Antimicrobials

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% males) underwent surgical implant of a SJM Masters Series valve with Silzone coating for the aortic valve (n = 29), mitral valve (n = 6), or both valves (n = 3) . Five patients (13%) underwent concomitant procedures . Two patients (5%) presented with native active valve endocarditis . RESULTS: There was no hospital mortality or valve-related hospital morbidity . Blood silver concentrations peaked shortly after surgery and then decreased during the postoperative period . Average levels were consistently below 4 parts per billion (ppb) . Levels below 10 ppb are considered normal . Follow up was 95% complete . There were no recurrent or new cases of endocarditis . CONCLUSION: These clinical data indicate that the SJM Masters Series valve with Silzone coating performs well . No adverse effects of the silver coating could be detected, and there were no valve-related complications.

Proc Natl Acad Sci U S A, 2000 Feb 15, 97(4), 1938 - 43
The epidemiology of antibiotic resistance in hospitals: paradoxes and prescriptions; Lipsitch M et al.; A simple mathematical model of bacterial transmission within a hospital was used to study the effects of measures to control nosocomial transmission of bacteria and reduce antimicrobial resistance in nosocomial pathogens . The model predicts that: (i) Use of an antibiotic for which resistance is not yet present in a hospital will be positively associated at the individual level (odds ratio) with carriage of bacteria resistant to other antibiotics, but negatively associated at the population level (prevalence) . Thus inferences from individual risk factors can yield misleading conclusions about the effect of antibiotic use on resistance to another antibiotic . (ii) Nonspecific interventions that reduce transmission of all bacteria within a hospital will disproportionately reduce the prevalence of colonization with resistant bacteria . (iii) Changes in the prevalence of resistance after a successful intervention will occur on a time scale of weeks to months, considerably faster than in community-acquired infections . Moreover, resistance can decline rapidly in a hospital even if it does not carry a fitness cost . The predictions of the model are compared with those of other models and published data . The implications for resistance control and study design are discussed, along with the limitations and assumptions of the model.

Am Surg, 2000 Feb, 66(2), 162 - 5
Soft tissue infections; Stone HH; Soft tissue infections are almost routinely the product of direct microbe inoculation through a bridged protective skin . Day of onset and clinical presentation reflect the causative pathogen(s) and course that should be taken in treatment . Exclusive of chronic states, only in the most fulminating cases are culture and antimicrobial drugs of any real value.

Am Surg, 2000 Feb, 66(2), 157 - 61
Evaluation and management of tertiary peritonitis; Malangoni MA; Tertiary or recurrent peritonitis can occur after any operation for secondary bacterial peritonitis . The major risk factors for the development of tertiary peritonitis include malnutrition, a high Acute Physiology and Chronic Health Evaluation II score, the presence of organisms resistant to antimicrobial therapy, and organ system failure . Most patients with tertiary peritonitis will have fever and leukocytosis, even though other signs of infection may be absent . The management of tertiary peritonitis should include the provision of appropriate physiologic support, the administration of antimicrobial therapy, and operation or intervention to control the source of contamination and to decrease the bacterial load . Antibiotic-resistant organisms and bacteremia are present more commonly and mortality is greater in patients with tertiary peritonitis . Early recognition and effective intervention are critical to achieving a successful outcome.

Am Surg, 2000 Feb, 66(2), 105 - 11
Prophylactic antibiotics in surgery and surgical wound infections; Polk HC Jr et al.; Wound infection remains a considerable cause of morbidity and mortality among surgical patients, despite the relative success of prophylactic antibiotics . In modern efforts to control healthcare costs while improving the quality of patient care, we must not overlook the basic principles of wound infections and their appropriate treatment . Predisposing factors for the development of surgical wound infection include the creation of a surgical wound, the presence of bacteria, and a susceptible host . The selection of an appropriate antimicrobial drug depends on the identification of the most likely pathogens associated with a given procedure, as well as the expected antibiotic susceptibility of those pathogens . Ideally, a prophylactic antibiotic should achieve high peak tissue concentration at the site of the wound before the first incision and should be maintained until the time of closure . Currently, the administration of prophylactic antibiotics is indicated for contaminated and clean-contaminated wounds . Despite the proven effectiveness of antibiotic prophylaxis, many researchers would argue that contemporary dosing regimens should be reevaluated . The debates concerning the dosage and timing of ideal prophylactic administration are likely to continue.

J Lab Clin Med, 2000 Feb, 135(2), 122 - 8
Gene therapy for chronic granulomatous disease; Kume A et al.; Recent progress in the development of gene therapy for chronic granulomatous disease (CGD), an inherited immunodeficiency syndrome, is reviewed . This disorder results from defects in any of the four genes encoding essential subunits of respiratory burst oxidase, the superoxide-generating enzyme complex in phagocytic leukocytes . The absence of respiratory burst oxidants results in recurrent bacterial and fungal infections and can also be complicated by the formation of inflammatory granulomas . Although current management, including prophylactic use of antimicrobial agents and interferon-gamma, has significantly improved its prognosis, CGD continues to be associated with significant morbidity and mortality from life-threatening infections and complications . Allogeneic bone marrow transplantation can provide a life-long cure of the disease, but difficulty in finding suitable donors and risks associated with this procedure have limited its application . Recently CGD has emerged as a promising candidate for gene therapy targeted at the hematopoietic system . CGD mouse models have been developed with gene targeting technology, and preclinical studies in these animals with recombinant retroviral vectors have demonstrated the appearance of functionally normal neutrophils and increased resistance against pathogens such as Aspergillus . Although the murine studies have provided a promise of long-term cure of patients by gene transfer, phase I clinical studies in a limited number of patients with CGD with such vectors have yet to produce a clinically relevant number of corrected neutrophils for extended time periods . Efforts are ongoing to improve gene transfer efficiency into human hematopoietic stem/progenitor cells and to achieve better engraftment of the gene-corrected stem cells.

Dig Dis Sci, 2000 Jan, 45(1), 68 - 76
Effect of pretreatment antibiotic resistance to metronidazole and clarithromycin on outcome of Helicobacter pylori therapy: a meta-analytical approach; Dore MP et al.; Our purpose was to define the effect of pretreatment Helicobacter pylori resistance to metronidazole or to clarithromycin on the success of antimicrobial therapy . We used 75 key words to perform a literature search in MEDLINE as well as manual searches to identify clinical treatment trials that provided results in relation to H . pylori susceptibility to metronidazole and clarithromycin or both during the period 1984-1997 (abstracts were not included) . Meta-analysis was done with both fixed- and random-effect models; results were shown using Galbraith's radial plots . We identified 49 papers with 65 arms for metronidazole (3594 patients, 2434 harboring H . pylori strains sensitive to metronidazole and 1160 harboring resistant strains) . Metronidazole resistance reduced effectiveness by an average of 37.7% (95% CI = 29.6-45.7%) . The variability in the risk difference for metronidazole was 122.0 to -90.6 and the chi-square value for heterogeneity was significant (P<0.001) . Susceptibility tests for clarithromycin were performed in 12 studies (501 patients, 468 harboring H . pylori strains sensitive to clarithromycin and 33 harboring resistant strains) . Clarithromycin resistance reduced effectiveness by an average of 55% (95% CI = 33-78%) . We found no common factors that allowed patients to be divided into subgroups with additional factors significantly associated with resistance . In conclusion, metronidazole or clarithromycin pretreatment resistant H . pylori are the main factors responsible for treatment failure with regimens using these compounds . If H . pylori antibiotic resistance continues to increase, pretherapy antibiotic sensitivity testing might become necessary in many regions.

Trop Gastroenterol, 1999 Jul-Sep, 20(3), 123 - 7
Gastric protection against cold restraint stress-induced lesions by amoxycillin in rats; Ali AT et al.; AIMS: Recent investigations have shown that amoxycillin possesses gastric protection properties in addition to its known antimicrobial effects . Therefore, this study was undertaken to investigate the potential gastric protection effects of amoxycillin and to determine its possible mechanism(s) of action in rats . METHODS: The cold restraint stress model was used to produce gastric mucosal lesions . The gastric secretion studies were undertaken by using Shay's pylorus ligation technique . The antioxidant effect was studied by luminol dependent chemiluminescence technique in vitro . RESULTS: Amoxycillin dose-dependently prevented cold restraint stress-induced mucus depletion and afforded protection . It inhibited indomethacin-stimulated gastric acid secretion with a high dose without affecting basal secretion . Furthermore, amoxycillin dose-dependently inhibited the phorbol myristate acetate-stimulated luminol-dependent chemiluminescence responses of isolated human poylmorphonuclear leukocytes in vitro . CONCLUSIONS: These results suggest that mechanisms of gastric protection effects of amoxycillin may include inhibition of stimulated acid secretion, prevention of depletion of mucus and antioxidant properties.

J Invest Dermatol, 2000 Mar, 114(3), 602 - 8
Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity; Murphy JE et al.; As our primary interface with the environment, the skin is constantly subjected to injury and invasion by pathogens . The fundamental force driving the evolution of the immune system has been the need to protect the host against overwhelming infection . The ability of T and B cells to recombine antigen receptor genes during development provides an efficient, flexible, and powerful immune system with nearly unlimited specificity for antigen . The capacity to expand subsets of antigen-specific lymphocytes that become activated by environmental antigens (memory response) is termed "acquired" immunity . Immunologic memory, although a fundamental aspect of mammalian biology, is a relatively recent evolutionary event that permits organisms to live for years to decades . "Innate" immunity, mediated by genes that remain in germ line conformation and encode for proteins that recognize conserved structural patterns on microorganisms, is a much more ancient system of host defense . Defensins and other antimicrobial peptides, complement and opsonins, and endocytic receptors are all considered components of the innate immune system . None of these, however, are signal-transducing receptors . Most recently, a large family of cell surface receptors that mediate signaling through the NF-kappaB transcription factor has been identified . This family of proteins shares striking homology with plant and Drosophila genes that mediate innate immunity . In mammals, this family includes the type I interleukin-1 receptor, the interleukin-18 receptor, and a growing family of Toll-like receptors, two of which were recently identified as signal-transducing receptors for bacterial endotoxin . In this review, we discuss how interleukin-1 links the innate and acquired immune systems to provide synergistic host defense activities in skin.

Eur J Biochem, 2000 Mar, 267(5), 1447 - 54
Structure-function relationships of temporins, small antimicrobial peptides from amphibian skin; Mangoni ML et al.; Temporins, antimicrobial peptides of 10-13 residues, were isolated from secretions of Rana temporaria {Simmaco, M., Mignogna, G., Canofeni, S., Miele, R., Mangoni, M.L . & Barra, D . (1996) Eur . J . Biochem . 242, 788-792} . These molecules are specific to this amphibian species, which is also able to secrete on its skin other antimicrobial peptides similar to those found in different Rana species . The effect of temporins A, B and D (13 residues, net charge +2), and H (10 residues, net charge +1 and +2, respectively) against both artificial membranes of differing lipid composition and bacteria has been investigated in order to gain insight into their mechanisms of action . The results indicate that: the lytic activity of temporins is not greatly affected by the membrane composition; temporins A and B allow the leakage of large-size molecules from the bacterial cells; temporin H renders both the outer and inner membrane of bacteria permeable to hydrophobic substances of low molecular mass; and temporin D, although devoid of antibacterial activity, has a cytotoxic effect on erythrocytes . The results allow important conclusions to be drawn about the minimal structural requirements for lytic efficiency and specificity of temporins.

Ann Intern Med, 2000 Mar 7, 132(5), 391 - 402
Prevention of intravascular catheter-related infections; Mermel LA; PURPOSE: To review the literature on prevention of intravascular catheter-related infections . DATA SOURCES: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles . Primary authors were contacted directly if data were incomplete . STUDY SELECTION: Studies met the following criteria unless otherwise stated: Trials were prospective and randomized; catheters were inserted into new sites, not into old sites over guidewires; catheter cultures were done by using semi-quantitative or quantitative methods; and, for prospective studies, catheter-related bloodstream infection was confirmed by microbial growth from percutaneously drawn blood cultures that matched catheter cultures . DATA EXTRACTION: Data on population, methods, preventive strategy, and outcome (measured as catheter-related bloodstream infections) were gathered . The quality of the data was graded by using preestablished criteria . DATA SYNTHESIS: The recommended preventive strategies with the strongest supportive evidence are full barrier precautions during central venous catheter insertion; subcutaneous tunneling short-term catheters inserted in the internal jugular or femoral veins when catheters are not used for drawing blood; contamination shields for pulmonary artery catheters; povidone-iodine ointment applied to insertion sites of hemodialysis catheters; specialized nursing teams caring for patients with short-term peripheral venous catheters, especially at institutions with a high incidence of catheter-related infection; no routine replacement of central venous catheters; antiseptic chamberfilled hub or hub-protective antiseptic sponge for central venous catheters; and use of chlorhexidine-silver sulfadiazine-impregnated or minocycline-rifampin-impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies that do not incorporate antimicrobial agents (for example, maximal barrier precautions) . CONCLUSIONS: Simple interventions can reduce the risk for serious catheter-related infection . Adequately powered randomized trials are needed.

Eur J Clin Microbiol Infect Dis, 1999 Dec, 18(12), 915 - 7
Antimicrobial susceptibilities and biotypes of Arcanobacterium haemolyticum blood isolates; Carlson P et al.; Isolates obtained from the blood of ten patients with Arcanobacterium haemolyticum septicaemia were biotyped as smooth or rough using morphological and biochemical criteria, and their susceptibilities to 18 antibacterial agents were determined . Nine of the clinical cases included here have not been reported previously and are discussed in brief . One of the strains was highly resistant to macrolides and clindamycin . With one exception, the strains belonged to the smooth biotype . The data presented here indicates that the treatment of systemic Arcanobacterium haemolyticum infections should be based on the antibacterial susceptibility profiles of individual strains and on the site of the infection.

Eur J Clin Microbiol Infect Dis, 1999 Dec, 18(12), 885 - 9
Efficacy of treatment with paromomycin, azithromycin, and nitazoxanide in a patient with disseminated cryptosporidiosis; Giacometti A et al.; A 24-year-old HIV-positive heterosexual woman with disseminated cryptosporidiosis was monitored from January 1998 to May 1999 . During this period, consecutive stool, sputum, and bile examinations showed the constant presence of Cryptosporidium oocysts . Although the patient was repeatedly treated with oral paromomycin and azithromycin and, finally, nitazoxanide, her condition continued to deteriorate . In order to monitor the in vitro susceptibility of the parasite, specimens from various sites were collected periodically . When the first clinical isolate was tested, the antimicrobial agents used (azithromycin at a concentration of 8 mg/l, paromomycin at of 1 mg/ml, and nitazoxanide at 10 mg/l) produced a decrease in parasite counts of 26.5%, 63.4%, and 67.2%, respectively . Subsequent isolates of Cryptosporidium parvum showed similar susceptibilities . This case demonstrates that failure of clinical treatment corresponded to inadequate growth inhibition of the parasite in vitro.

Drugs Aging, 1999, 15 Suppl 1, 21 - 30
Pneumococcal vaccination for older adults: the first 20 years; Fedson DS; During the 20 years following its licensure, pneumococcal vaccine has not been widely used . Although the vaccine was shown to be efficacious in South African gold miners, clinical trials of 'pneumonia vaccine' in older adults that have attempted to demonstrate vaccine efficacy in preventing pneumonia have been inconclusive . Retrospective studies have convincingly demonstrated the effectiveness of vaccination in preventing invasive pneumococcal disease, but these findings have only gradually gained acceptance, largely because some observers reject the findings of observational studies or fail to appreciate the importance of invasive disease . In the 1980s, pneumococcal vaccine was used only in the US, but other countries began vaccination in the mid-1990s, in part due to a better understanding of the disease and the vaccine, but also because of concern about antimicrobial resistance . With greater understanding of the global importance of pneumococcal disease and the promise of conjugate and protein vaccines, during the next 20 years pneumococcal vaccines will become the most important vaccines for adults and children worldwide.

Am J Infect Control, 2000 Feb, 28(1), 57 - 65
Expanding the role of the infection control professional in the cost-effective use of antibiotics; Minooee A et al.; There is a growing demand that health care expenses be contained and that excessive and inappropriate use of antibiotics be eliminated . At the University of California, San Diego Medical Center, strategies aimed at controlling drug usage and subsequently reducing costs have been implemented and found to be effective . Mechanisms designed to achieve such goals without diminishing quality of care involve expanding the role of the infection control professional (ICP) while implementing antibiotic control stratagems such as antimicrobial utilization teams, antibiotic order sheets, audits of use, automatic stop orders, computer-assisted management, drug use reviews, educational efforts, formulary practice, restricted drug policies, and target drug monitoring . The infection control professional, as well as other members of the antimicrobial utilization team, contributes to the promotion of the appropriate use of antibiotics in part by identifying individual cases in which antibiotics might be used inappropriately, such as for the treatment of colonization rather than infection or when appropriate microbiologic testing has not been carried out.

Gen Dent, 1999 Mar-Apr, 47(2), 172 - 8, 181
Site specific delivery of antimicrobial agents for periodontal disease; Ciancio SG; Controlled release delivery systems have become available for the sustained delivery of antimicrobial agents directly to the periodontal pocket . These systems have shown clinical efficacy in periodontal therapy both as adjunctive treatments and as stand-alone therapies . A review of the current state-of-the-art of site specific delivery of antimicrobial agents for the treatment of periodontal disease is provided.

Gen Dent, 1999 Mar-Apr, 47(2), 164 - 8; quiz 169-70
Irrigation with antimicrobial agents for the treatment of periodontitis--is it effective?
Gustke CJ.
Subgingival irrigation has been proposed as a beneficial adjunct to scaling and root planing or ultrasonic scaling . The most commonly investigated agents are iodine and chlorhexidine . Clinical studies from the past 15 years are reviewed to determine the real benefits of antimicrobial irrigants in conjunction with root planning . With knowledge of the treatment protocols and results of these clinical studies, the clinician is equipped with a biologic rationale for his treatment decisions in nonsurgical periodontics.

Int Arch Allergy Immunol, 2000 Jan, 121(1), 2 - 9
Genetic and environmental factors contributing to the onset of allergic disorders; Parronchi P et al.; Evidence has been accumulated to suggest that allergen-reactive Th2 cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in allergic inflammation . Recently, chemokines and chemokine receptors involved in such Th2-type response have been also defined . Th2 cells represent the polarized arm of the effector-specific responses that contribute to the protection against gastrointestinal nematodes and act as regulatory cells for chronic and/or excessive Th1-mediated responses . Th2 cells are generated from precursor naive Th cells when they encounter the specific antigen in an IL-4-containing microenvironment . The question of how these Th2 cells are selected in atopic patients is also unclear . Both the nature of the T cell receptor signalling provided by the allergen peptide ligand and a disregulation of IL-4 production likely concur to determine the Th2 profile of allergen-specific Th cells, but the genetic unbalanced IL-4 production is certainly overwhelming . Some gene products selectively expressed in Th2 cells or selectively controlling the expression of IL-4 have recently been described . These findings allow to suggest that the upregulation of genes controlling IL-4 expression and/or abnormalities of regulatory mechanisms of Th2 development and/or function may be responsible for Th2 responses against allergens in atopic people . The increasing prevalence of allergy in developed countries suggests that environmental factors acting either before or after birth also contribute to regulate the development of Th2 cells and/or their function . The reduction of infectious diseases in early life due to increasing vaccinations, antimicrobial treatments as well as changed lifestyle are certainly important in influencing the individual outcome in the Th response to ubiquitous allergens . Moreover, the recent evidence that bacterial DNA or oligodeoxynucleotides containing unmethylated 'CpG motifs' promote the development of Th1 cells via the production of immunomodulatory cytokines (namely IL-12, IL-18 and IFNs) by professional antigen-presenting cells confirms previous epidemiological data . The new insight into the pathophysiology of T cell responses in atopic diseases provides exciting opportunities for the development of novel immunotherapeutic strategies .

J Perinatol, 1999 Jun, 19(4), 275 - 7
Ureaplasma/Mycoplasma-infected amniotic fluid: pregnancy outcome in treated and nontreated patients; Berg TG et al.; OBJECTIVE: To determine if treatment of a positive amniotic fluid culture for mycoplasmal colonization obtained at genetic amniocentesis is associated with improved pregnancy outcome . STUDY DESIGN: A retrospective analysis of 2718 genetic amniocentesis specimens cultured for Ureaplasma/Mycoplasma was undertaken . Specimens were obtained between March 1993 and January 1997 . The Irvine culture kit was used to culture all specimens . Data collected included indication for amniocentesis, gestational age at amniocentesis, karyotype, gestational age at delivery, pregnancy outcome, and any antimicrobial treatment . RESULTS: During this time period 44 patients were found to be culture-positive for Ureaplasma/Mycoplasma . Thirty-five were treated with oral erythromycin . Mid-trimester loss was 11.4% and 44.4% (p = 0.04) in the treated and untreated groups, respectively . Preterm delivery was similar in the two groups, 19.4% and 20% (p = NS) . CONCLUSION: Treatment of an amniotic mycoplasmal colonization with erythromycin was associated with fewer mid-trimester losses after genetic amniocentesis . Preterm delivery rates between the two groups were similar, which may indicate recolonization.

J Perinatol, 1999 Jan, 19(1), 31 - 9
Skin care practices in the neonatal nursery: a clinical survey; Siegfried EC et al.; OBJECTIVE: To survey the details of skin care practices in a sample of level I, II, and III nurseries in the United States . DESIGN: A survey conducted by written questionnaire, personal inspection, and phone contact . PARTICIPANTS: Information was obtained from staff physicians and nurses about routine neonatal skin care practices, including bathing, cord care, emollient use, diapering, use of antimicrobial skin preparations, management of intravenous infiltration, approach to diaper rash, and methods used to minimize transcutaneous water loss . SETTING: Fifteen nurseries from twelve hospitals in four states were surveyed . RESULTS: Among the nurseries surveyed, we found no uniform approach to skin care . Only two individual maneuvers were consistently performed in all the nurseries: criteria for bathing and skin antisepsis with povidone-iodine . Other than these, a wide range of practices and products were used, some with a high ratio of risk and/or cost to benefit . CONCLUSION: A better understanding of the principles of infant skin care and a more uniform approach to skin care in the neonatal nursery can minimize risks and costs to this special population of patients.

J Comp Pathol, 2000 Feb-Apr, 122(2-3), 217 - 22
Isolation of Actinobacillus seminis from the genital tract of rams in spain; de la Puente-Redondo VA et al.; Actinobacillus seminis isolates were cultured from the semen (two isolates) and the left testis (one isolate) of two one-year-old rams in Leon, Spain . One animal showed lesions of chronic unilateral orchitis and epididymitis while the other appeared to suffer a subclinical infection and only a moderate number of pleomorphic rods and inflammatory cells were present in its semen . The isolates were biochemically similar to the A . seminis type strain NCTC 10851 and two other European A . seminis isolates, except that they produced acid from sorbitol; their identity was confirmed by arbitrarily primed polymerase chain reaction . The isolates were also tested against 30 antimicrobial agents, and only marbofloxacin was found active against all of them . As far as is known, this is the first report of A . seminis isolation from rams in southern Europe.

Am J Contact Dermat, 2000 Mar, 11(1), 53 - 6
Allergic contact dermatitis caused by parabens: 2 case reports and a review; Mowad CM; Parabens, methyl, ethyl, propyl, benzyl, and butyl, are the most common preservatives in use today . They are the alkyl esters of p-hydroxybenzoic acid and are used extensively because they are relatively nonirritating and nontoxic and offer good antimicrobial coverage . Testing for paraben allergen can be done by patch testing . Two cases of allergic contact dermatitis (ACD) to parabens are used to discuss the background of parabens, their allergenicity, patch testing issues, and several "paraben paradoxes." Although ACD to parabens has been reported, given the widespread use, it is relatively uncommon . Because of their low rate of allergenicity and their favorable preservative profile and efficacy, parabens remain the number one preservative in use.

Pediatr Nephrol, 2000 Feb, 14(2), 111 - 3
Fatal disseminated Nocardia farcinica infection in a renal transplant recipient; Rinaldi S et al.; Six years after a renal cadaver transplant, a 20-year-old girl developed multiple painful cutaneous abscesses and bilateral pneumonia secondary to Nocardia farcinica infection . Despite broad in vitro sensitivity to several antibiotic agents and aggressive medical treatment, the patient failed to respond and died after 10 weeks of therapy . We conclude that Nocardia farcinica is a very aggressive organism in immunocompromised patients and is often resistant to antimicrobial agents.

Hua Xi Yi Ke Da Xue Xue Bao, 1997 Dec, 28(4), 365 - 8
{Penetration of ciprofloxacin and cefoperazone into human pancreas}; Jiang L et al.; Major pancreatic infection is responsible for more than 80% of deaths in patients with acute pancreatitis . Therefore, the role of antimicrobial drugs in the prevention and treatment of secondary parcreatic infection is very important . The choice of antimicrobial drugs must be based upon the ability of the drug to exceed the therapeutic concentration in pancreas for the common pathogens . The penetration of ciprofloxacin and cefoperazone into pancreas was investigated in ten patients who had undergone pancreatoduodenectomy . The pancreatic juice was temporarily diverted to the exterior via a panoreatic duct catheter . The pancreatic tissue was obtained intraoperatively and pancreatic juice was drained postoperatively . The antimicrobial drug concentrations were determined by high-performance liquid chromatography . The concentrations of ciprofloxacin and cefoperazone in pancreatic juice were 44% and 17%, respectively, of those in serum, and exceeded the in vitro concentration (MIC-90) for most bacteria associated with pancreatic infections . The result indicates that ciprofloxacin and cefoprazone appear to be appropriate for both prophylaxis and therapy of secondary pancreatic infections.

