Scribd Logo
Upload

Welcome to Scribd!

  • A Review On Mechanism of Action, Resistance, Synergism, and Clinical Implications of Mupirocin Against Staphylococcus Aureus - Elsevier Enhanced Reader

    Uploaded by

    John
    40 views11 pages
    Mupirocin, Staphylcoccus aureus, Antibiotic Resistance

    Original Title

    A review on mechanism of action, resistance, synergism, and clinical implications of mupirocin against Staphylococcus aureus | Elsevier Enhanced Reader

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Report this Document
    Mupirocin, Staphylcoccus aureus, Antibiotic Resistance

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    40 views11 pages

    A Review On Mechanism of Action, Resistance, Synergism, and Clinical Implications of Mupirocin Against Staphylococcus Aureus - Elsevier Enhanced Reader

    Uploaded by

    John
    Mupirocin, Staphylcoccus aureus, Antibiotic Resistance

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 11
    ‘Biomedicine & Pharmacotherapy 109 (2019) 1809-1818 Contents lists available at ScienceDirect Biomedicine & Pharmacotherapy ELSEVIER journal homepage: www.elsevier.com/locate/biopha A review on mechanism of action, resistance, synergism, and clinical implications of mupirocin against Staphylococcus aureus me ‘Saeed Khoshnood””, Mohsen Heidary*", Arezoo Asadi‘, Saleh Soleimani', ‘Moloudsadat Motahar*”, Mohammad Savari*, Morteza Saki", Mahtab Abdi‘ Degree, Pcl of Men A Sunshar Unversty of Meal Sees, Ao, ran * sd asereh Gane, Aa shaper Ono of Medel Sees, Aa rn “Deparment of Marty, Sea of Meng ran tony of eS, Tera at “Dapemen of say, Peyme Nese Unvey,iftan, kan alr od Molec sae Cnr, Aer osha Une of Medal Sean, Aes, rat P ARTICLE INFO ApSTRACT Keywris: ‘Muplrocln (UP), bactroban, or peeudomonle acid i naturel crotnie acd derivative drug extracted from Sep aes ‘Psoudoronas fuorescns which s produced by snodularpoyketde synthases. upton ‘This ancbotc has @ unique chemical structure and mechanism of ston. Itisamisture of A-D pseudomenie — ‘acids and inhibits protein syuthess through binding to bacterial solcucy 1024 ig/ml, and 2.4% (= 10) isolates had MIC values of 1-82 ug/ml [36]. Inthe study performed by Ramsey etal, in the United States, the characterises of MUP-resstan S. aureus isolates (18, aureus stains with high-level resistance and 19 8. aureus strains with low-level Blonetene 8 aracohrey 19 2019) 180-1818 [lketonatase [Tioesense [Aqitansense []Oehydame [Acari poten [ketodictse [Methytvansfease 0G Mug Mun) Mk Nin Ni dep Ng? mp _ ttle Modules Module 2; ou =o on 0H ni on ee a a aP B= =0\=0 Ho a on Se Moni ce ig. 4 The muplrocin biosynthesis genes and the proposed pathway of muplrcin production. (The figure wes adopted and reproduced fom Thomas et al. with ermision for the publisher) [9] resistance) were defined. The results demonstrated that in some of the isolates low-level MUP resistance was related to mupA gene. In adi tion, both mechanisms of MUP resistance were shown from several ‘various clones in different geographic regions US [37] Antonov et al. performed a study on 358. aureus strains isolated from 249 outpatient children i New York City. They demonstrated that in the beginning of the study, approximately 19% (n = 68) of children were infected with MUP-resistant Saurus. AS wel a, approximately 31% (a = 110) of S. aureus strains isolated during the period of in- vestigation were MUP-esstant, mostly due to widespread MUP uses Gay 42.2. Asia In Asia, both low-level and high-level MUP resistance were reported ‘among Stapylocccus isolates. However, the