analysis of adults recruited sequentially from a clinical practice . SETTING: A referral hospital in Anchorage, Alaska . PATIENTS: 125 adults infected with H . pylori . MEASUREMENTS: Medical records were reviewed for antimicrobial agents prescribed in the 10 years before diagnosis with H . pylori infection . Antimicrobial susceptibility of H . pylori isolates obtained from endoscopic gastric biopsy was determined by using agar dilution . Cure was determined by using the urea breath test 2 months after antimicrobial treatment . RESULTS: Among the 125 patients, 37 (30%) were found to have H . pylori isolates resistant to clarithromycin and 83 (66%) were found to have H . pylori isolates resistant to metronidazole . Resistance to clarithromycin was associated with previous use of any macrolide antibiotic (P < 0.001), and resistance to metronidazole was associated with previous use of metronidazole (P < 0.001) . The odds of isolates being resistant to clarithromycin increased in relation to the number of courses of macrolides received (P < 0.001) . Among 53 persons treated with clarithromycin-based regimens, treatment failed in 77% of those carrying clarithromycin-resistant H . pylori (10 of 13) and 13% of those with clarithromycin-susceptible strains (5 of 40) (relative risk, 6.2 {95% CI, 1.9 to 37.1}; P < 0.001) . CONCLUSIONS: Previous use of macrolides and metronidazole is associated with H . pylori resistant to these antimicrobial agents . Clarithromycin resistance is associated with a greater risk for failure with clarithromycin-based treatments. Life Sci, 2003 Oct 10, 73(21), 2675 - 85 Effects of moxifloxacin in zymogen A or S . aureus stimulated human THP-1 monocytes on the inflammatory process and the spread of infection; Hall IH et al.; Antimicrobial agents have been reported to exhibit immunomodulatory and anti-inflammatory activities, both in vivo and in vitro (e.g., in human lymphocytes, macrophages and monocytes) . The effects of moxifloxacin on cytokine immunomodulatory mediators, free radical generation and hydrolytic enzyme activities in zymogen A-stimulated human THP-1 monocytes were evaluated . An increase in c-AMP levels, protein kinase C activity, and the release of nitric oxide and hydrogen peroxide with a decrease in pH occurred within the first hour . Further, the effects of moxifloxacin were reduced by agents which blocked the oxygen burst, lysosome-phagosome fusion, and the energy generation within the cell . After 4 h, there was a decrease in NAG and cathepsin D activities, lipid peroxidation and the release of pro-inflammatory cytokines . These data indicate that moxifloxacin may modify the acute-phase inflammatory responses through inhibition of cytokine release in monocytes . Moxifloxacin inhibited the release of TNFalpha, IL-1, IL-6, and IL-8 in a concentration-dependent manner across a range of 0.004 to 4 microg/mL . After 4 h, there was a decrease in the release of these cytokines, thus interfering with the inflammation process to reduce infection and its spread . The effects of moxifloxacin appear initially to activate monocytes to kill bacteria through the innate immune process by releasing ROS and lysosomal hydrolytic enzymes as well as phagocytosis of the organism . At a later time the bacteria are killed through a Bacterialstatic mechanism of protein synthesis inhibition and there is a reversal of the effects of moxifloxacin on cytokine release, free radical generation and hydrolytic enzymes so that lipid peroxidation and tissue destruction by the infection process is suppressed. Farmaco, 2003 Sep, 58(9), 951 - 9 An investigation of the biological effect of structural modifications of isothiosemicarbazones and their cyclic analogues; Maccioni E et al.; Several arylideneisothiosemicarbazones and arylidenehydrazothiazoles have been synthesised to obtain new antimicrobial agents . Their activity against both bacteria and fungi has been tested and some interesting informations about their biological activity have been obtained. Farmaco, 2003 Sep, 58(9), 875 - 81 Synthesis, X-ray crystal structure and biological properties of acetylenic flavone derivatives; Artali R et al.; The reactions of iodoflavone with 3-methyl-3-hydroxybut-1-yne and 3-methylbut-3-en-2-yne are described and the antimicrobial and cytotoxic activities of the obtained compounds have been tested . The molecular structures of 6-(3-hydroxy-3-methylbut-1-ynyl)-flavone (1a) and 6-(3-methylbut-3-en-1-ynyl) flavone (1b) have been determined by X-ray crystallography . The planar configuration of the two compounds has been attributed to intramolecular hydrogen bond interactions . In 1a, the presence of the hydroxyl group determines a dimeric arrangement of the molecules . In both compounds in the crystal state, molecular stacking has been observed. Farmaco, 2003 Sep, 58(9), 639 - 50 Quinoxaline chemistry . Part 16 . 4-substituted anilino and 4-substituted phenoxymethyl pyrrolo{1,2-a}quinoxalines and N-{4-(pyrrolo{1,2-a}quinoxalin-4-yl)amino and hydroxymethyl}benzoyl glutamates . Synthesis and evaluation of in vitro biological activity; Alleca S et al.; Twenty eight pyrrolo{1,2-a}quinoxalines bearing at position 4 various substituents related to the moieties present in classical and non classical antifolic agents were prepared and evaluated in vitro for antiproliferative activity . In an in vitro screening performed at NCI, several compounds emerged as potent antiproliferative agents at concentrations ranging between 10 and 100 microM . Interestingly, some of these compounds proved active also against bovine and murine DHFR (Farmaco 53 (1998) 480) . More recently, a compound of classical antifolate type has been reported to be a potent inhibitor of hDHFR in vitro (Farmaco 58 (2003) 51) . We then synthesized new derivatives that, in our hands, were endowed with in vitro antiproliferative activities as low as 3.4 microM against a panel of cell lines derived from hematological and solid tumours . In addition, a complete screening of cytotoxicity, antiretroviral HIV-1 and antimicrobial activity has been carried out. Biochem Biophys Res Commun, 2003 Oct 3, 309(4), 879 - 84 Indolicidin, a 13-residue basic antimicrobial peptide rich in tryptophan and proline, interacts with Ca(2+)-calmodulin; Sitaram N et al.; Indolicidin, ILPWKWPWWPWRR-NH(2), a short 13-residue antimicrobial and cytolytic peptide characterized from bovine neutrophils, has the calmodulin-recognition 1-5-10 hydrophobic pattern (indicated by amino acids in bold), is cationic, and thereby fulfills the requirements to interact with calmodulin . Hence, we have investigated the calmodulin-binding properties of indolicidin . Indolicidin interacted with calmodulin with fairly high affinity in a Ca(2+)-dependent manner . However, when bound, the peptide did not adopt helical conformation . Indolicidin also inhibited calmodulin-stimulated phosphodiesterase activity with IC(50) values in the nanomolar range . Replacement of either the proline residues of indolicidin with alanines or tryptophan residues with phenylalanines did not affect binding to calmodulin . However, these replacements had distinctive effects on the conformations of the bound peptides . While the alanine analog of indolicidin adopted predominantly alpha-helical conformation, the phenylalanine analog remained largely unordered . Differences in the ability of these analogs to inhibit the calmodulin-stimulated phosphodiesterase activity were observed . While the alanine analog was capable of inhibiting the activity with IC(50) values comparable to that of indolicidin, the phenylalanine analog did not inhibit the activity . Our results indicate that ability to adopt amphiphilic alpha-helical structure is not a prerequisite for binding to calmodulin and also binding does not necessarily result in inhibition of calmodulin-stimulated enzyme activities. Int J Antimicrob Agents, 2003 Sep, 22(3), 205 - 10 Mobile genes coding for efflux-mediated antimicrobial resistance in Gram-positive and Gram-negative bacteria; Butaye P et al.; Efflux mechanisms that account for resistance to a variety of antimicrobial agents are commonly found in a wide range of bacteria . Two major groups of efflux systems are known, specific exporters and transporters conferring multidrug resistance (MDR) . The MDR systems are able to remove antimicrobials of different classes from the bacterial cell and occasionally play a role in the intrinsic resistance of some bacteria to certain antimicrobials . Their genes are commonly located on the bacterial chromosome . In contrast, the genes coding for specific efflux systems are often associated with mobile genetic elements which can easily be interchanged between bacteria . Specific efflux systems have mainly been identified with resistances to macrolides, lincosamides and/or streptogramins, tetracyclines, as well as chloramphenicol/florfenicol in Gram-positive and Gram-negative bacteria . In this review, we focus on the molecular biology of antimicrobial resistance mediated by specific efflux systems and highlight the association of the respective resistance genes with mobile genetic elements and their distribution across species and genus borders. Curr Infect Dis Rep, 2003 Oct, 5(5), 416 - 425 Bite Wound Infections; Myers JP; Patients with mammalian bite wounds account for hundreds of thousands of emergency department, urgent care center, and physician office visits in the United States each year . The types of wounds encountered by physicians range from insignificant scratches to life-threatening neck and facial injuries . Infectious complications of bite wounds are common, and the consequences of these infections are significant and sometimes disabling . This article reviews the infectious complications of cat, dog, and human bite wounds . The prevention of tetanus and rabies virus infection, the appropriate antimicrobial treatment of bacterial infections, and the frequent need for surgical consultation and intervention are emphasized. J Med Chem, 2003 Sep 25, 46(20), 4240 - 3 Oxidosqualene cyclase inhibitors as antimicrobial agents; Hinshaw JC et al.; Small-molecule oxidosqualene cyclase (OSC) inhibitors were found to be effective in assays against cloned OSC-like enzymes from human pathogens . A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture . Selectivity for the microorganisms in preference to mammalian cells was observed. Wien Med Wochenschr, 2003, 153(15-16), 349 - 53 {From pneumonic infiltration to parapneumonic effusion--from effusion to pleural empyema: internal medicine aspects of parapneumonic effusion development and pleural empyema}; Domej W et al.; Infectious processes cause the majority part of all clinically relevant pleural effusions which frequently complicate the course of pneumonia . The assessment of an inflammatory effusion requires a careful history, physical examination, imaging techniques and clinical workup . The presence of polymorphonuclear leukocytes, high LDH-activity (> 200 U/L) and protein level (> 3 g/dL) in a pleural effusion indicates acute inflammation . An effusion is usually called empyema, when large numbers of neutrophils form thick, turbid exudates within preexisting body cavities . A thoracic empyema may occur as a result of primary or secondary pleural pathologies and in most cases involves infection with bacteria, frequently provided by progressing pneumonia . There are several therapeutic options for treatment of parapneumonic effusions and of thoracic empyemata, respectively . Optimal therapeutic management and antimicrobial medication to the infected pleural space depend in part on the stage of the empyema at presentation . Treatment can vary from a conservative medical approach in uncomplicated or small parapneumonic effusions to invasive surgical interventions in fibroprulent or organizational stages of empyema . Empyemata usually progress from a parapneumonic exudative stage (stage I), when the fluid is still sterile, with low leukocyte counts, low LDH, physiological pH, and normal glucose, to the fibropurulent {figures: see text} stage (stage II) with high leukocyte counts, high LDH activity, low pH, and low glucose, and finally to the organizational stage (stage III), in which fibroblasts convert fibrin strands into inelastic membranes . Pleural peels and pockets may compartmentalize the viscous empyematous fluid and can cause serious restrictive ventilatory impairment . Each patient must be individually evaluated to determine the nature of the exudate and the stage of the pleural space infection . Due to its high mortality rate (5%) a thoracic empyema requires prompt treatment . Diagnostic thoracentesis and withdrawal of liquid for the microbiological, cytological and biochemical analysis is urgently recommended in all cases to assess severity of the disease and the likelihood of a complicated or uncomplicated course, and to select the most appropriate treatment option. Wien Med Wochenschr, 2003, 153(15-16), 345 - 8 {Are new antibiotics in therapy of respiratory tract infections necessary?