[Therapy of staphylococcus infections].
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As a rule, coagulase-negative staphylococcal infections in the neonate is an acquired iatrogenic infection. It usually occurs in premature infants with an in-dwelling catheter. Clinical and laboratory criteria are used to differentiate contaminated samplings from true infection. the frequency of methicillin-resistant strains justifies the use of vancomycin combined with an aminoglycoside and, in the first days, with rifampicin, all drugs administered in doses calculated for the post-conception age. This treatment is also administered in mother-to-foetus infections caused by CNS.
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An epizootic of Staphylococcus infection causing abscesses was encountered in a small-scale breeding colony of nude mice of BALB/c background. The incidence of abscess was sporadic and mostly nude (nu/nu) mice aged over 3 months were affected. Staphylococcus aureus was isolated from the face, oral cavity, and feces of almost all nu/nu and heterozygous (nu/+) mice in the colony. After a prolonged time period, up to 10 to 14 months of age, almost all the S. aureus-carrying nu/nu mice produced abscesses and eventually died. Athymicity of the host seemed to be a prerequisite for the abscess formation since nu/+ mice were spared from the lesions. Also, transfer of immunocompetent spleen cells cured the abscesses of the affected nude mice.
The susceptibility of uninfected or Staphylococcus chromogenes-infected quarters to challenge with Staphylococcus aureus was measured. Seventeen S. chromogenes-infected quarters were challenged by infusion of S. aureus into the teat sinus; 47% (8 of 17) became infected and all 18 uninfected quarters challenged similarly with S. aureus became infected. No differences in daily milk yield were seen between uninfected quarters and S. chromogenes-infected quarters prior to S. aureus infusion. Postinfusion, milk yield for S. aureus-infected, S. chromogenes-infected, and S. chromogenes- and S. aureus-infected quarters differed. Somatic cell counts were elevated in S. chromogenes-infected quarters compared with uninfected quarters prior to S. aureus infusion. Somatic cell counts were not different between S. aureus- and S. chromogenes- and S. aureus-infected quarters postinfusion, but were different for S. chromogenes-infected quarters. Chloride concentrations in S. chromogenes- and S. aureus-infected quarters were different from either S. aureus-infected or S. chromogenes-infected quarters. Staphylococcus aureus colony forming units in quarters with preexisting S. chromogenes infections were lower than S. aureus colony-forming units in previously uninfected quarters. Possible protective mechanisms induced by S. chromogenes against superinfection by S. aureus are discussed.
Staphylococcus aureus infections are often life threatening. Relatively little is known about the host response to these infections, in particular, the role played by cytokines. We established a mouse model of bacteremic S. aureus infection to correlate bacteriologic findings and pathologic changes with cytokine gene expression. Bacterial density in blood and tissue was highest at 1 h and minimal by 48 h. Despite the rapid clearance of bacteria, pathologic abnormalities and inflammatory cytokines were detected after clearance of the bacteria. The number of infiltrating inflammatory cells, as well as the size of inflammatory foci, increased with time. Interstitial accumulation of inflammatory cells and tissue damage, such as microabscesses, edema, and necrosis progressed following clearance of bacteria from the tissues. Levels of tumor necrosis factor and interleukin-1 protein in serum were detectable at 1 h and peaked at 4 h. Interleukin-6 protein expression showed different kinetics, with low levels detected at 1 h and increasing levels at 72 h postinfection. Tumor necrosis factor and the interleukins were expressed in inflammatory and noninflammatory cells in lung, liver, and heart tissues. Leukocytes in the infected tissues were highly reactive with antibodies to the three cytokines, suggesting that activated leukocytes are a major source of inflammatory cytokines after staphylococcal infection. Expression of interleukin-1 and interleukin-6 in tissue-specific cells and endothelial cells was also detected in infected tissues, indicating that cells other than leukocytes contribute to the elevated cytokine levels in this model. Once initiated, expression of inflammatory cytokines contributes to the pathogenesis of S. aureus disease.
An increased extracellular production of free radicals with bactericidal activity does not improve the efficacy of intracellular digestion of Staphylococci. The amount of intracellular oxygen reactive species generated by the neutrophils from patients with an infectious condition has been found considerably decreased as compared to healthy donors. On the other hand, the excess of secretion of free radicals into the extracellular space leads inevitably to the adaptive increase of antioxidant enzymes and, as a result, to an increase in the total antioxidant capacity of the blood plasma. Indeed, patients with septicemia at its highest peak (at the moment of hospitalization) showed a significant increase (more than twice) in the parameters of catalase and superoxide dismutase activity; the antioxidant capacity of the plasma was elevated as well. The patients of the other two groups in our study (with a localized infection) did not show any statistically significant rise in these parameters. On the second day after the initiation of an intensive treatment the activity of the enzymes and the total antioxidant capacity of the plasma dropped sharply below the normal level. Therefore, the staphylococcus infection, especially its generalized from, is characterized by an increased extracellular secretion of radicals together with a decreased generation of intracellular radicals. On one hand this leads to the failure of the intracellular killing, on the other--to the inflammatory free radical-mediated damage of the host cells and tissues. Cytokines, such as interleukins and interferons, can regulate the free radical-mediated processes during the staphylococcus infections. The effect of the two recombinant cytokines (IL-1 beta, IFN-gamma) on the character of free radical production and intracellular killing of Staphylococci by neutrophils isolated from the blood of patients and healthy donors has been studied. The analysis of the effect of cytokines on the radical production by phagocytes revealed a redistribution of the extracellular and intracellular fractions of free radicals rather than a general increase of the oxygen active metabolite production. As expected, the increment in the number of intracellular radicals improved significantly the process of phagocytosis.