rate of resistance is dif= ferent in various geographic areas (Fable 1) In South Korea, MUP utilization has began since 1994 and the rst ‘case of resistance was reported in 2003, Yoo etal. in their study de- tected 6.1496 (n = 25) high-level and 2.89% (n = 21) low-level MUP- resistant §, aureus folates, of which 21 high-level MUP-resistantis0- lates had the most predominant mupA restriction fragment length polymorphism type [35] In another study, Youn et al. performed # 10-year (2003-2013) follow-up study on MUP prescription in a Korean hospital. They de- ‘monstrated that during these 10 years (from the beginning of the study to the end of i, the annual MUP utilization almost doubled. In this period, the prevalence of high-level and low-level MUP-resistant MRSA Isolates doubled and tripled, respectively [40]. Pujimura etal. carried out a study on 1368 MRSA strains isolated from 15 general Japanese hospitals during 1997-2001 to determine the prevalence of MUP resistance, Although the rate of low-level MUP. resistant MRSA strains was increased from 0.8% (n = 2261) in 1997 t0 2.4% (n = 6254) in 2001, high-level MUP-resistant MRSA strains were ‘ot isolated [41]. Rodresh etal. conducted an investigation in India on 98 S. aureus strain isolated from skin and soft-tissue to document the rate of MUP resistance. The prevalence of high-level MUP resistant S. aureus strains was 8.29% (n= 8) and the prevalence of low-level MUP-resistant S. aureus strains was 17% (n= 17) 42]. Lu et al. reported the rate of MRSA isolates with high-level MUP resistance in China, From the 803 MRSA isolates studied, 6.6% (n = 53) were highevel MUP-esistant isolates, while the low-level MUP-e sistant MRSA isolates were not detected [4] 3.2.3. Burope In european counties, different reports about the status of current patterns of MUP resistance in S. aureus were enclosed (Table 1). In Europe, high-level MUP resistance among $. aureus isolates was frst reported in the UK in 1961, Nowadays, the data shows that low-level [MUP-resitant MRSA isolates were increased [4]. ‘Schmitz et al. have Investigated the prevalence of low-level and high-level MUP resistance among 699 S. aureus strain isolated from 19 European hospitals. MUP susceptibility tests demonstrated that high level and low-level MUP resistance were detected among 1.6% (n= 11) and 2:39 (n = 2.3) ofS. qureus isolates, respectively [45}. Inthe study performed by Le tal ina Swiss tertiary care hospital, the trends in MUP-resisant MRSA isolates were shown. They demon: strated that low-level MUP resistance surprisingly increased among clinical isolates of MRSA during 1999-2008 years [from 0% (n = 17) t0 7996 (n= 19)1 [461 In another study carried out by Moothouse et alin Ireland, the MUP susceptibility tests were done for 152°. aureus isolates. Overall ofthis Road ea Blonetene 8 aracohrey 19 2019) 180-1818 ‘Table 1 Prevalence of mupirocin resistance worwide weston ence Publton date Baia Ne, mc a esace sfreisast (ayn) mecha = feces ‘ated 1982 Sara 30 ee eso igo 2) sap i) masmaD aed 1993 Sau ‘0 eae | . go 5) 409 2520) an) 1969 Sora a) S218) mip gene asa) Spiel hoon Sms 46. 102400 imwa0 ates 251 201 masa 409 eaea.- osha 10 psiz woo South vores) 2803 Sain See mp gene Same ‘ane dase 12 gene oma. 5% 00) ext: ens 21,3400) a3 a3, 167% a9 saa 7 205 Scum 20) 200 . a roa seo) South Aton (8612006, msn . 200 . e spate 31 205 asa « - esa gene nas Ganda 53 207 asa 3360) - mga pene a wee) eo) usa 8 207 mass nw eau - tow 250) psi200 Bence sip 9) 20 uns Sw we sia) 20 351200 Benan sea (11 208 5 Poona sab 7 : aD 10) Oo Toke) 28 sansa ” 5 12 gene on tld) 209 ssa cons: sam - bars asa row panes) bea), 2600 Seam 20) ssa: Slo a). 