}; Haberl R et al.; Increasing worldwide antibacterial resistance among respiratory pathogens, especially S . pneumoniae, are an emerging problem in the treatment of respiratory tract infections . In some areas penicillin-resistant S . pneumoniae increased to 80% and macrolide-resistance and MLSb-resistance are an evolving problem . In addition, increasing resistance to quinolones has been documented in Hong Kong and in Spain . One way to combat increasing resistance is the development of new antimicrobial drugs . However, the practice of just changing one drug for another without also altering poor prescribing habits merely results in different resistance issues . In the long-term, to prevent increasing resistance, clinicians must be aware of restrictive antibiotic prescription and adequate dosages. Wien Med Wochenschr, 2003, 153(15-16), 342 - 4 {Pharmacokinetics of antibiotics in inflamed and healthy lung tissue}; Tomaselli F et al.; The pharmacokinetic profile of antibiotics at the site of antiinfective action is one of the most important determinants of drug response, since it correlates the antimicrobial effect . Up to now, only limited information on the lung tissue pharmacokinetics of antibiotic agents has been available . The aim of in-vivo microdialysis is to measure antibiotic penetration into the extracellular space fluid of normal or pneumonic human lung parenchyma . The lung penetration of cefpirom in elective thoracic surgery and piperacillin in septic thoracic surgery, substances with low protein binding, was measured . Intra-, or postoperatively, respectively, microdialysis probes were inserted into normal or pneumonic lung tissue and into healthy skeletal muscle to obtain reference values . Serum and microdialysis samples were collected at 20-minute intervals for at last 8 hours . The intrapulmonary concentrations of the antibiotics exceeded the minimum inhibitory concentrations (MIC) for most relevant bacteria for 4-6 hours . The procedure was well tolerated by all patients and no adverse events or microdialysis-associated side effects were observed . This microdialysis technique enabled continuous tissue pharmacokinetic measurement of free, unbound anti-infective agents in the lung tissue, even in pneumonia. Arzneimittelforschung, 2003, 53(8), 590 - 9 Antimicrobial activity of N-acylphenothiazines and their influence on lipid model membranes and erythrocyte membranes; Motohashi N et al.; The antibacterial activity and influence on lipid model membranes and erythrocyte membranes of 24 N-acylphenothiazines and trifluoperazine were studied . (1) Among 24 phenothiazines, the antimicrobial activity of amino maleates was the highest . (2) The influence of phenothiazines on model liposome and erythrocyte membranes was studied using N-phenyl-1-naphthylamine (NPN) as fluorescence probe . From the three types of phenothiazine substitution (H, Cl, CF3) at position 2, CF3-phenothiazines were the most effective in the interaction with liposomal membranes . (3) As measured by the polarization degree of 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence, the alteration of membrane fluidity induced by CF3-phenothiazines was the biggest . Surprisingly, phenothiazines induced stomatocytic shape alterations (invaginations) in erythrocytes and at higher concentrations, also hemolysis of erythrocytes was observed . (4) The microcalorimetic measurements of influence of phenothiazines on thermal behaviour of synthetic lipid systems confirmed the previously obtained results . The main transition temperature and enthalpy of transition of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were significantly modified by CF3-phenothiazines, suggesting their penetration of the lipid bilayer . Above results show that phenothiazine maleates were generally more effective than other phenothiazines used in this study. Antibiot Khimioter, 2003, 48(4), 27 - 34 {Efficacy of various antimicrobial agents in the treatment of epidemic typhoid fever}; Makhnev MV; During superepidemic of a typhoid fever in Tadjikistan the efficiency of application in clinics and of 14 antimicrobial agents representing almost all basic chemical classes was investigated . Remarkable variation of frequency and type of S . typhi resistance to these preparations up to epidemic and especially in its process was demonstrated . The absence of absolute (100%) efficacy of the investigated agents in vivo and in vitro was shown . The reasons of low efficacy of etiotropic treatment of the patients with typhoid fever are analysed. Bone Marrow Transplant, 2003 Oct, 32(7), 709 - 14 Nontuberculous mycobacterial infections in Chinese hematopoietic stem cell transplantation recipients; Au WY et al.; Between 1995 and 2002, nine cases of nontuberculous mycobacterium (NTM) were isolated from 462 allogeneic stem cell transplant (SCT) recipients (1.9%), and none from 139 autologous cases . They included three cases each of Mycobacterium fortuitum and M . chelonae, and single cases of M . scrofalaceum, M . gordonnae and M . avium complex . Seven cases were respiratory, including five cases requiring treatment, and two involved infected catheters and vascular conduits . Compared with nine cases of mycobacterium tuberculosis (MTB) isolated in the same period, NTM isolation occurred later after HSCT and involved more unrelated donors . Important risk factors for NTM infection included significant aGVHD (P=0.043), leukemia relapse (P=0.022), MUD and mismatch SCT (P<0.001) and existence of BO (P<0.001) . Coinfection with aspergillus was common . Invasive NTM disease required prolonged antimicrobial treatment in five cases due to M . fortuitum and M . chelonae . With better MTB prophylaxis, intensive immunosuppression and better awareness, NTM has become an emerging threat in oriental allogeneic HSCT recipients . The cutoff between colonization and infection, and the threshold for starting treatment is unclear . NTM isolation is a marker for severe immunosuppression and poor prognosis . When there is doubt over species identity or extent of infection, broad-spectrum cover may be prudent. APMIS, 2003 Jul-Aug, 111(7-8), 715 - 24 Dendritic cells as inducers of antimicrobial immunity in vivo; Sundquist M et al.; Models of infection have provided important insight into the function of dendritic cells (DC) in vivo . Several microbial products induce DC maturation via Toll-like receptors, a process that is crucial for the ability of DC to initiate adaptive immune responses . Splenic DC have also been shown to produce IL-12 during infection in vivo . This DC-derived IL-12 might be important to skew T cell responses towards Th1 . Microbial infections also induce changes in the DC populations of lymphoid organs, often in a subset-specific manner, manifested as an accumulation and redistribution of DC . Furthermore, data are emerging pointing at an absolute requirement of DC in priming of naive T cells in vivo. Oral Dis, 2003, 9 Suppl 1, 63 - 70 Use of antimicrobial agents during supportive periodontal therapy; Venezia E et al.; Individual susceptibility to periodontal breakdown involves an interplay of genes, periodontal pathogens and other modulating factors . Anti-infective treatment, which includes oral hygiene measures, mechanical debridement, pharmacologic intervention and surgery, has been shown to be effective in arresting the progression of periodontal disease . Nevertheless, due to the chronic nature of the disease, susceptible individuals who are not maintained in a supervised recall program subsequent to the active treatment phase, show signs of recurrent destruction . Supportive periodontal therapy (SPT) is an integral part of periodontal treatment for patients with history of periodontitis, and is needed to prevent recurrence of disease in susceptible individuals . To prevent re-infection with periodontal pathogens, SPT includes elimination of dental plaque and bacteria from the oral cavity, thereby preventing the recurrence of pathogens into the gingival area . For individuals at risk of developing periodontitis, SPT should combine self-performed and professional anti-infective therapy, using mechanical and pharmacological means . The existing evidence suggests that the adjunctive use of antimicrobial pharmacologic therapy during SPT may enhance the results of mechanical debridement . The use of antimicrobials varies between patients, and is dependent on risk assessment and longitudinal monitoring of the clinical status of the periodontium. Oral Dis, 2003, 9 Suppl 1, 45 - 50 Locally delivered antimicrobials for the treatment of chronic periodontitis; Etienne D; The basic treatment of chronic periodontitis is a mechanical debridement of periodontal pockets by scaling and root planing (S/RP) in combination with efficient plaque control . Locally delivered antiseptics (LDA) have been proposed to practitioners and, while subgingival irrigation of antiseptics is still used in clinical practice, the introduction in our therapy of a slow release and sub-gingival delivery of tetracycline has changed the rationale from a mechanical treatment towards a combined therapy for full mouth/sites disinfection . Various antibiotics, antiseptics and resorbable carriers are now proposed with similar targets to arrest disease progression . In chronic periodontitis, LDA cannot be used routinely in combination with S/RP, because of the limited clinical benefit, even if an increased percentage of deep sites may show an improvement . Prospective multicenter studies considering risk factors for disease progression have to be designed to identify patients who may benefit the most from LDA . For non-responding sites or recurrent pockets, the controversies are limited, because a combined S/RP and LDA may avoid the need for surgery . However, the patient cost/benefit ratio needs to be estimated as well as adverse effects in particular antibiotics. Oral Dis, 2003, 9 Suppl 1, 38 - 44 Systemic antimicrobials in the treatment of chronic periodontal diseases: a dilemma; Addy M et al.; The use of systemic antimicrobials in the treatment of acute and chronic periodontal diseases must be viewed as a dilemma . On the one hand, the approach is attractive because of the microbial nature of periodontal diseases but, on the other hand, evidence of benefit of these agents is equivocal for the majority of periodontal diseases and antimicrobials have the potential to cause harm . The disadvantages of systemic antimicrobials can be grouped under the headings of allergic reactions, superinfection, toxicity, drug interactions, patient compliance and, perhaps of most widespread importance, bacterial resistance . Mechanical debridement methods, including drainage of pus for acute periodontal abscesses, should be considered the first line treatment for most periodontal diseases . Systemic antimicrobials should be considered as adjuncts to mechanical debridement methods and, in chronic disease, never used alone as they can predispose to abscess formation . Adjunctive systemic antimicrobials may be considered in acute disease where debridement or drainage of pus is difficult, where there is local spread or systemic upset . In chronic periodontal diseases, adjunctive antimicrobials should be considered in early onset or rapidly progressive disease or in advanced chronic adult disease where mechanical therapies have failed or surgery is not a preferred option . Inadequate oral hygiene and tobacco smoking are contraindications to the use of antimicrobials . The value of systemic antimicrobials, where other systemic risk factors co-exist, has still to be established . The role of microbial diagnosis and sensitivity testing for antimicrobial selection at this time must be questioned. Oral Dis, 2003, 9 Suppl 1, 30 - 7 Microbial shifts after subgingival debridement and formation of bacterial resistance when combined with local or systemic antimicrobials; Quirynen M et al.; Antibiotics have played a major role in the improvement of life expectancy in the last 50 years and have led many to believe that bacterial infections were about to vanish as a disease entity of any importance . Emerging problems