Objectives: This systematic review and meta-analysis was conducted to assess the outcome of streptococcal hip and knee prosthetic joint infection (PJI) treated with Debridement, Antibiotics and... Show moreObjectives: This systematic review and meta-analysis was conducted to assess the outcome of streptococcal hip and knee prosthetic joint infection (PJI) treated with Debridement, Antibiotics and Implant Retention (DAIR) and to evaluate risk factors associated with failure. Methods: We conducted a systematic literature search on PubMed, Embase, Web of Science, and Cochrane library from inception until October 2021. Random effects meta-analyses (i.e. relative risk) were used to estimate the success rate at the study level and its association with possible risk factors for failure with a specific focus on the use of rifampicin.Results: 25 observational studies were included, incorporating 1367 patients with streptococcal PJIs treated with DAIR. An overall pooled success rate of 71% (95% confidence interval (95%CI) 64-77%) was found for streptococcal PJI treated with DAIR. Treatment success was 76% (95%CI 62% to 91%) for knee PJI and 58% (95%CI 52% to 65%) for hip PJI. Treatment success differed for patients receiving rifampicin (84%, 95% CI 78% to 90%) compared to patients not receiving rifampicin (74%, 95% CI 63% to 85%), but this effect was no longer present in subsequent meta-analyses. Conclusions: The meta-analysis showed no clear benefit for rifampicin administration after DAIR for streptococcal PJI. Better outcome was observed for knee PJI compared to hip PJI. Show less
A prosthetic joint infection (PJI) is a severe complication after arthroplasty. From the current thesis, three main conclusion can be drawn regarding diagnosis and treamtent of PJI. (a) Accurate... Show moreA prosthetic joint infection (PJI) is a severe complication after arthroplasty. From the current thesis, three main conclusion can be drawn regarding diagnosis and treamtent of PJI. (a) Accurate self-monitoring of postoperative wounds after joint implantation helped elucidate the course of wound leakage and its association with acute prosthetic joint infections. (b) The collection of clinical data on different antimicrobial treatment strategies provided insight into the effectiveness of different treatment options for patients with a prosthetic joint infection. In this thesis, we report that personalized antimicrobial treatment for prosthetic joint infections is possible without compromising the effectiveness of treatment. (c) this thesis describes the role and importance of new anti-persister drugs against biofilm-associated infections. We developed a biofilm model that closely resembles the clinic of a prosthetic joint infection. Based on the results described in this thesis, future research will be aimed at better understanding the pathogenesis of biofilms. This should ultimately lead to better treatment options for patients with a prosthetic joint infection. Show less
Introduction: A periprosthetic joint infection (PJI) is a major complication of arthroplasty. Treatment of PJI consists of surgical debridement with or without the exchange of the implant and long... Show moreIntroduction: A periprosthetic joint infection (PJI) is a major complication of arthroplasty. Treatment of PJI consists of surgical debridement with or without the exchange of the implant and long-term antimicrobial treatment. Rifampicin is regarded as one of the cornerstones of antimicrobial treatment for staphylococcal PJI, but the exact role of rifampicin for PJI in different clinical scenarios remains to be elucidated.Areas covered: In this perspective article, an overview is provided of in vitro, in vivo and clinical studies that were the basis of the current guidelines and recommendations for rifampicin use in daily practice for PJI. Controversial issues on indication, dosing, timing, duration, and antibiotic drug interactions will be addressed. Finally, the most urgent clinical questions on rifampicin use that need answering in the nearby future will be formulated.Expert Opinion: Many inquiries remain concerning the exact indications and clinical use of rifampicin in PJI. Randomized controlled trials are needed to answer these questions. Show less
Dun, S.C.J. van; Verheul, M.; Pijls, B.G.C.W.; Prehn, J. van; Scheper, H.; Galli, F.; ... ; Boer, M.G.J. de 2023
