Reduced vancomycin susceptibility in Staphylococcus aureus clinical isolates: a spectrum of less investigated uncertainties.


Journal

BMC infectious diseases
ISSN: 1471-2334
Titre abrégé: BMC Infect Dis
Pays: England
ID NLM: 100968551

Informations de publication

Date de publication:
29 Oct 2024
Historique:
received: 09 07 2024
accepted: 03 10 2024
medline: 30 10 2024
pubmed: 30 10 2024
entrez: 30 10 2024
Statut: epublish

Résumé

Staphylococcus aureus clinical isolates with vancomycin MICs of 2 µg/ml have been associated with vancomycin therapeutic failure and the heterogenous vancomycin-intermediate S. aureus (hVISA) phenotype. While carriage of van genes has usually been associated with higher level of MIC and frank vancomycin resistance, the unrecognized risk of hetero-resistance is frequently underestimated. Methods used for assessing vancomycin susceptibility have also shown different concordance and variable performance and accessibility in routine clinical diagnostics posing a challenge to inform treatment selection in hospital settings. A total of 195 clinical samples were obtained among which 100 S. aureus isolates were identified. Ninety-six MRSA isolates have been identified using cefoxitin disc and mecA gene detection. The vanA and vanB genes have been screened for in the studied isolates using conventional PCR amplification. Examination of reduced vancomycin susceptibility has been performed using vancomycin screen agar, Broth Micro Dilution method (BMD), and VITEK2. Blood isolates were screened for hVISA using PAP-AUC method. Vancomycin screening agar applied to 96 MRSA isolates revealed 16 isolates with reduced vancomycin susceptibility. Further MIC testing revealed that 7 isolates were VISA and only 1 isolate was identified as VRSA using both BMD MIC method and VITEK2. Among 24 tested blood isolates, 4 isolates (16.7%) revealed the hVISA phenotype as identified using PAP-AUC method. Using PCR, vanA gene was identified in 5 S. aureus isolates (5%). Three of them were VSSA while the other two isolates were VISA. In this study, we report the very low prevalence of VRSA among the tested S. aureus clinical isolates (1%) and the existence of hVISA phenotype among studied S. aureus blood isolates at the rate of 16.7% in our setting. Fifty percent (8/16) of isolates that demonstrated reduced vancomycin susceptibility using vancomycin agar screen tested susceptible using both broth dilution method and VITEK2. These finding together with the concerning silent carriage of vanA gene among VSSA and VISA (5%) may underly hidden and uninvestigated factors contributing to vancomycin treatment failure that warrant cautious vancomycin prescription.

Sections du résumé

BACKGROUND BACKGROUND
Staphylococcus aureus clinical isolates with vancomycin MICs of 2 µg/ml have been associated with vancomycin therapeutic failure and the heterogenous vancomycin-intermediate S. aureus (hVISA) phenotype. While carriage of van genes has usually been associated with higher level of MIC and frank vancomycin resistance, the unrecognized risk of hetero-resistance is frequently underestimated. Methods used for assessing vancomycin susceptibility have also shown different concordance and variable performance and accessibility in routine clinical diagnostics posing a challenge to inform treatment selection in hospital settings.
METHODS METHODS
A total of 195 clinical samples were obtained among which 100 S. aureus isolates were identified. Ninety-six MRSA isolates have been identified using cefoxitin disc and mecA gene detection. The vanA and vanB genes have been screened for in the studied isolates using conventional PCR amplification. Examination of reduced vancomycin susceptibility has been performed using vancomycin screen agar, Broth Micro Dilution method (BMD), and VITEK2. Blood isolates were screened for hVISA using PAP-AUC method.
RESULTS RESULTS
Vancomycin screening agar applied to 96 MRSA isolates revealed 16 isolates with reduced vancomycin susceptibility. Further MIC testing revealed that 7 isolates were VISA and only 1 isolate was identified as VRSA using both BMD MIC method and VITEK2. Among 24 tested blood isolates, 4 isolates (16.7%) revealed the hVISA phenotype as identified using PAP-AUC method. Using PCR, vanA gene was identified in 5 S. aureus isolates (5%). Three of them were VSSA while the other two isolates were VISA.
CONCLUSION CONCLUSIONS
In this study, we report the very low prevalence of VRSA among the tested S. aureus clinical isolates (1%) and the existence of hVISA phenotype among studied S. aureus blood isolates at the rate of 16.7% in our setting. Fifty percent (8/16) of isolates that demonstrated reduced vancomycin susceptibility using vancomycin agar screen tested susceptible using both broth dilution method and VITEK2. These finding together with the concerning silent carriage of vanA gene among VSSA and VISA (5%) may underly hidden and uninvestigated factors contributing to vancomycin treatment failure that warrant cautious vancomycin prescription.

