Antimicrobial

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
Prophylaxis for recurrent acute otitis media: a Brazilian study; Sih T et al.; We enrolled 60 children with recurrent acute otitis media (AOM) in a study of the effectiveness of antimicrobial prophylaxis . All children were entered into the study following an acute episode of infection treated with amoxicillin (AMX) for 10 days . Following therapy, the children were re-examined, and then randomly assigned to receive either trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin (AMX) or a placebo (PLA) . Twenty children were included in each group . Each drug was administered once a day at bedtime, at 1/3 the therapeutic dose, for 3 months . Children were re-evaluated with pneumootoscopy during episodes of acute illness and with pneumootoscopy and impedance tympanometry (TYMP) at monthly intervals . We observed a significantly increased rate of recurrent AOM in children receiving placebo compared with those who received antibiotics (50% vs . 17% P < 0.005) . Both prophylactic antibiotics were equally effective in preventing recurrent AOM (recurrence rate 20% TMP-SMX, 15% AMX) . We also observed that recurrences in children receiving placebo occurred earlier in the study period than in those receiving antibiotics . These results suggest that antimicrobial prophylaxis in children with recurrent acute otitis media is effective in reducing subsequent disease . The similar efficacy of both antibiotics tested suggests that the less expensive agent should be used.

Eur J Haematol, 1993 Jan, 50(1), 11 - 6
Synovial-type (group II) phospholipase A2 in serum of febrile patients with haematological malignancy; Rintala EM et al.; Elevated concentrations of synovial-type (group II) phospholipase A2 (PLA2-II) in serum are associated with septic bacterial infections . We measured the concentrations of PLA2-II in serum in 24 fever episodes involving patients suffering from haematological malignancies and having fever after cytotoxic treatment . We applied a novel time-resolved fluoroimmunoassay using a polyclonal antibody raised against recombinant human synovial-type PLA2 . The concentrations of PLA2-II in serum were 194.7 +/- 204.4 micrograms/l (mean +/- SD, median 141.9, range 4.6-931.5 micrograms/l) . The concentrations of PLA2-II correlated well to the concentrations of C-reactive protein (CRP) in serum (r = 0.688, p < 0.001) . The PLA2-II concentrations increased faster than the corresponding CRP values and began to decrease 12 hours after the beginning of antimicrobial treatment . Inverse correlations were found between the concentrations of PLA2-II and blood neutrophil and platelet counts . No correlation was found between the concentrations of PLA2-II and the duration of the time interval from the onset of preceding cytotoxic and corticosteroid treatment to the first blood sample . The concentration of pancreatic PLA2 was within the reference interval in all samples . The present results indicate that PLA2-II resembles an acute-phase protein and is not of blood cell or pancreatic origin.

Res Vet Sci, 1993 Jan, 54(1), 86 - 93
Comparative pharmacokinetics of aditoprim in milk-fed and conventionally fed calves of different ages; Sutter HM et al.; Aditoprim body disposition was described after intravenous and oral administration of 5 or 10 mg kg-1 bodyweight to milk-fed and conventionally fed calves with bodyweights of 80 kg, 160 kg and 210 kg . After intravenous administration to conventionally fed calves, aditoprim total body clearance increased and elimination half-life decreased with age . Oral administration of aditoprim with feed was associated with a longer absorption half-life and consequently longer elimination half-life in the older calves, because the drug was deposited in a functionally mature rumen . The weak base aditoprim is slowly absorbed from the rumen according to the pH partition hypothesis and probable binding to dietary fibres and other macromolecules . The favourable pharmacokinetics of aditoprim indicate a potential use for this antimicrobial in bovine practice, pending further studies on residue depletion profile, safety and therapeutic efficacy.

Ann Pharmacother, 1993 Jan, 27(1), 40 - 2
Maternal noncompliance with antibiotics during breastfeeding; Ito S et al.; OBJECTIVE: To determine the incidence of antibiotic prescription failure in breastfeeding women, and to characterize breastfeeding patterns during antibiotic therapy . DESIGN: Prospective cohort study by telephone follow-up of 203 breastfeeding women who were prescribed antibiotics as monotherapy . SETTING: A teratogen/drug information service (the Motherisk Program) in a tertiary care, pediatric hospital in Toronto, Canada . MAIN OUTCOME MEASURES: Number of breastfeeding women who did not initiate the antimicrobial therapy, and breastfeeding patterns during therapy in women who started it . RESULTS: Of 203 breastfeeding women who consulted the Motherisk Program for information about the safety of antimicrobials during breastfeeding, 125 (62 percent) were followed within 32 weeks (median 11) . Nineteen of the 125 (15 percent) did not initiate the antimicrobial therapy . Of the remaining 106 women, 7 (7 percent) stopped breastfeeding during therapy . Despite reassuring advice, 1 in 5 women either did not initiate therapy or did not continue breastfeeding . CONCLUSIONS: Physicians should be aware of the substantial rate of noncompliance with drug regimens among nursing women and the potential negative impact of drug therapy on breastfeeding.

Bioconjug Chem, 1993 Jan-Feb, 4(1), 54 - 62
Copolymers of lysine and polyethylene glycol: a new family of functionalized drug carriers; Nathan A et al.; Poly(PEG-Lys), a new, water-soluble poly(ether urethane), derived from L-lysine and poly(ethylene glycol) was investigated as a precursor for the preparation of polymeric drug conjugates . To facilitate a wide variety of coupling chemistries, the pendent carboxyl groups of poly(PEG-Lys) were converted to other reactive functional groups (amino, hydroxyl, active ester, and aldehyde) in high yield . These reactive pendent chains were then used as anchors for the covalent attachment of penicillin V and cephradine, two clinically used antimicrobial agents . Coupling to the carrier was achieved in good yields and the chemical versatility of this system was demonstrated by the preparation of conjugates having antibiotic ligands linked via biostable or biodegradable linkages to the carrier, either directly or via a spacer . Conjugate 4, poly(PEG-Lys-penicillin V ester), was obtained by linking penicillin V to the polymer backbone via hydrolytically labile ester bonds . This conjugate exhibited activity similar to that of the parent drug against three clinically important strains of bacteria . Drug activity coincided with the release of the drug from the carrier . Hydrolytically stable cephradine-containing conjugates were prepared by three different coupling methods but showed no antibiotic activity . 14C-labeled poly(PEG-Lys) was injected into mice and its biodistribution was monitored for 48 h . The carrier showed no preferential uptake by liver, spleen, or kidney . No signs of acute toxicity were evident in mice or rats when poly(PEG-Lys) was administered iv and ip at doses up to 10 g/kg . These results indicate that poly(PEG-Lys) is a promising precursor for the preparation of soluble drug conjugates.

Antimicrob Agents Chemother, 1993 Jan, 37(1), 67 - 70
In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method; Tomioka H et al.; MICs of a newly developed benzoxazinorifamycin derivative, KRM-1648, for Mycobacterium avium complex (MAC) were determined by the BACTEC 460 TB system and compared with those of other known antimicrobial agents . The radiometric method gave a fast, accurate, and reproducible MIC for each antimicrobial agent . MICs of KRM-1648 for 30 strains of MAC (10 strains each of M . avium isolated from AIDS and non-AIDS patients and of Mycobacterium intracellulare isolated from non-AIDS patients) were measured . The MICs, ranging from 0.004 to 0.0625 microgram/ml, were the lowest of all tested drugs, including rifampin, rifabutin, streptomycin, kanamycin, isoniazid, ethambutol, ofloxacin, ciprofloxacin, sparfloxacin, and clarithromycin . The MICs were 2 to 512 and 1 to 32 times lower than those of rifampin and rifabutin, respectively . With rifampin and ethambutol, there were some differences between the MICs for M . avium isolated from AIDS patients (American) and those for M . avium from non-AIDS patients (Japanese) . Moreover, appreciable differences between the MICs of some drugs against M . avium and M . intracellulare isolated from non-AIDS patients were found . Many strains of M . avium were more susceptible to ofloxacin than M . intracellulare, but, conversely, M . avium was more resistant to rifampin, streptomycin, ethambutol, and clarithromycin than M . intracellulare.

Antimicrob Agents Chemother, 1993 Jan, 37(1), 1 - 7
Use of rifampin in nonstaphylococcal, nonmycobacterial disease; Morris AB et al.; Rifampin has very broad antimicrobial properties with in vitro activities against many bacteria, mycobacteria, higher bacteria, chlamydia, fungi, parasites, and viruses (Table 1) . The clinical use of rifampin is more limited, in part because of the lack of in vivo human clinical studies demonstrating its efficacy . Investigators have valid concerns regarding the emergence of resistance of mycobacteria if widespread use of rifampin becomes common, although this has not been well documented . Because rifampin obtains therapeutic levels intracellularly and is distributed widely throughout the body, the antibiotic potentially could be used on a broader scale, but more studies will be needed to demonstrate its clinical utility.

Am Pharm, 1993 Jan, NS33(1), 29 - 35
Update on otitis media . Part 2 . Treatment; Sagraves R et al.; Currently the treatment of choice for OM is an oral antimicrobial agent, but selecting a specific agent should include consideration of efficacy, adverse effect profile, compliance, and cost . The use of adjunctive medications like decongestants for specific subtypes of OM has been debated in the literature, but efficacy has not been proven . As knowledge about the pathogenesis of OM is further refined, new treatment modalities for OM will be introduced . Because pharmacists are involved daily with pediatric patients who experience OM, they have an important role in making sure that patients receive appropriate therapy . A patient's profile should be checked for allergies and concurrent medications when a prescription for an antimicrobial agent is presented for a child with OM . The parents should be counseled about the administration, storage, and general product use as well as potential adverse effects, duration of use, and the need for compliance . An administration device for drug delivery like an oral syringe should be provided . Parents need advice from the pharmacist in making sure their children receive the best possible pharmaceutical care.

Clin Pharm, 1993 Jan, 12(1), 34 - 48
Helicobacter pylori and peptic ulcer disease; Ateshkadi A et al.; The role played by Helicobacter pylori in the pathogenesis of peptic ulcer disease (PUD) is discussed, and the epidemiology, identification, diagnosis, eradication, and treatment of H . pylori infection are reviewed . Isolation of H . pylori from up to 100% of patients with duodenal ulcer and 80% of patients with gastric ulcer establishes a strong association between H . pylori and idiopathic PUD, although other factors also may be essential for the development of PUD . Invasive procedures for diagnosis of H . pylori infection include upper endoscopy and biopsy of gastroduodenal tissues followed by culture or the rapid urea test; noninvasive tests include the urea breath tests and serology . Although H . pylori is susceptible to a number of antimicrobials, eradication (as opposed to suppression) of this organism has been a major challenge . The most important predictive factor for clinical and microbiological efficacy is the pretreatment susceptibility of H . pylori to nitroimidazoles . Triple therapy with bismuth, metronidazole, and either amoxicillin or tetracycline has resulted in better clinical and microbiological outcomes than either monotherapy or dual therapy . Possible adverse effects of this regimen include nausea, vomiting, taste disturbance, and diarrhea . Anti-H . pylori therapy should be reserved for those patients who have recurrent symptomatic or intractable PUD . Currently, the regimen of choice includes bismuth, metronidazole, and either amoxicillin or tetracycline given for at least two weeks.

J Acquir Immune Defic Syndr, 1993, 6 Suppl 1, S61 - 7
Immune modulation in HIV infection: fact or fantasy?
Benson EM.
Since the recognition of AIDS a decade ago, many have postulated that immune modulators would provide the therapeutic intervention necessary for preventing disease progression and death . However, despite rapid advances in our understanding of disease pathogenesis and significant achievements in the area of antiviral development, immune modulators remain largely the subject matter of philosophical editorials rather than of definitive efficacy studies . More than 50 agents have been examined to date, yet only the colony-stimulating factors have proved useful in neutropenic patients with infection with human immunodeficiency virus (HIV) . Other agents, such as isoprinosine, have provided conflicting data, whereas immunosuppressive agents, such as pentoxifylline, are presently under study . Cytokines examined prior to the development of antiviral agents were disappointing . Further studies examining these cytokines in conjunction with antiviral agents may be more rewarding . Other applications of these agents may be as adjuvants with vaccine administration or antimicrobial agents in the setting of opportunistic infection . To date, however, the data would suggest that there will be greater advantages from antiviral agents that prevent the development of immunosuppression than with immunopotentiators, which try to boost the embattled immune system.

Vet Clin North Am Small Anim Pract, 1993 Jan, 23(1), 91 - 100
Feline neonatal sepsis; Hoskins JD; When bacterial infections exceed or overcome the ability of a kitten's immune system to provide protection, life-threatening illnesses such as neonatal sepsis often occur . Many kittens with neonatal sepsis show unusual presentations or a wide variety of clinical presentations that may not be immediately recognized as being associated with sepsis . Because neonatal sepsis causes unexpected sudden death, kittens suspected of having sepsis should be treated immediately . In most instances, initial antimicrobial therapy is selected empirically . Kittens are treated by giving intravenous or intraosseous fluids for dehydration, oxygen to counter tissue hypoxemia, and glucose if hypoglycemia is present . The beta-lactam antimicrobial agents such as the penicillins, cephalosporins, and the combination of beta-lactam antimicrobials and beta-lactamase inhibitors are considered to be the first choice in the treatment of any septicemic kittens.

J Clin Gastroenterol, 1993 Jan, 16(1), 52 - 4
Leptospirosis with acute acalculous cholecystitis and pancreatitis; Monno S et al.; Severe Leptospira autumnalis infection was associated with acute acalculous cholecystitis and pancreatitis in a 66-year-old man . He was successfully treated with antimicrobial agents and supportive therapy, including hemodialysis . We review these uncommon manifestations and the effectiveness of antimicrobial therapy in advanced leptospirosis.

Am Rev Respir Dis, 1993 Jan, 147(1), 38 - 44
Follow-up protected specimen brushes to assess treatment in nosocomial pneumonia; Montravers P et al.; To prospectively determine the bacteriologic and clinical efficacy of antimicrobial therapy for nosocomial bacterial pneumonia selected based upon information provided by cultures of protected specimen brush (PSB) samples obtained during bronchoscopy, 76 consecutive patients with ventilator-associated pneumonia were studied using follow-up quantitative PSB cultures obtained after 3 days of treatment . Of the 173 microorganisms initially present in the PSB samples, only 11 (6%) were not eradicated by antimicrobial therapy, including three recovered at high (> or = 10(3) cfu/ml) concentrations . Thirty-two emerging pathogens, including nine at high concentrations, were also detected; 26 of them (81%) were resistant to the initial antibiotics administered . Of the 76 patients included in the study, cultures of follow-up PSB samples identified 51 in whom the infection site in the lung was completely sterilized, 16 with low-grade infection, and only nine with persistent high-grade infection . Analysis of clinical outcome within the 15 days after the initiation of antimicrobial therapy demonstrated clinical improvement in 62 of 67 (93%) patients in whom the site of infection was contained by treatment as compared with four of 9 (44%) patients with persistent high-grade infection (p < 0.01) . These data suggest that appropriate antimicrobial therapy for ventilator-associated pneumonia results in the control of the initial infection in 88% of the patients . However, an early superinfection caused by multiresistant pathogens can occur in a small subset of these patients . When follow-up PSB cultures were negative, an improved outcome was noted.

Arch Surg, 1993 Jan, 128(1), 79 - 88
Antimicrobial prophylaxis for surgical wounds . Guidelines for clinical care; Page CP et al.; Prophylactic administration of antibiotics can decrease postoperative morbidity, shorten hospitalization, and reduce the overall costs attributable to infections . Principles of prophylaxis include providing effective levels of antibiotics in the decisive interval, and, in most instances, limiting the course to intraoperative coverage only . Use in The National Research Council clean contaminated operations is appropriate and, in many instances, has been proven beneficial . Antibiotic prophylaxis is also indicated for clean operations, such as those involved with insertion of prosthetic devices, that are associated with low infection risk and high morbidity . Extension of antibiotic prophylaxis to other categories of clean wounds should be limited to patients with two or more risk factors established by criteria in the study of the efficacy of nosocomial infection control (SENIC) because the baseline infection rate in these patients is high enough to justify their use . Cefazolin (or cefoxitin when anaerobic coverage is necessary) remains the mainstay of prophylactic therapy . Selection of an alternate agent should be based on specific contraindications, local infection control surveillance data, and the results of clinical trials . Newer criteria for determining the risk of "site infection" (wound and intracavitary) are in evolution and may lead to modification of these recommendations over the next several years.

Tijdschr Diergeneeskd, 1993 Jan 1, 118(1), 8 - 10
{Possible effects on the environment of antibiotic residues in animal manure}; van Gool S; After application to animals veterinary drugs can enter the environment faeces . Little is known about the impact these veterinary drugs can have on the environment . Antimicrobial drugs, ended up in the soil via manure, could affect microorganisms and thus disturb ecological cycles . A study of the literature on the impact on the environment of a number of important (groups of) antibiotics and an antiparasitic agent revealed that little is known about most of these agents.

Chest, 1993 Jan, 103(1), 283 - 4
Candida endocarditis . A treatable form of pacemaker infection; Wilson HA Jr et al.; Fungal endocarditis is a rare complication of permanent pacemaker implantation . In all reports we have identified, this infection has been fatal, diagnosed postmortem . We present a patient in whom early echocardiographic diagnosis resulted in curative surgical and antimicrobial therapy . Fungal endocarditis is an unusual, but treatable complication of permanent pacemakers.

J Clin Lab Anal, 1993, 7(5), 263 - 8
Measurement of antimicrobial agents in cerebrospinal fluid using the Abbott TDx analyzer; Jandreski MA et al.; Occasionally, requests are made by our physicians for the measurement of gentamicin, tobramycin, or vancomycin in cerebrospinal fluid (CSF) specimens during the course of treating patients for bacterial meningitis . We evaluated CSF as a specimen type for the measurement of amikacin, gentamicin, tobramycin, and vancomycin on the Abbott TDx analyzer . Coefficients of variation for CSF spiked with these antimicrobial agents ranged from 0.8% to 6.5% for intra-assay values and from 2.1% to 2.3% for inter-assay values . Serum and CSF specimens were spiked at various levels with equal amounts of the antibiotics . Correlation coefficients for serum vs . CSF for these agents were 0.999 . Recoveries ranged from 86% to 134% . Sensitivity for these assays is about fourfold better for CSF than for serum . CSF appears to be an acceptable specimen type for the measurement of these antibiotics using the Abbott TDx analyzer.

Curr Opin Periodontol . 1993;:89-96.
Mouthrinses in the prevention and treatment of periodontal disease; Baker K; Although the ideal topical antimicrobial does not exist, some marketed products possess many of the desirable characteristics of such an agent . Antimicrobial agents from a number of different chemical categories are being evaluated continuously . Recent clinical trials evaluating the effectiveness of chlorhexidine, stannous fluoride, prebrushing rinses, phenolic compounds, cetylpyridinium chloride, and new agents such as triclosan are described . Other trials involving special patient groups such as the elderly, mentally handicapped, and orthodontic patients, are discussed . Recent articles on alternative roles for topical antimicrobials are also identified.

Curr Opin Periodontol . 1993;:71-7.
The current status and future prospects of altering the pathogenic microflora of periodontal disease; Chen C et al.; Modern periodontal therapy aims to suppress or eradicate periodontal pathogens and to maintain a posttreatment flora that is compatible with health . Systemic and local antimicrobial therapies have demonstrated effectiveness against several periodontal pathogens . Sustained-release devices, or irrigators, for local application of antimicrobial agents to periodontal pockets show great promise . Replacement therapy and periodontal vaccines, although still in the early research phase, represent very interesting approaches for preventing periodontitis . Using modern molecular genetic methods, it is theoretically possible to clone virulence determinants of periodontal pathogens into a nonpathogenic organism . The carrier organism with the expressed foreign antigens may be implanted in the oral cavity or the intestinal tract to induce long-lasting immunity against the targeted periodontal pathogens.

Curr Opin Periodontol . 1993;:43-51.
Periodontal considerations in the patient with HIV; Ryder MI; The HIV-associated periodontal diseases present unique challenges to the dental practitioner . The presence and severity of HIV-associated gingivitis, HIV-associated periodontitis, and possibly necrotizing ulcerative gingivostomatitis, and other oral lesions may indicate the presence and staging of HIV infection . In general, a similar relationship does not appear to exist between adult periodontitis and HIV staging . There is a wide variation in recent reports on the epidemiology of HIV-associated diseases . These variations point to the need for a standard definition for HIV-associated periodontal diseases using both conventional periodontal evaluation criteria and criteria designed specifically for the characteristics of HIV-associated gingivitis and HIV-associated periodontitis . HIV staging, geographic location of the study, antiviral and antimicrobial therapies, and oral habits may also account for many of these differences . Both the HIV-associated gingivitis and periodontitis lesions have similar microbiologic profiles to adult periodontitis lesions for previously identified periodontopathic bacteria . In addition, these lesions may have a unique opportunistic microflora . The pathogenesis of HIV-associated periodontal diseases may be due to the microflora, the effects of HIV and other viral agents, or alterations in the host response . These factors should be taken into consideration in the treatment and prevention of these HIV-associated periodontal lesions.

