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PubMed2006

Nosocomial and community-acquired meticillin-resistant Staphylococcus aureus infections in hospitalized patients (Spain, 1993-2003).

A series of annual surveys on the prevalence of infections in hospitalized patients in Spain was undertaken from 1993 to 2003 to describe clinical and demographic characteristics, trends and geographical variations in the proportion of meticillin-resistant Staphylococcus aureus (MRSA). A total of 8312 S. aureus infections in patients from 296 acute care hospitals pertaining to 17 regions in Spain were observed during the study period. Overall, 23.8% of these organisms were reported as meticillin resistant. The proportion of MRSA varied widely across regions and during the study period. Patients with nosocomial infections (NIs) had a two-fold higher prevalence of MRSA (31%) than patients with community-acquired infections (CAIs) (14%; P<0.001). Nevertheless, there was an increasing trend in the prevalence of MRSA isolates, both in patients with NI (from 22% to 41%; P<0.001) and with CAI (from 7% to 28%; P<0.001) throughout the 11-year period. Geographical variations over the last three years (2001-2003) show a centripetal gradient, with the lowest MRSA prevalence in south-west Spain and the highest MRSA prevalence in the central regions. Almost five-fold differences in MRSA proportions were seen between regions (range 10.3-54.5%). Compared with bloodstream infections, infections in other sites were more likely to be caused by MRSA (adjusted odds ratios for surgical site, urinary tract, skin and respiratory infections of 1.2, 1.2, 1.5 and 2.1, respectively).

Community-Acquired Infections↗
PubMed2001

Treatment of methicillin-resistant Staphylococcus epidermidis infection following repair of an ulnar fracture and humeroradial joint luxation in a horse.

A 27-month-old Rocky Mountain Horse was examined because of a fracture of the proximal portion of the ulna and luxation of the humeroradial joint (Monteggia fracture). Open reduction was performed, using a mechanical distractor, and the ulnar fracture was stabilized by application of a bone plate and screws. After surgery, the horse developed an infection of the surgical site, and bacterial culture of fluid from the surgical site yielded a pure growth of methicillin-resistant Staphylococcus epidermidis susceptible to oxytetracycline, erythromycin, rifampin, and vancomycin. Treatment with oxytetracycline did not result in a favorable clinical response. Therefore, the horse was treated systemically with vancomycin and rifampin, and vancomycin-impregnated polymethyl methacrylate beads were implanted at the surgical site. Six months after surgery, the horse was sound at a walk or trot, and bony union was evident on radiographs of the elbow joint.

Animals↗
PubMed2003

Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus infection.

A 57-year-old woman developed exacerbation of atopic dermatitis, fever, and nephrotic syndrome with microscopic hematuria. By bacteriological study, methicillin-sensitive Staphylococcus aureus (MSSA) was detected from each culture of pharyngeal mucus, stool, and blood samples. Renal biopsy specimens showed endocapillary proliferative glomerulonephritis with massive IgA deposition in the mesangium and along the capillary loops. After antistaphylococcal therapy with antibiotics, MSSA was negative for each culture and urinary protein decreased. Nine months after the first renal biopsy, a re-biopsy was performed, which revealed apparent disappearance of both endocapillary cell proliferation and IgA deposition. It is known that methicillin-resistant S. aureus (MRSA) infection causes glomerulonephritis through T-cell stimulation by superantigen presented by MRSA. The present results suggest that not only MRSA but also MSSA can cause this type of glomerulonephritis.

Anti-Bacterial Agents↗
PubMed1999

Susceptibility testing and clinical effect of fusidic acid in oxacillin-resistant Staphylococcus aureus infections.

One hundred and six oxacillin-resistant Staphylococcus aureus (ORSA) isolates collected from various clinical specimens at Mackay Memorial Hospital during the period from 1997 to 1998 were tested. The MICs of fusidic acid against ORSA isolates were in the range of 0.06 microgram/mL to 4 micrograms/mL. There was only one ORSA isolate (0.9%) resistant to fusidic acid in this study. Twenty-four patients with ORSA infection were enrolled into the study between July 1997 to June 1998. Four patients without the evidence of sepsis received oral fusidic acid only. The other 20 patients with sepsis received intravenous glycopeptide first, and then the oral fusidic acid for 7 to 10 days. Oral fusidic acid was used for mild ORSA infection and achieved satisfactory clinical outcome. In severe ORSA infection, it was found that sequential therapy with fusidic acid had relapsed in three patients. We concluded that oral fusidic acid achieved a satisfactory outcome in our patients with mild ORSA infection. In such cases, fusidic acid may provide an effective alternative treatment of choice. The rare side effect of granulocytopenia and jaundice was noted in our case series. The side effect may be not so rare as previously thought, if it had been carefully looked for.

