A Chronic Respiratory Pasteurella multocida Infection Is ...
Transcript of A Chronic Respiratory Pasteurella multocida Infection Is ...
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□ CASE REPORT □
A Chronic Respiratory Pasteurella multocida Infection IsWell-Controlled by Long-Term Macrolide Therapy
Masafumi Seki 1, Tomomi Sakata 2, Masahiro Toyokawa 2, Isao Nishi 2 and Kazunori Tomono 1
Abstract
A 57-year-old woman with severe bronchiectasis frequently received antibiotics, including penicillin, for
acute exacerbations due to Pasteurella multocida. Although the bacteria showed a decrease in antibiotic sus-
ceptibility, her symptoms and X-ray findings became stable, and severe exacerbations were not observed for
the last few years after a low-dose erythromycin treatment was started. The development of a respiratory in-
fection with Pasteurella multocida is relatively uncommon, but it can be controlled by immunomodulation
which is associated with long-term macrolide therapy.
Key words: chronic respiratory infection, macrolides, Pasteurella multocida, opportunistic pathogen
(Intern Med 55: 307-310, 2016)(DOI: 10.2169/internalmedicine.55.4929)
Introduction
Pasteurella species are highly prevalent among animals
and have become one of the most important opportunistic
pathogens that are associated with epizootic outbreaks in hu-
mans (1). Among these species, P. multocida is the most
prevalent in human infections, and it is usually acquired
through contact with animals; including bites, scratches, or
contact with mucous secretions derived from dogs, cats, and
birds (2, 3).
Common symptoms of pasteurellosis on human skin are
swelling, diffuse or localized inflammation with redness and
pain, and bloody or purulent exudate at the animal bite
sites (1, 4). However, it is possible that a respiratory infec-
tion can develop in patients with chronic pulmonary dis-
ease (1, 4, 5). In these cases, pasteurellosis can also present
as a severe bilateral pneumonia and cause lymphadenopathy,
epiglottitis, and abscess formation with increased sputum
and chest pain (5).
In this report, a case of chronic respiratory infection due
to P. multocida with bronchiectasis is described. Bacteria
isolated from the patient’s sputum showed a decrease in an-
tibiotic susceptibility after the patient had received treatment
for frequent exacerbations, but the patient’s condition could
be successfully controlled by long-term macrolide therapy.
Case Report
A 57-year-old woman visited our university hospital in
December 2011 with a cough, chronic sputum, and mild re-
current exertional dyspnea. She had a previous history of se-
vere pneumonia when she was 10 years old and bronchiec-
tasis that affected both lungs (Fig. 1A, D).
Physical examination showed a thin, slightly febrile
woman, with slight clubbing of the fingers and no cyanosis.
Coarse breath sounds and scattered inspiratory rhonchi were
heard throughout both lung fields. Laboratory data included
a WBC count of 6,320/μL (neutrophils 70.3%) and a C-
reactive protein (CRP) level of 0.37 mg/dL.
P. multocida, which is known to colonize dogs, was iso-
lated from her sputum (Fig. 2), and it demonstrated suscep-
tibility to antibiotics at that time (Table). Phagocytosis of
the bacilli was observed, and P. multocida was semi-
quantitatively cultured as (3+), which suggested >107 cfu/mL.
No mycobacterial species or Pseudomonas species were col-
lected from her sputum during the follow-up period. Her
condition was generally good, but she developed frequent
exacerbations every one or two months after the first visit.
She received antibiotics, including oral amoxicillin/clavula-
1Division of Infection Control and Prevention, Osaka University Hospital, Japan and 2Laboratory for Clinical Investigation, Osaka University
Hospital, Japan
Received for publication January 9, 2015; Accepted for publication March 15, 2015
Correspondence to Dr. Masafumi Seki, [email protected]
Intern Med 55: 307-310, 2016 DOI: 10.2169/internalmedicine.55.4929
308
Figure 1. Chest X-ray (A-C) and computed tomography (CT; D-F) images of a 57-year-old woman with chronic Pasteurella multocida infection with bronchiectasis. X-ray and CT images in December 2011 (A, D) show moderate bronchiectasis and granular shadows (arrows), but images in December 2012 (B, E) show severe changes after frequent exacerbations without erythromycin administration during this period. However, images in April 2014 (C, F) are similar to those in December 2012.
A B C
D E F
Figure 2. Gram staining of the sputum from a 57-year-old woman with chronic Pasteurella multocida infection with bron-chiectasis. Many small, Gram-negative, rod-shaped bacilli (ar-rows) are observed with neutrophils (arrowheads). ×1,000.
nate and minocycline, from December 2011 to 2012 in the
outpatient department and became afebrile each time, but
she required home oxygen therapy that started in July 2012.
In December 2012, P. multocida was continuously iso-
lated from her sputum and semi-quantitative culture results
still indicated an abundant amount of P. multocida (3+), even
though she ceased being a pet owner. P. multocida drug sus-
ceptibility decreased, especially to penicillin (Table). Her
chest radiography also showed increased consolidations,
centrilobular granular shadows with mucoid impaction, and
cystic bronchiectasis (Fig. 1B, E).
Due to concerns about the increase in antibiotic resis-
tance, the patient was given oral erythromycin (400 mg/day)
in January 2013, which was half of the usual dose, but ap-
propriate for use as an immunomodulatory drug, although
the isolated P. multocida showed no susceptibility to eryth-
romycin from the start of follow-up for this patient (Table).
After she started to receive the erythromycin, the amount
of sputum did not change and it became serous, although
the number of P. multocida remained high (3+). Furthermore,
no exacerbations with respiratory symptoms had been ob-
served, and the chest imaging results did not reveal a pro-
gression of symptoms in December 2014 (Fig. 1C, F).
Discussion
Pulmonary infections with P. multocida are uncommon,
but there has been a recent increase in the number of such
cases being reported (1). The patients are usually middle-
aged men with a clinical diagnosis of chronic respiratory
diseases, including bronchiectasis. In addition, about 80% of
the reported patients have a history with antecedent expo-
sure to infected animals and pets. Although the present pa-
tient was a woman, her age, underlying pulmonary disease,
and pet history were consistent with previously reported
cases (2, 4).
Intern Med 55: 307-310, 2016 DOI: 10.2169/internalmedicine.55.4929
309
Table. Drug Susceptibility of Pasteurella multocida Isolated from the Patient (sputum).
Date 2011 Dec 2012 Jul 2012 Dec 2013 Jan 2013 May 2013 Dec 2014 Apr Ampicillin 0.25, S 0.5, S 2, R 1, R 2, R >4, R 2, R
Penicillin G 0.12, S 0.5, S 1, R 1, R >4, R 1, R 2, R Ceftriaxon 0.12, S 0.12, S 0.12, S 0.12, S 0.12, S 0.12, S 0.12, S
AMPC/CVA 1, S 1, S 2, R 1, R 1, S 1, R 2, R
Erythromycin >1, R >1, R >1, R >1, R >1, R >1, R >1, R
Clarithromycin >1, R >1, R Azithromycin 2, R 1, S Tetracycline 0.5, S 1, S 0.5, S 0.5, S 2, R 2, R Levofloxacin 0.25, S 0.25, S 0.25, S 0.25, S 0.25, S 0.25, S 0.25, S
Sulfamethoxazole /Trimethoprim 0.5, S 0.5, S 0.5, S 0.5, S 0.5, S 0.5, S 0.5, S
Each number indicates minimum inhibitory concentration (MIC) of each antibiotic for P. multocida.AMPC/CVA: amoxicillin/clavulanate, S: sensitive, R: resistant
P. multocida sometimes causes sepsis and bacteremia in
many animals, but the most common human infection with
P. multocida is a local cellulitis following animal-inflicted
wounds that are related to dogs or cat bites and
scratches (1, 3). Recognition of clinical disease with P. mul-tocida requires a knowledge of its pathogenicity because a
delay in diagnosis may result in the progression of severe
pneumonia and abscess formation (1).
The present patient ceased being a pet owner and received
antibiotics after it was discovered that she had a P. multo-cida infection, but P. multocida continued to be isolated
from her sputum in high numbers (3+) and was resistant to
antibiotics, which made her condition worse. Therefore, a
treatment strategy using something other than antimicrobials
was needed.
It is known that 14 or 15-membered ring macrolides, in-
cluding erythromycin, clarithromycin, and azithromycin, not
only have antibacterial effects, but also immunomodulatory
effects, which frequently result in more host effects rather
than effects against the targeted microorganisms (6-10). The
effects of long-term treatment with macrolide antibiotics
have been demonstrated in clinical and basic research, and
the use of macrolide antibiotics for chronic pulmonary dis-
eases and infections, including diffuse panbronchiolitis
(DPB) (11), as well as other inflammatory airway disorders,
such as cystic fibrosis (CF) are currently being estab-
lished (12).
Macrolides are considered to reduce mucus hypersecretion
and cytokine expression in host factors. Tamaoki et al. re-
ported that macrolides inhibit mucus viscosity by chloride
channel inhibition (13). In addition, we previously reported
the mechanisms of action and effectiveness of these agents
in DPB, lipopolysaccharide (LPS)-related pulmonary disor-
ders, and influenza (6, 8, 9). Macrolides may inhibit the
overproduction of mucin and cytokines in airways, which is
mediated through upstream molecules, including NF-kappa
B and the related mitogen-activated protein (MAP) kinases
in the infected lungs, which decreases inflammation after
treatment.
Furthermore, it has been shown that macrolides control
the cell-to-cell communication or quorum-sensing system in
chronic Pseudomonas aeruginosa infections by regulating
the expression of P. aeruginosa virulence factors (10). In
Pasteurella species including P. multocida, these bacilli also
have similar quorum-sensing systems, and the bacterial cul-
ture supernatants have active molecules that regulate the
autoinducers of their quorum-sensing systems (14). These
data suggest that macrolides might also be able to effec-
tively treat P. multocida-infected patients by mediating the
regulation of quorum-sensing systems in this pathogen.
In conclusion, a case of chronic pulmonary P. multocidainfection with bronchiectasis was herein described. P. multo-cida developed drug-resistance because of recurrent antibi-
otic administration, and furthermore, it was isolated persis-
tently and abundantly. However, the patient’s condition sta-
bilized after erythromycin was administered. Macrolides
may also be useful for P. multocida infection, similar to
chronic Pseudomonas infection and inflammatory lung dis-
eases, including DPB and CF, as immunomodulatory agents,
in addition to their antibiotic effects.
The authors state that they have no Conflict of Interest (COI).
Masafumi Seki and Tomomi Sakata contributed equally to this
work.
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