Introduction

Mycoplasma belongs to the class Mollusca, which is characterized by the absence of a cell wall. Generally, Mycoplasma hominis colonizes the urogenital tract and can cause urogenital tract infections such as pelvic inflammatory disease or chorioamniotic infection.1 Although infections outside the urogenital tract are relatively rare, there are still reports of M. hominis causing bacteremia combined with pneumonia,2 mediastinitis after cardiac surgery,3 endocarditis,4 neonatal meningitis,5 etc. More importantly, treatment can be challenging because of M. hominis is the intrinsic antibiotic resistance to agents that work on bacterial cell wall synthesis, such as vancomycin, ceftriaxone, meropenem, metronidazole, etc.2 In addition, M. hominis infection has no typical clinical manifestations. Because of the lack of a cell wall, Mycoplasma cannot be observed by common staining methods, such as Gram staining, which increases the difficulty of clinical diagnosis and treatment of M. hominis infection.6 In this case, M. hominis was precisely identified as the pathogen using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) or 16SrRNA sequencing, and bacteremia and pleural infection were effectively controlled by timely treatment based on the results of antibiotic susceptibility testing (AST).

Case

A 56-year-old man with multiple left rib fractures (4–12 ribs), pelvic fractures with retroperitoneal hematoma, and the traumatic diaphragmatic hernia was treated with internal fixation of rib fractures, pleural adhesion release and diaphragmatic hernia repair in emergency surgery, then cefotiam was used as a prophylactic to prevent and control infection. On the fourth postoperative day, the patient had severe symptoms of infection, with the highest temperature of 39.2°C and a small amount of fluid (approximately 160 mL) in the right thoracic cavity. The procalcitonin levels were 1.76 ng/mL (reference range, 0–0.05ng/mL) and rapid C-reactive protein levels were 63.41 mg/L (reference range, 0–5.0mg/L), these indicators of infection were significantly increased. The antibacterial drug was immediately replaced with biapenem, and no improvement in the clinical symptoms was observed. Imipenem and linezolid were successively administered on postoperative day 9. However, on postoperative day 20, the patient still had a fever, pleural effusion, and suppurative wound exudation.

Blood cultures were collected on postoperative day 7 and 9. Blood Culture Instruments (Thermo Field, USA) all indicated positive after two days of blood culture, and no pathogen was detected in the positive cultures by Gram or Wright’s staining. Tiny, non-hemolytic, transparent colonies were observed on the third day of inoculation with the Columbia blood agar plate (Thermo Field, USA). (Figure 1A). Similarly, tiny, non-hemolytic, and transparent colonies grew on the Columbia blood agar plate of pleural fluid sample cultures three days later. (Figure 1B). Thus, the Columbia blood agar plate was cultured for five days, and transparent and tiny colonies were still observed (Figure 1C). However, typical pathogen structures were not detected by Gram or Wright’s staining. A subculture of blood and pleural fluid samples on the mycoplasma medium (A7 solid medium) presents as fried egg-type colonies after 5 days of incubation.(Figure 1D).

Figure 1 Representative results of sample culture (A) Tiny, non-hemolytic, and transparent colonies grew on the Columbia blood agar plate of blood-positive cultures three days after inoculation. (B) Tiny, non-hemolytic, and transparent colonies grew on the Columbia blood agar plate of pleural fluid sample cultures three days after inoculation. (C) On day 5, transparent and tiny colonies were observed on the blood agar plates with blood cultures. (D) Fried egg-type colonies were observed on mycoplasma medium after 5 days of incubation.

These tiny colonies were identified as M. hominis by MALDI-TOF MS EXS3000 (Zybio, China) with an identification score of 2.31 (Figure 2). Subsequently, M. hominis was also detected in the wound pus sample. AST using a commercial kit (broth dilution method, Zhongaisheng, Hebei, China) after incubating at 35–37°C under aerobic conditions for 48 hours, the color change of the detection hole can be judged by visual detection. Yellow is negative, clear and transparent red is positive. The AST results showed that M. hominis was susceptible to doxycycline, minocycline, josamycin, sparfloxacin, and spectinomycin but resistant to azithromycin, clarithromycin, norfloxacin, roxithromycin, and ofloxacin. In addition, it is sensitive to high concentrations of ciprofloxacin and levofloxacin. (Figure 3). Based on AST and further multidisciplinary discussions, moxifloxacin was selected as targeted therapy for M. hominis infection, and cefoperazone/sulbactam was combined to prevent the infection of other gram-negative bacteria. The patient’s infectious condition was alleviated after two weeks of medication. On postoperative day 36, the patient’s blood culture results were negative and there were no other signs of clinical or microbial infection, suggesting that the infection was completely controlled. The diagnostic and treatment processes of the patient are shown in Figure 4. Colonies were further identified as M. hominis by 16sRNA sequencing (primers: 27F, AGAGTTTGATCMTGGCTCAG; 1492R, GGTTACCTTGTTACGACTT) with an identification rate of 99% (NCBI Sequence ID:gb|CP011538.1|).

Figure 2 Peaks information of M. hominis using MALDI-TOF MS.

Figure 3 The results of antibiotic susceptibility testing of M. hominis..

Figure 4 The diagnosis and treatment process of the patient.