Identifiants

pubmed: 39472820
doi: 10.1186/s12879-024-10047-2
pii: 10.1186/s12879-024-10047-2
doi:

Substances chimiques

Vancomycin 6Q205EH1VU
Anti-Bacterial Agents 0
Bacterial Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1218

Informations de copyright

© 2024. The Author(s).

Références

Maple PAC, Hamilton-Miller JMT, Brumfitt W. World-wide antibiotic resistance in methicillin-resistant Staphylococcus aureus. Lancet. 1989;333:537–40.
doi: 10.1016/S0140-6736(89)90076-7
Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced Vancomycin susceptibility. J Antimicrob Chemother. 1997;40:135–6.
pubmed: 9249217 doi: 10.1093/jac/40.1.135
Shariati A, Dadashi M, Moghadam MT, van Belkum A, Yaslianifard S, Darban-Sarokhalil D. Global prevalence and distribution of Vancomycin resistant, Vancomycin intermediate and heterogeneously Vancomycin intermediate Staphylococcus aureus clinical isolates: a systematic review and meta-analysis. Sci Rep. 2020;10:12689.
pubmed: 32728110 pmcid: 7391782 doi: 10.1038/s41598-020-69058-z
Abdel-Maksoud M, El-Shokry M, Ismail G, Hafez S, El-Kholy A, Attia E, et al. Methicillin-Resistant Staphylococcus aureus recovered from Healthcare‐and Community‐Associated infections in Egypt. Int J Bacteriol. 2016;2016:5751785.
pubmed: 27433480 pmcid: 4940577 doi: 10.1155/2016/5751785
Amr GE, Al Gammal S. Emergence of Vancomycin resistant Staphylococcus aureus isolated from patients in ICUs of Zagazig University Hospitals. Egyptian Journal of Medical Microbiology. 2017;26.
ElSayed N, Ashour M, Amine AEK. Vancomycin resistance among Staphylococcus aureus isolates in a rural setting, Egypt. Germs. 2018;8:134.
pubmed: 30250832 pmcid: 6141221 doi: 10.18683/germs.2018.1140
Ibrahiem WAM, Rizk DE, Kenawy H, Hassan RHE. Prevalence of vancomycin resistance among clinical isolates of MRSA from different governorates in Egypt. Egypt J Med Microbiol. 2022;31:5–14.
doi: 10.21608/ejmm.2022.262673
Gohar NM, Balah MM, Sahloul N. Detection of Vancomycin Resistance among Hospital and Community-acquired Methicillin-resistant Staphylococcus aureus isolates. Egypt J Med Microbiol. 2023;32:45–52.
Azzam A, Khaled H, Mosa M, Refaey N, AlSaifi M, Elsisi S, et al. Epidemiology of clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and its susceptibility to linezolid and Vancomycin in Egypt: a systematic review with meta-analysis. BMC Infect Dis. 2023;23:263.
pubmed: 37101125 pmcid: 10134521 doi: 10.1186/s12879-023-08202-2
Belete MA, Gedefie A, Alemayehu E, Debash H, Mohammed O, Gebretsadik D, et al. The prevalence of Vancomycin-resistant Staphylococcus aureus in Ethiopia: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2023;12:86.
pubmed: 37649060 pmcid: 10468870 doi: 10.1186/s13756-023-01291-3
Foucault M-L, Courvalin P, Grillot-Courvalin C. Fitness cost of VanA-type Vancomycin resistance in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2009;53:2354–9.
pubmed: 19332680 pmcid: 2687198 doi: 10.1128/AAC.01702-08
Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis. 2001;1:147–55.
pubmed: 11871491 doi: 10.1016/S1473-3099(01)00091-3
Howden BP, Davies JK, Johnson PDR, 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. Clin Microbiol Rev. 2010;23:99–139.
pubmed: 20065327 pmcid: 2806658 doi: 10.1128/CMR.00042-09
Yan W, Hu Y, Ai X, Xu H, Sun T. Prevalence and clinical prognosis of heteroresistant Vancomycin-Intermediatestaphylococcus aureusin a tertiary care center in China. Chin Med J (Engl). 2013;126:505–9.
doi: 10.3760/cma.j.issn.0366-6999.20120812
Chong YP, Park K-H, Kim ES, Kim M-N, Kim S-H, Lee S-O, et al. Clinical and microbiologic analysis of the risk factors for mortality in patients with heterogeneous Vancomycin-intermediate Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2015;59:3541–7.
