The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?
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Abstract
Background
Although sonication is a valuable diagnostic tool for periprosthetic joint infections (PJI), it is not commonly utilized. We analyzed sonicate and intraoperative tissue culture results obtained from three hospitals to define the microbial etiology of PJIs in Korea. Furthermore, we investigated necessity of conducting regular fungal and mycobacterial cultures.Methods
We retrospectively analyzed data for patients with suspected orthopedic-related infections between 2017 and 2022, who had undergone prostheses removal surgery. We included 193 patients with suspected PJIs, and bacterial (n = 193), fungal (n = 193), and mycobacterial (n = 186) cultures were conducted on both sonicate and intraoperative tissue samples. The diagnosis of PJI was based on the European Bone and Joint Infection Society (EBJIS) criteria.Results
Out of 193 patients, 121 (62.7%) had positive sonicate cultures, while 112 (58.0%) had positive periprosthetic tissue cultures. According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI. Among 141 patients, staphylococci were the most common organisms, accounting for 51.8% of cases, followed by Gram-negative organisms (15.6%), fungus (8.5%), and mycobacteria (3.5%). Nearly 91.7% of fungal isolates were Candida species, which also grew in bacterial cultures. In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture. The antibiotic treatment plans were adjusted according to culture results.Conclusions
Utilizing sonicate culture has greatly assisted in identifying pathogens responsible for chronic indolent PJIs, allowing suitable antimicrobial treatment. Based on few cases involving non-Candida and mycobacterial infections, it appears that routine fungal and mycobacterial cultures may not be necessary.Free full text
The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?
Abstract
Background
Although sonication is a valuable diagnostic tool for periprosthetic joint infections (PJI), it is not commonly utilized. We analyzed sonicate and intraoperative tissue culture results obtained from three hospitals to define the microbial etiology of PJIs in Korea. Furthermore, we investigated necessity of conducting regular fungal and mycobacterial cultures.
Methods
We retrospectively analyzed data for patients with suspected orthopedic-related infections between 2017 and 2022, who had undergone prostheses removal surgery. We included 193 patients with suspected PJIs, and bacterial (n = 193), fungal (n = 193), and mycobacterial (n = 186) cultures were conducted on both sonicate and intraoperative tissue samples. The diagnosis of PJI was based on the European Bone and Joint Infection Society (EBJIS) criteria.
Results
Out of 193 patients, 121 (62.7%) had positive sonicate cultures, while 112 (58.0%) had positive periprosthetic tissue cultures. According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI. Among 141 patients, staphylococci were the most common organisms, accounting for 51.8% of cases, followed by Gram-negative organisms (15.6%), fungus (8.5%), and mycobacteria (3.5%). Nearly 91.7% of fungal isolates were Candida species, which also grew in bacterial cultures. In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture. The antibiotic treatment plans were adjusted according to culture results.
Conclusions
Utilizing sonicate culture has greatly assisted in identifying pathogens responsible for chronic indolent PJIs, allowing suitable antimicrobial treatment. Based on few cases involving non-Candida and mycobacterial infections, it appears that routine fungal and mycobacterial cultures may not be necessary.
Introduction
With the growing frequency of orthopedic surgeries, the occurrence of postoperative complications has increased, with infection being the most dreaded among them [1,2]. The rise in periprosthetic joint infection (PJI) caused by hard-to-treat microorganisms like antibiotic-resistant bacteria, fungi, and mycobacteria is imposing major economic burdens [3,4]. Therefore, it is crucial to have a highly reliable diagnosis of PJI and its microbiological epidemiology due to its invasive nature, the long duration of treatment it requires, and the limited options for antimicrobial therapy when dealing with challenging organisms. Extensive research has been conducted on the diagnostic criteria for PJI over the years, and these criteria encompass a combination of clinical, histological, and microbiological data. Notably, the clinical microbiology criteria outlined by various authoritative bodies such as the International Consensus Meeting (ICM) in 2018, the Infectious Disease Society of America (IDSA) in 2013, the American Academy of Orthopedic Surgeons (AAOS) in 2019, and the European Society for Bone and Joint Infections (EBJIS) in 2021 exhibit overlapping aspects, albeit with subtle distinctions [5–9]. Until now, the gold standard for microbiological diagnosis of PJI has been the culture of periprosthetic tissue, but the culture yields from these samples are low, posing a significant challenge in diagnosing PJI [10,11]. Sonication, on the other hand, effectively dislodges biofilms and the bacteria contained within them from the surfaces of implants; [12] hence, the EBJIS includes the culture of explanted prosthesis in their criteria.
The diagnosis of PJI traditionally involved obtaining multiple deep tissue samples during surgery. However, a recent practice has emerged where sonication cultures are used on removed devices [13]. The use of sonicate cultures in clinical microbiology laboratories of tertiary general hospitals is not yet widespread. Orthopedic surgeons often request multiple sets of fungal, mycobacterial, and traditional bacterial cultures. Since the microbial yields from sonicate and tissue samples vary significantly across different medical centers and countries, further research is necessary to investigate the microbiology of PJI and the diagnostic accuracy of sonicate cultures. To address this, we conducted a study examining the results of both sonicate and tissue cultures from three hospitals in Korea. Additionally, we evaluated the diagnostic utility of routine fungal and mycobacterial cultures of sonicate and tissue samples in identifying the cause of PJIs.
Methods
Study design and setting
This retrospective observational study was conducted at Chonnam National University Hospital, Hwasun Chonnam National University Hospital, and Bitgoeul Chonnam National University Hospital. We made the registry of sonicate culture since October 2016. Patients undergoing prostheses removal surgery, whose prostheses were sent for sonication between January 2017 and December 2022, were analyzed. The medical records were abstracted by two of the authors (orthopedic surgeon and infectious disease specialist). Orthopedic prostheses were removed during the diagnosis and treatment steps of one- or two-stage surgery, as well as many other types of surgery. The exclusion criteria were fewer than two tissue samples sent for culture; prostheses not placed in appropriate, sterile plastic containers during transport; and implants subject to contamination during removal, transportation, or laboratory processing.
Patient demographics and comorbidities, operation sites, all previous orthopedic surgical procedures, clinical signs and symptoms, numbers of tissue specimens collected per patient, any use of antibiotics in the 28 days prior to prosthesis removal, and microbiological culture identifications were recorded. The numbers of conventional bacterial, fungal, and mycobacterial cultures performed for each case were examined, and the sensitivity and specificity of the culture rates, as well as the diagnostic performance of each culture type were calculated.
