AORN J, 2000 Mar, 71(3), 584 - 7, 589-90, 592 passim Moisturizing alcohol hand gels for surgical hand preparation; Jones RD et al.; With the use of novel formulary technology, unique moisturizing hand gels have been developed that offer significant advantages in perioperative and other health care settings . These advantages include the time-saving capabilities of a waterless formulation, the persistence and effectiveness of a surgical scrub, and the moisturization and protective properties of a lotion . Extensive laboratory and clinical studies, involving in vivo antimicrobial activity against resident and transient flora, skin moisturization on normal and dry skin, and compatibility with latex gloves, have supported these advantages . Nondrying alcohol hand gels can be used for antiseptic hand washing, hand scrubs between procedures (i.e., reentry scrubs), brushless surgical scrubs, moisturizers, and glove-donning aids. Dev Comp Immunol, 2000 Jun, 24(4), 381 - 93 Mytilin B and MGD2, two antimicrobial peptides of marine mussels: gene structure and expression analysis; Mitta G et al.; Previous research has shown that mytilins and MGDs are two types of 4-kDa, cysteine-rich, cationic antimicrobial peptides, which are abundant in hemocytes of the mussels, Mytilus galloprovincialis and M . edulis . The expression of the genes encoding these peptides has been analyzed in the hemocytes of animals subjected to various stress factors, as well as during larval development . Variations in gene expression in adult mussels have been tested under conditions of physical stress, bacterial challenge and heat shock . The results suggest that in adult mussels, the MGD2 gene may be over-expressed with physical and temperature stress, but that reduced expression occurs with bacterial challenge . Gene expression during development has been analyzed using different larval and post-larval stages, ranging from 4-day-old veliger larvae to 32-day-old post-larvae . The results show that the expression of both mytilin B and MGD2 is developmentally regulated, but neither gene is expressed in mussels until after larval settlement and metamorphosis . Finally, the genes encoding two isoforms of these peptides have been cloned and sequenced, revealing that both genes contain four exons and three introns. J Appl Microbiol, 2000 Feb, 88(2), 308 - 16 Antimicrobial agents from plants: antibacterial activity of plant volatile oils; Dorman HJ et al.; The volatile oils of black pepper {Piper nigrum L . (Piperaceae)}, clove {Syzygium aromaticum (L.) Merr . & Perry (Myrtaceae)}, geranium {Pelargonium graveolens L'Herit (Geraniaceae)}, nutmeg {Myristica fragrans Houtt . (Myristicaceae), oregano {Origanum vulgare ssp . hirtum (Link) Letsw . (Lamiaceae)} and thyme {Thymus vulgaris L . (Lamiaceae)} were assessed for antibacterial activity against 25 different genera of bacteria . These included animal and plant pathogens, food poisoning and spoilage bacteria . The volatile oils exhibited considerable inhibitory effects against all the organisms under test while their major components demonstrated various degrees of growth inhibition. J Endourol, 2000 Feb, 14(1), 33 - 7 Infection-resistant alloplasts; Darouiche RO; Prosthesis-related infection accounts for nearly half of nosocomial infections, resulting in significant morbidity, mortality, prolonged hospitalization, and higher healthcare costs . Although numerous antimicrobial-coated surfaces have been suggested to guard against prosthesis-related infection, only a few, such as minocylcine plus rifampin, are clinically protective . The differences in clinical efficacy can be attributed at least in part to differences in the magnitude of leaching of the antimicrobial agent off the surface . There is a pressing need to explore the clinical efficacy of antimicrobial surfaces suitable for use in devices intended for long-term use. JAMA, 2000 Mar 22-29, 283(12), 1583 - 90 Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial; Talan DA et al.; CONTEXT: The optimal antimicrobial regimen and treatment duration for acute uncomplicated pyelonephritis are unknown . OBJECTIVE: To compare the efficacy and safety of a 7-day ciprofloxacin regimen and a 14-day trimethoprim-sulfamethoxazole regimen for the treatment of acute pyelonephritis in women . DESIGN: Randomized, double-blind comparative trial conducted from October 1994 through January 1997 . SETTING: Twenty-five outpatient centers in the United States . PATIENTS: Of 378 enrolled premenopausal women aged at least 18 years with clinical diagnosis of acute uncomplicated pyelonephritis, 255 were included in the analysis . Other individuals were excluded for no baseline causative organism, inadequate receipt of study drug, loss to follow-up, no appropriate cultures, and other reasons . INTERVENTIONS: Patients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days (with or without an initial 400-mg intravenous dose) followed by placebo for 7 days (n = 128 included in analysis) vs trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days (with or without intravenous ceftriaxone, 1 g) (n = 127 included in the analysis) . MAIN OUTCOME MEASURE: Continued bacteriologic and clinical cure, such that alternative antimicrobial drugs were not required, among evaluable patients through the 4- to 11-day posttherapy visit, compared by treatment group . RESULTS: At 4 to 11 days posttherapy, bacteriologic cure rates were 99% (112 of 113) for the ciprofloxacin regimen and 89% (90 of 101) for the trimethoprim-sulfamethoxazole regimen (95% confidence interval {CI} for difference, 0.04-0.16; P = .004) . Clinical cure rates were 96% (109 of 113) for the ciprofloxacin regimen and 83% (92 of 111) for the trimethoprim-sulfamethoxazole regimen (95% CI, 0.06-0.22; P = .002) . Escherichia coli, which caused more than 90% of infections, was more frequently resistant to trimethoprim-sulfamethoxazole (18%) than to ciprofloxacin (0%; P<.001) . Among trimethoprim-sulfamethoxazole-treated patients, drug resistance was associated with greater bacteriologic and clinical failure rates (P<.001 for both) . Drug-related adverse events occurred in 24% of 191 ciprofloxacin-treated patients and in 33% of 187 trimethoprim-sulfamethoxazole-treated patients, respectively (95% CI, -0.001 to 0.2) . CONCLUSIONS: In our study of outpatient treatment of acute uncomplicated pyelonephritis in women, a 7-day ciprofloxacin regimen was associated with greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen, especially in patients infected with trimethoprim-sulfamethoxazole-resistant strains. Hosp Med, 2000 Jan, 61(1), 24 - 30 Clinical efficacy and antimicrobial pharmacodynamics; Wise R; Changes in the susceptibility of bacterial pathogens and the availability of new antimicrobial drugs mean that physicians need to understand the underlying pharmacodynamics of each antimicrobial therapy . Antimicrobial pharmacodynamics determine clinical efficacy and should therefore be carefully considered when selecting appropriate antibiotic agents in the therapeutic setting. Akush Ginekol (Sofiia), 1999, 38(3), 61 - 2 {A multicenter study of the antimicrobial effect of Macmiror and Macmiror Complex in the treatment of vaginal infections}; Karag'ozov I et al.; The aim of the present multicentre study was to examine the therapeutic possibilities of the wide-spectrum medicament MACMIROR & MACMIROR COMPLEX for the treatment of the vaginal infections . MATERIALS AND METHODS: The study included 159 nonpregnant women among 15 and 54 years (middle age 35.6) with different by kind and intensity colpitis complaints . The following microbiological characteristic was established: in 26 cases Gardnerella vaginalis, in 46 Candida spp., and in the rest 87-mixed aerobic bacterial flora, with a combination of Gardnerella, yeast and Trichomonas . The treatment of the patients was done in combined scheme: peroral and vaginal administration, simultaneously with local treatment of the partner . The control examination was performed bistagely: on 7-10 day and on 30-40 day . RESULTS: The good clinical and microbiological influence of the treated patients was established, for the first control examination the effect was found in 88.1% and 86.8% and for the second--respectively in 81.1% and 82.4% . CONCLUSIONS: The received results give us a cause to approve, that the combination "Nifuratel and Nystatin" (Macmiror & Macmimor complex) has the good possibilities to influence the mixed forms of vaginal infection. Drugs Aging, 2000 Jan, 16(1), 67 - 80 Bone and joint infections in the elderly: practical treatment guidelines; Mader JT et al.; Two types of haematogenous osteomyelitis that are seen in the elderly are vertebral and long bone osteomyelitis . Osteomyelitis secondary to contiguous foci of infection can occur in older adults without vascular insufficiency (secondary to pressure ulcers) or with vascular insufficiency due to diabetes mellitus or peripheral vascular disease from atherosclerosis . Most cases of osteomyelitis can be reasonably treated with adequate drainage, thorough debridement, obliteration of dead space, wound protection, and antimicrobial therapy . Patients are initially given a broad spectrum antimicrobial that is changed to specific antimicrobial therapy based on meticulous bone cultures taken at debridement surgery or from deep bone biopsies . Surgical management is often required in the treatment of osteomyelitis and includes adequate drainage, extensive debridement of all necrotic tissue, obliteration of dead spaces, stabilisation, adequate soft tissue coverage, and restoration of an effective blood supply . Bone repair and bone mineral density may be significantly retarded and may be corrected by eliminating risk factors, supplementing the diet with calcium, bisphosphonates, and/or vitamin D, and treating with testosterone and/or estrogen when deficient . Sodium fluoride treatment and anabolic steroids may be used as alternatives . Septic arthritis is a medical emergency, and prompt recognition and rapid and aggressive treatment are critical to ensuring a good prognosis . The treatment of septic arthritis includes appropriate antimicrobial therapy and joint drainage . Adverse effects of prescribed antibacterials occur more often in the elderly patient than in young adults . The physician can help to minimise the incidence of adverse effects and improve outcomes by being aware of the principles of clinical pharmacology, the characteristics of specific drugs, and the special physical, psychological and social needs of older patients. J Leukoc Biol, 2000 Mar, 67(3), 335 - 44 A beneficial aspect of a CB1 cannabinoid receptor antagonist: SR141716A is a potent inhibitor of macrophage infection by the intracellular pathogen Brucella suis; Gross A et al.; The psychoactive component of marijuana, delta9-tetrahydrocannabinol (THC) suppresses different functions of immunocytes, including the antimicrobicidal activity of macrophages . The triggering of cannabinoid receptors of CB1 and CB2 subtypes present on leukocytes may account for these effects . We investigated the influence of specific CB1 or CB2 receptor antagonists (SR141716A and SR144528, respectively) and nonselective CB1/CB2 cannabinoid receptor agonists (CP55,940 or WIN 55212-2) on macrophage infection by Brucella suis, an intracellular gram-negative bacteria . None of the compounds tested affected bacterial phagocytosis . By contrast, the intracellular multiplication of Brucella was dose-dependently inhibited in cells treated with 10-500 nM SR141716A and 1 microM SR141716A-induced cells exerted a potent microbicidal effect against the bacteria . SR144528, CP55,940, or WIN 55212-2 did not affect (or slightly potentiated) the growth of phagocytized bacteria . However, CP55,940 or WIN 55212-2 reversed the SR141716A-mediated effect, which strongly suggested an involvement of macrophage CB1 receptors in the phenomenon . SR141716A was able to pre-activate macrophages and to trigger an activation signal that inhibited Brucella development . The participation of endogenous cannabinoid ligand(s) in Brucella infection was discussed . Finally, our data show that SR141716A up-regulates the antimicrobial properties of macrophages in vitro and might be a pharmaceutical compound useful for counteracting the development of intramacrophagic gram-negative bacteria. J Clin Gastroenterol, 2000 Mar, 30(2), 205 - 9 A case of sclerosing cholangitis managed by a percutaneous approach; Tritto G et al.; In 1992, a 61-year-old man who complained of recurrent episodes of fever and jaundice was diagnosed as having sclerosing cholangitis . In the three years that followed, the clinical picture progressively worsened; and, in 1995, the patient was hospitalized again for biliary obstruction . A liver transplantation was excluded because of concomitant severe coronary heart disease . A percutaneous transhepatic cholangiogram showed several critical strictures of the intrahepatic biliary tree and a temporary internal-external biliary drainage was placed to relieve the obstruction . After 40 days, a two-step percutaneous biliary balloon dilation was performed followed by topical steroid treatment through the catheter . After 45 days, the catheter was removed and steroid treatment tapered orally . In the three years that followed, the patient was well . He experienced only about 1-2 episodes of ascending cholangitis per year requiring antimicrobial therapy . Laboratory analysis showed a gradual improvement in hepatic chemistry, serum bilirubin, and erythrocyte sedimentation rate (ESR) . In our patient, the association of percutaneous balloon dilation and topical steroid treatment improved both the clinical and radiological picture, without significant side-effects . This approach should be considered a valuable and cost-effective option in primary sclerosing cholangitis, mainly for patients not eligible for liver transplantation. Fitoterapia, 2000 Apr, 71(2), 193 - 4 Antimicrobial activity of Bryophyllum pinnatum leaves; Akinpelu DA; Bryophyllum pinnatum leaf 60% methanolic extract was found to inhibit the growth of five out of eight bacteria used, at a concentration of 25 mg/ml. Fitoterapia, 2000 Apr, 71(2), 187 - 9 Antimicrobial activity of methanolic extract of Solanum torvum fruit; Chah KF et al.; The methanolic extract of Solanum torvum fruit showed a wide spectrum of antimicrobial activities against human and animal clinical isolates. Fitoterapia, 2000 Apr, 71(2), 179 - 82 Antimicrobial activity of Trichilia heudelotti leaves; Aladesanmi AJ et al.; Diterpenes and phenolic acids, including the new compounds 12 beta-hydroxysandaracopimar-15-ene (4) and 2-propionoxy-beta-resorcylic acid (8) have been isolated from Trichilia heudelotti leaves . The methanol extract showed antimicrobial activity concentrated in the ethyl acetate fraction and some of its constituents. Fitoterapia, 2000 Apr, 71(2), 176 - 8 Antimicrobial properties of Thonningia sanguinea root extracts; Ohiri FC et al.; The aqueous and methanolic extracts of Thonningia sanguinea root, as well as seven fractions obtained by PTLC from the methanol extract, have been shown to possess varying degrees of antimicrobial activity. J Exp Med, 2000 Mar 20, 191(6), 937 - 48 Self-recognition of CD1 by gamma/delta T cells: implications for innate immunity; Spada FM et al.; The specificity of immunoglobulins and alpha/beta T cell receptors (TCRs) provides a framework for the molecular basis of antigen recognition . Yet, evolution has preserved a separate lineage of gamma/delta antigen receptors that share characteristics of both immunoglobulins and alpha/beta TCRs but whose antigens remain poorly understood . We now show that T cells of the major tissue gamma/delta T cell subset recognize nonpolymorphic CD1c molecules . These T cells proliferated in response to CD1+ presenter cells, lysed CD1c+ targets, and released T helper type 1 (Th1) cytokines . The CD1c-reactive gamma/delta T cells were cytotoxic and used both perforin- and Fas-mediated cytotoxicity . Moreover, they produced granulysin, an important antimicrobial protein . Recognition of CD1c was TCR mediated, as recognition was transferred by transfection of the gamma/delta TCR . Importantly, all CD1c-reactive gamma/delta T cells express V delta 1 TCRs, the TCR expressed by most tissue gamma/delta T cells . Recognition by this tissue pool of gamma/delta T cells provides the human immune system with the capacity to respond rapidly to nonpolymorphic molecules on professional antigen presenting cells (APCs) in the absence of foreign antigens that may activate or eliminate the APCs . The presence of bactericidal granulysin suggests these cells may directly mediate host defense even before foreign antigen-specific T cells have differentiated. Eur J Dermatol, 2000 Apr-May, 10(3), 184 - 9 Lupus erythematosus tumidus and chronic discoid lupus erythematosus in carriers of X-linked chronic granulomatous disease; Rupec RA et al.; Two Caucasian carriers for chronic granulomatous disease (CGD) developed cutaneous lupus erythematosus (LE) with clinically and morphologically characteristic appearance for chronic discoid lupus erythematosus (DLE) and lupus erythematosus tumidus (LET) . Direct immunofluorescent examinations and ANA titers were positive in both young women . No systemic involvement due to the ACR criteria was evident . Their sons suffered from X-linked cytochrome-b negative CGD . The diagnosis of CGD was based on measurement of oxidative burst activity by nitroblue tetrazolium (NBT) slide test and by flow cytometry using dihydrorhodamine 123 (DHR) . The absence of cytochrome b558 in neutrophilic granulocytes was confirmed photometrically and by flow cytometry using the 7D5 monoclonal antibody against cytochrome b . We report for the first time the association of the photosensitive LE subtype LET and the X-linked CGD carrier state . Tissue damage by UV radiation and a reduced antimicrobial capacity may lead to recurrent immune stimulation and may together with genetic predisposition explain the occurrence of cutaneous LE in female carriers of CGD. Phytochemistry, 2000 Mar, 53(5), 555 - 64 Distribution of morphinan and benzo{c}phenanthridine alkaloid gene transcript accumulation in Papaver somninferum; Huang FC et al.; The opium poppy Papaver somniferum L . produces the antimicrobial benzo{c}phenanthridine alkaloid sanguinarine and the narcotic analgesic morphinan alkaloid morphine . Transcripts of three genes of alkaloid biosynthesis in P . somniferum in developing seedlings, mature plants and plant cell suspension culture were monitored for temporal/spatial or for methyl jasmonate-induced accumulation by RNA gel blot analysis . These genes encoded (S)-N-methylcoclaurine 3'-hydroxylase (CYP80B1) that is common to morphine and sanguinarine biosynthesis, the berberine bridge enzyme (BBE) that lies on the pathway to sanguinarine, and codeinone reductase (COR) the penultimate enzyme of morphine biosynthesis . In developing P . somniferum seedlings, the morphine precursor thebaine was present throughout the first twenty days of germination . In contrast, sanguinarine was present in detectable quantities only after day five after germination and continued to increase at least until day twenty . Accumulation of cyp80b1, bbe1 and cor1 gene transcripts paralleled these differences . In the mature poppy plant, cyp80b1, bbe1 and cor1 gene transcripts were detected in the root, the stem, the leaf lamina and the leaf mid rib . Only cyp80b1 and cor1, however, were found in the flower bud and the capsule . Consistent with the fact that sanguinarine accumulation, but not that of morphine, can be induced in opium poppy cell suspension culture by addition of methyl jasmonate to the culture medium, cyp80b1 and bbe1, but not cor1 transcript accumulated in response to elicitor treatment. Int J Antimicrob Agents, 2000 Jan, 13(3), 155 - 68 Targeted delivery of antibiotics using liposomes and nanoparticles: research and applications; Pinto-Alphandary H et al.; This review examines current technologies for increasing the bioavailability of antibiotics by means of liposomes or nanoparticles . The main focus is on liposomes . These carriers were preferentially developed because their composition is compatible with biological constituents . Biodegradable polymers in the form of colloidal particles have also been used and show promise for future applications in antimicrobial chemotherapy . The in vivo behaviour of both types of carriers and consequently their therapeutic potential, are determined by their route of administration . Conventional carrier strategies permit the mononuclear phagocyte system to be targeted by intravenous injection of antibiotics . Stealthy strategies avoid major uptake by these cells and extend the systemic presence of these carriers . The purpose of this review is to provide background information in antibiotic targeting gathered from papers published over the last twenty years . It seems clear that such drug carriers (liposomes, nanoparticles) allow increased drug concentration at infected sites but reduce drug toxicity. Br Med Bull, 1999, 55(2), 387 - 400 Pathogen virulence genes--implications for vaccines and drug therapy; Tang C et al.; The emergence and spread of bacteria resistant to antimicrobial drugs is a major public health problem with a growing number of infections becoming virtually untreatable . There is a need to develop interventions both to prevent and to treat diseases caused by multi-resistant microbes . We review some recently developed methods (including whole genome nucleotide sequencing projects) to study bacterial pathogenesis, and discuss how knowledge gained from understanding the molecular mechanisms of disease can be applied to combat the threat of infectious diseases. Pharmazie, 2000 Feb, 55(2), 87 - 93 Synthesis and antimicrobial activity of acyclo C-nucleosides: 3-(alditol-1-yl)-7-oxo-5-phenyl-1,2,4-triazolo{4,3-a}pyrimidines; Shaban MA et al.; Condensation of 2-hydrazino-4-oxo-6-phenylpyrimidine (1) with aldopentoses 2a-d or aldohexoses 2e-g gave the corresponding aldehydo-sugar (4-oxo-6-phenylpyrimidin-2-yl)hydrazones 3a-g which were acetylated to the corresponding poly-O-acetyl-aldehydo-sugar (3-acetyl-4-oxo-6-phenylpyrimidin-2-yl)hydrazones 4a-g . The latter compounds underwent oxidative cyclization with bromine in acetic acid and in the presence of sodium acetate to the corresponding 8-acetyl-3- (poly-O-acetyl-alditol-1-yl)-7-oxo-5-phenyl-1,2,4-triazolo{4,3-a}pyrimid ines 6a-g . Compounds 6a-g were also obtained by consecutive one-pot oxidative cyclization/acetylation in which the parent hydrazones 3a-g were treated with bromine/acetic acid/sodium acetate followed by acetic anhydride . Deacetylation of 6a-g with ammonium hydroxide in methanol gave the title compounds 7a-g . The antibacterial and antifungal activities of compounds 3c, 3f, 7c and 7f are reported. Food Chem Toxicol, 2000 Apr, 38(4), 319 - 23 Lack of oestrogenic effects of food preservatives (parabens) in uterotrophic assays; Hossaini A et al.; The oestrogenic activity of the parabens, methyl-, ethyl- and propyl p-hydroxybenzoate, widely used as antimicrobials in food, and butyl p-hydroxybenzoate, which is used in cosmetic products, and their shared main metabolite p-hydroxybenzoic acid was investigated in a mouse uterotrophic assay . Immature B6D2F1 mice were treated with oral or subcutaneous doses of the test compounds for three consecutive days . p-Hydroxybenzoic acid and butyl p-hydroxybenzoate were also tested by the subcutaneous route in a rat uterotrophic assay . A significant increase in the uterus weight at day 4 was considered an oestrogenic effect . In the mouse assay, none of the compounds tested produced any oestrogenic response at dose levels up to 100mg/kg body weight per day, for ethyl p-hydroxybenzoate even at a dose level of 1000mg/kg body weight per day . In immature Wistar rats, subcutaneous administration of butyl p-hydroxybenzoate produced a weak oestrogenic response at 600mg/kg body weight per day. Immunol Lett, 2000 Mar 1, 71(3), 171 - 6 Nitric oxide induced expression of stress proteins in virulent and avirulent promastigotes of Leishmania donovani; Adhuna A et al.; Intracellular survival and replication of Leishmania donovani inside macrophage is essential for establishment of the disease . Cytokines play an important role in this process through activation or inhibition of macrophage antimicrobial activity . Nitric oxide (NO) has been demonstrated to be the principal effector molecule mediating intracellular killing of Leishmania . We have examined the effect of NO and various other cytokines on stress protein synthesis by promastigotes of L . donovani virulent and avirulent strains . Virulent promastigotes exposed to NO showed appreciable increase in relative synthesis of HSPs 83, 70 and 65 . The overexpression of HSPs on exposure of parasite to NO was observed to be more pronounced at 37 degrees C than at 24 degrees C . In contrast, the avirulent promastigotes responded by an increase in relative synthesis of HSP70 alone at 37 degrees C . Furthermore, treatment of promastigotes of L . donovani with gammaIFN, TGF-beta or IL-4 did not significantly alter the stress proteins expression . The overexpression of HSPs in promastigotes of L . donovani in response to sublethal doses of NO suggests that HSPs may be playing a protective role for parasite survival in the mammalian host . This is further supported by the observation that a significantly higher induction of HSPs is seen in the virulent as compared to the avirulent strain of L . donovani. J Antibiot (Tokyo), 2000 Jan, 53(1), 1 - 11 Novel streptopyrroles from Streptomyces rimosus with bacterial protein histidine kinase inhibitory and antimicrobial activities; Trew SJ et al.; A series of halogenated pyrrolo {2,1-b} {1,3} benzoxazines (1 approximately 9) was isolated from fermentations of an actinomycete strain X10/78/978 (NCIMB40808), identified as Streptomyces rimosus, during a microbial extract screening programme to identify inhibitors of bacterial histidine kinase . The structures of these compounds were elucidated by spectroscopic methods including the HMQC, HMBC and INADEQUATE NMR experiments . The structure of 1 was confirmed by X-ray crystallographic studies . Compounds 5 and 6 were produced in fermentations in the presence of NaBr and NaI respectively . The most abundant member of the series, streptopyrrole, 1, inhibited the nitrogen regulator II (NRII) histidine kinase from Escherichia coli with an IC50 of 20 microM and exhibited antimicrobial activity against a range of bacteria and fungi. Antimicrob Agents Chemother, 2000 Apr, 44(4), 1004 - 9 Risk factors for recovery of ampicillin-sulbactam-resistant Escherichia coli in hospitalized patients; Kaye KS et al.; Ampicillin-sulbactam resistance in Escherichia coli is an emerging problem . This study determined risk factors for the recovery of ampicillin-sulbactam-resistant E . coli in hospitalized patients . A case-control design was used to compare two groups of case patients with control patients . The first group of case patients consisted of patients from whom nosocomially acquired ampicillin-sulbactam-resistant E . coli strains were isolated, and the second group of case patients consisted of patients from whom ampicillin-sulbactam-susceptible E . coli strains were isolated . Control patients were a random selection among 5% of all patients admitted during the same time period . Risk factors analyzed included antimicrobial drug exposure, comorbid conditions, and demographics . Univariate and multivariate analyses were performed . Ampicillin-sulbactam-resistant E . coli strains were isolated from 175 patients, and ampicillin-sulbactam-susceptible E . coli strains were isolated from 577 patients . Nine hundred thirty-four control patients were selected . Exposure to penicillin antibiotics as a class and to ampicillin and ampicillin-sulbactam individually were the only significant, independent risk factors associated with the isolation of ampicillin-sulbactam-resistant E . coli (odds ratio {OR} = 2.32 {P < 0.001}, OR = 3.04 {P = 0.02}, and OR = 1.72 {P = 0.04}, respectively), but they were not associated with the isolation of ampicillin-sulbactam-susceptible E . coli . Interestingly, exposure to piperacillin-tazobactam tended to protect against the isolation of E . coli strains resistant to ampicillin-sulbactam, but this did not reach statistical significance (OR = 0.13; P = 0.11). Clin Infect Dis, 2000 Mar, 30(3), 444 - 53 Mycobacterium terrae: case reports, literature review, and in vitro antibiotic susceptibility testing; Smith DS et al.; Mycobacterium terrae infection can cause debilitating disease that is relatively resistant to antibiotic therapy . Two cases are presented, and data from an additional 52 reports from the literature are reviewed . Tenosynovitis of the upper extremity, often following trauma, was the most commonly reported presentation (59% of cases), with pulmonary disease occurring in an additional 26% of cases . Underlying medical problems were absent (44%) or not reported (28%) in 72% of the cases . One-half of the patients with upper extremity tenosynovitis were treated with local or systemic corticosteroids, before microbiological identification . Only one-half of the patients with tenosynovitis who were followed up for 6 months had clinical improvement or were cured . The other one-half of the patients required repeated debridement, tendon extirpation, or amputation . The best antimicrobial therapy for M . terrae infection is unknown but might include a macrolide antibiotic plus ethambutol and one other effective drug for at least 12 months after clinical response . Parenteral treatment with an aminoglycoside and surgery may be useful in selected cases. Arch Ophthalmol, 2000 Mar, 118(3), 418 - 21 Traumatic Acremonium atrogriseum keratitis following laser-assisted in situ keratomileusis; Read RW et al.; A 52-year-old man underwent bilateral laser-assisted in situ keratomileusis . Eight months later, he sustained a penetrating corneal injury to the left eye . A dense white infiltrate, unresponsive to antimicrobial therapy, developed in the corneal stroma . Corneal biopsy and eventual penetrating keratoplasty were performed, and both specimens demonstrated fungal elements with branching, septate hyphae . Culture identified the organism as Acremonium atrogriseum . Histopathologic features of this organism and its differentiation from other, more common fungal organisms are discussed herein. Ophthalmologica, 2000, 214(2), 111 - 4 Tolerance of N-chlorotaurine, a new antimicrobial agent, in infectious conjunctivitis - a phase II pilot study; Nagl M et al.; N-Chlorotaurine (NCT) is an endogenous microbicidal oxidant . This open pilot study (phase IIa) with 9 patients was done to gain first knowledge on the tolerance of NCT in infectious conjunctivitis . By application of 1% NCT 5 times a day, no adverse effects could be observed . All 6 subjects with bacterial conjunctivitis were cured within 3-5 days . Two subjects with epidemic keratoconjunctivitis were treated for 7-10 days and 1 subject with herpes simplex blepharitis for 3 days with no rapid improvement but probable mitigation of inflammation . Therefore, NCT seems to be useful in the treatment of infectious conjunctivitis, and further investigation on its therapeutic efficacy is suggested . J Chemother, 1999 Dec, 11(6), 577 - 80 Antimicrobial prophylaxis in obstetric and gynecological surgery; Giuliani B et al.; A major problem in obstetric and gynecological surgery, especially following cesarean section in labor, total vaginal or abdominal hysterectomy, or myomectomy, is postoperative wound infection . Consequently, the use of antimicrobial prophylaxis for cesarean section and for gynecological surgery has been advocated and shown to be effective in reducing postoperative morbidity, costs and duration of hospitalization . We reviewed 1021 patients who underwent cesarean section (597 elective, 424 emergency) and 814 gynecological patients undergoing abdominal (373) or vaginal (248) hysterectomy and myomectomy (193) between 1997-98 in the Obstetrics and Gynecology Clinic of the University of Florence . Before surgery 83.6% of obstetric and 75.1% of gynecological patients received 1 or 2 g of a first or second generation cephalosporin i.v . as a single-dose regimen at induction of anesthesia and sometimes a second postoperative dose . 1.5% of obstetric surgical patients had wound infection, as did 2.8% of gynecological surgery patients, with a mean postoperative hospital stay of 8 days . The short-term perioperative antimicrobial prophylaxis with cephalosporins is useful and provides the benefit of minimal toxicity and risk of chemoresistance. J Chemother, 1999 Dec, 11(6), 565 - 72 Antimicrobial prophylaxis in surgery: the role of pharmacokinetics; Novelli A; Even though surgical infection rates have decreased dramatically during the past 25 years, morbidity and mortality of infection in surgical treatment remains substantial . From a pharmacological point of view, the key factor of the efficacy of antibiotic prophylaxis is to attain bactericidal levels of antibiotic in serum and tissues (target site) during the whole intraoperative and early postoperative period . The success of antibiotic prophylaxis is assured only when the chosen antibiotic with a targeted spectrum and high antimicrobial efficacy is available at the critical moment, at the correct site and in sufficiently high concentration to prevent bacterial contamination of the surgical area . It would be desirable for reasons of convenience and cost if a single preoperative administration were sufficient . The pharmacokinetics and the half-life of antibiotics in the serum are directly related to the duration of activity of antibiotic in the tissue . Antibiotics with longer half-lives maintain levels in the tissues for longer periods than do antibiotics with shorter half-lives and they cover with a single dose the time required for prophylaxis even for longer operations . Finally, the application of the pharmacokinetic properties of antibiotics to surgical prophylaxis can provide the surgeon with certainty that adequate coverage and protection with antibiotics are achieved before and throughout the operation. J Chemother, 1999 Dec, 11(6), 556 - 64 Is single-dose antibiotic prophylaxis sufficient for any surgical procedure? Esposito S. The objective of perioperative prophylaxis is to prevent postoperative infections, which are the primary cause of morbidity and mortality in patients undergoing surgery today . One cannot predict with certainty when bacterial contamination at the operative site may occur during surgery . Furthermore, it has been suggested that the period of highest risk may actually be at the end, rather than at the beginning, of the operation . Therefore, the effect of antimicrobial prophylaxis ideally should cover the entire perioperative "period of risk" . It should be remembered that the period of risk for postoperative infection may last substantially longer than the actual surgical procedure . The duration of the risk period also may vary based on a number of other factors, such as the age and general condition of the patient, presence of concomitant disease, amount of blood loss during surgery, and number of blood transfusions required . Antimicrobial prophylaxis that provides coverage throughout the entire perioperative period of risk will reduce not only the risk of wound infections but may also reduce the danger of other types of infectious complications . Numerous clinical studies have clearly shown that appropriately-timed "single shot" prophylaxis is as effective as multiple-dose prophylaxis . This paper considers the evolution of this therapeutic intervention and reviews the opportunities available for antibiotic prophylaxis in surgery, with particular attention to the long-acting cephalosporin, ceftriaxone. J Chemother, 1999 Dec, 11(6), 551 - 5 Short-term prophylaxis in clean-contaminated surgery; DiPiro JT; Postoperative infections are not consistently controlled by current practice measures . From a recent study of 12,384 patients, postoperative infection occurred in 22% of colorectal procedures and 25% of upper gastrointestinal procedures . Infections were associated with a higher death rate, longer hospitalization, and more intense post-discharge care . Control of infections for clean-contaminated procedures requires effective bowel cleansing when appropriate, meticulous surgical technique, and timely antimicrobial administration . Many patients undergoing clean-contaminated surgery do not receive properly timed antimicrobials . Although the comparative value of oral (neomycin and erythromycin) or parenteral antimicrobials for colon surgery remains an unresolved issue, the combination can be beneficial for many colorectal operations . Third generation cephalosporins are not consistently more effective than older agents such as cefoxitin and increase bacterial resistance . Improper antimicrobial timing is one of the most common problems with surgical prophylaxis and is fully under the control of the surgeon . To maximize benefits of antimicrobial prophylaxis, systems should be devised to assure timely administration. J Chemother, 1999 Dec, 11(6), 530 - 5 Antibiotic use and microbial resistance in intensive care units: impact of computer-assisted decision support; Burke JP et al.; As part of our integrated hospital information system (the HELP system), we developed computer-assisted decision support programs for antimicrobial prescribing that are available at bedside terminals throughout our 520-bed community hospital . Recently, options have been added to allow direct physician order entry of anti-infective agents in the shock-trauma intensive care unit (STRICU) . Physicians prescribed the computer-suggested regimens for 46% but followed the suggested dose and interval for 93% of the orders during a 1-year study period . In comparison to a 2-year pre-intervention period, improved drug selection and reductions in adverse drug events and costs were seen . Antimicrobial resistance patterns for nosocomial gram-negative isolates remained stable or improved in the STRICU over an 11-year period of computer-assisted antibiotic management . We conclude that strategies for optimizing antimicrobial prescribing have the potential to stabilize resistance and reduce costs by encouraging heterogeneous prescribing patterns, use of local antimicrobial susceptibility patterns to inform empiric drug selection, and reduced "tonnage" of antibiotic use. J Chemother, 1999 Dec, 11(6), 426 - 39 Antimicrobial action and pharmacokinetics/pharmacodynamics: the use of AUIC to improve efficacy and avoid resistance; Schentag JJ; In in-vitro and in animal models, antibiotics show good relationships between concentration and response, when response is quantified as the rate of bacterial eradication . The strength of these in-vitro relationships promises their utility for dosage regimen design and predictable cure of human infections . Resistance is also predictable from these parameters, fostering a rational means of using dosing adjustments to avoid or minimize the development of resistant organisms . Newly developed computerized methods for the quantitation of susceptibility allow testing of integrated kinetic-susceptibility models in patients . Our attention has focused recently on fluoroquinolones, since they are relatively non-toxic and provide the necessary range of dosage needed to elucidate correlations between concentration and response in the Intensive Care Unit patient . Studies conducted in patients with nosocomial gram-negative pneumonia reveal good correlations between bacterial eradication and integration of concentration with bacterial susceptibility . In patients, the best correlation parameters are time over MIC, and the ratio of 24-hour AUC to MIC (AUIC) . Patients with serious infections like nosocomial pneumonia require bactericidal antimicrobial activity . Studies in our laboratory demonstrate that the minimum effective antimicrobial action is an area under the inhibitory titer (AUIC) of 125, where AUIC is calculated as the 24-hour serum AUC divided by the MIC of the pathogen . This target AUIC may be achieved with either a single antibiotic or it can be the sum of AUIC values of two or more antibiotics . There is considerable variability in the actual AUIC value for patients when antibiotics are given in their usually recommended dosages . Examples of this variance will be provided using aminoglycosides, fluoroquinolones, beta-lactams, macrolides and vancomycin . The achievement of minimally effective antibiotic action, consisting of an AUIC of at least 125, is associated with bacterial eradication in about 7 days for beta-lactams and quinolones . When AUIC is increased to 250, the quinolone ciprofloxacin (which displays in vivo concentration dependent bacterial killing) can eliminate the bacterial pathogen in 1-2 days . Beta lactams, even when dosed to an AUIC of 250, often require longer treatment duration to eliminate the bacterial pathogen, because the in vivo bacterial killing rate is slower with beta-lactams than with the quinolones . This remains true even at AUIC values of 250 for both compounds, which is theoretically identical dosing . Antibiotic