A case of hematogenous dissemination due to Mycoplasma hominis with fa

Introduction

Mycoplasma hominis is one of the common colonizing organisms of the genitourinary tract and usually causes associated infections in the genitourinary tract.¹ Recently, infections caused by M. hominis outside the urogenital tract have been on the rise, including postoperative infections,^2–5arthritis,⁶ pneumonia,⁷ meningitis.⁸ However, M. hominis infections transmitted via the bloodstream are relatively rare, and their source is often difficult to identify.⁹ Such infections predominantly occur in immunocompromised individuals with indwelling urinary catheters.^6,10 Due to the fastidious nutritional requirements and slow growth of M. hominis, routine blood cultures seldom recover the organism, rendering bloodstream infections easily overlooked. As an atypical pathogen, M. hominis remains under-recognised clinically, especially at non-genitourinary sites. Moreover, the absence of a cell wall confers intrinsic resistance to many first-line antimicrobials, so bloodstream infections caused by this organism continue to pose substantial diagnostic and therapeutic challenges.

MALDI-TOF MS is a rapid identification technique based on microbial proteomic fingerprinting and has become a transformative tool in clinical microbiology, enabling fast and accurate characterization of atypical pathogens such as M. hominis. We report a case of disseminated infection caused by M. hominis in a patient following lumbar spine surgery, with a false-negative blood culture result. The patient experienced severe infection leading to wound tissue necrosis and substantial effusion, with the surgical site remaining unhealed for an extended period. In addition, the patient developed pulmonary infection and effusion in multiple serous cavities. The investigation revealed that microtrauma to the urethral mucosa caused by catheterization allowed the colonization of M. hominis to invade the bloodstream, which was identified as the primary cause of disseminated infection.

Case Presentation

A 72-year-old male patient presented to our hospital on July 27, 2024, with complaints of recurrent lower back pain and radiating pain in the left lower limb for over 1 year. He was diagnosed with lumbar disc herniation with radiculopathy and lumbar spondylolisthesis and was subsequently admitted for surgical treatment.

On admission, the patient reported good overall health, with no history of hypertension, diabetes, or other underlying diseases. The patient was not taking any immunosuppressive agents or other medications, and his medical history was unremarkable. A physical examination after admission revealed no significant abnormalities. Preoperative imaging revealed that the patient had mild fatty liver disease and mild regurgitation into the mitral and tricuspid valves. Laboratory tests, including liver function, renal function, routine blood tests, and routine urine tests, showed no significant abnormalities. A urinary catheter was placed preoperatively and cefazolin sodium (1.0 g iv bid) was administered prophylactically to prevent infection. The patient underwent lumbar fusion surgery, combined with laminoplasty and decompression, on July 29, 2024.

On postoperative day 2, the patient developed a fever with a peak temperature of 39.2°C. Laboratory tests revealed a white blood cell (WBC) count of 13.4×10⁹/L, with 78% neutrophils, 12.8% lymphocytes, and a C-reactive protein (CRP) level of 65.9 mg/L (reference range 0–6 mg/L). Examination of the surgical site showed that the wound was clean and dry with no significant bleeding or exudate. Based on empirical judgment, the antibiotic was changed to ceftriaxone (2.0 g iv bid) to prevent wound infection. However, the patient continued to experience recurrent chills and fever 2 weeks after surgery, with the highest temperature reaching 38.7°C and persistent elevation of blood inflammatory markers. Specifically, the WBC count peaked at 9.4×10⁹/L, CRP reached a maximum of 155.3 mg/L, and serum amyloid A (SAA) peaked at 320 mg/L (reference range 0–10 mg/L). Urinalysis revealed abnormalities including occult blood 2+. Urine flow cytometry revealed red blood cell (RBC) counts of 45.8/μL (reference range 0–18/μL) and WBC counts of 22.3/μL (reference range 0–13/μL). On postoperative day 5, the urine and the first set of blood samples (BacT/ALERT bioMérieux, France) were cultured. The antibiotic regimen was adjusted to piperacillin/tazobactam (4.5g iv q8h) combined with vancomycin (1g iv q12h). Despite negative urine and blood cultures (both aerobic and anaerobic) after two and five days, respectively, the patient’s condition remained unchanged. On postoperative day 10, the patient’s temperature and inflammatory marker levels remained elevated, and he developed intermittent cough, unbearable pain, and swelling at the surgical site. Chest CT (Figure 1A and B) revealed scattered patchy high-density shadows in both lungs, left interlobar effusion, bilateral pleural effusion, a small amount of pericardial effusion, and multiple enlarged mediastinal lymph nodes. Lumbar MRI (Figure 1C) revealed soft tissue swelling and subcutaneous effusion in the lumbar and dorsal regions. Examination of the surgical site revealed mild redness and swelling of the surrounding skin with a fluctuating sensation in the subcutaneous tissue. On that afternoon, the surgical wound began to exude fluid and dehisced the following day. We performed debridement and collected exudate samples for culture on two consecutive days while also obtaining the second set of blood cultures. Considering the wound and pulmonary infections, as well as the potential for pleural or pericardial infection based on the comprehensive examination results, we adjusted the antibiotic regimen to imipenem/cilastatin (1.0 g iv q8h) in combination with vancomycin (1 g iv q12h) after a multidisciplinary consultation.

On the morning of postoperative day 13, debridement surgery was performed following multidisciplinary discussion of the complex case. Preoperatively, laboratory tests revealed pinpoint colonies on Columbia blood agar (AnTu Bio, China) from two exudate samples (Figure 2A), with no bacterial cells detected by gram staining (Figure 2B). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker, Germany) identified the pathogen as Mycoplasma hominis, with a mass spectrometry score of 2.4 (scores above 2.0 are considered reliable for species-level identification), and the mass spectrometry protein fingerprint is shown in (Figure 2C). During debridement, poor healing of the subcutaneous tissue and deep fascia was observed, with a cavity formed over the spinous process, containing a large amount of dark red effusion, odorless and partial necrosis, and inflammatory changes in the soft tissues within the wound. The inflammatory tissues and exudates within the wound were thoroughly removed, and the wound was irrigated with copious amounts of normal saline, hydrogen peroxide, and povidone-iodine solution, followed by re-suturing of the deep fascia and wound. Deep effusion samples from wounds were collected and inoculated into routine bacterial and mycoplasma cultures (Zhuhai Yinke Bio, China). Considering all factors, the antibiotic regimen was adjusted postoperatively to moxifloxacin (400 mg iv qd) in combination with doxycycline (100 mg PO q12h) to target Mycoplasma infection and prevent other bacterial infections.

Figure 2 Laboratory Characteristics of M. hominis. (A) After 3 days of culture on Columbia blood agar with incision exudate, pin-like, non-hemolytic, transparent colonies appeared (4-fold macro photography). (B) Gram staining of the colony smear showing no bacterial body structure under the microscope. (C) Protein fingerprints detected by MALDI-TOF.

On postoperative day 15, deep exudate samples obtained during debridement surgery were positive for M. hominis and no other bacterial growth was detected. Drug sensitivity testing (Zhuhai Yinke Bio, Figure 3A) revealed that M. hominis was susceptible to doxycycline, minocycline, josamycin, and spectinomycin; showed intermediate sensitivity to gatifloxacin; and was resistant to ciprofloxacin, sparfloxacin, levofloxacin, roxithromycin, azithromycin, and clarithromycin. To explore the source of M. hominis infection and the possibility of pulmonary M. hominis infection, we cultured urethral swabs, coronal sulcus mucosa, and sputum samples, all of which yielded positive results for M. hominis, and no other suspicious pathogens were detected. Interestingly, although the second set of blood cultures remained negative after 5 days according to the instrument (BacT/ALERT bioMérieux), both bottles of the culture, when inoculated onto blood agar plates and Mycoplasma culture media, yielded positive results for M. hominis (Figure 3B). Moreover, the drug sensitivity results for M. hominis cultured at different sites are consistent. We also performed a simple cluster analysis of the strains isolated from the four different sites using MALDI BIOTYPER OC3.1 software, and the results showed that these strains belonged to the same cluster (Figure 3C). After 15 days of combined drug therapy, the patient’s infection symptoms disappeared, inflammatory marker levels gradually decreased, and the wound healed. Although body temperature fluctuated during this period, two consecutive cultures were negative. The patient was discharged on postoperative day 31 after suture removal and continued to take doxycycline for another 20 days. On postoperative day 55, he came to the hospital for a follow-up visit and the recovery is good. The timeline of the diagnosis and treatment process is shown in (Figure 4).