Pneumonol Alergol Pol, 1993, 61(7-8), 394 - 9
{Clinical analysis of ofloxacin in treatment of postinfectious exacerbations of endogenous bronchial asthma}; Frank-Piskorska A et al.; The aim of the study was to analyse the clinical effectiveness of ofloxacin in treatment of post-infectious exacerbations of endogenous bronchial asthma . Twenty eight patients (20 males, 8 females) were assessed . The following parameters were evaluated: bacteriological examination of the sputum (before and after treatment), morphological analysis of peripheral blood, bronchoalveolar lavage (performed in 11 patients) . Additionally in 7 patients lymphocyte subpopulations of the peripheral blood were determined (OKT4/OKT8) . Diurnal variations of serum levels of theophylline were assessed in 12 patients . The authors observed a clinical improvement in 26 patients . Following treatment the white cell blood count (WBC) and the CD4/CD8 ratio decreased . The same observations were made analysing the BAL differential count, in which a marked decrease of neutrophils was seen . The authors conclude that ofloxacin is a safe and efficient antimicrobial agent.

Eur J Cancer, 1993, 29A Suppl 3, S10 - 3
The effects of rhGM-CSF on macrophage function; Jones TC; Markers of monocyte/macrophage activity are numerous, and offer an insight on the potential effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) . These include anti-microbial effects, anti-tumour effects, inflammation and wound healing enhancing effects, antigen presenting effects and effects on the haematopoietic microenvironment . The actions of rhGM-CSF on monocytes/macrophages relevant to enhanced antimicrobial activity include increased phagocytosis, increased oxidative metabolism, increased numbers of Fc receptors, release of chemotactic factors and stimulation of mechanisms for killing intracellular viruses, fungi, bacteria and protozoa . Markers of macrophage anti-tumour activities can be divided into two types: those associated with antitumour antibodies, antibody-dependent cell cytotoxicity (ADCC) and those associated with synthesis and secretion of cytolytic substances by activated macrophages . In addition, rhGM-CSF has actions on fibroblasts and kerotinocytes consistent with an important role in wound healing . Moreover, the clinical use of rhGM-CSF to enhance antibody responses in conditions of inadequate immunisation is currently being investigated . Furthermore, rhGM-CSF appears to have a role in stimulating haemopoietic recovery following cytotoxic chemotherapy or radiation damage to bone marrow tissue.

Eur J Clin Microbiol Infect Dis, 1993, 12 Suppl 1, S27 - 30
The threat of multiresistant microorganisms; Vandenbroucke-Grauls CM; Enthusiasm about newly developed antimicrobial agents and disappointment because of the development of resistance have been alternating in the decades since the introduction of antibacterial chemotherapy around 1940 . During the last few years several mechanisms of bacterial resistance have been elucidated, and new insights into the genetic basis of multiresistance have been gained . The clinical implications of multiresistance depend on timely recognition of the problem, i.e . knowledge of the epidemiology of multiresistant microorganisms and the availability of alternative drugs . A particular problem arises from the fact that infections with multiresistant microorganisms often occur in the most critically ill patients.

J Pharm Biomed Anal, 1993 Jan, 11(1), 49 - 59
Characterization of the complexation of fluoroquinolone antimicrobials with metal ions by nuclear magnetic resonance spectroscopy; Riley CM et al.; The complexation of the fluoroquinolone antimicrobials is important because it has been implicated in reduced oral bioavailability and reduced antimicrobial activity when the drugs are co-administered with antacids or multi-vitamin preparations containing iron . The complexation of two model compounds, lomefloxacin and norflaxacin was studied using NMR . With aluminum ions, exchange between free and bound drug molecules was slow on the NMR time-scale . Two complexes, proposed to have stoichiometries of 2:1 and 3:1 (drug:metal) based on peak widths and variable temperature studies, were observed . The crystal structure of lomefloxacin, which shows intermolecular self association previously reported to be crucial to the drug's mode of action, is also reported . Because the metal ion complexes could not be crystallized, the crystal structure of uncomplexed lomefloxacin together with the NMR data on the aluminum complexes were used in the molecular modelling of the lomefloxacin-aluminum complexes.

APMIS, 1993 Jan, 101(1), 33 - 6
Susceptibility pattern of Scandinavian Francisella tularensis isolates with regard to oral and parenteral antimicrobial agents; Scheel O et al.; Some recently introduced antimicrobial agents have only been incompletely evaluated for use in Francisella tularensis infections . The present study evaluated the susceptibility pattern of Scandinavian human, rodent, and hare F . tularensis isolates with respect to a selection of traditional as well as recently introduced antimicrobial agents . All strains were resistant to the following beta-lactams: penicillin, cephalexin, cefuroxime, ceftazidime, aztreonam, imipenem, and meropenem with minimal inhibitory concentrations > 32 mg/l . Against macrolides, a mixed susceptibility/resistance pattern appeared . All strains were susceptible to gentamicin, chloramphenicol, doxycycline, and four quinolones . Since the quinolones showed the lowest MIC values, and in addition give a good intracellular penetration, we conclude that future drugs to consider against tularemia should definitely include this group of antibiotics . The outpatient mode of antibiotic treatment is especially relevant as the Scandinavian variant of F . tularensis infection is nonlethal, usually pustuloglandular, and not septicemic . Therefore, oral drugs must be sought, and the quinolone group also satisfies this requirement.

Antiviral Res, 1993 Jan, 20(1), 1 - 12
Efficacy of ganciclovir in combination with other antimicrobial agents against cytomegalovirus in vitro and in vivo; Freitas VR et al.; In MRC-5 cell cultures, the efficacy of the acyclic nucleoside ganciclovir (GCV) against human cytomegalovirus (CMV) was unaffected when combined with either amphotericin B (AMP B), ketoconazole (KCZ), dapsone (DAP), or trimethoprim/sulfamethoxazole (TMP/SMX) . When differences in 3-dimensional plots for antiviral activity and cytotoxicity of GCV alone and in combination were compared, the anti-CMV activity of GCV (IC50 8 microM, 5-9 microM range) was not affected by concentrations of up to 10 microM AMP B, 1000 microM KCZ, 100 microM DAP or 320 microM TMP/SMX (higher concentrations could not be tested due to cytotoxicity) . In Swiss Webster mice, the anti-CMV activity of GCV was also unaffected when administered in combination with any of the four other antimicrobial agents against murine CMV . GCV (s.c.) alone had an ED50 of 7 mg/kg (2-12 mg/kg range) which was unaffected by daily doses of 1 mg/kg AMP B (i.p.), 60 mg/kg KCZ (i.p.), 32 mg/kg DAP (p.o.) or 80/400 mg/kg TMP/SMX (p.o.) . These results suggest that GCV can be administered in combination with these other drugs for treatment of various opportunistic infections in AIDS patients without compromising the efficacy of GCV against CMV.

J Antimicrob Chemother, 1993 Jan, 31(1), 139 - 50
In-vitro activity of azithromycin on Chlamydia trachomatis infected, polarized human endometrial epithelial cells; Wyrick PB et al.; The in-vitro activity of azithromycin on Chlamydia trachomatis infected human endometrial epithelial cells, both primary and transformed cells growing in a polarized and non-polarized orientation, was analyzed . Addition of azithromycin two hours after adsorption inoculation with continued exposure until 72 h gave an MIC90 and MBC90 of 0.063 and 0.5 mg/L, respectively . In addition, the MBC results were more pronounced in infected cells growing in a polarized orientation . Numerous small fluorescent 'spots' (presumed small abnormal inclusions) were visible in the infected cells exposed to MIC concentrations of azithromycin . Immuno-transmission electron microscopy examination revealed intracellular inclusions filled with chlamydial envelope ghosts . Since standard diagnostic antigen detection methods use anti-envelope antibodies, the aberrant envelope-filled inclusions might be interpreted as viable inclusions by fluorescent microscopy and result in high false positive readings . To simulate treatment of an infected patient, azithromycin was added at 18 h to infected cells containing many reticulate bodies and exposure continued for 54 h after which killing of chlamydiae was seen . The use of polarized human cells may offer a more relevant in-vitro model system for examining the efficacy of antimicrobial action.

Chemotherapy, 1993, 39(1), 70 - 6
Enhancement of superoxide production of polymorphonuclear neutrophils by ofloxacin and the effects of the inhibitors of protein kinase C; Nagafuji T et al.; Polymorphonuclear neutrophils (PMN) represent an important defense mechanism against bacterial infection . Superoxide is one of the most important factors released by PMN following various stimulations including bacteria . Augmentation of chemiluminescence response of PMN stimulated by phorbol myristate acetate was observed following the addition of 25-200 micrograms/ml of ofloxacin, a new quinolone antimicrobial agent . In addition, the effects of two inhibitors of protein kinase C, staurosporine and H-7, were examined . The augmented superoxide production was inhibited by 1 or 2 microM of staurosporine or 50 or 100 microM of H-7 . These results suggest that ofloxacin augments superoxide production of PMN and that this augmentation is probably due to the enhancement of leukocyte protein kinase C.

Angiology, 1993 Jan, 44(1), 45 - 56
The damaging potential of leukocyte activation in the microcirculation; Schmid-Schonbein GW; Traditionally leukocytes have been regarded as beneficial cells, owing to their immunologic and antimicrobial activity . Recent evidence suggests, however, an additional role of granulocytes and monocytes as mediators of cardiovascular complications, such as ischemia, reperfusion, diabetes, physiologic shock, venous ulceration, and other conditions . Granulocytes and monocytes have a large volume, and stiff cytoplasm; they have the ability to adhere to endothelium and to other substrates; and they exert several forms of cytotoxicity . Granulocytes and monocytes may be trapped in the microcirculation, may obstruct capillaries and thereby induce a no-reflow phenomenon, and may initiate organ dysfunction via oxygen free radical production and proteolytic cleavage . Few organs seem to be spared from the potential destructive actions of these cells, and novel approaches are required to interfere with leukocyte accumulation in local regions of the peripheral circulation.

J Dent Res, 1993 Jan, 72(1), 25 - 30
The effects of triclosan and zinc citrate, alone and in combination, on a community of oral bacteria grown in vitro; Bradshaw DJ et al.; A mixed-culture chemostat system has been used as a more stringent laboratory system for evaluation of the antimicrobial effects of Triclosan and zinc citrate . The inhibitors were added alone, and in combination, as a pulse (a high initial inhibitor concentration which decreased with time) or as a dose (concentration of inhibitor increased with time) to give maximum concentrations of 34.5 mumol/L Triclosan and 39.8 mumol/L zinc citrate . When dosed, Triclosan inhibited A . viscosus and all five Gram-negative species, whereas zinc citrate had less effect, probably due to complexation by media components . Similar effects were seen when Triclosan was pulsed, except that S . mutans was the most sensitive Gram-positive species and V . dispar was unaffected . However, when the inhibitors were dosed or pulsed in combination, marked complementary and additive inhibitory effects were observed, particularly against Gram-negative species, although S . gordonii and S . oralis were relatively unaffected . The data confirm that increased effects can be obtained with suitable combinations of antimicrobial agents and suggest that, under certain conditions, apparently broad-spectrum antimicrobial agents may be acting more selectively than hitherto suspected.

Zentralbl Chir, 1993, 118(8), 482 - 91
{Intensive care medicine aspects of infection and septic multiple organ failure}; Bohrer H et al.; The clinical syndrome sepsis has been redefined recently, and the SIRS (systemic inflammatory response syndrome) concept has been developed . In the initial phase of sepsis, different mediator systems are activated finally resulting in a generalized endothelial inflammatory reaction . This reaction may lead to a vicious circle with subsequent multiple organ failure . Standard therapeutic regimen include the surgical removal of the source of sepsis, antimicrobial therapy, optimizing oxygenation, volume resuscitation, and treatment with catecholamines . Recently, new treatment modalities have become available . Replacement of antithrombin III, continuous venovenous hemofiltration, application of high doses of immunoglobulins and of low doses of hydrocortisone have been used . A monoclonal antibody against endotoxin (Centoxin) was taken from the German market in January 1993 . Experimental aspects of treatment include the administration of C1 esterase inhibitor, pharmacological inhibition of nitric oxide (NO), plasmapheresis, the application of non-steroidal anti-inflammatory agents and of high-dose naloxone as well as manipulation of cytokines.

Crit Rev Oral Biol Med, 1993, 4(3-4), 343 - 50
Sialochemistry: a diagnostic tool?
Aguirre A, Testa-Weintraub LA, Banderas JA, Haraszthy GG, Reddy MS, Levine MJ.
Saliva has proven to be a discriminating element in forensic arenas, an effective indicator of acute diseases of salivary glands, and a promising probe for drug monitoring . With the advent of sensitive immunochemical assays, the compositional profile of human salivary secretions has been expanded considerably . Thus, the establishment of a range of "normal values" for a variety of "intrinsic" and "extrinsic" salivary components represented the initial step to use saliva as a diagnostic tool of oral health status . Unfortunately, numerous cross-sectional studies have shown a wide individual variation in the salivary composition of healthy populations, thus precluding its use as a diagnostic chair-side test for the screening of the most common chronic oral diseases (e.g . caries and periodontal disease) . A possible explanation may arise from the wide functional versatility of salivary molecules . For instance, it has been recognized recently that in addition to its digestive properties, salivary amylase may modulate bacterial colonization, whereas histatins are not only antifungal but also bactericidal . Thus, low levels of already known antimicrobial salivary molecules (e.g., secretory IgA, lactoferrin, and lysozyme) could be compensated with higher concentrations of other molecules with antimicrobial activity, such as amylase and histatins . Consequently, for caries and periodontal diseases, longitudinal sialochemical studies may yield more insight than cross-sectional studies.

Crit Rev Oral Biol Med, 1993, 4(3-4), 251 - 9
Structural features of salivary function; Lamkin MS et al.; Saliva plays an important role in the maintenance of oral health by exhibiting multiple host defense functions . These include homeostatic processes, lubrication, antimicrobial activity, and the control of demineralization/remineralization of teeth . Biochemical studies of saliva and salivary secretions established that specific salivary proteins are responsible for these defense functions . Because some of these salivary proteins have been characterized extensively, including their primary structures, it has become feasible to explore their structure/function relationships . Acidic proline-rich proteins (PRPs), for example, exhibit high affinity to hydroxyapatite, inhibit crystal growth of calcium phosphate salts from solutions supersaturated with respect to hydroxyapatite, bind calcium ions, and interact with several oral bacteria on adsorption to hydroxyapatite . Statherins, histatins, and cystatins also exhibit affinities to mineral surfaces, inhibit calcium phosphate precipitation, and play a role in maintaining the integrity of teeth . Furthermore, histatins exhibit both antibacterial and antifungal activities . Approaches to identifying the functional domains of these salivary proteins include functional assays of enzymatically digested proteins and peptides, synthetic peptides and peptide analogues, and chemically modified proteins as well as biophysical studies of native proteins or peptides . Such studies have demonstrated that the fungicidal activities of histatins reside in the middle portion of the polypeptide chain, whereas the hydroxyapatite binding domains of PRPs and statherin reside in the phosphorylated amino-terminal regions . Identification of functional domains is vital in understanding the mechanisms of action and this information can be exploited in the development of therapeutic agents.

Eur J Haematol Suppl, 1993, 54, 18 - 24
Teicoplanin versus vancomycin in the empirical treatment of febrile neutropenic patients; Chow AW et al.; Gram-positive infections have become prevalent among neutropenic patients with cancer . A prospective, randomized, double-blind trial of teicoplanin, 6 mg/kg every 12 h for three doses then every 24 h, versus vancomycin hydrochloride, 15 mg/kg every 12 h, in the empirical treatment of febrile neutropenic patients was undertaken among 50 consecutive patients with haematological malignancy . The patients also received piperacillin sodium, 3 g every 4 h, and tobramycin sulphate, 1.5-2 mg/kg every 8 h . Both groups (25 teicoplanin and 25 vancomycin) were comparable in age, sex, renal function, underlying disease and concurrent therapy . Among 22 patients (44%) with culture-proven infection, Gram-positive organisms were isolated in 15 (9 with bacteraemia) and Gram-negative in 11 (4 with bacteraemia) . Mixed or polymicrobial infection occurred in 8 patients . Serum 1-h peak and trough levels at steady state were 41 +/- 15 and 12 +/- 3 mg/l for teicoplanin (at 14 +/- 4 days), and 40 +/- 10 and 8 +/- 5 mg/l for vancomycin (at 0.9 +/- 0.6 days) . Mean elimination half-life and apparent volume of distribution at steady state were 80.5 +/- 21.5 h and 1.4 +/- 0.8 l/kg for teicoplanin, and 5.6 +/- 1.8 h and 0.6 +/- 0.2 l/kg for vancomycin . Empirical antimicrobial therapy was successful in 23 teicoplanin and 21 vancomycin patients, respectively (p = 0.67; two-tailed Fisher's exact test) . Nephrotoxicity (serum creatinine > 110 mmol/l), however, was more common among vancomycin patients (10 versus 2; p = 0.02), while termination of treatment due to adverse effects was also more common among vancomycin patients (10 versus 2; p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Scand J Infect Dis, 1993, 25(3), 357 - 64
Management of indwelling central venous catheters in pediatric cancer patients with fever and neutropenia; Riikonen P et al.; This prospective study comprises 97 episodes of fever and neutropenia in children with cancer and central venous access . In 76% of episodes, patients had a Broviac-Hickman-like catheter, and in 24% a totally implanted venous access chamber system . The need for catheter removal during a febrile infection was 0.32/1000 catheter days, and the documented sepsis rate was 0.59/1000 catheter days . Our data indicate that 94% of episodes of fever and neutropenia in total, 78% of documented septicemias, and 97% of fevers of unknown origin were curable with broad-coverage antimicrobial therapy without removing the central venous line . Totally implanted chambers had a lower infection rate than catheters of Broviac-Hickman type.

Int J Periodontics Restorative Dent, 1993, 13(2), 150 - 71
Gingival response to subgingival placement of monolithic tetracycline-impregnated fibers: microscopic observations; Kazakos GM et al.; This study examines and characterizes the soft tissue wall of periodontal pockets after a 10-day in vivo exposure to monolithic tetracycline-impregnated fibers, with and without root planing . Four teeth from each of eight patients were randomly assigned to (1) nontreatment (controls), (2) treatment by root planing only, (3) treatment by tetracycline fiber only, or (4) treatment by scaling and root planing and tetracycline fibers . Ten days after initial therapy, all teeth were extracted with associated soft tissue pocket walls intact . Three specimens were obtained from each tooth for examination by scanning microscopy, energy dispersive spectroscopy, and light microscopy . Results indicated that use of tetracycline-impregnated fibers over a 10-day period did not adversely affect the epithelial lining and had no significant effect on the density or character of the inflammatory response present in adjacent soft tissue and confirmed the antimicrobial effects of the fibers.

Implant Dent, 1993 Spring, 2(1), 19 - 25
Chemotherapeutics in implant dentistry; Zablotsky MH; Adjunctive treatment with various chemotherapeutic regimens in implant dentistry are reviewed along with the indications for specific approaches . The use of systemic antibiotics, topical antimicrobials, and various mechanical modalities are discussed in relation to patient maintenance and the repair of ailing implants.

Vet Res, 1993, 24(3), 251 - 9
Actinomyces pyogenes: susceptibility of 103 clinical animal isolates to 22 antimicrobial agents; Guerin-Faublee V et al.; Actinomyces pyogenes induces suppurative diseases in ruminants and many other animal species . Most of the earlier antimicrobial susceptibility data has been obtained by disk diffusion techniques . Minimal inhibitory concentrations (MIC) of 22 antibiotics for 103 strains of A pyogenes of animal origin were determined by agar dilution test (Mueller-Hinton agar supplemented with 5% sheep blood) . All the strains were susceptible to penicillin G, amoxicillin, methicillin, cephalothin, cefoperazone, pristinamycin, kanamycin, gentamicin, spectinomycin, chloramphenicol, vancomycin, novobiocin and rifampin . Fifty-nine percent were resistant to streptomycin, 67% to tetracycline, doxycycline and minocycline, 12% to erythromycin, spiramycin and lincomycin . Most of the strains resistant to macrolides and lincosamides exhibited a constitutive MLS(B)-like phenotype . In the cultural conditions used, it was not possible to determine accurate MIC of fucidic acid and pefloxacin.

J Int Med Res, 1993 Jan-Feb, 21(1), 1 - 14
Drug resistance in bacteria: history, genetics and biochemistry; Mitsuhashi S; The significance of the discovery of prontosil in 1932 as the initiating step in the development of the modern era of antimicrobial chemotherapy is reviewed . The history of the discovery and the development of chemotherapeutic agents, from penicillin in 1929 to present-day antibiotics, are summarized . The various mechanisms by which bacteria are able to overcome the protective effects of these therapeutic agents (from the sulphonamides to the new fluoroquinolones) and develop resistance to them are discussed in detail . Attempts to elucidate the mechanisms by which resistance to chemotherapeutic agents develops are vital to the future of antimicrobial chemotherapy.

