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Primary infection with zidovudine-resistant human immunodeficiency virus type 1 does not adversely affect outcome at 1 year. Sydney Primary HIV Infection Study Group.

Human immunodeficiency virus type 1 (HIV-1) variants with reduced in vitro sensitivity to zidovudine, conferred by specific mutations in the viral reverse transcriptase, emerge during prolonged therapy. Late-stage disease and declining CD4 cell count are associated with more rapid emergence of these resistant variants. Isolates of HIV-1 from seroconverters were screened for the zidovudine-resistance marker mutation at codon 215. HIV-1 with the altered genotype was detected in 5 (8.2%) of 61 patients soon after onset of symptomatic primary illness and from the sex partner of 1 patient. These transmitted resistant viruses were either replaced by strains susceptible to zidovudine within a few months of infection or persisted for up to 1 year in the absence of prolonged zidovudine therapy. The resistant genotype persisted in 3 of 5 seroconverters but in 2 patients had reverted to wild type at 48 and 52 weeks. Primary infection with zidovudine-resistant variants of HIV-1 was not associated with a more severe symptomatic primary illness or more rapid CD4 cell decline at 1 year after infection.

Acquired Immunodeficiency Syndrome↗

The efficacy of honey in inhibiting strains of Pseudomonas aeruginosa from infected burns.

Because there is no ideal therapy for burns infected with Pseudomonas aeruginosa, there is sufficient need to investigate the efficacy of alternative antipseudomonal interventions. Honey is an ancient wound remedy for which there is modern evidence of efficacy in the treatment of burn wounds, but limited evidence for the effectiveness of its antibacterial activity against Pseudomonas. We tested the sensitivity of 17 strains of P. aeruginosa isolated from infected burns to two honeys with different types of antibacterial activity, a pasture honey and a manuka honey, both with median levels of activity. All strains showed similar sensitivity to honey with minimum inhibitory concentrations below 10% (vol/vol); both honeys maintained bactericidal activity when diluted more than 10-fold. Honey with proven antibacterial activity has the potential to be an effective treatment option for burns infected or at risk of infection with P. aeruginosa.

Anti-Bacterial Agents↗

Fungal colonisation and fluconazole therapy in acute liver disease.

BACKGROUND/AIMS: Fungal infection, particularly with Candida spp., has been identified as an important cause of morbidity and mortality in patients with acute liver failure. Fungal colonisation of superficial mucosal sites usually precedes invasive infection. We investigated colonisation patterns in patients with acute liver disease receiving fluconazole therapy in order to investigate the possibility of emergence of fluconazole-resistant C. albicans or other species. METHODS: During a 6-month study period, we studied all patients referred to our unit with acute liver disease by twice-weekly sampling and mycological analysis of specimens from superficial mucosal and other sites as appropriate. Patients were treated with prophylactic antimicrobials including 100 mg fluconazole daily in accordance with our usual protocol. RESULTS: Twenty-two patients with acute liver disease were studied, eight of whom underwent transplantation. Eighteen patients were colonised by fungi at presentation, and six developed secondary colonisation during fluconazole therapy. Four of these patients (all transplanted) became colonised by resistant species; one of these was Aspergillus fumigatus, which led to death. There were no other invasive fungal infections identified during the study period, and no fluconazole-resistant C. albicans were identified. CONCLUSIONS: Resistance to fluconazole is unlikely to develop in C. albicans during short-term fluconazole prophylaxis in acute liver disease, and in this study we did not find evidence of invasive disease from other Candida spp. during fluconazole therapy. However, in patients at particularly high risk, other strategies are required to prevent infection with Aspergillus spp.

Antifungal Agents↗

Selection of strains for quality assessment of the disk induction method for detection of inducible clindamycin resistance in Staphylococci: a CLSI collaborative study.

