A 61-year-old woman with diffuse large B cell lymphoma underwent eight cycles of first-line plus three cycles of second-line chemotherapy; both first- and second-line regimens included rituximab. As after chemotherapy she experienced disease progression, she underwent chimeric antigen receptor T cell therapy (CAR-T with Yescarta®) on 11/08/2021 (day 0). Of note, as comorbidity she had severe osteoporosis complicated by multiple vertebral fractures.

On day + 20, the patient complained about lumbar pain, first ascribed to multiple already known fractures. At that time, her immunoglobulin level was low [IgG 2.200 g/L (normal value 8.000–17.000), IgA 0.225 g/L (normal value 0.700–4.000), IgM 0.031 g/L (normal value 0.400–2.300)] as a consequence of prolonged rituximab therapy.

On day + 30, she underwent fluorodeoxyglucose–positron emission tomography (FDG-PET) study (Fig. 1), which showed complete metabolic response in sites of lymph nodal disease but revealed elevated high tracer uptake at the first (L1) and second (L2) lumbar vertebrae [standardized uptake value (SUV) max 16.2]. On day + 42, lumbar magnetic resonance imaging (MRI) was performed, showing structural disruption by pathological tissue at multiple levels and suspected pathological fracture at L1–L2. On day + 49, vertebral biopsy and vertebroplasty were performed. Histological examination revealed inflammation and excluded neoplastic process. Biopsy culture grew M. hominis on sheep blood agar plates and identification was performed with matrix-assisted laser desorption–ionization time of flight (MALDI-TOF) after 2 days of incubation at 37 °C in aerobic conditions. Considering histological characteristics and microbiological results, on day + 56, levofloxacin 750 mg every 24 h plus doxycycline 100 mg every 12 h were prescribed.

Baseline (A) and control (B) PET performed in the first patient. A FDG baseline PET performed before the start of antibiotic therapy; arrows mark tracer hyperaccumulation at the soma of the L1 and L2 vertebrae (SUV max 16.2). B control PET performed after 8 weeks of antibiotic therapy; tracer hyperaccumulation no longer evident at L2 soma level

Polymerase chain reaction (PCR) (day + 59) for Mycoplasmataceae showed urinary and vaginal colonization by M. hominis and Ureaplasma urealyticum, not associated with genital symptoms of infection. Since Mycoplasma can cause infections of cell cultures, we reviewed the summary of critical quality attributes of the patient’s CAR-T product and found that it had tested negative by PCR for Mycoplasma spp.

A follow-up FDG-PET performed after 3 and 8 (Fig. 1B) weeks of antibiotic therapy documented first reduction and later almost complete resolution of spondylodiscitis, with FDG hyperaccumulation no longer evident at L2 soma, but the relapse of lymphoma was present. PCR search of Mycoplasmataceae was negative for M. hominis and U. urealyticum on both urine and vaginal swabs (day + 88).

The combination antibiotic therapy for Mycoplasma spondylodiscitis with levofloxacina and doxycycline was well tolerated but interrupted at 10 weeks (instead of the planned 12 weeks), as the patient expired due to lymphoma progression on day + 128 after CAR-T therapy.

A 50-year-old woman with congenital hypogammaglobulinemia (previously on replacement therapy) presented at the Emergency Department with a 3-month history of malaise, asthenia, back pain, and ankle pain. She was admitted to a different hospital (day 0, 27/12/2022), where she underwent several radiological assessments that revealed multiple abscesses localized in pelvic and perineal muscles (the largest 5 × 8 × 1.6 cm), pleural empyema, and right ankle arthritis. All the cultures performed (of blood, pleural liquid, glute abscess fluid, hip arthrocentesis fluid, and ankle arthrocentesis fluid) came up negative. At that time, all the immunoglobulin classes were below the lower limit of detection since the patients had not recieved immunoglobulin replacement therapy for several months.

As fever, pain, and inflammation persisted, empirical broad-spectrum antimicrobial therapy was started: first, with daptomycin plus metronidazole and meropenem, and then with ceftaroline, fosfomycin, ceftolozane/tazobactam and caspofungin.

Clinical conditions did not improve and generalized malaise with fever persisted. The patient was therefore transferred to our regional reference center for infectious diseases (day + 42), where antimicrobial therapy was discontinued. Cultures of purulent wounds (localized at the site where previous thoracic and gluteal drainages were placed) were performed: all three grew M. hominis after 3 days of incubation (day + 45); molecular analyses through PCR of thoracic wound sample confirmed the presence of M. hominis (day + 45).

PCR screening for Mycoplasmataceae (day + 52) showed urine colonization by U. urealyticum and rectal colonization by M. hominis, not associated with local symptoms of infection.

Based on microbiological findings, on day + 45, levofloxacin 750 mg every 24 h was started.

A baseline FDG-PET performed on day + 48 (Fig. 2) showed high tracer uptake within the organized pleural effusion (SUV max 8), pelvic abscesses (SUV max 11), and right tibia-calcaneal joint (SUV max 8). As the patient was persistently confused since her admission, a brain MRI was performed (day + 51), showing mild signal hyperintensity in T1 along the profile of supratentorial ventricular system, suspected of micro-abscess. The cerebrospinal fluid chemical-physical analysis (day + 58) was significant only for moderate damage of blood–brain, while culture and PCR for Mycoplasmataceae were negative.

Baseline (A) and control (B) PET performed in the second patient. A Baseline PET performed before the start of antibiotic therapy. High tracer uptake in pelvis (A1), at internal obturator muscles of both sides (A2) and on the left extending to the external obturator muscle and great adductor muscle (A3) (SUV max 11). Concomitant high FDG uptake at the right tibio-calcaneal joint extending to the lateral aspect of the calcaneus and plantar region (A4) (SUV max 8). B Control PET performed after 6 weeks of antibiotic therapy. Marked reduction in size and hypermetabolism compared with previous control and suspicious for proportion of active disease at pelvis (B1). Residual modest tracer hyperaccumulation at the internal obturator muscles (B2) and external obturator muscle and great adductor muscle (B3) (SUV max 5). These findings are reported as borderline regarding diagnostic significance. No more significant accumulation evident at the right tibio-calcaneal joint (B4)

The fever resolved after 72 h of levofloxacin therapy, and ankle pain and swelling improved rapidly. Levofloxacin was continued for a total of 6 weeks, after which (day + 84) persistent rectal colonization by M. hominis was documented, while U. urealyticum was no longer detected in urine.

A second FDG-PET performed at the end of antibiotic therapy (day + 90) (Fig. 2) revealed the marked reduction of tracer uptake in the internal, external, and great adductor muscles (sites of pelvic abscesses at baseline, SUV max 5), and complete resolution of uptake in the ankle. During subsequent hospital admissions a year later, there was no relapse of M. hominis infection.

Microbiological culture records from out institution from the years 2014–2023 did not reveal any additional cases of extragenital M. hominis infection.