Diagnosis of PJI
We suspected a PJI using modified clinical criteria (excluding microbiological results) used in previous studies [12,14] (S1 Table). Acute PJI refers to the onset of PJ infectious symptoms or signs within 3 months of implantation or surgery. Chronic PJI was characterized by persistent infectious symptoms or signs that typically presented > 3 months postoperatively.
Microbiological diagnoses proceeded as follows. All strains isolated from periprosthetic tissues/pus, synovial fluid, and prosthesis sonicate cultures were recorded. According to the IDSA guidelines [7], when the diagnostic standards for orthopedic infections are met, a virulent microorganism (e.g., Staphylococcus aureus) isolated from even a single specimen is considered to be the causative organism. For low-virulence pathogens and/or potential contaminants such as coagulase-negative staphylococci (CoNS), Corynebacterium species, or Cutibacterium acnes, at least two culture-positive perioperative and preoperative samples were required for diagnosis. We considered a case to be a true fungal or mycobacterial infection if the treating clinician prescribed antifungal or antimycobacterial agents following isolation of a fungal or mycobacterial organism. The sensitivity profiles of all strains were determined as described by the Clinical Laboratory Standards Institute [15]. The diagnostic criteria of the EBJIS, including the microbiological results (S1 Table), were applied for all other assessments [5].
Microbiological procedures
Microbiological studies were performed from preoperative synovial fluid or intraoperative periprosthetic tissue and sonicate fluid. Bacterial culture, fungal culture or mycobacterial culture of each specimen were ordered. In the laboratory, samples for bacterial culture were inoculated onto blood agar plates (BAPs), chocolate agar plates, and MacConkey agar plates in jars at 35°C, and also into anaerobic thioglycolate broth. The agar plates were incubated at 35–37°C for 5 days aerobically and 14 days anaerobically. Thioglycollate broths were incubated for 14 days at 35–37°C; in the event of bacterial growth (turbidity), the liquid was seeded onto BAPs (both aerobic and anaerobic cultures). Saboured dextrose agar and potato dextrose agar plates were used for fungal culture. For mycobacterial culture, pretreated samples were inoculated into mycobacterium growth indicator tubes (MGIT), incubated in the MGIT 960 device for 1 week, and then cultured for 6 weeks. The samples were also inoculated into 3% (w/v) Ogawa medium, incubated for 1 week, and then cultured for 6 weeks.
1) Preoperative synovial fluid culture
0.1 mL of synovial fluid was inoculated onto plates and into thioglycolate broth, and aerobic and anaerobic growth assessed.
2) Intraoperative periprosthetic tissue cultures
The surgeon selected several representative tissue samples from the surgical field; most were inflamed or purulent. A complete bacterial and fungal culture setup included five aerobic agar plates, one enrichment broth, three anaerobic agar plates, a gram stain, and a KOH stain. At least two complete culture setups were ordered for each patient. The evaluation of up to eight additional bacteria and fungi was possible at the physician’s discretion. Mycobacterial culture and MTB-PCR hybridization were added if the surgeon so requested.
3) Sonicate cultures
Prostheses explanted during surgical procedures were processed using the Mayo Clinic protocol [16,17]. The prostheses were placed in sterile containers with 400 mL of Ringer’s solution. After vortexing for 30 s, the containers were sonicated at 40 kHz for 5 min, followed by vortexing for a further 30 s. The sonication fluid was transferred to a 50-mL tube and centrifuged for 5 min. The supernatant was removed and aliquots of 0.1 mL inoculated onto aerobic and anaerobic BAPs (0.1 mL inoculum equals 10 mL of the original sonicated sample). Sonicate cultures were cultured at 35–37°C for 5 days aerobically and 14 days anaerobically, and the numbers and identities of all colonies recorded. If a specimen contained ≥ 5 colony-forming units (CFU) of any organism, identification and susceptibility tests were performed. For sonicate fluids, we considered that a culture was positive if growth exceeded 20 CFU/10 mL according to mayo clinic protocol [18], with the exception of virulent microorganisms such as S. aureus, for which any growth was considered positive. The complete bacterial culture setup included two BAPs per sonication fluid. Additional culture workups for fungi or mycobacteria were at the surgeon’s discretion (no guidelines).
Statistical analyses
The baseline characteristics of all groups were compared using the chi-squared test. All calculations were performed using the SPSS v28 statistical software package (SPSS Inc., Chicago, IL, USA) and R v4.3.2 (R Core Team, Vienna, Austria).
Ethics statement
The present study protocol was reviewed and approved by the Institutional Review Board of Chonnam National University Hospital (approval No. 2023–091) and the need for informed consent was waived.
Results
Study population
During the study period, 333 patients underwent orthopedic implant removal for various reasons including suspected PJI, aseptic loosening, or fixation failure. Revision surgeries after treatment to rule out persistent infections were excluded (Fig 1). Of the 333 patients, 193 undergoing revisions because of suspected prosthetic hip or knee joint infections and whose removed prostheses underwent appropriate sonicate and tissue cultures were included. Fungal tissue cultures were performed for all 193 patients and mycobacterial cultures for 186 patients.
Table 1 lists the patient characteristics. Overall, the median age was 71.2 years and 46.6% were male. Patients with knee prostheses comprised 55.4% of all cases and preoperative antibiotics were administered to 46.1% of the 193 cases. A total of 162 patients (83.9%) had chronic PJIs. Prosthesis removal during a two-stage exchange operation was the most common form of retrieval. Preoperative synovial fluids were cultured for 137 patients; 64 were positive. Sonicate cultures were positive in 121 of the 193 patients (62.7%) and intraoperative tissue cultures were positive in 112 (58.0%). Each patient yielded between two and eight tissue culture samples (median 3.69 samples) and 28.5% more than five. When the modified clinical criteria were applied, 183 were diagnosed with PJI. Of all patients assessed, 93.8% (181/193) were diagnosed with PJIs using the EBJIS criteria. Fig 1 show inclusion criteria and number of microbiologically confirmed cases including preoperative synovial fluid culture.
