Scandinavian Journal of Infectious Diseases, 2014; 46: 605–608

SHORT COMMUNICATION

Bacteraemia caused by Actinobaculum schaalii: An overlooked pathogen?

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JOHANNA SANDLUND1,2, MARTIN GLIMÅKER1,3, ANITA SVAHN2,4 & ANNELIE BRAUNER2,4 From the 1Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institute, 2Department of Clinical Microbiology, Karolinska University Hospital, 3Department of Infectious Diseases, Karolinska University Hospital, and 4Department of Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden

Abstract Actinobaculum schaalii is a uropathogen resistant to ciprofloxacin and trimethoprim–sulfamethoxazole. It requires a long culture time and specific conditions, and is therefore easily overgrown by other bacteria and regarded as part of the normal bacterial flora. We review 17 cases of A. schaalii bacteraemia, demonstrating its invasive potential. A. schaalii should always be ruled out as causative agent in patients with urinary tract infection or urosepticaemia with treatment failure.

Keywords: Actinobaculum schaalii, bacteraemia, urosepticaemia, urinary tract infection

Introduction Actinobaculum schaalii causes urinary tract infections (UTI), primarily in elderly patients and in patients with urological risk factors [1–5]. Although sensitive to beta-lactams and the majority of other antibiotics, A. schaalii is resistant to ciprofloxacin and trimethoprim–sulfamethoxazole [1,6,7]. A. schaalii is a Gram-positive, non-motile, facultative anaerobic coccoid rod that grows slowly, preferably in 5% CO2 or an anaerobic atmosphere [1,2,8]. The tiny grey colonies show weak betahaemolysis on blood agar and are catalase-negative [2,8]. A. schaalii is easily overgrown by other bacteria, and is presumably often overlooked or considered a contaminant [3,9]. A. schaalii has been seen in single cases of other infections, such as spondylitis, and has also been isolated from blood, but little is known about its systemic pathogenic potential.

Methods Between October 2009 and August 2013, the Department of Clinical Microbiology, Karolinska

University Hospital identified 17 cases of A. schaalii bacteraemia. Cultures were performed using standard laboratory procedures and A. schaalii isolates were verified with 16S rRNA gene sequencing and catalase. Antibiotic sensitivity testing was performed with the Etest (AB Biodisk, Solna, Sweden). The study was approved by the regional ethics committee (Dnr 2014/301-31/2). Case report A 62-y-old man was admitted after acute onset of severe urinary problems, malaise, and diarrhoea. Trans-urethral microwave therapy (TUMT) had been performed for benign prostate hyperplasia 2 months earlier, and since then he had required the intermittent use of a urinary catheter. On admission, a palpable resistance corresponding to the urinary bladder was found, containing more than 1 l of urine. The patient’s body temperature was 37.8°C and his P-creatinine was 1100 μM/l, indicating severe kidney damage due to post-renal blockage. A suprapubic catheter was applied; the urine contained increased levels of erythrocytes, leukocytes, and protein, but

Correspondence: J. Sandlund, Division of Clinical Microbiology, Karolinska University Hospital and Karolinska Institute, SE-17176 Stockholm, Sweden. E-mail: [email protected], [email protected] (Received 12 October 2013 ; accepted 31 March 2014 ) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2014.913306

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the nitrite test was negative. Moderate anaemia, thrombocytosis, and hypoalbuminaemia, and an initially severe hypercalcaemia, were noted. Due to a blood leukocyte count of 26.5 ⫻ 109/l and C-reactive protein (CRP) of 364 mg/l, a UTI was suspected, and treatment with cefotaxime was initiated. The patient improved gradually and was discharged after 5 days, when the P-creatinine level had decreased to 304 μM/l, leukocyte count to 15.6 ⫻ 109/l, and CRP to 108 mg/l. A. schaalii, sensitive to cefotaxime and amoxicillin, was later isolated in blood culture, whereas the urine culture showed growth of the normal urethral flora. Amoxicillin 500 mg was given for another 10 days and at follow-up 6 weeks after discharge the patient had recovered and the suprapubic catheter was removed.

Results Among the 17 patients with A. schaalii bacteraemia, 14 were men and the mean age was 75 y (median 79, range 17–92 years). Fifteen patients (88%) had symptoms of UTI, 13 (77%) had urinary catheter support, 1 patient had a urethral stricture, and 2 patients presented with malignancies. Blood cultures from 6 patients revealed growth of concomitant bacteria (Table I). Out of 22 pairs of blood culture bottles, 14 (64%) aerobic bottles and 19 (86%) anaerobic bottles showed growth, this after a mean time of 52.8 h (range 29.0–70.8 h) and 34.6 h (range 14.9–53.8 h), respectively. Urine culture was performed for 15 patients. Interestingly, A. schaalii was not isolated from any of the urine samples. When bacterial growth was detected in the blood cultures, antibiotic treatment had already been initiated in 15 patients. Eleven patients were treated with cefotaxime. For 3 of these patients, therapy was changed to ciprofloxacin before sensitivity testing results were available (Table I). Among the tested isolates, the majority were resistant to ciprofloxacin, and all were resistant to trimethoprim–sulfamethoxazole, while all tested strains were sensitive to benzylpenicillin, cefotaxime, and piperacillin–tazobactam.

