Methicillin resistant Staphylococcus aureus - importance of appropriate empirical therapy in serious infections
DOI:
https://doi.org/10.18203/2349-3933.ijam20214882Keywords:
Methicillin-resistant Staphylococcus aureus, Prevalence, Appropriate empiric therapy, Anti-MRSA agents, LevonadifloxacinAbstract
India has been titled the capital of antimicrobial resistance in the world with the centre for disease dynamics, economics and policy (CDDEP) predicting two million deaths in India by 2050. As per the World Health Organisation’s global priority pathogen list of 2017, methicillin resistant Staphylococcus aureus (MRSA) has been classified as a ‘high priority’ pathogen due to its association with increased mortality rate, rising prevalence of resistance and increased burden on healthcare settings. A recent report by Indian Council of Medical Research signifies the exponential rise in the prevalence of MRSA in India, from 29% in 2009 to 39% in 2018. Serious MRSA infections are commonly associated with poor clinical outcomes coupled with increased hospitalisation stay and cost. Therefore, early identification and appropriate empiric treatment of MRSA plays a crucial role in healthcare settings. However, the constant rise in multi-drug resistance to the currently available anti-MRSA agents as well as their compromised safety profile limits its clinical use to manage severe MRSA infections. This review article explores the implications of severe MRSA infections and inappropriate empirical therapy on the clinical as well as economic outcomes. In addition, it also highlights limitations of the currently available anti-MRSA agents and the need for newer agents to manage multi drug resistant (MDR) gram positive infections.
References
Abou Fayad A, Itani D, Miari M, Tanelian A, Iweir S, Matar GM. From bugs to drugs: Combating antimicrobial resistance by discovering novel antibiotics. J Infect Dev Ctries. 2018;12(2.1):3.
Hassoun A, Linden PK, Friedman B. Incidence, prevalence, and management of MRSA bacteremia across patient populations-a review of recent developments in MRSA management and treatment. Crit Care. 2017;21(1):211.
Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis. 2003;36(1):53-9.
Shurland S, Zhan M, Bradham DD, Roghmann MC. Comparison of mortality risk associated with bacteremia due to methicillin-resistant and methicillin-susceptible Staphylococcus aureus. Infect Control Hospital Epidemiol. 2007;28(3):273-9.
World Health Organization. Antimicrobial resistance-Global Report on Surveillance. Available at: https://apps.who.int/iris/bitstream/handle/10665/ 112642/9789241564748_eng.pdf;jsessionid=706BB0FB86C3CF02B0082119E4BCFD32?sequence=1. Accessed on 15 May 2020.
AMRSN Annual Report. Indian Council of Medical Research. Available at: https://www.icmr.nic.in/ sites/default/files/reports/AMRSN_Annual_Report_2018_0.pdf. Accessed on 14 April 2020.
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):18-55.
Nathwani D, Morgan M, Masterton RG, Dryden M, Cookson BD, French G, et al. Guidelines for UK practice for the diagnosis and management of methicillin-resistant Staphylococcus aureus (MRSA) infections presenting in the community J Antimicrob Chemother. 2008;61(5):976-94.
Indian Network for Surveillance of Antimicrobial Resistance (INSAR) group, India. Methicillin resistant Staphylococcus aureus (MRSA) in India: Prevalence & susceptibility pattern. Indian J Med Res. 2013;137:363-9.
Kumar M. Multidrug-resistant Staphylococcus aureus, India, 2013–2015. Emerg Infect Dis. 2016;22(9):1666-7.
Mohanty S, Behera B, Sahu S, Praharaj AK. Recent pattern of antibiotic resistance in Staphylococcus aureus clinical isolates in Eastern India and the emergence of reduced susceptibility to vancomycin. J Lab Physicians. 2019;11(4):340-5.
Husain A, Rawat V, Umesh, Kumar M, Verma PK. Vancomycin, linezolid and daptomycin susceptibility pattern among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) from Sub- Himalyan Center. J Lab Physicians. 2018;10(2):145-8.
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.
Goering RV, Shawar RM, Scangarella NE, O'Hara FP, Amrine-Madsen H, West JM, et al. Molecular epidemiology of methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates from global clinical trials. J Clin Microbiol. 2008;46(9):2842-7.