pubmed: 25845875 pmcid: 4432213 doi: 10.1128/AAC.04765-14
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. J Clin Microbiol. 2011;49:177–83.
pubmed: 21048008 doi: 10.1128/JCM.01128-10
Zhang S, Sun X, Chang W, Dai Y, Ma X. Systematic review and meta-analysis of the epidemiology of Vancomycin-intermediate and heterogeneous Vancomycin-intermediate Staphylococcus aureus isolates. PLoS ONE. 2015;10:e0136082.
pubmed: 26287490 pmcid: 4546009 doi: 10.1371/journal.pone.0136082
Rybak MJ, Vidaillac C, Sader HS, Rhomberg PR, Salimnia H, Briski LE, et al. Evaluation of Vancomycin susceptibility testing for methicillin-resistant Staphylococcus aureus: comparison of Etest and three automated testing methods. J Clin Microbiol. 2013;51:2077–81.
pubmed: 23596249 pmcid: 3697692 doi: 10.1128/JCM.00448-13
Brusamarello C, Daley AJ, Zhu X, Landersdorfer C, Gwee A. How important are MIC determination methods when targeting Vancomycin levels in patients with Staphylococcus aureus infections? J Antimicrob Chemother. 2021;76:1641–3.
pubmed: 33734365 doi: 10.1093/jac/dkab065
Chung H-S, Lee M. Different antimicrobial susceptibility testing methods to determine Vancomycin susceptibility and MIC for Staphylococcus aureus with reduced Vancomycin susceptibility. Diagnostics. 2022;12:845.
pubmed: 35453893 pmcid: 9032043 doi: 10.3390/diagnostics12040845
Swenson JM, Anderson KF, Lonsway DR, Thompson A, McAllister SK, Limbago BM, et al. Accuracy of commercial and reference susceptibility testing methods for detecting Vancomycin-intermediate Staphylococcus aureus. J Clin Microbiol. 2009;47:2013–7.
pubmed: 19420170 pmcid: 2708520 doi: 10.1128/JCM.00221-09
Rossatto FCP, Proença LA, Becker AP, Silveira AC, de O, Caierão J, D’azevedo PA. Evaluation of methods in detecting Vancomycin MIC among MRSA isolates and the changes in accuracy related to different MIC values. Rev Inst Med Trop Sao Paulo. 2014;56:469–72.
pubmed: 25351538 pmcid: 4296864 doi: 10.1590/S0036-46652014000600002
Agrawal C, Madan M, Pandey A, Thakuria B. Methicillin resistant Staphylococcus aureus: inconsistencies in Vancomycin susceptibility testing methods, limitations and advantages of each method. J Clin Diagn Res. 2015;9:DC01.
pubmed: 26557515 pmcid: 4625234
Diaz R, Ramalheira E, Afreixo V, Gago B. Evaluation of Vancomycin MIC creep in Staphylococcus aureus. J Glob Antimicrob Resist. 2017;10:281–4.
pubmed: 28751240 doi: 10.1016/j.jgar.2017.04.007
Kuo C-F, Lio CF, Chen H-T, Wang Y-TT, Ma KS-K, Chou YT, et al. Discordance of Vancomycin minimum inhibitory concentration for methicillin-resistant Staphylococcus aureus at 2 µg/mL between Vitek II, E-test, and broth microdilution. PeerJ. 2020;8:e8963.
pubmed: 32435531 pmcid: 7224226 doi: 10.7717/peerj.8963
Clinical and Laboratory Standards Institute. In: Wayne CL, editor. Performance standards for antimicrobial susceptibility testing. 34 ed. PA; 2024.
Maharjan M, Sah AK, Pyakurel S, Thapa S, Maharjan S, Adhikari N, et al. Molecular confirmation of vancomycin-resistant Staphylococcus aureus with vanA Gene from a hospital in Kathmandu. Int J Microbiol. 2021;2021:3847347.
pubmed: 34899917 pmcid: 8660244 doi: 10.1155/2021/3847347
D C-AB JWC, Michael DW. Novel screening Agar for detection of Vancomycin-Nonsusceptible Staphylococcus aureus. J Clin Microbiol. 2010;48:949–51.
doi: 10.1128/JCM.02295-09
Othman HB, Halim RMA, Gomaa FAM, Amer MZ. Vancomycin MIC distribution among methicillin-resistant Staphylococcus aureus. Is reduced Vancomycin susceptibility related to MIC creep? Open Access Maced. J Med Sci. 2019;7:12.
Harigaya Y, Ngo D, Lesse AJ, Huang V, Tsuji BT. Characterization of heterogeneous Vancomycin-intermediate resistance, MIC and accessory gene regulator (agr) dysfunction among clinical bloodstream isolates of staphyloccocus aureus. BMC Infect Dis. 2011;11:287.
