Polymeric nanofiber coating with tunable combinatorial antibiotic delivery prevents biofilm-associated infection in vivo.

Bacterial biofilm formation is a major complication of implantable medical devices that results in therapeutically challenging chronic infections, especially in cases involving antibiotic-resistant bacteria. As an approach to prevent these infections, an electrospun composite coating comprised of poly(lactic-coglycolic acid) (PLGA) nanofibers embedded in a poly(ε-caprolactone) (PCL) film was developed to locally codeliver combinatorial antibiotics from the implant surface. The release of each antibiotic could be adjusted by loading each drug into the different polymers or by varying PLGA:PCL polymer ratios. In a mouse model of biofilm-associated orthopedic-implant infection, three different combinations of antibiotic-loaded coatings were highly effective in preventing infection of the bone/joint tissue and implant biofilm formation and were biocompatible with enhanced osseointegration. This nanofiber composite-coating technology could be used to tailor the delivery of combinatorial antimicrobial agents from various metallic implantable devices or prostheses to effectively decrease biofilm-associated infections in patients.

Safe Parameters for Utilizing Magnetic Growth Rods in Patient With a Vagal Nerve Stimulator and Case Report.

BACKGROUND: Magnetic growing rods are being utilized more frequently in children with early-onset scoliosis. Many of these children have multiple medical problems and additional medical devices implanted that utilize similar magnetic technology, including vagal nerve stimulator (VNS) devices. There is some concern that the external remote controller (ERC) used to control the magnetic growth rod will interact with these devices during lengthening procedures. We believe there are safe parameters which allow the magnetic growth rod ERC to be utilized in patients with an implanted VNS. METHODS: A VNS device was tested in a simulation with the magnetic growth rods ERC to determine if it would activate/inactivate the device during a lengthening procedure. This study consists of 2 simulations. Simulation 1 evaluates placing the VNS adjacent to the ERC in the same coronal plane. Simulation 2 elevates the ERC placement above the device to simulate the thickness of a torso while increasing the distance of the VNS from the ERC in the coronal plane. RESULTS: The time of exposure of the VNS device to the magnetic field had no correlation with activation. Distance had an effect on device activation. In the coronal plane of the device, activation occurred 43% of the time at 0 cm, 71% at 4 cm, and 5% activation at 8 cm. Greater than 10 cm had no activation. In the sagittal plane with the ERC 8 cm above the device, activation occurred 71% at 0 cm distance, 38% at 2 cm, and no activation occurred at a distance of >4 cm. CONCLUSIONS: Utilization of the magnetic growth rod ERC can be carried out safely in patients with a VNS. Simulations show that an actuator implanted 4 cm from the VNS device in the coronal plane in a child with >8 cm chest wall thickness will not activate the VNS device. When choosing a rod configuration for implantation, the child's chest wall thickness and the ERC placement should be considered.

Combination prophylactic therapy with rifampin increases efficacy against an experimental Staphylococcus epidermidis subcutaneous implant-related infection.

The incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low- and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing device-related infections in clinical practice.

Vancomycin-rifampin combination therapy has enhanced efficacy against an experimental Staphylococcus aureus prosthetic joint infection.

Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.

Range of motion measurements in hand surgery: should they be used for assessing outcomes?

PURPOSE: The purpose of the study was to assess how context influences range of motion measurements in hand surgery. METHODS: One hundred seventy-five consecutive patients presenting to a hand surgery clinic were evaluated over 7 sessions. Passive and active motion were measured with a goniometer and by visual estimation. The affected joint was measured by 3 different examiners-one hand surgeon and 2 research assistants (RAs). Measurements by the RAs were performed under the pretense of imaginary project titles and purposes. RESULTS: Range of motion measurements were easily influenced. As the invented project's purpose became more specific and dependent on physician intervention, the bias became more pronounced. Measurements performed under construed project titles that promoted surgical intervention garnered outcomes that supported surgery (P < 0.01). Conversely, when the manufactured study's intent was to find support in conservative treatment, this outcome could also be generated (P < 0.01). DISCUSSION: Range of motion measurements can easily be influenced by the context of the study, even in seemingly blinded examiners. Reliable range of motion measurements can only be made when the examiner has no knowledge of the study's intent.

Daptomycin and tigecycline have broader effective dose ranges than vancomycin as prophylaxis against a Staphylococcus aureus surgical implant infection in mice.