Arzneimittelforschung, 2000 Jan, 50(1), 55 - 9
Synthesis, antibacterial, antifungal and anti-HIV evaluation of Schiff and Mannich bases of isatin and its derivatives with triazole; Pandeya SN et al.; Isatin (indole 2,3-dione) and its 5-chloro and 5-bromo derivatives have been reacted with 3-(4'-pyridyl)-4-amino-5-mercapto-4-(H)-1,2,4-triazole to form Schiff bases and the N-Mannich bases of these compounds were synthesised by reacting them with formaldehyde and several secondary amines . Their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analysis . Investigation of antimicrobial activity of compounds was done by agar dilution method against 27 pathogenic bacteria, 8 pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells . Among the compounds tested 1-(piperidinomethyl) 5-bromo 3-{3'-(4"-pyridyl)-5'-mercapto-4'-(H)-1',2',4'-triazol 4'-yl}imino isatin showed the most favourable antimicrobial activity.

Arzneimittelforschung, 2000 Jan, 50(1), 48 - 54
Synthesis and biological evaluation of indole containing derivatives of thiosemicarbazide and their cyclic 1,2,4-triazole and 1,3,4-thiadiazole analogs; Varvaresou A et al.; New indolic derivatives of thiosemicarbazides and some cyclic 1,2,4-triazol-5-thione analogs were synthesized . The newly synthesized compounds as well as some indole containing thiosemicarbazides, 1,2,4-triazoles and 1,3,4- thiadiazoles, which have been reported previously, were investigated for antimicrobial, antifungal and antiphage activity . Certain thiosemicarbazide derivatives and the corresponding cyclic 1,2,4-triazole analogs showed selective antimicrobial or antifungal activity, while they lack any antiphage activity . Antiphage activity was detected for one compound, bearing the 1,3,4-thiadiazole nucleus . The selectively active compounds cover a wide range of lipophilicity . Structure-activity relations show a remarkably similarity in the antimicrobial and antifungal behaviour of the thiosemicarbazides and their cyclic triazo-thien-5-yl analogs, while alpha-naphtyl substitution in the non indolic portion of the molecule is favorable . C5 substitution on the indolic nucleus may also be critical for selective activity.

Mayo Clin Proc, 2000 Feb, 75(2), 200 - 14
Clinical aspects of antimicrobial resistance; Virk A et al.; Soon after penicillin was introduced into clinical use, an enzyme (penicillinase) that inactivated it was discovered . Since then, the variety of antimicrobial agents has increased substantially, along with a parallel increase in resistant pathogenic microorganisms . Resistance is now recognized against all available antimicrobial agents . Factors influencing the emergence of resistance include indiscriminate use of antibiotics, prolonged hospitalizations, increasing numbers of immunocompromised patients, and medical progress resulting in increased use of invasive procedures and devices . This article provides an update on clinical aspects of a few commonly found resistant microorganisms relevant to day-to-day clinical practice . A discussion of all resistant organisms is beyond the scope of this report . Both viral and mycobacterial resistance have been addressed in previous articles in this symposium.

Ann N Y Acad Sci, 1999, 894, 37 - 43
Biological warfare training . Infectious disease outbreak differentiation criteria; Noah DL et al.; The threat of biological terrorism and warfare may increase as the availability of weaponizable agents increase, the relative production costs of these agents decrease, and, most importantly, there exist terrorist groups willing to use them . Therefore, an important consideration during the current emphasis of heightened surveillance for emerging infectious diseases is the capability to differentiate between natural and intentional outbreaks . Certain attributes of a disease outbreak, while perhaps not pathognomic for a biological attack when considered singly, may in combination with other attributes provide convincing evidence for intentional causation . These potentially differentiating criteria include proportion of combatants at risk, temporal patterns of illness onset, number of cases, clinical presentation, strain/variant, economic impact, geographic location, morbidity/mortality, antimicrobial resistance patterns, seasonal distribution, zoonotic potential, residual infectivity/toxicity, prevention/therapeutic potential, route of exposure, weather/climate conditions, incubation period, and concurrence with belligerent activities of potential adversaries.

Jpn J Infect Dis, 1999 Oct, 52(5), 183 - 97
Association of Helicobacter pylori with gastroduodenal diseases; Hirai Y et al.; Helicobacter pylori was first cultured in vitro in 1982 . This bacterium is a spiral gram-negative rod which grows under microaerophilic conditions . The ecological niche is the mucosa of the human stomach which had been thought to be aseptic before the discovery of this bacterium . This organism causes a long-lasting infection throughout a person's life if there is no medical intervention . Numerous persons are infected with the organism around the world, and the rate of infection in Japan is nearly 50% of the population . However, the route of infection remains unclear because the organism has not been isolated from any environment other than several animals . H . pylori is now recognized as a causative agent of gastritis and peptic ulcers . Though gastritis, and especially chronic active gastritis, is observed at least histologically in all persons with H . pylori, peptic ulcers develop in only some infected persons . Specific factors in the host and/or the bacteria are needed for the development of peptic ulcer disease . Furthermore, H . pylori is considered to be related to the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, especially those of low grade . Also, H . pylori infection is a major determinant for initiating the sequence of events leading to gastric cancer . In some patients with low-grade gastric MALT lymphoma, the eradication of H . pylori led to a regression of lesion . Gastric cancer has been induced in Mongolian gerbils with long-term H . pylori infection . The combinations of drugs, which consist of an antisecretory agent (acid-suppressing agent) and antimicrobial agents, are used for the eradication of the organism . Eradication therapy is recommended at least for patients with peptic ulcers.

Curr Opin Microbiol, 2000 Feb, 3(1), 16 - 22
Signaling mechanisms in the antimicrobial host defense of Drosophila; Imler JL et al.; Drosophila has appeared in recent years as a powerful model to study innate immunity . Several papers published in the past year shed light on the role of the three Rel proteins Dorsal, Dif and Relish in the regulation of antimicrobial peptide expression . In addition, the discovery that a blood serine protease inhibitor is involved in the control of the antifungal response indicates that Toll is activated upon triggering of a proteolytic cascade and does not function as a Drosophila pattern recognition receptor.

Biochem Biophys Res Commun, 2000 Feb 16, 268(2), 333 - 6
Antimicrobial peptide of korean native goat lactoferrin and identification of the part essential for this activity; Kimura M et al.; The antimicrobial activity of lactoferrin isolated from Korean native goat (KN goat) milk was studied and its antimicrobial domain was identified using synthetic peptides . Antimicrobial activity was assayed by a micro-method using 96-well microplates and a microplate reader . The amino acid sequence of the antimicrobial domain was suggested to be YQWQRRMRKLGAPSIT and this sequence corresponds to amino acid residues 20 to 35 of KN goat lactoferrin . Five peptides with certain amino acid residues deleted were synthesized in an effort to identify the residues essential for antimicrobial activity and it was found that the part with the sequence RRMRK (24-28) is the region most important for this activity . On the other hand, the conformation of the peptides did not influence the antimicrobial activity .

Antimicrob Agents Chemother, 2000 Mar, 44(3), 676 - 81
Flow cytometric monitoring of antibiotic-induced injury in Escherichia coli using cell-impermeant fluorescent probes; Mortimer FC et al.; Three fluorescent nucleic acid binding dyes-propidium iodide, TO-PRO-1, and SYTOX green-were evaluated, and their abilities to distinguish between bacterial cells with and without an intact cytoplasmic membrane were compared . Each dye was readily able to discriminate between healthy and permeabilized cells of Escherichia coli, although SYTOX green showed a greater enhancement in fluorescence intensity on staining-compromised, as opposed to healthy, cells in log-phase growth, than either PI or TO-PRO-1 . Flow cytometric analysis of E . coli stained with these dyes after exposing them to several antimicrobial agents showed that all three dyes were able to detect antimicrobial action . Notably, however, the intensity of the cell-associated fluorescence was related to the mechanism of action of the antimicrobial agent . Large changes in fluorescence intensity were observed for all the dyes subsequent to beta-lactam antibiotic action, but smaller changes (or no change) were seen subsequent to exposure to antimicrobials acting directly or indirectly on nucleic acid synthesis . Furthermore, cell-associated fluorescence did not relate to loss of viability as determined by plate counts . Despite offering much insight into antimicrobial mechanisms of action, these fundamental problems become relevant to the development of rapid antimicrobial susceptibility tests if colony formation is used as the standard.

Ann Pharmacother, 2000 Feb, 34(2), 154 - 60
Economic impact of standardized orders for antimicrobial prophylaxis program; Frighetto L et al.; OBJECTIVE: To assess the effect and economic impact of an intervention aimed at standardizing the timing of preoperative antimicrobial prophylaxis from the perspective of a major teaching hospital . DESIGN: A pre/post study design in which a random sample of 60 procedures from a 12-month period in the preintervention phase were reviewed . A comparative sample of 60 procedures during a seven-month postintervention phase was selected . For each prophylactic course, preoperative dose administration details were classified as early (>2 h prior to incision), on time (0-2 h prior), delayed (0-3 h after), or late (>3 after) . To determine the economic impact of this intervention, we used a predictive decision analytic model using institutional costs and the published probabilities of inpatient surgical wound infections (SWIs) following administration of antimicrobials timed according to the above criteria . Two conditions were analyzed: (1) an interdisciplinary two-stage therapeutic interchange program involving staff education and modification of preoperative antimicrobial orders to ensure timely administration and (2) no intervention . SETTING: An 1100-bed tertiary care, university-affiliated institution . PATIENTS: 120 randomly selected procedures involving inpatients who received a preoperative antibiotic . OUTCOME MEASURES: Differences in preoperative antimicrobial timing and cost avoidance associated with the intervention . RESULTS: In the preintervention phase, 68% of prophylactic courses were on time, 22% were early, and the balance were delayed or late . The incidence of on-time prophylaxis increased to 97% during the postintervention phase (p = 0.001) . Operating room staff involvement in antimicrobial administration increased from 57% to 92% (p = 0.001) . Based on a setup and annual intervention cost of $9100 CAN ($1 CAN = $0.68 US), an annual inpatient SWI avoidance of 51 cases, an average infection-associated extended hospital stay of four days, and an average treatment cost of $1957 CAN per inpatient SWI, we estimated that 153 hospital days were avoided and there was an annual cost avoidance of $90 707 CAN ($1779 CAN saved per inpatient infection avoided) due to this intervention . Using sensitivity analyses, no plausible changes in the base case estimates altered the results of the economic model . CONCLUSIONS: An interdisciplinary approach to optimizing the timing of preoperative antimicrobial doses can impact positively on practice patterns and result in substantial cost avoidance . Costs incurred to implement such an intervention are small when compared with the annual cost avoidance to the institution.

Drug Discov Today, 2000 Mar, 5(3), 107 - 114
Integrated bacterial genomics for the discovery of novel antimicrobials; Loferer I I et al.; Sequencing of bacterial genomes has been progressing with breathtaking speed . Currently, the genomes of 23 bacterial species are sequenced, with approximately 40 more sequencing projects in progress . Industrial research is now facing the challenge of translating this information efficiently into drug discovery . This review will summarize the impact of bacterial genomics, bioinformatics and second-generation genomic technologies on target identification, assay development, lead optimization and compound characterization.

Am J Health Syst Pharm, 2000 Feb 1, 57(3), 268 - 74
Outcomes of an antimicrobial control program in a teaching hospital; Gentry CA et al.; The clinical outcomes and cost-effectiveness of an antimicrobial control program (ACP) were studied . The impact of an ACP in a teaching hospital was analyzed by comparing clinical outcomes and intravenous antimicrobial costs over two two-year periods, the two years before the program and the first two years after the program's inception . Admission baseline data, length of stay, mortality, and readmission rates were gathered for each patient . Patients were identified by using the International Classification of Diseases . Multivariate logistic regression models were constructed for mortality and for lengths of stay of 12 or more days . The acquisition costs of intravenous antimicrobial agents for the second baseline year and the entire program period were tabulated and compared . The average daily inpatient census was determined . The ACP was associated with a 2.4-day decrease in length of stay and a reduction in mortality from 8.28% to 6.61% . Rates of readmission for infection within 30 days of discharge remained about the same . Inpatient pharmacy costs other than intravenous antimicrobials decreased an average of only 5.7% over the two program years, but the acquisition cost of intravenous antimicrobials for both program years yielded a total cost saving of $291,885, a reduction of 30.8% . The institution's average daily census fell 19% between the second baseline year and the second program year . An ACP directed by a clinical pharmacist trained in infectious diseases was associated with improvements in inpatient length of stay and mortality . The ACP decreased intravenous antimicrobial costs and facilitated the approval process for restricted and nonformulary antimicrobial agents.

J Pept Sci, 2000 Jan, 6(1), 19 - 25
Chemical synthesis, characterization and activity of RK-1, a novel alpha-defensin-related peptide; Dawson NF et al.; The 32-residue peptide, RK-1, a novel kidney-derived three disulfide-bonded member of the antimicrobial alpha-defensin family, was synthesized by the continuous flow Fmoc-solid phase method . The crude, cleaved and S-reduced linear peptide was both efficiently folded and oxidized in an acidic solution of aqueous dimethyl sulfoxide . Following purification of the resulting product, it was shown by a variety of analytical techniques, including matrix assisted laser desorption time of flight mass spectrometry, to possess a very high degree of purity . The disulfide bond pairing of the synthetic peptide was determined by 1H-NMR spectroscopy and confirmed to be a Cys1-Cys6, Cys2-Cys4, Cys3-Cys5 arrangement similar to other mammalian alpha-defensin peptides . The synthetic RK-1 was also shown to inhibit the growth of Escherichia coli type strain NCTC 10418.

Am J Trop Med Hyg, 1999 Dec, 61(6), 885 - 8
An outbreak of West Nile fever among migrants in Kisangani, Democratic Republic of Congo; Nur YA et al.; In February 1998, an outbreak of acute febrile illness was reported from the Kapalata military camp in Kisangani, the Democratic Republic of Congo . The illness was characterized by an acute onset of fever associated with severe headache, arthralgia, backache, neurologic signs, abdominal pain, and coughing . In 1 individual, hemorrhagic manifestations were observed . The neurologic signs included an altered level of consciousness, convulsions, and coma . Malaria was initially suspected, but the patients showed negative blood films and failed to respond to antimicrobial drugs . A total of 35 sera collected from the military patients in the acute phase were tested for the presence of IgM against vector-borne agents . Serum IgM antibodies against West Nile fever virus were found in 23 patients (66%), against Chikungunya virus in 12 patients (34%), against dengue virus in 1 patient (3%), and against Rickettsia typhi in 1 patient (3%) . All sera were negative for IgM antibody against Rift Valley fever virus, Crimean Congo hemorrhagic fever virus, and Sindbis virus . These data suggest that infections with West Nile fever virus have been the main cause of the outbreak.

SAR QSAR Environ Res, 1999 Dec, 10(6), 509 - 32
Use of reversed-phase high-performance liquid chromatography in QSAR analysis of 2,4-dihydroxythiobenzanilide analogues; Jozwiak K et al.; Thiobenzanilides are found to show strong biological activity as antimicrobial, antimycotic, and tuberculostatic agents . In addition, they are relatively weakly toxic to higher organisms . A large set of new (N-phenyl-)-2,4-dihydroxybenzenecarbothioamide derivatives was obtained . Preliminary studies showed high microbiological action of some of them . In the process of chromatographic analysis, several different chromatographic parameters were obtained . In case of RP-HPLC, these parameters correspond to hydrophobicity of the solute . Obtained chromatographic parameters exhibited moderate correlation with calculated log P parameter . Linear dependence of bacteriostatic or fungostatic activity on lipophilicity was observed . The degree of correlation of different parameters was compared . The lipophilicity of analysed tioamides was the most important factor responsible for fungostatic and bacteriostatic activity . In comparison to methanol eluent system, chromatographic parameters obtained in acetonitrile system were better correlated with bioactivity . Conversely with the calculated log P values, the experimentally derived parameters exhibited significant higher correlation to fungostatic activity determined on dermatophytes . While in case of other tested microorganisms log P was comparably or sometimes slightly better correlated.

Pathol Biol (Paris), 1999 Dec, 47(10), 1071 - 4
{Surgical antibiotic prophylaxis: point evaluation of practices}; Lefflot S et al.; Compliance of prophylactic antimicrobial therapy (PAMT) in surgical patients with consensus-based recommendations was evaluated at the Montfermeil Hospital Center, France, in 1996, based on data for given days . All patients who had surgery on the study days were included . Data on the patient, surgery, and PAMT were collected . Practices were evaluated based on seven criteria: need for PAMT, type of drug used, dosage, time of first administration in relation to the time the incision was made, time of administration during surgery, administration time schedule, and total duration . Of the 93 patients who had surgery on one of the five study days, 59.1% received PAMT . All seven evaluation criteria were met in 68.2% of cases . Failure to adhere to the recommended time of first administration was the most common form of noncompliance.

Nurs Clin North Am, 2000 Mar, 35(1), 87 - 94
The judicious use of antibiotic agents in common childhood respiratory illness; Manning ML et al.; Increased bacterial resistance is caused most frequently by the widespread use of antimicrobial agents . Antimicrobial agents are often used inappropriately to treat common respiratory illnesses in children . This article discusses the judicious use of antimicrobials in the common cold, otitis media, acute sinusitis, pharyngitis, and bronchitis.

Biochem Biophys Res Commun, 2000 Jan 27, 267(3), 783 - 90
Marked increase in membranolytic selectivity of novel cyclic tachyplesins constrained with an antiparallel two-beta strand cystine knot framework; Tam JP et al.; We have developed a highly constrained 18-residue cyclic peptide template based on the antimicrobial peptide tachyplesin-1 that features an end-to-end peptide backbone and a cystine knot-like motif with three evenly spaced disulfide bonds to cross-brace the antiparallel beta-strands and to approximate an amphiphatic "beta-tile"-like structure . Six beta-tile analogs were prepared to correlate different topological patterns with membranolytic specificity . Their conformations and antimicrobial and hemolytic activities were compared with tachyplesin-1 and the recently discovered Rhesus monkey theta defensin (RTD) which contains similar beta-tile structural elements . The beta-tile peptides and RTD retained broad spectrum antimicrobial activities . In general, they were less active than tachyplesin-1 in 10 tested organisms but their activity increased under high-salt (100 mM NaCl) rather than in low-salt conditions . The beta-tile peptides are highly nontoxic to human erythrocytes with EC(25) ranging from 600 to 4000 microM . Collectively, our results show that the design of a highly rigid peptide template is useful for further analog study to dissociate antimicrobial activity from cytotoxicity which would be helpful in discovering clinical applications for peptide antibiotics .

Bioorg Med Chem Lett, 2000 Jan 17, 10(2), 115 - 8
Structure-activity relationships of trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenems . Part 2: J-111,225, J-114,870, J-114,871 and related compounds; Imamura H et al.; Through further derivatization of J-111,347 (1a), a trans-3,5-disubstituted pyrrolidinylthio-1beta-methylcarbapenem, undesired epileptogenicity in a rat intracerebroventricular assay (200 microg/rat) could be eliminated to afford J-111,225 (2a), J-114,870 (3a) and J-114,871 (3b) which preserved comparable broad antimicrobial activity.

Rev Stomatol Chir Maxillofac, 1999 Dec, 100(6), 299 - 305
Antimicrobial effectiveness of 2% glutaraldehyde versus other disinfectants for hospital equipment, in an in vitro test based on germ-carriers with a high microbial contamination; Herruzo-Cabrera R et al.; 2% glutaraldehyde is the reference disinfectant for hospital instruments . However, its high environmental toxicity makes desirable to search for alternatives . We compare the antimicrobial activity of 2% glutaraldehyde with 0.44% N-duopropenide (NDP), 0.66% NDP in 48 degrees alcoholic solution (NDP-alc), 0.13% glutaraldehyde-phenate, 1% or 3% persulphate (Virkon) and 0.1% or 0.5% chlorhexidine, using a model that mimics non-regular surface instruments contaminated with microbial strains (44 bacteria, 6 of which were Mycobacterium) . The contaminated carrier is soaked in the disinfectant solution . After 5 or 20 minutes contact the disinfectant is neutralized . The overall results on all microorganisms in 20 minutes, show similar antibacterial activity for 2% glutaraldehyde and 0.66% NDP-alc, followed by 0.44% NDP and after by the two concentrations of Virkon and 0.5% chlorhexidine . The 0.13% glutaraldehyde-phenate and 0.1% chlorhexidine exhibited significantly less effect than any other disinfectant . 0.66% NDP-alc was faster antimicrobial activity than 2% glutaraldehyde, destroying totally the inoculum in 5 minutes . Activity on Mycobacterium showed great differences between 2% glutaraldehyde and the rest of products (> 5 log versus < 3 log reduction in 20 minutes), with an exception: NDP-alc, with similar and faster activity (> 5 log in 5 minutes) than 2% glutaraldehyde . With human blood, the survival microorganisms increase 0.3 log (average) in all the disinfectants used . The aggressiveness on metallic devices was greater in Virkon than in the other disinfectants . We conclude that NDP (alone or in alcoholic solution) may be a good alternative to glutaraldehyde in hospital instruments disinfection.

Insect Mol Biol, 2000 Feb, 9(1), 75 - 84
Cloning and analysis of a cecropin gene from the malaria vector mosquito, Anopheles gambiae; Vizioli J et al.; Parasites of the genus Plasmodium are transmitted to mammalian hosts by anopheline mosquitoes . Within the insect vector, parasite growth and development are potentially limited by antimicrobial defence molecules . Here, we describe the isolation of cDNA and genomic clones encoding a cecropin antibacterial peptide from the malaria vector mosquito Anopheles gambiae . The locus was mapped to polytene division 1C of the X chromosome . Cecropin RNA was induced by infection with bacteria and Plasmodium . RNA levels varied in different body parts of the adult mosquito . During development, cecropin expression was limited to the early pupal stage . The peptide was purified from both adult mosquitoes and cell culture supernatants . Anopheles gambiae synthetic cecropins displayed activity against Gram-negative and Gram-positive bacteria, filamentous fungi and yeasts.

Helicobacter, 2000 Mar, 5(1), 22 - 3
Helicobacter pylori culture from a positive, liquid-based urease test for routine clinical use: a cost-effective approach; Jaup BH et al.; BACKGROUND: The aim of our study was to test the feasibility of culturing Helicobacter pylori directly from biopsies aimed for rapid urease test in routine clinical practice . MATERIALS AND METHODS: In 260 consecutive patients referred for gastroscopy because of dyspepsia one antral biopsy was routinely used for our "in house" rapid urease test (RUT) . Positive biopsies were placed in a transport medium and sent to the laboratory . The biopsies were cultured and incubated at 37 degrees C for 5-7 days . H . pylori was identified and routinely tested for antimicrobial resistance by using the E-test . RESULTS: In 118 out of 260 patients (45%) the urease test turned positive and the growth of H . pylori was sufficient to allow testing of antimicrobial resistance . CONCLUSION: H . pylori could be cultured from almost all positive RUT specimens . A liquid RUT is thus more suitable for culture, saving additional biopsies.

Chemotherapy, 2000 Mar-Apr, 46(2), 150 - 2
Adequate levofloxacin treatment schedules for uterine cervicitis caused by Chlamydia trachomatis; Mikamo H et al.; The in vivo efficacy of levofloxacin (LVFX), one of the most standard new quinolone antimicrobial agents, in the different treatment schedules of Chlamydia trachomatis uterine cervicitis in women was evaluated . Cervical C . trachomatis was detected by polymerase chain reaction . LVFX at a dosage of 300 mg t.i.d . for 5, 7 and 14 days was orally administered to 18, 33 and 35 Japanese patients, respectively . The eradication rate and the recurrence rate in the different treatment schedules of C . trachomatis were evaluated . The eradication rate in 5-, 7- or 14-day cases was 44.4, 87.9 or 88.6%, respectively . The recurrence rate of 5-, 7- or 14-day cases was 50.0, 0 or 0%, respectively . Seven-day treatment with LVFX is adequate for and effective in C . trachomatis uterine cervicitis .

Life Sci, 2000, 66(5), PL 77 - 82
Grepafloxacin inhibits tumor necrosis factor-alpha-induced interleukin-8 expression in human airway epithelial cells; Hashimoto S et al.; We examined the effect of grepafloxacin (GPFX), a new fluoroquinolone antimicrobial agent, on interleukin-8 (IL-8) expression in tumor necrosis factor-alpha (TNF-alpha)-stimulated human airway epithelial cells (AEC) . GPFX inhibited IL-8 protein production as well as mRNA expression in a concentration-dependent manner (2.5 - 25 micro g/ml), but the inhibition of IL-8 expression by corresponding concentrations of GPFX to serum and airway lining fluids was not complete . We discuss the modulatory effect of GPFX on IL-8 production in the context of its efficacy on controlling chronic airway inflammatory diseases.

