THE PHOSPHATE FRACTIONS OF STAPHYLOCOCCUS AUREUS-INFECTED MICE.
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Immunoblotting sera from 26 patients with septicemia due to an epidemic strain of methicillin-resistant Staphylococcus aureus (EMRSA-15), 6 of whom died, revealed an immunodominant EMRSA-15 antigen at 61 kDa. There was a statistically significant correlate (P < 0.001) between survival and immunoglobulin G to the 61-kDa band. The antigen was identified by sequencing positive clones obtained by screening a genomic expression library of EMRSA-15 with pooled sera from patients taken after the septicemic episode. Eluted antibody reacted with the 61-kDa antigen on immunoblots. The amino terminus was obtained by searching the S. aureus NCTC 8325 and MRSA strain COL databases, and the whole protein was expressed in Escherichia coli TOP 10F'. The derived amino acid sequence showed homology with ABC transporters, with paired Walker A and Walker B motifs and 73% homology to YkpA from Bacillus subtilis. Epitope mapping of the derived amino acid sequence with sera from patients who had recovered from EMRSA-15 septicemia delineated seven epitopes. Three of these epitopes, represented by peptides 1 (KIKVYVGNYDFWYQS), 2 (TVIVVSHDRHFLYNNV), and 3 (TETFLRGFLGRMLFS), were synthesized and used to isolate human recombinant antibodies from a phage antibody display library. Recombinant antibodies against peptides 1 and 2 gave logarithmic reductions in organ colony counts, compared with control groups, in a mouse model of the infection. This study suggests the potential role of an ABC transporter as a target for immunotherapy.
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A case control study on MRSA infection was carried out, with the purpose of evaluating the effect of age, gender, hypoalbuminemia, the limitation of activities of daily living (ADL), the administration of antibiotics and the use of the new cephems which include third generation cephalosporins and monobactam and carbapenems, on the occurrence of MRSA infection among the inpatients in a geriatric hospital. From April 1991 to March 1994, 285 patients underwent a bacterial culture in the various clinical aspects. 118 patients were positive for MRSA, who were then used as cases while 167 patients who were negative for MRSA were used as controls. The level of serum albumin and the ADL score were lower in the MRSA group than in the non-MRSA group (P < 0.01) while the number of antibiotics administered before bacterial culture was greater in the MRSA group than in the non-MRSA group (P < 0.01). The third generation cephems were more commonly used in the MRSA positive patients than the negative patients (P < 0.01). Even after controlling for the other factors, hypoalbuminemia (OR = 1.73, 95% CI = 1.27-2.36), the limited ADL (partially limited vs without limitation: OR = 1.88, 95% CI = 1.19-2.96, completely limited vs without limitation: OR = 2.50, 95% CI = 1.64-3.82), the use of antibiotics other than the third generation cephems (vs without antibiotics: OR = 1.73, 95% CI = 1.20-2.50) and the administration of the third generation cephems (vs without antibiotics: OR = 3.12, 95% CI = 2.16-4.50) increased the risk of MRSA infection.
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OBJECTIVES: To investigate the efficacy of levofloxacin in the prevention of vascular prosthetic graft infection in a rat model. METHODS: Graft infections were established in the subcutaneous tissue of 225 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis, two contaminated groups with intraperitoneal cefazolin prophylaxis, two contaminated groups with intraperitoneal teicoplanin prophylaxis and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or teicoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. RESULTS: The efficacy of levofloxacin against the methicillin-susceptible strain was not different to that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The combination levofloxacin-rifampin demonstrated to be similarly effective to the combination rifampin-teicoplanin and more effective than the combination rifampin-cefazolin against both strains. CONCLUSIONS: Rifampin-levofloxacin combination seems useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis.
Macrolides are the primary drugs of choice for a number of clinically significant infections in children. The clinical aspects of newer macrolides such as roxithromycin, clarithromycin, dirithromycin, flurithromycin, miocamycin, rokitamycin, azithromycin and RP 59500 are discussed in different pediatric infections including streptococcal infections (e.g. pharyngitis, otitis, pneumonia, skin infections), staphylococcus soft tissue infections, mycoplasma pneumonia, chlamydial infections as well as legionellosis and campylobacter enteritis. Also, incidences of adverse events in pediatric patients receiving different macrolides are indicated as well as the dosages in children. The advantages of newer macrolides are: lower dosages, b.i.d. or once daily dosage regimens, good intracellular and tissue penetration, better activity against gram-negative microorganisms (some) and a low rate of adverse reactions.
