bacteraemia caused by actinobaculum schaalii: an overlooked pathogen?

4
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) Scandinavian Journal of Infectious Diseases, 2014; 46: 605–608 ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2014.913306 SHORT COMMUNICATION Bacteraemia caused by Actinobaculum schaalii: An overlooked pathogen? JOHANNA SANDLUND 1,2 , MARTIN GLIMÅKER 1,3 , ANITA SVAHN 2,4 & ANNELIE BRAUNER 2,4 From the 1 Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institute, 2 Department of Clinical Microbiology, Karolinska University Hospital, 3 Department of Infectious Diseases, Karolinska University Hospital, and 4 Department 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 infec- tions (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, facul- tative anaerobic coccoid rod that grows slowly, preferably in 5% CO 2 or an anaerobic atmosphere [1,2,8]. The tiny grey colonies show weak beta- haemolysis on blood agar and are catalase-negative [2,8]. A. schaalii is easily overgrown by other bacte- ria, and is presumably often overlooked or consid- ered 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 stan- dard 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 Scand J Infect Dis Downloaded from informahealthcare.com by Dicle Univ. on 11/10/14 For personal use only.

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Page 1: Bacteraemia caused by Actinobaculum schaalii: An overlooked pathogen?

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 )

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

ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa HealthcareDOI: 10.3109/00365548.2014.913306

SHORT COMMUNICATION

Bacteraemia caused by Actinobaculum schaalii: An overlooked pathogen?

JOHANNA SANDLUND 1,2 , MARTIN GLIM Å KER 1,3 , ANITA SVAHN 2,4 & ANNELIE BRAUNER 2,4

From the 1 Infectious Diseases Unit, Department of Medicine Solna, Karolinska Institute, 2 Department of Clinical Microbiology, Karolinska University Hospital, 3 Department of Infectious Diseases, Karolinska University Hospital, and 4 Department of Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden

Abstract Actinobaculum schaalii is a uropathogen resistant to ciprofl oxacin and trimethoprim – sulfamethoxazole. It requires a long culture time and specifi c conditions, and is therefore easily overgrown by other bacteria and regarded as part of the normal bacterial fl ora. 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 infec-tions (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 ciprofl oxacin and trimethoprim – sulfamethoxazole [1,6,7].

A. schaalii is a Gram-positive, non-motile, facul-tative anaerobic coccoid rod that grows slowly, preferably in 5% CO 2 or an anaerobic atmosphere [1,2,8]. The tiny grey colonies show weak beta-haemolysis on blood agar and are catalase-negative [2,8]. A. schaalii is easily overgrown by other bacte-ria, and is presumably often overlooked or consid-ered 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 identifi ed 17 cases of A. schaalii bacteraemia. Cultures were performed using stan-dard laboratory procedures and A. schaalii isolates were verifi ed 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 μ M/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

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606 J. Sandlund et al.

the nitrite test was negative. Moderate anaemia, thrombocytosis, and hypoalbuminaemia, and an ini-tially severe hypercalcaemia, were noted. Due to a blood leukocyte count of 26.5 � 10 9 /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 μ M/l, leukocyte count to 15.6 � 10 9 /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 nor-mal urethral fl ora. Amoxicillin 500 mg was given for another 10 days and at follow-up 6 weeks after dis-charge 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 cul-tures 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 ciprofl oxacin before sensitivity testing results were available (Table I). Among the tested isolates, the majority were resistant to ciprofl oxacin, 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% CO 2 and anaerobic atmosphere is only performed when clinicians specifi cally 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 fl ora 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 cul-tures 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 con-taminants. Awareness of this pathogen therefore needs to be raised.

Since A. schaalii is resistant to ciprofl oxacin and trimethoprim – sulfamethoxazole [1,6,7], there is a substantial risk of treatment failure in UTI. Antibi-otic treatment for several weeks has been recom-mended, 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 suscepti-bility to these compounds. As expected, a majority were resistant to ciprofl oxacin and trimethoprim – sulfamethoxazole, highlighting the need for attention when treating patients with UTIs.

In conclusion, we have demonstrated that A. schaalii has signifi cant invasive potential. We empha-size the need for special attention from both clini-cians and microbiologists in order not to overlook this pathogen. In patients with UTI or urosepticae-mia of unknown aetiology or with treatment failure,

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Page 3: Bacteraemia caused by Actinobaculum schaalii: An overlooked pathogen?

Bacteraemia caused by Actinobaculum schaalii 607

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608 J. Sandlund et al.

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 proce-dures allowing growth of A. schaalii should be per-formed. Further studies are needed to identify risk factors and clinical manifestations, and to determine the optimal treatment duration.

Acknowledgements

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 confl icts of interest. The authors alone are respon-sible for the content and writing of the paper.

References

Reinhard M , Prag J , Kemp M , Andresen K , Klemmensen B , [1] H ø jlyng N , et al . Ten cases of Actinobaculum schaalii infec-tion: clinical relevance, bacterial identifi cation, and antibiotic susceptibility . J Clin Microbiol 2005 ; 43 : 5305 – 8 .

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

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