Table 1
| Characteristic | Value | n (%) |
|---|---|---|
| Mean age, years (range) | 71.2 (42.0–89.0) | 193 |
| Sex | Male | 90 (46.6) |
| Sinus tract status | Present | 27 (14) |
| Visual purulence | Present | 175 (90.7) |
| Permanent biopsy, n = 76 | Neutrophil≥5/HPF | 56 (73.6) |
| Frozen biopsy, n = 50 | Neutrophil≥5/HPF | 32 (64) |
| Site of arthroplasty | Hip | 86 (44.6) |
| Knee | 107 (55.4) | |
| Preoperative antimicrobial use within 28 days | Yes | 89 (46.1) |
| Acute/chronic PJI | Acute | 31 (16.1) |
| Chronic | 162 (83.9) | |
| Operation type | Debridement and implant retention | 20 (10.4) |
| One-stage exchange | 13 (6.7) | |
| Two-stage exchange | 153 (79.3) | |
| Girdlestone operation | 6 (3.1) | |
| Arthrodesis | 1 (0.5) | |
| Serum C-reactive protein, mg/dL | > 10 | 42 (21.8) |
| 1–10 | 125 (64.8) | |
| ≤ 1 | 26 (13.5) | |
| Erythrocyte sedimentation rate, mm/h, n = 182 | > 30 | 159 (87.4) |
| ≤ 30 | 23 (12.6) | |
| Preoperative synovial fluid culture, n = 137 | Positive | 64 (46.7) |
| Intraoperative tissue culture, n = 193 | Positive | 112 (58.0) |
| Intraoperative sonicate fluid culture, n = 193 | Positive | 121 (62.7) |
| Number of periprosthetic tissue samples taken | ≥ 5 | 55 (28.5) |
| 2–4 | 138 (71.5) | |
| 2021 EBJIS Criteria | Confirmed and likely | 181 (93.8) |
| Unlikely | 12 (6.2) |
n, number; EBJIS, European Bone and Joint Infection Society.
Microbiological assessment
Table 2 lists the microbiological results for 181 patients with PJI diagnoses using the 2021 EBJIS criteria. A total of 141 patients was microbiologically confirmed. A total of 112 patients (61.9%) yielded positive tissue cultures and 121 (66.9%) positive sonicate cultures. In most cases, only one strain was identified as a causative organism. The most commonly cultivated organisms were staphylococci (51.8%), followed by Gram-negative organisms (15.6%). In terms of CoNS, the sonicate cultures yielded more positive results than did tissue cultures (27.6% vs. 21.0%), but S. aureus was more frequently detected in tissue culture. Of Gram-negative organisms, Escherchia coli was the most common; sonicate cultures were more often positive than others. Pseudomonas aeruginosa was detected at a higher rate in tissue culture. Twelve Candida species and one mold grew in culture. When acute and chronic PJI were analyzed separately, CoNS and E. coli were detected more frequently in sonicate cultures from patients with chronic PJIs.
Table 2
|
Synovial fluid
(n = 132) | Total (n = 181) | Acute/Chronic PJI | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Acute PJI (n = 28) | Chronic PJI (n = 153) | |||||||||||||
| Microbiology | n | % | Tissue | Sonicate | Tissue | Sonicate | Tissue | Sonicate | ||||||
| n | % | n | % | n | % | n | % | n | % | n | % | |||
| Number of detected organisms (n = 141) | 64 | 112 | 121 | |||||||||||
| Bacteria | ||||||||||||||
| 18 | 13.6% | 21 | 11.6% | 18 | 9.9% | 3 | 10.7% | 2 | 7.1% | 18 | 11.8% | 16 | 10.5% | |
| 12 | 9.1% | 29 | 16.0% | 37 | 20.4% | 3 | 10.7% | 3 | 10.7% | 26 | 17.0% | 34 | 22.2% | |
| 5 | 3.8% | 9 | 5.0% | 13 | 7.2% | 1 | 3.6% | 2 | 7.1% | 8 | 5.3% | 11 | 7.2% | |
| 1 | 0.8% | 2 | 1.1% | 4 | 2.2% | - | - | 1 | 3.6% | 2 | 1.3% | 3 | 2.0% | |
| 2 | 1.5% | 4 | 2.2% | 4 | 2.2% | - | - | - | - | 4 | 2.6% | 4 | 2.6% | |
| - | - | 4 | 2.2% | 4 | 2.2% | 1 | 3.6% | 1 | 3.6% | 3 | 2.0% | 3 | 2.0% | |
| 3 | 2.3% | 2 | 1.1% | 3 | 1.7% | - | - | - | - | 2 | 1.3% | 3 | 2.0% | |
| 1 | 0.8% | 1 | 0.6% | 1 | 0.6% | - | - | - | - | 1 | 0.7% | 1 | 0.7% | |
| - | - | 2 | 1.1% | 2 | 1.1% | - | - | - | - | 2 | 1.3% | 2 | 1.3% | |
| - | - | 1 | 0.6% | 1 | 0.6% | - | - | - | - | 1 | 0.7% | 1 | 0.7% | |
| 1 | 0.8% | 1 | 0.6% | 1 | 0.6% | - | - | - | - | 1 | 0.7% | 1 | 0.7% | |
| 8 | 6.1% | 10 | 5.5% | 13 | 7.2% | 2 | 7.1% | 3 | 10.7% | 8 | 5.2% | 10 | 6.5% | |
| - | - | 1 | 0.6% | 1 | 0.6% | - | - | - | - | 1 | 0.7% | 1 | 0.7% | |
| - | - | - | - | 1 | 0.6% | - | - | - | - | - | - | 1 | 0.7% | |
| 1 | 0.8% | - | - | - | - | - | - | - | - | - | - | - | - | |
| 1 | 0.8% | - | - | - | - | - | - | - | - | - | - | - | - | |
| - | - | 4 | 2.2% | 2 | 1.1% | 1 | 3.6% | 0 | 0.0% | 3 | 2.0% | 2 | 1.3% | |
| - | - | 1 | 0.6% | 1 | 0.6% | 1 | 3.6% | 1 | 3.6% | 1 | 0.7% | 1 | 0.7% | |
| - | - | 1 | 0.6% | 1 | 0.6% | - | - | - | - | - | - | - | - | |
| Fungi | ||||||||||||||
| 1 | 0.8% | 4 | 2.2% | 3 | 1.7% | 2 | 7.1% | 1 | 3.6% | 2 | 1.3% | 2 | 1.3% | |
| 2 | 1.5% | 4 | 2.2% | 3 | 1.7% | - | - | - | - | 4 | 2.6% | 3 | 2.0% | |
| 1 | 0.8% | 1 | 0.6% | 2 | 1.1% | - | - | - | - | 1 | 0.7% | 2 | 1.3% | |
| 1 | 0.8% | 1 | 0.6% | 1 | 0.6% | - | - | - | - | 1 | 0.7% | 1 | 0.7% | |
| Mycobacterium species (n = 4) | ||||||||||||||
| 2 | 1.5% | 2 | 1.1% | - | - | - | - | - | - | 2 | 1.3% | - | - | |
| 1 | 0.8% | 0 | 0.0% | 1 | 0.6% | - | - | - | - | - | - | 1 | 0.7% | |
| - | - | 1 | 0.6% | - | - | - | - | - | - | 1 | 0.7% | - | - | |
| Polymicrobial infection (n = 8) | 3b | 2.3% | 6c | 3.3% | 4d | 2.2% | 2 | 7.1% | - | - | 4 | 2.6% | 4 | 2.6% |
| No pathogen detected (n = 40) | 68 | 51.5% | 69 | 38.1% | 60 | 33.1% | 12 | 42.9% | 14 | 50.0% | 57 | 37.3% | 46 | 30.1% |
n, number; EBJIS, European Bone and Joint Infection Society; PJI, Periprosthetic Joint Infection.
