Osteomyelitis-relevant antibiotics at clinical concentrations show limited effectivity against acute and chronic intracellular S. aureus infections in osteocytes.

Osteomyelitis caused by Staphylococcus aureus can involve the persistent infection of osteocytes. We sought to determine if current clinically utilized antibiotics were capable of clearing an intracellular osteocyte S. aureus infection. Rifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin, and tigecycline were assessed for their minimum inhibitory concentration (MIC) and minimum bactericidal concentrations against 12 S. aureus strains, at pH 5.0 and 7.2 to mimic lysosomal and cytoplasmic environments, respectively. Those antibiotics whose bone estimated achievable concentration was commonly above their respective MIC for the strains tested were further assayed in a human osteocyte infection model under acute and chronic conditions. Osteocyte-like cells were treated at 1×, 4×, and 10× the MIC for 1 and 7 days following infection (acute model), or at 15 and 21 days of infection (chronic model). The intracellular effectivity of each antibiotic was measured in terms of CFU reduction, small colony variant formation, and bacterial mRNA expression change. Only rifampicin, levofloxacin, and linezolid reduced intracellular CFU numbers significantly in the acute model. Consistent with the transition to a non-culturable state, few if any CFU could be recovered from the chronic model. However, no treatment in either model reduced the quantity of bacterial mRNA or prevented non-culturable bacteria from returning to a culturable state. These findings indicate that S. aureus adapts phenotypically during intracellular infection of osteocytes, adopting a reversible quiescent state that is protected against antibiotics, even at 10× their MIC. Thus, new therapeutic approaches are necessary to cure S. aureus intracellular infections in osteomyelitis.

Effectiveness of direct-acting antiviral therapy among Aboriginal and Torres Strait Islander peoples with HCV infection in Australia: A national real-world cohort (REACH-C).

Aboriginal and Torres Strait Islander peoples experience a disproportionate burden of hepatitis C virus (HCV) infection. This study assessed the effectiveness of direct-acting antiviral (DAA) therapy among Aboriginal peoples in the three years following universal access in Australia. REACH-C, a national multicentre prospective cohort study, evaluated HCV treatment outcomes from sequential DAA initiations across 33 health services between March 2016 and June 2019. DAA effectiveness was assessed by sustained virological response (SVR) in the total (full analysis set) and effectiveness (modified analysis set excluding those lost to follow-up) populations. Overall, 915 (10%) Aboriginal and 8095 (90%) non-Indigenous people commenced DAA therapy, of whom 30% and 16% reported current injecting drug use and 73% and 42% were treated in primary care, respectively. SVR in the total and effectiveness populations was 74% and 94% among Aboriginal people and 82% and 94% among non-Indigenous people, with loss to follow-up contributing to lower SVR in the total population analysis (22% Aboriginal, 13% non-Indigenous). Among Aboriginal people, returning for follow-up was positively associated with older age (aOR 1.20; 95% CI 1.04, 1.39) and SVR was negatively associated with cirrhosis (aOR 0.39; 95% CI 0.19, 0.80) and prior DAA treatment (aOR 0.14; 95% CI 0.04, 0.49). Factors reflecting higher vulnerability or inequity were not associated with returning for testing or SVR. DAA therapy was highly effective among Aboriginal peoples with HCV treated through primary and tertiary services. Tailored community-led interventions are necessary to optimize follow-up and engagement. Sustained DAA uptake and equitable access to care, treatment and prevention are required for HCV elimination.

Staged Revision Hip Arthroplasty With Femoral Impaction Bone Grafting for Prosthetic Joint Infections: Radiostereometric Analyses and Clinical Outcomes at Minimum 5-Year Follow-Up.

BACKGROUND: There are ongoing concerns regarding the use of bone graft following prosthetic joint infection and subsequent implant subsidence. The aim of this study was to determine whether the use of a cemented stem combined with femoral impaction bone grafting (FIBG) at second stage revision for infection results in stable femoral stem fixation, determined by accurate methods, and good clinical results. METHODS: A prospective cohort of 29 patients underwent staged revision total hip arthroplasty for infection using an interval prosthesis followed by FIBG at the final reconstruction. The mean follow-up was 89 months (range, 8 to 167 months). Femoral implant subsidence was measured with radiostereometric analysis. Clinical outcomes included the Harris Hip Score, Harris Pain score and Société Internationale de Chirurgie Orthopédique et de Traumatologie activity scores. RESULTS: At 2-years follow-up the median stem subsidence relative to femur was -1.36 mm (range, -0.31 to -4.98), while the cement subsidence relative to femur was -0.05 mm (range, 0.36 to -0.73). At 5-years follow-up, the median stem subsidence relative to femur was -1.89 mm (range, -0.27 to -6.35), while the cement subsidence relative to femur was -0.06 mm (range, 0.44 to -0.55). There were 25 patients who were confirmed infection-free after the second stage revision with FIBG. The median Harris Hip Score improved from 51 pre-operatively to 79 at 5 years (P = .0130), and Harris Pain score from 20 to 40 (P = .0038). CONCLUSIONS: Stable femoral component fixation can be achieved with FIBG when reconstructing the femur after revision for infection without compromising infection cure rates and patient-reported outcomes.

Outcomes for the first wave of hospitalised patients with COVID-19 in the South Australian context: a retrospective audit.

BACKGROUND: The first case of corona virus disease (COVID-19) was detected in South Australia on 1 February 2020. The Royal Adelaide Hospital (RAH) is the state's designated quarantine hospital. AIM: To determine the characteristics, outcomes and predictors of outcomes for hospitalised patients with coronavirus disease (COVID-19) within the RAH. METHODS: We performed a retrospective audit of 103 patients diagnosed with COVID-19 who were discharged from the RAH between 14 February and 21 May 2020. We collected demographic, clinical and laboratory data through an audit of electronic medical records. The main outcome measures were: (i) the need for oxygen supplementation; (ii) need for intensive care unit (ICU) care; and (iii) death in hospital. RESULTS: The median age of patients was 60 years (range 19-85). A total of 55 (53%) patients was male. All patients were independent at baseline; 37 (36%) patients suffered from hypertension. Cardiovascular disease, respiratory disease and diabetes were present in fewer than 19 (18%) patients. Obesity was present in 24 (23%) patients; 39 (38%) patients required supplemental oxygen, 18 (17%) required ICU care and 4 (4%) patients died. Older patients were significantly more at risk of oxygen requirement (median 68 vs 57.5 years, P < 0.01), ICU admission (median 66.5 vs 60 years, P = 0.04) and death (median 74.5 vs 60 years, P = 0.02). We did not find a statistically significant association between gender, body mass index and poor outcomes. Lactate dehydrogenase (LDH) was the only parameter at admission associated with oxygen requirement, ICU care and death. Peak LDH, aspartate aminotransferase, alanine aminotransferase, C-reactive protein and neutrophil lymphocyte ratio were significantly associated with oxygen requirement, ICU admission and death (P < 0.05 for all of the above laboratory markers). CONCLUSIONS: Although our sample size was small, we found that certain comorbidities and laboratory values were associated with poor outcomes. This occurred in a setting where care was not influenced by limited hospital and intensive care beds.

Outcomes of community-based hepatitis C treatment by general practitioners and nurses in Australia through remote specialist consultation.

BACKGROUND: A unique model of care was adopted in Australia following introduction of universal subsidised direct-acting antiviral (DAA) access in 2016 in order to encourage rapid scale-up of treatment. Community-based medical practitioners and integrated hepatitis nurses initiated DAA treatment with remote hepatitis specialist approval of the planned treatment without physical review. AIMS: To evaluate outcomes of community-based treatment of hepatitis C virus (HCV) through this remote consultation process in the first 12 months of this model of care. METHODS: A retrospective chart review of patients undergoing community-based HCV treatment from general practitioners and integrated hepatitis nurse consultants through the remote consultation model in three state jurisdictions in Australia from 1 March 2016 to 28 February 2017. RESULTS: Sustained virological response at 12 weeks (SVR12) was confirmed in 383 (65.1%) of 588 subjects intended for treatment with a median follow-up time of 12 months (interquartile range 9-14 months). The SVR12 test was not performed in 159 (27.0%) of 588 and 307 (52.2%) of 588 did not have liver biochemistry rechecked following treatment. Subjects who completed follow up exhibited high SVR12 rates (383/392; 97.7%). Nurse-led treatment was associated with higher confirmation of SVR12 (73.7% vs 62.4%; P = 0.01) and liver biochemistry testing post treatment (57.5% vs 45.0%; P = 0.01). CONCLUSIONS: Community-based management of HCV through remote specialist consultation may be an effective model of care. Failure to check SVR12, recheck liver biochemistry and appropriate surveillance in patients with cirrhosis may emerge as significant issues requiring further support, education and refinement of the model to maximise effectiveness of future elimination efforts.

Fatal Strongyloides hyperinfection syndrome in an immunocompetent adult with review of the literature.

Strongyloides hyperinfection syndrome is rarely described in immunocompetent individuals. We present a case of fatal Strongyloides hyperinfection syndrome, and a literature review identifying nine other cases occurring in immunocompetent individuals, highlighting the challenges of diagnosis and treatment in this setting. While overall mortality is lower compared to immunocompromised patients, fatal outcomes still occur. A high index of suspicion is required for early diagnosis and treatment.

Influence of antimicrobial susceptibility reporting on junior doctors' decision to prescribe antimicrobials inappropriately.

Objectives: Inappropriate antimicrobial use drives antimicrobial resistance and is a global public health problem. This study examined whether withholding antimicrobial susceptibilities in combination with interpretive comments on microbiological reports influenced the decision to inappropriately prescribe antibiotics in a controlled survey. Methods: Seventy junior doctors attending educational sessions were given one of two surveys describing four clinical case vignettes (scenarios) in which antimicrobial treatment was not indicated. They were asked to select their preferred treatment from multiple choices. In the scenarios labelled 'A', the laboratory report did not report antibiotic susceptibilities, but included comments from the microbiologist. In the scenarios labelled 'B', the laboratory report included full organism identification and susceptibility results without additional comments. Results: For scenarios 1, 2 and 3 there was a significantly higher probability ( P < 0.01) that the doctor selected an answer involving antibiotic treatment if he/she received the 'B' version of the scenario where reports included antimicrobial susceptibilities, but no interpretive comments. This was significant in both interns and more senior doctors. In scenario 4, of which there were two versions, there was no difference seen in the answers between the groups given scenario A or B. Conclusions: The results of this survey suggest that withholding antimicrobial susceptibility results in combination with interpretive comments on microbiology reports significantly influences the decision of junior doctors to prescribe antibiotics in low-acuity outpatient setting scenarios (represented in scenarios 1-3), but not in inpatient scenarios (represented in scenario 4).

First human case of fatal Halicephalobus gingivalis meningoencephalitis in Australia.

Halicephalobus gingivalis (previously Micronema deletrix) is a free-living nematode known to cause opportunistic infections, mainly in horses. Human infections are very rare, but all cases described to date involved fatal meningoencephalitis. Here we report the first case of H. gingivalis infection in an Australian human patient, confirmed by nematode morphology and sequencing of ribosomal DNA. The implications of this case are discussed, particularly, the need to evaluate real-time PCR as a diagnostic tool.

Estimation of two-year hospital costs of hip and knee periprosthetic joint infection treatments using activity-based costing.

Aims: Our aim was to estimate the total costs of all hospitalizations for treating periprosthetic joint infection (PJI) by main management strategy within 24 months post-diagnosis using activity-based costing. Additionally, we investigated the influence of individual PJI treatment pathways on hospital costs within the first 24 months. Methods: Using admission and procedure data from a prospective observational cohort in Australia and New Zealand, Australian Refined Diagnosis Related Groups were assigned to each admitted patient episode of care for activity-based costing estimates of 273 hip PJI patients and 377 knee PJI patients. Costs were aggregated at 24 months post-diagnosis, and are presented in Australian dollars. Results: The mean cost per hip and knee PJI patient was $64,585 (SD $53,550). Single-stage revision mean costs were $67,029 (SD $47,116) and $80,063 (SD $42,438) for hip and knee, respectively. Two-stage revision costs were $113,226 (SD $66,724) and $122,425 (SD $60,874) for hip and knee, respectively. Debridement, antibiotics, and implant retention in hips and knees mean costs were $53,537 (SD$ 39,342) and $48,463 (SD $33,179), respectively. Suppressive antibiotic therapy without surgical management mean costs were $20,296 (SD $8,875) for hip patients and $16,481 (SD $6,712) for knee patients. Hip patients had 16 different treatment pathways and knee patients had 18 treatment pathways. Additional treatment, episodes of care, and length of stay contributed to substantially increased costs up to a maximum of $369,948. Conclusion: Treating PJI incurs a substantial cost burden, which is substantially influenced by management strategy. With an annual PJI incidence of 3,900, the cost burden would be in excess of $250 million to the Australian healthcare system. Treatment pathways with additional surgery, more episodes of care, and a longer length of stay substantially increase the associated hospital costs. Prospectively monitoring individual patient treatment pathways beyond initial management is important when quantifying PJI treatment cost. Our study highlights the importance of optimizing initial surgical treatment, and informs treating hospitals of the resources required to provide care for PJI patients.

Exploring the Health-Related Quality of Life and the Lived Experience of Adolescents Following Invasive Meningococcal Disease.

BACKGROUND: Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are limited. This study aimed to investigate the in-depth experiences and impacts of IMD on AYAs. METHODS: Participants were recruited from two Australian states, Victoria and South Australia. We conducted qualitative, semi-structured interviews with 30 patients diagnosed with IMD between 2016 and 2021. The interview transcripts were analyzed thematically. RESULTS: Of the participants, 53% were aged 15-19 years old, and 47% were aged 20-24. The majority (70%) were female. Seven themes relating to the participants' experience of IMD were identified: (1) underestimation of the initial symptoms and then rapid escalation of symptoms; (2) reliance on social support for emergency care access; (3) the symptoms prompting seeking medical care varied, with some key symptoms missed; (4) challenges in early medical diagnosis; (5) traumatic and life-changing experience; (6) a lingering impact on HRQoL; and (7) gaps in the continuity of care post-discharge. CONCLUSION: The themes raised by AYA IMD survivors identify multiple areas that can be addressed during their acute illness and recovery. Increasing awareness of meningococcal symptoms for AYAs may help reduce the time between the first symptoms and the first antibiotic dose, although this remains a challenging area for improvement. After the acute illness, conducting HRQoL assessments and providing multidisciplinary support will assist those who require more intensive and ongoing assistance during their recovery.

Cryptococcal endophthalmitis complicated by immune reconstitution inflammatory syndrome in a renal transplant recipient: A case report and review of the literature.

A 59 year old male renal transplant recipient developed endogenous cryptococcal endophthalmitis which was complicated by immune reconstitution inflammatory syndrome (IRIS). Herein we report a novel diagnostic test using lateral flow assay, the management of cryptococcal endophthalmitis and the novel complication of intraocular IRIS in a solid organ transplant recipient.

Long Cephalomedullary Nails Can Be a Cheap and Effective Interval Revision Prosthesis in Infected Hip Replacements That Require Proximal Femoral Replacement: A Small Case Series.

Hip prosthetic joint infection management is complex and expensive, especially in severe bone loss. Reducing the price of interval prosthesis when performing staged revision could minimize costs without compromising outcomes. We present 2 similar techniques developed independently that use an antibiotic-coated cephalomedullary nail with a total hip arthroplasty bearing (head and cemented acetabular component) attached to it as an interval proximal femoral replacement prosthesis. Using this technique, the femoral implant cost was reduced up to 10-fold. All patients have recovered well with resolution of infection and functional recovery similar to patients undergoing proximal femoral replacement. In one case, the lag screw (femoral neck) fractured at 5 months prompting the second-stage revision. This complication should be considered when deciding the timing of second-stage revisions in these cases.

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis.

Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat; however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rifampicin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.

