Bactericidal

Infection, 1994 May-Jun, 22(3), 160 - 4
Kinetics and correlation with body temperature of circulating interleukin-6, interleukin-8, tumor necrosis factor alpha and interleukin-1 beta in patients with fever and neutropenia; Engel A et al.; Interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF) are important mediators of fever and inflammation, and are involved in the pathogenesis of sepsis . There is only limited data on serum concentrations of these proinflammatory cytokines in patients with fever and neutropenia, and their interrelationship and correlation with body temperature and clinical disease early in the febrile response during neutropenia have not been studied . Immunoreactive TNF, IL-1 beta, IL-6, and IL-8 in serum samples serially obtained from 14 adult patients with neutropenia and fever considered or documented to be due to infection were measured . IL-6 and Il-8 were consistently elevated in all patients, and correlated well with each other and with body temperature . Median peak concentration of IL-6 and IL-8 were 400 pg/ml (range: 100 to 41,000 pg/ml), and 1,025 pg/ml (range: 600 to 26,000 pg/ml), respectively, and levels of both cytokines rapidly declined in patients responding to antimicrobial therapy . Despite frequent sampling before and after the temperature peaks TNF and IL-1 beta, conversely, were less frequently detectable, with median peak values of < 10 pg/ml (range: < 10 to 150 pg/ml) for TNF, and 17 pg/ml (range: < 10 to 36 pg/ml) for IL-1 beta, respectively . The role of neutro- and monocytopenia with depletion of important cytokine producing and target cells in this particular cytokine response pattern needs to be further studied.

Biol Pharm Bull, 1994 May, 17(5), 654 - 7
DNA strand-breaking activities of quinolone antimicrobial agents under visible light irradiation; Iwamoto Y et al.; The DNA strand-breaking activities of 9 quinolones, widely used as antimicrobial agents and suspected to induce photo-dermatological disorders in humans, were examined under irradiation using standard domestic fluorescent lamps . Two quinolones, tosufloxacin and enoxacin, converted the supercoiled covalently closed circular plasmid DNA to the open circular form under visible light irradiation . The maximum of photodynamic single strand-breaking activity for tosufloxacin was found to be 12% at 50 microM and that of enoxacin was 33% at a concentration of 2 mM . The DNA strand-breaking activities of photoirradiated tosufloxacin and enoxacin were markedly inhibited by NaN3 but only partially by D-mannitol, superoxide dismutase (SOD) and catalase did not inhibit these activities . These results suggest that some quinolone antimicrobial agents can be activated by visible light and induce phototoxic DNA damage in various organisms . We should carefully investigate such phototoxic activities during the development of new quinolones to avoid producing phototoxic disorders in man.

Pediatr Infect Dis J, 1994 May, 13(5), 386 - 93
Investigation of an epidemic of invasive aspergillosis: utility of molecular typing with the use of random amplified polymorphic DNA probes; Buffington J et al.; When seven immunocompromised patients developed invasive aspergillosis during construction at a hospital, new methods were performed to compare fungal isolates and a case-control study was conducted to determine risks for infection . Typing of Aspergillus flavus with the use of restriction endonuclease analysis and restriction fragment length polymorphism using random amplified polymorphic DNA reactions to generate DNA probes revealed different patterns between isolates from two patients and a similar pattern among those from one patient, a health care worker, and an environmental source . Case patients were more likely than controls to have longer periods of hospitalization (median, 83 vs . 24 days; P < 0.01), neutropenia (median, 33 vs . 6 days; P < 0.05), and exposure to broad spectrum antimicrobials (median, 56 vs . 15 days; P = 0.08) . No patients restricted to protected areas developed aspergillosis . Risk of exposure of immunocompromised patients to opportunistic organisms stirred up by construction activity may be decreased by admitting these patients to protected areas away from construction activity and by restricting traffic from construction sites to these areas . Although typing of A . flavus isolates did not reveal a single type or source of organism responsible for infection, this method may facilitate epidemiologic investigation of possible nosocomial sources and transmission in similar settings.

Rev Rhum Ed Fr, 1994 May, 61(5), 343 - 7
{Does septic arthritis occur in human immunodeficiency virus infection?}; Saraux A et al.; No prospective, longitudinal, cohort studies comparing septic arthritis in HIV-positive and HIV-negative individuals belonging to the various risk factor groups for HIV-infection are available . However, a review of the literature provided information on the main features of pyarthrosis in HIV-infected patients . The clinical and microbiological characteristics, as well as the outcome of this rare complication, vary with the risk factor group and with the severity of the immune deficiency . Pyogenic bacteria are the most common causative agents and should be looked for routinely since they usually respond well to antimicrobial therapy.

Stem Cells, 1994 May, 12(3), 322 - 8
In vivo stimulation of neutrophil function by lenograstim (glycosylated rHuG-CSF) in oncohematologic patients: results of a phase I trial; Fossat C et al.; The aim of this work was to study the evolution of neutrophil functions in non-neutropenic cancer patients . Thirty non-neutropenic patients, median age 35 years (range 19-52), with solid tumors (n = 21) or lymphomas (n = 9) entered a phase I study of five days of s.c . (n = 24) or i.v . bolus (n = 6) lenograstim, recombinant human glycosylated granulocyte colony-stimulating factor (rHuG-CSF Chugai-Rhone-Poulenc), with dose escalation from 1 to 40 micrograms/kg/day . Neutrophil functions were studied before lenograstim (D1) and 24 h after the last dose (D6) . Granulocyte count rose in a significant way, and enzyme release, phagocytosis and bacterial killing were stimulated . All patients had improvement of at least one neutrophil function . Directed migration was depressed, although it was still in the normal range . These findings confirm that lenograstim is a potent activator of neutrophil functions in non-neutropenic cancer patients and may be useful as an adjunct to conventional antimicrobial therapy.

Chemotherapy, 1994 May-Jun, 40(3), 215 - 20
Effect of antibiotics on Bordetella pertussis adhering activity: hypothesis regarding mechanism of action; Scaglione F et al.; Microbial adherence to epithelial cell surfaces has been implicated as the first step in the initiation of several infectious diseases . The ability of antibiotics to affect the properties of bacterial adherence to cell surfaces may be a criterion in selecting antibiotics for therapy . This study was performed in order to investigate the activity of amoxicillin, chloramphenicol, and clarithromycin in modifying the adhering activity of Bordetella pertussis to human epithelial cells . The actions of antibiotics, alone or combined with aprotinin, were compared with that of trypsin, aprotinin and trypsin+aprotinin, to investigate the chemical nature of the ligand where antibiotics could act . The adhering activity was evaluated on human epithelial cells, collected from the oral mucosa, challenged with B . pertussis A2963 previously incubated in the presence of the tested substances for 1 h at 37 degrees C in a shaker incubator . After staining, the percentage of mucosal cells with more than 50 adhering bacteria was evaluated . Under the described experimental conditions, trypsin significantly reduced the adherence of B . pertussis . Aprotinin had no effect but was able to counteract the inhibitory action of trypsin . Both clarithromycin and chloramphenicol markedly reduced adhering activity and their actions were not counteracted by aprotinin . Amoxicillin was without effect . It was hypothesized that chloramphenicol and clarithromycin, exerting their antimicrobial action by inhibiting bacterial protein synthesis, affected bacterial adhesion through an unknown mechanism without proteolytic effect.

Fed Regist, 1994 May 17, 59(94), 25758 - 63
Preventing the Spread of Vancomycin Resistance--A Report from the Hospital Infection Control Practices Advisory Committee prepared by the Subcommittee on Prevention and Control of Antimicrobial-Resistant Microorganisms in Hospitals; comment period and public meeting--CDC . Notice; Simultaneous determination of primaquine and carboxyprimaquine in plasma using high-performance liquid chromatography with electrochemical detection; Department of Pathology and Laboratory Medicine, School of Medicine, Indiana University, IndianapolisA selective and sensitive high-performance liquid chromatographic method with electrochemical detection is described for the simultaneous quantitation of primaquine and carboxyprimaquine, its primary metabolite, in plasma . After addition of internal standard, plasma was deproteinized by addition of acetonitrile . Nitrogen-dried supernatants, resuspended in mobile phase were analyzed on a C8 reversed-phase column . Limits of detection for primaquine and carboxyprimaquine were 2 and 5 ng/ml with quantitation limits of 5 and 20 ng/ml, respectively . None of 47 tested antimicrobial agents interfered . In contrast to previously reported methods, the assay sensitivity and specificity are sufficient to permit quantitation of primaquine in plasma for pharmacokinetics following low dose (30 mg, base) oral administration of primaquine, typically used in the treatment of malaria and Pneumocystis carinii pneumonia.

Biochemistry, 1994 Apr 19, 33(15), 4562 - 70
Magainin oligomers reversibly dissipate delta microH+ in cytochrome oxidase liposomes; Juretic D et al.; Magainin peptides present in the skin of Xenopus laevis and identified as antimicrobial agents are shown to decrease the membrane potential in cytochrome oxidase liposomes . They also released respiratory control with a third or higher order concentration dependence . Respiratory control was restored by proteolytic digestion of the added magainin . The amount of magainin required for half-maximal stimulation of respiration was proportional to lipid concentration . At appreciably higher concentrations magainins inhibited uncoupled respiration . The results are discussed in terms of a model in which most of the added magainin adsorbs as a monomer to the membranes but equilibrates with a multimeric pore that causes rather general permeability of membranes . The ensuing ion permeation dissipates membrane potential and stimulates respiration.

Cas Lek Cesk, 1994 Apr 18, 133(8), 235 - 6
{Endocrinology 1992-1993}; Schreiber V; In a brief review of advances made in endocrinology during the past two years, focused on steroid hormones, the author discusses findings on mineral corticoid and glucocorticoid receptors and their interaction with hormone responsive elements in nuclei of target cells . The antimicrobial action of some steroid hormones and general characteristics of the cell reaction to stress (proteins of heat shock) are also new findings . In the region of peptide hormones the author mentions findings pertaining to the mechanisms of development of adenohypophyseal adenomas, probably by the action of GHRH . It is assumed that some derivatives of prostaglandins will have an antiviral and anti-tumorous effect . An endogenous ligand for tetra-hydro-cannabinol receptors was isolated . Preventive administration of insulin protects relatives of patients with diabetes mellitus type I from the development of the disease.

Ann N Y Acad Sci, 1994 Apr 15, 712, 102 - 16
Role of hemocyte-derived granular components in invertebrate defense; Iwanaga S et al.; Figure 2 illustrates an outline of the cellular and humoral defense systems in limulus . On the basis of the knowledge described above, it is suggested that granular components present in L and S granules in the hemocytes play a decisive role in the biological defense for this animal . The isolated L granules contain at least three clotting factors plus coagulogen as the major component . The known anti-LPS factor and a number of additional unknown protein components are also present in the L granules . On the other hand, the isolated S granules contain antimicrobial tachyplesins as the major component, in addition to six unidentified proteins . We speculate that the L-granule-derived protein components, which probably contain all the factors essential for the Limulus clotting system participate, in immobilizing invading microbes, and that the S-granule-derived tachyplesins contribute to a self-defense system against invaders . Although we have not mentioned hemolymph plasma components, there are many humoral factors, such as proteinase inhibitors, alpha 2-macroglobulin, various lectins, C-reactive protein, and polyphemin, all of which are important for antimicrobial defense . Furthermore, Liu and colleagues have reported several endotoxin-binding proteins and a cell-adhesion protein found in the Limulus hemocytes . Although the exact functions of these substances are unknown, they may act in concert with other components to provide biological defense for the animal . Nevertheless, compared to our knowledge of mammalian blood cells, much less remains to be learned of biological/physiological events in horseshoe crab hemocytes.

J Immunol, 1994 Apr 15, 152(8), 4080 - 6
Lipopolysaccharide and cytokine augmentation of human monocyte IgA receptor expression and function; Shen L et al.; Receptors for IgA (Fc alpha R) are found on phagocytic cells in the peripheral blood and tissues associated with mucosal areas where IgA Abs constitute a major line of defense . Because Fc alpha R are capable of triggering protective functions of monocytes and neutrophils, such as phagocytosis and the oxidative burst, they may be important in amplifying the antimicrobial effects of IgA . Various cytokines play a role in regulating function and FcR expression of monocytes, macrophages, and neutrophils . The present studies examine the modulation of monocyte Fc alpha R by LPS and cytokines . LPS strongly up-regulated monocyte Fc alpha R expression . TNF and IL-1, produced in response to LPS, promoted Fc alpha R increase, as did GM-CSF; whereas IFN-gamma down-regulated Fc alpha R . Increased receptor expression was accompanied by augmented IgA-mediated phagocytosis . An increase in Fc alpha R-specific mRNA was detected in monocytes treated with TNF, IL-1, GM-CSF, and LPS; whereas message was reduced in cells treated with IFN-gamma . Monocyte-derived macrophages and cells of the Monomac 6 monocyte-like line expressed greater numbers of Fc alpha R than monocytes but were less responsive to LPS and TNF . Cell lines THP-1 and U937, which expressed similar or lower levels of Fc alpha R than monocytes, displayed an increase in Fc alpha R in response to LPS and, to various degrees, to TNF, IL-1, and GM-CSF . These results indicate that Fc alpha R on monocytes are modulated by endotoxin and an array of cytokines distinct from those that regulate expression of FcR for IgG.

FEBS Lett, 1994 Apr 11, 342(3), 281 - 5
Gallinacins: cysteine-rich antimicrobial peptides of chicken leukocytes; Harwig SS et al.; We purified three homologous antimicrobial peptides ('gallinacins') from chicken leukocytes, examined their antimicrobial activity in vitro, and established their primary sequences by a combination of gas phase microsequencing and on-line LC-ESI-MS analysis of endo- and exoprotease peptide digests . The peptides contained 36-39 amino acid residues, were relatively cationic due to their numerous lysine and arginine residues, and each contained 3 intramolecular cystine disulfide bonds . Gallinacins showed primary sequence homology to the recently delineated beta-defensin family, heretofore found only in the respiratory epithelial cells and neutrophils of cattle, suggesting that beta-defensins originated at least 250 million years ago, before avian and mammalian lineages diverged . The 9 invariant residues (6 cysteines, 2 glycines and 1 proline) common to avian gallinacins and bovine beta-defensins are likely to constitute the essential primary structural motif of this ancient family of host-defense peptides.

J Biol Chem, 1994 Apr 8, 269(14), 10849 - 55
Ranalexin . A novel antimicrobial peptide from bullfrog (Rana catesbeiana) skin, structurally related to the bacterial antibiotic, polymyxin; Clark DP et al.; Antimicrobial peptides comprise a diverse class of molecules used in host defense by plants, insects, and animals . In this study we have isolated a novel antimicrobial peptide from the skin of the bullfrog, Rana catesbeiana . This 20 amino acid peptide, which we have termed Ranalexin, has the amino acid sequence: NH2-Phe-Leu-Gly-Gly-Leu-Ile-Lys-Ile-Val-Pro-Ala-Met-Ile-Cys-Ala-Val-Thr- Lys-Lys - Cys-COOH, and it contains a single intramolecular disulfide bond which forms a heptapeptide ring within the molecule . Structurally, Ranalexin resembles the bacterial antibiotic, polymyxin, which contains a similar heptapeptide ring . We have also cloned the cDNA for Ranalexin from a metamorphic R . catesbeiana tadpole cDNA library . Based on the cDNA sequence, it appears that Ranalexin is initially synthesized as a propeptide with a putative signal sequence and an acidic amino acid-rich region at its amino-terminal end . Interestingly, the putative signal sequence of the Ranalexin cDNA is strikingly similar to the signal sequence of opioid peptide precursors isolated from the skin of the South American frogs Phyllomedusa sauvagei and Phyllomedusa bicolor . Northern blot analysis and in situ hybridization experiments demonstrated that Ranalexin mRNA is first expressed in R . catesbeiana skin at metamorphosis and continues to be expressed into adulthood.

Br J Surg, 1994 Apr, 81(4), 557 - 60
Effects of minimally invasive surgery on hypochlorous acid production by neutrophils; Carey PD et al.; The production of chlorinated oxidants such as hypochlorous acid is a central antimicrobial and immunoregulatory function of neutrophils . Neutrophil hypochlorous acid production was compared in patients undergoing uncomplicated laparoscopic surgery (group 1) and those submitted to conventional open surgery (group 2) . Preoperative peak hypochlorous acid production was similar in the two groups (mean(s.e.m.) 0.60(0.05) versus 0.69(0.06) nmol/min respectively) . In group 2, mean(s.e.m.) neutrophil hypochlorous acid production fell significantly on day 1 after surgery (0.36(0.05) nmol/min; P < 0.01) but this did not occur in group 1 (0.63(0.07) nmol/min) . By day 6 hypochlorous acid kinetics had returned to preoperative levels in both groups . Minimally invasive surgery is less disruptive of neutrophil function than conventional open procedures.

Arch Pharm (Weinheim), 1994 Apr, 327(4), 211 - 3
Synthesis of new 7-substituted 4-methylcoumarin derivatives of antimicrobial activity; Eid AI et al.; New cyclic derivatives derived from 4-methyl-7-coumarinyloxyacetic acid hydrazide have been synthesized . Some representative examples were screened for antimicrobial activity.

Pharmazie, 1994 Apr, 49(4), 279 - 81
Antimicrobial and antitumoral activities of 6-allyl-5,6-dihydro-5-hydroxypyran-2-one, a lactone produced by a new Drechslera species; Guiraud P et al.; Antifungal, antibacterial and antitumoral properties of 6-allyl-5,6-dihydro-5-hydroxypyran-2-one were researched . This compound was isolated from culture medium of a new Drechslera species from the area of the Dead Sea . The product exhibited a large activity spectrum against microorganisms, with interesting IC 50 values close to those obtained with reference compounds (kanamycin and ketoconazole) . Antitumoral potentiality was 10 to 58 times less important than with doxorubicin, however IC 50 obtained were below 4 micrograms/ml, which is the threshold value proposed by National Cancer Institute for preliminary screening of active molecules.

Am J Hematol, 1994 Apr, 45(4), 325 - 9
Disseminated Mycobacterium avium-intracellulare infection in a patient with myelodysplastic syndrome (refractory anemia); Tsukada H et al.; A 31-year-old woman presented with fever and arthralgia . Despite treatment with antimicrobials and corticosteroids, her symptoms persisted . A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8 . Cultures of bone marrow, blood, and gastric juice showed Mycobacterium avium-intracellulare (MAI) . She was treated with antimycobacterial drugs and recombinant human G-CSF/M-CSF and showed an initial response, but spike fever recurred and pancytopenia progressed . Hepatosplenomegaly and marked retroperitoneal lymphadenopathy were revealed, indicating further dissemination of MAI . Treatment with recombinant human GM-CSF and very-low-dose cytosine arabinoside, was started but was not effective . This case showed significant reduction in peripheral blood T-lymphocytes, especially the CD4+ population, and low immunoglobulin levels . Immunodeficiency state associated with long-term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI.

J Trop Med Hyg, 1994 Apr, 97(2), 108 - 12
The pattern and outcome of burn injuries at Wesley Guild Hospital, Ilesha, Nigeria: a review of 156 cases; Adesunkanmi K et al.; A review of 156 patients with burn injuries admitted over a 5-year period (January 1988-December 1992) at Wesley Guild Hospital, Ilesha, was undertaken . The male:female ratio was 1.6:1 . About 70% of the cases were between 1 and 10 years of age (mean 9 years) . Scalds were responsible for 50.6% of the cases while naked flames, including kerosene explosion and burns at road traffic accidents, were responsible for 43.5% . Seventy-one per cent were due to domestic accidents . The burns were categorized as major in 70% of cases . The trunk accounted for 56.4% of anatomical areas involved, upper limbs 51.3%, lower limbs 48%, while head and neck accounted for 28.8% . Open dressings were used in 70.5% of the cases, combined open and closed dressings in 22.4% and closed dressings in 10.3% . In about 90% of cases, silver sulphadiazine was used as a topical antimicrobial agent while natural honey was used on the rest . Wound infection was the commonest complication occurring in 24.4%, while mortality was recorded in 7.7% of cases.

Am J Trop Med Hyg, 1994 Apr, 50(4), 440 - 7
Secretion of an inducible cecropin-like activity by cultured mosquito cells; Hernandez VP et al.; Characterization of activities that provide potential targets for genetic manipulation of pathogen development, maintenance, and transmission in transgenic insects has applications to the eventual control of malaria and other arthropod-transmitted diseases . We have identified inducible activities from cultured mosquito (Aedes albopictus) cells, including one that shares the antimicrobial properties of cecropins from other insects . The cecropin-like activity can be induced by treatment with heat-killed Escherichia coli, is secreted into the cell culture medium, and can be detected after electrophoresis of acid-precipitable proteins on polyacrylamide gels at pH 4.3 . Cecropin lacks the amino acids methionine and cysteine . Other proteins secreted in response to bacterial induction measure 111, 66, 53, and 32 kD; these proteins incorporate sulfur-containing amino acids and were detected on denaturing polyacrylamide gels . The synthesis of antimicrobial proteins by mosquito cells in culture will contribute to an understanding of the diversity of molecules that participate in insect immunity and to the use of continuous cell lines and their inducible products to explore and manipulate regulation of physiological processes relevant to vector biology.

J Fam Pract, 1994 Apr, 38(4), 353 - 7
Management of upper respiratory tract infections in Dutch family practice; de Melker RA et al.; BACKGROUND . Family physicians vary in their management of upper respiratory tract infections (URTIs), especially regarding prescription of antimicrobial drugs and patient referral . This study was designed to provide insight into this variation in the management of URTI . METHODS . A secondary data analysis of a nationwide study of morbidity and interventions regarding the management of cases of acute otitis media, otitis media with effusion, acute upper respiratory tract infections (acute URTIs), sinusitis, and acute tonsillitis was performed . One hundred sixty-one Dutch family physicians and 335,000 patients were included in the study . RESULTS . About 10% of all first contacts in this study were house calls, which are most often made to patients in the youngest and oldest age categories . In one third of all first contacts, an antimicrobial drug was prescribed, most frequently for sinusitis (72%) and acute tonsillitis (74%), much less frequently for otitis media and acute URTI . Doxycycline and amoxicillin were prescribed most frequently; two thirds of all antimicrobial prescriptions for the first contact were for one of these two drugs . In 1% of all first contacts and 6% of repeat contacts, patients with URTI were referred to a specialist . CONCLUSIONS . Compared with physicians in other countries, Dutch family physicians show a relatively restrictive and selective prescription behavior in dealing with URTI . This may be why the Netherlands has one of the lowest reported levels of antibiotic resistance . House calls are still important in Dutch family practice.

Chest, 1994 Apr, 105(4), 1109 - 15
Identification of low-risk hospitalized patients with pneumonia . Implications for early conversion to oral antimicrobial therapy; Weingarten SR et al.; PURPOSE: Few available data exist to define either the medically necessary duration of parenteral antimicrobial therapy or length of stay for hospitalized patients with pneumonia . Therefore, we investigated the potential safety and effectiveness of a practice guideline recommending early conversion of low-risk patients with pneumonia from parenteral to oral antimicrobial therapy and early hospital discharge . PATIENTS AND METHODS: The practice guideline was studied retrospectively in 503 hospitalized patients with pneumonia at a teaching community hospital . RESULTS: Thirty-three percent of patients with pneumonia were classified as at low risk for complications and potentially suitable for early conversion to oral antimicrobial therapy according to the guideline . Were the guideline to have been used to guide patient discharge decisions, 619 additional bed-days would have been made available to accommodate incoming patients . A consensus among physician reviewers led to the judgment that quality of care would not have worsened for 98.2 percent of low-risk patients had they been switched to oral antimicrobial therapy on the third hospital day, nor would quality of care have been worsened for 93.4 percent of low-risk patients had they been discharged on the fourth hospital day . CONCLUSION: The practice guideline that we studied has the potential to safely reduce the duration of parenteral antimicrobial therapy and length of hospital stay for selected low-risk patients with pneumonia . The guideline should be studied in a prospective clinical trial.

J Surg Res, 1994 Apr, 56(4), 378 - 84
Cytoprotection of human dermal fibroblasts against silver sulfadiazine using recombinant growth factors; McCauley RL et al.; Topical antimicrobial agents, silver sulfadiazine (SSD) and mafenide acetate (MA), have been associated with delayed wound healing . Previous in vitro studies with human dermal fibroblasts (HDF) have shown progressive cellular cytotoxicity with increasing concentrations of SSD and MA . However, preexposure of HDF to epidermal growth factor, basic fibroblast growth factor, or platelet-derived growth factor has resulted in cytoprotection of HDF against 0.01 and 0.03% concentrations of SSD as determined by phase-contrast microscopy (PCM), hemocytometer cell counts, and total cellular protein content . PCM, however, showed slower destruction of HDF at the 0.05% concentration of SSD . These data suggest that cells activated by growth factors either take up less SSD or are more resistant to the direct cytotoxic effects of this drug.

Infect Immun, 1994 Apr, 62(4), 1236 - 40
Lactoferrin binds to porins OmpF and OmpC in Escherichia coli; Erdei J et al.; Lactoferrin (Lf) is an iron-binding antimicrobial protein present in milk and on mucosal surfaces, with a suggested role in preimmune host defense . Certain strains of Escherichia coli (bacterial whole cells) demonstrate specific interaction with 125I-labeled Lf . A band with a mass of approximately 37 kDa, which was reactive with horseradish peroxidase-labeled Lf, was identified in the boiled cell envelope and outer membrane preparations of an Lf-binding E . coli strain, E34663, and a non-Lf-binding strain, HH45, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting (immunoblotting) . Such a band was not detected in the unboiled native cell envelope and outer membrane preparations . The molecular mass and the property of heat modifiability suggested that the Lf-binding proteins were porins . The native trimeric form of porin OmpF isolated from strain B6 and its dissociated monomeric form both reacted with horseradish peroxidase-labeled Lf and with monoclonal antibodies specific for OmpF . Furthermore, by using E . coli constructs with defined porin phenotypes, OmpF and OmpC were identified as the Lf-binding proteins by urea-SDS-PAGE and Western blotting and by 125I-Lf binding studies with intact bacteria . These data establish that Lf binds to porins, a class of well-conserved molecules common in E . coli and many other gram-negative bacteria . However, in certain strains of E . coli these pore-forming proteins are shielded from Lf interaction.

J Urol, 1994 Apr, 151(4), 847 - 51
Presentation, diagnosis and treatment of renal abscesses: 1972-1988; Fowler JE Jr et al.; We reviewed 61 consecutive patients with renal abscesses who were treated between 1972 and 1988 to determine whether the patient characteristics and mortality differed from those of patients treated during the preceding 2 decades . The results demonstrate that the predisposing conditions, symptomatology, abnormal physical findings, abnormal laboratory results, abnormal radiographic findings and infecting organisms of patients with renal abscesses have not changed during the last 40 years . Ultrasonography and computerized tomography, which became available in the 1970s, identified 35 of 38 (92%) and 23 of 24 (96%) abscesses, respectively . In 57 cases (97%) the abscess was drained and the patients survived . In 4 cases the abscess escaped clinical detection and contributed to patient death . The marked improvement of survival among patients with renal abscesses during the last 2 decades is attributable to improved diagnostic precision and, probably, improved antimicrobial therapy and supportive care.

Rozhl Chir, 1994 Apr, 73(3), 129 - 32
{Use of 3rd generation cephalosporins in antimicrobial prophylaxis in surgery}; Vyhnanek F et al.; In a general and special review the authors discuss contemporary possibilities of antimicrobial prophylaxis in surgery focused on cephalosporins of the third generation . According to available data on the incidence of resistance, pharmacokinetics and others the most suitable preparations seem to be cefotaxime and ceftriaxone . They are used in particular in thoracic surgery, hepatobiliary surgery, colorectal surgery and urology.

Rozhl Chir, 1994 Apr, 73(3), 103 - 5
{Foil bandages--a modern method of covering wounds}; Sedlarik KM et al.; Single-layer foil bandages which belong to the group of so-called occlusive bandaging materials were originally developed from incision foils . Due to their semipermeability theses bandages permit only restricted evaporation of water from the wound and thus maintain its surface constantly slightly wet . They can be used for longer periods and are thus more economical . Although foil bandages are suitable only for some types of wounds, they have great advantages . Wounds dressed with these foil bandages can be easily and frequently checked and offer wounds excellent antimicrobial protection.

Minerva Pediatr, 1994 Apr, 46(4), 157 - 60
Successful interferon gamma therapy in a patient with X-linked chronic granulomatous disease, McLeod syndrome and hyper-IgE . Case report; Kantar A et al.; Recent studies have shown clinical benefit resulting from recombinant interferon gamma (rIFN-gamma) therapy in patients affected by chronic granulomatous disease (CGD), which represents an important adjunct to conventional therapy . In order to evaluate the effect of interferon gamma therapy, we investigated clinical and haematological parameters in a child with X-linked CGD, McLeod phenotype (kell negative) and hyper-IgE, before and after 8 months of therapy . Our results show no significant effect of rIFN-gamma on the respiratory burst of peripheral polymorphonuclear leukocytes . This notwithstanding, we observed improved clinical and haematological conditions . These results support the view that interferon gamma may benefit these subjects by influencing oxygen-independent antimicrobial activity or other immunological parameters.

J Ethnopharmacol, 1994 Apr, 42(2), 95 - 9
Antimicrobial constituents of Rhus glabra; Saxena G et al.; The antimicrobial activity of the methanol extract and isolated constituents of Rhus glabra (Anacardiaceae), a species used in folk medicine by North American native people, was evaluated against 11 microorganisms, including gram-positive and gram-negative bacteria . The extract was subsequently fractionated and monitored by bioassays leading to the isolation of three antibacterial compounds, the methyl ester of 3,4,5-trihydroxybenzoic acid (methyl gallate) (minimal inhibition concentration (MIC) 12.5 micrograms/ml), 4-methoxy-3,5-dihydroxybenzoic acid (MIC 25 micrograms/ml) and gallic acid (MIC > 1000 micrograms/ml) . The first two compounds are reported here for the first time from Rhus glabra . Their structures were established using spectroscopic and chemical methods.

Int Dent J, 1994 Apr, 44(2), 181 - 9
Bactericidal effect of laser light and its potential use in the treatment of plaque-related diseases; Wilson M; Chemical antibacterial agents are increasingly being used in prophylactic and therapeutic regimes for plaque-related diseases . As these agents can be rendered ineffective by the development of resistance in the target organisms there is a need to develop alternative antimicrobial approaches . Light from high-power lasers is known to be bactericidal and investigations have shown that it is effective against organisms implicated in caries and inflammatory periodontal diseases . However, the adverse effects of such light on dental hard tissues argue against its use solely as an antibacterial agent . Although light from low-power lasers has no adverse effect on bacterial viability, bacteria can be sensitised to killing by such light by prior treatment with a chemical photosensitising agent . Lethal photosensitisation of a wide range of cariogenic and periodontopathogenic bacteria has been demonstrated using light from a helium/neon or gallium aluminium arsenide laser in conjunction with a dye such as toluidine blue or aluminium disulphonated phthalocyanine as a photosensitiser . The advantages of the technique are that killing is achieved in very short periods of time (< 60 s), resistance development in the target bacteria would be unlikely and damage to adjacent host tissues can be avoided . This approach may be a useful alternative to antibiotics and antiseptics in eliminating cariogenic and periodontopathogenic bacteria from disease lesions.

J Antimicrob Chemother, 1994 Apr, 33(4), 721 - 8
Loss of bactericidal activities of quinolones during the post-antibiotic effect induced by rifampicin; Meng X et al.; The post-antibiotic effect (PAE) is the phenomenon of persisting suppression of bacterial growth as a result of prior antimicrobial exposure . In antimicrobial therapy, multiple doses of either a single drug or a combination of drugs are common . Accordingly, the following question may arise: what impact might the PAE induced by the previous dose impose on the subsequent bactericidal action of a cycle-specific antibiotic . To answer the question, a study was conducted using pefloxacin, norfloxacin, ciprofloxacin and ofloxacin as test drugs, rifampicin as the PAE inducer and Escherichia coli ATCC 25922 as the test organism . Bacterial kill kinetics were determined for each quinolone at 4 x MIC before rifampicin treatment and during the PAE period following rifampicin challenge . The relative bactericidal activity of the quinolones during the PAE period was calculated . During the PAE period, pefloxacin, norfloxacin, ciprofloxacin and ofloxacin displayed only 6%, 8%, 7% and 33% of their normal activities, respectively . The results were compared to those obtained at low temperature (4 degrees C) and when the cells were challenged simultaneously with a quinolone and with rifampicin . The findings of this study suggest that prolonging the dosing interval by taking the PAE into account may not only lower the cost of antimicrobial therapy and the risk of toxicity, but also ensure the efficacy of subsequent doses.

J Pharm Sci, 1994 Apr, 83(4), 545 - 8
Antimicrobial evaluation of some styryl ketone derivatives and related thiol adducts; Erciyas E et al.; Acyclic alpha,beta-unsaturated ketones were synthesized and treated with either 2-mercaptoethanol or cystenamine hydrochloride under the simulated physiological conditions . The thiol group of these model biological nucleophiles underwent Michael type addition to the activated double bond . The incubation of the bis-Mannich base of 3-benzylidene-2,4-pentanedione with 2-mercaptoethanol, surprisingly, gave rise to the formation of 5-{(2-hydroxyethyl)thio}-1-phenyl-1- penten-3-one (8) in low yield . Evaluation of the compounds versus Gram-positive and Gram-negative bacteria and also a type of fungus indicated that the conjugated ketones and their adducts, except the bis-Mannich base, have antimicrobial activity at 10 micrograms/mL . The Mannich base, 3, showed antibacterial property against only Escherichia coli at 1000 micrograms/mL in spite of containing a bioactive styryl ketone structure and having deamination ability . However, the thiol adducts, which do not contain any alpha,beta-unsaturated ketone function, exhibited similar antimicrobial potency to the conjugated ketone derivatives, possibly due to the exchange reaction with enzymes or coenzymes in the microorganisms.

J Pharm Sci, 1994 Apr, 83(4), 463 - 7
Photodegradation of some quinolones used as antimicrobial therapeutics; Tiefenbacher EM et al.; The photostability of the fluoroquinolones ciprofloxacin (CPX), ofloxacin (OFX), and fleroxacin (FLX) toward ultraviolet irradiation (UVA) and room light was investigated in dilute aqueous solutions . A series of photoproducts was observed by high-performance liquid chromatography (HPLC) for all three drugs . As little as 1 h of exposure to room light was enough for the formation of detectable amounts of CPX photoproducts . The major CPX photoproduct was characterized as a dimer by liquid secondary ion mass spectrometry, but its structure was not determined . Since irradiation of CPX results (as cited in ref/11) in a loss of antibacterial activity and since all substances, parent drugs as well as their photoproducts, are potential candidates for undesired drug effects, quinolone drugs should be strictly protected from all light during storage and administration.

J Fla Med Assoc, 1994 Apr, 81(4), 256 - 60
Systemic toxicity . Associated with topical ophthalmic medications; Flach AJ; Topically administered ophthalmic preparations can be associated with systemic adverse events if excessive absorption occurs . The nasolacrimal system can deliver eyedrops and ointments to the vascular nasal mucosae where the drugs are absorbed avoiding the first-pass effect and reaching sites of action with increased bioavailability . Topical ophthalmic eye-drop preparations most often involved include glaucoma medications, and diagnostic, antimicrobial and anti-inflammatory drugs . This article reviews reported systemic reactions and summarizes methods useful in preventing excessive absorption.