resulting from a widespread use of antibiotics have modified the general perception of the capabilities of antimicrobial agents . Over the years, bacteria have become increasingly resistant to formerly potent antimicrobial agents, including some antiseptics . The use of antimicrobials may also disturb the delicate ecological equilibrium of the body, allowing the proliferation of resistant bacteria or non-bacterial micro-organisms . This shift may initiate new infections that are worse than the ones originally treated . No antimicrobial drug is absolutely non-toxic and the use of an agent carries accompanying risks . This paper discusses the development and occurrence of antimicrobial resistance in the subgingival flora towards antiseptics and local or systemic antibiotics and is focussed on the question: how can the outcome of periodontal therapy with/without antimicrobials be improved? Oral Dis, 2003, 9 Suppl 1, 11 - 5 Periodontal diseases: current and future indications for local antimicrobial therapy; Trombelli L et al.; The microbial etiology of gingivitis and periodontitis provides the rationale for use of adjunctive antimicrobial agents in the prevention and treatment of periodontal diseases . Although mechanical removal of supra- and subgingival calcified and non-calcified plaque deposits has been proved effective to control the gingival inflammatory lesions as well as to halt the progression of periodontal attachment loss, some patients may experience additional benefits from the use of systemic or topical antimicrobial agents . Such agents are able to significantly affect supra- and subgingival plaque accumulation and/or suppress or eradicate periodontal pathogenic microflora . Currently, properly selected local antiseptic and systemic antibiotic therapies can provide periodontal treatment that is generally effective, low-risk and affordable . This paper will briefly review the host-related conditions in which the periodontal preventive and therapeutic approaches may be effectively assisted by a local antimicrobial regimen . Potential future indications for adjunctive local antimicrobial therapy will also be discussed. J Huazhong Univ Sci Technolog Med Sci, 2003, 23(2), 203 - 5 Susceptibility of mixed infection of Ureaplasma Urealyticum and Mycoplasma Hominis to seven antimicrobial agents and comparison with that of Ureaplasma Urealyticum infection; Huang C et al.; In order to investigate the susceptibility of mixed infection of Ureaplasma Urealyticum (UU) and Mycoplasma Hominis (MH) to 7 kinds of antimicrobial agents and comparison with that of UU infection in NGU patients, the in vitro susceptibility was determined by using microdilution method . The positive results were analyzed . The results showed that the sequence of susceptibility to 7 kinds of antimicrobial agents for both UU infection group and UU-MH mixed infection group was almost the same from the highest susceptibility to the lowest accordingly: Josamycin, Doxycycline, Minocycline, Sparfloxacin, Roxithromycin, Ofloxacin and Azithromycin . The total drug resistance rate for UU-MH mixed infection group (97.67%) was significantly higher than that for UU infection group (44.67%, P < 0.01) . The highest drug resistance rate in UU group and UU-MH mixed infection group was 31.33% (Ofloxacin) and 90.48% (Azithromycin) respectively . UU-MH mixed infection showed an increased drug resistance and changes of drug resistance spectrum. Rev Esp Quimioter, 2003 Jun, 16(2), 172 - 87 {MDR efflux pumps and antimicrobial resistance}; Sanchez Diaz P; The term MDR (Multi Drug Resistance) system refers to a group of transporters which are able to expulse a wide range of quite different substrates . While this type of system was first described in eukaryotic cells in the late 1980s, the presence of MDR efflux-pumps in bacteria showing resistance to several drugs has been increasingly reported in the literature . Under laboratory conditions the expression of these MDR systems is usually down-regulated . On occasion, basal expression of these efflux pumps is allowed in wild type strains, thus suggesting a role of these MDR systems in the intrinsic of these microorganisms resistance to antibiotics . On the other hand, overexpression of these MDR efflux pumps, after induction or because of the emergence of mutations in their regulatory elements, is also important in acquired resistance to antibiotics . This review summarizes the most relevant features of the MDR systems described in bacteria, as well as the mechanisms that regulate their expression. Drugs Today (Barc), 1999 Feb, 35(2), 89 - 103 Antibiotics in inflammatory bowel disease; Chung PY et al.; The use of antibiotics as primary therapy in inflammatory bowel disease (IBD) has been an issue of great controversy among the experts in the field . Although the utility of certain antimicrobial agents in managing secondary complications, such as abscess formation, toxic megacolon and pouchitis, has been substantiated by clinical trials, clear evidence to support or undermine their use as primary therapeutic agents in IBD is lacking . This may be secondary to the fact that the etiology of IBD remains unknown, and, despite much speculation and research in the area, no infectious agent has been found to cause or contribute to the pathogenesis of these disorders . The dearth of data, in turn, has resulted in widely varying treatment strategies and a lack of a clear standard of care with regard to the use of antibiotics . (c) 1999 Prous Science . All rights reserved. EMBO Rep, 2003 Oct, 4(10), 976 - 81 Epub 2003 Sep 12. Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses; Leulier F et al.; Human immunodeficiency virus 1 (HIV-1) expresses several accessory proteins that manipulate various host-cell processes to achieve optimum replicative efficiency . One of them, viral protein U (Vpu), has been shown to interfere with the cellular degradation machinery through interaction with SCF(beta-TrCP) complexes . To learn more about Vpu function in vivo, we used the genetically tractable fruit fly, Drosophila melanogaster . Our results show that the directed expression of Vpu, but not the non-phosphorylated form, Vpu2/6, in fat-body cells affects Drosophila antimicrobial responses . In flies, the Toll and Imd pathways regulate antimicrobial-peptide gene expression . We show that Vpu specifically affects Toll pathway activation by inhibiting Cactus degradation . Given the conservation of the Toll/nuclear factor-kappa B (NF-kappa B) signalling pathways between flies and mammals, our results suggest a function for Vpu in the inhibition of host NF-kappa B-mediated innate immune defences and provide a powerful genetic approach for studying Vpu inhibition of NF-kappa B signalling in vivo. J Antimicrob Chemother, 2003 Oct, 52(4), 555 - 63 Epub 2003 Sep 12. How good is the evidence for the recommended empirical antimicrobial treatment of patients hospitalized because of community-acquired pneumonia? A systematic review; Oosterheert JJ et al.; BACKGROUND: For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP) . A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e . Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected . However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP . We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone . METHODS: We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP . RESULTS: Eight relevant studies were selected . In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides . The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens . However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies . As a consequence, the results may have been influenced by confounding by indication . In addition, the outcomes showed several inconsistencies . CONCLUSIONS: A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies . Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data. Tuberculosis (Edinb), 2003, 83(5), 319 - 28 Role of Mycobacterium xenopi disease in patients with HIV infection at the time of highly active antiretroviral therapy (HAART) . Comparison with the pre-Haart period; Manfredi R et al.; BACKGROUND AND SETTING: A reliable and timely clinical, radiological, and bacteriological diagnosis, and an optimal treatment of non-tubercular mycobacteriosis (including Mycobacterium xenopi disease), remain an unanswered challenge for clinicians facing immunocompromised patients, including those with HIV infection . OBJECTIVE: The aim of our survey is to report the frequency, and the epidemiological, immunological, microbiological, clinical, and therapeutic features of all confirmed HIV-associated M . xenopi disease observed from 1993-2002, with special attention paid to eventual differences that emerged after the introduction of potent antiretroviral therapy (highly active antiretroviral therapy, HAART), on the basis of an international literature update . DESIGN AND RESULTS: Our series of 17 consecutive confirmed M . xenopi infections retrieved in 14 out of 3000 patients followed for HIV disease complications raises a broad series of clinical, diagnostic, therapeutic, and prophylactic concerns . The great majority of M . xenopi disease involved the lower respiratory tract, but atypical features including cavitation and prominent exudative features became apparent in patients successfully treated with HAART, pointing out the possible role of the so-called immune reconstitution syndrome in these episodes . CONCLUSIONS: Diagnostic problems represented by late or missed identification due to slow culture and frequently concomitant opportunistic disorders, join therapeutic difficulties due to the unpredictable in vitro antimicrobial susceptibility profile of these organisms, selection of treatment and chemoprophylaxis according with clinical-radiological and microbiological suspicion, and concomitantly administered medications. Southeast Asian J Trop Med Public Health, 2003 Mar, 34(1), 179 - 86 Utilization of restricted antibiotics in a university hospital in Thailand; Ayuthya SK et al.; Antibiotic resistance, a major negative consequence of antibiotic overuse, is an important problem worldwide . Various means have been used to control antibiotic usage including the use of an antibiotic order form (AOF), restricted antibiotic formularies and provision of educational information . The present study was designed to evaluate the use of antimicrobials in a 1,000-bed university hospital . Antimicrobial agents, likely to be abused namely ceftazidime, cefepime, cefoperazone/sulbactam, imipenem/cilastatin, meropenem, ciprofloxacin, netilmicin, vancomycin, azithromycin and clarithromycin, were selected for evaluation . A simple AOF with educational information was used as a mean to follow up the treatment . The investigator collected data from the filled AOF and the patient's charts of the Department of Internal Medicine from June to November 2000; all relevant data were assessed . The appropriateness of antibiotic use, assessed according to the criteria specified in the AOF, showed that 74% of these antibiotics were prescribed appropriately; this may prove the effectiveness of the system used in the present study . However, 348 of the 430 prescriptions (80.9%) were prescribed empirically at the initial stage for treatment of nosocomial infections in patients with serious conditions like pneumonia, sepsis and febrile neutropenia . Drugs that were frequently used empirically were ceftazidime (37.9%), imipenem/cilastatin or meropenem (19.3%), and cefoperazone/sulbactam (12.1%) respectively . Ceftazidime and imipenem/cilastatin or meropenem were also frequently used inappropriately among 111 prescriptions that were classified as an inappropriate prescribing . The most common misuses were prescriptions of the drug that did not follow the specified indications (70 prescriptions), no dosage adjustment in patients with renal impairment (39 prescriptions), improper dose (12 prescriptions) and improper dosing interval (9 prescriptions) . The results suggested overuse of certain antibiotics remain to be an unsolved problem . Better monitoring and strict controlled use of the problematic antibiotics, ie ceftazidime, imipenem/cilastatin or meropenem and vancomycin are essential to promote rational drug use as well as to reduce the frequency of drug resistance. N C Med J, 2003 Jul-Aug, 64(4), 148 - 56 Antibiotic prescriptions associated with outpatient visits for acute upper respiratory tract infections among adult Medicaid recipients in North Carolina; Brown DW et al.; BACKGROUND: North Carolina and the southeastern United States have the highest antimicrobial resistance rates for common respiratory tract pathogens in the nation . The excessive use of antibiotics for common outpatient infections is a major contributing factor in the emergence of antibiotic resistant bacteria . OBJECTIVE: To estimate the prevalence of oral antibiotic treatment for acute, nonbacterial respiratory tract infections among adult Medicaid recipients in North Carolina, and to describe a pilot project aimed at reducing the prevalence of oral antibiotic treatment among this population . METHODS: Using administrative claims data, we identified 24,137 Medicaid recipients, aged 18 to 64 years, who made at least one outpatient physician visit for acute nasopharyngitis (ICD-9, 460.x), acute pharyngitis (462.x), acute upper respiratory infection (465.9), acute bronchitis (466.0), or influenza (487.1) between October 1, 2000, and March 29, 2001 . We excluded adults with chronic bronchitis (ICD-9, 491.x), emphysema (492.x), asthma (493.x), or chronic obstructive pulmonary disease (496.x) . Pharmacy claims data were used to identify oral antibiotic treatment that occurred within 5 days of the outpatient visit . RESULTS: Overall, 63% (n = 15,189) of Medicaid recipients who made at least one outpatient visit during the observation period for one of the study conditions had a prescription filled for an oral antibiotic within 5 days . Residence in a rural county (64% vs . urban, 61%, p < 0.01) and in the eastern region of the state (65% vs . western region, 59%, p < 0.01) was associated with receipt of an antibiotic . Compared with the other principal study diagnoses, patients with acute bronchitis (44% of all outpatient visits) were 2.88 (95% CI = 2.72, 3.05) times more likely to receive oral antibiotic treatment after multivariate adjustment . SUMMARY: The prevalence of oral antibiotic treatment among adult Medicaid beneficiaries diagnosed with nonspecific upper respiratory infections, colds, pharyngitis, bronchitis, and influenza is high and varies significantly across patient demographics and geography . Interventions to reduce antibiotic prescribing are needed to reduce the progression of antimicrobial resistance. World Health Organ Tech Rep Ser, 2003, 918, i - vi, 1-59, back cover Evaluation of certain veterinary drug residues in food; Use of genetic profiling in leprosy to discriminate clinical forms of the disease; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USALeprosy presents as a clinical and immunological spectrum of disease . With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease . Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection . In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors . Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens. J Clin Endocrinol Metab, 2003 Sep, 88(9), 4426 - 31 Elafin in human endometrium: an antiprotease and antimicrobial molecule expressed during menstruation; King AE et al.; Elafin is an antiproteinase and antimicrobial molecule that is expressed at epithelial sites (for example, cervix) . This study details the expression and regulation of elafin in the human endometrium . Elafin mRNA and protein expression were examined in endometrium throughout the menstrual cycle and in first-trimester decidua . Real-time quantitative PCR showed that expression of elafin mRNA peaked during menstruation . Elafin protein was localized to leukocytes scattered in the endometrial stroma during the late secretory and menstrual phases . Faint immunostaining was also present in glandular epithelium at these cycle stages . Immunofluorescent colocalization of elafin with neutrophil elastase confirmed that elafin was expressed by endometrial neutrophils around the time of menstruation . This is consistent with the expression profile observed from immunohistochemical studies . Primary endometrial epithelial cells were treated with proinflammatory molecules, and elafin mRNA was studied . A combination of the proinflammatory mediators, IL-1 beta and TNFalpha, increased elafin mRNA levels by 4.6-fold . These results show that endometrium expresses elafin in a menstruation-dependent manner . This is attributable to the presence of infiltrating leukocytes and increased inflammatory signaling . Elafin will regulate proteolytic enzymes during menstruation and will contribute to the innate defense against uterine infection. Dev Comp Immunol, 2004 Feb, 28(2), 163 - 9 PR-39, a porcine antimicrobial peptide, inhibits apoptosis: involvement of caspase-3; Ramanathan B et al.; The porcine antimicrobial peptide, PR-39, has several activities beyond its function of killing bacteria . Here we report that PR-39 alters macrophage viability by inhibiting apoptosis, which was induced by nutrient depletion, LPS stimulation or camptothecin treatment . This antiapoptotic effect was pronounced resulting in significant reductions in annexin-V binding to externalized phosphatidylserine and was associated with a decrease in caspase-3 activity . These findings suggest that PR-39, a porcine neutrophil-derived antimicrobial peptide, might function in the inflammatory milieu not only to kill bacteria, but also to aid in modulating the viability of inflammatory cells by regulating apoptosis. Dev Comp Immunol, 2004 Feb, 28(2), 127 - 38 Isolation and characterisation of oncorhyncin II, a histone H1-derived antimicrobial peptide from skin secretions of rainbow trout, Oncorhynchus mykiss; Fernandes JM et al.; A potent antimicrobial peptide, tentatively named oncorhyncin II, was isolated from an acid extract of rainbow trout skin secretions . Amino acid sequencing showed that the first 17 residues of oncorhyncin II are identical to residues 138-154 of histone H1 from rainbow trout . Matrix-assisted laser desorption ionization mass spectrometry revealed that the purified peptide has a molecular mass of 7195.3Da . Taken together, these data indicate that oncorhyncin II is a 69-residue C-terminal fragment of histone H1, probably phosphorylated at two residues . Oncorhyncin II has minimal inhibitory concentrations in the submicromolar range against Gram-(+) as well as Gram-(-) bacteria and it does not display significant haemolytic activity towards trout erythrocytes . The purified peptide was found to induce a marked destabilisation of planar lipid bilayers without the formation of stable ion channels . Oncorhyncin II is possibly a cleavage product of histone H1 with a potentially important role in mucosal defence of rainbow trout. Dev Comp Immunol, 2004 Feb, 28(2), 89 - 95 Recognition of infectious non-self and activation of immune responses by peptidoglycan recognition protein (PGRP)-family members in Drosophila; Kurata S; Activation of the innate immune response involves recognition of the infectious non-self and subsequent activation of cellular and humoral reactions . Insect humoral reactions depend on primary and secondary responses . The primary response is mediated by the activation of cascades of constitutive proteins present in the hemolymph, such as the prophenoloxidase (proPO) cascade . The secondary response requires transcriptional activation of defense proteins, such as the induction of antimicrobial peptides . Drosophila possess specific mechanisms to discriminate between microbes and respond to infection by inducing the appropriate reactions . In innate immunity, pathogen-associated molecular patterns are recognized . The mechanisms for microbial recognition in Drosophila, however, are largely unknown . Recent data suggest that, in insect immunity, diverse peptidoglycan recognition protein members are involved in distinguishing between invading bacteria and activation of appropriate immune reactions. Parasite Immunol, 2003 May, 25(5), 259 - 70 Mucosal defences against Giardia; Eckmann L; Giardia lamblia (syn . G . duodenalis or G . intestinalis), the causative agent of giardiasis, is one of the most common causes worldwide of intestinal infections in humans . Symptomatic infection is characterized by diarrhoea, epigastric pain, nausea, vomiting, and weight loss, yet many infections are asymptomatic . The protozoan, unicellular parasite resides in the lumen and attaches to the epithelium and overlying mucus layers but does not invade the mucosa and causes little or no mucosal inflammation . Giardiasis is normally transient, indicating the existence of effective host defences, although re-infections can occur, which may be related to differences in infecting parasites and/or incomplete immune protection . Mucosal defences against Giardia must act in the small intestinal lumen in the absence of induction by classical inflammatory mediators . Secretory IgA antibodies have a central role in anti-giardial defence . B cell-independent mechanisms also exist and can contribute to eradication of the parasite, although their identity and physiological importance are poorly understood currently . Possible candidates are nitric oxide, antimicrobial peptides such as Paneth cell alpha-defensins, and lactoferrin . Elucidation of the key anti-giardial effector mechanisms will be important for selecting the best adjuvants in the rational development of vaccination strategies against Giardia. J Appl Microbiol, 2003, 95(4), 814 - 23 Patterns of antimicrobial activities from soil actinomycetes isolated under different conditions of pH and salinity; Basilio A et al.; AIMS: To evaluate the patterns of the production of antimicrobial compounds by diverse collection of actinomycetes isolated from different geographies under alternative conditions of pH and salinity in the media . METHODS AND RESULTS: Actinomycetes were grouped based on their method of isolation and their phenotype diversity was determined by total fatty acid analysis . A total of 335 representative isolates, including 235 Streptomyces species and 100 actinomycetes from other taxa, were screened for the production of antimicrobial activities against a panel of bacteria, filamentous fungi and yeasts, including some of clinical relevance . Production of antimicrobial activities was detected in 230 strains . In the case of the genus Streptomyces, 181 antimicrobial activities (77% of the tested isolates) were recorded . The activities observed among the other actinomycetes taxa were lower (49% of the tested isolates) . CONCLUSIONS: The results of this study support the idea that species of actinomycetes isolated in alternative selective conditions of pH and salinity present a significant capacity to produce compounds with antibacterial or antifungal activity . The best group of isolates in terms of production of active secondary metabolites was the one isolated in saline conditions . SIGNIFICANCE AND IMPACT OF THE STUDY: The results demonstrate that these actinomycetes strains isolated in alternative selective conditions of pH and salinity and collected from diverse geographical locations present a significant capacity to produce compounds with antibacterial or antifungal activity. J Appl Microbiol, 2003, 95(4), 734 - 43 A model for the efficacy of combined inhibitors; Lambert RJ et al.; AIMS: The method of the sum of the fractional inhibitory concentrations (SigmaFIC) is used ubiquitously in the investigation of antimicrobial combinations . The inherent assumption of this simple equation is that in a mixture all antimicrobials have identical dose responses . The aim of this work was to analyse the outcome of removing this assumption . METHODS AND RESULTS: A model to describe the efficacy of combined inhibitors was produced which removed the assumption of identical dose responses . The results of several checkerboard experiments showed that the new model, termed the facomb was a more general form of the SigmaFIC method, but the features described by the SigmaFIC as either synergy or antagonism could be attributed to differences in the dose responses of antimicrobials in combination . Where the model failed to adequately describe experimental data it was suggested that these might be cases of true antagonism or synergy . CONCLUSIONS: The SigmaFIC methodology used to describe the effect of antimicrobial combinations (preservatives and antibiotics) is valid only when it is demonstrated that individual components of the mixture have identical dose responses . Otherwise the SigmaFIC method is invalid . Descriptions of antimicrobial synergy may simply be due to the mixing of antimicrobials with differing dose responses . SIGNIFICANCE AND IMPACT OF THE STUDY: Studies aimed at producing synergistic mixtures of antimicrobials, which ignore the dose response of the individual antimicrobials, may waste valuable research effort looking for a physiological explanation for an apparent synergy, where none, in-fact, exists . Conversely, mixing antimicrobials with very different dose responses might lead to mixtures with an 'apparent' synergy which may themselves be very useful therapeutically. Biotechnol Bioeng, 2003 Nov 5, 84(3), 374 - 81 Inducible expression of green fluorescent protein in porcine tracheal epithelial cells by the bovine tracheal antimicrobial peptide promoter; Dyce PW et al.; Tracheal antimicrobial peptides (TAP) are expressed primarily in respiratory epithelial cells of cattle . The TAP expression is inducible upon challenge with bacteria and bacterial lipopolysaccharide (LPS) . In pigs, a promoter that can be activated by bacterial infection has yet to be identified . The objective of this study was to use green fluorescent protein (GFP) as a reporter gene to determine the function and inducibility of the bovine TAP promoter in porcine primary tracheal epithelial cells . Thus, evaluating the feasibility of using this promoter to direct transgene expression in porcine cells.The percentage of GFP expressing cells increased in response to LPS challenge in both a dose-dependent and time-dependent manner (p < 0.05) . Moreover, when the intensity of the GFP fluorescence was measured, it was observed that the percentage of cells that have a high intensity of GFP fluorescence, also increased gradually as LPS dose increased, the difference between the unchallenged (control) and challenged group become statistically significant at the concentration of 100 ng/mL after 36 h LPS challenge (p < 0.05) . The level of induced-expression driven by the TAP promoter was 67.8 +/-12.2% that of the cytomegalovirus (CMV) promoter . The intensity of GFP fluorescence by the TAP promoter was 39.8 +/- 7.6% when compared to the expression driven by the CMV promoter . These data suggest the TAP promoter functions at a lower, but comparable, level to the strong CMV promoter.Our data demonstrated that the bovine TAP promoter was functional in porcine primary tracheal epithelial cells . The ability of the TAP promoter to control gene expression in an inducible manner in the porcine respiratory tract presents an important application potential in transgenic animal studies . Arch Pharm Res, 2003 Aug, 26(8), 597 - 600 Gram-positive bacteria specific properties of silybin derived from Silybum marianum; Lee DG et al.; Silybin has a potent antibacterial activity, more potent than silymarin II, against gram-positive bacteria without hemolytic activity, whereas it has no antimicrobial activity against gram-negative bacteria or fungi . The mode of action of silybin against the gram-positive bacterial cell was examined by investigating the change in plasma membrane dynamics of bacterial cells using 1,6-diphenyl-1,3,5-hextriene (DPH) as a membrane probe and by assessing the inhibition of macromolecular synthesis using radiolabeled incorporation assay . The results showed that silybin inhibited RNA and protein synthesis on gram-positive bacteria. Pharmazie, 2003 Aug, 58(8), 587 - 9 Constituents of Peucedanum zenkeri seeds and their antimicrobial effects; Ngwendson JN et al.; The methanol extract of Peucedanum zenkeri L . seeds showed antimicrobial activity which is concentrated in the n-hexane fraction . Bioactivity-guided chromatographic fractionation of the seeds of P . zenkeri led to the isolation and characterization of five major coumarins, umbelliprenin, imperatorin, bergapten, isopimpinellin and byakangelicin, as well as two minor coumarins, 7-methoxy coumarin and 5-hydroxy-8-methoxy psoralen . Amongst the isolated compounds only imperatorin, bergapten and isopimpinellin were found to possess anti-microbial activity. J Prosthodont, 2003 Jun, 12(2), 73 - 81 Postcementation hypersensitivity: scientific data versus dentists' perceptions; Rosenstiel SF et al.; PURPOSE: The purpose of this article was to obtain dentists' opinions via an Internet survey as to the prevalence, causes, and prevention of postcementation sensitivity and compare their responses with published data on the problem . MATERIALS AND METHODS: Information as to respondents opinions of postcementation sensitivity was obtained from an Internet survey asking about their experience and for a ranking of the importance of each of 15 factors . RESULTS: A total of 466 valid responses were received . The incidence of postcementation sensitivity was estimated to be less than 2% by more than 2/3 of the dentists . The factors considered "very important" in reducing sensitivity by more than 50% of the respondents were desiccation, luting agent, occlusion, provisional, and water spray . CONCLUSIONS: Comparing respondents' opinions with published clinical studies, the incidence of postcementation sensitivity appears to be underestimated . There is little published evidence to support the importance of antimicrobials, desensitizing, or bonding agents, although these are considered effective by some dentists . Many respondents consider luting agent to be an important variable. Braz Dent J, 2003, 14(2), 75 - 81 Epub 2003 Oct 03. Effect of caries preventive measures directed to expectant mothers on caries experience in their children; Zanata RL et al.; The aim of this prospective study was to determine the effectiveness of caries preventive measures started during pregnancy on the caries experience of first-time mothers and their infants . Eighty-one pregnant women with low social background were selected on the basis of the presence of active carious lesions and were randomly divided into control (38) and experimental (43) groups . The initial dental status (DMFS and white spot lesions) was established through clinical examination . The prophylactic measures were repeated during pregnancy and 6 and 12 months after delivery . Both groups received primary care intervention . They were instructed in relation to the etiologic factors of dental caries and received oral hygiene kits . Oral hygiene instructions were reinforced through interactive brushing . The experimental group also received antimicrobial treatment (topical application of NaF and iodine solution immediately after prophylaxis and 3 and 5 days later) and restorative care using glass ionomer cement . By the time the children were 2 years of age, 33.3% of the infants in the control group and 14.7% in the experimental group had caries activity . A significant difference in caries prevalence was observed between children with and without visible dental plaque . The mean number of tooth surfaces with carious lesions (including areas of demineralization) was higher among the children in the control group compared to the experimental group (6.3 x 3.2), however, with no statistical significance . Maternal caries increase was a significant factor influencing the caries experience of the children . These data support the evidence of an association between caries prevalence in young children and clinical (dental plaque) and maternal factors. Br J Clin Pharmacol, 1993 Dec, 36(6), 511 - 9 A survey of undergraduate and continuing medical education about antimicrobial chemotherapy in the United Kingdom . British Society of Antimicrobial Chemotherapy Working Party on Antimicrobial Use; Davey P et al.; 1 A questionnaire about undergraduate teaching on antimicrobial chemotherapy was sent to academic Departments of Clinical Pharmacology, Pharmacology and Medical Microbiology throughout the UK . 2 Questionnaires about postgraduate lectures and information circulated to doctors about antimicrobial chemotherapy were sent to Drug Information Centres and Postgraduate Tutors throughout the UK . Review articles and editorials in general medical journals were assessed . 3 The median amount of core undergraduate teaching on antimicrobial chemotherapy was 13.5 h but the range was from 9.0 h to 102.0 h . Content was predominantly oriented towards drugs rather than diseases and towards prescribing in hospital rather than in the community . Most teaching was by formal lecture as part of a core programme . On a scale from 0 to 5 the median emphasis given to individual topics ranged from 2.50 to 3.75 but the range of emphasis given by individual medical schools was wide, for example from 1.00 to 4.50 for teaching on pharmacokinetics . 4 Postgraduate tutors identified advice from local specialists and requests from local practitioners as the most important determinants of content of continuing medical education . Material from drug information centres was predominantly oriented towards discussion of individual drugs rather than management of specific diseases and even this limited survey found evidence of duplication . The UK general medical literature contained a total of 112 reviews or editorials on antimicrobial chemotherapy covering a wide range of topics but these were not, and should not be assumed to be comprehensive . 5 Almost all doctors regularly prescribe antimicrobials and require education about the subject . Wide variations in current medical practice should be addressed explicitly through more extensive use of problem solving . The literature suggests that knowledge is most effectively disseminated through local networks of practitioners . There should be more national co-ordination of the content of information to be disseminated through the existing drug information networks. J Am Acad Dermatol, 2003 Sep, 49(3 Suppl), S227 - 32 Cumulative irritancy comparison of adapalene gel 0.1% versus other retinoid products when applied in combination with topical antimicrobial agents; Brand B et al.; This randomized, investigator-blinded study evaluated the level of skin tolerance to adapalene gel 0.1%, tretinoin cream 0.025%, or tretinoin microsphere gel 0.1% when applied in combination with clindamycin phosphate lotion 1%, erythromycin gel 2%, benzoyl peroxide gel 5%, or erythromycin-benzoyl peroxide gel . A total of 37 subjects underwent daily application of the topical antimicrobial and retinoid products to sites on their upper back under protective patches for approximately 16 hours each day; Friday patches were left in place over the weekend . Testing continued daily for 3 weeks or until discontinuation caused by a severe adverse reaction to any of the test products or to the patch . Adapalene gel 0.1% demonstrated statistically significantly (P <.001) less irritation after repeated application under occlusive conditions than tretinoin cream 0.025% or tretinoin microsphere gel 0.1% . Moreover, the application of adapalene gel 0.1% under these conditions, concomitantly with various antimicrobial agents, was safe and well tolerated in this subject population . In view of its low irritation potential and its efficacy, adapalene gel 0.1%, in combination with antimicrobial agents should be considered for the treatment of acne vulgaris. J Am Acad Dermatol, 2003 Sep, 49(3 Suppl), S200 - 10 A review of the use of combination therapies for the treatment of acne vulgaris; Leyden JJ; Acne is a disease of the pilosebaceous unit, involving abnormalities in sebum production, follicular epithelial desquamation, bacterial proliferation, and inflammation . The major classes of therapeutic agents are topical and systemic retinoids, antimicrobial agents, and systemic hormonal drugs . Combination therapy with a topical retinoid and an antibiotic can normalize follicular epithelial desquamation and reduce bacterial proliferation . The new retinoids (eg, adapalene) have an additional antiinflammatory action along with their effect on the preclinical microcomedo and, coadministered with a topical or an oral antibiotic, are a rational initial therapy for all but the most severe forms of acne . Retinoids can also be used alone for long-term maintenance to prevent the reemergence of comedones and inflammatory acne lesions and to spare the use of antibiotics, thus helping to reduce the risk of bacterial resistance. Biochem Biophys Res Commun, 2003 Sep 26, 309(3), 591 - 7 Solution structure of termite-derived antimicrobial peptide, spinigerin, as determined in SDS micelle by NMR spectroscopy; Lee KH et al.; Spinigerin is a linear antibacterial peptide derived from a termite insect . It consists of 25 amino acids and is devoid of cysteines . Spinigerin displays good lytic activities against Gram-positive and Gram-negative bacteria, but has no hemolytic activities against human erythrocytes . In this study, we present a three-dimensional solution structure of spinigerin in SDS micelles . According to CD data spinigerin has an alpha-helical conformation in the presence of TFE, DPC micelles, and SDS micelles . The three-dimensional structure of spinigerin as determined by NMR spectroscopy contains a stable alpha-helix from Lys4 to Thr23 . Spinigerin (4-21), an 18-residue fragment from Lys4 to Leu21, contains a similar content of alpha-helical structure compared to native spinigerin and was found to retain antibacterial activity, too . Therefore, this alpha-helical structure and the strong electrostatic attraction between four Lys and three Arg residues in spinigerin and the negatively charged polar head groups of the phospholipids on the membrane surface play important roles in disrupting membrane and subsequent cell death. Transplant Proc, 2003 Aug, 35(5), 2006 - 8 Pulmonary nocardiosis in heart transplant recipients: treatment and outcome; Peraira JR et al.; BACKGROUND: Nocardial infections typically affect patients receiving immunosuppressants, occurring early after surgery in 3% to 40% of heart transplant (HTx) recipients . The emergence of antibiotic resistance and occurrence of disease recurrences in AIDS population has engendered controversy about the treatment for immunodepressed HTx patients . METHODS: We present a retrospective study of the diagnosis, treatment and outcome of 560 HTx recipients between 1984 and 2002 . RESULTS: Among the five cases of Nocardia infection (0.9%), three cases developed late after HTx (between 3.1 and 11 years follow-up) . All patients had pulmonary disease and one in addition had subcutaneous nodules . Microbiological diagnosis required open lung biopsy in one case . All patients were treated primarily with trimethoprim-sulphamethoxazole, but evidence of resistance to sulfonamides led us to change the antimicrobial combination in two cases . Four patients who received one year of antibiogram-guided therapy showed complete healing without recidivism . Three patients died, all due to non-related causes, at follow-ups between 1 and 5 years . In one case a cutaneous recurrence of disease was attributed to noncompliance . CONCLUSIONS: Nocardiosis in current HTx is less common than previously reported . Its incidence seems to be delayed in time with modern immunosuppressants . Given the high incidence of sulfamide resistance, treatment must be guided by antibiotic sensitivity . We believe that maintenance therapy for a whole year is the appropriate option in order to avoid recidivism in this population. Transplant Proc, 2003 Aug, 35(5), 1999 - 2000 High incidence of severe infections in heart transplant recipients receiving tacrolimus; Peraira JR et al.; BACKGROUND: Tacrolimus (FK) is being increasingly used as an alternative to cyclosporine (CyA) in heart transplantation (HTx) . It is believed to engender slightly more powerful protection against acute rejection . However, the increased immunosuppression could result in an excess of infectious complications . METHODS: Our study compared the incidence of major infections (MInf), defined as life-threatening infectious episodes requiring admission and intravenous (IV) antimicrobial therapy, among a series of HTx recipients treated with either FK (n=30) or CyA (n=84) . RESULTS: A total of 21 patients received FK in an elective protocol and 9 patients initially treated with CyA were converted to FK . Tacrolimus was combined with azathioprine and prednisone in 21 cases, and with mycophenolate mofetil and steroids in 8 recipients . After a follow-up between 6 and 37 months, 11 patients (37%) in the FK group developed 13 episodes of MInf, most (85%) occurring during the first posttransplant year . Conversely, CyA patients (n=84), a group with similar characteristics and follow-up, showed a MInf incidence of 12% (P<.05) . Among the FK group, the most common site of MInf was pulmonary (69%) . A variety of opportunistic agents caused MInf in 54% of cases, whereas the remaining ones were attributed to nosocomial bacteria . There were three deaths (27% of all MInf), all in azathioprine-treated patients with initial FK therapy . CONCLUSIONS: Tacrolimus therapy seems to be associated with an increased incidence of severe infections in HTx recipients . We recommend aggressive diagnostic and therapeutic approaches for patients on FK who develop signs or symptoms of infection in the first year after HTx. J Chemother, 2003 Aug, 15(4), 342 - 9 Post-exposure effects of cefepime and cefpirome on isogenic Escherichia coli hosts producing SHV-extended-spectrum beta-lactamases; Bedenic B et al.; Persistent suppression of bacterial growth after short antimicrobial exposure is called postantibiotic effect (PAE) . By definition, there should be no subinhibitory concentrations of antimicrobial agent left when the postantibiotic effect starts . However, if subinhibitory concentrations are maintained after removing the antibiotic, the recovery period of the treated cultures is markedly prolonged . This is defined as postantibiotic-sub-MIC-effect (PA-SME) . The aim of this study was to determine the PAE and PA-SME of cefpirome and cefepime on isogenic Escherichia coli strains producing SHV-2, SHV-5, and SHV-12 extended spectrum beta-lactamases (ESBL) compared to a non-ESBL E . coli strain . It was hypothesized that the presence of an ESBL would hydrolyze the cephalosporin molecule before it exerted a toxic effect on the bacterial cell and thus shorten the duration of PA-SME . Cefpirome and cefepime had no PAE against ESBL producing E . coli or it was of a short duration and present only at high antibiotic concentrations, but exposure to subinhibitory concentration of those antibiotics in the PA (postantibiotic) phase resulted in a significant delay of regrowth . The effect was more pronounced with higher concentrations of antibiotics, and uninfluenced by the type of enzyme and the antibiotic . The present study shows that the presence of subinhibitory concentrations of cefepime and cefpirome in the medium after exposure to suprainhibitory concentrations results in a significant delay of regrowth of both ESBL-positive and negative E . coli strains . The production of SHV-2, SHV-5 and SHV-12 ESBLs did not shorten the duration of the PA-SME. J Immunol, 2003 Sep 15, 171(6), 3262 - 9 Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes; Nomura I et al.; Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases . However patients with AD, but not psoriasis, suffer from frequent skin infections . To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays . The expression of innate immune response genes, human beta defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016) . Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005) . By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-alpha, IFN-gamma, and IL-1beta . Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro . We found that IL-13 and IL-4 inhibited TNF-alpha- and IFN-gamma-induced HBD-3 production . These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-alpha and IFN-gamma under inflammatory conditions in AD skin . These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases. J Leukoc Biol, 2004 Jan, 75(1), 39 - 48 Epub 2003 Jul 22. Cathelicidins, multifunctional peptides of the innate immunity; Zanetti M; Cathelicidins comprise a family of mammalian proteins containing a C-terminal cationic antimicrobial domain that becomes active after being freed from the N-terminal cathelin portion of the holoprotein . Many other members of this family have been identified since the first cathelicidin sequences were reported 10 years ago . The mature peptides generally show a wide spectrum of antimicrobial activity and, more recently, some of them have also been found to exert other biological activities . The human cathelicidin peptide LL-37 is chemotactic for neutrophils, monocytes, mast cells, and T cells; induces degranulation of mast cells; alters transcriptional responses in macrophages; stimulates wound vascularization and re-epithelialization of healing skin . The porcine PR-39 has also been involved in a variety of processes, including promotion of wound repair, induction of angiogenesis, neutrophils chemotaxis, and inhibition of the phagocyte NADPH oxidase activity, whereas the bovine BMAP-28 induces apoptosis in transformed cell lines and activated lymphocytes and may thus help with clearance of unwanted cells at inflammation sites . These multiple actions provide evidence for active participation of cathelicidin peptides in the regulation of the antimicrobial host defenses. J Leukoc Biol, 2004 Jan, 75(1), 34 - 8 Epub 2003 Jul 15. Antimicrobial polypeptides; Ganz T; The respiratory tract presents a large and potentially vulnerable surface to inhaled microbes . It is coated by a thin layer of secretions generated by airway epithelial cells, submucosal glands, resident and recruited phagocytes (neutrophils, eosinophils, monocytes, and macrophages) and alveolar epithelial cells, as well as substances that enter from blood plasma . More than 80 years ago, Alexander Fleming observed that respiratory secretions have microbicidal and microbistatic properties . He described the activity of lysozyme, one of the principal polypeptides of these secretions . Since then, a number of additional antimicrobial components have been identified, and there is increasing insight into their complex interactions . This review is an update of my previous summary of this area. J Leukoc Biol, 2003 Oct, 74(4), 542 - 50 Epub 2003 Jul 01. Targeting myeloperoxidase to azurophilic granules in HL-60 cells; Lemansky P et al.; Myeloperoxidase (MPO) is a cationic protein and one of the major constituents of azurophilic granules in neutrophils . Here, we examined whether intracellular transport of MPO and serglycin, a chondroitin sulfate (CS)-bearing proteoglycan, is correlated . First, we examined binding of MPO to CS-Sepharose and measured an ionic interaction, which was disrupted by 200-400 mM NaCl . Next, HL-60 promyelocytes were activated with a phorbol ester, which induced an almost complete rerouting of serglycin from the granular to the secretory pathway, concomitant with a similar effect on MPO transport and secretion . We then used the membrane-permeable cross-linker dithiobis(succininmidylpropionate; DSP) after labeling HL-60 cells with {35S}methionine and {35S}cysteine for 19 h . Immunoprecipitation of MPO revealed its cross-linking to high molecular material having the appearance of a proteoglycan in sodium dodecyl sulfate-polyacrylamide gels . This assumption was confirmed by labeling HL-60 cells with {35S}sulfate for 10 min followed by DSP cross-linking and immunoprecipitation . From three granular enzymes immunoprecipitated, only the cationic MPO was cross-linked to {35S}sulfate-labeled serglycin in appreciable quantities, whereas cathepsin D or beta-N-acetylhexosaminidase was not . Thus, intracellular transport of MPO appears to be linked to that of serglycin . Extracts from high buoyant density organelles from human placenta containing MPO activity were subjected to CS-affinity chromatography . Proteins binding to CS were identified by mass spectrometry as MPO, lactoferrin, cathepsin G, and azurocidin/cationic antimicrobial protein of molecular weight 37 kDa, suggesting that serglycin may be a general transport vehicle for the cationic granular proteins of neutrophils. Biomacromolecules, 2003 Sep-Oct, 4(5), 1264 - 8 Nonnatural branched polysaccharides: synthesis and properties of chitin and chitosan having disaccharide maltose branches; Kurita K et al.; Synthesis and properties of chitin and chitosan derivatives having beta-maltoside branches at C-6 have been studied . Chitosan was first transformed into an organosoluble acceptor having a reactive group only at C-6, 3-O-acetyl-2-N-phthaloyl-6-O-trimethylsilylchitosan . Glycosylation with an ortho ester from d-maltose was performed successfully at room temperature in dichloromethane in the presence of trimethylsilyl trifluoromethanesulfonate as the catalyst . The degree of substitution could be controlled by the reaction conditions and was up to 0.56 . Full deprotection gave chitosan with maltoside branches, and the subsequent N-acetylation resulted in the formation of the corresponding chitin derivative . The introduced disaccharide unit improved hydrophilic properties considerably compared to monosaccharide units as confirmed by high solubility in water and moisture absorption and retention ability . The enzymatic degradability and antimicrobial activity were moderate probably because of the bulky nature of the branches. J Comb Chem, 2003 Sep-Oct, 5(5), 597 - 605 A positional scanning combinatorial library of peptoids as a source of biological active molecules: identification of antimicrobials; Humet M et al.; A positional scanning library of N-alkylglycine trimers (peptoids) containing over 10 000 compounds has been synthesized on solid phase . The synthetic pathway involved the use of the submonomer strategy and a set of 22 commercially available primary amines as a chemical diversity source . The unbiased nature of the library allowed its screening against a variety of biological targets, leading to the identification of individual peptoids exhibiting remarkable biological activities (Garcia-Martinez, C . et al . Proc . Natl . Acad . Sci . U.S.A . 