MRSA Skin Infection in Athletes

Staphylococcus aureus is a natural bacterium in human hosts that can also cause a broad spectrum of disease. ^[1] Community-associated skin and soft-tissue infections (SSTIs) are most commonly caused by staphylococci or streptococci. Over the past 4 decades, epidemiologic tendencies have shown an escalation not only in healthcare-associated methicillin-resistant S aureus (HA-MRSA) but also in community-associated MRSA (CA-MRSA). ^[2]

CA-MRSA infections have become more common in athletes ^{[3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15]} and active individuals since the first reported cases in a high school wrestling team in 1993 ^[16] and a British rugby club in 1998. ^[17] CA-MRSA differs from HA-MRSA in its genetic makeup, its increased pathogenicity, and its susceptibility to antibiotic treatment. ^{[18, 19, 20]}

For patient education resources, see Infections Center, MRSA Infection (Methicillin-Resistant Staphylococcus aureus Infection), Sepsis (Blood Infection), Life-Threatening Skin Rashes, and Antibiotics.

In the United States, most community-associated methicillin-resistant S aureus (CA-MRSA) infections have been caused by the USA300 epidemic clone. Outbreaks caused by USA300 have been reported in at least 38 states, and this strain accounts for 50% of all S aureus infections ^[21] and up to 98% of CA-MRSA infections in the United States. ^[22]

The resistance of MRSA to beta-lactam antibiotics is due to the presence of the mecA gene sequence. The mecA gene produces transpeptidase PBP2a (penicillin-binding peptide) that decreases the bacterial affinity for beta-lactam antibiotics. ^{[19, 23, 24]}

The mecA gene is carried as a mobile genetic element in a staphylococcal chromosome cassette (SCC), with the entire complex known as the SCCmec element.

Hospital-associated MRSA (HA-MRSA) typically contains SCCmec genes type II (SCCmecII) and III (SCCmecIII), which are larger genes and confer multidrug resistance. ^[25] The CA-MRSA strains have SCCmec type IV gene (SCCmecIV), a small gene which codes for fewer resistance elements and thus retains susceptibility to macrolides, quinolones, tetracyclines, trimethoprim-sulfamethoxazole, and lincosamides. ^[1]

CA-MRSA has been found in some cases to be more virulent than HA-MRSA. Besides conferring methicillin resistance, the SCCmecIV genes also code for the arginine catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL) virulence factor. ^[21] PVL is a bicomponent toxin that forms pores in neutrophils; it has been associated with furunculosis and severe bone and joint infections. ^[1]

MRSA colonization

According to a US population-based survey, the community prevalence of methicillin-sensitive S aureus (MSSA) was 31.6% and that of methicillin-resistant S aureus (MRSA) WAS 0.84%, with the anterior nares being the most consistent site of isolation. ^[26] Other less common sites of colonization include the skin, perineum, gastrointestinal tract, and throat.

Populations that have been reported to have increased rates of S aureus colonization include persons with type 1 diabetes, intravenous drug users, asthmatic patients, the elderly, persons who require hemodialysis or peritoneal dialysis, persons with rheumatoid arthritis, those with chronic sinusitis, and persons with human immunodeficiency virus (HIV) infection. ^[26]

Socio-economic and lifestyle aspects that predispose to colonization include: overcrowding, poor access to healthcare, suboptimal personal hygiene practices, and sharing of personal items. ^[1] Populations reportedly at risk for CA-MRSA outbreaks specifically include military recruits, children in day care, prison inmates, homosexual men, injection drug users, and veterinarians, particularly those who have contact with swine. ^{[7, 27, 28]}

A study by Jiménez-Truque et al assessed colonization of S. aureus in 377 athletes and trainers and reported prevalence rates of colonization with S. aureus as 34% to 62%  and with MRSA of 8% to 29%. The study also reported a significantly higher colonization rate in the summer than in the winter. ^[29]

CA-MRSA outbreaks in athletes and other populations

Most publicized reports of CA-MRSA infection have been on college or professional football teams. ^{[3, 4, 5, 6, 7, 8]} However, outbreaks have also been reported in other sports, such as wrestling, rugby, and fencing. In a study of all Nebraska high schools between 2006 and 2008, Buss et al determined that among the schools that responded, MRSA infections rose from 4.4% in the 2006-2007 academic year to 14.4% in the 2007-2008 academic year; the incidence per 10,000 wrestlers rose 3-fold from 19.6 to 60.1 and that per 10,000 football players increased 5-fold from 5.0 to 25.1. ^[11]

Skin and soft-tissue infections (SSTIs) represent approximately 90% of all S aureus infections. ^[1] Most community-associated methicillin-resistant S aureus (CA-MRSA) infections initially manifest as folliculitis or similar SSTIs. Classically, the athlete may describe his or her presentation as an "infected pimple" or "insect bite." Some CA-MRSA infections may progress to abscess formation.

The initial clinical examination usually reveals a localized area of erythema, warmth, and swelling. Occasionally, the patient may have swelling and pain in a joint. Alternatively, sports-related CA-MRSA may present as an abscess with surrounding cellulitis in an athletic young adult, with pain that is out of proportion to the findings on physical examination. ^[13] In more advanced cases, moderate to severe pain at the site of the infection may be reported; the pain may result from soft-tissue necrosis from Panton-Valentine leukocidin (PVL) activity.

Although not very prevalent in athletes, invasive disease that causes infections of the bloodstream, respiratory tract, bones, joints, and surgical wounds are concerning due to their associated elevated morbidity and mortality. ^[1] In severe cases of CA-MRSA infection, endocarditis, septicemia, necrotizing fasciitis, osteomyelitis, and multisystem organ failure, or death due to overwhelming sepsis may occur. Mortality from S aureus bacteremia is estimated to be 10-20% in the developed world. ^[30]

Yokomori et al reported a life-threatening case of CA-MRSA USA300 clone infection in a college athlete in Japan. The patient developed septic pulmonary emboli secondary to infectious iliofemoral deep venous thrombosis and abscesses. ^[31]

Transmission

The most common route of transmission of CA-MRSA is though an open wound, such as a superficial abrasion, or from contact with a CA-MRSA carrier. Other methods of transmission include poor hand washing, poor personal hygiene (eg, not showering after workouts), sharing personal items (eg, razors, towels, clothing), or a failure to properly clean and disinfect exercise and training equipment. ^[32]

In 2004, an outbreak of MRSA strain USA300 occurred amongst college football players in Connecticut. ^[9] The infection was associated with player position (cornerbacks and wide receivers), abrasions from artificial grass ("turf burns"), and body shaving (relative risk, 6.1) as the most obvious portal of entry of S aureus. Cornerbacks and wide receivers were a subpopulation with frequent direct person-to-person contact with each other. ^[8]

Outpatient treatment

The primary method of treatment for community-associated methicillin-resistant S aureus (CA-MRSA) skin and soft-tissue infections (SSTIs)) includes incision and drainage (I&D) of abscesses, inflamed epidermoid cysts, carbuncles, and large furuncles. Systemic therapy with anti-staphylococcal antibiotics are indicated in moderate to severe disease, especially in the presence of systemic inflammatory response syndrome (SIRS), as definied by two or more of the following:

• Temperature greater than 38ºC or lower than 36ºC

• Tachypnea (>24 breaths per minute)

• Tachycardia (>90 beats per minute)

• White blood cell (WBC) count greater than 12,000 cells/μL or less than 400 cells/μL

In the presence of purulent discharge, obtain cultures to identify the causative organism and allow for directed antibiotic therapy. ^[33]

Topical antibiotics

Mupirocin and retapamulin are topical antibiotic treatments of choice for bullous and nonbullous impetigo. These agents are used twice daily for 5 days. However, in patients with multiple lesions or in outbreak settings, oral treatment is preferred to help reduce transmission of infection.

Oral antibiotics

Oral (PO) antibiotic agents that may be used to treat to CA-MRSA on an outpatient basis include the following:

• Trimethoprim-sulfamethoxazole (Bactrim DS): Administer 1 or 2 tablets PO twice daily for 7 days ^[33]

• Clindamycin: Administer 300-450 mg PO 3 times a day; resistance to clindamycin is increasing because of the inducible macrolide-lincosamide-streptogramin B (iMLSb) phenotype, which may result in cross-resistance to clindamycin

• Doxycycline: Administer 100 mg PO twice daily; this agent is not recommended for children younger than 8 years

• Linezolid: Administer 600 mg PO twice daily; note that cost often prohibits the use of this agent

Note that ciprofloxacin has a 33% sensitivity in some areas. Therefore, this drug is not recommended due to resistance and reports of clinical failures despite in vitro susceptibility.

The susceptibility of CA-MRSA is dependent on local resistance rates (US Centers for Disease Control and Prevention [CDC] guidelines [see Antibiotic/Antimicrobial Resistance and Healthcare-associated Infections [HAI]).

Inpatient treatment

Treatment of moderate to severe CA-MRSA infections may require surgical debridement of the abscess, intravenous (IV) antibiotics, and hospitalization. The need for hospitalization should be made on a case-by-case basis.

IV antibiotics

IV antibiotics that may be used to treat inpatient cases of CA-MRSA include the following:

• Vancomycin: Administer 30 mg/kg/day IV in two divided doses; vancomycin is the parenteral drug of choice for treatment of infections caused by MRSA

• Linezolid: Administer 600 mg IV every 12 hours; this agent may increase serotonin central nervous system (CNS) levels as a result of MAO-A inhibition, thereby increasing the risk of serotonin syndrome ^[34]

• Clindamycin: Administer 600 mg IV every 8 hours

• Daptomycin: Administer 4 mg/kg IV every 24 hours; note that this agent can cause myopathy

• Ceftaroline: Administer 600 mg IV twice a daily ^[35]

• Dalbavancin: Administer 1 g IV once weekly; this agent is a second-generation bactericidal glycopeptide that received US Food and Drug Administration (FDA) approval in May 2014 for the treatment of S aureus infections (MRSA and methicillin-sensitive S aureus [MSSA]) after it was proven to be noninferior to vancomycin IV and then linezolid PO in the DISCOVER-1 and DISCOVER-2 trials, respectively ^[36]

• Tedizolid: Administer 200 mg IV once daily, infused over 1 hour, for 6 days ^[37] ; this agent is an oxazolidinone antibacterial drug designed to enhance activity against gram-positive pathogens; tedizolid received FDA approval in June 2014 for the treatment of MRSA and MSSA SSTIs after it was proven to be statistically noninferior to linezolid in the ESTABLISH-1 and ESTABLISH-2 trials ^{[38, 39]}

Recurrent infections

When an athlete has recurrent MRSA infections, clinicians should suspect resistance to the previous antibiotic or nasal colonization. Obtain a nasal swab for culture to determine if decolonization is necessary. Recurrent abscesses need to be drained and cultured early in the course of the infection, followed by administration of a 5-10 – day course of targeted antimicrobial therapy. If the nasal swab culture is positive for CA-MRSA, the athlete should complete a 5-day regimen of with mupirocin antibiotic ointment twice a day applied to the nares and chlorhexidine washes once daily, in conjunction with daily decontamination of personal hygiene items (eg, towels) in an effort to decolonize the individual and to reduce the likelihood of recurrence. ^[33]

Several key methods can be used for prevention of the spread of community-associated methicillin-resistant S aureus (CA-MRSA) infections. ^[40] Because the most common source of infection is from close contact or from an open wound, preventive measures should focus on proper hygiene. Hand washing, using liquid soap instead of bar soap in institutions (to prevent sharing of a contaminated surface), and antibacterial hand gels should be encouraged, both for the infected patient as well as for individuals who come in direct contact with the patient. Additionally, open wounds and abrasions should be covered and protected.

Athletes should be educated and instructed to not share personal hygiene products such as razors or towels. Cleaning and disinfection are important for items such as mats, stretchers, locker room benches, and floors.

Medical and training staff should continue to practice universal infectious disease protection measures. These personnel should ensure the proper disposal of bandages after dressing changes and the routine cleaning of equipment such as training tables, whirlpools, and exercise mats. Additionally, athletic trainers must be familiar with the most evidence-based guidelines for infection control in the athletic facility and apply those recommendations accordingly. ^[41]

Nonantibiotic methods to reduce nasal colonization by S aureus are emerging. A study by Steed et al showed nasal application of a nonantibiotic, alcohol-based antiseptic (Nozin Nasal Sanitizer Advanced Antiseptic from Global Life Technologies, Corp) was effective in reducing S aureus and total bacterial carriage, suggesting the usefulness of this approach as a safe, effective, and convenient alternative to antibiotic treatment. Seventy-eight of 387 healthcare providers screened (20.2%) tested positive for S aureus infection. Of 39 subjects who tested positive for S aureus infection who completed the study, 20 received antiseptic and 19 received placebo treatment. Antiseptic treatment reduced S aureus colony forming units from baseline by 99% (median) and 82% (mean) (P < 0.001). Total bacterial colony forming units were reduced by 91% (median) and 71% (mean) (P < 0.001). ^[42]

Athletes with mild cases of community-associated methicillin-resistant S aureus (CA-MRSA) infections should be removed from team-related activities until 72 hours after initiation of oral antimicrobial therapy and demonstrated clinical improvement (ie, the presence of a well-formed scab without active discharge). ^[43] Abrasions, infected or not, should be covered with a protective covering, and the athlete should be reevaluated daily for signs or symptoms of recurrence or worsening of the infection. Training staff should ensure proper disinfection of equipment and surfaces with which the infected athlete may come in contact, such as training tables, protective equipment, or wrestling mats, among other items.