Sains Malaysiana 51(3)(2022): 865-872

http://doi.org/10.17576/jsm-2022-5103-20

Antibiotic Resistance Patterns of Coagulase-Negative Staphylococcus (CoNS) Isolates from a Major Teaching Hospital in Kuala Lumpur, Malaysia

(Corak Kerintangan Antibiotik Staphylococcus Koagulase-Negatif (CoNS) Dipencilkan daripada Hospital Pengajar Utama di Kuala Lumpur, Malaysia)

ASIF SUKRI^1,2, HAIFA HANANI MOHAMAD ZAKI² & NORAZIAH MOHAMAD ZIN^2,*

¹Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), 42300 UiTM Puncak Alam, Selangor Darul Ehsan, Malaysia

  ²Center for Diagnostic, Therapeutic and Investigative Studies (CODTIS), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Federal Territory, Malaysia

Diserahkan: 1 April 2021/Diterima: 29 Julai 2021

Abstract

Coagulase-negative Staphylococcus (CoNS) species is a leading cause of nosocomial infection in patients with indwelling medical devices and immunocompromised patients. This study was conducted to determine the antibiotic resistance pattern of CoNS isolated from a major teaching hospital in Malaysia. A total of 43 CoNS isolates were collected from August to October 2018 at Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia. Speciation of CoNS species was conducted by 16S rRNA sequencing. Antibiotic susceptibility test was performed using a standard procedure, and detection of staphylococcal cassette chromosome mec (SCCmec) elements and antibiotic resistance genes were conducted via multiplex polymerase chain reaction (PCR). Comparison of 16S rRNA sequences showed that 67.44% of the isolates were identified as S. epidermidis, followed by S. haemolyticus (11.63%), S. hominis (9.3%), S. capitis (4.65%), and other Staphylococcus sp. (6.98%).  All the CoNS isolates were susceptible to linezolid and tedizolid, while most of them were resistant towards penicillin (86.05%), cefoxitin (69.77%), erythromycin (72.02%), and 88.37% of them were resistant to at least 3 antibiotics. The majority of CoNS harboured nontypeable SCCmec elements. AacA-D (95.5%) and ermC (78.6%) were the most commonly detected antibiotic resistance genes while no detection of tetK, tetM and ermA genes were observed. This study showed a high prevalence of multidrug-resistant CoNS in HCTM healthcare settings. Understanding CoNS resistance mechanism is warranted for intervention strategy.

Keywords: Coagulase-negative Staphylococcus; multi-drug resistance; SCCmec typing

Abstrak

Spesies Staphylococcus koagulase-negatif (CoNS) merupakan penyebab utama jangkitan nosokomium dalam kalangan pesakit yang menggunakan peralatan perubatan dan pesakit yang terimunokompromi. Penyelidikan ini telah dijalankan untuk menentukan corak kerintangan antibiotik dalam CoNS yang dipencilkan daripada hospital pengajar utama di Malaysia. Sejumlah 43 pencilan CoNS telah diambil daripada Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur, Malaysia daripada Ogos sehingga Oktober 2018. Penentuan spesies CoNS telah dijalankan menggunakan penjujukan 16S rRNA. Ujian kerentanan antibiotik telah dijalankan menggunakan prosedur piawai manakala pengesanan kromosom kaset mec stafilokokus (SCCmec) dan gen rintangan antibiotik dijalankan menggunakan tindak balas berantai polimerase multipleks(PCR). Perbandingan penjujukan 16S rRNA menunjukkan 67.44% pencilan CoNS adalah S. epidermidis, diikuti S. haemolyticus (11.63%), S. hominis (9.3%), S. capitis (4.65%) dan Staphylococcus sp. yang lain (6.98%). Semua CoNS rentan terhadap Linezolid and Tedizolid, manakala hampir semua rintang terhadap Penisilin (86.05%), Cefoksitin (69.77%), Eritromisin (72.02%) dan 88.37% adalah rintang terhadap sekurang-kurangnya 3 antibiotik. Majoriti CoNS mempunyai unsur SCCmec yang tidak dapat ditentukan. AacA-D (95.5%) dan ermC (78.6%) merupakan gen kerintangan yang paling kerap dijumpai manakala gen tetK, tetM dan ermA tidak ditemui. Kajian ini menunjukkan prevalens CoNS rintang terhadap pelbagai antibiotik adalah tinggi dalam persekitaran HCTM. Pemahaman mekanisme kerintangan CoNS adalah penting untuk strategi intervensi.

