Gemella morbillorum isolated from a pelvic abscess in an HIV-positive patient with squamous cell carcinoma of the perianal region

Abstract

Gemella morbillorumis a known commensal organism of the human oropharynx, gastrointestinal tract and genitourinary tract which is a rare cause of infections and even more rarely implicated in skin and soft tissue infections. We present a case of a young, HIV-positive patient with squamous cell carcinoma of the perianal region who presented with difficulty initiating urination for 1 week as well as increasing left leg swelling. His CD4 count was found to be 186, predisposing him to infection, and he had also received chemotherapy in the past year for his malignancy. He was febrile and tachycardic on presentation and admitted for further care. CT scan of the pelvis at time of admission demonstrated a pelvic abscess. Aspiration cultures ultimately grew G. morbillorum. Despite initial improvement with drainage and targeted antimicrobial therapy, the patient’s abscess recurred, and he ultimately elected transition to hospice due to worsening prognosis of malignancy.

Background

Gemella morbillorum is a gram-positive facultative anaerobe, which is a known commensal organism of the human oropharyngeal and upper gastrointestinal (GI) tract.¹ Originally classified as part of the Streptococcus genus, it was reclassified into the Gemella genus after further studied demonstrated significant similarity to G. hemolysans.² In the literature, G. morbillorum has a well-documented role in infective endocarditis, particularly valvular disease.^3–5 It has also been implicated in visceral abscess formation in multiple systems, including the liver and lungs.^{6 7} However, there are only two reported cases in the current literature of soft tissue infection with G. morbillorum grown from abscess fluid culture.⁸ The case presented here provides evidence of G. morbillorum as a primary cause of pelvic abscess in an HIV-positive patient and serves to raise awareness of the role of this organism in skin and soft tissue infections, especially in severely immunocompromised patients.

Case presentation

This is the case of a 30-year-old man with a history of HIV and unresectable squamous cell carcinoma of the perianal region and scrotal sac who presented to the emergency department complaining of difficulty initiating urination for 1 ½ weeks. He also noted left leg swelling and pain that had gradually been increasing over the past 2–3 weeks. He did not endorse tactile fever, did not measure his temperature at home and denied any chills; review of systems was completed, and he denied cough, shortness of breath, neck stiffness, nausea, vomiting, diarrhoea, blood in his urine, abdominal pain or any other acute symptoms at that time.

The patient had a history of HIV as noted above. A CD4 count was ordered at the time of admission and measured an absolute count of 186 cells/μL. His currently prescribed antiretroviral therapy regimen consisted of single-pill combination therapy with elvitegravir–cobicistat–emtricitabine–tenofovir alafenamide; on further questioning, he noted that he did not take this medication every day as prescribed. He was unsure how often he took the medication but indicated that it was at least a few times per week. He was not on any antibiotic, antiviral or antifungal prophylaxis at time of admission.

Regarding his malignancy, the patient had undergone Mohs surgery to the perirectal region in 2017, followed by concurrent chemoradiation with cisplatin. He had recurrence with spread to local lymph nodes and subsequently underwent carboplatin and 5-fluorouracil salvage chemotherapy within the past year. He had started pembrolizumab treatment 2 weeks prior to this presentation. The patient was currently unemployed. He reported tobacco use of five cigarettes per day since his teens. He denied intravenous drug use; he denied daily alcohol use or binge drinking but did report drinking one to two beers a few days per week.

On presentation, he was found to be consistently tachycardic, as high as 140 beats/min and febrile to 38.8°C. An open wound was noted on the left medial thigh from which yellow pus could be expressed. The left lower extremity showed oedema to the mid-thigh; there was also decreased range of motion in all directions at the left hip secondary to pain, with the most pain elicited on abduction and flexion.

Investigations

Laboratory evaluation demonstrated leucocytosis (11.5×10⁹/L) with 82% neutrophils, anaemia (haemoglobin 74 g/L), hyponatraemia (131 μmol/L) and hypochloraemia (92 μmol/L). Urinalysis demonstrated a turbid specimen with 1+leucocyte esterase, 5–10 white cell count (WCC) and trace bacteria. Two sets of blood cultures were obtained at time of admission and grew Pseudomonas aeruginosa within 1 day. No growth was noted in the anaerobic specimen bottle through 5 days follow-up. No G. morbillorum was identified on any blood specimen gram stain or culture.

The patient underwent urinalysis which was collected in the emergency department, showing a turbid specimen with 1+leucocyte esterase, 5–10 WCCs and trace bacteria. Unfortunately, urine culture was ordered but not completed during admission. Given the fact that P. aeruginosa was not isolated from his abscess and G. morbillorum was not found in his blood, there was little suspicion that his abscess had led to bacteraemia. He also had no symptoms in other systems, such as respiratory, to indicate another focus of infection. With subjective urinary symptoms, a borderline infectious urinalysis as described above, and no other focus of infection, the patient was clinically diagnosed with bacteraemia secondary to urinary tract infection (UTI) in the setting of urinary retention.

Given the patient’s bacteraemia, he was evaluated with transthoracic echocardiogram, which did not show any vegetations or other abnormalities. Given the lack of other clinical sequelae of the disease, there was low suspicion for endocarditis, and no further workup was pursued.

On CT abdomen/pelvis, he was found to have left inguinal gas and fluid collection (figure 1) connecting to the open thigh wound suggestive of a pelvic abscess, as well as mild left hydronephrosis. It was noted that the gas and fluid collection abutted the urinary bladder and sigmoid colon; however, there was no radiological evidence of fistulous or other communication between the abscess, bladder and/or bowels.

Figure 1.

Transverse CT pelvis demonstrating a soft tissue fluid and gas collection in the left pelvic region prior to treatment.

The patient had undergone CT imaging of his pelvis 2 months prior to this admission which showed multiple necrotic lymph nodes in the pelvis, at that time without fluid or other indication of abscess formation; he was also free of fever or other systemic signs of infection at that time. During this admission, CT imaging of the pelvis demonstrated a new fluid collection in the same area where there had been necrotic lymphadenopathy noted 2 months prior. Putting these together, radiology indicated that the abscess had formed at the site of necrotic lymphadenopathy, resulting in the diagnosis of left inguinal lymph node abscess.

Interventional radiology performed image-guided drainage of the pelvic abscess. Gram stain of the abscess fluid showed numerous gram-positive cocci, moderate gram-positive bacilli and few gram-negative bacilli. Subsequent culture isolates grew only G. morbillorum, confirmed by matrix-assisted laser desorption/Ionisation time-of-flight mass spectrometry (MALDI-TOF); no other organisms were identified by MALDI-TOF analysis of culture isolates. Of note, anaerobic cultures of the abscess fluid were not performed; considering this with the polymicrobial gram stain, it is most likely that this was, in fact, a polymicrobial abscess of which G. morbillorum was a predominant contributor.

Differential diagnosis

The main diagnostic breakpoint to consider was if the local pelvic infection was related to the P. aeruginosa bacteraemia or if they were separate, concurrent processes. The patient had blood cultures which grew P. aeruginosa, explaining his systemic symptoms of fever and tachycardia; there were no gram-positive cocci on blood culture gram stains, and no blood specimens grew G. morbillorum.

He also underwent interventional radiology (IR)-guided drainage of his left inguinal abscess; initial gram stain indicated numerous gram-positive cocci, a few gram-positive bacilli and a few gram-negative bacilli. Ultimately, MALDI-TOF testing of the cultured isolate demonstrated only G. morbillorum in moderate quantity, no other organisms, which led to the diagnosis of a local infection with G. morbillorum with a separate systemic infection with P. aeruginosa. As noted above, it remains possible that this was a polymicrobial infection with G. morbillorum as a predominant organism.

Treatment

The patient was diagnosed with chronic left inguinal lymph node abscess due predominantly to G. morbillorum infection. Concurrently, he was also diagnosed with P. aeruginosa bacteraemia, thought to be secondary to his UTI as described above.

After obtaining two sets of blood cultures, intravenous vancomycin, cefepime and metronidazole were started; of note, the initial abscess drainage described above occurred roughly 10 hours after the initiation of these empiric antibiotics. With receipt of abscess and blood cultures, vancomycin was discontinued with the patient having received 5 days of intravenous vancomycin therapy. Four days after the presentation, intravenous metronidazole was changed to oral metronidazole. After 18 days of intravenous cefepime therapy, the patient was transitioned to oral ciprofloxacin.

Given the concurrent P. aeruginosa bacteraemia, the oral ciprofloxacin and oral metronidazole regimen was recommended for a total of a 6-week course, which would have been roughly another 3 weeks of outpatient oral therapy after the 3 weeks of intravenous therapy received as an inpatient. He received 4 days of oral ciprofloxacin and metronidazole therapy as an inpatient before electing for hospice care.

