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PubMed2005

Epidemiology, treatment, and prevention of community-acquired methicillin-resistant Staphylococcus aureus infections.

Since first described In 1961, methicillin-resistant Staphylococcus aureus (MRSA) has become a common nosocomial pathogen. Substantial increases in MRSA infections among nonhospitalized patients are being reported. Methicillin-resistant S. aureus is the most common isolate from skin and soft tissue infections in selected centers in the United States. Community-acquired MRSA strains differ from nosocomial strains in clinically relevant ways, such as in their propensity to cause skin and soft tissue infection and severe necrotizing pneumonia. Clinicians in numerous specialties, particularly primary care physicians, will likely evaluate patients presentIng with community-acquired MRSA and should become familiar with the epidemiology and clinical characteristics of and evolving therapeutic and preventive strategies for this infection.

Community-Acquired Infections↗
PubMed1988

Toxic shock syndrome from Staphylococcus aureus infection at insulin pump infusion sites. Report of two cases.

Two young diabetic females using insulin infusion pump therapy became ill with toxic shock syndrome secondary to Staphylococcus aureus infection at the insulin infusion pump site. Physicians need to be aware of this potential complication in diabetic patients using insulin infusion pump therapy so proper management can be initiated early. Infections at insulin infusion sites are common. Patients need to be instructed in the importance of preventing infections at the pump infusion site and proper management of any abscesses that should develop. Controlled studies evaluating proper management of insulin infusion pump sites to prevent infections are needed.

Abscess↗
PubMed1997

[Severe methicillin-resistant Staphylococcus aureus infections. Emergence of resistance to fusidic acid or fosfomycin during treatment with continuous infusion of vancomycin].

OBJECTIVES: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and to assess the relationship with serum levels of vancomycin METHODS: A retrospective study was performed in patients hospitalized in our intensive care unit during a 3-year period (1993-1995) who were treated for severe MRSA infection with continuous infusion vacomycin and fosfomycin or fucidic acid. We analyzed the development of resistance and serum levels of vancomycin. RESULTS: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomycin developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 micrograms/ml vs. 22.64 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 +/- 1.07 micrograms/ml vs. 21.85 +/- 0.78 microgram/ml, p < 0.01). CONCLUSIONS: Our findings confirm that in spite of continuous vancomycin infusion at an initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfomycin or fucidic acid an develop during ongoing treatment. Vancomycin levels of at least 20 micrograms/ml should be obtained as rapidly as possible.

Anti-Bacterial Agents↗
PubMed2002

Critical role of signaling through IL-1 receptor for development of arthritis and sepsis during Staphylococcus aureus infection.

IL-1R-deficient mice (IL-1R(-/-)) and their wild-type controls (IL-1R(+/+)) were i.v. inoculated with 1 x 10(7) or 10(6) Staphylococcus aureus per mouse to mimic bacterial sepsis and septic arthritis. The disease outcome was severely worsened in the IL-1R(-/-) mice as compared with IL-1R(+/+) mice. Indeed, 3 days after inoculation of 10(7) S. aureus per mouse 84% of IL-1R(-/-) mice displayed clinical signs of septicemia as compared with none of the IL-1R(+/+) mice. On day 9 after inoculation with 10(6) S. aureus per mouse 75% of the IL-1R(-/-) mice were dead as compared with none of the IL-1R(+/+) mice. Also, the number of staphylococci in circulation was 25- to 30-fold increased in IL-1R(-/-) mice as compared with IL-1R(+/+) mice, the most probable reason for the outcome. The frequency and severity of septic arthritis were significantly increased in IL-1R(-/-) mice, as compared with IL-1R(+/+) mice, following i.v. inoculation of staphylococci. This was probably due to an increased accumulation of bacteria in the joints of IL-1R(-/-) mice as compared with their wild-type controls. Interestingly, while serum levels of IL-18 in IL-1R(-/-) mice were significantly lower than in IL-1R(+/+) mice 24 h after inoculation of S. aureus, both IL-18 and IL-1beta were significantly increased in IL-1R(-/-) vs IL-1R(+/+) mice 4 days after the bacterial inoculation. In conclusion, IL-1R signaling plays a crucial role in host protection during systemic S. aureus infection as seen by the fatal outcome of S. aureus sepsis and arthritis in IL-1R-deficient mice.

Animals↗
PubMed2005

Staphylococcus aureus infection of epidermal keratinocytes promotes expression of innate antimicrobial peptides.

Keratinocytes upregulate expression of endogenous antimicrobial peptides in response to inflammatory stimuli. We show that both viable and heat-inactivated Staphylococcus aureus and lipoteichoic acid differentially alter expression of these peptides upon contact with human keratinocytes. The findings indicate a diversity of staphylococcal factors involved in upregulation of antimicrobial peptide expression in cutaneous epithelia.

