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 w