Methicillin-Resistant Staphylococcal Infections

This article was previously published in an earlier issue of Clinician's Brief. It has been updated and modified for present use.

Staphylococcus species are part of the normal mammalian and avian flora, but the worldwide increase in methicillin-resistant infections is likely a reflection of increased antibiotic use.

PROFILE

Definition 

• Staphylococcus bacteria (gram-positive, facultative, aerobic cocci) are opportunistic pathogens that can cause skin, body cavity, and soft-tissue infections when inflammation is present and/or the host has compromised defense mechanisms.

• S pseudintermedius, S schleiferi (both coagulase-positive and -negative variants), and, to a lesser extent, S aureus are important organisms in veterinary medicine. 

  • Molecular testing has determined that the primary pathogen of dogs is S pseudintermedius; previous S intermedius isolates are now believed to have been S pseudintermedius. 

• The occurrence of methicillin-resistant staphylococcal infections is increasing.

  • Methicillin resistance is encoded by the mecA gene, which confers intrinsic resistance to all β-lactam antibiotics (ie, penicillins, cephalosporins).

  • The gene is located on the staphylococcal chromosomal cassette along with other resistance genes. This allows resistance to multiple antimicrobials.

• In humans, methicillin-resistant S aureus (MRSA) can be hospital- or community-ac­quired. 

  • Human or animal S aureus carriers without clinical signs are classified as colonized. 

• Studies have shown that up to 30% of humans have nasal colonization of S aureus; approxi­mately 0.5% of those isolates are MRSA.^1,2

Systems

• Skin, soft tissue, and the ears are the most common sites of methicillin-resistant infec­tion; however, any organ has the potential for infection.

Geographic Distribution

• Methicillin resistance has been noted world­wide in humans and animals, but prevalence of MRSA and methicillin-resistant S pseudinter­medius (MRSP) varies widely with geographic distribution.

  • MRSP can be found in or on clinically healthy dogs and cats. Reported prevalence of colonization ranged from 1.5% to 17% in healthy dogs and in healthy cats was 1.2%.³

Signalment

• Methicillin resistance can occur in dogs and cats of any age, breed, or sex.

Transmission & Risk Factors

• Pets are most likely to contract S aureus or MRSA from humans. 

• Studies have shown that <4% of healthy dogs and cats are colonized with MRSA.

• Risk factors for MRSA in pets include infections related to surgery, hospitalization, prior antibiotic use, or exposure to humans with MRSA. Therapy pets in hospital visitation pro­grams are also at increased risk. 

• Pets can acquire MRSP via animal-to-animal contact where healthy colonized pets are the likely source. Receiving recent (within the last year) systemic antimicrobial therapy has also been shown to be a risk factor for acquisition of methicillin-resistant staphylococcal species. Systemic therapy may alter a patient’s commensal staphylococcal flora and allow drug-resistant strains to colonize.

Signs

• Clinical signs of methicillin-resistant infections are identical to methicillin-sensitive infec­tions. Clinical suspicion of methicillin resistance includes lack of response to appropriate empiric therapy, worsening of signs while receiving therapy, and/or recurrent infections (par­ticularly of the skin and ears).

DIAGNOSIS*

Definitive 

• Speciation of S pseudintermedius, S intermedius, and S delphini requires molecular testing; for simplification purposes, isolates from these species are typically referred to as S pseudin­termedius. 

• S schleiferi and S aureus can be identified by standard laboratory speciation test kits.

• Methicillin resistance requires culture and susceptibility testing via broth or agar-based tests.⁴

• Accurate detection of methicillin resistance can be difficult because of heteroresistance (ie, the presence of 2 subpopulations [1 susceptible, the other resistant] that can coexist within a culture). 

  • These cells grow more slowly than oxacillin-susceptible populations and longer incubation periods are required to avoid missing the diagnosis.⁵

• PCR assay is considered the gold standard for detection of the mecA gene.

Other Diagnostics

• Many methicillin-resistant staphylococcal infections in dogs and cats are complicated by secondary yeast overgrowth; cytologic examination of glass microscope slides or clear ac­etate tape is useful to identify organisms.

TREATMENT

Inpatient/Outpatient

• Inpatient care is indicated only if the animal requires surgery, surgical debridement, or sup­portive care because of organ involvement.

Medical

• All MRSP/MRSA infections are resistant to β-lactam antibiotics; some strains may be re­sistant to other antibiotics.

• Systemic antibiotic selection must be based on culture and susceptibility testing. Length of treatment will depend on severity of infection but is usually no less than 21 to 30 days.

• Topical and local therapy (antibacterial sham­poos; ointments; leave-on solution; sprays, lo­tions, or wipes; flushing of abscesses) may be beneficial. This is an underused tool and can be performed in conjunction with appro­priate systemic antimicrobrial therapy. Topical therapy can also help prevent recurrence of in­fection once systemic therapy is complete.  

• Secondary yeast infections should be treated appropriately.

• Grooming and clipping hair from affected areas is crucial in long- or heavy-coated pa­tients.

• Decolonization of healthy animals with MRSA is not necessary and is not recom­mended for healthy animals with MRSP or methicillin-resistant S schleiferi (MRSS). The optimal strategy and efficacy of decolonization practices have not been well-established or well-documented in veterinary medicine. Staphylo­coccal colonization is widespread over the en­tire skin and mucosal surfaces so targeted decolonization is difficult.  

• Careful search for the underlying trigger is critical, particularly when the patient history includes use of multiple antibiotics and/or chronic skin or ear disease.

Activity

• Limiting activity is not indicated unless the infected area requires immobilization or band­aging.

• Infected or colonized dogs should be exercised where they will not encounter other dogs.

• Infected or colonized cats should be kept in­doors.

MEDICATIONS

Topical Therapy 

• Therapy with benzoyl peroxide or chlorhexidine shampoo q24h to q48h is helpful as adjuvant therapy in pets receiving systemic antibiotics.

• Multidrug-resistant staphylococcal infections require intensive daily bathing. It is recom­mended to use 4% chlorhexidine gluconate or chlorhexidine gluconate with tris-EDTA. Medicated bathing is different from a normal grooming bath. Using lukewarm water is preferred so as not to irritate inflamed skin. A minimum contact time of 10 minutes with the shampoo on the skin is ideal for tar­geting surface bacteria. This should be followed by a thorough rinse.

• Mupirocin ointment can be used on focal areas of infection.

Systemic Antibiotics

• Selection of an antimicrobial agent is based on culture and susceptibility testing.

• Use of vancomycin and linezolid in veterinary patients is controversial because of ethical concerns; these drugs are reserved for treat­ment of MRSA in humans.

• Adverse reactions to potentiated sulfonamides (30 mg/kg PO q12h) and chloramphenicol (50 mg/kg PO q8h) can occur. Clients should be warned of idiosyncratic bone marrow sup­pression, which rarely occurs with chloram­phenicol use in humans.⁶

FOLLOW-UP

Patient Monitoring

• Resolution of the infection is monitored by clinical response. Treatment needs to continue beyond resolution of clinical signs. For superfi­cial infections, treatment is recommended for 1 week past clinical resolution; for deeper in­fections, treatment for 2 weeks past clinical resolution is best.

• After resolution of signs, repeat culture is not recommended. Persistence of MRSP on car­riage sites is common following resolution of the infection (eg, pyoderma).

Complications

• Patients receiving potentiated sulfonamide an­tibiotics optimally should have tear production monitored before treatment is initiated and during treatment if keratoconjunctivitis sicca is suspected. 

• Chloramphenicol can cause nausea. Drug-in­duced bone marrow suppression is a rare side effect, but monitoring CBC results is recom­mended if the patient shows signs of the con­dition or if chloramphenicol therapy is used for extended periods (>4 weeks).

MRSP Illustrated

IN GENERAL

Prognosis

• Prognosis depends on the site and extent of infection; early intervention in surgical wounds and soft-tissue injuries is important. 

• Multidrug-resistant infections often have a poorer prognosis because of the time and ef­fort required to treat them.

Future Considerations

• Minimization or prevention of methicillin re­sistance will require thoughtful use of antibi­otics and consideration of topical agents as first lines of therapy. Treatment based on culture is becoming the standard of care.

*Addendum: Per CLSI guidelines, latex agglutination testing for the altered penicillin binding protein (PBP2a) can be used as a screening testing for methicillin resistance in Staphylococcus spp isolates. Multiple testing methods are preferred to confirm presence of mecA and PBP2a.⁷

MRSA = methicillin-resistant _S aureus, MRSP = methicillin-resistant S pseudintermedius, MRSS = methicillin-resistant _S schleiferi__