A nine-laboratory collaborative study was conducted to select positive and negative quality assessment control strains for the detection of inducible clindamycin resistance in staphylococci. Four strains of Staphylococcus aureus were tested as unknowns on 10 different days in each laboratory using the recently recommended CLSI (formerly NCCLS) disk diffusion method and the inoculum purity control method. Strains contained either macrolide-lincosamide-streptogramin B (MLSB) resistance genes encoded by erm(A) or erm(C) or a macrolide resistance efflux pump encoded by msr(A). Based upon the results of this study, strain UT 32 (now designated ATCC strain BAA-977) containing erm(A) is recommended as the positive control organism for inducible clindamycin resistance. Strain UT 25 (now designated ATCC BAA-976), which harbors the efflux pump encoded by msr(A), is recommended as the negative control organism.

Anti-Bacterial Agents↗

Increased diuron resistance in the joint expression of mutations located at the DIU2, DIU3 and DIU4 loci of Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, diuron blocks the respiratory pathway at the level of the bc1 complex. Two mitochondrially inherited loci, DIU1 and DIU2, located in the cytochrome b gene, and two nuclearly inherited loci, DIU3 and DIU4, have previously been identified. The present work genetically characterizes two double mutants. One mutant, Diu-217, carries two nuclearly inherited mutations, diu3-217a and diu-217b; the second mutant, Diu-783, carries the previously described nuclear mutation diu3-783 and a mitochondrial mutation diu2-783. Each mutation, independent of its location, exhibits a weak diuron resistance. The joint expression of two or three mutations leads to a cumulative or a cooperative enhanced diuron-resistant phenotype.

Alleles↗

Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.

Experimentally induced murine graft-vs.-host disease may be characterized by hypergammaglobulinemia, autoantibody formation, and immune complex-mediated organ system damage that mimics SLE. These autoimmune phenomena are mediated by abnormal Th-B cell cooperation, across MHC disparities, in which donor-derived allospecific Th cells recognize and interact with MHC class II antigens on the surface of recipient B cells. Microbial toxins, termed superantigens, which bind to MHC class II molecules and activate selected T cells based on TCR variable gene usage, may induce a similar form of Th-B cell interaction. In the present study, we generated and characterized human Th cell lines reactive with the Mycoplasma arthritidis superantigen (MAM). The essential observation is that resting human B cells bind MAM and present it to superantigen-reactive autologous or allogeneic Th cells, resulting in both Th cell activation and a consequent polyclonal Ig response by the superantigen-bearing B cells.

Antigens↗

Anti-Candida activity of calprotectin in combination with neutrophils or lactoferrin.

The effect of an anti-microbial protein, calprotectin, in combination with neutrophils on the growth of Candida albicans was investigated. The growth inhibition of C. albicans by murine neutrophils was augmented by the addition of a low concentration of calprotectin prepared from rat peritoneal exudate cells. The concentrations of calprotectin causing 50% inhibition of growth of C. albicans in the absence or presence of neutrophils at an effector-to-target (E/T) ratio of 30 and 60 were estimated to be 0.45, 0.34 and 0.28 U/ml, respectively. The anti-Candida activity of calprotectin was completely inhibited by 2 microM of zinc ion, while it only partially lowered the activity of the combination of calprotectin and neutrophils. Lactoferrin, which is an anti-microbial protein released from neutrophils, strongly inhibited the growth of C. albicans in combination with calprotectin. These results suggest that calprotectin and lactoferrin released from neutrophils may cooperate to inhibit the growth of C. albicans at a local lesion of the infection where there is an accumulation of neutrophils.

Animals↗

Periodontal infections and cardiovascular disease--how strong is the association?

In the past decade there has been renewed interest in the old hypothesis that infections increase the risk of developing cardiovascular disease and stroke. There is now a convincing body of evidence that atherosclerosis has a major inflammatory component and is much more than the simple vascular accumulation of lipids. Infectious agents that have been linked to an increased risk of coronary heart disease (CHD) include Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesviruses. The concept has emerged that each of these agents is an independent risk factor for CHD and that common chronic infections are important. In addition, periodontal infections have also been implicated as one of several factors contributing to the development of CHD. Evidence supporting a causative role of chronic infections in CHD is largely circumstantial. However, the evidence is sufficiently strong to warrant further examination of the possible link between chronic infections and CHD. In this review the lines of evidence for a causative role of C. pneumoniae in the development of CHD are summarized and contrasted with the lines of evidence suggesting a periodontal infection--CHD association. If common or widespread chronic infections are truly important risk factors for CHD, it is unlikely that a single infection will be shown to be causative. It is likely that the entire microbial burden of the patient from several simultaneous chronic infections is more important (e.g., H. pylori-caused gastric ulcers + C. pneumoniae-caused bronchitis + periodontitis). Increased cooperation between cardiologists and periodontists will be required to determine if, and what, combinations of common chronic infections are important in the pathogenesis of CHD and stroke.

Arteriosclerosis↗

Process of infection with bacteriophage phi-X174. XXXIV. Kinetic of the attachment and eclipse steps of the infection.

The products of phiX cistrons II, III, and VII are demonstrated to affect the attachment of the phage to its host Escherichia coli C; therefore, by inference, these cistrons influence, directly or indirectly, the structure of proteins in the virus particle. Two of the mutations which alter attachment kinetics, ts79 in cistron III and h in cistron VII, also affect the electrophoretic mobility of the virus and emphasize the role of charge in the attachment interaction with the host. The kinetics for attached phage to go into "eclipse" are first-order and biphasic; about 85% of the phage eclipse at one rate (k(e) = 0.86 min(-1)) and the remainder do so at a distinctly lower rate (k(e) = 0.21 min(-1)). No phiX cistrons yet identified affect the eclipse process. The lowest temperature at which eclipse is detected is 19 C. The Arrhenius activation energy for phage eclipse has the high value of 36.6 kcal/mole, indicating the cooperative nature of the event.

Coliphages↗

Correlation between microbial enzyme activities in the rumen fluid of sheep under different treatments.

Five total mixed rations prepared from finger millet (Eleusine Coracana) straw as a roughage (48%) and mixed concentrate (52%), supplemented with a 1% isoacid mixture (i-C4, i-C5, C5 and phenylacetic acid in equal proportions) or oil (groundnut oil, 5% more than the control) or urea (5% more nitrogen than the control), and protein (groundnut cake, 5% more nitrogen than the control) were given in a Latin square experiment to sheep. Enzymatic activities were estimated for urease, cellulase, protease, amylase, and lipase in various fractions of rumen fluid on the one hand and rumen microbial biomass on the other hand. Rumen samples were taken 3-4 hours after feeding and mixed rumen bacteria were separated as a strained rumen fluid without protozoa (SRFWP), cell free rumen fluid (CFRF) and enzymes associated with the bacteria cell (EABC). Samples of SRFWP and EABC contained higher enzyme activities than CFRF. Depending on the type of enzymes in each fraction, some significant coefficient of determination (r2) was seen. These values showed very close cooperative action between proteolytic and amylolytic enzymes under the experimental conditions, or perhaps the presence of some species of bacteria with both activities. Lipolytic bacteria are completely specialized for lipase production only (P < 0.05). The results showed oil, isoacid and crude protein enhanced microbial production (P < 0.05) and this can change the pattern of enzymes in the rumen of sheep.

Amylases↗

A low-morbidity murine model of peritonitis.

PURPOSE: Peritonitis continues to be a major source of mortality and morbidity in patients undergoing abdominal surgery. The aim of this study was to develop a nonfatal model of bacterial peritonitis in mice so that we could study aspects of the pathobiology and treatment of peritonitis in an in vivo model. METHODS: Mice were inoculated via a midline laparotomy with 0.5 mg of zymosan in 0.1 ml of saline into the subomental space. At 24, 48, and 96 hours after treatment, animals were killed, and analysis was performed to determine the degree of peritoneal inflammation. End points included intraperitoneal cellular influx, tumor necrosis factor-alpha concentrations, and myeloperoxidase activity. In addition, peritoneal lavage fluid was plated onto blood agar for analysis of bacterial colony-forming units. There were 40 mice in each group. RESULTS: There were no deaths in either group. Facultative Gram-negative bacteria were cultured from the peritoneal cavities of zymosan-treated animals at 24 and 48 hours after insult (colony-forming unit counts of 92+/-11 vs. 0 in control animals). In the zymosan-treated animals, there were significantly increased numbers of inflammatory cells (especially neutrophils) in the peritoneal cavity at 24 and 48 hours after treatment; these numbers returned to control levels by 96 hours. Myeloperoxidase activity was also elevated both in the peritoneal fluid (2.4 X 10(-4) units/ml compared with 1.6 x 10(-4) units/ml, P < 0.05) and in remote organs (i.e., lung, P < 0.05; liver, P < 0.001; and kidney, P < 0.05) at 24 hours after treatment. There was no significant difference in tumor necrosis factor-alpha levels between zymosan-treated and control mice in either serum or peritoneal fluid at any time point investigated. There was no mortality in either the zymosan-treated or control animals. CONCLUSION: In this model of bacterial peritonitis in mice, we have demonstrated how the peritoneal cavity can resolve a relatively localized inflammatory insult within 96 hours of induction. This response is characterized by a cellular influx of predominantly neutrophils and macrophages and by pronounced oxidative activity. We will use this in vivo model to characterize aspects of the pathobiology and treatment of peritonitis.

