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MRSA: status and prospects for therapy? An evaluation of key papers on the topic of MRSA and antibiotic resistance.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious nosocomial pathogen, and a related community-sourced MRSA is emerging. MRSA has evolved to become the major S. aureus phenotype in the hospital, emerging from just 30 to over 60% of the S. aureus population over the past 15 years. Together with its beta-lactam resistance, MRSA possesses multi-drug resistance genotype, including quinolones, macrolides and sulfonamides. MRSA has now emerged as the predominant nosocomial Gram-positive pathogen, and it has a high rate of mortality. Action must be taken to contain and eradicate MRSA through a combination of infection control and the development of novel anti-MRSA agents and vaccines.

Attitude to Health↗

[Methicillin-resistant Staphylococcus aureus (MRSA) infection--significance of MRSA in respiratory tract infection].

We have examined background factors in MRSA infection in cases in which S. aureus had been isolated from sputa. The incidence of isolation of S. aureus was high and still increasing in expectorated sputa, and causative organisms in the cases of pneumonia and autopsied lungs. A significant correlation was observed between high incidence of isolation of S. aureus and abuse of third-generation cephems. MRSA isolation rates of inpatients was higher than that of outpatients. Among the inpatients such cases with severe underlying diseases and prolonged admission showed the highest incidence of isolation of MRSA. There seemed to be a correlation between distribution of patients with S. aureus and that of rooms with S. aureus in the air. This suggests nosocomial infection. Although MRSA was frequently isolated from sputa, most cases showed no signs of infection, and this suggested that they had been transient colonization. Such antimicrobial agents as rifampicin, teicoplanin, vancomycin reveal excellent antibacterial activity against MRSA and minocycline, ofloxacin were moderately effective. The physician must be informed of the significance of MRSA, because their understanding of MRSA still remains insufficient.

Anti-Bacterial Agents↗

Epidemiological analysis of strains of methicillin-resistant Staphylococcus aureus (MRSA) infection in the nursery; prognosis of MRSA carrier infants.

Forty-five neonates who carried methicillin-resistant Staphylococcus aureus (MRSA) were studied. Retrospective molecular analysis using pulsed-field gel electrophoresis showed three separate MRSA epidemics in the nursery. Strains of MRSA isolated from the neonates were also isolated from the hospital environment and health care providers. Clinical manifestations included skin pustules (eight patients), conjunctivitis (four patients), or other minor infections (two patients). No neonate developed systemic infection. The prevalence of MRSA decreased with age. At one year, three (14.3%) of 21 infants that had carried MRSA at six days remained carriers and only two (1.1%) of 180 infants in a control 'S. aureus-negative at six days' group carried MRSA.

Age Distribution↗

Epidemiology of MRSA: the North/South study of MRSA in Ireland 1999.

The North/South Study of methicillin-resistant Staphylococcus aureus (MRSA) in Ireland, 1999, includes a joint review of the epidemiology of MRSA across both jurisdictions on the island of Ireland. Data were gathered on all MRSA cases identified in laboratories in Northern Ireland (the North) and in the Republic of Ireland (the South) over a two-week period. The prevalence rate per 100000 population was 11.4 in the North and 14.0 in the South, with a marked variation across geographical regions. MRSA cases were located throughout hospitals and the community, were slightly more common in males than females, and occurred in all age groups, especially in the elderly. The majority of cases were inpatients in acute hospitals and were distributed across all types of wards. Most cases were colonized with MRSA but 5% of cases in the North and 10% in the South had invasive infection. Invasive infection was associated with intravascular lines and invasive procedures/surgery. Continuous surveillance is recommended to monitor the epidemiology of MRSA and the effectiveness of control measures.

Adolescent↗

MRSA bacteraemia: North/South Study of MRSA in Ireland 1999.