Adult↗
PubMed2005

A novel peptide isolated from phage library to substitute a complex system for a vaccine against staphylococci infection.

Staphylococcus aureus is a major human pathogen and many of the strains are resistant to conventional antibacterial treatment. The bacteria cause disease largely due to the production of multiple toxins, whose synthesis is controlled by an RNA molecule termed RNAIII. The production of RNAIII is induced by quorum sensing systems, one of them containing the protein RNAIII activating protein (RAP). Here we show that we partially purified supernatant of S. aureus, used this fraction to vaccinate mice, and selected antibody-binding peptides by phage display. Mice were vaccinated with the various peptides and challenged with S. aureus. One of the binding peptide termed R13 induced a protective immune response. Western blot analysis showed that the anti-R13 antibodies specifically bind to native or recombinant RAP. Mice vaccinated with R13 were protected and protection was sustained for the duration of the 6-month study period. Our results show that R13 could be used as a long-term effective protective-peptide-vaccine to prevent S. aureus infections and once again show that targeting the RAP quorum sensing system is an effective approach to preventing staphylococcal infections. In addition our studies show that selection of specific protective peptides by phage display using sera induced by complex antigens is a rapid and effective way to identify the protective antigen and select for a peptide vaccine.

Animals↗
PubMed2000

Pharmacodynamics of glycopeptides in the mouse peritonitis model of Streptococcus pneumoniae or Staphylococcus aureus infection.

The emergence of resistance to various antibiotics in pneumococci leaves the glycopeptides as the only antibiotics against which pneumococci have no resistance mechanism. This situation has led to a renewed interest in the use of glycopeptides. It has not yet been possible to conclude which one or more of the pharmacokinetic or pharmacodynamic (PK/PD) parameters are the most important and best predictors for the effects of treatment with glycopeptides in animal models or in humans. We used the mouse peritonitis model with immunocompetent mice and with Staphylococcus aureus and Streptococcus pneumoniae as infective organisms. A wide spectrum of different treatment regimens with vancomycin and teicoplanin was tested to study the pharmacodynamics of these drugs. In studies in which the single dose that protected 50% of lethally infected mice (ED(50)) was given as one dose or was divided into two doses, survival was significantly decreased when the dose was divided. The only statistically significant correlations between the percentage of survival of the mice after 6 days and each of the PK/PD parameters were for peak concentration (C(max))/MIC and S. aureus and for the free fraction of C(max) (C(max-free))/MIC and S. pneumoniae. For S. pneumoniae, the ED(50) for different dosing regimens increased with the number of doses given; e.g., the single-dose ED(50)s for vancomycin and teicoplanin were 0.65 and 0. 45 mg/kg, respectively, but the ED(50)s for dosing regimens with 2-h doses given for 48 h were 6.79 and 5.67 mg/kg, respectively. In experiments with 39 different vancomycin dosing regimens and 40 different teicoplanin dosing regimens against S. pneumoniae, the different PK/PD parameters were analyzed using logistic regression. The C(max-free)/MIC was one of two parameters that best explained the effect for both drugs; for vancomycin, the other important parameter was the AUC/MIC, and for teicoplanin, the other parameter was the time the free fraction of the drug is above the MIC. The effect analyzed as a function of C(max-free)/MIC disclosed thresholds with shifts from almost no effect to full effect at ratios of five to six for vancomycin and two to three for teicoplanin.

Animals↗
PubMed2004

Dosage regimen of arbekacin for methicillin-resistant Staphylococcus aureus infection in newborns and infants.