Introduction: One of the main causes of treatment failure in bacterial prosthetic joint infections (PJI) is biofilm formation. The topography of the biofilm may be associated with susceptibility to... Show moreIntroduction: One of the main causes of treatment failure in bacterial prosthetic joint infections (PJI) is biofilm formation. The topography of the biofilm may be associated with susceptibility to antimicrobial treatment. The aims of this study were to assess differences in topography of biofilms on different implant materials and the correlation thereof with susceptibility to antimicrobial treatment. Methods: Methicillin-resistant Staphylococcus aureus (MRSA) 7-day mature biofilms were generated on disks made from titanium alloys (Ti-6Al-7Nb and Ti-6Al-4V), synthetic polymer and orthopedic bone cement, commonly used in implant surgery. The surface topography of these implant materials and the biofilms cultured on them was assessed using atomic force microscopy. This provided detailed images, as well as average roughness (Ra) and peak-to-valley roughness (Rt) values in nanometers, of the biofilm and the material surfaces. Bacterial counts within biofilms were assessed microbiologically. Antimicrobial treatment of biofilms was performed by 24-h exposure to the combination of rifampicin and ciprofloxacin in concentrations of 1-, 5- and 10-times the minimal bactericidal concentration (MBC). Finally, treatment-induced differences in bacterial loads and their correlation with biofilm surface parameters were assessed. Results: The biofilm surfaces on titanium alloys Ti-6Al-7Nb (Ra = 186 nm) and Ti-6Al-4V (Ra = 270 nm) were less rough than those of biofilms on silicone (Ra = 636 nm). The highest roughness was observed for biofilms on orthopedic bone cement with an Ra of 1,551 nm. Interestingly, the roughness parameters of the titanium alloys themselves were lower than the value for silicone, whereas the surface of the bone cement was the roughest. Treatment with 1- and 5-times the MBC of antibiotics resulted in inter-material differences in colony forming units (CFU) counts, ultimately showing comparable reductions of 2.4-3.0 log CFU/mL at the highest tested concentration. No significant differences in bacterial loads within MRSA biofilms were observed between the various implant materials, upon exposure to increasing concentrations of antibiotics. Discussion: The surface parameters of MRSA biofilms were determined by those of the implant materials on which they were formed. The antibiotic susceptibility of MRSA biofilms on the various tested implant materials did not differ, indicating that the efficacy of antibiotics was not affected by the roughness of the biofilm. Show less
Scheper, H.; Mahdad, R.; Elzer, B.; Lowik, C.; Zijlstra, W.; Gosens, T.; ... ; Wound Care App Study Grp 2023
Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation.Prospective data about the duration... Show moreBackground: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation.Prospective data about the duration and amount of postoperative wounddrainage in patients with and without prosthetic joint infection (PJI) are currently absent.Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files.Results: Of the 1019 included patients, 16 patients (1.6 %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50 % to 3 %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95 % confidence interval (CI)26.08 to 408.57, OR 80.71, 95 % CI 9.12 to 714.52, respectively). Thepositive predictive value (PPV) for PJI was 83 % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were stronglyassociated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI. Show less
Scheper, H.; Mahdad, R.; Elzer, B.; Löwik, C.; Zijlstra, W.; Gosens, T.; ... ; Wound Care App Study Grp 2023
Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration... Show moreBackground: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration and amount of postoperative wound drainage in patients with and without prosthetic joint infection (PJI) are currently absent. Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files. Results: Of the 1019 included patients, 16 patients (1.6 %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50 % to 3 %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95 % confidence interval (CI) 26.08 to 408.57, OR 80.71, 95 % CI 9.12 to 714.52, respectively). The positive predictive value (PPV) for PJI was 83 % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were strongly associated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI. Show less
Scheper, H.; Wal, R.J.P. van der; Mahdad, R.; Keizer, S.; Delfos, N.M.; Lugt, J.C.T. van der; ... ; Boer, M.G.J. de 2022
