Rapidly evolving conjunctivitis due to Pasteurella multocida, occurring after direct inoculation with animal droplets in an immuno-compromised host

Background The rare descriptions, in the literature, of ocular infections due to Pasteurella multocida include: endophtalmitis, keratitis and corneal ulcers, Parinaud’s oculoglandular syndrome, and conjunctivitis. Here, we report a rare case of rapidly evolving conjunctivitis due to Pasteurella multocida, occurring after direct inoculation with animal droplets in an immuno-compromised host. Case presentation A 69-year-old, Caucasian male was referred to our department with purulent conjunctivitis, occurring five days after chemotherapy for an angioimmunoblastic-T-cell-lymphoma, and thirty-three hours after being struck in his right eye by his sneezing Dachshund dog. Physical examination revealed purulent conjunctivitis of the right eye associated with inflammatory edema of both lids. Direct bacteriological examination of conjunctival secretions showed gram-negative bacilli and regular, grey non-hemolytic colonies appearing the next day on blood agar. The oxidase test was positive for these colonies. An antibiotherapy associating intravenous amoxicillin and amoxicillin/clavulanate was administered. The outcome was favorable in the next three days allowing discharge of the patient with amoxicillin (2 g tid per os). Conclusion This case report may be of interest for infectious diseases, ophthalmology or oncology specialists, especially nowadays with chemotherapy being administered in day care centres, where unusual home pathogens can be encountered in health related infections. In this case, previous animal contact and conjunctival samples showing Enterobacteriaceae like colonies with positive oxidase test were two important clues which could help clinicians to make the diagnosis of Pasteurella conjunctivitis in every day practice.


Background
Pasteurella multocida, "killer of multiple species" [1], is a gram-negative rod that is common in the oropharyngeal microflora of numerous animal hosts. It is responsible for fowl cholera in birds and hemorrhagic fever in cattle [2]. In humans, Pasteurella multocida is a common causative agent of dermohypodermitis, tenosynovitis and septic arthritis in immuno-competent and immuno-compromised hosts, usually after dog/cat bites or scratches [2,3]. Device related infections or post-surgical infections due to Pasteurella multocida have also been reported [1,4], but ocular infections due to this bacterium have rarely been described. Indeed, human ocular infections due to Pasteurella genus, including Pasteurella multocida, that are unrelated to animal bites/scratches, have been described in only 12 out of the 3699 infections in a 12-year long British study [5], and 4 out of the 136 human infections in a 3-year long American study [6]. Ocular infections due to Pasteurella multocida, reported in the literature, include endophtalmitis [2,7,8], keratitis and corneal ulcers [6], Parinaud's oculoglandular syndrome [9] and conjunctivitis [10][11][12].
Here, we report a rare case of rapidly evolving conjunctivitis due to Pasteurella multocida, occurring after direct inoculation with animal-derived droplets in an immuno-compromised host.

Case presentation
A 69-year-old Caucasian male was referred to our department for purulent conjunctivitis. He had no past medical history except for an angioimmunoblastic-Tcell-lymphoma, currently treated with chemotherapy, including lenalidomide and CHOP (Cyclophosphamide, Hydroxydaunorubicin, Vincristine, and Prednisone). Five days after his third round of chemotherapy, which he received in day hospital, his Dachshund dog struck his right eye while sneezing. The patient did not feel any pain and confirmed that his dog had not bitten him. Four hours later, his wife noticed redness around his eye and an inflammatory peri-orbital edema, associated with fever reaching 39°C, appeared during the following night. He took no medication. The patient was unable to open his right eye. Upon admission, 33 hours later, physical examination, revealed purulent conjunctivitis with chemosis and conjunctival hyperemia of the right eye associated with inflammatory edema of both the upper and lower lids. Skin rupture and purulent encystment were observed above and below his eye respectively ( Figure 1A). The visual acuity was 3/10 in the right eye and 4/10 in the left eye. Slit lamp instrument examination showed bilateral corticonuclear cataract. Intraocular pressure was 10 mm Hg and the fluorescein eye test were normal in the left eye. The latter tests could not be performed on the right eye. There were neither relative afferent pupillary defects nor extraocular movement abnormalities. The rest of the physical examination was unremarkable. The white blood-cell count was normal (4900/mm3) but the differential revealed lymphopenia (300/mm3). The absolute neutrophil count was within normal range (4400/mm3). A computerized tomography scan revealed no evidence of intra-orbital extension ( Figure 1B). Blood cultures were negative. Conjunctival secretions were sampled on admission for bacteriological analysis and cultured on blood agar. Direct examination showed numerous leukocytes and rare gram-negative bacilli ( Figure 1C). Regular, grey, smooth colonies grew the next day. The oxidase test was positive for the 1-3 mm diameter, non-hemolytic colonies ( Figure 1D&E), strongly suggesting that the isolated strain belonged to Pasteurella genus. The involvement of Pasteurella multocida was also strongly suggested here by mannitol fermentation (API-20E Array) ( Figure 1F) and confirmed by MALDI TOF mass spectrometry. The diagnosis of Pasteurella multocida conjunctivitis with pre septal-cellulitis was therefore retained. Taking into account the animal contact and the short incubation period, suggesting the involvement of Pasteurella genus, an antibiotherapy associating amoxicillin 2 g tid and amoxicillin/clavulanate 2 g tid was administered intravenously, immediately after bacteriological sampling. No topical therapy was prescribed excepted for artificial tears. The outcome was favourable in the next three days ( Figure 1G), allowing discharge of the patient with amoxicillin (2 g tid per os) alone once usual full sensitivity of Pasteurella multocida strain to amoxicillin was confirmed.
Herein, we report a rare case of rapidly evolving conjunctivitis due to Pasteurella multocida, unrelated to animal bite, occurring after direct inoculation with animal-derived droplets, in a host who was immuno-compromised after chemotherapy in daycare centre. The key element in this diagnosis was the animal contact spontaneously described by the patient rather than the classical short incubation time between animal contact and first symptoms [2]. This short incubation time has not clearly been reported in previous conjunctivitis case reports [10][11][12]. In this case we cannot conclude whether this rapidly evolving conjunctivitis was due to the immuno-compromised state of our patient or to the pathogenic potential of the Pasteurella multocida strain itself.
To rapidly assess the presence of such a pathogen, conjunctival secretions were sampled for bacteriological analysis, as suggested by a recent Turkish study that evidenced Pasteurella canis in 4 out of 13 cases of bacterial conjunctivitis resistant to empirical topical antibiotherapy with no history of animal contact [13]. The presence of smooth Enterobacteriaceae-like colonies with positive oxidase test argued in favor of Pasteurella genus. Moreover the involvement of Pasteurella multocida was confirmed by the presence of mannitol fermentation using the API20E Gallery [14] and MALDI TOF mass spectrometry. This bacteriological diagnosis allowed us to validate an antibiotherapy regimen consisting mainly of amoxicillin, which is the drug of choice against Pasteurella strains even if it is unusual in post chemotherapy fever [15]. Indeed, Pasteurella strains are usually fully sensitive to narrow spectrum antibiotics like ampicillin and amoxicillin [14] and reports of penicillinase-producing strains are rare [4]. Here, antibiotherapy associating amoxicillin 2 g tid and amoxicillin/clavulanate 2 g tid was immediately administered intravenously, once bacteriological sampling had been performed, in order to cover all Pasteurella species (including penicillinase-producing strains) as well as staphylococci, streptococci and anaerobes that can be encountered after dog bites [16]. Moreover, such an antibiotherapy was prescribed, despite its poor ocular diffusion, because conjunctivitis without eye involvement was here considered as an infection of soft tissues (such as cellulitis), for which amoxicillin and amoxicillin/clavulanate are strongly recommended [16].

Conclusion
From our point of view, this case report may be of interest for infectious diseases, ophthalmology or oncology specialists nowadays (i) at a time of nationwide antibiotic sparing campaigns and (ii) at a time of ambulatory chemotherapy or chemotherapy in day care centres. The case reported here is an illustration that unusual home pathogens can be encountered in health related infections during these novel chemotherapy processes. In this case, animal contact and conjunctival samples giving Enterobacteriaceae-like colonies with positive oxidase test were two important clues which could help clinicians to make the diagnosis of Pasteurella conjunctivitis in every day practice.