J Natl Med Assoc, 1994 Apr, 86(4), 305 - 10
Microorganisms and psoriasis; Rosenberg EW et al.; It has been suggested previously that psoriasis is best explained as a distinctive inflammatory response to a variety of microbial stimuli, all acting primarily through activation of the alternative complement pathway . For the past several years we have conducted a "Problem Psoriasis Clinic" based on that premise . Patients are questioned, examined, and subjected to microbiologic laboratory investigations in an attempt to identify possibly relevant microorganisms, and then are treated with antibiotics . This article lists the most commonly found microorganisms in psoriasis patients and describes the usual treatment for each . Results obtained with this approach compare favorably with those achieved with more usual anti-psoriasis treatments . We recommend that a microbiologic investigation and a trial of antimicrobial treatment should precede any plan to treat psoriasis patients with anything more than the simplest topical agents.

Vet Clin North Am Equine Pract, 1994 Apr, 10(1), 87 - 107
Drug therapy in the neonatal foal; Baggot JD; The neonatal period in foals refers to the first 7 days of postnatal life . The effects of drugs (pharmacologic agents) may be different in neonatal foals, particularly during the first 3 days of postnatal life, from those in older foals and adult horses . The changed drug effects decrease as the physiologic processes that affect absorption, distribution, and elimination (metabolism and excretion) of drugs mature . Dosage regimens should take into account the altered pharmacokinetic profiles of drugs, and because of wide individual variation, the response to therapy should be closely monitored for signs of toxicity . In conjunction with the prudent use of drugs, good nursing care and the provision of supportive therapy are critical in the management of neonatal foal diseases . Over-crowding imposes stress upon young foals and predisposes them to an increased incidence of bacterial and parasitic infections . The collection of specimens for precise microbiologic diagnosis and correction of deficits in serum immunoglobulins should precede antimicrobial therapy . Although E . coli is by far the most common cause of bacterial infections in neonatal foals, other bacterial pathogens of unpredictable susceptibility often cause infection . The selection of an antimicrobial drug for specific therapy should be based on both the microbiologic (quantitative susceptibility) and pharmacologic (pharmacokinetic) properties of the drug . The use of an antimicrobial drug or combination of drugs that will produce a bactericidal effect is highly desirable . Whenever possible, a parenteral preparation that can be administered intravenously should be chosen . The bioavailability and selectivity of action of pharmacologic agents are influenced by the dosage form and route of administration . Diazepam is the sedative drug of choice for neonatal foals . Cimetidine, an H2-receptor antagonist, may be indicated in foals diagnosed to have gastric ulcers; hepatic microsomal oxidative metabolism of drugs administered concurrently with cimetidine is decreased . Nonsteroidal anti-inflammatory drugs (flunixin, phenylbutazone) have a higher incidence of toxicity in foals and, when indicated, should be used at lower dosage than in adult horses . Even though it is highly important to maintain hydration status and electrolyte balance, intravenous infusion should always be performed slowly . Immature renal function decreases the ability of the neonatal animal to excrete excess fluid . The use of drugs in neonatal foals requires greater precision in dosage, more attention to the route and rate of administration, and close monitoring of pharmacologic effects.

Ann Pharmacother, 1994 Apr, 28(4), 515 - 22
Risk factors for acute renal insufficiency in patients with suspected or documented bacterial pneumonia; Welage LS et al.; OBJECTIVE: To describe the incidence of acute renal insufficiency and identify potential risk factors associated with this adverse medical event . DESIGN: A cohort analytic study of patients with documented or suspected bacterial pneumonia . SETTING: Nationwide survey of 74 acute care hospitals across the US . INCLUSION AND EXCLUSION CRITERIA: A total of 1822 adult patients with documented or suspected bacterial pneumonia who were receiving a cephalosporin, penicillin, or an aminoglycoside were enrolled . Patients were excluded if the duration of antimicrobial therapy was < 3 days or if the pneumonia was judged to be nonbacterial . DATA COLLECTION: Clinical pharmacists completed standardized data collection forms on all patients enrolled in the study . Information regarding patient demographics, concurrent illnesses and medications, antibiotic administration, representative laboratory data, and the occurrence of any adverse clinical event was specifically captured . Information regarding the development of acute renal insufficiency was targeted as an event to be captured . MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify significant risk factors for acute renal insufficiency . A subset analysis was similarly performed to identify risk factors associated with aminoglycoside-related acute renal insufficiency . RESULTS: Of the patients enrolled in this study, 8.2 percent developed acute renal insufficiency . Risk factors for acute renal insufficiency included renal disease, aminoglycoside therapy, nosocomial pneumonia, elevated estimated creatinine clearance prior to study entry, cardiac arrest/shock, congestive heart failure, total duration of antibiotics > 7 days, clindamycin therapy, liver disease, and first-generation cephalosporin usage . Risk factors for aminoglycoside-related acute renal insufficiency identified via multiple logistic regression included amphotericin B, congestive heart failure, aminoglycoside trough concentration > 1.5 mg/L, and clindamycin therapy . CONCLUSIONS: The risk factors identified for acute renal insufficiency suggest that severity of illness strongly influences the development of renal insufficiency . Theoretically, the results of this study could serve as a framework for developing risk prevention programs within individual hospitals . Specific risk factors could be identified for a patient population and risk factors that could be modified could then be targeted for intervention . This type of information can also assist clinicians in predicting the probability of the adverse event for a particular patient and subsequently minimizing this risk by initiating intense monitoring or modifying the drug regimen.

Aliment Pharmacol Ther, 1994 Apr, 8(2), 259 - 62
Short report: omeprazole-tetracycline combinations are inadequate as therapy for Helicobacter pylori infection; al-Assi MT et al.; BACKGROUND: Current triple antimicrobial therapies cure Helicobacter pylori infection in 60-90% of cases but are cumbersome . Addition of omeprazole to amoxycillin has been shown to enhance effectiveness when compared to amoxycillin alone . METHOD: We studied omeprazole 20 mg t.d.s . plus tetracycline 500 mg q.d.s . for 14 days (OMP/TCN) and omeprazole 40 mg in the morning plus tetracycline 500 mg q.d.s . along with bismuth subsalicylate tablets 2 q.d.s . (OMP/TCN/BSS) for 14 days . Forty-four patients (19 OMP/TCN, 25 OMP/TCN/BSS) with H . pylori peptic ulcer disease were studied . H . pylori status was evaluated at least 4 weeks after ending antimicrobial therapy . RESULTS: In the OMP/TCN group cure of H . pylori infection was achieved in 5/19 (26%) . Adding bismuth to the regimen improved the results; 4 weeks after ending therapy cure of H . pylori infection was achieved in 12/25 (48%) . CONCLUSIONS: Neither regimen can be recommended for routine cure of H . pylori infection . Although one cannot predict which antimicrobial therapies will be enhanced by the addition of omeprazole, these data suggest that future studies should evaluate drugs whose effectiveness is compromised by low pH.

Antimicrob Agents Chemother, 1994 Apr, 38(4), 886 - 8
Killing acanthamoebae with polyaminopropyl biguanide: quantitation and kinetics; Burger RM et al.; The two Acanthamoeba species most often implicated in corneal keratitis, A . castellanii and A . polyphaga, were exposed as cysts to polyaminopropyl biguanide (PAPB), a commonly used antimicrobial agent . Killing of amoeba cysts was rapid and extensive, with fewer than 2% of either species surviving 30 s of exposure to > or = 45 ppm of PAPB . Killing kinetics were biphasic, and further exposures of 15 min to 1 h killed greater than 90% of those surviving initial killing . This potency of PAPB, together with its low toxicity to humans when ingested or applied topically, underscores the potential of PAPB as an antiamoebic agent.

Antimicrob Agents Chemother, 1994 Apr, 38(4), 830 - 6
Behavior of antibiotics during human necrotizing pancreatitis; Bassi C et al.; The aim of the study was to verify whether antibiotics excreted by the normal pancreas are also excreted in human necrotizing pancreatitis, reaching the tissue sites of the infection . Twelve patients suffering from acute necrotizing pancreatitis were treated with imipenem-cilastatin (0.5 g), mezlocillin (2 g), gentamicin (0.08 g), amikacin (0.5 g), pefloxacin (0.4 g), and metronidazole (0.5 g) . Serum and necrotic samples were collected simultaneously at different time intervals after parenteral drug administration by computed tomography-guided needle aspiration, intraoperatively, and from surgical drainages placed during surgery . Drug concentrations were determined by microbiological and high-performance liquid chromatography assays . All antibiotics reached the necrotic tissues, but with varying degrees of penetration, this being low for aminoglycosides (13%) and high in the case of pefloxacin (89%) and metronidazole (99%) . The concentrations of pefloxacin (13.0 to 23 micrograms/g) and metronidazole (8.4 micrograms/g) in the necrotic samples were distinctly higher than the MICs for the organisms most commonly isolated in this disease; the concentrations in tissue of imipenem (3.35 micrograms/g) and mezlocillin (8.0 and 15.0 micrograms/g) did not always exceed the MICs for 90% of strains tested, whereas the aminoglycoside concentrations in necrotic tissue (0.5 microgram/g) were inadequate . Repeated administration of drugs (for 3, 7, 17, and 20 days) seems to enhance penetration of pefloxacin, imipenem, and metronidazole into necrotic pancreatic tissue . The choice of antibiotics in preventing infected necrosis during necrotizing pancreatitis should be based on their antimicrobial activity, penetration rate, persistence, and therapeutic concentrations in the necrotic pancreatic area . These requisites are provided by pefloxacin and metronidazole and to a variable extent by imipenem and mezlocillin.

Antimicrob Agents Chemother, 1994 Apr, 38(4), 790 - 8
In vitro and in vivo activities of macrolides against Mycoplasma pneumoniae; Ishida K et al.; We investigated the in vitro and in vivo activities of macrolides against Mycoplasma pneumoniae . In vitro MICs of azithromycin, erythromycin, clarithromycin, and roxithromycin were determined . Azithromycin was the most potent antimicrobial agent tested in vitro . Its MIC for 90% of the strains was 0.00024 micrograms/ml . MICs for 90% of the strains of erythromycin, clarithromycin, and roxithromycin were 0.0156, 0.0078, and 0.03125 micrograms/ml, respectively . In vivo activities were assessed in a pulmonary infection model with Syrian golden hamsters . We evaluated the in vivo effects on reduction of viable M . pneumoniae cell counts and on reduction of microscopic and macroscopic histopathologies for azithromycin, erythromycin, and clarithromycin given at 10 mg/kg once daily for 1 and 3 days and given at 15 mg/kg twice daily for 2.5 and 5 days . Azithromycin was significantly more effective than erythromycin or clarithromycin in the same regimens . Especially at 10 mg/kg once daily for 1 day, only azithromycin was significantly effective in the reduction of viable M . pneumoniae cells and histopathologies . These results show that azithromycin is more efficacious than the other drugs tested against M . pneumoniae pneumonia in hamsters . These data suggest that clinical studies of macrolides in human patients are warranted.

J Clin Microbiol, 1994 Apr, 32(4), 1067 - 9
Bacteremia by multidrug-resistant Capnocytophaga sputigena; Gomez-Garces JL et al.; A case of bacteremia caused by a multiresistant strain of Capnocytophaga sputigena in a patient with hematological malignancy is described . The strain presented with a pattern of marked resistance to beta-lactams, with MICs of > 256 mg/liter for ampicillin, ticarcillin, piperacillin, cefazolin, and cefuroxime, 64 mg/liter for cefotaxime, and 32 mg/liter for ceftazidime . In addition, the MIC of ciprofloxacin was 16 mg/liter . Both of these groups of antimicrobial agents are frequently used in the empiric treatment of infections in immunocompromised patients . The appearance of resistant strains suggests the need for antimicrobial susceptibility studies in all patients with severe infections caused by Capnocytophaga spp . or other capnophilic organisms present in the oral microflora of these patients.

Artif Organs, 1994 Apr, 18(4), 266 - 71
New processes for surface treatment of catheters; Sioshansi P; Infection, thrombosis, and stenosis are among the most common complications of blood-contacting catheters and are caused by surface properties of the substrate materials . Ion beam-based processes such as ion implantation and ion beam-assisted deposition affect only the outer micron of the treated material surface; there is little effect on bulk properties . These processes were therefore used on common catheter materials, and their biological properties were evaluated . Ion implantation of materials such as silicone rubber resulted in a less tacky, more wettable surface that demonstrated thrombus-resistance in both in vivo and preliminary clinical studies . Ion beam-assisted deposition was used to deposit silver-based coatings, which demonstrated antimicrobial activity in in vitro and clinical studies . Biocompatibility of these processed catheter materials was also demonstrated using simple laboratory studies . These processes, therefore, can be readily applied to blood-contacting catheters to make them thrombus- and infection-resistant.

Vaccine, 1994 Apr, 12(5), 415 - 8
Vaccination in food animal populations; van Oirschot JT; This report highlights the role of vaccination in the present and future food animal industry in the framework of the disease policy of the European Commission . Vaccination was essential in the virtual eradication of foot-and-mouth disease and classical swine fever, the use of modern marker vaccines opens prospects for eradication of viruses in countries with a high prevalence, and a rebirth of interest in bacterial vaccines is noted, because of the problems of drug resistance and antimicrobial residues . Biotechnology has already led to the development of several new vaccines, and to the improvement of current vaccines, and it still holds great potential for designing basically novel vaccines . Vaccination, thus, is a crucial tool in reducing the enormous economic losses caused by diseases in food animals.

Arzneimittelforschung, 1994 Apr, 44(4), 563 - 5
In vivo susceptibility of Mycobacterium leprae to ofloxacin either singly or in combination with rifampicin and rifabutin . Anti-leprosy activity of ofloxacin and ansamycins in mice; Dhople AM et al.; The antimicrobial effects of ofloxacin against Mycobacterium leprae, either alone or in combination with rifampicin and rifabutin, were studied using mouse foot pad assay technique . When used singly, the minimum concentrations of the drugs needed to completely inhibit the growth of Mycobacterium leprae in foot pads of mice were 50 mg/kg body weight for ofloxacin and 0.003% and 0.0001%, respectively, for rifampicin and rifabutin . However, excellent synergistic effects were observed when mice were fed with 25 mg/kg body weight of ofloxacin along with 0.00003% rifabutin, but not rifampicin . Thus, incorporation of ofloxacin and rifabutin in the multiple drug therapy of leprosy patients is suggested.

Arzneimittelforschung, 1994 Apr, 44(4), 490 - 5
Synthesis and pharmacological evaluation of novel series of sulfonate ester-containing 1,3,4-oxadiazole derivatives with anticipated hypoglycemic activity; Girges MM; Four series of 2,5-disubstituted 1,3,4-oxadiozole derivatives (IV, VII, IX and X) have been synthesized from 4-(4- (Z)-{p- (benzenesulfonyloxy) phenylmethylene}- 5-oxo-1-phenyl-2-imidazolin-1-yl) benzoyl hydrazine derivative (II) with a view to investigate the effect of different structural changes in the oxadiazole moiety on the pharmacological activity of these compounds as possible hypoglycemic agents . The structure of the synthesized compounds was inferred from elemental and spectral data and their hypoglycemic effect, antimicrobial activity and toxicity were evaluated . Twelve of these compounds were effective, when administered at an oral dose of 100 mg/kg, to induce marked reduction in blood glucose level.

Ther Drug Monit, 1994 Apr, 16(2), 209 - 13
Monitoring of pefloxacin serum concentrations in intensive care unit patients: comparison of a new immunoassay with high-performance liquid chromatography; Lacarelle B et al.; Serum quinolone concentrations are not routinely measured in clinical practice . However, in order to optimize quinolone treatment, monitoring of serum concentrations could sometimes be useful particularly in critically ill patients . A new enzyme-linked immunosorbent assay (ELISA) that permits direct determination of pefloxacin in serum is described . To validate this new assay, pefloxacin concentrations were measured in 314 serum samples from 74 intensive care unit patients treated with pefloxacin (400 mg i.v . twice daily) . Reference concentrations were obtained by reverse phase high-performance liquid chromatography (HPLC) with spectrofluorometric detection . Results showed that concentrations measured by ELISA correlated very well with those by HPLC (r = 0.957; y = 1.03 and x -0.15) . In this population, the concentrations found by ELISA varied between individuals (Cmin = 0.70-39 micrograms/ml; Cmax = 5.2-40 micrograms/ml) . However, 86% of the measured Cmax and Cmin levels were adequate for optimal pefloxacin therapy . Only 11% of Cmin and 14% of Cmax were below the optimal values (i.e., 2 and 8 micrograms/ml, respectively) . These results suggest that despite the large therapeutic index of pefloxacin, monitoring of its serum concentrations using a rapid ELISA technique may be useful for optimal antimicrobial treatment of certain intensive care unit patients.

Oral Microbiol Immunol, 1994 Apr, 9(2), 123 - 5
Evaluation of the E test for antimicrobial susceptibility testing of Porphyromonas gingivalis; Pajukanta R et al.; The antimicrobial susceptibilities of 81 recent clinical Porphyromonas gingivalis isolates and two reference strains were determined by the E test, a new method, and were compared with the minimal inhibitory concentrations for these strains obtained by the reference agar dilution method on supplemented Brucella blood agar . The following agreements were obtained: benzylpenicillin 100%, ampicillin 96%, cefaclor 82%, cefuroxime 91%, erythromycin 93%, clindamycin 99%, tetracycline 66%, doxycycline 89%, metronidazole 77% and ciprofloxacin 77% . Very major discrepancies were observed with ciprofloxacin . This study indicates that the E test is an acceptable method to determine the susceptibility of P . gingivalis for most antimicrobials.

Kansenshogaku Zasshi, 1994 Apr, 68(4), 513 - 9
{Effect of biological response modifiers against pulmonary candidiasis in neutropenic mice}; Futenma M et al.; We investigated the prophylactic and therapeutic effects of biological response modifiers (rHG-CSF, M-CSF, rhIL-2) on pulmonary candidiasis in neutropenic mice . Cyclophosphamide treated mice were injected by the intratracheal route with 5 x 10(6) Candida yeast cells . Prophylactic treatment with rhG-CSF afforded significant protection against pulmonary candidiasis in neutropenic mice . Treatment with rhG-CSF also increased the number of peripheral blood neutrophils . The histopathological investigations in our experiments showed that the assembly of PMNs to the infected lung at 24 hrs after bacterial challenge was more remarkable in the rhG-CSF treated mice than that in the vehicle alone . Number of viable candida cells in the infected lung in the rhG-CSF treated mice were significantly decreased . The combination of rhG-CSF and fluconazole was more effective than those of each monotherapy . Prophylactic treatment with M-CSF or rhIL-2 had no influence on pulmonary candidiasis . These results show the possibility that rhG-CSF could be of help for treating human deep candidiasis not successfully treated with antimicrobial agents alone.

Scand J Dent Res, 1994 Apr, 102(2), 120 - 5
Antimicrobial factors, sialic acid, and protein concentration in whole saliva of the elderly; Narhi TO et al.; Concentrations of salivary antimicrobial factors are well documented in children and young adults, but little information is available on such defense factors in healthy elderly persons . We determined the levels of total IgA, total IgG, lysozyme, lactoferrin, myeloperoxidase, salivary peroxidase, amylase, sialic acid, and total protein in a group of 71 subjects aged 76, 81, and 86 yr, as well as their correlations to paraffin-wax-stimulated salivary flow rate . Participants were either unmedicated (n = 67) or using medicines with no oral significance (n = 4) . Statistically significant negative correlations existed between flow rate and total IgA, lysozyme, lactoferrin, sialic acid, and total protein . Concentrations of sialic acid and salivary peroxidase were highest in the oldest age group . Total IgA concentration was higher in women than in men, although men showed higher concentrations of sialic acid and higher sialic acid/total protein ratios . Subjects with poor gingival health had higher concentrations of total protein than did those with no need for periodontal treatment . Edentulous subjects with complete dentures showed significantly lower concentrations of IgG, lactoferrin, and myeloperoxidase than did dentate subjects . Our results suggest that, when compared with data from previous studies, concentrations of salivary antimicrobial agents do not decline with age in unmedicated elderly people . However, defense factors which are derived also from gingival crevicular fluid are decreased in the absence of teeth.

Drugs, 1994 Apr, 47(4), 599 - 610
Use of psychotropic drugs in patients with HIV infection; Ayuso JL; Psychotropic drugs are frequently employed to treat the wide range of neuropsychiatric syndromes that patients infected with the human immunodeficiency virus (HIV) may develop . In order to administer these agents properly, physicians should take certain factors into account: the central nervous systems of these patients are often impaired, the patients tend to suffer from medical illnesses, and they may be taking various other drugs . The possible interactions between substances taken by these patients may sometimes make it necessary to adjust the dosage of psychotropic agents administered . In addition, some of the antimicrobial, antifungal and antiviral agents used in the management of HIV infection may have adverse effects that include neuropsychiatric symptoms . The use of antipsychotic agents in these patients frequently results in the development of extrapyramidal symptoms . Tricyclic antidepressants are not well tolerated by patients with AIDS, due to the anticholinergic effects of these agents . The new antidepressants, which have fewer and milder adverse effects, are safer and have shown their efficacy in the treatment of the depressive episodes often seen in HIV-infected patients . Benzodiazepines must be prescribed with caution in patients with HIV infection and organic brain syndrome, since they can produce amnesia, confusion, lack of inhibition and paradoxical reactions . The indications for the use of psychostimulants in certain clinical situations, such as HIV-associated dementia and depression, is open to debate . Opiates are indicated in pain treatment, and in methadone maintenance programmes . Lithium and carbamazepine are advisable only in very restricted situations.

Plant Mol Biol, 1994 Apr, 25(1), 43 - 57
Triticum aestivum puroindolines, two basic cystine-rich seed proteins: cDNA sequence analysis and developmental gene expression; Gautier MF et al.; From a mid-maturation seed cDNA library we have isolated cDNA clones encoding two Triticum aestivum puroindolines . Puroindoline-a and puroindoline-b, which are 55% similar, are basic, cystine-rich and tryptophan-rich proteins . Puroindolines are synthesized as preproproteins which include N- and C-terminal propeptides which could be involved in their vacuolar localization . The mature proteins have a molecular mass of 13 kDa and a calculated isoelectric point greater than 10 . A notable feature of the primary structure of puroindolines is the presence of a tryptophan-rich domain which also contains basic residues . A similar tryptophan-rich domain was found within an oat seed protein and a mammalian antimicrobial peptide . The ten cysteine residues of puroindolines are organized in a cysteine skeleton which shows similarity to the cysteine skeleton of other wheat seed cystine-rich proteins . Northern blot analysis showed that puroindoline genes are specifically expressed in T . aestivum developing seeds . No puroindoline transcripts as well as no related genes were detected in Triticum durum . The identity of puroindolines to wheat starch-granule associated proteins is discussed as well as the potential role of puroindolines in the plant defence mechanism.

Clin Infect Dis, 1994 Apr, 18 Suppl 3, S227 - 32
Disease due to the Mycobacterium avium complex in patients infected with human immunodeficiency virus: diagnosis and susceptibility testing; Woods GL; Because the symptoms and laboratory abnormalities associated with disseminated disease due to the Mycobacterium avium complex (MAC) are nonspecific, diagnosis requires recovery of the organism from blood or other normally sterile body sites . Isolation of MAC by conventional mycobacterial culture on tubed solid medium generally takes 3-4 weeks . This interval can be decreased to 5-12 days with the radiometric BACTEC TB system and to 12-19 days with Septi-Chek AFB . For diagnosis of MAC bacteremia, blood is inoculated directly into a BACTEC TB 13A blood culture vial . For quantitative cultures, blood is collected in an Isolator lysis-centrifugation tube, and the sediment of the processed sample is inoculated onto agar plates . MAC is identified by conventional biochemical tests, which take several weeks or months, or with commercial DNA probes or chromatography, each of which provides results in a few hours . No standardized reference method for antimicrobial susceptibility testing exists, and no correlation between in vitro results and clinical efficacy is clear . Isolates appear more sensitive in broth than on agar . Evaluation of susceptibility in macrophage and animal models is helpful because drugs concentrated in cells may be more efficacious against MAC--an intracellular pathogen--than would be predicted by results in cell-free systems.

Biochim Biophys Acta, 1994 Mar 31, 1221(2), 109 - 14
Seminal plasmin, a bovine seminal plasma protein, lyses dividing but not resting mammalian cells; Murti TR et al.; Seminal plasmin, an antimicrobial and transcription-inhibitory protein of bovine seminal plasma, is shown to lyse dividing mammalian cells in vitro . It lyses cells in culture such as CHO, Vero, HeLa and L929 . It also lyses regenerating rat liver parenchymal cells and cells of two ascitic tumours of rat--the Zajdela ascitic hepatoma and the AK-5 . However, it does not lyse resting cells such as adult liver parenchymal cells, erythrocytes, or resting lymphocytes, though it binds to their cell surface . It can be used, therefore, to distinguish cells that are in the division cycle from cells that are in the resting phase . The cell-lytic activity of seminal plasmin is inhibited by Ca2+.

Proc Natl Acad Sci U S A, 1994 Mar 29, 91(7), 2430 - 5
Effect of changes in human ecology and behavior on patterns of sexually transmitted diseases, including human immunodeficiency virus infection; Wasserheit JN; The last 20 years have witnessed six striking changes in patterns of sexually transmitted diseases (STDs): emergence of new STD organisms and etiologies, reemergence of old STDs, shifts in the populations in which STDs are concentrated, shifts in the etiological spectra of STD syndromes, alterations in the incidence of STD complications, and increases in antimicrobial resistance . For example, human immunodeficiency virus (HIV) emerged to devastate the United States with a fatal pandemic involving at least 1 million people . The incidence of syphilis rose progressively after 1956 to reach a 40-year peak by 1990 . In both cases, disease patterns shifted from homosexual men to include minority heterosexuals . Over the last decade, gonorrhea became increasingly concentrated among adolescents, and several new types of antimicrobial resistance appeared . Three interrelated types of environments affect STD patterns . The microbiologic, hormonal, and immunologic microenvironments most directly influence susceptibility, infectiousness, and development of sequelae . These microenvironments are shaped, in part, by the personal environments created by an individual's sexual, substance-use, and health-related behaviors . The personal environments are also important determinants of acquisition of infection and development of sequelae but, in addition, they mediate risk of exposure to infection . These are, therefore, the environments that most directly affect changing disease patterns . Finally, individuals' personal environments are, in turn, molded by powerful macroenvironmental forces, including socioeconomic, demographic, geographic, political, epidemiologic, and technological factors . Over the past 20 years, the profound changes that have occurred in many aspects of the personal environment and the macroenvironment have been reflected in new STD patterns.

Biochemistry, 1994 Mar 22, 33(11), 3342 - 9
Orientational and aggregational states of magainin 2 in phospholipid bilayers; Matsuzaki K et al.; Magainins from Xenopus skin are antimicrobial peptides with broad spectra, and their action mechanisms are considered to be the permeabilization of bacterial membranes . To elucidate their molecular mechanisms, three analog peptides of magainin 2, each having a Trp residue substituted for Phe at the 5th, 12th, or 16th position, were synthesized, and their interactions with acidic phospholipid membranes were investigated by fluorescence . The Trp substitution did not significantly affect the properties of the parent peptide . The binding isotherms of these peptides to the membranes, which were obtained on the basis of fluorescence changes upon membrane binding of the peptides, were sigmoidal, suggesting the association of the bound peptide molecules . A quantitative analysis indicated that the formed aggregate is a dimer . The observation that the initial rate constant of magainin 2 induced leakage of calcein from liposomes was dependent on the fourth power of the peptide concentration demonstrates the formation of a tetrameric pore . A blue shift and intensity enhancement of Trp fluorescence in the presence of the membranes indicate that those Trp residues are buried in the hydrophobic region of the bilayers . Furthermore, the depths of the Trp residues, which were determined using the n-doxylphosphatidylcholine quenching technique, were about 10 A from the bilayer center irrespective of the peptide aggregational state . Thus, it was concluded that the orientation of the magainin 2 alpha-helix is parallel to the membrane surface . A model of the pore formation will be proposed on the basis of these observations.

J Biol Chem, 1994 Mar 18, 269(11), 7855 - 8
Molecular cloning and chemical synthesis of a novel antibacterial peptide derived from pig myeloid cells; Zanetti M et al.; A group of myeloid precursors of defense peptides has recently been shown to have highly homologous N-terminal regions . Using a strategy based on this homology, a novel cDNA was cloned from pig bone marrow RNA and found to encode a 153-residue polypeptide . This comprises a highly conserved region encompassing a 29-residue signal peptide and a 101-residue prosequence, followed by a unique, 23-residue, cationic, C-terminal sequence . A peptide corresponding to this C-terminal sequence was chemically synthesized and shown to exert antimicrobial activity against both Gram positive and negative bacteria at concentrations of 2-16 microM . The activity of this potent and structurally novel antibacterial peptide appears to be mediated by its ability to damage bacterial membranes, as shown by the rapid permeabilization of the inner membrane of Escherichia coli.

Med Klin (Munich), 1994 Mar 15, 89(3), 114 - 23
{Empirical antimicrobial therapy in neutropenic patients . Results of a multicenter study by the Infections in Hematology Study Group of the Paul Ehrlich Society}; Maschmeyer G et al.; BACKGROUND: Severe infections are the predominant cause of treatment failure in patients with high grade malignant hematological disorders undergoing intensive chemotherapy . PATIENTS AND METHODS: In a multicenter trial of the Paul Ehrlich Society (PEG) study group, febrile neutropenic patients with acute leukemias or other high grade hematological malignancies were randomized for a three phase sequential antimicrobial intervention comparing different widely applied regimes for empirical therapy . Patients with clinically documented infections were treated according to a modification depending on the respective source of infection, whereas in patients with microbiologically documented infections, treatment could be adapted to the sesceptibility patterns of detected pathogens . Criteria for evaluation as well as time points for response assessment and treatment escalation were strictly prescribed by the study protocol . RESULTS: Of 1573 evaluable patients, 50.9% had fever of unknown origin (FUO) throughout the study period, 17.1% had lung infiltrates, 14.1% primary bacteremia or fungemia (B/F), 12.6% other clinically documented (CDI) and 5.3% other clinically as well as microbiologically documented infections (CMDI) . Cumulative response rate (CR) in patients with FUO was 91.3%, a significant difference between various regimens could not be detected in either of the three treatment phases . Patients with lung infiltrates had a significantly worse treatment outcome as compared to patients with other documented infections or with FUO (61.3% vs 82.9% vs 91.3%) . Gram-positive pathogens dominated in case of microbiologically documented infections (MDI), whereas the proportion of fungal infections increased dramatically in MDI with pathogens detected only after more than six days under study . Of numerous prognostic factors analyzed, only the trend in white blood cell counts had a significant impact on treatment outcome . CONCLUSION: Infection-related mortality in neutropenic patients with high grade hematological malignancies can be markedly reduced by a systematically escalating interventional antimicrobial therapy . Early systemic antifungal treatment, especially in patients with lung infiltrates, might further improve treatment results.

Med Tekh, 1994 Mar-Apr, (2), 9 - 11
{BOP-polymer implants for fixation of tubular bones and replacement of osseous tissue defects}; Belykh SI; The paper provides the functional characteristics of and clinical findings of the employment of 4 pins for osteosynthesis from biocompatible polymers and shows that the pins ensure reliable fixation of bone fragments and due to their ability to resolve in the body they require no repeated operations for their extraction . The application of the polymer pins substantially widens the scopes for reconstructive operations, enables additional fixation to eliminate rotor mobility, additional fixation of bone fragments, allowing for combined osteosynthesis in fractures of the upper and lower thirds of bones . The employment of antimicrobial pins allows one to prevent postoperative suppurations in open fractures and to treat osteomyelitis . The developed material to fill bone defects with PPV ensures a rapid filling of osseous cavilities with its intrinsic osseous regenerates, recovery of normal osseous tissue in Perthes' disease, and fixation of endoprostheses . The author presents a procedure for applying a kit for replacement of skull defects and indicates that the material substitutes defects of various outlines and rapidly restores the strength characteristics of the skull.

Med Tekh, 1994 Mar-Apr, (2), 32 - 4
{Kapromed - antibacterial suture material}; Volenko AV et al.; The paper gives data on the composition and strength characteristics and experimental and clinical findings of resolving antimicrobial suture materials, such as Capromed-type one, based on the modified caproic fiber coated by the biocompatible polymer PPB-1 which contains antimicrobial drugs . Capromed threads are demonstrated to have high strength characteristics and resolve in the body within 8-9 months . Coating the modified caproic fibers with the biocompatible copolymer imparts them pseudomonfilament characteristics and prevents the penetration of cellular elements to the thickness of threads . The content of antibacterial agents in the polymer coating confers prolonged antibacterial properties on Capromed . Desorption of antimicrobial agents from Capromed is conducive to more favourable healing, prevents the development of ligature fistulas, favours an over 4-fold reduction in the incidence of wound complications, as compared to the controls.

Infect Control Hosp Epidemiol, 1994 Mar, 15(3), 189 - 92
Quality standard for the treatment of bacteremia . The Infectious Diseases Society of America; Gross PA et al.; OBJECTIVE: The objective of this quality standard is to optimize the treatment of bacteremia in hospitalized patients by ensuring that the antibiotic given is appropriate in terms of the blood culture susceptibility of the pathogen . Although this standard may appear to be minimal in scope, it is needed because appropriate antimicrobial treatment is not given in 5% to 17% of cases . To implement the standard, physicians, pharmacists, and microbiologists will need to devise a coordinated strategy . OPTIONS: We considered criteria for appropriate dosing, most cost-effective selection, proper antibiotic levels in serum, least toxicity, narrowest spectrum, specific clinical indications, and optimal duration of treatment . All these criteria were rejected as the basis for the standard because they were too controversial and too difficult to be applied by a nonphysician chart reviewer . In contrast, the selection of an antibiotic to which the pathogen is sensitive is a noncontroversial criterion and easy for a chart reviewer to apply . OUTCOMES: The standard is designed to reduce the incidence of adverse outcomes of septicemia such as renal failure, prolonged hospitalization, and death . EVIDENCE: Several well-designed clinical trials without randomization as well as case-controlled studies have confirmed the benefit of using an antibiotic that is appropriate in light of the susceptibility of the isolate in blood culture . Prospective, randomized, placebo-controlled trials are not available . VALUES: Our premise is that the presence of bacteremia is a risk factor for serious adverse outcomes . We also believe that the administration of antibiotics must always be guided by the susceptibility report for the pathogen(s) obtained from blood cultures . This concern is more critical for pathogens from the blood than for those from most other body sites . We had evidence that susceptibility reports for pathogens from positive blood cultures were not always used properly . We used group discussion to reach a consensus among the members of the Quality Standards Subcommittee . BENEFITS, HARMS, AND COSTS: Through the implementation of this standard, at least 5% of bacteremias could be treated more appropriately . An unknown number of deaths would likely be prevented, and mortality from bacteremia treated inappropriately would probably be reduced . The primary undesirable feature of the standard is an increased workload of pharmacists and microbiologists . RECOMMENDATIONS: Treatment of bacteremia with an antibiotic that is appropriate in terms of the pathogen's blood-culture susceptibility is a minimal standard of care for all patients . VALIDATION: We consulted more than 50 experts in infectious diseases from the fields of medicine, surgery, pediatrics, obstetrics and gynecology, nursing, epidemiology, pharmacology, and government . In addition, the methods for its implementation were reviewed by the American Society of Hospital Pharmacists and were tested by one of the members of the Quality Standards Subcommittee . SPONSORS: The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Diseases Society of America (IDSA) developed the standard . The subcommittee was composed of representatives of the IDSA (Drs . Gross and McGowan), the Society for Hospital Epidemiology of America (Dr . Wenzel), the Surgical Infection Society (Dr . Dellinger), the Pediatric Infectious Diseases Society (Dr . Krause), the Centers for Disease Control and Prevention (Dr . Martone), the Obstetrics and Gynecology Infectious Diseases Society (Dr . Sweet), and the Association of Practitioners of Infection Control (Ms . Barrett) . Funding was provided by the IDSA and the other cooperating organizations . This standard is endorsed by the IDSA.

