Determination of vancomycin and meropenem in serum and synovial fluid of patients with prosthetic joint infections using UPLC-MS/MS.

Numerous studies have suggested that intra-articular administration of antibiotics following primary revision surgery may be one of the methods for treating prosthetic joint infection (PJI). Vancomycin and meropenem are the two most commonly used antibiotics for local application. Determining the concentrations of vancomycin and meropenem in the serum and synovial fluid of patients with PJI plays a significant role in further optimizing local medication schemes and effectively eradicating biofilm infections. This study aimed to establish a rapid, sensitive, and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the concentrations of vancomycin and meropenem in human serum and synovial fluid. Serum samples were processed using acetonitrile precipitation of proteins and dichloromethane extraction, while synovial fluid samples were diluted before analysis. Chromatographic separation was achieved in 6 min on a Waters Acquity UPLC BEH C18 column, with the mobile phase consisting of 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Quantification was carried out using a Waters XEVO TQD triple quadrupole mass spectrometer with an electrospray ionization (ESI) source in positive ion mode. The multiple reaction monitoring (MRM) mode was employed to detect the following quantifier ion transitions: 717.95-99.97 (norvancomycin), 725.90-100.04 (vancomycin), 384.16-67.99 (meropenem). The method validation conformed to the guidelines of the FDA and the Chinese Pharmacopoeia. The method demonstrated good linearity within the range of 0.5-50 µg/ml for serum and 0.5-100 µg/ml for synovial fluid. Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, matrix effect, and stability validation results all met the required standards. This method has been successfully applied in the pharmacokinetic/pharmacodynamic (PK/PD) studies of patients with PJI.

Triggered Release of Ampicillin from Metallic Implant Coatings for Combating Periprosthetic Infections.

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin ß-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the ß-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the ß-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.

Use of thioglycolate broth as a pre-analytic transport medium in the diagnosis of prosthetic joint infection.

OBJECTIVES: This study aimed to investigate whether adding tissue samples directly into thioglycolate (TG) broth yielded a greater number of anaerobic organisms than freshly sampled tissue in suspected hip and knee prosthetic joint infections (PJIs). PATIENTS AND METHODS: Between January 2017 and December 2020, a total of 90 patients (46 males, 44 females; median age: 71.7 years; range, 50.8 and 87.8 years) who underwent revision hip or knee arthroplasty were included. Intraoperative samples were taken, with five placed in TG broth and five in standard containers (PC) with subsequent aerobic and anaerobic culturing conducted. Demographic and baseline data of the patients were recorded. The primary outcome was positive bacterial growth from a PJI specimen inoculated directly into TG broth at the time of collection or standard PJI specimen processing. Secondary outcomes investigated were the presence of Cutibacterium acnes (C. acnes) and the curative success of revision procedure. RESULTS: A total of 900 samples (450 PC and 450 TG) were taken from 90 revision arthroplasty patients (47 knees and 43 hips). There was no statistically significant difference in the number of positive bacterial growth samples between TG broth and standard processing (p=0.742). This was consistent with subgroup analysis analyzing C. acnes (p=0.666). CONCLUSION: In hip and knee arthroplasty, there is no benefit in substituting or adding TG broth as a culture medium to better identify both general bacterial species and C. acnes infections specifically. However, the use of TG may be useful in confirming a true positive result for infection.

Outcomes in orthopedic device infections due to Streptococcus agalactiae: a retrospective cohort study.

BACKGROUND: Group B streptococci (Streptococcus agalactiae) (GBS) is a rare cause of prosthetic joint infection (PJI) occurring in patients with comorbidities and seems to be associated with a poor outcome. Depiction of GBS PJI is scarce in the literature. METHODS: A retrospective survey in 2 referral centers for bone joint infections was done Patients with a history of PJI associated with GBS between 2014 and 2019 were included. A descriptive analysis of treatment failure was done. Risk factors of treatment failure were assessed. RESULTS: We included 61 patients. Among them, 41 had monomicrobial (67%) infections. The median duration of follow-up was 2 years (interquartile range 2.35) Hypertension, obesity, and diabetes mellitus were the most reported comorbidities (49%, 50%, and 36% respectively). Death was observed in 6 individuals (10%) during the initial management. The rate of success was 63% (26/41). Removal of the material was not associated with remission (p = 0.5). We did not find a specific antibiotic regimen associated with a better outcome. CONCLUSION: The results show that S. agalactiae PJIs are associated with high rates of comorbidities and a high treatment failure rate with no optimal treatment so far.