Oncol Res, 1993, 5(4-5), 165 - 71
Interconversion and stability of duocarmycins, a new family of antitumor antibiotics: correlation to their cytotoxic and antimicrobial activities in vitro; Ichimura M et al.; Stability and interconversion of duocarmycins were studied in relation to their cytotoxicities and antimicrobial activities . The compounds studied included duocarmycin A and SA, which have a spirocyclopropylhexadienone moiety, and four halogenated seco-compounds of duocarmycin A: duocarmycin B1, B2, C1 and C2, from which the cyclopropane ring structure is absent . Duocarmycins were potent cytotoxic compounds to cells . The cytotoxic activity seen on Balb 3T3/H-ras cells after 72 h drug exposure was in the following order (IC50 (nM): concentration for 50% growth inhibition); SA (0.05) > A (0.3) > B2 (1.5) > B1 (3.0) > C2 (20) > C1 (40) . Average minimum inhibitory concentrations (MICs) of duocarmycins against microorganisms showed essentially the same ranking order as that of cytotoxicity . There was a large difference between SA and A in their stability in aqueous solvents . For halogenated seco-compounds, a good correlation was found between their cytotoxicities in vitro and their conversion rate to duocarmycin A, suggesting that halogenated seco-compounds undergo closure to the spirocyclopropylhexadienone structure, the pertinent active form, in cells.

Prog Med Chem, 1993, 30, 57 - 88
Semi-synthetic derivatives of erythromycin; Kirst HA; Semi-synthetic derivatives of erythromycin have played an important role in antimicrobial chemotherapy . First generation derivatives such as 2'-esters and acid-addition salts significantly improved the chemical stability and oral bioavailability of erythromycin . A second generation of erythronolide-modified derivatives: roxithromycin, clarithromycin, azithromycin, dirithromycin and flurithromycin, have been synthesized and have exhibited significant improvements in pharmacokinetic and/or microbiological features . In addition, erythromycin itself has expanded its utility as an effective antibiotic against a variety of newly emerged pathogens . As a result of these developments, macrolide antibiotics have enjoyed a resurgence in clinical interest and use during the past half-dozen years, and semi-synthetic derivatives of erythromycin should continue to be important contributors to this macrolide renaissance . Despite these recent successes, other useful niches for macrolide antibiotics will remain unfilled . Consequently, the search for new semi-synthetic derivatives of erythromycin possessing even better antimicrobial properties should be pursued.

Postgrad Med J, 1993, 69 Suppl 3, S97 - 105
An appraisal of povidone-iodine and wound healing; Goldenheim PD; Infection is one of the most frequent complications of wound healing despite the use of antibiotics and modern sterile technique; it accounts for considerable patient morbidity, discomfort, and prolonged hospitalization, and it must be avoided to permit proper healing . For this purpose, topical antiseptics have been employed for several years . Among these povidone-iodine formulations (polyvinylpyrrolidone iodine; PVP-I; e.g., Betadine preparations), which consist of a water-soluble complex of elemental iodine and a synthetic polymer, have a broad antimicrobial spectrum, and have not been reported to develop bacterial resistance . Because some reports have suggested that PVP-I may interfere with wound healing, a critical review of studies concerning PVP-I and wound healing was undertaken, with emphasis placed on in vivo models that replicate, as closely as possible, human wound healing . Four forms of PVP-I were evaluated: PVP-I solution, PVP-I skin cleanser/surgical scrub, PVP-I ointment, and PVP-I cream . PVP-I solutions had virtually no deleterious effect on wound healing: application of 10% PVP-I solution to rat, guinea pig, rabbit, or pig wounds did not reduce wound tensile strength or delay re-epithelialization . In three human studies, no significant difference in healing was observed for 1%, 5% or 10% PVP-I solution except for a slight delay during the first 24 hours after the application of 5% PVP-I solution in one study; healing was normal by 72 hours . PVP-I skin cleansers/surgical scrubs contain ammonium nonoxynol-4-sulphate and lauramide DEA which, like all detergents, can cause tissue damage and delay healing . This was substantiated by a guinea pig study in which the detergent component but no the antiseptic produced these effects . In human trials, no damage occurred if cleansing of the wound with PVP-I skin cleansers/surgical scrubs was followed by saline irrigation . These results are consistent with recommendations for promptly rinsing the wound with water to remove the detergent if detergent-containing PVP-I preparations are used for wound care . PVP-I ointment (10%) delayed wound closure inn rats during the fourth through tenth days post-treatment; however, during the next two weeks, healing was accelerated, and by day 24, healing was equal to the controls . No delays occurred when pigs or rabbits were tested . In human wounds, no delays occurred in healing, even when gel-type occlusive dressings were added to the wounds; in fact, bandage-wearing time was shortened in those patients treated with PVP-I ointment . PVP-I cream (5%) was also studied in humans; the cream formulation appeared to decrease healing time . Based on these studies, it can be concluded that povidone-iodine preparations do not have a deleterious effect on wound healing.

Postgrad Med J, 1993, 69 Suppl 3, S93 - 6
Evaluation of povidone-iodine alcoholic solution for operative site disinfection; Arata T et al.; A clinical investigation of povidone-iodine alcoholic solution on disinfectant efficacy at the operative site was carried out in comparison with poloxamer-iodine alcoholic solution and povidone-iodine aqueous solution . Bacterial samples obtained by the cylinder scrub method from 10 cm2 of abdominal skin pre- and post-disinfection were filtered using a millipore membrane and cultured aerobically at 37 degrees C for 48 hours . The antimicrobial efficacy of each product was expressed as the logarithmic reduction value (reduction factor) in resident bacterial counts . Significantly higher reduction factors (RF) of the total resident bacteria were obtained with povidone-iodine ethanol solution (RF 2.02) than with povidone-iodine aqueous solution (RF 1.17) . No adverse reaction was observed with either preparation during the study period . It is concluded that povidone-iodine ethanol solution is a reasonable and effective antibacterial agent for pre-operative skin preparation.

Skin Pharmacol, 1993, 6(3), 208 - 14
Comparative study of the activity and lingering effect of topical antifungals; Pierard GE et al.; We present a combined method of culturing pathogenic dermatophytes and yeasts on human stratum corneum . Topical marketed antifungals are applied in vivo, and the stratum corneum is removed by cyanoacrylate skin surface strippings . After inoculation of the test organism, the extent of fungal growth is measured, indicating by comparison with controls the level of inhibitory effect of the antifungal . Other samples of stratum corneum collected at different time intervals after the arrest of antimicrobial treatment are used to evaluate the lingering effect of the drug . The combination of the data gained by these approaches close to the in vivo situation is used to introduce a classification of antifungals.

Recent Results Cancer Res, 1993, 132, 57 - 65
Approach to the patient with prolonged granulocytopenia; Pizzo PA; In most centers treating cancer patients, significant progress has been made in permitting patients to survive even prolonged courses of neutropenia . This has resulted from a better understanding of the epidemiology of infection and the points during the clinical course when they pose a risk for the patient with prolonged neutropenia . Considerable benefit has been derived from the availability of more potent broad-spectrum antimicrobial agents and from organized strategies for when they should be initiated, how and when they should be modified, and for how long they should be continued . The possibility that the duration of neutropenia might be attenuated in patients receiving chemotherapy now seems real with the ever-expanding repertoire of cytokines and other biologic agents that augment the hematopoietic and immune systems . Coupled with the use of peripheral stem cell reconstitution or the insertion of genes into hematopoietic stem cells that might render them resistant to the cytocidal effects of certain chemotherapeutic agents, it now seems possible to envision regimens that might alter the consequences of neutropenia as we have come to know them . It is likely, therefore, as additional experience is garnered and as chemotherapy regimens are devised, that the optimal approach to the management of the patient with prolonged neutropenia will include the rational use of antibiotics together with cytokines and other biologicals . Hopefully, such regimens will permit the delivery of chemotherapy in a manner that might enhance its tumoricidal activity and improve the outcome of patients with cancer.

Glas Srp Akad Nauka {Med}, 1993, (43), 271 - 5
{Therapy of Lyme disease}; Niksic S; Lyme borreliosis is manifested as a multisystemic disease, depending on the clinical picture and severity of the illness in acute, subacute and chronic form . The disease evolves in three stages . A choice of therapy, route of administration and duration of treatment depend on the stage of the disease . The treatment of Lyme disease requires the use of antibiotics . The current antimicrobial therapy is successfully performed with the following antibiotics from ICN GALENIKA assortment . Natural penicillins-PENCILLIN CRYSTALISATUM for i.v . administration; JUGOCILLIN for i.m . administration and BIMEPEN which is administered orally; Semi-synthetic penicillins-SINACILIN, tetracycline AMRACIN; Cephalosporins- the most important is LONGACEPH- the third generation cephalosporin) . The recommended current treatment of Lyme disease requires employment of up-to-date therapeutic approach.

Eur Urol, 1993, 24(3), 305 - 11; discussion 312
Antimicrobial prophylaxis in urologic surgery: does it give some benefit?
del Rio G, Dalet F, Chechile G.
Three types of antibiotic prophylactic regimens were evaluated versus a control without prophylaxis (group A: 3,912 cases) in urologic surgery . The antibiotic regimens were: group B = cefazolin 1 g/12 h/3 days (3,660 cases); group C = cefonicid 1 g/24 h/3 days (2,076 cases), and group D = cefonicid 1 g single dose (3,169 cases) . The parameters used were the comparison of the corresponding rates of postsurgical sepsis and operative wound infections . Numeric investigations for the validity of a retrospective study (unpaired data) were performed: homogenicity test, relative risk point estimate and confidence limits (95%), and etiological fraction point estimate and confidence limits (95%) . Chi-square for other purposes were performed . Endoscopic handling was considered homogeneous (same infective risk), while open surgery was heterogeneous (p < 0.001) . In order to avoid probable bias, a correction factor was used . Although in different degrees, prophylaxis significantly reduced the morbidity of surgical wound infections (p < 0.001; etiological fraction > 90%) . The differences (p < 0.01) between groups B and C/D were attributed to pharmacokinetic causes (short T 1/2 of cefazolin) . To obtain the maximum protective effect, the use of antibiotics with a T 1/2 of > 4 h is suggested . There was no resistant mutans in previously sensitive strains . However, a significant selection of intrinsically resistant strains was observed . Monodose offers at lest the same advantages as multiple-dose therapy . In addition, the monodose selected in a lesser proportion both the resistant strains (p < 0.001) and the number of microbial associations (p < 0.01).

Eur J Med, 1993 Jan, 2(1), 28 - 32
Mortality in pneumococcal meningitis: a multivariate analysis of prognostic factors; Hoen B et al.; OBJECTIVES: The mortality due to pneumococcal meningitis remains high, ranging from 15 to 60% . The purpose of this study was to analyze the prognosis of pneumococcal meningitis using a multivariate approach . The objectives were to select the most accurate initial mortality risk factors in pneumococcal meningitis and to determine an individual probability of death according to these prognostic factors . METHODS: The records of 105 consecutive cases of proven pneumococcal meningitis were retrospectively reviewed . The following parameters, recorded at presentation were considered for prognostic analysis: age, sex, duration of symptoms and antimicrobial chemotherapy before admission, underlying debilitating conditions, occurrence of seizures, pneumococcal bacteraemia or pneumonia, Glasgow coma scale score, Simplified Acute Physiological Score (SAPS), Cerebral Spinal Fluid (CSF) leucocyte count, CSF protein level, CSF glucose level and CSF/blood glucose ratio . Those parameters having a prognostic value after univariate logistic regression analysis were then entered into a multivariate stepwise logistic regression model . RESULTS: In multivariate analysis, a fatal outcome was best predicted by 4 variables . In descending order, these were the Glasgow coma scale score, age, CSF glucose level and concomitant pneumonia . The risk of dying was ten times higher in patients with Glasgow coma scale score < 7, seven times higher in patients older than 45 or having a CSF glucose level lower than 0.6 mmol/L and 4 times higher in patients with pneumonia . The logistic model provided an equation for the probability of dying that proved to have predictive values greater than 80% in determining the individual prognostic of pneumococcal meningitis . CONCLUSIONS: Our results are in agreement with most of previously published findings . We further demonstrated that the individual prognosis of pneumococcal meningitis could be accurately predicted with only 4 variables and highlighted the preeminent prognostic value of Glasgow coma scale score.

Surg Gynecol Obstet, 1993, 177 Suppl, 11 - 7; discussion 35-40
A critical analysis of recent innovations in the treatment of intra-abdominal infection; Wilson SE; Toward the end of the last decade, clinical trial results in the surgical literature reported a major improvement in survival from serious intra-abdominal infection . Mortality rates for certain complex infections, such as necrotizing pancreatitis and postoperative abscess, decreased by almost 50 percent when compared with both hospital controls and the predicted mortality rate according to severity of illness (1-3) . This remarkable improvement in outcome can be attributed to innovations in perioperative methods, image-guided therapy for management of postoperative abscesses and other complications and more effective antimicrobial therapy . Advances in each area, along with supporting data and the limitations of therapy, will be reviewed critically . Methods that have been proved by clinical trial will be emphasized.

J Med Virol, 1993, Suppl 1, 58 - 66
Sensitivity monitoring of clinical isolates of herpes simplex virus to acyclovir; Collins P et al.; Zovirax (acyclovir, ACV) is now widely accepted as a safe and effective treatment for the management of herpes simplex virus (HSV) infections in normal and immunocompromised patients . However, a common concern with regard to the widespread use of any antimicrobial agent is resistance . The virus specific mechanism of action of ACV involves two virus encoded enzymes, thymidine kinase (TK) and DNA polymerase . Any alteration in the genes coding for these two enzymes would therefore be expected to confer resistance . The findings from two extensive resistance monitoring programs have shown that in immunocompetent patients receiving ACV for the management of acute HSV disease, the incidence of resistance is extremely rare . The situation in the immunocompromised is different . In this patient group HSV disease is severe and protracted often requiring prolonged therapy thus increasing the exposure of the virus to drug . As a result HSV isolates resistant to ACV have occasionally been recovered . Biochemical and genetic analysis of the resistant clinical isolates has shown that resistance in the most part is due to an inability of the virus to produce TK which mirrors the findings with cell culture derived resistant virus . Laboratory studies would indicate that TK-deficient virus would have little clinical impact . Significantly, resistance has rarely been attributed to alterations in the substrate specificity of TK or DNA polymerase . The biological significance of these mutants is unclear but to date there has been no evidence of transmission of resistant virus.

Acta Orthop Belg, 1993, 59(3), 239 - 48
{Plaster of Paris: a carrier for antibiotics in the treatment of bone infections}; Mousset B et al.; Local antibiotherapy by diffusion from plaster of Paris is a promising method in orthopedic surgery . Nevertheless, the characteristics of this matrix have not yet been extensively studied with respect to regulation of drug-carrier capacity . From the careful comparative investigation of five commercialized plasters of Paris, it appears that the material must be constituted of fine homogeneous crystals devoid of any additive in order to obtain reproducible implants which are sufficiently hard . This condition determines their use as a biodegradable filler of bone cavities . Because of the antimicrobial spectrum, diffusion velocity and synergistic effect of sodium fusidate, amoxicillin trihydrate and sodium amoxicillin, this association of antibiotics with the plaster of Paris appears to be a useful sterilizing delivery system . The plaster of Paris allows a significant release of sodium amoxicillin during the first 3 days . This is followed by an important sustained liberation of sodium fusidate and amoxicillin trihydrate for one week . Finally, the local release of sodium fusidate for at least 2 weeks at concentrations higher than the minimum inhibition concentrations (MIC) of the most frequently infecting pathogens in osteomyelitis, will allow the sterilization of bone cavities.

Vet Hum Toxicol, 1993, 35 Suppl 2, 40 - 56
Consideration of sheep as a minor species: comparison of drug metabolism and disposition with other domestic ruminants; Short CR; The processes which determine bioequivalence of a given drug among species are many, and include absorption from a site of administration, renal, biliary and intestinal elimination, sequestration (in particular, binding to proteins or other macromolecules), distribution and redistribution, biotransformation, and receptor population density and uniqueness . The present review is limited to physiologic and pharmacologic parameters which affect drug distribution, elimination, and metabolism, primarily because these are areas where sufficient data is available to make comparisons between sheep and other ruminants . The literature suggest a high degree of similarity among domestic ruminants in the distribution and elimination of drugs that are not metabolized but eliminated by passive processes such as renal glomerular filtration . Although the data are not as uniform as when conducted under rigorous control in the same laboratory setting, it is possible to predict very similar pharmacokinetic profiles for many of the antimicrobials between cattle, sheep and goats . Metabolic scaling of kinetic parameters could be predicted in comparative studies conducted under well-controlled conditions, in which case the greatest similarities would occur among the small ruminants with values being somewhat dissimilar between sheep or goats and cattle . Plasma protein binding of drugs appears to be very similar among the ruminants, and its influence on drug distribution and elimination does not appear to vary appreciably between cattle and sheep . There is, however, very little definitive data which describes binding parameters, and there is very little data of any kind on binding to caprine albumin other plasma proteins of the goat . Sheep apparently differ from cattle, however, in transcortin concentrations, and this could affect the distribution and elimination of prednisolone or any other synthetic steroid which exhibits high affinity binding to this transport protein . Among the drug substances for which comparative information is available, there is very little to suggest qualitative differences in routes of metabolism among ruminants . There appears to be a remarkable degree of similarity in both major and minor pathways of drug metabolism among these species, and in fact, no documentable differences of a qualitative nature have been found . It should be noted, however, that documentable differences would only be established in a direct comparison of species conducted in the same laboratory under carefully controlled conditions . Such conditions would necessarily include assurance of no recent exposure to enzyme inducing agents or inhibitors or to agents which could deplete endogenous substances necessary to the enzymatic process.(ABSTRACT TRUNCATED AT 400 WORDS)

Vet Hum Toxicol, 1993, 35 Suppl 1, 6 - 9
European perspectives on the regulation of antimicrobial drugs; Kidd AR; EEC legislation has been drawn up over the past few years to harmonize requirements for authorizing and marketing veterinary medicines . These measures have taken into account not only antimicrobials used for treatment and prevention of disease but also those used for growth promotion . Existing Directives are in the process of amendment and in some instances the amended legislation has already been agreed upon . One of the issues dealt with in the original Directives was that of multiple antibiotic resistance, although only limited emphasis was placed on dealing with this aspect of microbiological concern . More recently, a Regulation has been issued which requires that an MRL (maximum residue level) should be set before Member States may grant marketing authorizations for any new product . A number of toxicological and pharmacological issues have to be addressed by the applicant in making up a dossier for determining the MRL, and the microbiological potential of residues is a subject which has to be considered . The applicant is given some degree of choice in determining precisely which studies to use to ascertain whether the induction or selection of resistant bacteria could alter the consumer's intestinal flora . This paper describes some of the background to the EC legislation on the studies required for residues and evaluates the need for such studies.

Schweiz Arch Tierheilkd, 1993, 135(10), 298 - 304
{The effect of pregnancy and lactation in sows on the pharmacokinetics of the gyrase inhibitor marbofloxacin}; Petracca K et al.; Six pregnant sows were treated in early pregnancy, late pregnancy and during lactation . Four empty sows served as control . 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) and microbiological assay . Pharmacokinetic parameters were calculated by use of a noncompartment model . 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 (5.74 h) than that of the early pregnancy group (10.09 h) . 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, the antibiotic dose should be increased during lactation.

Rev Med Chil, 1993 Jan, 121(1), 41 - 5
{Diagnosis of bacterial meningitis by latex agglutination tests}; Rodriguez G et al.; Fifty samples of cerebrospinal fluid (CSF) from patients with acute bacterial meningitis were studied with direct gram examination, culture and latex agglutination . Twenty one of these samples had previous antimicrobial treatment . In 42 patients, blood cultures were also made . Thirty control CSF samples were also studied . The diagnostic yield of CSF culture was 72%, of direct gram examination 74% and latex agglutination 80% . All the techniques as a whole has a diagnostic yield of 92% . In the 21 CSF samples with previous antimicrobial treatment, culture was positive in 47.6% and latex agglutination in 85.7% . All control CSF samples were negative . It is concluded that the diagnostic yield of latex agglutination test in patients with previous antimicrobial treatment is significantly better than culture.

Rev Argent Microbiol, 1993, 25(1), 27 - 35
{Diagnosis of entero-invasive Escherichia coli associated with diarrhea}; Chinen I et al.; Sixteen Escherichia coli strains isolated from diarrhea patients, characterized as enteroinvasive (EIEC) by the keratoconjunctivitis test (Sereny test), and 15 non-EIEC strains, were studied . The aim of this study was to establish a possible correlation between the Sereny test and several other tests as enzyme-linked immunosorbent assay (ELISA) and biochemical markers, which are more easily accessible to general practice laboratories . Strains were assayed for the virulence marker antigen (the outer membrane proteins) by direct ELISA, biochemical tests, antimicrobial susceptibility profile and serotyping . Mean optical density (OD) values in the ELISA were 2.018 +/- 0.336 for EIEC strains, and 0.569 +/- 0.283 for non-EIEC strains . Difference between the OD values of the two groups was found to be significant at p < 0.01 by the one-tailed Student's test . One (6.2%) of the 16 Sereny test-positive strains was negative by ELISA . Considered as a group, the EIEC strains are rather heterogeneous in their biochemical characteristics . Lysine decarboxylase test appeared as the most relevant assay, since all EIEC strains were negative for this enzyme, whereas 66.7% of non-EIEC strains were positive . Other helpful tests performed for strain characterization were: gas production from glucose and from glycerol, sucrose and salicin fermentation, and esculin hydrolysis (p < 0.01) . However, strains behaviour was variable with these tests . Differences between both groups of strains with regard to mucate utilization and dulcitol fermentation was significative only to a 5% level . Antibiotic sensitivity patterns showed differences between EIEC and non-EIEC strains: 37.5% of the former vs 80% of the latter, were resistant to at least four of the antibiotics tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Otolaryngol Chir Cervicofac, 1993, 110(6), 326 - 31
{Physiopathological and therapeutic values of experimental model of acute otitis media . Review of the literature}; Barry B et al.; The animal model of acute otitis media (AOM) has been widely used to study the pathophysiology and treatment of this disease . Different authors have demonstrated a both mechanic and immunologic role of concomitant viral infection in the pathogenesis of AOM . The specific immune response was found mainly local in otitis media due to S . pneumoniae and systemic with H . influenzae . Local and systemic complications are currently precise . This model was proved useful in pre-clinical evaluation of antimicrobial agents and development of vaccines.

