{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T06:42:32Z","timestamp":1774680152267,"version":"3.50.1"},"reference-count":34,"publisher":"Scientific Foundation Spiroski (publications)","issue":"1","license":[{"start":{"date-parts":[[2018,12,22]],"date-time":"2018-12-22T00:00:00Z","timestamp":1545436800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Open Access Maced J Med Sci"],"abstract":"<jats:p>AIM: To determine the distribution of vancomycin MIC and the frequency of S. aureus strains with reduced vancomycin susceptibility among Methicillin-Resistant Staphylococcus aureus (MRSA) isolates.\r\nMETHODS: MRSA isolates (n = 100) were tested for reduced susceptibility to vancomycin using\u00a0 MIC broth microdilution method (BMD), vancomycin screening agar with different vancomycin concentrations with and without casein, and Vitek 2 system.\r\nRESULTS: BMD detected (22%) vancomycin-intermediate S. aureus (VISA) and (78%) vancomycin-susceptible S. aureus (VSSA) but couldn\u00e2\u20ac\u2122t detect nine (Heterogeneous VISA) (hVISA)\u00a0\u00a0 isolates (9%) with MIC \u00e2\u2030\u00a4 2 \u00c2\u00b5g\/ml that grew on screening agar 4 \u00c2\u00b5g\/ml or 6 \u00c2\u00b5g\/ml. Adding casein to vancomycin screening agar increased detection rate of VISA by 4.5%.\u00a0 Screening agar with 6 \u00c2\u00b5g\/ml vancomycin overall detection rate for VISA was 95.45%. Probable \u00e2\u20ac\u02dcpre-hVISA\u00e2\u20ac\u2122isolates (17%) showed growth on vancomycin screening agar 2 \u00c2\u00b5g\/ml with casein. Vitek 2 system failed to detect any VISA isolates.\r\nCONCLUSION: Vancomycin screening agar; 2 \u00c2\u00b5g\/ml and (4 and 6 \u00c2\u00b5g\/ml) were able to detect; probable \u00e2\u20ac\u0153pre hVISA and (hVISA and VISA) isolates respectively based on their BMD MIC values. Decreased vancomycin susceptibility in MRSA isolates might be related to MIC creep. Analysis of vancomycin MIC values over longer periods is recommended to further study this phenomenon and its impact on vancomycin treatment failure.\r\n\u00a0\r\nABSTRACT\r\nAims: Determine the distribution of vancomycin MIC and the frequency of S. aureus strains with reduced vancomycin susceptibility among MRSA isolates.\r\n\u00a0Methods: \u00a0MRSA isolates\u00a0(n =100) were tested for reduced susceptibility to vancomycin using\u00a0 MIC broth microdilution method(BMD), vancomycin screening agar with different vancomycin concentrations with and without casein, and Vitek 2 system.\r\n\u00a0Results: BMD detected (22%) vancomycin intermediate S. aureus(VISA) and (78%) vancomycin susceptible S. aureus(VSSA) but failed to detect nine (Heterogeneous VISA) (hVISA)\u00a0\u00a0isolates (9%) with MIC \u00e2\u2030\u00a42ug\/ml that grew on screening agar 4ug\/ml or 6 ug\/ml. Adding casein to vancomycin screening agar increased detection rate of VISA by 4.5%.\u00a0 Screening agar with 6 ug\/ml vancomycin over all detection rate for VISA was 95.45%. Probable \u00e2\u20ac\u02dcpre-hVISA\u00e2\u20ac\u2122isolates (17%) showed growth on vancomycin screening agar 2\u00c2\u00b5g\/ml with casein. Vitek 2 system failed to detect any VISA isolates.\r\nConclusion: vancomycin screening agar; 2 \u00c2\u00b5g\/ml and (4 and 6 \u00c2\u00b5g\/ml) were able to detect; probable \u00e2\u20ac\u0153pre hVISA and (hVISA and VISA) isolates respectively based on their BMD MIC values. Decreased vancomycin susceptibility in MRSA isolates might be related to MIC creep. Analysis of vancomycin MIC values over longer periods of time is recommended to further study this phenomenon and its impact on vancomycin treatment failure.