The Effect of Slime Factor in the Treatment of Spinal Implant Infections.

AIM: To investigate the effect of the biofilm-forming ability of the bacteria on treatment in rats by using biofilm-forming and nonbiofilm- forming strains of Staphylococcus aureus (S. aureus). MATERIAL AND METHODS: Forty rats were divided into four equal groups as Group 1A, 1B, 2A, and 2B. All rats underwent single distance lumbar laminectomy, and titanium implants were introduced. Group 1 rats were inoculated with Slime factor (-) S. aureus, while Group 2 rats were inoculated with biofilm Slime factor (+) S. aureus. None of the rats were given antibiotics. One week later, the surgical field was reopened and microbiological samples were taken. The implants of rats in Groups 1A and 2A were left in place, while the implants of rats in Groups 1B and 2B were removed. RESULTS: There was no statistically significant difference between the groups inoculated with slime factor (+) S. aureus; although, Groups 1A and 2A showed statistically significant difference. Statistical analysis with respect to bacterial count also showed a statistically significant difference between Groups 1A and 2A. There was a statistically significant difference between Group 1B and 2B. CONCLUSION: The results obtained in the present study reveal that in case of implant-dependent infection, the first sample taken can be checked for slime factor, and if there is infection with slime factor-negative bacterium, treatment without removing the implant may be recommended. S. aureus was used in the study because it is the most common cause of implant-related infection at surgical sites. Further studies using different bacterial species are needed to reach a definitive conclusion.

Positive Culture of Atypical Mycobacterium Avium Following Revision Total Knee Arthroplasty.

CASE: We report a rare case of mycobacterial periprosthetic joint infection (PJI) after primary total knee arthroplasty 14 years earlier. Progressive knee pain over three years with a negative PJI infectious workup led to revision total knee arthroplasty. A surprising result was isolation of Mycobacterium avium from tissue cultures taken at time of revision surgery. After six months of antibiotic treatment, the patient is alive with well- functioning pain-free TKA at over one-year follow-up. CONCLUSION: Periprosthetic joint infection can present acutely or chronically years following total knee arthroplasty. Depending on the infecting organism, patients can present with sepsis, or a more indolent slower course that mimics aseptic loosening. In the absence of positive pre-operative labs and cultures, and based on the Musculoskeletal Infection Society (MSIS) criteria, aseptic loosening is a diagnosis of exclusion. An atypical infectious organism should be considered a possible cause and may require specialized cultures of operative specimens.

Infección de prótesis aórtica abdominal: tratamiento alternativo / Infected abdominal aortic prosthesis: an alternative therapy

Introducción: la infección de prótesis aórtica en la cirugía vascular convencional es un evento catastrófico, con una alta tasa de morbilidad y de mortalidad. El tratamiento tradicional ha sido la remoción de la prótesis y la reconstrucción con bypass extraanatómico. En algunos casos, se ha llevado a cabo el reemplazo con prótesis impregnadas en antibiótico; en otros, el reemplazo con vena femoral superficial y también la cirugía abierta con drenaje de las colecciones asociadas y antibioticoterapia de por vida. Caso clínico: se presenta el reporte de un caso de infección protésica tratada con drenajes de las colecciones y antibioticoterapia de larga duración, con un resultado favorable un año después de su complicación. Discusión: en algunos casos, dada la severidad del paciente, es posible intentar un tratamiento conservador de esta nefasta complicación.(AU)

Introduction: in traditional vascular surgery, aortic prosthesis infection is a catastrophic event with high morbidity andmortality rates. Traditional treatment is the removal of the valve followed by extra-anatomic bypass reconstruction. Insome cases, antibiotic-impregnated prosthesis replacement has been performed. In others, superficial femoral veinreplacement, and open surgery with drainage of the associated collections and lifelong antibiotic therapy.Case report: this is the case of a patient with aortic prosthesis infection undergoing draining collections and lifelongantibiotic therapy with a favorable outcome 1 year after the complication.Discussion: in some cases, given the severity of the patient, we can try to treat this dreaded complication conservativel.(AU)

Absorbable antibiotic beads for treatment of LVAD driveline infections.