BACKGROUND: Arbekacin (ABK) is an aminoglycoside antibiotic that has a dose-dependent bactericidal action. Because it inhibits the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus (MRSA), it has attracted attention as a therapeutic drug for MRSA infection. In this study, the authors investigated the pharmacokinetics of ABK based on therapeutic drug monitoring (TDM), in order to establish an effective dosage regimen with minimal adverse reactions in MRSA infected newborns and infants. METHODS: Arbekacin was administered to nine MRSA infected newborns and infants between October 2000 and March 2002. Following the initial ABK administration, blood was collected and the blood concentration of ABK was measured. The blood concentrations of ABK were analyzed by the two-compartment model or by a model-independent method in order to elucidate the pharmacokinetics of ABK. Pharmacokinetic analysis was performed using WinNonlin Professional V3.1. RESULTS: The mean age at initial ABK administration was 24.0 +/- 26.0 days (postconceptional age: 39.2 +/- 3.9 weeks). The increase in the peak blood concentration of ABK was 2.40 +/- 0.20 microg/mL per mg ABK per kg bodyweight, showing great consistency among cases. The elimination half-life of ABK was 0.22-3.52 h in the alpha phase (T(1/2alpha)) and 2.42-33.44 h in the beta phase (T(1/2beta)), showing great variation among cases. The distribution volume was 0.75 +/- 0.13 L/kg, and systemic clearance was 0.054 +/- 0.012 L/h/kg. ABK alleviated clinical symptoms and inflammations in all cases. CONCLUSION: Nine newborns and infants with MRSA infection and various underlying diseases were successfully treated with TDM-based administration of ABK with no severe adverse reactions.

Aminoglycosides↗
PubMed2001

Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure.

A 58-year-old man developed proteinuria and renal dysfunction following pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin was administered, and prednisolone pulse therapy and plasmapheresis were performed. Subsequently, serum creatinine was decreased. Eight months later, creatinine and CRP were again elevated, and MRSA was detected. Vancomycin was again administered and plasmapheresis was performed. However, renal function was not improved and continuous hemodialysis was initiated. This case indicates that complete eradication of MRSA is necessary to treat MRSA-associated glomerulonephritis, and if this is not attained, a permanent loss of renal function occurs.

Anti-Bacterial Agents↗
PubMed1992

[The effect of bacterial interference phenomena in experimental Staphylococcus hyicus infections of gnotobiotic piglets].

The prevention of exudative epidermitis could be confirmed in experimental investigations with gnotobiotic piglets when the skin first was colonized with avirulent strains of Staphylococcus (Staph.) hyicus and subsequently exposed to virulent strains of Staph. hyicus. However, locally restricted cutaneous lesions in the area of application corresponding to exudative epidermitis were seen in five of nine piglets. Using the strain Staph. sciuri the spread of virulent Staph. hyicus could not be suppressed. Such infected two piglets developed generalized exudative epidermitis. In another experiment with four piglets it could be shown, that the relative protective mechanism correlating to bacterial interference on the one hand can be influenced by the virulence of causative organisms. On the other hand it even can be abolished when skin lesions are involved. For that reason probably the utilization of bacterial interference in prevention of exudative epidermitis under field conditions is considerably limited.

Animals↗
PubMed2001

Two-staged operation for thoracolumbar osteomyelitis following methicillin-resistant staphylococcus aureus infection of a craniectomy wound--case report.

A previously healthy 53-year-old woman developed pyogenic vertebral osteomyelitis (PVO) manifesting as progressive lumbago following wound infection of a decompressive craniectomy performed for brain contusion caused by a traffic accident. Magnetic resonance imaging disclosed vertebral osteomyelitis at T-12 and L-1 with paravertebral abscess. Anterior debridement and fusion using autografts were performed at the first operation. Methicillin-resistant Staphylococcus aureus (MRSA) was cultured from the abscess specimen. Antibiotic therapy resolved the infection. Pedicle screw fixation was performed at the second operation. The patient became free from back pain and no recurrence of infection was seen. The diagnosis of PVO is frequently observed or delayed because of the nonspecific symptomatic presentation in the early stage. Coexistent infection or trauma makes early diagnosis more difficult. Indications and timing of instrumentation for the spinal column infected with MRSA is difficult. Two-staged operation with anterior debridement and posterior instrumentation after eradication of the infection is a safe and effective procedure for MRSA vertebral osteomyelitis.

