Bactericidal

J Pediatr Surg, 1998 May, 33(5), 756 - 8
Junctional epidermolysis bullosa: diagnosis and management of a patient with the Herlitz variant; Goldstein AM et al.; A case of Herlitz-type epidermolysis bullosa (EB) is reported . The baby was born after a normal, full-term pregnancy with blisters on his extremities . Over the next several months, progressive skin sloughing involving 95% of his body surface area developed, including gastrointestinal, laryngeal, tracheobronchial, and corneal involvement . The diagnosis of junctional EB, Herlitz type, was made using clinical, electron microscopic, and immunohistochemical criteria . Despite meticulous wound care, aggressive nutritional support, and continuous antimicrobial therapy, the baby died at 9 months of age . This report discusses the presentation, complications, and management of this unusual and tragic disease.

Kidney Int, 1998 Jun, 53(6), 1792 - 4
Treatment of infected tunneled venous access hemodialysis catheters with guidewire exchange; Robinson D et al.; Cuffed venous access catheters have become commonplace for hemodialysis access . The major complications of these catheters are catheter thrombosis, catheter fibrin sheathing and infection . When catheter associated bacteremia occurs treatment with antimicrobial therapy alone has been unsuccessful in providing acceptable cure rates . Failed antimicrobial therapy exposes the patient to the risks of prolonged bacteremia, while the alternative, catheter replacement at a new site can lead to central venous stenosis and compromise future long-term upper extremity access . Catheter guidewire exchange when the tunnel tract is clinically not infected theoretically allows the preservation of future access sites and yields a higher treatment success rate while avoiding temporary non-cuffed access placement . We report a series of 23 cases of hemodialysis patients with tunneled cuffed catheters and bacteremia related to the catheter who were treated with the exchange of a new catheter over a guidewire combined with three weeks of systemic antibiotics . Patients eligible for the study required no evidence of tunnel tract infection and defervescence within 48 hours of antimicrobial therapy . Technique failure was defined as repeat infection from any organism within 90 days of catheter exchange . Four patients (18%) redeveloped bacteremia within 90 days of the exchange . The bacteremias developed at 4, 19, 63 and at 74 days days after the exchange . Guidewire exchange in combination with intravenous antibiotics in cases of catheter related bacteremia has an acceptable rate of treatment success and is a viable treatment option in a carefully selected patient population.

Biochim Biophys Acta, 1998 Apr 24, 1402(3), 250 - 60
A chemically modified tetracycline inhibits streptozotocin-induced diabetic depression of skin collagen synthesis and steady-state type I procollagen mRNA; Craig RG et al.; Wasting of connective tissues including skin, bone, and cartilage have been closely associated with elevated matrix metalloproteinase (MMP) activity and depressed collagen content in the streptozotocin (STZ)-induced diabetic rat, while tetracyclines have been reported to normalize total body weight, skin hydroxyproline and collagen content in this model, in part through inhibition of MMPs . In the present study, we report the effect of CMT-1, a chemically modified tetracycline that lacks antimicrobial properties but retains divalent cation binding and MMP inhibitory activity, on diabetic skin collagen synthesis and steady-state levels of procollagen alpha 1(I) mRNA . Male, 4-month old Sprague-Dawley rats received a single injection of 75 mg/kg STZ or citrate vehicle alone and diabetic status was confirmed by positive glucosuria . Some diabetic animals received 10 mg/day of CMT-1 by oral gavage and, 28 days after STZ treatment, body weight, blood glucose values and the in vivo rates of skin collagen production were measured using the pool-expansion technique . Steady-state levels of procollagen alpha 1(I) mRNA were analyzed 21 days after STZ treatment by hybridization of total RNA with a 32P labelled cDNA to rat type I procollagen alpha 1(I) mRNA in a dot-blot assay . STZ treatment was found to significantly depress body weight, skin collagen hydroxyproline content, the in vivo rate of collagen production, and hybridizable levels of type I procollagen alpha 1(I) mRNA . CMT-1 administered daily to STZ-treated rats inhibited the diabetic depression of these parameters but had little or no effect on non-diabetic controls or on STZ-induced hyperglycemia . Thus, in addition to the inhibition of MMP mediated extracellular collagen degradation, these results suggest CMT-1 also acts to inhibit diabetic connective tissue breakdown in STZ-induced diabetes by increasing both steady-state levels of type I procollagen mRNA and collagen synthesis through mechanism(s) that are independent of the antibacterial properties of tetracyclines.

Rheum Dis Clin North Am, 1998 May, 24(2), 305 - 22
Gonococcal arthritis; Cucurull E et al.; Disseminated gonococcal infection is the most common systemic complication of acute gonorrhea and occurs in 0.5% to 3.0% of patients with untreated mucosal infection . It is also the most common cause of septic arthritis in patients less than 30 years of age . Fortunately, the incidence of gonorrhea is decreasing dramatically in the United States and Western Europe, although it is still high in developing countries . Increasing resistance to antibiotics requires continuous surveillance of antimicrobial susceptibilities to determine the efficacy of current therapeutic measures.

Rheum Dis Clin North Am, 1998 May, 24(2), 287 - 304
Septic arthritis in children; Shetty AK et al.; Because of its seriousness, septic arthritis should be considered early in the differential diagnosis of any child presenting with joint inflammation . Physicians who care for children should be aware of the early signs and symptoms of septic arthritis and be aggressive about establishing the diagnosis so that treatment is not delayed . Early orthopedic consultation and a low threshold for performing arthrocentesis are prudent . Prolonged and appropriate antimicrobial therapy is warranted to achieve optimal results.

J Biol Chem, 1998 Apr 24, 273(17), 10463 - 9
In vivo regulation of the IkappaB homologue cactus during the immune response of Drosophila; Nicolas E et al.; The dorsoventral regulatory gene pathway (spatzle/Toll/cactus) controls the expression of several antimicrobial genes during the immune response of Drosophila . This regulatory cascade shows striking similarities with the cytokine-induced activation cascade of NF-kappaB during the inflammatory response in mammals . Here, we have studied the regulation of the IkappaB homologue Cactus in the fat body during the immune response . We observe that the cactus gene is up-regulated in response to immune challenge . Interestingly, the expression of the cactus gene is controlled by the spatzle/Toll/cactus gene pathway, indicating that the cactus gene is autoregulated . We also show that two Cactus isoforms are expressed in the cytoplasm of fat body cells and that they are rapidly degraded and resynthesized after immune challenge . This degradation is also dependent on the Toll signaling pathway . Altogether, our results underline the striking similarities between the regulation of IkappaB and cactus during the immune response.

Rheumatol Int, 1998, 17(5), 175 - 80
Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis; Nordstrom D et al.; Tetracyclines exert, independently of their antimicrobial activity, anti-collagenolytic effects by inhibiting activities of human interstitial collagenases and by preventing the oxidative activation of latent pro-collagenases . We tested the clinical response to a 3-month doxycycline in concert with collagenase activity in 12 rheumatoid arthritis (RA) patients . Patients received 150 mg/day of doxycycline for 3 months . Clinical assessments at zero, six and 12 weeks comprised classification of the functional class, joint score index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS) of pain, pain disability index, comprehensible psychopathological rating scale (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and Western blots . Significant reductions were seen in joint score index (P < 0.01), pain VAS (P < 0.05) and some CPRS parameters . Furthermore, collagenase activities measured from saliva by quantitative SDS-PAGE electrophoresis were significantly reduced during the 12-week intervention (P < 0.01) . Western blots demonstrated intact 75-80 kDa enzyme protein (classic neutrophil collagenase), but also a newly discovered mesenchymal, less glycosylated 40-55 kDa MMP-8 subtype of fibroblast/chondrocytic origin . These results indicate that the documented favourable clinical response may in part be due to in vivo inhibition of classic neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline . This anti-collagenolytic doxycycline effects is mediated through inhibition of the enzyme activity and not through degradation of the enzyme, which may have contributed to the reportedly reduced tissue destruction, as has been seen in clinical studies concerning RA as well as reactive arthritis.

J Chemother, 1998 Apr, 10(2), 91 - 6
Immunopharmacology of oral betalactams; Periti P; Among the oral beta-lactam antibiotics only cefaclor has demonstrated a consistent in vitro and in vivo immunopharmacological effect which favors phagocytic chemotaxis and antimicrobial potential by inducing a T-helper 1 or pro-inflammatory response . Together with cefpimizole, cefaclor significantly reduces the minimum bactericidal concentration (MBC) against some bacterial species when cultured together with a suspension of polymorphonuclear leukocytes, as opposed to some other oral beta-lactams, co-amoxiclav and cefixime, which do not show this effect . The pro-inflammatory component of cefaclor's activity explains the clinical success of this antibiotic in a high percentage of cases, even when laboratory tests indicate in vitro resistance by the pathogen.

J Chemother, 1998 Apr, 10(2), 83 - 90
Selecting antibacterial agents for the control of surgical infection: mini-review; Periti P et al.; An analysis of the recent literature on the control of surgical infections confirms the role of antimicrobial agents which guarantee valid perioperative antisepsis in both clean and clean-contaminated surgery . Current chemotherapy is able to check serious postoperative infectious complications by reducing the risk of septic shock with use of a glycopeptide-aminoglycoside-betalactam combination together with anti-inflammatory drugs.

Exp Parasitol, 1998 May, 89(1), 103 - 12
Plasmodium gallinaceum: differential killing of some mosquito stages of the parasite by insect defensin; Shahabuddin M et al.; We examined several insect antimicrobial peptides to study their effect on Plasmodium gallinaceum zygotes, ookinetes, oocysts, and sporozoites . Only two insect defensins-Aeschna cyanea (dragon fly) and Phormia terranovae (flesh fly)-had a profound toxic effect on the oocysts in Aedes aegypti and on isolated sporozoites . The defensins affected the oocysts in a time-dependent manner . Injecting the peptide into the hemolymph 1 or 2 days after an infectious blood meal had no significant effect on prevalence of infection or relative oocyst density per mosquito . When injected 3 days after parasite ingestion, the relative oocyst density was significantly reduced . Injection on day 4 or later damaged the developing oocysts, although the oocysts density per mosquito was not significantly different when examined on day 8 . The oocysts were swollen or had extensive internal vacuolization . The peptides had no detectable effect on the early stages of the parasite: the zygotes and ookinetes tested in vitro . Both the defensins were highly toxic to isolated sporozoites in vitro as indicated by disruption of the membrane permeability barrier, a change in morphology, and loss of motility . In contrast to the toxicity of cecropin and magainin for mosquitoes, defensin, at concentrations that kill parasites, is not toxic to mosquitoes, suggesting that defensin should be studied further as a potential molecule to block sporogonic development of Plasmodium.

Poult Sci, 1998 May, 77(5), 765 - 9
Sodium lactate affects sensory and objective characteristics of tray-packed broiler chicken breast meat; Williams SK et al.; The objective of this study was to determine the antimicrobial properties of sodium lactate solutions adjusted to various pH values . The effectiveness of sodium lactate increases with increased concentrations; however, there are off-flavor development problems associated with increasing concentrations of sodium lactate above 2.0% . This study evaluated the effects of 2% sodium lactate treatments, adjusted to various pH values, on sensory characteristics, instrumental texture, and microbial populations of tray-packed broiler breast meat . Breast meat was treated with either tap water (pH 7.85) or 2% sodium lactate solutions (pH 7.30, 5.50, 5.00, 4.50, and 4.00) and stored at 2 +/- 1 C for 12 d . Approximately 15% of the panelists reported acidic aftertastes in samples treated with pH 5.00 sodium lactate solutions, and 10% of the panelists reported slight sodium or metallic off-flavor in all samples treated with sodium lactate . Instrumental texture measurements were similar (P > 0.05) for all treatments . Sodium lactate (pH 7.30 and 5.50) enhanced (P < 0.05) cooking yields and retarded the growth of spoilage bacteria (pH 5.50 and 5.00) . Due to the development of severe discoloration and intense acidic off-odors and -flavors, testing was not conducted on samples treated with pH 4.50 and 4.00 sodium lactate solutions.

Food Addit Contam, 1998 Feb-Mar, 15(2), 162 - 70
Contamination of animal feedingstuffs with undeclared antimicrobial additives; Lynas L et al.; A study was carried out on 397 feedingstuffs and 11 premixes on which 161 (39.5%) were declared free of medication and 247 (60.5%) were medicated . These were subjected to analysis for the presence of antibiotics . Of the 247 medicated feeds 87 (35.2%) contained undeclared antimicrobials of which 59 (23.9%) were at a concentration sufficient to allow quantification by HPLC . Of the 161 unmedicated feeds 71 (44.1%) were shown to contain detectable antimicrobials of which 42 (26.1%) contained concentrations which could be quantified by HPLC . The most frequently identified contaminating antimicrobials were chlortetracycline (CTC) (15.2%), sulphonamides (6.9%), penicillin (3.4%) and ionophores (3.4%) . Four samples (ionophores--3, sulphadimidine--1) contained therapeutic concentrations and one sample a supra-therapeutic concentration (monensin) . The remainder were sub-therapeutic . All the contaminating concentrations of sulphadimidine detected were sufficient to cause violative tissue residues if fed to animals immediately prior to slaughter.

Infect Immun, 1998 Jun, 66(6), 2426 - 33
Differential gene expression in response to adjunctive recombinant human interleukin-2 immunotherapy in multidrug-resistant tuberculosis patients; Johnson BJ et al.; Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with multidrug chemotherapy to patients with multidrug-resistant tuberculosis (MDR TB) induces measurable changes in in vitro immune response parameters which are associated with changes in the clinical and bacteriologic status of the patients . To determine the molecular basis of these changes, we have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and differential display technology . During rhuIL-2 treatment of MDR TB patients, decreased levels of gamma interferon (IFN-gamma) mRNA in peripheral blood mononuclear cells (PBMC) relative to baseline levels were observed . However, at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD), the expression of cellular IFN-gamma and IL-2 mRNAs was increased during rhuIL-2 therapy . Levels of other cytokine mRNAs were not significantly affected by rhuIL-2 administration . Using differential-display RT-PCR, we identified several genes expressed at the DTH skin test site which were up- or down-regulated during rhuIL-2 treatment . Cytochrome oxidase type I mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as was heterogeneous nuclear ribonuclear protein G mRNA . CD63, clathrin heavy chain, and beta-adaptin mRNAs, all of which encode proteins associated with the endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL-2 administration . The differential effects of IL-2 were confirmed in vitro by using PBMC obtained from PPD-positive individuals stimulated with Mycobacterium tuberculosis and IL-2 . The differential expression of genes may provide a surrogate marker for leukocyte activation at a mycobacterial antigen-specific response site and for the development of an enhanced antimicrobial response which may result in improved outcomes in MDR TB patients.

J Rheumatol, 1998 May, 25(5), 975 - 82
Functional sites of chemically modified tetracyclines: inhibition of the oxidative activation of human neutrophil and chicken osteoclast pro-matrix metalloproteinases; Sorsa T et al.; OBJECTIVE: We studied the relative ability of 6 different chemically modified non-antimicrobial analogs of tetracycline (CMT) to inhibit human and chicken matrix metalloproteinases (MMP) in vitro . The ability of tetracycline and its analogs to inhibit MMP appears to depend on the Ca++/Zn++ binding site at C11 (carbonyl oxygen) and C12 (OH group) of the molecule, which is lacking in CMT-5, the pyrazole derivative of tetracycline . This significant property of CMT-5 was used to differentiate between the effects of CMT on already active MMP versus the oxidative activation of latent MMP (pro-MMP) . METHODS: Cultured chicken osteoclast conditioned medium and purified human neutrophil progelatinase (MMP-9) and pro-collagenase (MMP-8) were assayed for proteinase activities using gelatin and collagen, respectively . The pro-MMP were activated either by preincubation with 1 mM aminophenylmercuric acetate (APMA) or 100 microM sodium hypochlorite (NaOCI) . CMT were added either to the preincubation mixtures together with NaOCl or after activation of pro-MMP with NaOCl . RESULTS: All CMT tested, except CMT-5, inhibited APMA or NaOCl activated pro-MMP . However, CMT-5 (like the other CMT), inhibited the oxidative activation of pro-MMP by NaOCl when added together by scavenging the reactive oxygen species . The degradation of type-I collagen by chicken osteoclast conditioned medium was probably due to MMP-2 and/or MMP-13 . CONCLUSION: Oxidative activation of pro-MMP may be crucial during soft tissue/bone destruction in the inflammatory diseases, including the arthritides . Our results indicate that the Ca++/Zn++ binding site of CMT is not essential for inhibition of the oxidative activation of pro-MMP.

South Med J, 1998 May, 91(5), 464 - 6
Chromobacterium violaceum infection; Midani S et al.; Chromobacterium violaceum infection is confined to the tropical and subtropical areas, with almost all reported cases occurring in the Southeast . The most common feature of this infection is sepsis, followed by cutaneous involvement and liver abscesses . Treatment consists of surgical drainage of purulent collections and appropriate antimicrobial therapy, such as chloramphenicol, gentamicin, imipenem, trimethoprim-sulfamethoxazole, or ciprofloxacin . Although C violaceum infection is rare, it is potentially fatal and remains an important entity for clinicians to suspect and treat appropriately.

J Antimicrob Chemother, 1998 Apr, 41(4), 467 - 80
Clinical trials of antibacterial agents: a practical guide to design and analysis . Statisticians in the Pharmaceutical Industry Working Party; Smith C et al.; Guidelines on the conduct of clinical trials of antibacterial agents produced by the US Food and Drug Administration, the British Society for Antimicrobial Chemotherapy, the Infectious Diseases Society of America and a European Working Party have been reviewed . Although very informative, these guidelines provide limited practical guidance on the design and statistical aspects of phase III studies of antimicrobial agents . This paper describes the differences between antibacterial trials and clinical studies in other therapeutic areas with regard to subjective endpoints, dual clinical and bacteriological endpoints, frequent protocol violations and difficulty of using placebo controls . The importance of a detailed protocol and planned analysis strategy is emphasized . The choice of comparator agents, practical issues with the blinding of trial materials and the documentation of patients excluded from study entry are discussed . The use of different patient groups and different endpoints in analyses are described . The principles of equivalence and their application to trials of antibacterial agents are discussed, together with an approach to calculating sample size . A variety of statistical analyses of results are compared for different situations indicating some of the problems that can arise . Different methods of presentation of study data are included with emphasis on regulatory submissions rather than scientific publications . Some graphical presentations are recommended and issues regarding data across different studies are discussed.

Adv Exp Med Biol, 1998, 434, 213 - 35
Maillard reaction and food processing . Application aspects; Chuyen NV; The Maillard reaction occurs widely in food and biological systems . This contribution reviews the relation between the Maillard reaction and food processing, particularly its contribution to flavor formation, antioxidative effects, desmutagenic activity and the improvement of protein functional properties . Proteins modified by glucose, and melanoidins are important components of foodstuffs while the reactions of amino acids or peptides with glucose or dicarbonyl compounds produce various kinds of flavor components . Melanoidins and Amadori rearrangement products play an important role in providing antioxidative effects, both in vitro and in vivo . Melanoidins also exhibit desmutagenic activity against carcinogenic compounds . Protein-polysaccharide conjugates, prepared by Maillard reaction at mild conditions, increase the emulsifying activity, as well as antioxidative and antimicrobial effects of the original proteins.

J Clin Pharmacol, 1998 Jan, 38(1), 90 - 3
Levofloxacin does not alter cyclosporine disposition; Doose DR et al.; Certain fluoroquinolones have been shown to elevate the serum concentrations of the immunosuppressant cyclosporine . It is thus important to investigate the potential interaction between levofloxacin, a new fluoroquinolone antimicrobial agent, and the pharmacokinetics of cyclosporine . Twelve healthy subjects (6 men, 6 women) were enrolled in and completed a placebo-controlled, randomized, double-blind, two-phase crossover study . Subjects were given a single oral 10-mg/kg dose of cyclosporine solution during multiple-dose twice-daily oral treatment with placebo or 500 mg of levofloxacin . Blood cyclosporine concentrations were measured for 48 hours after each cyclosporine dose for pharmacokinetic evaluation . Cyclosporine pharmacokinetic parameters were comparable and not significantly different in the absence and presence of levofloxacin . Results of this study suggest that a clinically important pharmacokinetic interaction between levofloxacin and cyclosporine is unlikely to occur during concurrent therapy.

Dent Clin North Am, 1998 Apr, 42(2), 263 - 83
Controlled local delivery of antimicrobials in the treatment of periodontitis; Killoy WJ et al.; Five local delivery systems with five different antimicrobial agents have been discussed . All are capable of delivering high concentrations of their antimicrobial to the site of the periodontal infection . Although only one system, tetracycline fiber, is available in United States, two other systems, chlorhexidine chip and doxycycline polymer, may be available in the near future . Two other systems, metronidazole gel and minocycline ointment, are available in other countries . Data from pertinent studies were presented as were techniques for using the various systems . Indications for the use of the products were also discussed . In selecting the appropriate delivery system, the clinician has to weigh the efficacy of the products, ease of use, availability, and cost . Although local delivery systems do not replace existing periodontal therapies, they do have a place in the treatment of periodontitis and offer the dentist additional methods to aid in the control of periodontal diseases.

Dent Clin North Am, 1998 Apr, 42(2), 245 - 62
Pharmacologic management of periodontal diseases using systemically administered agents; Mariotti A et al.; Since the establishment of bacteria-laden plaque as a causative agent in gingivitis, the search for specific bacteria that induce different types of periodontitis has generated extensive research . In contrast to many other microbial-induced disorders, the specific periodontal pathogen(s) has not been identified to date . Therefore, the search for an effective systemic agent to prevent the loss of attachment through the selective reduction of known periodontal pathogens has remained elusive . It is not surprising then that antibiotics are not used solely to manage periodontal diseases but rather as an adjunct to the mechanical debridement of root surfaces in select periodontal diseases . Further, the sole use of antibiotics in patients with adult periodontitis (or those who exhibit signs of inflammation but are periodontally stable) has shown little benefit and only increases the chance of microbial resistance to antibiotics . Despite these limitations, considerable progress in antibiotic therapy has delivered regimens that enhance the effectiveness of conventional therapy . In contrast to traditional antimicrobial therapy, new treatment modalities have begun to focus on modulating the responses of host cells to bacteria rather than modulating only the bacteria . Current drugs used to regulate host cells inhibit the cyclooxygenase pathway, reduce the activity of metalloproteinases, or inactivate bone resorptive cells (see Table 1) . Although these drugs offer great potential to modulate a variety of mammalian cells, a notable and consequential limitation of these agents is a lack of specificity . Inflammation, bone metabolism, and connective tissue metabolism are two-edged swords; all are necessary for the homeostasis of the tissue, but some or all may also be involved in the pathologic destruction of that same tissue . Hence, drugs that inhibit destruction of the connective tissue in one site of the periodontium also interfere with wound healing at another . As a result of these limitations, the efficacy, safety, and cost-effectiveness of the long-term use of these agents is unknown . Preliminary results of treatment with these drugs are promising, and future generations of host-modulating drugs will provide clinicians with additional agents to help improve the success rate of periodontal treatment for patients . Antibiotics remain an important adjunctive therapy in the treatment of periodontal diseases, and the use of host modulating drugs as supplemental agents in the management of periodontal diseases continues to grow . As more knowledge is gained about the causes of periodontal diseases, new drugs that are potent, effective, site specific, and safe can be delivered at optimal times by simply having the patient take a few tablets . Considering the dramatic progress in the past decade in understanding the cause and pharmacologic management of periodontal diseases, the twenty-first century holds great promise for the development of magic bullets.

Zhonghua Yi Xue Za Zhi, 1997 Feb, 77(2), 91 - 3
{Polymerase chain reaction in the detection of patients infected by Chlamydia trachomatis after treatment}; Wang H et al.; OBJECTIVE: To investigate the value of polymerase chain reaction (PCR) for follow-up patients infected by Chlamydia trachomatis . METHODS: Follow-up specimens were collected from 30 patients . Chlamydia trachomatis positive were detected by PCR and direct fluorescence assay test (DFA) in the 30 patients before therapy . 15 patients were treated with minocycline (100 mg twice daily) for 10 days, and 15 patients were treated with 1.0 g of azithromycine as a single oral dose . RESULTS: After 1-2 weeks of antimicrobial therapy, all patients had negative DFA for Chlamydia trachomatis, but 9 had positive Chlamydia trachomatis DNA as detected by PCR . CONCLUSIONS: The 9 specimens were not confirmed to livae viable organisms of Chlamydia trachomatis . The debris of nonviable Chlamydia trachomatis DNA was excluded from urinogenital tract at about one month.

Croat Med J, 1998 Mar, 39(1), 28 - 32
Recovery of respiratory functional defects after war injuries to the chest; Ilic N et al.; AIM: Assessment of lung function before, during, and after surgical treatment of war injuries to the chest, and comparison of conservative and operative surgical approach . PATIENTS AND METHODS: A retrospective study of 439 patients with war injuries to the chest inflicted during the wars in Croatia and Bosnia and Herzegovina was performed . Patients were classified by injury mechanism and by physiologic scoring on admission, according to the cardiovascular-respiratory elements of the Injury Severity Score (ISS) . "Conservative" surgical treatment with chest tube drainage, appropriate fluid therapy, and antimicrobial and atelectasis prophylaxis was performed in 358 (81.5%) and operations in 81 (18 . 5%) patients . Blood gases were analyzed before, during, and after surgical treatments . Pulmonary function was assessed after the stabilization of patients' clinical condition and 3-6 months after the injury . RESULTS: On admission, blood gas profiles showed slight to moderate hypoxemia with consecutive hypercapnia related to the severity of injuries . Surgical treatment left a minimum degree restrictive disorder of ventilation without an obstructive pattern . Definitive repair of lung function presented with normalization of blood gas data, and significantly improved restrictive pattern (p<0.05) . There was no difference in definitive lung function between conservatively and operatively treated patients . Mortality was 2% . CONCLUSION: The success of surgical resuscitation was related to ISS scoring . Recovery of respiratory function defects after the injury was not significantly related to the mechanism of injury or the patient's condition at arrival . The recovery of lung function was similar in conservatively and operatively treated patients.

Med Care, 1998 May, 36(5), 646 - 60
Influence of the NIH Consensus Conference on Helicobacter pylori on physician prescribing among a Medicaid population; Thamer M et al.; OBJECTIVES: In February 1994, an National Institutes of Health (NIH) Consensus Development Conference panel unequivocally recommended antimicrobial therapy to eradicate Helicobacter pylori in the treatment of peptic ulcer disease . The goal of this study was to determine if these recommendations resulted in a change in physician prescribing among an underserved population . METHODS: Computerized Pennsylvania Medicaid data from January 1993 through February 1996 were used to evaluate prescribing patterns in the year before and 2 years after the NIH conference . An interrupted time series model, based on 12,737 outpatient peptic ulcer disease encounters, assessed the impact of the conference in influencing physician prescribing . RESULTS: The prescription of antimicrobial agents for the treatment of peptic ulcer disease significantly increased across the study period, from 6.5% in January 1993 to 10.2% in February 1996 . Similarly, the prescription rate for the proton pump inhibitor, omeprazole, significantly increased from 9.4% in January 1993 to 25.6% in February 1996 . Neither trend, however, could be attributed to the NIH Consensus Development Conference . Stratification by physician specialty, ulcer type, nonsteroidal anti-inflammatory drug use, and patient demographics did not affect these results . The traditional treatment approach, using H2-receptor antagonists, remained the preferred pharmacotherapy (72% of all prescriptions) . CONCLUSIONS: Two years after the highly publicized NIH conference on the eradication of Helicobacter pylori, antimicrobial agents were not widely prescribed among the Pennsylvania Medicaid population . In treating this underserved population, physicians do not appear to be using recommendations developed by an NIH expert panel based on recent scientific advances.

Boll Chim Farm, 1998 Feb, 137(2), 43 - 7
Synthesis of some new biologically active 2,3-disubstituted quinazolin-4-ones; Abdel-Rahman TM; The facile synthesis of 2-(2'-4-anisoylvinyl)-3-arylquinazolin-4-ones (2a, b) involves the condensation of 2-toluidine or 4-phenylenediamine with the corresponding 2-{2'-(4-anisoylvinyl)}-4H-3,1-benzoxazine-4-one (1) . Reaction of compound 2 with aldehydes, bromine, alcohols, hydrazine hydrate, urea and thiourea are discussed . The former structure of the products have been characterized by elemental analysis and spectral data . Preliminary screening of some selected compounds for antimicrobial activity is reported.

Subcell Biochem, 1998, 29, 321 - 41
Biosynthesis and regulation of coronatine, a non-host-specific phytotoxin produced by Pseudomonas syringae; Bender CL et al.; Many P . syringae pathovars are known to produce low-molecular-weight, diffusible toxins in infected host plants . These phytotoxins reproduce some of the symptoms of the relevant bacterial disease and are effective at very low concentrations . Phytotoxins generally enhance the virulence of the P . syringae pathovar which produces them, but are not required for pathogenesis . Genes encoding phytotoxin production have been identified and cloned from several P . syringae pathovars . With the exception of coronatine, toxin biosynthetic gene clusters are generally chromosomally encoded . In several pathovars, the toxin biosynthetic gene cluster also contains a resistance gene which functions to protect the producing strain from the biocidal effects of the toxin . In the case of phaseolotoxin, a resistance gene (argK) has been utilized to engineer phaseolotoxin-resistant tobacco plants . Although P . syringae phytotoxins can induce very similar effects in plants (chlorosis and necrosis), their biosynthesis and mode of action can be quite different . Knowledge of the biosynthetic pathways to these toxins and the cloning of the structural genes for their biosynthesis has relevance to the development of new bioactive compounds with altered specificity . For example, polyketides constitute a huge family of structurally diverse natural products including antibiotics, chemotherapeutic compounds, and antiparasitics . Most of the research on polyketide synthesis in bacteria has focused on compounds synthesized by Streptomyces or other actinomycetes . It is also important to note that it is now possible to utilize a genetic rather than synthetic approach to biosynthesize novel polyketides with altered biological properties (Hutchinson and Fujii, 1995; Kao et al., 1994; Donadio et al., 1993; Katz and Donadio, 1993) . Most of the reprogramming or engineering of novel polyketides has been done using actinomycete PKSs, but much of this technology could also be applied to polyketides synthesized by Pseudomonas when sufficient sequence information is available . It is important to note that Pseudomonas produces a variety of antimicrobial compounds from the polyketide pathway, including mupirocin (pseudomonic acid) (Feline et al., 1977), pyoluteorin (Cuppels et al., 1986), and 2-4 diacetylphloroglucinol (Phl) (Bangera and Thomashow, 1996) . Pseudomonic acid is valued for its pharmaceutical properties as an antibiotic (Aldridge, 1992), whereas pyoluteorin and Phl have antifungal properties (Howell and Stipanovic, 1980; Keel et al., 1992) . A thorough understanding of the biosynthetic pathway to polyketide phytotoxins such as coronatine may ultimately lead to the development of novel compounds with altered biological properties . Thus, specific genes in the biosynthetic pathways of P . syringae phytotoxins could be deployed in other systems to develop new compounds with a wide range of activities.

Antimicrob Agents Chemother, 1998 May, 42(5), 1290 - 2
Susceptibilities of neonatal respiratory isolates of Ureaplasma urealyticum to antimicrobial agents; Matlow A et al.; Twenty-one neonatal respiratory isolates of Ureaplasma urealyticum were serotyped, and their susceptibilities to ciprofloxacin, gentamicin, chloramphenicol, erythromycin, azithromycin, and doxycycline were tested . Most patient strains were Ureaplasma urealyticum bv . parvum . Chloramphenicol, doxycycline, and azithromycin had the lowest MICs . This data may be useful when designing prophylactic or therapeutic trials of antibiotics for chronic lung disease of the newborn.

Antimicrob Agents Chemother, 1998 May, 42(5), 1239 - 44
Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk; Lampe MF et al.; The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority . Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure . To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk . C . trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times . Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted . A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C . trachomatis after 120 min of contact with the organism . The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity . On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell . Lipid activity was unaffected by the presence of 10% human blood or alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in the vagina . Our results suggest that these lipids, especially 2-O-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C . trachomatis . Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress.

J Antibiot (Tokyo), 1997 Nov, 50(11), 926 - 31
Formamicin, a novel antifungal antibiotic produced by a strain of Saccharothrix sp . I . Taxonomy, production, isolation and biological properties; Igarashi M et al.; Formamicin, an antifungal antibiotic, was isolated from the cultured broth of an actinomycete strain . The strain was isolated from a soil collected at Setagaya-ku, Tokyo, Japan, and identified as Saccharothrix sp . MK27-91F2 . Formamicin was extracted with acetone from cultured mycelia and purified by silicagel and Sephadex LH-20 column chromatographies and CPC (Centrifugal liquid-liquid Partition Chromatography) . Formamicin showed strong antimicrobial activity against phytopathogenic fungi.

J Antibiot (Tokyo), 1997 Nov, 50(11), 900 - 5
Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis . I . Taxonomy, fermentation, isolation and antimicrobial activities; Matsumoto N et al.; A new structural class of the antibiotic, epoxyquinomicins A, B, C and D were isolated from the culture broth of the strain MK299-95F4, which was related to Amycolatopsis sulphurea . Antimicrobial activity of epoxyquinomicins A and B were weak against Gram-positive bacteria, and epoxyquinomicins C and D showed almost no antimicrobial activity and no cytotoxicity . All these antibiotics showed improvement of collagen induced arthritis in vivo.

J Biochem (Tokyo), 1998 Apr, 123(4), 675 - 9
Purification, primary structure, and antimicrobial activities of bovine apolipoprotein A-II; Motizuki M et al.; We purified an antimicrobial protein of 76 residues, denoted bovine antimicrobial protein-1 (BAMP-1), from fetal calf serum using hydrophobic chromatography, gel filtration, and reverse-phase high-performance liquid chromatography . The amino acid sequence of BAMP-1 was similar to that of human apolipoprotein A-II (apo A-II), a major component of high-density lipoprotein (HDL), and the amino acid composition was almost identical to that of a previously reported candidate for bovine apo A-II . BAMP-1 was recovered from the post-HDL fraction, but not from the HDL fraction of the serum and was associated with a small amount of triglycerides (5%, w/w) . These results suggest that BAMP-1 is the bovine homologue of apo A-II and is present in almost free form in serum . BAMP-1 showed a weak growth-inhibitory activity against Escherichia coli and yeasts tested in phosphate-buffered saline (PBS).

Biofizika, 1998 Mar-Apr, 43(2), 186 - 8
{Antioxidant properties of plant extracts}; Bol'shakova IV et al.; Investigation of antioxidant properties of some plants was carried out . A group of plants exhibited antimicrobial activity was studied in detail . Efficiency of plants as antioxidants was tested by the influence of their extracts on the yield of photochemiluminescence of Gly-Trp solutions . Antioxidant properties were examined under conditions when their own absorption was minimized . Riboflavin as additional sensitizer was used in this experiment for superoxide generation . The antioxidant effect was evaluated with regard to single dose of plant extracts and their concentration in human organism . The effect decreases in the following consequence: Hypericum perforatum > Potentilla erectra > Ledum palustre > Plantago major > Salvia officinalis > Chamomilla recutita > Arctostaphylos uva.

Afr Dent J, 1995, 9, 25 - 9
Saliva and salivary gland alterations in HIV infection: a review; Matee MI et al.; HIV-1 can be recovered sporadically from whole saliva and individual salivary gland secretions, but the concentration of virus, when present, is low . Saliva possesses antiviral activity, and although virus may be found in the mouth, the mouth is not a transmission route of HIV-1 . After HIV-1 infection, salivary gland function is altered . Flow rates may decrease, and certain electrolytes and anti-microbial proteins are elevated . A proportion of patients develop severe salivary gland disease . Most patients, however, maintain adequate salivary gland function and retain ability to produce antimicrobial proteins in saliva.

Clin Chem, 1998 May, 44(5), 1129 - 40
Laboratory guidelines for monitoring of antimicrobial drugs . National Academy of Clinical Biochemistry; Hammett-Stabler CA et al.; Few antimicrobial drugs meet the requirements for therapeutic drug monitoring . Those that are monitored include the aminoglycosides (gentamicin, tobramycin, and amikacin), chloramphenicol, and in some cases, vancomycin . For these drugs, there is evidence of a relationship between serum concentration, efficacy, and/or the incidence of adverse or toxic events . Monitoring begins with the appropriate timing of collection and continues through the analytical process to the integration of all data used to guide the clinician's next decision.