Short- versus standard-course intravenous antibiotics for peri-prosthetic joint infections managed with debridement and implant retention: a randomised pilot trial using a desirability of outcome ranking (DOOR) endpoint.

BACKGROUND: Peri-prosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Determining the optimal duration of intravenous (IV) antibiotics for PJI managed with debridement and implant retention (DAIR) is a research priority. METHODS: Patients undergoing DAIR for early and late-acute PJI of the hip or knee were randomised to receive 2 (short-course) or 6 (standard-course) weeks of IV antibiotics, with both groups completing 12 weeks of antibiotics in total. The primary endpoint of this pilot, open-label, randomised trial was a 7-point ordinal desirability of outcome ranking (DOOR) score, which accounted for mortality, clinical cure and treatment adverse events at 12 months. Duration of IV treatment was used as a tiebreaker, with shorter courses ranked higher. Outcome adjudication was performed by expert clinicians blinded to the allocated intervention (Australia and New Zealand Clinical Trials Registry ACTRN12617000127303). RESULTS: 60 patients were recruited; 31 and 29 were allocated to short- and standard-course treatment, respectively. All had an evaluable outcome at 12 months and were analysed by intention-to-treat. Clinical cure was demonstrated in 44 (73%) overall; 22 (71%) in the short-course group and 22 (76%) in the standard-care group (P=0.77). Using the DOOR approach, the probability that short- was better than standard-course treatment was 59.7% (95% confidence interval 45.1-74.3). CONCLUSIONS: In selected patients with early and late-acute PJI managed with DAIR, shorter courses of IV antibiotics may be appropriate. Due to small sample size, these data accord with, but do not confirm, results from other international trials of early transition to oral antibiotics.

Predictors of Treatment Success After Periprosthetic Joint Infection: 24-Month Follow up From a Multicenter Prospective Observational Cohort Study of 653 Patients.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating condition and there is a lack of evidence to guide its management. We hypothesized that treatment success is independently associated with modifiable variables in surgical and antibiotic management. METHODS: The is a prospective, observational study at 27 hospitals across Australia and New Zealand. Newly diagnosed large joint PJIs were eligible. Data were collected at baseline and at 3, 12, and 24 months. The main outcome measures at 24 months were clinical cure (defined as all of the following: alive, absence of clinical or microbiological evidence of infection, and not requiring ongoing antibiotic therapy) and treatment success (clinical cure plus index prosthesis still in place). RESULTS: Twenty-four-month outcome data were available for 653 patients. Overall, 449 patients (69%) experienced clinical cure and 350 (54%) had treatment success. The most common treatment strategy was debridement and implant retention (DAIR), with success rates highest in early postimplant infections (119 of 160, 74%) and lower in late acute (132 of 267, 49%) and chronic (63 of 142, 44%) infections. Selected comorbidities, knee joint, and Staphylococcus aureus infections were independently associated with treatment failure, but antibiotic choice and duration (including rifampicin use) and extent of debridement were not. CONCLUSIONS: Treatment success in PJI is associated with (1) selecting the appropriate treatment strategy and (2) nonmodifiable patient and infection factors. Interdisciplinary decision making that matches an individual patient to an appropriate management strategy is a critical step for PJI management. Randomized controlled trials are needed to determine the role of rifampicin in patients managed with DAIR and the optimal surgical strategy for late-acute PJI.

Long-Term Outcomes of Staged Revision Surgery for Chronic Periprosthetic Joint Infection of Total Hip Arthroplasty.

