Discussion and conclusions
M. hominis is part of the normal inhabitant of the genitourinary tract [
6]. However, in line with publicly-available documents, it might disseminate to other body sites secondary to a disruption of the mucosa or in patients with autoimmune disorders, hypogammaglobulinemia, and other underlying immunosuppressions [
3,
12‐
15]. Herein, we described the clinical circumstances, treatment, and outcomes of a postoperative septic complication due to the microorganism after hip replacement. To the best of our knowledge, this is the first report of
M. hominis as the causative, fastidious agent of prosthetic hip infection in China.
To better understand the characteristics of postoperative infection after hip or knee replacement, PubMed was searched for literature review and 5 cases by
M. hominis in 4 reports were included for comparison (Table
1) [
16‐
19]. The literature review demonstrated that, including our case, the gender ratio of male/female suffered
M. hominis infection after joint or tip replacement was 5:1. The median age was 64 years old. Furthermore, as documented, CRP concentrations were available in 4 out of 5 cases, and all their CRP levels were higher than 100 mg/L. Our case also had an increased CRP (200 mg/L), hinting elevated CRP level would help in suspecting postoperative
M. hominis infection. The review also described that the most common and effective test for diagnosing joint or hip
M. hominis infection was the culture of wound exudation, joint fluid, and aspiration fluid of the knee [
16‐
19]. In our case,
M. hominis was recovered from subcutaneous puncture fluid and successfully identified. This showed that, if the tiny colonies grew on the blood agar plate without obvious bacteria shapes under gram-staining smears,
M. hominis should be suspected of being underlying pathogen [
16,
17]. Presently, the molecular methods, such as 16S rRNA sequencing or real-time PCR, might be used for the identification of infections caused by the bacterium [
17,
19].
Table 1
Summary of the reported cases of Mycoplasma hominis after joint or hip replacement
Case Number | 1 | 1 | 1 | 1 | 1 | 1 |
Age (years) | 62 | 71 | 76 | 66 | 54 | 59 |
Surgery | Left total knee replacement due to knee osteoarthritis. | Left total knee replacement. | Left knee joint replacement. | Bilateral total knee replacements 5 years ago and a left total hip replacement 2 years ago. | Implantation of a total hip prosthesis one month before. | Left hip replacement. |
Gender | Male | Male | Male | Female | Male | Male |
Fever | Yes | 39.7 °C | 38.7 °C | Yes | Yes | 38.5 °C |
Infection indicators |
CRP(mg/L) | 208.3 | 122.4 | 143.6 | NA | 374 | 200 |
WBC(× 109/L) | NA | 10.25 (Neutrophils 81.4%) | 11.83 (Neutrophils 88.3%) | 6.0 | 6.9 | 15.4 |
ESR(mm/hr) | NA | 61 | 63 | 101 | NA | 112 |
Microbiological test results | Bacterial and fungi culture of wound exudation and seepage demonstrated a negative growth, whereas the secretion collected in the operation suggested a positive M. hominis growth, identified by mass spectrometer. | Pinpoint, translucent colonies on Brucella agar after 2-day incubation of joint fluid, confirmed as M. hominis by 16S rRNA sequencing. | Anaerobic culture for 3 days incubation of joint fluid indicated the growth of M. hominis. | Cultures of the aspiration fluid of the knee revealed very small clear colonies were seen on the blood agar plates, present on both the aerobic and anaerobic plates. | At the time of admission, Gram stain of a swab taken from the wound of the right hip showed rare leukocytes but no bacteria, and cultures were negative. Cultures of the effusion collected via arthroscopy of the left knee remained negative. The biopsy of the inflamed tissue revealed no bacteria on Gram staining, and no growth after 14-day culture. M. hominis. Was identified via16S rRNA sequencing. | After 48 h of incubation on blood agar at 37 °C in a 5% CO2 atmosphere, tiny, non-hemolytic, transparent colonies were found on Columbia blood agar plates. |
Presentation of post-surgical infection | Blood seeping and pale clear liquid exudation from the wound were observed on the 3rd and 4th day after the surgery. | Three days after operation, there were redness and swelling, pain at surgical site. | One day after operation, fever, redness and swelling around knee were observed. | NA | Implantation of a total hip prosthesis one month before. Symptoms of a septic arthritis in both knees and hips and delayed wound healing and fistula formation after implantation of a total hip prosthesis one month before. | Eight day after surgery, the patients presented with left hip pain and clinical signs of infection, including fever (38.5 °C), redness and swelling around the surgical site. And he reported significant local press pain. Approximately 400-ml light yellow, odorless effusion of the wound was drained. |
Antibiotic prevention | Cefazolin | Ceftazidime, vancomycin | Vancomycin | NA | NA | Cefazolin |
