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PubMedDate not supplied

Two-day induction with thymoglobulin in kidney transplantation: risks and benefits.

INTRODUCTION: The aim of this study was to develop an induction protocol to reduce allograft rejection with fewer posttransplant infections and malignancies. METHODS: In this prospective randomized study, a T- and B-cell depletion protocol, consisting of IV thymoglobulin (ATG 5 mg/kg/d) plus methylprednisolone (500 mg/d) plus azathiopurine (2 mg/kg/d), was on days 0 and 1 after renal transplantation. CyA was introduced at day 3.39 among patients undergoing either primary living related (n = 16) or cadaveric (n = 23) transplants excluding recipients of full-HLA-matched sibling, or five- and six-HLA-matched cadaveric donor kidneys. The adequacy of immunosuppression was evaluated by flow cytometric analysis for total, CD3+ (T-cell), and CD19+ (B-cell) lymphocytes. RESULTS: The acute rejection rate was 6% and 37/39 patients are alive with functioning grafts at an average follow-up of 14.5 months. The overall patient and graft survival rate was 95%. Their mean creatinine value was 1.27 mg/dL. Six patients (16%) required hospitalization due to serious infections. The two deaths were attributed to septicemia and brain abcess caused by unusual agents, namely, Rhodococcus equi and Sporobolomyces. One patient presented with a cutaneous Kaposi sarcoma in the 11th month posttransplant. CONCLUSION: A Two-day induction protocol with thymoglobulin yields acceptable acute rejection rates among renal transplants. However, caution is necessary for adverse events, particularly atypical bacterial and fungal infections.

Adolescent↗
PubMed2004

Construction and application of a bovine immune-endocrine cDNA microarray.

A variety of commercial DNA arrays specific for humans and rodents are widely available; however, microarrays containing well-characterized genes to study pathway-specific gene expression are not as accessible for domestic animals, such as cattle, sheep and pigs. Therefore, a small-scale application-targeted bovine immune-endocrine cDNA array was developed to evaluate genetic pathways involved in the immune-endocrine axis of cattle during periods of altered homeostasis provoked by physiological or environmental stressors, such as infection, vaccination or disease. For this purpose, 167 cDNA sequences corresponding to immune, endocrine and inflammatory response genes were collected and categorized. Positive controls included 5 housekeeping genes (glyceraldehydes-3-phosphate dehydrogenase, hypoxanthine phosphoribosyltransferase, ribosomal protein L19, beta-actin, beta2-microglobulin) and bovine genomic DNA. Negative controls were a bacterial gene (Rhodococcus equi 17-kDa virulence-associated protein) and a partial sequence of the plasmid pACYC177. In addition, RNA extracted from un-stimulated, as well as superantigen (Staphylococcus aureus enterotoxin-A, S. aureus Cowan Pansorbin Cells) and mitogen-stimulated (LPS, ConA) bovine blood leukocytes was mixed, reverse transcribed and PCR amplified using gene-specific primers. The endocrine-associated genes were amplified from cDNA derived from un-stimulated bovine hypothalamus, pituitary, adrenal and thyroid gland tissues. The array was constructed in 4 repeating grids of 180 duplicated spots by coupling the PCR amplified 213-630 bp gene fragments onto poly-l-lysine coated glass slides. The bovine immune-endocrine arrays were standardized and preliminary gene expression profiles generated using Cy3 and Cy5 labelled cDNA from un-stimulated and ConA (5 microg/ml) stimulated PBMC of 4 healthy Holstein cows (2-4 replicate arrays/cow) in a time course study. Mononuclear cell-derived cytokine and chemokine (IL-2, IL-1alpha, TNFalpha, IFN-gamma, TGFbeta-1, MCP-1, MCP-2 and MIP-3alpha) mRNA exhibited a repeatable and consistently low expression in un-stimulated cells and at least a two-fold increased expression following 6 and 24 h ConA stimulation as compared to 0 h un-stimulated controls. In contrast, expression of antigen presenting molecules, MHC-DR, MHC-DQ and MHC-DY, were consistently at least two-fold lower following 6 and 24 h ConA stimulation. The only endocrine gene with differential expression following ConA stimulation was prolactin. Additionally, due to the high level of genetic homology between ovine, swine and bovine genes, RNA similarly acquired from sheep and pigs was evaluated and similar gene expression patterns were noted. These data demonstrate that this application-targeted array containing a set of well characterized genes can be used to determine the relative gene expression corresponding to immune-endocrine responses of cattle and related species, sheep and pigs.