Clin Ther, 1998 Mar-Apr, 20(2), 244 - 56
Cefdinir versus cephalexin for the treatment of skin and skin-structure infections . The Cefdinir Adult Skin Infection Study Group; Tack KJ et al.; Because of increasing resistance to older antimicrobial agents, newer drugs need to be evaluated for the treatment of skin and skin-structure infections (SSSIs) . This double-masked, randomized, comparative, multicenter study enrolled patients aged 13 years or older with SSSIs to receive either cefdinir 300 mg BID or cephalexin 500 mg QID for 10 days . Nine hundred fifty-two patients (474 in the cefdinir group and 478 in the cephalexin group) took part, primarily white males between 18 and 65 years of age . There were two follow-up visits, with efficacy determined at the test-of-cure visit, 7 to 16 days posttherapy . Many patients were not microbiologically assessable, primarily because of negative cultures at study admission . Patients who required surgical intervention (e.g., incision and drainage) at the site of infection more than 24 hours after the initiation of drug therapy were defined as treatment failures . Significantly more isolated pathogens were resistant to cephalexin than to cefdinir . In the 178 efficacy-assessable cefdinir-treated patients, the rate of pathogen eradication was 93% (200/215), and the rate of successful clinical response was 88% (157/178), compared with 89% (221/247) and 87% (177/204), respectively, in the 204 efficacy-assessable cephalexin-treated patients . Using confidence-interval analysis, the microbiologic and clinical response rates of the cefdinir-treated patients were statistically equivalent to those of the cephalexin-treated patients . At the follow-up visits, patients were questioned about any adverse events occurring since their previous visit . Any untoward symptom occurring during or within 2 days after completion of drug treatment was considered an adverse reaction if the investigator judged it to be definitely, probably, or possibly related to the study drug . One hundred twenty-three (26%) cefdinir-treated patients and 77 (16%) cephalexin-treated patients experienced at least one adverse reaction, a statistically significant difference . Study drug was discontinued for adverse reactions in 20 (4%) cefdinir-treated patients and 13 (3%) cephalexin-treated patients; in the two groups, 10 and 7 patients, respectively, were discontinued for diarrhea . Cefdinir taken BID was as effective as cephalexin taken QID in the treatment of mild-to-moderate SSSIs and was well tolerated by most patients . The increased antibacterial activity of cefdinir must be balanced against the higher rate of diarrhea seen in patients treated with this drug.

Am J Pathol, 1998 May, 152(5), 1247 - 58
Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract; Quayle AJ et al.; This study describes the novel localization of the antimicrobial peptide human intestinal defensin-5 (HD-5) in female genital tract epithelia . Using a 3' rapid amplification of cDNA ends (RACE) protocol, HD-5 was cloned from a vaginal epithelial cell RNA preparation, and its identity was confirmed by sequencing . Tissue samples from multiple donors were subsequently screened for HD-5 expression by reverse transcription polymerase chain reaction . HD-5 message was invariantly expressed by normal vagina and ectocervix and inflamed fallopian tube, but variably expressed by normal endocervix, endometrium, and fallopian tube (60, 64, and 29% of specimens, respectively) . Expression in endometrium was the highest during the early secretory phase of the menstrual cycle . Using immunohistochemistry and confocal microscopy, HD-5 peptide was localized in the upper half of the stratified squamous epithelium of the vagina and ectocervix, with the intensity of cellular staining increasing toward the lumen . In positive endocervix, endometrium, and fallopian tube specimens, HD-5 was located in apically oriented granules and on the apical surface of a proportion of columnar epithelial cells . Using Western blot analysis, secreted HD-5 was detected in cervicovaginal lavages, with the highest concentrations found during the secretory phase of the menstrual cycle . We hypothesize that HD-5 is an intrinsic component of the female urogenital innate immune defense system and that its expression may be modulated by hormonal and proinflammatory factors.

Biochem Biophys Res Commun, 1998 Apr 28, 245(3), 764 - 73
Bactericidal domain of lactoferrin: detection, quantitation, and characterization of lactoferricin in serum by SELDI affinity mass spectrometry; Kuwata H et al.; Lactoferricin is a bioactive peptide fragment (3196 Da) derived from lactoferrin (80 kDa) that contains the bactericidal domain and the lymphocyte receptor-binding domain of lactoferrin . Although lactoferricin has been produced from lactoferrin by proteolytic digestion in vitro, its natural occurrence and distribution in vivo are still not clear, in part because of the absence of a suitable detection means . Surface-enhanced laser desorption/ionization (SELDI) was used to detect and characterize lactoferricin by affinity mass spectrometry . Human, porcine, and bovine lactoferricin in unfractionated serum samples were found to bind specifically to ligands presenting a terminal n-butyl group . SELDI was used to detect and quantify each species of lactoferricin in a manner that was independent of the presence of intact lactoferrin, partially degraded lactoferrin, and lactoferrin peptides containing the lactoferricin peptide sequence . The limit of detection of bovine lactofericin in serum was as low as 200 pg/ml . The FKCRRWQWR-homoserine/-homoserine lactone moiety of bovine lactoferricin, which includes the complete antimicrobial center (i.e., RRWQWR), was shown to be responsible for interaction with the n-butyl group . The SELDI procedure defined here is the only molecular recognition tool known to date that is capable of distinguishing the multi-functional lactoferricin domain located within structurally related but distinct forms of lactoferrin and its metabolic fragments . Enabling the direct quantitation of lactoferricin produced in vivo opens new opportunities to evaluate lactoferrin function.

J Fr Ophtalmol, 1997, 20(10), 749 - 52
{Toxoplasmic chorioretinitis complicated by retinal detachment}; Frau E et al.; PURPOSE: To describe and analyse relationship between chorioretinal toxoplasmosis and retinal detachment . PATIENTS AND METHODS: Seven immunocompetent patients examined and treated between November 1992 and March 1996, with ocular toxoplasmic retinochoroiditis and retinal detachment . RESULTS: Of the 7 patients examined, 5 had active retinochoroiditis and 2 had typical inactive scars . Of the patients with active focus 3 had giant retinal tears, one had a posterior retinal tear and one had a retinal tear located at the edge of an atrophic scar . Of the patients with inactive lesions, one had tractional retinal detachment and the other presented with a complete retinal detachment, multiples tears and PVR . Five patients were treated by corticosteroid without antitoxoplasmic drug before they were referred . The seven patients underwent endo-ocular surgery with silicon oil or long actic gas tamponade . Three patients developed PVR and redetachment of the retina and two patients underwent further surgery . Good anatomical result was obtained in 6 patients . CONCLUSION: Retinal detachment associated with toxoplasmic retinochoroiditis is rare . However it represents a serious complication . Steroid administrated to salvage vision may then worsen the clinical course, these may be justified to reduce hypersensitivity to toxoplasma antigen, but they should be combined with an antimicrobial agent.

Q Rev Biol, 1998 Mar, 73(1), 3 - 49
Antimicrobial functions of spices: why some like it hot; Billing J et al.; Although spices have been important for centuries in food preparation throughout the world, patterns of spice use differ considerably among cultures and countries . What factors underlie these differences? Why are spices used at all? To investigate these questions, we quantified the frequency of use of 43 spices in the meat-based cuisines of the 36 countries for which we could locate traditional cookbooks . A total of 4578 recipes from 93 cookbooks was analysed . We also complied information on the temperature and precipitation in each country, the ranges of spice plants, and the antibacterial properties of each spice . These data were used to investigate the hypothesis that spices inhibit or kill food-spoilage microorganisms . In support of this is the fact that spice plant secondary compounds are powerful antimicrobial (i.e., antibacterial and antifungal) agents . As mean annual temperatures (an indicator of relative spoilage rates of unrefrigerated foods) increased, the proportion of recipes containing spices, number of spices per recipe, total number of spices used, and use of the most potent antibacterial spices all increased, both within and among countries . Likewise, the estimated fraction of bacterial species inhibited per recipe in each country was positively correlated with annual temperature . Several alternative hypotheses were considered--that spices provide macronutrients, disguise the taste and smell of spoiled foods, or increase perspiration and thus evaporative cooling; it also is conceivable that spice use provides no benefits . However, none of these four alternatives was well supported by our data . The proximate reason spices are used obviously is to enhance food palatability . But the ultimate reason is most likely that spices help cleanse foods of pathogens and thereby contribute to the health, longevity and reproductive success of people who find their flavors enjoyable.

Am Surg, 1998 May, 64(5), 402 - 7
Impact an anatomical site on bacteriological and clinical outcome in the management of intra-abdominal infections; Wilson SE et al.; The clinical and bacteriological results of treatment for 429 patients who had intra-abdominal infection were analyzed to determine whether the anatomical origin of peritonitis influenced outcome . All patients had received effective broad spectrum antimicrobial therapy and operation in four multicenter trials . The diagnoses of infection were categorized into three sites: upper gastrointestinal tract, complicated appendicitis, and lower gastrointestinal tract . Clinical response rates were excellent for complicated appendicitis and were lowest for infections related to the upper gastrointestinal tract . Bacteriological response rates were also lower for upper gastrointestinal tract organisms and were highest for isolates associated with complicated appendicitis . There were no deaths in the 213 patients who had infection associated with appendicitis . Seven deaths occurred in the 86 patients (81%) with an upper gastrointestinal site of infection, and nine deaths occurred in the 130 patients (6.5%) with lower gastrointestinal site of infection . Mortality was related to recurrent intra-abdominal infection after an unsuccessful primary operation and a serum albumin less than 25 g/l . Clinical trails of antimicrobials for intra-abdominal infection should consider stratification of patients according to these three levels of alimentary tract perforation when the site is known preoperatively . Patients who have infection secondary to previous surgery or who are malnourished represent a higher risk group even with appropriate antibiotics.

J Formos Med Assoc, 1998 Apr, 97(4), 266 - 70
One-week proton pump inhibitor-based triple therapy eradicates residual Helicobacter pylori after failed dual therapy; Sheu BS et al.; The purposes of this study were to assess the efficacy of a 1-week proton pump inhibitor (PPI)-based triple therapy after failure of dual therapy in Helicobacter pylori eradication, and to compare the effectiveness of clarithromycin and metronidazole in this regimen . Between January 1996 and March 1997, 67 patients with persistent H . pylori infection after a 2-week course of dual therapy (amoxicillin plus omeprazole) were enrolled . They were randomly assigned to receive amoxicillin (1000 mg twice daily) and omeprazole (20 mg twice daily) plus either metronidazole (500 mg twice daily) or clarithromycin (250 mg twice daily) . Endoscopy was performed in each patient to assess the status of H . pylori using the rapid urease test (CLOtest) and the histologic findings before dual therapy, after dual therapy, and after triple therapy . H . pylori isolates were tested for antibiotic resistance when triple therapy failed . The 1-week triple therapy was well tolerated in both groups with no adverse effects severe enough to cause withdrawal from the trial . Residual H . pylori was eradicated in 94% (33/35) of patients in the clarithromycin group and 84% (27/32) in the metronidazole group; the difference was not statistically significant . All seven patients in whom triple therapy failed were infected with metronidazole-resistant isolates and two also had clarithromycin-resistant isolates . This 1-week triple therapy is safe and effective in eradicating residual H . pylori after dual therapy failure . Failure of the rescue regimen is related to antimicrobial agent resistance . Because of the high metronidazole resistance rate in Taiwan, clarithromycin appears to be more promising than metronidazole for the control of H . pylori.

J Nat Prod, 1998 Apr, 61(4), 548 - 50
Agelasines H and I, 9-methyladenine-containing diterpenoids from an Agelas sponge; Fu X et al.; Two new diterpenes possessing a 9-methyladeninium substituent, agelasines H (5) and I (6), along with five related known ones, 1-4 and 7, were isolated from a sponge, Agelas sp . The structures of the new compounds were determined from spectral data . Compounds 2-4, 6, and 7 exhibited varying degrees of antimicrobial activity.

Endocrinology, 1998 May, 139(5), 2253 - 64
Novel sites of adrenomedullin gene expression in mouse and rat tissues; Cameron VA et al.; Adrenomedullin (AM) was originally identified in pheochromocytoma tissue and was characterized as a hypotensive peptide . The tissue distribution and cellular localization of AM messenger RNA (mRNA) were determined in mouse and rat tissues by in situ hybridization . Three probes were used: two nonoverlapping probes to the pro-AM N-terminal 20 peptide (PAMP) and AM peptide regions of mouse pro-AM, and a larger complementary DNA (cDNA) probe spanning both the PAMP- and AM peptide-coding regions . The most intense expression of AM mRNA was in endometrium and epithelial cells lining the uterus and mouse adrenal medulla . Moderate levels of expression were detected in kidney glomerulus and cortical distal tubules, ovarian corpus luteum and follicles, epithelial cells lining the bronchioles, cardiac atrium and ventricle, posterior pituitary (particularly in female rats), stomach, small intestine (microvilli, mucosa and submucosa), spleen, and pancreas . Lower levels were observed in pulmonary alveoli, anterior pituitary, and submandibular gland . No expression was detected in the testis, thymus, skeletal muscle, or liver . The localization of AM mRNA in epithelial cells lining the uterus, bronchioles, and gastrointestinal tract indicates novel roles for AM, possibly as an antimicrobial agent . The strong expression of AM in uterus, ovary, and posterior pituitary suggests that AM plays a role in female reproduction.

Biochim Biophys Acta, 1998 Mar 13, 1370(2), 218 - 34
The aminosterol antibiotic squalamine permeabilizes large unilamellar phospholipid vesicles; Selinsky BS et al.; The ability of the shark antimicrobial aminosterol squalamine to induce the leakage of polar fluorescent dyes from large unilamellar phospholipid vesicles (LUVs) has been measured . Micromolar squalamine causes leakage of carboxyfluorescein (CF) from vesicles prepared from the anionic phospholipids phosphatidylglycerol (PG), phosphatidylserine (PS), and cardiolipin . Binding analyses based on the leakage data show that squalamine has its highest affinity to phosphatidylglycerol membranes, followed by phosphatidylserine and cardiolipin membranes . Squalamine will also induce the leakage of CF from phosphatidylcholine (PC) LUVs at low phospholipid concentrations . At high phospholipid concentrations, the leakage of CF from PC LUVs deviates from a simple dose-response relationship, and it appears that some of the squalamine can no longer cause leakage . Fluorescent dye leakage generated by squalamine is graded, suggesting the formation of a discrete membrane pore rather than a generalized disruption of vesicular membranes . By using fluorescently labeled dextrans of different molecular weight, material with molecular weight </=4000 g/mol is released from vesicles by squalamine, but material with molecular weight >/=10,000 is retained . Negative stain electron microscopy of squalamine-treated LUVs shows that squalamine decreases the average vesicular size in a concentration-dependent manner . Squalamine decreases the size of vesicles containing anionic phospholipid at a lower squalamine/lipid molar ratio than pure PC LUVs . In a centrifugation assay, squalamine solubilizes phospholipid, but only at significantly higher squalamine/phospholipid ratios than required for either dye leakage or vesicle size reduction . Squalamine solubilizes PC at lower squalamine/phospholipid ratios than PG . We suggest that squalamine complexes with phospholipid to form a discrete structure within the bilayers of LUVs, resulting in the transient leakage of small encapsulated molecules . At higher squalamine/phospholipid ratios, these structures release from the bilayers and aggregate to form either new vesicles or squalamine/phospholipid mixed micelles .

Eur Respir J, 1998 Jan, 11(1), 104 - 11
Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis; Ashitani J et al.; Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins . Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB) . Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults . The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects . DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls . In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8 . Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells . In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8 . Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF . Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.

AIDS Res Hum Retroviruses, 1998 Apr, 14 Suppl 1, S5 - 10
Heterosexual transmission of human immunodeficiency virus type 1 (HIV): interactions of conventional sexually transmitted diseases, hormonal contraception and HIV-1; Plummer FA; The interactions between HIV-1 and other viral sexually transmitted infections (STI) are complex . The presence of ulcerative and nonulcerative STD increase susceptibility of exposed individuals to HIV-1 infection by several folds . In HIV-1 infected individuals, STD increase genital tract shedding of HIV-1 and enhance the infectivity of these individuals . STD have also recently been shown to increase plasma viremia either directly or through altering the cytokine milieu, which may both increase infectivity and result in more rapid HIV-1 disease progression . HIV-1 infection in turn has effects on susceptibility to other STD as well as increasing the serverity of some infections and possibly reducing the response to antimicrobial therapy . In addition, other potential risk factors for sexual transmission of HIV-1, such as hormonal contraception in women and lack of circumcision in men, may operate partly through effects on enhancing susceptibility to STD . The mutual enhancement of transmission of HIV-1 and other STD that has fueled HIV-1 epidemics worldwide, offers the opportunity for intervention . The effectiveness of this approach has recently been demonstrated in a trial in Mwanza, Tanzania, where provision of effective treatment for STD resulted in a 40% decline in HIV-1 incidence . The implementation of effective STD management may do much to slow the spread of HIV-1.

Br J Dermatol, 1998 Mar, 138(3), 467 - 76
Patch testing with preservatives, antimicrobials and industrial biocides . Results from a multicentre study; Schnuch A et al.; Preservatives are biologically reactive substances, and their allergenic potential has been known for a long time . This study examined the role of different preservatives in a large number of patients with suspected allergic contact dermatitis . Patch test data and data from the patients' history were collected from the 24 departments participating in the Information Network of Departments of Dermatology from 1 January 1990 to 31 December 1994 . Patch test data from 28,349 patients tested with preservatives of the standard series (SS), from 11,485 patients tested additionally with a preservative series (PS), and from 1787 patients tested with an industrial biocide tray (IB) were evaluated . Sensitization rates (standardized) of the SS preservatives were all > 1%, with thiomersal rating highest (5.3%), the parabens lowest (1.6%), and the remainder (chlormethylisothiazolinone/methylisothiazolinone, formaldehyde and methyldibromoglutaronitrile/phenoxyethanol (MDBGN/PE)) in the range of 2% . The most important allergens of the PS were, in women, alkylaminobenzoate (contained in milking fat) (2.5%), MDBGN/PE (2.2%), benzalkonium chloride (1.8%), chloracetamide (1.4%), diazolidinyl urea (1.3%), octylgallate (1.2%) and Bronopol (1.1%) . In men rates differed only with regard to alkylaminobenzoate (0.9%) . Patients tested with the IB series reacted most often to methylene-bis-thiocyanate (5%), but with a reaction index of -0.7, many reactions were most probably false positives . A further seven preservatives, mostly formaldehyde-releasers used in cutting fluids, gave sensitization rates of between 1% and 3% . Glutaraldehyde, not contained in the series but often tested additionally, showed a remarkable increase in sensitization during the study period . Health care personnel were frequently affected . Altogether, this study identified areas of concern within the different groups of preservatives . The overall impact of most of the preservatives on public health seems to be low, but for diagnostic reasons preservatives must be included in patch test series.

Br J Cancer, 1998 Apr, 77(8), 1294 - 9
Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost; Lee SM et al.; In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor (G-CSF, filgrastim) following peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23 consecutive patients aged less than 60 years with poor-prognosis, high-grade non-Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between May 1993 and September 1995 . Patients were randomized to receive either PBPC alone (n = 12) or PBPC+G-CSF (n = 11) after HDCT with busulphan and cyclophosphamide . G-CSF (300 microg day{-1}) was given from day +5 until recovery of granulocyte count to greater than 1.0 x 10(9) l(-1) for 2 consecutive days . The mean time to achieve a granulocyte count > 0.5 x 10(9) l(-1) was significantly shorter in the G-CSF arm (9.7 vs 13.2 days; P<0.0001) as was the median duration of hospital stay (12 vs 15 days; P = 0.001) . In addition the recovery periods (range 9-12 vs 11-17 days to achieve a count of 1.0 x 10(9) l{-1}) and hospital stays (range 11-14 vs 13-22 days) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median . There were no statistically significant differences between the study arms in terms of days of fever, documented episodes of bacteraemia, antimicrobial drug usage and platelet/red cell transfusion requirements . Taking into account the costs of total occupied-bed days, drugs, growth factor usage and haematological support, the mean expenditure per inpatient stay was pound sterling 6500 (range pound sterling 5465-pound sterling 8101) in the G-CSF group compared with pound sterling 8316 (range pound sterling 5953-pound sterling 15,801) in the group not receiving G-CSF, with an observed mean saving of 1816 per patient (or 22% of the total cost) in the G-CSF group . This study suggests that after HDCT and PBPC rescue, the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay . Furthermore, and despite the additional costs for G-CSF, these clinical benefits are not translated into increased health care expenditure.

J Antimicrob Chemother, 1998 Mar, 41 Suppl B, 29 - 35
Synergic interactions of macrolides and proton-pump inhibitors against Helicobacter pylori: a comparative in-vitro study; Malizia T et al.; Thirty-eight clinical strains of Helicobacter pylori were isolated from patients with chronic gastritis and gastroduodenal ulceration, and their susceptibility to macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin) in combination with proton-pump inhibitors (lansoprazole and omeprazole) and bismuth subcitrate was assayed . Chequerboard titration was used to analyse the results of antimicrobial interactions and showed that the activity of macrolides was enhanced by combining them with lansoprazole, omeprazole or, to a lesser extent, bismuth subcitrate . While the interactions between erythromycin and the proton-pump inhibitors or bismuth subcitrate were always additive, the combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H . pylori strains, respectively . These results may, in part, account for the enhanced clinical efficacy of macrolides administered with proton-pump inhibitors in the treatment of H . pylori-associated diseases.

Aust Vet J, 1998 Jan, 76(1), 25 - 31
Role of prokinetic drugs for treatment of postoperative ileus in the horse; Dart AJ et al.; All horses undergoing coeliotomy for an acute abdominal crisis are at risk of developing ileus and should receive therapy aimed at promoting gastrointestinal function by restoring fluid and electrolyte balance . Adequate analgesia and prevention against peritonitis, bacteraemia and endotoxaemia should be provided . Horses that at the time of surgery have a strangulating or non-strangulating small intestinal obstruction should be considered to be at greater risk of developing a persistent ileus that is refractory to treatment than those horses with lesions involving the large intestine . In horses considered to be at greater risk of developing a persistent ileus, the use of prokinetic agents should be considered . Agents that may be used to improve gastrointestinal motility include adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists, somatostatin analogues and local anaesthetics . There are limited studies into the use of these agents in the horse . Until further research provides more information on motility disorders following intestinal surgery and the efficacy of prokinetic agents in this species, only selective use of some of these drugs can be recommended.

Chem Biol, 1998 May, 5(5), 293 - 8
A ligand-mediated dimerization mode for vancomycin; Loll PJ et al.; BACKGROUND: Vancomycin and related glycopeptide antibiotics exert their antimicrobial effect by binding to carboxy-terminal peptide targets in the bacterial cell wall and preventing the biosynthesis of peptidoglycan . Bacteria can resist the action of these agents by replacing the peptide targets with depsipeptides . Rational efforts to design new agents effective against resistant bacteria require a thorough understanding of the structural determinants of peptide recognition by vancomycin . RESULTS: The crystal structure of vancomycin in complex with N-acetyl-D-alanine has been determined at atomic resolution . Two different oligomeric interactions are seen in the structure: back-to-back dimers, as previously described for the vancomycin-acetate complex, and novel face-to-face dimers, mediated largely by the bound ligands . Models of longer, naturally occurring peptide ligands may be built by extension of N-acetyl-D-alanine . These larger ligands can form an extensive array of polar and nonpolar interactions with two vancomycin monomers in the face-to-face configuration . CONCLUSIONS: A new dimeric form of vancomycin has been found in which two monomers are related in a face-to-face configuration, and bound ligands comprise a large portion of the dimer interface . The relative importance of face-to-face and back-to-back dimers to the antimicrobial activity of vancomycin remains to be established, but face-to-face interactions appear to explain how increased antimicrobial activity may arise in covalent vancomycin dimers.

Eur J Biochem, 1998 Apr 1, 253(1), 221 - 8
Solution structure of the antimicrobial peptide ranalexin and a study of its interaction with perdeuterated dodecylphosphocholine micelles; Vignal E et al.; Ranalexin, a 20-residue peptide isolated from the skin of the bullfrog Rana catesbeiana displays antimicrobial activity . This peptide contains two cysteine residues in positions 14 and 20 linked by a disulphide bridge . Ranalexin was chemically synthesised and close antimicrobial activities were measured for the reduced and oxidised forms . The solution structure of ranalexin was determined by using circular dichroism, proton NMR spectroscopy and molecular modelling techniques . The reduced and oxidised forms of ranalexin are mainly unstructured in water but display an alpha-helical structure spanning residues 8-15 and 8-17, respectively, in a trifluoroethanol/water mixture (3:7, by vol.) . Ranalexin was found to interact with micelles of dodecylphosphocholine and to adopt a similar helical structure . Moreover, slow-exchanging amide protons located on the same side of the helix suggest that the hydrophobic face of the helix lies on the micelle surface . Hydrophobic residues of the poorly structured N-terminal part which are important for the biological activity are also involved in the interaction with micelles . Taken together, the results suggest that the disulphide bond does not strongly affect either the conformation or the antimicrobial activity of ranalexin.

Med Hypotheses, 1998 Mar, 50(3), 219 - 26
Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation; Romanovsky AA et al.; Entering both the old dispute (whether fever is adaptive or maladaptive) and its more recent modification (whether hypothermia is protective or detrimental in systemic inflammation), we suggest a new solution . We hypothesize that fever and hypothermia represent two different strategies of fighting systemic inflammation, each developed as an adaptive response to certain conditions, and each beneficial under these conditions . The antimicrobial and immunostimulating benefits of a high body temperature could be easily offset by its high energy cost . Fever, therefore, is protective only when there is no immediate threat of a substantial energy deficit . Hypothermia, on the other hand, constitutes a response aimed at energy conservation and, as such, is beneficial exactly under the conditions of a substantial energy deficit . The two thermoregulatory responses represent two complementary strategies of survival in systemic inflammation: fever ensures the active attack against the pathogen; hypothermia secures the defense of the host's vital systems . The importance of each response's contribution to the whole campaign depends on the severity of the pathogenic insult, premorbid pathology, and current conditions (stress, nutrition, ambient temperature, etc.).

Neurol Clin, 1998 May, 16(2), 419 - 47
Infections of the nervous system; Pruitt AA; Epidemiologic trends causing infections of the nervous system remain a significant source of morbidity and mortality one half-century after the introduction of penicillin . This article outlines common causes of bacterial meningitis, aseptic meningitis syndrome, encephalitis, abscess, spinal cord syndromes, and cranial and peripheral nerve problems . Recommendations for diagnostic evaluation and both empiric and definitive antimicrobial therapy are offered; controversial management issues are also discussed . The protean manifestations of varicella-zoster virus and Lyme diseases are outlined . In addition, special considerations in the immunocompromised host, including organ transplant recipients, cancer patients, and HIV-positive persons are explained, and antimicrobial therapy is discussed.

Am J Gastroenterol, 1998 Apr, 93(4), 562 - 8
Cost-effectiveness of noninvasive testing and treatment strategies for H . pylori infection in children with dyspepsia; Vakil N et al.; OBJECTIVE: We sought to model the cost-effectiveness of endoscopy, noninvasive testing and treatment strategies for Helicobacter pylori infection in children with recurrent abdominal pain in two health care systems, those of the United States and Finland . METHODS: Initial serological testing and treatment was compared to empirical treatment with antimicrobials, endoscopy with rapid urease testing, and 13C urea breath testing . Key assumptions and ranges were obtained from the published literature . Costs were determined for the acquisition of various tests and actual reimbursement figures were used for procedural costs . RESULTS: The disease management costs were very similar for both endoscopy ($643.00) and serology ($646.00) in the United States . In Finland, endoscopy ($173.00) was less expensive than serology ($192.00) . The 13C urea breath test was the most expensive procedure in the United States . Sensitivity analysis demonstrated that serological testing became the preferred path if its cost was < $42 in the United States . Empirical treatment of children with dyspepsia was not cost-effective in either country . Sensitivity analysis showed that when prevalence of infection was > 53% in children with recurrent abdominal pain, empirical therapy with endoscopy reserved for failures was the optimal path . CONCLUSIONS: In developed countries like the United States and Finland, significant cost savings are unlikely with an initial test and treat strategy based on serology . Noninvasive testing and treatment of H . pylori infection can be cost-effective in populations with highly prevalent rates of infection.

Am J Gastroenterol, 1998 Apr, 93(4), 553 - 61
How do clinicians practicing in the U.S . manage Helicobacter pylori-related gastrointestinal diseases? A comparison of primary care and specialist physicians; Breuer T et al.; OBJECTIVES: We sought to examine the extent to which physicians recognize H . pylori as a causal agent in peptic ulcer disease or as a potential cofactor in other gastrointestinal diseases, and to observe how this knowledge has influenced diagnostic and therapeutic practices . METHODS: We used a national mail survey in the U.S . between February and May of 1996, querying 5994 U.S . physicians (family/general practitioners {FPs}, internists {IMs}, and gastroenterologists) selected at random from three different membership databases of professional associations . RESULTS: The response rate was 52% . More than 95% of physicians who treat symptoms empirically would prescribe acid suppressant therapy rather than anti-H . pylori therapy . Between 43% and 66% of physicians, varying in frequency by medical specialty, would treat the infection in H . pylori-positive patients with nonulcer dyspepsia . In confirmed peptic ulcer disease, between 88% and 100% of physicians would treat the H . pylori infection, depending on the physician group and whether or not the presentation of an ulcer was recurrent . Although 103 distinct anti-H . pylori regimens were reported, 89% of the gastroenterologists and 70% of the primary care physicians (PCPs) used combinations of antimicrobials with reported cure rates of at least 80% . CONCLUSIONS: General knowledge regarding H . pylori-associated diseases was widespread among primary care physicians and gastroenterologists . However, anti-H . pylori therapies judged ineffective were reported as the first choice regimen by 5% of gastroenterologists and 18% of primary care physicians . Gastroenterologists appear to implement the latest scientific developments in the field rapidly whereas PCPs manifest a delayed response, due to either insufficient knowledge or to other factors influencing their approach to treatment.

Mil Med, 1998 Apr, 163(4), 198 - 201
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 increases, 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 period of heightened surveillance for emerging infectious diseases is the ability to differentiate between natural and intentional outbreaks . Certain attributes of a disease outbreak, although perhaps not pathognomonic for a biological attack when considered singly, may combine to provide convincing evidence of 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.

Folia Med (Plovdiv), 1997, 39(4), 93 - 7
Acute renal failure--etiologic and therapeutic considerations . A five-year experience at a single institution; Dimitrakov D et al.; In the present study we highlight the epidemiology, etiologic spectrum, and evaluation of ARF in adults . We then expand on the pathophysiologic mechanisms of renal failure and discuss the rationale for current therapeutic strategies in ARF patients . A total of 79 patients (45 male, female 34), aged 18-75 years (median age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years (January 1990 through October 1995) . Emergency hemodialysis sessions following an acute anuric episode were instituted in 39 cases (49.3% of all patients) . The median number of hemodialysis procedures per patient treated at our institution was 3.2 +/- 1.9 . The total number of acute interstitial nephritis-associated ARF was 40 . In 30 of them (75%) the acute renal insult included a combination of several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted from a combined therapeutic regimen and in the remaining 5 (12.5%) from the application of a single drug . Acute interstitial nephritis developed in 2 patients following a viral infection . In the hemodialysis-treated ARF group 12 patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented with renal impairment for an unspecified period of time preceding the development of overt ARF . In a subset of this group of patients, ARF occurred in 7 patients (17.95%) following an urologic intervention, in 8 patients (20.51%) as a consequence of thermal or mechanical trauma or intoxication and in 3 cases (7.69%) it resulted from fever of unknown origin . Three patients with postoperative peritonitis and 4 other (10.26%) with postoperative complications were encountered in our series . No cases of septic abortion-related or obstetric-related ARF were recorded . 92.3% of all hemodialysis-treated patients seen at our Institution had received a combination of antibiotics and only 2 patients had been pre-treated with a single antimicrobial agent . Our results underscore the strong tendency towards diversity in the etiologic spectrum of clinical entities causing ARF and the increase in the number of acute interstitial nephritis . These factors highlight the importance of precise dosing and administration of drugs, especially antibiotics, as well as the duration of antibiotic treatment.

Rev Rhum Engl Ed, 1998 Mar, 65(3), 181 - 6
Iliopsoas bursopathies . A review of twelve cases; Ginesty E et al.; Synovial cysts are far less common at the hip than at the knee and usually occur in patients whose hip cavity communicates with the iliopsoas bursa . We report 12 cases of enlargement of the iliopsoas bursa, nine men and three women, with a mean age of 48 years . The six patients with septic bursitis had severe symptoms similar to those seen in septic arthritis of the hip . Chronic pain with or without a palpable inguinal swelling was the main symptom in the six remaining patients, some of whom had compression of neighboring structures making the diagnosis more difficult . Ultrasonography is the best first-line investigation in patients with an inguinal swelling . Computed arthrotomography with examination of the synovial fluid or magnetic resonance imaging should be performed as a confirmatory diagnostic test . Our series provides evidence of the efficacy of appropriate antimicrobial therapy in septic cases and of corticosteroid injections into the bursa or hip cavity in nonseptic cases.

Langenbecks Arch Chir Suppl Kongressbd, 1997, 114, 953 - 5
{Aspects of calculated and controlled antibiotic therapy}; Rodloff AC; Strategies for selection of antimicrobial agents may include estimation of the most appropriate agent (empirical therapy), or planned escalation or de-escalation therapy . Severe and life-threatening infections such as peritonitis have a particularly poor prognosis if the initial therapy fails . Hence, in these cases a de-escalation therapy employing broad spectrum agents with proven high efficacy should be employed, and selection pressure arguments and cost considerations should be immaterial . After 48 to 72 hours, this initial therapy should be reconsidered (de-escalated to less powerful agents), especially in light of the microbiological test results.

Oral Microbiol Immunol, 1997 Dec, 12(6), 366 - 71
In vitro antimicrobial susceptibility of periodontopathic Actinobacillus actinomycetemcomitans to roxithromycin and erythromycin; Piccolomini R et al.; The in vitro minimal inhibitory concentrations (MIC) and minimal bactericidal concentration (MBC) of roxithromycin and erythromycin against Actinobacillus actinomycetemcomitans were evaluated . Sixty-seven different A . actinomycetemcomitans isolated from periodontal pockets of 101 subjects with different forms of early-onset and adult periodontitis and three reference strains of A . actinomycetemcomitans (ATCC 29522, ATCC 29523, and NCTC 9710) were included in this study . Erythromycin showed poor in vitro activity against A . actinomycetemcomitans; roxithromycin, on the contrary, exhibited good in vitro activity . Moreover, roxithromycin showed the best in vitro antimicrobial activity against 17 serotype a and 12 serotype c subpopulations of A . actinomycetemcomitans; against 38 serotype b subpopulation of A . actinomycetemcomitans, roxithromycin was consistently active . Roxithromycin exhibited MBC values usually equal to, or one-fold higher than MIC values . All the MBC values of erythromycin were three- to four-fold higher than the respective MIC result . Since roxithromycin is characterized by high concentrations in serum and good penetration and diffusion into gingival tissue, it could be expected to pass into the gingival crevicular fluid at levels sufficiently high to inhibit A . actinomycetemcomitans in vivo . These data indicate that roxithromycin might be a potential candidate for therapeutic trials in patients with A . actinomycetemcomitans-associated periodontitis.

Haematologica, 1998 Mar, 83(3), 231 - 6
Prior treatment with alpha-interferon does not adversely affect the outcome of allogeneic BMT in chronic phase chronic myeloid leukemia; Zuffa E et al.; BACKGROUND AND OBJECTIVE: Controlled clinical trials have shown that Interferon-alpha (IFN-alpha) is able to control myeloid proliferation and to suppress the Ph+ clonal hemopoiesis in early chronic phase chronic myeloid leukemia (CML): a growing number of patients are treated with this agent from diagnosis . However, if a CML patient has an HLA-identical sibling, bone marrow transplant (BMT) represents the best choice of treatment . Since IFN-alpha is known to modify the immunologic response and to increase marrow fibrosis, information is needed on the outcome of patients transplanted after IFN-alpha treatment . DESIGN AND METHODS: We analyzed retrospectively 32 Ph+ CML patients submitted to BMT in the last 6 years in Institute "Seragnoli" . All the patients were in 1st chronic phase, their median age was 37 years, the donors were HLA-identical (27/32) or 1 Ag-mismatched (5/32) siblings . Big BuCy was the conditioning regimen employed for all and GVHD prophylaxis was based on CsA in 4 patients and Csa+MTX in 28 patients; all patients received homogeneous pre and post-transplant supportive care, antimicrobial and antiviral prophylaxis . These patients were divided into 2 groups according to the treatment before BMT: 16 received IFN from diagnosis to BMT (mean dose 6.9 MU/daily) for at least 6 mos (mean 23 mos, range 8-75) and 16 received chemotherapy alone (hydroxyurea {HU}) . RESULTS: Hematological recovery was comparable in the two groups: time to 0.5 x 10(9)/L PMN was 20.5 days (range 11-32) in the IFN group and 20 days (range 10-32) in the HU group; time to 50 x 10(9)/L platelets was 28 days (range 20-117) in the IFN group and 27 days (range 20-112) in the HU group . The incidence of acute GVHD was not different in the two groups for any grade of the disease; in patients who survived more than 100 days, chronic GVHD occurred in the two groups with the same frequency . Seven patients died of transplant related mortality (TRM), 4 in the IFN group and 3 in the HU group . Hematological relapse was observed in only one case in the HU group; no cytogenetic relapse occurred . Disease free survivals at 7 years are 61% and 72%, respectively; the difference is not significant . INTERPRETATIONS AND CONCLUSIONS: Notwithstanding the low number of patients included in this study, the data reported here confirm that prior treatment with alpha-IFN does not adversely affect transplant outcome.