2002, 99, 2374 . Montoliu, et al . J . Pharm . Exp . Therap . 2002, 302, 29 . Planells-Cases, R., et al . J . Pharm . Exp . Therap . 2002, 302, 163) . In the present work, the screening of this library against a panel of Gram-positive and Gram-negative bacteria led to the identification of different compounds exhibiting antimicrobial activity. J Am Vet Med Assoc, 2003 Sep 1, 223(5), 677 - 83 Health performance of feeder calves sold at conventional auctions versus special auctions of vaccinated or conditioned calves in Ontario; Macartney JE et al.; OBJECTIVE: To compare health performance during the first 28 days in the feedlot for vaccinated or conditioned feeder calves sold through special auctions in Ontario with health performance for calves sold through conventional auctions in the province . DESIGN: Cohort study . ANIMALS: 12,313 calves sold through conventional and special auctions at the Keady Livestock Market during the fall of 1999 and 2000 . PROCEDURE: Buyers of calf groups were approached at the auction market or contacted by telephone and asked to record the number of calves requiring treatment for bovine respiratory tract disease (BRD) during the first 28 days after purchase . RESULTS: 211 calf groups (> or = 20 calves/group) were followed up for 28 days after purchase . Multivariate logistic analysis indicated that vaccinated calves purchased through special auctions were 0.68 (95% confidence interval, 0.50 to 0.93) times as likely to receive treatment for BRD as were calves purchased at conventional auctions and that conditioned calves were 0.22 (95% confidence interval, 0.12 to 0.38) times as likely to receive treatment . Groups that received antimicrobials by injection on arrival at the feedlot were 0.64 (95% confidence interval, 0.43 to 0.96) times as likely to be treated as were groups that did not . CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that vaccinated and conditioned calves were less likely to receive treatment for BRD during the first 28 days in the feedlot; however, there was no difference in mortality rate. Front Biosci, 2003 Sep 01, 8, s769 - 82 Lyme disease and the heart; Haddad FA et al.; Lyme carditis is typically characterized by varying degrees of intermittent atrioventricular block occurring within weeks of infection with Borrelia burgdorferi . Myocarditis and/or pericarditis may occur . Cardiomyopathy has been associated with B . burgdorferi in Europe, but not in the United States . Patients with unexplained atrioventricular block or myopericarditis should be questioned for recent travel to tick-endemic areas, and for a history of erythema migrans rash, "viral-like" illness, aseptic meningitis, cranial nerve palsy, radiculitis, or oligoarthritis . However, the absence of a recognized tick bite or rash does not rule out Lyme disease . The diagnosis of Lyme carditis should be supported by the presence of concurrent erythema migrans, or by positive results of 2-step laboratory testing for antibodies to B . burgdorferi . False positive results may occur, emphasizing the importance of clinical judgment in attributing specific manifestations to B . burgdorferi infection . Carditis generally resolves spontaneously, but antimicrobial therapy can shorten symptom duration and prevent potential cardiac and non-cardiac sequelae . Cardiac manifestations generally resolve spontaneously, but antimicrobial therapy can shorten symptom duration and prevent potential cardiac and non-cardiac sequelae . The prognosis for Lyme carditis is excellent. Front Biosci, 2003 Sep 01, 8, s862 - 73 Mechanism of antibiotic efflux in Gram-negative bacteria; Zgurskaya HI et al.; Active efflux of antibiotics mediated by multidrug transporters is a mechanistic basis of multidrug resistance in bacteria . The most versatile multidrug transporters are those found in Gram-negative bacteria . They have a high level of constitutive expression and provide an immediate response to structurally diverse antimicrobial agents including clinically important antibiotics . The versatility and efficiency of multidrug transporters in Gram-negative bacteria heavily depend on coupling of drug efflux with the transport across the outer membrane . The coupling is achieved through the assembly of multi-component protein complexes that span both the inner and the outer membranes of Gram-negative bacteria . In this review we discuss the mechanistic and structural features of multidrug efflux complexes with the major focus on the tight coupling of drug efflux with transport across the outer membrane. Int J Dermatol, 2003 Sep, 42(9), 707 - 8 Relapsing polychondritis; Liu CM et al.; A 43-year-old Chilean man presented with a 5-month history of progressive hypertrophy of the ears bilaterally . He was seen initially by a dermatologist in Chile for complaints of erythema and swelling of the ears, and had been treated unsuccessfully with topical steroids and antimicrobial ointments . On presentation to our clinic, the hypertrophy had stabilized and the erythema had resolved, but he complained of decreased hearing due to narrowing of the external auditory canal . Associated symptoms included occasional pruritus, but he denied any pain . He also denied a history of sinus problems, respiratory symptoms, ocular pain, chest pain, and arthralgias . Physical examination revealed firm hypertrophy of the collagenous areas of both ears, sparing the ear lobes (Fig . 1) . No pain was elicited on palpation . No conjunctivitis was noted and the nasal passages were clear . His chest was clear to auscultation . Histologic examination revealed a minimal perivascular infiltrate of lymphocytes and plasma cells in the dermis with fibrosis of the subcutis (Fig . 2) . Blood tests showed a normal complete blood count, antinuclear antibody, and rheumatoid factor . Anti-collagen II antibodies were elevated at 29.2 Eu/ml (normal, 0-20 Eu/ml; borderline, 20-25 Eu/ml; elevated, > 25 Eu/ml). Schweiz Monatsschr Zahnmed, 2003, 113(7), 756 - 63 {Irrigants and intracanal medicaments in endodontics}; Zehnder M et al.; Modern, biologic root canal therapy should be performed with suitable irrigating solutions and intracanal medicaments . The goal of endodontic treatment is to free the treated tooth from infection and prevent reinfection as thoroughly as possible by means which do not put the organism at risk . In this review of the literature, an evidence-based concept for irrigation and medication of root canal systems is presented . Irrigants and medicaments are discussed with respect to their antimicrobial, tissue-dissolving and endotoxin-decontaminating capacity in relation to their systemic toxicity . Recent findings pertaining to interactions of root canal medicaments and irrigating solutions and their impact on a sound irrigating and medicating concept are discussed. J Palliat Care, 2003 Summer, 19(2), 95 - 9 Evaluation of a nystatin-containing mouth rinse for terminally ill patients in palliative care; Butticaz G et al.; PURPOSE: To evaluate the antifungal effect of a nystatin mouth rinse to control oral candidiasis of elderly patients in palliative care . MATERIALS AND METHODS: 52 cancer patients (mean age: 83 years) hospitalized in a long term care facility for chronically ill geriatric patients . Mouth rinsing with 15 ml nystatin solution (4,000 Ul/ml) was carried out for one minute, six times daily, over two weeks . Yeasts were collected and seeded on CHROMagar . Growth was read qualitatively and quantitatively after two days' incubation at 37 degrees C . RESULTS: Clinical signs of oral candidiasis were observed in 31% of cases . High yeast scores were observed in 58% of the residents . There was an association between signs of oral candidiasis and high yeast scores (p < 0.001) . Treatment for two weeks caused no clinical changes nor reduced yeast scores . CONCLUSIONS: No clinical or antifungal effect from the nystatin suspension suggests that the concentration of nystatin in the mouth rinse was too low . A more effective procedure should be employed for antifungal treatment of terminally ill patients . Appropriate antimicrobial solutions with lubricating activity should be developed and applied to prevent oral diseases. Clin Infect Dis, 2003 Sep 15, 37(6), 853 - 6 Epub 2003 Aug 27. Do resident physicians use antibiotics appropriately in treating upper respiratory infections? A survey of 11 programs; Fakih MG et al.; We surveyed resident physicians of 11 primary care programs regarding the management of upper respiratory infections and antibiotic resistance . Although they viewed excess antibiotic use as the most important factor increasing resistance, they had little knowledge regarding antimicrobial resistance and were willing to prescribe antibiotics for common viral illnesses. J Med Chem, 2003 Sep 11, 46(19), 4173 - 81 Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds; Thorsteinsson T et al.; A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized . These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group . They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks . However, their chemical stability has to be adequate in order for them to have antimicrobial effects . Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability . Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log . The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C. Microbiol Immunol, 2003, 47(7), 527 - 31 Prevalence of inherited myeloperoxidase deficiency in Japan; Nunoi H et al.; The microbicidal activity of the myeloperoxidase (MPO)-hydrogen peroxide-halide system has been implicated as the most efficient, oxygen-dependent antimicrobial component of neutrophil host defense . Unexpectedly, individuals with MPO deficiency suffer few clinical consequences . In order to understand better the clinical impact of MPO deficiency, we surveyed several clinical hematology laboratories in Japan to assess the prevalence of MPO deficiency in the general population . MPO activity was determined by flow cytometry using the Technicon H series of automated systems . We identified 26 cases of complete MPO deficiency, prevalence 1 in 57,135, and 129 cases of partial deficiency, prevalence 1 in 17,501 . The distribution of complete and partial deficiencies differed among the laboratories studied. Ned Tijdschr Tandheelkd, 2003 Aug, 110(8), 321 - 7 {110th volume of Dutch Journal of Dentistry 3 . Developments in the treatment of oral and craniomaxillofacial trauma during the last five decades}; Stoelinga PJ; A historical review is presented on the development of the treatment of trauma of the maxillofacial skeleton in the context of international as well as national literature . The review has been divided in three periods: the period before the prophylactic use of antimicrobial agents (before 1950), the years of open reduction with wire osteosynthesis (1950-1980) and the period till present in which open reduction is combined with rigid internal fixation (after 1980) . The latter period is also marked by the application of the principles of primary bone healing, whereas access to the maxillofacial skeleton is gained through a coronal incision, where needed. Arch Pharm (Weinheim), 2003 Aug, 336(6-7), 336 - 44 Novel high energy intermediate analogues with a triazasterol structure as potential ergosterol biosynthesis inhibitors IV: antimicrobial activity of mono-, bi-, and tricyclic 8, 13, 15-triazasteroid analogues including the synthesis of novel 4-alkylamino- and 4-alkenylamino-9-hydroxypyrimidoisoquinolines; Gossnitzer E et al.; 4-alkylamino-and 4-alkenylamino-9-hydroxy-1, 6, 7, 11b-tetrahydro-2H-pyrimido{4, 3-a}isoquinolines were designed as inhibitory tricyclic triaza-analogues of carbocationic high energy intermediates (HEI) of enzymes involved in fungal ergosterol biosynthesis . Various routes for effective synthesis of 9-hydroxypyrimidoisoquinolines from 9-methoxythiones were investigated . The ether cleavage of 9-methoxy-pyrimidoisoquinolines, a key step in the synthesis, was carried out using