Sepsis by Pasteurella multocida in an Elderly Immunocompetent Patient after a Cat Bite

Pasteurella multocida colonizes animal scratches and bites. This bacterium was described to cause sepsis or endocarditis mainly in immunocompromised patients. We report the case of a 92-year-old woman presenting at the Emergency Department with coma and fever a week after the bite of her cat. The cat bite was misdiagnosed at admission partly due to an underestimation of this event by the patient's relatives. An inflamed area localized at perimalleolar skin of the right leg was detected. Laboratory biomarkers of inflammation were elevated. The cerebral computed tomography (CT) scan with angiographic sequences showed a complete occlusion of right intracranial vertebral artery. Total body CT scan and abdominal echocardiography were negative for foci of infection. Three consecutive blood cultures were positive for Pasteurella multocida. A diagnosis of sepsis by Pasteurella multocida was made, and the patient recovered after a specific antimicrobial treatment. In order to confirm the animal transmission, the cat saliva was cultured and found positive for Pasteurella multocida with a similar antibiotic sensitivity to that isolated from the patient. In conclusion, the case of a patient with coma and fever after a cat bite was presented. The transmission of pathogens from pets has to be carefully considered as an important route of infection in immunocompetent patients.


Introduction
Pasteurella multocida is a Gram-negative coccobacillus frequently isolated in the upper respiratory tract and gastrointestinal microbiota of many animals. Speci cally, cats showed the highest carriage rate among pets, ranging from 70 to 90%. Animal scratches and bites are the most common sources of human Pasteurella infections and expression of the disease may vary from mild local symptoms to lifethreatening conditions, such as septic shock. We present a case of sepsis and coma in an elderly immunocompetent woman due to Pasteurella multocida after a cat bite.

Case Report
A 92-year-old woman was accompanied to the Emergency Department in a coma status (Glasgow Coma Scale (GCS) of 7) with feces loss and fever (39.5°C). Blood pressure was 180/110 mmHg, the respiratory rate was 25 breaths/minute, and arterial blood oxygen saturation was 92% while breathing on room air. Furthermore, the physical examination revealed a systolic mitralic murmur and an in amed area on perimalleolar skin on the right leg ( Figure 1). e personal medical history included hypertension, mild cognitive impairment related to vascular encephalopathy, chronic atrial brillation, chronic heart failure, and bleeding complications after falls during anticoagulant therapy. e patient did not take any immunosuppressive or anti-in ammatory drug at home. At admission, the electrocardiogram (ECG) con rmed atrial brillation with normal heart rate. Laboratory blood tests demonstrated a white blood cell count (WBC) of 13,160/mm 3 , haemoglobin of 159 g/L, lactic acid of 2.5 mmol/L, creatinine of 0.7 mg/dL, troponin I of 0.238 μg/L, C-reactive protein (CRP) of 6.2 mg/L, and lactic dehydrogenase of 252 U/L. e brain computed tomography (CT) scan with angiographic sequences demonstrated the complete occlusion of the right intracranial vertebral artery, di used signs of leukoencephalopathy, and no haemorrhages (Figure 2(a)). e brain magnetic resonance imaging (MRI) excluded a recent cerebral ischemia but conrmed the occlusion of the right intracranial vertebral artery (Figure 2(b)). Total body CT scan was not able to detect any macroscopic foci of infection or cancer. e Doppler ultrasound examination of leg arteries and veins as well as carotid arteries did not detect any thrombosis and/or stenosis. Blood cultures were performed and, while waiting for the isolation time, an empirical antimicrobial treatment with piperacillin/ tazobactam was started together with supportive therapies. No signi cant clinical improvement was observed, and inammatory biomarkers, such as procalcitonin (with a peak of 4.0 µg/L) and CRP (with a peak of 200 mg/L), increased. On the other hand, troponin I blood concentration rapidly reached the normal values.
A targeted antimicrobial therapy with ampicillin-sulbactam was immediately started, in association with gentamicin in order to obtain a synergistic antimicrobial activity in consideration of the possible diagnosis of endocarditis. After one day of such a therapy, the patient's consciousness restored and the fever stopped. On day four after the admission, three blood cultures resulted positive for Gram-negative coccobacilli. In the Microbiology Laboratory, blood samples were collected and inoculated in BD BACTEC ™ Plus Aerobic/F and Anaerobic/F culture vials and incubated in the automated system BD BACTEC. Positive aerobic specimens were seeded on blood and chocolate agar plates, giving round, grey, nonhaemolytic, nonmucoid pure colonies after 24 hours. Bacterial stain was identi ed as Pasteurella multocida with the automated biochemical testing Vitek 2 (BioMeriéux Italia S.p.A., Grassina, Italy), which also performed antibiotic sensitivity, indicated in Table 1. Identi cation was con rmed with the matrix-assisted laser desorption ionization time-of-ight mass spectrometry (MALDI-TOF) VITEK MS (BioMeriéux Italia S.p.A.). e transthoracic echocardiogram on day 10 did not show any endocarditic lesions, and the patient completely recovered. In the meanwhile, the patient could refer about the skin lesion due to her cat bite, occurring one week before her hospital admission. Since the cat was still living at the patient's home, a sample of its saliva was analyzed.
In particular, a cat pharyngeal swab was performed and seeded on blood and chocolate agar plates and grew at 37°C in aerobic condition. After 24 hours, mixed bacterial colonies grew, from which an isolation on blood agar was performed to grow in anaerobic condition. e anaerobic growth gave the sole colonies the same look as the ones isolated from patient blood culture. Colonies from cat were identi ed as Pasteurella multocida through the same technologies, that is, the automated biochemical testing and the mass spectrometry. e antibiotic sensitivity of cat strain was analyzed with the Vitek system as well. e phenotype of sensitivity of the patient strain and cat strain was the same, and the related MIC values were similar (Table 1). In particular, cefotaxime MIC value of patient isolates was < 1 mg/L, while that of cat isolates was 1 mg/L. Such a quantitative diversity corresponds to the variability achievable with a strain alone (Table 1). e patient was discharged after 15 days of antimicrobial therapy (ampicillin/sulbactam and gentamicin). Additional blood cultures during antibiotic treatment were negative, and procalcitonin and CRP levels were reduced to 0.09 µg/L and 33.6 mg/L, respectively. Additional 15-day treatment with amoxicillin and clavulanic acid was recommended at  Case Reports in Infectious Diseases home. During hospitalization, the patient underwent anticoagulation therapy for elevated ischemic stroke risk (CHA DS -VASc Score: 7 points) since the beginning of deambulation. en, due to the HAS-BLED Score 3 points, the high risk of falls and previous fall-related major bleeding complications during anticoagulation therapy, the patient was discharged without an anticoagulant therapy. After one-year follow-up, the patient regained her prehospitalization life without any additional neurological impairment. However, she preferred to avoid living with a pet. e patient formally approved the publication of this anonymized case report and signed the informed consent.

Discussion
Skin infections due to cat bites are commonly due to Pasteurella. Rarely, the local disease can lead to sepsis or septic shock [1][2][3][4][5]. In general, people a ected by these severe forms are aged over 65 years or have comorbidities (such as diabetes and immunodepression) [3,6,7]. After a cat bite, a proper cleaning of the wound and the initiation of a broad spectrum antibiotic therapy are recommended. Since animal bites potentially deliver a polymicrobial infection [8][9][10], a combination of amoxicillin and the β-lactamase inhibitor (clavulanic acid) or doxycycline plus metronidazole (for patients with penicillin allergies), or clindamycin plus a uoroquinolone (i.e., cipro oxacin), should be recommended [10]. Rarely, penicillin-resistant Pasteurella was described in human infections [11]. Since this kind of infection can be treated with common antibiotics at home, many people consider cat bites and scratches not dangerous and do not advise family physician or do not refer to this event when admitted to hospital.
In the abovementioned case report, the patient did not su er from diabetes or any other known immunode ciency. At the complete interview, she reported to be bitten twice from her cat in the previous month: the rst time presenting an acute local infection that spontaneously recovered, and the second time with a septic fever needing hospitalization. We might also speculate on the vertebral artery thrombosis diagnosed by brain CT scan and MRI, although clinically silent.
is nding could be attributed either to a septic embolus or to a cardio embolization related to chronic atrial brillation. Since the patient recovered, she preferred not to perform any additional neuroimaging during follow-up.
is point remains to be clari ed. Interestingly, our patient did not respond to piperacillin-tazobactam treatment, even though piperacillin shows a good in vitro activity against Pasteurella [12]. We do not have any clear explanation for this nding. Possibly, the dosage used in our case (2.25 g three times per day calculated on the creatinine clearance) did not allow to reach e ectively therapeutic plasma levels. Sepsis by P. multocida is rare but not an extraordinary event. us, our interest just emerged after the awareness of the possible link between sepsis and the wound due to a cat bite. Having not collected the patient strain, we could not perform comparative sequence analysis to denitively con rm that the P. multocida source was from the cat. We used the similarity between the antibacterial sensitivity phenotype of the strains, from the patient and cat, to presume that the identity of microorganisms was the same.
is trait, along with the lacking of strains serotyping, is a limit of our report. Anyway, the temporal concordance of the events and the diagnostic elements in our possession allow us to think that the correlation we posed is not risky and worthy of being noti ed. From the microbiological point of view, it is interesting to note that we achieved isolation of Pasteurella, among cat pharyngeal microbiota, only by incubating blood and chocolate agar plates in anaerobic conditions, without the employment of selective media. It is likely that, being a facultative anaerobe organism, P. multocida has bene ted from conditions unfavorable for other bacteria present in the cat oral mucosa. In conclusion, the cat bites and scratches can drive many pathogenic bacteria, such as Pasteurella multocida, and cause deep wounds, especially on the legs and arms. Usually, these lesions are treated with a local approach and are often underestimated by people. Only in few circumstances, patients require a medical examination and begin a proper antibiotic treatment. In elderly patients, especially when a ected by other comorbidities, cat bites can lead to local complications or even to a Pasteurella multocida sepsis, the latter being an unusual, albeit severe condition. A wider awareness of this problem may be useful in order to prevent life-threatening conditions after pet bites [13], especially in elderly people. e importance of a prompt antibiotic administration should also be underlined. In case of fever after cat bite or scratch and suspected poor compliance to antibiotic therapy, hospitalization may be required.

Conflicts of Interest
e authors state that they have no con icts of interest.

Authors' Contributions
All authors had access to the data and contributed to writing the manuscript.