Infect Control Hosp Epidemiol, 1994 Mar, 15(3), 182 - 8
Quality standard for antimicrobial prophylaxis in surgical procedures . The Infectious Diseases Society of America; Dellinger EP et al.; OBJECTIVE: The objectives of this quality standard are 1) to provide an implementation mechanism that will facilitate the reliable administration of prophylactic antimicrobial agents to patients undergoing operative procedures in which such a practice is judged to be beneficial and 2) to provide a guideline that will help local hospital committees formulate policies and set up mechanisms for their implementation . Although standards in the medical literature spell out recommendations for specific procedures, agents, schedules, and doses, other reports document that these standards frequently are not followed in practice . OPTIONS: We have specified the procedures in which the administration of prophylactic antimicrobial agents has been shown to be beneficial, those in which this practice is widely thought to be beneficial but in which compelling evidence is lacking, and those in which this practice is controversial . We have examined the evidence regarding the optimal timing of drug administration, the optimal dose, and the optimal duration of prophylaxis . OUTCOMES: The intended outcome is more uniform and reliable administration of prophylactic antibiotics in those circumstances where their value has been demonstrated or their use has been judged by the local practicing medical community to be desirable . The result should be a reduction in rates of postoperative wound infection with a limitation on the quantities of antimicrobial agents used in circumstances where they are not likely to help . EVIDENCE: Many prospective, randomized, controlled trials comparing placebo with antibiotic and comparing one antibiotic with another have been conducted . In addition, some trials have compared the efficacy of different doses or methods of administration . Other papers have reported on the apparent efficacy of administration at different times and on actual practice in specific communities . Only a small group of relevant articles found through 1993 are cited herein . When authoritative reviews are available, these--rather than an exhaustive list of original references--are cited . VALUES: We assumed that reducing rates of postoperative infection was valuable but that reducing the total amount of antimicrobial agents employed was also worthwhile . The cost of and morbidity attributable to postoperative wound infections should be weighed against the cost and potential morbidity associated with excessive use of antimicrobial agents . BENEFITS, HARMS, AND COSTS: More reliable administration of antimicrobial agents according to recognized guidelines should prevent some postoperative wound infections while lowering the total quantity of these drugs used . No harms are anticipated . The costs involved are those of the efforts needed on a local basis to design and implement the mechanism that supports uniform and reliable administration of prophylactic antibiotics . RECOMMENDATIONS: All patients for whom prophylactic antimicrobial agents are recommended should receive them . The agents given should be appropriate in light of published guidelines . A short duration of prophylaxis (usually < 24 hours) is recommended . VALIDATION: More than 50 experts in infectious disease and 10 experts in surgical infectious disease and surgical subspecialties reviewed the standard . In addition, the methods for its implementation were reviewed by the American Society of Hospital Pharmacists . SPONSORS: The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Disease Society of America (IDSA) developed the standard . The subcommittee was composed of representatives of the IDSA (Drs . Gross and McGowan), the Society for Hospital Epidemiology of America (Dr . Wenzel), the Surgical Infection Society (Dr . Dellinger), the Pediatric Infectious Disease Society (Dr . Krause), the Centers for Disease Control and Prevention (Dr . Martone), the Obstetrics and Gynecology Infectious Diseases Society (Dr . Sweet), and the Association of Practitioners of Infection Contr

Am J Hosp Pharm, 1994 Mar 1, 51(5), 669 - 71
Program for procurement of drugs for indigent patients; Decane BE et al.; A program for procuring free medications for indigent patients from pharmaceutical manufacturers is described . A medical center that provides $36 million in free care annually to indigent patients sought a way to offset drug costs for these patients while maintaining the same level of care . The pharmaceuticals with the greatest impact on the pharmacy budget were identified; manufacturers of these pharmaceuticals were surveyed to determine if they offered free drugs to qualified patients . The net potential cost avoidance resulting from procuring these free drugs was estimated at $150,000 for the first year . A full-time pharmacist was hired to identify patients likely to qualify for such assistance, help patients apply for assistance, and coordinate the receipt and distribution of the resulting medication supplies . The program served 200 patients the first year (fiscal year 1992) and more than 300 patients the next year . Medications obtained for these patients included i.v . immune globulin, cancer chemotherapy agents, growth factors, antimicrobials, antiemetics, and interferons . The acquisition cost of the medications received was $448,851 in 1992 and $504,211 in 1993 . A pharmacy-based program to procure free medications for indigent patients has helped to defray a medical center's expense of providing care.

Am J Hosp Pharm, 1994 Mar 1, 51(5), 631 - 48; quiz 698-9
Infection control in critically ill patients: effects of selective decontamination of the digestive tract; Rogers CJ et al.; The use of selective decontamination of the digestive tract (SDD) to control infection in the intensive care unit (ICU) is reviewed . There are three basic patterns of infection in the ICU: primary endogenous, secondary endogenous, and exogenous . In exogenous infection, no microbial carriage precedes colonization and infection . In endogenous infection, infection is preceded by oropharyngeal or GI carriage . A primary endogenous infection is caused by an organism carried by the patient on admission to the ICU, whereas a secondary endogenous infection is caused by organisms acquired in the ICU . The traditional approach to infection control in the ICU has included frequent hand washing, limiting the use of agents for prophylaxis of stress-ulcer bleeding, and limiting the use of injectable antimicrobials to the treatment of infection in order to prevent resistance . The recognition that hand washing only partially reduces endogenous infection led to the use of nonabsorbable antimicrobials to abolish oropharyngeal and gastrointestinal carriage of potentially pathogenic microorganisms . In addition, the use of an injectable antimicrobial during the first four days in the ICU to control primary endogenous infection was considered not to lead to resistance as long as it was combined with nonabsorbable antimicrobials . Of 41 fully reported clinical trials of SDD, 33 showed a significant reduction of infectious morbidity among patients who received SDD . Of the 32 trials in which carriage of potential pathogens was a measured endpoint, 31 showed a reduction in carriage . Of the 24 studies in which resistance was an endpoint, 22 showed no increase in resistance associated with SDD . Only 10 of 35 trials that examined death showed a significant decrease in mortality . SDD, used in conjunction with traditional infection-control measures, diminishes microbial carriage and infectious morbidity in the ICU without increasing antimicrobial resistance.

Int J Lepr Other Mycobact Dis, 1994 Mar, 62(1), 43 - 7
Therapeutic efficacy of benzoxazinorifamycin, KRM-1648, in combination with other antimicrobials against Mycobacterium leprae infection induced in nude mice; Saito H et al.; In this study, the in vitro and in vivo anti-Mycobacterium leprae activity of the newly developed benzoxazinorifamycin, KRM-1648, in combination with clofazimine (CFZ) or dapsone (DDS) was evaluated . In vitro anti-M . leprae activities of KRM-1648, CFZ, and DDS along with their combinations were measured by the BACTEC 460 TB System . KRM-1648 (0.01 microgram/ml), CFZ (0.5 microgram/ml), and DDS (2.0 micrograms/ml exhibited a significant anti-M . leprae activity, reducing growth index (GI) values by 78%, 30%, and 35% by day 18, respectively . Combinations of KRM-1648 with either CFZ or DDS, or both caused only a slight increase in the efficacy . BALB/c nude mice infected subcutaneously with 1 x 10(6) of M . leprae Thai-53 strain and test drugs were given to mice by gavage once daily six times per week for up to 50 days, from day 31 to day 80 . Animals were observed for the growth of organisms in the hindfoot pad during the 12 months following infection . KRM-1648 given at the dose of 0.001 mg/mouse exhibited potent antileprosy activity . KRM-1648 exhibited a significant combined effect with either CFZ or DDS, or both against M . leprae infection, except that there was no significant difference in efficacy between KRM-1648 + CFZ and CFZ alone . Furthermore, the efficacy was most increased in the three-drug regimen KRM-1648 + CFZ + DDS.

Eur J Pediatr, 1994 Mar, 153(3), 144 - 50
New perspectives in understanding and management of the respiratory disease in cystic fibrosis; Suter S; In the past 40 years, the mean survival of patients with cystic fibrosis (CF) has increased from less than 1 year to 30 years . The identification of the gene mutated in CF in 1989 has already been followed by the first phase of somatic gene therapy in 1993 . The target organ of somatic gene therapy is the respiratory epithelium, which is progressively damaged by the chronic infection and inflammation characteristic of the disease . Since in the future, more patients may benefit from somatic gene therapy, the understanding of the mechanisms leading to chronic infection and inflammation becomes increasingly important . In the future, current therapeutic measures to protect the respiratory epithelium from damage, such as intravenous antimicrobial treatment, will be improved by the additional delivery of new drugs to the bronchial tree by aerosol . Amiloride and recombinant human DNAse administered by this route have the potential to improve mucociliary clearance . Antibiotics as well as protease inhibitors delivered by aerosol should contribute to prevent damage by infection and inflammation in order to increase the probability of successful somatic gene therapy in this disease.

Clin Lab Med, 1994 Mar, 14(1), 69 - 82
General principles in the laboratory detection of bacteremia and fungemia; Wilson ML et al.; Various factors are important in the laboratory detection of bacteremia and fungemia . These include clinical factors, the type of blood culture system, and laboratory processing of blood culture bottles . Most commercial blood culture products have been designed to take these factors into account and, thus, are relatively similar . There are differences, however, and it should not be assumed that these products have identical performance characteristics . To optimize microbial recovery, clinicians should order and collect the proper number of blood cultures at the earliest possible time and before the administration of antimicrobial agents . Clinical microbiologists should select a blood culture system that optimizes the recovery of common microbial pathogens and should use blood culture systems according to the manufacturers' recommendations.

Clin Lab Med, 1994 Mar, 14(1), 181 - 95
Rapid detection and identification of microorganisms from blood cultures; Chorny JA et al.; In an era characterized by increasing emphasis on minimizing laboratory costs, reliable and cost-effective methods for rapidly identifying bacteria and fungi directly from blood cultures have a great deal of appeal to clinical microbiologists . A variety of methods have been evaluated and found to be useful under certain conditions, although none of the methods has been standardized and questions remain as to whether their use improves patient care or reduces hospital costs . Even if these methods do not improve patient care or reduce hospital costs, their use and expense could be justified if they improve laboratory work flow or decrease laboratory costs or both . Several issues remain unresolved, one of which is whether the use of rapid identification methods with a continuous-monitoring blood culture system might allow for a clinically important decrease in the time required to identify blood culture isolates . Another issue is whether subsequent isolation by culture is necessary for microorganisms with predictable antimicrobial susceptibility patterns . These and other issues need to be studied further before the exact clinical usefulness of rapid methods will be known . At this time, no commercial product has been cleared or approved by the Food and Drug Administration (FDA) for the direct detection or identification of both of pathogenic microorganisms from blood culture bottles (Sharon Hansen, PhD, personal communication, 1993) . Consequently, laboratory directors should exercise caution in the use of commercial or other products for direct blood culture testing, because manufacturers assume no liability for products that are used for purposes other than that for which they have been approved . In addition, such use of commercial products may be in violation of the rules set forth in the Clinical Laboratory Improvement Act of 1988 . Furthermore, as discussed previously, the clinical performance characteristics of many products typically have not been determined, and, therefore, test reference ranges, sensitivity, specificity, and positive and negative predictive values have not been established . Other issues, such as the effect of different blood culture media and additives, also have not been studied adequately, nor are specific controls defined . Therefore, laboratory staff who would like to use commercial products to test blood cultures directly must themselves establish the performance characteristics of the product (keeping in mind the issue of liability) or, preferably, persuade manufacturers to sponsor large-scale controlled clinical trials both to establish performance characteristics and to obtain FDA clearance or approval for such usage of the product.(ABSTRACT TRUNCATED AT 400 WORDS)

Clin Lab Med, 1994 Mar, 14(1), 171 - 9
Antimicrobial susceptibility testing and blood cultures; Mirrett S; Susceptibility testing of microorganisms isolated from blood cultures should follow the guidelines of the NCCLS in the selection of antimicrobial agents and the method for testing . Standardized testing can be performed on isolated colonies from pure subcultures of the blood/broth mixture . Direct susceptibility testing can provide results up to 24 hours sooner, but the techniques for testing have not been standardized . The disk diffusion and agar dilution techniques do not utilize automated testing techniques and seem to provide reliable results . Limited studies of direct susceptibility testing using automated procedures have been published, but the results are not conclusive . The number of discrepancies with direct automated procedures in comparison with standardized techniques is low, and most investigators agree that direct testing is appropriate given the rapidity with which the results are available . New resistance patterns for microorganisms are appearing regularly, and the technology for automated procedures is changing rapidly . New clinical evaluations of direct susceptibility testing with larger numbers of microorganisms that include some of the recently described resistant microorganisms would help to clarify the accuracy and reliability of current procedures . Standardized direct susceptibility testing guidelines should be established so that reliability and accuracy can be improved . There is general consensus that repeat testing by standardized techniques is advisable, although the decision as to whether to repeat the test using a standardized method rests with the individual laboratory director based on his or her expertise and experience with the procedures . Each laboratory director should compare the advantages and limitations of direct antimicrobial susceptibility testing with the methodology currently in use and determine the need for repeat testing by standardized techniques.

Clin Lab Med, 1994 Mar, 14(1), 133 - 47
Manual blood culture systems and the antimicrobial removal device; Doern GV; In the midst of technologic advances within blood culture microbiology, several manual blood culture systems, which have an important role in the detection of bacteremia, mycobacteremia, and fungemia, are often overlooked . These include traditional broth-based systems, agar-broth biphasic blood culture techniques, a commercial broth-based manual system in which growth is detected by a broth displacement method, and lysis-centrifugation . This article reviews the operational features, advantages, and disadvantages of each.

Am J Otolaryngol, 1994 Mar-Apr, 15(2), 103 - 8
Current indications for tympanostomy tubes; Handler SD; Current indications for TT placement are (1) persistent SOM that has not responded to a 6 to 12-week course of medical treatment . This includes full and prophylactic doses of antimicrobials (and corticosteroids, as indicated); (2) recurrent AOM (at least three episodes in 6 months or four episodes in 12 months) that does not respond to, or recurs after, antimicrobial prophylaxis; (3) complications of AOM such as meningitis, facial nerve paralysis, coalescent mastoiditis, or brain abscess; and (4) complications of eustachian tube dysfunction such as tympanic membrane retraction with hearing loss, ossicular erosion, and/or retraction pocket formation . It must be emphasized that TT placement in children does not "cure" the condition that led to the surgical intervention . Rather, the TT maintains aeration of the middle ear until the child grows and his eustachian tube function normalizes . These recommendations for TT placement are to be regarded as guidelines, not as absolute requirements . They must be applied individually to each patient and his/her unique situation . Certain factors may influence timing of TT placement and lead to modification of the guidelines as they apply to each child.

Pediatr Infect Dis J, 1994 Mar, 13(3), 197 - 202
Recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of febrile neutropenia: a double blind placebo-controlled study in children; Riikonen P et al.; In a double blind study of 58 episodes of fever and profound neutropenia, children with cancer received either recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo, combined with identical antimicrobial therapy, i.e . imipenem, on admission . The criteria for discontinuation of therapy were identical . A difference was demonstrated both in the number of hospital days, totaling 252 days in the rhGM-CSF group and 354 in the placebo group, days receiving antibiotics (220 vs . 322), and in the resolution of neutropenia (4.5 days vs . 6.0 days; P < 0.05) . The number of episodes requiring antimicrobial therapy for longer than 10 days was 5 of 28 (12%) in the rhGM-CSF group as opposed to 15 of 30 (50%) in the placebo group (P = 0.01) . rhGM-CSF was well-tolerated . We conclude that rhGM-CSF was efficacious in accelerating myeloid recovery and reducing the length of hospitalization in febrile neutropenia.

J Antibiot (Tokyo), 1994 Mar, 47(3), 357 - 69
Synthesis and antibacterial activity of new 2-substituted penems . II; Nishi T et al.; A series of new penems (4-17), having a bicyclic imidazole moiety as the C-2 substituent, has been synthesized . The antimicrobial activity of these compounds and their susceptibility to renal dehydropeptidase-1 (DHP-1) are elucidated, and their structure-activity relationships are discussed.

Soc Sci Med, 1994 Mar, 38(5), 717 - 24
The use of antimicrobial drugs in Nagpur, India . A window on medical care in a developing country; Dua V et al.; The objective of the study was to determine the patterns of use of antimicrobial drugs in the general population of the large, industrial city of Nagpur, India . Interviews of pharmacists and clients were carried out in a stratified, random sample of 34 pharmacies to determine beliefs and practices in prescribing and self-prescribing of antibiotics by complaint, choice of drug, dose, duration, cost, age and sex of the consumers . The study showed that drugs were dispensed without prescription despite prohibition by the Indian Pharmaceutical Act . Sales of antimicrobial drugs accounted for 17.5% of 511 purchases and 23.3% of expenditures for drugs . Proprietary brands of penicillins, co-trimoxazole and tetracyclines were dispensed most often (64.8%) . The most common indications were upper respiratory, gastrointestinal and nonspecific complaints . The median number of units obtained was 5.0 (95% range 1-20), at a median cost of $0.50 per purchase, usually taken for less than five days . Repeat purchases were made without consulting a physician . Almost two thirds of purchases (63.9%) were for males, mainly under the age of ten years . Clients had poor knowledge of the indications, side effects, adverse reactions and appropriate duration of therapy . The dispenser viewed himself as a businessman rather than a professional and rarely offered unsolicited advice . Co-prescribing of 'tonics' added to costs and decreased the purchasing power for antimicrobial drugs . Most purchases of antimicrobial drugs in community pharmacies in Nagpur were for minor indications and were limited by the purchasing power of the consumers . It is doubtful that the choice of drug and the short duration of therapy would be effective for serious infections.(ABSTRACT TRUNCATED AT 250 WORDS)

J Dent Res, 1994 Mar, 73(3), 695 - 703
Procedures for establishing efficacy of antimicrobial agents for chemotherapeutic caries prevention; ten Cate JM et al.; Chemotherapeutics are presently considered for use in caries-preventive programs . The laboratory and in vivo testing of these agents, to some extent, parallels the methodology developed for the evaluation of fluoride products . However, fluoride is primarily effective by interfering with the de- and remineralization balance between enamel and the oral fluids . Antimicrobial and chemotherapeutic agents interfere with the bacterial colonization, growth, and metabolism of dental plaque . The initial selection of promising agents is done, therefore, by determination of the minimum inhibitory concentration (MIC) against a wide range of relevant bacterial species, together with tests of the effects of sub-MIC levels on the expression of virulence factors . In the hierarchy of tests proposed in this paper, studies of bacterial adhesion and enamel caries models form the next phase in the evaluation of agents . Also, mixed-culture studies are recommended to determine how a treatment perturbs a stable microflora . A final stage before clinical testing might involve intra-oral studies on limited numbers of volunteers . These should be tests of intra-oral substantivity and activity of the agents in formulated products, and in situ models of enamel caries lesion formation and remineralization . The latter type of study seems particularly appropriate to ensure that new agents do not decrease the efficacy of the other active components (e.g., fluoride) in caries-preventive products.

J Infect Dis, 1994 Mar, 169(3), 575 - 80
Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibiotics against Mycobacterium avium complex infection in the beige mouse model; Bermudez LE et al.; Previous studies have shown that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates human and murine macrophages to inhibit growth and kill intracellularly . This study shows the effect of GM-CSF on Mycobacterium avium complex (MAC) infection in vivo using a C57BL/6 beige mouse model of disseminated MAC infection . Furthermore, it examined the activity of the combination of GM-CSF and amikacin or azithromycin, two antimicrobials active against MAC, on the survival of MAC within macrophages in vitro and in the mouse model of disseminated infection . Although GM-CSF (25 mg/kg) induced mycobactericidal and mycobacteriostatic activity in macrophages in vitro and in vivo, the combination of GM-CSF and amikacin (50 mg/kg) or azithromycin (250 mg/kg) was associated with a significant increase in killing of MAC both within cultured macrophages and in the beige mouse model . Therefore, a significant reduction in the number of viable bacteria was observed in blood, liver, and spleen of mice treated with a combination of GM-CSF and azithromycin or amikacin compared with control mice and those treated with GM-CSF or antimicrobials alone.

Hokkaido Igaku Zasshi, 1994 Mar, 69(2), 182 - 7
{Aspects of disinfectants for control of nosocomial infections}; Chiba K; Use of disinfectants is regarded as the most important procedure for preventing the transmission of nosocomial infections . Because microorganisms exhibit a wide range of resistance to disinfectants, it follows that the kinds of microorganisms known and the characteristics of selected disinfectants must be consideration . Chemical disinfectants can be classified to three categories according to its germicidal action, namely, high-, intermediate-and low -level disinfectant . The efficacy of disinfection is affected by a number of factors, each of which nullify or limit the efficacy of the process . Some of the factors are the organic load on the object; the prior cleaning of the object; the type and level of microbial contamination; the concentration of and exposure time to the germicide; the temperature and pH of the disinfection process . Handwashing is the single most important procedure for preventing nosocomial infections . Although plain soaps have been shown to be adequate for routine handwashing in the absence of a true emergency, antimicrobial handwashing products should be used for handwashing before personnel take care of newborns, severely immunocompromised patients and patients in high-risk units . It will be possible to reduce the nosocomial infection that the use of rationale handwashing technique, motivation and knowledge about the importance of handwashing are achieved.

Gut, 1994 Mar, 35(3), 323 - 6
Eradication of Helicobacter pylori with clarithromycin and omeprazole; Logan RP et al.; Clarithromycin, a new and well tolerated, acid stable macrolide antibiotic, has a similar antimicrobial spectrum to erythromycin but a better in vitro MIC90 (0.03 microgram/l-1) against Helicobacter pylori (H pylori) . This study aimed at determining the eradication rate using clarithromycin 500 mg thrice daily and omeprazole 40 mg daily for two weeks . Patients were given an endoscopy and H pylori status assessed by antral culture (microaerobic conditions, for up to 10 days), antral and corpus histology tests (haematoxylin and eosin/Gimenez stains), and 13C-urea breath test (13C-UBT, European standard protocol, positive result = excess delta 13CO2 excretion > 5 per mil) . Compliance was assessed by returned tablet counts . H pylori clearance at the end of treatment and eradication four weeks after finishing treatment were assessed by the 13C-UBT . Seventy three patients (54 men, median age 45 years) with duodenal ulcers (n = 42) or duodenitis/non-ulcer dyspepsia (n = 31) all with a positive 13C-UBT (mean (SEM) excess delta-13CO2 excretion = 26.6 (4.9) per mil) and either positive antral histology (n = 72) or positive antral culture (n = 35) were studied . Before treatment 2/27 (7%) isolates of H pylori were resistant to clarithromycin and five isolates were resistant to metronidazole . In 70/73 (96%) the 13C-UBT was negative immediately after finishing treatment . Four weeks later the 13C-UBT was negative in 57/73 (mean (SEM) excess delta 13CO2 excretion = 1.2 (0.3) per mil, eradication rate = 78%) . Forty eight (66%) patients experienced a metallic taste while taking the tablets . Although four (5%) patients, however, could not complete the course of treatment, in only one of these four was H pylori not eradicated . These results show that duel therapy with clarithromycin and omeprazole is well tolerated . With an eradication rate of 78% it is an effective treatment for metronidazole resistant H pylori and may be an alternative to standard triple therapy.

Clin Exp Immunol, 1994 Mar, 95(3), 485 - 9
Antimicrobial action of antibodies against Giardia muris trophozoites; Belosevic M et al.; The activities of immune serum and trophozoite-specific MoAb were examined in vitro and in vivo . Immune serum and anti-Giardia muris MoAb caused immobilization of the trophozoites in vitro and were cytotoxic for trophozoites in the presence of exogenous complement . Both immune serum obtained from experimentally infected mice and anti-G . muris MoAb administered directly into the duodenum of mice significantly reduced the number of trophozoites in the small intestine during the acute phase of the infection . These results suggest that serum antibodies play a central role in the elimination of the primary Giardia infection.

Chemotherapy, 1994 Mar-Apr, 40(2), 99 - 103
Enhanced susceptibility of Escherichia coli pretreated with RP7293 to leukocyte activity: comparison with other antimicrobial agents; Perez P et al.; Antimicrobial agents may interact with polymorphonuclear leukocytes and directly modify the leukocyte functions, or bacteria can be modified by the antimicrobial agents causing them to be treated differently by phagocytic cells . Brief exposure of bacteria to high levels of antimicrobials can affect their interaction with leukocytes . The susceptibility of Escherichia coli to phagocytosis and killing by human polymorphonuclear leukocytes in the presence of normal human serum following treatment with RP7293, a new natural streptogramin, was examined, and a comparison made with clavulanic acid/amoxicillin, ciprofloxacin and fosfomycin . Pretreatment of E . coli for 10 min with 4 x MIC of RP7293 clearly sensitized the bacteria to leukocytic killing in the presence of normal human serum (10% v/v).

Gan To Kagaku Ryoho, 1994 Mar, 21(4), 409 - 16
{Treatment of cancer and counter-measures for MRSA infections}; Tanaka K et al.; Patients with malignancy, especially those with hematological malignancy, are well known to be very susceptible to infection in general, because of bone marrow suppression induced by anticancer chemotherapy in addition to the nature of the disease itself . Accordingly, the risk of MRSA infection is very high in these patients, and the infection is often fatal . In an attempt to establish effective measures to prevent MRSA infection, we investigated the nosocomial spread of strains of MRSA and studied the characteristics of patients from the clinical standpoint . We found that strict isolation of patients with MRSA infection is an urgent necessity to prevent the intrahospital spread of MRSA strains and that disinfection of the hands of medical staff and sterilization of the environment are extremely important . In addition, due care must be taken to select an adequate antimicrobial agent and to determine the optimal dose and period for treatment of the infection in patients with malignancy to avoid selecting MRSA strains or inducing resistance in mecA positive strains of S . aureus . For treatment of MRSA infections in patients with malignancy, a combination chemotherapy with vancomycin (VCM), or arbekacin (ABK) plus beta-lactam antibiotic is recommended, and granulocyte colony stimulating factor (G-CSF) is clinically useful when the granulocytopenia was induced by chemotherapy.

Geriatrics, 1994 Mar, 49(3), 24 - 6, 31-6
Community-acquired pneumonia: new outpatient guidelines based on age, severity of illness; Whitson B et al.; Pneumonia is a common and important infectious disease in all age groups but especially in the elderly . Mortality and morbidity are quite high when associated with certain risk factors such as comorbid medical conditions and clinical features that implicate more severe disease . In the absence of such features, patients can be treated quite safely out of the hospital, as long as followup and compliance issues are not a problem . Therapy should be directed toward gram-positive and gram-negative aerobic bacteria and, at times, be further expanded to cover atypical organisms such as Legionella sp . Appropriate antimicrobial agents are those that not only cover expected microorganisms but are compatible with each patient's existing medical regimen.

Dev Biol, 1994 Mar, 162(1), 123 - 33
Expression of magainin antimicrobial peptide genes in the developing granular glands of Xenopus skin and induction by thyroid hormone; Reilly DS et al.; The granular gland of amphibian skin is an epithelial derivative that first appears during metamorphosis . The granular glands of Xenopus laevis are an abundant source of magainins, a family of peptides with antimicrobial activity in vitro . We demonstrate the developmental expression and thyroid hormone induction of magainin and PGLa (peptide with aminoterminal glycine and carboxyterminal leucinamide), the two most abundant members of the magainin peptide family . Magainin and PGLa mRNA levels increase dramatically over the 2-day period between stage 58 and stage 60 and remain high during the remainder of metamorphosis . We used in situ hybridization to localize magainin and PGLa mRNAs to the developing granular gland . Magainin and PGLa peptides are also first detected during metamorphosis, as demonstrated by extraction of active peptides from stage 60 tadpoles and immunogold histochemical localization of magainin and PGLa to the granules of the skin granular gland . We demonstrate the premature induction of magainin and PGLa expression upon administration of exogenous thyroid hormone to stage 54 tadpoles . Further investigation of the developmental expression and induction of the magainin peptides will provide insight into their possible biological functions during Xenopus metamorphosis.

Crit Care Med, 1994 Mar, 22(3), 448 - 54
Interleukin-6 and interleukin-8 concentrations as predictors of outcome in ventricular assist device patients before heart transplantation; Hummel M et al.; OBJECTIVE: To determine whether the serum concentrations of some circulating cytokines (as highly sensitive markers of inflammation) are of value in predicting the outcome of patients with cardiogenic shock and end-stage heart disease, who undergo ventricular assist device implantation until heart transplantation . DESIGN: Cohort study . SETTING: University teaching hospitals . PATIENTS: Twenty patients with cardiogenic shock or end-stage heart disease were consecutively selected for this study, if assist device implantation was performed as a bridge to heart transplantation . MEASUREMENTS AND MAIN RESULTS: The circulating concentrations of the cytokines interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha were monitored from the beginning to the end of assist device support two to three times a week, using commercial enzyme-linked immunosorbent assays (ELISA) . In all patients, circulating IL-6 and IL-8 values were increased shortly after assist device implantation . In patients with uncomplicated courses, IL-6 and IL-8 concentrations decreased after an initial increase and were low at the time of transplantation, whereas serum cytokine concentrations increased and remained increased in the nonsurvivors (survivors vs . nonsurvivors, p < .001) . Circulating IL-1 beta and TNF-alpha concentrations were rarely detectable . CONCLUSIONS: Monitoring of IL-6 and IL-8 values during ventricular assist device support provides a means of early identification of high-risk patients that may allow optimization of antimicrobial therapy and selection of the appropriate time for transplantation.

J Pediatr, 1994 Mar, 124(3), 355 - 67
Clinical efficacy of antimicrobial drugs for acute otitis media: metaanalysis of 5400 children from thirty-three randomized trials; Rosenfeld RM et al.; OBJECTIVE: To reconcile conflicting published reports concerning the absolute and comparative clinical efficacy of antimicrobial drugs for acute otitis media in children . STUDY SELECTION: Articles were identified by MEDLINE search, Current Contents, and references from review articles, textbook chapters, and retrieved reports . Randomized, controlled trials of therapeutic antimicrobial drugs used in the initial empiric therapy for simple acute otitis media were selected by independent, blinded observers, and scored on 11 measures of study validity . Thirty English and three foreign-language articles met all inclusion criteria . DATA EXTRACTION: Data were abstracted for an end point of complete clinical resolution (primary control), exclusive of middle ear effusion, within 7 to 14 days after therapy started . DATA SYNTHESIS: The spontaneous rate of primary control--without antibiotics or tympanocentesis--was 81% (95% confidence interval, 69% to 94%) . Compared with placebo or no drug, antimicrobial therapy increased primary control by 13.7% (95% confidence interval, 8.2% to 19.2%) . No significant differences were found in the comparative efficacy of various antimicrobial agents . Extending antimicrobial coverage to include beta-lactamase-producing organisms did not significantly increase the rates of primary control or resolution of middle ear effusion . Pretreatment tympanocentesis was positively associated with individual group primary control rates, negatively associated with the ability to detect differences in clinical efficacy and unassociated with resolution of MEE . CONCLUSIONS: Antimicrobial drugs have a modest but significant impact on the primary control of acute otitis media . Treatment with beta-lactamase-stable agents does not increase resolution of acute symptoms or middle ear effusion; initial therapy should be guided by considerations of safety, tolerability, and affordability, and not by the theoretical advantage of an extended antibacterial spectrum.

Gastroenterology, 1994 Mar, 106(3), 624 - 8
Effects of LY267108, an erythromycin analogue derivative, on lower esophageal sphincter function in the cat; Greenwood B et al.; BACKGROUND/AIMS: Erythromycin (EM-A) and some of its analogues stimulate gastrointestinal smooth muscle contractions . Because gastroesophageal reflux disease (GERD) in humans is in part caused by a reduction in lower esophageal sphincter (LES) pressure, the aim of this study was to investigate the effect of LY267108 (an EM-A analogue with no significant antimicrobial activity) on LES function . METHODS: In ketamine-anesthetized cats, LES pressure was recorded using a Dent sleeve . RESULTS: In cats, LY267108 increased LES pressure, as did motilin and EM-A . Neither LY267108, EM-A, nor motilin altered LES relaxation in response to a swallow . LY267108 increased LES pressure in cats in which the basal LES pressure was lowered experimentally by perfusing the distal esophagus with HCl (0.1 N for 3 days) or following isoproterenol (3.0 micrograms/kg intravenously) . In summary, LY267108 increases LES pressure in normal cats, did not affect the relaxation of the LES in response to a swallow, and increases LES pressure in animals with an experimentally induced decrease in LES pressure . CONCLUSIONS: The results suggest that LY267108 may be useful in treating GERD because of its ability to increase LES pressure and thus present a barrier for gastroesophageal reflux.

Dev Comp Immunol, 1994 Mar-Apr, 18(2), 89 - 96
Hemocyte-derived reactive oxygen intermediate production in four bivalve mollusks; Anderson RS; Luminol-dependent chemiluminescence (LDCL) and nitroblue tetrazolium (NBT) reduction assays have been used to measure reactive oxygen intermediate (ROI) production by oyster (Crassostrea virginica) hemocytes, as well as ROI modulation caused by disease or exposure to environmental toxicants . However, ROI responses measured by these tests apparently vary considerably among other bivalve species . In all species tested, unstimulated hemocytes produced small quantities of ROIs . In C . virginica and Geukensia demissa phagocytosis or treatment with phorbol myristate acetate triggered significantly augmented, but kinetically dissimilar, ROI responses; however, no induction was recorded in two clam species (Mya arenaria and Mercenaria mercenaria) . This was supported by both LDCL and NBT assays, measuring activity of the myeloperoxidase/hydrogen peroxide system and production of intracellular superoxide anion, respectively . The failure of the clams to respond to standard ROI-eliciting procedures is possibly indicative of interspecies differences in hemocyte-mediated antimicrobial defense mechanisms.

Prikl Biokhim Mikrobiol, 1994 Mar-Apr, 30(3), 420 - 4
{Variability of mycelial microorganisms in space flight}; Aitkhozhina NA et al.; The effect of space flight factors on the mycelial procaryotic (Streptomyces roseoflavus var . roseofungini) and eucaryotic (Fusarium bulbigenum var blasticola) microorganisms has been studied . Phenotypical changes were observed in all the strains studied . The ability to form secondary colonies decreased with reduction of the time interval between inoculation and spacecraft launch . The antimicrobial spectrum of Str . roseoflavus, a producer of an antifungal antibiotic, changed too.

Farmaco, 1994 Mar, 49(3), 201 - 4
Synthesis and antibacterial properties of 7 beta-{2-(5-substituted-or unsubstituted-2-furyl)acetamido}cephalosporanic acid derivatives; Veverka M; Several new 7 beta-{2-(5-substituted or unsubstituted-2-furyl) acetamido}cephalosporanic acid derivatives with various hydrophilic groups on the triazole at the C-3 position of the cephem nucleus were synthetised . The antimicrobial activity of the prepared compounds was tested.

