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Direct medical costs associated with using vancomycin in methicillin-resistant Staphylococcus aureus infections: an economic model.

OBJECTIVES: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP). RESEARCH DESIGN AND METHODS: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario. MAIN OUTCOME MEASURES: The cost of using vancomycin in the four indications, including and excluding hospital cost. RESULTS: Whereas the drug acquisition price of vancomycin 1g is US dollars 9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to US dollars 29-US dollars 43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP,US dollars 779, US dollars 749, US dollars 2261, and US dollars 768, respectively. Total costs, including hospital length of stay, were for SSTI US dollars 23616, bacteremia US dollars 26446, IE US dollars 48925, and HAP US dollars 22493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications. CONCLUSIONS: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.

Anti-Bacterial Agents↗

Reversible nephrotic syndrome in a patient with amyloid A amyloidosis of the kidney following methicillin-resistant Staphylococcus aureus infection.

A common form of methicillin-resistant Staphylococcus aureus (MRSA) associated glomerulonephritis is either an endocapillary proliferative glomerulonephritis or a crescentic glomerulonephritis. This report describes the development of reversible nephrotic syndrome following MRSA infection in a patient with amyloid A amyloidosis. The patient had been diagnosed as having rheumatoid arthritis for 50 years. Suppurative arthritis due to MRSA became complicated 2 years prior to admission to our hospital. In the meantime, a nonnephrotic-range proteinuria developed. Two weeks before admission, nephrotic syndrome developed. The serum creatinine level remained unchanged throughout the course, but common features characteristic of MRSA-associated glomerulonephritis were observed in this patient, such as elevated serum IgG and IgA levels. A renal biopsy specimen showed glomerular amyloid A amyloidosis of a nodular type, infiltrated mononuclear cells in the mesangium, deposition of IgG, IgA, and C3, and swelling of glomerular endothelial cells. There were no crescentic glomeruli. Following surgical eradication of the MRSA focus in the right knee joint, nephrotic syndrome disappeared. Hence, it was highly possible that MRSA infection induced a reversible nephrotic syndrome by causing reversible injuries to glomerular endothelial cells. The description of this case serves to illustrate the range of MRSA infections that may cause various forms of glomerulonephritides.

Aged↗

A common-source outbreak of Staphylococcus epidermidis infections among patients undergoing cardiac surgery.

A single strain of Staphylococcus epidermidis caused an outbreak of postoperative wound infections and endocarditis during a 6-month period. Infections caused by the epidemic strain developed more frequently in valve surgery patients than in those undergoing coronary artery bypass graft surgery (P = .03) and occurred only in patients operated on by surgeon A. None of 17 members of the cardiac surgery team carried the epidemic strain in their anterior nares, axillae, or inguinal folds. Hand cultures were performed on 8 surgical personnel, and only surgeon A carried the epidemic strain on his hands. Isolates from cardiac surgery patients, bypass pump blood cultures, and the hands of the implicated surgeon all had identical antimicrobial susceptibility patterns, plasmid profiles, and EcoRI restriction endonuclease digest patterns. In the 24 months after control measures were implemented, no infections caused by the epidemic strain occurred among open heart surgery patients. The findings suggest that the common-source outbreak of infections among cardiac surgery patients was due to carriage of a strain S. epidermidis on the hands of a cardiac surgeon.

Adult↗

Management of staphylococcal and streptococcal infections.

Staphylococcus and streptococcus are bacteria commonly found on the skin and in the mucous membrane. These bacteria are frequently associated with mild cutaneous infections but may invade to cause deeper infections including necrotizing soft-tissue infections, sepsis with or without metastatic lesions, and immunologic or toxin associated sequelae. Early recognition and timely intervention are the hallmarks of appropriate management. Initial empiric therapy should be directed towards a broad spectrum of pathogens that include staphylococcus and streptococcus.

Anti-Bacterial Agents↗

Clinical and economic effects of mupirocin calcium on preventing Staphylococcus aureus infection in hemodialysis patients: a decision analysis.

This study was performed to determine the clinical and economic consequences of alternative strategies of preventing Staphylococcus aureus infection in chronic hemodialysis patients by use of intranasal mupirocin calcium to clear nasal carriage of S aureus. Decision analysis evaluated clinical outcomes and cost-effectiveness of three likely management strategies to address S aureus nasal carriage and prevent subsequent infection in chronic ambulatory hemodialysis patients: (1) screen for S aureus nasal carriage every 3 months and treat those with a positive test result with mupirocin calcium; (2) treat all patients weekly with mupirocin calcium; or (3) no prevention strategy, treat infection only. Rates of nasal carriage of S aureus, S aureus infection rates, proportion of infections attributable to nasal carriage, efficacy of mupirocin, natural history of infection, and patient management strategies were derived from the published literature and supplemented by a panel of experts. Actual payments for medical services were obtained from Medicare parts A and B. Incremental cost-effectiveness was calculated from the perspective of Medicare and subjected to sensitivity analyses. Assuming that 75% of S aureus infections are attributable to nasal carriage in hemodialysis patients, eliminating nasal carriage of S aureus with mupirocin calcium (with or without screening) markedly reduces the number of infections (45% to 55%) and also reduces health care expenditures relative to treating infections when they occur. Annual savings to Medicare are $784,000 to $1,117,000 per 1,000 hemodialysis patients, depending on the prevention strategy. Preventing S aureus infection by eradicating nasal carriage in chronic hemodialysis patients reduces morbidity while simultaneously reducing medical care costs. The decision to eliminate nasal carriage on a regular basis or use a screening test to guide antibiotic therapy is dependent on the tradeoff between improved short-term clinical and cost benefits and the potential for bacterial resistance that may arise from widespread use of mupirocin calcium.

Administration, Intranasal↗

IgG2 deficiency in methicillin-resistant Staphylococcus aureus infections after esophageal surgery.

We previously reported the selective development of methicillin-resistant Staphylococcus aureus (MRSA) infections following esophageal surgery in patients with a reduced ability to produce anti-pneumococcal polysaccharide (PPS) IgG. Since the response to the PPS vaccine is correlated to the serum IgG2 levels, we measured IgG2 in the same series of esophageal cancer patients. IgG subclasses were determined in 21 patients, 8 of whom developed MRSA infections. IgG2 was thus found to be significantly lower (P < 0.01) in patients with MRSA infections (453 mg/dl) than in those without such infections (666 mg/dl). There was also a significantly positive correlation (r = 0.61) between anti-PPS IgG and serum IgG2. Therefore, the preoperative measurement of serum IgG2 is considered to be useful in detecting patients who are at risk for developing an MRSA infection after esophageal surgery.

Esophageal Neoplasms↗

A case of methicillin-resistant Staphylococcus aureus infection following bile duct stenting.

AIM: To present a case of methicillin-resistant Staphylococcus aureus (MRSA) infection following bile duct stenting in a patient with malignant biliary obstruction. METHODS: A 78-year-old male patient was admitted to a community hospital with progredient painless jaundice lasting over two weeks, weight loss and sweating at night. Whether a stent should be implanted pre-operatively in jaundiced patients or whether these patients should directly undergo surgical resection, was discussed. RESULTS: ERC and a biopsy from the papilla of Vater revealed an adenocarcinoma. In addition, a 7-Ch plastic stent was placed into the common bile duct. Persistent abdominal pain, increasing jaundice, weakness and indigestion led to the transfer of the patient to our hospital. A pylorus-preserving pancreatoduodenectomy was performed. Intraoperatively, bile leaked out of the transected choledochus and the stent was found to be dislocated in the duodenum. A smear of the bile revealed an infection with MRSA, leading to post-operative isolation of the patient. CONCLUSION: As biliary stents can cause severe infection of the bile, the need for pre-operative placement of biliary stents should be carefully evaluated in each individual case.

Adenocarcinoma↗

Co-infection of Staphylococcus aureus or Haemophilus paragallinarum exacerbates H9N2 influenza A virus infection in chickens.

H9N2 influenza viruses are frequently isolated from chicken meat and bone marrow imported from China to Japan since 2001. These isolates were experimentally inoculated into specific pathogen-free chickens intranasally. Viruses were recovered from the meat and bone marrow of birds showing no overt signs. On the other hand, chickens co-infected with H9N2 virus and either Staphylococcus aureus or Haemophilus paragallinarum showed clinical signs severer than those shown by birds infected only with the virus alone or each of the bacteria alone. In addition, H9N2 viruses were more efficiently recovered from the chickens co-infected with S. aureus or H. paragallinarum than those from the birds infected with only the virus. The present results indicate that co-infection of H9N2 influenza virus with S. aureus or H. paragallinarum enhances the replication of the virus in chickens, resulting in exacerbation of the H9N2 virus infection.

Animals↗

Clinical and economic analysis of methicillin-susceptible and -resistant Staphylococcus aureus infections.

BACKGROUND: The rate of methicillin-resistant Staphylococcus aureus (MRSA) has increased significantly over the last decade. Previous cohort studies of patients with MRSA bacteremia have reported higher mortality rates, increased morbidity, longer hospital length of stay (LOS), and higher costs compared with patients with methicillin-susceptible S. aureus (MSSA) bacteremia. The clinical and economic impact of MRSA involving other sites of infection has not been well characterized. OBJECTIVE: To determine the clinical and economic implications of MRSA compared with MSSA infections across a variety of infection sites and severity of illnesses. METHODS: A retrospective, case-control analysis comparing differences in clinical and economic outcomes of patients with MRSA and MSSA infections was conducted at an academic medical center. Case patients with MRSA infection were matched (1:1 ratio) to control patients with MSSA infection according to age, site of infection, and type of care. RESULTS: Thirty-six matched pairs of patients with S. aureus infection were identified. Baseline characteristics of patients with MSSA and MRSA infection were similar. Patients with MRSA infections had a trend toward longer hospital LOS (15.5 vs 11 days; p = 0.05) and longer antibiotic-related LOS (10 vs 7 days; p = 0.003). Median hospital cost associated with treatment of patients with MRSA infections was higher compared with patients with MSSA infections ($16,575 vs $12,862; p = 0.11); however, this difference was not statistically significant. Treatment failure was common in patients with MRSA infection. Among patients with MSSA infections, treatment failure was associated with vancomycin use. CONCLUSIONS: Patients with MRSA infections had worse clinical and economic outcomes compared with patients with MSSA infections.

Academic Medical Centers↗

[Methicillin-resistant Staphylococcus aureus infection and its treatment in burned patients].

Burn wound and systemic infections caused by methicillin-resistant Staphylococcus aureus (MRSA) were analysed in 95 patients. Results showed that both 95 (92.2%) out of 103 strains of Staphylococcus aureus isolated from burn wound and all 17 strains from blood were MRSA. Wound MRSA infection could be found in patients with variety of severity and in any kind of wound, while systemic MRSA infection was often occurred in extensive burn patients. The isolated MRSA were most resistant to cephalosporins and sensitive to vancomycin. In order to control wound MRSA infection, Lysostaphin which is active against these organisms could be used as a topical antimicrobial.

Administration, Cutaneous↗

Immunization with glutathione S-transferase and mutant toxic shock syndrome toxin 1 fusion protein protects against Staphylococcus aureus infection.

To investigate whether immunization with glutathione S-transferase (GST) and mutant toxic shock syndrome toxin 1 (mTSST-1) fusion protein can protect against Staphylococcus aureus infection, we purified a non-toxic mutant GST-mTSST-1 fusion protein. Mice were immunized with the GST-mTSST-1 plus alum adjuvant and then challenged with viable S. aureus. The results showed that the survival rate of GST-mTSST-1-immunized group was higher and the bacteria counts in the organs were significantly lower than those of the non-immunized mice. Immunization with GST-mTSST-1 induced strongly the production of TSST-1 specific antibodies, especially immunoglobulin G1 and immunoglobulin G2b. Furthermore, the serum samples from GST-mTSST-1-immunized mice also significantly inhibited interferon-gamma and tumor necrosis factor-alpha production from murine spleen cells by TSST-1. These results suggest that vaccination with GST-mTSST-1 provides protection against S. aureus infection and that the protection might be mediated by TSST-1-neutralizing antibody.

Adjuvants, Immunologic↗

New methods of control against postoperative methicillin-resistant Staphylococcus aureus infection.

The incidence of postoperative infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in Japan has been increasing dramatically. In March 1990, we assigned special doctors in infection control (infection control doctor, ICD), and defined comprehensive controls against MRSA infection. A total of 3536 cases of digestive tract surgery performed at our department were studied during the period between September 1987 and August 1997. We changed the use of antibiotics to prevent postoperative infection. Cefazolin (CEZ) was employed for surgery of the upper digestive tract, including esophagus, stomach, duodenum, and gallbladder. Cefotiam (CTM) was employed for surgery of the lower digestive tract, liver, and pancreas. In esophageal resection, the tracheal tube was extracted during the early postoperative period, and for cervical esophagogastroanastomosis, the autosuture was changed to layer-to-layer anastomosis. We have achieved successful control of postoperative MRSA infection, the incidence having decreased to 0.3% (9/2703). In conclusion, our methods of control against postoperative MRSA infection implies that comprehensive measures of prevention, including the reviewed specification and usage of antibiotics and operation management, have been well implemented. This value is the lowest and the first of any domestic hospital or institute in Japan, suggesting a continued and significant decrease.

Cephalosporins↗

Inflammatory cell infiltration as an indicator of Staphylococcus aureus infection and therapeutic efficacy in experimental mouse mastitis.

Staphylococcus aureus intramammary colonization of the mouse mammary gland induces migration of polymorphonuclear neutrophils (PMNs) similar to that observed during bovine mastitis. In the present study, a method combining acridine orange staining, fluorescence microscopy and computer-assisted image analysis has been developed to quantitate PMN infiltration in a mouse model of mastitis. This was carried out using paraffin embedded sections, and using this method, we showed that the presence of PMNs increased with the number of bacteria present in tissues. Nearly 400 and 1100 times more PMNs were counted in the mammary gland tissue after 12 and 24 h of infection, respectively, compared to mice infected for 6 h. Treatment with the antibiotic cephapirin at 10 or 25 mg/kg reduced PMN infiltration by 71 and 85%, respectively. In conclusion, this method can be used to quantitate PMN infiltration as a marker of inflammation and bacterial burden in infected tissue sections.

Acridine Orange↗

[Relation of intrahospital morbidity from staphylococcal infections to some properties of hospital strains].

Analysis of staphylococcus infection morbidity in a large obstetrical hospital for 5 years offered a possibility of establishing an association between the severity of the course of staphylococcus infections in patients, the bacteriophage type of the causative agent and its resistance to antibiotics. The qualitative changes in morbidity in the direction of the prevalence of minor forms and mild course ocurred in parallel with the changes of the leading bacteriophage type from the epidemic 75/77 and 80/81 to the nonepidemic bacteriophage types of the III bacteriophage group and the changes of the antibiograms of the causative agents in the direction of an increase in the number of strains sensitive to antibiotics. Since the severity of the course of staphylococcus infection characterized the pathogenicity of the strain of the causative agent a conclusion could be drawn on the association between the sign of virulence and determinants of the medicinal resistance and definite prophages in the hospital strains of staphylococcus.

Adult↗

Impact of methicillin-resistant Staphylococcus aureus infections on key health economic outcomes: does reducing the length of hospital stay matter?

The clinical and economic impact of methicillin-resistant staphylococcal infections on the patient, the hospital and the community is significant and continues to increase. Methicillin-resistant Staphylococcus aureus infections, in particular, represent a substantial burden of resistant infections in the hospital. As such, it is important to analyse the cost parameters associated with an episode of infection. Key determinants of the total cost of an episode of infection include fixed costs and hotel costs; the contribution of antimicrobial therapy, including drug acquisition and delivery costs, is comparatively marginal. Therefore, decreasing the hospital length of stay by promoting earlier hospital discharge will significantly reduce overall costs and, in effect, increase the efficiency and cost-effectiveness of the hospital. Linezolid, the first marketed agent of a new class of oxazolidinone antibiotics, is effective in the treatment of serious Gram-positive infections. Its availability in both intravenous (iv) and oral formulations (the latter of which is 100% bioavailable) facilitates early discharge from hospital. Hospitalized patients with methicillin-resistant staphylococcal infections who were treated with either linezolid or vancomycin demonstrated no significant differences in clinical outcome or mortality. However, compared with vancomycin, administration of linezolid reduced the duration of iv therapy and increased the chance of being discharged during the first week of hospitalization. These effects were most pronounced in the subset of patients with skin and soft tissue infections. Knowledge of these data may influence prescribing practices at the individual and organizational levels and, in turn, reduce the economic burden associated with MRSS infections.

Acetamides↗

Methicillin-resistant Staphylococcus aureus infections in acute rhinosinusitis.

OBJECTIVE/HYPOTHESIS: Methicillin-resistant Staphylococcus aureus (MRSA) has recently become a serious problem in various fields of medicine. However, it has rarely been studied in acute rhinosinusitis. The aim of this study was to identify the clinical manifestations and treatment outcome of community-acquired methicillin-resistant S. aureus in acute rhinosinusitis. STUDY DESIGN: This was a prospectively collected case series. METHODS: Since 2000, we have launched a prospective long-term study for bacteriology, drug susceptibility, and their changing trend in acute rhinosinusitis. Patients with the diagnosis of acute rhinosinusitis were enrolled from October 2000 through March 2003. Their middle meatus discharge was taken for aerobic culture. Antibiotic sensitivity test was performed for each isolate. RESULTS: A total of 601 patients with the diagnosis of acute rhinosinusitis were included in this study. MRSA was isolated in 16 specimens. Its prevalence rate in acute rhinosinusitis was 2.7% (16 of 601). Multiple pathogens were more frequently found in children with MRSA infection. Five of seven adults had previous nasal procedures. Eight of nine children had a history of antibiotic use. Except for two patients without follow up, the remaining 14 patients resolved after receiving oral antibiotics according to culture results. CONCLUSIONS: The incidence of MRSA infection in acute rhinosinusitis was 2.7% in our study. The most important risk factor was nasal surgeries in adults and previous antibiotic use in children. The treatment outcome of community-acquired MRSA was excellent with oral antibiotics.

Acute Disease↗

IL-1 receptor-associated kinase 1 mediates protection against Staphylococcus aureus infection.

The interleukin-1 receptor-associated kinase-1 (IRAK-1) mediates signal transduction from Toll-like/IL-1/IL-18 receptors. Though a critical protective role against Staphylococcus aureus infection has been previously attributed to myeloid differentiation factor 88 (MyD88) and IRAK-4, both also involved in TLR/IL-1/IL-18 signaling, the role of IRAK-1 is unknown. IRAK-1-deficient (IRAK-1-/-) and wild-type mice were inoculated i.v. with 2 x 10(7) or 1 x 10(6) S. aureus per mouse to evaluate the role of IRAK-1 in S. aureus sepsis. Since IRAK-1 transduces IL-1R signals, IL-1R-/- mice were also included in experiments. IRAK-1-/- mice are susceptible to a high dose of S. aureus compared to wild-type controls. In contrast to the high mortality and extensive weight loss seen in IL-1R-deficient mice in response to 1 x 10(6) S. aureus, IRAK-1-/- mice are resistant to this low dose of S. aureus. Thus IRAK-1 plays an important role in the host response to staphylococcal sepsis.

Animals↗