Alpha-defensin as a diagnostic tool in revision total knee arthroplasties with unexpected positive intraoperative cultures and unexpected culture negative intraoperative cultures.

PURPOSE: Unexpected-positive-intraoperative-cultures (UPIC) are common in presumed aseptic revision-total-knee-arthroplasties (rTKA). However, the clinical significance is not entirely clear. In contrast, in some presumably septic rTKA, identification of an underlying pathogen was not possible, so-called unexpected-negative-intraoperative-cultures (UNIC). The purpose of this study was to evaluate the potential use of synovial alpha-defensin (AD) levels in these patients. METHODS: Synovial AD levels from 143 rTKAs were evaluated retrospectively from our prospectively maintained institutional periprostetic joint infection (PJI) biobank and database. The 2018-International Consensus Meeting (ICM) criteria was used to define the study groups. Samples from UPICs with a minimum of one positive intraoperative culture (ICM 2- ≥ 6) (n = 20) and UNIC's (ICM ≥ 6) (n = 14) were compared to 34 septic culture-positive samples (ICM ≥ 6) and 75 aseptic culture-negative (ICM 0-1). Moreover, AD-lateral-flow-assay (ADLF) and an enzyme-linked-immunosorbent-assay (ELISA) in detecting the presence of AD in native and centrifuged synovial fluid specimens was performed. Concentration of AD determined by ELISA and ADLF methods, as well as microbiological, and histopathological results, serum and synovial parameters along with demographic factors were analysed. RESULTS: AD was positive in 31/34 (91.2%) samples from the septic culture-positive group and in 14/14 (100%) samples in the UNIC group. All UPIC samples showed a negative AD result. Positive AD samples were highly associated with culture positive and histopathological results (p < 0.001). No high-virulent microorganisms (0/20) were present in the UPIC group, compared to infected-group (19/34; 55.9%). High virulent microorganisms showed a positive AD result in 89.5% (17/19) of the cases. Methicillin resistant Staphylococcus epidermis (MRSE) infections had significantly higher AD levels than with methicillin susceptible S. epidermdis (MSSE) (p = 0.003). ELISA and ADLF tests were positive with centrifuged (8/8) and native (8/8) synovial fluid. CONCLUSION: AD showed a solid diagnostic performance in infected and non-infected revisions, and it provided an additional value in the diagnosis of UPIC and UNIC associated to rTKAs. Pathogen virulence as well as antibiotic resistance pattern may have an effect on AD levels. Centrifugation of synovial fluid had no influence on ADLF results.

Dalbavancin in Gram-positive periprosthetic joint infections.

OBJECTIVES: The unique properties of dalbavancin (DAL) emphasize the need to explore its clinical benefits to treat periprosthetic joint infections (PJIs). The present study aimed to compare the treatment outcome of dalbavancin with Standard of Care (SoC) in hip and knee PJIs. METHODS: Eighty-nine patients were selected for each group of this study based on our prospectively maintained PJI database. A 1:1 propensity score-matching was performed between patients who received at least two doses of dalbavancin and those who received SoC. Patients were matched based on demographics, joint, patient risk factors, Musculoskeletal Infection Society (MSIS) criteria, surgical management and type of infection. Treatment outcome was evaluated considering re-infection and re-revision rates, safety and tolerability of dalbavancin after a minimum of 1 year follow-up. RESULTS: Infection eradication was achieved in 69 (77.5%) and 66 (74.2%) patients of the DAL and SoC groups, respectively. Thirteen (14.6%) patients in the DAL group and 12 (13.5%) patients in the SoC group had an infection-related re-revision. The most prevalent microorganisms among the two groups were Staphylococcus epidermidis (32.3%), Staphylococcus aureus (13.8%) and Cutibacterium spp. (11.3%). There were significantly less Gram-positive bacteria (P = 0.03) detected in patients who received dalbavancin (17.4%) treatment compared with those treated with SoC (48.0%) in culture-positive re-revisions. CONCLUSIONS: Dalbavancin treatment for Gram-positive PJIs resulted in a similar outcome to SoC, with excellent safety and low rate of adverse effects. Dalbavancin seems to be a promising antimicrobial against PJIs by reducing the risk of Gram-positive re-infections and allowing a less frequent dosage with potential outpatient IV treatment.

Prevalence, risk factors, microbiological results and clinical outcome in unexpected positive intraoperative cultures in unclear and presumed aseptic hip and knee revision arthroplasties - A ten-year retrospective analysis with a minimum follow up of 2 years.

