Acinetobacter baumannii: Not your typical preseptal cellulitis culprit

Once thought to be of little pathological importance, Acinetobacter baumannii is now recognized as one of the World Health Organization (WHO)’s “priority pathogens,” for its role in opportunistic, multi-drug-resistant (MDR) and life-threatening infections, especially among those in hospitals, nursing homes, on ventilators and with blood catheters. The urgency for new antibiotics is greatest for this pathogen group [1],[2]. In general, A. baumannii is a rare cause of skin and soft tissue infections (SSTIs) and is an even more uncommon cause of preseptal cellulitis. Herein, we describe a case of this infection in an immunocompromised patient and review its risk factors, diagnostic features, and treatment options. To the best of the authors’ knowledge, the literature contains one report of a non-speciated case of Acinetobacter preseptal cellulitis and one caused by Acinetobacter calcoaceticus var. lwoffi, but this is the first reported case caused by A. baumannii [1],[3]. Collection and evaluation of protected patient health information were in compliance with the Health Insurance Portability and Accountability Act of 1996 and adhered to the ethical principles outlined in the Declaration of Helsinki as amended in 2013.

A 61-year-old woman with a medical history of extranodal NK/T-cell lymphoma (on romidepsin chemotherapy) presented for the evaluation of a left upper lid mass associated with erythema and swelling. Her symptoms began three weeks prior, at which time she was diagnosed with a hordeolum by an outside provider. Despite initial conservative management, her swelling and pain increased. On day 4 of symptoms, she visited a local emergency room and underwent an incision and drainage under topical lidocaine. On day 12, she reported continued pain and swelling despite strict adherence to her antibiotic regimen of oral cefdinir, oral sulfamethoxazole/trimethoprim (Bactrim, Frontida Biopharm Inc.) and topical erythromycin ointment. She was subsequently admitted to the hospital. She denied visual disturbances, pain with eye movements, or changes to facial sensation. On initial examination, she was afebrile and without surrounding lymphadenopathy. She had a thickened, irregular left upper lid margin with overlying erythema, edema, and madarosis. There was a palpable, non-fluctuant, mass-like area with active purulent drainage (Figure 1 and Figure 2). She had visual acuities of 20/25 in both eyes, full color vision, normal intraocular pressures, normal pupillary reactions, and unrestricted extraocular muscle movements. The remaining slit lamp and dilated fundus exams were unremarkable.

Serologic workup showed a normal white blood cell count with lymphopenia and neutrophilia, consistent with her lymphoma. In addition, inflammatory markers were elevated with an erythrocyte sedimentation rate (ESR) of 116 and a C-reactive protein (CRP) of 42.2. A computed tomography (CT) scan of the orbits showed uniform soft tissue swelling of the left upper eyelid and supraorbital soft tissues; there was no peripheral enhancement, abscess, post-septal space involvement, or involvement of the adjacent paranasal sinuses (Figure 3). Cultures were taken from the left upper eyelid purulent material and empiric broad-spectrum treatment with IV vancomycin, IV cefepime, and topical tobramycin/dexamethasone (Tobradex, Alcon) was initiated. On day 16, the cultures from the patient’s left eye wound grew A. baumannii, which was isolated using MALDI-TOF (Matrix Assisted Laser Desorption Ionization Time-of-FLIGHT) mass spectrometry (Vitek MS); the specimen had sensitivity to ampicillin/sulbactam, ciprofloxacin, and sulfamethoxazole/trimethoprim. Her antimicrobial therapy was subsequently deescalated to IV ampicillin/sulbactam (Unasyn, Pfizer).

On day 18, due to continued presence of a necrotic exophytic lesion on the left upper eyelid, despite broad spectrum IV antibiotics, the patient underwent surgery for exploration, debridement, and tissue biopsies. A large eschar and underlying necrotic granulation tissue were meticulously removed from the left upper lid. No abscess was found. Pathology specimen showed inflammatory tissue demonstrating a fibrinopurulent exudate with severe suppurative inflammation as well as some areas of overlying reactive squamous epithelial atypia secondary to inflammation. The specimens were negative for malignancy and dysplasia.

Following the wound debridement and antibiotic treatment, the patient’s eyelid improved significantly, with complete closure of the wound defect by two months after the surgery (Figure 4). She had excellent blink and orbicularis function, no lagophthalmos, and a healthy ocular surface.

