Community-Acquired Methicillin-Resistant Staphylococcus aureus Infection in Community-Dwelling Older Adults: Is It a Problem and What Should You Do?

Case Vignette

Mr. N was a 65-year-old man who presented to the emergency department with an abscess of the left elbow of 1-week duration; he was otherwise healthy. He had required internal fixation for a tibial fracture 3 months earlier, and the incision healed well without complication. His abscess was incised, and cultures grew numerous Staphylococcus aureus that were resistant to all beta-lactam antibiotics. This methicillin-resistant S. aureus (MRSA) isolate was otherwise susceptible to all other antibiotic classes, including macrolides, lincosamides, and aminoglycosides. Mr. N was treated for 2 days with intravenous vancomycin 1500 mg every 24 hours followed by oral trimethoprim-sulfamethoxazole (TMP-SMZ) 1 double-strength tablet twice daily for 2 weeks, and the infection resolved.

Several months later, the patient presented to an outpatient clinic with an infected paronychia of the right second finger. The abscess was incised, and cultures again grew MRSA with the same antimicrobial susceptibility pattern that was recorded at his last presentation. A culture of the anterior nares also yielded MRSA, but cultures of the throat, perineal skin, and rectum were negative for MRSA.

The patient recalled that his wife, who had a history of diabetes mellitus, had recently been treated twice for community-acquired MRSA infection. Mrs. N’s physical examination revealed wounds at the base of her neck that were consistent with healing carbuncles and hyperkeratotic plaques involving her elbows, intertriginous areas, and abdomen that were consistent with psoriasis. Her skin and nares were also positive for MRSA, with the same antimicrobial susceptibility pattern as Mr. N’s bacteria.

Mr. N was again treated with the same TMP-SMZ regimen, and he was given topical mupirocin ointment to apply to his anterior nares twice daily for 5 days. He was also advised to use chlorhexidine body washes in the shower once weekly for 1 month. His wife’s physician was contacted as well, and aggressive treatment for her psoriasis and treatment with mupirocin and chlorhexidine for her MRSA infection were advised. Both Mr. and Mrs. N were advised to practice good hygiene, wear clean clothing, avoid sharing linens and towels, and launder these items frequently. Mr. N has had no further recurrences after 1 year of follow-up.

How Has the Epidemiology of MRSA Changed?

Until very recently, MRSA infection was almost exclusively associated with acquisition from hospitals, nursing facilities, dialysis units, and other skilled healthcare settings, and it was referred to as healthcare-associated MRSA (HA-MRSA). Patients with MRSA infection who were admitted to the hospital or other facility from the community generally had some epidemiological link to healthcare settings, whether through a recent admission, contact through dialysis or infusion centers, or from exposure to a family member who had been a patient or worked in the healthcare industry. Other MRSA infections were associated with intravenous drug use in some communities; however, those community-associated MRSA strains were still closely linked to healthcare-associated strains, as demonstrated by their antimicrobial susceptibilities and molecular typing methods.^1,2

In the late 1990s, true community-acquired MRSA (CA-MRSA) was found among clusters of severe and fatal MRSA infections described in healthy children who had no identifiable links to a healthcare setting.^1,2 Subsequently, many reports of CA-MRSA in otherwise healthy persons rapidly emerged worldwide. Outbreaks of skin and soft-tissue infections (SSTIs) and necrotizing pneumonia predominated among young healthy people, persons in the military, athletes, native peoples, and prison populations. In addition to spread from person to person, acquisition of CA-MRSA was frequently associated with exposure to contaminated fomites or the environment.^1,2

Where Did CA-MRSA Come From?

All MRSA are characterized by the presence of altered proteins on their cell walls, termed penicillin-binding protein 2A (PBP2a). It is PBP2a’s low affinity for antistaphylococcal penicillins that renders MRSA resistant to all beta-lactam antibiotics. There is evidence that the gene mecA, which encodes PBP2a, probably originated in normal skin flora such as coagulase-negative staphylococci and was transferred to methicillin-susceptible S. aureus (MSSA) strains via a resistance element termed staphylococcal chromosomal cassette mec (SCCmec).³

There are at least 5 types of SCCmec now identified in MRSA. HA-MRSA has been associated with SCCmec types I through III. In contrast, CA-MRSA has been characterized by the presence of SCCmec type IV and SCCmec type V, confirming that these strains arose anew and did not originate in the healthcare setting.^2-4

HA-MRSA strains typically harbor resistance elements for numerous antibiotic classes, including macrolides, lincosamides, aminoglycosides, fluoroquinolones, tetracyclines, and sulfonamides. In contrast, CA-MRSA strains contain fewer resistance genes and generally are more susceptible to many classes of antibiotics, although multidrug-resistant strains are beginning to emerge.⁵

The smaller cassette found in CA-MRSA also seems to confer a survival advantage over the big, bulky HA-MRSA cassette. Why were HA-MRSA strains generally restricted to the healthcare setting? One hypothesis is that the extra genetic “baggage” found in HA-MRSA may have actually limited its ability to grow. In healthcare environments, increased antibiotic use likely suppressed more susceptible normal flora and allowed HA-MRSA to thrive.^3,6 In contrast, CA-MRSA grows quite readily, even with antibiotic use and when there is low antibiotic selective pressure.^6,7

As patients with CA-MRSA are admitted to healthcare facilities, will these strains be able to compete with HA-MRSA for dominance in healthcare facilities? Specific genotypes of CA-MRSA, such as USA300 and USA400, have already become significant pathogens in many healthcare centers.^2,8,9 Furthermore, patients could bring CA-MRSA home to infect family members^10,11; in fact, clusters of CA-MRSA infections have been detected in members of households in several studies.^12,13 It appears that distinguishing strains just on the basis of place of acquisition may no longer be valid.⁹

What Is the Impact of CA-MRSA?

Studies from around the world have shown that SSTIs and S. aureus infections are increasing.^14-16 A study published in 2009 reported that admissions to hospitals due to SSTI increased by 29%, from 675,000 in 2000 to 869,800 in 2004.¹⁴ The rates of ambulatory care visits for staphylococcal SSTI have also increased: when 2001-2003 data were compared with 1992-1994 rates, outpatient and emergency department visits rose by 59% and 31%, respectively.¹⁵ The vast rise in admissions and ambulatory care visits for SSTI have primarily been ascribed to increases in superficial infections, such as abscesses and cellulitis, rather than deep-tissue infections or infections related to surgical procedures or devices.^14,16

Increased hospitalizations and healthcare visits due to SSTI clearly correlate with the emergence of CA-MRSA. In a study that examined data from the National Inpatient Sample from the 2000-2004 U.S. Healthcare Cost and Utilization Project, it was found that, nationwide, CA-MRSA accounted for 59% of SSTI and 14% of invasive infections among patients seen in emergency departments.¹⁴ CA-MRSA is now reported as a major cause of SSTI by many major medical centers, with ambulatory infection rates ranging from 45% to 75%.¹⁶

A study by Davis et al¹² found that most patients with CA-MRSA and CA-MSSA presented with SSTI (80% and 93%, respectively), followed less commonly by respiratory tract infection (13% and 6%, respectively) and bacteremia (4% and 1%, respectively). Most CA-MRSA SSTIs will be localized and relatively superficial due to abscesses (50%-75%), and 25% to 50% of cases will present with cellulitis rather than deeper infections.¹⁷

Is CA-MRSA a Problem in Older Adults?

In contrast with HA-MRSA, most CA-MRSA infections occur in younger persons than in older adults.^4,18,19 In addition, Edelsberg et al¹⁴ reported that more cases of superficial SSTI attributed to the emergence of CA-MRSA are diagnosed in persons under 65 years of age as compared with older persons (37% vs 14%, respectively). A review of 12 reports of CA-MRSA pneumonia confirmed that most patients with this infection are younger (median patient age ranged from 7 months to 42 years) as compared with healthcare-associated staphylococcal pneumonia, a diagnosis that is primarily found in debilitated older adults.^6,20

The increased morbidity and mortality seen with CA-MRSA in the young is potentially related to the ability of these strains to produce toxins. The genes that encode Panton-Valentine leukocidin (PVL) have been found in most CA-MRSA lineages, including USA300 strains, but the expression of those genes and the production of the toxin may be variable. Staphylococcal enterotoxins and other virulence factors may also be responsible for causing disease.^3,7,17,20

In a study from Australia, older patients seemed to be infected with PVL-producing strains of CA-MRSA less often than younger persons.¹⁹ Some investigators have suggested that older adults may be less likely to have infection with CA-MRSA or PVL-positive strains because antibodies to antistaphylococcal toxins increase with age.²¹ Healthy older adults age 50 years and older are known to have protective antibodies to toxic shock syndrome toxin-1 and staphylococcal enterotoxins more often than younger adults, and thus have lower rates of toxic shock syndrome.²² Whether debilitated older patients in healthcare facilities will be protected from CA-MRSA infection is not clear, particularly if they have other traditional risk factors for MRSA.

When Should Healthcare Providers Suspect CA-MRSA in Older Adults?

Toxins that destroy neutrophils and lead to unimpeded tissue destruction and necrosis may explain the characteristic features of CA-MRSA infection. Fever and leukocytosis may be absent, and symptoms of pain and tenderness may be prominent and out of proportion with clinical findings. Central tissue necrosis surrounded by erythema in association with large inflammatory subcutaneous masses are the dominant clinical findings rather than pus.^2,17,21 Recurrence of these “abscesses” is frequent. Many of these CA-MRSA SSTIs are initially misdiagnosed as brown recluse spider bites; this diagnosis is extremely unlikely outside of the spider’s endemic territory in Missouri, Oklahoma, Arkansas, Louisiana, and surrounding areas.²¹

Other severe necrotizing infections, involving the fascia, muscles, lungs, and pleural spaces, have been described in association with bacteremia, sepsis syndrome, and purpura fulminans. CA-MRSA pneumonia may be seen after influenza infection; hemoptysis may be a prominent finding of CA-MRSA.^6,20

How Is CA-MRSA Diagnosed?

The diagnosis of CA-MRSA should be considered in the older patient who presents with possible staphylococcal infection, especially if treatment with empiric antistaphylococcal beta-lactam antibiotics was not effective, and even if traditional risk factors for HA-MRSA are absent. Suspicion that MRSA infection might be a possibility in the community-dwelling older person is an essential first step in the diagnosis and appropriate treatment of CA-MRSA. Obtaining clinically relevant specimens for culture is essential in patients in whom MRSA infection is suspected. For the majority of patients who are otherwise healthy and present with a single abscess, as was the case with Mr. N, incision and drainage to obtain pus or deep tissue for culture may be sufficient.

When systemic signs and symptoms of infection are present, blood cultures should be obtained. All patients with bacteremia should be carefully assessed for the presence of endocarditis, empyema, abscesses, and other metastatic complications of CA-MRSA infection.² In patients with respiratory symptoms, sputum cultures and a chest roentgenograph should be obtained as part of an evaluation for pneumonia.⁶ Computed tomography can be helpful in the evaluation of suspected fasciitis, myositis, or empyema.

Molecular methods used to detect SCCmec type IV and SCCmec type V in CA-MRSA strains are not available in clinical microbiology laboratories. CA-MRSA strains are significantly more likely than HA-MRSA isolates to be susceptible to gentamicin (94% vs 80%, respectively), clindamycin (83% vs 21%, respectively), ciprofloxacin (79% vs 16%, respectively), and erythromycin (44% vs 9%, respectively).⁶ However, it is anticipated that the antibiogram will be less useful to differentiate HA-MRSA from CA-MRSA strains, as the latter become part of normal hospital flora and acquire resistance genes to other antibiotics.⁶

What Are the Treatment Options for CA-MRSA?

Prompt incision and drainage of CA-MRSA infection is the mainstay of treatment, especially when the patient is critically ill. For abscesses, drainage may be the only treatment that is necessary.^17,23,24 Whether antibiotics are beneficial for the treatment of small abscesses remains controversial.¹⁷ Some experts do not recommend antibiotic treatment if the abscess is small (<5 cm) and the patient has no systemic signs of fever, tachycardia, or hemodynamic instability.^2,17 In patients with systemic symptoms, severe infection, abscesses involving the head and neck, or large abscesses, treatment with systemic antibiotics would be appropriate in addition to the aggressive drainage of pus and the debridement of necrotic tissue.^2,17

Empiric antibiotic choices for possible CA-MRSA infection should be based on the severity of the infection, the likelihood of antibiotic susceptibility, and the site of the infection. For antibiotic treatment of a localized abscess, oral TMP-SMZ, clindamycin, and doxycycline are readily available at low cost. Unfortunately, no randomized controlled trials have yet been conducted to ascertain which antibiotic is most efficacious for the treatment of CA-MRSA infection.

For cellulitis alone, without evidence of an abscess or fluctuance, group A streptococci are more likely to be the cause of infection than CA-MRSA. When cellulitis with possible abscess is present, and either group A streptococci or CA-MRSA is suspected, clindamycin is the preferred empiric treatment, as little is known about group A streptococci’s resistance to tetracyclines or sulfonamides.² 

For the empiric treatment of large abscesses, infections with fever or other manifestations of systemic illness, or high-risk patients with diabetes or immunodeficiency, intravenous vancomycin and daptomycin, as well as oral or intravenous linezolid, have been recommended. For the treatment of severe MRSA infection, the greatest therapeutic experience has been found with the use of vancomycin, but treatment failures coupled with rising minimum inhibitory concentrations have occurred, prompting a search for better drugs.⁶ Like vancomycin, daptomycin is also a bactericidal drug; it has been approved for the treatment of SSTI, bacteremia, and endocarditis. Daptomycin is not recommended for treatment of pneumonia because lung surfactant inhibits drug activity and drug levels are low. Linezolid and tigecycline are bacteriostatic agents. Linezolid has been used for the treatment of MRSA SSTI, pneumonia, and secondary bacteremia, but is not recommended for the routine treatment of endocarditis. Tigecycline has also been approved for the treatment of complicated SSTI. Unfortunately, there is no perfect agent for every situation. Each of these drugs has its own unique side-effect profile, and resistance has been reported.^2,17,21 It is prudent to confirm the susceptibility of CA-MRSA isolates by testing them in a clinical microbiology laboratory. CA-MRSA isolates may appear to be susceptible on routine antibiotic testing when, in fact, they are resistant to one or more classes of antibiotics. CA-MRSA strains may be resistant to antibiotics through several mechanisms, including inducible resistance and heteroresistance.

With inducible resistance, CA-MRSA can be resistant to macrolides, lincosamides, streptogramins, or tetracyclines, but the isolate appears to be susceptible to a drug from these classes on initial testing. A resistance gene can be turned on or induced in the presence of that antibiotic, leading to the development of resistance during therapy. Fortunately, most clinical microbiology laboratories can perform a simple D test to see if inducible resistance to clindamycin is present. The D test involves placing an erythromycin disc in close proximity to a clindamycin disc on an agar plate that is inoculated with CA-MRSA. If erythromycin-inducible clindamycin resistance is present, the circular zone of inhibition surrounding the clindamycin disc will be flattened or inhibited where it interacts with the zone surrounding the erythromycin disc. This “D-shaped” zone of inhibition around the clindamycin disc, or positive D test, means that resistance to clindamycin, inducible by erythromycin, is present and that clindamycin should not be used for treatment.^2,17

In the past, resistance to macrolides such as erythromycin automatically implied that lincosamides such as clindamycin should not be used for the treatment of HA-MRSA even if they appeared to be susceptible because cross-resistance was likely. However, it is now known that erythromycin resistance in CA-MRSA can also be mediated by another mechanism that does not confer cross-resistance to clindamycin.⁶

CA-MRSA strains may also have heteroresistance to fluoroquinolones. Heteroresistance means that the majority of bacteria within a CA-MRSA isolate are susceptible to fluoroquinolones, but some bacterial clones are present with varying degrees of resistance. Quinolone treatment can quickly eradicate the susceptible bacteria, but the remaining resistant bacteria may survive and resistance can develop on treatment. Unfortunately, routine testing for heteroresistance in MRSA is not feasible for most clinical microbiology laboratories; therefore, it is recommended that fluoroquinolones not be routinely used for the treatment of CA-MRSA, as rapid selection of resistant strains is likely to occur.^2,6

How Can CA-MRSA Be Prevented?

Patients who are infected with CA-MRSA can help prevent the spread to others by covering their wounds with a clean dry bandage, using good hand hygiene after contact with the wound, bathing regularly using regular soap, laundering their clothing, and avoiding sharing personal items such as towels, bedding, clothing, or razors.^2,21 Whether the carriage of CA-MRSA will persist in these patients long-term is unknown. The use of mupirocin ointment in nares with or without chlorhexidine gluconate body washes, or oral combinations of a systemic antibiotic with rifampin have been used to reduce colonization and transmission in healthcare settings, but the prevention of recurrent infection has not been proven. Decolonization may be attempted if multiple recurrences occur or if transmission occurs in a closed setting such as a household.^2,17,21

Summary

The epidemiology of MRSA infection as we have known it is changing. While CA-MRSA is thought to be primarily a disease of younger people, it may cause infections in older adults. The case vignette illustrates the following key points:

•It is important to consider the diagnosis of CA-MRSA even when confronted with a typical staphylococcal SSTI, especially if the patient has not responded to conventional treatment with a beta-lactam antibiotic, and even if the patient does not have traditional risk factors for MRSA.
•Prompt surgical drainage and debridement are the cornerstones of treatment for CA-MRSA infections.
•Culture must be obtained to verify that the infection is due to MRSA and that the organism is susceptible to the antibiotics chosen.
•Recurrent CA-MRSA infection is common and transmission within households can occur.
•Good hygiene is essential to prevent the transmission of CA-MRSA infection.
•Decolonization procedures have not been proven to prevent further infection, but they may be tried when the patient has had recurrent infection and transmission has occurred within a household.

The healthy, community-dwelling case patient likely acquired his recurrent CA-MRSA abscesses from his wife, who had had recurrent abscesses with CA-MRSA. Both spouses were found to be CA-MRSA carriers and the antibiograms of their isolates were identical, suggesting that transmission had occurred. Multiple interventions were implemented at the same time to try to prevent further transmission and reinfection with CA-MRSA. The couple received treatment for their carrier state with mupirocin and chlorhexidine body washes, even though there is no definitive evidence that these decolonization strategies are effective in preventing recurrent infection. Mrs. N also received aggressive treatment of her psoriatic skin disease, a well-known predisposing condition for staphylococcal carriage and infection. Mr. N had no further infections.

The author reports no relevant financial relationships.

Dr. Bradley is Professor of Internal Medicine, Department of Internal Medicine, Divisions of Infectious Diseases and Geriatric Medicine, University of Michigan Medical School, and Staff Physician, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.

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