1% 00 ens ow, 226 00 Nigeria 209 Saas aw eam | wreway se pices 0 22600 8A 81 2109 asa a Basa = Doma 3a 351200 oman aa (96) amo ssa 5 6H) 1a ena) ano as 09 os oman alien (71 am as 2a) $200 * oan ssaganore (95 an ‘cans sk 8.2560) se pve . ssa basa asia o@.109 eons: 21,7700) usa oo am asa a : mg ge ro 8 C00) am asa rs : mga foe DaRs ssa San 00 279, 101% 0) 109,500 35%), 179% 60 tn 1001 aa versa - 200 - ss South ores 02) 2012 asa sow eaea nema 10) S60 samt) enti) ama msn ou . . ery ssa 2a) ronan maa 904 ams Saw 20 200 5 Son con 300 sean 1051 ams masa 7 5 . ne msn France (381 ams asa sins . mga pve ans can 30,200 1), 008 00 5510, 4000) S70, 56% 00 ‘naa (10) 2m suas 7a exeay = term 5a) 351200 sss aa ama Sau 20 easea- 5 aves cans 151) psi209 rsa), 82600 Bom cy, 15.6% 0 (continued om next pe) Road ea Blonetene 8 aracohrey 19 2019) 180-1818 ‘Table 1 (conned) weston cence Pbleton date Baca No, mc ‘esac estan reust ayn) te sa L071 aoe Sara 7 ro ga poe oan Bulga 105) aus nasa ns: pas DRS: ssa 250,900 >2560 2, 319600 1@.400 Da, 06% a0 sna (01 ams as 10 eaeay = Bea) 300 psi200 rma tn (110) aus sansa. 7 5 mg poe 138) ssa usa cn) ams Sime ssw eam = 3% 6) pices a9 ss7won ina (12) aus S tte 30 2m Main VS88F 22) roa SUReaD wine 7390) ks seme) ES gene 9 appt 0s) ane S.aweas sa 2500) mip pee sas) 50D >s1200 simap maa 0141 ame cans +o 520 mg gre ass zap zeman ra 1151 ans as ap porap aascn fr (18 an8 Sai 2 : : an as vasa s : up gene tom, a7 mass coc 35120) ma pene sas a0 7 ans sou) nove > swap Abbreviations | Law levelestant | Intermediate levelesstant H High lve resistant; CONS coagulasenegtivestaphylococel) MRSA mthiilin resistant sa: Phylocoeas cues. isolates, 2% (x = 28) were MUP-resstant [47]. high-level resistance and 1.4% (n = 5) low-level resistance and Desroches etal. conducted a study on epidemiology of the MUP. survey the mpB gene was not detected (48). resistant MRSA isolates in France and detected a MUP-resistant MRSA, clone earring mupA gene. They showed that of 367 MRSA clinical so 3.2.4. afica lates, 2.296(n = 8) were resistant to MUP, of which 0.8% (n= 3) had” few studies have been done to report the prevalence of high evel ‘ied Fass = << CED MRSA (1) 3% -MSSA: 0% (L), 19% (H)| 1 46%), 8650) 2) 29%), 03% 0) 3) 68% 1%, 5609 4) 99% 239% saene aera 4 © Sf.5)25% 0), 75% 00, ‘and low-level MUP-resistant S, aureus (solates fn Africa and cureent MUP resistance patterns is uneleat in sub Saharan Aftiea (Table 1). In the study performed by Fritz et al, 1089 patients infected with skin and soft tissue infections were followed for up to one year to identify MUP-reistant S aureus isolates, They reported that 21% (= 23) of patients were infected with S. aureus isolates which were high-level resistant to MUP (49). [ieholson and colleagues have reported the prevalence of low-level and high-level resistance to MUP among MRSA isolates. They showed ‘that 30% of MRSA isolates were low-level and 24% high-level resistant to MUP [50]. ‘Moyo etal have conducted a study on 89 patients infected with S ‘aureus isolates. They reported that 25% (n = 22) ofthe isolates were MRSA, of which 1.1% (n= 1) were MUP-esistant [51]. Inanother study done by Orret, 188 MRSA isolates mostly collected from bloodstream and surgical ste infections were tested for MUP re- sistance. He showed that 2696 (n = 49) of MRSA isolates were high: level and 4496 (n = 83) low-level resistant to MUP (52. ‘Monecke et al. have conducted a study on 294 S. aureus strains isolated during 