ENFOQUE DE GESTIÓN DE RIESGO

Over the last century, common pathogens in orbital cel- lulitis have changed. Human activity has played the pre- dominant role in changing the microbiology of infections. From vaccines to antibiotics, there has been a profound change in the organisms responsible for causing human morbidity. Measles, mumps, rubella, smallpox, and chicken pox are many of the scourges no longer readily seen by physicians. As mentioned, H. infl uenza as of 20 years ago was a prominent, and oft en devastating, organ- ism involved in a variety of head and neck infections, periorbital cellulitis included. All of these passed to the footnotes of history due to vaccinations.

In addition, the introduction of antibiotics has changed the behavior of bacteria as they evolve in the ongoing battle with humankind. Th e most prevalent problem in the early twenty-fi rst century is MRSA [5, 38, 48]. Th e changing epidemiology of MRSA in both the hospitalized and community populations mirrors the emergence of penicillin-resistant strains of S. aureus

decades ago. Penicillin was fi rst introduced in 1941, and soon thereaft er penicillin resistance among hospitalized patients was being reported. By the end of World War II, most hospital-acquired strains of S. aureus were resistant to penicillin. Th is is largely attributed to previ- ous fi rst-line treatment with beta-lactam antibiotics in these patient populations [55]. Over several decades, most S. aureus infections in the hospitals fi rst and then later in the community became equally resistant to pen- icillin [5].

In a similar manner, methicillin was introduced as a treatment for S. aureus in 1961, and in less than 1 year, resistance to methicillin was reported in the hospital set- ting [38]. Initially, large urban tertiary care centers suf- fered MRSA rates of 10% or less, while smaller community-based institutions were largely unaff ected. Within 25–30 years, over 20% of S. aureus strains in these smaller, nonreferral centers were resistant to methicillin, as were over 40% in larger urban institutions. By 1998, resistance reached 50% in hospital settings, and soon aft er, rates of resistance in the community-based population quickly rose. Currently, rates of hospital-acquired MRSA are well over 80%, with recent exponential rises in several epidemiologic studies from around the United States.

Infections due to community-acquired MRSA (CA-MRSA) have been reported all over the world and have been exponentially growing in incidence [10, 14, 22, 49, 55]. Based on the aforementioned epidemiology of penicillin resistance, the CA-MRSA should exponentially continue to increase over the next decade. Studies between 1995 and 2006 showed CA-MRSA rates increasing from about 20% to about 60% in patients presenting with soft tissue infections [22, 33, 38]. A study found 68% of staph- ylococcal isolates from periorbital cellulitis were methi- cillin resistant [23].

10.5.1 CA-MRSA Versus Hospital-Acquired MRSA

Th e most likely mechanism of methicillin resistance in S. aureus comes secondary to the presence of the mecA gene complex, which transcribes a penicillin-binding protein that has multiple insertion sequences within its targeted DNA fragment [11, 22]. Th is mechanism accounts for the resistance of hospital-acquired MRSA to many antibiotics. Although it has variations of these genes, CA-MRSA is comparably susceptible to many non-beta-lactam antibiot- ics and can typically be successfully treated with a variety of available antibiotics, including tetracyclines, vancomy- cin, clindamycin, and sulfa-based drugs [22, 48, 49]. Th is

Summary for the Clinician

Th e most common bacterial isolates in orbital ■

cellulitis include the Staphylococcus species. Coagulase-negative

■ Staphylococcus and S. aureus

are common causes of both preseptal cellulitis and postseptal infection.

Pseudomonas

■ species, Streptococcus species, Moraxella catarrhalis, and Ekinella corrodens are all less-common causes of orbital cellulitis.

is largely because fewer S. aureus strains are exposed to broad-spectrum antibiotics in the community, and multi- ple-drug-resistant strains therefore have less of a survival advantage. Th e mecA gene translation is thought to vary accordingly.

Distinctive strains within the community and hospital groups have been confi rmed diff erent in studies using pulsed-fi eld gel electrophoresis. Health care-associated MRSA and CA-MRSA diff er in that the former tends to carry mec types I, II, and III, and the latter encodes mec type IV [39, 54]. By far the prominent among these CA-MRSA strains is the USA300 clone. Pathologic exami- nation of the MRSA USA300 clone, a community-acquired strain, shows extensive tissue necrosis due to its Panton– Valentine leukocidin gene held within its mec IV chromo- some-containing cassette [5, 17, 29, 36, 38, 48, 49]. Th is gene encodes an exotoxin that has been shown in vitro to destroy polymorpholeukocytes and macrophages. More recent research elucidated that the USA300 clone viru- lence may be attributable to diff erential expression of core genome-encoded virulence determinants, such as phe- nol-soluble modulins and alpha-toxin and not just the panton valentine leukocidin toxin (PVL) gene [34].

