Methicillin-Resistant Staphylococcus Aureus in Head and Neck Infections
Yamilet Tirado, M.D.
November 16, 2006

Staphylococcus is a gram-positive cocci that occur individually, in pairs, and in irregular grapelike clusters. The name comes from the Greek term staphyle, which means bunch of grapes. Staphylococcus comes from the bacterial family of Staphylococcaceae, which includes lesser genera such as Gamella, Macrococcus, and Salinicoccus. However, only Staphylococcus aureus and Staphylococcus epidermidis are significant in their interactions with humans, and can be easily identified by the catalase and oxidase test. There are some differences between these main entities. For example, Staphylococcus aureus forms a large yellow colony on rich medium, while Staphylococcus epidermidis forms a small white colony on rich medium. Staphylococcus aureus is hemolytic on blood agar and also produces the enzyme coagulase, while Staphylococcus epidermidis is not hemolytic and lacks this enzyme. Also, Staphylococcus aureus is a potential pathogen, while most strains of Staphylococcus epidermidis are nonpathogenic and play a protective role as normal flora.

In 1928, Alexander Fleming discovered penicillin, using strains of Staphylococcus, while he was working with strains of Staphylococcus aureus. Less than ten years after his discovery, there were strains of Staphylococcus resistant to penicillin. In 1940, hospitals in the United Kingdom and the United States reported that 50% of Staphylococcus aureus was resistant to penicillin. In response to the penicillin-resistant Staphylococcus aureus, newer penicillin derivatives that had beta-lactam rings were created and included methicillin, nafcillin, and ampicillin. By the 1950s, methicillin-resistant Staphylococcus aureus had already emerged. By 1990, MRSA was causing epidemics worldwide and it was recognized that these bugs were not only limited to the hospital environment, but were also found in the community. Nowadays, we are experiencing the new fear of clindamycin and vancomycin resistant strains. This map shows the prevalence of methicillin-resistant Staphylococcus aureus by 1998. As you can see, MRSA is found in most countries, including the United States, most of South America, Europe, and Australia with a prevalence of approximately 25% to 50%. In countries such as Columbia, the prevalence is 50%.

In general, Staphylococcus aureus is one of the most common causes of hospital-acquired infections. The majority of these strains are resistant to penicillin because they produce the beta-lactamase enzymes. The MRSA is a Staphylococcus aureus that is resistant to beta lactam, which includes methicillin, oxacillin, and nafcillin. MRSA accounts for up to 61% of all Staphylococcus aureus infections and the majority of these infections occur in the hospital setting; however, it is becoming more common in the community. Staphylococcus aureus is a common organism carried on the skin, nares, and perineum of healthy individuals. It can cause superficial skin lesions such as impetigo, deep-seated infections such as osteomyelitis, and other systemic infections such as pneumonia, meningitis, or urinary tract infections.

These two studies show the importance of the carrier state of Staphylococcus aureus. In 1995, Wenzel and Perl found that 11% to 32% of the general population are carriers of Staphylococcus aureus and that there is a prevalence of 25% in hospital personnel. Von Eiff, in 2001, showed that in most patients with Staphylococcus aureus bacteremia, the isolates from the patient’s blood were identical to that found in the nares. He also showed three patterns of carriage: the persistent carrier, which is about 50% of the community and is observed more commonly in children; and the intermittent carrier and the no carrier, each of which has a prevalence of 20% in the population. Staphylococcus aureus expresses many potential virulence factors including invasin, membrane-damaging toxins, immunological disguises, surface factors, and superantigens, such as toxic shock syndrome. As we can see here, these are the surface factors that inhibit host phagocytic response, the surface proteins that promote colonization of host tissues, carotenoids and catalase production that enhance survival in phagocytosis, the capsule that inhibits phagocytosis, as well as invasins, immunological disguises, and exotoxins.

This slide shows the pathogenicity of toxic shock syndrome. The superantigen activates the major histocompatibility complex of the antigen-presenting cells, which activates T-cells in a nonspecific way, causing the release of interleukin 1 and tumor necrotic factor, which causes the symptoms of TSS, which includes fever, skin rash, and septic shock.

The evolution of Staphylococcus aureus is predominantly clonal. There are different ways in which it can obtain resistance to antibiotics, including conjugation, transformation, and transduction. Conjugation, as we can see here, occurs when extrachromosomal plasmids from another bacteria are transferred to the bacteria. Transformation is when DNA from an outside environment is incorporated into the bacteria. Transduction is when specific viruses transfer DNA to the bacteria. When the bacteria incorporate these genes it produces proteins that interfere with antibiotic functions. Methicillin resistance is mediated via a chromosomal incorporated resistant gene, which is called mecA gene, which produces a different kind of penicillin-binding protein, interfering with the binding of the beta-lactam antibiotics. This gene is incorporated in a cassette called the staphylococcal cassette, that aids in successful chromosomal incorporation and there are four different types.

