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PubMed1994

Comparison of the virulence of methicillin-resistant and methicillin-sensitive Staphylococcus aureus.

The virulence of methicillin-resistant Staphylococcus aureus (MRSA) was compared with that of methicillin-sensitive S. aureus (MSSA), using 13 MRSA and 7 MSSA strains isolated from clinical specimens. The infectivity and lethality of the two groups were examined as to the inoculum required to infect 50% of guinea pigs (ID50) and to kill 50% of mice (LD50), respectively. The mean ID50 [log10 colony forming units (CFU)] for MRSA strains was 7.1 +/- 0.60 standard deviation, which was 1.5 higher than that for MSSA strains (P < 0.001). The mean LD50 (log10 CFU) for MRSA strains was 9.0 +/- 0.42, being 1.1 higher than that for MSSA strains (P = 0.001). Pretreatment of mice with cyclophosphamide decreased the mean LD50 for MRSA strains more than that for MSSA strains, resulting in the difference in the mean LD50 being insignificant (P = 0.502). These results indicate that MRSA is less virulent than MSSA in normal hosts, but that they are equally virulent in immunocompromised hosts. The growth of MRSA strains was much slower than that of MSSA strains in the lag phase, although their growth rates were almost the same in the exponential growth phase, suggesting that the difference in virulence between them may be at least partly due to such a difference in growth.

Animals↗

PubMed1993

Abnormal peptidoglycan produced in a methicillin-resistant strain of Staphylococcus aureus grown in the presence of methicillin: functional role for penicillin-binding protein 2A in cell wall synthesis.

Upon the addition of methicillin even at relatively low concentrations (5 mug/ml or 0.3% of the MIC) to the medium, methicillin-resistant staphylococci shift to the production of a new peptidoglycan with an abnormal muropeptide composition which may be the synthetic product of penicillin-binding protein 2A.

Amino Acid Sequence↗

PubMed1997

Cell wall monoglycine cross-bridges and methicillin hypersusceptibility in a femAB null mutant of methicillin-resistant Staphylococcus aureus.

The femAB operon is involved in the formation of the characteristic pentaglycine side chain of the staphylococcal peptidoglycan. Allele replacement of the femAB operon with the tetracycline resistance determinant tetK in a methicillin-resistant Staphylococcus aureus strain resulted in impaired growth, methicillin hypersusceptibility, and lysostaphin resistance. The usual pentaglycine cross-bridges were replaced by monoglycine bridges exclusively, and cross-linking of the peptidoglycan strands was drastically reduced. Complementation of the femAB null mutant by either femA or femAB resulted in the extension of the cross-bridges to a triglycine or a pentaglycine, respectively. This finding suggests that FemA is responsible for the formation of glycines 2 and 3, and FemB is responsible for formation of glycines 4 and 5, of the pentaglycine side chain of the peptidoglycan precursor. Moreover, it can be deduced that addition of the first glycine must occur by a femAB-independent mechanism.

Amino Acids↗

PubMed2006

Heterogeneity of methicillin-susceptible Staphylococcus aureus strains at a German University Hospital implicates the circulating-strain pool as a potential source of emerging methicillin-resistant S. aureus clones.

Recently, we demonstrated rapid dissemination of different methicillin-resistant Staphylococcus aureus (MRSA) clones at the Institute for Microbiology at the University of Magdeburg (B. Ghebremedhin, W. König, and B. König, Eur. J. Clin. Microbiol. Infect. Dis. 24:388-398, 2005). The majority of them harbored the readily transmissible mec cassette type IV. Thus, theoretically, methicillin-susceptible Staphylococcus aureus (MSSA) might capture the mecA gene from circulating MRSA, or MRSA strains might catch mobile toxin genes from MSSA. Therefore, we characterized MSSA strains circulating at the University Hospital in Magdeburg. Among a total of 84 MSSA strains under study, about 40% possessed the tst (toxic shock syndrome toxin) gene and up to four additional enterotoxin genes. tst-positive MSSA strains belonged to all known agr groups (I to IV) and to 14 different spa types (t008, t012, t015, t019, t024, t056, t065, t127, t133, t162, t271, t287, t399, and t400), and they were classified by multilocus sequence typing (MLST) as ST1, ST8, ST30, ST39, ST45, ST101, ST121, ST395, and ST426. In contrast, simultaneously circulating MRSA strains (n = 24) harbored in general two or three genes of the enterotoxin gene cluster, and the tst-positive MRSA isolates belonged to the well-known epidemic types ST22, ST45, and ST228 and were classified as spa types t001, t028, and t032. From our results, one may conclude that the pool of circulating MSSA strains is an important parameter with regard to the epidemiology of hospital- and community-acquired MRSA clones and their potential virulence.