Discussion

The class Mollicutes was established in the 1960s to include mycoplasmas and other related organisms. Currently, it consists of four orders, five families, eight genera, and over 200 known species of humans, vertebrates, arthropods, and plants. Among these, at least 17 species have been documented, primarily in the respiratory or genitourinary tracts.7 Sixteen species of Mycoplasma have been isolated from humans, with six identified as pathogenic: Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, Mycoplasma fermentans, Ureaplasma parvum, and Ureaplasma urealyticum.8

Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals in 2022–2023, only 0.5% of surgical site infections were caused by other bacteria (non-gram-positive or negative bacteria), and only 0.1% of mycoplasma species have been reported in HIV-infected people in France.9 Here, we present a rare case of bloodstream and pleural infections caused by M. hominis following multiple pelvic and rib fractures. We reviewed the literature over the past decade and found three reports of bloodstream infections combined with pleural infections caused by M. hominis after trauma or surgery and nine reports of pleural infections caused by M. hominis after trauma or surgery (Table 1).

Table 1 The Summary of Bloodstream Infections and Pleural Infections Caused by M. hominis After Trauma or Surgery

Postoperative fever, often accompanied by pleural effusion or wound suppurative inflammation, was the most common clinical feature observed in these cases. All the patients recovered after receiving targeted antimicrobial therapy. Notably, 91.67% (11/12) of the patients underwent relevant surgical interventions. Invasive surgical procedures, such as endotracheal intubation and urinary catheterization, have been identified as potential factors contributing to the opportunistic invasion of M. hominis and subsequent bloodstream infections or infections at other sites.

Due to the lack of a cell wall and the high polymorphism of M. hominis, Gram staining is ineffective in identifying this pathogen, leading to challenges in clinical detection and potentially missed diagnoses. In addition, the transition from clinical empiric antimicrobial therapy to targeted antimicrobial therapy has also been challenged and jeopardised. Slow-growing M. hominis often requires several days for colony formation on traditional culture media, delaying diagnosis.6,17 Extending the culture time can effectively enhance detection rates, and some studies suggest culturing under anaerobic conditions.1,3,16 Aerobic and anaerobic cultures can be inoculated simultaneously to enhance the detection rate of M. hominis. Despite this approach, some cases of M. hominis infection may still be overlooked. Therefore, molecular detection methods such as 16sRNA sequencing and metagenomic next-generation sequencing (mNGS) are considered timely and effective diagnostic techniques for detecting M. hominis infection. The absence of effective or rapid microbial identification and targeted therapy with antimicrobials can lead to persistent infections, prolonged hospital stays and unnecessary waste of medical resources. The successful management of this case hinged on culturing M. hominis from both the blood and pleural effusion, followed by 16sRNA sequencing analysis to confirm the pathogen. Based on drug sensitivity experiments and expert advice, targeted moxifloxacin treatment was chosen, resulting in a successful outcome. Laboratory identification and clinical diagnosis of M. hominis infection can be challenging, with the routine clinical empirical use of broad-spectrum antibiotics often proving ineffective. Therefore, early, rapid, and accurate detection of pathogens is essential. The possibility of M. hominis infection should be considered in patients showing symptoms of infection postsurgery, such as persistent fever and elevated levels of C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6), where conventional broad-spectrum antibiotic treatment fails, consideration should be given to the possibility of M. hominis infection. More importantly, antibiotic susceptibility testing for M. hominis is crucial but poses challenges for most laboratories. Quinolone antibiotics such as levofloxacin and moxifloxacin are typically effective against M. hominis, although instances of drug resistance due to genetic mutations have been reported.18,19 Our study involved antibiotic susceptibility testing of cultured M. hominis, which revealed that doxycycline, minocycline, josamycin, and spectinomycin exhibited higher sensitivity.

According to literature descriptions, M. hominis has been detectable in urine samples in 20–40% of healthy individuals.20 The patient in this report had multiple pelvic fractures. Whitson et al suggested that urogenital trauma may contribute to urinary tract injury. Genital commensal bacteria create pathways for invasion of the pelvis and abdomen.21 Therefore, it is hypothesized that the infection originated from an ascending thoracic infection due to pelvic fractures, leading to bloodstream infection after surgery involving multiple pelvic and thoracic fractures, although this hypothesis was not confirmed. M. hominis was isolated from the pleural effusion and blood, but no homology analysis was conducted between the pelvic effusion, pleural effusion, or blood samples. Nonetheless, this speculation provides valuable clinical insights. Patients undergoing invasive procedures through the genitourinary tract following trauma or surgery, especially those with postpelvic urinary system trauma, are at a high risk of M. hominis infection. Bloodstream infections can occur simultaneously with infections at other sites. Therefore, postoperative wound fluid irrigation and drainage are crucial interventions along with appropriate antibiotic therapy.12 Based on this case report, we recommend preoperative screening for M. hominis in the urinary and respiratory systems of these patients to proactively identify potential risks.

Conclusion

This case demonstrates that M. hominis can lead to infections beyond the genitourinary system, particularly in patients who have undergone invasive procedures or experienced trauma in the genitourinary tract. In cases where patients exhibit postoperative fever and do not respond to standard broad-spectrum antibiotic therapy, clinicians should consider the potential presence of mycoplasma infection.

Data Sharing Statement

The original contributions of this study are included in the article. Further inquiries can be directed to the corresponding authors.

Ethics Approval and Consent

Ethical approval was obtained from the Shanghai East Hospital (Tongji University School of Medicine). The patient provided written informed consent to participate in this study.

Acknowledgments

We are grateful to the patients for their cooperation in the diagnostic process.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, sample culture and isolation, antibiotic susceptibility testing, analysis, and interpretation, or in all these areas, took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; agreed on the journal to which the article has been submitted; and agreed to take responsibility and be accountable for the content of the article.

Funding

The authors declare that they received no funding for this study.

Disclosure

The authors have no competing interests to declare relevant to the content of this article.

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