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Continuous infusion of vancomycin in methicillin-resistant staphylococcus infection.

OBJECTIVE: The aim of the study was to verify the therapeutic response of vancomycin in methicillin-resistant staphylococcus infection (MRSA/ MRCNS) administered according to two different methods (intermittent infusion vs. continuous infusion). METHOD: Experimental plan: retrospective study; study environment: university hospital, two intensive care units. Twenty-five critically ill patients submitted to antibiotic treatment with vancomycin for infection from MRSA/MRCNS were studied. The patients, who were classified according to SAPS II scores, were divided into two groups: group A (n = 14): dose of vancomycin of 0.5 g x 4/day and group B (n = 11): dose of 2 g/day of vancomycin administered in a continuous infusion. Before the antibiotic therapy was started (T1) and prior to its end (T2), the following parameters were evaluated: degree of impairment of the main organs and systems by means of sepsis-related organ failure assessment score (SOFA) and count of the white blood cells (WBC). The length of the hospital stay during intensive care was calculated for both groups (statistics: Student t test). RESULTS: No significant differences were found in the SAPS II scores and in the length of the hospital stay. In a comparison of the T1 and T2 results, we noted that patients of group A had no variations in the SOFA scores (4.84 +/- 2.48 vs. 4 +/- 3.9) and in the WBC mean values (12,415 +/- 5,099 vs. 12,841 +/- 6,864 cells/mm3). In contrast, in the patients of group B, we noted significant variations (p < 0.05) in the mean values of the SOFA scores (6.62 +/- 2.2 vs. 4.37 +/- 3.5) and in the mean values relative to the WBC count (17,242 +/- 12,842 vs. 10,757 +/- 3,610 cells/mm3). CONCLUSIONS: In critically ill patients suffering from MRSA/MRCNS infection, vancomycin administration in continuous infusions improved organ function and leukocyte response, but did not seem to modify the overall evolution of the disease.

Adult↗

[Drug resistance analysis of staphylococcus infection in our hospital from 2003 to 2005].

OBJECTIVE: To explore the change in mobility of staphylococcus and its drug resistance etiology investigation and clinical treatment. METHODS: The routine biochemical identification was used for staphylococcus differentiation. Minimal inhibitory concentrations was used for drug-resistance determination. Some drug-resistance determination were detected by K-B method. The inducible resistance of erythromycin to clindamycin was checked by D-test. RESULTS: Staphylococcus was in the first place in the hospital infection. The rates of methicillin-resistant staphylococcus were 54.1%. The drug-resistance rates of staphylococcus to penicillin, oxacillin, erythromycin, tetracycline, ciprofloxacin, gentamicin, clindamycin, SMZCO, chloramphenicol, vancomycin, teicoplanin antibacterials were 93.2%, 54.1%, 85.1%, 56.7%, 45.9%, 48.6%, 58.1%. 45.9%, 31.1%, 0%, 0%. D-test positive rate was 37.9%. CONCLUSIONS: The results are helpful in study of pathogenic bacteria and drug resistance characteristics in staphylococcus infection.

Anti-Bacterial Agents↗

Ambulatory treatment of multidrug-resistant Staphylococcus-infected orthopedic implants with high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole).

We examined the effectiveness and safety of high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole) for the treatment of orthopedic implants infected with multidrug-resistant Staphylococcus species. The prospective study was conducted between 1989 and 1997 in a university medical center with ambulatory-care services. Patients eligible for the study consisted of those from whom multidrug-resistant Staphylococcus spp. organisms susceptible only to glycopeptides and co-trimoxazole were isolated from their orthopedic implants and for whom there was no contraindication to the treatment. All patients were treated orally with high-dose co-trimoxazole (trimethoprim, 20 mg/kg of body weight/day; sulfamethoxazole, 100 mg/kg/day). Patients with prosthetic hip infections were treated for 6 months, with removal of any unstable prosthesis after 5 months of treatment; patients with prosthetic knee infections were treated for 9 months, with removal of any unstable prosthesis after 6 months of treatment; and patients with infected osteosynthetic devices were treated for 6 months, with removal of the device after 3 months of treatment, if necessary. Monthly clinical evaluations were conducted until the completion of the treatment, and follow-up examinations were conducted regularly for up to 6 years. The overall treatment success rate was 66.7% (26 of 39 patients), with success rates of 62.5% for patients with prosthetic knee infections, 50% for those with prosthetic hip infections, and 78.9% for those with other device infections. Seventeen of the 28 (60.7%) patients who did not have any orthopedic material removed were cured. Eight patients stopped the treatment because of side effects, and one patient was not compliant. In three patients treatment failed because of the appearance of a resistant bacterium. Long-term oral ambulatory treatment with co-trimoxazole appears to be an effective alternative to the conventional medicosurgical treatment of chronic multidrug-resistant Staphylococcus-infected orthopedic implants which includes long-term intravenous antibiotic therapy combined with surgical debridement and removal of foreign material or its subsequent one- or two-stage replacement.