Animals↗
PubMed2006

Foals are interferon gamma-deficient at birth.

The increased vulnerability of foals to specific pathogens such as Rhodococcus equi is believed to reflect an innate immunodeficiency, the nature of which remains poorly understood. Previous studies have demonstrated that neonates of many species fail to mount potent Th1 responses. The current research investigates the ability of circulating and pulmonary lymphocytes of developing foals to produce interferon gamma (IFNgamma). Peripheral blood mononuclear cells (PBMC) were prepared from up to 10 horse foals at regular intervals throughout the first 6 months of life. Bronchoalveolar lavage (BAL) samples were collected at 1, 3 or 6 months of age from three groups of five foals. The PBMC and BAL cells were stimulated in vitro and IFNgamma production was measured by intracellular staining. In addition, RNA was extracted from freshly isolated and in vitro stimulated PBMC and BAL cells for quantitation of IFNgamma gene expression by real time PCR. Newborn foals exhibited a marked inability to express the IFNgamma gene and produce IFNgamma protein. This deficiency was observed in both circulating and pulmonary lymphocytes. However, IFNgamma gene expression and protein production increased steadily throughout the first 6 months of life, reaching adult levels within the first year of life. These findings suggest that foals are born with an inherent inability to mount a Th1-based cell mediated immune response which may contribute to their susceptibility to intracellular pathogens.

Age Factors↗
PubMed2005

Molecular analyses of mycobacteria other than the M. tuberculosis complex isolated from Northern Ireland cattle.

Mycobacteria other than the Mycobacterium tuberculosis complex (MOTT), isolated from Northern Ireland cattle, were identified by PCR amplification of the 16S rRNA gene, and subsequent reverse cross blot hybridisation and sequence analyses. Elucidation of the MOTT species was to facilitate specificity testing of new and existing diagnostic test reagents for bovine tuberculosis. The presence of the genes for potential diagnostic antigens: MPB70, MPB64, ESAT-6 and CFP-10 in the isolated MOTT species was investigated. Molecular analyses of cultured isolates from bovine lymph node specimens of 48 cattle identified a wide variety of mycobacterial species including Mycobacterium nonchromogenicum, Mycobacterium malmoense, Mycobacterium bohemicum, Mycobacterium paratuberculosis, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium holsaticum, Mycobacterium palustre, Mycobacterium sp. IWGMT 90210, Mycobacterium sp. LIV-2129, a potentially novel mycobacterial species (EMBL/GenBank/DDBJ Accession Number AJ617495) and Rhodococcus equi. Apart from M. kansasii, the results of traditional (standard phenotypic and biochemical) and molecular identification methods did not correlate well, with traditional methods identifying fewer species. Most of the species identified were either recognised pathogenic or potential pathogenic species. The genes for ESAT-6, CFP-10 and, unusually, MPB64 were detected in M. kansasii only. The MPB70 gene was not detected in any of the species. This study supported restricted species distribution of these genes as well as identifying a different range of MOTT species that could be included in specificity testing of new diagnostic reagents for bovine tuberculosis.

Animals↗
PubMed1997

Bacterial infections.

Non-opportunistic bacterial infections are an important cause of morbidity and mortality for HIV-infected adults and children. Factors associated with increased risk of these include altered B- and T-cell function; altered phagocytic cell function; skin and mucous membrane defects; and use of indwelling vascular catheters, antibiotics, or cytotoxic agents. The pathogens encountered most frequently are S. aureus, S. pneumoniae, H. influenzae, Salmonella sp., and Pseudomonas aeruginosa. Less commonly encountered organisms include Rhodococcus equi, Listeria monocytogenes, Shigella sp., and Nocardia asteroides, Strategies for prevention as well as diagnosis and treatment of these are discussed.

