Kim, Y. S. | Search bioRxiv

bioRxiv2018

Selection of an Appropriate Empiric Antibiotic Regimen in Culture-Negative Hematogenous Vertebral Osteomyelitis

The aim of this study was to determine which antibiotic combinations are appropriate for culture-negative hematogenous vertebral osteomyelitis (HVO), based on the antibiotic-susceptibility pattern of organisms isolated from cases of culture-proven HVO. We conducted a retrospective chart review of adult patients with microbiologically proven HVO in five tertiary-care hospitals over a 7-year period. The appropriateness of empiric antibiotic regimens was assessed based on the antibiotic susceptibility profiles of isolated bacteria. In total, 358 cases of microbiologically proven HVO were identified. The main causative pathogens identified were methicillin-susceptible Staphylococcus aureus (33.5%), followed by methicillin-resistant S. aureus (MRSA) (24.9%), aerobic gram-negative bacteria (21.8%), and Streptococcus species (11.7%). Extended spectrum {beta}-lactamase (ESBL)-producing Enterobacteriaceae and anaerobes accounted for only 1.7% and 1.4%, respectively, of the causative pathogens. Based on the susceptibility results of isolated organisms, levofloxacin plus rifampicin was appropriate in 73.5%, levofloxacin plus clindamycin in 71.2%, and amoxicillin-clavulanate plus ciprofloxacin in 64.5% of cases. These oral combinations were more appropriate for treating community-acquired HVO (85.8%, 84.0%, and 80.4%, respectively) than healthcare-associated HVO (52.6%, 49.6%, and 37.6%, respectively). Vancomycin combined with ciprofloxacin, ceftriaxone, ceftazidime, or cefepime was similarly appropriate (susceptibility rates of 93.0%, 94.1%, 95.8%, and 95.8%, respectively). In conclusion, in a setting with a high prevalence of MRSA HVO, oral antibiotic combinations may be suboptimal for treatment of culture-negative HVO and should be used only in patients with community-acquired HVO. Vancomycin combined with fluoroquinolone or a broad-spectrum cephalosporin was appropriate in most cases of HVO in this study.

epidemiology↗

bioRxiv2017

In vivo calcium imaging visualizes peripheral neuron sensitization in murine osteoarthritis

ObjectiveThe purpose of this study was to develop a method for analyzing sensory neuron responses to mechanical stimuli in vivo, and to evaluate whether these neuronal responses change after destabilization of the medial meniscus (DMM).\n\nMethodsDMM or sham surgery was performed in 10-week old male C57BL/6 wild-type or Pirt-GCaMP3+/- mice. All experiments were performed eight weeks after surgery. Knee and hind paw hyperalgesia were assessed in wild-type mice. The retrograde label DiI was injected into the ipsilateral knee to quantify the number of knee-innervating neurons in the L4 dorsal root ganglion (DRG) in wild-type mice. In vivo calcium imaging was performed on the ipsilateral L4 DRG of Pirt-GCaMP3+/- mice as mechanical stimuli (paw pinch, knee pinch, knee twist) were applied to the ipsilateral hind limb.\n\nResultsEight weeks after surgery, DMM mice had more hyperalgesia in the knee and hind paw compared to sham mice. Intra-articular injection of DiI labeled similar numbers of neurons in the L4 DRG of sham and DMM mice. Increased numbers of sensory neurons responded to all three mechanical stimuli in DMM mice, as assessed by in vivo calcium imaging. The majority of responses in sham and DMM mice were in small-to-medium-sized neurons, consistent with the size of nociceptors. The magnitude of responses was similar between sham and DMM mice.\n\nConclusionsWe demonstrated that increased numbers of small-to-medium sized DRG neurons respond to mechanical stimuli 8 weeks after DMM surgery, suggesting that nociceptors have become sensitized by lowering the response threshold.

neuroscience↗