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[The production of the tumor necrosis factor in an experimental staphylococcal infection].

The paper deals with the study of production of tumour necrosis factor (TNF), the key mediator of inflammation and immune responses of the organism, under experimental and staphylococcus infection (Staphylococcus aureus, st. 209) on mice of C57B16 line. It is established that staphylococcus infection of animals lead to TNF induction. Dynamics of this cytokinin synthesis by peritoneal macrophages and splenocytes under the infection of mice with S. aureus in different doses differed in time and as to absolute values. In animals infected by staphylococcus in a dose of LD30 the TNF production was high as compared to the control for 72 h after the infection and was normalized on the 4-6th day of the experiment. When using staphylococcus in a dose of LD50, spontaneous production of this cytokinin was higher than that in the control for the whole period of observation.

Animals↗

Imipenem-cilastatin in the treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections.

Imipenem-cilastatin was evaluated for efficacy and toxicity as an antistaphylococcal agent in 23 patients; 11 of these patients were infected with methicillin-resistant Staphylococcus aureus (MRSA), and 12 were infected with methicillin-susceptible S. aureus (MSSA). There were 15 soft tissue, 5 endovascular, and 3 skeletal infections and a total of nine patients with bacteremia. As determined by in vitro susceptibility testing, the MICs for 90% of the MRSA and MSSA isolates tested were 6.25 and 0.39 micrograms/ml, respectively. Two MRSA isolates were resistant to a concentration of greater than 16 micrograms/ml. When 11 MRSA isolates and 7 MSSA isolates were incubated for 48 h the MICs for 90% of the isolates increased to greater than 50 micrograms/ml for the MRSA isolates and 6.25 micrograms/ml for the MSSA isolates. Three S. aureus isolates emerged resistant. Ten of 11 (91%) MRSA infections and 11 of 12 (92%) MSSA infections were clinically cured. Adverse reactions occurred in 25% of the imipenemcilastatin-treated patients. These reactions included gastrointestinal intolerance (7% of the patients), rash or pruritus (6%), eosinophilia (6%), thrombocytosis (4%), and a positive, direct Coomb test without hemolysis (3%). One of the two patients for whom therapy was discontinued because of gastrointestinal intolerance had antibiotic-associated colitis. Imipenem appears to be an effective antistaphylococcal agent against both MRSA and MSSA infections.

Adult↗

Knee joint infections with Staphylococcus aureus and Micrococcus species.

In rabbit knees 600 Staphylococcus aureus organisms produced progressive infection in 50 per cent of the knees injected, whereas 5.3 times 10-7 Micrococcus species caused only transient colonization of the joints. Methicillin, cephacetrile, and clindamycin administered before injection of the staphylococci gave protection. Stainless-steel particles in the knee did not increase susceptibility to infection from injected micrococci but did make established micrococcal infections more persistent. Knees containing steel debris failed to become infected during prolonged staphylococcal bacteremia. Injected autologous blood, either fresh or three days old, did not increase susceptibility to infection. Large doses of steroids, given systemically or intraarticularly, decreased resistance to micrococcal infection and increased the destruction caused by infection due to this organism.

Animals↗

Preoperative use of mupirocin for the prevention of healthcare-associated Staphylococcus aureus infections: a cost-effectiveness analysis.

OBJECTIVE: Staphylococcus aureus is the most common cause of healthcare-associated infections. Intranasal mupirocin treatment probably decreases S. aureus infections among colonized surgical patients. Using cost-effectiveness analysis, we evaluated the cost-effectiveness of preoperative use of mupirocin for the prevention of healthcare-associated S. aureus infections. METHODS: Three strategies were compared: (1) screen with nasal culture and give treatment to carriers, (2) give treatment to all patients without screening, and (3) neither screen nor treat. A societal perspective was taken. Adverse outcomes included bloodstream infection, pneumonia, surgical site infection, death due to underlying illness or infection, readmission, and the need for home health care. Data inputs were obtained from an extensive MEDLINE review and from publicly available government data sources. The following base-case data inputs (and ranges) for sensitivity analysis were used: rate of S. aureus carriage, 23.1% (19%-55%); efficacy of mupirocin treatment, 51% (8%-75%); mupirocin treatment cost, 48.36 US Dollars (24.18-57.74 US Dollars); and hospital costs of bloodstream infection, 25,128 US Dollars (6,194-40,211 US Dollars), pneumonia, 18,366 US Dollars (5,574-28,952 US Dollars), and surgical site infection 16,256 US Dollars (5,119-22,553 US Dollars). Widespread use of mupirocin has been associated with high levels of mupirocin resistance; therefore, a broad range of estimates for efficacy was tested in the sensitivity analysis. PATIENTS: The target population included patients undergoing nonemergent surgery requiring postoperative hospitalization. RESULTS: Both the screen-and-treat and treat-all strategies were cost saving, saving 102 US Dollars per patient screened and 88 US Dollars per patient treated, respectively. In 1-way sensitivity analyses, the model was robust with respect to all data inputs except for the efficacy of mupirocin treatment. If the efficacy is less than 16.1%, then the screen-and-treat strategy is cost incurring. A treat-all strategy was more cost saving if the rate of S. aureus carriage was greater than 42.7%, the mupirocin cost was less than 29.87 US Dollars, or nursing compensation was greater than 64.21 US Dollars per hour. CONCLUSION: Administration of mupirocin before surgery is cost saving, primarily because healthcare-associated infections are very expensive. The level of mupirocin efficacy is critical to the cost-effectiveness of this intervention.

Anti-Bacterial Agents↗

Comparison of phage typing, plasmid mapping, and antibiotic resistance patterns as epidemiologic markers in a nosocomial outbreak of methicillin-resistant Staphylococcus aureus infections.

Isolates of methicillin-resistant Staphylococcus aureus obtained during a nosocomial outbreak were analyzed by phage typing, plasmid mapping, and antibiotic susceptibility patterns for epidemiologic markers. Antibiotic susceptibility patterns were of limited use epidemiologically because of multiple resistance and similarity of the strains. Phage typing demonstrated that the outbreak consisted of multiple introductions of MRSA organisms into the hospital from the community and from other hospitals, and of circulation of one predominant phage type, 6/47/54/81. Plasmid mapping further subdivided the organisms of this phage type into two different groups, one of which carried two particular plasmids. Organisms carrying these plasmids were significantly more resistant to methicillin and cephalosporins and were isolated from patients who had received prior antibiotic treatment.

Anti-Bacterial Agents↗

Staphylococcus epidermidis endocarditis and Staphylococcus epidermidis infection in an intensive care unit.

Staphylococcus epidermidis are the most common agents of prosthetic valve endocarditis (PVE). S. epidermidis isolated from the blood stream of patients with PVE are almost invariably multiple resistant to antibiotics. Antibiotic treatment alone gives unsatisfactory results and carries a mortality rate of 70-80%. That is why early surgical treatment is recommended. S. epidermidis is a less common cause of endocarditis in non-surgical patients, accounting for approximately 5% of the cases, which are mostly patients with pre-existent valvular heart disease. Generally, isolates from the latter patients are sensitive to most antibiotics, and the mortality rate is considerably lower. Recently coagulase-negative staphylococci have emerged as causative agents of septicaemia in patients hospitalized in intensive care units. Especially premature infants of very low-birth weight (less than 1500 g) receiving parenteral nutrition appear to carry a high risk of acquiring this kind of septicaemia. Although the staphylococci isolated from the blood of these patients are the same as in patients with PVE, generally multiple resistant to antibiotics, prognosis is far better than in cases of PVE. In our study carried out in a neonatal intensive care unit, two risk factors for coagulase-negative staphylococcal septicaemia were identified. First, nearly 20% of parenteral nutrition fluids used in the unit were found to be contaminated with coagulase-negative staphylococci, and a significant association was established between septicaemia and the infusion of contaminated fluids. Moreover, opsonization of staphylococci in infant serum proved to be severely deficient. Since host defence to staphylococci is dependent on optimal opsonization of these microorganisms, this defence may be severely compromised in the premature neonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Platelet abnormalities in a dog suffering from gangrenous mastitis by Staphylococcus aureus infection.

Severe gangrenous mastitis due to Staphylococcus aureus infection was diagnosed in a 7 year-old intact female beagle which was presented with swelling of mammary glands after dystocia. Leukocytosis (25,200-48,600/microliters), decreased platelets (107,000-179,000/microliters), and abnormal platelet pattern continued during the critical condition. Consistent with platelet pattern, large platelets were observed in the blood smear. The number of leukocytes and platelets rapidly returned to normal during treatment, and the platelet pattern was also restored. The number and pattern of platelet may provide a clue for the evaluation of the clinical condition and/or severity of the lesions in the dog with mastitis.

Animals↗

Cost of nosocomial infection: relative contributions of laboratory, antibiotic, and per diem costs in serious Staphylococcus aureus infections.

This study reports an analysis of the relative importance of laboratory antibiotic, and per diem costs of caring for 58 patients with serious Staphylococcus aureus nosocomial infections. Laboratory costs accounted for 2%, antibiotics for 21%, and per diem costs for 77% of total infection-related costs. Only 45% of patients were hospitalized for additional days specifically because of infection, but these patients stayed an average of 18 extra days. Nosocomial infections with S. aureus resistant to penicillinase-resistant penicillins (PRP) were more frequently associated with additional infection-related days of hospitalization than were PRP-susceptible infections. The cost of PRP-resistant infections was also significantly greater than PRP-susceptible infections, primarily because of the costs of additional days of hospitalization. Rational strategies to control costs of nosocomial infection should focus on two approaches: (1) prevention and (2) reduction of acute hospital days attributable to infections.

Adult↗

Methicillin-resistant Staphylococcus aureus infection in a cardiac surgical unit.

BACKGROUND: Increased antibiotic resistance of common bacteria is attributed in part to the widespread use of various antibiotic agents. Prophylactic and therapeutic antibiotic treatments are routinely used in cardiac surgical units, and it is no surprise that methicillin-resistant Staphylococcus aureus infection is becoming a major cause of surgical infections in cardiac patients. METHODS: We reviewed our experience with patients who underwent cardiac surgery and experienced infection caused by methicillin-resistant Staphylococcus aureus. Between 1992 and 2000 at the Montreal Heart Institute, 39 patients had methicillin-resistant Staphylococcus aureus surgical infections, and 13,199 patients underwent cardiac surgery. The yearly incidence of methicillin-resistant Staphylococcus aureus infection, the relative risk of acute mediastinitis and of superficial wound infections or other types of methicillin-resistant Staphylococcus aureus infection episodes, and the effect of preventive measures were analyzed. RESULTS: The annual incidence of methicillin-resistant Staphylococcus aureus acute mediastinitis decreased from 0.37% (5/1321) of cardiac patients in 1992 and 0.44% (6/1355) in 1993 to 0% between 1994 and 1997, 0.13% (2/1528) in 1999, and 0% (0/1700) in 2000. The total incidence of methicillin-resistant Staphylococcus aureus infection, including mediastinitis, superficial and deep sternal and leg wound infection, and all systemic infection episodes ranged from 0.68% of patients in 1992 and 0.96% of patients in 1993 to 0.46% of patients in 1999 and 0.53% of patients in 2000. The relative risk of severe mediastinal methicillin-resistant Staphylococcus aureus infection to all other methicillin-resistant Staphylococcus aureus infection episodes decreased from 1.65 in 1992 to 0.41 in 1999 and 0 in 2000. Beginning in 1993, all patients given a diagnosis methicillin-resistant Staphylococcus aureus infection and all nasal carriers of methicillin-resistant Staphylococcus aureus were strictly isolated on the surgical unit, and vancomycin was used as the prophylactic antibiotic agent for cardiac surgery in these patients. Moreover, since 1998, all patients admitted in the hospital were screened, and nasal carriers were isolated and treated with topical antibiotic ointment. CONCLUSION: Mediastinal and other infections caused by methicillin-resistant Staphylococcus aureus have a significant morbidity in cardiac surgical patients. After an outbreak of methicillin-resistant Staphylococcus aureus mediastinal infections, several preventive measures to control methicillin-resistant Staphylococcus aureus contamination of surgical patients were implemented (nasal screening, preventive isolation, application of mupirocin, prophylaxis with vancomycin and alcohol gels) and were effective in decreasing the incidence of methicillin-resistant Staphylococcus aureus infection and mediastinitis after cardiac surgery.

Acute Disease↗

Widespread emergence of methicillin resistance in community-acquired Staphylococcus aureus infections in Denver.

BACKGROUND: Increasing rates of methicillin resistance among out-patient Staphylococcus aureus infections led us to assess the epidemiology and outcome of a local outbreak. METHODS: A retrospective cohort study of outpatient skin and soft tissue infections due to S aureus in 2003. RESULTS: From 2002 to mid-2004, the percentage of outpatient S aureus isolates resistant to methicillin increased from 6 to 45%. In multivariate analysis, only male sex and age greater than 18 years were associated with methicillin resistance. Methicillin resistance was common (>15%) among isolates from patients in nearly all subgroups evaluated. Pulsed field gel electrophoresis showed isolates related to USA 300, but methicillin-resistant strains had unusually high rates of quinolone resistance. CONCLUSIONS: A single strain of methicillin-resistant S aureus is responsible for the increase in skin infections in outpatients without traditional risk factors for infection with an antibiotic-resistant strain. In areas with high rates of methicillin-resistant S aureus outpatient infections, we recommend non-beta-lactam antibiotics for initial treatment of skin and soft tissue infections.

Adolescent↗

The role of gamma interferon in acquired host resistance against Staphylococcus aureus infection in mice.

We investigated the expression of an acquired host resistance against Staphylococcus aureus infection in mice. When C57BL/6 mice were immunized with viable S. aureus and challenged with S. aureus eight weeks later, the elimination of S. aureus from the spleen and liver was enhanced in the immunized mice compared with the nonimmunized mice. When gamma interferon (IFN-gamma(-/-)) mice were immunized and challenged, the bacterial numbers in the organs of immunized mice were comparable to those in the nonimmunized mice, suggesting that IFN-gamma plays a critical role in an acquired host resistance against S. aureus infection. IFN-gamma(-/-) mice produced the lower level of anti-S. aureus immunoglobulin M (IgM) and IgG2a antibodies compared with C57BL/6 mice. To elucidate the role of IFN-gamma produced during a challenge with S. aureus, a single injection of anti-IFN-gamma monoclonal antibody to mice was carried out 1 h before challenge. An acquired resistance against S. aureus infection was inhibited by injecting with anti-IFN-gamma monoclonal antibody. However, anti-IFN-gamma monoclonal antibody treatment failed to modulate anti-S. aureus IgM, IgG1 or IgG2a responses in these animals. These results demonstrated that IFN-gamma is required for an acquired resistance against S. aureus infection in mice. However, IFN-gamma induced during the challenge failed to affect the secondary antibody responses.

Animals↗

The biological performance of calcium phosphate ceramics in an infected implantation site: I. Biological performance of hydroxyapatite during Staphylococcus aureus infection.

In the present study the biological performance of macroporous and dense hydroxyapatite after implantation in the rat middle ear was evaluated during an induced Staphylococcus aureus middle ear infection. The course of the infection was similar to that in the absence of an implant. Hydroxyapatite was frequently integrated with fibrous ingrowths in the middle ear lumen, originating solely from the infection. Good epithelial covering of the implant with all types of epithelial cells of importance for middle ear defence, was found. Increase of the exudate in the pores due to the infection was relatively small, and most of the exudate was restricted to pores on the implant surface. The bony tissue in the pores was not influenced significantly by the induced infection. Degradation of hydroxyapatite was consistent with earlier results obtained in the non-infected middle ear. The results obtained so far suggest that hydroxyapatite is highly suitable for middle ear implantation.