AIDS-Related Opportunistic Infections↗
PubMed2002

Antimicrobial activity of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), compared to other quinolones, against clinical isolates from cancer patients.

The in vitro spectrum of a novel des-fluoro (6) quinolone, garenoxacin (BMS-284756), was compared with that of ciprofloxacin, levofloxacin, and trovafloxacin against 736 clinical isolates from cancer patients. Garenoxacin was the most active agent overall against Gram-positive organisms, with potent activity against Aerococcus spp., Micrococcus spp., Rhodococcus equi, Stomatococcus mucilaginous, Bacillus spp., Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible Staphylococcus spp., and all beta-hemolytic and viridans streptococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae garenoxacin inhibited the majority of these isolates at <or=4.0 microg/ml, its proposed susceptibility break-point. All 4 agents had sub-optimal activity against Pseudomonas aeruginosa and variable activity against other non-fermenters, with Stenotrophomonas maltophila and Alcaligenes spp. being the most resistant isolates. The overall broad spectrum of garenoxacin warrants its evaluation for the prevention or treatment of infections in cancer patients.

Anti-Infective Agents↗
PubMed2003

In vitro antimicrobial activity of moxifloxacin compared to other quinolones against recent clinical bacterial isolates from hospitalized and community-based cancer patients.

The in vitro spectrum of moxifloxacin (a C-8-methoxyquinolone) was compared to that of ciprofloxacin and levofloxacin against 924 recent clinical isolates from cancer patients. Moxifloxacin was more active than the comparator agents against Gram-positive pathogens, with potent activity against Aerococcus spp., Listeria monocytogenes, Micrococcus spp., Rhodococcus equi, and Stomatococcus mucilaginous, methicillin-susceptible Staphylococcus spp., all beta hemolytic streptococci, viridans streptococci and Streptococcus pneumoniae. It also had good to moderate activity against Bacillus spp., Corynebacterium spp., Enterococcus faecalis, and methicillin-resistant staphylococci. Although ciprofloxacin was the most active agent tested against the Enterobacteriaceae, moxifloxacin inhibited the majority of these isolates at < or =2.0 microg/ml. Moxifloxacin was the least active of the three agents tested against Pseudomonas aeruginosa, but had significant activity against other non-fermentative Gram-negative bacilli including Acinetobacter spp., Flavobacterium spp., Pseudomonas spp. other than P. aeruginosa, and Stenotrophomonas maltophilia. The overall broad spectrum of moxifloxacin, and its availability for both oral and parenteral administration, warrants its evaluation for the prevention and treatment of infections in cancer patients.

Anti-Infective Agents↗
PubMed1990

Functional similarity of Listeria ivanovii and Staphylococcus aureus in CAMP test.

On the basis of synergistic haemolysis of Listeria ivanovii and Rhodococcus equi, we suspected CAMP positiveness of R. equi and complete CAMP negativeness of L. ivanovii and confirmed that the latter, showing a double-zone haemolysis like Staphylococcus aureus, could produce the same phenomenon in the CAMP test if used instead of staphylococci. This functional similarity of L. ivanovii and CAMP Staphylococcus could be used as an additional diagnostic test for L. ivanovii.

Hemolysis↗
PubMed2001

Microbial reduction of alpha-chloroketone to alpha-chlorohydrin.