Retrospective aggregate data on all Staphylococcus aureus isolates recovered from blood cultures during 1998 were collected in both jurisdictions on the island of Ireland, Northern Ireland (North) and the Republic of Ireland (South), as part of the North/South Study of MRSA in Ireland 1999. A postal questionnaire was used to gather the data, and all diagnostic microbiology laboratories in the North and 98% of laboratories in the South participated. S. aureus bacteraemia occurred at rates of 20.4 per 100,000 population in the North and 24.5 per 100,000 in the South (missing data from one laboratory). In the North, 22% of patients who had blood cultures positive for S. aureus had methicillin-resistant S. aureus (MRSA) and 25% of S. aureus isolates were MRSA (some patients had more than one isolate). In the South, 31% of patients who had blood cultures positive for S. aureus had MRSA and 36% of S. aureus isolates were MRSA. There was a marked variation in rates between different regions. The percentage of patients with blood cultures positive for S. aureus that had MRSA was considerably lower in the North (22%) than in the South (31%), and in both jurisdictions was lower than that found in England and Wales in 1999 (37%). It is recommended that data on S. aureus bacteraemia and methicillin-resistance rates (already available in many laboratories) are gathered at regional and national level for the surveillance of antimicrobial resistance.

Bacteremia↗

Evolution of sporadic isolates of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals and their similarities to isolates of community-acquired MRSA.

Forty-one methicillin-resistant Staphylococcus aureus (MRSA) hospital isolates that clearly differed from the six major pandemic clones of MRSA in pulsed-field gel electrophoresis type, mecA and Tn554 polymorphism, and epidemic behavior were selected from an international strain collection for more detailed characterization. SpaA typing, multilocus sequence typing, and SCCmec (staphylococcal cassette chromosome mec) typing demonstrated extensive diversity among these sporadic isolates both in genetic background and also in the structure of the associated SCCmec elements. Nevertheless, the isolates could be grouped into restricted clonal complexes by using the BURST (i.e., based upon related sequence types) program algorithm, which predicted that most sporadic MRSA isolates evolved from pandemic MRSA clones. Several of the sporadic MRSA resembled community-acquired MRSA isolates in properties that included a relatively limited multiresistance pattern, faster growth rates, diversity of genetic backgrounds, and a frequent association with SCCmec type IV.

Algorithms↗

[Isolation of methicillin-resistant Staphylococcus aureus (MRSA) from sputum and clinical features of bronchopulmonary infection due to MRSA during 4 years (1985-1988)].

Clinical and bacteriological studies were carried out to investigate the isolation of MRSA from sputa and 13 cases with bronchopulmonary infections due to MRSA, during 4 years from 1985 to 1988 at the Hokusyo Central Hospital. The isolation rate of MRSA in Staphylococcus aureus from sputum increased from 0% in 1985 to 51.4% in 1988, and especially from patients in wards for aged people. Most of the MRSA strains were isolated from patients with underlying diseases, or bed sores. The roentgenographic appearances in bronchopulmonary infection patients due to MRSA, showed infiltration and cavitation. Seven out of 13 cases of bronchopulmonary infection due to MRSA died, in spite of therapy with current antibiotics, suggesting poor prognosis of this infection.

Adult↗

In vitro antimicrobial activity of T-91825, a novel anti-MRSA cephalosporin, and in vivo anti-MRSA activity of its prodrug, TAK-599.

TAK-599 is a water-soluble prodrug of a cephalosporin compound, T-91825. In vitro and in vivo antibacterial activities of T-91825 and TAK-599, respectively, were examined. T-91825 was active against both gram-positive and gram-negative bacteria, unlike vancomycin and linezolid, which are inactive against gram-negative bacteria. The 90% minimum inhibitory concentration of T-91825 against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) was 2 micro g/ml. This activity was comparable to those of vancomycin, linezolid, teicoplanin, and arbekacin. T-91825 was similarly active against vancomycin-intermediate S. aureus. In a time-kill study, T-91825 showed more rapid and distinct decrease of viable cells of two MRSA strains than did vancomycin and linezolid in vitro. The effect of TAK-599 against systemic infection caused by clinical isolates of MRSA in mice was comparable or superior to that of vancomycin, linezolid, teicoplanin, and arbekacin. In addition, TAK-599 at a dose of 20 mg/kg significantly decreased bacterial counts in lungs of mice in an experimental pneumonia model caused by MRSA in which vancomycin and linezolid were totally ineffective at the same dose. These results suggest the usefulness of TAK-599 in the treatment of MRSA infections in humans.

Animals↗

Asymptomatic nasal carriage of mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) in a pet dog associated with MRSA infection in household contacts.

Recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection in a patient with diabetes and in his wife is described. Culture of nares samples from the family dog grew mupirocin-resistant (minimum inhibitory concentration >1024 microg/mL) MRSA that had a pulsed-field gel electrophoresis chromosomal pattern identical to the MRSA isolated from the patient's nares and his wife's wound. Further recurrence of MRSA infection and nasal colonization in the couple was prevented only after successful eradication of MRSA from the family dog's nares.

Animals↗

Multiplex PCR-ELISA for direct detection of MRSA in nasal swabs advantageous for rapid identification of non-MRSA carriers.

In the study presented here 251 nasal swabs obtained from medical staff were directly investigated for MRSA using a commercial multiplex PCR system in parallel with conventional culture methods to determine the usefulness of PCR for rapid screening. Both methods identified 3.2% (8/251) of specimens as MRSA-positive; one sample was culture-positive only, and three were PCR-positive only. PCR correctly identified 215 of 239 (90%) negative swab samples, but one sample with weak cultural growth was not detected and was therefore considered false negative. The comparative sensitivity of culture versus PCR was 75% (9/12) versus 91.6% (11/12). Although PCR had a low positive predictive value (31.4%) its negative predictive value was high (99.5%). The results of this study indicate the multiplex PCR is suitable for the rapid identification of MRSA-negative individuals directly from nasal swabs in populations with a low MRSA prevalence, but positive results need to be confirmed by culture.

Enzyme-Linked Immunosorbent Assay↗

Syntheses and anti-MRSA activities of the C3 analogs of mansonone F, a potent anti-bacterial sesquiterpenoid: insights into its structural requirements for anti-MRSA activity.

Syntheses and excellent anti-MRSA activities of the mansonone F analogs are reported. In addition, the minimal structural requirements for its anti-MRSA activities as well as its structure-activity relationship including the C3 substituents effects on anti-MRSA activity are also described. In particular, this study revealed that both ortho-quinone and tricyclic systems of mansonone F are essential for anti-MRSA activities.

Anti-Bacterial Agents↗

Community-adapted methicillin-resistant Staphylococcus aureus (MRSA): population dynamics of an expanding community reservoir of MRSA.

To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the community and their population dynamics, we studied the molecular epidemiology of a random sample (n=490) from a collection of 2154 inpatient and outpatient MRSA isolates during a 7-year period in San Francisco. We noted a progressive replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing isolates with type IV SCCmec-bearing isolates, which coincided with >4-fold increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing isolates involved in the increase in methicillin resistance belonged to 4 molecular genotypes. These 4 genotypes were associated predominantly with community-onset disease, rather than hospital- or long-term-care facility-onset disease (76.9% vs. 19.4% vs. 3.7%; P=.0005), suggesting that they are not feral descendants of hospital isolates. The longitudinal results linked the dramatic increase in MRSA infections to an expanding community reservoir of MRSA genotypes with intrinsic community survival advantage.

Anti-Bacterial Agents↗

Spread and maintenance of a dominant methicillin-resistant Staphylococcus aureus (MRSA) clone during an outbreak of MRSA disease in a Spanish hospital.

It was not until November 1989 that the 1,000-bed University-affiliated Hospital de Bellvitge "Princeps d'Espanya" in Barcelona first acquired methicillin-resistant Staphylococcus aureus (MRSA). Since that time, the outbreak of MRSA disease has continued. We have analyzed by genomic DNA fingerprinting 189 MRSA isolates collected between late 1989 and the end of 1993. The isolates include both invasive and colonizing strains as well as isolates from health-care workers and environmental sources. In addition, 52 clinical isolates of methicillin-susceptible S. aureus (MSSA) collected in the same hospital were also analyzed. Isolates were classified into clonal types on the basis of molecular typing techniques. A single MRSA clone (I::B::a) belonging to ClaI type I, pulsed-field gel electrophoretic pattern B, and Tn554 pattern a was responsible for the great majority of infections (73% of blood cultures and 79% of specimens from other clinical sources). This clone appeared at the very beginning of the outbreak, spread throughout the hospital wards, and was also carried by inpatients and health-care workers and on environmental surfaces. In contrast, no dominant lineage was apparent among MSSA isolates (33 distinct pulsed-field gel electrophoretic patterns among 52 isolates). Two MSSA isolates seem to have originated from the dominant clone by deletion of the mecA gene and some additional DNA. In several isolates, different mecA polymorphs were present in identical chromosomal backgrounds or cells with distinct chromosomal backgrounds carried the same mecA polymorph, suggesting horizontal transfer of the mecA gene.

Adult↗

Comparative cost of selective screening to prevent transmission of methicillin-resistant Staphylococcus aureus (MRSA), compared with the attributable costs of MRSA infection.

The annual cost of a screening program to detect methicillin-resistant Staphylococcus aureus (MRSA) in a teaching hospital in Spain was 10,261 Euro. The average cost per MRSA infection was 2,730 Euro; therefore, the cost of the program would be covered if it only prevented 4 infections per year (11% of the total number of MRSA infections at our hospital).

Costs and Cost Analysis↗

Genesis of methicillin-resistant Staphylococcus aureus (MRSA), how treatment of MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and the importance of antibiotic management and infection control.

We extensively studied the epidemiology and time course of endemic methicillin-resistant Staphylococcus aureus (MRSA) in the Millard Fillmore Hospital, a 600-bed teaching hospital in Buffalo. The changeover from methicillin-susceptible S. aureus to MRSA begins on the first hospital day, when patients are given cefazolin as presurgical prophylaxis. Under selective antibiotic pressure, colonizing flora change within 24 to 48 hours. For patients remaining hospitalized, subsequent courses of third-generation cephalosporins further select and amplify the colonizing MRSA population. Therefore, managing antibiotic selective pressure might be essential. Other strategies include attention to dosing, so that serum concentrations of drug exceed the minimum inhibitory concentration, and antibiotic cycling. Although there are some promising new antibiotics on the horizon, it is necessary to deal with many resistance patterns by using the combined strategies of infection control and antibiotic management.

Anti-Bacterial Agents↗

[Epidemiological investigation of beta-lactam antibiotic induced vancomycin-resistant MRSA from clinical isolated MRSA--comparison of detection rate of BIVR with or without CZX].

Recently, beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR) has been reported increasingly in Japan. Between 1998 and 2002, we tried to detect BIVR from 500 strains of MRSA in a cancer hospital. And the difference of the detection rate under condition of pre-culture with or without ceftizoxime was compared. The detection rate of BIVR under condition of pre-culture with 1.0 mg/L of ceftizoxime was 20.4% (102/500), and without ceftizoxime was 9% (45/500). That of preculture with 1.0 mg/L of ceftizoxime was higher than those without ceftizoxime with the significant difference. (p < 0.001; McNemar-t examination). In comparing each department, the detection rate of BIVR from Chemotherapy, Head & Neck, and Urology department was 33.3%, 27.0%, and 20.0%, respectively. These results mean that addition of beta-lactam as ceftizoxime in pre-culture induces the ability of resistance to vancomycin for MRSA having a capacity as BIVR.

Anti-Bacterial Agents↗

MRSA - 'bug-bear' of a surgical practice: reducing the incidence of MRSA surgical site infections.

Adverse publicity (the 'superbug') has demonstrated that the problem of MRSA (methicillin-resistant Staphylococcus aureus) is prevalent in many of the country's most prestigious hospitals. The results of the mandatory UK Department of Health (DH) surveillance for early surgical site infections in orthopaedic surgery (SSIS) have been published recently for the period April 2004 to March 2005 when 41,242 operations were studied ( 28 October 2005). Infection rates were generally and gratifyingly low but 48% of surgical site infections were caused by Staph. aureus and of those 68% were MRSA. The following article will discuss the aetiology and prevention of MRSA surgical site infection.

Antibiotic Prophylaxis↗

Postoperative complications due to methicillin-resistant Staphylococcus aureus (MRSA) in an elderly patient: management and control of MRSA.

An elderly lady was admitted to hospital for elective resection of an adenocarcinoma of the colon. Following an anastomotic leak she developed intra-abdominal sepsis and underwent abdominal drainage of pus. During recovery from her second operation, she developed pneumonia and a bacteraemia due to methicillin-resistant Staphylococcus aureus (MRSA). She was treated with vancomycin and co-trimoxazole and survived without further sequelae. Details of the development and treatment of this case are discussed. Procedures for the control and eradication of MRSA infections in hospitals are reviewed.

Adenocarcinoma↗