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PubMed1981

Side effects of antibiotics.

A review of the side effects of antibiotics in human patients is presented. At least three classes of untoward reactions may be distinguished: development of drug hypersensitivity, toxicological hazards, and microbial effects such as emergence of drug resistance. The intrinsic toxicitiies of the oldest discoveries, penicillin, penicillin and sulphonamides, have turned out to be very low for most animals as well as for man. These agents interfere with specific synthetic pathways in bacteria which are absent in mammals. The antibiotics discovered next (streptomycin and other amino-glycosides; chloramphenicol; tetracyclines) have all been shown to display, under certain circumstances various types of sometimes serious toxicities. As with thalidomide, the nature of their toxic effects had not been predicted by animal experiments. The present set of medically optimum antibiotics has its origin largely in substances with a long medical tradition. They represent the result of close cooperation of medical and scientific men of various disciplines. For the near future it seems unlikely that antimicrobial drugs will enter human and animal environments while yet tainted with any of the unforeseen side effects revealed in the past. Admirable work very recently carried out in the Institute of professor van Genderen shows that he never lost interest in the group of drugs that he so successfully explored when he was still on the staff of the institute where he started his career.

Animals↗
PubMed1984

Microbial factors in contact lens fitting.

As contact lens practitioners, optometrists work in a nonsterile environment and on a nonsterile part of the human body. Our report describes 10 cases of eye infection related to contact lens wear. Practitioners need to be aware of the problems which can occur when a thoroughly sterilized contact lens is placed on an unsterile and biologically complex eye. We recommend taking swabs of the conjuctiva in all eyes where ocular inflammation is present. In those areas in which the professions of optometry and medicine meet, cooperation should exist. Improving our knowledge and skills in microbiology helps to facilitate such cooperation. Our experience has been most rewarding and interaction in this field with medical practitioners has been positive. The use of a high quality slitlamp is essential.

Acinetobacter Infections↗
PubMed1998

Ocular levels of azithromycin.

OBJECTIVE: To assess azithromycin levels in human serum, aqueous humor, tear fluid, and conjunctival tissue specimens after administration of a single 1-g oral dose of azithromycin. METHODS: Sixty patients undergoing cataract surgery were included in this analysis. Serum, aqueous, and tear specimens were collected 3, 6, and 12 hours and 1, 2, 3, and 4 days after azithromycin administration. Conjunctival tissue biopsy specimens were collected 1, 2, 3, 4, 6, 8, 10, 12, and 14 days after azithromycin administration. All specimens were subjected to analysis by high-performance liquid chromatography-mass spectrometry. RESULTS: Azithromycin concentration ranges during the specified sampling times were as follows: serum, 21 to 974 ng/mL; tear, 82 to 2892 ng/mL; aqueous, 10 to 69 ng/mL; and conjunctival, 0.7 to 32 micrograms/g. Levels above the 90% minimal inhibitory concentration (MIC90) for Chlamydia trachomatis were detected after 4 days in all tear samples and after 14 days in all conjunctival tissue specimens following oral azithromycin administration. CONCLUSION: We demonstrated prolonged high levels of azithromycin in drug-targeted ocular tissue. Prolonged high concentrations of azithromycin in conjunctival tissue make this drug suitable for treatment of conjunctivitis caused by chlamydiae and other susceptible organisms.

Administration, Oral↗
PubMed1992

Preparation and in vitro and in vivo evaluation of quinolones with selective activity against gram-positive organisms.

A series of quinolones were prepared which contained oximes or substituted oximes as replacements for the amine substituents normally found on the pyrrolidine or piperidine fragments of quinolone antibacterial agents. These substituents led to compounds that had selective activity against Gram-positive organisms. These compounds showed in vivo activity against Staphylococcus aureus. Only compound 29 had in vivo activity against Streptococcus pneumoniae.

4-Quinolones↗
PubMed2004

A European perspective on intravascular catheter-related infections: report on the microbiology workload, aetiology and antimicrobial susceptibility (ESGNI-005 Study).