pubmed: 22026752 pmcid: 3215976 doi: 10.1186/1471-2334-11-287
Xu J, Pang L, Ma XX, Hu J, Tian Y, Yang YL, et al. Phenotypic and molecular characterisation of Staphylococcus aureus with reduced Vancomycin susceptibility derivated in vitro. Open Med. 2018;13:475–86.
doi: 10.1515/med-2018-0071
Zarghami Moghaddam P, Azimian A, Sepahy A, Iranbakhsh A. Isolation and genetic characterization of vancomycin-resistant and mecC + methicillin-resistant Staphylococcus aureus strains in clinical samples of Bojnurd, Northeastern Iran. Jundishapur Journal of Microbiology. 2021;14.
Medhat ED, Magi M, Mohamed EN, El Sayed K, Mohamed EK. The first two vancomycin resistant Staphylococcus aureus isolates in Mansoura university hospital: epidemiology and antimicrobial study. 2008.
Shebl RI, Mosaad YO. Frequency and antimicrobial resistance pattern among bacterial clinical isolates recovered from different specimens in Egypt. Cent Afr J Public Heal. 2019;5:36–45.
Al-Ghareeb K, Abdel Gwad A, Gamal El Din M, Azmy A. PREVALENCE OF VANCOMYCIN RESISTANT STAPHYLOCOCCUS AUREUS (VRSA) IN SOME EGYPTIAN HOSPITALS. Al-Azhar J Pharm Sci. 2022;66:208–21.
doi: 10.21608/ajps.2022.269253
Tiwari HK, Sen MR. Emergence of Vancomycin resistant Staphylococcus aureus (VRSA) from a tertiary care hospital from northern part of India. BMC Infect Dis. 2006;6:1–6.
doi: 10.1186/1471-2334-6-156
Cong Y, Yang S, Rao X. Vancomycin resistant Staphylococcus aureus infections: a review of case updating and clinical features. J Adv Res. 2020;21:169–76.
pubmed: 32071785 doi: 10.1016/j.jare.2019.10.005
Elkhyat AH, Makled AF, Albeltagy AM, Keshk TF, Dawoud AM. Prevalence of vanA Gene among Methicillin Resistant S. aureus strains isolated from burn Wound infections in Menoufia University Hospitals. Egypt J Med Microbiol. 2020;29:97–104.
doi: 10.51429/EJMM29313
McGuinness WA, Malachowa N, DeLeo FR. Vancomycin resistance in Staphylococcus aureus. Yale J Biology Med. 2017;90:269–81.
Wilcox M, Al-Obeid S, Gales A, Kozlov R, Martínez-Orozco JA, Rossi F, et al. Reporting elevated Vancomycin minimum inhibitory concentration in methicillin-resistant Staphylococcus aureus: consensus by an International Working Group. Future Microbiol. 2019;14:345–52.
pubmed: 30724113 pmcid: 6479275 doi: 10.2217/fmb-2018-0346
Arthur M, Molinas C, Depardieu F, Courvalin P. Characterization of Tn1546, a Tn3-related transposon conferring glycopeptide resistance by synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol. 1993;175:117–27.
pubmed: 8380148 pmcid: 196104 doi: 10.1128/jb.175.1.117-127.1993
Weigel LM, Donlan RM, Shin DH, Jensen B, Clark NC, McDougal LK, et al. High-level Vancomycin-resistant Staphylococcus aureus isolates associated with a polymicrobial biofilm. Antimicrob Agents Chemother. 2007;51:231–8.
pubmed: 17074796 doi: 10.1128/AAC.00576-06
Périchon B, Courvalin P. Heterologous expression of the enterococcal vanA operon in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2004;48:4281–5.
pubmed: 15504853 pmcid: 525442 doi: 10.1128/AAC.48.11.4281-4285.2004
El-Aziz NKA, El-Hamid MIA, Bendary MM, El-Azazy AA, Ammar AM. Existence of vancomycin resistance among methicillin resistant S. aureus recovered from animal and human sources in Egypt. Slovenian Veterinary Research/Slovenski Veterinarski Zbornik. 2018;55.
Saadat S, Solhjoo K, Norooz-Nejad M-J, Kazemi A. VanA and vanB positive Vancomycin-resistant Staphylococcus aureus among clinical isolates in Shiraz, South of Iran. Oman Med J. 2014;29:335.
pubmed: 25337309 pmcid: 4202220 doi: 10.5001/omj.2014.90
Périchon B, Courvalin P. Synergism between β-lactams and glycopeptides against VanA-type methicillin-resistant Staphylococcus aureus and heterologous expression of the vanA operon. Antimicrob Agents Chemother. 2006;50:3622–30.
