The osteomyelitis literature, scant as it is at times, still dwarfs the literature on native joint septic arthritis (hereafter, NJSA) in scope and quality. While prosthetic joint infection is well-studied, the recommendations for antimicrobial therapy for NJSA you’ll find in UpToDate, Harrison’s and the like are informed by a few small retrospective studies and many decades of medical tradition. This isn’t to say that the current treatment approach is wrong, just that it’s closer to a belief system than evidence-based medicine.
There are no randomized controlled trials of specifically examining the treatment of NJSA - or at least there weren’t until this month, when Gjika and colleagues published their manuscript in Annals of Rheumatic Diseases. Since that’s not a journal regularly covered on this website, let’s discuss it now.
The investigators conducted an open-label RTC at a single Swiss hospital that randomized adults with NJSA to receive either 14 or 28 days of antimicrobial therapy. The primary outcome was remission of infection, defined as the absence of any clinical, laboratory, or radiographic findings of infection 2 months after completing treatment. For this study, NJSA was defined as the combination of clinical signs of septic arthritis plus a positive microbiologic test (i.e. joint fluid culture or PCR). The authors enrolled adults with NJSA who had undergo a source control procedure (e.g. open or arthroscopic washout), and excluded those with unusual pathogens (e.g. fungi, mycobacteria, gonococcus, brucella) or concomitant infections that would require longer durations of therapy (e.g. endocarditis).
A total 154 patients were randomized (n=77 in each arm), the majority of which represented NJSA of the hand and several of which were due to bites by cats, dogs, people, etcetera. The median age was about 50, ~40% were men, and three-quarters made it to surgery before being administered antibiotics. S. aureus (all MSSA) was the most common pathogen, followed by streptococci and gram-negatives. Only 3/154 patients were wholly treated with IV antibiotics; IV to PO switch was the most common strategy (n=122), followed by all oral therapy (n=32). Among the oral agents selected, amoxicillin-clavulanate was the most common (n=71), followed by quinolones (n=26), and clindamycin (n=19).
Overall rates of cure ranged from 97% to 99% and did not vary by treatment arm. Length of stay was shorter in the 2-week arm (4 vs 6 days; p=0.01). Rates of postinfectious sequelae (e.g. pain, stiffness) and antibiotic events were similar across groups. Similar findings were observed in the subset of patients with hand NJSA (n=99); only 15 cases of knee or hip infection were included in the entire trial, so subanalysis was not feasible - and the conclusions of the trial are probably not generalizable to those infections.
In my mind, this study tells us two things. First, oral antimicrobial therapy can be adequate for NJSA - in this case, 98% of patients received either all-oral therapy or stepdown to oral therapy after a median 1-2 days of IV antibiotics, and the remission rate was still comfortably >95%. Second, two weeks is clearly as good as four weeks for small joint septic arthritis (i.e. NJSA of the hand). For NJSA involving the knee or hip, the paper really doesn’t enroll enough such subjects to have its conclusions generalized that far, and so I think it’s left an open question.
And with all that out of the way, here are this month’s articles:
Antimicrobial agents research in April covered long-acting glycopeptides for osteomyelitis, rifampin dosing (and possibly a need for infection-specific breakpoints?) in TB meningitis, minocycline repurposed for pulmonary MAC, and the potential of lactoferrin as an adjunctive treatement for H. pyoli
ID diagnostics research in April discussed the role of urinary stone and stent cultures in postprocedural urinary sepsis, albumin as a marker of mortality in septic older adults, blood culture time to positive as a prognostic factor in S. aureus bacteremia (SAB), and the value of FDG-PET in endovascular infections
General ID topics this month included the efficacy and safety of DAA regimens for HCV, treating HCV improves diabetes, retrospective data on whether small vs large joint septic arthritis has different outcomes, mortality in SAB based on duration of culture positivity, and the role of viral coinfections in blunting children’s response to vaccines.
HIV and STD research includes complera for PEP, STIs as a marker of HIV acquisition risk, M. genitalium as a cause of urethritis but not proctitis in MSM, and a modeling study of the benefits of dolutegravir vs efavirenz for women of reproductive potential in the developing world.
Onc and transplant ID research includes a clinical scoring system for invasive fungal infection risk, tularemia as an transplant-associated infection, and macrolides as a potential adjunctive therapy for cryptococcal infections
Antimicrobial stewardship and infection control literature this month included the rise of clindamycin-resistant MRSA in surgical site infections, improvements in adherence to best practice care with a prospective audit and feedback system for SAB, and the efficacy of FMT for recurrent and refractory CDI in randomized clinical trials.