The laboratory workload, microbiological techniques and aetiology of catheter-related infections in European hospitals are mostly unknown. The present study (ESGNI-005) comprised a 1-day (22 October 2001), laboratory-based, point-prevalence survey based on a questionnaire completed by microbiology laboratories in European (European Union (EU) and non-EU) hospitals. Also included were questions requesting retrospective information for the year 2000. In total, 151 hospitals from 26 European countries participated, of which 78.1% were teaching institutions. Overall, the estimated population served by these institutions was 121,363,800, and the estimated number of admissions during 2000 was 6,712,050. The total number of catheter tips processed during 2000 was 142,727, or 21/1,000 admissions, of which 23.7% were considered to be positive in the institutions using semiquantitative or quantitative techniques. Overall, EU centres received significantly more catheter tip samples/1,000 admissions and had a significantly higher rate of 'positivity' (p < 0.0001) than non-EU centres. Of the institutions surveyed, 11.4% (7.2% in EU countries and 23.7% in non-EU countries; p 0.04) used only qualitative techniques for catheter tip sample processing. On the day of the study, 167 microorganisms were recovered from significant catheter tip cultures (122 patients), of which Gram-positive bacteria represented 70.7%, Gram-negative bacteria 22.2%, and yeasts 7.2%. The five most common microorganisms were coagulase-negative staphylococci, Staphylococcus aureus, Candida spp., Enterococcus spp. and Pseudomonas spp. Overall, 19% of catheter tip cultures were polymicrobial. In the case of S. aureus, 40% of isolates were resistant to oxacillin, as were 63.4% of coagulase-negative staphylococcus isolates. Of 37 Gram-negative isolates, 35% were resistant to cefotaxime, 31% to ceftazidime, and 27% to ciprofloxacin. Imipenem and cefepime had the lowest reported rates of resistance (11%).

Anti-Bacterial Agents↗
PubMed1989

Genetic properties of plasmids isolated from pathogenic strain of Citrobacter freundii.

It was found that Citrobacter freundii SLJ10 strain was an etiological factor of swine diarrhoea in North Poland. This strain harboured a plasmid aggregate consisting of two plasmids-pEM4 responsible for virulence and pEM6 for selective advantage of the strain, determining resistance to tetracycline and production of bacteriocin. These two plasmids cooperated in conjugal transfer and formed an infective block of genetic information, which could be transferred to other strains of Enterobacteriaceae and cause their virulence.

Citrobacter↗
PubMedDate not supplied

The clinical, microbial, and host response characteristics of the failing implant.

The goal of this study was to provide new data regarding levels of inflammatory and growth factor mediators and bacterial pathogens associated with failing implants, as compared to healthy implants. Twenty-one patients with failing implant sites (group 1) and 8 patients with only healthy implants (group 2) were included. Fifteen of the 21 failing implant patients (group 1) also presented with at least one stable nondiseased implant. Plaque samples were examined, using DNA oligonucleotide probes for 40 different microbes. Gingival crevicular fluid samples were collected for the analyses of catabolic bone resorbing agonists prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and IL-6 and anabolic bone-forming growth factors transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF). Although positive trends were noted, there were no significant differences in any of the microbial, inflammatory, or growth factors mediators comparing failing to stable implants in group 1. This study found greater detection frequencies of P. nigrescens, P. micros, F. nucleatum ss vincentii, and F. nucleatum ss nucleatum, as well as significant elevations in GCF levels of PGE2, IL-1 beta, and PDGF in mouths with failing implant sites as compared to mouths with healthy control implants. Risk appears to be primarily at a patient level and secondarily at a site or implant level from a clinical, microbial (P. micros and P. nigrescens), and biochemical (PGE2 and IL-1 beta) perspective. Furthermore, the counts of P. nigrescens and P. micros were found to correlate with concentrations of PGE2 at a site level.

Adult↗
PubMed2005

Synergy in cytokine and chemokine networks amplifies the inflammatory response.

The inflammatory response is a highly co-ordinated process involving multiple factors acting in a complex network as stimulators or inhibitors. Upon infection, the sequential release of exogenous agents (e.g. bacterial and viral products) and induction of endogenous mediators (e.g. cytokines and chemokines) contribute to the recruitment of circulating leukocytes to the inflamed tissue. Microbial products trigger multiple cell types to release cytokines, which in turn are potent inducers of chemokines. Primary cytokines act as endogenous activators of the immune response, whereas inducible chemokines act as secondary mediators to attract leukocytes. Interaction between exogenous and endogenous mediators thus enhances the inflammatory response. In this review, the synergistic interaction between cytokines to induce chemokine production and the molecular mechanisms of the cooperation amongst co-induced chemokines to further increase leukocyte recruitment to the site of inflammation are discussed.

Animals↗
PubMed1999

Discovery and development of antineoplastic agents from natural sources.

Nature has provided many effective anticancer agents in current use, such as the microbially derived drugs; dactinomycin; bleomycin and doxorubicin; and the plant-derived drugs, vinblastine, irinotecan, topotecan, etoposide, and paclitaxel. The search for novel antitumor agents from natural sources continues through collaboration among scientists worldwide in the investigation of coral reefs, rainforests, and deep subsurface thermal vents for novel bioactive compounds. The potential for drug discovery is being further enhanced by recent advances in procedures for microbial cultivation and the extraction of nucleic acids from environmental samples, resulting in the identification of novel microbes that provide a vast untapped reservoir of genetic and metabolic diversity. Manipulation of the biosynthetic pathways of microbial polyketides through genetic engineering permits the biosynthesis of bioactive polyketides not generated naturally.

Animals↗
PubMedDate not supplied

[Relation of DNA replication and cell division frequency in a population of microorganisms to the cell growth rate].

DNA replication and the frequency of cell division were studied in a microbial population in relation to the rate of cell growth. The relationship is based on the law of cell biomass linear increase during the cell cycle and on the exponential law of mean cell mass increase, and depends on the specific rate of population growth. The cell mass in the initiation of DNA replication is correlated with the number of initiation points basing on the Cooper-Helmstetter theory of DNA replication and taking account of the linear growth of mass in one cell. Possible applications of these relationships are discussed.

Bacillus subtilis↗
PubMed2026

Deciphering the genetic background of an industrial 2-ketogluconic acid-producing strain Pseudomonas plecoglossicida JUIM01 using whole-genome sequencing.

2-Ketogluconic acid (2KGA) is an important precursor for the food antioxidant erythorbic acid, currently produced via microbial fermentation using Pseudomonas species. To facilitate the genetic improvement of production strains, the complete genome of an industrial 2KGA producer P. plecoglossicida JUIM01 was sequenced and analyzed. The genome consists of a 5.13-Mb circular chromosome with a GC content of 63.58%, encoding 4,517 predicted proteins. Comprehensive functional annotation identified a putative global regulatory network comprising 75 core regulators, which were classified into six functionally cooperative modules, potentially governing the strain's metabolism and environmental adaptability.&#xa0;We further delineated the genetic determinants hypothetically linked to efficient 2KGA synthesis, including glucose metabolism, fatty acid metabolism, and the oxidative phosphorylation system.&#xa0;These outputs could provide the genomic resource for elucidating high productivity and robustness, and rationally engineering the high-performance chassis cells toward robust 2KGA production.

P. plecoglossicida↗
PubMed1985

The identification of candidate antigens for the development of birth control vaccines. An international multi-centre study on antibodies to reproductive tract antigens, using clinically defined sera.

In an attempt to identify appropriate antigens for birth control vaccines, the Task Force on Immunological Methods for Fertility Regulation under WHO's Special Programme of Research, Development and Research Training in Human Reproduction carried out an investigation of naturally occurring immune responses to reproductive tract antigens which were consistently associated with infertility. Large volumes of sera from subjects satisfying the criteria for one of 16 different clinical categories (listed in Table 1) were collected and samples were subsequently assessed, under code, by investigators with experience in the detection of antibodies to antigens involved in the reproductive process. Sera from 329 persons were included in the study and 20 laboratories examined the sera for antibodies to sperm, zona pellucida, and trophoblast or trophoblast products. In addition, antibodies to certain microbial antigens and to various leucocyte and organ antigens were investigated. The results of these studies are presented in the following papers.

Antibodies↗
PubMed1991

Growth hormone and insulin-like growth factor I regulate collagen gene expression and extracellular collagen in cultures of avian skin fibroblasts.

Avian skin fibroblasts were isolated, cultured and incubated with [3H]proline for 24 h. The cells exported radiolabeled collagenase-digestible (CDP) and non-collagenase-digestible (NCDP) proteins into the medium. Human, bovine and avian growth hormone (GH) as well as insulin-like growth factor I (IGF-I) attenuated the appearance of [3H]CDP in the medium without affecting [3H]NCDP. The appearance of [3H]CDP was not affected by prolactin. The effects of GH and IGF-I were enhanced by increasing concentrations of fetal calf serum (FCS). A synergism was observed between GH and IGF-I in their effect on CDP. Each peptide, at an ineffective concentration, increased the sensitivity of the cells to the other peptide. Collagenase activity in the medium was enhanced by IGF-I, but not modified by GH, FCS, or by their interaction with IGF-I. GH and IGF-I inhibition of type I procollagen gene expression was demonstrated with the aid of probes containing sequences corresponding to the mRNAs for avian alpha I and alpha II chains. The results suggest that GH and IGF-I cooperate in regulating collagen synthesis, but collagen degradation is affected by IGF-I and not by GH.

Animals↗
PubMed1995

Clinical correlates of anaerobic bacteriology in peritonitis.

Recent surgical reports indicate that for patients with secondary bacterial peritonitis, surgeons do not routinely use the identification of the bacterial pathogens and determination of their antimicrobial susceptibilities in choosing antimicrobial therapy. Further, some surgeons advocate abandoning the routine practice of obtaining culture specimens from patients with complicated appendicitis, because the data from the clinical laboratory have not been found to have an impact on postoperative care. We review the rationale for continued surveillance of and implementation of bacteriological data in treatment of secondary peritonitis. We also describe in detail the anaerobic flora of secondary peritonitis, the unique susceptibility patterns of these organisms, and the specific virulence factors of anaerobes, particularly Bacteroides fragilis. The fact that clinical investigations sometimes result in treatment failure when gram-negative anaerobes are resistant to the antimicrobials used or when complete antimicrobial susceptibility data are not available emphasizes the need for accurate and early knowledge of the bacteriologic characteristic of the flora of the operative site. We emphasize the relationship of in vitro susceptibility of intraoperative isolates with clinical outcome. We propose a cooperative trial that would demonstrate that successful antimicrobial therapy should be based on the susceptibility of the flora of the operative site, which correlates with clinical outcome.

Animals↗
PubMed1980

Lethal effect of a heterologous murein hydrolase on penicillin-treated Streptococcus sanguis.

Nine strains of Streptococcus sanguis exhibited tolerance to benzylpenicillin: the growth of each strain was susceptible to penicillin with minimal inhibitory concentrations of 0.1 mug/ml or lower, but the bacteriolytic and bactericidal effects were limited in each case. The tolerance of these bacteria was also reflected in the large discrepancies between the minimal inhibitory and minimal bactericidal concentrations for benzylpenicillin. The hypothesis that a natural deficiency of endogenous murein hydrolase (autolysin) in this species accounts for the penicillin tolerance was tested by using a heterologous murein hydrolase, the C-phage-associated lysin. In seven of the strains, addition of the lysin to the culture together with penicillin or other cell wall inhibitors resulted in lysis and rapid loss of viability. The enzyme alone did not appreciably affect normally growing cultures. The irreversible effects of penicillin plus lysin were drastically reduced in the presence of the bacteriostatic agents chloramphenicol and cerulenin. Speculations based on experiments are presented for the mechanisms by which penicillin treatment sensitizes these bacteria to an exogenous lytic enzyme. Similar phenomena requiring cooperation of host factors and penicillin may occur during infection, since somewhat similar although less pronounced results were obtained by addition of human lysozyme to penicillin-treated S. sanguis.

Amidohydrolases↗
PubMed1980

Automated detection of microbial growth in blood cultures by using stainless-steel electrodes.

Sterile stainless-steel electrodes implanted in blood culture bottles and monitored electronically were used to detect growth of microorganisms. Each blood culture bottle contained 100 ml of medium and was inoculated with 10 ml of blood seeded with either 300 or 50 colony-forming units of one of several bacterial or yeast species that are commonly isolated from clinical blood cultures. Growth was indicated by a voltage change of at least 0.1 mV/min with an increasing slope over at least three consecutive 15-min intervals. This method was compared to the conventional visual method for detecting microbial growth in broth. Growth detection by both techniques was confirmed by subculture to solid media. Of the 163 cultures seeded with the high inoculum (300 colony-forming units) and confirmed as being positive, 148 (90.8%) were positive by the electronic detection system (EDS). At the lower inoculum (50 colony-forming units), 47 of 53 (88.7%) positive cultures were detected by EDS. Twelve of the 21 false-negatives by the EDS were cultures seeded with Cryptococcus neoformans. Excluding C. neoformans, the rate of detection of growth was 96.0%. Microbial growth was detected an average of 18 h earlier by EDS than by the conventional system in 176 (90.2%) of the cultures. Also examined were 156 patient blood cultures: 13 were positive both by EDS and by conventional methods.

Bacteria↗
PubMed1998

Sporadic emergence of Klebsiella pneumoniae strains resistant to cefepime and cefpirome in Greek hospitals.

The sporadic emergence of Klebsiella pneumoniae strains resistant to cefepime and cefpirome was observed in Greek hospitals during 1996. Examination of six epidemiologically distinct strains and clones selected in vitro provided indications that resistance is due to the cooperation of decreased outer membrane permeability and hydrolysis of the cephalosporins by SHV-5 beta-lactamase, which was produced in large amounts.

Cefepime↗