activity indices allow clinicians to evaluate individualized patient regimens . Furthermore, antibiotic activity is a predictable clinical endpoint with predictable clinical outcome . This value is also highly predictive of the development of bacterial resistance . Antimicrobial regimens that do not achieve an AUIC of at least 125 cannot prevent the selective pressure that leads to overgrowth of resistant bacterial sub-populations . Indeed, there is considerable anxiety that conventional respiratory tract infection management strategies, which prescribe antibacterial dosages that may attain AUIC values below 125, are contributing to the pandemic rise in bacterial resistance levels. Arzneimittelforschung, 2000 Feb, 50(2), 154 - 7 Synthesis of 3-substituted phenacyl-5-{2-phenyl-4H-4-oxo-1-benzopyran-6- yl)methylenyl}-thiazolidine-2,4-diones and evaluation of their antimicrobial activity; Ayhan-Kilcigil G et al.; Synthesis and physico-chemical properties of two 3-substituted phenacyl-thiazolidine-2,4-diones (2c-d) and four 3-substituted phenacyl-5-{2-phenyl-4H-4-oxo-1-benzopyran-6-yl)methyl-enyl}-thiazolidin e- 2,4-diones (4a-d) are described . These products were synthesized by Knoevenagel reaction from flavone-6-carboxaldehyde (3) and 3-(substituted phenacyl)- thiazolidine-2,4-diones (2a-d) . Antibacterial and antifungal activities were investigated for these compounds. Injury, 2000 May, 31(4), 233 - 7 Intracranial infection as a common complication following war missile skull base injury; Splavski B et al.; The purpose of this paper is to stress the importance of clinical observation, the appropriate antimicrobial therapy, and early surgery in the management of intracranial infection following war missile penetrating skull base injury . There were 21 skull base missile injuries treated surgically in a 4-year period . Careful removal of devitalised brain tissue with dural closure was performed with all patients to prevent the development of intracranial infection . Subsequent clinical and radiological surveillance was performed to detect evidence of infection and abscess formation if fragments were left in place . Broad range antibiotic coverage, and the antioedematous agents were applied in the early postoperative period . Infection about the brain was seen in four cases . We recorded three cases of brain abscess formation, while one patient developed bacterial meningitis . The incidence of infectious complications was relatively high in our series . After the organisms causing infection were known, treatment was modified to be as specific as possible . It was not necessary to reoperate on intracranially retained foreign bodies and fragments since they did not increase the infection rate . However, repeated surgery is necessary for a brain abscess. Science, 2000 Mar 17, 287(5460), 1973 - 6 Harnessing the power of the genome in the search for new antibiotics; Rosamond J et al.; Over the past 40 years, the search for new antibiotics has been largely restricted to well-known compound classes active against a standard set of drug targets . Although many effective compounds have been discovered, insufficient chemical variability has been generated to prevent a serious escalation in clinical resistance . Recent advances in genomics have provided an opportunity to expand the range of potential drug targets and have facilitated a fundamental shift from direct antimicrobial screening programs toward rational target-based strategies . The application of genome-based technologies such as expression profiling and proteomics will lead to further changes in the drug discovery paradigm by combining the strengths and advantages of both screening strategies in a single program. Immunol Rev, 2000 Feb, 173, 27 - 38 The innate immune response of the respiratory epithelium; Diamond G et al.; The respiratory epithelium maintains an effective antimicrobial environment to prevent colonization by microorganisms in inspired air . In addition to constitutively present host defenses which include antimicrobial peptides and proteins, the epithelial cells respond to the presence of microbes by the induction two complementary parts of an innate immune response . The first response is the increased production of antimicrobial agents, and the second is the induction of a signal network to recruit phagocytic cells to contain the infection . Inflammatory mediators released by the recruited cells as well as from the epithelium itself further induce the expression of the antimicrobial agents . The result is an effective prevention of microbial colonization . The epithelial cells recognize the pathogen-associated patterns on microbes by surface receptors such as CD14 and Toll-like receptors . Subsequent signal transduction pathways have been identified which result in the increased transcription of host defense response genes . Diseases such as cystic fibrosis, or environmental exposures such as the inhalation of air pollution particles, may create an environment that impairs the expression or activity of the host defenses in the airway . This can lead to increased susceptibility to airway infections. Immunol Rev, 2000 Feb, 173, 17 - 26 The role of nitric oxide in innate immunity; Bogdan C et al.; Type 2 nitric oxide synthase (iNOS or NOS2) was originally described as an enzyme that is expressed in activated macrophages, generates nitric oxide (NO) from the amino acid L-arginine, and thereby contributes to the control of replication or killing of intracellular microbial pathogens . Since interferon (IFN)-gamma is the key cytokine for the induction of NOS2 in macrophages and the prototypic product of type 1 T-helper cells, high-level expression of NOS2 has been regarded to be mostly restricted to the adaptive phase of the immune response . In this review, we summarize data that demonstrate a prominent role of NOS2/NO also during innate immunity . During the early phase of infection with the intracellular pathogen Leishmania major, focally expressed NOS2/NO not only exerts antimicrobial activities but also controls the function of natural killer cells and the expression of cytokines such as IFN-gamma or transforming growth factor-beta . Some of these effects result from the function of NOS2/NO as an indispensable co-factor for the activation of Tyk2 kinase and, thus, for interleukin-12 and IFN-alpha/beta signaling in natural killer cells. Ned Tijdschr Geneeskd, 2000 Feb 26, 144(9), 409 - 12 {New developments in the treatment of diabetic foot ulcers}; Bakker K et al.; Diabetic foot ulcers are frequent: 12,000 Dutch diabetes patients have such an ulcer . The ulcers have a multifactorial aetiology: polyneuropathy, biomechanical stress, infection, deficient footwear and to a less extent ischaemia are the major factors . The principles of ulcer treatment are relief of pressure, restoration of skin perfusion, treatment of infection, intensive wound care, metabolic control, treatment of comorbidity, and instruction of the patient . Wound healing is slow . The impaired wound healing is probably caused by deficiencies in local growth factors, changes in the extracellular matrix, diminished fibroblast function, decreased antimicrobial activity of leukocytes and disturbances in the macro- and microcirculation . In recent years several new treatment strategies have been developed to stimulate wound healing in diabetic foot ulcers . These (partly experimental) treatments include: topical growth factors, extracellular matrix products, bioengineered human skin, granulocyte colony stimulating factor and hyperbaric oxygen therapy . In particular recombinant human platelet derived growth factor (becaplermin) has proved to be clinically effective in chronic neuropathic foot ulcer and has been approved in the Netherlands. Semin Neurol, 1999, 19(2), 165 - 76 Clinical features and treatment interventions for human immunodeficiency virus-associated neurologic disease in children; Mintz M; HIV-1 infection in children and adolescents can cause progressive neurologic disease, affective brain growth, motor function, and neurodevelopment . In addition, myelopathies, neuropathies, myopathies, strokes, and psychiatric or behavioral manifestations can be a result of HIV-1 infection, OI, or toxicities of treatment interventions . CNS OI are important causes of morbidity and mortality, often mimicking the HIV-1 associated neurologic syndromes . Psychometric, clinical, neuroradiologic, and laboratory testing are valuable for diagnostic and treatment decisions . The cornerstone of treating HIV-1-associated neurologic disease is providing an effective regimen of antiretroviral drugs to reduce the viral burden . It is also necessary to provide rehabilitation, optimize nutrition, supply appropriate antimicrobial prophylaxis against OI, minimize pain, and treat neurobehavioral or psychiatric complications . Efforts at preventing HIV-1 infection are important for diminishing and allaying the growth of this international pandemic. Am J Med, 2000 Mar 6, 108 Suppl 4a, 131S - 138S Esophageal biopsy for the diagnosis of gastroesophageal reflux-associated otolaryngologic problems in children; Yellon RF et al.; Recently, gastroesophageal reflux (GER) has been found to contribute to many types of otolaryngologic pathology in infants and children . The complaints may be intermittent and unresponsive to usual therapies, such as antimicrobial treatments . A high index of suspicion for GER and for the concept of "silent" GER (GER without overt symptoms) is necessary for accurate diagnosis and treatment of otolaryngologic manifestations of GER in these patients . In this prospective historical cohort study, the records were reviewed from 101 children who underwent esophagoscopy and biopsy as a diagnostic test for GER at the time of other otolaryngologic procedures . Significant associations were found between the presence of histologic esophagitis and asthma, recurrent croup, cough, apnea, sinusitis, stridor, laryngomalacia, subglottic stenosis, posterior glottic erythema, and posterior glottic edema . There were no complications . Esophageal biopsy is a rapid, safe and effective diagnostic test for GER that should be considered at the time of other procedures in children with selected GER-associated problems. Dev Comp Immunol, 2000 Mar-Apr, 24(2-3), 355 - 65 Avian cytokines - the natural approach to therapeutics; Lowenthal JW et al.; While the effective use of antibiotics for the control of human disease has saved countless lives and has increased life expectancy over the past few decades, there are concerns arising from their usage in livestock . The use of antibiotic feed additives in food production animals has been linked to the emergence in the food chain of multiple drug-resistant bacteria that appear impervious to even the most powerful antimicrobial agents . Furthermore, the use of chemical antimicrobials has led to concerns involving environmental contamination and unwanted residues in food products . The imminent banning of antibiotic usage in livestock feed has intensified the search for environmentally-friendly alternative methods to control disease . Cytokines, as natural mediators and regulators of the immune response, offer exciting new alternatives to conventional chemical-based therapeutics . The utilisation of cytokines is becoming more feasible, particularly in poultry, with the recent cloning of a number of avian cytokine genes . Chickens offer an attractive small animal model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock . In this report we will review the status of avian cytokines and focus on our recent studies involving the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter. Trans R Soc Trop Med Hyg, 1999 Nov-Dec, 93(6), 659 - 61 Antimicrobial susceptibility test of Helicobacter pylori isolated from Jos, Nigeria; Ani AE et al.; Fifty-five strains of Helicobacter pylori isolated from November 1997 until October 1998 from 33 female and 22 male adults attending for endoscopy at the Evangel Hospital, Jos, Nigeria were assayed for antibiotic susceptibility to amoxycillin, clarithromycin, metronidazole and tetracycline by the E-test strip method . Minimum inhibitory concentration (MIC) within the attainable peak serum concentrations for each drug was used as the parameter to determine the susceptibility of H . pylori . The results showed 100% susceptibility for amoxycillin, 89.0% for tetracycline, 87.3% for clarithromycin and 60% for metronidazole . The MIC50 and MIC90 values were: 0.016 microgram/mL and 0.75 microgram/mL for amoxycillin, 0.016 microgram/mL and 2 micrograms/mL for clarithromycin, 0.094 microgram/mL and 12 micrograms/mL for tetracycline, and 2 micrograms/mL and > 48 micrograms/mL for metronidazole . The MIC90 values for metronidazole (> 48 micrograms/mL) and tetracycline (12 micrograms/mL) were in each case higher than the break-point value (peak serum concentrations) of 8 micrograms/mL for metronidazole and 3 micrograms/mL for tetracycline . This pattern of resistance to metronidazole and tetracycline has to be considered when therapeutic regimens against H . pylori contain either or both drugs. J Food Prot, 2000 Mar, 63(3), 404 - 7 Antioxidative/Antimicrobial effects of galangal and alpha-tocopherol in minced beef; Cheah PB et al.; The antioxidant and microbial stabilities of galangal (Alpinia galanga) extract in raw minced beef were examined at 4 +/- 1 degree C . Raw minced beef containing galangal extracts (0 to 0.10%, wt/wt) were prepared . Lipid oxidation during refrigerated storage was assessed by monitoring malonaldehyde formation, using the thiobarbituric acid reactive substances method . In minced beef, added galangal extract improved oxidative stability . Galangal extract at higher concentrations of 0.05% and 0.10% (wt/wt) were also found to