Int J Antimicrob Agents, 1998 Feb, 9(4), 239 - 53
Subgingival controlled release of antimicrobial agents in the treatment of periodontal disease; Southard GL et al.; Local drug delivery of antimicrobics by sustained release delivery systems can be used to treat periodontal disease . Advantages of these systems may include biodegradation of the system, maintaining high levels of antibiotic in the gingival crevicular fluid (GCF) for a sustained period of time and ease of use with high patient acceptance . This review will identify human in vivo clinical and microbiological studies . Sustained release formulations, application methods, clinical results and microbiological effects are discussed.

Folia Microbiol (Praha), 1998, 43(1), 7 - 14
Biological effects of macrotetrolide antibiotics and nonactic acids; Zizka Z; Published results as well as patent applications on biological effects of macrotetrolides and nonactic acids are reviewed . Their antimicrobial, antiprotozoan (coccidiostatic), antiparasitic (anthelminthic), insecticidal and acaricidal (miticidal) effects and also newly described immunosuppressive and plant growth stimulating activities are described . Both theoretical papers and practical applications including the effects of macrotetrolides on the environment are included; a particular target organism and precise dosage (e.g . LD50) are reported, in agreement with the original papers . It appears that macrotetrolides and their homologs are very prospective bioactive compounds that find application in agriculture, forestry, human and veterinary medicine while their negative effects on the environment are restricted to a minimum (biological quality of soil and water etc.).

J Gen Virol, 1998 Apr, 79 ( Pt 4), 731 - 40
Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression; Wachinger M et al.; Antimicrobial peptides are effectors of innate immunity, providing their hosts with rapid non-specific defence against parasitic invaders . In this report, the effects are assessed of two well-characterized antimicrobial amphipathic peptides (melittin and cecropin) on human immunodeficiency virus 1 (HIV-1) replication and gene expression in acutely infected cells at subtoxic concentrations . Production of infectious, cell-free virus was inhibited in a dose-dependent manner, with ID50 values in the range 0.9-1.5 microM for melittin and 2-3 microM for cecropin . Analysis of the effect of melittin on cell-associated virus production revealed decreased levels of Gag antigen and HIV-1 mRNAs . Transient transfection assays with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that melittin has a direct suppressive effect on activity of the HIV LTR . HIV LTR activity was also reduced in human cells stably transfected with retroviral expression plasmids for the melittin or cecropin gene . It is concluded that antimicrobial peptides such as melittin and cecropin are capable of inhibiting cell-associated production of HIV-1 by suppressing HIV-1 gene expression.

Clin Exp Metastasis, 1998 Apr, 16(3), 217 - 25
Chemically modified tetracyclines inhibit human melanoma cell invasion and metastasis; Seftor RE et al.; Recent work has shown that chemically modified tetracyclines (CMTs) are potent inhibitors of matrix metalloproteinase (MMP) activity, both in vitro and in vivo, which is distinct from their antimicrobial activities (Golub et al . Crit Rev Oral Biol Med, 2, 297-321, 1991; Ryan et al . Curr Opin Rheumatol, 8, 23847, 1996) . The process of tumor cell invasion requires MMP-mediated degradation of extracellular matrix barriers as a key step in the metastasic cascade . In this study, we examined the effect(s) of doxycycline and CMTs on extracellular levels of gelatinase A and B activity from a highly invasive and metastatic human melanoma cell line C8161, and correlated these observations with changes in the cells' biological behavior in an in vitro invasion assay and in an in vivo SCID mouse model . The results indicate that coincident with the ability of these compounds to differentially suppress extracellular levels of gelatinase activity, C8161 cells treated with doxycycline, CMT-1, CMT-3, or CMT-6 were less invasive in vitro in a dose-dependent manner (3-50 microg/ml) . Furthermore, data derived from the in vivo model indicate that SCID mice dosed orally with CMT-1 or CMT-3 contained a reduced number of lung metastases following i.v . injection of C8161 cells via tail vein inoculation . These observations suggest that careful screening of different CMTs could lead to the identification of compounds which suppress the formation and magnitude of metastases associated with certain cancers, and if used as an adjunct to other treatment regimes, lead to greater efficacy in the treatment of metastatic cancers.

Burns, 1997 Nov-Dec, 23(7-8), 608 - 14
Cryopreserved cadaveric allografts for treatment of unexcised partial thickness flame burns: clinical experience with 12 patients; Eldad A et al.; Partial thickness burns (PTB) usually heal within 3 weeks . Prevention of infection and desiccation of the wounds are crucial for optimal healing . Early tangential excision of the burn eschar and allografting prevent deepening of the burns, and are therefore advocated for treatment with the best functional and aesthetic results . For superficial partial thickness burns (SPTB) conservative use of topical antimicrobial agents with frequent dressing changes are implemented . We compared the conservative treatment for PTBs and SPTBs to grafting cryopreserved cadaveric allografts with no prior excision . Twelve patients with flame PTB areas were allografted after mechanical debridement without excision of the burn wounds . The allografts were cadaveric skin cryopreserved by programmed freezing and stored at -180 degrees C for 30-48 months . Matching burns for depth and area were treated with silver sulfadiazine (SSD) one to two times daily until healing or debridement and grafting were required . It was found that 80 per cent of the cryopreserved allografts adhered well and 76 per cent of the treated areas healed within 21 days, whereas only 40 per cent of the SSD-treated burns healed within 21 days . Partial thickness burns can be treated successfully with viable human allografts (cryopreserved cadaveric skin) with no prior surgical excision . The burn wounds heal well within 3 weeks . For deep partial thickness burns (DPTB) treatment with allografts has no advantage if they have not been previously excised.

Br Poult Sci, 1998 Mar, 39(1), 42 - 6
Effectiveness of two fluoroquinolones for the treatment of chronic respiratory disease outbreak in broilers; Sumano LH et al.; 1 . Chronic respiratory disease (CRD) caused by Mycoplasma synoviae in association with Escherichia coli is the disease most frequently encountered in poultry in Mexico . 2 . Differences of antimycoplasmal activity, pharmacokinetics and cost among fluoroquinolones were the impetus for this clinical evaluation of efficacy of enrofloxacin and norfloxacin-nicotinate in broilers with CRD . 3 . A total of 99,600 broilers, naturally infected with M . synoviae and E . coli, were treated with enrofloxacin (10 mg/kg/d for 3 d) (n = 49,800) or norfloxacin-nicotinate (20 mg/kg/d for 3 d) (n = 49,800) . 4 . Based on survivor analysis, there were no significant differences of efficacy of the 2 drugs . Survivor probabilities were above 0.99 . 5 . These results indicate that enrofloxacin and norfloxacin-nicotinate are efficacious for treatment of CRD . Questions remaining to be answered by other studies include: public health concern about the use of fluoroquinolones for the treatment of CRD; clinical superiority of one of these drugs on the basis of an attribute other than antimicrobial activity, such as cost:benefit ratio or ability to prevent bacterial resistance . 6 . Clinical efficacy is not a relevant variable in assessing whether norfloxacin-nicotinate or enrofloxacin should be used for the treatment of CRD associated with E . coli in broilers.

Sci Prog, 1998, 81 ( Pt 1), 35 - 68
Plants under attack II; Strange RN; In many diseases of plants there is a well defined genetic relationship between host and pathogen, the host possessing resistance genes and the pathogen possessing avirulence genes . Where these are cognate their products interact and trigger a variety of resistance responses, resulting in an incompatible interaction . Where they are not cognate the pathogen is not recognised and invades the host causing a compatible interaction . A few resistance genes and a larger number of avirulence genes have been cloned and this information has afforded us new perspectives of the recognition phenomenon itself and the means by which virulent pathogens avoid being recognised . Mechanisms of resistance range from preformed antimicrobial compounds to a series of components that are induced as a response to microbial challenge . Most of these induced reactions are preceded by and may be triggered by an oxidative burst which results in the cross-linking of cell wall proteins and also causes the death of one to several cells . This localized death of host cells, termed the hypersensitive response, provides an explanation for resistance to obligate parasites which require living host tissue but not for resistance to facultative parasites which colonise dying or dead tissue . However, the hypersensitive response appears to be intimately involved with several other defence responses such as the synthesis and accumulation of phytoalexins, lignification and the production of hydrolase enzymes that attack the invader . Salicylic acid has proved fundamental to the effecting of these defence responses and also to the phenomenon of systemic acquired resistance whereby a previous challenge from a pathogen induces the expression of enhanced resistance to a second challenge by the same or another organism . Despite these sophisticated defences plants still succumb to attack . Two of the weapons to which they are vulnerable and which are produced by many successful pathogens are toxins and enzymes . In some instances an understanding of these has pointed to novel methods of control supplementary to that obtained by conventional breeding for resistance.

Indian J Exp Biol, 1997 Nov, 35(11), 1233 - 6
Effect of mycotoxins isolated from Penicillium nigricans on glucose-6-phosphate dehydrogenase; Majumder UK et al.; A new mycotoxin product (NMP) was isolated from the culture of mutated wild strain of P . nigricans which is less toxic and has sterol derivative . NMP (LD50 > 1 g/kg) showed antimicrobial and antineoplastic activities and does not affect the hematological parameters like RBC count and hemoglobin . It maintained normal blood glucose level by increasing the enzyme activity of glucose-6-phosphate dehydrogenase (EC-1.1.1.49; G-6-PDH) by 30% . It also maintained the normal ion balance in the blood of mice . NMP decreased Km value of glucose-6-phosphate dehydrogenase and thus increased substrate affinity of the enzyme . Reduction of toxicity of NMP has been well explained by higher activity of G-6-PDH which is highly specific for production of NADPH.

Rev Hosp Clin Fac Med Sao Paulo, 1997 Jul-Aug, 52(4), 209 - 16
{Antibiotic prophylaxis in oncologic surgery}; Velasco E et al.; Perioperative antibiotic administration can decrease surgical morbidity, shorten hospitalization, while lowering the overall costs attributable to infections . Its use in surgery is widespread and often inappropriate . In this study, the authors evaluate the guidelines for selection and use of prophylactic antibiotics in surgical cancer patients at the Hospital of Cancer in Rio de Janeiro, Brazil . During 36 non-consecutive months, 1681 cancer patients submitted to surgical procedures were prospectively followed-up by members of the Hospital Infection Control Committee . The overall surgical site infection (SSI) and mortality rates were 17.7% and 4.8% respectively . Prophylactic antibiotics were used in 1262 elective surgeries (75.1%), and their use was not considered to be in accordance with the recommended protocol in 37.6% of the cases . The inadequate antimicrobial prophylaxis resulted in higher incidence of SSI than did prophylaxis in according to the protocol (21.7% vs . 16.4, Relative Risk 1.32; 95% Confidence Internal 1.05-1.67; p0.01) . This study calls the attention for the need of a more strict and determined educational program in order to provide mechanisms for an adequate administration of prophylactic antibiotics to patients submitted to high-risk surgeries.

Med Klin (Munich), 1998 Mar 15, 93(3), 165 - 9
{Quantitative cultures in diagnosis of pneumonia--a method for routine practice?}; Ewig S et al.; Quantitative cultures of respiratory secretions represent a valid technique for the diagnosis of ventilator-associated pneumonia . Contamination, colonization and true infection can be differentiated with a reasonable specificity using established cut-offs of bacterial colony counts . Quantitative investigations provide local epidemiological databases as a framework for empirical antimicrobial policies and may also prove helpful in the guidance of individual antimicrobial therapy . Another reasonable indication is HIV-associated pneumonia . However, the use of this technique in routine practice is hampered by the high expertise and experience that will be necessary to be successfully used . Nevertheless, in view of the need to identify bacterial susceptibility patterns, at least large treatment centers should routinely use this most powerful diagnostic technique.

Schweiz Rundsch Med Prax, 1998 Mar 18, 87(12), 403 - 12
{Sensitivity of bacteria to therapeutic drugs (Zurich 1996)}; Wust J et al.; This paper describes the frequency of susceptibility of Gram-negative and Gram-positive bacteria against antibacterial agents . The data are based on all susceptibility tests performed in 1996 at the Department of Medical Microbiology of the University of Zurich and at the private medical laboratory "medica" in Zurich . The evaluation of the results from 1975 to 1996 shows that susceptibilities against the antimicrobial agents tested have not changed markedly in this period with few exceptions . The tables may be a help for the physician in his decision for a "calculated chemotherapy" of bacterial infections.

Biochemistry, 1998 Mar 24, 37(12), 4288 - 98
Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin; Hwang PM et al.; The solution structure of bovine lactoferricin (LfcinB) has been determined using 2D 1H NMR spectroscopy . LfcinB is a 25-residue antimicrobial peptide released by pepsin cleavage of lactoferrin, an 80 kDa iron-binding glycoprotein with many immunologically important functions . The NMR structure of LfcinB reveals a somewhat distorted antiparallel beta-sheet . This contrasts with the X-ray structure of bovine lactoferrin, in which residues 1-13 (of LfcinB) form an alpha-helix . Hence, this region of lactoferricin B appears able to adopt a helical or sheetlike conformation, similar to what has been proposed for the amyloidogenic prion proteins and Alzheimer's beta-peptides . LfcinB has an extended hydrophobic surface comprised of residues Phe1, Cys3, Trp6, Trp8, Pro16, Ile18, and Cys20 . The side chains of these residues are well-defined in the NMR structure . Many hydrophilic and positively charged residues surround the hydrophobic surface, giving LfcinB an amphipathic character . LfcinB bears numerous similarities to a vast number of cationic peptides which exert their antimicrobial activities through membrane disruption . The structures of many of these peptides have been well characterized, and models of their membrane-permeabilizing mechanisms have been proposed . The NMR solution structure of LfcinB may be more relevant to membrane interaction than that suggested by the X-ray structure of intact lactoferrin . Based on the solution structure, it is now possible to propose potential mechanisms for the antimicrobial action of LfcinB.

Am J Vet Res, 1998 Apr, 59(4), 464 - 7
Clinical and microbiological effects of controlled-release local delivery of minocycline on periodontitis in dogs; Hayashi K et al.; OBJECTIVE: To evaluate the clinical and microbiological efficacy of minocycline in a subgingival local delivery system as an adjunct to tooth scaling and root planing in dogs with periodontal disease . ANIMALS: Nine 4- to 7-year-old Beagles with periodontitis . PROCEDURE: After scaling of teeth and root planing, 2 treatment and 1 or 2 control sites were selected for each dog: treated sites (n = 18) received minocycline hydrochloride periodontal formulation and control sites (n = 12) received ointment base (no minocycline) . Gingival crevicular fluid was collected at a baseline (prior to treatment) and at week 4 . Clinical and microbiological effects were evaluated and compared among sites . RESULTS: In minocycline-treated sites, clinical indices were significantly decreased at week 4, compared with those at baseline . Minocycline-treated sites were associated with a significant decrease in gingival crevicular fluid, probing depth, and bleeding on probing values, compared with those for control sites at week 4 . Compared with that for control sites, total bacteria count in periodontal pockets of minocycline-treated sites had an obvious tendency to decrease by week 4 . Proportions of Porphyromonas and Fusobacterium spp were significantly decreased at week 4, compared with proportions at control sites and with pretreatment (baseline) values . CONCLUSIONS: When used as an adjunct to tooth scaling and root planing, minocycline periodontal formulation stimulated favorable clinical and antimicrobial responses.

Curr Eye Res, 1998 Apr, 17(4), 348 - 62
Identification, origins and the diurnal role of the principal serine protease inhibitors in human tear fluid; Sathe S et al.; PURPOSE: Previous work identified polymorphonuclear leukocyte (PMN) elastase as the major caseinolytic entity in tears collected after overnight eye closure . This study was designed to identify the principal serine protease inhibitors (serpins) in tears and to determine their function in the regulation of PMN cell proteases on eye closure . METHODS: Reflex and closed eye tear samples were collected by microcapillary tube and centrifuged . After reflex and closed eye supernatants (R and C) were fractionated by HPLC, samples were subjected to casein zymography and reverse zymography . Western blots were utilized to screen tears and HPLC fractions for elastase, cathepsin G and proteinase-3 and to obtain semi-quantitative data on alpha 1-protease inhibitor (alp1), alpha 1-antichymotrypsin (alpha 1-Achy), secretory leukocyte protease inhibitor (SLPI), elafin and alpha 2-macroglobulin (alpha 2-M) as well as associated complexes and products . To confirm specificity of reactivity, samples were immunoprecipitated for a given protease or serpin and screened for the coprecipitation of interacting species . RESULTS: Although R fluid contains no caseinolytic activity, it contains low levels of serpin-like activity principally in the form of SLPI (5-10 ng/microliter) . Lesser amounts of alpha 2-M, alpha 1-Achy and alp1 (approximately < 1-3 ng/microliter) are also evident . C fluid is associated with very high levels of PMN cell proteases along with a approximately 5-20-fold increase in the concentrations of all of the above inhibitors . Trace levels of elafin were also detected . The concentrations of rapid reacting inhibitors exceeded that of proteases, with SLPI, alpha 1-Achy and alp1 being the principal functional entities . In atypical samples, complexes of elastase and alpha 2-M were also encountered . CONCLUSIONS: SLPI, a known antimicrobial agent and an elastase and cathepsin G inhibitor, is the principal serpin in R fluid . C fluid is associated with a marked increase in the concentrations of an array of rapid reacting serpins capable of inhibiting all known PMN cell serine proteases . In the normal closed eye, the concentration of rapid reacting inhibitors always exceeds that of proteases with C fluid also containing a functional reserve of the slow reacting inhibitor alpha 2-M.

Crit Care Clin, 1998 Apr, 14(2), 283 - 308
Antibiotic use in the critical care unit; Ambrose PG et al.; The antimicrobial management of patients in the critical care unit is complex . Not only must the clinician be familiar with a number of clinical, microbiological, pharmacological, and epidemiological observations but also fundamental pharmacodynamic concepts . It is an understanding of these concepts that forms the basis for the design of dosing strategies that maximize clinical efficacy and minimize toxicity . Antimicrobial selection is further complicated by the plethora of new antimicrobial agents available with varying clinical utility . Nowhere is this more evident than in the quinolone class of antibiotics . To aid the clinician in differentiating between quinolones it now seems reasonable to create a classification system akin to the generation grouping applied to the cephalosporins . Our classification is based upon the pharmacodynamic principles discussed within this article.

Inflammation, 1998 Apr, 22(2), 191 - 201
Azithromycin impact on neutrophil oxidative metabolism depends on exposure time; Levert H et al.; Several antimicrobial agents have already been investigated relating to their influence on neutrophil ROS generation . Azithromycin provides, a dose-related anti-oxidant effect, after 15 min incubation, with the stimulating agent FMLP, as well with PMA or S . aureus . This finding was however obtained with concentrations not considered in therapeutics . Since short incubation times are not representative of the physiological situation, and since azithromycin is characterized by prolonged high concentrations within phagocytes, the same experiments were performed over 2 and 4 h exposures . A time-dependent anti-oxidant effect was then reported . The maximum effect was obtained with PMA (IC50 were 856 and 30 micrograms/ml for 15 min and 4 h incubation times respectively) . Time-dependent modifications of neutrophil oxidative metabolism seem to be correlated with intracellular concentrations . Depressed oxidative metabolism might be related neither to azithromycin cellular toxicity, nor to superoxide scavenging properties . By increasing exposure periods, therapeutic concentrations could therefore lead to an anti-inflammatory effect, potentially of clinical interest since associated with bacteriostatic activity.

Crit Care Clin, 1998 Apr, 14(2), 263 - 82
Infections in nonleukopenic compromised hosts (diabetes mellitus, SLE, steroids, and asplenia) in critical care; Cunha BA; Acutely ill patients who are immunocompromised but not neutropenic most commonly are: (1) diabetic; (2) on chronic high-dose steroid therapy; (3) have lupus; or (4) have impaired or absent splenic function . These patients often present in the CCU because of the severity of their infection . Differential diagnosis may be approached by first considering the patient's underlying disease, i.e., SLE . The next step in the diagnostic process is to appreciate the immune defect associated with these disorders . The nature of the immune defect determines which clinical pathogens are related to the immune defect . Pathogens are associated with a sterotyped pattern of organ involvement . The object of the diagnostic analysis is to determine the most likely organism affecting a particular organ system, given the defect in host defenses associated with the patient's underlying illness . In this way, a useful clinical diagnosis can be made rapidly, and appropriate clinical specimens obtained for diagnostic testing . Often empiric therapy must be started pending the results of diagnostic testing . In such situations, empiric therapy ordinarily is directed against the bacterial pathogens most likely to cause disease relevant to the patient's impaired defenses . Specific therapy for unusual or exotic pathogens should not be empiric and should be based on demonstration of a pathogenic role by the microorganism . In the case of miliary tuberculosis or invasive fungal disease, a case may be made for early empiric therapy to cover these organisms if there is sufficient clinical suspicion based on the presenting signs and symptoms as well as the pattern of organ involvement . As with all infections, but particularly in immunocompromised patients, the early initiation of appropriate antimicrobial therapy is essential and often life-saving.

Crit Care Clin, 1998 Apr, 14(2), 199 - 219
Antibiotic resistance problems in the critical care unit; Mainardi JL et al.; The increased resistance of bacteria to antimicrobial agents poses major therapeutic problems for the treatment of patients hospitalized in critical care units . This article discusses the mechanisms of resistance and the basic rationale for the treatment of infected patients . The authors also discuss methods used to control the dissemination of resistant bacteria from patient to patient, the complex problems of colonization, and the strategies used to delay the emergence of resistance to new antibiotics.

J Chromatogr A, 1998 Mar 27, 800(2), 377 - 81
Novel quartz flow-cell as a post-column photochemical reactor for high-performance liquid chromatography; Tanaka M et al.; The construction of a new post-column photochemical reactor with quartz flow cells in series for high-performance liquid chromatography (HPLC) is described . The performance of the new reactor was compared with a conventional open tubular PTFE coil reactor . The sensitivity, accuracy and precision obtained with both reactors are comparable . The new reactor has the obvious advantages of smaller cell volume as well as inertness and resistance to not only light and heat produced by the UV lamp, but also to organic solvents in the mobile phases, which results in greatly improved durability, reduced peak broadening and shorter chromatographic run times . Application of the new reactor to the fluorescence detection of DU-6859a, a new fluoroquinolone antimicrobial agent, in human serum is reported.

Schweiz Med Wochenschr, 1998 Mar 14, 128(11), 393 - 9
{Complement and its role in immune response}; Hess C et al.; The complement system as a part of innate immunity is considered to provide rapid tough incomplete antimicrobial activity . However, besides providing a first-line defence, innate immunity plays additional important roles: it initiates and improves the slower, but more specific, acquired immune response . The recognition and destruction of noxious substances, as well as initiation of the acquired immune response, are accompanied by potentially hazardous inflammation . The inflammatory process has thus to be tightly regulated . In this overview, innate immunity and its interactions with acquired immunity are discussed with the main focus on the complement system . Our scientific interests are integrated into the discussion on complement.

J Hosp Infect, 1998 Mar, 38(3), 217 - 22
Molecular markers for the investigation of Mycobacterium gordonae epidemics; Vogiatzakis E et al.; Mycobacterium gordonae was isolated as a light growth from bronchoalveolar aspirates from nine patients over 12 months . All patients were in one hospital, and had been bronchoscoped for suspected malignancy . None of the patients had symptoms or radiographic findings of mycobacterial infection . The isolates were characterized by biochemical tests and molecular hybridization . Random amplified polymorphic DNA analysis (RAPD) was used to test whether the strains had a common origin . All the isolates generated four to eight fragments, and almost all presented distinct RAPD patterns . Antimicrobial resistance patterns to six agents confirmed that the isolates were unrelated . Thus epidemiologically unrelated strains of M . gordonae can exist as contaminants in the same department over a relatively short time frame . RAPD analysis is easy to perform, gives rapid results, and can be used for epidemiological analysis of M . gordonae isolates.

Infection, 1998 Mar-Apr, 26(2), 131 - 2
Brucella-infected ovarian dermoid cyst causing initial treatment failure in a patient with acute brucellosis; Uwaydah M et al.; A 37-year-old woman was diagnosed with acute brucellosis . Despite appropriate antimicrobial therapy, high fever persisted . A contrast enhanced CT scan of the abdomen and pelvis revealed a left ovarian dermoid cyst . On the first postoperative day after left ovariectomy and right ovarian cystectomy were performed, the patient defervesced abruptly and continued to be completely afebrile . Cultures from bone marrow and dermoid cyst grew Brucella melitensis . The observation of a Brucella-infected ovarian dermoid cyst, which has not been previously reported, illustrates the importance of localized brucellosis as a cause of persistent infection despite appropriate antimicrobial therapy.

Dent Today . 1997 Mar;16(3):48, 50.
Current dental chemotherapeutics, Part 2; Cianco SG; Periodontal diseases are the result of bacterial infections . Antimicrobial and other chemotherapeutic agents are effective adjuncts to mechanical therapy in helping practitioners limit the progression of disease . Topical antimicrobials used as mouthrinses can control supragingival plaque . Studies demonstrate that irrigation devices enhance the effectiveness of antimicrobials . Antibiotics have been shown to be of value in treating juvenile periodontitis, and rapidly advancing and refractory periodontitis . The use of tetracyclines to promote healing by stabilizing collagen and the use of nonsteroidal anti-inflammatory drugs and prostaglandin inhibitors offer promise for controlling periodontal disease.

Antimicrob Agents Chemother, 1998 Apr, 42(4), 911 - 5
Synthesis and antibacterial evaluation of novel water-soluble organic peroxides; Liu W et al.; A set of new water-soluble organic peroxides has been synthesized and evaluated for in vitro antibacterial activity as part of an effort to develop new antibacterial agents for the treatment of acne vulgaris . The water solubility of these new dialkyl peroxides and peroxyesters was achieved by incorporating either a quaternary ammonium group or a polyethylene glycol moiety . These peroxides are effective against both gram-positive and gram-negative bacteria and have a prolonged activity compared to that of benzoyl peroxide and other peroxide-type antiseptic agents . Among them 4-{{(tert-butylperoxy)carbonyl}benzyl}triethylammonium chloride and {10-(tert-butylperoxy)decyl}trimethylammonium bromide have the broadest antimicrobial spectrums . We have shown that the oxidizing properties of the dioxy group of these compounds are responsible for their antibacterial activities.

Antimicrob Agents Chemother, 1998 Apr, 42(4), 818 - 20
In vitro evaluation of drug susceptibilities of Babesia divergens isolates; Brasseur P et al.; The susceptibilities of three bovine and two human Babesia divergens isolates to antimicrobial agents were evaluated in vitro by a tritiated hypoxanthine incorporation assay . The MICs at which 50% of isolates are inhibited (MIC50s) for mefloquine (chlorhydrate), chloroquine (sulfate), quinine (chlorhydrate), clindamycin (phosphate), pentamidine (isethionate), phenamidine (isethionate) plus oxomemazine (chlorhydrate), lincomycin (chlorhydrate monohydrate), and imidocarb (dipropionate) were determined . Except for imidocarb, the MIC50s observed for the different isolates were close . Imidocarb and the combination of phenamidine plus oxomemazine exhibited the highest in vitro activity, while antimalarial agents such as mefloquine, choroquine, and quinine were inactive . Other drugs had intermediate activities . The data support further in vitro evaluation of antimicrobial agents active against B . divergens for the improvement of therapeutic strategies.

Photochem Photobiol, 1998 Apr, 67(4), 399 - 403
Fluoroquinolone antimicrobials: singlet oxygen, superoxide and phototoxicity; Martinez LJ et al.; The fluoroquinolone antibacterial agents possess photosensitizing properties that lead to phototoxic responses in both human and animal subjects . The phototoxicity order reported in humans is: fleroxacin > lomefloxacin, pefloxacin >> ciprofloxacin > enoxacin, norfloxacin and ofloxacin . Studies both in vivo and in vitro have related this phototoxicity to the generation of reactive oxygen species including hydrogen peroxide and the hydroxyl radical . We determined the quantum yields of singlet oxygen generation (phi delta) by detection of the singlet oxygen (1O2) luminescence at 1270 nm for several fluoroquinolones, naphthyridines and other structurally related compounds . All the fluoroquinolones examined have low phi delta values ranging from 0.06 to 0.09 in phosphate buffer at pD 7.5 . We also determined the 1O2 quenching constants for these compounds and their values were on the order of 10(6) M-1 s-1, except for lomefloxacin whose rate constant was 1.8 x 10(7) M-1 s-1 . The phi delta values were significantly decreased in a solvent of lower polarity such as methanol (0.007 < or = phi delta < or = 0.02) . The production of 1O2 by these antibiotics did not correlate with the order reported for their phototoxicity . We also measured the photogeneration (lambda > 300 nm) of superoxide by these antibacterials in dimethylsulfoxide using electron paramagnetic resonance and the spin trap 5,5-dimethyl-1-pyrroline N-oxide . Although there is not a one-to-one correspondence between the relative rates of superoxide generation and the phototoxicity ranking of the fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a faster rate . Nevertheless, the magnitudes of the observed differences do not appear sufficient to explain the range of fluoroquinolone phototoxicity potencies in human and animal subjects in general and the high activity of fleroxacin and lomefloxacin in particular . For these latter drugs the photoinduced loss of the F8 atom as fluoride and the concomitant generation of a highly reactive carbene at C-8 provide a more plausible mechanism for their potent phototoxic and photocarcinogenic properties.

Clin Biochem, 1998 Feb, 31(1), 1 - 14
Bioluminescence-based assays for detection and characterization of bacteria and chemicals in clinical laboratories; Billard P et al.; OBJECTIVES: To survey recent advances in the application of bioluminescence to public health problems . The usefulness of bacterial (lux) and eucaryotic (luc) luciferase genes is presented, along with several examples that demonstrate their value as "reporters" of many endpoints of clinical concern . CONCLUSIONS: The development of new technologies for monitoring biological and chemical contaminants is in continuous progress . Recent excitement in this area has come from the use of genes encoding enzymes for bioluminescence as reporter systems . Applications of the recombinant luciferase reporter phage concept now provide a sensitive approach for bacterial detection, their viability, and sensitivity to antimicrobial agents . Moreover, a number of fusions of the lux and luc genes to stress inducible genes in different bacteria can allow a real-time measurement of gene expression and determination of cellular viability, and also constitute a new tool to detect toxic chemicals and their bioavailability.

Am J Dermatopathol, 1998 Apr, 20(2), 185 - 8
Cutaneous malakoplakia in a patient with acquired immunodeficiency syndrome (AIDS); Barnard M et al.; Malakoplakia is an uncommon granulomatous lesion that afflicts predominantly immunocompromised individuals but is extremely rare in acquired immunodeficiency syndrome (AIDS) . We report a case of cutaneous malakoplakia in an AIDS patient that presented as a banal right axillary abscess which resolved after excision and drainage . The rarity of malakoplakia in AIDS may be due to a relative or selective preservation of antimicrobial function of monocytes . Malakoplakia is distinguished from other inflammatory or neoplastic lesions by the presence of Michaelis-Gutmann bodies . A correct diagnosis is usually made only after biopsy and is an indication to use antimicrobial agents with adequate cellular penetration and concentration.

Zentralbl Veterinarmed B, 1998 Mar, 45(2), 87 - 94
Identification and characterization of Arcobacter isolates from broilers by biochemical tests, antimicrobial resistance patterns and plasmid analysis; Harrass B et al.; A total of 89 Arcobacter butzleri isolates obtained from freshly slaughtered broilers was investigated for their biochemical capacities by using the API CAMPY system as well as additional growth and tolerance tests, for their antimicrobial resistance patterns and their plasmid content . Among these techniques, biochemical profiling and antimicrobial resistance testing proved to be the most discriminatory methods as confirmed by the calculation of discriminatory indices . These two methods might represent valuable tools for epidemiological analysis of A . butzleri isolates . Small plasmids of up to 5 kbp were detectable in only 21 of the 89 isolates while the remaining 68 A . butzleri isolates were plasmid-free.

Pediatr Rev, 1998 Apr, 19(4), 142 - 3
Nasal septal hematoma; Ginsburg CM; Nasal septal hematoma is a rare but potentially serious complication of nasal trauma . Proper management consists of early recognition, prompt surgical evacuation of the hematoma, and antimicrobial therapy if a secondary nasal septal abscess is suspected . Clindamycin is recommended as initial therapy until the results of cultures and susceptibility studies are available.

Pediatr Rev, 1998 Apr, 19(4), 118 - 27
Cephalosporins: an update; Prober CG; The cephalosporins are the largest and most diverse family of antimicrobial agents available . Although they rarely are considered drugs of first choice for the therapy of bacterial infections, they are the most commonly prescribed agents for both ambulatory and hospitalized patients . The first-generation agents have the most limited spectrum of bactericidal activity, but they are the most potent against Gram-positive microbes . The third- and fourth-generation agents have a broad spectrum of activity that includes the majority of Gram-negative pathogens . However, they are less active than their first-generation counterparts against Gram-positive bacteria, especially S aureus . The cephalosporins generally are well tolerated, and the oral agents are palatable . However, their use is limited by increasing resistance among certain groups of bacteria and high cost, especially of the parenteral and recently licensed oral agents . The prudent physician need not be familiar with all cephalosporins, but should be knowledgeable about a select few.

Vet Clin North Am Small Anim Pract, 1998 Mar, 28(2), 249 - 67
Treatment of endotoxic shock: glucocorticoids, lazaroids, nonsteroidals, others; Howe LM; Review of the literature would indicate that a therapy inhibiting a single step in the inflammatory mediator cascade, although potentially beneficial, cannot serve as the "magic bullet" in endotoxic shock . Thus, combination therapy using drugs that target multiple steps in the mediator cascade may prove useful in the future . Until controlled clinical studies have been performed in veterinary medicine using the agents discussed in this manuscript (or others), many questions will remain regarding the best possible pharmacologic therapies to use in supplementing traditional supportive care (e.g., fluids, broad-spectrum antimicrobials) measures . Many of the therapies discussed in this manuscript hold tremendous potential, but must be administered before endotoxic shock occurs or early in the course of endotoxic shock to elicit a beneficial response . Unfortunately this is not usually possible in the clinical situation . Further, the possibility of eliciting a detrimental response by use of drugs at inappropriate dosages or too late in the course of the disease must be considered . In time, therapies may be grouped into those that hold promise for being beneficial in the patient at risk for endotoxic shock and those that are beneficial for treatment of established endotoxic shock . Therapies that may hold promise for the patient with established endotoxic shock possibly include the lazaroids, certain NSAIDs, pentoxifylline, and selective inhibitors of iNOS activity . Although still controversial, methylprednisolone and other glucocorticoids are probably best reserved for the patient at risk for endotoxic shock, or those identified very early in the course of endotoxemia and endotoxic shock, and should never be used in conjunction with NSAIDs . Since no one therapy is likely to provide the "magic bullet" for the patient in endotoxic shock, treatment may ultimately involve combination therapy using some of these drugs that target different pathways and mediators and may also include antibodies against endotoxin or its mediators.

Vet Clin North Am Small Anim Pract, 1998 Mar, 28(2), 197 - 213
Principles of antimicrobial therapy; Whittem T et al.; It has been 2500 years since the Chinese began applying moldy soybean curd to cure skin infections . Technology today has refined the benefits of antibiotic-forming molds and bacteria and has greatly increased the number of antimicrobial drugs available to combat infection . Understanding the principles fundamental to rational therapy with these drugs will ensure the best of possible outcomes.