Klin Khir, 1993, (11), 16 - 8
{The use of Kapromed A and Kaproiod sutures in surgery of the extrahepatic bile ducts}; Polous IuM et al.; The experimental substantiation and clinical approbation of the absorbable antimicrobial threads "Capromed A" and "Caproiod" in the surgery of the extrahepatic bile-ducts were carried out . The complications caused by the use of suture material were not revealed . A high effectiveness of the "Caproiod" thread in the emergency surgery of the extrahepatic bile ducts was noted.

Med Dosw Mikrobiol, 1993, 45(4), 477 - 81
{Helicobacter pylori in mucous membrane of stomach and duodenum of patients with symptoms of ulceration and dyspepsia}; Matras J et al.; The material consisted of samples of mucous membrane of stomach and duodenum obtained during endoscopy in patients with clinical symptoms of peptic ulcer of stomach or the duodenum or with dyspeptic problems . Samples were tested for presence of H . pylori by culture on brain-heart agar supplemented with 7% of horse blood . Direct test for urease production was also performed . Isolated strains were identified basing on morphology of growth, Gram-stained preparation, mobility of microorganism, production of oxidase, catalase and urease, and ability to agglutinate in immune goat serum for standard H . pylori strain . Out of tested 217 samples, positive result was obtained in 141 cases . Urease test was positive in 138 cases . Isolated strains were tested for susceptibility to 14 antimicrobials . They were all resistant to nalidixic acid and susceptible in 90-100% to cephalothin, furazolidone, gentamicin and ofloxacin.

Med Dosw Mikrobiol, 1993, 45(3), 339 - 43
{Drug resistance of Helicobacter pylori strains isolated from patients with inflammation of stomach mucous membrane and peptic ulcer of stomach and duodenum}; Borysiewicz J et al.; Twelve strains of H . pylori were tested . They were isolated from biosamples from 23 patients with stomach inflammation (16 persons) and stomach (3) and duodenum peptic ulcer . By application of solid medium dilution of MIC50 and MIC90-16 antibiotics and antimicrobials were tested . Values of MIC50 and MIC90 for antibiotics from the tetracycline group were, respectively 0.25-0.5 microgram/ml and 0.12-1.0 microgram/ml . Similar results were obtained with macrolide antibiotics . All strains were sensitive to penicillin (MIC 0.03-0.12 microgram/ml, ampicillin (MIC 0.06-0.5 microgram/ml) and amoxicillin and rifampicin (MIC 0.07-0.3 microgram/ml) . Ten out of 12 investigated strains were resistant to metronidazole (MIC90 = 30 micrograms/ml) . Results of this study may be important for etiotropic treatment of infections with H . pylori.

Braz Dent J, 1993, 4(1), 49 - 52
Antimicrobial action of AXOL on periodontopathic bacteria; Bretz WA et al.; The antimicrobial action of AXOL was tested against a panel of periodontopathic bacteria, which included Treponema denticola, Treponema vincentii, Treponema sp., Porphyromonas gingivalis, Prevotella intermedia, Prevotella melaninogenica, and Fusobacterium nucleatum . The AXOL commercial solution (undiluted) was effective in inhibiting some of the bacteria but not all . The rational for the use of antimicrobials is discussed.

Drugs Exp Clin Res, 1993, 19(5), 229 - 34
Antibiotic prophylaxis in cardiovascular surgery: a prospective randomized comparative trial of one day cefazolin versus single dose cefuroxime; Galbraith U et al.; With the intention of reducing prophylactic antibiotic dosage, previous studies in the Zurich University Hospital have shown that a one/day prophylactic antimicrobial regimen with cefazolin was as effective as a single dose of ceftriaxone . In this prospective randomized study one day cefazolin prophylaxis (1 g q 8 h i.v.) was compared with a single dose of cefuroxime prophylaxis (1.5 g) . In cases of cardiopulmonary bypass 0.75 g was added in the priming solution . In case of re-operation prophylaxis was repeated . 496 patients were enrolled in the study protocol; 78 patients were subsequently excluded . Of the remaining patients 224 (158 male, 66 female, mean age 61) were in the cefazolin group and 194 (142 male and 52 female, mean age 60) in the cefuroxime group . Mean duration of the intensive care unit (ICU) stay was three days in both groups and mean hospital stay was 16 days in the cefazolin group and 15 days in the cefuroxime group . The overall postoperative infection rate was 15.3%; 18.8% in the cefazolin group and 11.3% in the cefuroxime group . The statistical differences were found as in trend (p = 0.095) . The lower incidence of infectious complications in the single cefuroxime dose group may indicate an improvement in effectiveness of antimicrobial prophylaxis: it offers patients a reliable antimicrobial protection . In addition, the single dose prophylaxis has the advantage of easier handling, reduced dosage frequency and lower cost.

DNA Seq, 1993, 4(2), 123 - 8
Cloning and characterization of the guinea pig neutrophil cationic peptide-1 and -2 genes; Nagaoka I et al.; Guinea pig neutrophils contain the antimicrobial cationic peptides GNCP-1 and GNCP-2 in the granules . Using cDNA probes, four different GNCP gene clones were isolated from a guinea pig genomic library . Two clones encoded GNCP-1 and other two clones encoded GNCP-2 . The nucleotide sequence of GNCP-1 and GNCP-2 gene clones were highly homologous (> 97%) in the region sequenced . The GNCP-1 and GNCP-2 genes spanned 3 kb, and consisted of three exons and two introns . Exon 1 encoded the 5' untranslated region, exon 2 encoded the prepro-peptide region, and exon 3 encoded the mature peptide region and the 3' untranslated region . The transcription start site was located to a thymidine residue 93 bp upstream of the start codon (ATG) of GNCP-1 or GNCP-2 mRNA, and TATA-like sequence was located 24 to 30 bp upstream of the transcription start site . Glucocorticoid regulating element-like sequence was found in the 5' flanking region of the GNCP-1 or GNCP-2 gene, and the GNCP gene transcription rate of bone marrow cells was upregulated by dexamethasone treatment . Together these observations indicate that GNCP-1 and GNCP-2 are encoded by the very homologous but different genes, and that GNCP gene expression is regulated by glucocorticoid.

Arch Gynecol Obstet, 1993, 253(4), 193 - 6
The role of antibiotic prophylaxis for tubal microsurgery; Letterie GS et al.; OBJECTIVES . Antibiotic prophylaxis is effective in preventing postoperative wound infections and pelvic cellulitis for a variety of gynecologic procedures . Though frequently used, there is no uniform agreement and little data descriptive of the efficacy of antibiotic prophylaxis for infertility surgery . The purpose of the present study was to determine the incidence of postoperative infection-related complications after microsurgical tubal repair for infertility and to assess the possible role (if any) of antibiotic prophylaxis for tubal surgery . DESIGN . Retrospective; non-comparative; descriptive . MATERIALS AND METHODS . Three hundred and forty-eight tubal procedures were performed over a 3 1/2 year period and included tubal reanastomosis (n = 194), distal salpingostomy (n = 107), fimbrioplasty (n = 15), and tubal reimplantation and cornual isthmic anastomosis (n = 32) . All procedures were performed under general anesthesia using standard microsurgical techniques . No prophylactic antibiotics were given . When used, the operating microscope was not draped . Patients were monitored postoperatively for any infection-related complications to include postoperative febrile morbidity, wound infections, and pelvic cellulitis . A computer search of discharge diagnoses and chart review was made to determine the postoperative outcome and hospital course . RESULTS . There were 3 cases of febrile morbidity without localizing signs (0.8%), 3 wound infections (0.8%), 2 incisional seromas (0.5%), and one case of pelvic cellulitis (0.2%) . There were no cases of bacteremia, septic shock, or septic pelvic vein thrombophlebitis . All patients responded promptly to incisional drainage or combination antibiotic therapy . CONCLUSION . Data of the present study suggest that the incidence of infection-related complications after tubal surgery without antibiotic prophylaxis is very low . These data suggest that for tubal microsurgery where hemostasis is precise and tissue handling gentle, prophylactic antibiotics may not be necessary . Antimicrobials for prophylaxis, in these circumstances, may offer no advantage in reducing infectious complications that are already extremely low and may in fact cause unfavorable selective processes on endogenous flora and untoward side effects in selected individuals.

Folia Biol (Praha), 1993, 39(3), 162 - 5
Antimicrobial activity and immunological side effects of different antibiotics; Doric M et al.; Antibiotics, in addition to killing or inhibiting the growth of microorganisms, may also affect the immune response in many ways . Such effects may be clinically relevant especially when an impairment of immunological functions is seen . This study was designed to analyse the influence of various groups of antibiotics on the host defence system by using different tests in vitro on human or animal cells and in vivo on an animal model . At the same time we analysed the antimicrobial effectiveness of the same antibiotics on over 2800 bacterial strains isolated from our clinical material . Preliminary findings show that a correlation exists between the effect of antibiotics on the immune response, especially the humoral response, and the appearance of resistance in bacteria to these antibiotics.

Indian J Public Health, 1993 Jan-Mar, 37(1), 16 - 22
Drug consumption pattern in low socio-economic group in an urban community; Mitra J et al.; 117 families, having a total population of 558 were studied regarding drug consumption pattern . It was found that the average no . of episodes per person was 0.99 of which drugs were consumed for 72% of episodes . Significant difference was observed in consumption of drugs between males and females . Allopathic medicines were consumed for 93.3% of the episodes and the major source (53.8%) of medical care was from private practitioners . It was seen that the number of drugs consumed per episode of sickness rose as the per capita income increased . Vitamins and Minerals (22.3%) were the main group of drugs consumed . Drugs acting on the alimentary system (17.5%), Respiratory System (14.7%), Antimicrobials (14.6%) and Analgesics (10.8%) contributed to 80% of drug intake.

Trans Am Ophthalmol Soc, 1993, 91, 653 - 99
Antimicrobial pharmacokinetics in endophthalmitis treatment: studies of ceftazidime; Meredith TA; Ceftazidime has pharmacokinetic advantages for treatment of endophthalmitis caused by gram negative-organisms by intravenous administration . Additionally, its spectrum of coverage for these organisms and its relatively low toxicity after intraocular injection are favorable attributes . These studies demonstrate that inflammation leads to a significant reduction of the blood-ocular barriers to ceftazidime . This increased permeability shortens the half-life of the drug after intraocular injection but allows a significant penetration into the eye after a single intravenous dose so that therapeutic levels are achieved . Ceftazidime appears to be removed by both the anterior and the posterior route without active transport . The experiments demonstrate the importance of the vitreous as a barrier to achieving significant concentration of antibiotic within the eye after intravenous administration and confirm the importance of the vitreous in prolonging the half-life of drugs injected intravitreally . Finally the results emphasize that the pharmacokinetic behavior of drugs for treatment of endophthalmitis must be assessed in inflamed eyes both with and without intact vitreous, since these factors play a large role in drug availability and concentration in the vitreous cavity and are the major variables in the clinical setting.

Hematol Pathol, 1993, 7(4), 225 - 38
Expression of granule protein mRNAs in acute promyelocytic leukemia; Hirata RK et al.; The granule proteins are among the most abundant and characteristic proteins of myeloid cells . They are essential for the antimicrobial activity of these cells and they provide important markers for the differentiation stage of the myeloid series and for the diagnosis of myeloid leukemias . In acute promyelocytic leukemia (APL) there is high production of myeloperoxidase, and its cytochemical detection as well as the t(15;17) chromosomal translocation are important markers in the diagnosis of this acute myelogenous disease . The expression of other granule protein genes in APL has not been systematically determined . We have used the reverse transcriptase-polymerase chain reaction (RT-PCR) method to determine the pattern of expression of granule protein genes at the mRNA level in APL cells . We have examined the expression of the primary granule proteins defensin, myeloperoxidase, elastase, and cathepsin G; the secondary granule proteins lactoferrin, collagenase, and transcobalamin; as well as lysozyme, a protein reportedly found in both primary and secondary granules . mRNAs for all of these granule proteins were present in normal bone marrow mononuclear cells . We found that APL cells from three patients contain, in addition to myeloperoxidase mRNA, mRNAs for elastase, cathepsin G, and lysozyme . One patient had faint but detectable lactoferrin mRNA signal, but collagenase and transcobalamin mRNAs were not detectable in this patient . Defensin mRNA was found in one of the three APL patients, and all the primary granule protein mRNAs measured were found to be expressed in the APL cell line NB4 . None of the secondary granule protein mRNAs measured were detectable in NB4 cells . After treatment with retinoic acid (RA), which induces neutrophil maturation of these cells, weak induction of lactoferrin and collagenase but not transcobalamin was observed . However, in view of the weak transcobalamin signal observed in normal bone marrow, the absence of transcobalamin in RA-induced NB4 cells must be interpreted with caution . Interestingly, elastase and cathepsin G mRNA disappeared after RA induction, whereas defensin and myeloperoxidase mRNAs remained present . These findings indicate that granule protein mRNAs are regulated separately and differently, and that only minimal expression of secondary granule protein genes can occur in APL cells.

Am J Dis Child, 1993 Jan, 147(1), 30 - 4
Corticosteroids improve survival of children with AIDS and Pneumocystis carinii pneumonia; Sleasman JW et al.; OBJECTIVE--To determine if corticosteroids administered in addition to antimicrobials improve survival in children with acquired immunodeficiency syndrome and severe Pneumocystis carinii pneumonia (PCP) . DESIGN--Before-after, nonrandomized, case-comparison study . SETTING--Pediatric intensive care unit of a tertiary care teaching hospital in Florida . PARTICIPANTS--Eleven children infected with the human immunodeficiency virus (HIV) with confirmed PCP . SELECTION PROCEDURE--Infants with HIV infection and acute respiratory failure due to PCP were studied sequentially . INTERVENTION--The first seven infants were treated with antimicrobials alone while the next four received a 2-week course of methylprednisolone sodium succinate in addition to antimicrobials . MEASUREMENTS AND RESULTS--The two groups were similar with respect to age, route of HIV infection, stage of HIV disease, CD4 T-cell count, antiretroviral therapy, and respiratory parameters at intubation . All children treated with antimicrobials alone died while receiving mechanical ventilation . Survival of the children who received corticosteroid therapy was significantly improved (P < .05), and all were weaned from the ventilator . CONCLUSIONS--Corticosteroids administered in addition to antimicrobials and supportive care improve the short-term survival of HIV-infected children who have acute respiratory failure due to PCP.

Southeast Asian J Trop Med Public Health, 1993, 24 Suppl 1, 229 - 33
Disseminated intravascular coagulation in children: diagnosis, management and outcome; Chuansumrit A et al.; A retrospective study of 46 patients with disseminated intravascular coagulation (DIC) is reported . Twenty three patients were neonates with a mean age of 6.7 days (SD = 10) and twenty three patients had a mean age of 2.4 years (SD = 3.3) . The ratio of males to females was 1:1 . Thirty-two out of 46 patients (69.6%) had underlying diseases such as congenital abnormalities in cardiovascular and gastrointestinal systems . The diagnosis of DIC was suspected in the critically ill patients who had certain conditions that could trigger DIC . The laboratory findings revealed red blood cell fragmentation 93.4%, thrombocytopenia 95.5%, prolonged coagulogram 71.9% and increased FDP 74% . The management included treatment of underlying diseases, identification and relief of triggering conditions, correction of coagulopathy and supportive care . In terms of infection, appropriate antimicrobial agents were administered . Exchange transfusion was performed in 21 patients and heparin was given to patients with major vessel thrombosis such as renal vein thrombosis . Inspite of the above mentioned managements, the overall case-fatality rate was 52% . Factors related to high case-fatality rate were accompanying fatal diseases, shock, hemorrhage or thrombosis . There were no correlations between fatality rate and age, sex, triggered conditions or exchange transfusion . There is a need to establish an effective treatment that can stop the rapid ongoing process of DIC in order to achieve a better outcome in patients with DIC.

Drugs, 1993, 45 Suppl 3, 42 - 5
The use of quinolones in developing countries; Rodriguez-Noriega E et al.; The size of the antibiotic market in developing countries is double that seen in developed countries . There are some valid reasons for this difference, one of which is the higher frequency of diverse infections in the developing world . However, other factors are involved: for example, antibiotics are available without prescription, package insert information is poor, and there is no national antibiotic usage programme, all of which encourage inappropriate antibacterial use . When an antibiotic becomes widely prescribed by physicians, this is interpreted by the general public as meaning that the antibiotic is useful for all types of infections and the process of automedication begins . The newer quinolones, other new antibiotics, and indeed all antimicrobials should be available only by prescription . A package insert that includes all pertinent information should be provided, and each country should implement a comprehensive national antibiotic usage programme . Only through these measures will bacterial resistance be controlled and the effectiveness of each antibiotic class be maintained.

Drugs, 1993, 45 Suppl 3, 102 - 13
Fluoroquinolones and surgical prophylaxis; Dellamonica P et al.; The objective of surgical prophylaxis is to prevent wound infections associated with surgery . The rates of wound infections vary according to the procedure: less than 3 infections per 100 for clean procedures; up to 4 per 100 for clean-contaminated procedures; and up to 9 per 100 for contaminated procedures . Surgical antimicrobial prophylaxis has been shown in many randomised clinical trials to reduce the incidence of postoperative wound infections . Such prophylaxis is actually recommended in many clean-contaminated and some clean procedures . Because of their antimicrobial, pharmacokinetic, and antiadhesive properties, the fluoroquinolones have been recently proposed as prophylactic agents . Fluoroquinolones have proved to be useful in surgical prophylaxis and clinical trials have been performed in orthopaedic, cardiovascular, biliary, colorectal and urological surgery . According to the surgical procedure, fluoroquinolones were compared either with the standard antimicrobial regimen or with placebo . Different regimens of fluoroquinolones were also compared . Generally, fluoroquinolones have been demonstrated to be as effective as the reference prophylactic agent . In transurethral surgery, fewer postoperative wound infections were reported in the treated group than in the placebo group . In most studies, single dose prophylaxis was as effective as a multiple dose regimen . It is important to note that strict methodology was limited to a few clinical trials . In most of the studies, patients were not randomised in a double-blind fashion and small patient numbers often prevented the formation of satisfactory conclusions . Further trials are needed to define the role of the fluoroquinolones in surgical prophylaxis . It will be important to evaluate not only the efficacy but also the cost-benefit of perioperative prophylaxis with the fluoroquinolones . Clinical trials are also required in other high risk clean procedures such as neurosurgery involving shunts and ocular surgery . However, the risks related to the extensive use of fluoroquinolones in surgical prophylaxis must be considered, including the development and dissemination of resistant pathogens and the occurrence of adverse effects . In the future, surgical prophylaxis with prosthetic devices coated with fluoroquinolones should be considered.

J Calif Dent Assoc, 1993 Jan, 21(1), 55 - 69
Periodontal diseases in young individuals; Dougherty MA et al.; The prevalence and severity of periodontal diseases in young people are significant . Recent progress in understanding the etiology and pathogenesis of periodontal diseases in this group of patients has allowed significant improvement in periodontal classifications . Actinobacillus actinomycetemcomitans characteristically is the major pathogen involved; black-pigmented anaerobic rods and other organisms can also be important . Treatment of periodontitis should focus on meticulous plaque control and eradication of periodontal pathogens, possibly by means of systemic or topical antimicrobial therapies.

Ann Trop Paediatr, 1993, 13(1), 73 - 8
A community study of the application of WHO ARI management guidelines in Pakistan; Khan MA et al.; During a community-based study in four rural villages in Pakistan, 617 cases of acute respiratory infections (ARI) in children younger than 5 years of age were assessed, classified and managed according to the WHO ARI case management guidelines . Of these, 509 (82.5%) had 'cough and cold' without clinical evidence of pneumonia, 95 pneumonia, two severe pneumonia and 11 otitis media . Of the 509 without clinical evidence of pneumonia but with cough and cold, 491 (96.5%) were successfully treated without antibiotics and only 18 (3.5%) of these children needed antimicrobial therapy on follow-up . Of the 95 cases of pneumonia, 87 (91.4%) showed a satisfactory clinical response to oral cotrimoxazole and only eight (8.4%) required a change of antibiotic.

Drugs, 1993 Jan, 45(1), 15 - 28
Liposomes in drug delivery . Clinical, diagnostic and ophthalmic potential; Gregoriadis G et al.; Liposomes (phospholipid-based vesicles) have been investigated since 1970 as a system for the delivery or targeting of drugs to specific sites in the body . Because of their structural versatility in terms of size, composition, surface charge, bilayer fluidity and ability to incorporate almost any drug regardless of solubility, or to carry on their surface cell-specific ligands, liposomes have the potential to be tailored in a variety of ways to ensure the production of formulations that are optimal for clinical use . This includes controlled retention of entrapped drugs in the presence of biological fluids, controlled vesicle residence in the blood circulation or other compartments in the body, and enhanced vesicle uptake by target cells . Accumulated in vivo evidence, particularly in areas such as cancer chemotherapy, antimicrobial therapy, vaccines, diagnostic imaging and the treatment of ophthalmic disorders has indicated clearly that some liposome-entrapped drugs and vaccines exhibit superior pharmacological properties to those observed with conventional formulations . Such work has encouraged the application of liposomes in the treatment of diseases in humans . A large number of trials in patients with cancer or infections suggest that certain liposomal drug formulations are likely to prove clinically useful.

Drugs, 1993, 46 Suppl 1, 144 - 6
Controlled clinical studies of nimesulide in the treatment of urogenital inflammation; Lotti T et al.; Two double-blind, randomised studies were conducted to compare the efficacy and tolerability of nimesulide (200 mg/day) with those of placebo or bromeline (240 mg/day) . Treatments were administered orally to patients of either sex (aged 19 to 70 years) with acute infection and inflammation of the urogenital tract, and were given concomitantly with antimicrobial therapy for approximately 9 days . In both studies, a clinically significant improvement in symptoms, leading to complete remission, was achieved in most patients treated with nimesulide . Furthermore, treatment with nimesulide resulted in a more rapid improvement in symptoms and complete remission in a greater number of patients than did treatment with bromeline . Both nimesulide and bromeline were well tolerated.

N Engl J Med, 1992 Dec 17, 327(25), 1769 - 73
A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites; Shapiro ED et al.; BACKGROUND . Borrelia burgdorferi, which causes Lyme disease, is transmitted by deer ticks (lxodes dammini) in the northeastern and midwestern United States . Although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten . METHODS . To assess the risk of infection with B . burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite, we conducted a double-blind, placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic . Children and adults who had been bitten by deer ticks were randomly assigned to receive either amoxicillin or placebo for 10 days . Subjects were followed for one year for clinical manifestations of Lyme disease . Serum samples obtained at enrollment and six weeks and three months later were tested for antibodies against B . burgdorferi . RESULTS . Of the 387 subjects, 205 (53 percent) were assigned to receive amoxicillin and 182 (47 percent) to receive placebo . Of 344 deer ticks submitted and analyzed by the polymerase chain reaction, 15 percent were infected with B . burgdorferi . Erythema migrans developed in two subjects, both of whom had received placebo . There were no asymptomatic seroconversions and no late manifestations of Lyme disease . The risk of infection with B . burgdorferi in the placebo-treated subjects was 1.2 percent (95 percent confidence interval, 0.1 to 4.1 percent), which was not significantly different (P = 0.22) from the risk in the amoxicillin-treated subjects (0 percent; 95 percent confidence interval, 0 to 1.5 percent) . CONCLUSIONS . Even in an area in which Lyme disease is endemic, the risk of infection with B . burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated.

Biochemistry, 1992 Dec 22, 31(50), 12688 - 94
Design of model amphipathic peptides having potent antimicrobial activities; Blondelle SE et al.; Induced amphipathic alpha-helical conformations play an important role in the biological activity of peptides . By using reversed-phase high-performance liquid chromatography (RP-HPLC) as a means to study the secondary structure of peptides at aqueous/lipid interfaces, a sequence (Ac-LKLLKKLLKKLKKLLKKL-NH2) was found to readily adopt an amphipathic alpha-helical conformation upon interacting with the lipid groups of the stationary phase during RP-HPLC . This peptide exhibited potent antimicrobial activities against both Gram-positive and Gram-negative bacteria . We have prepared a complete set of omission, as well as of leucine and lysine substitution, analogs of this sequence . These analogs were used to investigate the effects of such alterations on the parent sequence's antimicrobial and hemolytic activities relative to each analog's behavior during RP-HPLC . The potential for the formation of ion channels through cell membranes by this amphipathic model peptide was also evaluated through preparation of analogs which varied in length from 8 to 22 residues, while maintaining their amphipathicity.

Biochem Biophys Res Commun, 1992 Dec 15, 189(2), 845 - 50
A novel anti-HIV synthetic peptide, T-22 ({Tyr5,12,Lys7}-polyphemusin II); Masuda M et al.; Tachyplesin and polyphemusin are antimicrobial peptides recently isolated from the hemocytes of horseshoe crabs (Tachypleus tridentatus and Limulus polyphemus) . We synthesized them and their analogs and examined their antiviral activity against human immunodeficiency virus (HIV) type 1 in vitro . The infection of human T cells with the virus was markedly inhibited by some of them at low concentrations . In this structure-activity study, we found that {Tyr5,12, Lys7}-polyphemusin II, which was designated as T22, had extremely high anti-HIV activity . Its 50% inhibitory concentration (EC50) was 0.008 micrograms/ml, while its 50% cytotoxic concentration (CC50) was 54 micrograms/ml and these values were comparable to those of AZT . This result indicates that T22 would be a potential candidate for the therapy of HIV infection.

Biochemistry, 1992 Dec 15, 31(49), 12416 - 23
Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes; Pouny Y et al.; Dermaseptin, a 34 amino-acid residue antimicrobial polypeptide {Mor, A., Nguyen, V . H., Delfour, A., Migliore-Samour, D., & Nicolas, P . (1991) Biochemistry 30, 8824-8830} was synthesized and selectively labeled at its N-terminal amino acid with either 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD), rhodamine, or fluorescein . The fluorescent emission spectra of the NBD-labeled dermaseptin displayed a blue-shift upon binding to small unilamellar vesicles (SUV), reflecting the relocation of the fluorescent probe to an environment of increased apolarity . Titrations of solutions containing NBD-labeled dermaseptin with SUV composed of zwitterionic or acidic phospholipids were used to generate binding isotherms, from which were derived surface partition constants of (0.66 +/- 0.06) x 10(4) M-1 and (2.8 +/- 0.3) x 10(4) M-1, respectively . The shape of the binding isotherms, as well as fluorescence energy transfer measurements, suggests that some aggregation of membrane-bound peptide monomers occurs in acidic but not in zwitterionic vesicles . The preferential susceptibility of the peptide to proteolysis when bound to zwitterionic but not to acidic SUV suggests that these aggregates might then penetrate a relatively short distance into the hydrophobic region of the acidic membrane . Furthermore, the results provide good correlation between the peptide's strong binding and its ability to permeate membranes composed of acidic phospholipids, as revealed by a dissipation of diffusion potential and a release of entrapped calcein from SUV.

Infect Dis Clin North Am, 1992 Dec, 6(4), 859 - 73
Infectious endophthalmitis; Pflugfelder SC et al.; The internist or family medicine consultant can have an important role in the management of endophthalmitis . Even though intraocular antimicrobial therapy is the most effective method of treatment, the consultant can assist in the selection of systemic antibiotic agents and in the monitoring of systemic side effects of the treatment . In addition, the consultant can be called on to evaluate patients with endogenous endophthalmitis for systemic involvement . The joint efforts of the ophthalmologist and consultant should allow optimal treatment in an attempt to improve the visual prognosis for these devastating ocular infections.

Pediatr Clin North Am, 1992 Dec, 39(6), 1259 - 76
The impact of respiratory infections on asthma; Cypcar D et al.; It is apparent that the effects of viral respiratory infections on the development of airway hyperresponsiveness are multiple and interrelated and involved the production of viral specific IgE, upregulation of leukocyte inflammatory activity, enhancement of the factors involved in the generation of late phase allergic responses, altered beta-adrenergic and cholinergic nervous system activity, and damage to the airway epithelium . The summation of these effects is the development of airway inflammation rather than a direct effect on bronchial smooth muscle, per se . An understanding of this pathogenesis underscores the relative importance of anti-inflammatory rather than antimicrobial therapy in viral-induced exacerbations in asthma symptoms.

J Med Chem, 1992 Dec 11, 35(25), 4745 - 50
Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity; Suto MJ et al.; Fluoroquinolones are potent inhibitors of bacterial topoisomerase II (DNA gyrase) . They can also inhibit eukaryotic topoisomerases, which could possibly lead to clastogenicity and/or cellular toxicity . Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the fluoroquinolones and the potential of these compounds to induce micronuclei, a genetic toxicity endpoint . In an effort to identify potent nontoxic quinolone antibacterials, we have examined the structural features of the fluoroquinolones associated with mammalian cell cytotoxicity . An investigation of a wide variety of substituents at the 1, 5, 7, and 8 positions of a quinolone nucleus was conducted . The results indicate that no one position has a controlling effect on the observed cytotoxicity . Instead, a combination of the various substituents contributes to the effects seen . Certain trends were apparent, such as the fact that compounds with pyrrolidines at the R-7 position were more cytotoxic than those with piperazines, and halogens at R-8 (X-position) were associated with more cytotoxicity relative to hydrogen . A general trend also existed between the cytotoxicity of the compounds and their Gram-positive antibacterial activity . A detailed comparison between the various groups and positional variations as they controlled the cytotoxicity and antibacterial activity is presented.

Clin Mater, 1993, 12(3), 169 - 79
Effect of addition of antimicrobial drugs to human collagen membrane; Al-Arrayed F et al.; Antimicrobial agents included in graft material for use in guided tissue regeneration of periodontally diseased tissue may be of value in combating infection, but may also alter the properties of the membrane material and exert an effect upon the host immune response . Metronidazole, niridazole and tinidazole were added to a cross-linked freeze-dried human type I collagen membrane in various doses and the following measured: (i) daily drug release into an aqueous solution, (ii) minimum inhibitory concentration (MIC) of the drugs against periodontopathogens, (iii) the effect of the drugs on mechanical properties of the membrane, and (iv) degradation by bacterial collagenase . In addition, the effects of the drugs on in-vitro cellular response was assessed by measuring blastogenesis of mononuclear cells obtained from patients suffering from periodontal disease and age/sex matched controls following incubation with the periodontopathogen Actinobacillus actinomycetemcomitans (AaY4) . It was found that the collagen membranes released high levels of the drugs, at concentrations well above the MIC values . The mechanical properties of the membranes were not affected by the addition of the drugs, although resistance to the collagenases were . The cellular immune response was likewise suppressed in both patient and controls at drug doses comparable with the in-vitro drug release patterns . It is concluded that incorporation of antimicrobial drugs in a collagen barrier membrane may be of value when used in guided tissue regeneration.

Biochemistry, 1992 Dec 8, 31(48), 12241 - 7
Conformation of tachyplesin I from Tachypleus tridentatus when interacting with lipid matrices; Park NG et al.; The mode of action of tachyplesin I, an antimicrobial cationic heptadecapeptide amide isolated from the hemocyte debris of a horseshoe crab, Tachypleus tridentatus, toward lipid matrices was studied with synthetic tachyplesin I, its analogs with Phe in place of Trp or Tyr, a linear analog with no disulfide bonds, and two linear short fragments . Circular dichroism spectra showed that tachyplesin I took an antiparallel beta-structure in buffer solution and a certain less ordered structure in acidic liposomes composed of egg phosphatidylcholine and egg phosphatidylglycerol (3:1) . Spectrophotometric titration of the peptides with laurylphosphorylcholine revealed that both Trp and Tyr residues orient toward the inside of lipid matrices, suggesting that they are on the same side of the peptide backbone . The carboxyfluorescein leakage experiment and fluorescence data indicated that tachyplesin I interacted strongly with neutral and acidic lipid bilayers and an aromaticity-rich hydrophobic part of the peptide was embedded in lipid membranes . All the peptides except for the short fragments were almost equally active in lipopolysaccharide binding . The energy-transfer experiment showed that a conformational change occurred such that the Tyr and Trp residues are positioned more closely to each other in acidic liposomes than in buffer solution . The present study strongly suggested that amphipathic lipid bilayers induced a conformational change of tachyplesin I from an energetically stable beta-structure to a less ordered, probably more amphipathic structure.

Immun Infekt, 1992 Dec, 20(6), 200 - 3
{New strategies for the prevention of foreign body infections}; Jansen B; Foreign body infections continue to present a challenge to modern medicine . New aspects for the prevention of such infections are presented on the basis of modifying medical devices or implant materials (synthetic polymers) . Physicochemical treatment of polymer surfaces is a possible tool to create anti-adhesive and thus anti-infective surfaces . Coupling or incorporation of antimicrobial substances to or into polymers is another way to prevent bacterial colonization and subsequently the development of polymer-associated infections.

Fam Pract, 1992 Dec, 9(4), 461 - 5
Short-lived effects of a formulary on anti-infective prescribing--the need for continuing peer review?
Wyatt TD, Reilly PM, Morrow NC, Passmore CM.
Because of the introduction of indicative drug budgets in the UK and their likely association with prescribing from a drug formulary, we have studied the effect of the introduction without continued reinforcement of a voluntary practice formulary on antimicrobial prescribing in a group practice . Detailed prescribing feedback for two matched periods before and after the launch of the Northern Ireland Faculty of the Royal College of General Practitioners practice formulary was compared . The parameters chosen were adherence to the formulary, generic prescribing and costs . A slight increase in prescriptions dispensed (3.5%) was observed between the two periods but prescribing costs increased by 32% . There was a 5.9% fall in the number of prescriptions for formulary agents following the launch of the formulary and a major increase (60%; P < 0.01) in the use of non-formulary antimicrobials particularly penicillins and tetracyclines . It was concluded that the high level of formulary prescribing prevalent during the production of the formulary was not maintained following its launch probably because of the lack of reinforcement.

Burns, 1992 Dec, 18(6), 479 - 85
Cytotoxicity evaluation of antiseptics and antibiotics on cultured human fibroblasts and keratinocytes; Damour O et al.; Infection is the greatest problem in burn patients and topical antimicrobial agents must be chosen with great care, especially when cultured skin is grafted . We examined the cytotoxic effect of six antiseptics and six antibiotics commonly used on cultured human fibroblasts and keratinocytes . Cultured cells were exposed for 15 min to Hibitane (chlorhexidine), Biseptine (chlorhexidine+benzalkonium chloride+benzylic alcohol), Benzalkonium Chloride, Yellow Betadine (polyvidone-iodine+nonoxinol), Betadine Scrub (polyvidone-iodine+quaternary ammonium) and Green Betadine (polyvidone-iodine) and viability was determined using the MTT test . At therapeutic concentrations all the antiseptics are cytotoxic for fibroblasts and keratinocytes . Additionally the cells were exposed for 48 h to vancomycin, colistin, amikacin, imipeneme, pefloxaxin, piperacillin and cell viability was determined using the MTT test . The concentrations of antibiotics corresponding to the plasma peak obtained after therapeutic application were not cytotoxic to the tested cells . The CD50 was much higher than the MIC (from 125 to 875 times for keratinocytes and from 1400 to 5900 times for fibroblasts) . These data suggest that commonly applied antiseptics must not be used before grafting cultured skin grafts . After grafting any infection can be controlled with topical applications of appropriate antibiotics.

J Vet Pharmacol Ther, 1992 Dec, 15(4), 364 - 78
Evaluation of antibiotics for racing pigeons (Columba livia var . domestica) available in The Netherlands; Zwijnenberg RJ et al.; Antibiotics and chemotherapeutics marketed for use in racing pigeons (Columba livia var . domestica) were evaluated by comparing the dosages and indications given by the manufacturers with the data obtained by pharmacokinetic, bacteriological and efficacy studies . This comparison showed that only three of the recommended dosages and indications of the 60 formulations marketed in The Netherlands are scientifically sound and in accordance with the literature . It is to be expected that the majority of the antimicrobials for pigeons will not satisfy the requirements for final registration as a pigeon therapeutic under the Dutch Veterinary Medicines Act of 1985 . Several factors affecting drug availability are discussed, such as the different routes of administration and the influence of food . The public health aspects of the consumption of medicated pigeons is also discussed . Although there is no legislation with regard to this subject, a recommended withdrawal time of 10 days for the majority of the antimicrobials seems advisable.

J Clin Pharmacol, 1992 Dec, 32(12), 1083 - 8
Pharmacotherapy and pharmacodynamics in the management of bacterial infection; Rotschafer JC et al.; Minimum inhibitory concentration testing is the most common standard used to evaluate antibacterial activity of antimicrobials against specific pathogens . The consideration of pharmacodynamic factors in conjunction with these tests can improve the management of bacterial infections . Further, the incorporation of MIC values into pharmacodynamic ratios may provide clinically useful tools for selecting optimal antibiotic selection, determining proper dosing strategies, and predicting therapeutic outcomes . Physiologic consequences of infection and antibiotic treatment, such as endotoxin release and initiation of the septic cascade, also must be considered when choosing appropriate anti-infective therapy . The introduction of adjuvant immunotherapy, along with improvement, validation, and implementation of pharmacodynamic predictors of antibiotic efficacy, undoubtedly will provide the medical community with an effective arsenal to further reduce the morbidity and mortality rates associated with bacterial infections.

An Med Interna, 1992 Dec, 9(12), 610 - 2
{Q fever and endocarditis . Apropos a new case}; Martinez-Albaladejo M et al.; Endocarditis is the first manifestation of Q fever in its chronic form, generally affecting prosthetic cardiac valves or previously injured valves . Its clinical presentation is an endocarditis with negative culture and there is not agreement with regard to the most adequate antimicrobial treatment and its duration . Frequently, the valve has to be replaced . We present a case of a patient with double aortic lesion, in whom endocarditis by Q fever was diagnosed and treated with doxycycline, initially with success . However, she relapsed one year later, being then resistant to the medical treatment (doxycycline, ciprofloxacine plus rifampicine) . It was not possible to replace the valve and the patient died two months later due to cardiac failure.

Rozhl Chir, 1992 Dec, 71(12), 663 - 70
{Intensive care in patients with intra-abdominal septic complications}; Vyhnanek F et al.; The authors investigated diagnostic and therapeutic possibilities of intensive care units when treating septic conditions in intraabdominal surgery . The authors emphasize the comprehensive and systematic character of the follow up of patients who are threatened by sepsis . Care involves in particular aimed antimicrobial therapy, immunotherapy, normalization of haemodynamics and the acid-base balance and rational parenteral nutrition . Only a thus conceived therapeutic regime makes it possible to control such serious conditions as sepsis.

Nippon Yakurigaku Zasshi, 1992 Dec, 100(6), 475 - 83
{Establishment of a method to analyze drugs in the hair and its application for determining patient compliance}; Uematsu T; The human scalp hair is a useful tissue that retains the past dosage history over a rather long period of time, acting like a "tape-recorder" . It should be emphasized that the sampling of hair can be made noninvasively by cutting a few to several pieces of hair nearest to the scalp . Because the hair continues to grow at the rate of about 1 cm/month, each 1-cm hair length contains the drug corresponding to the amount ingested over a 1-month period when the hair is cut into 1-cm lengths successively from the scalp end . However, the hair growth rate is variable both within and between individuals, and the hair has its own growth cycle, i.e., 2 to 8 years or more of the growing stage and a few months of the resting stage . Therefore, the validity of the obtained results must always be considered cautiously, especially in relation to whether a resting phase hair might have been sampled . For obtaining information on the growth rate and stage of a hair, a drug that can be detected in the hair even after a short-term exposure to the drug has been found . These drugs are antimicrobial quinolones such as ofloxacin . By analyzing the axial distribution of ofloxacin along the hair shaft, we can expect to determine the so-called "tape-speed" and "uniformity of tape-running" of a single hair.