Scand J Soc Med, 1994 Mar, 22(1), 35 - 40
Quality assurance of a diarrhoea control programme in northeastern Brazil; Barros FC et al.; In this study quality assurance methods were used in an evaluation of a programme for Control of Diarrhoeal Diseases (CDD) in northeastern Brazil . Seventy-eight randomly selected public primary care facilities in four states were assessed by trained surveyors . Problems observed in the facilities were lack of information on target population and coverage, lack of equipment to permit rehydration in the premises, and frequent unavailability of trained professionals . Health workers showed deficiencies in history taking, physical examination and knowledge on diarrhoea management . Many caretakers had difficulties in recalling information given to them in the health facilities . Eighty-four percent of the cases were treated with oral rehydration, but 90% were sent home immediately and not kept in the facilities to practice rehydration under guidance as recommended by the national CDD programme . An overuse of the medical treatment was observed . More than two-thirds of health professionals gave wrong indications for use of antibiotics . The study showed that oral rehydration therapy is well established in the government health services in the region but that the CDD programme needs to take early action to correct deficiencies in logistics, case management and health educationPIP: The 9 states in the northeast of Brazil were divided into 4 groups based on population size and geographical distribution . In the capital cities of each state, 5-8 health units treating children with diarrhea were chosen at random . Overall, 78 health care units were studied . University-trained nurses evaluated each health care unit regarding diarrhea management and conducted interviews using questionnaires for the data collection . The survey team was split into groups of 4, each group covering 1 state . The field-work was carried out in May 1989 and took 4-6 weeks to complete . 88% of facilities surveyed were health centers, while the rest were outpatient departments in hospitals . In 40% of the facilities, the number of monthly consultations of children was known, while only 22% had information on the number of children attending for diarrhea each month . 62% of facilities had a special oral rehydration therapy (ORT) place for children . Utensils for administration of ORT were available in only half of the facilities . In 1/5 of the facilities the sugar-salt-solution packets were never or seldom available . In 32 of 65 facilities, the most recent shipment of ORS packets had arrived in the last month . 10 facilities had not received ORS for more than 6 months . In 67 facilities (86%) a physician, and in 9 a health auxiliary, was responsible for managing childhood diarrhea . 75 visits for childhood diarrhea were observed in 42 health facilities . 58 of the attendances (77%) were managed by doctors, 12 by health auxiliaries, and 5 by nurses . 90% of the patients were sent home, while the rest were treated . In 84% of cases oral rehydration therapy was prescribed, usually oral rehydration salts (ORS) . Antimicrobial drugs were prescribed in 21% of the cases . Other drugs like metochlopramide, caolin-pectin, aspirin and vitamins were prescribed in 41% of the cases .

Br Vet J, 1994 Mar-Apr, 150(2), 189 - 96
In vitro studies of Dermatophilus congolensis antimicrobial susceptibility by determining minimal inhibitory and bacteriocidal concentrations; Hermoso de Mendoza J et al.; The Minimal Inhibitory Concentration (MIC) and Minimal Bacteriocidal Concentration (MBC) of 19 antimicrobials on 16 isolates of D . congolensis were determined . The potential field efficacy of the agents was evaluated by comparing the results with serum levels of drug unbound to proteins and the in vitro and in vivo findings of other authors . A modified standard microtechnique was used for serial dilution-antimicrobial sensitivity and found to be easy and reproducible . Erythromycin, spiramycin, penicillin G, ampicillin, chloramphenicol, the streptomycin, amoxicillin, the tetracyclines and novobiocin had high serum concentrations in comparison with their MBCs and were shown to have potential use for the treatment of dermatophilosis.

Infect Dis Clin North Am, 1994 Mar, 8(1), 29 - 45
The sleeping giant . Antimicrobial resistance; Casellas JM et al.; Resistance to most of the antimicrobial agents in use today is present in Latin America as of this publication . Their underlying mechanisms are in place and an even more serious situation is foreseen in the years to come . Both nosocomial and common community-acquired infections have changed to require more complex ways of management . Although newer antibiotics take the place of the older ones, wiser and more restrictive usage of the currently available antibiotics is needed . This may be obtained through education and with the amplification of national and supranational networks of surveillance, which could anticipate trends in resistance.

Infect Dis Clin North Am, 1994 Mar, 8(1), 225 - 41
Brucellosis; Trujillo IZ et al.; Brucellosis remains an endemic disease in many regions of the world, with morbidity much more prevalent in developing countries . Infection is most prevalent in areas in which people are exposed to animals that are carriers of the different brucellae species . By obtaining a definite diagnosis of the disease and treating the patient early in the infection and selecting the appropriate antimicrobial for the particular clinical form of the disease, complete remission of the infection occurs in the majority of cases.

Clin Infect Dis, 1994 Mar, 18(3), 450 - 2
Necrotizing pneumonia caused by mixed infection with Actinobacillus actinomycetemcomitans and Actinomyces israelii: case report and review; Morris JF et al.; Actinobacillus actinomycetemcomitans is an important cause of human pulmonary infections, either alone or with Actinomyces species . It may be critical to isolate Actinobacillus in patients with pulmonary infection for selection of an effective antimicrobial regimen . Clindamycin has superseded penicillin as the sole antimicrobial drug for anaerobic bacterial necrotizing pneumonia and abscess . In the case presented herein, therapy with clindamycin failed to halt worsening necrotizing pneumonia or to prevent hematogenous dissemination . After clindamycin-resistant A . actinomycetemcomitans in addition to Actinomyces israelii were isolated, the patient was treated with penicillin, ciprofloxacin, and cefazolin and was ultimately cured.

Clin Infect Dis, 1994 Mar, 18(3), 428 - 30
Quality standard for the treatment of bacteremia . Infectious Diseases Society of America; Gross PA et al.; OBJECTIVE . The objective of this quality standard is to optimize the treatment of bacteremia in hospitalized patients by ensuring that the antibiotic given is appropriate in terms of the blood culture susceptibility of the pathogen . Although this standard may appear to be minimal in scope, it is needed because appropriate antimicrobial treatment is not given in 5%-17% of cases . To implement the standard, physicians, pharmacists, and microbiologists will need to devise a coordinated strategy . OPTIONS . We considered criteria for appropriate dosing, most cost-effective selection, proper antibiotic levels in serum, least toxicity, narrowest spectrum, specific clinical indications, and optimal duration of treatment . All these criteria were rejected as the basis for the standard because they were too controversial and too difficult to be applied by a nonphysician chart reviewer . In contrast, the selection of an antibiotic to which the pathogen is sensitive is a noncontroversial criterion that is easy for a chart reviewer to apply . OUTCOMES . The standard is designed to reduce the incidence of adverse outcomes of septicemia, such as renal failure, prolonged hospitalization, and death . EVIDENCE . Several well-designed clinical trials without randomization as well as case-controlled studies have confirmed the benefit of using an antibiotic that is appropriate in light of the susceptibility of the isolate in blood culture . Prospective, randomized, placebo-controlled trials are not available . VALUES . Our premise is that the presence of bacteremia is a risk factor for serious adverse outcomes . We also believe that the administration of antibiotics must always be guided by the susceptibility report for the pathogen(s) obtained from blood cultures . This concern is more critical for pathogens from the blood than for those from most other body sites . We had evidence that susceptibility reports for pathogens from positive blood cultures were not always used properly . We used group discussion to reach a consensus among the members of the Quality Standards Subcommittee . BENEFITS, HARMS, AND COSTS . Through the implementation of this standard, at least 5% of cases of bacteremia could be treated more appropriately . An unknown number of deaths would likely be prevented, and mortality from bacteremia treated inappropriately would probably be reduced . The primary undesirable feature of the standard is an increased workload for pharmacists and microbiologists . RECOMMENDATIONS . Treatment of bacteremia with an antibiotic that is appropriate in terms of the pathogen's blood-culture susceptibility is a minimal standard of care for all patients . VALIDATION . We consulted more than 50 experts in infectious diseases from the fields of medicine, surgery, pediatrics, obstetrics and gynecology, nursing, epidemiology, pharmacology, and government . In addition, the methods for its implementation were reviewed by the American Society of Hospital Pharmacists and were tested by one of the members of the Quality Standards Subcommittee . SPONSORS . The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Diseases Society of America (IDSA) developed the standard . The subcommittee was composed of representatives of the IDSA (P.A.G . and J.E.M.), the Society for Hospital Epidemiology of America (R.P.W.), the Surgical Infection Society (E.P.D.), the Pediatric Infectious Diseases Society (P.J.K.), the Centers for Disease Control and Prevention (W.J.M.), the Obstetrics and Gynecology Infectious Diseases Society (R.L.S.), and the Association of Practitioners of Infection Control (T.L.B.) . Funding was provided by the IDSA and the other cooperating organizations . The standard is endorsed by the IDSA.

Clin Infect Dis, 1994 Mar, 18(3), 422 - 7
Quality standard for antimicrobial prophylaxis in surgical procedures . Infectious Diseases Society of America; Dellinger EP et al.; OBJECTIVE . The objectives of this quality standard are (1) to provide an implementation mechanism that will facilitate the reliable administration of prophylactic antimicrobial agents to patients undergoing operative procedures in which such a practice is judged to be beneficial and (2) to provide a guideline that will help local hospital committees formulate policies and set up mechanisms for their implementation . Although standards in the medical literature spell out recommendations for specific procedures, agents, schedules, and doses, other reports document that these standards frequently are not followed in practice . OPTIONS . We have specified the procedures in which the administration of prophylactic antimicrobial agents has been shown to be beneficial, those in which this practice is widely thought to be beneficial but in which compelling evidence is lacking, and those in which this practice is controversial . We have examined the evidence regarding the optimal timing of drug administration, the optimal dose, and the optimal duration of prophylaxis . OUTCOMES . The intended outcome is more uniform and reliable administration of prophylactic antibiotics in those circumstances where their value has been demonstrated or their use has been judged by the local practicing medical community to be desirable . The result should be a reduction in rates of postoperative wound infection in conjunction with a limitation on the quantities of antimicrobial agents used in circumstances where they are not likely to help . EVIDENCE . Many prospective, randomized, controlled trials comparing placebo with antibiotic and comparing one antibiotic with another have been conducted . In addition, some trials have compared the efficacy of different doses or methods of administration . Other papers have reported on the apparent efficacy of administration at different times and on actual practice in specific communities . Only a small group of relevant articles found through 1993 are cited herein . When authoritative reviews are available, these--rather than an exhaustive list of original references--are cited . VALUES . We assumed that reducing rates of postoperative infection was valuable but that reducing the total amount of antimicrobial agents employed was also worthwhile . The cost of and morbidity attributable to postoperative wound infections should be weighted against the cost and potential morbidity associated with excessive use of antimicrobial agents . BENEFITS, HARMS, AND COSTS . More reliable administration of antimicrobial agents according to recognized guidelines should prevent some postoperative wound infections while lowering the total quantity of these drugs used . No harms are anticipated . The costs involved are those of the efforts needed on a local basis to design and implement the mechanism that supports uniform and reliable administration of prophylactic antibiotics . RECOMMENDATIONS . All patients for whom prophylactic antimicrobial agents are recommended should receive them . The agents given should be appropriate in light of published guidelines . A short duration of prophylaxis (usually < 24 hours) is recommended . VALIDATION . More than 50 experts in infectious diseases and 10 experts in surgical infectious diseases and surgical subspecialties reviewed the standard . In addition, the methods for its implementation were reviewed by the American Society of Hospital Pharmacists . SPONSORS . The Quality Standards Subcommittee of the Clinical Affairs Committee of the Infectious Diseases Society of America (IDSA) developed the standard . The subcommittee was composed of representatives of the IDSA (P.A.G . and J.E.M.), the Society for Hospital Epidemiology of America (R.P.W.), the Surgical Infection Society (E.P.D.), the Pediatric Infectious Diseases Society (P.J.K.), the Centers for Disease Control and Prevention (W.J.M.), the Obstetrics and Gynecology Infectious Diseases Society (R.L.S.), and the Association of Practitioners of Infection Control (T.

Boll Chim Farm, 1994 Mar, 133(3), 127 - 43
{The pharmacokinetics of antibiotics: parenteral and oral administration, distribution in the organism, elimination}; Segre G et al.; The efficacy of antimicrobial therapy is largely dependent on the pharmacokinetics of the drug . Pharmacokinetics is the study of the kinetics, that is of the movements of drugs in the body fluids and tissue cells . Often, despite the complexity of mammalian organism, relatively simple compartmental systems are capable to describe the kinetics of many drugs and to provide a rationale in interpreting the experimental results . As most bacterial infections are localized in tissues, the pharmacokinetic modelling of antimicrobial agents should mainly be devoted to clarify the relationship between plasma and tissue drug levels, the former being easily accessible to sampling and the latter more closely related to therapeutic efficacy . In this paper an introduction to pharmacokinetic modelling is presented and the pharmacokinetics of many antimicrobial drugs is discussed.

J Gastroenterol Hepatol, 1994 Mar-Apr, 9(2), 194 - 7
Two cases of Caroli's disease: diagnosis and management; Burt MJ et al.; Caroli's disease is an uncommon congenital malformation involving the intrahepatic bile ducts . This paper reports two cases presenting with biliary tract infection . Diagnosis was established by non-invasive imaging and cholangiography . The infecting organisms were cultured from bile obtained by percutaneous aspiration and the results were used to direct antimicrobial therapy . The role of antibiotics and other management options in preventing recurrent infection is discussed.

Stem Cells, 1994 Mar, 12(2), 154 - 68
Interleukin 12: a key modulator of immune function; Wolf SF et al.; Interleukin (IL)-12 was cloned on the basis of its ability to activate natural killer (NK) cells and promote the development of cytolytic T cells . With further understanding of its activities, IL-12 has emerged as an important cytokine, affecting both immune and hematologic functions . It has been shown to be necessary for the T cell independent induction of interferon (IFN)-gamma, critical for the initial suppression of bacterial and parasitic infection; for the development of a Th1 response, critical for effective host defense against intracellular pathogens; and for the activation of differentiated T lymphocytes of both CD4+ and CD8+ phenotype . IL-12 thus functions to activate and to link the innate and acquired immune responses . The therapeutic potential of these activities is suggested by studies in tumor and microbial models . IL-12 has suppressed tumor growth in all murine models examined . Antimicrobial activity has been demonstrated in bacterial, yeast, parasitic, and viral models of infection . In many of these models, activity has been linked to production of IFN-gamma and, in the parasite model, to development of a Th1 response . In addition to the therapeutic potential associated with IL-12 activity in these disease models, the understanding of its role in immune development and interaction with other cytokines, particularly antagonists, such as IL-4 and IL-10, has clarified and extended our understanding of immune regulation and should lead to significant developments in understanding the progression of AIDS and the development of vaccine adjuvants able to direct the immune response.

Cesk Epidemiol Mikrobiol Imunol, 1994 Mar, 43(1), 21 - 2
{Actinomyces viscosus in subdural empyema}; Bebrova E et al.; The authors describe the finding of Actinomyces viscosus in pus from a subdural empyema in a child patient . When searching for the probable primary source of this uncommon infection of the central nervous system the authors identified by cultivation the same bacterial strain in a periapical dental granuloma . Bacterial diagnosis and radical surgical and antimicrobial therapy led to normalization of a clinical condition with an initially unfavourable prognosis.

J Surg Res, 1994 Mar, 56(3), 256 - 60
Beneficial effects of taurolidine in experimental pancreatitis; Redmond HP et al.; Taurolidine has potent antiendotoxin and antimicrobial effects in vitro . This study assessed the effect of taurolidine in a well-described model of acute pancreatitis . Ninety-five male Wistar rats (250 g) were studied . Pancreatitis was induced by intraductal injection of 50 microliters of a 4% sodium taurocholate solution at a pressure of 25 cm water . Animals were randomly allocated to 1 of 10 groups: 4 groups were used to characterize the model and there were 6 treatment groups . Taurolidine (100 mg/kg) or saline was administered intravenously at Time 1, 4 hr, or 4 and 24 hr following induction of pancreatitis . Serum amylase, endotoxin levels, and blood cultures were assessed at 4 and 24 hr . Survival was documented at 1 week . Serum amylase levels were elevated in animals in whom acute pancreatitis was induced; however, there was no difference in serum amylase between animals treated with taurolidine and those treated with saline . Positive blood cultures were more numerous in saline-treated groups . Treatment with taurolidine was associated with significantly (P < 0.01) lower endotoxin levels (14 +/- 8 pg/ml) compared with saline-treated animals (350 +/- 87 pg/ml) . Taurolidine administration significantly improved survival compared with controls, when given at 4, 24, and 4/24 hr postinduction of pancreatitis (P < 0.05) . Taurolidine was beneficial in this model of acute pancreatitis.

Am J Clin Pathol, 1994 Mar, 101(3), 329 - 37
Application of new technology to the detection, identification, and antimicrobial susceptibility testing of mycobacteria; Pfaller MA; Mycobacteria are reemerging as important causes of human disease . The increase in mycobacterial infections has prompted the development of more rapid and efficient ways of detecting and characterizing mycobacteria in the clinical microbiology laboratory . Methods currently in use or under development include more sensitive methods of direct detection, improved techniques for culture, identification, and susceptibility testing, and the use of nucleic acid probes for identification and epidemiologic typing . Broad application of rapid and sensitive methods for detection and characterization of mycobacteria are essential if we are to limit the spread of Mycobacterium tuberculosis (TB) and provide optimal care for patients infected with TB or other Mycobacterium species.

Mutat Res, 1994 Mar 1, 305(2), 157 - 63
Metabolic activation of four drugs in the eye mosaic assay measuring principally mitotic recombination in Drosophila melanogaster: differences in strain susceptibility and route of exposure; Rodriguez-Arnaiz R et al.; One mycotoxin and three therapeutic drugs widely used in developing countries were examined for genotoxic activity by means of the w/w + somatic recombination assay . Streptozotocin (SZ), an antibiotic antineoplastic agent, gave a frequency of light spots almost one order of magnitude higher than those obtained with the carcinogen mycotoxin sterigmatocystin (STC), the antiprotozoal and antimicrobial metronidazole (MNZ), and the antifungal griseofulvin (GF) . Thus the order of response was SZ > STC > MNZ > GF . Chronic treatment turned out to be the better route of exposure for these genotoxins when compared with surface treatment . The performance of the insecticide-resistant strain Hikone-R was better than that of the wild genotype LS (Leiden Standard) . The positive test results obtained with all four chemicals showed that the P450 system of Drosophila is capable of metabolizing these genotoxins into electrophilic intermediates.

Clin Diagn Lab Immunol, 1994 Mar, 1(2), 145 - 9
Differentiation of borreliacidal activity caused by immune serum or antimicrobial agents by flow cytometry; Liu YF et al.; We demonstrated that borreliacidal activity caused by immune serum and complement can easily be differentiated by flow cytometry from killing activity caused by antimicrobial agents that are commonly used for the treatment of Lyme disease . Assay suspensions containing normal or immune serum were incubated with Borrelia burgdorferi in the presence or absence of ceftriaxone, doxycycline, penicillin, and phosphomycin for 2, 8, 16, and 24 h . Samples containing killing activity were identified by using flow cytometry and acridine orange . In 30 min, the effects of immune serum and complement were easily distinguished from the killing of spirochetes by antimicrobial agents by adding fluorescein isothiocyanate-conjugated goat anti-hamster immunoglobulin . This simple procedure greatly enhanced the usefulness of the borreliacidal assay by eliminating a major source of false-positive reactions.

Toxicology, 1994 Feb 28, 87(1-3), 175 - 88
Anion pores from magainins and related defensive peptides; Duclohier H; The conformations and properties of magainins, powerful antimicrobial peptides isolated from Xenopus laevis skin, are reviewed . Although some emphasis will be placed upon membrane interactions both in living cells and liposomes, we will especially focus on pore-forming properties as studied with conductance measurements on doped planar lipid bilayers . The relevance to channel modelling and engineering will be stressed and finally the relations, analogies and differences, of magainins with other insect and mammalian defensive peptides, such as cecropins and defensins, will be presented.

J Biol Chem, 1994 Feb 18, 269(7), 4928 - 33
Design and synthesis of amphipathic 3(10)-helical peptides and their interactions with phospholipid bilayers and ion channel formation; Iwata T et al.; It has been reported that a peptide corresponding to the S4 segment in sodium channel protein is able to form voltage-dependent cation-selective ion channels (Tosteson, M . T., Auld, D . S., and Tosteson, D . C . (1989) Proc . Natl . Acad . Sci . U . S . A . 86, 707-710) . However, biological and other physical properties remain unexamined . In the present study, three peptides, H-(Ala-Arg-Leu)8-OH (ARL8), H-(Val-Arg-Leu)8-OH (VRL8), and H-(Leu-Arg-Leu)8-OH (LRL8) which were designed on the basis of the S4 segment and expected to form 3(10)-helix, were synthesized and examined with regard to conformational change by the interaction with membranes, membrane perturbation ability, ion channel formation, and antimicrobial activity . According to CD spectra, these peptides were found to form a 3(10)-helical structure in the presence of dipalmitoyl-DL-alpha-phosphatidylcholine/dipalmitoyl-DL-alpha- phosphatidylglycerol (3:1) liposomes . The experiment of the peptide-induced leakage of carboxyfluorescein from liposomes showed that all the peptides had a strong ability to perturb membranes . The peptides were able to form cation-selective ion channels in planar asolectin lipid bilayers . The conductances of the ion channels were small (approximately 2 picosiemens for VRL8 and LRL8 and approximately 23 picosiemens for ARL8), suggesting that the peptides produce narrow pores or wider pores with certain permeable barriers that are a portion of the whole channels . The differences in their conductances depend possibly on the sizes of the side chains of Ala, Val, and Leu residues . However, non of the peptides showed antimicrobial activity (minimum inhibitory concentrations, > 50 micrograms/ml) . Here, we present the first evidence that the peptides can form 3(10)-helical structures with long chain lengths in a lipid bilayer environment.

Anal Biochem, 1994 Feb 15, 217(1), 84 - 90
Purification of antimicrobial peptides from an extract of the skin of Xenopus laevis using heparin-affinity HPLC: characterization by ion-spray mass spectrometry; James S et al.; A simple scheme was developed for the rapid purification of antimicrobial peptides from the skin of Xenopus laevis . An extract of the frog skin was prepared using an acidic medium designed to maximize the solubilization of low-molecular-weight peptides . This extract was subjected to an enrichment procedure using C18 Sep Pak cartridges to yield a salt-free fraction, devoid of high-molecular-weight proteins . This fraction was in turn subjected to heparin affinity high-performance liquid chromatography on a Shodex AF-Pak column . All the antibacterial activity bound to the column and could be eluted using a linear gradient of increasing sodium chloride concentration . Antibacterial activity emerged from the column in fractions corresponding to a sodium chloride concentration of 0.45 M . Reversed-phase high-performance liquid chromatography resolved this material into a series of compounds which could be readily characterized using a combination of amino acid analysis and ion-spray mass spectrometry . Each peptide was found to be antimicrobial and each was positively identified as belonging to a family of amphipathic helix-forming peptides characterized by other investigators . Listed in their order of elution from the reversed-phase column the peptides were magainin 2, magainin 1, peptide-glycine-leucine amide, xenopsin precursor fragment, levitide precursor fragment, and a mixture of fragments derived from the caerulein precursor . These peptides owe their antimicrobial properties to a predeliction to forming amphipathic alpha-helical structures when associated with lipid membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

FEBS Lett, 1994 Feb 14, 339(1-2), 108 - 12
Identification and characterization of a primary antibacterial domain in CAP18, a lipopolysaccharide binding protein from rabbit leukocytes; Tossi A et al.; Secondary structure prediction studies on CAP18, a lipopolysaccharide binding protein from rabbit granulocytes, identified a highly cationic, 21-residue sequence with the tendency to adopt an amphipathic alpha-helical conformation, as observed in many antimicrobial peptides . The corresponding peptide was chemically synthesized and shown to exert a potent bactericidal activity against both Gram-negative and Gram-positive bacteria, and a rapid permeabilization of the inner membrane of Escherichia coli . Five analogues were synthesized to elucidate structure/activity relationships . It was found that helix disruption virtually eliminates antibacterial activity, while the degree of amphipathicity and the presence of an aromatic residue greatly affect the kinetics of bacterial inner membrane permeabilization.

NIH Consens Statement, 1994 Feb 7-9, 12(1), 1 - 23
Helicobacter pylori in peptic ulcer disease; Antimicrobial treatment and prevention of meningitis; Boston University School of Medicine, MAThe efficacy of the conjugate polysaccharide H influenzae type b vaccine has resulted in a reduction in the number of cases of meningitis . Physicians will manage fewer cases of meningitis but they must maintain skills in diagnosis and treatment of the cases that do occur . In addition, to a continuing experience with meningitis due to S pneumoniae and N meningitidis, physicians must be aggressive in obtaining materials for specific diagnosis of aseptic meningitis since many of the infections are treatable with antimicrobial agents . Appropriate treatment of meningitis in children requires knowledge of agents for initial therapy, dosage schedules, changes in the regimen that may be required once the organism is isolated and results of susceptibility tests are available, knowledge of the drugs that require monitoring of serum concentrations to determine safety and efficacy, and antimicrobial prophylaxis for contacts.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 243 - 7
Cytofluorometric analysis of chondrotoxicity of fluoroquinolone antimicrobial agents; Hayem G et al.; To better understand quinolone-related arthropathy, we conceived an experimental ex vivo model using cell cultures of articular chondrocytes issued from pretreated New Zealand White rabbits (NZW) . Juvenile (4- to 5-week-old) NZW were orally dosed with ofloxacin or pefloxacin (300 mg/kg of body weight for 1 day) or with pefloxacin (300 mg/kg for 7 days) . Adult (5-month-old) NZW were treated with pefloxacin (300 mg/kg for 1 day) . Chondrocytes were enzymatically recovered from cartilage and were analyzed by cytofluorometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR), reflecting cellular respiratory-burst activity, and rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), specific for the mitochondrial activity and mass, respectively . A significant increase in the respiratory burst was detected by DCFH-DA and DHR in all treated groups of young animals, compared with untreated control groups . No significant increase of respiratory burst was noted in older treated rabbits . The 7-day treatment resulted in a decrease in mitochondrial uptake of Rh123 and an increase in NAO uptake . Fluoroquinolone arthrotoxicity seems to involve in its early phase the respiratory burst of immature articular chondrocytes.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 200 - 4
In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species; Edelstein PH et al.; The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages . The broth microdilution MICs that inhibited 90% of strains tested were 2 and 1 microgram/ml for ceftriaxone and tazobactam, respectively . Broth macrodilution MICs were 8 and 1 microgram/ml, respectively, for the two Legionella pneumophila strains tested with piperacillin and were 0.25 and 0.5 microgram/ml, respectively, for clavulanate . No significant intracellular anti-L . pneumophila activity was observed for ceftriaxone (32 micrograms/ml), piperacillin (32 micrograms/ml), tazobactam alone (16 micrograms/ml), clavulanate alone (2 micrograms/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 micrograms/ml) or piperacillin (32/4 micrograms/ml) . Erythromycin (1 microgram/ml) was active against intracellular L . pneumophila in the same macrophage model of infection . It is very unlikely that tazobactam or clavulanate, alone or in combination with beta-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans.

Antimicrob Agents Chemother, 1994 Feb, 38(2), 184 - 8
Use of multivariate analysis to compare antimicrobial agents on the basis of in vitro activity data; Hernandez JM et al.; Multivariate techniques such as principal component analysis or similar factor analysis help in analyses of the simultaneous interrelationships among several variables . A comparative multivariate analysis on the in vitro activities of eight antimicrobial agents, including the novel molecule daptomycin, is presented . Multivariate analysis detects components or factors and establishes connections among antimicrobial agents on the basis of their different levels of participation in each factor . The first principal component was dominated by vancomycin, teicoplanin, and rifampin (0.94344, 0.92792, and 0.72127, respectively) . The second principal component showed strong effects from imipenem, gentamicin, and cephalothin (0.87922, 0.86126, and 0.68870, respectively) . Daptomycin stood out alone in the third principal component (0.83983) . The first three components defined 81.5% of the total variance and could easily be represented graphically in a three-dimensional scatter plot . In this graphic representation, the eight antimicrobial agents clustered in three different spatial regions; daptomycin occupied a separate spatial position . The use of multivariate analysis offers a different approach to determination of the in vitro activities of new antimicrobial agents and adds some new data on the relationships among different classes . Notwithstanding its limitations, the application of these methods in microbiology and drug development could be an additional tool for use in processing information.

Prep Biochem, 1994 Feb, 24(1), 15 - 24
A simple and efficient method for the purification of seminal plasmin, an antimicrobial protein from bovine seminal plasma; Kameswari DB et al.; A method involving direct affinity chromatography of undialysed bovine seminal plasma on a calmodulin-agarose column was developed for the purification of seminalplasmin . Seminalplasmin thus obtained was further purified from any contaminants left by ion-exchange chromatography on a short CM-Sepharose column . The method gave an excellent yield of seminalplasmin (0.7 mg per ml seminal plasma) that showed 100% inhibition of bacterial growth at a concentration of 10 micrograms/ml . The purified seminalplasmin was found to be homogeneous as tested by HPLC on a reverse-phase column and SDS-PAGE.

Pediatr Infect Dis J, 1994 Feb, 13(2), 87 - 9
Antimicrobial drug suspensions: a blinded comparison of taste of twelve common pediatric drugs including cefixime, cefpodoxime, cefprozil and loracarbef; Demers DM et al.; We conducted a blinded taste test evaluating 12 antimicrobial suspensions by smell, texture, taste, aftertaste and overall acceptance . Drugs received cumulative scores in each category as well as a total score ranking . Overall Lorabid scored highest but not significantly higher than Keflex, Suprax and Ceclor, all of which score higher than the other test drugs . Cefzil and Augmentin scored just below this group of drugs and higher than all other test drugs . Vantin was inferior to these drugs primarily because of its low score in aftertaste . It was ranked along with V-Cillin-K, Veetids, Sulfatrim and Pediazole, the lowest scoring group of drugs other than Dynapen which scored lower than all other test drugs . No difference overall was detected between the two penicillin VK suspensions evaluated, V-Cillin-K and Veetids.

Pediatr Infect Dis J, 1994 Feb, 13(2), 128 - 33
Clinical significance of fungi isolated from cerebrospinal fluid in children; Arisoy ES et al.; We reviewed the isolation of fungi from cerebrospinal fluid (CSF) cultures at Texas Children's Hospital during the past 6 years to evaluate the significance of a positive culture and to identify potential risk factors . Thirty-seven fungal isolates were recovered from 23 patients representing 2% of all 1498 positive CSF cultures for the study period . Candida species accounted for 94.5% of all fungal isolates . Nine of the 23 patients were newborns and 8 of these were very low birth weight premature neonates . C . albicans was recovered from the CSF of all newborns . Eleven patients were children 4 months to 14 years old . Three patients had positive cultures of CSF obtained on postmortem examination . Leading potential risk factors for positive CSF cultures from neonates included antimicrobial therapy, prematurity, very low birth weight, umbilical catheterization, total parenteral nutrition, intubation and respiratory distress syndrome . For children beyond the newborn period, potential risk factors were antimicrobial therapy for concurrent bacterial infection, chronic systemic or central nervous system disease and central venous cathterization . Disseminated fungal infection was documented in 40% of all patients with positive CSF cultures . Fungi recovered from 7 (35%) of 20 live patients were considered contaminants . We conclude that true fungal meningitis in children is accompanied by multiple positive cultures from CSF or CSF and a second site . A single positive CSF culture for fungi should be considered significant when both CSF findings compatible with meningitis and associated risk factors are present . The isolation of fungi from a single CSF culture can be considered insignificant when CSF findings are within normal limits despite the presence of potential risk factors or vice versa.(ABSTRACT TRUNCATED AT 250 WORDS)

Genomics, 1994 Feb, 19(3), 448 - 53
Structure and diversity of the murine cryptdin gene family; Huttner KM et al.; Cryptdins are antimicrobial peptides of the defensin family produced by mouse intestinal Paneth cells . Characterization of genomic and cDNA clones of cryptdins 1-3, 5, and 6 revealed that each of these genes has a two-exon structure . The prepro- and mature peptide coding regions are found on different exons separated by an intron of approximately 550 bp . The 5' ends of cryptdin mRNAs are distinguished by a 45-nucleotide untranslated sequence (UTS) encoded completely by the first exon . This feature contrasts with the extended 5' UTS of myeloid defensin mRNAs, which are coded by a third exon that appears to be unique to defensin genes expressed in hematopoietic cells . Sequencing of cryptdin cDNAs from both C3H/HeJ and 129/SVJ mouse small intestine demonstrated the presence of at least 16 different mRNAs, identifying cryptdins as the largest known defensin family . Amplification of these two-exon crypt defensin genes, followed by mutation-induced divergence at a limited number of positions, may have played an important role in the development of a broad-spectrum enteric defense system in the mouse.

J Dairy Sci, 1994 Feb, 77(2), 453 - 61
Efficacy of two therapy regimens for treatment of experimentally induced Escherichia coli mastitis in cows; Pyorala S et al.; The objective of the study was to monitor the effect of two therapy regimens on experimental Escherichia coli mastitis . Single udder quarters of 12 cows that were at least 30 d postpartum were inoculated with 1500 cfu of E . coli . The inoculation was repeated in the contralateral quarter after a 3- to 4-wk interval . Initially, half of the cows were treated with antimicrobials, and the remaining half were left untreated . At the second inoculation, the cows that were originally treated were not treated, and vice versa . Therapy began 12 h after inoculation and consisted of parenteral trimethoprim-sulfadiazine (6 cows) or intramammary colistin sulfate (6 cows) . Clinical signs, daily milk yield, bacterial count, and endotoxin content of the milk were recorded . Milk SCC, NAGase activity, and trypsin inhibitor capacity were also monitored . The response to bacterial challenge varied greatly among cows . Bacteria were eliminated from the quarters within 7 d in all but 1 cow . Treatment did not significantly affect the elimination rate of bacteria or any of the measured parameters . Significant positive correlations existed among milk bacterial counts, endotoxin concentrations, and clinical signs at the acute stage of the infection . Based on these findings, antimicrobial therapy of E . coli mastitis during lactation apparently is no more beneficial than no treatment.

Harefuah, 1994 Feb 1, 126(3), 126 - 8, 176, 175
{Antimicrobial sensitivity and treatment of Helicobacter pylori infections}; Moshkowitz M et al.; Helicobacter pylori (HP) is considered the etiological agent of chronic active gastritis and suspicion is strong that it plays an important role in duodenal ulcer . Recently, several clinical studies reported that eradication of HP markedly reduces the frequency of ulcer relapse . Triple-drug treatment, including a bismuth salt and 2 antibiotics (usually metronidazole with either amoxycillin or tetracycline) is considered the treatment of choice . It has been shown that the most important factor for predicting success of treatment is the sensitivity of HP to metronidazole, which varies considerably . In the present study we evaluated antimicrobial susceptibility of 18 HP clinical isolates, as well as effectiveness of triple therapy for eradicating HP infections in 65 patients . In vitro, HP was highly sensitive to amoxycillin, erythromycin and tetracycline (100%), and also to metronidazole and tinidazole (94%) . Sensitivity to chloramphenicol was low (50%) . In our clinical study, the overall eradication rate was 66%; it was higher among women (80%) than men (54%), probably due to better compliance . It is concluded that HP strains in Israel are highly sensitive to metronidazole and that triple therapy is effective, providing compliance is good.