Administration, Oral↗

Staphylococcus epidermidis infections.

Staphylococcus epidermidis, an organism routinely found on the skin and in the hospital environment, has become a primary pathogen in infections associated with prosthetic devices. Because these infections are indolent and often clinically silent, diagnosis and therapy are often difficult. Pathogens are often misidentified as contaminants. Their variable, often resistant antibiotic susceptibility pattern and the uncertain correlation of in-vitro beta-lactam sensitivity testing with therapeutic efficacy make selection of an effective antibiotic regimen difficult. Vancomycin combined with rifampin, gentamicin, or both, is recommended for empiric therapy of these infections. Usually, removal of the prosthetic device is also necessary and may contribute equally to a successful therapeutic outcome.

Anti-Bacterial Agents↗

Community-acquired methicillin-resistant Staphylococcus aureus infections.

Staphylococcus aureus causes a variety of minor diseases but also is responsible for staphylococcal pneumonia and sepsis, both of which can be fatal. It is thought to be responsible for many of the pneumonia deaths associated with the influenza pandemics of the 20th century. The introduction of penicillin in the 1940s greatly improved the prognosis for patients with severe staphylococcal infections. However, after a few years of clinical use, most staphylococcal strains were able to hydrolyze penicillin by producing b-lactamases, making penicillin a useless antibiotic to treat staphylococcal infections caused by b-lactamase-producing S aureus. Methicillin, a semisynthetic penicillin introduced in 1959, was specifically designed to be resistant to b-lactamase degradation, but resistance developed soon after its introduction into clinical practice. Methicillin-resistant S aureus (MRSA) was first reported in the United Kingdom in 1961, followed by reports from other European countries, Japan, and Australia. The first reported case of MRSA in the United States was in 1968. Currently, MRSA is an important pathogen in nosocomial infections and is a problem in hospitals worldwide, and it is increasingly recovered from nursing home residents with established risk factors. More recently, community acquired MRSA infections have been documented among healthy individuals with no recognizable risk factors, and it seems clear that community-acquired MRSA (CA-MRSA) strains are epidemiologically and clonally unrelated to hospital-acquired strains. This review focuses on the epidemiology, clinical significance, and virulence markers of CA-MRSA infections.

Anti-Bacterial Agents↗

Use of antimicrobial susceptibility testing for epidemiology and the selection of oral, parenteral and topical regimens for control of CAPD-associated Staphylococcus aureus infection.

Staphylococcus aureus is an important cause of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Using standard broth microdilution and disk diffusion methodology, we evaluated the in vitro activity of selected antimicrobial agents against S. aureus strains isolated from CAPD patients to assess candidate regimens for 1) topical agent control of colonization, 2) oral chemotherapy of CAPD infectious complications, and 3) parenteral treatment of serious CAPD-associated staphylococcal infections. A total of 34 isolates (31 patients) of S. aureus were available for testing, including 29 isolates (29 patients) from pericatheter skin, four isolates (four patients) from the nares, and one isolate from an episode of peritonitis. Six of the isolates were oxacillin-resistant (ORSA). The antimicrobial agents tested by broth microdilution included 17 different quinolones, 10 cephalosporins, six glycopeptides, two aminoglycosides, and imipenem. A total of eight potential topical agents, including the antistaphylococcal agent mupirocin, were tested by disk diffusion. All of the quinolones, with the exception of nalidixic acid (MIC90 greater than 16 micrograms/ml), had excellent activity against both ORSA and oxacillin-susceptible S. aureus (OSSA) with the most active agent being WIN57273 (MIC90 less than or equal to 0.015 microgram/ml). Imipenem and the cephalosporins, with the exception of cefixime, ceftazidime, and E-1040, possessed good activity against OSSA. None of the beta-lactam agents tested were active against ORSA. Likewise, the aminoglycosides, amikacin and gentamicin, exhibited good activity against OSSA strains but no activity against ORSA strains. All glycopeptides tested demonstrated excellent activity against ORSA strains. Of the topical antimicrobial agents tested only bacitracin, mupirocin, and nitrofurantoin were active against all OSSA and ORSA strains tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Pneumonia due to Staphylococcus aureus infection.

Staphylococcus aureus is the second most common infectious agent of pneumonia in the ICU. The virulence of this organism is highlighted by toxins and enzymes that result in severe damage to lung tissue. Clinical features fail to distinguish Staphylococcus aureus pneumonias from other pathogens, and clinical diagnosis has the same limitations that beset other bacterial causes of pneumonia. Effective therapy is dictated by carefully performed susceptibility testing. First-line therapy is with a beta-lactam agent. If BRSA is detected or beta-lactam intolerance occurs, vancomycin should be administered. Despite agents active in vitro, the mortality of this disease remains high, especially if spread through hematogenous routes.

Anti-Bacterial Agents↗

Adherence measured by microtiter assay as a virulence marker for Staphylococcus epidermidis infections.

Staphylococcus epidermidis strains isolated from clinical sources showed a wide range of abilities to adhere to glass and plastic materials. The degree of adherence depended on a number of factors, most notably, the composition of the growth medium. Adherence was enhanced by the addition of glucose or oleic acid to the growth medium and inhibited by serum. We have demonstrated a statistically significant association between the quantitative assessment of adherence to polystyrene tissue culture plates and clinical relevance. No such association was found when adherence was assessed by the qualitative adherence assay. Possible new approaches for assessing the clinical relevance of coagulase-negative staphylococcal isolates are discussed.

Bacterial Adhesion↗

[Immunomodulating action of hyaluronic acid and its hydrolysis products in health and in Staphylococcus infection].

Potassium hyaluronate was found to suppress the development of a humoral response and delayed hypersensitivity, while hyaluronidase and the incubate of potassium hyaluronate and hyaluronidase enhanced the manifestations of the humoral response and delayed hypersensitivity. The suppressive effect of potassium hyaluronate was mediated by light erythrocytes, whereas the stimulating effect of hyaluronidase the incubates of potassium hyaluronate and hyaluronidase was mediated by heavy erythrocytes. In Staphylococcus infection, hyaluronidase and the incubates of potassium hyaluronate and hyaluronidase enhanced the development of a humoral response and failed to affect the manifestations of delayed hypersensitivity.

Adjuvants, Immunologic↗

Antibiotic-resistant staphylococcus infections.

Strains of antibiotic-resistant staphylococci that develop in a hospital are becoming increasingly important as a cause of untoward complications of hospitalization. The hospital environment and hospital personnel present the chief reservoir of antibiotic-resistant strains; and they, as well as patients discharged after hospital stay, may represent the greatest source of antibiotic-resistant strains found in the community at large.Cross infection appears to be thwarted by rigid adherence to antiseptic techniques.

Anti-Bacterial Agents↗

Protective effects of human milk in experimental staphylococcus infection.

Mice were given human milk and sublethal doses of virulent Staphylococcus aureus subcutaneously on 7 to 14 consecutive days. When mice of this group and mice of control groups were later challenged through intraperitoneal injection of a lethal dose of the same Staphylococcus aureus, the death rate for the experimental group was found to be much lower than the death rate for the controls.

Animals↗

A novel peptide screened by phage display can mimic TRAP antigen epitope against Staphylococcus aureus infections.