\r\n\u00a0\r\n\u00a0<\/jats:p>","DOI":"10.3889\/oamjms.2019.009","type":"journal-article","created":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T11:36:17Z","timestamp":1546774577000},"page":"12-18","source":"Crossref","is-referenced-by-count":12,"title":["Vancomycin MIC Distribution among Methicillin-Resistant Staphylococcus Aureus. Is Reduced Vancomycin Susceptibility Related To MIC Creep?"],"prefix":"10.3889","volume":"7","author":[{"given":"Hala B.","family":"Othman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rania M.","family":"Abdel Halim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma Alzahraa M.","family":"Gomaa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malaka Z.","family":"Amer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"52292","published-online":{"date-parts":[[2018,12,22]]},"reference":[{"key":"61013","doi-asserted-by":"crossref","unstructured":"Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. The Journal of antimicrobial chemotherapy. 1997; 40(1):135-6. https:\/\/doi.org\/10.1093\/jac\/40.1.135 PMid:9249217","DOI":"10.1093\/jac\/40.1.135"},{"key":"61014","doi-asserted-by":"crossref","unstructured":"Di Gregorio S, Perazzi B, Ordonez AM, De Gregorio S, Foccoli M, Lasala MB, Garc\u00c3\u00ada S, Vay C, Famiglietti A, Mollerach M. Clinical, microbiological, and genetic characteristics of heteroresistant vancomycin-intermediate Staphylococcus aureus bacteremia in a teaching hospital. Microbial Drug Resistance. 2015; 21(1):25-34. https:\/\/doi.org\/10.1089\/mdr.2014.0190 PMid:25535825 PMCid:PMC4367492","DOI":"10.1089\/mdr.2014.0190"},{"key":"61015","doi-asserted-by":"crossref","unstructured":"Nadarajah R, Post LR, Liu C, Miller SA, Sahm DF, Brooks GF. Detection of vancomycin-intermediate Staphylococcus aureus with the updated Trek-Sensititre System and the MicroScan System: comparison with results from the conventional Etest and CLSI standardized MIC methods. American journal of clinical pathology. 2010; 133(6):844-8. https:\/\/doi.org\/10.1309\/AJCPMV1P0VKUAZRD PMid:20472841","DOI":"10.1309\/AJCPMV1P0VKUAZRD"},{"key":"61016","doi-asserted-by":"crossref","unstructured":"Edwards B, Milne K, Lawes T, Cook I, Robb A, Gould IM. Is vancomycin MIC \"creep\" method dependent? Analysis of methicillin-resistant Staphylococcus aureus susceptibility trends in blood isolates from North East Scotland from 2006 to 2010. Journal of clinical microbiology. 2012; 50(2):318-25. https:\/\/doi.org\/10.1128\/JCM.05520-11 PMid:22135252 PMCid:PMC3264194","DOI":"10.1128\/JCM.05520-11"},{"key":"61017","doi-asserted-by":"crossref","unstructured":"Rojas L, Bunsow E, Munoz P, Cercenado E, Rodr\u00c3\u00adguez-Cr\u00c3\u00a9ixems M, Bouza E. Vancomycin MICs do not predict the outcome of methicillin-resistant Staphylococcus aureus bloodstream infections in correctly treated patients. Journal of antimicrobial chemotherapy. 2012; 67(7):1760-8. https:\/\/doi.org\/10.1093\/jac\/dks128 PMid:22556382","DOI":"10.1093\/jac\/dks128"},{"key":"61018","doi-asserted-by":"crossref","unstructured":"Devi Y, Punithavathy PM, Thomas S, Veeraraghavan B. Challenges in the Laboratory Diagnosis and Clinical Management of Heteroresistant Vancomycin Staphylococcus aureus (hVISA). Clinical Microbiology: Open Access. 2015.","DOI":"10.4172\/2327-5073.1000214"},{"key":"61019","unstructured":"CDC. 2012. https:\/\/www.cdc.gov\/hai\/settings\/lab\/visa_vrsa_lab_detection.html"},{"key":"61020","unstructured":"Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Twenty-eighth informational supplements. M100- S28. Wayne, PA (CLSI), 2018."},{"key":"61021","doi-asserted-by":"crossref","unstructured":"Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clinical microbiology reviews. 2010; 23(1):99-139. https:\/\/doi.org\/10.1128\/CMR.00042-09 PMid:20065327 PMCid:PMC2806658","DOI":"10.1128\/CMR.00042-09"},{"key":"61022","doi-asserted-by":"crossref","unstructured":"Tenover FC, Moellering Jr RC. The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus. Clinical Infectious Diseases. 2007; 44(9):1208-15. https:\/\/doi.org\/10.1086\/513203 PMid:17407040","DOI":"10.1086\/513203"},{"key":"61023","doi-asserted-by":"crossref","unstructured":"Yusof A, Engelhardt A, Karlsson \u00c3\u2026, Bylund L, Vidh P, Mills K, Wootton M, Walsh TR. Evaluation of a new Etest vancomycin-teicoplanin strip for detection of glycopeptide-intermediate Staphylococcus aureus (GISA), in particular, heterogeneous GISA. Journal of clinical microbiology. 2008; 46(9):3042-7. https:\/\/doi.org\/10.1128\/JCM.00265-08 PMid:18596146 PMCid:PMC2546754","DOI":"10.1128\/JCM.00265-08"},{"key":"61024","doi-asserted-by":"crossref","unstructured":"Satola SW, Farley MM, Anderson KF, Patel JB. Comparison of detection methods for heteroresistant vancomycin-intermediate Staphylococcus aureus, with the population analysis profile method as the reference method. Journal of clinical microbiology. 2011; 49(1):177-83. https:\/\/doi.org\/10.1128\/JCM.01128-10 PMid:21048008 PMCid:PMC3020420","DOI":"10.1128\/JCM.01128-10"},{"key":"61025","unstructured":"Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. Twenty-fifth informational supplements. M100- S25. Wayne, PA, 2015."},{"key":"61026","doi-asserted-by":"crossref","unstructured":"Vaudaux P, Huggler E, Bernard L, Ferry T, Renzoni A, Lew DP. Underestimation of vancomycin and teicoplanin MICs by broth microdilution leads to underdetection of glycopeptide-intermediate isolates of Staphylococcus aureus. Antimicrobial agents and chemotherapy. 2010; 54(9):3861-70. https:\/\/doi.org\/10.1128\/AAC.00269-10 PMid:20547791 PMCid:PMC2934981","DOI":"10.1128\/AAC.00269-10"},{"key":"61027","doi-asserted-by":"crossref","unstructured":"Hiramatsu K, Kayayama Y, Matsuo M, Aiba Y, Saito M, Hishinuma T, Iwamoto A. Vancomycin-intermediate resistance in Staphylococcus aureus. Journal of global antimicrobial resistance. 2014; 2(4):213-24. https:\/\/doi.org\/10.1016\/j.jgar.2014.04.006 PMid:27873679","DOI":"10.1016\/j.jgar.2014.04.006"},{"key":"61028","doi-asserted-by":"crossref","unstructured":"Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM, Stellrecht K. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrobial agents and chemotherapy. 2008; 52(9):3315-20. https:\/\/doi.org\/10.1128\/AAC.00113-08 PMid:18591266 PMCid:PMC2533486","DOI":"10.1128\/AAC.00113-08"},{"key":"61029","doi-asserted-by":"crossref","unstructured":"Sakoulas G, Moise-Broder PA, Schentag J, Forrest A, Moellering RC, Eliopoulos GM. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. Journal of clinical microbiology. 2004; 42(6):2398-402. https:\/\/doi.org\/10.1128\/JCM.42.6.2398-2402.2004 PMid:15184410 PMCid:PMC427878","DOI":"10.1128\/JCM.42.6.2398-2402.2004"},{"key":"61030","unstructured":"Willey BM, Kreiswirth N, Gelosia A, Porter C, Alqhahtani M, Mazzulli T, Pong-Porter S, Larocque C, Pike K, Kreiswirth NNB, Wong K, Poutanen S, Low DE. Screening for vancomycin-intermediate Staphylococcus aureus (VISA): does casein make a difference?, abstr. D-2210. Abstr. 