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PubMed2006

[Optimal vancomycin serum level in Staphylococcus aureus infections?].

Vancomycin is the cornerstone of therapy against methicillin-resistant Staphylococus aureus in both community and nosocomial-acquired infections. Because vancomycin is a concentration-independent or time-dependant antibiotic, most clinicians have abandoned the routine practice of determining peak serum concentrations to rely solely on monitoring serum concentrations. The so-called therapeutic range most often quoted for vancomycin was assessed for through serum concentrations of 5-10 mg/l. But prolonged exposure to serum concentration close to the MIC is associated with the emergence of resistance. More recent guidelines recommended vancomycin in concentrations of 15-20 mg/l for the treatment of severe Staphylococcus infections or in situations where vancomycin penetration is poor. However, because of the great variability of vancomycin MIC(S) (0,12-4 mg/l) of susceptible Staphylococcus strains, guidelines should recommend through serum concentrations of 5-10 times the MIC.

Anti-Bacterial Agents↗

PubMed2006

Meticillin-resistant Staphylococcus aureus infection in diabetic mice enhanced inflammation and coagulation.

BALB/cA mice were used to study the interaction of diabetes and meticillin-resistant Staphylococcus aureus (MRSA) infection on pathogen distribution, cytokine profile and inflammatory and endothelial-injury markers, as well as coagulation and anticoagulation factors. Meticillin-susceptible S. aureus (MSSA) infection did not cause death within the experimental period. MRSA-infected nondiabetic and diabetic mice died on 19.1+/-1.4 and 10.6+/-0.7 days post-infection (p.i.), respectively. MRSA and MSSA infection in diabetic mice did not result in symptomatic bacteraemia; however, MRSA infection in diabetic mice significantly reduced glucose levels (P<0.05). Diabetic mice showed significantly higher levels of C-reactive protein, fibrinogen, fibronectin and von Willebrand factor than nondiabetic mice (P<0.05), and MRSA infection further elevated the plasma levels of these inflammatory and endothelial markers (P<0.05). Before infection, diabetic mice had significantly higher plasminogen activator inhibitor-1 (PAI-1) activity, lower antithrombin III (AT-III) and protein C activities (P<0.05), and MRSA infection significantly increased PAI-1 activity further and reduced the activity of AT-III and protein C (P<0.05). MRSA infection increased the production of three Th1 cytokines, interleukin 2 (IL-2), tumour necrosis factor alpha and gamma interferon, in diabetic mice (P<0.05); however, three Th2 cytokines, IL-4, IL-6, IL-10, were elevated at 2 and 4 days p.i., and then dropped gradually. MRSA infection in diabetic mice accelerated the inflammation process, endothelial injury and blood coagulation in diabetic mice. Therefore, the development of proper infection diagnosis and timely use of effective treatments for MRSA-infected diabetic individuals is important and necessary.

Animals↗

PubMed1996

Intracellular demonstration of active TGFbeta1 in B cells and plasma cells of autoimmune mice. IgG-bound TGFbeta1 suppresses neutrophil function and host defense against Staphylococcus aureus infection.

Infection remains a leading cause of morbidity and mortality in patients with SLE. To investigate this, previously we assessed the host defense status of autoimmune MRL/lpr mice and found that elaboration of active TGFbeta suppressed neutrophil function and decreased survival in response to Staphylococcus aureus infection. The purpose of the present work was to elucidate the molecular form and the cellular source of the active TGFbeta involved. Here, we report for the first time that TGFbeta1 is found in the active form inside B cells and plasma cells and that it circulates in the plasma complexed with IgG in two murine models of systemic autoimmunity and in some patients with SLE. IgG-bound active TGFbeta1 is many times more potent than uncomplexed active TGFbeta1 for suppression of neutrophil function in vitro and host defense against S. aureus infection in vivo. These data indicate that TGFbeta1 is in the active form inside B cells and plasma cells, that the formation of a complex of IgG and active TGFbeta1 is greatly accelerated in autoimmunity, and that this complex is extremely potent for suppression of PMN function and host defense against bacterial infection.

Animals↗

PubMed2000

[A successfully repaired case of methicillin-resistant Staphylococcus aureus infective endocarditis in a girl with VSD].

We report a successful case of active infective endocarditis due to Methicilin-Resistant Staphylococcus aureus (MRSA). A 2-year-old girl who had a ventricular septal defect (VSD) complained of persistent fever. Echocardiography showeda large vegetation on the tricuspid valve and a small VSD. She underwent vegetectomy, tricuspid valvoplasty and direct closure of VSD. Vancomycin treatment was also effective to abolish infection. She was discharged without any complication.

Child, Preschool↗

PubMed1980

Protective effect in the lactating bovine mammary gland induced by coagulase-negative staphylococci against experimental Staphylococcus aureus infections.

The susceptibility of quarters preinfected either experimentally with Staphylococcus epidermidis or Staphylococcus xylosus or naturally by other coagulase-negative staphylococci was measured after challenge with two different strains of Staphylococcus aureus. The proportion of infected control quarters (95%) was raised significantly higher than that of those preinfected by the coagulase-negative staphylococci (24.5%). Differences were observed in the frequency of superinfection of the quarters according to the strain of the preinfective coagulase-negative staphylococcus, duration of preinfection and somatic cell count at the time of challenge. The protective mechanism against Staph. aureus induced by preinfection with coagulase-negative staphylococci is discussed.

Animals↗

PubMed1998

Fatal Staphylococcus aureus infective endocarditis: the dental implications.

Infective endocarditis remains an important and life-threatening infection despite improvements in diagnosis and management. There is currently a greater role for nosocomial acquisition of organisms and immunosuppression in the pathogenesis of this disease and emergence of a broader spectrum of infective organisms including those not commonly isolated from the mouth such as staphylococci. We report a case of infective endocarditis caused by Staphylococcus aureus in which the patient developed disseminated intravascular coagulation and multiple septic infarcts resulting in a frontal lobe brain abscess. Multiple dental extractions were complicated by delayed postextraction hemorrhage and the immediate cause of death was abdominal hemorrhage. The dental management in infective endocarditis should be planned in consultation with the attending physician, and should take into account both the causative organism and the presence of complications. When the oral cavity cannot be proven as the bacterial source for infective endocarditis, the immediate dental management should be directed toward improving the patient's oral hygiene and providing pain relief. Definitive long-term treatment, including any extractions, is ideally delayed until the patient has fully recovered from the infective endocarditis and its attendant complications.

Brain Abscess↗

PubMed1998

Outbreaks of Staphylococcus aureus infections during treatment of late onset pneumonia with ciprofloxacin in a prospective, randomized study.

We carried out a prospective, randomized four-center study in nosocomial pneumonia to evaluate the clinical and microbiological efficacy and safety of different treatment regimens in adult intensive care patients. During the randomized treatment of 18 patients with late onset pneumonia, ciprofloxacin (CIP) was compared to ceftazidim plus gentamicin (CAZ/GM), outbreaks of Staphylococcus aureus infections occurred in center 1. This article reports the unexpected findings. In the CIP group six out of ten patients were superinfected or reinfected with ciprofloxacin-resistant pathogens at the follow-up on day 5 after treatment. Four out of these six patients were superinfected with methicillin-susceptible or methicillin-resistant S. aureus (MRSA). Four superinfected patients died with pneumonia during treatment or before the follow-up. In the CAZ/GM group one out of eight patients was superinfected with MRSA. One patient died with pneumonia during treatment. There was no problem with multiresistant S. aureus or MRSA before the study period in center 1. In conclusion, we observed outbreaks of S. aureus infections during the treatment of late onset pneumonia with ciprofloxacin, which were associated with a high mortality. These superinfections occurred in mechanically ventilated, postoperative cardiac surgical patients after 13 days in the intensive care unit (ICU). We recommend combining ciprofloxacin with an antibiotic agent active against gram-positive bacteria in ventilator-associated pneumonia after a prolonged ICU stay. Selective pressure of ciprofloxacin could have played a role in these superinfections.

APACHE↗

PubMed1999

Altered immune responses and susceptibility to Leishmania major and Staphylococcus aureus infection in IL-18-deficient mice.

IL-18, formerly designated IFN-inducing factor, is a novel cytokine produced by activated macrophages. It synergizes with IL-12 in the induction of the development of Th1 cells and NK cells. To define the biological role of IL-18 in vivo, we have constructed a strain of mice lacking IL-18. Homozygous IL-18 knockout (-/-) mice are viable, fertile, and without evident histopathologic abnormalities. However, in contrast to the heterozygous (+/-) or wild-type (+/+) mice, which are highly resistant to the infection of the protozoan parasite Leishmania major, the IL-18-/- mice are uniformly susceptible. The infected IL-18-/- mice produced significantly lower levels of IFN-gamma and larger amounts of IL-4 compared with similarly infected +/- and +/+ mice. In contrast, when infected with the extracellular Gram-positive bacteria Staphylococcus aureus, the IL-18-/- mice developed markedly less septicemia than similarly infected wild-type (+/+) mice. However, the mutant mice developed significantly more severe septic arthritis than the control wild-type mice. This was accompanied by a reduction in the levels of Ag-induced splenic T cell proliferation, decreased IFN-gamma and TNF-alpha synthesis, but increased IL-4 production by the mutant mice compared with the wild-type mice. These results therefore provide direct evidence that IL-18 is not only essential for the host defense against intracellular infection, but it also plays a critical role in regulating the synthesis of inflammatory cytokines, and therefore could be an important target for therapeutic intervention.