Aust Vet J, 1994 Feb, 71(2), 53 - 7
Adverse drug reactions: report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1993; Maddison JE; Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from April 1992-March 1993 inclusive . The number of reports received/number of animals involved per species was: dogs (30/43); cats (11/14); horses (8/10); cattle (9/30); ferret (1/1) . Of these, 37 (63%) were classified as definite ADRs and 12 (20%) as probable ADRs . In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision . Twenty-three reports involved apparent hypersensitivity reactions and 5 reports were associated with 'off-label' use . Of the definite and probable reports of suspect ADRs the most frequent types of drugs involved were antimicrobials (9 reports), anthelmintics (9 reports), vaccines (7 reports), insecticides (6 reports), vitamin preparations (6 reports), topical anti-inflammatory/antimicrobial/antifungal skin preparations (3 reports) and nonsteroidal anti-inflammatory preparations (3 reports) . Single reports concerning definite or probable ADRs to an anticholinergic, an anaesthetic agent, a corticosteroid, an anabolic steroid and a chondroprotective drug were received.

Q J Med, 1994 Feb, 87(2), 103 - 7
Involvement of the kidneys in Mediterranean spotted fever and murine typhus; Shaked Y et al.; We reviewed 58 patients, 27 with murine typhus (MT) and 31 with Israeli Mediterranean spotted fever (IMSF), hospitalized at the Sheba Medical Center 1979-1988 . Five patients with MT and five with IMSF had evidence of renal impairment . One patient with MT underwent a renal biopsy, and two patients with IMSF died and had autopsy examinations with histology of the kidney . The principal histopathological lesion found in those most severe cases of rickettsiosis-induced renal failure was multifocal perivascular interstitial nephritis . In contrast with previous reports, involvement of the kidneys in rickettsial infection seems to be relatively common . Early diagnosis and treatment with hydration and specific antimicrobial agents is mandatory to prevent morbidity.

Clin Infect Dis, 1994 Feb, 18 Suppl 2, S170 - 9
Molecular events in the activation of human neutrophils for microbial killing; Cohen MS; Human neutrophils provide protection from a variety of microbes; neutropenia or neutrophil dysfunction can both have serious clinical consequences . Effective microbial killing involves attachment to blood vessel walls, transmigration into tissues, chemotaxis, and phagocytosis . The molecular mechanisms by which neutrophils kill microbes have been extensively dissected . Each of the cellular processes is initiated in response to the occupancy of unique surface receptors . Receptor occupancy is translated into specific cellular activities via such signals as activation of calcium-mediated protein kinases and phosphorylation of critical proteins . After phagocytosis, the engulfed particle is subjected to killing mechanisms, which include reactive oxygen species, acid pH, and antimicrobial proteins . A thorough understanding of these molecular events may allow the modulation of neutrophil activity.

Clin Transplant, 1994 Feb, 8(1), 59 - 66
Monitoring of the cellular immune system in patients with biventricular assist devices awaiting cardiac transplantation; Hummel M et al.; Lack of objective parameters to predict the clinical course and outcome are a major problem in managing the patients selected for BVAD-support as a bridge to heart transplantation . This study was intended to assess whether cellular immune parameters have a predictive value for the clinical result of VAD-support . Various cellular immune markers were monitored by multiparameter cytofluorometry in 30 patients who received a VAD system (Berlin Heart) . We did not find significant differences in preoperative values of immune parameters between groups of survivors (n = 14) and non-survivors (n = 16) . All 9 patients who died of septic multiple organ failure (MOF) had shown increased levels of T-cell activation (CD 71, CD 25, HLA-DR) as well as leukocytosis and 7 patients who died of noninfectious complications (mostly hemorrhage or cerebral complications) had exhibited T-lymphopenia . Seven of 9 patients who died of septic MOF had extremely decreased levels of HLA-DR+ monocytes (< 30%) while all 14 survivors and all 7 patients who died of noninfectious complications showed almost normal monocytic HLA-DR antigen expression, antigen-presenting capacity and cytokine secretion . These observations point to the reduced antimicrobial immunity ("immunoparalysis") in the non-survivors and may explain the fatal course of infection in these individuals . The in vitro results of restitution experiments call for new therapeutic strategies to improve the survival of VAD-patients.

Arch Pharm (Weinheim), 1994 Feb, 327(2), 115 - 7
{Actions of new iminium compounds against bacteria and fungi . 30 . 3-alkoxymethyl-1-hexyl-, 3-alkylthiomethyl-1-hexyl-, 3-alkoxymethyl-1-octyl- and 3-alkylthiomethyl-1-octylbenzimidazolium chlorides}; Pernak J et al.; Syntheses and antimicrobial activity of the title compounds are described . They were obtained by reaction of 1-hexyl- or 1-octylbenzimidazol with chloromethylalkyl ether or chloromethylalkyl sulfide . The antibacterial properties were tested on 13 strains of bacteria and fungi . The best antibacterial activity was exhibited by chlorides with octylthiomethyl and decyloxymethyl groups.

Kekkaku, 1994 Feb, 69(2), 113 - 8
{A drug delivery system and biological response modifiers for the treatment of mycobacterial infection}; Koga H et al.; A drug delivery system (DDS) for the treatment of infectious disease has recently been developed . Since liposomal antimicrobial agents are effective on cytozoic bacteria, we applied liposomal streptomycin and amikacin for the treatment of systemic mycobacterial tuberculosis in mice . Liposomal aminoglycosides showed excellent efficacy compared to free aminoglycosides or empty liposome . This therapeutic strategy should be developed for clinical application . Although the human defense mechanism against microbial infection is very complicated, biological response modifiers (BRM) such as vaccination or cytokine therapy have been investigated . One of the most useful and protective vaccines for prevention of tuberculosis is the Mycobacterium vaccae vaccine, developed by Stanford et al . As for the cytokines, interleukin-2, granulocyte macrophage-colony stimulating factor, and tumor necrosis factor have very strong antimycobacterial activity . Interferon alone, however, has weak efficacy, and should be combined with other effective cytokines . These BRM constitute an excellent strategy for antimycobacterial chemotherapy.

Nippon Rinsho, 1994 Feb, 52(2), 339 - 43
{Factors on antimicrobials}; Totsuka K; Infections which are difficult to cure are mainly caused by resistant organisms or opportunistic pathogens . For the treatment of such infections, we should maximize drug's therapeutic potentials, and minimize its toxicity . Characteristics of pharmacodynamics and pharmacokinetics in antimicrobials should be taken into account to maximize the efficacy and to minimize the toxicity . Bactericidal activity and post-antibiotic effect of antimicrobials are the major factors to determine the optimal dosing . Infections caused by intra-phagocytic pathogens should be treated with drugs which penetrate cell well . Early treatment with antimicrobials is the corner-stone for the treatment of infections in immunocompromised host . It is very important to determine which of the two drugs should be given first to maximize the efficacy on combination therapy.

Nippon Rinsho, 1994 Feb, 52(2), 327 - 31
{Mechanisms of antimicrobial resistance}; Hori S et al.; Most fundamental differences in the bacterial structure between the gram positive and negative bacteria are whether the organism has the outer membrane . The most essential mechanism of antimicrobial resistance in the gram negative bacteria are the alteration of membrane permeability to antibiotics . The outer membrane can perform as the barrier to prevent the cells from being exposed to antibiotics . On the other hand, the gram positive bacteria need to alternate the antimicrobial targets for reducing their binding affinity with antibiotics, because of defect of the outer membrane . On the basis of the structural difference between gram positive and negative bacteria, the mechanisms of bacterial resistance to beta-lactams, amino glycosides, macrolides, newer quinolones and vancomycin are discussed.

Cell Immunol, 1994 Feb, 153(2), 527 - 32
Arginine analogues suppress antigen-specific and -nonspecific T lymphocyte proliferation; Gregory SH et al.; Using analogues of arginine to inhibit nitric oxide (NO.) production, investigators have demonstrated the intermediary role of NO . in a variety of physiological events including the antimicrobial activity exhibited by macrophages in vitro . In an effort to establish the effector function of NO . in the antimicrobial activity expressed by macrophages in vivo, several groups report treating infected animals with relatively high concentrations of these same analogues . In the present study, we found that the arginine analogues NG-monomethyl-L-arginine, N omega-nitro-L-arginine methyl ester, aminoguanidine, and L-canavanine at concentrations > or = 10 mM significantly inhibited both the antigen-specific and -nonspecific proliferation of T lymphocytes in culture . These findings indicate that in vivo experiments demonstrating the suppressive effect of arginine analogues on host defenses are subject to alternative interpretations that do not directly involve the microbicidal activity of macrophages.

J Clin Epidemiol, 1994 Feb, 47(2), 147 - 56
Antibiotic misuse in diarrhea . A household survey in a Mexican community; Bojalil R et al.; A survey of 1659 households in a periurban community in Mexico City was carried out to assess the frequency of and risk factors for inappropriate antimicrobial therapy in acute diarrhea . The housewife was interviewed to obtain information of the occurrence of diarrhea or use of an antibiotic in the previous 2 weeks by any member of the family . An antibiotic was used in 37% or 287 diarrheal episodes although only in 5% of all episodes was this therapy indicated, based on the presence of gross blood in stools . Patients seen by a physician were 6 times more likely to be treated with an antibiotic compared to those who did not consult a physician (p < 0.001) . Self-medication was associated with a higher risk of using an inadequate drug or dose (in 72% of treated episodes) and of following treatment for less than 5 days (in 66% of treated episodes) . Other risk factors significantly and independently associated with antibiotic misuse were: an increased number of stools (odds ratio {OR} = 1.21; 95% confidence interval {CI} = 1.04, 1.41), bloody diarrhea (OR = 19.04; 95% CI = 2.52, 160.90) and family crowding (OR = 2.07; 95% CI = 1.17, 3.63) . These findings support future community-oriented educational interventions aimed at improving physician prescribing practices and patient compliance behavior in order to achieve a more rational use of antibiotics.

J Am Dent Assoc, 1994 Feb, 125(2), 163 - 9; discussion 169-71
Treating periodontal diseases by blocking tissue-destructive enzymes; Golub LM et al.; A new therapeutic approach involves the discovery by the "Stony Brook group," that tetracyclines, but not other antibiotics, can inhibit host-derived collagen-destructive enzymes . This newly discovered property of tetracyclines is unrelated to the antimicrobial activity of these drugs . Examples support the hypothesis that this unexpected property of tetracyclines provides a new approach to treating periodontal diseases as well as a variety of medical disorders.

Invest Ophthalmol Vis Sci, 1994 Feb, 35(2), 417 - 21
Secretion of group 2 phospholipase A2 by lacrimal glands; Nevalainen TJ et al.; PURPOSE . Tears are known to have antimicrobial properties . The authors investigated the presence of the antibacterial enzyme phospholipase A2 (PLA2) in tears and lacrimal glands . METHODS . The catalytic activity of PLA2 and the amount of pancreatic group 1 PLA2 and nonpancreatic group 2 PLA2 were measured in homogenates of eight human lacrimal glands from autopsied subjects and in tears from four healthy volunteers . The localization of PLA2s in lacrimal gland sections was studied by immunohistochemistry . Skeletal muscle was used as a control . RESULTS . The catalytic activity of PLA2 was significantly higher in lacrimal glands than in skeletal muscle . Immunochemical analysis showed significantly higher amounts of group 2 PLA2 in lacrimal gland than in skeletal muscle homogenates . Group 1 PLA2 was present in trace amounts only . The concentration of group 2 PLA2 in tears was high (1451.3 micrograms/l) compared to that in the serum of healthy individuals (3.7 micrograms/l) . By immunohistochemistry, a granular reaction of group 2 PLA2 was localized in the glandular cells of lacrimal glands . The apical cytoplasm of many duct cells also was labeled . CONCLUSIONS . The lacrimal glands secreted nonpancreatic group 2 PLA2, which most likely acts as an antiinfectious factor in tears.

J Chemother, 1994 Feb, 6(1), 29 - 34
Activity of antimicrobial drugs evaluated by agar dilution and radiometric methods against strains of Nocardia asteroides isolated in Italy from immunocompromised patients; Scopetti F et al.; Benzylpenicillin, amoxicillin, amoxicillin plus clavulanic acid, cephalothin, cephaloridine, cefotaxime, imipenem, erythromycin, clarithromycin, azithromycin, amikacin, ciprofloxacin and trimethoprim-sulfamethoxazole were tested in vitro by the agar dilution method against eleven strains of Nocardia asteroides isolated both from AIDS and other immunocompromised patients . Imipenem, amikacin and trimethoprim-sulfamethoxazole were shown to be the most active drugs with minimum inhibitory concentrations (MIC) values nearly always lower than concentrations achievable in blood . Ciprofloxacin, cephaloridine and cefotaxime were moderately active, while the remaining drugs were totally ineffective . When susceptibility was assessed by the radiometric method the MIC90 values were uniformly lower than those in the agar method, possibly due to lower inactivation of drugs during incubation . The two methods showed a good correlation only for imipenem, amikacin and ciprofloxacin . The results obtained by the radiometric method seem to indicate that, as for mycobacteria, this method may also give a more accurate evaluation of the antimicrobial susceptibility of Nocardiae.

Int Dent J, 1994 Feb, 44(1), 33 - 43
Oral mucosal disease: a decade of new entities, aetiologies and associations; Scully C et al.; New patterns of oral mucosal disease and indeed new disorders have been emerging over the past decade . Although infection with human immunodeficiency viruses (HIV) is having the most profound impact, there are also major changes in oral health and the standard of health care required, because of other new disorders and medical care . The increase in tissue transplantation, with the concomitant use of immunosuppression is resulting in a range of oral problems . Other iatrogenic oral diseases likely to increase include ulcers associated with cytotoxic chemotherapy; lichenoid eruptions related to drugs and restorative materials; and a multiplicity of other complications . Dilemmas are presented by some new disorders such as orofacial granulomatosis . No less are the difficulties presented by the now obvious heterogeneous nature of oral subepithelial vesiculobullous disorders . Finally, there are, even in these days of social medicine and antimicrobial availability, new infectious diseases emerging . Continued increases in population mobility; continued sexual promiscuity; and the development of new drugs are all likely to act to increase the spectrum of oral disorders seen.

Singapore Med J, 1994 Feb, 35(1), 108 - 9
Primary closure following drainage of a rectus sheath muscle abscess; Visvanathan R; The primary closure of a rectus sheath muscle abscess was performed on an 11-year-old child following evacuation of its contents under antimicrobial cover . Complete healing was achieved in eight days . This method avoids the delays in wound healing and morbidity associated with conventional drainage and shortens convalescence.

Int J Clin Pharmacol Ther, 1994 Feb, 32(2), 88 - 91
Evaluation of lung tissue and hilar lymph node concentrations of azithromycin; Cazzola M et al.; Since it is believed that most infections occur in the interstitial fluid, it has been suggested to measure the concentration of antimicrobial agents in pulmonary lymph that reflects the extracellular, extra-blood-vascular milieu in the lung . The aim of this study was to investigate the lung tissue and pulmonary lymph node penetration of azithromycin after 500 mg daily oral administration for three days in patients undergoing open thoracotomy . At the end of the treatment, each subject was assigned for 5 groups of 5 patients each according to thoracotomy time after the last dose (24, 48, 96, 120 and 144 h) . Azithromycin was assayed by an agar diffusion method with Sarcina lutea Z114 (DRH) used as the test organism and the Antibiotic Assay Medium 1, pH 8.5 used as the medium . All patients had a detectable concentration of azithromycin in serum 24 h after the last dose (72 h after the first dose); the concentration fell below the detection limit (0.01 mg/l-1) after 96 h (168 h after the first dose) . Peak concentrations in lung tissue and lymph nodes were found after 48 h (96 h after the first dose) . Tissue and lymph node concentrations of azithromycin were much greater than serum concentrations and these tissue and lymph node concentrations persisted after serum concentrations declined . The concentrations in lung tissue of azithromycin were always higher than corresponding concentrations in hilar lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Boll Chim Farm, 1994 Feb, 133(2), 72 - 5
Synthesis and antimicrobial evaluation of new derivatives of diphenylsulfone; de la Cruz A et al.; New derivatives of diphenylsulfone have been synthesized and their antibacterial and antifungal activities evaluated . Their chemical structures have been established by means of analytical and NMR spectroscopic data.

Farmaco, 1994 Feb, 49(2), 137 - 40
Synthesis and antimicrobial activity of new 3,5-diaminoisothiazole derivatives; Cocco MT et al.; The 3,5-diaminoisothiazole derivatives 23-42 were synthesized in excellent yields by oxidative cyclization of 3-amino-3-(dialkylamino)propenethioamide derivatives . These intermediates and the isothiazole derivatives were tested in vitro for their antimicrobial activity.

Antibiot Khimioter, 1994 Feb-Mar, 39(2-3), 52 - 6
{The use of clindamycin in the prevention and treatment of infectious complications in the cancer clinic}; Dmitrieva NV; Clindamycin used alone or in combination with other antimicrobial drugs such as aminoglycosides, dioxidin and fluoroquinolones in the prophylaxis and treatment of infectious complications in oncological patients was shown to be highly efficient . When clindamycin was used prophylactically in combination with netilmicin, the postoperative infectious complications developed in 3 out of 27 patients with tumors of the head and neck, in 1 out of 24 patients with tumors of the rectum and colon and in 3 out of 16 patients with tumors of the female genitalia . The clinical effect was observed in 36 (87.8 per cent) out of 41 patients with postoperative wound infections and in 38 (82.5 per cent) out of 40 patients with pneumonia . Therefore, the use of clindamycin alone or in combination with other antimicrobial drugs is essential in the treatment of infectious complications in oncological patients.

Arq Bras Cardiol, 1994 Feb, 62(2), 107 - 11
{Myocardial infarction in infective endocarditis}; Jorge Sdo C et al.; Two patients with chronic valvular heart disease and myocardial infarction were assisted at our hospital . Both of them were febrile and only one had petechiae associated with signs of valvular involvement led to suspicion of infective endocarditis . Although blood cultures were negative, echocardiographic, surgical and anatomopathologic findings were compatible with infective endocarditis . They required cardiac surgery during the acute phase of the infection because they presented progressive hemodynamic deterioration and no satisfactory response to antimicrobial regimen too . One patient died at late follow-up (two weeks after the hospital discharge) and the other survived, but with signs of cardiac failure (class II of NYHA) one year after the procedure.

J Hosp Infect, 1994 Feb, 26(2), 93 - 8
Evaluation of the optimal hand-scrub duration prior to total hip arthroplasty; O'Farrell DA et al.; Orthopaedic surgeons in many major arthroplasty centres advocate the use of a prolonged surgical hand-scrub prior to total joint replacement . In this study we evaluated the antimicrobial efficacy of a 5 compared with a 10 min scrub before both long (> 90 min) and short (< 90 min) operations for total hip arthroplasty . Surgical hand disinfection was performed on one occasion for 5 min and on a second for 10 min by 41 surgeons and theatre nurses using 4% chlorhexidine gluconate as a detergent formulation ('Hibiscrub', ICI Pharmaceuticals) . None of the subjects had previously scrubbed on the day of each test . Bacterial colony counts on the fingers were measured using the method described by Rotter (vide infra) before scrubbing, immediately after scrubbing, and at the end of each operation . Our results showed that for arthroplasty procedures lasting less than 90 min (35 operations) a 5 min hand-scrub was equally as effective as one of 10 min . However, following longer procedures (36 operations) colony counts were significantly higher on subjects who had scrubbed for 10 min than on those who only scrubbed for 5 (P < 0.05, Mann-Whitney U-Test) . This study suggests that the practice of a prolonged scrub before total joint replacement does not have a scientific basis and that such a policy should be discontinued where it is still practised.

J Assoc Physicians India, 1994 Feb, 42(2), 127 - 31
Non-responsiveness to antimicrobial therapy; Lele RD; During the course of treating patients the clinician is faced with the problem of non-response to drugs . The expected therapeutic benefit is not observed . The cause may lie in the diagnosis, sub-type of disease, in the resistance of invading micro-organism or the drug itself . The drug dose, frequency, duration, mode of administration, compliance may be inadequate, inappropriate; the patient's pharmacokinetic profile may be unexpected, unusual; there may be alteration in the receptor, population, type, compensatory mechanism of the body etc . The relative importance of the host, parasite and drug related factors varies with disease, type of patient and drug under consideration . In the second section of the Clinical Pharmacology series, the causes of non-responsiveness to drugs will be discussed with reference to a few common diseases . The principles are applicable to may others.

Lett Appl Microbiol, 1994 Feb, 18(2), 115 - 6
The antimicrobial activity of phenoxyethanol in vaccines; Lowe I et al.; The activity of the antimicrobial preservatives, phenoxyethanol and thiomersal, were compared in diphtheria, tetanus and pertussis (adsorbed) vaccine . Both chemicals were equally effective in inactivating challenge doses of Gram-negative and Gram-positive micro-organisms, as well as a yeast.

Hindustan Antibiot Bull, 1994 Feb-May, 36(1-2), 21 - 9
Preliminary studies on a Streptomyces sp . CS-14 showing broad spectrum antibiotic activity; Malviya HK et al.; A Streptomyces sp . CS-14 producing antifungal and antibacterial antibiotics has been isolated and characterized . The characterization of mycelial bound antibiotic revealed the presence of a hexaene polyene macrolide whereas filtrate bound antibiotic belonged to aminoglycoside group . Both the antibiotics showed very good antimicrobial activities in vitro.

J Leukoc Biol, 1994 Feb, 55(2), 227 - 33
Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages; Bogdan C et al.; Nitric oxide (NO) contributes to the antitumor, antimicrobial, and immunosuppressive activity of macrophages . An inducible form of NO synthase (iNOS) is responsible for high output generation of nitric oxide by macrophages after stimulation with cytokines and/or lipopolysaccharide (LPS) . In the present study, we demonstrate that interleukin 4 (IL-4) suppressed production of NO by primary mouse peritoneal macrophages exposed to IFN-gamma with or without LPS, even while synergizing with IFN-gamma to increase the secretion of TNF-alpha . Suppression of NO production was paralleled by decreases in iNOS enzyme activity and iNOS antigen . IL-4 did not inhibit induction of iNOS mRNA 4-6 h after exposure to IFN-gamma, but strongly reduced iNOS mRNA at later times of stimulation (24-72 h), without increasing its turnover . The conditions for maximal suppression of iNOS expression by IL-4 and the mechanisms of suppression differed from those determined in parallel for transforming growth-factor-beta as described elsewhere . These results illustrate the diversity of phenotypes of macrophages deactivated by different cytokines, and demonstrate that IL-4 has the potential to reduce one component of the anti-tumor, antimicrobial, and immunosuppressive activities of macrophages.

Mutat Res, 1994 Feb, 312(1), 33 - 7
Sister-chromatid exchange (SCE) and cell proliferation in lymphocytes from infected and non-infected children with severe protein calorie malnutrition (PCM); Ortiz R et al.; The frequency of sister-chromatid exchanges (SCE) and the rate of cell proliferation were evaluated through differential staining of sister chromatids in mitogen-stimulated cultured lymphocytes sampled from five well-nourished children, from seven severely malnourished children infected with bacterium, and from 10 severely malnourished children following treatment for infection with antimicrobial drugs 2 weeks before blood sampling . The replication indices at 48 h of culture were higher in both groups of malnourished children than in the well-nourished children, indicating either a faster response to PHA and/or a shorter cell cycle in lymphocytes of these patients . The average frequency of SCE per mitosis was also significantly higher than in the control group . The mitotic index was similar in the three groups of children . The lack of significant difference in response between the two groups of malnourished children suggests that the effects observed at the cytogenetic level are caused by severe malnutrition per se, and not by any associated infection.

Biochem Biophys Res Commun, 1994 Jan 28, 198(2), 510 - 5
Inducible L-arginine-dependent nitric oxide synthase activity in bovine bone marrow-derived macrophages; Adler H et al.; In rodent macrophages, cytokines or bacterial constituents induce a Ca(2+)-independent nitric oxide (NO) synthase which plays a key role in antimicrobial and tumoricidal activity . Firm evidence for expression of a similar enzyme in other mammals has been lacking . Here we show that bovine bone marrow-derived macrophages produce nitrite in an L-arginine-dependent manner upon stimulation with heat-killed gram-positive or gram-negative bacteria . NO2- production was markedly diminished by arginase, and by the arginine analogue, NG-monomethyl-L-arginine . Bacteria-induced NO2- production was enhanced by concomittant exposure to interferon-gamma, tumor necrosis factor-alpha or both combined, although these cytokines alone (in the absence of bacteria) induced little NO2- . This is one of the first demonstrations of NO2- production by non-rodent macrophages.

J Biol Chem, 1994 Jan 21, 269(3), 1934 - 9
The NH2-terminal alpha-helical domain 1-18 of dermaseptin is responsible for antimicrobial activity; Mor A et al.; Dermaseptin, a 34-amino acid residue cationic peptide, was recently shown to inhibit the growth of pathogenic fungi responsible for severe opportunistic infections accompanying immunodeficiency syndrome and the use of immunosuppressive agents . To improve our understanding of the mechanism by which dermaseptin exerts its potent antimicrobial action, a series of either NH2- or COOH-terminally truncated analogs was synthesized . These analogs were evaluated for their ability to inhibit the growth of various pathogenic agents in culture medium . Dermaseptin exerted a lytic action upon bacteria, protozoa, yeasts, and filamentous fungi at micromolar concentrations . No inhibition of proliferation was observed with human KB cells, and dermaseptin did not lyse guinea pig lymphocytes or rabbit erythrocytes at doses up to 200 micrograms/ml . Shortening the peptide chain of dermaseptin to dermaseptin-(3-34) slightly reduced the activity of the peptide, while further reduction of the chain length to residues 14-34, 16-34, 20-34, and 28-34 yielded peptide derivatives devoid of antimicrobial activity . On the other hand, lengthening the peptide chain starting from residues 1-4 to residues 1-8 and 1-18 led to a progressive recovery of the activity of the parent molecule . Whereas the central core of dermaseptin (residues 10-19) was virtually inactive, alteration of the COOH-terminal carboxylic group of dermaseptin-(1-18) to a carboxamide yielded a peptide exhibiting enhanced antimicrobial potency, yet displaying even less in vitro toxicity compared with dermaseptin . Overall, the data indicate that molecular elements responsible for the exceptional antimicrobial potency of dermaseptin are to be traced to the NH2-terminal alpha-helical amphipathic segment spanning residues 1-18 of the molecule . Dermaseptin-(1-18)-NH2 may therefore be considered as a useful and highly tractable tool for identifying key features responsible for membrane permeabilization and as a starting point for the design of new therapeutic agents.

Tidsskr Nor Laegeforen, 1994 Jan 20, 114(2), 169 - 73
{Use of antimicrobial agents in Norway 1980-92}; Andrew M et al.; Use of systemic antimicrobial agents in Norway shows a moderate increase from 1980 to 1992, from 13.5 to 16.9 defined daily doses (DDDs) per 1,000 inhabitants per day . Comparing the Nordic countries, the use of these drugs is second lowest in Norway, after Denmark . In relative terms the use of tetracyclines is highest in Norway . Use of co-trimoxazole is also relatively high, while use of macrolides is low . The share of penicillin V and G is highest in Sweden . Several new and important antimicrobial agents have been introduced on the Norwegian market during the period, while almost as many have been withdrawn . Penicillin V and G constitutes the main subgroup . However, the use of tetracyclines is almost as high, for a short period in fact higher . Taking into account the development of drug resistance and adverse events, it is recommended that use of tetracyclines and co-trimoxazole be reduced, mainly to the advantage of penicillins . The use of cephalosporins seems to be reasonable, but penicillins should be considered more often as an alternative . The use of antimycotic and antiviral drugs is low in terms of DDDs . In 1992 the cost of antimicrobial agents for systemic use was in 1992 approx . NOK 400 million, retail price . The largest subgroup, cephalosporins, constituted almost 20%, as against only 2% of DDDs . Antimicrobial agents represent a substantial part of the total drug budget in hospitals . A shift from expensive to cheaper alternatives should be considered as a routine . Moreover, an optimal change from parenteral to oral administration could help to reduce costs.

Eisei Shikenjo Hokoku, 1994, (112), 206 - 8
{On the revision of microbial tests in the Pharmacopoeia of Japan}; Mise K; Revision of microbial tests in the Pharmacopoeia of Japan has been in progress since 1992 . The affected areas include sterility tests, microbial limit tests, antimicrobial preservatives-effectiveness, and methods for strilization . Here, the revision of sterility tests, as well as of microbial limit tests, is discussed in detail . Several problems in JPXII are also described.

J Appl Biomater, 1994 Winter, 5(4), 325 - 31
Ciprofloxacin attachment to porous-coated titanium surfaces; Dunn DS et al.; A simple and effective method for attaching ciprofloxacin HCl salt to the surface of porous-coated titanium based orthopedic materials was developed . The method utilizes the electrophoretic migration of both fine ciprofloxacin HCl particles and ciprofloxacin ions to deposit the antibiotic salt on a positively biased surface . The quantity of antibiotic deposited can be easily and effectively controlled by varying the time of deposition and applied voltage . In vitro tests have indicated that the antimicrobial activity of the treated surfaces is retained for a period of 5 days . The method allows a significant amount of antibiotic to be deposited and could theoretically be used to deliver antibiotics to the tissues surrounding prosthetic devices in order to prevent postoperative infections.

Chemotherapy, 1994 Jan-Feb, 40(1), 65 - 9
Single-dose antibiotic prophylaxis in maxillofacial surgery; Hotz G et al.; The clinical efficacy of short-term antimicrobial prophylaxis with either one shot of ceftriaxone (1 g) or a course of 3 injections of a fixed combination of mezlocillin (2 g) and oxacillin (1 g) administered over 24 h was studied in a prospective randomized clinical study of 100 patients undergoing elective maxillofacial surgery . Tissue and plasma concentrations of the antibiotics were determined by high-pressure liquid chromatography in 6 tumor surgery patients from each treatment group . Statistical analysis showed the treatment group to be comparable both demographically and with respect to the types of surgery performed and the durations of the procedures . Only 1 patient in each group developed a postoperative wound infection . It is concluded that 1 g ceftriaxone given 30 min preoperatively meets the pharmacokinetic requirements for perioperative antimicrobial prophylaxis in maxillofacial surgery.

Ann Otol Rhinol Laryngol, 1994 Jan, 103(1), 54 - 8
Does topical antibiotic prophylaxis reduce post-tympanostomy tube otorrhea?
Garcia P, Gates GA, Schechtman KB.
Purulent otorrhea is the most common complication of tympanostomy tube (TT) insertion . It may occur in the postoperative period or at any time during the sojourn of the tube . The efficacy of topical antimicrobial prophylaxis against purulent postoperative otorrhea (PPO) has been examined in 5 prospective, randomized studies; all demonstrated a reduction in PPO from topical antimicrobial prophylaxis, but in only 1 study was the difference statistically significant . Because the 5 studies used 2 different experimental designs--by-patient, and by-ear--a single meta-analysis could not be done . However, the by-patient studies met the criteria for meta-analysis, which demonstrated a combined odds ratio of 0.12 (95% confidence interval 0.04 to 0.37, p = .0002) . This represents an 85% reduction in otorrhea, which is judged to be clinically as well as statistically significant . We conclude from the available evidence that prophylactic use of topical antimicrobial agents following TT insertion consistently reduces the rate of PPO . However, the low incidence of PPO and the heterogeneity of the published studies prevent making a final judgment for or against the continued use of these agents . Therefore, given that these potentially ototoxic agents are frequently administered to prevent postoperative otorrhea, further study of this subject is warranted . In the meantime, we recommend judicious use of these agents following TT insertion in those cases at higher risk for PPO, namely those with mucoid or purulent effusion.

Am J Med Sci, 1994 Jan, 307(1), 64 - 75
Southwestern Internal Medicine Conference: brucellosis: don't let it get your goat!
Radolf JD.
Brucellosis is a highly pleomorphic zoonotic infection caused by one of the following four species of gram-negative facultative intracellular coccobacilli: Brucella melitensis, B . abortus, B . suis, or B . canis . The disease is a worldwide public health problem and a significant cause of economic losses in domestic live-stock . Although largely eradicated in most industrialized countries, in the United States there has been an upsurge of B . melitensis cases associated with the ingestion of unpasteurized goat's milk or goat's milk cheese from Mexico . Brucellosis can be either insidious or abrupt in onset and can affect virtually every organ system; skeletal involvement (spondylitis, arthritis) is the most frequent metastatic complication . Cases are diagnosed either by isolation of the bacterium (usually from blood) or by serologic testing . Treatment of brucellosis requires the administration of two antimicrobial agents . Doxycycline plus streptomycin or rifampin or trimethoprim-sulfamethoxazole plus rifampin appear to be the most effective regimens.

J Leukoc Biol, 1994 Jan, 55(1), 81 - 90
Interleukin-2 suppresses activated macrophage intracellular killing activity by inducing macrophages to secrete TGF-beta; Nelson BJ et al.; Phorbol myristate acetate (PMA) treatment of an EL-4 thymoma cell line (EL-4FARRAR) induced secretion of a factor that inhibited intracellular killing of Leishmania major amastigotes by activated macrophages . Analysis of the cytokines produced by EL-4 cells after PMA stimulation identified interleukin-2 (IL-2, 2500 U/ml), IL-4 (1280 U/ml), interferon-gamma (IFN-gamma; 100 U/ml), and granulocyte-macrophage colony-stimulating factor (GM-CSF; 50 U/ml) . Neither tumor necrosis factor nor transforming growth factor beta (TGF-beta) was detected . Each of the cytokines present in EL-4 fluids was assessed for capacity to activate macrophages for destruction of parasites or to suppress intracellular killing . IFN-gamma and GM-CSF both activated macrophages to kill Leishmania; IL-2 and IL-4 had no activity for induction of this antimicrobial effector function . IL-2 and IL-4 were tested for their capacity to inhibit lymphokine- or IFN-gamma-induced destruction of L . major by macrophages: IL-4 was ineffective, but IL-2 markedly suppressed the activation of macrophages for intracellular killing . Addition of > or = 10 U/ml of IL-2 at the time of infection, or up to 4 h before, blocked up to 100% of the capacity of activated macrophages to kill intracellular amastigotes . Immunoaffinity treatment of EL-4 fluids with anti-IL-2 antibody resulted in > 80% reduction in suppression of intracellular killing . The suppressive effects of IL-2 were not direct, but mediated by TGF-beta . IL-2 induced resident peritoneal macrophages to secrete > 5000 pg/ml TGF-beta 1, a quantity that is > 500-fold higher than constitutive background levels (20-40 pg/ml) and is sufficient to block intracellular killing activities . This increase in secretion of TGF-beta was not dependent increases in TGF-beta 1 mRNA . Treatment of cultures with EL-4 fluids or recombinant IL-2 in the presence of antibody to TGF-beta 1 blocked the suppressive activity of both . Thus, IL-2 was the major suppressor factor in EL-4 fluids, and it acted indirectly through the induction and autocrine action of TGF-beta.