2012-2013 years. They reported that 15.3% (n = 45) of ‘these strains were MRSA, of which 5.8% (n = 17) were mupA-posiive isolates (53) 4. Synergism Synergy Is the cooperation of two or more agents to produce a ‘combined effect greater than the sum of thelr separate effets and drug, ‘synergism isan interaction between two or more drugs that eauses the total effect of the drugs to be greater than the sum of the individval effects ofeach drug. A synergistic effect can be beneficial or harmful ‘The studies on synergism against staphylococcus species are very limited and few researchs have been reported. In current study, the synergism of MUP with amoxicilin-lavulanate, monoterpenes, HT61, ‘and propolis against MRSA was reported. 4.1. Symergiom of mupirocin with amosiilin-lavanate against MRSA In order to fight against MRSA isolates, combinations of MUP and ‘amoxicilin-clavulanate have been studied and confirmed that this sy- ‘nergy had a therapeutic benefit in the prevention of staphylococcal in fection (54,551. ‘Alou et a, have demonstrated that combinations of MUP as an in hibitor of protein synthesis and amoxicillin elavulanate as an inhibitor ‘of cell wall synthesis can show synergistic activity against MRSA and. MSSA isolates in vitro. They have reported synergy for 1546 (n= 2) of [MSSA isolates and 2096 (n = 2) of MRSA isolates [54 In another study performed by Ghiselli eta, it was used arat model to study the effect of MUP inthe prophylaxis against. aureus vascular ‘graft infection. They shown that the MUP-amoxicilin-levulanate ‘combination can completely inhibit the MSSA and MRSA growth in vivo, (55) 4.2. Synergism of Mupirocin with monoterpenes aganst MRSA ‘The monoterpenes are essential ols which have antibacterial properties specially against S. aureus isolates due to their derivatives (terpencids) (56, 57). For example, Trombetta et al in their study showed the anti- bacterial effect of three types of monoterpenes inching linalyl acetate, menthol and thymol agaist S. aureus strains (56) ‘As well as Hosseinkhani and collegues have demonstrated thatthe monoterpenes including thymol, paracymene, and gamma-terpinene ‘an Inhibit the growth of $. aureus isolates with an inhibitory zone ‘lameter between 30-60 mm and MIC < 0,02 )l/m [57) Kifer etal, performed a study to show the antibacterial effect of three monoterpenes including thymol, menthol and 1,8.cineole Blonetene 8 aracohrey 19 2019) 180-1818 combined with MUP against MRSA isolates in their planktonic and biofilm phases. The results showed thatthe MIGs of MUP were 3fold lower than the MICs of monoterpenes. though the single substance of MUP was failed to eliminate the biofilm, MUP combined with 1,8 c- ncole destroy the MRSA isolates grown in biofilm. MUP combined with ‘menthol showed antagonism effect and MUP combined with thymol had inconclusive effect (53. 4.3, Synergism of Mapirocin with HT61 against MRSA HT6I Isa quinoline-derived cationic bactericidal agen against both MRSA and MSSA isolates which has a synergism effcacy with MUP against S. aureus isolates [59] In the study conducted by Hubbard etal, the mechanism of action of HT61 on bacterial membranes was studied, Thelr study demon: strated that, HT61 can depolarize the membrane to release the inter cellular constituents at concentrations above and below the drug's MIC {co} In another study performed by Hu etal. [61]. the effect of combi nation of HT61 and MUP against of MSSA and MRSA clinical isolates was investigated. In their study, no interaction was reported between HT61 and MUP using the fractional inhibitory concentration index. They reported that HT6I-MUP combination showed a poteney with significant killing of MSSA and MRSA isolates in vivo (mouse mode) 4.4, Synergism of Mupirocin with Propolis against MRSA ‘The studies on natural herbal products have become more valuable than synthetic products, due tothe ineeasing prevalence of bacterial resistance to chemical drugs and also lower cytotoxicity of the herbals {62,63}. Although many studies performed on the effects of natural herbal products in the world, nowadays there are few available herbal medicines for trestment of bacterial infections compared with ant biaties (64,65). Propolis, a natural resinous substance collected by honeybees from several plants, Is @ complex mixture of compounds such as botanical Dalsams and resin with Dees’s digestive enzymes. Propolis has ant bacterial properties including both bacteriostatic and bactericidal ac- Lives whieh is mostly because ofthe phenolic acid fraction [8,66] Ina study performed by Darwish and colleagues, they reported antibacterial effect of propolis against MRSA isolates. The resuls of, broth mierodilution method demonstrated that propolis type I with MIC 4,69 ig/ml and type Il with MIC 18.75 ug/ml had antibacterial activity against MRSA Isolates. As well 26, The antimlerobial susceptibility testing showed that the propolis type I produced the highest ant bacterial activity with inhibition zone of 17.00mm than other fractions against the MRSA isolates [67] ‘Onlen et al. in their study evaluated the antibacterial activity of propolis and its synergism with MUP against MRSA isolates in nasal ‘atrage. They have investigated the treatment and control groups in vivo (rabbit model. The treatment groups treated with MUP and the control groups were received phosphate-bufered solution without MUP. The propolis combined with MUP resulted in a signifiant de- ‘crease inthe count of neutrophils in the mucous membranes of rabbits compared with the control group. In this study, the propolis-MUP combination showed significant decrease in bacterial cell count and inflammatory response [08] inical treatment Se Use for nasal decolonisation Due to the lack of FDA breakpoints for MUP, along with limited availability of commercial tests, there Is not specific recommendation ‘on MUP suscepibility testing and specific program for screening the MRSA isolates them from the nose [59]. (ral MUP is not routinely suggested for decolonization and it should ‘only be considered in patients who continue to have infection (69) ‘When the MRSA isolates are epidemic, MUP may be used as a choice rug for nasal decolonisation (70]. In these patients, MUP can be used, to reduce infection despite increasing the MUP resistance [71]. Ina study performed by Dupeyron etal, they have used MUP inthe prevention of MRSA infections for 2242’ patients hospitalized in a ‘gastroenterology unit during a period of 52 months. Overall it was shown that after MUP using, this drug significantly reduced nasal MRSA, colonization (721. Ina prospective cohort study done by Doebbeling etal, the eect of Intranasal MUP ointment agains S. aureus carriage in healthy hospital staff was investigated. The results ofthis study shoved that six months after treatment, the nasal colonization was 489 versus 72% in placebo ‘group; while one year after treatment, the nasal colonization was 53% versus 76% in placebo group [73] -MUP-based nasal decolonization in hemodialysis patients can re- ‘duce the prevalence ofS. aureus bacteremia, Although due tothe threat ‘of MUP resistance it soften not routinely used in this population [74]. ‘Boelart eta. in their study demonstrated that nasal calcium MUP ‘decreased the rate of . cursus bacteremia among patients hospitalized {in the hemodialysis unit. MUP-based nasal decolonization led to era ‘ication of 96% nasal colonization ofS. aureus and decrease from 0.097 {to 0.024 in the incidence of S. aureus bacteraemia (per patient-yeat) 51, ‘5.2. Use for controling outbreaks ‘The infection control programmes can limit the endemic infection o colonization wit drug resistant bacteria such as MRSA isolates [76]. ‘ina randomized controlled research trial Elis and colleagues tar- {gted intranasal MUP for preventing the colonization and infection by ‘isolates of CA-MRSA among soldiers (a highly endemic population). The rilitary trainees natlly colonized with MRSA isolates were treated ‘with intranasal MUP and after a 16 weeks followeing up no MUP re: sistance was detecteds (771 Irish etal carried outa study on an outbreak of an epidemic HA- MRSA and according to UK guidelines used nasal MUP for eradication ‘of the MRSA isolates. During this work a MUP-resistant MRSA emerged in 12 patients and 11 staff. This outbreak control had significant ‘medical, socal and financial implications (78). ‘5.3. Use to prevent recurring infection Approximately 70% of patients infected with CA-MIRSA skin and soft tissue infections will experience recurent infections over one year, ‘even after the best intial therapy. MUP-based decolonization of S. ‘aureus isolates is one ofthe main approaches fr patients colonized with subsequent skin and soft tissue infections (79). ‘Mascit! etal. have done an investigation on prefered treatment and prevention strategies for recurrent CA-MRSA skin and soft-tissue Infections. In this study, approximately 40% (n= 77) of volunteers used MUP with antiseptic body wash. MUP-based decolonization was effective in more than half ofthe patients at preventing subsequent CA- MRSA skin and soft tisue infections [80] In a placebo-controlled study performed by Raz et al, MUP was ‘used to prevent the recurrent staphylococcal nasal colonization and skin infection in 17 patients and was not used in the placebo group (17 [MUP-untreated patients). The results of this study showed that the ‘number of skin infections was 26 in MUP-tested patients and 62 in MUP-untrested patients. As well as, the number of nasal colonization ‘was 22 in MUP-reated patients and 8 MUP-untreated patients [81]. 6. Conclusion [MUP is predominantly used for nasal decolonization and it ean be Blonetene 8 aracohrey 19 2019) 180-1818 considered as a topial drug useful against superficial skin infections such as impetigo or folliculitis eaused by S. aureus isolates. The patients {infected with MRSA isolates has increased the morbidity and merality rates in recent years. An effective global MRSA contol will require the use of combined drugs which the total effects of them are greater than the sum of their separate effects. MUP combined with amoxicilin-le vulanate, monoterpenes, HT, or propolis has a promising synergistic effect against MRSA isolates and decreases the duration of MUP treat ment. This drug also used for prevention of recurring infections and control the outbreaks. MUP also used for prevention of recurring in- feetions and control the outbreaks. However, the data shows that the emergence of MUP resistance following its widespread use i increasing among MRSA isolates worldwide. References 1 Suharto nant race by poms ‘Sc Peeing fie hres Coons o ina Ages ‘id chenaney 097. ‘Osha RB niin? ats Ssone, A Wi Asc ‘city of map endomal aihtaceeeo ar tpt ‘emo Ages Chmote 37) C8) 5-98 Arce yan Arte, A Mone, Gram-negative nd fing cts boring upc bed medcinsaian Sep tut rsozaton a Son, Open Forum neta Dace Oxo ‘nies Pre, 208 bea, eo, BN. ov HF Chamber, Comm scat me ‘cin recon Soptynner mre Let 375 (75) G1 T9915 bn 8 bs Mam etnrobilpper ming ere eg neo nde nanan Go. Toe Chan 6) Ea Pn, The nll ewdopnes mpc, 3 An, cd Demat 28) Ghote San ttt, ade AG Mart, 2 Seng ER Stes a Son apn by aaomons ores NEN 1585 nes Forsbal Pairye 3h Chom a Ee) 0). ‘senna Mpa Pope one ens ho mra ary and estes fey honey ee og) G0) 951 Be ts neal CW Sep Reason yas Sih nto map St Wil 8 @) O10 3 Santa aot see NS D2 dn Can, 2. Gm C2 Rt, Ph, Maat rita {juin yeeros Chom DD) Erik DG Aland LL A Sto, DE Low, J Lng, et Map, 2 Se higher mpc esnce macnn np stn, ‘irk howt Chote 01) AAC 05351 1'SinsindK Gabe ise, b Soe J Clo, dono a, te anton pce y pron fre, Pred fe Th Inanelns Coton en Amici ges aa heathy G78). Shc fanabere Wi Tiel Md 0A Ar Wa Abr eta ‘trons roca: pple Sn erp eee Won 3 ‘emonsyng end Nene 4) 010 S920. SERCH A Bie AR ur P. Worm, LW an via of ‘enn on cial nine Sopher usd fe pe atone nature aygucpe 118) C008 a A Baap etre Pomel Nagy, Ses a oti repr of prin ny fron ae cer al ‘etn cons iting 39 OS GO) 91-0 ‘efi ration rcdononar egies Cooney 311) GW) Sora $e iy op Ages inthe tment of aca ain nn ‘iro Sn Sy sa ante Sy 010 ‘evar eet ng Ent Aoi Reine oto 6) Guna Signe Rie, 9. Gam Kaa, X De Bee, ay oa Jaton aioe pea ot gn ups ce of Wisk les sunt anon Anamico: Chater 70 G2 O15) 5 fg ake, LE Ben MP Fae, Map ence edt inci gto cil elt of ethiornat Spheres pda pple, i Mei 87 2010) 12 Upon lag toma, Mai an upon sce en Pann stents te Ath: Smee Saar Sharan, Lag. Hern R. Acne, Die andi, poo snr, dosh nd lo ene eyo a ol @ I 1 a 1 1 woo} i at ust ua tis} et ba tos) us) 0) en a we Road ea ‘mu or erasing cage of mein eit Staphyocoecs ares, ‘oti: ets Cheat 9 (6) (1999) 1492-1416 {24S Dee, C3 Wary, Tos Abul, BS. Comper. Edgeworth, B Cooks, ‘a, input of muptoel estance on the wansision ad con el ‘easocnnd MRSA, J Anime, Cheater, 70 (12) (2018) 396-3578 125) BD. Cookson, The energnce of mpc estan challenge oneton ‘ia nd antbioepesing pt, Aine. Chote. 41.0) 055) Trae 218 Patel RS. Gow, J. Jernigan, Maponics. 4 (6) cos Sas 90 Si Pate Garis, JA Jenin, Mapa rata, Ci. Infact Di 42 (© ca 935-98. ‘Poole, Gethin H.Humprey Mopiocn reine: iin pcos an potas he radeon of MAS, J Annie Ere 70 (0) (305) 268-2053. {1G Mad, A. Oeil lngham, Fabric Chopra, Ais of mpicia ‘stance and fine Spacer sre by mols gee and Fe ‘eet modeling tecigos, Aotimiah Agents Chenoa (1) (00) Seah D6 Aland, L Laue A Sino, DU Low, J Longin ay Map =| Sew highevel mpc sesaue machen in Saphoccoa een ‘etn Agents Cheater (4) (2012) 1916-1920, Din Gewel, MLV. Franca, Cojugaes in apne bac, asa al fo. be rb (200) 277-258. ‘Wz, XC Patel pA ie ple i aecemary fr ncn an [uni antr tom notes deo Spicer acu in tm etn ets Chen (2012) AAC 0188712. Peer Roth Ldper Agile, J oa ves, Moder Avr igh eve ‘pin ene wn mein estan Saphylococe ur panden expe sib. Chmete 0) (08) 950-30 Fert, Podge, Ree, ECalla, P Courage en ‘odulatons of elt estan ene expres, Cn Moi. Rv. 20 (2) (Gorn mi ‘AE Sina, star ole, Wat Ofer D eve ay loc estan, meen estat Sayers sues sa it {aman orp Ansmica, Ages Chante 51) (2007) 3600-2886. Pekin J Hoge, Falco rh, HB, Vicon Mapa resance ‘erenng of meta vertantSpncors ares aes Madigan Ary Media Gin AGL M173 (6) 08) O40. Md Ramey, 3. Brey, CA. Kana, TM, Noro, J Patera, DBR Regen, Chracermaton of mapcocin ean Supls oe

    You might also like