Vancomycin is widely used for intravenous prophylaxis against surgical implant infections. However, it is unclear whether alternative antibiotics used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections are effective as prophylactic agents. The aim of this study was to compare the efficacies of vancomycin, daptomycin, and tigecycline as prophylactic therapy against a methicillin-sensitive S. aureus (MSSA) or MRSA surgical implant infection in mice. MSSA or MRSA was inoculated into the knee joints of mice in the presence of a surgically placed medical-grade metallic implant. The efficacies of low- versus high-dose vancomycin (10 versus 110 mg/kg), daptomycin (1 versus 10 mg/kg), and tigecycline (1 versus 10 mg/kg) intravenous prophylaxis were compared using in vivo bioluminescence imaging, ex vivo bacterial counts, and biofilm formation. High-dose vancomycin, daptomycin, and tigecycline resulted in similar reductions in bacterial burden and biofilm formation. In contrast, low-dose daptomycin and tigecycline were more effective than low-dose vancomycin against the implant infection. In this mouse model of surgical implant MSSA or MRSA infection, daptomycin and tigecycline prophylaxis were effective over a broader dosage range than vancomycin. Future studies in humans will be required to determine whether these broader effective dose ranges for daptomycin and tigecycline in mice translate to improved efficacy in preventing surgical implant infections in clinical practice.

Risk factors for antimicrobial resistance among Staphylococcus isolated from pets living with a patient diagnosed with methicillin-resistant Staphylococcus aureus infection.

It has been suggested that pets play a critical role in the maintenance of methicillin-resistant (MR) and multidrug-resistant (MDR) Staphylococcus spp. in the household. We examined risk factors for carriage of antimicrobial-resistant coagulase-positive staphylococci, with particular attention to Staphylococcus aureus and Staphylococcus pseudintermedius isolated from pets living in households of people diagnosed with methicillin-resistant S. aureus (MRSA) skin or soft-tissue infection. We analyzed data collected cross-sectionally from a study conducted in 2012 that evaluated the transmission of MRSA and other staphylococci from humans, their pets and the environment (Pets and Environmental Transmission of Staphylococci [PETS] study). We used unadjusted and adjusted stratified logistic regression analyses with household-clustered standard errors to evaluate the association between demographic, healthcare-related, contact-related and environmental risk factors and MDR Staphylococcus spp. isolated from dogs and cats. Staphylococcal isolates obtained from dogs (n = 63) and cats (n = 47) were included in these analyses. The use of oral or injectable antimicrobials by the pets during the prior year was the main risk factor of interest. Based on our results, 50% (12/24) of S. aureus, 3.3% (1/30) of S. pseudintermedius and 25% (14/56) of other coagulase-positive staphylococci (CPS) were determined to be MDR. S. aureus isolates were more likely to be MDR compared with S. pseudintermedius. We did not find a significant statistical association between the use of oral or injectable antimicrobials in the prior year and the presence of MDR bacteria. The results suggest that drivers of antimicrobial resistance in household staphylococci may vary by bacterial species, which could have implications for one health intervention strategies for staphylococci and inform the investigation of other reverse zoonoses, such as COVID-19.

Combined in vivo optical and µCT imaging to monitor infection, inflammation, and bone anatomy in an orthopaedic implant infection in mice.

Multimodality imaging has emerged as a common technological approach used in both preclinical and clinical research. Advanced techniques that combine in vivo optical and µCT imaging allow the visualization of biological phenomena in an anatomical context. These imaging modalities may be especially useful to study conditions that impact bone. In particular, orthopaedic implant infections are an important problem in clinical orthopaedic surgery. These infections are difficult to treat because bacterial biofilms form on the foreign surgically implanted materials, leading to persistent inflammation, osteomyelitis and eventual osteolysis of the bone surrounding the implant, which ultimately results in implant loosening and failure. Here, a mouse model of an infected orthopaedic prosthetic implant was used that involved the surgical placement of a Kirschner-wire implant into an intramedullary canal in the femur in such a way that the end of the implant extended into the knee joint. In this model, LysEGFP mice, a mouse strain that has EGFP-fluorescent neutrophils, were employed in conjunction with a bioluminescent Staphylococcus aureus strain, which naturally emits light. The bacteria were inoculated into the knee joints of the mice prior to closing the surgical site. In vivo bioluminescent and fluorescent imaging was used to quantify the bacterial burden and neutrophil inflammatory response, respectively. In addition, µCT imaging was performed on the same mice so that the 3D location of the bioluminescent and fluorescent optical signals could be co-registered with the anatomical µCT images. To quantify the changes in the bone over time, the outer bone volume of the distal femurs were measured at specific time points using a semi-automated contour based segmentation process. Taken together, the combination of in vivo bioluminescent/fluorescent imaging with µCT imaging may be especially useful for the noninvasive monitoring of the infection, inflammatory response and anatomical changes in bone over time.

Does the gatekeeper model work in hand surgery?

BACKGROUND: Most managed care plans use a physician "gatekeeper" to control referrals to hand surgeons. The appropriateness of this model for upper extremity complaints has never been challenged. The purpose of this study was to evaluate the prior management of patients with elective hand disorders who present to a hand surgery clinic. METHODS: All patients presenting to a tertiary, academic medical center for a new-patient hand surgery evaluation from February 3, 2011, to June 15, 2011, were prospectively enrolled. Patients were evaluated for prior provider, diagnosis, treatment, and complications. Actual diagnosis, recommended workup, and appropriate treatment were determined independently by two experienced hand examiners. Traumatic injuries and surgeon disagreements in diagnosis and treatment were excluded, leaving 125 patients. RESULTS: Ninety-eight percent of patients had been evaluated by a primary care provider. Overall, the correct diagnosis was established 34 percent of the time. Nerve compression syndromes were diagnosed with the greatest accuracy (64 percent), whereas stenosing tenosynovitis was diagnosed correctly only 15 percent of the time. Before presentation, 74 percent of patients had undergone a study or intervention. On review, 70 percent of studies/interventions were deemed unnecessary. Advanced imaging was unwarranted in 90 percent of patients who received it. Seventeen percent of patients experienced a complication. Most (67 percent) were caused by a delay in diagnosis, whereas 33 percent resulted from an intervention. CONCLUSIONS: Health care providers less familiar with an examination of the hand often misdiagnose and mistreat common problems. A referral system may not be the most efficient means of delivering care to patients with elective hand maladies.

Allergic dermatitis due to topical antibiotics.

In this report we present a case of allergic dermatitis from chronic use of antibiotic ointment mistakenly diagnosed as a localized finger infection.

Monitoring bacterial burden, inflammation and bone damage longitudinally using optical and µCT imaging in an orthopaedic implant infection in mice.

BACKGROUND: Recent advances in non-invasive optical, radiographic and µCT imaging provide an opportunity to monitor biological processes longitudinally in an anatomical context. One particularly relevant application for combining these modalities is to study orthopaedic implant infections. These infections are characterized by the formation of persistent bacterial biofilms on the implanted materials, causing inflammation, periprosthetic osteolysis, osteomyelitis, and bone damage, resulting in implant loosening and failure. METHODOLOGY/PRINCIPAL FINDINGS: An orthopaedic implant infection model was used in which a titanium Kirshner-wire was surgically placed in femurs of LysEGFP mice, which possess EGFP-fluorescent neutrophils, and a bioluminescent S. aureus strain (Xen29; 1×10(3) CFUs) was inoculated in the knee joint before closure. In vivo bioluminescent, fluorescent, X-ray and µCT imaging were performed on various postoperative days. The bacterial bioluminescent signals of the S. aureus-infected mice peaked on day 19, before decreasing to a basal level of light, which remained measurable for the entire 48 day experiment. Neutrophil EGFP-fluorescent signals of the S. aureus-infected mice were statistically greater than uninfected mice on days 2 and 5, but afterwards the signals for both groups approached background levels of detection. To visualize the three-dimensional location of the bacterial infection and neutrophil infiltration, a diffuse optical tomography reconstruction algorithm was used to co-register the bioluminescent and fluorescent signals with µCT images. To quantify the anatomical bone changes on the µCT images, the outer bone volume of the distal femurs were measured using a semi-automated contour based segmentation process. The outer bone volume increased through day 48, indicating that bone damage continued during the implant infection. CONCLUSIONS/SIGNIFICANCE: Bioluminescent and fluorescent optical imaging was combined with X-ray and µCT imaging to provide noninvasive and longitudinal measurements of the dynamic changes in bacterial burden, neutrophil recruitment and bone damage in a mouse orthopaedic implant infection model.