Rhodococcus defluvii pneumonia: first reported case in humans.

In 2014, Kämpfer et al.[1] described a new Rhodococcus strain Ca11T isolated from a wastewater bioreactor in Germany. Strain Ca11T clearly differed from the most closely related species of the genus Rhodococcus; therefore, it was proposed as the representative type strain of Rhodococcus defluvii species nova, enriching the list of over 40 species classified under this genus. Although Rhodococcus species are generally considered to have low pathogenicity, they cause diseases in animals, plants and humans, especially people living with HIV and people undergoing immunosuppressive therapy, causing a wide range of manifestations: from subacute pneumonia to life-threatening disseminated disease [2]. Most human infections have been caused by Rhodococcus equi, and only rare cases were reported for other species such as Rhodococcus rhodochrous, Rhodococcus fascians and Rhodococcus erythropolis[3]. To the best of our knowledge, no human cases of R. defluvii have so far been described in literature. With this letter, we report the isolation of a macrolide-resistant R. defluvii strain in the bronchoalveolar lavage (BAL) of a 42-year-old white man. He was employed in the steel industry and, in his spare time, he worked on his family farm, which housed pigs, cows and poultry. He was admitted because of fever and cough in a recently diagnosed HIV-1 infection. His medical history was unremarkable except for reported unprotected intercourses and a previously treated Neisseria gonorrhoea infection. At admission, he was feverish with crackles in the lower lobe of his left lung. Blood exams revealed lymphopenia (400/μl, normal value 1000–4800), elevated C-reactive protein (131 mg/l, normal value <6), 34 CD4+ cells/μl (8.6%, CD4+/CD8+ 0.12) and HIV-RNA 200 000 copies/ml. The computed tomography (CT) scan characterized a left lower lobe consolidation with an excavated fluid-filled cavity (Fig. 1). Serum cryptococcal antigen and Xpert MTB/RIF on three sputum samples were negative. A BAL was performed, then an empirical therapy with ceftriaxone was started. BAL cultures turned positive for Gram-positive, nonalcohol/acid-resistant cocci colonies; the strain identification was not possible with standard methods, being generically labeled as Corynebacterium spp. To exclude the possibility of a contamination, a second BAL was carried out with the same result. Therefore, to ensure protection against hard-to-identify bacteria, meropenem and azithromycin were started, leading to initial improvement of symptoms.Fig. 1: Radiological findings of necrotizing pneumonia by Rhodococcus defluvii.(a) Computed tomography scan demonstrated a left lower lobe consolidation with a fluid-filled cavity and initial excavation in its context. (b) Follow-up computed tomography scan showed a significant decrease in consolidation volume and disappearance of the excavation in its context.A 16S rRNA sequencing was performed on colonies grown on a sheep blood agar plate [4]. The isolate, identified as R. defluvii, had a 100% homology with a GenBank sequence (JPOC0100058). The antimicrobial susceptibility testing documented resistance to penicillin G, ceftriaxone and azithromycin, whereas the strain was susceptible to meropenem, linezolid, gentamicin, cotrimoxazole, amikacin, rifampin and tetracycline. Hence, the treatment was modified to oral linezolid in combination with meropenem, leading to remission of symptoms. Moreover, few days after admission, the patient was started on a HAART and, in 4 weeks, he exhibited a remarkable recovery of CD4+ cells (193 cells/μl, 32.2%, CD4+/CD8+ 0.92) and a significant decay of HIV-RNA (3370 copies/ml). After 3 weeks, the treatment was switched to an entirely oral regimen of linezolid and cotrimoxazole. A CT scan was performed after 10 weeks of effective treatment, demonstrating significant decrease in consolidation volume and disappearance of the excavation in its context (Fig. 1). Sangal et al.[5] sequenced the whole genome of R. defluvii strain Ca11T, and the comparative genomic and phylogenetic analyses confirmed its close relatedness with R. equi strains, which share more than 80% of the gene content. The R. equi virulence plasmid is absent, though most of the chromosomal virulence-associated genes are present in R. defluvii Ca11T[5]. These data suggest that, although R. defluvii is an environmental organism, it is closely related to R. equi, and that it may similarly have the potential to cause disease in human hosts. In case of unclear identification, the identity of the isolate as R. defluvii or R. equi needs to be confirmed by whole genome sequencing phylogenomic analysis. Resistance to macrolides and rifampin in R. equi is increasing, with isolates resistant to macrolides and rifampin being cultured from up to 40% of infected foals at some farms [6]. In our case, it is not possible to exclude that the livestock was unwittingly fed with antibiotics. In the case we are describing, antibiotic susceptibility testing drove the adjustment of antimicrobial therapy towards a macrolide-resistant R. defluvii strain. Despite the length of treatment in Rhodococci-related pneumonia is not standardized, prolonged treatment with two antibiotics until host immune recovery has generally been recommended due to the high risk of recurrence. In our opinion, as the amount of immunosuppressed patients is expected to increases in the future, further cases of infection with non-equi Rhodococcus species such as R. defluvii and R. erythropolis may occur. Prompt communication of clinical suspicion to a microbiologist is critical to diagnose this potentially life-threatening opportunistic infections and promote antimicrobial susceptibility testing-driven therapy. Treatment duration could be guided by the clinical features and immunological recovery of the host until complete resolution of the pneumonia. Acknowledgements Consent for publication We obtained written informed consent for publication of clinical details and clinical pictures from the patient. The written informed consent is available upon request. Author contributions D.C., N.R., A.M., G.T. and M.G. gave substantial contributions to the conception and design, or acquisition of data, or analysis and interpretation of data. D.C., N.R., A.M., G.T. and M.G. have been involved in drafting the article and/or with critical revision. D.C., A.M., M.G., N.R. and G.T. took care of the patient. P.C. and R.P. took care of patient's specimens. D.C., N.R., G.T., A.C. and M.G. supervised the creation of the article. All authors have read and approved the final article. Conflicts of interest There are no conflicts of interest.