Figure 3 Blood Culture and Antimicrobial Susceptibility Results of M. hominis and MALDI BIOTYPER clustering analysis dendrogram. (A) Results of antibiotic susceptibility testing for M. hominis. Red wells indicate the growth of M. hominis, corresponding to drug resistance; yellow wells indicate no growth of M. hominis, corresponding to drug sensitivity. (B) After 5 days of negative results reported by the blood culture instrument, the culture grew a small number of pinpoint-like, non-hemolytic, transparent tiny colonies on Columbia blood agar after 3 days of culture (4-fold macro photography). (C) MALDI BIOTYPER clustering analysis dendrogram.

Figure 4 Timeline showing the entire diagnosis and treatment process for this case.

Discussion

The diagnosis of M. hominis infection outside the urogenital tract is challenging. First, M. hominis infection often presents with fever and elevated inflammatory markers, such as WBC, CRP, and neutrophil percentage (NEUT%).¹⁰ These clinical manifestations are nonspecific, and infections outside the urogenital tract are relatively rare and easily overlooked. Second, traditional detection methods are limited by the fastidious growth requirements of mycoplasmas, which require specialized culture media and are difficult to grow in routine cultures. M. hominis is the only mycoplasma that can be detected in routine cultures, such as on blood agar plates and in blood cultures.¹⁰ The growth of M. hominis on blood agar is slow, often requiring about 3 days to form visible colonies, which are extremely small and easily overlooked. Moreover, sodium polyanethole sulfonate (SPS), an anticoagulant commonly added to commercial blood culture bottles, may inhibit the growth of M. hominis, leading to poor culture outcomes.¹¹ In addition, the relatively low amount of CO₂ produced during the growth of M. hominis, which is below the detection threshold of the instruments, may also result in false-negative results.¹² In this case, two sets of blood cultures were tested using the BacT/ALERT microbial culture monitoring system, and both yielded negative results. Had it not been used for the isolation of M. hominis from wound exudate, which prompted further culturing, this infection would have been difficult to detect. This highlights the significant challenge of diagnosing M. hominis bloodstream infections. Furthermore, the lack of a cell wall in mycoplasmas means that Gram staining cannot detect identifiable bacterial cells, which is also one of the reasons for the diagnostic difficulties. To address this issue, MALDI-TOF MS can be used to confirm the cultured colonies with rapid and reliable results. Nevertheless, MALDI-TOF MS requires visible colonies before analysis and is therefore less expeditious than molecular approaches such as PCR or next-generation sequencing (NGS). On postoperative day 5 the physician intended to order NGS to determine the cause of fever. However, the test was not available in our laboratory, so the plan was abandoned.

