F. tularensis during pregnancy poses a risk to pregnant women and the fetus. Intrauterine death caused by F. tularensis is well described in animals, and discussed in humans [3, 4]. Most frequently used regimens during pregnancy include aminoglycosides or aminoglycoside and quinolone combinations [5, 6]. Both options are potentially toxic during pregnancy and should be avoided if possible [2]. The effectiveness of better tolerable agents, such as macrolides, is discussed in vitro, but differs dependent on the subspecies. Whereas, F. tularensis subspecies tularensis (type A strain) (minimum inhibitory concentration (MIC) 0.125–2 mg/L) and F. tularensis subspecies holarctica (type B strain) biovar I (MIC 0.064–2 mg/L) are generally susceptible to macrolides, F. tularensis subspecies holarctica biovar II is generally not susceptible (MIC > 256 mg/L) [7]. The erythromycin resistance in F. tularensis can be linked to a gene mutation, which was only found in the phylogenetic group B12 [8]. Phylogeography analysis of F. tularensis in Europe demonstrated that most infections in Central and Eastern Europe are caused by the macrolide-resistant group, whereas F. tularensis infections in Western Europe are mainly caused by the macrolide-susceptible group [9].

Previously, one pregnant patient with tularemia caused by a F. tularensis type A strain in North America, as well as one patient with tularemia caused by F. tularensis subsp. holarctica biovar 1 strain in France, was successfully treated by azithromycin [10, 11]. In another report in France, two other pregnant tularemia patients were successfully treated with josamycin or azithromycin, but only improved after surgical removal of suppurated lymph node. F. tularensis subspecies was not specified in this report [12].

In Austria, phylogenetic analysis demonstrated that most infections are caused by a macrolide-resistant subspecies (F. tularensis subsp. holarctica clade B.13) [9]. We could not determine the subspecies of F. tularensis in this patient, because it did not grow in culture and therefore insufficient material for classification was available. However, just after the first treatment cycle, the patient experienced fever as well as temporary increase of swelling of the lymph nodes after the first dose of azithromycin, which was surprising and might have indicated some kind of Jarisch–Herxheimer like reaction due to the rapid destruction of bacteria [13]. This treatment related inflammatory response as well as the rapid improvement afterward strengthened our decision to continue the treatment with azithromycin.

We preferred intravenous azithromycin over other macrolides due to the longer half-life, higher volume of distribution, and interstitial fluid-plasma concentrations, allowing outpatient parenteral antibiotic treatment [14]. To achieve higher tissue concentrations, azithromycin was administered intravenously, and repeated over 3 days. In a retrospective analysis, 15% of the tularemia patients treated with doxycycline (≥ 14 days) experienced treatment failure [15]. Hence, we decided to continue treatment four times over a period of 4 weeks to prevent relapse and subsequent surgery. To ensure response to treatment and to allow adjustment of treatment as early as possible, the patient was monitored closely. Clinical examinations and ultrasound assessments demonstrated a rapid and sustained response. She later gave birth to her child without complications.

Overall, this case report supports azithromycin as a therapeutic option for tularemia in patients during pregnancy. Pretreatment evaluation of F. tularensis subspecies may nevertheless be important, especially in areas with a high prevalence of azithromycin-resistant subspecies.