Periprosthetic joint infection (PJI) is a serious complication of total hip arthroplasty. Staged revision surgery is considered effective in eradicating PJI. We aimed to determine the rate of infection resolution after each stage of staged revision surgery (first stage, repeat first stage, second stage, excision arthroplasty, and reimplantation) and to assess functional outcomes and the mortality rate at ten years in a consecutive series of 30 chronic PJI of total hip arthroplasties. Infection resolution was defined as no clinical nor laboratory evidence of infection at 24 months after the last surgery and after a minimum of 12 months following cessation of antimicrobial treatment. Four patients died within 24 months of their final surgery. Nineteen patients, 73% (worst-case analysis (wca) 63%), were infection free after 1 surgery; 22 patients, 85% (wca 73%), were infection free after 2 surgeries; and 26 patients, 100% (wca 87%), were infection free after three and four surgeries. The median Harris Hip Score was 41 prior to first revision surgery and improved to 74 at twelve months and 76 at ten years after the final surgery. Thirteen patients died at a mean of 64 months from first revision, giving a mortality rate of 43% at ten years, which is approximately 25% higher than that of an age-matched general population. The results show that with repeated aggressive surgical treatment, most PJIs of the hip are curable. Ten years after successful treatment of PJI, functional outcomes and pain are improved and maintained compared to before initial surgery, but this must be balanced against the high 10-year mortality. Level of evidence: cohort studies.

Cost effectiveness of treatment models of care for hepatitis C: the South Australian state-wide experience.

AIM: The objective was to study the long-term (lifetime) cost effectiveness of four different hepatitis C virus (HCV) treatment models of care (MOC) with directly acting antiviral drugs. METHODS: A cohort Markov model-based probabilistic cost-effectiveness analysis (CEA) was undertaken extrapolating to up to 30 years from cost and outcome data collected from a primary study involving a real-life Australian cohort. In this study, noncirrhotic patients treated for HCV from 1 March 2016 to 28 February 2017 at four major public hospitals and liaising sites in South Australia were studied retrospectively. The MOC were classified depending on the person providing patient workup, treatment and monitoring into MOC1 (specialist), MOC2 (mixed specialist and hepatitis nurse), MOC3 (hepatitis nurse) and MOC4 (general practitioner, GP). Incremental costs were estimated from the Medicare perspective. Incremental outcomes were estimated based on the quality-adjusted life years (QALY) gained by achieving a sustained virological response. A cost-effectiveness threshold of Australian dollar 50 000 per QALY gained, the implicit criterion used for assessing the cost-effectiveness of new pharmaceuticals and medical services in Australia was assumed. Net monetary benefit (NMB) estimates based on this threshold were calculated. RESULTS: A total of 1373 patients, 64% males, mean age 50 (SD ±11) years, were studied. In the CEA, MOC4 and MOC2 clearly dominated MOC1 over 30 years with lower costs and higher QALYs. Similarly, NMB was the highest in MOC4, followed by MOC2. CONCLUSION: Decentralized care using GP and mixed consultant nurse models were cost-effective ways of promoting HCV treatment uptake in the setting of unrestricted access to new antivirals.

Clinical Characteristics, Etiology, and Initial Management Strategy of Newly Diagnosed Periprosthetic Joint Infection: A Multicenter, Prospective Observational Cohort Study of 783 Patients.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Most observational studies of PJI are retrospective or single-center, and reported management approaches and outcomes vary widely. We hypothesized that there would be substantial heterogeneity in PJI management and that most PJIs would present as late acute infections occurring as a consequence of bloodstream infections. METHODS: The Prosthetic joint Infection in Australia and New Zealand, Observational (PIANO) study is a prospective study at 27 hospitals. From July 2014 through December 2017, we enrolled all adults with a newly diagnosed PJI of a large joint. We collected data on demographics, microbiology, and surgical and antibiotic management over the first 3 months postpresentation. RESULTS: We enrolled 783 patients (427 knee, 323 hip, 25 shoulder, 6 elbow, and 2 ankle). The mode of presentation was late acute (>30 days postimplantation and <7 days of symptoms; 351, 45%), followed by early (≤30 days postimplantation; 196, 25%) and chronic (>30 days postimplantation with ≥30 days of symptoms; 148, 19%). Debridement, antibiotics, irrigation, and implant retention constituted the commonest initial management approach (565, 72%), but debridement was moderate or less in 142 (25%) and the polyethylene liner was not exchanged in 104 (23%). CONCLUSIONS: In contrast to most studies, late acute infection was the most common mode of presentation, likely reflecting hematogenous seeding. Management was heterogeneous, reflecting the poor evidence base and the need for randomized controlled trials.