Eur J Clin Microbiol Infect Dis (2003) 22:258–260DOI 10.1007/s10096-003-0891-9

C O N C I S E A R T I C L E

L. Torres · A. I. L�pez · S. Escobar · C. Marne ·M. L. Marco · M. P�rez · J. Verhaegen

Bacteremia by Streptobacillus moniliformis :First Case Described in Spain

Published online: 22 March 2003� Springer-Verlag 2003

Abstract Described here is the case of an 87-year-oldman who developed fever, chills and discomfort causedby Streptobacillus moniliformis. This pathogen is one ofthe causes of rat-bite fever, an uncommon bacterial illnesstransmitted through a bite or scratch from a rodent or theingestion of food or water contaminated with rat faeces.Cases of rat-bite fever are rarely reported in Spain. Thepatient reported no history of rat bite or rodent contact,and the only known risk factor was contact with a dog anda cat that were kept as pets. Streptobacillus moniliformiswas isolated in two sets of blood cultures. This caserepresents what is believed to be the first report ofbacteremia due to Streptobacillus moniliformis in Spain.

Introduction

Rat-bite fever (RBF) is an infectious disease caused bytwo different microorganisms, Streptobacillus monilifor-mis and Spirillum minus, which are commonly found inthe oropharyngeal flora of rodents [1, 2, 3]. Infection canbe acquired through the bite or scratch of a rodent or theingestion of food or water contaminated with rat faeces[2]. The term RBF encompasses three distinct clinicaldisorders caused by two organisms: (i) spirillary RBFcaused by Spirillum minus, which is more frequent in

Asia and called Sodoku; (ii) streptobacillary RBF causedby Streptobacillus moniliformis, which is more commonin North America and Europe; and (iii) Haverhill fever orerythema arthriticum epidemicum, which is caused byStreptobacillus moniliformis after ingestion of milk, foodor water contaminated by the excretions of infected rats[2].

In Spain, the incidence and prevalence of this infectionis unknown. Our search of the medical literature (MED-LINE, January 1965–June 2002, key words: rat-bite fever,Streptobacillus moniliformis) revealed only three cases ofarthritis and one case of a subcutaneous abscess related toRBF in our country [4, 5, 6, 7]. Thus, this report seems torepresent the first case of bacteremia caused by Strepto-bacillus moniliformis in Spain, and the infection occurredin a patient without rodent contact.

Case Report

An 87-year-old man was admitted to our hospital with discomfort,anorexia, weight loss, polyuria, dysuria, slight dehydratation andmild fever of 20 days’ duration. Two sets of blood cultures weretaken and empirical treatment with levofloxacin was initiated. Thepatient became afebrile and was discharged 8 days after hospitaladmission.

Blood cultures were inoculated into Bactec 9240 culture vials(Becton Dickinson, USA) that yielded growth after 2 days ofincubation. A Gram stain demonstrated pleomorphic, filamentousand branching gram-negative bacilli with characteristic bulbousswellings. Subcultures onto Wilkins-Chalgren and chocolate agarunder anaerobic and microaerophilic conditions, respectively, wereperformed. After 72 h a small growth of grey, small, rounded,glistening and buttery colonies was observed on both culture media.

Gram stain of the colonies revealed pleomorphic, long, some-times short, filamentous rods with specific bulbous swellings thatcould fold into curls and loops. Subculture in thioglycolate mediumenriched with 5% foetal calf serum showed typical growth in “puff-ball” colonies (Fig. 1). Biochemical testing revealed the following:positive for arginine dihydrolase activity and negative for oxidase,catalase, urease, indole reaction, lysine and ornithine decarboxyl-ase. All these characteristics pointed to infection with Streptoba-cillus moniliformis.

The strain was sent to the Department of Microbiology of theUniversity Hospitals of Leuven (Belgium), where gas chromatog-raphy of fatty acids was performed. These tests demonstrated the

L. Torres ()) · A. I. L�pez · S. Escobar · C. Marne · M. L. MarcoDepartment of Microbiology,Miguel Servet University Hospital,Paseo Isabel la Cat�lica 1-3, 50009 Zaragoza, Spaine-mail: med023023@saludalia.comTel.: +34-97-6765542

M. P�rezDepartment of Internal Medicine,Miguel Servet University Hospital,Paseo Isabel la Cat�lica 1-3, 50009 Zaragoza, Spain

J. VerhaegenDepartment of Laboratory Medicine, Bacteriology,University Hospitals Leuven, CDG7,Herestraat 49, 3000 Leuven, Belgium

three peaks characteristic of Streptobacillus moniliformis: palmitic(C16:0), stearic (C18:0) and oleic acid (C18:1). Using diskdiffusion with paper disks, the strain was found to be inhibited invitro by penicillin, ampicillin, amoxicillin-clavulanate, cefotaxime,azithromycin, erythromycin, doxycycline, cotrimoxazole, vanco-mycin and teicoplanin. Resistance to polymyxin B, gentamicin,tobramycin, ciprofloxacin and levofloxacin was also revealed.

On questioning, the patient could not recall either a rat bite orcontact with rodents. He lived in an urban area with a dog and a catas pets. No further information about the patient was obtainedfollowing hospital discharge.

Discussion

Human cases of RBF are reported rarely worldwide, andthe true incidence of the disease is unknown [1, 2, 7, 8, 9].Transmission occurs via the bite or scratch of rats [1, 2],but cases have also been associated with bites of mice,squirrels and gerbils and with exposure to animals thatprey on these rodents (e.g., cats and dogs) [1, 2, 9, 10].Persons who are at risk of percutaneous inoculationusually include animal laboratory personnel, children andfarmers [2, 4, 7, 8, 11].

In the case reported here, the patient had no history ofdirect rodent contact and the source of infection wasunclear. The patient lived in the city with a dog and a cat,and these animals have been referred to previously asvectors [1, 2, 10]. It is possible that exposure to these petswas the cause of the infection.

The usual incubation period of RBF is less than 10days, with the beginning of clinical disease usually beingmarked by fever, chills, headache, vomiting, migratingarthralgia and myalgia and a petechial rash [1, 2, 5, 7, 9].In our patient, the only clinical manifestation was fever,and no evidence of arthralgia or rash was found.Complications can include arthritis [5, 6, 7, 8], endocar-ditis [12], pericarditis [13], abscess formation [4], pneu-monia [14] and meningitis [14]. Without adequatetherapy, the illness may persist for a period of months,and the mortality rate is as high as 10% (53% in the caseof endocarditis) [1, 2].

Streptobacillus moniliformis grows slowly over 2–3days, and it prefers microaerophilic conditions (CO2 5–10%) [7, 8]. Culture is difficult to perform, requiringmedia enriched with serum, blood, ascitis or yeast extract[7, 8, 9]. Blood cultures in automatic systems can beunreliable because these systems use polyanethole-sulphonate, an anticoagulant that can inhibit the growthof these bacteria [12, 16]. Nevertheless, we and otherauthors [14] have successfully isolated Streptobacillusmoniliformis using these systems.

Gram stain and typical morphology in solid and liquidmedia can allow a presumptive identification. However,definite identification is based on gas chromatography offatty acids. Recently, a polymerase chain reaction tech-nique has also been developed [15].

The typical susceptibility pattern of the organism issimilar to that of a gram-positive organism, and this cancause some confusion [8]. Streptobacillus moniliformis isusually susceptible to amoxicillin, amoxicillin-clavu-lanate, doxycycline, ceftriaxone, penicillin, oxacillin,vancomycin and erythromycin. Resistance to polymyxinB, aminoglycosides and cotrimoxazole has been reported[8]. Our strain differed in regard to cotrimoxazolesusceptibility. We found no reference to quinoloneresistance. Although our patient’s isolate demonstratedin vitro resistance to quinolones, he was treated empir-ically with levofloxacin upon admission and becameafebrile. However, long-term follow-up was not possible.

Penicillin is the first-choice therapy for RBF at arecommended dose of 1,200,000 U/day for 5–7 daysfollowed by oral penicillin for 7 days. In complicatedcases, such as endocarditis, therapy must be administeredfor 4–6 weeks [1, 6, 8]. When an allergy to penicillinexists, doxycycline is recommended [17].

In conclusion, the diagnosis of RBF is difficult tomake and can be missed. The disease should be includedin the differential diagnosis for all patients with articularpain and irregular relapsing fever. It is important toemphasize the importance of good communication be-tween clinicians and microbiologists, since this is essen-tial in order for a proper diagnosis to be made and forappropiate treatment to be started.

Fig. 1 Typical “puff-ball” colonies in thioglycolate medium

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