Thorac Cardiovasc Surg, 1999 Dec, 47(6), 405 - 10
Current practice of peri- and postoperative antibiotic therapy in cardiac surgery in Germany . Working Group on Cardiothoracic Surgical Intensive Care Medicine of the German Society for Thoracic and Cardiovascular Surgery; Markewitz A et al.; BACKGROUND: The increasing development of antimicrobial resistance of common bacterial pathogens presents one of the most significant challenges to clinical medicine, particularly intensive care medicine . One factor which has contributed to this development is the (over)use of antibiotic treatment . Therefore the objective of this study was to scrutinize the current practice of empiric antibiotic therapy in cardiac surgery in Germany for 1) perioperative prophylaxis and 2) postoperative therapy prior to the availability of susceptibility patterns for the infecting pathogen . METHODS: A questionnaire was sent to all centers performing cardiac surgery in Germany . Questions referred to drugs used as well as dosage, homogeneity and duration of antibiotic prophylaxis, time and/or reason for changing this regimen, drugs used for first-, second-, and third-line empiric postoperative antibiotic treatment, and homogeneity of antibiotic usage . RESULTS: All but 3 institutions (96.3%) answered . 1 . Perioperative prophylaxis: All but 4 centers (94%) use first- (n = 32 = 43%) or second-generation cephalosporins (n = 38 = 51%) most commonly for 24 hours (n = 60 = 81%) . Prophylaxis never exceeds 3 days . 74% of all institutions (n = 55) use the same antimicrobial agent for all cardiac procedures performed, while 26% (n = 19) change their regimen in selected patient groups, most commonly for heart transplantation . The entire prophylaxis is changed mainly according to susceptibility patterns (n = 63 = 85%), 7 centers (10%) change according to a fixed time schedule, while 4 institutions (5%) never change the antimicrobial drug . 2 . Empiric postoperative therapy: A total of 29 different antibiotics out of 8 subclasses are used . No major differences between 1st-, 2nd-, and 3rd-line therapy could be detected, with the exception of a decreasing usage of beta-lactams (carbapenems excluded) from 60% in 1st-line to 23% in 3rd-line therapy and an increasing usage of glycopeptides from 5% in 1st-line to 18% in 3rd-line therapy . 41 institutions (55%) use the same antibiotic regimen on the intensive care unit and the normal ward, 9 centers (12%) use the same drug for perioperative prophylaxis and postoperative therapy, and 12 institutions (16%) prescribe a combination therapy . CONCLUSIONS: Perioperative prophylaxis in cardiac surgery in Germany is performed on a relatively uniform basis and at low cost . The heterogeneity of antibiotic regimens for postoperative therapy may indicate the need for recommendations and/or guidelines for this type of treatment . The indications for the usage of reserve antibiotics, e.g . vancomycin, implying the possible risk of creating pathogens with untreatable resistance patterns, as well as strategies aimed at preventing the development of resistance should be the subject of further discussions.

J Microbiol Methods, 2000 Feb, 39(3), 189 - 96
An enzyme-release assay for the assessment of the lytic activities of complement or antimicrobial peptides on extracellular Toxoplasma gondii; Seeber F; A method is described which allows the evaluation of the membrane lytic activity of either complement or antimicrobial peptides against the extracellular stage of the human protozoan parasite Toxoplasma gondii . The assay is based on lacZ transgenic parasites, determining the activity of released cytoplasmic beta-galactosidase into the culture supernatant upon membrane disintegration . This method was used to evaluate the lytic activities of (i) complement which is a natural defense mechanism in infected hosts against extracellular parasites, and (ii) antimicrobial peptides which have not been evaluated against T . gondii before . The results show that the assay provides a simple and convenient way to assess the membrane lytic activity of such compounds and that T . gondii, like other protozoan parasites, is vulnerable to the membrane-lytic effect of antimicrobial peptides.

Chest, 2000 Feb, 117(2), 494 - 502
Etiology and microbial patterns of pulmonary infiltrates in patients with orthotopic liver transplantation; Torres A et al.; STUDY OBJECTIVE: To evaluate the etiology and microbial patterns of pulmonary infiltrates in liver transplant patients using a bronchoscopic diagnostic approach and the impact of diagnostic results on antimicrobial treatment decisions . DESIGN: A prospective cohort study . SETTING: A 1,000-bed tertiary-care university hospital . Patients and methods: Fifty consecutive liver transplant patients with 60 episodes of pulmonary infiltrates (33 episodes during mechanical ventilation) were studied using flexible bronchoscopy with protected specimen brush (PSB) and BAL . RESULTS: A definite infectious etiology was confirmed in 29 episodes (48%) . Eighteen episodes corresponded to probable pneumonia (30%), 10 episodes had noninfectious etiologies (17%), and 3 remained undetermined (5%) . Opportunistic infections were the most frequent etiology (16/29, 55%, including 1 mixed etiology) . Bacterial infections (mainly Gram-negative) accounted for 14 of 29 episodes (48%), including 1 of mixed etiology . The majority of bacterial pneumonia episodes (n = 10, 71%) occurred in period 1 (1 to 28 days posttransplant) during mechanical ventilation, whereas opportunistic episodes were predominant in periods 2 and 3 (29 to 180 days and > 180 days posttransplant, respectively; n = 14, 82%) . Microbial treatment was changed according to diagnostic results in 21 episodes (35%) . CONCLUSIONS: Microbial patterns in liver transplant patients with pulmonary infiltrates corresponded to nosocomial, mainly Gram-negative bacterial pneumonia in period 1, and to opportunistic infections in period 2 and, to a lesser extent, period 3 . A comprehensive diagnostic evaluation including PSB and BAL fluid examination frequently guided specific antimicrobial therapy.

J Infect Dis, 2000 Feb, 181(2), 779 - 82
Characterization of enterotoxigenic Escherichia coli strains in patients with travelers' diarrhea acquired in Guadalajara, Mexico, 1992-1997; Jiang ZD et al.; The relationship between enterotoxigenic Escherichia coli (ETEC) and travelers' diarrhea was examined in a high-risk area in 1992-1997 . Toxin patterns, colonization-factor antigens (CFAs), and in vitro antimicrobial susceptibility were determined . In total, 928 US students with diarrhea acquired in Guadalajara, Mexico, were screened for enteric pathogens . Diagnosis of ETEC infection was done with oligonucleotide probes . ETEC was isolated in 19.9% of the travelers with diarrhea . CFAs were identified in 51% of the ETEC strains . The highest CFA frequency was observed among heat-stable isolates . Ampicillin, furazolidone, and sulfisoxazole resistance of ETEC increased during the study period . ETEC isolation rates and CFA patterns varied little during the 6 years of the study, which has implications for immunoprophylactic strategies . The finding that differences in the results of ribotyping and plasmid analysis change over time suggests that multiple strains of ETEC were responsible for the illness in the region studied.

Toxicon, 2000 Mar, 38(3), 373 - 80
Characterisation of antibacterial activity of peptides isolated from the venom of the spider Cupiennius salei (Araneae: Ctenidae); Haeberli S et al.; The characterisation of the antimicrobial activity of five antibacterial peptides, isolated from the venom of the neotropical wandering spider Cupiennius salei is reported here . The peptides have a molecular mass, determined by electrospray ionisation-mass spectrometry, between 3-4 kDa . Minimal inhibitory concentrations against five different bacteria species were determined by a liquid growth inhibition assay . All five peptides showed minimal inhibitory concentrations that are comparable to those of other known antibacterial peptides, like insect defensins and cecropins, found in the last years in a large diversity of animals . The peptides are supposed to lyse the cells by formation of either distinct channels or pores, but their mode of action is not yet revealed.

Farmaco, 1999 Nov-Dec, 54(11-12), 800 - 9
Sterically controlled regiospecific heterocyclization of 3-hydrazino-5-methyl-1,2,4-triazino{5,6-b}indole to 10-methyl-1,2,4-triazolo{4',3':2,3{1,2,4-triazino{5,6-b}indoles; Shaban MA et al.; 3-Hydrazino-5-methyl-1,2,4-triazino{5,6-b}indole underwent sterically controlled regiospecific heterocyclizations with a variety of one-carbon cyclizing agents to give the sterically more favored linearly annulated 10-methyl-1,2,4-triazolo{4',3':2,3{1,2,4-triazino{5,6-b}indoles rather than the sterically less favored angularly annulated 10-methyl-1,2,4-triazolo{3',4':3,4}1,2,4-triazino{5,6-b}indoles . The assigned structures were corroborated by comparison with unequivocally synthesized authentics, chemical and spectral data . The antimicrobial activity of some of the prepared compounds was investigated.

J Pept Res, 2000 Jan, 55(1), 51 - 62
Relationship between the tertiary structures of mastoparan B and its analogs and their lytic activities studied by NMR spectroscopy; Yu K et al.; Mastoparan B (MP-B), an antimicrobial cationic tetradecapeptide amide isolated from the venom of the hornet Vespa basalis, is an amphiphilic alpha-helical peptide . MP-B possesses a variety of biological activities, such as mast cells degradation histamine release, erythrocyte lysis and inhibition of the growth of gram-positive and gram-negative bacteria . In order to study the relationship between the structure and the biological activity of MP-B, we used four analogs by replacing amino acids with alanine . Tertiary structures of MP-B and its analogs in 2,2,2-trifluoroethanol (TFE)-containing aqueous solution have been determined by NMR spectroscopy and molecular modeling . The results indicate that {Ala4}MP-B and {Ala12}MP-B with higher hydrophobicity adopt a higher content of amphiphilic helical structures, and have better antimicrobial and hemolytic activities than MP-B . However, {Ala3}MP-B and {Ala9}MP-B with lower hydrophobicity have disordered structures . {Ala3}MP-B and {Ala9}MP-B have low antimicrobial activity and much less hemolytic activity relative to MP-B . It is likely that tryptophan residue in MP-B and appropriate hydrophobicity of MP-B to induce alpha-helical structure is essential for the antibacterial and hemolytic activity of MP-B . This study can aid understanding of the structure-activity relationship of MP-B and to design peptides to possess lytic activity.

JAMA, 2000 Feb 2, 283(5), 609 - 16
Long-term outcomes of persons with Lyme disease; Seltzer EG et al.; CONTEXT: Few data exist about the long-term outcomes of patients with Lyme disease . OBJECTIVE: To assess the long-term outcomes of patients with Lyme disease . DESIGN: Two-part project including a community-based longitudinal cohort study and a matched cohort study . SETTING AND PARTICIPANTS: Six hundred seventy-eight patients identified from a random sample of all reports of Connecticut residents with suspected Lyme disease submitted to the Connecticut Department of Public Health from 1984-1991 were evaluated in the longitudinal study; for a random subsample of 212 patients from the larger study, 212 age-matched controls without Lyme disease also were enrolled . MAIN OUTCOME MEASURES: Self-reports or parents' reports of symptoms and ability to perform certain daily activities since diagnosis of Lyme disease; scores on the 36-Item Short-Form Health Survey and the Center for Epidemiologic Studies-Depression scale, for adults, by case-definition status and between patients and controls . RESULTS: Of the 678 patients, 51.6% were female, 34.4% were children, and 64.3% met the national surveillance case definition for Lyme disease . Most patients (85.6%) were treated with antimicrobial agents . Interviews were conducted a median of 51 months after diagnosis (range, 15-135 months) . An increased frequency of symptoms (eg, pain, fatigue) or of difficulty with daily activities (eg, performing housework, exercising) was reported by 69% of the patients, although few (19%) of these problems were attributed to Lyme disease . Whenever there was a statistically significant difference in the frequencies of either increased symptoms or increased difficulties with typical activities between those who did or did not meet the surveillance case definition, in all instances the greater frequency of problems was in the group that did not meet the case definition . The frequencies of reports of both increased symptoms and increased difficulties with typical activities among patients who had been diagnosed as having Lyme disease were similar to those among age-matched controls without Lyme disease . CONCLUSIONS: In this cohort, although many patients reported increases in symptoms and/or increased difficulties with typical daily activities between 1 and 11 years after diagnosis of Lyme disease, the frequencies of these reports were similar to the frequencies of such reports among age-matched controls without Lyme disease.

Lett Appl Microbiol, 1999 Nov, 29(5), 323 - 6
The intrinsic resistance of Escherichia coli to various antimicrobial agents requires ppGpp and sigma s; Greenway DL et al.; We have examined the effect of a wide range of antimicrobial compounds (antibiotics and biocides) on the growth of various strains of Escherichia coli which vary in their ability to produce ppGpp and sigma s . We conclude that strains able to synthesize ppGpp, either in a RelA- or SpoT-dependent manner, possess a greater resistance to antimicrobial compounds compared with strains that cannot produce ppGpp . Investigation of an E . coli strain, unable to produce sigma s, and an isogenic parent strain, suggests that there is a requirement for this sigma factor in increased expression of intrinsic resistance . We propose that ppGpp is required to induce production of sigma s, which in turn directs gene expression of intrinsic resistance determinants.

Eur Arch Otorhinolaryngol, 2000, 257(1), 1 - 5
Lateral sinus thrombosis after untreated otitis media . A clinical problem--again?
Spandow O, Gothefors L, Fagerlund M, Kristensen B, Holm S.
Antimicrobial agents have greatly reduced the incidence of intracranial complications of infections of the middle ear and mastoid . Too many prescriptions and overconsumption of antibiotics when otitis media is suspected has caused resistance to many antibiotics, leading to a pronounced and justifiable desire to reduce the widespread excessive use of antibiotics . The possible untoward consequences of a too restricted antibiotic policy, however, is illustrated by the following case of a 14-year-old boy who, after non-treatment of an ear infection, fell ill with one-sided headache and vomiting caused by a lateral sinus thrombosis . After intravenous treatment with antibiotics, anticoagulants and ventilation of the middle ear, the infection was cured without complications . This case calls attention to the symptoms of otitic complications arising outside the temporal bone . The physician must always bear in mind the possibility of an unusual event . The general treatment of endocranial complications is outlined, giving details of the treatment given in this special case . We stress that one should not be too cautious in prescribing antibiotics in otitis media.

Eur Biophys J, 2000, 28(8), 683 - 8
Grazing incidence X-ray diffraction of highly aligned phospholipid membranes containing the antimicrobial peptide magainin 2; Munster C et al.; We present the first study of grazing incidence X-ray diffraction on a model system of phospholipid membranes and antimicrobial peptides . For this purpose, highly oriented multilamellar samples have been prepared on solid substrates . By this technique, the short-range order of the lipid chains in the fluid L(alpha) phase can be investigated quantitatively, including not only the mean distance between acyl chains, but also the associated correlation length . The short-range order in lecithin is found to be severely affected by the amphiphilic peptide magainin 2.

Neuroradiology, 2000 Jan, 42(1), 14 - 8
MRI of intracranial toxoplasmosis after bone marrow transplantation; Dietrich U et al.; Toxoplasma encephalitis was confirmed by biopsy in three patients with bone marrow (BMT) or peripheral blood stem-cell transplantation (PBSCT) . All had MRI before antimicrobial therapy . The intensity of contrast enhancement was very variable . One patient had one large, moderately enhancing cerebral lesion and several smaller almost nonenhancing lesions . The second had small nodular and haemorrhagic lesions without any enhancement . The third had late cerebral toxoplasmosis and showed multiple lesions with marked contrast enhancement . The moderate or absent contrast enhancement in the two patients in the early phase of cerebral toxoplasmosis may be related to a poor immunological response, with a low white blood cell count in at least one patient . Both received higher doses of prednisone than the patient with late infection, leading to a reduced inflammatory response . In patients with a low leukocyte count and/or high doses of immunosuppressive therapy, typical contrast enhancement may be absent.

J Hosp Infect, 2000 Feb, 44(2), 141 - 5
Measurement of ultrasonic-induced chlorhexidine liberation: correlation of the activity of chlorhexidine-silver-sulfadiazine-impregnated catheters to agar roll technique and broth culture; Schierholz JM et al.; The diagnosis of intravascular catheter-related infections continues to be a challenge to both the clinician and the microbiologist . To assess the antiseptic effects of silver-sulfadiazine-chlorhexidine-impregnated central venous catheters (SSC) on catheter culture systems, segments of fresh antiseptic- and non antiseptic-impregnated catheters as well as extracted catheters following five days of immersion in PBS were sonicated . The chlorhexidine liberated from the catheter material by ultrasonication was measured by HPLC . Fresh antiseptic-impregnated catheter segments rolled on seeded agar plates produced inhibition zones unlike catheters which had been extracted for >five days in phosphate buffered saline (PBS) . Scanning electron microscopy (SEM) revealed that chlorhexidine-silversulfadiazine crystals were located in the superficial catheter matrix . Direct contact of superficially located drug particles with seeded agar plates probably caused the inhibition of bacterial growth . The study suggests that antiseptic compounds readily elute from fresh catheters during solid medium-based culturing processes and ultrasonication . The addition of inhibitors of silversulfadiazine-chlorhexidine to media may be prudent especially when culturing antimicrobial loaded catheters removed after short inwelling times .

Liver, 1999 Dec, 19(6), 495 - 500
Visualization of oxygen radical production in mouse liver in response to infection with Schistosoma mansoni; Abdallahi OM et al.; BACKGROUND/AIMS: The tropical parasite S . mansoni induces granulomatous inflammation in the liver, following the lodging of eggs in this organ . In vitro studies suggested that the host's response might involve the production of oxygen radicals . METHODS: In an attempt to investigate the situation at the site of inflammation, under disease conditions, livers of infected mice were treated with dichlorodihydrofluorescein diacetate which fluoresces after oxidation . RESULTS: Fluorescence of the oxidized tracer revealed that oxygen radicals were produced by granulomatous inflammatory cells . The phenomenon reached its highest intensity close to the eggs . The membranes of the cells were strongly labelled, probably reflecting membrane-associated NADPH oxidase activity . The cytoplasm of hepatocytes was also fluorescent but with lower intensity; hepatocyte membranes or nuclei were not labelled . Fluorescence was reduced drastically by treatment with catalase and antioxidants, indicating the occurrence of H2O2 . Treatment with superoxide dismutase had no effect . Neither the livers of uninfected animals nor those of infected animals before parasite egg deposition were labelled . Eosinophil peroxidase activity was released in the areas of inflammatory cells, but was not found in hepatocytes . CONCLUSIONS: The H2O2/peroxidase system, which is the cornerstone of the antimicrobial defense associated with inflammation, is activated in close contact with parasite eggs . The process does contribute to egg killing in vivo . Moreover, hepatocytes undergo oxidative stress in the entire organ . This finding is in agreement with the parasite-induced decrease of liver antioxidant defenses demonstrated previously.

J Biol Chem, 2000 Feb 11, 275(6), 4230 - 8
Structure-activity relationship study of antimicrobial dermaseptin S4 showing the consequences of peptide oligomerization on selective cytotoxicity; Feder R et al.; To understand how peptide organization in aqueous solution might affect the activity of antimicrobial peptides, the potency of various dermaseptin S4 analogs was assessed against human red blood cells (RBC), protozoa, and several Gram-negative bacteria . Dermaseptin S4 had weak antibacterial activity but potent hemolytic or antiprotozoan effects . K(4)K(20)-S4 was 2-3-fold more potent against protozoa and RBC, yet K(4)K(20)-S4 was more potent by 2 orders of magnitude against bacteria . K(4)-S4 had similar behavior as K(4)K(20)-S4, but K(20)-S4 and analogous negative charge substitutions were as active as dermaseptin S4 or had reduced activity . Binding experiments suggested that potency enhancement was not the result of increased affinity to target cells . In contrast, potency correlated well with aggregation properties . Fluorescence studies indicated that K(20)-S4 and all negative charge substitutions were as aggregated as dermaseptin S4, whereas K(4)-S4 and K(4)K(20)-S4 were clearly less aggregated . Overall, the data indicated that N-terminal domain interaction between dermaseptin S4 monomers is responsible for the peptide's oligomerization in solution and, hence, for its limited spectrum of action . Moreover, bell-shaped dose-response profiles obtained with bacteria but not with protozoa or RBC implied that aggregation can have dramatic consequences on antibacterial activity . Based on these results, we tested the feasibility of selectivity reversal in the activity of dermaseptin S4 . Tampering with the composition of the hydrophobic domains by reducing hydrophobicity or by increasing the net positive charge affected dramatically the peptide's activity and resulted in various analogs that displayed potent antibacterial activity but reduced hemolytic activity . Among these, maximal antibacterial activity was displayed by a 15-mer version that was more potent by 2 orders of magnitude compared with native dermaseptin S4 . These results emphasize the notion that peptide-based antibiotics represent a highly modular synthetic antimicrobial system and provide indications of how the peptide's physico-chemical properties affect potency and selectivity.

J Antimicrob Chemother, 2000 Feb, 45(2), 231 - 3
In vitro activity of ciprofloxacin, sparfloxacin, ofloxacin, amikacin and rifampicin against Ghanaian isolates of Mycobacterium ulcerans; Thangaraj HS et al.; MICs of ciprofloxacin, sparfloxacin, ofloxacin, amikacin and rifampicin were determined for 14 primary clinical isolates and three reference isolates of Mycobacterium ulcerans by modifying a standard agar dilution method for testing Mycobacterium tuberculosis sensitivity . All these antimicrobials were active against every isolate of M . ulcerans . Sparfloxacin exhibited the highest activity and ofloxacin was the least effective . Rifampicin exhibited the broadest range of activity.

J Antimicrob Chemother, 2000 Feb, 45(2), 221 - 4
Antibacterial activity of antibiotic-soaked polyvinylpyrrolidone-grafted silicon elastomer hydrocephalus shunts; Boelens JJ et al.; If shunts, inserted for the relief of hydrocephalus, are pretreated with antimicrobials, the incidence of shunt-associated infections (SAI) may be reduced . The duration of the antibacterial activity of shunts, made from conventional silicon elastomer (SE) or from SE grafted with the hydrogel polyvinylpyrrolidone (SEpvp), which had been soaked in various antibiotics, was assessed in vitro . For any antibiotic or combination, using an arbitrary breakpoint (aBP), SEpvp remained antibacterially active for longer periods than SE . Bacterial adherence to either shunt was prevented during the period of antibacterial activity . Thus, the aBP is a good indicator of the capacity of antimicrobial-treated shunts to prevent bacterial colonization in vitro . Hydrogel-grafting of shunts may be useful in preventing SAI.

J Antimicrob Chemother, 2000 Feb, 45(2), 175 - 82
Long-term trends in susceptibility of Moraxella catarrhalis: a population analysis; Walker ES et al.; A retrospective, population analysis of antimicrobial susceptibility patterns was performed on Moraxella catarrhalis isolates recovered from a single medical centre to detect temporal trends and infer potential mechanisms of reduced susceptibility . The duration of this study, June 1984 to July 1994, encompassed the period during which the frequency of beta-lactamase production expanded from 30 to 96% in the population . MICs of penicillin G, cefamandole, ceftriaxone, amoxycillin/clavulanate, imipenem, clarithromycin, tetracycline, ciprofloxacin and trimethoprim/sulphamethoxazole for a representative sample of 375 isolates were determined . Analyses were conducted to test for variation in susceptibility among isolates, correlations of susceptibility levels among different antimicrobial agents, and temporal patterns in susceptibility . All antimicrobials except clarithromycin displayed significant differences among isolates within years, and mean MICs of all antimicrobial agents except tetracycline and clarithromycin varied significantly between years . Temporal trends to a reduction in susceptibility were detected to four of five beta-lactam antimicrobials (all except cefamandole) . Significant correlations in MICs were uncovered among all pairs of four beta-lactam antimicrobials in both producers and non-producers of beta-lactamase . In contrast, cefamandole MICs were correlated only with ceftriaxone and penicillin, and these were limited to beta-lactam producing isolates; cefamandole and amoxycillin/clavulanate showed a correlation limited to non-producing isolates . For some antimicrobials, trends toward decreasing susceptibility may have been caused by an increased proportion of beta-lactamase producing isolates in the population, but the observation of significant decreases in susceptibility limited to beta-lactamase-producing isolates suggests that the underlying factors were different forms of beta-lactamase, beta-lactamase-dependent modifiers and/or additional factors.

Adv Exp Med Biol, 1999, 473, 31 - 45
Interference with virus and bacteria replication by the tissue specific expression of antibodies and interfering molecules; Enjuanes L et al.; Historically, protection against virus infections has relied on the use of vaccines, but the induction of an immune response requires several days and in certain situations, like in newborn animals that may be infected at birth and die in a few days, there is not sufficient time to elicit a protective immune response . Immediate protection in new born could be provided either by vectors that express virus-interfering molecules in a tissue specific form, or by the production of animals expressing resistance to virus replication . The mucosal surface is the largest body surface susceptible to virus infection that can serve for virus entry . Then, it is of high interest to develop strategies to prevent infections of these areas . Virus growth can be interfered intracellularly, extracellularly or both . The antibodies neutralize virus intra- and extracellularly and their molecular biology is well known . In addition, antibodies efficiently neutralize viruses in the mucosal areas . The autonomy of antibody molecules in virus neutralization makes them functional in cells different from those that produce the antibodies and in the extracellular medium . These properties have identified antibodies as very useful molecules to be expressed by vectors or in transgenic animals to provide resistance to virus infection . A similar role could be played by antimicrobial peptides in the case of bacteria . Intracellular interference with virus growth (intracellular immunity) can be mediated by molecules of very different nature: (i) full length or single chain antibodies; (ii) mutant viral proteins that strongly interfere with the replication of the wild type virus (dominant-negative mutants); (iii) antisense RNA and ribozyme sequences; and (iv) the product of antiviral genes such as the Mx proteins . All these molecules inhibiting virus replication may be used to obtain transgenic animals with resistance to viral infection built in their genomes . We have developed two strategies to target into mucosal areas either antibodies to provide immediate protection, or antigens to elicit immune responses in the enteric or respiratory surfaces in order to prevent virus infection . One strategy is based on the development of expression vectors using coronavirus derived defective RNA minigenomes, and the other relies on the development of transgenic animals providing virus neutralizing antibodies in the milk during lactation . Two types of expression vectors are being engineered based on transmissible gastroenteritis coronavirus (TGEV) defective minigenomes . The first one is a helper virus dependent expression system and the second is based on self-replicating RNAs including the information required to encode the TGEV replicase . The minigenomes expressing the heterologous gene have been improved by using a two-step amplification system based on cytomegalovirus (CMV) and viral promoters . Expression levels around 5 micrograms per 10(6) cells were obtained . The engineered minigenomes will be useful to understand the mechanism of coronavirus replication and for the tissue specific expression of antigen, antibody or virus interfering molecules . To protect from viral infections of the enteric tract, transgenic animals secreting virus neutralizing recombinant antibodies in the milk during lactation have been developed . Neutralizing antibodies with isotypes IgG1 or IgA were produced in the milk with titers of 10(6) in RIA that reduced virus infectivity by one million-fold . The recombinant antibodies recognized a conserved epitope apparently essential for virus replication . Antibody expression levels were transgene transgene copy number independent and were related to the transgene integration site . This strategy may be of general use since it could be applied to protect newborn animals against infections of the enteric tract by viruses or bacteria for which a protective MAb has been identified . Alternatively, the same strategy could be used to target the expression of antibio

J Hosp Infect, 1999 Dec, 43(4), 255 - 64
Choosing disinfectants; Fraise AP; Disinfectant choice is an important part of the role of the infection control team . Its importance has increased due to concern over transmission of blood-borne viruses and the need to identify alternatives to gluteraldehyde . Factors to be taken into account when choosing disinfectants include compliance with COSHH regulations, user acceptability, instrument compatibility and antimicrobial activity . Compounds vary in their suitability for different uses and an agent's properties must be fully evaluated before adopting it for a particular purpose . This review outlines the main properties that need to be established and covers the major characteristics of main classes of disinfectants.

