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Pediatrics International (2014) 56, e79–e81
doi: 10.1111/ped.12432
Patient Report
Prolonged incubation period in neonatal Pasteurella multocida meningitis and bacteremia Hiroshi Yamaguchi, Takuya Tamura, Michiko Abe, Shigetoshi Ogiwara, Shuji Sai, Kiyotaka Kosugiyama, Akemi Sugihara, Kiyoshi Nagumo, Seido Iwata and Yoshikazu Kinugawa Department of Pediatrics, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan Abstract
Pasteurella multocida, often found as part of the human oral flora and in finger/toenails, also exists in many animals, especially cats, dogs, and pigs. Although rare, pasteurella infection in neonates can cause serious systemic disease, such as meningitis. In this article, a 23-day-old girl presented with decreased appetite and irritability for >2 days. Eighteen days previously her pet cat had jumped onto the left side of her head while she was sleeping. On laboratory data C-reactive protein was high, and on cerebrospinal fluid (CSF) analysis leukocyte count was extremely high, with low glucose and high protein. P. multocida grew out of the blood and CSF cultures, and she was successfully treated with antibiotics for 3 weeks. Although pasteurellosis rarely occurs, it can sometimes lead to life-threatening situations, so parents should exercise caution when having pets around their children.
Key words meningitis, newborn, Pasteurella multocida.
In Japan, with the current popularity of pets, the percentage of families owning a domestic cat was reported to be approximately 10.2% in 2012.1 Pasteurella multocida, a Gram-negative coccobacillus usually found as part of the human oral flora or in finger/toenails, also exists in many animals, especially cats, dogs, and pigs.2 It is usually transmitted by bite or scratch wounds from domestic animals,2,3 but human-to-human horizontal transmission has been reported as another route of infection in neonates.4 Pasteurella infection in neonates causes serious systemic disease leading to meningitis, septicemia, pneumonia, conjunctivitis, and osteoarticular infection.3 Because meningitis and bacteremia rarely occur in humans, definitive treatment has not been set. Interestingly, more than half of the previously published case reports have not described any history of animal contact and, surprisingly, pasteurella meningitis due to cat scratch has been only rarely reported.3 In this report, the successful treatment of a neonate with meningitis and bacteremia caused by P. multocida after an 18 day incubation period is described. To the best of our knowledge, this English-language case report is the first in Japan regarding this diagnosis.
Case report A 23-day-old girl presented with a >2 day history of decreased appetite and irritability. She was born at 37 weeks 0 days’
Correspondence: Hiroshi Yamaguchi, MD DVM, 1 Jo 12-1-40, Maeda, Teine-ku, Sapporo 006-8555, Japan. Email: sunamausu_kyu @oasis.ocn.ne.jp Received 20 March 2014; revised 8 May 2014; accepted 9 June 2014.
© 2014 Japan Pediatric Society
gestation at 2442 g via emergency cesarean section due to preeclampsia. The delivery had no complications, and she was discharged after 4 days. Two days later, however, her pet cat jumped onto the left side of her head while she was sleeping; the wound bled slightly. Her mother then took her to the local clinic where the wound was disinfected with a topical antiseptic agent. At this point, she had no further contact with the cat, but she started to have decreased appetite and irritability. On admission, temperature was 38.5°C, heart rate 185 beats/ min, blood pressure 120/70 mmHg, respiratory rate 60 breaths/ min, and room air oxygen saturation 100%. Generally, she was irritable and crying. Head/neck exam showed no bulging anterior fontanelle, and neurologic examination was unremarkable. Skin exam indicated a 0.5 cm round red crust on her left temporal region with no surrounding erythema, edema, or induration; also no abscess or perforation of the skull requiring drainage or debridement was present (Fig. 1). Laboratory results were as follows: white blood cell count, 8500/mm3 with 4335/mm3 neutrophils; hemoglobin, 9.0 g/dL; and platelets, 493 000/mm3; C-reactive protein was 15 mg/dL (normal, 0–0.3 mg/dL). Serum chemistry and urinalysis were normal. On analysis of cerebrospinal fluid (CSF), leukocytes were 21 280/mm3 (predominantly polymorphonuclear cells, 60%) with glucose 3 mg/dL (normal, 40–75 mg/dL) and protein 465 mg/dL (normal, 5–60 mg/dL). Gram stain and CSF cultures were pending at that point. Given a diagnosis of bacterial meningitis, the patient was started on ampicillin (300 mg/kg per day) and cefotaxime (200 mg/kg per day). The following day, Streptococcus pneumonia growth was confirmed on CSF culture, therefore treatment was changed to cefotaxime (200 mg/kg per day) and vancomycin (40 mg/kg per day). On the third day, a second lumbar puncture
e80
H Yamaguchi et al. indicated turbid CSF containing 1178/mm3 leukocytes (predominantly polymorphonuclear cells) with glucose 27 mg/dL and protein 237 mg/dL; CSF Gram stain and cultures showed no growth. The next day, additional reports from the first CSF culture confirmed Gram-negative coccobacillus, not S. pneumonia, therefore treatment was again changed to cefepime (150 mg/kg per day). On the fifth day, final CSF and blood culture reports identified pan-sensitive P. multocida. Given the diagnosis of P. multocida meningitis and bacteremia, treatment was narrowed down to high-dose ampicillin (300 mg/kg per day). During this time, the patient clinically improved despite temperature fluctuations between 37 and 38.5°C for >2 weeks (Fig. 2), and head magnetic resonance imaging (MRI) showed no abnormalities, such as subdural empyema. Antibiotic treatment was discontinued after 3 weeks. During that period, intact neurological exam and auditory brainstem response were confirmed along with laboratory and radiological improvement, as shown on blood tests, third lumbar puncture, and another head MRI. She was finally discharged without complications after 3 weeks.
Fig. 1 Small red crust on temporal region.
40 39 T (°C)
38 37 36 35
10 5
CRP
25000 20000 WBC (/µL)
CRP (mg/dL)
15
15000 10000 5000
0
WBC
0
CSF Cell count (/mm3) Protein (mg/dL) Sugar (mg/dL)
21 280 465 3
1178 237 27
40 179 31
P.multocida In blood and CSF CFPM VCM CTX ABPC 1
2
3
4
5
6
Drug susceptibility
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Days after admission
Fig. 2 Time course of treatment. ABPC, ampicillin; CFPM, cefepime; CRP, C-reactive protein; CSF, cerebrospinal fluid; CTX, cefotaxime; VCM, vancomycin. © 2014 Japan Pediatric Society
Pasteurella multocida incubation period Discussion Neonatal pasteurella meningitis, a rare but serious bacterial infection, has a relatively high mortality rate.5 Nakwan et al. reported on neonatal pasteurellosis and its major risk factors in animal exposure to cats and/or dogs: non-traumatic exposure in 44% of cases, vertical transmission in 44% of cases, and, surprisingly, traumatic exposure in only 8% of cases (two bite cases).3 Pasteurella meningitis due to cat scratch, therefore, is indeed a very rare condition. In the present case, it is surprising that the patient presented 18 days after having been scratched by her pet cat. Schuur et al. reported on a 4-month-old’s development of pasteurella meningitis 5 days after a cat jumped on her head with subsequent scratches. They did not ascribe her meningitis to hematogenous seeding from a local wound infection because blood cultures were negative;6 instead, they suspected that the cat’s claws perforated her posterior fontanelle with subsequent direct incubation of P. multocida into the CSF. A literature search, however, produced no previous information on the incubation period of pasteurella meningitis and bacteremia from a local infection, as opposed to direct incubation after cat scratch, so to the best of our knowledge, this article is the first to provide details on incubation period. The duration of fever typically lasts 4–6 days after the initiation of adequate therapy.7,8 Fever lasting >5 days occurs in approximately 13% of patients, while recurrence of fever after being afebrile for ≥24 h occurs in approximately 16%.8 Persistent fever >8 days and secondary fever have a number of causes, including inadequate treatment, development of nosocomial infection, discontinuation of dexamethasone, development of a suppurative complication (pericarditis, pneumonia, arthritis, subdural empyema), and drug fever.9 In many cases, a specific cause of prolonged fever cannot be determined. In the present patient a high fever persisted for 18 days, but she had no nosocomial infection (as confirmed on repeat CSF analysis), no dexamethasone use, and no suppurative complication. Although drug fever is suspected, the cause of persistent fever in the setting of clinical improvement was deemed to be due to the individual’s host response to infection. The antibiotic therapy of choice for pasteurellosis in children is usually penicillin, with high doses used in neonates with central nervous system infection. The recommended duration of treatment is 7–10 days for local infection and 2 weeks for neonatal bacteremia and meningitis.3 Because some case reports
e81
noted a duration of 3 weeks,5 the present patient also received 3 weeks of therapy due to persistent fever.10 Although pasteurella infections are usually acquired through scratch or bite wounds from domestic animals or through vertical transmission in neonates,2–4 it is a very rare condition. Pediatricians may advise parents to clip their pet’s nails, prevent the pet’s entrance into the baby’s bedroom, and wash their hands after touching their pets. Despite the uncommonness of pasteurella infections, however, parents should still exercise caution when having pets around their children due to the possible lifethreatening complications of the infection.
Acknowledgment We thank Dr Christine Kwan for her assistance with the manuscript.
References 1 Japan Pet Food Association. The survey of domestic dogs and cats in 2012 in Japan. [Cited 2002.] Available from URL: http:// www.petfood.or.jp/data/chart2012/index.html. 2 Weber DJ, Wolfson JS, Swart MN. Pasteurella multocida infections: Report of 34 cases and review of the literature. Medicine 1984; 63: 133–54. 3 Nakwan N, Nakwan N, Atta T, Chokephaibulkit K. Neonatal pasteurellosis: A review of reported cases. Arch. Dis. Child. Fetal Neonatal Ed. 2009; 94: 373–6. 4 Siahanidou T, Gika G, Skiathitou AV et al. Pasteurella multocida infection in a neonate: Evidence for a human-to-human horizontal transmission. Pediatr. Infect. Dis. J. 2012; 31: 536–7. 5 Green BT, Ramsey KM, Nolan PE. Pasteurella multocida meningitis: Case report and review of the last 11 y. (Review). Scand. J. Infect. Dis. 2002; 34: 213–17. 6 Schuur PM, Haring AJ, van Belkum A, Draaisma JM, Buiting AG. Use of random amplification of polymorphic DNA in a case of Pasteurella multocida meningitis that occurred following a cat scratch on the head. Clin. Infect. Dis. 1997; 24: 1004–6. 7 Arditi M, Herold BC, Yogev R. Cefuroxime treatment failure and Haemophilus influenzae meningitis: Case report and review of literature. Pediatrics 1989; 84: 132–5. 8 Lin TY, Nelson JD, McCracken GH Jr. Fever during treatment for bacterial meningitis. Pediatr. Infect. Dis. 1984; 3: 319–22. 9 Klein JO, Feigin RD, McCracken GH Jr. Report of the task force on diagnosis and management of meningitis. Pediatrics 1986; 78 (5 Pt 2): 959–82. 10 Pickering LK, Baker CJ, Long SS, American Academy of Pediatrics. Pasteurella Infection. Redbook: Report of the Committee on Infectious Diseases, 27th edn. American Academy of Pediatrics, Elk Grove Village, IL, 2006; 487–8.
© 2014 Japan Pediatric Society
Pediatrics International (2014) 56, e79–e81
doi: 10.1111/ped.12432
Patient Report
Prolonged incubation period in neonatal Pasteurella multocida meningitis and bacteremia Hiroshi Yamaguchi, Takuya Tamura, Michiko Abe, Shigetoshi Ogiwara, Shuji Sai, Kiyotaka Kosugiyama, Akemi Sugihara, Kiyoshi Nagumo, Seido Iwata and Yoshikazu Kinugawa Department of Pediatrics, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan Abstract
Pasteurella multocida, often found as part of the human oral flora and in finger/toenails, also exists in many animals, especially cats, dogs, and pigs. Although rare, pasteurella infection in neonates can cause serious systemic disease, such as meningitis. In this article, a 23-day-old girl presented with decreased appetite and irritability for >2 days. Eighteen days previously her pet cat had jumped onto the left side of her head while she was sleeping. On laboratory data C-reactive protein was high, and on cerebrospinal fluid (CSF) analysis leukocyte count was extremely high, with low glucose and high protein. P. multocida grew out of the blood and CSF cultures, and she was successfully treated with antibiotics for 3 weeks. Although pasteurellosis rarely occurs, it can sometimes lead to life-threatening situations, so parents should exercise caution when having pets around their children.
Key words meningitis, newborn, Pasteurella multocida.
In Japan, with the current popularity of pets, the percentage of families owning a domestic cat was reported to be approximately 10.2% in 2012.1 Pasteurella multocida, a Gram-negative coccobacillus usually found as part of the human oral flora or in finger/toenails, also exists in many animals, especially cats, dogs, and pigs.2 It is usually transmitted by bite or scratch wounds from domestic animals,2,3 but human-to-human horizontal transmission has been reported as another route of infection in neonates.4 Pasteurella infection in neonates causes serious systemic disease leading to meningitis, septicemia, pneumonia, conjunctivitis, and osteoarticular infection.3 Because meningitis and bacteremia rarely occur in humans, definitive treatment has not been set. Interestingly, more than half of the previously published case reports have not described any history of animal contact and, surprisingly, pasteurella meningitis due to cat scratch has been only rarely reported.3 In this report, the successful treatment of a neonate with meningitis and bacteremia caused by P. multocida after an 18 day incubation period is described. To the best of our knowledge, this English-language case report is the first in Japan regarding this diagnosis.
Case report A 23-day-old girl presented with a >2 day history of decreased appetite and irritability. She was born at 37 weeks 0 days’
Correspondence: Hiroshi Yamaguchi, MD DVM, 1 Jo 12-1-40, Maeda, Teine-ku, Sapporo 006-8555, Japan. Email: sunamausu_kyu @oasis.ocn.ne.jp Received 20 March 2014; revised 8 May 2014; accepted 9 June 2014.
© 2014 Japan Pediatric Society
gestation at 2442 g via emergency cesarean section due to preeclampsia. The delivery had no complications, and she was discharged after 4 days. Two days later, however, her pet cat jumped onto the left side of her head while she was sleeping; the wound bled slightly. Her mother then took her to the local clinic where the wound was disinfected with a topical antiseptic agent. At this point, she had no further contact with the cat, but she started to have decreased appetite and irritability. On admission, temperature was 38.5°C, heart rate 185 beats/ min, blood pressure 120/70 mmHg, respiratory rate 60 breaths/ min, and room air oxygen saturation 100%. Generally, she was irritable and crying. Head/neck exam showed no bulging anterior fontanelle, and neurologic examination was unremarkable. Skin exam indicated a 0.5 cm round red crust on her left temporal region with no surrounding erythema, edema, or induration; also no abscess or perforation of the skull requiring drainage or debridement was present (Fig. 1). Laboratory results were as follows: white blood cell count, 8500/mm3 with 4335/mm3 neutrophils; hemoglobin, 9.0 g/dL; and platelets, 493 000/mm3; C-reactive protein was 15 mg/dL (normal, 0–0.3 mg/dL). Serum chemistry and urinalysis were normal. On analysis of cerebrospinal fluid (CSF), leukocytes were 21 280/mm3 (predominantly polymorphonuclear cells, 60%) with glucose 3 mg/dL (normal, 40–75 mg/dL) and protein 465 mg/dL (normal, 5–60 mg/dL). Gram stain and CSF cultures were pending at that point. Given a diagnosis of bacterial meningitis, the patient was started on ampicillin (300 mg/kg per day) and cefotaxime (200 mg/kg per day). The following day, Streptococcus pneumonia growth was confirmed on CSF culture, therefore treatment was changed to cefotaxime (200 mg/kg per day) and vancomycin (40 mg/kg per day). On the third day, a second lumbar puncture
e80
H Yamaguchi et al. indicated turbid CSF containing 1178/mm3 leukocytes (predominantly polymorphonuclear cells) with glucose 27 mg/dL and protein 237 mg/dL; CSF Gram stain and cultures showed no growth. The next day, additional reports from the first CSF culture confirmed Gram-negative coccobacillus, not S. pneumonia, therefore treatment was again changed to cefepime (150 mg/kg per day). On the fifth day, final CSF and blood culture reports identified pan-sensitive P. multocida. Given the diagnosis of P. multocida meningitis and bacteremia, treatment was narrowed down to high-dose ampicillin (300 mg/kg per day). During this time, the patient clinically improved despite temperature fluctuations between 37 and 38.5°C for >2 weeks (Fig. 2), and head magnetic resonance imaging (MRI) showed no abnormalities, such as subdural empyema. Antibiotic treatment was discontinued after 3 weeks. During that period, intact neurological exam and auditory brainstem response were confirmed along with laboratory and radiological improvement, as shown on blood tests, third lumbar puncture, and another head MRI. She was finally discharged without complications after 3 weeks.
Fig. 1 Small red crust on temporal region.
40 39 T (°C)
38 37 36 35
10 5
CRP
25000 20000 WBC (/µL)
CRP (mg/dL)
15
15000 10000 5000
0
WBC
0
CSF Cell count (/mm3) Protein (mg/dL) Sugar (mg/dL)
21 280 465 3
1178 237 27
40 179 31
P.multocida In blood and CSF CFPM VCM CTX ABPC 1
2
3
4
5
6
Drug susceptibility
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Days after admission
Fig. 2 Time course of treatment. ABPC, ampicillin; CFPM, cefepime; CRP, C-reactive protein; CSF, cerebrospinal fluid; CTX, cefotaxime; VCM, vancomycin. © 2014 Japan Pediatric Society
Pasteurella multocida incubation period Discussion Neonatal pasteurella meningitis, a rare but serious bacterial infection, has a relatively high mortality rate.5 Nakwan et al. reported on neonatal pasteurellosis and its major risk factors in animal exposure to cats and/or dogs: non-traumatic exposure in 44% of cases, vertical transmission in 44% of cases, and, surprisingly, traumatic exposure in only 8% of cases (two bite cases).3 Pasteurella meningitis due to cat scratch, therefore, is indeed a very rare condition. In the present case, it is surprising that the patient presented 18 days after having been scratched by her pet cat. Schuur et al. reported on a 4-month-old’s development of pasteurella meningitis 5 days after a cat jumped on her head with subsequent scratches. They did not ascribe her meningitis to hematogenous seeding from a local wound infection because blood cultures were negative;6 instead, they suspected that the cat’s claws perforated her posterior fontanelle with subsequent direct incubation of P. multocida into the CSF. A literature search, however, produced no previous information on the incubation period of pasteurella meningitis and bacteremia from a local infection, as opposed to direct incubation after cat scratch, so to the best of our knowledge, this article is the first to provide details on incubation period. The duration of fever typically lasts 4–6 days after the initiation of adequate therapy.7,8 Fever lasting >5 days occurs in approximately 13% of patients, while recurrence of fever after being afebrile for ≥24 h occurs in approximately 16%.8 Persistent fever >8 days and secondary fever have a number of causes, including inadequate treatment, development of nosocomial infection, discontinuation of dexamethasone, development of a suppurative complication (pericarditis, pneumonia, arthritis, subdural empyema), and drug fever.9 In many cases, a specific cause of prolonged fever cannot be determined. In the present patient a high fever persisted for 18 days, but she had no nosocomial infection (as confirmed on repeat CSF analysis), no dexamethasone use, and no suppurative complication. Although drug fever is suspected, the cause of persistent fever in the setting of clinical improvement was deemed to be due to the individual’s host response to infection. The antibiotic therapy of choice for pasteurellosis in children is usually penicillin, with high doses used in neonates with central nervous system infection. The recommended duration of treatment is 7–10 days for local infection and 2 weeks for neonatal bacteremia and meningitis.3 Because some case reports
e81
noted a duration of 3 weeks,5 the present patient also received 3 weeks of therapy due to persistent fever.10 Although pasteurella infections are usually acquired through scratch or bite wounds from domestic animals or through vertical transmission in neonates,2–4 it is a very rare condition. Pediatricians may advise parents to clip their pet’s nails, prevent the pet’s entrance into the baby’s bedroom, and wash their hands after touching their pets. Despite the uncommonness of pasteurella infections, however, parents should still exercise caution when having pets around their children due to the possible lifethreatening complications of the infection.
Acknowledgment We thank Dr Christine Kwan for her assistance with the manuscript.
References 1 Japan Pet Food Association. The survey of domestic dogs and cats in 2012 in Japan. [Cited 2002.] Available from URL: http:// www.petfood.or.jp/data/chart2012/index.html. 2 Weber DJ, Wolfson JS, Swart MN. Pasteurella multocida infections: Report of 34 cases and review of the literature. Medicine 1984; 63: 133–54. 3 Nakwan N, Nakwan N, Atta T, Chokephaibulkit K. Neonatal pasteurellosis: A review of reported cases. Arch. Dis. Child. Fetal Neonatal Ed. 2009; 94: 373–6. 4 Siahanidou T, Gika G, Skiathitou AV et al. Pasteurella multocida infection in a neonate: Evidence for a human-to-human horizontal transmission. Pediatr. Infect. Dis. J. 2012; 31: 536–7. 5 Green BT, Ramsey KM, Nolan PE. Pasteurella multocida meningitis: Case report and review of the last 11 y. (Review). Scand. J. Infect. Dis. 2002; 34: 213–17. 6 Schuur PM, Haring AJ, van Belkum A, Draaisma JM, Buiting AG. Use of random amplification of polymorphic DNA in a case of Pasteurella multocida meningitis that occurred following a cat scratch on the head. Clin. Infect. Dis. 1997; 24: 1004–6. 7 Arditi M, Herold BC, Yogev R. Cefuroxime treatment failure and Haemophilus influenzae meningitis: Case report and review of literature. Pediatrics 1989; 84: 132–5. 8 Lin TY, Nelson JD, McCracken GH Jr. Fever during treatment for bacterial meningitis. Pediatr. Infect. Dis. 1984; 3: 319–22. 9 Klein JO, Feigin RD, McCracken GH Jr. Report of the task force on diagnosis and management of meningitis. Pediatrics 1986; 78 (5 Pt 2): 959–82. 10 Pickering LK, Baker CJ, Long SS, American Academy of Pediatrics. Pasteurella Infection. Redbook: Report of the Committee on Infectious Diseases, 27th edn. American Academy of Pediatrics, Elk Grove Village, IL, 2006; 487–8.
© 2014 Japan Pediatric Society