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BACKGROUND AND OBJECTIVE: In August 2001, a cluster of MRSA skin infections was detected in a correctional facility. An investigation was conducted to determine its cause and to prevent further MRSA infections. DESIGN: Case-control study. SETTING: A 200-bed detention center. PATIENTS: A case was defined as a detainee with a skin lesion from which MRSA was cultured from July 24 through December 31, 2001. Case-patients were identified by review of laboratory culture results and by skin lesion screening through point-prevalence survey and admission examination. Controls were randomly selected from an alphabetized list of detainees. INTERVENTION: Medical staff implemented measures to improve skin disease screening, personal hygiene, wound care, and antimicrobial therapy. RESULTS: Sixteen cases were identified: 11, 5, and 0 in the preintervention, peri-intervention, and postintervention periods, respectively. Seven case-patients and 19 controls were included in the case-control study. On multivariable analysis, working as a dormitory orderly (OR, 9.8; CI95, 0.74-638; P = .10) and a stay of longer than 36 days (OR, 6.9; CI95, 0.65-128.2; P = .14) were the strongest predictors for MRSA skin infection. The preintervention, peri-intervention, and postintervention MRSA infection rates were 11.6, 8.8, and 0 per 10,000 detainee-days, respectively. The rate of MRSA skin infections declined significantly between both the preintervention and peri-intervention periods and the postintervention period (P < .01 for both comparisons). CONCLUSIONS: MRSA skin disease can become an emergent problem in a correctional facility. Interventions targeted at skin disease screening, appropriate antimicrobial treatment, and hygiene may decrease the risk of acquiring MRSA infection in correctional facilities.
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MRSA infection or colonization developed in eleven patients with neoplastic disease including malignant lymphoma (5 cases), soft tissue sarcoma (2 cases), acute myeloblastic leukemia (one), myelodysplastic syndrome (one), multiple myeloma (one), and mesothelioma (one) at our ward from October to December 1999. The infections were pneumonia (six cases), enteritis (three), bacteremia (one), and wound infection (one). Ten of 11 cases received antimicrobial agent (s) during one month before isolation of MRSA, suggesting selection of MRSA. Five cases improved and survived, but six cases died of infection. At the isolation of MRSA, the neutrophil count (NC) of the alive cases was 1, 500/microliter or more but the NC of five cases who died was less than 1,000/microliter, especially less than 100/microliter in three cases who had just received a cancer chemotherapy. Pulsed-field gel electrophoresis, performed in 9 cases, showed an identical DNA-pattern of MRSA in 7 cases, indicating a nosocomial infection. Our method to prevent spread of MRSA targeting solely the patients with MRSA infection was obviously unsatisfactory. We should target also the cases of MRSA colonization and make an effort to wash hands more vigorously. Furthermore, radical reformation such as increasing single sick-rooms drastically and increasing the number of nursing staff is also required.
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The protein binding of vancomycin has been reported to range from less than 10 percent to 82 percent. We examined the binding of vancomycin in 34 patients (14 intravenous drug abusers, 10 burn patients, and 10 control patients) with Staphylococcus aureus infections. Blood samples were collected serially over an 8- or 12-hour dosing interval following a one-hour infusion. In vitro studies were also performed using albumin solutions of varying concentrations. Binding characteristics were determined through ultrafiltration with vancomycin concentrations analyzed for fluorescence polarization immunoassay. The unbound fraction of vancomycin ranged from 0.41 to 0.77 with a mean of 0.54 +/- 0.08. Unbound fractions was significantly correlated with serum albumin concentration (r = -0.344, p less than 0.046) and renal clearance (r = 0.394, p less than 0.021) but not with total body clearance or volume of distribution. In vitro data also showed an association between albumin concentration and unbound fraction (r = -0.94, p less than 0.017). Although vancomycin protein binding changes with serum albumin, this finding may have limited clinical significance.
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