48th Annu Intersci Conf Antimicrob Agents Chemother. (ICAAC) Infect Dis Soc Am. (IDSA) 46th Annu Meet American Society for Microbiology and Infectious Diseases Society of America, Washington, DC, 2008."},{"key":"61031","unstructured":"Howden BP, Ward PB, Xie S, Wang JL, Johnson PD, Charles PG, Grayson ML. A new agar dilution screening method for the accurate detection of heterogenous-vancomycin intermediate Staphylococcus aureus (hVISA). ASA Newsl. 2004; 19:9-10."},{"key":"61032","doi-asserted-by":"crossref","unstructured":"Riederer K, Shemes S, Chase P, Musta A, Mar A, Khatib R. Detection of vancomycin-intermediately susceptible and heterogeneous Staphylococcus aureus isolates: comparison of Etest and agar screening methods. Journal of clinical microbiology. 2011. https:\/\/doi.org\/10.1128\/JCM.01435-10 PMid:21490190 PMCid:PMC3122762","DOI":"10.1128\/JCM.01435-10"},{"key":"61033","doi-asserted-by":"crossref","unstructured":"Burnham CA, Weber CJ, Dunne WM. Novel screening agar for detection of vancomycin-nonsusceptible Staphylococcus aureus. Journal of clinical microbiology. 2010; 48(3):949-51. https:\/\/doi.org\/10.1128\/JCM.02295-09 PMid:20089765 PMCid:PMC2832426","DOI":"10.1128\/JCM.02295-09"},{"key":"61034","unstructured":"CDC (2015): Investigation and Control of Vancomycin- Resistant Staphylococcus aureus (VRSA), 2015. Update. https:\/\/www.cdc.gov\/hai\/pdfs\/vrsa-investigation-guide-05_12_2015.pdf"},{"key":"61035","doi-asserted-by":"crossref","unstructured":"Walsh TR, Bolmstr\u00c3\u00b6m A, Qw\u00c3\u00a4rnstr\u00c3\u00b6m A, Ho P, Wootton M, Howe RA, MacGowan AP, Diekema D. Evaluation of current methods for detection of staphylococci with reduced susceptibility to glycopeptides. Journal of clinical microbiology. 2001; 39(7):2439-44. https:\/\/doi.org\/10.1128\/JCM.39.7.2439-2444.2001 PMid:11427551 PMCid:PMC88167","DOI":"10.1128\/JCM.39.7.2439-2444.2001"},{"key":"61036","doi-asserted-by":"crossref","unstructured":"Swenson JM, Anderson KF, Lonsway DR, Thompson A, McAllister SK, Limbago BM, Carey RB, Tenover FC, Patel JB. Accuracy of commercial and reference susceptibility testing methods for detecting vancomycin-intermediate Staphylococcus aureus. Journal of clinical microbiology. 2009; 47(7):2013-7. https:\/\/doi.org\/10.1128\/JCM.00221-09 PMid:19420170 PMCid:PMC2708520","DOI":"10.1128\/JCM.00221-09"},{"key":"61037","doi-asserted-by":"crossref","unstructured":"Mason EO, Lamberth LB, Hammerman WA, Hulten KG, Versalovic J, Kaplan SL. Vancomycin MICs for Staphylococcus aureus vary by detection method and have subtly increased in a pediatric population since 2005. Journal of Clinical Microbiology. 2009; 47(6):1628-30. https:\/\/doi.org\/10.1128\/JCM.00407-09 PMid:19403769 PMCid:PMC2691127","DOI":"10.1128\/JCM.00407-09"},{"key":"61038","doi-asserted-by":"crossref","unstructured":"Kruzel MC, Lewis CT, Welsh KJ, Lewis EM, Dundas NE, Mohr JF, Armitige LY, Wanger A. Determination of vancomycin and daptomycin MICs by different testing methods for methicillin-resistant Staphylococcus aureus. Journal of clinical microbiology. 2011; 49(6):2272-3. https:\/\/doi.org\/10.1128\/JCM.02215-10 PMid:21450951 PMCid:PMC3122735","DOI":"10.1128\/JCM.02215-10"},{"key":"61039","doi-asserted-by":"crossref","unstructured":"Cook AM, Ramsey CN, Martin CA, Pittman T. Linezolid for the treatment of a heteroresistant Staphylococcus aureus shunt infection. Pediatric neurosurgery. 2005; 41(2):102-4. https:\/\/doi.org\/10.1159\/000085165 PMid:15942282","DOI":"10.1159\/000085165"},{"key":"61040","doi-asserted-by":"crossref","unstructured":"Yanagihara K, Okada M, Fukuda Y, Imamura Y, Kaneko Y, Ohno H, Higashiyama Y, Miyazaki Y, Tsukamoto K, Hirakata Y, Tomono K. Efficacy of quinupristin-dalfopristin against methicillin-resistant Staphylococcus aureus and vancomycin-insensitive S. aureus in a model of hematogenous pulmonary infection. Chemotherapy. 2004; 50(5):260-4. https:\/\/doi.org\/10.1159\/000081948 PMid:15528893","DOI":"10.1159\/000081948"},{"key":"61041","doi-asserted-by":"crossref","unstructured":"Schmitz FJ, Krey A, Geisel R, Verhoef J, Heinz HP, Fluit AC, SENTRY Participants Group. Susceptibility of 302 methicillin-resistant Staphylococcus aureus isolates from 20 European university hospitals to vancomycin and alternative antistaphylococcal compounds. European Journal of Clinical Microbiology and Infectious Diseases. 1999; 18(7):528-30. https:\/\/doi.org\/10.1007\/s100960050340 PMid:10482037","DOI":"10.1007\/s100960050340"},{"key":"61042","doi-asserted-by":"crossref","unstructured":"Aucken HM, Warner M, Ganner M, Johnson AP, Richardson JF, Cookson BD, Livermore DM. Twenty months of screening for glycopeptide-intermediate Staphylococcus aureus. Journal of Antimicrobial Chemotherapy. 2000; 46(4):639-40. https:\/\/doi.org\/10.1093\/jac\/46.4.639-a PMid:11020266","DOI":"10.1093\/jac\/46.4.639-a"},{"key":"61043","doi-asserted-by":"crossref","unstructured":"Wootton M, Howe RA, Hillman R, Walsh TR, Bennett PM, MacGowan AP. A modified population analysis profile (PAP) method to detect hetero-resistance to vancomycin in Staphylococcus aureus in a UK hospital. Journal of Antimicrobial Chemotherapy. 2001; 47(4):399-403. https:\/\/doi.org\/10.1093\/jac\/47.4.399 PMid:11266410","DOI":"10.1093\/jac\/47.4.399"},{"key":"61044","doi-asserted-by":"crossref","unstructured":"Denis O, Nonhoff C, Byl B, Knoop C, Bobin-Dubreux S, Struelens MJ. Emergence of vancomycin-intermediate Staphylococcus aureus in a Belgian hospital: microbiological and clinical features. Journal of antimicrobial chemotherapy. 2002; 50(3):383-91. https:\/\/doi.org\/10.1093\/jac\/dkf142 PMid:12205063","DOI":"10.1093\/jac\/dkf142"},{"key":"61045","doi-asserted-by":"crossref","unstructured":"Pierard D, Vandenbussche H, Verschraegen I, Lauwers S. Screening for Staphylococcus aureus with a reduced susceptibility to vancomycin in: a Belgian hospital. Pathologie Biologie. 2004; 52(8):486-8. https:\/\/doi.org\/10.1016\/j.patbio.2004.07.016 PMid:15465269","DOI":"10.1016\/j.patbio.2004.07.016"},{"key":"61046","doi-asserted-by":"crossref","unstructured":"Chen CJ, Huang YC. New epidemiology of S taphylococcus aureus infection in A sia. Clinical Microbiology and Infection. 2014; 20(7):605-23. https:\/\/doi.org\/10.1111\/1469-0691.12705 PMid:24888414","DOI":"10.1111\/1469-0691.12705"}],"container-title":["Open Access Macedonian Journal of Medical Sciences"],"original-title":[],"link":[{"URL":"https:\/\/oamjms.eu\/index.php\/mjms\/article\/download\/oamjms.2019.009\/2732","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/oamjms.eu\/index.php\/mjms\/article\/download\/oamjms.2019.009\/2768","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T08:33:03Z","timestamp":1692520383000},"score":1,"resource":{"primary":{"URL":"https:\/\/oamjms.eu\/index.php\/mjms\/article\/view\/oamjms.2019.009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,22]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1,15]]}},"URL":"https:\/\/doi.org\/10.3889\/oamjms.2019.009","relation":{},"ISSN":["1857-9655"],"issn-type":[{"value":"1857-9655","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,22]]}}}