Methicillin-resistant Staphylococcus aureus (MRSA) Infections

Author: Helia Mansouri Dana

Editor: Leslie Pineda

 

Overview 

Methicillin-resistant Staphylococcus aureus infections constitute a wide variety of infections in the body caused by the antibiotic-resistant form of the bacterium Staphylococcus aureus (S. aureus), normally found in the flora of the nasal cavities (Lee et al., 2018).

Specific strains of S. aureus have acquired the staphylococcal chromosomal cassette mec (SCCmec), which contains a methicillin-resistant gene, via horizontal gene transfer (Katayama et al., 2000).

MRSA infections culminated in the 1960s, immediately following the discovery and usage of methicillin, an antibiotic of the 𝛽-lactam family, however, there is rising evidence that their increased abundance is related to overuse of penicillin rather than usage of methicillin itself (Katayama et al., 2000; Lee et al., 2018).

MRSA can cause infective endocarditis (IE), septic arthritis, infections of the skin, device-related infections, and most importantly, they are the leading cause of bacteremia, a precursor to septic shock and other infections with high mortality rates (Tong et al., 2015). MRSA infection prevalence varies greatly across the globe, and it is typically classified into two main types:

• Community-acquired MRSA – acquired outside healthcare setting in healthy individuals and typically seen as skin infections
• Hospital-acquired MRSA – acquired in health-care settings, as post-op or device-related infections

(Tong et al., 2015)

 

Etiology

MRSA infections are caused by a member of the Staphylococcus genus, Staphylococcus aureus, which through horizontal gene transfer have acquired a DNA chromosomal cassette that provides them with a gene for resistance against antibiotics of the 𝛽-lactam family, including methicillin (Katayama et al., 2000).

S. aureus is naturally found in the microbiota of the nasal cavities in 30% of the population (Krismer et al., 2017). Commensal bacteria can become pathogenic if they gain access to the underlying tissues in their habitat, or via entry into the blood, leading to bacteremia (Tong et al., 2015).

Additionally, these bacteria may persist in other environments, such as those in hospitals, and be largely transmitted to patients during recovery after procedures by the health care staff (Fernando et al., 2017). 

 

Symptoms

• Large blisters on extremities or face that progress to dried scabs (skin infections by MRSA)
• Swollen, red, painful joints (Septic arthritis by MRSA)
• Inflammation at site of device insertion or attachment (Device-related MRSA infections)
• Erythema, increase in fibrous elements in tissue, pus formation at site of device insertion or attachment (Device-related MRSA infections)
• Systemic symptoms such as fever (bacteremia or other types of MRSA infections)
• Coughing, sore throat, and pus-filled air sacs (pneumonia by MRSA)

(Tong et al., 2015)

You might like to read about the Misdiagnosis Association MARI Research Institution.

Risk Factors

• Locations with high prevalence of MRSA: hospitals and intensive care units
• Prior colonization with MRSA strains (i.e. individuals with MRSA in their natural flora)
• Discharge of patients to nursing homes
• Chronic wounds
• Usage of central venous catheters (CVCs) in hospitalized patients
• Usage of invasive devices
• Hemodialysis 

(Epstein et al., 2016)

 

Diagnosis 

Clinical Features

Different types of MRSA infections have different clinical presentations, and some may even be asymptomatic and thus require further testing for confirmation (Tong et al., 2015).

Community-acquired MRSA infections are typically seen as infections of the skin, presented as bullous impetigo that progresses into large, dried scabs and sometimes skin lesions (Tong et al., 2015). Device-related MRSA infections may also present some inflammatory manifestations on the skin at the site of insertion, but they lead to bacteremia (Sahli et al., 2017).

In more severe infections originating from bacteremia, including infective endocarditis, the infection is often misdiagnosed or not diagnosed at all, as the disease manifestations are non-specific, such as fever and ultimately septic shock (Yang & Frazee, 2018). Urinary catheters further lead to UTIs which are associated with fever (Muder et al., 2006). 

Note that diagnosis must be confirmed with more testing, namely bacterial cultures, to ensure the nature of the pathogen establishing the infection (Tong et al., 2015).

 

Pathological Features

Further testing for the presence of MRSA strains in soft tissue or blood is required in order to confirm diagnosis and further move forward with a treatment plan(Palavecino, 2020).

Testing may be done via FilmArray blood cultures, antibiotic-resistant testing using methicillin discs, and PCR may also be used for sequencing genes that would identify the cultured bacteria as MRSA (Palavecino, 2020).

 

Treatment

Treatment involves the removal of any source of infection, for example, CVCs or urethral catheters, or any other device that has caused the MRSA infection (Hassoun et al., 2017).

Patients with prosthetic valves who have developed MRSA infections must receive valve replacement surgery to eliminate the source of infection (Hassoun et al., 2017). Surgery may also be required for patients with infective endocarditis (Yang & Frazee, 2018).

For treatment of MRSA bacteremia, vancomycin and daptomycin are recommended via intravenous administration, though multidrug regimens and possible synergistic effects of using drugs in combination are currently under investigation to prevent the development of new antibiotic-resistant strains (Lewis et al., 2018).

For skin infections, incision and drainage (I/D) are recommended and may be accompanied by antibiotics such as TMP/SMX, though the effectiveness of I/D over antibiotic treatment has not yet been established, and current clinical trials are investigating the effectiveness of both treatments, monotherapy with Clindamycin, TMP/SMX, or use of I/D methods alone (Creech et al., 2015).

 

Articles on Misdiagnosis

Dominguez, T. J. (2004). It’s Not a Spider Bite, It’s Community-Acquired Methicillin-Resistant Staphylococcus aureus. The Journal of the American Board of Family Medicine, 17(3), 220–226.doi:10.3122/jabfm.17.3.220

T. J. Tsang, M. P. McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh, I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed. Bone Joint Res 2018;7:79–84. DOI: 10.1302/2046-3758.71.BJR-2017-0175.R1.

Glenn Tillotson & Nick van Hise (2020): Screening for Methicillin resistant Staphylococcus aureus (MRSA): a valuable antimicrobial stewardship tool?, Expert Review of Anti- infective Therapy, DOI: 10.1080/14787210.2021.1865800

 

References

 

Creech, C. B., Al-Zubeidi, D. N., & Fritz, S. A. (2015). Prevention of Recurrent Staphylococcal Skin Infections. Infectious Disease Clinics of North America, 29(3), 429–464. https://doi.org/10.1016/j.idc.2015.05.007

Epstein, L., Mu, Y., Belflower, R., Scott, J., Ray, S., Dumyati, G., Felsen, C., Petit, S., Yousey-Hindes, K., Nadle, J., Pasutti, L., Lynfield, R., Warnke, L., Schaffner, W., Leib, K., Kallen, A. J., Fridkin, S. K., & Lessa, F. C. (2016). Risk Factors for Invasive Methicillin-Resistant Staphylococcus aureus Infection After Recent Discharge From an Acute-Care Hospitalization, 2011–2013. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 62(1), 45–52. https://doi.org/10.1093/cid/civ777

Fernando, S. A., Gray, T. J., & Gottlieb, T. (2017). Healthcare-acquired infections: Prevention strategies. Internal Medicine Journal, 47(12), 1341–1351. https://doi.org/10.1111/imj.13642

Hassoun, A., Linden, P. K., & Friedman, B. (2017). Incidence, prevalence, and management of MRSA bacteremia across patient populations—A review of recent developments in MRSA management and treatment. Critical Care, 21. https://doi.org/10.1186/s13054-017-1801-3

Katayama, Y., Ito, T., & Hiramatsu, K. (2000). A New Class of Genetic Element, Staphylococcus Cassette Chromosome mec, Encodes Methicillin Resistance in Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 44(6), 1549–1555.

Krismer, B., Weidenmaier, C., Zipperer, A., & Peschel, A. (2017). The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nature Reviews Microbiology, 15(11), 675–688. https://doi.org/10.1038/nrmicro.2017.104

Lee, A. S., de Lencastre, H., Garau, J., Kluytmans, J., Malhotra-Kumar, S., Peschel, A., & Harbarth, S. (2018). Methicillin-resistant Staphylococcus aureus. Nature Reviews Disease Primers, 4(1), 1–23. https://doi.org/10.1038/nrdp.2018.33

Lewis, P. O., Heil, E. L., Covert, K. L., & Cluck, D. B. (2018). Treatment strategies for persistent methicillin-resistant Staphylococcus aureus bacteraemia. Journal of Clinical Pharmacy and Therapeutics, 43(5), 614–625. https://doi.org/10.1111/jcpt.12743

Muder, R. R., Brennen, C., Rihs, J. D., Wagener, M. M., Obman, A., Obman, A., Stout, J. E., & Yu, V. L. (2006). Isolation of Staphylococcus aureus from the Urinary Tract: Association of Isolation with Symptomatic Urinary Tract Infection and Subsequent Staphylococcal Bacteremia. Clinical Infectious Diseases, 42(1), 46–50. https://doi.org/10.1086/498518

Palavecino, E. L. (2020). Rapid Methods for Detection of MRSA in Clinical Specimens. In Y. Ji (Ed.), Methicillin-Resistant Staphylococcus Aureus (MRSA) Protocols: Cutting-Edge Technologies and Advancements (pp. 29–45). Springer US. https://doi.org/10.1007/978-1-4939-9849-4_2

Sahli, F., Feidjel, R., & Laalaoui, R. (2017). Hemodialysis catheter-related infection: Rates, risk factors and pathogens. Journal of Infection and Public Health, 10(4), 403–408. https://doi.org/10.1016/j.jiph.2016.06.008

Tong, S. Y. C., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler, V. G. (2015). Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management. Clinical Microbiology Reviews, 28(3), 603–661. https://doi.org/10.1128/CMR.00134-14

Yang, E., & Frazee, B. W. (2018). Infective Endocarditis. Emergency Medicine Clinics of North America, 36(4), 645–663. https://doi.org/10.1016/j.emc.2018.06.002