Kata kunci: Kerintangan pelbagai antibiotik; pengetipan SCCmec; Staphylococcus koagulase-negatif

RUJUKAN

Argemi, X., Riegel, P., Lavigne, T., Lefebvre, N., Grandpré, N., Hansmann, Y., Jaulhac, B., Prévost, G. & Schramm, F. 2015. Implementation of matrix-assisted laser desorption ionization-time of flight mass spectrometry in routine clinical laboratories improves identification of coagulase-negative Staphylococci and reveals the pathogenic role of Staphylococcus lugdunensis. J. Clin. Microbiol. 53(7): 2030-2036.

Baig, S., Johannesen, T.B., Overballe-Petersen, S., Larsen, J., Larsen, A.R. & Stegger, M. 2018. Novel SCCmec type XIII (9A) identified in an ST152 methicillin-resistant Staphylococcus aureus. Infect. Genet. Evol. 61: 74-76.

Becker, K., Heilmann, C. & Peters, G. 2014. Coagulase-negative Staphylococci. Clin. Microbiol. Rev. 27(4): 871-926.

Castanheira, M., Watters, A.A., Bell, J.M., Turnidge, J.D. & Jones, R.N. 2010. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007-2008. Antimicrob. Agents Chemother. 54(9): 3614-3617.

Chabi, R. & Momtaz, H. 2019. Virulence factors and antibiotic resistance properties of the Staphylococcus epidermidis strains isolated from hospital infections in Ahvaz, Iran. Trop. Med. Health. 47: 56.

Chen, X.P., Li, W.G., Zheng, H., Du, H.Y., Zhang, L., Zhang, L., Che, J., Wu, Y., Liu, S.M. & Lu, J.X. 2017. Extreme diversity and multiple SCCmec elements in coagulase-negative Staphylococcus found in the clinic and community in Beijing, China. Ann. Clin. Microbiol. Antimicrob. 16(1): 57.

CLSI. 2017. Performance Standards for Antimicrobial Susceptibility Testing. 27th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute.

Foster, T.J. 2017. Antibiotic resistance in Staphylococcus aureus. Current status and future prospects. FEMS Microbiol. Rev. 41(3): 430‐449.

Ghaznavi-Rad, E., Nor Shamsudin, M., Sekawi, Z., van Belkum, A. & Neela, V. 2010. A simplified multiplex PCR assay for fast and easy discrimination of globally distributed staphylococcal cassette chromosome mec types in meticillin-resistant Staphylococcus aureus. J. Med. Microbiol. 59(Pt 10): 1135‐1139.

Gu, B., Kelesidis, T., Tsiodras, S., Hindler, J. & Humphries, R.M. 2013. The emerging problem of linezolid-resistant Staphylococcus. J. Antimicrob. Chemother. 68(1): 4-11.

Hebeisen, U.P., Atkinson, A., Marschall, J. & Buetti, N. 2019. Catheter-related bloodstream infections with coagulase-negative staphylococci: Are antibiotics necessary if the catheter is removed? Antimicrob. Resist. Infect. Control. 8: 21.

Hitzenbichler, F., Simon, M., Salzberger, B. & Hanses, F. 2017.  Clinical significance of coagulase-negative staphylococci other than S. epidermidis blood stream isolates at a tertiary care hospital. Infection 45(2): 179-186.

Ito, T., Kuwahara-Arai, K., Katayama, Y., Uehara, Y., Han, X., Kondo, Y. & Hiramatsu, K. 2014. Staphylococcal Cassette Chromosome mec (SCCmec) analysis of MRSA. Methods Mol. Biol. 1085: 131-148.

Ismail, M.A.H., Kamarudin, N., Abdul Samat, M.N., Raja Abdul Rahman, R.M.F., Saimun, S., Tan, T.L. & Neoh, H.M. 2021. Methicillin-Resistant Staphylococcus aureus (MRSA) clonal replacement in a Malaysian teaching hospital: Findings from an eight-year interval molecular surveillance. Antibiotics (Basel). 10(3): 320.

Knight, G.M., Budd, E.L., Whitney, L., Thornley, A., Al-Ghusein, H., Planche, T. & Lindsay, J.A. 2012. Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time. J. Antimicrob. Chemother. 67(10): 2514-2522.

Leski, T.A. & Tomasz, A. 2005.  Role of Penicillin-Binding Protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: Evidence for the cooperative functioning of PBP2, PBP4, and PBP2A. J. Bacteriol. 187(5): 1815-1824.

Liu, J., Chen, D., Peters, B.M., Li, L., Li, B., Xu, Z. & Shirliff, M.E. 2016. Staphylococcal chromosomal cassettes mec (SCCmec): A mobile genetic element in methicillin-resistant Staphylococcus aureus. Microbiol. Pathog. 101: 56-67.