aOne C. parapsilosis was cultured with K. pneumoniae in synovial fluid and one C. parapsilosis was cultured in synovial fluid, tissue, sonicate.
bK. pneumoniae + E. cloacae, P. aeruginosa + A. baumannii, C.parapsilosis + E. faecalis + S. aureus.
cK. pneumoniae + E. cloacae, S. dysgalactiae + S. agalactiae, S. gordonii + S. mitis/oralis, E. faecalis + K. oxytoca, Staphylococcus lugdunensis + E. faecalis, C. striatum + M. fortuitum.
dK. pneumoniea + E. cloacae, S. dysgalactiae + S. agalactiae, S. gordonii + S. mitis/oralis, E. faecalis + K. oxytoca.
Table 3 lists cases for which the results differed between periprosthetic tissue and sonicate cultures. Twenty PJIs were detected by sonication fluid cultures but not tissue cultures, and the antibiotic regimens were changed to reflect the sonicate culture results. Among 20 cases, 16 cases were patients with an isolated positive sonicate culture. The sensitivity increased when sonicate culture were combined with intraoperative tissue or preoperative synovial fluid cultures. Eleven cases were only tissue-culture positive. Two patients were diagnosed with polymicrobial infections via tissue culture.
Table 3
| Case classifications | Periprosthetic tissue culture organisms | Sonicate culture organisms | No. cases | An isolated positive culturea |
|---|---|---|---|---|
| Positive sonicate cultures and negative periprosthetic tissue cultures (n = 20) | – | Staphylococcus epidermidis | 8 | 7 |
| – | Coagulase-negative staphylococci | 3 | 2 | |
| – | Corynebacterium striatum | 1 | 1 | |
| – | Streptococcus agalactiae | 1 | 1 | |
| – | Escherichia coli | 3 | 2 | |
| – | Enterobacter aerogenes | 1 | 1 | |
| – | Candida albicans | 1 | 1 | |
| – | Candida pelliculosa | 1 | 1 | |
| – | Mycobacterium fortuitum | 1 | 0 | |
| Negative sonicate cultures and positive periprosthetic tissue cultures (n = 11) | Staphylococcus aureus | – | 3 | 0 |
| Pseudomonas aeruginosa | – | 2 | 2 | |
| Candida albicans | – | 2 | 1 | |
| Candida parapsilosis | – | 1 | 1 | |
| Mycobacterium tuberculosis | – | 2 | 0 | |
| Mycobacterium terrae complex | – | 1 | 1 | |
| Discordant (positive) sonicate cultures and periprosthetic tissue cultures (n = 2) | Staphylococcus lugdunensis + Enterococcus faecalis | S. lugdunensis | 1 | - |
| C. striatum + M. fortuitum | C. striatum | 1 | - |
aAn isolated positive culture means positive culture results in exclusively sonicate or tissue culture.
Fungal and mycobacterial cultures
A total of 713 conventional bacterial cultures, 713 fungal stain/cultures, and 331 mycobacterial cultures from the intraoperative tissues of 193 patients with suspected PJIs were performed. The test positivity rates of fungal and mycobacterial cultures were 2.95% (21/713) and 3.02% (10/331) respectively. Thirteen cultures were confirmed to be true fungal infections. Surgeons wrote fungal culture orders for synovial fluids (n = 137 patients, 232 fungal cultures) and sonicate fluids (n = 193 patients, 113 fungal cultures). Of five patients with mycobacterial infections, mycobacteria grew in four mycobacterial cultures. Table 4 lists the true fungal PJI culture results. Candida species were predominant; all fungal pathogens grew in bacterial cultures and there were only three positive fungal staining results. In 3 out of 5 cases in which mycobacteria were identified and in 7 out of 13 cases in which fungus was identified, multiple revision operations were performed.
Table 4
| Case no. | Causative organism | Synovial fluid cultures | Periprosthetic tissue cultures | Sonicate cultures | |||
|---|---|---|---|---|---|---|---|
| Positive culture no./no. of bacterial cultures | Positive culture no./no. of fungal cultures | Positive culture no./no. of bacterial cultures | Positive culture no./no. of fungal cultures | Positive culture no./no. of bacterial cultures | Positive culture no./no. of fungal cultures | ||
| 1 | Candida albicans | 0/1 | 0/1 | 2/4 | 2/4 | 0/1 | 0/1 |
| 2 | Candida albicans | – | – | 2/2 | 2/2 | 1/1 | 1/1 |
| 3 | Candida albicans | – | – | 1/2 | 1/2 | 1/1 | - |
| 4 | Candida albicans | – | – | 0/3 | 0/3 | 1/1 | 0/1 |
| 5 | Candida albicans | 1/1 | 0/1 | 2/2 | 0/2 | 0/1 | 0/1 |
| 6 | Candida parapsilosis | 0/1 | 0/1 | 1/2 | 1/2 | 0/1 | - |
| 7 | Candida parapsilosis | 0/1 | 0/1 | 2/3 | 2/3 | 1/1 | - |
| 8 | Candida parapsilosis | 1/2 | 2/2 | 3/4 | 3/4 | 1/1 | 1/1 |
| 9 | Candida pelliculosa | 1/3 | 2/2 | 2/6 | 4/6 | 1/1 | - |
| 10 | Candida pelliculosa | 0/2 | 0/2 | 0/5 | 0/5 | 1/1 | - |
| 11 | Lomentospora prolificans | 1/3 | 1/3 | 1/4 | 2/4 | 1/1 | - |
| 12 | Polymicrobial infection a | 0b/2 | 2c/2 | 4c/4 | 4c/4 | 1/1 | 1/1 |
| 13 | Polymicrobial infection d | 2/3 | 2/3 | 0/4 | 0/4 | 0/1 | 0/1 |
no, number.
aKlebsiella pneumoniae, C. parapsilosis.
bK. pneumoniae was cultured in one of two paired bacterial cultures.
cC. parapsilosis.
dEnterococcus faecalis, Staphylococcus aureus, C. parapsilosis.
Discussion
We analyzed 193 patients whose prostheses were removed because of suspected hip or knee infections. Of all patients assessed, 93.8% (181/193) were diagnosed with PJIs using the EBJIS criteria. Among microbiologically confirmed 141 PJI cases, the most common organisms were staphylococci (51.8%) and Gram-negative organisms constituted 15.6% of all pathogens. Sonicate fluid cultures detected 20 microorganisms that did not grow in periprosthetic tissue cultures. The 13 fungal pathogens all grew in bacterial cultures. Only five patients had mycobacterial infections.
CoNS were frequently detected in sonicate cultures; most PJI CoNS infections were chronic. The ability of bacteria to form biofilms on the surfaces of prostheses contributes greatly to chronic PJI and is one of the main causes why intraoperative tissue samples are often not positive [19]. Ultrasound-mediated dislodgement of biofilms from the surfaces of removed prostheses increases the sensitivities of microbiological studies that seek to identify underlying pathogens [20,21]. Here, S. aureus and P. aeruginosa were detected more frequently in tissue culture, perhaps because these organisms are both more virulent than others and invasive. However, intraoperative tissue cultures alone are compromised by high rates of contamination and thus false-positive results [22]. Generally, microbiology laboratories report only positive or negative growth; quantitation is lacking. When normal skin flora such as CoNS and Corynebacterium species are identified in preoperative synovial fluid or periprosthetic tissue culture, sonicate culture aids pathogen identification by yielding quantitative information.
Although sonication is technically simple, most microbiology laboratories of Korean hospitals do not yet perform sonication cultures. We found that combined sonicate, intraoperative tissue, and synovial fluid cultures increased sensitivity. When a consensus is reached to the effect that isolation of phenotypically identical microorganisms from more than one culture is the gold standard for PJI diagnosis, sonicate culture should be included in PJI diagnosis in Korea.
Most PJIs are caused by bacteria [23,24]. The ICM guideline recommends both fungal and mycobacterial cultures for immunocompromised patients, those with previously confirmed infections, and arthroplasty patients with culture-negative joints [25]. Tai et al. [26] prepared indications for fungal culture when diagnosing PJIs. These include immunocompromised patients (i.e., those undergoing solid organ or hematopoietic stem cell transplantation, patients with AIDS, and cancer patients on active chemotherapy); patients with a history of fungal or mycobacterial PJI; a PJI in a setting of a disseminated fungal or mycobacterial infection; and recurrent culture-negative PJI despite the use of appropriate bacterial culture techniques and adequate treatment. We found that orthopedic surgeons routinely ordered fungal cultures and fungal staining of intraoperative tissues, synovial fluids, or sonicates. In the present study, patients with true fungal PJIs were immunocompetent, but Candida species were readily detected on bacterial culture and only three positive fungal staining results were noted. Such staining should be discouraged when diagnosing PJI; more research on the specific diagnostic evaluation of non-candidal fungal PJIs is needed.
Tuberculosis is common in Korea; [27] mycobacterial culture may be necessary depending on the clinical course of the patient. In this study, only five cases had mycobacterial infections, but surgeons ordered mycobacterial cultures for > 96% of suspected PJI patients. Routine performance of specialized cultures increases the financial burden on patients and incurs unnecessary medical expenses [28,29]. Any need for such cultures should be carefully considered on the basis of the risk factors, patient history, and clinical progress in the detection of culture-negative PJIs.
Our work had several limitations. First, the overall culture sensitivity was lower than those of other studies [12,13,30,31]. In our work, about 46% of patients received antibiotics treatment before operation and 70% of patients yielded ≤ 4 tissue samples. Some tissue samples were obtained after irrigation of wounds or deeper tissues. Such variations are inevitable in any retrospective study. Second, we included both hip and knee PJIs. Third, some serum biomarker and synovial fluid data required for PJI diagnosis were missing. Forth, we recorded only a few true mycobacterial PJI and mold infections. More clinical research on hard-to-treat microorganisms is required; specific diagnostic evaluations are needed. Lastly, there were 16 cases with an isolated positive sonicate culture and a significant number were low virulent microorganisms in our work. Although Rondaan C, et al. recently, reported the clinical relevance of an isolated positive sonicate culture [32], these findings require further exploration for clinical importance.
Conclusions
In summary, a combination of periprosthetic tissue, sonicate, and synovial fluid cultures improved PJI pathogen identifications and will aid the choice of appropriate antibiotics. Sonicate culture is simple; general laboratories should add this valuable technique to the microbiological diagnosis of PJIs in Korea. Candida infections were well detected in bacterial cultures. Fungal staining/culture and mycobacterial culture are of little use in terms of PJI diagnosis; fungal and mycobacterial cultures may be required when indicated.
Supporting information
S1 Table
Diagnostic criteria for hip or knee periprosthetic joint infection.(DOCX)
Acknowledgments
We wish to thank participating care units for their collaboration in the realization of this study.
Funding Statement
This work was supported by the Chonnam National University Hospital Biomedical Research Institute (BCR124055) and GIST-CNUH research collaboration grant (BCR122060). The funding sources had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Data Availability
The data are available from the Harvard Dataverse database (https://doi.org/10.7910/DVN/QNL0WW).
