Int J Oral Maxillofac Implants, 2001 Mar-Apr, 16(2), 201 - 7 Early implant failures in patients treated with Brånemark System titanium dental implants: a retrospective study; Kronstrom M et al.; Implant failure has been associated with factors such as poor bone quality, insufficient bone volume, implant instability, unfavorable implant loading, and smoking habits . Infections and host responses may also be important factors in dental implant failure . The objectives of the present study were to identify various explanatory factors associated with titanium implant failure . Forty subjects with stage 1 non-osseointegrated titanium dental implants (NOTI) ad modum Branemark and 40 age- and gender-matched control subjects with successfully osseointegrated titanium implants (SOTI) were studied . Clinical data and gamma G immunoglobulin (IgG) antibody titers were studied . An independent t test revealed that significantly longer implants were placed in subjects with SOTI (P < .05) . Statistically significant differences in bone shape and resorption (BSR) scores were found between SOTI and NOTI (P < .05) . Logistic regression analysis identified 3 significant explanatory outcome variables: serum antibody avidity scores for Bacteroides forsythus (P < .0001), serum antibody titers to Staphylococcus aureus (P < .001), and the BSR scores (P < .05) . Antibody avidity to B forsythus and antibody titer to S aureus were therefore the 2 most important factors associated with early implant failures and with a significant predictive ability . This indicates that immunologic factors are involved in osseointegration. Eur J Biochem, 2001 May, 268(9), 2558 - 65 Human placental calreticulin characterization of domain structure and post-translational modifications; Hojrup P et al.; The domain organization and the post-translational modifications of human placenta calreticulin were analysed by MS in combination with proteolytic digestion . Prolonged treatment with trypsin, chymotrypsin, elastase, Staphylococcus aureus V8 protease, or proteinase K all led to a 6- to 7-kDa decrease in the molecular mass of calreticulin . The decrease was found to be due to cleavages in the region around residue 340 . In addition, minor fragments resulting from secondary cleavages close to the N-terminus were observed, but no stable fragments of intermediate size were found . These results show that the C-domain of calreticulin is susceptible to proteolytic cleavage and that the N- and P-domains form a proteolytically stable tight association . A disulfide bridge between the first two cysteines was mapped in the N-domain, and the third cysteine was found in the reduced form . No post-translational modifications in the form of glycosylation or phosphorylation were found . A modified form of calreticulin lacking the C-terminal hexapeptide including the KDEL endoplasmic reticulum retention sequon was isolated . Such a truncation may point to a mechanism that allows escape of calreticulin from the endoplasmic reticulum. Nippon Koshu Eisei Zasshi, 2001 Mar, 48(3), 190 - 9 {A study on the transmission of MRSA among the family members including clients of visiting nurse and related infection control}; Matsumoto K et al.; PURPOSE: The purpose of the study was to clarify MRSA (methicillin-resistant Staphylococcus aureus) transmission among clients, receiving nursing care from visiting nurse stations, and family members, as well as to determine MRSA positive rates of visiting nurses themselves and their handwashing habits . METHODS: The subjects were 131 clients who had utilized 32 visiting nurse stations, and had tested MRSA positive in our previous study performed 2-5 months earlier . The presence of MRSA in the nasal passages was investigated in 15 of the 131 MRSA positive clients and the 24 family members who had agreed to cooperate . Antibiotic sensitivity tests of the involved strains of MRSA were conducted using 14 antibiotics to allow antibiotic resistance patterns to be compared . 148 nurses who worked at 18 visiting nurse stations were also screened for MRSA in their nasal passages . In addition, a self-administered questionnaire was filled in concerning their handwashing habits . RESULTS: Out of 15 clients from whom MRSA was isolated in the previous study, 9 became MRSA positive (60.0%), and this was the case for 6 family members, living with 4 of them . The antibiotic resistance patterns coincided among the family members of 3 families, suggesting MRSA transmission among the client and his/her family member(s) . MRSA transmission was shown not to be influenced by the ADL (activities of daily living) of a client nor by the content or time of the care provided by family member(s) . As for visiting nurses, MRSA was isolated from 1 out of 148 (detection rate: 0.7%) . The practice rate for handwashing was 91.2% after visiting as compared to 22.1% before visiting, and 93.4% after care as compared to 37.5% before care; the differences were significant (P < 0.001) . The most frequently used handwashing procedures included handwashing with soap, povidone iodine and other disinfectants . The practice rate were 94.9% in visiting nurse stations and 91.2% in clients' homes . There was no significant difference between the procedures in these settings . DISCUSSION: Family members who are living with MRSA carriers are in danger of MRSA transmission irrespective of the content of the care, suggesting the need to prevent spread into compromised hosts or the community . On the other hand, visiting nurses are seldom infected with MRSA, and transmission of MRSA from nurses to clients is a rare event . This study showed, however, a low rate of handwashing before client contact . The possibility of cross infection from the hands of visiting nurses to their clients therefore needs further study. J Mol Microbiol Biotechnol, 2001 Apr, 3(2), 163 - 70 Staphylococcal multidrug efflux protein QacA; Brown MH et al.; The QacA multidrug exporter from Staphylococcus aureus mediates resistance to a wide array of monovalent or divalent cationic, lipophilic, antimicrobial compounds . QacA provides resistance to these various compounds via a proton motive force-dependent antiport mechanism that conforms to classical Michaelis-Menten kinetics . Fluorescent transport analyses have demonstrated that this QacA:substrate interaction occurs with high affinity and competition studies have shown that QacA-mediated ethidium export is competitively inhibited by other monovalent cations, and non-competitively inhibited by divalent cations, suggesting that monovalent and divalent cations bind at distinct sites on the QacA protein . The closely related export protein QacB, mediates lower levels of resistance to divalent cations, and lacks a high affinity-binding site for divalent cations . The cell membrane has been identified as the origin of QacA-mediated efflux; substrates are bound and expelled from within this hydrophobic environment . Regulation of qacA expression is achieved via the transacting repressor protein, QacR . QacR belongs to the TetR family of transcriptional repressor proteins, which all possess a helix-turn-helix DNA-binding domain at their N-terminal ends, and have highly divergent C-termini postulated to be involved in the binding of inducing compounds . QacR specifically binds to an inverted repeat, IR1, which has been identified as the qacA operator region, and overlaps the identified promoter sequence for qacA . QacR, like the multidrug export protein whose expression it regulates, has been shown to interact directly with a number of structurally-dissimilar compounds. Microbiology, 2001 May, 147(Pt 5), 1259 - 66 zur: a Zn(2+)-responsive regulatory element of Staphylococcus aureus; Lindsay JA et al.; A putative operon encoding a probable zinc-responsive regulatory element (zur) and components of an ABC-type transporter (mreA mreB) have been characterized in Staphylococcus aureus . The zur gene was inactivated but apparently this did not alter Zn(2+) uptake . Expression of mreAB zur is at a low level under a range of ion conditions . To allow inducible expression of the operon, a construct was made placing it under the control of the IPTG-inducible P(spac) promoter . Using this approach, it was shown that zur is able to repress expression of the entire operon in a Zn(2+)-dependent manner, and that mreA and mreB are likely to be involved in high-affinity ion uptake . zur has no apparent role in pathogenicity in a lesion model of S . aureus infection. Cell Biol Int, 2001, 25(4), 289 - 307 Measurement of fibroblast and bacterial detachment from biomaterials using jet impingement; Bundy KJ et al.; Fibroblast and Staphylococcus aureus detachment strength from orthopaedic alloys and a tissue culture plastic (Thermanox) have been investigated with jet impingement . For S . aureus, unlike fibroblasts, detachment is caused more by pressure than shear . For these biomaterials, detachment strength is much higher for S . aureus than fibroblasts . Comparing materials under equivalent flow conditions, S . aureus attach to stainless steel and titanium with equal strength and more strongly than to Thermanox . For fibroblasts, detachment strength from all materials was similar . Fibroblast detachment strength from these biomaterials substantially decreases with time at equal flow rates and increases with flow rate at equal exposure times . Detachment strength is very similar for 3T3 and L929 fibroblasts on Thermanox for equivalent flow rate/time combinations, though enhanced adhesion of 3T3 cells was often noted for metals . Time effects are less evident for S . aureus . S . aureus adhesion to metals is more affected by flow rate than fibroblast adhesion . Clin Infect Dis, 2001 May 15, 32(10), 1470 - 9 Epub 2001 Apr 18. Recurrent nonmenstrual toxic shock syndrome: clinical manifestations, diagnosis, and treatment; Andrews MM et al.; We report 3 cases of recurrent nonmenstrual toxic shock syndrome (TSS) and review the clinical manifestations, diagnosis, and treatment . The primary sites of infection were the genital tract (in a patient who underwent cesarean delivery), the upper respiratory tract, and a breast abscess . In all 3 patients, the initial illness was not recognized to be TSS; only after development of recurrent illness with desquamation was this diagnosis entertained . Strains of Staphylococcus aureus that were isolated from 2 patients produced TSS toxin-1, whereas the third strain produced staphylococcal enterotoxin B . All 3 patients lacked antibody to the implicated toxins at the time of presentation with recurrent illness . Nonmenstrual TSS can occur in a variety of clinical settings and may be recurrent . The presence of desquamation during a febrile, multisystem illness could suggest this diagnosis and should prompt the clinician to obtain appropriate cultures for S . aureus. Clin Infect Dis, 2001 May 15, 32(10), 1393 - 8 Epub 2001 Apr 20. Duration of colonization by methicillin-resistant Staphylococcus aureus after hospital discharge and risk factors for prolonged carriage; Scanvic A et al.; To investigate persistent carriage of methicillin-resistant Staphylococcus aureus (MRSA), we conducted a prospective 10-month study of MRSA carriage in previous carriers who were readmitted to our hospital . Four screening specimens, 2 from the skin and 2 from the nares, were obtained within 3 days after admission, in addition to diagnostic specimens requested by physicians . Of the 78 patients included in our study, 31 (40%) were persistent carriers of MRSA, with an estimated median time of 8.5 months to MRSA clearance . In the multivariate analysis, the only factor significantly associated with persistent carriage was the presence of a break in the skin at readmission (odds ratio, 4.34; P=.004); however, a trend was found for admission from a chronic-care institution (odds ratio, 3.65; P=.06) . Our data confirm that prolonged carriage of MRSA can occur after hospital discharge, support routine screening for MRSA at readmission of previously MRSA-positive patients, and suggest that a particularly high index of suspicion for MRSA carriage should be maintained if these patients have a break in the skin. Am J Ther, 2000 Sep, 7(5), 319 - 20 Vancomycin anaphylaxis in a patient with vancomycin-induced red man syndrome; Hassaballa H et al.; Vancomycin is a powerful glycopeptide antibiotic that is increasingly being used owing to the emergence of highly resistant organisms such as methicillin-resistant Staphylococcus aureus . Although a generally safe medication, administration of vancomycin is not benign, and there have been a number of adverse reactions reported . We present the case of a patient with vancomycin-induced red man syndrome who developed vancomycin anaphylaxis . Our case illustrates that red man syndrome may be a marker for true vancomycin allergy, although it was generally not thought of as so in the past. J Biol Chem, 2001 Jun 29, 276(26), 24360 - 4 Epub 2001 Apr 19. Human alveolar macrophages and granulocyte-macrophage colony-stimulating factor-induced monocyte-derived macrophages are resistant to H2O2 via their high basal and inducible levels of catalase activity; Komuro I et al.; Human alveolar macrophages (A-MPhi) and macrophages (MPhi) generated from human monocytes under the influence of granulocyte-macrophage colony-stimulating factors (GM-MPhi) express high levels of catalase activity and are highly resistant to H(2)O(2) . In contrast, MPhi generated from monocytes by macrophage colony-stimulating factors (M-MPhi) express low catalase activity and are about 50-fold more sensitive to H(2)O(2) than GM-MPhi or A-MPhi . Both A-MPhi and GM-MPhi but not M-MPhi can induce catalase expression in both protein and mRNA levels when stimulated with H(2)O(2) or zymosan . M-MPhi but not GM-MPhi produce a large amount of H(2)O(2) in response to zymosan or heat-killed Staphylococcus aureus . These findings indicate that GM-MPhi and A-MPhi but not M-MPhi are strong scavengers of H(2)O(2) via the high basal level of catalase activity and a marked ability of catalase induction and that catalase activity of MPhi is regulated by colony-stimulating factors during differentiation. Microb Pathog, 2001 Apr, 30(4), 247 - 52 Thrombin generation and mortality during Staphylococcus aureus sepsis; Bokarewa MI et al.; Sepsis-induced abnormalities of coagulation may contribute to mortality during severe bacterial infection . The aim of this study was to examine changes in coagulation parameters and to assess the role of protein C supplementation during murine S . aureus sepsis . Gram-positive sepsis was characterized by a hypercoagulable state with predominant activation of the external coagulation pathway, registered as an early increase of tissue factor activity and concomitant reduction in protein C . The internal coagulation pathway was unaffected . No correlation between the changes of coagulation parameters and the intensity of inflammation, determined as serum IL-6 levels, was found . Supplementation with neither protein C or APC favoured survival in S . aureus sepsis . Reduction in thrombin generation in response to protein C supplementation was associated with significantly increased survival . Microb Drug Resist, 2001 Spring, 7(1), 23 - 32 Molecular epidemiology of methicillin-resistant Staphylococcus aureus in Colombian hospitals: dominance of a single unique multidrug-resistant clone; Gomes AR et al.; The first study on the molecular characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates from Colombia was performed as part of a global surveillance established by the CEM/NET Initiative, under Project RESIST . Seventy-six MRSA isolates recovered from five hospitals during 1996-1998 were analyzed by the hybridization of ClaI restriction digests with mecA- and Tn554-specific probes, and by pulsed-field gel electrophoresis (PFGE) of chromosomal SmaI digests . All MRSA isolates, with one exception, belonged to a single clonal type II::NH::D . This clone, which was previously described among MRSA isolates recovered in the early 1990s in European and New York and South American hospitals, showed resistance to beta-lactam antibiotics only and appeared to be associated almost exclusively with pediatric infections ("Pediatric clone" of MRSA) . While sharing identical molecular typing properties with the Pediatric clone, the Colombian isolates differed by extensive multidrug resistance and were recovered from patients of all ages . It is also noteworthy that the Brazilian clone of MRSA (XI::B::B), another multidrug-resistant international clone currently widely spread in Brazil, Argentina, Uruguay, Chile, and also in several European countries, was completely absent from this set of isolates from Colombia. Infect Control Hosp Epidemiol, 2001 Mar, 22(3), 152 - 6 A blinded comparison of three laboratory protocols for the identification of patients colonized with methicillin-resistant Staphylococcus aureus; Gardam M et al.; OBJECTIVE: To compare three laboratory screening protocols for the detection of methicillin-resistant Staphylococcus aureus (MRSA) from surveillance specimens (mannitol-salt agar containing 2 microg/mL of oxacillin {MSA-2}, mannitol-salt agar containing 4 microg/mL of oxacillin {MSA-4}, and a broth-containing protocol as recommended by the American Society for Microbiology {M-ASM}) . DESIGN: Blinded comparative laboratory study and cost analysis . SETTING: University-affiliated microbiology laboratory . METHODS: Outcome measurements included rate of detection of MRSA-positive specimens and patients, turnaround time, and media and technologist costs . All MRSA culture swabs obtained from any patient site from November 1998 to April 1999 were included . RESULTS: The M-ASM protocol detected between 19.1% and 32.0% more MRSA-positive specimens and between 13.3% and 23.3% more MRSA-positive patients per surveillance event than the MSA-4 and MSA-2 protocols, respectively . There was no difference in positive-culture reporting time between the M-ASM and MSA4 protocols . The broth-containing protocol was 2- to 2.5-fold more expensive than the simpler protocols, taking into account media and laboratory personnel costs . CONCLUSIONS: It remains to be determined whether it is cost beneficial for a hospital to adopt the M-ASM, as the potential cost of MRSA transmission from unidentified MRSA-colonized patients is unknown . A broth-containing protocol should be considered the gold standard in future studies examining newer MRSA screening protocols Chem Pharm Bull (Tokyo), 2001 Apr, 49(4), 361 - 7 Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents . 3 . Synthesis and evaluation of 5-thiocarbamate oxazolidinones; Tokuyama R et al.; A series of 5-thiocarbamate oxazolidinones was prepared and tested for in vitro and in vivo antibacterial activities . The results of in vitro antibacterial activity indicated that the 5-thiocarbamate group was a suitable substituent for the activity by the 5-moderate hydrophilicity . The compounds within a favorable logP value range were found to have potent in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) . Compounds 3a and 4h were superior to linezolid in both in vitro and in vivo potency and were considered to be hopeful compounds . We also discuss the pharmacokinetic properties of several compounds in mice. Chem Pharm Bull (Tokyo), 2001 Apr, 49(4), 353 - 60 Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents . 2 . Relationship between lipophilicity and antibacterial activity in 5-thiocarbonyl oxazolidinones; Tokuyama R et al.; 5-Thiourea and 5-dithiocarbamate oxazolidinones were synthesized as a continuation of research on 5-thiocarbonyl oxazolidinone antibacterial agents considering the hydrophobic parameters of the molecule . The structure-activity relationship (SAR) study revealed that the antibacterial activity on 5-thiocarbonyl oxazolidinones was significantly affected by the lipophilicity, especially the calculated log P value and the balance between 5-hydrophilic (or hydrophobic) substituent and hydrophobic (or hydrophilic) substituents on the benzene ring . Some of 5-thiocarbonyl oxazolidinones were found to have good in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). J Assoc Physicians India, 2000 Nov, 48(11), 1057 - 9 Tropical pyomyositis: experience of a tertiary care hospital in north-west India; Malhotra P et al.; OBJECTIVE: Tropical pyomyositis (TP), a disease of varied aetiology, has been reported frequently from Africa and Latin America . However there are only a few reports from India . MATERIAL AND METHODS: Between January 1992 to June 1999, 26 patients with TP were admitted to Post Graduate Institute of Medical Education and Research Chandigarh, a tertiary care centre in north-west India and formed the study material . RESULTS: The disease was more common in young adults with male to female ratio being 5:2 . In majority, presenting features were muscle pains (100%) and fever (81%) . The diagnosis was confirmed by aspirating pus from the involved muscle . The pus grew organisms in 41.7% patients and methicillin sensitive Staphylococcus aureus was the commonest causative organism . Blood cultures were positive in 14.3% of cases . The common complications were bronchopneumonia (23.1%), empyema (19.2%) and venous thrombosis (15.4%) . In three patients, the disease occurred in association with tuberculosis of dorsal-lumbar spine . The overall mortality was low (7.7%) . CONCLUSIONS: TP is not an uncommon disease in India . Though the presenting features were similar to earlier studies, complications varied and mortality was low . An early recognition and aggressive treatment helps in decreasing morbidity and mortality. Mol Microbiol, 2001 Apr, 40(2), 433 - 9 Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus; Nagaev I et al.; Fusidic acid resistance resulting from mutations in elongation factor G (EF-G) of Staphylococcus aureus is associated with fitness costs during growth in vivo and in vitro . In both environments, these costs can be partly or fully compensated by the acquisition of secondary intragenic mutations . Among clinical isolates of S . aureus, fusidic acid-resistant strains have been identified that carry multiple mutations in EF-G at positions similar to those shown experimentally to cause resistance and fitness compensation . This observation suggests that fitness-compensatory mutations may be an important aspect of the evolution of antibiotic resistance in the clinical environment, and may contribute to a stabilization of the resistant bacteria present in a bacterial population. Acta Anaesthesiol Scand, 2001 May, 45(5), 570 - 5 Inhibitory effects of S-(-) and R-(+) bupivacaine on neutrophil function; Welters ID et al.; BACKGROUND: Local anesthetics inhibit migration, enzyme release and superoxide anion generation of polymorphonuclear leukocytes (PMN) . Due to their ability to phagocytose and kill bacteria PMN represent a major defense mechanism in the circulating blood . In this study we determined the influence of racemic bupivacaine and its enantiomers on neutrophil phagocytic activity, oxidative burst as well as surface expression of complement and Fcgamma receptors . METHODS: Venous blood was pre-incubated with different concentrations of either racemic bupivacaine, R-(+) or S-(-) bupivacaine . Fluoresceine isothiocyanate (FITC)-labeled antibodies against Fcgamma receptor III (CD16), complement receptor 1 (CD35) and complement receptor 3 (CD11b) were used to determine surface receptor expression . Phagocytic activity was measured by ingestion of FITC-labeled vital Staphylococcus aureus . Oxidative burst was determined by conversion of nonfluorescent dihydrorhodamine 123 into fluorescent rhodamine 123 . Fluorescent intensity of each sample was determined by flow cytometry . RESULTS: Racemic bupivacaine inhibited surface receptor expression, phagocytosis, and oxidative burst in a time- and concentration-dependent manner . Although the S-(-) enantiomer exerted significantly less inhibitory action on neutrophil function compared to R-(+) and racemic bupivacaine, these effects were small compared to the overall changes . CONCLUSION: These findings suggest that bupivacaine impairs surface receptor expression and may thereby contribute to reduced phagocytic activity and oxidative burst . Enantiomer-specific effects of bupivacaine may play a minor role in the inhibition of these leukocyte functions. J Food Prot, 2001 Apr, 64(4), 546 - 50 Survival of staphylococcus aureus and Escherichia coli as affected by ethanol and NaCl; Huang SL et al.; Growth of three strains of Staphylococcus aureus and two strains of Escherichia coli on nutrient agar (NA) supplemented with ethanol and NaCl was investigated . S . aureus did not grow on NA containing > or =10% ethanol (wt/wt) combined with > or =0% NaCl (wt/wt), or 7.5% ethanol combined with 7.5% NaCl . Neither E . coli nor E . coli O157:H7 grew on NA containing > or =7.5% ethanol combined with > or =0% NaCl, 5% ethanol combined with > or =2.5% NaCl, or > or =5% NaCl combined with > or =0% ethanol . It is apparent that NaCl enhanced the inhibitory effect of ethanol on growth of S . aureus and E . coli When cells were suspended in nutrient broth containing 12.5, 20, or 40% ethanol combined with NaCl, viable cells decreased with an increase of ethanol concentration . Ethanol sensitivity among strains and between genera varied in a limited range . When the cells were exposed to 20% ethanol in combination with 5% NaCl, S . aureus and E . coli lost viability after 30 and 10 min, respectively . When treated with 40% ethanol combined with > or =0% NaCl, all test strains lost viability within 5 min. J Food Prot, 2001 Apr, 64(4), 470 - 5 Antimicrobial edible packaging based on cellulosic ethers, fatty acids, and nisin incorporation to inhibit Listeria innocua and Staphylococcus aureus; Coma V et al.; Edible cellulosic films made with hydroxypropylmethylcellulose (HPMC) have proven to be inadequate moisture barriers . To improve its water vapor barrier properties, different hydrophobic compounds were incorporated into the HPMC matrix . Some fatty acids and derivatives were included into the film-forming solution prior to film formation . Stearic acid was chosen because of its high capacity to reduce significantly the water vapor transmission rate . Antimicrobial activity of edible HPMC film was obtained by the incorporation of nisin into the film-forming solution . Nisin is an antimicrobial peptide effective against gram-positive bacteria . The inhibitory activity of this bacteriocin was tested for inhibition of Listeria innocua and Staphylococcus aureus . The use of stearic acid was observed to reduce the inhibitory activity of active HPMC film against both selected strains . This phenomenon may be explained by electrostatic interactions between the cationic nisin and the anionic stearic acid . Further studies showed that antimicrobial activity of film varied with the nature of the hydrophobic compound incorporated, in decreasing order: film without lipid, methylstearate film, and stearic acid film . This corroborated the idea of electrostatic interactions. Chemotherapy, 2001 May-Jun, 47(3), 208 - 14 Bacterial adhesiveness: effects of the SH metabolite of erdosteine (mucoactive drug) plus clarithromycin versus clarithromycin alone; Braga PC et al.; After metabolization, erdosteine (a mucoactive drug) produces an active metabolite (Met I) with an SH group that is capable of opening disulphide bonds, including those of pilin, a protein of bacterial fimbriae . This induces stereochemical conformational changes that interfere with the binding of bacterial adhesins (fimbriae) to receptors on eukaryotic cells . At subinhibitory concentrations, the macrolide clarithromycin inhibits the expression of adhesins on bacterial cell surfaces . The addition of 5 and 10 microg/ml of Met I to 1/8, 1/16 and 1/32 MIC of clarithromycin potentiated the inhibition of Staphylococcus aureus adhesiveness to human mucosal cells in comparison with the antibiotic alone . This finding opens up a new possibility of interfering with bacterial adhesiveness and its resulting pathogenicity not only by using antibiotics but also by means of their combination with agents devoid of antibacterial activity . Eur J Clin Microbiol Infect Dis, 2001 Feb, 20(2), 117 - 9 Predisposing factors and outcome of Staphylococcus aureus bacteremia in neutropenic patients with cancer; Gonzalez-Barca E et al.; Staphylococcus aureus caused 30 of 438 (7%) cases of bacteremia in neutropenic patients with cancer during a 10-year study period . Acute leukemia as an underlying disease and severe oral mucositis were more frequent among patients with Staphylococcus aureus bacteremia (57% vs . 33%, P = 0.01, and 32% vs . 12%, P = 0.006, respectively) than among the 151 patients who had gram-negative bacteremia during the same study period . The most frequent source of Staphylococcus aureus bacteremia was the venous catheter (35% vs . 1%; P = 0.00001) . Septic metastases were more frequent in patients with Staphylococcus aureus bacteremia (14% vs . 4%, P = 0.03) . Attributable mortality was 10% and overall mortality 23% . Staphylococcus aureus bacteremia remains a significant cause of morbidity and mortality in neutropenic patients with cancer. J Eur Acad Dermatol Venereol, 2000 Sep, 14(5), 393 - 6 An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis; Faergemann J et al.; BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated by the presence of microorganisms and often responds well to treatment with potent corticosteroids . However, the long-term use of potent topical corticosteroids are accompanied by side-effects such as skin atrophy . OBJECTIVE: To study the effect and safety of prophylactic treatment with mometasone furoate fatty cream (contains hexylene glycol) for 6 months in patients with atopic dermatitis . RESULTS: Sixty-one of 68 (90%) patients were still free of their disease after 6 months of twice weekly treatment and only one showed possible treatment related signs of skin atrophy . The number of Staphylococcus aureus and Pityrosporum ovale were significantly reduced in cleared patients . CONCLUSIONS: Mometasone furoate fatty cream is effective and safe both for treatment and as a prophylaxis in patients with atopic dermatitis. Nippon Rinsho, 2001 Apr, 59(4), 728 - 32 {Clinical relevance of hetero-VRSA in surgical infections}; Okii K et al.; Vancomycin was used increasingly for treating methicillin-resistant Staphylococcus aureus(MRSA) infection . Recently MRSA strains which showed low-level resistance to vancomycin were isolated . Vancomycin-intermediate Staphylococcus aureus(VISA) show a vancomycin minimum inhibitory concentration(MIC) of 8 micrograms/ml . VISA appear to be rare . The vancomycin resistance phenotype is reported to be unstable in such isolates . To detect heterogeneously resistant VRSA(hetero-VRSA . MIC 1 to 4 micrograms/ml), we need to use population analysis and growth on Mu3 agar plate, because MIC cannot confirm hetero-VRSA . Hetero-VRSA is not so rare(about 0-47%) . Hetero-VRSA may be responsible for failure of vancomycin therapy, but its mechanism remains unclear . Until it becomes better understood, the clinical relevance cannot be assessed. Nippon Rinsho, 2001 Apr, 59(4), 666 - 72 {Mechanisms of methicillin and vancomycin resistance in Staphylococcus aureus}; Kuroda-Murakami H; The mechanism of methicillin and vancomycin resistance in Staphylococcus aureus (MRSA) is discussed, focusing on the phenotypic expression of resistance; i.e., pre-methicillin resistance, Egle-type resistance, heterogeneous and homogeneous resistance . Acquisition of staphylococcus cassette chromosome(SCCmec) by a recipient MSSA strain in the mecA-positive, and methicillin-susceptible status(pre-MRSA status) of S . aureus . Subsequent of the mecI-gene-mediated repression of mecA gene transcription results in the heterogeneous expression of methicillin resistance . It is only with the alternation of another chromosomal locus that the heterogeneous-to-homogeneous (hetero-to-homo) conversion of methicillin resistance occurs . Acquisition of a part of vancomycin-resistance(the level of hetero-VRSA) is associated with hetero-to-homo conversion of methicillin resistance, and full expression of vancomycin resistance(MIC = 8 mg/l) is achieved by additional acceleration of cell-wall synthesis causing apparent cell-wall thickening. Neurol India, 2001 Mar, 49(1), 41 - 6 Neuropathological complications of infective endocarditis : study of autopsy material; Patel FM et al.; 78 autopsy proven cases of infective endocarditis (IE) seen during 1983 to 1995 were retrospectively reviewed . The brain was available for examination in 44 cases . In the remaining cases, brain was not examined because examination of it was not requested due to lack of neurological findings . Brain lesions were observed in 35 out of 44 cases of IE . Assuming remaining 34 cases to be without brain lesions, the brain involvement in IE would be 44.87% (35 out of 78 cases) . Mean age of all cases of IE and those with brain lesions was similar i.e . 26.5+/-16.6 years and 26.6+/-13.06 years respectively . Largest number of cases with neuropathological lesions were associated with normal valve IE (48.57%) . Mitral valve was most commonly involved in cases with CNS complications (57.14%) (p<0.05) . The various types of brain lesions were infarction (68.57%), haemorrhage (57.14%), cerebral micro-abscess (31.42%) and focal meningitis (14.28%) . More than one type of lesion was observed in 19 cases, indicating complicated nature of brain lesions in fatal cases of IE . Left sided middle cerebral artery (MCA) territory was the commonest site of infarction and haemorrhage . Staphylococcus aureus appeared to be the most common organism in fatal cases of IE . Normal valve IE with or without CNS complications constitutes a significant group in India and is different from the west as far as the predisposing conditions are concerned. Antimicrob Agents Chemother, 2001 May, 45(5), 1535 - 8 Prolonged antimicrobial activity of a catheter containing chlorhexidine-silver sulfadiazine extends protection against catheter infections in vivo; Bassetti S et al.; The present study evaluated in vitro and in vivo a new chlorhexidine (C)-silver sulfadiazine (S) vascular catheter (the CS2 catheter) characterized by a higher C content and by the extended release of the surface-bound antimicrobials . The CS2 catheter was compared with a first-generation, commercially available CS catheter (the CS1 catheter) . The CS2 catheter produced slightly smaller zones of inhibition (mean difference, 0.9 mm {P < 0.001}) at 24 h against Staphylococcus aureus and five other microorganisms by several different methodologies . However, in a rabbit model, both CS catheters were similarly efficacious in preventing a catheter infection when the rabbits were inoculated with 10(4) to 10(7) CFU of S . aureus at the time of catheter insertion . The CS2 catheter retained its antimicrobial activity significantly longer in vitro and in vivo (half-lives exceeded 34 and 7 days, respectively) and was also significantly more efficacious in preventing a catheter infection when 10(6) CFU of S . aureus was inoculated 2 days after catheter implantation (P < 0.001) . These results suggest that prolonged anti-infective activity on the external catheter surface provides improved efficacy in the prevention of infection. Antimicrob Agents Chemother, 2001 May, 45(5), 1431 - 7 Mechanism and suppression of lysostaphin resistance in oxacillin-resistant Staphylococcus aureus; Climo MW et al.; The potential for the development of resistance in oxacillin-resistant Staphylococcus aureus (ORSA) to lysostaphin, a glycylglycine endopeptidase produced by Staphylococcus simulans biovar staphylolyticus, was examined in vitro and in an in vivo model of infection . Following in vitro exposure of ORSA to subinhibitory concentrations of lysostaphin, lysostaphin-resistant mutants were idenitifed among all isolates examined . Resistance to lysostaphin was associated with a loss of resistance to beta-lactams and a change in the muropeptide interpeptide cross bridge from pentaglycine to a single glycine . Mutations in femA, the gene required for incorporation of the second and third glycines into the cross bridge, were found following PCR amplification and nucleotide sequence analysis . Complementation of lysostaphin-resistant mutants with pBBB31, which encodes femA, restored the phenotype of oxacillin resistance and lysostaphin susceptibility . Addition of beta-lactam antibiotics to lysostaphin in vitro prevented the development of lysostaphin-resistant mutants . In the rabbit model of experimental endocarditis, administration of a low dose of lysostaphin for 3 days led predictably to the appearance of lysostaphin-resistant ORSA mutants in vegetations . Coadministration of nafcillin with lysostaphin prevented the emergence of lysostaphin-resistant mutants and led to a mean reduction in aortic valve vegetation counts of 7.5 log(10) CFU/g compared to those for untreated controls and eliminated the isolation of lysostaphin-resistant mutants from aortic valve vegetations . Treatment with nafcillin and lysostaphin given alone led to mean reductions of 1.35 and 1.65 log(10) CFU/g respectively . In ORSA, resistance to lysostaphin was associated with mutations in femA, but resistance could be suppressed by the coadministration of beta-lactam antibiotics. Antimicrob Agents Chemother, 2001 May, 45(5), 1323 - 36 Structural comparison of three types of staphylococcal cassette chromosome mec integrated in the chromosome in methicillin-resistant Staphylococcus aureus; Ito T et al.; The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S . aureus (MRSA) strain . We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world . There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec . However, new elements shared the chromosomal integration site with the SCCmec . Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec . The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec . Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome . Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome. J Am Geriatr Soc, 2001 Mar, 49(3), 270 - 6 Colonization of skilled-care facility residents with antimicrobial-resistant pathogens; Trick WE et al.; OBJECTIVES: To determine the frequency of and risk factors for colonization of skilled-care unit residents by several antimicrobial-resistant bacterial species, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), or extended-spectrum-beta-lactamase-producing (ESBL-producing) (ceftazidime resistant) Klebsiella pneumoniae or Escherichia coli . DESIGN: Point-prevalence survey and medical record review . SETTING: The skilled-care units in one healthcare facility . PARTICIPANTS: 120 skilled-care unit residents . MEASUREMENTS: Colonization by each of the four antimicrobial-resistant pathogens during a point-prevalence survey, using rectal, nasal, gastrostomy-tube site, wound, and axillary cultures, June 1-3, 1998; 117 (98%) had at least one swab collected and 114 (95%) had a rectal swab collected . Demographic and clinical characteristics were evaluated as risk factors for colonization . All isolates were strain typed by pulsed-field gel electrophoresis of total genomic deoxyribonucleic acid . RESULTS: Of 117 participants, 50 (43%) were culture positive for > or =1 antimicrobial-resistant pathogen: MRSA (24%), ESBL-producing K . pneumoniae (18%) or E . coli (15%), and VRE (3.5%) . Of 50 residents culture positive for any of these four antimicrobial-resistant species, 13 (26%) were colonized by more than one resistant species; only three (6%) were on contact-isolation precautions at the time of the prevalence survey . Risk factors for colonization varied by pathogen: total dependence on healthcare workers (HCWs) for activities of daily living (ADLs) and antimicrobial receipt for MRSA, total dependence on HCWs for ADLs for ESBL-producing K . pneumoniae, and antimicrobial receipt for VRE . No significant risk factors were identified for colonization by ESBL-producing E . coli . Among colonized patients, there was a limited number of strain types for MRSA (24 patients, 4 strain types) and ESBL-producing K . pneumoniae (21 patients, 3 strain types), and a high proportion of unique strain types for VRE (4 patients, 4 strain types) and FSBL-producing E . coli (17 patients, 10 strain types) . CONCLUSION: A large unrecognized reservoir of skilled-care-unit residents was colonized by antimicrobial-resistant pathogens, and co-colonization by more than one target species was common . To prevent transmission of antimicrobial-resistant pathogens in long-term care facilities in which residents have high rates of colonization, infection-control strategies may need to be modified . Potential modifications include enhanced infection-control strategies, such as universal gloving for all or high-risk residents, or screening of high-risk residents, such as those with total dependence on HCWs for ADLs or recent antimicrobial receipt, and initiation of contact-isolation precautions for colonized residents. J Intern Med, 2001 Apr, 249(4), 289 - 95 Specific T-cell receptor usage with cytokinemia in Henoch-Schönlein purpura nephritis associated with Staphylococcus aureus infection; Hirayama K et al.; OBJECTIVES: We sought to evaluate the mechanism of Henoch-Schonlein purpura nephritis (HSPN) associated with Staphylococcus aureus (S . aureus) infection . DESIGN: We evaluated six male patients with HSPN associated with S . aureus infection . Routine laboratory examinations, bacteriological examination, histological examination, and analysis of serum cytokine levels were performed in all cases . In addition, peripheral blood mononuclear cells (PBMC) obtained from the six patients and 45 normal individuals were stained with labelled-monoclonal antibodies against six variable parts of the beta-chain (Vbeta) of the T-cell receptor (TCR), and stained cells were analysed by flow cytometry . RESULTS: Patients with HSPN associated with S . aureus infection showed features of the nephrotic syndrome with rapidly progressive glomerulonephritis, as well as varying degrees of mesangial proliferative glomerulonephritis with crescent formation . Serological examination showed elevated levels of serum IgA and IgG as well as immune complexes after the onset of infection . The percentage of Vbeta-(5.2 + 5.3) and Vbeta 8-positive cells in patients with HSPN were significantly higher than in normal individuals; moreover, specific TCR-Vbeta usage was not observed in patients with HSPN whose S . aureus infection had improved . Serum levels of IL-1beta, IL-2, IL-6, IL-8 and TNF-alpha in patients with HSPN were significantly higher than in normal individuals, and normalized at the healing stage of S . aureus infection . CONCLUSION: Conventional antigens and/or staphylococcal enterotoxins originated from S . aureus might have been involved in the pathogenesis of HSPN in the present cohort . Therefore, steroid or other immunosuppressive therapies could not be utilized despite the high activity of glomerulonephritis, and as a result the prognoses of these cases of HSPN were serious. Clin Microbiol Infect, 2001 Feb, 7(2), 65 - 9 Uptake and intracellular activity of ketolide HMR 3647 in human phagocytic and non-phagocytic cells; Pascual A et al.; OBJECTIVE: To evaluate the uptake of HMR 3647 into human neutrophils (PMNs), human peritoneal macrophages (PMOs) and tissue-cultured cells (epithelial cells and fibroblasts), and to assess the intracellular activity of this drug . METHOD: Cell uptake of HMR 3647 was measured by radiometric assay, as described by Klemper and Styrt . Intracellular activity was determined by incubation for 3 h of PMNs containing bacteria in the presence of HMR 3647 . RESULTS: The intracellular concentrations were 130 and 71 times higher than extracellular concentrations in PMNs and PMOs, respectively (extracellular concentrations: 2-25 mg/L) . The cellular-to-extracellular concentration ratios (C/E) for tissue-cultured cells were lower than those obtained in phagocytic cells but still greater than 5 . The uptake of HMR 3647 was rapid and non-saturable in all cells . HMR 3647 was released slowly from phagocytic cells . HMR 3647 (extracellular concentration: 0.5-10 mg/L) did not significantly reduce the intracellular survival rate of Staphylococcus aureus ATCC 25923 in PMNs . CONCLUSIONS: HMR 3647 reaches intracellular concentrations several times higher than extracellular concentrations within phagocytic and non-phagocytic cells . The slow efflux of this drug from phagocytic cells suggests that these cells may be a vehicle for it, delivering it to sites of infection. Microbiol Res, 2001 Mar, 155(4), 345 - 9 Isolation and characterization of methicillin-resistant Staphylococcus aureus strains from nares of nurses and their gowns; Horikawa K et al.; The isolation and characterization of methicillin-resistant Staphylococcus aures (MRSA) strains from the bilateral nares of nurses and their gowns are described . MRSA strains could be isolated from eigth of fifty bilateral nares of nurses and two of their gowns . Ten MRSA strains were typed using coagulase typing, and divided into two types, coagulase II and III . In this study, we found a new group (producing toxic shock syndrome toxin -1, coagulase III and staphylococcal enterotoxin C) in Japanese MRSA . Furthermore, we confirmed that MRSA strains originating from bilateral nares of three nurses were identical and two strains isolated from the left naris of one nurse and her gown were also identical by pulsed-field gel electrophoresis. Microbiol Res, 2001 Mar, 155(4), 339 - 44 Characterization of hemolytic activity of Staphylococcus aureus strains isolated from bovine mastitic milk; Ali-Vehmas T et al.; Beta (beta) and delta (delta)-hemolysin of Staphylococcus aureus strains were cultured in vitro in milk lactoserum (whey) prepared from both healthy and mastitis bovine milk . Production of beta- and delta-hemolysins were detected in 12 out of 50 strains studied . The association between N-acetyl-beta-D-glucosaminidase (NAGase) activity, plasmin activity (PL) and trypsin inhibitory capacity (TIC), known as inflammatory indicators for mastitis, and hemolytic activity were also studied . Mastitic milk decreased directly the lytic effect of both beta-and delta-hemolysins of S . aureus on hemolytical blood agar plates . S . aureus in healthy milk samples produced more beta-hemolysin (3 times) and delta-hemolysin (2 times) when compared to S . aureus supernatants in milk from infected quarters . Furthermore, beta- and delta-hemolysis correlated negatively with TIC and NAGase and PL activities . Addition of reduced glutathione (GSH) or beta-mercaptoethanol into the artificial medium enhanced hemolysins activity. J Allergy Clin Immunol, 2001 Apr, 107(4), 607 - 14 Total and specific IgE in nasal polyps is related to local eosinophilic inflammation; Bachert C et al.; BACKGROUND: Nasal polyps (NPs) are characterized by eosinophilic inflammation and often coexist with asthma . However, the role of atopy and IgE in NP pathogenesis is unclear . OBJECTIVE: We sought to determine whether there is an association between total and specific IgE to a variety of allergens in polyp and nonpolyp tissue and markers of eosinophilic inflammation or skin test results . METHODS: Homogenates were prepared from nasal tissue of 20 patients with NPs and 20 patients without NPs and analyzed for concentrations of IL-5, IL-4, eotaxin, leukotriene (LT) C4/D4/E4, sCD23, and histamine (ELISA) . Eosinophil cationic protein (ECP), tryptase, and total and specific IgE for inhalant allergens and Staphylococcus aureus enterotoxins were measured (ImmunoCAP) . RESULTS: The concentrations of total IgE, IL-5, eotaxin, ECP, LTC4/D4/E4, and sCD23 were significantly higher in NP tissue compared with nonpolyp tissue . Total IgE was significantly correlated to IL-5, ECP, LTC4/D4/E4, and sCD23 and to the number of eosinophils in NPs . On the basis of the presence of specific IgE antibodies in tissue, 3 NP groups were defined . NP group 1 demonstrated no measurable specific IgE, and NP group 2 selected specific IgE . The third group demonstrated a multiclonal specific IgE, including IgE to S aureus enterotoxins, a high total IgE level, and a high prevalence of asthma . CONCLUSIONS: These studies suggest that there is an association between increased levels of total IgE, specific IgE, and eosinophilic inflammation in NPs, which may be of relevance in the pathophysiology of nasal polyposis . Similarly, the presence of specific IgE to staphylococcal enterotoxins A and B also points to a possible role of bacterial superantigens. J Heart Lung Transplant, 2001 Apr, 20(4), 483 - 5 Bacterial endocarditis: a rare complication following orthotopic cardiac transplantation; Kunst H et al.; We describe a 46-year-old man who developed infective endocarditis, meningitis, sternal abscess, and infective cerebral emboli after cardiac transplantation . Staphylococcus aureus was the infective organism . We successfully managed the patient with flucloxacillin and fusidic acid to treat infection, and with prostacyclin for systemic embolization. Int J Antimicrob Agents, 2001 Apr, 17(4), 327 - 9, discussion 329-30 Staphylococcus aureus bacteriuria and surgical site infections by methicillin-resistant Staphylococcus aureus; Matsukawa M et al.; Surgical site infection (SSI) remains an important cause of morbidity among hospitalized patients . We reviewed 421 patients who underwent open urological operations between January 1993 and December 1997 in our institute . Group I consisted of 259 patients who received uncontrolled antimicrobial prophylaxis (AMP) between 1993 and 1995 . Group II consisted of 162 patients who received controlled AMP between 1996 and 1997 . In group II, penicillins or first to second-generation cephalosporins was used and the duration of use for these agents regulated according to the wound class of each operation . The operations with clean wounds showed the lowest rate of SSI in both groups; the operations with contaminated wounds showed the highest rate of SSI (32.0% in group I and 33.3% in group II) . There was no significant difference in the total rates of SSI between the two groups (P=0.216) . The most frequently isolated bacterial species was methicillin-resistant Staphylococcus aureus (MRSA), isolated in 73.3% of the cases in group I and in 93.3% in group II . There was no significant difference in the incidence of MRSA isolation between the two groups (P=0.114) . The controlled AMP could not lower the incidence of MRSA-induced SSIs . In SSI patients, 22.7% of group I and 35.7% in group II, had MRSA bacteriuria before operation . The prohibition of third-generation cephalosporins and shorter duration of AMP did not reduce the incidence of SSI induced by MRSA because MRSA was not the emerging microorganism but rather a resident in the urological ward . On the other hand, the total incidence of SSI did not increase after regulation of AMP . This finding suggests that older antibacterial agents can prevent infection, except those caused by resistant microorganisms such as MRSA . The effective counter-measure for the prevention of MRSA-induced SSI is needed. Vet Microbiol, 2001 May 21, 80(2), 131 - 8 Staphylococcus aureus associated with mammary glands of cows: genotyping to distinguish different strains among herds; Joo YS et al.; The hypothesis that strains of Staphylococcus aureus are more likely to be unique to a herd than common to several herds was tested . Herds (n=28) from nine geographic areas of Korea, with elevated milk somatic cell counts (>500000 cells/ml) were enrolled in this study . Mammary quarter milk samples were aseptically collected from all lactating cows (n=616) with at least three functional quarters . Milk was cultured and S . aureus isolates were typed using pulse field gel electrophoresis of DNA SmaI digests . A total of 181 cows were identified as having S . aureus intramammary infections . A total of 52 different types of S . aureus were identified and 34 (65.4%) were associated with a single herd . A total of 18 types of S . aureus were found in multiple herds; 14 types were found in two herds, and four types were found in three herds . Herds with 1, 2, 3, and more than 3 types, were: four (14.3%); eight (28.6%); nine (32.1%); and seven (25.0%) . The data indicate that the majority of strains were found in one herd only, and more than 90% were found in two or less herds, suggesting that strains of S . aureus are more likely to be restricted to a single herd, than found in multiple herds. J Biol Chem, 2001 Jun 29, 276(26), 24015 - 22 Epub 2001 Apr 09. Structure and mechanism of action of an indolicidin peptide derivative with improved activity against gram-positive bacteria; Friedrich CL et al.; Indolicidin, an antimicrobial peptide with a unique amino acid sequence (ILPWKWPWWPWRR-NH(2)) is found in bovine neutrophils . A derivative of indolicidin, CP10A, has alanine residues substituted for proline residues and has improved activity against Gram-positive organisms . Transmission electron microscopy of Staphylococcus aureus and Staphylococcus epidermidis treated with CP10A showed mesosome-like structures in the cytoplasm . The peptide at 2-fold the minimal inhibitory concentration did not show significant killing of S . aureus ISP67 (a histidine, uridine, and thymidine auxotroph) but did show an early effect on histidine and uridine incorporation and, later, an effect on thymidine incorporation . Upon interaction with liposomes, detergents, and lipoteichoic acid, CP10A was shown by circular dichroism spectroscopy to undergo a change in secondary structure . Fluorescence spectroscopy indicated that the tryptophan residues were located at the hydrophobic/hydrophilic interface of liposomes and detergent micelles and were inaccessible to the aqueous quencher KI . The three-dimensional structure of CP10A in the lipid mimetic dodecylphosphocholine was determined using two-dimensional NMR methods and was characterized as a short, amphipathic helical structure, whereas indolicidin was previously shown to have an extended structure . These studies have introduced a cationic peptide with a unique structure and an ability to interact with membranes and to affect intracellular synthesis of proteins, RNA, and DNA. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 327 - 32 Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus; Tenover FC et al.; Strains of Staphylococcus aureus with reduced susceptibility to glycopeptides have been reported from Japan, the United States, Europe, and the Far East . Although isolates with homogeneous resistance to vancomycin (MICs = 8 microg/mL) continue to be rare, there are increasing reports of strains showing heteroresistance, often with vancomycin MICs in the 1-4 microg/mL range . Most isolates with reduced susceptibility to vancomycin appear to have developed from preexisting methicillin-resistant S . aureus infections . Many of the isolates with reduced susceptibility to glycopeptides have been associated with therapeutic failures with vancomycin . Although nosocomial spread of the vancomycin-intermediate S . aureus (VISA) strains has not been observed in U.S . hospitals, spread of VISA strains has apparently occurred in Japan . Broth microdilution tests held a full 24 hours are optimal for detecting resistance in the laboratory; however, methods for detecting heteroresistant strains are still in flux . Disk-diffusion tests, including the Stokes method, do not detect VISA strains . The Centers for Disease Control and Prevention and other groups have issued recommendations regarding appropriate infection control procedures for patients infected with these strains. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 323 - 6 Molecular epidemiology of methicillin-resistant Staphylococcus aureus; Shopsin B et al.; Subtyping methicillin- resistant Staphylococcus aureus (MRSA) isolates and tracking nosocomial infections have evolved from phenotypic to genotypic approaches; most laboratories now depend on pulsed-field gel electrophoresis (PFGE) . We discuss the limitations of current image-based genotyping methods, including PFGE, and the advantages (including ease of entering data into a database) of using DNA sequence analysis to control MRSA infections in health-care facilities. Emerg Infect Dis, 2001 Mar-Apr, 7(2), 178 - 82 The changing epidemiology of Staphylococcus aureus? Chambers HF. Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community . The changing epidemiology of MRSA bears striking similarity to the emergence of penicillinase-mediated resistance in S . aureus decades ago . Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially. Bioorg Med Chem Lett, 2001 Apr 9, 11(7), 919 - 21 Synthesis and biological evaluation of benzo{b}naphthyridones, a series of new topical antibacterial agents; Tabart M et al.; We describe here the synthesis and biological evaluation of a series of benzo{b}naphthyridones, a new family of tricyclic antibacterial compounds that have a gram-positive spectrum of activity . RP60556A, one of the most potent of these compounds, is bactericidal against multiresistant cocci, especially multiresistant Staphylococcus aureus strains . Its physico-chemical and biological properties make it particularly suitable for topical antibacterial use. Acta Microbiol Pol, 2000, 49(3-4), 237 - 42 Effect of Staphylococcus aureus serine proteinase on the respiratory burst in phagocytic cells in vitro; Miedzobrodzki J et al.; The in vitro effects of the Staphylococcus aureus serine proteinase (SASP) on the respiratory burst of human blood mononuclear phagocytes and rat lung macrophages were investigated . The generation of reactive oxygen species (ROS), determined by means of luminol-based chemiluminescence, was stimulated by treatment with SASP in both types of the defense cells . Cell activation depended on the concentration of the enzyme and the response of monocytes was an order of magnitude stronger relative to macrophages . The chemiluminescence emission kinetics were different for both cell types and the maximum signal was achieved in approximately 3 and 17 min, respectively . In experiments involving further cell activation by latex particles, macrophages pretreated with various SASP concentrations reacted with enhanced ROS generation whereas for monocytes, the latex-induced chemiluminescence was weakened by the enzyme . The results concerning the modification of the phagocytic host cell activity by SASP suggest that this enzyme might play an important role in pathomechanisms of staphylococcal infections in vivo. Acta Pol Pharm, 2000 Nov, 57 Suppl, 117 - 9 Antimicrobial activity of selected non-antibiotics--activity of methotrexate against Staphylococcus aureus strains; Kruszewska H et al.; Some non-antibiotic drugs, e.g . cytostatics, anaesthetics or vasodilators may also show the antimicrobial activity . The aim of this study was to detect and characterise the antimicrobial activity expressed by selected non-antibiotic drugs analysed during state control performed in the Drug Institute . Over 60 drugs were randomly chosen from different groups . The surveillance study was performed on standard microbial strains: S . aureus ATCC 6538P, E . coli ATCC 8739, P . aeruginosa ATCC 15442 and C . albicans ATCC 10231 . It was found that the drugs listed below inhibited growth at least one of the examined strains: Acesan 0.075 tabl., Benuron 500 mg tabl., Chlorchex 0.5 aerosol, Methotrexat-Ebewe 500 mg amp., Naproxen 500 mg tabl., Nospa Forte 60 mg tabl., Platamine 50 mg amp., Platidiam 50 mg amp., Sensit 50 mg drag., Septofervex 2 mg tabl., Seractil 400 mg tabl., Sermion 4 mg amp., Sinemet 125 mg tabl., Tarproxen 500 mg tabl . and Zyban 150 mg tabl . It was interesting, that strong antimicrobial activity of methotrexate was limited to Staphylococcus aureus strain . Minimal inhibitory concentration of methotrexate was determined by agar dilution method with the use of 54 clinical S . aureus strains (MRSA-32 and MSSA-22) . For MSSA strains, MIC50 and MIC90 were 10 micrograms/ml and 20 micrograms/ml, respectively (range: 10-20 micrograms/ml) . For MRSA strains, MIC50 and MIC90 were 20 micrograms/ml and 100-> 100 micrograms/ml, respectively (range: 10-< 100 micrograms/ml). Crit Care Med, 2001 Apr, 29(4 Suppl), N128 - 34 Infection control measures to limit antimicrobial resistance; Warren DK et al.; Increasing antimicrobial resistance has resulted in a rapidly decreasing array of therapeutic options for infections in the critical care setting . Reports of reduced susceptibility to vancomycin in Staphylococcus aureus raise the possibility of patients being infected with a virulent pathogen for which most antibiotics are ineffective . Infection control methods to contain resistance, exclusive of antimicrobial restrictions, focus on surveillance to identify carriers of resistant organisms, prevention of nosocomial infections, adequate hand hygiene, isolation of patients who harbor resistant organisms, and the use of barrier techniques such as gowns and gloves . Surveillance using clinical isolates alone is inadequate for the identification of the majority of patients who carry resistant organisms . However, it is unclear what intensity of surveillance is needed to control the spread of these organisms in the intensive care unit in nonoutbreak situations . Attempts at eradicating carriage are often unsuccessful when there is extranasal colonization with methicillin-resistant S . aureus . Transmission of resistant organisms is primarily the result of transient contamination of healthcare workers' hands . Adequate handwashing, isolation of carriers, and barrier techniques are all necessary for containing resistance within the intensive care unit, however, compliance with these measures can be compromised by high staff turnover and heavy workload. Crit Care Med, 2001 Apr, 29(4 Suppl), N100 - 7 Antimicrobial management strategies for Gram-positive bacterial resistance in the intensive care unit; Schentag JJ; This article summarizes the current situation with Gram-positive infections, including the two primary consequences-failure to cure and resistance-relevant to the intensive care unit . The past few years have seen Enterococcus faecium resistance to vancomycin increase from 10% of strains to approaching 60% of strains in some centers . Failure is now so frequent that vancomycin can no longer be safely used . This has lead to use of two new antibiotics, quinupristin/dalfopristin (Synercid), first marketed in the United States in September 1999, and linezolid (Zyvox), which reached the U.S . market in May 2000 . Both of these agents are being used to treat culture-proven vancomycin-resistant E . faecium . The calculated areas under the inhibitory curve (AUIC) values of vancomycin, even when its minimal inhibitory concentration (MIC) is 4.0 microg/mL, show almost all vancomycin-resistant E . faecium have AUICs <125 . This explains failure, as well as the further selection of this bacteria into subpopulations with progressively higher MICs . Less well defined, but potentially an even greater problem, is the poor efficacy of vancomycin against multiresistant Staphylococcus aureus . Here, there is evidence of clinical failure in lower respiratory tract infection patients, but in most cases the MIC values of the organism have not risen to the point where AUICs are <125 . However, the minimum bactericidal concentration of this organism may be considerably higher than its MIC, and in other cases there may be a high inoculum effect or a protein-binding effect to explain the failure of vancomycin to kill multiresistant S . aureus . Besides the increasing use of the new agents, strategies to manage these two increasingly resistant Gram-positive infections include cephalosporin restriction, switch and streamlining when cultures come back from the lab, combination regimens, and cycling in selected intensive care units. Crit Care Med, 2001 Apr, 29(4 Suppl), N92 - 6 Evolving antimicrobial chemotherapy for Staphylococcus aureus infections: Our backs to the wall; Daum RS et al.; Staphylococcus aureus is responsible for many nosocomial and community-acquired infections . Its evolving resistance to traditional antimicrobial chemotherapy and emerging prevalence outside of the healthcare environment are serious concerns . This review of the changing epidemiology of methicillin-resistant S . aureus, the emergence of vancomycin (glycopeptide)-resistant isolates, and the mechanisms of resistance to beta-lactams and glycopeptides provides an update for clinicians regarding effective strategies for treatment. Crit Care Med, 2001 Apr, 29(4 Suppl), N82 - 6 Impact of Gram-positive resistance on outcome of nosocomial pneumonia; Bodi M et al.; Among Gram-positive pathogens, Staphylococcus aureus is the leading cause of death from nosocomial pneumonia . The bacterium developed progressive resistance to beta-lactams, and methicillin-resistant strains emerged in the 1980s . In consequence, vancomycin has become the drug of choice for treatment of this infection over the last decade, based on susceptibility tests and the serum antimicrobial levels recorded . However, half of the patients treated with vancomycin have died . In contrast, in patients receiving beta-lactams for pneumonia caused by methicillin-sensitive S . aureus, survival is the rule . These observations, together with the emergence of isolates with reduced susceptibility to glycopeptides, raised concern about the use of vancomycin as standard therapy for pneumonia caused by Gram-positive cocci . Maintaining tissue levels above minimal inhibitory concentration is vital to successful clinical outcome . Optimizing treatment focusing on this goal and new antimicrobials provide new opportunities to improve survival . (Crit Care Med 2001; 29{Suppl.}:N82-N86) Science, 2001 Apr 6, 292(5514), 114 - 6 A link between virulence and ecological abundance in natural populations of Staphylococcus aureus; Day NP et al.; Staphylococcus aureus is a major cause of severe infection in humans and yet is carried without symptoms by a large proportion of the population . We used multilocus sequence typing to characterize isolates of S . aureus recovered from asymptomatic nasal carriage and from episodes of severe disease within a defined population . We identified a number of frequently carried genotypes that were disproportionately common as causes of disease, even taking into account their relative abundance among carriage isolates . The existence of these ecologically abundant hypervirulent clones suggests that factors promoting the ecological fitness of this important pathogen also increase its virulence. Infect Immun, 2001 May, 69(5), 3120 - 7 Clumping factor A mediates binding of Staphylococcus aureus to human platelets; Siboo IR et al.; The direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis . We have previously described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain ISP479, with reduced ability to bind human platelets in vitro . When tested in an animal model of endocarditis, the PS12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization . We have now characterized the gene disrupted in PS12 and its function in platelet binding . DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two Tn551 insertions within the clumping factor A (ClfA) locus (clfA) . The first copy was upstream from the clfA start codon and appeared to have no effect on ClfA production . The second insertion was within the region encoding the serine aspartate repeat of ClfA and resulted in the production of a truncated ClfA protein that was secreted from the cell . A purified, recombinant form of the ClfA A region, encompassing amino acids 40 through 559, significantly reduced the binding of ISP479C to human platelets by 44% (P = 0.0001) . Immunoprecipitation of recombinant ClfA that had been incubated with solubilized platelet membranes coprecipitated a 118-kDa platelet membrane protein . This protein does not appear to be glycoprotein IIb . These results indicate that platelet binding by S . aureus is mediated in part by the direct binding of ClfA to a novel 118-kDa platelet membrane receptor. Infect Immun, 2001 May, 69(5), 2996 - 3003 Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus; Herbert S et al.; It has long been known that certain antibiotics, at subinhibitory concentrations, differentially inhibit the synthesis of alpha-hemolysin and other staphylococcal virulence factors . In this report, we show that subinhibitory clindamycin (SBCL) eliminates production of nearly all exoproteins by Staphylococcus aureus but has virtually no effect on cytoplasmic proteins . The effect was abolished by a gene conferring resistance to macrolides-lincosamides-streptogramin B, showing that differential inhibition of protein synthesis is responsible; remarkably, however, subinhibitory clindamycin blocked production of several of the individual exoprotein genes, including spa (encoding protein A), hla (encoding alpha-hemolysin), and spr (encoding serine protease), at the level of transcription, suggesting that the primary effect must be differential inhibition of the synthesis of one or more regulatory proteins . In contrast to earlier reports, however, we found that subinhibitory clindamycin stimulates synthesis of coagulase and fibronectin binding protein B, also at the level of transcription . agr and sar expression was minimally affected by subinhibitory clindamycin . These effects varied from strain to strain and do not seem to be responsible for the effects of subinhibitory clindamycin on the overall exoprotein pattern. Infect Immun, 2001 May, 69(5), 2872 - 7 Staphylococcus aureus fibronectin binding proteins are essential for internalization by osteoblasts but do not account for differences in intracellular levels of bacteria; Ahmed S et al.; Staphylococcus aureus is a major pathogen of bone that has been shown to be internalized by osteoblasts via a receptor-mediated pathway . Here we report that there are strain-dependent differences in the uptake of S . aureus by osteoblasts . An S . aureus septic arthritis isolate, LS-1, was internalized some 10-fold more than the laboratory strain 8325-4 . Disruption of the genes for the fibronectin binding proteins in these two strains of S . aureus blocked their ability to be internalized by osteoblasts, thereby demonstrating the essentiality of these genes in this process . However, there were no differences in the capacity of these two strains to bind to fibronectin or osteoblasts . Analysis of the kinetics of internalization of the two strains by osteoblasts revealed that strain 8325-4 was internalized only over a short period of time (2 h) and to low numbers, while LS-1 was taken up by osteoblasts in large numbers for over 3 h . These differences in the kinetics of uptake explain the fact that the two strains of S . aureus are internalized by osteoblasts to different extents and suggest that in addition to the fibronectin binding proteins there are other, as yet undetermined virulence factors that play a role in the internalization process. Eur Respir J, 2000 Dec, 16(6), 1152 - 7 Ventilator associated pneumonia: quality of nonbronchoscopic bronchoalveolar lavage sample affects diagnostic yield; Baughman RP et al.; The importance of predefined criteria for acceptable samples of respiratory therapists obtained lower respiratory samples were studied, using a nonbronchoscopic bronchoalveolar lavage (BAL) protocol for ventilated patients in the intensive care unit . Therapists were instructed and asked to follow guidelines for obtaining samples . Over one year, 219 samples were obtained by respiratory therapists . Of these, 115 were considered to be adequate samples using the following criteria: 60 mL of instilled volume, at least 5 mL of fluid aspirated, specimens sent for semiquantitative culture, a differential cell count of <5% bronchial epithelial cells . Overall, 52 samples grew one or more pathogen at >10,000 colony forming units (cfu).mL(-1) of BAL . The most common pathogen was Staphylococcus aureus (S . aureus) (11 samples), although Gram-negative bacilli were the single pathogen in 21 specimens . Of the 115 acceptable samples, 40 (35%) grew > or =1 pathogen at >10,000 cfu.mL(-1) . For the 80 not acceptable samples which were sent for appropriate culture, 12 (15%) grew >10,000 cfu.mL(-1) BAL . This difference was significant (Chi-squared=9.44, p<0.01) . Nonbronchoscopic bronchoalveolar lavage can be safely performed by respiratory therapists' . The authors recommend that a protocol be used to evaluate the quality of a bronchoalveolar lavage sample in the same manner sputum samples are screened prior to interpretation. J Immunol, 2001 Apr 15, 166(8), 5129 - 38 Fibronectin binding protein A of Staphylococcus aureus can mediate human T lymphocyte adhesion and coactivation; Miyamoto YJ et al.; The extracellular matrix protein fibronectin (FN) mediates the adhesion of bacteria as well as T lymphocytes . Mammalian cells express integrins alpha(4)beta(1) and alpha(5)beta(1) as the major FN-binding cell surface receptors . Bacteria such as Staphylococcus aureus, also express FN-binding receptors that are important for adherence to host tissue and initiation of infection . The S . aureus FN-binding protein, FnbpA, has been previously identified, and recombinant proteins that correspond to distinct functional regions of this protein have been made . Three recombinant truncated forms of FnbpA, rFnbpA(37-881), rFnbpA(37-605), and rFnbpA(620-881), were examined for effects on in vitro adhesion and coactivation of human T lymphocytes . These proteins, when coimmobilized with anti-CD3 mAb, activated T lymphocyte proliferation . The coactivation signal generated by the rFnbpA proteins required medium containing serum with FN . Furthermore, the costimulatory signal could be restored in FN-depleted serum when the rFnbpAs were preloaded with soluble FN . Monoclonal Ab blocking studies revealed that integrin alpha(5)beta(1) is the major receptor responsible for the rFnbpA costimulatory signal . Shear flow cell detachment assays confirmed that lymphocytes can bind to FN captured by the rFnbpA proteins . These results suggest that the S . aureus rFnbpA can interact with integrin alpha(5)beta(1) via an FN bridge to mediate adhesion and costimulatory signals to T lymphocytes. J Immunol, 2001 Apr 15, 166(8), 5108 - 14 LOX-1 supports adhesion of Gram-positive and Gram-negative bacteria; Shimaoka T et al.; Adhesion of bacteria to vascular endothelial cells as well as mucosal cells and epithelial cells appears to be one of the initial steps in the process of bacterial infection, including infective endocarditis . We examined whether lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), a member of scavenger receptor family molecules with C-type lectin-like structure, can support adhesion of Gram-positive and Gram-negative bacteria . Chinese hamster ovary-K1 (CHO-K1) cells stably expressing LOX-1 can support binding of FITC-labeled Staphylococcus aureus and Escherichia coli, which was suppressed by poly(I) and an anti-LOX-1 mAb . Adhesion of these bacteria to LOX-1 does not require divalent cations or serum factors and can be supported under both static and nonstatic conditions . Cultured bovine aortic endothelial cells (BAEC) can also support adhesion of FITC-labeled S . aureus, which was similarly suppressed by poly(I) and an anti-LOX-1 mAb . In contrast, binding of FITC-labeled E . coli to BAEC was partially inhibited by the anti-LOX-1 mAb, and poly(I) did not block FITC-labeled E . coli adhesion to BAEC, but, rather, enhanced it under a static condition . TNF-alpha increased LOX-1-dependent adhesion of E . coli, but not that of S . aureus, suggesting that S . aureus adhesion to BAEC may require additional molecules, which cooperate with LOX-1 and suppressed by TNF-alpha . Taken together, LOX-1 can work as a cell surface receptor for Gram-positive and Gram-negative bacteria, such as S . aureus and E . coli, in a mechanism similar to that of class A scavenger receptors; however, other unknown molecules may also be involved in the adhesion of E . coli to BAEC, which is enhanced by poly(I). J Immunol, 2001 Apr 15, 166(8), 4884 - 90 Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch dendritic cells; Iwasaki A et al.; We have recently demonstrated the presence of three populations of dendritic cells (DC) in the murine Peyer's patch . CD11b(+)/CD8alpha(-) (myeloid) DCs are localized in the subepithelial dome, CD11b(-)/CD8alpha(+) (lymphoid) DCs in the interfollicular regions, and CD11b(-)/CD8alpha(-) (double-negative; DN) DCs at both sites . We now describe the presence of a novel population of intraepithelial DN DCs within the follicle-associated epithelium and demonstrate a predominance of DN DCs only in mucosal lymphoid tissues . Furthermore, we demonstrate that all DC subpopulations maintain their surface phenotype upon maturation in vitro, and secrete a distinct pattern of cytokines upon exposure to T cell and microbial stimuli . Only myeloid DCs from the PP produce high levels of IL-10 upon stimulation with soluble CD40 ligand(-) trimer, or Staphylococcus aureus and IFN-gamma . In contrast, lymphoid and DN, but not myeloid DCs, produce IL-12p70 following microbial stimulation, whereas no DC subset produces IL-12p70 in response to CD40 ligand trimer . Finally, we show that myeloid DCs from the PP are particularly capable of priming naive T cells to secrete high levels of IL-4 and IL-10, when compared with those from nonmucosal sites, while lymphoid and DN DCs from all tissues prime for IFN-gamma production . These findings thus suggest that DC subsets within mucosal tissues have unique immune inductive capacities. J Hosp Infect, 2001 Apr, 47(4), 294 - 300 Emergence and spread of low-level mupirocin resistance in methicillin-resistant Staphylococcus aureus isolated from a community hospital in Japan; Watanabe H et al.; The objective of this study was to investigate the state of mupirocin resistance in methicillin-resistant Staphylococcus aureus (MRSA) in a community hospital in Japan . Ninety strains of MRSA were isolated from the respiratory tract of 56 patients (group I, Jun 1990-Aug 1996) before introduction of mupirocin in Japan, which were compared with 168 strains from 48 patients (group II, Sept 1996-Jan 1998) and 146 strains from 85 patients (group III, Feb 1999-Dec 1999) isolated after introduction of mupirocin . Comparisons were made by determining the minimum inhibitory concentrations (MIC) against nine antibiotics . Fifty-five MRSA isolates from 27 patients {13 (27.1%) of 48 in group II and 14 (16.5%) of 85 in group III} after introduction of mupirocin showed low-level resistance to mupirocin (MIC, 6.25 to 50 microg/ml) but the remaining isolates were sensitive to mupirocin (MIC < or =3.13 microg/ml) . Most patients colonized with low-level mupirocin-resistant MRSA were elderly (> or =65 years of age), on total parenteral nutrition or nasal feeding and had other underlying diseases . The proportion of patients colonized with low-level mupirocin-resistant MRSA following repeated use of mupirocin was higher in patients of group II than those of group III . Molecular typing by pulsed-field gel electrophoresis (PFGE) demonstrated that the pattern of 13 MRSA isolates from 13 patients of group II consisted of three patterns (A, B, C) with predominance of pattern A, while the pattern of 13 MRSA isolates from 13 patients of group III consisted of three patterns (A, C, D) with predominance of patterns A and D . Our results indicated that resistance of MRSA to mupirocin remains at a low level at present in Japan . However, we should be aware of the possible emergence of MRSA highly resistant to mupirocin in the future . J Korean Med Sci, 2001 Feb, 16(1), 39 - 44 Enhanced neutrophil functions by recombinant human granulocyte colony-stimulating factor in diabetic patients with foot infections in vitro; Peck KR et al.; This study was performed to evaluate the effect of granulocyte-colony stimulating factor on neutrophil functions in diabetic patients with active foot infections in vitro . Twelve diabetic patients with foot infections and 12 normal volunteers were enrolled . Neutrophils from peripheral blood were incubated with granulocyte colony-stimulating factor (G-CSF, 50 ng/mL) for 20 min . Superoxide production of neutrophils was measured by the reduction of ferricytochrome C . Neutrophil phagocytosis was assayed using Staphylococcus aureus and the weighted phagocytic index was calculated . Superoxide production of neutrophils in diabetic patients with foot infections was 7.7 (unit: nmol/2 x 10(5) cells/60 min), which was significantly lower than that in controls (12.0) (p<0.05) . G-CSF increased neutrophil superoxide production to 12.1 in diabetic patients with foot infections and to 19.8 in controls (p<0.05 for each) . Weighted phagocytic index in diabetic patients with foot infections was 0.77, which was not significantly different from that of the controls (0.69) . Weighted phagocytic index was increased significantly by G-CSF to 0.88 in diabetic patients with foot infections and to 0.79 in controls (p<0.05 for each) . In conclusion, G-CSF significantly enhanced neutrophil functions in diabetic patients with foot infections in vitro. J Nat Toxins, 2001 Feb, 10(1), 1 - 8 Genes encoding staphylococcal enterotoxins G and I are linked and separated by DNA related to other staphylococcal enterotoxins; Monday SR et al.; Fifteen randomly selected Staphylococcus aureus isolates, known to carry the staphylococcal enterotoxin (SE) G determinant (seg), were shown to carry the SEI determinant (sei) . To determine whether these two genes are linked, two S . aureus strains (FRI445 and FRI572), each containing the seg and sei determinants, were further analyzed . In these strains, sei is located 2,002 bp upstream of seg . Within the intergenic nucleotide sequence are three regions of nucleotide sequence with significant identity to the sequences of other SE genes . Characterization of the DNA regions surrounding the seg and sei determinants will allow a better understanding of the association between these two genes and may explain why they are so frequently observed simultaneously in S . aureus isolates. Med Dosw Mikrobiol, 2000, 52(4), 397 - 403 {The effect of selected factors on the course of wound healing after surgery for laryngeal neoplasms}; Jozefowicz-Korczynska M et al.; Finding of the a etiologic factors and participation of bacteria flora in wound healing in laryngeal cancer treatment was the purpose of our study . Investigations were performed in 27 patients . Swabs were taken from the postoperative wounds . Detailed identifications of the bacteria flora and antibiotic susceptibility of bacteria were performed . Wound healing was estimated according to extension of the carcinoma, applied antibiotics, state of the oral cavity, the kind of bacteriological flora isolated after surgical treatment from postoperative wounds . It was found that wound healing depended on the extension of carcinoma, as well as, type of isolated bacteria and antibiotic therapy used . The proper healing of postoperative wounds was not dependent on the state of the oral cavity and the dentition . The main cause of postoperative complication of wounds was methicillin-resistant Staphylococcus aureus (MRSA). Med Dosw Mikrobiol, 2000, 52(4), 327 - 32 {Evaluation of methicillin-resistance in Staphylococcus aureus by the agar disk diffusion method and PCR}; Idzik D et al.; Staphylococcus aureus is a widespread human pathogen . One the most striking characteritics of this bacterium is resistance to methicillin and all beta-lactam antibiotics . The agar disk diffusion method is the most widely used in vitro susceptibility test, but recently molecular methods, e.g . Polymerase Chain Reaction, have been also introduced . We compared the detection of methicillin resistant coagulase positive Staphylococcus aureus isolated from clinical materials in Silesian microbiological laboratories by diffusion method and PCR through the detection of nuc and mec A genes . Our results show that PCR used for the detection of mec A gene increases the detection of methicillin-resistant Staphylococcus aureus strains by 10% as compared to the agar disk diffusion method . Among Staphylococcus aureus strains, detected as methicillin-resistant, 17% of organisms showed no presence of mec A gene. Biochemistry, 2001 Apr 10, 40(14), 4426 - 36 Spectroscopic properties of the metalloregulatory Cd(II) and Pb(II) sites of S . aureus pI258 CadC; Busenlehner LS et al.; Staphylococcus aureus pI258 CadC is an extrachromosomally encoded metalloregulatory repressor protein from the ArsR superfamily which negatively regulates the expression of the cad operon in a metal-dependent fashion . The metalloregulatory hypothesis holds that direct binding of thiophilic divalent cations including Cd(II), Pb(II), and Zn(II) by CadC allosterically regulates the DNA binding activity of CadC to the cad operator/promoter (O/P) . This report presents a detailed characterization of the metal binding and DNA binding properties of wild-type CadC . The results of analytical ultracentrifugation experiments suggest that both apo- and Cd(1)-CadC are stable or weakly dissociable homodimers characterized by a K(dimer) = 3.0 x 10(6) M(-1) (pH 7.0, 0.20 M NaCl, 25.0 degrees C) with little detectable effect of Cd(II) on the dimerization equilibrium . As determined by optical spectroscopy, the stoichiometry of Cd(II) and Pb(II) binding is approximately 0.7-0.8 mol/mol of wild-type CadC monomer . Chelator (EDTA) competition binding isotherms reveal that Cd(II) binds very tightly, with K(Cd) = 4.3 (+/-1.8) x 10(12) M(-1) . The results of UV-Vis and X-ray absorption spectroscopy of the Cd(1) complex are consistent with a tetrathiolate (S(4)) complex formed by four cysteine ligands . The (113)Cd NMR spectrum reveals a single resonance of delta = 622 ppm, consistent with an S(3)(N,O) or unusual upfield-shifted S(4) complex . The Pb(II) complex reveals two prominent absorption bands at 350 nm (epsilon = 4000 M(-1) cm(-1)) and 250 nm (epsilon = 41 000 M(-1) cm(-1)), spectral properties consistent with three or four thiolate ligands to the Pb(II) ion . The change in the anisotropy of a fluorescein-labeled oligonucleotide containing the cad O/P upon binding CadC and analyzed using a dissociable CadC dimer binding model reveals that apo-CadC forms a high-affinity complex {K(a) = (1.1 +/- 0.3) x 10(9) M(-1); pH 7.0, 0.40 M NaCl, 25 degrees C}, the affinity of which is reduced approximately 300-fold upon the binding of a single molar equivalent of Cd(II) or Pb(II) . The implications of these findings on the mechanism of metalloregulation are discussed. Biochemistry, 2001 Apr 10, 40(14), 4312 - 22 Analysis of MDR1 P-glycoprotein conformational changes in permeabilized cells using differential immunoreactivity; Druley TE et al.; The reactivity of the ATP-dependent multidrug transporter P-glycoprotein (Pgp) with the conformation-sensitive monoclonal antibody UIC2 is increased in the presence of Pgp transport substrates, ATP-depleting agents, or mutations that reduce the level of nucleotide binding by Pgp . We have investigated the effects of nucleotides and vinblastine, a Pgp transport substrate, on the UIC2 reactivity of Pgp in cells permeabilized by Staphylococcus aureus alpha-toxin . ATP, ADP, and nonhydrolyzable ATP analogues decreased the UIC2 reactivity; this effect was potentiated by vanadate, a nucleotide-trapping agent . The Hill number for the nucleotide-induced conformational transition was 2 for ATP and ADP but 1 for nonhydrolyzable ATP analogues . The Hill numbers for ATP and ADP were decreased to 1 by mutations in one of the two nucleotide binding sites of Pgp, whereas mutation of both sites greatly diminished the overall effect of nucleotides . Vinblastine reversed the decrease in the UIC2 reactivity brought about by all the nucleotides, including nonhydrolyzable analogues; this effect of vinblastine was blocked by vanadate . These data indicate that UIC2-detectable conformational changes of Pgp are driven by binding and debinding of nucleotides, that nucleotide hydrolysis affects the Hill number for its Pgp interactions, and that Pgp transport substrates promote nucleotide dissociation from Pgp . These findings are consistent with a conventional E1/E2 model that explains conformational transitions of a transporter protein through a series of linked equilibria. Microbiology, 2001 Apr, 147(Pt 4), 803 - 10 The signal transducer (BlaRI) and the repressor (BlaI) of the Staphylococcus aureus beta-lactamase operon are inducible; Clarke SR et al.; The precise start points for transcription of the blaZ and of the blaRI/blaI genes of the Staphylococcus aureus beta-lactamase operon have been determined by primer extension analysis . Consequently the overlapping promoter sequences were deduced . Northern blots showed that the synthesis of the 2100 nt mRNA from blaRI is inducible and that a blaI probe hybridized to the same mRNA as the blaRI probe . The gene cat, encoding chloramphenicol acetyltransferase, was fused separately to the blaZ and blaRI/blaI promoters, and used to compare their strengths . The promoter for blaZ is about six times stronger than that for blaRI/blaI and the synthesis of chloramphenicol acetyltransferase from both promoters is inducible, supporting the results from the Northern blots. J Clin Microbiol, 2001 Apr, 39(4), 1669 - 71 Low Prevalence of Community-Acquired Methicillin-Resistant Staphylococcus aureus in Adults at a University Hospital in the Central United States; Suntharam N et al.; Community-acquired MRSA (CA-MRSA) is potentially a new emerging pathogen with most strains susceptible to many antimicrobials except for beta-lactam antibiotics . We retrospectively reviewed MRSA isolates during a 20-month study period (January 1998 through August 1999) and investigated those that were clindamycin susceptible . Patients were not considered to harbor CA-MRSA if they had been admitted to a hospital within the preceding 2 years or if their isolate had been obtained more than 72 h after admission . There were 2,817 S . aureus isolates, with 1,071 (38%) being MRSA . Of these 1,071 isolates, 161 were clindamycin susceptible; these were recovered from 81 patients . Of these 81 patients, 20 appeared to have community-acquired strains, but only 2 could be confirmed as having CA-MRSA. J Clin Microbiol, 2001 Apr, 39(4), 1540 - 8 Identification and characterization of phage variants of a strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-15); O'Neill GL et al.; EMRSA-15 is one of the most important strains of epidemic methicillin-resistant Staphylococcus aureus (EMRSA) found in the United Kingdom . It was originally characterized by weak lysis with phage 75 and production of enterotoxin C but not urease . Two variant strains of EMRSA-15 which show a broader phage pattern than the progenitor strain have emerged . A total of 153 recent clinical isolates representing classical EMRSA-15 (55 isolates) or these phage variants (98 isolates) were compared by SmaI macrorestriction profiles in pulsed-field gel electrophoresis (PFGE) as well as by urease and enterotoxin C production . Eight of the 98 isolates were shown to be other unrelated strains by both PFGE and their production of urease, a misidentification rate of 8% by phage typing . Seventy-one EMRSA-15 isolates were enterotoxin C negative, and the majority of these were sensitive to phage 81 . Examination of PFGE profiles and Southern blotting studies suggest that the enterotoxin C gene locus is encoded on a potentially mobile DNA segment of ca . 15 kb . After elimination of the eight non-EMRSA-15 isolates, the remaining 145 were characterized by PFGE, yielding 22 profiles . All profiles were within five band differences of at least one other profile . Classical EMRSA-15 isolates showed nine PFGE profiles, with the majority of isolates (68%) in profile B1 . Six of these nine PFGE profiles were unique to the classical EMRSA-15 isolates . Among the phage variants of EMRSA-15, 16 profiles were seen, but the majority of isolates (83%) fell into 1 of 4 profiles (B2, B3, B4, and B7) which correlated well with phage patterns . The most divergent PFGE profiles among the EMRSA-15 isolates had as many as 12 band differences from one another, suggesting that in examining isolates belonging to such a temporally and geographically disseminated epidemic strain, the range of PFGE profiles must be regarded as a continuum and analyzed by relating the profiles back to the most common or progenitor profile. Int J Pharm, 2001 Feb 19, 214(1-2), 93 - 8 Activity of mammalian secreted phospholipase A(2) from inflammatory peritoneal fluid towards PEG-liposomes . Early indications; Vermehren C et al.; Due to an increase in the activity of phospholipase A(2) (PLA(2)) in various inflammatory diseases, this enzyme may play a key role in the degradation of liposomes and the subsequent release of drug when PEG-liposomes passively target inflammatory tissue . The activity of mammalian secreted phospholipase A(2) (sPLA(2)) in casein stimulated peritoneal fluid was tested toward liposomes of different compositions . Early results indicate only a slight degradation of conventional dipalmitoylphosphatidylcholine (DPPC) liposomes as well as DPPC liposomes incorporated with different concentrations of PEG(2000) . However, the DPPC degradation increased to 7% when inclusion of 30 mol% phosphatidylethanolamine (PE) in the lipid bilayer . The increase in degradation may be due to an improvement of the substrate - as it is well known, that PE is a better substrate for the mammalian sPLA(2) than PC . Incorporation of PE into the bilayer may increase the binding properties of the bilayer resulting in improved conditions for the enzymatic attack by sPLA(2) . In addition, inhibitory zones of Staphylococcus aureus in an agar diffusion test showed that PLA(2) from Crotalus atrox venom was able to catalyze the release of gentamicin from PEG-liposomes . In conclusion, this study suggest that degradation of the lipid bilayer of PEG-liposomes by PLA(2) result in release of incapsulated drug, e.g . gentamicin and inclusion of PE in the liposomal bilayer, may enhance the activity of the mammalian sPLA(2) toward liposomes composed of DPPC. J Med Assoc Thai, 2001 Jan, 84(1), 63 - 8 Clinical features of septic arthritis of sternoclavicular joint; Akkasilpa S et al.; We studied 21 patients with septic arthritis of the sternoclavicular joint at Chulalongkorn University Hospital between January 1987 and January 1997 . There were 15 males (71.4%) and 6 females (28.6%) . The mean age was 47.4 years with a range of 16 to 69 . More than half of the patients (57.1%) were aged more than 50 years and most had associated diseases including diabetes mellitus and cirrhosis . Almost all of the younger age group had a history of intravenous drug abuse . All of the patients had fever and sternoclavicular joint pain . Most of the patients (66.7%) had monoarticular arthritis, whereas, the others had oligoarticular arthritis . Staphylococcus aureus was the most commonly or identified organism in the patients . Retrosternal abscess was seen by computerized tomography in 6 patients (28.6%) . All patients received parenteral antibiotics, and 5 patients (23.8%) required surgical drainage of a retrosternal abscess . Eighteen patients recovered but there were 3 (14.3%) deaths . All of these had retrosternal abscesses . The major cause of death was septic shock . Septic arthritis of the sternoclavicular joint is an uncommon disease in Thai clinical practice . Although uncommon, retrosternal abscess is a life threatening complication. Nihon Rinsho Meneki Gakkai Kaishi, 2001 Feb, 24(1), 48 - 56 {A boy diagnosed SLE after Staphylococcus aureus infection over a long period}; Wada Y et al.; We encountered a 13-year-old boy with SLE who showed specific pathophysiology . The affected child was hospitalized because of long-standing cutaneous empyesis considered to be Staphylococcus aureus infection, followed by manifestation of meningoencephalitis-like symptoms . On a close check up, the patient was diagnosed as having SLE complicated with interstitial lupus nephritis and verrucosis of the left ventricle . Besides the findings, the blastogenesis of the patient's lymphocyte was low against stimulation of sac-1 which connects with the Fc portion of lgG, one of the constituent proteins of Staphylococcus . Moreover, anti-phospholipid antibodies turned positive during immunosuppressive therapy and subcutaneous abscess due to Pseudomonas aeruginosae developed concurrently at about the same time, which posed difficulties in the treatment . The affected child had had Staphylococcus aureus infections over a long period of time before diagnosis of SLE and was susceptible to bacterial infections due to Pseudomonas aeruginosae during the treatment . The clinical course of this case was considered important in presuming the complex immunologically abnormal condition of SLE in childhood. Arch Intern Med, 2001 Feb 12, 161(3), 406 - 10 Single-lumen subcutaneous ports inserted by interventional radiologists in patients undergoing chemotherapy: incidence of infection and outcome of attempted catheter salvage; Kuizon D et al.; BACKGROUND: Subcutaneous ports are commonly used for vascular access in patients with cancer undergoing chemotherapy . OBJECTIVES: To determine the incidence of catheter-related infection and to assess the efficacy of catheter salvage in subcutaneous ports . METHODS: We retrospectively reviewed 300 subcutaneous single-lumen chest ports inserted by interventional radiologists in 294 patients between December 1, 1995, and November 15, 1997, at the Cleveland Clinic Foundation, Cleveland, Ohio . The number of days that the catheter remained in situ, infection rate, treatment, and outcome of infection were determined . RESULTS: Two hundred ninety-four patients had a total of 79 748 catheter-days . Vascular access for chemotherapy was the indication for 95% of the subcutaneous ports placed . Seventeen catheters (5.7%) developed 20 episodes of noninfectious complications resulting in the removal of 6 ports . Seventeen patients (5.7%) developed catheter-related infections (2.1/10 000 catheter-days) including 10 episodes of catheter-related bacteremia (1.2/10 000 catheter-days) . The most common organism isolated was Staphylococcus aureus . A total of 15 of the 17 infected catheters were removed . Salvage was attempted in 6 patients in whom 4 catheters were eventually removed due to recurrent bacteremia (2 patients) and persistent local infection (2 patients) . One of the 10 patients with catheter-related bacteremia developed septic arthritis . There were no complications associated with attempted catheter salvage . CONCLUSIONS: Subcutaneous single-lumen ports inserted by interventional radiologists in patients undergoing chemotherapy have low complication rates but infections remain the leading cause of catheter loss . Antibiotic therapy without catheter removal is unlikely to eradicate catheter-related bacteremia. Commun Dis Public Health, 2000 Dec, 3(4), 288 - 90 Infection of foot ulcers with Staphylococcus aureus associated with increased mortality in diabetic patients; Mantey I et al.; Diabetic patients with foot ulceration have a poorer prognosis than those without ulceration . The reason for this is unclear, but there is considerable interest in the putative links between infection and atherogenesis, and it is notable that diabetic foot ulcers (DFU) are often infected with Staphylococcus aureus and the main cause of death in DFU patients is ischaemic heart disease . We examined the 5 year survival of 71 diabetic patients who presented with foot ulcers that were newly infected (Sa group, n = 56) or not infected at all during the study period (non-Sa group, n = 15) with S . aureus . Twenty-nine patients (52%) infected with S . aureus died compared with three patients (20%) whose foot ulcers were not infected with S . aureus . The patients in the two groups were similar in age and duration of diabetes . The overall five year mortality rate was 10.4% per year for those infected, significantly higher than the average of 4.0% for patients without infection (p = 0.015) . None of the patients was bacteraemic or died directly from sepsis . Infection of DFU by S . aureus may increase the risk of death in diabetic patients. Indian J Med Res, 2001 Jan, 113, 11 - 3 Inactivation of chloramphenicol by Staphylococcus aureus biotype C from humans & animals; Dutta GN et al.; During an investigation, 55 biotype C (bovine and caprine biotype) Staphylococcus aureus isolated from 43 cows suffering from mastitis, and 20 biotype C Staph . aureus strains from the nares and the side of nail-tips of the right thumbs of 20 farm workers (milkers and animal attendants) on six small dairy farms in Assam and Meghalaya were isolated . Three strains from the former and six strains from the latter from among the isolates on two of the farms were found resistant to chloramphenicol, when tested with a routine susceptibility test . Test of the organisms by the agar dilution method indicated that the resistant strains had a minimal inhibitory concentration for chloramphenicol of 32 micrograms/ml or more, while, the chloramphenicol sensitive strains and two reference strains, Staph . aureus ATCC 25923 and Micrococcus luteus ATCC 9341, had < or = 8 micrograms/ml . Two bovine and five human chloramphenicol resistant strains showed positive results when tested by the Gots test . When these strains were tested by a standard method in broth, containing 30 micrograms chloramphenicol per ml, all showed evidence of inactivating chloramphenicol up to a non-detectable level within 36 h . Inactivation of chloramphenicol by Staph . aureus has clinical significance. J UOEH, 2001 Mar 1, 23(1), 59 - 67 {A case of pemphigus foliaceus associated with bullous impetigo successfully treated with tetracycline and nicotinamide}; Izu K et al.; A 50-year-old Japanese woman visited our clinic, complaining of generalized erythema with painful erosions and bullae . The histopathological findings of the skin lesion suggested development of impetigo . Gentamycin-resistant Staphylococcus aureus was detected by the bacterial culture examination from the impetiginous bullae . A direct immunofluorescence study of the lesion showed an intercellular deposition of IgG and C3 in the upper epidermis . We diagnosed this case as pemphigus foliaceus associated with bullous impetigo . A combined oral administration of tetracycline (200 mg/day) and nicotinamide (1200 mg/day) for 3 weeks was successful . In Japan, patients with moderate to severe symptoms of pemphigus foliaceus are usually treated with oral steroid therapy . To our knowledge, however, there is no reported pemphigus case which has been successfully treated only with tetracycline and nicotinamide. J Biol Chem, 2001 May 4, 276(18), 14955 - 60 Epub 2001 Feb 14. Role of cysteinyl residues in sensing Pb(II), Cd(II), and Zn(II) by the plasmid pI258 CadC repressor; Sun Y et al.; The cadCA operon of Staphylococcus aureus plasmid pI258 confers resistance to salts of the soft metals lead, cadmium, and zinc . The operon is regulated by CadC, a member of the ArsR family of metal-responsive transcriptional repressors . In this study the role of the five cysteine residues of CadC in soft metal ion sensing was investigated . Cys-7, Cys-11, Cys-52, Cys-58, and Cys-60 were changed individually to glycine or serine residues . The effect of the cadC mutations was examined in Escherichia coli using a green fluorescent protein reporter system . None of the mutations affected the ability of CadC to repress gfp expression . Neither Cys-11 nor Cys-52 was required for in vivo response to Pb(II), Zn(II), or Cd(II) . Cys-7, Cys-58, or Cys-60 mutations each reduced or eliminated soft metal sensing . Wild-type and mutant CadC proteins were purified, and the effect of the substitutions on DNA binding was determined using a restriction enzyme protection assay . Binding of wild-type CadC protected cad operator DNA from digestion at the single SspI site, and the addition of Pb(II), Zn(II), or Cd(II) resulted in deprotection . Chemical modification of the cysteine residues in CadC had no effect on protection but eliminated deprotection . C11G and C52G proteins exhibited wild-type properties in vitro . C7G, C58S, and C60G proteins were able to be protected from SspI digestion but had reduced responses to soft metal ions . The results indicate that Cys-7, Cys-58, and Cys-60 are involved in sensing those soft metals and suggest that they are ligands to Pb(II), Zn(II), and Cd(II). J Nat Prod, 2001 Mar, 64(3), 399 - 400 Daucane sesquiterpenes from Ferula hermonis; Galal AM et al.; The roots of Ferula hermonis Boiss yielded two new daucane esters, 14-(4'-hydroxybenzoyloxy)dauc-4,8-diene (1) and 14-(4'-hydroxy-3'-methoxybenzoyloxy)dauc-4,8-diene (2), together with the four known sesquiterpenes jaeschkeanadiol p-hydroxybenzoate (3), jaeschkeanadiol benzoate (4), jaeschkeanadiol (5), and epoxyjaeschkeanadiol (6) . The identities of the isolated compounds were ascertained primarily using NMR and MS data . Compounds 1 and 3 exhibited antimicrobial activity against Staphylococcus aureus with IC(50) 1.5 and 3.5 microg/mL, respectively, and against Methicillin-resistant S . aureus with IC(50) 2.0 and 4.0 microg/mL, respectively. Bioorg Med Chem Lett, 2001 Mar 26, 11(6), 797 - 801 Anti-MRSA cephems . Part 1: C-3 substituted thiopyridinium derivatives; Springer DM et al.; Sixteen novel cephalosporin derivatives with activity against methicillin-resistant Staphylococcus aureus (MRSA) are described . The compounds were synthesized using substituted thiopyridones, generated either by cyclization of functionalized precursors, or by direct alkylation of the enolate of 2-methyl substituted pyrones . The most active compound in vitro against a strain of MRSA (A27223) displayed an MIC of 0.5 microg/mL . The most efficacious compound in vivo had a PD50 of 2.1 mg/kg. J Pept Sci, 2001 Feb, 7(2), 74 - 81 Antibiotic activity of pentadecapeptides modelled from amino acid descriptors; Lejon T et al.; Pentadecapeptides based on modified murine lactoferricin (LFM) sequences show varying degrees of antibacterial activity against Escherichia coli and Staphylococcus aureus . By means of projections to latent structures (PLS), a good correlation is obtained if the biological activity is modelled as a function of variables describing peptide properties, e.g . alpha-helicity, hydrophobicity/hydrophilicity and charge . Using variables derived from a principal component analysis (PCA) of all naturally occurring amino acids, it is possible to describe the amino acid content of the peptides using three variables per amino acid position . The resulting descriptor matrix is then used to develop quantitative structure-activity relationships (QSAR) . It is shown that the theoretically derived descriptors model the activity of the peptides better than the earlier model, and that properties of the peptides other than antibacterial activity can be predicted. J Bacteriol, 2001 Apr, 183(8), 2417 - 24 Recruitment of the mecA gene homologue of Staphylococcus sciuri into a resistance determinant and expression of the resistant phenotype in Staphylococcus aureus; Wu SW et al.; Strains of methicillin-resistant Staphylococcus aureus (MRSA) have become the most important causative agents of hospital-acquired diseases worldwide . The genetic determinant of resistance, mecA, is not a gene native to S . aureus but was acquired from an extraspecies source by an unknown mechanism . We recently identified a close homologue of this gene in isolates of Staphylococcus sciuri, a taxonomically primitive staphylococcal species recovered most frequently from rodents and primitive mammals . In spite of the close sequence similarity between the mecA homologue of S . sciuri and the antibiotic resistance determinant mecA of S . aureus, S . sciuri strains were found to be uniformly susceptible to beta-lactam antibiotics . In an attempt to activate the apparently "silent" mecA gene of S . sciuri, a methicillin-resistant derivative, K1M200 (for which the MIC of methicillin is 200 microg/ml), was obtained through stepwise exposure of the parental strain S . sciuri K1 (methicillin MIC of 4 microg/ml) to increasing concentrations of methicillin . DNA sequencing of the mecA homologue from K1M200 revealed the introduction of a point mutation into the -10 consensus of the promoter: the replacement of a thymine residue at nucleotide 1577 in the susceptible strain K1 by adenine in the resistant strain K1M200, which was accompanied by a drastic increase in transcription rate and the appearance of a new protein that reacted with monoclonal antibody prepared against the penicillin-binding protein 2A (PBP2A), i.e., the gene product of S . aureus mecA . Transduction of mecA from K1M200 (cloned into a plasmid vector) into a methicillin-susceptible S . aureus mutant resulted in a significant increase of methicillin resistance (from a methicillin MIC of 4 micro/ml to 12 and up to 50 microg/ml), the appearance of a low-affinity PBP detectable by the fluorographic assay, and the production of a protein that reacted in a Western blot with monoclonal antibody to PBP2A . Antibiotic resistance and the protein products disappeared upon removal of the plasmid-borne mecA homologue . The observations support the proposition that the mecA homologue ubiquitous in the antibiotic-susceptible animal species S . sciuri may be an evolutionary precursor of the methicillin resistance gene mecA of the pathogenic strains of MRSA. Am J Kidney Dis, 2001 Apr, 37(4), 815