Anti-Bacterial Agents↗

PubMed2000

Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus.

A multilocus sequence typing (MLST) scheme has been developed for Staphylococcus aureus. The sequences of internal fragments of seven housekeeping genes were obtained for 155 S. aureus isolates from patients with community-acquired and hospital-acquired invasive disease in the Oxford, United Kingdom, area. Fifty-three different allelic profiles were identified, and 17 of these were represented by at least two isolates. The MLST scheme was highly discriminatory and was validated by showing that pairs of isolates with the same allelic profile produced very similar SmaI restriction fragment patterns by pulsed-field gel electrophoresis. All 22 isolates with the most prevalent allelic profile were methicillin-resistant S. aureus (MRSA) isolates and had allelic profiles identical to that of a reference strain of the epidemic MRSA clone 16 (EMRSA-16). Four MRSA isolates that were identical in allelic profile to the other major epidemic MRSA clone prevalent in British hospitals (clone EMRSA-15) were also identified. The majority of isolates (81%) were methicillin-susceptible S. aureus (MSSA) isolates, and seven MSSA clones included five or more isolates. Three of the MSSA clones included at least five isolates from patients with community-acquired invasive disease and may represent virulent clones with an increased ability to cause disease in otherwise healthy individuals. The most prevalent MSSA clone (17 isolates) was very closely related to EMRSA-16, and the success of the latter clone at causing disease in hospitals may be due to its emergence from a virulent MSSA clone that was already a major cause of invasive disease in both the community and hospital settings. MLST provides an unambiguous method for assigning MRSA and MSSA isolates to known clones or assigning them as novel clones via the Internet.

Bacterial Typing Techniques↗

PubMed2003

Effect of duplicate isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus on antibiogram data.

Duplicate Staphylococcus aureus isolates were analyzed to determine the impact of multiple isolates from the same patient on annual antibiogram data. During a 6-year period (1996 to 2001), 3,227 patients with 4,844 S. aureus isolates were evaluated. A total of 39% of patients with methicillin-resistant S. aureus (MRSA) (n = 860) and 23% of patients with methicillin-susceptible S. aureus (MSSA) (n = 2,367) infections had duplicate isolates. Cumulative data show that 91% of the patients during this 6-year period with duplicate isolates (2 to 13 duplicates/year) did not switch between MSSA and MRSA but retained the original S. aureus strain whether it was MSSA or MRSA. Rates of MRSA were calculated for each year by using all isolates and then eliminating duplicates. The impact of duplicate MRSA and MSSA isolates was evaluated by using the ratio of isolates per patient such that ratios of >1.0 indicate >1 isolate per patient. The 6-year ratio for MRSA was 1.90 isolates/patient, and the ratio for MSSA was 1.35. A significant difference (P < 0.05) was noted in the MRSA rates in 4 of 6 years when duplicate isolates were removed. Common phenotypic antibiogram patterns were compared for all MRSA isolates during the 6-year period, and 64% were of a single antibiogram phenotype. Eighty-eight percent of patients with duplicate MRSA isolates had phenotypically identical multiple isolates. The rate of MRSA differs when duplicate isolates are removed from the antibiogram data.

Anti-Bacterial Agents↗

PubMed2003

Genetic relationship between methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains from France and from international sources: delineation of genomic groups.

Cluster analysis of the SmaI patterns, generated by pulsed-field gel electrophoresis, of 44 methicillin-resistant (MRSA) and 118 methicillin-sensitive (MSSA) Staphylococcus aureus strains isolated in various French hospitals and 61 MRSA and 48 MSSA strains from 20 other countries revealed 20 genomic groups distributed into four distantly related phylogenic branches. Eighty-three of the 105 MRSA strains (79%) were clustered in the six genomic groups of phylogenic branch I; and 154 of the 166 MSSA strains (92.8%) were clustered in the 14 genomic groups of phylogenic branches II, III, and IV. Agreement between genomic group and two other markers, esterase type and phage group, was obtained, emphasizing the clonal structure of the population. The genomic groups were delineated by esterase type. The distribution of the strains within the genomic groups was independent of their geographical origin; French strains were clustered with strains from other countries. The three types of the staphylococcal cassette chromosome mec (SCCmec) complex were distributed according to genomic groups. Most of the time, type I and type II SCCmec complexes were found in the MRSA strains belonging to the same genomic groups. In contrast, the type III SCCmec complex was specific to the MRSA strains belonging to the three genomic groups characterized by a common esterase type.

Bacteriophage Typing↗

PubMed1994

Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes.

All episodes of ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus were prospectively analyzed for a 30-mo period. Methicillin-sensitive S. aureus (MSSA) was isolated in 38 episodes and methicillin-resistant S. aureus (MRSA) in 11 others. The two groups were similar regarding sex, severity of underlying diseases, prior surgery, and presence of renal failure, diabetes, cardiopathy, and coma. MRSA-infected persons were more likely to have received steroids before developing infection (relative risk [RR] = 3.45, 95% confidence interval [CI] = 1.38-8.59), to have been ventilated > 6 d (RR = 2.03, 95% CI = 1.36-3.03), to have been older than 25 yr (RR = 1.50, 95% CI = 1.09-2.06), and to have had preceding chronic obstructive pulmonary disease (RR = 2.76, 95% CI = 0.89-8.56) than MSSA-infected patients. MSSA-infected persons were more likely than MRSA-infected patients to have cranioencephalic trauma (RR = 1.94, 95% CI = 1.22-3.09). All patients with MRSA VAP had previously received antibiotics, compared with only 21.1% of those with MSSA infection (p < 0.000001). The incidence of empyema was similar in both groups; nevertheless, the presence of bacteremia and septic shock was more frequent in the MRSA group. Finally, mortality directly related to pneumonia was significantly higher among patients with MRSA episodes (RR = 20.72, 95% CI = 2.78-154.35). This analysis was repeated for monomicrobial episodes, and the difference remained statistically significant. We conclude that MRSA and MSSA strains infect patients with different demographic profiles; previous antibiotic therapy is the most important risk factor for developing MRSA infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2003

Colonization of HIV-infected outpatients in Taiwan with methicillin-resistant and methicillin-susceptible Staphylococcus aureus.

To better understand the epidemiology of bacterial pathogens with particular public health importance in Taiwan, we determined the prevalence of nasal colonization with methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in a cohort of HIV-infected patients attending two hospital outpatient departments. All HIV-infected patients followed regularly between May and September 1999 were enrolled and cultures of the anterior nares were performed using a dry sponge swab. All confirmed S. aureus isolates underwent antimicrobial susceptibility testing using disk diffusion according to recommendations of the National Committee for Clinical Laboratory Standards. Of a total of 162 outpatients studied, 48 (30%) were found colonized with S. aureus including 39 (24%) colonized with MSSA and 9 (6%) colonized with MRSA. The only factor associated with MSSA colonization was receipt of trimethoprim-sulphamethoxazole which appeared protective (relative risk 0.4, 95% confidence interval [CI(95)] 0.2-0.78, P = 0.006). In contrast, ciprofloxacin use was an independent risk factor for MRSA colonization (conditional odds ratio [OR] 11.9, CI(95) 1.8-77.8, P = 0.010) along with a one-quartile reduction in CD(4) count (OR 3.9, CI(95) 1.1-14.3, P = 0.04). Although MRSA colonization was not associated with hospitalization within the previous three months, the multi-drug resistance pattern of MRSA isolates suggests strains were at some point acquired in the healthcare setting. Our study shows that the rate of S. aureus colonization in Taiwanese HIV-infected outpatients is 30%. Low CD4+ counts are most likely associated with other unmeasured risk factors for MRSA. Antimicrobial use may function alternatively as a protective or risk factor for colonization with S. aureus, depending upon the drugs involved and resistance encountered. Fluoroquinolone use may have an important role in the spread of MRSA from inpatient to outpatient settings.

Adult↗

PubMed2001

Comparison of the effects in vitro of tea tree oil and plaunotol on methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus.

The effects in vitro of tea tree oil (TTO) and plaunotol were examined by monitoring the growth of a standard strain of Staphylococcus aureus FDA 209P and of fourteen methicillin-susceptible strains of S. aureus (MSSA), together with twenty methicillin-resistant strains (MRSA). The minimum inhibitory concentrations (MIC) and the doses for 50% inhibition of growth (ID50) were determined by the micro-broth dilution (MD) method, and the broth dilution with shaking (BDS) method, respectively. The MIC of plaunotol for 50 and 90% of the MSSA and MRSA were assessed by the MD method, as 16 microg/ml and > or = 1,024 microg/ml, respectively. No antibacterial effects of TTO on MSSA and MRSA were detected by the MD method. The growth-inhibitory effects of TTO on S. aureus by the BDS method were examined, and it appeared that TTO was effective over a lower range of concentrations than previously reported. It seems that TTO is very effective in vitro against MSSA and MRSA at high concentrations but less effective below 40 microg/ml of TTO.

Anti-Bacterial Agents↗

PubMed1993

Comparison of bactericidal activities of various disinfectants against methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

Various disinfectants were compared in terms of the duration of bactericidal activity against methicillin-sensitive Staphylococcus aureus (MSSA), and methicillin-resistant Staphylococcus aureus (MRSA), among S. aureus isolated in our hospital. Strains of S. aureus which showed minimum inhibitory concentrations of cloxacillin of less than 1.56 micrograms/ml and of 3.13 micrograms/ml or higher were designated MSSA and MRSA respectively. There was no difference in sensitivity to disinfectants between MSSA and MRSA. There was a great variation in the duration of bactericidal activity of chlorhexidine gluconate against these species with the majority requiring contact times of between 2 minutes and over 20 minutes. All strains except for one strain of MRSA were killed within 20 seconds after disinfection with benzalkonium chloride. All strains were killed within 20 seconds after disinfection with alkyldiaminoethylglycine hydrochloride or povidone-iodine.

Benzalkonium Compounds↗

PubMed1987

In vitro activity of ciprofloxacin against methicillin-susceptible and methicillin-resistant staphylococci.

Ciprofloxacin was found to be active against selected strains of methicillin-resistant as well as methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis, having minimal inhibitory concentrations less than 0.8 micrograms/ml with inocula of approximately 10(4) CFU/ml. When killing kinetic studies were done with inocula of approximately 10(6) CFU/ml and various ciprofloxacin concentrations, the killing effect was low (less than 3 log10 in 6 h) and regrowth of the culture was seen after 24 h in at least one Staphylococcus aureus strain. After 48 h incubation, mutants with MICs eightfold that of the parental strain had grown to a number of approximately 10(10) CFU/ml.

Ciprofloxacin↗

PubMed2001

Staphylococcus aureus meningitis in adults: a clinical comparison of infections caused by methicillin-resistant and methicillin-sensitive strains.

BACKGROUND: This study was undertaken to compare the clinical characteristics of adult methicillin-sensitive Staphylococcus aureus (MSSA) meningitis and adult methicillin-resistant S. aureus (MRSA) meningitis. PATIENTS AND METHODS: The clinical characteristics and therapeutic outcomes of 19 adult patients with S. aureus meningitis, including eight with MSSA infections and 11 with MRSA infections, were analyzed. A comparison was made between the clinical data of the patients with MSSA infections and those with MRSA infections. RESULTS: Before the end of 1995, MSSA infection was involved in all the adult patients with S. aureus meningitis but thereafter, MRSA infection was involved in 79% of the cases. The clinical characteristics found in patients with MSSA infection included underlying medical disorders (75%), community-acquired infection (75%) and mortality rate (13%). The clinical characteristics found in patients with MRSA infection included post-neurosurgical states (91%), nosocomial infections (100%), men outnumbering women (8:3), hydrocephalus (36%) and mortality rate (56%). Comparative study between the patient groups (hematogenous and post-neurosurgical) showed that only the mode of acquisition of infection had statistical significance. CONCLUSIONS: This study showed an increase in MRSA infections in adult S. aureus meningitis in recent years. The clinical characteristics of patients with MSSA and MRSA meningitis were different. Community-acquired infection was common in hematogenous S. aureus meningitis, while nosocomial infection was common in post-neurosurgical S. aureus meningitis. Vancomycin should be considered as one of the drugs of choice for initial therapy of adult bacterial meningitis, especially in post-neurosurgical patients.

Adolescent↗

PubMed1990

Hong Kong strains of methicillin-resistant and methicillin-sensitive Staphylococcus aureus have similar virulence.

While most authorities agree that methicillin-resistant Staphylococcus aureus (MRSA) are as pathogenic as methicillin-sensitive strains (MSSA), some believe that MRSA are relatively avirulent opportunists, and that their importance has been exaggerated. We present evidence that Hong Kong strains of MRSA and MSSA are equally pathogenic: they have similar virulence in animal models; they are isolated in similar proportions from both deep and superficial clinical sites including blood; in patients with hospital-acquired bacteraemias mortality rates are similar when adjusted for clinical factors; and in both animals and patients with systemic MRSA infection, mortality rates are significantly reduced by vancomycin therapy. Efforts to control the spread of MRSA are justified, and in invasive sepsis early treatment with vancomycin may be life-saving.

Animals↗

PubMed1992

Fosfomycin enhances the expression of penicillin-binding protein 2 in methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains.

The effects of fosfomycin on penicillin-binding proteins (PBPs) were studied on the methicillin-resistant Staphylococcus aureus strain CIP (Collection de l'Institut Pasteur, Paris, France) 65-25 and on a methicillin-susceptible S. aureus strain CIP 65-6. The combinations of fosfomycin and oxacillin were synergistic, additive or antagonistic, depending on antibiotic concentrations. Fosfomycin induced modifications of the PBP profile of the two strains studied. In particular, it increased the expression of PBP2. This suggested that this protein is inducible; the only PBP not affected by fosfomycin was PBP3.

Bacterial Proteins↗

PubMed2004

Staphylococcus aureus bacteremia and endocarditis: the Grady Memorial Hospital experience with methicillin-sensitive S aureus and methicillin-resistant S aureus bacteremia.

BACKGROUND: Staphylococcus aureus has become the leading cause of endocarditis in most published series, and nosocomial acquisition is becoming more frequent. Previous studies involved community acquired methicillin-sensitive S aureus (MSSA), but recently, methicillin-resistant S aureus(MRSA) infection has increased. This may reflect the growing presence of this microorganism in clinical practice. Few data exist comparing the relative rates of endocarditis with MSSA and MRSA bacteremia. The purpose of this study was to compare these rates in a bacteremic population referred for diagnostic echocardiography. METHODS: Since July 1999, the demographic and clinical information of 104 consecutive patients with at least 2 blood cultures with positive results for S aureus who were referred for echocardiography to be evaluated for endocarditis at Grady Memorial Hospital (Atlanta, Ga) have been entered into a database. This database has further been restricted to patients who have undergone either a transesophageal echocardiogram or a transthoracic echocardiogram. RESULTS: Of the 104 patients with S aureus bacteremia, 53 had an infection of MSSA and 51 had an infection of MRSA. There were 33 patients (31.7%) with echocardiographically confirmed endocarditis, 23 patients (43.4%) in the MSSA group versus 10 patients (19.6%) in the MRSA group (P <.009). Community-acquired MSSA bacteremia was the cause of most of the community-acquired S aureus endocarditis (20 patients [87%] vs 3 patients [30%], P =.004), and the nosocomial-acquired MRSA bacteremia was the cause of most of the nosocomial-acquired S aureus endocarditis (3 patients [13%] vs 7 patients [70%], P =.0001). CONCLUSION: Our study confirms that S aureus bacteremia is associated with high rates of endocarditis. MSSA bacteremia is associated with higher rates of endocarditis than MRSA. Community MSSA is the cause of most of the community endocarditis, whereas nosocomial MRSA is the cause of most of the MRSA endocarditis. Patients with S aureus bacteremia should be aggressively evaluated for endocarditis.

Adult↗

PubMed2004

RNAIII-inhibiting peptide and/or nisin inhibit experimental vascular graft infection with methicillin-susceptible and methicillin-resistant Staphylococcus epidermidis.

OBJECTIVE: To investigate the efficacy of RNAIII-inhibiting peptide (RIP) and nisin as prophylactic agents in a rat model of vascular graft infection. DESIGN: Prospective, randomized, controlled animal study. MATERIALS: Two hundred and twenty adult male Wistar rats. Staphylococcus epidermidis ATCC 12228 and one clinical isolate of methicillin-resistant S. epidermidis. Drugs: RIP, nisin and rifampin. METHODS: Graft infections were established in the dorsal subcutaneous tissue by implantation of 1 cm(2) sterile Dacron grafts, followed by topical bacterial inoculation: grafts were retrieved at 7 days. The study included a control group (without inoculation) and two series composed of five groups for each staphylococcal strain: one contaminated group that did not receive any antibiotic prophylaxis, three contaminated groups that received grafts soaked with 10 mg/l RIP, 10 mg/l nisin, 10 mg/l rifampin, or RIP+nisin. The main outcome measure was the extent of bacterial at graft harvest. RESULTS: The bacterial counts for methicillin-resistant S. epidermidis on explanted grafts were 6.1+/-2.8x10(2), 7.8+/-3.0x10(3) and 5.5+/-2.9x10(4) for RIP, nisin and rifampin, respectively. RIP and nisin used in combination reduced the bacterial count to <10. The results for S. epidermidis were similar. CONCLUSIONS: RIP and nisin could be used in combination to coat medical devices to prevent drug resistant S. epidermidis infections.

Animals↗

PubMed2003

Interaction between methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA).

In this paper we describe the in vitro interaction between three strains of methicillin-sensitive Staphylococcus aureus (MSSA) [NCTC 11561 and two strains derived from patients (PMSSA)] and endemic methicillin-resistant Staphylococcus aureus (EMRSA) 1, 3, 15 and 16. Mixed bacterial cultures of MSSA and EMRSA were incubated and subcultured after one, two and seven days. A proportion of MRSA in 50 randomly selected colonies was assessed. All strains of EMRSA (EMRSA 1, 3, 15 and 16) outgrew and virtually eradicated MSSA (NCTC 11561) after 24 h. The interaction between strains of PMSSA and the various strains of EMRSA was variable. PMSSA strain 1 was almost completely outgrown by EMRSA 1 and EMRSA 3 after seven days. Similarly there was a substantial increase of EMRSA 1 and 3 when tested against PMSSA strain 2. EMRSA 15 increased modestly against both strains, but EMRSA 16 failed to increase in proportion against either of the strains. We conclude that there is a complex interaction between various strains of EMRSA and MSSA. This interaction may have an important bearing on colonization of patients with MRSA.

Antibiosis↗