References
Decision Letter 0
24 Mar 2024
PONE-D-24-06916The microbiology of prosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?PLOS ONE
Dear Dr. Park,
Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.
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PLOS ONE
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Reviewer #1: Partly
Reviewer #2: Yes
**********
2. Has the statistical analysis been performed appropriately and rigorously?
Reviewer #1: N/A
Reviewer #2: Yes
**********
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Reviewer #1: No
Reviewer #2: Yes
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Reviewer #2: No
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5. Review Comments to the Author
Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)
Reviewer #1: This is an important topic especially since we need a diverse voice in Ortho research. However, it needs further work before being ready for publication.
Major comments:
1. It’s confusing what are the primary objectives of this study. It seems like it is focusing on the performance and results of sonicate cultures, fungal and mycobacterial cultures. However, it also talks about the overall microbiology of PJI in Table 2, then sensitivity/specificity of microbiologic testing in Table 4. I recommend focusing on the paper on sonicate culture, fungal and mycobacterial culture results. For the gold standard, the authors could focus on EBJIS criteria instead of adding the ICM criteria. The accuracy of synovial and periprosthetic tissue cultures is another broad topic which can be addressed using another strategy and not appropriate to be linked to this paper.
Minor comments:
1. Recommend editing Introduction and abstract to be more general in nature for broader readership rather than focusing on Korea. Suggest, “The use of sonicate cultures in clinical microbiology laboratories of tertiary general hospitals is not yet widespread. Orthopedic surgeons often request multiple sets of fungal, mycobacterial, and traditional bacterial cultures. Since the microbial yields from sonicate and tissue samples vary significantly across different medical centers and countries, further research is necessary to investigate the microbiology of PJI and the effectiveness of sonicate cultures”
2. Edit terms “staphylococci” – Small letter s, not capital. “Gram-negative”- Capital letter G.
3. Harmonize "periprosthetic joint infections" instead of "prosthetic"
4. Sonication was not part of the IDSA diagnostic criteria, please revise.
5. Recommend changing term, “efficacy” to “accuracy” and “utility” in introduction. Diagnostic tests are not judged based on efficacy. It’s a term for therapeutic tests.
Reviewer #2: The manuscript titled "The microbiology of prosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?" focuses on interesting topic. I commend the authors for their dedication and express my appreciation for the chance to evaluate their manuscript. The manuscript is crafted in a decent manner, that can in terms on English be also improved. Congratulations to the authors on their findings. A retrospective multi-centre study that in my opining should be taken into consideration to be published after a revision. The conclusions are consistent with the evidence and arguments presented and effectively address the main question posed.
After assessing the manuscript, the following issues raised my concerns or represent suggestions that from my point of view can increases the overall quality of the manuscript:
- Abstract – results – “According to EBJIS criteria, total of 181 patients were diagnosed with acute (28 patients) or chronic (153 patients) PJIs” – The EBJIS criteria represent a set of definition criteria for periprosthetic joint infections (PJIs), whereas in 2004 for e.g., Zimmer et al proposed a classification system for PJIs, which was subsequently published in the New England Journal of Medicine. It is important to note that while the EBJIS criteria serve to define PJIs, the classification system proposed by Zimmer et al categorizes PJIs into distinct groups based on their clinical presentation and various other factors. Please also note the statements of the authors of the EBJIS criteria “This definition does not distinguish PJI on the basis of the duration of the infection (acute or chronic) or the time of onset from implantation (early or late). These terms are not defined with any degree of certainty with time-dependant cut-offs, and so cannot be included in a definition of PJI.”
- Abstract – “In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture.” What is your approach in cases of only positive sonication fluid cultures? As a suggestion – take a look at this multicenter retrospective cohort study - Rondaan C, Maso A, Birlutiu RM, Fernandez Sampedro M, Soriano A, Diaz de Brito V, Gómez Junyent J, Del Toro MD, Hofstaetter JG, Salles MJ, Esteban J, Wouthuyzen-Bakker M; ESCMID Study Group on Implant Associated Infections (ESGIAI). Is an isolated positive sonication fluid culture in revision arthroplasties clinically relevant? Clin Microbiol Infect. 2023 Jul 28:S1198-743X(23)00345-2. 10.1016/j.cmi.2023.07.018. Epub ahead of print. PMID: 37516385.
- Diagnosis of PJIs- “To evaluate the diagnostic utility of periprosthetic tissue and sonicate cultures, PJIs were diagnosed using modifications of clinical criteria (excluding microbiological results) used in previous studies [12, 16].” Do you have some internal validation study for this criteria?
- Sonication cultures – “For sonicate fluids, we considered that a culture was positive if growth exceeded 20 CFU/10 mL, with the exception of virulent microorganisms such as S. aureus, for which any growth” – Based on this and having in mind the EBJIS criteria, in your study a positive culture = 2CFU/ml – for a confirmed infection >50CFU/ml are needed and for likely > 1 CFU/ml. Also the authors of the EBJIS criteria report “Any positive culture from sonication fluid must be considered as a potential infection, but > 50 colony-forming units/ml (CFU/ml) confirms infection. The proposed cut-offs refer to a non-concentrated technique. If the concentration technique is applied, the suggested cut-off is 200 CFU/ml to confirm an infection. If other variations to the protocol are used, validated cut-offs for each protocol must be applied.”
- “removal of orthopedic implants for any reason.” Also “microbes” - Please rephrase in an more academic manner
- “By the 2021 EBJIS criteria, the most common organisms were Staphylococcus (51.8%) and gram-negative organisms constituted 15.6% of all pathogens.” As a personal opinion, the sentence should be rephrased to avoid confusion. Some might think that the EBJIS criteria are also criteria for the pathogens.
- Could you please confirm if there have been multiple revisions related to prosthetic joint infection caused by fungi or mycobacteria?
- “received antibiotics before operation” – as a treatment or perioperative prophylaxis?
**********
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Reviewer #1: No
Reviewer #2: No
**********
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Author response to Decision Letter 0
27 May 2024
Title: The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?
Dear Editor-in-Chief
I would like to thank you for giving us the opportunity to revise our work. We have revised the manuscript in light of the valuable suggestions, and we believe it has been greatly improved. Attached you will find our revised manuscript, as well as our responses to the comments. This manuscript has not been published in any journal and is not under consideration for publication elsewhere. All authors including myself have seen and approved this manuscript.
Again, we thank you and the reviewers for a constructive and helpful review.