Microbial reduction of alpha-chloroketone to alpha-chlorohydrin was studied as one of the approaches for construction of the chiral center of the corresponding epoxide. About 100 microorganisms covering many species of Candida, Pichia, Hansenula, Geotrichum, Rhodococcus and Aureobasidium were screened to reduce the alpha-chloroketone stereospecifically. Many strains provided the R-alpha-chlorohydrin with 100% enantiomeric excess (ee), e.g., Candida sonorensis SC 16117, Geotrichum candidum SC 5469, Rhodotorula glutinis SC 16293, Sphingomonas paucimobilis SC 16113, Pichia silvicola SC 16159 and Rhodococcus equi SC 15835. Few microorganisms showed preferential formation of S-alpha-chlorohydrin after reduction. Among them, Pichia pinus SC 13864 and two Pichia methanolica strains SC 16116 and SC 13860 were the best, providing the S-alpha-chlorohydrin with ee of 88%, 79% and 78%, respectively. The enantiospecificity of the reduction by these Pichia species can be modified by changing the pH or prior heat treatment of the cells and S-alpha-chlorohydrin with > or =95% ee was obtained by appropriate modification of reaction conditions.

Bacteria↗
PubMed1999

The smcL gene of Listeria ivanovii encodes a sphingomyelinase C that mediates bacterial escape from the phagocytic vacuole.

The ruminant pathogen Listeria ivanovii differs from Listeria monocytogenes in that it causes strong, bizonal haemolysis and a characteristic shovel-shaped co-operative haemolytic ('CAMP-like') reaction with Rhodococcus equi. We cloned the gene responsible for the differential haemolytic properties of L. ivanovii, smcL. It encodes a sphingomyelinase C (SMase) highly similar (> 50% identity) to the SMases from Staphylococcus aureus (beta-toxin), Bacillus cereus and Leptospira interrogans. smcL was transcribed monocistronically and was expressed independently of PrfA. Low-stringency Southern blots demonstrated that, within the genus Listeria, smcL was present only in L. ivanovii. We constructed an smcL knock-out mutant. Its phenotype on blood agar was identical to that of L. monocytogenes (i.e. weak haemolysis and no shovel-shaped CAMP-like reaction with R. equi ). This mutant was less virulent for mice, and its intracellular proliferation was impaired in the bovine epithelial-like cell line MDBK. The role of SmcL in intracellular survival was investigated using an L. monocytogenes mutant lacking the membrane-damaging determinants hly, plcA and plcB, being thus unable to grow intracellularly. Complementation of this mutant with smcL on a plasmid was sufficient to promote bacterial intracellular proliferation in MDBK cells. Transmission electron microscopy showed that SmcL mediates the disruption of the phagocytic vacuole and the release of bacteria into the cytosol. Therefore, L. ivanovii possesses a third phospholipase with membrane-damaging activity that, together with PlcA and PlcB, may act in concert with the pore-forming toxin Hly to mediate efficient escape from the vacuolar compartment. The 5' end of smcL is contiguous with the internalin locus i-inlFE, which is also specific to L. ivanovii and is required for full virulence in mice. Thus, smcL forms part of a novel virulence gene cluster in Listeria that is species specific.

Amino Acid Sequence↗
PubMed2002

Bacterial flora in foals with upper respiratory tract infections in Poland.

Bacteria isolated from nasal cavity of 80 foals with upper respiratory tract infection, as well as from 20 healthy foals, were examined. Within the group of sick animals, from 18 (22.5%) bacteria with recognized pathogenicity were isolated. Coagulase-negative staphylococci and Acinetobacter sp. were the dominant species identified (100 and 45%, respectively). No bacteria species with recognized pathogenicity were isolated from the group of healthy animals. Three cases of death within the group of sick foals were investigated. Rhodococcus equi in two cases and Klebsiella pneumoniae pneumoniae together with Escherichia coli were isolated post-mortem from lung abscesses.

Acinetobacter↗
PubMed2002

Clostridium difficile infections in animals with special reference to the horse. A review.