Outcome of staphylococcal PJI after DAIR or 1-stage exchange was similar between patients treated with a long-term rifampicin combination therapy strategy and patients treated with only 5 days of... Show moreOutcome of staphylococcal PJI after DAIR or 1-stage exchange was similar between patients treated with a long-term rifampicin combination therapy strategy and patients treated with only 5 days of rifampicin combination therapy followed by clindamycin or flucloxacillin monotherapy.Background Treatment of staphylococcal prosthetic joint infection (PJI) usually consists of surgical debridement and prolonged rifampicin combination therapy. Tailored antimicrobial treatment alternatives are needed due to frequent side effects and drug-drug interactions with rifampicin combination therapy. We aimed to assess the effectiveness of several alternative antibiotic strategies in patients with staphylococcal PJI. Methods In this prospective, multicenter registry-based study, all consecutive patients with a staphylococcal PJI, treated with debridement, antibiotics and implant retention (DAIR) or 1-stage revision surgery between January 1, 2015 and November 3, 2020, were included. Patients were treated with a long-term rifampicin combination strategy (in 2 centers) or a short-term rifampicin combination strategy (in 3 centers). Antimicrobial treatment strategies in these centers were defined before the start of the registry. Patients were stratified in different groups, depending on the used antimicrobial strategy. Cox proportional hazards models were used to compare outcome between the groups. Results Two hundred patients were included and stratified in 1 long-term rifampicin group (traditional rifampicin combination therapy) or 1 of 3 short-term rifampicin groups (clindamycin or flucloxacillin or vancomycin monotherapy, including rifampicin for only 5 postoperative days). Adjusted hazard ratios (aHRs) for failure in patients treated with short-term rifampicin and either flucloxacillin or clindamycin were almost equal to patients treated with long-term rifampicin combination therapy (aHR = 1.21; 95% confidence interval, .34-4.40). Conclusions A short-term rifampicin strategy with either clindamycin or flucloxacillin and only 5 days of rifampicin was found to be as effective as traditional long-term rifampicin combination therapy. A randomized controlled trial is needed to further address efficacy and safety of alternative treatment strategies for staphylococcal PJI. Show less
Gerritsen, M.; Khawar, A.; Scheper, H.; Wal, R. van der; Schoones, J.; Boer, M. de; ... ; Pijls, B. 2021
AimsThe aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee... Show moreAimsThe aim of this meta-analysis is to assess the association between exchange of modular parts in debridement, antibiotics, and implant retention (DAIR) procedure and outcomes for hip and knee periprosthetic joint infection (PJI).MethodsWe conducted a systematic search on PubMed, Embase, Web of Science, and Cochrane library from inception until May 2021. Random effects meta-analyses and meta-regression was used to estimate, on a study level, the success rate of DAIR related to component exchange. Risk of bias was appraised using the (AQUILA) checklist.ResultsWe included 65 studies comprising 6,630 patients. The pooled overall success after DAIR for PJI was 67% (95% confidence interval (CI) 63% to 70%). This was 70% (95% CI 65% to 75%) for DAIR for hip PJI and 63% (95% CI 58% to 69%) for knee PJI. In studies before 2004 (n = 27), our meta-regression analysis showed a 3.5% increase in success rates for each 10% increase in component exchange in DAIR for hip PJI and a 3.1% increase for each 10% increase in component exchange for knee PJI. When restricted to studies after 2004 (n = 37), this association changed: for DAIR for hip PJI a decrease in successful outcome by 0.5% for each 10% increase in component exchange and for DAIR for knee PJI this was a 0.01% increase in successful outcome for each 10% increase in component exchange.ConclusionThis systematic review and meta-regression found no benefit of modular component exchange on reduction of PJI failure. This limited effect should be weighed against the risks for the patient and cost on a case-by-case basis. The association between exchange of modular components and outcome changed before and after 2004. This suggests the effect seen after 2004 may reflect a more rigorous, evidence-based, approach to the infected implant compared to the years before. Show less
The treatment of staphylococcal prosthetic joint infection (PJI) with debridement, antibiotics, and retention of the implant (DAIR) often results in failure. An important evidence gap concerns the... Show moreThe treatment of staphylococcal prosthetic joint infection (PJI) with debridement, antibiotics, and retention of the implant (DAIR) often results in failure. An important evidence gap concerns the treatment with rifampicin for PJI. A systematic review and meta-analysis were conducted to assess the outcome of staphylococcal hip and/or knee PJI after DAIR, focused on the role of rifampicin. Studies published until September 2, 2020 were included. Success rates were stratified for type of joint and type of micro-organism. Sixty-four studies were included. The pooled risk ratio for rifampicin effectiveness was 1.10 (95% confidence interval, 1.00-1.22). The pooled success rate was 69% for Staphylococcus aureus hip PJI, 54% for S aureus knee PJI, 83% for coagulase-negative staphylococci (CNS) hip PJI, and 73% for CNS knee PJI. Success rates for MRSA PJI (58%) were similar to MSSA PJI (60%). The metaanalysis indicates that rifampicin may only prevent a small fraction of all treatment failures. Show less
