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PubMed2004

[Epidemiological study of Arbekacin-resistant, methicillin resistant Staphylococcus aureus in Saitama Medical School Hospital].

Arbekacin-resistant, methicillin-resistant Staphylococcus aureus was frequently isolated in Saitama Medical School Hospital during 1996 and 1998. The minimum inhibitory concentration for ABK was 8 micrograms/ml in 14 strains, 16 micrograms/ml in 6 strains, and 32 micrograms/ml in 2 strains. The maximum isolation rate of these resistant strains in one month was 8%. Use of ABK in the hospital did not increase during the same period. The infection control team (ICT) of the hospital recognized the increase of resistant strains and started intervention for the hospital staff. The ICT instructed the staff of each ward to follow standard precautions for the prevention of nosocomial infections and the risk of ABK-resistant MRSA was explained repeatedly. Thereafter, the isolation rate decreased to 3%. An epidemiological study was done using 22 strains of ABK-resistant MRSA that were isolated in this period. The strains originated from different patients and from 10 different wards, which were designated as wards A to J. Eight strains were isolated from surgical ward A, followed by the other wards (ward B: 3, C: 2, D: 2, E: 2, F: 1, G: 1, H: 1, I: 1, J: 1). The specimens from which ABK-resistant MRSA were isolated were as follows,: sputum: 4, wound: 4, decubitus ulcer: 4, urine: 2, pus: 2, blood :1, central venous catheter: 1, drainage tube: 1, tracheal aspirate: 1, skin: 1, stool: 1. Several investigations were done using these strains. Sensitivity tests for ABK, VCM, MINO, LVFX, FOM, IPM were performed by the standard method of the Japan Society for Chemotherapy. Coagulase types were determined. Production of toxic shock syndrome toxin-1 (TSST-1), enterotoxin, and beta-lactamase was assayed. Pulse-field gel electrophoresis (PFGE) using Sma I was also done and differences were compared. Seven of the 8 strains from ward A showed the same drug sensitivity profile and biological phenotype. Two of the 3 strains from ward B and 2 strains from ward C were also identical by these methods. Six of the 8 strains from ward A were also identical by PFGE. These 6 isolates showed the same drug sensitivity pattern, same coagulase type, and same production of TSST-1 and enterotoxin. Two other strains from ward B, one strain from ward F, and one from ward I also showed the same PFGE pattern, drug sensitivity profile, and toxin profile as the 6 strains from ward A. Our data show that the same strains were transmitted around the hospital during the study period, although serious nosocomial infections due to ABK-resistant MRSA were avoided. Thus, intervention by the ICT in each ward was effective. ABK-resistant MRSA should be recognized as an important hospital pathogen and should be surveyed consistently.

Aminoglycosides↗

PubMed1998

Role of fem factors in methicillin resistance.

Methicillin resistance in Staphylococcus aureus is primarily due to the acquisition of an additional penicillin-binding protein, PBP2' (also known as PBP2a), that confers resistance to virtually all beta-lactam antibiotics. This foreign PBP2' has strict requirements on peptidoglycan precursor formation and composition in order to function optimally. The level of methicillin resistance is governed by genomic factors which are involved in cell wall metabolism and/or are constituents of the cytoplasmic membrane. The formation of the pentaglycine interpeptide bridge of peptidoglycan plays a key function and depends on at least three factors, FemX, FemA and FemB.

Journal Article↗

PubMedDate not supplied

Molecular fingerprinting of mupirocin-resistant methicillin-resistant Staphylococcus aureus from a burn unit.

OBJECTIVES: To characterize mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients in a burn unit by pulsed-field gel electrophoresis and plasmid contents. METHODS: A total of 53 methicillin-resistant S. aureus, consisting of 48 mupirocin-resistant and 5 mupirocin-susceptible MRSA were compared by plasmid content and pulsed-field gel electrophoresis of Sma I digested genomic DNA. RESULTS: Of the 48 mupirocin-resistant isolates, 39 expressed high-level, and 9 expressed low-level mupirocin resistance. Plasmids were detected in all of the 53 isolates; however, only the high-level mupirocin-resistant isolates contained a 38 kb-conjugative plasmid that encoded high-level mupirocin resistance. Pulsed-field gel electrophoresis divided the isolates into four patterns designated types I to IV. Forty-three isolates consisting of 34 high-level, 5 low-level mupirocin-resistant and 4 mupirocin-susceptible isolates defined the type-I pattern. Eight isolates, five high-level and three low-level mupirocin-resistant isolates had the type-II pulsed-field pattern. The type-III and type-IV pulsed-field patterns consisted of a single isolate each. The type-I and type-II pulsed-field patterns were related and only differed by four Sma I bands. CONCLUSIONS: Results of typing the mupirocin-resistant MRSA from the burn unit with pulsed-field gel electrophoresis indicated that closely related MRSA clones previously circulating in the unit had acquired a high-level mupirocin-resistant plasmid, and spread aided by mupirocin use.