Animals↗

The pathogenesis of Staphylococcus aureus infection in the diabetic NOD mouse.

Although Staphylococcus aureus is a major pathogen implicated in diabetic foot infections, little is known about the pathogenesis of this disease. A model of S. aureus infection in the hindpaw of nonobese diabetic (NOD) mice was developed. The experimental infection was exacerbated in diabetic mice (blood glucose levels > or =19 mmol/l) compared with nondiabetic mice, and the diabetic animals were unable to clear the infection over a 10-day period. Insulin-mediated control of glycemia in diabetic mice resulted in enhanced clearance of S. aureus from the infected tissue. Diabetic mice showed reduced tissue inflammation in response to bacterial inoculation compared with nondiabetic NOD animals, and this was consistent with the novel finding of significantly decreased tissue levels of the chemokines KC and MIP-2 in diabetic mice. Blood from nondiabetic and diabetic NOD mice killed S. aureus in vitro, whereas the bacteria multiplied in blood from diabetic mice with severe hyperglycemia. The impaired killing of S. aureus by diabetic mice was correlated with a diminished leukocytic respiratory burst in response to S. aureus in blood from diabetic animals. This animal model of hindpaw infection may be useful for the analysis of host defects in innate immunity that contribute to recalcitrant diabetic foot infections.

Animals↗

Oral treatment of Staphylococcus spp. infected orthopaedic implants with fusidic acid or ofloxacin in combination with rifampicin.

Oral therapy of staphylococcal infection of orthopaedic implants with 900 mg/day rifampicin combined with either 1.5 g/day fusidic acid for 5 days followed by 1 g/day thereafter, or 600 mg/day ofloxacin was compared. Patients with an infected hip were treated for 6 months, with removal of any unstable prosthesis after 5 months' treatment and those with an infected knee prosthesis were treated for 9 months, with removal of the prosthesis after 6 months of treatment. Patients with infections of other type of bone implants were treated for 6 months with removal of the implant after 3 months of treatment, if necessary. Cure was defined as the absence of clinical, microbiological and radiological evidence of infection 12 months after completion of treatment. The treatment of 46 of the 52 included in the study was evaluated for safety and that of 42 was assessed for efficacy. Overall treatment was successful for 11 (55%) of 20 patients treated with rifampicin and fusidic acid group and for 11 (50%) of the 22 treated with rifampicin and ofloxacin. Treatment failed in four cases in each treatment group because of persistent infection. One patient given rifampicin and fusidic acid and three patients given rifampicin and ofloxacin failed treatment because of relapse. Superinfection led to failure in the remainder and was due to staphylococci in all but one case in which Acinetobacter calcoaceticus var. anitratus was isolated. There were no side effects related to study treatment. Oral treatment with rifampicin combined with fusidic acid may be a suitable alternative to the combination of rifampicin and ofloxacin for treating implant infections due to Staphylococcus spp. either when the patient is intolerant to quinolones or when the infecting organism is resistant to these drugs.

Administration, Oral↗

Control of a hospital outbreak of methicillin-resistant Staphylococcus aureus infections: value of an isolation unit.

An outbreak of methicillin- and gentamicin-resistant Staphylococcus aureus infections started in a university hospital after a patient, who was not known to be colonized, was admitted. During a 3-month period 15 surgical or geriatric patients and five staff were found to be infected or colonized by the epidemic strain in five surgical/orthopaedic wards, a geriatric ward, the intensive care unit and the isolation unit. Difficulties in controlling the outbreak arose when two patients who initially had negative bacteriological screening results were returned to general wards. Both patients were subsequently shown to be colonized and caused outbreaks which led to the further closure of two general wards. There was strong circumstantial evidence to suggest that physiotherapy staff were involved with the spread of the epidemic strain. Control of the outbreak was achieved by more strict isolation of 'negative' patient contacts as well as colonized/infected patients and increasing the level of staffing on the separate isolation unit.

Cross Infection↗

Clinical and molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus infections among children with risk factors for health care-associated infection: 2001-2003.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has recently emerged as a common cause of infection in children in many parts of the world. The epidemiology of community-acquired MRSA (CA-MRSA) among healthy children has been recently described. However, little is known about CA-MRSA in children with underlying medical conditions. OBJECTIVE: To compare the clinical and molecular epidemiology of CA-MRSA in children with and without risk factors for health care-associated infections (RF-HAI). METHODS: We conducted a 3-year retrospective cohort study of children with CA-MRSA infection. RF-HAI, including hospitalization within the past year, indwelling medical devices or chronic medical condition, were identified by chart review. Genetic relatedness of CA-MRSA strains was assessed by pulsed field gel electrophoresis. Polymerase chain reaction was used to detect Panton-Valentine leukocidin and determine staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) type. RESULTS: We identified 446 episodes of community-acquired S. aureus infections, of which 134 (30%) were caused by MRSA. During the 3-year study period, the proportion of S. aureus infections caused by MRSA rose from 15% (12 of 80) to 40% (93 of 235) (P < 0.001) with the increase noted predominately in children with skin and soft tissue infections. RF-HAI were identified in 56 (42%) patients with CA-MRSA. Among subjects with CA-MRSA, children with RF-HAI were more likely to have had an invasive infection than healthy children (32% versus 5%; P < 0.001). CA-MRSA isolates from children with RF-HAI were similar to those without RF-HAI; all laboratory-retained CA-MRSA isolates harbored the SCCmec type IV cassette, and almost all isolates were susceptible to trimethoprim-sulfamethoxazole and clindamycin. However, pulsed field gel electrophoresis revealed greater molecular diversity among CA-MRSA isolates recovered from children with RF-HAI compared with those from otherwise healthy children (P = 0.001). Additionally CA-MRSA isolates from children with RF-HAI were less likely to contain sequences for Panton-Valentine leukocidin (P < 0.001) and more likely to be resistant to 3 or more classes of antibiotics (P = 0.033). CONCLUSION: CA-MRSA strains recovered from children with RF-HAI were phenotypically similar to those recovered from healthy children The absence of SCCmec type II or III MRSA among children with RF-HAI suggests that CA-MRSA strains might have become endemic within pediatric health care facilities.

Child↗

Methicillin-resistant Staphylococcus aureus infections in ICU patients.

The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in patients admitted to the intensive care unit has dramatically increased in recent years, with an associated increase in morbidity and mortality and the costs of caring for patients with MRSA infections. Although indiscriminate and inappropriate use of antibiotics has contributed to this phenomenon, horizontal transmission of MRSA between patients and health care providers is the principal cause of this observed increase. This article discusses the pathogenesis, epidemiology, treatment, and prevention of MRSA infections in critically ill patients.

Bacteremia↗

Lack of efficacy of mupirocin in the prevention of infections with Staphylococcus aureus in liver transplant recipients and candidates.

BACKGROUND: Infections with Staphylococcus aureus are a significant problem in patients in liver transplant units. An association between prior nasal carriage with and subsequent infections has been documented previously in liver transplant recipients and patients with cirrhosis. However, the role of decolonization with mupirocin applied intranasally for the prevention of S. aureus infections in these patients has not been determined. METHODS: S. aureus nasal carriage was prospectively sought in 70 consecutive liver transplant candidates. Mupirocin two times per day for 5 days was administered to the carriers. Follow-up nasal cultures to document decolonization were performed 5 days after the final application of mupirocin. The primary endpoint was the development of S. aureus infections. RESULTS: Thirty-one of 70 patients (44%) were found to be nasal carriers and 27 of 31 nasal carriers (87%) were successfully decolonized. However, 12 of 27 patients (37%) successfully decolonized became recolonized with S. aureus, and an additional nine patients who were initially noncarriers became newly colonized with S. aureus during the study period. Despite the use of mupirocin, 16 of 70 patients (23%) developed an infection with S. aureus. No isolate was found to be mupirocin resistant. CONCLUSION: Elimination of S. aureus nasal carriage by mupirocin did not prevent S. aureus infections in patients in our liver transplant unit.

Adult↗