Staphylococcus aureus is a major human pathogen. Pathogenic effects are largely due to production of bacterial toxins, whose synthesis is controlled by an mRNA molecule termed RNAIII. The S. aureus protein called RAP (RNAIII-activating protein) is secreted and activates RNAIII production by inducing the phosphorylation of its target protein TRAP (target of RAP). Antibodies to TRAP have been shown to suppress exotoxin production by S. aureus in vitro, suggesting that TRAP may be a useful vaccine target site. Here we showed that a peptide TA21 was identified by screening a phage display library using anti-TRAP antibodies. Mice vaccinated with Escherichia coli engineered to express TA21 on their surface (FTA21) were protected from S. aureus infections, using sepsis and cellulitis mice models. By sequence analysis, it was found that the TA21 is highly homologous to the C-terminal sequence of TRAP which is conserved among S. aureus and Staphylococcus epidermidis, suggesting that peptide TA21 may be a useful broad vaccine to protect from infection caused by various staphylococcal strains.

Animals↗

Comparative in vitro activities of LY191145, a new glycopeptide, and vancomycin against Staphylococcus aureus and Staphylococcus-infected fibrin clots.

Bactericidal activities of LY191145, an investigational glycopeptide, and vancomycin against Staphylococcus aureus were evaluated. Only LY191145 at a concentration 16-fold greater than the MIC was able to achieve 99.9% killing against methicillin-susceptible S. aureus (ATCC 25923; 8.0 h). Both agents demonstrated 99.9% killing against methicillin-resistant clinical isolate S. aureus MRSA67 over 24 h at concentrations 4-, 8-, and 16-fold greater than the MIC, but bacteria were killed at a more rapid rate by LY191145 (1.63 versus 5.02 h; P < 0.001). Against strain ATCC 25923- and MRSA67-infected fibrin clots, total reductions by LY191145 and vancomycin over 72 h were not statistically significantly different at a concentration 16 times the MIC (1.12 +/- 0.31 and 1.23 +/- 0.13 and 1.40 +/- 0.17 and 1.36 +/- 0.37 CFU/g; respectively). Increasing the drug concentration to 50 times the MIC did not alter the values significantly, and there was no statistically significant difference between the two agents. Overall, LY191145 exhibited more rapid bactericidal activity than vancomycin against S. aureus, and a concentration 16-fold greater than the MIC appears to be optimal.

Anti-Bacterial Agents↗

Experimental Staphylococcus infection in the hamster cheek pouch: the process of localization.

Small amounts of staphylococcus suspensions were injected into the cheek pouches of hamsters. Within 5 hours, the organisms were recovered from all outlying areas of the pouches, and in the following hours the entire structures showed vasodilation, edema, petechiae, and accumulation of leukocytes in the venules. Leukocytosis also occurred at this time. Between 24 and 48 hours, well defined abscesses developed at the sites of injection, and there was a sharp decrease in the bacteria in all other areas. From the 3rd day onward, organisms were only occasionally recovered from tissue outside the abscesses. At this period of localization, the generalized edema and petechiae also subsided, as did the leukocytosis. Localization of infection was not due to a walling off process, since the bacteria were disseminated through the entire pouches in the 1st few hours, but these organisms diminished rapidly, while those at the original injection sites continued to grow and reproduce for several days. Localization of infection appeared to be due to the inability of the bacteria carried away from the site of injection to reproduce. This in turn may have been due to dilution, to lack of sufficient toxin to produce a necrotic substrate, or to greater accessibility of these organisms to phagocytes.

Animals↗

[Clinico-microbiological profile of urinary Staphylococcus infection in gynecologico-obstetric patients].

The Enterobacteriaceae are the major cause of urinary tract infections (UTI). The Gram-positive Cocci also produce UTI, of these Staphylococcus saprophyticus are the most frequent reported. To know the clinical and microbiological characteristics of the UTI caused by Staphylococcus in the gyneco-obstetric patients, we made a prospective study of the case identified at the Instituto Nacional de Perinatología during the period from January to July 1992. There were 32 cases, 19 cystourethritis, 12 asymptomatic bacteriuria, and one pyelonephritis. Twenty nine of the Staphylococcus isolated were coagulase-negative (SCN), of them Staphylococcus epidermidis was the most regained. The 82.7% of the SCN isolated had a positive slime test. The antimicrobial susceptibility tests showed a low percent of resistance to the majority of the antimicrobial agents proved excepting penicillin and gentamicin.