Anti-Bacterial Agents↗

PubMed1998

Acquisition of methicillin resistance and progression of multiantibiotic resistance in methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) produces specific penicillin-binding protein, PBP2', which shows remarkably low affinities to most beta-lactam antibiotics except those such as penicillin G and ampicillin. The region surrounding mecA has been called additional DNA or mec and is thought to be of extraspecies origin. From the study of mec, we found that mec is a novel mobile genetic element and designated as staphylococcal cassette chromosome mec (SCCmec). There are three types of SCCmec. In the past decades, MRSA has become resistant to many antibiotics, such as carbapenems, new quinolones, and minocycline etc. It seems to be a characteristic of MRSA to acquire multi-resistance by accumulating multiple resistance genes around the mecA gene inside SCCmec.

Drug Resistance, Microbial↗

PubMed1995

Treatment of experimental endocarditis due to erythromycin-susceptible or -resistant methicillin-resistant Staphylococcus aureus with RP 59500.

RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against erythromycin-susceptible and -resistant gram-positive pathogens. The present experiments compared the therapeutic efficacy of RP 59500 with that of vancomycin against experimental endocarditis due to either of two erythromycin-susceptible or two constitutively erythromycin-resistant isolates of methicillin-resistant Staphylococcus aureus. RP 59500 had low MICs for the four test organisms as well as for 24 additional isolates (the MIC at which 90% of the isolates were inhibited was < 1 mg/liter) which were mostly inducibly (47%) or constitutively (39%) erythromycin resistant. Aortic endocarditis in rats was produced with catheter-induced vegetations. Three-day therapy was initiated 12 h after infection, and the drugs were delivered via a computerized pump, which permitted the mimicking of the drug kinetics produced in human serum by twice-daily intravenous injections of 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Both antibiotics reduced vegetation bacterial titers to below detection levels in ca. 70% of animals infected with the erythromycin-susceptible isolates (P < 0.05 compared with titers in controls). Vancomycin was also effective against the constitutively resistant strains, but RP 59500 failed against these isolates. Further experiments proved that RP 59500 failures were related to the very short life span of dalfopristin in serum (< or = 2 h, compared with > or = 6 h for quinupristin), since successful treatment was restored by artificially prolonging the dalfopristin levels for 6 h. Thus, RP 59500 is a promising alternative to vancomycin against methicillin-resistant S. aureus infections, provided that pharmacokinetic parameters are adjusted to afford prolonged levels of both of its constituents in serum. This observation is also relevant to humans, in whom the life span of dalfopristin in serum is also shorter than that of quinupristin.

Animals↗

PubMed1990

Ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus in an acute-care hospital.

Use of ciprofloxacin as an alternative to vancomycin for treatment of methicillin-resistant Staphylococcus aureus infection has been paralleled by the emergence of resistant strains. This phenomenon has also been noticed in our hospital. To confirm our observation, methicillin and ciprofloxacin susceptibilities were tested by disk diffusion and broth microdilution techniques. We studied 83 methicillin-resistant Staphylococcus aureus isolates obtained from various sources over a 4-month period. Ciprofloxacin resistance (MIC, greater than 2 micrograms/ml) was detected in 69 isolates (83%). Prior use of ciprofloxacin was reported for 24 of 69 patients with ciprofloxacin-resistant strains and 0 of 14 patients with ciprofloxacin-susceptible strains. The day of detection during the hospital stay and the location of the source patient were not significantly different between resistant and susceptible strains. Bacteriophage typing showed a higher occurrence of nontypeable strains among ciprofloxacin-resistant strains (54%). Review of our microbiology register showed a progressive increase in the rate of resistance to ciprofloxacin during the first year of use, with initial rates being about 10% and recent rates being higher than 80%. On the other hand, methicillin-susceptible S. aureus remained uniformly susceptible to ciprofloxacin (98.4%). We conclude that prior use of ciprofloxacin is an important factor for the selection of ciprofloxacin-resistant strains and that ciprofloxacin has limited usefulness against methicillin-resistant S. aureus.

Acquired Immunodeficiency Syndrome↗

PubMed1977

Mutations in prophage phi11 that impair the transducibility of their Staphylococcus aureus lysogens for methicillin resistance.