In human medicine, Clostridium (C.) difficile is since many years a well-known cause of nosocomial diarrhea induced by antibiotic treatment. In horses, C. difficile was recently suggested as a possible enteric pathogen. The bacterium is associated with acute colitis in mature horses following treatment with antibiotics. C. difficile, and/or its cytotoxin, is also associated with acute colitis in mares when their foals are being treated with erythromycin and rifampicin for Rhodococcus equi pneumonia. The colitis can have resulted from an accidental ingestion of erythromycin by the mares. In an experimental study it was also demonstrated in mature horses that erythromycin can induce severe colitis associated with proliferation of C. difficile. A new interesting finding was that in healthy foals younger than 14 days, C. difficile was isolated from every third foal whereas older foals proved negative. In this paper the current state of knowledge of C. difficile infections in animals, especially in horses, is reviewed. A short description is given of the historical background of Clostridium difficile and the antibiotic-associated colitis and diarrhea caused by infection with this bacterium. The taxonomy of Clostridium difficile is described extensively. A summary is given of the diseases associated with clostridia infections in animals. Special attention is paid to the pathogenesis, epidemiology, clinical symptoms, laboratory diagnosis, and pathology of Clostridium difficile infections in horses. Finally, some other bacterial causes of colitis in horses are discussed shortly.

Animals↗
PubMed2003

Isolation and 16S DNA characterization of soil microorganisms from tropical soils capable of utilizing the herbicides hexazinone and tebuthiuron.

Six non-fermentative bacteria were isolated from Colombian (South America) and Hawaiian (USA) soils after enrichment with minimal medium supplemented with two herbicides, hexazinone (Hex) and tebuthiuron (Teb). Microscopic examination and physiological tests were followed by partial 16S DNA sequence analysis, using the first 527 bp of the 16S rRNA gene for bacterial identification. The isolated microorganisms (and in brackets, the herbicide that each degraded) were identified as: from Colombia. Methylobacterium organophilum [Teb], Paenibacillus pabuli [Teb], and Micrmbacterium foliorum [Hex]; and from Hawaii, Methylobacterium radiotolerans [Teb], Paenibacillus illinoisensis [Hex], and Rhodococcus equi [Hex]. The findings further explain how these herbicides, which have potential for illicit coca (Erythroxylum sp.) control, dissipate following their application to tropical soils.

Bacteria↗
PubMed1994

Animal-associated opportunistic infections among persons infected with the human immunodeficiency virus.

A number of animal-associated infections occur in persons infected with the human immunodeficiency virus (HIV), including those due to Toxoplasma gondii, Cryptosporidium, Microsporida, Salmonella, Campylo-bacter, Giardia, Rhodococcus equi, Rochalimaea, and Listeria monocytogenes. Most of these infections, with the exception of those due to Rochalimaea, appear to be acquired by the immunosuppressed individual from sources other than exposure to animals. Drs. Glaser and colleagues review our current understanding of the role of exposure to animals, especially pets, in the natural history of these opportunistic infections. They suggest that the risk of zoonotic transmission is small and offer practical suggestions designed to reduce this low risk. They conclude that the benefits of animal companionship outweigh the risks to patients and that prohibition of pet ownership by individuals infected with HIV is not warranted.

AIDS-Related Opportunistic Infections↗
PubMed1996

Cavitary pulmonary lesions in patients infected with human immunodeficiency virus.

The differential diagnosis of cavitary pulmonary lesions in individuals infected with human immunodeficiency virus (HIV) is broad, especially in patients with advanced disease. In patients with Pneumocystis carinii pneumonia, cavitation is an uncommon manifestation of a common disease. It is unusual in patients with pulmonary cryptococcosis, coccidioidomycosis, and histoplasmosis but occurs frequently in patients with invasive pulmonary aspergillosis. In patients with pulmonary tuberculosis, cavities are more common during earlier stages of HIV disease, when cellular immunity is relatively preserved. Mycobacterium avium complex is an uncommon cause of lung disease and infrequently produces cavities. However, Mycobacterium kansasii, is often associated with cavitation. Cavities can complicate any bacterial pneumonia and are especially common with pneumonia due to Pseudomonas aeruginosa, Nocardia asteroides, and Rhodococcus equi. Noninfectious causes of cavitary lesions are rare, but cavitary lesions caused by pulmonary Kaposi's sarcoma and non-Hodgkin's lymphoma have been reported. Because of the broad differential diagnosis and because most cavities are caused by treatable opportunistic infections, a definitive diagnosis is essential.

AIDS-Related Opportunistic Infections↗
PubMed1989

Activity of meropenem, against gram-positive bacteria.

A new carbapenem antibiotic, meropenem, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative, methicillin-susceptible staphylococci equally well. Among the comparative antimicrobials examined, only N-formimidoyl-thienamycin (imipenem) was two to four times more active than meropenem. Compared with vancomycin or methicillin, meropenem was 10-20 times more active. Strains of 11 species of streptococci were highly susceptible to meropenem; the geometric mean MICs of the drug for these species ranged from 0.01 to 0.04 mg/l. The agent, however, only had moderate activity against Enterococcus faecalis (mean MIC 5 mg/l) and Ent. faecium (mean MIC 11.6 mg/l). Among Corynebacterium jeikeium, strains were encountered that showed susceptibility to meropenem but resistance to imipenem and other beta-lactams. Strains of other corynebacteria, Rhodococcus equi, Erysopelothrix rhusiopathiae, Listeria monocytogenes, and Bacillus spp. all were highly susceptible to meropenem (mean MICs 0.04-0.17 mg/l). Although methicillin-resistant staphylococci were inhibited by concentrations of 1-2 mg/l of meropenem in agar dilution tests, such strains showed heteroresistance in population studies, as is typical for all beta-lactam antibiotics. In addition, the biochemical correlate of methicillin-resistance, penicillin-binding protein 2', showed low affinity for meropenem, similar to that for imipenem. Meropenem was as bactericidal as imipenem and comparative bactericidal antimicrobials in killing-curve experiments. Strains of Ent. faecium, C. jeikeium, and L. monocytogenes were killed at a slower rate than streptococci or staphylococci.

Bacterial Proteins↗
PubMed1999

The bactericidal activities of HMR 3004, HMR 3647 and erythromycin against gram-positive bacilli and development of resistance.

The bactericidal activities of two new ketolides, HMR 3004 and HMR 3647, and the potential to develop resistance to these two antibiotics were studied in Gram-positive bacilli. As judged by time-kill kinetics both ketolides were mostly bacteriostatic, being bactericidal against only highly susceptible isolates of Corynebacterium striatum (two isolates) and Corynebacterium minutissimum (one isolate). Spontaneous resistant mutants were detected in seven of 30 strains tested, mainly in Rhodococcus equi, C. minutissimum and C. striatum, with a very low frequency of mutation (10(-12)-10(-15)).

Animals↗
PubMed1996

Community-acquired bacteremia in human immunodeficiency virus-infected children in Harare, Zimbabwe.

BACKGROUND: HIV infection is common in mothers and their children in Zimbabwe, and HIV-infected children are particularly susceptible to bacterial infections. There is little information on the etiology and outcome of HIV-related bacteremia in African children. METHODS: Blood cultures from 309 hospitalized children in Zimbabwe, of whom 168 were diagnosed as having HIV, were examined for pathogens. The association among significant bacteremia, HIV infection and mortality was assessed in these children. RESULTS: The most common isolates were coagulase-negative staphylococci (31 children, 25 clinically significant), Staphylococcus aureus (22 children) and Streptococcus pneumoniae (20 children). Nontyphoidal Salmonella (10 children), Escherichia coli (4 children) and Klebsiella sp. (4 children) were the most frequent Gram-negative bacteria. Two children had Rhodococcus equi pneumonia. HIV-infected children showed increased risk of bacteremia (odds ratio (OR) = 2.68), especially if younger than 18 months of age (OR = 2.94), and high risk of enterobacteremia (OR = 15.76). There was no significant association of bacteremia with nutritional status. Mortality was 17% overall but was higher in HIV-infected children up to 6 months of age (OR = 2.81) and in bacteremic children of any age (OR = 2.03). CONCLUSIONS: Prompt recognition of pathogens and early administration of appropriate antimicrobials is important in reducing the morbidity and mortality associated with bacteremia in HIV-infected children in Africa.

AIDS-Related Opportunistic Infections↗