extend the shelf-life of minced beef . Addition of alpha-tocopherol (0.02%, wt/wt) to galangal extract (0.05%, wt/wt) were observed to increase the oxidative but not the microbial stability of minced beef during the storage of 7 days . Galangal extract may prove useful in inhibiting lipid oxidation and increasing microbial stability of minced meat. J Food Prot, 2000 Mar, 63(3), 376 - 80 Antimicrobial properties of pepsin-digested lactoferrin added to carrot juice and filtrates of carrot juice; Chantaysakorn P et al.; The objective of this study was to determine the antimicrobial activity of pepsin-digested lactoferrin added to carrot juice and filtrates prepared from carrot juice . Lactoferrin isolated from raw skim milk was digested by pepsin for 4 h at pH 3 . The digest of lactoferrin was lyophilized, and the antimicrobial activity of the digests was determined in peptone-yeast-glucose broth, carrot juice, permeate from carrot juice, and the dialysate of carrot juice permeate using Escherichia coli (American Type Culture Collection strain 35343) as the test organism . Growth of E . coli and the inhibitory effect of the peptide were greater in peptone-yeast-glucose broth at pH 7 than at pH 4 . The peptic digest of lactoferrin did not have antimicrobial properties in carrot juice at concentrations of less than 10 mg/ml of juice . Carrot juice was filtered through a membrane with a molecular weight rejection of 10,000 or 500 Da, and the permeate was dialyzed against distilled water . Growth of E . coli was delayed in the filtrate by 5 mg but not by 1 mg of the peptic digest of lactoferrin per ml of filtrate . Bacterial counts of the control and experimental samples were not significantly different after 24 h of incubation . The peptic digest of lactoferrin at a concentration of 5 mg of digest per ml of dialysate was bacteriostatic toward E . coli after 24 h of incubation at 23 degrees C . Dialysis of permeate caused a percentage reduction in cation concentration in the permeate ranging from 69.23% (Co) to 99.32% (Na) . The antimicrobial activity of lactoferrin added to carrot juice was probably inhibited by cations. Scand J Infect Dis, 2000, 32(1), 90 - 1 Hospital-acquired brevundimonas vesicularis septicaemia following open-heart surgery: case report and literature review; Gilad J et al.; Brevundimonas vesicularis (B . vesicularis) is a pseudomonad rarely encountered in human infection . A case of nosocomial septicaemia with this organism following open-heart surgery is presented, with a review of the literature . The isolate demonstrated resistance to ciprofloxacin and aztreonam, which has not yet been reported . Treatment with piperacillin/tazobactam resulted in full recovery . A review of the literature reveals that B . vesicularis is a virulent organism involved in serious infections such as central nervous system infection or bacteraemia, some of which are nosocomial . Meanwhile, empiric therapy for B . vesicularis infection should include a broad-spectrum antimicrobial agent until susceptibility results are known. Ann Trop Paediatr, 1999 Sep, 19(3), 237 - 43 Response to antimicrobial therapy in childhood bacterial meningitis in tropical Africa: report of a bi-centre experience in Nigeria, 1993-1998; Akpede GO et al.; Recent reports of a high prevalence of in-vitro resistance to chloramphenicol (CHL) and penicillin (PEN)/ampicillin (AMP) cause concern because of cost implications in using the newer cephalosporins (CEPH) to treat meningitis in resource-poor countries . However, the clinical significance of many of the observations is uncertain because of limited back-up by clinical data . We analysed the response in an open study of 161 patients with bacterial meningitis treated with CHL (n = 31), CHL plus PEN or AMP (n = 101), PEN or AMP (n = 14) and CEPH (n = 15) . No significant differences were observed in clinical course and outcome in the four treatment groups, other than a higher prevalence of seizures after 72 h of treatment and a higher prevalence of neurological sequelae in survivors in the CEPH and CHL groups . This may reflect the higher number of infants and greater frequencies of uncommon aetiological agents in the CHL and CEPH groups . It is concluded that response to initial chloramphenicol-based treatment regimens remains satisfactory and that there is as yet no compelling reason to switch to the cephalosporins as first-line therapy for bacterial meningitis in developing countries. J Am Dent Assoc, 2000 Mar, 131(3), 366 - 74 Antibiotic prophylaxis in dentistry: a review and practice recommendations; Tong DC et al.; BACKGROUND: The American Heart Association, or AHA, and the American Dental Association recently changed their recommended protocols for antibiotic prophylaxis against bacterial endocarditis . A new recommendation also has been issued by the ADA and the American Academy of Orthopaedic Surgeons, or AAOS, against routine antibiotic prophylaxis in patients with prosthetic joint replacements . These changes reflect increasing scientific evidence and professional experience in opposition to widespread use of antibiotic prophylaxis in these specific situations and others faced in dentistry . METHODS: The authors reviewed the medical and dental literature for scientific evidence regarding the use of antibiotics to prevent local and systemic infections associated with dental treatment . Situations commonly considered by dentists for potential use of prophylactic antibiotics were reviewed to determine current evidence with regard to use of antimicrobial agents . This included prevention of distant spread of oral organisms to susceptible sites elsewhere in the body and the reduction of local infections associated with oral procedures . RESULTS: There are relatively few situations in which antibiotic prophylaxis is indicated . Aside from the clearly defined instances of endocarditis and late prosthetic joint infections, there is no consensus among experts on the need for prophylaxis . There is wide variation in recommended protocols, but little scientific basis for the recommendations . The emerging trend seems to be to avoid the prophylactic use of antibiotics in conjunction with dental treatment unless there is a clear indication . CONCLUSIONS: Aside from the specific situations described, there is little or no scientific basis for the use of antibiotic prophylaxis in dentistry . The risk of inappropriate used of antibiotics and widespread antibiotic resistance appear to be far more important than any possible perceived benefit . CLINICAL IMPLICATIONS: Dentists are wise to use antibiotic prophylaxis in only those specific situations in which there is a valid scientific basis for it . Whenever possible, dentists should follow the standard protocols recommended by the ADA, AHA or AAOS. Phytomedicine, 2000 Jan, 6(6), 474 - 6 Arnebins and antimicrobial activities of Arnebia hispidissima DC . cell cultures; Jain SC et al.; The whole plant of Arnebia hispidissima DC . (Boraginaceae) is used for the treatment of tongue and throat ailments in Indian traditional medicine . The present paper deals with the plants phytochemical constituents, the arnebins, and antimicrobial activities of its root extract . The antimicrobial activities were tested against Gram-positive and Gram-negative bacteria and fungi . The crude hexane extract demonstrated a potent antimicrobial effect against bacteria and a mild effect against fungi . Likewise, the hexane extract of cell cultures of A . hispidissima also showed mild bioefficacy against the select microorganisms. J Nutr Biochem, 2000 Feb 1, 11(2), 94 - 102 Identification of lactoperoxidase in mature human milk; Shin K et al.; Myeloperoxidase (MPO) derived from milk leukocytes and lactoperoxidase (LPO) secreted from the mammary gland have been identified previously in human colostrum . These peroxidases are known to play host defensive roles through antimicrobial activity . The goals of this study were to measure the peroxidase activity in mature human milk and to characterize the enzyme responsible for the activity . As determined using 3,3',5,5'-tetramethylbenzidine as substrate, whey prepared from human milk samples obtained 1 and 5 months postpartum showed levels of peroxidase activity equivalent to 0.13 +/- 0.18 and 0.24 +/- 0.21 microg/mL bovine LPO (bLPO; n = 13), respectively . Whey from early milk was fractionated into two peaks of peroxidase activity by cation-exchange chromatography; the peroxidase in the first peak was sensitive to dapsone, which is an inhibitor of LPO, whereas the second peroxidase was not . Whey from mature milk showed only the first peak . Purified bLPO and MPO showed chromatographic behaviors that were similar to the first and second peaks, respectively . The dapsone-sensitive peroxidase from mature milk was further purified (952-fold from whey) by hydrophobic interaction chromatography . This preparation showed two bands with molecular masses of 80 and 90 kDa by polyacrylamide gel electrophoresis and immunoblotting using an antibody against bLPO . After deglycosylation, two distinct proteins with lower molecular weights were observed . Amino acid sequencing indicated that both of these proteins are LPO . These results provide evidence that LPO is present in mature human milk and that it is responsible for most of the peroxidase activity in mature milk. Am J Health Syst Pharm, 2000 Feb 15, 57(4), 339 - 45 Cost-effectiveness analysis of six strategies for cardiovascular surgery prophylaxis in patients labeled penicillin allergic; Phillips E et al.; The cost-effectiveness of different approaches to antimicrobial prophylaxis for cardiovascular surgery patients labeled penicillin allergic was studied . A decision-analytic model was used to examine the cost-effectiveness of six strategies for antimicrobial prophylaxis in cardiovascular surgery patients at a tertiary care hospital . The strategies consisted of (1) giving vancomycin to all patients labeled penicillin allergic, (2) giving cefazolin to all patients labeled penicillin allergic, (3) giving vancomycin to all patients with a history suggesting an immunoglobulin E (IgE)-mediated reaction to penicillin and cefazolin to patients without such a history, (4) administering a penicillin skin test to patients with a history suggesting an IgE-mediated reaction to penicillin and giving vancomycin to patients with positive results and cefazolin to all others, (5) skin testing all patients labeled penicillin allergic and giving vancomycin to those with positive results and cefazolin to those with negative results, regardless of history, and (6) skin testing all patients and giving vancomycin to those with positive results or a history suggesting an IgE-mediated reaction to penicillin and cefazolin to all others . Giving cefazolin to all patients labeled penicillin allergic was the least expensive strategy but was associated with the highest rate of both anaphylactic and non-life-threatening serious reactions . Selective use of vancomycin in patients with a history suggesting an IgE-mediated reaction to penicillin was associated with an added cost and a slightly lower rate of anaphylaxis . Although skin-testing strategies may decrease both non-life-threatening and anaphylactic reactions, the incremental cost was high . When vancomycin was given to all patients labeled penicillin allergic, the incremental cost was very high . A decision-analytic model indicated that selective use of vancomycin is more cost-effective than indiscriminate use of vancomycin for surgical prophylaxis in cardiovascular surgery patients labeled penicillin allergic. Surg Neurol, 2000 Feb, 53(2), 174 - 7 Isolated sphenoid sinus abscess: clinical and radiological failure in preoperative diagnosis . Case report and review of the literature; Oruckaptan HH et al.; BACKGROUND: Isolated sphenoid sinusitis and abscess formation is a rare entity, which can lead to misdiagnosed or improperly treated patients and an unfavorable outcome . Invasion of the skull base and cavernous sinus usually causes cranial nerve palsies, suggesting a neoplasm at the initial presentation . CASE DESCRIPTION: A case of isolated abscess in the sphenoid sinus is reported . The complete destruction of the clivus and its unexceptional radiological data, in addition to the absence of clinical and laboratory evidence of infection, led us to misdiagnose a possible clival chordoma during preoperative evaluation . The patient underwent an endonasal-transsphenoidal procedure for diagnosis and surgical removal . Surgical drainage and prolonged antimicrobial treatment resulted in complete clinical recovery . CONCLUSION: Its close proximity to vital structures and slender bony structures may allow the infection to disseminate, with serious neurological complications . On the other hand, the variable clinical presentations and radiological data usually cause delayed or missed diagnosis in these cases . This emphasizes the importance of documentation of this unusual entity and its radiological manifestations. Microbiol Immunol, 2000, 44(1), 9 - 15 Highly selective antibacterial activity of novel alkyl quinolone alkaloids from a Chinese herbal medicine, Gosyuyu (Wu-Chu-Yu), against Helicobacter pylori in vitro; Hamasaki N et al.; To elucidate the antibacterial activity of Gosyuyu, the crude extract from the fruit of Evodia rutaecarpa, a Chinese herbal medicine, has been fractionated chromatographically, and each fraction was assayed for antibacterial activity against Helicobacterpylori (H . pylori) in vitro . As the result, a single spot having marked antibacterial activity against H . pylori was obtained and the chemical structure was analyzed . The isolated compound was revealed to be a novel alkyl quinolone alkaloid based on the solubility, IR spectra, NMR analysis