Acinetobacter species are gram-negative rods that can be found in the environment and are a part of the normal human microbial flora [4]. Acinetobacter baumannii has been associated with severe blood stream infections, urinary tract infections, healthcare- and ventilator-associated pneumonia, and meningitis, and, albeit rarely skin and soft tissue infections (SSTIs) [4],[5]. The rising incidence of A. baumannii SSTIs poses a major public health concern, as these MDR infections confer a high risk of morbidity and rapid mortality to patients [6],[7].

There are several risk factors that should increase one’s clinical index of suspicion for MDR A. baumannii SSTIs. Our patient’s risk factors for this nosocomial infection include advanced age, severe comorbid conditions, treatment with immunosuppressive medications, previous and multiple exposures to antibiotics, and a history of invasive procedure. Other important risk factors include prolonged hospital stays, stay in an intensive care unit (ICU), intubation and mechanical ventilation, a history of trauma or burns, and presence of indwelling catheters [2]. In addition to the typical clinical findings suggestive of a skin infection, there are reports in the literature of recognizable features of A. baumannii cellulitis; it is described initially as developing a “peau d’orange” appearance that progresses to a sandpaper appearance with overlying clear vesicles and ultimately to hemorrhagic bullae and sepsis [4],[8]. Since Acinetobacter species can colonize the skin of healthy individuals and hospitalized patients, a tissue culture is typically required to make the diagnosis. Associated bacteremia can portend a higher disease severity, and as such, blood cultures may also be helpful in making the diagnosis [4].

The multi-drug resistance of A. baumannii poses an important therapeutic challenge. While there are variations in local rates of resistance, host factors, and environmental factors, this pathogen has developed reported resistance to penicillins, cephalosporins, carbapenems, colistin, and quinolones, among others. The mechanisms of resistance include the production of antimicrobial-inactivating enzymes, such as β-lactamases, that inactivate many antibiotics [2]. In addition, Acinetobacter species have intrinsic features that prevent entry or penetration of antimicrobials, such as efflux pumps and absence of outer membrane porins [2]. Moreover, the pathogen’s ability to point-mutate has the potential to decrease antimicrobial affinity and increase the bacteria’s defense mechanisms. These factors, combined with the selective pressure from use of broad-spectrum antibiotics, portend its resistance and therapeutic challenge [2].

Empiric treatment of MDR Acinetobacter SSTIs generally includes a broad-spectrum cephalosporin, β-lactam/β-lactamase inhibitor, or carbapenem as well as consideration of combination therapy [2]. Success of any given antimicrobial agent will depend on several factors including the extent of resistance of the particular bacterial strain, local rates of resistance, type and severity of infection, route of antimicrobial administration, and patient comorbidities. If the specimen is resistant to first-line agents, therapy can be escalated to include polymyxins, tigecycline, or minocycline. In addition to early empiric antimicrobial therapy, timely surgical debridement lends to the successful treatment of A. baumannii SSTIs [4],[8].

The literature contains report of two other cases of Acinetobacter preseptal cellulitis, one caused by A. calcoaceticus var. lwoffi and one that was not speciated [1],[3]. Ours is the first reported case of preseptal cellulitis caused by A. baumannii. All cases presented similarly with either a hordeolum or presumed allergic conjunctivitis that failed initial therapy. Our patient’s case was more severe as she required intravenous antibiotics and surgical debridement in addition to the topical and oral antibiotics required in the other cases. This may be explained by differences in pathogenicity among Acinetobacter species: among infections caused by the Acinetobacter genus, infections caused by A. baumannii are associated with higher mortality and morbidity given its high virulence and extensive antimicrobial resistance [2]. In addition, our patient was immunocompromised, which lends to her risk of more severe disease.

Although rare, preseptal cellulitis caused by A. baumannii can occur and may be rapidly fatal with progression to necrotizing fasciitis and septic shock. When a preseptal cellulitis does not respond to initial antimicrobial therapy, especially in immunocompromised or recently hospitalized patients, tissue should be cultured and tested for resistance. In addition, empiric, broad-spectrum antimicrobials should be initiated promptly and adjunctive surgical debridement should be considered.