BACKGOUND: Infections of the left ventricular assist device (LVAD) driveline are a dreaded complication that results in high mortality and morbidity. METHOD: We retrospectively reviewed five consecutive patients with severe continuous-flow LVAD (HVAD, Heartmate 2, and Heartmate 3) driveline infection. These infections, which developed on an average of 960.4 ± 843.9 days after LVAD placement, were refractory to systemic antibiotics and local wound care. All were treated with extensive surgical debridement, local installation of absorbable antibiotic-loaded calcium sulfate beads (vancomycin and tobramycin), primary wound closure, and 6 weeks of systemic antibiotics after surgery. RESULTS: Four patients had resolution of DLI, and one had a recurrent infection at another part of the driveline 7 months after the complete resolution of the previous site. This patient was successfully treated with debridement and bead placements. Three patients still have their LVADs, while two received orthotopic heart transplants. At the time of the transplant, there was no evidence of gross infection of the LVAD drivelines or pumps. At the average follow-up time of 425.8 ± 151 days, no patients have an active infection. CONCLUSION: Treatment of LVAD driveline infection with absorbable antibiotic beads with primary wound closure is a viable option and merits further investigation.

Biofilm Microenvironment Activated Antibiotic Adjuvant for Implant-Associated Infections by Systematic Iron Metabolism Interference.

Hematoma, a risk factor of implant-associated infections (IAIs), creates a Fe-rich environment following implantation, which proliferates the growth of pathogenic bacteria. Fe metabolism is a major vulnerability for pathogens and is crucial for several fundamental physiological processes. Herein, a deferiprone (DFP)-loaded layered double hydroxide (LDH)-based nanomedicine (DFP@Ga-LDH) that targets the Fe-rich environments of IAIs is reported. In response to acidic changes at the infection site, DFP@Ga-LDH systematically interferes with bacterial Fe metabolism via the substitution of Ga3+ and Fe scavenging by DFP. DFP@Ga-LDH effectively reverses the Fe/Ga ratio in Pseudomonas aeruginosa, causing comprehensive interference in various Fe-associated targets, including transcription and substance metabolism. In addition to its favorable antibacterial properties, DFP@Ga-LDH functions as a nano-adjuvant capable of delaying the emergence of antibiotic resistance. Accordingly, DFP@Ga-LDH is loaded with a siderophore antibiotic (cefiderocol, Cefi) to achieve the antibacterial nanodrug DFP@Ga-LDH-Cefi. Antimicrobial and biosafety efficacies of DFP@Ga-LDH-Cefi are validated using ex vivo human skin and mouse IAI models. The pivotal role of the hematoma-created Fe-rich environment of IAIs is highlighted, and a nanoplatform that efficiently interferes with bacterial Fe metabolism is developed. The findings of the study provide promising guidance for future research on the exploration of nano-adjuvants as antibacterial agents.

Outcomes After Pseudomonas Prosthetic Joint Infections.

