Infectious Reports 2019; volume 11:8272

Capnocytophaga bacteremia carditis and and is associated precipitating severe thrombo- with bacteremia and sepsis.3 People who are Correspondence: Austin Hopkins, 5511 at increased risk of developing infections Butterfly Lane, Apt 302, Durham NC 27707, cytopenia and preterm labor in with C. canimorsus are asplenic patients USA. an asplenic host and those who chronically use alcohol and Tel: +1.919.271.3811. considered functionally immunocompro- E-mail: [email protected] 4,5 Austin M. Hopkins,1 mised. Infection in is rare how- Key words: Capnocytophaga, thrombocytope- 2 ever, the few case reports published have Nerlyne Desravines, nia, preterm labor. described premature labor, chorioamnioni- Elizabeth M. Stringer,3 Katelin Zahn,2 3 1 tis, and neonatal septicemia associated with Acknowledgments: The authors would like to Carolyn M. Webster, Kayla Krajick, thank the staff of the Maternal Fetal Medicine 3 C. ochracea and other species commonly Neeta L. Vora found in human oral flora.6-9 However, little service for their assistance in the care of the 1University of North Carolina School of is known about the influence of zoonotic- patient presented. Medicine, Chapel Hill, NC; 2Department acquired Capnocytophaga infection during Contributions: AH, manuscript writing, case of Obstetrics & Gynecology, University pregnancy. analysis, and literature review; ND, manu- of North Carolina School of Medicine, script review and case analysis; EMS, manu- Chapel Hill, NC; 3Division of Maternal script review and case analysis; KZ, manu- Fetal Medicine, Department of script review and case analysis; CMW, case Case Report analysis; KK, case analysis; NVL, manuscript Obstetrics & Gynecology, University of review, case analysis. North Carolina School of Medicine, A 35-year-old female (gravida 5, para Chapel Hill, NC, USA 2022) presented to a tertiary care hospital at Conflict of interest: The authors declare no 36 weeks and 2 days gestation with new- potential conflict of interest. onset vaginal and a five-day histo- ry of fevers, headache, neck stiffness, and Funding: None. Abstract altered mental status three days after being onlyReceived for publication: 7 August 2019. bitten by a neighbor’s dog. Her prenatal his- Capnocytophaga species are gram-neg- Revision received: 23 October 2019. tory was significant for fetal intrauterine ative bacilli that inhabit mammalian oral Accepted for publication: 28 October 2019. surfaces and can cause opportunistic infec- growth restriction (IUGR) diagnosed at th tion, especially in asplenic patients. The 32w5d with a fetus weighing 1477guse (5 per- This work is licensed under a Creative species Capnocytophaga canimorsus is par- centile). Her past medical history was sig- Commons Attribution-NonCommercial 4.0 ticularly associated with dog bites and is nificant for a motor vehicular accident in a International License (CC BY-NC 4.0). known to cause endocarditis, meningitis, prior pregnancy with multiple traumatic © and sepsis in the general population. In injuries and resultant splenectomy. She also Copyright: the Author(s), 2019 pregnant patients, infections tied to suffered a diffuse axonal injury with Licensee PAGEPress, Italy loss of short-term memory with a secondary Infectious Disease Reports 2019; 11:8272 Capnocytophaga species from human flora doi:10.4081/idr.2019.8272 have been associated with preterm labor, disorder. In subsequent , , and neonatal septicemia. she required a cesarean delivery due to an 9 There is little known about the effects of unstable pelvis. Prior to admission, she sion was 8×10 /L, which was confirmed zoonotically-acquired Capnocytophaga reported tremulous chills and fevers to with repeat testing. She was transfused prior infection in pregnant patients. In this case 102.7°F (39.3°C). Her husband noted the to surgery with 2 units of platelet and report, we present a patient with patient was off-balance and was slurring her responded appropriately with a count of 9 Capnocytophaga bacteremia acquired after words. She also endorsed new-onset signif- 55×10 /L. In the immediate post-operative a dog bite associated with profound throm- icant fatigue, persistent headache, and tran- period, the patient’s platelet count bocytopenia and preterm labor. Dog bites sient spotting across bilateral visual fields. decreased to 16×109/L, suggesting a throm- are common in the United States, and we The patient then began to experience new bophilia. Routine laboratory screening dur- present basic recommendations Non-commercialfor manage- bright red vaginal bleeding. These symp- ing her pregnancy established a baseline ment of dog bites in pregnant patients in toms prompted the patient’s husband to platelet count of 400×109/L. Initially, there bring her to the tertiary care hospital system order to avoid morbidity associated with was a concern for immune thrombocytope- 1.5 hours away from their home. The delay in time to antibiotic treatment of nia (ITP) or thrombotic thrombocytopenia wound on her index finger from the dog bite infection as described in this case. (TTP), a hematologic emergency requiring appeared to be well-healing with no erythe- plasmapheresis. However, the clinical histo- ma, swelling, or tenderness to palpation. Immediately on presentation, she was ry in this patient suggested an infectious eti- noted to have a persistently category 2 fetal ology and splenic platelet sequestration Introduction heart tracing which was initially attributed impossible given the patient’s lack of a Capnocytophaga spp. are gram-nega- to a placental abruption given her vaginal spleen. tive bacilli that are colonized in mammalian bleeding. She underwent an emergent Hematology evaluation was negative oral flora but may also cause infection fol- repeat low transverse cesarean section. The for schistocytes on peripheral smear and lowing dog or cat bites.1 Capnocytophaga neonate was admitted to the neonatal inten- revealed a normal ADAMST13 level, the canimorsus, (C. canimorsus), is a compo- sive care unit (NICU) and was diagnosed latter of which essentially excluded TTP. nent of canine and feline oral flora and with respiratory failure necessitating intu- However atypical, sepsis with or without infection with C. canimorsus is primarily bation. and core temperature lability with disseminated intravascular coagulation associated with dog bites.2 C. canimorsus is stable hemodynamic vitals. (DIC) became the most likely underlying known to cause infections such as endo- This patient’s platelet count on admis- etiology. She had no evidence of DIC given

[Infectious Disease Reports 2019; 11:8272] [page 37] Case Report normal coagulation studies including a nor- and a fluctuating mental status suggesting platelet count of 8×109/L, suggesting a mal fibrinogen, prothrombin time (PT) and an intracranial component to her symptoms. hematologic pathology. Concurrently, she partial prothrombin time (PTT). In sepsis With her platelet count of less than presented with fevers and altered mental syndromes, platelet counts generally are 70×109/L, a placed her at status following multiple zoonotic expo- lower than 100×109/L with clinical severity high risk for bleeding.14 In discussion with sures. The impact of both processes was associated with the magnitude of the the Maternal Fetal Medicine, Hematology, concerning particularly in the setting of decrease in platelet count, so this patient’s and Infectious Disease teams, the benefits intrauterine growth restriction. profound thrombocytopenia due to infec- and risks of this invasive procedure were tion was not a classic presentation.10 On fur- discussed. The patient’s symptomology was Fetal considerations ther review, she had a remote history of a determined to be more suggestive Perinatal infection with 9 platelet count of 14×10 /L around the time encephalopathy, due to the altered mental Capnocytophaga species is rare with only of the patient’s traumatic MVA five years status being the predominant neurological scattered cases across medical literature with prior. ITP was an additional leading diagno- finding. Lumbar puncture was deferred. An a predominance of focus on species found in sis for her thrombocytopenia that was unre- MRI, in the evaluation of infectious central human flora. Infection with these species are sponsive to transfusion, although the plausi- disease, is a sensitive form a demonstrated potential risk factor for of neuroimaging.15 She underwent an MRI bility of profound platelet destruction by and an infrequent cause of of the brain with contrast which showed no 17 ITP in an asplenic patient was considered chorioamnionitis and . evidence of encephalitis, no acute intracra- unlikely. Following cesarean delivery for Several reported cases involved afebrile nial processes but did note some chronic category 2 fetal heart tracing on arrival, she women who presented in preterm labor with change consistent with her prior brain was started on clindamycin, gentamicin, intact membranes and mild leukocytosis.18-21 injury. and metronidazole due to concern for an Three cases described neonatal morbidity as Blood cultures obtained at infectious process. The asplenic patient is a result of maternal infection.8,22,23 These admission were positive for gram negative an effectively immunocompromised patient reports are based on relatively healthy moth- bacilli and preliminarily grew that lacks cell-mediated immune defenses ers and could suggest that overall, infections and are particularly susceptible to encapsu- Capnocytophaga species and she was con- fromonly human flora Capnocytophaga species lated organisms.11 In the setting of a dog verted to IV ertapenem, a carbapenem beta- are relatively benign with low risk of long- bite, there is a higher risk of pathologic lactam antibiotic, for a 10-day course. term morbidity. infection with canine oral flora, particularly Capnocytophaga canimorsus was eventual- Capnocytophaga. Bacteremia with ly isolated from the cultures. Bacterial iden- Immunocompromised host Capnocytophaga is exceedingly rare but tification was accomplished via MALDI-use Our case uniquely illustrates the poten- potentially serious, with case reports TOF mass spectrometry with 16S rRNA describing a range of 25% - 60% mortality sequencing for verification. The neonate tial gravity of zoonotic Capnocytophaga from sepsis secondary to C. canimorsus.12 was sent to the NICU following delivery infection in an immunocompromised preg- Other considerations in this setting included and was briefly intubated for respiratory nant woman, especially in the setting of rabies. Per the report of the patient’s neigh- distress, but otherwise had no complications asplenia. C. canimorsus was isolated in this bor, the dog was fully vaccinated. After and was discharged to the newborn nursery case and is the most common on the 6th day of life. Blood cultures from Capnocytophaga species associated with quarantine, the dog in question showed no 2 evidence of rabies. On immediate evalua- the neonate were negative. With the admin- dog bites. C. canimorsus has a polysaccha- tion following the dog bite at an urgent care istration of IV antibiotics, the patient’s ride capsule that is implicated in resistance 9 22 facility, rabies prophylaxis had been platelet count recovered to 278×10 /L one to the innate immunity of the host. One deferred due to low suspicion of canine day after starting the IV ertapenem. Her study showed that infection with C. cani- infection. The Infectious Disease specialists profound thrombocytopenia, despite not morsus does not elicit an inflammatory were consulted given the high risk for having a spleen, was attributed to platelet response, and this is potentially due to the pathologic infection with an atypical organ- consumption and decreased platelet produc- protective nature of a polysaccharide struc- ism. As part of a complete workup, she had tion due to C. canimorsus infection. ture from deposition of the complement an x-ray of the finger were unremarkableNon-commercialAlthough the pathogenesis of thrombocy- membrane attack complex and from effi- for acute signs of osteomyelitis. She was topenia in sepsis is largely unknown, there cient phagocytosis by polymorphonuclear 25,26 started on meropenem for antibiotic thera- is some evidence that absolute immature leukocytes (PMNs). This may suggest py, a carbapenem beta-lactam providing platelet count (AIPC) can decrease past the that although the clinical presentation in a broad coverage against both gram positive acute phase of sepsis, suggesting throm- relatively healthy patient may be unremark- bopoietic suppression and a subsequent able, the underlying infection could still be and negative organisms. On a detailed 16 exposure history, the patient was found to decrease in platelet production. The severe, and the risk of infection on both have tick bite in the preceding months as patient was discharged on the sixth hospital maternal and neonatal morbidity during well as contact with goat placenta from day and completed IV ertapenem therapy on pregnancy could be increased with maternal goats that had recently given birth on her an outpatient basis at home. immunocompromise. Our case illustrates an farm, a known harbinger of Coxiella bur- acutely ill patient who is immunocompro- netii, the common cause of Q fever.13 Given mised at baseline. Although she was hemo- the patient’s altered state may have been the dynamically stable, our patient may have result of exposure to tick-borne rickettsial Discussion been in subclinical or atypical sepsis from , she was also started on doxycy- The patient’s asplenia presented a clini- C. canimorsus infection, as seen by fetal cline. cal challenge. This differential diagnosis for distress, dramatic maternal thrombocytope- Another difficulty in this thrombocy- the patient’s clinical illness was particularly nia, labile fevers, central nervous system topenic patient was further evaluation of a extensive given her co-morbidities. She had symptoms, and altered mental status. meningeal process. She had neck stiffness severe thrombocytopenia with an initial

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Severe thrombocytopenia maternal thrombocytopenia, and a brief Rep 2017;18:674-6. The profound thrombocytopenia in this period of neonatal respiratory distress 7.Paerregaard A, Gutschik E. case is of particular interest. Given the mag- requiring intubation, although the latter Capnocytophaga bacteremia complicat- nitude of the depression in platelet counts, finding may be more specifically related to ing premature delivery by cesarean sec- thrombocytopenia in this case was almost prematurity rather than a direct conse- tion. Eur J Clin Microbiol 1987;6:580- certainly not attributable to gestational quence of specific maternal infection. This 1. thrombocytopenia alone.14 Also, gestational case report suggests that both maternal and 8. Mayatepek E, Zilow E, Pohl S. Severe thrombocytopenia is not associated with neonatal effects of C. canimorsus infection intrauterine infection due to symptomatic patients and other findings can be serious, especially with zoonotic- Capnocytophaga ochracea. Biol such as this patient’s altered mental status. acquired infections and with a delay in time Neonate 1991;60:184-6. Thrombotic microangiopathy was unlikely to treatment. As effective and safe treatment 9. Mekouar H, Voortman G, Bernard P, et due to two peripheral smears negative for exists, we recommend that all pregnant al. Capnocytophaga species and perina- schistocytes.27 The patient’s relatively unre- patients who present to any medical tal infections: case report and review of markable ADAMTS13 result essentially provider with dog bite be treated prophylac- literature. Acta Clin Belg 2012;67:42-5. excluded TTP, and ITP is not consistent tically with antibiotics, especially in 10. Claushuis T.A.M., van Vught L.A. with sudden rebound of platelet levels after patients with any form of immunocompro- Thrombocytopenia is associated with a antibiotic administration. DIC is unlikely as mise. For symptomatic pregnant patients, dysregulated host response in critically the patient’s fibrinogen levels remained ele- evaluation in a labor and delivery triage unit ill sepsis patients. Blood vated throughout her course. A possible for fetal monitoring may be necessary. The 2016;127:3062-72. explanation is direct bone marrow suppres- outcomes in this case were favorable, and 11. Ram S, Lewis LA, Rice PA. Infections sion in the setting of fulminant infection or this may be partly due to the arrival of the of People with Complement sepsis, although it is intriguing that the patient to a tertiary care hospital system, Deficiencies and Patients Who Have patient was never classically septic and that where infectious disease, hematological, Undergone Splenectomy. Clin only the platelet cell line was remarkably and neonatal intensive care resources were Microbiol Rev 2010;23:740-80. depressed, as the patient’s red blood cell plentiful and readily accessible. Further 12. Shahani L, Khardori N. Overwhelming research is needed to better understand the only counts were only slightly below normal Capnocytophaga canimorsus infection a mechanism of the profound, isolated range and her white blood cell counts were patient with asplenia. BMJ Case Rep depression of platelet counts during this normal to elevated. 