J Am Acad Dermatol, 1998 Apr, 38(4), 559 - 63
A randomized trial of acidified nitrite cream in the treatment of tinea pedis; Weller R et al.; BACKGROUND: Nitric oxide is continually released from normal skin and has antimicrobial effects . An acidified nitrite cream releases supraphysiologic concentrations of nitric oxide and is fungicidal in vitro . OBJECTIVE: The purpose of this study was to assess the efficacy of an acidified nitrite cream as treatment for tinea pedis . METHODS: Sixty patients were recruited with both a clinical diagnosis of tinea pedis and hyphae identified on direct microscopy; they were randomly placed into an active group treated with twice-daily application of a mixture of 3% salicylic acid in aqueous cream and 3% nitrite in aqueous cream for 4 weeks and a control group treated with 3% salicylic acid in aqueous cream and aqueous cream alone . Nineteen patients completed the trial in the active group and 16 patients in the control group . Mycologic cure (negative results on microscopy and culture) and clinical improvement were measured at 0, 2, and 4 weeks and after a 2-week interval with no treatment . RESULTS: At the end of the treatment period, 18 of the 19 patients in the active group were mycologically cured as were 11 of 16 in the control group (p = 0.042) . Two weeks after the cessation of treatment, 13 of 19 patients in the active group were mycologically cured and 5 of 16 in the control group (p = 0.028) . The initial clinical scores in the active and control groups were 8.1 and 8.19 (two-tailed p = 0.95) . At 4 weeks they were 1.66 and 6.0 (two-tailed p = 0.002) and after 2 weeks with no treatment 1.45 and 7.4 (two-tailed p < 0.0002) . CONCLUSION: Acidified nitrite is effective therapy for tinea pedis.

Free Radic Res, 1998 Jan, 28(1), 1 - 14
Phagomimetic action of antimicrobial agents; Gutteridge JM et al.; A wide variety of extracted and synthesised drug molecules have electron transfer capabilities which allow them to generate reactive oxygen species (ROS) . In particular, many antibiotics that kill or inhibit bacteria, yeasts and cancer cells readily transfer electrons to oxygen making superoxide and hydrogen peroxide in the process . When suitable redox active forms of iron are available, Fenton chemistry occurs generating the highly damaging hydroxyl radical . This type of chemistry is very similar to that which evolved within phagocytic cells as part of their microbial killing armoury . Many antibiotics, when used in model systems, have well defined pharmacological actions against key cellular functions, but their clinical usefulness is also often demonstrable at concentrations in vivo well below their in vitro minimum inhibitory concentrations . These observations have led us to propose that a common mechanism exists whereby phagocytic cells and antibiotics exploit the use of ROS for microbial killing.

Diagn Microbiol Infect Dis, 1998 Feb, 30(2), 83 - 7
The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy; Kozak SF et al.; The principal side effect of the antimycobacterial agent ethambutol (EMB) is an optic neuropathy with clinical features very similar to a mitochondrial hereditary optic neuropathy (Leber's) . The mechanism of EMB-induced optic neuropathy may be EMB's chelation of copper, thereby precluding normal cytochrome c oxidase activity and mitochondrial metabolism in the optic nerve . Before attempting to use therapeutic copper to replenish endogenous stores in an attempt to preclude EMB-induced optic neuropathy, we wished to determine whether EMB is still effective against mycobacteria in the presence of copper . EMB and copper, alone and in combination, were tested against six strains of Mycobacterium tuberculosis and five strains of Mycobacterium avium using a radiometric broth macrodilution assay . Copper did not effect EMB's antimicrobial actions against either species of mycobacteria . This in vitro study suggests that if copper were given to patients to prevent EMB-induced optic neuropathy, it would not compromise EMB's bacteriostatic properties.

Ned Tijdschr Geneeskd, 1997 Dec 6, 141(49), 2392 - 6
{Current antimicrobial drugs}; van Kasteren ME et al.; In the past few years several new antibiotics became available, but no major inventions as to new treatment strategies were made . There are a few new broad-spectrum antibiotics for the intravenous route like piperacillin-tazobactam, the carbapenem meropenem and the fourth-generation cephalosporins . cefepime and cefpirome . New oral antibiotics include the third-generation cephalosporins ceftibuten, cefetamet and cefpodoxime and the macrolides clarithromycin and azithromycin . The last two have the great advantage of less frequent dosing and fewer side effects than erythromycin . Of the two new quinolones, sparfloxacin and trovafloxacin, trovafloxacin is the more promising . In the treatment of Gram-positive infections the glycopeptide teicoplanin became available and the combined derivatives quinupristin-dalfopristin may prove valuable in the future.

Adv Parasitol, 1998, 40, 5 - 36
Natural history and biology of Cryptosporidium parvum; Tzipori S et al.; The taxonomy of the genus Cryptosporidium remains ambiguous, because the current criteria for speciation are insufficient to validate the 6-8 named species . Cross-transmission experiments have shown varying and conflicting results, and the limited genetic data available do not necessarily support currently proposed species designations . The reasons for this ambiguity lie with the ubiquitous nature of Cryptosporidium, probably infecting all vertebrates and variety of tissues therein, and the absence of reference strains with defined virulence attributes that can be linked to genetic markers for comparative analysis . The inability to classify oocysts or confidently to identify their origin, implicate oocysts from all sources as hazardous to humans . Another major issue is the unusual degree of resistance that Cryptosporidium has shown to antiprotozoan and antimicrobial agents . The intracellular but extracytoplasmic domain the parasite occupies is in itself a significant barrier to drug entry . In support of this we outline how the intracellular niche of this parasite differs from the related Apicomplexans, Plasmodium and Toxoplasma, and delineate why the feeder organelle membrane, rather than, or in addition to, the parasitophorous membrane, is the major portal of nutrient entry for Cryptosporidium . The broad conclusion is that anticryptosporidial agents will have to enter the parasite via the multiple apical membranes that camouflage the parasite, or via the host cell, possibly transported by vesicles to the feeder organelle membrane . This may have major implications for rational drug discovery and design.

Clin Oral Investig, 1997 Feb, 1(1), 5 - 11
Biological aspects of root canal filling materials--histocompatibility,cytotoxicity, and mutagenicity; Geurtsen W et al.; In order to minimize the incidence of local and/or systemic side effects, the biocompatibility of all endodontic materials should be investigated by various in vitro and in vivo tests prior to clinical application . The battery of in vitro tests includes determinations of mutagenicity, cytotoxicity, and antibacterial effects . Several reports have shown that paraformaldehyde-containing ZnO-eugenol cements in particular, such as Endomethasone and N2, are antibacterial . On the other hand, it has been found that endodontic materials with strong antimicrobial activity are frequently mutagenic, i.e., primarily those which release formaldehyde . Cell culture tests clearly show significantly different cytocompatibility of the various types of endodontic sealers: in general, formaldehyde-containing ZnO-eugenol cements are classified as highly/extremely cytotoxic, whereas most Ca(OH)2-based sealers are rated as possessing good or excellent cytocompatibility . These results were confirmed by numerous histological studies in vivo . Sealers with inferior biocompatibility, such as formaldehyde-releasing materials, should no longer be applied in practice because safer alternatives are available.

Int J Antimicrob Agents, 1997 Jan, 9(3), 201 - 5
Antibiotic resistance in Escherichia coli isolated from blood and cerebrospinal fluid: a 6-year study of isolates from patients in England and Wales; Threlfall EJ et al.; A study of the incidence of resistance to antimicrobial drugs in Escherichia coli from blood and CSF made in England and Wales in the 6-year period 1991 1996 has demonstrated a significant increase in the incidence of strains resistant to ampicillin and ciprofloxacin, two antibiotics used for first-line therapy of invasive disease . In particular, there has been a dramatic change in the occurrence of isolates with low level or high level resistance to ciprofloxacin; over 90% of isolates in the high level group were also resistant to at least four other antimicrobials . Physicians in England and Wales should be aware that there is now an increasing possibility of treatment failures when ciprofloxacin is used for the treatment of invasive E . coli infections.

Pharm Dev Technol, 1997 Nov, 2(4), 323 - 34
Microencapsulation of antimicrobial ceftiofur drugs; Bodmeier R et al.; Polymeric microparticles containing two ceftiofur salts as antimicrobial agents for intramammary application in dry cows were prepared by modified o/w-solvent evaporation methods (dispersion or cosolvent method) or by a w/o/w-multiple emulsion solvent evaporation method . The microspheres were characterized with respect to drug loading, drug release, and morphological properties . The three methods resulted in high encapsulation efficiencies . The choice of organic solvent/solvent mixture strongly affected the structure of the microparticles; both matrix and reservoir-type structures with different porosities were obtained . Scaling up to larger batch sizes resulted in microspheres with a faster drug release . The addition of water-miscible cosolvents to the water-immiscible polymer solution allowed the preparation of microparticles from a drug solution rather than a drug dispersion . Microparticles prepared by the cosolvent method could be separated after shorter time intervals from the aqueous phase; the microspheres had a denser matrix with finely dispersed drug crystals and a slower drug release when compared with microspheres prepared by the dispersion method, which had a more porous structure with larger embedded drug crystals . The cosolvent and dispersion methods present a simple alternative to the w/o/w-solvent evaporation method for the encapsulation of water-soluble drugs with an external water phase.

Ned Tijdschr Geneeskd, 1997 Nov 22, 141(47), 2297 - 301
{Favorable results with intravenous antimicrobial therapy outside the hospital}; van den Broek PJ et al.; OBJECTIVE: To determine whether intravenous home treatment with antimicrobial drugs of patients with an infection is feasible . DESIGN: Descriptive . SETTING: Academic Hospital, Leiden, the Netherlands . METHODS: In October 1992 a programme for intravenous home treatment of patients with infectious diseases was started . The programme was based on self-administration of the intravenous antibiotic therapy by the patient . The hospital pharmacy provided the antibiotics and infusion devices, an infectious diseases specialist supervised the home treatment and the nursing staff of the First Aid Department was available to change infusion cannulas . After assessment of their medical and psychosocial fitness in which the general practitioner was involved, thorough instruction on use of the infusion device and care of the infusion cannula, patients were sent home . RESULTS: In the period October 1992-September 1996, 162 patients (median age: 45.0 years (range: 3-82)) were treated at home for a median period of 15 days (1-221) . Osteomyelitis, arthritis, Lyme disease, septicaemia with secondary foci, and herpes virus infections were the most frequent indications for home treatment . Penicillins and cephalosporins were given in 70% of the cases, teicoplanin and antiviral drugs in 12% and 14%, respectively . For intermittent administration bolus injection, a mechanical or elastomeric pump were used, for continuous infusion a syringe or cassette pump . The intention of the programme that the patient performed the home treatment as much as possible without extra professional help, was realised in 82% of the patients . In 60% of the cases the patients were fully self supporting, in 22% family or friends played an important role . CONCLUSION: Home treatment with antimicrobial drugs intravenously is quite feasible . If this were fully implemented, about 1400 patients in the Netherlands could be treated in this manner.

Farmaco, 1997 Nov, 52(11), 679 - 83
Synthesis and antimicrobial activity of some new derivatives of 6,12-dihydroindolo{2,1-b}quinazolin-6,12-dione; Grandolini G et al.; Some derivatives of tryptantrine were prepared in order either to increase solubility and to study structure-activity relationship . All synthesized compounds were tested for antimicrobial activity.

Nippon Rinsho, 1998 Mar, 56(3), 752 - 61
{Drug delivery system for infectious diseases}; Maesaki S et al.; Various types of antimicrobial agents have been evolved to inhibit growth of or to kill different microorganisms . In recent years, encapsulation of antimicrobial agents in lipid formulations has been a popular practice in research work related to drug delivery system, although most of the studies are based primary on animal models . The recent developments of lipid formulations of anti-infectious drug (antibiotics, antifungals, and antiviral agents) with longer half-life opens new therapeutic avenues in treating infections . The passive targeting of liposomes to the sites of infection is of great value with respect to clinical application . Liposome entrapment can exchange their pharmacokinetics and, hence reduce their toxicity.

Arch Biochem Biophys, 1998 Mar 15, 351(2), 243 - 9
Characterization of two cDNA clones which encode O-methyltransferases for the methylation of both flavonoid and phenylpropanoid compounds; Gauthier A et al.; Enzymatic O-methylation of phenylpropanoid and flavonoid compounds is believed to be catalyzed by distinct classes of O-methyltransferases {EC 2.1.1.6x} . The O-methylated derivatives of phenylpropanoids and flavonoids play an important role in lignification and as antimicrobial compounds, respectively . Two cDNA clones, OMT1 and OMT2, which differ in three amino acid residues were isolated and characterized from the semiaquatic freshwater weed Chrysosplenium americanum (Saxifragaceae) . These two novel cDNA clones encode enzymes which catalyze the 3'-O-methylation of the flavonoid aglycones luteolin and quercetin, although they also catalyze the efficient 3/5-O-methylation of the phenylpropanoids caffeic and 5-hydroxyferulic acids, respectively . Both recombinant proteins were partially purified from an Escherichia coli expression system and their kinetic parameters were compared using two flavonoids and two phenylpropanoids as substrates . Although both gene products methylate caffeic acid and 5-hydroxyferulic acid to a similar extent, they exhibit a threefold higher affinity for and a four- to sixfold increase in turnover of flavonoid compounds . The gene product of OMT1 accepts the flavonoid substrates luteolin and quercetin for methylation at a higher rate than that of OMT2, as indicated by a two- to threefold increase in its Vmax values and turnover ratios . The fact that C . americanum accumulates a variety of highly methylated flavonols and exhibits little lignification suggests that these two flavonoid OMT clones have retained their ability to O-methylate phenylpropanoids as well . These results are discussed in relation to differences in the amino acid sequences of these two clones, as well as with other O-methyltransferases, and the evolutionary divergence of these genes in plants .

Int Endod J, 1997 Sep, 30(5), 297 - 306
Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis; Sjogren U et al.; This study investigated the role of infection on the prognosis of endodontic therapy by following-up teeth that had had their canals cleaned and obturated during a single appointment . The root canals of 55 single-rooted teeth with apical periodontitis were thoroughly instrumented and irrigated with sodium hypochlorite solution . Using advanced anaerobic bacteriological techniques, post-instrumentation samples were taken and the teeth were then root-filled during the same appointment . All teeth were initially infected; after instrumentation low numbers of bacteria were detected in 22 of 55 root canals . Periapical healing was followed-up for 5 years . Complete periapical healing occurred in 94% of cases that yielded a negative culture . Where the samples were positive prior to root filling, the success rate of treatment was just 68%--a statistically significant difference . Further investigation of three failures revealed the presence of Actinomyces species in each case; no other specific bacteria were implicated in failure cases . These findings emphasize the importance of completely eliminating bacteria from the root canal system before obturation . This objective cannot be reliably achieved in a one-visit treatment because it is not possible to eradicate all infection from the root canal without the support of an inter-appointment antimicrobial dressing.

J Nat Prod, 1998 Feb, 61(2), 306 - 8
Trichoflectin, a bioactive azaphilone from the ascomycete Trichopezizella nidulus; Thines E et al.; Trichoflectin (1), a new azaphilone belonging to the deflectin series, 6-deoxy-7-0-demethyl-3,4-anhydrofusarubin (2), and 6-deoxy-3,4-anhydrofusarubin (3) were isolated from submerged cultures of the ascomycete Trichopezizella nidulus . All compounds showed antimicrobial activity and inhibited dihydroxynaphthalene melanin biosynthesis in fungi . The structure of trichoflectin (1) was elucidated by spectroscopic methods.

Bioorg Med Chem, 1998 Feb, 6(2), 209 - 21
Transferred nuclear Overhauser effect study of macrolide-ribosome interactions: correlation between antibiotic activities and bound conformations; Bertho G et al.; The study of macrolide-ribosome interactions has been investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY) . A new medically important macrolide antibiotic, roxithromycin, with the replacement of the 9-keto group in erythromycin by a 9-oxime chain, was studied in the complex state with the bacterial ribosome . Analysis of transferred nuclear Overhauser effect (TRNOE) experiment resulted in a set of constraints for all protons pairs . These constraints were used in structure determination procedures based on molecular modelling to obtain a bound structure compatible with the experimental NMR data . The results compared with the conformational analysis of the substrate in solution indicate that only one specific conformation is preferred in the bound state while in the free state the sugar ring moities were relatively disordered . The bioactive macrolide antibiotics studied roxithromycin and erythromycin which displayed a strong NMR response, are metabolized in RU39001 and erythralosamine respectively which do not retain antimicrobial activity . The inactive major metabolites were used to define if TRNOEs observation may be characteristic of a biological activity . These control experiments gave essentially blank TRNOESY spectra . This study shows that Mg2+ does not play a direct role for the low affinity binding site studied by TRNOE what is in agreement with an hypothesis of two distinct binding levels, with a low affinity binding level necessary for the tight binding one.

Nippon Geka Gakkai Zasshi, 1998 Jan, 99(1), 40 - 5
{Immediate burn wound excision and grafting decreases the mortality rate and hospital stay duration in extensive burn patients}; Nakazawa H et al.; The treatment of patients with extensive burn injuries has begun to changed in recent years . Traditional methods have consisted of dressing the burn wound with topical antimicrobials, tubbing the patient daily, encouraging the shoughing off of eschar using surgical debridement as necessary, and finally, closing the granulating wound with split-thickness skin grafts after 2 to 4 weeks . An alternative and more radical procedure is now being used with increasing frequency: complete surgical excision of the eschar is performed as soon as the patient is hemodynamically stable after resuscitation from burn shock . From 1991 to 1997, we performed immediate burn wound excision and grafting in 15 extensive burn patients within 24 hours after injuries . The mean burn surface area (BSA) was 48 +/- 20%, and the mean burn index was 44 +/- 19 . The mean prognostic burn index (PBI = burn index + age) was 94 +/- 23 . There were 5 deaths, for an overall mortality rare of 33%, which is less than that experienced by 11 other burn units in Tokyo (51.4%) . The duration of hospital stay of survivors was approximately 1 day/%BSA.

Kekkaku, 1998 Feb, 73(2), 77 - 82
{Nontuberculous mycobacteriosis; the present status and in the future . 3--(1) . The view of development of new drugs against nontuberculous mycobacterial infections}; Kawahara S et al.; It is obvious that the number of patients with pulmonary nontuberculous mycobacterial infections is increasing gradually in Japan . Of these infections, M . avium complex (MAC) is the most common cause, and is known to be resistant to many antimicrobial drugs . At present, no standard regimen which is able to control MAC infections completely is established . For these reasons, the development of new drugs with strong antimycobacterial activity which are not cross-resistant to conventional antimycobacterial drugs is urgently desired . Thus, we studied in vitro activities of various drugs which are expected to be a new promising drug against nontuberculous mycobacterial infections, and reviewed clinical impact of these drugs . 1) New quinolones New quinolones including ofloxacin, ciprofloxacin, levofloxacin and sparfloxacin (SPFX), are considered to be active against M . tuberculosis, M . kansasii, M . fortuitum, but are inactive against MAC, M . chelonae, M . abscessus, M . scrofulaceum . Both AM-1155 and Du-6859a, newer quinolones, seemed to be comparable to or more active than SPFX which is considered to be most active now . 2) New macrolides Clarithromycin (CAM) has in vitro activities against various nontuberculous mycobacteria including MAC, and also has proven to have clinical potential not only for disseminated MAC infections in AIDS but also for pulmonary MAC infections . Therefore, CAM seems to be a candidate for one of the key drugs in the treatment of MAC infections . 3)Rifamycins Rifabutin (RBT) and rifapentine exhibited more potent in vitro and in vivo antimycobacterial activities than rifampicin . RBT has already demonstrated clinical effect against intractable tuberculosis and MAC infections . Thus, RBT is recommended for the prophylaxis of M . tuberculosis and MAC infections in AIDS patients in US . KRM-1648 displayed much more potent in vitro and in vivo activities than rifampicin against both M . tuberculosis and MAC . It is needed an effort to confirm its therapeutic efficacies . Now clinical phase study is going on in US . 4) Phenazines Clofazimine (CFZ), an effective antileprosy drug, is known to be active in vitro against various mycobacteria including MAC, and often used as a component of combination chemotherapy for disseminated MAC infections in AIDS patients in US . Recently, CFZ new analogs have been developed, and it is necessary to evaluate its activities against nontuberculous mycobacteria.

Kekkaku, 1998 Feb, 73(2), 71 - 6
{Nontuberculous mycobacteriosis; the present status and in the future . Mechanisms of host resistance to Mycobacterium avium complex and Mycobacterium tuberculosis infection}; Tomioka H et al.; In order to know profiles of the antimicrobial action of some microbicidal effector molecules against Mycobacterium avium complex (MAC) and M . tuberculosis (MTB), profiles of collaborating effects among reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) were studied, RNI and FFA exerted synergistic effects in killing MAC and MTB, while the combination of ROI (H2O2-mediated halogenation system) with FFA conversely caused antagonism . The combination of RNI with ROI displayed additive effects in killing MTB, whereas the same combination showed antagonistic effects against MAC . Murine peritoneal macrophages (M phi s) produced and/or released these three antimicrobial effectors in the order ROI, FFA, and RNI in response to cellular stimulation induced by their contact with MAC or MTB organisms . These findings indicate that the collaborating effect of RNI with FFA is crucial for M phi-mediated intracellular killing of MAC and MTB . Secondly, we examined the modes of bacterial growth of MAC and MTB in murine peritoneal M phi s and A-549 type II alveolar epithelial cell line . The growth rate of these organisms was much larger in A-549 cells than in M phi s . In addition, the growth rate of high-virulence MAC (N-260 strain) was significantly larger than that of low-virulence MAC (N-444 strain), when they were residing in M phi or A-549 cells . Although a high virulence MTB (strain Kurono) also showed much more rapid growth in M phi s than did low-virulence MTB (strain H37Ra), such a phenomenon was not observed for their intracellular growth in A-549 cells . MTB exhibited strong cytotoxic effects against M phi s but not against A-549 cells when resided in these cells . On the other hand, MAC organisms did not cause cytotoxicity even in M phi s . Although MAC and MTB infections caused significant increase in RNI production by M phi s but not by A-549 cells, there was no significant relationship between the degree of M phi RNI production by a given mycobacterial organism and its virulence . These findings indicate some important roles of type II alveolar epithelial cells as a target cell for primary invasion and transient growth of mycobacterial organisms in the host lungs.

Chem Biol, 1998 Mar, 5(3), 147 - 54
Solution structure of a synthetic lytic peptide: the perforin amino terminus; Natarajan K et al.; BACKGROUND: Killer lymphocytes secrete perforin, a 67 kDa protein that initiates T-cell cytolysis following aggregation and pore formation in target membranes . The resulting pores cause a breakdown of the transmembrane osmotic gradient and allow other cytolytic mediators to enter the target cell and initiate apoptosis . The cytolytic domain resides within the first 34 residues of the amino terminus of perforin, with residues 1-19 being sufficient for cytolytic activity . RESULTS: The solution structure of a 22-residue synthetic peptide (P22), corresponding to the amino terminus of human perforin, has been determined using high resolution nuclear magnetic resonance spectroscopy in the presence and absence of perdeuterated detergent (SDS) micelles . In aqueous solution, P22 exists mainly in a random conformation . However, it adopts a hook-like structure at the carboxyl terminus in the presence of SDS micelles when the positively charged residues cluster to form a turn that provides a binding surface to the negatively charged sulfate headgroups . CONCLUSIONS: The strong electrostatic interaction between the cationic region of the P22 peptide and the lipid headgroups probably weakens the membrane, facilitating insertion of the relatively neutral/hydrophobic stretch of P22, and is representative of the initial step of the lytic pathway . The structural model described here is probably relevant to understanding the mechanisms of other cationic antimicrobial peptides.

EMBO J, 1998 Aug 10, 17(5), 1217 - 27
A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway; Ferrandon D et al.; A hallmark of the systemic antimicrobial response of Drosophila is the synthesis by the fat body of several antimicrobial peptides which are released into the hemolymph in response to a septic injury . One of these peptides, drosomycin, is active primarily against fungi . Using a drosomycin-green fluorescent protein (GFP) reporter gene, we now show that in addition to the fat body, a variety of epithelial tissues that are in direct contact with the external environment, including those of the respiratory, digestive and reproductive tracts, can express the antifungal peptide, suggesting a local response to infections affecting these barrier tissues . As is the case for vertebrate epithelia, insect epithelia appear to be more than passive physical barriers and are likely to constitute an active component of innate immunity . We also show that, in contrast to the systemic antifungal response, this local immune response is independent of the Toll pathway.

J Antibiot (Tokyo), 1998 Feb, 51(2), 145 - 52
New quinolone compounds from Pseudonocardia sp . with selective and potent anti-Helicobacter pylori activity: taxonomy of producing strain, fermentation, isolation, structural elucidation and biological activities; Dekker KA et al.; Eight novel quinolones with anti-Helicobacter pylori activity were isolated from the actinomycete Pseudonocardia sp . CL38489 . The quinolones were very potent against H . pylori with MICs up to 0.1 ng/ml . The quinolones appear to be specific for H . pylori, since they did not show antimicrobial activity when tested against a panel of other microorganisms.

J Antibiot (Tokyo), 1998 Feb, 51(2), 123 - 9
Cremimycin, a novel 19-membered macrocyclic lactam antibiotic, from Streptomyces sp; Igarashi M et al.; A novel 19-membered macrocyclic lactam antibiotic, cremimycin, was isolated from the culture broth of an actinomycete strain . The producing organism, designated MJ635-86F5, was identified as a member of Streptomyces . Cremimycin was isolated from the mycelial cake by extraction with CHCl3-MeOH and precipitation with hexane-MeOH . The structure of cremimycin was determined by spectroscopic study . Cremimycin showed broad antimicrobial activities against Gram-positive bacteria including MRSA.

J Antibiot (Tokyo), 1998 Feb, 51(2), 112 - 6
CJ-12,373, a novel topoisomerase II inhibitor: fermentation, isolation, structure elucidation and biological activities; Inagaki T et al.; A novel isochroman carboxylic acid CJ-12,373 was isolated from Penicillium sp . CL22557 . CJ-12,373 inhibits both DNA gyrase-mediated supercoiling and relaxation without the formation of a cleavage intermediate, suggesting that CJ-12,373 inhibits DNA gyrase at a stage distinct from the religation step . CJ-12,373 is not selective for procaryotic DNA gyrase as it also inhibits relaxation mediated by eukaryotic topoisomerase II . The antimicrobial potency of CJ-12,373, however, is largely attributed to its inhibition of DNA gyrase.

J Med Chem, 1998 Mar 26, 41(7), 1014 - 26
Cytotoxic activities of Mannich bases of chalcones and related compounds; Dimmock JR et al.; Various Mannich bases of chalcones and related compounds displayed significant cytotoxicity toward murine P388 and L1210 leukemia cells as well as a number of human tumor cell lines . The most promising lead molecule was 21 that had the highest activity toward L1210 and human tumor cells . In addition, 21 exerted preferential toxicity to human tumor lines compared to transformed human T-lymphocytes . Other compounds of interest were 38, with a huge differential in cytotoxicity between P388 and L1210 cells, and 42, with a high therapeutic index when cytotoxicity to P388 cells and Molt 4/C8 T-lymphocytes were compared . In general, the Mannich bases were more cytotoxic than the corresponding chalcones toward L1210 but not P388 cells . A ClusCor analysis of the data obtained from the in vitro human tumor screen revealed that the mode of action of certain groups of compounds was similar . For some groups of compounds, cytotoxicity was correlated with the sigma, pi, or molar refractivity constants in the aryl ring attached to the olefinic group . In addition, the IC50 values in all three screens correlated with the redox potentials of a number of Mannich bases . X-ray crystallography and molecular modeling of representative compounds revealed various structural features which were considered to contribute to cytotoxicity . While a representative compound 15 was stable and unreactive toward glutathione (GSH) in buffer, the Mannich bases 15, 18, and 21 reacted with GSH in the presence of the pi isozyme of glutathione S-transferase, suggesting that thiol alkylation may be one mechanism by which cytotoxicity was exerted in vitro . Representative compounds were shown to be nonmutagenic in an intrachromosomal recombination assay in yeast, devoid of antimicrobial properties and possessing anticonvulsant and neurotoxic properties . Thus Mannich bases of chalcones represent a new group of cytotoxic agents of which 21 in particular serves as an useful prototypic molecule.

Farmaco, 1998 Jan, 53(1), 41 - 8
Stereoisomeric effect on antimicrobial activity of a series of quaternary ammonium salts; Gregan F et al.; Two homologous series of diastereoisomeric racemic +/- cis and +/- trans-N,N-dimethyl-N-alkyl-2-benzoyloxycyclohexylmethylammonium bromides with the number of carbon atoms in the alkyl chain from six to twenty (m = 6,8 .. . 20) were synthesised . Their structures have been elucidated by IR, UV and in some cases also with 1H and 13C NMR spectrometry . The title compounds were assayed for their antimicrobial activity on microorganisms S . aureus, E . coli and C . albicans . The highest antimicrobial activity was observed against S . aureus (log 1/MIC = 5.5 mol-1 dm3) and the lowest against E . coli (log 1/MIC = 4.5 mol-1 dm3) . The +/- cis and +/- trans stereoisomers of all eight couples of diastereoisomeric compounds show differences in their physico-chemical characteristics (including partition coefficient and lipophilicity) which is also reflected in the different antimicrobial activity of these diastereoisomers.

Semin Respir Infect, 1998 Mar, 13(1), 24 - 35
What new antibiotics to offer in the outpatient setting; Fraser KL et al.; The treatment of community-acquired pneumonia is empiric . Guidelines have been developed to assist the clinician in selecting antibiotics to cover the likely pathogens . Given the difficulty of predicting an etiologic agent from patient characteristics, radiologic findings, and laboratory studies, initial regimens recommend broad-spectrum coverage . In some circumstances, two antibiotics may be required . The prevalence of resistant organisms is increasing and must be considered when prescribing treatment . Patient compliance is essential for successful therapy but diminishes with inconvenient dosing schedules and with poorly tolerated medicines . A number of novel antimicrobials have either been just launched or are in the late stages of development . Most have been developed in an attempt to address the above concerns . This article focuses on the new oral cephalosporins, macrolides, and fluoroquinolones, and discusses the place of each in the therapy of community-acquired pneumonia.

Pharm Acta Helv, 1998 Jan, 72(5), 285 - 90
Synthesis of some 3-arylamino-5-aryloxymethyl{1,2,4}triazole derivatives and their antimicrobial activity; Demirayak S et al.; In this study, some 3-arylamino-5-aryloxymethyl{1,2,4}triazole derivatives were synthesized by reacting S-methyl-N'-arylisothiouronium iodide and 2-(aryloxy)alkanoic acid hydrazide . The structural elucidation of the compounds was performed by IR, 1H-NMR and MS spectroscopic data and elemental analyses results . Antibacterial and antifungal activities of the compounds were examined.

Dig Dis Sci, 1998 Mar, 43(3), 464 - 7
One-week triple therapy with lansoprazole, clarithromycin, and metronidazole to cure Helicobacter pylori infection in peptic ulcer disease in Korea; Perng CL et al.; The efficacy and acceptability of classical bismuth triple therapy may be limited by poor patient compliance and adverse effects . It is widely agreed that improved, simpler, and reliable therapies are needed to cure Helicobacter pylori infection and foster patient compliance . We evaluated the efficacy and side effects of a Bazzoli triple therapy substituting lansoprazole for omeprazole for H . pylori infection in active peptic ulcer in Korea (30 mg of lansoprazole, 250 mg of clarithromycin, and 400 mg of metronidazole, all twice daily) . H . pylori status was evaluated by rapid urease test, histology, and culture at entry and four or more weeks after ending antimicrobial therapy . Fifty-eight patients (mean age: 43 years) with gastric (N = 30) or duodenal ulcer (N = 28) and H . pylori infection were studied . H . pylori was cured in 47 (81%, 95% CI = 69-90%) . Mild side effects, including vomiting, diarrhea, and itching, were observed in four patients (7%) . Compliance averaged 95% . Fifty-five ulcers (95%) were healed . Pretreatment pylorobulbar deformity was observed in 49 patients (85%), and in 43 (88%) the deformity disappeared after treatment . Pretreatment metronidazole and clarithromycin resistance was observed in 87% and 2% of patients, respectively . The cure rate of H . pylori infection was significantly higher in patients >50 years of age than those <50 . Treatment with low-dose one-week lansoprazole, clarithromycin, and metronidazole resulted in a relatively low cure rate, but was well tolerated . Studies to define the optimal duration, dose, and dosing interval of this combination therapy in Korea are needed.

Trop Med Int Health, 1998 Feb, 3(2), 116 - 23
Patterns of antimicrobial use and antimicrobial resistance among healthy children in Bolivia; Bartoloni A et al.; OBJECTIVE: To determine the incidence of antimicrobial-resistant, nonpathogenic Escherichia coli among healthy children aged 6-72 months in Camiri town and a rural village, Javillo, in south-eastern Bolivia . METHOD: A community-based survey: stool samples were obtained from 296 healthy children selected by modified cluster sampling in Camiri and all 25 eligible children in Javillo . E . coli isolates were tested for antimicrobial susceptibility according to the standard disc diffusion method . By a questionnaire survey of 12 pharmacies and by using simulated patients, we investigated the antimicrobial availability and the usage patterns in Camiri town . RESULTS: In Camiri, over 90%, and in Javillo over 70% of children carried E . coli resistant to ampicillin, trimethoprim-sulphamethoxazole (TMP/SMX) or tetracycline . Overall, 63% of children carried E . coli with multiple resistance to ampicillin, TMP/SMX, tetracycline and chloramphenicol . In the simulated patients study, antimicrobials were dispensed inappropriately for 92% of adults and 40% of children with watery diarrhoea, and were under-prescribed for males with urethral discharge (67%) or females with fever and dysuria (58%) . The dose and/or duration of antimicrobials dispensed was almost always too low . CONCLUSION: Our study showed a disturbingly high prevalence of carriage of nonpathogenic E . coli resistant to antimicrobials . The prevalence of resistance to ampicillin and TMP/SMX was higher than that previously reported in developing countries . The existence of a large reservoir of resistance genes in healthy individuals in developing countries represents a threat to the success of antimicrobial therapy throughout the world . Programmes to improve rational and effective drug use in developing countries are urgently needed.

Br J Ophthalmol, 1998 Jan, 82(1), 29 - 34
Intrascleral dissemination of infectious scleritis following pterygium excision; Hsiao CH et al.; AIMS: To assess the clinical pictures, possible pathogenesis, management, and therapy of patients with infectious scleritis associated with multifocal scleral abscesses following pterygium excision . METHODS: The records of patients with infectious scleritis after pterygium excision who developed multifocal scleral abscesses presenting from 1988 to the end of 1995 were reviewed . Early culture of abscesses was performed, and topical, systemic antimicrobials, or both were given to all patients . Fourteen eyes were operated on in addition to antimicrobial treatment . RESULTS: The initial culture reports of scleral ulcers identified Pseudomonas species in 12 of these 18 patients, Aspergillus in one, Mycobacterium fortuitum in one, and mixed organisms in four . Subsequent abscess cultures were taken from 15 of the infected eyes, and revealed the same organism as the initial culture in 12 . Associated complications included four serous retinal detachments, three choroidal detachments, two double detachments, five complicated cataracts, and four recurrences of the initial infection . Four eyes required eventual enucleation and 11 eyes regained useful vision . CONCLUSIONS: With subsequent abscess cultures proving to be the same organism as found in the initial ulcer, the abscess formation appears to represent intrascleral dissemination . Early diagnosis and appropriate, prolonged topical plus systemic antimicrobial treatment are essential to halt the progression of such severe infections.

J Pharm Biomed Anal, 1998 Jan, 16(5), 723 - 32
Nuclear magnetic resonance spectral analysis and conformational properties of 11-benzoyl-9,9a,10,11-tetrahydro-4H-indolo{4,3-ab}carbazole; Mavromoustakos T et al.; The structure of 11-benzoyl-9,9a,10,11-tetrahydro-4H-indolo {4,3-ab} carbazole, a candidate molecule to possess significant antitumor or antimicrobial activity, was elucidated using a combination of one-dimensional and two-dimensional nuclear magnetic resonance (NMR) techniques . Its conformational properties were studied using a combination of two-dimensional NOESY spectroscopy and molecular modeling . Such information will be of aid to synthetic chemists who aim to develop derivatives of this structure . It may also provide information about the stereoelectronic requirements that govern their activities.

J Infect Dis, 1998 Apr, 177(4), 1003 - 12
Acquisition, carriage, and transmission of pneumococci with decreased antibiotic susceptibility in young children attending a day care facility in southern Israel; Yagupsky P et al.; The prevalence and transmission of antimicrobial drug-resistant pneumococci was studied in 48 children attending a day care facility in southern Israel . Nasopharyngeal cultures were obtained every 2 weeks for 10 months, and antibiotic susceptibility of isolates was determined by disk diffusion and E-test . Relatedness of isolates was investigated by capsular typing, ribotyping, and arbitrarily primed polymerase chain reaction . Pneumococci were recovered during 362 (63%) of 573 fortnights, and 219 (60%) of these isolates showed decreased susceptibility to at least one drug; 154 (43%) were intermediately susceptible to penicillin and 51 (14%) were multiresistant . Combining the different typing methods showed that a limited number of clones circulated in the facility . Clones exhibiting decreased antibiotic susceptibility (especially 23F, intermediately susceptible to penicillin and resistant to trimethoprim-sulfamethoxazole, and multiresistant 6B) were more frequently isolated and persisted longer than did fully susceptible clones . By multivariate analysis, carriage of organisms with decreased antibiotic susceptibility was associated with young age, female sex, winter season, and exposure to antimicrobial drugs during the previous month.