Loncaric, I., Kübber-Heiss, A., Posautz, A., Ruppitsch, W., Lepuschitz, S., Schauer, B., Feßler, A.T., Krametter-Frötscher, R., Harrison, E.M., Holmes, M.A., Künzel, F., Szostak, M.P., Hauschild, T., Desvars-Larrive, A., Misic, D., Rosengarten, R., Walzer, C., Slickers, P., Monecke, S., Ehricht, R., Schwarz, S. & Spergser, J. 2019. Characterization of mecC gene-carrying coagulase-negative Staphylococcus spp. isolated from various animals. Vet. Microbiol. 230: 138-144.

Maleki, A., Ghafourian, S., Taherikalani, M. & Soroush, S. 2019. Alarming and threatening signals from health centers about multi drug resistance Staphylococcus haemolyticus. Infect. Disord. Drug Targets 19(2): 118-127.

Ministry of Health Malaysia. 2014. National Antibiotic Guideline. https://www.pharmacy.gov.my/v2/sites/default/files/document-upload/national-antibiotic-guideline-2014-full-versionjun2015_1.pdf

Nascimento, T.C., da Silva, V.L., Ferreira-Machado, A.B. & Diniz, C.G. 2015. Potential spread of multidrug-resistant coagulase-negative staphylococci through healthcare waste. J. Infect. Dev. Ctries. 9(1): 29-34.

National Center for Biotechnology Information. 2021. BLAST: Basic Local Alignment Search Tool. https://blast.ncbi.nlm.nih.gov/Blast.cgi Accessed on 30 March 2021.

Noordin, A., Sapri, H.F., Mohamad Sani, N.A., Leong, S.K., Tan, X.E., Tan, T.L., Mohamad Zin, N., Neoh, H.M. & Hussin, S. 2016. Antimicrobial resistance profiling and molecular typing of methicillin-resistant Staphylococcus aureus isolated from a Malaysian teaching hospital. J. Med. Microbiol. 65(12): 1476-1481.

Otto, M. 2013. Coagulase-negative staphylococci as reservoirs of genes facilitating MRSA infection: Staphylococcal commensal species such as Staphylococcus epidermidis are being recognized as important sources of genes promoting MRSA colonization and virulence. Bioessays 35(1): 4-11.

Reers, Y., Idelevich, E.A., Pätkau. H., Sauerland, M.C., Tafelski, S., Nachtigall, I., Berdel, W.E., Peters, G., Silling, G., Becker, K. & Molecular Diagnostics of Sepsis Study Group. 2016. Multiplex PCR assay underreports true bloodstream infections with coagulase-negative staphylococci in hematological patients with febrile neutropenia.  Diagn. Microbiol. Infect. Dis. 85(4): 413-415.

Riyaz-Ul-Hassan, S., Verma, V. & Qazi, G.N. 2008. Evaluation of three different molecular markers for the detection of Staphylococcus aureus by polymerase chain reaction. Food Microbiol. 25(3): 452-459.

Safarpoor Dehkordi, F., Gandomi, H., Basti, A.A., Misaghi, A. & Rahimi, E. 2017. Phenotypic and genotypic characterization of antibiotic resistance of methicillin-resistant Staphylococcus aureus isolated from hospital food. Antimicrob. Resist. Infect. Control. 6: 104.

Sani, N.A., Sapri, H.F., Noordin, A., Neoh, H-M. & Hussin, S. 2011. Species identification of coagulase negative Staphylococci (CoNS) isolates in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). APJMM. 1(1): 1-5.

Sani, N.A., Sapri, H.F., Neoh, H-M. & Hussin, S. 2014. First report on the molecular epidemiology of Malaysian Staphylococcus epidermidis isolated from a university teaching hospital. BMC Res. Notes. 7: 597.

Seng, R., Kitti, T., Thummeepak, R., Kongthai, P., Leungtongkam, U., Wannalerdsakun, S. & Sitthisak S. 2017.  Biofilm formation of methicillin-resistant coagulase negative staphylococci (MR-CoNS) isolated from community and hospital environments. PLoS ONE. 12(8): e0184172.

Sukri, A., Saat, M.N.F., Mohd Yusof, N.A., Zin, N.M. & Abdul Rachman, A.R. 2021. Differences in antibiotic resistance profiles of methicillin-susceptible and –resistant Staphylococcus aureus isolated from the teaching hospital in Kuala Lumpur, Malaysia. J. Appl. Biol. Biotechnol. 9(4): 98-103.

Weinstein, M.P., Towns, M.L., Quartey, S.M., Mirrett, S., Reimer, L.G., Parmigiani, G. & Reller, L.B. 1997. The clinical significance of positive blood cultures in the 1990s: A prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin. Infect. Dis. 24(4): 584-602.

^*Pengarang untuk surat-menyurat; email: noraziah.zin@ukm.edu.my