An opportunist pathogen: MRSA (methicillin-resistant Staphylococcus aureus) (Proceedings)

Methicillin is a narrow spectrum beta-lactam antibiotic of the penicillin class. It was first introduced in 1959 for the treatment of penicillin-resistant staphylococcus infections. Staphylococcus aureus, literally the "golden cluster seed" or "the seed gold" and also known as golden staph) is the most common cause of staph infections. It is a spherical bacterium, frequently found in the nose and skin of a person. About 20% of the population are long-term carriers of S. aureus.[1] S. aureus can cause a range of illnesses from minor skin infections, such as pimples, impetigo (may also be caused by Streptococcus pyogenes), boils, cellulitis folliculitis, furuncles, carbuncles, scalded skin syndrome and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, Toxic shock syndrome (TSS), and septicemia. Its incidence is from skin, soft tissue, respiratory, bone, joint, endovascular to wound infections. It is still one of the four most common causes of nosocomial infections, often causing postsurgical wound infections. Abbreviated to S. aureus or Staph aureus in medical literature, S. aureus should not be confused with the similarly named (and also medically relevant) species of the genus Streptococcus. S. aureus was discovered in Aberdeen, Scotland in 1880 by the surgeon Sir Alexander Ogston in pus from surgical abscesses. Each year some 500,000 patients in American hospitals contract a staphylococcal infection.

In 1962, only a little over two years later, the first case of methicillin-resistant staphylococcus aureus (MRSA) was reported. The incidence of MRSA has since escalated in the human population; hospital acquired strains of methicillin-resistant Staphylococcus aureus (HA-MRSA) have become the most prevalent pathogen implicated in nosocomial infections in people worldwide. [Nosocomial infection, are infections which are a result of treatment in a hospital or a healthcare service unit, but secondary to the patient's original condition].

Since the 1970's there have been numerous cases of infections due to MRSA in domesticated animal species. Species that have diagnosed with MRSA include: dogs, cats, horses, cattle, guinea pigs and rabbits. There have been individual reports also in a parrot, bat and turtle. Since then there have been an increasing number of reports of MRSA isolated from companion animals. Prior to 2000, MRSA was rarely isolated. Part of the reason for a perceived increase in MRSA cases in veterinary medicine may be due to increased awareness of this pathogen and increased likelihood that testing (bacterial culture and susceptibility) is performed. However it is also likely that MRSA infections are diseases of emerging importance in companion animal species, particularly dogs, cats and horses.

Patient population/epidemiology/risk

As opposed to humans where the nares and perineum have been identified as the most common sites for these organisms to originate from, a single representative carriage site has not been identified in the dog or cat. This makes identification of the exact prevalence of MRSA in the healthy pet population difficult to determine. In general, the frequency of isolated cases of lower than that of human counterparts most likely because the studies are designed for people and not animals. It is agreed upon though that there is cause for concern for the apparent increase in frequency of MRSA infections in small animals. As with humans, most of these documented infections are associated with post-operative infections and open wounds; however any opportunistic infection has potential to be caused by MRSA.

Pyoderma, otitis and urinary tract infections have also been commonly reported to be the initiating factor. Wound and surgical site infections also appear to be implicated more commonly, especially where implant or other fixation devices are present. Suture material and orthopedic devices act as foreign bodies with a large surface area, lending to an increase potential for bacterial adherence and colonization. Devitalization of tissue also increases the frequency of colonization by this opportunistic pathogen. Additional major risk factors to those listed include: patients with impaired immune systems or chronic illness being treated with steroids, long hospital stays, repeated use of broad-spectrum antibiotics, long surgical procedures as well as owners who work in a human health care settings.

Accessing the biophysical vulnerability of each patient will help prevent poor practices as well as identify those who are particularly at risk.

Zoonosis

There have been numerous studies looking at the transmission of MRSA between humans and animals. There are several noteworthy papers:

(Cross-infection between animals and man: possible feline transmission of Staphylococcus aureus infection in humans? Scott et. al. 1988) An outbreak of epidemic methicillin-resistant Staphylococcus aureus occurred on a rehabilitation geriatric ward. Intensive screening of patients and staff revealed an unusually high carriage rate in the nursing staff (38%), thought to be related to a ward cat which was heavily colonized from the environment. Infection control measures and removal of the cat led to rapid resolution of the outbreak.

(Human carriage of methicillin-resistant Staphylococcus aureus linked with pet dog. Cefai et al 1994). An isolate of MRSA from a patient in an ICU ward prompted screening of the staff. A husband and wife nurse team were found to be carriers of MRSA (nasal). They were treated and tested negative. A second patient contracted MRSA in the unit six months later; repeated screening showed the same couple as carriers. At that point, it was mentioned that their dog had an eye infection for several weeks. Cultures from the dog isolated the same strain of MRSA. Treatment of all 3 (husband, wife and dog) successfully eliminated carriage from all three.

(Asymptomatic nasal carriage of mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) in a pet dog associated with MRSA infection in household contacts. Manian 2003) Recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection in a patient with diabetes and in his wife is described. Culture of nares samples from the family dog grew mupirocin-resistant (minimum inhibitory concentration >1024 microg/mL) MRSA that had a pulsed-field gel electrophoresis chromosomal pattern identical to the MRSA isolated from the patient's nares and his wife's wound. Further recurrence of MRSA infection and nasal colonization in the couple was prevented only after successful eradication of MRSA from the family dog's nares.