Discussion The majority of patients in the current study were men of relatively old mean age with symptoms indicating that the genitourinary tract was the port of entry. Underlying conditions and risk factors, such as long-term urinary catheter usage, anatomical disorders, and genitourinary cancer, were observed in 13 of the 17 patients. Why A. schaalii bacteraemia affects mainly men is unclear, but it has been

suggested that prostatic hyperplasia could be a risk factor [5]. Considering the age of the patients included in this study, the prevalence of prostatic hyperplasia is presumably high. Also, 2 of the 3 women with A. schaalii bacteraemia had risk factors including nephrostomy and urinary catheters. None of the patients in the current study had growth of A. schaalii in urine culture. Since urine culture in 5% CO2 and anaerobic atmosphere is only performed when clinicians specifically suspect A. schaalii infection and request it, this outcome is not a surprise. Morphologically, A. schaalii resembles Corynebacterium spp. and Lactobacillus spp., increasing the risk that it is considered a contaminant [3,5,9], especially in standard cultures. Additionally, the challenges when culturing A. schaalii often lead to overgrowth by other bacteria and mixed infections [9]. Analyzing 252 routine urine samples for the presence of A. schaalii by a real-time quantitative PCR, Bank et al. found that 16% were positive for A. schaalii [3], clearly indicating that A. schaalii is an often overlooked pathogen in urine samples. A mixed bacterial flora was detected in the blood cultures of 6 patients. Four had simultaneous growth of either Corynebacterium sp. or slow-growing anaerobic Gram-positive round cocci. Considering the similar morphological features of A. schaalii, there is a risk of misinterpretation. The Department of Clinical Microbiology at Karolinska University Hospital receives approximately 80,000 blood cultures from 30,000 patients annually. Of these, 12– 13% are positive, with growth of bacteria or fungi. Considering this high volume, it is noteworthy that only a few isolates, blood and urine included, showed growth of A. schaalii. It cannot be ruled out that some isolates have wrongly been considered contaminants. Awareness of this pathogen therefore needs to be raised. Since A. schaalii is resistant to ciprofloxacin and trimethoprim–sulfamethoxazole [1,6,7], there is a substantial risk of treatment failure in UTI. Antibiotic treatment for several weeks has been recommended, which also has to be taken into consideration [2,5,6,7]. A. schaalii is susceptible to beta-lactams. In our study, 15 patients (88%) were treated with beta-lactams, and the isolates showed high susceptibility to these compounds. As expected, a majority were resistant to ciprofloxacin and trimethoprim– sulfamethoxazole, highlighting the need for attention when treating patients with UTIs. In conclusion, we have demonstrated that A. schaalii has significant invasive potential. We emphasize the need for special attention from both clinicians and microbiologists in order not to overlook this pathogen. In patients with UTI or urosepticaemia of unknown aetiology or with treatment failure,

M

M

M

M

M

F

F

M

M

M

M

M

M

M

M F M

82

73

81

71

17

83

77

57

79

77

74

89

92

88

82 84 62

Urosepsis Urosepsis Urinary retention

Unknown

Unknown

UTI

Urinary retention Urosepsis

Fever, nausea Unknown

Unknown

Respiratory infection Urosepsis

Urosepsis

UTI

Respiratory infection

Urosepsis Corynebacterium sp (1/1)

0

Concomitant flora, blood (No. of bottles)

Urinary catheter Unknown Urinary catheter

Suprapubic urinary catheter Urinary catheter

Prostate cancer, urinary catheter Unknown

Urinary catheter

Oesophageal cancer Unknown

Gram-positive cocci, anaerobic (1/2) 0 0 0

0

0

0

0

Streptococcus sp. (1/4) 0

Permanent urinary 0 catheter Urinary catheter, Staphylococcus PD epidermidis (1/4) Urethral stricture Corynebacterium sp. (4/4) Nephrostomy Prevotella sp. (2/4) ⫹ alpha-haemolytic streptococci (4/4) Urinary catheter 0

Urinary catheter

Urinary catheter

Co-morbidity/ risk factors

No

Yes (negative) Yes (urethral flora) Yes (negative)

Yes (negative)

Yes (Aerococcus sanguinicola) Yes (mixed flora)

No

Yes (urethral flora)

Yes (negative)

NPH (negative) No No

No

No

No

No

No

NPH (negative)