Animals↗

PubMed2004

Methicillin-resistant Staphylococcus aureus infection in the Texas prison system.

Recent reports indicate that correctional facility inmates may be at elevated risk for contracting methicillin-resistant Staphylococcus aureus (MRSA) infection because of overcrowding, poor hygiene, and high rates of diseases causing immunosuppression. The present study of 299,179 Texas inmates who were incarcerated between 1999-2001 indicated an incidence of 12 MRSA infections/1000 person-years. Inmates with circulatory disease, cardiovascular disease, diabetes, end-stage liver disease, end-stage renal disease, human immunodeficiency virus infection or acquired immunodeficiency syndrome, and skin diseases all exhibited elevated rates of MRSA infection.

Adult↗

PubMed1996

Use of restriction endonuclease analysis of plasmids and pulsed-field gel electrophoresis to investigate outbreaks of methicillin-resistant Staphylococcus aureus infection.

We used restriction endonuclease analysis of plasmids (REAP) and pulsed-field gel electrophoresis (PFGE) to investigate clusterings of methicillin-resistant Staphylococcus aureus (MRSA) infections in our orthopedic unit, neurosurgery unit, intensive care unit, and burn unit. Fourteen different strain types were identified by REAP and 10 different strain types were identified by PFGE among 25 MRSA isolates collected during these incidents of infection. Though neither technique was clearly superior to the other for typing MRSA isolates, REAP is recommended as a relatively simple and reproducible technique for the preliminary investigation of MRSA infection outbreaks in clinical settings.

Bacterial Typing Techniques↗

PubMed2003

Trimethoprim/sulfamethoxazole for treatment of severe Staphylococcus aureus infections.

OBJECTIVE: To evaluate the role of trimethoprim/sulfamethoxazole (TMP/SMX) as an alternative to vancomycin for the treatment of severe Staphylococcus aureus infections. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-February 2003) and EMBASE (1980-February 2003). Key search terms included trimethoprim/sulfamethoxazole combination and Staphylococcus aureus. DATA SYNTHESIS: An evaluation of case reports, case series, and clinical studies focusing on the use of TMP/SMX for treatment of severe S. aureus infections was conducted. The majority of the reports indicate that TMP/SMX may be effective for the treatment of infections due to low bacterial burdens of susceptible strains of S. aureus. CONCLUSIONS: In select infections, TMP/SMX may be a useful alternative to vancomycin for treatment of severe S. aureus infections. Additional randomized studies should be conducted comparing this agent with vancomycin and linezolid.

Adult↗

PubMed2005

Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice.

The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence.

Animals↗

PubMed1999

Investigation of suspected nosocomial clusters of Staphylococcus haemolyticus infections.

OBJECTIVE: To determine whether typing methods can discriminate among Staphylococcus haemolyticus isolates. DESIGN: Molecular epidemiological evaluation of S. haemolyticus isolates obtained from patients hospitalized on a hematology service and in a surgical intensive-care unit (SICU). SETTING: A large Midwestern teaching hospital. INTERVENTIONS: None. RESULTS: Over 22 days, S. haemolyticus was isolated from five patients on the hematology service. Isolates from four patients had the same unusual antibiogram and biotype. Ribotyping, restriction endonuclease digestion of plasmid DNA (REAP), and whole chromosomal DNA analysis by pulsed-field gel electrophoresis (PFGE) confirmed that these isolates were identical and different from the fifth patient's isolate and from 6 control isolates. In a second cluster, 11 S. haemolyticus isolates obtained from eight patients in the SICU had similar antibiograms and biotypes. By REAP and ribotype analysis, isolates from four patients were identical. However, PFGE indicated that only two of these patients shared a common strain. CONCLUSIONS: Antibiograms or biotyping may discriminate among isolates of S. haemolyticus if the results of these tests are unusual. Many clinical isolates can be differentiated by REAP analysis, ribotyping, or PFGE. However, some isolates are identical by all of these methods, suggesting that they may have been transmitted nosocomially.

Cross Infection↗

PubMed1994

Staphylococcus aureus infection on experimental croton oil-inflamed skin in mice.

Staphylococcus aureus cells were inoculated on the surface of skin inflamed by application of croton oil in cyclophosphamide-treated mice. Skin specimens were taken at 1, 3, 6, 12, and 24 h inoculation and each specimen was examined by microscopy. The S. aureus cells which attached to the surface of the skin immediately after inoculation had invaded the horny layer within 1 h. The cells gradually penetrated deeper into the epidermis. Electron microscopy revealed fibril-like structures around the S. aureus cells and the cells which adhered to the horny layer and fibrin by means of Ruthenium red-positive, fibril-like structures. A combined application of 0.1% gentamicin ointment, 2% fusidic acid ointment, and clobetasol propionate ointment was more effective in decreasing the number of S. aureus cells in the lesions than was an application of clobetasol propionate ointment alone. However, a combined application of 0.1% gentamicin ointment and 2% fusidic acid ointment without clobetasol propionate ointment showed almost the same efficacy as that with clobetasol propionate ointment. Although povidone iodine killed S. aureus in vitro at a concentration of 0.01% (100 micrograms/ml) in 40 s, its in vivo efficacy was limited.