Curr Microbiol, 1998 Apr, 36(4), 212 - 5
The effects of environmental conditions on the in vitro activity of selected antimicrobial agents against Escherichia coli; Nanavaty J et al.; Various environmental conditions likely to be encountered at a nidus of infection were evaluated for their effect on selected classes of antimicrobial agents . The minimum inhibitory concentration (MIC) of several aminoglycosides (apramycin, kanamycin, gentamicin, tobramycin, amikacin), tetracycline, and chloramphenicol for five strains of E . coli were unchanged by temperature (35 degrees-39.5 degrees C), atmosphere (aerobic to anaerobic), pH > 7, NaCl concentration (up to 150 mM), zinc concentration (up to 50 mM), and manganese (up to 10 mM) . However, the aminoglycoside MICs were increased up to fivefold at pH < 6.5 . Magnesium and calcium ion concentrations >10 mM and ferric iron concentrations >/=10 mM increased aminoglycoside MICs from 3.66- to 8-fold . Tetracycline MICs were increased 1.2- to 6.5-fold when the concentration of magnesium or calcium was >/=10 mM . The results of this in vitro study might provide insight into the effects of local in vivo environmental conditions on several classes of antimicrobial agents.

Peptides, 1998, 19(3), 421 - 5
Thrombin-sensitive peptide linkers for biological signal-responsive drug release systems; Tanihara M et al.; We have previously reported an elevation of thrombin-like activity in infected wound exudates . Therefore, using this enzymatic activity as a biological signal, a system which can release an antimicrobial drug at infected wounds was investigated . In this paper, we report thrombin-sensitive peptide linkers, the key component of this system . Starting from amino acid sequences of the cleavage site in fibrinogen, which is the substrate of thrombin, we synthesized some thrombin-sensitive peptide linkers . We constructed devices in which the thrombin-sensitive peptide linker interconnected between polyvinyl alcohol hydrogel and gentamicin . The device was able to release gentamicin in response to thrombin.

J Antimicrob Chemother, 1998 Feb, 41(2), 267 - 72
Surgical prophylaxis in Belgian hospitals: estimate of costs and potential savings; Sasse A et al.; Between 1991 and 1995 the Belgian National Program for Surveillance of Hospital Infections (NSIH) collected data on perioperative antibiotic prophylaxis in 72 acute care hospitals . From the costs of prophylactic antibiotics for six categories of surgical procedure and from discharge summaries for hospitalization episodes nationwide, annual drug costs were estimated for 73% of Belgian surgical activity . Costs of antibiotics used in these surgical activities were estimated at 386-410 million Belgian francs (Bf) per year (US$12.1-12.9 million) . After agreeing recommendations for best practice, the hypothetical costs of 'optimal' antimicrobial prophylaxis were calculated for the same selection of surgical procedures . It was calculated that savings of at least 194 million Bf (US$6.1 million) could be made if recommendations were followed closely . Only the costs borne by the National Health Insurance Institute for reimbursement of the dispensed drugs were considered in this study . Other direct costs, such as those related to drug storage, dispensing and administration, were not included.

J Ethnopharmacol, 1998 Feb, 60(1), 91 - 6
Antimicrobial activity of aerial parts of Drosera peltata Smith on oral bacteria; Didry N et al.; The antimicrobial activity of extracts of aerial parts of Drosera peltata Smith against oral bacteria was investigated using agar diffusion and dilution micromethods . The chloroformic extract, active against all the bacteria tested, showed the most significant antimicrobial properties . Plumbagin, isolated from the extract, is the active principle . Results obtained suggest that Drosera peltata extract could be used in the treatment of oral infectious diseases like dental caries and periodontitis.

J Ethnopharmacol, 1998 Feb, 60(1), 1 - 8
Which extractant should be used for the screening and isolation of antimicrobial components from plants?
Eloff JN.
Freeze dried and finely ground leaves of two plants with known antimicrobial activity, Anthocleista grandiflora and Combretum erythrophyllum were extracted with acetone, ethanol, methanol, methylenedichloride, methanol/chloroform/water and water at a 1 to 10 ratio in each case . The quantity and diversity of compounds extracted, number of inhibitors extracted, rate of extraction, toxicity in a bioassay, ease of removal of solvent and biological hazard were evaluated for each extractant . An arbitrary scoring system was developed to evaluate the above parameters for the different extractants . Acetone gave the best results with these plants with an arbitrary value of 102 followed by methanol/chloroform/water (81), methylene dichloride (79), methanol (71), ethanol (58) and water (47) . Four five minute sequential extractions of very finely ground A . grandiflora shaking at a high rate extracted 97% of the total antimicrobial activity.

Klin Lab Diagn, 1998 Jan, (1), 44 - 6
{Method of quantitative assessment of antimicrobial effects of iodine-containing preparations}; Livitskii VI et al.; Iodine-containing preparations were studied by UV spectral analysis . Water-soluble composition of 1,3-diethylbenzimidasolium triiodide is inactivated in the presence of meat-peptone broth . Dissolving of these preparations in a mixture of acetone and stearic acid does not change the physicochemical properties or impair the antibacterial effect . A high antibacterial effect of 12 iodine-containing compounds has been demonstrated: 15-min exposure suppressed the growth of bacteria at the minimal concentration of 0.1-1.0 microgram/ml.

Vet Clin North Am Food Anim Pract, 1998 Mar, 14(1), 141 - 50
National surveillance for antibiotic resistance in zoonotic enteric pathogens; Tollefson L et al.; Treatment of food-producing animals with antimicrobial agents that are important in human therapy may present a public health risk by the transfer of resistant zoonotic pathogens from animals to humans . Resistant bacteria can diminish the effectiveness of antibiotics and demand the use of more expensive or less safe alternatives . In 1996, the Centers for Disease Control (CDC), United States Department of Agriculture (USDA), and Food and Drug Administration (FDA) established the National Antimicrobial Monitoring System to prospectively monitor changes in antimicrobial susceptibilities of zoonotic pathogens from human and animal clinical specimens, healthy farm animals, and carcasses of food-producing animals at slaughter plants . This article describes the development, implementation, and objectives of the monitoring system and presents initial data generated by the system.

J Dairy Sci, 1998 Feb, 81(2), 403 - 10
Antibiotics commonly used to treat mastitis and respiratory burst of bovine polymorphonuclear leukocytes; Hoeben D et al.; The in vitro effects of six doses (2 x 10(-3) to 2 x 10(-8) M) of antimicrobial drugs that are frequently used in udder infusions on the capacity of bovine blood polymorphonuclear neutrophilic leukocytes to generate reactive oxygen species were studied by the measurement of luminol-dependent chemiluminescence after stimulation with phorbol 12-myristate 13-acetate . All drugs, except cloxacillin, significantly decreased chemiluminescence at the highest dose . Doxycyline induced the most severe inhibition, followed by neomycin and dihydrostreptomycin . The effect of ampicillin was due to the scavenging of reactive oxygen species and interactions with luminol . The inhibition observed with oleandomycin, neomycin, lincomycin, and dihydrostreptomycin was not due to direct effects on the production of oxidative metabolites but rather to interference with other components involved in the production of light, such as interference with the interaction between luminol and the myeloper-oxidase-H2O2-halide system . The deleterious effects of doxycycline can be explained by several factors: decreased production of superoxide, yellow color, the scavenging of reactive oxygen species, and Ca2+ chelating effect . In conclusion, the results of this study show that antibiotics may affect neutrophil function at concentrations that are reached in the mammary gland after local and repeated administration.

Zentralbl Hyg Umweltmed, 1998 Feb, 200(5-6), 443 - 56
{Antiseptic efficacy and acceptance of Octenisept computed with common antiseptic mouthwashes}; Kramer A et al.; The efficacy of common antiseptic mouth rinses was evaluated in a study with healthy volunteers . Octenisept and Cetylpyridiniumchlorid had a significant stronger impact on the microbial burden of the oral cavity than Chlorhexidin (Corsodyl) immediately and 10 min after the application . Dobendan (contains Cetylpyridiniumchlorid) showed a better antimicrobial effect than Corsodyl immediately after application, after 10 min an increasing loss of efficacy was noted . The antiseptic efficacy of hexetidin-based Gurfix was very similar to the efficacy observed with Corsodyl from the start of the antiseptic treatment until 1 h later . Acriflavine-solution (0.2% m/v) was significantly less efficient after 10, 30 and 60 min compared to Corsodyl . The antimicrobial impact of Fluomint-Lysoform was very similar to the effect of rinsing with dest . sterile water . A subjective assessment of taste and smell of the mouth rinse solutions concludes the evaluation . Further methodological aspects for a common test guideline for antiseptic mouth rinse solutions are discussed.

AJR Am J Roentgenol, 1998 Apr, 170(4), 1035 - 9
Percutaneous treatment of liver abscesses: needle aspiration versus catheter drainage; Rajak CL et al.; OBJECTIVE: This study was designed to determine and compare the efficacy of sonographically guided percutaneous needle aspiration and percutaneous catheter drainage in the treatment of liver abscesses . SUBJECTS AND METHODS: In a randomized study, 50 patients (38 males and 12 females; age range, 2-72 years; average age, 35 years) with liver abscesses (amebic, 20; pyogenic, 11; indeterminate, 19) underwent either percutaneous needle aspiration (n = 25) or catheter drainage (n = 25) along with appropriate antimicrobial therapy . In patients assigned to the needle aspiration group, an 18-gauge needle was used to aspirate the abscess cavity . Repeated aspiration was attempted only once in each patient not responding to the first aspiration; nonresponse to the second aspiration was considered failure of treatment, and these patients were given catheter drainage (however, these patients were not included in the catheter drainage group) . For catheter drainage, 8- to 12-French catheters were introduced into the abscess cavity using the Seldinger technique . In patients with multiple abscesses (seven in aspiration group and five in catheter group), all the abscesses except those smaller than 3 cm were subjected to percutaneous treatment . Patients were followed up to assess the outcome of the percutaneous treatment, length of hospital stay, and development of any complications . Sonography was performed every third day during hospitalization . After discharge of the patient, periodic clinical and sonographic examinations were done until total resolution of abscesses was achieved . RESULTS: Although percutaneous needle aspiration was successful in only 15 (60%) of the 25 patients after one (n = 11) or two (n = 4) aspirations, catheter drainage was curative in all 25 patients (100%) (p < .05) . Among the successfully treated patients, the average time for clinical improvement and the mean hospital stay were similar in the two treatment groups . Although the average time needed for a 50% reduction in the size of the abscess cavity was significantly (p < .05) greater in the aspiration group than in the catheter group (11 days versus 5 days), the average time taken for total resolution of abscess was the same (15 weeks) in both groups . No major complications were encountered . No relapse was documented on clinical and sonographic examination during follow-up, which ranged from 8 to 37 weeks . CONCLUSION: Our results show that percutaneous catheter drainage is more effective than needle aspiration in the treatment of liver abscesses . Needle aspiration, if limited to two attempts, has a high failure rate.

Clin Exp Immunol, 1998 Mar, 111(3), 597 - 603
Induction of nitric oxide (NO) synthesis in murine macrophages requires potassium channel activity; Lowry MA et al.; The activation of macrophages for antimicrobial responses is a multistage event involving numerous intracellular signalling cascades that makes possible target cell destruction by these effector cells . This study examined the effects of different potassium channel inhibitors and activators on the NO production of murine macrophage-like cell lines P388D.1 and B10-4(S) . We found that the potassium channel inhibitors tetraethylammonium, 4-aminopyridine, and quinine caused dose-dependent reductions in the NO production of macrophages, and that the potassium channel activator, minoxidol, caused a dose-dependent enhancement of NO production . The inhibition of NO production was due to involvement of potassium channels in the priming stage of macrophage activation, since pretreatment with the priming agent interferon-gamma partially restored the NO response of the macrophages . The results of this study demonstrate a link between potassium channel activity and the activation of anitimicrobial functions of murine macrophages.

Am J Med, 1998 Jan, 104(1), 17 - 27
Variations in antimicrobial use and cost in more than 2,000 patients with community-acquired pneumonia; Gilbert K et al.; PURPOSE: To assess the patterns of antimicrobial use, costs of antimicrobial therapy, and medical outcomes by institution in patients with community-acquired pneumonia . PATIENTS AND METHODS: The route, dose, and frequency of administration of all antimicrobial agents prescribed within 30 days of presentation were recorded for 927 outpatients and 1328 inpatients enrolled in the Pneumonia Patient Outcomes Research Team (PORT) multicenter, prospective cohort study . Total antimicrobial costs were estimated by summing drug costs, using average wholesale price for oral agents and institutional acquisition prices for parenteral agents, plus the costs associated with preparation and administration of parenteral therapy . Thirty-day outcome measures were mortality, subsequent hospitalization for outpatients, and hospital readmission for inpatients . RESULTS: Significant variation (P <0.05) in prescribing practices occurred for 17 of the 23 antimicrobial agents used in outpatients across 5 treatment sites, and for 18 of the 20 parenteral agents used in inpatients across 4 treatment sites . The median duration of antimicrobial therapy for treatment site ranged from 11 to 13 days for outpatients (P=0.01), and from 13 to 15 days for inpatients (P=0.49) . The overall median cost of antimicrobial therapy was $12.90 for outpatients, and ranged from $10.80 to $58.90 among treatment sites (P <0.0001) . The overall median cost of antimicrobial therapy was $228.70 for inpatients, and ranged from $183.70 to $315.60 among sites (P <0.0001) . Mortality and hospital readmission for inpatients were not significantly different across sites after adjusting for baseline differences in patient demographic characteristics, comorbidity, and illness severity . Although subsequent hospitalization for outpatients differed by site, the rate was lowest for the site with the lowest antimicrobial costs . CONCLUSION: Variations in antimicrobial prescribing practices by treatment site exist for outpatients and inpatients with community-acquired pneumonia . Although variation in antimicrobial prescribing practices across institutions results in significant differences in antimicrobial costs, patients treated at institutions with the lowest antimicrobial costs do not demonstrate worse medical outcomes.

Clin Ter, 1997 Dec, 148(12), 617 - 22
{Effects of the triple therapy in the eradication of Helicobacter pylori: comparison of 3 different antibiotics}; Leri O et al.; To compare the effectiveness, in eradicating Helicobacter pylori infection, of three different antibiotics in combination with omeprazole and metronidazole, in order to establish which might be best in clinical practice . One hundred twenty three patients with HP-positivity, assessed by CLO-test and histology were studied . They were randomly assigned to the following therapies: clarithromycin (500 mg thrice daily) for 14 days, amoxycillin (twice daily) for 14 days, azithromycin (500 mg once daily) for 6 days, in combination with omeprazole (twice daily for 20 days and once for one month plus metronidazole (500 mg twice days) for 10 days . The eradication rate, among the three groups, was 97%, 80% and 68% respectively (p = 0.009); no statistical differences were remarked also between the group treated with amoxicyllin and that with clarithromycin, and between the group treated with amoxicyllin and that with azithromycin; there was only a statistical difference between the group treated with azithromycin and that with clarithromycin (p = 0.005) . The Authors suggest that all the three antibiotics are effective in curing Helicobacter pylori infection and, that, the various use of the three antimicrobials should be evaluated from time to time on the basis of clinical data of the patients.

Z Naturforsch {C}, 1998 Jan-Feb, 53(1-2), 60 - 4
A new inhibitor of synovial phospholipase A2 from fermentations of Penicillium sp . 62-92; Witter L et al.; Penidiamide, a new tripetide containing dehydrotryptamine, glycine and anthranilic acid linked together by two amide bonds, and oxindole were isolated from submerged cultures of Penicillium sp . 62-92 . Both compounds preferentially inhibited human synovial phospholipase A2, penidiamide with an IC50 of 30 microM and oxindole of 380 microM . With the exception of U 937 cells (leukemia, human), no cytotoxic activities were detected against HL-60- (leukemia, human), HeLa S3- (epitheloid carcinoma, human), BHK 21- (kidney fibroblasts, hamster), and L1210-cells (leukemia, mouse) . No antimicrobial activity was detected for oxindole, and only weak antibacterial activity for penidiamide . The structure of penidiamide was elucidated by spectroscopic methods.

J Periodontol, 1998 Jan, 69(1), 34 - 40
The expression of collagen I and XII mRNAs in Porphyromonas gingivalis-induced periodontitis in rats: the effect of doxycycline and chemically modified tetracycline; Karimbux NY et al.; Tissue remodeling is a dynamic state in which a balance is achieved between the proteolytic breakdown and synthesis of the extracellular matrix . Type I collagen is a major component of the gingival connective tissue (GCT) and the periodontal ligament (PDL) throughout development, while type XII collagen has been found in the mature forms of these tissues . The purpose of this study was to investigate the effects of periodontitis on the expression of type I and XII collagen and subsequently to investigate the effects of doxycycline (DOXY) and chemically modified non-antimicrobial tetracycline (CMT-1) on the expression of these molecules in this model . Adult barrier-raised male Sprague-Dawley rats were inoculated with Porphyromonas gingivalis obtained from humans to create the experimental periodontitis . The animals with the P . gingivalis-induced periodontitis were then split into the following groups: Group A served as infected untreated controls (PGI group); group B was treated with doxycycline (DOXY group); and group C was treated with chemically modified tetracycline-1 (CMT-1 group) . Group D contained uninfected animals that served as uninfected controls (NIC group) . The expression of type I and XII collagen mRNAs was examined by in situ hybridization in each group, with the co-expression of these molecules representing mature and functional gingival connective tissue . In the NIC group, cells hybridized with digoxygenine-labeled cDNA probes encoding rat alpha2(I) or alpha1(XII) collagens were found distributed uniformly throughout the periodontal connective tissue . The PGI group showed little hybridization in the areas of infection, while both the DOXY and CMT-1 groups showed co-expression of the alpha2(I) and alpha1(XII) probes in the GCT and coronal part of the PDL . This study demonstrates that doxycycline and CMT-1 moderate or reduce the inhibitory effects of periodontal infection on the expression of type I and type XII collagen mRNAs . These results suggest that doxycycline and a form of non-antimicrobial tetracycline, chemically modified tetracycline-1, can reduce periodontal destruction by reversing the inhibitory effect of periodontal infection on collagen synthesis.

Int J Tuberc Lung Dis, 1998 Mar, 2(3), 187 - 99
Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance; Lipsitch M et al.; SETTING: Patient non-compliance and/or spatial heterogeneity in drug concentration or effectiveness may contribute to the emergence of drug resistance during multiple-drug chemotherapy of tuberculosis . OBJECTIVE: Using mathematical models of mycobacterial population dynamics under antimicrobial treatment, to assess the effects of non-compliance, heterogeneity and other factors on the success of treatment . DESIGN: A mathematical model is used to generate predictions about the ascent of drug resistance in treated hosts with non-compliance and/or a 'protected compartment' of bacteria where only one drug is active; simulations of a more realistic version of this model take into account random mutation, and different assumptions about the size of, and growth rate of bacteria in, the protected compartment . RESULTS: The existence of a protected compartment can increase the likelihood of resistance to the single drug active in that compartment, but only if bacteria resistant to that drug can grow in the protected compartment or if the host is non-adherent to the treatment regimen . However, the protected compartment may also slow the ascent of bacteria resistant to drugs not active in it (e.g . isoniazid) by providing a reservoir of non-selected mycobacteria . The model predicts that relative rates of killing are more important than mutation rates in determining the order in which resistant mutants ascend . Model predictions, in combination with data about drug resistance patterns, suggest that non-compliance, but not heterogeneity, is an important cause of treatment failure . CONCLUSION: Patterns of acquired drug resistance may be used to infer processes of selection during treatment; mathematical models can aid in generating predictions about the relative impacts of treatment parameters in the evolution of resistance, and eventually in suggesting improved treatment protocols.

J Am Coll Cardiol, 1998 Mar 15, 31(4), 827 - 32
Endovascular presence of viable Chlamydia pneumoniae is a common phenomenon in coronary artery disease; Maass M et al.; OBJECTIVES: We sought to examine coronary arteries for the presence of viable bacteria of the fastidious species Chlamydia pneumoniae . BACKGROUND: The respiratory pathogen C . pneumoniae has been implicated in the pathogenesis of coronary artery disease (CAD) . Previous studies have demonstrated an antichlamydial seroresponse to be a cardiovascular risk factor and coronary atheromata to contain chlamydial components in varying proportions . Endovascular demonstration of replicating bacteria is required to provide evidence for an infectious component in CAD and a rationale to discuss antimicrobial therapy . METHODS: Myocardial revascularization was performed in 70 patients . Atherosclerotic lesions from 53 coronary endarterectomy and 17 restenotic bypass samples were cultured and subjected to nested polymerase chain reaction (PCR) for C . pneumoniae . Antichlamydial immunoglobulin G (IgG), IgA and IgM was examined by microimmunofluorescence . RESULTS: Viable C . pneumoniae was recovered from 11 (16%) of 70 atheromata, and chlamydial deoxyribonucleic acid (DNA) was detected in 21 (30%) of 70 atheromata; 17 nonatherosclerotic control samples were PCR-negative (p < 0.01) . Fifteen (28%) of 53 endarterectomy and 6 (35%) of 17 bypass samples were PCR-positive . DNA sequencing of six different PCR products did not reveal differences between coronary isolates and respiratory reference strains, suggesting that common respiratory strains gain access to the systemic circulation . Serologic results did not correlate with direct detection results and did not identify individual endovascular infection . CONCLUSIONS: A significant proportion of atherosclerotic coronary arteries harbor viable C . pneumoniae . This finding supports the hypothesis of a chlamydial contribution to atherogenesis . Whether chlamydiae initiate atherosclerotic injury, facilitate its progression or colonize atheromata is unknown . However, the endovascular presence of viable bacteria justifies a controlled clinical investigation of antimicrobial treatment benefit in the therapy and prevention of CAD.

Arch Pharm (Weinheim), 1998 Feb, 331(2), 54 - 8
Research on potentially bioactive aza and thiaza polycyclic compounds containing a bridgehead nitrogen atom . Synthesis and antimicrobial activity of some pyrrolo{1,2,3-de}-1,4-benzothiazines, Part 2; Armenise D et al.; Acid catalyzed cyclization reactions of both 3-alkyl- and 3-aryl-substituted N-(2,2-dialkoxyethyl)-3,4-dihydro-2H-1,4-benzothiazines (2) lead to 2,3-dihydro-pyrrolo{1,2,3-de}-1,4-benzothiazines (3) . The pyrrolobenzothiazine structure was deduced on the basis of 2D 1H NMR-NOESY experiments and fully determined by X-ray data . Compounds 3a-c showed poor antibacterial activity . However, the 3-phenyl-N-(2,2-dimethoxyethyl)-3,4-dihydro-2H-1,4-benzothiazine (2b') showed antifungal activity against Aspergillus niger 16-fold greater than miconazole.

Pediatr Dent, 1998 Jan-Feb, 20(1), 28 - 36
Bacteremia of dental origin and antimicrobial sensitivity following oral surgical procedures in children; Roberts GJ et al.; METHODS: The prevalence and intensity of bacteremia of dental origin were examined in 207 children divided into four groups: a baseline with no surgical intervention (group I), after a single tooth extraction (group II), multiple tooth extraction (group III), and mucoperiosteal flap elevation (group IV) . The bacterial isolates were grown using a broth culture (Bactec) and lysis centrifugation (Paediatric Isolator) techniques . Dental plaque deposits, gingivitis, spontaneous gingival bleeding and the presence/absence of a dental abscess were recorded and their relationship to bacteremia assessed . RESULTS: The broth culture was positive for group I 11% of the time, group II for 43%, group III for 54%, and group IV for 43% . The Paediatric Isolator system was found to be a poor method for detecting bacteremia, having only one quarter the sensitivity of the broth culture technique . When organisms were isolated, the intensity of bacteremia ranged from 1 to 3400 colony forming units per milliliter (cfu/mL) . Bacterial isolates were susceptible to most of the antibiotics recommended for antibiotic prophylaxis, but erythromycin, gentamycin, penicillin G, and teicoplanin were only 80% (or less) effective in their efficacy while chlorhexidine, amoxicillin, clindamycin, and vancomycin were between 92 and 100% effective . CONCLUSIONS: The antibiotics commonly used for an oral and/or parenteral prophylaxis are likely to be effective on at least 80% of occasions with most of them effective on 100% of occasions.

Clin Infect Dis, 1998 Mar, 26(3), 695 - 701
Inpatient emergencies encountered by an infectious disease consultative service; Luk WK et al.; The spectrum of infectious disease (ID) emergencies in hospitalized patients was assessed in a prospective study of 3,626 inpatient ID consultations in a 1,350-bed teaching hospital . ID emergencies, defined by a need or anticipated need for advanced life support or by irreversible organ damage leading to permanent functional loss, were encountered in 175 patients . Infections of the central nervous system (26.3%), cardiovascular system (14.9%), alimentary system (13.1%), and lower respiratory tract (7.4%) and adverse reactions to antimicrobial agents (7.4%) were most common . In 18.9% of the cases, the referring clinicians were unaware of the emergency at the time of referral . Drug reactions (46.1%), severe alimentary and peritoneal infections (32.0%), upper respiratory tract infections (28.6%), and skin and soft-tissue infections (27.3%) were most frequently missed . The emergency ID conditions were not recognized because they had an atypical presentation (51.5%), were not commonly seen in the referring specialty (24.2%), were due to rare organisms (15.2%), or had unusual anatomical sites of involvement (9.1%) . A close liaison between clinicians and the ID team is crucial for recognition of ID emergencies at their early stages so that appropriate investigations and management can be instituted expediently, before the occurrence of irreversible damage.

Rev Med Chir Soc Med Nat Iasi, 1995 Jan-Jun, 99(1-2), 164 - 6
{The synthesis and biological activity of new disubstituted carbanion ylides from pyridazine}; Caprosu M et al.; Continuing the investigations in view obtaining new carbon-nitrogen stable dissiniu-ilydes, were obtained new 3-phenyle-pyridaziniu-ylides carbanion disubstituted . The antimicrobial and antifungus action of the products VIa, VIb, VIIa, VIIb and VIIc also studied.

Pol Merkuriusz Lek, 1997 Dec, 3(18), 291 - 4
{Current views on the pathophysiology of bacterial meningitis--new therapeutic possibilities?}; Kepa L; Despite the introduction of numerous antimicrobial therapeutic advances, the morbidity and mortality associated with bacterial meningitis remain high . New understanding of the pathogenesis and molecular pathophysiology of bacterial meningitis have led to the development of innovative, adjunctive treatment strategies in the hopes of improving outcome from this disorders . Studies in animal models have demonstrated, that the inflammatory response resulting from bacterial invasion of the subarachnoid space is due in large part to the activity of host-derived mediators (cytokines) . This inflammatory response is responsible for the long-term neurological sequelae and death associated with bacterial meningitis . Experimental studies have demonstrated, that attenuation of the inflammatory response by anti-inflammatory agents may be useful in preventing many of the pathophysiologic consequences of bacterial meningitis . Numerous potential therapeutic agents, that may limit inflammation of the subarachnoid space have been and are being developed, and trials in animal models and in humans are under way . There are: corticosteroids (dexamethasone), non-steroidal anti-inflammatory agents, pentoxifylline, anti-leukocyte CD-18 receptor antibodies, specific cytokine antagonists, antagonists of Platelet-Activating Factor (PAF) and others . Safe and effective agents with demonstrated efficacy as adjuvants to bactericidal antimicrobial agents in the therapy for bacterial meningitis in humans may improve the prognosis of this disease.

Semin Perinatol, 1998 Feb, 22(1), 50 - 63
The role of intravenous immunoglobulin for the prevention and treatment of neonatal sepsis; Jenson HB et al.; The use of intravenous immunoglobulin (IVIG) for the prevention and treatment of sepsis in neonates is appealing because of the relative immunodeficiency of the neonate and the desire to improve the relatively poor outcome even with optimal antimicrobial treatment . The effectiveness of IVIG for these uses has been studied in numerous prospective as well as retrospective small and large trials that have had discordant conclusions . Meta-analysis demonstrates the marginal but significant benefit of prophylactic IVIG administered shortly after birth in preventing early onset sepsis in premature low birth weight newborns (P = .0193, two-sided) . The expense of prophylactic use of IVIG administration for the relatively large premature newborn population given the minimal benefit as demonstrated by original studies and by meta-analysis is not justified . In contrast, meta-analysis of studies of IVIG for the treatment of neonates with sepsis shows a significant and unequivocal sixfold decrease in the mortality rate (P = .007, two-sided) when IVIG is administered in addition to standard therapies . The additional benefit of decreasing the risk for acute mortality indicates that the inclusion of IVIG should be considered a part of the routine therapy of neonatal sepsis.

Curr Opin Immunol, 1998 Feb, 10(1), 41 - 4
Antimicrobial peptides of vertebrates; Ganz T et al.; The past year brought several discoveries that focused attention on antimicrobial peptides on epithelial surfaces . The malfunction of these substances was implicated as a cause of airway infections in cystic fibrosis . Other highlights included new insights into the relative selectivity of antimicrobial peptides for microbial membranes, their primary site of action.

Curr Opin Immunol, 1998 Feb, 10(1), 16 - 22
Antimicrobial proteins in induced plant defense; Fritig B et al.; During the past few years a wide spectrum of plant antimicrobial proteins has been detailed, and enhanced resistance has been obtained by introducing the corresponding genes into crop species to produce transgenic lines . With the aim of manipulating the plant signals that regulate an array of defense responses, the most intense research focuses on the avr-R-mediated recognition events and elucidation of the subsequent signaling pathways that govern the activation of genes encoding antimicrobial proteins.

Am J Health Syst Pharm, 1998 Mar 1, 55(5), 463 - 6
Storage of extemporaneously prepared ophthalmic antimicrobial solutions; Charlton JF et al.; The feasibility of long-term storage of commonly used ophthalmic antimicrobial solutions was studied . Solutions of tobramycin 15 mg/mL (as the sulfate salt), cefazolin 33 mg/mL (as the sodium salt), and vancomycin 50 mg/mL (as the hydrochloride salt), each in artificial tears, were prepared with aseptic technique . Ten 15-mL portions of each solution were prepared; five of each were stored at 4 degrees C and the other five at 25 degrees C . Samples of each portion were tested before storage and 7, 14, 21, and 28 days after preparation for osmolality, pH, and antimicrobial activity . For the tobramycin solution there were no differences in osmolality or the zone of inhibition associated with temperature or time . The pH dropped between days 0 and 7 at both temperatures . For the cefazolin solution there were no differences in osmolality associated with temperature or time . The pH was higher in portions stored at 25 degrees C than at 4 degrees C and increased over time in portions stored at either temperature . The zone of inhibition was larger for portions stored at 4 degrees C than at 25 degrees C but did not change over time . For the vancomycin solution there were no differences in osmolality associated with temperature or time . The pH did not differ between portions stored at 4 and 25 degrees C but dropped sharply at both temperatures between days 0 and 7 . The zone of inhibition did not differ with temperature or time . The tobramycin solution could be stored for 28 days at room temperature and the cefazolin solution for 28 days under refrigeration . The pH of the vancomycin solution changed too quickly for storage to be recommended.

Recenti Prog Med, 1997 Dec, 88(12), 566 - 73
{Respiratory medicine in the aged . Therapeutic problemsd}; Leonardi R et al.; Chronic obstructive pulmonary disease (COPD) is very common in the elderly, and its treatment needs special concern . Data from two clinical studies (in-patients of an Internal Medicine Department and Nursing-Home, respectively) have been evaluated in order to compare therapeutic approaches to COPD in three separate settings: home, hospital and Nursing-Home . Less than 50% of the overall patients received medical treatment according to the guidelines emerged in the literature . Although cardiovascular problems were highly common in out-patients, their bronchodilator therapy included systemic beta 2-agonists . Theophylline was the main drug prescribed to in-patients discharged from hospital, although inhaling beta 2-agonists were also recommended in few cases . Topical steroids have been widely used . Nursing-Home patients received mostly systemic steroids and few of them had theophylline and inhaling steroids . Anti-cholinergic drugs have never been employed in the overall population of elderly patients . Data concerning medical treatment of infectious respiratory diseases of Nursing-Home patients (both with and without COPD) have also been evaluated . Antimicrobial therapy has been performed according to the special needs of the elderly . During COPD reacutizations, beta 2-agonists and, again, theophylline consumption increased.

Chirurg, 1998 Jan, 69(1), 28 - 37
{Ruptured aortic aneurysm as an unexpected finding in laparotomy for acute abdomen}; Schildberg FW et al.; The ruptured abdominal aortic aneurysm as an incidental finding in emergency laparotomy for acute abdominal symptoms is a rare event . For this reason it is more important to know the necessary diagnostic and therapeutic strategies . Nowadays sonography facilitates the preoperative diagnosis . The performance of an additional computed tomography or angiography depends on the clinical appearance of the patient . In hemodynamically instable patients with a ruptured aneurysm, an immediate laparotomy is mandatory . If intraoperatively the aortic aneurysm has a diameter of more than 5 cm and shows no signs of rupture, implantation of an aortic prosthesis is indicated . This procedure has also priority when patients with a ruptured aneurysm are suffering from an additional abdominal disease . If additional septic reasons are diagnosed intraoperatively, the abdominal operation has to be performed synchronously with the aortic prosthesis . Alternatively, the use of an antimicrobial vascular prosthesis or resection of the aortic aneurysm with extra-anatomic bypass has to be considered . The technical difficulty of the operation is in the control of the proximal aorta . The lethality of operations for ruptured aneurysm has been consisted high (between 21 and 70%) in the past . In an elective operation, mortality has how improved up to 5% . This indicates that the essential prognostic factors, degree of retroperitoneal hematoma and hemorrhagic shock, and the condition of the patient, are not influenced by modern patient management . However, a further dominant prognostic parameter for lethality, how qualified the surgeon is in vascular surgery, can be influential.

Biochemistry, 1998 Mar 17, 37(11), 3623 - 37
Solution structure of Ace-AMP1, a potent antimicrobial protein extracted from onion seeds . Structural analogies with plant nonspecific lipid transfer proteins; Tassin S et al.; The three-dimensional solution structure of Ace-AMP1, an antifungal protein extracted from onion seeds, was determined using 1H NMR spectroscopy and molecular modeling . This cationic protein contains 93 amino acid residues and four disulfide bridges . Its structure was determined from 1260 NOE-derived distance restraints and 173 dihedral restraints derived from NOEs and 3JCaHNH coupling constants . The global fold involves four helical segments connected by three loops and a C-terminal tail without regular secondary structures, except for a 3(10)-helix turn and a beta-turn . The most striking feature is the absence of any continuous cavity running through the whole molecule as found in recently determined structures of nonspecific transfer proteins extracted from wheat and maize seeds, although their global folds are very similar . Consistent with the absence of a cavity in the core of Ace-AMP1, it was found that this protein, in contrast to ns-LTPs, does not bind fluorescently labeled phospholipids in solution . On the other hand, Ace-AMP1 is able to interact with phospholipid membranes as shown by the release of carboxyfluorescein from the lumen of artificial liposomes and by the induction of alterations in fluorescence polarization of fluorescently labeled phospholipids embedded in artificial liposomes.

J Chromatogr B Biomed Sci Appl, 1998 Feb 13, 705(2), 323 - 9
Sensitive liquid chromatographic technique to measure isoniazid in alveolar cells, bronchoalveolar lavage and plasma in HIV-infected patients; Delahunty T et al.; The need to monitor the effectiveness of antimicrobial drugs in treating opportunistic infections such as tuberculosis in HIV-infected patients requires the development of sensitive assays . A suitable HPLC method was developed to measure the concentration of isoniazid (INH) in plasma 1 h after a standard 300 mg dose and to detect the low levels typically found in alveolar cells obtained by bronchoalveolar lavage of subjects maintained on a standard regimen of the drug . Following extraction with a chloroform-butanol mixture, the INH was back-extracted into dilute acid which was subsequently analyzed by HPLC using a CN reversed-phase column and an acetonitrile-isopropanol based mobile phase . Another HPLC method was developed using direct injection and a polymer based column to measure minute concentrations of INH in the cell-free lavage . In both systems, detection of the drug was accomplished with a sealed coulometric detector (+0.6 V) capable of giving a consistent daily response without adjustment . When saline, cellular extracts and plasma from untreated subjects were spiked with various amounts of INH and analyzed, the lowest level of quantitation was 10, 25 and 100 ng/ml, respectively . Calibration curves showed good linearity when spiked concentrations were compared to peak areas (r=0.991, 0.993 and 0.998, respectively) . Alveolar cell extracts and cell-free bronchoalveolar fluid from HIV-positive patients maintained on a standard INH regimen had detectable levels of INH 4 h after a 300 mg oral dose . The plasma INH at 1 h had a range of 0.3-7.1 microg/ml (n = 50) . Precision studies with plasma spiked at 0.1, 0.5, 1.0 and 5.0 microg/ml revealed within-run coefficients of variation (C.V.s) of 8.9, 7.2, 4.2 and 4.9%, respectively and analytical recoveries of 97, 108, 108 and 98%, respectively . The day-to-day C.V.s for the plasma method were 7.6, 4.9 and 3.8% at concentrations of 0.5, 1.0 and 3.0 microg/ml, respectively . The results suggest that this rugged HPLC technique can quantitate INH in 1 h plasma with good precision and can be used to estimate the very low INH concentrations found in alveolar cells and cell-free lavage recovered from patients undergoing anti-tuberculosis therapy.

J R Soc Health, 1997 Oct, 117(5), 324 - 9
Essential oils and 'aromatherapy': their modern role in healing; Lis-Balchin M; 'Aromatherapy' is one of the most actively growing forms of alternative medicine combining massage together with counselling and a nice odour . Most clients suffer from some kind of stress-related disorder and aromatherapy encourages the healing process largely through relaxation and the relief of stress . Stress is also a major problem in hospitals, hospices and homes for the aged and physically or mentally-challenged . Aromatherapy is welcomed by nurses who want to be closer to their patient and doctors who can refer patients with stress-related disorders who do not respond to conventional medicines . The actual mode of action of essential oils in vivo is still far from known, although there is strong in vitro evidence that essential oils can act as an antimicrobial or antioxidant agent or have a pharmacological effect on various tissues . Studies have shown that essential oils have an effect on brainwaves and can also alter behaviour . It is possible that most of the effect of the oils is probably transmitted through the brain via the olfactory system . Used professionally and safely, aromatherapy can be of great benefit as an adjunct to conventional medicine or used simply as an alternative.

Postgrad Med, 1998 Mar, 103(3), 231 - 8, 243
Helicobacter pylori and peptic ulcer disease . Bridging the gap between knowledge and treatment; Laine L et al.; Eradication of H pylori and cure of peptic ulcer disease are possible if effective regimens are used correctly . Treatment markedly improves clinical outcomes and significantly decreases cost of care . As primary care physicians take a larger role in management of these infections, they need to understand the importance of identifying and treating patients with H pylori-associated peptic ulcer disease . Successful treatment of this infection depends on the appropriate antimicrobial therapy and patient compliance with the chosen regimen.

Probe, 1993 Jan-Feb, 27(1), 18 - 25
A literature review: oral irrigation therapy . The adjunctive roles for home and professional use; Stein M; It is now recognized that there are several different types of periodontal infections . As we learn more about the cause of these diseases, it becomes obvious that we have treatment options . A successful choice of procedures for each individual depends on an accurate diagnosis based on comprehensive data collection of clinical and microbiological findings . Treatment choices include a non-surgical phase which consists of plaque removal, plaque control, scaling, root planing, and the use of chemical agents . For complete debridement of deep pockets, furcations or areas with root surface irregularities, surgical access may be necessary . When considering drug therapy, it must be noted that systemic antibiotics may be necessary to suppress those subgingival periodontal pathogens which have the ability to invade the tissue and resist other methods of eradication . Removal or alteration of pathogenic flora is mandatory to improve a patient's periodontal health . The extensive use of supragingival irrigation as an adjunct for treating gingivitis has led to the interest in subgingival irrigation as a possible adjunct for treatment of periodontal diseases . Targeted lavage and subgingival delivery of effective antimicrobial agents show potential as supplemental office procedures or as a component of a home oral hygiene regime . Additional research is needed to develop more efficacious chemotherapeutic substances than are currently available and to further define the optimum application of each . Substantive medicaments that react specifically against periodontopathic organisms are essential . Exact frequency and duration of professionally-applied and self-administered subgingival irrigation need to be determined for maximum results . Further investigation is required to establish the potential role of adjunctive irrigation and antimicrobial therapy in the treatment of periodontitis . Yet, another important application of irrigation has been recognized . Recently, the American Heart Association revised its guidelines for the prevention of bacterial endocarditis . The amendments to the dentistry sections have been approved by the Council on Dental Therapeutics of the American Dental Association . Included in this text is the recommendation that as an adjunct to antibiotic prophylaxis, sulcular irrigation with chlorhexidine may be useful for those patients considered high risk and/or have poor oral hygiene . Irrigation therapy is undergoing extensive scrutiny in the scientific research community . Presently, considerable conclusive evidence exists to suggest that adjunctive irrigation may play an important role in controlling gingivitis and periodontitis . The overwhelming challenge for any and all successful periodontal therapy will always remain dependent on patient compliance to regular professional and home care.

Antimicrob Agents Chemother, 1998 Mar, 42(3), 703 - 4
In vitro activity of BAY 12-8039, a new fluoroquinolone against mycoplasmas; Bebear CM et al.; The in vitro activity of the fluoroquinolone BAY 12-8039 against 66 strains of different mycoplasma species and 30 strains of Ureaplasma urealyticum was compared with those of three other antimicrobial agents . BAY 12-8039 at 0.5 microg/ml inhibited 100% of all the mycoplasmal and ureaplasmal strains tested . The minimal bactericidal concentrations of BAY 12-8039 increased only two- to eightfold compared to the MICs . Furthermore, they were comparable to those of sparfloxacin and lower than those of doxycycline and clarithromycin.

Antimicrob Agents Chemother, 1998 Mar, 42(3), 666 - 74
Anti-Pneumocystis activities of aromatic diamidoxime prodrugs; Hall JE et al.; Aromatic dicationic compounds, such as pentamidine, have potent antimicrobial activities . Clinical use of these compounds has been restricted, however, by their toxicity and limited oral activity . A novel approach, using amidoxime derivatives as prodrugs, has recently been proposed to overcome these limitations . Although results were presented for amidoxime derivatives of only one diamidine, pentamidine, the authors in the original proposal claimed that amidoxime derivatives would work as effective prodrugs for all pharmacologically active diamidines . Nine novel amidoxime derivatives were synthesized and tested in the present study for activity against Pneumocystis carinii in corticosteroid-suppressed rats . Only three of the nine compounds had significant oral anti-Pneumocystis activity . The bisbenzamidoxime derivatives of three direct pentamidine analogs had excellent oral and intravenous activities and reduced acute host toxicity . These compounds are not likely candidates for future drug development, however, because they have chronic toxic effects and the active amidine compounds have multiple sites susceptible to oxidative metabolism, which complicates their pharmacology and toxicology . Novel diamidoximes from three other structural classes, containing different groups linking the cationic moieties, lacked significant oral or intravenous anti-Pneumocystis activity, even though the corresponding diamidines were very active intravenously . Both active and inactive amidoximes were readily metabolized to the corresponding amidines by cell-free liver homogenates . Thus, the amidoxime prodrug approach may provide a strategy to exploit the potent antimicrobial and other pharmacological activities of selected, but certainly not all, aromatic diamidines.

Antimicrob Agents Chemother, 1998 Mar, 42(3), 521 - 7
Pharmacodynamic evaluation of factors associated with the development of bacterial resistance in acutely ill patients during therapy; Thomas JK et al.; The selection of bacterial resistance was examined in relationship to antibiotic pharmacokinetics (PK) and organism MICs in the patients from four nosocomial lower respiratory tract infection clinical trials . The evaluable database included 107 acutely ill patients, 128 pathogens, and five antimicrobial regimens . Antimicrobial pharmacokinetics were characterized by using serum concentrations, and culture and sensitivity tests were performed daily on tracheal aspirates to examine resistance . Pharmacodynamic (PD) models were developed to identify factors associated with the probability of developing bacterial resistance . Overall, in 32 of 128 (25%) initially susceptible cases resistance developed during therapy . An initial univariate screen and a classification and regression tree analysis identified the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (AUC{0-24}/MIC) as a significant predictor of the development of resistance (P < 0.001) . The final PK/PD model, a variant of the Hill equation, demonstrated that the probability of developing resistance during therapy increased significantly when antimicrobial exposure was at an AUC{0-24}/MIC ratio of less than 100 . This relationship was observed across all treatments and within all organism groupings, with the exception of beta-lactamase-producing gram-negative organisms (consistent with type I beta-lactamase producers) treated with beta-lactam monotherapy . Combination therapy resulted in much lower rates of resistance than monotherapy, probably because all of the combination regimens examined had an AUC{0-24}/MIC ratio in excess of 100 . In summary, the selection of antimicrobial resistance appears to be strongly associated with suboptimal antimicrobial exposure, defined as an AUC{0-24}MIC ratio of less than 100.

Nutr Hosp, 1997 Nov-Dec, 12(6), 277 - 88
{Influence of foods on the absorption of antimicrobial agents}; Fraga Fuentes MD et al.; Understanding the interaction between foods and antimicrobial agents is an aspect of therapy which may have an important clinical repercussion, which is why it must not be forgotten . This study reviews the interactions of foods with the anti-microbial agents which occur at the level of absorption, considering the mechanisms involved . The food-drug interaction can cause an increase, a decrease, or a delay in the bio-availability of the anti-microbial agents; foods may have no affect on the absorption of the anti-microbial agents, or they may improve the gastrointestinal tolerance . The Food and Drug Administration's bioequivalency criteria for considering whether or not there is an alteration in absorption have an orientative function, as generally all studies are conducted on healthy volunteers, but in clinical practice one must consider the physiological and pathological condition of the patient . The composition of the diet as well as the volume of liquid administered are other aspects which should be considered, as these may exert a different effect depending on the type of drug . After ingesting fatty foods, there is an increased absorption of albendazole, griseofulvin, itraconazole, and mebendazole . All foods but especially carbohydrates reduce the absorption of isoniazide . Among the anti-HIV drugs, the following must be administered on an empty stomach: didanosine, indinavir zalcitabine , and zidovudine ; lamivudine can be administered either on an empty or on a full stomach, because although food delays the absorption, it does not affect the amount absorbed; the absorption of stavudine is not affected by foods; ritonavir should be administered together with tile meals, and saquinavir must be administered after ingestion of food . It is advisable to administer clarithromycin together with foods, and azythromycin on an empty stomach; the same holds true for perfloxacin and rifabutine as for lamivudine.

Chest, 1998 Mar, 113(3 Suppl), 211S - 218S
Sequential switch therapy for lower respiratory tract infections: a European perspective; Nathwani D; Traditionally, serious lower respiratory tract infections (LRTIs) are treated in hospital and with parenteral antibiotics . During the past decade, there has been an impetus to reduce the overall cost of antimicrobial therapy . The availability of new oral antibiotics with superior pharmacokinetics profiles and safety has enabled clinicians increasingly to consider their use in managing serious infections effectively . This article reviews the current published literature regarding the practice of switch therapy for LRTIs, examining the evidence for efficacy, safety, appropriate timing of the switch, the economic benefits, and the suitability of various antibiotics . There is an emphasis on comparing current European and US experience and examining key strategies in implementing such programs and means of assessing their impact.

Chest, 1998 Mar, 113(3), 788 - 94
Elevated pleural fluid levels of defensins in patients with empyema; Ashitani J et al.; BACKGROUND: Defensins, also known as human neutrophil peptides, are antimicrobial peptides present in the azurophil granules of neutrophils . We measured their level in pleural effusion in various pulmonary diseases to investigate whether they could be used as a diagnostic marker in the differential diagnosis of specific pleural diseases . PATIENTS AND PARTICIPANTS: We analyzed pleural effusion samples collected from 61 patients, including 50 exudates (11 with empyema, 3 parapneumonic, 15 tuberculous, 18 neoplastic, 3 miscellaneous) and 11 transudates as controls . MEASUREMENTS: Defensins were measured by radioimmunoassay and also analyzed by reverse-phase high-performance liquid chromatography . The concentrations of interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) in pleural effusion fluid were measured by enzyme-linked immunosorbent assay to examine the correlation between these cytokines and defensins . RESULTS: The concentration of defensins in all samples of empyema was >5,100 ng/mL and the mean concentration (13,265.8+/-1,895.2 ng/mL) in these samples was the highest among other groups . The concentration in the other 50 pleural effusion samples tested was <2,800 ng/mL . Defensins were mostly of the mature type in empyema . Pleural effusion levels of IL-8 and G-CSF in patients with empyema were also significantly higher than those in other samples . There was a significant correlation between defensins and IL-8 or G-CSF in pleural effusion fluid (r=0.762, and 0.827, respectively) . CONCLUSIONS: Our results suggest that the high effusion concentrations of defensins in pleural effusion may constitute an important component of the host defense system or may have a cytotoxic role in empyema . Our results also indicate that the high levels of IL-8 and G-CSF in empyema may indirectly explain the elevated levels of defensins by increasing the number of neutrophils in the pleural space.

Am J Surg, 1998 Feb, 175(2), 87 - 90
Duration of antimicrobial prophylaxis in vascular surgery; Hall JC et al.; BACKGROUND: This randomized clinical trial compares the incidence of wound infection after vascular surgery in patients who received prophylaxis using the same antibiotic as either a single-dose or a multiple-dose regimen (until the lines/drain tubes were removed, but not for more than 5 days) . METHODS: Each of the 302 patients who entered the study received ticarcillin 3.0 g/clavulanate 0.1 g (Timentin) intravenously immediately after the induction of anesthesia . Patients randomized to the multiple-dose group received an average of 14.3 doses (range 9 to 20) . RESULTS: The incidence of wound infections was 18% (28 of 153) for patients in the single-dose group and 10% (15 of 149) for patients in the multiple-dose group (P = 0.04; relative risk estimate = 2.00, 95% confidence interval = -1.02 to 3.92) . CONCLUSIONS: A multiple-dose antibiotic regimen, rather than single-dose therapy, provides optimal prophylaxis against wound infection for patients undergoing vascular surgery.

Gen Dent, 1996 Nov-Dec, 44(6), 538 - 43
Antimicrobial management of third molars: survey results for military dentists; Wilhelm RJ et al.; In a survey of military dentists to examine use of antimicrobial agents in the management of third molars, questions addressed use of antibiotics and an antimicrobial rinse in treating pericoronitis and third molar extractions . Results were compared with information from a literature review . According to the survey, a majority of clinicians use antibiotics to treat pericoronitis but not surgical extraction of asymptomatic dental impactions . About 60 percent of respondents use a preoperative rinse with chlorhexidine in treating the third molar conditions discussed . A postoperative rinse with chlorhexidine was used less frequently . Half the respondents listed medicolegal factors in their decisions.

Dent Update, 1997 Jun, 24(5), 204 - 7
Locally delivered antimicrobials in periodontal therapy; Greene PR; The rapid growth in our understanding of the pathogenesis of periodontal disease has led to a change in therapeutic emphasis, supplementing traditional, non-specific, mechanical plaque control with a more focused targeting of pathogenic organisms . New topical preparations provide high antimicrobial doses at diseased sites without the systemic antibiotic loading which is now, in itself, a cause of concern due to the increasing tendency of micro-organisms to become resistant to antimicrobial agents . This article reviews the current methods of delivering antimicrobial agents to the gingival crevice and evaluates their roles in practical periodontal therapy.

Biochem Biophys Res Commun, 1998 Mar 6, 244(1), 253 - 7
Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions; Park CB et al.; The mechanism of action of buforin II, which is a 21-amino acid peptide with a potent antimicrobial activity against a broad range of microorganisms, was studied using fluorescein isothiocyanate (FITC)-labeled buforin II and a gel-retardation experiment . Its mechanism of action was compared with that of the well-characterized magainin 2, which has a pore-forming activity on the cell membrane . Buforin II killed Esche-richia coli without lysing the cell membrane even at 5 times minimal inhibitory concentration (MIC) at which buforin II reduced the viable cell numbers by 6 orders of magnitude . However, magainin 2 lysed the cell to death under the same condition . FITC-labeled buforin II was found to penetrate the cell membrane and accumulate inside E . coli even below its MIC, whereas FITC-labeled magainin 2 remained outside or on the cell wall even at its MIC . The gel-retardation experiment showed that buforin II bound to DNA and RNA of the cells over 20 times strongly than magainin 2 . All these results indicate that buforin II inhibits the cellular functions by binding to DNA and RNA of cells after penetrating the cell membranes, resulting in the rapid cell death, which is quite different from that of magainin 2 even though they are structurally similar: a linear amphipathic alpha-helical peptide.

J Biomol Struct Dyn, 1998 Feb, 15(4), 653 - 61
Structural features of helical aggregates of antibacterial peptides via simulated annealing and molecular modeling; Devi AS et al.; A 27-residue stretch of amino acids encompassing two putative 13-residue amphiphilic helical segments is an important determinant of activity in the 47-residue antibacterial peptide bovine seminalplasmin . Synthetic peptides corresponding to the 27-residue stretch (P27) SLSRYAKLANRLANPKLLETFLSKWIG as well as the 13-residue segments PKLLETFLSKWIG (SPF),exhibit antimicrobial activity . An analog of SPF where E has been replaced by K(SPFK) showed improved antimicrobial properties as compared to SPF . The peptides have the ability to bind and permeabilize membranes . We have modeled helical bundles of P27 and the two 13-residue peptides SPF and SPFK using simulated annealing via molecular dynamics . Octameric but not hexameric aggregates of P27 can form channels which would allow the passage of ions . In the case of 13-residue peptides, aggregates formed by 6 monomers can conceivably form ion conducting channels . Since the ability to form channels which would allow the passage of ions across the membranes is an important determinant of the biological activities of these peptides, knowledge of the pore forming structures should help in the design of analogs with improved activities.

Nihon Hansenbyo Gakkai Zasshi, 1997 Nov, 66(3), 191 - 8
{Towards new strategies to combat mycobacterial diseases}; Kobayashi K; Infectious diseases account for more than 30% of deaths throughout the world, and we are increasingly faced with new and reemerging disease challenges . Infections caused by mycobacteria are the leading cause of death from infectious diseases around the world . Leprosy/Hansen's disease, caused by Mycobacterium leprae, primarily involves the peripheral nervous system and skin . Tuberculosis remains an important global health problem with approximately 1.9 billion people presently infected with M . tuberculosis . Infections with nontuberculous mycobacteria such as M . avium complex (MAC) constitute an important health problem, because most strains of MAC are resistant to antituberculous drugs . Mycobacteria are intracellular microbial pathogens . The infect macrophages cause chronic inflammation, such as granulomatous inflammation, and progressive scarring . Host defense against mycobacterial infection is controlled predominantly by the macrophage-cytokine-type 1 helper T (Th1) cell axis resulting in the expression of cell-mediated immunity . Development of cell-mediated, Th1(1) protective immunity to mycobacteria is considered a two-edged response, contributing to both clearance of infecting agents and tissue damage . In the second half of the 20th century, the conceptual approach to the management of established infectious diseases is antimicrobial chemotherapy . However, the successful implementation of antimicrobial chemotherapy is becoming increasingly difficult because of (1) an epidemic of immunocompromised patients, for whom antimicrobial therapy is less effective; (2) the emergence of new pathogens and the reemergence of old pathogens; and (3) widespread drug resistance . Antiinfective immunotherapy will be a new control strategy for mycobacterial diseases . It is also conceivable that therapeutic interventions to enhance the host immunity will be as effective as and possibly synergistic with antimicrobial drugs . We believe that the immune-based strategies will contribute to elimination of mycobacterial diseases.

J Neurol Sci, 1998 Jan 8, 153(2), 182 - 91
Nervous system Lyme disease; Halperin JJ; Lyme disease is a multisystem infectious disease caused by tick-borne spirochetes of the Borrelia burgdorferi group . The disease occurs primarily in specific areas of North America, Europe and Asia, reflecting the distribution of the hard-shelled Ixodes ticks that are required for disease transmission . Diagnosis of this infection can be somewhat problematic, although in clinically appropriate settings, serologic testing can be highly useful, particularly if Western blots are used to confirm borderline or positive results . The organism has several specific organotropisms-involvement of the heart, joints and nervous system being particularly common . The nervous system can be involved in one or more ways . Early in infection, patients tend to get a lymphocytic meningitis, cranial neuritis (particularly the facial nerves) or a painful radiculitis . Rarely, an encephalomyelitis can occur . In patients with more protracted and indolent involvement, a more disseminated mononeuropathy multiplex may occur, or a mild, non-focal alteration of cognitive function and memory, i.e . an encephalopathy . In patients with central nervous system involvement, the most sensitive diagnostic test is the demonstration of intrathecal production of anti-Borrelia burgdorferi antibody . Culture, polymerase chain reaction and other techniques appear to be less specific . In most instances, the disease is quite responsive to antimicrobial therapy . Oral treatment with doxycycline has been shown to be effective in meningitis . In more serious cases two to four week courses of parenteral ceffriaxone or cefotaxime are effective in the vast majority of patients.

Acta Pol Pharm, 1997 Jul-Aug, 54(4), 307 - 12
A study on ester thiosemicarbazones; Ikizler AA et al.; The cyclization of ester thiosemicarbazones to two different heterocycles was studied for some new thiosemicarbazones, and only the formation of 1,2,4-triazol-5-thiols was attributed to the regioselectivity of the ring closure reaction, due to a steric hindrance of bulky groups . Next, some of the new compounds were tested for their in vitro antimicrobial and antitumor activities.

Mikrobiol Z, 1997 Nov-Dec, 59(6), 7 - 12
{The antifungal activity of new quaternary ammonium compounds and the potentials for their use in biochemical research methods}; Pishak VP et al.; Antifungal activity of quaternary ammonium compounds and possibility to use these substances as antimicrobial stabilizers was studied . Taking into consideration their ability to stabilize aqueous solutions of ascorbic acid, they can be used for a quantitative assays of total protein and bilirubin.

J Antimicrob Chemother, 1998 Jan, 41(1), 77 - 83
Antimicrobial activities of benzoxazinorifamycin KRM-1648, clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages; Sato K et al.; The in-vitro activities of KRM-1648, a new benzoxazinorifamycin, clarithromycin and levofloxacin against clinical isolates of Mycobacterium avium complex (MAC) were measured using various methods of assay and compared with their in-vivo therapeutic activities against MAC infection in mice . The MICs varied according to drug in the order KRM-1648 << clarithromycin < levofloxacin . However, KRM-1648 and clarithromycin but not levofloxacin had similar therapeutic outcomes in MAC-infected mice . KRM-1648 and clarithromycin given at clinical dosages caused 1 to 2 log unit reductions in bacterial loads in the lungs of host mice . The values of Cmax (lung)/MBC were more closely related to the therapeutic efficacy of these drugs in mice than were MICs and MBCs alone . Potent microbicidal activity was observed with KRM-1648 and clarithromycin but not with levofloxacin against extracellularly growing MAC (EG-MAC) in a liquid medium . These two agents caused more than 3 log unit killing of MAC during a 5 day incubation, when added at concentrations equivalent to Cmax (lung) . The anti-EG-MAC bactericidal activity of these drugs was greater than their efficacy in mice in vivo . KRM-1648 and clarithromycin but not levofloxacin caused respectively 2 and 0.5 log unit killing of intracellularly growing MAC (IG-MAC) in murine peritoneal macrophages . The profiles of bacterial killing effects of these agents against IG-MAC accurately reflected their therapeutic effects in mice, although the in-vivo activity of KRM-1648 was still overestimated using even this parameter.

J Antibiot (Tokyo), 1997 Dec, 50(12), 1020 - 5
Resormycin, a novel herbicidal and antifungal antibiotic produced by a strain of Streptomyces platensis . I . Taxonomy, production, isolation and biological properties; Igarashi M et al.; Resormycin, a novel herbicidal and antifungal antibiotic, was isolated from the cultured broth of streptomycete strain . The strain was isolated from a soil collected at Yokohama-shi, Kanagawa Prefecture, Japan, and identified as Streptomyces platensis MJ953-SF5 . Resormycin was purified by active charcol, Amberlite IRC-50, Amberlite CG-50 and Sephadex LH-20 column chromatographies . Resormycin markedly inhibited the growth of monocotyledonous and dicotyledonous weed . The antibiotic showed antimicrobial activity against phytopathogenic fungi.

J Immunol, 1998 Mar 15, 160(6), 2590 - 6
A physiologic role of Bcl-xL induced in activated macrophages; Okada S et al.; Activated macrophages produce nitric oxide (NO) that is an important effector molecule for their antimicrobial and antitumor activities . Since this NO is also toxic for themselves, they have self-defense mechanisms . To elucidate the mechanisms in a physiologic condition, expression of bcl-2 family genes were examined in peritoneal macrophages and RAW264 macrophage cell line activated with IFN-gamma and LPS . Bcl-xL, but not bcl-2 and bax mRNA, was highly inducible within 3 h after stimulation . The induction required new protein synthesis, but was independent of effects of synthesized NO . Since activated RAW264 were more resistant to NO-induced apoptosis mediated by the exposure to S-nitroso-N-acetyl-penicillamine (SNAP) than nonactivated RAW264, the inducible Bcl-xL may play a role in the protection from NO toxicity . To confirm the protective function, RAW264 were stably transfected with bcl-xL . Those transfectants activated with IFN-gamma and LPS appeared highly resistant to NO-induced cell death detected within 24 h after stimulation, although their NO production was similar to those of parental RAW264 and neomycin control-transfected cells . Furthermore, bcl-xL transfectants displayed substantial protection from SNAP-induced apoptosis . These results establish a link between self-defense to the synthesized NO and the induction of Bcl-xL in activated macrophages.

Infect Control Hosp Epidemiol, 1998 Feb, 19(2), 125 - 35
Hospital infection prevention and control: a model for improving the quality of hospital care in low- and middle-income countries; Huskins WC et al.; Continuous quality improvement (CQI) is a powerful methodology for improving clinical outcomes and patient satisfaction while reducing inefficiency and costs . However, most hospitals in low- and middle-income countries have little experience with CQI methods . Hospital infection prevention is an ideal model for nascent efforts to improve the quality of hospital care because of its proven efficacy in reducing the occurrence of infections that compromise patient outcomes and increase costs . This article describes the design and implementation of a demonstration project to reduce the incidence of surgical-site infections (SSIs) for hospitals with little experience with quality-improvement methods . The project has a high likelihood of producing measurable reductions in SSI rates and hospital costs related to inefficient use of perioperative antimicrobial prophylaxis . Moreover, participating staff will gain experience that can be applied to efforts to improve the quality of other aspects of hospital care.

J Ethnopharmacol, 1998 Jan, 59(3), 207 - 9
Antimicrobial activity of extracts of Mutisia acuminata var . acuminata; Catalano S et al.; The biological activity of methanol and water extracts of Mutisia acuminata Ruiz et Pavon var . acuminata (Asteraceae) against bacteria and fungi (spores and mycelia) was evaluated . The role of pH of the medium in antimicrobial activity was investigated.

J Urol, 1998 Apr, 159(4), 1224 - 8
How common is prostatitis? A national survey of physician visits; Collins MM et al.; PURPOSE: We used a national data base to explore the epidemiology of physician visits for genitourinary symptoms or a diagnosis of prostatitis . MATERIALS AND METHODS: We analyzed 58,955 visits by men 18 years old or older to office based physicians of all specialties, as included in the National Ambulatory Medical Care Surveys from 1990 to 1994 . Physicians selected by random sampling completed visit forms that included information on patient reasons for visits and physician diagnoses . RESULTS: From 1990 to 1994, 5% of all ambulatory visits by men 18 years old or older included genitourinary symptoms as a reason for the visit . In almost 2 million visits annually prostatitis was listed as a diagnosis, including 0.7 million by men 18 to 50 years old and 0.9 million by those older than 50 years . Of the prostatitis visits 46 and 47% were to urologists and primary care physicians, respectively . A prostatitis diagnosis was assigned at 8 and 1% of all urologist and primary care physician visits, respectively . The odds of a prostatitis diagnosis were 13-fold greater at visits to urologists compared with visits to primary care physicians, and approximately 2-fold greater in the south than in the northeast . Surprisingly, compared with men 66 years old or older, prostatitis was more commonly diagnosed in men 36 to 65 than men 18 to 35 years old . When a prostatitis diagnosis was given, antimicrobial use was likely to be reported 45% of the time for men with and 27% for those without genitourinary symptoms . Visits to primary care physicians were more often associated with antimicrobial use than visits to urologists . CONCLUSIONS: Genitourinary symptoms are a frequent reason for office visits by younger and older men, and prostatitis is a common diagnosis . Despite a report that less than 10% of prostatitis cases are bacterial, a much higher proportion of men in whom prostatitis is diagnosed receive antimicrobials.

Farmaco, 1997 Oct, 52(10), 639 - 43
Pyrazolo{1,5-a}pyrido{3,4-e}pyrimidin-6-ones . II . Synthesis and in vitro antimicrobial evaluation; Bruni F et al.; A series of Pyrazolo{1,5-a}pyrido{3,4-e}pyrimidin-6-ones (4a-p) was prepared by a simple synthetic procedure based on the reaction of hydroxylamine or methoxyamine with 2,3-substituted ethyl 7-dimethylaminovinyl pyrazolo{1,5-a}pyrimidin-6-carboxylates (3a-p) . The antimicrobial activity of the obtained compounds was evaluated on a series of standard strains of Gram positive, Gram negative bacteria and fungi . None of the tested compounds showed significant activity.

Farmaco, 1997 Oct, 52(10), 631 - 3
N-(chroman-4-ylidene)aryloxyacetohydrazones: synthesis and antimicrobial activity; Turan-Zitouni G et al.; In this study, some N-(chroman-4-ylidene)phenoxyacetohydrazone and N-(chroman-4-ylidene)phenoxyacetohydrazone compounds were synthesized . Structure of the compounds were identified by using IR, H NMR and MASS spectral data and by elemental analysis . Particularly, some compounds showed interesting antimycobacterial activities.

Farmaco, 1997 Aug-Sep, 52(8-9), 565 - 8
Synthesis and structure elucidation of some 4-substituted benzylidene amino-5-{3(5)-methyl-5(3)-phenyl-1H-1-pyrazolyl}-2,4-dihydro-3H-1,2,4- triazole-3-thione derivatives with their antimicrobial activities; Dogan HN et al.; A new series of 4-substituted benzylideneamino-5{3(5)-methyl-5(3)-phenyl-1H-1-pyrazolyl}-2 ,4-dihydro-3H- 1,2,4-triazole-3-thione was synthesized by reaction of I with suitable aldehyde and tested for their antimicrobial activities against six microorganisms . Most of the compounds showed antibacterial activity against Gram positive bacteria.

Vet Rec, 1998 Feb 7, 142(6), 135 - 7
Relationship between in vitro sensitivity of coliform pathogens in the udder and the outcome of treatment for clinical mastitis; Shpigel NY et al.; The relationship between in vitro sensitivity to antimicrobials and the outcome of treatment was studied in 228 cows with coliform mastitis . All the cows were treated with a preparation containing sulphonamide and trimethoprim, and 197 of them were also treated with a non-steroidal anti-inflammatory drug (NSAID) . The relationship between in vitro sensitivity to sulphonamide/trimethoprim and recovery was analysed by multivariate logistic regression . The possible confounding effects of treatment with an NSAID, days in lactation, parity, herd, and type of infecting organism were tested . Only treatment with an NSAID had a significant confounding effect and was included in the final statistical model . The recovery rate of the 165 cows infected by coliforms that were sensitive to sulphonamide/trimethoprim (89.1 per cent) was higher than that of the 63 cows infected by coliforms that were resistant to sulphonamide/trimethoprim (74.6 per cent) . The odds ratio of recovery for the cases associated with organisms that were sensitive to sulphonamide/trimethoprim relative to the cases associated with organisms that were resistant to sulphonamide/trimethoprim was 2.75, with a 95 per cent confidence from 1.25 to 5.85 . The odds ratio of recovery for the cases treated with an NSAID relative to the cases treated with sulphonamide/trimethoprim only was 2.76 with a 95 per cent confidence interval from 1.12 to 6.79.

Trends Microbiol, 1998 Feb, 6(2), 54 - 61
Engineering disease and pest resistance in plants; Dempsey DA et al.; Improvements in transformation techniques and the isolation of many genes whose transcripts or protein products either have antimicrobial or insecticidal activity or are involved in the synthesis of products with such activities have provided valuable tools for engineering resistance in plants . Future exploitation of this technology should provide an environmentally friendly alternative to traditional disease and pest control measures.

J Vet Pharmacol Ther, 1998 Feb, 21(1), 18 - 23
Concentration of enrofloxacin and its active metabolite in alveolar macrophages and pulmonary epithelial lining fluid of dogs; Hawkins EC et al.; The purpose of this study was to determine the concentration of enrofloxacin and its active metabolite, ciprofloxacin, in alveolar macrophages (AM) and epithelial lining fluid (ELF) of the lungs in comparison to plasma concentrations in healthy dogs . Eleven dogs were given a single oral dose (5 mg/kg) of enrofloxacin . Four hours later, plasma and bronchoalveolar lavage (BAL) fluid were collected . Cells were separated from the BAL fluid and lysed for determination of drug concentrations within AM . Supernatant was used to determine concentrations of drugs in ELF . Drug assays were performed by high-performance liquid chromatography . The concentration of enrofloxacin (mean +/- SD) was 0.33 +/- 0.14 microgram/mL in plasma, 3.34 +/- 2.4 micrograms/mL in AM and 4.79 +/- 5.0 micrograms/mL in ELF . The concentration of ciprofloxacin was 0.42 +/- 0.26 microgram/mL in plasma, 1.15 +/- 1.03 micrograms/mL in AM and 0.26 +/- 0.26 microgram/mL in ELF . Mean concentrations of both drugs in AM were greater than in plasma (AM to plasma ratio, 10.3 for enrofloxacin and 4.7 for ciprofloxacin) . Mean concentrations of enrofloxacin, but not ciprofloxacin, in ELF were greater than in plasma (ELF to plasma ratio, 13.5 for enrofloxacin and 0.52 for ciprofloxacin) . Enrofloxacin concentrations in AM and ELF largely exceeded the MICs of the major bacterial pathogens and surpassed by about two times the breakpoint MIC of that drug, and ciprofloxacin concentrations in AM surpassed the MIC of many susceptible organisms . These results suggest that sufficient antimicrobial activity is present in AM and ELF of dogs following oral administration of enrofloxacin to be effective in the treatment of lower respiratory tract infections involving susceptible organisms.

Eur J Pediatr, 1998 Feb, 157(2), 107 - 8
Anti-thymocyte globulin, cyclosporin A and granulocyte colony-stimulating factor for severe aplastic anaemia complicating paediatric liver transplantation; Hadzic N et al.; We describe a sustained trilineage haematopoietic response to intensified immunosuppressive therapy with anti-thymocyte globulin, cyclosporin A and recombinant human granulocyte colony-stimulating factor in a 4-year-old girl, who developed severe aplastic anaemia after orthotopic liver transplantation for fulminant liver failure induced by non A-E hepatitis . The outcome was successful and allows the following . CONCLUSION: Intense immunosuppression in combination with haemopoetic growth factors and antimicrobial prophylaxis should be considered as first line therapy in severe aplastic anaemia after orthotopic liver trans-plantation.

J Biochem (Tokyo), 1998 Jan, 123(1), 1 - 15
New types of clotting factors and defense molecules found in horseshoe crab hemolymph: their structures and functions; Iwanaga S et al.; Invertebrate animals, which lack adaptive immune systems, have developed defense systems, so-called innate immunity, that respond to common antigens on the surface of potential pathogens . One such defense system is involved in the cellular responses of horseshoe crab hemocytes to invaders . Hemocytes contain two types, large (L) and small (S), of secretory granules, and the contents of these granules are released in response to invading microbes via exocytosis . Recent biochemical and immunological studies on the granular components of L- and S-granules demonstrated that the two types of granules selectively store granule-specific proteins participating in the host defense systems . L-Granules contain all the clotting factors essential for hemolymph coagulation, protease inhibitors including serpins and cystatin, and anti-lipopolysaccharide (LPS) factor and several tachylectins with LPS binding and bacterial agglutinating activities . On the other hand, S-granules contain various new cysteine-rich basic proteins with antimicrobial or bacterial agglutinating activities, such as tachyplesins, big defensin, tachycitin, and tachystatins . The co-localization of these proteins in the granules and their release into the hemolymph suggest that they serve synergistically to construct an effective host defense system against invaders . Here, the structures and functions of these new types of defense molecules found in the Japanese horseshoe crab (Tachypleus tridentatus) are reviewed.

Kansenshogaku Zasshi, 1998 Jan, 72(1), 54 - 9
{Clinical study on sparfloxacin (SPFX) in the treatment of mycoplasmal pneumonia and penetration of SPFX to the pneumonic lesion}; Hayashi Y et al.; We treated nine patients of mycoplasmal pneumonia with sparfloxacin (SPFX) the clinical efficacy, safety and usefulness of SPFX were evaluated . SPFX was administered orally at doses of 200 or 300 mg once daily, and we performed bronchoalveolar lavage (BAL) examinations in five patients . BAL was performed 5 hours after oral administration of 100 mg in one case, 19 hours after oral administration of 200 mg in four cases . Concentrations of SPFX and alubumine were measured in serum and in BALF (bronchoalveolar lavage fluid) . The following results were obtained . 1 . Nine patients were evaluated; eight patients judged as Good, one patient as Excellent . 2 . The serum and BALF levels of SPFX was 0.79 microgram/ml, 0.107 microgram/ml 5 hours after single oral administration of 100 mg in one case and 19 hours after oral administration of 200 mg in four cases, those of levels of SPFX were 0.835 +/- 0.274 microgram/ml and 0.081 +/- 0.033 microgram/ml, respectively . 3 . The ratio of SPFX/albumin in BALF was significantly higher than in the serum . From these results, we consider that SPFX is a useful antimicrobial agent for mycoplasmal pneumonia.

Nippon Yakurigaku Zasshi, 1997 Oct, 110 Suppl 1, 199P - 204P
{Effect of discodermin A, an antimicrobial peptide, on the cytoplasm membrane}; Sato K et al.; The effects of discodermin A, an antimicrobial peptide extracted from sea sponge Discodermia kiiensis, on cell membranes were investigated using vascular smooth muscle cells and erythrocytes . At lower concentrations (0.1-3 microM), discodermin A increased muscle tension with an increase in intracellular free Ca2+ concentration ({Ca2+}i) indicated by the fluorescence of Ca2+ indicator, fura-PE3, in rat aortic smooth muscle . On the other hand, the higher concentration of discodermin A (10-30 microM) accelerated the leakage of loaded fura-PE3 from cells . In rabbit mesenteric artery treaded with discodermin A, addition of micromolar concentration of Ca2+ evoked contraction in the presence of ATP, suggesting that permeability of the membrane to Ca2+ and ATP is increased by discodermin A . Confocal fluorescence microscopy showed that discodermin A permeabilized the plasma membrane of A10 cells to fluorescent agents EthD-1 and the intracellular esterase coupled with another fluorescent agent calcein . Discodermin A also showed a hemolytic effect on rabbit erythrocytes, suggesting that discodermin A permitted transmembrane passage of hemoglobin . These results suggest that discodermin A form pores of different sizes on the cytoplasm membrane in concentration- and time-dependent manners . Discodermin A may be a saponin-like bioactive peptide.

Clin Infect Dis, 1998 Feb, 26(2), 359 - 64
Acute glomerulonephritis associated with acute Q fever: case report and review of the renal complications of Coxiella burnetii infection; Korman TM et al.; We report a case of acute glomerulonephritis associated with acute Q fever . An abattoir worker with a nonspecific febrile illness and pneumonia and abnormal liver function test results developed hematuria, proteinuria, and acute renal failure that resolved with appropriate antimicrobial therapy . Renal biopsy demonstrated diffuse proliferative and exudative glomerulonephritis . Serological tests confirmed recent infection with Coxiella burnetii, with a fourfold rise in the titer of phase II antibody, positive phase II IgM antibody, and negative phase I antibody . Other known causes of glomerulonephritis were excluded . Most reports of renal complications of C . burnetii infection describe glomerulonephritis associated with endocarditis due to chronic Q fever . Renal involvement in patients with acute C . burnetii infection has been rarely described . Glomerulonephritis should be recognized as a complication of acute C . burnetii infection and endocarditis due to chronic Q fever.

Rev Sci Tech, 1997 Aug, 16(2), 709 - 15
Therapeutic antibiotics in animal feeds and antibiotic resistance; Tollefson L et al.; Recent statutory changes involving animal drugs are expected to facilitate the therapeutic use of antibiotics in animal feeds in the United States of America . The use of antibiotics in animal feeds is controversial due to the potential development of resistant bacterial pathogens in food-producing animals which are exposed to the antibiotics and the resultant public health risk . Zoonotic micro-organisms can be transmitted to humans through contact with animal populations, either directly or through the consumption of contaminated food . Recommendations to address the public health concerns include the strengthening of professional education in the areas of infectious diseases and the appropriate selection and use of antimicrobial agents, the development of a comprehensive food safety education programme for food-animal veterinarians and animal producers, and the development of surveillance programmes to monitor antimicrobial resistance among zoonotic pathogens . Early identification of emerging resistance can facilitate a timely and appropriate public health response.

Rev Sci Tech, 1997 Aug, 16(2), 694 - 708
Problems associated with drug residues in beef from feeds and therapy; Kaneene JB et al.; Drug residues in beef have been reported internationally . These include antimicrobials, anti-inflammatories, growth promotants, parasiticides and insecticides . The main factors associated with residues are animal age and use, and failure to observe withdrawal time for regular or extra-label use . Public health concerns include toxic and anaphylactic reactions, and development of drug-resistant strains of bacteria . The maximum residue level (MRL) is the current standard for residues in food adopted by the Codex Committees of the Food and Agriculture Organisation and World Health Organisation, but is not universally accepted or standardised . Detection of residues at slaughter is a critical point in residue control . Several live animal tests are available, but these vary in reliability and usage . After slaughter, tissues sampled and tests used are more uniform . To prevent international trade barriers associated with drug residues in beef, the following conditions should be implemented: standardisation of testing methods used to detect drug residues; standardisation of methods for determining MRLs; establishment of active surveillance programmes to monitor residues.

Plast Reconstr Surg, 1998 Mar, 101(3), 756 - 65
Enhanced proliferation of fibroblasts and endothelial cells treated with an extract of the leaves of Chromolaena odorata (Eupolin), an herbal remedy for treating wounds; Phan TT et al.; Burns are a major problem in many developing countries . Eupolin ointment is a topical agent used in the treatment of soft-tissue wounds and burns in Vietnam and is made from an aqueous extract of the leaves of Chromolaena odorata (formerly Eupatorium odoratum) . Clinical studies using this extract have shown antimicrobial and anticoagulation effects as well as the promotion of tissue remodeling in the wound healing process . However, the mechanism by which this agent affects cells involved in the wound healing process is unknown . In our research, fibroblasts and endothelial cells, two cell types that play a crucial role in wound healing, were used to investigate some of the effects of Eupolin extract in vitro . Cell growth was estimated by a colorimetric assay at different time intervals . Enhanced growth of fibroblasts and endothelial cells was found at concentrations of 10 microg/ml and 100 microg/ml of Eupolin extract . This was particularly evident in medium supplemented with only 0.5% fetal calf serum where the cells were quiescent . Toxicity of the extract to fibroblasts was observed at 250 microg/ml in Dulbecco's modified Eagle's medium/0.5% fetal calf serum, but there was no significant damage at this dose to the endothelial cells . The results of the study demonstrated that Eupolin extract increased fibroblast and endothelial cell growth, and this could explain in part the beneficial clinical effects that have been observed.

J Nutr, 1998 Feb, 128(2 Suppl), 297S - 299S
Antimicrobial peptide expression is developmentally regulated in the ovine gastrointestinal tract; Huttner KM et al.; Antimicrobial peptides are abundant components of the innate immune system present in species throughout the plant and animal kingdoms . In mammals, these immune peptides have been localized to epithelial tissues of the pig, mouse, rat, cow and human gastrointestinal tracts . We have identified in sheep two members of the beta-defensin antimicrobial peptide gene family that are expressed in a unique pattern throughout the gastrointestinal tract . Sheep beta-defensin 1 mRNA is the most prevalent from tongue to colon with the exception of the distal ileum, where beta-defensin 2 mRNA predominates . Sheep beta-defensin expression varies significantly between animals and is developmentally regulated both pre- and postnatally . These changes in antimicrobial peptide expression may correlate with anatomical differentiation as well as physiologic adaptations to extra-uterine life.

FASEB J, 1998 Mar, 12(3), 265 - 74
Evolutionary origins of multidrug and drug-specific efflux pumps in bacteria; Saier MH Jr et al.; The available genomic sequences of three pathogenic and three nonpathogenic bacteria were analyzed to identify known and putative drug-specific and multidrug resistance transport systems . Escherichia coli was found to encode 29 such pumps, and with the exception of the archaebacterium Methanococcus jannaschii, the numbers of multidrug efflux pumps encoded within genomes of the other organisms were found to be approximately proportional to their total numbers of encoded transport systems as well as to total genome size . The similar numbers of chromosomally encoded multidrug efflux systems in pathogens and nonpathogens suggests that these transporters have not arisen recently in pathogens in response to antimicrobial chemotherapy . Phylogenetic analyses of the four transporter families that contain drug efflux permeases indicate that drug resistance arose rarely during the evolution of each family and that the diversity of current drug efflux pumps within each family arose from just one or a very few primordial systems . However, although the ability to confer drug efflux appears to have emerged on only a few occasions in evolutionary time and was stably maintained as an evolutionary trait, modulation of the substrate specificities of these systems has occurred repeatedly . A speculative model is presented that may explain the apparent capability of these multidrug transport systems to mediate drug transport from the cytoplasm or directly from the phospholipid bilayer.

J Clin Pharmacol, 1997 Dec, 37(12), 1108 - 13
Relationship between serum and free interstitial concentrations of cefodizime and cefpirome in muscle and subcutaneous adipose tissue of healthy volunteers measured by microdialysis; Muller M et al.; Microdialysis is a suitable method to monitor unbound concentrations of antimicrobial drugs in the interstitial tissue space which is the site of many infections . The aim of this investigation was to examine whether free tissue levels of cefodizime (81% plasma protein binding) and cefpirome (10% plasma protein binding) in muscle and subcutaneous adipose tissue of healthy volunteers obtained by microdialysis are consistent with the extent of their respective plasma protein binding . Healthy volunteers were given cefodizine and cefpirome at a single intravenous 2-g dose in a randomized crossover design . Microdialysis probes were inserted into a medial vastus muscle and into the periumbilical subcutaneous layer . After calibration of the probe, samples of serum and microdialysis fluid were obtained and drug concentrations were measured using a microagar diffusion-bioassay . There was a reasonable agreement between plasma protein binding data and the tissue penetration of both cephalosporins (AUC0-infinity tissue, free/AUC0-infinity serum, total-ratios) into the interstitial fluid of the muscle tissue, but not for the subcutaneous tissue layer . Furthermore, the serum and tissue concentrations of both drugs were fitted to an open two-compartment body model . The measured free-tissue concentrations were compared with calculated unbound concentrations in the peripheral compartment . Good agreement was observed for the free muscle concentrations, but unbound concentrations in the subcutaneous tissue was somewhat higher (cefpirome) or lower (cefodizime) than predicted . This may be due to the different lipophilicities of the two compounds.

Infection, 1998 Jan-Feb, 26(1), 26 - 31
Causes of the antimicrobial activity of honey; Wahdan HA; The present study was performed to clarify the possible causes of the antimicrobial activity of honey . A sugar solution resembling honey in its high sugar content was made . The antimicrobial activities of both honey and this solution towards 21 types of bacteria and two types of fungi were examined . The results achieved by both were compared . The difference between them indicated the presence of antimicrobial substance(s) in honey . The kinds of antimicrobial substances (inhibines) in honey are discussed . Hydrogen peroxide is not the only inhibine in honey . In fact, inhibines in honey include many other substances . Two important classes of these inhibines are the flavonoids and the phenolic acids . Flavonoids have often been extracted from honey previously . In this study two phenolic acids (caffeic acid and ferulic acid) were extracted from honey for the first time.

Protein Expr Purif, 1998 Feb, 12(1), 53 - 60
Acidic peptide-mediated expression of the antimicrobial peptide buforin II as tandem repeats in Escherichia coli; Lee JH et al.; Antimicrobial peptides have received increasing attention as a new pharmaceutical substance, because of their broad spectrum of antimicrobial activities and the rapid development of multidrug-resistant pathogenic microorganisms . The main obstacle to the wide application of antimicrobial peptides has been the lack of a cost-effective, mass-production method . A novel mass-production method for an antimicrobial peptide of 21 amino acids, buforin II, which was isolated from the stomach of the amphibian Bufo bufo gargarizans, has been developed . This method is based on the neutralization of the positive charges of buforin II by fusing to an acidic peptide to avoid the lethal effect of the expressed antimicrobial peptide on the host cells . The fusion peptide was expressed in Escherichia coli as tandem repeats to increase the product yield . Multimers of the acidic peptide-buforin II fusion peptide were expressed at high levels without causing damage to the cells . The presence of cysteine residues in the acidic peptide was critical for the high level expression of the fusion peptide multimers . Multimers of this fusion peptide were expressed as inclusion bodies, and about 107 mg of pure buforin II was obtained from 1 L of E . coli culture by cleaving the multimers with CNBr . Recombinant buforin II had an antimicrobial activity identical to that of natural buforin II . These results may lead to a general, cost-effective solution to the mass production of antimicrobial peptides and other basic peptides which are lethal to the host strain .

Ann Pharmacother, 1998 Feb, 32(2), 189 - 92
Trimethoprim/sulfamethoxazole-induced tremor in a patient with AIDS; Slavik RS et al.; OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced tremor responsive to a reduction in dosage . CASE SUMMARY: A 55-year-old white man with AIDS and Pneumocystis carinii pneumonia (PCP) developed a tremor after receiving 5 days of therapy with TMP/SMX 19.4 mg/kg/d (TMP) . The tremor resolved completely 3 days after a dosage reduction to TMP/SMX 15.1 mg/kg/d . DISCUSSION: Central nervous system adverse reactions to TMP/SMX have been reported in both the AIDS and non-AIDS populations . To our knowledge, this is the first reported case of TMP/SMX-induced tremor responsive to a reduction in dosage . Pharmacokinetic and clinical data suggest a concentration-dependent etiology for various adverse effects, including tremor . The mechanism of the tremor is unknown; however, toxic metabolites of SMX and disruptions of biogenic amine neurotransmission by TMP have been hypothesized . CONCLUSIONS: TMP/SMX remains the drug of first choice for treating PCP, but it is clearly not well tolerated by patients with AIDS . Concentration-dependent toxicities such as tremor may lead to premature discontinuation of proven, effective TMP/SMX therapy . Using the lower end of the recommended dosing range for TMP/SMX (TMP 15 mg/kg/d) may reduce the incidence of these toxicities while still achieving acceptable TMP concentrations and antimicrobial efficacy.

Eur J Clin Microbiol Infect Dis, 1997 Dec, 16(12), 904 - 12
Implementation of an educational program and an antibiotic order form to optimize quality of antimicrobial drug use in a department of internal medicine; Gyssens IC et al.; In a study designed to evaluate the effects of an educational program and an antibiotic order form on the quality of antimicrobial drug use, a prospective analysis was conducted in the department of internal medicine of a 948-bed university hospital . Following a quality-of-use review of all consecutive courses of antimicrobial drugs prescribed during four weeks, an educational program was conducted and an antibiotic order form introduced . After four years, an identical review was performed . In the first review, 109 (31%) of 347 patients were prescribed antimicrobial drugs . Only 40% of the prescriptions were considered definitely appropriate, and 13% were considered unjustified . There was a certain degree of underutilization, and only 67% of clinical isolates were susceptible to empirical therapy . In the review performed after intervention, 164 (21%) of 796 patients were given antimicrobial drugs . Defined daily doses per 100 bed days increased from 59.8 to 72.6 . Fifty-three percent of the prescriptions were judged optimal, and only 9% were judged unjustified . Ninety percent of the clinical isolates were susceptible to empirical therapy . After one year, compliance with the antibiotic order forms on a voluntary basis reached 77%, documenting 86% of antimicrobial drug costs . As a result, the antibiotic order form will be useful for surveillance, if logistic support is provided by the pharmacy . The combination of several measures leads to improved quality of use . As correctly predicted by the first evaluation, improvement in quality resulted in increased drug consumption by fewer patients and a higher cost per bed day.

FEMS Microbiol Lett, 1998 Mar 1, 160(1), 91 - 6
Mechanism of antimicrobial action of indolicidin; Subbalakshmi C et al.; Indolicidin, a 13-residue antimicrobial peptide isolated from cytoplasmic granules of bovine neutrophils, exhibits activity against Gram-positive and Gram-negative bacteria as well as fungi . Although indolicidin is bactericidal and permeabilizes the bacterial membranes, it does not lyse the bacterial cells . We examined the effect of bactericidal concentrations of indolicidin on the morphology of Escherichia coli cells and found that it induces filamentation . Further investigations showed that indolicidin inhibits DNA synthesis in E . coli cells at concentrations at which RNA and protein synthesis are either partially affected or not affected at all . Since inhibition of DNA synthesis is also known to induce filamentation in E . coli, it appears to contribute to the antimicrobial activity of indolicidin.

Ann Acad Med Singapore, 1997 Sep, 26(5), 687 - 90
Orthopaedic implant infections: current management strategies; Allen DM; Orthopaedic joint replacement and spinal stabilisation surgery has provided pain relief and functional improvement for millions . Postoperative infections involving the implanted hardware can have devastating functional, emotional and financial consequences . Implementation of relevant preoperative patient preparation, utilisation of appropriate prophylactic antimicrobials and intraoperative infection control measures have combined to diminish orthopaedic implant infection frequency significantly . Our adeptness at establishing the presence of an implant-related infection with certainty is not as well advanced . Similarly, treatment guidelines, while useful, remain somewhat anecdotal . The pathogenesis, risk factors, diagnosis, management and prevention of hip arthroplasty infection and spinal stabilisation with instrumentation infection are reviewed.

Anticancer Res, 1997 Nov-Dec, 17(6D), 4339 - 44
Role of chemotherapeutic antagonism in opportunistic infections; Castelli M et al.; The most widely-known anti-tumor drugs often induce marked immunosuppression which can give rise to one or more sepses . Anti-infection measures immediately applied can sometimes prove largely ineffective or even useless, the patient dying not as a result of the spread of the tumour but as a direct consequence of opportunistic infection . We postulate that antagonism between anti-tumour and antimicrobial drugs may also play an important part in this . By way of illustration of this hypothesis, we have studied the action of a number of known inhibitors of peptidoglycan synthesis and of DNA-gyrases on certain strains of Gram-positive and Gram-negative microorganisms cultured in medium containing various concentrations of some of the best-known anti-tumour antimetabolites . The experimental data show that antimicrobial and anti-tumour drugs can sometimes induce synergic or indifferent chemotherapeutic interactions with many bacteria, while in others the effect is antagonistic . In practice, the action of the drugs could lead to bacterial selectivity, which, in conjunction with immunosuppression and the presence of resistant strains, could favour the evolution of opportunistic infection.

Ann Allergy Asthma Immunol, 1998 Feb, 80(2), 185 - 8
Detection of patients with multiple drug allergy syndrome by elective tolerance tests; Asero R; BACKGROUND: Multiple drug allergy syndrome (MDAS) caused by antibiotics is frequently observed in allergy departments; however, risk factors for such a condition as well as the means to detect patients prone to MDAS are poorly defined . OBJECTIVE: The identification of patients prone to MDAS and the detection of risk factors for multiple antibiotic sensitivity . METHODS: Two hundred fifty-three elective oral challenges with alternative antimicrobial drugs were performed in 120 patients with histories of recent allergic reactions to antibiotics . RESULTS: Twenty-three (19%) subjects reacted to at least one antibiotic class . All reactions were mild and easily controlled by conventional therapy . Female sex, history of multiple antibiotic reactions, and reactions to nonsteroidal antinflammatory drugs were the main risk factors for reactions to alternative antibiotics . To date, no patient has reported immediate adverse reactions to drugs negative on oral challenge tests but one had urticaria/angioedema on the fifth day of full dose treatment with ofloxacin . CONCLUSIONS: Elective oral challenges with alternative antibiotics are a sensitive, specific, and safe means to detect patients with MDAS, thus sparing them more severe adverse reactions caused by full dose therapies . The recommendation to perform oral challenge tests with antibiotics just before their therapeutic use seems unnecessary and should be reconsidered.

Pediatr Infect Dis J, 1998 Feb, 17(2), 135 - 42
Sepsis during total parenteral nutrition: exploration of risk factors and determination of the effectiveness of peripherally inserted central venous catheters; Yeung CY et al.; BACKGROUND: Sepsis is the most frequent serious complication during total parenteral nutrition (TPN), resulting in increased morbidity, mortality and health care costs . Existing reports have not documented the risk factors of sepsis during TPN . The objectives of this study were to determine the rate of sepsis in our practice and to explore the risk factors for sepsis during TPN . We also determined the role and efficacy of using peripherally inserted central venous catheters (PCVC) as insertion catheters to administer TPN . METHODS: From October, 1994, to May, 1996, we administered TPN to 378 pediatric patients hospitalized at Mackay Memorial Hospital . We followed all cases for the occurrences of any complications while administering TPN . We studied all patients who had fever, a clinical presentation of sepsis and a positive blood culture during their course of TPN . RESULTS: During the 20-month period 378 patients received TPN for a total of 6562 days . Fifty-six patients presented with clinical sepsis and positive blood cultures . Significant features in the sepsis group included longer duration of TPN, age < 3 months, usage of central venous catheters, gastrointestinal diseases as indication for TPN, low birth weight and short gestational age in prematurity . Seven patients died despite prompt antimicrobial therapy . One hundred eleven patients received TPN via PCVC for a mean duration of 17.1 days, significantly longer than 10.4 days in the peripheral intravenous catheter group but no difference between the sepsis rates . CONCLUSION: Considering the high incidence of sepsis during TPN, every attempt should be made to minimize the length of TPN therapy and encourage early enteral feeding . We also recommend the use of PCVC in patients requiring prolonged nutritional support.

Am J Vet Res, 1998 Feb, 59(2), 138 - 42
Antimicrobial susceptibility patterns of fungi isolated from horses with ulcerative keratomycosis; Brooks DE et al.; OBJECTIVES: To evaluate in vitro susceptibility to topical antifungal medications, as measured by minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50%), of fungal isolates from horses with ulcerative keratomycosis in Florida; to compare results with those of other studies to identify differences in susceptibility patterns among fungi isolated from horses in different geographic regions; and to note indications of fungal resistance to drugs tested in other studies . SAMPLE POPULATION: Corneal fungal cultures from client-owned horses from Florida with ulcerative keratomycosis (n = 22) . PROCEDURE: Fungal cultures were plated on Emmons modified Sabouraud dextrose agar and mycobiotic agar, examined weekly for growth, and kept for a total of 30 days . In vitro MIC and IC50% of fluconazole, itraconazole, ketoconazole, miconazole, and natamycin were measured for each fungal isolate . RESULTS: Aspergillus (n = 9; 41%), Fusarium (7; 32%), Penicillium (2; 9%), Cylindrocarpon (1; 4%), Scytalidium (1; 4%), and Torulopsis (1; 4%) spp and an unidentified yeast (1; 4%) were isolated . Fungi were most susceptible to antifungal drugs in the following order: natamycin and miconazole equally, itraconazole, and ketoconazole, although no significant difference was found among drugs . Fungi were significantly less susceptible to fluconazole (P < 0.0001) than to the other 4 drugs . CONCLUSIONS: Initial antifungal therapy with topically applied natamycin, miconazole, itraconazole, or ketoconazole is recommended for ulcerative keratomycosis in horses in the subtropical environment of Florida . CLINICAL RELEVANCE: Specific antifungal treatment of horses with ulcerative keratomycosis should be based on history, results of ophthalmic examination, cytologic findings, isolation of the pathogenic fungus, and known prevalence of unique ocular fungi in specific geographic areas . In vitro antifungal susceptibility testing may be most beneficial in aiding documentation of pharmacologic susceptibility patterns of fungi in specific geographic regions.

Rinsho Byori, 1998 Jan, 46(1), 9 - 14
{Alteration of genomic structure and/or expression of cancer associated genes in hepatocellular carcinoma}; Fujimoto Y et al.; Cancer is thought to arise from the accumulation of several genetic mutations in a single cell . These include integration of viral genomes, activation of protooncogenes and inactivation of tumor suppressor genes . HCC is one of the most common cancers in Asia and Africa . Various studies have revealed its association with hepatitis B or C viral infection . While activation of known protooncogenes, such as ras genes does not seem to play an important role, frequent allelic loss on specific chromosomal arms, 4q, 13q, 16q and 17p, indicates that dysfunction of diverse tumor suppressor genes located on these chromosome arms is involved in the development of HCC . An informative p53 mutational spectrum of frequent G to T transversions in codon 249 is found in HCCs from either Qidong, People's Republic of China, or southern Africa . This observation links exposure to aflatoxin B1, a known cancer risk factor in these geographic regions . Recently, we found that expression of syndecan-1, which is a transmembrane heparan sulfate proteoglycan involved in cell matrix interactions and growth factor bindings, was inversely associated with metastatic potential in human hepatocellular carcinoma as like nm23-H1 expression was . Transfection with syndecan-1 gene suppresses invasive activity of hepatoma cells . These data support our hypothesis that syndecan-1 is one of important metastasis suppressor factors in hepatoma cells . PR-39 is a proline-rich antimicrobial peptide which was isolated from a pig small intestine and has been reported to induced syndecan-1 on mouse mesenchymal cells . Transfection with PR-39 gene caused induction of syndecan-1 and altered invasive phenotype and actin structure on hepatoma cells . Syndecan-1 and PR-39 may serve as a basis for design of drug or gene therapy effective against metastasis of hepatocellular carcinomas.

Vet Rec, 1998 Jan 24, 142(4), 83 - 5
Serum haptoglobin concentrations in Holstein dairy cattle with toxic puerperal metritis; Smith BI et al.; The serum concentration of haptoglobin was measured in 51 cows with toxic puerperal metritis which were being treated with one of three different antimicrobial regimens . The mean concentration of haptoglobin was 19.0 mg/dl on the day that the treatments began and declined steadily during the five day treatment period to a mean concentration of 7.35 mg/dl . There was no correlation between the serum haptoglobin concentrations and the rectal temperatures of the cows during the five days.

Ann Nutr Metab, 1997, 41(6), 371 - 5
Antimicrobial functions of human monocytes depend on concentration of glutamine in vitro; Ruggeberg J et al.; We investigated the impact of different concentrations of glycyl glutamine on antimicrobial functions of human monocytes in vitro . Generation of suproxide anion, phagocytosis and killing capacity were measured as an expression of antimicrobial activity after an incubation period of 38 h at glycyl glutamine concentrations of 0.0, 0.4, and 2.0 mmol/l respectively . For each of the tests, significantly higher results were obtained with concentrations of glycyl glutamine of 0.4 mmol/l as compared to 0.0 mmol/l (p < 0.01) . Further increases of superoxide anion production (p < 0.05) and killing capacity (p = 0.053) were observed when glycyl glutamine concentration in the culture medium was raised to 2.0 mmol/l . Variation of glycyl glutamine concentrations in vitro significantly affects antimicrobial functions of human monocytes.

Lijec Vjesn, 1997 Mar-Apr, 119(3-4), 109 - 12
{Rapid differentiation between bacterial and atypical pneumonia in children}; Benic B et al.; We examined 116 children aged 3-7 years who were hospitalized in our Clinic during the period of one year . We observed certain clinical and laboratory parameters connected with chest X-rays . These parameters were necessary for fast distinguishing between bacterial and atypical pneumonia, in order to initiate an adequate antimicrobial therapy . The most important laboratory parameter for a fast diagnosis is CRP (reactant of acute phase of inflammation, which increases as soon as 6 to 12 hours from the beginning of the illness), and also important is: leukocyte count together with neutrophilia in differential count, which is also shown in our article . Erythrocyte sedimentation rate was moderately elevated in both bacterial and atypical pneumonia . However, the values were moderately higher in cases of bacterial pneumonia, especially in children who were hospitalized between the 2nd and the 5th day of the illness . Nevertheless, there was no correlation between the erythrocyte sedimentation rate and the type of the illness in children who were hospitalized on the first day of the illness . We conclude that CRP was the most useful parameter in fast distinguishing bacterial from atypical pneumonia.

FEBS Lett, 1998 Jan 30, 422(2), 205 - 8
Structures involved in the interaction of Porphyromonas gingivalis fimbriae and human lactoferrin; Sojar HT et al.; The ability of laboratory and clinical strains of Porphyromonas gingivalis to bind lactoferrin has been assessed (FEMS Immunology and Medical Microbiology, 1996, 14, 135-143) . Relative binding for P . gingivalis to lactoferrin varies among strains from 3.78 to 26.62% . We also observed that fimbriated strains of P . gingivalis bind more strongly to lactoferrin as compared to nonfimbriated strains of P . gingivalis . This observation led us to study fimbrial interaction with human lactoferrin and the fine structure of these interactions . Binding of iodinated purified fimbriae was studied using an overlay assay . Iodinated fimbriae bind specifically and strongly to human lactoferrin . When various sugars were used to inhibit binding, only N-acetylgalactosamine and fucose were inhibitory . To confirm further that oligosaccharide of lactoferrin is involved in the interaction, lactoferrin was chemically deglycosylated, and fimbriae failed to bind deglycosylated lactoferrin . Antifimbriae, as well as four antipeptide antibodies against different regions of the P . gingivalis fimbrillin, were used to inhibit the interaction . Antipeptide E, directed against amino acids 81-98 (AAGLIMTAEPKTIVLKAG-C), was found to be the most effective inhibitor for the lactoferrin-fimbriae interaction . These results suggest that the binding of P . gingivalis cells to lactoferrin is lectin like, directed to a oligosaccharide of lactoferrin . Furthermore, these studies suggest that the region of fimbriae that binds to lactoferrin is the N-terminus of the molecule . It is likely that binding of lactoferrin to P . gingivalis cells results in antimicrobial activity directed against these cells by virtue of its ability to deprive the bacterial cell of needed iron.

Lett Appl Microbiol, 1998 Jan, 26(1), 61 - 3
Antimicrobial effects of aqueous plant extracts on the fungi Microsporum canis and Trichophyton rubrum and on three bacterial species; Maoz M et al.; Aqueous extracts of 10 plants were tested for their ability to inhibit Trichophyton rubrum and Microsporum canis, the aetiological agents of dermal fungal infections in humans . These extracts were also evaluated for their activity against some bacteria . Aqueous extracts from the leaves of Inula viscosa produced detectable antifungal activity against these dermatophytes.

Br J Hosp Med, 1997 Sep 3-16, 58(5), 217 - 20
Coping with nosocomial infection: a non-antibiotic approach; Jones SG et al.; This article discusses the control of nosocomial infection using strategies other than antimicrobial therapy, based on the concepts of asepsis, disinfection and isolation of infectious patients . The aim is to prevent the spread of pathogenic organisms from patient to patient . Infection control techniques are practised in parallel with direct antibiotic therapy but should reduce the overall use of antibiotics, and reduce the selection pressure for organisms to develop resistance.

Neurol Clin, 1997 Nov, 15(4), 903 - 25
Vasculitis owing to infection; Gerber O et al.; Infections are a recognized cause of secondary vasculitis . A variety of pathogens have a propensity to involve blood vessels . Vasculitis, non-vasculitic vasculopathy, and mycotic aneurysms lead to infarction and hemorrhage of nervous system tissue . Treatment of infection-related vasculitis should include appropriate antimicrobial therapy directed against the offending pathogen, and appropriate management of cerebrovascular complications.

Infect Immun, 1998 Mar, 66(3), 1225 - 32
Mouse beta-defensin 1 is a salt-sensitive antimicrobial peptide present in epithelia of the lung and urogenital tract; Bals R et al.; One component of host defense at mucosal surfaces appears to be epithelium-derived peptides with antimicrobial activity called defensins . Human beta-defensin 1 (hBD-1) represents the first member of the beta-defensin family isolated from humans and has been implicated in the pathogenesis of cystic fibrosis . We describe in this report the isolation and characterization of a murine homolog of hBD-1 called mouse beta-defensin 1 (mBD-1) . The predicted amino acid sequence shows the hallmark features of other known epithelial beta-defensins, including the ordered array of six cysteine residues . Analysis of a genomic clone of mBD-1 revealed two exons separated by a 15-kb intron . By use of fluorescence in situ hybridization, the mBD-1 gene was localized at the proximal portion of chromosome 8, the site where mouse alpha-defensins are found . Lysates from cells transfected with the mBD-1 cDNA showed antibacterial activity against gram-positive and gram-negative bacteria . mBD-1 transcripts were found in kidney, liver, and female reproductive organ tissues . In the airways, mBD-1 is expressed diffusely throughout the epithelial cells of the large proximal airways with less expression in the small distal airways and no expression in alveolar cells . The present study demonstrates that a beta-defensin potentially homologous to human beta-defensin 1 is present in the respiratory system and other mucosal surfaces in mice.

Trends Biotechnol, 1998 Feb, 16(2), 82 - 8
Cationic peptides: a new source of antibiotics; Hancock RE et al.; Antimicrobial cationic peptides are an important component of the innate defenses of all species of life . Different peptides may have antibacterial, antiendotoxic, antibiotic-potentiating or antifungal properties, and so they are being developed for use as a novel class of antimicrobial agents and as the basis for making transgenic disease-resistant plants and animals.

Plant Mol Biol, 1998 Feb, 36(3), 473 - 8
Isolation and analysis of a gene bbe1 encoding the berberine bridge enzyme from the California poppy Eschscholzia californica; Hauschild K et al.; A genomic clone, bbe1 was isolated that encodes the methyl jasmonate-inducible berberine bridge enzyme of antimicrobial benzophenanthridine alkaloid biosynthesis in the California poppy Eschscholzia californica . Genomic DNA gel blot analysis indicates that two genes are present in the E . californica genome that code for the berberine bridge enzyme reading frame . Each coding region is apparently preceeded by a unique promoter sequence . The bbe1 gene contains no introns and one transcriptional start site . A 41 nucleotide region between -496 and -455 of the 5'-flanking region appears to be essential for promoter activity in E . californica . The promoter displayed an unexpectedly high species specificity, being active in only E . californica and Thalictrum bulgaricum, out of 28 cell suspension cultures tested.

Handchir Mikrochir Plast Chir, 1997 Nov, 29(6), 307 - 13
{Outcome of treatment of ingrown toe nails in the child}; Heymanns M et al.; Difficulties encountered and long-term results of surgical treatment of ingrown toenails are well documented in the adult patient . In infants and children, however, little is known about this problematic entity . We therefore performed a follow-up study in 91 out of 99 ingrowing toenails in children up to 14 years . The patients were treated in our department from 1990 to 1994 mainly by wedge resection . 64 nail folds remained free of symptoms after single surgical treatment . Recurrence of infection or nail spikes was found in 21 out of 85 nail folds . In children, conservative treatments with antimicrobial ointments, gutter treatment, and in selected cases systemic antibiotics, are more promising than in adults . If these efforts remain unsuccessful, the only reliable surgical approach is a radical wedge resection.

J Formos Med Assoc, 1998 Jan, 97(1), 44 - 8
Capnocytophaga bacteremia: clinical features of patients and antimicrobial susceptibility of isolates; Lin RD et al.; Capnocytophaga has been recognized as an opportunistic pathogen causing systemic infections in immunocompromised individuals with granulocytopenia and oral ulceration . Treatment of Capnocytophaga infection is often empiric . We retrospectively analyzed the clinical features of all patients with Capnocytophaga bacteremia seen at the National Taiwan University Hospital between January 1981 and December 1996 and the antimicrobial susceptibility of the isolates recovered from these patients . All the patients had underlying diseases, namely neoplastic disease (9 patients), hyperthyroidism (1), and bronchiectasis and tetralogy of Fallot (1) . The clinical features of these patients were primary bacteremia (10) and pneumonia (1) . Nine patients had nosocomial bacteremia and 10 patients had monomicrobial bacteremia . None had septic shock . All the patients responded well to appropriate antimicrobial therapy and survived . All isolates were susceptible to amoxicillin-clavulanate, imipenem, ciprofloxacin, erythromycin, clindamycin, tetracycline, and chloramphenicol but resistant to aminoglycosides and sulfamethoxazole-trimethoprim . The susceptibilities to penicillin, ampicillin, piperacillin, cephalosporins, and aztreonam were variable . Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients, especially in the presence of oral mucositis and ulceration.

Antibiot Khimioter, 1997, 42(12), 25 - 8
{Efficacy of pefloxacin in the treatment of complicated relapsing erysipelas}; Kurmanova KB et al.; The effect of antimicrobial agents on the clinical and immunological indices was comparatively studied in 30 patients with relapsing erysipelas complicated by pyoderma . The patients were treated with pefloxacin in a daily dose of 800 mg for 7-10 days (15 patients) and with the routine antibiotics such as benzylpenicillin, ampicillin and erythromycin (15 patients) . The efficacy of the treatment was defined by disappearance of the clinical signs and normalization of the functional immunity status . The pefloxacin effect was evident at early stages of the treatment and observed at least for 3 months after the patient discharge from the hospital . Gradual elimination of the secondary immune deficiency in the convalescents due to sanitation of the infection chronic foci was recorded.

Antibiot Khimioter, 1997, 42(12), 10 - 5
{Antimicrobial properties of pectins and their effects on antibiotics}; Men'shikov DD et al.; The influence of food fibres and plant proteins on microorganisms, bacteriophages, antibiotics and penicillinase was studied in vitro . It was shown that pectin was the only agent that had a bactericidal effect on the most widely distributed pathogenic and opportunistic microorganisms and did not influence indigenic microflora . High concentrations of pectin (> 2 per cent) had an inactivating effect on therapeutic bacteriophages . There was also a decrease in the antimicrobial activity of penicillins . The other agents tested i.e . wheat bran, soya isolate and soybean flour had no influence on microorganisms, bacteriophages and antibiotics . No sorption activity of the food fibres and plant proteins with respect to microorganisms and antibiotics or their effect on penicillinase was observed.

Mikrobiol Z, 1997 Sep-Oct, 59(5), 67 - 82
{The theory and practice of the creation of antisignature oligodeoxyribonucleotides as universal antimicrobial agents (the principles of a drug technology of the 21st century)}; Skrypal' IH; Gene-directed and anti-sense (mRNA-directed) synthetic oligonucleotides (SO) have a common main shortcoming . That is the necessity to introduce intercalators to their composition for the stronger interaction with targets to prevent their separation from the latter by DNA-polymerase and RNA-polymerase complexes which work on genome or with mRNA by ribosomes moving along them . Intercalation leads to considerable loss of SO selectivity in respect to the target . The author substantiates advantages of another type of SO which action is directed to blocking of the function of signature sequences of ribosomal RNA (rRNA) that completely ceases the self-assembly of ribosomal subunits and totally excludes the process of translation and synthesis of proteins . Such type SO advantages are as follows: a) a short chain which includes 8-13 nucleotides altogether; b) absence of the necessity of intercalation; c) high specificity in respect to targets; d) high stability in respect to nucleases action under modification by one of the methods of internucleotide bonds and, e) a possibility to deliver any microorganism to the cells when allowing for auxotrophy of the latter in respect to one or another substance . It is foreseen that antisignature SO can become most promising among the drugs called to block the functions of nucleic acids of the agents of the disease.

Postgrad Med, 1998 Feb, 103(2), 179 - 80, 185-7
Enterohemorrhagic Escherichia coli . A dangerous food-borne pathogen; Qadri SM et al.; Since 1982, several outbreaks of hemorrhagic colitis due to EHEC, or E coli O157:H7, have occurred in the United States and other parts of the world . Contaminated, undercooked ground beef has been most frequently implicated in the outbreaks, although unpasteurized dairy products and other foods have also been the source of infection in sporadic cases . The most common clinical manifestation of EHEC infection is abdominal cramps and watery, bloody diarrhea . HUS secondary to the initial colitis develops in about 10% of patients under 10 years of age . Definitive diagnosis is made by isolation and identification of EHEC in stool samples . Treatment focuses on rehydration and supportive therapy . The use of antimicrobial agents, narcotics, or antimotility agents is not recommended, because they neither shorten the course of illness nor prevent the development of sequelae.

J Clin Periodontol, 1998 Jan, 25(1), 67 - 73
Effects of the anti-androgen finasteride on 5alpha-reductase activity in human gingival fibroblasts in response to minocycline; Soory M et al.; In addition to their antimicrobial properties, tetracyclines have antiinflammatory and pro-anabolic effects on the reparatory potential of connective tissue and bone . The physiologically active androgen 5alpha-dihydrotestosterone (DHT) implicated in matrix synthesis is formed in gingivae from androgen substrates . The aim of this investigation is to study the androgen metabolic response of gingivae to minocycline, in the presence or absence of the anti-androgen finasteride . Chronically inflamed gingival tissue derived from 12 subjects aged 30-50 years and passaged fibroblasts derived from this source, were used for the experiments . Duplicate incubations were performed in Eagle's MEM with 14C-testosterone/14C-4-androstenedione in the presence or absence of minocycline (5-60 microg/ml) or finasteride for 24 h . The androgen substrate 14C-testosterone was metabolised mainly to DHT and 4-androstenedione, while 14C-4-androstenedione was converted mainly to DHT and testosterone . Minocycline at 20-30 microg/ml stimulated the formation of these metabolites from both substrates by 13-25% . In the tissue incubations there were 3- and 2-fold increases in DHT and 4-androstenedione formation (n=12; p<0.01) . The anti-androgen finasteride caused significant inhibition of 5alpha-reductase activity on both substrates at 0.1 & 1.0 microg/ml with total inhibition at 10 & 50 microg/ml (n=3; p<0.01) . Minocycline-induced stimulation of 5alpha-reductase activity was also inhibited by finasteride (n=4; p<0.02) . Since finasteride inhibition of 5alpha-reductase activity is specific for the type 2 isoenzyme associated with anabolic functions of target tissue, this enzyme activity may contribute to some of the cited anabolic tissue responses to minocycline.

J Clin Periodontol, 1998 Jan, 25(1), 1 - 10
Differential effects of systemic metronidazole and amoxicillin on Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in intraoral habitats; Flemmig TF et al.; 48 adult patients with untreated periodontitis harboring subgingival Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis were randomly assigned to receive full mouth scaling alone (control) or scaling with systemic metronidazole plus amoxicillin and supragingivai irrigation with chlorhexidine digluconate (test) . Subgingival plaque and swab samples from tongue, tonsils, and buccal mucosa were taken at baseline, 10 days and 3, 6, 9, and 12 months . A . actinomycetemcomitans was detected in the oral cavity, i.e., subgingival plaque and/or mucous membranes, less frequently in test patients compared to controls at 9 and 12 months (p<0.01), whereas, the intraoral detection frequency of P . gingivalis was significantly reduced only 10 days following therapy (p<0.001) . At any time after therapy, A . actinomycetemcomitans was not detected intraorally in 5 of 10 (50%) test and 1 of 13 (8%) control patients harboring this pathogen at baseline; P . gingivalis was not detected in only 1 of 18 (6%) test and none of the 17 control patients harboring this pathogen at baseline . Although the data indicated that the assessed antimicrobial therapy may suppress A . actinomycetemcomitans from the entire oral cavity below detectable levels over a minimum of 12 months, P . gingivalis persisted or reoccurred.

Mycoses, 1997, 40 Suppl 2, 33 - 6
Mycoses of the urogenital tract; Schiefer HG; Mycotic infections of the urogenital tract are rarely caused by primary fungal pathogens, often however, by opportunistic fungi such as Candida species . Opportunistic fungi infect the urogenital tract either by haematogenous spread from a distant site, or a break of tissue integrity, or by retrograde ascension from the perianal region, or by wound contamination . After an initial polymorphonuclear reaction macrophages may invade giving rise to a granulomatous response . Risk factors for mycotic urogenital infections are extremes of age, long lasting and broad spectrum antimicrobial therapy, diabetes mellitus, immunosuppression, malignancy, x-ray therapy, contaminated i.-v . catheters, oral contraceptives, pregnancy, surgery, obstructive uropathy and indwelling urethral catheters.

Ann Pharmacother, 1998 Jan, 32(1), S22 - 6
Switch therapy with beta-lactam/beta-lactamase inhibitors in patients with community-acquired pneumonia; Ramirez JA; BACKGROUND: Antimicrobial drugs are prescribed inappropriately nearly 50% of the time . To address this problem, a hospital antimicrobial team was formed integrating the talents of infectious disease physicians, pharmacists, microbiologists, infectious control practitioners, and nurses . The primary goal of the team is to provide optimal, cost-effective antimicrobial therapy . OBJECTIVE: To review the principles of streamlining antimicrobial therapy, with an emphasis on antibiotic switch therapy . DISCUSSION: With appropriate guidelines, switch therapy appears to be an important means to provide optimal antimicrobial therapy complementing the many social pressures placed on patients, while positively impacting on the overall cost of treatment . The use of beta-lactam/beta-lactamase inhibitor combinations as the antibiotics for initial intravenous medication to oral combination switch therapy is a viable approach to the treatment of hospitalized patients with community-acquired pneumonia . Preliminary data from our institution were obtained with such a therapeutic approach to assess the clinical efficacy, patient satisfaction with their care, and calculated dollar savings in the overall cost of care . The results of this evaluation strongly support the validity and desirability of such an approach . CONCLUSIONS: The prospective use of a program that incorporates the use of beta-lactam/beta-lactamase inhibitor combinations for intravenous and switch-to-oral drug administration is a cost-effective means of providing optimal antimicrobial therapy for patients with community-acquired pneumonia.

Ann Pharmacother, 1998 Jan, 32(1), S17 - 21
Rational prescribing of extended-spectrum penicillin beta-lactamase inhibitor combinations: focus on ticarcillin/clavulanic acid; Reed MD; OBJECTIVE: To provide an overview of the clinical pharmacokinetics and pharmacodynamics of ticarcillin/clavulanic acid and to reassess traditional dosage recommendations based on contemporary pharmacokinetic and pharmacodynamic principles . DATA SOURCES: Published ticarcillin and clavulanic acid pharmacokinetic data derived from infants and children combined with data obtained from a rigorous, dose-escalation study performed in 12 healthy adults . Pharmacodynamic correlates were derived from published in vitro susceptibility data for the combination drug ticarcillin/clavulanic acid . DATA SYNTHESIS: Limited differences were observed in the pharmacokinetic disposition profiles between ticarcillin and clavulanic acid and relative to subject age . Integration of these data with defined pathogen minimum inhibitory concentrations underscores the appropriateness of an extended dosing interval (e.g., q8h to q12h) for many infections and demonstrates the probable therapeutic interchangeability of the following three intravenous dosing regimens: 3.1 g every 6 hours, 75 mg/kg every 8 hours, and 100 mg/kg every 12 hours of a 30:1 ticarcillin/clavulanic acid combination . CONCLUSIONS: Integration of pharmacokinetic and pharmacodynamic data is an appropriate means to assess/reassess dosing recommendations for antimicrobial agents . Initial ticarcillin/clavulanic acid dose recommendations did not account for known dynamic interactions for this combination antibiotic . Pharmacokinetic data in infants, children, and adults support a less frequent dosing interval (q8h to q12h) for the treatment of infections arising outside the central nervous system.

Ann Allergy Asthma Immunol, 1998 Jan, 80(1), 45 - 9
Evidence for Chlamydia pneumoniae infection in steroid-dependent asthma; Hahn DL et al.; BACKGROUND: Chlamydia pneumoniae is an obligate intracellular respiratory pathogen capable of persistent infection . Seroepidemiologic studies and the results of open-label antimicrobial treatment of patients with non-steroid-dependent asthma have suggested a potential role for C . pneumoniae in asthma . OBJECTIVE: To evaluate the results of antimicrobial treatment in patients with uncontrolled steroid-dependent asthma and serologic evidence suggesting C . pneumoniae infection . METHODS: Three nonsmoking asthmatic patients (aged 13 to 65 years) whose symptoms remained poorly controlled despite daily administration of inhaled and oral steroid (10 to 40 mg/d) . All met serologic criteria for current or recent C . pneumoniae infection . RESULTS: After prolonged treatment (6 to 16 weeks) with clarithromycin or azithromycin all three patients were able to discontinue oral steroids . All three patients have remained well controlled with inhaled antiasthma therapy only during 3 to 24 months of postantibiotic therapy observation . CONCLUSIONS: In adolescent and adult asthmatic patients, Chlamydia pneumoniae infection may contribute to symptoms of asthma that are poorly controlled by steroids . Serologic evidence for C . pneumoniae infection should be sought in such patients . A trial of appropriate antibiotic therapy may be helpful in those patients with high titers of anti-C . pneumoniae IgG antibodies.

Pediatr Res, 1998 Feb, 43(2), 155 - 62
Evolution of immunologic functions of the mammary gland and the postnatal development of immunity; Goldman AS et al.; Physiologic delays in production of immune factors occur in mammals including Homo sapiens . This finding is counter to a basic tenet of biologic evolution, because such delays increase the risk of infections . The disadvantage is, however, offset by defense factors in milk of the species in whom the developmental delay occurs . Reciprocal relationships between the production of immune factors by the lactating mammary gland and the production of those defense agents during early infancy are found in all investigated mammalian species . Thus, the evolution of these processes is closely related . Certain immunologic components of milk are highly conserved, whereas others vary according to the species . The variations most likely evolved by genetic mutations and natural selection . In addition, the immune composition of mammalian milks is associated with developmental delays in the same immunologic agents . Furthermore, most closely related mammals, such as humans and chimpanzees, are most similar in the defense agents in their milks and the corresponding developmental delays in their immune systems . Defense factors in human milk include antimicrobial agents (secretory IgA, lactoferrin, lysozyme, glycoconjugates, oligosaccharides, and digestive products of milk lipids), antiinflammatory factors (antioxidants, epithelial growth factors, cellular protective agents, and enzymes that degrade mediators of inflammation), immunomodulators (nucleotides, cytokines, and antiidiotypic antibodies), and leukocytes (neutrophils, macrophages, and lymphocytes) . Because of a lack of geographic/ethnic variation in the immunologic composition of human milk and corresponding immunologic delays in infants, these evolutionary processes seem stable . This is supported by investigations of diverse populations that indicate that this evolutionary outcome is highly beneficial to human infants.

Arch Pharm (Weinheim), 1997 Dec, 330(12), 372 - 6
Synthesis and antimicrobial activity of some new anilino benzimidazoles; Tuncbilek M et al.; A series of 2-(anilino or 2,6-dichloroanilino)-1,5(6)-disubstituted-1H-benzimidazoles (1-13) were prepared by reaction of several 2-chloro- or 2-chloromethyl-1H-benzimidazoles with aniline derivatives . The prepared compounds were screened for their in vitro antibacterial and antifungal activities . Compounds 2, 8, and 9 exhibited the best activity.

Insect Biochem Mol Biol, 1997 Oct, 27(10), 877 - 86
Treatment of l(2)mbn Drosophila tumorous blood cells with the steroid hormone ecdysone amplifies the inducibility of antimicrobial peptide gene expression; Dimarcq JL et al.; Insects rely on both humoral and cellular mechanisms to defend themselves against microbial infections . The humoral response involves synthesis of a battery of potent antimicrobial peptides by the fat body and, to a lesser extent, by blood cells . The cellular response on the other hand consists of phagocytosis of small microorganisms and melanization and encapsulation of larger parasites . The l(2)mbn cell line, established from tumorous larval hemocytes, represents a system of choice to dissect the molecular events controlling cellular immunity . We report here that l(2)mbn cells can be efficiently induced to differentiate in adherent, macrophage-like cells by treatment with 20-hydroxyecdysone . Ecdysone treatment increases both the phagocytic capacity of l(2)mbn cells and their competence to express antimicrobial genes in response to immune challenge . We also report that expression of several regulatory molecules thought to be involved in the immune response is up-regulated by ecdysone in l(2)mbn cells.

Clin Pharmacokinet, 1998 Jan, 34(1), 25 - 56
Pharmacokinetics of drugs used in critically ill adults; Power BM et al.; Critically ill patients exhibit a range of organ dysfunctions and often require treatment with a variety of drugs including sedatives, analgesics, neuromuscular blockers, antimicrobials, inotropes and gastric acid suppressants . Understanding how organ dysfunction can alter the pharmacokinetics of drugs is a vital aspect of therapy in this patient group . Many drugs will need to be given intravenously because of gastrointestinal failure . For those occasions on which the oral route is possible, bioavailability may be altered by hypomotility, changes in gastrointestinal pH and enteral feeding . Hepatic and renal dysfunction are the primary determinants of drug clearance, and hence of steady-state drug concentrations, and of efficacy and toxicity in the individual patient . Oxidative metabolism is the main clearance mechanism for many drugs and there is increasing recognition of the importance of decreased activity of the hepatic cytochrome P450 system in critically ill patients . Renal failure is equally important with both filtration and secretion clearance mechanisms being required for the removal of parent drugs and their active metabolites . Changes in the steady-state volume of distribution are often secondary to renal failure and may lower the effective drug concentrations in the body . Failure of the central nervous system, muscle, the endothelial system and endocrine system may also affect the pharmacokinetics of specific drugs . Time-dependency of alterations in pharmacokinetic parameters is well documented for some drugs . Understanding the underlying pathophysiology in the critically ill and applying pharmacokinetic principles in selection of drug and dose regimen is, therefore, crucial to optimising the pharmacodynamic response and outcome.

Phys Ther, 1998 Feb, 78(2), 212 - 8
Povidone-iodine solution in wound treatment; Burks RI; Clinicians have used numerous strategies to combat wound infections, including topical and systemic administration of antibiotics, and various antiseptic agents such as hypochlorite (bleach) and hydrogen peroxide have been placed on wounds to kill bacteria or inhibit their growth . A commonly used antimicrobial agent is povidone-iodine (Betadine), a complex of iodine, the bactericidal component, with polyvinylpyrrolidone (povidone), a synthetic polymer . The most common commercial form is a 10% solution in water yielding 1% available iodine . Povidone-iodine is available as a surgical scrub or skin cleanser with a detergent base (0.75% available iodine) or in other forms . Decisions regarding choice of wound treatment involve two basic considerations: (1) how safe is the treatment, and (2) how effective is the treatment . The safety of a wound care treatment may be determined by whether the treatment retards the progress of the wound through the stages of healing (inflammatory, proliferative/reepithelializing, and remodeling) . The efficacy of a wound care treatment (e.g., povidone-iodine) can be judged in vitro by its ability to kill microorganisms and in vivo by whether it decreases the rate or severity of wound infection . The task of evaluating the choice of povidone-iodine solution for treatment of wounds, especially the chronic wounds most often seen in physical therapy practice, is made complex by two factors . First, although there is a large body of research into various aspects of povidone-iodine use in wound care, the results are not always germane to the types of wound treatment most often provided by physical therapists . The relevance of in vitro studies regarding safety and effectiveness to in vivo use with patients may be limited . Much of the published research on wound healing uses animal wound models; however, the applicability of findings in animal studies to human wounds has been questioned.

Am J Med Sci, 1998 Feb, 315(2), 87 - 94
Resistance to antimicrobial chemotherapy: a prescription for research and action; Levin BR et al.; The growing problem of resistance to antimicrobial chemotherapy was discussed by participants at the February 1995 workshop at Emory University on population biology, evolution, and control of infectious diseases . They discussed the nature and source of this problem and identified areas of research in which information is lacking for the development of programs to control of the emergence and spread of resistant bacteria . Particular attention was given to theoretical (mathematical modeling) and empirical studies of the within and between-host population biology (epidemiology) and the evolution of microbial resistance to chemotherapeutic agents . Suggestions were made about the kinds of models and data needed, and the procedures that could be employed to stem the ascent and dissemination of resistant bacteria . This article summarizes the observations and recommendations made at the 1995 meeting and in the correspondence between participants that followed . It concludes with an update on the theoretical and empirical research on the between- and within-host population biology and evolution of resistance to antimicrobial chemotherapy most of which has been done since that meeting.

Am J Med Sci, 1998 Feb, 315(2), 64 - 75
Emerging and reemerging infectious diseases: a multidisciplinary perspective; Stephens DS et al.; Predictions that infectious diseases would be eliminated as a major threat to human health have been shattered by emerging and reemerging infections, among them acquired immunodeficiency syndrome (AIDS), hemorrhagic fevers, marked increases in infections caused by antimicrobial-resistant bacteria, and the resurgence of tuberculosis and malaria . Understanding the dynamics of emerging and reemerging infections is critical to efforts to reduce the morbidity and mortality of such infections, to establish policy related to preparedness for infectious threats, and for decisions on where to use limited resources in the fight against infections . In order to offer a multidisciplinary perspective, 23 infectious disease specialists, epidemiologists, geneticists, microbiologists, and population biologists participated in an open forum at Emory University on emerging and reemerging infectious diseases . As summarized below, the group addressed questions about the definition, the identification, the factors responsible for, and multidisciplinary approaches to emerging and reemerging infections.

Swed Dent J, 1997, 21(5), 185 - 91
Identification of caries risk children and prevention of caries in pre-school children; Holst A et al.; A special model for dental care in pre-school children was used in a small clinic in the county of Blekinge in southern Sweden . The model is based on screening of caries risk performed by a dental assistant before the caries attack . Any single risk factor or risk behavior in pre-school children was considered . The aim was to 1) evaluate the dental assistant's selection of caries risk children up to the age of three years, 2) compare dental health variables in 4 yr olds in the test clinic with those for the whole county in 1994 and 3) compare time spent by the dentist and the dental assistant in the test clinic and in the whole county per child up to the age of four . 102 children participated . One specially trained dental assistant screened all children using background factors combined with clinical examinations at ages 1, 2 and 3 . Eighty-two children participated each year from one year . A systematized form for questioning the parents was used . Individual caries prevention was given including fluoride and antimicrobial treatments as well as fissure sealants in primary molars at caries risk . The proportion of children with caries lesions at four years and a caries risk assessment up to the age of two was 1.0 (sensitivity) . The proportion of children with no caries lesions at four years and no caries risk assessment at year two was 0.7 (specificity) . The most frequent risk factors found at 2 yrs were frequency order: lack of oral hygiene (visible plaque), deep fissures in molars and frequent intakes of sweet drinks . The proportion of children with no caries lesions at 4 yrs of age in the test clinic was 92.9% compared to a county mean of 76.4% . In the group of children where a risk assessment was made each year from one year the proportion of caries free children was 96.3% . The total time spent per child in the test clinic was 22 minutes more than the county mean . However, dentist's time, excluding assistance, was 28 minutes less in the test clinic . The results suggest that the model used for caries prevention in pre-school children is cost-effective, and that dental health can be remarkably improved.

J Dent Hyg, 1997 Summer, 71(4), 159 - 61
Erythromycin: drug interactions; Gurevitz SL; The purpose of this article is to provide the dental hygienist with an understanding of potential drug interactions that can occur between the antimicrobial agent, erythromycin, and other medications . Erythromycin is the drug-of-choice against oral infections and to prevent infective endocarditis in patients who are allergic to penicillin . Erythromycin has the potential to interact with many medications by inhibiting drug metabolism in the liver . Several reports and controlled studies have shown that erythromycin may interact with theophylline, carbamazepine, cyclosporin, tacrolimus, warfarin, digoxin, terfenadine, astemazole, cisapride, lovastatin, triazolam, and disopyramide . During data collection, the hygienist can identify potential drug interactions with erythromycin . The majority of these interactions can be safely managed by using another antimicrobial with a similar spectrum of activity . If this cannot be done, the patient's physician should be consulted.

Rapid Commun Mass Spectrom, 1998, 12(2), 53 - 6
New caerin 1 antibiotic peptides from the skin secretion of the Australian tree frog Litoria chloris . Part 2 . Sequence determination using electrospray mass spectrometry; Wabnitz PA et al.; Electrospray mass spectrometry and automated Edman sequencing provides the structures of two new caerin 1 antimicrobial peptides from the skin glands of the Australian tree frog Litoria chloris . These are: caerin 1.8 Gly Leu Phe Lys Val Leu Gly Ser Val Ala Lys His Leu Leu Pro His Val Val Pro Val Ile Ala Glu Lys Leu (NH2), and caerin 1.9, Gly Leu Phe Gly Val Leu Gly Ser Ile Ala Lys His Val Leu Pro His Val Val Pro Val Ile Ala Glu Lys Leu (NH2).

Lakartidningen, 1998 Jan 21, 95(4), 279 - 81
{Antibiotic resistance among strains of Helicobacter pylori in Gothenburg . Bacteria resistant to metronidazole}; Jaup BH et al.; AIM: Primary resistance of H pylori strains to antimicrobials has direct therapeutical implications . For this reason we studied the prevalence of primary resistance of H pylori of Sweden, in a regional setting . MATERIAL AND METHODS: A total of 244 patients referred to our endoscopy unit have been evaluated prospectively for the occurrence of H pylori . Helicobacter pylori infection was established by a positive rapid urease test on an antral biopsy . If positive the biopsy specimen was transferred to a transportmedium for culture on a Skirrow medium . Antimicrobial resistance was evaluated by the E-test . RESULTS: In 109 patients H pylori infection was seen and in all of them the culture was positive . No resistance was seen for amoxycillin and tetracycline . The resistance against metronidazole was 40.3% and and against clarithromycin it was 2.8% . For metronidazole there was a significantly higher resistance seen in women compared to men (53.3% vs 31.2%; p < 0.001) . CONCLUSIONS: Primary resistance to metronidazole was higher than expected and over average in Europe . The resistance for clarithromycin is still rare . Further monitoring is mandatory to detect changes in the community.

J Pharm Belg, 1997 Nov-Dec, 52(6), 213 - 6
{Synthesis and antimicrobial activity of some substituted 3-arylidenaminothienopyrimididones}; De Oliveira RC et al.; The synthesis of six 2-methyl-3-arylidenoaminocyclohexeno {b} thieno {2,3-d}-3,4-dihydropyrimidin-4-ones is described . The biological activity of these new compounds was screened against several Gram-positive and Gram-negative bacteria . The activity of our compounds is 5 to 320 fold less active than ciprofloxacin.

Eur J Med Res, 1996 Mar 19, 1(6), 312 - 4
The impact of microbiological diagnostics on the antimicrobial treatment of hospitalised patients with infectious disease; Vogel F et al.; We evaluated a total of 160 treatment protocols from the unit of internal medicine (n = 100) and the intensive care unit (n = 60) of the Bonn University Hospital to detect the influence of microbiological diagnostics on the individual antimicrobial treatment . Ninety-six of hundred patients in regular care were set on empirical antibiotic treatment within 24 to 48 hours after onset of symptoms . In 91% of the cases cure or substantial improvement was achieved via the initial therapy . Microbiological survey revealed multi-resistant pathogens which could be handled using a specific treatment in six of the remaining patients . In contrast, sixty patients in intensive care proved to benefit significantly from microbiological diagnostics . In one quarter of the cases microbiological findings supported the decision on a reasonable escalated therapy, and in another quarter the initial therapeutic schedule could be confirmed . At any rate, about one third of the infections remained bacteriologically inexplicable in spite of excessive microbiological research . Thus, the results of this retrospective evaluation confirm the common practice of an initial antibiotic treatment without bacteriological investigation in less severe and in severe infections . Microbiological screening may help to decide on effective routine antibiosis in patients with less severe infections . We recommend comprehensive individual microbiological diagnostics in patients with severe nosocomial pneumonia or sepsis and in patients at high risk for Candida superinfections . Due to steadily increasing economic pressure, it is necessary to reflect on the expenditure for microbiological diagnostics . The cost-effectiveness-ratio may be optimised mainly in patients with less severe infections and in regular care . The number of microbiological surveys and expenditures in ICU patients appeared adequate as compared to the individual benefit.

J Leukoc Biol, 1998 Jan, 63(1), 94 - 100
Anti-HIV-1 activity of indolicidin, an antimicrobial peptide from neutrophils; Robinson WE Jr et al.; Indolicidin is a tridecapeptide amide isolated from the cytoplasmic granules of bovine neutrophils . It has potent, broad spectrum microbicidal activities in vitro that are thought to be related to the membrane-disruptive properties of the peptide . Based on the putative membrane-targeted mode of action, we postulated that indolicidin would be active against HIV-1, an enveloped virus . Indolicidin was reproducibly virucidal against HIV-1 at a concentration of 333 microg/mL (174 microM) with a 50% inhibitory dose between 67 and 100 microg/mL . At 37 degrees C, killing was rapid with >50% killing of HIV occurring within 5 min, and nearly 100% viral inactivation achieved by 60 min . The anti-HIV activity of indolicidin was temperature-sensitive, a finding consistent with a membrane-mediated antiviral mechanism . Parallel experiments revealed that indolicidin lysed cultured lymphoblastoid cells at concentrations similar to those required for antiviral activity . However, a des-R13-amide indolicidin analog (R12-OH), previously shown to have less antibacterial activity than indolicidin, was significantly less active against HIV and was non-toxic to lymphoid target cells at concentrations up to 333 microg/mL, the highest level tested.

FEBS Lett, 1998 Jan 16, 421(3), 263 - 7
Oligomerization of protegrin-1 in the presence of DPC micelles . A proton high-resolution NMR study; Roumestand C et al.; Protegrins are members of a family of five Cys-rich naturally occurring cationic antimicrobial peptides . The NMR solution structure of protegrin-1 (PG-1) has been previously determined as a monomeric beta-hairpin both in water and in dimethylsulfoxide solution . Protegrins are bactericidal peptides but their mechanism of action is still unknown . In order to investigate the structural basis of their cytotoxicity, we studied the effect of lipid micelles on the structure of PG-1 . The NMR study reported in the present work indicates that PG-1 adopts a dimeric structure when it binds to dodecylphosphocholine micelles . Moreover, the amide proton exchange study suggests the possibility of an association between several dimers.

Crit Care Med, 1998 Feb, 26(2), 236 - 44
Diagnostic accuracy of protected specimen brush and bronchoalveolar lavage in nosocomial pneumonia: impact of previous antimicrobial treatments; Souweine B et al.; OBJECTIVE: To determine whether the diagnostic accuracy of bronchoscopy samples in patients with suspected ventilator-associated pneumonia is affected by prior antibiotic treatment given for a previous infection, and/or by antibiotic treatment recently started to treat suspected ventilator-associated pneumonia . DESIGN: Study of critically ill patients . SETTING: Intensive care unit in a university hospital . PATIENTS: Sixty-three episodes of suspected ventilator-associated pneumonia were prospectively evaluated . Based on prior antibiotic treatment, three groups were defined: no antibiotic group (no previous antibiotic treatments), n = 12; current antibiotic group (antibiotic treatment initiated >72 hrs earlier), n = 31; and recent antibiotic group (new antibiotic treatment class started within the last 24 hrs), n = 20 . INTERVENTIONS: Fiberoptic bronchoscopy with quantitative protected specimen brush cultures, bronchoalveolar lavage cultures, and intracellular organism counts of bronchoalveolar lavage cells . MEASUREMENTS AND MAIN RESULTS: The diagnosis of ventilator-associated pneumonia was made in 35 cases, based on histology (n = 2), cavitation (n = 2), blood cultures (n = 4), or outcome under appropriate antibiotic treatment (n = 27) . The discriminative value of the tests, based on the area under the receiver operating characteristic curve, was high (> or =0.85) in both current antibiotic treatment and recent antibiotic treatment patients . Sensitivities for a 5% intracellular organism count of bronchoalveolar lavage cells, a protected specimen brush culture threshold of 10(3) colony-forming units (cfu)/mL, and a bronchoalveolar lavage culture threshold of 10(5) cfu/mL were as follows, respectively, in the three groups: 0.71, 0.88, and 0.71 (no antibiotic treatment group); 0.5, 0.77, and 0.83 (current antibiotic group); and 0.67, 0.40, and 0.38 (recent antibiotic group) . Specificity was consistently > or =0.9 . In the recent antibiotic group, protected specimen brush and bronchoalveolar lavage cultures had lower sensitivities (p < .05), and the best threshold values for these two tests were 10(2) cfu/mL and 10(3) cfu/mL, respectively . CONCLUSIONS: After recent introduction of an antibiotic treatment for suspected ventilator-associated pneumonia, protected specimen brush and bronchoalveolar lavage culture thresholds must be decreased to maintain good accuracy . In contrast, current antibiotic treatment prescribed for a prior infectious disease does not modify the diagnostic accuracy of protected specimen brush or bronchoalveolar lavage.

Comp Biochem Physiol B Biochem Mol Biol, 1997 Nov, 118(3), 515 - 21
Styelins, broad-spectrum antimicrobial peptides from the solitary tunicate, Styela clava; Lee IH et al.; Two novel phenylalanine-rich antimicrobial peptides, Styelin A and Styelin B, were purified from the hemocytes of Styela clava . The peptides had very similar masses (Styelin A, 3685.8; Styelin B, 3700.6) and amino acid compositions, and at least 17 of their first 20 N-terminal residues were identical . Both Styelins were effective against a panel of gram negative and gram positive bacterial pathogens of humans, usually acting with minimal inhibitory concentrations < 1.5 microgram/ml (< 0.5 microM), even in the presence of 100 mM NaCl . Styelins also killed marine bacteria, Psychrobacter immobilis and Planococcus citreus, in media containing 0.4 M NaCl . The presence of antimicrobial peptides (Styelins) in tunicate hemocytes is evidence that such molecules are ancient mediators of host defense within the vertebrate lineage . Peptide antibiotics from marine organisms could afford design template for the development of topical microbicides that manifest broad-spectrum antibacterial activity in the presence of physiological or elevated NaCl concentrations.

Radiats Biol Radioecol, 1997 Nov-Dec, 37(6), 855 - 9
{Immunological aspects of the effects of low-dose gamma irradiation: nonspecific factors of protection and immunological reactivity of poultry}; Pokrovskii BS; The low doses of gamma-irradiation activate the factors of nonspecific protection of the poultry organisms . There is the rise of antimicrobial characteristics of skin and mucous membrane of oral cavity of bactericide ability of blood serum due to increased content of lysozyme, beta-lysin and number of normal antibodies in it . Gamma-irradiation promotes the formation of a stronger immunity and a favourable outcome of an infectious process.

J Clin Epidemiol, 1998 Jan, 51(1), 61 - 8
Inappropriateness and variability of antibiotic prescription among French office-based physicians; Guillemot D et al.; OBJECTIVE: To describe oral antibiotic prescription in the community . DESIGN: Audit of anti-infective prescribing in office-based medical practice . SETTING: Center of France, in the Loiret, a 600,000 inhabitant administrative division . MAIN OUTCOME MEASURES: Clinical hypothesis and antimicrobial drugs used as well as daily doses and durations of treatment . RESULTS: Respiratory tract infections with a presumed viral etiology accounted for 36% of prescriptions . In children, a high percentage of antibiotic prescriptions were underdosed as compared to clinical recommendations, particularly in acute otitis media . The variability of the daily dose was high, with coefficients of variation over 40% in acute otitis media or acute tracheobronchitis . Whatever the clinical hypothesis, the duration of treatment was close to 8 days . In acute otitis media, the coefficient of variation was 14%, the lowest for all diagnoses . CONCLUSION: Our investigation identified two main areas for improving antimicrobial drug prescribing: (1) reduction of useless prescriptions in respiratory tract infections with a presumed viral etiology, and (2) increasing the prescribed daily dose of antimicrobials to the recommended levels.

J Clin Microbiol, 1998 Feb, 36(2), 421 - 6
Nosocomial Candida glabrata colonization: an epidemiologic study; Vazquez JA et al.; Candida glabrata has emerged as an important nosocomial pathogen, yet little is known about its epidemiology . We prospectively followed 98 patients admitted to a medical intensive care unit and the bone marrow transplant unit of a university hospital . Samples from environmental surfaces and the hands of hospital personnel were also cultured . Patients with newly acquired C . glabrata strains were compared to controls who were culture negative for C . glabrata . C . glabrata was recovered from multiple sites from 24 patients and three environmental surfaces . Sixteen patients (17%) acquired C . glabrata after admission to the study units . Significant risk factors for the nosocomial acquisition of C . glabrata were prolonged duration of hospitalization in the unit and prior antimicrobial use . Strain delineation by restriction enzyme analysis revealed 28 different strains of C . glabrata; three strain types were common to nine patients . The environmental isolates were of the same strain type and common to five patients (four patients with newly acquired strains) . These results suggest the possibility of exogenous nosocomial acquisition of C . glabrata, including the possible acquisition from the hospital environment . Transmission may be by indirect contact since identical strains of C . glabrata were recovered from patients who were geographically and temporally associated.

J Infect Dis, 1998 Feb, 177(2), 492 - 7
Trends in antimicrobial drug use in the community--France, 1981-1992; Guillemot D et al.; Trends in the use of antimicrobials in France between 1980-1981 and 1991-1992 were analyzed . Data were obtained from surveys of health and ambulatory care, which were based on national probability samples . In a 3-month period in 1980, 17% of the population of France was treated with an antibiotic, compared with 25% in 1991 (P < .001) . The frequency of respiratory tract infections with a presumed viral etiology that were diagnosed and treated with antibiotics increased by 86% for adults and 115% for children in the 11-year period . The proper use of cephalosporins must be encouraged, and vigilance is required in view of the increased improper use of fluoroquinolones, mainly for respiratory tract infections with a presumed viral etiology.

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