Methicillin resistance (mec) is not transduced into Staphylococcus aureus 8325-4, but is transduced into this host after it has been lysogenized with phage phi11 and has acquired the penicillinase plasmid pI524 by a separate transduction (Cohen and Sweeney, 1970, 1973). Strain 8325-4 is competent for transformation of typical plasmid or chromosomal markers and for mec only if it is lysogenic for phi11 or a related prophage (Sjöström et al., 1974, 1975). A mutant strain of phi11 that was temperature sensitive (Ts) for vegetative multiplication did not mediate competence for transformation of its 8325-4 lysogen if the lysogen had been grown at a nonpermissive temperature (Sjöström and Philipson, 1974). We isolated four Ts mutants of phi11 that did not mediate transducibility of their 8325-4(pI524) lysogens for mec after growth at nonpermissive temperatures (40 to 42 degrees C). Transduction of typical plasmid or chromosomal markers was not affected. These phi11-Ts mutants mediated normal competence of their lysogens for transformation of a tetracycline resistance plasmid. Similarly, phi11-Ts mutants that rendered their lysogens temperature sensitive for transformation did not depress the frequency of transduction of mec. These two types of phi11-Ts mutants fell into two different genetic complementation groups that differed in the physiology of deoxyribonucleic acid synthesis and in the time of expression of the mutations during a single-burst growth cycle at a nonpermissive temperature. A virulent mutant of phi11, which plaqued with 100% efficiency on 8325(phi11), also failed to condition strain 8325-4 for transducibility of mec but retained the ability to confer competence for transformation of a tetracycline resistance plasmid. Different genetic loci and physiological functions are involved in phi11 mutations that affect transducibility of mec and those that affect competence for transformation of markers generally in S. aureus 8325-4.

DNA, Viral↗

PubMed2005

Daptomycin-resistant, methicillin-resistant Staphylococcus aureus bacteremia.

We describe a patient who developed daptomycin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) during an episode of presumed septic thrombophlebitis of the portal vein. Although daptomycin is an alternative agent for treatment of drug-resistant gram-positive bacterial infections, development of resistance during prolonged use may occur with MRSA bacteremia from a persistent focus.

Anti-Bacterial Agents↗

PubMed2000

Genetic relatedness of multidrug-resistant, methicillin (oxacillin)-resistant Staphylococcus aureus bloodstream isolates from SENTRY Antimicrobial Resistance Surveillance Centers worldwide, 1998.

We reviewed Staphylococcus aureus bloodstream infection isolates from SENTRY centers worldwide during 1998 to evaluate the molecular epidemiology of multiply drug-resistant methicillin (oxacillin)-resistant S. aureus (MDR-MRSA). MDR-MRSA was defined as a S. aureus isolate with a MIC for oxacillin at >2 microg/ml and with four or more additional resistances. A total of 325 unique patient isolates of MDR-MRSA from five continents were analyzed using ribotyping and pulsed-field gel electrophoresis (PFGE). The frequency of MDR-MRSA among all S. aureus BSI isolates ranged from only 2.2% in Canada to 35.6% in the Asia-Pacific region. Forty-eight ribotypes (RT) were distinguished, but over 80% of the isolates were contained within the 10 most prevalent RTs. The most common RT, RT 184.5, which included 30% of all MDR-MRSA, was found on four of five continents. PFGE provided superior discrimination and identified numerous clusters of possible clonal dissemination of MDR-MRSA within individual medical centers and between institutions that are in geographic proximity. In four instances, strains with indistinguishable PFGE patterns were found on more than one continent. The predominant PFGE subtype in South America (RT 893.5/Ia) was isolated from patients at centers in Brazil, Argentina, and Portugal, and closely related subtypes were isolated in Chile and Italy. There is great geographic variation in rates of methicillin- and multidrug-resistance among S. aureus bloodstream isolates worldwide. Although many MDR-MRSA strains group geographically, a few closely related epidemic strains have wide regional and even global range.

Anti-Bacterial Agents↗

PubMed1993

[In vitro effects of combinations of antibiotics against highly-fosfomycin-resistant, methicillin-resistant Staphylococcus aureus. With special reference to efficacies of combinations of imipenem/cilastatin and cephems].

The author evaluated in vitro effects of combinations of antibiotics against 27 clinical isolates of highly-fosfomycin (FOM)-resistant, methicillin-resistant Staphylococcus aureus (MRSA). In combinations of FOM and cephems (CEPs), MICs of CEPs were decreased by FOM significantly, and synergistic effects were observed when the MIC of FOM was below 50 micrograms/ml. Combinations of imipenem/cilastatin (IPM/CS) and CEPs, however, was superior to those of FOM and CEPs in terms of synergistic effects. In these combinations, good synergism was found when the MIC of IPM/CS was below 25 micrograms/ml and those of CEPs were relatively low. In combinations of aminoglycoside and CEPs, no apparent synergism was observed. Most significant synergistic effect was achieved in the combination between IPM/CS and cefamandole. We believe that both fractional inhibitory concentration indices and achievement rates of effective serum concentrations should be taken into account to determine an effective combination of antibiotics.

Cephalosporins↗

PubMed1997

Investigation of nosocomial infection caused by arbekacin-resistant, methicillin-resistant Staphylococcus aureus.

An outbreak of coagulase VII-producing, arbekacin (ABK)-resistant, methicillin-resistant Staphylococcus aureus (MRSA) occurred between September 1994 and December 1995, involving five different wards. Twenty-one patients developed skin, wound, drainage, or respiratory tract colonization with coagulase VII-producing, (ABK)-resistant MRSA. Phenotypic characteristics (production of enterotoxin and TSST-1, antimicrobial susceptibility) and molecular-typing procedure (plasmid DNA profile, pulsed-field gel electrophoresis [PFGE] and arbitrarily primed polymerase chain reaction [AP-PCR] of chromosomal DNA) in isolated strains were compared. Plasmid analysis identified four different profiles and 19 of 22 strains recovered had identical patterns. PFGE of chromosomal DNA identified three different subtypes and 18 (81.8%) isolates shared the same subtype. AP-PCR also demonstrated that most strains had the same phenotypic characteristics. Although traditional epidemiological methods; for example, coagulase typing, plays a central role in hospital infection control, combination of plasmid DNA profile, AP-PCR, and PFGE may prove to be a particularly informative means of tracking the nosocomial spread of MRSA.

Adult↗

PubMed1990

Ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus in New York health care facilities, 1988. The New York MRSA Study Group.

The emergence in 1988 of ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus (MRSA) in New York City was studied in nine hospitals and eight nursing homes. Of the 43 hospitalized patients studied, 21 were admitted from home, while nine of the 12 nursing home patients were transferred from a hospital. Twenty-four of the 55 patients had been treated previously with ciprofloxacin, and 26 had an identifiable risk factor for a nosocomial infection. MRSA was a contributing factor in at least five of the 21 deaths. MRSA resistance to ciprofloxacin was detected within three months of the drug's commercial availability, apparently emerged independently at a number of the health care facilities, and has become widespread. If such resistance is found in a health care facility, ciprofloxacin may not be useful as a first line antibiotic.

Adult↗

PubMed1984

Subinhibitory concentrations of imipenem induce increased resistance to methicillin and imipenem in vitro in methicillin-resistant Staphylococcus aureus.

Methicillin-resistant (MR) Staphylococcus aureus that was susceptible to less than 0.75 micrograms of imipenem per ml demonstrated inducible resistance. MR S. aureus preincubated with 0.05 microgram of imipenem per ml grew in medium with an imipenem concentration of 32 micrograms/ml, and methicillin MICs increased 20-fold. Non-MR S. aureus exhibited no induction. Preincubation with methicillin produced no effect. Induction appeared to be a unique interaction of imipenem with MR S. aureus.

Enzyme Induction↗

PubMed1997

Enterotoxin and toxic shock syndrome toxin-1 production of methicillin resistant and methicillin sensitive Staphylococcus aureus strains.

In this study the production of enterotoxin A-D and toxic shock syndrome toxin-1 (TSST-1) of 181 methicillin resistant (MRSA) and 100 methicillin sensitive (MSSA) Staphylococcus aureus first isolates from different patients was investigated. All the MRSA- and MSSA isolates in the study were collected in a period between 1993 and 1995 from specimens sent from 11 different acute care hospitals in the greater Düsseldorf area. As far as possible the isolates were matched according to ward and hospital. The isolates were collected in the same time period and matched for specimen from which isolated. Furthermore, only first isolates were analysed in both groups. No significant difference in the production of toxin of any type between MRSA and MSSA could be detected (51 and 40% respectively). When the individual toxins were analysed, again no significant difference between MRSA and MSSA was demonstrable (enterotoxin production by MRSA 40% and MSSA 36%, and TSST-1 16% and 8% respectively). Despite this, a slight tendency for MRSA to produce enterotoxin A and B and for MSSA to produce enterotoxin C was observed. In addition, generation of TSST-1 by both groups was independent of enterotoxin A-D production. Interestingly, no increase in the proportion of TSST-1- or enterotoxin-producing MRSA and MSSA isolates was observed in strains isolated from blood cultures from patients with a clinical diagnosis of sepsis. Genotypical pulsed-field-gel-electrophoresis (PFGE) and phenotypical (bacteriophage typing, lysotyping) characterization of the 181 MRSA isolates resulted in 28 different PFGE patterns (of which 19 were toxin producers) and 22 lysotyping groups (18 of which produced toxin). In summary, the investigated clinical S. aureus isolates showed no difference in their ability to produce toxin and this was independent of their sensitivity to methicillin.

Bacterial Toxins↗

PubMed2003

[Pulsed-field gel electrophoresis type and antimicrobial susceptibility of arbekacin mupirocin and teicoplanin resistant methicillin-resistant Staphylococcus aureus].

Among the isolates of methicillin resistant Staphylococcus aureus (MRSA) which were isolated at Juntendo University Hospital between 1992 and 1998, there were 2 arbekacin resistant strains, 9 mupirocin resistant strain and 7 teicoplanin resistant strains. For each resistant strain, we studied pulsed-field gel electrophoresis (PFGE) pattern, coagulase type, antimicrobial susceptibility pattern and investigated a distribution of the resistant strains at the hospital wards. Two arbekacin resistant strains showed PFGE type A (A3 and A7, respectively). Nine mupirocin resistant strains were type C1; 3 strains, type A (A1, A4, A8); 3 strains and type D, E, G for 1 one each strain. The antimicrobial susceptibility pattern was not similar to each other and the strains were isolated from different year. It is suggested that these strains were not same origin. Seven teicoplanin resistant strains had PFGE type B (B1; 5 strains, B2/B5; 1 each strain). The antimicrobial susceptibility pattern of the strains was similar to each other and the strains were isolated from the same hospital ward between 1995 and 1997. From the above fact, the resistant strains appear to be hospital strains which have same origin.

Anti-Bacterial Agents↗

PubMed1998

Levofloxacin selects fluoroquinolone-resistant methicillin-resistant Staphylococcus aureus less frequently than ciprofloxacin.

Seventeen methicillin-resistant Staphylococcus aureus (MRSA) with unique genotypes were examined to determine if resistance occurs more frequently with ciprofloxacin or levofloxacin. The mean single-step resistance rate to 4 x MIC of ciprofloxacin was 1.05 x 10(-5) (range <4.82 x 10[-11] to 5.06 x 10[-5]), and that to levofloxacin was 4.03 x 10(-6) (range <3.57 x 10[-13] to 4.10 x 10[-5]) (P < 0.05). When serially passaged, the mean MICs of ciprofloxacin and levofloxacin increased 3.0 +/- 1.5-fold and 1.8 +/- 1.4-fold, respectively (P < 0.05). Only four strains became resistant to levofloxacin, but eight became resistant to ciprofloxacin (P < 0.05). Ciprofloxacin selects resistant MRSA more frequently than levofloxacin.

Anti-Infective Agents↗

PubMed1998

Intercontinental spread of a multidrug-resistant methicillin-resistant Staphylococcus aureus clone.

Two hundred ten methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered between 1990 and 1997 from three Portuguese hospitals located in Lisbon and Oporto were analyzed by molecular fingerprinting techniques. The hybridization of ClaI restriction digests with the mecA- and Tn554-specific DNA probes combined with pulsed-field gel electrophoresis documented the abrupt appearance and extensive intrahospital spread of the Brazilian epidemic MRSA clone in the 1995 samples of each one of the three hospitals analyzed-suggesting the intercontinental transfer of this strain from Brazil to Portugal. The appearance of this clone may challenge the dominance of another highly epidemic imported clone-the Iberian MRSA, currently the most widely spread MRSA clone in Portuguese hospitals.

Brazil↗

PubMed1994

[A study on the resistance of methicillin resistant Staphylococcus aureus to antimicrobial agents].

The morbidity of the infections caused by methicillin resistant staphylococcus aureus increased in recent years. In order to know the resistance of MRSA to antimicrobial agents, the minimal inhibitory concentrations (MICs) of antimicrobial agents against S. Aureus isolated from inpatients were measured. The presence of beta-lactamase in and the types of coagulase of the strains tested were determined as well. The results showed that MRSA accounted for 50.7% of the strains tested, the incidence of MRSA producing beta-lactamase was 85.1% and the coagulase of MRSA was all of type II. MRSA showed resistance to most of the lactam antibiotics and some of the aminoglycosides. Vancomycin and arbikacin had the highest activity against MRSA; other effective antibiotics were in the following order: amikacin, minocycline, tosulfloxacin and imipenem. It is suggested that serious infections caused by MRSA may be cured by using vancomycin, arbikacin or other antibiotics mentioned above.

Aminoglycosides↗