2014;2014:bcr2013202768. patient’s illness. use 13. Roest HJ, van Gelderen B, Dinkla A, et Dog bite al. Q fever in pregnant goats: - Animal bites account for 1% of all esis and excretion of Coxiella burnetii. injury-related emergency department visits PLoS One 2012;7:e48948. and incur more than $50 million in inpatient References 14. American College of Obstetricians and care costs annually.28,29 Most animal bites 1. Brenner DJ, Hollis DG, Fanning GR, Gynecologists. Thrombocytopenia in are from dogs, with most animals being Weaver RE. Capnocytophaga canimor- pregnancy. ACOG Practice Bulletin No. familiar to the victim. Antibiotic prophylax- sus sp. nov. (formerly CDC group DF- 207. Obstet Gynecol 2019;133:e181- is is recommended for patients suffering a 2), a cause of septicemia following dog 93. 15. Maschke M, Kastrup O, Forsting M, dog bite, especially if the patient is bite, and C. cynodegmi sp. nov., a cause Diener HC. Update on neuroimaging in immunosuppressed. Amoxicillin-clavu- of localized wound infection following infectious central nervous system dis- lanate is the first-line antibiotic for treat- dog bit. J Clin Microbiol 1989;27:231- ease. Curr Opin Neurol 2004;17:475. ment of dog bites, and is safe in pregnan- 5. 30,31 16. Koyama K, Katayama S, Muronoi T, et cy. Capnocytophaga infections are cov- 2.Lion C, Escande F, Burdin JC. al. Time course of immature platelet ered by amoxicillin-clavulanate, and early Capnocytophaga canimorsus infections count and its relation to thrombocytope- treatment of infection in our patient may in humans: review of the literature and nia and mortality in patients with sepsis. have prevented the ensuing morbidity, cases report. Eur J Epidemiol 1996;12: PLoS One 2018;13:e0192064. including preterm labor and pretermNon-commercial deliv- 521-33. 17. Lopez E, Raymond J, Patkai J, et al. ery.32 Our patient reported being prescribed 3. Zajkowska J, Krol M, Falkowski D, et Capnotycophaga species and preterm antibiotics to treat her dog bite but was al. Capnocytophaga canimorsus – an birth: case series and review of the liter- instructed not to start her regimen until she underestimated danger after dog or cat ature. Clin Microbiol Infect was able to be seen by her regular Ob/Gyn. bite – review of literature. Przegl 2010:16:1539-43. The delay in time to antibiotic treatment Epidermiol 2016;70:289-95. 18. Ernest JM, Wasilauskas B. may have been the precipitous factor in her 4. Janda JM, Graves MH, Lindquist D, Capnocytophaga in the amniotic fluid preterm labor and delivery. Probert WS. Diagnosing Capnocytophaga canimorsus infections. of a woman in preterm labor with intact Emerg Infect Dis 2006;12:340-2. membranes. Am J Obstet Gynecol 5. Pers C, Gahrn-Hansen B, Frederiksen 1985;153:648-9. W Capnocytophaga canimorsus sep- 19. McDonald H, Gordon DL. Conclusions ticemia in Denmark, 1982–1995: Capnocytophaga species: a cause of Capnocytophaga canimorsus was iden- review of 39 cases. Clin Infect Dis amniotic fluid infection and preterm tified in blood cultures after a dog bite in a 1996;23:71-5. labour. Pathology 1988;20:74-6. pregnant patient with baseline immunocom- 6. Alhifany AA, Almangour TA, Tabb DE, 20. Edwards C, Yi CH, Currie JL. promise due to asplenia. In this case, infec- Levine DH. Premature Labor and Chorioamnionitis caused by tion was associated with fetal distress, Neonatal Septicemia Caused by Capnocytophaga: case report. Am J preterm labor, vaginal bleeding, severe Capnocytophaga Ochracea. Am J Case Obstet Gynecol 1995;173:244-5.

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