Pediatr Infect Dis J, 1994 Oct, 13(10), 878 - 82 Antimicrobial therapy for children with chronic suppurative otitis media without cholesteatoma; Arguedas A et al.; This study was designed to determine the middle ear bacterial pathogens, the frequency of serum immunoglobulin deficiency and the efficacy of medical management in patients with chronic suppurative otitis media without cholesteatoma . This was an open noncomparative clinical trial performed at the National Children's Hospital, San Jose, Costa Rica, and included 186 patients older than 2 months of age with a confirmed diagnosis of chronic suppurative otitis media without cholesteatoma . Middle ear cultures and serum for immunoglobulin determinations were obtained on admission . The first 40 patients were treated only with ceftazidime and from patient 41 and up, if a Gram-positive organism was cultured, oxacillin was added to (for combined infection) or replaced ceftazidime . Parenteral antibiotics and suction twice daily were continued until three days after the middle ear became dry . Trimethropimsulfamethoxazole prophylaxis was administered during the follow-up period . Middle ear bacterial cultures were positive in 166 patients . Pseudomonas sp . (35.6%), enteric Gram-negative organisms (28.7%) and Gram-positive cocci (26%) were the most common organisms . Immunoglobulin determinations were below normal in 3 of 69 (4.3%) evaluable patients . Dryness of the ear was achieved in 174 patients (93.5%) including 130 of 139 patients treated with ceftazidime, 28 of 28 patients treated with oxacillin and 14 of 14 patients treated with ceftazidime and oxacillin . Recurrent otorrhea developed in 39 (23.4%) patients . Twice-daily canal aspiration and parenteral ceftazidime for Gram-negative organisms and/or oxacillin for Gram-positive bacteria for 3 days after dryness of the middle ear followed by prophylactic oral antimicrobials are effective for treatment of most chronic suppurative otitis media without cholesteatoma patients. Trends Microbiol, 1994 Oct, 2(10), 422 - 5 Antimicrobial resistance: prognosis for public health; Cohen ML; Antimicrobial resistance poses a significant threat to public health worldwide, with certain infections already being untreatable with antibiotics . Increasing resistance is resulting from antimicrobial use coupled with various epidemiological factors that enhance transmission of drug-resistant organisms, and the problem is likely to worsen . Control of antimicrobial resistance is feasible, but will be difficult. Trends Microbiol, 1994 Oct, 2(10), 366 - 71 Detection and surveillance of antimicrobial resistance; Sahm DF et al.; The clinical microbiology laboratory is strategically positioned to recognize changing patterns in bacterial resistance to antimicrobials . This requires the application of accurate testing methods and a methodological survey of drug-resistance patterns among clinically important bacteria . This information can be assembled into comprehensive international databases, using a common format to facilitate monitoring. Am J Hosp Pharm, 1994 Oct 1, 51(19), 2403 - 8 Conformity with guidelines for antimicrobial prophylaxis against bacterial endocarditis; Sagert G et al.; The extent to which prescribed antimicrobial prophylaxis against bacterial endocarditis conformed with American Heart Association (AHA) guidelines was determined and the frequency of nonconformity with specific elements of the guidelines was evaluated . Patients with conditions defined by AHA as placing them at risk for developing endocarditis were identified through medical records for a four-year period at an 850-bed hospital . Data about the procedures they underwent and prophylaxis prescribed were compared with the AHA guidelines . Conformity with the guidelines was evaluated according to whether prophylaxis was recommended, optional, or unnecessary; nonconformity with specific elements of the guidelines (indication, choice of antimicrobial, dose, dosage interval, timing, and duration) was also evaluated . The following variables were evaluated for possible association with nonconformity to the guidelines: patient's age and sex, penicillin allergy, use of a consultant, and whether the procedure was the first performed in the patient after identification of the cardiac condition . Of the 131 cases analyzed, 29 (22%) involved prophylaxis that conformed with the AHA guidelines . Conformity with the guidelines was significantly lower when prophylaxis was recommended or optional than when it was unnecessary . Nonconformity was most common with the following elements: indication, choice of antimicrobial, and dose . Recommended prophylaxis was given more often in children than in adults and more often before first procedures than before subsequent procedures . More of the regimens prescribed for children exceeded the recommended duration than those prescribed for adults . Unnecessary prophylaxis was given more often when a consultant was involved than when no consultant was involved . In hospitalized patients, conformity with AHA guidelines for antimicrobial prophylaxis against endocarditis was low. Antimicrob Agents Chemother, 1994 Oct, 38(10), 2440 - 8 In vitro model to assess effect of antimicrobial agents on Encephalitozoon cuniculi; Beauvais B et al.; We have developed a new micromethod to study the effect of drugs on microsporidia, using MRC5 fibroblasts infected by 10(5) spores of Encephalitozoon cuniculi . After 3 days of incubation with various concentrations of drugs, parasitic foci were counted in stained cultures . The inhibition of microsporidial growth exceeding 90% with albendazole (0.005 microgram/ml), fumagillin (0.001 microgram/ml), 5-fluorouracil (3 micrograms/ml), and sparfloxacin (30 micrograms/ml) was observed . Chloroquine, pefloxacin, azithromycin, and rifabutin were partially effective, at high concentrations . Arprinocid, metronidazole, minocycline, doxycycline, itraconazole, and difluoromethylornithine were not evaluable, since concentrations that inhibited microsporidia were also toxic for fibroblasts . Pyrimethamine, piritrexim, sulfonamides, paromomycin, roxithromycin, atovaquone, and flucytosine were ineffective . Our results confirm that albendazole and fumagillin have marked activity against E . cuniculi and show the antimicrosporidial activity of 5-fluorouracil and sparfloxacin . These data may form the basis for treatment of Encephalitozoon hellem and Septata intestinalis infections and represent an attempt to identify drugs effective against Enterocytozoon bieneusi. Antimicrob Agents Chemother, 1994 Oct, 38(10), 2287 - 95 Potential drug targets for Mycobacterium avium defined by radiometric drug-inhibitor combination techniques; Rastogi N et al.; Previously established radiometric techniques were used to assess the effectiveness of combined antimicrobial drug-inhibitory drug (drug-inhibitor) treatment on two clinical isolates of the Mycobacterium avium complex representing three colony variants: smooth opaque (dome) (SmO), smooth transparent (SmT), and rough (Rg) . All variants were identified as members of the M . avium complex; however, only the SmT colony type of strain 373 possessed characteristic serovar-specific glycopeptidolipid (GPL) antigens . MICs, determined radiometrically, of drugs with the potential to inhibit the biosynthesis of GPL antigens or other cell envelope constituents were similar for all strains . These drugs included cerulenin, N-carbamyl-DL-phenylalanine, N-carbamyl-L-isoleucine, trans-cinnamic acid, ethambutol, 1-fluoro-1-deoxy-beta-D-glucose, 2-deoxy-D-glucose, and m-fluoro-phenylalanine . The MICs of the antimicrobial drugs amikacin, sparfloxacin, and clarithromycin varied, but overall the MICs for the SmO variant were the lowest . Radiometric assessment of drug-inhibitor combinations by using established x/y determinations revealed enhanced activity when either ethambutol or cerulenin were used in combination with all antimicrobial agents for all variants except the Rg variant of strain 424, for which ethambutol was not effective . Enhanced activity with amino acid analogs was observed with the Rg colony variants of strains 373 and 424 . Two potential sites for drug targeting were identified: fatty acid synthesis, for all strains assayed, and peptide biosynthesis, particularly for Rg colony variants that possess previously identified phenylalanine-containing lipopeptides as potential targets for future drug development. Farmaco, 1994 Oct, 49(10), 633 - 9 New 1-{quinolyl(4)}-1,2,3-triazoles: synthesis and evaluation of antiinflammatory and analgesic properties . II; Savini L et al.; Several 1-{quinolyl(4)}-1,2,3-triazoles were synthesized by 1,3-dipolar cycloaddition of 4-azidoquinolines with activated methylene compounds . The synthesized compounds, tested for antiinflammatory and analgesic activities, resulted moderately active as antiinflammatories, but with a very interesting analgesic activity, sometimes higher than that of indomethacin, used as reference drug . Some of the triazole derivatives were evaluated also as antimicrobial, but none of them exhibited activity. Acta Paediatr Jpn, 1994 Oct, 36(5), 585 - 91 A review: the active peptide of lactoferrin; Tomita M et al.; A potent antimicrobial peptide, 'lactoferricin', was found to be generated upon gastric pepsin cleavage of lactoferrin . The active peptide consists mainly of a loop of 18 amino acid residues, derived from the N-terminal region of the lactoferrin molecule . Like various other antimicrobial peptides that display membrane-disruptive properties, it contains a high proportion of basic amino acid residues . A physiologically diverse range of micro-organisms was tested and found to be susceptible to inhibition by this natural peptide including Gram-negative and Gram-positive bacteria, yeasts and filamentous fungi . Its antimicrobial effect against sensitive micro-organisms was lethal . Electron microscopy studies revealed that it induces a profound change in cell ultrastructural features and causes substantial cell damage in bacteria and fungi . These findings suggest the possibility that active peptides of lactoferrin may have a role in the host defense against microbial disease . If produced in substantial quantities in vivo such peptides could have important physiological significance, especially in nursing infants. J Clin Microbiol, 1994 Oct, 32(10), 2564 - 8 Testing antimicrobial susceptibilities of adherent bacteria by a method that incorporates guidelines of the National Committee for Clinical Laboratory Standards; Domingue G et al.; Membrane filters (0.22-microns pore size) were colonized with 10(4) CFU of logarithmic-phase bacteria per filter under laminar flow conditions in a Modified Robbins Device . Colonized filters were then placed upon agar dilution plates for MIC determinations . Subsequently, filters were transferred to control plates and incubated to obtain MBCs. Clin Pediatr (Phila), 1994 Oct, 33(10), 611 - 6 Multifocal M . intracellulare osteomyelitis in an immunocompetent child; Raszka WV Jr et al.; We report the successful treatment of disseminated Mycobacterium intracellulare osteomyelitis, without evidence of other visceral involvement, in a previously healthy, HIV-negative, 2-year-old female using a 23-month regimen of antimicrobial agents that included 18 months of oral therapy with azithromycin, rifabutin, trimethoprim-sulfamethoxazole (TMP/SMX), and ethambutol. Oral Microbiol Immunol, 1994 Oct, 9(5), 315 - 7 Effect of chlorhexidine and toothbrushing on the presence of bacteria on gingival and buccal epithelial cells; Vaahtoniemi LH et al.; Swabs of buccal and gingival epithelial cells from healthy young adult donors were washed in physiological saline solution, smeared on glass slides and stained with acridine orange . The presence of bacteria attached onto epithelial cells was examined under a fluorescence microscope . Four hours after a chlorhexidine rinse, the number of cells with > 50 attached bacteria had almost completely vanished . The degree of bacterial colonization seemed to re-establish at a level exceeding the baseline . One week after chlorhexidine treatment the degree of colonization was still over the control level . Toothbrushing with a conventional toothpaste reduced immediately the number of cells with > 50 bacteria . The colonization had re-established to the pre-washing levels at the buccal sites at 1 h and at the gingival sites at 4 h after toothbrushing . A method for the evaluating of the antimicrobial power of oral hygiene products is presented. Dent Clin North Am, 1994 Oct, 38(4), 719 - 31 Antimicrobials in periodontal practice; Hancock EB et al.; Antimicrobial agents provide an additional means of combating the infective agents encountered in the periodontal diseases . Delivery methods include oral rinses, dentifrices, irrigation, local delivery, and systemic administration . Agents and delivery methods should be selected with the following criteria in mind: 1 . The agent must be effective against the organisms present . 2 . The agent must reach the desired site of action in appropriate concentration . 3 . The agent must remain at the site for a sufficient period of time . When combined with a careful patient assessment and a considered diagnosis, the use of antimicrobial agents may prove to be an important adjunct in total periodontal therapy. Dent Clin North Am, 1994 Oct, 38(4), 689 - 706 The management of odontogenic infections . A rationale for appropriate chemotherapy; Baker KA et al.; Odontogenic infections are one of the most frequently occurring infectious processes known to health practice . Significant changes have occurred in the use of antibiotics and antimicrobials since the use of chemotherapeutic agents became widespread . This article provides some important considerations for selecting appropriate chemotherapeutic agents during the management of odontogenic infections. Khirurgiia (Mosk), 1994 Oct, (10), 29 - 32 {Prevention of incompetence of sigmoid-rectal anastomosis after frontal resection of rectum in the treatment of cancer}; Briusov PG et al.; Planned anterior resection of the rectum for carcinoma was conducted in 111 patients, 38 of them underwent low resection . The formation of relieving transversostomy is suggested as a method for the prevention of early postoperative complications resulting from incompetence of the anastomosis . It was formed in 51.3% of cases . Besides, for preventing incompetence of sigmoidorectal anastomoses, connecting antimicrobial elements with kanmycin, dioxydin, and cephamezin were applied in 27 patients (26.2%) . Incompetence of the anastomosis was not encountered in such cases . Complications occurred in the immediate postoperative period in 45 patients (40.5%), 14 of them (12.6%) had incompetence of the anastomosis suture . There were no fatal outcomes . The authors believe relieving transversostomy to be expedient mainly in low resection of the rectum and in patients with partial obstruction of the large intestine. Indian J Lepr, 1994 Oct-Dec, 66(4), 443 - 8 Pefloxacin in leprosy; Bharti R; Fluoroquinolones, a new class of compounds characterised by broad antimicrobial spectrum including mycobacteria together with limited toxicity, have recently been introduced in the chemotherapy of various human infectious diseases . Pefloxacin, one of the members of this class, was recently demonstrated to be bactericidal against M.leprae in the mouse foot-pad model and clinically beneficial in lepromatous leprosy patients . Clinical response to standard MDT with added pefloxacin in ten previously untreated (both PB and MB) was compared with that in ten similar patients on MDT alone in the present trial . The results of chemotherapy were quantified by a method of clinical scoring . This pilot study showed that addition of pefloxacin led to significant and rapid clinical improvement . There were no side effects attributable to pefloxacin. Immunobiology, 1994 Oct, 191(4-5), 578 - 83 Use of liposome preparation to treat mycobacterial infections; Bermudez LE; Infections caused by organisms of the genus mycobacteria, such as tuberculosis M . avium disseminated infection in AIDS patients and leprosy, are extremely common around the world . Mycobacteria are intracellular organisms that invade and multiply chiefly within phagocytic cells . Antibiotic resistance among mycobacteria is a growing concern . M . tuberculosis resistant to INH and rifampin are increasing in major urban centers of the developed and in the developing world . M . avium is characteristically resistant to most anti-tuberculosis antibiotics . Furthermore, therapy of mycobacterial infections takes a long time and most of the drugs have potential side effects and toxicity . In addition, mycobacteria is found within cells and antimicrobials need to be able to achieve adequate concentration within the compartment where mycobacteria is located . Liposome preparations, containing antibiotics, have a theoretical advantage in being able to deliver high concentrations of antimicrobials into the infected cell . Studies done thus far, in vitro and in vivo, have confirmed this premise, when comparing drug entrapped in liposomes with free drug . This paper summarizes the results obtained using liposome preparations to treat mycobacterial infections. J Toxicol Sci, 1994 Oct, 19 Suppl 2, 281 - 94 {Single-dose toxicity study and twenty-eight-days intravenously repeated dose toxicity study of desethyl-piperacillin in rats}; Nakamura S et al.; Desethyl-piperacillin (desethyl-PIPC) is an active metabolite of PIPC which was newly found in clinical field . We carried out a single intravenous toxicity study at the dosage of 2000 mg/kg, and 28-days intravenous toxi-city study at the daily dosage of 400 mg/kg followed by 28-days recovery study using both sexes of rats . The following results were obtained . In the single dose toxicity study, no deaths occurred in rats injected 2000 mg/kg of desethyl-PIPC, therefore it is presumed that minimal lethal dose of desethyl-PIPC is over 2000 mg/kg in both sexes . As clinical signs, decrease in locomotor activity, deep breath and loose stool were observed . In the patho-logical study, dilatation of cecal lumen was observed macroscopically, but no significant changes were observed histologically . In the repeated dose toxicity study, loose stool, increase in water consumption, dilatation of cecal lumen and increase in its weight were noted . These abnormal findings were considered to be due to antimicrobial activity of desethyl-PIPC . In addition, decrease in the ratio of serum gamma-globulin and increase in the ratio of alpha 1-globulin were observed, but A/G ratio was not affected . After withdrawal of desethyl-PIPC administration, these abnormal findings tended to disappear . As mentioned above, the minimal lethal dose of desethyl-PIPC is over 2000 mg/kg in the single dose toxicity study and abnormal signs were slight in the repeated dose toxicity study at the dosage of 400 mg/kg of desethyl-PIPC for 28 days in rats . It is, therefore, concluded that desethyl-PIPC is a low toxic metabolite of PIPC. Drugs, 1994 Oct, 48(4), 599 - 616 Dirithromycin . A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy; Brogden RN et al.; Dirithromycin is a new macrolide with a spectrum and degree of in vitro antimicrobial activity similar to that of erythromycin . Compared with erythromycin, dirithromycin has a long elimination half-life enabling once-daily administration, and it also achieves a greater cellular:extracellular concentration ratio and higher concentration in some tissues . Multicentre double-blind clinical trials have shown dirithromycin to be similar in efficacy to erythromycin in the treatment of uncomplicated bacterial infections of the respiratory tract and of skin and soft tissues . Since dirithromycin is at least as well tolerated as erythromycin, with its convenient administration schedule and pharmacokinetic profile it is a useful alternative to erythromycin in the treatment of appropriate community-acquired infections . Definition of the place of dirithromycin relative to that of the other newer macrolides awaits the results of further suitably designed therapeutic trials. Drugs, 1994 Oct, 48(4), 528 - 48 Recognition and treatment of shingles; Nikkels AF et al.; Varicella zoster virus (VZV) is responsible for a primary infection (varicella) followed by a latency, eventually resulting in herpes zoster (shingles) . The replication cycle of VZV is normally interrupted after varicella . Consequently, VZV remains dormant in the organism . Reactivation occurs after viraemia, and the development of tissue alterations (skin and viscera) depends on the immunological status of the patient . Diagnosis of herpes zoster relies on clinical recognition and cytological and histological evaluations combined with immunohistochemistry and molecular biology techniques . Treatment of herpes zoster primarily relies upon antiviral drugs and incidentally on immunomodulating agents, specific immunoglobulins, antimicrobial agents, antiviral enzymes and corticosteroids . Drugs with a clinically relevant activity against varicella zoster virus infections include aciclovir, adenosine monophosphate, bromodeoxyuridine, desciclovir, fiacitabine, idoxuridine, interferon-alpha and vidarabine . Among them, aciclovir appears to be a first-line agent . Its efficacy has been well established by many clinical studies . Promising drugs for the future include famciclovir, penciclovir, valaciclovir and other molecules currently under investigation . Recent and promising improvements in antiviral drug development may increase patient compliance, cost-benefit ratios and therapeutic efficacy. N Engl J Med, 1994 Sep 29, 331(13), 854 - 60 Assessment and management of foot disease in patients with diabetes; Caputo GM et al.; Limb- or life-threatening complications in patients with diabetes can be prevented with an integrated, multidisciplinary approach . Most patients seen in clinical practice are in the early stages of the disease process . Glycemic control retards the progression of neuropathy, which is the most important risk factor for ulceration . Early detection of the loss of protective sensation and implementation of strategies to prevent ulceration will reduce the rates of limb-threatening complications . Clinicians should routinely examine the feet of diabetic patients . Education in foot care, proper footwear, and close follow-up are required to prevent or promptly detect neuropathic injury . If ulceration occurs, removal of pressure from the site of the ulcer and careful management of the wound will allow healing in most cases . The failure to heal despite these measures should prompt a search for associated arterial insufficiency . If infection is present, appropriate antimicrobial therapy combined with immediate surgical intervention, including revascularization when necessary, will increase the chances of saving the limb . With this comprehensive approach, it is possible to achieve the goal of a 40 percent decrease in amputation rates among diabetic patients by the year 2000. FEBS Lett, 1994 Sep 26, 352(2), 197 - 200 Molecular cloning of Bac7, a proline- and arginine-rich antimicrobial peptide from bovine neutrophils; Scocchi M et al.; Bac7 is a 7 kDa proline- and arginine-rich antimicrobial peptide which was purified from bovine neutrophils . We have used PCR to clone the cDNA of Bac7 precursor, a polypeptide of 21,569 Da . This cDNA is highly conserved in the 5' region, with respect to the corresponding region in the precursors of several other structurally unrelated myeloid antimicrobial peptides . Furthermore, a 148 nt non-coding region at the 3' end is 75% homologous to a corresponding region of the cDNA of the precursor of PR-39, a porcine antibacterial peptide which is also proline- and arginine-rich. J Biol Chem, 1994 Sep 23, 269(38), 23661 - 7 Delineation of the glycosaminoglycan-binding site in the human inflammatory response protein lactoferrin; Mann DM et al.; Lactoferrin is an iron-binding protein which is synthesized by mucosal epithelium and neutrophils and released by these cells in response to inflammatory stimuli . It promotes neutrophil aggregation and manifests iron-dependent and -independent antimicrobial properties in vitro . Since lactoferrin binds to glycosaminoglycans (GAGs) and sulfated polysaccharides can inhibit its clearance in vivo and in vitro, we sought to examine its interaction with the GAGs chondroitin sulfate and heparin . Amino-terminal sequencing of proteolytic fragments of human lactoferrin that were fractionated by GAG chromatography suggested that the amino-terminal 6 kDa of the secreted protein mediates its interaction with GAGs . Synthetic peptides were used to show that the first 33 residues of human lactoferrin can bind well to solid-phase or solution-phase GAGs . The first 33 residues bound fluoresceinamine-labeled heparin with an IC50 (611 nM) which approximated that of the intact protein (124 nM) . In contrast, when the first six residues (GRRRRS) were removed from this peptide, it then bound poorly to heparin (IC50 = 49 microM) . Our results suggest that the GRRRRS sequence at the amino terminus of human lactoferrin acts synergistically with an RKVR sequence at positions 28-31 to form the predominate functional GAG-binding site of human lactoferrin . Molecular modeling of the crystalline structure of lactoferrin supports a synergistic activity between these two sites since it shows that they juxtapose each other on the surface of the folded protein . Solid docking calculations indicate that they can form a cationic cradle as a binding site for chondroitin sulfate. J Chromatogr B Biomed Appl, 1994 Sep 23, 659(1-2), 243 - 57 Derivatization reactions applicable to pesticide determination by high-performance liquid chromatography; McGarvey BD; The literature dealing with HPLC analytical methods for pesticides employing derivatization reactions is reviewed . Included are methods for insecticides, acaricides, nematicides, antimicrobials, herbicides and a rodenticide . Derivatization reactions are employed mainly for the purpose of increasing sensitivity or selectivity for the UV or, more frequently, fluorescence detectors . Of the pre-column and post-column derivatization methods reviewed, post-column methods are the more commonly used. J Immunol Methods, 1994 Sep 14, 174(1-2), 185 - 94 Antimicrobial functions of mononuclear phagocytes; Langermans JA et al.; One of the major functions of mononuclear phagocytes, i.e., monocytes and macrophages, is the phagocytosis and killing of microorganisms . To obtain more insight into the pathogenesis of infectious diseases and to develop new therapies against these diseases, a better understanding of the antimicrobial mechanisms employed by mononuclear phagocytes is essential . The present review gives a short description of the mononuclear phagocyte system and summarizes various methods that are used to study the antimicrobial mechanisms of mononuclear phagocytes. Biochemistry, 1994 Sep 13, 33(36), 10951 - 60 Spectrum of antimicrobial activity and assembly of dermaseptin-b and its precursor form in phospholipid membranes; Strahilevitz J et al.; Dermaseptins are 27-34 amino acid antimicrobial peptides that irreversibly inhibit growth of pathogenic filamentous fungi, in addition to their ability to inhibit the growth of bacteria, yeasts, and protozoa . Synthetic peptides, with sequences corresponding to dermaseptin-b (DS-b) and its N-terminal extended precursor form dermaseptin-B (DS-B), were synthesized and investigated with respect to their spectrum of antimicrobial activity and their mode of interaction with model membranes composed of PS or PC/PS phospholipids . We found that DS-B is much more potent than DS-b against all microorganisms tested . Furthermore, despite significant structural identity between DS-b and DS-S (Pouny et al., 1992), only the former is highly effective at inhibiting the growth of filamentous fungi . The peptides were labeled selectively at their N-terminal amino acid with either 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) or rhodamine fluorescent probes, which facilitated the determination of their partition coefficients with phospholipid membranes and their organization in their membrane-bound state . The partition coefficients of DS-B are 10-fold higher than those of DS-b and DS-S, with both acidic and zwitterionic phospholipid vesicles . This may explain the ability of DS-B to permeate both types of vesicles efficiently . Furthermore, while both DS-b and DS-B interact with phospholipid membranes in a noncooperative manner, they are self-associated in their membrane-bound state . This noncooperative binding probably prevents aggregation of the peptides on the surface of outer bacterial membranes, and assists them in efficiently diffusing into the inner target membranes . The exceptional property of DS-B to bind strongly to phospholipid membranes and to form small bundles correlates with its high potential to kill yeast and filamentous fungi . As a molecular model, dermaseptins may be of potential interest in drug design, particularly in antifungal warfare. Ann N Y Acad Sci, 1994 Sep 6, 732, 140 - 51 Doxycycline and chemically modified tetracyclines inhibit gelatinase A (MMP-2) gene expression in human skin keratinocytes; Uitto VJ et al.; The mechanism of tetracycline-induced inhibition of matrix metalloproteinases (MMP) was studied by measuring the MMP secretion and MMP-2 mRNA levels in unkeratinizing periodontal ligament epithelial cells and skin keratinocytes cultured in the presence of doxycycline or chemically modified tetracyclines (CMT) lacking antimicrobial activity . Doxycycline, CMT-1, and CMT-8 exerted a direct dose-dependent inhibition of porcine periodontal ligament epithelial cell medium MMP activity as assayed by gelatin enzymography . Both the 92-kDa (MMP-9) and 72-kDa (MMP-2) gelatinases were inhibited by the tetracyclines added to the conditioned medium . Culturing the cells in the presence of the tetracyclines required considerably smaller concentrations to reduce the secreted MMP activity . The drugs were not toxic to the epithelial cells at concentrations from 4 to 250 micrograms/mL up to 24 h of culture . Tetracycline effects on the MMP-2 mRNA levels were studied in human skin keratinocytes using Northern hybridization analysis with a specific cDNA probe . A marked inhibition in the MMP-2 gene expression was observed by 6 h with 5 micrograms/mL of doxycycline, CMT-1 or CMT-8 . Doxycycline inhibition was somewhat stronger than the two other tetracyclines . After 24 h of culture with 50 micrograms/mL of the drugs, the total RNA levels also decreased by 33 to 40% . The 72-kDa gelatinase activity in culture medium of the keratinocytes followed roughly the pattern of inhibition of the gene expression . We conclude that doxycycline and the chemically modified tetracyclines, in addition to inhibiting the MMP activity may also reduce the enzyme expression at the transcriptional level. J Biol Chem, 1994 Sep 2, 269(35), 22372 - 8 Conversion of vestitone to medicarpin in alfalfa (Medicago sativa L.) is catalyzed by two independent enzymes . Identification, purification, and characterization of vestitone reductase and 7,2'-dihydroxy-4'-methoxyisoflavanol dehydratase; Guo L et al.; Pterocarpan phytoalexins are antimicrobial compounds in leguminous plants . The final step of pterocarpan biosynthesis, conversion of vestitone to medicarpin, was thought to be catalyzed by a single enzyme "pterocarpan synthase." We have shown that the pterocarpan synthase activity observed in crude extracts of alfalfa suspension cell cultures is the sum of two independent enzymatic activities: vestitone reductase, which catalyzes the NADPH-dependent reduction of vestitone to 7,2'-dihydroxy-4'-methoxyisoflavanol (DMI), and DMI dehydratase, which catalyzes loss of water and closure of an ether ring to form medicarpin . The first enzyme, vestitone reductase, was purified 1,840-fold to homogeneity by a 5-step procedure . Purified vestitone reductase showed a single band on SDS-polyacrylamide gel electrophoresis with an estimated molecular mass of 38 kDa . The native molecular mass measured by gel filtration was shown to be 34 kDa, indicating that vestitone reductase is a monomer . Vestitone reductase has strict substrate stereo specificity for (3R)-vestitone with a Km value of 45 microM . The second enzyme, DMI dehydratase, was partially purified 962-fold . DMI dehydratase had a native molecular mass of 38 kDa as estimated by gel filtration and a Km value of 5 microM for DMI . Both enzymes have a temperature optimum of 30 degrees C and a pH optimum of 6.0 . The discovery of vestitone reductase and DMI dehydratase will facilitate future genetic manipulation of pterocarpan biosynthesis. Ann Emerg Med, 1994 Sep, 24(3), 473 - 89 The role of new antibiotics for the treatment of infections in the emergency department; Talan DA; Treatment of infectious diseases comprises a large part of emergency medicine practice . The management of infectious diseases in the emergency department is often different than in other settings because of the types of infectious presentations and the frequent necessity of empiric treatment decisions . This paper examines the new antimicrobials and their role for the treatment of infections in the ED. Ann Emerg Med, 1994 Sep, 24(3), 454 - 6 Emerging problems of antimicrobial resistance; Cohen ML; The incidence of organisms resistant to various antimicrobial agents has risen over the last several years, resulting in an increase in morbidity and mortality and overall treatment costs . The emergence of virtually untreatable infections has focused the medical community's attention on this issue . This paper reviews common pathogens (both nosocomial and community-acquired infections) that have become resistant to antimicrobial drugs . Approaches that may prevent or retard the development, of resistance among these organisms are discussed. Am J Surg, 1994 Sep, 168(3), 239 - 43 Emergent abdominal surgery in AIDS: experience in San Francisco; Whitney TM et al.; Several recent reviews have suggested that aggressive surgical intervention can reduce morbidity and mortality associated with intra-abdominal crises in AIDS patients . We reviewed our experience with 57 AIDS patients with 63 emergent laparotomies performed at 4 hospitals affiliated with the University of California in San Francisco . Fifty-five patients (96%) were homosexual men . Thirty-nine (68%) had been treated for an opportunistic infection . Indications for exploration included right lower quadrant pain consistent with appendicitis in 24 patients (38%), visceral perforation or obstruction in 11 (17%), right upper quadrant pain in 9 (14%), diffuse peritonitis in 8 (13%), and uncontrollable hemorrhage in 8 (13%) . Perioperative mortality was 12% (7/57) . Fifteen patients (26%) suffered major complications including pneumonia, sepsis, multi-organ failure, and intra-abdominal abscess . Forty-five of 50 survivors (90%) were receiving some type of chronic antimicrobial or antineoplastic chemotherapy, compared to only 2 of the 7 patients who died (28.6%) (P < 0.001) . Lack of ongoing prophylactic treatment for AIDS-related disease, active opportunistic infections, Walter Reed VI classification, and ongoing sepsis at the time of exploration were noted to be associated with increased morbidity and mortality. Am J Gastroenterol, 1994 Sep, 89(9), 1505 - 10 Helicobacter pylori and refractory duodenal ulcers: cross-over comparison of continued cimetidine with cimetidine plus antimicrobials; Boyd HK et al.; OBJECTIVES: To determine the distribution of Helicobacter pylori in the antral and duodenal mucosa of patients with duodenal ulcers refractory to 12 wk of treatment with cimetidine and to evaluate the effect of adding antimicrobial agents to cimetidine on the healing of refractory duodenal ulcers . METHODS: A randomized crossover comparison of continued 800 mg of cimetidine at night for 4 wk with cimetidine plus 500 mg of amoxycillin three times a day for the first 2 wk and 250 mg of metronidazole three times a day for the second 2 wk . H . pylori status in the gastric antral and duodenal mucosa was evaluated by histology and bacterial culture before and at the end of each treatment period . RESULTS: Forty-eight patients were studied . Upon entry to the study, all patients had antral colonization with H . pylori . In the duodenum, active chronic duodenitis was present in 66%, duodenal gastric metaplasia in 33%, and H . pylori in 50%, similar proportions to patients with nonrefractory duodenal ulcers . Healing occurred in 70% (30 of 43) of patients during treatment with cimetidine plus antimicrobials but in only 21% (6 of 28) during treatment with cimetidine alone (p = 0.0003) . In patients who received antimicrobials, neither clearance of H . pylori from the antrum (58% of patients) or duodenum (71% of colonized patients) nor eradication of H . pylori (33%) was significantly correlated with ulcer healing . CONCLUSIONS: The distribution of H . pylori in refractory duodenal ulcers is similar to nonrefractory ulcers, and the combination of amoxycillin and metronidazole with cimetidine increases the proportion of refractory duodenal ulcers, which heals. Med Clin North Am, 1994 Sep, 78(5), 997 - 1014 Antibiotics for pneumonia therapy; Mandell LA; When treating any infectious disease, a physician selects an antimicrobial based on the following considerations: the in vitro activity of the drug, its pharmacokinetic properties, the efficacy data based on properly designed and conducted clinical trials, and finally the adverse effects . In this article, all of these factors, with the exception of adverse effects, were discussed . It was neither my intent nor my purpose to deal with side effects or adverse drug reactions because these are well covered in standard texts or physician references such as the Physicians' Desk Reference and the American Hospital Formulary Service (United States) and the Compendium of Pharmaceuticals and Specialties (Canada). Med Clin North Am, 1994 Sep, 78(5), 1185 - 98 Prevention of nosocomial pneumonia; Thompson R; Prevention of nosocomial pneumonia becomes an achievable goal only to the extent that the mechanisms of infection are known . It is likely that there is variation among microorganisms, patients, type of care and intensive care, and practices that determines the relative efficacy of preventive measures . Certain procedures appear to be universally required and include adequate reprocessing of ventilation equipment and infection control measures in patient care . In contrast, many factors may affect the role of the stomach as a cause of nosocomial pneumonia, including enteral feeding procedures and gastric acidity . Differences in results between studies of preventive measures may reflect uncontrolled practice factors, which make the measures either more or less important . Selective decontamination of the digestive tract is a measure with potentially serious consequences, primarily cost and microbial resistance, and should be undertaken with care probably in selected high-risk patients . Other recommendations such as the use of sucralfate, which is effective in prevention of bleeding without clear side effects, are probably worth instituting based on existing evidence . The primary need may be for better reprocessing of equipment or hand washing and sterile gloves, or it may be several changes at once . Certainly an array of preventive measures is necessary, and there is probably no single procedure likely to solve such a complex problem . Use of the collective findings of many investigators needs to be made and strategies applied to each patient and setting . There has been a marked increase in our knowledge of nosocomial pneumonia, and effective measures for prevention are available . Application of these measures widely should reduce the frequency of respiratory complications . The microbiologic tools to compare bacterial isolates have been developed, and the course of events preceding infection of the patient can be demonstrated . The role of equipment, environment, other patients, personnel, colonization sites, and other factors can now be examined . Future studies should control for the many known factors that may predispose to nosocomial pneumonia to make the results meaningful . This would include definition of infection, patient risk factors, identification of microorganisms, details of enteral nutrition, type of stress ulcer prophylaxis, exposure to antimicrobial agents, and institutional resistance patterns . In some studies, surveillance cultures and molecular epidemiology techniques would be required . Large controlled multicenter studies are necessary to determine the significance of the results of promising smaller studies.(ABSTRACT TRUNCATED AT 400 WORDS) Med Clin North Am, 1994 Sep, 78(5), 1143 - 72 The approach to nonresolving pneumonia; Orens JB et al.; Pneumonias that fail to resolve at the expected rate may reflect derangements in host defenses, inadequate or inappropriate antimicrobial therapy, highly virulent pathogens, or myriad noninfectious causes . In this article, noninfectious causes of pulmonary infiltrates mimicking community-acquired pneumonia are discussed . The salient clinical, radiographic, and histopathologic features of diverse immune-mediated syndromes are reviewed, and an approach to diagnosis and therapy of nonresolving pneumonias is presented. Med Clin North Am, 1994 Sep, 78(5), 1123 - 41 An approach to empiric therapy of nosocomial pneumonia; Niederman MS; Because many studies show that antibiotic therapy is effective for nosocomial pneumonia, it is necessary to have an approach to antibiotic selection to reduce mortality . Empiric therapy can be chosen, based on an assessment of patient risk factors for specific organisms and on an evaluation of the severity of illness present . Empiric regimens must be selected from a knowledge of antibiotic pharmacodynamics, as well as from an appreciation of the antimicrobial spectrum of the various antibacterials . When using such an approach, it is necessary to realize the limitations of effective therapy and to evaluate a number of relevant issues if the patient is not improving during treatment. Med Clin North Am, 1994 Sep, 78(5), 1035 - 48 Overview of community-acquired pneumonia . Prognosis and clinical features; Campbell GD; Despite the introduction of newer antibiotics, vaccinations, and better supportive care, CAP remains a common, frequently fatal disease . Age and coexisting illness influence which infectious agents are most likely to cause infection . Severity of illness and clinical features are influenced by various host factors and by the virulence of the infectious agent . Mortality and morbidity are reduced by the rapid institution of appropriate antimicrobial therapy . Because of the limitations of presently available diagnostic tests, many patients are begun on empiric regimens, and in up to half of these individuals, a cause is not identified . Although there are a number of potential pathogens, it is possible to identify likely pathogens based on easily identifiable clinical factors (age, presence of coexisting disease, severity of illness at presentation, and the need for hospitalization) . Using this approach, CAP in immunocompetent adults may be divided into four categories . Once empiric therapy has been initiated, therapy should be continued for at least 72 hours unless clinical deterioration is noted . Within 4 days, fever and leukocytosis should return to baseline, but abnormal physical findings (i.e., crackles) require longer to resolve, especially with coexisting illness, and chest radiographic findings are the last to return to baseline and are especially delayed if the patient is bacteremic or has structural lung disease . Not all patients respond to initial empiric therapy . Reasons for this include antimicrobial resistance, the presence of nonbacterial pathogens (respiratory viruses), unusual bacterial pathogens, noninfectious causes that may mimic CAP, infectious complications (i.e., empyema), and pneumonia occurring in patients with unrecognized severe immunosuppression . Failure to improve after 72 hours and development of deterioration are indications for repeat diagnostic workup and consideration of alternative diagnoses . More invasive diagnostic tests are appropriate in severely ill patients and in those whose condition is deteriorating rapidly. J Infect Dis, 1994 Sep, 170(3), 653 - 8 Experimental evaluation of combined prophylaxis against murine pneumocystosis and toxoplasmosis; Brun-Pascaud M et al.; Prophylactic efficacy of antimicrobial agents against pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats . Corticosteroid-treated rats naturally infected by P . carinii were challenged with the RH strain of T . gondii . Infection was assessed by counting P . carinii cysts in lung and by titration of T . gondii in tissues by tissue culture . Untreated rats died after challenge, with P . carinii infection in lungs and T . gondii infection in liver, spleen, lungs, and brain . In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T . gondii was eradicated and P . carinii pneumonia prevented . Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P . carinii . Atovaquone, 100 or 200 mg/kg, had only partial efficacy against pneumocystosis and toxoplasmosis . These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts. J Neuroimmunol, 1994 Sep, 53(2), 181 - 7 Activation of the hypothalamic-pituitary-adrenal axis differentially affects the anti-mycobacterial activity of macrophages from BCG-resistant and susceptible mice; Brown DH et al.; The effect of hypothalamic-pituitary-adrenal (HPA) axis activation and exogenous glucocorticoids on the ability of splenic macrophages to control the growth of Mycobacterium avium was evaluated . We found that activation of the HPA axis by restraint stress or the addition of corticosterone increased the susceptibility of macrophages from mice that are innately susceptible to the in vivo growth of M . avium . In contrast, the ability of macrophages from innately resistant, congenic mice to control the growth of M . avium was not affected by HPA activation or the addition of corticosterone . The effect of restraint and of corticosterone on macrophage function was abrogated by either treating mice with the glucocorticoid receptor antagonist RU486 or the addition of the drug to cultures of macrophages . Activation of the HPA axis as well as the addition of corticosterone to cultures of macrophages resulted in a suppression of the production of tumor necrosis factor (TNF)-alpha and of reactive nitrogen intermediates by macrophages from both strains of mice . The lack of effect of HPA activation and of corticosterone on the mycobacterial resistance of macrophages from BCG-resistant mice, while at the same time suppressing the production of reactive nitrogen intermediates, appears to rule out a role for this antimicrobial pathway in innate resistance to mycobacterial growth. J Endod, 1994 Sep, 20(9), 445 - 8 Placement of calcium hydroxide in simulated canals: comparison of glycerin versus water; Rivera EM et al.; Calcium hydroxide (Ca(OH)2) is an intracanal medicament used as an antimicrobial agent, temporary obturant, and for apexification . Placement should be controlled for the maximum biological effect . This study evaluated and compared the effectiveness of delivery of Ca(OH)2 mixed with water or with glycerin as to (a) length of placement and (b) density of fill at different levels . Fifty-six simulated canals with moderate curvature were prepared to #60 using the step-back technique . Ca(OH)2 was mixed with either water (28 canals) or glycerin (28 canals) into a thick paste and placed with lentulo spirals . Radiographs were made and blindly assessed . Results showed that glycerin was statistically significantly superior (p < 0.05) to water as to (a) length of fill and (b) density in the coronal, middle, and apical thirds . Of particular interest was the apical third, in which 0% of water and 50% of glycerin Ca(OH)2 pastes were completely dense. Eur Respir J, 1994 Sep, 7(9), 1678 - 89 Pulmonary macrophages; Lohmann-Matthes ML et al.; Interest in pulmonary macrophage research has greatly increased as is now possible not only to work with the easily accessible alveolar macrophages but also with macrophages prepared from lung tissue, such as the interstitial macrophages, dendritic cells and intravascular macrophages . A fascinating aspect is that, in one organ, the modulation of macrophage functions according to their anatomical localization can be studied . This article tries to review some of the modern aspects of research on pulmonary macrophages . These include localization and origin of the various subpopulations, membrane receptors and surface markers, arachidonic acid metabolism, antimicrobial activity, cytokine production and some aspects of macrophage involvement in sarcoidosis and idiopathic lung fibrosis. Compendium . 1994 Sep;15(9):1158, 1160, 1162 passim; quiz 1170. Comparative antimicrobial effectiveness of a substantive (0.12% chlorhexidine) and a nonsubstantive (phenolic) mouthrinse in vivo and in vitro; Briner WW et al.; Antimicrobial mouthrinses can play an important role in maintaining oral health by killing cariogenic organisms and preventing plaque and gingivitis . The active ingredients are adsorbed by oral tissues and then gradually released into the saliva . In this article, the effectiveness of a substantive chlorhexidine and a nonsubstantive phenolic antimicrobial mouthrinse were tested . When compared, the results indicated that the two types of mouthrinses are equally effective at killing salivary microbes for up to 30 minutes after rinsing . The prescriptive substantive rinse, however, continued its microbicidal effect for a longer duration (up to 5 hours) than the over-the-counter nonsubstantive rinse . The substantive rinse showed pronounced and measurable zones of inhibition around each well in the agar diffusion assay where the nonsubstantive rinse showed no zone around any well at any time . The substantive rinse also showed a superior ability to inhibit the growth of 28 oral microbes, including some putative periodontopathogens, which were assayed. Arzneimittelforschung, 1994 Sep, 44(9), 1029 - 31 Synthesis and characterization of some novel substituted benzenesulphonamides of potential hypoglycemic activity; Hanna MA et al.; Two series of substituted benzenesulphonamides (Va-e and VIa-e) have been synthesized from 4-methoxycarbonyl-1-{p-(acetylamino)benzenesulphonylimino}pyridini um ylide (II) with a view to investigate their pharmacological activity . The structure of the synthesized products was inferred from elemental and spectral data . The hypoglycemic effect, antimicrobial activity and toxicity of the possible chemotherapeutic agents were evaluated . Six of these products were effective, when administered at an oral dose of 100 mg/kg b . wt., inducing marked reduction in blood glucose level. Pharmazie, 1994 Sep, 49(9), 681 - 3 Activity of anthraquinonic and naphthoquinonic compounds on oral bacteria; Didry N et al.; The activity of anthraquinonic compounds and naphthoquinones was tested by micromethods against oral bacteria . The more significant results were obtained with naphthoquinones . Plumbagin, juglone and lawsone possess a wide spectrum of activity . The lowest MIC values were observed with plumbagin and the combination of juglone and lawsone results in a synergism against cariogenic bacteria . Among the eight anthraquinonic compounds investigated only rhein showed significant antimicrobial properties . Results obtained could suggest the use of rhein and plumbagin alone or juglone and lawsone combined for treatment of oral infectious diseases. J Laryngol Otol, 1994 Sep, 108(9), 763 - 7 Alterations to the oropharyngeal and nasopharyngeal microbial flora of children after tonsillectomy and adenoidectomy; Manolis E et al.; The oropharyngeal and nasopharyngeal microbial flora of 40 children with chronically hypertrophied and infected tonsils or adenoids, was studied . Twenty of the children were treated by tonsillectomy and 20 by adenoidectomy . Swabs were taken from the surgical field pre-operatively and from the oropharynx or the nasopharynx 10 and 30 days-post-operatively . The swabs were cultured on suitable culture media and identification as well as quantitative estimation of the isolated bacteria, was carried out . Most of the potentially pathogenic bacteria exhibited beta-lactamase production . Interestingly, after surgical treatment, the respective microorganisms were quantitatively reduced and it was observed that their isolation rate was also lower . Furthermore, bacteria considered as normal inhabitants regularly showed an increase in their frequency of isolation despite the fact that a quantitative decrease was in some instances observed . These findings suggest that tonsillectomy and adenoidectomy result in an alteration to the abnormal oropharyngeal and nasopharyngeal microbial flora producing an almost normal one . It appears that, in cases of the failure of antimicrobial treatment, surgical procedures should be seriously considered. Ginecol Obstet Mex, 1994 Sep, 62, 282 - 4 {The efficacy of sulbactam-ampicillin in preventing postoperative infections in gynecology and obstetrics . A comparative open study}; Ahued Ahued R et al.; An open comparative and multicentric trial was carried out to assess the activity of sulbactam ampicillin combination against no treatment, as a prophylactic agent of post-surgical infection in ob-gyn practice . 100 patients were included in the trial and distributed in two groups . sulbactam/ampicillin 0.5/1.0 g, i.v . was administrated during the surgery and the dose was repeated 6 h . later . No cases of post-surgical infection was detected in the group of sulbactam/ampicillin, while 4 cases were observed in the no treatment group . Sulbactam/ampicillin is an effective and well tolerated antimicrobial agent in the prophylaxis of post-surgical infections. Chemotherapy, 1994 Sep-Oct, 40(5), 333 - 6 Enhanced chemiluminescence response of polymorphonuclear leukocytes by new quinolone antimicrobials; Kubo S et al.; Some of the many antimicrobial agents (beta-lactams, macrolides, aminoglycosides, tetracyclines, new quinolones; NQs) were reported to have a bactericidal or bacteriostatic effect cooperating with host defense mechanisms including polymorphonuclear neutrophils (PMNs) . We investigated the effect of new quinolone antimicrobials on chemiluminescence (CL) response of human PMNs . Among many NQs, we chose ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, AM-1155, NM-394, Q-35, Y-26611 and T-3761 . Twenty-five or 100 micrograms/ml of fleroxacin and ofloxacin enhanced luminol-dependent CL response of PMNs up to 1.5-2.0 times compared to the drug free condition . Other antimicrobial agents, however, inhibited CL response . This suggested that fleroxacin and ofloxacin were more efficient in the treatment of bacterial infections with respect to the interaction between antimicrobials and PMNs. J Acquir Immune Defic Syndr, 1994 Sep, 7(9), 931 - 9 Elevated serum calprotectin levels in HIV-infected patients: the calprotectin response during ZDV treatment is associated with clinical events; Muller F et al.; The calcium-binding myelomonocytic protein calprotectin (L1 protein) was quantified in serum from 51 patients with HIV infection and in 20 HIV-seronegative blood donors . Significantly elevated levels were found both in asymptomatic patients and in people with AIDS compared with controls . The calprotectin level was not related to ongoing or recent opportunistic infections . For patients with CD4+ counts above 50 x 10(6)/L, a significant negative correlation was found between serum calprotectin levels and the CD4+ counts . Serial samples from 24 patients during their first year of zidovudine (ZDV) treatment showed a further elevation of serum calprotectin during the first months of ZDV treatment, with a subsequent decline to pretreatment levels . A low calprotectin response during the first 6 months, determined as area under the curve, was associated with the occurrence of at least one AIDS-defining infection during the first year of antiviral treatment . Also, a low calprotectin maximal response during ZDV therapy was associated with short survival . Similar associations were not found for neopterin, beta 2-microglobulin, HIV p24 antigen, or CD4+ or CD8+ lymphocytes in blood . Our findings in a limited number of patients suggest that calprotectin levels may reflect immune activation and other immune mechanisms correlated with enhanced antimicrobial defense induced at least transiently by antiviral treatment. Diagn Microbiol Infect Dis, 1994 Sep, 20(1), 57 - 9 In vitro activity of dirithromycin, a new macrolide antibiotic, against Mycoplasma species; Rennie KA et al.; Dirithromycin is a new macrolide antibiotic that achieves high tissue concentration . We compared its in vitro activity against Mycoplasma species with that of erythromycin and tetracycline . Clinical isolates of M . pneumoniae (40), M . hominis (40), and Ureaplasma urealyticum (40) were tested against serial dilutions of three antibiotics using a microtiter plate method . Minimum inhibitory concentrations (MIC) were read as the lowest concentration of antibiotic yielding no color change in the broth . Neither macrolide antibiotic exhibited antimicrobial activity against M . hominis; MIC50 and MIC90 for tetracycline were 0.6 and 32 micrograms/ml, respectively . MIC50 for U . urealyticum was 4.0 micrograms/ml for dirithromycin, 2.0 micrograms/ml for erythromycin, and 1.0 micrograms/ml for tetracycline . MIC90 for U . urealyticum was > 128 micrograms/ml for all three agents . Against M . pneumoniae dirithromycin exhibited MIC50 of 0.1 micrograms/ml and MIC90 of 0.1 micrograms/ml . Both values for erythromycin were 0.2 micrograms/ml; for tetracycline they were 0.1 and 1.0 micrograms/ml, respectively . These results demonstrate the high in vitro activity of dirithromycin against M . pneumoniae and suggest that this agent may have a role in the treatment of respiratory Mycoplasma infections. J Physiol Pharmacol, 1994 Sep, 45(3), 333 - 50 Role of Helicobacter pylori infection in gastro-duodenal secretion and in pathogenesis of peptic ulcer and gastritis; Konturek PC et al.; Etiologic role for HP appears to be best established in histologically proven gastritis . The major factors mediating gastritis induced by the colonization of the "gastric type" mucosa with HP are probably cytotoxins, cytokines and free radicals activated by this organisms . The deficiency of negative feedback in somatostatin-gastrin link in antral gastritis may result in an excessive gastrin release and increased gastric acid secretion with increased duodenal acid load under basal state and after meal . Recent NIH consensus 1994 proposes that: (1) ulcer patients with HP require treatment with antimicrobial agents whether on first presentation or on recurrence; (2) the value of treatment of HP infection in non-ulcer dyspepsia remains to be determined and (3) the asymptomatic subjects with HP infection do not require treatment with antimicrobial agents. Protein Sci, 1994 Sep, 3(9), 1362 - 73 Interactions between human defensins and lipid bilayers: evidence for formation of multimeric pores; Wimley WC et al.; Defensins comprise a family of broad-spectrum antimicrobial peptides that are stored in the cytoplasmic granules of mammalian neutrophils and Paneth cells of the small intestine . Neutrophil defensins are known to permeabilize cell membranes of susceptible microorganisms, but the mechanism of permeabilization is uncertain . We report here the results of an investigation of the mechanism by which HNP-2, one of 4 human neutrophil defensins, permeabilizes large unilamellar vesicles formed from the anionic lipid palmitoyloleoylphosphatidylglycerol (POPG) . As observed by others, we find that HNP-2 (net charge = +3) cannot bind to vesicles formed from neutral lipids . The binding of HNP-2 to vesicles containing varying amounts of POPG and neutral (zwitterionic) palmitoyloleoylphosphatidylcholine (POPC) demonstrates that binding is initiated through electrostatic interactions . Because vesicle aggregation and fusion can confound studies of the interaction of HNP-2 with vesicles, those processes were explored systematically by varying the concentrations of vesicles and HNP-2, and the POPG:POPC ratio . Vesicles (300 microM POPG) readily aggregated at HNP-2 concentrations above 1 microM, but no mixing of vesicle contents could be detected for concentrations as high as 2 microM despite the fact that intervesicular lipid mixing could be demonstrated . This indicates that if fusion of vesicles occurs, it is hemi-fusion, in which only the outer monolayers mix at bilayer contact sites . Under conditions of limited aggregation and intervesicular lipid mixing, the fractional leakage of small solutes is a sigmoidal function of peptide concentration . For 300 microM POPG vesicles, 50% of entrapped solute is released by 0.7 microM HNP-2 . We introduce a simple method for determining whether leakage from vesicles is graded or all-or-none . We show by means of this fluorescence "requenching" method that native HNP-2 induces vesicle leakage in an all-or-none manner, whereas reduced HNP-2 induces partial, or graded, leakage of vesicle contents . At HNP-2 concentrations that release 100% of small (approximately 400 Da) markers, a fluorescent dextran of 4,400 Da is partially retained in the vesicles, and a 18,900-Da dextran is mostly retained . These results suggest that HNP-2 can form pores that have a maximum diameter of approximately 25 A . A speculative multimeric model of the pore is presented based on these results and on the crystal structure of a human defensin. Clin J Pain, 1994 Sep, 10(3), 218 - 26 Psychological problems in chronic prostatitis patients with pain; Egan KJ et al.; OBJECTIVE: Men with chronic prostatitis are frequently seen in urological practice and are difficult to treat with standard antimicrobial medications . This pilot study was designed to take a different perspective in assessing chronic prostatitis patients with pain by evaluating them using a standard chronic pain clinic psychological approach . DESIGN: Twenty men, 27% of the referred group of patients with chronic prostatitis and pain, completed the MMPI and a structured psychological interview . Their findings were compared to age- and education-matched men seeking treatment for chronic low back pain . SETTING: Data were collected at the Pain Clinic within the Department of Anesthesiology at the University of Washington Medical Center . PATIENTS: Patients were 20 men referred from a urology-based Prostatitis Clinic and 20 men referred to the Pain Clinic for chronic low back pain . RESULTS AND CONCLUSIONS: The two groups differed in the impact of their pain problem on their lives . Prostatitis patients were employed but reported that their symptoms greatly interfered with their sexual/romantic relationships . Back pain patients reported that their pain interfered primarily with work; most of these patients had long-term marital relationships, whereas few prostatitis patients did . Half of the prostatitis patients met criteria for major depression, but back pain patients were more somatically focused, depressed, and anxious . The constellation of relationship problems, disruptions in sexual functioning, levels of depression, along with failure of multiple previous medical treatments in men with chronic prostatitis indicates that continued antimicrobial therapy is unlikely to provide the "cure" these patients seek . Psychological evaluation, couples' counseling, individual counseling, and medications for depression all may play a role in a comprehensive approach to these patients . These results must be considered as preliminary and as representative of a possibly skewed sample of prostatitis patients since only those men who accepted the referral to a pain clinic psychologist for an evaluation were assessed . Clearly, they are likely to be among the patients who are most psychologically and sexually impaired by the chronic prostatitis and associated pain . A further study with less self-selection is indicated. Int J Clin Pharmacol Ther, 1994 Sep, 32(9), 488 - 90 Maternal drug treatment and human milk banking; Hoppu K et al.; We studied prospectively during one year temporary drug use by mothers donating breast milk to assess the problem of drug treatment of donors . Sixty-four of the 284 mothers (22.5%) had to abstain from donating due to medication . The indication was infection in 50/56 treatments (89.3%) . Antimicrobial agents were prescribed 44/52 times (84.6%) . The channelling of milk from mothers in early phases of lactation to premature and newborn infants was identified as a special risk situation, if mothers on medication are not excluded . The limited number of such donors leads to use of milk unpooled or pooled to small volumes with increased risk for adverse effects to babies as a consequence . We recommend a wash-out period of 5 half-lives of the drug after the last ingested dose . For the majority of drugs in this study, with some important exceptions, a wash-out period of 1 day was sufficient. Minerva Stomatol, 1994 Sep, 43(9), 393 - 6 {An in-vitro study of the antimicrobial activity of copper and zinc salts on pure and mixed microbial cultures}; Belcastro S et al.; The authors evaluated the in vitro antimicrobial activity of some copper and zinc salts . The results showed high antimicrobial activity of copper salts versus S . mutans and versus the bacterial association tested in this study. Infect Dis Clin North Am, 1994 Sep, 8(3), 607 - 15 Dermatologic manifestations of antimicrobial adverse reactions with special emphasis on topical exposure; Rietschel RL; Topical application of antimicrobial agents can lead to an increased risk of systemic reactions . Adverse reactions can occur with topical antifungals and antiviral agents in addition to antibiotics. Trends Microbiol, 1994 Sep, 2(9), 324 - 8 Integration of antimicrobial host defenses: role of the bactericidal/permeability-increasing protein; Elsbach P et al.; Our understanding of the complex and integrated host-defense systems against microbial infection has progressed rapidly with the characterization of individual components . However, the various factors must be studied not only in isolation, but also in a closer approximation to the in vivo situation, where these factors interact . This is well illustrated in recent studies of the role of the bactericidal/permeability-increasing protein. Antimicrob Agents Chemother, 1994 Sep, 38(9), 2065 - 72 Study of comparative antipneumococcal activities of penicillin G, RP 59500, erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill methodology; Pankuch GA et al.; Time-kill studies were used to examine the in vitro activities of penicillin G, RP 59500, erythromycin, ciprofloxacin, sparfloxacin, and vancomycin against 10 pneumococci expressing various degrees of susceptibility to penicillin and erythromycin . RP 59500 MICs for all strains were 0.5 to 2.0 micrograms/ml, while erythromycin MICs were 0.008 to 0.06 microgram/ml for erythromycin-susceptible strains and 32.0 to 64.0 micrograms/ml for erythromycin-resistant strains . Strains were more susceptible to sparfloxacin (0.125 to 0.5 microgram/ml) than to ciprofloxacin (0.5 to 4.0 micrograms/ml), and all were inhibited by vancomycin at MICs of 0.25 to 0.5 microgram/ml . Time-kill studies showed that antibiotic concentrations greater than the MIC were bactericidal for each strain, with the following exceptions . Erythromycin was bactericidal for one penicillin-resistant strain at 6 h, with regrowth after 12 and 24 h . Three penicillin-susceptible strains were bacteriostatically inhibited by erythromycin at concentrations greater than or equal to the MIC by 6 h . One penicillin-susceptible strain (penicillin MIC, 0.06 microgram/ml) was bacteriostatically inhibited by penicillin G at 24 h at the MIC or at one-half the MIC; a bactericidal effect was found only with penicillin G at concentrations of > or = 0.25 microgram/ml . At 10 min after inoculation a 1- to 3-log10-unit reduction (90 to 99.9%) in the original inoculum was seen for 6 of 10 strains with RP 59500 at concentrations greater than or equal to the MIC . This effect was not found with any of the other compounds tested . A bactericidal effect was found at > or = 6 h with RP 59500 at concentrations of one-half to one-quarter the MIC in 7 of 10 strains, and a bacteriostatic effect was found in 3 or 10 strains, with regrowth at 24 h . One penicillin-resistant strain was examined by the time-kill methodology at 0, 1, 2, and 3 h . RP 59500 at a concentration equal to the MIC was bactericidal within 1 h, and at a concentration of one-half the MIC it was bactericidal within 3 h . This phenomenon was not seen with the other antimicrobial agents tested . Regrowth of strains at ciprofloxacin concentrations equal to the MIC or at a one-half to one-quarter the MIC was found . For sparfloxacin, three of the four penicillin-susceptible strains and two of four penicillin-resistant strains were bacteriostatically inhibited by 6 h . Bactericidal effects were found at 6, 12, and 24 h with both intermediate-resistant, one penicillin-susceptible, and two penicillin-resistant strains . Complete killing was observed with vancomycin at concentrations greater than MIC . Of the new compounds tested, RP 59500 and sparfloxacin show promise for the treatment of infections caused by penicillin-susceptible and -resistant pneumococci . The clinical significance of rapid killing by RP 59500 remains to be determined. Pediatr Infect Dis J, 1994 Sep, 13(9), 782 - 6 Increasing prevalence of penicillin-resistant pneumococcal infections in children in southern Israel: implications for future immunization policies; Dagan R et al.; Although penicillin-resistant pneumococci (PR-PnC) are recognized as an increasing problem worldwide, data on the prevalence of these strains among pediatric patients are incomplete . The present study was conducted in southern Israel (1) to investigate the frequency of PR-PnC in invasive and middle ear infections in pediatric patients and (2) to assess the impact of resistance on the potential role of the candidate conjugate vaccines in preventing childhood PR-PnC infections . A total of 120 blood or cerebrospinal fluid isolates from 1987 to 1993 and 78 ear isolates from 1992 to 1993 were serogrouped and tested for susceptibility to antibacterial agents . The prevalence of PR-PnC among invasive isolates increased from 16% in the years 1987 to 1991 to 36% in 1992 to 1993 (P = 0.019) . This increase was noted mainly for intermediately resistant strains (minimal inhibitory concentration, 0.12 to 1.0 micrograms/ml) whereas the prevalence of highly resistant strains was 3 and 2% for the 2 periods, respectively . The prevalence of PR-PnC among ear isolates in 1992 to 1993 was 42% . Resistance to other antimicrobial agents (one or more of the following: tetracycline, erythromycin, clindamycin and chloramphenicol) was found in 16 (8%) isolates, and multiple resistance (resistance to > or = 3 antibacterial agents) was found in 9 (5%) isolates . Sixty-five (99%) of the 66 resistant isolates belong to Serogroups 6, 14, 19 and 23 . The prevalence of these 4 serogroups rose from 37% in 1987 to 1991 to 66% in 1992 to 1993 (P = 0.043) . This rise was mainly because of Serogroup 23, the prevalence of which rose from 3% in 1987 to 1991 to 23% in 1992 to 1993 (P < 0.001) . Eighty-five percent of all isolates belonging to Serogroup 23 were resistant to penicillin . Because Serogroups 6, 14, 19 and 23 are among the commonest pediatric pneumococcal strains, the newly developed conjugate pneumococcal vaccines contain these 4 serogroups . The selection of antibiotic-resistant strains has thus led to a change in the spectrum of serotypes causing invasive disease and to a situation of potential increase in vaccine coverage for the proposed pneumococcal conjugate vaccines. J Nat Prod, 1994 Sep, 57(9), 1307 - 9 Two new flavones from Calliandra californica; Encarnacion R et al.; Two new flavones were isolated from the medicinal plant Calliandra californica, 7,2',4',5'-tetramethoxyflavone {1} and 5-hydroxy-7,2',4',5'-tetramethoxyflavone {2} . The structures were determined from spectral evidence and both compounds were synthesized . Compound 2 exhibited antimicrobial activity for two test bacterial strains. Bioorg Med Chem, 1994 Sep, 2(9), 999 - 1006 Amino acids that specify structure through hydrophobic clustering and histidine-aromatic interactions lead to biologically active peptidomimetics; Graciani NR et al.; Acyclic beta-sheet structure can be nucleated in heptapeptides when the 4-(2-aminoethyl)-6-dibenzofuranpropanoic acid residue (1) is flanked in sequence by two His residues, a His residue and a hydrophobic residue or by two hydrophobic residues . Acyclic beta-sheet peptidomimetics having an appropriate sequence have sufficient structural integrity to exhibit antimicrobial activity equivalent to that of gramicidin S. Gac Med Mex, 1994 Sep-Oct, 130(5), 355 - 60 {Beta-lactamase production and the patterns of bacterial resistance, 1988-1991}; Rodriguez Noriega E et al.; The adequate use of antimicrobial agents depends to a great degree on the results obtained from the continuous surveillance of bacterial resistance patterns . In order to determine these resistance patterns of bacterial pathogens responsible for community and nosocomial infections a sentinel surveillance program was started in 1988 . An analysis of both pediatric and adult cases revealed 4942 bacteria isolated from different sites . Most samples from community infections were obtained from out patients seen in the infections disease clinic of the Hospital Civil de Guadalajara . Of the bacteria identified, 3584 were derived from community infections . Of those 1138 were gram positive and 2446 were gram-negative . The study also included 1350 nosocomial isolated of which 509 were gram-positive bacteria and 849 were gram-negative bacteria . Overall the gram-negative bacteria were more frequently Beta-lactamase producers than the gram-positive bacteria . Resistance to beta-lactam antibiotics ranged from 64-100% in gram negative bacteria and from 81.96% in some gram positive bacteria . During the last 2 years the resistance to third generation cephalosporins, imipenem and quinolones in gram-negative bacteria has steadily increased . Only through the continuous surveillance of bacterial resistance and the implementation of programs to combat bacterial resistance will the use of valuable antibiotics be prolonged and the activity of other ones be preserved for future use. J Am Coll Surg, 1994 Sep, 179(3), 305 - 12 Comparison of the effects of commonly used wound agents on epithelialization and neovascularization; Kjolseth D et al.; BACKGROUND: The primary effect sought with most topical wound therapy is antimicrobial . Topical wound agents are thought to promote normal healing by protecting the wound from infection . In this study, we examined the effect of six commonly used topical wound agents (bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on epithelialization and neovascularization in noninfected wounds . For this study, a new wound model was used in which direct visualization and quantification of wound epithelialization and neovascularization were carried out throughout the entire healing process . STUDY DESIGN: We measured the effect which 500 U per g of bacitracin, 0.25 percent of sodium hypochlorite, 0.5 percent silver nitrate, 1 percent silver sulfadiazine, 8.5 percent mafenide acetate, and 10 percent povodione-iodine had on the rate of wound epithelialization and neovascularization . The agents were applied topically to 99 circular full-thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male hairless mouse ears . This model enabled us to visualize and measure directly wound epithelialization and neovascularization repeatedly throughout healing, using intravital video microscopy and computerized digitized planimetry . RESULTS: Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide acetate (n = 14) epithelialized in 7.2 +/- 0.7, 7.1 +/- 0.3, and 7.3 +/- 0.3 days, respectively . This was significantly (p < 0.01) faster than the wounds treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and bacitracin (n = 13) . Wounds treated with povidone-iodine epithelialized the slowest (11.8 +/- 0.55 days) . Wound neovascularization was completed most rapidly in the groups treated with povidone-iodine and silver sulfadiazine (15.0 +/- 0.4 and 15.3 +/- 0.7 days, respectively) . This was significantly (p < 0.05) faster than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4 +/- 0.56 days . One-half of the wounds treated with sodium hypochlorite (eight of 16) did not epithelialize or neovascularize . CONCLUSIONS: The various antimicrobial agents studied in our in vivo model affect wound epithelialization and neovascularization differently . These effects on these two very important aspects of healing should be taken into consideration when indicating a specific agent for treatment of different types of wounds. J Exp Med, 1994 Sep 1, 180(3), 783 - 93 Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major; Stenger S et al.; Previous studies with inhibitors of inducible nitric oxide synthase (iNOS) suggested that high-output production of nitric oxide (NO) is an important antimicrobial effector pathway in vitro and in vivo . Here, we investigated the tissue expression of iNOS in mice after infection with Leishmania major . Immunohistochemical staining with an iNOS-specific antiserum revealed that in the cutaneous lesion and draining lymph nodes (LN) of clinically resistant mice (C57BL/6), iNOS protein is found earlier during infection and in significantly higher amounts than in the nonhealing BALB/c strain . Similar differences were seen on the mRNA level as quantitated by competitive polymerase chain reaction . Anti-CD4 treatment of BALB/c mice not only induced resistance to disease, but also restored the expression of iNOS in the tissue . In situ, few or no parasites were found in those regions of the skin lesion and the draining LN which were highly positive for iNOS . By double labeling experiments, macrophages were identified as iNOS expressing cells in vivo . In the lesions of BALB/c mice, cells staining positively for transforming growth factor beta (TGF-beta), a potent inhibitor of iNOS in vitro, were strikingly more prominent than in C57BL/6, whereas no such difference was found for interleukin 4 or interferon gamma (IFN-gamma) . In vitro, production of NO was approximately threefold higher in C57BL/6 than in BALB/c macrophages after stimulation with IFN-gamma . We conclude that the pronounced expression of iNOS in resistant mice is an important mechanism for the elimination of Leishmania in vivo . The relative lack of iNOS in susceptible mice might be a consequence of macrophage deactivation by TGF-beta and reduced responsiveness to IFN-gamma. Infect Immun, 1994 Sep, 62(9), 3663 - 71 Outer surface lipoproteins of Borrelia burgdorferi stimulate nitric oxide production by the cytokine-inducible pathway; Ma Y et al.; The outer surface lipoproteins of Borrelia burgdorferi, OspA and OspB, stimulate the production of nitric oxide (NO) by murine bone marrow-derived macrophages from BALB/c, C3H/HeN, and C3H/HeJ mice . Gamma interferon (IFN-gamma) caused a three- to fivefold enhancement of this production of NO, and the L-arginine analog N-guanidino-monomethyl L-arginine inhibited it . Activation of transcription of the inducible NO synthase gene in stimulated macrophages was demonstrated by reverse transcriptase rapid PCR . Although IFN-gamma increased the amount of NO produced in macrophage cultures, it did not cause transcription of the inducible NO synthase gene greater than that seen with the Borrelia proteins . OspA and OspB also induced the production of high levels (40 to 150 ng/ml) of IFN-gamma in cultures of macrophages incubated with interleukin-2 (IL-2)-elicited cells from normal (T and NK cells) and scid (NK cells) mice but not in macrophages or IL-2-elicited cells cultured individually . This suggests that OspA stimulated macrophage production of cytokines, which, in turn, stimulated the production of IFN-gamma by NK and T cells . Reverse transcriptase rapid PCR demonstrated that OspA and sonicated B . burgdorferi stimulated production of several inflammatory cytokines in macrophage cultures, including IL-1, IL-6, IL-12, IFN-beta, and tumor necrosis factor alpha . As tumor necrosis factor alpha, IFN-beta, and IL-12 are potent activators of IFN-gamma production by T and NK cells, their presence in these cocultures could be responsible for the IFN-gamma production . Lymphocytes from infected C3H mice also produced IFN-gamma when stimulated with B . burgdorferi; thus, immune cells may also modulate NO responses . The generation of NO during infection with B . burgdorferi may be important, as NO has potent antimicrobial properties . NO can also be involved in pathological inflammatory processes in which its generation is detrimental to the host . Thus, the colocalization of B . burgdorferi lipoproteins, NO-producing cells, and regulatory cytokines may determine the outcome of infection. Am J Hosp Pharm, 1994 Aug 15, 51(16), 2016 - 21 Extended dosage intervals for aminoglycosides; Rodman DP et al.; The rationale for and effectiveness of extended dosage intervals for aminoglycosides are discussed . Aminoglycosides can be given once daily despite an elimination half-life of two to three hours because of the postantibiotic effect (PAE) of these agents . Aminoglycosides have a prolonged PAE against a variety of common gram-negative and gram-positive organisms . Higher serum aminoglycoside concentrations are associated with longer PAEs and increased bactericidal activity . Once-daily administration may reduce the potential for adaptive postexposure resistance by allowing less contact time between organism and drug . A major concern with aminoglycosides is the risk of nephrotoxicity and ototoxicity . The uptake of specific aminoglycosides by renal cortical cells is saturable; a longer dosage interval may decrease the risk of nephrotoxicity because higher transient serum aminoglycoside levels appear to be less nephrotoxic than lower but more persistent serum concentrations . Once-daily administration may reduce the risk of ototoxicity through a similar mechanism . An increasing number of clinical trials suggest tht once-daily administration of aminoglycosides and regimens involving shorter dosage intervals are equally effective in patients with normal renal function and gram-negative infections and that once-daily administration may reduce the frequency of toxicity or delay it . Patients with renal dysfunction or neutropenia may also benefit from once-daily administration . Most trials have been small, and in some of them other antimicrobials were given concurrently . Although more study is needed, the evidence to date suggests that once-daily administration of aminoglycosides is as effective as traditional regimens entailing shorter dosage intervals and may reduce the potential for toxicity. Pharmacoeconomics, 1994 Sep, 6(3), 249 - 69 Ceftriaxone . A pharmacoeconomic evaluation of its use in the treatment of serious infections; Davis R et al.; Ceftriaxone possesses a broad spectrum of antimicrobial activity that includes the Gram-positive and Gram-negative aerobes commonly associated with serious infections . Its therapeutic efficacy is comparable to that of other third-generation cephalosporins and aminoglycoside-combination regimens . The most commonly reported adverse events with ceftriaxone are similar in incidence and severity to those reported with other third-generation cephalosporins . Notably, the drug has a favourable pharmacokinetic profile which allows once-daily administration . In comparative studies with other parenteral regimens requiring 3 to 6 daily doses, treatment with once-daily ceftriaxone reduced total antimicrobial drug costs (i.e . acquisition, preparation and administration costs) by 17 to 52% . Ceftriaxone was also more cost effective than ceftazidime and a variety of other antimicrobial treatment regimens (penicillins, cephalosporins, combination regimens) in the treatment of patients with community-acquired pneumonia or bronchopneumonia . This reflected lower drug and hospitalisation costs associated with a reduced length of hospital stay in ceftriaxone recipients . In noncomparative studies, ceftriaxone achieved considerable hospitalisation cost savings in patients with serious infections (mostly bone, joint, skin/skin structure infections), who were able to receive all or part of their antimicrobial therapy as outpatients . In one analysis which evaluated all direct and indirect costs (such as training programmes, transportation, time for visits and supplies) and benefits (such as hospitalisation cost savings, return to work or school, increased productivity) of outpatient ceftriaxone therapy, the overall benefit-cost ratio was approximately 5:1 . The studies to date confirm that ceftriaxone is effective, well tolerated, convenient to administer and, when utilised appropriately, offers the potential for cost avoidance in patients with serious infections . Although additional well designed pharmacoeconomic analyses are needed to further evaluate its cost effectiveness, ceftriaxone should be considered an essential third-generation cephalosporin formulatory representative in most clinical settings. Pharmacoeconomics, 1994 Sep, 6(3), 202 - 14 Therapy of acute otitis media . Clinical and economic aspects; Sagraves R et al.; Acute otitis media is a common health problem worldwide that accounts for significant morbidity, primarily among pre-school-age children, for which antimicrobial therapy is currently the treatment of choice . Approximately 25% of all prescriptions written in the US for children under the age of 10 years are for children diagnosed as having acute otitis media . Until adequately designed studies with appropriate patient populations are conducted, clinicians must base their decisions to treat acute otitis media with antimicrobial therapy, and their choice of drug, on local susceptibility patterns (if known), in vitro and in vivo studies, adverse effect profiles, tolerability, and affordability . Such studies will hopefully answer questions about selecting an antimicrobial for acute otitis media and address the comprehensive cost of using various antimicrobials for the condition . Because of the human and economic costs associated with acute otitis media, healthcare practitioners should also be aware of the epidemiology, pathophysiology and various treatment options for children with acute otitis media. Biochem Pharmacol, 1994 Aug 3, 48(3), 613 - 6 Antileishmanial actions of tricyclic neuroleptics appear to lack structural specificity; Evans AT et al.; There is continuing interest in the antimicrobial effects of tricyclic neuroleptics and antidepressants, particularly against trypanosomatid protozoa, but few studies have attempted to dissociate antiparasitic actions from effects on the central nervous system . In this report, we have measured the antileishmanial potency of a range of structural analogues in this drug group, and conclude that no one structural determinant is critical for activity . Instead, potency may be predicted from an overall determination of the lipophilic and steric components of the structure by a simple combination of two descriptive parameters, valence connectivity and an interactive term. Eur J Immunogenet, 1994 Aug, 21(4), 231 - 8 The inducible form of nitric oxide synthase (NOS2) isolated from murine macrophages maps near the nude mutation on mouse chromosome 11; Mock BA et al.; Nitric oxide synthase has been shown to mediate streptozocin-induced diabetes and to act as an antimicrobial agent in murine macrophages . Using a cDNA probe for the inducible form of nitric oxide synthase (Nos2) isolated from murine macrophages we have determined that the gene maps within 1 cM of the nude mutation on mouse Chromosome 11 . The position of Nos2 was also mapped relative to the markers 115, Evi2, Cchlbl (previously unmapped), and Gfap . This map location is discussed relative to map locations for disease susceptibility loci involved in mediating cutaneous leishmaniasis (ScII) and autoimmune type-I diabetes (Idd4). Ann Hematol, 1994 Aug, 69(2), 73 - 7 Localization of human neutrophil peptide (HNP) and its messenger RNA in neutrophil series; Date Y et al.; Human neutrophil peptides (HNPs) 1,2 and 3, also called defensins, have high antimicrobial activity and are cytotoxic to both normal and transformed human cells . The localization of HNPs 1-3 and their mRNAs in cells of normal human bone marrow and peripheral blood was investigated . Immunoreactivity for HNPs 1-3 appeared in the promyelocyte stage and increased with the maturation of the neutrophil series . HNPs 1-3 were absent from such mononuclear phagocyte systems as peripheral monocytes, alveolar macrophages, and Kupffer cells in the liver . HNP 1-3 mRNAs were detected in bone marrow cells by Northern blot analysis and in peripheral leukocytes by the reverse transcription-polymerase chain reaction (RT-PCR) . HNPs 1-3 are restricted to cells of neutrophil lineage and seem to function as microbicidal agents in the neutrophil-mediated defense system. J Nutr, 1994 Aug, 124(8 Suppl), 1455S - 1460S Dietary management of acute diarrheal disease: contemporary scientific issues; Brown KH; Contemporary issues in the dietary management of children with acute diarrhea include the optimal timing of introduction of foods during illness, the appropriate use of milk-containing treatment regimens and mixed diets containing common staple foods, and the proper use of specific micronutrient supplements . Results of recent clinical trials indicate that children should be fed continuously during illness with their usual diets . Most young children fed exclusively with non-human milks can continue to consume these products . However, the subgroup of patients with more severe diarrhea and dehydration may have a slightly increased rate of complications and would, therefore, benefit from close supervision or a modification of their diet . Breastfed infants should continue to nurse at the breast during diarrhea . Treatment of anorexia consists of correction of the underlying metabolic derangements and antimicrobial therapy when indicated . Despite the previous focus of dietary management during diarrhea, attention to convalescent feeding is also necessary to assure complete nutritional recovery following illnessPIP: This paper was presented as a part of a symposium given at the 1993 Experimental Biology Meeting, co-sponsored by the American Institute of Nutrition and the American Society for Clinical Nutrition . In addressing acute diarrheal disease in children younger than 5 years of age, this paper focused primarily on the dietary management aspects in that group . Most previous efforts concerning acute diarrhea have focused on rehydration of the patients with solutions containing glucose, carbohydrates, and key electrolytes . Nutritional aspects have only recently been recognized to be of significant importance in the treatment of acute diarrheal children . Diarrhea prevalence has a direct impact in children's growth . By using improved approaches in treating acute diarrhea, and thereby reducing the negative impact of nutritional complications, including nutritional loss, growth can be maintained even during times of illness . In this study, a regime of continuous feeding therapy immediately following rehydration therapy resulted in no loss in a child's growth rate, while delaying food therapy was associated with weight loss . It was also concluded that lactose-containing milk diets may be used, especially in cases of mild diarrhea . However, cases of severe lactose intolerance were found to contribute to further physiological complications and delayed health recovery . Breast-fed infants, it was concluded, could continue to breast feed, as they showed little intolerance problems . Improving and stressing continuous and proper nutrition during illness-free periods is very important for normal growth, improving resistance to disease agents, and in reducing the future negative impact of acute diarrheal episodes . J Am Dent Assoc, 1994 Aug, 125 Suppl 2, 23S - 28S Antimicrobial mouthrinses: impact on dental hygiene; DeVore LR; Within the assessment, planning, implementation, and evaluation phases of the dental hygiene process of care model, the hygienist can decide which antimicrobial mouthrinse is best suited for a patient's given periodontal condition . First, the initial periodontal condition and the home care of the patient is assessed . Next, the hygienist can plan which protocol, in-office and/or at-home, will best meet the needs of the patient . Implementation of a program can include antimicrobial mouthrinses as an adjunct to scaling and root planing in the office, and the mechanical removal of plaque at home . Finally, the hygienist can evaluate the concerted efforts of both patient and clinician . Patients with extensive crowns and bridges, implants, and orthodontics can also benefit from the use of antimicrobial mouthrinses. J Am Dent Assoc, 1994 Aug, 125 Suppl 2, 11S - 19S Evaluation of antimicrobial mouthrinses and their bactericidal effectiveness; Fine D; The mechanisms of action of antimicrobials have been based in the past on in vitro data obtained from laboratory experiments performed on pure cultures of bacteria . A more complete understanding of oral antimicrobials and their mechanisms of action will results from testing of agents in systems that more closely resemble environmental areas existing in the oral cavity . It is proposed that mechanisms of drug action be studied with a drug held at suboptimal (sublethal) concentrations for short periods and in a dynamic environment that resembles the mouth . Adequate guidelines provided by the American Dental Association Council on Dental Therapeutics are available and have helped to determine the efficacy of these agents over long periods in appropriate populations. J Am Dent Assoc, 1994 Aug, 125(8), 1080 - 7 Evaluating surgical, non-surgical therapy in periodontic patients; Sigurdsson TJ et al.; Eleven highly susceptible periodontitis patients volunteered for a one-year prospective study of surgical and non-surgical periodontal therapy . The patients had high oral hygiene standards and had not received antimicrobial therapy within six months . This study suggests that both types of therapy are equally effective in treating recurrent lesions. Emerg Med Clin North Am, 1994 Aug, 12(3), 863 - 81 Antibiotic use in prosthetic device infections; Rodgers KG; The incidence of prosthetic infections presenting to the emergency department is constantly increasing as the number of patients with prostheses grows . Our first duty as emergency physicians is to maintain a high index of suspicion for prosthetic infection in patients presenting with prosthetic dysfunction or fever . Optimal cultures must be obtained before instituting antimicrobial therapy . In stable patients, this may preclude starting antibiotics in the emergency department . The diversity of prosthetic infections and the need for accurate treatment in order to reduce the morbidity, mortality, and economic costs requires an in-depth knowledge of the microbiology and pharmacologic management of such infections . Except in the case of prosthetic heart valves, prophylactic antibiotics are rarely indicated and their use should be based on judicious clinical decision making. Am J Gastroenterol, 1994 Aug, 89(8), 1203 - 5 Clarithromycin, tetracycline, and bismuth: a new non-metronidazole therapy for Helicobacter pylori infection; al-Assi MT et al.; OBJECTIVE: Metronidazole resistance has become an increasing problem that has limited the usefulness of the original triple therapy . Our objective was to evaluate clarithromycin, a new macrolide compound active against Helicobacter pylori . METHODS: We evaluated a new clarithromycin triple therapy for H . pylori infection consisting of the combination of clarithromycin (500 mg t.i.d.), tetracycline (500 mg q.i.d.), and bismuth subsalicylate tablets (2 q.i.d.) for 14 days . Patients with ulcer also received concomitant ranitidine, 300 mg after the evening meal, for 6 wk . RESULTS: Thirty men with documented H . pylori infection were studied; 29 had peptic ulcer disease . Seven had previously failed antimicrobial therapy, including three with metronidazole-based triple therapy . H . pylori status was determined by histology . H . pylori status and ulcer status were evaluated 4 wk after the end of antimicrobial therapy . The ulcer was healed in 90% . The H . pylori infection was cured in 93%, including all three patients who previously failed metronidazole-based triple therapy . CONCLUSION: We conclude that the combination of clarithromycin, tetracycline, and bismuth is an effective new therapy for treatment of H . pylori infection. Infect Immun, 1994 Aug, 62(8), 3197 - 205 Inhibition of Legionella pneumophila growth by gamma interferon in permissive A/J mouse macrophages: role of reactive oxygen species, nitric oxide, tryptophan, and iron(III); Gebran SJ et al.; A/J mouse macrophages infected with Legionella pneumophila and treated with gamma interferon (IFN-gamma) in vitro developed potent antimicrobial activity . This antilegionella activity was independent of the macrophage capacity to generate reactive oxygen intermediates, since the oxygen radical scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on the antilegionella activity of IFN-gamma-activated macrophages . Likewise, whereas the ability of IFN-gamma-activated macrophages to synthesize reactive nitrogen intermediates was markedly inhibited by the L-arginine (Arg) analogs, NG-monomethyl-L-arginine and L-aminoguanidine, as well as by incubation in L-Arg-free medium, their ability to inhibit the intracellular growth of L . pneumophila remained intact . The intracellular growth of L . pneumophila in A/J macrophages was inhibited by the iron(III) chelator desferrioxamine and reversed by Fe-transferrin as well as by ferric salts . Additionally, IFN-gamma-activated macrophages incorporated 28% less 59Fe(III) compared with nonactivated cells . Nonetheless, only partial blocking of growth restriction was observed when IFN-gamma-stimulated macrophages were saturated with iron(III) . Indole-propionic acid, which appears to inhibit the biosynthesis of L-tryptophan (L-Trp), was an L-Trp-reversible growth inhibitor of L . pneumophila in macrophages, implying that the intracellular replication of this pathogen is also L-Trp dependent . However, an excess of exogenous L-Trp did not reverse the growth inhibition due to IFN-gamma, though a small synergistic effect was observed when the culture medium was supplemented with both iron(III) and L-Trp . We conclude that IFN-gamma-activated macrophages inhibit the intracellular proliferation of L . pneumophila by reactive oxygen intermediate- and reactive nitrogen intermediate-independent mechanisms and just partially by nutritionally dependent mechanisms . We also suggest that additional mechanisms, still unclear, may be involved, since complete reversion was never obtained and since at higher concentrations of IFN-gamma, iron(III) did not induce any significant reversion in the L . pneumophila growth inhibition. J Infect Dis, 1994 Aug, 170(2), 457 - 60 Nitric oxide production and neurotoxicity mediated by activated microglia from human versus mouse brain; Peterson PK et al.; Recent studies indicate that human macrophages lack a high-output inducible nitric oxide synthase (NOS) antimicrobial system . In the present study, microglial cells derived from fetal human versus neonatal mouse brain were compared in a coculture assay of human and murine neuronal cell injury . Neurotoxicity (reflected by lactate dehydrogenase release and impaired neuronal uptake of {3H} gamma-amino butyric acid) and nitric oxide (NO) production (assessed by measurement of nitrite) were observed only in cocultures containing interferon (IFN)-gamma-lipopolysaccharide (LPS)-stimulated murine microglia . Cultures of purified human fetal microglia, however, did produce low levels of NO upon stimulation with IFN-gamma-LPS . These findings support the proposal that human macrophages have an inefficient IFN-gamma-inducible NOS and suggest that in tissues, such as brain, this deficiency could be advantageous for neighboring cells. J Immunol, 1994 Aug 1, 153(3), 1238 - 45 Nitric oxide-independent killing of Francisella tularensis by IFN-gamma-stimulated murine alveolar macrophages; Polsinelli T et al.; Alveolar macrophages (AMs) were analyzed for ability to support replication of the intracellular bacterium Francisella tularensis live vaccine strain (LVS) . AM supported in vitro growth (2 to 3 logs over 5 days) of LVS with a doubling time of 8 +/- 0.8 h . AMs were analyzed for responsiveness to rIFN-gamma for destruction of this lung pathogen . AM treated with 50 U/ml rIFN-gamma allowed early growth of bacteria (six doublings over 48 h) but between 48 and 96 h rIFN-gamma-treated AM eliminated 1.5 logs of LVS . AMs were sensitive to effects of rIFN-gamma; as little as 5 U/ml rIFN-gamma stimulated AM antimicrobial activity, with half-maximal activity 0.3 U/ml . rIFN-gamma-induced antimicrobial effects in AM correlated with amount of nitrites produced, but nitric oxide played only a minimal role in antibacterial effects induced in AM, because NG-MMLA (specific inhibitor of L-arginine-dependent nitric oxide production) failed to block antimicrobial activity of IFN-gamma-stimulated AM . IL-10, TGF-beta 1, and IFN-alpha (cytokines known to regulate effector functions of activated macrophages) also did not block anti-F . tularensis activity of IFN-gamma-stimulated AM . Reactive oxygen metabolites, depletion of tryptophan, and sequestration of iron did not contribute to anti-F . tularensis activity because addition of superoxide dismutase or catalase, excess iron, or tryptophan to IFN-gamma-treated AM did not reverse the anti-F . tularensis activity observed in these cells . Regulation of AM effector activity differed from that of other macrophage populations, in that while rIFN-gamma-stimulated AM produced TNF-alpha (100 U/ml at 72 h), TNF-alpha was not required as a costimulator for induction of antimicrobial activities by rIFN-gamma because anti-TNF-alpha treatment of rIFN-gamma-stimulated AM blocked TNF-alpha but had no effect on either production of nitrites or anti-F . tularensis activity. Intensive Care Med, 1994 Aug, 20(7), 522 - 8 Management of deep Candida infection in surgical and intensive care unit patients . British Society for Antimicrobial Chemotherapy Working Party; Life-threatening infections occurring more than 3 months after BMT . 18 UK Bone Marrow Transplant Teams; LRF Centre for Adult Leukaemia, Royal Postgraduate Medical School, Hammersmith Hospital, London, UKWe sent a questionnaire to 22 teams performing allogeneic and autologous bone marrow transplants (BMT) in the UK enquiring about routine use of prophylactic antimicrobials post-transplant, use of CMV-negative blood products and the incidence of major infection acquired more than 3 months post-BMT . Eighteen centres (82%) responded . To prevent Pneumocystis infection 17 centres routinely gave cotrimoxazole at various doses for periods varying between 3 and 12 months (or sometimes longer if chronic GVHD was present) and six centres gave nebulised pentamidine to patients intolerant of cotrimoxazole . Six centres gave penicillin for 1-3 years to allograft patients . Thirteen centres gave only CMV-negative blood products to CMV neg/neg patients, one centre gave CMV immunoglobulin and five centres continued acyclovir to 6 months . During the period 1986-90, 818 autologous and 1007 allogeneic BMT patients were reported, of whom 113 (6.2%) developed severe infections requiring readmission to hospital . The commonest infections were CMV (n = 19), Pneumocystis (n = 12), Pneumococcus (n = 15), Pseudomonas (n = 7) and Aspergillus (n = 8) . Some patients with severe infections were not receiving 'appropriate' prophylaxis . Only two of the patients with Pneumocystis were taking cotrimoxazole . We conclude that the duration of continuing prophylaxis against Pneumocystis and pneumococcal infections after BMT needs careful consideration; prophylaxis may be especially important in patients with persisting immune suppression. J Ethnopharmacol, 1994 Aug, 44(1), 19 - 24 Extracts and fractions of Thymus capitatus exhibit antimicrobial activities; Kandil O et al.; Preliminary phytochemical screening of the plant Thymus capitatus exhibited the presence of saponins, resins, flavonoids, essential and fixed oils . Aqueous and ethanolic extracts (10-200 mg/ml) as well as saponin, resin and essential oil of the plant (10-5000 micrograms/ml inhibited the growth of several bacteria and fungi. J Clin Microbiol, 1994 Aug, 32(8), 1846 - 9 Evaluation of Etest for rapid susceptibility testing of Mycobacterium chelonae and M . fortuitum; Hoffner SE et al.; Etest is a new concept for MIC determinations for antimicrobial agents that is based on a predefined antibiotic gradient on a plastic strip calibrated with a continuous logarithmic MIC scale covering 15 twofold dilutions . Etest was compared with a reference agar dilution method for susceptibility testing of clinical isolates of Mycobacterium chelonae and M . fortuitum . Results read after 3 days showed good agreement between MICs obtained with Etest and those obtained with the reference method within +/- 2 dilutions for 90% of all test combinations . All but one of the strains were inhibited by low concentrations of ciprofloxacin or amikacin . Susceptibility to clarithromycin, erythromycin, imipenem, rifampin, doxycycline, and fusidic acid was variable, and all strains were resistant to ceftazidime and trimethoprim . The results suggest that Etest is well suited for studies of drug resistance in rapidly growing mycobacteria. Aliment Pharmacol Ther, 1994 Aug, 8(4), 453 - 6 Clarithromycin-amoxycillin therapy for Helicobacter pylori infection; al-Assi MT et al.; BACKGROUND: More convenient therapies are needed to treat Helicobacter pylori infection successfully . Clarithromycin and amoxycillin are effective against H . pylori both in vivo and in vitro . Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H . pylori infection . METHODS: We tested the combination of clarithromycin 500 mg t.d.s . with meals plus amoxycillin 750 mg t.d.s . with meals for 10 days for its effect on H . pylori infection in 29 patients with documented H . pylori peptic ulcers . There were 27 men and 2 women, ranging in age from 23 to 77 years . H . pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy . For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks . H . pylori status was determined by CLOtest and histology . RESULTS: H . pylori infection was cured in 86% (95% CI = 78-99%) . Compliance averaged 93% by pill count . Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects . CONCLUSION: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H . pylori infections. Contraception, 1994 Aug, 50(2), 185 - 90 Synergistic spermicidal activity of neem seed extract, reetha saponins and quinine hydrochloride; Garg S et al.; In order to identify potent spermicidal agents which are free from the side effects of currently available agents, spermicidal activity of purified neem seeds extract (Praneem), reetha saponins and quinine hydrochloride was studied individually and in combination . Sander-Cramer test was used to assess the activity on human sperm . Under the test conditions, minimum effective spermicidal concentrations for Praneem, reetha saponins and quinine hydrochloride were 25%, 0.05% and 0.346%, respectively . At these concentrations, 100% of the sperm were immobilised within 20 seconds . A positive synergistic effect in the spermicidal activity of these components, if used in combination, was observed which implies the use of reduced concentrations of each to bring about the desired action . The selected combination formulated into a suitable dosage form is likely to offer dual benefit of a potent contraceptive and an antimicrobial preparationPIP: Contraceptive researchers in India and the United States used a modified version of the Sander-Cramer test to measure the minimum concentration of purified neem seeds extract, reetha saponins (pericarp of Sapindus fruits), and quinine hydrochloride to kill all sperm within 20 seconds . They wanted to determine the individual and combined action of these potential spermicidal agents on sperm motility and survival . The concentrations needed to effect the death of 100% of human sperm within 20 seconds were 25% for neem oil, 0.05% for reetha saponins, and 0.346% for quinine hydrochloride . A mixture of 25% neem extract, 1% reetha saponins, and 0.75% quinine hydrochloride was spermicidal up to a dilution of 72 times . This dilution was much higher (p = .0004) than the highest spermicidal dilution attained by reetha saponins, the most potent component of the mixture . The positive synergistic effect in the spermicidal activity of these components