J Hosp Infect, 1999 Dec, 43 Suppl, S293 - 6
What does a clinician expect from a microbiologist? Towards an effective joint policy; Grosek S; What a clinician needs from a microbiologist and microbiological service depends on the specialty . To provide a diagnosis of infection, the service should organize and also follow-up the specimen transport, microbiological examination and antimicrobial susceptibility testing together with antigen detection and other modern test technology . A manual describing the local service and including guidelines should be placed in every department . At the same time a clinician should be familiar with clinical syndromes and causative micro-organisms, in order to be able to ask for the correct investigation . Only with continuous interchange of information by both parties is an effective joint policy possible in daily routine work.

J Hosp Infect, 1999 Dec, 43 Suppl, S261 - 4
Antibiotic policies and the role of strategic hospital leadership; Masterson RG; Operational aspects, programme construction and implementation are all essential components of antimicrobial control but are not the direct remit of management and must rest with the professional provider . Hospital leaders can influence antibiotic control through the priority they give it . This must not be purely financially driven and must incorporate an awareness of issues surrounding patient care . Such attitudes should encompass the consequences of poor prescribing practices in both human and corporate terms . A leader's recognition of these elements can be expressed through securing resources in terms of both the human and hardware components . The best signalling of the status of this activity is through ensuring its inclusion in clinical governance and organisational Board reports . The goals for hospital leaders should be evidence of effective working practices and the execution of their own responsibilities by championing robust structures and procedures are in place . Potent hospital leadership delivered to the focus of antimicrobial control programmes is a major tool for their success.

J Hosp Infect, 1999 Dec, 43 Suppl, S97 - 103
Nosocomial antimicrobial resistance surveillance; Cookson BD; The global threat of antimicrobial resistance and potentially untreatable infections is a serious matter under review currently by the WHO and many countries throughout the world . I consider the optimal surveillance scheme and point out the various biases in the systems that we have been using in the UK over the last decade . MRSA are used as an example where similar trends have been identified in these systems and the information has, once again, proved to be of value to the MRSA control working party.

Bioorg Med Chem, 1999 Dec, 7(12), 2985 - 90
Synthesis of novel unnatural amino acid as a building block and its incorporation into an antimicrobial peptide; Oh JE et al.; Considering the biological mechanism and in vivo stability of antimicrobial peptides, we designed and synthesized novel unnatural amino acids with more positively charged and bulky side chain group than lysine residue . The unusual amino acids, which were synthesized by either solution phase or solid phase, were incorporated into an antimicrobial peptide . Its effect on the stability, activity, and the structure of the peptide was studied to evaluate the potential of these novel unnatural amino acids as a building block for antimicrobial peptides . The incorporation of this unusual amino acid increased the resistance of the peptide against serum protease more than three times without a decrease in the activity . Circular dichroism spectra of the peptides indicated that all novel unnatural amino acids must have lower alpha helical forming propensities than lysine . Our results indicated that the unnatural amino acids synthesized in this study could be used not only as a novel building block for combinatorial libraries of antimicrobial peptides, but also for structure-activity relationship studies about antimicrobial peptides.

Pharm World Sci, 1999 Dec, 21(6), 272 - 4
Stability of buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9% sodium chloride solution; Jappinen A et al.; Combinations of opioids and adjuvant drug solutions are often used in clinical practice while little information is available on their microbiological or chemical stability . Currently there are no commercially available, prepacked, ready-to-use epidural or subcutaneous mixtures . Thus, epidural and subcutaneous analgesic mixtures must be prepared in the pharmacy on an as-needed basis . Such mixtures are typically used for the treatment of severe pain in cancer patients . The aim of this study was to investigate the microbiological and chemical stability of a buprenorphine, haloperidol and glycopyrrolate mixture in a 0.9% sodium chloride solution . A high performance liquid chromatographic (HPLC) method and pH-meter were used to conduct the analyses . Antimicrobial activity of each component was studied by an agar dilution method . According to the results from the chemical and microbiological stability studies, this mixture can be stored in polypropylene (PP) syringes and polyvinyl chloride (PVC) medication cassettes for at least 30 days at either 21 degrees C or 4 degrees C, and for 16 days in PP syringes at 36 degrees C, and for 9 days in PVC medication cassettes at 36 degrees C.

Nat Biotechnol, 2000 Feb, 18(2), 225 - 7
A colorimetric assay for rapid screening of antimicrobial peptides; Kolusheva S et al.; The increased resistance of various bacteria toward available antibiotic drugs has initiated intensive research efforts into identifying new sources of antimicrobial substances . Short antibiotic peptides (10-30 residues) are prevalent in nature as part of the intrinsic defense mechanisms of most organisms and have been proposed as a blueprint for the design of novel antimicrobial agents . Antimicrobial peptides are generally believed to kill bacteria through membrane permeabilization and extensive pore-formation . Assays providing rapid and easy evaluation of interactions between antimicrobial membrane peptides and lipid bilayers could significantly improve screening for substances with effective antibacterial properties, as well as contribute to the elucidation of structural and functional properties of antimicrobial peptides . Here we describe a colorimetric sensor in which particles composed of phospholipids and polymerized polydiacetylene (PDA) lipids were shown to exhibit striking color changes upon interactions with antimicrobial membrane peptides . The color changes in the system occur because of the structural perturbation of the lipids following their interactions with antimicrobial peptides . The assay was also sensitive to the antibacterial properties of structurally and functionally related peptide analogs.

Mol Plant Microbe Interact, 2000 Jan, 13(1), 54 - 61
Specific binding sites for an antifungal plant defensin from Dahlia (Dahlia merckii) on fungal cells are required for antifungal activity; Thevissen K et al.; Dm-AMP1, an antifungal plant defensin from seeds of dahlia (Dahlia merckii), was radioactively labeled with t-butoxycarbonyl-{35S}-L-methionine N-hydroxy-succinimi-dylester . This procedure yielded a 35S-labeled peptide with unaltered antifungal activity . {35S}Dm-AMP1 was used to assess binding on living cells of the filamentous fungus Neurospora crassa and the unicellular fungus Saccharomyces cerevisiae . Binding of {35S}Dm-AMP1 to fungal cells was saturable and could be competed for by preincubation with excess, unlabeled Dm-AMP1 as well as with Ah-AMP1 and Ct-AMP1, two plant defensins that are highly homologous to Dm-AMP1 . In contrast, binding could not be competed for by more distantly related plant defensins or structurally unrelated antimicrobial peptides . Binding of {35S}Dm-AMP1 to either N . crassa or S . cerevisiae cells was apparently irreversible . In addition, whole cells and microsomal membrane fractions from two independently obtained S . cerevisiae mutants selected for resistance to Dm-AMP1 exhibited severely reduced binding affinity for {35S}Dm-AMP1, compared with wild-type yeast . This finding suggests that binding of Dm-AMP1 to S . cerevisiae plasma membranes is required for antifungal activity of this protein.

J Antibiot (Tokyo), 1999 Nov, 52(11), 1023 - 8
Structures of flagranones A, B and C, cyclohexenoxide antibiotics from the nematode-trapping fungus Duddingtonia flagrans; Anderson MG et al.; Spectroscopic data define the structures of the flagranones A (2), B (3) and C (4) from the nematode-trapping fungus Duddingtonia flagrans . These antibiotics are structurally related to the farnesylated cyclohexenoxides of the oligosporon group recently isolated from the nematode-trapping fungus Arthrobotrys oligospora, and show similar antimicrobial activity.

Infect Control Hosp Epidemiol, 2000 Jan, 21(1), 12 - 7
The influence of the composition of the nursing staff on primary bloodstream infection rates in a surgical intensive care unit; Robert J et al.; OBJECTIVES: To determine the risk factors for acquisition of nosocomial primary bloodstream infections (BSIs), including the effect of nursing-staff levels, in surgical intensive care unit (SICU) patients . DESIGN: A nested case-control study . SETTING: A 20-bed SICU in a 1,000-bed inner-city public hospital . PATIENTS: 28 patients with BSI (case-patients) were compared to 99 randomly selected patients (controls) hospitalized > or =3 days in the same unit . RESULTS: Case- and control-patients were similar in age, severity of illness, and type of central venous catheter (CVC) used . Case-patients were significantly more likely than controls to be hospitalized during a 5-month period that had lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios than during an 8-month reference period; to be in the SICU for a longer period of time; to be mechanically ventilated longer; to receive more antimicrobials and total parenteral nutrition; to have more CVC days; or to die . Case-patients had significantly lower regular-nurse-to-patient and higher pool-nurse-to-patient ratios for the 3 days before BSI than controls . In multivariate analyses, admission during a period of higher pool-nurse-to-patient ratio (odds ratio {OR}=3.8), total parenteral nutrition (OR=1.3), and CVC days (OR=1.1) remained independent BSI risk factors . CONCLUSIONS: Our data suggest that, in addition to other factors, nurse staffing composition (ie, pool-nurse-to-patient ratio) may be related to primary BSI risk . Patterns in intensive care unit nurse staffing should be monitored to assess their impact on nosocomial infection rates . This may be particularly important in an era of cost containment and healthcare reform.

CLAO J, 2000 Jan, 26(1), 47 - 51
The diagnosis and management of Acanthamoeba keratitis; McCulley JP et al.; PURPOSE: The purpose of this study was to evaluate the immunology, pathogenesis and therapy of Acanthamoeba keratitis . METHODS: The recent development of an animal model of Acanthamoeba keratitis and its impact on the medical treatment and immunology of Acanthamoeba keratitis was reviewed . RESULTS: After initial reports, Acanthamoeba infection of the cornea remained a rare disease until an association with contact lens wear was first recognized . Although the disease is closely associated with contact lens wear, it appeared that the contaminated solutions that were coming into contact with the lenses caused the disease . All types of contact lenses can be associated with development of Acanthamoeba keratitis . Therefore, the contact lens serves as a carrier of Acanthamoeba to the surface of the eye . The typical patient with Acanthamoeba keratitis is a young healthy individual who is either a contact lens wearer or has had significant exposure to water contaminated with Acanthamoeba . There are several risk factors such as corneal trauma, contaminated solution and contact lenses that have been reported to be associated with Acanthamoeba keratitis . In spite of significant improvement in the diagnosis of Acanthamoeba keratitis, progress in developing and utilizing effective antimicrobial agents for treating this disease have been disappointing . A growing body of evidence suggests that the mammalian immune system, if properly activated, is capable of preventing and controlling ocular infections . CONCLUSIONS: In order to develop effective immunotherapeutic modalities, and to better understand the immune effector mechanisms that protect the cornea against Acanthamoeba infection, it is necessary to fully characterize and evaluate the immunobiology of Acanthamoeba keratitis.

Kansenshogaku Zasshi, 1999 Dec, 73(12), 1205 - 9
{Steroid pulse therapy and vital prognosis among pediatric cancer patients with sepsis}; Oda K et al.; The usefulness of glucocorticosteroid therapy in patients with sepsis has been controversial . We investigated the effect of steroid pulse therapy on the vital prognosis of pediatric patients with sepsis and followed the vital status up to one month after the use of pulse therapy . We reviewed the medical records of 89 pediatric cancer patients with sepsis treated at our hospital between 1988 and 1996 . The risks of potential predictors were estimated by calculating crude and adjusted relative risk (RR) . The total cumulative death was 33/89 (25%) . All patients treated with steroid pulse therapy died (12/12) . Patients with either interstitial pneumonia (IP), infection-associated hemophagocytic syndrome (IAHS) and graft-versus-host disease (GVHD) showed a significantly higher cumulative death (57% (12/21) vs 31% (21/68), p = 0.03) . Increased risk of cumulative death was suggested for the older age group, inappropriate antimicrobial therapy, and the conditions requiring steroid pulse therapy (IP, IAHS, and GVHD), (crude RR were 1.6, 1.6, and 1.9, respectively) . However, when adjusted for pulse therapy, these three factors no longer indicated risk elevation, (adjusted RR = 1.2, 1.2, and 0.3, respectively) . On the other hand, steroid pulse therapy per se was independently associated with increased risk of cumulative death (crude RR = 3.6, adjusted RR = 10) . Thus, the risk of the conditions requiring steroid pulse therapy (IP, IAHS, and GVHD) firstly observed could be regarded as an apparent association due to steroid pulse therapy.

J Clin Microbiol, 2000 Feb, 38(2), 872 - 3
Reliability of the MB/BacT system for testing susceptibility of Mycobacterium tuberculosis complex isolates to antituberculous drugs; Brunello F et al.; The susceptibility of 115 Mycobacterium tuberculosis complex clinical isolates to isoniazid, streptomycin, ethambutol, and rifampin was assessed by the MB/BacT and BACTEC 460TB systems . The correlation between the two tests was 98.3% for isoniazid, 100% for streptomycin and rifampin, and 95.8% for ethambutol . Turnaround times for antimicrobial susceptibility testing ranged from 5 to 11 days (median, 8.5 days) for MB/BacT and from 4 to 8 days (median, 6 days) for BACTEC 460TB.

J Clin Microbiol, 2000 Feb, 38(2), 789 - 94
Application of 16S rRNA gene sequencing to identify Bordetella hinzii as the causative agent of fatal septicemia; Kattar MM et al.; We report on the first case of fatal septicemia caused by Bordetella hinzii . The causative organism exhibited a biochemical profile identical to that of Bordetella avium with three commercial identification systems (API 20E, API 20 NE, and Vitek GNI+ card) . However, its cellular fatty acid profile was not typical for either B . avium or previously reported strains of B . hinzii . Presumptive identification of the patient's isolate was accomplished by traditional biochemical testing, and definitive identification was achieved by 16S rRNA gene sequence analysis . Phenotypic features useful in distinguishing B . hinzii from B . avium were production of alkali from malonate and resistance to several antimicrobial agents.

J Clin Microbiol, 2000 Feb, 38(2), 635 - 8
Serology of culture-confirmed cases of human granulocytic ehrlichiosis; Aguero-Rosenfeld ME et al.; We evaluated the antibody responses in the sera of 24 patients with culture-confirmed human granulocytic ehrlichiosis (HGE) . Antibody titers were measured by an indirect immunofluorescent-antibody assay (IFA) by using a local human isolate as the source of antigen . All patients received appropriate antimicrobial treatment . One hundred five serum specimens collected at baseline and at periodic intervals for up to 14 months were included in the study . Seroconversion was observed in 21 of 23 patients (91.3%) from whom convalescent-phase sera were obtained . Antibodies were first detected at an average of 11.5 days after onset of symptoms . Peak titers (>/=2,560 for 71.4% of patients and >/=640 for 95.2% of patients) were obtained an average of 14.7 days after onset of symptoms . Eleven of 13 patients (84.6%) from whom sera were collected between 6 and 10 months after onset of symptoms were still seropositive, and sera from 5 of 10 (50%) patients tested positive between 11 and 14 months after onset of symptoms . For a subset of 71 serum specimens from 17 patients with culture-confirmed HGE also tested by IFA by using either a human isolate from Wisconsin or an Ehrlichia equi isolate from a horse, there was qualitative agreement for 62 serum specimens (87 . 3%) . Peak titers were higher, however, with the local human HGE isolate, but the difference was not statistically significant . In summary, most patients with culture-confirmed HGE develop antibodies within 2 weeks of onset of symptoms . Antibodies reach high titers during the first month and remain detectable in about one-half of patients at 1 year after onset of symptoms.

Ostomy Wound Manage, 1999 Aug, 45(8), 23 - 7, 29-40; quiz 41-2
Infection in chronic wounds: controversies in diagnosis and treatment; Dow G et al.; Chronic wounds all have bacterial contamination, which will not impair healing . Wound contamination must be distinguished from wound colonization and infection . Bacterial infection in wounds depends on the number of organisms present, their virulence, and host resistance . The most important indicators of infection are both local and systemic host characteristics and a holistic assessment of the patient . Several specimen collection and culture techniques are available to measure bacterial burden in the chronic wound . Advantages and disadvantages of each one discussed along with a rational approach to systemic antibiotic therapy . The presence of foreign material such as skin grafts or skin substitutes may lower the bacterial burden that may impair healing from 1.0 x 10(6) colony-forming units to 1.0 x 10(5) or less . The benefits of wound debridement, wound irrigation, and local nonantibiotic modes of treatment have been proven but the use of topical antibiotics and antiseptics requires further assessment . More widespread use of multiple nonantibiotic modalities of treatment for infected chronic wounds and rational antibiotic prescribing should reduce the risk of future antimicrobial resistance such as MRSA.

Infect Control Hosp Epidemiol, 2000 Jan, 21(1 Suppl), S36 - 43
Strategies for study of the role of cycling on antimicrobial use and resistance; McGowan JE Jr; Resistant bacteria usually are seen first in the intensive care unit and other acute-care areas . Thus, strategies to control these organisms often are first tested in these healthcare settings . Frequent among these strategies are attempts to improve antimicrobial use . One proposed method to decrease resistance in special settings like the intensive care unit is the cycling or rotation of antimicrobials . This intervention must be evaluated in the context of other concomitant attempts to improve antimicrobial usage and must take into account other factors influencing resistance . Until such studies are done, the value of cycling and other efforts to limit prescribers' choices of drugs in endemic settings will be unclear . Studies to evaluate cycling will have to be of large scale to produce useful data . It is unlikely that many hospitals or healthcare systems will have sufficient resources on their own to develop studies of sufficient power to be applied widely . Thus, cooperative studies to provide data on this important issue should be an international priority.

Infect Control Hosp Epidemiol, 2000 Jan, 21(1 Suppl), S32 - 5
Antibiotic cycling and marketing into the 21st century: a perspective from the pharmaceutical industry; Lavin BS; Before the development of the first antimicrobial agents, bacteria already had demonstrated an ability to adapt to stress in the environment, resulting in the development of resistance that often makes the prevailing antibiotic treatment ineffective . The response to antimicrobial resistance in the medical community has been to use new or alternative antibiotics not previously used against the resistant bacteria . The pharmaceutical industry has responded to the resistance problem by producing newer antibiotics, either as modifications of currently existing compounds or as combinations of compounds that may inhibit or bypass the bacterial resistance mechanisms . The development of new antibiotics is a lengthy and costly process . To be successful, the pharmaceutical industry must anticipate the changing needs of the medical community, as well as the dynamic process of antimicrobial resistance . The marketing of new antimicrobial agents must be adaptable to the potential environmental pressures that induce bacterial resistance in order to ensure the longevity of the agents.

Infect Control Hosp Epidemiol, 2000 Jan, 21(1 Suppl), S22 - 31
The microbial genetics of antibiotic cycling; John JF Jr et al.; Cycling of currently available antibiotics to reduce resistance is an attractive concept . For cycling strategies to be successful, their implementation must have a demonstrable impact on the prevalence of resistance determinants already dispersed throughout the hospital and associated healthcare facilities . While antibiotic use in hospitals clearly constitutes a stimulus for the emergence of resistance, it is by no means the only important factor . The incorporation of resistance determinants into potentially stable genetic structures, including bacteriophages, plasmids, transposons, and the more newly discovered movable elements termed integrons and gene cassettes, forces some degree of skepticism about the potential for such strategies in institutions where resistance determinants are already prevalent . In particular, the expanding role of integrons may pose an ultimate threat to formulary manipulations such as cycling . Despite these concerns, the crisis posed by antimicrobial resistance warrants investigation of any strategy with the potential for reducing the prevalence of resistance . Over the next decade, new studies with carefully designed outcomes should determine the utility of antibiotic cycling as one control measure for nosocomial resistance.

Transplantation, 2000 Jan 15, 69(1), 70 - 5
Thrombocytopenia in liver transplant recipients: predictors, impact on fungal infections, and role of endogenous thrombopoietin; Chang FY et al.; BACKGROUND: Thrombocytopenia is a frequent and potentially serious complication in liver transplant recipients . The role of endogenous thrombopoietin level in posttransplant thrombocytopenia, has not been fully defined in liver transplant recipients . Additionally, there is accumulating evidence to suggest that platelets play a important role in antimicrobial host defense . METHODS: There were 50 consecutive liver transplant recipients studied . Variables predictive of thrombocytopenia, its impact on infectious morbidity and outcome, and serial thrombopoietin (TPO) serum concentration were assessed . RESULTS: The median pretransplant platelet count was 67 x 10(3)/cmm . After the liver transplantation, the median nadir platelet count was 33 x 10(3)/cmm and was reached a mean of 6 days after the transplant . A lower pretransplant platelet count (r= +.068, P=.0001), lower serum albumin before the transplants (r=+0.39, P=.014), longer operation time (r=0.27, P=.05), higher intraoperative packed red cells (r=0.28, P=.049) and fresh frozen plasma transfusions (r=0.42, P=.004), higher bilirubin at Day 7 (r=-.386, P=.005), and higher serum creatinine at Day 7 after the transplants (r=-.031, P=.025) correlated significantly with a lower nadir in platelets after the transplant . Nadir in platelet count was significantly lower in nonsurvivors compared with survivors (16 vs . 36 x 10(3)/cmm, P=.0001) . Forty-three percent (9 of 21) of the patients with nadir platelet counts of < or =30 x 10(3)/cmm had a major infection within 30 days of the transplant compared with 17% (5 of 29) with nadir platelet counts > 30 x 10(3)/cmm (P=.04) . Fungal infections occurred in 14% of the patients with nadir platelet counts of < or =30 x 10(3)/cmm versus 0% in those with nadir platelet counts of > 30 x 10(3)/cmm (P=.06); all patients with fungal infections had nadir platelet counts of < or =30 x 10(3)/cmm before fungal infection . Nadir in platelet count preceded the first major infection by a median of 7 days . Pretransplant TPO level did not differ between survivors (mean 103 pg/ml) or nonsurvivors (mean 144 pg/ml) . After the transplantation, TPO levels increased in both groups . TPO level peaked at Day 7 and subsequently declined in survivors . Nonsurvivors had persistent thrombocytopenia despite a progressive rise in TPO level; TPO level was significantly higher at Day 7 (P=.02), Day 9 (P=.0019), and Day 14 (P=.04) in nonsurvivors compared with survivors . CONCLUSION: Persistent thrombocytopenia portended a poor outcome in liver transplant recipients and was not related to low TPO levels . Thrombocytopenia preceded infections and identified a subgroup of liver transplant patients susceptible to early major infections; its precise role in fungal infections warrants validation in larger studies.

Zentralbl Bakteriol, 1999 Dec, 289(5-7), 655 - 65
Chemoprophylaxis for Lyme borreliosis?
Stanek G, Kahl O.
Chemoprophylaxis is a term which describes treatment with an antimicrobial chemotherapeutic before, during or shortly after an actual or suspected exposure to an infectious agent in order to prevent clinical disease, which may be severe or even fatal . Lyme borreliosis is considered the most frequent ixodid-tick-transmitted human bacterial infection in the northern hemisphere . For several years there has been a debate on the prophylactic application of antimicrobial chemotherapeutics after an attached Ixodes tick was removed . Would this measure prevent a subsequent borrelia infection and would it be practical? People are exposed to tick-bites mostly during leisure spent in recreational areas which are often tick infested . The proportion of I . ricinus ticks infected with B . burgdorferi s . l . varies from area to area and in a given area also from year to year (infection rate up to a maximum of 55%) . The transmission rate strongly depends on the duration of feeding, but it could be shown that the critical time of feeding is much shorter for European I . ricinus than for the North American I . scapularis or I . pacificus ticks . Nevertheless, even the low risk of complications despite the very good chance of treating erythema migrans successfully seems to justify prophylactic treatment for some investigators whilst others do not see an argument for this . Double blinded studies in the USA showed a relatively low frequency of illness after vector tick-bite and absence of disseminated disease manifestations . The efficacy of prophylactic antibiotic treatment after tick-bites is not established . Suggestions to examine removed ticks for borrelia in order to obtain indication for prophylactic antibiotic treatment will fail in practice because of high costs and uncertainty in verifying the transmission . Do we need blinded studies in central Europe on a representative number of cases, although it is known that Lyme borreliosis can be treated effectively even in its second and third stage and has never caused a fatal outcome? We conclude that only a reliable diagnosis of symptoms is the basis for a rational antibiotic treatment, and that instead of chemoprophylaxis for Lyme borreliosis after a vector tick-bite the wait and watch policy is recommended.