While providing a histologic diff erence between MRSA types, this virulent clone is also blurring the lines between hospital-acquired MRSA and CA-MRSA [39, 48]. Th ere have been reports internationally of its outbreak within health centers. Th e term community-associated infection may eventually be more appropriate for these MRSA strains. Regardless, despite their diff erences, both hospital and community strains can progress to severe soft tissue infections, necrotizing infections, systemic illness, osteo- myelitis, bacteremia, and death even in healthy adults.

Given the past epidemiologic trends regarding the time course of penicillin and methicillin resistance and the aforementioned genetic evolution of MRSA, one would assume the eventual rise of vancomycin-resistant S. aureus (VISA) in the community setting is inevitable. In fact, there is now a growing prevalence of clindamycin resistance as well as hospital-acquired VISA infections [3]. Th e Centers for Disease Control and Prevention (CDC) has already confi rmed a number of cases of VISA-related deaths.

10.5.2 Orbital MRSA

One of the most common bacterial isolates in many ocular infections historically includes the S. aureus species, so one may have predicted that MRSA would emerge as an increasingly common etiology of ophthalmic ailments. To be sure, MRSA has become a more frequently reported cause of lid abscess (Fig. 10.3), dacryocystitis, endophthal- mitis, panophthalmitis, and superior ophthalmic vein thrombosis [13, 23, 31]. It has also been isolated as a source of conjunctivitis and keratitis in patients with underlying surface disease, poor overall health, malignancies, and operative interventions, including cataract, LASIK, and retinal surgeries [9, 15, 16, 28, 41, 46, 47, 51, 52].

Summary for the Clinician

Th e introduction of antibiotics has changed the ■

behavior of bacteria as they evolve in the ongo- ing battle with humankind.

Th e most prevalent problem in the early twenty- ■

fi rst century is MRSA.

Currently, rates of hospital-acquired MRSA are ■

well over 80%.

Infections due to CA-MRSA have been reported ■

all over the world and have been exponentially growing in incidence.

Th e most likely mechanism of methicillin resis- ■

tance in S. aureus comes secondary to the pres- ence of the mecA gene complex, which transcribes a penicillin-binding protein that has multiple insertion sequences within its targeted DNA fragment.

Th is mechanism accounts for the resistance of ■

hospital-acquired MRSA to many antibiotics. Although it has variations of these genes, ■

CA-MRSA is comparably susceptible to many non-beta-lactam antibiotics and can typically be successfully treated with a variety of available antibiotics, including tetracyclines, vancomycin,

clindamycin, and sulfa-based drugs. Fig. 10.3 Young woman with acute onset of focal abscess and preseptal cellulitis that cultured positive for MRSA

10

MRSA has also been reported as an increasingly com- mon pathogen in orbital cellulitis [11]. However, little is known about CA-MRSA infections of the eye and orbit [1, 25, 27, 32, 40, 42, 43, 50, 56, 57]. Most of what we know is limited to case reports, and the majority of these CA-MRSA infections involved the USA300 clone. In almost all community-acquired cases described in the current literature, this disease quickly assumes a down- hill clinical course. In some cases, even with appropriate antibiotic treatment and surgical debridement, some patients are left with signifi cant morbidity from extensive tissue necrosis, including blindness or the need for enucleation.

Our personal experience at the Wills Eye Institute ini- tially was derived from ten consecutive cases of postsep- tal MRSA identifi ed from March 2006 through February 2008, with more and more cases presenting aft er the anal- ysis. Th is initial cohort represents cases seen at several hospitals in the Philadelphia area as well as cases seen in an outpatient offi ce setting. Th e average age of this initial cohort was 28.9 years, with a bimodal distribution rang- ing from 6 weeks to 61 years.

Patients were diagnosed and monitored with both clinical examination and CT scanning. Th e younger cohort of patients had focal, superfi cial abscesses with surrounding cellulitis that were drained and treated with oral antibiotics. Th ese patients all required just one sur- gical intervention. Th e exception to this was a 6-week- old infant who was transferred to Children’s Hospital of Philadelphia with a signifi cant orbital cellulitis that appeared to arise from a local wound to the lower eyelid and spread into the subperiosteal space. She required prolonged intravenous antibiotics and two trips to the operating room, but eventually settled without sequelae.

Th e adult patients had more aggressive infections that spread along tissue planes with multiple microabscesses and a true tissue cellulitis (Fig. 10.4a, b). Th ese more aggressive infections required hospitalization, intrave- nous antibiotics, and oft en multiple surgeries to debride the infections. On average, each of these older patients had two surgical debridements to bring the infections under control. Because of the more severe nature of some of these infections, their slow responses to antibiotics, and the infl ammatory eff ects of surgery, steroids were added in three of fi ve adult cases. In these cases, corti- costeroids noticeably helped patients improve and recover.

Inpatient management included vancomycin in all our patients, typically in conjunction with a second drug. Th ese combinations were always chosen and managed by the infectious disease team, which was invaluable. In addition, most of these patients were sent home with prolonged 2- to 4-week courses of intravenous vancomy- cin via a peripherally inserted central catheter. All ten patients returned to baseline, although some with resid- ual scarring. Two of the adult patients had residual pto- sis, one of which was treated, and the other is still being followed.