Steinig EJ, Andersson P, Harris SR, Sarovich DS, Manoharan A, Coupland P, et al. Single-molecule sequencing reveals the molecular basis of multidrug-resistance in ST772 methicillin-resistant Staphylococcus aureus. BMC Genomics. 2015;16(1):388.
Chakrakodi B, Prabhakara S, Nagaraj S, J. Etienne, G. Arakere. High Prevalence of Ciprofloxacin Resistance in Community Associated Staphylococcus aureus in a Tertiary Care Indian Hospital. Adv Microbiol. 2014;4(2):133-41.
Steinig EJ, Duchene S, Robinson DA, Monecke S, Yokoyama M, Laabei M, et al. Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent. mBio. 2019;10(6):e01105-19.
Gupta S, Mishra B, Thakur A, Dogra V, Loomba PS, Jain M, et al. Risk factors associated with MRSA. Southern Af J Infect Dis. 2018;33(3):76-9.
Chatterjee A, Rai S, Guddattu V, Mukhopadhyay C, Saravu K. Is methicillin-resistant Staphylococcus Aureus infection associated with higher mortality and morbidity in hospitalized patients? A cohort study of 551 patients from South Western India. Risk Manag Healthc Policy. 2018;11:243-50.
Hershow RC, Khayr WF, Smith NL. A comparison of clinical virulence of nosocomially acquired methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections in a university hospital. Infect Control Hosp Epidemiol. 1992;13(10):587-93.
Engemann JJ, Carmeli Y, Cosgrove SE, Fowler VG, Bronstein MZ, Trivette SL, et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin Infect Dis. 2003;36(5):592-8.
Siddiqui AH, Koirala J. Methicillin Resistant Staphylococcus Aureus (MRSA). In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2020.
Hanberger H, Walther S, Leone M, Barie PS, Rello J, Lipman J, et al. Increased mortality associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in the intensive care unit: results from the EPIC II study. Int J Antimicrob Agents. 2011;38(4):331-5.
Chen SY, Wang JT, Chen TH, Lai MS, Chie WC, Chien KL, et al. Impact of traditional hospital strain of methicillin-resistant Staphylococcus aureus (MRSA) and community strain of MRSA on mortality in patients with community-onset S aureus bacteremia. Medicine (Baltimore). 2010;89(5):285-94.
Combs K, Cox K. Clinical outcomes involving patients that develop septic arthritis with methicillin sensitive staphylococcus aureus versus methicillin resistant staphylococcus aureus. J Orthop. 2017;15(1):9-12.
Anderson DJ, Kaye KS, Chen LF, Schmader KE, Choi Y, Sloane R, et al. Clinical and financial outcomes due to methicillin resistant Staphylococcus aureus surgical site infection: a multi-center matched outcomes study. PLoS One. 2009;4(12):e8305.
Cosgrove SE, Qi Y, Kaye KS, Harbarth S, Karchmer AW, Carmeli Y. The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges. Infect Control Hosp Epidemiol. 2005;26(2):166-74.
de Kraker ME, Davey PG, Grundmann H. Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe. PLoS Med. 2011;8(10):e1001104.
Andreassen AES, Jacobsen CM, de Blasio B, White R, Kristiansen IS, Elstrøm P. The impact of methicillin-resistant S. aureus on length of stay, readmissions and costs: a register based case-control study of patients hospitalized in Norway. Antimicrob Resist Infect Control. 2017;6:74.
Macedo-Viñas M, De Angelis G, Rohner P, Safran E, Stewardson A, Fankhauser C, et al. Burden of meticillin-resistant Staphylococcus aureus infections at a Swiss University hospital: excess length of stay and costs. J Hosp Infect. 2013;84(2):132-7.
Zhen X, Lundborg CS, Zhang M, Sun X, Li Y, Hu X, et al. Clinical and economic impact of methicillin-resistant Staphylococcus aureus: a multicentre study in China. Sci Rep. 2020;10:3900.
Wilke M, Hübner C, Kämmerer W. Calculated parenteral initial treatment of bacterial infections: Economic aspects of antibiotic treatment. GMS Infect Dis. 2020;8:3.
Treatment Guidelines. Available at: http://www. ijmm.org/documents/Treatment_Guidelines_2019_Final.pdf. Accessed on 20 May 2020.
Khilnani GC, Zirpe K, Hadda V, Mehta Y, Madan K, Kulkarni A, et al. Guidelines for Antibiotic Prescription in Intensive Care Unit. Indian J Crit Care Med. 2019;23(1):1-63.
Singhal T. "Rationalization of Empiric Antibiotic Therapy" - A Move Towards Preventing Emergence of Resistant Infections. Indian J Pediatr. 2020;87(11):945-50.
Robineau O, Robert J, Rabaud C, Bedos JP, Varon E, Péan Y, et al. Management and outcome of bloodstream infections: a prospective survey in 121 French hospitals (SPA-BACT survey). Infection and drug resistance. 2018;11:1359.
Marquet K, Liesenborgs A, Bergs J, Vleugels A, Claes N. Incidence and outcome of inappropriate in-hospital empiric antibiotics for severe infection: a systematic review and meta-analysis. Crit Care. 2015;19(1):63.
Kim SH, Park WB, Lee CS, Kang CI, Bang JW, Kim HB, et al. Outcome of inappropriate empirical antibiotic therapy in patients with Staphylococcus aureus bacteraemia: analytical strategy using propensity scores. Clin Microbiol Infect. 2006;12(1):13-21.
Nickerson EK, Wuthiekanun V, Wongsuvan G, Limmathurosakul D, Srisamang P, Mahavanakul W, et al.Factors Predicting and Reducing Mortality in Patients with Invasive Staphylococcus aureus Disease in a Developing Country. PLoS One. 2009;4(8):e6512.
Paul M, Kariv G, Goldberg E, Raskin M, Shaked H, Hazzan R, et al. Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother. 2010;65(12):2658-65.
Schweizer ML, Furuno JP, Harris AD, Johnson JK, Shardell MD, McGregor JC, et al. Empiric antibiotic therapy for Staphylococcus aureus bacteremia may not reduce in-hospital mortality: a retrospective cohort study. PloS one. 2010;5(7):e11432.
Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54(11):4851-63.
Wi YM, Rhee JY, Kang CI, Chung DR, Song JH, Peck KR. Clinical predictors of methicillin-resistance and their impact on mortality associated with Staphylococcus aureus bacteraemia. Epidemiol Infect. 2018;146(10):1326-36.
Zilberberg MD, Shorr AF, Micek ST, Chen J, Ramsey AM, Hoban AP, et al. Inappropriate Treatment of HCA‐cSSTI. J Hosp Med. 2010;9;535-40.
Shorr AF, Micek ST, Kollef MH. Inappropriate therapy for methicillin-resistant Staphylococcus aureus: resource utilization and cost implications. Crit Care Med. 2008;36(8):2335-40.
Chong YP, Bae IG, Lee SR, Chung JW, Jun JB, Choo EJ, et al. Clinical and economic consequences of failure of initial antibiotic therapy for patients with community-onset complicated intra-abdominal infections. PLoS One. 2015;10(4):e0119956.
Szumowski JD, Cohen DE, Kanaya F, Mayer KH. Treatment and outcomes of infections by methicillin-resistant Staphylococcus aureus at an ambulatory clinic. Antimicrob Agents Chemother. 2007;51(2):423-8.
Khawcharoenporn T, Tice A. Empiric outpatient therapy with trimethoprim-sulfamethoxazole, cephalexin, or clindamycin for cellulitis. Am J Med. 2010;123(10):942-50.
Bakthavatchalam YD, Rao SV, Isaac B, Manesh A, Nambi S, Swaminathan S, et al. A comparative assessment of clinical, pharmacological and antimicrobial profile of novel anti-methicillin-resistant Staphylococcus aureus agent levonadifloxacin: Therapeutic role in nosocomial and community infections. Indian J Med Microbiol. 2019;37:478-87.
Cosimi RA, Beik N, Kubiak DW, Johnson JA. Ceftaroline for Severe Methicillin-Resistant Staphylococcus aureus Infections: A Systematic Review. Open Forum Infect Dis. 2017;4(2):84.
Riccobene TA, Pushkin R, Jandourek A, Knebel W, Khariton T. Penetration of ceftaroline into the epithelial lining fluid of healthy adult subjects. Antimicrob Agents Chemother. 2016;60:5849-57.
Tellis M, Joseph J, Khande H, Bhagwat S, Patel M. In vitro bactericidal activity of levonadifloxacin (WCK 771) against methicillin-and quinolone-resistant Staphylococcus aureus biofilms. J Med Microbiol. 2019;26:1-8.
Bhagwat SS, Nandanwar M, Kansagara A, Patel A, Takalkar S, Chavan R, et al. Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence. Drug Design, Development and Therapy. 2019;13:4351.
Rodvold KA, Gotfried MH, Chugh R, Gupta M, Yeole R, Patel A, et al. Intrapulmonary Pharmacokinetics of Levonadifloxacin following Oral Administration of Alalevonadifloxacin to Healthy Adult Subjects. Antimicrob Agents Chemother. 2018;62(3):e02297-17.
Patel A, Sangle GV, Trivedi J, Shengule SA, Thorve D, Patil M, et al. Levonadifloxacin, a Novel Benzoquinolizine Fluoroquinolone, Modulates Lipopolysaccharide-Induced Inflammatory Responses in Human Whole-Blood Assay and Murine Acute Lung Injury Model. Antimicrob Agents Chemother. 2020;64(5):e00084-20.
Andersson M, Östholm-Balkhed Å, Fredrikson M, Holmbom M, Hällgren A, Berg S, et al. Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting. Eur J Clin Microbiol Infect Dis. 2019;38(7):1223-34.
Watanakunakorn C. Mode of action and in-vitro activity of vancomycin. J Antimicrob Chemother. 1984;14:7-18.
Vancomycin 1 g Powder for Solution [package insert on the internet]. Wrexham (United Kingdom): Wockhardt UK Ltd. 2008. Available at: https://www.medicines.org.uk/emc/product/6255#gref. Accessed on 14 January 2021.
Parenti F. Structure and mechanism of action of teicoplanin. J Hosp Infect. 1986;7:79-83.
Targocid 200 mg powder [package insert on the internet]. Berkshire (UK): Aventis Pharma Limited. 1989. Available at: https://www.medicines.org. uk/emc/product/2926/smpc#gref. Accessed on 29 July 2021.
Hashemian SMR, Farhadi T, Ganjparvar M. Linezolid: a review of its properties, function, and use in critical care. Drug Des Devel Ther. 2018;12:1759-67.
Zyvox 600 mg film-coated tablets [package insert on the internet]. Kent: Pfizer Limited. 2001. Available at: https://www.medicines.org.uk/emc/medicine/98 57#gref. Accessed on 29 September 2021.
Miller WR, Bayer AS, Arias CA. Mechanism of Action and Resistance to Daptomycin in Staphylococcus aureus and Enterococci. Cold Spring Harb Perspect Med. 2016;6(11):a026997.
Daptomycin 350 mg powder [package insert on the internet]. Middlesex (UK): Accord Healthcare Limited. 2020. Available at: https://www.medicines. org.uk/emc/product/8766/smpc#gref. Accessed on 28 October 2021.
Greer ND. Tigecycline (Tygacil): the first in the glycylcycline class of antibiotics. Proc (Bayl Univ Med Cent). 2006;19(2):155-61.
Tygacil 50 mg powder [package insert on the internet]. Bruxelles (Belgium): Pfizer Europe. 2006. Available at: https://www.medicines.org.uk/emc/ medicine/17779/SPC/Tygacil+50mg+powder+for+solution+for+infusion/#gref. Accessed on 29 March 2021.
Murphy PB, Bistas KG, Le JK. Clindamycin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2021. Accessed on 01 July 2021.
Clindamycin 150 mg Capsules [package insert on the internet]. Surrey (UK): Sandoz Limited. 2002. Available at: https://www.medicines.org.uk/emc/ medicine/21628#gref. Accessed on 19 August 2021.
Wehrli W. Rifampin: mechanisms of action and resistance. Rev Infect Dis. 1983;5:407-11.
Rifampicin 300 mg Capsules [package insert on the internet]. Hertfordshire (UK): Generics [UK] Limited t/a Mylan. 1986. Available at: https://www.medicines.org.uk/emc/product/8789/smpc#gref. Accessed on 03 December 2021.
Duplessis C, Crum-Cianflone NF. Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA). Clin Med Rev Ther. 2011;3:a2466.
Zinforo 600 mg powder [package insert on the internet]. County Cork (Ireland): Pfizer Ireland Pharmaceuticals. 2012. Available at: https://www. ema.europa.eu/en/documents/product-information/ zinforo-epar-product-information_ en.pdf. Accessed on 24 April 2021.