Craniotomy↗
PubMed1998

[Correlation in Staphylococcus aureus infections between toxic shock syndrome toxin-1 production and clinical feature].

Toxic shock syndrome (TSS) is caussed by toxic shock syndrome toxin-1 (TSST-1) of Staphylococcus aureus. We studied the incidence of TSST-1 production by the clinical isolates of S. aureus, in order to clarify the possibility of TSS caused by S. aureus. One hundred and seventeen clinical isolates of S. aureus were tested. Of 117 strains, 74 were methicillin-cephem resistant S. aureus (MRSA), and 43 were methicillin-cephem sensitive S. aureus (MSSA). TSST-1 production and penicillinase (PCase) activity were measured by means of reversed passive Latex aggulutination method and acidmetric assay, respectively. The incidences of TSST-1 production by PCase positive MRSA, PCase negative MRSA, PCase positive MSSA and PCase negative MSSA were 92% (55/60), 78% (11/14), 21% (7/33) and 0% (0/10), respectively. TSS occurred in a patient with chronic complicated pyelonephritis after endopyelotomy for hydronephrosis. In this patient, PCase positive MRSA which produced TSST-1 was isolated from urinary tract, and he was cured after administration of arbekacin. These results indicsate that methicillin-cephem resistance and PCase production are the risk factors for TSST-1 production in S. aureus.

Bacterial Toxins↗
PubMed2006

Drotrecogin alfa (activated) for nonmenstrual toxic shock syndrome associated with methicillin resistant Staphylococcus aureus infection.

Nonmenstrual toxic shock syndrome (TSS) due to Staphylococcus aureus can lead to significant morbidity and mortality. While drotrecogin alfa (DA) has been employed in patients with Methicillin-resistant Staphylococcus aureus (MRSA) severe sepsis and septic shock, its utility in TSS remains unclear. The authors report a case of severe sepsis in the setting of MRSA-associated TSS that responded to treatment with DA. This case illustrates a potential role for DA in the treatment of toxic shock syndromes and emphasizes the importance of aggressive diagnostic and therapeutic modalities in approaching these conditions.

Anti-Bacterial Agents↗
PubMed1998

In vitro resistance to thrombin-induced platelet microbicidal protein is associated with enhanced progression and hematogenous dissemination in experimental Staphylococcus aureus infective endocarditis.

We examined the influence of thrombin-induced platelet microbicidal protein 1 (tPMP-1) on the progression and hematogenous dissemination of experimental endocarditis caused by isogenic Staphylococcus aureus strains differing in tPMP susceptibility (tPMPs) or resistance (tPMPr) in vitro. Following simultaneous challenge of animals with both strains, significantly higher tPMPr bacterial densities were present in vegetations (P < 0.0001), kidneys (P < 0. 0001), and spleens (P < 0.0001) compared with those for the tPMPs strain. These data indicate that tPMP-1 limits the intravegetation proliferation and hematogenous dissemination of a tPMPs strain in experimental endocarditis, while the tPMPr phenotype confers a selective advantage associated with the enhanced progression of this infection.

Animals↗
PubMed2003

[Successful treatment with linezolid in two cases of methicillin-resistant Staphylococcus aureus infections in the orthopedic field].

We have reported two orthopedic patients with Methicillin-resistant Staphylococcus aureus (MRSA) infections successfully treated with linezolid. The first case was a 64-years-old man with bacteremia, spondylitis and psoas abscesses caused by MRSA. He was treated with arbekacin (ABK) and vancomycin (VCM), and then became afebrile. However he complained of a recurrence of fever and oliguria, we administered linezolid for two weeks intravenously because of fluctuating renal dysfunction. Thereafter his clinical conditions improved. The second case was a 26-years-old man with MRSA infection of the pelvis after a trauma. He was treated with teicoplanin (TEIC) for two weeks. However the minimum inhibiratory concentrations (MICs) of TEIC and VCM against MRSA, isolated from the wounds, were 4 micrograms/ml each, we administered linezolid intravenously and the patient was successfully treated in four weeks. Linezolid has been proven to have high efficacy against MRSA by some trials abroad. But the agent has the indication only for VRE by the Medical Insurance in Japan. These cases also suggest that linezolid is useful for MRSA infections in these cases.

Acetamides↗