Animals↗

PubMed2002

In catheter infections by Staphylococcus epidermidis the intercellular adhesion (ica) locus is a molecular marker of the virulent slime-producing strains.

Recently, it has been shown that S. epidermidis includes the ica operon responsible for slime production. In the operon, coexpression of icaA and icaD genes is required for full slime synthesis. In this study, the presence of icaA and icaD genes was searched for in a collection of 100 Staphylococcus epidermidis strains from catheter-associated infections by an original PCR method. Another 51 strains of S. epidermidis isolated from the skin or mucosa of healthy volunteers (26 of which derived from the hospital staff) were also investigated. Slime-forming ability was phenotypically tested on Congo red agar plates. Sixty-one percent of the strains isolated from catheters were icaA- icaD-positive and produced slime. The results indicate that detection of ica genes by a PCR method is a useful tool for prompt identification of S. epidermidis slime-forming strains isolated from catheter-related infections. Also, three saprophytic strains from the hospital staff were positive for slime synthesis and presence of ica genes, suggesting a potential diffusion of slime-forming strains in hospital personnel.

Biomarkers↗

PubMed1992

Detection of teichoic acid antibodies in Staphylococcus aureus infections.

A commercially available agar gel diffusion (AGD) assay was used to investigate the teichoic acid antibody (TAA) response in 183 patients with proven Staphylococcus aureus (SA) infections. Two control groups were also investigated. One consisted of 100 hospitalized patients with a variety of medical and surgical conditions other than SA infection and the other consisted of 116 healthy hospital staff members. The sensitivity of the AGD assay varied markedly depending on the site of infection in the patients with proven SA infections. All patients with SA endocarditis developed positive TAA titres (greater than or equal to 1:4), although more than one third of these were initially negative. In patients with chronic osteomyelitis or septic arthritis, 41% had positive TAA titres, whereas no positive titres were detected in patients with acute osteomyelitis or septic arthritis. Lower rates of positive TAA titres were found in patients with deep abscesses (27%), pneumonia (14%) and post-operative infections (9%), but no positive titres occurred in patients with acute uncomplicated bacteremia, cellulitis or meningitis. In 100 hospitalized control patients, no positive titres were detected, and only 1 of 116 (0.9%) healthy hospital staff controls was positive. Suggested guidelines for the use of the AGD assay are discussed.

Adolescent↗

PubMed2000

Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection.

Toll-like receptor (TLR) family acts as pattern recognition receptors for pathogen-specific molecular patterns. We previously showed that TLR2 recognizes Gram-positive bacterial components whereas TLR4 recognizes LPS, a component of Gram-negative bacteria. MyD88 is shown to be an adaptor molecule essential for TLR family signaling. To investigate the role of TLR family in host defense against Gram-positive bacteria, we infected TLR2- and MyD88-deficient mice with Staphylococcus aureus. Both TLR2- and MyD88-deficient mice were highly susceptible to S. aureus infection, with more enhanced susceptibility in MyD88-deficient mice. Peritoneal macrophages from MyD88-deficient mice did not produce any detectable levels of cytokines in response to S. aureus. In contrast, TLR2-deficient macrophages produced reduced, but significant, levels of the cytokines, and TLR4-deficient macrophages produced the same amounts as wild-type cells, indicating that S. aureus is recognized not only by TLR2, but also by other TLR family members except for TLR4.

Adaptor Proteins, Signal Transducing↗

PubMed1992

Community-acquired methicillin-resistant Staphylococcus aureus infections in otolaryngology.

Soon after the introduction of methicillin, strains of Staphylococcus aureus resistant to methicillin were reported. Methicillin-resistant Staphylococcus aureus (MRSA) has become a common hospital pathogen, often resistant to multiple antibiotics, while causing significant morbidity and mortality. Community-acquired MRSA infections have been infrequently documented. Most reports have been associated with intravenous drug abuse. This report reviews 15 patients with community-acquired MRSA infections of the head and neck. None admitted to intravenous drug use. Additionally, no patient was known to be a healthcare worker. The MRSA strains showed antibiotic susceptibility and resistance profiles different from typical hospital-acquired MRSA isolates. All but one infection resolved with adequate surgical or appropriate antibiotic therapy. Clinicians should become aware of the possibility of community-acquired MRSA in the patient who has had continued infection despite antibiotic therapy.

Abscess↗