Antibiotic treatment. | Cefazolin was replaced by vancomycin. Later transferred to the combination into erythromycin, clindamycin and minocyline. | Vancomycin, metronidazole. | Vancomycin. Later switched to azithromycin, doxycycline, moxifloxacin. | Cefazolin 500 mg of tetracycline iv every 8 h. After the first week, switched to oral doxycycline (200 mg/day), and over the next 3 weeks. | Ciprofloxacin and clindamycin; subsequently changed to cefazolin and clindamycin, continued for 4 weeks; and later changed to moxifloxacin and rifampin for a presumed chronic S. epidermidis infection. Treatment with moxifloxacin was initiated, however the patient’s condition continued to deteriorate. | Cefepime, clindamycin, moxifloxacin, and doxycycline. |
Blood culture | Negative | Negative | Negative | Negative | Negative | Negative |
Outcome | Recovery | Recovery | Recovery | Recovery | Dead | Recovery |
Furthermore, it is difficult to clarify the possible portal of entry of
M. hominis in cases of this postoperative infection [
20]. In accordance with previous reports, the source for an
M. hominis in postoperative hip or joint infections might be explained by seeding of surgical site through transient bacteraemia. This bloodstream infection occurred after urinary catheterization if the genitourinary tract had been colonized by the microorganism. Indeed, urinary tract catheterization has been associated with
mycoplasma bacteraemia leading to the seeding of brain-damaged tissues in brain abscess cases [
5,
6,
9,
21]. Similarly, in our case, a possible pathway might be indwelling catheter used during surgery and a possible route for hematogenous spread to surgical site. However, it is rather difficult to definitively identify the source of infection.
It presented a challenge to identify
M. hominis as pathogen due to its elusiveness and fastidious slow-growing nature [
5,
8,
13,
22,
23]. This might be explained by the following reasons. Firstly,
M. hominis has a 3-layer sterol membrane but lacks cell wall. Consequently, the inability to detect
Mycoplasma spp. by routine gram-staining contributes to the failure of detection in the clinical specimens [
24]. In present case, the gram-staining and Wright-Giemsa mixed staining smear of subcutaneous fluid and the colonies demonstrated no bacterial morphology. Secondly, the slow-growth properties of
M. hominis made the detection on plates challenging, because it generally takes several days (often ≥2 days) to grow into tiny colonies on the media commonly used in laboratory and the requirement for extended incubation period makes a timely diagnosis less likely. And moreover, the routine biochemical methods might fail to identify it correctly [
18]. Thirdly, it is rather difficult to detect the growth of
M. hominis in standard blood culture bottle solutions that use polyanethol sulfonate as an anticoagulant but rather requiring special methods for growth through automatic detection systems in those with suspected bacteremia, and false-negative results are likely yielded [
16‐
19,
24]. Taken together, the post-surgical
M. hominis infection cases are not readily detected via standard microbiology methods [
7,
19]. Considering the high urethral carriage rate of
M. hominis (~ 15% of healthy adults) and catheterization is a common procedure during operation, the possibility of postoperative
Mycoplasma infection might be under-diagnosed or reported [
8].
Our Pubmed review showed that 83.3% (5/6) of the patients survived after appropriate antimicrobial treatment. Furthermore, previous studies demonstrated that the mycoplasmas resulted in serious infections without timely detection [
15,
19,
22]. For example, a patient with implantation of a total hip prosthesis died due to a postoperative hip prosthesis and disseminated infection by
M. hominis and
Ureaplasma parvum [
19]. Accordingly, if a patient developed unexplained post-surgical fever in cases of otherwise culture-negative infections, particularly if treat with wide-spectrum antibiotics meets with a poor response, it is especially important to consider the potential of
Mycoplasmas as pathogens.
Empiric therapy for postoperative infections generally includes agents such as beta-lactams and vancomycin that act on the bacterial cell wall. Such an initial therapy will show no efficacy against
M. hominis infections due to its lack of cell wall [
16,
17]. Furthermore,
M. hominis is, in contrast to most mycoplasmas, intrinsically resistant to currently available macrolide antibiotics due to the mutations in the 23S rRNA gene and is the only mycoplasma susceptible to clindamycin, which often used for eradicating
M. hominis with favorable results [
16]. Quinolones (ciprofloxacin or moxifloxacin) or tetracyclines (minocyline) are active against
M. hominis and moxifloxacin appears to have the greatest activity as the most effective therapeutic agent. If
M. hominis was correctly identified as underlying pathogen, the antibiotics would be therefore switched to the right agents with a marked improvement of clinical syndromes and a favorable result [
16,
19]. The patient in our case had the regimen of the combination of moxifloxacin and doxycycline and had positive response.
In summary, the postoperative infection after hip replacement secondary to M. hominis is rare. Currently there are 4 published reports of septic arthritis caused by M. hominis after hip or knee replacement in adults. Our case added to this body of evidence. The clinicians should recognize the possibility of M. hominis involvement in postoperative infections without microbiological findings or response to standard therapy, and consider changing antibiotic regimen.