Introduction
The genus
Actinobaculum was first described in 1997, when it was separated from
Actinomyces [
1,
2]. Several species belonging to
Actinobaculum were reclassified in 2015 and they were proposed to constitute a novel genus,
Actinotignum [
2]. This genus now comprises three species:
Actinotignum schaalii,
Actinotignum sanguinis, and
Actinotignum urinale [
2]. These bacteria are small facultative anaerobic Gram-positive rods that are non-motile and catalase-negative [
1]. They grow slowly and preferably under anaerobic or CO
2 conditions, and are easily overgrown by other bacteria [
3].
Actinotignum species are probably part of the normal urogenital flora [
4] and have been associated with urinary tract infections [
5,
6]. They are, however, most likely under-diagnosed in urine cultures, since most clinical microbiological laboratories routinely only use aerobic growth conditions. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) appears to be a useful method for correct species determination of these bacteria [
3].
Actinotignum schaalii has been associated with urinary tract infections [
6,
7] but can also cause invasive infections, such as Fournier’s gangrene, urinary bladder necrosis, bacteremia, and endocarditis [
8‐
11]. The characteristics of infections with
A. schaalii have been described in two recent reviews [
5,
12]. However, only a few studies have addressed the clinical presentation of
Actinotignum bacteremia. In a study from Denmark, 98 patients with
A. schaalii bacteremia were identified between 2011 and 2014, but the clinical presentation was only described for ten patients [
8]. These had a median age of 79 years, 70% were male, and 50% had predisposing urogenital conditions. In a Swedish study, 17 cases of
A. schaalii bacteremia were identified retrospectively and patients were shown to typically be older males with underlying urogenital risk factors [
13]. Similar results have been indicated in a case series from Spain [
14], as well as in reports of single cases and smaller case-series [
7,
15‐
20]. Given the low number of cases reported, the prognosis of
Actinotignum bacteremia is not known.
In published cases, the preferred treatment of
A. schaalii bacteremia has been with β-lactams to which the bacterium has low minimum inhibitory concentration (MIC) values. However, since bacteremia typically has a urinary tract focus, there is a risk that empiric treatment will be given with antibiotics such as trimethoprim–sulfamethoxazole or ciprofloxacin, to which the bacterium is resistant in vitro [
16,
19,
21]. The duration of the treatment is still uncertain but there have been failures after 1 week of ampicillin treatment [
6,
19], which indicates that longer treatment periods may be needed. In this retrospective study, we present the incidence, clinical presentation, and prognosis of
Actinotignum bacteremia in southern Sweden.
Discussion
The number of reported cases of
Actinobaculum/
Actinotignum bacteremia has been very low, possibly due to the relatively recent identification of the species and missed identification in the microbiological laboratories. With MALDI-TOF MS as the primary species identification method and an increasing number of older persons with urinary tract morbidity,
Actinotignum infections will likely be more frequently encountered. We report an incidence of
Actinotignum bacteremia of 11 cases per million inhabitants per year, which is higher than what is suggested by a recent Danish study [
8]. Our results confirm previous studies showing that patients affected by the condition are typically older males with underlying urinary tract conditions [
8,
13,
14]. From our case series, which is the largest one to date, the prognosis of
Actinotignum bacteremia can be assessed. We report a relatively high mortality (16%), which is likely related to the advanced age and co-morbidity of the patients. Some of the deceased patients had polymicrobial bacteremia and the exact contribution of
A. schaalii to the outcome is difficult to determine.
Actinotignum schaalii is the most commonly isolated
Actinotignum species both in our study and in previous reports [
6‐
8,
13]. We identified one case of
A. sanguinis and two cases of
A. urinale bacteremia. However, MALDI-TOF MS was unable to reliably identify all isolates to the species level. Sequencing of the 16S rRNA gene proved to have a limited ability to separate
A. schaalii from
A. sanguinis and, therefore, some isolates could not be identified to the species level.
There are many similarities between
A. schaalii and
Aerococcus urinae [
27]. Both species probably colonize the urinary tract and they have been difficult to correctly identify in the past. They cause invasive infections mostly in older males with underlying urogenital conditions, and are resistant to antibiotics commonly used to treat urinary infections. In fact,
Actinotignum species and
Aerococcus species have been isolated together from blood previously [
18,
23] and, in our material,
Aerococcus was the most common finding in polymicrobial
Actinotignum bacteremia. Our previous description of
Aerococcus bacteremia and the present description of
Actinotignum bacteremia, however show some differences [
23,
28,
29]. The mortality is higher in
Actinotignum bacteremia as compared to
Aerococcus bacteremia (16 vs. 8%) [
18,
23]. This could either be due to specific bacterial virulence factors expressed by
Actinotignum or also be due to host factors such as more advanced underlying conditions. Another difference is that
Actinotignum species rarely seem to cause infective endocarditis as opposed to
Aerococcus species, which cause endocarditis in a significant proportion of cases of bacteremia [
23,
30,
31]. In our series, no case of endocarditis was found and only a single case of endocarditis caused by
Actinotignum has been reported previously [
9].
Only in one of the patients was A. schaalii isolated from urine. This is most likely due to routine practices in the clinical microbiology laboratory, which are unfavorable for the detection of Actinotignum species. Our findings, however, suggest that the urinary tract was the focus of the bacteremia in a majority of the cases. Many patients had underlying urological conditions and presented with signs and symptoms from the urinary tract. The patients with polymicrobial bacteremia had other typical uropathogens in their blood and urine cultures, such as Aerococcus species, E. coli, and E. faecalis, which also suggest a urinary tract focus. The patients who received a clinical diagnosis of pneumonia did not fulfill criteria necessary for that diagnosis and most of them likely had a urinary tract focus of infection.
There are no clinical break points established for
Actinotignum species. However, from our results on antimicrobial susceptibility testing, β-lactams and vancomycin seem like feasible treatment options. Trimethoprim and ciprofloxacin display high MIC values and should be avoided. Previous studies have reported relapse of
A. schaalii infections, which has led to suggestions of prolonged treatment [
6,
19]. The median length of antibiotic treatment in this series was 2 weeks and, to our knowledge, there were no treatment failures. One patient had two episodes of
A. schaalii bacteremia during a 6-month period, and this represented a recurrent infection rather than a treatment failure.
In conclusion, our results demonstrate that Actinotignum bacteremia is more common than previously thought and that it represents a condition with a significant fatality in elderly patients with underlying conditions. The urinary tract should be suspected as the primary focus of infection but, unfortunately, Actinotignum species seldom grow in ordinary urine culture conditions.