Background: Clinicians need to rapidly and reliably diagnose coronavirus disease 2019 (COVID-19) for proper risk stratification, isolation strategies, and treatment decisions.Purpose: To assess the... Show moreBackground: Clinicians need to rapidly and reliably diagnose coronavirus disease 2019 (COVID-19) for proper risk stratification, isolation strategies, and treatment decisions.Purpose: To assess the real-life performance of radiologist emergency department chest CT interpretation for diagnosing COVID-19 during the acute phase of the pandemic, using the COVID-19 Reporting and Data System (CO-RADS).Materials and Methods: This retrospective multicenter study included consecutive patients who presented to emergency departments in six medical centers between March and April 2020 with moderate to severe upper respiratory symptoms suspicious for COVID-19. As part of clinical practice, chest CT scans were obtained for primary work-up and scored using the five-point CO-RADS scheme for suspicion of COVID-19. CT was compared with severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (RT-PCR) assay and a clinical reference standard established by a multidisciplinary group of clinicians based on RT-PCR, COVID-19 contact history, oxygen therapy, timing of RT-PCR testing, and likely alternative diagnosis. Performance of CT was estimated using area under the receiver operating characteristic curve (AUC) analysis and diagnostic odds ratios against both reference standards. Subgroup analysis was performed on the basis of symptom duration grouped presentations of less than 48 hours, 48 hours through 7 days, and more than 7 days.Results: A total of 1070 patients (median age, 66 years; interquartile range, 54-75 years; 626 men) were included, of whom 536 (50%) had a positive RT-PCR result and 137 (13%) of whom were considered to have a possible or probable COVID-19 diagnosis based on the clinical reference standard. Chest CT yielded an AUC of 0.87 (95% CI: 0.84, 0.89) compared with RT-PCR and 0.87(95% CI: 0.85, 0.89) compared with the clinical reference standard. A CO-RADS score of 4 or greater yielded an odds ratio of 25.9 (95% CI: 18.7, 35.9) for a COVID-19 diagnosis with RT-PCR and an odds ratio of 30.6 (95% CI: 21.1, 44.4) with the clinical reference standard. For symptom duration of less than 48 hours, the AUC fell to 0.71 (95% CI: 0.62, 0.80; P =.001).Conclusion: Chest CT analysis using the coronavirus disease 2019 (COVID-19) Reporting and Data System enables rapid and reliable diagnosis of COVID-19, particularly when symptom duration is greater than 48 hours. (C) RSNA, 2020 Show less
Prosthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and... Show moreProsthetic joint infection (PJI) is a severe complication of arthroplasty. Due to biofilm and persister formation current treatment strategies often fail. Therefore, innovative anti-biofilm and anti-persister agents are urgently needed. Antimicrobial peptides with their broad antibacterial activities may be such candidates. An in vitro model simulating PJI comprising of rifampicin/ciprofloxacin-exposed, mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms on polystyrene plates, titanium/aluminium/niobium disks, and prosthetic joint liners were developed. Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan. Microcalorimetry was used to monitor the heat flow by the bacteria in these models. Daily exposure of mature biofilms to rifampicin/ciprofloxacin for 3 days resulted in a 4-log reduction of MRSA. Prolonged antibiotic exposure did not further reduce bacterial counts. Microcalorimetry confirmed the low metabolic activity of these persisters. SAAP-148 and pexiganan, but not LL-37, eliminated the persisters while ADEP4 reduced the number of persisters. SAAP-148 further eradicated persisters within antibiotics-exposed, mature biofilms on the various surfaces. To conclude, antibiotic-exposed, mature MRSA biofilms on various surfaces have been developed as in vitro models for PJI. SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections. Show less
Scheper, H.; Derogee, R.; Mandad, R.; Wal, R.J.P. van der; Nelissen, R.G.H.H.; Visser, L.G.; Boer, M.G.J. de 2019