Here are the detailed descriptions
Sincerely yours,
Kyung-Hwa Park
Department of Infectious diseases,
Chonnam National University Medical School
42 Jebong-ro, Dong-gu, Gwangju, 61469, Korea
Responses to comments:
Comments:
Reviewer #1: This is an important topic especially since we need a diverse voice in Ortho research. However, it needs further work before being ready for publication.
Major comments:
1. It’s confusing what are the primary objectives of this study. It seems like it is focusing on the performance and results of sonicate cultures, fungal and mycobacterial cultures. However, it also talks about the overall microbiology of PJI in Table 2, then sensitivity/specificity of microbiologic testing in Table 4. I recommend focusing on the paper on sonicate culture, fungal and mycobacterial culture results. For the gold standard, the authors could focus on EBJIS criteria instead of adding the ICM criteria. The accuracy of synovial and periprosthetic tissue cultures is another broad topic which can be addressed using another strategy and not appropriate to be linked to this paper.
→ We agree with reviewer’s comment absolutely. As recommended, we focused on results of sonicate cultures, fungal and mycobacterial cultures. Related paragraphs regarding the sensitivity/specificity of microbiological tests and Table 4 were deleted in method and results section of revised manuscript. Also, we focused EJBIS criteria and removed ICM criteria in the revised manuscript.
Minor comments:
1. Recommend editing Introduction and abstract to be more general in nature for broader readership rather than focusing on Korea. Suggest, “The use of sonicate cultures in clinical microbiology laboratories of tertiary general hospitals is not yet widespread. Orthopedic surgeons often request multiple sets of fungal, mycobacterial, and traditional bacterial cultures. Since the microbial yields from sonicate and tissue samples vary significantly across different medical centers and countries, further research is necessary to investigate the microbiology of PJI and the effectiveness of sonicate cultures”
→ As recommended, we have changed the description of the abstract and introduction section of revised manuscript.
2. Edit terms “staphylococci” – Small letter s, not capital. “Gram-negative”- Capital letter G.
→ As recommended, capitalization errors in the revised manuscript were changed.
3. Harmonize "periprosthetic joint infections" instead of "prosthetic"
→ As you recommended, we harmonized the terms to “periprosthetic joint infection.
4. Sonication was not part of the IDSA diagnostic criteria, please revise.
→ As recommended, we have changed the description of the introduction section of revised manuscript.
5. Recommend changing term, “efficacy” to “accuracy” and “utility” in introduction. Diagnostic tests are not judged based on efficacy. It’s a term for therapeutic tests.
→ As recommended, we have changed the terms of the introduction section of revised manuscript.
Reviewer #2:
The manuscript titled "The microbiology of prosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?" focuses on interesting topic. I commend the authors for their dedication and express my appreciation for the chance to evaluate their manuscript. The manuscript is crafted in a decent manner,that can in terms on English be also improved. Congratulations to the authors on their findings. A retrospective multi-centre study that in my opining should be taken into consideration to be published after a revision. The conclusions are consistent with the evidence and arguments presented and effectively address the main question posed.
After assessing the manuscript, the following issues raised my concerns or represent suggestions that from my point of view can increases the overall quality of the manuscript:
1. Abstract – results – “According to EBJIS criteria, total of 181 patients were diagnosed with acute (28 patients) or chronic (153 patients) PJIs” – The EBJIS criteria represent a set of definition criteria for periprosthetic joint infections (PJIs), whereas in 2004 for e.g., Zimmer et al proposed a classification system for PJIs, which was subsequently published in the New England Journal of Medicine. It is important to note that while the EBJIS criteria serve to define PJIs, the classification system proposed by Zimmer et al categorizes PJIs into distinct groups based on their clinical presentation and various other factors. Please also note the statements of the authors of the EBJIS criteria “This definition does not distinguish PJI on the basis of the duration of the infection (acute or chronic) or the time of onset from implantation (early or late). These terms are not defined with any degree of certainty with time-dependent cut-offs, and so cannot be included in a definition of PJI.”
→ We agree with reviewer’s comment absolutely. As recommended, we have changed the abstract of revised manuscript.
“According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI.”
2. Abstract – “In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture.” What is your approach in cases of only positive sonication fluid cultures? As a suggestion – take a look at this multicenter retrospective cohort study - Rondaan C, Maso A, Birlutiu RM, Fernandez Sampedro M, Soriano A, Diaz de Brito V, Gómez Junyent J, Del Toro MD, Hofstaetter JG, Salles MJ, Esteban J, Wouthuyzen-Bakker M; ESCMID Study Group on Implant Associated Infections (ESGIAI). Is an isolated positive sonication fluid culture in revision arthroplasties clinically relevant? Clin Microbiol Infect. 2023 Jul 28:S1198-743X(23)00345-2. 10.1016/j.cmi.2023.07.018. Epub ahead of print. PMID: 37516385.
→ Thank you for your kind comment. According to EBJIS criteria, we included an isolated positive sonicate culture pathogen. Among 20 cases cultured positive only in sonicate culture (not tissue), there were 16 cases with an isolated sonicate culture. We added this data in the results section of revised manuscript and Table 3.
“Among 20 cases, 16 cases were patients with an isolated positive sonicate culture”.
We discussed this as limitation in the discussion section of the revised manuscript..
→ Lastly, there were 16 cases with an isolated positive sonicate culture and a significant number were low virulent microorganisms in our work. Although Rondaan C, et al. recently reported the clinical relevance of an isolated positive sonicate culture [32], these findings require further exploration for clinical importance.
3. Diagnosis of PJIs- “To evaluate the diagnostic utility of periprosthetic tissue and sonicate cultures, PJIs were diagnosed using modifications of clinical criteria (excluding microbiological results) used in previous studies [12, 16].” Do you have some internal validation study for this criteria?
→ This registry is part of an ongoing cohort study for sonicate culture that began in 2016. The medical records were abstracted by two of the authors (orthopedic surgeon and infectious disease specialist). Although we did not validate this criteria internally, our data were reviewed by each specialists.
We added these sentences in study design in the method section of revised manuscript.
“We made the registry of sonicate culture since October 2016. Patients undergoing prostheses removal surgery, whose prostheses were sent for sonication between January 2017 and December 2022, were analyzed. The medical records were abstracted by two of the authors (orthopedic surgeon and infectious disease specialist).”