Background: The aim of this study was to assess the prevalence, microbiological spectrum, risk factors, and clinical outcomes of unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic and unclear revision-total-hip-/knee-arthroplasties (rTHA and rTKA) compared to culture-negative (CN) revisions. Methods: This study reviewed all International-consensus-meeting-2018 (ICM 2018) negative or inconclusive rTHA (n = 751) and rTKA (n = 679) performed at our institution from 2011 to 2020 with a minimum follow-up of two years. A Kaplan-Meier-analysis was performed to determine the septic and aseptic-free implant survival in cases with UPIC's and matched culture-negative cases. Patient demographics, risk factors, microbiological spectrum and clinical outcomes were evaluated. Results: There were significantly more UPIC cases in rTHA 196/751 (26.1 %) compared to rTKA 113/679 (16.6 %); (p < 0.001). UPICs in rTKA and rTHA have a lower septic and aseptic implant-free-survival compared to CN revisions. Patients with a history of nickel allergy have a higher risk of an UPIC in rTHA and rTKA (p < 0.001). Septic re-revisions after UPIC had a significantly (H: p = 0.004; K: p = 0.030) shorter time period to the primary/previous surgery (H: 84 (IQR:41-797); K: 115 (IQR:55-446)) compared to patients with aseptic re-revisions after UPIC (H:1248 (IQR:178-3534); K: 827 (IQR:361-1183)). Conclusion: UPICs have a higher rate of septic and aseptic failure than CN outcomes. UPICs are twice as common in rTHA compared to rTKA. Preoperative PJI workup reduces the UPIC rate. Nickel allergy is a risk factor for UPIC. Early revisions with UPICs after primary THA or TKA have a higher risk of septic failure. The translational potential of this article: This article provides new information on revision rates for UPIC and potential risk factors for UPIC and its treatment failure.

The role of BioFire Joint Infection Panel in diagnosing periprosthetic hip and knee joint infections in patients with unclear conventional microbiological results.

Aims: This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool. Methods: Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures. Results: The JI panel detected microorganisms in 7/48 (14.5%) and 15/67 (22.4%) cases related to UNCs and SPCs, respectively, but not in cases of UPCs. The correlation between JI panel detection and infection classification criteria for early/late acute and chronic PJI was 46.6%, 73%, and 40%, respectively. Overall, the JI panel identified 12.6% additional microorganisms and three new species. The JI panel pathogen identification showed a sensitivity and specificity of 41.4% (95% confidence interval (CI) 33.7 to 49.5) and 91.1% (95% CI 84.7 to 94.9), respectively. In total, 19/195 (9.7%) could have been managed differently and more accurately upon JI panel evaluation. Conclusion: Despite its microbial limitation, JI panel demonstrated clinical usefulness by complementing the traditional methods based on multiple cultures, particularly in PJI with unclear microbiological results.

Changes of the microbiological spectrum and antibiotic resistance pattern in postoperative spinal implant infections with multiple culture-positive revision surgeries.

BACKGROUND CONTEXT: In severe cases of postoperative spinal implant infections (PSII) multiple revision surgeries may be needed. Little is known if changes in the microbiological spectrum and antibiotic resistance pattern occur between revision surgeries. PURPOSE: Analysis of the microbiological spectrum and antibiotic resistance pattern in patients with multiple revision surgeries for the treatment of PSII STUDY DESIGN: Retrospective database analysis. PATIENT SAMPLE: Between 01/2011 and 12/2018, 103 patients underwent 248 revision surgeries for the treatment of PSII. Twenty patients (19.4%) who underwent multiple revision surgeries for PSII were included in this study. OUTCOME MEASURES: Microbiological spectrum, antibiotic resistance pattern. METHODS: A retrospective analysis of a prospectively maintained single center spine infection database was performed with a minimum follow-up of 3 years. Overall, 20 patients (six male/14 female) underwent 82 revisions for PSII (median 3; range 2-12). There were 55 of 82 (67.1%) procedures with a positive microbiological result. Microbiological analysis was performed on tissue and implant sonication fluid. Changes in microbial spectrum and antibiotic resistance pattern between surgeries were evaluated using Chi-Square and Fisher's exact test. RESULTS: In total, 74 microorganisms (83.3% gram-positive; 10.8% gram-negative) were identified. The most common microorganisms were Staphylococcus epidermidis (18.9%) and Cutibacterium acnes (18.9%). All S. epidermidis identified were methicillin-resistant (MRSE). Overall, there were 15 of 55 (27.3%) polymicrobial infections. The microbiological spectrum changed in 57.1% (20/35) between the revision stages over the entire PSII period. In 42.9% (15/35) the microorganism persisted between the revision surgeries stages. Overall, changes of the antibiotic resistance pattern were seen in 17.4% (8/46) of the detected microorganisms, comparing index revision and all subsequent re-revisions. Moreover, higher resistance rates were found for moxifloxacin and for ciprofloxacin at first re-revision surgery compared with index PSII revision. Resistances against vancomycin increased from 4.5% (1/23) at index PSII revision to 7.7% (2/26) at first re-revision surgery. CONCLUSIONS: Changes of the microbiological spectrum and the resistance pattern can occur in patients with severe PSII who require multiple revision surgeries. It is important to consider these findings in the antimicrobial treatment of PSII. The microbiological analysis of intraoperative tissue samples should be performed at every revision procedure for PSII.

ε2-Phages Are Naturally Bred and Have a Vastly Improved Host Range in Staphylococcus aureus over Wild Type Phages.

Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε2) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε2-phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε2-phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 1011). In summary, ε2-phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections.