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Rev Hosp Clin Fac Med Sao Paulo, 1993 Mar-Apr, 48(2), 69 - 75 {Local treatment of burns: analysis of the use of antimicrobial agents}; Mariani U et al.; The authors studied the local treatment of burns in 11045 cases: 6063 (54.9%) were treated without topical antibacterials and 4985 (45.1%) with antibacterial agents . In 62.1% of cases the topical antibacterial treatment was done mainly in the hospital ward (69.5%) while the treatment without topical medication was mostly performed in the operating room . The use of topical antibacterials was studied during eight years, from 1985 to 1992 . In the earlier periods the justifications were not related to burn wound sepsis . In the recent years the topical antibacterials were used chiefly for the treatment and prophylaxis of wound infection (96.8% of cases). Pediatr Pathol, 1993 Mar-Apr, 13(2), 127 - 32 Vasculitis as a cause of diarrhea and gastrointestinal hemorrhage: a case report; Kotiloglu E et al.; A 13-year-old girl was hospitalized for fever, malaise, intractable diarrhea, and intermittent gastrointestinal hemorrhage . Despite aggressive antimicrobial and supportive treatment, she died with massive bleeding from the upper gastrointestinal tract . Autopsy study revealed systemic polyarteritis nodosa of classic form in the right lung and gastrointestinal tract and of microscopic form in kidneys. Zh Mikrobiol Epidemiol Immunobiol, 1993 Mar-Apr, (2), 32 - 8 {The effect of different antimicrobial preparations on the normalization of the intestinal microflora in patients with disseminated peritonitis}; Levanov AV et al.; These investigations revealed that the treatment of patients with generalized peritonitis with ampiox, gentamicin and metronidazole, as well as with cephalosporins and metronidazole, led to the aggravation of dysbiotic disturbances in normal intestinal microflora, observed in these patients before treatment . Ciprofloxacin had a selective decontaminating effect on the intestine, which facilitated the decrease of suppuration in postoperative wounds. Br J Biomed Sci, 1993 Mar, 50(1), 31 - 4 Antimicrobial susceptibility testing: are we wasting our time? Greenwood D. Routine susceptibility testing of bacterial pathogens has been seen as one of the most important functions of diagnostic microbiology laboratories, but there are powerful arguments both for and against providing such a routine service . Much testing that is carried out does not contribute directly to patient management, since modern agents are usually reliably active and treatment has normally been started successfully before the result is available . Moreover, laboratory tests are so far removed from clinical reality as to be of doubtful value . On the other hand, prescribers still demand the service and there are cogent epidemiological reasons for carrying out the tests . Laboratories also have a crucial role in guiding antibiotic use and in reinforcing local prescribing policies, and routine testing helps to identify the laboratory as the source of expertise and advice . The relationship between the laboratory and its users is changing and microbiologists need to re-assess the service they provide . Many of the benefits of routine susceptibility tests would be retained if periodic surveys of the local prevalence of resistance were carried out, reserving individual testing for the seriously ill and those presenting problems of management. Scanning, 1993 Mar-Apr, 15(2), 67 - 80 Microwave-accelerated cytochemical stains for the image analysis and the electron microscopic examination of light microscopy diagnostic slides; Hanker J et al.; Recent studies in our laboratories have shown how microwave (MW) irradiation can accelerate a number of tissue-processing techniques, especially staining, to aid in the preparation of single specimens on glass microscope slides or coverslips for examination by light microscopy (and electron microscopy, if required) for diagnostic purposes . Techniques have been developed, which give permanently stained preparations, that can be studied initially by light microscopy, their areas of interest mapped, and computer-automated image analysis performed to obtain quantitative information . This is readily performed after MW-accelerated staining with silver methenamine by the Giammara-Hanker PATS or PATS-TS reaction . This variation of the PAS reaction gives excellent markers for specific infectious agents such as lipopolysaccharides for gram-negative bacteria or mannans for fungi . It is also an excellent stain for glycogen and basement membranes and an excellent marker for type III collagen or reticulin in the endoneurium or perineurium of peripheral nerve or in the capillary walls . Our improved MW-accelerated Feulgen reaction with silver methenamine for nuclear DNA is useful to show the nuclei of bacteria and fungi as well as of cells they are infecting . Improved coating and penetration of tissue surfaces by thiocarbohydrazide bridging of ruthenium red, applied under MW-acceleration, render biologic specimens sufficiently conductive for SEM so that sputter coating with gold is unnecessary . The specimens treated with these highly visible electron-opaque stains can be screened with the light microscope after mounting in polyethylene glycol (PEG) and the structures or areas selected for EM study are mapped with a Micro-Locator slide . After removal of the water soluble PEG the specimens are remounted in the usual EM media for scanning electron microscopy (SEM) or transmission electron microscopy (TEM) study of the mapped areas . By comparing duplicate smears from areas of infection, such as two coverslips of buffy coat smears of blood from a patient with septicemia, the microorganisms responsible can occasionally be classified for antimicrobial therapy long before culture results are available; gram-negative bacteria are positive with the Giammara-Hanker PATS-TS stain, and gram-positive bacteria are positive with the SIGMA HT40 Gram stain . The gram-positive as well as gram-negative bacteria are both initially stained by the crystal violet component of the Gram stain . The crystal violet stain is readily removed from the gram-negative (but not the gram-positive) bacteria when the specimens are rinsed with alcohol/acetone . If this rinse step is omitted, the crystal violet remains attached to both gram-negative and gram-positive bacteria . It can then be rendered insoluble, electron-opaque, and conductive by treatment with silver methenamine solution under MW-irradiation . This metallized crystal violet is a more effective silver stain than the PATS-TS stain for a number of gram-negative spirochetes such as Treponema pallidum, the microbe that causes syphilis. FEBS Lett, 1993 Feb 15, 317(3), 255 - 8 Chemotactic and protease-inhibiting activities of antibiotic peptide precursors; Verbanac D et al.; We have recently shown that two antimicrobial peptides (Bac5 and Bac7) and/or their immature forms (proBac5 and proBac7) can be released extracellularly from activated neutrophils . In the present study we have investigated the biological activities of the immature forms, which do not exhibit antimicrobial effects . We show that proBac7 is a monocyte-selective chemoattractant, potentially contributing to the recruitment of these cells to infection sites, whereas proBac5 efficiently inhibits the in vitro activity of cathepsin L, a cysteine proteinase thought to contribute to tissue injury in inflammation. Arch Intern Med, 1993 Feb 8, 153(3), 368 - 72 Clarithromycin and other antimicrobial agents in the treatment of disseminated Mycobacterium avium infections in patients with acquired immunodeficiency syndrome; Dautzenberg B et al.; BACKGROUND: Disseminated infection with Mycobacterium avium is common with late-stage acquired immunodeficiency syndrome (AIDS), and no antimicrobial agent has been found to be clearly effective . METHODS: A multicenter open trial was conducted to assess the antimicrobial activity and clinical efficacy of clarithromycin--a new macrolide antibiotic--against disseminated M avium in 77 patients with late-stage AIDS . Blood cultures were taken at baseline and during treatment; side effects were also evaluated . RESULTS: Mycobacterium avium was eradicated from blood cultures in 11 (63%) of 16 evaluable patients receiving daily doses or 500 or 1000 mg, (n = 21) and in 45 of 46 (98%) of those receiving 1500 or 2000 mg (n = 56) . Eradication after 2 months was influenced by continuity of drug treatment; 36 of 42 patients with no relapse had received continuous treatment vs six of 14 patients whose drug treatment had been stopped for 7 days or longer . After 2 to 7 months of treatment, acquired resistance associated with relapse was observed . Drug side effects were elevated liver enzyme levels (26%) and impaired hearing (4%) . Concomitant AIDS drugs had no favorable effect on outcome and may have worsened liver toxicity . CONCLUSIONS: Clarithromycin has bacteriologic efficacy against M avium infection in late-stage AIDS, although drug resistance eventually develops . Further studies are needed to investigate safe, effective concomitant drugs. Ned Tijdschr Geneeskd, 1993 Feb 6, 137(6), 291 - 4 {Abdominal typhus and paratyphoid fever in 2 academic hospitals: 1984-1990}; Hustinx WN et al.; A diagnosis of blood culture-positive typhoid (TF; n = 39) or paratyphoid (PTF; n = 17) fever was made in 56 patients admitted to two Dutch university hospitals in the period 1984-1990 . The group of TF patients constituted 9% of the reported national total during those years . A retrospective analysis of available clinical, laboratory and epidemiological data was carried out . Without exception, infections were contracted during travel abroad, especially to India and Indonesia . The clinical features and the response to antimicrobial treatment of TF and PTF proved essentially the same . Fever, headache and anorexia were important symptoms; rose spots and splenomegaly were found in 18/38 and 10/39 with S . typhi respectively . Most patients had a normal white blood cell count; less than half of the patients had thrombocytopenia . A positive Widal-test was found in 15/24 patients with S . typhi . 18/39 patients with S . typhi had been vaccinated; 10 did not know . Amoxycillin was the preferred antimicrobial agent in 69% of cases . Median defervescence time was 5 days in TF and 4 days in PTF . Relapse occurred in 3 TF cases . The recurrence rate after amoxycillin treatment was 7.6% . Profuse intestinal bleeding (1x), septic shock (1x) and cholangitis plus ARDS (1x) were major complications, seen in TF patients only . All patients recovered fully . None of the isolated strains of S . typhi or S . paratyphi proved multiresistant . Surveillance data from the Dutch National Institute of Public Health and Environmental Protection suggest that multidrug-resistance of S . typhi is increasing, especially in strains imported from countries such as India and Pakistan.(ABSTRACT TRUNCATED AT 250 WORDS) N Engl J Med, 1993 Feb 4, 328(5), 308 - 12 Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer; Hentschel E et al.; BACKGROUND . Persistent infection with Helicobacter pylori is associated with the recurrence of duodenal ulcer . Whether the efficacy of bismuth therapy in reducing the rate of recurrence of duodenal ulcer is due to its antimicrobial effects on H . pylori or to a direct protective action on the mucosa is still a matter of debate . METHODS . To study the effect of the eradication of H . pylori on the recurrence of duodenal ulcer, we treated 104 patients with H . pylori infection and recurrent duodenal ulcer with either amoxicillin (750 mg three times daily) plus metronidazole (500 mg three times daily) or identical-appearing placebos, given orally for 12 days . All patients also received ranitidine (300 mg each night) for 6 or 10 weeks . Endoscopy was performed before treatment and periodically during follow-up for up to 12 months after healing . RESULTS . Among the 52 patients given antibiotics, H . pylori was eradicated in 46, as compared with 1 of the 52 given placebo (89 percent vs . 2 percent, P < 0.001) . After six weeks, the ulcers were healed in 48 patients given antibiotics and 39 given placebo (92 percent vs . 75 percent, P = 0.011) . Side effects, mainly diarrhea, occurred in 15 percent of the patients given antibiotics . Among the patients followed up for 12 months, duodenal ulcers recurred in 4 of 50 patients given antibiotics and 42 of 49 given placebo (8 percent vs . 86 percent, P < 0.001) . Ulcers recurred in 1 of 46 patients in whom H . pylori had been eradicated, as compared with 45 of 53 in whom H . pylori persisted (2 percent vs . 85 percent, P < 0.001) . CONCLUSIONS . In patients with recurrent duodenal ulcer, eradication of H . pylori by a regimen that does not have any direct action on the mucosa is followed by a marked reduction in the rate of recurrence, suggesting a causal role for H . pylori in recurrent duodenal ulcer. Quintessence Int, 1993 Feb, 24(2), 141 - 4 The efficacy of Plax prebrushing rinse: a review of the literature; Kozlovsky A et al.; Removal of bacterial plaque is a prerequisite to the prevention and control of periodontal disease . In highly motivated patients, it is possible to control plaque successfully by mechanical means . Because most patients lack sufficient motivation and skill to perform effective plaque control on a regular basis, use of antimicrobial chemical agents is essential to gingival health . In 1985, Plax, a prebrushing oral rinse, was introduced . The manufacturer claims that the solution acts as a detergent that removes some bacterial plaque and loosens the remainder for easy removal by toothbrushing . A review of current dental research related to this claim is presented . The data provided do not support the use of Plax dental rinse as part of an oral hygiene program. J Dermatol, 1993 Feb, 20(2), 88 - 93 A study of the efficacy of antimicrobial detergents for hand washing: using the full-hand touch plates method; Namura S et al.; We studied the effects of four kinds of antimicrobial detergents, 4% chlorhexidine gluconate (CHG), chlorbenzarconium (CBC), 10% povidone-iodine (PVI), 0.3% triclosan (TRI), and one non-medicated detergent (NMD) using the full-hand touch plates method . Before and after 3 minutes of hand scrubbing with a brush, bacterial colonies on the hand surface and subungual bacteria were counted . CHG, CBC, and PVI were excellent antimicrobial detergents against hand surface bacteria, but most of the subungual bacteria remained . The subungual space was the most difficult region from which to eradicate bacteria . TRI was much less effective than hand soap against hand surface bacteria. Pharmazie, 1993 Feb, 48(2), 99 - 106 Reactions of 5-aryl-furan-2,3-diones with acylmethylenetriphenylphosphoranes: synthesis and biological activity of 3(2H)-furanone derivatives; Kozminykh VO et al.; The Wittig reaction of 5-aryl-furan-2,3-diones 1 with acylmethylenetriphenylphosphoranes 2 conducted by heating under reflux in benzene solutions, proceeded regiospecifically to afford 2-acylmethylene-5-aryl-3(2H)-furanones 5 in good yields . When the starting compounds 1 and 2 were allowed to react at room temperature, the stable intermediate 5-aryl-2-hydroxy-2-triphenylphosphoranylidenemethyl-3(2H)-furanone s 15 were yielded . The latter adducts underwent triphenylphosphine oxide elimination on heating to form the same olefins 5 . The structural assignments of the synthesized compounds were made on the basis of their spectral data and X-ray analysis for 5a . Some of the compounds obtained exhibit antimicrobial activity and one compound of the 3(2H)-furanone series exhibited anticonvulsant activity. Kansenshogaku Zasshi, 1993 Feb, 67(2), 154 - 62 Chronic melioidosis: a report of the first case in Japan; Arakawa M et al.; A 41-year-old Japanese male with uncontrolled diabetes mellitus and alcoholic liver dysfunction developed melioidosis after his business trip to Indonesia and Singapore in 1988 . His disease started with spiked fever on the following day after extraction of a tooth, and a liver abscess developed, followed by abscesses in the spleen and in the subphrenic space . In spite of splenectomy and intensive antimicrobial treatments for three months, he developed parotitis, prostatitis, and abscess of the right submandibular gland at 5 to 16-month interval . Pseudomonas pseudomallei was isolated from the blood and pus from each abscess . The lung was not involved . At present, he has returned to work, with continued intravenous instillation of imipenem/cilastatin. Diagn Microbiol Infect Dis, 1993 Feb, 16(2), 135 - 6 In vitro activity of rifaximin, a topical rifamycin derivative, against Chlamydia trachomatis; Prasad ES et al.; Rifaximin is a rifamycin derivative that possesses in vitro activity against a wide range of bacteria . Its antimicrobial spectrum plus poor intestinal absorption have led to consideration of this compound as a topical agent . We evaluated its in vitro activity against clinical and laboratory strains of Chlamydia trachomatis and found that rifaximin exhibits minimum inhibitory concentrations (MICs) at concentrations that would be greatly exceeded in a topical preparation. AIDS, 1993 Feb, 7(2), 223 - 6 Elevated plasma levels of vasoactive intestinal peptide in AIDS patients with refractory idiopathic diarrhoea . Effects of treatment with octreotide; Manfredi R et al.; OBJECTIVE: To evaluate plasma levels of vasoactive intestinal peptide (VIP) in AIDS patients with refractory idiopathic diarrhoea, and to assess the role of treatment with octreotide . PATIENTS: Three AIDS patients were evaluated for severe watery diarrhoea of 2-6 months' duration, which was complicated by weight loss, weakness, and fluid and electrolyte abnormalities . They had not shown a significant response to several regimens of empirical antimicrobial chemotherapy, or symptomatic antidiarrhoeal treatment . METHODS: A complete diagnostic examination, including repeated microbiological evaluation and radiological, ultrasonographic, endoscopic and histological examination, was performed . Plasma levels of VIP were determined by radioimmunoassay and compared with concentrations in a group of healthy subjects . RESULTS: Since no clinically significant results were obtained from standard diagnostic evaluation and empirical therapeutical attempts, idiopathic refractory diarrhoea was diagnosed . Plasma concentrations of VIP were moderately elevated in all three subjects examined, with levels of 11.5, 17.5 and 9.5 pmol/l (values < 8.8 pmol/l in the control group) . One patient received 50-100 micrograms octreotide three times daily subcutaneously for 6 months, resulting in complete resolution of diarrhoea and significant improvement in body weight and quality of life, together with a reduction in VIP concentration to within normal values . CONCLUSIONS: Although the somatostatin analogue octreotide has been used successfully in the management of both infectious and non-infectious AIDS-related diarrhoea, gastrointestinal neuroendocrine function and circulating humoral mediators of diarrhoea have not hitherto been investigated extensively in HIV-infected subjects . Our data on the association of idiopathic secretory diarrhoea and elevated plasma VIP levels provide a possible pathophysiological rationale for identifying AIDS patients whose refractory diarrhoea may be more responsive to octreotide treatment. J Nat Prod, 1993 Feb, 56(2), 245 - 59 Unprecedented oxylipins from the marine green alga Acrosiphonia coalita; Bernart MW et al.; The Oregon marine chlorophyte Acrosiphonia coalita produces an assortment of oxidized polyunsaturated fatty acids, or oxylipins . The smallest of these was a 10-carbon conjugated trienal 1 with antimicrobial properties . Related to 1 were three novel branched-chain conjugated trienals 4, 5, and 9 in which the aldehyde was present as a branch on a 17-carbon fatty acid chain . Additionally, two novel conjugated unbranched trienone octadecanoids 8 and 10 were also isolated and characterized . Finally, a family of related epoxy-alcohols (11, 12, 15, and 17) was obtained from A . coalita . Structures were determined by spectroscopic methods in combination with formation of various degradation products and derivatives . The absolute stereochemistry of several of these metabolites was determined by application of exciton chirality circular dichroic spectroscopy on benzoate derivatives. J Chemother, 1993 Feb, 5(1), 37 - 42 Antimicrobial chemoimmunoprophylaxis in colorectal surgery with cefotetan and thymostimulin: prospective, controlled multicenter study . Italian Study Group on Antimicrobial Prophylaxis in Abdominal Surgery; Periti P et al.; Surgical antimicrobial prophylaxis was performed with a controlled study on 859 evaluable patients randomized into two groups treated with chemoprophylaxis only or chemo- and immunoprophylaxis in colorectal surgery . Immuno and chemoprophylactic treatment (425 patients) consisted of 70 mg i.m . thymostimulin per day for 7 days beginning 48 h before surgery plus 2 g cefotetan at the moment of induction of anesthesia; the other group (434 patients) received only the single dose of antibiotic . Results in the two different groups were significantly different regarding abdominal abscess and the total infectious episodes in the surgical site with lower frequency in patients receiving both thymostimulin and the antibiotic (cefotetan) . Moreover the respiratory tract infections were more than double in those patients not treated with perioperative immunotherapy . Stratifying patients on the basis of grade of skin test reaction, we observed a significantly lower percentage of surgical site infection in hypoergic patients receiving chemo- and immunoprophylaxis. Clin Pharm, 1993 Feb, 12(2), 138 - 49 Sodium imbalance in a patient receiving total parenteral nutrition; Sunyecz L et al.; A case of hyponatremia and then hypernatremia in a hospitalized patient receiving total parenteral nutrition (TPN) is described, and the etiologies, diagnoses, and treatments of hyponatremia and hypernatremia are reviewed . A 23-year-old man whose left leg had been amputated after a motorcycle accident required parenteral nutrition because of an ileus . After developing sepsis, he was given antimicrobials administered in standard dilutions of 5% dextrose injection, contributing 3 L of free water a day to his fluid intake . The patient subsequently became hyponatremic, and the sodium content of the TPN solution was increased to 140 meq/L . Multiple doses of furosemide and albumin were administered because of weight gain and edema of the lower extremity . After 14 days, all antimicrobial therapy was discontinued, and 2 days later the patient became hypernatremic . The sodium content of the TPN solution was decreased and then eliminated . Because of a 16-kg weight loss, diuretic therapy was stopped . This patient's hyponatremia was caused by administration of large amounts of sodium-free fluids (i.e., antimicrobials in 5% dextrose injection) . The most appropriate management would have been to change the fluids in which the antimicrobials were diluted, with no change in the sodium content of the TPN solution . The patient's subsequent hypernatremia is best explained by a loss of free water . To manage this condition, it would have been appropriate to administer 5% dextrose injection to replace the free-water loss . Once the patient had reached baseline weight and therapy with the diuretic had been discontinued, maintenance therapy with 0.45% sodium chloride injection would have been beneficial . No change in the TPN sodium content should have been required . It is important to recognize all factors that predispose patients receiving TPN to hyponatremia and hypernatremia . Although the focus is often on the sodium content of the TPN solution, sodium and fluid can be administered by other means, including medication admixtures and maintenance intravenous fluids. An Med Interna, 1993 Feb, 10(2), 91 - 7 {Helicobacter pylori and the treatment of gastric ulcer . Reflections and uncertainties}; Dobrilla G et al.; The authors examine the relationship between Helicobacter pylori and gastric ulcer therapy, analyzing both the data suggesting that eradication of the organism renders the gastric mucosa less susceptible to development of gastric ulcer and the substantial body of evidence to the contrary . They review the results reported in clinical trials with colloidal bismuth subcitrate, antimicrobial agents (furazolidone), and combinations of antiulcer and antimicrobial agents (H2-antagonist + cefixime, H2-antagonist + metronidazole) . Also analyzed is the relationship between Helicobacter pylori eradication and ulcer recurrence; only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing . The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of Helicobacter pylori facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy. Curr Opin Immunol, 1993 Feb, 5(1), 97 - 102 Antibiotic peptides and serine protease homologs in human polymorphonuclear leukocytes: defensins and azurocidin; Gabay JE et al.; The azurophil granule, a specialized lysosome of neutrophils, contains two families of antimicrobial proteins, each with four members . They are the defensins, comprising human neutrophil protein 1, -2, -3 and -4, on the one hand and the serprocidins, comprising cathepsin G, elastase, proteinase 3 and azurocidin, on the other . Defensins appear to contribute to mammalian as well as invertebrate immunity . Recent studies show that defensins and structurally related peptides are found not only in phagocytes but also in intestinal and respiratory cells . Aside from their antibiotic function, members of the defensin family may also act as hormonal agents . Within the serprocidin family the genes encoding the novel antibiotics and serine protease homologs azurocidin and proteinase 3 have been identified recently. Curr Opin Immunol, 1993 Feb, 5(1), 74 - 82 The limulus clotting reaction; Iwanaga S; Our biochemical studies on the hemolymph coagulation-complement system using limulus indicate that the circulating hemocytes contain at least four serine protease zymogens and one clottable protein, coagulogen, which constitute a cascade triggered by bacterial endotoxins and (1,3)-beta-D-glucan . We also found several antimicrobial substances, tachyplesin peptides and anti-lipopolysaccharide factor, in the hemocytes . These clotting factors and antimicrobial substances are released into the hemolymph in response to lipopolysaccharide, where they cooperate in immobilization and killing of invading microorganisms as a host defense. Antimicrob Agents Chemother, 1993 Feb, 37(2), 317 - 21 Susceptibilities of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum strains to antimicrobial agents in vitro; ter Laak EA et al.; The purpose of this study was to determine the susceptibility of various strains of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum, which are prevalent causes of pneumonia in calves, to 16 antimicrobial agents in vitro . The MICs of the antimicrobial agents were determined by a serial broth dilution method for 16 field strains and the type strain of M . bovis, for 19 field strains and the type strain of M . dispar, and for 17 field strains of U . diversum . Final MICs for M . bovis and M . dispar were read after 7 days and final MICs for U . diversum after 1 to 2 days . All strains tested were susceptible to tylosin, kitasamycin, and tiamulin but were resistant to nifuroquine and streptomycin . Most strains of U . diversum were intermediately susceptible to oxytetracycline but fully susceptible to chlortetracycline; most strains of M . bovis and M . dispar, however, were resistant to both agents . Strains of M . dispar and U . diversum were susceptible to doxycycline and minocycline, but strains of M . bovis were only intermediately susceptible . Susceptibility or resistance to chloramphenicol, spiramycin, spectinomycin, lincomycin, or enrofloxacin depended on the species but was not equal for the three species . The type strains of M . bovis and M . dispar were more susceptible to various antimicrobial agents, including tetracyclines, than the field strains . This finding might indicate that M . bovis and M . dispar strains are becoming resistant to these agents . Antimicrobial agents that are effective in vitro against all three mycoplasma species can be considered for treating mycoplasma infections in pneumonic calves . Therefore, tylosin, kitasamycin, and tiamulin may be preferred over oxytetracycline and chlortetracycline. Antimicrob Agents Chemother, 1993 Feb, 37(2), 183 - 6 In vitro and in vivo activities of the nitroimidazole CGI 17341 against Mycobacterium tuberculosis; Ashtekar DR et al.; CGI 17341 (2-ethyl-5-nitro-2,3-dihydro{2-1b}imidazo-oxazole) is a novel orally active representative of the 5-nitroimidazole series of antimicrobial agents . At concentrations ranging from 0.1 to 0.3 micrograms/ml, CGI 17341 inhibited the drug-susceptible and multi-drug-resistant strains of Mycobacterium tuberculosis . CGI 17341 had no cross-resistance with isoniazid, rifampin, streptomycin, or ethambutol . While the in vitro activity of CGI 17341 against M . tuberculosis was comparable to those of isoniazid and rifampin, it was superior to those of streptomycin, ciprofloxacin or norfloxacin, and oxazolidinone DuP 721 . The MIC of CGI 17341 was not affected when the pH of the medium was decreased from 6.8 to 5.6, while four- to sixfold increases in the MICs of ciprofloxacin and isoniazid were observed . In mice infected with M . tuberculosis, the 50% effective dose for CGI 17341 was 7.7 mg/kg of body weight (95% confidence limits, 3.5 and 10.27) when administered on days 11 and 12 postinfection . CGI 17341 gave a dose-dependent (r = 0.995) and significant increase in the survival time . Our data indicate that the 5-nitroimidazole CGI 17341 is a promising and novel antituberculosis compound with potent in vitro and in vivo activities . Further investigations on this compound are warranted. Anal Biochem, 1993 Feb 1, 208(2), 382 - 6 Purification of cysteine-rich bioactive peptides from leukocytes by continuous acid-urea-polyacrylamide gel electrophoresis; Harwig SS et al.; A new continuous acid-urea-polyacrylamide gel electrophoresis (CAU-PAGE) preparative method was developed and used to purify rabbit and human defensins . With it, we identified two post-translationally modified forms of rabbit defensins NP-1 and NP-2, and purified a processed RANTES (beta-intercrine) peptide from leukophoresed human leukocytes . CAU-PAGE afforded approximately 70% recovery of rabbit defensin NP-5 . The recovered defensins were not N-terminally modified, and their in vitro antimicrobial activity was equivalent to that of defensins purified by previously described chromatographic methods . Since CAU-PAGE is performed under nonreducing conditions, it should be especially useful for purifying cationic peptides with intramolecular disulfide bonds, such as defensins and alpha or beta-intercrines. Hematol Oncol Clin North Am, 1993 Feb, 7(1), 255 - 74 Growth factors in the management of adult acute leukemia; Bernstein SH; This review has explored the various ways that growth factors may be used in the management of adult acute leukemia . Growth factors have the potential to reduce the morbidity and mortality of both induction and postremission therapy by enhancing hematopoietic recovery or, when used as an adjunct to standard antimicrobial therapy, reducing the infectious complications of chemotherapy . In addition, they may have favorable effects on the biology of leukemia either by recruitment of leukemic progenitors into cycle, rendering them more sensitive to the cytotoxic effects of chemotherapy, or by inducing the terminal differentiation of the leukemic clone . Finally, disruption of aberrant growth factor networks, thought to play a role in the pathogenesis of leukemia, may be a therapeutic strategy now that soluble receptors and receptor antagonists to such growth factors as IL-1 are available . Whether growth factors used in such ways will have beneficial, or in fact adverse, effects on the treatment outcome for acute leukemia is not yet known . As such, the use of growth factors in the management of adults with acute leukemia is still experimental and needs to be studied in the context of clinical trials . Perhaps the ultimate benefit to be derived from the study of these growth factors will be a deeper understanding of the genetic perturbations that define the leukemic state . The development of molecular therapeutic techniques, such as gene transfer technology and the use of antisense oligonucleotides, has paralleled our increasing knowledge of cytokines . The hope is that as we come to understand leukemia at the molecular level, we will be able to develop the new therapeutic tools necessary to increase the numbers of patients cured. J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 49 - 63 Antimicrobial prophylaxis in neurosurgery; Brown EM; Attempts to reach conclusions concerning the efficacy of antimicrobial prophylaxis in neurosurgery have been frustrated by the paucity of clinical trials which cannot be invalidated by flaws in their design and/or execution . Although the data are inconclusive, the weight of evidence suggests that antibiotics probably exert a protective effect in clean, non-implant procedures, for which a first or second generation cephalosporin would be appropriate . No consensus has been reached regarding the benefits of prophylaxis to patients undergoing the implantation of a CSF shunt and surgeons will therefore need to come to a decision based on their own experiences; those who elect to give antibiotics will still be left with the problems of choosing the optimum regimen and route of administration . Nor can valid conclusions be drawn about the efficacy of prophylaxis in patients with dural fistulae; a rational and ethically supportable approach would be to withhold antibiotics and to monitor patients closely for the early signs of meningitis, instituting appropriate empirical therapy should this complication arise. J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 35 - 41 Antimicrobial prophylaxis in 'clean' surgery: hernia repair; Ranaboldo CJ et al.; Antimicrobial prophylaxis is not traditionally employed for patients undergoing 'clean' surgery . The true rates of septic complications are grossly under reported for this group of patients, with up to 72% of all complications occurring, undetected by the surgical team, after discharge from hospital . The implied costs of these infections, coupled with the costs to both the patient and the community services, suggest that antimicrobial prophylaxis should be seriously considered for many types of 'clean' surgery . This can now be made both more straightforward and cost-effective by employing the oral route of administration. J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 107 - 18 Pharmacoeconomics of antimicrobial prophylaxis; Davey PG et al.; Pharmacoeconomic analysis of the prevention of infection is based on quantification of the benefits which result from prevention, rather than simple counting of the number of cases prevented . In general, benefits are best quantified as continuous variables which measure severity as well as occurrence, for example, cost of antibiotics prescribed is a useful continuous measure of severity to add to a discontinuous measure, such as number of patients who received antibiotics . Considerable progress has been made in the USA with the application of decision analysis to clarify the options available for dealing with a problem, the probability of good and bad outcomes for each choice and the utility which is associated with each outcome . These techniques deserve wide application . Much existing practice is based on limited, poor quality information about the occurrence and severity of infection . This situation can only be improved by wider application of standardized methods for definition of occurrence of infection and of underlying risk of infection. J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 101 - 5 Antimicrobial prophylaxis during biliary endoscopic procedures; Alveyn CG; Endoscopic retrograde cholangiopancreatography (ERCP) is a well-established technique and has considerable diagnostic value and therapeutic potential in patients with hepatobiliary disease . In experienced hands, ERCP is a safe procedure . The most important complications are pancreatitis, infection--ascending cholangitis and septicaemia--instrumental injury and haemorrhage . The reported incidence of bacteraemia complicating ERCP varies considerably (0.16-16%) but this may be due to differences in specimen collection and culture techniques . Clinically significant sepsis is the commonest cause of death due to ERCP with a case fatality rate of 8-20% . As the danger of sepsis was increasingly recognized, antibiotic prophylaxis was considered as routine policy in many centres; supporting evidence was retrospective . Significant differences between antibiotic and control groups are difficult to confirm in clinically controlled trials because of an insufficient number of patients and the low incidence of cholangitis and septicaemia . The optimum regimen is unknown and there is uncertainty regarding the duration of treatment required to provide adequate protection . Local variations in bacterial sensitivity should be taken into account when choosing the antimicrobial agent . In patients without clinical signs of biliary obstruction the risk of infection is low and prophylaxis may be unnecessary. J Antimicrob Chemother, 1993 Feb, 31 Suppl B, 1 - 9 Antimicrobial prophylaxis in surgery: microbiological factors; Sanderson PJ; Various aspects of prophylaxis in surgery are discussed . The timing of antibiotic doses is analysed in relation to the Burke laboratory model and the lag-phase of bacterial growth . Areas where further data is required: the effect of locally applied antibiotics, protection against sources of organisms and new approaches to prophylaxis are discussed . The ecological effects of antibiotics are described in relation to prophylaxis. Br J Surg, 1993 Feb, 80(2), 148 - 54 Pancreatic infection complicating acute pancreatitis; Widdison AL et al.; Pancreatic infection is the leading cause of death from acute pancreatitis . Patients with severe necrotizing pancreatitis are most at risk . Early computed tomography and percutaneous fine-needle aspiration microbiology of areas of pancreatic necrosis enable early diagnosis . Pancreatic infection should be treated surgically, although sterile necrosis may be managed conservatively . The role of antimicrobial drugs is uncertain. Clin Infect Dis, 1993 Feb, 16(2), 301 - 2 Oral candidiasis is associated with low levels of parotid calprotectin in individuals with infection due to human immunodeficiency virus; Muller F et al.; The level of the antifungal leukocyte protein calprotectin was determined in parotid saliva from 44 individuals with infection due to human immunodeficiency virus (HIV) and 19 healthy HIV-seronegative controls . Nine of the HIV-infected subjects suffered from oral candidiasis . Similar calprotectin levels were found in subjects with HIV infection as a whole group and in controls . When HIV-infected individuals with or without oral candidiasis were compared, the calprotectin level was significantly lower in the former group (67 micrograms/L vs . 216 micrograms/L) . We suggest that calprotectin may play a role in the defense against oral candidal infections in HIV-infected patients, although several other antimicrobial factors also are probably operative. Clin Infect Dis, 1993 Feb, 16(2), 276 - 85 Pertussis in Missouri: evaluation of nasopharyngeal culture, direct fluorescent antibody testing, and clinical case definitions in the diagnosis of pertussis; Strebel PM et al.; No diagnostic test for pertussis in routine use in the United States has both high sensitivity and high specificity . During a statewide increase in the incidence of pertussis in Missouri, we studied the clinical features of 153 patients with suspected pertussis in the Greater St . Louis area from whom a specimen for pertussis culture had been taken between 15 May and 19 September 1989 . In this cross-sectional study, nasopharyngeal cultures were more likely to be positive for persons whose specimens were collected < 21 days after cough onset (adjusted rate ratio {RRa} and 95% confidence interval = 3.4; 1.5-8.0) and who were not receiving erythromycin/sulfamethoxazole prior to the culture {RRa = 5.8; 0.8-40.6}, who had received fewer than three prior doses of pertussis vaccine {RRa = 1.8; 0.8-4.2}, and whose specimen was in transit to the laboratory for < 4 days {RRa = 2.0; 0.8-5.5} . Among children < 5 years of age, spasmodic cough plus a lymphocytosis of > 10,000/mm3 was the acute symptom complex associated with the highest predictive value for a positive culture result (67%) . Cough for > or = 14 days plus whoop was sensitive (81%) and specific (58%) for identifying children with culture-confirmed pertussis . Direct fluorescent antibody staining performed well as a screening test for pertussis but requires substantial commitment of personnel and resources . In the absence of a positive culture result, clinical case definitions should be used for decision making (e.g., initiation of antimicrobial therapy and routine case reporting). Bol Med Hosp Infant Mex, 1993 Feb, 50(2), 79 - 87 {The use of antibiotics in a community of Mexico City . I . A household survey}; Bojalil R et al.; Based on previous community-oriented studies an irrational use of antibiotics, particularly in developing countries, has been suggested . In order to describe the pattern of antibiotic use in a periurban community in Mexico City, 1659 randomly selected households were visited and an interview to the housewife was carried out . Of 8279 individuals 425 (5%) had used at least one antimicrobial in the preceding two weeks . Main perceived reasons for drug use were: respiratory tract ailments (58%) and acute diarrhea (25%) . Antibiotic therapy was given in 27% of respiratory diseases and in 37% of all diarrheal episodes . Most commonly used drugs were: penicillins (43%), erythromycin (13%), metronidazole (9%), neomycin (6%), cotrimoxazole (6%) and tetracyclines (6%) . While self-medication was common (19%) the majority of antibiotics were prescribed by a physician (81%) . Approximately two thirds of individuals using an antibiotic did it for less than five days . Our data suggest a frequent misuse of antibiotics and support the future assessment, in this community, of physician prescribing practices, the determinants of self-medication as well as the impact of this drug use on the selection of resistant bacterial strains. Ann Pharmacother, 1993 Feb, 27(2), 178 - 9 Retroperitoneal abscess caused by Mycobacterium chelonae and treatment; Idemyor V et al.; OBJECTIVE: To report a case of retroperitoneal abscess caused by Mycobacterium chelonae and treatment . DESIGN: Case report . SETTING: Private community teaching hospital . PATIENTS: A patient was admitted to the hospital following a gunshot to the flank . The bullet passed through the iliac crest and lodged in the abdomen . INTERVENTION: The patient was treated with cefazolin, trimethoprim/sulfamethoxazole, and amikacin at different times . OUTCOME: The patient responded well to pharmacologic treatment and at 18-month follow-up, he is disease free . CONCLUSIONS: Antimicrobial agents with in vitro activity against M . chelonae, especially amikacin-containing regimens, are recommended for treating M . chelonae infection. Ophthalmology, 1993 Feb, 100(2), 187 - 91 Corneal complications associated with the use of crack cocaine; Sachs R et al.; BACKGROUND: A case series of patients with corneal complications associated with crack cocaine use is presented . Patients had infectious keratitis or sterile epithelial defects . METHODS: Entry criteria into this series included the presence of an infectious corneal ulcer or sterile epithelial defect after the patient used crack cocaine routinely . Patients were prospectively identified from July 1, 1989 to June 30, 1991 . RESULTS: Fourteen patients with crack-related corneal problems were identified . In 10 patients with infectious corneal ulcers, both bacterial and fungal organisms were isolated, and patients were treated with appropriate antimicrobial therapy . The group of patients with sterile corneal epithelial defects were seen after they had rubbed their eyes vigorously after crack cocaine use . The epithelial defects were treated and healed without complication . CONCLUSION: Crack cocaine users appear to represent a unique subset of young patients predisposed to infectious keratitis and corneal epithelial defects . A number of hypotheses are offered to explain this effect . Both ophthalmologists and the general public should be aware of these severe corneal problems associated with the use of crack cocaine. J Clin Periodontol, 1993 Feb, 20(2), 96 - 104 Metronidazole in periodontitis (IV) . The effect of patient compliance on treatment parameters; Loesche WJ et al.; Patient compliance with the unsupervised usage of prescription medication can be poor . In the treatment of periodontal infections with systemic antimicrobial agents, in situations where the efficacy of the antimicrobial agent is being evaluated, non-compliance could underestimate the true efficacy of the agent . Metronidazole is an agent with reported success in the treatment of anaerobic periodontal infections . Metronidazole is particularly effective in vitro against spirochetes, and this efficacy was investigated as a means of measuring patient compliance with metronidazole usage . Patients who had high proportions of spirochetes, i.e., > 20%, in plaques removed from diseased periodontal sites, were given metronidazole (500 mg bid) under supervision . In all individuals who received the metronidazole, there was a significant and rapid decline and/or disappearance of spirochetes from the plaque during the time interval that metronidazole was detectable in the saliva . This observed decline in spirochetes was then used to determine which patients had been compliant in a double-blind clinical trial involving the unsupervised usage of metronidazole . Only 10 of 18 patients (56%) were considered compliant in their usage of metronidazole . These 10 patients experienced a significantly greater benefit from the metronidazole than did the 8 patients who were considered noncompliant, i.e., a reduction of surgical needs of 8.3 teeth per compliant patient versus 3.6 teeth per non-compliant patient . A test for the hydrolysis of the synthetic peptide (BANA) was also able to identify most non-compliant patients . Clinical trials involving the unsupervised usage of systemic medication need to take into account patient non-compliance. Eur J Surg Oncol, 1993 Feb, 19(1), 10 - 6 Wound dressing in major head and neck cancer surgery: a prospective randomized study of gauze dressing vs sterile vaseline ointment; Phan M et al.; A total of 207 patients were randomized in a prospective comparative study of standard gauze dressing vs sterile vaseline ointment . 179 patients were evaluable . All patients received antimicrobial prophylaxis . The two groups (86 standard and 93 vaseline) were comparable as far as age (mean, 57 yr; range, 21-84), genders (155 males/24 females), weight (mean, 66 kg; range, 40-69), type of surgery, previous or concomitant anticancer treatment . Severity of surgery was identical, as was the severity of cancer, in the two groups . Wound infection within 20 days of surgery occurred in 31.2% (29/93) of the vaseline group and 24.4% (21/86) in the standard group (NSS) . Bacteremia occurred in three patients from the vaseline group and in four patients from the standard group . Bronchopneumonia occurred in 10 patients from the vaseline group and 14 patients in the standard group . The spectrum of microorganisms recovered was similar in the two groups . The need for antimicrobial treatment (empiric or for documented infections) within 20 days after surgery was 34.4% (32/93) in the vaseline group and 36.0% (31/86) in the standard group . The median delay to infection (range in days) in the vaseline group was 9 (5-15) for wound and 6 (1-12) for bronchopneumonia . For the standard group the corresponding delays were 8 (4-15) and 7 (2-19) . Vaseline dressing was not associated with an increased risk of infection as compared to the standard gauze dressing. J Periodontol, 1993 Feb, 64(2), 137 - 41 Retention of antimicrobial activity by human root surfaces after in situ subgingival irrigation with tetracycline HCl or chlorhexidine; Stabholz A et al.; Substantivity of tetracycline HCl and chlorhexidine digluconate was assessed in extracted teeth . Fifty periodontally compromised teeth scheduled for extraction with probing depths ranging between 6 and 12 mm were root planed and then irrigated in situ with 1 of 4 solutions: tetracycline HCl at concentrations of 10 or 50 mg/ml, 0.12% chlorhexidine digluconate, or 0.9% sterile saline . Each tooth was exposed to 150 ml of the respective irrigation solution . Following extractions, the teeth were transferred to tris buffered saline and incubated at room temperature for 22 days . Incubation solutions were replaced at 24-hour intervals . Removed solutions were examined for desorbed antimicrobial activity using a microtiter assay in which bacterial growth was evaluated by optical density readings . Tetracycline HCl 50 mg/ml exhibited significantly greater antimicrobial activity than chlorhexidine digluconate for 12 days and greater than saline for 16 days . Tetracycline HCl 10 mg/ml exhibited significantly greater antimicrobial activity than chlorhexidine digluconate and saline for 4 days . Chlorhexidine digluconate did not exhibit any significant antimicrobial activity at any time point . Our findings demonstrate long-lasting substantivity of tetracycline HCl, but not chlorhexidine digluconate, by teeth exposed to a single episode of pocket irrigation of their periodontally-exposed roots . The amount of antimicrobial activity retained is proportional to the concentration of tetracycline HCl used for irrigation. J Intern Med, 1993 Feb, 233(2), 107 - 10 Opportunistic infections of the oesophagus in AIDS patients: clinical and therapeutic problems; Bianchi Porro G et al.; The gastrointestinal tract is frequently involved in the acquired immunodeficiency syndrome . One of the most common digestive manifestations is dysphagia/odynophagia which constitutes the presenting feature of the syndrome in a number of patients and occurs in many others during the subsequent phases of the illness . In the majority of cases it is due to an oesophageal infection by opportunistic pathogens (fungi or viruses or both) and may be successfully treated, at least temporarily, by specific antimicrobials . The present article examines the most recent acquisitions in terms of diagnosis and treatment of such common clinical problem. J Clin Microbiol, 1993 Feb, 31(2), 351 - 3 Colonization by enteroaggregative Escherichia coli in travelers with and without diarrhea; Cohen MB et al.; Enteroaggregative Escherichia coli (EAggEC) has been found to be associated with pediatric diarrhea in developing countries . In order to determine the role of EAggEC as an agent of traveler's diarrhea, we used a sensitive and specific DNA probe for EAggEC to screen bacterial colony blots from 278 volunteers before and after travel . Colonization with EAggEC was infrequent (2.5%) prior to travel but rose to 27 to 33% after travel in volunteers who took either placebo or trimethoprim-sulfamethoxazole . Travelers who took trimethoprimsulfamethoxazole were colonized with organisms that were uniformly resistant to that antimicrobial agent; when volunteers received ciprofloxacin, colonization with EAggEC was prevented (2.0%) . Although colonization rates were high in the placebo and trimethoprim-sulfamethoxazole groups, only a minority of travelers who were colonized with EAggEC experienced diarrhea . On the basis of our data, we suggest that colonization with EAggEC alone is not sufficient to cause traveler's diarrhea. Epidemiol Infect, 1993 Feb, 110(1), 63 - 70 Epidemiology of typhoid fever in Singapore; Yew FS et al.; A total of 1452 cases of typhoid fever was notified in Singapore from 1980-9 . The morbidity rates of indigenous cases showed a steady decline from 5.9 per 100,000 population in 1980 to 1.2 per 100,000 population in 1989 . The mean case fatality was 0.8% . Children, adolescents and young adults were most susceptible to typhoid fever . There was no significant difference in morbidity rates between the major ethnic groups . The vast majority of indigenous cases were sporadic while outbreaks accounted for almost one third of them . Food was the main vehicle of transmission . The commonest indigenous phage types were B1, D1 and A . Antimicrobial resistance was infrequently seen . The proportion of imported cases rose from 32% in 1980 to 72% in 1989 . Almost half (48.5%) of all imported cases were local residents who contracted typhoid fever while travelling in endemic countries . As imported cases assume greater importance in the epidemiology of typhoid fever in Singapore, further drop in typhoid fever incidence would require reduction of travel-related cases through greater awareness of food hygiene and effective vaccination. Hepatology, 1993 Feb, 17(2), 196 - 201 Prospective controlled trial of selective parenteral and enteral antimicrobial regimen in fulminant liver failure; Rolando N et al.; To compare the efficacy of a selective parenteral and enteral antimicrobial regimen in patients with fulminant liver failure, we classified 104 patients on reaching grade II encephalopathy as infected or non-infected . Patients who were infected were randomly assigned to receive IV cefuroxime (group 1) or selective parenteral and enteral antimicrobial regimen (group 2) . Noninfected patients were randomly selected to receive either selective parenteral and enteral antimicrobial regimen (group 3) or no initial antimicrobials until clinically indicated (group 4) . The four groups were comparable regarding age, sex, cause of disease, coma grade, international normalization ratio, presence of kidney failure and indicators of poor prognosis on admission to the study . Clinical parameters such as white cell count, temperature or changes in the chest radiograph, which were used to stratify patients into those infected or not, were not good predictors of infection because early infection rates were similar in the two groups . Three patients died within 24 hr and were excluded from the analysis . We found 42 microbiologically confirmed infections: group 1, 6 of 21; group 2, 8 of 21; group 3, 9 of 28; and group 4, 19 of 31 . A reduction in infection was seen between groups 3 and 4 (p < 0.05) . Patients receiving the selective parenteral and enteral antimicrobial regimen (groups 2 and 3) had fewer infections than the control group (group 4) (p < 0.005) . Groups receiving early antimicrobial therapy (groups 1, 2 and 3) had a lower incidence of infection compared with group 4 (p < 0.0005) . Overall, 55.5% survived, with no significant difference between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS) Gynecol Oncol, 1993 Feb, 48(2), 227 - 31 Feasibility of intraoperative administration of chemotherapy for gynecologic malignancies: assessment of acute postoperative morbidity; Segna RA et al.; In order to assess the acute effects of the intraoperative administration of intraperitoneal (IP) carboplatin with and without intravenous (IV) doxorubicin in patients with gynecologic malignancies, 25 patients were treated at the conclusion of their surgical procedure . Twenty-three had epithelial ovarian cancer and 2 had advanced endometrial cancer . Twelve patients received IP carboplatin and IV doxorubicin at the conclusion of their primary cytoreduction . The remaining 13 received IP carboplatin alone and consisted of 4 reassessment laparotomies for ovarian cancer, 7 secondary cytoreductions, 1 minilaparotomy for the placement of an IP catheter, and 1 second-look laparoscopy . The median age of the 25 patients was 59 years . Eight patients underwent bowel resections with anastomoses; 2 had ureteral resections and ureteroneocystostomies, 1 required a splenectomy, and 1 underwent a partial hepatic resection . There were no mortalities . Three of the 13 patients who received the IP carboplatin alone had postoperative fevers with no infectious source, which did not delay discharge . No other morbidity was noted in this group . However, 7 patients who received IV doxorubicin along with the IP carboplatin developed severe leukopenia requiring antimicrobial and colony-stimulating factor support . One patient required reexploration for postoperative hemorrhage and also developed a pulmonary embolus . One woman developed postoperative pneumonia . The median hospital stay for the 25 patients was 9 days . Intraoperative chemotherapy can be administered with tolerable immediate adverse effects. J Dent Res, 1993 Feb, 72(2), 517 - 23 In vitro antimicrobial activity of the human neutrophil cytosolic S-100 protein complex, calprotectin, against Capnocytophaga sputigena; Miyasaki KT et al.; Calprotectin is a complex of two anionic proteins found in abundance in the cytosol of neutrophils, certain macrophages, and oral epithelial keratinocytes . Bacteria of the genus Capnocytophaga are pathogens of periodontal origin which can cause systemic infection in neutropenic subjects . Recently, it has been observed that Capnocytophaga may be internalized by neutrophils within the cytosol rather than within a membrane-delimited phagosome . The purpose of this study was to test the in vitro antibacterial effect of the cytosolic complex, calprotectin, against Capnocytophaga sputigena . Calprotectin was purified from the cytosol of human neutrophils by gel filtration and anion exchange FPLC, and it exerted potent in vitro antimicrobial effects against C . sputigena . Net bacteriostatic activity was exerted up to 18 h, after which bactericidal effects were observed . Both net bacteriostatic and bactericidal activity occurred at concentrations above 20 micrograms/mL and exhibited identical dose-response characteristics . Particle counts increased in the presence of calprotectin, despite net bacteriostasis as assessed by changes in colony-forming units (CFU) . Dose-response characteristics and direct particle counts suggested that net bacteriostatic effects were the result of balanced cell division and death, rather than suspension of cell division . We conclude that calprotectin can be a significant contributor to host defense against infection by Capnocytophaga. Eur J Clin Microbiol Infect Dis, 1993 Feb, 12(2), 131 - 3 Effect of pH variation on the susceptibility of Helicobacter pylori to three macrolide antimicrobial agents and temafloxacin; Malanoski GJ et al.; The in vitro susceptibility of 27 clinical isolates of Helicobacter pylori to erythromycin, clarithromycin, azithromycin and temafloxacin under various pH conditions was evaluated . Clarithromycin (MIC90 0.03 micrograms/ml) was found to be significantly more active than either erythromycin (MIC90 0.125 micrograms/ml) or azithromycin (MIC90 0.25 micrograms/ml) at a neutral pH . Lowering the pH to 5.75 resulted in a loss in efficacy from 8- to 32-fold for all three macrolides studied . The MIC90 of clarithromycin (0.5 micrograms/ml) remained lower than those of azithromycin (2 micrograms/ml) and erythromycin (4 micrograms/ml) . No synergism or antagonism was observed with combinations of clarithromycin and temafloxacin at either the neutral or lower pH values. Farmaco, 1993 Feb, 48(2), 159 - 89 Synthesis and antimicrobial activity of DNA-gyrase inhibiting derivatives of 4-oxo-1,4-dihydro-3-pyridinecarboxylic acid; Bassini C et al.; A series of 6-substituted-1-aryl-4-oxo-1,4-dihydronicotinic acids were synthesised as monocyclic analogues of the quinolones . The 6-(2-aryl-1-methylethenyl)- and of the 6-(2-arylethenyl)-substituted compounds were shown to possess antibacterial properties that correlate with DNA gyrase inhibitory activity . Differently from the quinolones the antimicrobial activity of the compounds of this study is predominantly against Gram positive strains . The structure-activity relationships ascertained for these monocyclic compounds differ from those established for the quinolones. Int J Immunopharmacol, 1993 Feb, 15(2), 99 - 111 Effects of clofazimine analogues and tumor necrosis factor-alpha individually and in combination on human polymorphonuclear leukocyte functions in vitro; Krajewska MM et al.; In the present study the individual and interactive effects of clofazimine, or three analogues of this agent (selected on the basis of similar or superior pro-oxidative properties: B669, B746 and B4021) and human recombinant TNF-alpha on the generation of antimicrobial oxidants by human polymorphonuclear leukocytes (PMNL), as well as release of granule enzymes from these cells, were investigated in vitro . All four riminophenazines at the concentrations tested (0.5 and 1.0 micrograms/ml) significantly increased myeloperoxidase (MPO)-mediated iodination, superoxide (0(2).-) generation, oxygen (0(2)) consumption and chemiluminescence (CL), as well as the release of both primary and secondary granule contents (measured as the release of MPO, lysozyme and vitamin B12-binding protein) by stimulated PMNL . Similar, but less impressive effects were observed with TNF-alpha (0.4-50.0 ng/ml) . When PMNL were preincubated with both TNF-alpha and clofazimine or its analogues, the observed stimulation of cellular oxidative metabolism and granule enzyme release was at least additive in many assays . These data demonstrate that the spectrum of effects of clofazimine and its analogues on PMNL closely resemble those of TNF-alpha . Furthermore, TNF-alpha potentiates the pro-oxidative effects of clofazimine and its analogues on PMNL . Among the riminophenazines tested, clofazimine and B669 appear to be the most potent pro-oxidative agents for PMNL. Nippon Geka Gakkai Zasshi, 1993 Feb, 94(2), 159 - 64 {Evaluation of antimicrobial system of polymorphonuclear leukocytes and opsonic activity in patients with congenital biliary atresia}; Kuroiwa M et al.; Postoperative ascending cholangitis (AC) is a serious problem in patients with biliary atresia (BA) . It was reported that this complication was due to impaired functions of polymorphonuclear leukocytes (PMNs) . We investigated the oxygen-dependent bactericidal activities including the ability to generate O2-, Myeloperoxidase (MPO) activity and opsonic activity using chemiluminescence method . The serum complement level and fibronectin level were also examined . O2- generating ability was 30.7 +/- 4.5 x 10(4) counts/min (cpm) in BA and 37.4 +/- 4.4 x 10(4) cpm in controls (p < 0.01) . There was a significant difference in serum C4 between these two groups . No difference was found in opsonic activity, MPO activity, C3A, C3 and fibronectin . The O2- generating ability of the PMNs in BA was decreased but the opsonic and MPO activity were not depressed . From these results it is suggested that the frequent occurrence of AC in BA is not caused by low opsonic activity but may be associated with decreased O2- generation . Because of low C4 concentration, activation of classical pathway may also be impaired in BA. Antimicrob Agents Chemother, 1993 Feb, 37(2), 287 - 92 Effects of new quinolones on Mycoplasma pneumoniae-infected hamsters; Arai S et al.; The efficacies of the new quinolones temafloxacin, ofloxacin, and ciprofloxacin were investigated against Mycoplasma pneumoniae in an experimental hamster pneumonia model . Hamsters were infected intratracheally with M . pneumoniae and sacrificed 18 h after the final medication, and their lungs were aseptically removed, homogenized, and cultured quantitatively . The efficacies of these drugs were determined by the CFU of M . pneumoniae in lungs . Temafloxacin and ofloxacin, but not ciprofloxacin, were active when the oral administration of 200 mg/kg of body weight per day (once per day) for 5 days was initiated 24 h after infection . Although no effect on the elimination of M . pneumoniae was observed after the administration of these drugs at 200 mg/kg/day at 5 days after infection, the continuous administration for 15 days of temafloxacin, but not ofloxacin or ciprofloxacin, significantly reduced viable M . pneumoniae in the lungs . These results suggest that temafloxacin and ofloxacin are effective in the acute phase of infection and, moreover, that temafloxacin is effective in the late stage of infection during which progressive lung alterations and continuous increases in mycoplasmal growth occurred . The peak levels of temafloxacin in sera and lungs after oral administration were similar to those of ofloxacin and higher than those of ciprofloxacin . The areas under the curve of temafloxacin in the lung tissue, however, were higher than those of ofloxacin and ciprofloxacin . On the basis of these results, temafloxacin and ofloxacin might be promising antimicrobial agents for the treatment of mycoplasmal infection. Zentralbl Veterinarmed A, 1993 Feb, 40(1), 73 - 9 Pharmacokinetics of the gyrase inhibitor marbofloxacin: influence of pregnancy and lactation in sows; Petracca K et al.; Six pregnant sows were treated in early pregnancy, late pregnancy and during lactation . Marbofloxacin was administered (2 mg/kg body weight) intravenously and orally . The active drug concentration in the plasma was quantitated by use of high performance liquid chromatography (HPLC) . Pharmacokinetic parameters were calculated by use of statistical moments . In lactating animals, the concentrations in milk were also determined by HPLC . Mean elimination half-life of the drug after oral administration was significantly shorter in lactating sows (5.74h) than that of the early pregnancy group (10.09h) . Total body clearance was highest in the lactating sows (3.27 ml/minute.kg body weight) . The volume of distribution was large in all physiological states studied indicating good tissue penetration . Bioavailability was about 80% in pregnant and lactating sows . Antimicrobial secretion in milk contributed greatly to marbofloxacin elimination . These results indicate an important influence of lactation on marbofloxacin pharmacokinetics in sows . Therefore, in such cases, marbofloxacin dose should be increased during lactation. Br J Clin Pharmacol, 1993 Feb, 35(2), 199 - 203 The measurement of a new antimicrobial quinolone in hair as an index of drug exposure; Uematsu T et al.; 1 . Scalp hair samples were obtained at 1 month intervals up to 5 months from healthy male volunteers participating in a phase I study of a new antimicrobial quinolone, OPC-17116 . 2 . Hair was sectioned into 1 cm lengths from the scalp end . Corresponding portions from five pieces of hair were dissolved in 1 N NaOH and assayed for OPC-17116 by h.p.l.c . 3 . In all subjects taking a single dose (400 mg, n = 5) or repeated doses (400 mg day-1, twice daily, for 6.5 days, n = 6), the drug was detected in the portions of hair corresponding to the administration period, assuming a hair growth rate of 1 cm/month . 4 . OPC-17116 (300 mg day-1, three times daily, for 2 days) was given to four healthy male volunteers, from whom hair samples were obtained at 1 month and 3 months . The drug was detected in 1 to 4 consecutive 2.5-mm long portions of a single hair and there was no significant axial diffusion of the agent along the hair shaft with time . 5 . These findings indicate the utility of measuring this quinolone derivative in hair as an index of exposure, and as a time-marker for the hair analysis of other drugs. Am Rev Respir Dis, 1993 Feb, 147(2), 414 - 9 Inhibition of candidacidal activity of polymorphonuclear cells by alveolar macrophage-derived factor from lung cancer patients; Vecchiarelli A et al.; Culture supernatants of alveolar macrophages (AM) from lung cancer patients are able to inhibit the candidacidal activity of polymorphonuclear cells (PMN) in vitro . This phenomenon is ascribed to a factor secreted in the culture medium by unstimulated AM from tumor-bearing patients, but not from normal subjects . The inhibitor does not apparently affect the phagocytic activity of PMN, but the superoxide release during phagocytosis is significantly impaired when cells are pretreated with supernatants containing the factor . The secretion of the inhibitor seems to be restricted to the pulmonary compartment of lung cancer patients, since culture supernatants of peripheral blood monocytes (PBM) from the same subjects are not capable of depressing the candidacidal activity of PMN . The AM-derived factor is not inactivated after exposure to heat (60 degrees C) and when supernatants are analyzed by HPLC, the inhibitory activity is recovered in the fractions corresponding to a low molecular weight (800 D) . In conclusion, AM from lung cancer patients are able to produce a factor capable of inhibiting the antimicrobial activity of PMN . This could account, at least in part, for the enhanced susceptibility to local infections observed in lung cancer patients. Indian Pediatr, 1993 Feb, 30(2), 177 - 85 Risk factors for persistent diarrhea among children under 2 years of age . Case control study; Deivanayagam N et al.; A case control study was done at the Institute of Child Health, Madras, among prospectively recruited children aged 1-23 months to identify the risk factors for persistent diarrhea . Cases were children with diarrhea persisting for > 14 days . Controls were children with acute diarrhea who had recovered within 7 days . Two controls for each case, matched for age were recruited . The total number of cases and controls recruited were 170 and 340 . Fifteen risk factors for association with persistent diarrhea were studied . When the factors were adjusted for covariables by logistic regression, only 6 factors were found to be significant, namely, malnutrition (OR 2.9; 95% CI 1.9-4.5), dysenteric stools (OR 2.4; 95% CI 1.3-4.3), indiscriminate use of antimicrobials (OR 2.4; 95% CI 1.6-3.9), associated illnesses (OR 2.1; 95% CI 1.5-3.1), stools > 10/day (OR 1.8; 95% CI 1.2-2.8) and persistence of dehydration (OR 1.4; 95% CI 1.2-1.7) . However, when invasive diarrhea was excluded, weight loss during study period became a significant factor . It is concluded that all children with acute diarrhea should be investigated for associated illnesses and treated adequately, indiscriminate use of antimicrobials should be avoided and nutritional support should be provided. Curr Opin Pediatr, 1993 Feb, 5(1), 50 - 4 Upper respiratory tract infections in children; McMillan JA; Respiratory tract infections are a frequent problem for children, families, and pediatricians . Most such infections are trivial and do not warrant significant concern; however, for some children and some infections, aggressive and effective therapy is important . Much of the literature discussed in this article reflects attempts to clarify and improve appropriate use of antimicrobial therapy for those children in whom it is necessary. J Pharm Pharmacol, 1993 Feb, 45(2), 98 - 101 Kinetic evaluation of the ciliotoxicity of methyl- and propyl-p-hydroxybenzoates using factorial experiments; Jian L et al.; The ciliotoxicity of methyl-p-hydroxybenzoate (methyl paraben, MHB) and propyl hydroxybenzoate (propyl paraben, PHB) was investigated . It is shown that at the concentrations used (0.28 and 0.38 mM) PHB exerted only mild toxicity . The MHB solutions used (1.18 and 2.36 mM) were much more ciliotoxic . There was, however, an order of magnitude difference in the concentrations used as a result of constraints imposed by their differing aqueous solubilities . There was no evidence of synergism in the ciliotoxicity of the two compounds when the MHB concentration was raised from 1.18 to 2.36 mM and the PHB concentration was raised from 0.28 to 0.38 mM in a 2(2) factorial experiment . At those levels the two compounds showed additive effects . On the other hand, clear synergism was evidenced by the fact that the ciliotoxicity of both MHB and PHB was dependent on whether the cilia were exposed to each hydroxybenzoate singly or in combination . The results combined with those of an earlier study, indicate that it is not possible to improve the selectivity of antimicrobial activity without also increasing ciliotoxicity. J Antimicrob Chemother, 1993 Feb, 31(2), 289 - 302 Evaluation of the activity of a number of antimicrobial agents against mycobacteria within mouse macrophages by a radiometric method; Banerjee DK et al.; {3H}-uridine was incorporated by Mycobacterium bovis BCG with increasing intensity as the incubation period was increased . Rifampicin and isoniazid inhibited incorporation of the label rapidly . Similar inhibition was seen with M . tuberculosis H37Rv and several clinical isolates of M . tuberculosis both in axenic medium and inside macrophages . Ofloxacin and ciprofloxacin were both inhibitory but clofazimine was not . The combination of rifampicin with either isoniazid or ethambutol produced enhanced killing, but the combination of ethambutol and isoniazid was not synergic . Mycobacterium avium-intracellulare isolates from AIDS patients were less susceptible to rifampicin and were unaffected by isoniazid, ethambutol, clofazimine, ofloxacin and ciprofloxacin . The results obtained by inhibition of {3H}-uridine incorporation by intracellular mycobacteria correlated with conventional in-vitro MICs and was reproducible and rapid; a definitive result was obtainable within seven days. Pacing Clin Electrophysiol, 1993 Feb, 16(2), 303 - 8 Infected endocardial pacemaker electrodes: successful open intracardiac removal; Niederhauser U et al.; The long-term results after open intracardiac removal of infected pacing electrodes are presented . METHODS: Between 1985 and 1990 open intracardiac removal of 19 infected pacing electrodes was performed in seven patients (six male and one female), with a mean age of 56 years . The indications were: persisting bacteremia in three; generator pocket infection in four; endocarditis in one; and ventricular tachycardia caused by retracted electrodes in one . All electrodes were fixed in the right heart and extraction by closed methods failed . Percutaneous catheter techniques were not applied in these seven patients . In five patients two ventricular electrodes had to be removed, and in two patients a single one . A total of seven atrial electrodes were removed in six patients (one electrode each in five patients; two electrodes in one patient) . All atrial and two ventricular electrodes could be removed through a pursestring suture without use of a pump oxygenator . For the removal of ten ventricular electrodes in six patients (two electrodes each in four patients; 1 electrode each in two patients) a right-sided atriotomy was necessary with cardiopulmonary bypass (CPB) . Simultaneously, five new pacing systems were implanted . RESULTS: There were no early or late mortalities . In January 1991, all seven patients are alive and in a mean New York Heart Association Class 1,3 of heart failure after a mean interval of 33 months . In all cases the infection could controlled with a simultaneous antimicrobial chemotherapy and the postoperative period was free of major complications . CONCLUSION: Open intracardiac removal of retained pacing electrodes with or without use of CPB is a safe procedure without major complications . It is mandatory for all infected pacing electrodes that cannot be extracted by closed methods. MMWR Morb Mortal Wkly Rep, 1993 Jan 22, 42(2), 39 - 42 Ceftriaxone-associated biliary complications of treatment of suspected disseminated Lyme disease--New Jersey, 1990-1992; The riminophenazine agents clofazimine and B669 inhibit the proliferation of cancer cell lines in vitro by phospholipase A2-mediated oxidative and nonoxidative mechanisms; Department of Immunology, Faculty of Medicine, University of Pretoria, Republic of South AfricaClofazimine, a riminophenazine antimicrobial agent, and its analogue B669 were investigated for their effects on FaDu cells, a human squamous carcinoma cell line . These agents, at concentrations within the therapeutic range (0.25-2 micrograms/ml), caused a dose-dependent tumor cell cytotoxicosis which was greatly enhanced in the presence of human neutrophils . The neutrophil-mediated increment in tumoricidal activity, but not the direct antitumor effects of the drugs per se, was inhibited by catalase . The effects of these drugs on three more cell carcinoma lines as well as on two primary cultures and a noncarcinoma cell line were also investigated and compared with the activity of the standard antitumor chemotherapeutic agents bleomycin, cisplatin, and methotrexate . All seven cultures were sensitive to clofazimine and B669 compared to six that were sensitive to cisplatin, three that were sensitive to bleomycin, and one that was sensitive to methotrexate . The treatment of FaDu cells with clofazimine and B669 was associated with enhanced activity of phospholipase A2, as evidenced by increased release of radiolabeled arachidonate and lysophosphatidylcholine from membrane phospholipids . Inhibitors of arachidonic acid metabolism, protein kinase C inhibitors, as well as water and lipid soluble antioxidants failed to protect the cells against the cytotoxic activity of clofazimine and B669 . However, alpha-tocopherol, a lysophospholipid-complexing agent, completely blocked the antiproliferative effects of the riminophenazines and also protected the cells against the direct cytotoxic effect of lysophosphatidylcholine, while the lysophospholipid-neutralizing enzyme lysophospholipase protected against the riminophenazines . These observations demonstrate that the tumoricidal properties of clofazimine and B669 are probably due to increases in the lysophospholipid content of cell membranes. Ugeskr Laeger, 1993 Jan 11, 155(2), 83 - 5 {Endoscopic prosthetic treatment in stenosis of the choledochus caused by malignant disease}; Pedersen FM; Endoscopic insertion of a biliary endoprosthesis is often the treatment of choice in patients with malignant common bile duct obstruction . In experienced centers the procedure is combined with low risk and high success rates . A well known and unresolved problem is the tendency of the stents to clog within a few months, recessitating their replacement . The best survival of the stents is achieved by using the largest straight teflon stent without sideholes . Long-term treatment with antibiotics, antimicrobial impregnated stents, stents without side holes or intraductally placed stents might increase the survival of the stents . Great experience is necessary in order to ensure optimal endoscopic treatment of all the patients with malignant common bile duct obstruction and the treatment therefore should be performed in few large centers. J Biol Chem, 1993 Jan 5, 268(1), 522 - 6 The cDNA of the neutrophil antibiotic Bac5 predicts a pro-sequence homologous to a cysteine proteinase inhibitor that is common to other neutrophil antibiotics; Zanetti M et al.; Bac5 is a 5-kDa proline- and arginine-rich antibiotic, stored as inactive precursor (proBac5) in the large granules of bovine neutrophils . A full-length cDNA encoding the precursor form of Bac5 has been cloned . The encoded protein (pre-proBac5) has a calculated mass of 20,031 Da and a pI of 9.21 . This comprises a putative signal peptide of 29 amino acid residues and a 101-residue pro-sequence that precede the mature antibiotic . The pro-sequence is acidic and may neutralize the highly cationic Bac5, thus accounting for the inactivation of the antibiotic activity observed in in vitro experiments . The structure of mature Bac5 agrees closely with the amino acid sequence previously determined, with an additional tripeptide tail predicting carboxyl-terminal amidation . A valyl residue is deduced at the cleavage site for the proteolytic maturation of proBac5, consistent with a previous observation showing elastase as the enzyme involved in this processing step . The region upstream of Bac5 reveals high identity to corresponding regions of two neutrophil antimicrobial polypeptides, CAP18 from rabbit and bovine indolicidin . The COOH-terminal sequences of these antibiotics are completely unrelated . The proregion also exhibits remarkable similarity to pig cathelin, an inhibitor of cathepsin L, indicating a common evolutionary origin. FEBS Lett, 1993 Jan 4, 315(2), 187 - 92 Defensin-6 mRNA in human Paneth cells: implications for antimicrobial peptides in host defense of the human bowel; Jones DE et al.; The epithelial surface of the human small intestine is a barrier between the host and the microbial environment of the lumen . A human small intestine cDNA clone was found to encode a new member of the defensin family of antimicrobial peptides, named human defensin-6 . Tissue expression of this mRNA is specific for the small intestine as determined by Northern blot analysis and polymerase chain reaction analysis . In situ hybridization demonstrated that human defensin-6 mRNA localizes to Paneth cells in the crypts of Lieberkuhn . The finding of an abundant defensin mRNA in human Paneth cells supports the notion that these epithelial cells may play a key role in host defense of the human bowel . The results also strengthen the hypothesis that peptide-based host defenses are prevalent at mucosal surfaces in mammals. Clin Ther, 1993, 15 Suppl A, 37 - 43 Antibiotic cost control measures in a hospital pharmacy; Manzo J et al.; Faced with rising drug costs and an increase in type-1 beta-lactamase resistance, hospitals have been looking for ways to contain antibiotic costs while continuing to provide quality medical care . The hospital pharmacy at Montefiore Medical Center, Moses Division, has developed a number of programs aimed at identifying antibiotic prescribing trends and minimizing costs . An antimicrobial susceptibility cascade reporting (ASCR) system is used to consolidate and target antimicrobial susceptibility information available to the staff physicians . All antibiotics are tested in the microbiology laboratory for susceptibility; however, physicians receive susceptibility reports only for the more cost-effective, conventional antibiotics . Broader-spectrum, more powerful, and usually more expensive antibiotics are not reported with the ASCR system unless resistance to the more cost-effective antibiotics is noted . Two other reforms initiated are expansion of the pharmacy-based intravenous additive program to include antibiotics and the implementation of a drug therapy enhancement program authorizing automatic conversion by the pharmacist of targeted drug regimens to more clinically rational, cost-effective regimens. Folia Microbiol (Praha), 1993, 38(1), 40 - 2 Antimicrobial effects of some dicarbonyl and tricarbonyl sugar hydrazone derivatives; Gabriel J et al.; Several dicarbonyl and tricarbonyl sugars were prepared by the use of fungal enzymes and the antimicrobial effects of their N,N-diphenylhydrazine derivatives were tested . G+ bacteria were more sensitive than G- bacteria especially in the group of disubstituted compounds . Peracetyled derivatives were not active . No inhibition of yeast growth was found. J Indian Med Assoc, 1993 Jan, 91(1), 10 - 3 Chloramphenicol resistant enteric fever; Chakravorty B et al.; In recent times there have been several reports of chloramphenicol resistant enteric fever necessitating the use of other antimicrobial agents . Clinical profile of 15 chloramphenicol resistant patients of enteric fever was studied . Three such patients (20%) responded to chloramphenicol despite in vitro resistance to the drug . Hence chloramphenicol still remains the drug of first choice in enteric fever as a majority (68.4%--26 out of 38) of our bacteriologically proven enteric fever patients were cured by the drug . The remaining 12 cases responded satisfactorily to ciprofloxacin (46.7%), gentamicin (20%), and ofloxacin (13.3%) . There was an increased incidence of complications among the 15 drug resistant cases as compared to 23 cases of chloramphenicol sensitive enteric fever observed during the same period. Cancer Chemother Pharmacol, 1993, 32(2), 109 - 15 Identification of serum components that inhibit the tumoricidal activity of amphiphilic alpha helical peptides; Peck-Miller KA et al.; Antimicrobial peptides that can form amphiphilic alpha helices were tested for their ability to lyse various human tumor cell lines in vitro . These peptides include C18G, whose sequence is a derivative of the carboxyl terminus of human platelet factor IV, and 399, an idealized amphiphilic alpha helix . Both peptides exhibited potent antitumor activity against all cell lines tested, unlike magainin 2, a naturally occurring antimicrobial peptide of similar structure, which was relatively inactive under the same conditions . Also, the lytic activity of C18G is specific for tumor cells versus human red blood cells . The effects of serum can be important when evaluating the potency of lytic peptides, since other tumoricidal peptides have been shown to be completely inactivated by low serum levels . Experiments with C18G and 399 revealed that their activity was indeed reduced in the presence of human serum, but that significant lytic activity remained even at relatively high serum concentrations . Various serum components were tested for their inhibitory activity . Whereas albumin and high-density lipoprotein had only slight inhibitory properties, low-density lipoprotein was found to be a potent inhibitor of peptide-mediated cell lysis . The peptide 399, which is more sensitive to serum inhibition than C18G, also binds more extensively to all serum components tested. Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S61 - 7 Liposomes as carriers of antimicrobial agents or immunomodulatory agents in the treatment of infections; Bakker-Woudenberg IA et al.; Targeting of antimicrobial agents by means of liposomes is under investigation and may be of importance in the treatment of infections that prove refractory to conventional forms of antimicrobial treatment . The ability to achieve a significantly longer residence time of liposomes in plasma and limited uptake of liposomes by the mononuclear phagocyte system opens up new areas of investigation and potential therapeutic application . By manipulating the liposomal composition, rates of uptake and intracellular degradation can be influenced and thereby the rates at which liposome-encapsulated agents are released and become available to exert their therapeutic action . With respect to the targeting of macrophage modulators at the mononuclear phagocyte system by means of liposomes for maximal stimulation of the nonspecific antimicrobial resistance, experimental evidence is now available of the potential usefulness of liposomes as carriers of these agents . This approach may also be of importance for the potentiation of treatment of severe infections. Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S55 - 7 Relevance of animal models for clinical treatment; Craig W; The use of animal models has become an integral part of the evaluation of drugs for antimicrobial chemotherapy . Animal models can be used to define the penetration of antimicrobial agents at foci of infections, the time course of in vivo antimicrobial therapy, dose-response relationships, and the influence of therapy on the pathophysiologic consequences of infection . Animal models have been useful in the delineation of many of the basic principles currently used in clinical practice and in the selection of new agents and new therapeutic approaches for clinical trials in humans . In spite of the many positive aspects of animal models, several problems, such as altered pharmacokinetics in animals, can preclude direct application of results to clinical practice . Studies in animal models cannot replace the need for human clinical trials. Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S49 - 54 The value of new antimicrobial agents; Wagenvoort JH; New antimicrobial agents require careful assessment to determine whether they possess the appropriate properties for clinical use . Many new compounds of value in the prophylaxis and therapy of infections have been included in the current armamentarium . Close monitoring to identify possible adverse effects of new agents is essential . Alternative uses of older agents also expands therapeutic opportunities in the combat against infectious diseases . Inappropriate use of antimicrobial agents contributes to the worldwide problem of increasing bacterial resistance . The dramatic spread of such bacterial strains is partially responsible for the rising costs of infectious diseases . A rational and strict antibiotic policy is thus of great importance for the optimal use of these agents. Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S42 - 8 Fungal and bacterial infections in the immunocompromised host; Rubin RH; As the number of immunocompromised patients increases due to the spread of the AIDS epidemic and the successes being achieved with transplantation, cancer chemotherapy and immunosuppressive therapy, increased attention is being turned to the prevention and treatment of the infections that afflict these individuals . The risk of infection in these patients is determined by the interaction between the epidemiologic exposures that the patient experiences and the net state of immunosuppression (the greater the exposure, the greater the chances of infection even in an immunologically competent individual; the greater the net state of immunosuppression, the greater the chances of infection even with minimal exposures) . The bacterial and fungal infections that affect these patients are reviewed and strategies of antimicrobial management defined, recognizing that there are three modes of use of antimicrobial agents in these patients: therapeutic administration to treat clinical infection, and prophylactic and pre-emptive administration to prevent or abort clinical infection . These last two are of particular importance in this patient population because the prime aim of the infectious disease clinician in dealing with these problems is the prevention of clinical disease. Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S31 - 5 Anatomical barriers for antimicrobial agents; Barza M; It is often suggested that there are substantial anatomic barriers to the passage of antibiotics from the circulation into tissues and fluids of the body . In fact, most capillary beds are fenestrated and allow the passage of antimicrobial agents into tissue fluids fairly readily . At equilibrium, the mean concentrations of free (unbound) antibiotic in plasma and tissue fluids over the dosing interval are equal . However, the time to achieve equilibrium may range from minutes to days, depending on the ratio of surface area to volume of the tissue fluid compartment . There are several sites in the body in which nonfenestrated capillary beds pose appreciable barriers to the diffusion of antibiotics, namely the central nervous system, the eye and the prostate gland . Only lipid-soluble drugs traverse these capillaries readily . If the nonporosity of the capillaries were the only barrier to drug diffusion in these sites, the mean concentrations would eventually be equal to those in the plasma . However, in the central nervous system and the retina of the eye, transport pumps for organic anions combine with the effect of nonporous capillaries to produce concentrations which, even at equilibrium, are lower than those in the plasma . Bulk flow may also play a role in lowering drug concentrations in the cerebrospinal fluid . In the prostate gland, pH partition may cause mean concentrations in the prostatic secretions to differ from those in the plasma at equilibrium. Annu Rev Immunol, 1993, 11, 105 - 28 Defensins: antimicrobial and cytotoxic peptides of mammalian cells; Lehrer RI et al.; Defensins are antimicrobial and cytotoxic peptides that contain 29-35 amino acid residues, including six invariant cysteines whose intramolecular disulfide bonds cyclize and stabilize them in a complexly folded, triple-stranded beta-sheet configuration . Generated by the proteolytic processing of 93-95 amino acid precursor peptides, the constitute > 5% of the total cellular protein in human and rabbit neutrophils (polymorphonucleated neutrophils--PMN) and are also produced by rabbit lung macrophages and by mouse and rabbit small intestinal Paneth cells . Despite their prominence in rat PMN, defensins are not found in murine PMN . The antimicrobial spectrum of defensins includes gram positive and gram negative bacteria, mycobacteria, T . pallidum, many fungi, and some enveloped viruses . Defensins exert nonspecific cytotoxic activity against a wide range of normal and malignant targets, including cells resistant to TNF-alpha and NK-cytolytic factor . They appear to kill mammalian target cells and microorganisms by a common mechanism, which involves initial electrostatic interactions with negatively charged target cell surface molecules (likely the head groups of polar membrane lipids), followed by insertion into the cell membranes which they permeabilize, forming voltage-regulated channels . In addition to their antimicrobial and cytotoxic properties, some defensins act as opsonins, while others inhibit protein kinase C, bind specifically to the ACTH receptor and block steroidogenesis or act as selective chemoattractants for monocytes . Defensins are a newly delineated family of effector molecules whose contribution to host defense, inflammation, and cytotoxicity may be considerable for humans, even though it is unlikely to be revealed by experimentation with mice. Arch Inst Cardiol Mex, 1993 Jan-Feb, 63(1), 47 - 51 {The treatment of infectious endocarditis . Cefotaxime versus "traditional" medical management}; Felipe Flores L et al.; We performed an open study to compare efficacy and renal toxicity of cephotaxime versus the usual beta lactam plus aminoglucoside treatment of infectious endocarditis . Twenty cases were studied, 10 treated with cephotaxime 4 g/day per 21 days and aminoglucoside for only 10 days . Comparison group received a combination of different beta lactam antibiotic plus aminoglucoside for 21 to 50 days, these patients were under care of nonparticipant physicians . Although cephotaxime treatment was as good as conventional antimicrobial scheme for control of infectious endocarditis, the treatment cost increases, and there is only marginal benefit in regard renal toxicity. Enferm Infecc Microbiol Clin, 1993 Jan, 11(1), 29 - 32 {Prevalence of serotype 0:12 among strains of P . aeruginosa causing nosocomial infection in Spain (1980-1991)}; Vindel A et al.; BACKGROUND: The aim of the present study was to characterize P . aeruginosa strains causing nosocomial infection in Spain between 1980-1990 with special emphasis on the incidence of serotype 0:12 strains . METHODS: 11,411 strains of P . aeruginosa from hospital-acquired infections were studied and epidemiologically characterized by phage-typing, serotyping and sensitivity to antimicrobial agents . The strains of the 0:12 serotype were analyzed by isoenzyme analysis . RESULTS: Although the major serotypes throughout the period studied were: 0:1, 0:6 and 0:11, the existence of serotype 0:12 strains (6%) were detected which had produced nosocomial outbreaks in surrounding countries . This serotype is homogeneous in that the epidemiologic markers and patterns of sensitivity to antibiotics and the multienzyme analysis demonstrate uniformity in the electrophoretic patterns of all the strains studied . CONCLUSIONS: The 0:12 serotype is in Spain indistinguishable by phage typing and studies of antibiotic sensitivity . It may be considered as being of clonal origin and is probably equal to that existing elsewhere in Europe. Clin Microbiol Rev, 1993 Jan, 6(1), 57 - 68 Gram-negative sepsis: a dilemma of modern medicine; Bone RC; Gram-negative sepsis is an increasingly common problem, with up to 300,000 cases occurring each year in the United States alone . Despite the ongoing development of new antibiotics, mortality from gram-negative sepsis remains unacceptably high . To stimulate earlier therapeutic intervention by physicians, a new set of broad definitions has been proposed to define the systemic inflammatory response characteristic of sepsis . In this review, the signs and symptoms of this progressive, injurious process are reviewed and its management is discussed, as are the mechanisms by which bacterial endotoxin triggers the biochemical events that lead to such serious complications as shock, adult respiratory distress syndrome, and disseminated intravascular coagulation . These events often occur even when appropriate antimicrobial therapy has been instituted . An increased understanding of the structure of endotoxin and its role in the development of sepsis, together with advances in hybridoma technology, has led to the development of monoclonal antibodies that bind to endotoxin and significantly attenuate its adverse effects . These agents promise to substantially reduce the morbidity and mortality associated with gram-negative sepsis. APMIS, 1993 Jan, 101(1), 27 - 32 In vitro antimicrobial susceptibility testing of rapidly growing mycobacteria using the tablet diffusion method: resistance pattern of Norwegian Mycobacterium fortuitum and Mycobacterium chelonae isolates; Hoel T et al.; Thirty-one Norwegian clinical isolates of rapidly growing mycobacteria classified as Runyon's group IV, including 20 Mycobacterium fortuitum and 11 Mycobacterium chelonae strains, were found resistant to a majority of tuberculostatic agents . Minimal inhibitory concentration (MIC) was determined for twelve other antimicrobial agents: amikacin, tobramycin, streptomycin, cefoxitin, imipenem, norfloxacin, ciprofloxacin, doxycycline, erythromycin, fusidic acid, co-trimoxazole and capreomycin . The agar plate dilution method was employed and compared with the agar tablet diffusion method . Regression lines were established correlating MIC values and inhibition zones . The agar tablet diffusion method was found to be a simple and useful method for testing antimicrobial susceptibilities of M . fortuitum and M . chelonae, and a good correlation between MIC values and zone sizes with twelve antimicrobial agents was revealed . Correlation coefficients for most of these antimicrobial agents were around -0.90 . M . chelonae was generally more resistant than M . fortuitum . Four antimicrobial agents, capreomycin, norfloxacin, ciprofloxacin and amikacin, showed differences between M . fortuitum and M . chelonae large enough to allow the zone diameter to be used diagnostically. Agents Actions Suppl, 1993, 39, 225 - 9 Doxycycline protects serum alpha-1-antitrypsin from human neutrophil collagenase; Sorsa T et al.; Interstitial collagenases, members of the matrix metalloproteinase family, are key initiators of collagen destruction during various disorders such as rheumatoid arthritis . Recently interstitial collagenases were found to efficiently degrade an additional non-collagenous substrate, the serum alpha-1-antitrypsin (AAT also called alpha-1-proteinase inhibitor or serpin) . Serpins are major endogenous inhibitors of serine proteinases, particularly neutrophil elastase . Of relevance to neutrophil-mediated collagen degradation, the tetracycline family of antibiotics are now known to inhibit inhibit mammalian collagenases by a mechanism unrelated to their antimicrobial activity . This study identifies an additional mechanism by which tetracyclines may retard tissue breakdown during inflammatory diseases . Doxycycline, added to the reaction mixture as in concentrations as low as 10 microM, which correspond to levels of the drug readily achieved in vivo, produced detectable inhibition of serpinase activity of neutrophil collagenase, although levels of 50-100 microM or greater were required to reduce AAT degradation more than 75% . The concentration of doxycycline to inhibit 50% (IC50 of serpinase activity) of AAT degradation by neutrophil collagenase was found to approximate 20 microM, a value similar to the IC50 for doxycycline required to inhibit collagen degradation by neutrophil collagenase . Doxycycline was also found to inhibit at cell level neutrophil-mediated degradation of AAT . The protection of bodies' AAT-shield from serpinolytic activity of collagenase would result in inhibition of serine proteinases such as neutrophil elastase . Tetracyclines may thus protect matrix constituents from a wider spectrum of neutral proteases than previously recognized, not just from the matrix metalloproteinases collagenase and gelatinase. J Vet Intern Med, 1993 Jan-Feb, 7(1), 4 - 11 Nocardiosis . A literature review with selected case reports in two dogs; Marino DJ et al.; Two dogs with systemic nocardiosis are presented and the pathobiology, diagnosis, and treatment of nocardial infections are discussed . Both dogs had nonspecific respiratory signs and depression . The diagnosis was made by isolation of the organism only after surgical drainage was established and appropriate tissues were cultured . The response to surgical drainage and antimicrobial therapy was dramatic in both dogs, but one dog experienced a drug reaction to trimethoprim-potentiated sulfonamide . Although systemic nocardial infections traditionally have had a grave prognosis, through early diagnosis, surgical intervention, and the use of newer, safer and synergistically acting antimicrobials, the prognosis has improved . This article reviews current human and veterinary literature regarding the microbiology, pathogenesis, and treatment of nocardiosis and reports on the successful treatment of systemic nocardiosis in two dogs. J Prosthet Dent, 1993 Jan, 69(1), 102 - 5 A study of the antimicrobial properties of impression tray adhesives; Herman DA; Three impression tray adhesives were tested for their antimicrobial actions on three bacteria strains used for disinfectant studies . The colony forming unit (CFU) counts from plating the adhesive-exposed bacteria showed a significant reduction in number compared with the CFU of the controls . Statistical analyses confirmed the significant reduction (p < 0.05) for all but one test case . Proper infection control procedures should always be followed, but the added benefits of disinfection by impression tray adhesives can help prevent cross contamination. J Biomater Appl, 1993 Jan, 7(3), 265 - 76 Bioactive polymers 68--controlled release of neomycin-furazolidone bicomponent system from xanthan hydrogel; Dumitriu S et al.; The neomycin-furazolidone-xanthan complex has been synthesized . Neomycin is covalently linked to xanthan, while furazolidone is inserted in the hydrogel formed by the reaction between neomycin and xanthan . The content of neomycin and furazolidone depends on the drug rate in the reaction medium . Thus, a zero-order kinetics is obtained for the release of both neomycin and furazolidone in basic medium . The complex's antimicrobial activity is intensified. J ET Nurs, 1993 Jan-Feb, 20(1), 21 - 5 Characteristics and prevention of wound infection; Corum GM; This article provides an overview of bacterial wound infection . It examines definitions of infection, types and concentrations of bacteria in wounds at different stages of healing, and the significance of osteomyelitis and sepsis in deep, necrotic ulcers . It also describes the culturing of wounds and examines the use of topical antimicrobials, debridement, irrigation, and occlusive dressings . Factors in surgical wound infection and infection control are examined . Finally, systemic factors are summarized. Zentralbl Gynakol, 1993, 115(2), 80 - 2 {Cefuroxime and cefoxitin in perioperative preventive use of antibiotics . A randomized study}; Hoyme UB et al.; In a prospectively randomized study 243 patients scheduled for gynaecologic surgery received either 2 g Cefoxitin or 1.5 g Cefuroxim at induction of anaesthesia . Both drugs were well tolerated by all study patients . Post-operative fever was seen in seven women in the Cefuroxim group (n = 121) vs . three women in the Cefoxitin group (n.s., x2-test) . Wound infection occurred in two women in each group . In result Cefuroxim probably can be recommended as an alternative replacing Cefoxitin in prophylaxis, so Cefoxitin can be reserved as potent antimicrobial substance for therapy of gynaecologic infections. Zentralbl Gynakol, 1993, 115(2), 77 - 9 {Perioperative preventive use of antibiotics in breast surgery: clindamycin vs . cefuroxime}; Hoyme UB et al.; 149 patients scheduled for breast surgery with an identified risk for infection received either 1.2 g Clindamycin (n = 79) or 1.5 g Cefuroxim given intravenously in a prospectively randomized fashion at induction of anaesthesia . Both drugs were well tolerated by all study patients . Postoperative fever was seen in one woman in the Clindamycin group vs . two women in the Cefuroxim group (n.s.) . Serum and tissue levels measured 30 minutes after administration were within the therapeutic range for both antimicrobial substances. Infection, 1993 Jan-Feb, 21(1), 49 - 53 Timing, dosing and duration of antimicrobial prophylaxis in urology: a study in guinea pigs with special reference to high-risk conditions; Gasser TC et al.; A study in guinea pigs was performed to investigate the importance of timing, dosage and duration of antimicrobial prophylaxis in urologic surgery . To simulate high-risk conditions, in one group a foreign body was implanted subcutaneously . The prostate and one kidney were cauterized and bacteremia was induced by intravenous injection of an Escherichia coli suspension . Various ciprofloxacin regimens were tested . The results indicate that antimicrobial prophylaxis is beneficial only if administered before or shortly after surgery . Full therapeutic dosage may not be necessary for prophylactic efficacy . Single-dose prophylaxis was as effective as multiple doses . Foreign body infection could be prevented by single-dose prophylaxis. Chem Pharm Bull (Tokyo), 1993 Jan, 41(1), 148 - 55 Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives; Yamane T et al.; As a part of our studies on the syntheses of benzoxazinorifamycin derivatives, 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives were synthesized, and tested for their antimicrobial activities . The antimicrobial activities of these compounds against gram-positive and gram-negative bacteria were almost identical to those of rifampicin (RFP) and rifabutain (RFB), however, antimicrobial activities against Mycobacterium tuberculosis were superior to RFP, while being similar to RFB . 3'-Hydroxy-5'-(4-alkyl-1-piperazinyl)benzoxazinorifamycin derivatives also had in vitro potent activities against Mycobacterium avium complex (MAC) . Their minimal inhibitory concentration values against MAC were 2-256 times greater than RFP and RFB . Their in vivo efficacies against M . tuberculosis and MAC, after oral administration to mice, were superior to RFP and RFB, except for RFB against M . tuberculosis activity in vivo . Although they were absorbed from the gastrointestinal tract, their plasma levels were lower than that of RFP . Among these 5'-(4-alkyl-1-piperazinyl) derivatives, 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin, compound 19 (KRM-1648), was selected as the most promising and its preliminary pharmacokinetic characteristics in mice were investigated . Compound 19 was distributed much more in tissues, especially in spleen and lung, than in plasma and had a long elimination time from tissues. J Antimicrob Chemother, 1993 Jan, 31(1), 65 - 71 The E test for antimicrobial susceptibility testing of Helicobacter pylori; Cederbrant G et al.; Antimicrobial susceptibility testing of Helicobacter pylori by conventional means (disc diffusion) is of questionable value because the bacterium grows so slowly . We have determined the susceptibilities of 20 isolates of H . pylori to ampicillin, erythromycin, gentamicin, metronidazole, rifampicin and tetracycline by the E test, a novel technique for measuring MICs, and compared the results with those determined by standard agar dilution and disc diffusion methods . Eighty-one per cent of E test-determined MICs were within one two-fold dilution and 93% were within two two-fold dilutions of those determined by the reference agar dilution method . MICs determined by the E test were highly reproducible; replicate results were invariably within one two-fold dilution . MICs were not affected by the size of the inoculum, preincubation or incubation times . Regression lines for disc diffusion could not be determined because of the lack of resistant strains . However, metronidazole-resistant strains (MIC > 32 mg/L) were easily distinguishable from susceptible strains (MIC < 1 mg/L) . In conclusion, the E test is a reliable method for determining the antimicrobial susceptibility of H . pylori. Food Chem Toxicol, 1993 Jan, 31(1), 53 - 8 Nitrosation of the antimicrobial drug hexetidine: nitrosamines derived from a triamine decomposition product; Mende P et al.; Five new nitrosamines were identified as nitrosation products of N1,N3-bis(2-ethylhexyl)-2-methyl-1,2,3-propantriamine, a hydrolysis product usually found in preparations of the antimicrobial drug hexetidine . All nitrosamines are formed after deamination of the primary amino group by nitrosation of one of the two secondary amino groups . The propantriamine derivative is very easily nitrosatable, with total nitrosamine yields in the upper range of a comparative scale of drug nitrosatability. Int J Pediatr Otorhinolaryngol, 1993 Jan, 25(1-3), 19 - 24 |