(Methicillin-resistant Staphylococcus aureus isolated from a veterinary surgeon and five dogs in one practice.Leonard et al 2006). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from five dogs with wound discharges after surgical procedures at a veterinary practice, and MRSA with similar molecular and phenotypic characteristics was isolated from the nares of one veterinary surgeon in the practice. The pulsed-field gel electrophoresis patterns of all the isolates were indistinguishable from each other and from the most common human isolates of MRSA in Ireland.

(Methicillin-resistant Staphylococcus aureus colonization in veterinary personnel. Hanselman et al 2006). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from nares of 27/417 (6.5%) attendees at the 2005 ACVIM conference: 23/345 (7.0%) veterinarians, 4/34 (12.0%) technicians, and 0/38 others. Colonization was more common for large-animal (15/96, 15.6%) than small-animal personnel (12/271, 4.4%) or those with no animal patient contact (0/50) (p<0.001). Large-animal practice was the only variable significantly associated with colonization (odds ratio 2.9; 95% confidence interval 1.2-6.6). Pulsed-field gel electrophoresis identified 2 predominant clones with similar distribution among veterinarians as previously reported for horses and companion animals. Canadian epidemic MRSA-2 (CMRSA) was isolated from 11 small-animal and 2 large-animal personnel from the United States (n = 12) and Germany (n = 1). In contrast, CMRSA-5 was isolated exclusively from large-animal personnel (p<0.001) in the United States (n = 10), United Kingdom (n = 2), and Denmark (n = 1). MRSA colonization may be an occupational risk for veterinary professionals.

In many, if not most, cases of human-to-animal vs. animal-to-human transmission there is suspicion but not confirmation. There are several additional cases that lend credence to the supposition that both directions of transmission occur. It is fair to say that zoonotic potential is not completely understood.

Prevention and control measures

MRSA is capable of existing on dry, uncleaned surfaces for extended periods by surviving on skin cells that are shed by people in the environment. Skin cells shed constantly from the human body so long sleeves and pants should be worn to reduce the accumulation of dust. Practical approaches to the prevention of MRSA infections are really no different from those in human hospitals. There are several sources to view documents on the control of MRSA such as the CDC (www.cdc.gov/MRSA); these can be adapted easily for our veterinary patients.

It is known that hand washing is key in the control of spread of MRSA and that hand-touch areas such as door handles, telephones, stethoscopes and thermometers are a significant source of contamination. Hand washing with antimicrobial soap and disinfection of surfaces and equipment should be performed between patients. A good rule of thumb is that the hands should be washed every time they collect dirt or debris, and only sanitized if they have come into contact with hand-touch areas. Alcohol gel sanitizers (i.e. Purell) also add a convenient method of hand hygiene. It should be remembered that although the floor is not considered to be an important site of potential infection for people that it may play a role in the spread of MRSA in veterinary care.

Assessing risk is important; once a patient has been identified as being infected or possibly a carrier of MRSA barrier precautions should be used. Wearing of gloves for all contact with these patients should be made routine procedure as should the wearing of masks and gowns for clinical procedures. This clothing should be laundered on-site so as to reduce the risk if transmission. These patients should be isolated upon admission into the hospital and kept away from any immune-compromised patients. As for nursing of these patients an ideal approach is to assign one individual to deal with the MRSA patient(s) who does not have contact with other more critical patients.

Once an animal has been diagnosed or suspected to be a carrier owners should be educated about the potential for zoonotic transmission. It should be well established that contact with an infected or colonized animal may be extremely risky for humans that are either immune-suppressed or that work in the human health care field. People that will be in contact with these patients must be counseled on the importance of barrier precaution and good hygiene practices. These individuals should also be in contact with their own primary care physician so as to minimize their risk.

Treatment

MRSA can be successfully treated if it is identified early and treated correctly. Most fatalities that have occurred thus far have been caused by either delay in diagnosis/treatment and/or being treated improperly. Proper clinical assessment, early detection and treatment with appropriate antibiotics lead to optimal outcomes. When an infection fails to respond or recurs rapidly upon cessation of treatment, standard of care should no longer dictate sequential empirical treatments (i.e. switching from one system antibiotic to the next). Upon clinical suspicion of antimicrobial resistance arises, culture and susceptibility testing should be performed immediately which is essential to positive treatment outcomes. There is good evidence that the use of fluoroquinolones can select for high levels of MRSA. While methicillin and multidrug-resistant strains of staphylococcus are being noted more frequently, there is almost always an option for system treatment. This may require an extended susceptibility panel of antibiotics to include lesser used antibiotics such as chloramphenicol. It should be noted that use of these lesser used medications may cause side effects that are deemed undesirable.

Conclusion

In conclusion, as MRSA continues to be a "hot topic" in veterinary medicine we must be vigilant in educating ourselves about the proper clinical practice associated with it as well as accurate risk assessment, early detection and treatment options so as to ensure that our field of medicine does its best to not repeat the present level of infections of these types seen in human medicine. We must also be careful to consider the ethical complications of using "last resort" treatments as are becoming more commonplace in human medicine. Drugs such as vancomycin and linezolid are fast becoming core treatment choices in highly resistant strains of MRSA in human medicine however the use in veterinary medicine is highly controversial. Many of these drugs are life-threatening and can lead to severe disfigurement in people. There are also increasing reports of resistant strains arising to these "big hitters". In the end, we must use careful, educated judgment to provide the highest quality of care to our veterinary patients so as to provide the highest quality of life to both patient and health care professionals alike.