Animals↗

Efficacy of vancomycin and teicoplanin alone and in combination with streptomycin in experimental, low-level vancomycin-resistant, VanB-type Enterococcus faecalis endocarditis.

The efficacy of vancomycin (VM) and teicoplanin (TE), alone and in combination with streptomycin (SM), against enterococci that express low-level VanB-type VM resistance was investigated in experimental endocarditis using isogenic strains of Enterococcus faecalis susceptible to glycopeptides and aminoglycosides or inducibly resistant to low levels of VM (MIC = 16 micrograms/ml). VM was significantly less active against the resistant strain than against the susceptible strain, establishing that low-level VanB-type VM resistance can influence therapeutic efficacy. By contrast, TE had equally good activity against both strains. VM or TE combined with SM was synergistic and bactericidal against the resistant strain in vitro. While both combinations were efficient in reducing bacterial density in vivo, TE plus SM was significantly superior to VM plus SM if valve sterilization was considered. These data suggest that despite the presence of low-level VanB-type resistance, combination therapy with a glycopeptide and SM (and presumably other aminoglycosides to which there is not high-level resistance) will nevertheless provide effective bactericidal activity.

Animals↗

In vitro evaluation of voriconazole against some clinically important fungi.

Voriconazole was compared to amphotericin B, fluconazole, and itraconazole by using an in vitro macrobroth dilution test based upon current National Committee for Clinical Laboratory Standards tentative standards against the dimorphic fungi and several opportunistic molds and yeasts. In all instances, the voriconazole MICs were lower than those of fluconazole. In most instances, the MICs were lower than the recorded MICs of amphotericin B and itraconazole.

Antifungal Agents↗

Quality control guidelines for National Committee for Clinical Laboratory Standards recommended broth macrodilution testing of amphotericin B, fluconazole, and flucytosine.

Amphotericin B, fluconazole, and flucytosine (5FC) were tested in a multilaboratory study to establish quality control (QC) guidelines for yeast antifungal susceptibility testing. Ten candidate QC strains were tested in accordance with National Committee for Clinical Laboratory Standards M27-P guidelines against the three antifungal agents in each of six laboratories. Each laboratory was assigned a unique lot of RPMI 1640 broth medium as well as a lot of RPMI 1640 common to all of the laboratories. The candidate QC strains were tested 20 times each against the three antifungal agents in both unique and common lots of RPMI 1640. A minimum of 220 MICs per drug per organism were generated during the study. Overall, 95% of the MICs of amphotericin B, fluconazole, and 5FC fell within the desired 3 log2-dilution range (mode +/- 1 log2 dilution). Excellent performance with all three drugs was observed for Candida parapsilosis ATCC 22019 and C. krusei ATCC 6258. With these strains, on-scale 3 log2-dilution ranges encompassing 96 to 99% of the MICs of all three drugs were established. These two strains are recommended for QC testing of amphotericin B, fluconazole, and 5FC. Reference ranges were also established for an additional four strains for use in method development and for training. Four strains failed to perform adequately for recommendation as either QC or reference strains.

Amphotericin B↗