Given that Mycoplasma species lack a cell wall, they exhibit intrinsic resistance to β-lactam antibiotics and vancomycin, both of which target the cell wall. Antibiotics are frequently used for the prevention and empirical treatment of surgical site infections. Thus, in this case, the patient’s condition did not improve despite multiple antibiotic changes. Commonly used antibiotics against M. hominis include tetracyclines, quinolones, and macrolides. However, M. hominis often exhibits resistance or low susceptibility to 14- and 15-membered macrolides (such as erythromycin, roxithromycin, clarithromycin, and azithromycin). This is because the target site of these antibiotics is the 23S rRNA V domain of the M. hominis ribosome, which has specific structural alterations (eg, methylation at the A2058 site or nucleotide mutations) that prevent the drugs from effectively binding to the 50S ribosomal subunit, thereby inhibiting their ability to suppress protein synthesis.¹³ With the emergence of resistance gene mutations, increasing cases of M. hominis resistance to quinolones and tetracyclines have been reported.^14–16 Therefore, antimicrobial susceptibility testing should be performed whenever possible to guide precise treatment. In the absence of susceptibility results, a combination of fluoroquinolones and doxycycline may be the preferred regimen for treating M. hominis infections.⁹ It is important to note that M. hominis is intrinsically resistant to aminoglycosides. However, many commercially available mycoplasma susceptibility testing kits contain gentamicin. The apparent susceptibility results can lead to misleading clinical treatment and should be avoided.

Although the sources of infection have been identified in a few cases of M. hominis infection, such as prostatic abscesses¹⁷ and transplant donors,^18,19 the source of M. hominis infection outside the urogenital tract is generally difficult to determine. Most patients with extragenital infections have a history of surgery and typically undergo preoperative urinary catheter placement. Therefore, it is generally speculated that M. hominis may enter the bloodstream via the urethra during catheterization or be introduced through contaminated surgical instruments.²⁰ In this case, M. hominis colonization was confirmed in the patient’s urinary tract, and the antimicrobial susceptibility results of M. hominis isolated from other sites were consistent. MALDI-TOF MS cluster analysis showed that these strains belonged to the same clade, thereby confirming that the source of infection was M. hominis, which colonizes the urinary tract. The patient’s urinalysis and pulmonary imaging results were normal at admission; however, postoperative urinalysis revealed hematuria and elevated red blood cell (RBC) counts, suggesting that urethral catheterization may have caused mucosal damage in the urinary tract. Colonized M. hominis likely invaded the bloodstream through the damaged mucosa, causing an infection and subsequent persistent fever. Postoperative immunosuppression facilitates dissemination of the pathogen via the bloodstream, leading to infections at the surgical site and in the lungs. The patient’s pleural and pericardial effusions may have been caused by pulmonary infection, but in light of the literature,²¹ the possibility of M. hominis causing pleuritis and pericarditis could not be ruled out. The limitation of the present study is that more reliable molecular biology-based homology analyses were not carried out.

Conclusion

In this case, urethral mucosal damage caused by catheterization enabled colonized M. hominis to invade the bloodstream, leading to postoperative bacteremia. The patient’s transient immunosuppression after surgery facilitated the spread of infection. Therefore, patients who have undergone catheterization are at high risk of M. hominis infection. When such patients present with persistent fever and negative routine cultures, M. hominis infection should be suspected. Notably, blood cultures may produce false-negative results, leading to underestimation of its true incidence. Therefore, targeted mycoplasma culture followed by MALDI-TOF MS identification should be performed promptly.

Ethics Approval and Informed Consent

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. The study was reviewed and approved by the Ethics Committee of the Affiliated Hospital of Shaoxing University, with the ethical approval number (2024(Research)-015-01), and was conducted in accordance with the principles of the Declaration of Helsinki.

Acknowledgments

We acknowledge the contributions of other clinical and laboratory staff at the Affiliated Hospital of the Shaoxing University. We are grateful for the understanding and consent of the patient and his family.

Author Contributions

All authors made significant contributions to the work reported, whether in the conception, study design, execution, data acquisition, analysis, and interpretation, or in all these areas; have drafted, revised, or critically reviewed the article; have given final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This study was supported by the Shaoxing Municipal Health and Family Planning Science and Technology Project (Grant No. 2024SKY084) and the Medical Science and Health Science Program of Zhejiang Province (Grant No. 2024KY485).

Disclosure

The authors report no conflicts of interest in this work.

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