Adult↗

Intranasal vaccination with a double mutant of staphylococcal enterotoxin C provides protection against Staphylococcus aureus infection.

Staphylococcus aureus expresses a repertoire of factors including staphylococcal exotoxins (SEs), exoenzymes, and numerous cell-associated components that contribute to the pathogenesis of disease. We constructed and expressed a nontoxic double mutant SEC (dmSEC), devoid of superantigenic activity, and investigated the ability of intranasal vaccination with dmSEC plus cholera toxin (CT) adjuvant to protect mice against S. aureus infection. Mice were vaccinated with dmSEC and inoculated with a viable S. aureus clinical isolate strain. The survival rate in the immunized mice was higher, and bacterial counts in the organs were significantly lower than those in the control group. Intranasal vaccination with dmSEC induced the production of SEC-specific antibodies such as IgG1, IgG2b and IgA. dmSEC-vaccinated mice elicited significantly higher titers of interleukin-4 (IL-4) and IL-10, and lower levels of interferon-gamma (IFN-gamma) after challenge with S. aureus compared with the control group. Furthermore, the sera from dmSEC-immunized mice significantly inhibited IFN-gamma and tumor necrosis factor-alpha production in vitro. These results indicate that intranasal vaccination with dmSEC devoid of superantigenic properties induces systemic immune responses and provides protection against S. aureus infection.

Administration, Intranasal↗

Identifying high risk patients for Staphylococcus aureus infections: skin and soft tissue infections.

Staphylococcus aureus is the causative organism for many skin and soft tissue (SST) infections. Some SST infections have severe systemic complications, such as bacteraemia and sepsis. S. aureus is the cause of 75% of primary pyodermas. Pre-existing conditions, like tissue injury (ulcers, wounds) or tissue inflammation (exudative dermatitis), and also underlying disorders (such as poorly controlled insulin-dependent diabetes mellitus or cancer) are some of the risk factors for secondary infection with S. aureus. In S. aureus-infected primary skin disorders (impetigo, recurrent eczema), 2% mupirocin ointment has proved effective in several clinical trials. S. aureus is responsible for 25% of all burn-wound infections, and burn units could be the point of entry and source of spread of methicillin-resistant S. aureus infection outbreaks. Mupirocin (2% ointment) has also proven effective for topical treatment of these infections. Pressure sores develop in 6% of all patients admitted to acute and chronic health care institutions. An average of three aerobic species (including S. aureus) plus one anaerobic species are isolated when infected. Infectious complications are responsible for 60-80% of all intravenous drug user (IVDU) hospital admissions, 5-20% being due to S. aureus infective endocarditis (IE). The origin of IE in IVDUs is probably the skin. Data from a Collaborative Spanish Study of IVDU infectious complications (including more than 10,000 episodes) are discussed.

Burns↗

Drosophila melanogaster as a model host for Staphylococcus aureus infection.

Staphylococcus aureus is an important pathogen of humans, causing a range of superficial and potentially life-threatening diseases. Infection of the fruit fly Drosophila melanogaster with S. aureus results in systemic infection followed by death. Screening of defined S. aureus mutants for components important in pathogenesis identified perR and pheP, with fly death up to threefold slower after infection with the respective mutants compared to the wild-type. Infection of D. melanogaster with reporter gene fusion strains demonstrated the in vivo expression levels of the accessory gene regulator, agr, alpha-toxin, hla, and a manganese transporter, mntA. The use of the green fluorescent protein as a reporter under the control of the agr promoter (P3) showed S. aureus microcolony formation in vivo. The disease model also allowed the effect of antibiotic treatment on the flies to be determined. D. melanogaster is a genetically tractable model host for high-throughput analysis of S. aureus virulence determinants.

Amino Acid Transport Systems, Neutral↗