various protocols . The structures of the obtained 9-hydroxy compounds were confirmed using homo- and hetero-nuclear correlated 1D and 2D NMR experiments . In vitro antifungal susceptibility tests of the alkylaminohydroxypyrimidoisoquinolines revealed weak to good antimycotic effects . The maximum antifungal efficacy was found for 4-{(3R)-6-isopropyl-3-methyl-6-heptenylamino}-9-hydroxypyrimidoisoquinoline . Furthermore, the in vitro activities of the newly synthesized 9-hydroxypyrimidoisoquinolines and of a series of prepared 8, 13, 15-triazasteroid analogues (N-alkyl-N'-(phenethyl- and cyclohexenylethyl)guanidines, N(2) -and N(2), 4-substituted imidazolin-2-amines, and N(4)-alkylaminopyrimidoisoquinolines) against representatives of gram-positive and gram-negative bacteria were investigated . The compounds showed significant antibacterial effects against gram-positive bacteria. Biosci Biotechnol Biochem, 2003 Aug, 67(8), 1844 - 6 Paradoxical effect of synthetic hydroxy isothiocyanates on antimicrobial action of aminoglycosides; Tajima H et al.; Hydroxy isothiocyanates, especially 2-(4-hydroxyphenyl)ethyl isothiocyanate (hITC), were examined for antimicrobial synergism with streptomycin (SM) against Escherichia coli . On the course of those experiments, a peculiar suppression of SM by a low concentration of hITC was observed, besides the antibacterial synergism of hITC with SM . Further, bactericidal activity of SM in physiological saline was reduced by addition of hITC . Time course experiments proved that the antagonistic effect of hITC occurred in an early stage after exposure of bacterial cells to SM. Biosci Biotechnol Biochem, 2003 Aug, 67(8), 1636 - 42 Purification, characterization, and sequencing of a novel type of antimicrobial peptides, Fa-AMP1 and Fa-AMP2, from seeds of buckwheat (Fagopyrum esculentum Moench.); Fujimura M et al.; Novel antimicrobial peptides (AMP), designated Fa-AMP1 and Fa-AMP2, were purified from the seeds of buckwheat (Fagopyrum esculentum Moench.) by gel filtration on Sephadex G75, ion-exchange HPLC on SP COSMOGEL, and reverse-phase HPLC . They were basic peptides having isoelectric points of over 10 . Fa-AMP1 and Fa-AMP2 had molecular masses of 3,879 Da and 3,906 Da on MALDI-TOF MS analysis, and their extinction coefficients in 1% aqueous solutions at 280 nm were 42.8 and 38.9, respectively . Half of all amino acid residues of Fa-AMP1 and Fa-AMP2 were cysteine and glycine, and they had continuous sequences of cysteine and glycine . The concentrations of peptides required for 50% inhibition (IC50) of the growth of plant pathogenic fungi, and Gram-positive and -negative bacteria were 11 to 36 microg/ml . The structural and antimicrobial characteristics of Fa-AMPs indicated that they are a novel type of antimicrobial peptides belonging to a plant defensin family. J Antimicrob Chemother, 2003 Oct, 52(4), 564 - 71 Epub 2003 Sep 01. Considering resistance in systematic reviews of antibiotic treatment; Leibovici L et al.; CONTEXT: Microorganisms resistant to antibiotic drugs are a threat to the health and chances of survival of patients . Systematic reviews on antibiotic drugs that ignore the topic of resistance present readers with a skewed view, emphasizing short-term efficacy or effectiveness while ignoring long-term consequences . OBJECTIVES: To examine whether systematic reviews of antibiotic treatment consider resistance; if not, to find out whether data on resistance were reported in the original trials; and based on that, to offer a framework for taking resistance into account in systematic reviews . DATA SOURCES: The Cochrane Database of Systematic Reviews (the Cochrane Library, 2001, issue 2); and MEDLINE, 1996-2000 . STUDY SELECTION: (i) Systematic reviews or meta-analyses of antimicrobial therapy, published during 1996-2000 . (ii) Randomized, controlled trials abstracted in systematic reviews that addressed a topic highly relevant to antibiotic resistance . DATA EXTRACTION: We examined each systematic review, and each article, to see whether the implications of resistance were discussed; and whether data on resistance were collected . RESULTS: Out of 111 systematic reviews, only 44 (40%) discussed resistance . Ten reviews (9%) planned or performed collection of data on the response of patients with susceptible or resistant isolates . In 22 systematic reviews (20%), collection of data on induction of resistance was planned or performed . The topic of 41 reviews was judged highly relevant to resistance, and these reviews extracted data from 337 articles, out of which we retrieved 279 articles (83%) . In 201 (72%) articles, resistance was discussed or data pertaining to it were collected . Ninety-seven articles (35%) gave actual data on resistance of pathogens to the study drugs, 71 articles (25%) data on efficacy of antibiotic drugs in patients with susceptible and resistant pathogens, and 55 articles (20%) provided data on infection or colonization with resistant strains during treatment . CONCLUSIONS: Most systematic reviews on antibiotic treatment ignored the issue of resistance, although many of the original articles referred to it and some reported relevant data . Reviewers should collect data on resistance and discuss the implications in their discussion and sections concerned with policy implications. Bioorg Med Chem Lett, 2003 Oct 6, 13(19), 3345 - 50 Muraymycins, novel peptidoglycan biosynthesis inhibitors: synthesis and SAR of their analogues; Yamashita A et al.; A series of Muraymycin analogues was synthesized . These analogues showed excellent antimicrobial activity against gram-positive organisms . These analogues also showed excellent inhibitory activity against the target peptidoglycan biosynthesis enzyme MraY, the cell membrane associated transglycosylase responsible for the formation of Lipid II. Mol Microbiol, 2003 Sep, 49(6), 1547 - 63 Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy; Gao LY et al.; Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually . The unusually low permeability of its cell wall contributes to the ability of M . tuberculosis to grow within host macrophages, a property required for pathogenesis of infection . Mycobacterium marinum is an established model for discovering genes involved in mycobacterial infection . Mycobacterium marinum mutants with transposon insertions in the beta-ketoacyl-acyl carrier protein synthase B gene (kasB) grew poorly in macrophages, although growth in vitro was unaffected . Detailed analyses by thin-layer chromatography, nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, infrared spectroscopy, and chemical degradations showed that the kasB mutants synthesize mycolic acids that are 2-4 carbons shorter than wild type; the defect was localized to the proximal portion of the meromycolate chain . In addition, these mutants showed a significant (approximately 30%) reduction in the abundance of keto-mycolates, with a slight compensatory increase of both alpha- and methoxy-mycolates . Despite these small changes in mycolate length and composition, the kasB mutants exhibited strikingly altered cell wall permeability, leading to a marked increase in susceptibility to lipophilic antibiotics and the host antimicrobial molecules defensin and lysozyme . The abnormalities of the kasB mutants were fully complemented by expressing M . tuberculosis kasB, but not by the closely related gene kasA . These studies identify kasB as a novel target for therapeutic intervention in mycobacterial diseases. Mycoses, 2003 Sep, 46(8), 351 - 4 Surgical treatment of tinea capitis in childhood; Thoma-Greber E et al.; Fungal infections of the scalp can cause kerion, pus-filled swellings, that may look like bacterial abscesses . We report on two children who underwent incision and drainage of their kerions under local and general anesthesia . This treatment was inappropriate: it carried the risk associated with general anesthesia and surgery without providing the therapeutic chance linked to adequate antimicrobial chemotherapy . We recommend that children who are present at emergency departments with pus-filled swellings on the scalp should be referred to a dermatology unit where appropriate clinical and laboratory investigations and antifungal treatment can be provided, if considered adequate. Helicobacter, 2003 Aug, 8(4), 310 - 9 A prospective, randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin; Miehlke S et al.; BACKGROUND AND AIM: Failure of primary anti-H . pylori therapy results in a high rate of antimicrobial resistance . Here, we investigated the efficacy of high-dose dual therapy and quadruple therapy as salvage treatments for eradication of H . pylori resistant to both metronidazole and clarithromycin . PATIENTS AND METHODS: Patients with at least one treatment failure and infected with H . pylori resistant to both metronidazole and clarithromycin, were randomized to receive either omeprazole 4 x 40 mg and amoxicillin 4 x 750 mg; or omeprazole 2 x 20 mg, bismuthcitrate 4 x 107 mg, metronidazole 4 x 500 mg and tetracycline 4 x 500 mg . Both regimens were given for 14 days . In cases of persistent infection, a cross-over therapy was performed . RESULTS: Eighty-four patients were randomized . Cure of H . pylori infection was achieved in 31 patients after dual therapy and in 35 patients after quadruple therapy (per protocol: 83.8% (95% CI, 67.9-93.8) and 92.1% (95% CI, 78.6-98.3), respectively (p=0.71); intention to treat: 75.6% (95% CI: 59.7-87.6) and 81.4% (95% CI: 66.6-91.6), respectively (p=0.60)) . Cross-over therapy was performed in six of nine patients, four of whom were cured of the infection . CONCLUSION: Both high-dose dual therapy and quadruple therapy are effective in curing H . pylori infection resistant to both metronidazole and clarithromycin in patients who experienced previous treatment failures. Clin Exp Dermatol, 2003 Sep, 28(5), 549 - 53 Parental knowledge of topical therapies in the treatment of childhood atopic dermatitis; Beattie PE et al.; Poor adherence with therapy is a major cause of treatment failure in atopic dermatitis . Reasons given are multifactorial, and include fear of real or imaginary side-effects, under-prescribing, failure to renew prescriptions on time, lack of time, and child refusal of therapy . Most important, however, is lack of knowledge about treatment, in particular the use of topical corticosteroid (TCS) therapy . We conducted a questionnaire-based study to determine the level of use and knowledge of commonly prescribed TCS preparations amongst parents or carers of 100 children attending paediatric outpatient clinics . Weakly potent TCSs were the most commonly used (86%), but poorly understood . Only 35 (41%) who had used hydrocortisone were aware that it was weakly potent, and 44% graded it as moderately potent . Of 65 who had used the moderately potent TCS clobetasone butyrate 0.05% (Eumovate); Glaxo Wellcome, Uxbridge, UK), 19 (29%) graded it as potent and eight (12%) as weak . Of 50 who had used betamethasone valerate 0.1% (Betnovate); Glaxo Wellcome, Uxbridge, UK), 42% did not grade it as potent . Understanding of TCS/antimicrobial combinations was generally worse . The hydrocortisone 1%/fusidic acid 2% combination (Fucidin H(R); Leo, Risborough, Bucks, UK) was graded as moderate or strong by 88% of the 74 who had used it . Over half (53%) of the 34 using the combination of clobetasone butyrate 0.05%/nystatin 100000 i.u./g tetracycline 3% (Trimovate); Glaxo Wellcome, Uxbridge, UK) assumed that it was a potent TCS . Forty-nine had used Fucibet (betamethasone valerate 0.1%, fusidic acid 2%; Leo, Risborough, Bucks, UK) but 34.5% did not grade it as potent . There was poor knowledge of the strengths of some of the most commonly used TCSs, and all steroid/antimicrobial combinations were perceived as being of greater potency than the constituent steroid alone . Fusidic acid was thought to be a steroid by almost half (46.9%) of the respondents . The packaging of the different products by some pharmaceutical companies is remarkably similar and labelling contains information on the compound and percentage rather than potency of the TCS . This may be a source of confusion . We recommend that manufacturers clearly label TCS products by potency as mild, moderate, potent or very potent and that packaging is sufficiently different for each strength of TCS or emollient to avoid confusion . In order to achieve optimal topical treatment for atopic dermatitis, patients and their carers must receive adequate information and training in how and when to use topical therapies in conjunction wit