BACKGROUND: Pseudomonas species are a less common but devastating pathogen family in prosthetic joint infections (PJIs). Despite advancements in management, Pseudomonas PJIs remain particularly difficult to treat because of limited antibiotic options and robust biofilm formation. This study aimed to evaluate Pseudomonas PJI outcomes at a single institution and review outcomes reported in the current literature. METHODS: All hip or knee PJIs at a single institution with positive Pseudomonas culture were evaluated. Forty-two patients (24 hips, 18 knees) meeting inclusion criteria were identified. The primary outcome of interest was infection clearance at 1 year after surgical treatment, defined as reassuring aspirate without ongoing antibiotic treatment. Monomicrobial and polymicrobial infections were analyzed separately. A focused literature review of infection clearance after Pseudomonas PJIs was performed. RESULTS: One-year infection clearance was 58% (n = 11/19) for monomicrobial PJIs and 35% (n = 8/23) for polymicrobial PJIs. Among monomicrobial infections, the treatment success was 63% for patients treated with DAIR and 55% for patients treated with two-stage exchange. Monotherapy with an oral or intravenous antipseudomonal agent (minimum 6 weeks) displayed the lowest 1-year clearance of 50% (n = 6/12). Resistance to antipseudomonal agents was present in 16% (n = 3/19), and two of eight patients with monomicrobial and polymicrobial PJIs developed resistance to antipseudomonal therapy in a subsequent Pseudomonas PJI. Polymicrobial infections (55%) were more common with a mortality rate of 44% (n = 10/23) at a median follow-up of 3.6 years. CONCLUSION: Pseudomonas infections often present as polymicrobial PJIs but are difficult to eradicate in either polymicrobial or monomicrobial setting. A review of the current literature on Pseudomonas PJI reveals favorable infection clearance rates (63 to 80%) after DAIR while infection clearance rates (33 to 83%) vary widely after two-stage revision.

Effect of Antibiotic Spacer Dosing on Treatment Success in Two-Stage Exchange for Periprosthetic Joint Infection.

INTRODUCTION: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success. METHODS: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure. RESULTS: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147). CONCLUSION: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure.

Burden of Candida-related vascular graft infection: a nested-case control study.

PURPOSE: We aimed to assess risk factors of candida-related Vascular Graft Infections (VGIs). METHODS: We did a case-control study (1:4) matched by age and year of infection, nested in a cohort of patient with a history of VGIs. Cases were defined by a positive culture for Candida spp. in biological samples and controls were defined by a positive culture for bacterial strains only in biological samples. Risk factors for Candida-related VGIs were investigated using multivariate logistic regression. Mortality were compared using survival analysis. RESULTS: 16 Candida-related VGIs were matched to 64 bacterial-related VGIs. The two groups were comparable regarding medical history and clinical presentation. Candida-related VGIs were associated with bacterial strains in 88% (14/16). Gas/fluid-containing collection on abdominal CT scan and the presence of an aortic endoprosthesis were risk factors for Candida spp.-related VGIs [RRa 10.43 [1.81-60.21] p = 0.009 RRa and 6.46 [1.17-35.73] p = 0.03, respectively]. Candida-related VGIs were associated with a higher mortality when compared to bacterial-related VGIs (p = 0.002). CONCLUSIONS: Candida-related VGIs are severe. Early markers of Candida spp. infection are needed to improve their outcome. The suspicion of aortic endoprosthesis infection may necessitate probabilistic treatment with antifungal agents.

Mycobacterium flavescens Infection - An Unusual Case of Prosthetic Joint Infection.

INTRODUCTION: The onset of prosthetic joint infections (PJIs) is characterized by early onset defined as within 90 days of the procedure, delayed onset defined as within 3 to 12 months, and late onset defined as over 12 months. In only a scant number of case reports, Mycobacterium flavescens associated infections are typically found in sputum cultures and associated with various forms of penetrating joint traumas, particularly post-surgical interventions. Due to its rarity in presentation among cases of PJIs, we have presented a case of PJI caused by Mycobacterium flavescens. CASE PRESENTATION: We have, herein, reported a case of a 70-year-old male presenting with stabbing left knee pain over the past several months along with accompanying erythema and swelling with the presence of purulent discharge. Outpatient cultures have shown the growth of Mycobacterium flavescent; subsequently, the patient underwent a 2-stage revision arthroplasty and was treated with a three-drug regimen and implant 5 months later. Although being an atypical cause of PJIs, we emphasize the importance of considering NTM as a differential for immunocompromised patients, especially those with prior surgical intervention. DISCUSSION: Mycobacterium spp. related PJIs manifest clinical features similar to other bacteriacausing PJIs, such as warm, indurated edema at the surgical site resulting in wound dehiscence and joint effusion. Diagnosis of Mycobacterium spp. related PJIs includes history and physical examination findings, serum inflammatory markers, synovial fluid analysis, and culture. Concurrently with surgical interventions, utilization of antimicrobial agents provides additional control in Mycobacterium- related PJI. Mycobacterium flavescens should be included among other NTMs as a possible cause of PJIs.