Ann Pharmacother, 1992 Dec, 26(12), 1503 - 7
Outcomes of cefazolin versus ceftriaxone therapy in treating lower respiratory tract infections in adults; Thompson D et al.; OBJECTIVE: To determine whether choice of a first- versus third-generation cephalosporin as initial therapy for lower respiratory tract infections in hospitalized adults affects the course and duration of care, both of which may influence antimicrobial treatment cost . DESIGN: Retrospective analysis of discharge abstracts and hospital pharmacy records . SETTING: Forty-eight US acute-care hospitals . PATIENTS: One thousand ninety-two hospitalized adults (aged > 17 y) with principal diagnoses of lower respiratory tract infections (DRGs 79-80, 89-90) . INTERVENTIONS: Cefazolin or ceftriaxone, given as sole antimicrobial therapy for at least one day . MAIN OUTCOME MEASURES: (1) The number of patients who received another parenteral antibiotic anytime prior to hospital discharge; (2) the number of days during which patients received any parenteral antibiotic while in the hospital; and (3) the number of days patients remained hospitalized following the start of antibiotic therapy . RESULTS: Patients treated with cefazolin (n = 763) were more likely to receive another parenteral antibiotic while in the hospital (30.3 vs . 20.7 percent; p < 0.001) and received more total days of therapy (7.2 vs . 6.7 d; p < 0.05) than those treated with ceftriaxone (n = 329) . Although the time to hospital discharge did not differ in the full sample (9.2 d for both groups), it was greater among those receiving cefazolin (8.6 vs . 8.0 d; p < 0.05) when patients with lengths of stay exceeding 24 days were excluded from both groups . CONCLUSIONS: In addition to acquisition cost, differences in course and duration of care should be considered when determining the most cost-effective choice for antimicrobial therapy.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2634 - 8
In vitro susceptibilities of Actinobacillus actinomycetemcomitans to a number of antimicrobial combinations; Pavicic MJ et al.; The in vitro susceptibilities of Actinobacillus actinomycetemcomitans to 14 antimicrobial combinations were studied by using the checkerboard titration technique . The results, expressed as the range of the fractional inhibitory concentration indices, were as follows: for metronidazole or its hydroxymetabolite combined with cefixime, 0.2 to 0.6; for moxalactam, 0.2 to 0.6; for penicillin G, 0.3 to 0.6; for tobramycin, 0.8 to 2.0; for erythromycin, 0.8 to 1.7; for ciprofloxacin, 0.2 to 0.6; for tetracycline, 0.8 to 1.2 . Our observations indicated that the beta-lactam antibiotics as well as ciprofloxacin act synergistically with both metronidazole and its hydroxymetabolite against A . actinomycetemcomitans . Synergistic interactions were independent of the individual MICs of the antibiotics tested . Erythromycin, tobramycin, and tetracycline combined with either metronidazole or its hydroxymetabolite showed additive to indifferent effects against the five strains of A . actinomycetemcomitans, with the fractional inhibitory concentration indices ranging from 0.8 to 2.0 . A . actinomycetemcomitans was found to be highly susceptible to ciprofloxacin (MIC of ciprofloxacin for 90% of strains tested, 0.010 micrograms/ml) and cefixime (MIC of cefixime for 90% of strains tested, 0.8 micrograms/ml) . The results indicate that in patients who are allergic to penicillin, cefixime and ciprofloxacin may be useful alternative antibiotics in combination with metronidazole for the treatment of A . actinomycetemcomitans-associated periodontitis.

J Inorg Biochem, 1992 Dec, 48(4), 251 - 70
Synthesis, structure, antimicrobial, and genotoxic activities of organotin compounds with 2,6-diacetylpyridine nicotinoyl- and isonicotinoylhydrazones; Mazza P et al.; A series of organotin compounds obtained from the reaction of 2,6-diacetylpyridine nicotinoyl- and isonicotinoylhydrazones with tri- and diorganotin chlorides was investigated . The IR and 119Sn NMR spectroscopic characterization of all the compounds is reported, together with the x-ray crystal structure of {SnEt2(H2dapin')}2{SnEt2Cl3}Cl3.2H2O (H2dapin' = 2,6-diacetylpyridine bis(isonicotinoylhydrazone)) . The main feature in this compound is the presence of a tin atom in both the complex ionic units . The coordination polyhedron is a pentagonal bipyramid in the cation and a trigonal bipyramid in the anion . Results are discussed concerning the in vitro evaluation of antimicrobial properties and genotoxic potential of the compounds described . In all cases the complexes show a reduced antimicrobial activity as compared to that of the corresponding organotin compound . Genotoxic properties of the ligands, detected in the Ames test, disappear in the complexes.

Clin Chest Med, 1992 Dec, 13(4), 709 - 22
Sepsis in pregnancy; Fein AM et al.; Sepsis remains an uncommon, but potentially devastating problem in the previously healthy pregnant patient . Although septic sequelae, including organ failure and shock, are unusual, they are likely to lead to morbidity and mortality as high, or higher, than in the general population . At the present time, hemodynamic support, surgery, and antimicrobial therapy aimed at reducing polymicrobial aerobic and anaerobic infection remain the gold standard of therapy . New antimediator and anti-inflammatory therapies offer promise of improved survival in the general and obstetric population with severe sepsis.

Clin Chest Med, 1992 Dec, 13(4), 679 - 91
Pneumonia complicating pregnancy; Rodrigues J et al.; Although pregnancy is infrequently complicated by pneumonia, lung infection by bacteria, viruses, and fungi can pose serious maternal and fetal hazards . Pneumonia may lead to preterm labor and certain infecting agents, most notably the HIV virus, can cross the placenta and lead to neonatal infection . There is some evidence that the incidence of pneumonia in pregnancy may be increasing among certain populations . In addition, infections caused by viruses (varicella and influenza) and fungal agents, ordinarily controlled by cell-mediated immunity, may be more virulent to pregnant women, thereby adding to maternal mortality . Beyond the influence of these pregnancy-induced changes in immunity, there are certain physiologic changes in pregnancy that make it more difficult for the pregnant woman to sustain any type of respiratory infectious insult . Certain types of pneumonias, particularly influenza and aspiration, may be avoided if patients at risk are identified and existing strategies for prevention are applied . When the pregnant women is treated for lung infection, the safety of antimicrobial agents must be considered, and therapy may differ from that used in the nonpregnant patient.

Appl Environ Microbiol, 1992 Dec, 58(12), 3834 - 6
Electrochemical Ag+ for preservative use; Simonetti N et al.; In contact experiments with different experimental conditions, electrochemical Ag+ solutions exhibited better antimicrobial effectiveness against bacteria, a yeast species, and a mold than did analogous silver solutions from inorganic salts . The particular characteristics of electrochemical Ag+, such as the mode of action, effectiveness at low concentrations, and stability, indicate that Ag+ could be used effectively in preservatives.

J Pharmacol Exp Ther, 1992 Dec, 263(3), 1140 - 6
Cerebrospinal fluid transport and disposition of the quinolones ciprofloxacin and pefloxacin in rats; Jaehde U et al.; The disposition of ciprofloxacin and pefloxacin in the rat cerebrospinal fluid (CSF) was investigated after i.v . and i.c.v . administration . After injection into the lateral ventricle, the terminal half-life of pefloxacin was shorter than that of ciprofloxacin . After i.v . infusions, the relative CSF exposure, expressed as CSF: area under the plasma concentration time curve ratio, were found to be 10.4 +/- 2.8% for ciprofloxacin and 42.4 +/- 3.0% for pefloxacin . The unit impulse response methodology was applied in order to assess the CSF transport profile . The plasma-CSF transport clearance of pefloxacin and the total amount of drug transported into the CSF were significantly higher compared with ciprofloxacin . Although pefloxacin exhibited a linear CSF transport profile, the plasma-CSF transport clearance of ciprofloxacin was found to be nonlinear at the dose level studied . Pefloxacin was converted in the brain to the active metabolite norfloxacin (N-desmethyl pefloxacin) . The difference in CSF exposure of both quinolones and the presence of active metabolites of N-methylated quinolones in the CSF may be of clinical relevance in the treatment of CNS infections, but differences in antimicrobial activity have to be taken into account as well.

Semin Oncol, 1992 Dec, 19(6), 707 - 19
Antifolates: the next generation; Fleming GF et al.; A number of promising new antifolates have been entered in clinical trials in recent years . These agents have been rationally designed based on the current understanding of folate transport and metabolism and of the mechanisms by which cells become resistant to methotrexate . Methotrexate-resistant cell lines are generally sensitive to one or more of the newer antifolates, which differ from methotrexate by being either more lipid soluble, more extensively polyglutamated, or by inhibiting folate-requiring enzymes other than dihydrofolate reductase . Five of the agents furthest along in clinical testing, trimetrexate, piritrexim, edatrexate, lometrexol, and D1694, are discussed . These drugs offer exciting opportunities to expand the role of antifolates in cancer chemotherapy, as well as in antimicrobial and antirheumatic therapy.

Infect Dis Clin North Am, 1992 Dec, 6(4), 851 - 7
Fungal keratitis; Foster CS; As Jones has emphasized, the successful management of microbial keratitis, fungal or otherwise, necessitates five steps: (1) clinical suspicion and clinical diagnosis; (2) performing the proper laboratory procedures; (3) initiating antimicrobial therapy based on the results of laboratory studies; (4) modifying the initial therapy based on the clinical response; and (5) deciding correctly when and how to terminate therapy . Keratomycosis poses special diagnostic and therapeutic challenges for ophthalmologists because of its low incidence, and its resistance to treatment, because of the lack of antifungal agents with good penetration into the eye, and because of the difficulties in obtaining meaningful in vitro drug susceptibility results for fungal isolates . We believe, however, that ophthalmologists are now diagnosing keratomycosis earlier and treating it more effectively.

Infect Dis Clin North Am, 1992 Dec, 6(4), 807 - 13
Conjunctivitis of the newborn; de Toledo AR et al.; Infectious conjunctivitis of the newborn is caused by a wide variety of microorganisms . The ocular findings may be part of a widespread systemic infection . Clinical presentations are not diagnostic of the cause, and a microbiologic work-up with cytology, cultures, and microbial sensitivities is mandatory . The selection of specific antimicrobial therapy is based on the findings of laboratory studies . Prophylaxis with silver nitrate solution, 1.0% tetracycline, or 0.05% erythromycin ointment is effective for the prevention of gonococcal and chlamydial conjunctivitis in the newborn.

Clin Infect Dis, 1992 Dec, 15(6), 983 - 90
Persistent fever in association with infective endocarditis; Blumberg EA et al.; Fever persisting despite adequate antimicrobial therapy for endocarditis can be an ominous sign . To evaluate the significance of persistent fever in this situation, we reviewed the records of patients at three hospital affiliates of Albert Einstein College of Medicine . Twenty-six patients with 27 episodes of endocarditis and fever lasting for > or = 2 weeks despite appropriate antimicrobial therapy were identified and compared with a matched cohort of 26 patients with endocarditis but without prolonged fever . The median duration of fever in the former group was 35 days . Cardiac infection caused fever in 13 of these patients, seven of whom had myocardial abscesses . Additional causes of infection included drug treatment, nosocomial transmission of pathogens, and pulmonary emboli . Sixteen patients required cardiac surgery (seven on an emergent basis), whereas only two controls underwent such a procedure (P < .001) . Twenty-two patients with persistent fever and five controls developed nosocomial complications (P < .001) . Six patients with fever died, five from endocarditis-related complications . Thus persistent fever often indicates complicated endocarditis . We present an approach for the evaluation of the patients affected by this condition.

J Dent, 1992 Dec, 20(6), 375 - 6
Selection of dental procedures for antibiotic prophylaxis against infective endocarditis; Tan SY et al.; A dental source of infection remains the most common identifiable risk factor in infective endocarditis and this may be particularly important in patients at 'high risk' . We therefore performed a questionnaire survey of dental practitioners to assess acceptance of The British Society of Antimicrobial Chemotherapy (BSAC) recommendations, especially with regards to selection of dental procedures for antibiotic prophylaxis . The results showed that the dental practitioners surveyed treated the 'high risk' patient group differently by extending the range of dental procedures covered by antibiotics but the BSAC only recommend that they be treated differently by hospital treatment and/or parenteral antibiotics . This must be an area of concern and deserves further attention, especially with regards to the need for wider publicity and the range of dental procedures that should be covered in the 'high risk' group where morbidity and mortality from infective endocarditis are higher.

J Clin Microbiol, 1992 Dec, 30(12), 3230 - 3
Evaluation of a commercially available complement fixation test for diagnosis of Helicobacter pylori infection and for follow-up after antimicrobial therapy; Goossens H et al.; Commercially available complement fixation test reagents (Institute Virion Ltd., Ruschlikon, Zurich, Switzerland) available in package format were evaluated for the serodiagnosis of Helicobacter pylori infection . The assay was compared with bacterial culture and histological Giemsa stain of gastric biopsy specimens obtained from 930 patients of different ages and from different ethnic groups, with a variety of upper gastrointestinal tract symptoms . The prevalence, sensitivity, specificity, and positive and negative predictive values, respectively, were 35, 71, 90, 80, and 85% for Belgian patients aged 40 years or younger, 50, 81, 93, 92, and 83% for Belgian patients older than 40 years, and 83, 83, 79, 95, and 48% for Mediterranean patients . Using 645 serum specimens from 226 patients, we also evaluated the complement fixation test for its ability to monitor the eradication of H . pylori following antimicrobial therapy . Overall, H . pylori was eradicated from 122 patients while 104 patients remained infected with the organism . A significant decrease in antibody levels was observed 3 to 6 months after the end of therapy in the group of patients from whom H . pylori was eradicated.

Obstet Gynecol, 1992 Dec, 80(6), 912 - 6
Transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease; Cacciatore B et al.; OBJECTIVE: To evaluate transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease (PID) . METHODS: We studied 51 outpatients with a mean age of 26.8 years (range 16-52) who had a history of low abdominal pain, negative pregnancy test, and no gynecologic procedures performed during the last month . Endometrial biopsy was used for the histopathologic diagnosis . The presence of plasma cell endometritis was used as the criterion standard for the diagnosis of PID . Sonography was performed before biopsy in a blinded fashion without knowledge of the clinical findings and laboratory results except for the pregnancy test . Repeat pelvic and ultrasound examinations were performed 4 weeks after antimicrobial therapy . RESULTS: Endometrial biopsy revealed plasma cell endometritis in 13 cases (25%) . Thickened fluid-filled tubes were seen in 11 of 13 patients (85%) with plasma cell endometritis and in none of those without . Other sonographic findings associated with plasma cell endometritis were polycystic-like ovaries and free pelvic fluid . A sonogram suggestive of PID, ie, thickened fluid-filled tube with or without free pelvic fluid, had a sensitivity of 85% and a specificity of 100% for the diagnosis of plasma cell endometritis . None of the patients with a normal sonogram or simple cyst had plasma cell endometritis . Repeat examination after 4 weeks showed that the sonographic findings had resolved in 60% of the patients who had had histologic evidence of infection . CONCLUSION: Transvaginal sonography can facilitate the outpatient management of patients with suspected PID.

Radiology, 1992 Dec, 185(3), 803 - 7
The Groshong catheter: initial experience and early results of imaging-guided placement; Hull JE et al.; Fifty Groshong catheters were placed in 50 patients with use of ultrasound (US) and fluoroscopic guidance in the radiology suite: 49 were placed via the subclavian vein and one was placed via the left internal jugular vein . All (100%) attempts at catheter placement were successful . Imaging guidance affected the placement of catheters in 12 cases (24%), including four patients (8%) in whom vascular access would not have been possible with blinded percutaneous venipuncture or surgical cutdown . After a four-case learning curve period, during which one pneumothorax (2%) and two arterial punctures (4%) occurred, there were no further venipuncture-related complications . One catheter was removed because of infection (2%) and one because of allergic reaction (2%) to the antimicrobial cuff . Four patients with cutaneous infections and one with catheter-related sepsis were successfully treated with antibiotics . Results demonstrate the initial promise of imaging-guided placement of central venous access catheters when performed in the radiology suite.

Chem Pharm Bull (Tokyo), 1992 Dec, 40(12), 3352 - 4
Thunberginols C, D, and E, new antiallergic and antimicrobial dihydroisocoumarins, and thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside, new dihydroisocoumarin glycosides, from Hydrangeae Dulcis Folium; Yoshikawa M et al.; New antiallergic and antimicrobial dihydroisocoumarins, thunberginols C, D, and E, were isolated from Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SERINGE var . thunbergii MAKINO, together with new dihydroisocoumarin glycosides, thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside . Their chemical structures have been determined on the basis of chemical and physicochemical evidence . Thunberginols C, D, E, G, and (-)-hydrangenol 4'-O-glucoside showed antiallergic activity in the in vitro bioassay using the Schults-Dale reaction in sensitized guinea pig bronchial muscle, and they also exhibited antimicrobial activity against oral bacteria.

Pediatr Infect Dis J, 1992 Dec, 11(12), 1018 - 26
Age-related standards for T lymphocyte subsets based on uninfected children born to human immunodeficiency virus 1-infected women . The European Collaborative Study; Characteristics and utilization of antibody measurements in clinical studies of periodontal disease; Department of Periodontics, University of Texas Health Science Center at San AntonioThe detection and quantitation of immune responses to infections have long been used as a diagnostic tool in medical infections . Recently, increasing evidence has supported that active, specific antibody responses to selected members of the subgingival microbiota are noted in periodontitis patients . This report describes the various specificities of this antibody as they relate to periodontitis classification and prognosis . The functional aspects of the serum antibody have come under increasing scrutiny to understand better the potential immunologic mechanisms acting in the periodontium . Data are available that describe opsonizing potential, complement fixing ability, blocking functions, and anti-toxic capacity for the antibody . Longitudinal alterations in specific antibody levels are shown to relate to infection and accompany changes in the burden of a specific microorganism in the subgingival plaque . Thus, these antibody changes could be useful indicators of altered host-parasite interactions that presage a disease-active episode . Finally, studies were designed to examine the ability of antibody to reflect the effects of treatment on the disease . The results indicated that specific antibody levels change with mechanical, antimicrobial, and anti-inflammatory treatments . The findings described in this report suggest that evaluation of the level and specificity of serum antibody can be a beneficial adjunct in designing and implementing clinical studies delineating the initiation, progression, and treatment of periodontitis.

Semin Respir Infect, 1992 Dec, 7(4), 282 - 8
Chronic and recurrent pneumonia; Geppert EF; Recurrent pneumonia is defined as two or (usually) more separate episodes of lower respiratory tract infection that generally are accompanied by fever, leucocytosis, and purulent sputum production . These episodes are separated by an asymptomatic interval of at least 1 month or clearing of the chest visible by radiograph . Clinical improvement and radiological clearing should result after appropriate antimicrobial therapy . Chronic pneumonia is an illness that lasts at least 6 weeks and is caused by a microorganism . The chest radiograph usually shows diffuse or focal shadows . The incidence of either chronic or recurrent chest infections is unknown . Neither condition is common, but when present, they frequently present a difficult diagnostic challenge . Chronic pneumonias are usually caused by slow-growing organisms, such as fungi or mycobacteria . Occasionally, chronic pneumonias cannot be diagnosed, even when lung biopsy specimens are cultured or studied histopathologically . When a patient presents with recurrent pulmonary parenchymal infections, the clinician needs to identify the likely etiologies . Possible etiologies are structural abnormalities, underlying medical conditions, and immunological abnormalities, including infection by the human immunodeficiency virus (HIV).

Antibiot Khimioter, 1992 Dec, 37(12), 46 - 9
{Ciprofloxacin and other antimicrobial drugs in the treatment of disseminated peritonitis}; Levanov AV et al.; Forty two patients with general peritonitis were treated with ciprofloxacin and combinations of various antimicrobial drugs . Ciprofloxacin had the highest effect on aerobic and anaerobic microbes in the peritoneal cavity which defined the favourable clinical results in all the patients . Moreover, there were observed no disorders in the composition of the normal intestinal microflora which in the end promoted a decrease in the number of the patients with suppuration of the surgical wound.

Antibiot Khimioter, 1992 Dec, 37(12), 33 - 6
{Sensitivity of microflora isolated in the process of preparing solizyme to antimicrobial drugs}; Karlamova IuA; Microorganisms isolated from intermediate products of microbial lipase (solysime) and auxiliary raw materials, reagents and water used in the production of the enzyme belonged to diverse taxonomic groups . They were mainly susceptible to antibiotics (aminoglycosides, rifampicin, chloramphenicol and others) as well as to antiseptics and chemotherapeutics . However, certain isolates were moderately resistant to some of the antimicrobial agents (they were more frequent among Pseudomonas spp.) . The bacteriostatic action of many of the drugs was more pronounced than the bactericidal one . It was especially evident after increasing of the microbial load (from 10(5) to 10(8) CFU/ml) . At a temperature of 10 degrees C against 37 degrees C the susceptibility of the cultures to the bactericidal action of the drugs usually decreased.

Antibiot Khimioter, 1992 Dec, 37(12), 31 - 3
{Inactivating action of bacteria on the lipolytic activity of solizyme and its prevention by antibacterial drugs}; Malkova EM; Bacteria capable of producing exoproteases were isolated from intermediate products of microbial lipase . The proteolytic enzymes produced by the bacteria were able to inactivate 20 to 80 per cent of the lipase depending on the time of incubation, protease production by the contaminating microbe and the experimental conditions . Antibiotics and antiseptics inhibiting growth of bacteria prevented or limited their inactivating action on lipase . Except catamine, the tested antimicrobial drugs as such had no effect on lipase activity.

Cesk Farm, 1992 Dec, 41(9-10), 299 - 302
{Immunochemical changes in the outer membrane of Escherichia coli adapted to amine oxides}; Bukovsky M et al.; Resistant strains of Escherichia coli were obtained by stepwise cultivation in subinhibitory concentrations of two antimicrobially active amine oxides . Changes in the chemical composition of the outer membrane of the resistant strains were accompanied also by different antigenic reactions . New precipitation lines were revealed by double immunodiffusion and immuno-electrophoretic methods . The results of immunochemical analysis confirm the findings that the resistance to amphiphilic compounds is associated with the outer membrane which limits the access of antimicrobially active molecules to their sites of action in the cytoplasmic membrane.

Farmaco, 1992 Dec, 47(12), 1555 - 62
3-Diazopyrroles . Part 5 (1) . Antibacterial activity of 3-diazo-2-phenylpyrroles; Cirrincione G et al.; 3-Diazo-2-phenylpyrroles 3a-g showed antimicrobial activity against Gram-positive bacteria, whereas against Gram-negative strains the inhibitory activity is limited to derivatives 3a and 3c . The substituents at 4 and 5 positions strongly influence the inhibitory activity, but the presence of the diazo group is crucial for appearance of activity.

Cesk Epidemiol Mikrobiol Imunol, 1992 Dec, 41(6), 327 - 36
{Use of markers of hospital strains in studying the occurrence of nosocomial infections}; Sramova H et al.; The submitted paper deals with one of the possible aspects of the investigation of nosocomial infections, i.e . investigations of the properties of hospital strains, their importance and possible use . The incidence of bacterial hospital strains was investigated in a surgical department of a district hospital of the North Bohemian region in October 1990; at the time of the survey 29 nosocomial infections (36.1%) were revealed by the prevalence method . Bacterial hospital strains were isolated from patients with a nosocomial infection, from the attending staff and the hospital environment . The following markers were investigated: biotyping, phagotyping, serotyping, toxin production, sensitivity to antimicrobial substances and sensitivity to disinfectants . Based on results of marking of hospital strains 7 incidences with a possible epidemiological association were detected where the hospital strain of equal or very similar properties dominated . The results of the investigation confirmed the important participation of the attending staff in the spread of nosocomial infections, in particular via contaminated hands, and drew attention to shortcomings as regards adherence to the hygienic and epidemiological regime in the investigated department.

J Antimicrob Chemother, 1992 Dec, 30(6), 833 - 8
In-vivo activity of streptomycin and clofazimine against established infections of Mycobacterium avium complex in beige mice; Gangadharam PR et al.; Beige mice were challenged with 10(6)-10(7) cfu of Mycobacterium avium intracellulare strain 101 and 22 days later treated with streptomycin 150 mg/kg/day alone, clofazimine 20 mg/kg/day alone, streptomycin 150 mg/kg/day plus clofazimine 20 mg/kg/day, or no antimicrobial agent (untreated controls) . Both single-drug therapies partially reduced the cfu counts in spleen, liver and lungs compared with the controls however the combination was significantly more effective and completely eliminated the pathogen from the spleen and lungs of some animals after eight weeks treatment.

Arzneimittelforschung, 1992 Dec, 42(12), 1494 - 7
N-substituted 2-isocyanoarylacetamides with antimicrobial activity; Bossio R et al.; In this study, N-substituted 2-formylaminoarylacetamides (3) were obtained by the Ugi four-component reaction between isocyanides (1), aldehydes (2), and ammonium formate . The reaction products (3) were dehydrated with POCl3/NEt3 to give the title compounds (4) . The structure of the compounds 3 and 4 was confirmed by spectral data and elemental analysis . Tests of antimicrobial activity showed that compounds 4 were ineffective against E . coli and fairly active against K . pneumoniae and S . aureus . A better activity was shown against B . subtilis, but all the tested compounds showed a very good inhibitory effect against C . albicans.

J Chemother, 1992 Dec, 4(6), 347 - 52
Antimicrobial activity of benzydamine, a non-steroid anti-inflammatory agent; Fanaki NH et al.; The antimicrobial activity of benzydamine (BD), a non-steroid anti-inflammatory agent, was studied using different techniques against 38 strains belonging to 12 microbial species comprising bacteria, yeasts and a fungus . The minimum inhibitory concentrations, minimum lethal concentrations, per cent survivors after 30-minute exposure to BD (0.1%), growth curves of 7 selected organisms in subinhibitory BD concentrations and killing times for clinical isolates at different BD levels (0.05-0.15%) were determined . The data obtained throughout this study show that BD is a general antimicrobial agent with a rapid biocidal activity against a variety of organisms at concentrations less than those advocated for treatment of inflammatory conditions.

Int J Pept Protein Res, 1992 Dec, 40(6), 507 - 14
Synthesis and characterization of defensin NP-1; Rao AG et al.; Defensins are a group of small, cationic, antimicrobial proteins found in the cytoplasmic granules of neutrophils and macrophages of a variety of mammalian species . One such defensin, NP-1, isolated from rabbit neutrophils, has been shown to consist of 33 amino acids rich in arginine and cysteine residues . We have synthesized NP-1 on an Applied Biosystems Model 431A peptide synthesizer using FastMoc chemistry involving HBtu {2-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate} activation for coupling amino acids . The linear peptide was folded by air oxidation to the biologically active form containing three disulfide bonds and purified by reverse phase chromatography . The amino acid sequence of the synthetic peptide was confirmed by Edman degradation . Molecular weight determination by plasma desorption mass spectroscopy (PDMS) gave a value of 3898.6, in agreement with the expected molecular weight of 3898 . The biological activity of the synthetic peptide, as measured by its antifungal activity against several pathogenic fungi, was indistinguishable from that of the natural NP-1 . Also, the CD spectrum was equivalent to that of natural NP-1, indicating conformational identity of the two species.

J Antimicrob Chemother, 1992 Dec, 30(6), 839 - 42
Inhibition of nitric oxide synthesis improves survival in a murine peritonitis model of sepsis that is not cured by antibiotics alone; Teale DM et al.; Inhibition of nitric oxide synthesis was investigated in a murine model of advanced sepsis in which antibiotic therapy alone did not improve survival . Seven hours after receiving a lethal intraperitoneal challenge with live Escherichia coli, mice were given either NG-monomethyl-L-arginine (L-NMMA) intravenously, imipenem-cilastatin subcutaneously or a combination of both . L-NMMA (3-300 mg/kg) or imipenem-cilastatin (10 or 50 mg/kg) given alone did not improve survival; co-administration of L-NMMA and either 10 or 50 mg imipenem-cilastatin/kg improved survival significantly . These findings suggest that nitric oxide contributes to the morbidity associated with advanced sepsis and that nitric oxide synthase inhibition may improve the efficacy of conventional antimicrobial treatment of severe infections.

Antimicrob Agents Chemother, 1992 Dec, 36(12), 2645 - 51
The role of guanosine-3',5'-bis-pyrophosphate in mediating antimicrobial activity of the antibiotic 3,5-dihydroxy-4-ethyl-trans-stilbene; Sundar L et al.; The mode of action of 3,5-dihydroxy-4-ethyl-trans-stilbene (ES), an antibiotic produced by Xenorhabdus luminescens symbiotically associated with an entomopathogenic nematode, was investigated . ES was active against gram-positive and a number of gram-negative bacteria . In susceptible bacteria this antibiotic caused the inhibition of total RNA synthesis and, to a lesser extent, protein synthesis . At or above MICs, ES triggered a substantial accumulation of an intracellular regulatory compound, guanosine-3',5'-bis-pyrophosphate (ppGpp) . This response was also noticed in species of bacteria which have previously not been shown to use ppGpp as a regulatory molecule . The involvement of ppGpp in antibiotic action was confirmed by using an isogenic stringent and a relaxed pair of Escherichia coli strains . The fact that the accumulation of ppGpp was correlated with the susceptibility of various gram-positive and gram-negative bacteria to ES suggests that this nucleotide is involved in the regulation of RNA synthesis and growth in all these microorganisms . Thus, inhibition of RNA synthesis via an increase in ppGpp concentrations may represent a mechanism that is prevalent among most bacteria and one that could be exploited for achieving a rapid inhibition of bacterial growth.

Rinsho Ketsueki, 1992 Dec, 33(12), 1869 - 74
{Recombinant human granulocyte-colony stimulating factor (rhG-CSF) treatment for spleen abscess and periostitis in a patient with chronic granulomatous disease}; Nakajima F et al.; A 9-year-old boy with chronic granulomatous disease was hospitalized on May, 1991, because of continued fever and pain in the right elbow . Increased bone intensity at the distal end of right humerus on x-ray and a 33 x 36 mm space-occupying lesion in the spleen on abdominal CT scan were recognized . Under a diagnosis of periosteitis and spleen abscess, intravenous infusion of rhG-CSF at a dose of 200 micrograms/m2/day was started in combination with antimicrobial therapy . Fever, tenderness, swelling in the right elbow and inflammatory indices improved three weeks after the institution of therapy . Hydrogen peroxide (H2O2) formation by neutrophil increased significantly, although intermittently, during the therapy . The spleen abscess had completely vanished on CT scan on February, 1992 . The therapy was well tolerated and no significant side effects were observed . The use of rhG-CSF in combination with potent antibiotics is recommended for patients with serious infections in chronic granulomatous disease to avoid a fatal course.

P R Health Sci J, 1992 Dec, 11(3), 139 - 46
{Interferon and its potential use in the treatment of infectious diseases}; Rios Olivares E; Modern recombinant biotechnology has made possible the production of large amount of interferons and their use as immunotherapeutic agents . Most of the biological, physical and chemical characteristics of interferons has been established, including their classification, genetic structure, chemical composition and possible mechanisms of action . Interferons have been utilized in clinical studies with human and experimental animals against bacterial, mycotic, parasitic and viral infections . Success has been reported mainly when administered prophylactically against acute infections . Favorable results have been obtained, both prophylactic and therapeutically, in some chronic diseases and in those in which the microorganism has an intracellular phase during its life cycle . Moreover, a promising future has been suggested for the combined use of interferon with other antimicrobial drugs.

Nippon Hinyokika Gakkai Zasshi, 1992 Dec, 83(12), 1999 - 2004
{Multifactorial analysis of the pyuria after transurethral prostatectomy}; Fujita K et al.; Multifactorial analysis on 395 patients revealed important factors which prolong the pyuria after transurethral prostatectomy . They were the age of the patient, anemia and leukocytosis before surgery . These are factors which relate with the defense mechanism of the patient . Local factors, such as the duration of indwelling urethral catheter, the size of the prostate or prostatic bed and preoperative infection, were not so important for prolonging the pyuria after transurethral prostatectomy . The time of the resection and weight of the prostate had an intimate relation each other, and the former was the more important factor . The use of antimicrobials probably controlled these local risk factors, thus making them unimportant in the prolongation of the pyuria after transurethral prostatectomy.

Biochem Biophys Res Commun, 1992 Nov 30, 189(1), 184 - 90
Brevinin-1 and -2, unique antimicrobial peptides from the skin of the frog, Rana brevipoda porsa; Morikawa N et al.; Two unique antimicrobial peptides named brevinin-1 and -2 were isolated from the skin of the frog, Rana brevipoda porsa . Both of the peptides did not have any structural homology with bombinin nor magainin; the frog skin derived-antimicrobial peptides isolated from Bombina and Xenopus, nor even with other known antimicrobial peptides of non-amphibian origin . The minimum inhibitory concentration of brevinin-1 against the growth of St . aureus and E . coli was determined to be 8 micrograms/ml and 34 micrograms/ml while that of brevinin-2 was 8 micrograms/ml and 4 micrograms/ml, respectively, indicating the difference of the two peptides in the antimicrobial selectively on Gram-positive and Gram-negative bacteria.

Biochemistry, 1992 Nov 24, 31(46), 11357 - 64
NMR studies of defensin antimicrobial peptides . 2 . Three-dimensional structures of rabbit NP-2 and human HNP-1; Pardi A et al.; The solution structure of two homologous naturally occurring antimicrobial peptides, rabbit defensin NP-2 and human defensin HNP-1, have been determined by two-dimensional nuclear magnetic resonance spectroscopy, distance geometry, and restrained molecular dynamics calculations . The structure of these defensins consists of an antiparallel beta-sheet in a hairpin conformation, a short region of triple-stranded beta-sheet, several tight turns, and a loop region that has a well-defined local structure but with a global orientation that is not well-defined with respect to the rest of the molecule . The solution structures of these two peptides are compared with the solution and crystal structures of two other homologous defensins . The structures for the defensins are also compared with known structures of other naturally occurring antimicrobial peptides.

Biochemistry, 1992 Nov 24, 31(46), 11348 - 56
NMR studies of defensin antimicrobial peptides . 1 . Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1; Zhang XL et al.; Two-dimensional nuclear magnetic resonance spectroscopy has been used to make resonance assignments of the proton spectra of two defensin antimicrobial peptides, human neutrophil peptide HNP-1 and rabbit neutrophil peptide NP-2 . The secondary structures of these peptides were determined from analysis of the proton-proton NOEs and from the positions of slowly exchanging amide protons . Both peptides contain a long stretch of a double-stranded antiparallel beta-sheet in a hairpin conformation that contains a beta-bulge, a short region of triple-stranded beta-sheet, and several tight turns . The NMR results clearly show that HNP-1 forms a dimer or higher order aggregate in solution and that Pro8 exists as a cis peptide bond . The NMR data on these peptides are compared with NMR data for a homologous peptide NP-5 {Bach, A . C., Selsted, M . E., & Pardi, A . (1987) Biochemistry 26, 4389-4397} . Analysis of the conformation-dependent proton chemical shifts shows that it is not possible to confidently judge the structural similarity of the three defensins from chemical shift data alone . However, comparison of the 3JHN alpha coupling constants in NP-2 and NP-5 indicates that the backbone conformations for these peptides are very similar . A more detailed comparison of the solution conformations of the defensins peptides is made in the following paper in this issue where the NMR data are used as input for distance geometry and molecular dynamics calculations to determine the three-dimensional structures of HNP-1 and NP-2.

J Biol Chem, 1992 Nov 15, 267(32), 23216 - 25
Paneth cells of the human small intestine express an antimicrobial peptide gene; Jones DE et al.; Mucosal surfaces of several organ systems are important interfaces for host defense against microbes . Recent evidence suggests that antimicrobial peptides contribute to the defense of these surfaces . Defensins are one family of antimicrobial peptide, but their known distribution in humans has been limited to four members found in cells of myeloid origin . We sought to determine if the human defensin family was more complex . We found that the family of human defensins is diverse and is not restricted to expression in leukocytes . Southern blot and genomic clone analyses reveal that numerous defensin-related sequences are present in the human genome . A gene for a new human defensin family member was characterized . This gene, designated human defensin-5, is highly expressed in Paneth cells of the small intestine . This is the first example of an antimicrobial peptide gene expressed in an epithelial cell in humans . The data support the hypotheses that epithelial defensins equip the human small bowel with a previously unrecognized defensive capability which would augment other antimicrobial defenses.

Arch Biochem Biophys, 1992 Nov 15, 299(1), 30 - 7
Superoxide formed from cigarette smoke impairs polymorphonuclear leukocyte active oxygen generation activity; Tsuchiya M et al.; Reactive free radicals contained in cigarette smoke (CS) and compromised phagocytic antimicrobial activities including those of polymorphonuclear leukocytes (PMNs) have been implicated in the pathogenesis of severe CS-related pulmonary disorders . In CS-exposed buffer solutions, O2- . was the predominant generated reactive oxygen species, as demonstrated by lucigenin-amplified chemiluminescence and electron spin resonance (ESR) spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) . When PMNs were incubated in this buffer, phorbol 12-myristate 13-acetate (PMA)-stimulated active oxygen production and coupled O2 consumption were strongly impaired without appreciably affecting PMN viability (1-min exposure inhibited active oxygen production by 75%) . Superoxide dismutase (SOD) totally protected and an iron chelator, diethylenetriaminepentaacetic acid (DETAPAC), also protected the CS-exposed PMNs, suggesting that generated O2- . was an initiating factor in the impairment and OH . generation was a subsequent injurious factor . Pretreatment of PMNs with antioxidants such as alpha-tocopherol and dihydrolipoic acid (DHLA) was partially protective . The results suggest that (i) O2- . is probably generated in the upper and lower respiratory tract lining fluid when they come in contact with CS; (ii) such generated O2- . can primarily impair PMN capabilities to generate reactive oxygen species; and (iii) since these effects may contribute to the pathogenesis of CS-related lung diseases, prior supplementation with antioxidants such as alpha-tocopherol or DHLA might be successful in preventing these deleterious effects.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S339 - 46
General guidelines for clinical bacteriology . Infectious Diseases Society of America and the Food and Drug Administration; Thrupp LD et al.; This guideline summarizes recommendations for (1) developing cogent procedures for diagnosis and antimicrobial susceptibility testing; (2) developing quality-control parameters for the microbiological components of clinical trials; (3) continually updating U.S . Food and Drug Administration (FDA) guidelines; (4) reviewing microbiological recommendations from other groups, such as Microbiology Subcommittees of the National Committee for Clinical Laboratory Standards; and (5) improving the microbiological aspects of FDA package inserts for antimicrobial drugs . Sensitive and specific methods for isolation and identification of pathogens are essential to the proper conduct of clinical trials . Susceptibility tests should be performed in an accurate and reproducible fashion . Verification of results in a reference laboratory is encouraged to monitor quality control.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S313 - 38
Evaluation of new anti-infective drugs for surgical prophylaxis . Infectious Diseases Society of America and the Food and Drug Administration; Gorbach SL et al.; It has been established by substantial research that antimicrobial prophylaxis for various surgical procedures can reduce the risk of postoperative morbidity and mortality . When the incidence of infectious complications is high, the reduction with prophylaxis is most dramatic . However, even for many "clean" procedures (vascular procedures, total joint replacement), the small reduction in potentially calamitous complications justifies the use of prophylaxis . Many issues of detail remain unanswered: timing and duration of administration of antimicrobial drug; type of drug; use of topical anti-infective agents as ancillary measures; and choices for high-risk individuals and others ordinarily excluded from clinical trials . An approach to the conduct of clinical trials of anti-infective drugs for surgical prophylaxis is provided . Both general guidelines and specific recommendations for total hip replacement, colorectal operations, appendectomy, and transurethral resection of the prostate are included.

J Heart Lung Transplant, 1992 Nov-Dec, 11(6), 1127 - 32
Cyclosporine interactions with miconazole and other azole-antimycotics: a case report and review of the literature; Horton CM et al.; Several antimicrobial drugs have been shown to pharmacokinetically interact with cyclosporine . On two separate occasions, we observed increases in cyclosporine plasma concentrations during concomitant miconazole therapy in a heart transplant patient with an infection secondary to Pseudallescheria boydii . To our knowledge, no interaction between cyclosporine and miconazole has previously been reported . In addition, drug interactions were observed between cyclosporine and ketoconazole and possibly between cyclosporine and SCH 39304, an investigational azole-antifungal agent . No interaction was noted between cyclosporine and fluconazole . In general, clinicians should anticipate drug interactions between cyclosporine and azole-antimycotic agents.

N Z Med J, 1992 Nov 11, 105(945), 441 - 4
Ceftriaxone for paediatric bacterial meningitis: a report of 62 children and a review of the literature; Craig JC et al.; AIM: The purpose of this prospective study was to document the efficacy of ceftriaxone in the treatment of childhood bacterial meningitis in a general paediatric unit . METHODS: All children presenting with bacterial meningitis to Christchurch Hospital between January 1987 and June 1991 were enrolled in this prospective study and received ceftriaxone 100 mg/kg/d for seven days . Outcome was defined by parameters including mean time to fever defervescence, prolonged fever, days in hospital, seizures, and other acute neurological sequelae, requirement for ventilation, mortality and morbidity . Audiology was performed at six weeks and again at three months if abnormal . Neurodevelopmental assessment was performed at three months . Side effects were recorded . RESULTS: There were 62 evaluable children . The mortality rate was 4.8% (3 children) . Two children (3.4%) had clinically detectable neurological sequelae at the three month assessment . The mean duration of stay was 8.7 nights . Five children (8%) required ventilation . Mild self limiting diarrhoea occurred in 29% . CONCLUSIONS: Ceftriaxone is an effective, safe and well tolerated antimicrobial for the treatment of childhood meningitis . It compares favourably with other equipotent antimicrobials . With a relatively long half life once daily administration is possible with a cost advantage.

JPEN J Parenter Enteral Nutr, 1992 Nov-Dec, 16(6), 529 - 32
Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide; Pappo I et al.; Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements . Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production . In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis . Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels . Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group . The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin . We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN.

J Antimicrob Chemother, 1992 Nov, 30(5), 643 - 50
The in-vitro bactericidal activities of combinations of antimicrobial agents against clinical isolates of Mycobacterium avium-intracellulare; Kent RJ et al.; The in-vitro activities of five antimicrobial agents (rifabutin, clarithromycin, ethambutol, ciprofloxacin and amikacin), alone and in combination, were evaluated against 21 strains of Mycobacterium avium-intracellulare isolated from patients with AIDS . The combined activities of these agents were studied on solid medium by a full chequerboard method . Synergy was demonstrated most frequently (28-71% of isolates) with those combinations that included ethambutol . In killing curve experiments where double and triple combinations of agents were tested against two of the strains, 99% kill was achieved in seven days at concentrations well below those that are attainable in serum . However, an additive rather than a synergic effect was seen in most instances . Although ciprofloxacin alone had the greatest bactericidal activity against these two strains, its activity was antagonized in the presence of rifabutin; this antagonism became inapparent when a third agent was added . Demonstration of bactericidal activity in broth culture may be more relevant than the results of susceptibility testing on solid medium when choosing antimicrobial therapy for patients with this infection.

Ear Nose Throat J, 1992 Nov, 71(11), 599 - 603
Frontal sinusitis with chronic epidural abscess: a case presentation; Reader ME et al.; The incidence of intracranial complications from acute frontal sinusitis has decreased with improved antimicrobial and surgical therapy . However, the physician must maintain a keen awareness and thoroughly investigate any possible signs of intracranial spread . This article discusses a case in which a chronic epidural abscess developed after inadequate therapy was rendered . It also reviews the presentation of and the factors leading to the development of intracranial complications . The treatment required is to eradicate the disease present and prevent future sinusitis.

Farmaco, 1992 Nov, 47(11), 1395 - 405
Synthesis and antimicrobial activity of some pyrrole derivatives . V: 5-Aryl-3-ethoxycarbonyl-2-(4-substituted piperazino)pyrrole derivatives; Cocco MT et al.; The synthesis of new 5-aryl-3-ethoxycarbonyl-2-piperazinopyrrole derivatives is reported . The new compounds were tested in vitro for their antimicrobial activity . Compound 11 was the most active against the Gram-positive microorganisms.

Decubitus, 1992 Nov, 5(6), 32 - 41
The treatment of osteomyelitis underlying pressure ulcers; Deloach ED et al.; Osteomyelitis is recognized as an often intractable hindrance to healing in the deep pressure ulcer . The mainstays of treatment of this disease have traditionally been surgical debridement followed by muscle flap revascularization, supplemented by antibiotic coverage . Hyperbaric oxygenation has also been shown to be effective in healing refractory osteomyelitis when used as an adjunct to surgical and medical therapy . This review defines the disease, and presents a current literature review and discussion of its treatment, including adequacy of debridement, options for wound closure, appropriate antimicrobial strategy, and the role of hyperbaric oxygenation . A short review of investigational modalities is also included.

Antimicrob Agents Chemother, 1992 Nov, 36(11), 2552 - 5
Iontophoresis generates an antimicrobial effect that remains after iontophoresis ceases; Davis CP et al.; Iontophoresis required chlorine-containing compounds in the medium for effective microbial population reduction and killing . After iontophoresis ceased, the antimicrobial effect generated by iontophoresis remained but slowly decreased . Antimicrobial effects of iontophoresis may be related to the generation of short-lived chlorine-containing compounds.

Antimicrob Agents Chemother, 1992 Nov, 36(11), 2387 - 91
In vitro activities of fleroxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use to treat guinea pigs with L . pneumophila pneumonia; Edelstein PH et al.; The activities of fleroxacin against 22 clinical Legionella isolates were determined by agar and broth microdilution susceptibility testing . The fleroxacin MIC required to inhibit 90% of strains tested on buffered charcoal yeast extract agar medium supplemented with 0.1% alpha-ketoglutarate was 0.64 micrograms/ml and was 0.04 microgram/ml when testing was done with buffered yeast extract broth supplemented with 0.1% alpha-ketoglutarate . Fleroxacin (0.25 microgram/ml) reduced the bacterial counts of two L . pneumophila strains grown in guinea pig alveolar macrophages by 1 log10 CFU/ml, but regrowth occurred over a 3-day period; fleroxacin was significantly more active than erythromycin in this assay . Single-dose (10 mg/kg of body weight given intraperitoneally) pharmacokinetic studies performed in guinea pigs with L . pneumophila pneumonia revealed peak levels in plasma and lungs to be 3.3 micrograms/ml and 3.5 micrograms/g, respectively, at 0.5 h and 0.8 microgram/ml and 0.8 microgram/g, respectively, at 1 h . The half-life of the terminal phase of elimination from plasma and lung was approximately 2 h . All 17 infected guinea pigs treated with fleroxacin (10 mg/kg/day) for 2 days survived for 14 days post-antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of fleroxacin for 5 days . Only 1 of 16 animals treated with saline survived . The animals treated with fleroxacin for 2 days lost more weight and had higher temperatures than those treated with the antibiotic for 5 days . Fleroxacin is effective against L . pneumophila in vitro and in a guinea pig model of Legionnaires' disease . Fleroxacin should be evaluated as a treatment for human Legionnaires' disease.

Ital J Gastroenterol, 1992 Nov-Dec, 24(9 Suppl 2), 14 - 6
Treatment of hepatic encephalopathy with non-absorbable antibiotics; Festi D et al.; Hepatic encephalopathy represents a well known neuropsychiatric syndrome in patients with either acute or chronic impaired liver function and is characterized by disturbance of consciousness, personality and intellectual capacity, altered neuromuscular activity and electroencephalographic abnormalities . The pathogenesis of the syndrome is still unknown, although important roles are ascribed to circulating gut-derived toxins of nitrogenous origin and to changing in central neurotransmission . Therefore, treatment is aimed to reduce the production and absorption of gut-derived toxins and to modify central neurotransmission balance . Among the different therapeutic approaches proposed for the management of hepatic encephalopathy, antimicrobial agents, alone or in combination with non-absorbable disaccharides, represent an important step, being able to reduce the production and absorption of ammonia, a compound of key importance in the pathogenesis of hepatic encephalopathy.

Minerva Ginecol, 1992 Nov, 44(11), 587 - 90
{Prophylactic and therapeutic use of ceftriaxone in cesarean section}; Giannone R et al.; Authors did the antibiotic-prophylaxis with ceftriaxone in twenty cesarean sections (1 phial EV) . Prophylaxis was sufficient in thirteen cases; on the other hand, in the remaining seven prophylaxis was followed by the three days therapy (1 phial EV) . A good tolerance of the medicine was revealed in all cases . Moreover, it was tested a wide antimicrobial action with resolution of all the verified infections, except for one bacterial resistance case where some other antibiotic was used.

J Nat Prod, 1992 Nov, 55(11), 1620 - 5
Studies on the synthesis of sesquiterpene lactones, 14 . Syntheses of (-)-arbusclin D and (+)-4-EPI-arbusclin D: the stereochemical assignment of arbusclin D; Ando M et al.; Efficient syntheses of (-)-arbusclin D and (+)-4-epi-arbusclin D are reported . By these syntheses the C-4 stereochemistry of arbusclin D and the absolute configuration of (-)-arbusclin D have been determined to be a s shown in structure 1 . The biological activities, such as cytotoxic activity toward P-388 lymphocytic leukemia, plant growth regulating activity, and antimicrobial activity of compounds 1, 3, 7, 9, 12, and 14 were also studied.

Compr Ther, 1992 Nov, 18(11), 35 - 42
An overview of antimicrobial therapy; Liu C; Dealing with infections is an integral part of clinical practice . The vast number of antimicrobial agents available, with new ones being introduced constantly, behooves practitioners to keep abreast of the properties, antimicrobial activities, clinical uses and possible adverse effects of these agents . This article attempts to present an overview on several classes of antimicrobial agents commonly used in our daily practices, with the hope of steering our colleagues toward rational and judicious usage of these potent medications.

Chem Pharm Bull (Tokyo), 1992 Nov, 40(11), 3121 - 3
Thunberginols A, B, and F, new antiallergic and antimicrobial principles from hydrangeae dulcis folium; Yoshikawa M et al.; Six new antiallergic and antimicrobial principles, thunberginols A, B, C, D, E, and F, were isolated from Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla SERINGE var . thunbergii MAKINO . The chemical structures of thunberginols A, B, and F have been determined on the basis of chemical and physiocochemical evidence . Thunberginols A, B, and F showed more potent antiallergic activity than phyllodulcin, hydrangenol, and AA-861 in the in vitro test using the Schults-Dale reaction in sensitized guinea pig bronchial muscle . Thunberginols A, B, and F also exhibited antimicrobial activity against oral bacteria.

Ann Pharmacother, 1992 Nov, 26(11), 1447 - 51
Intravenous-to-oral stepdown program: four years of experience in a large teaching hospital; Frighetto L et al.; OBJECTIVE: To assess the impact of an intravenous-to-oral (iv-po) stepdown program on the relative use of oral and parenteral dosage forms of select antimicrobials . DESIGN: A retrospective review of drug utilization records before and after a trial comparing metronidazole and clindamycin prescribing trends from a 12-month baseline period to a four-year follow-up period . SETTING: One thousand-bed Canadian tertiary care referral teaching center . INTERVENTION: An authorized iv-po stepdown program was developed to promote the oral route of drug administration . Reminders of iv-po stepdown were produced for metronidazole and clindamycin and these notes were sent to nursing units with the parenteral dosage form . The notes then were attached to the front of the health record to serve as a reminder to prescribers that an equally effective, well-tolerated, and less-expensive oral dosage form was available for use . RESULTS: A 44 percent relative increase in the use of oral metronidazole and a 79 percent relative increase in the use of oral clindamycin occurred . When acquisition and delivery costs were considered, cumulative cost savings from 1988 to 1991 resulted for metronidazole ($31,920) and clindamycin ($53,880) . CONCLUSIONS: This intervention represents a simple yet effective method of promoting a process of stepdown from parenteral to oral antibiotic therapy.

Ann Pharmacother, 1992 Nov, 26(11), 1358 - 65
Mathematical examination of dual individualization principles . (III): Development of a scoring system for pneumonia staging and quantitation of response to antibiotics: results in cefmenoxime-treated patients; Luzier A et al.; OBJECTIVE: In order to quantitatively express the important, time-related aspects of response to antimicrobial therapy in patients with pneumonia, we required validated measures of the time course of events during the infection . To quantitate the changes in clinical status in relation to changes in cultures, we developed a scoring system to be used for patient assessment during therapy . DESIGN: Retrospective data collection, prospective analysis of factors . SETTING: Intensive care unit, Millard Fillmore Hospital . PATIENTS: Twenty-eight patients with nosocomial pneumonia . MAIN OUTCOME MEASURES: Clinical parameters were assessed daily for the duration of antimicrobial therapy . Using linear regression, the rate of clinical change in each patient treated was quantified . Eradication of the pathogen was determined by serial cultures of the infection site . RESULTS: Seventeen of the patients demonstrated eradication of the organism, and 11 demonstrated persistence of the pathogen (7 were considered colonization) . The system described the patients at baseline in that the mean baseline scores were similar in both groups of patients (p = 0.79) . Patients in whom the pathogen was eradicated showed a rate of clinical improvement significantly different from those who had persistence of the organism (p = 0.04) . In patients demonstrating eradication, the time to eradication inversely correlated with the rate of clinical improvement (p < 0.05) . Of the ten parameters descriptive of the disease, those most sensitive to change after eradication of bacteria were body temperature, bacterial Gram stain, white blood cell Gram stain, and volume of sputum . CONCLUSIONS: In this set of pneumonia patients, the scoring system effectively quantified both baseline and time-related changes in clinical status . The system distinguished between the clinical course of the patient with organism eradication versus organism persistence . A shorter time to eradication was associated with a better clinical response . Prospective study of the system will determine its sensitivity.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S96 - 8
Special issues in clinical trials of new anti-infective drugs for the treatment of sexually transmitted diseases . Infectious Diseases Society of America and the Food and Drug Administration; Handsfield HH et al.; Several special issues arise in relation to clinical trials of therapy for sexually transmitted diseases . These issues include the desirability of including adolescents and both pregnant and nonpregnant women in the trial, the use of unapproved control regimens, problems with antimicrobial susceptibility testing due to inadequate methodology and the need for prompt treatment, the need to assess agents for treatment of syndromes of unknown microbial etiology, toxicity considerations related to the use of single-dose regimens, management of the sexual partners of the participants in the trial, analysis of data despite the high frequency of minor protocol violations, sexual reexposure to infection during the trial, and the potential for loss, alteration, or falsification of data because of the relative simplicity of the usual protocol design and the diagnostic reliance on specimens that are routinely discarded.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S206 - 15
Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients . Infectious Diseases Society of America and the Food and Drug Administration; Hughes WT et al.; The use of empirical antimicrobial therapy has significantly reduced the morbidity and mortality associated with untreated infections in febrile neutropenic patients . This guideline describes clinical trials of the safety and efficacy of new antimicrobial drugs in this population of patients . Fever and neutropenia should be precisely defined in each protocol . Patients should be randomized to treatment with a new or active-control drug regimen, stratified on the basis of type of cancer and age, and treated until resolution--as defined in the protocol--is attained . Outcome should be assessed both for cases with a defined microbial etiology and for those without . Final microbiological outcome is important for cases with identified pathogens, but clinical outcome is paramount.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S177 - 81
Evaluation of new anti-infective drugs for the treatment of infections of prosthetic hip joints . Infectious Diseases Society of America and the Food and Drug Administration; Norden C et al.; Infections of a prosthetic hip are of three types: acute contiguous, chronic contiguous, and hematogenous . Acute contiguous infections result from contamination of the operative field at the time of surgery; clinical manifestations of infection become apparent within 6 months . Chronic contiguous infections are diagnosed 6-24 months postoperatively and are believed to be caused by intraoperative contamination . Hematogenous seeding of prosthetic joints accounts for infections that develop > or = 2 years after surgery . Fever and pain or dysfunction of the joint may be the only signs or symptoms of prosthetic hip joint infection . Definitive diagnosis is established by culture of a needle aspirate from the joint space or by intraoperative culture . Prospective, randomized, double-blind or evaluator-blinded, active-control comparative studies are preferable to open trials . Success rates 10-14 weeks after completion of a 4- to 6-week course of antimicrobial therapy should be > or = 90%.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S172 - 6
Evaluation of new anti-infective drugs for the treatment of acute suppurative arthritis in children . Infectious Diseases Society of America and the Food and Drug Administration; Nelson JD et al.; Diagnostic criteria for bacterial suppurative arthritis include the demonstration of an inflammatory exudate by aspiration of synovial fluid and the isolation of bacteria from cultures of synovial fluid and/or blood . Clinical manifestations include joint effusion, swelling, tenderness, and pain, with or without redness of the overlying skin . Management consists of antimicrobial therapy, measures designed to relieve symptoms, surgical drainage of infected fluid, and physical therapy . Studies of new anti-infective therapy should be limited to cases of bacterial origin . Prospective, randomized, double-blind, or evaluator-blinded, active-control comparative clinical trials should be performed . Clinical response is characterized as success (cure), failure, or indeterminate outcome . The most common successful microbiological outcome is presumptive eradication . Follow-up should continue for 1 year before the final assessment.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S155 - 61
Evaluation of new anti-infective drugs for the treatment of osteomyelitis in adults . Infectious Diseases Society of America and the Food and Drug Administration; Mader JT et al.; Cases of osteomyelitis can be divided into four categories: acute hematogenous, vertebral, secondary to a contiguous focus of infection without vascular disease, and secondary to a contiguous focus of infection with vascular disease . Each category may be further divided into acute and chronic forms . Clinical symptoms persisting for > or = 10 days correlate roughly with the development of necrotic bone and chronic osteomyelitis . Patients enrolled in clinical trials should generally be > or = 12 years of age . Prior antimicrobial treatment does not exclude patients if the culture of a bone sample obtained at the time of enrollment yields pathogenic bacteria . Randomized, double-blind, active-control comparative studies are encouraged . Clinical outcome should be assessed during therapy and within 5-9 days, 4-6 weeks, and 11-13 months after completion of therapy . In the final assessment, clinical appraisal is paramount.

Clin Infect Dis, 1992 Nov, 15 Suppl 1, S131 - 9
Evaluation of new anti-infective drugs for the treatment of sexually transmitted chlamydial infections and related clinical syndromes . Infectious Diseases Society of America and the Food and Drug Administration; Handsfield HH et al.; This guideline addresses clinical trials of new antimicrobial agents in the treatment of uncomplicated genital infections caused by Chlamydia trachomatis and of syndromes resembling chlamydial infections . The most common clinical manifestations of chlamydial infection are urethritis in men and mucopurulent cervicitis in women . However, many chlamydial infections are not associated with inflammatory symptoms or signs . Culture is the diagnostic standard for defining the presence of C . trachomatis, although nonculture tests may be used in screening patients for enrollment in clinical trials . Susceptibility testing for C . trachomatis is laborious and difficult to standardize; only a few clinical isolates need to be tested in vitro . Prospective, randomized, double-blind, active-control comparative studies are recommended . Eradication of C . trachomatis defines both microbiological success and overall cure for chlamydial infection, but clinical and nonmicrobiological laboratory criteria are paramount in assessing the therapeutic response in nonchlamydial urethritis or cervicitis.

J Infect, 1992 Nov, 25(3), 303 - 6
Primary abdominal actinomycosis in a diabetic woman--an intractable disease; Raz R et al.; Primary abdominal actinomycosis is very unusual . Only five previous cases have been reported in the English literature . We describe the case of a 57-year-old diabetic woman with primary abdominal actinomycosis, refractory to several antimicrobial regimens and surgical procedures . We conclude that primary abdominal actinomycosis in such a diabetic woman is an intractable disease.

J Antibiot (Tokyo), 1992 Nov, 45(11), 1759 - 62
APHE-1 and APHE-2, two new antimicrobial and cytotoxic antibiotics . II . Physico-chemical properties and structure elucidation; Fidalgo ML et al.; Two new pyrazolo-isoquinolinone antibiotics, APHE-1 and APHE-2, have been isolated from the culture filtrate and mycelia of Streptoverticillium griseocarneum NCIMB 40447 . Molecular formulae were established as C13H12N2O for APHE-1 and C14H14N2O for APHE-2, by elemental analysis, NMR and mass spectra . 2D NMR techniques (1H-1H COSY-45 and 1H-13C correlated spectroscopy) have been applied to establish their structures.

J Antibiot (Tokyo), 1992 Nov, 45(11), 1753 - 8
APHE-1 and APHE-2, two new antimicrobial and cytotoxic antibiotics . I . Taxonomy, fermentation, isolation and biological activity; Fidalgo ML et al.; APHE-1 and APHE-2 are two new antibiotics produced by Streptoverticillium griseocarneum NCIMB 40447 . They exhibited a remarkable cytotoxic activity against several tumor cell lines from different origin . Furthermore, they showed weak antimicrobial activity against Gram-positive bacteria, filamentous fungi and yeasts.

Diabetes Care, 1992 Nov, 15(11), 1449 - 50
Hemophilus influenza infection of an implantable insulin-pump pocket; Levy RP et al.; OBJECTIVE--To increase awareness of adverse events associated with the use of implantable insulin pumps . RESEARCH DESIGN AND METHODS--A descriptive case report of a pump implant infection . RESULTS--This is a case report of one implanted insulin pump-pocket infection among a series of 15 patients . After exposure to a child with a respiratory infection on PID 30, V.L.C . (the patient) developed a fulminant pump-pocket infection . H . influenza was recovered from it . Despite aggressive antibiotic therapy, the infection could not be controlled . Insulin delivery ceased, and the pump was explanted . The pump-pocket infection rapidly resolved with pump removal, permitting later reimplantation . CONCLUSIONS--We have adopted the American Heart Association indications and antimicrobial prophylaxis regimens recommended for prevention of endocarditis in patients with prosthetic values for patients with implanted insulin pumps.

Arch Oral Biol, 1992 Nov, 37(11), 963 - 8
The distribution of the antimicrobial protein, calprotectin, in normal oral keratinocytes; Eversole LR et al.; Calprotectin is a heterodimeric peptide isolated from neutrophil cytosol that exhibits profound antimicrobial effects . Using monoclonal antibody MAC 387, calprotectin was found to be expressed in oral keratinocytes from normal, non-inflamed oral mucosa . Orthokeratinized sites including the attached gingiva and hard palate expressed low levels of calprotectin with a restricted pattern; immunoreactants were identified only within subcorneal keratinocytes . Parakeratinized mucosa from the lips, soft palate, tongue and buccal mucosa expressed calprotectin in a more widespread, yet variable pattern, immunoreactants being detectable in only a portion of the spinous layer in some cases whereas in others the pattern of expression was more topographically diffuse . Antigen was not detected in basilar and lower strata cells . Both cytoplasmic and nuclear decoration could be identified . The results indicate that oral mucosa harbours an antimicrobial deterrent to micro-organisms that may enhance the physical epithelial barrier of host defence.

Orthopedics, 1992 Nov, 15(11), 1331 - 5
Lyme disease: an orthopedic perspective; Lawrence SJ; The incidence of Lyme disease is increasing . This spirochetal infection may frequently manifest itself with joint involvement without characteristic dermatologic signs or history of tick bite . Serologic testing remains unreliable . Oral or parenteral antibiotics remain the mainstay of treatment . Chronic arthritis develops in approximately 10% of patients with Stage III disease . Lyme arthritis must be considered in the differential diagnosis of patients with mono- or oligoarticular joint involvement, especially in children and young adults with possible tick exposure . Further advances in antimicrobial therapy and serologic testing are anticipatedPublication Types:

	Review
	Review, Tutorial

What Is Growth Medium?, What Is Prokaryote?, What Is Genetic Engineering?, What Is MIC?, What Is Dna?, c, Microbe, a, Microbes, n, Bacterium, a, Microorganisms, e, Bacteria, c, Shigella, i, Haemophilus, e, Denitrificans, i, Bacillus, n, Pasteurella, n, Antibiotic treatment, s, Staphylococcus, a, Escherichia coli, o, Bactericidal, c, Antibiotics, c, Agrobacterium, r, Bacillus, r, Staphylococcus aureus, r, Escherichia coli, a, Microbial, e, Denitrifying, a, Brevibacteria, n, Fermentations, s, Multidrug resistant, c, Antimicrobials, o, Antimicrobials

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

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

Last modified: May 25, 2005