No antibiogram was available for G. morbillorum given the lack of local susceptibility data available. The P. aeruginosa specimen isolated from blood was shown to be susceptible to ciprofloxacin. Current available standards indicate that Gemella species are generally pansusceptible, with penicillin, ceftriaxone and vancomycin being mentioned specifically as therapeutic options.⁹ Ciprofloxacin was thus deemed acceptable oral therapy, covering both blood and abscess infections.

As an inpatient, the patient also underwent image-guided left inguinal abscess drainage with IR shortly after starting antibiotic treatment as discussed above.

The patient’s urinary symptoms were attributed to significant pelvic lymphadenopathy, including the abscess, which were related to his cancer per radiology. Given his advanced malignancy and concern that this lymphadenopathy would remain stable at best, and more likely continue to progress, there was little hope that his retention and hydronephrosis would improve. Urology was consulted and placed a left nephrostomy tube to alleviate his hydronephrosis while he explored goals of care.

Two sets of blood cultures, which were drawn 24 hours after starting antibiotic therapy, demonstrated no growth through 5 days. His left nephrostomy tube had consistent output and his own urine production improved as well.

Outcome and follow-up

The patient completed the above described course of antibiotic therapy as an inpatient with negative follow-up blood cultures after starting treatment as described above, indicating clearance of the P. aeruginosa bacteraemia.

After CT-guided drainage and drain placement, the left pelvic abscess decreased significantly in size based on imaging; unfortunately, the patient underwent repeat imaging of his left pelvis with X-ray 5 weeks after his initial presentation which showed persistence of gas and fluid in the same area, indicating that he had not fully resolved the local infection. As he was on antimicrobial therapy with a drain in place, the lack of resolution was attributed to his poor immune status in the setting of HIV, active malignancy and ongoing immunotherapy.

While further antimicrobial therapy was initially indicated for a total of 6 weeks, given his overall poor prognosis from his malignancy, the patient elected for discharge to home hospice and antibiotics were discontinued on discharge.

Discussion

The patient at hand has multiple causes for immune deficiency, including poorly controlled HIV, multiple prior chemotherapy treatments and active immunotherapy. Furthermore, he had a recent history of multiple antimicrobial agents, predisposing him to antimicrobial resistance and development of his wound due to this relatively rare organism, G. morbillorum.

G. morbillorum is known to be a commensal organism of the human oropharyngeal, upper GI and genitourinary tract.¹ It is rarely the cause of infection in humans, and when it is isolated, has mostly been so in the setting of infective endocarditis.^3–5 To date, only two cases at a single centre have described skin and soft tissue infection with G. morbillorum,⁸ making its presence here as the cause of a soft tissue infection concerning for an expanding role as a virulent pathogen in humans.

Of note, there have been reported associations of G. morbillorum bacteraemia with certain malignancies. The strongest evidence is noted with colorectal carcinoma.^{10 11} Interestingly, Pushalkar et al presented a study in oral squamous cell carcinoma patients in which they sampled oral mucosa immediately adjacent to the tumour and then compared the composition of the bacterial flora to samples obtained in the oral cavity relatively distant from the tumour; they described a shift in bacterial colonisation in the near-tumour samples showing an increased proportion of certain gram-positive organisms, including G. morbillorum. ¹² Another study by Gong et al profiled the laryngeal flora in healthy patients and patients with laryngeal squamous cell carcinoma for comparison; Gemella species were isolated in a significantly higher proportion in the patients with laryngeal squamous cell cancer.¹³

We present a patient with perianal squamous cell carcinoma and local pelvic abscess, further suggesting a role of local bacterial flora disruption as either a cause or effect of squamous cell carcinoma. While the patient presented in our case had many other risk factors for developing his infection, the local presence of squamous cell carcinoma should be considered as a possible relationship to his G. morbillorum infection.

This case adds to the literature on the overall infective capability of G. morbillorum in immunocompromised patients, its possible local association with squamous cell carcinoma and its role as the predominant organism in skin and soft tissue infections. Further studies are needed to ascertain the role of G. morbillorum in soft tissue infections as well as its role in the pathogenesis of squamous cell carcinoma.

Learning points.

• Gemella morbillorum is a commensal organism of the human microbiome that can be virulent in the setting of severe immunocompromise.

• Skin and soft tissue infections in the setting of active malignancy can often present with uncommon pathogenic organisms due to altered local microflora.

• Specific pathogen-directed antimicrobial treatment with concurrent debridement of large soft tissue infections remains the most effective method for clearing infection, regardless of the rarity or other factors of the offending pathogen.