MRSA known to cause nosocomial infection is known as hospital-acquired MRSA, while MRSA infections acquired from outside of the hospital are known as community-acquired MRSA. Even though community-acquired and hospital-acquired strains are both MRSA, there are many differences between them. The community-acquired MRSA strain is defined as a positive culture in an outpatient setting or within 48 hours of hospitalization. Hospital-acquired MRSA is a positive culture after 48 hours of hospitalization and, usually the patient has a history of previous hospitalizations, has some association to a nursing home, has had previous surgeries, and also has permanent indwelling catheters. In the community-acquired MRSA, we have seen that the predominant clone is the USA 300, which contains a Panton-Valentine leukocidin gene that produces a toxin that leads to tissue necrosis. Also, the type IV cassette predominates. In the hospital-acquired, the types I through III cassettes predominate. The isolates in community-acquired MRSA are more susceptible to clindamycin and Cipro, while those in hospital-acquired MRSA are multidrug resistant organisms.

USA 300 and USA 400 have accounted for the majority of the community-acquired MRSA infections characterized in the United States. They are associated with a cassette type IV. The USA 100 and USA 200 are the predominant genotypes endemic in the hospital setting and they are associated with cassettes type I through III, which are more easily transferable between Staphylococcus aureus strains. All these clones are differentiated from each other by the pulse-field gel electrophoresis patterns, and, as we can see here, this is the pattern observed in the USA 300. There are two different theories about the etiology of community-acquired MRSA strains. One states that it is a strain that escapes from nosocomial isolates, while the other is that it is a novel community isolate. The Center for Disease Control has identified at risk populations, which include children, military recruits, athletes, prisoners; and the factors that have been associated with outbreaks, including close skin-to-skin contact, openings in the skin, contaminated items, crowded living conditions and poor hygiene.

This is a slide that was provided by Dr. Mason from the Infectious Disease department at Texas Children’s Hospital, which shows the prevalence of methicillin-resistant Staphylococcus aureus noted in the past five years. As you can see, there is an exponential increase of MRSA during these years, while other strains of methicillin-sensitive Staphylococcus aureus have become very stable.

In the head and neck, Staphylococcus aureus including MRSA is well known for causing infections: teeth and soft tissue, ear, nose and paranasal sinuses, oropharyngeal, and the deep neck. For example, this is a patient at Ben Taub who presented with a submental abscess in which the organism was MRSA. This is an example of toxic shock syndrome, which can be a complication of head and neck procedures. Classically, TSS is related to tampon use, but the incidence after laser surgery has been reported at 16 per 100,000. In 1984, Barbour et al published a case report, in which they also pointed out that the vagina and nasopharynx have high staphylococcal colonization rates, and that nasal packing is a soluble culture medium for Staphylococcus aureus and may enhance cytokine production and absorption.

My review of the literature of MRSA Infections in the head and neck was very limited secondary to the small number of cases reported. For example, in this study by Naidu in 2005, there were only four cases of deep neck abscesses caused by MRSA during a one-year period. However, clinically MRSA should be considered as a potential pathogen in deep neck infections, and we should have a high index of suspicion and provide aggressive treatment, including incision and drainage and culture-directed therapy. One of Naidu’s four cases developed mediastinitis as a complication of MRSA infection and therefore, he was the first to describe a case of MRSA mediastinitis in a child. He was also the first to concentrate extensively on pediatric deep neck abscesses with MRSA as a pathogen.

Another interesting study was performed by Coticchia in 2005, which was a retrospective case controlled study to determine the risk factors predisposing to MRSA otorrhea. The study included 70 children with MRSA otorrhea and 19 children with methicillin-sensitive Staphylococcus aureus otorrhea after bilateral myringotomy and tympanostomy tube placement (BMT). He found that the MRSA group had a longer duration of antibiotic treatment after the BMT and also an increased number of episodes of acute otitis media prior to the procedure and increased number of courses of antibiotics after these procedures. Other manifestations of Staphylococcus aureus include internal jugular vein thrombosis, mediastinitis, epiglottitis, and bacteremia.

I want to take this opportunity to present preliminary results of a retrospective study that we are performing on MRSA infections in the head and neck at Texas Children Hospital. Previous reports showed that MRSA accounts for 76% of community-acquired Staphylococcus aureus infections in children at Texas Children. The purpose of our study was to quantify the number of MRSA infections in the head and neck at Texas Children and also identify the clones affecting our patient population. Our methodology included isolates from MRSA head and neck infections identified during the years of 2003 and 2006 that were typed using a pulsed-field gel electrophoresis. Also, medical records were reviewed for culture results and sensitivity, history of previous hospitalization, previous history of Staphylococcus aureus infections, and history of recent surgery. From 134 patients who had Staphylococcus aureus infections in the head and neck, we found 62 patients had positive cultures for MRSA. Eighty-three percent of these infections were disseminated as community-acquired MRSA and 95% of these were identified as USA 300. Thirty percent of isolates were clindamycin-resistant and all cases were sensitive to Bactrim. In our preliminary conclusions, most head and neck MRSA infections are community acquired, USA 300 is the most predominant clone, and clindamycin is the only treatment of choice for this infection. However, some strains are resistant among this population.

The management of Staphylococcus aureus is actually another topic of controversy. When choosing an antimicrobial therapy for skin and soft tissue infections, we should consider that MRSA is the etiologic agent. Also, we need to know the degree of severity of the infection, if the patient has any allergies to medications, and if there is any other underlying disease, such as diabetes and HIV. When indicated, incision and drainage should be performed, and cultures should be obtained. An effective method for the management of MRSA infections is to follow this algorithm. When the patient presents, we need to identify any associated risk factors and assess the severity of the infection. If the patient presents with a very superficial skin infection and is not ill appearing, he can actually be managed as an outpatient, with good choices of oral antibiotics, such as clindamycin and Bactrim for a duration of 7 to 10 days, after which therapy can be adjusted if any cultures have been obtained. However, if the patient does not improve or if the patient presents with a very severe infection, he should be managed in an inpatient setting. If the patient does not have any evidence of abscess, he should be placed on empiric IV antibiotic. If an abscess develop or an abscess was present earlier, an incision and drainage should be performed for cultures and sensitivities, and antibiotic treatment should be adjusted. If there is improvement, the patient can be switched to oral antibiotic therapy with follow-up in two to six weeks.

Methicillin-sensitive Staphylococcus aureus infections can actually be treated with beta-lactam antibiotics or the first generation of cephalosporins, including Keflex and Ancef. MRSA infections can be treated with clindamycin, Linezolid, tetracycline, Bactrim or vancomycin for severe infections. The recommended duration of therapy for simple, uncomplicated infections is 7 to 10 days and, for more severe infections, two to four weeks. This table has data provided by Dr. Mason, and shows that the community-acquired MRSA is 8% resistant to clindamycin, while the hospital-acquired MRSA is 16% resistant. There was no evidence of resistance to vancomycin at TCH, and the Bactrim resistance was very low. This slide, also from Dr. Mason, shows that during the past five years, the resistance of MRSA was 8% in the year 2006, and 16% for hospital-acquired MRSA.

There are many protocols for prevention of MRSA; however, the main point is that we all need to practice good hygiene. Keep hands clean by washing thoroughly with soap and water or using alcohol-based hand sanitizer. For example, this is a picture of Dr. Fagging, who is also contributing to the TCH prevention campaign. Also, wounds should be clean and covered and contact with other people’s wounds should be avoided. We also need to instruct our patients to avoid sharing personal items. Another interesting factor that is currently undergoing investigation is active and passive immunization.

MRSA decolonization is a very controversial topic; however, it has been attempted to in an effort to prevent recurring disease. Decolonization strategies involve systemic antimicrobials such as clindamycin and rifampin, mupirocin nasal ointment, and chlorhexidine body washes during a period of 5 to 7 days. However, convincing evidence of effectiveness of decolonization strategies among MRSA patients is lacking. Also, one of the major fears is the emergence of resistance and for all these reasons, routine attempts at decolonization are not recommended. However, patients with recurrent infections or outbreaks may require some kind of intervention.

In conclusion, community-acquired MRSA is an emerging infectious cause of morbidity among previously healthy individuals. Practitioners should have high indices of suspicion of MRSA as an etiologic agent in head and neck infections. MRSA accounts for 75% of community-acquired infections in children at Texas Children’s Hospital. Infections should be aggressively treated and specific attention should be given to prevention.

Case Presentation:

D.C. is a three-month-old male child without significant past medical history, who presented to Texas Children’s Hospital for evaluation of a right neck mass. His mother noticed that the patient was experiencing cough, difficulty breathing, low grade temperature, decreased oral intake and right neck swelling one day prior to admission. In addition, his vaccines were not up to date and he was living in a shelter with his mother, who had a previous history of drug abuse.

On admission, the patient had a temperature of 100.4°F, was irritable, occasionally lethargic, with inspiratory stridor and increased work of breathing. Upon physical examination, he had thick nasal secretions and a dry oral cavity and oropharynx. He also had right neck swelling measuring 2cm x 2cm with induration, skin erythema, tenderness and decreased neck range of motion. Bedside flexible nasolaryngoscopy revealed swelling of the posterior pharyngeal wall and fullness of the retropharynx, obscuring visualization of the larynx, though the vocal cords appeared to be mobile bilaterally. The rest of his physical exam was unremarkable.

The patient was taken to the operating room by anesthesia and intubated without incident. He was then transferred to the Pediatric Intensive Care Unit for further management. Intravenous clindamycin, nafcillin, gentamycin and vancomycin were started empirically. A CT neck with contrast was performed and revealed a 2cm x 1cm right neck abscess with associated soft tissue swelling and increased fullness in the retropharynx. Laboratory studies revealed a white blood cell count of sixteen thousand and negative blood cultures. The patient was taken back to the operating room for an incision and drainage of the right neck abscess the following day after admission. Cultures obtained at that time grew out methicillin-resistant Staphylococcus aureus. For this reason, all other antibiotics were discotinued, and he was treated only with IV clindamycin.

The patient improved clinically and was extubated on POD #7 and transferred to the floor where he completed a full fourteen day course of IV antibiotics. His symptoms resolved and he was discharged from the hospital.

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