Antimicrobial Cationic Peptides↗
PubMed1999

A patient who survived total colonic type ulcerative colitis complicated by toxic megacolon, disseminated intravascular coagulation, methicillin-resistant Staphylococcus aureus infection and bilateral femoral phlebothrombosis.

We report a patient who survived total colonic type ulcerative colitis (UC) complicated by toxic megacolon (TM), disseminated intravascular coagulation (DIC), methicillin-resistant Staphylococcus aureus infection, and phlebothrombosis. A 69-year-old man was treated for about 4 months under the diagnosis of ischemic colitis at another hospital, and was transferred to our hospital. Based on endoscopic and pathological findings, we strongly suspected UC, and administered salazosulfapyridine and methylprednisolone, but TM and DIC developed, necessitating urgent subtotal colectomy. Despite his elderly age and the severe complications, he recovered and was discharged from our hospital about 4 months after admission. The mortality rate of UC complicated by TM and DIC in elderly patients is high, necessitating rapid initiation of high-dose steroid administration or surgical treatment.

Aged↗
PubMed2000

Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon.

Our previous study showed that gamma interferon (IFN-gamma), a T-helper 1 (Th1)-type cytokine, plays a detrimental role in Staphylococcus aureus infection in mice. In this study, the role of Th2-type cytokines such as interleukin-4 (IL-4) and IL-10 in S. aureus infection was investigated. IL-10 mRNA was induced in parallel with IFN-gamma in the spleens and kidneys of mice during S. aureus infection, whereas IL-4 mRNA was induced in the spleens but not in the kidneys of these animals. Spleen cells obtained from S. aureus-infected mice produced lower titers of IFN-gamma and higher titers of IL-4 and IL-10 in response to heat-killed S. aureus than did those from uninfected mice. Administration of anti-IL-4 monoclonal antibody (MAb) or anti-IL-10 MAb inhibited the elimination of S. aureus cells from the kidneys of mice. IFN-gamma mRNA expression was enhanced in the spleens of anti-IL-4 MAb- or anti-IL-10 MAb-treated mice and also in the kidneys of anti-IL-4 MAb-treated animals. Next, we evaluated the role of IFN-gamma in S. aureus infection in IFN-gamma(-/-) mice. An increase in survival rates, a decrease in bacterial numbers in the kidneys, and an amelioration of histologic abnormalities in these organs were observed in IFN-gamma(-/-) mice compared with those in IFN-gamma(+/+) mice. Administration of MAb against IL-4 or IL-10 failed to affect bacterial growth in the spleens and kidneys of IFN-gamma(-/-) mice irrespective of the expression of Th2 response. These results suggest that S. aureus infection induced a Th2 response and that IL-4 and IL-10 might play a protective role through the regulation of IFN-gamma in S. aureus infection.

Animals↗
PubMed1988

Microbiological indications for the treatment of Staphylococcus aureus infections.

The Authors report microbiological data on the inhibitory activity of cephalothin, cefamandole, FCE 22101, gentamicin, netilmicin, amikacin, rifampicin, clindamycin, josamycin, ofloxacin, ciprofloxacin, vancomycin and teicoplanin against 165 clinically isolated Staphylococcus aureus strains. 34 of the study strains, i.e. 20.6%, were methicillin- and oxacillin-resistant. The activity of the tested drugs was good; the presence of nosocomial strains resistant to rifampicin (12.13%), clindamycin (13.94%), josamycin (18.2%), ofloxacin (4.85%), ciprofloxacin (12.7%), gentamicin (27.3%), amikacin (9.7%), netilmicin (7.9%) was noted. The Authors emphasize the good inhibitory activity of tested beta-lactam drugs against methicillin-sensitive Staphylococci, but also the limits of these drugs against methicillin-resistant strains. The activity of vancomycin and teicoplanin on all study strains was very good.

Anti-Bacterial Agents↗
PubMed1980

Plasmid profiles in epidemiologic studies of infections by Staphylococcus epidermidis.

Plasmid profiles of cultures of Staphylococcus epidermidis obtained by agarose gel electrophoresis were used, in conjunction with phage typing, biotyping, and antibiograms, in epidemiologic studies of infections in neonates and patients with cancer. In some cases, patients had cultures that were lysed by a single phage, belonged to the same biotype, and had identical antibiograms, but had distinctly different plasmid profiles. In other instances, almost identical plasmid profiles were observed in cultures lysed by a single phage, belonging to the same biotype, and with markedly different antibiograms. The plasmid profile technique was valuable in detecting distinct strains of S. epidermidis, and its use could be helpful in epidemiologic studies of infections by other organisms.

Bacteriological Techniques↗
PubMed1987

Ciprofloxacin treatment of Staphylococcus aureus infections.

Ciprofloxacin appears to be safe and effective for a wide variety of clinical infections. In-vitro and animal studies point to high cure rates for both methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections. Seventeen patients with staphylococcal infections severe enough to require hospital admission and initial parenteral therapy were treated with ciprofloxacin; the results were poor, with clinical failure in five and bacteriological failure in 12. All pathogens isolated were susceptible to ciprofloxacin both before and after therapy and tolerance was not detected. Further study is required before ciprofloxacin can be recommended for life threatening staphylococcal infections.

Adolescent↗
PubMed2003

Pharmacodynamics of oritavancin (LY333328) in a neutropenic-mouse thigh model of Staphylococcus aureus infection.

The pharmacokinetics and pharmacodynamics of oritavancin (LY333328), a glycopeptide antibiotic with concentration-dependent bactericidal activity against gram-positive pathogens, in a neutropenic-mouse thigh model of Staphylococcus aureus infection were studied. Plasma radioequivalent concentrations of oritavancin were determined by using [(14)C]oritavancin at doses ranging from 0.5 to 20 mg/kg of body weight. Peak plasma radioequivalent concentrations after an intravenous dose were 7.27, 12.56, 69.29, and 228.83 micro g/ml for doses of 0.5, 1, 5, and 20 mg/kg, respectively. The maximum concentration of drug in serum (C(max)) and the area under the concentration-time curve (AUC) increased linearly in proportion to the dose. Neither infection nor neutropenia was seen to affect the pharmacokinetics of oritavancin. Intravenous administration resulted in much higher concentrations in plasma than the concentrations obtained with subcutaneous administration. Single-dose dose-ranging studies suggested a sigmoid maximum effect (E(max)) dose-response relationship, with a maximal effect evident at single doses exceeding 2 mg/kg. The oritavancin dose (stasis dose) that resulted in a 24-h colony count similar to the pretreatment count was 1.53 (standard error [SE], 0.35) mg/kg. The single oritavancin dose that resulted in 50% of maximal bacterial killing (ED(50)) was 0.95 (SE, 0.20) mg/kg. Dose fractionation studies suggested that single doses of 0.5, 1, 2, 4, and 16 mg/kg appeared to have greater bactericidal efficacy than the same total dose subdivided and administered multiple times during the 24-h treatment period. When using an inhibitory E(max) model, C(max) appears to correlate better with bactericidal activity than do the time during which the concentration in plasma exceeds the MIC (T>MIC) and AUC. These data suggest that optimal oritavancin dosing strategies will require regimens that favor high C(max) concentrations rather than long periods during which unbound concentrations in plasma exceed the MIC.

Animals↗
PubMed2004

Iron-source preference of Staphylococcus aureus infections.

Although bacteria use different iron compounds in vitGro, the possibility that microbes distinguish between these iron sources during infection has hitherto not been examined. We applied stable isotope labeling to detect source-specific iron by mass spectrometry and show that Staphylococcus aureus preferentially imports heme iron over transferrin iron. By combining this approach with computational genome analysis, we identified hts (heme transport system), a gene cluster that promotes preferred heme iron import by S. aureus. Heme iron scavenging by means of hts is required for staphylococcal pathogenesis in animal hosts, indicating that heme iron is the preferred iron source during the initiation of infection.

ATP-Binding Cassette Transporters↗
PubMed1982

Jaundice associated with nonhepatic Staphylococcus aureus infection. Does teichoic acid have a role in pathogenesis?

A previously healthy young man developed jaundice early in the course of a febrile illness caused by an unrecognized deep-seated Staphylococcus aureus abscess. The serum bilirubin level peaked 11 days before the abscess was discovered and drained. During this time the bilirubin level returned to normal, circulating immune complexes were detected, and the serum free teichoic acid antibody titer was elevated. Indirect immunofluorescent staining of liver tissue for teichoic acid revealed 2+ nuclear fluorescence of the hepatocytes. These findings suggested that circulating free teichoic acid was deposited in the liver and may have had an endotoxin-like effect in the hepatocytes. With the appearance of specific antibody in the serum, circulating teichoic acid was neutralized and further hepatic injury ceased.

Adult↗
PubMed2004

Temporin A soaking in combination with intraperitoneal linezolid prevents vascular graft infection in a subcutaneous rat pouch model of infection with Staphylococcus epidermidis with intermediate resistance to glycopeptides.

The efficacy of linezolid and temporin A in the prevention of prosthetic graft infection due to methicillin-resistant Staphylococcus epidermidis with intermediate resistance to glycopeptides was investigated in a subcutaneous rat pouch model. Linezolid and temporin A, alone or combined, greatly reduced the bacterial numbers compared to the effect with control drugs.

Acetamides↗