4. Sonication cultures – “For sonicate fluids, we considered that a culture was positive if growth exceeded 20 CFU/10 mL, with the exception of virulent microorganisms such as S. aureus, for which any growth” – Based on this and having in mind the EBJIS criteria, in your study a positive culture = 2CFU/ml – for a confirmed infection >50CFU/ml are needed and for likely > 1 CFU/ml. Also the authors of the EBJIS criteria report “Any positive culture from sonication fluid must be considered as a potential infection, but > 50 colony-forming units/ml (CFU/ml) confirms infection. The proposed cut-offs refer to a non-concentrated technique. If the concentration technique is applied, the suggested cut-off is 200 CFU/ml to confirm an infection. If other variations to the protocol are used, validated cut-offs for each protocol must be applied.”
→ Thank you for kind comment. We would like to quote the following paper published recently- Alvarez Otero J, Karau MJ, Greenwood-Quaintance KE, Abdel MP, Mandrekar J, Patel R. Evaluation of Sonicate Fluid Culture Cutoff Points for Periprosthetic Joint Infection Diagnosis. In Open Forum Infectious Diseases 2024 Mar 20 (p. ofae159). This study discussed ideal sonicate fluid culture cutoff points for PJI diagnosis and concluded that 20 CFU/10ml was appropriate for the diagnosis of hip and knee PJI according to Mayo Clinic protocol.
→ Because we used Mayo Clinic protocol and considered 20 CFU/10ml as validated cut-offs, we added this as reference in the method of revised manuscript and mentioned this in S1 Table.
5. “removal of orthopedic implants for any reason.” Also “microbes” - Please rephrase in a more academic manner
→ As recommended, we have changed the description of the methods section of revised manuscript. We have changed microbes into microorganisms.
“During the study period, 333 patients underwent orthopedic implant removal for various reasons including suspected PJI, aseptic loosening, or fixation failure.”
6. “By the 2021 EBJIS criteria, the most common organisms were Staphylococcus (51.8%) and gram-negative organisms constituted 15.6% of all pathogens.” As a personal opinion, the sentence should be rephrased to avoid confusion. Some might think that the EBJIS criteria are also criteria for the pathogens.
→ As recommended, we have rephrased the sentence.
“Among microbiologically confirmed 141 PJI cases, the most common organisms were staphylococci (51.8%) and Gram-negative organisms constituted 15.6% of all pathogens.”
7. Could you please confirm if there have been multiple revisions related to prosthetic joint infection caused by fungi or mycobacteria?
→ We added this sentence in the results section of revised manuscript.
“In 3 out of 5 cases in which mycobacteria were identified and in 7 out of 13 cases in which fungus was identified, multiple revision operations were performed.”
8. “received antibiotics before operation” – as a treatment or perioperative prophylaxis?
→ This refers to cases where antibiotics are used for therapeutic purposes, not prophylaxis. We have used term more clearly.
“In our work, about 46% of patients received antibiotics treatment before operation and 70% of patients yielded ≤ 4 tissue samples.”
Decision Letter 1
2 Jul 2024
PONE-D-24-06916R1The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?PLOS ONE
Dear Dr. Park,
Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.
Please submit your revised manuscript by Aug 16 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at gro.solp@enosolp. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.
Please include the following items when submitting your revised manuscript:
A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.
If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.
We look forward to receiving your revised manuscript.
Kind regards,
Abbas Farmany
Academic Editor
PLOS ONE
Journal Requirements:
Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.
Additional Editor Comments:
- Add a statistical analysis section in the M&M.
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Reviewers' comments:
Reviewer's Responses to Questions
Comments to the Author
1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.
Reviewer #2: All comments have been addressed
**********
2. Is the manuscript technically sound, and do the data support the conclusions?
The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.
Reviewer #2: Yes
**********
3. Has the statistical analysis been performed appropriately and rigorously?
Reviewer #2: Yes
**********
4. Have the authors made all data underlying the findings in their manuscript fully available?
The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.
Reviewer #2: Yes
**********
5. Is the manuscript presented in an intelligible fashion and written in standard English?
PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.
Reviewer #2: Yes
**********
6. Review Comments to the Author
Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)
Reviewer #2: Dear Authors,
The revisions you have made in response to the comments from both myself and the other reviewer have significantly enhanced the quality of the manuscript. The improvements are evident and have addressed the key concerns raised during the review process.
From my perspective, the manuscript has now reached a standard that warrants further consideration for acceptance. I believe it will make a valuable contribution to the field.
Thank you for your diligent efforts in refining your work.
**********
7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.
If you choose “no”, your identity will remain anonymous but your review may still be made public.
Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.
Reviewer #2: No
**********
[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]
While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at gro.solp@serugif. Please note that Supporting Information files do not need this step.
Author response to Decision Letter 1
2 Aug 2024
Title: The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?
Dear Editor-in-Chief
I would like to thank you for giving us the opportunity to revise our work. We have revised the manuscript in light of the valuable suggestions, and we believe it has been greatly improved. Attached you will find our revised manuscript, as well as our responses to the comments. This manuscript has not been published in any journal and is not under consideration for publication elsewhere. All authors including myself have seen and approved this manuscript.
Again, we thank you and the reviewers for a constructive and helpful review.
Here are the detailed descriptions
Sincerely yours,
Kyung-Hwa Park
Department of Infectious diseases,
Chonnam National University Medical School
42 Jebong-ro, Dong-gu, Gwangju, 61469, Korea
Responses to edditor’s additional comments:
#1: This is an important topic especially since we need a diverse voice in Ortho research. However, it needs further work before being ready for publication.
→ As recommended, we have added a statistical analysis section in the M&M.
#2: Separate the conclusion section.
→ As recommended, we have separated the conclusion section.
Decision Letter 2
6 Aug 2024
The microbiology of periprosthetic joint infections as revealed by sonicate cultures in Korea: Routine use of fungal and mycobacterial cultures is necessary?
PONE-D-24-06916R2
Dear Dr. Park,
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Abbas Farmany
Academic Editor
PLOS ONE
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Acceptance letter
8 Aug 2024
PONE-D-24-06916R2
PLOS ONE
Dear Dr. Park,
I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.
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Kind regards,
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on behalf of
Dr. Abbas Farmany
Academic Editor
PLOS ONE
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Funding
Funders who supported this work.
Chonnam National University (2)
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