Yes (Gram-positive NPH (Moraxella catarrhalis) mixed flora) Yes (urethral flora) NPH (respiratory flora)

No

CIP ® CTX ® CIP PTZ ⫹ ERY

Treatmenta

CTX ® CIP CTX ® CIP CTX

CTX

Urology Infectious disease Urology

Neurology

CTX ® CDX Urology

Unknown

Unknown

CTX

Palliative home care Urology

Emergency department Urology

CEF ⫹ GEN

PTZ

Emergency department Oncology

Emergency department General surgery

Emergency department Neurology

Emergency department

Urology

Referring department

CTX

CTX

CIP

CTX

NPH (Moraxella catarrhalis ⫹ Haemophilus influenzae); and tracheal secretion (respiratory flora) NPH (respiratory flora) CTX

No

Other cultures taken (finding)

Yes (Gram-positive NPH (respiratory flora) mixed flora) Yes (negative) NPH (respiratory flora)

Yes (urethral flora)

Yes (Klebsiella pneumoniae)

Yes (urethral flora)

Urine culture taken (finding)

Yes Yes Yes

Yes

Yes

Yes

Yes

Yes

No

No

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Urinary complicationsb

M, male; F, female; NPH, nasopharynx; UTI, urinary tract infection; PD, Parkinson’s disease; CIP, ciprofloxacin; CTX, cefotaxime; PTZ, piperacillin–tazobactam; ERY, erythromycin; GEN, gentamicin; CDX, cefadroxil; CEF, ceftazidime. aAt the time point when a blood culture bottle is positive and initial Gram stain identification is made, this finding is communicated by the microbiologist to the clinician, and the presented information on antibiotic treatment was given. bIncluding symptoms from the urinary tract, referrals from the urology department, and co-morbidities and risk factors such as urinary catheter, nephrostomy, and prostate cancer.

Sex

Age

Clinical presentation

Table I. Clinical and microbiological characteristics of 17 patients with Actinobaculum schaalii bacteraemia.

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as well as in patients with co-morbidities and known risk factors, A. schaalii should always be ruled out as a causative agent. Considering the potential risk for diagnostic misinterpretation, careful culture procedures allowing growth of A. schaalii should be performed. Further studies are needed to identify risk factors and clinical manifestations, and to determine the optimal treatment duration. Acknowledgements

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The authors wish to thank Peggy Bergquist at the Department of Clinical Microbiology, Karolinska University Hospital, for skilful technical assistance. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

References [1] Reinhard M, Prag J, Kemp M, Andresen K, Klemmensen B, Højlyng N, et al. Ten cases of Actinobaculum schaalii infection: clinical relevance, bacterial identification, and antibiotic susceptibility. J Clin Microbiol 2005;43:5305–8.

[2] Nielsen HL, Søby KM, Christensen JJ, Prag J. Actinobaculum schaalii: a common cause of urinary tract infection in the elderly population. Bacteriological and clinical characteristics. Scand J Infect Dis 2010;42:43–7. [3] Bank S, Jensen A, Hansen TM, Søby KM, Prag J. Actinobaculum schaalii, a common uropathogen in elderly patients, Denmark. Emerg Infect Dis 2010;16:76–80. [4] Bank S, Hansen TM, Søby KM, Lund L, Prag J. Actinobaculum schaalii in urological patients, screened with realtime polymerase chain reaction. Scand J Urol Nephrol 2011; 45:406–10. [5] Beguelin C, Genne D, Varca A, Tritten ML, Siegrist HH, Jaton K, et al. Actinobaculum schaalii: clinical observation of 20 cases. Clin Microbiol Infect 2011;17:1027–31. [6] Cattoir V, Varca A, Greub G, Prod’hom G, Legrand P, Lienhard R. In vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents and molecular analysis of fluoroquinolone resistance. J Antimicrob Chemother 2010;65:2514–7. [7] Cattoir V. Actinobaculum schaalii: review of an emerging uropathogen. J Infect 2012;64:260–7. [8] Lawson PA, Falsen E, Akervall E, Vandamme P, Collins MD. Characterization of some Actinomyces-like isolates from human clinical specimens: reclassification of Actinomyces suis [Soltys and Spratling] as Actinobaculum suis comb. nov. and description of Actinobaculum schaalii sp. nov. Int J Syst Bacteriol 1997;47:899–903. [9] Tschudin-Sutter S, Frei R, Weisser M, Goldenberger D, Widmer AF. Actinobaculum schaalii—invasive pathogen or innocent bystander? A retrospective observational study. BMC Infect Dis 2011;11:289.

Bacteraemia caused by Actinobaculum schaalii: An overlooked pathogen?

Actinobaculum schaalii is a uropathogen resistant to ciprofloxacin and trimethoprim-sulfamethoxazole. It requires a long culture time and specific con...
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