and mass spectrometric data after purification by TLC of silica . We compared the antimicrobial activity of this compound with that of other antimicrobial agents and examined susceptibility of various intestinal pathogens . As the result, the new quinolone compounds obtained from Gosyuyu extracts were found to be a mixture of two quinolone alkaloids, 1-methyl-2-{(Z)-8-tridecenyl}-4-(1H)-quinolone and 1-methyl-2-{(Z)-7-tridecenyl}-4-(1H)-quinolone (MW: 339), reported previously . The minimum inhibitory concentration (MIC) of these compounds against reference strains and clinically isolated H . pylori strains were less than 0.05 microg/ml, which was similar to the MIC of amoxicillin and clarithromycin that are used worldwide for the eradication of H . pylori, clinically . Furthermore, it was noted that the antimicrobial activity of these compounds was highly selective against H . pylori and almost non-active against other intestinal pathogens . The above results showed that these alkyl methyl quinolone (AM quinolones) alkaloids were useful for the eradication of H . pylori without affecting other intestinal flora. Pharmacotherapy, 2000 Feb, 20(2), 199 - 205 Increased therapeutic failure for cephalexin versus comparator antibiotics in the treatment of uncomplicated outpatient cellulitis; Madaras-Kelly KJ et al.; We reviewed records of outpatients to determine the therapeutic failure rate of cephalexin in treating uncomplicated cellulitis . Therapeutic failure was defined as an increase in antibiotic dosage, prescription renewal, or addition or substitution of another antibiotic . Demographics, physical characteristics, risk factors, intervention, and outcome data were collected . Twenty-seven percent of patients failed therapy with an oral antibiotic . The failure rate for cephalexin was 40% versus 20% for comparator antibiotics (p=0.02, odds ratio {OR} 2.62, 95% confidence interval {CI} 1.18-5.75) . We identified no statistically significant variables related to cephalexin failure . Concomitant acid suppressive therapy was administered with cephalexin in 42% of failures and 20% of nonfailures (p=0.11, OR 2.78, 95% CI 0.77-9.87) . These data suggest that cephalexin's efficacy was less than that of other antimicrobials in treating cellulitis, possibly related to concurrent acid suppression. Pharmacotherapy, 2000 Feb, 20(2), 166 - 81 Aerosolized antimicrobial therapy in acutely ill patients; Wood GC et al.; Recent data are sparking renewed interest in therapy with aerosolized antimicrobials in critically ill patients as well as other populations such as those with neutropenia, human immunodeficiency virus infection, and cystic fibrosis . Pneumonia is a common complication in these patients and is associated with substantial morbidity and increased mortality . Clinical trials evaluated aerosolized antimicrobials for the prevention and treatment of pneumonia in hospitalized patients . In addition, factors that affect the pulmonary deposition of aerosolized drugs in mechanically ventilated patients were identified. Arch Pediatr Adolesc Med, 2000 Mar, 154(3), 267 - 70 Palatability of oral antibiotics among children in an urban primary care center; Angelilli ML et al.; OBJECTIVE: To evaluate the palatability of antimicrobial agents effective against beta-lactamase-producing bacteria in American children . DESIGN: In a taste test of 4 antimicrobial agents, azithromycin (cherry flavored), cefprozil (bubble gum flavored), cefixime (strawberry flavored), and amoxicillin-clavulanic acid (banana flavored) were compared . SETTING: An urban inner-city primary care clinic . SUBJECTS: A volunteer sample of 30 healthy children (aged 5-8 years) . INTERVENTION: Palatability was determined using a single-blind taste test of 4 flavored antimicrobial agents . The 4 antimicrobial agents used were azithromycin, cefprozil, cefixime, and amoxicillin-clavulanic acid . MAIN OUTCOME MEASURES: After each antimicrobial test dose, subjects rated the taste on a 10-cm visual analog scale incorporating a facial hedonic scale . Preference assessments for the best-tasting and worst-tasting agent were also conducted . RESULTS: Of the 20 children who expressed a preference, significantly more children (9 {45%}, P<.05) selected the cefixime preparation as the best-tasting formulation compared with the other preparations . The cefixime preparation was also significantly the least likely to be selected as the worst-tasting preparation (2 {10%}, P<.05) . There were no significant differences between the other 3 preparations with respect to being selected as either the best or worst tasting . The mean (+/- SD) visual analog scale score for cefixime was highest (8.53 {2.49}) compared with the scores for azithromycin (6.78 {3.45}), cefprozil (6.26 {4.04}), and amoxicillin-clavulanic acid (6.24 {4.01}) . CONCLUSION: The cefixime preparation was most commonly rated as best tasting by children. Implant Dent, 1999, 8(3), 247 - 54 Treatment of peri-implantitis: longitudinal clinical and microbiological findings--a case report; Muller E et al.; Failing implants can be successfully treated by surgical procedures that use either bone fillers or membranes combined with an antimicrobial treatment . In this report, we present a case of failing implants with the corresponding treatment and results of 8 years of follow-up. Therapie, 1999 Nov-Dec, 54(6), 731 - 3 Antibacterial and antifungal activities of Cistus incanus and C . monspeliensis leaf extracts; Bouamama H et al.; In this study, the antimicrobial activity of leaf extracts obtained from two species of genus Cistus L . was examined in vitro against five strains of bacteria and five strains of fungi . The species studied are Cistus villosus L . = incanus and Cistus monspeliensis L . All extracts showed inhibitory activity against microorganisms . These results encourage us towards further biological investigation. Arch Oral Biol, 2000 Apr, 45(4), 257 - 65 The effect of minocycline on the metabolism of androgens by human oral periosteal fibroblasts and its inhibition by finasteride; Soory M et al.; The antimicrobial minocycline has matrix-stimulatory effects on connective tissue and bone . The aim here was to study the effect of minocycline on 5alpha reduction of androgen substrates to 5alpha-dihydrotestosterone (DHT) in periosteal fibroblasts and the influence of the antiandrogen finasteride on this conversion . Confluent cultures of periosteal fibroblasts established from oral periosteum isolated from the bone surface were incubated in duplicate in multiwell dishes with two androgen substrates, {(14)C}-testosterone/{(14)C}-4-androstenedione, in the presence or absence of serial concentrations of minocycline or the antiandrogen finasteride or the two in combination for 24 h . The metabolites formed were solvent-extracted with ethyl acetate, separated by thin-layer chromatography and quantified using a radioisotope scanner . Both androgen substrates were metabolized to DHT and 4-androstenedione or testosterone . Minocycline stimulated the synthesis of DHT from these substrates by 75-83% at 20-30 microg/ml (n=4; p<0.01) . Finasteride inhibited the 5alpha-reductase activity of these substrates by 3-5-fold at 1 microg/ml and 40-80% at 0.01 and 0.1 microg/ml (n=4; p<0.01), with little change in 17beta-hydroxysteroid dehydrogenase activity . Minocycline and finasteride in combination showed an intermediate response with one substrate . As finasteride inhibits the type 2, 5alpha-reductase isoenzyme associated with anabolic functions, these findings demonstrate target-tissue androgen metabolic activity in periosteal fibroblasts at baseline and in response to minocycline . This has implications for the reparatory potential of the diseased periodontium during adjunctive treatment with minocycline. Vet Clin North Am Food Anim Pract, 2000 Mar, 16(1), 135 - 61 Diarrhea in growing-finishing swine; Wills RW; Regardless of the etiology of an enteric disease in nursery age to finisher swine, making a prompt and accurate diagnosis is crucial . Eliciting a complete history, assessing clinical signs and pathology, and selecting and interpreting laboratory tests are essential components in achieving this . Early detection and diagnosis of enteric disease is particularly critical in the nursery through finisher phase because of economic impacts . Recurrent topics when discussing control and prevention of enteric diseases are reducing stress and improving pig comfort and reducing or eliminating exposure through sanitation and biosecurity . These are not new concepts; in fact, prior to the advent of antimicrobials, they were the mainstay of treatment of enteric diseases . With concern over the use of antimicrobials in food animal production increasing, exploiting disease ecology to control enteric diseases is increasing in importance . New vaccines and bacterins for postweaning swine enteric diseases are needed tools to exploit the pig's immune system . Recent advances in diagnostic capabilities allow an increase in understanding and exploitation of disease ecology. J Hosp Infect, 2000 Mar, 44(3), 227 - 39 The population impact of MRSA in a country: the national survey of MRSA in Wales, 1997; Morgan M et al.; Continuous data collection on all new isolates of MRSA via CoSurv has taken place in Wales since January 1996 . In order to audit this data collection, and to address some of the issues that it does not include, a survey of MRSA was carried out . Questionnaires were completed by infection control teams . Rates were calculated using hospital throughput denominators . Results from the one-day prevalence survey, the two-week incidence survey, and the follow-up survey carried out on new MRSA patients identified in the incidence survey, are presented . Results were found to be broadly similar to those collected via routine surveillance . MRSA was found frequently and disproportionately in the elderly, with higher rates in male than female patients . The highest incidence of total and invasive MRSA was in males aged 75 and over (total: 12.5/1000 finished consultant episodes; invasive: 2.8/1000) . Although there was a large community reservoir of MRSA, most appeared to have been acquired in hospital, since most patients had a history of hospitalization, often with multiple hospital admissions . Community-based isolates from cases with no hospital history tended to have been from ulcers . Prevalence and incidence of MRSA was relatively low compared with hospital throughput (mean prevalence: 2.4/100 occupied beds; mean incidence: 3.6/1000 finished consultant episodes), there was also quite large variation between sites, even when screening samples were removed . Patients with MRSA had strikingly long stays before isolation of the organism (prevalence survey: 39 days; incidence survey: 31 days) and highest incidence occurred in elderly care wards . The outcome survey showed that approximately half of the patients were treated with some type of antimicrobial therapy for MRSA . Decontamination therapy was associated with clearance of MRSA only when controlling for sex of the patient . The majority of patients were discharged still with MRSA, mostly to their own homes . The survey emphasizes the need to continue surveillance to detect any changes, to allow guidelines based on evidence to be developed and to monitor the effectiveness of such guidelines . Blood, 2000 Mar 15, 95(6), 2150 - 6 Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease; Roesler J et al.; Chronic granulomatous disease (CGD) is an inherited disease caused by defects in the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase of phagocytes . Genetic lesions in any of 4 components of this antimicrobial enzyme have been detected . Family-specific mutations are found in 3 of 4 forms of CGD due to deficiencies of the gp91-phox, p22-phox, and p67-phox genes . In p47-phox-deficient CGD (autosomal recessive form A47 degrees ) patients, a GT deletion (triangle upGT) at the beginning of exon 2 of the p47-phox gene has been reported in 19 of 20 alleles . This GT deletion is also characteristic for the recently identified p47-phox pseudogenes . To explore a possible link between these findings, a sequence analysis of 28 unrelated, racially diverse A47 degrees CGD patients and 37 healthy individuals was performed . The GT deletion in exon 2 was present on all alleles in 25 patients . Only 3 patients but all healthy individuals contained the GTGT and triangle upGT sequences . A total of 22 patients carried additional pseudogene-specific intronic sequences on all alleles, either only in intron 1 or in intron 1 and intron 2, which lead to different types of chimeric DNA strands . It is concluded that recombination events between the p47-phox gene and its highly homologous pseudogenes result in the incorporation of triangle upGT into the p47-phox gene, thereby leading to the high frequency of GT deletion in A47 degrees CGD patients . (Blood . 2000;95:2150-2156) J Immunol, 2000 Mar 15, 164(6), 3264 - 73 Role of CCAAT/enhancer-binding protein site in transcription of human neutrophil peptide-1 and -3 defensin genes; Tsutsumi-Ishii Y et al.; The human neutrophil defensins (human neutrophil peptides (HNPs)), major components of azurophilic granules, contribute to innate and acquired host immunities through their potent antimicrobial activities and ability to activate T cells . Despite being encoded by nearly identical genes, HNP-1 is more abundant in the granules than HNP-3 . We investigated the regulation of HNP-1 and HNP-3 expression at the transcriptional level using a promyelocytic HL-60 cell line . Luciferase analysis showed that transcriptional levels of HNP-1 and HNP-3 promoters were equivalent and that an approximately 200-bp region identical between promoters was sufficient for transcriptional activity . Furthermore, overlapping CCAAT/enhancer-binding protein (C/EBP) and c-Myb sites in the region were found to be required for efficient transcription . Gel mobility shift assay demonstrated that C/EBPalpha predominantly bound to the C/EBP/c-Myb sites using HL-60 nuclear extracts . No specific binding to C/EBP/c-Myb sites was observed in nuclear extracts from mature neutrophils, which expressed neither C/EBPalpha protein nor HNP mRNAs . Taken together, these findings suggest that the difference in the amounts of HNP-1 and HNP-3 peptides in neutrophils is caused by posttranscriptional regulation and that C/EBPalpha plays an important role in the transcription of HNP genes in immature myeloid cells. Eur J Clin Microbiol Infect Dis, 2000 Jan, 19(1), 27 - 32 New colorimetric microdilution method for in vitro susceptibility testing of Borrelia burgdorferi against antimicrobial substances; Hunfeld KP et al.; A newly developed colorimetric microdilution method was used to analyze the activity of 12 antimicrobial agents against nine Borrelia burgdorferi isolates, including all three genospecies pathogenic for humans . In addition, in vitro antimicrobial resistance patterns of Borrelia valaisiana and Borrelia bissettii tick isolates were investigated . The applied test system is based upon color changes that occur in the presence of phenol red and result from the accumulation of nonvolatile acid produced by actively metabolizing spirochetes . After 72 h of incubation, minimal inhibitory concentrations (MICs) were determined from the decrease of absorbance by software-assisted calculation of growth curves . MIC values were lowest for azlocillin (MIC, < or = 0.125 microg/ml), ceftriaxone (MIC range, < or = 0.015-0.06 microg/ ml), and azithromycin (MIC range, < or = 0.015-0.06 microg/ml) . Whereas tobramycin (MIC range, 8-64 microg/ml) exhibited little activity, spectinomycin (MIC range, 0.25-2 microg/ml) showed in vitro antimicrobial activity against Borrelia burgdorferi . The MICs of penicillin G for Borrelia afzelii isolates were ten times higher than those for Borrelia burgdorferi, Borrelia valaisiana, and Borrelia bissettii isolates (P<0.05) and 100 times higher than those for isolates belonging to the genospecies Borrelia garinii (P < 0.05) . Further significant differences with respect to the MIC values of the other antimicrobial agents tested were not noted . The colorimetric microdilution method offered the advantages of reliability, reproducibility, and convenience and could handle large numbers of isolates and antibiotics. Recenti Prog Med, 2000 Jan, 91(1), 12 - 5 {Efficacy and safety of clarithromycin in the treatment of community-acquired pneumonia}; Parola D et al.; Community-acquired pneumonia (CAP) is a serious disease frequently treated empirically, which required the selection of an antibiotic that covers all common pathogens and achieves good pulmonary concentrations . The availability of intravenous (i.v.) formulations may also be helpful, permitting i.v./p.o . sequential therapy . From January 1992 to December 1997 we treated 290 CAP patients with clarithromycin (CL) 500 mg BID, first given i.v . in 250 or 500 ml of saline solution and then switched after 4-5 days to the same dosage given p.o . Of these 290 patients 163 were males (98 smokers) and 127 were females (41 smokers); 87 were over 65 years old and 203 had concomitant diseases (mainly cardiovascular), 172 patients were admitted after unsuccessful therapy (122 cephalosporins and 48 penicillins) . Diagnosis was made based on clinical and radiological findings, therapy was initiated prior to microbiological diagnosis . Clinical and radiological improvement was achieved by 261/290 patients (90%) within 10-15 days . Mild adverse events occurred in 11 patients . This results indicate that CL is effective and safe: its antimicrobial spectrum and pharmacokinetic profile, the possibility of i.v./p.o . sequential administration, make it an ideal antibiotic for the treatment of CAP. Zentralbl Bakteriol, 2000 Jan, 289(8), 869 - 78 Isolation of Mobiluncus species from the human vagina; Gatti M; We report the results of a study concerning the characteristics of 52 strains of Mobiluncus spp . isolated from 982 vaginal secretions from patients with suspected bacterial vaginosis . 158 of these women presented the features of this bacterial infection . Of the strains isolated, 39 belonged to the species Mobiluncus curtisii, (25 of these which to M . curtisii subsp . curtisii and 14, to M . curtisii subsp . holmesii), and 13, to Mobiluncus mulieris . The vaginal isolates of Mobiluncus spp . were identified by comparing their biochemical profiles with those of the type strains M . curtisii subsp . holmesii (ATCC 35,242), M . curtisii subsp . curtisii (ATCC 35,241) and M . mulieris (ATCC 35,243) . All strains of M . mulieris proved to be sensitive to the antimicrobial agents assayed, while strains of M . curtisii were seen to be resistant only to metronidazole. Chem Pharm Bull (Tokyo), 2000 Jan, 48(1), 160 - 2 Reaction of 3-acetonyl-5-cyano-1,2,4-thiadiazole with phenylhydrazine hydrochlorides: indolization and phenylpyrazolation; Iwakawa T et al.; Treatment of 3-acetonyl-5-cyano-1,2,4-thiadiazole (1) with 4-methyl or 4-methoxyphenylhydrazine hydrochloride provided 5-cyano-3-(2,5-dimethylindol-3-yl)-1,2,4-thiadiazole (2) or 5-cyano-3-(5-methoxy-2-methylindol-3-yl)-1,2,4-thiadiazole (3) as the sole product, respectively . In contrast, treatment of 1 with phenylhydrazine hydrochloride resulted in the formation of 5-cyano-3-(2-methylindol-3-yl)-1,2,4-thiadiazole (4) and the unexpected 5-cyano-3-(3,5-dimethyl-1-phenylpyrazol-4-yl)-1,2,4-thiadiazole (5) . In a similar manner, when 1 was treated with 4-chlorophenylhydrazine hydrochloride, indolization was suppressed by phenylpyrazolation giving rise to 5-cyano-3-(5-chloro-2-methylindol-3-yl)-1,2,4-thiadiazole (6) and 5-cyano-3-{1-(4-chlorophenyl)-3,5-dimethylpyrazol-4-yl}-1,2,4-thia diazole (7) . The reaction mechanism is discussed . Compounds 4, 5 and 6 exhibited weak antimicrobial activity against Helicobacter pylori. Biochim Biophys Acta, 2000 Mar 15, 1464(1), 135 - 41 Squalamine is not a proton ionophore; Selinsky BS et al.; Squalamine, an aminosterol antibiotic isolated from the dogfish shark, creates relatively large defects in phospholipid bilayers, allowing the unrestricted translocation of small molecules across these compromised membranes (B.S . Selinsky, Z . Zhou, K.G . Fotjik, S . R . Jones, N.R . Dollahon, A.E . Shinnar, Biochim . Biophys . Acta 1370 (1998) 218-234) . However, an aminosterol structurally similar to squalamine was found to act as a proton ionophore in anionic phospholipid vesicles . In contrast with squalamine, gross membrane disruption was not observed with this synthetic analog (G . Deng, T . Dewa, S.L . Regen, J . Am . Chem . Soc . 118 (1996) 8975-8976) . In this report, the ionophoric activity of squalamine was tested in anionic and zwitterionic phospholipid vesicles . No ionophoric activity was observed for squalamine in vesicles comprised of phosphatidylglycerol (PG), phosphatidylcholine (PC), or a mixture of the two lipids . Experiments using radiolabeled squalamine indicated that all of the squalamine added to PG vesicles remained with the vesicles, while approximately one-half of the squalamine added to PC vesicles was incorporated . We have synthesized the aminosterol analog of squalamine possessing ionophoric activity, and its ionophoric activity in PG vesicles was confirmed . The synthetic compound possessed no measurable lytic activity when added to preformed phospholipid vesicles . As both compounds possess significant antimicrobial activity, these results suggest that either multiple mechanisms for the antimicrobial activity of aminosterols exist, depending upon the aminosterol structure, or possibly an unrelated common mechanism for antimicrobial activity remains to be discovered. Int J Parasitol, 2000 Feb, 30(2), 149 - 55 Measurement of the efficacy of vaccines and antimicrobial therapy against infection with Toxoplasma gondii; Kirisits MJ et al.; To facilitate studies of vaccines and antimicrobial agents effective against Toxoplasma gondii infection, an assay system was developed to semi-quantitate parasitaemia using PCR amplification of T . gondii DNA obtained from the blood of mice infected with the parasite . A competitive internal standard DNA fragment of the B1 gene of T . gondii was generated and used in PCR so that the amplified product could be semi-quantitated and false negative results could be avoided . The PCR assay system was used to analyse the levels of parasitaemia in immunised and antimicrobial agent treated mice at various times after infection with T . gondii . The results of these studies indicate that this highly sensitive detection method is a rapid and reliable procedure that can be employed to assess the abilities of vaccines or antimicrobial agents to provide protection early following T . gondii infection. Rev Med Suisse Romande, 2000 Jan, 120(1), 59 - 64 {Is there a role for infectious disease specialists in private practice?}; Erard P; For the last 20 years infectious diseases have gained increasing importance for hospital medicine . As a specialty, infectious diseases have been recognized only recently by the Swiss medical association . However, the precise role of infectious disease specialist operating in private practice remain to be defined . The medical community faces many challenges for which infectious disease specialist must provide answers . Knowledge in microbiology has progressed enormously and many very sophisticated and, partly, expensive diagnostic techniques are widely available . New treatment options are introduced while numerous microbial species demonstrate increasing resistance to antimicrobial agents . The intervention of infectious disease specialist could thus contribute to optimize treatment and limit the use of economic resources . Infectious disease specialist in private practice are also facing new activities such as parenteral outpatient treatment for severe infections and HIV infection, which clearly require a specialized professional approach . Infectious disease specialist in private practice will need great care to find a responsible equilibrium between clinical consultation and telephone consultation. J Clin Periodontol, 2000 Feb, 27(2), 79 - 86 Antimicrobial resistance in the subgingival microflora in patients with adult periodontitis . A comparison between The Netherlands and Spain; van Winkelhoff AJ et al.; BACKGROUND: The widespread use of antibiotics for prophylaxis and treatment of bacterial infections has lead to the emergence of resistant human pathogens . Great differences have been documented between European countries in the use of systemic antibiotics . In parallel, significant differences in levels of resistant pathogens have been documented . AIM: To investigate whether differences in antibiotic use influence the level of antimicrobial resistance of the subgingival microflora of untreated patients with adult periodontitis in The Netherlands and Spain . METHOD: Blood agar plates containing breakpoint concentrations of penicillin, amoxicillin, amoxicillin and clavunalate, metronidazole, erythromycin, azithromycin, clindamycin and tetracycline were used to determine the proportion of bacteria from the subgingival plaque that was resistant to these antibiotics . In the Spanish patients, statistically significant higher mean levels of resistance were found for penicillin, amoxicillin, metronidazole, clindamycin and tetracycline . The mean number of different bacterial species growing on the selective plates was higher in the Spanish patients, as was the % of resistant strains of most periodontal pathogens . A striking difference was observed in the frequency of occurrence of tetracycline-resistant periodontal pathogens . In Spain, 5 patients had > or =3 tetracycline resistant periodontal pathogens, whereas this was not observed in any of the Dutch patients . CONCLUSIONS: The widespread use of antibiotics in Spain is reflected in the level of resistance of the subgingival microflora of adult patients with periodontitis. Oral Dis, 2000 Mar, 6(2), 124 - 31 Effects of 0.12% chlorhexidine gluconate on experimental gingivitis in non-human primates: clinical and microbiological alterations; Cappelli D et al.; OBJECTIVE: This study examined the efficacy of 0.12% chlorhexidine gluconate (Peridex) to reduce gingival inflammation in the absence of mechanical hygiene and its effect on the oral microbial ecology in a non-human primate (NhP) model of gingivitis . DESIGN: Twelve NhP were stratified based on existing inflammation into two groups of six NhP per group . Oral hygiene was performed on both groups so as to reach a level of gingival health (BOP < or = 0.3) at the conclusion of the hygiene phase . One group received 30 ml of 0.12% chlorhexidine gluconate twice daily 7 days/week, and a second group received 30 ml of placebo (distilled water colored to match the active) using the same regimen for 10 weeks . MEASUREMENT OUTCOMES: Clinical parameters including plaque (PLI), pocket depth (PD), attachment level (AL), and bleeding on probing (BOP) were evaluated at 2-week intervals . Subgingival plaque samples were collected by paper point at 2-week intervals and cultured for predominant cultivable bacteria . RESULTS: By week 2, there was a difference in BOP between the groups, which reached statistical significance by week 4 . This difference in BOP was maintained throughout the course of the study . Chlorhexidine gluconate (0.12%) had no significant effect on PLI, PD, or AL; although PD was greater in the placebo group after week 2 and throughout the study . Microbiologically, at week 4, the treatment group had a reduction in total bacterial counts, as well as Gram positive bacteria, and total black pigmented bacteria, compared to the placebo group . However, only the differences in Actinomyces spp . reached significance . Interestingly, when both groups received only one treatment/day on the weekends (i.e., day 6 and 7), an associated loss of statistically significant differences between the two groups was observed . Additional experiments dosing the non-human primates once daily, 5 days/week yielded no significant differences in clinical parameters, including bleeding, when compared with the placebo group . CONCLUSION: Non-human primates provided a model system of gingivitis for testing antimicrobial agent effects on the subgingival ecology and accompanying inflammatory responses . Chlorhexidine gluconate (0.12%), even in the absence of mechanical hygiene, was effective in inhibiting clinical signs of inflammation, associated with alterations in the subgingival microbial ecology, most notably Actinomyces spp. J Antimicrob Chemother, 2000 Mar, 45(3), 395 - 400 Non-hospital consumption of antibiotics in Spain: 1987-1997; Bremon AR et al.; Spain has one of the highest incidences of bacterial resistance to antimicrobials, possibly linked to drug consumption patterns . Using Ministry of Health and Consumer Affairs records, data were obtained on non-hospital sales of antibiotics for the period 1987-1997, and equivalents calculated in weight of active drug ingredient and defined daily doses per 1000 population per day (DDD/1000/day) . The number of packages sold declined from 75 million in 1987 to 55 million in 1997 . None the less, there was a gradual yet steady rise in consumption in tonnage terms (249 to 275 tonnes) . Furthermore, in terms of DDD/1000/day, consumption rose sharply until 1995 and then held steady at 21 DDD/1000/day, a level comparable to the mean for other developed countries . Penicillins were the group to register the highest consumption in Spain, followed-in the latter years of the study-by macrolides, cephalosporins and quinolones . The marked rise in these latter three groups was noteworthy . Despite the decrease in the number of packages sold, antibiotic consumption in Spain has risen . This consumption pattern is different from that of other European countries and might serve to explain differences in the generation of resistance. J Antimicrob Chemother, 2000 Mar, 45(3), 387 - 94 Use of a treatment protocol in the management of community-acquired lower respiratory tract infection; Al-Eidan FA et al.; The aim of the present study was to examine the impact of an antimicrobial prescribing protocol on clinical and economic outcome measures in hospitalized patients with community-acquired lower respiratory tract infection (LRTI) . The study was performed as a prospective controlled clinical trial within the medical wards at Antrim Area Hospital, Northern Ireland . Data were collected on all hospitalized adult patients with a primary diagnosis of LRTI during the period December 1994 to February 1995 (normal hospital practice; control group; n = 112) . After an LRTI management protocol (medical, microbiological and pharmacy staff) had been developed, all hospitalized adult patients with a primary diagnosis of LRTI over the period December 1995 to February 1996 formed the intervention group (treated according to the protocol; n = 115) . The results showed a statistically significant impact of the protocol in terms of clinical and economic outcome measures . Patients treated using the algorithmic prescribing protocol had significant reductions in length of hospital stay (geometric mean 4.5 versus 9.2 days), iv drug administration (34.8% versus 61.6%), duration of iv therapy (geometric mean 2.1 versus 5.7 days) and treatment failures (7.8% versus 31.3%) . Healthcare costs were also significantly reduced . The use of the protocol was a major factor in streamlining the prescribing of antimicrobial therapy for community-acquired LRTI and led to more cost-effective patient management. Vet Microbiol, 2000 Feb, 71(3-4), 193 - 200 Antibiotic susceptibility of canine Bordetella bronchiseptica isolates; Speakman AJ et al.; The antimicrobial sensitivities of 78 recent (1995-1998) canine isolates of Bordetella bronchiseptica from 13 separate sources were determined . Minimum inhibitory concentrations were assessed using the E-test method or by agar dilution . All 78 isolates were sensitive to tetracycline, doxycycline, enrofloxacin, and amoxycillin/clavulanic acid; the majority were sensitive to ampicillin (63/78; 81%), trimethoprim (57/78; 73%), and sulphadiazine (63/78; 81%) . Plasmids were detected in 14 out of the 24 isolates tested . There was no correlation between the presence of plasmids and antibiotic resistance, but there was some correlation between the presence of plasmids and the origin of the isolates . Three sizes of plasmid were found: 20, 14, and 5.5 kb . Eight of the isolates contained all three plasmids, the remainder one or two, Thirteen isolates demonstrated beta-haemolysis, of which six produced a soluble haemolysin . Except for one isolate, haemolysin production correlated with plasmid carriage . Pulsed-field gel electrophoresis showed that all except one isolate could be grouped in the same genotype . Within this genotype isolates could be divided into three subtypes, generally corresponding to their place of origin. Rev Esp Cardiol, 2000 Jan, 53(1), 139 - 41 {Employment of St . Jude "silzone" valve in the surgical treatment of early prosthetic valve endocarditis: a preliminary case report and review of the literature}; Garcia Fuster R et al.; Prosthetic valve endocarditis remains as one of the most life-threatening complication of valve replacement surgery . Homografts are the valve of choice with a lower early risk of endocarditis than other valve substitutes, however they are not always available . Recently a new prosthesis has been introduced with a silver-coated sewing cuff (St . Jude Medical with Silzone coating) . Silver is an antimicrobial agent that has been proven to reduce bacterial colonization . We present the case of a 48-year-old man with an early prosthetic valve endocarditis which affected an aortic stentless prosthesis . He was successfully treated with a silver-coated prosthesis . Indications for surgery and the use of this prosthesis as a valuable option in this disease entity are discussed . Although the present patient is an isolated case, the interest of this article is the encouraging result obtained with this new prosthesis for this serious complication . Moreover, the clinical experience is reduced with only a few reports in the literature. J Cell Physiol, 2000 Apr, 183(1), 91 - 9 Adaptive responses of human monocytes infected by bordetella pertussis: the role of adenylate cyclase hemolysin; Njamkepo E et al.; The activation/adaptive responses of human monocytes exposed to Bordetella pertussis parental or mutant strains were evaluated and correlated to the expression of two bacterial toxins: adenylate cyclase-hemolysin and pertussis toxin . The marked rise in intracellular cyclic adenosine monophosphate (cAMP) observed in monocytes infected by B . pertussis parental strain, inversely correlated with (1) the production of tumor necrosis factor alpha; (2) the release of superoxide anion; and (3) the expression of the 72-kDa heat shock/stress protein, Hsp70 . Experiments performed with mutants deficient in adenylate cyclase-hemolysin or with purified bacterial toxins confirmed the key role of adenylate cyclase-hemolysin in the control of monocytes' response to infection by B . pertussis . This bacterial strategy primarily involves evasion from antimicrobial defenses and, eventually, the sacrifice of the host cell . J Am Podiatr Med Assoc, 2000 Feb, 90(2), 93 - 7 Wound-care resources on the Internet; Fikar CR et al.; The Internet offers many resources in the area of wound and ulcer care that are of potential interest to podiatric physicians and students . This article provides an overview of World Wide Web sites that contain factual information, management guidelines, and illustrations pertaining to various aspects of wound and ulcer care . Web sites that emphasize preventive care are also reviewed . Because the prudent use of antimicrobial therapy is an important part of wound care, a few sites that offer antibiotic information are described. Anticancer Res, 1999 Nov-Dec, 19(6B), 5075 - 8 Plasmid elimination and immunomodulation by 3-benzazepines in vitro; Motohashi N et al.; For studying the mechanisms of biological activity on 3-benzazepines, antimicrobial effect, F'lac plasmid elimination activity (a plasmid curing effect on F'lac plasmid) and antibody-dependent cellular cytotoxicity (ADCC) test were performed . A weak antiplasmid effect was found at sub-inhibitory concentrations . A combination of {KF4} with verapamil {2} did not alter the ineffectivity, however, {KF4} could inhibit the antiplasmid effect of promethazine, as compared to the control (promethazine alone) plasmid curing effect . A competition between promethazine and {KF4} might exist in plasmid elimination effect . ADCC activity of human leukocytes was enhanced by KF1, KF2, KF3, DA and NE at 1.0 microgram/mL concentrations . The majority of 3-benzazepines {KS02, KM57, KN50, KE04, KI10, KP80} was ineffective for plasmid curing, however, inhibited the ADCC reaction, but they did not show a real dose-dependent effect. J Pharm Biomed Anal, 1999 Jul, 20(3), 459 - 69 Macrolide and ketolide antibiotic separation by reversed phase high performance liquid chromatography; Lingerfelt B et al.; Twenty different macrolide and ketolide antibiotics were analyzed by reversed phase high performance liquid chromatography on an ODS-2 cartridge column . Each of these compounds was uniquely separated and purified by varying the flow rate . Retention times of the individual drugs were proportional to the flow rate of the mobile phase . Recovery of antimicrobial activity for most of the drugs was greater than 90% based on a microbiological assay of material recovered from the column . Retention times were related to structural differences between these antimicrobial agents. Parassitologia, 1999 Sep, 41(1-3), 177 - 80 Host-parasite intimacy: how do mosquito defense reactions affect Plasmodium sporogonic development? Brey PT. Here are a few sundry reflections and questions stimulated by the talks and discussions in session 3 of the Malariology Centenary Conference 1998 on the 'intimacy' that has been established between Plasmodium and Anopheles . The degree of 'intimacy' achieved in a vectorial system seems to correlate to the difficulties incurred when one attempts to interrupt parasite development in the insect host . The main questions addressed in this essay are as follows: Are antimicrobial peptides the most efficient effector molecules to be used to block sporogonic development of malaria parasites? Are the mosquito defense reactions elicited by Plasmodium invasion deleterious, advantageous or neutral to parasite development? The purpose in asking these questions is to put in perspective the direction of research in this area and to generate new ideas. Infection, 2000 Jan, 28(1), 60 - 4 Linezolid, critical characteristics Hamel JC, Stapert D, Moerman JK, Ford CW. In spite of a constantly expanding information base with the oxazolidinones generally and linezolid specifically, we have elected here to focus on the key characteristics of linezolid . Linezolid is the first member of a new class of antimicrobial agents, the oxazolidinones, to be tested in humans in Phase I, Phase II and Phase III clinical trials . The oxazolidinones have a novel mechanism of action in that they inhibit initiation complex formation in bacterial protein synthesis and, consistent with a novel mechanism of action, they do not exhibit cross-resistance with existing antibacterial agents . Importantly, resistance development as measured in the laboratory occurs very slowly, there is no evidence of rapid resistance development . The spectrum of oxazolidinone activity is principally gram-positive and in vitro studies demonstrate that linezolid is equivalent to vancomycin in vitro . Linezolid is orally as well as intravenously active and orally administered linezolid is as efficacious in mouse models of bacterial disease as is subcutanously administered vancomycin against appropriate pathogens . The exceptional oral behavior of linezolid in mouse models is readily explained by the observation that oral linezolid is 100% bioavilable and that administration of 400- and 600-mg doses of linezolid in humans results in blood level curves which predict that linezolid will be very well suited for bid dosing . Additionally, the blood level concentrations are in significant and very comfortable excess of the MIC90 concentrations for the important gram-positive pathogens for the bulk of the dosing interval. J Heart Valve Dis, 2000 Jan, 9(1), 123 - 9; discussion 129-30 First clinical experience with a mechanical valve with silver coating; Brutel de la Riviere A et al.; BACKGROUND AND AIM OF THE STUDY: The interface between the annulus and sewing cuff is the infectious center of prosthetic valve endocarditis (PVE) . To decrease the incidence of PVE, the sewing cuff of the St . Jude Medical (SJM) mechanical heart valve was permanently coated with elemental silver (Silzone coating) . In vitro data have supported the antimicrobial efficacy of this coating . METHODS: To study any adverse effects of the silver coating in humans, serum silver levels were determined (by graphite furnace atomic absorption spectrometry) before (baseline) and at five intervals after operation: day 1, day 3, discharge, one month, and two months . Between January and August 1997, 38 patients (71% ma