Methicillin resistant Staphylococcus aureus: a review of the present Indian scenario and drug treatment
Keywords:Altered penicillin-binding protein, Endocarditis, Linezolid, Methicillin-resistant S. aureus, Toxic shock syndrome
Methicillin-resistant strains of S. aureus cause infections that are associated with higher mortality rates and increased length of hospital stays, than infections caused by methicillin-susceptible strains. The mechanism by which MRSA strains develop resistance is by the production of an altered penicillin-binding protein (PBP), which has a decreased affinity for most semisynthetic penicillins. MRSA has increased in prevalence and has become endemic in the Indian subcontinent, with incidence varying from 25% in Western regions to 50% in Southern India. A multi-centric study conducted across 15 tertiary care centers in India from 2008 to 2009 showed overall prevalence of MRSA infection to be 41% among S. aureus isolates, and recent Indian studies from 2014 and 2018 have also suggested an increasing prevalence of MRSA. Transmission is mainly horizontal and concerns high risk populations (patients with prolonged hospital stay, on haemodialysis, receiving cancer treatment or specific medications that affect immune function, intravenous drug users and individuals who have had surgery in the recent past. Community Acquired MRSA has emerged as significant pathogen responsible for potentially fatal infections including life-threatening pneumonia, necrotizing fasciitis, endocarditis, osteomyelitis, severe sepsis, and toxic shock syndrome. Diagnosis is mainly by gram stain, culture and quantitative PCR. Newer techniques include Multi-locus sequence typing (MLST), Pulsed-field gel electrophoresis (PFGE), Bacteriophage typing, spa locus typing and SCCmec typing. Although Vancomycin was previously considered the definitive treatment for serious MRSA infections, the emergence of less-susceptible strains, poor clinical outcomes, and increased nephrotoxicity with high-dose therapy have deterred its use as first-line therapy in many cases. Although a number of new and effective antimicrobial agents are now available for the treatment of MRSA, their exact role and choice of agent needs to be well-defined.
Gould D, Chamberlaine A. Staphylococcus aureus: a review of the literature. J Clin Nurs 1995;4:5-12.
Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, Nouwen JL. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis 2005;5:751-62.
Williams RE, Jevons MP, Shooter RA, Hunter CJ, Girling JA, Griffiths JD, Taylor GW. Nasal staphylococci and sepsis in hospital patients. Br Med J 1959;2:658-62.
Kirby WM. Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science 1944;99:452-3.
Jevons MP. “Celbenin”-resistant staphylococci. Br Med J. 1961;1:124-5.
Wolk DM, Struelens MJ, Pancholi P, Davis T, Della-Latta P, Fuller D, et al. Rapid detection of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in wound specimens and blood cultures: multicenter preclinical evaluation of the Cepheid Xpert MRSA/SA skin and soft tissue and blood culture assays. J Clin Microbiol. 2009;47:823-6.
Fortuin-de Smidt MC, Singh-Moodley A, Badat R, Quan V, Kularatne R, Nana T, et al. for GERMS-SA. Staphylococcus aureus bacteraemia in Gauteng academic hospitals, South Africa. Int J Infect Dis. 2015;30:41-8.
Thampi N, Showler A, Burry L, Bai AD, Steinberg M, Ricciuto DR, et al. Multicenter study of health care cost of patients admitted to hospital with Staphylococcus aureus bacteremia: impact of length of stay and intensity of care. Am J Infect Control 2015;43:739-44.
Utsui Y, Yokota T. Role of an altered penicillin-binding protein in methicillin- and cephem-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1985;28:397-403.
Matsuhashi M, Song MD, Ishino F, Wachi M, Doi M, Inoue M, et al. Molecular cloning of the gene of a penicillin-binding protein supposed to cause high resistance to beta-lactam antibiotics in Staphylococcus aureus. J Bacteriol. 1986;167:975-80.
Katayama Y, Ito T, Hiramatsu K. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 2000;44:1549-55.
Diekema DJ, Pfaller MA, Schmitz FJ, Smayevsky J, Bell J, Jones RN, et al. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis. 2001;32(2):S114-32.
Sader HS, Farrell DJ, Jones RN. Antimicrobial susceptibility of Gram-positive cocci isolated from skin and skin-structure infections in European medical centres. Int J Antimicrob Agents. 2010;36:28-32.
Tracy LA, Furuno JP, Harris AD, Singer M, Langenberg P, Roghmann MC. Staphylococcus aureus infections in US veterans, Maryland, USA, 1999-2008. Emerg Infect Dis. 2011;17:441-8.
Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, et al. National Healthcare Safety Network Team; Participating National Healthcare Safety Network Facilities. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol. 2008;29(11):996-1011.
Dukic VM, Lauderdale DS, Wilder J, Daum RS, David MZ. Epidemics of community-associated methicillin-resistant Staphylococcus aureus in the United States: a meta-analysis. PLoS One. 2013;8(1):e52722.
Patel AK, Patel KK, Patel KR, Shah S, Dileep P. Time trends in the epidemiology of microbial infections at a tertiary care center in west India over last 5 years. J Assoc Physicians India. 2010;58(Suppl):37-40.
Gopalakrishnan R, Sureshkumar D. Changing trends in antimicrobial susceptibility and hospital acquired infections over an 8 year period in a tertiary care hospital in relation to introduction of an infection control programme. J Assoc Physicians India. 2010;58(Suppl):25-31.
Joshi S, Ray P, Manchanda V, Bajaj J, Chitnis D, Gautam V, et al. Methicillin resistant Staphylococcus aureus (MRSA) in India: prevalence & susceptibility pattern. Indian J Med Res. 2013;137(2):363.
Wattal C, Goel N, Oberoi JK, Raveendran R, Datta S, Prasad KJ. Surveillance of multidrug resistant organisms in tertiary care hospital in Delhi, India. J Assoc Physicians India. 2010;58(Suppl):32-6.
Gadepalli R, Dhawan B, Kapil A, Sreenivas V, Jais M, Gaind R, et al. Clinical and molecular characteristics of nosocomial methicillin-resistant Staphylococcus aureus skin and soft tissue isolates from three Indian hospitals. J Hosp Infect. 2009;73:253-63.
D’Souza N, Rodrigues C, Mehta A. Molecular characterization of Methicillin-resistant Staphylococcus aureus with emergence of epidemic clones of sequence type (ST)22 and ST 772 in Mumbai, India. J Clin Microbiol. 2010;48:1806-11.
Chatterjee SS, Ray P, Aggarwal A, Das A, Sharma M. A community based study on nasal carriage of Staphylococcus aureus. Indian J Med Res. 2009;130:742-8.
Mantri R, Karyakarte A, Ambhore N, Kombade S. Prevalence of Methicillin Resistant Staphylococcus aureus in tertiary care hospital, Central India. Int J Curr Microbiol App Sci. 2014;3(10):582-6.
Singh AK, Agarwal L, Kumar A, Sengupta C, Singh RP. Prevalence of nasal colonization of methicillin-resistant Staphylococcus aureus among schoolchildren of Barabanki district, Uttar Pradesh, India. J Family Med Prim Care 2018;7:162-6.
Monecke S, Coombs G, Shore AC, Coleman DC, Akpaka P, Borg M, et al. A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PloS one. 2011;6(4).
Naves K, Trindade N, Filho P. Methicillin-resistant Staphylococcus aureus bloodstream infection: risk factors and clinical outcome in non-intensive-care units. Revista da Sociedade Brasileira de Medicina Tropical. 2012;45(2):189-93.
Grema HA, Geidam YA, Gadzama GB, Ameh JA, Suleiman A. Methicillin resistant Staphylococcus aureus (MRSA): a review. Adv Anim Vet Sci. 2015;3(2):79-98.
Köck R, Becker K, Cookson B, van Gemert-Pijnen JE, Harbarth S, Kluytmans JA, et al. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Euro Surveillance. 2010;15(41).
Cooper BS, Medley GF, Stone SP, Kibbler CC, Cookson BD. Methicillin resistant Staphylococcus aureus in hospitals and the community: stealth dynamics and control catastrophes. Proc Natl Acad Sci. 2004;101(27):10223-8.
The National Institute for Occupational Safety and Health (NIOSH). Centers for Disease Control and Prevention (CDC). MRSA and the Workplace. Page last reviewed: August 17, 2015. Available at: https://www.cdc.gov/niosh/topics/mrsa/default.html. Accessed 15 January 2020.
Mayo Clinic. MRSA Infection: Symptoms and Causes. Page last reviewed: Oct. 18, 2018. Available at: https://www.mayoclinic.org/diseases-conditions/mrsa/symptoms-causes/syc-20375336. Accessed 18 January 2020.
Lambert M. IDSA Guidelines on the Treatment of MRSA Infections in Adults and Children. Am Fam Physician. 2011 Aug 15;84(4):455-63.
Nichols H. MRSA: Causes, Symptoms, Prevention and Treatments. Medical News Today. 2015. Available at: http://www.medicalnewstoday.com/articles/10634.php.
Pallin DJ, Binder WD, Allen MB, Lederman M, Parmar S, Filbin MR et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis 2013;56:1754.
Lee BK, Crossley K, Gerding DN. The association between Staphylococcus aureus bacteremia and bacteriuria. Am J Med 1978;65:303.
Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, Kirby A, Tilley R, Török ME et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis 2011;11:208.
Cosgrove SE, Vigliani GA, Campion M, Fowler VG, Abrutyn E, Corey GR, et al. Initial low dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis 2009;48:713.
Heldman AW, Hartert TV, Ray SC, Daoud EG, Kowalski TE, Pompili VJ et al. Oral antibiotic treatment of right sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med 1996;101:68.
Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A et al. Linezolid in methicillin resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 2012;54:621.
Liu C, Bayer A, Cosgrove S, Daum R, Fridkin S, Gorwitz R 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. IDSA Guidelines. Clin Infect Dis Advance Access. 2011.
Beckham JD, Tyler KL. Neuro-Intensive Care of Patients with Acute CNS Infections. Neurotherapeutics. 2012;9:124-38.
Francois P, Schrenzel J. Rapid Diagnosis and Typing of Staphylococcus aureus . Staphylococcus: Molecular Genetics. Caister Academic Press. 2008.
Mackay IM. Real-Time PCR in Microbiology: From Diagnosis to Characterization. Caister Academic Press. 2007.
Deurenberg RH, Stobberingh EE. The evolution of Staphylococcus aureus. Infect Genet Evol. 2008;8(6):747-63.
Kim J. Understanding the Evolution of Methicillin-Resistant Staphylococcus aureus. Clin Microbiol Newsl. 2009;31(3):17-23.
Rodvold KA, McConeghy KW. Methicillin-Resistant Staphylococcus aureus Therapy: Past, Present, and Future. Clin Infect Dis. 2014;58(S1):S20-7.
Craig WA. Basic pharmacodynamics of anti-bacterials with clinical applications to the use of beta-lactams, glycopeptides, and linezolid. Infect Dis Clin North Am. 2003;17(3):479-501.
Holmes NE, Tong SY, David JS, Van Hal SJ. Treatment of methicillin-resistant Staphylococcus aureus: vancomycin and beyond. Semin Respir Crit Care Med. 2015;36(1):17-30.
Choo EJ, Chambers HF. Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia. Infect Chemother. 2016;48(4):267-73.
Klevens RM, Morrison MA, Nadle J et al. Invasive methicillin resistant Staphylococcus aureus infections in the United States. JAMA 2007;298:1763-71.