pubmed: 16954318 pmcid: 1635195 doi: 10.1128/AAC.00410-06
Audun S, Torunn P, Wik LK, Kåre B, Gresdal RT, Andreas R, et al. A silenced vanA Gene Cluster on a transferable plasmid caused an outbreak of Vancomycin-Variable Enterococci. Antimicrob Agents Chemother. 2016;60:4119–27.
doi: 10.1128/AAC.00286-16
Qureshi NK, Yin S, Boyle-Vavra S. The role of the Staphylococcal VraTSR Regulatory System on Vancomycin Resistance and vanA Operon expression in Vancomycin-Resistant Staphylococcus aureus. PLoS ONE. 2014;9:e85873.
pubmed: 24454941 pmcid: 3893269 doi: 10.1371/journal.pone.0085873
Sun W, Chen H, Liu Y, Zhao C, Nichols WW, Chen M, et al. Prevalence and characterization of heterogeneous Vancomycin-intermediate Staphylococcus aureus isolates from 14 cities in China. Antimicrob Agents Chemother. 2009;53:3642–9.
pubmed: 19546358 pmcid: 2737858 doi: 10.1128/AAC.00206-09
Castro BE, Berrio M, Vargas ML, Carvajal LP, Millan LV, Rios R, et al. Detection of heterogeneous Vancomycin intermediate resistance in MRSA isolates from Latin America. J Antimicrob Chemother. 2020;75:2424–31.
pubmed: 32562543 pmcid: 7443737 doi: 10.1093/jac/dkaa221
Amberpet R, Sistla S, Sugumar M, Nagasundaram N, Manoharan M, Parija SC. Detection of heterogeneous Vancomycin-intermediate Staphylococcus aureus: a preliminary report from south India. Indian J Med Res. 2019;150:194–8.
pubmed: 31670275 pmcid: 6829776 doi: 10.4103/ijmr.IJMR_1976_17
Khatib R, Jose J, Musta A, Sharma M, Fakih MG, Johnson LB, et al. Relevance of Vancomycin-intermediate susceptibility and heteroresistance in methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother. 2011;66:1594–9.
pubmed: 21525024 doi: 10.1093/jac/dkr169
van Hal SJ, Wehrhahn MC, Barbagiannakos T, Mercer J, Chen D, Paterson DL, et al. Performance of various testing methodologies for detection of heteroresistant Vancomycin-intermediate Staphylococcus aureus in bloodstream isolates. J Clin Microbiol. 2011;49:1489–94.
pubmed: 21270232 pmcid: 3122872 doi: 10.1128/JCM.02302-10
Lee MY, Lee WI, Kim MH, Kang SY, Kim YJ. Etest methods for screening heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA) strains. Curr Microbiol. 2020;77:3158–67.
pubmed: 32734419 doi: 10.1007/s00284-020-02123-y
Di Gregorio S, Perazzi B, Ordonez AM, De Gregorio S, Foccoli M, Lasala MB, et al. Clinical, microbiological, and genetic characteristics of heteroresistant Vancomycin-intermediate Staphylococcus aureus bacteremia in a teaching hospital. Microb Drug Resist. 2015;21:25–34.
pubmed: 25535825 pmcid: 4367492 doi: 10.1089/mdr.2014.0190
Nagwa R, Sherif Z. Heterogeneous Vancomycin intermediate resistance within methicillin-resistant staphylococcus aureus clinical isolates in Alexandria province. Egyptian Journal of Medical Microbiology. 2007.
Mashaly GE-S, El-Mahdy RH. Vancomycin heteroresistance in coagulase negative Staphylococcus blood stream infections from patients of intensive care units in Mansoura University Hospitals, Egypt. Ann Clin Microbiol Antimicrob. 2017;16:1–5.
doi: 10.1186/s12941-017-0238-5

Auteurs

Christine E Tawfeek (CE)

Medical Microbiology and Immunology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Sally Khattab (S)

Medical Microbiology and Immunology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Nermine Elmaraghy (N)

Medical Microbiology and Immunology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Anwar A Heiba (AA)

Medical Microbiology and Immunology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Wedad M Nageeb (WM)

Medical Microbiology and Immunology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. wedad_saleh@med.suez.edu.eg.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH