Infectious Disease Reports 2016; volume 8:6368

Erysipelothrix rhusiopathiae several weeks.2 Human disease is classified into three forms: a localized cutaneous form Correspondence: Francesco Luzzaro, bacteremia without (erysipeloid) caused by traumatic penetration Microbiology and Virology Unit, A. Manzoni : rapid of E. rhusiopathiae, a generalized cutaneous Hospital, Via dell’Eremo 9/11, 23900 Lecco, Italy. identification from positive form and a septicemic form. The latter type of Tel.: +39.0341.489630 - Fax: +39.0341.489601. disease has been previously associated with a E-mail: [email protected] blood culture by MALDI-TOF high incidence of endocarditis. In a previous Key words: ; skin and soft tissue infec- mass spectrometry. A case study concerning invasive cases tions; antimicrobial treatment; empirical therapy. since 1912, it was reported that about 90% of report and literature review Contributions: LP performed laboratory diagnosis cases of E. rhusiopathiae bacteremia result in and drafted the manuscript; SB, CM and BP per- 3 Luigi Principe, Silvia Bracco, endocarditis. This association has been formed susceptibility tests, analysed data and Carola Mauri, Silvia Tonolo, Beatrice Pini, recently questioned, since some cases of E. contributed to laboratory diagnosis; ST provided Francesco Luzzaro rhusiopathiae bacteremia without subsequent clinical information about the patient; FL con- endocarditis have been reported in the most ceived of the study, participated in its design and Microbiology and Virology Unit, A. recent literature.4-8 Here we report a case of E. coordination, and critically revised the draft man- Manzoni Hospital, Lecco, Italy rhusiopathiae bacteremia, probably started uscript. from an erysipeloid form, in which endocardi- tis did not develop. Furthermore, we used the Conflict of interest: the authors declare no poten- PubMed Database to search for recent case tial conflict of interest. Abstract reports of bloodstream caused by E. Received for publication: 17 December 2015. rhusiopathiae. Revision received: 25 January 2016. Erysipelothrix rhusiopathiae is a Gram-posi- Accepted for publication: 25 January 2016. tive that is infrequently responsible for infections in humans. Three forms have This work is licensed under a Creative Commons been classified: a localized cutaneous form Case Report Attribution-NonCommercial 4.0 International (erysipeloid) caused by traumatic penetration Licenseonly (CC BY-NC 4.0). of E. rhusiopathiae, a generalized cutaneous An Italian citizen (male, 74 years old) pre- form and a septicemic form. The latter type of ©Copyright L. Principe et al., 2016 sented to the emergency department of the Licensee PAGEPress, Italy disease has been previously associated with a San Leopoldo Mandic Hospital in Merate Infectious Disease Reports 2016; 8:6368 high incidence of endocarditis. Here we report (Lecco, Italy) on August, 2014. The patientuse was doi:10.4081/idr.2016.6368 a case of E. rhusiopathiae bacteremia in a 74- in treatment with oral anticoagulant therapy year-old man, probably started from an due to cardiopathy and cerebral vasculopathy. erysipeloid form, in which endocarditis did not On admission, he had a low grade fever develop. This case presents some particular (38.4°C), hearth rate 100 beats per minute, and uncommon features: i) no correlation with blood pressure 125/75 mm of Hg, white blood was performed directly from positive blood cul- animal source; ii) correlation between bac- cell count 4.2×109/L. In addition, he showed ture bottle by matrix-assisted laser desorption teremia and erysipeloid lesion; iii) absence of difficulty in his movement due to a polymor- ionization time-of-flight (MALDI-TOF) mass endocarditis. MALDI-TOF mass spectrometry phic erythema on the right leg characterized spectrometry (VITEK MS, bioMérieux) using allowed to obtain a rapid identification (within by well-defined and raised borders with a local- the following procedure. An aliquot (2.5 mL) of 4 hours from bottle positivity) of E. rhu- ized edematous skin portion and reddening. the blood culture was transferred in a tube siopathiae. Together with direct antimicrobial Based on laboratory and clinical data (modi- with gel separator (BD Vacutainer® Blood susceptibility testing, this approach could fiedcommercial early warning score = 4), the presence of Collection Tubes, Becton, Dickinson and improve the rate of appropriate therapy for sepsis was suspected.9 Together with other Company, Milan, Italy) and centrifuged at 3500 due to this fastidious interventions (as appropriate for sepsis condi- rpm for 10 minutes. The supernatant was dis- pathogen. tion), two blood cultures were performed and carded and the pellet was inoculated on two Nonsent to the laboratory where they were prompt- blood agar plates incubated at 36°C in O2 and ly incubated in the BacT/ALERT instrument 5% CO2, respectively. After a short term incu- (bioMérieux, Marcy l’Etoile, France). No bio- bation period (4 hours), microbial identifica- Introduction logical samples from leg were sent to the tion was obtained by the VITEK MS directly microbiology laboratory. Therapy with ceftriax- from bacterial growth on agar plates. Erysipelothrix rhusiopathiae is a Gram-posi- one (1 g twice daily) plus azithromycin (500 Microorganisms recovered from agar plates tive bacillus that is infrequently responsible mg daily) was then initiated. The patient were directly applied to VITEK MS target slide for infections in humans. Human disease, recalled that the lesion, then classified as in duplicate (two spots for each isolate) and although rare, can originate from animal or erysipelas, had been present for about two were covered with one microliter of CHCA (α- environmental sources. To this regard, animal months. No contact with animals were report- Cyano-4-hydroxycinnamic acid) matrix. sources are often associated with occupational ed. However, physicians observed that the E. rhusiopathiae was identified according to exposure (butchers, fishermen, fish handlers, patient lived in non-optimal hygienic condi- the observation of Gram-variable rods as veterinarians), with pigs as the most impor- tions. After a 48 h incubation period, an aero- obtained by Gram staining. Next to rapid iden- tant reservoir.1 On the other hand, soil, food bic bottle from blood cultures performed at the tification with VITEK MS, a suspension, adjust- scraps and water contaminated by infected emergency department was flagged positive by ed to a 0.5 McFarland turbidity standard, was animals represent the most common environ- the BacT/ALERT instrument (bioMérieux). created directly from bacterial growth and used mental sources. The organism is widespread Direct microscopic examination based on for direct antimicrobial susceptibility testing and occurs in decomposing organic matter. Gram staining evidenced the presence of by Etest strips (bioMérieux) using the Notably, E. rhusiopathiae can survive in soil for Gram-variable rods. Bacterial identification Mueller-Hinton Fastidious agar (bioMérieux).

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The minimum inhibitory concentrations of 7 case, bacteremia developed subsequently an Of note, although E. rhusiopathiae is usually antibiotics were evaluated, including erysipeloid lesion. highly susceptible to and G, cefotaxime, imipenem, ciprofloxacin, lev- Third, E. rhusiopathiae bacteremia is most cephalosporins, all death patients described in ofloxacin, clindamycin, and . Since commonly associated with severe clinical ill- Table 2 had been treated with such beta-lactam no specific criteria were available for E. rhu- ness and is often complicated with endocardi- antibiotics. Based on data collected from the siopathiae, results were arbitrarily interpreted tis.1 More than one half of patients with sys- recent literature (Table 2), the overall mortali- according to EUCAST criteria and non-species temic infection had predisposing factors such ty rate for bacteremia was 12.5%. Three out of related breakpoints.10 alcohol or drug dependence, immunosuppres- four deaths occurred in patients with endo- As shown in Table 1, antimicrobial agents sion, and chronic liver disease (Table 2). carditis, whereas the remaining occurred in a used for empirical treatment resulted highly Furthermore, our search showed that more patient with sepsis and oropharyngeal cancer. active against the etiological agent isolated than one third of the patients (34.4%) with A previous study reported a mortality rate of from blood. A transesophageal echocardiogra- invasive E. rhusiopathiae infections developed 38% in patients with E. rhusiopathiae endo- phy did not reveal valve vegetation. Ten days endocarditis (Table 2). This rate is much lower carditis.3 In our search the mortality rate for E. after admission, the patient was discharged than that reported by Gorby and Peacock, in rhusiopathiae endocarditis accounted for without fever and in good conditions. The fol- which about 90% of cases of E. rhusiopathiae 27.3% (Table 2). This rate may partly be low-up conducted seven months after dis- bacteremia result in endocarditis.3 However, in explained by the use of vancomycin, often in charge showed good clinical conditions (tak- contrast to these evidences, in our case the combination with gentamicin, in the empirical ing into account his underlying illness). The patient did not present any of these clinical therapy of endocarditis in patients who are erysipelas on the right leg was completely features and no involvement of the endocardi- allergic to penicillin and infected with Gram- cured. um was detected. positive microorganisms.1 With respect to It is noting that bacteremic E. rhusiopathiae available alternative drugs, susceptibility data infection may occur more commonly than for quinolones are very rare in the litera- reports suggest. It may be under-diagnosed ture.4,6,19 In our case, we observed very low MIC Discussion and Conclusions and under-reported because the resemblance values for ciprofloxacin and levofloxacin it bears to other infections and the problems (Table 1), thus suggesting that these drugs This report describes a case of E. rhu- that may be encountered in isolation and iden- couldonly represent a valid therapeutic option, at siopathiae bacteremia without endocarditis in tification of this pathogen. Furthermore, least for patients with known allergy to beta- an immunocompetent patient, successfully Gram-positive rods cultured from blood are lactams, particularly if at risk of infectious treated with ceftriaxone plus azithromycin, often dismissed as difteroids and not fully endocarditis (i.e. patients with heart valve presumably started from a localized skin form. identified. use prosthesis). Similar cases are overall uncommon. Table 2 In our case, bacteremia without involve- The introduction of mass spectrometry in summarizes clinical features of E. rhusiopathi- ment of endocardium was resolved by treat- clinical microbiology laboratory has notably ae invasive case reports, searched in the most ment with ceftriaxone plus azithromycin. To improved identification of microorganisms at recent literature using the PubMed Database this regard, penicillins and cephalosporins are the species level. To our best knowledge, this is (only articles in English have been taken into the first line of choice for treating E. rhu- the first report in which identification of E. account).3-35 siopathiae infections (see also Table 2) while rhusiopathiae has been performed directly With respect to previous reports, our case this pathogen is naturally resistant to van- from positive blood culture bottle by MALDI- presents some particular and uncommon fea- comycin, teicoplanin, daptomycin, gentamicin, TOF mass spectrometry. Identification by mass tures. First, erysipelas is most often caused by netilmicin, polimyxin B, tetracycline and spectrometry and direct antimicrobial suscep- 1 pyogenes or Staphylococcus trimethoprim/sulfamethoxazole. It is worth tibility testing performed on positive blood cul- aureus, less so by group B, C or G streptococ- noting that some of the latter antimicrobial ture can provide results about 24 hours earlier ci.11 For this reason, Erysipelothrix infections commercialagents are commonly used as empirical thera- than routine standard methods. This approach are considered uncommon and especially non- py for treatment of suspected sepsis. Thus, could allow to reduce the duration of empirical occupational cases are very rare. In our case early diagnosis of all forms of E. rhusiopathiae treatment and improve the rate of appropriate infection appears to be essential, especially in the patient lived in non-optimal hygienic con- therapy for bloodstream infections caused by the case of endocarditis. ditions but he had not been in contact with any this fastidious pathogen. animal, so the source of infectionNon could be the soil contaminated by the microorganism and the infection could occur by traumatic penetra- tion in the skin through tiny breaks. Overall, a total of 32 cases (including our case) have been recently reported. Of importance, our Table 1. Susceptibility profile of Erysipelothrix rhusiopathiae blood isolate. search revealed only two other cases associat- Antimicrobial agent MIC (mg/L) Interpretation ed to poor hygienic conditions (in addition to our case), while an exposure to animal Penicillin G 0.004 S sources was mostly present (Table 2). Cefotaxime 0.094 S Second, bacteremic infection, with or with- Imipenem 0.008 S out endocarditis, was previously considered most commonly a primary infection rather Ciprofloxacin 0.094 S than dissemination from localized cutaneous Levofloxacin 0.064 S lesion.1,5,12 In contrast to this assumption, the Clindamycin 0.094 S recent literature shows an increasing rate of Vancomycin 64 - bacteremic infections started from localized Based on EUCAST criteria and non-species related breakpoints.10 No interpretation criteria are available for vancomycin. cutaneous lesion (Table 2). Particularly, in our

[Infectious Disease Reports 2016; 8:6368] [page 9] Case Report

only use as obtained by case reports described in the recent literature.

commercial

Erysipelothrix rhusiopathiae Non F, 43 Skin erythema, bacteremia Systemic lupus erythematosus Contact with uncooked meat CEF, AMX Recovered AMX CEF, meat uncooked with Contact erythematosus lupus Systemic bacteremia erythema, Skin 43 F, NA Psoas , osteomyelitis, bacteremia Cirrhosis, diabetes mellitus NA Surgery, NA Recovered NA Surgery, NA mellitus diabetes Cirrhosis, bacteremia osteomyelitis, abscess, NA Psoas 7 M, 51 Skin erythema, bacteremia, endocarditis, renal failure Chronic alcohol abuser Contact with uncooked meat/fish PEN, Surgery Died Surgery PEN, meat/fish uncooked with Contact abuser alcohol Chronic failure renal endocarditis, bacteremia, erythema, Skin 51M, 25 . 23 M, 53 Skin erythema, bacteremia None Butcher activity PEN, NET Recovered NET PEN, activity Butcher None bacteremia erythema, Skin 53M, . 15 M, 78 Endocarditis, bacteremia Chronic alcohol abuser Uncooked meat consumption PEN, Surgery Recovered Surgery PEN, consumption meat Uncooked abuser alcohol Chronic bacteremia Endocarditis, 78M, F, 18 Skin erythema, bacteremia Systemic lupus erythematosus Occasional contact with animals PEN, AMX Recovered AMX PEN, animals with contact Occasional erythematosus lupus Systemic bacteremia erythema, Skin 18 F, M, 51 Skin erythema, endocarditis, bacteremia Remote history of heroin abuse Poor hygienic condition SAM Recovered SAM condition hygienic Poor abuse heroin of history Remote bacteremia endocarditis, erythema, Skin 51M, et al et M, 44 Skin erythema, endocarditis, bacteremia (3 out of 3) Cirrhosis (case 1); Diabetes mellitus, Farming activity (cases 1 and 2); PEN, CAZ (case 1); Died (case 1); 1); (case Died 1); (case CAZ PEN, 2); 1 and (cases activity Farming mellitus, Diabetes 1); 3) of (case out (3 Cirrhosis bacteremia endocarditis, erythema, Skin 44M, 27 20 et al et 35 . F, neonate Infection contracted during delivery Prematurity, hepatosplenomegaly Poor hygienic condition at birth CTX, AMK Recovered AMK CTX, birthat condition hygienic Poor hepatosplenomegaly Prematurity, delivery during contracted Infection neonate F, F, 52 Bacteremia Bronchitis Contact with uncooked fish PEN Recovered PEN fish uncooked with Contact Bronchitis Bacteremia 52 F, 32 M, 67 Skin erythema, bacteremia Chronic alcohol abuser, cirrhosis Farming activity PENRecovered activity Farming cirrhosis abuser, alcohol Chronic bacteremia erythema, Skin 67M, . 3 13 26 M, 58 Septic shock Diabetes mellitus, myocarditis Fishing activity PEN, CLI, GEN Recovered CLI, PEN, activity Fishing myocarditis mellitus, Diabetes shock Septic 58M, . M, 61 Bacteremia Chronic alcohol abuser, intestinal perforation None CET Recovered CET None perforation intestinal abuser, alcohol Chronic Bacteremia 61M, F, 28 Bacteremia Chronic alcohol abuser, pancreatitis None PEN Recovered PEN None pancreatitis abuser, alcohol Chronic Bacteremia 28 F, M, 79 Skin erythema, pericarditis, bacteremia None Hunting activity PEN Recovered PEN activity Hunting None bacteremia pericarditis, erythema, Skin 79M, 14 M, 53 Skin erythema, septic bursitis, bacteremia Chronic lymphocytic leukemia Farming activity ERY, TOB Recovered TOB ERY, activity Farming leukemia lymphocytic Chronic bacteremia bursitis, septic erythema, Skin 53M, F, 29 Endocarditis, bacteremia Systemic lupus erythematosus None PEN, CEF Recovered CEF PEN, None erythematosus lupus Systemic bacteremia Endocarditis, 29 F, Recovered PEN consumption Fish mellitus Diabetes bacteremia spondylitis, Lumbar 67 F, 18 . M, 70 Skin erythema, endocarditis, bacteremia None Farming activity PEN, TPL, Surgery Died Surgery TPL, PEN, activity Farming None bacteremia endocarditis, erythema, Skin 70M, et al et 21 16 M, 64 Abdominal pain, bacteremia Chronic alcohol abuser, cirrhosis, Uncooked meat consumption PENRecovered consumption meat Uncooked cirrhosis, abuser, alcohol Chronic bacteremia pain, Abdominal 64M, F, 43 , bacteremia Chronic alcohol abuser Gardening activity None Recovered None activity Gardening abuser alcohol Chronic bacteremia Cellulitis, 43 F, Recovered CLO CTX, fish uncooked with Contact disease heart ischemic hypertension, mellitus, Diabetes shock septic Cellulitis, 67 F, . . 30 17 24 et al et 19 5 M, 32 Bacteremia Oropharyngeal cancer Colonization of the oral cavity AMC Died AMC cavity oral the of Colonization cancer Oropharyngeal Bacteremia 32M, . F, 53 Infected trunk, arm and leg ulcer, bacteremia Hepatitis C, cirrhosis Uncooked meat consumption LEV Recovered LEV consumption meat Uncooked cirrhosisC, Hepatitis bacteremia ulcer, leg and arm trunk, Infected 53 F, . . . . 22 4 et al et .33 . 27 . . M, 46 Skin erythema, endocarditis, bacteremia, septic arthritis Chronic alcohol abuser Butcher activity AMC, CLI, Surgery Recovered Surgery CLI, AMC, activity Butcher abuser alcohol arthritis Chronic septic bacteremia, endocarditis, erythema, Skin 46M, F, 63 Meningitis, endocarditis, bacteremia Systemic lupus erythematosus None CRO, VAN, AMP, Surgery Recovered Surgery AMP, VAN, CRO, None erythematosus lupus Systemic bacteremia endocarditis, Meningitis, 63 F, et al et M, 59 Cellulitis, bacteremia None Gardening activity MOX Recovered MOX activity Gardening None bacteremia Cellulitis, 59M, F, 63 Skin erythema, endocarditis, bacteremia, Hepatitis B, chronic alcohol abuser Fishing activity PEN, CRO Recovered CRO PEN, activity Fishing abuser alcohol chronic B, Hepatitis bacteremia, endocarditis, erythema, Skin 63 F, et al et et al et 29 6 34 . M, 54 Skin erythema, bacteremia Chronic lymphocytic leukemia, hepatitis Fish consumption PEN Recovered PEN consumption Fish hepatitis leukemia, lymphocytic Chronic bacteremia erythema, Skin 54M, et al et et al et et al et . et al et 31 et al et . 