Anticancer Res, 1999 Jul-Aug, 19(4B), 2969 - 71
Presence of defensin in epithelial Langerhans cells adjacent to oral carcinomas and precancerous lesions; Mizukawa N et al.; We aimed to immunohistochemically study the localization of defensin (HNPs), a family of peptides with antimicrobial and cytotoxic activity, in oral tumor tissue . Therefore, tissue sections were embedded in paraffin, and defensin was immunostained by the streptavidin-biotin coupled peroxidase method . Langerhans cells were confirmed by indirect immunostaining with anti-S-100 protein polyclonal antibody . Melanocytes were stained with Fontana-Masson's stain . Neutrophils and intimal cells were stained by anti-defensin antibody . Langerhans cells in normal epithelium or dysplasic epithelium adjacent to squamous cell carcinoma and precancerous lesion were also stained . Defensins (HNPs) are nonspecific peptides that occur in neutrophils and protect against bacteria, fungi, and tumor cells . Since defensins are also found in epithelial Langerhans cells adjacent to tumor tissue, these peptides most likely have a role in tumor immunity.

Int J Dermatol, 2000 Jan, 39(1), 59 - 69
Climatotherapy of atopic dermatitis at the Dead Sea: demographic evaluation and cost-effectiveness; Harari M et al.; BACKGROUND: About 21% of the patients coming yearly to the DMZ Clinic at the Dead Sea for climatotherapy suffer from atopic dermatitis . This is a common, chronic, and relapsing disease which necessitates drug treatment (topical corticosteroids, antimicrobials, antihistamines, or immunomodulators), phototherapy, or climatotherapy . Objective and methods As the improvement in the condition of patients after 4 weeks of climatotherapy at the Dead Sea is remarkable, we undertook to evaluate the demographic factors that have the strongest impact on this beneficial effect, in adults and children . The major factors studied were: gender, previous medical history, previous stays at the Dead Sea, skin type, skin involvement, age, and duration of treatment . Results A retrospective study of 1718 patients revealed that previous treatments at the Dead Sea and stays longer than 4 weeks caused a clearance greater than 95%, the length of sun exposure was no longer than 5 h daily, and there was no impact of the percentage of skin involvement on the clearance of patients staying more than 4 weeks . CONCLUSION: s Climatotherapy of atopic dermatitis at the Dead Sea is a highly effective modality for treating this disease . It is also a highly cost-effective method, as the patients take no medications and experience no side-effects . Successful climatotherapy of atopic dermatitis requires strict medical supervision throughout the whole length of the patient's stay on shore.

Int J Dermatol, 2000 Jan, 39(1), 45 - 50
Azithromycin for the treatment of acne; Fernandez-Obregon AC; BACKGROUND: Acne affects a large number of young adults, including women, who often present with facial as well as truncal involvement . Systemic antimicrobial agents currently used for the reduction of inflammatory papules and cysts require frequent administration and are sometimes associated with uncomfortable side-effects contributing to a decrease in compliance . METHODS: Ninety-nine episodes of inflammatory acne in 79 patients treated with oral antimicrobial agents were studied retrospectively over a period of 46 weeks . Patients were treated with tetracycline, erythromycin, minocycline, and doxycycline, the most commonly prescribed oral antimicrobials used to treat acne . Individuals that were unable to tolerate this therapy or had failed conventional therapy were treated with the azalide antibiotic azithromycin, given in a single oral 250-mg dose three times a week . The other agents were administered daily in divided doses as is current practice . Patients were also on topical care . RESULTS: The efficacy and reported side-effects were examined for all agents . Significant improvement was noted in 4 weeks . All agents were effective in reducing inflammatory lesions and improving acne . Azithromycin produced a slightly higher percentage of patients with a greater than 80% reduction in their inflammatory acne lesions (85.7%) vs . an average of 77.1% for all other agents . All differences observed were not statistically significant . CONCLUSIONS: The results show that azithromycin is a safe and effective alternative in the treatment of inflammatory acne with few side-effects and good compliance, and suggest the need for further investigation with a clinical trial that will compare the long-term efficacy and tolerability.

Aliment Pharmacol Ther, 2000 Feb, 14(2), 211 - 5
Furazolidone combination therapies for Helicobacter pylori infection in the United States; Graham DY et al.; BACKGROUND: Antibiotic resistance has begun to impair the ability to cure Helicobacter pylori infection . AIM: To evaluate furazolidone as a component of combination therapies for treatment of H . pylori infection in the United States . METHODS: Patients with active H . pylori infection received furazolidone combination therapy for 14 days (furazolidone 100 mg and tetracycline 500 mg t.d.s.; omeprazole 20 mg o.d . in the morning and, depending on the pre-treatment antimicrobial susceptibility pattern, 500 mg of metronidazole or clarithromycin t.d.s.) . RESULTS: A total of 27 patients received the metronidazole containing combination (cure rate 100%) and seven received the clarithromycin combination (cure rate 86%) . Overall the cure rates for intention-to-treat was 97% (95% CI: 85% to 100%) . The single failure took the clarithromycin containing combination for only 2 days (per protocol cure rate = 100%) . Side-effects were common and led to discontinuation of therapy in 26% of patients . An attempt to eliminate metronidazole and clarithromycin and use furazolidone, tetracycline, and lansoprazole b.d . produced an unsatisfactory cure rate of 72% . CONCLUSION: Furazolidone combination therapy appears to be effective . Additional studies with different antimicrobial combinations and duration of therapy are warranted.

Semin Pediatr Neurol, 1999 Dec, 6(4), 288 - 98
Advances in antimicrobial therapy; Pavia AT; Despite several decades of improved therapy and prevention of infectious diseases, infectious pathogens remain major causes of morbidity and mortality in humans worldwide . Among the most complex and daunting problems facing medical science is the evolution of antibiotic resistance among many common and once easily-treated infectious agents . This review summarizes the status of newer antimicrobial agents that have utility against pathogens infecting the central nervous system.

Semin Pediatr Neurol, 1999 Dec, 6(4), 267 - 77
Neurocysticercosis and acquired cerebral toxoplasmosis in children; Mitchell WG; Neurocysticercosis, prevalent wherever pigs are raised in the presence of poor sanitation, is the most common identifiable cause of new-onset epilepsy throughout the developing world . As immigration patterns have changed, children with neurocysticercosis are seen throughout the United States . Acute cysticercosis, the most common manifestation in children, reflects the host response to the dying parasite . Children typically present with seizures and have an excellent prognosis . Neuroimaging demonstrates a single ring or nodular enhancing lesion surrounded by edema . Short-term anticonvulsant therapy is indicated, but treatment with antiparasitic agents is not required . Other forms, such as active cysts (intact organism), intraventricular or subarachnoid racemous cysticercosis, and cysticercal meningoencephalitis, are less common manifestations of parasitic infection . Toxoplasmosis, caused by the parasite Toxoplasma gondii, can be acquired by ingestion of infected undercooked meat or from oocytes shed in cat feces . Acquired cerebral toxoplasmosis, due to primary or reactivated infections, rarely occurs in immunocompetent children . In children who are immunodeficient as the result of AIDS, chemotherapy, tissue transplantation, or congenital immunodeficiency, toxoplasmosis may be difficult to distinguish from cerebral lymphoma . A variety of techniques, including neuroimaging, Thallium-201 SPECT, polymerase chain reaction analysis of CSF, and special histological methods, may be used to diagnose acquired toxoplasmosis . Antiparasitic therapy, using pyrimethamine and sulfadiazine, and serial neuroimaging often enable clinicians to differentiate toxoplasmosis from other central nervous system lesions . Toxoplasmosis may respond to other antimicrobials, including macrolide antibiotics, dapsone, clinidamycin, and atovaquone . Suppressive treatment is generally required for life in immunodeficient patients . Immunodeficient children with acquired toxoplasmosis have high rates of mortality and neurological sequelae.

Adv Perit Dial, 1998, 14, 131 - 6
Management of peritonitis in automated peritoneal dialysis patients; Diaz-Buxo JA; The management of peritonitis in patients undergoing automated peritoneal dialysis (APD) deserves special consideration due to the technical differences between APD modalities and continuous ambulatory peritoneal dialysis (CAPD) . The use of very short exchanges may preclude the prompt diagnosis of peritonitis by diluting the peritoneal-cell population and causing spuriously low cell counts and clear effluent . Very long diurnal cycles can have the opposite result and give a falsely elevated cell count . The effluent from the multiple automated exchanges must be visually examined before being discarded in order to make a prompt diagnosis . Direct drainage of effluent into the sewage without inspection should be avoided . If direct drainage becomes a common practice, other alternatives such as on-line cell counters or chemical detectors of possible infection will be necessary . The recommendations for antimicrobial therapy developed for CAPD apply as well to APD . If single-day dosage is to be used, the longer exchanges of APD are ideal for intra-peritoneal delivery of antibiotics.

Respir Physiol, 1999 Dec 1, 118(2-3), 77 - 83
Physiology and pathology of tracheobronchial glands; Finkbeiner WE; The tracheobronchial glands, composed of mucous and serous secretory cells, provide a mucin-rich, antimicrobial-rich secretion for the conducting airways . The secretory processes of these cells are under complex neurohumoral control . Several diseases demonstrate considerable increases in the volume of secretory glands, the amount of glandular secretions or the character of the secretory product . The role of the tracheobronchial glands in the pathophysiology of chronic bronchitis, asthma and cystic fibrosis is discussed.

J Leukoc Biol, 2000 Jan, 67(1), 34 - 9
Human monocytic U937 cells transfected with human hepatic inducible nitric oxide synthase exhibit leishmanicidal activity; Bertholet S et al.; In mice, the high inducible synthesis of nitric oxide (NO) resulting from inducible NO synthase (iNOS, NOS2) expression by macrophages (Mphi) is considered an essential component of the protective immune response against infection by intracellular pathogens . Conversely, in humans, the question of a role for NO as an antimicrobial defense mechanism has been the subject of much debate . Recently, however, iNOS expression by human Mphi and formation of NO or its derivatives have been reported both in vivo and in vitro, strongly suggesting that human Mphi are indeed capable of inducible NO synthesis . However, the conditions allowing NO production by human Mphi in culture remain poorly defined, rendering more difficult the study of the effector functions of NO in these cells . To alleviate this problem, cells of the U937 monocytoid line were engineered to express iNOS by transfection with human hepatic iNOS (DFGiNOS), leading to production of NO on supplementation with the cofactor tetrahydrobiopterin . We report that U937 cells, when differentiated with 1,25-dihydroxyvitamin D3 and retinoic acid, acquire a phenotype allowing infection by Leishmania parasites and maintain viable intracellular microorganisms up to 72 h post-infection . Leishmania survival in DFGiNOS cells is strongly decreased when the cells are treated with tetrahydrobiopterin . Intracellular killing is evident by 24 h and increases up to 72 h post-infection, and is inhibited by L-N5-(1-iminoethyl)ornithine, an inhibitor of NO synthesis . In contrast, superoxide anion does not appear to play a role in the killing of Leishmania by DGFiNOS U937 cells . The relevance of this model to the study of the mechanisms of intracellular killing by human macrophages is discussed.

Drug Saf, 2000 Jan, 22(1), 53 - 72
Drug-induced diarrhoea; Chassany O et al.; Diarrhoea is a relatively frequent adverse event, accounting for about 7% of all drug adverse effects . More than 700 drugs have been implicated in causing diarrhoea; those most frequently involved are antimicrobials, laxatives, magnesium-containing antacids, lactose- or sorbitol-containing products, nonsteroidal anti-inflammatory drugs, prostaglandins, colchicine, antineoplastics, antiarrhythmic drugs and cholinergic agents . Certain new drugs are likely to induce diarrhoea because of their pharmacodynamic properties; examples include anthraquinone-related agents, alpha-glucosidase inhibitors, lipase inhibitors and cholinesterase inhibitors . Antimicrobials are responsible for 25% of drug-induced diarrhoea . The disease spectrum of antimicrobial-associated diarrhoea ranges from benign diarrhoea to pseudomembranous colitis . Several pathophysiological mechanisms are involved in drug-induced diarrhoea: osmotic diarrhoea, secretory diarrhoea, shortened transit time, exudative diarrhoea and protein-losing enteropathy, and malabsorption or maldigestion of fat and carbohydrates . Often 2 or more mechanisms are present simultaneously . In clinical practice, 2 major types of diarrhoea are seen: acute diarrhoea, which usually appears during the first few days of treatment, and chronic diarrhoea, lasting more than 3 or 4 weeks and which can appear a long time after the start of drug therapy . Both can be severe and poorly tolerated . In a patient presenting with diarrhoea, the medical history is very important, especially the drug history, as it can suggest a diagnosis of drug-induced diarrhoea and thereby avoid multiple diagnostic tests . The clinical examination should cover severity criteria such as fever, rectal emission of blood and mucus, dehydration and bodyweight loss . Establishing a relationship between drug consumption and diarrhoea or colitis can be difficult when the time elapsed between the start of the drug and the onset of symptoms is long, sometimes up to several months or years.

J Urol, 2000 Feb, 163(2), 561 - 6; discussion 566-7
Cost analysis of the treatment of vesicoureteral reflux: a computer model; Mathews R et al.; PURPOSE: Surgical intervention for vesicoureteral reflux is generally limited to children who have recurrent infection despite adequate antimicrobial prophylaxis or in whom compliance with followup cannot be ensured . In addition, surgical therapy is considered in children with persistent reflux after a reasonable period of surveillance . We used a model based on the management of a theoretical population of girls with various grades of reflux and followed the costs incurred during a 5-year management period . MATERIALS AND METHODS: The literature on vesicoureteral reflux was used to create a set of assumptions regarding epidemiology, likelihood of resolution, need for operative intervention, risk of infection and appropriate regimen for nonoperative surveillance . These parameters were evaluated in infants and children as noted in the literature . A 5-year management period was considered . Patients in whom reflux did not resolve with medical management at the end of 5 years were assumed to have undergone surgical correction . Costs were calculated based on the amounts billed, managed care reimbursement and Medicaid reimbursement in Maryland . The costs of up front surgical management were calculated and compared to those of 5 years of standard management . All costs were discounted at a rate of 10% . RESULTS: Calculated costs of standard management were lower for lower grades than those for higher grades of reflux . The costs of surgical management were lower than those of standard management for higher reflux grades using nondiscounted costs . However, when costs were discounted to present value, the costs of standard management were significantly lower than those of up-front surgery for all scenarios studied . CONCLUSIONS: The cost of vesicoureteral reflux is considerable when whole patient groups are considered . Using cost as the only parameter the standard management of reflux is less costly than up-front surgery . In the individual surgical intervention usually is predicated by patient and family factors which were not considered in this model . This computer based construct allows data from different institutions to be analyzed to project costs of the management of reflux.

Microb Drug Resist, 1999 Winter, 5(4), 289 - 93
Antimicrobial susceptibility of equine isolates of Actinobacillus spp . and identification of beta-lactamases in some strains; Sternberg S et al.; A total number of 149 Actinobacillus strains isolated from clinical samples (73 strains) and from the oral cavity of healthy horses (76 strains) were tested for their susceptibility to 17 antimicrobial substances . The antibiograms were generally very similar between the various strains and no differences could be clearly correlated to either phenotype or source of isolates . However, when tested against penicillin, ampicillin, trimethoprim-sulfa, and streptomycin, small groups of strains with what appeared to be acquired resistance could be identified . Eight of the penicillin-resistant strains were found to produce beta-lactamase . The beta-lactamases appeared to be bound tightly to the cell wall, thereby frustrating further characterization by isoelectric focusing . Plasmids of approximately 3 kb were found in four out of seven beta-lactamase-producing strains submitted to plasmid analysis.

Microb Drug Resist, 1999 Winter, 5(4), 265 - 70
Activity of 16 antimicrobial agents against drug-resistant strains of Mycobacterium tuberculosis; Fattorini L et al.; The in vitro activity of 16 antimicrobial agents against 46 drug-resistant strains of Mycobacterium tuberculosis recently isolated from Italian patients was determined . As for first-line antituberculosis drugs, while isoniazid was ineffective against all the strains tested, resistance to streptomycin, rifampicin, pyrazinamide, and ethambutol was 80.4%, 71.7%, 39.1%, and 8.7%, respectively . Among second-line antituberculous drugs, resistance to ciprofloxacin, ofloxacin, and sparfloxacin and to amikacin and kanamycin was around 20% . About 10% of the strains were resistant to capreomycin and cycloserine and 4.3% were resistant to ethionamide; no strain was found to be resistant to thiacetazone, para-aminosalicylic acid, and viomycin . Although all strains displayed a rather continuous distribution of minimal inhibitory concentrations (MICs), a bimodal distribution was observed for rifampicin, amikacin, and kanamicin, with very high MIC values for resistant strains; relatively low MICs were found for fluoroquinolone-resistant strains . Among the small number of strains resistant to second-line agents, low resistant levels were observed . Restriction fragment length polymorphism analysis showed few strain clusters with resistance to first-line antituberculous drugs and aminoglycosides, fluoroquinolones, or both . Altogether, these results showed that second-line agents were still active against the isoniazid-resistant and multiply first-line resistant strains tested, with none or low resistance levels; these observations can be of importance for the treatment of multidrug-resistant tuberculosis in Italy.

Food Addit Contam, 1999 Aug, 16(8), 339 - 51
Microbiological and chemical identification of antimicrobial drugs in kidney and muscle samples of bovine cattle and pigs; Myllyniemi AL et al.; Microbiological and chemical identification of antimicrobial drug residues was attempted in 95 kidney and 76 muscle samples from 58 cattle, 36 pigs and one horse which had revealed kidneys positive to an inhibitor test . Information on pre-slaughter medication with one antimicrobial drug was available for 63% of the carcasses . Microbiological identification was performed by agar diffusion using 17 or 18 combinations of eight test bacteria, varying medium pH and three substances blocking the action of certain antimicrobials . Sample activity patterns compiled from inhibition zone diameters on test plates were compared with those obtained with standard antimicrobial solutions both visually and by locating the minimal sum of absolute pairwise differences over the tests . Chemical identification of residues was based on liquid chromatography . In kidney samples containing one microbiologically-identified antimicrobial the two methods gave fully consistent results with tetracyclines (15/15) and fluoroquinolenes (8/8) . Preparation and storage of the kidney samples before chemical analyses appeared to influence the chemical identification of penicillin G . The results were consistent in 37 of the 41 samples stored without homogenization at -70 degrees C . The residue was identified by chemical means only in six and neither microbiologically nor chemically in four kidney samples with information on pre-slaughter medication . The same residue as in the kidney samples was identifiable microbiologically in 41% of the muscle samples of the same carcasses . The results show that the microbiological method is well suited for identification of antibiotic residues . They indicate further that an enhanced resolution with a reduced combination of plates is attainable.

Circulation, 2000 Jan 25, 101(3), 252 - 7
Infections, inflammation, and the risk of coronary heart disease; Roivainen M et al.; BACKGROUND: The role of infections and inflammation in the pathophysiology of coronary heart disease is emerging . We studied the independent and joint effects of these 2 components on coronary risk . METHODS AND RESULTS: We measured baseline levels of C-reactive protein (CRP) and antibodies to adenovirus, enterovirus, cytomegalovirus, and herpes simplex virus as well as to Chlamydia pneumoniae (Cpn) and Helicobacter pylori in 241 subjects who suffered either myocardial infarction or coronary death during the 8.5-year trial in the Helsinki Heart Study, a coronary primary prevention trial . The 241 controls in this nested case-control study were subjects who completed the study without coronary events . Antibody levels to herpes simplex type I (HSV-1) and to Cpn were higher in cases than in controls, whereas the distributions of antibodies to other infectious agents were similar . Mean CRP was higher in cases (4.4 versus 2.0 mg/L; P<0.001), and high CRP increased the risks associated with smoking and with high antimicrobial antibody levels . The odds ratios in subjects with high antibody and high CRP levels were 25.4 (95% CI 2.9-220.3) for HSV-1 and 5.4 (95% CI 2.4-12.4) for Cpn compared with subjects with low antibody levels and low CRP . High antibody levels to either HSV-1 or to Cpn increased the risk independently of the other, and their joint effect was close to additive . CONCLUSIONS: Two chronic infections, HSV-1 and Cpn, increase the risk of coronary heart disease . The effect is emphasized in subjects with ongoing inflammation, denoted by increased CRP levels.

Am J Physiol Lung Cell Mol Physiol, 2000 Jan, 278(1), L90 - 8
Enhanced anti-influenza activity of a surfactant protein D and serum conglutinin fusion protein; Hartshorn KL et al.; We previously demonstrated that bovine serum conglutinin has markedly greater ability to inhibit influenza A virus (IAV) infectivity than other collectins . We now show that recombinant conglutinin and a chimeric protein containing the NH(2) terminus and collagen domain of rat pulmonary surfactant protein D (rSP-D) fused to the neck region and carbohydrate recognition domain (CRD) of conglutinin (termed SP-D/Cong(neck+CRD)) have markedly greater ability to inhibit infectivity of IAV than wild-type recombinant rSP-D, confirming that the potent IAV-neutralizing activity of conglutinin resides in its neck region and CRD . Furthermore, by virtue of incorporation of the NH(2) terminus and collagen domain of SP-D, SP-D/Cong(neck+CRD) caused substantially greater aggregation of IAV particles and enhancement of neutrophil binding of, and H(2)O(2) responses to, IAV than recombinant conglutinin or recombinant rSP-D . Hence, SP-D/Cong(neck+CRD) combined favorable antiviral and opsonic properties of conglutinin and SP-D . This study demonstrates an association of specific structural domains of SP-D and conglutinin with specific functional properties and illustrates that antimicrobial activities of wild-type collectins can be enhanced through recombinant strategies.

Am J Physiol Lung Cell Mol Physiol, 2000 Jan, 278(1), L51 - 8
Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins; van Wetering S et al.; Secretory leukocyte proteinase inhibitor (SLPI) is a serine proteinase inhibitor that is produced locally in the lung by cells of the submucosal bronchial glands and by nonciliated epithelial cells . Its main function appears to be the inhibition of neutrophil elastase (NE) . Recently, NE was found to enhance SLPI mRNA levels while decreasing SLPI protein release in airway epithelial cells . Furthermore, glucocorticoids were shown to increase both constitutive and NE-induced SLPI mRNA levels . In addition to NE, stimulated neutrophils also release alpha-defensins . Defensins are small, antimicrobial polypeptides that are found in high concentrations in purulent secretions of patients with chronic airway inflammation . Like NE, defensins induce interleukin-8 production in airway epithelial cells . This induction is sensitive to inhibition by the glucocorticoid dexamethasone and is prevented in the presence of alpha(1)-proteinase inhibitor . The aim of the present study was to investigate the effect of defensins on the production of SLPI and the related NE inhibitor elafin/SKALP in primary bronchial epithelial cells (PBECs) . Defensins significantly increase SLPI protein release by PBECs in a time- and dose-dependent fashion without affecting SLPI mRNA synthesis . In the presence of alpha(1)-proteinase inhibitor, the defensin-induced SLPI protein release is further enhanced, but no effect was observed on SLPI mRNA levels . Dexamethasone did not affect SLPI protein release from control or defensin-treated PBECs . In addition, we observed a constitutive release of elafin/SKALP by PBECs, but this was not affected by defensins . The present results suggest a role for defensins in the dynamic regulation of the antiproteinase screen in the lung at sites of inflammation.

Tuber Lung Dis, 1998, 79(2), 111 - 8
Genotypic characterization of drug-resistant Mycobacterium tuberculosis isolates from Peru; Escalante P et al.; SETTING: Twenty-nine epidemiological unrelated and mostly multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains from Peruvian patients . OBJECTIVE: To investigate the molecular genetics of MDR-TB strains recovered in a Latin American country . DESIGN: Antimicrobial agent susceptibility testing, major genetic group designation, IS6110 fingerprinting, spoligotyping, and automated deoxyribonucleic acid sequencing of regions of the katG, rpoB, embB, gyrA, and pncA genes with mutations commonly associated with drug resistance . RESULTS: Nineteen isolates were found to be multidrug-resistant by susceptibility testing . IS6110 typing showed that virtually all isolates were unique and therefore had independently acquired drug resistance . Seventy-nine percent of isoniazid-resistant strains had a Ser315Thr amino acid change in KatG . Ninety-five percent of rifampin-resistant isolates had amino acid replacements in the rifampin-resistance determining region of RpoB . Six of 11 ethambutol-resistant strains had EmbB alterations . Eleven pyrazinamide-resistant strains had distinct mutations in pncA . CONCLUSION: Virtually all organisms evolved drug resistance independently . The types of drug resistance-associated mutations identified were very similar to changes occurring in isolates from other areas of the world . Nucleotide sequence-based strategies for rapid detection of drug resistance-conferring mutants will be applicable to organisms recovered in Peru, and potentially other areas of Latin America.

Tuber Lung Dis, 1998, 79(1), 3 - 29
Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update; Ramaswamy S et al.; Knowledge of the molecular genetic basis of resistance to antituberculous agents has advanced rapidly since we reviewed this topic 3 years ago . Virtually all isolates resistant to rifampin and related rifamycins have a mutation that alters the sequence of a 27-amino-acid region of the beta subunit of ribonucleic acid (RNA) polymerase . Resistance to isoniazid (INH) is more complex . Many resistant organisms have mutations in the katG gene encoding catalase-peroxidase that result in altered enzyme structure . These structural changes apparently result in decreased conversion of INH to a biologically active form . Some INH-resistant organisms also have mutations in the inhA locus or a recently characterized gene (kasA) encoding a beta-ketoacyl-acyl carrier protein synthase . Streptomycin resistance is due mainly to mutations in the 16S rRNA gene or the rpsL gene encoding ribosomal protein S12 . Resistance to pyrazinamide in the great majority of organisms is caused by mutations in the gene (pncA) encoding pyrazinamidase that result in diminished enzyme activity . Ethambutol resistance in approximately 60% of organisms is due to amino acid replacements at position 306 of an arabinosyltransferase encoded by the embB gene . Amino acid changes in the A subunit of deoxyribonucleic acid gyrase cause fluoroquinolone resistance in most organisms . Kanamycin resistance is due to nucleotide substitutions in the rrs gene encoding 16S rRNA . Multidrug resistant strains arise by sequential accumulation of resistance mutations for individual drugs . Limited evidence exists indicating that some drug resistant strains with mutations that severely alter catalase-peroxidase activity are less virulent in animal models . A diverse array of strategies is available to assist in rapid detection of drug resistance-associated gene mutations . Although remarkable advances have been made, much remains to be learned about the molecular genetic basis of drug resistance in Mycobacterium tuberculosis . It is reasonable to believe that development of new therapeutics based on knowledge obtained from the study of the molecular mechanisms of resistance will occur.

