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.

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.

h 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. CASE REPORTA 74-year-old lady from a regional town in the Eyre Peninsula of South Australia with a 4-day history of mental state deterioration, fever, and a loss of coordination was transferred to the Royal Adelaide Hospital. She was moderately immune suppressed by methotrexate and etanercept treatment for rheumatoid arthritis and had a history of diabetes. During the admission, her conscious state deteriorated rapidly, requiring mechanical ventilation and admission to the intensive care unit (ICU). Subsequently, she developed signs of brainstem involvement and exhibited a loss of corneal and gag reflexes. She was administered benzylpenicillin, ceftriaxone, and aciclovir for presumptive meningoencephalitis of bacterial or viral etiology. Cerebrospinal fluid (CSF) obtained by lumbar puncture demonstrated 280 ϫ10 6 polymorphonuclear leukocytes (PMN)/liter, 18 ϫ10 6 mononuclear lymphocytes/liter, elevated CSF protein of 1.59 g/liter, and CSF glucose of 3.3 mmol/ liter; aerobic and anaerobic bacterial culture results were negative, as were PCR results for Streptococcus pneumoniae, Neisseria meningitidis, herpes simplex virus, and varicella-zoster virus. CSF India ink stain and cryptococcal antigen lateral flow assay (Immy, Inc., Norman, OK, USA) results were negative. Magnetic resonance imaging (MRI) of the brain exhibited a left-predominant, asymmetrical meningeal enhancement in the frontoparietal cortex, without any detectable brainstem changes. Two days later, repeated lumbar punctures showed a marked elevation of PMN to 2,500 ϫ10 6 cells/liter and 34 ϫ10 6 mononuclear cells/liter, with no bacteria detected upon Gram staining. CSF stained with DiffQuick (Alere, Brisbane, Australia) showed 99% PMN with very few eosinophils. CSF protein was markedly elevated (5.46 g/liter), and CSF glucose was 1.3 mmol/liter. Microscopic examination of 100 l of unstained CSF was performed after centrifugation at 700 ϫ g for 10 min, but no amoebic trophozoites were detected. With a suspicion of parasitic infection, given the unexplained high PMN counts, the antimicrobial treatment strategy was changed to liposomal amphotericin B, sulfadiazine, pentamidine, and azithromycin to target protists such as amoebae and Toxoplasma gondii. CSF was subjected to PCR for Naegleria fowleri, Acanthamoeba sp., and Balamuthia mandrillaris, but all test results were negative. No anti-Strongyloides serum antibody (IgG) was detected in an enzyme-linked immunosorbent assay using somatic larval antigens from Strongyloides ratti (Bordier Affinity Pr...

In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. A total of 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, P = .03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, P = .03) and younger age (OR 0.98, 95% CI 0.97-0.99, P = .05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23, 95% CI 0.07-0.74, P = .01) and genotype 3 (OR 0.23, 95% CI 0.12-0.43, P ≤ .01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials; however, a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlight the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets.