Methicillin-Resistant Staphylococcus Infections
Methicillin-resistant Staphylococcus aureus (MRSA) infection is currently the most common skin infection identified in human emergency rooms, and methicillin resistance is increasing in veterinary medicine.
Staphylococci are gram-positive bacterial organisms which colonize the skin of humans and animals. They are considered a "normal" constituent of the epithelial flora, and are not typically invasive or disease-inducing.
In some cases, however, Staphlococci can cause pathologic infection (disease) which can result in tissue inflammation and/or erosion.
The Evolution of MRSA Infections
Before the development of penicillin, Staphylococcus infections were associated with high morbidity and mortality (Chambers, 2005). Penicillin first became widely used as a front-line therapy for Staphylococcus aureus infections during World War II. Penicillin is a β-lactam antibiotic that acts by binding to transpeptidase, which is involved in cell wall peptidoglycan synthesis. By binding to transpeptidase, Penicillin disrupts the formation of bacterial cell walls thereby causing cell death (Kirby, 1944). However, within 10 years of its introduction, penicillin began to wane in effectiveness due to bacterial acquisition of plasmid-encoded β-lactamase, an enzyme that inactivates the lactam ring of β-lactam antibiotics.
Methicillin was subsequently implemented as a means to counteract β-lactamase resistance. Unfortunately, methicillin-resistant strain of Staph aureus (referred to as MRSA) was identified within just 2 years after methicillin was introduced (Cosgrove, et.al, 2003).
Methicillin-resistant Staphylococcus (MRS) infections are caused by Staphylococcus spp that are resistant to all currently available β-lactam antimicrobials and carbepenems (Crawford, et.al, 2006). MRS species have acquired a mobile genetic element known as the staphylococcal cassette chromosome (SCC). The SCC carries a gene (the mecA gene) that encodes for the production of an altered penicillin-binding protein (PBP2a) (Utsui, et.al, 1985). This protein is able to perform all of the required cellular functions but does not allow binding of β-lactam antimicrobials. The SCC also contains insertion sequences that allow incorporation of additional antimicrobial resistance markers. These insertion sequences are why many MRS are resistant to non-β-lactam antimicrobials that act through mechanisms other than interference with bacterial cell wall synthesis.
Both methicillin-susceptible Staphylococcus (MSS) and MRS species can cause serious infection, although there is greater concern with regard to MRS infection due to lack of available treatment options.
MRSA in Horses
MRSA infections were identified in horses in the 1970s (Shimizu, et.al, 1997). Staphylococcus pseudintermedius (formerly misclassified as Staphylococcus intermedius) is the Staphylococcus species most commonly isolated from animals. It has been speculated that the true prevalence of S. pseudintermedius infection in veterinary medicine may be higher than that documented in the literature because these isolates are easily missed by routine disk diffusion and broth microdilution methods (Gortel, et.al, 1999).
Diagnosis of Methicillin Resistance
Diagnosis of methicillin resistance involves bacterial culture and susceptibility testing of appropriate specimens. Special transport media are not required, and refrigerated samples survive well during routine transport. Oxacillin is used for in vitro testing because the disks have greater stability and the test results correlate better with the methicillin resistance of S. aureus isolates from people (Kania, et.al, 2004).
Other tests that can be used include polymerase chain reaction (PCR) assay for the detection of the mecA gene and a latex particle agglutination test that detects the PBP2a antigen. Molecular detection of the mecA gene using PCR is considered the gold standard for making a definitive diagnosis of methicillin resistance in humans. However, veterinary studies have shown a poor correlation between the presence of the mecA gene and PBP2a antigen and methicillin resistance in Staphylococcus spp. (Kania, et.al, 2004).
In human medicine, suspicion for MRSA is heightened by a history of previous MRSA infection or contact with a colonized individual. However, many human patients have no apparent risk factors. In addition, there are no clinical features that distinguish with certainty skin and soft tissue infections caused by MRSA from those caused by methicillin-susceptible S. aureus in people (Miller, et. al, 2007). Comparison studies of lesion appearance between MRSA and methicillin-susceptible S. aureus infections in veterinary species have not been reported.
Treatment of MRSA Infections
Treatment of MRSA infections in humans depends on the severity of the clinical presentation and the type of skin and soft tissue infection. Purulent skin and soft tissue infections without associated systemic signs, such as fever, tachycardia, or hemodynamic instability, are generally managed with incision and drainage with or without oral antimicrobial therapy. However, the optimal treatment strategy is still intensely debated in human medicine (Gorwitz, et.al, 2011).
Tetracyclines and trimethoprim-sulfamethoxazole (TMS) are not recommended as sole empirical therapy for nonpurulent cellulitis because of concerns regarding resistance of group A streptococci to these agents (Swartz, 2004). However, these antimicrobials are reasonable choices in cases of confirmed MRSA. Doxycycline and minocycline appear effective in the treatment of skin and soft tissue infections caused by MRSA and have greater antistaphylococcal activity than tetracycline. A retrospective review of skin and soft tissue infections caused by MRSA in people reported a cure rate of 83% for treatment with doxycycline (Ruhe, et.al, 2005).
Sulfa drugs are reportedly active against 90-100% of community-acquired MRSA (CA-MRSA) isolates in people. However, efficacy data associated with these reports appear to be inconsistent (Proctor, 2008). For example, in a study at a human outpatient clinic in Boston, the percentage of patients with clinical resolution of MRSA infections increased in parallel with Trimethoprim Sulfadiazine use (Szumowski, et.al, 2007). Another study reported treatment failure in 50% of patients who received double-strength TMS (Markowitz, et.al, 1992).
Despite the potential severity of MRSA infections, successful treatment is possible in veterinary medicine. Unfortunately, large-outcome studies for evaluation of veterinary MRS treatment are lacking. As MRSA infections become more common, it will become increasingly important to emphasize submission of diagnostic samples before initiation of empirical antimicrobial therapy. Empirical therapy for wound and incisional infections frequently involves use of β-lactam antimicrobials, which would be ineffective against MRSA.
Public Health Significance
Reports in human medicine suggest that animals may serve as reservoirs for human MRSA infection (Cefai, et.al, 1994). The resistance patterns and genetic makeup of MRSA isolates from dogs and cats are generally indistinguishable from those of the most prevalent MRSA strains in the human population (O'Mahony, et.al, 2005). Although this suggests interspecies transmission, it does not indicate the direction of transmission. It is generally assumed that animals become colonized through contact with colonized or infected humans and serve as a source of reinfection or recolonization. This is important when examining pets owned by health care workers, as it is unknown whether ownership by a health care worker increases a pet’s risk of MRSA colonization (Boost, et.al 2010).
MRSA decolonization involves using antimicrobials or antiseptics to eliminate or reduce infectious burden. A study quantified the effect of chlorhexidine bathing and intranasal mupirocin therapy for decolonization of MRSA-colonized human patients in a 16-bed medical coronary intensive care unit (Ridenour, et.al, 2007). Compared with a baseline period during which all MRSA cases were identified through active surveillance, intervention was associated with a 48% decrease in MRSA colonization and infection.
Active screening and strict implementation of infection control protocols in two equine facilities resulted in a rapid reduction in the number of colonized horses and eradication of MRSA colonization on one farm (Kramer, et.al 2006).
Prevention of MRSA Transmission
Studies in human medicine have found that institution of MRSA prevention practices among health care workers can decrease the rate of MRSA transmission in individual facilities as well as across a large population of people. The most critical step for reduction in MRSA transmission is hand hygiene. In veterinary practice, this means that caretakers should wash their hands thoroughly after handling any animal and between handling different animals. Specific means of hand hygiene have been described, although the use of alcohol-based hand rubs has been shown to reduce MRSA rates and is the standard of care recommended by the Centers for Disease Control and Prevention.
Inanimate surfaces (such as counter tops), another potential source of MRSA, should be disinfected regularly to avoid human contamination and transmission.