Blood, 1994 Jan 1, 83(1), 152 - 60
Effect of human recombinant cytokines on the induction of macrophage procoagulant activity; Schwager I et al.; A panel of human recombinant cytokines was tested for induction of procoagulant activity (PCA) in human monocyte-derived macrophages . Nonadherent culture conditions were used, and PCA was determined with whole cells rather than cell lysates . It was assured by Limulus amebocyte lysate assay that tested cytokines displayed low levels of endotoxin activity within the range of biologic activity . Additional evidence to rule out an endotoxin effect was provided by heat-inactivation experiments . Interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) were strong macrophage PCA inducers . The low level of PCA induced by IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, IL-4, IL-6, IL-10, and IFN-alpha could not be distinguished from that induced by traces of endotoxin contaminating the preparations . Transforming growth factor-beta decreased constitutively expressed PCA within 24 hours of exposure . PCA induced by IFN-gamma, IL-1 beta, and TNF-alpha depended largely on tissue factor expression, as evidenced by experiments with factor X-deficient plasma and antitissue factor antibodies . In macrophages subcultured in adherence, IL-1 beta was a strong PCA inducer, whereas IFN-gamma and TNF-alpha promoted little PCA increase . This observation and different kinetics of PCA induction suggested that mechanisms of PCA induction are distinct for the three cytokines . Thus, we showed that well-characterized cytokines critically involved in the promotion of cell-mediated antimicrobial defense/delayed-type hypersensitivity and considered for clinical application promote local fibrin deposition by a direct effect on macrophages.

J Immunol, 1994 Jan 1, 152(1), 231 - 40
A novel granulocyte-derived peptide with lipopolysaccharide-neutralizing activity; Larrick JW et al.; Rabbit CAP18 (cationic antimicrobial protein, 18 kDa) is a leukocyte protein identified and purified using as an assay its capacity to bind and inhibit various activities of LPS . Oligonucleotide probes designed from the putative N-terminal protein sequence were used to obtain the corresponding cDNA from a rabbit bone marrow cDNA library . Examination of the cDNA sequence revealed that the protein fragment of the putative N-terminus was actually a 37-amino-acid C-terminal fragment . This fragment, designated CAP18(106-142), inhibits many activities of LPS . In the present studies, synthetic CAP18(106-142) is shown to: 1) bind to erythrocytes coated with diverse strains of LPS; 2) inhibit LPS-induced release of cytokines (TNF, IL-1, IL-6) and nitric oxide from macrophages; 3) inhibit LPS-induced LAL coagulation and 4) protect mice from LPS lethality . CAP18(106-142) may have therapeutic utility for conditions associated with elevated concentrations of LPS.

Immunol Ser, 1994, 60, 363 - 80
Macrophages and Brucella; Baldwin CL et al.; The studies reviewed here indicate that during the course of infection with B . abortus protective immune responses occur and that macrophages are activated for antimicrobial activity in both susceptible and resistant animals . Yet in susceptible animals chronic infections with B . abortus become established . There is circumstantial evidence from experiments in vitro that the outcome of infection is related to macrophage/Brucella interactions . This includes the following: 1) the virulence of strains of B . abortus is proportional to their ability to inhibit host phagocyte functions and to survive in murine, bovine, and guinea pig macrophages; and 2) the ability of guinea pig and bovine macrophages to inhibit intracellular growth of brucellae is directly proportional to the innate resistance of the host from which the macrophages were derived . In the murine model, the relative resistance of C57Bl/10 mice to infection with virulent B . abortus strain 2308 correlated with more efficient clearance during the first week following infection, compared with the susceptible BALB/c strain . It is not known whether this was due to innate differences in the recruitment or bactericidal activities of macrophage populations in the two mouse strains, as demonstrated with L . monocytogenes, or to other nonimmune factors such as natural killer cells secreting IFN-gamma and lysing infected macrophages following direct interaction with the brucellae, as shown with other intracellular bacteria . It is also of interest that clearance of strain 2308 following the plateau phase was slower in BALB/c than in C57Bl/10 mice . Since at this time protective T cells are known to be present in the spleens of BALB/c mice, this difference may have been due either to more efficient clearance of brucellae by C57Bl/10 macrophages following activation with T cell cytokines, or to the inability of immune T cells to interact with Brucella-infected macrophages in the susceptible BALB/c strain . CD8 T cells have been shown to have an important role in clearance of brucellae following the peak of infection and may act by lysing chronically infected macrophages . Although protective T cells have been demonstrated in susceptible strains of mice, chronically infected macrophages in these animals may fail to act as targets or may down-regulate T cell functions . As a result, infected macrophages could persist in the presence of Brucella-specific T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunol Ser, 1994, 60, 29 - 46
Macrophage activation: a riddle of immunological resistance; Crawford RM et al.; Various lines of defense against infection are present in all living creatures . The balance between symbiosis and parasitism is determined by the mechanisms through which the host resists infection and by the extent of injury induced by the parasite: both factors contribute to disease . Lines of host defense can be arbitrarily divided into three components: 1) barrier functions of skin and mucous membranes and their innate physical and secretory antimicrobial components; 2) elements of host defense that do not necessarily require prior exposure to an infectious agent or immunologic memory (mast cells, granulocytes, macrophages, NK cells, gamma/delta T cells); and 3) immune responses directed against specific epitopes on the infectious agent induced by prior exposure and immunologic memory (alpha/beta T cells, B cells) . Analysis of such host defense mechanisms repeatedly documents tremendous redundancy and overlap between these lines of defense . Further, there is open communication, so that a change at any one level ripples throughout the system . Acquired nonspecific resistance to infection is an example of such a ripple . Host response to one infection alerts the immune system, so that the general level of resistance to other infectious agents is increased . This response is initiated by an immune response (third line of defense) but effected by nonspecific elements (second line of defense) . The survival value of such responses is obvious . There are numerous examples in both mouse and man of the operation of these systems in response to infection . Further, the menus of antimicrobial components available to both mouse and man for resistance to infection are very similar, but not identical . Indeed, it is said that the genetic basis for differences between mice and man revolve around a difference of less than 10% in DNA sequences . But there are differences! Mouse macrophages produce IFN-beta in response to infection, human cells produce IFN-alpha . Mouse macrophages effect antimicrobial activity principally through induction of NO synthase and the generation of toxic nitrogen oxides . This pathway has yet to be described with human macrophages . In both man and mouse, F . tularensis is an obligate intracellular parasite of macrophages that requires an essential component provided by the cell for its replication . That mouse and man are not so different is well illustrated by the effector mechanisms induced by IFN-gamma for antimicrobial activity against F . tularensis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adv Exp Med Biol, 1994, 349, 97 - 105
Established antimicrobial susceptibility testing methods with a new twist--points to consider and a glimpse of the future; Walsh LR; The developments seen in these systems allow speculation about future trends in antimicrobial susceptibility testing methods . Microbiology system manufacturers seem to be heeding the call of all industry, for greater automation, enhanced data management capabilities and increased flexibility (see Table 2 below) . {table: see text} Cost seems to be less of an issue . This may be due to the decrease in the availability of medical technologists and the need to find systems with better throughput and increased productivity . Increased automation, data management capabilities, and walkaway technology may justify the additional cost of some of these systems . The computer software package provided with these systems is becoming increasingly important with the focus on quality assurance and utilization . Computer generated data analysis gives the microbiologist the tools to educate physicians through the use of selective reporting functions, antibiograms, cost analysis and drug effectiveness comparisons . Each of the four systems is unique and will probably find a niche among the various markets that exist in the United States, European and other specialized markets . The lack of automation in the ALAMAR system may be its selling point in those areas where automation is not affordable, but new ways are being sought for ease of interpretation of results . BIOMIC and CATHRA systems may be more beneficial to those microbiologists who do not want to stop doing traditional Bauer-Kirby or agar dilution methods, but require computer enhancements . ALADIN, may fill a niche to which other walkaway systems have not adapted, but because of its expense, will face more demands than the other three systems covered in this review.

J Ethnopharmacol, 1994 Jan, 41(1-2), 115 - 9
Antimicrobial activity of Visnea mocanera leaf extracts; Hernandez-Perez M et al.; A chemical study of Visnea mocanera leaves was carried out giving lupeol and beta-sitosterol fatty esters, as well as beta-sitosterol and the triterpenic betulinic, ursolic, platanic and 2 alpha,3 beta-dihydroxy-ursan-12-en-28-oic and 2 alpha,3 beta-dihydroxy-olean-12-en-28-oic acids . Studies of the antimicrobial activity of acetone and methanol extracts as well as an aqueous infusion were also performed and the good experimental results obtained justify the folk use of this species as a cicatrizant and vulnerary agent.

Microbios, 1994, 77(310), 7 - 13
Antimicrobial activity of natural and semisynthetic diterpenoids from Sideritis spp; Rodriguez-Linde ME et al.; The antimicrobial activity of 22 natural diterpenoids of endemic Sideritis from Eastern Andalusia (Spain) is described . Only ent-kaur-16-ene foliol and ent-beyer-15-ene isopusillatriol proved to be active towards Gram-positive and acid-fast bacteria . The introduction of a ketonic group at C-15 on ent-kaur-16-enic systems produced a remarkable degree of activity.

Lab Anim, 1994 Jan, 28(1), 13 - 8
Guidelines for the welfare of animals in rodent protection tests . A report from the Rodent Protection Test Working Party; Effects of cefpirome in comparison with cefuroxime against human polymorphonuclear leucocytes in vitro; Department of Microbiology, Faculty of Medicine, Badajoz, SpainThe interaction of cefpirome and cefuroxime, with human polymorphonuclear leucocytes (PMNs) was examined . The effects of therapeutic concentration (1, 10, and 50 mg/L) of both antimicrobial agents on the adherence, spontaneous mobility, chemotaxis, chemokinesis, phagocytosis and candidacidal capacity were studied in vitro . No statistically significant variations, in relation to the control, were observed in the ability of PMNs to adhere to nylon fibre at the concentrations of cefuroxime and cefpirome used . With both antimicrobial agents, PMN mobility increased as the antibiotic concentration was increased . A statistically significant increase (P < 0.05) in spontaneous mobility, chemotaxis and chemokinesis was observed with cefpirome at only 10 mg/L . However, only spontaneous mobility was increased significantly with cefuroxime at 10 mg/L . The strongest effects were observed with cefpirome at 50 mg/L with variations of about 70% (P < 0.01), in chemotaxis and chemokinesis . In general, cefpirome had a positive effect on phagocytosis and candidacidal power, which was significant at a concentration of 50 mg/L (P < 0.01) . Cefuroxime, in general, produced no modifications in either phagocytosis or candidacidal power.

Res Vet Sci, 1994 Jan, 56(1), 62 - 8
Anti-inflammatory ketoprofen in the treatment of field cases of bovine mastitis; Shpigel NY et al.; The efficacy of ketoprofen in the treatment of acute clinical mastitis was evaluated in a clinical trial comprising a non-blind controlled study and a blind, placebo-controlled study . All the cows were treated with 20 g sulphadiazine and 4 g trimethoprim intramuscularly upon diagnosis, and half the dosage was given once daily thereafter . In addition, the ketoprofen treatment groups received 2 g ketoprofen intramuscularly once daily for the duration of the antimicrobial therapy . Recovery rates for the non-blind contemporary controls and the blind placebo-controls were 83.7 per cent and 70.7 per cent, respectively . In the non-blind controlled ketoprofen and the placebo-controlled ketoprofen treatment groups, recovery rates were 94.7 per cent and 92.3 per cent, respectively . The odds ratio (OR) of recovery was significantly (P < or = 0.01) high in the placebo-controlled study (OR = 6.75, confidence interval {CI} = 1.45 to 31.4), and high but not significant in the non-blind controlled study (OR = 2.64, CI = 0.53 to 13.10) . It was concluded that ketoprofen significantly improved recovery in clinical mastitis in dairy cows.

Transgenic Res, 1994 Jan, 3(1), 36 - 42
Expression of human lysozyme mRNA in the mammary gland of transgenic mice; Maga EA et al.; Owing to its inherent antimicrobial effect and positive charge, the expression of human lysozyme in bovine milk could be beneficial by altering the overall microbial level and the functional and physical properties of the milk . We have used transgenic mice as model systems to evaluate the expression of human lysozyme containing fusion gene constructs in the mammary gland . Expression of human lysozyme was targeted to the mammary gland by using the 5' promoter elements of either the bovine beta (line B mice) or alpha s1 (line H mice) casein genes coupled to the cDNA for human lysozyme . Expression of human lysozyme mRNA was not found in mammary tissue from any of line B mice . Tissues were analysed from six lines of H mice and two, H6 and H5, were found to express human lysozyme mRNA in the mammary gland at 42% and 116%, respectively, of the levels of the endogenous mouse whey acidic protein gene . At peak lactation, female mice homozygous for the H5 and H6 transgene have approximately twice the amount of mRNA encoding human lysozyme as hemizygous animals . Expression levels of human lysozyme mRNA in the mammary gland at time points representing late pregnancy, early, peak and late lactation corresponded to the profile of casein gene expression . Human lysozyme mRNA expression was not observed in transgenic males, virgin females or in the kidney, liver, spleen or brain of lactating females . A very low level of expression of human lysozyme mRNA was observed in the salivary gland of line H5.

Antimicrob Agents Chemother, 1994 Jan, 38(1), 142 - 3
Antimicrobial susceptibility of Arcanobacterium haemolyticum; Carlson P et al.; The susceptibilities of 138 clinical isolates of Arcanobacterium haemolyticum to 11 antimicrobial agents were tested . All strains were susceptible to phenoxymethylpenicillin, cephalosporins, erythromycin, azithromycin, clindamycin, vancomycin, doxycycline, and ciprofloxacin but were resistant to trimethoprim-sulfamethoxazole.

Antimicrob Agents Chemother, 1994 Jan, 38(1), 134 - 7
In vitro susceptibilities of rapidly growing mycobacteria to newer antimicrobial agents; Khardori N et al.; The in vitro antimicrobial susceptibilities of 42 isolates of rapidly growing mycobacteria (Mycobacterium fortuitum, M . chelonae, and Mycobacterium species {other than M . fortuitum and M . chelonae}) to nine quinolones, including newer agents, two new aminoglycosides, and an aminocyclitol (trospectomycin) were determined by a broth microdilution method . The new quinolones, PD 117596, PD 127391, and PD 117558, showed excellent in vitro activities against M . fortuitum (MICs for 90% of isolates {MIC90s}, 0.06, 0.06, and 0.12 microgram/ml, respectively) . The MIC90 of ciprofloxacin for M . fortuitum was 0.5 microgram/ml . Only 14 to 28% of isolates of M . chelonae were susceptible to various quinolones . Most isolates of all three species were susceptible to the new aminoglycosides SCH 21420 and SCH 22591 . The MIC90s of trospectomycin were 8 micrograms/ml for M . chelonae, 32 micrograms/ml for Mycobacterium species, and > 64 micrograms/ml for M . fortuitum.

Vet Pathol, 1994 Jan, 31(1), 28 - 36
Gastrointestinal aspergillosis and zygomycosis of cattle; Jensen HE et al.; Gastrointestinal mycosis was diagnosed in 73 lesions of 32 cattle without a history of engorgement, and tissues of 29 animals were examined histopathologically . The omasum was the target organ for infection, followed by the rumen and reticulum . Acute necrohemorrhagic lesions dominated, with infiltration of neutrophils and thrombosis . The etiologic diagnosis was accomplished by indirect immunohistochemical staining of fungal elements with a panel of mono- and polyclonal antibodies raised against fungal antigens . Aspergillosis and zygomycosis were diagnosed in one or more organs of 11 (34.4%) and 20 (62.5%) cattle, respectively, and dual infections were found in three lesions of two animals . Candidosis was diagnosed in only one case . Hematogenous spread of fungi predominantly to the liver was seen in nine animals . Lymphogenic spread of aspergilli to mesenteric and omasal lymph nodes occurred in one and two animals, respectively . Factors that seemed to predispose to mycotic infection included presence of other diseases and intense antimicrobial therapy . These factors and post-partum status, which included 23 of 29 (79.3%) cows, predisposed to mycosis in several ways, e.g., reflux of acidic abomasal contents into the forestomachs, stasis of proventricular content, metabolic dysfunctions, and stress.

J Pharm Sci, 1994 Jan, 83(1), 42 - 5
Measurement of temafloxacin in human scalp hair as an index of drug exposure; Uematsu T et al.; Scalp hair samples were obtained at 1-month intervals up to 3 months from healthy male volunteers participating in a phase I study of a new antimicrobial quinolone, temafloxacin . Hair was sectioned into 1-cm lengths from the scalp end . After corresponding portions from 10 pieces of hair were dissolved in 1 N NaOH, temafloxacin was extracted by chloroform and measured by HPLC equipped with fluorescence detection (excitation and detection wavelengths, 280 and 460 nm, respectively) . In all subjects taking a single oral dose (600 mg; n = 6) or repeated oral doses (900 mg/day, b.i.d., for 6.5 days; total, 5850 mg; n = 6), the drug was detected in hair . The 1-cm length of hair, in which temafloxacin was peaked, was shown to move at the rate of 1 to 1.3 cm/month when the hair of growing stage was analyzed . The largest sum of the concentrations of temafloxacin found in any set of measurements in hair in each subject was 31.7 +/- 15.0 (mean +/- SD, n = 6) and 226.3 +/- 99.4 ng/mg hair (n = 6) for the single and repeated doses, respectively . The drug concentration in hair increased by a factor of 7.1, whereas the ratios between the single and repeated doses were 9.8, 1.3, and 10.7 for the total given dose, observed maximal plasma concentration (Cmax), and area under the plasma concentration curve, respectively . It was obvious that the Cmax was the least likely factor determining temafloxacin concentration in hair.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Pept Protein Res, 1994 Jan, 43(1), 10 - 8
Theoretical conformational analysis and synthesis of analogues of the heptapeptide antibiotic K-582 A; De Coen JL et al.; A detailed theoretical conformational analysis of the linear heptapeptide antibiotic {Arg2}K-582 A (Arg-Arg-D-Orn-Thr-D-Orn-Lys-D-Tyr) was carried out . The results of the computer simulation suggest that the linear peptide has a high propensity to fold in solution into a quasi-cyclic conformation in equilibrium with pi(L-D) helices . The synthesis of two inactive analogues with an L-Lys in place of D-Orn3 or D-Orn5 confirms the importance of the proposed folding pattern for the occurrence of the antimicrobial activity of K-582 A.

Am J Hosp Pharm, 1994 Jan 1, 51(1), 79 - 84
Accuracy of penicillin allergy reporting; Preston SL et al.; The consistency of penicillin allergy documentation in the patient chart, pharmacy profile, and medication administration record was assessed, along with the correctness of the self-reported patient history of penicillin allergy . One hundred fifty adult inpatients with a reported penicillin allergy were interviewed about their allergy . Questions included length of time since the allergic reaction, symptoms of the reaction, and whether rechallenge was ever attempted . Patients were classified into categories of (1) more severe allergy, (2) less severe allergy, or (3) intolerance on the basis of results of the interview . The patient pharmacy profile, chart, and medication administration record were reviewed to determine whether the allergy label was present . Patients who received antimicrobials during their hospitalization were evaluated . Of 117 patients, 82.9% were classified as allergic and 17.1% as intolerant . The allergy was documented in 98.7% of patient charts and 96.7% of medication administration records . The symptoms of the allergic reaction were described in the chart for only 34% of patients . Agents substituted for penicillin were potentially more toxic in 70.4% of cases, equally effective in all cases, and more costly in 55.5% of cases . Most, but not all, patients labeled as penicillin allergic had a history consistent with an allergy to the drug . Pharmacists can help ensure accurate allergy documentation by evaluating patients and educating both patients and health care professionals.

J Periodontol, 1994 Jan, 65(1), 30 - 6
Short-term microbiological and clinical effects of subgingival irrigation with an antimicrobial mouthrinse; Fine JB et al.; Fifty chronic adult periodontitis patients completed a 6-week controlled, double-blind, split mouth clinical study to determine the effects of subgingival irrigation with an antimicrobial mouthrinse on periodontal microflora, supragingival plaque, and gingivitis when used as an adjunct to normal oral hygiene . Qualifying subjects had at least four sites, two on each side of the mouth, with probing depths between 4 and 6 mm, which bled on gentle probing . Following baseline examinations, subjects received a half mouth scaling and prophylaxis and full mouth subgingival irrigation with either the antimicrobial mouthrinse or sterile colored water control professionally delivered . Subjects continued irrigation at home once daily for 42 days with their assigned rinse delivered via a subgingival delivery system . All sites in the mouth were scored at baseline and at day 42 for supragingival plaque, bleeding on probing, and redness . For the four selected periodontitis sites, probing depth and attachment level were measured at baseline and on day 42; additionally, supragingival plaque and gingival redness were scored on days 7 and 21 . Subgingival plaque samples for microbiological analysis were harvested from the selected periodontal sites at baseline and on days 7, 21, and 42 . Microbiologically, irrigation with the antimicrobial mouthrinse resulted in statistically significant reductions compared to control in putative periodontopathogens, including black pigmenting species, which persisted at 42 days . Clinically, subgingival irrigation with the antimicrobial mouthrinse produced a significant reduction in supragingival plaque (P < 0.001), bleeding on probing (P = 0.019), and redness (P = 0.017) compared to the control, whether or not the area irrigated received a prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Bull World Health Organ, 1994, 72(1), 113 - 8
Clinical signs of pneumonia in children attending a hospital outpatient department in Lesotho; Redd SC et al.; To determine the value of clinical findings for the diagnosis of pneumonia, we evaluated 950 children who presented with respiratory illness to the outpatient department of the Queen Elizabeth II Hospital, Maseru, Lesotho . Those children at high risk for pneumonia and a systematically selected 20% sample of children at low risk were examined in turn by a nurse, a general practitioner, and a paediatrician; a chest radiograph was recorded for each child . Pneumonia was defined as radiographic findings compatible with the disease as interpreted by a paediatric radiologist . A respiratory rate > or = 50 breaths/minute was a sensitive sign for pneumonia among infants (sensitivity range for the three examiners: 59-79%), but identified a progressively smaller proportion of children with pneumonia in older age groups . Adjusting the respiratory rate for age using a threshold of > or = 40 breaths/minute for children aged > or = 12 months improved the sensitivity, but identified < 30% of children with pneumonia aged > or = 24 months . No drop in sensitivity with age was found when respiratory rate thresholds were evaluated for children with more severe radiographic evidence of pneumoniaPIP: Acute respiratory infections (ARI) are the root cause of more than 4 million child deaths annually . While the timely delivery of the full course of immunization does much to thwart ARI mortality, many children still contract pneumonia and need to be treated with antimicrobial drugs . Proper case management, however, depends upon whether pneumonia is accurately and timely diagnosed . The authors assess the value of clinical findings for the diagnosis of pneumonia from evaluations of 950 children presenting with respiratory illness to the outpatient department of the Queen Elizabeth II Hospital in Maseru, Lesotho . Findings obtained by a nurse, a general practitioner, and a pediatrician are also compared to shed light upon the relative values of their respective observations . Children at high risk for pneumonia were examined along with those in a systematically selected 20% sample of children at low risk . A chest radiograph was recorded for each child . Pneumonia was defined as a condition represented in the radiographic findings compatible with the disease as interpreted by a pediatric radiologist . The study found a respiratory rate of more than or equal to 50 breaths/minute to be a sensitive sign for pneumonia in infants; sensitivity among the examiners was in the range of 59-79% . Sensitivity did, however, increase for children aged 12 months or older when the respiratory rate was adjusted for age using a threshold of more than or equal to 40 breaths/minute, but less than 30% of children aged 24 months or older with pneumonia were identified . No decline in sensitivity with age was observed when respiratory rate thresholds were evaluated for children with more severe radiographic evidence of pneumonia . The authors therefore conclude that a respiratory rate thresholds of 50 breaths/minute may suffice to identify children with severe pneumonia . Sensitivity can always be increased by using an age-adjusted respiratory rate threshold .

New Microbiol, 1994 Jan, 17(1), 65 - 8
Inhibition of F'lac transfer by various antibacterial drugs in Escherichia coli; Debbia EA et al.; Several antimicrobial agents including mitomycin C and molecules belonging to the 4-quinolone, aminoglycoside and beta-lactam groups inhibited plasmid transfer to a varying extent, in actively growing Escherichia coli . In contrast, the same antibiotics did not prevent effective conjugation in nongrowing bacteria with the exception of mitomycin C . These results indicate that the drugs inhibit plasmid transfer by interfering with bacterial host functions rather than by recognizing a specific plasmid-mediated target . Several drugs are therefore capable, in principle, of reducing the spread of plasmid-mediated antibiotic resistance.

Crit Care Med, 1994 Jan, 22(1), 12 - 21
Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial . The IL-1RA Sepsis Syndrome Study Group; Fisher CJ Jr et al.; OBJECTIVES: To evaluate the safety, pharmacokinetics, and efficacy of human recombinant interleukin-1 receptor antagonist (IL-1ra) in the treatment of patients with sepsis syndrome . DESIGN: Prospective, open-label, placebo-controlled, phase II, multicenter clinical trial using three different doses of human recombinant IL-1ra . SETTING: Twelve academic medical center intensive care units in the United States . PATIENTS: Ninety-nine patients with sepsis syndrome or septic shock who received standard supportive care and antimicrobial therapy, in addition to infusion with escalating doses of IL-1ra or placebo . INTERVENTIONS: Patients received an intravenous loading dose of either human recombinant IL-1ra (100 mg) or placebo, followed by a 72-hr intravenous infusion of either one of three doses of IL-1ra (17, 67, or 133 mg/hr) or placebo . All patients were evaluated for 28-day, all-cause mortality . MEASUREMENTS AND MAIN RESULTS: A dose-dependent, 28-day survival benefit was associated with IL-1ra treatment (p = .015), as indicated by the following mortality rates: 11 (44%) deaths among 25 placebo patients; eight (32%) deaths among 25 patients receiving IL-1ra 17 mg/hr; six (25%) deaths among 24 patients receiving IL-1ra 67 mg/hr; and four (16%) deaths among 25 patients receiving IL-1ra 133 mg/hr . A dose-related survival benefit was observed with infusion of IL-1ra in patients with septic shock at study entry (n = 65; p = .002) and in patients with Gram-negative infection (n = 45; p = .04) . Patients with an increased circulating interleukin-6 (IL-6) concentration of > 100 pg/mL at study entry demonstrated a dose-related survival benefit with IL-1ra treatment (p = .009) . In patients with an increased IL-6 concentration at study entry, the magnitude of the decrease in IL-6 concentration 24 hrs after the initiation of therapy was correlated with increasing the IL-1ra treatment dose (p = .052) . A significant dose-related reduction in the Acute Physiology and Chronic Health Evaluation (APACHE II) score was achieved by the end of infusion (p = .038) . A renal elimination mechanism for IL-1ra was suggested by the positive correlation between IL-1ra plasma clearance and estimated creatinine clearance (p = .001; r2 = .51) . Human recombinant IL-1ra was well tolerated . CONCLUSIONS: This initial evaluation suggests that human recombinant IL-1ra is safe and may provide a dose-related survival advantage to patients with sepsis syndrome . A larger, definitive clinical trial is needed to confirm these findings.

Ann Pharmacother, 1994 Jan, 28(1), 105 - 11
Assessment of cost-effective antibiotic therapy in the management of infections in cancer patients; Cimino MA et al.; OBJECTIVE: To describe the economic benefits of a quality improvement effort directed at optimizing clinical outcome . DESIGN: A before-after observational design was used to evaluate the cost-effectiveness of a consensus approach to antimicrobial therapy . SETTING: The evaluation was conducted at a cancer research hospital . PATIENTS: Oncology patients requiring parenteral antibiotic therapy were consecutively observed . MAIN OUTCOME MEASURES: Outcome (clinical and microbiologic response), safety, and cost of therapy were assessed during a baseline period and compared to a period during which the consensus approach was used . INTERVENTIONS: The influence of a designated individual, in this case a clinical pharmacist, responsible for promotion of the consensus approach was explored . RESULTS: The consensus approach in combination with the promotional efforts of the clinical pharmacist was associated with a 13 percent increase in overall clinical response and a reduction of pathogen persistence from 22 to 11 percent . No difference in the average number of adverse effects per patient was observed over the two observation periods . These findings were associated with an estimated $22,000/month cost savings . The consensus approach alone, without benefit of the clinical pharmacist, was not associated with improved therapeutic outcome or cost savings over the same observation periods . CONCLUSIONS: These data suggest that a consensus approach to antibiotic therapy can be cost-effective . An individual, such as a clinical pharmacist, may add significantly to quality improvement and cost-effective efforts in a hospital setting.

Oncology (Huntingt), 1994 Jan, 8(1), 33 - 7; discussion 38-40
Cervical and anal neoplasia and HPV infection in persons with HIV infection; Northfelt DW; Prolonged, severe immunodeficiency provides the necessary milieu for the emergence of anogenital neoplasia caused by human papillomaviruses . Cervical and anal neoplasia are likely to become more common manifestations of HIV disease as patients with profound immunodeficiency, who would have succumbed to opportunistic infections earlier in the epidemic, are now surviving for extended periods of time because of increasingly effective antiretroviral, prophylactic, and antimicrobial therapies . Cervical cancer in the setting of HIV infection appears to be a more aggressive disease, less likely to be successfully treated by standard therapies, and consequently associated with a poorer prognosis than in comparable non-HIV-infected women . Anecdotal observations suggest that anal cancer in HIV-infected persons may share these features . Strategies need to be developed for earlier detection and treatment of neoplasia and anogenital cancer in the setting of HIV-induced immunodeficiency.

Clin Orthop, 1994 Jan, (298), 229 - 39
An aggressive surgical approach to the management of chronic osteomyelitis; Eckardt JJ et al.; This is a review of 13 patients with chronic osteomyelitis treated at the author's institution using techniques similar to the management of giant cell tumors of bone . This included aggressive serial debridements and appropriate antibiotic coverage and subsequent bone-grafting or soft-tissue coverage procedures . The number of surgical procedures ranged from three to eight (average 4.2) and were performed every two to three days . Empiric antibiotics were started after cultures were taken at operation, and were changed to organism-specific therapy when culture results were available . Parenteral antibiotics were continued for a mean of five weeks (range, two to eight weeks) and seven of 13 patients received oral antibiotics for an additional two to six weeks after parenteral therapy . Bone grafting or muscle flaps or both were used in those patients with compromised structural integrity, or to fill created dead space and allow wound closure . In postoperative follow-up evaluation, none of the patients have had evidence for recurrent osteomyelitis (mean duration, 58 months; range, 27-89 months) . This technique of serial operations with proper antimicrobial therapy, followed by bone grafting and local muscle flaps when needed, has led to excellent end results in the treatment of chronic osteomyelitis.

Nephrol Dial Transplant, 1994, 9(5), 539 - 42
Treatment of fungal peritonitis complicating continuous ambulatory peritoneal dialysis with oral fluconazole: a series of 21 patients; Chan TM et al.; Twenty-one episodes of fungal peritonitis occurred over 35 months among 290 patients on CAPD, accounting for 6.3% of all peritonitis episodes . Patients with more frequent bacterial peritonitis were at higher risk of developing fungal peritonitis, and 28.6% of cases followed antimicrobial therapy . Candida species accounted for 85.7% of cases . Oral fluconazole was used as initial therapy in all patients, which was followed by catheter removal if peritonitis failed to improve . The cure rate with fluconazole therapy alone without catheter removal was 9.5% . Fluconazole plus catheter removal, the latter necessitated in 85.7% of cases, resulted in a cure rate of 66.7% . The remaining 3 (14.3%) patients responded to intravenous amphotericin given as salvage therapy . Disease-related mortality was 14.3% . Reinsertion of dialysis catheter was attempted in 15 patients and CAPD was successfully resumed in 13 (86.7%) . We conclude that oral fluconazole can be safely used as initial therapy in patients with fungal peritonitis complicating CAPD . Although catheter removal was necessary in the majority of patients, this sequential approach resulted in a relatively low prevalence of peritoneal adhesions and subsequent CAPD failure.

Klin Khir, 1994, (1-2), 4 - 7
{Use of multicomponent ointments on a hydrophilic base in the treatment of suppurative wounds}; Datsenko BM et al.; The results of experimental and clinical studies on the development of multicomponent ointments on a hydrophilic base for local treatment of wounds at phase I of the inflammatory process have been analyzed . A pronounced therapeutic effect of the use of the remedies suggested (levosin, levomecol, dioxycole, sulphamecole, iodmetroxide) resulting from simultaneous dehydrating, antimicrobial, necrolytic and anesthetic effect, 2-fold shortening of the period of wound treatment and improvement of the results of treatment of the patients with different types of purulent surgical infection were noted.

Int J Legal Med, 1994, 106(5), 237 - 43
Analysis of a new fluoroquinolone derivative (Q-35) in human scalp hair as an index of drug exposure and as a time marker in hair; Uematsu T et al.; Scalp hair samples were obtained every month for three months after administration from healthy male volunteers who participated in the phase I study of a new antimicrobial fluoroquinolone derivative (Q-35) . Hairs were cut into 1 cm long pieces successively from the scalp end . Corresponding pieces of 5 hair strands were dissolved in 1 M NaOH and assessed for Q-35 by HPLC . The drug was detectable in the hairs of all subjects taking either a single (400 mg, n = 6) or repeated oral doses of Q-35 (400 mg/day for 6.5 days, total 2600 mg, n = 6) . The hair portions containing the drug were shown in most subjects to move outwards along the hair shafts month by month in proportion to the hair growth rate of about 1 cm/month . Q-35 (600 mg/day) was also given to 6 healthy male volunteers for 6.5 days (total 3900 mg) and hair samples were obtained 1 and 3 months after administration . When Q-35 was analyzed along a single hair shaft, the drug was detectable only in 1-2 consecutive 1 cm long pieces, which were also shown to move outwards along the hair shaft with time . A detailed analysis revealed that the drug was contained only in 2-4 consecutive 2.5 mm long pieces of a single hair collected after 3 months, showing that there was no significant axial diffusion of the drug along the hair shaft with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Otolaryngol Suppl, 1994, 515, 18 - 21
Microorganisms and leukocytes in purulent sinusitis: a symbiotic relationship in metabolism; Westrin KM et al.; Since the exchange of gases, as well as metabolites, is greatly impeded in a paranasal sinus empyema, it is not unlikely that certain organic substances be retained and accumulated in purulent secretion . In this study, secretions aspirated from experimentally infected maxillary sinuses of 26 rabbits were analysed biochemically . Quantitatively, by far the most important acid accumulated in secretions was lactic acid . Lactate induces metabolic acidosis and exerts an inhibitory effect on mammalian defense mechanisms . Lactate may also be used as an energy source by certain microorganisms . In spite of its leukocytic origin lactic acid thus promotes the continuation of a bacterial infection . In addition, certain other organic acids of bacterial origin were found, which, in different ways, contribute to the impediment of antimicrobial defense functions.

Lik Sprava, 1994 Jan, (1), 61 - 3
{The effect of euphylline on the antimicrobial activity of antibiotics}; Biktimirov VV et al.; Antimicrobic properties of euphylline as well as its effects on antibacterial activity of penicillins, cephalosporins, and aminoglycosides were studied . It was established that euphylline differently affects antimicrobic activity of aforementioned drugs.

Antibiot Khimioter, 1994 Jan, 39(1), 33 - 7
{Ofloxacin in the comprehensive therapy of complicated forms of wound infection}; Blatun LA et al.; A 5-year experience with the use of ofloxacin in the complex treatment of complicated wound infections showed that the drug had a broad spectrum of antimicrobial activity, was not toxic and well tolerated by the patients . The side effects were extremely rare . The antimicrobial activity of ofloxacin after its clinical use for 5 years did not practically change . The drug clinical and bacteriological efficacy in different groups of the patients ranged within 85-91 and 74-80 per cent respectively depending on the process severity . The failure of the therapy was as a rule associated with an insufficient surgical treatment of the purulent foci . It was more frequent in the patients with arteriosclerotic and diabetic gangrene of the lower extremities when due to various reasons the initial surgical operations were not radical . The short treatment courses (for not more than 5-7 days) or an early use of the drug tablets instead of the intravenous injections resulted from an insufficient experience with ofloxacin during the first years of its use . Such an unjustified tactics did not provide stable elimination of the pathogen . Our experience with ofloxacin in the treatment of various groups of patients with wound infections demonstrated that it should be considered as a reserve drug for the treatment of cases with complicated wound infections accompanied by infections of the respiratory and uropoietic organs requiring a long-term antibacterial therapy in hospitals and outpatient departments.

J Clin Pediatr Dent, 1994 Winter, 18(2), 129 - 34
Antibiotics and dentistry: a brief review; Owens BM et al.; The history of dental disease has involved a variety of treatment modalities . This paper is a historical perspective of the evolution of modern antimicrobial compounds and their applications for dentistry . Many individuals have made tremendous contributions in this field, beginning more than a century ago . The two primary categories of antimicrobial agents are the naturally occurring antibacterial substances (antibiotics) and the compounds of synthetic origin . Agents of fungal origin (penicillins and cephalosporins), bacterial origin, and actinomycetes origin (aminoglycosides) comprise the former group while sulfanilamides, quinolones, and fluoroquinolones are included in the latter . The antibiotic groups of significance for dentistry are the penicillins, cephalosporins, and the aminoglycosides, including erythromycin . Due to its efficacy, low cost, and ease of administration penicillin has been the antibiotic of choice for many, if not most odontogenic infections . The agents of synthetic origin have some therapeutic value for dentistry . They are compromised by high cost, lack of effectiveness, or host toxicity.

Nephrologie, 1994, 15(2), 181 - 4
{The Carboclip, a new, atraumatic vascular access for hemodialysis}; Bonnaud P et al.; The Carboclip is a no-needle vascular access device made of an inverted Titanium body . The horizontal bar of 6 mm inner diameter is connected with artery and vein via a vascular graft . The vertical body houses an elastic plug in which is inserted a double canula diving in the blood stream for extracorporeal blood circulation (EBC) . The body is wrapped by a flange made of microporous biocarbon in which the subcutaneous fibroblast will growth, forming an antimicrobial barrier and fixing the port to the skin . We report our experience on 30 devices implanted in 30 sheep with 26 extracorporeal circulation simulating hemodialysis . The results demonstrate good tightness of the plug as well at rest as during EBC procedure, sufficient blood flow rate of about 400 ml/min, and benefits of the microporous carbon flange.

Compr Ther, 1994, 20(5), 300 - 5
The "peripneumonia" period in the older adult; Heuser MD et al.; CAP in the older adult is a complex multifactorial syndrome . Older adults are at increased risk for pneumonia and death associated with pneumonia . The prevalence and severity of risk factors for pneumonia increase with age . Although alterations in respiratory function occur with increased frequency in the elderly, immune senescence is probably the major predisposing factor contributing to the increased incidence, morbidity, and mortality of respiratory infection in the elderly . Yet, risk factors, once identified, may be amendable to interventions and health behavior modification to reduce the occurrence of pneumonia . Older patients discharged from the hospital after recovering from pneumonia are at increased risk for subsequent hospitalizations and death . Further studies are needed to explore the long-term consequences of pneumonia in the antimicrobial era on quality of life and physical and psychosocial functioning.

Compend Suppl, 1994, (18), S711 - 3; quiz S714-7
Chlorhexidine gluconate in periodontal treatment; Cohen DW et al.; Dr . Henry M . Goldman's contributions to periodontics are many, but none may be as significant as the work he did in the study of antimicrobial agents used to fight periodontal disease . This article presents a review of the literature on antimicrobial effectiveness of chlorhexidine gluconate and describes its role as a chemotherapeutic, antibacterial, antiplaque agent.

Compend Suppl, 1994, (18), S694 - 8; quiz S714-7
Periodontal complications of HIV infection; Greenspan JS; As the scope of the acquired immunodeficiency syndrome (AIDS) epidemic grows to include increasingly larger proportions of heterosexual adults and children, there has also been a change in the severity of human immunodeficiency virus (HIV)-related periodontal conditions at one San Francisco clinic . The cases of HIV-associated gingivitis, now called linear gingival erythema, HIV-associated periodontitis (or necrotizing ulcerative periodontitis), and necrotizing stomatitis have been less severe, despite an increase in overall HIV caseload . No clear basis for this trend has been established, but possible explanations include: biased population samples, increased immunosuppression as the disease matures, use of antimicrobial therapy, or a change in patient demographics . Several studies have failed to identify a single causative organism . This article presents a review of HIV-related periodontal complications and points out that the condition can be treated with local and systemic antibiotics and that dental professionals throughout the world can expect a tremendous increase over the next several years in HIV-infected patients with special clinical complications.

Prog Med Chem, 1994, 31, 265 - 95
Semi-synthetic derivatives of 16-membered macrolide antibiotics; Kirst HA; The fermentation-derived 16-membered and 14-membered macrolides have been equally productive sources of semi-synthetic derivatives which have significantly extended the utility of the macrolide class as important antibiotics . New derivatives, prepared by both chemical and biochemical methods, have exhibited a variety of improved features, such as an expanded antimicrobial spectrum, increased potency, greater efficacy, better oral bioavailability, extended chemical and metabolic stability, higher and more prolonged concentrations in tissues and fluids, lower and less frequent dosing, and/or diminished side-effects {302} . However, even more improvements are both achievable and necessary if problems such as resistance to existing antibiotics continue to rise {303, 304} . Newer semi-synthetic macrolides which satisfy these important needs should be anticipated as the contributions from new fields such as genetic engineering of macrolide-producing organisms and more powerful computational chemistry are combined with the more traditional disciplines of chemical synthesis, bioconversions, and screening fermentation broths.

Fundam Clin Pharmacol, 1994, 8(2), 173 - 7
Comparative study of erythromycin, troleandomycin and tylosin on the rabbit intestine; Kounenis G et al.; The macrolide antimicrobial agents, erythromycin, troleandomycin and tylosin were tested for their effect on isolated whole segments of the rabbit duodenum, jejunum, ileum and ascending colon, as well as on strips of the circular and longitudinal smooth muscle of the ascending colon . The 14-membered macrolides erythromycin and troleandomycin were found to possess a concentration-dependent contractile effect on the intestinal smooth muscle . The order of potency was: erythromycin > troleandomycin . The 16-membered macrolide tylosin was found to have a much weaker potency than erythromycin and troleandomycin . In addition, the circular smooth muscle of the ascending colon was found to be more sensitive to the compounds tested than the longitudinal smooth muscle.

Eur J Ophthalmol, 1994 Jan-Mar, 4(1), 6 - 12
Topical ciprofloxacin in the treatment of blepharitis and blepharoconjunctivitis; Bloom PA et al.; An international multicentre study assessed the clinical and antibacterial efficacy of a new topical ophthalmic formulation of the quinolone antimicrobial agent ciprofloxacin and compared it with that of tobramycin ophthalmic solution in patients with blepharitis and blepharoconjunctivitis . The study consisted of a randomised double-masked between-group evaluation of 464 patients, 230 of whom were treated with ciprofloxacin and 234 with tobramycin . There was qualitative and quantitative bacteriology, and clinical assessment of ocular symptoms and signs before and after a seven-day course of treatment . Bacteriological cultures demonstrated eradication or reduction of potentially pathogenic bacteria in 93.7% of eyes (ciprofloxacin) versus 88.9% of eyes (tobramycin), seven days after starting treatment . Clinically more than 80% of patients in both treatment groups were cured or improved after seven days . No statistically significant differences were observed between the two treatment groups . No serious side-effects were observed after use of either antimicrobial agent . Ciprofloxacin ophthalmic solution appears safe and effective . The spectrum of activity and clinical efficacy of this new formulation are discussed in comparison with currently used antimicrobial agents.

Eur J Cancer, 1994, 30A(4), 430 - 7
Factors associated with bacteraemia in febrile, granulocytopenic cancer patients . The International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC); Viscoli C et al.; The objective of this investigation was to determine factors predictive of bacteraemia at presentation in febrile, granulocytopenic cancer patients in order to estimate the probability of bacteraemia in each patient, and to compare factors associated with a diagnosis of gram-positive or gram-negative bacteraemia . Retrospective analysis of two sets of data (derivation and validation sets) randomly obtained from a large prospective study was conducted in a multicentre study of febrile, granulocytopenic cancer patients admitted for empiric antibacterial therapy . Within the derivation set, prognostic factors (clinical and laboratory data) likely to be associated with a generic diagnosis of bacteraemia and with a specific diagnosis of gram-positive or gram-negative bacteraemia were analysed by means of three backward, stepwise, logistic regression analyses . The predictive probability of bacteraemia was calculated using the logistic equation . The discriminating ability of the model in predicting bacteraemia was evaluated in the derivation and validation sets using receiver-operating characteristic curves . The predictive probability of gram-positive or gram-negative bacteraemia was not calculated . In the derivation set, 157 of 558 episodes (28%) were microbiologically documented bacteraemias . Predicting factors were antifungal prophylaxis, duration of granulocytopenia before fever, platelet count, highest fever, shock and presence and location of initial signs of infection . The variables institution, antibacterial prophylaxis and underlying disease showed borderline associations with bacteraemia . Shock was associated with gram-negative bacteraemia, while signs of infection at catheter site were predictive of gram-positive bacteraemia . Quinolone prophylaxis was negatively associated with gram-negative bacteraemia . When tested in the validation set, the model was poorly predictive, although a small subgroup of episodes (representing only 16% of the total sample size) with low risk of bacteraemia was identified . Factors predictive of bacteraemia can be identified, with discrimination between gram-positive and gram-negative aetiology . Further studies are warranted in order to improve the discriminant ability of the model.

Folia Microbiol (Praha), 1994, 39(3), 176 - 80
Quantitative relationships between structure and antimicrobial activity of new "soft" bisquaternary ammonium salts; Pavlikova-Moricka M et al.; New surface-active bisquaternary ammonium salts derived from bis-(2-dimethylaminoethyl) ester of glutaric acid are highly effective against representatives of Gram-positive, Gram-negative bacteria and yeasts . Relationships between structure, lipophilicity and antimicrobial effectiveness were demonstrated by quantitative structure-activity methodology . The non-linear dependence of biological activity on the structure as well as lipophilicity (expressed as critical micelle concentration-CMC) was shown using Kubinyi's bilinear model . The most effective compounds were those with the alkyl chain of 11-12 carbon atoms and with the CMC values around 0.7-1.0 mmol/L . These derivatives possessed higher antimicrobial activity particularly to Gram-negative bacteria.

Probl Tuberk, 1994, (4), 51 - 3
{Non-specific resistance of neutrophil granulocytes by cationic protein indices in the development of tuberculosis}; Sakharova II; The paper gives cytochemical findings of the lysosomal cationic system of neutrophilic granulocytes in the blood of 188 patients with various pulmonary tuberculoses . In infiltrative pulmonary tuberculosis which was first detected, the decrease in the activity of the lysosomal cationic system of neutrophils was adequate to the extent and severity of the process . The permanent increase in the antimicrobial potential of neutrophilic granulocytes in patients with fibrous and cavernous pulmonary tuberculosis is a defense response of the body, however with constantly progressive tuberculosis, there is inhibition of this defense system, which becomes an unfavourable sign . It can be assumed that the parameters of the activity of bactericidal systems in the neutrophilic granulocytes reflect, to a greater extent, both the activity of this system and the resistance of the whole body.

Arch Gynecol Obstet, 1994, 255(3), 153 - 5
Necrotizing fasciitis arising from episiotomy; Hausler G et al.; Necrotizing fasciitis is a fatal, rapidly progressive, often initially unrecognized condition . Mortality rates range from 30% to 76% . Prognosis depends on the delay of diagnosis, antimicrobial treatment and surgical excision of all necrotic tissue . A case of postpartum perineal necrotizing fasciitis arising from episiotomy is presented . Prompt recognition and aggressive therapy resulted in a favorable outcome despite significant morbidity.

Am J Nephrol, 1994, 14(3), 216 - 9
Verticillium peritonitis in a patient on peritoneal dialysis; Amici G et al.; We describe a case of peritonitis due to Verticillium spp . in a 33-year-old farmer on continuous ambulatory peritoneal dialysis (CAPD) for 3 months for end-stage renal failure due to chronic pyelonephritis . The etiologic agent was a hyaline hyphomycete which we report as a new human opportunistic pathogen . The fungus was isolated from the peritoneal fluid culture and from the tip of the catheter; identification was made on the basis of macroscopic and microscopic features . The patient had previously been admitted to our hospital for peritonitis caused by mixed enteric flora and treated for 8 days with intraperitoneal broad-spectrum antibiotic therapy . Five days after discharge he was readmitted for severe abdominal pain and cloudy drainage fluid . Two days of intraperitoneal broad-spectrum antimicrobial therapy produced no clinical improvement . Intravenous fluconazole and oral flucytosine were administered upon identifying the fungus . After another 2 days without improvement, peritoneal dialysis was discontinued and the catheter removed . Antimycotic therapy was continued for 4 days with complete resolution of the peritonitis . The patient chose to start hemodialysis and was discharged in good clinical condition.

Wien Klin Wochenschr, 1994, 106(17), 543 - 6
{Current therapy of Helicobacter pylori-induced chronic gastritis and/or peptic ulcer}; Hentschel E; Helicobacter pylori (H.p.) induced chronic gastritis cannot at present be considered as an absolute indication for eradication therapy of H.p . Clinical trials with antimicrobial compounds, mainly bismuth, have not convincingly demonstrated appreciable symptomatic benefit for patients with H.p.-positive gastritis and non-ulcer dyspepsia . However, new results indicate that possibly a longer follow-up period may be necessary to prove a symptomatic improvement after H.p . eradication in patients with chronic gastritis . In contrast, eradication of H.p . reduces the relapse rates of recurrent non-iatrogenic peptic ulcer to virtually zero . Antimicrobial treatment of H.p . infection is, therefore, clearly indicated in chronic duodenal and gastric ulcers . In the case of success, drug maintenance therapy or operation becomes superfluous . The combination of amoxicillin plus metronidazole with ranitidine or of omeprazole with amoxicillin or clarithromycin results in eradication rates of about 85% . Triple therapy with bismuth, metronidazole, and amoxicillin or tetracycline is successful in about 90% of patients but the incidence of side effects is higher.

Folia Microbiol (Praha), 1994, 39(2), 152 - 4
Antimicrobial effects of new 1-(1,2,4-triazol-1-yl)-acetanilides; Jantova S et al.; Fourteen synthetically prepared 1-(1,2,4-triazol-1-yl)acetanilides were tested for antimicrobial effect . None of the prepared derivatives influenced the B . subtilis, P . fluorescens nor the tested yeasts . Only the derivatives with substituents in positions para or ortho and para were biologically effective . The widest antimicrobial spectrum was manifested by the pentachloro derivative, which was effective with G+ and G- bacteria and with filamentous fungi.

Probl Tuberk, 1994, (3), 59 - 62
{Enhancement of the activity of antitubercular agents with other antimicrobial agents}; Vinogradova TI; The experimental studies have provided strong evidence that the efficacy of etiotropic therapy for tuberculosis can be enhanced by applying a number of antimicrobial agents having different mechanism of action, which belong to cephalosporins, macrolides, aminoglycosides, fluoroquinolones . The basis of the mechanism responsible for potentiation of activity of essential tuberculostatic drugs for potentiation of activity of essential tuberculostatic drugs is enhanced inhibition of the viability of a microbacterial population, prevented development of drug resistance in tuberculosis mycobacteria, and increased function of macrophages.

Mycoses, 1994 Jan-Feb, 37(1-2), 35 - 8
Fluconazole-resistant oral candidosis in a repeatedly treated female AIDS patient; Thomas-Greber E et al.; A 29-year-old female suffering from full-blown AIDS received fluconazole 400 mg day-1 for a long period for treatment of oral candidosis, pseudomembranous type . She had previously received this drug repeatedly for the same reason, yet manifest disease persisted . She was therefore put on parenteral amphotericin B, which led to clinical, but not mycological, cure in the short term . IC30 testing revealed a minimum inhibitory concentration (MIC) > 128 micrograms ml-1 for fluconazole . The isolate, however, was susceptible in vitro to ketoconazole, itraconazole and amphotericin B . The same antimicrobial susceptibility pattern was found with a second isolate obtained later . Resistance to fluconazole might become a major problem in HIV-infected patients receiving this drug for long periods.

Med Trop (Mars), 1994, 54(2), 149 - 51
{Retropharyngeal abscess . 6 case reports}; Ouoba K et al.; From 1983 to 1991, 6 cases of retropharyngeal abscess were treated at the University Hospital Center of Dakar . A retrospective review of these cases showed that most occurred in children between the ages of 3 months and 3 years . All patients were examined late, i.e . with a delay of more than one week between the onset of symptoms and consultation of a specialist . The clinical signs were dysphagia, dyspnea, and, in all but one case, fever . In 5 patients, diagnosis was based on the observation of a mass in the middle section of the posterior wall of the pharynx that led to peroral incision and drainage without general anesthesia . In the remaining patient, whose abscess involved the lower part of the wall, endoscopy was necessary to allow diagnosis and incision under general anesthesia after tracheotomy . In all cases, complete healing was obtained after 10-day single-agent antimicrobial therapy . Practitioners in tropical areas should bear in mind that retropharyngeal abscesses are not uncommon in these regions and that they can cause serious complications (rupture and mediastinal extension).

J Formos Med Assoc, 1994 Jan, 93(1), 35 - 9
Quantitative measurement of drug susceptibility of Mycobacterium tuberculosis for monitoring chemotherapy response; Chen CH et al.; Changes in the degree of drug susceptibility of the bacterial population in tuberculosis patients during chemotherapy can be monitored by testing Mycobacterium tuberculosis isolates against various concentrations of drugs in 7H12 broth to determine radiometrically the minimal inhibitory concentration (MIC) . The MICs were determined for multiple cultures isolated from 13 patients, of whom nine responded to chemotherapy within a few months, and four failed to respond at all . No changes in MICs were observed with the isolates obtained from the patients with a favorable response to chemotherapy . Determination of the MICs indicated that the failure in two cases out of four was associated with a steady increase in the degree of resistance of the patients' bacterial population . In two other failure cases, lack of change in the MIC values for multiple cultures suggests that the failure was associated with factors other than drug resistance . During the period of chemotherapy, quantitation of the degree of drug susceptibility in terms of broth-determined MICs may help to identify promptly those patients whose bacterial population is becoming resistant to the administered antimicrobial agents . For those patients who do not respond to chemotherapy, lack of change in the degree of resistance of their bacterial population may alert the physician to attempt to identify causes other than drug resistance for the chemotherapy failure.

Med Trop (Mars), 1994, 54(3), 242 - 6
{Typhoid perforations: experiences in a surgical setting in Cameroon . Apropos of 49 cases}; Yao JG et al.; Over a period of 3 years, 49 typhoid perforations of the small intestine were treated at Yaounde Central Hospital . These 34 men and 15 women with a mean age of 29.6 years presented sthenic peritonitis in 20 cases and more difficult to diagnose asthenic peritonitis in 29 cases . The perforation was always located at the end of the ileum and was single in 40 cases, double in 6 cases and triple in 3 cases . Surgical management in association with intensive care and multiple agent antimicrobial therapy consisted in sleeve resection in 29 cases, resections with an exteriorized anastomosis in 15 cases, and ileocolonic intubation in 5 cases . The postoperative complications were suppuration of the wall (n = 4), intestinal fistula (n = 3), evisceration, and residual abscess . There were 9 deaths (18.4%) including 4 after sleeve resection and 5 after resection with an exteriorized anastomosis . On the basis of this experience, the authors describe the diagnostic difficulties posed by typhoid perforations, discuss surgical techniques proposed in the literature, and emphasize the value of sleeve resection.

Med Tr Prom Ekol, 1994, (7), 29 - 32
{Use of insoles made of antimicrobial materials as prophylactic means in foot mycoses}; Sedov AV et al.; Stationary dermatologic examination covered 32 sufferers from epidermophytosis of soles, who used 3 types of antimicrobial insoles chosen through laboratory investigations . Clinical trials proved that antimicrobial insoles, if applied during 2 weeks, result in considerably decreased occurrence of causal fungus in the patients' surface skin scarring . The results proved fungicidal and bactericidal activity of insoles including furagin, nitrofurilacroleine, polyhexamethylene guanidine, so such insoles could be recommended as prophylactic measure for mycoses of soles.

Pneumonol Alergol Pol, 1994, 62(9-10), 530 - 2
{Moraxella catarrhalis as an important etiologic factor in infection of the lower bronchial tree}; Nowak-Sadzikowska J et al.; Moraxella catarrhalis in responsible for a considerable number of bronchopulmonary infections in adults, as well as otitis media and sinusitis in children . Many strains of Moraxella catarrhalis produce beta-lactamase and are resistant to many beta-lactam antibiotics . When Moraxella catarrhalis in considered to be a causative organism, the choice for an empiric antimicrobial therapy should be beta-lactamase-resistant antibiotics.

Biotherapy, 1994, 7(3-4), 161 - 7
Interleukin-1 and related pro-inflammatory cytokines in the treatment of bacterial infections in neutropenic and non-neutropenic animals; van der Meer JW et al.; Bacterial infections in the immunocompromized host cause considerable mortality, and even the recently developed antimicrobial strategies often fail to cure these infections, especially in granulocytopenic patients . Cytokines and hematopoietic growth factors have been shown to stimulate host defense mechanisms in vitro and in vivo . We discuss the possible role of the pro-inflammatory cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 as modulators of host resistance to bacterial infections . Interleukin-1 has been shown effective in various animal models of potentially lethal bacterial infection, even during severe granulocytopenia . The protective mechanism of interleukin-1 may be mediated via downregulation of cytokine receptors and cytokine production, and via induction of acute phase proteins . Moreover, in subacute and chronic infections interleukin-1 interferes with microbial outgrowth, via mechanisms that have only been partially elucidated.

Eur J Clin Pharmacol, 1994, 47(2), 195 - 202
Using ofloxacin as a time marker in hair analysis for monitoring the dosage history of haloperidol; Nakano M et al.; Hair samples were obtained 1-5 months after ingestion of the antimicrobial ofloxacin, which had been given for 1 or 3 days at the commencement of haloperidol administration, or when its dosage was reduced . The axial distribution of ofloxacin, haloperidol and its active metabolite, reduced haloperidol, was analysed in segments from single strands of hair . Ofloxacin was detected where the content of haloperidol and reduced haloperidol along the hair shaft showed a sharp change, corresponding to the change in dose . When we matched the time scale of the dosage history to the growth rate, which was estimated using ofloxacin as the time marker, the distribution of the haloperidol and reduced haloperidol precisely coincided with the rise and fall in the dose of haloperidol . These findings demonstrate that ofloxacin can serve as a time marker when drug distribution along the hair shaft is used to obtain the drug exposure history of an individual.

Br J Neurosurg, 1994, 8(5), 545 - 50
Actinomycotic brain abscess successfully treated by burr hole aspiration and short course antimicrobial therapy; Jamjoom AB et al.; Three cases of brain abscess caused by Actinomyces israelii are reported which were successfully treated by burr hole aspiration and a short course of antibiotics (3-4 weeks) . The clinical response of the patients, as well as the serial serum C-reactive protein levels and CT findings were used as a guideline for stopping antimicrobial therapy relatively early.

Wien Med Wochenschr, 1994, 144(10-11), 273 - 6
{Local therapy of ulcus cruris}; Aubock J; The primary step of local ulcer therapy consists in debridement . Cleaning the ulcers from necrotic tissue can be achieved by surgical, mechanical, osmotic, autolytic and enzymatic means . The introduction of (semi-)occlusive wound dressings for moist wound healing has significantly improved ulcer treatment, since critical steps of wound healing, such as fibroblast proliferation, angiogenesis and epithelialisation are markedly accelerated . In contrast, topical antimicrobial therapy and traditional local treatment with "wound ointments" are of diminishing value because of frequent side effects such as inhibition of granulation tissue or allergic sensitization.

Caries Res, 1994, 28(6), 429 - 34
Fluoride inhibits the antimicrobial peroxidase systems in human whole saliva; Hannuksela S et al.; Fluoride (F-) ions at concentrations present in vivo at the plaque/enamel interface (0.05-10 mM) inhibited the activities of lactoperoxidase (LP), myeloperoxidase (MP) and total salivary peroxidase (TSP) in a pH- and dose-dependent way . The inhibition was observed only at pH < or = 6.5 and with F- concentrations > or = 0.1 mM . At pH 5.5 LP activity was inhibited by 85% and MP by 34% with 10 mM F- . TSP activity was also inhibited only at low pH (5.5) by approximately 25% . Furthermore, the generation of the actual antimicrobial agent in vivo, hypothiocyanite (HOSCN/OSCN-), of the oral peroxidase systems was inhibited by F-, again at low pH (5.0-5.5) both in buffer (by 45%) and in saliva (by 15%) . This inhibition was observed only with the highest F- concentrations studied (5-10 mM) . Fluoridated toothpaste (with 0.10 or 0.14% F) mixed with saliva did not inhibit TSP or HOSCN/OSCN- generation . This may have been due to the 'buffering' effect of toothpaste which did not allow salivary pH to drop below 5.9 . We conclude that the F- ions in acidic fluoride products, e.g . in gels or varnishes (but not in toothpastes), may have the potential to locally inhibit the generation of a nonimmune host defense factor, HOSCN/OSCN/SCN-, produced by oral peroxidase systems . The possible clinical significance of this finding remains to be shown.

Miner Electrolyte Metab, 1994, 20(4), 221 - 31
Renal tubular transport and nephrotoxicity of beta lactam antibiotics: structure-activity relationships; Tune BM; Several of the cephalosporin and carbapenem antibiotics produce acute renal failure when given in large single doses . Antibiotic concentrations in the tubular cell, determined by the net effects of contraluminal secretory transport and subsequent movement across the luminal membrane, make the proximal tubule the sole target of injury, and are important determinants of the nephrotoxic potentials of different beta-lactams in different animal species . At least three molecular mechanisms of injury have been shown with cephaloridine, the most widely studied nephrotoxic beta-lactam: (1) lipid peroxidation, (2) competitive inhibition of mitochondrial carnitine (zwitterionic) transport and fatty acid oxidation, and (3) acylation and inactivation of tubular cell proteins, most thoroughly evaluated with mitochondrial anionic substrate transporters . The first two of these injuries are dependent upon one or both of cephaloridine's side group substituents, which are not present on the other nephrotoxic cephalosporins or carbapenems . It is not surprising, therefore, that only toxicity to mitochondrial anionic substrate carriers has been found in studies of the other beta-lactams . However, the several effects of cephaloridine on the tubular cell indicate a potential for different mechanisms of attack on different molecular targets . Continuing studies of the effects of existing and newly developed beta-lactams are likely to identify further nephrotoxic mechanisms of this complex and rapidly growing group of antimicrobials.

Infection, 1994, 22 Suppl 3, S176 - 81
Antimicrobial drug utilisation in hospitals in Italy and other European countries; Guglielmo L et al.; Antibiotic prescribing patterns in hospitals are analysed in this review of three drug utilisation studies conducted in six European countries, with special emphasis to the third-generation cephalosporins . A great variability in the use of antimicrobial drugs is evident, both between countries and between hospitals in the same country . This variability is found also between patients with the same infectious disease . The possible reasons for these differences are discussed and a strategy to modify the hospital drugs prescribing is suggested.

Annu Rev Microbiol, 1994, 48, 585 - 617
MSCRAMM-mediated adherence of microorganisms to host tissues; Patti JM et al.; Microbial adhesion to host tissue is the initial critical event in the pathogenesis of most infections and, as such, is an attractive target for the development of new antimicrobial therapeutics . Specific microbial components (adhesins) mediate adherence to host tissues by participating in amazingly sophisticated interactions with host molecules . This review focuses on a class of cell surface adhesins that specifically interact with extracellular matrix components and which we have designated MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) . MSCRAMMs recognizing fibronectin-, fibrinogen-, collagen-, and heparin-related polysaccharides are discussed in terms of structural organization, ligand-binding structures, importance in host tissue colonization and invasion, and role as virulence factors.

Klin Khir, 1994, (6), 48 - 50
{An agent imparting antimicrobial properties to woven materials}; Rudichenko VF et al.; The proposed agent for the woven materials impregnation gives them antibacterial properties concerning gram-negative and gram-positive microflora, and have also the fungicidal activity . It high effectiveness testifies the vast resources of an agent in the treatment and prophylaxis of surgical pyo-inflammatory infection.

Ann Fr Anesth Reanim, 1994, 13(2), 177 - 81
{Value of the cytology of bronchoalveolar lavage in the early diagnosis of nosocomial lung infections in patients with thoracic injuries}; Allaouchiche B et al.; Mechanically ventilated patients, especially those with thorax trauma, suffer commonly from nosocomial pneumonia . In these patients, conventional diagnostic criteria for bacterial pneumonia may not be completely reliable, as an accurate interpretation of the chest radiograph is too difficult . The invasive means for the diagnosis of pneumonia (protected specimen brush, bronchoalveolar lavage), require 24-48 hours to obtain the results of cultures . Therefore no information is available to guide the initial choice of antimicrobial therapy . For some authors, the quantification of intracellular bacteria, present in cytocentrifuged preparations made from lavage fluid, may provide rapid identification of patients with pneumonia . We evaluated the benefit of this type of analysis in thorax trauma patients . In 36 patients, 48 samples were taken . With a threshold value of 10% of cells containing intracellular organisms, microscopic examination had a sensitivity and a specificity of 83% . We conclude that this technique may be useful for the early diagnosis of nosocomial pneumonia in ventilated thorax trauma patients.

Retina, 1994, 14(4), 297 - 304
Treatment of endophthalmitis after cataract extraction; Doft BH et al.; BACKGROUND: A series of 34 patients was prospectively treated for postoperative endophthalmitis according to a specific protocol . The data are from the pilot study performed before initiation of the Endophthalmitis Vitrectomy Study (EVS) . METHODS: Patients with bacterial endophthalmitis that developed within 6 weeks of cataract extraction received intravitreal amikacin and vancomycin, subconjunctival and topical antimicrobials and corticosteroids, and systemic corticosteroids . All patients had diagnostic samples removed from the aqueous and vitreous, with randomized assignment to immediate vitrectomy versus vitreous tap and treatment with or without intravenous antibiotics . Outcome was evaluated 3 and 9 months after treatment . RESULTS: At the 9-month visit, visual acuity was 20/50 or better in 49% of all eyes, 20/200 or better in 79%, and 5/200 or better in 91% . Media clarity was such that a "20/40 or better view" of the retina was present in 71% of patients at 3 months and in 97% at 9 months . CONCLUSION: This is one of the largest series of patients with postoperative endophthalmitis treated and evaluated under a prospective protocol and without selection bias . Each of the options used in this study to treat postoperative endophthalmitis may result in good visual results.

Klin Khir, 1994, (5), 52 - 4
{The use of ozone for treating suppurative wounds}; Beligotskii NN et al.; Pathogenetic substantiation of the use of ozone for the treatment of purulent infection in surgery is given . A technique for the use of the method and its advantages as compared to antimicrobial remedies is described . A comparative assessment of the effectiveness of the suggested and existing methods was carried out.

Schweiz Arch Tierheilkd, 1994, 136(10), 329 - 34
{Pharmacokinetics of baytril (enrofloxacin) in dogs}; Kung K et al.; Baytril with the active ingredient enrofloxacin was given to four dogs in a single intravenous and oral dose of 5 mg/kg body weight . Measured plasma concentrations were different depending on the method of analysis used . Using high performance liquid chromatography quantitative determination of both enrofloxacin and its main metabolite ciprofloxacin is possible whereas antimicrobially active substance is measured by bioassay . Ciprofloxacin occurred early in the concentration-time curves after intravenous and oral administration of the parent drug enrofloxacin with cmax 0.2 and 0.3 microgram/ml, respectively, at tmax 2 and 4 h, respectively . Areas under the curve (AUC) calculated from concentration-time-curves with bioassay data are overestimated, because ciprofloxacin may be more active than enrofloxacin against E . coli 14 (ICB 4004) used in this test . Thus, pharmacokinetic parameters which are derived from AUC-values are overestimated, too . Oral bioavailability calculated with bioassay results was more than 100% whereas availability of enrofloxacin was only 53% . Clearance was 10.3 ml/min.kg (antimicrobially active substance) and 27.1 ml/min.kg (enrofloxacin) . Elimination half life was 3.7 and 2.4 h, respectively.

Klin Khir, 1994, (4), 22 - 5
{Prevention of peritonitis after surgery of the stomach and large intestine}; Datsenko BM et al.; We have used the combined preparation of foamy aerosol Gyposol-A and nitasol for the prophylaxis of postoperative peritonitis, originated due to gastrojejunal and colo-colonic anastomoses insufficiency . The introduction of preparation via the colonic tube ensures the physical hermetic control of anastomosis and allows to optimize the reparative processes by means of local antimicrobial, antiinflammatory, and stimulant action . Method was used in 76 patients . The frequency of postoperative peritonitis occurrence decreased from 20 to 2.3%.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S96 - 9
{Prophylactic antibiotic therapy in ocular surgery}; Bron A; Prophylactic antibiotics have been used by ophthalmic surgeons routinely before and after surgery . However, the optimal type of antibiotics and route of administration have not yet been clearly established . In this article, ocular surgery patterns, bacteriology and pharmacokinetics of antibiotics within the eye are reviewed, to try to provide rationale for antimicrobial prophylaxis.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S88 - 92
{Antibiotic prophylaxis in vascular surgery}; Kitzis M; Vascular surgery includes various surgical procedures and sites . Infectious risk is low but with a high functional risk and a high mortality rate . Infection risk factors are numerous . Among them the incision in the Scarpa's triangle is at the first place . Antimicrobial prophylaxis in vascular surgery has shown its efficacy whatever the agent . The second generation cephalosporins are the most logical, with a duration of administration of less than 24 hours . In case of re-operation glycopeptides have shown their efficacy.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S34 - 44
{Pharmacokinetic criteria of the choice of antibiotic for antibiotic prophylaxis in surgery}; Garraffo R et al.; The prevention of surgical infections with perioperative prophylactic antibiotics is experimentally and clinically well founded in both principle and practice . The evaluation of the role of antimicrobial agents in the success of failure of infection prophylaxis in surgery involves a discussion of both the pharmacokinetic and the pharmacodynamic properties of particular agents . A main concern in surgical prophylaxis is the relation between the respective time course of antibiotic concentrations in serum and in the tissue (wound) . Several problems arise in both the measurement and the interpretation of drug concentrations in tissues and the results of this approach are still controversial . However, the knowledge of the numerous factors influencing the penetration into a tissue and the characteristics of the relative distribution of the antibiotic between the compartments inside the tissue, i.e . the vascular, interstitial and intracellular spaces, could allow a valuable approach to this problem . The concentrations of free drugs in serum are valuable predictors of the time course of unbound drug in interstitial fluid, where the bacteria are generally located . An increase in protein binding does not reduce the area under the curve (AUC) of free drug for beta lactam agents eliminated predominantly by glomerular filtration, but prolongs their elimination half life . Timing and route of administration are also important factors to consider in relation with the pharmacokinetic profile of the drug . Pharmacodynamic studies of persistent growth suppression and bactericidal activity predict that the period during which the free drug concentration exceeds the MIC is an important parameter of the efficacy of beta lactam antibiotics . In the opposite, the Cmax and/or the AUC are the major parameters of the efficacy of aminoglycosides and quinolones against Gram negative bacteria . Thus, the goal of prophylaxis with beta lactams could be to provide levels of free drug above the MIC for the whole surgical period, while the obtention of a high Cmax with a one-day therapy should be required for aminoglycosides . Further clinical trials are warranted to assess this approach.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S25 - 33
{Microbiologic criteria of the choice of antibiotic for antibiotic prophylaxis in surgery}; Drugeon HB; The choice of an antibiotic for antimicrobial prophylaxis is based on microbiological, pharmacokinetic, chemical and pharmacodynamic parameters . The knowledge of the bacterial flora allows the identification of bacteria which could be responsible for postsurgical infections . These floras are complex and their equilibrium can be modified by various factors, such as hospitalization, co-existing disease, medico-surgical procedure, administration of antibiotics, which cause the selection of the so-called hospital-bacteria feared by therapists . The infection will develop according to the quantity of bacteria that have been introduced and to their virulence, which is often altered by local factors, especially the biomaterials . The knowledge of pharmacodynamic parameters such as bactericidal activity, postantibiotic effect, activity on virulence factors (bacterial adhesion), allows the refinement of the choice of the antibiotic and the optimization of its posology.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S19 - 24
{Economic aspects of surgical antibiotic prophylaxis}; Stahl JP et al.; The cost of an antibiotic is easily evaluated in the case of antimicrobial prophylaxis . The other expenses, either direct or indirect costs, are much more difficult to assess . Studies evaluating the economical impact of the prophylactic antibiotics are rather rare . Antibiotic prescription for prophylaxis is evaluated to represent about 20 to 30% of the total antibiotic administration in French hospitals . The most significant studies evaluate the cost/benefit ratio and demonstrate the advantage of prophylaxis in orthopaedic, vascular and gynaecologic surgery.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S173 - 8
{The role of new molecules in surgical antibiotic prophylaxis}; Raoult D et al.; The preoperative administration of a new antibiotic for antimicrobial prophylaxis is questionable because of the methodological difficulties to demonstrate its efficiency and benefits in decreasing the postoperative infectious complications . As their rate is very low, especially in clean surgery, the number of patients to be included in a comparative trial is very high . Most studies assessed only small groups and therefore any extrapolation for clinical practice is of limited value . Because of their therapeutic efficiency the fluoroquinolones are often recommended for antimicrobial prophylaxis . However, the rapid occurrence of resistances, directly related to their prescription should invite the prescribers to be cautions . They should be contra-indicated as long as an alternative of similar efficiency is existing, in case of bacteraemia, when an administration of more than 48 hours in required or when the intra-hospital resistance rate exceeds 10 p . 100.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S145 - 53
{Antibiotic prophylaxis in colorectal surgery}; Dellamonica P et al.; In elective colorectal surgery, the benefit of preoperative antibiotic prophylaxis is well established, with a reduction in wound infection rate to less than 10% . The antimicrobial agent used has to be active against aerobic and anaerobic pathogens such as Escheria coli and Bacteriodes fragilis . The efficacy of three schemes of administration: oral and/or parenteral prophylaxis associated with a mechanical preparation, has been demonstrated . Oral antibiotic administration is current practice in USA; the most widely used oral regimen is the combination of erythromycin and neomycin given the day before surgery . Parenteral prophylaxis with a cephalosporin active against Bacteriodes fragilis such as cefoxitin and cefotetan, is preferred in Europe . The issue of whether a systemic prophylaxis should be added to the oral regimen or not has not yet been resolved . However it seems that the association should be proposed in various situations: patients with a high risk factors score (rectal resection and operations lasting more than three hours), patients with incomplete mechanical preparation, delay of the onset of surgery after the last oral dose.

Ann Fr Anesth Reanim, 1994, 13(5 Suppl), S128 - 34
{Antibiotic prophylaxis in cesarean section and voluntary termination in pregnancy}; Fernandez H; Infection is the main complication after voluntary termination of pregnancy through vacuum aspiration, with an infection rate of 3.6% in the subsequent three weeks . This rate is comparable to that observed in the so-called clean surgical procedures . However the consequences on fertility remain unknown . Studies using systematic antibiotic administration in all vacuum aspirations (voluntary termination of pregnancy and spontaneous abortion) demonstrated the value of such a preventive measure . Factors of risk are difficult to identify and systematic bacteriological specimen collection in all patients undergoing a termination of pregnancy is quite impossible to do . Therefore, the best strategy consists in the oral administration of 200 mg of doxycycline before the aspiration and 200 mg 12 hours later . The incidence of operative-site infection and endometritis after Caesarean section without perioperative antimicrobial prophylaxis varies from 5 to 85% . A variety of risk factors have been identified such as low social category, rupture of membranes, the number of vaginal examinations, labour, and emergency sections . Most clinical trials have shown no significant difference in the efficacy of various antibiotic regimens . However, prophylactic antibiotics decrease significantly the rate of infections . We recommend one or three doses of intravenous prophylactic antibiotic, after clamping and section of the umbilical cord in high risk patients . Cephalosporin of 1st or 2nd generation or ampicillin associated with an inhibitor of beta-lactamases are recommended.

Ciba Found Symp, 1994, 186, 91 - 101; discussion 101-6
Gene-encoded antimicrobial peptides from plants; Cammue BP et al.; On the basis of an extensive screening of seeds from various plant species, we have isolated and characterized several different antimicrobial peptides . They were all typified by having a broad antifungal activity spectrum, a relatively low molecular weight (3-14 kDa), a high cysteine content and a high isoelectric point (pI > 10) . With respect to their amino acid sequence, these peptides can be classified into six structural classes . Synergistic enhancement (up to 73-fold) of antimicrobial activity was demonstrated in some combinations of peptides belonging to different classes . cDNA clones corresponding to different antifungal peptides were isolated and used to transform tobacco plants . Extracts of these transgenic plants showed higher (up to 16-fold) antifungal activity than untransformed control plants . Such antimicrobial peptides may find applications in molecular breeding of plants with increased disease resistance.

Ciba Found Symp, 1994, 186, 77 - 85; discussion 85-90
Antimicrobial peptides from amphibian skin: an overview; Kreil G; Over the past three decades, numerous peptides have been isolated from amphibian skin secretions . Many of these peptides were shown to be homologous to hormones and neurotransmitters of mammals . In recent years it has been shown that these secretions also contain a multitude of antimicrobial peptides . Most of these peptides are positively charged and have a propensity for forming an amphipathic helix . Other types of peptides have been detected as well, including one group which contain D-allo-isoleucine in their sequences . This work has mainly been done with three species from different families, Xenopus laevis, Bombina variegata and Rana esculenta . Each of these frogs produces distinct sets of peptides which are not related to those of other species . It can therefore be expected that many additional peptides with antimicrobial activity are present in amphibian species from other families.

Ciba Found Symp, 1994, 186, 62 - 71; discussion 71-6
Biosynthesis of defensins and other antimicrobial peptides; Ganz T; Defensins are small (about 30 amino acid residues) cationic antimicrobial peptides with a conserved framework of six disulphide-linked cysteines . Human defensin HNP-1 and the closely related HNP-3 are amphiphilic dimers that act in part by permeabilizing cell membranes . Defensin mRNAs, abundant in neutrophilic promyelocytes, certain non-human macrophages and Paneth cells, encode 94-100 amino acid prepropeptides . PreproHNP-1 is post-translationally processed to inactive proHNP-1 then to mature HNP-1 stored in granules . Bactenecin Bac-5 and perhaps other related neutrophil peptides are also synthesized as prepropeptides but are stored in granules as inactive propeptides . Their conserved cathelin-like propiece inhibits the cysteine protease, cathepsin L, and is removed only during granule release . Charge neutralization of mature peptide by the propiece is seen in both probactenecins and prodefensins . In contrast the propiece of cecropins is very short and proceropins are microbicidal . The pathways that convert myeloid preprodefensins to defensins are specific to myeloid cells but the signal for targeting to granules also functions in non-myeloid granulated cells . The truncation of the anionic propiece by deletion mutagenesis dramatically reduces defensin synthesis, suggesting that the propiece may assist in peptide stabilization, folding or subcellular transport . Despite some similarities in the mechanism of action of the various families of antimicrobial peptides, their precursors differ greatly, presumably owing to differing functions of the propieces.

Ciba Found Symp, 1994, 186, 5 - 20; discussion 20-6
Design and synthesis of antimicrobial peptides; Merrifield RB et al.; The cecropins are a group of potent antimicrobial peptides, initially discovered in insects but later found in other animals including mammals . Synthetic peptide chemistry has played an important role in establishing their primary sequences, as well as the steps in the processing of the biosynthetic preprocecropins . Solid-phase peptide synthesis has been the method of choice . Synthetic chimeric peptides have led to more active products and a better understanding of their mode of action . The structural requirements for high activity include a basic amphipathic N-terminus, a short central flexible sequence and a hydrophobic helical C-terminus . Cecropin-melittin hybrids as small as 15 residues are highly active . In planar lipid bilayers the cecropins form pores which pass ions and carry a current under a voltage gradient . Synthetic D-enantiomers of several antibacterial peptides carry the same current as the natural all-L-peptides and are equally active against several test bacteria . Therefore, the activity is not dependent on chiral interactions between the peptides and the lipid bilayers or the bacterial membranes . Recent examination of retro and retroenantio peptides has further defined the limits of the structural requirements of these peptides . Some of the hybrid peptides are active against Plasmodium falciparum and Mycobacterium smegmatis.

Ciba Found Symp, 1994, 186, 250 - 60; discussion 261-9
Antimicrobial peptides as agents of mucosal immunity; Bevins CL; Mucosal surfaces are continually exposed to a wide range of potentially pathogenic organisms, yet the incidence of infectious disease resulting from these encounters is relatively low . This suggests the presence of highly effective defence mechanisms in these tissues . Antimicrobial peptides have recently been discovered in mucosal tissues and may play a significant role in host defence . Several mucosal peptides (andropin, magainin, tracheal antimicrobial peptide, enteric defensins and PR-39) all fulfil minimal criteria for a role in mucosal host defence, including potent in vitro antimicrobial activity and accumulation at the mucosal surface . Most of these mucosal peptides are encoded by members of large gene families that contain members found in other biological contexts more classically associated with antimicrobial defence . The abundance, activity and evolutionary history of several epithelial peptides suggest that antimicrobial peptides play a key role in host defence at mucosal surfaces.

Ciba Found Symp, 1994, 186, 237 - 47; discussion 247-9
Antimicrobial proteins with homology to serine proteases; Gabay JE; The azurophil granule, a specialized lysosome of human neutrophils, contains a family of antimicrobial proteins with structural homology to serine proteases, the serprocidins . Three members of this family are serine proteases (cathepsin G, elastase and proteinase-3) and one is a proteolytically inactive homologue (azurocidin) . They are synthesized as preproproteins with a characteristic leader peptide and a propiece, both of which are removed by processing enzymes to yield the mature protein . The functional genes for three serprocidins (elastase, proteinase-3 and azurocidin) are grouped in a single genetic locus on chromosome 19 and are coordinately expressed and regulated during haemopoietic differentiation . Multiple and sometimes overlapping biological functions are a feature of this family, yet they all seem to pertain to host immunity . The structural requirements for the function of one member of this group (azurocidin), particularly its antibiotic function, are under investigation.

Ciba Found Symp, 1994, 186, 197 - 216; discussion 216-23
Potential therapeutic applications of magainins and other antimicrobial agents of animal origin; Jacob L et al.; Magainins are a family of linear, amphipathic, cationic antimicrobial peptides, 21 to 27 residues in length, found in the skin of Xenopus laevis . They kill microbial targets through disruption of membrane permeability . They exhibit selectivity, on the basis of their affinity for membranes which contain accessible acidic phospholipids, a property characterizing the cytoplasmic membranes of many species of bacteria . Magainins are broad-spectrum antimicrobial agents exhibiting cidal activity against Gram-negative and Gram-positive bacteria, fungi and protozoa . In addition these peptides lyse many types of murine and human cancer cells at concentrations 5-10-fold lower than normal human cells . Because of their selectivity, broad spectrum, low degree of bacterial resistance and ease of chemical synthesis, magainins are being developed as human therapeutic agents . The most advanced candidate is MSI-78, a 22-residue magainin analogue . This peptide is currently in human Phase IIb/III clinical trials in studies intended to evaluate its efficacy as a topical agent for the treatment of impetigo . Preclinical studies have demonstrated that analogues of magainin exhibit activity in vivo against malignant melanoma and ovarian cancer cells in mouse models . Intravenous administration of several magainin analogues has been shown to treat effectively systemic Escherichia coli infections in the mouse.

Ciba Found Symp, 1994, 186, 123 - 32; discussion 132-4
Function of antimicrobial proteins in insects; Natori S; We have isolated and characterized various antimicrobial proteins from the haemolymph of Sarcophaga peregrina (flesh fly) larvae . Of these the sarcotoxin I family is a group of proteins mainly active against Gram-negative bacteria whereas sapecin is active mainly against Gram-positive bacteria . In addition to its function in defence, sapecin also plays a role in insect development . Recently, we identified a hendecapeptide of the sapecin homologue sapecin B that has the same antibacterial activity as the original sapecin B . Both sarcotoxin I and sapecin are inducible proteins synthesized de novo by the fat body and/or haemocytes and secreted into the haemolymph when the insect is in the acute phase response to bacterial infection . Antifungal protein (AFP) is constitutively present in the haemolymph and is active against certain fungi but not bacteria . These various antimicrobial proteins interact with microbial membranes . Sarcotoxin I interferes with membrane functions such as ATP synthesis and amino acid transport . The fungicidal activity of AFP is enhanced synergistically by sarcotoxin I, although sarcotoxin I alone has no appreciable antifungal activity . It is clear that the flesh fly has the ability to mount a potent defence response against microbial parasites by mobilizing several antimicrobial proteins.

Adv Exp Med Biol, 1994, 357, 71 - 90
The effects of lactoferrin on gram-negative bacteria; Ellison RT 3rd; Lactoferrin is an iron-binding protein found in human mucosal secretions as well as the specific granules of polymorphonuclear leukocytes . A variety of functions have been ascribed to the protein, and it appears to contribute to antimicrobial host defense . In particular, it has been shown to have direct effects on pathogenic microorganisms including bacteriostasis and the induction of microbial iron uptake systems . Still its overall physiologic role remains to be defined . It has appeared logical that antimicrobial activity of the protein arises from sequestration of environmental iron thereby causing nutritional deprivation in susceptible organisms . This argument is buttressed by the finding that selected highly virulent pathogens have evolved techniques to subvert this effect and use the protein as an iron source . However, recent observations indicate that the protein has additional properties that contribute to host defense . Work by several groups has shown that the protein synergistically interacts with immunoglobins, complement, and neutrophil cationic proteins against Gram-negative bacteria . Further, both the whole protein and a cationic N-terminus peptide fragment directly damage the outer membrane of Gram-negative bacteria suggesting a mechanism for the supplemental effects . This review will summarize these diverse observations with a consideration of how the in vitro work relates to the physiological role of the protein.

Adv Exp Med Biol, 1994, 357, 209 - 18
Antimicrobial peptides of lactoferrin; Tomita M et al.; Lactoferrin was found to contain an antimicrobial sequence near its N-terminus which appears to function by a mechanism distinct from iron chelation . Antimicrobial peptides representing this domain were isolated following pepsin cleavage of human lactoferrin and bovine lactoferrin . The antimicrobial sequence was found to consist mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin . The identified domain contains a high proportion of basic residues, like various other antimicrobial peptides known to target microbial membranes and it appears to be located on the surface of the folded protein allowing its interaction with surface components of microbial cells . The isolated domain, "lactoferrin", was shown to have potent broad spectrum antimicrobial properties and its effect was lethal causing a rapid loss of colony-forming capability . Such evidence points to the conclusion that this domain is the structural region responsible for the microbicidal properties of lactoferrin . The evidence also suggests the possibility that active peptides produced by enzymatic digestion of lactoferrin may contribute to the host defense against microbial disease.

Br J Neurosurg, 1994, 8(6), 725 - 30
An evaluation of the epileptogenic properties of a rifampicin/clindamycin-impregnated shunt catheter; Abed WT et al.; A process has been developed by which ventriculoperitoneal hydrocephalus shunts, which are prone to bacterial colonisation, can be impregnated with antimicrobials in order to confer antibacterial activity . Concern that their use might be associated with an increased risk of postoperative seizures has been addressed here . Using two rat models, namely pentylenetetrazole (PTZ) and maximal electroconvulsive seizure (ECS) thresholds, the possible epileptogenic characteristics of the shunt catheters were determined . Animals implanted with impregnated catheters exhibited no significant difference in PTZ seizure threshold compared with controls . In contrast, the ECS threshold test showed an enhancement in seizure susceptibility in the non-impregnated catheter group, in accordance with that found in human subjects, but a significant reduction in the impregnated catheter group at 2 and 28 days, postoperatively . These data suggest that the use in human subjects of shunts impregnated with these antimicrobials will not increase the risk of postoperative seizures.

Biotechnol Ther, 1994, 5(1-2), 1 - 13
Granulocyte-macrophage colony-stimulating factor after autologous marrow transplantation for Hodgkin's disease; Klingemann HG et al.; Recombinant yeast-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 10 patients after autologous bone marrow transplantation for Hodgkin's disease given as a 24-h continuous intravenous infusion from the day of marrow infusion until the patient had obtained an absolute neutrophil count of 1.5 x 10(9)/L for 2 consecutive days or until day 30, whichever occurred first . Results were compared with results from 18 historical control patients who did not receive GM-CSF but were otherwise treated in a similar fashion . The infusion of GM-CSF led to a significantly faster neutrophil and monocyte recovery compared to the patients in the historical control group . The median days to achieve an absolute neutrophil count for the GM-CSF group and the control group were 0.5 x 10(9)/L; 9.5 and 14 days; 1.0 x 10(9)/L: 10 and 18 days; 1.5 x 10(9)/L: 11 and 29 days . No significant difference was found with respect to platelet engraftment and red cell transfusion requirements . GM-CSF therapy was discontinued at a median of 12 days . Hospitalization was also shorter for the GM-CSF group (22.5 vs . 26.5 days) and no patient in the GM-CSF group had to be readmitted after initial discharge . The incidence of documented infections was similar among both patient groups and no difference was noted in terms of antimicrobial usage . Some side effects occurred with the continuous infusion of GM-CSF, particularly fluid retention, dyspnea, fever, diarrhea, and bone pain leading to early discontinuation of GM-CSF in 2 patients . The data suggest that a continuous 24-h infusion of GM-CSF significantly accelerates myeloid engraftment, leading to earlier discharge from the hospital.

Stem Cells, 1994, 12 Suppl 1, 229 - 39; discussion 239-40
Future uses of granulocyte-macrophage colony-stimulating factor (GM-CSF); Jones TC; Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used extensively to restore hematopoietic system function after damage by diseases such as myelodysplastic syndrome or by cytotoxic anti-cancer agents used during cancer chemotherapy or prior to bone marrow transplantation . The clinical benefits of this approach have included fewer infections, fewer hospital days and less antibiotic use . In the future, the use of GM-CSF will be focused on special situations within these general areas, plus new directions that were not previously given sufficient attention . Examples of focused approaches include the use of GM-CSF in the control of fungal or protozoal disease and to take advantage of anti-tumor effects of myeloid cell activation . The anti-microbial effects will also be explored in patients who are not neutropenic but have serious infections which may be benefited by increased stimulation to myeloid cell function . The use will also be focused on mobilization of peripheral blood progenitor cells and in cycling of normal hematopoietic and malignant cells . The new directions will include use of GM-CSF by local application in healing of cutaneous ulcers, rapid wound closure and skin grafting . Because of its potent effects on immunologic mechanisms of antigen presentation, it will be used in several ways as a vaccine adjuvant . This adjuvant action will be directed at enhancing immunologic responses to antimicrobial antigens and anti-tumor antigens . The future of GM-CSF as a tool for hematopoietic and immunologic stimulation with resulting important clinical benefits is clear.

Acta Vet Scand, 1994, 35(4), 389 - 94
Sensitivity of certain porcine and bovine mycoplasmas to antimicrobial agents in a liquid medium test compared to a disc assay; Friis NF et al.; The sensitivity of some porcine and bovine mycoplasmas to potent antimicrobial agents was examined . Minimal inhibitory concentration (MIC) values were estimated for M . hyosynoviae, M . hyopneumoniae, M . dispar and M . bovis against enrofloxacin, lincomycin, tetracycline, tiamulin and tylosin, in a liquid medium test and in a disc assay . All 6 examined strains of each species and the respective type strains were significantly inhibited . The greatest sensitivity was noted for tiamulin against strains of M . hyosynoviae with a final MIC50 broth value of 0.025 micrograms ml-1 and disc value of 0.03 microgram per disc . Enrofloxacin was found very potent against M . hyopneumoniae with a final MIC50 of 0.025 microgram ml-1 and 0.1 microgram per disc, and for M . dispar with 0.05 microgram ml-1 and 0.03 microgram per disc . Most disc assay estimates in micrograms per disc were similar to or moderately greater than corresponding final broth figures in microgram ml-1 . It may be possible to convert observed disc assay values into representative final broth MIC values for use in the clinic.

Medicina (B Aires), 1994, 54(5 Pt 2), 596 - 604
{Bacterial genotyping in nosocomial infections}; Catalano M; Hospitalized patients are at unusually high risk of infections, and furthermore, the hospital environment favors the acquisition of resistance to antimicrobial agents, complicating the treatment of nosocomial infections due to drug-resistant pathogens . The prevention of nosocomial infections, based on a surveillance system as an essential element of an infection control program, is the only way to reduce morbidity and mortality . A typing method for strain clonality permits the infection control program to confirm the association between infected patients and the reservoir for the microorganisms of interest and to determine modes of transmission, because the mode of transmission or reservoir may not be the same for multiple strains of a bacterial species . An ideal method of subtyping bacterial isolates from a given species should be simple, rapid, sensitive and discriminatory . Traditionally, once bacterial isolates from an outbreak have been determined to be of the same species, further evaluation for similarity or relatedness has been based on phenotypic methods . Biotyping, serotyping, phagetyping, and antibiotype determination are not always adequately sensitive to distinguish unrelated strains with similar phenotypes . Within phenotypic methods, multilocus enzyme electrophoresis is a powerful tool but because of its complexity it is not likely to become widely available for study of local outbreaks of bacterial infections . In recent years, molecular genetic methods, including plasmid profile, genomic restriction fragment length polymorphism analyses by conventional electrophoresis or by pulsed-field gel electrophoresis, single chromosomal gene polymorphism by DNA hybridization or by PCR amplification, ribotyping, and genomic fingerprinting generated by repetitive element sequence-based polymerase chain reaction, have been useful in evaluating endemic infections and outbreaks of a variety of nosocomial pathogens . For epidemiologic studies, genotyping systems based on defined chromosomal genes or whole DNA polymorphism provide significant advantages over plasmid analysis . Among plasmid-non-based genotypic methods, the choice depends on i) the examination of how much discrimination the method can add for the epidemiologic investigation, ii) the resources available to the laboratory, and iii) the level of expertise of the personnel involved in the testing because, until standardized rules of interpretation are published, the same data may be interpreted in different ways by different investigators . Finally, biotyping, serotyping, and antibiotype determination remain an appropriate first step for the evaluation of apparent outbreaks with the caveat that different strains with the same phenotypic properties may exist concurrently within the same environment . Genotyping may be a second level of analysis to evaluate relatedness of bacterial strains, because the use of molecular biology techniques should support an epidemiologic investigation rather than initiate it.

Medicina (B Aires), 1994, 54(5 Pt 1), 439 - 58
{Review of oral cephalosporins . Basis for a rational choice}; Forti IN; During the last 10 years, the emergence and spread of the most important and common resistant pathogens isolated from clinical infections led to the great release of new antibacterial agents . Many of new orally administered antibiotics introduced, such as newer fluoroquinolones or cephalosporins, showed a spectrum of activity and clinical efficacy for the most common clinical community infections . Therefore, therapeutic indication of a new cephalosporin is somewhat difficult to define, because the newer drugs must compete with improved properties over the previous ones . Therefore, choice of a first line antibiotic among apparently therapeutic equivalents could become questionable . The aim of this review was to compile the available data to offer help for a rational choice in confirmed infections of every particular patient condition and context based on microbiological activity, pharmacokinetic properties, clinical efficacy, safety and cost . Orally administered cephalosporins are beta-lactamic broad-spectrum antimicrobial agents that are often used empirically to treat community bacterial infections and also to treat culture-proven infections due to selected gram-positive and gram-negative microorganisms . Cephalosporins differ widely in their spectrum of activity, in vitro antimicrobial potency, microbial resistance, pharmaco-kinetic properties and cost . These differences result from modifications of the cephalosporin molecule . The substitutions on the R1, R2, R3 or R4 side chains results in changes in antimicrobial spectrum, potency, bioavailability, half-life and profile of toxicity . In general, the first-generation agents are more active against gram-positive organisms, more susceptible to B-lactamases of gram-negative producers, shorter serum half-life and lower cost than the other agents . The second-generation cephalosporins present enhanced spectrum of activity due to increased resistance to beta-lactamase enzymes and have longer serum half-life . The third-generation agents are the most active against Entero-bacteriaceae, possess a superior beta-lactamase stability against selected enzymes of multiple resistant bacteria, improved pharmacokinetic properties with extended plasma half-life, that permit once or twice daily administration and are the most expensive compared with the previous drugs . Among these new oral cephems, the addition of an ester group enhances the oral absorption from the gastrointestinal tract and provides better bioavailability as well as antimicrobial activity . The development of bacterial resistance has affected all steps of the cephalosporin mechanism of action . Expertise in the choice and use of the cephalosporins will remain a challenge for the physician, as additional investigational cephalosporins will continue to be developed and introduced into clinical practice in the near future.

Klin Khir, 1994, (3), 14 - 6
{A new sorbent used for preparing the intestines for a surgical intervention}; Rudichenko VM et al.; A new sorbent with a high sorptive capacity and antimicrobial properties against different species of microorganisms (aerobic and anaerobic) is suggested . Its effectiveness has been proved both in vitro and in vivo . The authors consider that the sorbent can be recommended for clinical trials with the aim of its use in preparation of the intestine for the operation.

Eur J Surg Suppl, 1994, (573), 67 - 72
Assessing cost effectiveness of antimicrobial treatment: monotherapy compared with combination therapy; Davey PG et al.; The obvious costs of antibiotic treatment include drugs, equipment with which to give them, and assays . Less obvious, but more important, are the costs of quality control to ensure safe and effective treatment . The more complex the regimen, the more expensive the quality control . None the less, there is considerable variation in both assay price and number of assays/patient . Our data show that the drug costs of a regimen such as ampicillin plus gentamicin plus metronidazole are outweighed by the costs of quality assurance to prevent drug toxicity and charges of malpractice . Trials show that monotherapy with various beta-lactams is more cost effective than aminoglycoside combinations for surgical infections . Compounds such as piperacillin/tazobactam, a new beta-lactam/beta-lactamase inhibitor combination that is classed as monotherapy, have the potential to solve many of these economic problems . Several completed and continuing clinical studies are showing that monotherapy is as effective as combination treatment . Cost studies in the future are likely to confirm the economic advantages of monotherapy.

Ann Trop Paediatr, 1994, 14(1), 65 - 9
Hirschsprung's disease in Zaria, Nigeria: comparison of 2 consecutive decades; Nmadu PT; This is a retrospective study of 136 histologically confirmed cases of Hirschsprung's disease (HD) seen and treated in a single centre over 2 consecutive decades spanning the years from 1972 to 1991 . Forty-six cases were seen in the 1st 10 years and 90 in the 2nd . Certain factors were considered to be responsible for the observed improvement during the 2nd decade; these included improvements in the mode of bowel preparation, the use of more effective antimicrobial agents with a wider spectrum of activity for prevention and treatment of established infections, and improvements in the pre-operative nutritional status of the patients and in the staging of the operations . Morbidity was minimal . Mortality dropped from 28.3% in the 1st decade to 5.6% in the 2nd . Causes of mortality in the 1st decade were pneumonia (8), aspiration of gastric contents (2), undernutrition (2) and haemorrhage from a dislodged clamp several days following a Duhamel procedure (1) . In the early part of the 2nd decade, three patients died from anastomotic dehiscence following the Swenson procedure and two from aspiration pneumonia.

Ann Oncol, 1994, 5 Suppl 2, 127 - 32
Cost-benefit of granulocyte colony-stimulating factor administration in older patients with non-Hodgkin's lymphoma treated with combination chemotherapy; Zagonel V et al.; BACKGROUND: Older patients with non-Hodgkin's lymphoma (NHL) display a poorer response to chemotherapy and a significantly higher treatment-associated toxicity than do younger individuals . We investigated the potential clinical benefits and the cost-effectiveness of accelerated granulocyte recovery induced by recombinant granulocyte colony-stimulating factor (G-CSF) in patients with aggressive NHLs, aged 60-70 years, during treatment with a second-generation combination chemotherapy . PATIENTS AND METHODS: 12 consecutive patients (median age 66 years) treated with six to eight courses of CHVmP/VB plus subcutaneous G-CSF (5 micrograms/kg/day) were compared with 11 consecutive subjects (median age 65 years) who received the same chemotherapy regimen without growth factor support . The two groups of patients were fully comparable as to the clinicopathologic features . A comparative analysis of treatment costs (including hospitalization, antimicrobial prophylaxis and therapy, supportive and diagnostic procedures, and G-CSF) was also performed . RESULTS: Both the overall response rate and the percentage of complete remissions were comparable in the two treatment groups . In the control group, 32.5% of chemotherapy courses were delayed, as opposed to 19% in the G-CSF group (p = 0.05) . The mean duration of delay for patients receiving or not receiving G-CSF was 10.1 and 25.9 days, respectively (p = 0.02) . Grade 3 and 4 granulocytopenia complicated 27.7% of chemotherapy courses in control patients and only 4.8% in subjects receiving G-CSF (p < 0.001) . Similarly, severe infections and mucositis were significantly higher in patients receiving chemotherapy alone (15.6% and 3.6%, respectively) compared to the G-CSF group (4.8%, p = 0.01; p = 0.04, respectively) . A mean of 1.1 days/course of hospitalization was required in the control group, as opposed to 0.2 days/course in patients receiving G-CSF (p = 0.05) . Although overall treatment costs were higher in the control group, single cost of the recombinant growth factor exceeded by far all the other expenses in the G-CSF group, reaching a statistical relevance (p = 0.01) . CONCLUSIONS: The inclusion of prophylactic G-CSF in the treatment plan for aggressive NHL in older patients appears safe and cost-effective in view of the peculiar clinical features of aged subjects and the possibility of delivering effective doses of antineoplastic drugs on an outpatient setting.

Rinsho Ketsueki, 1994 Jan, 35(1), 59 - 64
{Complete remission during administration of rhG-CSF in acute myeloblastic leukemia with pneumonia}; Hayatsu K et al.; A 54-year-old man was admitted with pneumonia and pancytopenia (WBC 400/microliters, RBC 297 x 10(4)/microliters, Hb 10.1g/dl, Plt 5.6 x 10(4)/microliter) . Bone marrow aspiration revealed a proliferation of leukemic cells (61.6%) and led the diagnosis of AML (M2) . Although no antileukemic agent had been administered previously, the combination therapy of antimicrobials and rhG-CSF for the infection not only improved pneumonia, but also induced a complete remission of AML . The short-term remission was followed by the first relapse of AML, in spite of the continuous administration of rhG-CSF . The abnormal karyotype (47, XY, +8) shown in the chromosomal analysis of the bone marrow cells at admission remained on the first remission . The second complete remission was induced by combination chemotherapy (BHAC-DMP), and the chromosomal analysis at this time showed a normal karyotype . These findings suggested that the first remission of AML in this case was caused mainly by the maturation induction effect of rhG-CSF on the leukemic cells, however, the possibility of the spontaneous remission in this case also remained.

J Infect Dis, 1994 Jan, 169(1), 119 - 26
O, K, and H antigens predict virulence factors, carboxylesterase B pattern, antimicrobial resistance, and host compromise among Escherichia coli strains causing urosepsis; Johnson JR et al.; The O:K:H serotypes of 75 Escherichia coli blood isolates from patients with urosepsis were compared for the presence and expression of determinants for P fimbriae, hemolysin, and aerobactin; antimicrobial resistance; the carboxylesterase B phenotype; and associated compromising host conditions . O groups, K types, and O:K:H serotypes previously associated with urovirulence accounted for 69%, 60%, and 31% of the population, respectively . Chromosomal determinants for P fimbriae, hemolysin, and aerobactin were present in combination more commonly among strains belonging to urovirulence-associated O groups, K types, and O:K:H serotypes . Similarly, antimicrobial resistance was strikingly less prevalent, the B2 carboxylesterase phenotype more common, and associated host compromise less common among such strains . These data demonstrate that the O groups, K types, and O:K:H serotypes traditionally associated with urovirulence are prominent among E . coli strains causing urosepsis, in which they are associated with presence and expression of multiple chromosomal virulence factor determinants, susceptibility to antimicrobial agents, the B2 carboxylesterase phenotype, and noncompromised hosts.

Nature, 1993 Dec 23-30, 366(6457), 748 - 51
Potential virulence determinants in terminal regions of variola smallpox virus genome; Massung RF et al.; Smallpox eradication culminated the most successful antimicrobial campaign in medical history . To characterize further the linear double-stranded DNA genome of the aetiological agent of smallpox, we have determined the entire nucleotide sequence of the highly virulent variola major virus, strain Bangladesh-1975 (VAR-BSH; 186,102 base pairs, 33.7% G + C; Genbank accession number, L22579) . Here we highlight features of the molecule and focus on a few of the 187 putative proteins that probably contribute to pathogenicity and virus host-range properties . One hundred and fifty proteins were markedly similar to those of vaccinia virus (smallpox vaccine), for which a complete sequence has been reported for strain Copenhagen (VAC-CPN; 191,636 base pairs, 33.3% G + C) . The remaining 37 proteins reflected variola-specific sequences or open reading frame divergences for variant proteins, which are often truncated or elongated compared with their vaccinia counterparts.

J Neurosci Res, 1993 Dec 15, 36(6), 657 - 62
Bactenecin, a leukocytic antimicrobial peptide, is cytotoxic to neuronal and glial cells; Radermacher SW et al.; Small antimicrobial peptides are abundantly produced by leukocytes . These peptides are active against a broad range of pathogens, notably bacteria, fungi, and enveloped viruses, but hardly anything is known about their physiological and pathophysiological relevance . We observed that bactenecin, a dodecapeptide, is strongly cytotoxic to rat embryonic neurons, fetal rat astrocytes and human glioblastoma cells . This neurotoxicity is unique to bactenecin, as a panel of antibacterial peptides from vertebrates and invertebrates, like defensins, corticostatin, indolicidin, cecropin P1, tachyplesin I, the magainins, or apidaecins did not impair neuronal viability.

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