Clinical Features of Six Cases of Non-Bite or Scratch Infections by Pasteurella Multocida with the Comparison to 14 Cases with the Infections Caused by Animal Bite or Scratch

  


    
No.

    
Minimum inhibitory concentration (μg/mL)

  

  


    
Penicillin G

    
Ampicillin

    
amoxicillin-clavulanate

    
ceftriaxone

    
cefepime

    
Cefpodoxime Proxetil

    
meropenem

    
levofloxacin

    
clarithromycin

    
azithromycin

    
minocycline

    
Sulfamethoxazole/ trimethoprim

  

  


    
1

    
0.12

    
0.25

    
=0.25

    
=0.25

    
=0.25

    
–

    
=0.06

    
=1

    
2

    
0.5

    
=1

    
=0.12

  

  


    
2

    
0.12

    
0.25

    
=0.12

    
=0.12

    
=0.12

    
=0.12

    
=0.06

    
=0.03

    
8

    
0.5

    
=0.25

    
=0.12

  

  


    
3

    
0.12

    
0.25

    
=0.12

    
=0.12

    
=0.12

    
=0.12

    
=0.06

    
=0.03

    
8

    
0.5

    
=0.25

    
=0.12

  

  


    
4

    
0.12

    
0.25

    
=0.12

    
=0.12

    
=0.12

    
=0.12

    
=0.06

    
=0.03

    
8

    
1

    
=0.25

    
=0.12

  

  


    
5

    
=0.06

    
0.25

    
=0.12

    
=0.12

    
=0.12

    
=0.12

    
=0.06

    
=0.03

    
8

    
0.5

    
=0.25

    
=0.12

  

  


    
6

    
0.12

    
0.25

    
=0.12

    
=0.12

    
=0.12

    
=0.12

    
=0.06

    
=0.03

    
8

    
0.5

    
=0.25

    
=0.12

  

Table 2: Antibiotic susceptibility in Pasteurella multocida.

Case 1 (pneumonia): A 52 years old woman presented to the outpatient office with a recent worsening of productive cough, dyspnea on exertion, and fever elevation (transcutaneous oxygen saturation 96%, white blood cell count [WBC] 11600/mm2, and C-reactive protein [CRP] 4.91 mg/dL). She had been treated as cough variant asthma using budesonide–formoterol for four years. She owed a 12 years old dog kept in door. Sometimes she kissed the dog and shared foods. A Computed Tomography (CT) scan of the thorax revealed bilateral bronchiectasis in the middle lobe/lingular segment, and micronodule shadow especially in the right lower lobe. Isolates showed smooth fluorescent grayish-white colonies with 3–5 mm diameter on blood agar (trypticase soy aga with 5 sheep blood, Nippon Becton Dickinson CO.LTD, Japan). Commercially available identification kits were used for biochemical examination. MALDI-TOF mass spectrometry was also performed to identify P. multocida. As differential diagnosis, Mycobacterium avium-intracellulare Complex was ruled out by biological tests. After amoxicillin therapy for 10 days, P. multocida in sputum was eradicated. Her symptoms were improved. WBC decreased to 6400/mm2 and CRP was 0.61 mg/dL seven days after completion of antibiotic therapy. The radiological abnormal findins in the right lower lobe was also improved. Four weeks later, productive cough was recurred. Maintenance therapy with a low-dose macrolide therapy was started for the exacerbation of pre-existing chronic bronchiolitis with bronchiectasis.

Case 2 (pneumonia): A 70 years old man with chronic renal failure (eGFR 31 mL/min/1.73 m2 on admission). He lost consciousness and collapsed at his house. He was transported to the critical care department, and diagnosed as cerebral infarction with the occlusion of basilar artery. He underwent the intravascular catheter treatment, and ventilator management was required. Although no abnormal finding was demonstrated by chest X-ray examination on admission, Ventilator Associated Pneumonia (VAP) was developed on day 3 (blood temperature 39.0°C, WBC 15470/mm2, and CRP was 2.18 mg/dL). P. multocida was isolated from the sputum. Ampicillin/sulbactam was administered for 10 days, and infection was resolved. He owed no pet in his house, and no injury lesion was detected on his extremities. Although the cause of P. multocida infection was unclear, endogenous infection secondary to preceding respiratory tract colonization was suspected.

Case 3 (pneumonia): A 74 years old man with rectal cancer and lung metastasis and on the home oxygen therapy because of interstitial pneumonia. mediastinal emphysema was detected based on a CT scan examination, and ground-glass appearance was worsened compared with the finding of CT conducted before 30 days. Piperacillin/tazobactam was started, and after confirmation of isolated organisms from the sputum (P. multocida and methicillin-sensitive Staphylococcus aureus), antibiotics was changed to ampicillin/sulbactam. Totally antibiotics was used for 10 days. WBC and CRP were improved from 16830/mm2 and 9.74 mg/dL to 9430/mm2 and 1.11 mg/dL, respectively. He died on day 54 because of underlying cancer disease. There was no record whether he had pets or not.

Case 4 (bacteremia): A 54 years old man with diabetes (HbA1c 9.1%), and liver cirrhosis (Child-Pugh C). He experienced hepatic encephalopathy and hematopoietic stem cell infusion was performed for liver cirrhosis. Because of septic shock and diabetic ketoacidosis (Lactate 15.0 mmol/L), he was transported to the critical care department (BT 39.3°C, WBC 20610/mm2, CRP 9.79 mg/dL, total bilirubin 1.7 mg/dL, AST/ALT 234/99 IU/L). On the CT scan, no apparent focus for sepsis including pneumonia was identified. He owed a dog. Although, there was no recent episode of the bite, the dog licked his eye a few days ago. P. multocida was isolated form the blood and nasal swab. Negative culture for P. multocida was conformed in the specimen from sputum, urine and tear from the eye. Piperacillin/tazobactam was used as initial empiric therapy, and changed to ampicillin/sulbactam after identification of P. multocida in the blood culture, and totally antibiotics was used for 14 days. Clinical course was good and patient discharged on day 19. Although nasal colonization of P. multocida was demonstrated, the source of bacteremia was undetermined.

Case 5 (cellulitis occurred from the diabetes foot ulcer): A 56 years old man with diabetes foot ulcer on the second toe presented to the emergency department (BT 37.2°C, WBC 7130/mm2, CRP 4.24 mg/dL). He complained the worsening of the ulcer with pain and swelling. He bumped the site against the desk several days before. P. multocida, methicillin-resistant Staphylococcus aureus and Streptococcus oralis were isolated from the wound. He did not have pet and there was no episode of animal exposure. Levofloxacin followed by minocycline was administered for 14 days. Wound infection was resolved without the development of osteomyelitis.

Case 6 (cellulitis on the right hand): A 68 years old woman with diabetes and normal pressure hydrocephalus (cerebrospinal fluid shunt). She injured on her thumb of right hand with a fall on the road. Although the open wound was small, the wound worsened with purulent discharge and pain and swelling She consulted on day 3 (BT 37.3°C; WBC 13020/mm2: and CRP 7.4 mg/dL). P. multocida, Methicillin-resistant Staphylococcus aureus, and Streptococcus oralis were isolated from the wound. She had no pet, and there was no episode of animal contact including B/S. Wound was irrigated and levofloxacin followed by minocycline was administered for 28 days totally.

Discussion

We reported six non-B/S infections by P. multocida. Pasteurella pneumonia was developed in two patients with chronic pulmonary disease and in one patient with chronic renal failure who were managed by ventilator after the attack of cerebral infarction. Bacteremia was occurred in a patient with liver cirrhosis (Child-Pugh C) and diabetes. Although nasal colonization of P. multocida was demonstrated, the source of bacteremia was not determined. In addition, a patient with diabetes and normal pressure hydrocephalus who had toe injury with a fall, and a patient with diabetes foot ulcer had cellulitis.

P. multocida was identified exclusively using MALDI-TOF mass spectrometry in all six non-B/S infections, while identification kits were used in 13 of 14 patients with B/S infections. In addition, non-B/S infections were found only in the recent five years over 10-years study period. Kormondi et al. [3] found that the number of isolates and human pasteurellosis cases has increased from year to year. Considering that pathogenicity or antibiotic susceptibility have not been changed in P. multocida [14], possible explanation for the increasing tendency is the development of microbiological methods for identification, such as use of MALDI-TOF mass spectrometry and molecular methods. Although earlier automated identification systems provided adequate identification of Pasteurella strains, pasteurellosis might have been overlooked in the absence of animal B/S especially in patients who did not have a household animal.

Although non-B/S infections could be associated with licks, inhalation leading to respiratory tract colonization, contamination of open wounds, contamination of food with pet saliva by the sharing, and incidental pet exposure, the possible cause was not determined in a considerable number of patients [2]. In our series, three of six patients did not owe a pet and there was no apparent animal exposure (case 2, 5, and 6). Respiratory tract can be colonized by P. multocida with above-mentioned deep animal contact. VAP by P. multocida was developed in patient underwent therapy for cerebral infarction (case 2). Endogenous infections secondary to preceding respiratory tract colonization was suspected in this case. Although the source was not determined, bacteremia was developed in a patient with nasal colonization (case 4).

Patients with open wound is vulnerable to non-B/S pasteurellosis. We experienced two patients in whom cellulitis was developed because of the contamination of the wound except for B/S. Pet owners with open wounds must protect them from infection from the pet saliva either with the direct licking or the contaminated environment such as carpet. Non-B/S infection is more serious than B/S infections. Giodarno et al. [4] reported that four patients were died and 7 patients admitted intensive care unit among 19 patients with non-B/S infections. Patients with non-B/S infections were more frequently bacteremic, hospitalized more often, and frequently had comorbidities than those with B/S infections [2]. Although patients with animal bite are treated early by a physician, non-B/S infections are diagnosed and treated after the patients become sick, and the culture reports were available.

Although pneumonia by P. multocida could be developed in patients with chronic obstructive pulmonary disease who are otherwise-immunocompetence [9,16], non-B/S infections such as bacteremia [17], meningitis [11], intraabdominal infections [12,18] occur exclusively in immunocompromised hosts. Chatelier et al. [17] reviewed 119 proven cases of P. multocida bacteremia. The most common comorbidities were cirrhosis, immunosuppressive therapy, and malignant diseases. Kobayaa et al. [19] reported 2 newborns developing meningitis after incidental pet exposure. There are several reports of peritonitis in patients with peritoneal dialysis [2,18]. In conclusion, Pasteurella pneumonia in patients with underlying pulmonary disease, and Pasteurella skin and soft tissue infections in patients who have chronic open wounds should be ruled out as differential diagnosis, if the patient owes household pets. Moreover, clinicians should not overlook pasteurellosis in immunocompromised hosts even if patients deny having animal contact. Different from B/S infections, non-B/S infections by P. multocida should be assumed as opportunistic infections.

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