Cathodic voltage-controlled electrical stimulation and betadine decontaminate nosocomial pathogens from implant surfaces.

Periprosthetic joint infection (PJI) after total joint arthroplasty is a major concern requiring multiple surgeries and antibiotic interventions. Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli are the predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can prolong resistance, further complicating the use of current treatments. Previous research has shown that cathodic voltage-controlled electrical stimulation (CVCES) is an effective technique to prevent/treat implant-associated biofilm infections on titanium (Ti) surfaces. This study thus evaluated the efficacy of CVCES via the use of 10% betadine alone and in combination with CVCES to eradicate lab-grown biofilms on cemented and cementless cobalt-chromium (CoCr) and Ti surfaces. CVCES treatment alone for 24 hours demonstrated no detectable CFU for E. coli and P. aeruginosa biofilms on cementless CoCr implants. In the presence of cement, E. coli biofilms had 106 CFUs/implant remaining after CVCES treatment alone; however, P. aeruginosa biofilms on cemented implants were reduced to below detectable limits. The use of 10% betadine treatment for 3 minutes followed by 24-hour CVCES treatment brought CFU levels to below detectable limits in E. coli and P. aeruginosa. The same was true for S. aureus biofilms on cementless patellofemoral implants as well as femoral and tibial implants. These treatment methods were not sufficient for eradication of S. aureus biofilms on cemented implants. These results suggest that CVCES alone and CVCES with 10% betadine are effective approaches to treating biofilms formed by certain bacterial species potentially leading to the treatment of PJI.IMPORTANCEPeriprosthetic joint infections (PJIs) are problematic due to requiring multiple surgeries and antibiotic therapies that are responsible for increased patient morbidity and healthcare costs. These infections become resistant to antibiotic treatment due to the formation of biofilms on the orthopedic surfaces. Cathodic voltage-controlled electrical stimulation (CVCES) has previously been shown to be an effective technique to prevent and treat biofilm infections on different surfaces. This study shows that CVCES can increase the efficacy of 10% betadine irrigation used in debridement, antibiotics, and implant retention by 99.9% and clear infection to below detection limits. PJI treatments are at times limited, and CVCES could be a promising technology to improve patient outcomes.

Articulating Spacers in Total Hip Arthroplasty: Surgical Technique and Outcomes.

Although one-stage exchange arthroplasty is gaining popularity, two-stage exchange arthroplasty remains the gold standard for the treatment of periprosthetic joint infections. Use of an articulating spacer for this procedure offers an avenue for maintaining hip motion and controlled weight-bearing, allowing local antibiotic elution. However, there is no uniform consensus on the optimal surgical protocol for using articulating spacers. This review describes the surgical technique for undertaking a first-stage exchange arthroplasty using an articulating spacer and discusses the pertinent literature on key concepts relating to periprosthetic joint infections in total hip arthroplasty to guide effective surgical decision making in these patients.

Innovations in the Isolation and Treatment of Biofilms in Periprosthetic Joint Infection: A Comprehensive Review of Current and Emerging Therapies in Bone and Joint Infection Management.

Periprosthetic joint infections (PJIs) are a devastating complication of joint arthroplasty surgeries that are often complicated by biofilm formation. The development of biofilms makes PJI treatment challenging as they create a barrier against antibiotics and host immune responses. This review article provides an overview of the current understanding of biofilm formation, factors that contribute to their production, and the most common organisms involved in this process. This article focuses on the identification of biofilms, as well as current methodologies and emerging therapies in the management of biofilms in PJI.

The outcomes of acute periprosthetic joint infection following unicompartmental knee replacement managed with early debridement, Antibiotics, and implant retention.