Biochem Pharmacol, 2000 Feb 15, 59(4), 317 - 20
Granulysin: a novel antimicrobial peptide of cytolytic T lymphocytes and natural killer cells; Krensky AM; Granulysin is a novel antimicrobial protein produced by human cytolytic T lymphocytes and natural killer cells . It is active against a broad range of microbes, including Gram-positive and Gram-negative bacteria, fungi, and parasites . The fact that it kills Mycobacterium tuberculosis is particularly important, since the current vaccine (Bacille Calmette-Guerin, BCG) is of limited efficacy and antibiotic resistance is increasing . Although functionally related to other antibacterial peptides, defensins and magainins, granulysin is structurally distinct . Like porcine NK lysin and amoebapores made by Entamoeba histolytica, granulysin is related to saposins, small lipid-associated proteins present in the central nervous system . The identification of this novel molecule indicates a broader and perhaps more significant role for T lymphocytes in both innate and acquired antimicrobial defenses.

J Control Release, 2000 Jan 3, 63(1-2), 175 - 89
Polyurethane coatings release bioactive antibodies to reduce bacterial adhesion; Rojas IA et al.; This study describes the formulation of a biomedical grade polyurethane hydrogel coating containing solid dispersed bioactive antibodies cast from an organic solvent onto a model polymer biomaterial substrate . A prepolymer dispersion in anhydrous isopropanol containing a uniformly distributed slurry of 22 microm sieved commercial lyophilized polyclonal pooled human immunoglobulin G (IgG) solids was coated onto polymer substrates by simple immersion . Maximum antibody release was approximately 50 microg/cm(2) from a 15% w/w IgG polymer coating . In vitro antimicrobial studies utilized Escherichia coli to compare performance of bare uncoated tubing, hydrogel-coated tubing with added aqueous phase antibodies, and antibody-dispersed hydrogel-coated tubing . Bacterial adhesion was reduced significantly (p<0.05) in the presence of antibodies with the greatest reduction seen with the antibody releasing coating . The presence of antibody also significantly enhanced the killing of the bacteria in an in vitro opsonophagocytic assay using freshly isolated blood neutrophils over 2 h indicating that antibody bioactivity is maintained . This controlled release polyurethane hydrogel coating imparts infection resistance by exploiting the low adhesive properties of the biomedical grade hydrogel and the intrinsic bioactive role of the antibodies to reduce bacterial adhesion and promote clearance via natural immune mechanisms.

J Anim Sci, 1999 Dec, 77(12), 3208 - 14
Effect of feed intake on antimicrobially induced increases in porcine serum insulin-like growth factor I; Hathaway MR et al.; This study was conducted to determine whether an antimicrobially induced (ASP-250) increase in serum IGF-I was the result of differences in feed intake . Serum IGF-I concentrations were measured in crossbred pigs that were fed a control diet or a diet supplemented with ASP-250 either for ad libitum consumption or limited to 85% of the control pigs' consumption . The pigs that consumed either diet ad libitum, control or ASP-250, consumed similar quantities of feed . The ASP-250 ad libitum-intake pigs had serum IGF-I concentrations that were greater (P<.01) than those of their ad libitum-intake control littermates . Similarly, the ASP-250 limit-fed pigs had serum IGF-I concentrations that were greater (P<.01) than those of the controls . Although the serum IGF-I concentrations of pigs fed the ASP-250-supplemented diet for ad libitum intake were greater than the serum IGF-I concentrations of the pigs limit-fed the ASP-250-supplemented diet, the differences were not significant (P<.08) . The ASP-250-fed pigs had higher serum IGF binding protein (BP)-3 concentrations than did their control littermates (P<.003) . A time course of antimicrobially induced alterations in serum IGF-I concentrations revealed that the effect of increased serum IGF-I levels in ASP-250-supplemented pigs (P<.02) was observed within 4 d and was maintained throughout the 4-wk study . These findings show that feed intake is not responsible for the increase in serum IGF-I observed with ASP-250 supplementation . Additionally, the antimicrobially induced increase in serum IGF-I concentrations occurs within a few days after initiation of the treatment.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 458 - 61
In vitro activities of rabeprazole, a novel proton pump inhibitor, and its thioether derivative alone and in combination with other antimicrobials against recent clinical isolates of Helicobacter pylori; Kawakami Y et al.; The MICs of rabeprazole sodium (RPZ), a newly developed benzimidazole proton pump inhibitor (PPI), against 133 clinical Helicobacter pylori strains revealed a higher degree of activity than the another two PPIs, lansoprazole and omeprazole . Time-kill curve assays of RPZ, when combined with amoxicillin, clarithromycin, or metronidazole, disclosed that synergistic effects were demonstrated in combination with each antibiotic examined . Moreover, no apparent antagonistic effect appeared among all of the strains tested.

Antimicrob Agents Chemother, 2000 Feb, 44(2), 283 - 6
Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex; Tomioka H et al.; WQ-3034 is a newly synthesized acidic fluoroquinolone . We assessed its in vitro activity against Mycobacterium tuberculosis and M . avium complex using levofloxacin (LVFX), ciprofloxacin (CPFX), sparfloxacin (SPFX), and KRM-1648 (KRM) as reference drugs . The MICs of these agents were determined by the agar dilution method with 7H11 medium . The MICs at which 50 and 90% of the test strains were inhibited (MIC(50)s, and MIC(90)s, respectively) for the test quinolones for rifampin (RMP)-susceptible M . tuberculosis strains were in the order SPFX < LVFX </= WQ-3034 </= CPFX, while those for RMP-resistant M . tuberculosis strains were in the order SPFX </= WQ-3034 </= LVFX < CPFX . The MICs of KRM for RMP-susceptible M . tuberculosis were much lower than those of the test quinolones, while the MIC(90) of KRM for RMP-resistant M . tuberculosis strains was higher than those of the quinolones . The MIC(50)s and MIC(90)s of the test drugs for M . avium were in the order KRM < SPFX < CPFX </= WQ-3034 </= LVFX, while those for M . intracellulare were in the order KRM < SPFX < WQ-3034 LVFX </= CPFX . Next, we compared the antimicrobial activities of the test drugs against M . tuberculosis organisms residing in cells of the Mono Mac 6 macrophage (Mphi)-like cell line (MM6-Mphis) and of the A-549 type II alveolar cell line (A-549 cells) . When drugs were added at the concentration that achieves the maximum concentration in blood, progressive killing or inhibition of the M . tuberculosis organisms residing in MM6-Mphis and A-549 cells was observed in the order KRM > SPFX >/= LVFX > WQ-3034 > CPFX . The efficacies of all quinolones against intracellular M . tuberculosis organisms were significantly lower in A-549 cells than in MM6-Mphis . WQ-3034 at the MIC caused more marked growth inhibition of intramacrophage M . tuberculosis than did LVFX . These findings indicate that the in vitro anti-M . tuberculosis activity of WQ-3034 is greater than that of CPFX and is comparable to that of LVFX.

J Cell Sci, 2000 Feb, 113 ( Pt 3), 461 - 9
Penaeidins, antimicrobial peptides with chitin-binding activity, are produced and stored in shrimp granulocytes and released after microbial challenge; Destoumieux D et al.; Penaeidins are members of a new family of antimicrobial peptides isolated from a crustacean, which present both Gram-positive antibacterial and antifungal activities . We have studied the localization of synthesis and storage of penaeidins in the shrimp Penaeus vannamei . The distribution of penaeidin transcripts and peptides in various tissues reveals that penaeidins are constitutively synthesized and stored in the shrimp haemocytes . It was shown by immunocytochemistry, at both optical and ultrastructural levels, that the peptides are localized in granulocyte cytoplasmic granules . The expression and localization of penaeidins were further analysed in shrimp subjected to microbial challenge . We found that (1) penaeidin mRNA levels decrease in circulating haemocytes in the first 3 hours following stimulation and (2) an increase in plasma penaeidin concentration occurs after microbial challenge, together with (3) a penaeidin immunoreactivity in cuticular tissue, which can be related to the chitin-binding activity we demonstrate here for penaeidins.

Ther Umsch, 1999 Dec, 56(12), 691 - 7
{Antibiotics, new pathogens, new drug resistance}; Kern WV; The 20th century is the century of the discovery of numerous pathogenic microorganisms . It is also the century of discovery of antimicrobial drugs and the beginning of the antibiotic era . While the development of antifungal drugs and of antivirals is on its rise, many infectious disease physicians and microbiologists feel that we might be on the edge of the beginning of the post-antibiotic era--50 years after antibiotic use in man and animals . Antibiotics have certainly been a major progress in modern medicine . Mortality and morbidity from many infectious diseases have been substantially reduced by effective antimicrobial therapy . The use of antibiotics has also been a prerequisite for major advances in clinical oncology, transplantation medicine, and surgery . The emergence and spread of resistant pathogens, however, has necessitated the development of broader and more active drugs and has resulted in excessive antimicrobial drug use with consequent selective pressure . Every 3rd patient admitted to a hospital is given antibiotics--often in the form of stepwise escalated therapy eventually including combinations of expensive agents . If the aim is to minimize the emergence of resistance and to contain costs, a much more critical indication for antimicrobial drug therapy will be necessary . Also, programmes on a local, regional, and perhaps even national level will be needed to help rationalize antimicrobial drug use.

Sangyo Eiseigaku Zasshi, 1999 Nov, 41(6), 183 - 9
{Influence on diagnosis of Helicobacter pylori infection in 13C urea breath test of existence of dead space gas}; Kikuchi H et al.; The 13C-urea breath test is a noninvasive analysis for the detection of Helicobacter pylori infection and is valuable for judging the effects of antimicrobial treatment . Up to date the most popular technique for 13C-urea breath test: UBT, is performed by collecting expired gas into an aluminum bag, but the result is considered to be influenced in the diagnosis of Helicobacter pylori infection by the existence of anatomical dead space gas . We therefore introduced a new technique to measure 13CO2 and 12CO2 continuously during expiration, identified the correct alveolar gas, and excluded the effect of anatomical dead space . Subjects were 127 males and 8 females . We compared the diagnostic accuracy of these aluminum bag and continuous measurement methods . We adopted serological IgG positive and barium-meal study positive cases as a gold standard for the diagnosis . Diagnostic accuracy by continuous measurement was superior to that by the aluminum bag method . We should pay attention to the existence of anatomical dead space for accurate diagnosis . Continuous measurement is important in the collection of end tidal expired gas in order to make an accurate diagnosis.

Ann Ital Med Int, 1999 Oct-Dec, 14(4), 253 - 63
{Chlamydia pneumoniae and atherosclerosis}; Fortini A et al.; There is widespread consensus that atherosclerosis is an inflammatory disease . Between possible pathogenetic mechanisms, infective hypothesis has received increasing attention . Researches have recently focused their attention on the role of Chlamydia pneumoniae, a gram-negative intracellular organism, as infection by this bacterium has been demonstrated frequently associated with atherosclerosis . This review attempts to analyze and critically evaluate available data of the literature about the association between Chlamydia pneumoniae and atherosclerosis in order to provide updated elements of judgement concerning a possible future revolutionary scenario: the consideration of atherosclerosis as an infective disease, susceptible to prevention and treatment by means of antimicrobial therapy . More than twenty sero-epidemiological studies have found a two-fold or greater risk of cardiovascular events in subjects with serological evidence of Chlamydia pneumoniae infection . The organism has been identified in over 50% of atherosclerotic plaques examined by various histopathological techniques, while it has been only rarely found in normal artery tissues; moreover, viable Chlamydia pneumoniae has recently been isolated from coronary and carotid atherosclerotic plaques . Several experimental studies have shown that the biological properties of Chlamydia pneumoniae can explain its potential role in initiating and/or modulating plaque formation . The most relevant issue, i.e . the possibility of preventing or slowing progression of the disease with antimicrobial treatment, is still unsolved: only data from experimental studies on animals and four small intervention trials on humans are available, and their encouraging results require confirmation in larger prospective studies . In conclusion, while the association between Chlamydia pneumoniae and atherosclerosis seems to be established, it is still uncertain whether or not the organism plays a causal role in atherosclerosis and its complications . It is hoped that the results of wide scale clinical intervention trials with antibiotics for the secondary prevention of atherosclerotic diseases now in progress will clarify this problem.

J Biol Chem, 2000 Jan 21, 275(3), 2071 - 9
Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells; Kim YS et al.; Eukaryotic organisms use a similar Rel/NF-kappaB signaling cascade for the induction of innate immune genes . In Drosophila, lipopolysaccharide (LPS) signal-induced activation of the Rel/NF-kappaB family transcription factors is an essential step in the transcriptional activation of inducible antimicrobial peptide genes . However, the mechanism by which the LPS-induced signaling pathway proceeds remains largely unknown . Here we have cloned a novel Drosophila LPS-activated kinase (DLAK) that is structurally related to mammalian IkappaB kinases . DLAK is expressed and transiently activated in LPS-responsive Drosophila cells following LPS stimulation . Furthermore, DLAK can interact with Cactus, a Drosophila IkappaB and phosphorylate recombinant Cactus, in vitro . Overexpression of dominant-negative mutant DLAK (DLAK(K50A)) blocks LPS-induced Cactus degradation . DLAK-bound Cactus can be degraded in a LPS signal-dependent fashion, whereas the DLAK(K50A) mutant-bound Cactus is completely resistant to degradation in the presence of LPS . The DLAK(K50A) mutant also inhibits nuclear kappaB binding activity and kappaB-dependent diptericin reporter gene activity in a dose-dependent manner, but the kappaB-dependent diptericin reporter gene activity can be rescued by overexpression of wild type DLAK . Moreover, mRNA analysis of various kappaB-dependent antimicrobial peptide genes shows that LPS inducibility of these genes is greatly impaired in cells overexpressing DLAK(K50A) . These results establish that DLAK is a novel LPS-activated kinase, which is an essential signaling component for the induction of antimicrobial peptide genes following LPS treatment in Drosophila cells.

Acta Pol Pharm, 1999 May-Jun, 56(3), 207 - 10
Synthesis and antimicrobial activity of bis{6-phenyl-4-methyl-3-substituted-pyrazo{4,5-d} pyrazol-1-yl}thioketones; Chande MS et al.; New bis{6-phenyl-4-methyl-3-substituted-pyrazo{4,5-d} pyrazol-1-yl}thioketones have been obtained in good yield by the reaction of thiocarbohydrazine with 1-phenyl-3-methyl-4-acetyl/benzoyl-pyrazol-5-one, followed by cyclization of the intermediate . The new compounds exhibit excellent antimicrobial activity.

Neonatal Netw, 1999 Jun, 18(4), 15 - 27
Neonatal skin care: the scientific basis for practice; Lund C et al.; OBJECTIVE: To review the literature addressing the care of neonatal skin . DATA SOURCES: Computerized searches in MEDLINE and CINAHL, as well as references cited in articles reviewed . Key concepts in the searches included neonatal skin differences; neonatal skin and care practices for skin integrity; neonatal skin and toxicity; permeability; and contact irritant sensitization . STUDY SELECTION: Articles and comprehensive works relevant to key concepts and published after 1963, with an emphasis on new findings from 1993 to 1999 . One hundred two citations were identified as useful to this review . DATA EXTRACTION: Data were extracted and organized under the following headings: anatomy and physiology of the skin; physiologic and anatomic differences in neonatal skin; nutritional deficiencies; skin care practices; and care of skin breakdown . DATA SYNTHESIS: Newborns' skin is at risk for disruption of normal barrier function because of trauma . In light of available evidence about differences in neonatal skin development, clinical practice guidelines are suggested for baths, lubrication, antimicrobial skin disinfection, and adhesive removal . In addition, basic care practices are suggested for maintaining skin integrity, reducing exposure to potentially toxic substances, and promoting skin health beyond the neonatal period . Preventive care recommendations are made for reducing trauma, protecting the skin's immature barrier function, and promoting skin integrity . CONCLUSIONS: This review generated evidence with which to create a new and comprehensive practice guideline for clinicians . Evaluation of the guideline is under way at 58 U.S . sites.

J Dent Hyg, 1999 Spring, 73(2), 84 - 92
A new horizon for the dental hygienist: controlled local delivery of antimicrobials; Killoy WJ et al.; All drugs and controlled local delivery systems must be approved by the Food and Drug Administration (FDA) prior to being marketed and used in clinical practice . These systems can only be used in the clinical office setting by the dentist or under his/her supervision . One controlled local antimicrobial delivery system, tetracycline fiber, has been on the market for several years . A second system, chlorhexidine chip, was approved by the FDA in May 1998, and a third system, doxycycline polymer, was approved in September 1998 . Local delivery of antimicrobials will significantly change the way periodontitis is treated . Dental hygienists may be key therapists in providing this therapy . This article discusses the science and techniques of the three systems: tetracycline fiber, doxycycline polymer, and chlorhexidine chip . The dental hygienist's role in providing local delivery treatment is stressed . Factors important in selecting the most suitable delivery system are also discussed . This article represents a large portion of the presentation, "The Local Delivery of Antimicrobials in the Treatment of Periodontitis," made at the annual session of the American Dental Hygienists' Association (ADHA) June 27 and 28, 1998.

Eur J Biochem, 2000 Jan, 267(2), 370 - 8
Phylloxin, a novel peptide antibiotic of the dermaseptin family of antimicrobial/opioid peptide precursors; Pierre TN et al.; A novel family of peptide precursors that have very similar N-terminal preprosequences followed by markedly different C-terminal domains has been identified in the skin of hylid frogs belonging to the genus Phyllomedusinae . Biologically active peptides derived from the variable domains include the dermaseptins, 28-34-residue peptides that have a broad-spectrum microbicidal activity, and dermorphin and the deltorphins, D-amino acid containing heptapeptides that are very potent agonists for the micro-opioid and delta-opioid receptors, respectively . This report describes the isolation, synthesis and cloning of phylloxin, a prototypical member of a novel family of antimicrobial peptides derived from the processing of a dermaseptin/dermorphin-like precursor . The structure of phylloxin (GWMSKIASGIGTFLSGIQQ amide) shows no homology to the dermaseptins, but bears some resemblance to the levitide-precursor fragment and the xenopsin-precursor fragment, two antimicrobial peptides isolated from the skin of an evolutionarily distant frog species, Xenopus laevis . Circular dichroism spectra of phylloxin in low polarity medium, which mimics the lipophilicity of the membrane of target microorganisms, indicated 60-70% alpha-helical conformation, and predictions of secondary structure suggested that the peptide can be configured as an amphipathic helix spanning residues 1-19 . Phylloxin is an addition to the structurally and functionally diverse peptide families encoded by the rapidly evolving C-terminal domains of the dermorphin/dermaseptin group of precursors.

Bioorg Med Chem, 1999 Nov, 7(11), 2457 - 64
Synthesis, and cytotoxic activity of some novel indolo{2,3-b}quinoline derivatives: DNA topoisomerase II inhibitors; Kaczmarek L et al.; A series of new 5H-indolo{2,3-b}quinoline derivatives bearing methoxy and methyl groups at C-2 and C-9 was synthesized (according to the modified Graebe-Ullmann reaction) . These compounds were evaluated for their antimicrobial and cytotoxic activity and tested as inhibitors of DNA topoisomerase II . Lipophilic and calf thymus DNA binding properties of these compounds were also established . In the SAR studies we used quantum-mechanical methodology to analyze the molecular properties of the drugs . All of the 5H-indolo{2,3-b}quinolines tested were found to inhibit the growth of gram-positive bacteria and pathogenic fungi at MIC ranging between 2.0 and 6.0 microM . They showed also cytotoxic activity in vitro against several human cancer cell lines of different origin (ID50 varied from 0.6 to 1.4 microM), and stimulated the formation of topoisomerase-II-mediated pSP65 DNA cleavage at concentration between 0.2 and 0.5 microM . The most active indolo{2,3-b}quinolines which had the greatest contribution to the increase in the Tm of DNA displayed also the highest DNA binding constants and the highest cytotoxic activity . The differences in DNA binding properties and cytotoxic activity seem to be more related to steric than electrostatic effects.

Pharmazie, 1999 Dec, 54(12), 879 - 84
Antimicrobial activity of substituted azoles and their nucleosides; Stefanska JZ et al.; Four new 2'-deoxynucleosides of benzimidazole derivatives were prepared . Antimicrobial activity of many indazole, benzotriazole, benzimidazole derivatives and their nucleosides were tested by the agar diffusion method . Among the investigated compounds, dinitro- and trifluoromethyl-substituted benzimidazoles and their nucleosides were the most potent.

Biochim Biophys Acta, 2000 Jan 15, 1463(1), 55 - 64
Origin of antibacterial stasis by polymyxin B in Escherichia coli; Liechty A et al.; We show that blockage of hyperosmotic shock induced plasmolysis by polymyxin B (PxB) is related to its selective antimicrobial action against Gram-negative organisms . The rapid wrinkling of the cytoplasmic membrane induced by the hyperosmotic shrinkage of cytoplasmic volume due to the water efflux is monitored as an increase in the 90 degrees light scattering . The rapid scattering response is complete within 1 min after the addition of hyperosmolar NaCl . PxB decreases the amplitude of the rapid increase in the light scattering due to the shrinkage of the cytoplasmic volume by hyperosmotic shock . The amplitude is highest with cells in the early log phase of growth . The effect of PxB is induced rapidly and the maximum effect is seen within 1 min preincubation of cells . The effect of PxB is concentration dependent, and about 50% decrease in the amplitude is seen in the range of the growth inhibitory concentrations of PxB . The effect of PxB is not seen if added after the onset of the up-shock . As a heuristic model we suggest that PxB forms contacts between the two phospholipid interfaces that enclose the periplasmic space . The plasmolytic response results with osmY(-) mutant suggest that, like PxB, the osmY gene product in the periplasmic space prevents the shrinkage of the cytoplasmic compartment . Since PxB induces osmY transcription, we propose that, as a possible locus for the origin of the PxB induced stress, a contact between the phospholipid interfaces surrounding the periplasmic space triggers the metabolic changes leading to bacterial stasis.

Biochim Biophys Acta, 2000 Jan 15, 1463(1), 43 - 54
Cationic peptide antimicrobials induce selective transcription of micF and osmY in Escherichia coli; Oh JT et al.; Cationic antimicrobial peptides, such as polymyxin and cecropin, activated transcription of osmY and micF in growing Escherichia coli independently of each other . The micF response required the presence of a functional rob gene . It is intriguing that in this and other assays an identical response profile was also seen with hyperosmotic salt or sucrose gradient, two of the most commonly used traditional food preservatives . The osmY and micF transcription was not induced by hypoosmotic gradient, ionophoric peptides, uncouplers, or with other classes of membrane perturbing agents . The antibacterial peptides did not promote transcription of genes that respond to macromolecular or oxidative damage, fatty acid biosynthesis, heat shock, or depletion of proton or ion gradients . These and other results show that the antibacterial cationic peptides induce stasis in the early growth phase, and the transcriptional efficacy of antibacterial peptides correlates with their minimum inhibitory concentration, and also with their ability to mediate direct exchange of phospholipids between vesicles . The significance of these results is developed as the hypothesis that the cationic peptide antimicrobials stress growth of Gram-negative organisms by making contacts between the two phospholipid interfaces in the periplasmic space and prevent the hyperosmotic wrinkling of the cytoplasmic membrane . Broader significance of these results, and of the hypothesis that the peptide mediated contacts between the periplasmic phospholipid interfaces are the primary triggers, is discussed in relation to antibacterial resistance.

Cornea, 2000 Jan, 19(1), 34 - 9
Management of infectious scleritis after pterygium excision; Huang FC et al.; PURPOSE: We sought to describe the clinical features, responsible pathogens, management, and prognosis of infectious scleritis after pterygium excision . METHODS: A retrospective study through review of medical records of patients diagnosed with infectious scleritis after pterygium excision over a 10-year period at our institution . RESULTS: A total of 16 cases of infectious scleritis after pterygium excision was identified . Among them, eight were associated with sclerokeratitis, and six had multifocal scleral nodules with subconjunctival abscesses . Culture results were positive in 15 (93.8%) cases . Pseudomonas was isolated in 13 (81.3%) patients, fungus in three (18.8%), and two had a mixed growth (12.5%) . Based on the in vitro susceptibility test, four (31%) Pseudomonas isolates were resistant to gentamicin, whereas all isolates were sensitive to amikacin . During the course of treatment, eight cases were complicated by vitreous opacity, four developed glaucoma, four had serous retinal or choroidal detachment, and two had secondary cataract . Scleral infection recurred in two patients after cessation of therapy . Among the nine patients treated with medical therapy, two eyes were enucleated, whereas only two attained a visual acuity of > or =2/200 at the end of the follow-up period . On the other hand, seven patients had combined antibiotic therapy and surgical debridement . The number of surgical debridement ranged from one to three, with an average of 1.4 . In this combined-treatment group, only one patient required enucleation, and five cases attained a visual acuity of > or =2/200 . The duration of hospitalization for patients with combined treatment was 21.2+/-4.8 days compared with the 28.4+/-5.0 days for those with medical treatment alone (p = 0.035) . CONCLUSION: Surgical debridement in combination with appropriate antimicrobial therapy shortens the course of treatment and improves the visual outcome of severe infectious scleritis after pterygium excision.

Planta Med, 1999 Dec, 65(8), 752 - 4
Chemical composition and antimicrobial action of the essential oils of Salvia desoleana and S . sclarea; Peana AT et al.; The chemical composition of the essential oils of Salvia desoleana Atzei & Picci and Salvia sclarea L . from Sardinia (Italy) was analysed by GC and GC/MS . S . desoleana oil had a high content of monoterpenic esters (linalyl acetate and alpha-terpinyl acetate) and a lower amount of the corresponding alcohols while S . sclarea oil was characterised by a higher content of alcohols and lower quantity of esters . We studied the antimicrobial activity of these oils concerning their use in pharmaceutical preparations for local application . Only weak microbiostatic inhibitory activity was seen against S . aureus, E . coli, S . epidermidis and C . albicans, but since inhibition increased progressively with contact time, better results could be obtained by using these oils in bioadhesive formulations that would also have anti-inflammatory and peripheral analgesic action at a local level, as demonstrated in experimental animals following systemic application.

Planta Med, 1999 Dec, 65(8), 749 - 52
Chemical composition and antimicrobial activity of the essential oils of Pistacia lentiscus var . chia; Magiatis P et al.; The chemical composition of the three essential oils obtained by steam distillation of the mastic gum, leaves and twigs of Pistacia lentiscus var . chia, was studied by GC/MS . Sixty nine constituents were identified from the oils . alpha-Pinene, myrcene, trans-caryophyllene and germacrene D were found to be the major components . The in vitro antimicrobial activity of the three essential oils and of the resin (total, acid and neutral fraction) against six bacteria and three fungi is reported.

Planta Med, 1999 Dec, 65(8), 735 - 9
Analysis of labdane-type diterpenes from Cistus creticus (subsp . creticus and subsp . eriocephalus), by GC and GC-MS; Anastasaki T et al.; The qualitative and quantitative analysis of labdane-type diterpenes of the hexane extracts and of the essential oils of the leaves, fruits and resin "Ladano", of Cistus creticus subsp . creticus and Cistus creticus subsp . eriocephalus, have been carried out by GC and GC-MS analysis using two capillary chromatographic columns, i.e., HP-5MS and CP-Wax . The methanolic extract of the fruits of C . creticus subsp . creticus was examined and seven labdane diterpenes were isolated and identified by spectroscopic methods . Data on the investigation of labdane diterpenes by GC and GC-MS is limited and most of them have never been analysed by this method . The results obtained by this analysis could be useful for identifying them in crude plant extracts . Manoyl oxides were studied further for the percentage content of their isomers . The hexane extracts of the two subspecies as well as the manoyl oxide isomers isolated from the methanolic extract of the fruits of C . creticus subsp . creticus, were tested for their antimicrobial activity against Gram-positive and Gram-negative bacteria . Global numerical differences of these C . creticus subspecies, based on labdane diterpenes content in the hexane extracts as well as in the essential oils, were established by statistical methods . Phenotypic differences are discussed.

J Allergy Clin Immunol, 2000 Jan, 105(1 Pt 1), 39 - 44
Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? A cautionary note based on compromised mucociliary transport; Bernstein IL; BACKGROUND: Topical nasal solution and suspension delivery systems are available for short- and long-acting vasoconstrictors, ipratropium, cromolyn, azelastine, and glucocorticosteroids . The use of intranasal glucocorticosteroids has increased substantially because the efficacy of these agents has been well established for the treatment of perennial and seasonal allergic rhinitis . Adverse local effects of burning, irritation, and dryness are occasionally associated with glucocorticosteroid nasal preparations . Benzalkonium chloride (BKC) is a quaternary ammonium antimicrobial agent included in some nasal solutions (including glucocorticosteroids) to prevent the growth of bacteria . Some reports suggest that BKC in nasal sprays may cause adverse effects, including reduced mucociliary transport, rhinitis medicamentosa, and neutrophil dysfunction . OBJECTIVE: This article summarizes recent literature about possible adverse biologic effects associated with BKC as a nasal spray preservative by examining its effects on the following properties of mucociliary transport: ciliary motion, ciliary form, ciliary beat frequency, electron microscopy, and particle movement/saccharin clearance tests . CONCLUSION: Both animal and human in vitro data suggest that BKC promotes ciliostasis and reduction in mucociliary transport that may be partially masked by absorption and dilution effects occurring in respiratory mucus . These possible confounding factors may account for several disparate human in vivo results . The use of BKC-free glucocorticosteroid formulations should be considered, particularly in patients who complain of nasal burning, dryness, or irritation.

Nutrition, 2000 Nov-Dec, 16(11-12), 1090 - 2
Abnormal liver functions as a result of total parenteral nutrition in a patient with short-bowel syndrome; Burstyne M et al.; The pathogenesis of total parenteral nutrition (TPN)-induced liver cholestasis is poorly understood . Cholestasis generally occurs late in TPN therapy in association with elevated serum alkaline phosphatase and total bilirubin concentrations . Such factors as preexisting medical conditions, excessive nutrient infusion, amino-acid deficiency, absence of enteral stimulation, protracted duration of therapy, continuous infusion schedule, and hypoalbuminemia have all been suggested as possible etiologies . Various treatments have been proposed for the correction of TPN-induced cholestasis including administration of bile salt and antimicrobial therapies . To avoid potential hepatic complications associated with TPN, certain preventive measures can be considered . Administration of energy substrates should not be excessive . A mixed-fuel system that includes lipids should be implemented . TPN should be cycled if it will be used long term, and initiation of enteral nutrition should begin as soon as possible.

Biochem Biophys Res Commun, 2000 Dec 20, 279(2), 574 - 81
Expression and evolution of the Drosophila attacin/diptericin gene family; Hedengren M et al.; We describe the genes for three new glycine-rich antimicrobial peptides in Drosophila, two attacins (AttC and AttD) and one diptericin (DptB) . Their structures support the proposal that these glycine-rich antimicrobial peptides evolved from a common ancestor and are probably also related to proline-rich peptides such as drosocin . AttC is similar to the nearby AttA and AttB genes . AttD is more divergent and located on a different chromosome . Intriguingly, AttD may encode an intracellular attacin . DptB is linked in tandem to the closely related Diptericin . However, the DptB gene product contains a furin-like cleavage site and may be processed in an attacin-like fashion . All attacin and diptericin genes are induced after bacterial challenge . This induction is reduced in imd mutants, and unexpectedly also in Tl(-) mutants . The 18w mutation particularly affects the induction of AttC, which may be a useful marker for 18w signaling .

J Antimicrob Chemother, 2000 Jan, 45(1), 115 - 7
Levofloxacin in vitro activity and time-kill evaluation of Stenotrophomonas maltophilia clinical isolates; Bonfiglio G et al.; The in vitro activity of levofloxacin and eight other antimicrobial agents against 60 clinical isolates of Stenotrophomonas maltophilia was determined by an agar dilution method using 10(4) and 10(6) cfu/spot inocula . At the lower inoculum, 85.0% of the isolates were susceptible to levofloxacin but only 58.3% were susceptible to ofloxacin; at the higher inoculum, 78.3% were susceptible to levofloxacin and 36.7% to ofloxacin . In time-kill studies, levofloxacin exerted bactericidal activity within 4 h . With ofloxacin and ciprofloxacin bacterial regrowth was observed after 8 h . Levofloxacin may represent an alternative drug in the treatment of infections caused by S . maltophilia.

J Antimicrob Chemother, 2000 Jan, 45(1), 15 - 25
Sub-MIC concentrations of cefodizime interfere with various factors affecting bacterial virulence; Braga PC et al.; The molecular array of the outermost surface of bacteria and their physico-chemical characteristics modulate various functions which, when expressed in terms of the human environment, are generally known as factors of bacterial virulence . The present study investigated the ability of sub-MIC concentrations of cefodizime to interfere with the virulence factors of Escherichia coli . Bacterial adhesiveness to human epithelial cells was inhibited down to 1/32 x MIC of cefodizime, an antibiotic that is also capable of inducing the widespread production of filamentous forms at levels ranging from 1/2 to 1/8 x MIC . Given that this interfered with the correct evaluation of other virulence parameters, the study was extended to consider the effects of 1/16 to 1/128 x MIC . Sub-MIC concentrations of cefodizime inhibit haemagglutination, hydrophobicity and electrophoretic mobility, which are correlated with each other and provide clues relating to the physico-chemical characteristics of the outer surface . Cefodizime also reduces swarming . Phagocytosis was not affected but killing increased significantly . Oxidative bursts investigated by a chemiluminescence procedure were not modified . The interpolation of these pharmacodynamic findings with pharmacokinetic curves indicates that the effect of sub-MIC concentrations of cefodizime can prolong antimicrobial effects on virulence determinants up to 12 h after the antibiotic concentration has fallen below the MIC value.

Lik Sprava, 1999 Sep, (6), 110 - 4
{The effect of the application sorption of a fibrous activated charcoal material with highly dispersed iron on the course of a wound process}; Symorot MI et al.; Results of the experiments carried out show that the use of the activated carbon fibrous material "Dnipro" for medical purposes (ABBM "Dnipro" MP) and the suspension of high-dispersity iron combined in treatment of infected and suppurating wounds is associated with a more pronounced therapeutical effect than application to the wound surfaces of the standard ABBM "Dnipro" MP . The compositional method using ABBM "Dnipro" MP and high-dispersity iron obtainable by thermochemical techniques has a marked antimicrobial action and stimulates the course of the wound process.

Lik Sprava, 1999 Sep, (6), 107 - 10
{Current approaches to the topical treatment of acne vulgaris}; Vovk OB; Data are submitted from the published literature on the application of different groups of topicals in the treatment of acne vulgaris . The mechanism of action of keratolytic and antimicrobial agents intended for external use is described . Certain main principles of treatment of mild to moderately severe acne vulgaris are formulated.

Plast Reconstr Surg, 2000 Jan, 105(1), 62 - 5
Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns; Barret JP et al.; Partial-thickness burns in children have been treated for many years by daily, painful tubbing, washing, and cleansing of the burn wound, followed by topical application of antimicrobial creams . Pain and impaired wound healing are the main problems . We hypothesized that the treatment of second-degree burns with Biobrane is superior to topical treatment . Twenty pediatric patients were prospectively randomized in two groups to compare the efficacy of Biobrane versus 1% silver sulfadiazine . The rest of the routine clinical protocols were followed in both groups . Demographic data, wound healing time, length of hospital stay, pain assessments and pain medication requirements, and infection were analyzed and compared . Main outcome measures included pain, pain medication requirements, wound healing time, length of hospital stay, and infection . The application of Biobrane to partial-thickness burns proved to be superior to the topical treatment . Patients included in the biosynthetic temporary cover group presented with less pain and required less pain medication . Length of hospital stay and wound healing time were also significantly shorter in the Biobrane group . None of the patients in either group presented with wound infection or needed skin autografting . In conclusion, the treatment of partial-thickness burns with Biobrane is superior to topical therapy with 1% silver sulfadiazine . Pain, pain medication requirements, wound healing time, and length of hospital stay are significantly reduced.

Rev Prat, 1999 Nov 15, 49(18), 2009 - 13
{Infectious uveitis}; Guerzider V et al.; Half a century ago, bacterial diseases such as tuberculosis and syphilis were thought to cause the majority of cases of uveitis . Nowadays, a number of infectious diseases are responsible for uveitis . In our countries, herpes virus and toxoplasmosis are the principal causes of uveitis . Furthermore, because specific antimicrobial therapy can be curative and prevent long-term visual sequel, early diagnosis of infectious causes of uveitis should be a priority for all practitioners.

Surg Clin North Am, 1999 Dec, 79(6), 1471 - 88
Prevention of multiple organ failure; Deitch EA et al.; Physicians are still largely ignorant of the underlying biology of SIRS and multiple organ failure . Nonetheless, strategies to prevent multiple organ failure are possible . These include aggressive resuscitation of hemodynamically unstable patients, careful assessment to avoid missing clinically significant injuries, early operative treatment of all possible injuries with debridement of all nonviable tissue, early nutritional support, and the early diagnosis and prompt treatment of infectious complications . Treatment of patients with established multiple organ failure is still largely supportive and has made little impact on the patient mortality rate over the past 20 years . Future treatment strategies must focus on multimodality combination therapy aimed at specifically suppressing excessive activation of the inflammatory response while preserving immune competence and normal antimicrobial defenses . Only then are physicians likely to begin to see a reduction in the mortality rate of patients with this complex and challenging condition.

Biochemistry, 2000 Jan 11, 39(1), 139 - 45
Membrane thinning effect of the beta-sheet antimicrobial protegrin; Heller WT et al.; Lipid bilayers containing the antimicrobial peptide protegrin-1 (PG-1) were studied by lamellar X-ray diffraction . Previously, we have shown that the peptide exists in two distinct states when associated with lipid bilayers depending on the peptide concentration {Heller, W . T., Waring, A . J., Lehrer, R . I., and Huang, H . W . (1998) Biochemistry 37, 17331-17338} . For concentrations below a lipid-dependent threshold, PG-1 exhibits a unique oriented circular dichroism spectrum called the S state . X-ray experiments show that in this state PG-1 decreases the thickness of the lipid bilayer in proportion to the peptide concentration, similar to alamethicin's membrane thinning effect . This indicates that the S state is adsorbed in the headgroup region of the lipid bilayer, where the peptide is in an inactive state . For PG-1 above the threshold concentration, X-ray diffraction shows that the interaction between the peptide and the bilayer changes significantly . These results suggest that PG-1 has the same concentration-gated mechanism of action as alamethicin.

J Ethnopharmacol, 1999 Dec 15, 68(1-3), 115 - 20
Evaluation of the genotoxic potential of the isocoumarin paepalantine in in vivo and in vitro mammalian systems; Tavares DC et al.; Paepalantine is an isocoumarin isolated from Paepalanthus vellozioides which showed antimicrobial activity in in vitro experiments . In the present study, paepalantine was tested for possible clastogenic and cytotoxic action . Cultures from different individuals were treated with paepalantine at concentrations of 20, 40 and 80 microg/ml . The effect of isocoumarin was also tested in an in vivo assay using Wistar rat bone marrow cells . Paepalantine was administered intraperitoneally at concentrations of 6.25, 12.5 and 25 mg/kg body weight . Under these conditions paepalantine did not have a clastogenic effect, but was significantly cytotoxic in the in vitro and in vivo mammalian cell systems tested in the present work.

J Mol Biol, 2000 Jan 14, 295(2), 307 - 23
Three-dimensional structure of M . tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs; Li R et al.; Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate and is essential for the synthesis of thymidylate, purines and several amino acids . Inhibition of the enzyme's activity leads to arrest of DNA synthesis and cell death . The enzyme has been studied extensively as a drug target for bacterial, protozoal and fungal infections, and also for neoplastic and autoimmune diseases . Here, we report the crystal structure of dihydrofolate reductase from Mycobacterium tuberculosis, a human pathogen responsible for the death of millions of human beings per year . Three crystal structures of ternary complexes of M . tuberculosis DHFR with NADP and different inhibitors have been determined, as well as the binary complex with NADP, with resolutions ranging from 1.7 to 2.0 A . The three DHFR inhibitors are the anticancer drug methotrexate, the antimicrobial trimethoprim and Br-WR99210, an analogue of the antimalarial agent WR99210 . Structural comparison of these complexes with human dihydrofolate reductase indicates that the overall protein folds are similar, despite only 26 % sequence identity, but that the environments of both NADP and of the inhibitors contain interesting differences between the enzymes from host and pathogen . Specifically, residues Ala101 and Leu102 near the N6 of NADP are distinctly more hydrophobic in the M . tuberculosis than in the human enzyme . Another striking difference occurs in a region near atoms N1 and N8 of methotrexate, which is also near atom N1 of trimethoprim, and near the N1 and two methyl groups of Br-WR99210 . A glycerol molecule binds here in a pocket of the M . tuberculosis DHFR:MTX complex, while this pocket is essentially filled with hydrophobic side-chains in the human enzyme . These differences between the enzymes from pathogen and host provide opportunities for designing new selective inhibitors of M . tuberculosis DHFR .

J Immunol, 2000 Jan 15, 164(2), 549 - 53
Cutting edge: cationic antimicrobial peptides block the binding of lipopolysaccharide (LPS) to LPS binding protein; Scott MG et al.; We investigated the mechanism by which cationic antimicrobial peptides block the activation of macrophages by LPS . The initial step in LPS signaling is the transfer of LPS to CD14 by LPS binding protein (LBP) . Because many cationic antimicrobial peptides bind LPS, we asked whether these peptides block the binding of LPS to LBP . Using an assay that measures the binding of LPS to immobilized LBP, we show for the first time that a variety of structurally diverse cationic antimicrobial peptides block the interaction of LPS with LBP . The relative ability of different cationic peptides to block the binding of LPS to LBP correlated with their ability to block LPS-induced TNF-alpha production by the RAW 264.7 macrophage cell line.

FEBS Lett, 1999 Dec 3, 462(3), 273 - 7
Permeabilizing action of an antimicrobial lactoferricin-derived peptide on bacterial and artificial membranes; Aguilera O et al.; A synthetic peptide (23 residues) that includes the antibacterial and lipopolysaccharide-binding regions of human lactoferricin, an antimicrobial sequence of lactoferrin, was used to study its action on cytoplasmic membrane of Escherichia coli 0111 and E . coli phospholipid vesicles . The peptide caused a depolarization of the bacterial cytoplasmic membrane, loss of the pH gradient, and a bactericidal effect on E . coli . Similarly, the binding of the peptide to liposomes dissipated previously created transmembrane electrical and pH gradients . The dramatic consequences of the transmembrane ion flux during the peptide exposure indicate that the adverse effect on bacterial cells occurs at the bacterial inner membrane.

Int J Clin Pract, 1998 Oct, 52(7), 456 - 60
Skin and soft tissue infections: development of a collaborative management plan between community and hospital care; Nathwani D et al.; The commonest indication in the US for referral to an outpatient/home i.v . antibiotic therapy programme is the management of skin and soft tissue infections . In the UK, however, these infections account for 10% or more of admissions to infection units . The main indication for hospitalisation is to receive parenteral antibiotics . A retrospective audit of one year of admissions to a regional infection unit revealed that, although most of these patients do not progress to complications ('low risk'), they occupy a mean time of five days in hospital and for nearly half of that time they receive parenteral antibiotics . This period in hospital reflected 11.4% of the unit's bed occupancy . Even if 75% of these patients were treated in the community with parenteral therapy, this would result in bed savings of 8.55%, nearly one-tenth of the unit's occupied capacity . This type of audit should help key decision makers thinking of developing similar services in their region . Outpatient or home parenteral antimicrobial therapy (OHPAT) should be delivered as part of a complete disease management programme in collaboration with primary care.

Clin Infect Dis, 2000 Jan, 30(1), 166 - 73
Detection of selected fastidious bacteria; Doern GV; The intent of this article is to describe the optimal methods for culture recovery of 7 fastidious bacteria: Legionella species, Brucella species, Francisella tularensis, Leptospira species, Borrelia burgdorferi, Bartonella species, and Bordetella species . These organisms share much in common beyond the fact that their genus names all end in the letter "a." Culture recovery of these organisms, even from adequate clinical specimens, is logistically demanding, often costly, and lacking in both timeliness and sensitivity . In addition, there is generally no need to recover culture isolates on which to perform antimicrobial susceptibility tests because these 7 bacteria are nearly uniformly susceptible to specific, clinically useful antimicrobial agents and because, for some of them, susceptibility tests of proven reliability have not yet been devised . Perhaps for these reasons, alternative, more rapid, direct diagnostic approaches have been developed that are based on either immunochemical or nucleic-acid detection methods . These methods have generally served to supplant culture as a primary diagnostic modality . Situations exist, however, in which culture may be desirable, if not necessary, to establish a definitive diagnosis of infection with these 7 organisms . This review attempts to summarize how best to proceed in those cases.

J Ethnopharmacol, 1999 Nov 1, 67(2), 241 - 5
Phytotoxic and antimicrobial constituents of Argyreia speciosa and Oenothera biennis; Shukla YN et al.; The antifungal activity of hexadecanyl p-hydroxycinnamate (1), scopoletin (2) isolated from Argyreia speciosa roots and gallic acid (3) from Oenothera biennis roots was evaluated against three fungi . Compound 1 and 2 were found to be highly potent against Alternaria alternata compared to 3 . The phytotoxicity in terms of root growth inhibition of germinating wheat seeds was observed in all the three test materials . At 250 ppm concentration the inhibition caused by 3, was 85.63%; 1, 79.42%; and 2, 91.57% . At higher concentrations (1000 ppm) the root growth of the wheat was completely inhibited . The structures of these compounds were established using spectral and chemical methods.

J Clin Microbiol, 2000 Jan, 38(1), 158 - 64
Identification of nocardia species by restriction endonuclease analysis of an amplified portion of the 16S rRNA gene; Conville PS et al.; Identification of clinical isolates of Nocardia to the species level is important for defining the spectrum of disease produced by each species and for predicting antimicrobial susceptibility . We evaluated the usefulness of PCR amplification of a portion of the Nocardia 16S rRNA gene and subsequent restriction endonuclease analysis (REA) for species identification . Unique restriction fragment length polymorphism (RFLP) patterns were found for Nocardia sp . type strains (except for the N . asteroides type strain) and representative isolates of the drug pattern types of Nocardia asteroides (except for N . asteroides drug pattern type IV, which gave inconsistent amplification) . A variant RFLP pattern for Nocardia nova was also observed . Twenty-eight clinical isolates were evaluated both by traditional biochemical identification and by amplification and REA of portions of the 16S rRNA gene and the 65-kDa heat shock protein (HSP) gene . There was complete agreement among the three methods on identification of 24 of these isolates . One isolate gave a 16S rRNA RFLP pattern consistent with the biochemical identification but was not identifiable by its HSP gene RFLP patterns . Three isolates gave 16S rRNA RFLP patterns which were inconsistent with the identification obtained by both biochemical tests and HSP gene RFLP; sequence analysis suggested that two of these isolates may belong to undefined species . The PCR and REA technique described appears useful both for the identification of clinical isolates of Nocardia and for the detection of new or unusual species.

J Clin Microbiol, 2000 Jan, 38(1), 79 - 84
Heterogeneity of Actinobacillus actinomycetemcomitans strains in various human infections and relationships between serotype, genotype, and antimicrobial susceptibility; Paju S et al.; Actinobacillus actinomycetemcomitans, an oral pathogen, only occasionally causes nonoral infections . In this study 52 A . actinomycetemcomitans strains from 51 subjects with nonoral infections were serotyped and genotyped by arbitrarily primed PCR (AP-PCR) to determine whether a certain clone(s) is specifically associated with nonoral infections or particular in vitro antimicrobial susceptibility patterns . The promoter structure of leukotoxin genes was additionally investigated to find the deletion characteristic of highly leukotoxic A . actinomycetemcomitans strains . The nonoral A . actinomycetemcomitans strains included all five known serotypes and nonserotypeable strains, the most common serotypes being b (40%) and c (31%) . AP-PCR distinguished 10 different genotypes . A . actinomycetemcomitans serotype b strains were more frequently found in blood samples of patients with bacteremia or endocarditis than in patients with focal infections . One AP-PCR genotype was significantly more frequently found among strains originating in focal infections than in blood samples . Resistance to benzylpenicillin was significantly more frequent among A . actinomycetemcomitans serotype b strains than among strains of other serotypes . No differences in the leukotoxin gene promoter region or benzylpenicillin resistance between nonoral and oral A . actinomycetemcomitans strains were observed . Nonoral A . actinomycetemcomitans strains showed great similarity to the oral strains, confirming that the oral cavity is the likely source of nonoral A . actinomycetemcomitans infections . The predominance of serotype b strains in endocarditis and bacteremia supports the hypothesis of a relationship between certain A . actinomycetemcomitans clones and some nonoral infections . The mechanisms behind the exceptionally high rate of occurrence of benzylpenicillin resistance among A . actinomycetemcomitans serotype b strains are to be elucidated in further studies.

J Clin Microbiol, 2000 Jan, 38(1), 32 - 9
Direct amplification of rRNA genes in diagnosis of bacterial infections; Rantakokko-Jalava K et al.; A broad-range bacterial PCR targeting rRNA genes (rDNAs) was used to directly analyze 536 clinical samples obtained from 459 hospitalized patients during a 4-year study period . The molecular diagnosis based on DNA sequencing of the PCR product was compared to that obtained by bacterial culture . The bacteriological diagnosis was concordant for 447 (83%) specimens . Broad-range rDNA PCR was the only method that yielded an etiologic diagnosis for 11 (2.4%) of 459 patients . Compared to culture and clinical assessment, the sensitivity of the PCR method combined with sequencing was 74.2%, and the specificity was between 98.7 and 99.6% . At present, the described molecular approach proved superior to bacterial culture in two clinical situations: infections caused by bacteria with unusual growth requirements and specimens taken during antimicrobial treatment of the patient.

J Immunol Methods, 1999 Dec 17, 232(1-2), 211 - 29
Clinical and laboratory work-up of patients with neutrophil shortage or dysfunction; Kuijpers TW et al.; Neutrophils have a crucial function in the defense against bacteria and fungi . Indeed, during chronic, severe neutropenia and in case of severe neutrophil dysfunctions, the patients may suffer recurrent and sometimes life-threatening infections . This article describes the clinical symptoms, the theory behind the antimicrobial systems of neutrophils, the methods to diagnose the various aberrations, and the possibilities for treating these patients . A few of the most common causes of neutropenia and neutrophil dysfunctions are described in detail, including recent genetic information regarding the cause of these diseases.

J Immunol Methods, 1999 Dec 17, 232(1-2), 45 - 54
Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system; Gudmundsson GH et al.; The bactericidal machinery of mammalian neutrophils is built up of many components with different chemical properties, involving proteins, peptides and oxygen-dependent radicals . All these components work in synergy, leading to destruction and elimination of ingested microbes . During the eighties, it gradually became clear, that cationic peptides are a part of the oxygen-independent bactericidal effectors in phagocytic cells . In mammals, these antimicrobial peptides are represented by two families, the defensins and the cathelicidins . These potent broad spectra peptides are included as immediate effector molecules in innate immunity . The detailed killing mechanism for these effectors is partly known, but nearly all of them have membrane affinity, and permeate bacterial membranes, resulting in lysis of the bacteria . This peptide-membrane interaction includes also eukaryotic membranes, that implicates cytotoxic effects on host cells . Studies in vitro have established that the microenvironment is critical for their activities . In connection to cystic fibrosis, the effects of microenvironment changes are apparent, causing inactivation of peptide defences and leading to repeated serious bacterial infections . Thus, the importance of the microenvironment is also supported in vivo . Additional functions of these peptides such as chemotactic, mitogenic and stimulatory in the wound healing process suggest further important roles for these peptides.

Appl Environ Microbiol, 2000 Jan, 66(1), 80 - 6
Antimicrobial actions of degraded and native chitosan against spoilage organisms in laboratory media and foods; Rhoades J et al.; The objective of this study was to determine whether chitosan (poly-beta-1,4-glucosamine) and hydrolysates of chitosan can be used as novel preservatives in foods . Chitosan was hydrolyzed by using oxidative-reductive degradation, crude papaya latex, and lysozyme . Mild hydrolysis of chitosan resulted in improved microbial inactivation in saline and greater inhibition of growth of several spoilage yeasts in laboratory media, but highly degraded products of chitosan exhibited no antimicrobial activity . In pasteurized apple-elderflower juice stored at 7 degrees C, addition of 0.3 g of chitosan per liter eliminated yeasts entirely for the duration of the experiment (13 days), while the total counts and the lactic acid bacterial counts increased at a slower rate than they increased in the control . Addition of 0.3 or 1.0 g of chitosan per kg had no effect on the microbial flora of hummus, a chickpea dip; in the presence of 5.0 g of chitosan per kg, bacterial growth but not yeast growth was substantially reduced compared with growth in control dip stored at 7 degrees C for 6 days . Improved antimicrobial potency of chitosan hydrolysates like that observed in the saline and laboratory medium experiments was not observed in juice and dip experiments . We concluded that native chitosan has potential for use as a preservative in certain types of food but that the increase in antimicrobial activity that occurs following partial hydrolysis is too small to justify the extra processing involved.

J Gastroenterol, 1999, 34 Suppl 11, 76 - 9
Comparison of 1-week and 2-week triple therapy with omeprazole, amoxicillin, and clarithromycin in peptic ulcer patients with Helicobacter pylori infection: results of a randomized controlled trial; Kiyota K et al.; This study was a comparison of 1-week and 2-week triple therapies with omeprazole, amoxicillin, and clarithromycin (OAC) in patients with peptic ulcer disease and Helicobacter pylori infection . A total of 147 peptic ulcer patients with H . pylori infection assessed by histology and culture were randomly treated with omeprazole 20mg bid + amoxicillin 1000mg bid + clarithromycin 400mg bid for either 1 week (OAC1w) or 2 weeks (OAC2w) . Both groups then received omeprazole 20mg daily for 2 weeks followed by ranitidine 300mg daily for 4 weeks . Eradication of H . pylori was assessed by histology, culture, and the 13C-urea breath test (13C-UBT) at least 6 weeks after cessation of antimicrobial therapy . Intention-to-treat eradication rates were 78.2% (95%CI 69%-87%) with OAC1w and 88.4% (95%CI 81%-96%) with OAC2w . Per-protocol eradication rates were 86.0% (95%CI 78%-94%) with OAC1w, 97.0% (95%CI 93%-100%) with OAC2w . There was no significant difference in the eradication rates between OAC1w and OAC2w . Side effects were mild and self-limiting in both groups . In conclusion, both 1- and 2-week triple therapy with OAC are well tolerated and provide good eradication rates in peptic ulcer patients in Japan . The eradication rate of the 2-week regimen was higher than that of the 1-week regimen, but the difference was not statistically significant . Further studies including long-term economic considerations are required to determine the optimal duration of treatment.

Am J Respir Cell Mol Biol, 2000 Jan, 22(1), 51 - 60
Interleukin-8 gene repression by clarithromycin is mediated by the activator protein-1 binding site in human bronchial epithelial cells; Abe S et al.; Macrolide antibiotics are known to be effective for the treatment of chronic inflammatory airway diseases including diffuse panbronchiolitis, chronic bronchitis, and bronchial asthma . Other than having antimicrobial activities, macrolides have antiinflammatory effects, such as the inhibition of cytokine production . In the present study we investigated the effects of clarithromycin (CAM) on interleukin (IL)-8 gene expression and protein levels, using the human bronchial epithelial cell line BET-1A . Northern blot analyses showed that CAM inhibited tumor necrosis factor (TNF)-alpha-induced IL-8 gene expression in a dose- and incubation time-dependent manner . The half-life of IL-8 messenger RNA transcripts in TNF-alpha-treated BET-1A cells did not change with CAM . Transfection studies with BET-1A cells, using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene, demonstrated potent promoter activity in a 174-bp segment (-130 to +44 bp relative to the transcription start site) . This segment includes activator protein (AP)-1 and nuclear factor (NF)-kappaB-like sites, and exhibited its strongest response to TNF-alpha . TNF-alpha-induced promoter activity in this segment showed a significant repression by CAM . However, a 156-bp segment (-112 to +44 bp) that does not include an AP-1 site but includes an NF-kappaB-like site did not show a significant repression of TNF-alpha-induced promoter activity by CAM . Mutation of the AP-1 binding site abrogated the suppression by CAM of TNF-alpha-induced enhancement of luciferase activity . In accord with promoter analyses, an electrophoretic mobility shift assay showed that CAM repressed AP-1 binding in TNF-alpha-treated BET-1A cells; however, TNF-alpha induced both AP-1 and NF-kappaB binding activities in BET-1A cells . These data suggest that macrolides such as CAM repress IL-8 gene transcription mainly via the AP-1 binding site in human bronchial epithelial cells . Our findings provide a novel mechanism for the antiinflammatory function of macrolides, implicating a target for the development of new drugs for treating chronic airway inflammation.

Acta Odontol Scand, 1999 Oct, 57(5), 267 - 70
The limited value of three pathogen species in predicting healing of periodontal pockets; Sewon L et al.; Baseline level of Actinobacillus actinomycetemcomitans has been suggested as being predictive of periodontal treatment outcome . We analyzed the presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in 55 deep periodontal pockets of 29 patients (18 men, 11 women, 37-75 years) before and after periodontal treatment . At baseline and after treatment, 62% and 33%, respectively, of the subjects presented with 1, 2, or a combination of all 3 pathogens . The mean pocket depth of 6.6 mm (0.4 mm) before treatment decreased to 2.2 mm (0.4 mm) in response to treatment (P<0.001) . The treatment plan of non-surgical or surgical treatment was based on pocket depths and tooth morphology only . No antimicrobial medications were used during the treatment . Eighty-two percent of the deep pockets healed satisfactorily to < or = 4 mm . The presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, or Prevotella intermedia at baseline was not associated with the outcome of the periodontal therapy . In conclusion, we found that the presence of the 3 periodontopathogen species had little or no value in predicting healing of periodontal pockets.

Biol Chem, 1999 Nov, 380(11), 1251 - 62
Secretory immunoglobulin A: from mucosal protection to vaccine development; Corthesy B et al.; Immune responses taking place in mucosal tissues are typified by secretory immunoglobulin A (S-IgA) molecules, which are assembled from proteins expressed in two cell lineages . The heavy and light chains as well as the J chain are produced in plasma cells, whereas the secretory component (SC) is associated to the immunoglobulin complex during transcytosis across the epithelial layer . S-IgA antibodies represent the predominant immunoglobulin class in external secretions, and the best defined entity providing specific immune protection for mucosal surfaces by blocking attachment of bacteria and viruses . S-IgA constitutes greater than 80% of all antibodies produced in mucosa-associated lymphoid tissues in humans . The existence of a common mucosal immune system permits immunization on one mucosal surface to induce secretion of antigen-specific S-IgA at distant sites . In addition, S-IgA antibodies not only function in external secretions, but also exert their antimicrobial properties within the epithelial cell during transport across the epithelium . Passive mucosal delivery of monoclonal IgA molecules neutralizes pathogens responsible for gastrointestinal and respiratory infections . Mucosal and systemic immunity can be achieved by orally administered recombinant S-IgA molecules carrying a protective bacterial epitope within the SC polypeptide primary sequence.

Leuk Lymphoma, 1999 Dec, 36(1-2), 33 - 43
Cost analysis of autologous peripheral stem cell transplantation versus autologous bone marrow transplantation for patients with non Hodgkin's lymphoma and acute lymphoblastic leukaemia; Jerjis S et al.; We evaluated the costs of unpurged autologous stem cell transplantation in a non-randomised study of 54 consecutive patients with lymphoproliferative malignancies who have been transplanted at the Nijmegen University Hospital between July 1992 and March 1998 . Thirty-five patients were transplanted with autologous peripheral stem cells (APSCT): 30 had non Hodgkin's lymphoma (NHL) and 5 acute lymphoblastic leukaemia (ALL) . Nineteen patients were transplanted with autologous bone marrow stem cells (ABMT): 17 had NHL and 2 ALL . The number of progenitor cells (CFU-GM, BFU-E) and nucleated cells was significantly higher in peripheral blood transplants . The duration of cytopenia was shorter after APSCT . The leucocyte recovery to 0.5 x 10(9)/L was 13 days for recipients of peripheral stem cells compared to 20 days for bone marrow recipients (P <0.001) . The platelet recoveries to 20 x 10(9)/L were 13 and 29 days, respectively (P = 0.001) . This resulted in significantly shorter admission duration 24 days after APSCT versus 30 days (P = 0.003) after ABMT . Furthermore, a statistically significant difference between both groups was observed for antimicrobial costs (mean: fl 2,939 vs fl 4,888; P = 0.008), platelet transfusions (median: 3 vs 7 units; P = 0.01) and erythrocyte transfusions (median: 6 vs 10 units; P = 0.03) . The mean overall costs were lower in patients transplanted with stem cells from peripheral blood: fl 34,178 versus fl 43,469 (P = 0.007) . This study suggests that the APSCT results in significant cost savings due to shorter hospital stay and less costs of supportive care, despite higher mobilisation costs . The costs of blood transfusions and antimicrobials for patients with ALL were significantly higher when compared to patients with NHL.

J Thorac Cardiovasc Surg, 2000 Jan, 119(1), 108 - 14
Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting; Trick WE et al.; OBJECTIVE: Our objective was to identify risk factors for deep sternal site infection after coronary artery bypass grafting at a community hospital . METHODS: We compared the prevalence of deep sternal site infection among patients having coronary artery bypass grafting during the study (January 1995-March 1998) and pre-study (January 1992-December 1994) periods . We compared any patient having a deep sternal site infection after coronary artery bypass graft surgery during the study period (case-patients) with randomly selected patients who had coronary artery bypass graft surgery but no deep sternal site infection during the same period (control-patients) . RESULTS: Deep sternal site infections were significantly more common during the study than during the pre-study period (30/1796 {1.7%} vs 9/1232 {0.7%}; P =.04) . Among 30 case-patients, 29 (97%) returned to the operating room for sternal debridement or rewiring, and 2 (7%) died . In multivariable analyses, cefuroxime receipt 2 hours or more before incision (odds ratio = 5.0), diabetes mellitus with a preoperative blood glucose level of 200 mg/dL or more (odds ratio = 10.2), and staple use for skin closure (odds ratio = 4.0) were independent risk factors for deep sternal site infection . Staple use was a risk factor only for patients with a normal body mass index . CONCLUSIONS: Appropriate timing of antimicrobial prophylaxis, control of preoperative blood glucose levels, and avoidance of staple use in patients with a normal body mass index should prevent deep sternal site infection after coronary artery bypass graft operations.

J Burn Care Rehabil, 1999 Nov-Dec, 20(6), 501 - 4
Antimicrobial mixtures used to store harvested skin: antimicrobial activities tested at refrigerator (4 degrees C) temperatures; Holder IA et al.; Tissue culture media used by skin and tissue banks to store tissue were tested, with and without antimicrobial mixtures, for their ability to inhibit the growth of bacteria during incubation at refrigerator temperatures . Reductions in bacterial load were found after incubation at 4 degrees C in both the basal tissue culture media with and without the addition of antimicrobial mixtures . The presence of antimicrobials enhanced the degree and rapidity of reduction . Variations occurred among the different formulations, with or without added antimicrobials . No one formulation for either the basal tissue culture medium or antimicrobial mixture was ideal . Methods described in this study can be used to establish optimum basal medium and antimicrobial mixture formulations for general use by skin and tissue banks.

J Burn Care Rehabil, 1999 Nov-Dec, 20(6), 453 - 61
The 1999 clinical research award . Cultured skin substitutes combined with Integra Artificial Skin to replace native skin autograft and allograft for the closure of excised full-thickness burns; Boyce ST et al.; Prompt and permanent closure of excised full-thickness burns remains a critical factor in a patient's recovery from massive burn injuries . Hypothetically, Integra Artificial Skin (Integra) may replace the need for allografts for immediate wound coverage, and cultured skin substitutes (CSS) that contain stratified epithelium may replace the need for autografts for definitive wound closure . To test this hypothesis, 3 patients with full-thickness burns of greater than 60% of their total body surface areas had their eschar excised within 14 days of admission . Integra was applied, and a skin biopsy was collected from each patient for the preparation of CSS . At 3 weeks or more after the application of the Integra and the collection of skin biopsies, the outer silastic cover of the Integra was removed and CSS were grafted . The CSS were irrigated with nutrients and antimicrobials for 6 days and then dressed with antimicrobial ointment and cotton gauze . Treated wounds were traced on days 14 and 28 after the grafting of CSS for determination of engraftment and wound closure, respectively . Cost analysis was not performed . Engraftment on postoperative day (POD) 14 was 98%+/-1% (mean +/- standard error of the mean), the ratio of closed:donor areas on POD 28 was 52.3+/-5.2, and no treated sites required regrafting . The histology of the closed wounds showed stable epithelium that covered a layer of newly formed fibrovascular tissue above the reticulated structure of the degrading Integra . The clinical outcomes of the closed wounds after POD 28 demonstrated smooth, pliable, and hypopigmented skin . Two patients who had received CSS grafts over Integra on their backs were positioned supine on air beds from POD 8 or POD 9 with minimal graft loss because of mechanical loading . One patient with a full-thickness burn of 88% of the total body surface area was covered definitively at 55 days postburn . These results demonstrate that the combination of CSS and Integra can accomplish functionally stable and cosmetically acceptable wound closure in patients with extensive full-thickness burns . This combination of alternatives to the conventional grafting of split-thickness skin permits the substitution of cadaveric allograft with Integra and the substitution of donor autograft with CSS . This approach to the closure of excised full-thickness burns is expected to reduce greatly the time to definitive closure of burn wounds and to reduce the morbidity associated with the harvesting of donor sites for split-thickness skin autografts.

Am J Health Syst Pharm, 1999 Dec 15, 56 Suppl 5, S17 - 20
Treatment of HIV-related neutropenia; Wong RJ; Several studies documenting the association of bacteremia and severity of neutropenia in HIV-infected patients, as well as studies using the colony stimulating factors filgrastim or sargramostim to prevent and treat neutropenia in this patient population, are summarized . Three studies are described in which low absolute neutrophil count was associated with increased incidence of bacterial infections in patients with HIV infection . Two hematopoietic growth factors called colony stimulating factors (filgrastim and sargramostim) are available in the United States, but neither is approved by FDA for the treatment or prevention of neutropenia in HIV-infected patients . Studies have shown both filgrastim and sargramostim to be effective in treating neutropenia in HIV-infected patients without increasing the viral load . In one study, filgrastim use on a daily or intermittent basis was associated with reduction in severe neutropenia or death; in addition, filgrastim-treated patients had fewer bacterial infections, fewer hospital days (both total number of days and days associated only with bacterial infections), and a reduced need for i.v . antimicrobials compared with HIV-infected controls . In another study, neutropenia caused by zidovudine was successfully treated with sargramostim . Both filgrastim and sargramostim show promise in treating and preventing neutropenia in HIV-infected patients . More research is needed to determine the patient population who can best benefit from therapy with these agents and to determine the relative advantages and disadvantages of filgrastim and sargramostim.

Bull World Health Organ, 1999, 77(11), 936 - 45
A clinical training unit for diarrhoea and acute respiratory infections: an intervention for primary health care physicians in Mexico; Bojalil R et al.; In Tlaxcala State, Mexico, we determined that 80% of children who died from diarrhoea or acute respiratory infections (ARI) received medical care before death; in more than 70% of the cases this care was provided by a private physician . Several strategies have been developed to improve physicians' primary health care practices but private practitioners have only rarely been included . The objective of the present study was to evaluate the impact of in-service training on the case management of diarrhoea and ARI among under-5-year-olds provided by private and public primary physicians . The training consisted of a five-day course of in-service practice during which physicians diagnosed and treated sick children attending a centre and conducted clinical discussions of cases under guidance . Each training course was limited to six physicians . Clinical performance was evaluated by observation before and after the courses . The evaluation of diarrhoea case management covered assessment of dehydration, hydration therapy, prescription of antimicrobial and other drugs, advice on diet, and counselling for mothers; that of ARI case management covered diagnosis, decisions on antimicrobial therapy, use of symptomatic drugs, and counselling for mothers . In general the performance of public physicians both before and after the intervention was better than that of private doctors . Most aspects of the case management of children with diarrhoea improved among both groups of physicians after the course; the proportion of private physicians who had five or six correct elements out of six increased from 14% to 37%: for public physicians the corresponding increase was from 53% to 73% . In ARI case management, decisions taken on antimicrobial therapy and symptomatic drug use improved in both groups; the proportion of private physicians with at least three correct elements out of four increased from 13% to 42%, while among public doctors the corresponding increase was from 43% to 78% . Hands-on training courses thus seemed to be effective in improving the practice of physicians in both the private and public sectorsPIP: This study evaluated the impact of an in-service training course for physicians on diarrhea and acute respiratory infection (ARI) management in children under age 5 in Tlaxcala, Mexico, between January 1993 and April 1994 . The training consisted of a 5-day course of in-service practice, during which physicians diagnosed and treated sick children attending a center and conducted clinical discussions of cases under guidance . Each training course was limited to 6 physicians . Clinical performance was evaluated by observation before and after the courses . The evaluation of diarrhea case management covered assessment of dehydration, hydration therapy, prescription of antimicrobial and other drugs, advice on diet, and counseling of mothers . The evaluation of ARI case management, on the other hand, covered diagnosis, decisions on antimicrobial therapy, use of symptomatic drugs, and counseling of mothers . The study revealed that the performance of public physicians before and after the intervention was better compared to those of private doctors . Most aspects of case management of children with diarrhea improved among both groups of physicians after the course . The proportion of private doctors who had 5 or 6 correct elements out of 6 increased from 14% to 37%, while for public doctors the corresponding increase was from 53% to 73% . As for the ARI case management, decisions taken on antimicrobial therapy and symptomatic drug use improved in both groups . The proportion of private physicians with at least 3 correct elements out of 4 increased from 13% to 42%, while among the public doctors, the corresponding increase was from 43% to 78% .

Peptides, 1999 Nov, 20(11), 1265 - 73
Antimicrobial activity of polycationic peptides; Giacometti A et al.; The in vitro activity of six polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, nisin, and ranalexin, were evaluated against several clinical isolates of gram-positive and gram-negative aerobic bacteria, yeasts, Pneumocystis carinii and Cryptosporidium parvum, by using microbroth dilution methods . The peptides exhibited different antibacterial activities and rapid time-dependent killing . The gram-negative organisms were more susceptible to buforin II and cecropin P1, whereas buforin II and ranalexin were the most active compounds against the gram-positive strains . Similarly, ranalexin showed the highest activity against Candida spp., whereas magainin II exerted the highest anticryptococcal activity . Finally, the peptides showed high anti-Pneumocystis activity, whereas no compound had strong inhibitory effect on C . parvum.

Clin Orthop, 1999 Dec, (369), 124 - 38
The use of prophylactic antimicrobial agents during and after hip arthroplasty; Hanssen AD et al.; An intravenous antibiotic, administered just before skin incision, effectively reduces the prevalence of deep wound infection . The optimal antimicrobial agent has not been determined definitively; however, a short duration of prophylaxis is recommended . Institutional compliance strategies are cost-effective and improve the timing of antibiotic administration . Also, published antimicrobial restriction recommendations are warranted because of the concern of emerging antibiotic-resistant bacteria . Specifically, restriction of vancomycin in orthopaedic surgery should be targeted critically . Supplemental antibiotic administration includes additional intra-operative antibiotic dosing, use of antibiotic-irrigant solutions, and admixture of antibiotics into acrylic bone cement or bone graft . There are no established standards or clinical guidelines for these supplemental antibiotic applications . Post-operatively, antimicrobial agents frequently are overused for various clinical scenarios and this pattern of antibiotic usage is potentially detrimental . A prophylaxis strategy for prevention of early and late hematogenous infection requires consideration of host risk factors, wound environment variables, and sources of potential bacteremia . This strategy should include deliberation of the cost-effectiveness, efficacy, and complications associated with routine use of antibiotics . Advisory statements for elective procedures, which potentially may cause bacteremia, are being developed and additional research is required for this area of antimicrobial agent prophylaxis.

J Infect Dis, 2000 Jan, 181(1), 252 - 60
Heterogeneous virulence of enteroaggregative Escherichia coli strains isolated from children in Southwest Nigeria; Okeke IN et al.; Enteroaggregative Escherichia coli (EAEC) has been implicated in acute and persistent diarrhea, and most strains harbor a member of a partially-conserved plasmid family (called pAA) . We studied EAEC isolated from Nigerian children aged <5 years to elucidate the roles of plasmid and chromosomal EAEC loci . We tested a total of 131 EAEC strains isolated from acute diarrhea case patients and control subjects for hybridization with 8 pAA plasmid-derived and 2 chromosomal gene probes, for several in vitro phenotypes and for resistance to antimicrobial agents . Using by multiple logistic regression, we found genes encoding the AAF/II fimbriae to be strongly associated with diarrhea in this population . EAEC strains appear to be of heterogeneous virulence, and data suggest that AAF/II may be a marker for pathogenic strains.

Res Vet Sci, 1999 Dec, 67(3), 301 - 3
Serovar, pathogenicity and antimicrobial susceptibility of erysipelothrix rhusiopathiae isolates from farmed wild boars (Sus scrofa) affected with septicemic erysipelas in Japan; Yamamoto K et al.; Six strains of Erysipelothrix rhusiopathiae were isolated from farmed wild boars with acute septicemic erysipelas during the period from 1983 to 1998 in Japan . All isolates belonged to serovar 1a or 2 (predominant serovars in swine) . The 50 per cent lethal dose values of those isolates ranged from 10(1.3)to 10(6.2)colony forming units in mice . In swine, all isolates were virulent, capable of inducing localized or generalized urticarial lesions after intradermal inoculation . All of the isolates were resistant to oxytetracycline and/or dihydrostreptomycin . These observations suggest that E . rhusiopathiae strains isolated from wild boars may have aetiological significance in swine erysipelas .

Med Res Rev, 2000 Jan, 20(1), 58 - 101
Soft drug design: general principles and recent applications; Bodor N et al.; Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process . Soft drugs are new therapeutic agents that undergo predictable metabolism to inactive metabolites after exerting their therapeutic effect . Hence, they are obtained by building into the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified . In an attempt to systematize and summarize the related work done in a number of laboratories, including ours, the present review presents an overview of the general soft drug design principles and provides a variety of specific examples to illustrate the concepts . A number of already marketed drugs, such as esmolol, remifentanil, or loteprednol etabonate, resulted from the successful application of such design principles . Many other promising drug candidates are currently under investigation in a variety of fields including possible soft antimicrobials, anticholinergics, corticosteroids, beta-blockers, analgetics, ACE inhibitors, antiarrhythmics, and others . Whenever possible, pharmacokinetic and pharmacodynamic properties are briefly summarized and compared to those of other compounds used in the same field .

What Is Water Purification?, What Is Molecular Biology?, What Is Yeast?, What Is Botulism?, What Is Biotechnology?, i, Microorganisms, c, Microbe, r, Microbes, i, Microorganism, i, Microbiology, c, Escherichia coli, r, P. fluorescens, n, S. cerevisiae, o, Prokaryotes, i, Antibiotic treatment, r, Wastewater, r, Microorganism, e, Microbiological, i, Microorganisms, o, Multidrug resistant, a, Anaerobes, n, Microorganism, i, Prokaryotes, e, Streptococcal, o, Clostridia, e, Bacillus subtilis, c, Salmonella typhimurium, o, Microorganisms, s, Bacteriophages, a, Lactobacillus, e, Escherichia coli

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

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

Last modified: May 25, 2005