8 et al et et al et et al et et al et et al et et al et et al et multiple brain infarctions infarctions brain multiple B B bronchopneumonia hypertension, diabetes mellitus mellitus diabetes hypertension, F, 50 nephrotic syndrome (case 2); Dialysis (case 3) None (case 3) CAZ (case 2); Recovered Recovered 2); (case CAZ 3) (case None 3) 2 and (cases 3) (case 3) CLA (case CAZ, Dialysis 2); (case syndrome nephrotic 50 F, 42 F, Surrun Surrun Fernández-Crespo Fernández-Crespo Artz Artz Campbell & Cowan Campbell Totemchokchyakarn Totemchokchyakarn Ko Nandish & Khardori Nandish Schuster Schuster Authors Sex, age Type of infection Underlying illness/risk factors Contact with animals/rural setting Treatment Outcome setting Treatment animals/rural with Contact factors illness/risk Underlying infection of Type age Sex, Authors & Peacock Gorby Cascio Drekonja Birlutiu Ognibene Quabeck & Brady Callon García-Restoy Fakoya Thomas & Khoosal Jones Sheng Romney Mahavanakul Joo Recovered AZI CRO, condition hygienic Poor vasculopathy cerebral Cardiopathy, bacteremia ulcer, arm Infected 74M, report This AMC, Amoxicillin/clavulanate; AMK, Amikacin; AMP, Ampicillin; AMX, Amoxicillin; AZI, Azythromycin; CAZ, Ceftazidime; CEF, Cefazolin; CET, Cephalotin; Ampicillin; CLA, AMX, Clarithromycin; AMC, Amoxicillin; Cefazolin; CLI, Amoxicillin/clavulanate; AZI, CET, Clindamycin; AMK, Azythromycin; CLO, Amikacin; CAZ, Cloxacillin; AMP, Ceftazidime; CRO, Levofloxacin; CEF, Ceftriaxone; Erythromicin; CTX, GEN, Cefotaxime; Gentamicin; ERY, LEV, Netilmicin; PEN, MOX, Penicillin; Moxifloxacin; SAM, VAN, NET, Ampicillin/sulbactam; TPL, Vancomycin; NA, TOB, Teicoplanin; not Tobramycin; available. Shumak Shumak Upapan & Chayakukeeree Upapan Kichloo Kichloo Normann & Kihlstrom Normann Venditti Venditti Townshend Townshend Table 2. Characteristics of bloodstream Table infections caused by

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Erysipelothrix rhusiopathiae intra-abdom- Sathapatayavongs B, Puavilai S. References inal abscess. Int J Infect Dis 2010;14:81-3. Erysipelothrix rhusiopathiae septicemia 13. Townshend RH, Jephcott AE, Yekta MH. in systemic lupus erythematosus. Int J 1. Wang Q, Chang BJ, Riley TV. Erysipelothrix septicaemia without endo- Dermatol 1996;35:818-20. Erysipelothrix rhusiopathiae. Vet carditis. Br Med J 1973;1:464. 26. Jones N, Khoosal M. Erysipelothrix rhu- 14. Ognibene FP, Cunnion RE, Gill V, et al. Microbiol 2010;140:405-17. siopathiae septicemia in a neonate. Clin 2. Veraldi S, Girgenti V, Dassoni F, Gianotti R. Erysipelothrix rhusiopathiae bacteremia Infect Dis 1997;24:511. Erysipeloid: a review. Clin Exp Dermatol presenting as septic shock. Am J Med 27. Nandish S, Khardori N. Valvular and 2009;34:859-62. 1985;78:861-4. 3. Gorby GL, Peacock JE Jr. Erysipelothrix 15. Normann B, Kihlström E. 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