The synthesis of viral and host DNA in phage-infected Staphylococcus aureus was examined. Three intracellular forms of phage 52HJD DNA were demonstrated: covalently closed circular, open circular, and linear DNA species. It was noted that infection of S. aureus-propagating strains 81 and 52 with phage 52HJD inhibited the replication of the bacterial chromosome and a stringently controlled penicillinase plasmid. A small tetracycline plasmid, normally under relaxed replication control, continued to replicate in the postinfection period. No breakdown of the host chromosome into small-molecular-weight fragments or utilization of bacterial DNA material for the synthesis of viral DNA was observed.
The reactions of periventricular tissue of the lateral ventricle to non-infected and infected (Staphylococcus Epidermidis) silicone shunt tubing were examined by light and transmission electron microscopy. It was shown that reactive changes occurred in periventricular tissue in response to the implant of sterile shunt tubing. On the other hand in infected implanted silicone shunt tubing, proliferation of inflammatory cells within the ventricle and periventricular tissue, loss of integrity of the ependyma, glial cell proliferation, and excessive extracellular oedema were demonstrated. Proliferation of ependymal cells combined with inflammatory responses may be a factor in the pathogenesis of infected shunt obstruction.
Experiments carried out on 134 newborn mice showed that influenza virus and staphylococcus infection and their combination induces local necrosis in the myocardium. Morphometric measurement has shown that the extent of necrotic changes amounted with the action of the influenza virus to 1.37%, with the action of staphylococcus to 1.4% and with their combined action to 1.8%. Electron microscopy revealed dystrophic changes in cardiomyocytes with subsequent intracellular regeneration.
Implant-associated infections offer resistance to antibiotic treatment and possibly do so because the causative bacteria which reside on the artificial surface are enclosed in a protective matrix (biofilm) shielding the bacteria against the action of host defenses and antibiotic action. We have investigated in vitro the effect of various antimicrobial agents on biofilms of Staphylococcus epidermidis, which is the main organism responsible for implant-associated infections. Rifampin was found to exert superior activity, albeit incomplete, against S. epidermidis biofilms using an assay system which enabled the determination of the kinetics of antibiotic action over five days. In a large screening study looking for agents capable of completing the action of rifampin, gentamicin was unexpectedly found to be antagonistic to rifampin. The present study was undertaken to investigate further the activity of gentamicin and five other aminoglycoside antibiotics using a wider range of concentrations (2.5-20 micrograms/mL). The main findings were a marked synergy with rifampin demonstrated by streptomycin, producing a bactericidal outcome, which contrasted sharply with the indifference or antagonism shown by the other aminoglycosides. We then studied in further detail the effect of separate combinations of streptomycin and gentamicin with rifampin over a wider concentration range of each agent (1.25-40 micrograms/mL). Streptomycin showed strong rapid synergy with rifampin even at the lowest concentration of each antibiotic. Gentamicin demonstrated a concentration-related antagonism towards rifampin which was independent of rifampin concentration. The data support the conclusion that streptomycin, like cell-wall active antibiotics, exerts a potent synergy with rifampin against S. epidermidis biofilms, and that the other aminoglycosides, predominantly gentamicin, strongly antagonize rifampin action.(ABSTRACT TRUNCATED AT 250 WORDS)
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Staphylococcus aureus is a frequent cause of infections in both the community and hospital. Worldwide, the increasing resistance of this pathogen to various antibiotics complicates treatment of S aureus infections. Effective measures to prevent S aureus infections are therefore urgently needed. It has been shown that nasal carriers of S aureus have an increased risk of acquiring an infection with this pathogen. The nose is the main ecological niche where S aureus resides in human beings, but the determinants of the carrier state are incompletely understood. Eradication of S aureus from nasal carriers prevents infection in specific patient categories-eg, haemodialysis and general surgery patients. However, recent randomised clinical trials in orthopaedic and non-surgical patients failed to show the efficacy of eliminating S aureus from the nose to prevent subsequent infection. Thus we must elucidate the mechanisms behind S aureus nasal carriage and infection to be able to develop new preventive strategies. We present an overview of the current knowledge of the determinants (both human and bacterial) and risks of S aureus nasal carriage. Studies on the population dynamics of S aureus are also summarised.
Staphylococcus aureus is a major pathogen in bovine intramammary infections of subclinical and chronic nature. Persistent infection with S. aureus has been postulated to be associated with an impaired immune response. This study was designed to define changes in peripheral blood and milk cell subpopulations during chronic S. aureus infection. The expression of specific antigens on the surface of lymphocytes and neutrophils was studied by flow cytometry. Cytokines and cytokine transcripts elaborated by the milk-derived cells were also investigated, using ELISA and reverse transcription polymerase chain reaction, respectively. The results indicated that cell subpopulations in blood from infected cows were not modified. In contrast, changes occurred in infected milk: neutrophils were the main cell population, but they were not in a highly activated state; the CD8+ T-lymphocytes were mainly recruited compared with the CD4+ T-lymphocytes, suggesting that CD8+ T-lymphocytes play an important role in chronic S. aureus infection. Also, the proportion of the B-lymphocytes among the total lymphocyte population was increased, suggesting that a humoral response developed, and no change was observed in the gammadelta subset. No cytokine mRNA was found in milk cells from uninfected mammary glands. In contrast, interleukin (IL)-1alpha, IL-1beta, IL-6 and tumor necrosis factor alpha pro-inflammatory cytokine and IL-10 and IL-12 regulatory cytokine mRNA were synthesized in cells derived from infected mammary glands, whereas no IL-2 nor IL-4 mRNA were found. Therefore, cells present in milk during chronic S. aureus infection were activated, but did not reveal any polarization of the immune response.
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