BACKGROUND: Periprosthetic joint infection (PJI) following unicompartmental knee replacement (UKR) is an uncommon, yet serious, complication. There is a paucity of evidence regarding the effectiveness of Debridement-Antibiotics-and-Implant-Retention (DAIR) in this setting. The aim of this study is to investigate the effectiveness of DAIR for acute UKR PJI. METHOD: Between 2006 and 2019, 5195 UKR were performed at our institution. Over this period, sixteen patients underwent DAIR for early, acute PJI. All patients met MSIS PJI diagnostic criteria. The median age at DAIR was 67 years (range 40-73) and 12 patients were male (75.0%). The median time to DAIR was 24 days (range 6-60). Patients were followed up for a median of 6.5 years (range1.4-10.5) following DAIR. RESULTS: 0.3% (16/5195) of UKR in our institution had a DAIR within 3 months. 15 of 16 patients (93.8%) were culture positive, with the most common organism MSSA (n = 8, 50.0%). Patients were treated with an organism-specific intravenous antibiotic regime for a median of 6 weeks, followed by oral antibiotics for a median duration of 6 months. The Kaplan-Meier survivor estimate for revision for PJI was 57% (95%CI: 28-78%) at five years, and survivor estimate for all cause revision 52% (95%CI: 25-74%).The median Oxford Knee Score for patients with a viable implant at final follow-up was 45 points (range 39-46). CONCLUSION: Early, acute PJI after UKR is rare. DAIR had a moderate success rate, with infection-free survivorship of 57% at 5 years. Those successfully treated with DAIR had excellent functional outcome and implant survival.

Two-dimensional liquid chromatography measurement of meropenem concentration in synovial fluid of patients with periprosthetic joint infection.

Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery. One potential treatment approach for PJI could be the combination of one-stage revision and intra-articular infusion of antibiotics. Meropenem is one of the commonly used intra-articular antibiotics in our institution. Determining the concentration of meropenem in the joint cavity could be crucial for optimizing its local application, effectively eradicating biofilm infection, and improving PJI treatment outcomes. In this study, we developed a simple, precise, and accurate method of two-dimensional liquid chromatography (2D-LC) for determining the concentration of meropenem in human synovial fluid. The method was then validated based on the guidelines of the Food and Drug Administration and the Chinese Pharmacopoeia. Meropenem showed good linearity in the range of 0.31-25.01 µg/mL (r ≥ .999). Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, and stability validation results were all within the acceptance range. This method has been successfully applied to the determination of synovial fluid samples from PJI patients, providing a useful detection method for meropenem therapeutic drug monitoring (TDM) in PJI patients.

Left ventricular assist device-associated driveline infections as a specific form of complicated skin and soft tissue infection/acute bacterial skin and skin structure infection - issues and therapeutic options.

PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.

Host and microbial characteristics associated with recurrent prosthetic joint infections.

Approximately 20% of patients after resection arthroplasty and antibiotic spacer placement for prosthetic joint infection develop repeat infections, requiring an additional antibiotic spacer before definitive reimplantation. The host and bacterial characteristics associated with the development of recurrent infection is poorly understood. A case-control study was conducted for 106 patients with intention to treat by two-stage revision arthroplasty for prosthetic joint infection at a single institution between 2009 and 2020. Infection was defined according to the 2018 Musculoskeletal Infection Society criteria. Thirty-nine cases ("recurrent-periprosthetic joint infection [PJI]") received at least two antibiotic spacers before clinical resolution of their infection, and 67 controls ("single-PJI") received a single antibiotic cement spacer before infection-free prosthesis reimplantation. Patient demographics, McPherson host grade, and culture results including antibiotic susceptibilities were compared. Fifty-two (78%) single-PJI and 32 (82%) recurrent-PJI patients had positive intraoperative cultures at the time of their initial spacer procedure. The odds of polymicrobial infections were 11-fold higher among recurrent-PJI patients, and the odds of significant systemic compromise (McPherson host-grade C) were more than double. Recurrent-PJI patients were significantly more likely to harbor Staphylococcus aureus. We found no differences between cases and controls in pathogen resistance to the six most tested antibiotics. Among recurrent-PJI patients, erythromycin-resistant infections were more prevalent at the final than initial spacer, despite no erythromycin exposure. Our findings suggest that McPherson host grade, polymicrobial infection, and S. aureus infection are key indicators of secondary or persistent joint infection following resection arthroplasty and antibiotic spacer placement, while bacterial resistance does not predict infection-related arthroplasty failure.